Ursodeoxycholic acid and F(6)-D(3) inhibit aberrant crypt proliferation in the rat azoxymethane model of colon cancer: roles of cyclin D1 and E-cadherin.

We have previously demonstrated that ursodeoxycholic acid(UDCA) and a fluorinated analogue of vitamin D(3), F(6)-D(3),inhibited colonic carcinogenesis in the azoxymethane (AOM) model. Generalized colonic mucosal hyperproliferation and aberrant crypt foci (ACF) are intermediate biomarkers of colon cancer. Using these biomarkers, in this study we examined the anticarcinogenic mechanisms of these chemopreventive agents. Rats were maintained on AIN-76A chow or supplemented with 0.4% UDCA or F(6)-D(3) (2.5 nmol/kg chow) and treated weekly with AOM 20 mg i.p./kg wt or saline x 2 weeks. F(6)-D(3) was continued for an additional 2 weeks and UDCA for the duration of the study. At 40 weeks, animals received bromodeoxyuridine (BrdUrd) i.p. 2 h before sacrifice. A portion of each tumor was fixed in formalin and the remainder flash frozen. Colons were divided longitudinally and half-fixed in formalin and half in ethanol. The size and location of methylene blue-stained ACF were recorded. Cell proliferation (BrdUrd labeling) and apoptosis (terminal deoxynucleotidyl transferase-mediated nick end labeling assay) were measured in colonic crypts and tumors. Protein expression levels of several regulators of cell proliferation were analyzed by immunostaining and Western blotting. Colonic crypt cyclin D1 and E-cadherin mRNA levels were measured by real-time PCR. In saline injected controls, neither UDCA nor F(6)-D(3) alone had any effect on cytokinetic parameters or on the expression of mitogenic regulators. AOM significantly increased the proliferation (percentage of BrdUrd-positive cells) of both ACF (23.1 +/- 1.7%) and non-ACF crypts (17.6 +/- 1.6%), compared with normal colonic crypts (4.5 +/- 0.8%; P < 0.05). This hyperproliferation was accompanied by a 5-fold increase in cyclin D1 and >50% decrease in E-cadherin protein (P < 0.05) in ACF, both of which are predicted to be growth-enhancing alterations. UDCA and F(6)-D(3) significantly (P < 0.05) inhibited AOM-induced crypt cell hyperproliferation, ACF development, and tumor burden. These chemopreventive agents also significantly blocked AOM-induced alterations in cyclin D1 and E-cadherin protein in ACF and tumors. In ACF, changes in mRNA levels of cyclin D1, but not E-cadherin, paralleled alterations in protein expression. Cyclooxygenase-2 and inducible nitric oxide synthase were increased in AOM tumors but not in ACF, and these changes were blocked by UDCA and F(6)-D(3). UDCA and F(6)-D(3) significantly inhibited ACF development and hyperproliferation, in part, by preventing carcinogen-induced alterations in cyclin D1 and E-cadherin. In established tumors, UDCA and F(6)-D(3) also limited inductions of cyclooxygenase-2 and inducible nitric oxide synthase, which together with their effects on cyclin D1 and E-cadherin, contribute to their chemopreventive actions.     

EPI vaccination in Nepal

A number of surveys, small or large, have been undertaken by various agencies for coverage evaluation of immunization programs. The most commonly used design is the WHO-30 cluster sampling method. Other new methods are the Institute for Refresh Medical Statistics (IRMS) New Delhi method and the lot quality assurance sampling method. This paper describes the National Immunization Day (NID) method to evaluate the immunization coverage of the Expanded Program on Immunization (EPI) vaccines in the Sunsari district of Nepal. A total number of 3,332 respondents (69.4% females and 30.6% males) were interviewed regarding the immunization status of their children during NID. The children with complete immunization (BCG, measles and three doses of DPT and OPV) were 65.7%. The individual coverage by EPI vaccines (except OPV III and measles) was more than 80%. The result shows that there is positive relationship between immunization coverage and educational level of the respondents.     

Brain tumours in children

A 10 years old, female patient presented with symptoms of abnormal movement of the body for 5 years, deviation of mouth to left side for 12 days and difficulty in walking for 12 days. We report a very rare case of Brain Stem gliomas. Clinical and imaging findings were suggestive of Brain Stem gliomas. Key words: Brain tumors, Intracranial space occupying lesion.     

