Tumour dormancy: initiation, maintenance and termination in animals and humans

The authors review the natural occurrence of tumour dormancy in man and animal models, which show the importance of cellular defence mechanisms in inducing and maintaining the state of tumour dormancy. Six cases of non-small-cell lung cancer are described. The patients exhibited moderate to very strong delayed hypersensitivity reactions to soluble lung-cancer antigen after specific immunotherapy. Three patients had nonregional metastases at 11, 12 and 14 years. Two had regional recurrence after 9 years, and in one patient a small hilar-node metastasis was found at autopsy after 7.6 years. In each case an immunodepressive event or drug treatment preceded resurgent growth. The effect of renal transplantation in patients with a history of surgery for cancer supports the conclusion that cellular defence mechanisms are crucial for the maintenance of tumour dormancy in man.     

Structural and histochemical features of the avian blood-brain barrier

We have investigated the structural and histochemical features of the blood-brain barrier (b-bb) in both adults and embryos of chicken (Gallus domesticus, White Leghorn) and quail (Corturnix coturnix japonica). We found that brain endothelial cells of both species are characterized structurally by tight junctions, a low density of pinocytotic vesicles, and a moderately elevated density of mitochondria. Both alkaline phosphatase and butyryl cholinesterase were found in adult quail brain capillaries, but only alkaline phosphatase was found in adult chick brain capillaries. Aromatic amino acid decarboxylase was not found in brain capillaries of either species. In the chick embryo alkaline phsophatase appeared during the time when b-bb matures functionally; i.e., during the third week of development. However, an elevation in mitochondrial density was not apparent until after hatching. In the quail, alkaline phosphatase and butyrl cholinesterase appeared during the last week of embryonic development. By 2 days posthatching the structural characteristics of the brain capillaries were similar to those in the adult.     

Correlates of cognitive dysfunction in an ambulatory elderly population

Mini-Mental State Examination (MMSE) scores were studied in an ambulatory elderly population to identify correlates with self-reported signs, symptoms, diseases, drugs and laboratory values. A total of 1,264 subjects were studied including 844 women and 420 men. In this study, 5.0% of men and 5.3% of women scored less than 24 on the MMSE. A linear-regression model revealed eleven factors of significance in predicting scores on the MMSE. The most important predictors were age (p less than 0.0001), self-reported memory loss (p less than 0.0001), complaints of swollen feet or ankles (p less than 0.0010), the total number of diseases reported (0.0006) and the serum lactate dehydrogenase concentration (p less than 0.0098). Results suggest that cognitive function in the elderly is not related to the general level of health or consistently affected by specific disease states.     

Nitric oxide synthase inhibitor,nitro-iminoethyl-L-ornithine,reduces ischemia-reperfusion injury in rabbit skeletal muscle

Nitric oxide (NO), originally identified as the mediator of endothelial-dependent relaxation of vascular smooth muscle, is now known to also have cytotoxic effects under certain conditions. Thus, we have investigated the effects of inhibition of NO synthesis on ischemia/reperfusion injury in the rabbit rectus femoris muscle. Three and a half hours of ischemia and 24 hours of reperfusion resulted in a 56% loss of viability. In muscles receiving an infusion of the nitric oxide synthase inhibitor, L-NIO (30 μM), the loss of viability was reduced to 15%. Post-ischemic blood flow was increased in muscles receiving a saline infusion, whereas there was a marked decrease in blood flow for at least the first 60 minutes of reperfusion in muscles treated with L-NIO (30 μM). The increase in myeloperoxidase levels (indicative of neutrophil accumulation) following 24 hours of reperfusion was attenuated with L-NIO infusion by approximately 50% and the reperfusion-induced edema was also attenuated in L-NIO treated muscle. These findings suggest that endogenous NO production during ischemia/reperfusion injury may be deleterious to muscle survival. © 1994 Wiley-Liss, Inc.     

Gastro-oesophageal reflux disease: Medical or surgical treatment? Report of an interactive workshop

Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper.     

The functioning and well-being of depressed patients. Results from the Medical Outcomes Study

We describe the functioning and well-being of patients with depression, relative to patients with chronic medical conditions or no chronic conditions. Data are from 11,242 outpatients in three health care provision systems in three US sites. Patients with either current depressive disorder or depressive symptoms in the absence of disorder tended to have worse physical, social, and role functioning, worse perceived current health, and greater bodily pain than did patients with no chronic conditions. The poor functioning uniquely associated with depressive symptoms, with or without depressive disorder, was comparable with or worse than that uniquely associated with eight major chronic medical conditions. For example, the unique association of days in bed with depressive symptoms was significantly greater than the comparable association with hypertension, diabetes, and arthritis. Depression and chronic medical conditions had unique and additive effects on patient functioning.     

Indomethacin promotes germinal matrix microvessel maturation in the newborn beagle pup.

BACKGROUND AND PURPOSE: Although indomethacin has been demonstrated to prevent germinal matrix and intraventricular hemorrhage in clinical and animal studies, the mechanism of action of this agent to prevent hemorrhage remains unclear. Previous studies have demonstrated both that the microvessels in the germinal matrix of newborn beagle pups undergo basement membrane maturation during the first 4 postnatal days and that indomethacin may promote laminin deposition in tumor cell culture systems. METHODS: We employed the newborn beagle pup model to test the hypothesis that indomethacin may stimulate laminin deposition in germinal matrix microvessels. Newborn pups were randomized to receive either 0.1 mg/kg/dose i.p. indomethacin or an equal volume of saline diluent. Pups received doses of study medication once a day for 1, 2, or 3 days and were studied on postnatal days 1, 2, 3, or 4. Pups were anesthetized and systemically perfused with buffered formalin; the brains were removed and prepared for immunohistochemical study. RESULTS: Sections stained with Bandeiraea lectin demonstrated that there was no difference in germinal matrix vessel density among the postnatal ages studied; similarly, there were no differences in vessel density between saline- and indomethacin-treated animals at any postnatal age. Quantification of germinal matrix stained intensity by confocal microscopy demonstrated significant increases in indomethacin-treated pups for both laminin staining at postnatal days 2 (p = 0.05) and 3 (p = 0.0009) and type V collagen staining at postnatal day 2 (p = 0.011). Although staining for beta 1 integrins increased across postnatal ages, there were no differences between saline- and indomethacin-treated animals. CONCLUSIONS: These data suggest that indomethacin may stimulate basement membrane deposition in the germinal matrix microvessels of newborn beagle pups to prevent germinal matrix and/or intraventricular hemorrhage.     

Measurement of faecal ammonia.

A modified end-point enzymatic method for the measurement of ammonia in stool water is presented. A protein precipitation step was included in order to inactivate urease and faecal enzymes, which oxidise NADH. The modified method is reliable, with acceptable precision and accuracy, and is linear up to a concentration of 1.5 mmol/l.