Diet and premenopausal bilateral breast cancer: A case-control study

We investigated associations between diet and premenopausal bilateral breast cancer in a familial matched case-control study. We studied 140 cases from population-based registries in Los Angeles County (California) and Connecticut, and from the major hospitals in the southern parts of the Province of Quebec. Unaffected sisters of the cases served as matched controls (222 total). Dietary intake were assessed with a food frequency questionnaire. Total fat, monounsaturated fat, polyunsaturated fat, oleic acid, and linoleic acid intake was inversely associated with premenopausal bilateral breast cancer risk. Consumption of carbohydrates (and sweetened beverages) was associated with an increased risk. We observed no associations for dietary fiber, antioxidants, or major food groupings, but we did observe inverse associations for intake of low fat dairy products and tofu. These findings suggest that monounsaturated and polyunsaturated fats, as well as soy foods, might reduce the risk of premenopausal bilateral breast cancer.     

Possible heterogeneity in the segregation pattern of breast cancer in families with bilateral breast cancer

We investigated the segregation pattern of breast cancer in families with bilateral breast cancer, classifying families with respect to menopausal status (premenopausal versus postmenopausal) and the interval between diagnosis of the two primary tumors in the probands. Probands were "synchronous" if both primaries were diagnosed within 1 year; "asynchronous" if the interval was at least 2 years. Results for four complex segregation analyses are here presented; the findings support heterogeneity in the transmission of breast cancer. In the asynchronous premenopausal-cases-only analysis, a dominant Mendelian gene can explain the breast cancer pattern. A recessive gene is sufficient to describe the breast cancer distribution in the synchronous premenopausal-cases-only analysis. The synchronous all-cases and the asynchronous all-cases analyses add postmenopausal cases of breast cancer to the premenopausal ones, considering any case to be affected. In the asynchronous all-cases analysis, neither the single-locus model nor the mixed model (that is, a major locus plus other factors, genetic and/or cultural) without generation differences in heritability can be rejected by the unrestricted mixed model with generation differences in heritability. For the synchronous all-cases analysis, a mixed model with generation differences in heritability is necessary to explain the breast cancer transmission. Potential sources of error and possible interpretations are discussed.     

A reappraisal of time trends in ulcer disease: factors related to changes in ulcer hospitalization and mortality rates.

There has been a dramatic decline in reported hospitalization and mortality rates for peptic ulcer disease in the past two decades. Data from the National Center for Health Statistics and from the Commission on Professional and Hospital Activities were examined to determine the cause(s) for this decline. Gastric and duodenal ulcer mortality rates decreased by 58 per cent and 68 per cent, respectively, from 1962 to 1978; changes in criteria for selecting the underlying cause of death might account for some of this apparent decrease. Hospitalization rates for duodenal ulcers decreased nearly 50 per cent from 1970 to 1978, but hospitalizations for gastric ulcers did not decrease. During this same time period, hospitalizations for peptic ulcers as one of the "all listed" causes remained stable, and hospitalizations for a closely related diagnosis, gastritis/duodenitis, increased. Changes in coding practices, hospitalization criteria, and diagnostic procedures appear to have contributed to the decline in reported hospitalization and mortality rates for peptic ulcer disease.     

Analyse des Vorganges der Methylalkoholvergiftung auf Grund des pathologisch-anatomischen Bildes

Zusammenfassung Die morphologische Analyse einer Gruppenvergiftung mit Methylalkohol zeitigt Befunde, die sich in Capillar- und Parenchymschäden ä ußern.Auf Grund dieser Analyse wird das Zustandekommen der Methylalkoholvergiftung zu deuten versucht. Nach Besprechung der Toxikologie des Methylalkohol und der in der Literatur erschienenen Fälle von Methylalkoholvergiftung, die nur graduelle, aber keine grundsätzlichen Abweichungen von den eigenen Untersuchungen ergeben, wird das Schicksal des Methylalkohol im. Körper erörtert, wobei die chemischen Untersuchungsergebnisse des eigenen Materials wichtige Anhaltspunkte geben.Das Wesen der tödlich verlaufenden Methylalkoholvergiftung wird in einer Störung des Capillargefä ßsystems, also in einer unspezifischen Äußerung erblickt. Die Parenchymschäden resultieren aus derselben.Über die Ursache der Capillarstörung bei der Methylalkoholvergiftung läßt sich heute noch nichts Bestimmtes aussagen. Sicher erscheint uns zu sein, daß das bei der Oxydation entstehende Form-aldehyd die Capillaren mehr indirekt als direkt, d. h. von der Blutbahn aus schädigt. Der Rolle des Formaldehyd bei Methylalkoholvergiftung ist trotz der fehlenden Nachweisbarkeit der durch dasselbe gesetzten Schädigung eine große Bedeutung zuzumessen. Der zentral ausgelöste Tod kann nur als Folge des Formaldehyd betrachtet werden.     

