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Biomedical subjects

A Katz

Publications and source records attributed to A Katz.

At least 163 records · Page 9Linked to original sources
PubMed1996

Aspergillosis in systemic lupus erythematosus.

Infection is the major cause of morbidity and mortality in systemic lupus erythematosus (SLE). Although various fungi account for a substantial number of these lethal infections, aspergillosis, an important opportunistic infection in immunosuppressed patients, is described rarely. Only 23 cases have been reported in the English-language medical literature. Risk factors for acquiring aspergillosis in these patients were high grade disease activity, granulocytopenia, use of steroids and other immunosuppressive treatment and presence of bacterial infection. The diagnosis in most patients was delayed and they died. Here, we describe three SLE patients with invasive aspergillosis. Features of our patients' diseases were similar to those reported previously. Aspergillosis appeared while they had active SLE treated with high dose corticosteroids. In 2 patients the fungal infection was systemic and diagnosed post mortem. Both were leukopenic and had concurrent bacterial infection and one received amphotericin B prior to death. In the third, the infection was localized to a transplanted kidney and was cured by nephrectomy. Aspergillosis should be suspected in patients with active SLE, who are immunocompromised and sustain concomitant bacterial infections. The currently poor prognosis may be improved with more aggressive diagnostic investigation and treatment.

Adolescent↗
PubMed1996

Mutations in a C. elegans Gqalpha gene disrupt movement, egg laying, and viability.

We find that C. elegans egl-30 encodes a heterotrimeric G protein a subunit more than 80% identical to mammalian Gqalpha family proteins, and which can function as a Gqalpha subunit in COS-7 cells. We have identified new egl-30 alleles in a selection for genes involved in the C. elegans acetylcholine response. Two egl-30 alleles specify premature termination of Gqalpha and are essentially lethal in homozygotes. Animals homozygous for six other egl-30 alleles are viable and fertile, but exhibit delayed egg laying and leave flattened tracks. Overexpression of the wild-type egl-30 gene produces the opposite behavior. Analysis of these mutants suggest that their phenotypes reflect defects in the muscle or neuromuscular junction.

Amino Acid Sequence↗
PubMed1996

No change in insulin mediators in human skeletal muscle during isometric contraction or recovery.

The rapid activation of glycogen synthase in human skeletal muscle during recovery from isometric contraction is dependent on an intact circulation, which suggests the requirement of an activating humoral factor. To determine whether the activating factor is insulin, muscle biopsies were obtained from subjects at rest, at fatigue, 3 min postexercise with an intact circulation, and 3 min postexercise during which circulation to the muscle was occluded. Two inositol phosphoglycan mediators of insulin action were isolated from the biopsies, and bioactivity was measured by determining the effects of the isolated mediators on the activities of purified cyclic AMP-dependent protein kinase, pyruvate dehydrogenase phosphatase and glycogen synthase phosphatase in vitro. Bioactivity was not altered by any condition compared with rest. These data suggest that changes in inositol phosphoglycans are not responsible for the circulation-dependent activation of glycogen synthase during recovery from exercise.

Adult↗
PubMed1996

Successful treatment of progressive outer retinal necrosis syndrome.

PURPOSE: Progressive outer retinal necrosis is a destructive retinopathy found in patients with acquired immune deficiency syndrome. Treatment of this disorder has been unsuccessful in reported patient series, with the patients experiencing profound bilateral loss of vision. METHODS: We treated six patients with combination antiviral therapy, usually with intravenous foscarnet and either ganciclovir or acyclovir. RESULTS: These six patients retained a visual acuity of 20/100 or better in at least one eye for the remainder of their lives (a period > 4 months for each patient). Retinal detachments developed in four patients, for which vitrectomy and silicone oil tamponade were required. CONCLUSIONS: A combination of intravenous antiviral therapy and aggressive vitrectomy techniques to repair any associated detachments may allow the preservation of useful visual acuity in patients with progressive outer retinal necrosis. This is the first reported series of successful long-term treatment of patients with this disorder.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Single lead VDD pacing: multicenter study.

