Biomedical subjects
Publications and source records attributed to A K Gupta.
It is unusual for cysticercosis to occur in the substance of the breast. Only a few cases have been described in the literature. We report a case of cysticercosis perched on fibroadenoma of breast found on surgical excision in a 35 year old Nepali woman. The patient had no discernible evidence of cysticercosis in the other organs.
Transformation with ras oncogenes results in increased radiation sur vival in many but not all cells. In addition, prenyltransferase inhibitors which inhibit ras proteins by blocking posttranslational modification radiosensitize cells with oncogenic ras. These findings suggest that oncogenic ras contributes to intrinsic radiation resistance. However, because introduction of ras oncogenes does not increase radiation survival in all cells and because prenyltransferase inhibitors target molecules other than ras, these studies left the conclusion that ras increases the intrinsic radi ation resistance of tumor cells in doubt. Here we show that genetic inactivation of K- or N-ras oncogenes in human tumor cells (DLD-1 and HT1080, respectively) leads to increased radiosensitivity. Reintroduction of the activated N-ras gene into the HT1080 line, having lost its mutant allele, resulted in increased radiation resistance. This study lends further support to the hypothesis that expression of activated ras can contribute to intrinsic radiation resistance in human tumor cells and extends this finding to the K- and N- members of the ras family. These findings support the development of strategies that target ras for inactivation in the treatment of cancer.
Polymeric micelles made of copolymer of N-isopropylacrylamide (NIPAAM), vinyl pyrrolidone (VP) and acrylic acid (AA) having cross-linkage with N,N'-methylene bis-acrylamide (MBA) were used as host carrier in which up to 30%w/w ketorolac (free acid) was entrapped to make the formulation. The lyophilised powder was used for physical characterisation. The drug entrapment was found to be about 80% and the formulation was stable for 8-10 days at room temperature. The smaller the amount of ketorolac dissolved into the micelles, the longer was the formulation shelf life. The size of the particles as measured by dynamic light scattering was found to be around 35 nm diameter at 25 degrees C. TEM picture showed spherical particles. The structure of the polymer and its morphology were characterised by FTIR, NMR and XRD measurements. IR data indicated weak interaction between polymer and ketorolac in the encapsulated system. NMR spectra indicated rigid polymer backbone with intermittent iso-propyl group in the chain. XRD spectra showed significant loss of crystallinity of the drug while being entrapped in the polymeric micelles. The release of drug in aqueous buffer (pH 7.2) from the polymeric micelles at 25 degrees C were 20 and 60% after 2 and 8 h respectively and is temperature and pH dependent. In vitro corneal permeation studies through excised rabbit cornea indicated two fold increase in ocular availability with no corneal damage compared to an aqueous suspension containing same amount of drug as in nanoparticles. The formulation showed significant inhibition of lid closure up to 3 h and PMN migration up to 5 h compared to the suspension containing non-entrapped drug, which did not show any significant effect.
Leishmania amastigotes have been detected in the peripheral blood smears of Indian kala-azar patients mostly during night. It was, therefore, thought worthwhile to find out whether such amastigotes could be shown in healthy subjects who did not have any symptoms by history or signs on clinical examination. Leishmania-stained blood smears of 450 asymptomatic healthy individuals residing in an endemic village in Bihar (India) were examined by oil-immersion microscopy for the detection of amastigote, six people (1.3%) showed the presence of Leishmania amastigotes. Given the low sensitivity of a single smear examination it is likely that a much greater proportion of asymptomatic persons had parasitemia than the observed 1.3%. This finding is important from the point of view of transmission of disease, as also for modifying the current control measures.
The nitrogen fixing cyanobacterium Nostoc muscorum has been found to be sensitive to the herbicide SAN 6706 [4-chloro-5 (dimethylamino)-2-(a,a,a,-trifluoro-m-tolyl)-3-(2H) pyridazinon] at 30-45 microM within 15 min. The toxicity was more severe in combined nitrogen-free (Ncomb-free) medium than in a combined nitrogen medium; this enhancement was reversible by supplementation of the medium with 3 mM glucose or 5 microM ATP, serving as carbon and/or energy source in this organism. A mutant of this cyanobacterium resistant to 3 mM SAN 6706 has been isolated and characterized to perform nitrogenase activity in exogenous ATP supplemented Ncomb-free medium. However, it exhibited a moderate growth in combined nitrogen media in the absence of external ATP. The resistance factor is higher than 100. Simultaneously, this strain possesses a cross-resistance to methylamine, a well-known inhibitor of photophosphorylation, irrespective of the exogenous ATP supply. The behavior of the mutant suggests a defective phosphorylation in its photosynthetic system.
