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Biomedical subjects

A Patel

Publications and source records attributed to A Patel.

At least 37 records · Page 2Linked to original sources
PubMed2005

Congenital diaphragmatic hernia in WAGR syndrome.

Wilms tumor, aniridia, genitourinary anomalies, and mental retardation (WAGR) syndrome is a contiguous gene deletion syndrome involving the Wilms tumor 1 gene (WT1), the paired box gene 6 (PAX6), and possibly other genes on chromosome 11p13. WT1 is required for normal formation of the genitourinary system and the high incidence of Wilms tumor and genitourinary anomalies found in patients with WAGR are attributed to haploinsufficiency of this gene. It has been hypothesized that WT1 also plays an important role in the development of the diaphragm. During mammalian embryonic development, WT1 is expressed in the pleural and abdominal mesothelium that forms part of the diaphragm. Furthermore, mice that are homozygous for a deletion in the mouse homolog of WT1 have diaphragmatic hernias. Case reports describing congenital diaphragmatic hernias in infants with Denys-Drash and Frasier syndromes, both of which can be caused by mutations in WT1, provide additional support for this hypothesis. We report an infant with aniridia, bilateral cryptorchidism, vesicoureteral reflux, and a right-sided Morgagni-type diaphragmatic hernia. G-banded chromosome analysis revealed a deletion of 11p12-p15.1. Breakpoint regions were refined by fluorescence in situ hybridization (FISH) and deletion of the WAGR critical region, including WT1, was confirmed. A review of the medical literature identified a second patient with a deletion of 11p13, a left-sided Bochdalek-type diaphragmatic hernia, and anomalies that suggest a diagnosis of WAGR including bilateral microphthalmia, a small penis, bilateral cryptorchidism, and a hypoplastic scrotum. These cases demonstrate that congenital diaphragmatic hernia can be associated with WAGR syndrome and suggest that deletions of WT1 may predispose individuals to develop congenital diaphragmatic hernia.

Abnormalities, Multiple↗
PubMed2005

Low factor XII level in an individual with Sotos syndrome.

Sotos syndrome is an overgrowth disorder that manifests characteristic dysmorphic features, neurological problems, and an increased risk for cancers and heart defects. Alterations of NSD1 are responsible for this disease. A subset of cases arise from deletions, which is of interest as the factor XII locus lies in close proximity to NSD1. This case report describes an individual with Sotos syndrome and factor XII deficiency, providing a potential link between these two genes and, consequently, expanding the clinical phenotype of Sotos syndrome.

Abnormalities, Multiple↗
PubMed2005

A comparison of lipid variables as predictors of cardiovascular disease in the Asia Pacific region.

PURPOSE: Many guidelines advocate measurement of total or low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), and triglycerides (TG) to determine treatment recommendations for preventing coronary heart disease (CHD) and cardiovascular disease (CVD). This analysis is a comparison of lipid variables as predictors of cardiovascular disease. METHODS: Hazard ratios for coronary and cardiovascular deaths by fourths of total cholesterol (TC), LDL, HDL, TG, non-HDL, TC/HDL, and TG/HDL values, and for a one standard deviation change in these variables, were derived in an individual participant data meta-analysis of 32 cohort studies conducted in the Asia-Pacific region. The predictive value of each lipid variable was assessed using the likelihood ratio statistic. RESULTS: Adjusting for confounders and regression dilution, each lipid variable had a positive (negative for HDL) log-linear association with fatal CHD and CVD. Individuals in the highest fourth of each lipid variable had approximately twice the risk of CHD compared with those with lowest levels. TG and HDL were each better predictors of CHD and CVD risk compared with TC alone, with test statistics similar to TC/HDL and TG/HDL ratios. Calculated LDL was a relatively poor predictor. CONCLUSIONS: While LDL reduction remains the main target of intervention for lipid-lowering, these data support the potential use of TG or lipid ratios for CHD risk prediction.

Adult↗
PubMed2005

A comparison of lidocaine 2% with levobupivacaine 0.75% for sub-Tenon's block.

