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Biomedical subjects

S Sidhu

Publications and source records attributed to S Sidhu.

At least 19 recordsLinked to original sources
PubMed2007

Minimally invasive parathyroidectomy using the lateral focused mini-incision technique without intraoperative parathyroid hormone monitoring.

BACKGROUND: Minimally invasive parathyroidectomy (MIP) involves scan-directed removal of a single adenoma through a 2.0-cm mini-incision without intraoperative monitoring. The aim of this study was to analyse the outcomes of MIP using such a simplified technique. METHODS: The study group comprised 500 consecutive patients undergoing MIP via a lateral mini-incision from August 2000 to September 2005. Levels of parathyroid hormone (PTH) were measured after operation solely to aid informed discharge. RESULTS: Some 97.4 per cent of patients were initially cured by MIP. Eight patients remained hypercalcaemic and a further five were normocalcaemic on the day after surgery but became hypercalcaemic again within 3 months of the procedure. Eleven of these patients were cured with subsequent re-exploration. Analysis of postoperative PTH data indicated that, at best, the use of intraoperative PTH measurement during surgery would have increased the cure rate by only a further 1 per cent. Three (0.6 per cent) of 500 patients had permanent recurrent laryngeal nerve palsy after MIP. CONCLUSION: MIP performed by the lateral focused mini-incision technique, without the use of intraoperative PTH monitoring, is a safe and effective procedure that results in outcomes equal to those of bilateral neck exploration.

Adenoma↗
PubMed2006

A meta-analysis of trials comparing Cypher and Taxus stents in patients with obstructive coronary artery disease.

AIMS: Drug-eluting stents have been shown to be superior to bare metal stents in reducing restenosis rates. Recently head-to-head trials comparing sirolimus-eluting stents and paclitaxel-eluting stents have been reported. An early combined analysis of these comparative trials is needed. The present meta-analysis was carried out to compare the effects of sirolimus-eluting stents with paclitaxel-eluting stents on the restenosis rate, major adverse cardiac events and late loss of arterial lumen diameter in patients with obstructive coronary artery disease. METHODS: Electronic (Medline, Cochrane and Embase) and manual search (Index Medicus and cross references of retrieved articles) were carried out for all the relevant articles up till March 2005. Only randomized trials with adequate data for calculation of odds ratio for restenosis rates and major adverse cardiac events using the method of DerSimonian & Laird and standardized mean difference for late loss of arterial lumen diameter were included. RESULTS: Four studies were found to be eligible for inclusion in the meta-analysis. Restenosis rate and late loss of arterial lumen diameter were significantly reduced by sirolimus-eluting stents as compared with paclitaxel-eluting stents (OR 0.598, 95% CI 0.400, 0.893, pooled mean difference -0.414, 95% CI -0.492, 0.336, respectively). The incidence of major adverse cardiac events was less with sirolimus-eluting stents as compared with paclitaxel-eluting stents (OR 0.727, 95% CI 0.518-1.018) but the results were not statistically significant. CONCLUSIONS: Sirolimus-eluting stents are superior to paclitaxel-eluting stents in decreasing restenosis rate and late loss of arterial lumen diameter. However, no statistically significant difference in major adverse cardiac events was noted between the two stents.

Coronary Stenosis↗
PubMed2005

Mutation and methylation analysis of TP53 in adrenal carcinogenesis.

AIM: To investigate the role of coding region mutation and promoter hypermethylation of TP53 in adrenocortical cancer formation. METHODS: Twenty sporadic adrenocortical cancers (ACCs) and five normal adrenal tissue samples were available for analysis. Coding region mutation of TP53 in 20 ACCs was examined by polymerase chain amplification using intronic primers for exons 2-11 and direct sequencing of the product. In 10 ACCs and five normal adrenal tissue specimens, methylation of the 16 CpG sites within the TP53 promoter was examined using bisulphite methylation sequencing. RESULTS: Coding region mutation in TP53 was demonstrated in 5 of 20 ACCs. There were four mis-sense mutations and one frameshift mutation. Four of 5 patients with a TP53 mutation had metastases at diagnosis or detected soon thereafter and 3 of 4 died of disease within 12 months of surgical resection. No methylation was seen in the TP53 promoter in 10 ACC and the five normal adrenal tissues examined. CONCLUSION: Coding region mutation in TP53 occurs in 25% of ACCs with a trend toward a poorer prognosis. Promoter methylation of TP53 is not present in ACC as a mechanism for tumour suppressor gene (TSG) inactivation and, therefore, other genes in the 17p13 region are implicated in adrenal carcinogenesis.

