Target pressure--glaucomatologists' holey grail.
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Glaucoma, Open-Angle↗
Biomedical subjects
K Singh
Publications and source records attributed to K Singh.
Trabeculectomy with intraoperative mitomycin C versus 5-fluorouracil. Prospective randomized clinical trial.
OBJECTIVE: To evaluate the relative efficacy and safety of 5-fluorouracil (5-FU) and mitomycin C (MMC) when used as adjuncts with primary trabeculectomy in eyes not at high risk for failure. DESIGN: Prospective multicenter, randomized clinical trial. PARTICIPANTS: One hundred thirteen patients with primary open-angle, pseudoexfoliative, pigmentary, or angle-closure glaucoma undergoing primary trabeculectomy were recruited. METHODS: One eye of each patient was randomized to receive either 5-FU (50 mg/ml for 5 minutes) or MMC (0.4 mg/ml for 2 minutes). MAIN OUTCOME MEASURES: Intraocular pressure (IOP), visual acuity, complications, and interventions were documented at fixed intervals after surgery. The study also examined progression of visual field loss, long-term complications, and bleb appearance 3 years after surgery. RESULTS: Of the 108 patients with complete perioperative information, 54 eyes received 5-FU and 54 received MMC. The proportion of patients reaching different predefined target IOPs after surgery was slightly higher in the MMC group than in the 5-FU group. This difference was less than 25%, which would have been necessary to achieve statistical significance with a power of 0.8 and the sample size used. Likewise, there was no statistically significant difference between the groups with regard to mean preoperative IOP, complications, or interventions. Mean postoperative follow-up was 309 and 330 days in the 5-FU and MMC groups, respectively (P = 0.593). CONCLUSIONS: 5-Fluorouracil and MMC were found to be equally safe and effective adjuncts to primary trabeculectomy in the short- and medium-term postoperative periods.
Aged↗
Syntheses and biological evaluation of 3-substituted amino-1-aryl-6-hydroxy-hex-2-ene-1-ones as antioxidant and hypolipidemic agents.
A new series of compounds belonging to 3-substituted amino-1-aryl-6-hydroxy-hex-2-ene-1-ones (4-12a-e) have been synthesized and evaluated for antioxidant and hypolipidemic activities. Amongst all the synthesized compounds, seven compounds, namely 5b, 5d, 6e, 8a, 8b, 10b and 11a, exhibit better antioxidant activity than probucol. Two compounds, 5d and 10b, have been evaluated in detail for antioxidant and hypolipidemic activities and show comparable activity profile to that of probucol and guggulipid. From the present study it may be postulated that the mechanism of action of these compounds could be through activation of lecithin cholesterol acyltransferase (LCAT), liver lipolytic activity, increased faecal bile acid secretion and inhibition of hepatic cholesterol biosynthesis.
Alkenes↗
Structure-activity relationship of piperine and its synthetic analogues for their inhibitory potentials of rat hepatic microsomal constitutive and inducible cytochrome P450 activities.
Inhibitors of drug metabolism have important implications in pharmaco-toxicology and agriculture. We have reported earlier that piperine, a major alkaloid of black and long peppers inhibits both constitutive and inducible cytochrome P450 (CYP)-dependent drug metabolising enzymes. In the present study, an attempt has been made to prepare several novel synthetic analogues so as to relate various modifications in the parent molecule to the inhibition of CYP activities. Two types of mono-oxygenase reactions arylhydrocarbon hydroxylase (AHH) and 7-methoxycoumarin-O-demethylase (MOCD) have been studied. Inhibition studies were investigated in rat microsomal fraction prepared from untreated, 3MC- and PB- treated rat liver in vitro. Modifications were introduced into the piperine molecule: (i) in the phenyl nucleus, (ii) in the side chain and (iii) in the basic moiety. Thus, 38 compounds have been subjected to such studies, and simultaneously an attempt has also been made to arrive at the structure-activity relationship of synthetic analogues. In general, most of the inhibitory potential of the parent molecule is lost with modification in either of the three components of piperine. Saturation of the side chain resulted in significantly enhanced inhibition of CYP while modifications in the phenyl and basic moieties in few analogues offered maximal selectivity in inhibiting either constitutive or inducible CYP activities. Thus few novel analogues as CYP inactivators have been synthesized which may have important consequences in pharmacokinetics and bioavailability of drugs.
