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Biomedical subjects

M Weinberg

Publications and source records attributed to M Weinberg.

At least 19 recordsLinked to original sources
PubMed1992

Sequencing of the variant thyroxine-binding globulin (TBG)-San Diego reveals two nucleotide substitutions.

Thyroxine-binding globulin (TBG) is a liver glycoprotein that transports thyroid hormone in serum. In 1989, a variant TBG was reported with reduced binding affinity for thyroxine (T4) and triiodothyronine (T3) which results in low serum T4 and T3 levels. This variant, TBG-San Diego (TBG-SD), also displays reduced heat stability but has a normal isoelectric focusing pattern. We now report the sequence of the entire coding region of TBG-San Diego. It reveals two nucleotide substitutions: one located in exon 1 which results in the replacement of the normal Ser-23 (TCA) with threonine (ACA) and the other, located in exon 3, changes the normal codon 283 of TTG (leucine) with that of TTT, (phenylalanine). Allele specific amplification was used to search for both nucleotide substitutions in four affected members of the family. Results confirmed the co-segregation of these nucleotide substitutions with the TBG-SD phenotype. The substitution in codon 283 has been previously described and exists as a polymorphism in some ethnic groups or in combination with other TBG variants with different physical characteristics. Thus, it appears that the replacement of Ser-23 with threonine is responsible for the observed alterations in physical properties of TBG-San Diego.

Amino Acid Sequence↗
PubMed1992

Cardiodepressant effects of mexiletine in patients with severe left ventricular dysfunction.

Mexiletine is thought to exert minimal negative inotropic actions, but its effects have not been evaluated in patients with severe congestive heart failure. The haemodynamic response to an oral loading dose of mexiletine (400 mg) was assessed in 20 patients with severe chronic heart failure. Mexiletine caused marked haemodynamic deterioration, with stroke work index decreasing in 18 of the patients. Two hours after mexiletine, mean cardiac and stroke work indexes decreased by 15% and 25%, respectively (both P less than 0.001), while heart rate and systemic vascular resistance increased by 10% and 20%, respectively (both P less than 0.05). Simultaneously, left ventricular filling pressure and right atrial pressure increased by 37% and 36%, respectively (both P less than 0.001), but mean arterial pressure did not change. Furthermore, clinical deterioration, with onset of dyspnoea at rest, developed in five patients at the time of peak haemodynamic effect. Plasma mexiletine concentrations were within the accepted therapeutic range of 0.5 to 2.0 micrograms.ml-1 in all but two of the patients. Nevertheless, the plasma concentration was an important determinant of haemodynamic effect. The stroke work index decreased by 38% in the patients with a mexiletine level above the median value of 1.3 micrograms.ml-1 (range 25 to 56%), but only 13% (range 15 to 43) in patients with lower plasma concentrations. In conclusion, although mexiletine may cause cardiodepressant effects in any patient with severe left ventricular dysfunction, dosing which results in a high (but still therapeutic) plasma level is more likely to cause haemodynamic deterioration.

Adult↗
PubMed1992

Elevated concentrations of endogenous ouabain in patients with congestive heart failure.

BACKGROUND: An endogenous digitalis-like compound in mammals has long been postulated, but only recently has a substance indistinguishable from ouabain been identified in human plasma. Because of the potential significance of such a substance in patients with congestive heart failure, we sought to evaluate the pathophysiology of endogenous ouabain in these individuals. METHODS AND RESULTS: Using an immunoassay, we determined plasma ouabain concentrations in 51 patients with heart failure and in 19 control subjects. Plasma ouabain concentrations in control subjects ranged from 0.16 to 0.77 nM (mean, 0.44 +/- 0.20 nM). In 19 matched heart failure patients receiving digoxin, the mean ouabain was significantly elevated at 1.59 +/- 2.2 nM (range, 0.17-8.76 nM, p less than 0.05 versus control subjects). The ouabain concentration correlated inversely with both cardiac index (r = -0.62, p less than 0.005) and mean arterial pressure (r = -0.51, p less than 0.05). However, there was no correlation between ouabain and left ventricular filling (r = 0.19, NS) or right atrial pressures (r = 0.20, NS). In 16 heart failure patients not receiving digoxin, the mean ouabain was 1.52 +/- 2.58 nM. No relation between renal function and ouabain was detected. CONCLUSIONS: The unanticipated lack of correlation of ouabain with atrial pressures indicates that volume is not the chief determinant of ouabain concentration in patients with congestive heart failure. However, the significant relations of plasma ouabain concentration with cardiac index and mean arterial pressure imply that endogenous ouabain may be an important homeostatic factor in humans.