Adrenal Gland Neoplasms↗
PubMed2004

Influence of high fat diet (butter) on pharmacokinetics of phenytoin and carbamazepine.

The study was carried out to evaluate the effect of butter on the pharmacokinetics of phenytoin and carbamazepine. In a crossover study, phenytoin 30 mg/kg and carbamazepine 56 mg/kg were given orally to New Zealand white rabbits (n = 8 for each drug). Blood samples were drawn at different time intervals from 0-24 h from the marginal ear vein after drug administration. After a washout period of 7 days, butter (5 mg/kg) was administered for 7 days to the animals. On the 8th day, butter and phenytoin or carbamazepine were administered simultaneously and the blood samples were withdrawn at the same time points. Plasma was separated and stored at -20 degrees C until assayed for phenytoin and carbamazepine by HPLC and different pharmacokinetic parameters were calculated. Butter increased the absorption of both phenytoin and carbamazepine, as there was a significant increase in the Cmax and AUC(0-alpha) of both drugs after butter administration. No significant difference in Tmax was observed. In this study, it was found that a high fat diet increases the bioavailability of phenytoin and carbamazepine in New Zealand white rabbits.

Absorption↗
PubMed2004

Transfer and stable transgene expression of a mammalian artificial chromosome into bone marrow-derived human mesenchymal stem cells.

Mammalian artificial chromosomes (ACEs) transferred to autologous adult stem cells (SCs) provide a novel strategy for the ex vivo gene therapy of a variety of clinical indications. Unlike retroviral vectors, ACEs are stably maintained, autonomous, and nonintegrating. In this report we assessed the delivery efficiency of ACEs and evaluated the subsequent differentiation potential of ACE-transfected bone marrow-derived human mesenchymal stem cells (hMSCs). For this, an ACE carrying multiple copies of the red fluorescent protein (RFP) reporter gene was transferred under optimized conditions into hMSCs using standard cationic transfection reagents. RFP expression was detectable in 11% of the cells 4-5 days post-transfection. The RFP-expressing hMSCs were enriched by high-speed flow cytometry and maintained their potential to differentiate along adipogenic or osteogenic lineages. Fluorescent in situ hybridization and fluorescent microscopy demonstrated that the ACEs were stably maintained as single chromosomes and expressed the RFP transgenes in both differentiated cultures. These findings demonstrate the potential utility of ACEs for human adult SC ex vivo gene therapy.

Adipocytes↗
PubMed2004

A comparison of observational studies and controlled trials of heparin in ulcerative colitis.

OBJECTIVES: To compare the efficacy of heparin in ulcerative colitis (UC) as demonstrated in observational studies and controlled clinical trials. INTRODUCTION: Ulcerative colitis (UC) is a chronic condition with a relapsing and remitting course. Several studies have been conducted (observational and controlled clinical trials) to test the usefulness of heparin in this condition but the results of these studies are variable. Some studies demonstrate efficacy while others do not. METHODS: We pooled the results of observational studies and clinical trials separately in order to compare the results of observational studies and clinical trials using meta-analysis. With the aid of Medline and a manual search in Index Medicus and cross-references of articles published up to July 2003, we identified studies designed to evaluate the effects of heparin on UC. The pooled cure rate in observational studies was calculated. RESULTS: The results of controlled clinical trials evaluated using meta-analysis showed that the pooled cure rate for observational studies was 87.7% (range 80 - 100). The odds ratio for the controlled trial was 0.34 (95% CI 0.08 - 1.49) using a random effects model and 0.21 (95% CI 0.06 - 1.38) using a fixed effects model. The results of meta-analysis demonstrate a non-significant effect of heparin in controlled clinical trials. CONCLUSION: The findings of the clinical trials differ markedly from observational studies and indicate a lack of efficacy of heparin in patients with ulcerative colitis.

Colitis, Ulcerative↗
PubMed2004

Blood pressure in rural and urban adult healthy females of Jat Sikh community in Punjab, North India: an epidemiologic profile.