Bilateral lacrimal sac mucocele with punctal and canalicular atresia

Congenital absence of lacrimal puncta may be an isolated finding or associated with other developmental abnormality. Nasolacrirnal ducts can be absent thus predisposing to the formation of a congenital lacrimal mucocele. Punctal and canalicular agenesis is very rare. Four percent of new patients attending the lacrimal clinic at Moorfields Eye Hospital, London, UK. from 1981 to 1990 inclusive were diagnosed to have this condition. We describe a case of bilateral congenital absence of lacrimal puncta with lacrimal mucocele. Combined surgery was carried out by Ophthalmologist and Otolaryngologist with successful results.     

Safety of oral iron chelator deferiprone in young thalassaemics

Deferiprone is now widely used for iron chelation in patients with thalassaemia. Studies on its efficacy and safety have largely included older children and adults. OBJECTIVE: To assess the safety of deferiprone in children <6 yr of age. METHODS: The study is based on scrutiny of follow-up data of 44 patients of age <6 yr receiving deferiprone for a variable period of time. Occurrence of various side effects including gastrointestinal, osteoarticular were noticed and complete blood counts were performed every 2-4 wk. RESULTS: Nausea and vomiting were noticed in 12 (27.2%), joint symptoms were reported by four (9.1%) and neutropenia was observed in only two patients (4.5%). None of the patient had agranulocytosis. Thrombocytopenia was observed in 20 patients (45.45%), which occurred 3 months to 1 yr after deferiprone therapy. Interruption of deferiprone for 2-4 wk led to reversal of symptoms in all but two patients. CONCLUSION: Thrombocytopenia is one of the major side effects in young thalassaemics and necessitates frequent close monitoring of blood counts but its resolution after discontinuation and absence of clinical evidence of bleeding does not preclude its use.     

Spinal myelopathy induced by subarachnoid batrachotoxin: Ultrastructure and electrophysiology

A combined structural and electrophysiologic analysis on the effects of subarachnoid injections of batrachotoxin was conducted in rats. Swelling of neuronal perikarya, accompanied by areas of clearing, satellitosis, fatty metamorphosis and central chromatolysis were demonstrated in the spinal anterior horns. Studies on isolated extensor digitorum longus (fast) and soleus (slow) muscles showed membrane depolarization in the extensor 24 h after injection, with progressive augmentation of this phenomenon in animals given multiple injections of the toxin. Differential sensitivity of fast and slow muscles was evident: soleus was only slightly affected. Subarachnoid injections of batrachotoxin, which induced swelling of neuronal perikarya and axonal processes, also caused signs of denervation in the extensor muscle 7 days after injection, while spontaneous transmitter release was still present. Some structural and most electrophysiologic alterations after batrachotoxin injections were reversible.     

A prospective randomized comparison of type of nephrostomy drainage following percutaneous nephrostolithotomy: large bore versus small bore versus tubeless

PURPOSE: We compared postoperative outcomes among tubeless, conventional large bore nephrostomy drainage and small bore nephrostomy drainage following percutaneous nephrostolithotomy (PCNL) in a prospective randomized fashion. MATERIALS AND METHODS: Between January and June 2001, 30 patients undergoing PCNL were randomized to receive conventional large bore (20Fr) nephrostomy drainage (group 1, 10 patients), small bore (9Fr) nephrostomy drainage (group 2, 10 patients) or no nephrostomy drainage (group 3, 10 patients). Inclusion criteria included a single subcostal tract, uncomplicated procedure, normal preoperative renal function and complete stone clearance. Factors compared among the 3 groups were postoperative analgesia requirement, urinary extravasation, duration of hematuria, duration of urinary leak, decrease in hematocrit and hospital stay. RESULTS: The postoperative analgesic requirement was significantly higher in group 1 (217 mg) compared to groups 2 (140 mg, p <0.05) and 3 (87.5 mg, p <0.0001). Patients in group 3 had a significantly shorter duration (4.8 hours) of urinary leak through the percutaneous renal tract compared to patients in groups 1 (21.4 hours, p <0.05) and 2 (13.2 hours, p <0.05). Hospital stay was significantly shorter in group 3 (3.4 days) compared to groups 1 (4.4 days, p <0.05) and 2 (4.3 days, p <0.05). All 3 groups were similar in terms of operative time, duration of hematuria and decrease in hematocrit. Postoperative ultrasound did not reveal significant urinary extravasation in any case. CONCLUSIONS: Tubeless PCNL is associated with the least postoperative pain, urinary leakage and hospital stay. Small bore nephrostomy drainage may be a reasonable option in patients in whom the incidence of stent dysuria is likely to be higher.     

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.     

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.