Combined UGT1A1 and UGT1A7 variant alleles are associated with increased risk of Gilbert's syndrome in Taiwanese adults.

Gilbert's syndrome (GS) is caused by a reduction in the activity of hepatic bilirubin UDP-glucuronosyltransferase (UGT). This reduction is associated with UGT1A1*28 and UGT1A1*6 polymorphisms. Recent research also showed that carriage of UGT1A1*6 allele were significantly related with UGT1A7*3. Polymerase chain reaction-restriction fragment length polymorphism were utilized to determine UGT1A7 and UGT1A1 genes for 207 patients with GS and 207 gender/age-matched healthy controls. For the 207 healthy controls, linkage disequilibrium was observed between -57UGT1A7 and 622UGT1A7 loci (D' = 1.00 and r(2) = 1.00), -57UGT1A7 and 211UGT1A1 loci (D' = 0.72 and r(2) = 0.36), respectively. A dose-response effect for number of at-risk allele of UGT1A1 and risk for GS was noted (odds ratio (OR) = 8.19 for heterozygous UGT1A1*28 genotype; OR = 124.96 for homozygous UGT1A1*28 genotype; and p for trend <0.05). Patients with combined genotypes carrying UGT1A7 variant alleles and UGT1A1 variant alleles (including UGT1A1*28 and UGT1A1*6) are associated with increased risk of GS (OR = 13.96 for patients with combined genotype carrying at least one variant allele of UGT1A1 and UGT1A7). In conclusion, the -57UGT1A7 (T>G) is highly associated with UGT1A7*3 and moderately associated with 211UGT1A1 (G>A). Certain UGT1A1/UGT1A7 combined genotypes are risk factors of GS.

A viable secondary intra-abdominal pregnancy resulting from rupture of uterine scar: role of MRI.

Pre-natal diagnosis of intra-abdominal pregnancy is difficult. Ultrasound has been the frontline modality to date; however, it gives a diagnostic error of 50-90% and its use is disappointing. In recent years, MRI has emerged as an appealing imaging modality. With its good soft tissue contrast and non-ionizing property, it acts as a means of definitive non-invasive assessment before surgical intervention when ultrasound is inconclusive.

Successful initial treatment with weekly etoposide, epirubicin, cisplatin, 5-fluorouracil and leucovorin chemotherapy in advanced gastric cancer patients with disseminated intravascular coagulation.

BACKGROUND: Acute disseminated intravascular coagulation (DIC) is a rare but severe complication of gastric adenocarcinoma. Conventional treatments, such as fresh frozen plasma, platelet replacement and heparin injections, are disappointing. The only way to correct this fatal condition is to control the underlying cancer promptly by effective chemotherapy. Here the successful initial control of acute DIC in gastric cancer patients with weekly EEPFL chemotherapy is reported. METHODS: Advanced gastric cancer patients complicated with acute DIC were eligible. Patients were treated with weekly EEPFL therapy (etoposide 40, epirubicin 10, cisplatin 25, 5-fluorouracil 2200 and leucovorin 120 mg/m2 ). Response, survival and toxicity were evaluated. RESULTS: From April 1997 to April 1999, six patients were included in this study. All patients received EEPFL chemotherapy. Clinical and laboratory evidence of acute DIC stabilized quickly after starting chemotherapy. Four patients showed a partial response, one stable disease and one progressive disease. The toxicity was mild and well tolerated. Median survival was 28 weeks (12, 14, 26, 30, 30 and 32 weeks). All patients suffered from a relapse of DIC after initial successful control and died within 30 days of clinical and laboratory evidence of acute DIC relapse. CONCLUSION: EEPFL therapy is an effective chemotherapy regimen for patients with advanced gastric cancer associated with acute DIC. The prognosis is poor if the DIC relapses after the initial successful control.

Supercritical fluid extraction and clean-up of organochlorine pesticides in Chinese herbal medicine.

A method involving the simultaneous extraction and clean-up of 13 organochlorine pesticides (OCPs) from Chinese herbal medicines (CHMs) was developed using supercritical fluid extraction (SFE) followed by gas chromatography-electron capture detection and mass spectrometric confirmation. The pesticides in the study consisted of alpha-, beta-, gamma-, and delta-benzene hexachloride, heptachlor, aldrin, heptachlor epoxide, endosulfan I, 4,4'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethene), dieldrin, endrin, 4,4'-DDD (1,1-dichloro-2,2-bis(p-chlorophenyl)ethane), endosulfan II, 4,4'-DDT (2,2-bis(p-chlorophenyl)1,1,1-trichloroethane), endrin aldehyde, and endosulfan sulfate. A series of experiments was conducted to optimize the final extraction conditions [pure CO2, 250 atm extraction pressure (1 atm = 101,325 Pa), 50 degrees C extraction temperature, 5 min static extraction time, 20 min dynamic extraction time, 2.0-g Florisil sorbent on top of 0.1-g samples, 12-ml n-hexane eluting at 1 ml/min, and a 10-ml extraction vessel]. Florisil sorbent was placed with the sample in the SFE vessel to provide a facile and effective clean-up approach. Mean recoveries of 78-121% with reproducibilities of 5-31% were obtained for the pesticides except for endosulfan II, endosulfan sulfate and endrin aldehyde. The simple and rapid method may be used to determine OCPs in CHMs routinely, and in fact, was used to analyze CHMs sold in Taiwan.

