Abnormal intestinal histology in neonates with congenital anomalies of the gastrointestinal tract

In animal models, when swallowing is experimentally prevented in utero, bowel length and weight are reduced, and villus height, crypt depth, and villus function are retarded. Little is known about the intestinal histology in infants with gastrointestinal (GI) tract anomalies. We examined the histological architecture of the intestine in neonates with GI anomalies in comparison to that of normal fetuses. Villus height, area, and length and crypt depth of normal fetuses were quantified in the proximal small bowel (n = 11) and measurements compared to those of surgical specimens of neonates with congenital anomalies of the GI tract (n = 16). Villus height and area and lamina propria height and area increased linearly from 8 to 24 weeks of gestation. In infants with anomalies of the GI tract, the villi were blunted and lacked normal histological architecture, the crypts were disorganized, and the crypt depth was significantly decreased (p = 0.004). Enterocyte height and area were significantly greater in neonates with congenital anomalies of the GI tract. The intestinal histology in neonates with congenital anomalies of the GI tract differs significantly from that of normal fetuses.     

Non-invasive assessment of endothelial function by brachial artery flow mediated vasodilatation and its association with coronary artery disease: an Indian perspective

Endothelial dysfunction is the final common pathway through which various coronary risk factors culminate into atherosclerosis and subsequent coronary artery disease (CAD). Endothelial function can be reliably assessed by flow mediated vasodilatation (FMD) in the brachial artery using high-resolution ultrasonography and has been shown to be an excellent surrogate marker for the presence of CAD. Two hundred and forty-one individuals comprising of 101 patients with CAD (angiographically proven, or with history of documented myocardial infarction) and 140 individuals without CAD were included in the study. All subjects underwent clinical evaluation, fasting lipid profile, treadmill test and FMD assessment. Selected individuals underwent coronary angiography too. Brachial artery diameter and Doppler indices (systolic and diastolic velocity time integrals) were recorded using high resolution ultrasonography at baseline, immediately after and at one minute after release of cuff (occlusion time 5 minutes). FMD was calculated as percentage increase in brachial artery diameter at one minute. FMD index was calculated as the ratio of FMD and percentage increase in flow during reactive hyperaemia. Mean FMD was significantly higher in non-CAD group (8.71+/-4.77%) than in CAD group (3.77+/-2.03%; p < 0.0001). The FMD index was also significantly higher in the non-CAD group (0.031 ) than in CAD group (0.021; p=0.0117). On multiple regression analysis, FMD index was found to be significantly associated with presence of CAD (p=0.0015), independent of conventional cardiovascular risk factors. Endothelial function as assessed by FMD is significantly depressed in patients with established CAD and this association is independent of presence of conventional cardiovascular risk factors.     

Evaluation of standardized versus individualized total parenteral nutrition regime for neonates less than 33 weeks gestation

OBJECTIVE: To evaluate the difference in nutrient intakes and biochemical responses in newborn infants <33 weeks gestation who received standardized versus individualized total parenteral nutrition (TPN) regimes. METHOD: Comparison of nutrient intakes and daily biochemical responses in newborn infants <33 weeks gestation who received standardized regime versus those who received individualized TPN regimes from day 2 to day 7 of life. RESULTS: Twenty-seven infants in the standardized TPN group and 31 infants in the individualized TPN group were compared. There were no statistically significant differences (P > 0.05) between the two groups in gestation, birthweight, Clinical Risk Index for Babies scores, daily TPN volume intake and biochemical responses. Infants in the standardized TPN group received less sodium (P < 0.01) and no potassium on day 2 as required, more protein (P < 0.02) every day, and more calcium and phosphate (P < 0.02 from day 4). CONCLUSION: There were no significant clinical and statistical differences in biochemical responses in newborn infants <33 weeks gestation who received standardized versus individualized TPN regimes during the first week of life. The economic cost of TPN provision using standardized TPN formulation was approximately 30% lower.     

Elective abortion as a primary health service in rural India: experience with manual vacuum aspiration

India allows abortion up to 20 weeks of pregnancy but places restrictions on abortion facilities and providers. Abortion services are especially deficient in rural areas. Although vacuum aspiration is safer, sharp curettage continues to be used by providers as they lack relevant training. This paper describes the provision of first trimester abortion services using manual vacuum aspiration (MVA) in a rural clinic in the state of Rajasthan over a four-year period. Non-use of anaesthesia increased safety and allowed women to return early to a normal routine. Of 534 women, none suffered major complications; 16 required repeat evacuation and the procedure failed in two. We recommend that models based on MVA and including medical methods be piloted in rural areas of a number of states of the country, to establish the feasibility of delivering first trimester abortion as a primary health service. Ways to increase access to second trimester procedures are also required. Current requirements for certification of private facilities are excessive and the process of obtaining certification is arduous. The law in India does not extend these norms to government facilities, which remain under-equipped and lack trained providers. We recommend that certification of facilities be liberalized and applied equally to government and private institutions. There is also a need to rapidly increase training capacity across the country.     

