Immunorecognition of chondrocytes in articular cartilage activated by synovial interleukin 1.

A polyclonal antiserum which recognizes surface epitopes on IL1-activated pig chondrocytes has been used to immunolocalize chondrocytes responding to IL1 produced during co-culture of pig synovium and articular cartilage. Activation of the chondrocytes by the cytokine was restricted to the articular and subarticular region of the cartilage adjacent to the synovium. Chondrocyte activation was also seen when human rheumatoid synovium was co-cultured with the cartilage. The presence of IL1 in some synovial cells was confirmed by immunolocalization using antisera specific for IL1 alpha and IL1 beta.     

Tyramine-Induced cardiac arrhythmias

Five out of 12 physically healthy patients with depression undergoing a tyramine pressor test developed cardiac arrhythmias. These arrhythmias occurred in drug-free patients in three out of 12 infusions following as little as 0.03 mg/kg of tyramine and after moclobemide, a reversible inhibitor of monoamine oxidase-A, in four out of 14 tyramine infusions with as little as 0.04 mg/kg of tyramine. The arrhythmias seen were independent of patient's age and occurred both before and after 30 mmHg elevations in systolic blood pressure. Electrocardiographic abnormalities and arrhythmias seen were a loss of p waves, sinus tachycardia, frequent atrial ectopic beats, atrial premature beats, Wenckebach phenomenon, junctional rhythm, ventricular ectopics, varying QRS configurations, and ventricular bigeminy. Tyramine, both oral and intravenous, caused similar reproducible changes in dogs, though not in rats, mice or guinea pigs. Practical implications are that tyramine pressor testing in humans should be performed cautiously and only with adequate cardiac monitoring and resuscitation facilities at hand. These findings suggest that a normal dietary component can induce serious cardiac arrhythmias, and that a low-tyramine diet may be of value for patients who are susceptible to cardiac arrhythmias.     

Urothelial grafts in mice

Mouse bladder epithelium has been successfully transplanted to the bladders of syngeneic mice and has survived for at least twenty weeks. The fate of the transplanted tissue was followed using a fluorescein label. The recipient bladders were prepared by stripping the urothelium either by a surgical or a chemical method. The possibility of adopting a comparable technique for the treatment of early bladder cancer in man is discussed.     

A survey of the current methods used in the UK to assess pituitary function.

A national survey of the current methods used by specialists to evaluate pituitary function in the UK was performed by postal questionnaire. Seventy-three respondents, of whom 89% were consultants and 80% clinical endocrinologists, returned the questionnaire. Fifty per cent routinely used the insulin stress test (IST) to evaluate the hypothalamo-pituitary-adrenal (HPA) axis, while 50% routinely used tetracosactrin stimulation, there being little overlap between the two groups. This represents a significant change in clinical practice since the last survey in 1988. In those who used ACTH stimulation there was almost an equal split into those who administered the tetracosactrin intramuscularly (45%) or intravenously (47%). Furthermore, either the peak or 60 min cortisol value was used by 71% when interpreting the result of the test, despite the fact that in previous studies only the 30 min cortisol value has been shown to correlate with the IST result. The IST remains the most frequently used method to assess growth hormone reserve in adult subjects. The thyrotrophin-releasing-hormone and gonadotrophin-releasing-hormone tests are still used routinely by approximately a quarter of clinicians. These results provide data that could be used to develop guide-lines for the use of tests to investigate pituitary function.     

Parental perception of neonatal intensive care in public sector hospitals in South Africa.

BACKGROUND: Little is known about parental experience and decision making with regard to premature infants requiring intensive care in developing countries. We undertook this study to characterise parents' experience of physician counselling and their role in making life-support decisions for very low-birth-weight (VLBW) (birth weight < 1 501 g) infants born in South Africa's public-sector neonatal intensive care units (NICUs). METHODS: Parents of surviving VLBW infants treated in three Johannesburg-area public hospitals and attending follow-up clinics in August 2001 were interviewed regarding their experience of perinatal counselling on outcomes (pain, survival, disability), perception of actual and optimal decision making, and satisfaction with NICU communication. RESULTS: Parents of 51 infants were interviewed. Seventy-five per cent of parents reported antenatal counselling by physicians on at least one perinatal topic (severe disability, pain, death, finances or religious/moral considerations). The majority of parents (> 60%) who received counselling thought that these topics had been discussed adequately. Most parents reported that doctors had the primary decision-making role, either without consulting them (41%) or after consulting them (37%). Joint decision making was rare (14%). Parents wanted more input in life-support decisions than they reported being given. CONCLUSION: Counselling is not consistently provided in public-sector hospitals in Johannesburg. Parents of premature infants want a larger share in NICU decision making than they currently experience. Most parents were satisfied with communication later during their infant's hospitalisation. South Africa presents a unique opportunity to study the use of advanced medical technologies in a nation with marked disparities in access to care.     

