The intubating laryngeal mask and laser surgery.
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Anesthesia↗
Biomedical subjects
A Patel
Publications and source records attributed to A Patel.
Primary coronary angioplasty compared with intravenous thrombolytic therapy for acute myocardial infarction: six-month follow up and analysis of individual patient data from randomized trials.
BACKGROUND: Overviews of trials suggest that percutaneous transluminal coronary angioplasty (PTCA) may be more effective than thrombolysis. However, whether these effects are sustained beyond hospital discharge, and the extent to which the results are applicable to a broad cross section of patients and the wider community are unknown. We compared the effectiveness of primary PTCA and thrombolysis in acute myocardial infarction during a 6-month follow-up period. METHODS: Detailed individual patient data were collected from randomized trials commenced from 1989 to 1996 that compared primary PTCA with thrombolysis. Data were combined to produce estimates of relative reduction in events at 30 days and 6 months for the group and for predefined clinical subgroups. Treatment effects were also assessed in relation to several study-related factors. RESULTS: Eleven trials were identified. The mortality rate at 30 days was 4.3% for 1348 patients randomized to undergo PTCA, and 6.9% for 1377 patients assigned to thrombolytic therapy (relative risk [RR] 0.62, 95% CI 0.44-0.86, P =.004). At 6 months, the mortality rate was 6.2% for PTCA and 8.2% for thrombolysis (RR 0.73, 95% CI 0.55-0.98, P =.04). Combined death and reinfarction rates at 30 days were 7.0% for PTCA and 12.9% for thrombolysis, with a sustained effect at 6 months (RR 0.60, 95% CI 0.48-0.75, P <.0001). The risk of hemorrhagic stroke at 30 days was lower in the PTCA group (RR 0.06, 95% CI 0.0-0.50, P =.009). The relative treatment effect did not vary across clinically important subgroups, but the absolute benefit varied according to baseline risk. The relative treatment effect varied across the trials and according to the thrombolytic comparator used, the delay in performing PTCA, and the recruitment rate. CONCLUSION: In the context of these trials, primary PTCA was more effective than thrombolytic therapy in reducing death, reinfarction, and stroke, with the greatest absolute benefit in patients who were at the highest risk. These benefits appear to be sustained for 6 months. The effect of treatment varied significantly across the trials, and this raises issues about how widely the results can be applied.
Aged↗
Cholesterol, coronary heart disease, and stroke in the Asia Pacific region.
BACKGROUND: Cholesterol levels in many Asian countries are rising. Predictions of the likely effects of this on the incidence of cardiovascular diseases have mostly relied on data from Western populations. Whether the associations between total cholesterol and cardiovascular diseases are similar in Asia is not established. METHODS: The Asia Pacific Cohort Studies Collaboration (APCSC) is an individual-participant data meta-analysis of prospective studies from the Asia-Pacific region. Cox models were applied to the combined data from 29 cohorts to estimate the region-, sex-, and age-specific hazard ratios of major cardiovascular diseases by the fifths of total cholesterol. RESULTS: At baseline, the age/sex-adjusted mean value of total cholesterol was higher in Australia and New Zealand (ANZ) (5.52 +/- 1.05 mmol/l) than in Asia (4.87 +/- 1.05 mmol/l). During 2 million person-years of follow-up among 352 033 individuals, 4841 cardiovascular deaths were recorded. The association of total cholesterol with coronary heart disease and stroke was similar in Asian and ANZ cohorts. Overall, each 1-mmol/l higher level of total cholesterol was associated with 35% (95% CI: 26-44%) increased risk of coronary death, 25% (95% CI: 13-40%) increased risk of fatal or non-fatal ischaemic stroke, and 20% (95% CI: 8-30%) decreased risk of fatal haemorrhagic stroke. CONCLUSIONS: In both Asian and non-Asian populations in the Asia-Pacific region, total cholesterol is similarly strongly associated with the risk of CHD and ischaemic, but not haemorrhagic, stroke. Rising population-wide levels of cholesterol would be expected to contribute to a substantial increase in the overall burden of cardiovascular diseases in this region.
Adult↗
Characterization of a new solvent-responsive gene locus in Pseudomonas putida F1 and its functionalization as a versatile biosensor.