Blood pressure readings were collected from 1042 adult females of rural and urban Jat Sikh community of Punjab, a north Indian State. Anthropometric measurements like height, weight and skinfold thickness were also collected. The difference between rural and urban females in systolic, diastolic and mean arterial blood pressure was found to be statistically significant. All anthropometric variables and age have a significant positive association with blood pressure. The effects of anthropometric variables on blood pressure were assessed simultaneously through stepwise multiple regression analysis. All 'F' ratios have been found highly significant (p < 0.001) among both rural and urban female population.

Adult↗
PubMed2003

Treatment of infantile hypertrophic pyloric stenosis in a district general hospital: a review of 160 cases.

BACKGROUND: Ramstedt's pyloromyotomy has long been the standard operation for the treatment of infantile hypertrophic pyloric stenosis. Controversy exists over whether this procedure can be performed safely in the district general hospital setting or whether it should be restricted to specialist pediatric units only. METHODS: Retrospective analysis was performed on the medical records of a series of 160 infants treated by Ramstedt's pyloromyotomy by 2 surgeons in a district general hospital over 16 years. RESULTS: There was no perioperative mortality. Oral feeding was achieved by 24 hours in 76% of infants, and there was persistent vomiting in only 3.8%. Wound discharge was encountered in 4.4% and confirmed wound infection in 1.3%. Wound dehiscence occurred in 1.9% of infants. Inadvertent mucosal perforation occurred in 19% of cases, although all cases were recognized and repaired at once with no apparent ill effects. These results are comparable with those reported from specialist pediatric units and from pediatric surgeons working within general surgical units. CONCLUSIONS: Infantile hypertrophic pyloric stenosis can be treated safely in a district general hospital when care is provided by appropriately trained surgical, anesthetic, and pediatric staff.

Digestive System Surgical Procedures↗
PubMed2002

Fatty acid signalling in a mouse enteroendocrine cell line involves fatty acid aggregates rather than free fatty acids.

Fatty acids induce cholecystokinin (CCK) secretion both in humans and from murine enteroendocrine cell lines. In both cases, only fatty acids above a critical acyl chain length (C(10)) are capable of inducing a response. Using the enteroendocrine cell line STC-1, the aim of this study was to determine whether this acyl chain length dependency is related to the fact that longer chain fatty acids are relatively insoluble in aqueous solutions and, if so, whether it is insoluble aggregates of fatty acids rather than free fatty acids which evoke CCK secretion. Solutions of fatty acids (chain length C(8)-C(14)), which were judged by filtration and Zeta sizer measurement to contain no fatty acid aggregates, never evoked CCK secretion from STC-1 cells. Filtering fatty acid solutions (of chain length C(10), C(12) and C(14)) through polytetrafluoroethylene (PTFE) filters (0.45 microm pore size) revealed a narrow concentration range for each acid over which the amount of fatty acid removed from the solution increased sharply due to the formation of fatty acid aggregates. Filtration experiments, in which suspensions of C(10), C(12) and C(14) fatty acids were passed through pore sizes of 0.2, 0.45 or 1.2 microm, suggested that STC-1 cells did not respond to fatty acid aggregates of greater than 1.2 microm, while at least 50 % of the CCK response was mediated by aggregates which were smaller than 0.45 microm. Fatty acids induce CCK secretion from STC-1 cells by elevating intracellular Ca(2+) concentration ([Ca(2+)](i)). We therefore measured the effects on [Ca(2+)](i) of filtered C(10), C(12) and C(14) fatty acids. In all cases, [Ca(2+)](i) responses were closely correlated with CCK secretion. Interestingly, while filtrates of fatty acid solutions evoked CCK secretion and elevated [Ca(2+)](i), freshly prepared solutions of fatty acids at the same concentration as the filtrates did not. This suggested that fatty acid aggregates were not in equilibrium with the solvent after filtration. The observation that the ability of C(10), C(12) and C(14) filtrates to elevate [Ca(2+)](i) decayed with time was consistent with this hypothesis. Furthermore, sonication of the filtrates abolished their ability to elevate [Ca(2+)](i). These data further suggest that it is a physical property of the fatty acid solution (the presence of insoluble fatty aggregates) which is responsible for the observed cellular responses. We conclude that Ca(2+) mobilisation and CCK secretion in STC-1 cells is driven by a signal transduction mechanism that senses insoluble fatty acid aggregates, rather than free fatty acids in solution.

