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To investigate the association between human herpesviruses and multiple sclerosis (MS), as well as between measles virus and MS.

Process retrofit (PR) is becoming a key issue for many existing industrial chemical processes due to the changing prices and market conditions, the emerging new design methodologies, as well as to environmental regulations. PR is sometimes far more complicated than process grassroots design, and it is usually team‐based work in which many departments and disciplines are concerned. Thus, it is very important to rationally organize the work and cooperation of the team members involved in the PR project. In this paper, we present some insights on the significance of PR, the methods for identifying the bottlenecks, as well as the principles and strategies of completing a retrofit project. A systematic procedure for process retrofits is developed based on the experience of several industrial retrofit projects.

Case-based reasoning (CBR) is an approach based on the reuse of the past experiences in finding the solutions to the new, similar problems. Adaptation is the most difficult and the most important step in the succesful use of CBR system, especially if in the certain applications e.g. equipment design the non-numerical parameters have to be adapted. The objective of the paper is a presentation of the adaptation method of CBR that is based on rough sets. Two examples are given to illustrate the applicability of the different adaptation methods

In the rural province Masvingo in Zimbabwe, 25% of maternal deaths were caused by obstetric haemorrhage, which had a cause specific maternal mortality rate (MMR) of 40 per 100 000 live births. Forty per cent of cases were due to a ruptured uterus, and 30% to an atonic uterus. Forty-two per cent were more than 35 years old and 44% para 5 or more. In spite of antenatal coverage for 85% of the women, 42% died outside any health facility. Fifty per cent of the women had had no intervention whatsoever before death from haemorrhage. The most important factor for prevention at community level is provision of emergency transport, which would have saved 50% of the women. Other non-health service factors contributing to the adverse outcome were found in actions of the patient herself or a traditional birth attendant. In the health services avoidable factors were identified in 58% of women. More effective antenatal attention to high risk factors, especially high age and parity, appropriate use of maternity waiting shelters, action programmes for management and haemorrhage at all levels, basic resources for resuscitation, improved surgical skills with supervision and available transport for referrals are all necessary parts of a programme to prevent maternal deaths from obstetric haemorrhage.

Objective:To elucidate whether microbial infections are involved in the etiology of intrauterine death. Methods:One hundred four cases of stillbirth of unknown etiology and 96 age- and parity-matched referents with live births were analyzed with respect to microbial infection by cultures from the placenta, endocervix and internal organs of the fetuses, exteral sites of the babies and fetuses, and by serology for bacteria, viruses and Toxoplasma gondii. Results:In 17 cases in whom no other infectious agent was diagnosed, Escherichia coliwas isolated from the placenta and one or more internal fetal organs. Tests for Treponema pallidumand Toxoplasma gondiiwere more frequently positive in cases than in referents (O.R. 8.3 and 3.9, respectively). There was no increased risk for intrauterine death in women with human immunodeficiency virus, cytomegalovirus, herpes simplex virus or rubella virus. Conlusions:Our findings indicate that infections remain an important case of intrauterine death in Zimbabwe.

The use of case-based reasoning in the mixing equipment selection is promising. Its main advantage is use of high quality, verified knowledge and easiness of updating. The main functions of the system are a systematic documentation of the cases and an accumulation of experience.

Glutathione transferases from rat kidney cytosol were purified about 40-fold by chromatography on S-hexylglutathione linked to epoxy-activated Sepharose 6B. Further purification by fast protein liquid chromatography with chromatofocusing in the pH interval 10.6-7.6 resolved five major peaks of activity with 1-chloro-2,4-dinitrobenzene as the second substrate. Four of the peaks were identified with rat liver transferases 1-1, 1-2, 2-2 and 4-4 respectively. The criteria used for identification included physical properties, reactions with specific antibodies, substrate specificities and sensitivities to several inhibitors. The fourth major peak is a ‘new’ form of transferase, which has not been found in rat liver. This isoenzyme, glutathione transferase 7-7, has a lower apparent subunit Mr than any of the transferases isolated from rat liver cytosol, and does not react with antibodies raised against the liver enzymes. Glutathione transferases 3-3 and 3-4, which are abundant in liver, were only present in very small amounts. In a separate chromatofocusing separation in a lower pH interval, an additional peak was eluted at pH 6.3. This isoenzyme is characterized by its high activity with ethacrynic acid.

A questionnaire of respiratory symptoms and diseases completed by 6610 adults in 3 age cohorts (35–36 y; 50–51 y and 65–66 y) in northern Sweden was followed-up by interview and lung function testing of 1243 subjects with asthmatic or bronchitic symptoms and 263 subjects assessed from the postal questionnaire as being healthy. We report the results of this follow-up study.

