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Biomedical subjects

M K Sidhu

Publications and source records attributed to M K Sidhu.

At least 19 recordsLinked to original sources

Surgery for morbid obesity.

BACKGROUND: Obesity is associated with increased morbidity and mortality. Surgery for morbid obesity is considered when other treatments have failed. A number of procedures are available, but the effects of these surgical procedures compared with medical management and with each other are uncertain. OBJECTIVES: To assess the effects of surgery for morbid obesity. SEARCH STRATEGY: Studies were obtained from computerized searches of multiple electronic bibliographic databases, supplemented with hand searches of selected journals and consultation with experts in obesity research. Date of the most recent searches: December 2004. SELECTION CRITERIA: Randomised controlled trials comparing different surgical procedures, and randomised controlled trials and prospective cohort studies comparing surgery with non-surgical management for morbid obesity. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and checked independently by two reviewers. Two reviewers independently assessed trial quality. MAIN RESULTS: Twenty-six trials were included. Two randomised controlled trials and three prospective cohort studies compared surgery with non-surgical management, and 21 randomised controlled trials compared different surgical procedures. The quality of most of the trials was poor; just three trials had adequate allocation concealment. A meta-analysis was not possible due to differences in the surgical procedures performed, measures of weight change and length of follow-up. Compared with conventional management, surgery resulted in greater weight loss (21 kg weight loss at eight years versus weight gain), with improvements in quality of life and comorbidities. Some complications of surgery occurred, such as wound infection. Gastric bypass was associated with greater weight loss, better quality of life and fewer revisions, reoperations and/or conversions than gastroplasty, but had more side-effects. Greater weight loss and fewer side-effects and reoperations occurred with adjustable gastric banding than vertical banded gastroplasty, but laparoscopic vertical banded gastroplasty produced more patients with an excellent or good result and fewer late complications than laparoscopic adjustable silicone gastric banding. Vertical banded gastroplasty was associated with greater weight loss but more vomiting than horizontal gastroplasty. Some postoperative deaths occurred in the studies. Weight loss was similar between open and laparoscopic procedures. Fewer serious complications occurred with laparoscopic surgery, although conversion to open surgery was sometimes required. Most studies found that laparoscopic surgery had a longer operative time. But, it resulted in reduced blood loss and quicker recovery. AUTHORS' CONCLUSIONS: The limited evidence suggests that surgery is more effective than conventional management for weight loss in morbid obesity. The comparative safety and effectiveness of different surgical procedures is unclear.

Gastric Bypass↗

Systematic review of the Sugarbaker procedure for pseudomyxoma peritonei.

BACKGROUND: Pseudomyxoma peritonei, a rare progressive disease process within the peritoneum, is characterized by an abundance of mucinous fluid; if left untreated, the condition is fatal. The aim of this article is to assess the clinical effectiveness and costs of the Sugarbaker procedure for pseudomyxoma peritonei. METHODS: A systematic review of the literature up to April 2004 was undertaken, with modelling of costs. RESULTS: Five retrospective case-series reports met the inclusion criteria. Survival after operation was approximately 95 per cent at 2 years and 60-68 per cent at 10 years, with 41-52 per cent of patients having no evidence of disease at the end of follow-up. A Monte Carlo simulation model estimated the marginal cost for one patient over a maximum of 5 years to be about pound 9700 (standard deviation pound 1300). CONCLUSION: Evidence of the effectiveness of the Sugarbaker procedure for pseudomyxoma peritonei is limited in quantity and quality, but suggests there may be some benefit for patients. The marginal cost of the operation is about pound 9700, provided that trained and experienced staff are available to perform the procedure.

Costs and Cost Analysis↗

Clinical effectiveness and costs of the Sugarbaker procedure for the treatment of pseudomyxoma peritonei.

