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Biomedical subjects

M Hart

Publications and source records attributed to M Hart.

At least 19 recordsLinked to original sources
PubMed1992

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

A comparison of Collins and UW solutions for cold ischemic preservation of the rat liver.

A new solution which can extend successful preservation times for hepatic allografts was recently developed at the University of Wisconsin (UW). To examine the mechanism of improved viability using this solution, we developed a model of orthotopic hepatic transplantation in the rat. As a baseline study, we compared parameters of viability of allografts preserved in Collins solution to those preserved in UW, including survival, bile output, peak AST, and allograft weight change during storage. Seventy-four rats were transplanted following storage in Collins solution and 70 rats were transplanted after storage in UW. Cold-storage time varied between 2 and 24 hr. The survival with preservation in UW was significantly better than that with Collins when storage time was greater than 2 hr. The preservation time for a viable organ using UW was greater than double that using Collins. The peak AST using UW was lower than that with Collins for cold ischemic times (CIT) up to 10 hr, with significance demonstrated at 5-6 and 7-8 hr when compared with Collins. Prolonged CIT resulted in an increase in liver weight with Collins-preserved livers and a decrease in weight with UW-preserved livers. Using a model of orthotopic liver transplantation in the rat, we demonstrated a doubling of preservation time when UW solution was substituted for Collins. Similar improvements in recipient survival and biochemical parameters of injury have been demonstrated in the canine model and in human clinical trials.

Adenosine↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

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↗
PubMed1989

Analysis of human IL-6 mutants expressed in Escherichia coli. Biologic activities are not affected by deletion of amino acids 1-28.

We have constructed and analyzed amino terminally deleted analogs of IL-6. Progressively shortened variants of mature IL-6 were constructed at the cDNA level and expressed in Escherichia coli. Mutant proteins were recovered from refractile bodies by solubilizing in 6 M guanidine-HCl. The mutant protein concentration in these preparations was estimated by Western blotting by using an IL-6-specific mAb and the biologic activity was measured in the B9 (hybridoma growth factor) assay. The first 28 amino acids of mature IL-6 could be removed without significantly affecting biologic activity. A further removal of amino acids 29 and 30 resulted in an approximately 50-fold decrease, whereas removal of amino acids 31 to 34 virtually abolished the activity. The mutants showed the same reaction pattern in three other IL-6 assays: induction of murine thymocyte proliferation, induction of fibrinogen synthesis by a human hepatoma cell line (HepG2), and the induction of IgM synthesis by an EBV-transformed B cell line. This suggests that a single functional domain might be responsible for all four activities of IL-6.

Amino Acid Sequence↗
PubMed1989

Blood and graft eosinophilia as predictors of rejection in human liver transplantation.

This study attempts to define the relationship of blood and graft eosinophilia to acute hepatic allograft rejection. Sixty liver transplant patients were studied for the first 30 days postoperatively, with daily serum bilirubin and liver enzyme levels, white blood cell counts and differential counts, and biweekly core liver biopsies. Graft eosinophilia was established if 7% or greater of the cells infiltrating the portal triads were eosinophils. Blood eosinophilia is an absolute eosinophil count greater than 500 cells/mm3 occurring on any of the 5 days preceding the day of rejection. Acute rejection was diagnosed when 2 days of hepatic allograft dysfunction occurred with histologic evidence of rejection. The 2nd day of dysfunction with appropriate histologic findings was arbitrarily chosen as the day of rejection. Graft eosinophilia predicted rejection with 92% sensitivity and 98% specificity. Blood eosinophilia occurred on the average on the day of rejection and on the 2 preceding days, while graft eosinophilia occurred on the day of rejection and on 1 preceding day. Blood eosinophilia followed by graft eosinophilia specifically occurred in cases of rejection. Blood eosinophilia not followed by graft eosinophilia was not associated with rejection. Following treatment of rejection with high-dose corticosteroids, blood and graft eosinophil counts decreased markedly. In summary: (1) graft eosinophilia is very sensitive and specific for acute hepatic allograft rejection; (2) blood eosinophilia closely precedes and parallels graft eosinophilia specifically during acute hepatic allograft rejection; and (3) elevated blood and graft eosinophil counts are markedly reduced following treatment of rejection with high-dose corticosteroids.

Eosinophilia↗
PubMed1989

An analysis of the determinants of hepatic allograft rejection using stepwise logistic regression.

Hepatic allograft rejection is currently diagnosed using both histologic and clinical criteria. The purpose of this study is to extract data from the allograft biopsy, which can establish the diagnosis of rejection with more precision. A total of 566 allograft biopsies were examined in 56 patients following orthotopic liver transplantation, and 35 variables were examined. Using stepwise logistic regression, only six of these variables affected the diagnosis of rejection. These were portal tract spillover, portal tract eosinophilia, portal vein endothelialitis, portal tract neutrophilia, central vein endothelialitis, and cholestasis. Coefficients of these variables were determined, and could be used to calculate the probability of rejection for a given biopsy. Using this model the probability of having rejection can be calculated using histologic data alone.

