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Biomedical subjects

J Singh

Publications and source records attributed to J Singh.

At least 55 records · Page 3Linked to original sources
PubMed2004

Modular phakoemulsification training adapted for a left-handed trainee.

BACKGROUND: The increasing demand for high-volume, high-quality cataract surgery creates additional challenges for surgeons providing phakoemulsification training. We describe the modular training programme used by the Worcester Eye Department for inexperienced trainees and the adaptation of this programme to the needs of a left-handed trainee. METHODS: The intraoperative complications of a left-handed trainees' first 161 cases are reported. RESULTS: In this series, there was one case of vitreous loss (0.62%) and one case of posterior capsular tear (0.62%). Two cases developed stable anterior capsular tears (1.24%) and two cases required a single suture to ensure wound stability. CONCLUSION: We demonstrate a safe, effective and flexible method of phakoemulsification training.

Clinical Competence↗
PubMed2004

Emerging experimental therapeutics for bipolar disorder: insights from the molecular and cellular actions of current mood stabilizers.

Bipolar disorder afflicts approximately 1-3% of both men and women, and is coincident with major economic, societal, medical, and interpersonal consequences. Current mediations used for its treatment are associated with variable rates of efficacy and often intolerable side effects. While preclinical and clinical knowledge in the neurosciences has expanded at a tremendous rate, recent years have seen no major breakthroughs in the development of novel types of treatment for bipolar disorder. We review here approaches to develop novel treatments specifically for bipolar disorder. Deliberate (ie not by serendipity) treatments may come from one of two general mechanisms: (1) Understanding the mechanism of action of current medications and thereafter designing novel drugs that mimics these mechanism(s); (2) Basing medication development upon the hypothetical or proven underlying pathophysiology of bipolar disorder. In this review, we focus upon the first approach. Molecular and cellular targets of current mood stabilizers include lithium inhibitable enzymes where lithium competes for a magnesium binding site (inositol monophosphatase, inositol polyphosphate 1-phosphatase, glycogen synthase kinase-3 (GSK-3), fructose 1,6-bisphosphatase, bisphosphate nucleotidase, phosphoglucomutase), valproate inhibitable enzymes (succinate semialdehyde dehydrogenase, succinate semialdehyde reductase, histone deacetylase), targets of carbamazepine (sodium channels, adenosine receptors, adenylate cyclase), and signaling pathways regulated by multiple drugs of different classes (phosphoinositol/protein kinase C, cyclic AMP, arachidonic acid, neurotrophic pathways). While the task of developing novel medications for bipolar disorder is truly daunting, we are hopeful that understanding the mechanism of action of current mood stabilizers will ultimately lead clinical trials with more specific medications and thus better treatments those who suffer from this devastating illness.

Antimanic Agents↗
PubMed2004

Emerging experimental therapeutics for bipolar disorder: clues from the molecular pathophysiology.

Bipolar affective disorder (manic-depressive illness) is a common, severe, chronic, and often life-threatening illness, associated with significant comorbidity. The recognition of the significant morbidity and mortality of patients with bipolar disorder, as well as the growing appreciation that a high percentage of patients respond poorly to existing treatments, has made the task of discovering new therapeutic agents, that are both efficacious and have few side effects increasingly more important. Most recent agents introduced into the pharmacopeia for the treatment of bipolar disorder have been anticonvulsants and atypical antipsychotics. We propose that novel treatments developed specifically for bipolar disorder will arise from (1) understanding more precisely the molecular mechanisms of treatments that are clearly efficacious or (2) developing medications based on the knowledge obtained of the underlying pathophysiology of bipolar disorder. Knowledge with regard to the underlying pathophysiology of bipolar disorder is increasing at a rapid pace, including alterations in intracellular signaling cascades as well as impairments of cellular plasticity and resilience in critical neuronal circuits. We propose that therapeutics designed to enhance cellular plasticity and resilience and that counter maladaptive stress-responsive systems may have considerable utility for the treatment of bipolar disorder. Therapeutic strategies designed to address cellular resilience and plasticity include the regulation of neurotrophic pathways, glucocorticoid signaling, phosphodiesterase activity, and glutamatergic throughput and mitochondrial function. While the task of developing novel medications for bipolar disorder is truly daunting, these and similar approaches will ultimately lead to better medications for the millions who suffer from this devastating illness.

Antimanic Agents↗
PubMed2004

An occipital lobe epileptogenic focus in a patient with West Nile encephalitis.

