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Biomedical subjects

B M Friedman

Publications and source records attributed to B M Friedman.

16 recordsLinked to original sources
PubMed1995

Postinfarction ventricular aneurysms.

Ventricular aneurysms are circumscribed, thin-walled fibrous, noncontractile outpouchings of the ventricle. The majority are apically located, true aneurysms of the left ventricle (LV) that occur as a consequence of transmural myocardial infarction (MI). The precursor of aneurysm formation appears to be infarct expansion early after acute MI and occurrence generally relates to infarct size. The presence of underlying hypertension and the use of steroids and nonsteroidal antiinflammatory agents may promote aneurysm formation. The clinical sequelae include congestive heart failure (CHF), thromboembolism, angina pectoris, and ventricular tachyarrhythmias. Late rupture is a particular complication of false aneurysms in which the pericardium is the aneurysm wall. The diagnosis may be suspected by the clinical finding of a diffuse, pansystolic apical thrust, persistent ST-segment elevation on the electrocardiogram, and distortion of the cardiac silhouette on chest x-ray. This can be confirmed using echocardiography, radionuclide ventriculography, and cardiac catheterization. The latter has the additional advantage of being able to delineate the coronary anatomy. Management involves prevention, specific therapy for the various clinical manifestations, and surgery. Therapeutic interventions with thrombolytic agents, aspirin, heparin, and beta blockers that are applied early in the evolution of an MI may limit infarction size, thereby reducing the tendency toward infarct expansion and aneurysm formation. Patients with mild CHF can usually be controlled with the standard combination of angiotensin-converting enzyme inhibitors, diuretics, and digoxin. Thromboembolism is best prevented by anticoagulation with warfarin for at least 3 months after the acute MI. The choice of pharmacotherapy for ventricular tachyarrhythmias should be guided by electrophysiologic studies. The treatment of patients with angina pectoris utilizes conventional therapeutic modalities.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart Aneurysm↗
PubMed1995

Early interventions in the management of acute uncomplicated myocardial infarction.

The demonstration that the vast majority of acute transmural myocardial infarctions are caused by an occlusive thrombus in the coronary artery, together with the concept that myocardium can be salvaged for a period of time after the onset of such occlusion, has heralded a new era of management of this disorder. This involves an aggressive interventional approach aimed at restoring coronary artery patency early while decreasing myocardial oxygen demands. Abundant data show that coronary flow can be reestablished using either intravenous chemical thrombolytic agents (tissue-type plasminogen activator and streptokinase), percutaneous transluminal coronary angioplasty, or coronary artery bypass grafting. Conjunctive aspirin or heparin therapy (or both) is effective in maintaining vessel patency once perfusion is restored. Myocardial oxygen demand can be reduced, where feasible, by pharmacotherapy and control of the patient's associated pain and anxiety. The beta-adrenergic blockers and nitrates are particularly suitable in this regard, and angiotensin-converting enzyme inhibitors favorably affect infarct expansion and ventricular remodeling. With such an approach, infarct size can be reduced, leading to improved left ventricular function--the prime determinant of morbidity and mortality in patients with acute infarction. The in-hospital mortality has fallen from about 30% three decades ago to less than 8% in many coronary care units.

Adrenergic beta-Antagonists↗
PubMed1994

Serum transferrin receptor in hereditary hemochromatosis and African siderosis.

The present investigation evaluated the serum transferrin receptor concentration in subjects with nontransfusional iron overload who were identified in two separate studies on the basis of a serum ferritin level above 400 micrograms/L. Subjects with preclinical hereditary hemochromatosis were evaluated in the first study and those with the African form of iron overload in the second. In the first study, hereditary hemochromatosis was identified in 14 white men on the basis of a persistent elevation in transferrin saturation above 55%. The serum receptor concentration was elevated above the upper cut-off of 8.5 mg/L in two of the subjects, but the mean receptor of 6.1 +/- 1.4 mg/L (mean +/- 2 SE) did not differ significantly from the normal mean for this assay of 5.6 +/- 0.3 mg/L. In the same study, 60 control subjects with secondary iron overload were identified on the basis of a serum ferritin persistently above 400 micrograms/L, with a normal serum C-reactive protein concentration but with a transferrin saturation < 55%. Three of these subjects had an elevated serum receptor concentration but the mean value of 5.5 +/- 0.4 mg/L did not differ from normals nor from subjects with hemochromatosis. In the second study, 49 black Africans with iron overload were divided into those with or without an elevated transferrin saturation. The mean serum receptor concentration of 5.0 +/- 0.8 mg/L and 4.5 +/- 0.4 mg/L, respectively, did not differ statistically. It was concluded that there is no evidence of generalized dysregulation of the transferrin receptor in hemochromatosis or African siderosis.

