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Biomedical subjects

S Ghosh

Publications and source records attributed to S Ghosh.

At least 487 records · Page 27Linked to original sources

Palliation of a malignant gastrocolic fistula by endoscopic human fibrin sealant injection.

We report the case of a female patient with Hodgkin's disease resistant to therapy who developed a gastrocolic fistula as a consequence of her disease, leading to distressing faeculent vomiting. This was not considered to be amenable to surgical resection and her symptoms were successfully palliated endoscopically using injection of human fibrin sealant into the gastric and colonic aspect of the fistula tract. Both mechanical sealing and promotion of healing by human fibrin sealant are likely to be responsible for its efficacy.

Adult↗

Methods for precise sizing, automated binning of alleles, and reduction of error rates in large-scale genotyping using fluorescently labeled dinucleotide markers. FUSION (Finland-U.S. Investigation of NIDDM Genetics) Study Group.

Large-scale genotyping is required to generate dense identity-by-descent maps to map genes for human complex disease. In some studies the number of genotypes needed can approach or even exceed 1 million. Generally, linkage and linkage disequilibrium analyses depend on clear allele identification and subsequent allele frequency estimation. Accurate grouping or categorization of each allele in the sample (allele calling or binning) is therefore an absolute requirement. Hence, a genotyping system that can reliably achieve this is necessary. In the case of affected sib-pair analysis without parents, the need for accurate allele calling is even more critical. We describe methods that permit precise sizing of alleles across multiple gels using the fluorescence-based, Applied Biosystems (ABI) genotyping technology and discuss ways to reduce genotyping error rates. Using database utilities, we show how to minimize intergel allele size variation, to combine data effectively from different models of ABI sequencing machines, and automatically bin alleles. The final data can then be converted into a format ready for analysis by statistical genetic packages such as MENDEL.

Alleles↗

A fundamental metric for continuity of care: modeling and performance evaluation.

The concept of continuity in medicine is fundamental and it refers to the delivery of medical care to a patient by a care provider in an uninterrupted and coordinated manner and in accordance with the medical care needs of the patient. Principal limitations of previous studies include the following. First, there is the absence of a deliberate effort to schedule a patient's successive visits with the same provider. Second, in most cases, the reported measures are derived from the data collected through questionnaires that patients and doctors are asked to complete from memory. This introduces an unreliability factor. Third, the reported continuity-related measures are restricted to the available patient sample and, as a result, they do not necessarily reflect a representative patient distribution by age in a typical community. Fourth, the relationship between the patient-doctor interaction interval and the continuity of medical care has never been explored systematically in the literature. This paper models continuity for a representative staff model health maintenance organization (HMO) clinic in suburban Arizona and simulates patient visits that are stochastically generated through utilizing representative numbers of patient visits and care providers. It focuses on individual-based continuity delivered by a primary care provider, i.e., a general practitioner. In the simulation, the visit patterns of patients, their ages, and the length of the interaction episodes are synthesized stochastically. The distributions reflect both the patient visit profile, by age, inherent in the 90,000+ patient electronic records collected at the CIGNA HMO clinic at Chandler, AZ, over a three-year period, and the population distribution inherent in the CIGNA records. A key characteristic of the model is that it aims at deliberately maximizing continuity by making a strong effort to schedule both a patient's regular visit and follow-ups with the primary care provider, subject to the provider's availability and schedule. This paper proposes a new definition of continuity, fundamental continuity of care index (FCCI), and argues that, fundamentally, a primary care provider's depth of understanding of the patient is directly proportional to the total length of interaction between the patient and the primary care provider. Utilizing the CIGNA summary data, this paper organizes patients into five age groups: 0-5 years, 5-15 years, 15-45 years, 45-60 years, and 60+ and synthesizes the corresponding arrival distributions. Performance results, obtained for a total of 55,056 patient visits over a three-year period indicate that, while 94-97% of the patient visits are with the primary care provider, patients spend 76-77% of the nominal total visit time with their primary care provider, leading to FCCI values ranging from 0.72 to 0.75. Performance results indicate that for different choices of the mean of the patient-doctor interaction duration, the average FCCI values, obtained following simulation, reveal an approximate bell-shaped graph. For values of the mean ranging from 5 to 10, 15, 20, 25, 35, 45, and 55 min, the average FCCI measure starts at 0.49, increases to a maximum of 0.88 corresponding to a mean of 25 min, and then decreases to 0.60. Thus, for a medical clinic, constrained by the number of care providers servicing a fixed number of patients, for a given population distribution by age, an optimum value for the average patient-doctor interaction duration may be obtained empirically that yields the maximal continuity measure.

