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Uzi Gafter

Publications and source records attributed to Uzi Gafter.

28 records · Page 2Linked to original sources
PubMed2003

The effects of weight loss on renal function in patients with severe obesity.

Severe obesity is associated with increased renal plasma flow (RPF) and glomerular filtration rate (GFR). The aim of the present study was to examine whether weight loss may reverse glomerular dysfunction in obese subjects without overt renal disease. Renal glomerular function was studied in eight subjects with severe obesity (body mass index [BMI] 48.0 +/- 2.4) before and after weight loss. Nine healthy subjects served as controls. GFR and RPF were determined by measuring inulin and PAH clearance. In the obese group, GFR (145 +/- 14 ml/min) and RPF (803 +/- 39 ml/min) exceeded the control value by 61% (90 +/- 5 ml/min, P = 0.001) and 32% (610 +/- 41 ml/min, P < 0.005), respectively. Consequently, filtration fraction was increased. Mean arterial pressure, although normal, was higher than in the control group (101 +/- 4 versus 86 +/- 2 mmHg, P < 0.01). After weight loss, BMI decreased by 32 +/- 4%, to 32.1 +/- 1.5 (P = 0.001). GFR and RPF decreased to 110 +/- 7 ml/min (P = 0.01) and 698 +/- 42 ml/min (P < 0.02), respectively. Albumin excretion rate decreased from 16 microg/min (range, 4 to 152 microg/min) to 5 microg/min (range, 3 to 37 microg/min) (P < 0.01). Fractional clearance of albumin decreased from 3.2 x 10(-6) (range, 1.1 to 23 x 10(-6)) to 1.2 x 10(-6) (range, 0.5 to 6.8 x 10(-6)) (P < 0.02). This study shows that obesity-related glomerular hyperfiltration ameliorates after weight loss. The improvement in hyperfiltration may prevent the development of overt obesity-related glomerulopathy.

Adult↗
PubMed2003

Cyclosporin A-induced hair growth in mice is associated with inhibition of calcineurin-dependent activation of NFAT in follicular keratinocytes.

One of the most common side effects of treatment with cyclosporin A (CsA) is hypertrichosis. This study shows that calcineurin activity is associated with hair keratinocyte differentiation in vivo, affecting nuclear factor of activated T cells (NFAT1) activity in these cells. Treatment of nude or C57BL/6 depilated normal mice with CsA inhibited the expression of keratinocyte terminal differentiation markers associated with catagen, along with the inhibition of calcineurin and NFAT1 nuclear translocation. This was associated with induction of hair growth in nude mice and retardation of spontaneous catagen induction in depilated normal mice. Furthermore, calcineurin inhibition blocked the expression of p21(waf/cip1) and p27(kip1), which are usually induced with differentiation. This was also associated with an increase in interleukin-1alpha expression (nude mice), a decrease in transforming growth factor-beta (nude and normal mice), and no change in keratinocyte growth factor expression in the skin. Retardation of catagen in CsA-treated mice was accompanied by significant alterations in apoptosis-related gene product expression in hair follicle keratinocytes. The ratio of the anti-apoptotic Bcl-2 to proapoptotic Bax expression increased, and expression of p53 and interleukin-1beta converting enzyme activity decreased. These data provide the first evidence that calcineurin is functionally active in follicular keratinocytes and that inhibition of the calcineurin-NFAT1 pathway in these cells in vivo by CsA enhances hair growth.

Animals↗
PubMed2003

Lower extremity amputations in chronically dialysed patients: a 10 year study.

