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Biomedical subjects

B V Murthy

Publications and source records attributed to B V Murthy.

At least 19 recordsLinked to original sources

Pharmacokinetics of tramadol in children after i.v. or caudal epidural administration.

We have studied the pharmacokinetics of a single bolus dose of tramadol 2 mg kg-1 injected either i.v. or into the caudal epidural space in 14 healthy children, aged 1-12 yr, undergoing elective limb, urogenital or thoracic surgery. Serum concentrations of tramadol and its metabolite O-demethyl tramadol (MI) were measured in venous blood samples at various intervals up to 20 h by non-stereoselective gas chromatography with nitrogen-selective detection. All pharmacokinetic variables were evaluated using a non-compartmental model. After a single i.v. injection (n = 9), the mean elimination half-life of tramadol was 6.4 (SD 2.7) h, with a volume of distribution of 3.1 (1.1) litre kg-1 and total plasma clearance of 6.1 (2.5) ml kg-1 min-1. All of these pharmacokinetic variables were similar to those reported previously in adults. After caudal epidural administration (n = 5), mean elimination half-life was 3.7 (0.9) h, volume of distribution was 2.0 (0.4) litre kg-1 and total clearance was 6.6 (1.9) ml kg-1 min-1. The caudal/i.v. quotient of the AUC was 0.83, which confirms that there is extensive systemic absorption of tramadol after caudal administration. Serum concentrations of MI showed a time course typical of a metabolite after both modes of administration. Serum concentrations of MI after caudal administration were lower than those after i.v. injection.

Analgesia↗

Comparison of the effects of topical lignocaine spray applied before or after induction of anaesthesia on the pressor response to direct laryngoscopy and intubation.

In an attempt to attenuate the cardiovascular pressor response to laryngoscopy and intubation, 30 patients presenting for routine ophthalmic surgery were studied and were randomly allocated into two groups: group A (n = 15) received direct laryngeal/tracheal lignocaine spray immediately before intubation; and group B (n = 15) received orolaryngeal lignocaine spray before the induction of anaesthesia. In both groups, general anaesthesia was induced with thiopentone 3-5 mg kg-1, followed by atracurium 0.6 mg kg-1 to facilitate tracheal intubation. Laryngoscopy and endotracheal intubation caused a significant increase in heart rate, by 28% in group A and 23% in group B (P < 0.05 in both), and in diastolic blood pressure, by 28% in group A and 24% in group B (P < 0.05 in both). In group A, the systolic blood pressure also increased significantly (by 18%) after intubation, but there was no significant change in group B. In addition, the plasma lignocaine concentrations remained well below the toxic range in both groups. It was concluded that topical lignocaine administration as an orolaryngeal spray before the induction of anaesthesia is effective in reducing but not abolishing the pressor response to laryngoscopy and endotracheal intubation.

Administration, Topical↗

Intestinal pseudo-obstruction associated with oral morphine.

Morphine is recommended as the strong opioid of choice by the World Health Organization (WHO) for cancer pain management. It is associated with delay in gastro-intestinal transit; as a result, patients may experience marked constipation. We describe a case of intestinal pseudo-obstruction associated with the use of oral morphine in a terminally ill cancer patient.

Administration, Oral↗

Effects of hepatitis C infection and renal transplantation on survival in end-stage renal disease. The New England Organ Bank Hepatitis C Study Group.

Hepatitis C virus (HCV) infection is common among patients with end-stage renal disease (ESRD). However, the effect of HCV infection on survival among ESRD patients, and the impact of renal transplantation on the course of HCV infection has not been adequately defined. Sera from patients on the renal transplant waiting list at the New England Organ Bank between November 1986 and June 1990 were tested for anti-HCV using a third generation ELISA. All anti-HCV positive patients and a 1:1 ratio of randomly selected anti-HCV negative patients comprised the study sample. Duration of follow-up was calculated from the date of the first available serum specimen until death, loss to follow-up or December 31, 1995, whichever occurred earlier. Multivariate analysis of risk factors for mortality was performed using a Cox proportional hazards model which included anti-HCV as a time-independent (baseline) variable, transplantation as a time-dependent (follow-up) variable, and independently significant baseline covariates. Anti-HCV was detected in 287 (19%) of 1544 patients in whom sera were available, and 286 anti-HCV negative patients served as controls. Complete information was available in 496 (87%) of these 573 patients. Median follow-up was 73 months (range 1 to 110 months), during which time 302 (61%) patients underwent renal transplantation and 154 (31%) patients died. For anti-HCV positive patients compared to anti-HCV negative patients, the relative risk of death (and 95% confidence intervals) from all causes was 1.41 (1.01 to 1.97) and due to liver disease or infection was 2.39 (1.28 to 4.48). For patients who underwent transplantation compared to those who remained on dialysis, the relative risk of death from all causes between 0 to 3 months, 3 to 6 months, seven months to four years, and after four years was 4.75 (2.76 to 8.17), 1.76 (0.75 to 4.13), 0.31 (0.18 to 0.54) and 0.84 (0.51 to 1.37), respectively. There was no interaction between the effect of anti-HCV status as baseline and subsequent transplantation (P = 0.93), meaning that the association between treatment modality and survival was similar among anti-HCV positive and negative patients, at all intervals after transplantation. We conclude that HCV infection at the time of referral for transplantation is associated with an increased risk of death, irrespective of whether patients remain on dialysis or undergo transplantation. Transplantation has a beneficial rather than adverse effect on long-term survival in anti-HCV positive patients. Hence, anti-HCV positive status alone is not a contraindication for renal transplantation.

