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Biomedical subjects

D Patel

Publications and source records attributed to D Patel.

At least 19 recordsLinked to original sources

Spinal fusion surgery in children with non-idiopathic scoliosis: is there a need for routine postoperative ventilation?

BACKGROUND: The perioperative management of children with non-idiopathic scoliosis undergoing spinal deformity surgery has not been standardized and the current practice is to routinely ventilate these patients in the postoperative period. This study reports the experience from a single institution and evaluates the need and reasons for postoperative ventilation. Details of ventilated patients are presented. METHODS: All patients undergoing spinal fusion surgery for non-idiopathic scoliosis were recorded prospectively (2003-4). Patients were anaesthetized according to a standardized technique. Physical characteristics, cardiopulmonary function, intraoperative blood loss and fluid requirement, postoperative need for ventilation and all perioperative adverse events were recorded on a computer database. RESULTS: A total of 76.2% of patients were safely extubated at the end of surgery without any further complications or need for re-ventilation; 23.8% of patients required postoperative ventilation with half of the cases being planned before operation and 40% of all patients with Duchenne muscular dystrophy (DMD) required postoperative ventilation. There were no specific factors that could predict the need for postoperative ventilation, although an increased tendency for children with DMD and those with a preoperative forced vital capacity <30% towards requiring postoperative ventilation was observed. CONCLUSIONS: Early extubation can be safely performed after spinal deformity surgery for non-idiopathic scoliosis. The use of short-acting anaesthetics, drugs to reduce blood loss, experienced spinal anaesthetists and the availability of intensive care support are all essential for a good outcome in patients with neuromuscular disease and cardiopulmonary co-morbidity.

Adolescent↗

High-brightness injection-seeded soft-x-ray-laser amplifier using a solid target.

We demonstrate the generation of an intense soft-x-ray-laser beam by saturated amplification of high harmonic seed pulses in a dense transient collisional soft-x-ray-laser plasma amplifier created by heating a titanium target. Amplification in the 32.6 nm line of Ne-like Ti generates laser pulses of subpicosecond duration that are measured to approach full spatial coherence. The peak spectral brightness is estimated to be approximately 2 x 10(26) photons/(s mm(2) mrad(2) 0.01% bandwidth). The scheme is scalable to produce extremely bright lasers at very short wavelengths with full temporal and spatial coherence.

Journal Article↗

Induction of tetraploidy through loss of p53 and upregulation of Plk1 by human papillomavirus type-16 E6.

Cancer cells are insensitive to many signals that inhibit growth of untransformed cells. Here, we show that primary human epithelial cells expressing human papillomavirus (HPV) type-16 E6/E7 bypass arrest caused by the DNA-damaging drug adriamycin and become tetraploid. To determine the contribution of E6 in the context of E7 to the resistance of arrest and induction of tetraploidy, we used an E6 mutant unable to degrade p53 or RNAi targeting p53 for knockdown. The E6 mutant fails to generate tetraploidy; however, the presence of E7 is sufficient to bypass arrest while the p53 RNAi permits both arrest insensitivity and tetraploidy. We published previously that polo-like kinase 1 (Plk1) is upregulated in E6/E7-expressing cells. We observe here that abnormal expression of Plk1 protein correlates with tetraploidy. Using the p53 binding-defective mutant of E6 and p53 RNAi, we show that p53 represses Plk1, suggesting that loss of p53 results in tetraploidy through upregulation of Plk1. Consistent with this hypothesis, overexpression of Plk1 in cells generates tetraploidy but does not confer resistance to arrest. These results support a model for transformation caused by HPV-16 where bypass of arrest and tetraploidy are separable consequences of p53 loss with Plk1 required only for the latter effect.

Cell Cycle Proteins↗

The multidisciplinary team meeting improves staging accuracy and treatment selection for gastro-esophageal cancer.

