Prostaglandin Endoperoxides IX. Characterization of Rabbit Aorta Contracting Substance (RCS) from Guinea Pig Lung and Human Platelets

Material causing contraction of the isolated rabbit aorta (rabbit aorta contracting substance, RCS) was released from guinea pig lung following perfusion with arachidonic acid and from human blood platelets after addition of thrombin to induce aggregation. Prostaglandin endoperoxides (prostaglandins G₂ and/or H₂) were found both in the perfusate of guinea pig lung (1–3 ng/ml) and in the medium collected after platelet aggregation (13–37 ng/ml). The contractile response of the isolated rabbit aorta to the pure prostaglandins G₂ and H₂, was also determined. These data combined with the quantitative analyses of the endoperoxides released from the lungs and platelets showed that only a minor part of the rabbit aorta contracting activity was due to the prostaglandin endoperoxides. The major part of the activity consisted of very unstable material. The half life of this material was about 30 s at 37d? whereas at this temperature the prostaglandin endoperoxides had a half life of about 5 min.     

Use of period analysis for providing more up-to-date estimates of long-term survival rates: empirical evaluation among 370,000 cancer patients in Finland

BACKGROUND: Providing up-to-date estimates of cancer patient survival rates is an important task of cancer registries. A few years ago, a new method of survival analysis, denoted period analysis, was proposed to enhance the recency of long-term survival estimates. The aim of this paper is to provide a comprehensive empirical evaluation of the use of this method. METHODS: Using data from the nationwide Finnish Cancer Registry, we compare 5-year and 10-year relative survival rates of 371 849 patients diagnosed with one of the 16 most common forms of cancer in Finland at various time intervals between 1953 and 1992 with the most up-to-date estimates of 5-year or 10-year relative survival that might have been obtained in those time intervals by traditional methods of survival analysis and by period analysis of survival. RESULTS: Survival rates strongly increased over time for most forms of cancer. For these cancers, traditional estimates of 5- and 10-year survival rates would have severely lagged behind the survival rates later observed for newly diagnosed patients, and period analysis would consistently have provided much more up-to-date estimates of survival rates. CONCLUSIONS: We conclude that period analysis should be implemented as a standard tool for providing up-to-date estimates of long-term survival rates by cancer registries.     

Inhalation of decomposed chlorodifluoromethane (freon-22) and myocardial infarction

After exposure to decomposed chlorodifluoromethane (freon-22), a 65-year-old man developed respiratory symptoms such as cough, blood-stained sputum, and increasing dyspnea. Three weeks later, his family doctor diagnosed infectious bronchitis. Another week later he died due to myocardial infarction. The discussion focuses on an inflammatory process caused by the inhalation of decomposed freon and its possible association with myocardial infarction.     

Alcohol intake and risk of non-Hodgkin lymphoma in men and women

Objective: The effect of alcohol intake on risk of NHL is unclear. We therefore conducted a population-based case-control study to examine the association between alcohol and NHL risk. Methods: 613 NHL cases and 480 population controls in Sweden reported their average consumption of beer, wine, and liquor 2years before the study. Unconditional logistic regression was used to estimate the odds ratios (OR) and corresponding 95% confidence intervals (CI) for associations between alcohol intake and NHL risk. Results: Intake of total alcohol, beer, wine, or liquor was not associated with risk of overall NHL. There was no difference in risk of NHL among those who habitually consumed above 19.1g of ethanol per day, compared to those who consumed on average 0–2.2g of ethanol per day (OR = 1.2 (95% CI: 0.8, 1.7); p _trend = 0.29). However, the association was significantly positive among males (OR = 1.8 (95% CI: 1.1, 2.9); p _trend = 0.06). Total alcohol, beer, wine, or liquor intake was not associated with any major histopathologic subtype of NHL examined, apart from an association between high wine consumption and increased risk of chronic lymphocytic leukemia. Conclusions: Alcohol does not appear to be a major etiologic factor for overall NHL, nor its common subtypes.     

Temporary preservation of beta-cell function by diazoxide treatment in childhood type 1 diabetes

