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Biomedical subjects

S R Cohen

Publications and source records attributed to S R Cohen.

At least 163 records · Page 9Linked to original sources

Vibration syndrome. Cutaneous and systemic manifestations in a jackhammer operator.

Vibration syndrome (VS), which typically presents as a variant of Raynaud's phenomenon, has been characterized recently as a multisystem disorder of the peripheral circulation, nerves, muscles, and joints. The sequelae of the disorder are irreversible, but most clinical evidence indicates that vibration injury is completely reversible by early intervention. Advanced VS occurred in a jackhammer operator; his condition went unrecognized for more than 11 years. The clinical findings illustrate the broad spectrum of pathologic abnormalities associated with VS and emphasize the need for increased physician awareness of this disabling condition.

Diagnosis, Differential↗

"Exchange diffusion": rate equations for the influx of alpha-aminoisobutyric acid into mouse cerebrum slices containing this amino acid.

Rate equations for the gross influx of alpha-aminoisobutyric acid (AIB) into mouse cerebrum slices containing AIB have a first-order term for unsaturable concentrative influx, identical to the corresponding term for unloaded slices, and a modified Michaelis-Menten term, V'max/(1 + Kt/S), for saturable concentrative influx. [V'max identical to v'L(1 + Kt/S), where v'L = saturable component of influx, S = AIB concentration in medium, and Kt = Michaelis constant for unloaded slices.] Below a tissue AIB (T) of 19 mumol/g final wet weight, V'max increases linearly following V'max = V1 + m1T; above that value, Vmax is virtually constant. The transition is sharp. This equation is consistent with a carrier model for active transport. At the transition, intracellular AIB is about 1 molecule for every 70 amino acid residues of tissue protein, vastly more than could be accommodated by AIB-binding sites in cell membranes. The transition may come from a slow process that does not fill all sites when the tissue AIB is below the transition concentration, or from an AIB-induced phase transition in the membrane.

Aminoisobutyric Acids↗

Comparison of left and right ventricular end-systolic pressure-volume relations in congestive heart failure.

A hemodynamic-radionuclide study was performed to compare the relations between end-systolic pressure and volume in the left and right ventricles in 10 patients with biventricular failure, and to correlate the end-systolic pressure-volume slope with baseline variables of systolic function. During nitroprusside or nitroglycerin infusion, or a combination of both, linear relations were found between end-systolic pressure and volume for both ventricles. In 9 of 10 patients, the end-systolic pressure-volume slope was greater for the left ventricle (mean +/- SD 1.12 +/- 0.36 mm Hg X m2/ml) than for the right ventricle (0.46 +/- 0.27 mm Hg X m2/ml) (p less than 0.001). In all 10 patients, the volume-axis intercept of the pressure-volume relation was greater for the left ventricle (82 +/- 66 ml/m2) than for the right ventricle (2 +/- 30 ml/m2) (p less than 0.005). Right ventricular pressure-volume slope correlated weakly with baseline right ventricular ejection fraction (r = 0.69, p less than 0.05), strongly with the baseline right ventricular end-systolic pressure-volume ratio (r = 0.89) and inversely with baseline right ventricular end-systolic volume (r = -0.86). In conclusion, 1) in patients with severe biventricular failure, changes in systolic pressure influence end-systolic volume more strongly in the right than in the left ventricle. 2) For the right ventricle, the slope of the end-systolic pressure-volume relation is directly related to rest indexes of systolic function. 3) The greater the end-systolic volume at rest, the greater the predicted improvement in right ventricular emptying for any vasodilator-induced reduction in pulmonary artery end-systolic pressure.

Adult↗

Rate equations and kinetics of uptake of alpha-aminoisobutyric acid and gamma-aminobutyric acid by mouse cerebrum slices incubated in media containing L(+)-lactate or a mixture of succinate, L-malate, and pyruvate as the energy source.

Influx of alpha-aminoisobutyric acid (AIB) and gamma-aminobutyric acid (GABA) by mouse cerebrum slices incubated with L-lactate or a mixture of succinate, L-malate, and pyruvate (SMP) as the energy source follows the phenomenological rate equation for influx from pyruvate and glucose media: v = Vmax/(1 + Kt/S) + kuS, where v is rate and S is concentration of amino acid. There are two kinetically distinct, parallel components for concentrative uptake, one saturable, and one unsaturable. Rates are less with lactate than with pyruvate and still less with SMP (only GABA was studied), disproving the hypotheses that lower rates with pyruvate compared to glucose are due to an abnormal redox state in the tissue or to a Krebs cycle unbalanced by input at only one point. The carriers for AIB and GABA are qualitatively different. In lactate medium the capacity of each AIB carrier is unchanged but its affinity is reduced to one-third. In lactate and SMP media, the capacity of the saturable GABA carrier is diminished although its affinity is increased. Rates from these media with added glucose or a glucose analog confirm that amino acid and glucose fluxes are not coupled.