Biopsy↗
PubMed1988

Proteolytic cleavage of the precursor of von Willebrand factor is not essential for multimer formation.

Monkey kidney cells (COS-1), transfected with full-length human von Willebrand factor (vWF) cDNA encoding the precursor of vWF (pro-vWF), mimic the characteristics of the biosynthesis and of the constitutive secretory pathway, displayed by cultured vascular endothelial cells. Such heterologous transfected cells are able to cleave pro-vWF, generating the propolypeptide and mature vWF, and to assemble pro-vWF dimers into a series of multimers, similarly to endothelial cells. Evidence is presented showing that proteolytic processing of pro-vWF by COS-1 cells occurs at the peptide bond between arginine and serine in the sequence Lys762-Arg763-Ser764, identical to endothelial cell-associated proteolysis. This conclusion stems from the observation that substitution of Arg763 by a glycine residue completely abolishes proteolytic processing. As a result, transfection of COS-1 with the mutant vWF-Gly763 cDNA does not significantly affect the multimeric organization of secreted vWF molecules. Consequently, we conclude that proteolytic processing of pro-vWF is not required for multimer formation. Pulse-chase labeling of COS-1 cells transfected with full-length vWF cDNA reveals pro-vWF exclusively in cell lysates, whereas both pro-vWF and mature vWF are encountered in the conditioned medium. These observations indicate that proteolytic processing of pro-vWF is a "late" event during intracellular routing of these molecules or may occur extracellularly.

Animals↗
PubMed1988

Idiopathic dilated cardiomyopathy. Role of programmed electrical stimulation and Holter monitoring in predicting those at risk of sudden death.

The prognostic role of programmed electrical stimulation and Holter monitoring was evaluated in 21 patients with idiopathic dilated cardiomyopathy who had no prior history of ventricular tachyarrhythmias. During a mean follow-up period of 23 months, sudden death or ventricular fibrillation occurred in four (20 percent). One patient died of complications of sepsis, and one underwent cardiac transplantation. Programmed electrical stimulation (PES) resulted in five or more beats of induced ventricular tachycardia in seven patients (33 percent), but was a poor predictor of sudden death (sensitivity = 20 percent). Thirteen patients (62 percent) had complex ventricular ectopy (Lown class 4A or 4B) by ambulatory monitoring. This was a sensitive (80 percent) but not specific (31 percent) marker for sudden death. The predictive value of a negative Holter monitor study was high (80 percent) for identifying those at low risk of sudden death. The results of this prospective study suggest that programmed ventricular stimulation and routine ambulatory monitoring are poor predictors of sudden death in this population.

Adult↗
PubMed1987

Multiple congenital anomalies syndrome with myopathy in chromosome 16 abnormality.

An abnormality of chromosome 16 in an eight year-old male was associated with a multiple congenital anomalies syndrome characterized by myopathy, cataracts, blepharophimosis, microcephaly, failure to grow, profound mental retardation, moderate sensorineural hearing loss, grand mal seizures, bilateral inguinal hernia, and thoracolumbar kyphoscoliosis. Magnetic resonance imaging of the head demonstrated absence of the corpus callosum and extensive loss of brain parenchyma in the occipital regions. Chromosome analysis from peripheral blood of the patient showed a recombinant chromosome 16 [46, XY, rec (16), dup (p13.1----p13.3) del (q22----q24)]. The mother had a pericentric inversion of chromosome 16 [46, XX, inv(16) (p13.1;q22)]. Independent recombinant DNA studies have shown that the breakpoints of these chromosomal rearrangements flank the alpha-globin gene cluster locus.

Abnormalities, Multiple↗
PubMed1987

Expression of variant von Willebrand factor (vWF) cDNA in heterologous cells: requirement of the pro-polypeptide in vWF multimer formation.

Von Willebrand factor (vWF) is a multimeric plasma glycoprotein synthesized by vascular endothelial cells as a pre-pro-polypeptide with a highly repetitive domain structure, symbolized by the formula: (H)-D1-D2-D'-D3-A1-A2-A3-D4-B1-B2-B3-C1-C2-(OH) A heterologous expression system for the synthesis of recombinant vWF protein was developed, consisting of a monkey kidney cell line (COS-1), transfected with full-length vWF cDNA. This system was shown to mimic the constitutive secretory pathway of vWF in endothelial cells, since dimerization and multimerization occur similarly. To determine whether the pro-polypeptide, composed of the domains D1 and D2, is involved in vWF multimerization, a vWF cDNA was constructed that lacked the coding sequence for the pro-polypeptide. The mutant vWF protein, expressed by COS-1 cells transfected with this cDNA, did not assemble beyond the dimer stage. From this observation, we conclude that (i) dimerization does not involve the pro-polypeptide of pro-vWF and (ii) the presence of the pro-polypeptide, as part of pro-vWF, is obligatory for multimerization. It is argued that the interactions, required for interchain binding, are mediated by the D domains.

Animals↗