BACKGROUND AND OBJECTIVE: To compare the onset of action, and quality of block, of lidocaine 2% with levobupivacaine 0.75% for sub-Tenon's block in patients undergoing cataract surgery. METHODS: We performed a two-centre trial in 91 patients who were randomized to receive 4 mL of lidocaine 2% (n = 44) or levobupivacaine 0.75% (n = 47) for sub-Tenon's block, both with hyaluronidase 15 IUmL(-1). Onset of akinesia was assessed every 2 min for 10 min. Numbers of patients requiring supplementary injections to achieve clinically satisfactory akinesia or rescue analgesia were recorded. Data were analyzed with Fisher's exact test, U-test and t-test where appropriate. Results were considered significant when P < 0.05. RESULTS: The speed of onset was statistically significantly faster for lidocaine compared to levobupivacaine (3.02 vs. 5.06 min, P < 0.001). There was no statistical difference in number of patients requiring a supplementary injection of local anaesthetic (levobupivacaine 3 vs. lidocaine 0, P = 0.24), rescue analgesia with topical tetracaine (levobupivacaine 0 vs. lidocaine 2, P = 0.5), or ocular akinesia scores at the completion of surgery (lidocaine 1.4 vs. levobupivacaine 1.6, P = 0.12). Pain scores measured by a verbal analogue scale were not significantly different for injection, perioperatively or postoperatively. CONCLUSIONS: Both agents produce a rapid onset of anaesthesia when used for sub-Tenon's block. The difference between the two agents, although statistically significant, is not clinically important.

Aged↗
PubMed2005

ADVANCE: action in diabetes and vascular disease.

The burden of Type II diabetes is growing rapidly worldwide, across high-, middle- and low-income countries. This burden is associated primarily with increased risks of macrovascular and microvascular diseases, and it is agreed that multifactorial treatment regimens are required to reduce it. ADVANCE (Action in Diabetes and Vascular disease: Preterax and Diamicron-MR Controlled Evaluation) is a large-scale, 2 x 2 factorial, randomised clinical trial. It will investigate the potential benefits of blood pressure lowering, using a fixed low-dose combination of perindopril and indapamide vs placebo, and of tighter glucose control, using an intensive gliclazide-MR-based glucose control regimen vs a standard guidelines-based regimen, separately and together. The two primary outcomes are a composite macrovascular end point of nonfatal stroke, nonfatal myocardial infarction and cardiovascular death; and a composite microvascular end point of new or worsening nephropathy or microvascular eye disease. Following successful recruitment and randomisation of 11,140 participants by March 2003, the study is currently half way through its planned follow-up of 4.5 years. Adherence to randomised study treatment is good; and loss to follow-up is minimal. It is hoped that the study will answer a number of unresolved issues. The blood pressure lowering arm will investigate the possible reduction in major vascular disease in patients with Type II diabetes whether or not they have hypertension, and the possible benefits of blood pressure lowering in such patients already receiving background therapy with the ACE inhibitor perindopril. The glucose control arm will investigate the possible reduction in both macrovascular and microvascular disease achieved with tighter glucose control, targeting an HbA1c of 6.5% and a fasting blood glucose of 6.0 mmol/l. Finally, the factorial design will enable investigation of the combined effects of more intensive glucose control and tighter control of blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

A potential novel marker for human prostate cancer: voltage-gated sodium channel expression in vivo.

Functional expression of voltage-gated sodium channel alpha-subunits (VGSCalphas), specifically Nav1.7, is associated with strong metastatic potential in prostate cancer (CaP) in vitro. Furthermore, VGSC activity in vitro directly potentiates processes integral to metastasis. To investigate VGSCalpha expression in CaP in vivo, immunohistochemistry and real-time PCR were performed on human prostate biopsies (n>20). VGSCalpha immunostaining was evident in prostatic tissues and markedly stronger in CaP vs non-CaP patients. Importantly, RT-PCRs identified Nav1.7 as the VGSCalpha most strikingly upregulated (approximately 20-fold) in CaP, and the resultant receiver-operating characteristics curve demonstrated high diagnostic efficacy for the disease. It is concluded that VGSCalpha expression increases significantly in CaP in vivo and that Nav1.7 is a potential functional diagnostic marker.

Biomarkers, Tumor↗
PubMed2005

Computer analysis of upper gastrointestinal endoscope images.

Gastro-oesophageal reflux disease (GORD) occurs in up to 40% of adults in the West. Oesophagitis is a major determinant in the treatment of GORD but its current classification systems are subjective. In order to help to provide objective interpretation of upper gastro-intestinal (GI) endoscope examination and reduce inter-observer variability, we developed a computer image analysis system. Digital video recordings were made on patients with clinical evidence of reflux oesophagitis. Cross-sectional profiles of hue and saturation data were analysed on images from seven patients with grade B or C oesophagitis (LA grading). This analysis showed clear changes in hue (p = 0.01) and saturation (p = 0.001). These results suggest that quantification of upper GI endoscopic images is feasible and may help in objective assessment.

