Direct effects of volatile anesthetics on cardiac function.

The volatile anesthetics are a class of general anesthetic drugs used by the perfusionist during cardiopulmonary bypass (CPB). These agents are used in low doses in combination with other anesthetics to produce complete anesthesia. During CPB, these agents are capable of safely anesthetizing the paitent. It is well understood that these anesthetics act at the level of the central nervous system. However the intent of this study was to define the effects of isoflurane and sevoflurane on left ventricular function. C57BL/6 female mice were anesthetized with either isoflurane or sevoflurane at concentrations ranging from 0.5 to 5%. The cardiac function was assessed with transthoracic echocardiography (TTE). Sevoflurane caused a reduction of left ventricular function at lower concentrations compared with isoflurane. At concentrations of 2% and greater, sevoflurane significantly reduced cardiac output, ejection fraction, fractional shortening, and increased end-diastolic and end-systolic volumes. Isoflurane-induced reduction of left ventricular function was much less in magnitude when compared with sevoflurane. These data underscore the importance of using lower concentrations of volatile anesthetics during CPB especially during periods of cardiac recovery after aortic cross-clamp removal.

Peripheral vascular disease and serum phosphorus in hemodialysis: a nested case-control study.

BACKGROUND: Serum phosphorus (P) and the product of serum calcium x serum P (Ca x P), are frequently elevated in end-stage renal disease patients on maintenance hemodialysis (HD). Elevated P and Ca x P have been associated with vascular calcification in dialysis patients. OBJECTIVE: [corrected] To examine the role of P and Ca x P as risk factors for incident peripheral vascular disease (PVD) in HD patients with pre-existing CVD. METHODS: This nested case-control study is drawn from the 11 incident PVD events reported in the cohort of the Secondary prevention with antioxidants of cardiovascular disease in end-stage renal disease (SPACE): a randomized placebo-controlled trial. PVD was defined clinically and confirmed ultrasonographically. Each individual with a PVD event was matched for SPACE treatment group (vitamin E or placebo), age (in 4-year categories) and gender with two individuals who had no CVD end point during the follow-up period. RESULTS: Serum P and Ca x P levels were significantly higher in PVD patients than in controls. In univariate logistic regression analysis, only serum P predicted PVD in this population (OR 2.02, 95% CI 1.07 - 3.81, p = 0.03). In multivariate analysis, adjustment was made for variables dissimilar by PVD status including underlying renal disease, diabetes, smoking, history of angina pectoris, prescription for vitamin D3, erythropoietin, calcium channel blockers and aspirin. In this model, serum P remained the only significant predictor of incident PVD (OR 2.4, 95% CI 1.01 - 5.74, p = 0.04). CONCLUSIONS: Findings of the present study are consistent with a role for serum P and Ca x P in the pathogenesis of PVD in HD patients.

Pregnancy in membranous glomerulonephritis--course, treatment and outcome.

BACKGROUND: The effect and outcome of pregnancy in women with preexisting glomerulonephritis is a controversial issue. CASE: We report the clinical course and treatment of a 23-year-old pregnant woman with biopsy-proven membranous glomerulonephritis. When she conceived, the patient had been in stable remission for 1 year. In the 14th week of pregnancy, the patient developed uncontrolled hypertension and nephrotic syndrome. Daily 1 g methylprednisolone intravenous pulses were administered for 3 days, followed by a 4-week course of oral prednisone, 50 mg/day. Clinical improvement and normalization of arterial blood pressure were achieved. Oral prednisone 60 mg was administered on alternate days for another 4 weeks following 3 days of pulse therapy. At the end of treatment (26th gestational week), we observed a decrease of proteinuria (from 10.6-4.8 g/24 h) and rise in serum albumin (from 2.1-2.9 g/100 ml). At this time, blood pressure was 130/85. In the 34th week, a normal healthy male newborn was delivered by cesarean section. One year later she felt well, her blood pressure was 140/90, serum albumin was 3.4 g/100 ml, urine protein was 1.65 g/24 h and renal function was normal. The patient's child was healthy and well developed. CONCLUSION: Judicious use of a specific therapy to the underlying renal disease during pregnancy, together with a continuous supervision, can improve outcomes of these particular high-risk conditions.

