Diagnostic role of an immunoassay-detected polymorphism of factor IX for potential carriers of hemophilia B

In hemophilia B, assays based on a monoclonal antifactor IX specific for the Thr-148 variant of an exonic polymorphism have diagnosed carriers in selected families by either establishing linkage or by indicating the presence or absence of a given normal factor IX. The sensitivity of the immunoassays for detecting heterozygous women was explored by comparing results from immunoassays with solid-phase polyclonal v the monoclonal antifactor IXs. Factor IX with the normal Ala-148 variant gave a flat dilution curve, qualitatively distinct from factor IX with the Thr-148 variant in the monoclonal assay. The two were indistinguishable in the polyclonal assay. Mixtures of equal amounts of the two types gave an intermediate result, about half as reactive in the monoclonal as compared with the polyclonal assay system. Whereas mixtures with 10% Ala-148 and 90% Thr-148 factor IXs could not readily be distinguished from Thr-148 factor IX plasma, as little as 1% of the Thr-148 protein was detected in Ala-148 factor IX plasma. The frequency of the Ala-148 variant varied in individuals with different ethnic backgrounds; it was found in 29% of white, 12% of black, and none of Asian blood donors' factor IX genes in Seattle. Only 4% of samples from South African black men were nonreactive (ie, Ala- 148). The Thr/Ala-148 dimorphism is in strong linkage disequilibrium with Taql restriction fragment length polymorphisms (RFLPs). Three recombinations were noted in normal white genes and one in a normal black factor IX gene (less than 2% of those examined). In 34 white families with at least one woman being a possible carrier, genetically, the immunoassay results were informative in 18. RFLP analyses were informative in eight of the 15 families tested. In five families each, assignment of carrier status was made to a woman by only DNA or only immunoassay results, whereas the other approach was noninformative. The immunoassays provide a rapid, inexpensive screening test and complement DNA analysis in white women who are potential carriers of hemophilia B.     

Distress due to unwanted side-effects of prostate cancer treatment is related to impaired well-being (quality of life)

Based on traditional quality of life scales, it has been suggested that known side-effects of prostate cancer treatment do not influence the quality of life. The present authors have developed an alternative approach to quality of life assessment applying epidemiological methods. Using a self administered questionnaire, we investigated 431 prostate cancer patients and an age stratified sample of 435 randomly selected men. Patients reporting any level of distress due to waning sexual functions (66%) or urine or bowel symptoms (38%), reported a lower psychological well-being compared to patients not reporting these symptoms or patients not distressed by their symptoms. Our results stress that an intact sexual and urinary and bowel functions are important for the quality of life among elderly men with or without prostate cancer.     

Combination of ECMO and cytokine adsorption therapy for severe sepsis with cardiogenic shock and ARDS due to Panton–Valentine leukocidin—positive <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> pneumonia and H1N1

Sepsis-induced cardiogenic shock in combination with severe acute respiratory failure represents a life-threatening combination that is often refractory to the conventional methods of treatment. We describe the case of a 33-year-old patient who developed acute cardiovascular collapse and ARDS secondary to superinfection of Panton–Valentine leukocidin—positive Staphylococcus aureus and H1N1 pneumonia who underwent successful combination therapy for severe sepsis-related cardiomyopathy and respiratory failure using extracorporeal membrane oxygenation and cytokine adsorption therapy.     

A mathematical model of optimized radioiodine-131 therapy of Graves' hyperthyroidism

Background

The current status of radioiodine-131 (RaI) dosimetry for Graves' hyperthyroidism is not clear. Recurrent hyperthyroidism and iatrogenic hypothyroidism are two problems which interact such that trying to solve one leads to exacerbation of the other. Optimized RaI therapy has therefore begun to be defined just in terms of early hypothyroidism (ablative therapy) as physicians have given up on reducing hypothyroidism.

Methods

Optimized therapy is evaluated both in terms of the greatest separation of cure rate from hypothyroidism rate (non-ablative therapy) or in terms of early hypothyroidism (ablative therapy) by mathematical modeling of outcome after radioiodine and critically discussing the three common methods of RaI dosing for Graves' disease.

