Celiac territory ischemic syndrome in a patient on chronic hemodialysis.

Mesenteric ischemia among chronic dialysis patients is usually of the nonocclusive type. Chronic occlusive mesenteric ischemia has been reported rarely in the dialysis population. The subset of"celiac-territory ischemic syndrome" has not been described in dialysis. The current report involves a 66-year-old female on chronic dialysis for 11 years. She experienced abdominal pain following sessions of hemodialysis, that later became more pronounced after eating. Abdominal angiography showed heavily calcified aorta, celiac trunk and superior mesenteric artery (SMA), with a 50% narrowing of the celiac and superior mesenteric arteries. During the following 9 months the symptoms worsened and weight loss set in. She was admitted with an episode of upper abdominal pain. Acalculous cholecystitis was found, along with multiple gastric and duodenal erosions including the second part, with an antral ulcer and multiple duodenal bulb ulcers. Repeated abdominal angiography showed progression of the stenotic lesions with significant narrowing of both the celiac trunk and the SMA. A stent was placed in the SMA. Following the procedure, the patient noted marked symptomatic improvement. On follow-up gastroduodenoscopy, all ischemic ulcers had healed completely. Serum albumin rose from a nadir of 31 to 40 g/l, and an extremely elevated c-reactive protein of 205,000 microg/l returned to normal (8,000 microg/l). The diagnosis of chronic occlusive mesenteric ischemia should be suspected among dialysis patients with post-prandial pain and weight loss in the face of calcified vessels. Predominant celiac territory ischemic syndrome presents as gastric and duodenal erosions and ulcers with or without acalculous cholecystitis.

Elevated serum alkaline phosphatase levels in a renal transplant patient precede colitis.

An asymptomatic, but highly significant, rise in serum alkaline phosphatase (AP) levels developed in a renal transplant recipient. Investigations ruled out bony or hepatobiliary disease. Subsequent diarrhea and weight loss led to a diagnosis of cytomegalovirus (CMV) colitis, which was confirmed with a positive CMV pp65 antigenemia test and an endoscopic finding of multiple colonic erosions. Intravenous ganciclovir led to complete patient recovery and a swift reduction of serum AP levels to normal. Normally, intestinal AP isoenzymes are cleared quickly from the circulation. However, acute bowel diseases, especially when inflammatory in origin, can produce high serum AP levels. In this presented patient, the rise in serum AP levels preceded symptomatic manifestations of CMV colitis, and fell with successful therapy. Acute CMV disease in solid organ transplant recipients is common, can take many shapes, and needs to be diagnosed quickly. An unexplained rise in serum AP levels should lead to a search for inflammatory bowel disease, specifically CMV colitis, in transplanted patients.

Hepatitis C infection in dialysis patients in Israel.

BACKGROUND: Hepatitis C virus is the major cause of acute and chronic hepatitis in patients with end-stage renal disease receiving replacement therapy. OBJECTIVES: To define the prevalence of HCV RNA in a population of patients on dialysis in Israel, to determine the relative risk of acquiring HCV infection while treated by hemodialysis or chronic ambulatory peritoneal dialysis, and to define the HCV genotypes in this population. METHODS: During 1995 we studied 162 dialysis patients. Information was obtained regarding the mode of dialysis, years of treatment, number of blood transfusions, and results of serological testing for HCV, hepatitis B virus, and human immunodeficiency virus. Anti-HCV antibodies were tested by a third-generation microparticle enzyme immunoassay. HCV RNA was determined by polymerase chain reaction. HCV genotyping was performed by a hybridization assay. RESULTS: HCV RNA was detected in 18% of the HD group and 7% of the CAPD group. The number of HCV RNA-positive patients was significantly higher in the HD than the CAPD group (P < 0.05). HCV RNA-positive HD patients were treated longer than the HCV RNA-negative patients (P < 0.02). CONCLUSIONS: Third-generation immunoassay proved to be highly sensitive (94%) and specific (91%) in identifying HCV RNA positivity. Several HCV subtypes were detected, 1b being the most frequent. Identification and isolation of infected HCV patients may minimize its spread in dialysis units and prevent cross-infection.

Peritonitis due to Thermoascus taitungiacus (Anamorph Paecilomyces taitungiacus).