Journal Article↗
PubMed2005

Health-related quality of life after retroperitoneoscopic and hand-assisted laparoscopic nephrectomy.

BACKGROUND AND PURPOSE: The assessment of postoperative recovery typically involves the use of measures that are open to bias. Whilst there has been some work done on the short-term postoperative recovery comparison for hand-assisted laparoscopic nephrectomy (HALN) and retroperitoneoscopic nephrectomy (RPN), to our knowledge, this is the first study to look at long-term health outcomes for these two procedures. This study sought objectively to compare long-term postoperative health-related quality of life (HRQoL) after retroperitoneoscopic and hand-assisted transperitoneal laparoscopic nephrectomy undertaken for renal pathology. This was achieved by both reviewing perioperative data from medical records and by using the SF-36 questionnaire postoperatively. PATIENTS AND METHODS: Patients who had undergone elective retroperitoneoscopic (N = 19) or transperitoneal HALN (N = 32) between 2001 and 2004 at our institution underwent objective HRQoL assessment via a validated telephone questionnaire (SF-36) and by review of postoperative data from the medical records. This survey was administered between 3 and 6 months after surgery. The data then underwent statistical analysis using the paired Student's t-test. RESULTS: Perioperative data showed no significant difference in the postoperative complication rate in the two groups. The HRQoL scores gathered from the SF-36 questionnaire gave mean scores of 67.4 and 68.5 for the HALN and RPN groups, respectively (100 represents maximum quality of life). This difference was not statistically significant. CONCLUSIONS: This is the first study to look at long-term (mean follow-up 6 months) health outcomes for patients undergoing RPN and HALN. The results show no greater long-term health benefit for one procedure over the other. This finding supports the data in the literature on the benefits of HALN over RPN in terms of a less protracted learning curve, greater technical ease, fewer intraoperative complications, and consequently reduced operating times with no loss of the long-term health benefit that is traditionally associated with the standard laparoscopic technique.

Female↗
PubMed2005

A prospective, randomized, placebo controlled, double-blind study of pelvic electromagnetic therapy for the treatment of chronic pelvic pain syndrome with 1 year of followup.

PURPOSE: Male chronic pelvic pain syndrome is a condition of uncertain etiology and treatment is often unsatisfactory. There is evidence that the symptom complex may result from pelvic floor muscular dysfunction and/or neural hypersensitivity/inflammation. We hypothesized that the application of electromagnetic therapy may have a neuromodulating effect on pelvic floor spasm and neural hypersensitivity. MATERIALS AND METHODS: Following full Stamey localization men with National Institute of Diabetes and Digestive and Kidney Diseases category III prostatitis were prospectively randomized to receive active electromagnetic or placebo therapy. Active therapy consisted of 15 minutes of pelvic floor stimulation at a frequency of 10 Hz, followed by a further 15 minutes at 50 Hz, twice weekly for 4 weeks. Patients were evaluated at baseline, 3 months and 1 year after treatment using validated visual analog scores. RESULTS: A total of 21 men with a mean age of 47.8 years (range 25 to 67) were analyzed. Mean symptom scores decreased significantly in the actively treated group at 3 months and 1 year (p <0.05), unlike the placebo group, which showed no significant change (p >0.05). Subanalysis of those receiving active treatment showed that the greatest improvement was in pain related symptoms. CONCLUSIONS: The novel use of pelvic floor electromagnetic therapy may be a promising new noninvasive option for chronic pelvic pain syndrome in men.

Adult↗
PubMed2005

Involvement of 5-HT receptors in the regulation of food intake in Siberian hamsters.