Results

Cure follows a logarithmic relationship to activity administered or absorbed dose, while hypothyroidism follows a linear relationship. The effect of including or omitting factors in the calculation of the administered I–131 activity such as the measured thyroid uptake and effective half-life of RaI or giving extra compensation for gland size is discussed.

Conclusions

Very little benefit can be gained by employing complicated methods of RaI dose selection for non-ablative therapy since the standard activity model shows the best potential for cure and prolonged euthyroidism. For ablative therapy, a standard MBq/g dosing provides the best outcome in terms of cure and early hypothyroidism.     

Formulation and characterisation of Bordetella pertussis fimbriae as novel carrier proteins for Hib conjugate vaccines

Haemophilus influenzae type b (Hib) capsular polysaccharide (polyribosylribitol phosphate, PRP) is the active component of conjugate vaccines that have proven successful in preventing invasive Hib disease. Conjugation of PRP to a protein carrier greatly improves its immunogenicity providing protection in infants and subsequent antibody maturation upon boosting. In this study, fimbriae isolated from Bordetella pertussis have been assessed as novel carrier proteins. These proteins are components of some acellular pertussis vaccines and clinical trials have indicated that fimbriae could be important protective antigens against whooping cough. Fimbriae (Fim2 and Fim3) purified from B. pertussis were dissociated in 6 M guanidine hydrochloride, pH 10.5, to produce proteins of defined size and to facilitate the production and characterisation of the conjugates. Both carbodiimide-mediated coupling and reductive amination were used to conjugate PRP to dissociated fimbriae. Efficiency of conjugation was determined by size exclusion chromatography followed by protein and polysaccharide analysis of fractionated components. Immunisation of rabbits with dissociated fimbriae-PRP conjugates (D.fim-PRP) produced high anti-fimbrial and anti-PRP IgG titres. Use of a D.fim-PRP conjugate could protect against Hib disease and may also augment protection against B. pertussis.     

Complementary medicine: use and attitudes among GPs

BACKGROUND: Information about use and attitudes of GPs towards complementary medicine is required in order to inform the debate about its place within mainstream medicine. There is evidence that public use of complementary medicine is particularly high in the South-West of England. OBJECTIVE: This study aimed to determine the use of, and attitudes towards, complementary medicine among GPs. METHODS: A questionnaire survey was performed of all primary care physicians working in the health service in Devon and Cornwall. RESULTS: Replies were received from 461 GPs, a response rate of 47%. A total of 314 GPs (68%, range 32-85%) had been involved in complementary medicine in some way during the previous week. One or other form of complementary medicine was practised by 74 of the respondents (16%), the two most common being homoeopathy (5.9%) and acupuncture (4.3%). In addition, 115 of the respondents (25%) had referred at least one patient to a complementary therapist in the previous week, and 253 (55%) had endorsed or recommended treatment with complementary medicine. Chiropractic, acupuncture and osteopathy were rated as the three most effective therapies, and the majority of respondents believed that these three therapies should be funded by the health service. A total of 176 (38%) of respondents reported adverse effects, most commonly after manipulation. CONCLUSION: Over two-thirds of the GPs in Devon and Cornwall who responded to the survey had been involved with complementary medicine in some way during the previous week. This figure is higher than the national average. The majority of respondents believed that acupuncture, chiropractic and osteopathy were effective and should be funded by the NHS.      

薄层扫描法测定熊胆引流物中胆汁酸含量

熊胆向以贵重药材闻名,被称之为稀有药品,为开发熊胆资源,解决熊胆奇缺问题,我校解剖教研室已成功地完成了人工引流熊胆汁技术,可随时进行人工引流获取熊胆汁。为了确定胆汁的质量指标,了解其主要成分,我们进行了引流胆汁与天然熊胆的分析。文献报道,熊胆中主要含熊去氧胆酸(ursodesoxycholic acid,UDCA)、鹅去氧胆酸(cheno desoxycholic acid,CDCA)、胆酸(cholic acid,CA)、去氧胆酸(deoxycholic,acid DCA)等。