Clinically significant differences between point-of-care analysers and a standard analyser for monitoring the International Normalized Ratio in oral anticoagulant therapy: a multi-instrument evaluation in a hospital outpatient setting.

The increasing number of patients requiring oral anticoagulant therapy has lead to an expansion in the use of point-of-care test (POCT) analysers for measuring the International Normalized Ratio (INR) for monitoring purposes. Availability of new technology inevitably leads to comparisons with standard methodologies, and studies to date have reached varying conclusions about the comparability of POCT INRs with conventional testing. We compared the performance of five POCT instruments (Hemochron Junior Signature, ProTime, CoaguChek S, INRatio and TAS) against Innovin thromboplastin on a Sysmex CA1500 automated analyser. The Hemochron Junior Signature, ProTime and CoaguChek S demonstrated strong correlation with the laboratory method (R2 > 0.94). These three analysers demonstrated higher percentages of paired results within 0.5 INR units (81.5, 92.0 and 74.0%, respectively); the INRatio and TAS demonstrated 54.2 and 62.2%, respectively. Within INR ranges of up to 2.0, 2.1-3.0, 3.1-4.0 and above 4.0, none of the POCT analysers demonstrated significant agreement with the standard method in every range. All POCT instruments showed a degree of bias and greater variation from the standard method at INR values above 3.0. These data indicate the potential for POCT analysers to generate INR values sufficiently different from conventional methods that they may impact on clinical decision-making.     

“Cerebral small vessel disease and other influential factors of cognitive impairment in the middle-aged: a long-term observational cohort PURE-MIND study in Poland”

GeroScience - A complex picture of factors influencing cognition is necessary to be drawn for a better understanding of the role of potentially modifiable factors in dementia. The aim was to assess...     

Alteration in the laboratory profile of a lupus anticoagulant in a patient with non-Hodgkin's lymphoma

We describe a patient with non-Hodgkin's lymphoma who developed a lupus anticoagulant (LA) detectable by activated partial thromboplastin time (APTT), dilute Russell's viper venom time (DRVVT) and kaolin clotting time (KCT). IgM anticardiolipin antibodies (ACA) were elevated. At a later admission, and following treatment for the lymphoma, routine coagulation screening showed an elevated prothrombin time (PT) without correction in mixing tests using a recombinant thromboplastin. Routine APTT was below the reference range and ACA levels were normal. Raw data for one-stage factor assays demonstrated the presence of an inhibitor. Analysis for LA was undertaken by DRVVT, KCT, activated seven lupus anticoagulant assay, Taipan snake venom time, platelet neutralisation procedures (PNP), Ecarin time and PT using rabbit brain thromboplastin. The results revealed a LA capable of prolonging the clotting times of the PNPs and PT using recombinant thromboplastin, but that was corrected using Ecarin venom, modified PNP and brain thromboplastin. The antibody also demonstrated the lupus anticoagulant co-factor effect. The factor VIII: C was markedly raised which may have masked the LA in the APTT. The changing laboratory profile over time demonstrates the effects of LA heterogeneity and variations in sensitivity and specificity of assays for the detection of antiphospholipid antibodies.     

Study of human papillomavirus infection in patients with anal squamous carcinoma

PURPOSE: The purpose of this study was to determine the incidence of human papillomavirus deoxyribonucleic acid (HPV DNA) in anal squamous carcinoma. METHODS: HPV DNA in situ hybridization for HPV Types 6, 11, 16, 18, 31, 33, and 35 was performed on the formalin-fixed, paraffinembedded tissue from 53 perianal and anal squamous carcinomas and 10 controls. RESULTS: HPV DNA sequences were identified in 18 of 53 anal squamous carcinomas (34 percent). All 10 controls were negative for HPV DNA. Of the 18 positive patients, 10 were perianal squamous carcinomas, and 8 were anal canal squamous carcinomas. Six of the perianal carcinomas were positive for HPV Types 6 and 11. The remaining four perianal carcinomas and all eight of the anal canal carcinomas were positive for HPV Types 16 and 18. CONCLUSION: HPV DNA sequences can be identified in anal squamous carcinomas. Anal squamous epithelium is another site where HPV infection may carry a risk for malignant transformation. One-third of anal squamous carcinomas may be associated with prior HPV infection. Patients with anogenital HPV infection should be routinely screened for anal squamous lesions.     

Drug resistant Haemophilus influenzae from respiratory tract infection in a tertiary care hospital in north India

Haemophilus influenzae is an important respiratory pathogen. Emergence of resistance to various antibiotics is a major problem in patient management. A total of 90 strains of H. influenzae were characterized from specimens obtained from patients of acute respiratory tract infection; 13 (14.4%) belonged to type beta. On biotyping, 90% strains belonged to biotype II. The frequency of resistance to various antibiotics was as follows: cotrimoxazole 33.3% ampicillin 21.1%, cephalexin 7.8%, chloramphenicol 7.8%, ciprofloxacin 2.5% erythromycin and tetracycline 5% each. All the ampicillin-resistant strains produced beta-lactamase as detected by nitrocefin disc method. None of the strains exhibited resistance to cefaclor and third generation cephalosporins. The present study showed emergence of variable resistance to ampicillin, cotrimoxazole and other antibiotics. It is important for the clinical microbiology laboratory to monitor drug resistant strains for instituting appropriate antibiotic therapy of respiratory infections due to H. influenzae.     

