A man's reach should exceed his grasp. The 1988 Philip Nichols Memorial Lecture.

Dr P. J. R.

Strain-dependency of procarbazine-induced testicular toxicity.

Three strains of rat were used to examine strain-dependency of procarbazine-induced testicular toxicity. CCFHB and CCFY1 outbred albino rats and inbred PVG piebald variegated rats were treated weekly with procarbazine (200 mg/kg/dose x 4). Fifty-six days later, the rats were killed and reproductive parameters evaluated.

Myocardial infarction: a complication of amitriptyline overdose.

A 22 year old woman was admitted with amitriptyline overdose. Twenty six hours later she developed acute myocardial infarction. Cardiotoxic effects of tricyclic antidepressants are discussed and the importance of considering myocardial infarction as a complication of tricyclic antidepressant overdose is emphasized.

Proximal femoral fractures: some determinants of outcome.

We identified 226 proximal femoral fractures prospectively in people aged over 60 years during one year in Stockport (population approximately 289,000). Our objective was to examine the association between primary treatment and outcome 6 months after the fracture using multivariate regression models. Higher haemoglobin concentrations and mental test scores on admission to hospital were associated with lower fatality within 6 months, whereas a high blood calcium-phosphate product, greater age, and an active medical problem at the time of the fracture were all associated with increased fatality.

Antibodies to type II and XI collagens: evidence for the formation of antigen specific as well as cross reacting antibodies in patients with rheumatoid arthritis.

Antigen specific and cross reacting antibodies to native and denatured types II and XI collagen were detected in the sera of rats immunised with either of these antigens. The antibodies from rats immunised with type XI collagen initially showed the strongest binding to the alpha 2(XI) chain of type XI collagen but later binding to the alpha 3(XI) chain was seen. Sera from patients with rheumatoid arthritis had antibodies that bound to both type II and XI collagens.

The diabetic foot.

Diabetic foot lesions most commonly result from a combination of neuropathy and vascular disease in the lower extremity, and may be the presenting feature of diabetes in the older patient. Insufficient attention previously has been given to the careful clinical assessment of the foot, which enables the physician to recognize those patients who are at particular risk of ulceration. The high-risk patient requires education and frequent follow up to reduce the risk of lesions developing.

Muscle adenosine 5'-triphosphate and creatine phosphate concentrations in relation to nutritional status and sepsis in man.

1. Intramuscular concentrations of adenosine 5'-triphosphate (ATP) and creatine phosphate were measured in the vastus lateralis muscle of 28 non-septic malnourished patients and 31 septic malnourished patients. Similar measurements were made on the rectus abdominis muscle of about one-third of these patients.

Functional and biosynthetic changes in endothelial cells of vessels in chronically inflamed tissues: evidence for endothelial control of lymphocyte entry into diseased tissues.

In vitro lymphocyte adhesion to, and selective radiosulphate uptake by, endothelial cells has been demonstrated in chronically inflamed tissues of patients with peptic ulceration, rheumatoid disease, pilonidal sinus, autoimmune thyroiditis, polymyositis, primary biliary cirrhosis, and pyelonephritis. These characteristics have been described previously in endothelial cells functionally specialized for promoting lymphocyte traffic from blood to lymph node parenchyma. It is suggested that these observations indicate that some vessels in inflamed tissues may be, at least in part, responsible for the selective accumulation of lymphocytes within the tissue.

Is intracellular pH a coupling factor in nutrient-stimulated pancreatic islets?

Intracellular pH (pHi) was monitored in dispersed pancreatic islet cells from rats using the fluorescent dye 2'7'bis-carboxyethyl-5'(6')-carboxyfluorescein. The addition of a weak acid (acetate, propionate or formate) provoked a rapid fall in pHi, corresponding to approximately 0.2 units, following by a slower return to the basal value.

Comparison of delayed-release 5-aminosalicylic acid (mesalazine) and sulfasalazine as maintenance treatment for patients with ulcerative colitis.

To assess the safety and efficacy of delayed-release mesalazine (5-aminosalicylic acid) as maintenance treatment for patients with ulcerative colitis, 100 patients with quiescent colitis were randomly grouped to receive either delayed-release mesalazine or an equivalent dose of enteric-coated sulfasalazine in a 48-wk trial. Groups were comparable for age, sex, and duration and extent of disease. Relapse rates at 48 wk were as follows: sulfasalazine 38.

Comparison of delayed release 5 aminosalicylic acid (mesalazine) and sulphasalazine in the treatment of mild to moderate ulcerative colitis relapse.

Oral formulations of 5-aminosalicylic acid (mesalazine) appear less toxic than sulphasalazine. We have therefore compared sulphasalazine, low dose mesalazine and high dose mesalazine in the treatment of mild to moderate relapse of ulcerative colitis. Sixty one patients (32 men, aged 20-78 years) were randomly allocated to sulphasalazine 2 g daily, mesalazine 800 mg daily, or mesalazine 2.

