Inerting of magnesium dust cloud with Ar, N2 and CO2.

Experiments were conducted on the inerting of magnesium dust with N(2), CO(2), and Ar. Comparing the maximum explosion pressure, maximum rate of pressure rise, and limiting oxygen concentration with different inertants, it was determined that Ar is not the best inert gas under all conditions as commonly believed. N(2) was more effective than Ar as an inertant. CO(2) provided more inerting effect than either Ar and N(2) in low magnesium dust concentrations, although explosibility was increased at higher dust concentrations. Both N(2) and CO(2) as inerting agents showed higher LOC values than Ar. These results indicated that N(2) is a more economical inerting gas than Ar for the tested coarse magnesium dust.

Myelodysplastic syndromes: the role of flow cytometry in diagnosis and prognosis.

Flow cytometric immunophenotypic analysis is a well-recognized and widely accepted adjuvant test to increase the sensitivity and specificity of diagnosis in potential myelodysplastic syndrome (MDS) cases. In addition, flow cytometric analysis provides prognostic information in MDS that is not available from other sources. The flow cytometric findings indicative of MDS and its value is a diagnostic adjunct are discussed.

Influence of race on kidney transplantation in the Department of Defense healthcare system.

BACKGROUND: We report the influence of race on transplant outcomes in the Department of Defense (DOD) system. METHODS: Retrospective cohort analysis of all kidney transplants performed at WRAMC from 1996 to 2005. Kaplan-Meier analysis was used to assess for differences in graft survival, and Cox regression was used to calculate adjusted hazard ratios for graft loss. For our analyses, we used the cutoff of 6 years (year 2000) when we introduced thymoglobulin induction; maintenance immunosuppression consisted of mycophenolate mofetil and tacrolimus, and rapid steroid taper (completed withdrawal at 6 weeks) was used for all patients. RESULTS: There were 220 transplants (91 Blacks, 107 Caucasians and 22 Asians). Because the curve for graft survival for Blacks over time violated the proportional hazards assumption (at 6 years post-transplant), analysis was segregated into two segments. Through 6 years of follow-up, graft survival was 77% for Blacks and 81% for non-Blacks (p = 0.74 by log rank). Through 9 potential years of follow-up, graft survival for Blacks was 56% and 78% for Whites (p = 0.005). In Cox regression analysis, Black race, compared with non-Black race, was not significantly associated with graft loss at 6 years, but was significantly associated with graft loss occurring after 6 years. CONCLUSIONS: In the DOD health system, no significant differences were seen in graft survival among recipients of different races at 6 years. Black recipients who received a kidney transplant before the year 2000 showed decreased graft survival compared to non-Blacks. This was consistent with change in immunosuppressive regimen in our institution with the introduction of thymoglobulin induction and maintenance therapy with tacrolimus, mycophenolate mofetil and withdrawal of prednisone at 6 weeks.

Hospitalized valvular heart disease in patients on renal transplant waiting list: incidence, clinical correlates and outcomes.

BACKGROUND: Patients with ESRD are at increased risk for heart valve calcification. It has not been established whether hospitalized valvular heart disease (VHD) is a substantial barrier to renal transplantation (RT) after transplant listing, or whether VHD progresses after RT. METHODS: Using data from the USRDS, we studied 35,215 patients with ESRD enrolled on the renal transplant waiting list from July 1994 to June 1997. Cox non-proportional hazards regression models were used to calculate adjusted, time-dependent hazard ratios (HR) for RT and VHD. RESULTS: In comparison to maintenance dialysis (2.2/1,000 person years), RT was independently associated with a lower hazard for hospitalization for VHD (0.7/1,000 person years, HR 0.28, 95% confidence interval 0.17 - 0.47). Renal transplant recipients had much lower rates of VHD after transplant than before (rate ratio (RR) 0.49, 95% Cl 0.47 - 0.52). Patients with VHD were significantly less likely to receive RT (adjusted rate for RT 0.38, 95% CI 0.20 - 0.45) but patients who received valve replacement surgeries (VRS) were not affected (adjusted rate for RT 1.10, 95% CI 0.52 - 2.32, not significant). CONCLUSIONS: VHD is an uncommon but serious barrier to RT after listing, while VRS is not a significant barrier to RT. Established VHD does not appear to worsen after RT. Clinicians should consider giving increased attention to the detection and treatment of VHD during the pre-transplant evaluation.

