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Biomedical subjects

H Patel

Publications and source records attributed to H Patel.

At least 19 recordsLinked to original sources

Role of circulating tumour cells in predicting recurrence after excision of primary colorectal carcinoma.

BACKGROUND: This study assessed the potential for reverse transcriptase-polymerase chain reaction (RT-PCR)-based circulating tumour cell identification to predict colorectal cancer recurrence. METHODS: mRNA for carcinoembryonic antigen and cytokeratin 20 was identified by RT-PCR in blood from patients with colorectal cancer, before and after primary tumour resection. Cancer recurrence was assessed at follow-up, and the accuracy of RT-PCR and primary tumour lymph node positivity in predicting recurrence was estimated. RESULTS: One hundred and ninety-six patients with colorectal cancer were studied over a median follow-up of 1393 days from surgery. Regression analysis selected 24-h post-resection RT-PCR positivity (hazard ratio for a positive test in predicting recurrence 8.66 (95 per cent confidence interval (c.i.) 3.08 to 24.33)) before lymph node involvement (hazard ratio 7.92 (95 per cent c.i. 3.26 to 19.20)). When 24-h post-resection RT-PCR was combined with lymph node positivity, the hazard ratio increased to 18.54 (95 per cent c.i. 4.01 to 85.11), attributing a 3 per cent recurrence risk to 52 per cent, and a 50 per cent recurrence risk to 48 per cent, of patients with colorectal cancer resected with curative intent. CONCLUSION: RT-PCR positivity within 24 h of primary colorectal cancer resection is a strong predictor of colorectal cancer recurrence, and may be useful clinically.

Aged↗

Defining 'full-length' recombinant factor VIII: a comparative structural analysis.

Coagulation factor VIII (FVIII) is an important glycoprotein co-factor involved in haemostasis, functioning to accelerate activation of factor X by activated factor IX. Insertion of expression vectors containing the full-length cDNA sequence of human FVIII into mammalian cell lines results in the production of recombinant factor VIII (rFVIII), typically referred to as 'full-length' rFVIII (FLrFVIII). Both FLrFVIII and plasma-derived FVIII exist primarily as heterodimeric proteins, consisting of a heterogenous light and heavy chain. The objectives of this study were to compare the structural heterogeneity of high-purity FVIII preparations and further define the term 'full length' as it refers to rFVIII protein structure. Five commercially available FVIII concentrates were characterized based on SDS-PAGE, N-terminal sequencing, and peptide and domain mapping coupled to mass spectrometry. The major heavy chain species identified in FLrFVIII included various B-domain-truncated forms of FVIII, with the predominant species terminating at Arg(1313). This study demonstrates that the use of full-sequence FVIII cDNA for the production of rFVIII does not result in a homogeneous FLrFVIII protein product. Rather, commercially available FLrFVIII represents a heterogenous mixture of various B-domain-truncated forms of the molecule, with no evidence of a contiguous, intact B-domain.

Chromatography, High Pressure Liquid↗

Racial or ethnic differences in allele frequencies of single-nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene and their influence on response to methotrexate in rheumatoid arthritis.

