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Biomedical subjects

D Shah

Publications and source records attributed to D Shah.

At least 37 records · Page 2Linked to original sources
PubMed2001

Cholelithiasis in a child--an unusual presentation of Wilson's disease.

A nine year old mentally retarded girl with moderate splenomegaly and ascites presented with chronic cholelithiasis. The presence of Kayser-Fleischer rings and low serum ceruloplasmin level confirmed the diagnosis of Wilson's disease. Cirrhosis of liver and recurrent episodes of hemolysis--these two common complications of Wilson's disease make an ideal setting for gall stone formation. Only three such cases have been reported worldwide and ours is the first case report from India. We suggest that cholelithiasis and splenomegaly in a child without evidence of congenital hemolytic disease should be taken as a suspect of Wilson's disease.

Child↗
PubMed2000

Differential pacing for distinguishing block from persistent conduction through an ablation line.

BACKGROUND: Because complete linear conduction block is necessary to minimize the recurrence of reentrant tachycardias such as typical atrial flutter, we investigated a simple technique to recognize a persistent gap or complete linear block. METHODS AND RESULTS: We prospectively evaluated cavotricuspid isthmus conduction in 50 patients (age 63+/-8 years, 43 men) after radiofrequency ablation. The distal and proximal bipoles of a quadripolar catheter placed close to the ablation line were successively stimulated during recording from the ablation line. We hypothesized that because the initial and terminal components of local potentials reflected activation at the ipsilateral and contralateral borders of the ablation lesion, a change to a more proximal pacing site without moving the catheter would prolong the stimulus to the initial component timing, whereas the response of the terminal component would depend on the presence of block or persistent conduction. A shortening or no change in timing of the terminal component would indicate block, whereas lengthening would indicate persistent gap conduction. The results were compared with previously described criteria for isthmus block. Ninety-two sites were assessed: 17 before and 75 after the achievement of complete isthmus block. The timing of the initial component was delayed by 19+/-9 ms, and the terminal component was advanced by 13+/-8 ms after block and delayed by 12+/-9 ms in case of persisting conduction. The sensitivity, specificity, and positive and negative predictive values for linear block were 100%, 75%, 94%, and 100%, respectively. CONCLUSIONS: An accurate assessment of isthmus block or persistent isthmus conduction is possible with this technique of differential pacing.

Aged↗
PubMed2000

Dual-loop intra-atrial reentry in humans.

BACKGROUND: Dual-loop atrial reentrant tachycardias have not been clinically described. METHODS AND RESULTS: Five patients (3 men, 2 women; mean age, 48+/-16 years) were studied 24+/-15 years after surgical closure of an ostium secundum atrial septal defect for drug-resistant atrial tachycardia. Complete tachycardia mapping was performed in the right atrium with multipolar catheters and a 3-dimensional electroanatomic mapping system (Biosense), followed by linear radiofrequency ablation of the narrowest part of each complete loop. Six tachycardias with a typical flutter morphology, a cycle length of 262+/-40 ms, and a superior f-wave axis (-77+/-11 degrees ) were mapped, 4 with a Biosense map including 106+/-32 points. Five figure-8 tachycardias had a counterclockwise loop around the tricuspid valve sharing a common anterior channel with a clockwise loop around the lateral atriotomy scar. One tachycardia was thought to have 2 counterclockwise loops around the same obstacles. Radiofrequency delivery in the cavotricuspid isthmus in each case transformed the tachycardia without any pause in a different morphology tachycardia with an inferior P-wave axis (50+/-42 degrees ) and nearly the same cycle length (272+/-39 ms) but with the periatriotomy loop alone. This arrhythmia required ablation of a second isthmus: between the lower end of the atriotomy and the inferior vena cava in 4 and the superior tricuspid annulus in 1. After a follow-up of 19+/-6 months, there were no recurrences. CONCLUSIONS: Figure-8 double-loop tachycardias mimicking the ECG pattern of a common atrial flutter occur in some patients after a surgical atriotomy. Ablation of 1 loop produces a sudden transformation to a new reentrant tachycardia formed of the remaining loop that requires ablation at a second isthmus.

Adult↗
PubMed2000

Sequence of PHA synthase gene from two strains of Rhodospirillum rubrum and in vivo substrate specificity of four PHA synthases across two heterologous expression systems.