The impact of renal transplantation on the incidence of congestive heart failure in patients with end-stage renal disease due to diabetes.

BACKGROUND: Patients with end stage renal disease (ESRD) are at increased risk for cardiovascular disease. We hypothesized that the clinical incidence of congestive heart failure (CHF) would be lessened after successful renal transplantation, as many of the metabolic and intravascular volume abnormalities associated with dialysis-dependent ESRD would resolve. METHODS: Using data from the USRDS, we studied 11,369 patients with ESRD due to diabetes enrolled on the renal and renal-pancreas transplant waiting list from 1 July 1994-30 June 1997. Cox non-proportional hazards regression models were used to calculate adjusted, time-dependent hazard ratios (HR) for time to the most recent hospitalization for CHF (including acute myocardial infarction, unstable angina, or other CHF, ICD9 Code 428.x) for a given patient in the study period, controlling for both demographics and comorbidities in the medical evidence form (HCFA 2728). RESULTS: In comparison to maintenance dialysis, renal transplantation was independently associated with a lower risk for CHF (HR 0.64, 95% confidence interval, 0.54-0.77) in a model including age, gender, race, and year of first dialysis, but not in a model including comorbidities from the medical evidence form, although the sample was much smaller. CONCLUSIONS: Patients with ESRD due to diabetes on the renal transplant waiting list were much less likely to be hospitalized for congestive heart failure after renal transplantation, despite post transplant complications due to immunosuppression.

Analyzing process variation in chart review using a networked spreadsheet application in the Walter Reed Army Medical Center Nephrology Clinic.

The role of reviewer variation in interpreting outcomes of outpatient clinic chart reviews has been poorly studied. The present study used results collected from a network-based spreadsheet application (Microsoft Excel), which is widely available throughout the Army Medical Department, for chart reviews. Data were collected from January 1998 to August 2000, and 2,308 charts of 1,127 patients were reviewed. Results showed a significant improvement in documentation of contact with the referring provider from 1998 to 2000 (55.9% in 1998, 81.6% in 1999, and 80.6% in 2000; p < 0.01 by chi 2 for both). The percentage of charts for new consultations with inadequately controlled blood pressure managed appropriately improved from 73.7% in 1999 to 89.2% in 2000 (p < 0.01 by chi 2). These results persisted in logistic regression analysis controlling for different reviewers. In conclusion, widely available office automation tools allow the systematic analysis of chart review data with the potential to improve practice patterns.

Effects of angiotensin-converting enzyme inhibitor and steroid therapy on proteinuria in FSGS: a retrospective study in a single clinic.

We retrospectively evaluated the response to steroids (S) +/- angioten-sin-converting enzyme inhibitors (ACEI) vs. ACEI in nephrotic patients with FSGS seen in our clinic from 1992 - 1999. Of 48 patients with biopsy-proven FSGS, 30 had pre-therapy and follow-up evaluations of proteinuria. Of these, 22 were nephrotic (> or = 3 g protein/24 h). Twelve/22 were treated with S and 10/22 with ACEI +/- HMG-CoA reductase inhibitor (statin) alone. 92% of S patients received ACEI during follow-up, 83% concurrently with steroid treatment. The two cohorts (S vs. ACEI) were not different in age (34 +/- 12 vs. 33 +/- 12), sex (75% vs. 78% male), or ethnicity (83% vs. 83% African American). Mean follow-up time was 16 (range 4 - 61 months) vs. 23 months (range 6 - 56 months). Mean S dose was 70 mg qd (range 60 - 100 mg), with mean treatment duration of 4 months. Nephrotic patients were compared with regard to degree of proteinuria at follow-up. There were no complete remissions (proteinuria < or = 200 mg/24 h) in either group. There was no difference in partial remissions (> 200 mg to < 3 g proteinuria/24 h) between the two groups - 5/12 vs. 6/10 (p = 0.434). There was no difference in the proportion of patients progressing to ESRD. Although proteinuria decreased significantly with time in both groups, there was no significant treatment effect. There was no significant time or treatment effect on serum creatinine. Mean arterial pressure and serum cholesterol were not significantly different between the groups. Thus, treatment with S +/- ACEI is no more effective in reducing proteinuria in FSGS than treatment with ACEI alone.