A new gene cluster, designated sepABC and a divergently transcribed sepR, was found downstream of the two-component todST phosphorelay system that regulates toluene degradation (the tod pathway) in Pseudomonas putida F1 (PpF1). The deduced amino acid sequences encoded by sepABC show a high homology to bacterial proteins known to be involved in solvent efflux or multidrug pumps. SepA, SepB and SepC are referred to be periplasmic, inner membrane and outer membrane efflux proteins respectively. Effects on growth of various PpF1 mutants compared to that of the wild type in the presence of toluene indicated a possible protective role of the solvent efflux system in a solvent-stressed environment. Growth tests with the complemented mutants confirmed the involvement of the Sep proteins in conferring solvent tolerance. The sepR gene encodes a 260-residue polypeptide that is a member of the E. coli IclR repressor protein family. The repressor role of SepR was established by conducting tests with a sep-lacZ transcriptional fusion in Escherichia coli and PpF1, expression of SepR as a maltose-binding fusion protein in a DNA binding assay, and mRNA analysis. Southern hybridization experiments and analysis of the P. putida KT2440 genome sequence indicated that sepR is a relatively rare commodity compared to homologues of the sepABC genes. We developed a whole-cell bioluminescent biosensor, PpF1G4, which contains a chromosomally based sep-lux transcriptional fusion. The biosensor showed significant induction of the sepABC genes by a wide variety of aromatic molecules, including benzene, toluene, ethylbenzene, and all three isomers of xylene (BTEX), naphthalene, and complex mixtures of aliphatic and aromatic hydrocarbons. PpF1G4 represents a second-generation biosensor that is not based on a catabolic promoter but is nonetheless inducible by aromatic pollutants and moreover functional under nutrient-rich conditions.
Bacterial Proteins↗
Clinical criteria and the appropriate use of transthoracic echocardiography for the exclusion of infective endocarditis.
BACKGROUND: Clinical guidelines currently suggest that transthoracic echocardiography (TTE) be carried out in all patients with suspected endocarditis, but the use of TTE where there is a low probability of infective endocarditis has a poor diagnostic yield. This screening approach may no longer be appropriate. OBJECTIVE: To examine whether clinical criteria might aid decision making with respect to the use of TTE in possible endocarditis. DESIGN: A retrospective review of patient records. SETTING: Cardiology department of a tertiary referral centre. PATIENTS: 500 consecutive hospital inpatients referred for TTE to exclude endocarditis. MAIN OUTCOME MEASURES: Evidence of endocardial vegetations on TTE and the presence of predetermined clinical criteria that may predispose to, or be suggestive of, endocarditis. RESULTS: Evidence of infective endocarditis was detected on echocardiography in 43 of the 500 patients (8.6%). In 239 patients (48%), vegetations and certain prespecified clinical criteria were both absent. These criteria were: vasculitic/embolic phenomena; the presence of central venous access; a recent history of injected drug use; presence of a prosthetic valve; and positive blood cultures. The collective absence of these five criteria indicated a zero probability of TTE showing evidence of endocarditis. CONCLUSIONS: The use of simple clinical criteria during the decision making process may avoid many unnecessary TTE examinations in hospital inpatients with a low probability of endocarditis.
Analysis of Variance↗
A new technique for the management of inaccessible anterior glottic lesions.
We describe a new technique for removing anterior vocal fold lesions, which cannot be visualized with conventional suspension laryngoscopy. These situations are rare and the only alternative surgeons have had previously is an open laryngeal procedure. The technique we describe involves the use of a laryngeal mask airway (LMA), a flexible bronchoscope with biopsy channel, a 400 microm laser fibre and KTP/532 nm laser. This method was used to treat two patients in whom conventional suspension laryngoscopy had previously been attempted and abandoned.
Adult↗
Synovial dendritic cells in juvenile idiopathic arthritis (JIA) express receptor activator of NF-kappaB (RANK).