Adolescent↗

Predictors of GBV-C infection among patients referred for renal transplantation.

The etiology of liver disease remains unknown in about 4 to 23% of dialysis patients and 10 to 16% of renal transplant recipients. A search for other causative agents of liver disease led to the discovery of the GB group of viruses. We studied the association between the presence of GB virus C (GBV-C) infection, known risk factors for parenterally-transmitted infections and history or laboratory evidence of liver disease among end-stage renal disease (ESRD) patients referred for renal transplantation to the New England Organ Bank, MA. Stored sera from patients on the renal transplantation waiting list between November 1986 and June 1990 were tested for antibody to hepatitis C virus (HCV). Sera were available in 1544 of 3243 (48%) patients, and anti-HCV was detected by ELISA3 in 287 (19%). All 287 anti-HCV positive patients formed the anti-HCV positive cohort and 286 randomly selected anti-HCV negative patients formed the anti-HCV negative cohort (573 patients overall). Additional sera were available for GBV-C RNA testing in 465 of 573 (81%) patients, and GBV-C RNA was detected by RT-PCR in 146. The overall extrapolated prevalence of serum GBV-C RNA was 29%. The prevalence of serum GBV-C RNa among anti-HCV positive patients (35%) was not significantly different from that among anti-HCV negative patients (29%; P = 0.22). In a univariate analysis, compared to patients without GBV-C RNA, patients with serum GBV-C RNA were younger [odds ratio (OR) 0.98 per year of age, P = 0.01], had a lower proportion of males (OR 0.64, P = 0.03), lower proportion of patients with diabetes mellitus (OR 0.44, P = 0.01), higher proportion of patients with a previous transplantation (OR 1.53, P = 0.04), longer duration of dialysis at the time of enrollment (OR 1.004 per month on dialysis, P = 0.03), and a higher proportion of patients with history of transfusions (OR 4.58, P = 0.01). Serum GBV-C RNA was not associated with a significantly increased OR for history of liver disease or non-A, non-B hepatitis, or elevated serum alanine aminotransferase levels. In a step-wise multivariate regression analysis, a younger age (OR 0.98 per year of age, P = 0.03), and history of blood transfusions (OR 3.89, P = 0.03) were associated with an increased OR for serum GBV-C RNA, while diabetes mellitus was associated with a decreased OR for GBV-C RNA (OR 0.47, P = 0.01). Anti-HCV was not a predictor of serum GBV-C RNA (OR 1.07, P = 0.77). The results of this study support the fact that GBV-C is a parenterally transmitted virus and shed light on the modes of transmission of GBV-C among ESRD patients. However, the association with liver disease remains to be established.

Adolescent↗

Serologic and virologic profiles of hepatitis C infection in renal transplant candidates. New England Organ Bank Hepatitis C Study Group.

