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Biomedical subjects

S Dhillon

Publications and source records attributed to S Dhillon.

At least 19 recordsLinked to original sources
PubMed2007

The attitudes and beliefs of healthcare professionals on the causes and reporting of medication errors in a UK Intensive care unit.

Our aim was to explore the attitudes and beliefs of healthcare professionals relating to the causes and reporting of medication errors in a UK intensive care unit. Medication errors were identified by the unit pharmacist and semi-structured qualitative interviews conducted with 13 members of staff involved with 12 errors. Interviews were analysed using a model of human error theory. Staff identified many contributing factors, including poor communication and frequent interruptions. Organisational factors included lack of clarity on the responsibility of the second nurse's check for medication administration, lack of feedback on medication errors, and a common and accepted practice of administering medication without a complete medication order. Barriers to reporting included administrative paperwork and lack of encouragement by management. Greater feedback on medication errors seems essential to improve current practice and increase reporting.

Attitude of Health Personnel↗
PubMed2006

Efficacy of repeated high-dose hepatitis B vaccine (80 microg) in patients with chronic liver disease.

Patients with chronic liver disease (CLD) respond poorly to standard hepatitis B (HBV) vaccine given as sequential 20 microg IM shots because of an overall impaired immune response. Many of these patients go on to liver transplantation and are at risk of acquiring recurrent or de novo HBV infection. To evaluate the efficacy and safety of high-dose (80 microg) IM HBV vaccination in patients with CLD who had previously failed to respond to a standard three-dose schedule of 40 microg IM vaccine given monthly. A retrospective review was undertaken at our institution of 79 patients with CLD who were treated with high-dose (80 microg) HBV vaccinations. All had previously failed a three-dose course of 40 microg HBV vaccine. An HBV vaccine response was defined as an anti-HBs titer greater than 100 mIU/ml. Liver enzymes, creatinine, age, prothrombin time, total vaccine dose, and MELD score were recorded. No adverse events were reported. Seventy-two per cent (57/79) of the subjects had an adequate response after receiving a mean total dose of 220 mug vaccine (range 80-800 microg). Twenty-eight per cent (22/79) of the subjects did not respond after receiving a mean total dose of 420 microg vaccine (range 240-720 microg). Non-responders had more severe hepatic disease defined as a higher mean total bilirubin level (p = 0.003) and a lower mean albumin level (p < 0.05). Age, prothrombin time, MELD score, and creatinine were not statistically significant between the responders and non-responders. Repeated high-dose (80 microg) HBV vaccination, in patients who do not respond to standard HBV vaccine doses, is safe and effective in the majority of patients with CLD.

Adult↗
PubMed2004

The in vitro antibacterial/synergistic activities of Withania somnifera extracts.

The methanol, hexane and diethyl ether extracts from both leaves and roots of Withania somnifera were evaluated for the antibacterial/synergistic activity by agar plate disc-diffusion assay against Salmonella typhimurium and Escherichia coli. Different concentrations of Tibrim, a combination of rifampicin and isoniazid, were tested to find out the minimum inhibitory concentration (MIC), which came out to be 0.1 mg/ml for S. typhimurium and E. coli. From the six extracts tested, only methanol and hexane extracts of both leaves and roots were found to have potent antibacterial activity. A synergistic increase in the antibacterial effect of Tibrim was noticed when MIC of Tibrim was supplemented with these extracts.

Anti-Bacterial Agents↗
PubMed2004

Therapeutic impact of abdominopelvic computed tomography in patients with acute abdominal symptoms.

