Publications
Cited in Medline, August 5, 1998.
Accid Anal Prev 1998 Sep;30(5):607-616
Department of Social Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
Hip fracture is a major public health problem, but with a potential for prevention. Data from a European multicentre study on hip fracture epidemiology with a case control design, the MEDOS study, were used to describe and analyse circumstances around falls associated with hip fracture. The study includes 2185 fracture cases age > 50 years from 14 centres in southern Europe: Portugal, Spain, France, Italy, Greece and Turkey. Information was collected by a standardized and validated questionnaire translated into six languages and administered by trained interviewers. Circumstances around the fall were categorized according to: (1) place, age group and time of day; (2) functional disability; (3) drug consumption including alcohol; and (4) environmental factors. Possibilities for prevention were also analysed. High risk falls were identified using seven reasonably well-established risk factors, and similarly eight risk factors were used to identify high risk fallers. Selected trains of events were also studied. A pattern of great diversity was found both among the fallers and the environment in which they fell and fractured the hip. Those with more than one factor involved constituted only 14.7% of female and 19.7% of male fractures. A majority of cases were not physically disabled before the fall. A majority (66.5%) fell and fractured their hip indoors and only 4.3% outside in darkness. Cardiovascular and cerebrovascular comborbidity were observed with 4.9 and 7.8%, of falls respectively. Falls in a stairway comprised 11% of falls. The correlation between the number of the risk factors of the faller and in the environment was 0.07 and there was no difference between males and females. The pattern of causality behind falls that cause hip fracture and therefore of prevention comprises many sometimes small groups and intricate time sequence. The results suggest that global preventive strategies could presently not be implemented. Instead, the pattern of prevention should include different target groups and be country and site specific. For the high risk group of institutionalized patients prevention can be implemented without delay.
J Intern Med 1998 Mar;243(3):223-232
Skara Health Care Center, Sweden.
OBJECTIVES: To assess the coexistence of hypertension and diabetes, associations with cardiovascular risk factors and the achievement of current treatment goals. DESIGN: A community-based, cross-sectional, observational study. SETTING: Hypertension and diabetes outpatient clinics in primary health care, Skara, Sweden. SUBJECTS: All patients (n = 1116; 488 men, 628 women) who performed an annual follow-up from May 1992 to September 1993. MAIN OUTCOME MEASURES: Hypertension, non-insulin-dependent diabetes mellitus (NIDDM), blood pressure, fasting B-glucose, lipids, HbAlc, body mass index (BMI), waist hip ratio (WHR). RESULTS: Hypertension alone was found in 286 men and 430 women, hypertension and NIDDM combined in 102 men and 102 women, and NIDDM alone in 100 men and 96 women. Taking new cases into account, the proportion of hypertension among NIDDM patients was 57%, and the proportion of NIDDM among hypertensives was 26%. Men and women with both hypertension and NIDDM had a higher systolic blood pressure and women also had a higher diastolic blood pressure (men 168/88 mmHg, women 165/86 mmHg) than those with hypertension alone (men 152/87 mmHg, women 156/82 mmHg) (P < or = 0.001). Cardiovascular risk factors accumulated in patients with both hypertension and NIDDM (triglycerides, BMI and WHR). A diastolic blood pressure < or = 90 mmHg was achieved by 71% men and 84% women with hypertension. HbAlc < 7.5% was attained by 71% men and 70% women with NIDDM. CONCLUSIONS: A considerable coexistence of hypertension and NIDDM was demonstrated. Cardiovascular risk factors clustered in patients with both diseases and their blood pressure was less controlled. These patients thus comprised a clinically defined group at high risk. By current guidelines, control of hypertension and NIDDM seemed appropriate.
J Am Soc Nephrol 1998 May;9(5):842-852
Department of Nephrology, University Hospital, Lund, Sweden.
Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are both frequently associated with antineutrophil cytoplasmic autoantibodies (ANCA). Immunosuppressive treatment has dramatically improved outcome for these patients, but today we have to deal with the problems of relapses, cases refractory to treatment, and long-term side effects of therapy. This study comprises a consecutive series of 123 patients with WG (n=56) or MPA (n=67) with biopsy-confirmed renal involvement, followed up for a median of 55 mo (range, 0.1 to 273.2 mo). ANCA was detected by enzyme-linked immunosorbent assay in 97% of patients. Nearly half of the patients (46%) relapsed. There was no statistically significant difference in overall relapse rate according to type of ANCA. Renal survival was 78% in patients alive at the end of follow-up. Three variables seemed important for renal survival: serum creatinine, the titer of proteinase 3-ANCA measured by capture enzyme-linked immunosorbent assay, and B thrombocyte count, at time of referral. Cancer incidence data were obtained from the population-based South Swedish Regional Tumor Registry. Standardized morbidity ratio was calculated using expected values from the health care region. We found an 11-fold increase in risk for bladder cancer in patients treated with cyclophosphamide for at least 12 mo. Skin carcinoma had the strongest relationship with azathioprine use for at least 12 mo and with corticosteroid therapy for at least 48 mo. In addition, four patients developed myelodysplastic syndrome and five had carcinoma in situ of the skin. Because the therapeutic regimen used today is not efficient enough to prevent relapses and is associated with a host of side effects, of which the risk for cancer is by far the most important, improved therapy and medical care are needed for patients with WG and MPA.
Anticancer Res 1998 Jan;18(1B):667-676
Department of Obstet/Gynecol, Lund University Hospital, Sweden.
Pallents with breast cancer exhibit an increased risk of developing cancer from other organs, a risk that might increase due to tamoxifen treatment. This drug has been found to cause activation of oestrogen receptors, leading to oestrogenic effects on the postmenopausal endometrium. We report follow-up of 94 patients with breast cancer without initial symptoms aged more than 50 years at the time of operation. They were followed-up with vaginal ultrasound at regular intervals and endometrial sampling was performed according to treatment after surgery: tamoxifen, tamoxifen in combination with other regimes and without tamoxifen treatment. A large proportion were investigated prior to treatment. We identified endometrial carcinoma, metastasis of breast carcinoma and histopathological changes in 17/67 (25%) of the patients treated with tamoxifen compared to 1/32 in those not treated with tamoxifen.
Med Decis Making 1998 Apr;18(2):168-177
Center for Health and Social Policy, Odense University, Denmark.
A growing empirical literature has investigated attitudes towards discounting of health benefits with regard to social choices of life-saving and health-improving measures and individuals' time preferences for the management of their own health. In this study, the authors elicited the time preferences of vascular surgeons in the context of management of small abdominal aortic aneurysms, for which the choice between early elective surgery and watchful waiting is not straightforward. They interviewed 25 of a random sample of 30 Swedish vascular surgeons. Considerable variation in the time preferences was found in the choices between watchful waiting and surgical intervention among the otherwise very homogeneous group of surgeons. The discount rates derived ranged from 5.3% to 19.4%. The median discount rate (10.4%) is similar to those usually reported for social choices concerning life-saving measures. The surgeons who were employed in university hospitals had higher discount rates than did their colleagues in county and district hospitals.
Genet Epidemiol 1998;15(2):201-212
Department of Epidemiology and Biostatistics, Rammelkamp Center for Education and Research, Case Western Reserve University, Cleveland, Ohio 44109, USA.
Based on a population-based cohort study, Olsson et al. [1993] found significant evidence for elevated incidence of breast and ovarian cancers among female first-degree relatives of men with breast cancer. Using an extension of logistic regressive models we investigate whether, after allowing for multifactorial familial correlations, single locus segregation could be the cause of the elevated incidence in these families. The logit for a given sib in the class D logistic regressive model depends on the order in which affected sibs occur in a sibship. That makes the model less appropriate for the situation where a polygenic component or a common sibling environment may be present, as well as being computationally cumbersome. In this paper, we propose to use the proportion of siblings in a sibship who are affected to quantify a sibling correlation. That not only relaxes the interchangeability problem but also makes the model computationally efficient. We then use this modified class D logistic regressive model for our segregation analysis. Using the proportion of siblings in a sibship who are affected as a covariate resulted in a significantly higher likelihoods in all the models we investigated. We found evidence for a dominant Mendelian gene leading to early age of onset of breast and/or ovarian cancer. This could either be a germline mutation of BRCA2 or a mutation in a gene different from BRCA2.
BMJ 1998 Mar 7;316(7133):741-745
Swedish Network for Pharmacoepidemiology, Foundation, Malmo University Hospital, Sweden. gunnar.lindberg@nepi.a.se
OBJECTIVE: To investigate possible associations between use of cardiovascular drugs and suicide. DESIGN: Cross sectional ecological study based on rates of use of eight cardiovascular drug groups by outpatients. A population based cohort study including users of drugs to control hypertension. SUBJECTS: The ecological study included 152 of Sweden's 284 municipalities. The cohort study included all inhabitants of one Swedish municipality who during 1988 or 1989 had purchased cardiovascular agents from pharmacies within the municipality. Six hundred and seventeen subjects (18.2%) were classified as users of calcium channel blockers and 2780 (81.8%) as non-users. MAIN OUTCOME MEASURES: Partial correlations (least squares method) between rates of use of cardiovascular drugs and age standardised mortality from suicide in Swedish municipalities. Hazard ratios for risk of suicide with adjustments for difference in age and sex in users of calcium channel blockers compared with users of other hypertensive drugs. RESULTS: Among the Swedish municipalities the use of each cardiovascular drug group except angiotensin converting enzyme inhibitors correlated significantly and positively with suicide rates. After adjustment for the use of other cardiovascular drug groups, as a substitute for the prevalence of cardiovascular morbidity, only the correlation with calcium channel blockers remained significant (r = 0.29, P < 0.001). In the cohort study, five users and four non-users of calcium channel blockers committed suicide during the follow up until the end of 1994. The absolute risk associated with use of calcium channel blockers was 1.1 suicides per 1000 person years. The relative risk, adjusted for differences in age and sex, among users versus non-users was 5.4 (95% confidence interval 1.4 to 20.5). CONCLUSIONS: Use of calcium channel blockers may increase the risk of suicide.
J Clin Oncol 1998 Feb;16(2):397-404
Department of Oncology, University Hospital, Lund, Sweden.
PURPOSE: Recent studies indicate that BRCA1 breast and ovarian tumors may have an advantageous survival. In this population-based study, the survival of carriers of a mutated BRCA1 gene was investigated. PATIENTS AND METHODS: The survival of 71 BRCA1-associated cancer patients (33 breast cancer, seven breast and ovarian cancer, and 31 ovarian cancer patients from 21 families with BRCA1 germline mutations) diagnosed after 1958 was compared with that of a population-based comparison group that consisted of all other invasive breast (n = 28,281) and ovarian (n = 7,011) cancers diagnosed during 1958 to 1995, as well as an age- and stage-matched control group. RESULTS: No apparent survival advantage was found for BRCA1-associated breast cancers upon direct comparison. After adjustment for age and calendar year of diagnosis, survival was equal to or worse than that of the comparison group (hazards ratio [HR], 1.5; 95% confidence interval [CI], 0.9 to 2.4). In comparison with an age- and stage-matched control group, survival again appeared equal or worse (HR, 1.5; 95% CI, 0.6 to 3.7). For BRCA1-associated ovarian cancers, an initial survival advantage was noted that disappeared with time. Due to this time dependency, multivariate analyses cannot adequately be analyzed. Compared with the age- and stage-matched control group, survival again appeared equal or worse (HR, 1.2; 95% CI, 0.5 to 2.8). CONCLUSION: The results suggest that survival for carriers of a BRCA1 mutation may be similar, or worse than, that for breast and ovarian cancer in general. This finding is in accordance with the adverse histopathologic features observed in BRCA1 tumors and underlines the need for surveillance in families that carry a BRCA1 mutation.
Scand J Soc Med 1997 Dec;25(4):249-257
Department of Community Medicine, Lund University, Malmo, Sweden.
The reliability and validity of methods to assess social networks, social support and control were investigated in a population of 12,009 females and males born between 1926 and 1945 (the "Malmo Shoulder and Neck Study"). This study demonstrated an overall reliability with kappa coefficients between 0.70 and 0.47, but the reliability was more varying among females and lower in the youngest age group. The analysis of the construct validity indicated that the different indices measure different aspects of the psychosocial environment, but both theoretical and methodological problems were identified, when the validity of multidimensional concepts are to be determined. The validity of such indices can best be judged by combining quantitative and qualitative methods. Potential validity problems must be kept in mind when these indices are used in epidemiological research. The results from the reliability analysis call for repeated assessments and the sample size must be adjusted vis-a-vis the reliability.
Anticancer Res 1997 Sep;17(5B):3821-3824
Department of Obstetrics/Gynecology, Lund University Hospital, Sweden.