Adult↗
PubMed1992

The importance of assessing time-course behaviour of abnormal ST/T changes after exercise.

Routine stress electrocardiography has been criticised for yielding too many so-called 'false-positive' results because ST/T changes that develop during and after exercise are prevalent. Recent studies in our institution indicate, however, that the time-course behaviour patterns of these ST/T configurational 'abnormalities' after exercise are different from those reflecting myocardial ischaemia due to epicardial coronary artery disease (CAD). Time-course analysis increases the predictive value of exercise testing and has dramatically decreased the number of asymptomatic subjects or symptomatic patients at low risk of having CAD being subjected to coronary arteriography in our institution. Our method of assessing post-exercise time course patterns of abnormal ST/T are described in detail. Ischaemic ST/T abnormalities have late onset, early offset or early onset, late offset whereas those ST/T changes associated with normal epicardial coronary arteries have late onset, late offset or early onset, early offset post-exercise time course patterns.

Coronary Disease↗
PubMed1991

Observer accuracy and confirmation of the important role of abnormal ST/T time course behavior in the evaluation of stress electrocardiograms.

Routine exercise electrocardiography has been criticized for yielding too many so-called "false-positive" results. Recent studies in our institution indicate that evaluation of the time course behavior of ST segment and T wave (ST/T) changes after cessation of exercise differentiates ischemic from non-ischemic ("false-positive") stress electrocardiograms (SEs). Our method of assessing time course behavior is clarified. The principal aim of this study was to determine the accuracy of experienced observers in making this differentiation. Records of consecutive patients undergoing coronary arteriography over a 2 year period were reviewed and 30 with SEs judged positive for ischemia by the widely accepted ST/T configurational criteria alone were selected at random for the investigation. Sixteen subjects had normal coronary angiograms and had therefore previously been regarded as having false-positive SEs. Fourteen patients had at least one significantly (> 70%) stenosed coronary artery which was our yardstick for ruling that true myocardial ischemia, due to epicardial coronary artery disease (CAD), was present. Five observers, familiar with post-exercise ST/T time course patterns, independently and "blindly" analyzed all 30 configurationally abnormal SEs. Observers were informed only of the patient's age and sex; they were thus unaware of symptoms, exercise variables, coronary anatomy and the number of patients in the 2 groups. The observer consensus for ischemia of SEs using time course analysis was: total test accuracy 87%, sensitivity 79%, specificity 94%, positive predictive value 92% and negative predictive value 83%. Because all 30 patients had ST/T abnormalities, results of the sample for ischemia based on configurational criteria alone were sensitivity 100%, specificity 0% and positive predictive value 47%. We concluded that time course analysis plays a crucial role in evaluating SEs and that exercise electrocardiography remains a safe, cost-effective and reliable method of screening many asymptomatic, as well as symptomatic, subjects for CAD.

Coronary Angiography↗
PubMed1991

Post-exercise time-course analysis of ST segment and T wave changes: an important contribution to the role of stress electrocardiography in aircrew.

Flight surgeons recognize that ongoing vigilance is necessary to detect coronary artery disease (CAD) in aircrew. Regular physical examinations with only a resting electrocardiogram, albeit having a very low predictive value for detection of CAD in asymptomatic subjects, are now widely practised. Routine stress electrocardiography has been criticized for yielding too many so-called "false positive" results because ST/T changes that develop during and after exercise are prevalent. Recent studies in our institution indicate, however, that the time-course behavior patterns of these ST/T configurational "abnormalities" after exercise are different from those reflecting myocardial ischemia due to epicardial CAD. Time-course analysis increases the predictive value of exercise testing and has dramatically decreased the number of asymptomatic aircrew being subjected to coronary arteriography in our institution. Routine exercise electrocardiography provides a reliable, cost-effective means of detecting aircrew with CAD and a baseline for comparison at subsequent examination, and we strongly recommend that it be universally reinstated.