All incident cases of diabetes mellitus in the age group 15 to 34 years have been prospectively registered in Sweden since January 1983. To analyse the utilization of outpatient services 8 years after disease onset, we selected the cases registered in 1983 and two controls per case from the general population, matched by age, gender, and county of residence. In 1991, retrospective data about utilization patterns during a 3‐month period were collected via a mailed questionnaire, returned by 317 (72 %) patients with diabetes and 586 (68 %) controls. Seventy‐four percent of the cases and 19 % of the controls reported at least one visit to a hospital outpatient clinic, including accident and emergency departments. The odds ratio for one visit was 14 (95 % CI 9.6–20), for two visits 11 (95 % CI 7.0–18), and for three or more visits 8.9 (95 % CI 5.6–14). Even when specialized diabetes clinics were excluded from the analysis, the cases had higher odds for visits to internal medicine clinics, to ophthalmology clinics, and to gynaecology clinics, but not for visits to surgical clinics or to accident and emergency departments. Of non‐hospital outpatient services, only visits to nurse practitioners were reported by a higher percentage of diabetic responders. Twenty‐seven percent of patients with diabetes, as compared to 9 % of the controls, had visited both hospital and non‐hospital outpatient offices. Females were overrepresented among diabetic high‐consumers. The results indicate that most young to middle‐aged Swedish persons with diabetes are monitored at hospital outpatient offices, but considerable overlap exists between hospital and non‐hospital outpatient services. Further research is needed into the determinants of utilization patterns in diabetes, such as gender.

The association between standardized cancer mortality rate ratios from 1969-1978 and dietary practices was examined in an ecologic study of the 24 counties of Sweden by means of several independent data sources. The study supports the hypothesis that a high intake of cereal fiber protects against colorectal cancer (r = -0.75 for males and r = -0.67 for females). This study found no association between fat intake and colorectal cancer. However, a negative correlation between milk consumption and this type of cancer was found. A suggested hypothesis is that calcium protects against colorectal cancer, since milk is the major source for calcium intake in Sweden. This could indicate that, for societies with a high fat intake, preventive measures which increase the intake of fiber and milk or calcium might have a greater impact on mortality from cancer of the colon and rectum than would a moderate decrease in the intake of fat. There are no indications in this study that fat intake promotes breast cancer.

Identification of the main operational factors in cases of maternal death within and outside the health care system is necessary for safe motherhood programmes. In this study, a follow-up was done of all 117 cases of maternal deaths in Ilala district, Dar es Salaam, 1991-1993, at all levels of care. In all, 79% received some medical care whereas 11% arrived too late for treatment. For each case the major operational factors and all health care interventions were defined through interviews with family members and health care staff and from hospital records, and the avoidability of each case was determined. In the health institutions where the women had consulted, the available resources were assessed. It was found that in most cases the husband (29%) or the mother (31%) of the woman decided on her care in cases of complications, and together with the lack of transport, this often caused delay at home. Also, delay in transfer from the district hospital was common. Cases of abortion complications were often not managed on time because of the delay in reporting to hospital or misleading information. Suboptimal care was identified in 77% of the cases reaching health care. Inadequate treatment was identified by the district health staff in 61% and by the referral centres in 12% of their cases. Wrong decision at the district level and lack of equipment at the referral centre were the main reasons for inadequate care. It is concluded that although community education on danger signs in pregnancy and labour is important, provision of the core resources and supplies for emergency obstetric interventions, as well as clear protocols for management and referral, are absolutely necessary for improvement of maternal survival.

Most studies evaluating immune markers for prediction of Type 1 (insulin-dependent) diabetes mellitus have focused on first degree relatives, although only 10 % of newly-diagnosed patients have an affected first degree relative. The Swedish Childhood Diabetes Register identifies 99 % of all diabetic children at diagnosis. In this population-based study, islet cell antibodies and insulin autoantibodies in 0–14-year-old Swedish consecutively-diagnosed patients and control subjects were analysed to define their sensitivity and specificity. Over 16 months (1986–1987), 515 Swedish children developed diabetes. Plasma samples were obtained from 494 (96 %) patients, and 420 matched control children. Among patients, the frequency of islet cell antibodies was 84 % (415 of 494), insulin autoantibodies 43 % (145 of 334); 40 % (135 of 334) were positive for both and 88 % (294 of 334) were positive for one or both. Among control children, 3 % (14 of 420) had islet cell antibodies, 1 % (4 of 390) insulin autoantibodies, and 4 % (16 of 390) had either autoantibody marker. The predictive value of finding a patient with the disease was only 7% since 4 % of the control children were antibody-positive and the cumulative incidence rate up to 15 years of age is 0.38 %. None of the autoantibody-positive (n= 21) or negative control children developed diabetes during 3 to 5 years of follow-up. Longitudinal investigations of islet cell or insulin-autoantibody-positive healthy children are necessary to accurately determine the conversion rate from marker positivity to disease onset.

