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Biomedical subjects

Michael David

Publications and source records attributed to Michael David.

48 records · Page 3Linked to original sources
PubMed2003

Prevalence and characterization of uremic pruritus in patients undergoing hemodialysis: uremic pruritus is still a major problem for patients with end-stage renal disease.

BACKGROUND: Pruritus is a common disabling problem in patients with advanced end-stage renal disease. Few studies have evaluated the clinical characteristics of uremic itch. OBJECTIVES: The aim of this multicenter study was to provide a comprehensive description of the prevalence and clinical characteristics of pruritus affecting patients with end-stage renal disease who are undergoing hemodialysis. METHODS: A detailed questionnaire recently developed was used to evaluate pruritus in 219 patients undergoing hemodialysis treatment in 3 dialysis units. We examined the relationship of the quality of dialysis and various factors and medical parameters to itch. RESULTS: Pruritus was a common symptom in the study population. Approximately 66% of the patients had pruritus at some point, and 48% were affected by it at the time of the study. There was no correlation between the occurrence of pruritus and demographic or medical parameters (type of kidney disease, medical management, dialysis efficacy as expressed by Kt/V) of the patient. The data suggest that uremic pruritus tends to be prolonged, frequent, and intense, and it can impair the patient's quality of life including a negative effect on sleep and mood. Major factors found to exacerbate pruritus include rest, heat, dry skin, and sweat. Major factors found to reduce pruritus include activity, sleep, hot and cold shower, and cold. Treatment with angiotensin inhibitors seemed to be more common among those with uremia who had itch (P =.02) whereas furosemide was more commonly used among those who never itched (P =.002). CONCLUSION: This study provides a detailed description of uremic pruritus with new data on its characteristics including affective and sensory dimensions and associated symptoms.

Adult↗
PubMed2003

Differences and similarities among expert opinions on the diagnosis and treatment of pemphigus vulgaris.

BACKGROUND: As a result of a lack of large-scale controlled studies, the diagnosis and management of pemphigus vulgaris (PV) has been solely on the basis of expert opinion, rather than on empirical evidence. We have completed a survey of worldwide experts on the diagnostic and therapeutic approaches to PV. METHODS: We conducted a telephone-based survey of 24 physicians from academic, tertiary care centers worldwide with an average of 20 years experience treating pemphigus. Survey questions included referral patterns, diagnostic techniques, and therapeutic regimens. RESULTS: Of those surveyed, 50% receive referrals within 6 months after onset of symptoms, 17% within 1 year, and 8% within 3 years. Diagnosis is secured by 96% using skin biopsy specimen with direct immunofluorescence, and by indirect immunofluorescence alone for 4%. None of the participating physicians make the diagnosis of PV solely on clinical and histologic evidence. Of the physicians, 75% initially treat with prednisone and 25% use other agents or attempt to eliminate potential triggers. The physicians who initially used noncorticosteroid drugs did so with no relation to the nature or extent of the disease. Of those surveyed, 50% use prednisone doses of 1 mg/kg/d, 31% use 1 to 1.5 mg/kg/d, and 19% use 1.5 to 3 mg/kg/d. Azathioprine is used as an adjuvant by 44%, mycophenolate mofetil by 20%, cyclophosphamide by 16%, and methotrexate by 8%. Complete discontinuation of prednisone was the goal for 37% whereas others were satisfied with doses from 2.5 to 10 mg/d. CONCLUSION: Wide variation exists in diagnostic techniques and treatment of PV, even among the world's experts. The lag time from symptom onset to referral emphasizes the need for heightened awareness. There is clearly a need for consensus standards with regard to patient stratification and randomized controlled trials.

Azathioprine↗
PubMed2003

Climatotherapy at the Dead Sea is a remittive therapy for psoriasis: combined effects on epidermal and immunologic activation.

