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Biomedical subjects

R L Mehta

Publications and source records attributed to R L Mehta.

At least 37 records · Page 2Linked to original sources

Assessment of dry weight in hemodialysis: an overview.

Fluid balance is an integral component of hemodialysis treatments to prevent under- or overhydration, both of which have been demonstrated to have significant effects on intradialytic morbidity and long-term cardiovascular complications. Fluid removal is usually achieved by ultrafiltration to achieve a clinically derived value for "dry weight." Unfortunately, there is no standard measure of dry weight and as a consequence it is difficult to ascertain adequacy of fluid removal for an individual patient. Additionally, there is a lack of information on the effect of ultrafiltration on fluid shifts in the extracellular and intracellular fluid spaces. It is evident that a better understanding of both interdialytic fluid status and fluid changes during hemodialysis is required to develop a precise measure of fluid balance. This article describes the current status of dry weight estimation and reviews emerging techniques for evaluation of fluid shifts. Additionally, it explores the need for a marker of adequacy for fluid removal.

Biomarkers↗

Acute renal failure in the 21st century: recommendations for management and outcomes assessment.

Acute renal failure (ARF) remains a common and potentially devastating disorder affecting as many of 5% of all hospitalized patients, with a higher prevalence in patients in critical care units. ARF is more frequently observed in the setting of multiorgan dysfunction syndrome (MODS) and in elderly patients with complex disease, where mortality is high. Numerous technical advances have not yet impacted favorably on this high mortality rate. This report summarizes recommendations from participants at the National Institutes of Health Conference: "Acute Renal Failure in the 21st Century," May 6 to 8, 1996, in Bethesda, MD. The focus is on categorizing recent clinically relevant developments in the field and on identification of new research initiatives to transfer a new body of knowledge derived from fundamental studies and laboratory investigation to the management of ARF in the new millennium. The development of a multicenter database through cooperative multicenter studies is advocated. Future studies should define the appropriate outcome measures to assess and emphasize the impact of hemodynamic monitoring, adjunctive agents, and adequacy and modality of renal replacement therapy on outcomes in ARF.

Acute Kidney Injury↗

Continuous renal replacement therapies in the acute renal failure setting: current concepts.

Several new methods of renal replacement therapy are now available for the treatment of acute renal failure in the intensive care unit (ICU) setting. Continuous dialysis techniques have evolved over the last decade and are now increasingly used in the ICU. This review provides a framework for the evaluation of these therapies and discusses the emerging indications for their use.

Acute Kidney Injury↗

Synthetic peptides of human CD4 enhance binding of immunoglobulins to monocyte/macrophage cells. II. Mechanisms of enhancement.

We have previously shown that a synthetic peptide corresponding to amino acid residues 21-49 of the first extracellular domain of human CD4 binds immunoglobulins (Ig) and antibody: antigen (Ab:Ag) complexes, and greatly enhances the uptake of aggregated Ig by monocyte/macrophage U937 cells. In this report, we investigated the mechanisms of enhanced uptake, and the contribution of different receptors present on the surface of monocyte/macrophage cells to this phenomenon. Our results indicate that both Fc receptor (FcR) and cell surface CD4 participate in the enhanced uptake of Ig promoted by the synthetic peptide of CD4. The involvement of these two receptors was demonstrated in experiments using monoclonal antibodies to FcR and CD4, as well as monosialoganglioside GM1, a substance known to modulate surface CD4. The participation of CD4 was further confirmed using the CD4 monocyte/macrophage cell line MM-6. Together, the results of these experiments indicate that surface CD4 may cooperate with FcR in handling aggregated Ig and Ab:Ag complexes. The implications of these findings for immunoregulation by Ab:Ag and idiotype:anti-idiotype (Id:anti-Id) complexes, and infection of macrophages by HIV, are discussed.

Antigen-Antibody Complex↗

Mathematical formulation to help identify the patient at risk of ischemic tissue necrosis--a potentially lethal complication of chronic renal failure.

