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Biomedical subjects

D Singh

Publications and source records attributed to D Singh.

At least 19 recordsLinked to original sources
PubMed2006

A memory-based model for planning target reach postures in the presence of obstructions.

Existing posture prediction and motion simulation models generally lack the capability of simulating human obstruction avoidance during target reach. This compromises the utility of digital human models for ergonomics, as many design problems involve interactions between humans and obstructions. To address this problem, this paper presents a novel memory-based posture planning (MBPP) model, which plans reach postures that avoid obstructions. In this model, the task space is partitioned into small regions called cells. For a given human figure, each cell is linked to a memory that stores various alternative postures for reaching the cell. When a posture planning problem is given in terms of a target and an obstruction configuration, the model examines postures belonging to the relevant cell, selects collision-free ones and modifies them to exactly meet the hand target acquisition constraint. Simulation results showed that the MBPP model is capable of rapidly and robustly planning reach postures for various scenarios.

Biomechanical Phenomena↗
PubMed2006

Development of passive haemagglutination (PHA) and haemagglutination inhibition (HAI) technique for potency estimation of Cobra Antisnake Venom Serum (ASVS).

Antibodies against snake venom or antivenom potency are assayed quantitatively by in-vivo neutralization test in mice, which requires large number of laboratory animals. In potency assays of biological substances such as antivenoms, it is highly desirable to avoid suffering and death of animals by substituting in-vivo method with in-vitro methods, provided such methods measure life-saving capability with precision similar to that of in-vivo method. The in-vitro tests determine the neutralizing power of antivenom by permitting the evaluation of a particular biological activity of the venom and its neutralization after mixing the venom with the antivenom [Theakston RDG, Reid HA. Development of simple standard assay procedures for the characterization of snake venom. Bull WHO 1983;61:949-956; Gutierrez JM, Rojas G, Lomonte B, Gene JA, Chaves F, Alvarado J, et al. Standardizing of assays for testing the neutralizing ability of antivenoms. Toxicon 1990;28:1127-1129; Theakston R.D.G. Comments on letter of Gutierrez et al. on standardization of assays for testing the neutralizing ability of antivenoms. Toxicon 1990;28:1131-1132; Harvey AL, Barfaraz A, Thomson E, Faiz A, Preston S, Harris JB. Screening of snake venom for neurotoxic and myotoxic effects using simple in-vitro preparation from rodents and chicks. Toxicon 1994;32:257-265; World Health Organization Progress in characterization of venom and standardization of anti-venoms. Geneva: WHO offset publication; 1981. p. 58.]. Hence, the ideal requirements for an assay in detecting venom and venom antibody include high level of sensitivity, specificity (ability to differentiate between venom and venom antibody produced by closely related species of snakes), reproducibility and simplicity. A new in-vitro procedure for quantitative analysis of potency of ASVS by passive haemagglutination (PHA) and haemagglutination inhibition (HAI) has been explored. The methods described are simple, rapid, economical, reproducible and useful in replacing the more expensive in-vivo neutralization assays. Moreover, it also eliminates the use of laboratory animals.

Animals↗
PubMed2006

A phase II clinical and pharmacodynamic study of temsirolimus in advanced neuroendocrine carcinomas.

