Stability and change in structural social relations as predictor of mortality among elderly women and men

In a follow-up study of 70–95years old women and men (n = 911) we studied the association between change and stability in three structural aspects of social relations (contact frequency, contact diversity, cohabitation status) from 1986–1990 and mortality after the next four years in 1994. Women aged 70–74years who developed low contact frequency or developed small contact diversity showed significantly higher mortality, adjusted OR_freq: 3.78 (1.08–13.20), adjusted OR_div: 3.79 (1.24–11.58). Women aged 70–74years with continuously low contact frequency showed an increased mortality compared to women constantly experiencing high contact frequency, adjusted OR: 2.75 (1.04–7.26). A tendency in the same direction for sustained small contact diversity was found, adjusted OR: 1.98 (0.70–5.61). Among women aged 75+ years no impact of frequency and diversity was demonstrated, whereas continuously living alone was a significant predictor of mortality, when compared to women continuously living with somebody, adjusted OR: 2.57 (1.29–5.09). In men, we found a significantly increased mortality among those who developed high contact frequency and developed large contact diversity OR_freq: 3.91 (1.02–14.94) and OR_div: 6.04 (1.30–28.03). In summary, we found rather larger age differences in the strength of the association between change in structural social relations and mortality. Furthermore, the associations seemed stronger among women than men, which may however mainly be explained by the small number of men in our cohort.     

The effects of chlorpromazine on the outer cell wall of Salmonella typhimurium in ensuring resistance to the drug

Chlorpromazine (CPZ), a compound employed for the management of psychosis, has a wide ranging antibacterial activity. The growth of Salmonella typhimurium100 mg/l), was initially inhibited during the first 8-16 h of exposure to concentrations of CPZ below the MIC. During this period of transient susceptibility, the distribution of ribosomes was markedly altered in a concentration dependent manner; the rough cell wall was transformed into a smooth form. The protein composition of the outer cell wall of 55 kDa was markedly decreased, whilst there was an increased number of high molecular weight proteins. After 16 h of exposure to sub-MIC levels of CPZ, the inhibitory effect of the drug was no longer apparent whereas the effects noted on the cell wall were retained. These Salmonella were, as the control, agglutinated by O antigen specific antibody. Whereas agglutination of the control Salmonella was blocked by the presence of CPZ at concentrations that induced the cell-wall effects, agglutination of CPZ exposed-Salmonella for periods in excess of 16 h was not blocked by any concentration of CPZ. These results suggested that eventual resistance to CPZ was dependent upon changes induced by CPZ at the cell wall level. The results also suggested that the CPZ binds to the 55 kDa protein and that such binding interfered with the recognition of the O antigen by antibody.     

Maximum tolerated doses of methotrexate and 7-hydroxy-methotrexate in a model of acute toxicity in rats

Purpose: After more than 50 years of methotrexate (MTX) treatment of acute lymphoblastic leukaemia (ALL), it is currently believed that as long as dose escalations are followed by adequate leucovorin rescue guided by monitoring MTX serum concentrations, hydration and urinary alkalinization, high-dose MTX (HD-MTX) can be tolerated without life-threatening toxicity. However, our recent experimental animal studies of the major metabolite of MTX, 7-OH-MTX, indicate that this concept may have some limitations. Animals with levels of 7-OH-MTX of 1 mM, which is below the levels routinely found in patients on HD-MTX, demonstrate intolerable toxicity and some animals die within 8 h. Electron microscopy indicates that endothelial cell and platelet functions are perturbed. Since animal data are lacking, and interspecies differences not known, we wanted to investigate the maximum tolerated doses of MTX and 7-OH-MTX in a rat model of short-term effects. The maximum tolerated dose was chosen instead of LD₅₀ for reasons of animal welfare. Methods: We infused MTX and 7-OH-MTX into anaesthetized male Wistar rats and monitored the animals for 8 h. The drugs were given as a bolus plus continuous infusion. The dose-finding ranges were 1.8–11.3 g/kg MTX and 0.1–1.2 g/kg 7-OH-MTX. Results: The maximum tolerated dose was between 3 and 5 g/kg for MTX and lower than 0.1 g/kg for 7-OH-MTX. The mean serum concentrations of MTX and 7-OH-MTX in animals that did not survive the 8-h period were 21.9 and 1.6 mM, respectively. The animals that received the highest MTX or 7-OH-MTX doses and concentrations died after sudden reductions in heart rate and blood pressure. Conclusions: We demonstrated a lower maximum tolerated dose of 7-OH-MTX than of MTX in rats after 8 h. The 7-OH-MTX concentrations were in the therapeutic range after HD-MTX. If the rat/human interspecies differences are not large, our data may indicate that HD-MTX regimens should not be further dose intensified, due not so much to the effects of MTX as to those of 7-OH-MTX. Received: 28 July 1999 / Accepted: 25 January 2000     