Head injury is associated with complex pathophysiological changes in metabolism. The objective of the study was to investigate these changes by applying on-line bedside monitoring of cerebral metabolism using microdialysis. Following approval by the Local Ethics Committee and consent from the next of kin, a microdialysis catheter was inserted into the frontal cortex of patients with severe head injury. Twenty-one patients were studied for 102.3 +/- 26.9 hours (mean +/- 95% confidence interval; total 89.4 patient monitoring days). The overall cerebral glucose (mean of means) was 1.63 +/- 0.31 mM with periods of undetectable glucose recorded. The cerebral lactate and lactate/pyruvate ratio were 4.69 +/- 0.61 mM and 29.9 +/- 3.73 respectively. Patients who died (n = 4) or who were severely disabled (not proceeding to rehabilitation, n = 5) had a tendency towards lower glucose (1.39 +/- 0.35 mM), higher lactate (5.10 +/- 1.02 mM) and higher lactate/pyruvate ratios (35.5 +/- 7.67) compared to patients with good outcome (home or proceeding to rehabilitation, n = 12, glucose 1.80 +/- 0.49 mM, lactate 4.38 +/- 0.85 mM, lactate/pyruvate ratio 27.9 +/- 4.33). Trends in these metabolic parameters relating to outcome were identifiable. In the majority of patients, cerebral glutamate levels (overall mean of means 9.47 +/- 4.59 microM) were initially high and then declined to stable levels. Patients in whom the glutamate level remained elevated or in whom secondary rises in glutamate were seen had a poor outcome. The application of bedside analysis of microdialysis enables the progress of the patient to be monitored on-line. In addition to establishing trends of improving and deteriorating metabolism, the technique has the potential to monitor the effects of therapeutic manoeuvres on the biochemistry.
Routine maternal ultrasonography (US) has revealed a very high incidence of fetal hydronephrosis (HDN), the postnatal outcome and management protocols of which are replete with controversies. Pelviureteric junction (PUJ) obstruction is the commonest postnatal diagnosis, and its management has no consensus to date. This study was carried out to define the postnatal outcome and natural history of fetal HDN and to identify the mode of management to be adopted to the best advantage. All patients were subjected to US 48 h postnatally or at first presentation and isotope renography (DTPA) with nuclear glomerular filtration rate (GFR) was carried out at 3-4 weeks of age or at presentation. Micturating cystourethrography (MCU) and/or direct radionuclide cystography (DRCG) were done in cases with bilateral HDN, nonobstructive HDN, dilated ureter on US, and recurrent urinary tract infection. Patients were then grouped for surgical intervention or conservative follow-up. Investigations were repeated periodically. A total of 56 patients were registered for the study (78 renal units) with a mean follow-up period of 14.6 months; 37 renal units were operated upon or scheduled for surgery and 67 had some organic pathology, of which PUJ obstruction was the commonest. Among patients with PUJ obstruction, indications for surgery included symptoms, a palpable mass, poor or deteriorating function, and a solitary functioning kidney. Patients operated upon showed improvement in function and/or drainage, while those followed conservatively remained stable or improved. Controversy still exists as to the optimal management of PUJ obstruction detected antenatally. While it is the commonest postnatal diagnosis, many other pathologies are now being encountered. In antenatally-diagnosed HDN, there is a good scope for conservative management provided rigid follow-up can be ensured, especially because a good recovery potential exists followed surgery whenever indicated.
