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Biomedical subjects

M Zlotnik

Publications and source records attributed to M Zlotnik.

At least 19 recordsLinked to original sources

Adenosine is upregulated during peritonitis and is involved in downregulation of inflammation.

Loss of function of the peritoneal membrane is associated with peritonitis. Adenosine levels in sites of inflammation were shown to increase and exhibit immunoregulatory effects. Our aim was to elucidate the regulatory role of adenosine during peritonitis and to test the involvement of peritoneal mesothelial cells (PMC) in adenosine regulation. In a mice model of Escherichia coli peritonitis, the adenosine A(2A) receptor (A(2A)R) agonist (CGS21680) prevented leukocyte recruitment and reduced tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels. Peritonitis induced the elevation of adenosine with a peak at 24 h. Analysis of adenosine receptor levels on peritoneum showed that A(1) receptor (A(1)R) protein levels peak at 12 h after inoculation and then return to baseline at 24 h, whereas high affinity A(2A)R protein levels peak at 24 h concomitantly with the peak of adenosine concentration. Low affinity A(2B) receptor (A(2B)R) levels elevated slowly, remaining elevated up to 48 h. In human PMC (HPMC), the early cytokines, IL-1-alpha, and TNF-alpha upregulated the A(2B) and A(2A) receptors. However, interferon-gamma (IFN-gamma) upregulated the A(2B)R and decreased A(2A)R levels. Treatment with the A(2A)R agonist reduced IL-1-dependent IL-6 secretion from HPMC. In conclusion, the kinetics of adenosine receptors suggest that at early stage of peritonitis, the A(1)R dominates, and later its dominance is replaced by the G stimulatory (Gs) protein-coupled A(2A)R that suppresses inflammation. Early proinflammatory cytokines are an inducer of the A(2A)R and this receptor reduces their production and leukocyte recruitment. Future treatment with adenosine agonists should be considered for attenuating the damage to mesothelium during the course of acute peritonitis.

Adenosine↗

Intraocular pressure during haemodialysis: a review.

OBJECTIVES: Although several works in the past have examined the effect of haemodialysis (HD) on intraocular pressure (IOP), reported findings, theories, and conclusions are very different. The objectives of this article are to resume the reported evidence of IOP changes during HD, to review the proposed hypothesis of HD influence on IOP, and to determine if ophthalmic examination is imperative in HD patients. METHODS: We analysed the peer-reviewed English literature and selected all possible relevant articles. RESULTS: The influence of HD on IOP is not clear, and even in recent studies opposite findings can be found. CONCLUSIONS: Future studies are needed to clarify the effects of HD on IOP. In patients with glaucoma or with predisposed narrow angles, or eyes with impaired aqueous outflow, the possibility of acute IOP rise during HD could be much more frequent than in normal patients. So in these patients, a more strict ophthalmic scheduled examination seems to be feasible.

Glaucoma↗

Surveillance of chronic haemodialysis-associated infections in southern Israel.

During a 12-month surveillance period, haemodialysis (HD) patients in southern Israel were categorised according to the type of vascular access site (VAS), i.e., arteriovenous (AV) fistula, synthetic AV graft, and cuffed or non-cuffed vascular catheters. Endpoints, expressed as cases/100 patient-months, were: incidence of hospital admission; antibiotic therapy; bloodstream infection (BSI); and VAS infection. These were compared to Centers for Disease Control (CDC) surveillance data, overall and by VAS type. In total, 2568 patient-months were analysed. The VAS distribution differed significantly from CDC data for fistulas (72% vs. 31%), grafts (12% vs. 41%), cuffed catheters (11% vs. 25%) and non-cuffed catheters (5% vs. 3%) (p < 0.0001 in all cases). Of 151 admissions, 32% resulted from infection, for which 112 antibiotic courses (22% vancomycin) were given. There were 16 BSIs, three involving resistant strains. The incidences of admission, antibiotic therapy, BSI and VAS infection were significantly lower overall, compared to CDC rates, as were most VAS-specific endpoints. These differences may be explained by VAS type distribution, although other factors may also be involved. Reporting regional or national surveillance data may allow a standardised comparison of the incidence of HD-associated infections.

Adolescent↗

Increased coagulation factor levels leading to allograft renal vein thrombosis.

A patient with end-stage kidney disease is described, who lost his renal allograft in the early post-transplant period due to allograft renal vein thrombosis. Prior to transplantation, he had been treated by hemodialysis and lost several vascular accesses because of thrombosis. A search for potential thrombophilic factors disclosed a unique combination of increased clotting factor levels, i.e. FVIII, FIX, FXI and homocysteine. More common hereditary and acquired hypercoagulability factors have been excluded in this patient. While clotting factor deficiencies are well known causes of hemophilia, their levels should also be measured in the workup of transplant candidates with a history of multiple vascular access thrombosis.

Blood Coagulation Factors↗

Cefuroxime-induced encephalopathy.