Molecular characterization of germline mutations in neurofibromatosis 2 in two families.

Neurofibromatosis 2 (NF2) is an autosomal dominant disorder that predisposes patients to central nervous system tumors. It is caused by mutations in the NF2 tumor suppressor gene, which is located on chromosome 22q12. We studied 2 multigenerational NF2 families (three members of family 1 and the proband of the family) by gene mutation analysis and clinical assessment. One member of family 1 had a 169 C-->T point mutation at codon 57 of exon 2 and had a severe phenotype. His father had a silent 1113 C-->T point mutation at codon 371 of exon 11 and had a normal phenotype. The proband of family 2 had a deletion at nucleotide 720 G (codon 240) of exon 8. This led to a frameshift and termination at codon 250, and a severe NF2 phenotype. Our results indicate that clinical abnormalities can be present in carriers. Nonsense and frameshift mutations in the NF2 tumor suppressor gene are associated with phenotypes. The clinical abnormalities can develop at a young age.

Supercritical fluid extraction and clean-up of organochlorine pesticides and polychlorinated biphenyls in mussels.

The simultaneous extraction and clean-up of mussel samples followed by gas chromatography with electron-capture detection and mass spectrometric confirmation of 15 organochlorine pesticides (OCPs) and 11 polychlorinated biphenyls (PCBs) is developed using Florisil sorbent in the supercritical fluid extraction cell. The method detection limits vary from 1 to 10 ng/g for OCPs and from 2 to 15 ng/g for PCBs. Mean reproducibilities of 11% and 10% and mean recoveries of 80% and 53%, respectively, for OCPs and PCBs are obtained. The feasibility of the proposed supercritical fluid extraction method was confirmed by analyzing a certified reference material and mussels collected from Taiwan region. The method is simple, rapid and requires only small amounts of samples and solvents. It may serve as a screening protocol for the determination of OCPs and PCBs in mussels on a routine basis.

Phase II study of flutamide in the treatment of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a male predominant disease and may be an androgen-dependent or androgen-responsive tumor. This Phase 11 study was designed to investigate the clinical activity and toxicity of flutamide in the treatment of patients with advanced HCC. METHODS: Thirty-two patients with measurable advanced HCC were studied. Flutamide, 750 mg per day, was administered orally for 8 weeks. Ten patients died before repeat tumor measurements could be performed. RESULTS: Twenty-two patients were evaluable for response and toxicities. There were no complete responses nor partial responses. Nine of 22 patients (41%) had stable disease and 13 patients (59%) had progressive disease. Serum alpha-fetoprotein was reduced in three patients. The median survival was 10 weeks (range, one to 35 weeks). Toxicities were minimal and tolerable. CONCLUSIONS: Flutamide is not effective in the treatment of advanced HCC. Clinically, HCC may not be an androgen-responsive tumor. Other new methods of treatment of HCC warrants future clinical investigations.

Phase II study of mitoxantrone in unresectable primary hepatocellular carcinoma following hepatitis B infection.

A total of 20 patients with histologically proven primary hepatocellular carcinoma (PHC) received mitoxantrone IV at a dose of 10-16 mg/m2 every 3 weeks. All patients had previous hepatitis B infection. None underwent remission after treatment; 2 had stable disease and 18 progressive disease. The median overall survival was 13 weeks (range, 1-59 weeks). There was no evidence of significant antitumor activity for mitoxantrone in our patients with PHC. Hematotoxicity occurred in 100% of the patients with grades 2-4 leukopenia, 89% of those with grades 1-4 anemia, and 26% of those with grades 2-3 thrombocytopenia. Cardiotoxicity occurred in 20% of the patients after 14-30 mg/m2 mitoxantrone; these included complete heart block with fatal outcome in one case, decreased ventricular ejection fraction in one, and sinus tachycardia in two. Nausea, vomiting, fever, diarrhea, and alopecia were mild and occurred in 15%-45% of the patients Therefore, patients with PHC following hepatitis B infection may be less tolerant to mitoxantrone, resulting in the apparent increase in toxicities.