Nasofacial conidiobolomycosis.

A case of Nasofacial Zygomycosis in a 15-year-old male patient from South India is reported. This patient had typical thickening of the nasofacial mucosa and the skin overlying it. The diagnosis was confirmed with fungal cultures. Although initially good response to treatment with potassium iodide was achieved, later the response was unsatisfactory, probably partly due to irregularity in treatment. Treatment with sulphamethoxazole--trimethoprim and prednisolone combination has resulted in remarkable improvement.     

Carrier analysis and prenatal diagnosis of haemophilia A in North India

The feasibility of DNA diagnosis for haemophilia A in North India was evaluated using intragenic polymorphic DNA markers in factor VIII gene for linkage analysis as well as direct detection of inversion mutation in intron 22 of the gene. The informativity of RFLP (HindIII, BclI and XbaI) and STR (introns 13 and 22) markers for linkage analysis in factor VIII gene was determined in 100 normal individuals. The observed heterozygosity for RFLP markers HindIII, BclI and XbaI was 0.63, 0.60 and 0.48 while that of STR markers introns 13 and 22 were 0.60 and 0.40 respectively. Six and four alleles were identified for introns 13 and 22 and the most frequent allele was 13(CA)26 and 22(AG)n(GT)26 with an allele frequency of 0.53 and 0.62 respectively. The heterozygosities observed for RFLP markers was higher (>70%) than the STR markers (50%) in the affected families with haemophilia A. Inversion mutation was detected in 37% of severely affected patients. Based on present and previous studies from India, a strategy has been proposed to provide molecular diagnosis to a large number of undiagnosed cases of haemophilia A.     

Solar disinfection of water for diarrhoeal prevention in southern India.

AIMS: To evaluate the efficacy and acceptability of solar irradiation in the prevention of diarrhoeal morbidity in children under 5 years of age, in an urban slum in Vellore, Tamil Nadu. METHODS: A total of 100 children were assigned to receive drinking water that had been subjected to solar disinfection in polyethylene terephthalate bottles. One hundred age and sex matched controls were also selected. Both groups were followed by weekly home visits for a period of six months for any diarrhoeal morbidity. At the end of the follow up period, the acceptability of the intervention was assessed by interviews, questionnaires, and focus group discussions. RESULTS: There was significant reduction in the incidence, duration, and severity of diarrhoea in children receiving solar disinfected water, despite 86% of the children drinking water other than that treated by the intervention. The incidence of diarrhoea in the intervention group was 1.7 per child-year, and among controls 2.7 per child-year, with an incidence rate ratio of 0.64 (95% CI -0.48 to 0.86). The risk of diarrhoea was reduced by 40% by using solar disinfection. In qualitative evaluation of acceptability, most women felt that solar disinfection was a feasible and sustainable method of disinfecting water. CONCLUSIONS: Solar disinfection of water is an inexpensive, effective, and acceptable method of increasing water safety in a resource limited environment, and can significantly decrease diarrhoeal morbidity in children.     

Overall accuracy of the BpTRU--an automated electronic blood pressure device

BACKGROUND: The objective of this report is to combine the data from an earlier adult study with the data from a paediatric study in order to determine the overall accuracy of the BpTRU (BPM-100 model) as compared to the recognized standard, auscultatory mercury sphygmomanometer. DESIGN: The individual blood pressure points recorded for both adult and paediatric studies were compared directly to its corresponding observer reference measurements from data collected and stored from the two separate studies. There were 255 sets of readings in the adult study and 162 sets from the paediatric study, which were combined to make 417 pairs of blood pressure readings for this study. METHODS: The overall observer standard reference mean for the 417 measurements was calculated and the difference between this and the overall mean BPM-100 was calculated with SD and ranges. Measurements within 5, 10 and 15 mmHg agreement were expressed as percentages. RESULTS: A total of 121 subjects were included for this study (85 from the adult study and 36 from the paediatric study). From these, 417 paired measurements were recorded. The mean difference between the BpTRU and the reference standard systolic blood pressure (BP) was 0.47+/-5.40 mmHg with 89.2% measurements within 5 mmHg, 96.4% within 10 mmHg and 99.3% within 15 mmHg. The mean difference between the BpTRU and reference diastolic BP was -2.12+/-5.93 mmHg with 81.1% within 5 mmHg, 92.1% within 10 mmHg and 97.6% within 15 mmHg. CONCLUSION: The BpTRU has been shown to be an accurate non-invasive blood pressure monitoring device in the general population over a wide range of ages (3-83 years). This combined study meets all requirements of the Association of Advancement of Medical Instrumentation and achieved a grade 'A' in the BHS protocol.     