We describe four patients who developed an encephalopathic syndrome characterized by obtundation or stupor, myoclonic jerks, and asterixis in association with cefuroxime therapy. Three patients had renal failure. These cases suggest that cefuroxime in overdose or in conventional doses in patients with renal failure can cause a reversible encephalopathy. This syndrome may have been unrecognized because it usually occurs in severely ill patients with additional causes for encephalopathy.

Brain Diseases↗

Successful treatment of secondary hyperparathyroidism in hemodialysis patients with oral pulse 1-alpha-hydroxy-cholecalciferol therapy.

We have used high-dose oral pulse therapy with 1 alpha-hydroxycholecalciferol (1 alpha-OH-D3) to treat 40 hemodialysis patients suffering form secondary hyperparathyroidism. Forty patients with intact parathyroid hormone (PTH) levels of > 150 pg/ml were treated with 4 micrograms oral 1 alpha-OH-D3 twice weekly for 1 year. The mean PTH level was 515 +/- 50 pg/ml prior to treatment, which fell to 191 +/- 42 pg/ml after 6 months of treatment (p < 0.00001), and to 164 +/- 39 pg/ml after 12 months of treatment. Patients with very high PTH levels (> 800 pg/ml) suppressed less well than patients with lower levels (150-300 pg/ml). The therapeutic end point of PTH < 100 pg/ml was achieved in 23 patients (58%). The main side effect of the treatment was hypercalcemia, but this was symptomatic in only 3 patients, all above the age of 70 years. In summary, oral high-dose pulse therapy with 1 alpha-OH-D3 was highly effective in suppressing PTH levels in hyperparathyroid hemodialysis patients, and side effects were relatively few.

Administration, Oral↗

Inhibition of several strains of influenza virus in vitro and reduction of symptoms by an elderberry extract (Sambucus nigra L.) during an outbreak of influenza B Panama.

A standardized elderberry extract, Sambucol (SAM), reduced hemagglutination and inhibited replication of human influenza viruses type A/Shangdong 9/93 (H3N2), A/Beijing 32/92 (H3N2), A/Texas 36/91 (H1N1), A/Singapore 6/86 (H1N1), type B/Panama 45/90, B/Yamagata 16/88, B/Ann Arbor 1/86, and of animal strains from Northern European swine and turkeys, A/Sw/Ger 2/81, A/Tur/Ger 3/91, and A/Sw/Ger 8533/91 in Madin-Darby canine kidney cells. A placebo-controlled, double blind study was carried out on a group of individuals living in an agricultural community (kibbutz) during an outbreak of influenza B/Panama in 1993. Fever, feeling of improvement, and complete cure were recorded during 6 days. Sera obtained in the acute and convalescent phases were tested for the presence of antibodies to influenza A, B, respiratory syncytial, and adenoviruses. Convalescent phase serologies showed higher mean and mean geometric hemagglutination inhibition (HI) titers to influenza B in the group treated with SAM than in the control group. A significant improvement of the symptoms, including fever, was seen in 93.3% of the cases in the SAM-treated group within 2 days, whereas in the control group 91.7% of the patients showed an improvement within 6 days (p < 0.001). A complete cure was achieved within 2 to 3 days in nearly 90% of the SAM-treated group and within at least 6 days in the placebo group (p < 0.001). No satisfactory medication to cure influenza type A and B is available. Considering the efficacy of the extract in vitro on all strains of influenza virus tested, the clinical results, its low cost, and absence of side-effects, this preparation could offer a possibility for safe treatment for influenza A and B.

Adolescent↗

Elevated superoxide generation in mononuclear phagocytes by treatment with 1 alpha hydroxyvitamin D3: changes in kinetics and in oxidase cytosolic factor p47.

The effect of 1 alpha-hydroxyvitamin D3 (1 alpha OHD3) treatment on the superoxide production of phagocytic cells in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) was studied. A 3-day treatment of CAPD patients with 3 micrograms per day of 1 alpha OHD3 (high-dose treatment) significantly increased NADPH oxidase and killing activities in peritoneal macrophages and peripheral blood monocytes (P < 0.001) as compared with low-dose (0.25 microgram/day of 1 alpha OHD3) treatment or nontreatment. The high oxidase activity observed in macrophages and monocytes after the treatment with 1 alpha OHD3, correlated significantly to the increase in the amount of the cytosolic factor p47 of the NADPH oxidase as detected by western blotting analysis. Superoxide production by the peripheral blood neutrophils of these patients only slightly increased with 1 alpha OHD3 treatment, and the amount of p47 was not affected by 1 alpha OHD3 administration. In order to evaluate the significance of the oxidase cytosolic factor in dictating oxidase activity, a reconstitution of NADPH oxidase was conducted by mixing macrophage cytosols and membranes in a cell-free system. The addition of macrophage cytosol from patients on high-dose treatment to macrophage membranes from patients in all of the categories of treatment resulted in significantly higher (P < 0.001) superoxide production as opposed to the macrophage cytosol from nontreated patients. These results suggest that 1,25(OH)2D3 causes an increase in NADPH oxidase activity in the peritoneal macrophages and monocytes of CAPD patients by inducing synthesis and elevating the amount of the cytosolic factor p47.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcitriol↗

The effect of peritoneal dialysis fluid on the release of IL-1 beta and TNF alpha by macrophages/monocytes.