Endometrial thickness as measured by ultrasound during tamoxifen treatment has previously been reported. However, there has not been any study investigating endometrial thickness before treatment and following it at regular intervals during treatment. 90 patients with breast cancer without any gynecological symptoms were followed (aged more than 50 years at the operation of their breast cancer). They were investigated by vaginal ultrasound and a common clinical investigation at our out-care patient department. Adjuvant breast cancer therapy consisted of tamoxifen, tamoxifen after radiotherapy and/or in a few cases cytostatics, cytostatics with or without the addition of radiotherapy, radiotherapy or no further therapy. Patients with receptor positive tumours were given tamoxifen. Their endometrium was already thicker before the start of adjuvant treatment as measured by ultrasound. After 3 months and 12 months we found the endometrium to be significantly thicker in those treated with tamoxifen compared to other treatment groups. After 12 months of tamoxifen treatment 22/32 women had an endometrial thickness of 5 mm or more. The frequency of ovarian cysts also seemed to be affected by therapy. In patients treated with tamoxifen alone or in combination, the frequency of cysts was 5/35 before treatment, 6/37 after 3 months, and 0/32 after one year. The corresponding frequencies for those not treated with tamoxifen were 2/20, 3/11 and 3/23 respectively.
J Bone Joint Surg Br 1997 Sep;79(5):880
Acta Orthop Scand 1997 Jun;68(3):205-206
Anticancer Res 1997 May;17(3C):2297-2302
Department of Obstetrics and Gynecology, University Hospital Lund, Lund University, Sweden.
The aim of the present investigation was to see if alternative histopathological parameters could identify a smaller high risk group than commonly seen using routine histopathological parameters. The material consisted of 150 primary resected patients of FIGO Ia-Ic diagnosed as endometrial carcinoma and 12 cases of atypical hyperplasias which were suspected to contain small areas of carcinoma. The patients were treated from December 1979 to April 1993 at the Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden. Those with deep myometrial invasion (> 50%) were given external radiotherapy (20-30 Gy) postoperatively. The follow-up period ranged from 2.5 to 5 years with 116 patients followed-up for more than 5 years. As no therapy was given before surgery we could investigate histopathologic variables such as degree of differentiation and cytology, number of mitoses per high power field (x 40), nuclear polymorphism, mode of invasion, the extension of myometrial invasion, vessel invasion as well as grade of lymphocyte reaction around the tumour cells. We found the degree of differentiation, vessel invasion, number of mitoses, mode of invasion and cytologic abberation to be significant prognostic parameters. The frequency of deep myometrial invasion (> 50%) was extremly high (51/150 = 33%). However, this usually strong parameter was only significant when comparing stage Ia with Ic. Thus the prognostic capacity of myometrial invasion is diminished in primary hysterectomized patients. In the regression analyses only vascular invasion remained significant. By combining vascular invasion with the degree of differentiation we diminished the high-risk group consisting of candidates for further investigation and treatment. Thus a high risk group consisting of poorly differentiated carcinomas with vascular invasion was constructed comprising 24 of 139 patients with a mortality rate of 60%.
N Engl J Med 1997 Apr 24;336(17):1255-1256
Br J Clin Pharmacol 1997 Apr;43(4):449
Cancer 1997 Jan 1;79(1):69-74
Department of Surgery, Malmo University Hospital, Sweden.
BACKGROUND: The incidence of breast carcinoma is increasing in most populations, whereas mortality caused by this disease is fairly constant. The authors analyzed the incidence of and mortality from invasive breast carcinoma in a population with access to good medical care, into which mammographic screening was introduced in 1976 and adjuvant therapy in 1978. METHODS: In a consecutive series of patients with invasive breast carcinoma from Malmo, 1961-1991, changes in age-adjusted incidence were analyzed and compared with incidence of the disease in the rest of Sweden. Age-adjusted breast carcinoma mortality was studied for the period 1964-1992. RESULTS: The introduction of mammographic screening was associated with an increase in breast carcinoma incidence. This was restricted to the age group that was eligible for screening (age 45-69 years) and to Stage I disease. Between 1977 and 1992, age-adjusted breast carcinoma mortality decreased in Malmo by 43% (95% CI, 26-56%) as compared with 12% (95% CI, 8-16%) in the rest of Sweden. The decrease was statistically significant in both populations and significantly greater in Malmo than in the rest of Sweden (P < 0.001). In Malmo the decrease was seen in two age groups, age 45-69 years and age 70 years and older. In the rest of Sweden the decrease was seen only among women age 70 years and older. In the rest of Sweden the decrease was seen only among women age 70 years and older. There were no changes in incidence or mortality among women younger than 45 years in either population. CONCLUSIONS: Breast carcinoma incidence was strongly related to diagnostic activity, especially mammographic screening. The decrease in mortality occurred in temporal relation to the introduction of screening and adjuvant therapy, making a causal relation likely. The difference in results between Malmo and the rest of Sweden indicates an important role for screening in mortality reduction.
Age Ageing 1996 Nov;25(6):439-442
Department of Community Health Sciences, Lund University, Malmo General Hospital, Sweden.
We examined the apparent value of questions of functional status and mental score in determining the risk of hip fracture from a large retrospective case--control study undertaken in six countries. Of nine questions utilized in 75% of the MEDOS study population, four questions were found to be statistically significant and independently related to the risk of hip fracture. From this an additive score was devised with three points for not being able to wash or dress, six points for not knowing one's age, and ten points for not knowing the day of the week, which gave a gradient of risk of 5.7 when categorized into quartiles. Similar gradients of risk were observed in all countries. A less than perfect score was associated with a specificity of 79% and sensitivity of 46%, comparable to the power of bone mineral density measurements. The risk factor score accounted only partially for the increase in risk associated with dementia, cardiovascular accidents and parkinsonism. We conclude that the steep gradient of risk associated with this simple score should be evaluated prospectively.
Acta Orthop Scand 1996 Oct;67(5):505-507
BMJ 1996 Aug 24;313(7055):457-461
OBJECTIVE: To analyse the association between use of antihypertensive treatment, diastolic blood pressure, and long term incidence of ischaemic cardiac events in elderly men. DESIGN: Population based cohort study. Baseline examination in 1982-3 and follow up for up to 10 years. SETTING: Malmo, Sweden. SUBJECTS: 484 randomly selected men born in 1914 and living in Malmo during 1982. MAIN OUTCOME MEASURES: Observational comparisons of incidence rates and rate and hazard ratios of ischaemic cardiac events (myocardial infarction or death due to chronic ischaemic cardiac disease). RESULTS: The crude incidence rate of ischaemic cardiac events was higher in those subjects who were taking antihypertensive drugs than in those who were not (rate ratio 2.6 (95% confidence interval 1.7 to 3.9)). After adjustment for potential confounders (differences in baseline smoking habits, blood pressure, time since diagnosis of hypertension, ischaemic or other cardiovascular disease, hypercholesterolaemia, hypertriglyceridaemia, diabetes mellitus, obesity, and raised serum creatinine concentration) this rate was reduced but still raised (hazard ratio 1.9 (1.0 to 3.7)). In men with diastolic blood pressure > 90 mm Hg, antihypertensive treatment was associated with a twofold increase in the incidence of ischaemic cardiac events (rate ratio 2.0 (1.1 to 3.6)), which vanished after adjustment for potential confounders (hazard ratio 1.1 (0.5 to 2.6)). In those subjects with diastolic blood pressure < or = 90 mm Hg, antihypertensive treatment was associated with fourfold increase in incidence (rate ratio 3.9 (2.1 to 7.1)), which remained after adjustment for potential confounders (hazard ratio 3.8 (1.3 to 11.0)). CONCLUSION: Antihypertensive treatment may increase the risk of myocardial infarction in elderly men with treated diastolic blood pressures < or = 90 mm Hg.
Lakartidningen 1996 Aug 7;93(32-33):2757
[Article in Swedish]
NEPI (Natverk for lakemedelsepidemiologi), Malmo.
J Epidemiol Community Health 1996 Feb;50(1):33-39
Department of Community Medicine, Lund University, Sweden.
STUDY OBJECTIVE: To test the stress hypothesis by characterising women during their first pregnancy who continue to smoke in early pregnancy in comparison with women who quit smoking, with special reference to psychosocial factors like social network, social support, demands, and control in work and daily life. DESIGN: The study is based on a cohort of primigravidas followed during pregnancy. Data were collected by self administered questionnaires during the pregnant womens' first antenatal visit at about 12 weeks. SETTING: The study was performed in the antenatal clinics in the city of Malmo, Sweden. PARTICIPANTS: The participants were all primigravidas living in the city of Malmo, Sweden, over a one year period, 1991-92. A total of 872 (87.7%) of the 994 invited women agreed to participate. The population of this study on smoking includes all primigravidas who at the time of conception were smoking (n = 404, 46.3%). MAIN RESULTS: At the first antenatal visit (63.6% (n = 257) of the prepregnancy smokers were still smoking (a total smoking prevalence of 29.5%). The pregnant smokers were on average younger and had a lower educational level. The highest relative risk (RR) of continued smoking was found among unmarried women RR 2.7 (95% confidence interval) (1.5, 4.8), women having unplanned pregnancies RR 2.2 (1.2, 4.0) and those with a low social participation RR 1.6 (1.0, 2.7), low instrumental support RR 2.6 (1.2, 6.0), low support from the child's father RR 2.1 (1.0, 4.2) and those exposed to job strain RR = 2.3 (1.1, 4.8). The associations were independent of potential confounders such as age, educational level, nationality, cohabiting status, passive smoking, and previous years of smoking. CONCLUSIONS: This study supports the stress hypothesis. Smoking can be one way women handle stress when demands become too great. In order to reduce smoking among pregnant women, maternity centre resources need to be focused more on women with low psychosocial resources who are at highest risk for continued smoking. It is also important to involve actively the woman's partner or other important people in the woman's social network.
Int J Epidemiol 1996 Feb;25(1):80-85
Department of Community Medicine, Lund University, University hospital MAS, Malmo, Sweden.
BACKGROUND: Obesity has, in a number of studies, been found to correlate to disability and mortality, primarily due to diseases of the circulatory and musculoskeletal systems. In addition, an excess mortality among underweight subjects has been observed in previous studies. METHODS: Five complete birth-year cohorts (1926-1930) of male residents in Malmo (n = 7697) were invited to the survey at the Department of Preventive Medicine, Malmo General Hospital, and 5926 (77%) attended with complete data. Each subject was followed from inclusion, defined by the date of examination, until the end of the calendar year when he turned 58, a total study period of approximately 11 years. Data on about 300 questionnaire items and laboratory tests were determined at the health survey visit. Nationwide Swedish data registers were used for surveillance. RESULTS: Of the participants, 4.7% were underweight, 37.7% overweight, 7.3% obese and 50.3% normal weight; 849 (14.3%) had been granted disability pension at the end of follow-up, 717 after screening. After adjustment for smoking there was a J-shaped relation between body mass index (BMI) and incidence of disability pension, the relative risk ( with the normal group as reference) among underweight men being 1.9. For the overweight subjects it was 1.3 and for the obese 2.8, all differences were significant. Disease of the musculoskeletal and circulatory systems and mental disorders accounted for 67.2% of all main diagnoses resulting in disability pensions during follow-up. A total of 377 (6.4%) men died during follow-up. Diseases of the circulatory system, neoplasms, injury/poisoning and diseases of the respiratory system accounted for 91.8% of the deaths. CONCLUSIONS: Both underweight, overweight and obesity were related to risk of disability pension, with a J-shaped risk relationship.
Acta Oncol 1996;35 Suppl 5:75
Department of Oncology, Sahlgrenska Hospital, Goteborg, Sweden.
Scand J Rheumatol Suppl 1996;103:49-52
Department of Social Medicine, WHO Collaborating Centre for the Epidemiology of Rheumatic Conditions, Huddinge University Hospital, Sweden.
The Mediterranean Osteoporosis Study (MEDOS), a multicentre study on incidence, risk factors, and means of prevention of hip fracture in the Mediterranean region, started in 1986 and involved 14 centres, in Portugal, Spain, France, Italy, Greece, and Turkey. The design includes a case-control study comparing 8,185 individuals in age groups above 50 (2,816 cases and 5,369 controls; two controls per case). Information on falls was only collected for a small fraction of the controls. In a questionnaire including 160 main questions eleven referred to circumstances around the fall. Falls were classified according to a) high risk environment, e.g. occurred in darkness and b) high risk fallers, e.g. confusion, reduced functional ability. There was great variation between centra for a majority of the results. However, 2/3 of fractures happened during daylight. 9% of fractures, same for both males and females, took place in darkness. Females have more indoor fractures than males. Around 15% of fractures took place in connection with going to the toilet. Mental factors play a minor role as reported immediate cause to the fall. Before the fall that caused the hip fracture between 28-84% could get up from a chair without any difficulties. Of the males 0-26% lived alone as against 0-37% or females. Conclusion: The data on circumstances around the fall shows a complex pattern with substantial variation between different cultures, but where a, however, minority took place under risk circumstances that have a clear preventive potential.
