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Biomedical subjects

J Levine

Publications and source records attributed to J Levine.

At least 19 recordsLinked to original sources

Clinical predictors of relapse following neuroleptic withdrawal.

The validity of previously hypothesized predictors of elapse following neuroleptic discontinuation was examined. One hundred sixty-two outpatients, with either Research Diagnostic Criteria schizophrenia or schizoaffective disorder, were discontinued from neuroleptic medication for a 28-day period or until judged to be relapsed. Pre-discontinuation neuroleptic dosage level, the severity of psychotic symptoms, and the presence of dyskinetic movements prior to neuroleptic discontinuation were the predictor variables. Of the 162 patients, 62.7% did not relapse during the study period. There were no differences in the survival rates between the patients withdrawn from oral versus depot neuroleptics. Neuroleptic dosage, but not severity of psychotic symptoms or dyskinetic movements, predicted relapse. These results support the hypothesis that pre-withdrawal neuroleptic dosage level predicts relapse, but fail to validate either severity of psychotic symptoms or presence of dyskinetic movements as predictors of relapse.

Administration, Oral

Efficacy and risks of moricizine in inducible sustained ventricular tachycardia.

OBJECTIVE: To assess the efficacy and toxicity of moricizine in treating patients with serious ventricular arrhythmias and inducible sustained ventricular tachycardia. DESIGN: Uncontrolled clinical trial. SETTING: The intensive care and telemetry units of Northwestern Memorial Hospital, St. Francis Hospital and Medical Center, and Lenox Hill Hospital. PATIENTS: Twenty-six patients with sustained ventricular arrhythmias or hemodynamically significant nonsustained ventricular tachycardia, most of whom failed therapy with at least one class I antiarrhythmic agent. INTERVENTION: Patients were treated with moricizine, 400 to 1000 mg/d. MEASUREMENT: Efficacy was assessed by the results of programmed ventricular stimulation done during moricizine therapy. MAIN RESULTS: Seven of the 26 patients (27%) developed life-threatening ventricular proarrhythmia during moricizine loading. Three patients had incessant sustained ventricular tachycardia, two had incessant nonsustained ventricular tachycardia, one had new sustained ventricular tachycardia, and one had new cardiac arrest. One of these patients died of intractable ventricular fibrillation. No clinical or electrophysiologic variables clearly identified those at risk for proarrhythmia. Only 3 of 26 patients (12%) became noninducible on moricizine. CONCLUSION: Moricizine has a low rate of efficacy and carries a considerable risk for life-threatening proarrhythmia in patients with serious ventricular arrhythmias and inducible ventricular tachycardia who have failed therapy with other class I antiarrhythmic agents.

Adult

The UAS(MAL) is a bidirectional promotor element required for the expression of both the MAL61 and MAL62 genes of the Saccharomyces MAL6 locus.

Maltose fermentation in Saccharomyces yeasts requires one of five unlinked MAL loci: MAL1, 2, 3, 4, or 6. Each locus consists of three genes encoding maltose permease, maltase and the MAL activator. At MAL6 the genes are called MAL61, MAL62 and MAL63, respectively. Transcription of MAL61 and MAL62 is coordinately induced by maltose and repressed by glucose and this regulation is mediated by the MAL activator. By deletion analysis of the MAL61-MAL62 intergenic region, we show that a 68-basepair region, from base pairs -515 to -582 upstream of the MAL61 start codon, contains a sequence necessary for the maltose-induced expression of MAL61 and MAL62, the UAS(MAL). This sequence contains two copies of an 11-basepair dyad which may be the active elements of the UAS(MAL). Using heterologous gene plasmid constructs, we demonstrate that the UAS(MAL) sequence is sufficient for maltose inducibility of MAL62 and that this regulated expression requires a functional MAL activator. Our results suggest that the MAL61-MAL62 intergenic region contains additional distinct elements which function to precisely regulate MAL61 and/or MAL62 expression. Among these are repressing sequences, including a glucose-responsive element located between base pairs -583 and -638, which is partially responsible for mediating glucose-repression of MAL62 expression.

Base Sequence

Acute jejunoileitis. A distinct entity?

A 44-year-old man with acute jejunoileitis of unknown etiology developed small bowel obstruction. Intermittent abdominal pain, bloody diarrhea, ascites, and leukocytosis were prominent features. All stool cultures were negative. On steroid treatment, symptoms and radiographic features completely resolved. We suggest, in agreement with an earlier report, that acute jejunoileitis may be regarded as a distinct clinical entity.

Adult

Exogenous factors in Crohn's disease. A critical review.

The etiology of Crohn's disease remains elusive. Though there may be a genetic predisposition to the disease, epidemiologic evidence suggests that environmental factors are important. The role of dietary components and enhanced intestinal permeability deserve more attention. From this review of past studies, this investigator believes that ingested compounds may play an important role in the pathogenesis of Crohn's disease. Silica and various silicates provide models of how dietary factors might cause the disease and explain some of its features.