Alkaloids↗
Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.
A novel sequence discovered in a computational screen appears distantly related to the p35 subunit of IL-12. This factor, which we term p19, shows no biological activity by itself; instead, it combines with the p40 subunit of IL-12 to form a novel, biologically active, composite cytokine, which we term IL-23. Activated dendritic cells secrete detectable levels of this complex. IL-23 binds to IL-12R beta 1 but fails to engage IL-12R beta 2; nonetheless, IL-23 activates Stat4 in PHA blast T cells. IL-23 induces strong proliferation of mouse memory (CD4(+)CD45Rb(low)) T cells, a unique activity of IL-23 as IL-12 has no effect on this cell population. Similar to IL-12, human IL-23 stimulates IFN-gamma production and proliferation in PHA blast T cells, as well as in CD45RO (memory) T cells.
Amino Acid Sequence↗
Clostridium difficile toxin and faecal lactoferrin assays in adult patients.
Clostridium difficile is the primary aetiological agent of antibiotic-associated diarrhoea. The faecal lactoferrin (FL) assay is a simple in vitro test which is highly sensitive to the presence of a marker of polymorphonuclear cells. We evaluated the use of the FL assay in conjunction with the C. difficile toxin assay in faecal samples obtained from 231 adult patients. The relationship between C. difficile toxin and FL in both negative and positive status was highly significant statistically (P < 0.001). Therefore, the FL assay performed simultaneously with the C. difficile toxin assay can help rule out asymptomatic carriage of C. difficile.
Adolescent↗
Intravenous iron polymaltose complex for treatment of iron deficiency anaemia in pregnancy resistant to oral iron therapy.
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Adult↗
Patient-oriented learning: a review of the role of the patient in the education of medical students.
AIM: To explore the contribution patients can make to medical education from both theoretical and empirical perspectives, to describe a framework for reviewing and monitoring patient involvement in specific educational situations and to generate suggestions for further research. METHODS: Literature review. RESULTS: Direct contact with patients can be seen to play a crucial role in the development of clinical reasoning, communication skills, professional attitudes and empathy. It also motivates through promoting relevance and providing context. Few studies have explored this area, including effects on the patients themselves, although there are examples of good practice in promoting more active participation. CONCLUSION: The Cambridge framework is a tool for evaluating the involvement of patients in the educational process, which could be used by curriculum planners and teachers to review and monitor the extent to which patients are actively involved. Areas for further research include looking at the 'added value' of using real, as opposed to simulated, patients; more work on outcomes for patients (other than satisfaction); the role of real patients in assessment; and the strengths and weaknesses of different models of patient involvement.
Clinical Competence↗
Budd-Chiari syndrome: our experience of 71 patients.