Characterization of rat100, a 300-kilodalton ubiquitin-protein ligase induced in germ cells of the rat testis and similar to the Drosophila hyperplastic discs gene

Conjugation of ubiquitin to proteins is activated during spermatogenesis. Ubiquitination is mediated by ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzymes (UBCs or E2s), and ubiquitin protein ligases (E3s). Since we previously showed that the activated ubiquitination is UBC4 dependent, we characterized Rat100, a UBC4-dependent E3 expressed in the testis. Analysis of expressed sequence tag sequences and immunoblotting showed that Rat100 is actually a 300-kDa protein expressed mainly in the brain and testis and is similar to the human E3 identified by differential display (EDD) protein and the Drosophila hyperplastic discs gene, mutants of which cause a defect in spermatogenesis. Rat100 is induced during postnatal development of the rat testis, peaking at d 25. It is localized only in germ cells and is highly expressed in spermatocytes, moderately in round and slightly in elongating spermatids. In contrast to UBC4 whose removal from a testis extract abrogates much of the conjugation activity, immmunodepletion of Rat100 from the extracts had little effect. Rat100 therefore has a limited subset of substrates, some of which appear associated with the E3 as the immunoprecipitate containing Rat100 supported incorporation of (125)I-ubiquitin into high molecular weight proteins. Thus, Rat100 is the homolog of human EDD and likely of Drosophila hyperplastic discs. This homology, together with our results, suggests that induction of this E3 results in ubiquitination of specific substrates, some of which are important in male germ cell development.     

Progestins and cortisol delay while estradiol-17 beta induces early parturition in the guppy, Poecilia reticulata

Fertilization and gestation are intrafollicular in the guppy (Poecilia reticulata), and ovulation occurs at the end of gestation prior to parturition. In this study, the effects in vivo of the ovarian steroids, progesterone, 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17 alpha,20 beta-P), cortisol and estradiol-17 beta, the antiprogestin RU 486, and aromatase inhibitor, 4-hydroxyandrost-4-ene-3,17-dione (4-HAD), on gestation and parturition were studied in the guppy. Progesterone (0.05 and 0.10 micrograms/ml of water), 17 alpha,20 beta-P (0.01 micrograms/ml and greater), cortisol (0.10 micrograms/ml) and 4-HAD (0.10 micrograms/ml) all prolonged gestation presumably by inhibiting ovulation. 17 alpha,20 beta-P was most effective in inhibiting ovulation and parturition for up to 36 days postpartum. This inhibition was reversed when fish were transferred to steroid-free water. Besides extending gestation, 17 alpha,20 beta-P and 4-HAD also inhibited development of vitellogenic oocytes. Estradiol-17 beta (0.05 and 0.10 micrograms/ml) and RU 486 (10 micrograms/g body weight) both induced premature parturition presumably by accelerating onset of ovulation. These results, together with our previous observations on the steroid profile in the guppy, strongly suggest roles for estradiol-17 beta and cortisol in regulating ovulation and parturition.     

Relationship between reduced folate carrier gene polymorphism and non-syndromic cleft lip and palate in Indian population

Objective: Folate metabolism involves absorption, transport, modifications and interconversions of folates. The reduced folate carrier does not participate directly in folate metabolism but plays a major role in intracellular transport of metabolically active 5-methyltetrahydrofolate and maintains the intracellular concentrations of folate. The purpose of this study was to identify the prevalence of reduced folate carrier 1 (RFC1) A80G polymorphism and to further delineate its association with non-syndromic cleft lip and palate (NSCLP) in a south Indian population.

Methods: In the present case-control study, we studied RFC1 gene A80G polymorphism to evaluate its impact on NSCLP risk in south Indian population. Blood samples of 142 cases with NSCLP and 141 controls were collected and genotyped using PCR-RFLP.

Results: The genotype distribution in the control group followed Hardy–Weinberg equilibrium (p?=?0.633). The G allele frequency of cases was 64.8% (184/284) and was significantly lower than that found in the control group 56.4% (160/282). The genotype distributions between NSCLP cases and controls was not significantly different (p?=?0.131). The allelic model significantly increased the risk of NSCLP (G versus A; OR?=?1.40; 95% CI: 1.00–1.97; p?=?0.050). In subgroup analysis, the A80G variant showed significant association for the CLP group in dominant and allelic models.

Conclusions: Altogether, our findings support the hypothesis that RFC1 A80G variant may contribute to NSCLP susceptibility in a south Indian population.