Aminoisobutyric Acids↗

The development of constraints on symbol-meaning structure in notation: evidence from production, interpretation, and forced-choice judgments.

Adults use notational systems in a variety of problem-solving situations. For notations to serve the goals we set them, they must conform to certain well-formedness rules, including one-to-one mapping between symbols and meanings and maintenance of the same symbol-meaning relations for both encoding and decoding. Do young children show an appreciation for the utility of notation by adhering to these rules in their production, interpretation, and judgment of notations? Study 1 provides a descriptive analysis of notations created by children aged 5-11 years. Study 2 is a forced-choice task in which preschoolers, 6- and 7-year-olds, and adults chose between a notation that was well-formed according to Goodman's theory of notation and one that violated exactly one of Goodman's principles. The 2 studies present converging evidence that young children may not impose the same symbol-meaning structure at decoding that was set up at encoding, and only after this develops does a preference for one form-one function mapping appear (approximately age 8). Comparisons are made to relevant aspects of the literature on language acquisition.

Age Factors↗

Healing of ischemic colonic anastomoses in the rat: role of antibiotic preparation.

In this study we evaluated the relative effects of ischemia with and without antibiotic bowel preparation on colonic wound healing. Thirty-two Sprague-Dawley rats (185 to 300 gm) were divided into five study groups: Groups I and II (n = 14) had no colonic ischemia, half receiving antibiotic bowel preparation before colocolostomy. Groups III, IV, and V (n = 18) had colonic ischemia induced by division of the marginal artery and ligation of the arteries to the splenic flexure and pelvic colon, assuring that all blood supply to the left side of the colon was intramural. Enteral (neomycin and erythromycin) antibiotic preparation was given in group III, no antibiotics were given in group IV, and parenteral (clindamycin and gentamicin) preparation was given in group V. The mid-left side of the colon was transected and an everting anastomosis was constructed with continuous 6.0 silk sutures. All animals were killed on the seventh postoperative day. Anastomotic healing in unprepared, ischemic rat colon was severely impaired, with an 83% dehiscence rate. In the colon prepared with enteral antibiotics, no adverse effect of ischemia was found. No animal had dehiscence, proximal dilation of the colon, or intra-abdominal abscess. This study may have clinical relevance in patients with ischemic intestinal disorders.

Administration, Oral↗

Yellow staining caused by 4,4'-methylenedianiline exposure. Occurrence among molded plastics workers.

Workers engaged in a molded plastics operation were studied to determine the etiology of yellow staining reactions involving the skin, nails, and hair. A walk-through survey of the facility, medical interviews, physical examinations, and blood and urine tests were performed. 4,4'-Methylenedianiline (MDA), a component chemical of the manufacturing process, produced intense yellow discoloration of nitrocellulose paper in the laboratory and appeared to volatilize readily under ambient conditions. Thirty-five (65%) of 54 process workers showed varying degrees of staining while 11 workers employed in other parts of the factory showed no staining. Yellow staining was restricted to areas of the body where direct contact with MDA appeared likely. Laboratory studies did not provide evidence of systemic toxic effect. Because MDA is a known hepatotoxin for man, with carcinogenic properties in animal test systems, it is important to recognize yellow staining as a cutaneous marker of exposure to this chemical.

Adult↗

Late (5 to 132 months) clinical and hemodynamic results after either tricuspid valve replacement or anuloplasty for Ebstein's anomaly of the tricuspid valve.