The development of policies to prevent nosocomial transmission of hepatitis C virus (HCV) infection in hemodialysis units is critically dependent on the understanding of the relationship between tests for anti-HCV, HCV RNA, and HCV genotype and the patients' clinical characteristics. We tested sera from all patients on the renal transplant waiting list at the New England Organ Bank between November 1986 and June 1990 for anti-HCV by a third-generation enzyme-linked immunosorbent assay (ELISA3) and a third-generation recombinant immunoblot assay (RIBA3). All ELISA3-positive sera were tested for HCV RNA by reverse transcriptase "nested" polymerase chain reaction, and the genotype was characterized by restriction fragment length polymorphism. Sera were available in 1,544 of 3,243 (48%) patients on the waiting list, of whom 287 (19%) tested positive for anti-HCV by ELISA3. Two hundred eighty-six randomly selected, anti-HCV-negative patients served as controls. Compared with anti-HCV-negative controls, anti-HCV-positive patients had a longer duration since initiation of renal replacement therapy, higher number of previous kidney transplants and blood transfusions, higher proportion of patients with anti-HBc, history of liver disease, history of non-A, non-B hepatitis, and elevated serum alanine aminotransferase, and lower serum albumin concentrations. Of the 287 anti-HCV-positive sera, 261 (91%) were reactive by RIBA3, 21 (7%) were indeterminate, and five (2%) were nonreactive. HCV RNA was detected in 224 of 275 (81%) ELISA3-positive patients, in whom additional sera were available. There were no significant differences in clinical or laboratory characteristics between ELISA3-positive patients with and without HCV RNA. Genotypes 1a, 1b, 2a, 2b, 3a, and 4 were present in 53%, 23%, 8%, 10%, 4%, and 2% of patients, respectively. Infection with one, two, or three different HCV genotypes was present in 92%, 7%, and 1%, respectively. There was no significant association between the type or number of HCV genotypes and RIBA3 reactivity. There were no major differences in clinical or laboratory characteristics between genotypes or between single and mixed infection. In summary, this study provides detailed information regarding the relationship between tests for anti-HCV, HCV RNA, and HCV genotypes and the clinical and laboratory characteristics of a large, well-characterized cohort of patients referred for renal transplant.

Enzyme-Linked Immunosorbent Assay↗

Effect of formaldehyde/bleach reprocessing on in vivo performances of high-efficiency cellulose and high-flux polysulfone dialyzers.

Among the several disadvantages of reprocessed dialyzers is the concern that reuse could decrease the clearance of uremic toxins, leading to a decrease in the delivered dose of dialysis. To examine this possibility in the clinical setting, the clearances of small molecular weight solutes (urea and creatinine) and middle molecular weight substances (beta 2 microglobulin) were compared during dialysis with "high-efficiency" cellulose (T220L) and "high-flux" polysulfone (F80B) dialyzers reprocessed with formaldehyde and bleach. In a crossover study, six chronic hemodialysis patients were alternately assigned to undergo 21 dialysis treatments with a single T220L dialyzer or F80B dialyzer. Each patient was studied during first use (0 reuse), 2nd reuse (3rd use), and 5th, 10th, 15th, and 20th reuse of each dialyzer. Urea, creatinine, and beta 2 microglobulin clearances were measured at blood flow rates of 300 ml/min (Qb 300) and 400 ml/min (Qb 400). Total albumin loss into the dialysate was measured during each treatment. Urea or creatinine clearance of new T220L dialyzers was not significantly different from that of new F80B dialyzers at either Qb. Urea clearance of F80B dialyzers at Qb 300 decreased from 241 +/- 2 ml/min for new dialyzers to 221 +/- 5 ml/min after 20 reuses (P < 0.001), and Qb 400 from 280 +/- 4 ml/min for new dialyzers to 253 +/- 7 ml/min after 20 reuses (P = 0.001). Similarly, with reuse, creatinine clearance of F80B dialyzers also decreased at Qb 300 (P = 0.07) and Qb 400 (P = 0.03). In contrast, urea or creatinine clearance of T220L dialyzers did not decrease with reuse at either Qb. Urea clearance of T220L dialyzers was significantly higher than that of F80B at Qb 300 at the 5th, 10th, 15th, and 20th reuse (P < 0.001, = 0.005, = 0.004, and = 0.006, respectively), and Qb 400 at the 2nd, 5th, 10th, 15th, and 20th reuse (P = 0.04, 0.008, 0.03, 0.02, and 0.008, respectively). Beta 2 microglobulin clearance of T220L dialyzers was < 5.0 ml/min across the reuses studied. Beta 2 microglobulin clearance of F80B was < 5.0 ml/min for new dialyzers, but increased to 21.2 +/- 5.3 ml/min (Qb 300) and 23.6 +/- 3.3 ml/min (Qb 400) after 20 reuses (P < 0.001). Throughout the study, albumin was undetectable in the dialysate with T220L dialyzers. With F80B dialyzers, albumin was detected in the dialysate in four instances (total loss during dialysis, 483 mg to 1.467 g). In summary, the results of this study emphasize the greater need for information on dialyzer clearances during clinical dialysis, especially with reprocessed dialyzers. A more accurate knowledge of dialyzer performance in vivo would help to ensure that the dose of dialysis prescribed is indeed delivered to the patients.