The content of free sugars and the activities of enzymes involved in carbon metabolism-sucrose synthase, acid and alkaline invertase, phosphoenol pyruvate carboxylase, malic enzyme and isocitrate dehydrogenase were determined during seed development in mungbean pods. A decrease in carbohydrate content of pod wall from 10 to 25 days after flowering (DAF) and a concomitant increase in the seed till 20 DAF was observed. Sucrose remained the dominant soluble sugar in the pod wall and seed. In the branch of inflorescence and pod wall, the activities of sucrose metabolizing enzymes, viz. acid and alkaline invertase, sucrose synthase (synthesis and cleavage) and sucrose phosphate synthase were higher at 5-10 DAF, whereas in seed the maximum activities of these enzymes were observed at the time of maximum seed filling stage (10-20 DAF). High activities of sucrose synthase at the time of rapid seed filling can be correlated to its sink strength. Higher activities of phosphoenol pyruvate carboxylase in the branch of inflorescence and pod wall than in seed may indicate the involvement of the fruiting structure for recapturing respired CO2. High activities of isocitrate dehydrogenase and malic enzyme in the seed at the time of rapid seed filling could provide NADPH and carbon skeletons required for the synthesis of various seed reserves.
In approximately one third of dermatology patients, the effective management of a skin condition also involves consideration of associated emotional and psychosocial factors. Psychotropic drugs are an important part of the dermatologist's therapeutic armamentarium. This article reviews some of the salient pharmacologic guidelines and important drug-drug interactions involved in the use of the major classes of, for example, antidepressants and antipsychotic drugs, in the dermatologic patient.
Many filamentous cyanobacteria fix atmospheric nitrogen under natural conditions in specialized anaerobic compartments, heterocysts, interspersed between vegetative cells, which provide protection to the O2-sensitive nitrogenase. A few unicellular cyanobacterial strains are also known to fix nitrogen aerobically at a slower rate. Filamentous cyanobacteria lacking heterocysts are not known so far to fix nitrogen. We describe the isolation and purification of a non-heterocystous filamentous cyanobacterium from the fronds of the water-fern Azolla, fixing nitrogen at 18.7+/-0.2 n moles ethylene microg Chl. a(-1) h(-1) when grown in nitrogen-free medium at a low level of oxygen between two layers of agar. This strain of Anabaena azollae has been designated as het- nif+ (non-heterocystous and nitrogen-fixing), and is found to be easily and effectively preserved in nitrogen-free medium in standard synthetic cyanobacterial nutrient medium (pH 8.5) at a continuous light intensity of 2800 lx at 25+/-1 degrees C. This het- nif+ strain is an effective donor of the nif+ marker to a het+ nif- strain of another cyanobacterium, Nostoc muscorum, when both are grown together in a recombination study.
PURPOSE: To compare central dialysis catheter patency rates after stripping procedures with those after urokinase (UK) infusion. MATERIALS AND METHODS: Fifty-seven tunneled catheters with either (i) flow rates less than 250 mL/min and established baseline flow rates > or = 300 mL/min or (ii) flow rates 50 mL/min less than higher established baseline flows were prospectively randomized to undergo stripping procedures (n = 28) or UK infusion (n = 29) at 30,000 U/h via each port concurrently, for a total 250,000 U. Success and patency were determined by dialysis at normal flow rates (> or = 300 mL/min) or at the previously established higher baseline rate. Flow rates were monitored weekly. Primary patency ended with catheter malfunction or removal. Kaplan-Meier survival analysis was used to construct survival curves. RESULTS: In the stripping group, initial clinical success was 89% (25 of 28). The 15-, 30-, and 45-day primary patency rates were 75% (n = 20), 52% (n = 13), and 35% (n = 8), respectively. The median duration of additional function was 32 days (95% CI: 18-48 d). In the UK group, initial clinical success was 97% (28 of 29). The 15-, 30-, and 45-day primary patency rates were 86% (n = 21), 63% (n = 13), and 48% (n = 9), respectively. The median duration of additional patency was 42 days (95% CI: 22-153 d). The Wilcoxon test for equality detected no significant difference in the survival curves for the two treatment groups (P = .236). CONCLUSION: There is no significant difference in time to primary patency between the two methods. Both allow temporary catheter salvage in most patients.