A 3.0-kb genomic fragment has been isolated from Rhodospirillum rubrum (ATCC 25903) that contains an open reading frame (ORF) with strong homology to other known polyhydroxyalkanoate (PHA) synthase genes. This ORF has lower homology to the R. rubrum strain Ha PHA synthase than would be expected within the same species. We have conducted a series of heterologous expression studies evaluating the in vivo substrate specificity of PHA synthase genes from Rhodobacter sphaeroides, Ralstonia eutropha (formerly Alcaligenes eutrophus), Thiocystis violacea, and Nocardia corrallina, within the PHA-synthase-negative hosts, Ralstonia eutropha DSM541 and Pseudomonas putida GpP104. The N. corrallina PHA synthase incorporated the highest percentage of C5 monomers in the polymer when fermented in medium supplemented with 0.1% heptanoate as the sole carbon source. When the T. violacea and R. sphaeroides were expressed in the PHA-negative host DSM541, a greater percentage of C5 monomer was observed in the polymer as compared to the expression of the PHA synthase of R. eutropha, when the transconjugants were fermented in medium supplemented with 0.4% propionate. Evaluation for preference of medium-chain-length monomers demonstrated the flexibility of the N. corrallina, T. violacea, and R. eutropha synthase genes to polymerize a copolyester composed of short- and medium-chain-length monomers when the respective transconjugants were fermented in medium supplemented with 0.5% octanoate. These studies demonstrate that the PHA synthase from N. corrallina, T. violacea, and R. eutropha are able to polymerize a copolyester composed of short- and medium-chain-length monomers, while the PHA synthase from R. sphaeroides lacks this ability and only produces a short-chain-length polymer. These observations suggest that the composition of the PHA from the PHA-producing organisms does not necessarily reflect the inherent specificity of the PHA synthase.

Acyltransferases↗
PubMed2000

Multiple sources initiating atrial fibrillation from a single pulmonary vein identified by a circumferential catheter.

The pulmonary veins are the predominant source of ectopic activity initiating AF. The reproducibility of intrapulmonary vein activation during ectopic activity and/or initiation of multiple AF episodes was examined. Eighty-nine pulmonary veins (PVs) among 29 patients undergoing radiofrequency ablation of AF were studied with a 15- to 20-mm diameter, circumferential PV catheter equipped with ten electrodes and a deflectable shaft. Local electrograms were recorded simultaneously during sinus rhythm, ectopic activity, or AF onset, spontaneously or induced via the catheter left in a stable position. Fifty-four arrhythmogenic veins were identified, 39 showing isolated ectopy, and 8 displayed repetitive ectopy (in salvos). The earliest site of activation and the sequence of intra-PV activation during isolated ectopy was identical to that observed during consecutive ectopic complexes in 77% and variable in 23% during isolated ectopy. The earliest activity was sometimes limited to a single bipole. During repetitive ectopy and AF initiation, multiple sources and/or variable activation patterns were noted in 53% of instances, indicating the presence of multiple arrhythmogenic foci within the same PV. Simultaneous electrogram recordings with a circumferential PV catheter identified the presence of multiple arrhythmogenic foci within a single PV.

Atrial Fibrillation↗
PubMed2000

Definitive molecular evidence of renin-angiotensin system in human uterine decidual cells.

The tissue renin-angiotensin system (RAS) has been suggested to be present in human gestational tissues, but uncertainty exists about the authenticity of this RAS, and the cellular origin of this RAS has not been defined. In the present study, we confirmed the presence of authentic renin and angiotensinogen in the prolactin-producing decidual tissue by sequencing the cDNAs generated through reverse transcription-polymerase chain reaction, confirming cDNA product sizes, and by performing Northern blot analysis of the RNA. Our comparative data demonstrate that prolactin has the highest expression in the decidual tissue, followed by renin, and that angiotensinogen has the least expression. We demonstrated with fluorescent in situ hybridization that prolactin-expressing endocrine decidual cells are the same cells that express both renin and angiotensinogen. These results have implications in regard to how the decidual RAS may be regulated and what potential role this local RAS may have in the pathogenesis of preeclampsia.