Cell Membrane Permeability

Profound persistent eosinophilia in a patient with spontaneous renal atheroembolic disease.

We describe an elderly women who died of renal failure secondary to spontaneous renal atheroembolic disease. The sole clinical clue to this diagnosis was a profound eosinophilia up to 19,100/mm3 and a relative eosinophil count of 80%. Renal atheroembolic disease should be a prominent consideration in any patient with both renal insufficiency and peripheral eosinophilia.

Aged

Epidermal growth factor receptors in idiopathic and virally induced skin diseases.

The altered distribution of epidermal growth factor receptors (EGF-R) in hyperproliferative skin lesions such as psoriasis vulgaris, seborrheic keratoses, acanthosis nigricans, ichthyosis, and others implies aberrant control of growth/proliferation by epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and other growth factors/cytokines. Whether overexpression of EGF-R: 1) correlates with epidermal proliferation, 2) serves as a hallmark of specific dermatoses, or 3) is due to modulation by multiple growth factors remains unclear. To correlate distributions of EGF-R with in vivo proliferative status, two benign diseases of unknown etiology, seborrheic keratoses and acrochordons (skin tags), were examined using EGF-R immunolocalization and 125I-EGF binding techniques. Lesions documented as growing by clinical criteria or 5-bromodeoxyuridine incorporation (a measure of cell proliferation) were compared to nongrowing lesions of the same type. To correlate distributions of EGF-R to specific dermatoses, skin diseases of viral etiology (verruca vulgaris and molluscum contagiosum) were also probed by EGF-R immunolocalization and 125I-EGF binding. Elevated immunostaining for EGF-R and 125I-EGF binding sites were associated with actively growing seborrheic keratoses and skin tags whereas normal patterns of immunostaining and 125I-EGF binding were seen in nongrowing seborrheic keratoses and skin tags. Viral diseases showed unique patterns. No EGF-R were detected in verruca vulgaris. Molluscum contagiosum lesions showed intense EGF-R in basal keratinocytes and no EGF-R in virally infected cells. Thus elevations in EGF-R show a positive in vivo correlation with proliferation in at least two differing benign diseases of the epidermis. The decreased levels of EGF-R in virally infected lesions suggests that EGF-R may show unique patterns for specific dermatoses and are not universally elevated in benign hyperproliferative skin disorders.

Cell Division

Imbalanced cytokine production by macrophages from autoimmune-prone mice.

Peritoneal macrophages from multiple autoimmune-prone strains of mice (MRL/lpr, MRL/+, NZB/W, BXSB, and B6/gld) show defective expression of the cytokines IL-1 and IL-6. Autoimmune mice were all used between 1 and 6 weeks of age, the earliest times being well before the onset of overt disease. Northern blot analysis reveals a parallel reduction in the levels of IL-1 alpha, IL-1 beta, and IL-6 mRNA. In contrast, the production of other proteins, including the cytokine TNF-alpha, appears to be normal. These findings imply an imbalance within the cytokine network of autoimmune macrophages. Studies on bone marrow-derived macrophage precursors, as well as macrophages from chimeric mice, suggest an intrinsic macrophage defect as opposed to conditioning by the autoimmune environment. This defect appears to be constant throughout the lifespan of autoimmune MRL/lpr mice, being equally apparent in 1-week old mice as in fully diseased 6-12-month-old mice. Aberrant regulation of IL-1 and IL-6 represents a novel defect in the function of autoimmune macrophages that is both intrinsic and substantial, and has the potential to contribute to the immune dysregulation that characterizes autoimmunity.

Animals

Family counseling and legal issues in Alzheimer's disease.

Caring for a patient with Alzheimer's disease produces significant stress and morbidity in the caregiver. This article reviews the existing evidence on caregiver burden in Alzheimer's disease and elaborates on the counseling and legal options that can be exercised by them. By availing of existing supports and planning ahead, caregivers can decrease burden levels and deliver more effective care to the patient.

Alzheimer Disease

Aberrant regulation of IL-1 expression in macrophages from young autoimmune-prone mice.

IL-1 is a multifunctional, immunoregulatory polypeptide produced by many cell types. Because activated macrophages are a major source of IL-1 and have also been implicated in the pathogenesis of autoimmune disease, we investigated the regulation of IL-1 expression in several autoimmune-prone strains of mice. Peritoneal macrophages derived from the autoimmune-prone strains MRL/lpr, MRL/+, NZB, and NZB/W F1, as well as NZW, displayed transient expression of IL-1 in contrast to the stable expression characteristic of control normal strains including A. Thy, A/J, B10, B10.A, B10.D2, C57BL/6, BALB/c, and C3H/HeN. The down-regulation of IL-1 by macrophages from the autoimmune-prone mice was not attributable to inherently defective signal transduction because macrophages from both the normal and autoimmune-prone strains displayed substantial initial levels of cell-associated and secreted IL-1. However, during the first 2 to 3 days in culture, macrophages from autoimmune-prone mice became progressively refractory to both induction and maintenance of IL-1, a pattern that correlated with changes in the levels of IL-1 alpha and beta mRNA. The progressive reduction in IL-1 expression by macrophages from these autoimmune-prone strains was not due to a reduction in general metabolism or viability, because expression of cell surface antigens, including MHC class I and II Ag and LFA-1, was comparable to that of control macrophages. Because IL-1 plays a critical role in the homeostasis of a variety of cell lineages, defective expression, and maintenance of IL-1 (and perhaps other cytokines) by macrophages from the autoimmune-prone strains may contribute to the immune dysregulation that develops in these mice. Alternatively, cytokine dysregulation might not contribute directly to disease, but rather reflect a more basic defect related to specific signal transducing or gene regulatory pathways.