The impact of bleeding times on major complication rates after percutaneous real-time ultrasound-guided renal biopsies.

BACKGROUND: Previous studies have shown that bleeding times have positive predictive values of only 5% for perioperative bleeding in unselected populations. Nevertheless, performing bleeding times prior to all renal biopsies is common in nephrology practice. METHODS: We report complications of 112 renal biopsies done at Walter Reed Army Medical Center (WRAMC) from 1996-99 performed without preceding bleeding times. Renal biopsies were done only on normotensive (<140/90) patients who had not recently been taking aspirin or non-steroidal anti-inflammatory agents, under real-time ultrasound guidance with automated 16 g (WRAMC) spring-loaded guns. High-risk patients (with serum creatinine > or = 3 mg/dl or creatinine clearance < or =30 cc/min by Cockroft-Gault formula, N=18, 16%) at WRAMC were treated with pre-renal biopsy estrogens or DDAVP. Factors were tested for their association with complications after renal biopsy using Chi Square testing for categorical variables and student's t-test for continuous variables. A stepwise logistic regression model was used to test for independent significance of factors. RESULTS: There were two cases each of gross hematuria and inadequate tissue (1.8% each). There were no transfusions or deaths. In univariate analysis, male gender and lower serum creatinine level at time of biopsy were significantly associated with increased risk of complications after biopsy. However, these factors were not significant in logistic regression analysis. CONCLUSION: This study suggests that the use of bleeding times does not significantly alter the major complication rates associated with percutaneous real-time ultrasound guided renal biopsy.

Renal biopsy in high-risk patients with medical diseases of the kidney.

The number of high-risk patients undergoing renal biopsy is likely to increase in the near future because of the increased use of anticoagulants for such conditions as atrial fibrillation, combined liver and kidney disease caused by hepatitis C, and the aging of the population. Nephrologists need to become increasingly familiar with evaluating such patients through both specialized management of percutaneous kidney biopsy and alternate methods of renal biopsy, which primarily consist of open (surgical) biopsy, transjugular (transvenous) biopsy, and laparoscopic biopsy. The indications, complications, and general approach to such patients are discussed. This is a US government work. There are no restrictions on its use.

Life expectancy benefits of cancer screening in the end-stage renal disease population.

Health maintenance includes secondary prevention through cancer screening. There are no established guidelines for cancer screening patients with end-stage renal disease (ESRD). Using an established method of estimating life expectancy, published literature on cancer screening, and information from databases on mortality and malignancy (US Renal Data System 1997 Annual Data Report and the SEER Cancer and Statistical Review, 1973-1994), a "real-time life expectancy calculator" was developed to guide the primary help provider in making informed decisions on the benefits of cancer screening in individual patients. Potential days of life saved by each screening method can be calculated using the difference in life expectancy per the DEALE (declining exponential approximation of life expectancy) method with and without cancer screening. Using two sets of assumptions (one to enhance any bias toward support for screening and one to limit this bias), a range of potential days of life saved with screening for breast and colon cancer can be calculated in individual patients with ESRD. In breast cancer, for example, a 50-year-old black woman with ESRD and multiple risk factors would have 41 to 291 potential days of life saved with screening. A 60-year-old white woman with ESRD and diabetes mellitus (DM) would have only 1 to 16 days of life saved. This life expectancy calculator can guide the primary health care provider in making clinical decisions concerning screening in the ESRD population. In addition to assisting in patient education, the calculator can be updated as new information becomes available regarding relative risk, treatment, and mortality.