Standard cytotoxic treatments for neuroendocrine tumours have been associated with limited activity and remarkable toxicity. A phase II study was designed to evaluate the efficacy, safety and pharmacodynamics of temsirolimus in patients with advanced neuroendocrine carcinoma (NEC). Thirty-seven patients with advanced progressive NEC received intravenous weekly doses of 25 mg of temsirolimus. Patients were evaluated for tumour response, time to progression (TTP), overall survival (OS) and adverse events (AE). Twenty-two archival specimens, as well as 13 paired tumour biopsies obtained pretreatment and after 2 weeks of temsirolimus were assessed for potential predictive and correlative markers. The intent-to-treat response rate was 5.6% (95% CI 0.6-18.7%), median TTP 6 months and 1-year OS rate 71.5%. The most frequent drug-related AE of all grades as percentage of patients were: fatigue (78%), hyperglycaemia (69%) and rash/desquamation (64%). Temsirolimus effectively inhibited the phosphorylation of S6 (P=0.02). Higher baseline levels of pmTOR (phosphorylated mammalian target of rapamycin) (P=0.01) predicted for a better response. Increases in pAKT (P=0.041) and decreases in pmTOR (P=0.048) after treatment were associated with an increased TTP. Temsirolimus appears to have little activity and does not warrant further single-agent evaluation in advanced NEC. Pharmacodynamic analysis revealed effective mTOR pathway downregulation.

Adult↗
PubMed2006

Self-joining of zirconia/hydroxyapatite composites using plastic deformation process.

A plastic deformation process was demonstrated to self-join 3 mol.% yttria partially stabilized zirconia (3Y-TZP)/hydroxyapatite (HA) composites. The 3Y-TZP/40 vol.% HA composites were fabricated by conventional ceramic processing by cold pressing premixed 3Y-TZP and HA powders into pellets. Densification ( approximately 90%) of composites was achieved by sintering composite powder compacts at 1450 degrees C for 5h. Optimum self-joining of 3Y-TZP/40 vol.% HA composites was obtained at 1300 degrees C for a strain rate of 5 x 10(-5)/s. The flow stress during joining was 40 MPa. Microstructural and mechanical characterizations of the joint interface demonstrated that there were no discernible differences between the joint and the composite material away from the interface.

Biocompatible Materials↗
PubMed2006

A new in-vitro agglutination technique for potency estimation of antisnake venom serum (ASVS).

Traditionally the potency of ASVS is assayed quantitatively by in-vivo neutralization test for lethality in mice. A sensitive and simple in-vitro agglutination assay for the quantitative determination of Antisnake Venom Serum (ASVS) potency is reported. The method is rapid, cheap, simple, economical and above all does not require the use of experimental animals for potency assay of in process, unpurified and purified sera batches. Among in-vitro procedures, agglutination assay was favored in comparison to flocculation as the later was found to give variable results and also time consuming (high Kf value). Before application, the method was standardized and validated for choice and concentration of particulate material (latex vs. bentonite), temperature and optimum antiserum concentration. It is well known fact that venoms lose toxicity on dilution however this study demonstrated that the bentonite adsorbed venoms of the entire four snake species viz., Cobra, Krait, Russell's viper and Echis are stable even up to 30 days of storage. Among five lots each of unpurified serum, unprocessed plasma and purified sera tested, the results were found comparable with universally accepted in-vivo biological assay. The coefficient of correlation was found to be near 1.0 within 95% fiducial limits of acceptance and also significantly less variation was observed in the mean potency values and standard deviations. For all results p value was observed to be <0.01. Results indicate that in-vitro agglutination assay is suitable and can be used for potency estimation of in process as well as unpurified and purified ASVS batches.

Adsorption↗
PubMed2006

Detection of benzimidazole resistance in Haemonchus contortus using RFLP-PCR technique.