Eur J Clin Pharmacol 1996;49(4):261-265
Departments of Community Medicine, Lund University, Malmo, Sweden.
OBJECTIVES: An increased risk of all-cause and cardiovascular mortality in users of anxiolytic-hypnotic drugs (AHD) has been reported, and use of analgesics may be an additional factor. Therefore, we examined the association of AHD and analgesic use, alone and in combination, with all-cause and ischaemic heart disease (IHD) mortality. METHODS: Multivariate 10-year survival analysis in a population based cohort of 500 men born in 1914. Relative risks (RR) were adjusted by relevant confounders (blood pressure, serum cholesterol, diabetes mellitus, smoking habit, high alcohol consumption, history of previous IHD, cancer, and other diseases). RESULTS: The RR of both all-cause and IHD mortality were significantly increased among those using both AHD and analgesics compared to those who took neither of these drugs: RR = 1.8 for all-cause mortality, and RR = 2.7 for IHD mortality. CONCLUSION: Although the number of cases was small, warranting interpretative caution, the current study suggests that the combined use of AHD (mainly benzodiazepines) and analgesics seems to be associated with an increase in all-cause and IHD mortality in elderly men.
Lancet 1995 Jun 3;345(8962):1434
Anticancer Res 1995 May;15(3):1095-1100
Department of Obstetrics and Gynecology, University Hospital, Lund, Sweden.
BACKGROUND: Treatment of endometrial carcinoma has not improved during the last decades, due to the already good results. Such therapy has been a compromise, strong enough to cure some of those in need of harder treatment, but weak enough not to cause too severe side-effects. One way of solving the problem of overtreatment is to identify those in real need of a harder regimen. Generally, the histopathologic picture and the depth of myometrial invasion of the tumour have been used. However, this often means a too large high-risk group, often exceeding 50% of the patients. METHODS: Steroid receptor concentrations and later DNA-measurements have been increasingly used to identify high-risk groups not, however, in combination. In 156 patients with endometrial carcinoma, both estradiol receptor concentration and flow cytometrically estimated DNA content were measured on all patients and the patients were followed-up for over five years. RESULTS: By using the number of DNA-populations (ploidy) we could identify a small high-risk group (28%) with a death frequency of 35%. This small group could be further divided, by using the estradiol receptor concentration, into an extremely small high-high-risk group (11%) consisting of 17 patients of whom 9 died from the disease within 5 years, almost all of the deaths occurring within 2 years. CONCLUSION: Thus histopathology was reduced to merely identifying cancer but DNA- and estradiol receptor measurements in combination could identify an extremely small high-risk group, with almost all deaths occurring within 2 years.
Acta Orthop Scand 1995 Apr;66(2):193-195
Department of Community Medicine, Lund University, Sweden.
Scand J Soc Med 1995 Mar;23(1):17-22
Department of Community Health Sciences, Lund University, Malmo, Sweden.
In this study we investigated the importance of social network and social support systems outside the workplace and workload and psychological job strain in former work for the prevalence of daily neck and low back pain. The study population (n = 621) comprised a random half of all male residents in Malmo, Sweden, born in 1914, of whom 500 (80.5%) participated. Two of the social network and social support indices (social anchorage and availability of material and informational support) were independent of life-style factors (leisure time physical activity, smoking and alcohol consumption) related to daily neck and back pain after retirement (OR = 2.0, 95% CI 1.2-3.4 and OR = 1.7, 95% CI 1.0-2.7, respectively), while the psycho-social and physical factors in former work were not. As no conclusion about the direction of the association can be drawn, prospective studies are needed to further explore these findings.
Cancer Detect Prev 1995;19(6):487-493
Department of Community Health Sciences, Lund University, Malmo General Hospital, Sweden.
A case-control study of 177 premenopausal and 216 postmenopausal breast cancer patients diagnosed in the southern Swedish Health Care Region between 1981 and 1984, and 195 premenopausal and 254 postmenopausal controls randomly chosen during 1984 from the same population by means of a computerized population register was used to estimate the relations among alcohol consumption, cigarette smoking, and the risk of cancer. Cigarette smoking did not seem to be related to the risk for breast cancer among pre- or postmenopausal women. Beer consumption did not show any consistent relation to the risk of breast cancer. An occasional (less frequent than once a week) or a weekly consumption of wine and spirits appeared to be protective compared with abstaining (RRadj = 0.4, 95% CI = 0.3-0.7 for weekly wine consumption, and RRadj = 0.6, 95% CI = 0.4-0.9 for occasional consumption of spirits) among postmenopausal but not among premenopausal women (RRadj = 0.8, 95% CI = 0.7-2.3 and RRadj = 1.0, 95% CI = 0.7-1.8 respectively). The risk estimates were adjusted for differences between cases and controls in age at menarche, age at first full-term pregnancy, age at diagnosis, smoking, and use of exogenous hormones, and for postmenopausal women, age at menopause. The study was based on observations of women with a relatively low exposure to cigarette smoking and alcohol. More frequent exposure or exposure to greater quantities of alcohol and smoking may exhibit different relationships with breast cancer risk.
Osteoporos Int 1995;5(6):450-454
Department of Community Health Science, Malmo General Hospital, Lund University, Sweden.
The role of vitamin D in the prevention of hip fracture is controversial and protective effects appear to be confined to the institutionalized and elderly population. The aim of this study was to assess the interaction of age and body mass index (BMI) on the effects of vitamin D on the risk of hip fracture in the community. We studied 1634 women with low-energy fractures of the hip aged 50 years or older, and 3532 age-matched controls from 14 centres in six Mediterranean countries (the MEDOS study), with a structured retrospective questionnaire. The use of vitamin D supplements was associated with a modest and non-significant decrease in the risk of hip fracture (RR = 0.74; 95% confidence interval (CI) 0.53-1.03; p = 0.07). The risk reduction was influenced by age and body mass. Women aged above 80 years had a significant decrease in the relative risk of hip fracture (RR = 0.63; 95% CI 0.40-0.98) as did women with a BMI below 20 kg/m2 (RR = 0.45; 95% CI 0.24-0.84). Elderly women were more likely to have a low BMI but the elderly did not appear to benefit from vitamin D where their BMI was 20 kg/m2 or higher. The findings could not be explained by differences in sun exposure or in physical exercise. We conclude that the use of vitamin D for the prevention of hip fracture might usefully be targeted to the frail and elderly.
Br J Obstet Gynaecol 1994 Jul;101(7):621-625
Department of Obstetrics and Gynaecology, University Hospital, Lund, Sweden.
OBJECTIVE: To compare the prognostic capability of clinical stage, tumour differentiation, myometrial invasion, age and DNA content in endometrial carcinoma. Then to use the results to identify a small, high risk group suitable for more intensive adjuvant therapy. DESIGN: A prospective five year follow up between June 1980 and June 1987. SETTING: Department of Oncology, gynaecological section, University Hospital, Lund, Sweden. Endometrial tissue was obtained immediately prior to treatment for flow cytometric DNA analysis. SUBJECTS: Two hundred and fifty-one patients referred for treatment. INTERVENTIONS: None. RESULTS: Age, myometrial invasion of greater than 50%, and number of DNA populations (ploidy) were the only significant parameters related to survival. By combining myometrial invasion and number of DNA populations, we divided the patients into four groups. A very small high risk group was identified (7%) with a low survival rate (61%). Two intermediate groups with either myometrial invasion exceeding 50% or with more than one DNA population present constituted 34% of the patients and these had an overall survival rate of 75% and a relatively large low risk group of 59% of the patients (with a survival rate of 95%) was constructed out of those without deep myometrial invasion and demonstrating only one DNA population. CONCLUSIONS: These data suggest that number of DNA populations and depth of myometrial invasion could be combined to identify a small high risk group (7%) with a low survival rate (61%) suitable for adjuvant therapy.
BMJ 1994 Mar 12;308(6930):681-686
Department of Community Health Sciences, Lund University, Malmo, Sweden.
OBJECTIVE--To analyse the relation between treated blood pressure and concomitant risk factor and morbidity from acute myocardial infarction. DESIGN--Prospective longitudinal study. Treated blood pressures and other variables were used to predict acute myocardial infarction. SETTING--Primary health care in Skaraborg, Sweden. SUBJECTS--1121 men and 1453 women aged 40-69 years at registration at outpatient clinics, 1977-81, with no evidence of previous myocardial infarction were followed up for an average of 7.4 years. Subjects were undergoing treatment with drugs to lower blood pressure or had blood pressure that exceeded the systolic or diastolic limits, or both, for diagnosis (> 170/> 105 mm Hg (patients aged 40-60 years) and > 180/> 110 mm Hg (older than 60 years)) on three different occasions, or both. MAIN OUTCOME MEASURES--First validated event of fatal or non-fatal acute myocardial infarction. RESULTS--In men but not in women there was a negative relation between treated diastolic blood pressure and risk of acute myocardial infarction. Left ventricular hypertrophy and smoking were contributory risk factors in both sexes, as was serum cholesterol concentration in men. In men with normal electrocardiograms (n = 345) risk increased with increasing diastolic blood pressure (P = 0.047), whereas the opposite was found in men with electrocardiograms suggesting ischaemia or hypertrophy, or both (n = 499, P = 0.009). In those with a reading of 95-99 mm Hg the relative risk was 0.30 (P = 0.034); at > or = 100 mm Hg it was 0.37 (P = 0.027). No similar relations were seen in women or for systolic blood pressure. CONCLUSION--It may be hazardous to lower diastolic blood pressure below 95 mm Hg in hypertensive men with possible ischaemia or hypertrophy, or both. Electrocardiographic findings should be considered when treatment goals are decided for men with hypertension.
Cancer 1994 Mar 1;73(5):1438-1448
Department of Surgery, Malmo General Hospital, University of Lund, Sweden.
BACKGROUND. In a study of 2290 cases of invasive breast cancer in Malmo, the prognostic value of histologic typing and axillary nodal status was examined. Two periods were studied: Period 1, 1961-1970, and Period 2, 1981-1988. METHODS. All primarily unilateral invasive breast cancers were included in the study and classified according to the histologic classification proposed by Linell et al. and Linell and Ljungberg (the Linell-Ljungberg classification), which includes a histologic grading of ductal carcinoma based on content of tubular structures. From Period 1, the tumors were reclassified. In Period 2, the Linell-Ljungberg classification was used as a clinical routine. Median follow-up in Period 1 was 23 years, and in Period 2, 5 years. Survival was calculated in relation to histologic type and axillary nodal status. RESULTS. The Linell-Ljungberg classification divides invasive ductal carcinoma (IDC) into two groups of approximately equal size: IDC of comedo type, 40% of total; and IDC of tubuloductal type, 30% of total. There was a significantly better survival rate in the tubuloductal group than in the comedo group. In a multivariate analysis, this difference was shown to be independent of axillary nodal status and tumor size. By combining histologic classification with axillary nodal status, one group of patients could be identified containing 90% of patients dying from breast cancer within 5 years of diagnosis and another group with less than 10% risk of dying from breast cancer within 5 years. CONCLUSIONS. Valuable prognostic information can be obtained in a clinical setting from routinely obtained primary prognostic factors in breast cancer: pTNM stage, histologic type, and histologic malignancy grade. This information should be considered the baseline in the clinical evaluation of other more elaborate prognostic factors.
Int J Technol Assess Health Care 1994;10(3):498-505
Lund University.
This study describes the operation of an in-home alarm system in seven Swedish municipalities. Statistics on the diffusion of this technology, its costs, and the characteristics of its use are reported. Alarms were triggered by 60% of the users. Mean annual costs per recipient varied from SEK 1,985 to SEK 8,215, mainly reflecting different patterns of use.
Eur J Clin Pharmacol 1994;46(5):393-398
Department of Community Health Sciences, Lund University, Malmo General Hospital, Sweden.
