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Biomedical subjects

M D Feldman

Publications and source records attributed to M D Feldman.

At least 73 records · Page 4Linked to original sources

Bolus intravenous nitroglycerin predominantly reduces afterload in patients with excessive arterial elastance.

OBJECTIVES: We hypothesized that bolus intravenous nitroglycerin would be an afterload-reducing agent in patients with excessive initial afterload for their level of left ventricular systolic function. Conversely, bolus intravenous nitroglycerin should be a preload-reducing agent in patients without excessive initial afterload. BACKGROUND: Although nitroglycerin has both preload- and afterload-reducing actions, methods to predict its predominant site of action in an individual patient have not been previously described. METHODS: Left ventricular pressure-volume relations were recorded with micromanometer and conductance catheters during bolus injection of intravenous nitroglycerin in 27 patients with both normal left ventricular systolic function and varying degrees of congestive heart failure. Preload was determined by end-diastolic volume, afterload by effective arterial elastance, left ventricular systolic function by end-systolic elastance and coupling of afterload and ventricular function by the ratio of effective arterial elastance to end-systolic elastance (Ea/Ees ratio). An Ea/Ees ratio > 1 was defined as excessive afterload for the level of ventricular function. RESULTS: Patients with an initial Ea/Ees ratio < 1 (Group 1) constituted a group of normotensive patients with intact ventricular function who exhibited a predominant reduction in preload in response to intravenous nitroglycerin. Those with an initial Ea/Ees ratio > 1 and normal or mildly depressed ventricular function (Group 2a) constituted a group of patients, most of whom were hypertensive, who exhibited a predominant afterload reduction. Finally, those with an initial Ea/Ees ratio > 1 and abnormal ventricular function (Group 2b) constituted a group of patients with clinical congestive heart failure who exhibited both preload and afterload reduction but a predominant afterload reduction because stroke volume increased. CONCLUSIONS: Patients with normal arterial elastance and ventricular function respond to nitroglycerin with a predominant preload reduction, whereas patients with either excessive arterial elastance or abnormal ventricular function respond with a predominant afterload reduction.

Analysis of Variance↗

Why do patients with congestive heart failure tolerate the initiation of beta-blocker therapy?

BACKGROUND: Despite its negative inotropic effects, the initiation of beta-adrenergic blockade is tolerated by patients with congestive heart failure (CHF). Accordingly, we examined the acute hemodynamic effects of beta-adrenergic blockade on systolic and diastolic left ventricular (LV) function and ventriculo-arterial coupling. In addition, isolated myocardium from patients with CHF shows selective beta 1-receptor downregulation, implying a greater role for the beta 2-receptor in maintaining in vivo LV contractility. As a secondary aim, we hypothesized that nonselective beta-adrenergic blockade would have greater negative inotropic effect than beta 1-blockade in patients with CHF. METHODS AND RESULTS: Patients with clinical CHF (n = 24) and control patients without CHF (n = 24) were given either the nonselective beta-blocker propranolol or the beta 1-selective blocker metoprolol. LV pressure-volume relations were obtained before and after the administration of intravenous beta-blocker, and measures of LV systolic and diastolic function were examined. Patients with CHF had a deterioration in LV systolic function with a fall in LV systolic pressure (139 +/- 6 to 125 +/- 6 mm Hg), cardiac index (2.56 +/- 0.11 to 2.20 +/- 0.11 mL.min-1 x M-1), dP/dtmax (1173 +/- 63 to 897 +/- 50 mm Hg/s), and end-systolic elastance (0.88 +/- 0.10 to 0.64 +/- 0.10 mm Hg/mL), P < .05 for all. Although there was deterioration of active LV relaxation (isovolumetric relaxation 63 +/- 2 to 73 +/- 3 milliseconds, peak filling rate 543 +/- 33 to 464 +/- 28 mL/s, P < .05 for both), there was no change in passive LV diastolic function (pulmonary capillary wedge, 24 +/- 2 to 24 +/- 1 mm Hg; chamber stiffness, 0.0154 +/- 0.0005 to 0.0163 +/- 0.0005 mL-1, P = NS for both), and a decrease in afterload (arterial elastance 3.85 +/- 0.31 to 3.38 +/- 0.24 mm Hg/mL, P < .05). Control patients had no change in these parameters other than a prolongation of isovolumetric relaxation (48 +/- 1 to 55 +/- 2 milliseconds, P < .05). The effects of propranolol (n = 12) versus metoprolol (n = 12) on these parameters in patients with CHF were similar. CONCLUSIONS: These data do not support a greater in vivo physiological role of the myocardial beta 2-receptor in CHF. The preservation of passive diastolic function and ventriculo-arterial coupling provide possible explanations of why beta-adrenergic blockade is tolerated by patients with CHF.

Adrenergic beta-Antagonists↗

Use of the metaphyseal-diaphyseal angle in the evaluation of bowed legs.

