Mutations of the flavin-containing monooxygenase gene (FMO3) cause trimethylaminuria, a defect in detoxication

Individuals with the recessive condition trimethylaminuria exhibit variation in metabolic detoxication of xenobiotics by hepatic flavin- containing monooxygenases. We show here that mutations in the human flavin-containing monooxygenase isoform 3 gene ( FMO3 ) impair N - oxygenation of xenobiotics and are responsible for the trimethylaminuria phenotype. Three disease-causing mutations in nine Australian-born probands have been identified which share a particular polymorphic haplotype. Nonsense and missense mutations are associated with a severe phenotype and are also implicated in impaired metabolism of other nitrogen- and sulfur-containing substrates including biogenic amines, both clinically and when mutated proteins expressed from cDNA are studied in vitro . These findings illustrate the critical role played by human FMO3 in the metabolism of xenobiotic substrates and endogenous amines.      

Differences in the process of diabetic care between south Asian and white patients in inner-city practices in Nottingham, UK

The prevalence and complication rate of diabetes is higher amongst British south Asians when compared to the rest of the adult population. There is some evidence to suggest that there are differences in access to healthcare in the UK for different ethnic groups, but there has been little research examining differences in processes of care between ethnic groups and place of delivery of diabetic care. The present study was a retrospective, multi‐practice audit exploring differences in the processes of diabetic care provided to white and south Asian patients. Data were obtained from eight practices located in deprived areas in Nottingham, UK. A review of the evidence‐based protocols for the monitoring of diabetic care generated a list of process criteria to be measured. All primary care data sources were examined over a 12‐month period by a single investigator. The data were analysed with respect to patient ethnicity and place of diabetic care after adjusting for confounders. Eight hundred and thirty‐nine diabetic patients were included in the audit and 671 (80.0%) received a formal annual diabetic review. One hundred and five (12.5%) patients were classified as south Asian. They were significantly less likely to have their blood pressure [86% versus 89%, odds ratio (OR) = 0.62, 95% confidence interval (95% CI) = 0.54–0.72] or serum creatinine (67% versus 76%, OR = 0.41, 95% CI = 0.32–0.52) measured when compared to white patients. Patients receiving shared care from a hospital‐based diabetic team were more likely to have a range of items of the annual review recorded. When examined by ethnicity, south Asians receiving shared care were again less likely than white patients to have their blood pressure and serum creatinine measured. There was also some evidence that they may be less likely to have their body mass index recorded and their feet examined. The findings of the present study showed that, although most diabetic patients received a formal annual clinical review, scope for improvement remained. Shared care of patients with a hospital‐based team produced better results when processes of care were examined. However, this benefit did not apply equally to south Asian and white patients. Further studies are indicated to confirm these results, which may have wider implications for the planning and provision of diabetic care.     

阿米福汀对单次肺照射的保护作用及TGF-β1活性的影响

目的用大鼠放射性肺损伤模式评价阿米福汀对单次肺照射的放射性肺损伤保护作用和对TGFβ1活性变化的影响。方法34只150～160g的Fish344雌性大鼠随机进入照射加药(11只)、单纯照射(11只)、单用药(6只)和正常对照(6只)实验组。用4MVX射线单次28Gy照射右全肺,照射前30min腹腔内注射阿米福汀150mg/kg。每2周观测呼吸频率和血浆转化生长因子(TGFβ1)水平,在6个月后终止观察。肺组织进行羟脯胺酸、胶原蛋白含量、总TGFβ1与活性TGFβ1水平、TGFβ1蛋白表达和巨噬细胞量等检测。结果单纯照射组呼吸频率于第8周发生改变、达(185±13)次/min,3只因呼吸困难终止观察,7只有胸腔积液;照射加药组于第14周开始增加,仅为(125±5)次/min,无呼吸困难和胸腔积液发生。单纯照射组的肺组织结构消失纤维化,照射加药组也有纤维化,但保持大部分肺泡结构。血浆TGFβ1水平呈双峰改变,单纯照射组12周时为(3.2±0.5)ng/ml,较照射加药组(1.3±0.3)ng/ml明显增高(P=0.004);肺组织活性TGFβ1与总TGFβ1含量之比分别为3.9%±0.2%与3.1%±0.2%,单纯照射明显高于照射加药组(P<0.05)。结论阿米福汀不仅能增加肺组织对放射性损伤的耐受,同时也能减少TGFβ1的含量与表达,也许同时能减少TGFβ1的活性表达。     