PURPOSE: To determine the diagnostic and therapeutic impact of abdominopelvic computed tomography (CT) in patients with acute abdominopelvic pain. MATERIAL AND METHODS: Referring clinicians completed pre-CT and post-CT questionnaires for 50 patients in whom CT had been requested because of acute abdominopelvic pain. Clinicians recorded their leading diagnosis, confidence in this, and intended management. Following CT, clinicians again recorded these responses in the light of CT findings. Responses pre-CT and post-CT were compared in order to determine diagnostic and therapeutic impact. RESULTS: Diagnostic confidence rose significantly following CT (mean score 6.8 pre-CT versus 8.3 post-CT; P<0.0001). Intended management changed because of CT findings in 29 (58%) patients: 14 (28%) subjects whose intended management was surgical were treated medically and an additional 2 were transferred to gynecological care; 4 patients whose intended management was medical were treated surgically; 2 patients whose intended management was medical were treated by percutaneous drainage; a patient whose intended management was percutaneous drainage was treated by surgery. Of 6 patients with uncertain management pre-CT, 2 were treated surgically and 4 medically. The leading diagnosis also changed as a consequence of CT in 7 (33%) of 21 patients in whom intended management did not alter. CONCLUSION: CT in patients with acute abdominopelvic pain has considerable diagnostic and therapeutic impact, altering management in 58% of patients studied. The major effect is to avert intended laparotomy.

Abdomen, Acute↗
PubMed2003

Epistatic interaction between variations in the angiotensin I converting enzyme and angiotensin II type 1 receptor genes in relation to extent of coronary atherosclerosis.

OBJECTIVE: To test the hypothesis that gene-gene interaction of the renin-angiotensin system is associated with an effect on the extent of coronary atherosclerosis. SETTING AND RESULTS: A cohort of 1162 patients with coronary artery disease were genotyped for genetic polymorphisms in the renin-angiotensin system. Patients carrying the D allele of the angiotensin I converting enzyme (ACE) gene had greater coronary extent scores (defined as the number of coronary segments with 5% to 75% stenosis) than those not carrying this allele (p = 0.006 in non-parametric analysis and p = 0.019 in parametric analysis). This association remained significant after adjusting for age, body mass index, hypertension, and diabetes, which were also significantly associated with coronary extent scores. There was a significant interaction (p = 0.033) between genotypes of ACE and angiotensin II type 1 receptor (AGTR1). The association between the ACE gene D allele and increased coronary extent scores was significant (p = 0.008 in non-parametric and p = 0.027 in parametric analysis) in those carrying the +1166 C allele of the AGTR1 gene, but was absent in those not carrying the AGTR1 gene +1166 C allele. CONCLUSION: These findings suggest that variation in the ACE and AGTR1 genes and their interaction may not only contribute to susceptibility of coronary artery disease as previously found but also modify the disease process, thus contributing to interindividual differences in severity of the disease.

Cohort Studies↗
PubMed2002

The therapeutic impact of abdominal ultrasound in patients with acute abdominal symptoms.

AIM: The technical performance of abdominal ultrasound in the investigation of acute abdominal pain has been thoroughly investigated but its therapeutic effects are less well understood. We aimed to determine the therapeutic effect of abdominal ultrasound in the investigation of acute abdominal pain. MATERIAL AND METHODS: A pre- and post-intervention observational study design was used to determine the diagnostic and therapeutic effects of abdominal ultrasound for acute abdominal pain. Referring clinicians completed a pre-ultrasound questionnaire that detailed their leading diagnosis, confidence in this and intended management in 100 consecutive adult patients. Following ultrasound a second questionnaire was completed. This again detailed the leading diagnosis, confidence in this and their intended management. Clinicians quantified the management contribution of ultrasound both for the individual case in question and in their clinical experience generally. RESULTS: The leading diagnosis was either confirmed or rejected in 72 patients and a new diagnosis provided where no prior differential diagnosis existed in 10. Diagnostic confidence increased significantly following ultrasound (mean score 6.5 pre-ultrasound vs 7.6 post-ultrasound, P < 0.001). Intended management changed following ultrasound in 22 patients; 15 intended laparotomies were halted and a further seven patients underwent surgery where this was not originally intended. Ultrasound was rated either 'very' or 'moderately' helpful in 87% of patients, with 99% of clinicians finding it either 'very' or 'moderately' helpful generally. CONCLUSION: Abdominal ultrasound has considerable diagnostic and therapeutic effect in the setting of acute abdominal pain.

Abdomen, Acute↗
PubMed2002

Evaluation of valaciclovir dosage reduction in continuous ambulatory peritoneal dialysis patients.