We evaluated the accuracy of the angle described by Levine and Drennan, the metaphyseal-diaphyseal angle of the proximal aspect of the tibia, for the differentiation of physiological bowing from Blount disease. We compared this angle, as measured at presentation, in 106 children (179 extremities) who had physiological bowing with the angle in nineteen children (thirty-two extremities) who had documented Blount disease. The angle averaged 9 +/- 3.9 degrees for the patients who had physiological bowing and 19 +/- 5.7 degrees for the patients who had Blount disease (p < 0.0000001). Linear regression analysis, performed to evaluate any changes in the metaphyseal-diaphyseal angle in relation to age, showed that the older the child was at the time of presentation the more likely it was that the angle would be smaller in a child who had physiological bowing and larger in a child who had Blount disease. The chance for false-positive and false-negative errors was greater than 5 per cent if the angle was more than 9 degrees but less than 16 degrees. Sixty-six (37 percent) of the 179 extremities in the group that had physiological bowing had an angle of at least 11 degrees; one extremity affected by Blount disease had an angle of less than 11 degrees. In this study, we found that the metaphyseal-diaphyseal angle may be helpful in the identification of Blount disease but should not be the sole criterion used to determine the diagnosis.

Age Factors↗

Hyndman-Schneider procedure for paraplegia caused by a sharp, angular scoliosis: a case report and a review of the literature.

Scoliosis causing neurologic deficit is rare. Nonoperative treatment has been shown to be unsuccessful in reversing the condition or preventing further neurologic progression. Surgical intervention using the Hyndman-Schneider approach (costotransversectomy and apical pedicle resection) decompresses the spinal cord by transposing it into the concavity of the deformity. Although it is a demanding procedure with significant risks, lateral spinal cord transposition is the preferable procedure to provide full neurologic recovery in successful cases.

Adolescent↗

The precise radioimmunoassay of adenosine: minimization of sample collection artifacts and immunocrossreactivity.

Anti-adenosine antibodies were produced in rabbits immunized with N6-carboxymethyladenosine conjugated to methyl albumin. 125I-N6-Aminobenzyladenosine was synthesized and used as a high-specific-activity, high-affinity ligand. A radioimmunoassay (RIA) was developed that can detect 6.25 nM (312.5 fmol) of underivatized adenosine and cross-reacts less than 0.02% with adenine nucleotides and guanosine and not at all with 1 mM inosine. The sensitivity of the RIA can be increased to a detection limit of 0.125 nM (6.25 fmol) by derivitizing samples with benzyl bromide to form N6-benzyladenosine. The assay was adapted to an automated RIA procedure. Assay precision was increased by: (i) inhibiting slight adenosine deaminase activity present in anti-sera; (ii) treating buffers and albumin used in the RIA with charcoal to remove contaminating adenosine; and (iii) correcting for a small but variable component of immunoreactivity not attributable to adenosine. A second antibody prepared with a 2',3'-disuccinyladenosine-albumin conjugate was also found to detect some non-adenosine-mediated immunoreactivity in plasma samples. Immunointerference in human plasma was eliminated in samples treated with ZnSO4/Ba(OH)2 or partially purified over C18 Sep Paks to remove nucleotides and assayed after sample benzylation or succinylation. Human blood was mixed with a novel "stop" solution that was optimized to inhibit adenosine formation from AMP by greater than 99% and to inhibit adenosine uptake into red cells and degradation by greater than 94%. Human plasma/stop solution was assayed by RIA and HPLC with equivalent results.

Adenine↗

Self-mutilation.

Explore the source record for details and available documents.

Adult↗

Improved detection of ischemia-induced increases in coronary sinus adenosine in patients with coronary artery disease.

Attempts to monitor coronary sinus adenosine as a clinical marker of myocardial ischemia in humans have been disappointing. Accordingly, procedures have been developed for detecting adenosine in blood collected from the human coronary sinus. Collection involves using a double-lumen metabolic catheter, which allows blood to be mixed with a stop solution at the catheter tip, thereby minimizing adenosine formation and degradation. A five-component stop solution almost completely arrests adenosine formation and degradation. Adenosine analysis is improved by using both boronate and C18 Sep-Pak columns to purify and concentrate adenosine in human plasma before HPLC. Plasma adenosine in the coronary sinus of patients with and without coronary artery disease, measured before and during peak atrial pacing, showed a twofold atrial pacing-induced increase in adenosine in the patients with coronary artery disease (n = 9, P less than 0.001) but no change in the patients with normal epicardial coronary arteries (n = 6). These preliminary results indicate that coronary sinus adenosine may provide an index of myocardial ischemia in patients with coronary artery disease.

Adenosine↗

Influence of contrast media on thrombus formation during coronary angioplasty.

The influence of contrast media on thrombus formation during percutaneous transluminal coronary angioplasty was assessed in 124 consecutive patients undergoing coronary angioplasty and receiving either ionic (n = 57) (Group I) or nonionic (n = 67) (Group II) contrast medium. The presence of thrombus was assessed by qualitative analysis of angiograms in identical pre- and postangioplasty projections by four observers who had no knowledge of other data. Quantitation of stenosis severity before and after angioplasty and qualitative analysis of lesion eccentricity and complexity and of the presence of dissection were also performed. Although the baseline clinical characteristics of the two groups (including presenting syndromes and procedural and angiographic variables) did not differ, more patients in Group II than Group I developed new thrombus during coronary angioplasty (18% vs. 4%, p less than 0.02). In particular, patients with a presenting syndrome of recent myocardial infarction or rest angina, or both, and patients with an eccentric coronary plaque were more likely to develop new thrombus if they received nonionic than if they received ionic contrast medium (p less than 0.05). Patients with new thrombus formation and patients with thrombus present both before and after angioplasty had a high incidence of acute procedural complications (36% and 23%, respectively). Patients in Groups I and II had a similar incidence of ischemic events during follow-up.