Benzimidazole (BZ) resistance in Haemonchus contortus is linked primarily with the mutation in the beta-tubulin isotype 1 gene that substitute phenylalanine (Phe) to tyrosine (Tyr) at 200 codon of the gene. In the present study, a new restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique has been developed for detection of BZ resistance in the beta-tubulin isotype 1 gene of H. contortus. The technique utilizes two primers viz. AvikaF and AvikaR to amplify the region containing mutation in the beta-tubulin gene followed by restriction digestion. After digestion, the 'rr' individuals (homozygous resistant) revealed 257 and 48 bp bands, the 'rS' individuals (heterozygous) showed 305, 257 and 48 bp bands, while 'SS' individuals (homozygous susceptible) revealed uncut 305 bp band. A total of 162 adult male H. contortus collected from Avikanagar, Jaipur and Bikaner regions (54 from each region) were genotyped for analyzing BZ resistance in the beta-tubulin gene. Out of which, 130 adults were 'rr' types, 20 'rS' types and 12 'SS' types. The results showed that genotypic frequencies of different genotypes (rr, rS and SS) were highly significant difference among the three regions (P<0.001). The 'rr' individuals were higher (98%) in Jaipur followed by Avikanagar (93%) and Bikaner (50%) regions. Overall, the prevalence of BZ resistant allele (r) was higher (86%) as compared to BZ susceptible allele (S) (14%). The technique was also found suitable for genotyping of larvae of H. contortus and yielded reproducible results. The study indicated that RFLP-PCR is an easy, reproducible and less expensive than allele specific PCR. This technique will be helpful in establishing the prevalence rate of BZ resistance in H. contortus and can also be utilized for existing worm control programme.

Amino Acid Substitution↗
PubMed2006

Phosphorylation of neurofibromin by PKC is a possible molecular switch in EGF receptor signaling in neural cells.

Children with neurofibromatosis (NF1) typically develop central nervous system (CNS) abnormalities, including aberrant proliferation of astrocytes and formation of benign astrocytomas. The NF1 gene encodes neurofibromin, a Ras-GAP, highly expressed in developing neural cells; the mechanism of regulation of neurofibromin as a Ras-GAP, remains however unknown. We now show that, in response to EGF, neurofibromin is in vivo phosphorylated on serine residues by PKC-alpha, in human, rat, and avian CNS cells and cell lines. EGF-induced PKC phosphorylation was prominent in the cysteine/serine-rich domain (CSRD) of neurofibromin, which lies in the N-terminus and upstream of the Ras-GAP domain (GRD), and this modification significantly increased the association of neurofibromin with actin in co-immunoprecipitations. In addition, we show that Ras activation in response to EGF was significantly lowered when C62B cells overexpressed a construct encoding both CSRD + GRD. Moreover, when PKC-alpha was downregulated, the Ras-GAP activity of CSRD + GRD was significantly diminished, whereas overexpressed GRD alone acted as a weaker GAP and in a PKC-independent manner. Most importantly, functional Ras inhibition and EGF signaling shifts were established at the single cell level in C6-derived cell lines stably overexpressing CSRD + GRD, when transient co-overexpression of Ras and PKC-depletion prior to stimulation with EGF-induced mitosis. Taken together, these data provide the first evidence of a functional, allosteric regulation of GRD by CSRD, which requires neurofibromin phosphorylation by PKC and association with the actin cytoskeleton. Our data may suggest a novel mechanism for regulating biological responses to EGF and provide a new aspect for the understanding of the aberrant proliferation seen in the CNS of children with NF1.

Animals↗
PubMed2006

Floating thrombus in the brachio-cephalic trunk.

Floating thrombus in a non-aneurysmal and non-atherosclerotic brachio-cephalic trunk is an extremely rare event with potentially catastrophic complications. There is a risk of both peripheral and cerebral embolization. We present a very rare case of floating thrombus in the brachio-cephalic trunk that presented with advanced ischaemia of the right upper limb. Confirmation of the diagnosis was done by CT angiogram. The upper limb symptoms were relieved by thrombectomy, supported by anticoagulation. For floating thrombus in the brachiocephalic trunk, the patient was started on aggressive anticoagulation therapy and there was significant resolution after two weeks and complete resolution after one month.

Adult↗
PubMed2006

Plethysmography and impulse oscillometry assessment of tiotropium and ipratropium bromide; a randomized, double-blind, placebo-controlled, cross-over study in healthy subjects.

