Juvenile Alpers disease

BACKGROUND: Alpers disease is commonly associated with polymerase gamma deficiency and usually affects infants or young children. OBJECTIVE: To report a juvenile case of Alpers disease due to mutations in the polymerase gamma gene (POLG1). DESIGN: Clinical, pathologic, biochemical, and molecular analysis. SETTING: Tertiary care university hospital and academic institutions. PATIENT: A 17-year-old adolescent girl with intractable epilepsy and liver disease. MAIN OUTCOME MEASURES: Clinical course and pathologic, biochemical, and molecular features. RESULTS: Biochemical and pathologic evidence suggested a respiratory chain defect, which was confirmed by enzyme analysis of the liver. Mutational analysis of POLG1 showed 2 novel mutations: T851A and R1047W. CONCLUSION: The POLG1 mutations can cause juvenile and childhood Alpers disease.     

A novel cell permeant and far red-fluorescing DNA probe, DRAQ5, for blood cell discrimination by flow cytometry.

The deep red fluorescing agent (DRAQ5) is a synthetic anthraquinone with a high affinity for DNA and a high capacity to rapidly enter living cells or stain fixed cells. DRAQ5 is optimally excited by red-light emitting sources and yields a deep red emission spectrum which extends into the low infra-red. DRAQ5 shows excitation at sub-optimal wavelengths including the 488 nm line and the multi-line UV wavelengths emitted by argon-ion lasers. Single beam (488 nm) flow cytometry has been used to demonstrate the utility of DRAQ5-nuclear DNA fluorescence as a discriminating parameter for human leucocytes and lymphoma cells, in combination with fluorochrome-labelled antibodies for the detection of surface antigens and subpopulation recognition. DRAQ5 fluorescence was found to reflect cellular DNA content as evidenced by cell cycle distribution profiles for asynchronous and cell cycle-perturbed populations. Importantly, DRAQ5 can be used in combination with FITC and RPE-labelled antibodies, without the need for fluorescence compensation.     

A nationwide population-based study of migraine in Brazil

The aim of this study was to estimate the 1-year prevalence of migraine and the degree of the association of migraine with some sociodemographic characteristics of a representative sample of the adult population of Brazil. This was a cross-sectional, population-based study. Telephone interviews were conducted on 3848 people, aged 18–79 years, randomly selected from the 27 States of Brazil. The estimated 1-year gender- and age-adjusted prevalence of migraine was 15.2%. Migraine was 2.2 times more prevalent in women, 1.5 times more in subjects with > 11 years of education, 1.59 times more in subjects with income of < 5 Brazilian Minimum Wages per month, and 1.43 times more in those who do not do any physical exercise. The overall prevalence of migraine in Brazil is 15.2%. Migraine is significantly more prevalent in women, subjects with higher education, with lower income, and those who do not exercise regularly, independently of their body mass index.     

Visual identification of bacterially contaminated red cells

There have been increasing numbers of reports of transfusion-acquired Yersinia enterocolitica bacteremia (including several fatal cases). Fifteen units of whole blood were inoculated with various concentrations of Y. enterocolitica serotype 0:3 and processed into AS-3 preserved red cells (RBCs). Consistent growth of the organism was found at inoculum concentrations greater than or equal to 10 colony-forming units per mL. In all 13 units of RBCs that supported the growth of Y. enterocolitica, a darkening in color (due to hemolysis and a decrease in pO2) was observed in the bag. The attached sample segments, which were sealed from the main unit, remained sterile and did not darken. This color change was apparent in all the contaminated units by Day 35, which was 1.5 to 2 weeks after the bacteria were first detected in cultures of the blood. Hence, by comparison of the color of the segment tubing with that of the unit itself, units grossly contaminated with Y. enterocolitica can be identified prior to transfusion. Moreover, review of photographs on file at the Centers for Disease Control revealed this dramatic color change in 2 units of blood that caused transfusion-transmitted sepsis (Enterobacter agglomerans and an unidentified gram-negative bacillus, not Yersinia sp.), which demonstrated that the color change was not limited to Y. enterocolitica. This method of visual identification of contaminated units of blood could decrease the incidence of posttransfusion bacterial sepsis.     