OBJECTIVE: We examined the effect of diazoxide, an ATP-sensitive K(+) channel opener and inhibitor of insulin secretion, on beta-cell function and remission in children at clinical onset of type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 56 subjects (21 girls and 35 boys, age 7-17 years) were randomized to 3 months of active treatment (diazoxide 5-7.5 mg/kg in divided doses) or placebo in addition to multiple daily insulin injections and were followed for 2 years. RESULTS: Diazoxide decreased circulating C-peptide concentrations by approximately 50%. After cessation of the treatment, basal and meal-stimulated C-peptide concentrations increased to a maximum at 6 months, followed by a decline. Meal-stimulated C-peptide concentration was significantly higher at 12 months (0.43 +/- 0.22 vs. 0.31 +/- 0.26 nmol/l, P = 0.018) and tended to fall less from clinical onset to 24 months in the diazoxide- vs. placebo-treated patients (-0.05 +/- 0.24 vs. -0.18 +/- 0.26 nmol/l, P = 0.064). At 24 months, the meal-stimulated C-peptide concentrations were 0.24 +/- 0.20 and 0.20 +/- 0.17 nmol/l, respectively. Side effects of diazoxide were prevalent. CONCLUSIONS: This study demonstrates that partial inhibition of insulin secretion for 3 months at onset of childhood type 1 diabetes suspends the period of remission and temporarily preserves residual insulin production. Further evaluation of the full potential of beta-cell rest will require compounds with less side effects as well as protocols optimized for sustained secretory arrest.     

Substantial changes in life: perceptions in patients with newly diagnosed advanced cancer and their spouses

There are few studies on patients' perceptions of their situation after being recently diagnosed with an advanced gastrointestinal cancer and those of their spouses. Fourteen patients and their spouses were interviewed separately. The interviews were analyzed using a phenomenographic approach. The analysis indicated that the response categories for patients and spouses were roughly the same, but the number of patients and spouses who made statements differed between categories. All informants perceived substantial changes in life. This included negative physical, mental, and practical changes as well as positive changes. Mental changes included 3 categories: despair, why, and uncertainty. The informants described several ways of handling these changes in life. The most frequently reported by patients were that "one shouldn't complain" and by spouses to "hope," and by all informants to "make the best of it." Other ways of handling the situation were reconciliation, avoidance, preparation for death, seeking support, and isolation. In conclusion, more patients than spouses seemed to accept their situation because fewer patients complained and instead prepared for death, whereas more spouses felt despair, used hope and avoidance, and were preoccupied with practical matters. These findings suggest that spouses are a vulnerable group and healthcare staff should be just as aware of their situation as that of the patients.     

Akt activity in Alzheimer's disease and other neurodegenerative disorders

Enzyme activities of the serine/threonine kinase Akt were compared in mid-temporal and mid-frontal cortices from Alzheimer's disease cases and matched controls. Activities (GSK-3alpha/beta fusion protein phosphorylation by immunoprecipitated Akt) were significantly increased in temporal cortex soluble fractions from Alzheimer's disease compared with non-disease controls and positive disease controls with another neurodegenerative disease. Temporal cortex soluble fraction Akt activities positively correlated with Braak staging for neurofibrillary changes. Frontal cortex soluble fraction activities were significantly reduced in positive disease compared with Alzheimer's disease cases and non-disease controls. Strong Ser Akt immunoreactivity was seen in Alzheimer's disease pyramidal neurons likely undergoing degeneration and in reactive astroglia. Non-disease and positive disease controls showed moderate Ser Akt immunostaining of occasional pyramidal neurons.     

An active and socially integrated lifestyle in late life might protect against dementia

The recent availability of longitudinal data on the possible association of different lifestyles with dementia and Alzheimer's disease (AD) allow some preliminary conclusions on this topic. This review systematically analyses the published longitudinal studies exploring the effect of social network, physical leisure, and non-physical activity on cognition and dementia and then summarises the current evidence taking into account the limitations of the studies and the biological plausibility. For all three lifestyle components (social, mental, and physical), a beneficial effect on cognition and a protective effect against dementia are suggested. The three components seem to have common pathways, rather than specific mechanisms, which might converge within three major aetiological hypotheses for dementia and AD: the cognitive reserve hypothesis, the vascular hypothesis, and the stress hypothesis. Taking into account the accumulated evidence and the biological plausibility of these hypotheses, we conclude that an active and socially integrated lifestyle in late life protects against dementia and AD. Further research is necessary to better define the mechanisms of these associations and better delineate preventive and therapeutic strategies.     

Neuronal expression of caspase-1 immunoreactivity in the rat central nervous system

Caspase-1/interleukin-1beta (IL-1beta)-converting enzyme (ICE) cleaves IL-1beta and IL-18 precursor proteins to the active forms of these proinflammatory cytokines. Since both cytokines are constitutively expressed in the brain, we investigated whether this is also the case for caspase-1. Using an antibody raised against the p10-subunit of the active enzyme, constitutive expression of caspase-1 immunoreactivity was found in nerve cells in the arcuate nucleus and in nerve fibres throughout the brain. Co-localisation with alpha-melanocyte stimulating hormone was demonstrated. The distribution pattern of caspase-1 immunoreactive structures is consistent with a role to produce mature IL-1beta in regions where IL-1beta mediates fever and sleep.