The first case of human disease due to the thermophilic ascomycete Thermoascus taitungiacus (the teleomorph of Paecilomyces taitungiacus) is presented. T. taitungiacus was recovered from four dialysate fluid specimens of a 57-year-old patient undergoing chronic peritoneal dialysis. Identification was based upon cylindrical conidia, reddish orange nonostiolate ascomata, lack of growth at 20 degrees C, thermotolerance, and ascospores that appeared pale yellow, elliptical, thick walled, and predominately echinulate by light microscopy but irregularly verrucose by scanning electron microscopy.

Effect of cyclosporin A on DNA repair and cancer incidence in kidney transplant recipients.

Cancer incidence is enhanced in transplant recipients. Decreased DNA repair ability is associated with increased cancer incidence. Transplanted patients with cancer were found to have reduced DNA repair. We hypothesized that immunosuppressive therapy may impair DNA repair and thus contribute to the increased cancer incidence in transplanted patients. The objectives of this study were (1) to investigate the effect of two immunosuppressive treatment protocols on DNA repair in kidney transplant recipients; (2) to evaluate the cancer incidence in these patients; and (3) to study the in vitro effect of cyclosporin A (CsA), azathioprine, and prednisolone-separately and in various combinations-on DNA repair. Three groups were studied: (1) a control group; (2) patients treated with azathioprine and prednisone (double-therapy group); and (3) patients treated with CsA, azathioprine, and prednisone (triple-therapy group). The two patient groups did not differ in age, gender, time on dialysis before transplantation, or kidney function or in the number of acute rejections. However, the interval from transplantation to the DNA repair study was shorter in the triple-therapy group (P <.01). DNA repair was induced in peripheral blood mononuclear cells (PBMCs) by ultraviolet irradiation and expressed as tritiated thymidine uptake by these cells. DNA repair in the triple-therapy group was 679 +/- 64 cpm/10(6) cells, significantly less than that in the control group (1049 +/- 69 cpm/10(6) cells, P <.02). In the double-therapy group, DNA repair was similar to that in the control group. The follow-up period was shorter in the triple-therapy group (116 +/- 19 months vs 174 +/- 29 months, P <.01). Five tumors developed in the triple-therapy group, but only one developed in the double-therapy group (P =.05). The in vitro study showed a dose-dependent reduction in PBMC DNA repair by CsA. Azathioprine and prednisolone reduced DNA repair slightly, but CsA reduced DNA repair significantly more than either one or a combination of them. In summary, triple therapy was associated with impaired PBMC DNA repair and increased cancer incidence. CsA was responsible in large part for the reduction in DNA repair ability found in the in vitro and in vivo studies. This may have partly contributed to the enhanced cancer incidence in the kidney transplant recipients.

Sonographic features of dialysis-related amyloidosis of the shoulder.

This study evaluated the diagnostic role of ultrasonography in dialysis-related amyloidosis in shoulders of chronically hemodialyzed patients. Fourteen shoulders of 12 long-term hemodialysis patients were examined. All patients had been on dialysis for at least 10 years. All patients had varying degrees of pain and limitations of movement in the studied shoulders. Dialysis-related amyloidosis was the presumed diagnosis in all patients. Any patient with a history of any disease, other than dialysis-related amyloidosis, capable of producing a pathologic shoulder condition was excluded. The following parameters were studied: supraspinatus and biceps tendon thickness, tendon tears, synovial thickening, and the presence of hypoechoic material around tendons and within bursae. All shoulders had a nonhomogeneous thickening, greater than 7 mm, of the supraspinatus tendon. Seven shoulders (50%) had abnormal thickening of the biceps tendon (4 mm or greater), and two shoulders had abnormal thickening of the subscapularis tendon. Hypoechoic deposits were seen in the subdeltoid bursae and biceps sheaths in five and six shoulders, respectively. Three shoulders showed partial tears of the supraspinatus tendon, one shoulder showed a tear in the biceps tendon, and one shoulder had a tear in the subscapularis tendon. Ultrasonography is an excellent imaging modality in diagnosing the presence of dialysis-related amyloidosis in symptomatic shoulders of long-term hemodialysis patients, without having to resort to invasive procedures. The results of previous studies have been confirmed and new ultrasonographic findings described. Of particular interest is the involvement of the subscapularis tendon in dialysis-related amyloidosis. Repeat ultrasonography can become an important way to follow-up progression of shoulder dialysis-related amyloidosis in hemodialyzed patients.

Haemolysis in haemodialysis patients: evidence for impaired defence mechanisms against oxidative stress.