BACKGROUND: The beneficial effect of climatotherapy at the Dead Sea (CDS) for psoriasis has been established clinically but there is a striking lack of studies assessing its in vivo effect at the molecular and cellular levels. OBJECTIVE: We sought to study the response of activated immunologic cells and keratinocytes in psoriatic lesions to CDS. METHODS: A total of 27 patients with chronic, stable, plaque-type psoriasis treated with CDS for 28 consecutive days were evaluated with the Psoriasis Area and Severity Index score and quantitative histologic measures. RESULTS: After 4 weeks of treatment, the overall Psoriasis Area and Severity Index score decreased by 81.5%. Complete clearance was achieved in 48% of the patients, and moderate to marked improvement in 41%. The average duration of remission was 3.3 months. Histologically, there was an overall reduction in malpighian layer thickness by 63.4%, and keratinocyte hyperplasia, assessed by Ki-67 cell cycle antigen expression, decreased by 78%; residual cell proliferation was confined mainly to the basal layer. These changes were accompanied by normalization of keratin 16 expression in 90% of the patients. T lymphocytes were almost totally eliminated from the epidermis (depletion of >90% of CD3(+) and CD25(+) cells), with only a low number remaining in the dermis (depletion of 69.4% of CD3(+) cells and 77.4% of CD25(+) cells). This reduction in activated T cells was accompanied by a marked reduction in HLA-DR expression by epidermal keratinocytes. CONCLUSIONS: CDS is a highly effective and remittive treatment for moderate to severe plaque-type psoriasis, leading to a reversal of both pathologic epidermal and immunologic activation.

Adult↗
PubMed2003

The Epstein-Barr virus SM protein induces STAT1 and interferon-stimulated gene expression.

Viruses utilize numerous mechanisms to counteract the host's immune response. Interferon production is a major component of the host antiviral response. Many viruses, therefore, produce proteins or RNA molecules that inhibit interferon-induced signal transduction pathways and their associated antiviral effects. Surprisingly, some viruses directly induce expression of interferon-induced genes. SM, an early lytic Epstein-Barr virus (EBV) nuclear protein, was found to specifically increase the expression of several genes (interferon-stimulated genes) that are known to be strongly induced by alpha/beta interferons. SM does not directly stimulate alpha/beta interferon secretion but instead induces STAT1, an intermediate step in the interferon signaling pathway. SM is a posttranscriptional activator of gene expression and increases STAT1 mRNA accumulation, particularly that of the functionally distinct STAT1beta splice variant. SM expression in B lymphocytes is associated with decreased cell proliferation but does not decrease cell viability or induce cell cycle arrest. These results indicate that EBV can specifically induce cellular genes that are normally physiological targets of interferon by inducing components of cytokine signaling pathways. Our findings therefore suggest that some aspects of the interferon response may be positively modulated by infecting viruses.

B-Lymphocytes↗
PubMed2003

Shoe contact dermatitis in Israel.

BACKGROUND: Patch testing with the shoe series may be useful for the diagnosis of shoe contact dermatitis. OBJECTIVE: The aim of the study was to verify the usefulness of the shoe series and the association of fungal infection with positive results in the shoe series. METHODS: A total of 140 patients with suspected shoe contact dermatitis underwent patch testing with the standard series and shoe series; 41 underwent mycologic examination. RESULTS: Positive results in the shoe series were noted in 58 patients (41.4%). The most common allergens were potassium dichromate (27.2%), nickel sulfate (11.9%), Kathon CG (10.9%), and 4-tert-butylphenol formaldehyde resin (8.7%). Of the 41 patients with suspected tinea pedis, 13 (32%) had positive mycologic findings and 9 (69.2%) also had a positive response to the shoe series. Of the patients with a negative result on mycologic examination, only 10 (35.7%) had a positive result in the shoe series. CONCLUSION: Our study indicates that all patients with foot dermatitis should undergo patch testing with the shoe series. Positive results in the shoe series seem to be more prevalent in patients with a fungal infection.

Adolescent↗
PubMed2003

Subtotal parathyroidectomy: a possible treatment for calciphylaxis.

Calciphylaxis is a rare disorder in patients with chronic renal failure that is characterized by ischemic necrotic skin lesions. The prognosis is grave and mortality is high (80%). The precise mechanism of calciphylaxis is still unknown, but in addition to chronic renal failure, elevated parathyroid hormone levels appear to play a role. The role of parathyroidectomy in treating affected patients is questionable. In this article, we describe the case of a patient with chronic renal failure who developed rapidly progressive subcutaneous calcifications and ulcerations in the lower extremities. These lesions regressed following subtotal parathyroidectomy. We also review the literature on calciphylaxis, with a focus on treatment options.

Biopsy, Needle↗
PubMed2002

Arginine methylation of STAT1 regulates its dephosphorylation by T cell protein tyrosine phosphatase.