Optimal treatment for patients with AV block and normal sinoatrial node (SA) function entails atrial sensing and ventricular pacing (VDD mode). Single-lead VDD pacing preserves AV synchrony, precludes the need to insert two leads, and makes the implanter's work simpler and quicker. Our objectives were to verify the performance of the Thera VDD pacing system (medtronic, Inc., Minneapolis, MN, USA), and evaluate the effectiveness of its atrial sensing and its ventricular sensing and pacing. In 165 patients, 150 adults (mean age 62 +/- 18 years) and 15 children (mean age 7 +/- 5 years) with 1 degree-3 degrees AV block and normal SA node function, a Thera VDD system (Models 8948 or 8968) was implanted. Intraoperative ventricular electrical measurements were not significantly different from those of VVI pacemakers. The mean amplitude of the atrial signal during implantation was 4.1 +/- 1.9 mV. Optimal atrial signals during implantation were usually obtained in the mid or lower part of the right atrium by using a special technique. Adequate atrial measurements remained stable throughout 24 months. There was no difference between serial measurements of atrial signal amplitudes at predischarge and during follow-up visits. Reposition of the lead was done in 2 patients (1.4%), and reprogramming to VVI in 7 patients: due to atrial fibrillation in 3 (1.8%) and due to atrial undersensing in 4 patients (2.4%). Thera VDD pacing is reliable and easy to manage with dependable atrial sensing and ventricular pacing. The survival rate of VDD pacing at 2 years was 96%.

Adolescent↗
PubMed1996

Intact glucose transport in morphologically altered denervated skeletal muscle from quadriplegic patients.

The present study was undertaken to investigate the nature of the whole body insulin resistance that characterizes patients with complete cervical spinal cord lesion. Nine patients with C5-C7 lesions and ten age-matched healthy individuals were studied. Whole body insulin-mediated glucose utilization was reduced by 43% in the quadriplegic patients compared with the controls (P < 0.001). In the quadriplegic patients, lean body mass corresponded to 66 +/- 3% of total body mass. Despite whole body insulin resistance, in isolated vastus lateralis muscle, basal and insulin-stimulated 3-O-methylglucose transport, as well as protein expression of the insulin or exercise-regulatable glucose transporter, GLUT-4, and glycogen content were comparable between the patients and controls. Strikingly, muscle fiber area was reduced by 44% (P < 0.05), percentage of type IIb fibers was increased (P < 0.01), and there was a complete loss of type I fibers in the patients. In conclusion, the dissociation between whole body insulin-mediated glucose uptake and skeletal muscle glucose transport in quadriplegic patients primarily reflects the decreased muscle mass. Furthermore, these findings demonstrate a remarkable capacity of skeletal muscle to maintain an intact glucose transport system despite severe morphological alterations.

Adult↗
PubMed1996

The role of public policy in health care market change.

Market forces appear dominant in the transformation of health care systems across the United States. However, in many markets public policy remains an important factor--guiding, facilitating, and in some cases prompting change. This paper reviews how the debate over health care reform acted as a catalyst in local health care financing and delivery systems, and how other public policy tools are affecting the fifteen markets studied in the Community Snapshots project. We then discuss prospects for public policy in the near term and the longer term, using two scenarios to illustrate possible future roles.

Community Health Planning↗
PubMed1996

Cryocrystalglobulinemia mimicking rheumatoid arthritis and vasculitis.

We describe a patient with longstanding arthropathy resembling rheumatoid arthritis (RA) and cold induced purpura for many years, concomitant with IgG kappa paraproteinemia. At autopsy, the patient was found to have evidence of widespread vascular occlusions due to precipitated crystals as well as tissue deposition of crystals. Neither vasculitis nor synovitis was observed despite the clinical picture of both. Blood and synovial fluid obtained antemortem were found to spontaneously form crystals when stored at 4 degrees C, and the washed crystals were composed of the same monoclonal IgG kappa previously found in serum. Cryocrystal formation occurred at 33 degrees C and neutral pH. This patient thus had cryocrystalglobulinemia mimicking clinical manifestations of RA and vasculitis.

Arthritis, Rheumatoid↗
PubMed1996

Felodipine in the treatment of severe refractory hypertension.