BACKGROUND: The anti-folate drug methotrexate (MTX) is commonly used to treat rheumatoid arthritis. OBJECTIVE: To determine the allele frequencies of five common coding single-nucleotide polymorphisms (SNPs) in the methylenetetrahydrofolate reductase (MTHFR) gene in African-Americans and Caucasians with rheumatoid arthritis and controls to assess whether there are differences in allele frequencies among these ethnic or racial groups and whether these SNPs differentially affect the efficacy or toxicity of MTX. METHODS: Allele frequencies in the 677, 1298 and 3 additional SNPs in the MTHFR coding region in 223 (193 Caucasians and 30 African-Americans) patients with rheumatoid arthritis who previously participated in one of two prospective clinical trials were characterised, and genotypes were correlated with the efficacy and toxicity of MTX. Another 308 subjects with rheumatoid arthritis who participated in observational studies, one group predominantly Caucasian and the other African-American, as well as 103 normal controls (53 African-Americans and 50 Caucasians) were used to characterise allele frequencies of these SNPs and their associated haplotypes. RESULTS: Significantly different allele frequencies were seen in three of the five SNPs and haplotype frequencies between Caucasians and African-Americans. Allele frequencies were similar between patients with rheumatoid arthritis and controls of the same racial or ethnic group. Frequencies of the rs4846051C, 677T and 1298C alleles were 0.33, 0.11 and 0.13, respectively, among African-Americans with rheumatoid arthritis. Among Caucasians with rheumatoid arthritis, these allele frequencies were 0.08 (p<0.001 compared with African-Americans with rheumatoid arthritis), 0.30 (p = 0.002) and 0.34 (p<0.001), respectively. There was no association between SNP alleles or haplotypes and response to MTX as measured by the mean change in the 28-joint Disease Activity Score from baseline values. In Caucasians, the 1298 A (major) allele was associated with a significant increase in MTX-related adverse events characteristic of a recessive genetic effect (odds ratio 15.86, 95% confidence interval 1.51 to 167.01; p = 0.021), confirming previous reports. There was an association between scores of MTX toxicity and the rs4846051 C allele, and haplotypes containing this allele, in African-Americans, but not in Caucasians. CONCLUSIONS: : These results, although preliminary, highlight racial or ethnic differences in frequencies of common MTHFR SNPs. The MTHFR 1298 A and the rs4846051 C alleles were associated with MTX-related adverse events in Caucasians and African-Americans, respectively, but these findings should be replicated in larger studies. The rs4846051 SNP, which is far more common in African-Americans than in Caucasians, can also be proved to be a useful ancestry informative marker in future studies on genetic admixture.

Black or African American↗

Delivering results to clients: a question of satisfying needs or desires?

Demand for genitourinary (GU) medicine services is outstripping supply. Improving efficiency can modulate the supply side of the equation, e.g. decreasing the number of clients having to return for their results. This survey explored how clients at two central London GU medicine clinics would like to receive their results and their views were reflected against what was offered by London GU medicine clinics. There was a significant difference between the result delivery services that the clients wanted and what the clinics provided (P <0.0001, chi(2)). Of the clients, 92% wanted to know their results regardless of outcome whereas 22% of London clinics would only inform clients of positive results. This study questions the importance and feasibility of patient choice, an important aspect of the National Strategy for Sexual Health and HIV. Clinics may not individually be able to provide choice but between them, they do provide a wide range of alternatives for the client.

HIV Infections↗

Comprehensive stroke care: an overview.

Stroke is a global epidemic and an important cause of morbidity and mortality. It ranks next to cardiovascular disease and cancer as a cause of death. "India is likely to suffer huge social and economic burden in the rehabilitation of stroke patients owing to increased life expectancy" and urbanization. Though, there are national programs in malaria eradication and tuberculosis control, there is hardly any governmental support in stroke management and rehabilitation. We propose to formulate stroke-prevention strategies specific to our national needs and covering all the age groups. Allocation of resources towards the stroke management and research is needed. Emphasis on stroke awareness in community should be stressed and should be inclusive of means of primordial and primary prevention apart from management of stroke and its recurrence. Recent international experience in stroke management has suggested the need of specialized stroke units (comprehensive stroke care under one roof). We wish to establish the need of creating awareness regarding the urgency of specialized care in acute stroke. We also wish to motivate our national health institutions to offer affordable, evidence based management of stroke and offer opportunities in stroke training and research.

Acute Disease↗

Epinephrine for bronchiolitis.