In drug utilisation studies, the units of defined daily doses (DDD) and DDD/1000 inhabitants per day standardise for differences in dosage and population size, but not for age-related differences in drug utilisation. There is no consensus as to how age standardisation of DDD data should be carried out. Using cardiovascular drug utilisation data from Sweden and Spain, the current study compared the outcome of different methods of age standardisation. Both indirect methods (based on a comparison of observed and expected drug usage) and direct methods (using different weighting for the age categories) were used. The largest impact of standardisation was seen for diuretics. The crude rate for men and women combined was 26 DDD/1000 inhabitants per day in Costa de Ponent and 98 DDD/1000 inhabitants per day in Varmland. The corresponding figures when standardising the Costa de Ponent population were 26 and 58, respectively. Using the equivalent average rate (EAR) method, the rate for Varmland was 129 DDD/1000 inhabitants per day. Lesser but still important differences were found for beta-adrenoceptor and antihypertensives. Thus, the results of standardisation differ depending on which method is used and which drugs are evaluated. EAR is recommended for direct standardisation because of its ease of use and because it does not require the choice of a standard population.
Acta Oncol 1994;33(5):557-560
Department of Oncology, Malmo General Hospital, Sweden.
Patients with clinically node negative resectable breast cancer were randomized to either mastectomy only or radical mastectomy and radiotherapy, and followed for 15-20 years. During follow-up axillary metastases occurred with the same frequency after mastectomy as was initially observed in the group that underwent axillary dissection. There was no significant survival difference between the two groups. When adjusting the treatment effect for differences in age, tumour size, lymph node metastases, and histology, the outcome after radical mastectomy plus irradiation was significantly inferior. Comedo carcinoma proved also in this study to carry a poor prognosis.
Eur J Surg 1993 Sep;159(9):461-467
Department of Surgery, Malmo General Hospital, Lund University, Sweden.
OBJECTIVE: To analyse the outcome of selective management of patients with abdominal aortic aneurysms, the expansion patterns of the aneurysms, and the factors that influenced the rate of rupture. DESIGN: Retrospective study. SETTING: Malmo General Hospital, Lund University, Malmo, Sweden. SUBJECTS: 155 patients (96 men and 59 women) with abdominal aortic aneurysms who were not selected for operation for whatever reason were included in the study immediately after their first ultrasound scan. MAIN OUTCOME MEASURES: Mortality, expansion rate (mm/year) measured on ultrasound scan, and rate of rupture of aneurysm. RESULTS: Median aneurysmal diameter was 40 mm (range 20-80), and length (n = 106) 70 (range 28-140). The patients were followed up for a median of 3.4 years (range 0-10.2). A total of 107 patients died and in 21 the aneurysms ruptured (4 were operated on and survived). Thirteen patients were re-evaluated and operated on electively. Ultrasonography was repeated in 98 patients, the median expansion rates (mm/year) were 3.1 (diameter) and 1.9 (length). There was a significant linear relationship between initial size (diameter and length) and rate of expansion of diameter. The risk of rupture was greater in larger aneurysms that were expanding more quickly. The cumulative mortality was not affected by the 21 aneurysms that ruptured. CONCLUSION: Selective management of patients with aortic aneurysms is justified.
Anticancer Res 1993 Jul;13(4):1187-1196
Department of Pathology, University Hospital, Lund, Sweden.
In a prospective study comprising 310 consecutive patients with carcinoma of the cervix, FIGO stages I-IV, the prognostic significance of clinical and flow cytometric variable was evaluated in a univariate and multivariate analysis. The parameters studied included stage according to FIGO, age, histopathologic grade according to Ackerman and MGS scores, DNA ploidy, S-phase fraction as well as treatment with radiation only, surgery only or a combination thereof as well as adjuvant chemotherapy. Univariate analysis showed that patients in FIGO stages IA-IIA with MGS up to 14 points survived significantly better than other groups. MGS parameter mitosis, vascular invasion and type of invasion predicted survival as did clinical stage. Diploid cases with SPF > 15% survived less than remaining other cases. Multivariate analysis not including treatment indicated that FIGO stage and diploid cases with SPF > 15% predicted survival but not total MGS score and age. When treatment for FIGO stages IA-IIA was included, elderly women had a worse prognosis. Adjuvant chemotherapy, surgical alone or radiation alone did not demonstrate any differences within groups. In Figo stages IIB-IV, cases with radiotherapy only survived significantly better than patients with other treatment schedules. The frequency of low malignancy patients (< MGS 16) in relation to year of initial diagnosis was found to have decreased between years 1967 and 1988, probably as a result of screening activities.
Scand J Soc Med 1993 Mar;21(1):3-9
Department of Community Health Sciences, University of Lund, Malmo, Sweden.
In the evaluation of a hypertension treatment program, the end-point surveillance included incidence of acute myocardial infarction and acute stroke identified from hospital in-patient registers and the national mortality register. To ascertain the validity, in-patient records containing the ICD-codes 410-411 and 430-438 were validated. First event of acute myocardial infarction and acute stroke suggested in the in-patient register could be confirmed in 96% and 94%, respectively. In-patient diagnoses of suspected acute myocardial infarction or other acute or subacute ischemic heart diseases, transient ischemic attack and unspecified heart diseases, transient ischemic attack and unspecified cerebrovascular disease revealed high proportions of what in fact turned out to be definite events (11%, 24% and 53% respectively). It is concluded that disease ascertainment for this cohort study claims validation of register data with hospital records.
Eur Heart J 1993 Mar;14(3):291-296
Department of Community Health Sciences, University of Lund, Malmo, Sweden.
The Skaraborg Hypertension Project was undertaken in 1977-1981, and 1428 male and 1812 female hypertensives aged 40-69 years were involved at hypertension out-patient clinics in primary health care. Their long-term risk of acute myocardial infarction during a follow-up of 8.3 years was compared to that of age- and sex-matched controls drawn from the census register at the beginning of surveillance and to normotensive untreated controls identified in a population survey in 1977. Relative risks (with a 95% confidence interval) for acute myocardial infarction morbidity compared to the population was 0.99 (0.78, 1.25) in men and 1.36 (0.95, 1.94) in women. Corresponding figures for acute myocardial infarction mortality were 0.97 (0.68, 1.38) and 1.15 (0.67, 1.99). With normotensive controls used as reference and adjusting for smoking habits and body mass index, the relative risks for acute myocardial infarction morbidity were 1.48 (1.12, 1.98) in men and 2.34 (1.43, 3.85) in women, and for acute myocardial infarction mortality 1.66 (1.07, 2.57) and 1.71 (0.84, 3.48), respectively. Treated hypertension is a weak risk factor for acute myocardial infarction in unselected hypertensive patients.
J Epidemiol Community Health 1993 Feb;47(1):32-35
Department of Community Health Sciences, Lund University, Malmo General Hospital, Sweden.
STUDY OBJECTIVE--The aim was to survey oral contraceptive usage among women under 25 years of age. DESIGN--This was a cross sectional population study based on information collected by questionnaire mailed to randomly selected individuals. SETTING--The study population consisted of Swedish women born between 1960 and 1964 and living in the southern Swedish health care region which has about one and a half million inhabitants. PARTICIPANTS--The sample consisted of 3477 women, of whom 2573 or 74% agreed to participate in the study and were interviewed between November 1990 and April 1991. MAIN RESULTS--Of the 2573 women participating, 2254 (88%) reported having used oral contraceptives at some time, 77% of them having started during their teens. Teenage start of oral contraceptive use was found to be related to a lower age at menarche, a higher marriage/cohabitation rate, a lower rate of teenage full term pregnancy, a higher rate of spontaneous abortion, a lower frequency of teetotalism, and a higher frequency of smoking. Longterm use of antipsychotic drugs appeared to be less common among women who started oral contraceptive use early, but no relationship with other pharmaceutical drug usage was found. No relationship was found between oral contraceptive use and the presence of a first degree relative with cancer. CONCLUSIONS--A large proportion of Swedish women start using oral contraceptives during their teens, and report long duration of usage both before their first full term pregnancy and before the age of 25 years. The few women who have never used oral contraceptives do not appear to be representative of the general population.
J Intern Med 1993 Feb;233(2):155-163
Department of Community Health Sciences, University of Lund, Malmo, Sweden.
Stroke incidence was analysed in a Swedish cohort of male (n = 1428) and female (n = 1812) hypertensive patients in comparison with age- and sex-matched population controls (1:1) and with normotensive untreated subjects (1249 men and 1247 women). Mean follow-up was 8.3 years. Patients were aged 40-69 at the start of follow-up in 1977-1981. Relative risks (95% confidence interval [CI]) for stroke morbidity were 1.63 (1.16, 2.29) for men and 1.40 (0.94, 2.09) for women compared to population controls. Corresponding figures for stroke mortality were 1.96 (1.01-3.82) and 1.48 (0.71-3.06). Compared to the normotensive sample with adjustment for smoking and body mass index relative risks for stroke morbidity were 3.07 (1.96-4.80) for men and 2.56 (1.46-4.51) for women. The prognosis of treated hypertension with respect to stroke is better than anticipated from previous studies, a fact that should be considered when treatment guidelines are developed.
Bone 1993;14 Suppl 1:S73-S75
Centre Viggo Petersen, Paris, France.
The risk of hip fracture is higher among persons living in long-term care than among persons living at home. The aim of this study was to explain the difference in risk between the two types of residence by identifying differences in the respective risk factor profiles. Information from the Mediterranean osteoporosis (MEDOS) study questionnaire was used for statistical analyses of 107 non-demented female cases and 225 neighbourhood controls matched for age, sex, and residential area. The statistical analyses incorporated adjustments of the risk estimates by unconditional multivariate logistic regression. Urban background, activity, and morbidity were found to differ between the two types of residence. The detected differences in risk factor profiles were, however, not considered to be sufficient as an explanation for the difference in risk of fracture.
Gynecol Oncol 1992 Jul;46(1):37-41
Department of Oncology, University Hospital, Lund, Sweden.
During a 9-year period, 92 women with squamous cell carcinoma of the cervix, FIGO stages IA1-IIA, were subjected to primary surgery according to Wertheim Meigs. Grading according to a malignancy grading score (MGS) and evaluation of tumor size before surgery together with surgical findings of positive nodes or insufficient surgical margin at the primary site were used to identify persons prospectively at high risk for relapse. Twenty-five women thus received postoperative treatment. Results among node-positive patients were good; only 2 out of 12 patients relapsed. Among 67 node-negative patients in stages IA2-IIA, 4 relapses occurred. These 4 patients had greater than or equal to 16 risk points according to MGS, but small tumors. Instead of tumor size, supplementary risk factor is therefore needed. Among the few patients in stage IA1, no high-point patients relapsed. These patients would probably have done just as well with less-extensive surgery.
Anticancer Res 1991 Nov;11(6):2043-2046
Department of Community Health Sciences, Malmo General Hospital, Sweden.
In general, findings in studies on oral contraceptives (OCs) and breast cancer have not indicated prognosis to be worse among users of OCs. In few studies, however, has age at the start of OC usage been considered as a prognostic factor. In the present study, prognosis in breast cancer is compared with OC usage, particularly with age at the start of OC usage, among 193 consecutive patients at the Department of Oncology, University Hospital, Lund. An earlier series of 193 breast cancer patients at Malmo General Hospital is included for comparisons. In the Lund series, five-year survival was 62% among women who started to use OCs before the age of 20.78% among those who started to use OCs between the ages of 20 and 25, and 86% among non-users and those who started to use OCs after the age of 25 (p = 0.009, test for homogeneity). Although age was found to be a prognostic factor in the Lund series (RR = 0.90, p = 0.001), this was not so in the earlier (older) Malmo series. The relationship with age differed significantly between the two series (p = 0.003), suggesting the apparent effect of age at diagnosis to be a cohort effect due to the introduction of OCs during the 'sixties. The age-specific relationship between survival and OC usage would seem to indicate the presence of a biological mechanism in which OCs may participate during precancerous and early stages of breast cancer.
J Natl Cancer Inst 1991 Oct 16;83(20):1483-1487
Department of Oncology, University Hospital, Lund, Sweden.
In previous studies in southern Sweden, early use of oral contraceptives has been found to be accompanied by an increased risk of developing premenopausal breast cancer, and the tumors developing in these patients have shown a more aggressive behavior. In the present study, amplification of the proto-oncogenes Her-2/neu (also known as ERBB2) and INT2 was studied in primary tumor specimens from 72 premenopausal women and was related to starting age of oral contraceptive use and other reproductive risk factors. Amplification of Her-2/neu was more common among early oral contraceptive users (i.e., those starting at less than or equal to 20 years of age) than among nonusers or late users (odds ratio [OR], 5.3; 95% confidence interval [CI], 1.6-16.7), whereas INT2 amplification did not differ significantly among those groups (OR, 0.9; 95% CI, 0.1-5.0). The likelihood of INT2 amplification was greater among users of progestins and those with a history of abortions before the first full-term pregnancy (OR, 9.0; 95% CI, 1.3-51.7; and OR, 18.6; 95% CI, 2.2-165.8, respectively). No significant relationships were found between proto-oncogene amplification and the variables of parity, age at first full-term pregnancy, or late abortion. The increased ORs persisted after adjustment for age at diagnosis and other risk factors. The findings suggest that the higher rate of Her-2/neu amplification among early oral contraceptive users is an effect of the oral contraceptive use per se rather than of the relative youth of the users. Moreover, the relationship between progestin use and early abortion and amplification of the INT2 gene is biologically plausible.