The efficacy of felodipine and tolerance of this drug was examined in 52 patients, 23 men and 29 women, 18-76 years of age, in whom it either replaced previous therapies of nifedipine and other vasodilators, or was added to a constant dose of beta blockers and diuretics or another previous therapy, which was unchanged. Felodipine significantly reduced blood pressure (BP), from 192.3 +/- 31.9/114.3 +/- 18.0 to 155.7 +/- 19.5/93.8 +/- 11.5 mm Hg, with no change in pulse rate. There were no significant biochemical changes, renal deterioration or blood sugar disequilibrium. Adverse reactions including flushes and leg edema could be tolerated by most of the patients, however six patients dropped out. Orthostasis dictated a decrease in felodipine dosage. Felodipine appears to be a highly potent, well tolerated drug and offers a substitute treatment for severe hypertensives refractory to other vasodilators.

Adolescent↗
PubMed1996

[Indapamide--a substitute diuretic for hypertensives with hyperglycemia and/or dyslipidemia].

Diuretics are among the first drugs offered to the hypertensive patient. However, they can induce metabolic changes resulting in cardiovascular insult. Especially noteworthy are increased levels of glucose and lipids. Indapamide is a diuretic and vasodilator that does not raise blood glucose or lipid levels. We therefore investigated its use as a substitute diuretic in patients whose treatment had resulted in hyperglycemia and/or hyperlipidemia. In 24 hypertensives, Indapamide, 2.5 mg daily, replaced the diuretic therapy they were receiving. Blood pressure, blood glucose, hemoglobin A1C and lipid profile were measured before and every month during the 6 months of Indapamide treatment. Replacement of diuretics with Indapamide significantly reduced blood glucose from 148 +/- 53 mg/dl to 127 +/- 37, p = 0.05 HbA1C from 8.42 +/- 0.4 mg/dl to 7.7 +/- 2.0, p = 0.05; total cholesterol from 253 +/- 45 mg/dl to 228 +/- 43, p < 0.05; and triglycerides from 224 +/- 145 mg/dl to 176 +/- 91, p < 0.05. Blood pressure was better controlled with Indapamide than with previous medications. It was reduced from an average of 155 +/- 1 systolic and 89 +/- 8 diastolic (mm Hg), to 142 +/- 13 and 83 +/- 7, respectively, p < 0.05. We conclude that Indapamide is safe and effective in lowering blood pressure and contributes to better control of blood glucose and lipid levels in diabetic and dyslipidemic patients, compared to standard diuretics.

Antihypertensive Agents↗
PubMed1996

Merkel cell carcinoma in Israel.

Merkel cell carcinoma is a rare and highly malignant skin tumor. We present the first report on the clinical and epidemiologic characteristics of Merkel cell carcinoma in Israel. Our findings, including average age of 69 years at diagnosis, equal sex distribution, disease location on sun-exposed skin, and an overall 3 year survival of 58%, are consistent with the data reported in the literature. Unique findings in our study were the predominance of Ashkenazic Jews and the excessive rate of second malignancies. This initial report on Merkel cell carcinoma in Israel emphasizes the need for increased awareness of this aggressive and potentially lethal skin malignancy.

Adult↗
PubMed1995

Characterization of hematopoietic progenitors from human yolk sacs and embryos.

Hematopoiesis first arises in the extraembryonic yolk sac, and it is generally believed that yolk sac-derived stem cells migrate and seed the fetal liver at approximately week 6 of development in humans. Recently, the identification at day 8.5 to 9 of multipotential stem cells in intraembryonic sites different from the liver suggests that the establishment of hematopoiesis might be more complex than initially believed. In an attempt to understand initial steps of hematopoiesis during human ontogeny, we characterized clonogenic myeloid progenitor cells in human yolk sacs and corresponding embryos at 25 to 50 days of development. Most erythroid colonies derived from the yolk sacs differed from adult marrow-derived progenitors in that they also contained cells of the granulomacrophagic lineage, suggesting that they were pluripotent and exhibited a different response to cytokines. Furthermore, a subclass of nonerythroid progenitors generated very large granulomacrophagic colonies, some of which generated secondary erythroid colonies on replating. Analysis of the distribution of progenitors revealed that in contrast to erythroid progenitors, whose numbers were equally distributed between the yolk sac and the embryo, 80% of the nonerythroid progenitors were found in the embryo at stages II and III. Interestingly, a high proportion of nonerythroid progenitors (including high proliferative potential cells) was present in colony assays initiated with cells remaining after the liver has been removed. These findings were validated in colony assays established with CD34+ cells purified from extraembryonic yolk sacs and intraembryonic tissues. Increased knowledge about the biology of hematopoietic stem cells early in life may help to further understanding of the mechanisms associated with the restriction in proliferative and differentiative potential observed in the adult hematopoietic stem cell compartment.

