Shigella dysenteriae type 1 with reduced susceptibility to fluoroquinolones.
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Adult↗
Biomedical subjects
S Ghosh
Publications and source records attributed to S Ghosh.
A metabolic network analysis & NMR experiment design tool with user interface-driven model construction for depth-first search analysis.
A Windows program for metabolic engineering analysis and experimental design has been developed. A graphical user interface enables the pictorial, "on-screen" construction of a metabolic network. Once a model is composed, balance equations are automatically generated. Model construction, modification and information exchange between different users is thus considerably simplified. For a given model, the program can then be used to predict all the extreme point flux distributions that optimize an objective function while satisfying balances and constraints by using a depth-first search strategy. One can also find the minimum reaction set that satisfies different conditions. Based on the identified flux distributions or linear combinations, the user can simulate the NMR and GC/MS spectra of selected signal molecules. Alternately, spectra vectorization allows for the automated optimization of labeling experiments that are intended to distinguish between different, yet plausible flux extreme point distributions. The example provided entails predicting the flux distributions associated with deleting pyruvate kinase and designing 13C NMR experiments that can maximally discriminate between the flux distributions.
Computer Simulation↗
Combination immunomodulatory therapy with cyclosporine and azathioprine in corticosteroid-resistant severe ulcerative colitis: the Edinburgh experience of outcome.
BACKGROUND: Cyclosporine is a fungal metabolite and a powerful immunosuppressant. While response to intravenous steroids in severe ulcerative colitis is in excess of 60%, the remainder of patients are left with the options of curative panproctocolectomy or administration of intravenous rescue therapy with cyclosporine. There have been conflicting reports on the efficacy of intravenous cyclosporine in acute ulcerative colitis, and there are serious concerns about potential toxicity and opportunistic infections such as Pneumocystis carnii pneumonia. There are also concerns about early relapse and colectomy following cyclosporine rescue. To date there has been a paucity of data available to help guide the gastroenterologist in the use of cyclosporine and the maintenance of remission once achieved. METHODS: Between 1994 and 2001, a total of sixteen patients who had received intravenous cyclosporine for acute exacerbation of their known UC (seven females, nine males, mean age 33 years) whose records were available for analysis. All patients were refractory to intravenous methylprednisolone (60 mg/24 h). Patients who responded to cyclosporine were discharged on a regimen of oral cyclosporine, oral steroids oral azathioprine and 5-aminosalicylate. RESULTS: Median disease duration was 5.4 years (range 0.9-25 years). All sixteen patients were initially treated with cyclosporine at a dose of 4 mg/kg/day. Nine patients were started on oral azathioprine (median dose 1.8 mg/kg). Seven patients underwent surgery (panproctocolectomy), although none had surgery after 6 months. Comparisons were made between patients with <7 days and >7 days intravenous steroid. Other parameters analysed were stool frequency at 3 days and CRP at 3 days. There were no significant differences between these groups. Median bowel frequency at day 3 was higher in patients who finally underwent surgery. At 3 years follow-up, 56% of the sixteen patients had avoided surgery by using azathioprine immunosuppression. CONCLUSION: The initial response rate to intravenous cyclosporine was high (69%). Side effects were documented in the majority of patients, but none of the patients had to discontinue treatment on account of these. Azathioprine has a useful role in maintaining the remission achieved by i.v. cyclosporine for acute ulcerative colitis patients. More than half the patients will avoid colectomy long-term when using triple immunosuppressive therapy including azathioprine adding support for its relative safety and another role for its use.
Administration, Oral↗
Experimental immunisation of crossbred cattle with glycoproteins isolated from the larvae of Hyalomma anatolicum anatolicum and Boophilus microplus.