BACKGROUND: Hepatic venous outflow obstruction (Budd-Chiari syndrome) is frequently encountered as a cause of portal hypertension at our centre. METHODS AND RESULTS: We studied the clinical presentation, therapeutic modalities and outcome of 71 patients with hepatic venous outflow obstruction between 1992 and 1997. Twenty-seven patients presented with acute disease, while 44 had chronic presentation. Abdominal pain, distension, jaundice and upper gastrointestinal bleeding were the commonest presenting symptoms. The majority of patients had distended veins, hepatomegaly, splenomegaly, ascites and ankle oedema. The diagnosis was made on the basis of inferior vena cavography/functional hepatography and pulsed Doppler ultrasonography and/or liver biopsy in 39 patients and pulsed Doppler ultrasonography and/or liver biopsy in 32 patients. Pulsed Doppler ultrasonography accurately detected the site of the block in 31 of 39 patients (79.4%). The obstruction was in the hepatic vein in 20 patients, in the inferior vena cava in 10, and in both in 41 patients. Aetiologically, four had pregnancy-related disease, four tumour-related, three hypercoagulable states, 18 inferior vena cava membranes and 42 were idiopathic. Of 30 patients in whom liver biopsy was carried out, eight had centrizonal congestion and necrosis, 13 had mixed features and nine had established cirrhosis. Seven patients underwent a shunt operation and surgical membranotomy was carried out in one. Three patients (4.2%) died in the hospital. CONCLUSIONS: Hepatic venous outflow obstruction is a common problem; patients present with abdominal pain, distension, jaundice, distended veins, ascites and ankle oedema. Chronic presentation is more frequent. Pulsed Doppler ultrasound, venography and liver biopsy are very helpful in diagnosis.
Adolescent↗
Comparison of seven and fourteen days of lansoprazole, clarithromycin, and amoxicillin therapy for eradication of Helicobacter pylori: a report from India.
BACKGROUND: In developed countries, a 1-week regimen of combined proton pump inhibitors and two antibiotics is considered adequate for Helicobacter pylori eradication. However, there is a paucity of reports from developing countries on treatment duration of less than 14 days. We compared efficacy of 7 and 14 days of lansoprazole (L), clarithromycin (C), and amoxicillin (A) combinations for eradication of H. pylori. PATIENTS AND METHODS: Forty-six consecutive patients who presented with upper gastrointestinal symptoms and tested positive for H. pylori infection were included in the study. In every patient, after performance of upper gastrointestinal endoscopy, antral biopsies were obtained. H. pylori infection was diagnosed by positive rapid urease test and identification of organisms on antral histology. Patients were randomly selected to receive lansoprazole, 30 mg once daily, plus clarithromycin, 250 mg twice daily, plus amoxicillin, 500 mg three times daily for 2 weeks (group 1; n = 24; age, 36 +/- 12 years; 18 men) or 1 week (group 2; n = 22; age, 45 +/- 15 years; 12 men). One month after completion of treatment, repeat upper gastrointestinal endoscopy was performed. H. pylori eradication was defined as absence of organism on histopathological examination of both antrum and body of stomach and negative rapid urease test. RESULTS: Eradication rate was higher in group 1 (23 of 24; 96%) as compared to group 2 (12 of 22; 54%; p <.05). One patient in group 1 had diarrhea, and one patient in group two had skin rash and itching. CONCLUSIONS: Fourteen-day therapy with lansoprazole, clarithromycin, and amoxicillin is highly effective in eradication of H. pylori. Reducing duration of therapy to 7 days significantly lowers eradication rates.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Endoscopic dilation for treatment of anastomotic leaks following transhiatal esophagectomy.
BACKGROUND AND STUDY AIMS: Anastomotic leak is a known complication after transhiatal esophagectomy (THE) and cervical esophagogastric anastomosis. Conservative management takes a long time to heal such leaks. We assessed the role of endoscopic dilation in patients with anastomotic leak following THE. PATIENTS AND METHODS: Eight consecutive patients (seven men, one woman; mean age 51) with anastomotic leak following THE were subjected to endoscopic dilation using Savary Gilliard dilators of 7-15 mm diameter. The mean interval between surgery and detection of leak was 9 days (range 5-22 days) and dilation was performed at a mean interval of 11.4 days (range 1-20 days) after detection of the leak. RESULTS: Drainage from fistulas stopped completely after 1-8 days (mean 3 days). X-ray with water soluble contrast showed closure of the fistula in all cases. Duration of follow-up ranged from 2 to 12 months. Anastomotic strictures developed in three patients. These patients required three sessions each of repeat dilation, and were alive at follow-up periods of 2, 4, and 12 months, respectively. One patient developed recurrence of growth at an anastomotic site. Four patients died because of distant metastasis. CONCLUSIONS: Bougie dilation of anastomotic sites is a safe and effective technique for the healing of anastomotic leaks following THE. However there is a need for a prospective randomized trial comparing endoscopic dilation with no dilation in patients with anastomotic leaks following THE.