Animals

Small-intestinal brushing cytology in the diagnosis of cryptosporidiosis in AIDS.

We report the cytologic findings of small intestinal brushing material showing cryptosporidiosis in two patients with acquired immunodeficiency syndrome (AIDS). Cryptosporidia measuring approximately 2-4 mu were aligned along the surface of the glandular cells, although many freely dispersed organisms were also present. The differential diagnoses of other structures that could be confused with cryptosporidia are also presented in this article. Small-intestinal brushing cytology may complement endoscopic biopsy in the workup of diarrheal diseases in AIDS, especially in patients with thrombocytopenia, since the bleeding disorder may be a contraindication for endoscopic biopsy.

Acquired Immunodeficiency Syndrome

Comparison of assays for prostatic and total acid phosphatase.

Total and tartrate inhibited acid phosphatase was determined on the Technicon Chem 1 and evaluated against a Cobas-Bio centrifugal analysis procedure and an immunochemical method. Precision and reference range studies were performed for the Chem 1 acid phosphatase procedure and correlation was established with the other methods. The Chem 1 method for measuring total and prostatic acid phosphatase is a sensitive method with good correlation to the centrifugal analysis and the immunochemical method. The assay is fully automated and requires no manual off-line sample preparation.

Acid Phosphatase

The role of urea kinetic modeling, TACurea, and Kt/V in achieving optimal dialysis: a critical reappraisal.

The National Cooperative Dialysis Study (NCDS) established the importance of the time-averaged concentration of blood urea nitrogen (BUN) (TACurea) as a determinant of morbidity among patients maintained on hemodialysis. Although urea is not itself toxic, it serves as a surrogate for those low-molecular weight products of protein catabolism that do contribute to uremic toxicity. The NCDS also reported an association between low protein catabolic rates (a measure of dietary protein intake) and increased morbidity, but the validity of this result has been questioned. On the basis of a retrospective re-analysis of the data, Gotch and Sargent have proposed following the normalized whole-body urea clearance, Kt/V, as a more fundamental index of the level of dialytic therapy. In this review, a comparison is made between these two measures of adequate dialysis, namely, midweek predialysis urea concentration and Kt/V. At least for the cellulosic membranes used in the NCDS, they seem to be equivalent. Furthermore, each prescription defines adequate nutrition as a dietary protein intake (DPI) of 1.0 g/kg/d. At this DPI, a time-averaged concentration of BUN of 17.9 mmol/L (50 mg/dL) (corresponding roughly to a midweek predialysis BUN of 21.4 to 28.6 mmol/L (60 to 80 mg/dL), as recommended by the NCDS, is equivalent to a Kt/V of 1.0, as recommended by Gotch and Sargent. Based on ease and accuracy of measurement, TACurea would seem the more reliable marker for monitoring the adequacy of dialysis. Extrapolation of the utility of TACurea and/or Kt/V to noncellulosic membranes remains to be established. Urea kinetic modeling constitutes a powerful mathematical tool for implementing these recommendations. Urea kinetic modeling may also be used as a means of monitoring DPI and thereby ensuring adequate nutrition.

Blood Urea Nitrogen

Continuous versus targeted medication in schizophrenic outpatients: outcome results.

The authors report on the outcome of treatment of 116 outpatients with chronic schizophrenia who were assigned to a 2-year, single-blind course of treatment with either targeted or continuous medication. These patients were not restricted to those who were good candidates for a medication reduction strategy. Continuous medication was superior to targeted medication in preventing decompensations and hospitalizations and in extent of employment at 2 years. Other measures of psychopathology and functioning at 1 and 2 years did not differentiate the two groups of patients. The targeted approach achieved a substantial reduction in total medication through a reduction in the number of days of medication administration.

Adult

The roles of social work in psycho-biological research.

Social Workers have an opportunity to utilize their skills in the arena of psychiatric research. Traditional areas of social work functions, including working with patients, families, groups, complicated systems, and interdisciplinary teams, as advocate, therapist, mediator, and manager, are all necessary for the successful implementation of psychiatric research projects with human subjects. The repertoire of social work skills can enhance the successful operation of research involving bio-psycho-pharmacological or neurobiological trials.

Brain