Ischemic tissue necrosis (ITN) has been described as a complication of hyperparathyroidism (HPT) in patients with end-stage renal disease (ESRD) and is associated with a mortality rate of up to 80%. Early recognition of ITN is important but difficult. Optimal treatment is controversial. Based on an analysis of the English literature and a recent clinical experience, a mathematical expression to aid in the identification of high-risk patients (2 x [CaPO(4) - 5] x alkaline phosphatase x PTH ratio) was developed. The values for this expression were calculated in 3 recently reported cases and our case (n = 4). The values were compared with those of a group of 54 hyperparathyroid chronic hemodialysis patients (controls); the mean values were significantly different (p < 0.001). The expression, consisting of 4 easily measured laboratory values, appears to differentiate patients with this complication of ITN from patients with only severe HPT. Ten new additional cases were evaluated using the equation; the sensitivity of the equation was 80% and the specificity 92%, positive predictive value was 66% and the negative predictive value 96%. Long-term validation of this equation is required but it appears to be discriminatory and, thus, promising, given the potentially lethal consequences of ITN.

Adult↗

Identification of novel heparin-releasable proteins, as well as the cytokines midkine and pleiotrophin, in human postheparin plasma.

The heparin-releasable proteins are a group of proteins that are targeted to the endothelial surface by attachment to glycosaminoglycans and may have functions specific to the endothelium-blood interface. In this study, heparin-affinity chromatography of human postheparin plasma was used as a method to identify and study novel heparin-releasable proteins. Six proteins seen on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels have increased levels in plasma after intravenous heparin. The six proteins are platelet factor 4, midkine, pleiotrophin, and several novel proteins. Midkine and pleiotrophin are related cytokines that are developmentally regulated, neurotrophic, and mitogenic. Additional studies show that levels of midkine and pleiotrophin peak at 10 to 30 minutes after injection of heparin. Heparin-releasable midkine and pleiotrophin do not originate from blood cells or the kidney. Heparin-releasable midkine may originate from endothelial cells. Soft agar culture of an adenocarcinoma cell line (SW-13) demonstrates growth-stimulating activity similar to that described for pleiotrophin in the heparin-agarose eluate of postheparin plasma but not in the heparin-agarose eluate of preheparin plasma. It is concluded there are more heparin-releasable proteins than previously identified, including midkine and pleiotrophin, and that heparin-affinity chromatography of postheparin plasma is a useful technique for identifying novel heparin-releasable proteins.

Amino Acid Sequence↗

Extracorporeal management of acute renal failure patients at high risk of bleeding.

The incidence of systemic bleeding events and extracorporeal clotting was studied in 57 critically ill acute renal failure patients treated with intermittent hemodialysis (IHD) and/or continuous arteriovenous hemodialysis (CAVHD), using heparin (Hep), saline-flush (Sal, no anticoagulant), and citrate (Cit) anticoagulation protocols. Thirty-seven patients received a single dialysis modality, and 20 changed modalities one or more times, each change of dialysis type (IHD or CAVHD) or anticoagulant protocol being considered as a new course of treatment. The study was non-randomized, with a demonstrable bias towards using Hep for patients at lower risk of bleeding, and Sal or Cit for higher risk patients. Despite this bias, new bleeding events occurred during 26% of 35 courses of HepIHD and HepCAVHD, and during 0% of 24 courses of CitIHD and CitCAVHD (P < 0.009). Troublesome dialyzer/filter clotting occurred during one course of HepCAVHD, and during 12% of 129 SalIHD procedures; 28% of 29 courses of SalIHD were terminated for this reason. CitCAVHD was well tolerated and proved superior to other modalities in freedom from bleeding events and clotting problems. Alternatives to heparin anticoagulation should be made available for high risk patients requiring acute extracorporeal therapy.

