Comparison of rapid colorimetric method with conventional method in the isolation of Mycobacterium tuberculosis

The aim of the study was to evaluate two methods (colorimetric and conventional) for isolation of Mycobacterium tuberculosis. A total of 500 clinical specimens were processed by modified Petroff's method and then inoculated into MB/BacT-240 system bottles and on LJ medium slopes. The specimens included 242 sputum, 95 gastric aspirates, 47 pleural fluids, 45 CSF, 32 urine, 18 pus, 11 bronchoalveolar lavage, 3 tissue, 2 stool, 2 lymphnode specimens, 2 synovial fluid and 1 bronchial wash specimens. The isolation rate was 16.4% by the colorimetric method and 2.2% by the conventional method. The mean detection time was 16 days and 26 days respectively. Among 36 direct smear positive samples, 63.9%(23/36) and 30%(11/36) were positive by colorimetric and conventional methods respectively. Out of 464 direct smear negative samples 12.9%(60/464) and 0.6%(3/464) were positive by colorimetric and conventional methods respectively. Therefore, colorimetric method enables rapid detection leading to early diagnosis and drug susceptibility testing.     

Rational Use of Protein Supplements in the Elderly—Relevance of Gastrointestinal Mechanisms

Protein supplements are increasingly used by older people to maintain nutrition and prevent or treat loss of muscle function. Daily protein requirements in older people are in the range of 1.2 gm/kg/day or higher. Many older adults do not consume this much protein and are likely to benefit from higher consumption. Protein supplements are probably best taken twice daily, if possible soon after exercise, in doses that achieve protein intakes of 30 gm or more per episode. It is probably not important to give these supplements between meals, as we have shown no suppressive effects of 30 gm whey drinks, and little if any suppression of 70 gm given to older subjects at varying time intervals from meals. Many gastrointestinal mechanisms controlling food intake change with age, but their contributions to changes in responses to protein are not yet well understood. There may be benefits in giving the supplement with rather than between meals, to achieve protein intakes above the effective anabolic threshold with lower supplement doses, and have favourable effects on food-induced blood glucose increases in older people with, or at risk of developing, type 2 diabetes mellitus; combined protein and glucose drinks lower blood glucose compared with glucose alone in older people.     

ATM mutations in patients with hereditary pancreatic cancer

Pancreatic cancers are the fourth most-common cause of cancer-related deaths in the Western world, with >200,000 cases reported in 2010. Although up to 10% of these cases occur in familial patterns, the hereditary basis for predisposition in the vast majority of affected families is unknown. We used next-generation sequencing, including whole-genome and whole-exome analyses, and identified heterozygous, constitutional, ataxia telangiectasia mutated (ATM) gene mutations in 2 kindreds with familial pancreatic cancer. Mutations segregated with disease in both kindreds and tumor analysis demonstrated LOH of the wild-type allele. By using sequence analysis of an additional 166 familial pancreatic cancer probands, we identified 4 additional patients with deleterious mutations in the ATM gene, whereas we identified no deleterious mutations in 190 spouse controls (P = 0.046). When we considered only the mostly severely affected families with 3 or more pancreatic cancer cases, 4 deleterious mutations were found in 87 families (P = 0.009). Our results indicate that inherited ATM mutations play an important role in familial pancreatic cancer predisposition. SIGNIFICANCE: The genes responsible for the majority of cases of familial pancreatic ductal adenocarcinoma are unknown. We here identify ATM as a predisposition gene for pancreatic ductal adenocarcinoma. Our results have important implications for the management of patients in affected families and illustrate the power of genome-wide sequencing to identify the basis of familial cancer syndromes.     

