Comparison between the proteins of human brain myelin in subacute sclerosing panencephalitis, Amyotrophic lateral sclerosis and malignant diseases

The proteins of human brain myelin were analysed by means of horizontal polyacrylamide gel electrophoresis in 2 cases of subacute sclerosing panencephalitis (SSPE), in 2 cases of amyotrophic lateral sclerosis (ALS) and in a number of middleaged and elderly individuals without neurological disease. The brain samples were taken at autopsy.The adult-type protein pattern was well preserved at least until 78 years of age. The encephalitogenic basic protein was decreased in both cases of SSPE. The lighter proteolipid protein was markedly increased in 1 SSPE case. These two protein bands were normal in ALS. Instead, one protein with a heavy molecular weight, always present in normal myelin, was absent from both ALS specimens. Another protein, never previously seen, was present among the heavy molecular weight proteins. The encephalitogen was markedly reduced in 3 non-neurological patients all of whom were found to have malignant disease.It is concluded that these findings suggest some heterogeneity of the demyelinating process in various cases of SSPE. They may also indicate age-dependent differences in attempts to restore the structural proteins of myelin. The changes observed in ALS confirm the different nature of the pathogenesis of that disease, as compared to the so-called primary demyelinating conditions. Cancer may lead to a decrease in the amount of the encephalitogen in CNS myelin.     

FURTHER STUDIES ON THE EPIDEMIOLOGY OF MULTIPLE SCLEROSIS IN FINLAND

The places of birth of 1,000 Finnish patients with multiple sclerosis (MS) were located according to the population statistics of 1930. The highest frequency of the disease was found in a small district, Jalasjärvi, composed of 6 rural communes in the western high-risk area of the country. One animal disease, nutritional muscular dystrophy of the cattle (NMD), appeared to be very common in the same western area and, in 1970, its highest frequency was also found in the Jalasjärvi district. Some western accumulation was found in the cases of two viruses of cereals, European wheat striate mosaie virus (EWSMV) and oat sterile dwarf virus (OSDV), but both of them were rare in the southwestern part of Finland where the prevalence of MS was high.     

Concurrent radiotherapy and weekly paclitaxel for locally advanced or recurrent squamous cell carcinoma of the uterine cervix. A pilot study with intensification of dose

OBJECTIVE: This study included patients with inoperable primary or recurrent cervical cancer whose treatment plan called for exclusive radiotherapy. The endopoints of the study were to confirm the feasibility of concurrent radiotherapy and paclitaxel in relation to potential acute toxicity and to evaluate if an increase of complete local control might be obtained with the association of paclitaxel to radiotherapy as a radiosensitizer. METHODS: Twenty patients (13 new cases, stage IIB-III, and 7 with pelvic recurrences) were enrolled and, with exclusion of one recurrence, 19 were evaluable for acute toxicity and response. In new cases, radiotherapy was conventionally administered: 50.4 Gy/28 fractions by external beam (whole pelvis) followed by intracavitary cesium or reduced transcutaneous field. In recurrences, radiotherapy was performed with external beam only through individualized fields. Paclitaxel was administered weekly at the dose of 40 mg/m2 or 60 mg/m2 during the entire course of external radiotherapy. RESULTS: Complete regression (CR) as defined by clinical and imaging examinations was achieved in eight of the 13 new cases (62%) and in four of the six recurrences (66%), for a total complete response rate equal to 63%. Five patients (3 treated with 40 mg/m2 and 2 with 60 mg/m2) experienced grade 3 small bowel toxicity, one patient treated with 40 mg/m2 grade 3 bladder toxicity and one patient treated with 60 mg/m2 had grade 4 mucositis. Out of 12 CR patients at the end of treatment, ten maintain complete local remission for a median follow-up of 47 months but two have developed distant metastases. CONCLUSION: The results confirm that this approach is feasible and suggest the use of paclitaxel as radiosensitizer in locally advanced cervical cancer.     

Risk factors for poor renal prognosis in children with hemolytic uremic syndrome

Many factors have been proposed as predictors of poor renal prognosis in children with hemolytic uremic syndrome (HUS), but their role is still controversial. Our aim was to detect the most reliable early predictors of poor renal prognosis to promptly identify children at major risk of bad outcome who could eventually benefit from early specific treatments, such as plasmapheresis. Prognostic factors identifiable at onset of HUS were evaluated by survival analysis and a proportional hazard model. These included age at onset, prodromal diarrhea (D), leukocyte count, central nervous system (CNS) involvement, and evidence of Shiga toxin-producing Escherichia coli (STEC) infection. Three hundred and eighty-seven HUS cases were reported; 276 were investigated for STEC infection and 189 (68%) proved positive. Age at onset, leukocyte count, and CNS involvement were not associated with the time to recovery. Absence of prodromal D and lack of evidence of STEC infection were independently associated with a poor renal prognosis; only 34% of patients D^–STEC^– recovered normal renal function compared with 65%–76% of D⁺STEC⁺, D⁺STEC^– and D^–STEC⁺ patients. In conclusion, absence of both D and evidence of STEC infection are needed to identify patients with HUS and worst prognosis, while D^– but STEC⁺ patients have a significantly better prognosis.     