The object of this article is to assess current staging accuracies for individual modalities and to investigate the influence of the multidisciplinary team (MDT) on clinical staging accuracies and treatment selection for patients with gastro-esophageal cancer. Patients newly diagnosed with gastric or esophageal cancer and who were deemed suitable for surgical resection by the MDT were studied. Patients were staged with a combination of computerized tomography (CT), endoscopic ultrasound (EUS) and laparoscopic ultrasound (LUS). Additionally, the MDT determined an overall clinical stage for each patient after discussion at the MDT meeting. Treatments were selected according to this final clinical stage. Final histopathological staging (pTNM) was available for all patients and was used as the gold standard for determining staging accuracy. Suitability of treatment selection was assessed once final pTNM was available. One hundred and eighteen patients were studied. Endoscopic ultrasound was the most accurate individual staging modality for the loco-regional assessment of esophageal tumors (T stage accuracy 78%, N stage accuracy 70%). Laparoscopic ultrasound was the most accurate modality in T staging of gastric cancers (91%). The MDT stage was more accurate than each individual staging modality for T and N staging for both gastric and esophageal cancers (accuracy range: 88-89%) and was better for the assessment of nodal disease than each individual modality (CT P < 0.001, EUS P < 0.01, LUS P < 0.01). Overall staging accuracy as determined at the MDT meeting was increased and resulted in only 2/118 (2%) patients being under-treated. The MDT significantly improves staging accuracy for gastro-esophageal cancer and ensures that correct management decisions are made for the highest number of individual patients.

Adenocarcinoma↗

Homologous blood transfusion is not required in surgery for adolescent idiopathic scoliosis.

We studied 70 consecutive patients with adolescent idiopathic scoliosis who underwent corrective surgery. They were divided into two groups. In the study group of 38 patients one or more modern blood-conservation measures was used peri-operatively. The 32 patients in the control group did not have these measures. Both groups were similar in regard to age, body-weight, the number of levels fused and the type of surgery. Only two patients in the study group were transfused with homologous blood and these transfusions were 'off-protocol'. Wastage of autologous pre-donated units was minimal (6 of 83 units). By contrast, all patients in the control group were transfused with homologous blood. In the study group there was a significant decrease (p = 0.005) in the estimated blood loss when all the blood-conservation methods were used. The use of blood-conservation measures, the lowering of the haemoglobin trigger for transfusion and the education of the entire team involved in the care of the patient can prevent the need for homologous blood transfusion in patients undergoing surgery for adolescent idiopathic scoliosis.

Adolescent↗

Direct sequence comparison of two divergent class I MHC natural killer cell receptor haplotypes.

The murine Ly49 gene family encoding natural killer cell receptors for class I MHC is an example of a rapidly evolving cluster of immune response genes. Determining the genomic sequence of the 129S6/SvEvTac (129S6) Ly49 cluster and comparing it to the known sequence of the C57BL/6 (B6) region provided insight into the mechanisms of Ly49 gene evolution. 129S6 contains 20 Ly49, many of which are pseudogenes and 40% of the genes have no counterpart in the B6 genome. The difference in gene content between these two strains is primarily the result of distinct patterns of gene duplication. Phylogenetic analyses of individual exons showed that Ly49 genes form distinct sub-families and an ancestral haplotype can be surmised. Dotplot analysis supports limited allelism in the two haplotypes; however, large regions of variation punctuate these islands of co-linearity. These variable regions contain a high concentration of repetitive elements that are predicted to contribute to the dynamic evolution of this cluster. The extreme variation in Ly49 haplotype content between mouse strains provides a genetic explanation for the documented differences in natural killer cell phenotype, and also indicates that differences in natural killer cell function observed between B6 and 129-derived gene-targeted mice should be interpreted with caution.

Amino Acid Sequence↗

The role of orthodontics and oral and maxillofacial surgery in the management of obstructive sleep apnoea - a single case report.

