Descriptive epidemiology of lymphoid and haemopoietic malignancies in Bangalore,India

Lymphoid and haemopoietic malignancies as a group constitute one of the important cancers in India, as elsewhere in the world. While information on incidence and mortality of these cancers, and that on survival, are available from most developed countries, there are very few reports describing this experience in developing ones. Population-based cancer registration commenced in Bangalore, India, in January 1982, under the auspices of the Indian Council of Medical Research. This source provides fairly complete and reliable incidence data, but, in order to obtain mortality and survival information, active follow-up involving visits of homes of patients was undertaken. Between 1982 and 1989, 1397 cases of lymphoid and haemopoietic malignancies were registered in the Bangalore cancer registry, giving an age-adjusted incidence rate of 7.7 and 4.8 per 100,000 in males and females respectively. Active follow-up provided mortality/survival information in 1267 or 90.7% of these cases. The overall observed 5-year survival for these cancers combined (both sexes) was 26%, and relative survival 28.4%. The 5-year survival rate was lower in all the individual lymphomas and leukaemias as compared with similar reports from the developed countries. Survival in Hodgkin's disease was influenced by clinical stage and age at presentation.     

Molecular typing of selected Enterococcus faecalis isolates: pilot study using multilocus sequence typing and pulsed-field gel electrophoresis

The present study compared the recently developed multilocus sequence typing (MLST) approach with a well-established molecular typing technique, pulsed-field gel electrophoresis (PFGE), for subspecies differentiation of Enterococcus faecalis isolates. We sequenced intragenic regions of three E. faecalis antigen-encoding genes (ace, encoding a collagen and laminin adhesin; efaA, encoding an endocarditis antigen; and salA, encoding a cell wall associated antigen) and one housekeeping gene (pyrC) of 22 E. faecalis isolates chosen largely for their temporal and geographical diversity, but also including some outbreak isolates. MLST analysis of polymorphic regions of these four genes identified 13 distinct sequence types (STs) with different allelic profiles; the composite sequences generated from the four sequenced gene fragments of individual isolates showed 98.3 to 100% identity among the 22 isolates. We also found that the allelic profiles from two sequences, ace and salA, were sufficient to distinguish all 13 STs of this study. The 13 STs corresponded to 12 different PFGE types, with one previously designated PFGE clone (a widespread U.S. clone of beta-lactamase-producing isolates) being classified into two highly related STs which differed at 2 of 2,894 bases, both in the same allele. MLST also confirmed the clonal relationships among the isolates of two other PFGE clonal groups, including vancomycin resistant isolates. Thus, this pilot study with representative E. faecalis isolates suggests that, similar to PFGE, the sequence-based typing method may be useful for differentiating isolates of E. faecalis to the subspecies level in addition to identifying outbreak isolates.     

Studies on glutamic-oxalacetic (GOT) and glutamic-pyruvic (GPT) transaminases of swine kidney worm Stephanurus dentatus (Diesing, 1839)

Summary Biochemical studies on the two transaminases GOT and GPT of swine kidney worm Stephanurus dentatus have been made. GOT has been found much more active than GPT. Enzyme activities are based on the formation of oxaloacetate (GOT) or pyruvate (GPT) from aspartic acid and alanine respectively with oxoglutarate. A linear relationship is observed between the enzyme concentration and activity. GOT shows a maximum activity at pH 8.0 and Michaelis constant 9×10^–3 M for male and 2.9×10^–3 M for female. GPT has an optimum pH of 7.5 and a Michaelis constant 19×10^–3 M for male and 8×10^–3 M for female. The optimum temperature for both GOT and GPT was 60° C.     

31P and 1H MRS of DB‐1 melanoma xenografts: lonidamine selectively decreases tumor intracellular pH and energy status and sensitizes tumors to melphalan