Arizona↗

Metal resistance in Acidocella strains and plasmid-mediated transfer of this characteristic to Acidiphilium multivorum and Escherichia coli.

Acidophilic heterotrophic strain GS19h of the genus Acidocella exhibited extremely high resistance to CdSO4 and ZnSO4, with a MIC of 1 M for each. The respective MICs for an Acidocella aminolytica strain were 400 and 600 mM. The MICs of NiSO4 for the above strains were 200 and 175 mM, respectively. These strains were also resistant to CuSO4, the MICs being 20 and 40 mM, respectively. An Acidocella facilis strain showed resistance only to ZnSO4, with a MIC of 150 mM. The metal salts, in general, extended the lag period, log period, and generation time, with decreases in growth rate and optimum growth. A. aminolytica and strain GS19h each contain more than one plasmid, while A. facilis contains none. After transformation by electroporation with the plasmid preparation from strain GS19h, an Acidiphilium multivorum strain became highly resistant to cadmium and zinc, and the plasmid profile of the transformed cells was found to differ from that of the original Acidiphilium multivorum strain. Escherichia coli HB101 and DH5 alpha also exhibited more resistance to these metals, especially zinc, after transformation with the total plasmid preparation of strain GS19h or a 24.0-MDa plasmid of the same strain, although no plasmid was detected in the transformed cells. Thus, the results derived mainly through genetic experiments demonstrate for the first time the plasmid-mediated transfer of metal resistance for an acidophilic bacterium.

Bacteria↗

Evidence for the bacterial origin of genes encoding fermentation enzymes of the amitochondriate protozoan parasite Entamoeba histolytica.

Entamoeba histolytica is an amitochondriate protozoan parasite with numerous bacterium-like fermentation enzymes including the pyruvate:ferredoxin oxidoreductase (POR), ferredoxin (FD), and alcohol dehydrogenase E (ADHE). The goal of this study was to determine whether the genes encoding these cytosolic E. histolytica fermentation enzymes might derive from a bacterium by horizontal transfer, as has previously been suggested for E. histolytica genes encoding heat shock protein 60, nicotinamide nucleotide transhydrogenase, and superoxide dismutase. In this study, the E. histolytica por gene and the adhE gene of a second amitochondriate protozoan parasite, Giardia lamblia, were sequenced, and their phylogenetic positions were estimated in relation to POR, ADHE, and FD cloned from eukaryotic and eubacterial organisms. The E. histolytica por gene encodes a 1,620-amino-acid peptide that contained conserved iron-sulfur- and thiamine pyrophosphate-binding sites. The predicted E. histolytica POR showed fewer positional identities to the POR of G. lamblia (34%) than to the POR of the enterobacterium Klebsiella pneumoniae (49%), the cyanobacterium Anabaena sp. (44%), and the protozoan Trichomonas vaginalis (46%), which targets its POR to anaerobic organelles called hydrogenosomes. Maximum-likelihood, neighbor-joining, and parsimony analyses also suggested as less likely E. histolytica POR sharing more recent common ancestry with G. lamblia POR than with POR of bacteria and the T. vaginalis hydrogenosome. The G. lamblia adhE encodes an 888-amino-acid fusion peptide with an aldehyde dehydrogenase at its amino half and an iron-dependent (class 3) ADH at its carboxy half. The predicted G. lamblia ADHE showed extensive positional identities to ADHE of Escherichia coli (49%), Clostridium acetobutylicum (44%), and E. histolytica (43%) and lesser identities to the class 3 ADH of eubacteria and yeast (19 to 36%). Phylogenetic analyses inferred a closer relationship of the E. histolytica ADHE to bacterial ADHE than to the G. lamblia ADHE. The 6-kDa FD of E. histolytica and G. lamblia were most similar to those of the archaebacterium Methanosarcina barkeri and the delta-purple bacterium Desulfovibrio desulfuricans, respectively, while the 12-kDa FD of the T. vaginalis hydrogenosome was most similar to the 12-kDa FD of gamma-purple bacterium Pseudomonas putida. E. histolytica genes (and probably G. lamblia genes) encoding fermentation enzymes therefore likely derive from bacteria by horizontal transfer, although it is not clear from which bacteria these amebic genes derive. These are the first nonorganellar fermentation enzymes of eukaryotes implicated to have derived from bacteria.