In Vivo 1991 Jul;5(4):401-406
Department of Oncology, University Hospital, Lund, Sweden.
To study the importance of estrogen availability to growth pattern and other tumor characteristic such as estrogen receptor (ER) and progesterone receptor (PgR) content and histopathology, we have used a human tumor-nude mouse model, in which an ER- and PgR-positive and estradiol-sensitive (stimulated) human endometrial adenocarcinoma was heterotransplanted and serially passed in female (non-oophorectomized) nude mice over a period of one year. Pieces from this tumor were transplanted into oophorectomized nude mice, randomly divided into two groups, one with and one without estradiol treatment (preparation phase). After four weeks, pieces from both these groups were again transplanted into oophorectomized nude mice, each group being randomly allocated to two subgroups, one with and one without estradiol treatment (experimental phase). Tumor growth was measured during the experimental phase, whereas both ER and PgR content and histopathology were analyzed after the experimental phase. Our findings indicate that even short-term growth under estradiol-poor conditions can trigger such progressive changes as reduced steroid receptor content, development of a less differentiated tumor and tendency to enhanced tumor growth. On the other hand, estradiol-rich conditions enhanced ER activation, PgR induction and tumor differentiation in the same tumor line. The estrogenic conditions under which a tumor grows may thus be crucial determinants of tumor progression.
Scanning Microsc 1991 Jun;5(2):573-582
Department of Oncology, University Hospital, Lund, Sweden.
The ciliated epithelium of the rabbit trachea was irradiated with daily fractions of 2 Gy up to an accumulated dose of 20 Gy (total dose: 2, 6, 10, 16, or 20 Gy). Fifteen to forty-five minutes before the start of each irradiation 0.3 mg Cis-diamminedichloroplatinum (cis-DDP) was given by intraperitoneal injection to each rabbit. Examinations were carried out 1-10 days after each fractionation schedule, when specimens were taken for morphological investigations. Scanning electron microscope (SEM) examination showed a gradual development of ciliary damage, from blebs on the cilia to swollen tips, broken and bent cilia and finally an epithelial injury with areas free from cilia, and a surface covered with microvilli-like structures. SEM also showed cell loss, and remnants of dead cells on the surface together with detritus. By transmission electron microscopy (TEM), ciliary damage, cell death and cell loss of the ciliated cell layer, as well as exfoliation of portions of goblet-like cells on the surface, could be confirmed. Scoring of SEM and TEM micrographs showed that for the tracheal part treated with cis-DDP and radiation, the maximal damage was expressed in the dose group 10 Gy, and above this no further increase in the average reaction occurred. For the part of the trachea only exposed to cis-DDP, the damage increased with the dose. The difference observed speaks for an accelerated proliferation exerted by the radiation.
Clin Rheumatol 1991 Mar;10(1):54-72
Arthritis and Metabolic Bone Disease Research Unit, K.U. Leuven, Belgium.
The Mediterranean osteoporosis study (MEDOS) questionnaire was designed by a group of specialists in bone disease from Southern Europe (MAB Group) and the WHO Collaborating Centre for the Epidemiology of Rheumatic Conditions, assisted by experts from WHO in Geneva and from the European Foundation for Osteoporosis and Bone Disease. The purpose of the questionnaire was to identify putative risk factors for hip fracture in a retrospective case control study applied during a prospective study of the incidence of hip fracture in 14 regions of Europe.
Cancer 1991 Mar 1;67(5):1285-1290
Department of Oncology, University Hospital, Lund, Sweden.
In 175 premenopausal breast cancer patients, a history of oral contraceptive (OC) use before 20 years of age was significantly associated with higher tumor cell proliferative activity, as indicated by a higher S-phase fraction (SPF), and a higher fraction of DNA aneuploid tumors, compared with later or never users (P = 0.05 and p = 0.01, respectively). The higher SPF among early OC users was apparent in patients with aneuploid tumors but not in patients with euploid tumors. Abortions (spontaneous or induced) before the first full-term pregnancy also were associated with a higher SPF compared with other young patients with breast cancer (P = 0.03). Adjusting for parity and abortions or OC use, respectively, an early OC use was associated with a 43% higher SPF and early abortions were associated with 49% higher SPF. Younger patients had a higher SPF and a higher frequency of aneuploid tumors, but this was found to be because the users of OC had a lower median age at diagnosis. Among never users, no significant age relationship was seen for SPF or the frequency of aneuploidy. For the DNA analyses there is a selection of patients with breast cancer with larger tumors, and therefore the conclusions drawn in this article may not be generalizable to patients with smaller primary tumors, e.g., cases diagnosed at breast cancer screening. The higher tumor proliferative activity and frequency of aneuploidy in early OC users are in line with previously reported findings of worse prognostic indicators and a worse survival in early users of OC compared with other young women with breast cancer.
In Vivo 1991 Mar;5(2):185-190
Gynecologic Section, University Hospital, Lund, Sweden.
We have used a human tumor nude mouse model involving heterotransplantation and serial passage of an estrogen receptor (ER) positive, progesterone receptor (PgR) negative human endometrial adenocarcinoma. The effects of estradiol treatment on tumor growth, ER activation and PgR induction were investigated two and four years after heterotransplantation. In Experiment I, two years after initial heterotransplantation, tumor growth and proliferative rate showed a dose-related decrease, ER was activated by estradiol treatment (measured through an increased amount of ER bound with high affinity to nuclear element(s) (ERhs) and PgR was induced. Two years later (Experiment II), the amount of ER1s (ER measured in cytosolic fraction) as well as of ERhs was lower than at the beginning of Experiment I. ER could again be activated by estradiol treatment and PgR was also induced. However, in this experiment no effect either of tumor growth or of proliferative rate was observed during the estradiol treatment. Our study therefore indicates that an estrogen non-sensitive growth can develop during serial passages in intact, non-treated female nude mice, although the capacity for ER activation and PgR induction is maintained.
Comput Biomed Res 1991 Feb;24(1):47-57
Department of Mathematical Statistics, University of Lund, Sweden.
The rate of lead elimination in blood by occupationally exposed individuals has been studies using a compartment model with three exponential terms. The analysis of data by exponential regression leads to numerical problems. It is often a difficult task to decide how many measurements should be performed, the length of the observation period, and how the observations should be distributed to get high accuracy. In a simulation study, the sensitivity of the parameter estimates was investigated as a function of these three factors. The effects of missing observations in some interval was also studied. It is shown that a too short observation time leads to a relatively high frequency of outliers in the estimated values of all three half-times. It is also shown that missing values in one compartment affect the parameter estimates of that and faster compartments. The results obtained can be used as a help to decide what experimental accuracy is needed for a given accuracy of compartment model parameters for a variety of medical and biological problems.
Lancet 1991 Jan 26;337(8735):244
Cancer Detect Prev 1991;15(4):265-271
Department of Oncology, University Hospital, Lund, Sweden.
In southern Sweden, extensive oral contraceptive use (OC use) among young women was a reality during the 1960s, thus making our region especially suited for studies investigating the hypothesis that early OC use is associated with the development of premenopausal breast cancer after a possible latency time between the exposure and the disease. The results of this study revealed that the risk of developing premenopausal breast cancer in women, who during the 1960s used the pill as teenagers, is five times greater than nonusers. The risk for early users is further modified by the duration of use at an early age, implying a dose-response relationship. Later use of OCs is not associated with an increased risk for the disease. Women with breast cancer, who at an early age have used the pill, have larger breast tumors, lower estrogen receptor concentrations of their primary tumor, and a worse prognosis compared with later and nonusers with breast cancer. The incidence of breast cancer in Sweden rapidly increased in women 25 to 40 years of age between 1970 and 1984. Conventional risk factors or a change in diagnostic activities of breast cancer cannot explain the increase in incidence which could be due to the OC exposure. Studies on the risk with modern OCs must wait another 20 years because of a too short latency time.
Acta Oncol 1991;30(5):617-622
Department of Oncology, University Hospital, Lund, Sweden.
The combination of cisplatin (90-120 mg/m2) and 5-fluorouracil (5-FU) (1,000 mg/m2/day in continuous infusion for five days) was given for 2-3 cycles, prior to combined radiotherapy and surgery, to 73 patients with esophageal squamous cell carcinoma, 60 with limited disease (LD), and 13 with extensive disease (ED) (i.e. with metastasis) of whom 3 had recurrent disease. Before preoperative radiotherapy among 60 LD patients, 12 (20%) had complete response, 21 (35%) partial response, 25 (42%) had stable disease, and 2 (3%) progressive disease. Swallowing was improved in 35/73 (48%) of the cases. In the resected specimens, no tumor was found in 8/53 (15%) of the cases, microscopic tumor in 18/53 (34%) and macroscopic tumor in 27/53 (51%). In the ED group, complete response of distant metastases was obtained in 6/13 (48%) of the patients, one of whom is still alive with no evidence of disease 62 months after the start of treatment.
Br J Surg 1990 Dec;77(12):1375-1378
Department of Surgery, Lund University, Sweden.
Total gastrectomy and oesophagojejunostomy with linear stapling devices were performed on 22 pigs to evaluate whether intersecting staple lines reduce the blood flow with an increased risk of anastomotic leakage. The blood flow at intersecting staple lines and single row staple lines of the anastomosis was studied with the reference organ method 24 h after the first operation. The mean blood flow in intersecting staple lines was 0.305 ml min-1 g-1 tissue and 0.307 ml min-1 g-1 tissue for single row staple lines. The confidence interval for the reduction in blood flow for intersecting staple lines compared with non-crossing staple lines was from -16 to +17 per cent. In one animal the reduction in blood flow was 37 per cent; in all other animals there was no reduction in blood flow or a reduction less than 25 per cent. An equivalence test shows that if a reduction in blood flow exists it is most likely to be less than 30 per cent (P less than 0.001). Our data confirm that intersecting staple lines in oesophagojejunal anastomoses do not reduce mean anastomotic blood flow to a dangerous level.
J Hypertens 1990 Dec;8(12):1147-1153
Department of Community Health Sciences, Lund University, Malmo, Sweden.
The Skaraborg Hypertension Project is a 5-year trial testing the impact of structured hypertension care implemented in half of the country, the other half serving as control. Population investigations revealed improved blood pressure control in all treated hypertensives in the study area, blood pressure reduction averaging 2-5 mmHg. The primary trial hypothesis of a possible impact on stroke incidence in the community was tested in this study. Cases of fatal and non-fatal stroke were identified from local and national mortality and morbidity registers, and diagnoses were validated against medical records. Of an initial 1169 reported cases, 1097 proved to be true stroke after validation. A statistically significant difference in stroke incidence trends (fatal and non-fatal) between the study and control populations was identified (P = 0.0251). Improved hypertension control in the study area seems the most plausible explanation for the relative decline in stroke incidence in the study area.
Br J Cancer 1990 Nov;62(5):786-790
Department of Oncology, University Hospital, Lund, Sweden.
The use of continuous prognostic variables is clinically impractical, and arbitrarily chosen cut-off points can result in a loss of prognostic information. Here we report findings from a study of primary breast cancer, showing how the prognostic value of the fraction of cells in the S-phase of the cell cycle (SPF), as measured by flow cytometry, can be affected by the SPF cut-off level(s) adopted. It was possible to evaluate the SPF in 566 (94%) of 603 consecutive cases where fresh frozen specimens were available in a tumour bank at our department. Clinically, all patients were without distant spread at the time of diagnosis, and the median duration of follow-up was 4 years. Using different survival end-points and chi 2 values for each cut-off level, two optimal cut-off points, at the 7% and 12% levels, were consistently obtained for the SPF. Furthermore, both disease-free survival and the relative risk of recurrence exhibited a non-linear relationship with SPF values; the curves implied that the prognosis was better among patients with SPF values about 2-5% than in patients with lower SPF values (parabolic shape), though the relationship with higher SPF values approached linearity. The non-linearity of the curves is incompatible with the general use of the median SPF as a prognostic cut-off value. An alternative procedure might be to use two cut-off levels, one to distinguish patients with the lowest SPF values (i.e. within the parabolic survival curve) from those with higher values (i.e. with a survival curve approaching linearity), the other to distinguish between patients with intermediate SPF values and those with high values (i.e. within the almost linear part of the survival curve). The 7% and 12% obtained here would be suitable for this purpose. We conclude that prognostic information can be gained by dividing the SPF into three prognostic categories (less than 7.0%, 7.0-11.9% and greater than or equal to 12%), instead of using the median SPF level.