BACKGROUND: Bronchodilators are commonly used in the management of bronchiolitis. A recent systematic review showed that bronchodilators produce modest short-term benefit among patients with mild or moderate bronchiolitis. OBJECTIVES: To compare epinephrine versus placebo and other bronchodilators in infants less than 2 years of age with bronchiolitis. SEARCH STRATEGY: Electronic searches were conducted on the following bibliographic databases: The Cochrane Central Register of Controlled Trials (CENTRAL) (issue 1, 2003), MEDLINE (January 1966 to May 2003), and EMBASE (January 1988 to May 2003). The reference lists of all selected articles were examined for relevant studies. Primary authors were contacted for information on additional trials. SELECTION CRITERIA: Studies were included if they: 1) were RCTs comparing epinephrine with placebo or other bronchodilator; 2) involved children less than two years with bronchiolitis; 3) presented at least one quantitative outcome. DATA COLLECTION AND ANALYSIS: Searches were screened and inclusion criteria applied independently by two reviewers. Quality was assessed by two reviewers using the Jadad scale and allocation concealment. Data were extracted by one reviewer using a structured form and checked by a second. Separate analyses were conducted for the two types of control groups (placebo, non-epinephrine bronchodilators) and for patient status (inpatient, outpatient). MAIN RESULTS: Fourteen studies were included. Quality ranged from one to five (Jadad scale) with a median of three (inter-quartile range: two to three). Allocation concealment was adequate in six trials and unclear in eight. Among inpatient studies comparing epinephrine and placebo (n = five), there was one significant outcome favouring epinephrine: change in clinical score at 60 minutes post-treatment (SMD -0.52; 95% CI -1.00,-0.03). For outpatient studies (n = three), change in clinical score at 60 minutes (SMD -0.81; -1.56,-0.07), change in oxygen saturation at 30 minutes (WMD 2.79;1.50,4.08), respiratory rate at 30 minutes (WMD -4.54;-8.89-0.19), and "improvement" (OR 25.06; 4.95,126.91) favoured epinephrine. Heart rate at 60 minutes post-treatment favoured placebo (WMD 11.80; 5.20,18.40). Admission rates and change in oxygen saturation at 60 minutes post-treatment were not significantly different. For inpatient studies comparing epinephrine and salbutamol (n = four), only one of the seven outcomes was statistically significant: respiratory rate at 30 minutes favoured epinephrine (WMD -5.12; -6.83;-3.41). Among outpatient studies (n = four), change in oxygen saturation at 60 minutes (WMD 1.91; 0.38,3.44), heart rate at 90 minutes (WMD -14.00; -22.95;-5.05), respiratory rate at 60 minutes (WMD -7.76; -11.35,-4.17) post-treatment and "improvement" (OR 4.51; 1.93,10.53) favoured epinephrine. Admission rates were not significantly different (OR 0.40; 0.12,1.33). Pallor at 30 minutes post-treatment was significantly higher in the epinephrine group (OR 6.00; 1.33,27.00). REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the use of epinephrine for the treatment of bronchiolitis among inpatients. There is some evidence to suggest that epinephrine may be favourable to salbutamol and placebo among outpatients. A number of large, multi-centered trials are required to examine the effectiveness of epinephrine compared to placebo and salbutamol for infants presenting to outpatient settings. There is a need to develop a validated, reliable scoring system that is sensitive to important clinical changes in patients with bronchiolitis.

Albuterol↗

Glucocorticoids for acute viral bronchiolitis in infants and young children.