In vivo ³¹P MRS demonstrates that human melanoma xenografts in immunosuppressed mice treated with lonidamine (LND, 100 mg/kg intraperitoneally) exhibit a decrease in intracellular pH (pH_i) from 6.90 ± 0.05 to 6.33 ± 0.10 (p < 0.001), a slight decrease in extracellular pH (pH_e) from 7.00 ± 0.04 to 6.80 ± 0.07 (p > 0.05) and a monotonic decline in bioenergetics (nucleoside triphosphate/inorganic phosphate) of 66.8 ± 5.7% (p < 0.001) relative to the baseline level. Both bioenergetics and pH_i decreases were sustained for at least 3 h following LND treatment. Liver exhibited a transient intracellular acidification by 0.2 ± 0.1 pH units (p > 0.05) at 20 min post‐LND, with no significant change in pH_e and a small transient decrease in bioenergetics (32.9 ± 10.6%, p > 0.05) at 40 min post‐LND. No changes in pH_i or adenosine triphosphate/inorganic phosphate were detected in the brain (pH_i, bioenergetics; p > 0.1) or skeletal muscle (pH_i, pH_e, bioenergetics; p > 0.1) for at least 120 min post‐LND. Steady‐state tumor lactate monitored by ¹H MRS with a selective multiquantum pulse sequence with Hadamard localization increased approximately three‐fold (p = 0.009). Treatment with LND increased the systemic melanoma response to melphalan (LPAM; 7.5 mg/kg intravenously), producing a growth delay of 19.9 ± 2.0 days (tumor doubling time, 6.15 ± 0.31 days; log₁₀ cell kill, 0.975 ± 0.110; cell kill, 89.4 ± 2.2%) compared with LND alone of 1.1 ± 0.1 days and LPAM alone of 4.0 ± 0.0 days. The study demonstrates that the effects of LND on tumor pH_i and bioenergetics may sensitize melanoma to pH‐dependent therapeutics, such as chemotherapy with alkylating agents or hyperthermia. Copyright © 2012 John Wiley & Sons, Ltd.     

Expressions of Iba1 and galectin-3 (Gal-3) in thioacetamide (TAA)-induced acute rat liver lesions

Ionized calcium binding adaptor molecule 1 (Iba1) is associated with membrane ruffling and motility of cells. Galectin-3 (Gal-3) is a β-galactoside binding animal lectin, and regulates fibrogenesis probably through transforming growth factor-β1. To evaluate macrophage properties, expressions of Iba1 and Gal-3 were investigated, in relation to macrophages expressing CD68 (ED1; reflecting increased phagocytosis) and CD163 (ED2; implying proinflammatory factor productions) in centrilobular lesions induced in rat livers with thioacetamide (TAA; 300 mg/kg body weight, once intraperitoneally). In agreement with expression patterns of CD68⁺ and CD163⁺ macrophages, cells reacting to Iba1 and Gal-3 were increased in numbers on post-injection (PI) days 1–5, peaking on day 2; thereafter, the positive cells gradually decreased to control levels until PI days 7 and 10. The increased expressions of Iba1 and Gal-3 were confirmed at mRNA levels by the RT-PCR. Double immunofluorescence staining on PI days 2 and 3 demonstrated Iba1 expression in 15–46% of CD68⁺ and CD163⁺ macrophages, and Gal-3 expression in 65–82% of CD68⁺ and CD163⁺ macrophages; Gal-3 expression was observed in 84–93% of Iba1⁺ cells. Interestingly, Gal-3 was also expressed in a small number of α-smooth muscle actin-positive myofibroblasts in fibrotic lesions developed in injured centrilobular areas. These findings indicate that macrophages with various functions can participate in development of liver lesions and resultant fibrosis. Besides CD68 and CD163, Iba1 and Gal-3 immunohistochemistry for macrophages would be useful to analyze the pathogenesis behind developing hepatotoxicity.     

Epidemiology of Chronic Kidney Disease,With Special Emphasis on Chronic Kidney Disease of Uncertain Etiology,in the North Central Region of Sri Lanka

Background

The aim of the study was to identify the epidemiology of chronic kidney disease of uncertain etiology in Sri Lanka.

Methods

A cross-sectional study was carried out by analyzing health statistics, and three cohort studies were conducted (n = 15 630, 3996, and 2809) to analyze the demographic information, age-specific prevalence, etiology, and stage of presentation. We screened 7604 individuals for chronic kidney disease of uncertain etiology.

Results

The results showed that the male:female ratio was 2.4:1, the mean age of patients was 54.7 ± 8 years, 92% of the patients were farmers, and 93% consumed water from shallow dug wells. Familial occurrence was common (36%). The prevalence of chronic kidney disease in different age groups was 3% in those aged 30–40 years; 7% in those aged 41–50 years, 20% in those aged 51–60 years, and 29% in those older than 60 years. Chronic kidney disease of uncertain etiology was diagnosed in 70.2% of patients, while 15.7% and 9.6% were due to hypertension and diabetic mellitus, respectively. The majority of patients were stage 4 (40%) at first presentation, while 31.8% were stage 3 and 24.5% were stage 5. Stage 1 and 2 presentation accounted for only 3.4%.

Conclusions

Low prevalence of CKDU was noticed (1.5%) among those who consumed water from natural springs. Prevalence was highest among males, rice farming communities, and those presenting at later disease stages.Key words: chronic kidney disease, uncertain etiology, epidemiology, North Central Province, male farmers, natural spring water