Medium Conditioned for 24 Hours by Mononuclear Human Blood Cells Contains an Inducer of Granulopoiesis Lacking Colony Stimulating Activity

Regulation of granulocyte and macrophage formation was studied by a modified CFU-C assay. Mouse bone marrow cells were cultured in methylcellulose in vitro. After colony counting on d 7, the cells were washed out to determine the total cell number per plate, and the distribution of granulocytes and macrophages in smears. By this procedure it was possible to study pathway-specific regulators. The colony stimulating factor in medium conditioned by mouse L-cells appeared specific for the macrophage cell line; 99% of the colony cells were macrophages. Medium conditioned for 24 h by mononuclear cells from human blood, had no colony forming capacity, but increased colony size and generated significant granulocyte production when combined with L-CSF. This granulopoiesis inducing factor was thermo-labile, and was mostly retained by an Amicon filter separating molecules at 100000 daltons.     

Clinical evaluation of a novel ultrasound-based bladder volume monitor

OBJECTIVE: Bladder volume monitors may be useful for surveillance of bladder volume and urine production in urologic patients. Therefore, we designed an ultrasonic bladder volume monitor and evaluated it in vitro using phantoms and in vivo in one male volunteer. The purpose of this study was to perform a more thorough in vivo evaluation of our monitor in urologic patients to investigate biological effects and variance over a wide range of bladder volumes. MATERIAL AND METHODS: Thirty urologic patients of either gender were examined using the bladder volume monitor, which is based on seven phased array ultrasonic transducers arranged in a circular pattern to optimize detection of the bladder walls. The monitor was set up to record bladder volume every 30 s during two sequential cystometries with infusion rates of 30 and 60 ml/min. The measured volumes were analyzed using regression analysis to determine volume increments (slopes), offset volume (intercept) and correlation (Pearson's correlation coefficient). RESULTS: In the male patients, the median correlation coefficient between the infused and measured volumes was 0.97 and the slope was 0.68 ml/ml, thus warranting a correction factor of approximately 1.47 with no general volume offset. In the female patients, small bladders were generally outside the field of view of the monitor. Consequently, the correlation coefficients and slopes were 0.834 (median) and 0.43 (mean), respectively, whereas volume offsets were generally negative. CONCLUSIONS: For examinations in male patients, the performance of the bladder volume monitor was adequate. However, for examinations in female patients, a minor redesign of the transducer unit is necessary to insure proper operation.     

Total and regional fat distribution is strongly influenced by genetic factors in young and elderly twins

OBJECTIVE: Indirect estimates of obesity such as BMI seem to be strongly influenced by genetic factors in twins. Precise measurements of total and regional fat as determined by direct techniques such as DXA scan have only been applied in a few twin studies. The aim of the present study was to estimate the heritability (h(2)) of total and regional fat distribution in young and elderly Danish twins. RESEARCH METHODS AND PROCEDURES: Monozygotic (108) and dizygotic (88) twins in two age groups (25 to 32 and 58 to 66 years) underwent anthropometric measurements and DXA scans. Intraclass correlations and etiologic components of variance were estimated for total and regional fat percentages using biometric modeling. RESULTS: The intraclass correlations demonstrated higher correlations for all fat percentages among monozygotic twins as compared with dizygotic twins. The biometric modeling revealed a major genetic component (h(2)) of total (h(2)(young) = 0.83, h(2)(elderly) = 0.86) and regional fat percentages (trunk, h(2)(young) = 0.82, h(2)(elderly) = 0.85; lower body, h(2)(young) = 0.83, h(2)(elderly) = 0.81; and trunk/lower body, h(2)(young) = 0.83, h(2)(elderly) = 0.71) in both the young and elderly twins. DISCUSSION: The h(2) estimates emphasize that body fat and distribution as determined by DXA scan are under extensive genetic control.     