Albumins↗

Long-term follow-up of hepatitis C virus infection among organ transplant recipients: implications for policies on organ procurement.

BACKGROUND: Hepatitis C virus (HCV) infection causes slowly progressive liver disease. Therefore, the full impact of HCV infection after transplantation may require 5-10 years of follow-up. METHODS: We have previously reported the effect of HCV infection, acquired from the donor (study 1) or acquired before transplantation (study 2), on the incidence of liver disease, and on patient and graft survival with a median follow-up of 3-5 years. In study 1, we compared 24 recipients of organs from donors who were positive to antibody to HCV (anti-HCV) to 74 recipients of organs from anti-HCV-negative donors. In study 2, we compared 23 anti-HCV-positive recipients to 80 anti-HCV-negative recipients of kidneys from anti-HCV-negative donors. In this report, we extend the median follow-up period for patient and graft survival to 6-7 years, and discuss the implications of our finding on policies for organ procurement. RESULTS: In study 2, after extended follow-up, there continued to be no significant difference between groups with respect to graft loss, but mortality remained significantly higher among recipients with anti-HCV before transplantation. Compared with recipients without anti-HCV before transplantation, the relative risk of graft loss among recipients with anti-HCV before transplantation was 1.30 (0.66-2.58), the relative risk of death was 2.60 (1.15-5.90), and the relative risk of death due to sepsis was 6.30 (1.99-20). In study 1, after extended follow-up, there continued to be no significant differences between groups, with respect to graft loss or death. Compared with recipients of organs from anti-HCV-negative donors, the relative risk of graft loss among recipients of organs from anti-HCV-positive donors was 0.95 (0.54-1.67), and the relative risk of death was 1.00 (0.49-2.02). CONCLUSIONS: The two studies presented in this report provide an apparent paradox, with respect to the impact of HCV infection acquired at the time of transplantation versus before transplantation on posttransplantation clinical outcomes. However, the increased mortality among recipients who acquired HCV infection before transplantation, but not among recipients who acquired HCV at the time of transplantation, could be explained by the longer duration of HCV infection in the former group. These findings are consistent with the known slowly progressive nature of HCV infection. However, in the absence of definitive evidence for an adverse effect on patient or graft survival, we believe that the decision to accept a kidney from an anti-HCV-positive donor should be made by the patient, after discussion with the treating physician.

Follow-Up Studies↗

GB hepatitis agent in cadaver organ donors and their recipients.

BACKGROUND: The cloning of yet another hepatitis virus, GB virus-C (GBV-C), has provided the opportunity to study the prevalence, and clinical and laboratory characteristics, associated with GBV-C infection among cadaver organ donors and recipients of organs from infected donors. METHODS: Stored sera from a cohort of cadaver organ donors from eight organ procurement organizations, representing different geographic regions of the United States previously screened for hepatitis C virus (HCV) infection, were tested for GBV-C RNA by polymerase chain reaction using degenerate primers derived from the NS3 helicase and 5'-untranslated regions of the GBV-C genome. Pre- and posttransplantation clinical data, and prevalence of GBV-C RNA among recipients of organs from GBV-C RNA-positive and -negative donors, were studied at one of the organ procurement organizations. RESULTS: Twenty-one of 76 (27.6%) anti-HCV ELISA1-positive donors tested positive for GBV-C RNA compared with 6 of 82 (7.3%) ELISA1-negative donors (P=0.001). The prevalence of GBV-C RNA, extrapolated to all cadaver organ donors, was 8.3% (95% confidence interval [CI]: 5.6-11.1%) and was higher than the prevalence of HCV RNA (2.4%). Among ELISA1-positive donors, GBV-C RNA was present in 13 of 35 (37%) donors with HCV RNA, compared with 8 of 41 (20%) donors without HCV RNA (odds ratio [OR]=2.44, P=0.09). Blood alcohol level of more than 100 mg/dl (OR=9.43, P=0.05) and a positive anti-HCV ELISA2 (OR=4.58, P=0.001) were significantly associated with GBV-C infection. In addition, there was a trend toward an association between history of drug abuse (OR=5.23, P=0.06) and younger age (OR=0.97/year, P=0.06) with GBV-C infection. Organs from four GBVC-positive donors and 47 GBV-C-negative donors procured by the New England Organ Bank (Newton, MA) were transplanted into 6 and 79 recipients, respectively. Among recipients of organs from GBV-C RNA. positive donors, the posttransplantation prevalence of GBV-C RNA (25%) was not significantly higher than among recipients of organs from GBV-C RNA-negative donors (23%). Among recipients in whom both pre- and posttransplantation sera were available, one of three (33%) recipients of kidneys from GBV-C RNA-positive donors acquired GBV-C RNA after transplantation, compared with 4 of 40 (10%) recipients of kidneys from GBV-C RNA-negative donors. After a median follow up of 6 years, the posttransplantation prevalence of liver disease, and graft and patient survival, were not significantly different between recipients of organs from GBV-C RNA-positive and -negative donors. CONCLUSIONS: Although GBV-C could be transmitted by organ transplantation, the results of this study preclude definitive conclusions. Further studies are required to determine the risk of transmission of GBV-C by organ transplantation and its role in posttransplantation liver disease.