Lack of a phenotype in transgenic mice aberrantly expressing COL2A1 mRNA because of highly selective post-transcriptional down-regulation.

We reported previously that a 1.9-kb 5'-fragment from the human COL1A1 gene drove transcription of a promoterless human COL2A1 gene in tissues of transgenic mice that normally express the COL1A1 but not the COL2A1 gene. In the present study, we have established that the aberrant transcription of the COL2A1 gene did not produce any gross or microscopic phenotype, because the transcripts were not efficiently translated in cells that do not normally express the COL2A1 gene. In two lines of transgenic mice, the mRNA levels from the transgene were 30% to 45% of the mRNA for the proalpha1(I) chain of type I procollagen, the most abundant mRNA in the same tissues. Analysis of collagens extracted from skin of the transgenic mice indicated that triple-helical type II collagen, with the normal pattern of cyanogen bromide peptides, was synthesized from the transgene. However, the level of type II collagen in skin was less than 2% of the level of type I collagen. Hybridization in situ indicated the presence of mRNA for both COL2A1 and COL1A1 in the same cells. Immunofluorescence staining for type II collagen, however, was negative in the same tissues. The results, therefore, indicated that many mesenchymal cells in the transgenic mice had high steady-state levels of the homologous mRNAs for type I and type II procollagen, but only the mRNAs for type I procollagen were efficiently translated.

Review of thrombotic thrombocytopenic purpura in the setting of systemic lupus erythematosus.

OBJECTIVE: Thrombotic thrombocytopenic purpura (TTP) has been described in association with systemic lupus erythematosus (SLE) rarely. The diagnosis of TTP as a process separate from SLE may be difficult because both share similar features, including thrombotic microangiopathy. METHODS: A case is described of the simultaneous occurrence of TTP and SLE. The clinical, laboratory, and histologic findings of the patient are reported. The association of TTP and SLE in the literature is analyzed. We review separately the pathogenesis, role of antiphospholipid antibodies, and the differential diagnosis of TTP complicating the course of SLE. RESULTS: Forty cases of TTP in association with SLE are reported in the world literature. Three distinct groups were defined by the presentation of TTP that occurred subsequent to, before, or simultaneous with SLE (groups 1, 2, and 3, respectively). Renal biopsy in a patient with lupus nephritis may reveal thrombotic microangiopathy, which may be seen independently or represent a concomitant systemic thrombotic process such as TTP, disseminated intravascular coagulation, or antiphospholipid antibody syndrome. CONCLUSION: TTP in association with SLE is rare, and the diagnosis may be challenging. Although the etiology of TTP remains elusive, certain autoimmune mechanisms, platelet abnormalities, and fibrinolytic disorders may be shared with SLE and provide the basis for their association. Management requires timely diagnosis and aggressive treatment by therapeutic plasma exchange.

Effect of glycine on cisplatin nephrotoxicity and heat-shock protein 70 expression in the rat kidney.

Glycine has been shown to protect against cisplatin (CP) nephrotoxicity in rats and to enhance the in vitro expression of heat-shock protein (hsp) 70 in renal epithelial cells following sublethal heat shock. We hypothesized that the protective effect of glycine against CP nephrotoxicity may be due to an up-regulation of Hsp 70 protein expression. Male Sprague-Dawley rats were divided into 4 treatment groups based upon infusion of glycine and injection of CP or their respective vehicles. At 5 days after treatment animals administered CP alone demonstrated a significant decrease in creatinine clearance compared to baseline (0.77 +/- 0.32 mL/min vs. 3.90 +/- 0.87 mL/min, p < 0.05). Treatment with glycine and CP attenuated this response, with no significant decline seen in creatinine clearance at day 5 compared to baseline (2.25 +/- 0.31 mL/min vs. 3.40 +/- 0.86 mL/min). Semiquantitative histological study revealed a marked decrease in proximal tubular injury at the juxtamedullary and outer medullary regions among animals treated with glycine and CP compared to those animals treated with CP alone. There were no differences in renal cortical and medullary Hsp 70 levels by Western immunoblotting between animals treated with glycine and CP compared to CP alone at 4 h and 5 days after treatment. Immunohistochemical studies of animals treated with CP alone revealed the diffuse presence of Hsp 70 in the cytoplasm of injured and necrotic proximal tubular cells 5 days after treatment. Animals receiving CP and glycine demonstrated a more focal presence of Hsp 70 restricted to injured proximal tubular cells, with no staining of uninjured cells. The protective effect of glycine in CP-induced acute and renal failure in the rat does not appear to be associated with enhancement of Hsp 70 expression.

