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Biomedical subjects

A Ray

Publications and source records attributed to A Ray.

At least 19 recordsLinked to original sources
PubMed2006

Vascular phenotype and subclinical inflammation in diabetic Asian Indians without overt cardiovascular disease.

Although Asian Indian (AI) patients with diabetes mellitus type 2 (DM2) are at high risk for cardiovascular disease (CVD), not all patients develop CVD. The vascular phenotype of AI-DM2 without CVD has not been elucidated and may point to protective features. Using baseline data from a clinical trial we provide an initial description of vascular parameters in AI-DM2 compared to Europid Caucasian controls (ECs) matched for age and gender. Endpoints of the study were endothelial function, low-grade systemic inflammation (CRP) and carotid intima-media thickness (cIMT). AIs had longer duration of diabetes, worse glycemic control and more microangiopathy. Both groups demonstrated marked endothelial dysfunction. CRP levels were similar: 1.7 (4.9) mg/L in AIs and 2.8 (3.6) mg/L in ECs. cIMT values were significantly lower in AI-DM2 than EC-DM2 (0.655mm (0.12) versus 0.711mm (0.15), p=0.03). Multiple regression analysis showed that variability in CRP was mainly determined by waist circumference, not by ethnicity. In contrast, ethnicity was a significantly explanatory variable for cIMT. Vascular phenotype of AI-DM2 without CVD was characterized by endothelial dysfunction and relatively low levels of CRP, comparable to EC-DM2 controls. In contrast, lower cIMT values were observed in AI-DM2 despite longer duration of diabetes and worse metabolic control. We propose that mechanisms slowing its progression may have atheroprotective potential in AI-DM2.

Adult↗
PubMed2006

AMN107 (nilotinib): a novel and selective inhibitor of BCR-ABL.

Chronic myelogenous leukaemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukaemia (ALL) are caused by the BCR-ABL oncogene. Imatinib inhibits the tyrosine kinase activity of the BCR-ABL protein and is an effective, frontline therapy for chronic-phase CML. However, accelerated or blast-crisis phase CML patients and Ph+ ALL patients often relapse due to drug resistance resulting from the emergence of imatinib-resistant point mutations within the BCR-ABL tyrosine kinase domain. This has stimulated the development of new kinase inhibitors that are able to over-ride resistance to imatinib. The novel, selective BCR-ABL inhibitor, AMN107, was designed to fit into the ATP-binding site of the BCR-ABL protein with higher affinity than imatinib. In addition to being more potent than imatinib (IC50< 30 nM) against wild-type BCR-ABL, AMN107 is also significantly active against 32/33 imatinib-resistant BCR-ABL mutants. In preclinical studies, AMN107 demonstrated activity in vitro and in vivo against wild-type and imatinib-resistant BCR-ABL-expressing cells. In phase I/II clinical trials, AMN107 has produced haematological and cytogenetic responses in CML patients, who either did not initially respond to imatinib or developed imatinib resistance. Dasatinib (BMS-354825), which inhibits Abl and Src family kinases, is another promising new clinical candidate for CML that has shown good efficacy in CML patients. In this review, the early characterisation and development of AMN107 is discussed, as is the current status of AMN107 in clinical trials for imatinib-resistant CML and Ph+ ALL. Future trends investigating prediction of mechanisms of resistance to AMN107, and how and where AMN107 is expected to fit into the overall picture for treatment of early-phase CML and imatinib-refractory and late-stage disease are discussed.

Animals↗
PubMed2006

RBx 7,796: A novel inhibitor of 5-lipoxygenase.

OBJECTIVE: To evaluate the pharmacological profile of RBx 7,796, a novel 5-lipoxygenase inhibitor. MATERIALS AND METHODS: RBx 7,796 was evaluated for 5- lipoxygenase inhibitory potential using human recombinant enzyme and profiled for selectivity against 12 and 15 lipoxygenase. RBx 7,796 was evaluated in cell based assay for inhibition of A23,187 induced LTB(4) release from isolated neutrophils. Ex vivo activity was evaluated for inhibition of A23,187 induced LTB(4) release in blood from treated rats. In vivo efficacy of RBx 7,796 was profiled in LPS induced neutrophilia model in rats and also in ovalbumin induced bronchoconstriction and airway inflammation models in guinea pigs. RESULTS: RBx 7,796, a novel chemotype, showed competitive inhibition of 5-lipoxygenase enzyme with an IC(50) of 3.5 +/- 1.1 microM. RBx 7,796 offered >100 fold selectivity against other related enzymes - 12 and 15 lipoxygenase. RBx 7,796 inhibited release of LTB(4) from human and rat neutrophils in vitro. Upon administration to rats, RBx 7,796 inhibited A23,187 induced LTB(4) release from rat neutrophils. Upon repeated administration, dosed once daily, RBx 7,796 inhibited LPS induced neutrophil influx in rat airway. RBx 7,796 also inhibited allergen induced bronchoconstriction and eosinophil influx in guinea pig airway in a dose dependent manner. CONCLUSION: The results suggest that RBx 7,796, a novel chemotype, is an orally efficacious inhibitor of 5-lipoxygenase enzyme that is effective against both neutrophilic and eosinophilic airway inflammation and shows potent inhibition with once daily administration.