Angioplasty, Balloon, Coronary↗

Factitious cyclic hypersomnia: a new variant of factitious disorder.

The central goal of patients with factitious disorders is to receive medical care. Unnecessary diagnostic procedures and recurrent hospitalizations often ensue. We saw a 39-year-old man with a novel variation of this disorder: factitious cyclic hypersomnia, or the simulation of recurrent episodes of excessive sleep. This case highlights the observations that patients whose illnesses are simulated may have diverse symptoms, that no syndrome is immune to factitious imitation, and that attempts at treatment, though exceedingly challenging, are always contingent upon appropriate recognition.

Adult↗

Diastolic dysfunction in hypertrophic cardiomyopathy. Effect on active force generation during systole.

We tested the hypothesis that intracellular Ca++ [( Ca++]i) overload underlies the diastolic dysfunction of patients with hypertrophic cardiomyopathy. Myocardial tissue was obtained at the time of surgery or transplantation from patients with hypertrophic cardiomyopathy and was compared with control myocardium obtained from patients without heart disease. The isometric contractions and electrophysiologic properties of all myocardial specimens were recorded by standard techniques and [Ca++]i was measured with the bioluminescent calcium indicator aequorin. In contrast to the controls, action potentials, Ca++ transients, and isometric contraction and relaxation were markedly prolonged in the hypertrophic myocardium, and the Ca++ transients consisted of two distinct components. At 38 degrees C and 1 Hz pacing frequency, a state of relative Ca++ overload appeared develop, which produced a rise in end-diastolic [Ca++]i, incomplete relaxation, and fusion of twitches with a resultant decrease in active tension development. We also found that drugs with increase [Ca++]i, such as digitalis, exacerbated these abnormalities, whereas drugs that lower [Ca++]i, such as verapamil, or agents that increase cyclic AMP, such as forskolin, prevented them. These results may explain why patients with hypertrophic cardiomyopathy tolerate tachycardia poorly, and may have important implications with regard to the pharmacologic treatment of patients with hypertrophic cardiomyopathy.

Adult↗

Post-extrasystolic potentiation and the force-frequency relationship: differential augmentation of myocardial contractility in working myocardium from patients with end-stage heart failure.

We studied post-extrasystolic potentiation (PESP) and frequency potentiation (FP) of human working myocardium isolated from the ventricles of 10 patients with end-stage heart failure (CHF) and 17 non-failing controls (CTL). The contractility index was peak isometric tension developed in vitro by trabeculae carneae (CTL n = 34, CHF n = 31); programmed electrical stimulation was used to initiate as well as alter the timing relationship of the contractile events. While holding constant the total number of contractions per unit of time, we compared the augmentation of contractile performance that occurred upon doubling the stimulation frequency (FP) to that of changing the stimulation pattern (PESP). In the CTL group we found that FP and PESP differed in their ability to augment cardiac contractile performance, PESP being more effective; 105 +/- 13% for PESP vs. 34 +/- 11% (mean +/- S.E.M.) for FP. In the CHF group, the inotropic response to PESP was similar to CTL; in contrast, the relative efficacy of FP (3 +/- 3%) compared to PESP (81 +/- 14%) was markedly diminished. Studies with positive inotropic agents revealed that the percent change in contractility induced by FP and PESP depends upon the relative inotropic state of the heart; however, the contractile response to PESP always equaled or exceeded those produced by clinically relevant concentrations of inotropic agents, particularly in CHF muscles. Agents that increase intracellular levels of adenosine 3',5'-cyclic monophosphate reversed the FP abnormalities seen in the CHF group, suggesting that deficient production of this second messenger in heart failure may cause the abnormal force-frequency relationship in failing myocardium. We conclude that the differential responses of myopathic muscle to PESP and FP may be caused by abnormal restitution processes during diastole. Our results suggest that PESP may be an effective therapeutic modality for patients with severe heart failure who have failed to adequately respond to inotropic drugs, and may serve as a useful indicator of cardiac contractile reserve in these patients.

Assisted Circulation↗

Sequelae of attempted suicide by cyanide ingestion: a case report.

A twenty-eight-year-old man presented emergently after ingesting 800 mg of potassium cyanide in a suicide attempt. He survived only with intensive medical and psychiatric intervention, and went on to develop severe parkinsonian symptoms, including profound micrographia and hypersalivation. Bilateral, symmetrical basal ganglial abnormalities were demonstrated with magnetic resonance imaging. Survival following cyanide poisoning is rare; the clinical, radiologic, and neuropathologic sequelae in other documented cases are reviewed.

Adult↗