Distribution of the cellular uptake of phosphorothioate oligodeoxynucleotides in the rat kidney in vivo.

Previous animal studies have demonstrated that following systemic administration phosphorothioate oligodeoxynucleotides (S-ODNs) are primarily excreted by the kidneys and that renal tissue levels of S-ODNs exceed that of other organs. Thus, the kidney may be an ideal target organ for application of antisense S-ODNs in vivo. We examined which cells within the rat kidney have uptake of radiolabeled S-ODNs following intravenous infusion. A 20-base 35S-ODN was infused into 6 adult male Wistar rats. Three animals each were sacrificed 30 min and 4 h after infusion. The kidneys were then removed, fixed, and tissue autoradiography was performed. Similar results were obtained in both groups. The highest level of radioactivity was seen within the proximal tubules. Lower levels of activity were seen within the glomerulus, the parietal epithelial cells of Bowman's space, and distal tubular cells. Very weak activity was also detected within the cells of the loop of Henle and the medullary collecting ducts. These results demonstrated that within the kidney S-ODNs were taken up primarily by proximal tubular cells, with much lower uptake by cells in other segments of the nephron.

Sublethal heat shock and cyclosporine exposure produce tolerance against subsequent cyclosporine toxicity.

Sublethal heat shock has been shown to produce tolerance in cells and tissues subsequently exposed to heat or ischemia/ATP depletion. We tested whether heating LLC-PK1 cells for 2 h at 42 degrees C induced heat shock protein-70 (HSP-70) gene expression and conferred tolerance against subsequent cyclosporine A (CyA) toxicity. HSP-70 mRNA was increased immediately after heat shock, returning to baseline by 4 h. HSP-70 protein increased by 1 h after heat shock and declined thereafter, approaching baseline after 72 h. Cells heat shocked at 4 and 24 h prior to CyA exposure were significantly more viable than controls, at CyA concentrations near the median lethal dose (LD50). Cytoprotection declined with time after heat shock, concurrent with declining HSP-70 protein levels. Sublethal CyA exposure (50 micrograms/ml) for 24 h produced upregulation of HSP-70 mRNA and protein. Pretreatment with 50 micrograms/ml CyA for 24 h followed by exposure to a toxic concentration of CyA (200 micrograms/ml) produced significant cytoprotection compared with untreated controls. In conclusion, HSP-70 protein induction by sublethal heat shock or CyA exposure was associated with tolerance against subsequent lethal CyA exposure.

Effect of administration of insulin on streptozotocin-induced diabetic hypertension in rat.

We have reported that streptozotocin-induced insulin-dependent diabetes mellitus in 25% reduced renal mass rats is associated with low-renin, volume-expanded hypertension and that the development of the hypertension can be prevented with insulin. In this study we examined the effect of insulin after the animals had developed sustained hypertension. Normotensive 25% reduced renal mass rats were treated with streptozotocin and, as expected, developed insulin-dependent diabetes mellitus and hypertension. After 4 weeks of sustained hypertension, neutral protamine Hagedorn insulin (6 to 8 IU/d) was administered subcutaneously for 4 weeks. As expected, insulin treatment decreased plasma glucose and increased body weight gain relative to untreated diabetic rats. On the other hand, insulin treatment did not reverse the hypertension and albuminuria. It also did not normalize extracellular fluid volume and plasma renin activity. Furthermore, insulin treatment did not reverse the increase in plasma Na+,K(+)-ATPase inhibitory activity (determined by both radioimmunoassay and bioassay) and the inhibition of myocardial microsomal Na+,K(+)-ATPase activity observed in the untreated diabetic hypertensive rats. 5'-Nucleotidase, a membrane marker, was not different between insulin-treated and untreated diabetic rats. These results show that insulin, given as here described, does not reverse the insulin-dependent diabetes mellitus hypertension in 25% reduced renal mass rats once it is established, perhaps because it does not reverse the albuminuria, volume expansion, increase in endogenous digitalis-like substance, and inhibition of cardiovascular muscle cell Na+,K(+)-ATPase activity.