Although most human cases of West Nile (WN) fever are benign, approximately 1% produce severe neurological illness. Meningitis and/or encephalitis comprise 75% of hospitalized cases with seizures in 10-15%. Occipital lobe seizures, often mimicking other primary seizure types due to extra-occipital spread, is uncommon in adults and especially so from an infectious origin. A case of WN encephalitis presenting with a simple partial seizure, focal motor, resulting from an occipital epileptogenic focus is reported. The atypical epileptogenic location of the case and the observed frequency of seizures in WN encephalitis suggest that this virus is particularly irritative to cortical neuronal networks. Thus when seizures especially with atypical EEG patterns present during an acute febrile illness in the warmer months, WN encephalitis should be considered.

Aged↗
PubMed2004

No panacea for drainage after percutaneous nephrolithotomy.

BACKGROUND AND PURPOSE: The optimal postoperative drainage system for patients undergoing percutaneous nephrolithotomy (PCNL) has not yet been determined. Each of the different tubes available has theoretical advantages and disadvantages. The objective of this study was to determine if any one system of post-PCNL drainage has any significant advantage over the others. PATIENTS AND METHODS: Sixty patients were randomized to either a 24F Re-entry tube (Group 1), an 8F pigtail catheter (Group 2), or a double-J stent (Group 3) (N = 20 for all groups). The double-J stent patients also had an 18F Councill catheter as a nephrostomy tube, which was removed on the morning of postoperative day 1. The three groups were well-matched for age, stone size, operative time, and mean number of percutaneous tracts (P > 0.05 for all). Data collected included intraoperative findings, postoperative analog pain scores and narcotic usage, presence of extravasation on postoperative nephrostogram, presence of perinephric fluid on postoperative ultrasound scans, length of stay, and whether leakage from the nephrostomy site persisted more than 48 hours after tube removal. RESULTS: There were no statistically significant differences among the three groups in terms of change in hematocrit or number of patients requiring blood transfusion; in the incidence of tube blockage, extravasation, or presence of perinephritic fluid; or in complication rates, length of hospital stay, or persistent leakage after tube removal. There was a strong trend to less postoperative leakage with the 8F pigtail than the Reentry tube (P = 0.05). Postoperative analog pain scores and narcotic usage were equivalent for all three groups. Patients Groups 1 and 2 were free of all tubes sooner than patients in Group 3 (P < 0.001). CONCLUSIONS: This study did not demonstrate an overwhelming advantage of any one drainage system over the others. All three systems were equally tolerated by patients. There may be less chance of prolonged nephrostomy-site leakage with an 8F pigtail catheter.

Catheterization↗
PubMed2004

Beneficial effects of 'lamivudine pulse' therapy in HBeAg-positive patients with normal ALT*.

Currently no therapy is given to patients with chronic hepatitis B virus (HBV) infection who are HBeAg positive with normal alanine aminotransferase (ALT) levels. Steroid priming has been shown to enhance T-helper-1 (Th-1) cell response. Lamivudine may restore immunologic competence against HBV by causing a sudden decline in the level of the virus. We examined the efficacy of lamivudine pulse therapy on the seroconversion from HBeAg to anti-HBe. This was a prospective single-blinded trial including 27 patients with chronic hepatitis B, HBeAg positive with ALT < or =1.5 times upper limit of normal (ULN). Lamivudine was administered initially for 4 weeks, then stopped for 2 weeks and later restarted and continued till 3 months after seroconversion or completion of 2 years of therapy. Twenty-six patients completed the study. Lamivudine withdrawal led to a rise in ALT levels above the ULN in 11 (42.3%) patients at 6 weeks; seven of them (63.6%) lost HBeAg compared with only two of the 15 patients (13.3%), in whom ALT levels did not rise (P = 0.011). As one patient showed a relapse, a total of eight (31%) patients responded to lamivudine pulse therapy over a mean period of 17.3 +/- 4.5 months. Responders had a higher serum albumin (P < 0.05), a lower fibrosis score (P < 0.05), and a relatively high baseline serum ALT levels (P = 0.024) than the nonresponders. YMDD mutations developed in three patients and none responded. No patient developed hepatic decompensation. Hence lamivudine pulse therapy has potential in converting HBeAg-positive, 'not-treat-worthy' (ALT < 1.5 ULN) patients to treat-worthy (ALT > 1.5 ULN) in 42%, with sustained HBeAg and HBV DNA loss in 31% patients. The effects are possibly because of a combination of antiviral and immunomodulating activities of lamivudine.

Adolescent↗
PubMed2004

[Performance of the Candida mannan antigen detection in patients with fungemia].

