Risk factors for coronary heart disease mortality among persons with diabetes

Although synovial lining cells (SLC) have been implicated in the production of hyaluronan (HA), which is found at particularly high concentrations in synovial fluid, the degree to which individual cells within the synovium are adapted to this particular function remains to be elucidated. Uridine diphosphoglucose dehydrogenase (UDPGD) activity is the irreversible, rate-limiting step in the production of UDP-glucuronate, an essential monosaccharide in the synthesis of HA. We have assessed the UDPGD activity, microdensitometrically, in individual lining cells of normal and rheumatoid (RA) synovium, using a modified quantitative cytochemical method. In normal synovium, high activity was confined to the cells of the lining with negligible activity in the deeper subintima. The mean UDPGD activity/cell in lining cells of rheumatoid synovium was significantly lower than the activity in normal SLC. In some samples of RA and normal synovium, a bimodal distribution of cells was evident in the lining on the basis of UDPGD activity, a zone of cells in the basal layers with high UDPGD activity and a separate population of cells in more superficial layers with relatively low UDPGD activity. The results suggest that a particular population of cells is present, consistently in normal and more variably in RA synovial lining, which have high UDPGD activity/cell and may be involved in the production of HA. Furthermore, in RA synovium both the UDPGD activity/cell and the relative proportion of these cells within the lining appear to be decreased.     

Autoradiographic distribution and physiological regulation of 2-[125I]iodomelatonin binding in rat epididymis

Autoradiographic study was conducted to localize 2-[125I]iodomelatonin binding in the rat epididymis. In the peripubertal (6 weeks old), postpubertal (8 weeks old) and adult (3 months old) rats, intense specific 2-[125I]iodomelatonin labelling of the corpus epididymidis was observed. The intensity of 2-[125I]iodomelatonin binding in the distal epididymal segment was significantly decreased in orchidectomized rats but the effect could be reversed with testosterone replacement. The intensity of 2-[125I]iodomelatonin binding in the distal rat epididymal segment did not show any diurnal rhythmicity when mid-light period and mid-dark period levels were compared, and was unaffected by constant lighting. Our data suggest androgen-dependent expression of 2-[125I]iodomelatonin binding sites, independent of light-induced changes in circulating melatonin, in the rat corpus epididymidis. A novel role of melatonin and its receptor in the regulation of the functions of rat corpus epididymidis is strongly implicated.     

Axilloaxillary cardiopulmonary bypass: a practical alternative to femorofemoral bypass

BACKGROUND: Peripheral arterial and venous cannulation for cardiopulmonary bypass is used increasingly for patients undergoing minimally invasive cardiac operations, complex reoperations, or repair of aortic dissection or aneurysm, and for patients with extensive arteriosclerotic aortic disease in whom aortic cannulation is a prohibitive embolic risk. The common femoral artery and vein are most commonly used for peripheral cannulation, but these sites may be predisposed to complications, primarily because the femoral vessels are commonly involved with arteriosclerotic disease. We have recently begun to use the axillary artery and axillary vein as alternative cannulation sites, achieving full cardiopulmonary bypass, providing antegrade aortic flow, and avoiding many of the complications associated with other sites. METHODS: Seven patients with peripheral vascular or aortic disease, or both, prohibiting safe aortic or femoral cannulation underwent cardiopulmonary bypass through axillary artery and axillary vein cannulation, approached through a small single subclavicular incision. RESULTS: All patients were successfully cannulated and axilloaxillary cardiopulmonary bypass was possible without the need for additional cannulas. All axillary vessels were closed primarily without complication. CONCLUSION: For an expanding population of patients with peripheral vascular and aortic disease, axilloaxillary bypass is a safe and practical alternative to aortic or femoral cannulation.     