Pamidronate-induced nephrotoxic tubular necrosis--a case report.

Few cases of pamidronate (bisphosphonate class of drugs) nephrotoxicity in humans have been previously reported in the literature. In 7 patients, the pamidronate-related nephrotoxicity was attributed to focal collapsing glomerulosclerosis [Markowitz et al. 2001], and in 1 patient was related to tubulo-interstitial inflammatory nephritis [Van Doom et al. 2001]. We report herein on a 65-year-old Caucasian female patient who presented with acute chronic renal failure due to pamidronate-induced toxic proximal tubular necrosis without immunologic or inflammatory tubulo-interstitial involvement. The acute pattern of renal failure resolved following cessation of pamidronate administration in this patient for osteoporosis; the patient also had a monoclonal gammopathy of unspecific origin (MGUS).

Secondary prevention with antioxidants of cardiovascular disease in endstage renal disease (SPACE): randomised placebo-controlled trial.

BACKGROUND: Excess cardiovascular mortality has been documented in chronic haemodialysis patients. Oxidative stress is greater in haemodialysis patients with prevalent cardiovascular disease than in those without, suggesting a role for oxidative stress in excess cardiovascular disease in haemodialysis. We investigated the effect of high-dose vitamin E supplementation on cardiovascular disease outcomes in haemodialysis patients with pre-existing cardiovascular disease. METHODS: Haemodialysis patients with pre-existing cardiovascular disease (n=196) aged 40-75 years at baseline from six dialysis centres were enrolled and randomised to receive 800 IU/day vitamin E or matching placebo. Patients were followed for a median 519 days. The primary endpoint was a composite variable consisting of: myocardial infarction (fatal and non-fatal), ischaemic stroke, peripheral vascular disease (excluding the arteriovenous fistula), and unstable angina. Secondary outcomes included each of the component outcomes, total mortality, and cardiovascular-disease mortality. FINDINGS: A total of 15 (16%) of the 97 patients assigned to vitamin E and 33 (33%) of the 99 patients assigned to placebo had a primary endpoint (relative risk 0.46 [95% CI 0.27-0.78], p=0.014). Five (5.1%) patients assigned to vitamin E and 17 (17.2%) patients assigned to placebo had myocardial infarction (0.3 [0.11-0.78], p=0.016). No significant differences in other secondary endpoints, cardiovascular disease, or total mortality were detected. INTERPRETATION: In haemodialysis patients with prevalent cardiovascular disease, supplementation with 800 IU/day vitamin E reduces composite cardiovascular disease endpoints and myocardial infarction.

Rectal colonization with vancomycin-resistant enterococci among high-risk patients in an Israeli hospital.

The prevalence of rectal carriage of vancomycin-resistant enterococci (VRE) in two high-risk populations--61 patients admitted to ICU and 92 patients on renal dialysis--was studied longitudinally over a period of six months in a 650-bed general hospital. ICU patients were swabbed weekly and dialysis patients monthly. Enterococcal isolates were fully identified using the ATB identification system, and MICs were determined according to the NCCLS recommendations. Enterococci were isolated in 52 (83.6%) ICU patients and 86 (93.4%) dialysis patients. VRE were recovered at least once in 14 (27%) ICU patients and four (4.8%) dialysis patients. All VRE isolates (MIC of vancomycin > or = 256 micrograms/mL) were resistant to teicoplanin (MIC > or = 32 micrograms/mL; vanA phenotype), 87.5% were ampicillin-resistant, and 92% showed high-level resistance to gentamicin; 88% were E. faecium. The main risk factors for acquisition of VRE included duration of hospitalization in the six months preceding entry into the study and during the survey (P = 0.009 and 0.007 respectively, for ICU patients), and duration of antibiotic administration (P = 0.005, for ICU patients). The impact of vancomycin was most prominent (P = 0.005 for receipt and 0.06 for duration of administration, in ICU patients). Six of the 18 VRE carriers developed bacteraemia, six isolates being vancomycin-susceptible and one vancomycin-resistant (one patient had both). In this study, the first in Israel, a low rectal carriage rate occurred in renal dialysis patients and antibiotic use was the most important risk factor for VRE colonization.