OBJECTIVES: This systematic review examines the clinical and cost-effectiveness of the Sugarbaker procedure for treating pseudomyxoma peritonei (PMP) and the costs of the procedure in the UK. DATA SOURCES: Electronic databases, bibliographies of related papers and experts in the field were used as sources for English language studies available up to September 2002. REVIEW METHODS: Evidence of the clinical effectiveness of the Sugarbaker procedure for PMP was synthesised through a narrative review with full tabulation of results of all included studies. The economic modelling used a Monte-Carlo simulation model populated with UK price data to estimate likely UK costs. RESULTS: Five retrospective case-series reports assessing the Sugarbaker procedure met the inclusion criteria for the review, although they were found to be of poor quality when judged against standard criteria for assessing methodological standard. There appears to be some benefit for people with PMP who undergo treatment with the Sugarbaker procedure. Commonly reported complications of the Sugarbaker procedure were anastomotic leaks, fistula formation, wound infection, small bowel perforations/obstructions and pancreatitis. One costing study of poor methodological quality and set in the USA was found. This study, together with UK unit price data and expert advice, was used to populate a Monte-Carlo simulation model to estimate the marginal cost of operating a service to provide treatment for PMP using the Sugarbaker technique rather than standard treatment. The results of the Monte-Carlo simulation model showed that the cost for one patient over a maximum of 5 years would be about 9700 British pounds, with a standard deviation of about 1300 British pounds (although costs incurred in setting up the specific service or training the staff were not included). The US study showed a ten-fold higher cost. The Monte-Carlo analysis showed that the variation around the mean was not very high. The most likely factor influencing the variation of the costs was the length of procedure. No sensitivity analysis could be done of the alternative treatment. CONCLUSIONS: The economic results should be seen as merely an example of the likely marginal costs of the Sugarbaker procedure, as more information about the current alternative is required. Trained and experienced staff are required to implement the procedure and inevitably time and cost will be involved in developing the appropriate teams. Although the procedure requires some specialist equipment and maintenance, such as smoke evacuators, these should have limited effect on setting up the service. PMP is a relatively rare condition with approximately 50 new cases per year in the UK and the impact of an increase in the demand for services should be limited. Evidence is needed for the effectiveness of maximal cytoreductive surgery compared with surgical debulking, using different intraoperative intraperitoneal chemotherapy strategies, and for the effectiveness of treatments in patients who have residual disease following maximal efforts at cytoreduction. Further research involving high-quality prospective cohort studies with economic evaluations would be valuable.

Adult↗

Clinical and cost-effectiveness of continuous subcutaneous insulin infusion for diabetes.

OBJECTIVES: To assess the clinical and cost-effectiveness of continuous subcutaneous insulin infusion (CSII) compared with multiple daily injections (MDI) in the delivery of intensive insulin therapy for the treatment of diabetes mellitus. DATA SOURCES: Electronic databases, references of retrieved articles and manufacturer submissions. Experts in the field were consulted. REVIEW METHODS: For the systematic review of clinical and cost-effectiveness, studies were assessed for inclusion according to predefined criteria by two reviewers. Data extraction and quality assessment were undertaken by one reviewer and checked by a second reviewer. Data on clinical effectiveness were synthesised through a narrative review with full tabulation of all eligible studies, with meta-analysis performed where appropriate. RESULTS: Twenty studies comparing CSII with MDI were identified. Quality was generally poor. In adults with Type 1 diabetes, glycated haemoglobin improved by 0.61% (95% CI -1.29 to 0.07) in longer term studies, although this improvement was smaller when a study using bovine ultralente was excluded. A reduction in insulin dose with CSII of about 12 units per day (-11.90, 95% CI -18.16 to 5.63) was found in short-term studies, with smaller differences in longer term studies. Body weight and cholesterol levels were similar between treatments. Hypoglycaemic events did not differ significantly between CSII and MDI in most trials, but some found fewer events with CSII and one found more hypoglycaemia and hypoglycaemic coma with CSII. There was no consistency between the studies in patient preference, but progress has been made both with insulin pumps and injector pens since the publication of many of the older studies. No difference in glycated haemoglobin between CSII and MDI was found in pregnancy; one study found less insulin was required by patients with CSII, but two other studies found no significant difference. One study of adolescents found lower glycated haemoglobin and insulin dose with CSII whereas a second study found no significant difference. In CSII analogue insulin was associated with lower glycated haemoglobin levels than soluble insulin. No economic evaluations comparing CSII with MDI were identified. The estimated additional cost of CSII compared to MDI varies from GBP1091 per annum to GBP1680 per annum, according to the make of the insulin pump and the estimated life of the device. These estimates include the costs for the insulin pump, the consumables associated with delivery of CSII, and an allowance for the initial education required when patients switch from MDI to CSII. The largest component of the annual cost for CSII is the cost of consumable items (e.g. infusion sets). CONCLUSIONS: When compared with optimised MDI, CSII results in a modest but worthwhile improvement in glycated haemoglobin in adults with Type 1 diabetes. It has not been possible to establish the longer term benefits of such a difference in glycated haemoglobin, although there is an expectation that it would be reflected in a reduction in long-term complications. More immediate primary benefits from CSII may be associated with an impact on the incidence of hypoglycaemic events and the dawn phenomenon, and greater flexibility of lifestyle. However, there is limited evidence on this, and information presented to offer context on quality-of-life is based on testimonies from those patients who have had a positive experience of CSII. The estimated cost to the NHS per year for CSII would be around GBP3.5 million in England and Wales if 1% of people with Type 1 diabetes used CSII, GBP10.5 million for 3%, and GBP17.5 million for 5%. Further research should focus on wider benefits of CSII, such as flexibility of lifestyle and quality of life, and on the psychological impact of wearing a device for 24 hours every day. Research into the use of CSII in children of different ages is also needed.

