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Biomedical subjects

M Hart

Publications and source records attributed to M Hart.

15 recordsLinked to original sources

Interleukin-8 in sepsis: relation to shock and inflammatory mediators.

Because of its neutrophil-activating properties, interleukin-8 (IL-8) may play an important role in the pathophysiology of sepsis. We measured circulating IL-8 levels in 47 patients with clinical sepsis. Levels on admission were elevated in 42 of the 47 patients (89%) and were comparable in patients with gram-positive or gram-negative infections. Patients with shock had significantly higher IL-8 levels than normotensive patients (P = 0.0014, Wilcoxon-Mann-Whitney test), whereas no differences in IL-8 levels were found between patients with or without adult respiratory distress syndrome. Patients who died had higher IL-8 levels on admission than the patients who survived. The largest differences in IL-8 levels between survivors and nonsurvivors was found when only patients with positive cultures were considered (P = 0.0342). IL-8 levels appeared to correlate significantly with lactate levels and inversely with leukocyte and platelet numbers and mean arterial pressure. In addition, the IL-8 level in the sepsis patients was found to correlate significantly with levels of IL-6, elastase-alpha 1-antitrypsin, and C3a. Serial observations revealed that in most patients IL-8 levels decreased, irrespective of the outcome. Thus, our results demonstrate that IL-8 levels are increased in most patients with sepsis and correlate with some important clinical, biochemical, and inflammatory parameters. These findings suggest a role for IL-8 in the pathophysiology of sepsis.

Adolescent

Occupational asthma in a beet sugar processing plant.

A patient with occupational asthma in the beet sugar processing industry is described. Symptomatology, skin testing, immunologic testing, and specific bronchoprovocation testing indicate exposure to moldy sugar beet pulp was the cause of the patient's occupational asthma. Cooperation between the treating physician and public health authorities is encouraged.

Adult

Twenty five years of case finding and audit in a socially deprived community.

OBJECTIVE: To evaluate audit and case finding (whole population care) in a community over 25 years. DESIGN: Contemporary screening for and audits of care of chronic disease and risk factors; retrospective review of computerised practice records; and comparisons of mortality and social indices with neighbouring communities. SETTING: One general practice in Glyncorrwg, West Glamorgan. SUBJECTS: 1800 people registered with the practice in 1987 and 558 people who died from 1964 to 1987, whose records had been retained. MAIN OUTCOME MEASURES: Detection of high blood pressure, smoking, airways obstruction, obesity, diabetes, and alcohol problems in adults aged 20-79; prevalence of smoking in this population and in hypertensive and diabetic groups; age standardised mortality ratios in relation to indices of social deprivation. RESULTS: In the population aged 20-79 (1207 patients) 249 (21%) had peak expiratory flow rate less than 50% of expected value or which improved by 15% or more with an inhaled beta agonist, 207 (17%) had body mass index at or over 30 kg/m2, 118 (10%) had untreated mean arterial pressures greater than 159/104 mm Hg (three readings), 80 (7%) (65 (16%) men, 15 (4%) women) had recognised alcohol problems, and 35 (3%) had diabetes. The proportion of men aged 20-64 who said they smoked fell from 61% (290/476) in 1968-70 to 36% (162/456) in 1985 whereas that of women who smoked was unchanged (43%, 187/436 v 42%, 190/448 respectively). In 116 screened hypertensive patients group mean blood pressure fell from 186/110 mm Hg before treatment to 146/84 mm Hg at 1987 audit, as did the proportion of smokers (56% v 20%), but body mass index and total cholesterol concentration showed no significant change. In 34 diabetic patients mean blood pressure and the proportion of smokers fell (171/93 mm Hg v 155/81 mm Hg; 44% v 12%). The age standardised mortality ratio in 1981-6 was lower than in a neighbouring village without a developed case finding programme (actual to expected deaths less than 65 = 21 to 22 in Glyncorrwg, 48 to 30 in control village). CONCLUSIONS: Whole population care through organised case finding and audit is feasible but only with a labour intensive approach combining accessibility, flexibility, and continuity, as well as a planned and structured approach, which requires substantial expansion of staff numbers and assiduous recording. It may reduce risks for at least some high risk groups. Despite their shortcomings the available data are consistent with the hypothesis that whole population care helps reduce mortality. Incentives in the new contract, which encourage the uncritical development of structured process, may diminish health outputs.