Alcohol Dehydrogenase↗

Regulation of IkappaB beta in WEHI 231 mature B cells.

Constitutive activation of NF-kappaB in WEHI 231 early mature B cells resembles the persistent activation of NF-kappaB that is observed upon prolonged stimulation of other cells. In both cases, NF-kappaB DNA binding complexes are found in the nucleus, despite the abundance of cytosolic IkappaB alpha. Recently, we have shown that prolonged activation of 70Z/3 cells with lipopolysaccharide results in the degradation of IkappaB beta, followed by its subsequent resynthesis as a hypophosphorylated protein. This protein was shown to facilitate transport of a portion of NF-kappaB to the nucleus in a manner that protects it from cytosolic IkappaB alpha. We now demonstrate that the most abundant form of IkappaB beta in WEHI 231 cells is a hypophosphorylated protein. This hypophosphorylated IkappaB beta is found in a stable complex with NF-kappaB in the cytosol and is also detected in NF-kappaB DNA binding complexes in the nucleus. It is likely that hypophosphorylated IkappaB beta in WEHI 231 cells also protects NF-kappaB from IkappaB alpha, thus leading to the continuous nuclear import of this transcription factor.

Acetylcysteine↗

Metabolic defects in lean nondiabetic offspring of NIDDM parents: a cross-sectional study.