In India, control of tick infestations is a major problem facing the owners of highly productive crossbred cattle. To develop suitable immunoprotective measures against the multitick infestations, specific problem encountered by the Indian farmers, an attempt has been made to identify candidate protein molecules in the larvae of Hyalomma anatolicum anatolicum and Boophilus microplus. Employing two steps affinity chromatography method, glycoproteins of 34 and 29 kDa were isolated from H. a. anatolicum and B. microplus, respectively. The additive effect of the isolated glycoproteins was tested by the immunisation of crossbred male calves at a dose of 200 microg/animal of each glycoprotein, three divided dosages. Following challenge infestations by the stages of two species of ticks, a significant rejection of (73.6%; P < 0.01) of larvae and adults (75.0%; P < 0.01) of H. a. anatolicum and adults (89.8%; P < 0.01) of B. microplus were noted. The direct effect of immunisation on the stages of the challenged ticks (%DT) was calculated as 69%, 52% against larvae and adults of H. a. anatolicum and 60% against adults of B. microplus. A direct corelation between protection and anti-glycoprotein antibody titre was detected. The effect of the isolated glycoproteins on limiting the tick infestation is discussed in detail.
Animals↗
Bobble-head doll syndrome: some atypical features with a new lesion and review of the literature.
Bobble-head doll syndrome is a rare and unique movement disorder encountered in children. It is characterized by continuous or episodic involuntary forward and backward and side to side movement of the head at the frequency of 2-3 Hz. Neuroimaging in most of the cases reveals third ventricular tumors, suprasellar arachnoid cysts, aqueductal stenosis and other lesions in the region of the third ventricle along with communicating hydrocephalus. In most of the circumstances, the problem starts in the first decade of life and diversion of cerebrospinal fluid by shunt operation is very often accompanied by dramatic improvement. We report one case where bobbing of the head started at around 12 years of age. Additionally, there was evidence of partial left abducens nerve palsy, tremor in the outstretched hands, difficulty in finger-nose test and tandem walking, hyperreflexia and extensor plantar response. He was unconscious on two occasions and there was evidence of gross hydrocephalus along with a thin membranous web, running transversely across the lower part of the aqueduct of Sylvius without any cerebrospinal fluid flow void. Ventriculo-peritoneal shunt abolished the abnormal movements. We propose that the aqueductal web was the offending agent for the pathogenesis of bobble-head doll syndrome in our case and this lesion has not been identified in the cases reported so far. Relevant literature in this regard has also been reviewed.
Adolescent↗
Sinonasal aspergillosis in immunocompetent Indian children: an eight-year experience.
A retrospective study of 40 otherwise healthy children suffering from paranasal aspergillosis is presented. Fifteen percentage of this group was under 10 years of age. The clinical characteristics were marked facial deformity, orbital involvement (52.5%) and skull base erosion (12.5%). Ethmoid sinus was the commonest sinus to be affected. Aspergillus serology was positive in 35% and fungal culture grew the organism in 40%. Histopathology revealed allergic or non-invasive fungal infections without any tissue invasions. Surgery was performed in all except one case. Recurrence was 15% treated by revision surgery and antifungal therapy.
Adolescent↗
Marginally excised parotid pleomorphic salivary adenomas: risk factors for recurrence and management. A 12.5-year mean follow-up study of histologically marginal excisions.
The aim of the study was to identify recurrence risk factors in surgically excised parotid pleomorphic salivary adenomas. We reviewed the case histories and histological findings for all cases of marginal or inadequate excision of pleomorphic salivary adenomas at the Royal Hallamshire Hospital, Sheffield, UK, between 1980 and 1995. A total of 83 cases with complete records were identified, with a mean follow-up period of 12.5 years. The histological slides were reviewed in each case. The overall recurrence rate was 6.0%. Where tumour was present at the margin, recurrence occurred in 17.6% of cases. However, cases conventionally regarded as marginally excised and likely to recur (tissue margin < 1 mm) showed recurrence in only 1.8% of cases. Intraoperative capsular rupture, microscopic capsular invasion by tumour and several other surgical factors were not predictive of recurrence. Adequate excision of pleomorphic salivary adenomas, in the sense of minimal recurrence risk, does not require more than a fraction of a millimetre of surrounding tissue. Only pleomorphic salivary adenomas with tumour actually at the excision margin require prolonged follow-up or consideration of radiotherapy. Provided that the tumour can be removed intact, the surgical approach for pleomorphic salivary adenomas should be guided by the need to preserve vital structures rather than by an attempt to remove a cuff of normal tissue with the tumour.