Adult

Multicenter controlled trial comparing high-frequency jet ventilation and conventional mechanical ventilation in newborn infants with pulmonary interstitial emphysema.

One hundred forty-four newborn infants with pulmonary interstitial emphysema were stratified by weight and severity of illness, and randomly assigned to receive treatment with high-frequency jet ventilation (HFJV) or rapid-rate conventional mechanical ventilation (CV) with short inspiratory time. If criteria for treatment failure were met, crossover to the alternate ventilatory mode was permitted. Overall, 45 (61%) of 74 infants met treatment success criteria with HFJV compared with 26 (37%) of 70 treated with CV (p less than 0.01). Eighty-four percent of patients who crossed over from CV to HFJV initially responded to the new treatment, and 45% ultimately met success criteria on HFJV. In contrast, only 9% of those who crossed over from HFJV to CV responded well to CV (p less than 0.01), and the same 9% ultimately met success criteria (p less than 0.05). Therapy with HFJV resulted in improved ventilation at lower peak and mean airway pressures, as well as more rapid radiographic improvement of pulmonary interstitial emphysema, in comparison with rapid-rate CV. Survival by original assignment was identical. When survival resulting from rescue by the alternate therapy in crossover patients was excluded, the survival rate was 64.9% for HFJV, compared with 47.1% for CV (p less than 0.05). The incidence of chronic lung disease, intraventricular hemorrhage, patent ductus arteriosus, airway obstruction, and new air leak was similar in both groups. We conclude that HFJV, as used in this study, is safe and is more effective than rapid-rate CV in the treatment of newborn infants with pulmonary interstitial emphysema.

Bronchopulmonary Dysplasia

Modulation of B cell maturation and migration to the thymus of SJL mice. B cell migration to the thymus.

The direct linkage of the B cell maturation process and infiltration of the thymus with mature B cells was studied in SJL mice. Phenotypically and functionally, B cells in the thymus of old SJL mice are mature B cells; IgM+, IgD+, Ly-1-, and evince a high proliferative response to lipopolysaccharide and a low one to dextran sulphate. Memory B cells can be found in the thymus of mice immunized with T-dependent or T-independent antigens. Chronic depletion and B cell maturation arrest induced by fractionated total lymphoid irradiation or by neonatal splenectomy eliminate B cells from the thymus and block their migration from the periphery to the thymus. When examined in adoptive transfer experiments, thymus B cells were found to possess a normal migration pattern and homing receptors; their migration pattern did not differ from that of lymph node or splenic B cells. It is evident, therefore, that the large number of normal functioning B cells in the thymus of SJL mice reflects a massive infiltration of the thymus by mature B cells from the periphery due to thymus dysfunction rather than to an abnormal in situ differentiation of intrathymic B cell precursors.

Animals

Structure-function analysis of human IL-6. Epitope mapping of neutralizing monoclonal antibodies with amino- and carboxyl-terminal deletion mutants.

To study the active site(s) of IL-6 we combined mutagenesis of IL-6 with epitope mapping of IL-6 specific mAb. In addition to amino-terminal deletion mutants we described previously, carboxyl-terminal deletion mutants were prepared. Functional analysis showed that deletion of only five carboxyl-terminal amino acids already reduced the bioactivity 1000-fold. A panel of mAb to IL-6 was subsequently analyzed by antibody competition experiments and binding to the amino- and carboxyl-terminal deletion mutants. On the basis of the competition experiments the six neutralizing mAb were divided in two groups (I and II). The binding pattern with the deletion mutants suggested that the region recognized by the four mAb in group I is composed of residues of amino- and carboxyl-terminus: binding of two mAb was abolished after deletion of amino acid Ala I-Ile26, of the third mAb after deletion of the four carboxyl-terminal amino acids whereas the fourth mAb did not bind to either mutant. Group II mAb retained binding to these mutants. Taken together these data suggest that in the native IL-6 molecule amino acid residues of amino and carboxyl terminus are in close proximity and that together they constitute an active site. Furthermore our data suggest that the part of the molecule recognized by group II antibodies is a second site involved in biologic activity.

