Racial difference in bioavailability of oral ibandronate between Caucasian and Taiwanese postmenopausal women.

Following 150 mg of oral ibandronate, Taiwanese females have greater serum and urine levels of this drug and bone resorption marker suppression than Caucasian women. These inter-ethnic differences seems to be partly explained by a 2.48-fold higher bioavailability of ibandronate in Taiwanese postmenopausal women. INTRODUCTION: Interethnic differences in the pharmacokinetics of oral ibandronate for osteoporosis are unknown. We compared the disposition of oral ibandronate between Caucasian and Taiwanese postmenopausal women. METHODS: Ibandronate 150 mg was administered to 35 Caucasian and 16 Taiwanese postmenopausal women in two separate phase 1 studies. Interethnic comparisons were performed to assess pharmacokinetic properties, including the area under the concentration-time curve (AUC), peak concentration (Cmax), elimination half-life, urinary drug recovery (Ae%), renal clearance (CLr), apparent total clearance (CL/F), and apparent volume of distribution (Vd/F). RESULTS: The mean AUC, Cmax, and Ae% were 2.41-, 1.69-, and 2.95-fold greater in the Taiwanese than in the Caucasian subjects, and the average CL/F and Vd/F were 2.48- and 2.46-fold smaller. There were no significant differences in mean CLr and half-life between both groups. As bisphosphonates are not biotransformed but are mainly excreted in the urine, the total body clearance is close to the CLr. These results suggested a larger bioavailability in the Taiwanese group which resulted in the differences in the CL/F and Vd/F. Multiple linear regression analysis demonstrated ethnicity influences of the pharmacokinetic properties after adjusting for the other variables. CONCLUSIONS: Bioavailability was largely responsible for the interethnic pharmacokinetic differences following oral administration of 150 mg ibandronate and seemed greater in the Taiwanese compared with the Caucasian subjects. Further dose-ranging studies are warranted to determine the optimal dosages of oral ibandronate in patients of Asian or Taiwanese ethnicity.

Sunitinib-induced hyperammonaemia in a patient with pancreatic neuroendocrine tumour.

WHAT IS KNOWN AND OBJECTIVE: Sunitinib can improve progression-free survival and overall survival in patients with advanced pancreatic neuroendocrine tumor (PNET). From clinical trial, most commonly reported adverse events of sunitinib were neutropenia (12%), diarrhea (10%), asthenia (7%), erythrodysesthesia (7%), hypertension (7%) and thrombocytopenia (6%). CASE SUMMARY: We report a patient with PNET with liver metastases who developed hyperammonemia with a low dosage of sunitinib probably contributed by the presence of liver metastases. WHAT IS NEW AND CONCLUSIONS: We would like to draw attention to the potential risk of sunitinib induced hyperammonemic encephalopathy even with a low dosage of sunitinib. The absence of sunitinib-induced hyperammonemia during its initial course does not rule out this possibility if there is increased in liver metastases. We suggest checking the ammonia level if patient on sunitinib presented with altered sensorium even if the liver function is normal.

Family-based association study of cytotoxic T-lymphocyte antigen-4 with susceptibility to Graves' disease in Han population of Taiwan.

Graves' disease (GD) is a common organ-specific autoimmune disorder inherited as a complex trait. Although there has not been consensus regarding the genuine susceptibility alleles, many population-based genetic studies showed association of the cytotoxic T-lymphocyte antigen-4 (CTLA4) gene with GD. In contrast, evidence utilizing family-based studies came only from the Caucasian population. Here we performed a family-based association study in the Han population in Taiwan. We enrolled 374 affected individuals and 347 unaffected family members in 151 GD pedigrees. Four single-nucleotide polymorphisms (SNP) and a short tandem repeat polymorphism (STRP) at CTLA4 were genotyped. Association of GD with a novel risk SNP at the 5' upstream region, CTLA4_-1722_T/C (rs733618), was demonstrated (P=0.0096). We also replicated the association signal of a coding SNP, CTLA4_+49_G/A (rs231775, P=0.0219). A common haplotype composed of CTLA4_-1722_T/C and CTLA4_(AT)n (an STRP marker: UniSTS:48500) showed protective effect (P=0.0004). Our results of family-based association study, taken together with those from the Caucasian population, provide evidence that CTLA4 confers susceptibility to GD across different ethnic backgrounds.