Serum malondialdehyde and prevalent cardiovascular disease in hemodialysis.

BACKGROUND: Oxidative stress has been proposed as a mechanism by which the accelerated rate of cardiovascular disease (CVD) observed in maintenance hemodialysis (HD) patients may be explained. This study examined the effects of HD and CVD on serum malondialdehyde (MDA) levels as a marker of oxidative stress in HD patients with and without prevalent CVD. Serum MDA levels and CVD prevalence in HD were modeled. METHODS: Serum MDA was determined using spectrophotometry in HD patients (N = 76, 53 men and 23 women, mean age 63.8 years) immediately prior to and at the conclusion of one midweek HD treatment. Traditional CVD risk factors, including serum lipids, lipoproteins, apolipoproteins, and fibrinogen, were also measured, as were serum chemistry and dialysis adequacy. RESULTS: Mean serum MDA levels were significantly elevated in HD patients with prevalent CVD compared with those without, whereas serum lipoprotein and plasma fibrinogen levels did not differ between the two groups. Patients in the highest compared with the lowest tertile of postdialysis MDA were nearly four times as likely to have prevalent CVD, and serum MDA was the single strongest predictor of prevalent CVD in this patient population. CONCLUSIONS: These findings indicate the presence of oxidative stress in HD patients, and are consistent with the theory of oxidative stress as a factor in accelerated CVD in this population.

Comparison of hemostatic factors and serum malondialdehyde as predictive factors for cardiovascular disease in hemodialysis patients.

Hemodialysis (HD) patients have accelerated cardiovascular morbidity and mortality rates compared with the general population. Identifying the factors that predict major coronary events in this population can direct the focus on prevention. This cross-sectional study compares known and suspected cardiovascular risk factors in HD patients with and without prevalent cardiovascular disease (CVD). In 76 HD patients (prevalent CVD, 44 of 76 patients), serum lipid, lipoprotein, apolipoprotein (Apo), plasma fibrinogen, tissue plasminogen activator (TPA), plasminogen activator inhibitor (PAI-1), and factor VII levels were measured using standard kits. Serum malondialdehyde (MDA; a marker of oxidative stress) was measured using spectrophotometry. Predictor variables were compared using analysis of variance and chi-squared tests, as appropriate. CVD prevalence was modeled using multiple logistic regression analysis, and odds ratios (OR) were calculated. Serum lipid, lipoprotein, Apo, plasma TPA, PAI-1, and factor VII values did not differ significantly from laboratory norms or discriminate for prevalent CVD in HD patients. Plasma fibrinogen levels were significantly elevated in HD patients compared with laboratory norms (369.4 +/- 130.02 v 276.7 +/- 77.7 mg/dL; P < 0.0001) but were not significantly different in HD patients with and without prevalent CVD. Serum MDA levels, both before and after the midweek HD treatment, were significantly elevated in all HD patients compared with laboratory norms (pretreatment, 2.6 +/- 0.8 nmol/mL; posttreatment, 2.1 +/- 0.3 v 0.91 +/- 0.09 nmol/mL; P < 0.01) and were significantly elevated in HD patients with prevalent CVD versus those without (pretreatment, 2.8 +/- 0.6 v 2.4 +/- 0.4 nmol/mL; P < 0.01; posttreatment, 2.3 +/- 0.4 v 1.94 +/- 0.2 nmol/mL; P < 0.01). Only serum MDA levels, both before and after the midweek treatment, contributed to the explanation of variation in CVD prevalence. OR for CVD in the highest versus lowest tertile of pretreatment MDA level was 2.71 (95% confidence interval [CI], 1.42 to 5.19). ORs for CVD in the highest versus lowest tertile of posttreatment MDA level was 3.65 (95% CI, 1.6 to 8.32).