Adenoma, Pleomorphic↗
A study of recurrence of retraction pockets after various methods of primary reconstruction of attic and mesotympanic defects in combined approach tympanoplasty.
The major drawback of combined approach tympanoplasty (CAT) is a relatively high rate of cholesteatoma recurrence compared to open-cavity techniques, which is thought to occur primarily by recurrence of retraction pockets. In this series of 63 CATs carried out by one surgeon, scutum reconstruction to prevent recurrent attic retraction was carried out in 43 cases. Repair with bone pate proved much more successful in achieving this (20.7%; 6/29 recurrent retraction pockets) compared to tragal cartilage (57.1%; 8/14) (Fisher's exact test, P = 0.0205) and was found to be a result of the greater incidence of cartilage resorption. Recurrence of retraction in pars tensa defects was more common as the only material used was a simple temporalis fascia graft. The mean time to development of recurrences was 21.1 months and that has important implications for follow-up. We conclude that the use of bone pate for scutum reconstructions reduces the incidence of attic retraction pockets, and therefore the risk of cholesteatoma recurrence following CAT.
Adolescent↗
Tomato and garlic can modulate azoxymethane-induced colon carcinogenesis in rats.
Tomato (Lycopersicon esculentum) and garlic (Allium cepa) are important constituents of the human diet. Compounds like diallyl sulfides, diallyl disulfides and quercetin, which are active components of garlic, have known anti-inflammatory, antimutagenic activities. Similarly, active components in tomato, such as kaempferol and chlorogenic acid, have antimutagenic activities and lycopene is the most active oxygen quencher with potential chemopreventive activities. In view of this, an endeavour was made to evaluate the anticarcinogenic effect, if any, of tomato and garlic consumption individually and in combination on azoxymethane-induced colonic precancerous lesion, the aberrant crypt foci in animal model. Sprague-Dawley rats (4-5 weeks old) were injected with azoxymethane (15 mg/kg b.w.) and orally administered with 2% (w/v) of tomato, garlic and a combination of both. After 12 weeks of first azoxymethane injection, colons were assessed for aberrant crypt foci and compared with the carcinogen control group. Lipid peroxidation level and glutathione-S-transferase (GST) activity were assessed in liver as well as in colon. Furthermore, in situ cell proliferation and apoptosis were estimated using the Brdu incorporation method and TUNEL method respectively. It was observed that aberrant crypt foci were reduced in all treated groups (by 32.11% in garlic, by 76.14% in tomato and by 55.96% in the combination group). Among treated groups, GST activity was found to be induced in both liver and colon, whereas considerable reduction in lipid peroxidation level was observed in liver as well as in colon with respect to the carcinogen control group. Significant reduction in Brdu labelling index and increase in apoptotic index in colon was noted in the treated groups. These results suggest that tomato and garlic suspensions have a protective effect on colon carcinogenesis, which is mediated by modulation of different biological pathways during carcinogenesis.
Animals↗
Alpha 4 integrin blockade in inflammatory bowel disease.
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Antibodies, Monoclonal↗
Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial.