Generalized Multifactor Dimensionality Reduction (GMDR) Analysis of Drug-Metabolizing Enzyme-Encoding Gene Polymorphisms may Predict Treatment Outcomes in Indian Breast Cancer Patients

Background

Prediction of response and toxicity of chemotherapy can help personalize the treatment and choose effective yet non-toxic treatment regimen for a breast cancer patient. Interplay of variations in various drug-metabolizing enzyme (DME)-encoding genes results in variable response and toxicity of chemotherapeutic drugs. Generalized multi-analytical (GMDR) approach was used to determine the influence of the combination of variants of genes encoding phase 0 (SLC22A16); phase I (CYP450, NQO1); phase II (GSTs, MTHFR, UGT2B15); and phase III (ABCB1) DMEs along with confounding factors on the response and toxicity of chemotherapeutic drugs in breast cancer patients.

Methods

In an Indian breast cancer patient cohort (n = 234), response to neo-adjuvant chemotherapy (n = 111) and grade 2–4 toxicity to chemotherapy were recorded. Patients were genotyped for 19 polymorphisms selected in four phases of DMEs by PCR or PCR–RFLP or Taqman allelic discrimination assay. Binary logistic regression and GMDR analysis was performed. Bonferroni test for multiple comparisons was applied, and p value was considered to be significant at <0.025.

Results

For ABCB1 1236C>T polymorphism, CT genotype was found to be significantly associated with response to NACT in uni-variate and multi-variate analysis (p = 0.018; p = 0.013). The TT genotype of NQO1 609C>T had a significant association with (absence of) grade 2–4 toxicity in uni-variate analysis (p = 0.021), but a non-significant correlation in multi-variate analysis. In GMDR analysis, interaction of CYP3A5*3, NQO1 609C>T, and ABCB1 1236C>T polymorphisms yielded the highest testing accuracy for response to NACT (CVT = 0.62). However, for grade 2–4 toxicity, CYP2C19*2 and ABCB1 3435C>T polymorphisms yielded the best interaction model (CVT = 0.57).

Conclusion

This pharmacogenetic study suggests a role of higher order gene–gene interaction of DME-encoding genes, along with confounding factors, in determination of treatment outcomes and toxicity in breast cancer patients. This can be used as a potential objective tool for individualizing breast cancer chemotherapy with high efficacy and low toxicity.

     

Association of Toll-like receptor-4 (Asp299Gly and Thr399Ileu) gene polymorphisms with gastritis and precancerous lesions

A Toll-like receptor-4 (TLR-4) Asp299Gly and Thr399Ileu substitution reduces responsiveness to Helicobacter pylori (H. pylori) lipopolysaccharide. CagA+ strains of H. pylori are known to be associated with gastroduodenal diseases. Therefore we aimed to evaluate association of TLR-4 substitutions and CagA seropositivity with gastritis and precancerous lesions in a northern Indian population. After upper gastrointestinal endoscopy, 130 rapid urease test (RUT)-positive patients with nonulcer dyspepsia (NUD) were included. Patients with NUD were also screened for H. pylori infection using modified Giemsa staining and anti-CagA IgG enzyme-linked immunoabsorbent assay. All patients and 200 asymptomatic control subjects were genotyped for TLR-4 substitutions using polymerase chain reaction-restriction fragment length polymorphism. We observed that frequencies of TLR-4 Asp299Gly variants were comparable between patients and control subjects, and also between positive and negative groups of precancerous lesions in patients. Frequencies of TLR-4 399Ileu allele (8% vs 3%, p = 0.008) and Asp299-Ileu399 haplotype (6.5% vs 3%, p = 0.022) were higher in patients than in control subjects at risk for gastritis (OR = 2.6 and 2.5, respectively). TLR-4 399Ileu allele carriers had higher risk for plasma cell infiltration (p = 0.023, OR = 10.6) that led to atrophy (p = 0.028, OR = 4.2) and intestinal metaplasia (p = 0.009, OR = 4.7). CagA positivity was more frequently associated with lymphoid follicle formation (p = 0.033, OR = 2.53). In conclusion TLR-4 Thr399Ileu substitution may be a risk factor for gastritis and precancerous lesions. CagA positivity may be a risk factor for lymphoid follicle development but not for other precancerous lesions in a northern Indian population.