OBJECTIVES: To analyse the expression of receptor activator of NF-kappaB (RANK) and RANK ligand (RANKL) in the joints of children with juvenile idiopathic arthritis (JIA), to characterize the phenotype of RANK(+) cells and to test the hypothesis that some RANK(+) cells are of the dendritic type. METHODS: Paired samples of peripheral blood mononuclear cells (PBMC) and synovial fluid mononuclear cells (SFMC) from children with oligoarticular (n=14) or polyarticular (n=4) JIA and PBMC from 10 control subjects were studied for expression of RANK, RANKL and dendritic cell-specific ICAM (intercellular adhesion molecule)-grabbing non-integrin (DC-SIGN) by the reverse transcriptase-polymerase chain reaction and three-colour flow cytometry. Expression of DC-SIGN and RANK was followed after 1 week of culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). RESULTS: mRNA for RANK was detected in both adherent cells and T cells from PBMC and SFMC of patients with JIA and in control PBMC, while mRNA for RANKL was detectable in the T-cell fraction from JIA patients but not in that from controls. By flow cytometry, a large number of RANK(+) cells were detected in the joint; these cells had the phenotype HLA-DR(hi)CD86(hi) CD11c(+) and expressed low levels of DC-SIGN. CONCLUSIONS: There is increased expression of RANKL and RANK in the juvenile arthritic joint. RANK is expressed on a population of cells with features of dendritic cells. RANK/RANKL interactions may contribute to the survival of inflammatory cells within the joint, as well as to erosions and osteoporosis in juvenile arthritis.
Adult↗
Investigation into the potential pathogenicity of Staphylococcus felis in a cat.
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Amoxicillin-Potassium Clavulanate Combination↗
Volumetric structural magnetic resonance imaging (MRI) of the rat hippocampus following kainic acid (KA) treatment.
An in vivo MRI study employing a high field (7T) magnet and a T1- and T2-weighted imaging sequence with subsequent histopathological evaluations was undertaken to develop and evaluate MRI-based volumetric measurements in the rat. The brain structures considered were the hippocampus, the cingulate cortex, the retrosplenial granular cortex and the ventricles. Control (n=3) and kainic acid (KA; n=4) treated rats were scanned 10 days following the manifestation of stage four seizures. The MRI images exhibited anatomical details (125 microm in-plane resolution) that enabled volumetric analysis with high intra-rater reliability. Volumetric analysis revealed that KA-treated rats had significantly smaller hippocampi, and a significant increase in ventricular size. The cingulate cortex and the retrosplenial granular cortex did not differ in volume between the two groups. The histological observations supported the MRI data showing neuronal loss and neuronal degeneration in CA1 and CA3 of the hippocampus, which was accompanied by strong microglia activation. These data demonstrate a reliable and valid method for the measurement of the rat hippocampus in vivo using MRI with a high field magnet, thereby providing a useful tool for future studies of rodent models of neuro-degenerative diseases.
Animals↗
Varicose veins possess greater quantities of MMP-1 than normal veins and demonstrate regional variation in MMP-1 and MMP-13.
BACKGROUND: Studies have reported that structural proteins such as elastin and collagen are decreased in varicose veins compared to normal controls. We hypothesized that the changes observed in varicose vein wall composition may be related to alterations in extracellular matrix remodeling proteins, such as the matrix metalloproteases and serine proteases. In addition we hypothesized that there may be regional variation in the expression of these enzymes within the leg. PATIENTS AND MATERIALS: One-centimeter segments of the proximal and distal greater saphenous vein (GSV) were obtained from patients undergoing ligation and stripping for venous insufficiency (vv) (n = 15) or GSV harvest in conjunction with coronary artery bypass grafting (CABG) (n = 7). All vv patients had incompetence of the GSV by color flow duplex. Vein specimens were examined for MMP-1, 3, and 13, tryptase, and GAPDH mRNA using semiquantitative RT-PCR analysis. Quantification of MMP-1 and 13 (active/latent forms) and tryptase was performed using Western blot analysis. Western blots were analyzed using scanning densitometry and standardized to normal controls and values expressed as the median densitometric index (D.I.). Nonparametric statistical methods (Wilcoxan signed rank test and Mann-Whitney U test) were used for analysis. RESULTS: We were able to amplify MMP-1, MMP-13, and tryptase mRNA from both proximal and distal segments of all greater saphenous veins studied. MMP-3 mRNA, however, was not found in either segment of any of the veins examined. A semiquantitative analysis of RT-PCR products comparing the ratio of MMP-1, MMP-13, or tryptase mRNA to GAPDH mRNA showed no difference between cases and controls nor proximal vs distal vein segments. Western blot analysis revealed larger quantities of MMP-1 in varicose veins than in nondiseased veins from CABG patients (48.0 +/- 36.7 D.I. vs 12.5 +/- 6.8 D.I., P = 0.036). Investigation into the regional variation of proteases revealed lower amounts of MMP-1 in distal than in proximal vein segments (37.9 +/- 35.0 D.I. vs 44.1 +/- 41.6 D.I., P = 0.01). Similarly, we found significantly less MMP-13 in distal segments of varicose veins than in proximal segments (152.8 +/- 130.0 D.I. vs 206.7 +/- 173.3 D.I., P = 0.006). CONCLUSIONS: This study found that MMP-1 protein is increased in varicose veins when compared to controls despite no differences in mRNA expression. In addition we found that there is regional variation of MMP-1 and MMP-13 in diseased varicose veins. Lower leg veins have significantly reduced amounts of these proteolytic enzymes when compared to veins of the upper thigh. These data suggest that posttranscriptional regulatory controls could be responsible for the observed differences.
