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R Shrestha

Publications and source records attributed to R Shrestha.

32 records · Page 2Linked to original sources

Prednisone withdrawal 14 days after liver transplantation with mycophenolate: a prospective trial of cyclosporine and tacrolimus.

BACKGROUND: The long-term complications of immunosuppressive therapy such as diabetes, hypercholesterolemia, and hypertension are a major source of morbidity in liver transplant recipients. In this prospective, randomized, open-label study we completely withdrew prednisone (PRED) 14 days after liver transplantation in an effort to decrease these metabolic complications. Patients were maintained on mycophenolate mofetil (MMF) in combination with either cyclosporine (CsA; Neoral formulation) or tacrolimus (TAC). Thus, we also were able to compare CsA to TAC in patients not receiving PRED with respect to efficacy, toxicity, and effect on posttransplant metabolic complications. METHODS: A total of 71 patients were randomized to receive either TAC-MMF (n=35) or CsA-MMF (n=36) after liver transplantation and were analyzed for patient and graft survival. Fifty-eight patients continued the immunosuppressive protocol for at least 6 months after transplantation and were analyzed for the incidence of acute rejection and the prevalence of diabetes, hypertension, and hypercholesterolemia. RESULTS: The 6-month patient survival rates were 94.4% for CsA-MMF and 88.6% for TAC-MMF. Corresponding 6-month graft survival rates were 88.7% and 85.71% with no immunologic graft losses in either group. The incidence of biopsy-proven acute rejection was 46% for CsA-MMF and 42.3% for TAC-MMF. Six patients were converted from CsA to TAC (four for recurrent rejection) and seven patients were converted from TAC to CsA (four for neurotoxicity). Only one patient (in the TAC-MMF group) developed new-onset posttransplant diabetes. In contrast, four of eight patients in the CsA-MMF group who were diabetic before transplant became nondiabetic in the first 3 months after transplant. The mean serum cholesterol level was significantly lower in the TAC-MMF group than in the CsA-MMF group (145.2+/-41.8 mg/dl and 190.3+/-62.2, respectively; P<0.001) and the incidence of hypertension was lower in the TAC-MMF group (12% vs. 30.3% in the CsA-MMF group, P<0.01). Both groups had a lower incidence of metabolic complications compared with a historical group (n=100) maintained on CsA and PRED (10 mg/day at 6 months). CONCLUSIONS: MMF in combination with either TAC or CsA allows withdrawal of PRED 14 days after liver transplantation with a moderate rejection rate and no immunologic graft losses. Early PRED withdrawal decreases posttransplant diabetes, hypercholesterolemia, and hypertension, but patients maintained on TAC have lower serum cholesterol levels and a lower incidence of hypertension than CsA-treated patients.

Acute Disease↗

Prednisone withdrawal late after adult liver transplantation reduces diabetes, hypertension, and hypercholesterolemia without causing graft loss.

We prospectively withdrew prednisone in 28 adult patients who had stable graft function more than 2 years after orthotopic liver transplantation (OLTx) and had been on 5 mg/d prednisone for at least 6 months. Prednisone was decreased from 5 mg/d to 2.5 mg/d for 1 month then stopped completely. Cyclosporine monotherapy was maintained at a level of approximately 200 ng/mL (TDX). Nineteen patients had prednisone withdrawn without complications. Four (14.2%) had modest elevations in liver function tests (two biopsy proven mild rejections and two were not biopsied). These four were treated with methylprednisolone boluses and then withdrawal of steroids again. Prednisone was restarted in five patients because of generalized fatigue and body aches (n = 4) and colitis (n = 1). Steroids later were successfully withdrawn in two of these patients. After prednisone withdrawal, three of five insulin-dependent diabetic patients were able to discontinue insulin therapy and their glycosylated hemoglobin levels improved. Four of fourteen hypertensive patients were able to discontinue antihypertensive medicines. Mean serum cholesterol decreased from 222.6 +/- 43.3 to 188.3 +/- 33.3 mg/dL (P < .001). The number of patients with serum cholesterol levels > 220 mg/dL decreased from 13 to 4. A control group of 24 patients maintained on 5 mg/d prednisone at least 2 years after liver transplantation also was studied. In this group during the study period, no diabetic became normoglycemic, no patient decreased their antihypertensive medicine, and the mean serum cholesterol levels did not change significantly. We conclude that prednisone withdrawal using cyclosporine monotherapy late after liver transplantation does not lead to graft loss and decreases the prevalence of diabetes, hypertension, and hypercholesterolemia. Symptoms occurring during withdrawal may be minimized by earlier or slower tapering.