BACKGROUND: Lower limb critical ischemia is a major problem in dialysed patients. OBJECTIVE: To evaluate the results of revascularization procedures, amputations and prosthetic rehabilitation in dialysed amputees. METHODS: In this retrospective study we examined the charts of selected dialysis patients. Forty-eight patients had undergone major amputation (4.5% of the dialysis population), and 24 patients entered the rehabilitation program. Widespread arterial calcification was common and led to falsely elevated ankle-brachial pressure indices in 9 of 14 limbs. Eight patients underwent revascularization. Subsequent major amputation was carried out 4 +/- 4.5 months after the revascularization (above knee in 5 patients and below knee in 3). Of the 16 patients who underwent primary amputation, only 2 were above-knee amputees. Seven patients with toe or metatarsal amputation went on to a major amputation 1.8 +/- 1.2 months after the distal amputation. RESULTS: No differences were found between diabetic and non-diabetic patients regarding the number of revascularization operations performed, the level of major amputation, or overall survival. Prosthetic rehabilitation was considered successful in 12 patients, partially successful in 8, and failed in 4 patients. Patient survival time was shortest in those patients with failed rehabilitation. A younger age confirmed favorable rehabilitation results, while long-standing diabetics and bilateral amputees were poor rehabilitation candidates. Patients who underwent primary amputation had more successful rehabilitation. A comparison between 24 dialysed amputees and 138 non-uremic amputees revealed similar rehabilitation results, although hospitalization time was longer in the dialysed patients. CONCLUSIONS: Early definitive therapy is essential when dealing with critical ischemia. After diagnostic angiography, proximal revascularization should be performed where feasible. Primary amputation is indicated in patients with extensive foot infection or gangrene. Prosthetic rehabilitation is warranted in most dialysed amputees.

Adult↗
PubMed2002

Anti-IL-10 therapeutic strategy using the immunomodulator AS101 in protecting mice from sepsis-induced death: dependence on timing of immunomodulating intervention.

The role of IL-10 in experimental sepsis is controversial. The nontoxic immunomodulator, ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) has been previously shown to inhibit IL-10 expression at the transcriptional level. In this study, we show that in mice subjected to cecal ligation and puncture (CLP), treatment with AS101 12 h after, but not before, CLP significantly increased survival of septic mice. This was associated with a significant decrease in serum IL-10 and in IL-10 secretion by peritoneal macrophages 24-48 h after CLP. At that time, the ability of these cells to secrete TNF-alpha and IL-1beta was restored in AS101-treated mice. The increased survival of AS101-treated mice was due to the inhibition of IL-10, since cotreatment with murine rIL-10 abolished the protective activity of AS101. AS101 increased class II Ag expression on peritoneal macrophages, severely depressed in control mice, while it did not affect the expression of class I Ags. This was accompanied by a significant elevation in the level of IFN-gamma secreted by splenocytes. Moreover, AS101 ameliorated bacterial clearance in the peritoneum and blood and decreased severe multiple organ damage, as indicated by clinical chemistry. Furthermore, myeloperoxidase levels in the liver and lung of AS101-treated mice, an indirect means of determining the recruitment of neutrophils, were significantly decreased. We suggest that nontoxic agents such as AS101, with the capacity to inhibit IL-10 and stimulate macrophage functions, may have clinical potential in the treatment of sepsis, provided they are administered during the phase of sepsis characterized by immune suppression.

Adjuvants, Immunologic↗
PubMed2002

The contribution of an arteriovenous access for hemodialysis to left ventricular hypertrophy.