Cost-Benefit Analysis↗

Power Doppler imaging of acute renal transplant rejection.

PURPOSE: We evaluated the usefulness of power Doppler imaging (PDI) in diagnosing acute renal-transplant rejection. METHODS: Twenty-eight patients underwent 33 renal-transplant biopsies for suspected acute rejection. Patterns of renal parenchymal vascularity revealed by PDI in patients with abnormal biopsy results were compared with patterns in a group who had normal biopsy results. PDI examinations were reviewed retrospectively by 2 independent radiologists who had no knowledge of the biopsy results. A PDI diagnosis of acute rejection required marked vascular pruning in both the cortex and medulla. PDI results then were compared with transplant-biopsy results. RESULTS: The sensitivity and specificity of PDI for diagnosing acute renal-transplant rejection were 40% and 100%, respectively. None of the patients with negative biopsy results had PDI abnormalities. The negative predictive value of PDI was 33%, and the positive predictive value was 100%. CONCLUSIONS: In our study, an abnormal sonogram was highly predictive of acute transplant rejection. However, a normal sonogram did not exclude the possibility of rejection.

Acute Disease↗

Post-traumatic hepatic pseudoaneurysms in children.

BACKGROUND: Post-traumatic hepatic artery pseudoaneurysms are rarely seen in children. MATERIALS AND METHODS: We retrospectively reviewed the radiologic studies and medical records of three patients treated at our institution and reviewed the literature. The patients (ages 5-13 years) presented immediately to 2 months after blunt (two patients) and penetrating (one patient) trauma. The hepatic pseudoaneurysms were discovered during work-up for fever (one patient), gastrointestinal bleeding and hyperbilirubinemia (one patient), or widened mediastinum (one patient) on chest radiograph. In two patients, the diagnosis was initially suspected by computed tomography (CT) examination and confirmed by angiography. In the third patient, the diagnosis was made initially by angiography. All three pseudoaneurysms were treated with transcatheter embolization. RESULTS: All three embolizations were initially technically successful. However, there was recurrence in one case, in which embolization distal to the neck of the pseudoaneurysms was not technically possible. With conservative management, however, the residual lesion demonstrated spontaneous occlusion by ultrasound (US) at 6 months. CONCLUSION: This uncommon complication of liver trauma in children can have a delayed presentation, can be clinically unsuspected, and can follow blunt or penetrating trauma. Endovascular embolotherapy is the treatment of choice.

Abdominal Injuries↗

A new contained human immunodeficiency virus type 1 host cell system for evaluation of antiviral activities of interferons and other agents in vitro.