Amino Acid Sequence

Pathology of skeletal muscle in mixed connective tissue disease.

To characterize the pathology of muscle involvement in mixed connective tissue disease (MCTD), skeletal muscle biopsies from 13 patients with MCTD were examined by routine light microscopy, histochemistry, and direct immunofluorescence. The histologic and histochemical changes observed corresponded closely to changes seen in idiopathic polymyositis and the myopathy associated with systemic lupus erythematosus. Eight of 13 cases examined by direct immunofluorescence demonstrated immunoglobulin deposition either within normal appearing vessels, within normal fibers, around or on the sarcoplasmic membrane, or within the perimysial connective tissue. The histologic findings support Sharp's observation of the high incidence of focal inflammatory lesions in skeletal muscle biopsies of patients with MCTD. Immunoglobulin deposition in these muscle biopsies suggests an immunologic basis for the muscular symptomatology in MCTD.

Basement Membrane

Inhibition of renal PGE2-9-ketoreductase by diuretics.

The metabolism of PGE2 by extracts of renal cortex is species dependent. In the rat PGE2-15-hydroxydehydrogenase initiates metabolism whereas in the rabbit PGE2-9-ketoreductase predominates. In man both mechanisms may operate. Each of the metabolic enzymes, which limits the vasodilator-diuretic actions of PGE2, was inhibited by ethacrynic acid, furosemide and indomethacin. Some inhibition of PGE2-9-ketoreductase was also observed with chlorthalidone, hydralazine and phentolamine but the thiazide diuretics and a number of other cardiovascular-active agents were without significant effect. We conclude that the inhibition of PGE2-9-ketoreductase and PGE2-15-hydroxydehydrogeanse could contribute to the mechanism of action of the non-thiaxide diuretics in man.

Alcohol Oxidoreductases

Competency-based education.

The essential elements of a P/CBDE program include the delineation of role-derived dietetic competencies, which are publicly stated in behavioral terms. The criteria used to measure the accomplishment of these competencies are criterion-referenced, and the student acquires the competencies at his own rate. Much confusion exists in differentiating between the essential characteristics and implementation modes. The use of modern technology and modular packaging of learning experiences does not automatically lead to a P/CBDE program. These are merely tools. The clear identification of competencies, objectives, and performance criteria are the essence of P/CBDE. Currently, dietetic educators are formulating competencies for their own programs. A national group of "experts" will need to be convened to develop competencies for the profession as a whole.

Clinical Competence

Prostaglandin-E2-9-ketoreductase in rabbit kidney.

The 100,000 xg supernatant of rabbit kidney contains a prostaglandin-E2-9-ketoreductase which has an obligatory requirement for NADPH. This enzyme is localised in the renal cortex and is able to quantitatively convert PGE2 to PGF2alpha. A broad pH profile was evident with an optimum at pH 7 with 5. Kinetic studies indicated a Km of 3 with 2 x 10-4M PGE2. The isoelectric point was at pH 5 with 65 and the molecular weight, as estimated by gel filtration, was 21,800. These values differ from those obtained with enzyme from monkey brain tissue and suggest a tissue specificity of PGE2-9-ketoreductase. By combining isoelectric focussing techniques with sephadex filtration considerable purification of the renal enzyme was achieved.

Alcohol Oxidoreductases

The dietitian and credentialing.

The meaning and ramifications of credentialing and accreditation have direct and powerful implications for the professional dietitian. There is also intense interest on the part of the public, as it views each profession's role in providing health care, as to the quality and expense ot that care. Each dietitian's analysis of the direction our Association must take in accreditation and credentialing is mandatory to the growth of nutritional care and its responsiveness to the needs of the American people. Issues have been presented and reviewed in this article. Some proposals for change have been suggested. By no means is the issue of accreditation or credentialing static among the health professions. New studies are being started routinely. New ideas and issues are continually being proposed and analyzed. What is good today for the practitioner and the public may be non-functional tomorrow. However, it seems certain that changes are imminent. It is imperative that each member of The American Dietetic Association assume an active role in the decisions that will be made for the future of each of us.

Accreditation