Adult↗
Thyroid carcinomas that express telomerase follow a more aggressive clinical course in children and adolescents.
With each cell division, DNA is lost from the telomeres, limiting the number of divisions, and leading to senescence. Malignant tumors maintain immortality by expressing a specific DNA repair enzyme, telomerase, that replaces this DNA. We hypothesized that tumors which express telomerase would have the highest recurrence risk and we tested this by determining telomerase expression in 27 papillary thyroid carcinomas (PTC), 5 follicular thyroid carcinomas (FTC) and 13 benign thyroid lesions from children and adolescents. Patients were 6-21 yr of age (mean+/-SE=16.6+/-4.1 yr) and followed from 0-14.1 yr (mean+/-SE=4.71+/-3.5 yr). Original tumors were sectioned, and immunostained for telomerase. Telomerase-specific staining was determined by two independent, blind examiners and graded from absent (Grade 0) to intense (Grade 3). Telomerase was detected in a similar majority of benign (11/13, 85%) and malignant tumors (24/32, 75%). However, the intensity of telomerase expression was greater among FTC (mean+/-SE=2.4+/-0.5 relative intensity) followed by PTC (mean+/-SE=1.9+/-1.0 relative intensity) and benign tumors (mean+/-SE=1.8+/-1.0 relative intensity). Autoimmune lesions had lower telomerase expression (mean+/-SE=1.25+/-0.5 relative intensity) compared to FTC (p=0.01), PTC (p=0.06) and benign lesions (p=0.15). Among PTC, 19 (70%) expressed telomerase, and 8 (30%) did not. Direct invasion (no.=4, 21%), distant metastasis (no.=2, 10%) and recurrence (no.=7, 37%) developed exclusively in PTC that expressed telomerase (p=0.02). Disease-free survival was also shorter for PTC that expressed telomerase (p=0.06). Recurrence developed in 1/2 (50%) FTC that expressed telomerase. We conclude that childhood thyroid cancers which express telomerase have an increased risk of tissue invasion, metastasis, and recurrence.
Adenocarcinoma, Follicular↗
Matrix metalloproteinase (MMP) expression by differentiated thyroid carcinoma of children and adolescents.