Angiotensinogen↗
PubMed2000

POU genes in metazoans: homologs in sea anemones, snails, and earthworms.

Previously undescribed POU genes were detected in several invertebrate phyla using redundant primers in a polymerase chain reaction (PCR) that targeted highly conserved sequences encoding known POU-domains. A class IV gene and a gene tentatively assigned to class VI were identified in sea anemones (Condylactis), two distinct class III genes were identified in snails (Biomphalaria), and a single class IV gene was identified in earthworms (Lumbricus). The identification of POU genes in cnidarians, mollusks, and annelids completes a survey of the major metozoan phyla. As POU genes exist in all of these organisms, they appear to be a fundamental characteristic of the metazoan lineage, and may have played a major role in the diversification of these organisms.

Amino Acid Sequence↗
PubMed2000

Evaluation of the WHO/UNICEF algorithm for integrated management of childhood illness between the ages of one week to two months.

OBJECTIVE: To evaluate the utility of the WHO/UNICEF algoritham for integrated management of childhood illness (IMCI) between the ages of 1 week to 2 months. DESIGN: Prospective observational. SETTING: The Outpatient Department and Emergency Room of a medical college hospital. METHODS: 129 infants presenting to Outpatient Department (n=70) or Emergency Room (n=59) were assessed and classified as per 'IMCI' algorithm and treatment required was identified. A detailed evaluation with all relevant investigations was also done for these subjects. The final diagnoses made and therapies instituted on this basis served as 'gold standard'. The diagnostic and therapeutic agreement between 'gold standard and the 'IMCI' was computed. RESULTS: More than one illness was present in 97(75.2%) of subjects as per 'gold standard' (mean 2.1). Subjects having any referral criteria as per 'IMCI' algorithm had a greater (p=0.002) co-existence of illnesses (mean 2.3 vs. 1.8 illnesses per child, respectively. IMCI algorithm covered majority (81-84%) of the recorded diagnoses either partly (40-41%) or fully (40-44%). The referral criteria proved quite sensitive (86-87%) in predicting hospitalization but had a lower specificity (53-58%). a total agreement with IMCI was found in 60-66% cases. The mismatch (34-40%) was more commonly of overdiagnosis (21-23%) rather than underdiagnosis (15-21%). The sensitivity of the algorithm to identify serious bacterial infection was high (96.1-96.5%) while the specificity was relatively low (51. 8-59.7%). Upper respiratory infection (URI)emerged as an important cause resulting in unnecessary referrals (13 out of 21 cases). Of the 43 cases identified as diarrhea by the algorithm, 6 had breast fed stools, which do not require any therapy. The 'IMCI' algorithm had a provision for preventive services of immunization and breastfeeding counseling (18% possibility of availing missed opportunities in both). CONCLUSION: There is a sound scientific basis for adopting IMCI approach even in young infants as there is a need to improve the specificity of referral criteria. Two important conditions identified for possible refinement are URI and breast fed stools

Algorithms↗
PubMed2000

Complicated appendicitis: is there a minimum intravenous antibiotic requirement? A prospective randomized trial.

The proper duration of postoperative intravenous (IV) antibiotics in patients suffering complicated (perforated or gangrenous) appendicitis is debatable. Some advocate a set minimum number of IV antibiotic days whereas others discontinue IV antibiotics depending on the patient's clinical course regardless of the length of therapy. Our objective was to determine whether there are differences in morbidity and resource utilization between the two treatment methodologies. Ninety-four patients with intraoperative findings of complicated appendicitis were included. In all patients IV antibiotics were discontinued on the basis of clinical factors. However, Group 1 patients were given a minimum 5-day IV antibiotic course whereas Group 2 patients had no minimum IV antibiotic requirement. Group 1 patients received more IV antibiotics than Group 2 patients did (5.9 vs 4.3 days; P = 0.014). Infectious complications were not statistically different between the two groups (13.0% in Group 1 and 12.5% in Group 2). Average hospital stay was also not statistically different between the two groups. The data suggest that a protocol with no minimum IV antibiotic requirement in patients with complicated appendicitis does not increase morbidity. Furthermore, the protocol arm with no minimum IV antibiotic requirement led to less IV antibiotic use but did not significantly decrease hospital stay.