HIV-host infection systems in vitro are important in the pre-clinical assessment of anti-retroviral drug activity. The present report describes the development of a new HIV-host model comprised of an epithelial cell line of HeLa lineage (HeLa-1), transfected with expression vectors bearing tat and rev (TART) genes of HIV-1 as well as the CD4 receptor gene, and HIV-1(delta Tat/Rev), a biologically contained strain of HIV-1 deleted in tat and rev. Measurement of infectivity, by syncytium formation and reverse transcriptase assay, revealed that HeLa-1 is infected with HIV-1(deltaTat/Rev). This virus failed to productively infect the TART-deficient CD4-positive HeLa cells, confirming its contained, non-infectious nature. The HeLa-1/HIV-1deltaTat/Rev system was used to measure the anti-retroviral activity of a human leukocyte-derived interferon (IFN-alphan3) preparation, several nucleoside analogs, and protease inhibitors. The HeLa-1/ HIV-1(deltaTat/Rev model provides a biologically contained system for the study of the HIV pathogenesis and the relative and combined therapeutic effects of anti-retroviral agents in vitro.

Anti-HIV Agents↗

Identification of copper-zinc superoxide dismutase gene from enteroaggregative Escherichia coli.

We describe here the identification of sodC gene from enteroaggregative Escherichia coli (EAggEC). A 294 bp gene-specific fragment was amplified from the organism by DNA as well as RT-PCR using primers from bacterial sodC sequences. The metal co-factor present in the protein was confirmed by running samples in native gels and inhibiting with 2 mM potassium cyanide. However, the nonpathogenic E. coli possesses the gene but does not express it. Thus, the presence of copper-zinc superoxide dismutase encoded by sodC was demonstrated for the first time in EAggEC, which means it could be a novel candidate for a virulence marker.

Copper↗

Effects of components of meals (carbohydrate, fat, protein) in causing postprandial exertional angina pectoris.

We have shown that unlike fat, protein, xylose, or water, the carbohydrate component of the meal accelerates myocardial ischemia, reduces exercise capacity, and is associated with a more rapid increase in the determinants of myocardial oxygen consumption than exercise in the fasting state. Our results suggest a role for a larger increase in sympathetic nervous activity and/or release of vasoactive gastrointestinal peptides after carbohydrate, but not fat or protein, meals in postprandial angina.

Angina Pectoris↗

Competitor internal standards for quantitative detection of mycoplasma DNA.

Homologous internal controls were used as competitor DNA in the polymerase chain reaction for the quantitative detection of mycoplasma DNA. PCR primer sets were designed on the basis of the most conserved nucleotide sequences of the 16S rRNA gene of mycoplasma species. Amplification of this gene was examined in five different mycoplasma species: Mycoplasma orale, M. hyorhinus, M. synoviae, M. gallisepticum and M. pneumoniae. To evaluate the primers, a number of different cell lines were assayed for the detection of mycoplasma infections. All positive cell lines showed a distinct product on agarose gels while uninfected cells showed no DNA amplification. Neither bacterial nor eukaryotic DNA produced any cross-reaction with the primers used, thus confirming their specificity. Internal control DNA to be used for quantitation was constructed by modifying the sizes of the wild-type amplified products and cloning them in plasmid vectors. These controls used the same primer binding sites as the wild-type and the amplified products were differentiated by a size difference. The detection limits for all the mycoplasma species by competitive quantitative PCR were estimated to range from 4 to 60 genome copies per assay as determined by ethidium bromide-stained agarose gels. These internal standards also serve as positive controls in PCR-based detection of mycoplasma DNA, and therefore accidental contamination of test samples with wild-type positive controls can be eliminated. The quantitative PCR method developed will be useful in monitoring the progression and significance of mycoplasma in the disease process.

Base Sequence↗

Preclinical evaluation of gadolinium (III) texaphyrin complex. A new paramagnetic contrast agent for magnetic resonance imaging.

