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Biomedical subjects

J Levin

Publications and source records attributed to J Levin.

At least 145 records · Page 8Linked to original sources

Solitary thick intra-uterine membranes not associated with the amniotic band syndrome; three case reports.

Three cases in which a single intra-uterine membrane with a free and thickened edge was identified by ultrasound antenatally are presented. The bands turned out to be thickenings of the fetal membranes. In one case intra-uterine adhesions were documented by hysterosalpingography (HSG) and hysteroscopy before conception. One infant suffered from hypospadias. The diagnosis of intra-uterine bands or membranes should turn our attention to a possible intra-uterine pathology.

Adult↗

Adverse effects of antibiotics.

Adverse reactions to antibiotics comprise a number of classes of reactions, including toxicity, side effects, and allergy. Each one of these differs in its implication for treatment of the patient. The authors discuss some of the more common and unusual reactions to antibiotics frequently used in the practice of podiatric medicine.

Anti-Bacterial Agents↗

Measurement of megakaryocyte frequency and ploidy distribution in unfractionated murine bone marrow.

Measurement of megakaryocyte frequency, ploidy distribution, and maturation stage have been complicated by the low frequency of megakaryocytes in either bone marrow or spleen. Due to harsh labeling conditions, previous studies utilizing flow cytometry have not quantified cell recovery or megakaryocyte frequency. We have modified our two-color fluorescence-activated cytometric technique in order to identify megakaryocytes in unfractionated murine bone marrow with a fluoresceinated cell surface immunologic probe (heterologous polyclonal platelet antiserum) and to selectively measure megakaryocyte DNA content with propidium iodide using isosmolar conditions. Under these conditions, total nucleated cell recovery from unfractionated normal murine bone marrow, after all preparative procedures, averaged 68.0% +/- 5.0% (SD) with 93.5% +/- 2.0% DNA staining efficiency. Mean megakaryocyte frequency (n = 30) was 0.14% +/- 0.04%. Using both our previously described gating technique with single parameter analysis and our modified dual parameter technique, the modal megakaryocyte ploidy class was 16N. Low ploidy megakaryocytes, 2N and 4N, constituted 9.8% and 10.8%, respectively, of the total megakaryocyte population. Analysis of the megakaryocyte population with respect to cell surface fluorescence intensity demonstrated that the dimly fluorescent population contained an increased proportion of lower ploidy class cells (2N + 4N + 8N) compared with brightly fluorescent cells, which contained an increased proportion of higher ploidy cells (16N + 32N). Our modifications of the two-color technique yielded improved recovery of total nucleated bone marrow cells from unfractionated bone marrow and provided more precise measurements of megakaryocyte frequency and ploidy than previously available.

Animals↗

A randomized clinical trial of 10% pentastarch (low molecular weight hydroxyethyl starch) versus 5% albumin for plasma volume expansion after cardiac operations.

Pentastarch is a hydroxyethyl starch similar to hetastarch, but with a lower average molecular weight (264,000 versus 450,000) and fewer hydroxyethyl groups (molar substitution ratio = 0.45 versus 0.70). These characteristics result in enhanced enzymatic hydrolysis, faster renal elimination (initial intravascular half-life = 2.5 versus 25.5 hours), and less effect on coagulation. We report on a randomized clinical trial comparing the clinical efficacy and safety of 10% pentastarch (group P) for plasma volume expansion after cardiac operations with that of 5% serum albumin (group A). During the first 24 hours after arrival of the patient in the intensive care unit, colloid was infused to maintain a cardiac index of 2.0 L/m2 or more and a mean arterial pressure within 10% of the preinduction value. Group P (n = 50) received 1706 +/- 393 ml of colloid (mean +/- standard deviation) during this period, and group A (n = 44), 1794 +/- 341 ml (p = no significant difference). Hemodynamic responses to infusion were similar for both groups, although in group P a greater increase in both cardiac index (0.5 +/- 0.5 versus 0.3 +/- 0.5 L/min/m2 in group A, p less than 0.01) and left ventricular stroke work index (10.8 +/- 8.0 versus 5.8 +/- 6.0 gm-m/m2, p less than 0.01) was observed during infusion of the first 500 ml. There were no significant differences in any of the measured respiratory parameters (alveolar-arterial oxygen gradient, estimated shunt fraction, and effective pulmonary compliance). Hemodilution with colloid significantly reduced serum protein levels in group P by 24 hours postoperatively (4.0 +/- 0.6 versus 5.0 +/- 0.7 gm/dl in group A, p less than 0.05), although mean serum colloid osmotic pressure was similar (15.4 +/- 2.6 [P] versus 15.5 +/- 2.7 mmHg [A], p = no significant difference). There were no significant between-group differences in prothrombin time, activated partial thromboplastin time, platelet count, bleeding time, or coagulation factors (fibrinogen, V, VII, VIII, or IX) on postoperative days 1 and 7. Perioperative fluid balance, weight change, chest tube output, red blood, platelet, or fresh frozen plasma usage, reexploration for bleeding, and clinical outcome were also similar. These findings indicate that pentastarch is as safe and effective s 5% albumin for plasma volume expansion after cardiac operations with no apparent adverse effects on coagulation. If commercially available at a lower cost than albumin, it would appear to be a reasonable first choice for colloid therapy in this setting.