Obstructive sleep apnoea (OSA) is a potentially fatal breathing disorder, yet is widely under-diagnosed. It is a multi-factorial condition associated with high morbidity, a degree of mortality and is associated with an increase risk of car crashes. A case is presented which demonstrates the inter-disciplinary approach to this condition and the successful treatment through mandibular advancement by orthodontic means followed by orthognathic surgery. The experience of this patient illustrates the importance of the disciplines of orthodontics and oral and maxillofacial surgery in the multi-disciplinary management of these patients.

Continuous Positive Airway Pressure↗

Effects of mutations in the N terminal region of the yeast G protein alpha-subunit Gpa1p on signaling by pheromone receptors.

The sites and modes of interaction between G protein-coupled receptors and their cognate heterotrimeric G proteins remain poorly defined. The C-terminus of the Galpha subunit is the best established site of contact of G proteins with receptors, but structural analyses and crosslinking studies suggest the possibility of interactions at the N-terminus of Galpha as well. We screened for mutations in the N-terminal region of the Galpha subunit encoded by the yeast GPA1 gene that specifically affect the ability of the G protein to be activated by the yeast alpha-mating factor receptor. The screen led to identification of substitutions of glutamine or proline for Leu18 of Gpa1p that reduce the response to the pheromones alpha-factor and a-factor without affecting cellular levels of the subunit or its ability to interact with beta and gamma subunits. The mutations do not appear to affect the intrinsic ability of the G protein to be converted to the activated state. The low yield of different mutations with this phenotype indicates either that the N-terminal segment of the yeast Galpha subunit does not undergo extensive interactions with the alpha-factor receptor, or that this region can not be altered without detrimental effects upon the formation of G protein trimers.

Alleles↗

The rationale behind autologous autoimmune hematopoietic stem cell transplant conditioning regimens: concerns over the use of total-body irradiation in systemic sclerosis.

Hematopoietic stem cell transplantation (HSCT) is becoming an increasingly recognized indication for treatment of autoimmune diseases and severe immune-mediated disorders. However, multicenter registry data have demonstrated higher than anticipated early toxicity, approximately 10% for autoimmune diseases in general, and 20-27% for diffuse systemic sclerosis (scleroderma). If uncorrected, this high treatment-related mortality will hinder development of stem cell therapy for immune-mediated diseases. In order to develop safer regimens, we address some pitfalls and concepts involved in design and selection of conditioning regimens for autoimmune diseases in general, and because it is associated with the highest regimen-related toxicity, scleroderma in specific.

Autoimmune Diseases↗

Analysis of full-length HIV type 1 env genes indicates differences between the virus infecting T cells and dendritic cells in peripheral blood of infected patients.

Dendritic cells (DC) are targets for HIV-1 infection and may harbor distinct populations of virus variants. To test this hypothesis full length env genes have been amplified and sequenced from DC and T cells purified from the blood of five symptomatic HIV-1-infected patients. For three of the patients, showing slow and slow/standard disease progression, distinct subsets of HIV variants infected DC and T cells, and the diversity of the DC-derived env genes was less than that observed in T cells. Amino acid substitutions differentiating DC and T cell variants were dispersed throughout the length of the glycoproteins and were patient/HIV-1 strain specific. However, the V1 and V2 domains of T cell-derived clones were generally shorter than those from DC. These findings suggest that there may be distinct populations of HIV-1 variants infecting blood DC and T cells in patients showing slow and slow/standard disease progression.

Adult↗

Celiac disease.

Explore the source record for details and available documents.

Adult↗

Alpha-substituted hydroxamic acids as novel bacterial deformylase inhibitor-based antibacterial agents.

We report the synthesis and biological activity of analogues of VRC3375 (N-hydroxy-3-R-butyl-3-[(2-S-(tert-butoxycarbonyl)-pyrrolidin-1-ylcarbonyl]propionamide), an orally active peptide deformylase inhibitor. This study explores the structure-activity relationship of various chelator groups, alpha substituents, P(2)' and P(3)' substituents in order to achieve optimal antibacterial activity with minimal toxicity liability.