In continuous ambulatory peritoneal dialysis (CAPD) patients, acyclovir-induced neurotoxicity is reported to be associated with high serum drug levels even when following the recommended reduced doses for this renal failure population. In view of the high oral bioavailability of valaciclovir (the L-valyl ester of acyclovir) the risk of neurotoxicity becomes more prominent. The present study was conducted in 12 CAPD patients who were administered a single oral dose of 500 mg valaciclovir. Acyclovir was analyzed by high-performance liquid chromatography. Relative pharmacokinetic parameters were estimated based on acyclovir concentrations at 8, 12 and 24 h post-dose. High inter-patient variations were observed with acyclovir apparent total clearance 7.238 +/- 4 l/h and half-life (T1/2) 22.27 +/- 16.82 h. However, dosage simulations confirmed supratherapeutic acyclovir concentrations for all participants when following the recommended dose of 1,000 mg valaciclovir/24 h for varicella zoster infections.

Acyclovir↗
PubMed2002

Nurses' confidence and pharmacological knowledge: a study.

The introduction of nurse prescribing will assist the government to deliver its agenda of providing patients with faster access to advice and health services. This study evaluated the knowledge base, self-rated knowledge and confidence, for a prescribing role, in a group of community nurses in Essex. A questionnaire was distributed to 183 community nurses recruited using a random, stratified method, and 110 nurses returned completed forms. Nurse prescribers in the sample were more confident and rated their knowledge more highly when compared with non-prescribing nurses. However, prescribers' actual medication-related knowledge, relative to their high levels of confidence, was not confirmed with performance on case scenarios. In responses to the case scenarios, prescribers did not perform as well as non-prescribers on all five analysed scenarios. The overall assessment of the nurses' response to the OTC case scenarios showed a poor performance when compared with prescription cases. There is a need to improve community nurses' levels of confidence and their abilities in coping with medication-related issues at pre-registration and post-registration level.

Attitude of Health Personnel↗
PubMed2001

An efficient procedure for genotyping single nucleotide polymorphisms.

Analysis of single nucleotide polymorphisms (SNPs) has been and will be increasingly utilized in various genetic disciplines, particularly in studying genetic determinants of complex diseases. Such studies will be facilitated by rapid, simple, low cost and high throughput methodologies for SNP genotyping. One such method is reported here, named tetra-primer ARMS-PCR, which employs two primer pairs to amplify, respectively, the two different alleles of a SNP in a single PCR reaction. A computer program for designing primers was developed. Tetra-primer ARMS-PCR was combined with microplate array diagonal gel electrophoresis, gaining the advantage of high throughput for gel-based resolution of tetra-primer ARMS-PCR products. The technique was applied to analyse a number of SNPs and the results were completely consistent with those from an independent method, restriction fragment length polymorphism analysis.

DNA↗
PubMed2001

Invasiveness of cutaneous malignant melanoma is influenced by matrix metalloproteinase 1 gene polymorphism.

The matrix metalloproteinases (MMPs) are implicated in connective tissue destruction during cancer invasion and metastasis. A naturally occurring variant arising from the insertion or deletion of a guanine in the promoter of the MMP-1 gene has recently been reported and shown to influence its transcriptional activity in melanoma cells. In this study, MMP-1 genotype was determined in 139 Caucasian patients with cutaneous malignant melanoma. The insertion allele was associated with deep invasive, and therefore poorer-prognosis, primary tumors [(34% of patients with vertical growth phase tumor were homozygous for the insertion allele compared with 17% of patients with horizontal growth phase tumor (P = 0.0333; odds ratio = 2.51)]. These data suggest that the invasiveness of cutaneous malignant melanoma is influenced by variation in the MMP-1 gene promoter that affects MMP-1 expression.