The association between severe nephropathy and pheochromocytoma in the male F344 rat -- the National Toxicology Program experience.

The possible correlation between the severity of chronic progressive glomerulonephropathy (CPN) and the incidence of adrenal pheochromocytoma was examined in selected studies of male Fischer 344 (F344) rats at the National Toxicology Program (NTP). The NTP historical control database was first examined in order to determine whether there was association between the severity of CPN and the occurrence of adrenal pheochromocytoma in unexposed animals. Following this analysis, the 125 most recent NTP studies conducted in F344 rats were examined in order to determine how frequently chemicals that cause increased severity of CPN showed an increased incidence of pheochromocytoma. Finally, we examined the association between the incidence of pheochromocytoma and the severity of CPN in those NTP studies with chemically related increased rates of pheochromocytoma. In control male F344 rats surviving beyond 21 mo, the incidence of adrenal pheochromocytoma was consistently higher in animals with more severe CPN. This association was significant (p < 0.05) both for 900 NTP inhalation study controls and 900 NTP feeding study controls. An association was not consistently observed when dosed groups were considered. Although 22% (28/125) of NTP studies reported a chemically related increased severity of CPN, only 3 of these reported a corresponding significant increase in the incidence of pheochromocytoma. Of 6 NTP studies that reported increased incidence of pheochromocytoma, animals with pheochromocytoma from 5 of those studies had some degree of increased severity of CPN. However, the estimated strength of the correlation with the severity of CPN varied from study to study and was often quite different from that indicated by an analysis of the more extensive NTP control databases. The possible correlation between the severity of CPN and the incidence of pheochromocytoma may influence interpretation of carcinogenic effects observed at this site.

Salbutamol metered-dose inhaler with spacer for hyperkalemia: how fast? How safe?

OBJECTIVE: To determine the efficacy of inhaled salbutamol (rapidly delivered, using a metered-dose inhaler with a spacer device [MDI-S]) in lowering the serum potassium levels in patients with hyperkalemia. DESIGN: A randomized, double-blind, placebo-controlled trial. PATIENTS: Seventeen chronic renal failure patients referred to the Nephrology Unit between October 1, 1997 and March 31, 1998 for hemodialysis were randomized. INTERVENTION AND RESULTS: Group 1 received salbutamol followed by a placebo. Group 2 received a placebo followed by salbutamol. Each patient inhaled 1,200 microg salbutamol or a placebo through an MDI-S within 2 min. Blood samples were obtained repeatedly before inhalation and after 1, 3, 5, 10, and 60 min. The pulse rate and blood pressure were repeatedly measured. Insulin levels were examined in a subset of patients (n = 10) before, and 1 and 5 min following inhalation. Salbutamol's known side effects, palpitation, tachycardia tremor, and headache, were recorded. Potassium levels rose after 1 min following the completion of treatment and then decreased steadily thereafter. A rise of > or = 0.1 mEq/L was seen in 10 of 17 patients (59%) during the treatment period and there was no change (0%) seen during the placebo period (p < 0.0001). Within 3 min after inhalation of salbutamol, potassium levels declined as a function of time. Potassium levels in those patients taking the placebo did not change as a function of time (p < 0.001). The difference between the placebo and the salbutamol-treated periods reached significance after 5 min (p < 0.05). The serum glucose levels rose following inhalation of salbutamol, with a significant rise after 3 min. The heart rate rose significantly within the first 5 min following inhalation. Serum insulin levels remained unchanged 1 min after inhalation; however, after 5 min, a significant elevation was detected. CONCLUSION: Salbutamol inhalation of 1,200 microg, using an MDI-S, has a relatively rapid onset of action that induces a consistent reduction in serum potassium levels, starting 3 to 5 min following delivery. Unexpectedly, a paradoxical elevation was detected in serum potassium levels in the first minutes following inhalation. This effect, although minor (0.15 mEq/L above baseline), may cast some doubt on the role of salbutamol inhalation as the first treatment for excessive hyperkalemia.

