Lung cancer and exposure to man-made vitreous fibers: results from a pooled case-control study in Germany

BACKGROUND: To investigate the association between lung cancer and occupational exposure to man-made vitreous fibers (MMVF), a pooled analysis of two case-control studies was conducted in the years 1988-1994. METHODS: The case series consisted of 3498 males who were histologically or cytologically verified primary lung cancer cases. 3541 male population controls were drawn at random from the general population and matched to cases by sex, age, and place of residence. To examine the relationship between MMVF and lung cancer we asked all study subjects who worked for at least 6 months as construction and installation workers whether they ever installed or removed insulations and what kind of insulation material they used. RESULTS: Some 304 (8.7%) cases and 170 (4.8%) controls reported to have insulated with glass wool or mineral wool mats. Coded as ever/never exposed, the odds ratio was 1.48 (95% CI: 1.17-1.88), adjusted for smoking and asbestos. To be sure to exclude any confounding effect of asbestos, we tried to identify those cases and controls who insulated with glass wool or mineral wool mats only and never reported any asbestos exposure. For this group we calculated an odds ratio of 1.56 (95% CI: 0.92-2.65), after adjustment for smoking. An elevated risk was also estimated on the basis of an expert rating which was done for a subgroup of cases and controls. Ever exposure to MMVF (but not to asbestos) in this subgroup yielded an odds ratio of 1.30 (95% CI: 0.82-2.07). CONCLUSIONS: Our study provides some indication for an excess risk of man-made vitreous fibers. This result also persists after adjustment for smoking and asbestos.     

Lung cancer risk of workers in shoe manufacture and repair

BACKGROUND: The occupational lung cancer risk in manufacturing and repair of shoes was studied by pooling of two major case-control studies from Germany. METHODS: Some 4184 incident hospital-based cases of primary lung cancer and 4253 population controls, matched for sex, age, and region of residence were intensively interviewed with respect to their occupational and smoking history. Based on the occupational coding and a free text search, all individuals who had ever worked in shoe manufacturing or repair for at least half a year were identified. Shoemaker-years were calculated as the cumulated duration of working in shoe manufacturing or repair. Odds ratios (OR) and 95% confidence intervals (CI) were calculated via conditional logistic regression. Additional adjustment for smoking and occupational asbestos exposure was used. RESULTS: Seventy-six cases and 42 controls who had ever worked in shoe manufacture or repair (OR = 1.89, 95% CI: 1.29-2.78). After adjustment for smoking, this risk was lowered to 1.69 (95% CI: 1.09-2.62). Further adjustment for asbestos exposure only slightly changed the risk estimates upwards. The smoking adjusted OR in males was 1.50 (95% CI: 0.93-2.41) and 2.91 (95% CI: 0.90-9.44) in females. Logistic regression modeling showed a positive dose-effect relationship between duration of exposure in shoe manufacture and repair and lung cancer risk. The odds ratio for 30 years of exposure varied between 1.98 and 2.24 depending on the model specified. CONCLUSIONS: The study demonstrates an increased lung cancer risk for shoemakers and workers in shoe manufacturing. The risk seems to double after being 30 years in these occupations.     

Pharmacological alterations of coronary collateral circulation; Implication to the steal-phenomenon

Measurements of resistances were performed on different parts of coronary vessels, including spontaneous collaterals in anesthetized dogs, following ligation and embolization of the descending branch of the left coronary artery. The normal situation was compared with the state of maximal pharmacological dilatation.The pharmacological dilatation decreased the collateral resistance by 24% in spite of the fact that the collaterals supplied an infarcted area in this case; the precollateral resistance, which chiefly consists of large vessels was also diminished.The collateral perfusion pressure is not only dependent on the aortic pressure, but also on the flow rate in the corresponding large coronary vessel and thereby on the ratio of precollateral to postcollateral resistance.A decrease of the collateral perfusion pressure causes an insufficient perfusion of the area supplied by the collaterals only when the pressure fall is not compensated for by an adequate decrease in the collateral resistance and when the ratio of the collateral to the nutritive resistance increases. Thus, both, the extent of the pressure fall across the precollateral resistance and the dilating capacity of the collaterals determine whether or not a pharmacological dilatation of the coronary vascular bed results in an insufficient supply of an infarcted area, i.e. in a so called Steal-phenomenon.The results show further, that the given physical model of the microcirculation satisfactorily approximates the observed behaviour of the vascular system.The paper was supported by the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 30, Düsseldorf     

Fünfte wissenschaftliche Sitzung. Sonntag,den 26. September 1948, 11 Uhr.

Ohne Zusammenfassung     

Pathophysiology of parkinsonism.