伊贝辛的分离和鉴定

从吉林栽培的伊贝母(Fritillaria pallidiflora Schrenk)鳞茎中分离出两种介藜芦胺类生物碱Ⅰ和Ⅱ。碱Ⅱ是一个新的甾体生物碱,定名为伊贝辛(yibeissine),结构为22,26-imino-17,23-oxidojerv-12-en-6-oxo-3β,11α-diol,碱Ⅰ是一个已知化合物,结构为11-deoxo-6-oxo-5α,6-dihydrojervine。     

Parkville virus: A novel genetic variant of human calicivirus in the Sapporo virus clade,associated with an outbreak of gastroenteritis in adults

This report describes the characterization of Parkville virus, the etiologic agent of an outbreak of foodborne gastroenteritis, that has the morphology of a calicivirus and genetic properties that distinguish it from previously identified strains in the Sapporo/Manchester virus clade. Sequence analysis of the Parkville virus genome showed it contained the RNA-dependent RNA polymerase motifs GLPSG and YGDD characteristic of members of the family Caliciviridae with an organization identical to that reported for the Manchester virus where the capsid region of the polyprotein is fused to the RNA polymerase. Parkville virus however, demonstrates considerable sequence divergence from both the Manchester and Sapporo caliciviruses, providing the first indications that genetic diversity exists within caliciviruses of this previously homogeneous clade. On the basis of recent advances in the genetic characterization of members of the family Caliciviridae, we propose a new interim phylogenetic classification system in which Parkville virus would be included with Manchester and Sapporo virus as a separate group distinct from the small round-structured viruses (Norwalk-like viruses) that also cause diarrhea in humans. J. Med. Virol. 52:173–178, 1997. © 1997 Wiley-Liss, Inc.     

Excrescent lesion: a diagnosis of lateral talar exostosis in chronically symptomatic sprained ankles.

The excrescent lesion is a symptomatic anterolateral exostosis at the insertion of the anterior talofibular ligament. It is found in patients with chronic ankle pain after inversion injuries. It is most reliably diagnosed by computed tomography scan, but physical examination and oblique radiographs are suggestive in most cases. A technique for surgical excision and, in some cases, repair of the anterior talofibular ligament is described. Five patients having a history of inversion sprains of the ankle, without significant symptomatic improvement for a mean of 21 months after the injury, were evaluated. None had significant instability in the ankle or subtalar joints, clinically or with stress radiographs. The diagnosis of excrescent lesion was confirmed with computed tomography scan in all five patients. Each underwent excision of the exostosis. Removal of the exostosis produced laxity of the anterior talofibular ligament in four of the patients and required an additional modified Brostr?m procedure to tighten the anterior talofibular ligament. Clinical results were evaluated at a mean of 33 months postoperatively, using the Ankle-Hindfoot scale from the American Orthopaedic Foot and Ankle Society. The three patients without pending claims for Workers' Compensation or related litigation all had excellent results (mean score, 93 points). Two patients with active legal claims had fair and poor results (mean score, 53 points).     

The World Health Organization initiative on noma

Oro-facial noma is a worldwide scourge in a context where the World Health Report 1998 gives a global incidence of 140,000 cases, a prevalence in 1997 of 770,000 persons surviving with heavy sequelae. The background and the five steps of the WHO oral health programme to control noma including: (i) ensuring training and awareness on early diagnosis and treatment for each public health structure, (ii) raising awareness and informing populations, (iii) promoting epidemiological research, (iv) promoting aetiological research, (v) setting up an African regional centre for the treatment of after-effects, are developed in this paper.     

Camptothecin and taxol: Discovery to clinic

Camptothecin (CPT) is a pentacyclic alkaloid isolated from wood and bark of Camptotheca acuminata. Initially it was found to be highly active in a number of mouse in vivo cancer assays. Subsequently, CPT was found to uniquely inhibit an enzyme, topoisomerase I, which is involved in DNA replication. A number of CPT analogs are in advanced clinical trial, and two, Topotecan and CPT-11, have been approved for marketing by the FDA. Taxol, a taxane alkaloid, was isolated from Taxus brevifolia. Taxol is a highly cytotoxic compound active in several mouse antitumor assays. It was subsequently found to uniquely inhibit tubulin, a protein involved in mitosis. After clinical evaluation, it has become the drug of choice for treatment of ovarian cancer. © 1998 John Wiley & Sons, Inc. Med Res Rev, 18, No. 5, 299–314, 1998.