Meal modulation of circulating interleukin 18 and adiponectin concentrations in healthy subjects and in patients with type 2 diabetes mellitus

BACKGROUND: A single high-fat meal induces endothelial activation, which is associated with increased serum concentrations of inflammatory cytokines. OBJECTIVE: We compared the effect of 3 different meals on circulating concentrations of interleukin 8 (IL-8), interleukin 18 (IL-18), and adiponectin in healthy subjects and in patients with type 2 diabetes mellitus. DESIGN: Thirty patients with newly diagnosed type 2 diabetes and 30 matched, nondiabetic subjects received the following 3 isoenergetic (780 kcal) meals separated by 1-wk intervals: a high-fat meal; a high-carbohydrate, low-fiber (4.5 g) meal; and a high-carbohydrate, high-fiber meal in which refined-wheat flour was replaced with whole-wheat flour (16.8 g). We analyzed serum glucose and lipid variables and serum IL-8, IL-18, and adiponectin concentrations at baseline and at 2 and 4 h after ingestion of the meals. RESULTS: Compared with nondiabetic subjects, diabetic patients had higher fasting IL-8 (P < 0.05) and IL-18 (P < 0.01) concentrations and lower adiponectin concentrations (P < 0.01) at baseline. In both nondiabetic and diabetic subjects, IL-18 concentrations increased and adiponectin concentrations decreased (P < 0.05) from baseline concentrations after consumption of the high-fat meal. After consumption of the high-carbohydrate, high-fiber meal, serum IL-18 concentrations decreased from baseline concentrations (P < 0.05) in both nondiabetic and diabetic subjects; adiponectin concentrations decreased after the high-carbohydrate, low-fiber meal in diabetic patients. IL-8 concentrations did not change significantly after consumption of any of the 3 meals. CONCLUSIONS: This study provides evidence that circulating IL-18 and adiponectin concentrations are modulated by familiar foodstuffs in humans. Meal modulation of cytokines involved in atherogenesis may represent a safe strategy for ameliorating atherogenetic inflammatory activity in diabetic patients.     

Potential transmission of the cytogenetic toxic effects of methotrexate in the male germline cells of Swiss mice

On testing the cytogenetic toxic effects of methotrexate, a widely prescribed antineoplastic drug, in the male germline cells of Swiss mice, it was found highly clastogenic to the spermatogonial cells at 24-h post-treatment after a single intraperitoneal exposure. The occurrence of significant percentages of aberrant primary spermatocytes with atypical bivalents at week 4 post-treatment and a little higher percentages of sperm with abnormal morphology at week 8 post-treatment indicated the potential transmission of the induced cytogenetic toxic effects of methotrexate from spermatogonia to sperm in the male germline cells of Swiss mice.     

Accrual issues for chemoprevention trials: the example of the 4-HPR study for the prevention of contralateral breast cancer

This paper describes the accrual of the controlled clinical trial with fenretinide for the prevention of contralateral breast cancer. Accrual screened 4,030 potentially eligible patients of whom 1,815 were randomized. Two strategies of recruitment were used, i.e. retrospective and prospective. In the retrospective accrual, the medical staff reviewed the records of breast cancer patients who had received curative surgery to select those who fulfilled the eligibility criteria of the study. For the prospective recruitment operated, patients were contacted after the beginning of the trial. The study started in March 1987 and accrual closed on July 31, 1993. The planned accrual period was extended by 19 months. The yearly accrual tended to decrease with time. This was mainly due to the end of the retrospective recruitment and to the introduction of adjuvant chemotherapy, a reason for exclusion from the trial, also for patients with negative axillary nodes. The known accrual difficulties of chemoprevention studies proved also to be true for the high-risk population of this trial.     

Hyperexcretion of free N-acetylneuraminic acid--a novel type of sialuria

A 26-yr-old female with increased urinary excretion of free N-acetylneuraminic acid is described. Her early history was normal but she had difficulties at school and developed epilepsy at 14. She is mildly retarded, has slight changes in the spine, but no hepato- or splenomegaly. Cerebrospinal fluid leucocytes and IgG are elevated. Liver and skin biopsies disclosed no morphological abnormality. The daily excretion of free N-acetylneuraminic acid is ca. 0.5 g, intermediate to that found in other known types of sialuria. The clinical and morphological findings are also different suggesting a novel type of sialuria.     

Registration of external causes of death in the Baltic States 1970-1997

BACKGROUND: Trends in external causes of deaths in the Baltic States--Estonia, Latvia and Lithuania--were analysed against the background of turbulent political, social and economic changes. The reliability of mortality statistics concerning external causes of death in these countries is considered to be good. METHOD: This study is based on data published by the statistical offices of the three Baltic States and on data obtained through interviews with personnel employed at the national statistical offices. The study period was divided, by socio-political and economic factors, into a period of stagnation (1970-1984) and a period of reforms (1985-1997). RESULTS: During 1970-1984 a stable slightly upward trend of external causes of death rates was observed. The curve became S-shaped in the reform period: between 1984 and 1988 a marked decrease occurred followed by a rapid increase of rates until 1994, and then by 1997 a fall to the approximate level of 1984. The male to female ratio of external causes of death was between 3.4:1 and 4.2:1. External deaths accounted for 10% to 14% of all deaths before 1984. During the period 1984-1988 the proportion of external deaths was under 10% and peaked in 1994 at 16%. Fluctuations in the trends of external death were more pronounced among males than females in all Baltic countries. CONCLUSION: Trends in external causes of death were similar in Baltic States. High proportions of violent death decreased life-expectancy for both sexes, but markedly for males. Social stresses and alcohol consumption could be considered as factors influencing the mortality rates and specific fluctuations in trends of external death, especially among males.