Prolonged survival in a patient with choroidal metastases from urothelial bladder cancer

Choroidal metastases secondary to urothelial carcinoma are extremely rare and are usually associated with an extremely poor prognosis. We present a case of an 88-year-old man with newly diagnosed urothelial carcinoma of the bladder who presented with acute loss of vision before commencing definitive concurrent chemoradiotherapy to the bladder. Ophthalmological examination demonstrated bilateral choroidal metastases. He received palliative radiotherapy to the orbits and completed his planned radiotherapy to the bladder. He remained disease-free at last follow-up 4 years after the completion of treatment. We review the literature particularly with regard to diagnosis and management of choroidal metastases. Choroidal metastases should be considered in a patient with a history of urothelial cancer presenting with new onset of eye symptoms.     

A Toxicological Basis to Derive a Generic Interspecies Uncertainty Factor.

A new method is proposed to derive the size of the interspecies uncertainty factor (UF) that is toxicologically and statistically based. The method involves quantifying interspecies variation in susceptibility to numerous toxic substances via the use of binary interspecies comparisons that are converted to a 95% UF. This interspecies UF represents an estimate of the upper 95% of the population of 95% prediction intervals (PI) for binary interspecies comparisons within four categories of phylogenetic relatedness (species within genus, genera within family, families within order, orders within class). The 95% interspecies UFs range from a low of 10 for species within genus up to 65 for orders within class. Most mammalian toxicology studies involving mice, rats, cats, dogs, gerbils, and rabbits are orders-within- class categories for human risk assessment and would be provided a 65-fold UF. Larger or smaller interspecies UF values could be selected on the level of protection desired.     

商陆多糖Ⅰ联合白细胞介素2对小鼠脾细胞杀瘤活性的影响

商陆多糖Ⅰ(PAP-I),0.3～3μg·ml^-1和小鼠脾细胞培养3～5d可显著增强其杀伤P815肿瘤细胞活性及IL-2(250～500IU·ml^-1)诱导的LAK细胞活性,最适浓度为1μg·ml^-1。PAP-I及IL-2和脾细胞培养的上清液对P815肿瘤细胞无细胞毒作用,但能增强脾细胞及LAK细胞杀瘤活性。PAP-I,5,10及50mg·kg-1,ip可增强脾细胞杀伤P₈₁₅和L₉₂₉细胞的活性及IL-2诱导的LAK细胞活性。     

A meta-analysis on depression and subsequent cancer risk

Background

The authors tested the hypothesis that depression is a possible factor influencing the course of cancer by reviewing prospective epidemiological studies and calculating summary relative risks.

Methods

Studies were identified by computerized searches of Medline, Embase and PsycINFO. as well as manual searches of reference lists of selected publications. Inclusion criteria were cohort design, population-based sample, structured measurement of depression and outcome of cancer known for depressed and non-depressed subjects

Results

Thirteen eligible studies were identified. Based on eight studies with complete crude data on overall cancer, our summary relative risk (95% confidence interval) was 1.19 (1.06–1.32). After adjustment for confounders we pooled a summary relative risk of 1.12 (0.99–1.26).No significant association was found between depression and subsequent breast cancer risk, based on seven heterogeneous studies, with or without adjustment for possible confounders. Subgroup analysis of studies with a follow-up of ten years or more, however, resulted in a statistically significant summary relative risk of 2.50 (1.06–5.91).No significant associations were found for lung, colon or prostate cancer.

Conclusion

This review suggests a tendency towards a small and marginally significant association between depression and subsequent overall cancer risk and towards a stronger increase of breast cancer risk emerging many years after a previous depression.

     

The unstable Hb Genova (beta 28Leu replaced by Pro) in an East African Family. Family study and the effect of splenectomy.

A fifth family with the unstable Hb Genova is reported from Kenya, East Africa. This almost certainly represents an independent mutation. The beneficial effect of splenectomy has been carefully assessed in one member of the family.