The factor(s) that control metastasis of thyroid carcinoma are unknown, but the matrix metalloproteinases (MMPs) are excellent candidates. MMP-1, membrane-type-1 MMP (MT1-MMP), and tissue inhibitor of MMP-1 (TIMP-1) have all been implicated, but the site of production and importance are disputed. In vitro, normal thyroid cells secrete TIMP-1, while thyroid cancer cells secrete TIMP-1 and MMP-1. However, previous pathological studies identified MMP-1 and TIMP-1 only in the stroma surrounding thyroid carcinoma. These data suggest that thyroid carcinoma or tumor-associated inflammatory cells might secrete a factor(s) which stimulates MMP-1 or TIMP-1 expression by surrounding tissues. We hypothesized that MMP-1, MT1-MMP, and TIMP-1 would be directly expressed by thyroid carcinoma and might promote invasion or metastasis. We used immunohistochemistry to determine the expression of MMP-1, MT1-MMP, and TIMP-1 in 32 papillary thyroid carcinoma (PTC), 10 follicular thyroid carcinoma (FTC) and 13 benign thyroid lesions from children and adolescents. The intensity of staining was graded from absent (grade 0) to intense (grade 3). Average MMP-1 expression (mean relative intensity units+/-SE) was significantly greater among PTC (1.97+/-0.15; p=0.004) and FTC (2.2+/-0.25; p=0.006) compared to benign lesions (1.30+/-0.15); but there was no relationship between MMP-1 expression and invasion, metastasis, or recurrence. Expression of MT1-MMP and TIMP-1 was similar for benign and malignant lesions; but recurrent PTC expressed lower levels of TIMP-1 when compared to non-recurrent PTC (p=0.049). Only the expression of TIMP-1 correlated with the presence of tumor-associated lymphocytes (r=0.35, p=0.032). We conclude that MMP-1, MT1-MMP and TIMP-1 are all expressed by thyroid carcinoma and could be important in promoting recurrence.
Adenocarcinoma, Follicular↗
Nitrotyrosine, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) are increased in thyroid tumors from children and adolescents.
Nitric oxide (NO) is a reactive cell signal that controls vascular tone and is generated by inducible (iNOS), endothelial (eNOS) and neuronal (nNOS) NO synthase (NOS). We hypothesized that NO could be important for growth of thyroid tumors and tested this hypothesis, by staining 41 papillary thyroid carcinoma (PTC), 9 follicular thyroid carcinoma (FTC), and 15 benign thyroid lesions for iNOS, eNOS and nitrotyrosine (N-TYR). Staining intensity was determined by 2 blinded, independent examiners, and quantified from grade 1 (absent) to grade 4 (intense). Average N-TYR staining of benign adenomas (2.5+/-0.42, p=0.009), PTC (3.10+/-0.12, p=0.001), FTC (2.44+/-0.30, p=0.001), and autoimmune lesions (3.25+/-0.48, p=0.019) were greater than that of multinodular goiter (1.0 for all 3) and surrounding normal thyroid (1.1+/-0.1). Average iNOS staining of benign adenomas (2.6+/-0.37), PTC (2.7+/-0.16), FTC (2.4+/-0.26) and autoimmune lesions (3.5+/-0.29) were all greater than that of surrounding normal thyroid (1.1+/-0.1, p<0.008), but there were too few multinodular goiters to achieve a significant difference (no.=2, 3.0+/-1.0). Average eNOS staining of benign adenomas (2.9+/-0.40), multinodular goiters (3.5+/-0.5), PTC (3.24+/-0.18), FTC (3.5+/-0.50), and autoimmune lesions (2.8+/-0.6) were also greater than that of surrounding normal thyroid (mean=1.4+/-0.2, p<0.001). N-TYR staining correlated with that of vascular endothelial growth factor (VEGF, r=0.36, p=0.007) and the number of lymphocytes/high power field (r=0.39, p=0.004). Recurrent disease developed only from carcinoma with moderate-intense N-TYR staining, but there were too few recurrent tumors to achieve statistical significance (p=0.08). We conclude that NO is produced by benign adenomas, PTC and FTC suggesting that NO could be important in vascularization of thyroid tumors and autoimmune thyroid diseases.
Adenocarcinoma, Follicular↗
Heavy users of acute psychiatric beds: randomized controlled trial of enhanced community management in an outer London borough.