AIMS: Spirometry, plethysmography and impulse oscillometry (IOS) measure different aspects of lung function. These methods have not been compared for their ability to assess long- and short-acting anticholinergic agents. We therefore performed a double-blind, placebo-controlled, four-way cross-over study in 30 healthy subjects. METHODS: Single doses of tiotropium bromide (Tio) 54 and 18 mcg, ipratropium bromide (IB) 40 mcg and placebo were administered. Specific conductance (sGaw), total lung capacity (TLC), inspiratory capacity (IC) and residual volume (RV) were measured using plethysmography, while IOS measured resistance (R5-25) and reactance (RF and X5). Pulmonary function was measured for 26 h post dose. RESULTS: Tio caused significant improvements in sGaw, forced expiratory voume in 1 s (FEV(1)), maximum mid-expiratory flow (MMEF) and R5-R25 at time points up to 26 h, with no clear differences between doses. IB improved the same parameters, but only up to 8 h. The weighted mean change (0-24 h) caused by Tio 54 mcg compared with placebo for FEV(1) was 240 ml (95% confidence interval 180, 300), while for sGaw the ratio of geometric means (Tio compared with placebo) was 1.35 (1.28, 1.41). Neither drug caused consistent statistically significant changes in RF, forced vital capacity, TLC or IC over 26 h. RV was significantly improved from 8 to 24 h by Tio 54 mcg only. CONCLUSIONS: In addition to spirometry, IOS resistance measurements and sGaw can distinguish between the effects of long- and shortacting anticholinergic effects in healthy subjects.

Adult↗
PubMed2005

Ceramide regulation of the tumor suppressor phosphatase PTEN in rafts isolated from neurotumor cell lines.

The neutral sphingolipid ceramide has been implicated in the apoptotic death of cells by a number of different mechanisms, including activation of protein kinase B (Akt) phosphatase. Here we present evidence that ceramide recruits the tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10) into membrane microdomains (rafts), where it could act to reduce the levels of polyphosphoinositides necessary for the activation of Akt. A PTEN construct with a red-fluorescent protein (RFP) tag was overexpressed in both a human cell line derived from oligodendroglioma (HOG) and a rat pheochromocytoma cell line (PC12) by means of an inducible promoter system (Tet-Off). Induction of PTEN by removal of doxycycline enhanced both capsase-3 and cell death with staurosporine, wortmannin, or C2-ceramide, whereas antisense PTEN had the reverse effect. Overexpression of PTEN also increased acid sphingomyelinase (ASMase) activity. PTEN normally has a generalized (cytosolic/membrane) distribution, but treatment with C2-ceramide translocated a fraction of the PTEN to the plasma membrane, showing a plasma membrane distribution similar to that observed for a prenylated green-fluorescent (GFP) construct. PTEN was then shown to translocate to the detergent-resistant membrane microdomain fraction (raft) of the plasma membrane. The colocalization of sphingomyelinases, ceramide, polyphosphoinositides, and PTEN in the raft fraction further suggests that the association of these lipids is critical for regulating cell death.

Androstadienes↗
PubMed2005

CT guided diagnostic foot injections.

AIM: To describe a CT technique for guiding diagnostic and therapeutic injections in the hind- and mid-foot. MATERIALS AND METHODS: Over a period of 50 months, 28 individuals were referred for diagnostic and therapeutic hind- and mid-foot injections before possible arthrodesis. A CT technique was developed that allowed entry into the various joints using a vertical approach. Numbers of joints injected were as follows: posterior subtalar, 21; talonavicular, 4; calcaneonavicular, calcaneocuboid, navicular-cuneiform and 5th metatarsocuboid joints, 1 each. RESULTS: All injections but one were technically successful. Significant relief of symptoms was noted by 16 participants, whereas for 9 there was no improvement and for 3 a partial response was achieved. CONCLUSION: CT is a simple and safe alternative to fluoroscopy for guiding diagnostic and therapeutic foot injections, and may be the technique of choice in cases of disordered anatomy.

Adult↗
PubMed2005

Does pretransplant obesity affect the outcome in kidney transplant recipients?