Adult↗
Gastrointestinal bleeding due to worm infestation, with negative upper gastrointestinal endoscopy findings: impact of enteroscopy.
BACKGROUND AND STUDY AIMS: In cases of hookworm and roundworm infestation, chronic occult bleeding is well known, but acute gastrointestinal bleeding is rarely described. We report five patients with worm infestation who presented with acute massive gastrointestinal bleeding. PATIENTS AND METHODS: Over 1 year, we have encountered 15 patients with obscure gastrointestinal bleeding. All the patients had normal findings on upper gastrointestinal endoscopy. Push enteroscopy was performed in each patient and evaluation of the proximal 40-50 cm of the jejunum was done. RESULTS: Five patients (four men, one woman; average age 50 yr, range 40-60) had worm infestation (two hookworm, three roundworm). All the patients had gastrointestinal bleeding (five had melena, one hematemesis, and two hematochezia) for a duration of 7-14 days. Hemoglobin ranged from 2.8 to 9 g/dl. Push enteroscopy revealed fresh blood in the jejunum, multiple erosions, and hookworms in two patients and roundworms in three patients. Hookworms were retrieved endoscopically in two patients whereas roundworms could be retrieved in only one patient. All the patients were treated with mebendazole (100 mg twice a day for 3 days), iron, and folic acid. Gastrointestinal bleeding subsided in all the patients. CONCLUSIONS: In developing countries, worm infestation should be considered an important cause of obscure acute gastrointestinal bleeding. Evaluation of the jejunum using an enteroscope will result in more frequent diagnosis of worms as a cause of acute gastrointestinal bleeding which might have been classified as obscure gastrointestinal bleeding.
Adult↗
Esophagopleural fistula after endoscopic sclerotherapy in a child.
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Anti-Bacterial Agents↗
Cholangiopathy in extrahepatic portal venous obstruction. Radiological appearances.
PURPOSE: To evaluate cholangiographic abnormalities resulting from extrahepatic portal venous obstruction (EHPVO) by sonography and endoscopic retrograde cholangiopancreaticography (ERCP). MATERIAL AND METHODS: Forty-three patients with an established diagnosis of EHPVO were subjected to duplex Doppler sonography and ERCP. Of these, 8 patients had obstructive jaundice. RESULTS: Dilated common bile duct with pericholedochal varices showing a continuous type of flow pattern was seen in 5 EHPVO patients with obstructive jaundice. ERCP revealed cholangiographic abnormalities in 40 patients (93%). Extrahepatic bile ducts were involved in 100% of cases compared to intrahepatic bile ducts (57%). Abnormalities noted were contour irregularity with indentations, displacement and angulation, strictures and filling defects in the extrahepatic ductal system. Intrahepatic bile ducts showed dilatation with areas of narrowing and filling defects. CONCLUSION: Cholangiographic abnormalities are very common in patients with EHPVO, even without clinical manifestations of biliary disease. Extrahepatic bile ducts are far more often involved compared to intrahepatic bile ducts. Extrinsic compression with contour irregularity is the most common cholangiographic finding. Sonographic findings are not diagnostic. Dilated common bile duct with pericholedochal varices was seen in only 5 patients.
Adolescent↗
Role of Q190 of MuLV RT in ddNTP resistance and fidelity of DNA synthesis: a molecular model of interactions with substrates.