Chronic blood pressure effects of bufalin, a sodium-potassium ATPase inhibitor, in rats.

Endogenous Na+,K(+)-ATPase inhibitors may have a role in the mechanism of low-renin hypertension. Two such compounds have been characterized: ouabain from human plasma and resibufogenin from toad plasma. Previously, we examined the acute effects of ouabain and bufalin (which has the same structure as resibufogenin except for one H+) in normal rats. Bufalin raised blood pressure, but ouabain had little effect. In contrast, given chronically, ouabain substantially increased blood pressure in normal rats and 70% reduced renal mass rats on a salt-free diet. We have now examined the chronic effects of bufalin in rats. Normal rats received 14.8 micrograms/kg per day bufalin or an equimolar dose of ouabain intraperitoneally for 6 weeks; 70% reduced renal mass rats also received 14.8 micrograms/kg per day bufalin. Another group of normal rats received 29.6 micrograms/kg per day bufalin intraperitoneally for 6 weeks. Respective control animals received vehicle. In contrast to ouabain, blood pressure did not increase in normal rats receiving the 14.8 micrograms dose of bufalin. However, normal rats receiving 29.6 micrograms bufalin and 70% reduced renal mass rats receiving 14.8 micrograms bufalin developed significant increases in blood pressure. Increases in blood pressure were associated with decreases in myocardial Na+,K(+)-ATPase activity and correlated with increased plasma Na+,K(+)-ATPase inhibitory activity. Thus, although bufalin is a more potent pressor agent than ouabain when both agents are given acutely, ouabain is at least as potent a vasopressor agent as bufalin when given chronically. Thus, both are pressor agents, more so in the presence of reduced renal mass, when given chronically in the rat.

Long-term ouabain administration produces hypertension in rats.

Ouabain has recently been identified as an endogenous Na(+)-K+ pump inhibitor. We administered ouabain chronically to normotensive rats with varying degrees of reduced renal mass (RRM) and to normal two-kidney rats to see whether hypertension could be produced. Normal male Wistar rats and rats with 25%, 60%, and 70% RRM received ouabain (13.9 micrograms/kg per day IP) in normal saline for 4 weeks followed by ouabain (27.8 micrograms/kg per day IP) for 3 to 4 more weeks. Respective control animals received vehicle only. Blood pressure was recorded weekly by tail plethysmography. Animals received tap water and standard rat chow, except for 70% RRM rats, which received distilled water and sodium-free chow. After 6 to 8 weeks of treatment, with rats under thiobutabarbital anesthesia, direct blood pressure was determined. Plasma, tissue, and urinary ouabain levels were measured with a specific radioimmunoassay. Animals receiving ouabain developed significant increases in mean blood pressure compared with control animals (70% RRM, 147 +/- 4 vs 116 +/- 4 mm Hg; 60% RRM, 140 +/- 4 vs 107 +/- 3 mm Hg; 25% RRM, 131 +/- 5 vs 100 +/- 2 mm Hg; no RRM, 116 +/- 4 vs 98 +/- 5 mm Hg). Plasma ouabain levels measured 24 hours after the last ouabain dose were not different in animals receiving ouabain vs those receiving vehicle. However, kidney tissue ouabain levels were significantly greater (6.39 +/- 1.17 vs 2.36 +/- 0.52 micrograms/kg, P < .05) in animals receiving ouabain. In conclusion, ouabain, given chronically, is associated with the development of hypertension in RRM rats as well as in normal rats. Blood pressure was greater in animals with greater degrees of RRM for a given ouabain dose.