Aged↗

Effect of detoxification processes on the interferon-inducing activity of bacterial endotoxins.

The interferon (IFN)-inducing activity of detoxified lipopolysaccharide (LPS) was tested in rabbits treated with LPS preparation derived from Escherichia coli, Salmonella typhi, Salmonella enteritidis and Shigella dysenteriae serovar 1. Of the detoxification procedures used, alkaline hydrolysis, hydroxylaminolysis, formalization, treatment with sodium deoxycholate and the radiodetoxification (fast or slow) methods had no appreciable effects on the IFN-inducing potential of LPS. In contrast, acetylation or prolonged alkaline hydrolysis of LPS resulted in up to a 9-fold reduction of IFN-induction capacity and effects of Cu++ or Fe++ cations bound to LPS were clearly inhibitory (Fe more than Cu).

Acetylation↗

Ciliary sulcus reconstruction for posterior implantation in the absence of an intact posterior capsule.

Secondary implantation of a posterior chamber intraocular lens in an aphakic eye devoid of an intact posterior capsule requires a special surgical approach. When lens capsule remnants remain in the periphery, the ciliary sulcus can be reconstructed to accommodate a posterior chamber lens. The fibrotic lens or capsular residues that often remain adherent to the posterior surface of the iris are divided with sharp intraocular scissors, and a shelf is created that is sufficient to support the lens haptics. A series of 28 cases, including 16 involving young children, demonstrates the feasibility and the favorable visual results obtainable with this surgical technique.

Adolescent↗

Mechanisms of platelet production.

The precise mechanism by which platelets are formed from megakaryocytes (MK) remains unclear, despite numerous studies which have been performed during this century. Models have been proposed that attempt to account for platelet formation from disruption of elongated processes of MK cytoplasm, designated proplatelets, or by fragmentation of MK cytoplasm. MK demarcation membranes are hypothesized by some investigators to delineate platelet territories in the MK cytoplasm, and by others to act as a membrane reservoir for MK process formation. Platelet production has been variously speculated to occur primarily in the bone marrow or lung. Each theory or model has attempted to elucidate the phenomenon of size heterogeneity of circulating platelets and the changes that occur under conditions of altered thrombopoiesis. In this article, we have analyzed and compared the characteristics of previously proposed models for platelet production and suggested additional techniques for future studies of thrombopoiesis.

Animals↗

A modified Limulus amebocyte lysate test with increased sensitivity for detection of bacterial endotoxin.

We have developed a simple modification of the chromogenic Limulus amebocyte lysate test that increases the sensitivity for the detection of bacterial endotoxins. In this assay, free paranitroaniline, cleaved from synthetic chromogenic substrates by proteases that were generated by Limulus lysate after incubation with endotoxin, was then derived. Derivation was with p-dimethylaminocinnamaldehyde in the presence of strong acid, forming a stable Schiff base end product with much greater molar absorbancy than the parent chromogen. Conditions (times and temperatures of incubations, concentrations of reagents) for the augmented chromogenic procedure were optimized. A ten-fold or greater increase in sensitivity for bacterial endotoxin was obtained with the modified assay as compared with the standard chromogenic Limulus test, with unequivocal detection of endotoxin concentrations of less than 100 pg/ml. The greater sensitivity of this modified Limulus test increases its usefulness for a wide range of research applications and clinical investigations.

Colorimetry↗

The effect of partially purified thrombopoietin on guinea pig megakaryocyte ploidy in vitro.

Enriched populations of guinea pig bone marrow megakaryocytes were prepared by density gradient and velocity centrifugation and maintained in liquid cultures for 24 or 48 h. The resulting megakaryocyte preparations were of 86.1% +/- 5.5% purity. After 24 or 48 h in liquid culture, recovery of viable cells was 77% +/- 11% or 83% +/- 13%, respectively. Megakaryocyte cultures were supplemented with 100-200 micrograms/ml of either a lectin-fractionated preparation of thrombopoietin (TPO) from the plasma of thrombocytopenic rabbits or an identically prepared protein fraction from non-thrombocytopenic animals. Addition of TPO resulted in a significant increase (p less than 0.05) in both the proportion and total numbers of 32N megakaryocytes and a significant decrease (p less than 0.05) in the relative frequency of 8N megakaryocytes. In most experiments, a decrease in the total number of 8N megakaryocytes also was noted. These results indicate that partially purified TPO is able to increase the ploidy (DNA levels) of megakaryocytes in vitro.