BACKGROUND: Uraemic patients have a decreased ability to withstand oxidative stress. It is postulated that their antioxidant capacity is reduced, yet the mechanism remains unclear. Recently 33 haemodialysis (HD) patients were exposed to chloramine contamination in the water supply. This led to haemolysis in 24 patients, while nine were unaffected. In the former group haemoglobin decreased from 11.7+/-1.1 to 8.5+/- 1.4 g/dl (P<0.0001) and returned to 11.4+/-0.9 g/dl (P<0.0001) following recovery. During haemolysis, haptoglobin was 38.4+/-10.6 vs 138.1+/-8.3 ng/dl (P<0.0001) following recovery. METHODS: To explore the factors affecting the severity of haemolysis we studied extracellular and intracellular anti-oxidant defence mechanisms 3 months after recovery. In 29 patients and 20 controls we determined plasma glutathione (GSH), and the erythrocyte enzymes glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rx), and superoxide dismutase (SOD). Serum malondialdehyde (MDA) was measured as a marker of oxidative stress. RESULTS: Plasma GSH was lower in patients as compared to controls (5.49+/-0.26 vs 7.4+/-0.5 micromol/l, P<0.005). There was an inverse correlation between GSH and the degree of haemolysis (r=-0.42, P<0.02). Patients had higher GSH-Rx (4.64+/-0.15 vs 3.97+/-0.12 U/gHb, P<0.02), lower GSH-Px (29. 7+/-1.85 vs 35.5+/-1.62 U/gHb, P<0.001), and similar SOD (0.63+/-0. 02 vs 0.51+/-0.02 U/mgHb) as compared to controls. There was no correlation between the enzyme levels and the degree of haemolysis. MDA was higher in patients (2.37+/-0.07 vs 0.97+/-0.1 nmol/ml, P<0. 0001). There was a correlation between MDA and the years patients were on HD (r=0.43, P<0.02). CONCLUSIONS: These data indicate that HD patients have an impaired anti-oxidant response, which may be attributed in part, to plasma GSH deficiency. Patients with the lowest plasma GSH levels are more susceptible to oxidative stress and consequent haemolysis.

Glomerular hemodynamics in severe obesity.

Differential solute clearances were used to characterize glomerular function in 12 nondiabetic subjects with severe obesity (body mass index >38). Nine healthy subjects served as the control group. In the obese group, glomerular filtration rate (GFR) and renal plasma flow (RPF) exceeded the control value by 51 and 31%, respectively. Consequently, filtration fraction increased. The augmented RPF suggested a state of renal vasodilatation involving, mainly or solely, the afferent arteriole. Albumin excretion rate and fractional albumin clearance increased by 89 and 78%, respectively. Oral glucose tolerance tests were suggestive of insulin resistance. Insulin resistance was positively correlated with GFR (r = 0.88, P<0.001) and RPF (r = 0.72, P <0.001). Mean arterial pressure was higher than in the control group. Fractional clearances of dextrans of broad size distribution tended to be lowered. The determinants of the GFR were estimated qualitatively by using a theoretical model of dextran transport through a heteroporous membrane. This analysis suggests that the high GFR in very obese subjects may be the result of an increase in transcapillary hydraulic pressure difference (DeltaP). An abnormal transmission of increased arterial pressure to the glomerular capillaries through a dilated afferent arteriole could account for the augmentation in DeltaP.

Lymphocytic intracellular calcium in a patient with complicated verapamil overdose.

Overdose with calcium channel blockers (CCBs) may lead to serious complications. CCBs act by blocking calcium entry into the cell, thus lowering intracellular calcium ([Ca2+]i). [Ca2+]i during CCB overdose has not yet been reported. We measured [Ca2+]i in lymphocytes of a patient with acute verapamil overdose with a complex clinical picture. A 59-year-old woman was admitted after a suicidal ingestion of 7200 mg of a sustained-release verapamil preparation. She presented with hypotension, complete atrioventricular block, stupor, hypokalemia, and hyperglycemia. Acute oliguric renal failure, acute pancreatitis, and the adult respiratory distress syndrome further complicated her medical course. Treatment was supportive and she recovered completely. Intracellular calcium ([Ca2+]i) was measured in the patient's lymphocytes using a spectrofluorometer with the calcium-sensitive dye Fura-2-acetoxymethyl ester. Thirty nine hours after the ingestion, [Ca2+]i was low at 52 nM (compared with 80 nM in a healthy control subject). Lymphocytic [Ca2+]i did not respond to stimulation with phytohemagglutinin (PHA). Fourteen days after the verapamil overdose, after the patient had recovered completely, lymphocytic [Ca2+]i was still low at 55 nM. At this time, there was an incomplete response to PHA in the lymphocytes. Three months after the ingestion, [Ca2+]i was normal, with a normal response to PHA. Verapamil overdose may run a complex clinical course, but full recovery is to be hoped for with full supportive care. Cellular intoxication, as reflected by low lymphocytic [Ca2+]i, is prolonged and lags behind the clinical recovery by weeks.