J Clin Oncol 1990 Mar;8(3):538-547
Department of Oncology, Lund University Hospital, Sweden.
The nuclear DNA content of 148 high-grade soft tissue sarcomas of the extremities and trunk was determined by flow cytometry, using tumor material from paraffin-embedded tissue. The patients were part of a prospective randomized clinical trial on the efficacy of adjuvant single-agent chemotherapy with doxorubicin. Chemotherapy did not improve the metastasis-free survival (MFS). After a median follow-up time of 48 months (range, 2 to 97), a multivariate analysis of prognostic factors for developing metastatic disease was performed. DNA aneuploidy was found to be an independent prognostic risk factor in addition to histologic malignancy grade IV, intratumoral vascular invasion, tumor size over 10 cm, and male sex. Patients with none or one risk factor had a 5-year MFS of 79%, with two risk factors 65%, with three risk factors 43%, and with four and five risk factors 0%. About one half (78 of 148) of the patients with three factors or less belonged to a group with a MFS over 60%. The combination of different risk factors, including DNA aneuploidy, seems to be a useful prognostic model for soft tissue sarcomas, which could be of value to select high-risk patients for further trials with adjunctive therapy.
Int Orthop 1990;14(2):199-204
Department of Orthopaedics, University of Lund, Sweden.
Using the Cox proportional hazards model, and considering tumour necrosis and vascular invasion by tumour as additional factors in assessment, a series of 88 patients with primary Grade III and IV soft tissue sarcomas of the locomotor system was analysed for factors associated with death due to the tumour. Grade IV malignancy, a tumour size larger than 10 cm., tumour necrosis, and vascular invasion by tumour cells were significant risk factors. Patients with 0 or 1 risk factor, one half of the cases, had a 3 year survival rate of more than 90%, whereas the figure was 65% for those with 2 risk factors and 20% for those with 3 or 4 risk factors.
Neoplasma 1990;37(2):185-190
Department of Oncology, University Hospital, Lund, Sweden.
Women with malignant lymphoma, non-Hodgkin's lymphoma and Hodgkin's disease were of a significantly later age at first full-term pregnancy (AFFP) than controls without malignant disorders. The odds ratio (OR) of having the first pregnancy at 30 years of fertility was 6.4 for women with malignant lymphoma. This ratio was higher than the ratio of 3.9 in a group of breast cancer patients. A low parity in the lymphoma group enhanced the risk associated with a late AFFP.
Br J Cancer 1990 Jan;61(1):120-122
Department of Community Health Sciences, Lund University, Malmo General Hospital, Sweden.
The national Swedish cancer registry was used to analyse the age-specific time trends in breast cancer incidence in Sweden from 1970 to 1984. The analysis included both a calendar year and a birth cohort approach to estimate time trends in disease occurrence. According to the birth cohort approach there was a statistically significant increase in the incidence with an average annual increase of the incidence of 3.2% (P = 0.0114), 3.4% (P = 0.0002) and 2.2% (P = 0.0264) in the age groups 25-29, 30-34 and 35-39, respectively. Possible causes of the observed increasing incidence are discussed.
Anticancer Res 1990 Jan;10(1):59-62
Department of Oncology, University Hospital, Lund, Sweden.
Gonadal and hypophyseal hormones were investigated in 15 males with breast cancer and 15 tumour referents, on average 1 month postoperatively. Plasma prolactin was found to be significantly more often elevated in men with breast cancer compared with referents (p less than 0.005). Another group of men with breast cancer disclosed a tendency for lower S-FSH levels compared with the referents (p less than 0.01). No significant difference was seen between cases and referents regarding S-LH, p-estradiol or p-testosterone. The size of the primary breast tumour was correlated with a higher prolactin level. The findings lend support to a theory implicating prolactin and possibly prolactinomas as a risk factor for the disease in males.
Lakartidningen 1989 Dec 20;86(51):4509-4511
[Article in Swedish]
Acta Orthop Scand 1989 Dec;60(6):687-692
Orthopedic Service, Ulleval Hospital, University of Oslo, Norway.
Two-hundred and forty adult patients with a high-grade soft tissue sarcoma were treated surgically in 18 hospitals participating in the Scandinavian Sarcoma Group Protocol I. The patients were randomized to either postoperative doxorubicin or control; patients whose surgical margin was judged marginal also received radiotherapy. The outcome after different surgical margins was analyzed in 185 tumors of Grades III or IV in the extremities. The total cumulative local tumor control was 91 percent (168 of 185) after a median of 47 months. The cumulative local control rates in the surgical groups were: compartmental or wide amputation--37/37 (100 percent), compartmental local excision--23/24 (96 percent), wide local excision--77/84 (92 percent), marginal excision and radiotherapy--19/21 (90 percent), and marginal excision alone (reevaluated margin)--12/19 (63 percent, significantly lower than others). The risk of local recurrence was 13 times higher after marginal than after compartmental surgery (P = 0.02) and 3 times higher if the tumor was larger than 10 cm (P = 0.05). The treatment with doxorubicin did not influence the risk of local recurrence. The survival rates did not differ significantly in the groups.
Acta Orthop Scand 1989 Oct;60(5):517-521
Department of Oncology, Lund University Hospital, Sweden.
From 1981 to 1986, 240 patients with primary, malignancy grade III or IV soft-tissue sarcoma were entered into a randomized adjuvant chemotherapy multicenter trial, conducted by the Scandinavian Sarcoma Group. After a median follow-up time of 46 (2-97) months, a multivariate analysis of risk factors for metastases was performed in 138 radically operated on patients with tumors of the extremities. Adjuvant single-agent doxorubicin did not improve the metastasis-free survival. Histologic malignancy grade IV, tumor size greater than 10 cm, vascular invasion by tumor, and male sex were identified as risk factors. Patients with no or one risk factor had a 5-year metastasis-free survival of 0.7, with two risk factors 0.5, and with three or four risk factors 0.2. The combination of different risk factors provides a prognostic model for soft tissue sarcomas, which could be a basis for therapeutic trials.
J Natl Cancer Inst 1989 Jul 5;81(13):1000-1004
Department of Oncology, University Hospital, Lund, Sweden.
In southern Sweden during the 1960s, women began to use oral contraceptives (OCs) extensively at a young age. This case-control study investigates the relationship between the use of OCs and breast cancer development in women in southern Sweden diagnosed in the early 1980s. The risk for breast cancer after OC use among premenopausal women was modeled, after adjustment was made for age, age at menarche, and age at first full-term pregnancy or parity. Both the duration of OC use before 25 years of age and commencement of OC use at a young age were associated with a significant increase in the risk of breast cancer as well as a significant trend. The duration of OC use before the first full-term pregnancy was associated with an increased risk of breast cancer, but it did not show a significant trend. The total duration of OC use was weakly, but not significantly, associated with breast cancer development. The odds ratio for women starting OC use before 20 years of age was 5.8 [95% confidence interval (CI), 2.6-12.8]; for women using OCs for greater than 5 years before age 25, it was 5.3 (95% CI, 2.1-13.2); and for women using OCs for greater than or equal to 8 years before first full-term pregnancy, it was 2.0 (95% CI, 0.8-4.7). In multivariate analyses including the different measurements of OC use, only starting age of OC use was significantly associated with breast cancer. The exposure-response relationship between duration of OC use and risk of breast cancer depended on the age at first use of OCs. Given a fixed duration of OC use, the risk increased with younger starting age of OC use. The findings point to the importance of the early reproductive years as risk determinants for breast cancer after OC use.
Br J Cancer 1989 May;59(5):834
Lancet 1989 Apr 8;1(8641):783
Lakartidningen 1989 Mar 1;86(9):704
[Article in Swedish]
Anticancer Res 1989 Mar;9(2):487-499
Department of Surgery, University Hospital of Lund, Sweden.
During six years 188 consecutive patients with gastric carcinoma admitted to the Department of Surgery, University Hospital, Lund, were followed up to evaluate clinical as well as histopathologic factors which might be important to predict postoperative survival. We also introduced a new histopathologic scoring system based on nine different parameters. Radicality estimated by the surgeon, resection line margin, score at histologic grading and TNM were factors which in a multivariate analysis strongly correlated to survival.
In Vivo 1989 Mar;3(2):93-97
Gynecologic Section, University Hospital, Lund, Sweden.
The interaction between estradiol and its receptor in human endometrial adenocarcinoma was investigated in a human tumor-nude mice model. Estradiol treatment was found to activate estrogen receptor (ER), estimated through the measurement of ER in the nuclear fraction. The receptor activation in the tumors was significantly higher in tumors previously treated with estradiol than in previously non-treated tumors. The activation seems also to be dependent on the estrogen dose. We concluded, that previous influence of estradiol may change the sensitivity of estrogen receptor positive tumors for its hormone, and therefore the measurement of the receptor content alone does not seem to be a sufficient marker for the prediction of the receptor activation process.
Acta Oncol 1989;28(2):267-270
Department of Oncology, University Hospital Lund, Sweden.
149 patients with carcinoma of the esophagus treated with radiotherapy were evaluated. Eighty-one patients had treatment with palliative intent and 68 with curative intent. The 4-year actuarial survival was 1 and 5% respectively. The tumor size, Karnofsky index (KI) and radiation dose were prognostic factors. The duration of palliation of the patients dysphagia was dose-dependent.
BMJ 1988 Oct 15;297(6654):943-948
Department of Radiology, Malmo General Hospital, Sweden.
STUDY OBJECTIVE--To determine whether mortality from breast cancer could be reduced by repeated mammographic screening. DESIGN--Birth year cohorts of city population separately randomised into study and control groups. SETTING--Screening clinic outside main hospital. PATIENTS--Women aged over 45; 21,088 invited for screening and 21,195 in control group. INTERVENTIONS--Women in the study group were invited to attend for mammographic screening at intervals of 18-24 months. Five rounds of screening were completed. Breast cancer was treated according to stage at diagnosis. END POINT--Mortality from breast cancer. MEASUREMENTS AND MAIN RESULTS--All women were followed up and classed at end point as alive without breast cancer, alive with breast cancer, dead from breast cancer, or dead from other causes. Cause of death was taken from national mortality registry and for patients with breast cancer was validated independently. Mean follow up was 8.8 years. Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer (no significant difference; relative risk 0.96 (95% confidence interval 0.68 to 1.35)). In the study group 29% more women aged less than 55 died of breast cancer (28 v 22; relative risk 1.29 (0.74 to 2.25)). More women in the study group died from breast cancer in the first seven years; after that the trend reversed, especially in women aged greater than or equal to 55 at entry. Overall, women in the study group aged greater than or equal to 55 had a 20% reduction in mortality from breast cancer (35 v 44; relative risk 0.79 (0.51 to 1.24)). OTHER FINDINGS--In the study group 100 (17%) cancers appeared in intervals between screenings and 107 (18%) in non-attenders; 51 of these women died from breast cancer. Cancers classed as stages II-IV comprised 33% (190/579) of cancers in the study group and 52% (231/443) in the control group. CONCLUSIONS--Invitation to mammographic screening may lead to reduced mortality from breast cancer, at least in women aged 55 or over.
Cancer 1988 Sep 1;62(5):895-904
Department of Thoracic Surgery, University Hospital, Lund, Sweden.
Sixty-six patients with squamous cell carcinoma of the esophagus were treated with combined surgery and radiotherapy, mostly in a sandwich fashion. Fourteen patients received misonidazole during preoperative radiotherapy. Prospective cumulative survival at 1, 2, and 5 years was 60%, 35%, and 17%, respectively. Original biopsy specimens and operation specimens were evaluated according to a histopathologic grading system based on an evaluation of the tumor cell population in terms of cell differentiation, structure, nuclear polymorphism, and the frequency of mitotic figures. The tumor-host relationship was also estimated by the mode of invasion, stage of invasion, vascular invasion, and degree of lymphocytic infiltration. A multivariate regression analysis according to Cox and actuarial survival were used to determine the relative contributions of the clinical and histopathologic parameters to patient outcome. The major results were as follows: (1) patients who were old (70 to 80 years) fared as well as younger patients (P = 0.9198); (2) tumor site did not influence therapeutic outcome (P = 0.1100); (3) there was an insignificant difference in survival between patients with M0 and M1 disease (P = 0.7130); (4) radical surgery gave better survival; (5) misonidazole administered preoperatively was associated with worse survival (P = 0.0147); and (6) the histopathologic malignancy grading score system was very useful for prognostication--the tumor-host score in the operative specimen was the strongest of all analyzed predictive parameters. Since palliation was excellent in all patients treated in the combined fashion, selection criteria should be wide for such a program, not the least since long-term survival is possible also for patients with very advanced tumors.