For several years, the Platelia Candida mannan antigen enzyme immunoassay (Candida EIA) has been commercially available as a diagnostic test for invasive candidosis. We evaluated the Candida EIA with patients with proven fungemia caused by yeasts from which at least one serum sample was available. Fifty-nine patients with 121 serum samples were included in the study. Sixty-one different yeast strains were isolated from positive blood-cultures. The Candida EIA was positive (n = 35) or borderline positive (n = 8) in 43 of 59 patients with fungemia, resulting in an overall sensitivity of 73%. For the different yeast species, the following sensitivities were calculated: Candida albicans 30 of 39 (77%), Candida glabrata 7 of 11 (64%), Candida parapsilosis 1 of 3, Candida tropicalis 2 of 2, Candida kefyr 2 of 2, Candida lipolytica 0 of 1, Candida lusitaniae 1 of 1, Candida krusei 1 borderline positive of 1, Saccharomyces cerevisiae 1 of 1. In six patients the antigen levels over time were evaluable. In three cases the antigen was positive 3-4 days before the day the blood culture was drawn, in one case on the same day, and in two cases 2 and 5 days afterwards. In conclusion, the Candida EIA was suitable for the detection of fungemia due to the major facultatively pathogenic yeast species. The test was positive in about half of the patients before blood cultures became positive. In these cases, it contributed to an early diagnosis of invasive candidiasis.

Antigens, Fungal↗
PubMed2004

Integration of virtual screening into the drug discovery process.

Advances in high-throughput virtual screening using docking, predictive ADME methods and their integration with informatics and high-performance computing are reviewed. Docking approaches have led to the identification of novel active compounds. Predictive ADME methods have improved on selective test sets with broader training sets, though extensive validation is lacking.

Combinatorial Chemistry Techniques↗
PubMed2003

Diethylene glycol poisoning in Gurgaon, India, 1998.

OBJECTIVE: To discover the cause of acute renal failure in 36 children aged 2 months to 6 years who were admitted to two hospitals in Delhi between 1 April and 9 June 1998. METHODS: Data were collected from hospital records, parents and doctors of the patients, and district health officials. Further information was obtained from house visits and community surveys; blood and stool samples were collected from other ill children, healthy family members and community contacts. Samples of drinking-water and water from a tube-well were tested for coliform organisms. FINDINGS: Most of the children (26/36) were from the Gurgaon district in Haryana or had visited Gurgaon town for treatment of a minor illness. Acute renal failure developed after an episode of acute febrile illness with or without watery diarrhoea or mild respiratory symptoms for which the children had been treated with unknown medicines by private medical practitioners. On admission to hospital the children were not dehydrated. Median blood urea concentration was 150 mg/dl (range 79-311 mg/dl) and median serum creatinine concentration was 5.6 mg/dl (range 2.6-10.8 mg/dl). Kidney biopsy showed acute tubular necrosis. Thirty-three children were known to have died despite being treated with peritoneal dialysis and supportive therapy. CONCLUSION: Cough expectorant manufactured by a company in Gurgaon was found to be contaminated with diethylene glycol (17.5% v/v), but a sample of acetaminophen manufactured by the same company tested negative for contamination when gas-liquid chromatography was used. Thus, poisoning with diethylene glycol seems to be the cause of acute renal failure in these children.

Acute Kidney Injury↗
PubMed2003

Ultrasound image characteristics of ovarian follicles in relation to oocyte competence and follicular status in cattle.

Assessment of the quality of the female gamete has become paramount for in vitro procedures. There is a need to identify reliable indicators of oocyte competence and develop a simple, non-invasive method to assess competence. The aim of this study was to investigate the relationships among ultrasonographic attributes of a follicle, its stage of development and the competence of the oocyte that it contains. We tested the hypotheses that follicular echotexture characteristics are related to: (1) the phase of development of the follicle, (2) the presence of the corpus luteum (CL) and/or the dominant follicle in the ovary, and (3) developmental competence of cumulus oocyte complexes (COC) from the same ovary. Crossbred beef cows (n=143), age 4-14 years, were given a luteolytic dose of dinoprost to cause ovulation. Ultrasound-guided ablation of all follicles > or = 4mm was done 8 days later to induce new follicular wave emergence during a luteal phase. Ultrasonographic images of dominant follicles and the three largest subordinate follicles (n=402 follicles; 84 cows) were acquired on Days 2, 3, 5 or 7 of the follicular wave (Day 0: wave emergence), i.e. growing, early-static, late static, and regressing phases of subordinate follicle development, respectively. From a subset of these animals (n=33), ovaries were collected within 30 min of slaughter and COC from subordinate follicles > or = 3mm underwent in vitro maturation, fertilization and culture to the blastocyst stage.Image analysis revealed differences in echotexture between dominant and subordinate follicles among Days 2-7 of the follicular wave. Images of dominant and subordinate follicles at Day 7 of the wave displayed consistently lower grey-scale values (P<0.05) in the peripheral antrum, follicular wall and perifollicular stroma than all other days. Follicle images displayed a consistent pattern of variation in echotexture among follicular phases. Data did not support the hypothesis of a local effect of the CL or dominant follicle on follicular echotexture. Echotexture values of the perifollicular stroma were lower in ovaries that did not produce embryos compared to ovaries that produced embryos. Our results showed that the changes in follicular image attributes are consistent with changes in follicular status. The sensitivity of the technique is not yet sufficient for use in a diagnostic setting, but results provide rationale for further development of image analysis as a tool for evaluating oocyte competence in situ.

