Guidance for control of parvovirus B19 infection in healthcare settings and the community

Interventions for parvovirus B19 infection need to balance the low risk of infection at a population level with the potential for serious adverse outcome for particular groups, notably the fetus, people with haemoglobinopathies and the immunocompromised. This guidance aims to assist the local decision-making process to be as evidence-based as the available evidence allows.     

Metabolism and excretion of atorvastatin in rats and dogs.

Atorvastatin (AT) is a second-generation potent inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, clinically approved for lowering plasma cholesterol. Using a mixture of [D(5)/D(0)] AT and/or [(14)C]AT, the metabolic fate and excretion of AT were examined in rats and dogs following single and multiple oral doses. Limited biliary recycling was examined in one dog after a single dose of AT. AT-derived metabolites in bile samples were identified by metabolite screening of the [D(5)/D(0)] AT molecular clusters using tandem mass spectrometry. Bile was a major route of [(14)C] drug-derived excretion, accounting for 73 and 33% of the oral dose in the rat and dog, respectively. The remaining radioactivity was recovered in the feces; only trace amounts were excreted in urine. Radioactive components identified in rat and dog bile were the para- and ortho-hydroxy metabolites, a glucuronide conjugate of ortho-hydroxy AT, and unchanged AT. Two minor radioactive components were identified as beta-oxidation products of AT with one confirmed as a beta-oxidized AT derivative. The reappearance of AT and major metabolites in bile from a dog administered a sample of its previously excreted bile indicated biliary recycling is an important component in AT metabolism. Multiple dose administration in rats did not alter biliary metabolic profiles. Rat and dog plasma profiles after multiple dose administration were similar and showed no additional metabolites not found in bile. Examination of rat and dog bile and plasma indicates that AT primarily undergoes oxidative metabolism.     

Dorsal perilunate dislocations and fracture-dislocations: questionnaire, clinical, and radiographic evaluation

Twenty-two consecutive patients (23 wrists) underwent open reduction internal fixation of dorsal perilunate dislocations and fracture-dislocations through combined dorsal and volar approaches. One of 5 experienced wrist surgeons performed these procedures within an average of 3 days of injury (range, 0-26 days) and intercarpal fixation was kept within the proximal carpal row. Motion was instituted an average of 10 weeks (range, 5-16 weeks) after injury. All patients were males. The average age at the time of injury was 32 years (range, 16-60 years). The average follow-up period was 37 months (range, 13-65 months). Average flexion-extension motion arc and grip strength in the injured wrist were 57% and 73%, respectively, compared with the contralateral wrist. The scapholunate angle increased and the revised carpal height ratio decreased over time, which was statistically significant for both measurements. Three patients (3 wrists) required wrist arthrodesis and a fourth patient had an immediate scaphoid excision and 4-corner arthrodesis secondary to an irreparable scaphoid fracture. One patient required a proximal row carpectomy to treat septic arthritis. Nine of the remaining 18 wrists had radiographic evidence of arthritis, most often at the capitolunate or scaphocapitate articulations. Short form-36 mental summary scores were significantly greater than age- and gender-matched US population values; physical summary scores were significantly less. The disabilities of arm, shoulder, and hand evaluation, Mayo wrist score, and patient-rated wrist evaluation all reflected loss of function. Seventy-three percent of all patients had returned to full duties in their usual occupations and a total of 82% were employed.     

Combining capecitabine and gemcitabine in patients with advanced pancreatic carcinoma: a phase I/II trial.

PURPOSE: Preclinical studies indicate positive interactions between capecitabine, an oral fluorouracil precursor, and gemcitabine, the current standard treatment for advanced pancreatic carcinoma (APC). In this study, we investigated the addition of capecitabine to gemcitabine treatment for patients with APC. PATIENTS AND METHODS: This multicenter study included patients na?ve to chemotherapy who had histologically or cytologically confirmed, nonresectable or metastatic pancreatic carcinoma. Gemcitabine was given at a fixed dose of 1,000 mg/m(2) on days 1 and 8 of a 21-day cycle. Capecitabine was given in increasing doses orally bid for 14 days followed by a 1-week rest. The maximum-tolerated dose (MTD) was defined as one dose level below the dose causing dose-limiting toxicity (DLT) in >or= one third of a cohort of six patients. We included an additional 15 patients at the MTD. RESULTS: Thirty-six patients were included. DLT occurred at a dose of 800 mg/m(2) bid of capecitabine and consisted of myelotoxicity and mucositis. Hand-foot syndrome was not observed, and other toxic effects were mild. Thus, in this regimen, the recommended dose of capecitabine is 650 mg/m(2) bid. In 27 patients with measurable disease, we observed one complete and four partial remissions. In addition, significant drops (> 50% from baseline value) of the tumor marker CA 19-9 occurred in 14 of 24 assessable patients. CONCLUSION: The combination of capecitabine and gemcitabine is well tolerated, with apparent efficacy in patients with APC. Therefore, it is currently being compared with gemcitabine monotherapy in a phase III study.