J Natl Cancer Inst 1988 Jul 6;80(9):679-683
Department of Oncology, University Hospital, Lund, Sweden.
On the basis of information obtained from a population-based cancer registry in Sweden, male patients with breast cancer (n = 95) were found to have experienced significantly more brain concussions and skull fractures than male patients with lung cancer (n = 383) or malignant lymphoma (n = 69). Other risk factors significantly associated with breast cancer among men were drug treatment associated with prolactin elevations, radiation treatment, family history of breast cancer among first-degree relatives, a history of gynecomastia, gonadal injury, and treatment for inguinal hernias. The results confirm some previously described risk factors for male breast cancer and suggest that events elevating plasma prolactin (e.g., drugs, brain concussions, and skull fractures) and events predisposing for inguinal hernias may be new risk factors for the disease. Using hospital charts is likely to underestimate exposure for different risk factors; therefore, the results need to be confirmed in studies that directly retrieve information. However, such studies are difficult or impossible to undertake in most countries because the disease is so rare.
Anticancer Res 1988 Jan;8(1):29-32
Department of Oncology, University Hospital, Lund, Sweden.
The survival of 193 premenopausal breast cancer patients was investigated in relation to their history of early use of oral contraceptives. The women were born in 1939 or later and diagnosed in the southern health care region of Sweden. Women, who had started their oral contraceptive use (OC-use) before 20 years of age had a significantly lower survival rate as compared with those who had never used OC and late users (p = 0.02 and = 0.04 respectively, generalized Wilcoxon test). For women who started OC-use between 20 to 25 years of age, a tendency for a shorter survival was seen in comparison with women who had never used OC (p = 0.18). For all patients simultaneously, the relative risk adjusted for age at diagnosis increased for earlier OC-start. When only stages II and III were considered in a stratified multivariate model, a significantly elevated risk was seen for early users of OC irrespective of age or of adjuvant treatment given. The estrogen and progesterone receptor concentrations of the primary tumor were significantly lower among early users (p = 0.001 and p = 0.05 respectively).
Am J Ind Med 1988;14(6):643-647
Department of Occupational Medicine, Malmo General Hospital, Sweden.
Increased volume of trapped gas (VTG) was found in 87 asbestos-exposed railroad repair shop workers, divided into three subgroups according to smoking habits. All the examined subjects had pleural plaques. Determination of VTG was used to study function of small airways. Increased VTG was found among asbestos-exposed smokers as well as nonsmokers. In both groups the VTG:TLC ratio was elevated compared with controls. Increased VTG is a sign of small airways dysfunction. In asbestos-exposed subjects, it might be caused by an early peribronchial reaction to inhaled asbestos fibers.
Am J Ind Med 1988;14(6):635-641
Department of Occupational Medicine, Malmo General Hospital, Sweden.
Eighty-seven workers exposed to asbestos in a railroad car repair shop, with characteristic asbestos-induced pleural plaques, underwent extensive lung-function examination. Vital capacity (VC) showed the greatest reduction among the static lung volumes, with an asymmetrical distribution of one-fourth of the subjects below 80% of the predicted value. Logistic regression demonstrated VC to be sufficient for optimal discrimination of asbestos-exposed subjects from a group of matched controls. No further discriminatory power was gained by additional spirometric measures, lung mechanics, blood gas analysis, or diffusing capacity. Smoking had an influence on dynamic but not on static lung volumes. In conclusion, reduced static lung volumes among smoking asbestos-exposed workers with pleural plaques should, in the absence of other lung diseases, be mainly attributed to the asbestos exposure.
Br J Ind Med 1987 Aug;44(8):550-558
Department of Pathology, University Hospital, Lund, Sweden.
Histological slides from the lungs of 89 dead asbestos cement workers have been examined with respect to ferruginous bodies and fibrosis. The results have been compared with individually matched controls with no known exposure to asbestos, and related to asbestos exposure, expressed as duration of exposure and cumulative asbestos dose, and smoking habits. The asbestos cement workers studied had been employed for on average 15 years, with a mean cumulative dose of 26 fibre-years per ml (f-y/ml). Clear dose-response relations between exposure (duration of exposure and cumulative asbestos dose) and level of ferruginous bodies were found. An association was evident already at a low cumulative dose (1-10 f-y/ml). Fibrosis was more common and more pronounced among the exposed workers than among controls. An association between ferruginous bodies and fibrosis was also found. Among the controls, but not among exposed workers, there was an association between smoking history and fibrosis.
World J Surg 1987 Aug;11(4):541-547
Anticancer Res 1987 Jul;7(4B):853-856
Department of Oncology, University Hospital, Lund, Sweden.
In 65 young women undergoing curettage for benign uterine disorders a significant relationship was found between early oral contraceptive use (starting age less than 25 years) and a high ratio of ln plasma prolactin versus ln estrogen receptor concentration of the uterine mucosae (p less than 0.047, Mann-Whitneys U-test). Year of birth, age at menarche, age at first full term pregnancy, parity, menstrual cycle phase and duration of oral contraceptive use could not explain the results. Because similar results have previously been found for breast cancer patients using plasma prolactin and breast tumour estrogen receptor concentration, the findings indicate that early oral contraceptive use permanently alters plasma prolactin levels and estrogen receptor concentration, both in benign uterine tissue and in malignant breast tumours.
Scand J Work Environ Health 1987 Jun;13(3):221-231
The sum of two exponential functions was fitted to the decay of blood lead (PbB) level after the end of lead exposure. For two subjects who had not formerly been occupationally exposed to lead but who had been exposed to a single short heavy dose, the fast compartment (probably soft tissues) had a biological half-time of 27 and 44 d, respectively. For 20 lead workers after the end of occupational exposure, the corresponding median was 29 (range 7-63) d. For 21 ex-lead workers, the median biological half-time of the slow compartment was 5.6 (range 2.3-27) years. There was significant interindividual variation in both the fast and the slow half-time. This finding probably means a considerable variation in risk at a certain exposure level. In the lead workers, the PbB fraction corresponding to the slow compartment had a median as high as 1.8 (range 0.7-2.7) mumol/l, which constituted more than half of the total PbB. This fraction was associated with exposure history, and with the lead level in the skeleton, the latter determined in vivo by an X-ray fluorescence method. The data thus indicate a rather rapid turnover of the skeletal lead pool, a phenomenon which may affect the PbB level considerably.
Lancet 1987 Mar 14;1(8533):636
Anticancer Res 1987 Mar;7(2):235-242
Flow cytometry was used for the investigation of the DNA distribution in biopsy specimens from 72 patients with squamous cell carcinoma of the uterine cervix. A prospective grading score system using tumor cell parameters and tumor host parameters was also applied. 50% of the tumors were aneuploid with up to 4 different tumor populations. The definition of DI +/- 8% was applied. The median age of the patients was 61 years with FIGO median value of 2B. Significant correlations were observed between ploidy and MGS-scores and stage stadium according to FIGO. Increasing MGS score was noted with increasingly distorted ploidy. No significant difference was found between DI below and above 1.5 for MGS, FIGO stage stadium, histology according to Ackerman, tumor parameters and tumor host parameters for the total material. However, for aneuploid tumors MGS and tumor cell parameters were related with DI below and above 1.5 (P = 0.05 and P = 0.02, respectively). No correlation between clinical stage according to FIGO and S-phase % was noted. It remains to be settled to what extent DNA flow cytometry and MGS-scoring in our ongoing prospective series of invasive squamous cell carcinoma of the uterine cervix can take their place in the multifactorial prognostic index suggested by Jacobsen et al (Am. J. Clin. Oncol. 8: 39, 1985).
Cancer Genet Cytogenet 1987 Mar;25(1):55-64
The cytogenetic findings in samples from 106 patients with non-Hodgkin lymphomas (NHL), histopathologically classified according to the Kiel classification, have been correlated with survival time. Clonal chromosomal abnormalities were found in 60 patients, and only normal karyotypes in ten. The chromosome analysis of the remaining samples failed. The failures did not differ in survival compared with the cytogenetically successful cases, indicating that this group is not a prognostic entity within NHL. The cytogenetic findings were classified in six ways in order to evaluate the prognostic value of the cytogenetic pattern. Multivariate analysis demonstrated that presence of clonal chromosome abnormalities and the number of aberrations both were important prognostic factors independent of histopathology, whereas, the modal chromosome number, presence of translocations, or unidentified marker chromosomes were not. Some characteristic chromosome abnormalities were correlated with survival time: Patients with a 1p+ marker or +7 had a significantly shorter survival time than patients with normal karyotypes only (NN). Patients with +3, +12, 6q-, i(17q), and t(14;18)(q32;q21) did not differ significantly from the NN group.
Acta Oncol 1987 Jan;26(1):27-32
Measurements were performed at 37 degrees C on 49 fresh samples excised from cancerous (n = 16) or non-malignant (n = 33) thyroid tissues of 23 patients. They were carried out for protons at a frequency of 10.7 MHz with pulse sequences (90 degrees-t-90 degrees) and (90 degrees-t-180 degrees-t) for T1 and T2 respectively. The estimates were correlated to histopathology with quantitative measurements of the proportions of colloid, thyroid epithelium, fibrosis, and haemorrhage tissue. Discriminant analysis of malignant and non-malignant tissues using T1 and T2 values, was not successful. T1 and T2 values were correlated to each other. Both were correlated to the proportions of water, thyroid epithelium and haemorrhage and inversely correlated to the amount of colloid. Multiple regression analysis revealed that T2 values were more tissue-specific than T1 values. The analyses indicate possibilities to identify different thyroid tissues by magnetic resonance imaging, especially by T2 weighted MR images.
Ann Chir Gynaecol 1987;76(2):88-92
Six hundred and forty-four patients with primary malignant tumours of the female genital tract were subject to a two-stage screening program on admission, with clinical examination in all and mammography in 380. Clinical examination alone revealed 4 cancers, while supplementary mammography screening of 369 patients with normal clinical examination revealed an additional 6 tumours, of which 5 were invasive. The prevalence rate was about three times that found in two mass-screening programs in different parts of Sweden. Thus, it could be concluded that there is an increased risk for mammary carcinoma in patients with gynaecologic malignancies. It seems reasonable therefore, to recommend mammography routinely in this group of patients.
Acta Oncol 1987;26(5):387-389
Department of Oncology, University Hospital, Lund, Sweden.
Sci Total Environ 1986 Dec 31;58(3):225-229
Blood-lead levels were determined, each summer during the period 1978-1984, in children from Scania in Southern Sweden. A total of 1395 determinations were made. The average blood-lead concentration was 55 (range 14-250) micrograms 1(-1). There was a statistically significant decrease over time, both in rural and urban areas, averaging about 4 micrograms 1(-1) per year. Lead exposure has thus decreased remarkably. One possible explanation is the contemporary, considerable reduction of the alkyl lead content of petrol.
Scand J Work Environ Health 1986 Dec;12(6):545-551
A retrospective cohort study was performed on a group of 664 male workers employed for at least one month during the period 1942-1979 in a chemical factory. Both established and suspected carcinogens had been handled in the plant, primarily piperazine, but also urethane, ethylene oxide, formaldehyde, and organic solvents. A significantly increased mortality, compared with the regional death rate, was observed in the cohort. The increase was mainly due to violent deaths and cardiovascular diseases. No rise in death rates was observed for asthma, bronchitis or emphysema, in spite of other evidence of a high risk of occupational asthma, due to exposure to piperazine. A statistically significant increase in cancer morbidity was observed for malignant lymphoma/myelomatosis when an induction latency time of at least 10 years was used. Furthermore, an increase in bronchial cancer was noted, but it was statistically significant only when an induction-latency time of at least 15 years was used. A case-referent study within the cohort did not reveal any significant association between any specific chemical exposure and cancer morbidity.
Controlled Clin Trials 1986 Dec;7(4):290-305
Multicenter clinical trials are often large and complex, involving many institutions and investigators. The organizational structure is of vital importance in conducting and coordinating such trials. The present article describes the organization of a multicenter trial of adjuvant therapy of breast cancer. The trial is conducted since 1978 and involves all 15 hospitals in the Southern Swedish Health Care Region. The paper also describes methods of determining patient accrual rate, compliance with entrance criteria, diagnostic procedures, treatment, and follow-up. Comparison of data obtained from a population-based regional tumor registry revealed an accrual rate of more than 80%. Compliance with entrance criteria varied between the treatment groups from 85% to 97%. No patients were lost to follow-up. Compliance with diagnostic procedures and treatment was generally good. Reporting of recurrences was in accordance with data from patients' records in 98% of patients. One hundred thirteen patients died during the first 5 years of study. Twenty-one of these deaths were not reported to the secretariat. This strongly illustrates the necessity of matching to a population register before presenting data of such trials.