RATIONALE AND OBJECTIVES: Gadolinium III texaphyrin (Gd[III] texaphyrin) complex, a new magnetic resonance imaging contrast (MRI) agent, was evaluated. METHODS: In vitro relaxivity (1.5 T) and stability studies (5% dextrose) were conducted. Subchronic toxicity (8 males, 8 females; 2-20 mumol Gd(III) texaphyrin complex/kg body weight; 3 times per week for 3 weeks). Biodistribution and excretion studies were conducted in Sprague-Dawley rats; MRI studies were conducted in normal and tumor-bearing rats and rabbits. RESULTS: Relaxivity values were as follows: r1 = 19 (mumol/L.sec)-1 and r2 = 22 (mumol/L.sec)-1. The 21-day subchronic toxicity study revealed no abnormalities. The compound is stable. Biodistribution demonstrated liver uptake. Magnetic resonance imaging in normal (n = 34) and tumor-bearing (n = 4) rats and normal (n = 8) and tumor-bearing (n = 19) rabbits revealed: significant (P < .05) contrast enhancement of liver and kidney after 1-17 mumol/kg of Gd(III) texaphyrin complex. Gadolinium (III) texaphyrin complex (2.5 mumol/kg) produced significant contrast enhancement of liver carcinomas in rabbits (n = 8). Thigh V2 carcinomas (n = 22) had selective (P < .05) enhancement, 5 mumol/kg. In rat fibrosarcomas (n = 4), 17 mumol Gd(III) texaphyrin complex produced significant enhancement up to 24 hours. CONCLUSIONS: Gadolinium (III) texaphyrin complex appears to be an effective and safe MRI contrast agent.

Animals↗

Transformation of immortal, non-tumorigenic osteoblast-like human osteosarcoma cells to the tumorigenic phenotype by nickel sulfate.

Epidemiological studies have indirectly linked compounds of chromium, nickel and arsenic to human carcinogenesis. However, there is no evidence that metal compounds can transform human cells to the tumorigenic phenotype in culture. We show here that exposure to 36 microM NiSO4 for 48-96 h results in transformation of an immortal, nontumorigenic, osteoblast-like cell line, HOS TE85, to the tumorigenic phenotype. Continuous passaging following treatment leads to the formation of a few dense foci. The cells isolated and expanded from the foci are morphologically transformed, and form anchorage-independent colonies of the size and abundance comparable to that formed by Kirsten murine sarcoma virus transformed HOS TE85 cells. The transformed cells from tumors in nude mice, have enhanced levels of plasminogen activators and have lost the ability to form model bone matrix on extended culture in the presence of ascorbic acid and beta-glycerophosphate. A number of cell lines have been established from nude mouse tumors. Cytogenetic analysis reveals 16 marker chromosomes and an aberrant chromosome 16. This is the first report of the transformation of a human cell line to tumorigenic phenotype by a metal carcinogen.

Animals↗

Manganese dipyridoxal diphosphate-enhanced magnetic resonance imaging in the evaluation of hepatocyte function.

RATIONALE AND OBJECTIVES: To determine whether contrast-enhanced magnetic resonance imaging can detect ethanol hepatotoxicity in rats. METHODS: Rats were treated with a single high dose of ethanol (acute) intraperitoneally or with a 36% ethanol diet (chronic) for up to 5.5 months. Magnetic resonance imaging was performed before and after intravenous administration of manganese dipyridoxal diphosphate (Mn-DPDP). RESULTS: Enhancement (acute group) was significantly lower in ethanol treated animals on T1-weighted scans (P < .02). Precontrast, a significant difference in intensity was seen on T2-weighted scans (P < .01). Electron microscopy revealed severe hepatocyte damage. In the chronic groups, there was no significant difference in intensity precontrast. Postcontrast, enhancement (ethanol group) was significantly lower on T1-weighted scans only at 2 weeks (P < .05). Electron microscopy demonstrated progressive ethanol hepatotoxicity. CONCLUSIONS: Magnetic resonance imaging can distinguish between normal and certain types of ethanol damaged livers on T1-weighted scans. Enhancement, however, does not correlate with progressive microscopic liver damage.

Animals↗