Administration, Oral↗
PubMed1999

Detection of IgM to hepatitis B core antigen in a reductant containing, chemiluminescence assay.

The Abbott PRISM(R) hepatitis B core (HBc) antigen assay is an automatic in vitro competitive chemiluminescence immunoassay for the detection of total antibody to HBc (anti-HBc) antigen in human serum or plasma. The assay utilizes cysteine solution as a reducing reagent in order to maximize specificity. To help understand the effect of cysteine on detection of anti-HBc antigen, we separated and purified anti-HBc IgM and IgG from human plasma using size exclusion, protein A/G, and affinity chromatography techniques. We showed that cysteine affected the reactivity of anti-HBc IgM with recombinant HBc (rHBc) antigen but not the reactivity of anti-HBc IgG. Anti-HBc IgM treated with cysteine yielded byproducts which were reactive in the PRISM HBcore assay. Reduction-sensitive factor (RSF) - IgM fraction from serum known to be non-specific for anti-HBc activity, similarly treated with cysteine, was no longer reactive in the PRISM HBcore assay. We showed that cysteine treatment is effective against non-specific IgM in human blood. Also, the inclusion of cysteine in the PRISM HBcore assay does not compromise the detection of HBc specific antibodies.

Antibody Specificity↗
PubMed1999

Design and in vivo analysis of potent non-thiol inhibitors of farnesyl protein transferase.

Inhibitors of farnesyl protein transferase (FPTase) based upon a pseudotripeptide template are described that comprise an imidazole group substituted with a hydrophobic substituent. (1, 5)-Disubstitution of the imidazole group is shown to be the optimal array that leads to potent and selective inhibitors of FPTase. A variety of aryl and isoprenyl substituents are shown to afford effective inhibitors, and the mechanism by which these compounds inhibit FPTase has been investigated. The biochemical behavior of these compounds suggests that they bind to FPTase at the site usually occupied by the protein substrate. In experiments in cell culture, the methyl ester prodrugs of these inhibitors are cell permeant and potently inhibit the posttranslational modification of H-Ras protein. Additionally, these molecules revert the phenotype of ras transformed cells as evidenced by their ability to slow the growth of ras transformed cell lines in soft agar. One of the inhibitors, as its methyl prodrug, was evaluated in two in vivo models of tumor growth. The compound selectively inhibited the growth of tumors derived from H-ras transformed cells, in nude mice, and caused the regression of preexisting tumors in an H-ras transgenic animal model.

3T3 Cells↗
PubMed1999

Relationship between DNA methylation and mutational patterns induced by a sequence selective minor groove methylating agent.

Me-lex, a methyl sulfonate ester appended to a neutral N-methylpyrrolecarboxamide-based dipeptide, was synthesized to preferentially generate N3-methyladenine (3-MeA) adducts which are expected to be cytotoxic rather than mutagenic DNA lesions. In the present study, the sequence specificity for DNA alkylation by Me-lex was determined in the p53 cDNA through the conversion of the adducted sites into single strand breaks and sequencing gel analysis. In order to establish the mutagenic and lethal properties of Me-lex lesions, a yeast expression vector harboring the human wild-type p53 cDNA was treated in vitro with Me-lex, and transfected into a yeast strain containing the ADE2 gene regulated by a p53-responsive promoter. The results showed that: 1) more than 99% of the lesions induced by Me-lex are 3-MeA; 2) the co-addition of distamycin quantitatively inhibited methylation at all minor groove sites; 3) Me-lex selectively methylated A's that are in, or immediately adjacent to, the lex equilibrium binding sites; 4) all but 6 of the 33 independent mutations were base pair substitutions, the majority of which (17/33; 52%) were AT-targeted; 5) AT --> TA transversions were the predominant mutations observed (13/33; 39%); 6) 13 out of 33 (39%) independent mutations involved a single lex-binding site encompassing positions A600-602 and 9 occurred at position 602 which is a real Me-lex mutation hotspot (n = 9, p < 10(-6), Poisson's normal distribution). A hypothetical model for the interpretation of mutational events at this site is proposed. The present work is the first report on mutational properties of Me-lex. Our results suggest that 3-MeA is not only a cytotoxic but also a premutagenic lesion which exerts this unexpected property in a strict sequence-dependent manner.

Adenine↗