Transcriptional induction by interferons requires the tyrosine and serine phosphorylation of the STAT1 transcription factor as well as its amino-terminal arginine methylation. Here we show that arginine methylation of STAT1 controls the rate of STAT1 dephosphorylation by modulating its interaction with PIAS1 and the nuclear tyrosine phosphatase TcPTP. Inhibition of STAT1 arginine methylation, or mutation of STAT1 Arg-31, results in a prolonged half-life of STAT1 tyrosine phosphorylation. This effect appears to be mediated by an increased binding of PIAS1 to STAT1 in the absence of STAT1 arginine methylation and a concomitant decrease in the association of STAT1 with TcPTP. Furthermore, inhibitors of arginine methylation require the presence of PIAS1 to exert their negative regulatory effect on the dephosphorylation of STAT1.

Animals↗
PubMed2002

Identification of a nuclear Stat1 protein tyrosine phosphatase.

Upon interferon (IFN) stimulation, Stat1 becomes tyrosine phosphorylated and translocates into the nucleus, where it binds to DNA to activate transcription. The activity of Stat1 is dependent on tyrosine phosphorylation, and its inactivation in the nucleus is accomplished by a previously unknown protein tyrosine phosphatase (PTP). We have now purified a Stat1 PTP activity from HeLa cell nuclear extract and identified it as TC45, the nuclear isoform of the T-cell PTP (TC-PTP). TC45 can dephosphorylate Stat1 both in vitro and in vivo. Nuclear extracts lacking TC45 fail to dephosphorylate Stat1. Furthermore, the dephosphorylation of IFN-induced tyrosine-phosphorylated Stat1 is defective in TC-PTP-null mouse embryonic fibroblasts (MEFs) and primary thymocytes. Reconstitution of TC-PTP-null MEFs with TC45, but not the endoplasmic reticulum (ER)-associated isoform TC48, rescues the defect in Stat1 dephosphorylation. The dephosphorylation of Stat3, but not Stat5 or Stat6, is also affected in TC-PTP-null cells. Our results identify TC45 as a PTP responsible for the dephosphorylation of Stat1 in the nucleus.

Animals↗
PubMed2002

Signal transduction by type I interferons.

The two classes of interferons, type I (IFNalpha, IFNbeta, IFNomega, and IFNtau) and type II (IFNgamma) are pleiotropic cytokines that exhibit antiviral, antiproliferative, and immunomodulatory effects on their target cells. This article summarizes the advances made in elucidating the molecular events that mediate the biological responses to type I interferons.

Active Transport, Cell Nucleus↗
PubMedDate not supplied

Protein binding and its potential for eliciting minimal systemic side effects with a novel inhaled corticosteroid, ciclesonide.

Freely circulating, protein unbound, active inhaled corticosteroid (ICS) can cause systemic adverse effects. Desisobutyryl-ciclesonide (des-CIC) is the active metabolite of ciclesonide, an effective, novel ICS for persistent asthma. This study examines the free fraction of ciclesonide and des-CIC and determines whether the presence of other agents or disease states affects protein binding. Protein binding of des-CIC (0.5, 5.0, 25, 100, and 500 ng/mL) was determined, using both equilibrium dialysis and ultrafiltration, in plasma from humans (healthy and either renally or hepatically impaired) and several animal species and in the presence of either salicylates or warfarin. Dialyzed samples were analyzed by liquid chromatography with tandem mass spectroscopy to determine both free and bound concentrations of des-CIC. After ultrafiltration, spiked plasma plus H-des-CIC was separated into free and bound fractions by centrifugation and quantified by scintillation counting. Additionally, in another study, protein binding of ciclesonide was determined by equilibrium dialysis. For equilibrium dialysis, the mean percentages of des-CIC (0.5-500 ng/mL) plasma protein binding across species were high, approximately 99%, and no apparent saturation of protein binding was observed. Results were similar for ultrafiltration analysis. Protein binding of des-CIC did not change in the presence of warfarin or salicylates or in the plasma of renally or hepatically impaired patients. The protein binding of ciclesonide was 99.4% in human serum. The very low fraction of unbound des-CIC in the systemic circulation suggests minimal systemic exposure of unbound des-CIC, thus suggesting a low potential for systemic adverse effects after administration of inhaled ciclesonide.

Animals↗