Animals↗
PubMed2001

Mapping protein-protein interactions with combinatorial biology methods.

Extremely diverse, DNA-encoded libraries of peptides and proteins have been constructed that include a linkage between each polypeptide and the encoding DNA. Library members can be selected by virtue of a particular binding specificity, and their protein sequence can be deduced from the sequence of the cognate DNA. Such combinatorial biology methods have proven invaluable in both identifying natural protein-protein interactions and also in mapping the specificities and energetics of these interactions in fine detail.

Amino Acid Sequence↗
PubMed2001

Initial experience of vocal cord evaluation using grey-scale, real-time, B-mode ultrasound.

BACKGROUND: To evaluate whether grey-scale, real-time, B-mode ultrasound (US) is a reliable alternative to nasopharyngoscopy for assessing vocal cord function post-thyroid and post-parathyroid surgery. METHODS: A prospective validation study was undertaken comparing grey-scale, real-time, B-mode vocal cord US with the standard of nasopharyngoscopy in 100 consecutive patients undergoing thyroid and parathyroid surgery between 1 February 1999 and 31 August 1999, with seven patients with known cord palsy. The sensitivity and specificity of grey-scale, real-time vocal cord US for the detection of vocal cord palsy when compared to the standard of nasopharyngoscopy was analysed. RESULTS: In the postsurgical group, there were six nerves (3.2% of the nerves at risk) transient and no permanent vocal cord palsies. US identified four of six transient palsies and reported two false negatives and three false positives. US identified four of seven cord palsies in the non-surgical group with known cord palsy. Analysis of the 107 combined patients showed US had sensitivity of 62% (8/13), specificity of 97% (91/94), a positive predictive value of 73% (8/11) and a negative predictive value of 95% (91/96) for detecting cord paralysis compared to the standard of nasopharyngoscopy. CONCLUSION: Despite the enthusiasm of earlier reports, our initial experience with grey-scale, real-time, B-mode US suggests it is not a reliable alternative to nasopharyngoscopy for assessing vocal cord function post-thyroid and post-parathyroid surgery. Further recruitment of patients with known vocal cord palsy is required to confirm or refute these initial impressions.

Female↗
PubMed2000

Thyroid pathology associated with primary hyperparathyroidism.

BACKGROUND: Thyroid carcinoma and benign thyroid disease associated with primary hyperparathyroidism (PHPT) have been well described. With the developing trend toward minimally invasive parathyroidectomy without intra-operative thyroid gland palpation, thyroid pathology may be missed. The authors consider it timely to revisit the issue of thyroid pathology found at neck exploration for PHPT. METHODS: A retrospective review of all cases of neck exploration for PHPT between 1993 and 1998 at Liverpool Hospital was undertaken. RESULTS: There were 65 patients in the study group (44 women, 21 men; mean age: 59 years). The most common indication for surgery was asymptomatic hypercalcaemia. The mean pre-operative calcium level was 2.9 mmol/L and the mean parathyroid hormone (PTH) level was 17 pmol/L. There were 26 cases (40%) of coexistent thyroid pathology. Ten cases (15%) were of mild multinodular change, seven cases (11%) were of severe multinodular change requiring thyroidectomy, three cases (4%) were nodules secondary to Hashimoto's thyroiditis and six cases (10%) were suspicious nodules that proved to be either adenomas (n = 3) or carcinomas (n = 3) following excision. There were four papillary carcinomas detected in the present series with a mean metastases, age, completeness of excision, invasion size (MACIS) score of 4.92. CONCLUSION: A 25% association of significant thyroid pathology with PHPT is reported. Despite pre-operative tests there were two cases (4%) of thyroid carcinoma where the decision to resect the thyroid gland was made following intra-operative thyroid gland palpation. One of these two papillary carcinoma patients would have fulfilled criteria for minimally invasive parathyroid surgery. When evaluating results of minimally invasive parathyroid surgery one must be aware of the potential for missed thyroid pathology.

Adult↗
PubMed2000

Prospective evaluation of morphology, function, and quality of life after extracorporeal shockwave lithotripsy and endoscopic treatment of chronic calcific pancreatitis.