Fifty-five strains, either authentic or ex-type, of seven Malassezia species were investigated for in vitro susceptibility to various concentrations (0.03-64.0 microg/mL) of three azole drugs, ketoconazole, voriconazole and itraconazole, as well as the allylamine terbinafine, using the agar dilution method. All strains of the seven Malassezia species were susceptible to the three azole drugs at low concentrations. M. furfur, M. sympodialis, M. slooffiae, M. pachydermatis, M. globosa, M. obtusa and M. restricta were most sensitive to ketoconazole and itraconazole, with minimum inhibitory concentrations (MICs) ranging from < or = 0.03 to 0.125 microg/mL. The recently introduced antifungal, voriconazole, was also very effective, with MIC80 values < or = 0.03 microg/mL for 80% of strains. MICs of terbinafine against the seven Malassezia species ranged from </= 0.03 to 64.0 microg/mL. There were variations in susceptibility of the seven Malassezia species to ketoconazole, voriconazole, itraconazole and terbinafine. Strains of M. furfur, M. globosa and M. obtusa were more tolerant to terbinafine than the remaining Malassezia species; M. sympodialis was highly susceptible. M. furfur strains tested with terbinafine ranged from highly susceptible to relatively resistant. Correct identification of Malassezia species could facilitate selection of appropriate antifungal therapy.
In an open, multicentre evaluation carried out in Brazil, Canada and South Africa we have demonstrated that fluconazole 8 mg kg-1 once weekly is effective in tinea capitis caused by Trichophyton and Microsporum species. There were 61 children, aged (mean +/- SE) 5.0 +/- 0.3 years; weight (mean +/- 5.6) 20.0 +/- 0.9 kg; 41 males, 20 females; one Asian, 57 Black, one Caucasian and two Hispanic. The organisms were Trichophyton violaceum (33 patients), T. tonsurans (11) and Microsporum canis (17). The extent of tinea capitis at pretherapy was: mild (18 patients), moderate (30) and severe (13). Patients with tinea capitis due to Trichophyton species were initially treated for 8 weeks with an extra 4 weeks of fluconazole if clinically indicated. All 44 patients with tinea capitis due to Trichophyton species were completely cured (clinically and mycologically) when evaluated 8 weeks after completion of active treatment, following 8 weeks of once weekly dosing in 35 patients and 12 weeks of once weekly dosing in nine patients. In Microsporum canis tinea capitis, an extra 4 weeks was administered at week 12 in patients where it was clinically indicated at the time. Sixteen of 17 patients with M. canis tinea capitis were completely cured (clinically and mycologically) when evaluated 8 weeks following the end of treatment when given for 8, 12 and 16 weeks in 12, one and three patients, respectively. Overall, complete cure (clinical and mycological) occurred in 60 of 61 patients at follow-up 8 weeks from the end of therapy. The duration of once weekly fluconazole in the 60 patients was 8 weeks (47 patients), 12 weeks (10 patients) and 16 weeks (three patients), respectively. Clinical adverse effects consisted of a mild, reversible gastrointestinal complaint in three (4.9%) of 61 children. A laboratory abnormality with elevated liver function tests was observed in one (5.9%) of 17 patients; this was asymptomatic, and reversible. No patient discontinued therapy. The data suggest that once weekly fluconazole dosing is effective, safe and associated with high compliance when used to treat tinea capitis.
