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Biomedical subjects

A M Stern

Publications and source records attributed to A M Stern.

At least 55 records · Page 3Linked to original sources

DL-threo-beta-Fluoroaspartate and DL-threo-beta-fluoroasparagine: selective cytotoxic agents for mammalian cells in culture.

Absolute configuration assignments have been made for the diastereomers of DL-beta-fluoroaspartate by X-ray analysis. The cytotoxicity of these isomers against various mammalian cells was examined. DL-threo-beta-Fluoroaspartate shows selective cytotoxicity. Growth of the most sensitive cells is completely inhibited by 13 micrometers DL-threo-beta-fluoroaspartate in the presence of 100 micrometers L-aspartate, a component of the culture medium. A difference in the rate of transport of DL-beta-fluoroaspartate among the cells studied is an important factor determining cell specificity. For those cells that are sensitive to DL-beta-fluoroaspartate, the threo isomer is, in all cases, more potent than the erythro isomer. Radioactivity derived from L-threo-beta-fluoro[14C]aspartate is incorporated into proteins at a rate comparable to the rate of incorporation from L-[14C]aspartate. We synthesized DL-threo-beta-fluoroasparagine. This compound is also cytotoxic but less specific and less potent than DL-threo-beta-fluoroaspartate. However, the cell specificity can be enhanced in the presence of 1 mM L-aspartate, which can protect some cells but not others from the cytotoxic effects of DL-threo-beta-fluoroasparagine. Jensen sarcoma cells, which require asparagine, are not protected by L-aspartate. Therefore, a combination of L-aspartate and DL-threo-beta-fluroasparagine can be used to inhibit specifically the growth of asparagine-requiring tumors.

Amino Acids↗

Ventricular pacing in children.

Ventricular pacing was performed in forty-one children ranging from one day to twenty years of age (median age = 10). Weight of the recipient at implant ranged from 2 kg. to 86 kg. Indications included presyncope, syncope, dyspnea on exertion, congestive heart failure, postoperative infra-Hisian heart block, and inadequate cardiac rate during pharmacotherapy. Four patients died during follow-up, but no deaths were attributable to pacemaker management. In contrast, 66% of the patients required more than one pacemaker related-operative procedure, and 43% of leads implanted failed by 48 hours. Indications for permanent cardiac pacing in this population at this time are symptomatic congenital AV block, symptomatic sinus node disease, and AV block in the postoperative period. Technological developments which might reduce complications seen in this population and electrophysiologic techniques which may better define indications for pacing in children are also reviewed.

Adolescent↗

Pulmonary lymphangiectasis in Noonan syndrome.

This report describes the course and prognosis of four patients with Noonan syndrome and associated pulmonary lymphangiectasia. All patients had (1) superior deviation of the QRS axis in the frontal plane of the electrocardiogram; (2) moderate to severe valvular pulmonary stenosis, with an additional atrial septal defect secundum type present in two and a small ventricular septal defect in one; and (3) bilateral prominence of the pulmonary interstitial markings (dilated lymphatics), with or without accompanying pleural effusions on the chest radiographs. Surgical repair of the cardiac lesion may cause undue morbidity because of the interruption of the engorged pleural or mediastinal lymphatics.

Adult↗

Estimation of pulmonary/systemic resistance ratios from echocardiographic systolic time intervals in young patients with congenital or acquired heard disease.

Previous work has shown the positive correlation of echocardiographic right ventricular preejection period/right ventricular ejection time ratio (RPEP/RVET) with pulmonary vascular resistance and pulmonary arterial diastolic pressure obtained at cardiac catheterization. However, the correlation was insufficient to predict pulmonary arterial diastolic pressure or vascular resistance from a given RPEP/RVET ratio. In this study the RPEP/RVET ratio was compared with left ventricular preejection period/ejection time ratio (LVEP/LVET) in 25 patients undergoing cardiac catheterization, and a strong correlation was found between the ratio (RPEP/RVET)/(LPEP/LVET) = R/L and the ratio of pulmonary arteriolar resistance/systemic arteriolar resistance (PAR/RS), especially when R/L was correlated with log10 PAR/RS (r = 0.902). A very high correlation (r = 0.960) was found between R/L and log10 PAR/RS when the group was restricted to patients with a ventricular septal defect or a complete endocardial cushion defect. Regression equations for prediction of PAR/RS have been derived for the various groups.

Adolescent↗

Ventricular septal defect: results after repair in infancy.

During the 19 years from 1957 through 1975, there have been 106 patients under age 2 years who have undergone surgery for repair of a large ventricular septal defect at the University of Michigan Medical Center. The majority of the patients had either severe pulmonary hypertension or intractable congestive heart failure. Eighty-three infants survived operation; there has been one late death. The greatest mortality occurred in patients under age 6 months and in those with severe pulmonary hypertension. Surviving infants showed marked symptomatic improvement and change in growth patterns. Complications included the development of complete right bundle branch blodk or left anterior hemiblock in approximately 50 percent of patients and, in one instance, complete atrioventricular block. Forty-five patients have undergone cardiac catheterization 1 to 8 years postoperatively. Although 17 were found to have residual septal defects only 3 of these had a pulmonary to systemic flow ratio of 1.5:1 or more, and reoperation was accomplished without incident in these 3 patients and in 3 others with smaller shunts. With one exception, postoperative pulmonary arterial pressures and pulmonary to systemic vascular resistance ratios were normal or near normal, thus representing a significant contrast with findings in patients operated on after age 2 years. Whereas the complications of surgery appear no greater in the infant than in the older patient, many of the benefits can be realized only with operation at the earlier age.

Cardiac Catheterization↗

Diagnosis of pericardial effusion in children: a new radiographic sign.

A band of increased density paralleling the left lower border of the cardio-pericardial silhouette is seen on anteroposterior chest films in some children with pericardial effusions. To analyze the incidence and accuracy of this sign, films of children with pericardial effusions and controls were compared. Among 17 children with proved pericardial effusion, bands of density within the cardio-pericardial silhouette were seen in six films, while positive epicardial fat pad signs were seen on four. When three radiologists without experience in use of the sign evaluated radiographs of the six patients with the sign and six controls without pericardial effusion, the sign was detected in most instances in the children with effusions (specificity and sensitivity, 83%). In vitro studies of unpreserved hearts in baths of solutions of varying osmolarity failed to show detectable differences in density between myocardium and any of the solutions. We conclude that the new sign may be produced by epicardial fat adjacent to pericardial fluid.

Humans↗

A different approach for the total correction of tricuspid atresia.

A new surgical procedure has been used successfully to correct tricuspid atresia in a 9-year-old girl. An external conduit containing a porcine aortic valve was positioned to lead from the right atrium to the underdeveloped right ventricle. The right ventricle was reconstructed with a large Dacron patch, thus providing a large cavity for the small hypoplastic right ventricle. The atrial and ventricular septal defects were closed. The patient made a satisfactory recovery and is doing well four months after the operation.

Cardiac Catheterization↗