BACKGROUND: Systemic glucocorticoids have been widely prescribed for use in infants and young children with acute viral bronchiolitis but the actual benefit of this intervention requires clarification. OBJECTIVES: To systematically review the evidence on the effectiveness of systemic glucocorticoids for the treatment of infants and young children with acute viral bronchiolitis. SEARCH STRATEGY: Multiple strategies were incorporated to maximize identification of suitable studies. The following databases were searched: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2003); MEDLINE (January 1966 to September 2003); Current Contents (1998 to 2000); EMBASE (January 1990 to September 2003); and Sci Search. Handsearches through cited references and contacts with experts were also used. SELECTION CRITERIA: Only randomised controlled trials (RCT) were eligible for inclusion. Studies were included if participants were diagnosed with acute viral bronchiolitis and treated with systemic (oral, intramuscular or intravenous) corticosteroids. Three reviewers independently selected potentially relevant articles. Four reviewers evaluated these studies, determined eligibility and assessed the methodological quality of each RCT. DATA COLLECTION AND ANALYSIS: The primary outcome of interest was length of hospital stay (LOS). Secondary outcomes were: respiratory rate, haemoglobin oxygen saturation, and hospital admission and revisit rates. Data were extracted independently by the four reviewers and the results compiled and compared. Two reviewers reassessed studies to clarify points of discrepancy in the data extraction and database entry processes. Missing data were requested from the authors or calculated from other data presented in the study report. MAIN RESULTS: There was complete agreement on the inclusion of 13 trials and the exclusion of five studies. Two main study recruitment groups were identified: a) infants and young children within the first 48 hours of hospitalisation (10 trials), and b) outpatient infants and young children who were randomised from the emergency department and who may nor may not have required hospital admission (three trials).A total of 1,198 children aged 0 to 30 months were treated with the equivalent of 0.5 to 10 mg/kg of systemic prednisone for two to seven days. Outcomes of interest were not measured in each RCT. In the pooled analysis of seven trials, there was a decrease in LOS in treated children of 0.38 days (95% confidence interval (CI) -0.81 to 0.05), indicating no significant difference between treatment groups. In the pooled analysis of eight trials, the day three clinical score measured: a standard mean difference (SMD) of -0.20 (95% CI -0.73 to 0.32), indicating no difference between treatment groups. Subgroup analyses for base LOS and clinical score outcomes were performed on infants who were a) less than 12 months of age, b) all respiratory syncytial virus (RSV) positive, c) treated with less than 6 mg/kg of prednisone equivalent throughout the illness and d) first-time wheezers. These were limited by the small number of studies in each subgroup. Hospital admission rates were examined in three trials and no difference was seen between treatment groups (odds ratio (OR) 1.05 (95% CI 0.23 to 4.87). Readmission rates were reported in six studies; with no significant differences between treatment groups. Hospital revisit rates were reported in three studies, with a significant difference between treatment groups reported in one study only. The respiratory rate and haemoglobin oxygen saturation were reported descriptively in six RCTs; no differences were found between groups. Co-interventions (oxygen, supportive fluids and bronchodilators) were used similarly between treatment groups in all RCTs. REVIEWERS' CONCLUSIONS: No benefits were found in either LOS or clinical score in infants and young children treated with systemic glucocorticoids as compared to placebo. There were no differences in these outcomes between treatment groups; either in the pooled groups; either in the pooled analysis or in any of the sub analyses. Among the three studies evaluating hospital admission rates following the initial hospital visit there was no difference between treatment groups. There were no differences found in respiratory rate, haemoglobin oxygen saturation, hospital revisit or readmission rates. Subgroup analyses were significantly limited by the low number of studies in each comparison. Marked study heterogeneity and occasionally conflicting direction of benefit between trials suggests that these results should be interpreted with caution. Specific data on the harm of corticosteroid therapy in this patient population are lacking. Available evidence suggests that corticosteroid therapy is not of benefit in this patient group.

Acute Disease↗

Preliminary treatment planning and dosimetry for a clinical trial of neutron capture therapy using a fission converter epithermal neutron beam.

A Phase I/II clinical trial of neutron capture therapy (NCT) was conducted at Harvard-MIT using a fission converter epithermal neutron beam. This epithermal neutron beam has nearly ideal performance characteristics (high intensity and purity) and is well-suited for clinical use. Six glioblastoma multiforme (GBM) patients were treated with NCT by infusion of the tumor-selective amino acid boronophenylalanine-fructose (BPA-F) at a dose of 14.0 g/m(2) body surface area over 90 min followed by irradiation with epithermal neutrons. Treatments were planned using NCTPlan and an accelerated version of the Monte Carlo radiation transport code MCNP 4B. Treatments were delivered in two fractions with two or three fields. Field order was reversed between fractions to equalize the average blood boron concentration between fields. The initial dose in the dose escalation study was 7.0 RBEGy, prescribed as the mean dose to the whole brain volume. This prescription dose was increased by 10% to 7.7 RBEGy in the second cohort of patients. A pharmacokinetic model was used to predict the blood boron concentration for determination of the required beam monitor units with good accuracy; differences between prescribed and delivered doses were 1.5% or less. Estimates of average tumor doses ranged from 33.7 to 83.4 RBEGy (median 57.8 RBEGy), a substantial improvement over our previous trial where the median value of the average tumor dose was 25.8 RBEGy.

Aged↗

Effects of boron neutron capture irradiation on the normal lung of rats.

The whole lung of rats was irradiated with X-rays, thermal neutrons, or thermal neutrons in the presence of p-boronophenylalanine (BPA). A >/= 20% increase in breathing rate, in the period 40-80 days after irradiation, was indicative of radiation-induced pneumonitis. The ED(50) (+/-SE) for a >/= 20% increase in breathing rate, relative to age-matched controls, was 11.6 +/- 0.13 Gy for X-rays and 9.6 +/- 0.08 Gy for neutrons only. This indicated a thermal neutron beam RBE of 1.2 and an RBE of 2.2 for the high-LET components of the dose, assuming a dose reduction factor of 1.0 for gamma rays. Preliminary data indicate the compound biological effectiveness factor for BPA in the lung is approximately 1.5.