BACKGROUND: Patients who are human immunodeficiency virus (HIV) positive are predisposed to the development of infections including tinea pedis and onychomycosis. While smaller studies have been reported, there has been no large study evaluating the prevalence of onychomycosis in HIV-positive individuals, or comparing the development of onychomycosis in a typical temperate area with that in a typical tropical area. METHODS: HIV-positive individuals were evaluated at five clinics: four in Ontario, Canada and one in Sao Paulo, Brazil. The subjects were asked questions to determine the epidemiology of onychomycosis in HIV-positive individuals. The feet were examined and nail material was obtained for mycologic examination to determine the causative organism of onychomycosis. RESULTS: A total of 500 subjects were examined (415 men and 85 women; age (mean +/- SE), 39 +/- 0.4 years; 400 Canadian, 100 Brazilian). The racial origins of the Canadian patients were: Caucasian, 83.8%; Asian, 4.3%; African-American, 8.1%; Hispanic, 3.3%; American Indian, 0.3%. The Brazilian origins were: Caucasian, 68.7%; African, 18.1%; mixed race, 13.3%. Abnormal appearing nails and mycologic evidence of onychomycosis were present in 200 (40.0%) and 116 (23.2%), respectively, of 500 subjects. The prevalence of onychomycosis in the Canadian and Brazilian samples was 24.0% (96 of 400) and 20.0% (20 of 100), respectively. The projected prevalence of onychomycosis in HIV-positive individuals in Canada was 19.9% (95% CI: 16.0-23.9%) after taking into account the age and sex distribution of HIV-positive individuals in the population. When nails appeared clinically abnormal, the prevalence of onychomycosis was 50.5% (Canada, 51.3%; Brazil, 45.5%). For comparison, published data indicate that the prevalence of onychomycosis in immunocompetent individuals living in Canada is 6.9%. The clinical presentation of onychomycosis for the whole sample (n=500) was: distal and lateral subungual onychomycosis (DLSO), 20.0%; white superficial onychomycosis (WSO), 3.6%; proximal subungual onychomycosis (PSO), 1.8% (Canadian and Brazilian samples: DLSO 21.2% vs. 15.0%, WSO 3.3% vs. 5.0%, and PSO 1.5% vs. 3.0%). The distribution of the causative fungal organisms was: dermatophytes: Candida species: nondermatophyte molds, 73:2:2 (Canadian and Brazilian samples: dermatophytes 95.5% vs. 90.9%, Candida species 3.0% vs. 0%, and nondermatophyte molds 1.5% vs. 9.0%). The use of protease inhibitors, reverse transcriptase inhibitors, or oral antifungal agents did not make a significant difference in the prevalence of onychomycosis for both the Canadian and Brazilian groups. Patients with onychomycosis were aware of their abnormal appearing nails (chi2(1)=69.7, P<0.001), embarrassed by the appearance of their nails (chi2(1)=29.7, P<0.001), and took measures to hide their nails from other individuals. A higher proportion of individuals with onychomycosis experienced discomfort compared with those without the disease (chi2(1)=9.0, P=0.003). Also, individuals who experienced pain in the nail unit were more likely to have onychomycosis (risk odds ratio (ROR), 2.2; 95% CI: 1.0-4.7, P=0.05). CONCLUSIONS: The prevalence of onychomycosis in HIV-positive individuals in the sample of 500 patients was 23.2%. In the Canadian (n=400) and Brazilian (n=100) samples, the corresponding figures were 24% and 20%, respectively, with the predominant causative organisms being dermatophytes. The projected prevalence of onychomycosis in HIV-positive Canadians is 19.9%. Predisposing factors include a CD4 count of approximately 370, a positive family history of onychomycosis, a history of tinea pedis, and walking barefoot around pools. Onychomycosis can be symptomatic, a source of embarrassment, and a potential cause of morbidity.
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BACKGROUND: Onychomycosis is a relatively common condition the aetiology of which appears to be multifactorial, with both genetic and acquired factors being responsible. In our clinical practice we have observed that smokers and individuals with peripheral arterial disease may have an increased prevalence of onychomycosis compared to normal individuals. PATIENTS AND METHODS: Patients attending a vascular clinic in a hospital were asked about a history of smoking and peripheral arterial disease. The lower extremity was assessed for peripheral arterial disease. Material was obtained from toenails for mycological evaluation. RESULTS: Two hundred and fifty-four patients (male 146, female 108; age, mean +/- standard error, 66.6 +/- 0.8 years) were enrolled. Abnormal-appearing nails and onychomycosis were present in 49.2% and 22.4% of patients, respectively. Factors associated with onychomycosis included, increasing age (risk odds ratio [ROR] 1.05, P = 0.002), male gender (ROR 1.7, P = 0.09), smoking (packs per day) (ROR 1.9, P = 0.02) and peripheral arterial disease (ROR 4.8, P = 0.02). CONCLUSIONS: The factors predisposing to the development of onychomycosis are multifactorial. Both smoking (number of packs of cigarettes consumed per day) and peripheral arterial disease are independent predictors of onychomycosis. Awareness of these factors may help in the prevention of onychomycosis and the optimal management of this disease.
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