Animals↗

Intervention in detention. Psychological, ethical and professional aspects.

The psychological stressors in detention, besides being a frequent cause of distress, are also significant obstacles to effective intervention. Conditions for detention in South Africa, laid down by law, have been described as psychological torture. These legal conditions for detention conflict with the ethical principles of autonomy, non-maleficence and beneficence and by compromising ethical principles result in inadequate clinical standards. It is therefore not possible to provide an adequate mental health service for detainees. Attempts to formulate minimum standards for the psychological treatment of detainees do not address the problem that the conditions of indefinite detention are incompatible with providing mental health care services. Professional ethics are subverted by legalising unethical practice, and attempts to criminalise ethical practice should be resisted. It is important for the mental health professional to address these issues so as not to abrogate his responsibilities to himself, his patients, and his profession.

Dissent and Disputes↗

Comparison of absorption measurements of DNA stain content by utilizing video and scanning image cytometers.

After staining with the Feulgen reaction, the DNA stain contents of 155 mouse bone marrow cells and 22 adjacent chicken erythrocytes were measured by absorption image cytometry by utilizing two different systems--a scanning cytometer and a video cytometer. In the scanning cytometer (M85 microdensitometer, Vickers Instruments, Malden, MA), a spot of light was scanned across the cell. In the video cytometer (TAS Plus, E. Leitz, Rockleigh, NJ), the microscope field, which may contain several nuclei, was imaged onto a Plumbicon video camera. With each system, cells were scanned, digitized into their elementary pixels, and analyzed to determine their integrated absorbance. Comparison of the DNA stain contents of the same G0/G1 bone marrow cells and chicken erythrocytes, as measured by video and scanning cytometry, showed that both techniques gave comparable results; scanning cytometry is more precise. The coefficients of variation of the measurements for the G0/G1 bone marrow cells and for the chicken erythrocytes were 5.9% and 7.0%, respectively, when measured by video cytometry at the absorption peak (584 nm), compared to 4.1% and 3.5%, respectively, for the same cells when measured by scanning cytometry off the absorption peak (615 nm). The video-based measurements were relatively lower than the scanning measurements for darkly stained cells; this suggests that glare and other optical errors which increase with stain darkness caused greater systematic errors in the video cytometer than they did in the scanning cytometer.

Animals↗

Thrombocytopenia associated with repletion of iron in iron-deficiency anemia.

Two patients with iron deficiency experienced rapid decreases in their platelet levels following initiation of replacement therapy with oral ferrous sulfate or ferrous gluconate. The first patient, whose pretreatment platelet count was 168,000 per mm3, developed marked thrombocytopenia (platelet count, 21,000 per mm3) on the sixth day of iron repletion. The second patient's platelet level fell from 725,000 to 105,000 per mm3 on the tenth day of therapy. In both instances, platelet levels gradually returned to normal levels. The data suggest that the administration of oral iron resulted in an acute reduction in platelet production. The mechanism(s), prevalence, and clinical significance of thrombocytopenia following iron repletion in patients with iron deficiency anemia remain unknown.

Adolescent↗

Plasma cortisol and corticosteroid-binding globulin in essential hypertension.

Plasma concentration of cortisol, total CBG-binding capacity, and blood pressure were measured in control subjects (n = 171), patients with essential hypertension (EH; n = 210) and their first-degree normotensive (NR; n = 84) or hypertensive (HR; n = 66) relatives. Mean (+/- SD) plasma cortisol was significantly (p less than 0.001) decreased in EH (10.1 +/- 4.3 g/dl) patients and HR (11.7 +/- 4.1). Plasma cortisol in NR did not differ from control values (14.3 +/- 4.5) but the distribution of individual values covered the entire control-EH (14.6 +/- 5.5) range. Mean (+/- SD) CBG-binding capacity was significantly (p less than 0.001) lower in EH (14.4 +/- 3.0), NR (17.5 +/- 2), HR (17.6 +/- 2.2) as compared to controls (20.9 +/- 2.1), indicating that the decline in EH and in most relatives was mainly in plasma CBG-bound cortisol. The plasma CBG-binding capacity for cortisol was significantly negatively correlated with mean arterial pressure (MAP) in both controls (p less than 0.001) and NR (p less than 0.01) but not in either HR (r = 0.02) or never-treated EH patients. Total afternoon plasma aldosterone was higher (p less than 0.01 vs. controls) in 93 untreated EH patients (11.2 +/- 4.8 ng/dl) than in either 161 first-degree relatives (8.1 +/- 3.4 ng/dl) or 117 controls (7.6 +/- 3.5 ng/dl). The respective aldosterone-binding globulin (ABG) binding capacities for aldosterone were 21.2 +/- 6.7, 20.1 +/- 9.3 and 9.8 +/- 4.0%. In all these subjects taken together, there was a positive correlation between MAP and ABG-binding capacity (r = 51; p less than 0.001). The association of reduced plasma cortisol and decreased CBG binding capacity in EH may be closely related to altered steroid metabolism, which may be partly explained by an abnormality resembling a relative deficiency in adrenal 17 alpha- and 11 beta-hydroxylation. In some EH patients, hypertension may be the result of the ineffectiveness of plasma cortisol in preventing slightly elevated endogenous ACTH levels leading to an increase in ACTH-sensitive steroids.