Cell Division↗
PubMed2001

Polymorphisms in matrix metalloproteinase-1, -3, -9, and -12 genes in relation to subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Intracranial aneurysm, which underlies the vast majority of subarachnoid hemorrhage incidences, has a multifactorial etiology, and the importance of genetic factors is increasingly recognized. Development and rupture of intracranial aneurysms involve degradation and remodeling of the vascular wall matrix in which the matrix metalloproteinases (MMPs) play an important role. The possible impact of MMP gene polymorphisms on susceptibility to intracranial aneurysms is still controversial, with conflicting data from different reported studies. METHODS: In this study we analyzed 5 different functional promoter polymorphisms in the MMP-1, MMP-3, MMP-9, and MMP-12 genes in a sample of 92 patients with aneurysmal subarachnoid hemorrhage and 158 healthy control subjects, all from southern England. RESULTS: No significant difference was detected between the patient and control groups in genotype distribution of any of the polymorphisms studied. CONCLUSIONS: The data do not support the hypothesis that MMP gene variations influence the development of intracranial aneurysms in the population studied.

Adult↗
PubMed2001

Phosphatidyl-inositol-3 kinase-independent insulin action pathway(s) in the human ovary.

Hyperandrogenism observed in women with a variety of insulin-resistant states is thought to be due to a stimulatory effect of insulin on ovarian steroid hormone production. However, it is not known what mechanisms could allow the ovary to remain sensitive to insulin while classical target organs for insulin action (liver, fat, and muscle) exhibit insulin resistance. One hypothesis proposed to explain this paradox suggests that a postbinding divergence of insulin receptor signaling occurs in the ovary and that signaling pathways for steroid hormone synthesis and other ovarian effects of insulin may be distinct from classical glucose signaling pathways. We now report that activation of phosphatidyl-inositol-3 (PI-3) kinase, which is crucial for glucose transport, is not necessary for the insulin-induced stimulation of progesterone production or for the insulin-induced inhibition of insulin-like growth factor binding protein 1 (IGFBP-1) production in cultured human ovarian cells. Human granulosa cells obtained during in vitro fertilization procedures were cultured with 10, 10(2), 10(3), or 10(4) ng/mL insulin with or without preincubation with 100 nM wortmannin, a specific irreversible inhibitor of PI-3 kinase. IGFBP-1 concentration in the conditioned medium was measured using immunoradiometric assay or by Western blot analysis. Progesterone concentration was measured using RIA. Additional studies were carried out in cultures of human ovarian cells prepared from homogenized whole ovarian tissue of a woman with a family history of breast cancer and a mutation of BRCA-1 gene who underwent bilateral oophorectomy. These cells were cultured with 10(3) ng/mL insulin with or without preincubation with 100 nM wortmannin. Two-way ANOVA was used to compare mean values of IGFBP-1 and progesterone according to insulin dose and the use of wortmannin. In cultured granulosa cell medium, progesterone production was stimulated by insulin in a dose-related manner up to 175% of control (P < 0.0001). In tissue culture medium from ovarian cells obtained from a patient with BRCA-gene mutation, concentration of progesterone in the tissue culture medium increased from 2.5 +/- 0.2 ng/mL for control to 5.4 +/- 0.3 ng/mL for cells incubated with insulin (P < 0.001). IGFBP-1 production in tissue culture medium from human granulosa cells was inhibited by insulin to the nadir of 45% of control (P < 0.0001). Preincubation with wortmannin, despite complete inhibition of PI-3 kinase in both cell systems confirmed by Western blot analysis, failed to significantly alter these results. We conclude that inhibition of PI-3 kinase by wortmannin fails to abolish stimulatory effect of insulin on progesterone production or inhibitory effect of insulin on IGFBP-1 production in cultured human ovarian cells. These findings suggest that activation of PI-3 kinase, an enzyme crucial for insulin-stimulated glucose transport, is not necessary for the above effects of insulin in the ovary. These data provide evidence for the presence of PI-3 kinase-independent insulin signaling pathway(s) in human ovarian cells.

Androstadienes↗
PubMed2000

MK801 increases retinotectal arbor size in developing zebrafish without affecting kinetics of branch elimination and addition.