The Siberian hamster provides a physiological model for understanding the hypothalamic control of energy metabolism as it undergoes annual photoperiod-regulated cycles of body weight (i.e. fattening in summer, and catabolism of fat stores in winter). As a first step to investigate whether enhanced serotonergic (5-HT) tone might underlie the catabolic processes in short days, we investigated whether serotonergic stimulation can produce catabolic actions in fat hamsters housed in long days. Acute treatment with the serotonin reuptake inhibitor (+/-) fenfluramine (8 mg/kg, i.p.) produced a prolonged, dose-dependent reduction in food intake in both photoperiods. Behavioural observations and radiotelemetry analyses revealed that this anorectic effect of fenfluramine was associated with short-term increases in locomotor activity and in core body temperature. In a subsequent series of studies, hamsters were pretreated with the 5-HT2C receptor antagonist SB242084 (4 mg/kg, i.p.). This 5-HT2C receptor antagonist completely blocked the anorectic actions of fenfluramine, but did not decrease the hyperthermia or hyperlocomotion induced by fenfluramine; thus, the anorectic actions of fenfluramine probably reflect actions via the 5-HT2C receptor. Consistent with these observations, treatment of hamsters with the 5-HT2C receptor agonist VER 3323 (10 mg/kg, i.p.) or the 5-HT1B/2C receptor agonist mCPP (3 mg/kg, i.p.) reduced food intake. The response to manipulation of serotonergic pathways was not affected by the ambient photoperiod in any of these studies. We conclude that the anorectic actions of fenfluramine are not an indirect consequence of serotonergic actions on arousal pathways, and that its actions on feeding in the Siberian hamster are most likely to be mediated by the 5-HT2C receptor.

Aminopyridines↗
PubMed2005

The TGF-beta 1 gene codon 10 polymorphism contributes to the genetic predisposition to nephropathy in Type 1 diabetes.

AIMS: We hypothesize that transforming growth factor-beta (TGF-beta), a multifunctional growth factor which plays a key role in the development of tissue fibrosis, may be involved in the pathophysiology of diabetic nephropathy. Our aim was to examine three polymorphisms within the TGF-beta 1 gene, in codons 10, 25 and 263, for association with nephropathy in Type 1 diabetes. METHODS: We conducted a large case-control study using cases with Type 1 diabetes and clinical nephropathy. Controls were Type 1 diabetic subjects who have been injecting insulin for at least 50 years and have extremely low risk of nephropathy. Genotyping was by polymerase chain reaction with sequence-specific primers. RESULTS: There was a significant difference in the frequency of the TGF-beta 1 codon 10 genotypes in the diabetic nephropathy group (n = 420) when compared with the controls (n = 410, P = 0.007). There were no significant differences when the frequencies of the TGF-beta1 codons 25 and 263 genotypes in the diabetic nephropathy group were compared with the control group. CONCLUSIONS: In our study the TGF-beta 1 codon 10 polymorphism is associated with nephropathy in Type 1 diabetes and variation in this gene may contribute to the genetic predisposition to this complication in Type 1 diabetes.

Adult↗
PubMed2005

Urinary albumin levels in the normal range determine arterial wall thickness in adults with Type 2 diabetes: a FIELD substudy.

AIM: Cardiovascular disease (CVD) rates are substantially higher among patients with Type 2 diabetes than in the general population. The objective of this study was to identify the determinants of carotid intima media thickness (IMT) in patients with Type 2 diabetes. METHODS: We measured the thickness of the intima media layer of the carotid artery, a strong predictor of the risk of future vascular events, in 397 Type 2 diabetic patients drawn from the Fenofibrate Intervention and Event Lowering in Diabetes study, prior to treatment allocation. RESULTS: The mean IMT was 0.78 mm [interquartile range (IQR) 0.23 mm], and the maximum IMT was 1.17 mm (IQR 0.36 mm). By multivariate analysis, age, sex, duration of diabetes, triglycerides, and total cholesterol were independently correlated with IMT, as was urine albumin-creatinine ratio (ACR) (P < 0.001). The effect of ACR on IMT was further examined by tertile. Clinically significant differences in IMT were associated with ACR > 0.65 mg/mmol, approximately one-fifth the standard clinical threshold for microalbuminuria (P < 0.01). Long-term diabetes, independent of other parameters, was associated with a 50% increase in age-related thickening. CONCLUSIONS: IMT in people with Type 2 diabetes is independently and continuously related to urine albumin levels and to the duration of diabetes. These results support previous data linking urine albumin measurements within the normal range with increased ischaemic cardiac mortality in the setting of Type 2 diabetes, and strongly suggest that urine albumin levels within this range should trigger a formal evaluation for CVD.

Aged↗
PubMed2005

Survey of dermatophytes on clinically normal cats in the southeast of England.