Familial clustering of non-nuclear autoantibodies and C3 and C4 complement components in systemic lupus erythematosus

OBJECTIVE: To determine whether key features of systemic lupus erythematosus (SLE), namely, production of non-nuclear antibodies (anti-C1q and anticardiolipin antibodies [aCL]) and depletion of complement components C3 and C4, aggregate in families. In addition, we examined relationships between anti-C1q and C3 and C4 levels. METHODS: The study cohort comprised 1,037 predominantly white (82%) nuclear families in which at least 1 member had SLE. Associations of antibody measurements between probands and their unaffected siblings were examined using parametric and nonparametric analyses, along with associations between unaffected siblings and their parents. The heritability of anti-C1q, C3, and C4 was estimated, and interdependencies between these factors were examined in a regression model accounting for the family structure of the data set. RESULTS: We demonstrated associations between siblings for anti-C1q (odds ratio [OR] 3.74, 95% confidence interval [95% CI] 2.65, 5.28) and IgG and IgM aCL (OR 4.08, 95% CI 1.83, 5.13 and OR 2.06, 95% CI 1.46, 2.91, respectively) and, for anti-C1q, association between unaffected parents and their unaffected offspring (OR 4.34, 95% CI 2.16, 8.72). We also demonstrated significant heritability of anti-C1q, C3, and C4 (approximately 45%). Anti-C1q was negatively associated with C3 and C4 in SLE probands but not in their healthy relatives. CONCLUSION: Non-nuclear antibodies and C3 and C4 cluster within the families of SLE probands, suggesting that specific autoantibody formation is partly genetically determined, even if the total genetic effect in unaffected relatives is insufficient to cause disease. Anti-C1q antibodies accelerate C3 and C4 depletion in patients with SLE but have no effect in the absence of disease.     

Correlation of polyp number and family history of colon cancer with germline MYH mutations.

BACKGROUND & AIMS: Affected individuals with biallelic MYH mutations are believed to display multiple adenomatous polyps without evidence of vertical transmission. Our goal was to determine the detection rate of germline MYH mutations in a high-risk gastrointestinal cancer clinic population by using polyp number as a selection criterion. METHODS: Patients were screened for the 2 most common MYH mutations: Y165C and G382D. The complete MYH coding region was sequenced in cases with a heterozygous mutation. RESULTS: Among 45 patients with more than 15 adenomatous polyps not diagnosed with familial adenomatous polyposis, 7 (15.6%) had biallelic MYH mutations. When 122 participants from a high-risk gastrointestinal cancer clinic who did not fulfill these criteria were tested, 2 additional patients with biallelic mutations were identified. Both had young-onset colorectal cancer (age, <50 y) with fewer than 15 polyps. Surprisingly, most of the 9 patients with biallelic MYH mutations reported family histories consistent with the hereditary nonpolyposis colorectal cancer syndrome (HNPCC), with 7 cases meeting at least 1 of the Bethesda criteria, 5 cases fulfilling 3 Bethesda criteria, and 2 cases fulfilling the Amsterdam II criteria. CONCLUSIONS: Most individuals with MYH mutations exhibit multiple adenomatous polyps. However, 22% of cases were missed when this was the sole criterion for germline testing. A significant number reported a strong family history of cancer that was consistent with HNPCC. MYH testing thus can be considered for patients who meet clinical criteria for HNPCC in the absence of DNA mismatch repair gene mutations.     

Determinants of colorectal cancer screening in women undergoing mammography

OBJECTIVES: Women who participate in screening for breast cancer are more likely to participate in screening for colorectal cancer. We studied such a motivated group of women to identify predictors of, and barriers to, participation in colorectal cancer screening by endoscopy. METHODS: We distributed surveys to 551 women > or = 50 yr of age while they were awaiting mammography at four sites in and around Boston, MA from June to September, 2000. The 40-question survey assessed knowledge, attitudes, and beliefs about, and behaviors toward, breast and colorectal cancer screening. Regression models were used to determine factors associated with having had sigmoidoscopy or colonoscopy. RESULTS: Seventy-nine percent of the women completed all or part of the survey. Half (221/438) reported ever having had sigmoidoscopy or colonoscopy. Of these, 93% did so at the recommendation of their primary care provider. Factors associated with participation in endoscopic screening included compliance with annual fecal occult blood testing, a family history of colorectal cancer, and indifference toward the gender of the doctor performing the endoscopy. CONCLUSIONS: Women undergoing mammography overwhelmingly cite the recommendation of their primary care provider as the reason for participating in colorectal cancer screening by endoscopy. Women who preferred a female endoscopist were less likely to have been screened. Whenever possible, primary care providers should offer women the choice of a female endoscopist for colorectal cancer screening.