Animals↗
PubMed2003

Stimulation of spleen cells in vitro by nanospheric particles containing antigen.

Activation of cells, in primary culture, by nanospheres containing antigen has been investigated. Single cell suspensions of spleen cells from primed and nai;ve animals were cocultured with escalating quantities of soluble tetanus toxoid (TT) or TT encapsulated within nanospheres fabricated from poly(lactide-co-glycolide) (PLGA). Concomitantly, spleen cells were also cultured in the presence of 'empty' PLGA nanospheres that contained no TT. Nanospheres loaded with antigen were found to elicit increased proliferation of splenocytes from preimmunised mice in comparison to free antigen during coculture at equivalent doses of immunogen (at low and intermediate doses). Interestingly, cellular proliferation was abolished if B-cells were removed from the splenocyte cultures. Production of IFN-gamma and IL-6 was increased, for formulated as compared to free antigen, in microcultures from both nai;ve and pre-immunised animals. Secretion of IFN-gamma or IL-6 was not observed when primed or nai;ve spleen cells were stimulated with 'empty' polymeric spheres. Some unspecific cytotoxicity was detected if cells were cocultured with high concentrations of PLGA particles, although toxic effects were not seen at concentrations where maximum levels of cytokine secretion and cellular proliferation were recorded. These cell culture data indicate that, at least in this in vitro model, nanoparticulate TT is able to elicit cytokine production that is probably consistent with increased stimulation. This mechanism is likely to be distinct from non-specific effects caused by components of the delivery vehicle itself.

Animals↗
PubMed2003

Exogenous porcine viruses.

Porcine organs, cells and tissues provide a viable source of transplants in humans, though there is some concern of public health risk from adaptation of swine infectious agents in humans. Limited information is available on the public health risk of many exogenous swine viruses, and reliable and rapid diagnostic tests are available for only a few of these. The ability of several porcine viruses to cause transplacental fetal infection (parvoviruses, circoviruses, and arteriviruses), emergence or recognition of several new porcine viruses during the last two decades (porcine circovirus, arterivirus, paramyxoviruses, herpesviruses, and porcine respiratory coronavirus) and the immunosuppressed state of the transplant recipients increases the xenozoonoses risk of humans to porcine viruses through transplantation. Much of this risk can be eliminated with vigilance and sustained monitoring along with a better understanding of pathogenesis and development of better diagnostic tests. In this review we present information on selected exogenous viruses, highlighting their characteristics, pathogenesis of viral infections in swine, methods for their detection, and the potential xenozoonoses risk they present. Emphasis has been given in this review to swine influenza virus, paramyxovirus (Nipah virus, Menagle virus, LaPiedad paramyxovirus, porcine paramyxovirus), arterivirus (porcine reproductive and respiratory syndrome virus) and circovirus as either they represent new swine viruses or present the greatest risk. We have also presented information on porcine parvovirus, Japanese encephalitis virus, encephalomyocarditis virus, herpesviruses (pseudorabies virus, porcine lymphotropic herpesvirus, porcine cytomegalovirus), coronaviruses (TGEV, PRCV, HEV, PEDV) and adenovirus. The potential of swine viruses to infect humans needs to be assessed in vitro and in vivo and rapid and more reliable diagnostic methods need to be developed to assure safe supply of porcine tissues and cells for xenotransplantation.

Animals↗
PubMed2003

Prescription of adrenaline auto-injectors for potential anaphylaxis--a population survey.