Acute Kidney Injury↗

Synthetic peptides of human CD4 enhance binding of Ig to monocyte/macrophage cells. I. Characterization and mapping studies.

Human T cell glycoprotein CD4 binds to class II MHC molecules and to HIV envelope protein gp120. We have shown that CD4 and synthetic peptides corresponding to amino acid residues 21-49 of the first extracellular domain of CD4, also bind Ig and, with greater avidity, antibody:Ag complex. We investigated the effect of CD4 synthetic peptides on the binding and uptake of human Ig by monocyte/macrophage U937 cells. We found that a synthetic peptide corresponding to amino acid residues 21-49 enhanced binding to U937 cells of both aggregated and nonaggregated Ig. The enhancement was concentration dependent, occurred both in normal and low ionic strength conditions, and varied with the time and the temperature of the preincubation step. The enhancement was maximal after preincubation for 3 h at 37 degrees C. A peptide concentration of 20 micrograms/ml was sufficient for optimal binding of both nonaggregated and aggregated Ig. CD4 peptide 21-49 also enhanced binding of Ig to Staphylococcus aureus protein A. These studies open a new perspective in the way monocyte/macrophage cells handle Ig, antibody:Ag or Id:anti-Id complex, in particular when present at threshold amounts in a nonprecipitating form.

Amino Acid Sequence↗

Interactions of the beta carboline abecarnil with the high pressure neurological syndrome in a primate model.

The neurophysiological interactions between the high pressure neurological syndrome (HPNS) and a new beta carboline, abecarnil, were studied in the non-human primate Papio anubis. Abecarnil is a partial agonist at the benzodiazepine site on the GABA/benzodiazepine receptor. Six animals were exposed on two occasions to pressures of 91 ATA in an environment of helium and oxygen. One exposure was pretreated with a total dose of abecarnil 1.0 mg/kg, the other with an equivalent volume of vehicle. Treatment with abecarnil prevented the severe signs of HPNS occurring between 51 and 91 ATA. Onset pressures of the various signs were unaffected. Some signs, e.g. myoclonus, became more frequent when abecarnil was used. A residual protective effect of abecarnil was present 4 weeks after the dose was given, active at pressures less than 71 ATA. Changes with pressure in the EEG were recorded primarily from the frontal cortex, but were also present in the parietal and occipital areas of the left cortex. Amplitude and frequency spectra were calculated and changes with pressure in the four conventional wavebands, plus two others, analysed. The most striking change was the prevention by abecarnil of the pressure-induced 100% increase in alpha wave amplitude in the frontal region. It is concluded that modulation of GABA transmission is important in controlling the expression of HPNS.

Animals↗

Acute renal failure associated with the use of intraperitoneal carboplatin: a report of two cases and review of the literature.

Carboplatin, a new analogue of cisplatin used in the treatment of ovarian carcinoma, has been demonstrated to be less nephrotoxic than its predecessor. To date, hundreds of cycles of therapy have been given without a significant incidence of renal failure. We report herein two cases of acute, nonoliguric renal failure in patients receiving intraperitoneal (IP) carboplatin as chemotherapy for advanced ovarian carcinoma. Each patient had received extensive previous treatment with cisplatin. The baseline serum creatinine levels in the patients were 0.9 and 1.1 mg/dL, respectively. After four cycles of IP carboplatin in Patient 1 and five cycles of IP carboplatin in Patient 2, the serum creatinine levels abruptly rose to 9.0 and 9.5 mg/dL, respectively, within a week after administration of therapy. No other primary etiologies for acute renal failure could be identified in either patient. One patient required hemodialysis briefly. Renal biopsy specimens were obtained from both patients. Patient 1 had focal and moderate interstitial nephritis with mild periglomerular fibrosis. Patient 2 had an edematous interstitium with a diffuse mononuclear cell infiltrate, focal interstitial hemorrhage, and toxic changes in proximal and distal tubules on electron microscopy. Treatment with oral prednisone at 1 mg/kg/day with a rapid taper over 4 weeks was done in both cases with the serum creatinine levels eventually dropping to 4.6 and 2.0 mg/dL, respectively. Acute interstitial nephritis and renal failure to this extent have not been previously reported with carboplatin therapy. The literature regarding carboplatin is reviewed with respect to the pathophysiology of its nephrotoxicity.