Adolescent↗

Use of arabinogalactan to obtain washed murine platelets free of contaminating plasma proteins and appropriate for studies of function, morphology, and thrombopoiesis.

A simplified procedure for preparing washed murine platelets, free of contaminating plasma proteins, has been developed. Platelet-rich plasma (PRP) was prepared from diluted whole blood from C57BL/6N mice by two centrifugations at 100 x g for 12 minutes. Platelets were concentrated and then washed by centrifugation through isosmolar 10% arabinogalactan (Stractan). Platelet recovery was 85% +/- 6% (1 SD) (n = 10) from whole blood to PRP and 86% +/- 4% (1 SD) (n = 6) from PRP to Stractan-washed platelets. Overall recovery of platelets with this technique was 73% +/- 10% (1 SD). Contamination of platelets with plasma proteins could not be detected with use of unlabeled platelets that had been incubated with radiolabeled plasma proteins followed by washing with Stractan. The Stractan-washed platelets were assessed for function by using aggregometry. The response of Stractan-washed platelets to collagen and thrombin was identical to that of unwashed platelets. Stractan-washed platelets did not respond to 20 mumol/L adenosine diphosphate unless supplemented with 12% platelet-free plasma. The morphology of the Stractan-washed platelets indicated that degranulation had not occurred. With use of antibodies directed against the alpha granule membrane protein GMP-140 or fibrinogen, no evidence of secretion or plasma protein contamination was observed. The use of this method resulted in an improved assay for the rate of thrombopoiesis, based on detection of radioactive proteins in newly synthesized platelets, by eliminating contamination by radioactive plasma proteins. Our results indicate that this procedure is a convenient method for the separation of platelets from platelet-rich plasma, free of plasma proteins, which are suitable for bioassays, functional studies, and morphologic investigations.

Animals↗

Antidepressant binding to the porcine and human platelet serotonin transporters.

The ability of four antidepressant drugs, imipramine, alaproclate, norzimelidine, and fluvoxamine, to inhibit serotonin transport into platelet plasma membrane vesicles was tested over a range of external Na+ concentrations. Imipramine affinity, as we previously reported [J. Biol. Chem. 258:6115-6119 (1983)] increases sigmoidally with Na+. When measured by inhibition of serotonin transport, the affinity for alaproclate and norzimelidine is much less sensitive to Na+ and fluvoxamine actually inhibits more avidly at lower Na+. All of the drugs competitively inhibit serotonin transport. Moreover, alaproclate, norzimelidine, and fluvoxamine all competitively displace [3H]imipramine from platelet plasma membranes. The Ki for fluvoxamine inhibition of transport is 16-fold higher than its Ki for inhibition of imipramine binding. In contrast, alaproclate inhibits transport at concentrations lower than those required to block imipramine binding. In the case of fluvoxamine, and possibly also alaproclate, these differences are not due to separate sites mediating substrate and imipramine binding but rather to differences in the nature of binding and transport measurements. The results suggest that these antidepressant drugs and serotonin all bind to the same site, or to overlapping sites on the serotonin transporter, or to sites on the transporter whose occupation is mutually exclusive with substrate site occupation. The observation that binding of each ligand reacts differently to changes in Na+ suggests that distinct subsites are involved in each case. As reported previously by Wennogle and Myerson [Eur. J. Pharmacol. 86:303-307 (1983)] serotonin decreases the rate of imipramine dissociation from human platelet membranes. This effect is not observed in porcine platelets, is not Na+ dependent, and requires serotonin concentrations over 100 times the Km for transport. It is likely, therefore, to result from serotonin binding to a site distinct from the transport active site.

Animals↗