Late clinical and hemodynamic observations are described in 6 patients who had either tricuspid valve anuloplasty (TVA) (2 patients) or tricuspid valve replacement (TVR) (4 patients) 5 to 132 months earlier for Ebstein's anomaly of the tricuspid valve unassociated with right ventricular outflow obstruction. Of the 6 patients, 4 had improved postoperatively by 1 New York Heart Association functional class and 2 had improved by 2 functional classes. The cardiothoracic ratio decreased 5 to 12 months after either TVR or TVA in all 6 patients (from a mean of 0.72 to 0.62). Repeat cardiac catheterization 5 to 12 months after TVA or TVR disclosed that the right atrial mean pressure had increased from a median of 4.0 to 10.5 mm Hg (p = 0.05); the right ventricular peak systolic pressure had increased from 19.0 to 31.5 mm Hg (p = 0.02); the right ventricular end-diastolic pressure had increased from 5.0 to 9.0 mm Hg (p = 0.05); the systemic arterial peak systolic pressure had increased from 115 to 123 mm Hg (p = 0.03); and the cardiac index had increased (in all 4 patients in whom both pre- and postoperative values were available) from 1.7 to 2.9 liters/min/m2 (p = 0.06). Thus, the tricuspid valve operations in our 6 patients with Ebstein's anomaly were associated with a decrease in symptoms of cardiac dysfunction, a decrease in cardiac size, an increase in cardiac index and an increase in right ventricular and right atrial pressures. The elevation of the right atrial pressures postoperatively may have resulted from increased right ventricular filling pressures, persistent tricuspid regurgitation or bioprosthetic stenosis.

Adolescent↗

Vasodilator effect on right ventricular function in congestive heart failure and pulmonary hypertension: end-systolic pressure--volume relation.

The right ventricular (RV) end-systolic pressure-volume relation during vasodilator administration was studied in 10 patients with pulmonary arterial (PA) hypertension, most of whom had biventricular failure. RV end-systolic volumes were estimated from equilibrium radionuclide RV counts and forward cardiac output. Simultaneous radionuclide and hemodynamic values were measured at rest and during nitroglycerin and nitroprusside infusion. Vasodilator administration resulted in decreases in PA mean and systolic pressures in all 10 patients, with an average decrease in end-systolic pressure (p less than 0.001) from 48 +/- 11 to 38 +/- 9 and 35 +/- 10 mm Hg during nitroglycerin and nitroprusside administration, respectively. In each patient, a direct linear relation was observed between the vasodilator-induced decrease in PA end-systolic pressure and in RV end-systolic volume. Average RV end-systolic volume decreased (p less than 0.001), from 130 +/- 69 ml/m2 at baseline to 108 +/- 62 and 102 +/- 55 ml/m2 during nitroglycerin and nitroprusside infusion, respectively. The slope of the RV end-systolic pressure-volume relation was directly related to RV ejection fraction. Thus, the vasodilator-induced decrease in PA systolic pressure is accompanied by a linear decrease in RV end-systolic volume, with a slope which is dependent on RV systolic function. This linear relation is analogous to the left ventricular end-systolic pressure-volume relation.

Adult↗

Unilateral analgesia produced by intraventricular morphine.

Morphine injected into the lateral ventricle of the rat produced unilateral analgesia in the formalin test, which involves continuous, moderate pain. In contrast, analgesia was produced bilaterally in the foot-flick test which involves brief, rapidly rising pain. In the formalin test, intraventricular morphine produced analgesia in the ipsilateral but not the contralateral hindpaw. Analgesia was achieved with relatively low doses of morphine (2.5-10.0 micrograms) in the formation test while very high doses (50-200 micrograms) were necessary to produce analgesia in the foot-flick test. These results add to other data indicating that different neural mechanisms underlie opiate analgesia in different types of pain. Moreover, they indicate that, in the formation test, the neural mechanisms of morphine analgesia are somatotopically organized and that forebrain structures are likely to be involved.

Animals↗

Comparison of late (62 to 140 months) degenerative changes in simultaneously implanted and explanted porcine (Hancock) bioprostheses in the tricuspid and mitral valve positions in six patients.

A Hancock porcine bioprosthesis (PB) was simultaneously implanted in each of 6 patients aged 30 to 64 years (mean 45) in the tricuspid and mitral valve positions and both PBs were explanted 62 to 140 months (mean 102) later. Cuspal degenerative changes occurred in all 12 PBs. In 5 patients, the changes were more extensive on the PBs in the mitral position than in those in the tricuspid position. Cuspal calcific deposits, as determined by radiographs of the explanted bioprostheses, occurred in 5 PBs in the mitral position and in 3 in the tricuspid position: 1 patient with calcific deposits in the PB in the mitral position had no calcific deposits in the corresponding PB in the tricuspid position; 1 patient had heavy calcific deposits in the PB in the mitral position and only mild deposits in the PB in the tricuspid position; and 3 patients had similar but mild calcific deposits in both PBs. Cuspal tears occurred in 5 of the 6 PBs in the mitral position and in no PB in the tricuspid position. Thrombus was observed on the ventricular aspects of the bioprosthetic cusps in 1 PB in the mitral position and in 4 PBs in the tricuspid position. Thus, in our 6 patients, the degenerative changes were more extensive in the PBs in the mitral position than in those in the tricuspid position. These observations indicate that wear characteristics of simultaneously implanted PBs vary according to the site of implantation.