Adult↗
PubMed1990

Dietary iron overload in southern African rural blacks.

A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and serological screening for hepatitis B and human immunodeficiency virus (HIV) infections were carried out in 370 subjects (214 inpatients and 156 ambulatory Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin concentration was much higher in the male hospital patients than in subjects living in the community [1,581 micrograms/l (421-5,944 micrograms/l) and 448 micrograms/l (103-1,945 micrograms/l) respectively] suggested that dietary iron overload was not the only factor raising the serum ferritin concentration. The major additional factor appeared to be inflammation, since the geometric mean (SD range) serum CRP was significantly higher in male hospital patients [21 mg/l (8-53 mg/l)] than in subjects in the community [3 mg/l (1-5 mg)]. Alcohol ingestion, as judged by history and by serum GGT concentrations, was also associated with significantly raised serum ferritin concentrations. This finding was ascribed to the fact that traditional brews are not only associated with alcohol-induced hepatic damage but are also a very rich source of highly bio-available iron. The role of iron overload in the genesis of the raised serum ferritin concentrations are confirmed in the diagnostic liver biopsy study. The majority of biopsies showed heavy siderosis, with varying degrees of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Effects of therapy with diet and simvastatin on atherosclerosis in hypercholesterolemic patients.

We evaluated the effect of cholesterol reduction on atherosclerotic coronary artery lesions using diet and simvastatin, a potent HMG CoA reductase inhibitor. Fifteen subjects aged 28-69 years (mean 44), each of whom demonstrated significant (greater than 50%) narrowing of a coronary artery and a baseline cholesterol level greater than 278 mg/dl, were studied. Coronary arteriography was performed prior to and after 20 +/- 2.5 months of therapy. A 42% reduction in total serum cholesterol, a 52% reduction in LDL cholesterol, and an 87% increase in the HDL/LDL cholesterol ratio (p less than 0.01) were achieved. Pretreatment and posttreatment angiograms were reviewed by three experienced angiographers with temporal order masked. Improvement in the overall status of coronary atherosclerotic lesions was demonstrated in two patients (13%), while deterioration occurred in one patient (7%). No overall change was found in the remaining 12 patients (80%). We conclude that a cholesterol-lowering regimen using a nonatherogenic diet and simvastatin therapy may at least stabilize coronary atherosclerosis.

Adult↗
PubMed1989

Iron metabolism in normal and hemochromatotic macrophages.

Certain metabolic pathways of iron were studied in macrophages (cultured human monocytes) obtained from normal and hemochromatotic subjects. The relative abilities of the hydrophobic ferrous chelator 2,2' bipyridine and the hydrophilic ferric chelators desferrioxamine (DFO) and diethylenetriaminepenta-acetic acid (DTPA) to release iron from normal and hemochromatotic macrophages which had previously been loaded with diferric transferrin were tested but there were no differences between the two groups. The relative affinity of the macrophages for diferric transferrin was next studied. Although the hemochromatic macrophages had a somewhat lower affinity for diferric transferrin iron than normal macrophages (Kd 4.7 x 10(-8) M vs. 3.0 x 10(-8)M) the difference did not reach statistical significance (t = 2.01013; P less than 0.07). In a further experiment there was no evidence that apotransferrin was directly involved in the release of iron from hemochromatotic macrophages. A clue to the nature of postendocytotic trans-membrane transport of iron was provided by the finding that it was inhibited by the hydrophobic ferrous chelator 2,2' bipyridine. However, the degree of inhibition was similar in both normal and hemochromatotic macrophages. In summary, none of the metabolic processes examined in the present study was abnormal in cultured human blood monocytes from hemochromatotic subjects.

Dose-Response Relationship, Drug↗
PubMed1989

The fate of intravenously injected tissue ferritin in pregnant guinea-pigs.