Adult↗

Quantitative liver function tests define the functional severity of liver disease in early-stage cirrhosis.

Some patients with early-stage cirrhosis preserve hepatic function, whereas others have little hepatic reserve and rapidly deteriorate. The aim of this study was to use quantitative tests of liver function (QLFTs) to define the degree of functional hepatic impairment in patients with early-stage cirrhosis (Child-Pugh score 5-7) and to determine whether the tests predicted subsequent hepatic decompensation. We recruited 10 cirrhotic (Cr) patients and 10 healthy controls (NI), who were well matched for race, age, weight, and gender. Clearances of caffeine (CF) and antipyrine (AP) after oral administration were measured from timed samples of saliva. The clearance of cholate (CA) was measured from serum samples obtained after simultaneous oral ([2,2,4,4-2H]CA) and intravenous ([24-13C]CA) administration. CA shunt was calculated as (Cl i.v./Clo x 100%). CF elimination rate (Cr v NI, mean +/- SD: 0.03 +/- 0.02 v 0.075 +/- 0.018 h-1, P < .0005) and AP clearance (24 +/- 16 v 40 +/- 7 mL/minute, P < .02) were reduced in Cr patients. CA shunt was increased in Cr patients (43 +/- 18 v 18 +/- 7%, P < .002). Five Cr patients decompensated during follow-up and had the worst CA shunts (76%, 66%, 51%, 48%, and 45%). Three subsequently received successful orthotopic liver transplantation, 1 died of hepatoma, and 1 is on the waiting list for transplantation. In conclusion, QLFTs define the degree of functional impairment in early cirrhosis and may identify Cr patients at greatest risk of decompensation who may require transplantation for survival.

Administration, Oral↗

Use of transjugular intrahepatic portosystemic shunt as a bridge to transplantation in fulminant hepatic failure due to Budd-Chiari syndrome.

We report a case of fulminant hepatic failure in a 55-yr-old man due to Budd-Chiari syndrome in the setting of polycythemia rubra vera. The patient presented with acute hepatic failure, which rapidly progressed to grade IV hepatic encephalopathy. Placement of a transjugular intrahepatic portosystemic shunt resulted in marked improvement of the encephalopathy and stabilized the liver failure. Subsequently, he underwent successful nonemergent orthotopic liver transplantation. Transjugular intrahepatic portosystemic shunt placement is a safe, effective, therapeutic option to bridge patients with fulminant Budd-Chiari to liver transplantation.

Brain Edema↗

Endoscopic stenting of gallbladder for symptomatic cholelithiasis in patients with end-stage liver disease awaiting orthotopic liver transplantation.

Cholecystectomy in patients with advanced cirrhosis is associated with excessive morbidity and mortality. Symptomatic cholelithiasis in patients awaiting orthotopic liver transplantation poses unique management issues. Three patients with end-stage liver disease, severe enough to warrant hepatic transplantation, developed symptoms and complications of cholelithiasis requiring intervention. Each underwent placement of a biliary stent from gallbladder to duodenum at endoscopic retrograde cholangiopancreatogram. In each case, biliary symptoms and complications ceased after stent placement. Two patients remained symptom-free until they underwent successful liver transplantation, and the third awaits transplant and is currently free of symptoms of cholelithiasis. Endoscopic placement of gallbladder stents represents a temporizing alternative for the management of patients with symptomatic cholelithiasis awaiting hepatic transplantation.

Adult↗

Distribution of taste buds on the epiglottis of the rat and house shrew, with special reference to air and food pathways.

We investigated the positioning of the epiglottis in the pharyngo-laryngeal region and the distribution of taste buds on the epiglottis in the rat and house shrew, animals which have different feeding habits. In the fixed samples of both species, when the mouth was closed or slightly opened, the epiglottis was found to protrude into the nasopharyngeal hiatus above the soft palate. But it retracted from its position when the mouth was widely opened. In omnivorous rats (n = 6), the mean number (mean density +/- s.d.) of taste buds was 52 (12.6 +/- 2.2/mm2) on the laryngeal surface but only 4 (1.3 +/- 1.0/mm2) on the oral surface. The three-dimensional view was reconstructed from serial sections. The taste buds were distributed most densely close to the caudal base and became fewer toward the more rostral tip. In insectivorous house shrews (n = 2), 4 taste buds on average were found only on the laryngeal surface of the epiglottis. Epiglottal taste buds may work as chemosensory detectors to initiate the reflex reaction to protect the airway from oral substances during swallowing and drinking.