OBJECTIVE: To assess the quality of training provided to parents of children prescribed adrenaline auto-injector devices, adherence to the Chief Medical Officer's recommendation regarding specialist referral, and effect of allergies on quality of life. SETTING: Middlesbrough, Redcar and Cleveland districts in North-east England. DESIGN: Postal questionnaire to parents of all children prescribed an auto-injector in the area (n = 154). RESULTS: One hundred and seven parents replied. General practitioners were the source of initial prescription for 30 children. Fifty-one children were not referred to a specialist allergy clinic. Four parents said that they had received no training in the use of the device. Dummy auto-injectors were not used to train 51 parents. Forty-six families were not given the opportunity to retrain. Eleven parents had low or very low confidence in the use of the device, and 13 parents were unsure when to use it. Quality of life was significantly affected. Sixteen children were bullied as a result of their allergy. Thirty parents felt that their child could not do something they really enjoyed as a result of the allergy, and 39 parents felt that their own lifestyle was affected. CONCLUSION: The impact of the prescription of auto-injector devices should not be underestimated. National guidelines regarding specialist referral were often not followed, and this needs to be addressed by primary care organizations. Quality of training issues needed to be addressed and this has led to re-organization of services in our district.

Anaphylaxis↗
PubMed2003

Ovarian follicular wave synchronization and pregnancy rate after fixed-time natural mating in llamas.

The study was designed to compare the efficacy of treatments intended to induce follicular wave synchronization among llamas (Experiment 1), and to determine the effect of these treatments on pregnancy rates after fixed-time natural mating (Experiment 2). In Experiment 1, llamas were treated with: (1) saline (control, n=20); (2) estradiol and progesterone (E/P, n=20); (3) LH (LH, n=20); or (4) transvaginal ultrasound-guided follicle ablation (FA, n=20). The ovarian response was monitored daily by transrectal ultrasonography. The intervals from treatment to follicular wave emergence and to the day on which the new dominant follicle reached >/=7 mm, respectively, did not differ between the LH (2.1+/-0.3 days and 5.2+/-0.5 days, respectively) and FA groups (2.3+/-0.3 days and 5.0+/-0.5 days), but both were shorter (P<0.05) and less variable (P<0.01) than in the control group (5.5+/-1.0 days and 8.4+/-2.0 days), while the E/P group (4.5+/-0.8 days and 7.7+/-0.5 days) was intermediate. In Experiment 2, llamas at unknown stages of follicular development were assigned randomly to control, E/P, and LH groups (n=30 per group). A single, fixed-time natural mating was permitted 10-12 days after treatment. Ovulation rates did not differ among groups (control, 93%; E/P, 90%; LH, 90%; P=0.99), but the pregnancy rate was higher (P<0.05) for synchronized llamas (LH and E/P groups combined, 41/54) than for non-synchronized llamas (control group, 15/28). In conclusion, LH and FA treatments were most effective for inducing follicular wave synchronization, while E/P treatment was intermediate. Synchronization treatments did not influence ovulation rate subsequent to fixed-time natural mating, but a higher pregnancy rate in synchronized than non-synchronized llamas warrants critical evaluation of the effects of follicular status on the developmental competence of the contained oocyte.

Animals↗
PubMed2003

Development of a modified vermireactor for efficient vermicomposting: a laboratory study.

Waste has become an index of growth. Utilization of waste materials for productivity purposes is important for both economic and environmental reasons. Vermicomposting is an important aspect as it converts waste to wealth. In this context, a modified vermireactor in place of the conventional vermireactor for efficient vermicomposting has been developed. In the conventional low- and high-rate vermireactors, the space for vermicomposting is reduced due to the thick layer of vermibed at the bottom of the reactor, thus a small amount of worm casts is produced. In the modified vermireactors there was only a thick moist cloth at the bottom in place of the thick vermibed which allowed a comparatively large quantity of organic waste to be vermicomposted as compared to conventional vermireactors. Laboratory studies showed that the modified vermireactor performed better than the conventional vermireactor in average vermicast produced and mg castings l(-1) (digester volume) day(-1). The study further showed that only the volume of the vermireactor was responsible for the high yield of worm casts.

Animals↗
PubMed2003

The investigation of hypocalcaemia and rickets.

Our understanding of disorders that present with hypocalcaemia has advanced rapidly in the past decade. The molecular basis of many of these disorders and conditions associated with phosphate wasting has now been established. While many children will need specialist involvement, they often will present to general paediatricians, and appropriate investigations prior to intervention will enable early diagnosis. Not all children with hypocalcaemia and low or low normal parathyroid hormone levels have isolated hypoparathyroidism, and clinicians need to be aware of the potential for misdiagnosis. Outpatient departments and paediatric wards should have a readily accessible and comprehensive list of bloods that need to be taken when a child presents with hypocalcaemia or rickets.

Calcium↗