Visual activity refines the retinotopic map formed on tectum during regeneration and development in goldfish through an N-methyl-D-aspartate (NMDA) receptor-mediated mechanism. Retinal arbors are enlarged in fish with unrefined maps. Here, we examined the effect of NMDA receptor blockers on the development of retinotectal arbors in zebrafish. Since visual behaviors begin 68-79 h postfertilization, we blocked NMDA receptors by immersion of larvae in MK801, AP5, or CPP starting at either 48 or 72 h. We then labeled axons with DiI at 72 or 96 h and examined them 5-9 h later. Arbors at 101-105 h (31 cases) were larger than at 77-79 h (11 cases): The average number of branches increased from 4.0 to 7.6 and the area (convex polygon method) increased by 42%. Blocking NMDA receptors with MK801 from 72 to 101-105 h significantly enlarged arbor size, but the number of branches remained roughly the same. The length and area of the arbors were both significantly increased (21% and 36%), whereas the width increased by a smaller amount (6%). This increase was reflected in longer distances between branches within the arbor (interbranch segments, +13%) as well as in the summed length of all branches (+28%). This selective effect on the extent but not number of branches is in agreement with our previous report of strobe effects in both developing and regenerating projections in goldfish, and supports the role of NMDA receptors in the first 24 h of synaptic transmission. We also used DiO to label arbors in time-lapse images taken at hourly intervals from 77 to 112 h. These sequences confirmed that individual arbors grew during this time, but showed that rates of branch addition and deletion and branch lifetimes were unaltered by the MK801 treatment. This is consistent with a simple model of random insertion of new branches and selective activity-driven elimination of those at the periphery to keep the normal arbor focused. Blocking NMDA receptors is postulated to randomize the elimination allowing the periphery to expand, thus accounting for the enlarged areas, without change in branch numbers or branch dynamics.

2-Amino-5-phosphonovalerate↗
PubMed2000

Prospective assessment of accuracy of endoanal MR imaging and endosonography in patients with fecal incontinence.

OBJECTIVE: Endoanal MR imaging was prospectively compared with anal endosonography to determine any superiority in the characterization of sphincter morphology in fecal incontinence. SUBJECTS AND METHODS: Fifty-two consecutive patients with fecal incontinence were examined with anal endosonography and endoanal MR imaging after a detailed bowel history, clinical examination, and complete anorectal physiologic testing. External and internal anal sphincter integrity was noted on both endosonograms and MR images by two radiologists in consensus, who read individual scans in a random order to avoid recall bias. Imaging findings were subsequently compared, and arbitration of any disagreement between endosonography and MR imaging was made in consensus by a surgeon and a gastroenterologist who also had access to the patient's history, clinical examination, and anorectal physiologic testing results. RESULTS: Complete agreement was found between anal endosonographic and MR imaging interpretations in 32 patients (62%): 10 with combined external and internal sphincter injuries, two with isolated internal sphincter injury, and 20 with intact sphincters. Of 20 patients in whom results of the scans were disparate, incorrect interpretation was found on endosonography in six patients, on MR imaging in 15. Overall, one error relating to the internal sphincter was made on endosonography versus 12 on MR imaging (p = 0.002), and five errors relating to the external sphincter were made on endosonography versus six on MR imaging (p = 1.0). CONCLUSION: This study suggests that endoanal sonography and endoanal MR imaging are equivalent in diagnosing external anal sphincter injury, but MR imaging is inferior in diagnosing internal anal sphincter injury.

Adolescent↗
PubMed1999

Upregulation of KIR expression on murine bone marrow cells by paraformaldehyde fixed tumor cells.

We have previously shown that the activation of mouse spleen NK cells by IL2 is markedly boosted if paraformaldehyde fixed tumor target cells are added during the activation phase. In the present study, we have shown that such a boosting effect is not seen if mouse bone marrow (BM) cells are used instead of spleen cells. Addition of fixed tumor cells (1:100 ratio of tumor cells to BM cells) however resulted in a marked increase in the expression of Ly49 molecules on BM cells. The enhancement of Ly49 expression was not seen if fixed allogeneic BM cells were added, suggesting that Ly49 upregulation was tumor specific. Expression of Ly49A as well as Ly49C isotypes were augmented by fixed tumor cells. Moreover, increased Ly49 expression was seen on cell populations expressing TCRbeta as well as NK1.1 markers. These results indicate that exposure to tumor cells may be an important factor regulating KIR expression on NK and T cells. Implications of these results are discussed.

Animals↗