Isolated solitary vertebral body tuberculosis--study of seven cases

AIM: To describe the magnetic resonance imaging (MRI) findings in isolated solitary vertebral body tuberculosis. Also to emphasize tuberculosis as an important entity, besides neoplasms, in the differential diagnosis of pathologies involving a single vertebral body. MATERIAL AND METHODS: The clinical and imaging features of seven patients (four men and three women; age range 18-60 years), with proved solitary vertebral body tuberculosis were retrospectively studied. RESULTS: Isolated solitary vertebral body tuberculosis is seen in only 1.69% of the total proven cases of spine tuberculosis seen in our institute between 1993 and 2002. All patients presented with constitutional symptoms and localized pain and tenderness. MRI showed decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images. Cortical break was seen in three patients of whom epidural and pre-vertebral extensions were seen in one each. CONCLUSIONS: Although tuberculosis affecting a solitary vertebral body is rare it should be considered as an important differential diagnosis, besides neoplasms. In these cases MRI serves as the best imaging technique available for diagnosis. However, confirmation can only be made on histopathology or culture of the specimen.     

Role of RLIP76 in lung cancer doxorubicin resistance: I. The ATPase activity of RLIP76 correlates with doxorubicin and 4-hydroxynonenal resistance in lung cancer cells

RLIP76 functions as an ATP-dependent transporter of amphiphilic chemotherapeutic drugs such as doxorubicin (DOX, adriamycin), as well as of glutathione-conjugates of endogenous electrophilic toxins such as 4-hydroxynonenal (4HNE). RLIP76 couples transport and ATP-hydrolysis with a 1:1 stoichiometry, making the ATPase activity of RLIP76 an excellent surrogate for its transport activity. Present studies were performed to determine the relationship of the RLIP76 ATPase activity with DOX and 4HNE resistance in a panel of 13 native human lung cancer cell lines. RLIP76 was purified from each cell line and homogeneity demonstrated by SDS-PAGE and amino acid composition analysis. Anti-RLIP76 antibodies were shown by Ouchterlony double immunodiffusion tests to be non-cross-reactive with any other proteins including P-glycoprotein (Pgp) or multidrug resistance associated protein (MRP). These antibodies completely immunoprecipitated ATPase activity of purified RLIP76 fractions, further confirming homogeneity of purified RLIP76. RLIP76 ATPase purified from NSCLC cell lines was about 2-fold more active than that from SCLC in the absence of the stimulator dinitrophenyl S-glutathione (206+/-47, n=7 vs. 94+/-22, n=6, nmol/min/mg protein, respectively), or in its presence (340+/-60, n=7 vs. 186+/-32, n=6, nmol/min/mg; p<0.01). Partial tryptic digest revealed a 44 kDa internal fragment of RLIP76 beginning at Thr-294 in NSCLC cell lines. This fragment was absent from all SCLC, suggesting the possibility that the activity of RLIP76 in SCLC and NSCLC is differentially regulated through post-translational modifications. Taken together, these findings suggest that RLIP76 activity is a general determinant of 4HNE and DOX resistance, and that its activity contributes to the drug-resistant phenotype of NSCLC.     

Role of RLIP76 in lung cancer doxorubicin resistance: III. Anti-RLIP76 antibodies trigger apoptosis in lung cancer cells and synergistically increase doxorubicin cytotoxicity

RLIP76 (ral-binding protein, RalBP1) is a non-ABC multi-specific transporter of amphiphilic chemotherapeutic drugs such as doxorubicin (DOX) and glutathione-electrophile conjugates. In the present studies, we used polyclonal rabbit anti-human RLIP76 IgG to inhibit RLIP76 function for determining the role of RLIP76 in DOX resistance of NSCLC cells. Western blot analyses and immunohistochemistry studies showed no recognition of other protein in crude NSCLC cell homogenates by anti-RLIP76, confirming the specificity of anti-RLIP76 IgG. In immunohistochemistry and flow cytometry studies, these antibodies recognized RLIP76 domain(s) on the cell surface. Cells coated with anti-RLIP76 IgG accumulated significantly greater DOX than cells coated with pre-immune IgG. Synergy was calculated using the Chou-Talalay median effect analysis. Herceptin was the positive control, and pre-immune IgG and Rituxan (anti-CD20) were negative controls. The interaction of anti-RLIP76 IgG and DOX were markedly synergistic (CI 0.36+/-0.27). Lesser synergy was observed between Herceptin and DOX (CI 0.75+/-0.49). Interaction between Herceptin and anti-RLIP76 was only additive (CI 1.12+/-0.5). Human IgG, Rituxan, and rabbit pre-immune IgG controls had no effect on DOX toxicity. DNA-laddering confirmed that DOX triggered apoptosis. Anti-RLIP76 IgG alone as well as Herceptin alone also triggered apoptosis in all 6 NSCLC cell lines. Anti-RLIP76 IgG and Herceptin were shown to increase DOX accumulation in NSCLC. These results demonstrated that specific inhibition of the transport function of RLIP by anti-RLIP76 IgG can trigger apoptosis and synergistically increase DOX cytotoxicity in NSCLC.     

Primary carcinoma of fallopian tube--a case study

Primary carcinoma of fallopian tube is a rare entity. We report an interesting case of primary carcinoma of fallopian tube with contralateral lymph node involvement. The clinicopathological findings and its management is presented.