BACKGROUND: Heavy users of psychiatric services, often defined as the population that uses the most beds, consume a large part of the resources used by the whole service, despite being relatively small in number. Any intervention that reduces heavy use is therefore likely to lead to significant savings, and enhancement of standard care using a form of intensive case management akin to assertive community treatment was thought to be a pragmatic strategy for testing in this group. METHODS: The effectiveness of enhanced community management (ECM) was compared with standard care alone in heavy users, who represented the 10% of patients with the highest number of hospital admissions and occupied bed days over the previous 6.5 years in an outer London borough. One hundred and ninety-three patients were randomly assigned to ECM or standard care and their use of services was determined after 1 and 2 years, with assessments of costs, clinical symptoms, needs, and social function made before entry into the study and after 1 and 2 years. RESULTS: Despite a 24 fold increase in community contacts in the study group, there were no significant differences between the two groups in any of the main outcome measures. Small savings on in-patient and day-hospital service costs were counterbalanced by the increased costs of outpatient and community care for the subjects assigned to ECM. Clinical outcome data derived from interviews in two-thirds of the subjects were similar in both groups. CONCLUSIONS: Providing additional intensive community focused care to a group of heavy users of psychiatric in-patient services in an outer London borough does not lead to any important clinical gains or reduced costs of psychiatric care.
Adolescent↗
Coaxial breathing system outer tube occlusion: what goes in must come out.
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Aged↗
Management of mobile laryngeal tumours.
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Anesthesia, Inhalation↗
Clinical characteristics and outcome of patients with early (<2 h), intermediate (2-4 h) and late (>4 h) presentation treated by primary coronary angioplasty or thrombolytic therapy for acute myocardial infarction.
AIMS: We examined the clinical characteristics and outcome of patients with early (<2 h), intermediate (2-4 h) and late (>4 h) presentation treated by primary angioplasty or thrombolytic therapy for acute myocardial infarction. METHODS AND RESULTS: We studied 2635 patients enrolled in 10 randomized trials of primary angioplasty (n=1302) vs thrombolytic therapy (n=1333) in acute myocardial infarction, and baseline characteristics of the two groups were comparable. Increase in presentation delay is associated with older age, female gender, diabetes and an increased heart rate. We classified the patients according to the time delay from symptom onset to presentation into three categories: early presentation (<2 h), intermediate presentation (2-4 h), and late presentation (>or=4 h). At 30 days the combined rate of death, non-fatal reinfarction and stroke in patients presenting early was 5.8% in the angioplasty group vs 12.5% in the thrombolysis group, in patients with intermediate presentation, 8.6% vs 14.2%, respectively, and in patients presenting late 7.7% vs 19.4%, respectively. With increasing time from symptom onset to presentation, all major adverse cardiac event rates show a trend to a larger increase in the thrombolysis group compared to the angioplasty group, both at 30 days and at 6 months after the acute event. CONCLUSIONS: Major adverse cardiac event rates are lower after angioplasty compared to thrombolysis, irrespective of time to presentation. With increasing time to presentation major adverse cardiac event rates increase after thrombolysis but appear to remain relatively stable after angioplasty.
Adult↗
Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability.
BACKGROUND: Codeine analgesia is wholly or mostly due to its metabolism to morphine by the cytochrome P450 enzyme CYP2D6, which shows significant genetic variation in activity. The aims of this study were to investigate genotype, phenotype and morphine production from codeine in children undergoing adenotonsillectomy, and to compare analgesia from codeine or morphine combined with diclofenac. METHODS: Ninety-six children received either codeine 1.5 mg kg(-1) or morphine 0.15 mg kg(-1) in a randomized, double-blind design. Genetic analysis was performed and plasma morphine concentrations at 1 h were determined. Postoperative analgesia and side-effects were recorded. RESULTS: Forty-seven per cent of children had genotypes associated with reduced enzyme activity. Mean (SD) morphine concentrations were significantly lower (P<0.001) after codeine [4.5 (0.3) ng ml(-1)] than after morphine [24.7 (1.5) ng ml(-1)], and morphine and its metabolites were not detected in 36% of children given codeine. There was a significant relationship between phenotype and plasma morphine (P=0.02). More children required rescue analgesia after codeine at both 2 (P<0.05) and 4 h after administration (P<0.01). Fifty-six per cent of children vomited after morphine and 29% after codeine (P<0.01). Neither phenotype nor morphine concentration was correlated with either pain score or the need for rescue analgesia (r=-0.21, 95% confidence interval -0.4, -0.01). CONCLUSIONS: Reduced ability for codeine metabolism may be more common than previously reported. Plasma morphine concentration 1 h after codeine is very low, and related to phenotype. Codeine analgesia is less reliable than morphine, but was not well correlated with either phenotype or plasma morphine in this study.
Analgesia↗