OBJECTIVES: To report the incidence of dermatophytes on the hair coat of asymptomatic cats in the southeast of England. Asymptomatic cats are often blamed for transmission of dermatophytes between animals and humans. This study may help to clarify whether cats are responsible for the increase in fungal infections among the human population. METHODS: A total of 169 clinically healthy cats without any dermatological signs were sampled using the Mackenzie brush technique and cultured for dermatophytes. Thirty cats were from a closed colony and 139 were feral or from domestic households in the southeast of England. RESULTS: The incidence of Microsporum canis and Trichophyton mentagrophytes in household and feral cats was 2.16 per cent for each dermatophyte. This survey shows little difference in the isolation rates of M. canis between the southeast and southwest of England, which was reported on in 1994. CLINICAL SIGNIFICANCE: Given the low number of dermatophytes isolated, asymptomatic cats are unlikely to be responsible for the increasing incidence of human infection. Asymptomatic carriers with T. mentagrophytes in the hair coat have not been previously reported and may need to be considered when treating humans with trichophytosis.

Animals↗
PubMed2005

Are we able to comply with the NICE head injury guidelines?

BACKGROUND: An estimated 120,000 patients are admitted to hospital in England and Wales each year for neurological observations following a head injury. The National Institute for Clinical Excellence (NICE) has issued guidelines on the quality and frequency of neurological observations that should be made. OBJECTIVE: Review of frequency and quality of observations in one trauma unit. STUDY DESIGN: Prospective audit of current practice. METHOD: Data on 100 consecutive patients admitted to a trauma unit for neurological observations were audited to monitor the consistency and frequency of neurological observations requested by the admitting doctor. Medical staff had previously been briefed on the recommendations of the NICE head injury guidelines. RESULTS: A detailed evaluation revealed inconsistency and inexplicable gaps in observations. No single set of observations was complete. Sequential regular monitoring was difficult for many reasons, bringing into question the safety and reliability of current practice. CONCLUSIONS: The introduction of the new guidelines which recommend more frequent neurological observations has major staffing implications, where underperformance raises significant clinical governance issues. All hospitals admitting patients with head injuries should have an established protocol based on the NICE guidelines with observations recorded on an appropriately designed data collection form. Trained nursing staff have enormous work and time pressures including direct patient care, ward rounds, drug rounds, administration, management, and responding to emergencies. The development of a competency based training programme for auxiliary nursing staff to undertake neurological observations, including when to report concerns, is one solution to reduce the pressure on trained nursing staff.

Adolescent↗
PubMed2005

The single-dose pharmacokinetics of the novel CCK1 receptor antagonist, dexloxiglumide, are not influenced by age and gender.

OBJECTIVE: The effects of age and gender on the single-dose pharmacokinetics of dexloxiglumide, a selective cholecystokinin (CCK1-subtype) receptor antagonist, were assessed in healthy young and elderly male and female subjects. METHODS: In total, 24 males and 24 females (12 young and 12 elderly subjects per gender group) received a single oral dose of 200 mg dexloxiglumide under fasted conditions. Mean (range) ages were 23.8 (18 - 32) and 71.3 (66 - 88) years for young and elderly subjects, respectively. Analysis of covariance (ANCOVA) with age group and gender as factors and body weight as a covariate was performed on the dexloxiglumide pharmacokinetic parameters of peak plasma concentration (C(max)) and the area under the plasma concentration-time curve (AUC). The p values obtained from ANCOVA were considered for the assessment of age and gender effects. RESULTS: A small (approximately 18%) but statistically significant (p < or = 0.036) increase in the area under the plasma concentration-time curve from 0 to time of last quantifiable concentration (AUC(0-t) and the area under the plasma concentration-time curve from 0 to infinity (AUC(0-infinity)) in elderly compared to young subjects was noted. Given the lack of age effects on the other pharmacokinetic parameters of dexloxiglumide, this limited difference is unlikely to be clinically relevant. Without the adjustment for body weights, female subjects exhibited mean C(max) and AUC values approximately 26% and 36% higher than male subjects; however, these exposure differences did not reach statistical significance (p > 0.05) following ANCOVA analysis with body weight as a covariate. Likewise, there were no statistically significant differences (p > 0.05) observed for any other pharmacokinetic parameters between young and elderly and between male and female groups. CONCLUSIONS: Dose adjustments based on age and gender are not necessary. Dexloxiglumide administration was safe and well tolerated in these subjects.

Adolescent↗