Acute Kidney Injury↗

Recent advances in continuous renal replacement therapy: citrate anticoagulated continuous arteriovenous hemodialysis.

Trisodium citrate was used as a regional anticoagulant on 24 patients on continuous arteriovenous hemodialysis (CAVHD), obviating the need for systemic heparinization. Principles of CAVHD, potential complications, and nursing responsibilities are addressed. Clearances, blood flow rate, ultrafiltration and filter patency compare favorably with heparin CAVHD. Citrate anticoagulated CAVHD avoids heparin-associated complications in the critically ill uremic patient.

Acute Kidney Injury↗

Skin necrosis associated with acquired protein C deficiency in patients with renal failure and calciphylaxis.

PURPOSE: To determine if the natural anticoagulant protein C plays a role in the pathogenesis of systemic calciphylaxis, a syndrome characterized by extensive vascular and soft tissue calcification and skin necrosis, which is similar to that seen in warfarin-induced skin necrosis. PATIENTS AND METHODS: The study population included five patients with end-stage renal disease and systemic calciphylaxis undergoing hemodialysis, 12 patients without evidence of calciphylaxis undergoing dialysis, eight patients with nephrotic syndrome, and eight normal healthy volunteers. Protein C antigen levels were measured by rocket immunoelectrophoresis, and functional activity was quantitated by a chromogenic assay and an anticoagulant assay utilizing the venom of Agkistrodon contortrix. RESULTS: Skin biopsy specimens of involved areas in three patients showed thrombotic occlusion of venules identical to that seen in warfarin-induced skin necrosis. Protein C antigen levels were normal in all groups. However, protein C activity was significantly reduced as measured by chromogenic (p less than 0.01) or anticoagulant assays (p less than 0.01) in patients with calciphylaxis compared with the other three groups. CONCLUSION: These findings suggest that hypercoagulability due to functional protein C deficiency may contribute to thrombosis, resulting in skin necrosis and digital gangrene in systemic calciphylaxis.

Adult↗

Effects of enflurane and isoflurane in air-oxygen on changes in thermal balance during and after surgery.

The temperatures in the aural canal (core), skeletal muscle and skin surface were measured during anaesthesia and surgery in 32 healthy females undergoing total abdominal hysterectomy and for 4 h after operation. The patients were allocated randomly to one of four groups according to the end-tidal concentration of volatile anaesthetic: 1 MAC isoflurane, 1 MAC enflurane, 1.8 MAC isoflurane and 1.8 MAC enflurane. The lungs were ventilated with an air-oxygen mixture. Neuromuscular block was produced with pancuronium. Room temperature and i.v. fluid administration were standardized. Aural canal, muscle and mean skin temperatures decreased significantly in all groups during surgery (P less than 0.001). The decrease in core and muscle temperatures, and mean body heat was significantly greater in the 1.8 MAC groups than in the 1 MAC groups for both volatile agents (P less than 0.001). However, there was a significantly greater decrease in core temperature and mean body heat in the isoflurane compared with the enflurane group (P less than 0.026). Body temperature returned to preoperative values during the recovery period. There was a significantly greater rate of rewarming during the first 1 h of recovery in the 1.8 MAC groups compared with the 1 MAC equivalent (P less than 0.001), and this was independent of the volatile agent used. The present results are compared with those reported previously in which nitrous oxide was added to the volatile agents. The decrease in body temperature depends upon the concentration of vapour used. However, it appears that isoflurane, without nitrous oxide, caused greater loss of body heat than enflurane.

Adult↗