BACKGROUND: The long-term isolated contribution of hemodialysis arteriovenous access (AVA) to cardiac hemodynamics has not been previously investigated in a prospective manner. METHODS: Twelve predialysis patients were studied before and 1 and 3 months after creation of a primary AVA. Evaluation included relevant clinical parameters, echocardiographic studies, and hemodynamic hormones. RESULTS: After creation of an AVA, there was no change in patient weight, blood pressure or hemoglobin level. Cardiac index increased and systemic vascular resistance decreased. Left ventricular mass (LVM) corrected to height increased from 63.8 +/- 5.5 to 68.9 +/- 4.9 g/m(2.7) at 1 month (P = 0.05) and 72.5 +/- 8.9 g/m(2.7) at 3 months (P < 0.05). This increase in LVM was accounted for mostly by an increase in interventricular septal thickness, whereas left ventricular end-diastolic diameter and posterior wall thickness did not change. The incidence of left ventricular hypertrophy (LVH) increased from 67% at baseline to 83% and 90% at 1 and 3 months, respectively. Left atrial area increased from 17.6 +/- 1.0 cm(2) at baseline to 19.7 +/- 1.3 cm(2) at 1 month (P < 0.01) and 20.2 +/- 1.2 cm(2) at 3 months (P < 0.05). Early diastolic transmitral flow increased from 68.0 +/- 4.2 cm/s at baseline to 85.6 +/- 7.3 and 89.2 +/- 6.5 cm/s at 1 and 3 months, respectively (P < 0.01). Inferior vena cava diameter increased at 1 month and did not change at 3 months. Plasma atrial natriuretic polypeptide levels increased from 268 +/- 35 pg/mL (87 +/- 11 pmol/L) at baseline to 461 +/- 63 pg/mL (150 +/- 20 pmol/L) at 1 month (P < 0.01) and 610 +/- 96 pg/mL (198 +/- 31 pmol/L) at 3 months (P < 0.01). Plasma renin activity and serum aldosterone levels decreased. Plasma angiotensin II, angiotensin-converting enzyme, and endothelin levels did not change. CONCLUSION: Creation of a hemodialysis AVA is independently associated with further progression of already existing LVH.

Adult↗
PubMed2002

DNA repair in mononuclear cells: role of serine/threonine phosphatases.

Treatment with cyclosporin A (CsA) in kidney-transplant recipients is associated with reduced DNA repair and enhanced cancer incidence. CsA is an inhibitor of the serine/threonine phosphatase calcineurin, also termed PP2B, which is a Ca(2+)/calmodulin-dependent phosphatase. In this study we sought to elucidate the role of calcineurin in DNA repair using CsA and tacrolimus; examine whether UV-induced DNA repair is associated with dephosphorylation; and investigate whether phosphatases other than calcineurin are active in DNA repair, in light of the fact that calcineurin inhibition only partially suppressed DNA repair. Peripheral blood mononuclear cells from healthy donors were used. In vitro, we assayed UV-induced DNA repair by measuring the incorporation of tritiated thymidine in UV-irradiated cells. We gauged phosphatase activity indirectly by measuring free inorganic phosphate (Pi) excreted into the medium. The phosphatase assay was performed under the same conditions and in parallel to the DNA-repair assay. Tacrolimus, like CsA, inhibited DNA repair in a dose-dependent fashion. DNA repair was associated with production of Pi, which correlated with the number of cells performing DNA repair. Phosphatase activity increased after UV irradiation. DNA repair correlated directly with phosphatase activity, whereas CsA reduced both DNA repair and Pi production. Inhibition of calmodulin by trifluoperazine and W7 [N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide] reduced DNA repair in part. We investigated the role of the Ca(2+)-independent phosphatases PP1 and PP2A using specific inhibitors. Calyculin A, which inhibits both phosphatases, reduced DNA repair. Endothall, a PP2A inhibitor, had no effect on DNA repair. Okadaic acid, which is mostly a PP2A inhibitor but also a weak inhibitor of PP1, reduced DNA repair only slightly. We suggest that DNA repair is mediated by way of Ca(2+)-dependent and Ca(2+)-independent pathways, with calcineurin and PP1 being the respective phosphatases involved in each pathway.

Calcineurin↗
PubMed2002

Effect of increased dialysate volume on peritoneal surface area among peritoneal dialysis patients.