Erythropoietin, folic acid deficiency and hyperhomocysteinemia: is there a possible relationship in chronically hemodialyzed patients?

AIMS: To examine the possible relationships between recombinant human erythropoietin (rhEPO) therapy, serum folic acid and homocysteine levels in a cohort of stable, chronically hemodialyzed patients. MATERIAL AND METHODS: The study was cross-sectional in its first phase and consisted of 3 groups of subjects (group 1:6 healthy controls; group 2:7 dialyzed patients not receiving rhEPO; group 3: 14 patients on rhEPO therapy). Hematological and biochemical parameters were taken after an overnight fast in all subjects. The second phase of the study was prospective, and included 8 dialyzed patients, and investigated the effects of a 6-month period of folic acid supplementation (10 mg, 3 times a week) on the same parameters examined in the first phase of the study. RESULTS: In the first part of the study hemoglobin levels were near-normal, or normal, in all patients. No differences in hemoglobin or hematocrit values were observed in the 3 groups. 80% of all hemodialyzed patients had low serum folic acid levels, irrespective of whether they were receiving rhEPO. Serum erythropoietin level was elevated in group 3 (23.3+/-10.4 mIU/ml). In group 2, serum erythropoietin level was not different from that of the healthy controls (13.5+/-11.2 vs. 8.0+/-5.4 mIU/ml, p = n.s.). Total serum homocysteine levels were elevated in all dialyzed patients (group 2: 24.7+/-9.2 micromol/l; group 3: 31.6+/-14.4 micromol/l), with a significant difference seen when comparing controls and those dialyzed patients on rhEPO therapy (8.7+/-2.2 vs. 31.6+/-14.4 micromol/l; p<0.05). Significant correlations (ANOVA) were observed between serum erythropoietin and folic acid levels (r = -0.382; p = 0.049), and between folic acid and homocysteine levels (r = -0.560; p = 0.002). In the second part of the study folic acid supplementation led to a highly significant reduction in homocysteine levels (20.9+/-4.9 vs. 11.9+/-2.5 micromol/l; p<0.0005). Two of 3 patients receiving rhEPO therapy, had rhEPO discontinued after commencing folic acid, as hemoglobin levels remained adequate, even without rhEPO. CONCLUSIONS: In hemodialyzed patients, the presence of a near-normal hemoglobin level, irrespective of rhEPO therapy, implies efficient erythropoiesis. Without adequate folic acid reserves, folic acid deficiency may develop in these patients and this will aggravate already high homocysteine levels. Therefore, folic acid supplementation is warranted in hemodialyzed patients, especially in those patients with hemoglobin levels approaching normal. This treatment is safe and effective in reducing homocysteine levels, especially when given in high doses for prolonged periods of time.

Successful intradialytic parenteral nutrition after abdominal "Catastrophes" in chronically hemodialysed patients.

OBJECTIVE: To assess the therapeutic contribution of intradialytic parenteral nutrition (IDPN) in four acutely ill, hypercatabolic, hemodialysed patients. All underwent major surgery, complicated by infection and malnutrition. DESIGN: A retrospective clinical study. SETTING: An in-center hemodialysis unit, at a tertiary referral hospital. PATIENTS: Patient 1: a young woman, with a good renal transplant. Developed gastric lymphoma, which required gastrectomy. After cessation of immunosuppression, "lost" her kidney and returned to hemodialysis. Received IDPN for 4 months and recovered well from severe malnourishment. Patient 2: an elderly, malnourished man, on continuous ambulatory peritoneal dialysis (CAPD). Developed biliary peritonitis and bacteremia. In a 3-month period, the patient had four operations. Maintained on IDPN for 4 months. Patient 3: a young and obese man, who suffered from life-threatening staphylococcal aureus peritonitis, resulting in widespread bowel adhesions. Underwent repeated aspirations of purulent ascites, laparoscopy, and explorative laparotomy. IDPN was administered for 4 months and stopped on the patient's request. Patient 4: a young man, who after cadaveric renal transplantation remained hospitalized for 6 months because of acute rejection and peritoneal and retroperitoneal abscesses. Had major surgery performed seven times. Received IDPN for 6 months, and is now well. RESULTS: All four patients benefited from 4 to 6 months of IDPN, as an integral part of intensive supportive and nutritional treatment. Weight loss was halted, as patient appetite returned and oral nutrition became adequate. Estimated daily protein intake reached 1.2 g/kg, while caloric intake rose to nearly 30 kcal/kg/d (Table 3). Mean serum albumin levels increased from 25.5 g/L +/- 0.9 g/L to 38.0 g/L +/- 1.5 g/L. No adverse side effects were seen from IDPN. CONCLUSION: IDPN is a worthwhile part of treatments used in the catabolic, postoperative hemodialysed patient. It is safe and efficient when used over a 6-month period in trying to attenuate existing, or worsening malnutrition in these patients. It should be commenced at an early stage in these patients, after attempts at oral nutritional support have been deemed inadequate.