Adolescent↗

Metabolic, biochemical and haemodynamic effects of infusion of propofol for long-term sedation of children undergoing intensive care.

We have studied prospectively, in nine children requiring sedation to facilitate mechanical ventilation, the metabolic, biochemical and haemodynamic effects of infusion of propofol. Children were given infusions of propofol 1-4mg kg-1 h-1 and fentanyl 1-5 micrograms kg-1 h-1 for 48 h. Heart rate, arterial pressure, central venous pressure, fluid balance and urine output were recorded hourly and sedation scores every 4 h. In addition to routine haemodynamic and biochemical measurements in the intensive care, 6-hourly arterial blood-gas analysis and 12-hourly measurements of serum concentrations of glucose, lactate and electrolytes, renal function, triglycerides and liver function tests were performed. Urine was analysed for ketones. There were no significant differences in haemodynamic or biochemical variables during the 48-h period. In this small sample of children, propofol combined with fentanyl provided excellent sedation with no evidence of cardiac, renal or hepatic impairment. Under these very proscriptive conditions we did not encounter lipaemia or acidosis with infusion of propofol. Thus propofol may be a safe sedative agent for use in paediatric intensive care if used appropriately. Further large scale studies are needed to determine if warnings against the use of this agent in paediatric intensive care units are justified.

Acid-Base Equilibrium↗

Impact of pretransplantation GB virus C infection on the outcome of renal transplantation.

Among renal transplant recipients with posttransplantation liver disease, the etiology remains unknown in 10 to 16% of patients. The discovery of yet another parenterally transmitted hepatitis virus, GB virus C (GBV-C), has opened avenues to study the prevalence and risk factors for GBV-C infection among patients undergoing renal transplantation and its impact on posttransplantation clinical outcomes. A cohort of 103 randomly selected recipients of kidneys were examined from anti-hepatitis C virus (HCV)-negative donors between 1986 and 1990. Pretransplantation sera were available in 99 of 103 (96%) recipients and were tested for anti-HCV, using a second-generation ELISA, and for GBV-C RNA by reverse transcription PCR. Pretransplantation GBV-C RNA was present in 18 of 99 (18%, 95% confidence interval [CI], 17.2 to 18.8%) recipients. GBV-C RNA was present in 5 of 22 (23%) anti-HCV-positive recipients compared with 13 of 77 (17%) anti-HCV-negative recipients (P = 0.53). The median number of pretransplantation blood transfusion among recipients with GBV-C RNA before transplantation was significantly higher than among recipients without GBV-C RNA (10 versus 7, P = 0.05). Posttransplantation liver disease and non-A, non-B hepatitis (NANBH) was observed in 35 and 18%, respectively, of GBV-C RNA-positive recipients compared with 28 and 10%, respectively, of GBV-C RNA-negative recipients. Using Cox regression analysis, the relative risk (RR) of posttransplantation liver disease among recipients with GBV-C RNA before transplantation was 1.37 (95% CI, 0.55 to 3.41), and posttransplantation NANBH was 2.09 (95% CI, 0.64 to 6.79). The RR of graft loss and death were not increased (0.88 and 0.92, respectively). When adjusted for pretransplantation anti-HCV, the RR of posttransplantation liver disease, NANBH, graft loss, and death did not change appreciably. In summary, although a higher risk of posttransplantation liver disease was observed among recipients with pretransplantation GBV-C infection, the analyses presented here do not allow for a precise estimate of this risk.

Adult↗