Patterns of dietary intake and serum lipids interact with proteinuria as risk factors for progression of chronic renal failure.

UNLABELLED: This prospective study assessed the interactions between patterns of nutrient intake and serum lipids with other risk factors for progression of chronic renal failure. The study cohort consisted of 52 individuals with documented chronic renal failure, 18 women and 34 men, with a mean age of 65 +/- 11 years at the time of recruitment. The dependent variable was the rate of progression of chronic renal failure, which was determined by the slope of the curve generated from five or more values of the reciprocal of serum creatinine (SCr-1) and divided by time (in months of follow-up) for each patient, and recorded in dung/month. The independent variables included dietary factors (phosphorus, protein); serum lipids (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides); proteinuria; serum phosphorus; serum albumin; serum glucose; and blood pressure. Serum creatinine was drawn in a fasting state and determined using the picric acid technique on five or more occasions for each patient. The mean monthly rate of decline in dL/mg/month was calculated for each patient. The cohort was followed for 1.5 years. Descriptive statistics were determined for all variables. Analysis of principal components was used to generate variables representing patterns of nutrient intake and serum lipids. The outcome variable was modeled using stepwise linear regression which included principal components representing dietary and serum lipid patterns. The Student's t test and the F test were used for hypothesis testing. All tests were significant at p < 0.05. RESULTS AND CONCLUSIONS: Multicolinearity prevented the inclusion of more than one individual dietary or serum lipid variable into the multiple linear regression model of rate of decline in kidney function. Principal components representing patterns of dietary intake and serum lipids, contributed to the prediction of rate of decline in renal function together with proteinuria.

Regression equation predicts dietary phosphorus intake from estimate of dietary protein intake.

OBJECTIVE: To develop a predictive equation for dietary phosphorus intake. DESIGN: In this clinic-based, cross-sectional study, a dietitian-administered food frequency questionnaire provided dietary intake estimates for a population of patients with chronic renal failure. A prediction equation for dietary phosphorus intake was developed and was validated on another sample of patients with CRF from the same clinic. SUBJECTS: Outpatients treated for chronic renal failure at the E. Wolfson Medical Center Institute of Nephrology in Holon, Israel, participated in the study (N = 104, 73 men and 31 women, mean age = 65.6 years). The validation sample consisted of 53 outpatients with chronic renal failure (38 men and 15 women, mean age = 64.2 years) from the same clinic. MAIN OUTCOME MEASURES: Dietary variables (ie, energy, protein, carbohydrate, fat, phosphorus) were examined in terms of crude intake, as percentage of total energy intake, and per kilogram of body weight. STATISTICAL ANALYSES PERFORMED: Stepwise linear regression analysis and Student's t tests were used to examine relationships between dietary phosphorus and other variables. RESULTS: Dietary phosphorus (milligrams) = 128 + 14 (protein intake [grams]) was the best-fitting equation and explained 84% of the variance in dietary phosphorus intake. APPLICATIONS: The prediction equation for dietary phosphorus intake is especially useful for renal dietitians who calculate patient diets by hand.

Increased urinary trypsin-inhibitory activity in mercuric chloride induced nephrotoxicity in Wistar rats.

UNLABELLED: The relationship between trypsin-inhibitory activity (TIA) and the nephrotoxic effects of mercuric chloride (HgCl2)--as illustrated by proteinuria and by a drop in the glomerular filtration rate (GFR) measured by creatinine clearance test (CCT)--was investigated in Wistar rats. HgCl2, 150 or 250 micrograms/100 g BW per day was injected intraperitoneally three times a week for 2 weeks. Both groups showed a significant degree of proteinuria and urinary TIA. Group B (250 micrograms HgCl2/100 g BW) displayed a greater drop in GFR than group A (150 micrograms HgCl2/100 g BW). The urinary TIA was significantly correlated with proteinuria (group A: r = 0.87, group B: r = 0.84), but it was also significantly inversely correlated with the CCT (A: r = -0.96; B: r = -0.88). IN CONCLUSION: these results suggest that increased urinary TIA may be involved in and indicative of the pathogenesis of mercuric chloride induced nephrotoxicity.