Animals↗

A penny for your thoughts: small bowel obstruction secondary to coin ingestion.

We report a case of small bowel obstruction secondary to coin ingestion. A 22-year-old woman presented to the Emergency Department (ED) with a 3-week history of abdominal pain. Upon initial history the patient denied any foreign body ingestion. Only after computed tomography (CT) scanning of the abdomen and pelvis did the patient admit to deliberate ingestion of a single United States penny coin. During surgical evaluation it was found that the coin had lodged near the ileocecal valve and an inflammatory mass had formed around the intraluminal coin, causing a 10 x 7 cm fibrous tumor to completely obstruct the small bowel. It is thought that oxidation of the coin, with subsequent exposure of its high zinc content, instigated the inflammatory cascade.

Abdomen, Acute↗

Contrast-enhanced cardiac magnetic resonance in a patient with familial isolated ventricular non-compaction.

Isolated ventricular non-compaction (IVNC) is an idiopathic form of cardiomyopathy. Recent clinical reports have suggested that this form of cardiomyopathy is more frequently associated with complications of congestive heart failure, thromboembolism and malignant ventricular arrhythmias. Contrast enhanced cardiac magnetic resonance imaging with its excellent spatial resolution, its large field of view and its ability to demonstrate thrombus and myocardial scar is an excellent modality to non-invasively assess patients with this form of cardiomyopathy. This paper presents a case of familial isolated ventricular non-compaction. We describe the echocardiographic, X-ray angiographic and cardiac MRI findings. Cine imaging using a steady-state free precession sequence (BFFE) was performed in axial and short axis planes. Left ventricular (LV) mass was estimated both with and without the incorporation of trabeculations from a contiguous stack of short axis images. Trabecular mass was expressed as a percentage of total left ventricular mass. We compared trabecular mass: total LV mass in 10 patients with dilated cardiomyopathy. The mean percentage trabecular mass: LV mass in dilated cardiomyopathy was 11.3% (range 1.5%-19%), and this differed significantly from the trabecular mass of the noncompaction patient (two-tailed Mann-Whitney test, p = 0.028). Trabecular mass of greater than 20% of total myocardial mass may be a useful index to suggest the diagnosis of IVNC. Gadolinium was administered (0.1 mmol/kg). Qualitative analysis of first pass perfusion suggested reduced trabecular perfusion. Early imaging with an inversion recovery sequence and a fixed long inversion time did not demonstrate LV thrombus. Late imaging with the same sequence (TI = 280-300 msec) did not demonstrate myocardial fibrosis.

Adult↗

Attitudes towards the use of hand over mouth (HOM) and physical restraint amongst paediatric specialist practitioners in the UK.

PURPOSE: To assess the views of paediatric specialist dental practitioners in the United Kingdom of the use of the hand over mouth technique and physical restraint. METHODS: Questionnaire survey of all specialist dental practitioners in paediatric dentistry in the United Kingdom (n = 216). Replies were received from 179 individuals (82.8%). RESULTS: The majority of the sample (over 80%) described HOM as having three components, broadly mirroring the description of the technique in clinical textbooks. Approximately 60% of the respondents reported that HOM should never be used (106 individuals, 59.2%). Those who endorsed the use of HOM suggested it should be used with cases of hysterical, tantrum behaviour (57 respondents, 32%). The use of physical restraint was endorsed for certain disabled patients by 110 individuals (62%); for very young patients by 69 respondents (39%); premedicated patients by 35 respondents (20%); physically resistive patients by 25 respondents (14%). Forty-three respondents (24%) felt there were no psychological consequences of the use of HOM or physical restraint; 91 (51%) felt that HOM would result in the child fearing dental treatment. CONCLUSIONS: Specialist paediatric dental practitioners in the UK are familiar with the technique of HOM although they also feel that this technique should never be used. A large proportion of practitioners felt that the use of physical restraint was appropriate with certain disabled patients. The most commonly anticipated psychological sequeala which may accompany the use of these techniques was subsequent fear of dental treatment.

Attitude of Health Personnel↗