OBJECTIVE: To study the effect of dialysis fluid on the release of interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF alpha) by peritoneal macrophages (PM) and peripheral blood mononuclear cells (MNC), and the time course and factors involved in this effect. DESIGN: PM and MNC were incubated for various periods with Dianeal itself, or Dianeal of varying pH and composition. IL-1 beta was measured by radioimmunoassay and TNF alpha by cytotoxicity assay. PATIENTS: PM were obtained by centrifugation of dialysis effluent from 3 continuous ambulatory peritoneal dialysis (CAPD) patients. MNC were obtained from healthy volunteers. RESULTS: Dialysis fluid inhibited the release of both cytokines. Indomethacin had no effect on the inhibition of TNF alpha release caused by dialysis fluid. Thus prostaglandins are not involved in this inhibition. Solutions of pH 5.2 and high lactate concentration caused an identical inhibition to that caused by dialysate, whereas the presence or absence of glucose had no effect. Thus it seems that pH and lactate are the important inhibitory factors. Time course studies showed that the inhibition of TNF alpha release was substantial after only 15 minutes of incubation with dialysate, whereas the inhibition of IL-1 beta became significant only after 60 minutes of incubation. CONCLUSIONS: Even though dialysate pH rises within 15-30 minutes after instillation into the abdomen, the initial low pH present for only a short time could have a significant effect on TNF alpha release by peritoneal macrophages, and thus on their ability to mount a normal inflammatory response. Lactate also has a significant inhibitory role. It is suggested that commercial dialysis solutions should have a pH of 7.0 and that a physiological buffer other than lactate be used.

Cells, Cultured↗

[Calcific periarthritis in patients with endstage renal disease on chronic dialysis].

2 patients with end-stage renal disease undergoing dialysis developed calcific periarthritis. A 25-year-old man on hemodialysis developed arthritis of 2 right metacarpophalangeal joints and a 65-year-old man on chronic ambulatory peritoneal dialysis suffered from pain and tenderness in the left buttock. Treatment with nonsteroidal antiinflammatory drugs in the first case and periarticular injection of methylprednisolone (Depomedrol) in the second were successful.

Adult↗

Extreme hypermagnesemia due to ingestion of Dead Sea water.

We describe 3 patients who developed extreme hypermagnesemia due to ingestion of water of the Dead Sea, which would have been fatal were it not for the protective effects of the accompanying hypercalcemia. We emphasize the clinical features of this condition and the importance and effectiveness of early hemodialysis as the main modality of treatment.

Aged↗

Dialysis in renal failure casued by amyloidosis of familial Mediterranean fever. A report of ten cases.

Ten unselected patients with renal failure casued by amyloidosis associated with FMF were treated by regular hemodialysis therapy from 1969 to 1974. They were compared to age-matched control patients treated by hemodialysis in the same unit during the same period, who were suffering from renal failure caused by other disease. Mortality in FMF and control patients was 30% with no significant difference in mean survival, shunt life, serum albumin or hemoglobin levels between the two groups. There was no significant difference in blood pressure measured predialysis or postdialysis in patients with FMF or in controls. The synthetic ACTH stimulation test showed adequate or elevated adrenocortical function. It is concluded that life can be prolonged up to 3 1/2 years by hemodialysis in renal failure caused by amyloidosis complicating FMF, and that renal failure casued by FMF is not a contraindication to regular hemodialysis therapy.

Adrenocorticotropic Hormone↗

The aetiology of senile osteoporosis: secondary hyperparathyroidism due to renal failure.

The aetiology of senile osteoporosis was investigated in a series of elderly normal persons (mean age 76.8 years) who were compared to 18-19 year old normal controls. Osteoporosis was estimated by standard radiological morphometric and densitometric techniques, in the metacarpals and thoraco-lumbar vertebrae. Serum parathyroid hormone levels were significantly higher in the elderly group, and correlated well with morphometric and densometric measurements of osteoporosis. Creatinine clearance was reduced in seven out of nine of the elderly group, and correlated well with the degree of osteoporosis. Serum thyrocalcitonin levels were reduced in the elderly. Tubular reaborption of phosphate and TmP/GFR were in the hyperparathyroid range in the elderly group and correlated well with the degree of osteoporosis. The hypothesis is advanced that the osteoporosis of old age is a result of parathyroid overactivity, caused by asymptomatic chronic renal failure. The suggestion is made that a diet low in phosphorus might reduce the incidence of osteoporosis in old age by reducing the parathyroid overactivity.

Adolescent↗