Vitamin D receptor <Emphasis Type="Italic">Fok</Emphasis>I and <Emphasis Type="Italic">Bsm</Emphasis>I gene polymorphism and its association with grade and stage of renal cell carcinoma in North Indian population

Vitamin D exerts its activity through binding to the high-affinity nuclear vitamin D receptor (VDR), and majority of genetic studies have primarily focused on variation within this gene. Therefore, analysis of genetic variation in VDR genes may provide insight into the role of vitamin D in renal cell carcinoma (RCC) etiology in our study population. This study investigated whether VDR gene polymorphisms were associated with increased risk and prognosis of RCC in the North Indian population. Genotyping of two polymorphic sites (FokI and BsmI) in the VDR gene of 196 RCC cases and 250 healthy controls was performed via PCR-RFLP. The frequency of homozygous genotype FF was 31.6%, heterozygous Ff was 48.0%, and homozygous ff was 20.4% in cases, whereas in controls it was 45.6%, 39.2%, and 15.2%, respectively; thus, there was a significant difference between the two groups (p ^Trend = 0.011) in the univariate model. The frequencies of the BB, Bb, and bb genotypes were 25.5%, 44.9% and 29.6% in cases, respectively, while in controls it was 33.2%, 52.0% and 14.8%, respectively; thus, there was a significant difference between the two groups (p ^Trend = 0.001) in the univariate model. The two high-risk genotype ff of FokI and bb of BsmI of VDR showed a cumulative 1.87-fold increase in risk to RCC. Moreover, the FF genotype was associated with lower pathological stage and histological grade. Our results suggest that the FokI and BsmI genotypes of VDR gene may be implicated in the pathogenesis of RCC.     

Toll-like receptor 4 polymorphisms in dengue virus-infected children

Differential viral recognition by cells bearing Toll-like receptor 4 (TLR4) polymorphisms Asp299Gly and Thr399Ile may influence susceptibility and severity of dengue virus infection. In central Java, Indonesia, we investigated 201 children with dengue hemorrhagic fever (DHF) and 179 healthy controls. Patients and controls were mostly ethnic Javanese. A nearly complete cosegregation of the two mutations was observed. The TLR4 299/399 genotype was found in five patients and four controls. Prevalence of the TLR4 299/399 genotype did not differ significantly between controls and DHF patients or between patients with different severities of DHF. Also, vascular leakage in patients with different TLR4 genotypes did not differ. Thus, the 299/399 TLR4 haplotype has only minor influence on susceptibility and severity of complicated dengue virus infection.     

Role of discrimination indices in differentiation of beta thalassaemia trait and iron deficiency anaemia

Iron deficiency anaemia (IDA) and beta thalassaemia trait (BTT) are the most common causes of microcytic hypochromic anaemias. Several discrimination indices have been introduced to discriminate quickly these similar entities via parameters obtained from automated cell counter. The purpose of the study was to evaluate the value of five discrimination indices in differentiation of BTT and IDA. This study consists of 57 cases of BTT and 72 cases of IDA. Five discrimination indices evaluated in this study for differentiation of BTT and IDA were red blood cell (RBC) count, red blood cell distribution width index (RDWI), Green & King Index (G & K), Mentzer index (MI) and England & Fraser (E & F) index. Sensitivity, specificity, positive and negative predictive values and Youden's index (YI) had been calculated. RBC count and RDWI appears to be reliable and useful index for the differentiation of BTT and IDA, as both of the indices had more than 80% sensitivity, specificity in differentiation of IDA and BTT. Patients with microcytic hypochromic anaemia could be easily screened out for BTT and IDA through these discrimination indices in the absence of other complicated diseases.     

Synthesis, characterization, antibacterial, antifungal, and immunomodulating activities of gatifloxacin derivatives

Gatifloxacin is a synthetic broad-spectrum fluorquinolone antibacterial agent with a 3-methylpiperazinyl-side chain at position 7 and a methoxy group at position 8 of the quinolone ring. In the present study different analogues of gatifloxacin were prepared; the piperazinyl ring was chosen as the center of reaction for synthesizing this series of derivatives. The structures of these derivatives were established using spectroscopic techniques such as IR, ¹H NMR, and EIMS. In vitro antibacterial and antifungal activities were evaluated by disc diffusion method and these derivatives were compared with in-use fluoroquinolones like gatifloxacin, sparfloxacin, and gemifloxacin. Derivative A proved very potent against Gram-negative organisms, especially Pseudomonas aeruginosa, Shigella flexeneri, and Klebseilla pneumoniae, and derivatives A–C exhibited good antifungal activity compared to in-use quinolones. In addition, gatifloxacin and derivatives were investigated for immunomodulating activities. Derivative B has good anti-inflammatory activity, with IC₅₀ < 12.5 μg/ml.     

Antineutrophil cytoplasmic antibodies in Wegener's granulomatosis

The prevalence of antineutrophil cytoplasmic antibodies (ANCA) was studied in 12 children with Wegener's granulomatosis. The serum samples were taken in the active phase of disease and were screened for ANCA by indirect immunofluorescence with normal neutrophils and enzyme linked immunosorbent assay (ELISA) using crude neutrophil extract, proteinase 3, myeloperoxidase, cathepsin G, lactoferrin, and elastase as antigens. Of these 12 patients, 10 wre positive for ANCA in the active phase of their illness, and they showed a predominantly cytoplasmic ANCA staining pattern on indirect immunofluorescence. There were high titres of ANCA directed against crude neutrophil extract, proteinase 3, myeloperoxidase, and cathepsin G. IgM isotypes occurred as commonly as IgG isotypes. Therefore, screening for ANCA is usually but not invariably positive in children with Wegener's granulomatosis. Specific diagnosis still relies on clinical and pathological features, and the value of ANCA in the diagnosis of paediatric Wegener's granulomatosis requires further study.     

Continuous extradural infusion of ropivacaine for prevention of postoperative pain after major orthopaedic surgery

We studied 151 patients undergoing total hip or knee arthroplasty, or cruciate ligament reconstruction in a multicentre study in Australia and New Zealand. Patients were openly allocated randomly to one of five treatment groups or to a control group. General anaesthesia was induced after introduction of extradural block with 0.5% ropivacaine. After surgery, patients received an extradural infusion of 0.2% ropivacaine at 6, 8, 10, 12 or 14 ml h-1 or received no postoperative extradural infusion (control group). All patients had access to i.v. PCA morphine for supplementary analgesia. Morphine consumption was lower in all treatment groups compared with the control group, decreasing with increasing ropivacaine infusion rate. Median VAS scores were lower in all ropivacaine infusion groups compared with the control group for the first 10 h of the study; however by the end of the study, VAS scores were similar in all groups. The higher ropivacaine infusion rates caused a slower convergence of spread of the initial sensory block and a higher degree of motor block. The overall incidence of side effects was similar, with the exception of a higher incidence of urinary retention and hypotension in the groups receiving the higher rates of ropivacaine. The quality of treatment scores were similar for all treatment groups.      

Iron deficiency in lead poisoning

The anemia of lead poisoning is multifactorial. Of 44 hematologically evaluated children with class III or IV lead intoxication, 50 per cent were anemic and 39 per cent were iron deficient. Iron deficiency may play an important role in the anemia of lead poisoning. Early diagnosis and correction of nutritional deficiencies may decrease the metabolic toxicity of lead poisoning.