Promotion criteria for clinician-educators in the United States and Canada. A survey of promotion committee chairpersons

CONTEXT: Clinician-educators have concerns about their ability to be promoted and the criteria used by medical school promotion committees. OBJECTIVE: To discover the criteria and methods that medical school promotion committees use to make decisions about the promotion of clinician-educators. METHODS: In June 1996 we mailed a questionnaire to chairpersons of all medical school promotion committees in the United States and Canada. RESULTS: Of 142 schools surveyed, 115 (81%) responded; 45% of respondents had a clinician-educator promotion track. On a scale from 1 (minimally important) to 7 (extremely important), the mean importance ratings of aspects of clinician-educators' performance were the following: teaching skills (6.3), clinical skills (5.8), mentoring (5.7), academic administration (5.3), developing educational programs (5.3), nonresearch scholarship (5.1), clinical research (4.8), service coordination (4.7), and education research (4.5). Methods to evaluate each aspect of performance were rated by respondents for importance and frequency of use. The 4 most important methods for evaluating teaching were awards, peer evaluation, learner evaluation, and teaching portfolio; 70% or more of schools used these frequently or always. The 4 most important methods of evaluating clinical skills were peer evaluation, awards, trainee evaluation, and objective measures, which were used frequently or always by 78%, 65%, 58%, and 29% of schools, respectively. Clinician-educators were expected to have fewer peer-reviewed publications to be promoted than investigators (5.7 vs 10.6, P<.001). Schools with separate clinician-educator tracks differed little in survey responses from schools without such tracks. CONCLUSION: Most, but not all, promotion committees now assign high importance to the special contributions of clinician-educators and use a variety of methods to assess these, regardless of whether they have a separate clinician-educator promotion track.     

Aspirin-induced hepatic dysfunction in a patient with adult rheumatoid arthritis

A patient with classical rheumatoid arthritis receiving high doses of aspirin developed significant elevation of serum glutamic oxaloacetic transaminase. This patient had recently been on phenylbutazone and an initial liver biopsy, at the time of elevation of the transaminase revealed nonspecific mild fatty infiltration of the liver compatible with the pathology seen with rheumatoid disease. Because of the severity and activity of her rheumatoid arthritis, and thus the need to know whether aspirin was the etiologic factor in liver dysfunction, the patient was challenged with aspirin. SGOT elevation occurred after a 4-6 day lag period, which promptly remitted when salicylates were discontinued. A liver biopsy at this time revealed evidence for degeneration, regeneration, and mild focal mononuclear infiltration. Although previous reports note salicylate-related hepatocellular dysfunction in patients with systemic lupus erythematosus and juvenile rheumatoid arthritis, these data clearly demonstrate the relationship of ASA to liver dysfunction in a patient with adult onset rheumatoid arthritis. This histologic picture as well as the clinical course of this patient's hepatic abnormality suggest a toxic rather than hypersensitivity etiology for this syndrome.     

6-substituted 2,4-diamino-5-methylpyrido[2,3-d]pyrimidines as inhibitors of dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii and as antitumor agents

The synthesis and biological activity of 15 6-substituted 2,4-diamino-5-methylpyrido[2,3-d]-pyrimidines are reported. These compounds were synthesized in improved yields by modifications of procedures previously reported by us. Specifically, dimethoxyphenyl-substituted compounds with H and CH3 at the N-10 position and trimethoxyphenyl-substituted compounds with N-10 ethyl, isopropyl, and propargyl moieties were synthesized. These compounds were evaluated as inhibitors of dihydrofolate reductases (DHFR) from Pneumocystis carinii, Toxoplasma gondii, and rat liver, and selected analogues were evaluated as inhibitors of the growth of T. gondii and tumor cells in culture. All the compounds showed increased selectivity (vs rat liver DHFR) for T. gondii DHFR compared to trimetrexate. In general, for the trimethoxy-substituted analogues, increasing the size of the N-10 substituent from a methyl group to larger groups resulted in a decrease in selectivity and potency for both P. carinii and T. gondii DHFR. For the dimethoxy-substituted analogues, N-10 methylation in general decreased potency but increased selectivity for T. gondii DHFR. In an attempt to improve the cell penetration of these analogues, the N-10 naphthyl-substituted analogues were also synthesized. These analogues displayed excellent cell penetration and inhibition of T. gondii cells in culture. Further, these analogues were potent inhibitors of the growth of tumor cells in the preclinical in-vitro screening program of the National Cancer Institute with IC50s in the nanomolar range.     