Digoxin↗
PubMed1991

Hemodynamic and neurohormonal effects of quinidine in patients with severe left ventricular dysfunction secondary to coronary artery disease or idiopathic dilated cardiomyopathy.

Quinidine causes vasodilation directly and by inhibition of adrenergic vasoconstriction, but it also exerts negative inotropic activity. Although this drug is often administered to patients with severe congestive heart failure, the net consequences of these opposing actions have not been evaluated in such patients. The hemodynamic and neurohormonal response to oral quinidine (600 mg) in 19 patients with severe chronic heart failure was therefore determined. Vasodilation was the predominant effect of quinidine, with reductions in mean arterial, left ventricular filling and right atrial pressures of -9% (confidence interval [CI] -5 to -13), -8% (CI -19 to 3), -15% (CI -26 to -4), respectively. The quinidine-induced vasodilation increased plasma norepinephrine and epinephrine concentrations by 44% (CI +17 to +72) and 47% (CI +2 to +91), respectively. No change in cardiac performance was noted, with the cardiac index slightly increased (+10%, CI +2 to +17) and stroke work index unchanged (0%, CI -11 to +11) after quinidine. Although the mean serum quinidine concentration was within the therapeutic range or lower in all patients, the serum quinidine concentration and the change in mean arterial pressure did correlate (r2 = 0.64). In conclusion, vasodilation is the predominant hemodynamic effect of oral quinidine in patients with congestive heart failure. However, potential adverse effects may be caused by consequent neurohormonal activation.

Adult↗
PubMed1991

Comparative hemodynamic effects of mexiletine and quinidine in patients with severe left ventricular dysfunction.

Mexiletine and quinidine are often administered to patients with severe congestive heart failure, but their hemodynamic effects have not been adequately studied in these individuals. In a randomized, crossover study, the hemodynamic responses to single oral doses of quinidine (600 mg) and mexiletine (400 mg) were compared in 20 patients with marked left ventricular dysfunction. Quinidine predominantly caused vasodilation, with mean arterial, left ventricular filling, and right atrial pressures all decreasing (-7 +/- 2, -2.3 +/- 1.0, and -1.1 +/- 0.5 mm Hg, respectively) and the systemic vascular resistance also declining (-308 +/- 84 dynes.sec.cm5). In contrast, the systemic vascular resistance increased (314 +/- 84 dynes.sec.cm-5) and the mean arterial, left ventricular filling, and right atrial pressures also increased (+2 +/- 2, +6.1 +/- 1.8, and +1.8 +/- 0.6 mm Hg, respectively) after mexiletine. Cardiac performance declined with mexiletine (cardiac and stroke work indexes decreasing -0.3 +/- 0.1 L/min/m2 and -5 +/- 1 gm.m/m2, respectively), but there was no significant change in cardiac or stroke work indexes with quinidine (+0.1 L/min/m2 and -0.3 +/- 0.9 gm.m/m2, respectively). The response to the two agents significantly differed for all parameters measured (p less than 0.005). These hemodynamic changes were accompanied by clinical effects. Mexiletine induced increased dyspnea in five patients and quinidine led to symptomatic hypotension in two patients. Plasma concentrations of mexiletine and serum concentrations of quinidine were within or below the therapeutic range in all patients. In conclusion, mexiletine and quinidine exert different hemodynamic effects when given to patients with severe congestive heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Immunoglobulins A, G, and M to cytomegalovirus during recurrent infection in recipients of allogeneic bone marrow transplantation.

Occurrence and significance of specific IgA and IgM to cytomegalovirus (CMV) in recurrent CMV infection was evaluated in 21 allogeneic T lymphocyte-depleted bone marrow transplantation (BMT) recipients who had been previously CMV seropositive. Of 17 patients with CMV infection, viruria was detected in 94%, CMV-specific IgA in 88% and IgM in 76%, and a fourfold rise in IgG in 65%. The median time between BMT and detection of viruria was 69 days, of IgA 70, of IgM 62, and of IgG 88 days. The IgM and IgA responses lasted for 14 and 30 days (median time), whereas high IgG titers persisted. Twelve patients developed CMV disease; in these the appearance of viruria, IgA, and IgM preceded the rise of IgG (P less than .02). CMV-specific IgA and IgM are valuable diagnostic tools in BMT recipients with recurrent CMV infection.