Surgical treatment of parastomal hernia complicating sigmoid colostomies.

PURPOSE: Parastomal hernia is a common late complication of colostomy. Surgical approach to the repair of parastomal hernia is controversial. Results of surgical treatment are disappointing. The aim of this study was to assess the outcome of surgical treatment of parastomal hernia. METHOD: This article reports a retrospective review of those patients who had undergone a surgical treatment of parastomal hernia complicating sigmoid colostomy. The indications, surgical procedures, complications, and outcome were carefully studied. RESULTS: There were 43 surgical treatments of parastomal hernia. Sixteen underwent simple local repair; 25 stomas were relocated, and 2 were locally repaired with mesh. Overall recurrence was 18 of 40 (45 percent). Recurrences for fascial repair and stoma relocation were 6 of 13 (46 percent) and 10 of 25 (40 percent), respectively. Stoma relocation could be accomplished without formal laparotomy in 19 of 25 cases. Incisional hernia occurred in only 2 of these 25 relocations. CONCLUSION: Fascial repair alone can be performed for symptomatic small hernias because of its advantage of minimal morbidity. Stoma relocation without formal laparotomy can be advocated for larger hernias. A combination of local resite together with mesh reinforcement may be the alternative for further improvement of results.

A home made rapid urease test in the diagnosis of Helicobacter pylori infection.

AIM OF STUDY: To determine whether a homemade rapid urease test (RUT) (1 mL of 10% urea broth in distilled water plus one drop of 1% phenol red as indicator, cost/test USD0.19) was reliable when compared to histology in the diagnosis of HP infection. METHOD: Prospective consecutive sampling of patients who underwent outpatient oesophagogastroduodenoscopy and antral biopsies from October 1996 to January 1997. RUT and histology examinations were done on all specimens. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the RUT were calculated accordingly. RESULTS: Amongst our 140 patients, the sensitivity, specificity, positive and negative predictive values and accuracy of RUT were 94%, 99%, 99%, 95% and 96% respectively. Seventy-seven percent of the positive RUTs can be detected within 1 hour. CONCLUSION: Our homemade RUT is an inexpensive test with good sensitivity and specificity for HP infection.

Properties of the poly(vinyl alcohol)/chitosan blend and its effect on the culture of fibroblast in vitro.

In this work, the properties of poly(vinyl alcohol) (PVA) and PVA/chitosan blended membranes were investigated by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and electron spectroscopy for chemical analysis (ESCA). The SEM photographs show the PVA/chitosan blended membrane undergoes dramatic changes on the surface and bulk structure during the membrane formation. The DSC analysis shows that PVA and chitosan are not very compatible in the PVA/chitosan blended membrane, whereas the combination of two polymer chains of constitutionally different features is revealed. In addition, the surface of the PVA/chitosan blended membrane is enriched with nitrogen atoms at the ESCA analysis. These reflect the PVA membrane can be modified by blending with chitosan that in turn may affect the biocompatibility of the blended membrane. Therefore, adhesion and growth of fibroblasts on the PVA as well as PVA/chitosan blended membranes were investigated. Cell morphologies on the membranes were examined by SEM and cell viability was studied using MTT assay. It was observed that the PVA/chitosan blended membrane was more favorable for the cell culture than the pure PVA membrane. Cells cultured on the PVA/chitosan blended membrane had good spreading, cytoplasm webbing and flattening and were more compacting than on the pure PVA membrane. Consequently, the PVA/chitosan blended membrane may spatially mediate cellular response that can promote cell attachment and growth, indicating the PVA/chitosan blended membrane should be useful as a biomaterial for cell culture.

Audit of laparoscopic cholecystectomy in a single center.

