Comparison of renal safety and efficacy of telbivudine, entecavir and tenofovir treatment in chronic hepatitis B patients: real world experience.

This study aims to assess the nephrotoxicity and efficacy of tenofovir disoproxil fumarate (tenofovir), telbivudine and entecavir. A retrospective study of 587 patients with chronic hepatitis B treated with tenofovir (n = 170), telbivudine (n = 184) and entecavir (n = 233) for at least 1 year. Renal function and efficacy were assessed. The estimated glomerular filtration rate (eGFR) decreased significantly in the tenofovir group after a mean of 17 months treatment (from 92.2 to 85.6 mL/min/1.73 m(2), p < 0.001), but increased in the telbivudine group after a mean of 32 months of treatment (from 86.1 to 95 mL/min/1.73 m(2), p < 0.001). There was no significant change in eGFR in the entecavir group after a mean of 44 months. By multivariate analysis, pre-existing renal insufficiency (p = 0.003), tenofovir (p = 0.007) and diuretic treatment (p = 0.001) were independent predictors for renal function deterioration. Cumulative virological breakthrough was 0% in tenofovir after 2 years, 3.4% in entecavir after 7 years and 22.9% in telbivudine after 5 years. Liver cirrhosis (p = 0.008) and virological breakthrough (p = 0.040) were independently associated with increased risk of hepatocellular carcinoma development. Tenofovir may lead to deterioration in renal function as assessed by serial eGFR measurements. Although telbivudine appeared to be associated with an improvement in eGFR, it was associated with high rates of virological breakthrough, which was an independent risk factor for HCC development. With low rates of virological breakthrough and preservation of renal function, entecavir could be the best choice among these three agents.

Predictive factors for inadequate colon preparation before colonoscopy.

BACKGROUND: It could be helpful to ascertain which patients are at risk of poor bowel preparation prior to performing sedated colonoscopy. The aim of the present study was to identify the predictive factors for poor colon preparation prior to colonoscopy. METHODS: A prospective study was performed at Kaohsiung Chang Gung Memorial Hospital, Taiwan, from September 2011 to May 2013. Patient characteristics, food consumed within 2 days of colonoscopy, volume of polyethylene glycol (PEG) solution, interval between completing PEG and examination, number of bowel movements, and character of the last stool were evaluated. RESULTS: Seven hundred and three patients were enrolled (mean age 50.3 ± 11.6 years, 43 % female). In univariate analysis, character of the last stool (<0.001), body weight (p = 0.007), body mass index (p = 0.047), waist circumference (p = 0.008), buttock girth (p = 0.016), meal residue score (<0.001), and interval between end of PEG and colonoscopy (p = 0.01) were related to inadequate colon preparation. In multivariate analysis, waist circumference (p < 0.001), meal residue score (p < 0.001), and characteristics of last stool (p < 0.001) were variables that predicted poor colon preparation. CONCLUSIONS: Patients who have consumed a high residue diet and/or who report that their last stool is semisolid are likely to have poor bowel preparation, and consideration could be given to rescheduling the examination.

Risk factors influencing the outcome of peptic ulcer bleeding in end stage renal diseases after initial endoscopic haemostasis.

Background and Aims: Patients suffering from peptic ulcer (PU) bleeding who have end-stage renal disease (ESRD) may encounter more adverse outcomes. The primary objective is to investigate the risk factors that influence the outcomes of ESRD and chronic kidney disease (CKD) patients with PU bleeding after successful initial endoscopic haemostasis. Methods: A total of 540 patients with PU bleeding after initial endoscopic haemostasis in a tertiary hospital were investigated retrospectively. They were sorted into three groups after randomised age-matched adjustment: ESRD group (n = 90), CKD group (n = 90) and control group (n = 360). Main outcome measurements were rebleeding, requirement for blood transfusion and surgery, length of hospital stay and mortality. Results: The rebleeding rates were 43% for the ESRD group vs. 21% for the CKD group vs. 12% for the control group (overall p = < 0.001). Multivariate analysis showed the predictors of rebleeding were ESRD, time to endoscope, and non-high-dose proton-pump inhibitors (PPI) users. The risk factors for bleeding-related mortality were presence of moderate degree of CKD and ESRD group, time to endoscope, and Rockall score. All-cause mortality was related to presence of moderate degree of CKD and ESRD group, platelet count, time to endoscope, Rockall score and length of hospital stay. Conclusions: ESRD patients who suffered from PU bleeding were at risk of excessive rebleeding and mortality with frequent occurrence of delayed rebleeding. This study suggests that early endoscopy for initial haemostasis and high-dose intravenous PPI are associated with the reduction of rebleeding risk especially in patients with high Rockall scores.