Animals↗

Possible idiopathic thrombocytopenic purpura associated with natural alpha interferon therapy for chronic hepatitis C infection.

We report the case of a 41-yr-old male with chronic hepatitis C who developed severe thrombocytopenia on interferon alfa-n3 therapy. The patient was enrolled in a multi-center trial of interferon alfa-n3 in the treatment of chronic hepatitis C. In the 10th wk of therapy, he presented with gingival bleeding and a petechial rash. Complete blood count demonstrated WBC 5,800/mm3. Hgb 16.3 g/dl, Hct 45.5%, and platelet count 6,000/mm3. Interferon was withdrawn, and he was admitted to intensive care and was treated with platelet transfusion, intravenous steroids, and intravenous immunoglobulin. His platelet counts returned to 157,000/mm3 in 7 days and remained normal on a tapering dose of prednisone. Bone marrow biopsy/aspirate demonstrated numerous megakaryocytes. Stored plasma was negative for development of specific high-titer anti-platelet antibody. We suggest that the clinical findings and response to therapy are consistent with interferon-induced idiopathic thrombocytopenic purpura.

Adult↗

Idiopathic colonic varices: an unusual cause of massive lower gastrointestinal hemorrhage.

We report a patient with massive lower gastrointestinal bleeding, probably from extensive colonic varices. Despite lengthy investigation, the etiology of the colonic varices was not determined. There are numerous reports in the literature of bleeding from colonic varices attributed to portal hypertension from cirrhosis or venous obstruction. However, bleeding from colonic varices located in the entire colon without demonstrable cause have only rarely been reported.

Adult↗

Epilepsy in children: an epidemiological study at Kathmandu Medical College Teaching Hospital Kathmandu.

OBJECTIVES: To analyze the relative frequencies of various epileptic seizures and to study the age at onset of different seizure types in Nepalese children. DESIGN: Prospective study. SETTING: Hospital outpatient based in Kathmandu, Nepal, between November 2001 to October 2002. PARTICIPANTS: 50 children diagnosed as epilepsy excluding neonatal and febrile seizures. MAIN OUTCOME MEASURE: Diagnosis and classification of cases according to the International Classification of Epilepsy of the International League Against Epilepsy [ILAE] and number of patients in each category with various ages at first seizure. RESULT: Generalized seizures (78%) were 3.54 times commoner than partial seizures (22%). Most frequent seizure types were generalized tonic clonic (36%), tonic (16%), complex partial (14%), atonic (12%) and absence (10%). Generalized clonic, simple partial and partial with secondary generalization, each had less than 5% frequencies. In 40% cases the first seizure occurred when aged between 2-5 years. In partial seizures the peak age at onset was observed below 6 years while primary generalized seizure was more frequently seen in age group 2-10 years. CONCLUSION: More paediatric patients with primary generalized seizures (78%) were observed than with partial seizures (22%). In this age group, the most frequent seizure type was generalized tonic clonic (36%) with the peak frequency of age at onset of seizures in 2-5 years.

Adolescent↗

Hepatitis E virus infection in chronic liver disease causes rapid decompensation.

Hepatitis E previously known as enterically transmitted non-A, non-B hepatitis, is a self limiting infectious viral disease of developing countries. Various issues regarding the pathogenesis of liver injury and its natural history remain unanswered after two decades of its discovery. A small proportion of patients develop fulminant hepatic failure. Mortality is very high if it is associated with pregnancy, especially during third trimester. After establishment of hepatitis A virus as a cause of decompensation of chronic liver disease, now there are reports that hepatitis E viruses also does the same. Acute hepatitis E in these patients has a protracted course with high morbidity and mortality. Many patients develop hepatorenal syndrome, hepatic encephalopathy and even liver failure after co-infection with hepatitis E virus. Now time has come to institute hepatitis E virus superinfection as one of the cause of acute on chronic liver failure. Hepatitis E is a problem of developing countries and Nepal is in the endemic zone. Sudden decompensation in chronic liver disease patient, who were otherwise stable and under regular follow up, should be carefully dealt with. Patient statistics at our unit shows that 7 cases of chronic liver diseases with superinfection with hepatitis E virus were dealt from April 2004 to August 2005. Two patients (29%) died and 5 recovered. In patients with recovery, there was deterioration of Child-Pugh grading and the duration of hospital stay was longer. Thus, hepatitis E in diagnosed chronic liver disease case should be taken apprehensively. Similarly patients of chronic liver disease traveling to endemic zone should take precaution. If vaccine against hepatitis E virus is developed, chronic liver disease patient would be the eligible candidate for vaccination beside pregnant ladies.

Adult↗