The incidence of diabetes mellitus in Sweden in the 15–34 year age group was prospectively studied on a nationwide basis, beginning 1 January 1983. A total of 1,214 male and 720 female cases of newly-diagnosed (excluding gestational) diabetes were reported over a 5-year period. This corresponds to an incidence of 20.5 per 100,000/year in male subjects and 12.7 per 100,000/year in female subjects. Most cases were classified as Type 1 (insulin-dependent) diabetes, with an incidence of 15.9 in males and 8.6 in females. The incidence of Type 1 diabetes decreased gradually with age, while the incidence of Type 2 (non-insulin-dependent) diabetes increased. A male predominance was found in all age groups, with a male-to-female ratio of 1.8∶1 for Type 1 diabetes and 1.3∶1 for Type 2 diabetes. Maximum blood glucose concentration at diagnosis was significantly higher in males than in females in both Type 1 and Type 2 diabetic subjects. In contrast, the percent desirable weight was significantly higher in females, both in Type 1 and Type 2 diabetic subjects. The difference in diabetes incidence therefore cannot be attributed to any methodological error. The present finding of a marked male predominance after puberty in Type 1 diabetes in an ethnically quite homogeneous population supports the hypothesis that environmental risk factors and life-style are important for the development of the disease.

In a nationwide incident case referent study we have evaluated vaccinations, early and recent infections and the use of medicines as possible risk determinants for Type 1 (insulin-dependent) diabetes mellitus in childhood. A total of 339 recently onset diabetic and 528 referent children, age 0–14 years, were included. Information about infections was collected from a mailed questionnaire and about vaccinations from childhood health care centres and schools. When vaccinations were considered as possible risk factors for diabetes, a significant decrease in relative risk estimated as odds ratio (OR) was noted for measles vaccination (OR=0.69; 95% confidence limits 0.48–0.98). For vaccination against tuberculosis, smallpox, tetanus, whooping cough, rubella and mumps no significant effect on OR for diabetes was found. The odds ratios for Type 1 diabetes for children exposed to 0, 1–2 or over 2 infections during the last year before diagnosis of diabetes revealed a linear increase (OR = 1.0,1.96 and 2.55 for 0, 1–2 and over 2 infections, respectively). The trend was still significant when standardized for possible confounders such as age and sex of the children, maternal age and education and intake of antibiotics and analgetics. In conclusion, a protective effect of measles vaccination for Type 1 diabetes in childhood is indicated as well as a possible causal relationship between the onset of the disease and the total load of recent infections.

Using the Swedish childhood diabetes register, a nationwide, case-referent study was performed from September 1, 1985 to August 31, 1986. Based on the information from a mailed questionnaire sent to all incident diabetic children and for each diabetic child — two referent children matched according to age, sex, and county, we have analysed perinatal events and aspects of the social environment as possible risk factors for Type 1 (insulin-dependent) diabetes in childhood. A significantly larger proportion of the mothers of the diabetic children were older than 40 years compared to those of the referent children (33% and 24%, p=0.01 respectively). A smaller percentage of mothers of the diabetic children had a high educational level compared to mothers of referent children (10% and 15%, p=0.03 respectively) and 39% of the fathers of the diabetic children were manual workers compared to 31% of the fathers of referent children (p=0.03). Perinatal events did not differ between diabetic and referent children. In children 0–6 years, the duration of breast-feeding was significantly shorter in diabetic children than among referent children (median duration for diabetic children 5 months compared to 6 months for referent children p=0.03). When considering the presence of Type 1 diabetes among relatives, maternal age over 40 years, low educational level of the mother, and the father being a manual worker as risk factors, the presence of 1 to 4 of any of these risk factors increased the relative risk for Type 1 diabetes cumulatively from 1.2–7.5. In conclusion, breast-feeding habits and probably other factors dependent on maternal age and the social status of the family may further increase the risk for Type 1 diabetes in genetically susceptible individuals.