Pinocytosis and intracellular digestion of 125I-labelled haemoglobin by trophoblastic cells in tissue culture in the presence and absence of serum

One aspect of human placental function which has not hitherto been studied is the ability of the placenta to digest proteins intracellularly and use the products of hydrolysis to supply its own and foetall complement of hydrolytic enzymes, including the acid proteases cathepsin C and D. We have used trophoblast cells in monolayer tissue culture as a model for the study of endocytosis and intracellular digestion of 125I-haemoglobin. The normal use of serum in tissue culture medium has shown up differences from the pattern observed with other phagocytic cells such as macrophages, in that serum allows endocytosis but prevents intracellular digestion of 125I-haemoglobin. Replacement of serum by lactalbumin hydrolysate enables both endocytosis and intracellular digestion of 125I-haemoglobin to occur as in other phagocytic cells. Digestion is followed by release into the medium of acid-soluble, lower-molecular-weight compounds. The reasons for this major difference between trophoblast and other cells are discussed in the light of our results and their possible relevance to placental function.     

Delinquency, institutionalization, and time orientation

Investigated the temporal orientation of delinquents and nondelinquents while adequately controlling institutionalization. Four groups of 17-25 yr old males ( N = 183) were selected: institutionalized delinquents (prison inmates), institutionalized nondelinquents (soldiers), noninstitutionalized delinquents (delinquents on probation), and noninstitutionalized nondelinquents (vocational students). Findings support most of the hypotheses: Although all Ss were basically future oriented, institutionalized Ss were more present oriented than their noninstitutionalized counterparts. As the prisoner approached release, there was a decrease in the salience of the present and an increase in the salience of the future in his life space. Delinquents (both in and out of prison) perceived the past as more negative and the future as more positive than did nondelinquents. Institutionalized Ss perceived the present as more negative than their noninstitutionalized counterparts. The affective attitudes of the nondelinquents toward the past, present, and future were much more balanced and realistic than that of the delinquents. (57 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fibrogenic potentials of coal slags used as abrasive blasting substitutes

This study was designed to examine the fibrogenic potentials of four coal slags that are being used as substitutes for silica sand in abrasive blasting. Six groups of 100 male Sprague-Dawley rats, including four coal slag groups, a vehicle control, and a positive control for fibrosis (Minusil quartz), were used. Each dust treatment group was given a single 40-mg dose of test agent via intratracheal instillation. Interim sacrifices of 15 animals per group were performed at 2 d, 3 mo, and 6 mo posttreatment, with the terminal sacrifice conducted at 12 mo. Hematoxylin and eosin stained histologic sections were prepared from designated formalin-fixed tissues collected at each necropsy and examined microscopically. Pulmonary silicon analyses were performed for each group at the 2-d and 12-mo sacrifices. Pulmonary function analyses were conducted for each group at the 3-, 6-, and 12-mo sacrifices. Lung hydroxyproline analyses were conducted for 15 animals in each group at the terminal sacrifice. The pulmonary fibrogenic potentials of the four coal slag groups were compared histologically with the Minusil and vehicle controls. A mild to moderate interstitial fibrosis, which was progressive with time, was noted in each of the coal slag groups. However, the coal slag-induced lung fibrosis was much less than that produced by Minusil. Differences in fibrosis among the individual coal slags were relatively minor and certainly not as striking as those between the slags and Minusil. Other data derived from this study, such as lung hydroxyproline content, pulmonary particulate burdens, pulmonary function, and animal body weights, provided further evidence of a reduced toxicity for the coal slags compared to Minusil.