Large dialysate volumes are often required to increase solute clearance for peritoneal dialysis patients. The resulting increase in solute clearance might be attributable to an increased plasma-to-dialysate concentration gradient and/or to an increased effective peritoneal surface area. One of the factors affecting the latter is the peritoneal surface area in contact with dialysate (PSA-CD). The aim of this study was to estimate the change in PSA-CD after a 50% increase in the instilled dialysate volume for patients undergoing peritoneal dialysis. PSA-CD was estimated by using a method applying stereologic techniques to computed tomographic (CT) scans of the peritoneal space. The peritoneal cavity of 10 peritoneal dialysis patients was filled with a solution containing dialysate, half-isotonic saline solution, and contrast medium. Peritoneal function tests and CT scanning of the abdomen were performed twice for each patient (with an interval of 1 wk), after instillation of a 2- or 3-L solution. Scanning of thin helical CT sections was performed, and 36 random sections of the abdomen were obtained after reconstruction. A grid was superimposed on the sections. The surface area was estimated by using stereologic methods. After instillation of the 2-L solution, the volume of the peritoneal solution at the time of CT scanning was 2.32 +/- 0.05 L. The PSA-CD was 0.57 +/- 0.03 m(2), ranging from 0.41 to 0.76 m(2). The use of the 3-L solution increased the peritoneal volume by 46 +/- 2%. PSA-CD increased by 18 +/- 2.3% to 0.67 +/- 0.04 m(2) (range, 0.49 to 0.84 m(2); P < 0.01). Creatinine mass transfer increased from 112 +/- 10 mg to 142 +/- 11 mg (P < 0.0001). The slope of the change of the plasma-to-dialysate creatinine concentration gradient with time decreased from -2.26 +/- 0.23 x 10(-2) to -1.97 +/- 0.16 x 10(-2) (P = 0.01). K(BD-0) (permeability-surface area product or mass area transfer coefficient at time 0 of the dwell) increased from 10.6 +/- 0.7 to 13.6 +/- 1.2 ml/min (P < 0.02). These data demonstrate that increasing the instilled dialysate volume by 50% for peritoneal dialysis patients results in significant increases in the PSA-CD and K(BD).

Adult↗
PubMed2002

Using the automated biopsy gun with real-time ultrasound for native renal biopsy.

BACKGROUND: The use of an automated biopsy system for renal biopsy has recently gained popularity, but its safety in single functioning kidneys is unclear. OBJECTIVE: To report our experience with the automated system for closed renal biopsy during a 5 year period. METHODS: Eighty-five patients underwent percutaneous native renal biopsy with the automated biopsy gun (16G needle) under real-time ultrasound. They were chronologically divided into two groups: 41 patients (group A), using an older ultrasound machine; and 44 patients (group B), using a newer ultrasound machine. Nine patients biopsied with a manual 14G Tru-cut needle served as the control (group C). RESULTS: The number of "attempted" passes at the kidney was 4.0 +/- 0.1 in group B, 4.7 +/- 0.3 in group A (P < 0.05 vs. group B), and 5.8 +/- 0.5 in group C (P < 0.01 vs. group B). The number of successful passes did not differ (3.3 +/- 0.1, 3.3 +/- 0.1, 3.1 +/- 0.2). The ratio of "attempted/successful" was 1.28 +/- 0.07 in group B, 1.95 +/- 0.38 in A, and 1.90 +/- 0.21 in C (P < 0.01 vs. B). The number of glomeruli obtained was similar in the three groups. Adequate tissue was obtained in 95%, 98%, and 100%, respectively. Hemoglobin decreased by 4.3 +/- 1.1% in group B, 6.9 +/- 1.3% in group A, and 11.3 +/- 1.8% in group C (P < 0.05 vs. B). Perinephric/subcapsular hematoma occurred in 5 patients (11.4%) in group A (2 taking aspirin), in 2 patients (4.9%) in group B, and in none in group C. The necessity for blood transfusion post-biopsy was similar in all groups. Four of five patients with single functioning kidneys (one in group A and four in group B) had uneventful biopsies, and adequate tissue was obtained in three. CONCLUSIONS: The use of the automated biopsy gun is effective, safe and has a low rate of major complications. It may be used safely in single functioning kidneys.

Adolescent↗