Gln190 of MuLV reverse transcriptase (RT) plays an important role in the catalytic mechanism of MuLV RT for its conservative and non-conservative mutant derivatives exhibit low catalytic activity. We now report that both Q190N and Q190A MuLV RTs are more efficient in their activity to incorporate ddNTPs and exhibit higher fidelity than the wild-type (WT) enzyme of DNA synthesis in both RNA- and DNA-directed reactions. To obtain some insight into the structural basis for the differential utilization of dNTP and ddNTP by the mutant enzymes, we modeled the binary and the ternary complexes of MuLV RT using corresponding HIV-1 RT structures and available structure of the fragment of MuLV RT. Q190 of MuLV RT appears to be essential for the interaction with 3'OH of dNTP. The lack of a 3'OH moiety in ddNTP does not permit the binding of ddNTPs to WT MuLV RT. However, the shorter side chain of Q190N (or A) mutant MuLV RT and the absence of 3'OH in ddNTP result in the rearrangement of hydrophobic interactions favoring the binding and limited incorporation of ddNTPs. In addition, while modeling the binary and ternary complexes of MuLV RT, we noted that in the formation of the ternary complex, an interaction of Q190 with dNTP substrate requires a shift from its interaction with the template base. This may be achieved by a small conformational change or motion of the loop between beta9 and alphaH containing Q190, which may correspond to the conformational change step requiring participation of Q190 during the catalytic reaction as reported in an earlier biochemical investigation.
Base Sequence↗
Gastroduodenal tuberculosis presenting with massive hematemesis in a pregnant woman.
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Adult↗
Diagnostic value of ileoscopy: a report from India.
Our aim was to present a report about the usefulness of ileoscopy as an adjunct to colonoscopy, as studied in India, in the face of a dearth of such reports from the developing countries and to study the role of ileoscopy in increasing the yield of diagnosis reached and modified. In a prospective study in 66 consecutive patients undergoing colonoscopy for various indications, colonoscopy/ileoscopy was performed with a forward viewing fiberoptic colonoscope. Details of ileal mucosa, time taken to reach ileum, and length of ileum intubated were noted. Of the 66 patients undergoing colonoscopy, cecum could be reached in 62, whereas ileum was successfully intubated in 57 (86.4%). In 13 (22.5%) cases, additional information was obtained. In eight (14.4%) cases, diagnosis was established on ileoscopy. Of these, two were of lower gastrointestinal (GI) bleed (typhoid ulcer and nonsteroidal antiinflammatory drug ulcer), one had lymphoma, two had tuberculosis, and three were cases of reactive arthritis with ulcers in terminal ileum. After ileoscopy, the diagnosis was altered in five (8.7%) cases. Time taken to reach ileum from cecum was 3.3 +/- 2.5 minutes and the length of examined ileum was 17.3 +/- 7.5 cm. Ileoscopy is a useful adjunct to colonoscopy that not only helps to modify the diagnosis but also established them.
Adenomatous Polyposis Coli↗
The efficacy of ECT in mixed affective states.
ECT is efficacious in the treatment of both the depressed and manic phases of bipolar disorder. While ECT is believed to be equally efficacious in the treatment of mixed affective states, to our knowledge there are no empirical studies on this issue. A chart review study was conducted to compare treatment response and clinical course in three groups of patients who received ECT in a general hospital service: bipolar depressed (n = 38), bipolar manic (n = 5), and bipolar mixed (n = 10), diagnosed by DSM-IV criteria. All three groups showed robust response rates, but the number of days of hospitalization was significantly longer in the mixed group (mean 30, SD 19.0 days) compared with the depressed group (mean 19.0, SD 10.9 days, t = 2.4, p < 0.03). There was a trend for the number of ECT treatments to be greater in the mixed compared with the depressed group. These findings indicate that patients with mixed affective states do respond well to a course of ECT, but the longer hospital stays and greater number of ECT treatments suggest that they may be more difficult to treat with ECT than patients with pure bipolar depression or bipolar mania.
Adult↗