Adolescent↗
PubMed1991

Prevalence of sexually transmitted pathogens among women attending a methadone clinic in Israel.

OBJECTIVE: To assess the prevalence of sexually transmitted pathogens in drug-addicted women in Tel Aviv, Israel. DESIGN: A prospective study conducted between March and July 1987. SETTING: A methadone clinic in Tel Aviv, Israel. SUBJECTS: Sixty four asymptomatic female drug addicts were studied; 38 of them were declared practising prostitutes. METHODS: Cervical specimens were obtained for cultures, and blood samples were drawn for serological tests. Demographic data and sexual histories were obtained using a standard questionnaire. RESULTS: Chlamydia trachomatis was detected in the cervix of 25% of women; 98% had antibody titres (greater than 1:64). Mycoplasma hominis and Ureaplasma urealyticum were isolated in 57% and 65% respectively. Gardnerella vaginalis was detected in 17% of women, and herpes simplex virus was cultured from two prostitutes. Five per cent of women were carriers of HBsAg, while 57% had HBSs and/or HBc antibodies. Only one prostitute had specific treponemal antibodies. In no case were gonococci or group B streptococci isolated, and HIV serology was invariably negative. CONCLUSION: Chlamydia and genital mycoplasmas appear to be the prevailing pathogens in Israeli drug-addicted women, while gonococci and Treponema pallidum occur only rarely.

Adult↗
PubMed1990

Cytogenetic investigations on a cell line derived from a carcinoma arising in a salivary gland pleomorphic adenoma.

This article discusses the results of cytogenetic investigations of a cell line derived from a malignant tumor arising in a benign salivary gland pleomorphic adenoma. Initial karyotypic studies became possible with cells of the second in vitro passage and revealed the existence of hypertetraploidy. Furthermore, a marked polysomy 7 and a translocation involving 12q13-15, a breakpoint also frequently seen in benign pleomorphic adenomas, were noteworthy. During long term culture, the number of chromosomes per cell decreased as well as the number of copies of chromosome 7. Cell tumorigenicity was proved by heterotransplantation to nude mice. The resulting tumors were karyotyped again. No significant changes of the chromosome number or of the degree of polysomy 7 were found compared to the cells before heterotransplantation. In contrast, the cells from the nude mice tumors showed a remarkable number of different isochromosomes probably indicating an unknown factor supporting the generation of isochromosomes. The consistent presence of the t(12;?)(q13-15;?) makes the cell line well suited for molecular studies of this breakpoint region.

Adenoma, Pleomorphic↗
PubMed1989

Limitations to the use of a sensitive assay for serum thyrotropin in the assessment of thyroid status.

In the majority of clinical settings, a suppressed serum thyrotropin (s-TSH) level determined by the new sensitive assays is diagnostic of thyrotoxicosis. This has led to its proposed use as a screen for thyroid disease. However, s-TSH may be suppressed in conditions other than thyrotoxicosis. We retrospectively reviewed s-TSH measurements made in a large heterogeneous population to determine in which settings a suppressed value could potentially lead to misdiagnosis. We found that a suppressed s-TSH level was useful in making the diagnosis of autonomous thyroid function and in the assessment of thyroid hormone replacement therapy in patients with primary, but not central, hypothyroidism. Hyperthyroidism caused by either intrinsic thyroid disease or thyroid hormone administration accounted for 83% (111/134) of suppressed values; however, central hypothyroidism, nonthyroidal illness, acute psychiatric illness, or the administration of medication was responsible for this finding in 17% (23/134). While a suppressed s-TSH level is generally excellent in the diagnosis of pituitary suppression by thyroid hormone, in specific clinical settings, a suppressed s-TSH level may be seen in the absence of thyroid hormone excess. The limitations of its use as a first-line screen in those conditions must be recognized.

Adult↗
PubMed1988

Ceftizoxime vs. cefotaxime--a comparative randomized multicenter study.