The effect of ageing on the pharmacokinetics of dihydrocodeine

Summary Although poor renal function reduces clearance of dihydrocodeine in man, and renal impairment occurs with ageing, no significant differences occurred in the handling of single doses of dihydrocodeine between elderly patients and young, normal subjects.After multiple dosing, the maximum concentration was significantly different between the groups, being higher in the elderly. The increase in the area under the curve in the elderly was 25% greater than in the young on chronic therapy. This difference was not statistically significant, but was likely to be of clinical significance.The elderly patients' mean creatinine clearance (61.8 ml per min) was significantly lower than that in the young (137 ml per min), and there was a significant correlation between the half-life at single dosing and the blood urea concentration.Variability in all measurements was marked in both groups, and hence no clear guidelines can be given on therapeutic dosing. The small initial dose with alterations thereafter depending on clinical effect is the best advice.     

Catabolism of newly synthesized decorin in vitro by human peritoneal mesothelial cells.

OBJECTIVE: Previous studies have shown that decorin and biglycan account for over 70% of the proteoglycans (PGs) synthesized by human peritoneal mesothelial cells (HPMCs). Since these PGs are involved in the control of cell growth, cell differentiation, and matrix assembly, we investigated their turnover in cultured HPMCs. METHODS: Confluent HPMCs were metabolically labeled with [35S]-sulfate and the labeled products isolated from the cell medium and the cell layer characterized by sensitivity to bacterial eliminases. Experiments were undertaken with exogenous labeled decorin, and its metabolic state was studied. RESULTS: In a 24-hour labeling period, 75% of the newly synthesized chondroitin sulfate/dermatan sulfate (CS/DS) PGs appeared in the culture medium, the majority of which (90%) was decorin. In the cell layer, protein-free glycosaminoglycan (GAG) chains accounted for 21% of the total CS/DS at 24 hours and exhibited constant specific activity at 12-16 hours. The latter material was turned over with a half-life of approximately 2.5 hours. Exogenous decorin underwent receptor-mediated endocytosis and subsequent intracellular degradation. Uptake but not degradation could be inhibited by heparin. CONCLUSIONS: HPMCs are distinguished by a rapid turnover of decorin. A characteristic metabolic feature is the existence of a large intracellular pool of protein-free DS-GAGs. Understanding the control of decorin turnover in HPMCs might lead to delineation of its potential role in both the physiology and pathophysiology of the membrane in PD patients.     

Insulin resistance Type A and short 5th metacarpals.

BACKGROUND/AIMS: Insulin resistance is associated with a number genetic syndromes and a variety of defects of insulin action. METHODS: We describe three members of an extended family spanning two generations with insulin resistance Type A and short 5th metacarpals. The proband had secondary amenorrhoea, male pattern hair distribution, acne, hirsutism, deep voice, acanthosis nigricans, polycystic ovaries, diabetes, features of acromegaly, raised creatine kinase and triglyceride levels and short 5th metacarpals. Her growth hormone, adrenal steroid and testosterone levels were normal. The proband's daughter had severe acne, hirsutism, acanthosis nigricans, polycystic ovaries, raised triglyceride, glucose and testosterone level short metacarpals and normal insulin receptor gene. The proband's son had a muscular build, raised creatine kinase, hypertriglyceridaemia and short 5th metacarpals. His fasting insulin levels were normal but pro-insulin was raised. RESULT/CONCLUSION: There are many familial and genetic syndromes associated with insulin resistance. This family was diagnosed as having insulin resistance Type A. This family does not conform entirely to any of the previously described syndromes and a number of family members have the phenotype of short 5th metacarpals, which appears to be associated with the features of insulin resistance Type A.