First-degree relatives of NIDDM patients have an approximately 40% lifetime risk of developing diabetes, and insulin resistance is the best predictor. However, insulin resistance is altered by many other factors, including age, diet, exercise, and medications. To investigate the metabolic and endocrine alterations associated with insulin resistance when all the above confounding factors are excluded, we examined the first phase of insulin secretion and insulin sensitivity in 49 white normoglycemic (4.99 +/- 0.51 vs. 4.95 +/- 0.41 mmol/l) nonexercising lean (BMI, 24 +/- 3 vs. 23 +/- 2 kg/m2; 105 +/- 3 vs. 104 +/- 3% of ideal body weight) offspring of NIDDM patients. These subjects were compared with 29 matched healthy control subjects by means of an intravenous glucose bolus (0.3 g/kg body wt), immediately followed by a euglycemic-hyperinsulinemic (approximately 420 pmol/l) clamp, along with lipid and amino acid profiles. The offspring showed fasting hyperinsulinemia (40.6 +/- 15.8 vs. 30.9 +/- 13.6 pmol/l; P = 0.005) and higher free fatty acid (FFA) levels (582 +/- 189 vs. 470 +/- 140 micromol; P = 0.007), whereas triglycerides, total cholesterol, and HDL and LDL cholesterol levels were comparable with those of control subjects. Alanine (320 +/- 70 vs. 361 +/- 73 micromol/l; P = 0.017), serine (P = 0.05), and glutamine and glycine (P = 0.02) were lower in the offspring than in the control subjects, whereas branched-chain amino acids (343 +/- 54 vs. 357 +/- 54 micromol/l; P = 0.28) were not different. Insulin sensitivity was lower (4.86 +/- 1.65 vs. 6.17 +/ 1.56 mg x kg(-1) x min(-1); P = 0.001), and an inverse correlation with fasting FFAs in the offspring (adjusted R2 = 0.21, P = 0.0005), but not in control subjects (adjusted R2 = 0.03, P = 0.368), was found. Because insulin sensitivity in the offspring appeared to be a mixture of three distributions, they were subdivided into three subgroups: very low, low, and normal insulin sensitivity (20, 47, and 33%, respectively). The same alterations in amino acid and FFA metabolism were observed in the very low and low subgroups but not in the normal subgroup. The first phase of insulin secretion appeared to compensate significantly for insulin resistance in the low subgroup versus the normal subgroup and controls, but was inappropriately low in the subgroup with very low insulin sensitivity considering its degree of insulin resistance. In conclusion, lean insulin-resistant offspring of NIDDM parents showed 1) trimodal distribution of insulin sensitivity, 2) high fasting plasma FFA concentrations, 3) an inverse correlation between insulin sensitivity and FFA concentration, 4) low plasma gluconeogenic amino acid concentrations, and 5) defective insulin secretion when related to insulin sensitivity in the subgroup of very resistant offspring. These results suggest that, in this white population, insulin sensitivity may be determined by a single major gene and that alterations in FFA metabolism may play a role in the pathogenesis of NIDDM.

Adult↗

Value of faecal leucocyte count as an indicator of invasiveness in mucoid diarrhoea.

Importance of faecal leucocyte count as an indicator of invasiveness in mucoid diarrhoea was studied. A total of 290 faecal specimen, 170 from mucoid diarrhoea and 120 from watery diarrhoea were examined for faecal leucocyte count under high power field (hpf) from rural children below four years of age during the period from November 1992 to October 1995. Faecal leucocyte count > 10/hpf was noted in 45.9% of mucoid diarrhoea as against 19.2% of watery diarrhoea (p < 0.0001) samples. From faecal samples with > 10 faecal leucocyte count, invasive pathogens could be recovered in 19 (24.5%) to none of 23 patients with watery diarrhoea (p < 0.006 Fisher exact test). This sample test appears to be of value as an indicator of invasiveness in mucoid diarrhoea in the absence of culture facility.

Child, Preschool↗

Reduced long-term survival following major peptic ulcer haemorrhage.

BACKGROUND: The late outcome of patients who present with major peptic ulcer haemorrhage is unclear. An examination was made of the hypothesis that prognosis may be poor because many such patients have severe co-morbid diseases. METHODS: Some 121 patients treated endoscopically for severe peptic ulcer haemorrhage were followed for a median of 36 (range 30-76) months and outcome was compared with that of age- and sex-matched controls. RESULTS: Thirty patients (25 per cent) died during the follow-up period and Kaplan-Meier plots showed reduced survival in patients with ulcers (P < 0.01). Death was restricted largely to patients who had co-morbid diseases. Eight of the remaining 91 patients had further peptic ulcer bleeding; two of these were taking maintenance acid-reducing therapy and only one had significant dyspepsia before rebleeding. Eighty-three per cent of surviving patients had little or no dyspepsia. CONCLUSIONS: The late prognosis of patients who present with major ulcer haemorrhage is poor, but most deaths are a consequence of co-morbid disease and not recurrent ulcer bleeding. Most patients have little dyspepsia and those who rebleed are largely free from dyspepsia.

Adult↗

Risk behavioural practices of rural mothers as determinants of childhood diarrhoea.