One hundred and fourteen hospitalized patients with moderate or severe infections were assigned at random, in four medical centers, to receive either ceftizoxime or cefotaxime, administered intravenously in a dosage of 1 to 2 g every 8 h. Of 96 patients evaluable for efficacy, 24 (25%) had bacteremia, 46 (48%) had urinary tract infections and 9 (9%) had pneumonias. Half the patients had been treated ineffectively by other antibiotics prior to the study drug treatment. The overall clinical efficacy was 90% in both treatment groups and 83% in both groups with bacteremia. All patients with urinary tract infection were cured by both agents. Bacteriological eradication rate was 95% in both groups. Adverse reactions, though mild, were more frequent in the cefotaxime group (13.5%) than in the ceftizoxime group (6.8%); superinfection rate was higher in the ceftizoxime group. Both antibiotics were highly and equally efficacious in the therapy of severe infections in hospitalized patients.

Adult↗
PubMed1986

Isoelectric focusing variant thyroxine-binding globulin in American blacks: increased heat lability and reduced serum concentration.

Three major bands of T4-binding globulin (TBG) at pH 4.3-4.5 are seen after isoelectric focusing (IEF) of serum. Daiger et al. detected a cathodal shift of all IEF bands in some American blacks, and found that the inheritance of this variant TBG (TBG-S) is X-chromosome linked. However, the properties of the TBG-S molecule and its possible association with changes in thyroid function have not been studied. Based on IEF analysis of 114 serum samples from adult American blacks, the gene frequency of TBG-S was 12.0%, and the genotype distribution was consistent with X-chromosomal linkage. TBG-S and the common type TBG (TBG-C) co-occurred exclusively in sera from women, whereas sera from men had only TBG-C or TBG-S, confirming the X-linked inheritance of this variant TBG. At 60 C, TBG-S was denatured with a mean t1/2 of 4.7 +/- 0.9 (+/-SD) min compared to 6.8 +/- 1.1 min for TBG-C (P less than 0.001). Heterozygous females with TBG-CS had an intermediate rate of heat denaturation (t1/2, 5.2 +/- 0.7 min). In vitro mixtures of TBG-S and TBG-C also had intermediate t1/2 values, indicating that the heat lability of TBG-S is inherent to the variant TBG molecule. Heat denaturation resulted in loss of T4-binding activity, which was proportional among corresponding IEF bands for each of the two TBG types. Larger amounts of added T4 were required to protect against the heat-induced denaturation of TBG-S. No changes in the affinity of TBG-S for T4 could be demonstrated by analysis of binding kinetics at O C. Thyroid function tests were carried out in 10 black men with TBG-S and 10 age-matched black men with TBG-C. The mean concentration of total T4 (TT4) of 6.8 +/- 1.5 micrograms/dl in the group of TBG-S men was lower (P less than 0.02) than that in the group of TBG-C men (8.5 +/- 1.3 micrograms/dl). The finding of lower levels of TT4 in men with TBG-S was best explained on the basis of a concomitant reduction of serum TBG concentration (1.41 +/- 0.30 vs. 1.72 +/- 0.23 mg/dl; P less than 0.05). This conclusion was confirmed when no significant difference in mean TT4 concentration was found between the group with TBG-S and another with TBG-C matched by serum TBG concentration.(ABSTRACT TRUNCATED AT 400 WORDS)

Autoradiography↗
PubMed1979

Interrupted aortic arch operation in the first week of life: hemodynamic and angiographic evaluation one year later.

Operation for interrupted aortic arch (IAA) was successful in 2 infants during the first week of life. Both had postoperative hemodynamic and angiographic evaluation at one year of age. The first infant had a type A IAA, and prostaglandins were infused to prevent ductal closure prior to the insertion of a graft between the two ends of the interrupted aorta. The second infant had a palliative operation for type B IAA (pulmonary artery banding and graft from main pulmonary artery to descending aorta). These patients represent the ninth and tenth successful operations for IAA in this age group and are reported with long-term reevaluation.

Age Factors↗
PubMed1979

Prevention of air embolism after mitral valve replacement with a porcine heterograft prosthesis.

The production of prosthetic valve incompetence during atriotomy closure is among the operative maneuvers utilized to prevent air embolism in mitral valve replacement. The leaflets of a porcine bioprosthesis may be retracted safely and effectively, thereby producing temporary valve incompetence, by placing three polypropylene sutures through the valve orifice and around the sewing ring to encircle the leaflets. These traction sutures are eaily pulled out through the atriotomy suture line after all air has been displaced from the heart. The technique has been effective, easily accomplished, and without complications.

Animals↗