Factors influencing clinical applications of endoscopic balloon dilation for benign esophageal strictures.

BACKGROUND AND STUDY AIMS: The purpose of this study was to investigate the safety and clinical effectiveness of a controlled radial expansion (CRE) balloon catheter in dilating benign esophageal strictures, and to assess factors influencing the effectiveness of this procedure. PATIENTS AND METHODS: From February 2000 to June 2002, 25 patients with documented benign esophageal strictures at our hospital were enrolled and treated with CRE balloon dilation. There were 17 men and eight women, with ages ranging from 30 to 82 years. The average age of the enrolled patients was 56.1 years. All of the strictures were dilated using CRE dilators under direct visualization, without fluoroscopic monitoring. The dilation diameters were planned in series up to 15 mm using a "rule of three". If dysphagia and esophageal strictures recurred during the clinical follow-up after completion of a series of dilations, additional dilation was carried out until symptomatic relief was achieved. Effective treatment was defined as the ability of patients with or without repeated dilations to maintain a solid or semisolid diet for more than 12 months. Depending on the effectiveness and duration of treatment, the patients were divided into three groups: group A, the successful group in which the initial series of dilations was effective without the need for any additional dilation for recurrent strictures or dysphagia; group B, the relapse group, in which the initial series of dilations was effective, but additional dilations were needed due to recurrent strictures or dysphagia; and group C, the group in which the initial series of dilations failed or consecutive dilations could not be carried out due to intolerance. RESULTS: The 25 patients received a total of 95 sessions of dilation (3.8 +/- 1.2 sessions per patient). There were 11 patients in group A, 11 patients in group B, and three patients in group C. The median follow-up period was 16.5 months (range 12 - 32 months). The number of initial dilations required to achieve symptomatic relief showed a negative correlation with the pre-dilation diameter of the strictures ( r = - 0.92, P < 0.01). Thinner strictures required more dilations before symptomatic relief was achieved. In addition, the stricture length in group B (5.4 +/- 3.4 cm) was significantly longer than that in group A (2.6 +/- 1.1 cm) ( P = 0.009). The overall success rate was 88 % (22 of 25), including 100 % in the 21 patients with a stricture length of less than 8 cm and 25 % in the four patients with a stricture length more than 8 cm ( P = 0.02). CONCLUSIONS: CRE balloon dilation without fluoroscopy is an effective treatment for esophageal strictures less than 8 cm in length. Pre-dilation diameter and stricture length are factors that influence the numbers of dilations required and the need for additional dilations.

Fatal hepatic failure after emergence of the hepatitis B virus mutant during lamivudine therapy in a patient with liver cirrhosis.

Lamivudine therapy for chronic hepatitis and decompensated liver cirrhosis related to the hepatitis B virus (HBV) resulted in improvement of liver function and inhibition of viral replication. Despite emergence of the HBV mutant, e-antigen seroconversion and improvement of liver function may be achieved with continuation of lamivudine therapy. Although hepatic decompensation has been reported in a few cases after the emergence of lamivudine-resistant mutants, fatal cases of non-transplant patients have only rarely been reported in the literature. Here, we describe a patient with HBV-related liver cirrhosis who died after a breakthrough infection with a lamivudine-resistant mutant. Hepatic failure and mortality developed after flare-up of severe hepatitis after 13 months of lamivudine treatment. Emergence of the HBV mutant with substitution of isoleucine for leucine at residue 426 (L4261) in combination with isoleucine for methionine at residue 550 (M5501) was observed at 10 and 13 months of treatment.

Chronic opioid treatment may uncouple opioid receptors and G-proteins: evidence from radiation inactivation analysis.

Radiation inactivation (target size analysis) was used in this study to determine whether uncoupling of opioid receptor and G-protein is a contributing mechanism to opioid tolerance. Male Sprague-Dawley rats (160-260 g) were rendered tolerant to morphine or [D-Ala2,D-Leu5]enkephalin (DADLE) by multiple i.p. or i.c.v. injections twice a day for 6 or 5 days. Control rats were injected with saline instead of opioids. The animals were killed, the midbrains excised and pooled together for each group. The washed P2 membranes were suspended in buffer and irradiated with 1-10 Mrad doses of 60Co irradiation, following which mu- or delta-opioid receptor binding activity of each sample was assayed. The molecular weight of the receptor was calculated from a standard irradiation curve constructed using several enzyme markers of known molecular weight. We found that the functional molecular size of mu-opioid receptor significantly decreased from 349 kDa to 228 kDa after 6 days of chronic morphine treatment, while, the molecular size of delta-opioid receptor decreased from 303 kDa to 223 kDa after 5 days of chronic DADLE treatment. These results are consistent with the uncoupling of opioid receptor from G-protein during chronic opioid treatment.