BACKGROUND: Tumour necrosis factor production is increased in the mucosa of patients with active ulcerative colitis. The benefits of infliximab in Crohn's disease are established. We investigated its efficacy in ulcerative colitis. METHODS: We conducted a randomised placebo controlled trial of infliximab (5 mg/kg) in the treatment of glucocorticoid resistant ulcerative colitis. Infusions were given at weeks 0 and 2. Disease activity and quality of life were recorded over eight weeks of follow up. Remission was defined as an ulcerative colitis symptom score (UCSS) of < or =2 and/or Baron score of 0 at week 6. Patients not in remission were offered open label infliximab 10 mg/kg and reviewed two weeks later. RESULTS: After two weeks, there was no statistically significant difference between the infliximab and placebo groups in the proportion of patients with a Baron score of 0 (13% (3/23) v 5% (1/19) (95% confidence interval (CI) -9% to 24%); p=0.74). After six weeks, remission (UCSS < or =2) rates were 39% (9/23) versus 30% (6/20) (95% CI -19 to 34%; p=0.76). The median improvement in UCSS was 3 for the infliximab group and 2.5 for the placebo group (p=0.82, Mann-Whitney U test). A Baron score of 0 was likely in either group (26% (6/23) v 30% (6/20) (95% CI -30% to 23%); p=0.96). Improvement in the IBDQ and EuroQol was not significantly different between the groups (p=0.22 and 0.3, respectively, Mann-Whitney U test). Twenty eligible patients were given open labelled infusions. Remission was achieved in 3/11 (27%) patients initially treated with infliximab and in 1/9 (11%) patients treated with placebo. CONCLUSION: These data do not support the use of infliximab in the management of moderately active glucocorticoid resistant ulcerative colitis.
Adult↗
Expression of cell surface transmembrane carbonic anhydrase genes CA9 and CA12 in the human eye: overexpression of CA12 (CAXII) in glaucoma.
PURPOSE: Carbonic anhydrase enzymes (CAs) are universally involved in many fundamental physiological processes, including acid base regulation and fluid formation and movement. In glaucoma patients, CA inhibitors are very effective in lowering intraocular pressure by reducing the rate of aqueous humour secretion mediated by the CAs in the ciliary epithelium. In this work, we investigated the expression and tissue distribution of two recently discovered CA genes CA9 (CAIX) and CA12 (CAXII) in fetal, neonatal, and adult human eyes with and without glaucoma. METHODS: CAIX and CAXII expression in 16 normal and 10 glaucomatous eyes, and in cultured non-pigmented ciliary epithelial cells (NPE) from normal and glaucoma eye donors was assessed by immunostaining. In addition, northern blot hybridisation was performed to assess expression of CA4, CA9, and CA12 mRNA in cultured NPE cells from normal and glaucoma donors. RESULTS: CAXII was localised primarily to the NPE with its expression prominent during embryonic eye development but which decreased significantly in adults. CAIX expression in the NPE was very low. The epithelium of cornea and lens occasionally expressed both enzymes at low levels during development and in adult eye, and no expression was detected in the retina. The NPE from glaucoma eyes expressed higher levels of CAXII, but not CAIX, in comparison with normal eyes. This expression pattern was retained in cultured NPE cell lines. NPE cells from a glaucoma patient showed a five-fold increase in the CA12 mRNA level with no detectable expression of CA9 mRNA. Also, no expression of the CA4 gene encoding a GPI anchored plasma membrane protein was detected on these northern blots. CONCLUSIONS: Transmembrane CAIX and CAXII enzymes are expressed in the ciliary cells and, thus, may be involved in aqueous humour production. CA12 may be a targeted gene in glaucoma.
Blotting, Northern↗
Low HbA1c levels in a poorly controlled diabetic.
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Diabetes Mellitus↗
Headache in diabetes--occipital neuropathy.
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Adult↗
Effect of adrenalectomy on rat peritoneal macrophage response.