Adult↗

Treatment of the cbl B form of methylmalonic acidaemia with adenosylcobalamin.

A 30-month-old girl was found to have the cbl B mutant form of methylmalonic aciduria by complementation analysis of fibroblasts. She was unresponsive to hydroxycobalamin and was treated with intramuscular adenosylcobalamin (AdoCbl), the deficient coenzyme, at a dose of 1 mg/24h during a period of clinical stability. Serum cobalamin increased from 770 to 54 200 pg/ml. Mean urinary methylmalonic acid excretion was 409 mg/24 h prior to therapy. There was a transient fall in methylmalonic acid excretion during the first 5 days of therapy (range 167-245 mg/24h) followed by a rise in excretion toward pretreatment levels (range 317-485 mg/24h) during the second week of AdoCbl treatment. There was no change in plasma ammonia, glycine or serum bicarbonate level. We interpret the failure of this child to have a sustained and clinically significant response to AdoCbl as indicating that AdoCbl did not reach or enter the mitochondria intact, or in some other way was unavailable as a coenzyme for the methylmalonyl CoA mutase apoenzyme.

Amino Acid Metabolism, Inborn Errors↗

Bullous lichen sclerosus et atrophicus: treatment by tangential excision.

The bullous variant of lichen sclerosus et atrophicus (LSA) is a rare disorder for which there is no satisfactory treatment. A patient is reported with extensive plaques of bullous LSA on the pretibial skin that did not respond to sharp debridement, vigorous local care, or intralesional corticosteroid injections. Tangential partial-thickness excision of diseased tissues resulted in an extended remission. To our knowledge this approach has not been previously employed for bullous LSA, and it offers an encouraging surgical alternative to other therapeutic modalities.

Aged↗

Elevated myelin basic protein levels in the cerebrospinal fluid of children with acute lymphoblastic leukemia.

Cerebrospinal fluid was examined from 70 children with acute lymphoblastic leukemia for evidence of active myelin breakdown based on the release of myelin basic protein (MBP). Fifty-three asymptomatic children were followed from diagnosis with serial MBP determinations. Eight (15.1%) of 53 children had abnormal elevations of MBP, six of eight before receiving presymptomatic central nervous system therapy. Long-term observations are in progress. For comparison, six children with clinical and radiologic findings of leukoencephalopathy had abnormal MBP determinations, whereas no abnormalities were detected in 11 children with meningeal leukemia.

Adolescent↗

Clinical and morphologic cardiac findings after anthracycline chemotherapy. Analysis of 64 patients studied at necropsy.

The relation between clinical evidence of and histologic signs of anthracycline cardiotoxicity was evaluated by reviewing the clinical and morphologic findings in 64 patients studied at necropsy, all of whom had received doxorubicin or daunorubicin chemotherapy during life. Of the 64 patients, 20 (31%) had documented clinical toxicity consisting of impaired left ventricular systolic performance; in 7 (35%) of these 20 patients, histologic signs of toxicity were absent. In the remaining 13 patients with clinical toxicity, histologic signs of toxicity ranged from mild to severe. Of the 44 (69%) patients without clinical signs of drug toxicity, 21 (48%) had no histologic sign of cardiotoxicity; in 23 (52%) of the patients without clinical toxicity, however, morphologic signs of cardiotoxicity were nevertheless present--mild in most patients, but extensive in 4. Signs of extensive histologic toxicity (19 [30%] of 64 patients) were associated with large doses (greater than 450 mg/m2) of the drug, mediastinal irradiation, and age greater than 70 years. This study suggests that attempts to monitor cardiotoxicity by serial evaluation of cardiac histology in patients undergoing anthracycline chemotherapy may be seriously limited by the fact that clinical evidence of toxicity may be present without histologic signs of toxicity; likewise, histologic signs of anthracycline toxicity may be present without clinical evidence of toxicity.

Adolescent↗