The organ distribution of intravenously injected hepatic ferritin either labelled with 59Fe or with 59Fe and 125I, was studied in pregnant guinea-pigs. At 5 h 71.2% of injected 59Fe was present in the placenta and fetus. Transfer of 59Fe to the fetus was slow, with 11.2% present at 5 h and 38.6% at 21 h. Analysis of a placental cellular lysate for 59Fe and 125I revealed that the injected iron was present as intact ferritin at 2 h but by 21 h the ferritin had been catabolized, the 125I excreted and the 59Fe incorporated into endogenous ferritin. Most of the fetal 59Fe counts were detected in the liver, with 35.3% of the transferred 59Fe in ferritin, 30.4% in haemoglobin and 10.6% in a low molecular weight pool. The uptake of labelled ferritin by the placenta was inhibited by a 300-fold molar excess of unlabelled ferritin but not by albumin, asialofetuin or by the injection of carbon particles. A nonsignificant reduction in uptake was noted after injection of mannosylated bovine serum albumin. The mannosidase inhibitor swainsonine had no effect. Iron transfer to the fetus was not affected by various microtubular inhibitors. Presaturation of endogenous transferrin with oral carbonyl iron prevented iron release from the feto-placental unit back into the maternal circulation. In consequence, marrow 59Fe uptake by the maternal marrow was reduced. The ferrous chelator 2,2'-bipyridine significantly reduced 59Fe transfer to the fetus and this occurred irrespective of whether the chelator was given prior to or after 59Fe ferritin administration. The ferric chelator desferrioxamine had no such effect. Electron microscopy of placental tissues revealed endocytosis of ferritin molecules. These results indicate that the guinea-pig placenta takes up homologous tissue ferritin and transfers the iron slowly to the fetus after reductive mobilization. The process is compatible with a receptor-mediated pathway.

Animals↗
PubMed1988

Effect of ferrous and ferric chelators on transferrin-iron-macrophage interactions.

A study was done to evaluate the effect of ferrous and ferric chelators on the interaction between transferrin-iron and cultured human blood monocytes. This interaction has been previously shown to involve a specific receptor and vesicle protonation. Transferrin-iron uptake was significantly inhibited by the hydrophobic ferrous chelator 2,2' bipyridine, and the inhibition was shown not to be a consequence of the mobilisation of intracellular iron by the chelator. Chase experiments and prolonged incubation studies suggested that the chelator prevented the iron released from transferrin from negotiating the unit membrane. The iron and transferrin then appeared to be returned independently to the incubation medium. In contrast, a hydrophilic ferrin chelator, desferrioxamine, had only a very modest effect on the interaction. These findings are compatible with the hypothesis that transferrin-iron is reduced to the ferrous state during its uptake by the culture human blood monocyte.

2,2'-Dipyridyl↗
PubMed1988

Effect of lupines, a protein-rich legume, on iron absorption.

The absorption of iron from lupines, a protein-rich legume, was assessed in 35 parous Indian women. Iron bioavailability was shown to be as low for lupines as soybeans (geometric mean absorptions 0.9 and 1.7 per cent respectively, P less than 0.005). The addition of 30 mg of ascorbic acid moderately improved the geometric mean iron absorption from 1.0 to 5.3 per cent (P less than 0.0001), and 60 mg ascorbic acid from 0.7 to 6.9 per cent (P less than 0.0001). The phytate and polyphenol content of lupines was negligible. The demonstration of poor iron bioavailability from a legume of otherwise rich nutritional potential has important implications in nutritional planning programmes for developing countries.

Dietary Proteins↗
PubMed1983

The genetics and specificity of the constitutive excision repair system of Bacillus subtilis.

An isogenic set of DNA repair-proficient and -deficient strains of B. subtilis, cured of all prophages, were constructed and analyzed for their sensitivities to selected mutagens. The results demonstrated that the lethal damage caused by ultraviolet (UV) radiation and by 4-nitroquinoline-1-oxide (4NQO) were repaired by the bacterial excision and/or recombination repair systems. In contrast, the lethal damages caused by ethyl methane sulfonate (EMS) and methyl methane sulfonate (MMS) were removed from the DNA by the recombination repair system of the bacteria, and not by the excision repair system. Significantly, the bacteria required both a functional recombination repair system and a functional excision repair system in order to remove the DNA damage caused by the bifunctional alkylating agent mitomycin C (MC).

4-Nitroquinoline-1-oxide↗