Adult↗
PubMed1995

Effects of CGS 9343B (a putative calmodulin antagonist) on isolated skeletal muscle. Dissociation of signaling pathways for insulin-mediated activation of glycogen synthase and hexose transport.

The role of calmoudulin in control of carbohydrate metabolism in the absence and presence of insulin in isolated mouse soleus muscle was investigated. The calmodulin antagonist CGS 9343B had no effect on basal glycogen synthase activity, the contents of high energy phosphates, glucose-6-P, or glycogen synthesis. However, CGS 9343B inhibited the basal rates of 2-deoxyglucose uptake and 3-O-methylglucose transport by 30% (p < 0.05) and 40% (p < 0.001), respectively. Insulin activated glycogen synthase by almost 40% (p < 0.01) and this increase was not altered in the presence of CGS 9343B. Insulin increased the muscle content of glucose-6-P (approximately equal to 2-fold), as well as glycogen synthesis (approximately equal to 8-fold), 2-deoxyglucose uptake (approximately equal to 3-fold), and 3-O-methylglucose transport (approximately equal to 2-fold), and these increases were inhibited by CGS 9343B. In additional experiments on isolated rat epitrochlearis muscle, it was found that the hypoxia-mediated activation of 3-O-methylglucose transport was also inhibited by CGS 9343B. These data demonstrate that: 1) hexose transport, both in the absence and presence of external stimuli (insulin and hypoxia), requires functional calmodulin; and 2) insulin-mediated activation of glycogen synthase does not require functional calmodulin, nor can it be accounted for by increases in glucose transport or glucose-6-P.

3-O-Methylglucose↗
PubMed1995

The Mpl-ligand or thrombopoietin or megakaryocyte growth and differentiative factor has both direct proliferative and differentiative activities on human megakaryocyte progenitors.

Previously, it was believed that megakaryocytopoiesis was regulated by two types of humoral factors: megakaryocyte colony-stimulating factor (MK-CSF), which acts on progenitors inducing their proliferation, and thrombopoietin (TPO), a megakaryocyte(s) (MK) maturational factor that induces platelet formation. The recently cloned Mpl-ligand (Mpl-L) seems to have both properties in vivo and in vitro and has also been called TPO. However, it cannot be excluded that a part of these activities is due to a synergistic effect with growth factors present in the serum or synthesized by accessory cells. To delineate the precise TPO (Mpl-L) biologic activities, we performed serum-free cultures at limiting cell dilution. Target cells were adult human marrow CD34+CD41+ cells, which represent a highly selected population of late MK progenitor or transitional cells. Cells were purified using a flow cytometer equipped with an automatic cloning design unit. We determined that the recombinant molecule had a biologic activity that reached a plateau at 10 ng/mL. At this concentration, a linear relationship between the average MK number per well and the number of cells seeded (between 1 to 50 cells per well) was observed. At one cell per well, 60% of the wells contained a single MK at day 5 of culture. Half of these wells contained only one large MK, whereas the other half contained several MK (up to 25), demonstrating that TPO has direct proliferative biologic activity. In contrast, at limiting dilution, none of the other cytokines tested (stem cell factor [SCF], interleukin-6 [IL-6], and erythropoietin [Epo]) were effective, whereas IL-3 showed a mild effect. However, a combination of SCF plus IL-6 plus IL-3 produced similar results as TPO alone. Addition of the other cytokines to TPO did not enhance the cloning efficiency of the CD34+CD41+ cells but increased twofold the average number of MKs per clone. MKs reached a ploidy of 32N and 64N in the presence of TPO. The mean ploidy value was approximately 6 and was not modified by addition of the other cytokines. At the ultrastructural level, a majority of the MKs showed maturational defects related to an imbalance between the synthesis of alpha-granules and demarcation membranes. However, a fraction (about 30%) had a cytoplasmic maturation that exactly mimicked that of marrow MKs. In addition, proplatelet-shedding MKs were observed in the cultures, even at limiting dilution. Such a result was not observed with any other individual cytokines, including the combination of three cytokines.(ABSTRACT TRUNCATED AT 400 WORDS)

Antigens, CD↗