Br J Surg 1986 Sep;73(9):727-731
All 72 resections for colorectal liver secondaries during the period 1971-1984 were analysed retrospectively. Liver tumours were single in 35 (49 per cent), unilateral in 55 (76 per cent) and associated with extrahepatic disease in 12 (18 per cent) patients. Operative mortality was 5.6 per cent. With respect to the disease in the liver, the presence or absence of four or more metastases was the predominant prognostic determinant with a 5 year survival rate of 20 per cent in patients with less than four liver tumours, and no 3 year survivor among patients with four or more tumours. When the number of liver tumours was less than four, the prognosis in patients with unilateral disease was not significantly better than in patients with bilateral disease (P = 0.19). No other liver disease variable seemed to play any role in the prognosis. Extrahepatic disease was associated with a poor prognosis and no 5 year survivor. The length of the tumour-free resection margin was the only treatment variable that varied with the outcome: a resection margin of less than 10 mm was followed by a poor survival. Variables that did not influence survival included uni- or bilateral disease, liver tumour volume, tumour size, type of liver resection, Dukes' classification, differentiation of the primary tumour and synchronous or metachronous disease. It is concluded that resection for liver colorectal secondaries is indicated when there are less than four liver tumours, even if bilateral, no extrahepatic disease is present, and a resection margin of at least 10 mm can be obtained. It should not be performed unless all of these requirements are met.
Diabetes Care 1986 Jul;9(4):359-364
In a prospective study, 270 women who gave birth to infants weighing greater than or equal to 4500 g (large baby, LB) underwent an oral glucose tolerance test (OGTT) within the first week of the puerperium. Of these women, 179 (66.3%) were retested 3-10 yr later, and 236 (87.4%) were also evaluated 20-27 yr later. The frequency of pathologic OGTTs increased with time, but the tests were of little prognostic significance for the individual patient. Women who had borne LBs developed non-insulin-dependent diabetes mellitus (NIDDM) six times more often than did a control group of women matched for age and parity and with the same period of follow-up. However, patients who developed NIDDM were also very obese, of high parity, and had a positive family history for diabetes mellitus in a high percentage of cases. Women with LBs as the only risk factor did not develop NIDDM in our study. We conclude that the birth of one LB is of minor, if any, importance in the subsequent development of NIDDM.
Acta Radiol Oncol 1986 Jul;25(4-6):281-284
Nicotinamide is an inhibitor of adenosine diphosphate ribosyl transferase (ADPRT) which is involved in the mechanism of DNA repair after high doses of ionizing radiation. C3H mice with transplanted mammary adenocarcinomas were treated with low doses of nicotinamide, 10 mg/kg, 5 days a week, and in combination with ionizing radiation, 30 Gy, using different drug dose schedules. Mice given nicotinamide in combination with irradiation took a longer time to reach a tumor volume of 1,000 mm3 and a higher complete response rate (i.e. defined as total disappearance of the tumor for at least 7 days) than those given radiation alone. This was true whether nicotinamide was given daily from one week before tumor transplantation until the animal was killed or from transplantation day until day of irradiation. In addition, nicotinamide given per os at a dose between the recommended maximum daily allowance for human subjects (20 mg/70 kg), and the therapeutic allowance (1 g-12 g daily) 5 days a week for 9 weeks, showed a radiosensitizing effect without any histologically detectable damage to the normal tissues of the mouse, including bone marrow, intestine and the liver.
Cancer 1986 Apr 1;57(7):1405-1414
The European Organization for Research on Treatment of Cancer (EORTC) Thyroid Cancer Cooperative Group presented a prognostic index in 1979 that included all histologic groups of thyroid carcinomas, and was based on a multivariate analysis of 507 patients with a median follow-up of 40 months. The current report not only uses a multivariate analysis to study the clinical validity and reproducibility of this index on case material consisting of 226 differentiated thyroid carcinomas with a considerably long follow-up (11 years), but also it investigates possible prognostic factors, other than those proposed by the EORTC. Three EORTC variables could be reproduced as important: age at diagnosis, locally advanced disease, and distant metastases. Of the additional histopathologic variables tested, microscopic tumor invasion beyond thyroid capsule (pT4) and marked cellular atypia (MCA) proved to be significant. When the effect of the age-correlated tumor factors pT4 and MCA of differentiated thyroid carcinomas were taken into consideration, age alone lost its prognostic importance as a guide for treatment.
J Surg Oncol 1986 Apr;31(4):246-254
A consecutive series of 73 patients treated with intraarterial infusion of 5-fluorouracil (5-FU) for liver metastases from colorectal primary was studied retrospectively using multivariate analysis in order to find determinants of survival. Nontreatment factors had a great impact on variation in survival with liver tumor volume and metastases to lymph glands in the liver hilum as major prognostic determinants. In addition, survival from onset of treatment varied with the interval between the primary operation and the diagnosis of liver metastases. Treatment with intraarterial 5-FU was more effective when administered at long-term (3 months every 6 months) than at short-term (5 days every 6 weeks). Single temporary dearterialization, used as an adjunct to infusion of 5-FU, had a negative impact on length of survival and was followed by a high frequency of complications. The occurrence of hepatic arterial thrombosis was associated with comparatively good prognosis.
Br J Cancer 1986 Apr;53(4):579
J Bone Joint Surg [Br] 1986 Mar;68(2):223-228
We report 60 synovectomies of the knee in 51 children with juvenile chronic arthritis. Synovitis had been present for an average of 5 years and the average age at operation was 13 years. Results were evaluated in terms of pain, knee movement, relapse of synovitis and radiological change during a follow-up averaging 7.5 years. The relief of pain was rewarding and there was a slight postoperative gain in range of knee movement in most cases. The older the patient at onset of disease, the greater the risk of pain during follow-up. Progressive joint destruction was more common in younger patients, those with systemic or polyarticular disease, and those with highly active disease at the time of operation. Recurrence of synovitis was more frequent in patients who had their operation in a phase of high disease activity; this occurred most often in patients with polyarticular disease.
Med Oncol Tumor Pharmacother 1986;3(2):77-81
In a population-based group of women, consecutively diagnosed, with premenopausal breast cancer there was a significant correlation between tumour size and plasma prolactin (r = 0.30; P less than 0.004). The concentration of estrogen receptor was negatively correlated to tumour size (r = 0.17; P less than 0.09). There were no substantial correlations between tumour size and progesterone receptor, plasma progesterone or estradiol. Adjustments for menstrual cycle day and age did not alter the above findings. The ratio of plasma prolactin and estrogen receptor was significantly greater (P less than 0.037) for the group of the patients that had started using oral contraceptives before the age of 20 as compared with the other patients. Consequently, the tumour size was significantly greater in the group of early users (P less than 0.003). The findings indicate that breast tumours developing in previous early users of oral contraceptives have a low estrogen receptor concentration, while these patients have higher plasma prolactin. The tumour size is greater in early users indicating a poorer prognosis than other women with breast cancer. As early use of oral contraceptives increases breast cancer risk and a high ratio of plasma prolactin and estrogen receptor concentration of the primary tumour characterize early oral contraceptive users the ratio may be a valuable marker for the breast cancer risk.
Lancet 1985 Mar 30;1(8431):748-749
Lakartidningen 1985 Mar 6;82(10):844-849
[Article in Swedish]
Br J Obstet Gynaecol 1985 Jan;92(1):19-22
A prospective longitudinal investigation of spontaneous cephalic version from breech presentation in the last trimester is reported. All pregnancies were assessed with ultrasound in the 32nd week of gestation, and were thereafter checked weekly. Of the 310 singleton breech presentations identified at 32 weeks, spontaneous cephalic version occurred in 177 (57%) while breech presentation persisted in 133 patients (43%). Of 140 patients with a breech presentation at delivery 95% were already presenting by the breech in the 32nd week. Spontaneous cephalic version was less likely in pregnancies with extended fetal legs, low birth-weight, short umbilical cord and primiparity.
Acta Radiol Oncol 1985 Jan;24(1):57-59
In thirty-one premenopausal patients with carcinoma of the breast the plasma prolactin was measured after mastectomy. A highly significant correlation between tumour size and plasma prolactin levels (p less than 0.002) was observed after adjustment for age at diagnosis and parity. At the time of the prolactin determination no clinical signs of metastatic disease were evident, suggesting that the prolactin levels were unrelated to the tumour burden.
Acta Radiol Oncol 1985 Jan;24(1):17-24
Various prognostic factors have been tested in multivariate analyses of 216 patients with papillary, follicular or medullary thyroid carcinomas without initial distant metastases. The median follow-up time was 11 years. The patient's sex was not found to be a significant predictor. Age at diagnosis seemed to be an important predictor for papillary as well as for follicular carcinomas, but when deaths in intercurrent disease were estimated, marked cellular atypia and tumour invasion beyond the thyroid capsule proved to be more important predictors. For medullary carcinomas tumour invasion beyond the thyroid capsule was the only significant predictor.
Hereditas 1984;101(2):223-226
Am J Ind Med 1984;6(5):347-357
The heterocyclic secondary amine piperazine is known to cause asthma. In a cohort of 602 workers, employed during the period 1942-1979, at a chemical industry where piperazine is handled, a study conducted by means of a mailed questionnaire showed a strong exposure-response relationship as to frequency of work-related airway symptoms indicating asthma. In the most exposed group about a third of the workers had experienced such symptoms. Age, length of employment, smoking habits, and previous work-related asthmatic symptoms, but not atopy, modified the response. Further, there was an association between piperazine exposure and chronic bronchitis. In the most exposed group every fourth subject had chronic bronchitis. The frequency was modified by smoking habits; atopy was a confounder. Although many subjects, especially high-exposed ones, left work because of airway symptoms, there was no difference in occurrence of airway symptoms between former and present employees, ie, no "healthy worker selection" ("survivor population effect").
Arch Androl 1984;12(1):113-116
One hundred-eighty-five consecutive spermiograms from men of infertile couples in 1980-1981 were compared with as many spermiograms of age-matched controls from 1960-1961. The semen parameters analyzed were: volume, sperm density, and sperm morphology. The following significant changes were noted over the time period: the mean seminal volume decreased from 3.79 ml to 3.42 ml (p less than 0.05), the mean sperm count decreased from 125.4 mill/ml to 78.0 mill/ml (p less than 0.001) and the proportion of double sperm heads increased from 0.52% to 1.51% (p less than 0.001). Further analysis showed even more pronounced changes in these parameters for men living in the urban area compared those from the surrounding rural areas.
Acta Radiol Oncol 1984;23(1):55-59
A visually increased uptake of 201Tl chloride corresponding to a 'cold' (131I or 99Tcm ) thyroid nodule is mostly seen in well-differentiated carcinomas but also often in follicular adenomas. Since a visually increased uptake of 201Tl can be due to an increased initial uptake and/or a delayed elimination, an extended dynamic investigation was performed in patients with well-differentiated carcinomas or with follicular adenomas. Data were collected in a dynamic simultaneous double isotope ( 99Tcm + 201Tl) study up to 50 min after intravenous administration. Adenomas could be significantly separated from carcinomas by the elimination (p = 0.0001), but not by the initial uptake.
Acta Radiol Oncol 1984;23(6):443-448
Eighty-six patients with invasive squamous cell carcinoma of the vulva stage I were followed for 2 to 20 years after surgical treatment varying from local excision to radical vulvectomy with inguinal lymph node dissection. The results are presented and the prognosis discussed in relation to the radicality of the surgical intervention, the degree of tumour differentiation, the morphologic properties of tumour cell population, and the tumour host relationship. The most important prognostic factor seemed to be the radicality of the surgical intervention. To reduce patient morbidity in radical surgery while still achieving a comparable survival rate an operative approach with less than radical vulvectomy, inguinal dissections or pelvic lymphadenectomy, or both, is proposed for selected patients.
Arch Androl 1983 May;10(2):127-133
The spermiograms of 63 fertile men (whose female partners were pregnant at the time of examination) were evaluated. A wide Gaussian distribution of the different semen parameters was found. Both parametric and nonparametric statistical tests were applied and gave almost identical results. In a subgroup of 34 men, a second semen sample was analysed, but a significant difference (p less than or equal to 0.05) between the two samples was found only regarding the proportion of abnormal forms. Between various semen parameters significant correlations were found. There was no association between follicle stimulating hormone (FSH) and sperm density with sperm counts greater than 20 mill/ml.