H2O2 induces DNA repair in mononuclear cells: evidence for association with cytosolic Ca2+ fluxes.

Cellular DNA repair systems are induced whenever DNA is damaged. Reactive oxygen species (ROS) are generated, in vivo, in the tissues as a result of regular cellular metabolism or after exposure to oxidizing agents, such as ultraviolet (UV) irradiation. It has been suggested that ROS mediate DNA damage. The objectives of the study were as follows: (1) to investigate whether hydrogen peroxide (H2O2), the commonly occurring cellular ROS, induces DNA repair as a response to the damage it probably causes; (2) to evaluate whether H2O2-induced DNA repair, if present, is signaled through a Ca2(+)-dependent pathway via the tyrosine kinase signal transduction. H2O2 was found to induce DNA repair in human peripheral blood mononuclear cells (PBMCs) in a dose-dependent manner. The recovery of RNA synthesis, which occurred after DNA repair, confirmed that transcribable DNA was repaired. The inhibition of tyrosine kinase activity by genistein reduced the DNA repair significantly. Furthermore, H2O2 caused a dose-dependent significant rise in cytosolic calcium ((Ca2+)i). H2O2 also induced a small rise in (Ca2+)i of cytosolic Ca2(+)-depleted cells, probably reflecting the release of Ca2+ from internal stores. Genistein inhibited both Ca2+ influx and Ca2+ release from internal stores. In summary, H2O2 induced a DNA repair synthesis that was in part Ca2+ dependent and signaled via tyrosine kinase. The changes in DNA repair paralleled changes in (Ca2+)i. The H2O2-induced (Ca2+)i rise was mostly the result of influx, but to some degree it was also due to the translocation of Ca2+ from internal stores.

Impaired lymphocyte calcium metabolism in end-stage renal disease: enhanced influx, decreased efflux, and reduced response to mitogen.

Lymphocytes from patients with end-stage renal disease (ESRD) exhibit elevated cytosolic calcium concentration ((Ca2+)i), but the mechanisms responsible for this elevated (Ca2+)i have not been entirely elucidated. In addition, lymphocyte proliferative responses to mitogenic stimuli are suppressed in patients with ESRD. The objectives of the study were as follows: (1) to measure calcium influx and efflux in lymphocytes from patients with ESRD; (2) to measure the effect of the calcium regulator parathyroid hormone (PTH) on lymphocyte (Ca2+)i; (3) to measure cytosolic calcium signal in patients' lymphocytes after mitogenic stimulation. The three study groups were as follows: healthy subjects (control), patients with chronic renal failure (CRF) before the beginning of regular dialysis treatment, and patients undergoing regular hemodialysis (HD) treatment. Peripheral blood lymphocytes were tested in vitro for (Ca2+)i, Ca2+ influx, and membrane calcium-adenosine triphosphatase (CaATPase) activity. Cytosolic Ca2+ signals were traced after stimulations by PTH and by phytohemagglutinin (PHA). Baseline (Ca2+)i was significantly elevated in both ESRD groups. Ca2+ influx was enhanced and CaATPase activity was reduced in both ESRD groups. PTH caused a (Ca2+)i increase in normal cells in a dose-dependent manner. PHA caused a (Ca2+)i elevation, with a Ca2+ signal in both groups of patients with ESRD that was significantly smaller than that in the control group. These findings suggest that the high (Ca2+)i found in lymphocytes from patients with ESRD is the result of enhanced Ca2+ influx concomitant with reduced Ca2+ extrusion, as reflected by reduced CaATPase activity. The patients' elevated serum PTH levels may have contributed to the high (Ca2+]i. The impaired cytosolic (Ca2+)i response to PHA may explain in part the suppressed lymphocyte proliferative response to PHA in patients with ESRD.