Amidohydrolases↗

CT-guided lung biopsy: factors influencing diagnostic yield and complication rate.

AIM: To determine factors influencing diagnostic yield in computed tomography (CT)-guided biopsy of lung lesions. MATERIALS AND METHODS: One hundred and ninety-five consecutive CT-guided lung biopsies were performed in 182 patients between August 1995 and September 2000 and either fine-needle aspirate samples for cytology or core biopsy samples for histology were collected. Procedures were divided into a diagnostic group (true-positive and true-negative results) and a non-diagnostic group (false-positive and false-negative results) and the factors affecting diagnostic accuracy assessed. RESULTS: One hundred and fifty-six lesions (86%) were malignant, and 26 (14%) were benign. More than one biopsy was performed for 12 lesions. One hundred and thirty-two biopsies were true-positive, 27 true-negative and 36 false-negative. No false-positive results occurred in the study. Overall diagnostic accuracy was 81.5%. Significantly more core biopsies than fine-needle aspirates were diagnostic: 93 versus 78% (p<0.005). No difference was found in frequency of pneumothorax between these two groups. There was a difference in the average depth from the pleural surface of lesions in the diagnostic and non-diagnostic groups, but this did not attain statistical significance: 9.8 versus 17.2 mm (p=0.054). CONCLUSION: In this study CT-guided lung biopsy core biopsy was a more accurate method of tissue sampling than fine-needle aspiration, and was not associated with an excess of complications.

Adult↗

Plasma paracetamol concentrations after different doses of rectal paracetamol in older children A comparison of 1 g vs. 40 mg x kg(-1).

We compared the plasma paracetamol levels attained after the administration of different doses of rectal paracetamol in healthy children to see if they attained therapeutic levels (> 10 microg x ml(-1)). We recruited 24 children (ASA I-III) over 25 kg undergoing elective surgery. They were randomly assigned to receive rectal paracetamol at a dose of 1 g or 40 mg x kg(-1). Blood samples were taken for analysis at 2, 3, 4 and 5 h post dose. Most children in the 1 g group failed to attain therapeutic plasma levels, whereas those in the 40 mg kg(-1) group did achieve therapeutic levels (mean maximum concentration = 7.8 vs. 15.9 microg x ml(-1), p = 0.009).

Acetaminophen↗

The current status of sports medicine training in United States internal medicine residency programmes.

OBJECTIVE: To determine the general status of sports medicine training in internal medicine residency programmes in the United States. METHODS: A cross sectional survey of the programme directors and chief residents of each of the 407 accredited internal medicine programmes listed in the 1999-2000 Graduate Medical Education Directory. RESULTS: The questionnaire was returned by 231 of 404 (57%) programme directors and 233 of 404 (58%) chief residents. A chief and director of the same programme (paired responses) replied from 144 of 404 (36%) programmes surveyed. A formal sports medicine curriculum was reported by 22.1% of programme directors. Programmes with a formal curriculum were 2.9 times more likely to offer any of the sports medicine educational experiences (p<0.0001; Cochran-Mantel-Haenszel). Programmes with block rotations were more likely to include all of the educational experiences surveyed than those without (p<0.002 for each; chi(2) test). A total of 162 programmes included sports medicine as part of other rotations. Most programmes only included sports medicine as part of other rotations: 44.6% (103/231) of all programmes and 63.6% (103/162) of programmes with sports medicine as part of other rotations. Some 29.9% (69/231) of directors reported having an elective, and 3.9% (9/231) reported a required rotation. Almost a quarter (21.7%; 50/231) of directors reported that their residents received no clinical experience in sports medicine. CONCLUSIONS: Little attention is given to the subject of sports medicine when internal medicine residency curricula are developed in the United States. Thus only a small percentage of American internal medicine residency programmes provide significant training in sports medicine.

Clinical Competence↗