The Protective Effects of Up-Regulating Prostacyclin Biosynthesis on Neuron Survival in Hippocampus

Cellular arachidonic acid (AA), an unsaturated fatty acid found ubiquitously in plasma membranes, is metabolized to different prostanoids, such as prostacyclin (PGI₂) and prostaglandin E₂ (PGE₂), by the three-step reactions coupling the upstream cyclooxygenase (COX) isoforms (COX-1 and COX-2) with the corresponding individual downstream synthases. While the vascular actions of these prostanoids are well-characterized, their specific roles in the hippocampus, a major brain area for memory, are poorly understood. The major obstacle for its understanding in the brain was to mimic the biosynthesis of each prostanoid. To solve the problem, we utilized Single-Chain Hybrid Enzyme Complexes (SCHECs), which could successfully control cellular AA metabolites to the desired PGI₂ or PGE₂. Our in vitro studies suggested that neurons with higher PGI₂ content and lower PGE₂ content exhibited survival protection and resistance to Amyloid-β-induced neurotoxicity. Further extending to an in vivo model, the hybrid of PGI₂-producing transgenic mice and Alzheimer’s disease (AD) mice showed restored long-term memory. These findings suggested that the vascular prostanoids, PGI₂ and PGE₂, exerted significant regulatory influences on neuronal protection (by PGI₂), or damage (by PGE₂) in the hippocampus, and raised a concern that the wide uses of aspirin in cardiovascular diseases may exert negative impacts on neurodegenerative protection.

Our study intended to understand the crosstalk of prostanoids in the hippocampus, a major brain area impacted in AD, by using hybrid enzymes to redirect the synthesis of prostanoids to PGE₂ and PGI₂, respectively. Our data indicated that during inflammation, the vascular mediators, PGI₂ and PGE₂, exerted significant regulatory influences on neuronal protection (by PGI₂), or damage (by PGE₂) in the hippocampus. These findings also raised a concern that the widely uses of non-steroidal anti-inflammatory drugs in cardiovascular diseases may exert negative impacts on neurodegenerative protection.

     

Colorectal cancer in patients under close colonoscopic surveillance

BACKGROUND & AIMS: Colonoscopic polypectomy is considered effective for preventing colorectal cancer (CRC), but the incidence of cancer in patients under colonoscopic surveillance has rarely been investigated. We determined the incidence of CRC in patients under colonoscopic surveillance and examined the circumstances and risk factors for CRC and adenoma with high-grade dysplasia. METHODS: Patients were drawn from 3 adenoma chemoprevention trials. All underwent baseline colonoscopy with removal of at least one adenoma and were deemed free of remaining lesions. We identified patients subsequently diagnosed with invasive cancer or adenoma with high-grade dysplasia. The timing, location, and outcome of all cases of cancer and high-grade dysplasia identified are described and risks associated with their development explored. RESULTS: CRC was diagnosed in 19 of the 2915 patients over a mean follow-up of 3.7 years (incidence, 1.74 cancers/1000 person-years). The cancers were located in all regions of the colon; 10 were at or proximal to the hepatic flexure. Although most of the cancers (84%) were of early stage, 2 participants died of CRC. Seven patients were diagnosed with adenoma with high-grade dysplasia during follow-up. Older patients and those with a history of more adenomas were at higher risk of being diagnosed with invasive cancer or adenoma with high-grade dysplasia. CONCLUSIONS: CRC is diagnosed in a clinically important proportion of patients following complete colonoscopy and polypectomy. More precise and representative estimates of CRC incidence and death among patients undergoing surveillance examinations are needed.