The motor signs of Parkinson's disease are thought to result in large part from a reduction of the level of dopamine in the basal ganglia. Over the last few years, many of the functional and anatomical consequences of dopamine loss in these structures have been identified, both in the basal ganglia and in related areas in thalamus and cortex. This knowledge has contributed significantly to our understanding of the link between the degeneration of dopamine neurons in the midbrain and the development of parkinsonism. This review discusses the evidence that implicates electrophysiologic changes (including altered discharge rates, increased incidence of burst firing, interneuronal synchrony, oscillatory activity, and altered sensorimotor processing) in basal ganglia, thalamus, and cortex, in parkinsonism. From these studies, parkinsonism emerges as a complex network disorder, in which abnormal activity in groups of neurons in the basal ganglia strongly affects the excitability, oscillatory activity, synchrony and sensory responses of areas of the cerebral cortex that are involved in the planning and execution of movement, as well as in executive, limbic or sensory functions. Detailed knowledge of these changes will help us to develop more effective and specific symptomatic treatments for patients with Parkinson's disease.     

Epidemiology and cost of herpes zoster and postherpetic neuralgia in Germany

After acquiring a varicella virus infection, the virus can reactivate and cause herpes zoster (HZ)—a painful skin rash. A complication of HZ is long-term persistence of pain after the rash has resolved (so-called postherpetic neuralgia, PHN). We aimed to describe the epidemiology of HZ/PHN and to estimate HZ/PHN-related costs in the German statutory health insurance (SHI) system (~85 % of the total population). Treatment data of one large SHI was utilized, containing data on approximately 240,000 insured and their utilisation of services in 2004–2009. Identification of HZ- and PHN-cases was performed based on ‘International Statistical Classification of Diseases’ and specific medications using a control-group design. Incidences per 1,000 person-years (PY) and cost-of-illness for 1 year following HZ-onset considering the payer and societal perspective were calculated. All amounts were inflated to 2010 Euros. Population-figures were standardised and extrapolated to the total SHI-population in Germany in 2010. A mean annual incidence of 5.79 HZ-cases per 1,000 PY was observed, translating into an estimated 403,625 HZ-cases per year in the total SHI-population. Approximately 5 % of HZ-cases developed PHN. One HZ-case caused on average €210 and €376 of costs from the payer and societal perspective, respectively. The development of PHN generated additional costs of €1,123 (€1,645 societal perspective). Total annual HZ/PHN-related costs were estimated at €182 million (€105 million) to society (payer). HZ and PHN place a considerable burden on the German SHI-system. Since HZ-vaccines will soon be available, a health-economic evaluation of these vaccines should be conducted.     

Cost of dengue and other febrile illnesses to households in rural Cambodia: a prospective community-based case-control study

Background  

The average annual reported dengue incidence in Cambodia is 3.3/1,000 among children < 15 years of age (2002–2007). To estimate the economic burden of dengue, accurate cost-of-illness data are essential. We conducted a prospective, community-based, matched case-control study to assess the cost and impact of an episode of dengue fever and other febrile illness on households in rural Cambodia.     

Nullbeteiligungsgesellschaften

Ohne Zusammenfassung     

Synthesis and in vivo evaluation of [C]methyl-Ro 64-6198 as an ORL1 receptor imaging agent

(1S,3aS)-8-(2,3,3a,4,5,6-Hexahydro-1H-phenalen-1-yl)-3-N-[¹¹C]methyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-one ([¹¹C]methyl-Ro 64-6198), a N-methylated analog of Ro 64-6198, was synthesized and evaluated as a potential radiopharmaceutical for investigating brain nociceptin/orphanin FQ receptors (ORL1 receptors) by positron emission tomography. A racemate of methyl-Ro 64-6198, Ro 66-7931, showed a high affinity and selectivity for the ORL1 receptor in vitro. An in vivo distribution study in mice demonstrated moderate brain uptake, however, only slight difference was observed among brain regions. Furthermore, pretreating with nociceptin or Ro 66-7931 did not affect the accumulation. Therefore, despite its high affinity, [¹¹C]methyl-Ro 64-6198 does not appear to be a suitable tracer for in vivo ORL1 receptor imaging studies.     

Sex differences in stress responses: Focus on ovarian hormones

Women in the reproductive age are more vulnerable to develop affective disorders than men. This difference may attribute to anatomical differences, hormonal influences and environmental factors such as stress. However, the higher prevalence in women normalizes once menopause is established, suggesting that ovarian hormones may play an important role in the development of depression in women. Ovarian hormones such as estrogen can pass the brain-blood barrier and bind to cytoplasmatic estrogen receptor (ER)-alpha and ER-beta in different areas of the limbic system. During stress, estrogen can modulate the behavioral and neurobiological response depending on the concentrations of estrogen. In this review we present evidence for disparate effects of chronic stress on neuroplasticity and brain activity in male and female rats. Furthermore, we will demonstrate that effects of social support on coping with stress can be mimicked by social housing of rats and that this model can be used for identification of underlying neurobiological mechanisms, including behavior, phosphorylation of CREB and ERK1/2, and brain activity changes as measured with fos expression. Using cyclic administration of estrogen in ovariectomized female rats we could specifically address effects of different plasma estrogen levels and antidepressants on stress-induced neuroplasticity and activity changes. In this model we also studied effects of estrogen on recovery after chronic stress. We conclude that the female brain has a different innate strategy to handle stress than the male brain and that female animal models are necessary for studying the underlying mechanisms and options for treatment.