OBJECTIVE: Therapeutic endoscopy may be effective in selected patients with chronic calcific pancreatitis (CCP). We prospectively evaluated the early outcome of extracorporeal shockwave lithotripsy (ESWL) in combination with interventional endoscopy, using broad inclusion criteria. METHODS: A total of 48 consecutive patients (35 male, 13 female) were recruited for ESWL and endoscopic therapy of symptomatic CCP. Symptoms, quality of life, pancreatic morphology and function were assessed before and after. RESULTS: Multiple stones (n = 43), strictures (n = 34), and pancreas divisum (n = 11) were found. A median of 13 ESWL sessions (range 2-74) with a median of 22,100 shockwaves (1,700-150,900) were required. Endoscopic pancreatic sphincterotomy (n = 48), stricture dilation (n = 12), and/or stenting (n = 27) were performed. After therapy, drainage of the pancreatic duct system was achieved in 36, complete stone clearance in 21 patients. Follow-up (n = 38) at 7 months (range 5-9) showed a significant decrease in pancreatic duct diameter (p < 0.001) and pain score (p < 0.0001) whereas complete pain relief was observed in 45% of cases. Several quality of life scores improved significantly. Weight gain occurred in 68% of patients. Normalization of fasting blood glucose and HbA1c levels were observed in four patients, without modifying their treatment. Improvement in pain score correlated with weight gain and decrease in pancreatic duct diameter. Nonalcoholic etiology was associated with a better chance for improvement in pain score and decrease in pancreatic duct diameter. The presence of strictures did not deteriorate the clinical outcome. CONCLUSIONS: Besides pain relief, ESWL in combination with interventional endoscopy resulted in pancreatic ductal decompression, weight gain, and improvement in quality of life in a considerable number of patients with advanced CCP.

Calculi↗
PubMed1999

Amoxycillin-induced flexural exanthem.

We describe a 37-year-old man who developed an acute, inflammatory flexural eruption shortly after taking amoxycillin, then erythema multiforme-like lesions on the palms and soles. The eruption resolved with systemic corticosteroids, and positive patch tests with amoxycillin supported a drug-induced aetiology. A few similar cases have been described as the 'baboon syndrome' or intertriginous drug eruptions. We draw attention to this rare, distinctive drug eruption.

Adult↗
PubMed1998

Protection of DNA in HL-60 cells from damage generated by hydroxyl radicals produced by reaction of H2O2 with cell iron by zinc-metallothionein.

Scavenging of hydroxyl radicals (.OH) by the zinc form of metallothionein (ZnMT) was studied in HL-60 cells and in nuclei from such cells previously treated with ZnCl2 (ZnMT cells). Cells were grown for 48 h to label DNA for alkaline elusion experiments. During the last 24 h 0.1 mM ZnMT was included to induce ZnMT. Generation of DNA single-strand breaks (SSBs) by H2O2 in cells (5 x 10(5)/ml) treated at 4 degrees was increased by approximately 70% in Zn-treated cells by comparison with control cells. These cells had grown from an initial concentration of 5 x 10(5)/ml to a concentration at harvest of 16 x 10(5)/ml. Cells started at 6 x 10(5)/ml and growing to a final concentration of 20 x 10(5)/ml did not exhibit a similar increase in SSBs. This elevation in SSBs was traced to an increase in cell Fe content which exhibited a sharp dependence upon concentrations of cells and of ZnCl2 at the time of addition. The diffusion distance (d) from Fe to DNA of ZnMT cells treated with H2O2 was found to be 3.4 nm. This compares with a distance of 6.1 nm in control cells. SSB generation by hydroxyl radicals formed by 137Cs-gamma rays in Zn-treated cells decreased by 12%, accompanied by a decrease in d from 4.8 nm to 2.9 nm. Thus, ZnMT preferentially reacts with OH formed at some distance from DNA. In nuclei isolated from ZnMT cells started at 5 x 10(5)/ml, SSB generation by H2O2 increased by 60%. The d in these nuclei was 4.9 nm, similar to the distance in control nuclei reported previously. These data suggest that, in addition to altering the scavenging environment, treatment of cells with Zn leads to an increase in reactive Fe in cells and in isolated nuclei which can generate DNA damage through reaction with H2O2.

Antioxidants↗