Left ventricular thrombosis in acute transmural myocardial infarction.

To determine the incidence and natural history of left ventricular thrombosis in acute transmural myocardial infarction we performed serial two-dimensional echocardiography in 51 patients. Seventeen patients had inferior infarcts. None of these developed left ventricular thrombosis.

Thermogenic effects of thyrotrophin-releasing hormone and its analogues in the rat.

Acute or chronic injection of RX 77,368 (a TRH analogue; 1 mg/kg s.c.) stimulated oxygen consumption (VO2) and brown adipose tissue activity in the rat, and decreased weight gain.

The Gemini conundrum--a problem of unpairable data: statistical comparison of ratios each derived from two separately estimated parameters.

In biological studies it may be necessary to compare ratios of two separately estimated parameters under test and control conditions. Since it is not always possible technically to obtain paired data for the two parameters, how does one take account of their variances? By extending previously described approximations in a modified t-test we present a BASIC computer program which may be used to solve this problem.

Mathematical and statistical analysis of circadian rhythms.

The mathematical and statistical analysis of biological time series is complex and often involves specialised techniques. In this article we review several of these techniques, placing particular emphasis on the usefulness, assumptions and kind of data that they require. Because classical methods of time series analysis often require long spans of data that are not frequently available in biological studies, particularly in clinical circumstances, several alternative techniques are described.

Racial inequalities in health: a challenge to the British National Health Service.

The existence of racial inequalities in health in the United Kingdom is examined using both indirect and direct data. The evidence strongly supports the view that the health experience of black and other ethnic minority groups is worse than that of the indigenous white population. Ways of improving this situation are outlined; they indicate the need for a coordinated Health service response incorporating planning, training, and equal opportunities in both service provision and employment practices.

Coming to terms with chronic illness: the negotiation of autonomy in rheumatoid arthritis.

This paper examines ways in which daily life is sustained in the face of chronic illness. Using data from interviews with people with rheumatoid arthritis, we try to capture the complexity of the interdependence between individuals with chronic illness and society. The main areas focused on cover the disordered body, disruption of relationships, and management of a deviant identity.

HEV-like vessels in lymphoid and non-lymphoid tissues.

High endothelial venules (HEV) are vessels characteristic of lymph nodes specialized for promoting lymphocyte migration between blood and the nodal parenchyma. The studies outlined in this article constitute an overview of work done in my laboratory to investigate some functional aspects of HEV and a group of venules that develop in sites in lymphocyte accumulation in non-lymphoid tissues which resemble HEV in many ways and are therefore known as HEV-like vessels. This is followed by a hypothesis to explain the development of HEV-like vessels and its importance for lymphocyte traffic.

A comparison of the morphological, histochemical and biochemical features of embryonic chick sternal chondrocytes in vivo with chondrocytes cultured in three-dimensional collagen gels.

Disaggregated chondrocytes from embryonic chick whole sterna proliferate in three-dimensional collagen gels forming mixtures of cartilage nodules (chondroids) and columns of cells. A typical matrix elaborated by the cells is composed of collagen type II and chondroitin and keratan sulphate proteoglycans. The cells of the chondroids are small and uniform whilst those in the columns are larger (hypertrophic) and have a vacuolated cytoplasm.

IgG subclass distribution of antinative type II collagen and antidenatured type II collagen antibodies in patients with rheumatoid arthritis.

In 81 patients with rheumatoid arthritis (RA) with antibodies to native type II collagen, the frequencies of each IgG subclass to native type II collagen were IgG1 (70%), IgG2 (12%), IgG3 (84%) and IgG4 (6%) and to denatured type II collagen were IgG1 (86%), IgG2 (23%), IgG3 (86%) and IgG4 (6%). Thus serum antibodies to type II collagen in patients with RA were predominantly of the complement fixing subclasses IgG1 and IgG3.

Individual and collective initiatives in disablement.

After setting a historical background for health care activities this paper relates the development of self-care to changes that have taken place. Relatively recent technological possibilities in medicine have altered the tensions in regard to self-care, highlighting demands for greater knowledge and the search for means of coming to terms with the existential challenge of chronic illness or disablement. The characteristics of self-help groups are discussed briefly, and problems are noted in relation to condition-specific orientation and the emphasis on personal identity and personal responsibility.

Increased procollagenase activating angiogenic factor in the vitreous humour of oxygen treated kittens.

Previous studies have demonstrated an increase in a low molecular weight angiogenic factor (ESAF) present in the retinae of kittens with oxygen induced retinopathy. The present paper describes differences in the quantity of ESAF extracted from the vitreous humour of control and oxygen treated animals and proposes a mechanism for the induction of intravitreal neovascularisation.