Glucocorticoid hormones are important for vital functions and act to modulate inflammatory and immune responses. In contrast to other hormonal systems no endogenous mediators have been identified that can directly counter-regulate their potent anti-inflammatory and immunosuppressive properties. Glucocorticoids are known to interfere with the ability of the macrophage not only to induce and amplify an immune response but also to inhibit macrophage inflammatory effector functions. Although the actual immunocompetence of animals undergoing endocrine gland ectomy has never been directly studied, there is no doubt that adrenal hormones are deeply involved in the development and maintenance of the immunitory functions and this may in turn influence the inflammatory reaction. To study the effect of endogenous glucocorticoids on the functions of rat peritoneal macrophages and induction of humoral immune response we observed some of the rat peritoneal macrophage effector functions, provided that endogenous glucocorticoids are depicted by adrenalectomy. The mean phagocytic index (PI) of control macrophage (Mphi) is increased from 23,825 +/- 427 to 31,895 +/- 83 after adrenalectomy (P < or = 0.001). Intracellular killing capacity in control cell is 82% which is found to be 73% in case of adrenalectomised cell (p < 0.05). The amount of nitric oxide released from control Mphi 20.25 +/- 1 microM following adrenalectomy shows the amount of nitric oxide release was 18.25 microM (p < or = 0.01 ). The percentage of DNA fragmentation in control Mphi was 68.82 +/- 4 which was reduced to 56.76 +/- 1 after adrenalectomy (p < or = 0.01). In sheep red blood cell (SRBC) immunised and adrenalectomised animal, agglutination titre was obtained at lowest antibody concentration (1 : 128) whereas serum from SRBC immunised normal rats showed early agglutination (1: 32). Endogenous glucocorticoid depleted rats show enhanced phagocytic capacity, antibody raising capacity as well as on the other hand adrenal hormone insufficiency reduces the intracellular killing capacity, nitric oxide (NO) release, improper cell maturation and heightens the probability of infection. These observations demonstrate a counter-regulatory system via glucocorticoid that functions to control inflammatory and immune responses.
Adrenalectomy↗
Impact of zinc supplementation on diarrhoeal morbidity in rural children of West Bengal, India.
AIM: To determine the role of zinc supplementation in reducing diarrhoeal morbidity in children. METHODS: A randomized, double-blind, community-based intervention study was conducted in 280 rural children aged between 6 and 41 mo. Children were randomly allocated into three groups. One group received a daily dose of 10 mg zinc for 5 d wk(-1), another group received 50 mg zinc once weekly and the remaining group received placebo. Zinc was supplemented for 16 wk from November 1999. Diarrhoeal episodes were detected by weekly surveillance during the supplementation period. RESULTS: Eighty diarrhoeal episodes were detected among 59 children in all 3 groups. The groups were compared with each other at baseline and as regard to the outcome variable (incidence of diarrhoea). The proportion of children suffering from diarrhoea during the period was significantly lower in the zinc-supplemented groups (15.8% in daily and 16.5% in weekly group) than in the placebo group (30.8%). The incidence of diarrhoea in the daily and weekly zinc-supplemented groups was 0.68 and 0.69 episodes child(-1) y(-1), and that in the placebo group was 1.67 episodes child(-1) y(-1) (relative risk 0.41, 95% confidence interval 0.24-0.71). Diarrhoeal incidence of < 4 d duration was found to occur significantly less often in the supplemented groups. There was no difference in diarrhoeal incidence between the daily and weekly zinc-supplemented children. There were no detected adverse reactions in any of the supplemented groups. CONCLUSION: The study indicates that zinc supplementation is effective in reducing diarrhoeal morbidity when administered either daily or in a weekly schedule.
Age Factors↗
Tea can protect against aberrant crypt foci formation during azoxymethane induced rat colon carcinogenesis.
Tea shows many health promoting activities including chemopreventive action during carcinogenesis due to the presence of antioxidative polyphenolic constituents. The present experiment evaluated the anticarcinogenic role of black tea infusion on azoxymethane induced colonic preneoplastic lesions, the aberrant crypt foci in Sprague-Dawley rats. Rats were injected with azoxymethane (15 mg/kg b.w.) and received oral administration of 1% and 2% (w/v) tea infusions from first day of carcinogen application. This treatment was continued for twelve weeks and assessed for aberrant crypt foci and compared with untreated carcinogen control group. Levels of lipid peroxidation were determined in liver as well as in colon tissue. During initiation phase of carcinogenesis, glutathione-S-transferase (GST) and glutathione peroxidase (GPx) activities were also evaluated. Significant reduction in the number of aberrant crypt foci and levels of lipid peroxidation among the tea-treated groups were observed. Induction of GST and GPx activities was noted during the initiation phase of carcinogenesis. Results of the present study indicate that the protective effect of black tea infusions may be due to an outcome of antioxidative influence of tea components on azoxymethane induced carcinogenesis.
Administration, Oral↗