Bullying and symptoms among school-aged children: international comparative cross sectional study in 28 countries

BACKGROUND: There have been no large-scale international comparisons on bullying and health among adolescents. This study examined the association between bullying and physical and psychological symptoms among adolescents in 28 countries. METHODS: This international cross-sectional survey included 123,227 students 11, 13 and 15 years of age from a nationally representative sample of schools in 28 countries in Europe and North America in 1997-98.The main outcome measures were physical and psychological symptoms. RESULTS: The proportion of students being bullied varied enormously across countries. The lowest prevalence was observed among girls in Sweden (6.3%, 95% CI: 5.2-7.4), the highest among boys in Lithuania (41.4%, 95% CI 39.4-43.5). The risk of high symptom load increased with increasing exposure to bullying in all countries. In pooled analyses, with sex stratified multilevel logistic models adjusted for age, family affluence and country the odds ratios for symptoms among students who were bullied weekly ranged from 1.83 (95% CI 1.70-1.97) to 2.11 (95% CI 1.95-2.29) for physical symptoms (headache, stomach ache, backache, dizziness) and from 1.67 (95% CI 1.55-1.78) to 7.47 (95% CI 6.87-8.13) for psychological symptoms (bad temper, feeling nervous, feeling low, difficulties in getting to sleep, morning tiredness, feeling left out, loneliness, helplessness). CONCLUSION: There was a consistent, strong and graded association between bullying and each of 12 physical and psychological symptoms among adolescents in all 28 countries.     

Biological tissue adhesive for mesh-application in pigs: An experimental study

Background Tissue damage during herniotomy may attribute to postoperative complications including chronic pain, bleeding and infection. Thus the aim of this study was to evaluate a due and simple operative procedure with intraperitoneal application of mesh with glue in an experimental model prior to use in humans.Method Laparoscopic insertion of a mesh was performed in three pigs. The meshes were fixed with a collagen glue. The pigs were sacrificed after 8 weeks and macroscopic and microscopic evaluation of the meshes, were performed.Results The intraperitoneal placed meshes did not migrate through the study period, and there was no sign of inflammation in surrounding tissue or adhesions around the meshes.Conclusions If these findings can be applied to human inguinal herniotomy, this may lead to significant fewer complications including development of acute and chronic pain, formation of seroma and infection. Furthermore the operation technique is very simple.     

Interleukin-6 and diabetes: the good, the bad, or the indifferent?

Inflammatory mechanisms play a key role in the pathogenesis of type 1 diabetes. Individuals who progress to type 2 diabetes display features of low-grade inflammation years in advance of disease onset. This low-grade inflammation has been proposed to be involved in the pathogenetic processes causing type 2 diabetes. Mediators of inflammation such as tumor necrosis factor-alpha, interleukin (IL)-1beta, the IL-6 family of cytokines, IL-18, and certain chemokines have been proposed to be involved in the events causing both forms of diabetes. IL-6 has in addition to its immunoregulatory actions been proposed to affect glucose homeostasis and metabolism directly and indirectly by action on skeletal muscle cells, adipocytes, hepatocytes, pancreatic beta-cells, and neuroendocrine cells. Here we argue that IL-6 action-in part regulated by variance in the IL-6 and IL-6alpha receptor genes-contributes to, but is probably neither necessary nor sufficient for, the development of both type 1 and type 2 diabetes. Thus, the two types of diabetes are also in this respect less apart than apparent. However, the mechanisms are not clear, and we therefore propose future directions for studies in this field.