UNLABELLED: The effect of obesity on renal transplant outcome remains unclear due to conflicting published studies. The purpose of this study was to assess whether obesity affects the outcome in renal transplant patients. METHODS: We retrospectively analyzed 33 obese (BMI >30; mean = 34.1 +/- 3.68; group I) and 35 nonobese (BMI < or = 30; mean = 23.6 +/- 3.18; group II) renal transplants performed at our center between March 1999 to December 2002. These two groups were well matched with respect to age, sex, donor source, hypertension, diabetes, ischemic heart disease, hyperlipidemia, native kidney disease (PCKD, 6 vs 4; diabetic, 5 vs 4; glomerulonephritis, 6 vs 7; FSGS, 2 vs 2 and IgA, 2 vs 7), HLA mismatch and immunosuppressants medications (Neoral, 21 vs 25; tacrolimus, 11 vs 10; Cellcept, 28 vs 31; Prednisone, 33 vs 35; ATG, 7 vs 8; Basiliximab, 14 vs 13 and Rapamycin, 5 vs 2, groups I and II, respectively). Follow-up was from 7 months to 4.4 years. RESULTS: Significant differences were noted in operating time, wound infection, perinephric hematoma, lymphocele, and number of hospital days. There were no significant differences between the two groups in the incidence of wound dehiscence, deep vein thrombosis, pulmonary embolism, atelectasis, urine leak, delayed graft function, acute rejection rate, and the following posttransplant variables: diabetes mellitus, myocardial infarction, hyperlipidemia, hypertension, and incisional hernia. We conclude that obesity significantly increases operating time, wound complications, and hospitalizations.

Adult↗
PubMed2005

Endoscopic third ventriculostomy in post-tubercular meningitic hydrocephalus: a preliminary report.

Hydrocephalus is a common sequel of tubercular meningitis. Endoscopic third ventriculostomy (ETV) was performed in thirty-five patients. According to the duration of illness, six patients were in the early (less than 6 weeks), nineteen were in the intermediate (6 weeks to 6 months) and ten patients were in the late phase (more than 6 months) of tubercular meningitis (TBM). Six patients were in stage I, seven patients in stage II and twenty-two patients were in stage III. The overall success rate of ETV in TBM was 77 %. Sixty percent had early and seventeen percent had delayed recovery. Obstructive hydrocephalus was present in 54.3 % and 45.7 % had communicating hydrocephalus. The radiological recovery rate was 55.6 %. The outcome with a thin to transparent floor of the third ventricle was 87 %.

Adolescent↗
PubMed2005

Measuring bronchodilation in COPD clinical trials.

AIMS: The aim of this study was to compare the variability and sensitivity of impulse oscillometry (R5, X5 and RF), plethysmography (Raw and sGaw) and spirometry (FEV1, FVC and MMEF) in order to determine the most powerful technique for assessing bronchodilation in COPD clinical trials. METHODS: Twenty-four patients with COPD had impulse oscillometry, plethysmography and spirometry measured twice 30 mins apart, to determine variability. Then ascending doses of salbutamol (20, 50, 100, 200, 400 and 800 microg) were given and the same measurements made after each dose. Significant changes greater than variability were determined for each performed measurement (expressed as mean percentage improvement with 95% CI). RESULTS: Significant effects (P < 0.05) were detected after 20 microg by X5 (18.5% CI 9.8-27.2) RF (11.1% CI 7.2-15.0) and sGaw (21.5% CI 10.1-32.9), and after 50 microg by R5 (16.7% CI 10.8-22.5) and Raw (19.7% CI 13.0-26.4). FEV1 was less sensitive, detecting significant bronchodilation at 100 microg (10.2% CI 7.4-12.9). CONCLUSIONS: We conclude that impulse oscillometry and plethysmography should be considered the preferred techniques for measuring bronchodilation in COPD clinical trials.

Albuterol↗