Carnitine palmitoyltransferase deficiency: an underdiagnosed condition?

Two apparently healthy adults were admitted because of acute muscle cramps, severe weakness, and red urine excretion. Patient No. 1 developed the symptoms following intense exercise and patient No. 2 during a febrile infection. Both of them experienced such episodes in the past, but these were medically misinterpreted. Their present manifestations were accompanied by renal failure which subsided gradually and was found to be a result of rhabdomyolsis and myoglobinuria. Further investigations yielded a deficiency of carnitine palmitoyltransferase as a background to the acute muscular destruction. Examination of a sister of patient No. 2 who had a similar past history revealed the same metabolic disorder. Carnitine palmitoyltransferase deficiency, as a cause of nontraumatic rhabdomyolysis, is a distinct entity in the pathogenesis of acute renal failure. Our experience (3 patients within 2 years) makes us presume that this condition is not as rare as hitherto reported and should rather be considered in cases of 'nonhematuric' red urine and acute renal failure.

[Acute renal failure as a complication of cholera].

We present a 72-year-old man who had episodes of severe, acute renal failure during severe attacks of diarrhea caused by Vibrio cholerae. Patterns of acute tubular necrosis and tubulointerstitial nephritis developed following hypotension and decrease in renal blood flow, causing secondary renal ischemia. There was severe dehydration with profound hypovolemia and infection. The clinical picture included fever, weakness, arthralgia, pedal edema, mild bilateral pleural effusions, anemia, leukocytosis, azotemia with a maximum of 330 mg/dl of urea, creatine to a maximum of 9.8 mg/dl, hypoproteinemia, severe metabolic acidosis, marked increase in lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), microscopic hematuria, sterile leukocyturia, normoglycemic glucosuria and phosphaturia with diminished tubular reabsorption of phosphorus. A short oliguric phase was followed by a polyuric phase lasting about 10 days, and glomerular and tubular function became normal after about 3 weeks. Treatment was by intensive infusions of fluids, electrolytes, sodium bicarbonate, salt-free albumin and antibiotics. To the best of our knowledge, this renal complication of cholera has not yet been described in Israel.

Presence of human papilloma virus in transitional cell carcinoma in Jewish population in Israel.

The possible causal association of human papilloma virus (HPV) with transitional cell carcinoma (TCC) of the urinary bladder in Israeli Jewish patients was assessed. One hundred and ten histopathological TCC sections were examined by peroxidase anti-peroxidase (PAP) method. HPV capsid antigen was demonstrated in 19 out of 110 cases (17.3%). HPV-DNA sequences, determined by in situ DNA-DNA hybridization at high stringency wash were present in 24 cases (21.8%): 16(14.5%) cases proved to be HPV6/11 and 8 (7.3%) were HPV 16/18 positive. Four (3.6%) of the HPV 6/11 positive specimens cross hybridized with HPV 31/33/35 at low stringency conditions. Sixteen samples known to be positive by in situ hybridization were reconfirmed by polymerase chain reaction (PCR). When the PCR was performed on the 43 negative cases, an additional 4(9.3%) HPV positive cases were revealed: two proved to be HPV 6/11 and two HPV 16/18. Comparison of the different methods for HPV detection in 59 TCC histopathological samples, showed good correlation; an overall positivity of 33.9% by PCR, 27.1% by in situ hybridization and 25.4% by PAP was observed. Forty one samples from nontumoral material of the bladder or post mortem specimens served as controls and 4.8% HPV DNA was present in only two cases: one HPV 6/11 and one 16/18. Hence, HPV in TCC of the bladder is detected at a relatively high frequency and might be involved in the pathogenesis of this tumor among Jewish population in Israel.