Maternal behaviours related to certain child care practices which possibly have a contributory role in causation of diarrhoea in children were studied. Comparison was made between behaviours of mothers in 108 families having diarrhoeal children (Case families) with mothers of 72 families having age and neighbourhood matched non diarrhoeal children (control families) using a logistic regression model. Five risk behaviours were identified and these are bottle feeding (OR-2.87; CI-1.30 to 6.34), non-use of soap for cleaning feeding container (OR-2.61; CI-1.30 to 5.23), water storage in wide-mouthed container (OR-2.75; CI-1.27 to 5.96), use of pond water for the same (OR-2.36; CI-1.15 to 4.84) and indiscriminate disposal of children's stool (OR-1.99; CI-0.97 to 4.08). Around 83 per cent of diarrhoeal families could be predicted using these five variables only. The first three of these five risk behaviours were responsible for occurrence of significantly higher incidence (3 or more episodes) of diarrhoea in the case families. All these risk behaviours are amenable to change if suitable intervention is initiated. The result of this study would be helpful in reducing diarrhoea associated morbidity to a substantial level.

Case-Control Studies↗

Isolation of Escherichia coli to detect faecal contamination of infants and their mothers in West Bengal.

The present study was undertaken to gain insight into the sources of faecal contamination of infants in rural Bengal. It was carried out in three villages near Calcutta, India, from June 1993 to August 1995 among 148 infants and their mothers. Escherichia coli was used as an indicator of faecal pollution. A total of 725 samples, including hand rinsings of children and mothers, feeding utensils and leftover food were examined. The total isolation rate of faecal E. coli was 30%. The isolation rates from hands of children and mothers were 17% and 40% respectively. The germs from 30% of utensils and 59% of leftover food and drinks were recovered further. The study highlights the precarious hygiene in rural Bengal.

Adult↗

Effects of low concentrations of okadaic acid in HeLa cells.

HeLa cells treated for prolonged period with okadaic acid (OA; 5-10nM) inhibiting protein phosphatase 2A (PP2A) and also protein phosphatase 1 (PP1) partially showed prolonged effects on mitotic progression. In the presence of OA cells progressed normally in mitosis almost upto 4 hr, then a progressive accumulation of mitotic cells could be noticed. Most of the mitotic cells seemed to be arrested at the metaphase-anaphase transition point. In arrested mitotic cells the chromosomes remained arranged at the equiatorial plate, but with prolonged treatment the chromosomes got either scattered or clumped. However, a slow release into anaphase could also be observed after 15 hr treatment. Immunofluorescence studies for microtubules and electron microscope investigations indicated the dearrangement of spindle fibres, and a prolonged treatment led to the formation of multipolarity. This was also confirmed by spread preparations of chromosomes and the formation of multinucleate cells in preparations released from the mitotic block. Chromosomes became highly condensed showing mostly nondisjunction, but separation of sister chromatids could be observed in many cells. Immunoblot assays indicated a degradation of cyclin A, but the cyclin B1 level was significantly higher in the arrested mitotic cells after 12 hr treatment. After 24 hr of treatment the cyclin B1 level was slightly lower in arrested cells. Possible roles of protein phosphatase 2A inhibition and a prolonged partial inhibition of PP1 on the mitotic progression and the cyclin degradation at the metaphase-anaphase transition have been discussed.

Enzyme Inhibitors↗

Fibrothorax--problem, profile and prevention.

Fibrothorax is a common clinical condition found in everyday clinical practice. The clinical horizon of fibrothorax can be differentiated into pleural and lung parenchymal fibrosis. The two groups can be differentiated clinically and also by investigations. A thorough understanding of the process gives one better knowledge as to their different aetiologies, presentations and prognoses. The nature of prevention of this meance varies in these types. Patient's drug compliance status is important in preventing primary lung parenchymal fibrosis whereas physician's adequate care for pleural drainage is important in the prevention of pleural fibrosis. In this prospective study, observations were made on (1) the clinical presentation of 100 cases of fibrothorax and its relation to the primary disease, (2) aetiological distribution of the cases of fibrothorax and (3) scope of prevention, if any.

Adult↗