A continuous audit is required to ensure laparoscopic cholecystectomy (LC) is performed safely in the surgical community in general. A retrospective review of all LC done in a single center was performed. A total of 1,244 LC were attempted. The conversion rate was 12.4%, the complication rate 3.5%, and the bile duct injury rate 0.4%. Forty percent of bile duct injury occurred after conversion. A decreasing trend of complication rate was seen in the early part of the series, then the rate steadied at about 2.5-3%. A higher threshold of conversion may not increase the bile duct injury rate. However, good laparoscopic technique and adequate experience are prerequisites to safe LC.

The investigation and management of thyroid nodules--a retrospective review of 183 cases.

The management of the patient with a thyroid nodule remains a clinical challenge because of its risk of malignancy. This is a retrospective audit of 183 patients undergoing thyroidectomy for thyroid nodules at the Queen Elizabeth Hospital, Hong Kong, in 1994. The history, physical examination and investigations done were charted and analysed against the final histopathology of the specimens. Age, sex, symptom duration and nodularity were not associated with malignancy statistically, whereas a nodule hard in consistency was shown to be associated with malignancy (P < 0.05). The sensitivity and specificity of ultrasonography, radionuclide scan and fine-needle aspiration cytology (FNAC) were 71% and 57%, 50% and 43%, and 93% and 60%, respectively. Hence, history and physical examination are unreliable for detecting malignant thyroid nodules and FNAC is mandatory. FNAC is superior to ultrasonography or radionuclide scan for evaluating thyroid nodules and should be used as the initial investigation.

Comparison of serum protein removal in haemodialysis therapy by partly protein-permeable haemodialysers.

Partly protein-permeable haemodialysers were evaluated during haemodialysis therapy for removal of serum low-molecular-mass proteins (10,000-76,000) in patients with chronic renal failure. The six haemodialyser membranes used were cuproammonium rayon (CL-S12W), cellulose acetate (Duo-Flux HP and FF-22), ethylene-vinyl alcohol copolymer (KF-101-15), polyacrylonitrile (H12-2400S) and polymethyl methacrylate (BK2.0H). The analysis was carried out by gel permeation chromatography, sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and two-dimensional gel electrophoresis (2-DE). The removal of ten serum proteins per haemodialysis therapy was also carried out by the immunodiffusion method. The protein removal in each haemodialyser is qualitatively comparable to that obtained by SDS-PAGE and 2-DE. beta 2-Microglobulin in the haemodialysate obtained with BK2.0H was removed to a lesser extent than that from the other haemodialysers, which seems to be the reason for its adsorption in the BK2.0H haemodialyser, which contains a polymethyl methacrylate membrane. The amount of serum protein excretion during haemodiafiltration treatment using the partly protein-permeable haemodialysers decreased in the order KF-101-15C greater than BK2.0H greater than CL-S12W greater than Duo-Flux HP greater than FF-22 greater than H12-2400S.

The 14-MeV neutron activation analysis of Chinese medicines for protein, phosphorus, potassium and magnesium contents (II).

Elementary form of nitrogen (protein), phosphorus, potassium and magnesium contained in 180 different kinds of Chinese medicines are analyzed by means of 14-MeV neutron activation technique. The percent contents of these elements in the Chinese medicines range from 0 to 34.41% (average: 11.73%) for protein, from 0.03 to 37.42% (average: 1.72%) for phosphorus, from 0.12 to 33.22% (average: 2.94%) for potassium and 0.03 to 5.62% (average: 0.43%) for magnesium. Comparison of the present results with the previous measurements for another 66 kinds of Chinese medicines is made.

The 14-MeV neutron activation analysis of Chinese medicines for protein, phosphorus, potassium and magnesium contents.

Elementary form of nitrogen (protein), phosphorus, potassium and magnesium contained in sixty-six different kinds of Chinese medicines were analyzed by means of 14-MeV neutron activation technique. The % contents of these elements in Chinese medicines range from 4.1 to 38.6% (average: 12.7%) for protein, 0.1 to 10.5% (average: 1.3%) for phosphorus, 1.6 to 13.8% (average 4.5%) for potassium and 0.1 to 2.5% (average: 0.5%) for magnesium. The procedure proves to be quite precise and potentially quite accurate, while only requiring about 20 minutes per sample. The methods of determining the elements are described.