[Efficiency of patient-controlled analgesia versus conventional analgesia in patients after thoracotomy].

The patients received thoracotomy usually suffered from significant severe pain postoperatively, which accompanied with impaired pulmonary function or increased incidences of atelectasis and pneumonia. So adequate analgesia for those patients is indicated. The purpose of this study is to investigate the efficiency of patient-controlled analgesia (PCA) and determine whether it is better than conventional analgesia or not. Twenty-six patients, ASA physical status class I and II, were randomized into two groups: PCA and intramuscular (IM). The effect on pain relief was assessed by a visual analogue pain scale (VAPS) q 4 h postoperatively for two days. Forced vital capacity (FVC) and the questionnaire of nocturnal sleep disturbance by pain were evaluated preoperatively, the first, second postoperative mornings. As result of this study, the patients of PCA group get less pain than IM group after the first and second days of surgery. VAPS values are 3.7 +/- 1.1, 2.8 +/- 0.8 and 6.1 +/- 0.9, 5.3 +/- 1.1 respectively pertaining to PCA and IM groups (p less than 0.05). The patients of IM group get more disturbance of nocturnal sleep than PCA group at initial two nights of postoperation as well (p less than 0.05). It is manifest to look out the significant difference between these two groups in accordance with FVC ratio records of post-surgery vs presurgery at initial two days after surgery on the subject of respiratory function recovery. PCA group are 46.46 +/- 7.29%, 52.25 +/- 8.32% in a condition of more progress on lung function recovery than IM group of 38.13 +/- 10.25%, 42.15 +/- 7.82% (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

[Renal effect of isoflurane].

Isoflurane is a pentafluorinated methyl ether and can be metabolized to inorganic fluoride in man. Nephrotoxicity may be developed after it's administration. The present study was carried out to evaluate the effects of isoflurane on renal hemodynamic and excretory function in 15 patients. The systolic, diastolic and mean arterial pressure and renal function were measured before, during and after induction of anesthesia by isoflurane. Renal plasma flow (RPF) and glomerular filtration rate (GFR) were estimated by the clearances of paraaminohippuric acid and inulin, respectively. The results showed that a slight reduction in systolic pressure but no significant change in diastolic and mean blood pressures were found during anesthesia. There were 30% and 50% reductions in RPF and GFR, respectively. The filtration fraction increased significantly. Simultaneous decreases in urine flow, absolute and fractional excretions of sodium, absolute excretion of potassium, osmolar clearance and free water reabsorption rate were observed during isoflurane anesthesia. However, the blood pressure and renal function returned to pre-anesthesia levels 30-60 minutes after termination of anesthesia. These data suggest that isoflurane induces renal depressive effect which is reversible and temporary.

Effects of ketamine on the circulatory functions and body tissue oxygenation in dogs under normal and hypovolemic conditions.

Anesthetic induction with ketamine may cause cardiovascular (CV) stimulation and depression. The study was conducted in dogs to evaluate the dependence of ketamine-induced CV effects upon the dosage, mode of administration and experimental hypovolemic conditions. Slow ketamine infusion (n = 12) at 3 dose levels (5 mg/kg/min for 1, 2 and 4 min to a total dose of 5, 10 and 20 mg/kg) consistently increased the arterial pressure (AP) and heart rate (HR). Rapid bolus injections at 5, 10 and 20 mg/kg (n = 16) produced biphasic changes--decreases followed by increases in AP and HR. Profound depressor and bradycardic responses were readily observed with large dose, rapid bolus injection and during hemorrhagic hypotension. The striking CV depression in some cases became irreversible and led to death. Further study in 8 open-chest dogs revealed that ketamine infusion (a total dose of 10 mg/kg) caused slight increases in cardiac output (CO) and tissue oxygen uptake (VO2). However, the marked depressor response to bolus injection was associated with decreases in CO, total peripheral resistance, stroke volume and VO2. These inhibitory effects were prolonged after hemorrhagic hypotension. In a few cases, CO and VO2 became severely and progressively depressed and death ensued shortly following the injection.