From July 1, 1977 to July 1, 1986, 3,503 incident cases of Type 1 (insulin-dependent) diabetes mellitus were registered in the Swedish childhood diabetes study. Using data from this register and from a case-referent study, including all incident Type 1 diabetic children in Sweden during one year and, for each patient, two referent children matched according to age, sex and county, we have studied the associations between Type 1 diabetes and familial Type 1 and Type 2 (non-insulin-dependent) diabetes, thyroid, adrenal, allergic, rheumatic, heart and bowel disease. The mean annual incidence per 100,000 during the nine year period was 25.1 for boys and 23.5 for girls. In 8.5% of the patients, one parent had Type 1 diabetes, 73% of whom were fathers. Fifty-six of the patients (1.7%) had a parent with Type 2 diabetes. The prevalence of parental Type 1 diabetes tended to be higher in patients with younger age at onset; whereas, the opposite was found for patients with parental Type 2 diabetes. In the case-referent study, the age-adjusted odds ratio for Type 1 diabetes when a first and/or second degree relative had Type 1 diabetes was 5.5 (95% confidence limits 4.0–7.7), and in accordance with the findings of the case register, the odds ratio tended to be highest in patients with the youngest age at onset. Season at onset of the patients was not associated with parental Type 1 diabetes. The odds ratio for Type 1 diabetes was significantly increased 3.3 (95% confidence limits: 2.3–4.6) when Type 2 diabetes was reported in relatives (three generations). Odds ratios were also significantly increased (p(0.05) when thyroid or rheumatic diseases were reported among relatives. It is concluded that although the majority of incident Type 1 diabetic children lack family history, parental Type 1 diabetes may influence the age at onset of the disease but has no effect on sex distribution of these children. An increased risk for Type 1 diabetes in children is also indicated when Type 2 diabetes, (non-insulin-treated) thyroid or rheumatic disease is reported in relatives.

This study analyses data from two nationwide prospective diabetes registries now covering about 3400 cases from 19 million person-years of follow-up in the age group 0-34 years. The risk of developing insulin-dependent diabetes mellitus (IDDM) per 100000 individuals before 15 years was 386 (95% confidence intervals (Cl) : 362–410) for boys and 391 (95% Cl: 367–415) for girls and by 35 years 701 (95% Cl: 671–731) for men and 562(95% Cl: 534–690) for women. The incidence rate showed a maximum for both boys and girls in early puberty. After pubertal years a sharp increase in the male to female incidence ratio of IDDM was notable. At 10–14 years it was 0.94, at 15–19 years 1.59 and at 20–24 years 2.08. A Cox regression model was used to analyse the effects on age at onset of sex, population density and climatological factors as measured by north-south area of residence and season at onset. The effect of sex was confirmed (P<0.001). A significant effect (P = 0.004) of season was shown when the four seasons were classified according to a four stage scale related to mean temperature. When dividing Sweden into 11 regions according to north-south gradient (Latitude 55�, 56�, 57�, …, 65�) a significant effect (P = 0.038) was also found. However, no effects of population density or living near the coast versus in the interior were found. It is concluded that a large proportion of the young are at risk of developng this chronic disease. In addition to genetic influences the time of disease onset seems to be related to puberty, gender, and climatological and other environmental factors as indicated by a pattern of geographical and seasonal variation.

Nystr�m L (Department of Epidemiology and Health Care Research, University of Umeā Umeā Sweden), Dahlquist G, Rewers M and Wall S. The Swedish childhood diabetes study. An analysis of the temporal variation in diabetes incidence 1978–1987. International Journal of Epidemiology 1990; 19: 141–146 The Swedish Childhood Diabetes Register combines continuous prospective reporting on incident cases and regular retrospective review of hospital records in all paediatric departments in the country and has, from 1978 to 1987, compiled 3838 cases. A validity test using an independent source has revealed a degree of ascertainment of 100%. When fitting a linear regression model to the natural logarithm of the yearly incidence rates, a significant increase over time was found for girls and for both sexes combined. To analyse the time trend with respect to age, sex, calendar year and birth cohort and their interactions, Poisson regression modelling was used. There was a significant age effect and between age and sex. When these age and sex effects were taken into account a significant increase over time was found. Calendar period had a significant effect when adjusted for cohort effects whereas cohort did not add significantly to the explanation of the variance. There was no significant interaction between sex and calendar period indicating similar time variations for both sexes. The temporal variability was also apparently similar among different age groups. The observed increase of childhood insulin-dependent diabetes mellitus (IDDM) affecting both sexes and all age groups, strongly supports the importance of environmental factors in the aetiology of IDDM.