Animals↗
PubMed2005

Subcutaneous depot medroxyprogesterone acetate versus leuprolide acetate in the treatment of endometriosis-associated pain.

BACKGROUND: A clinical study compared efficacy and safety of depot medroxyprogesterone acetate (DMPA) with leuprolide for endometriosis-associated pain. METHODS: This multicentre, 18 month, evaluator-blinded, comparator-controlled trial randomized 300 women with laparoscopically diagnosed endometriosis to 6 month treatment with subcutaneous injection of 104 mg/0.65 ml DMPA (DMPA-SC 104) every 3 months or leuprolide (3.75 mg monthly or 11.25 mg every 3 months), with 12 months post-treatment follow-up. Endpoints included patient response to treatment in five signs/symptoms (dysmenorrhoea, dyspareunia, pelvic pain, pelvic tenderness, induration) and changes in bone mineral density (BMD) and productivity at 6 and 18 months. RESULTS: DMPA-SC 104 and leuprolide produced equivalent (P < 0.02) reductions in at least four pain categories and significant (P < 0.001) improvements in composite score at months 6 and 18. At month 6, reductions in total hip and lumbar spine BMD were significantly less (P < 0.001) with DMPA-SC 104 versus leuprolide. BMD returned to pre-treatment levels 12 months post-treatment in the DMPA-SC 104 but not the leuprolide group. Total productivity also significantly (P < or = 0.05) improved in both groups at 6 and 18 months. CONCLUSIONS: DMPA-SC 104 reduces endometriosis-associated pain as effectively as leuprolide and improves productivity with significantly less BMD decline.

Administration, Cutaneous↗
PubMed2005

Detection of a radio counterpart to the 27 December 2004 giant flare from SGR 1806-20.

It was established over a decade ago that the remarkable high-energy transients known as soft gamma-ray repeaters (SGRs) are located in our Galaxy and originate from neutron stars with intense (< or = 10(15)G) magnetic fields-so-called 'magnetars'. On 27 December 2004, a giant flare with a fluence exceeding 0.3 erg cm(-2) was detected from SGR 1806-20. Here we report the detection of a fading radio counterpart to this event. We began a monitoring programme from 0.2 to 250 GHz and obtained a high-resolution 21-cm radio spectrum that traces the intervening interstellar neutral hydrogen clouds. Analysis of the spectrum yields the first direct distance measurement of SGR 1806-20: the source is located at a distance greater than 6.4 kpc and we argue that it is nearer than 9.8 kpc. If correct, our distance estimate lowers the total energy of the explosion and relaxes the demands on theoretical models. The energetics and the rapid decay of the radio source are not compatible with the afterglow model that is usually invoked for gamma-ray bursts. Instead, we suggest that the rapidly decaying radio emission arises from the debris ejected during the explosion.

Journal Article↗
PubMed2004

Venous angioma of the facial nerve: a case report.

BACKGROUND: Lower motor neurone type facial nerve palsy is a common condition that is very rarely caused by a neoplastic lesion. CASE DESCRIPTION: This case report describes a progressive facial palsy in a 62-year-old man because of a vascular tumor of the facial nerve. Histologic examination confirmed it to be a venous angioma. CONCLUSION: Meticulous imaging of the facial nerve is required to diagnose cases of progressive facial nerve palsy caused by a neoplastic lesion.

Facial Nerve↗
PubMed2004

Spinal subdural haematoma: how relevant is the INR?

STUDY DESIGN: Case report. OBJECTIVE: To report a rare cause of spinal cord compression. SETTING: University Hospital, Wales, UK. CASE REPORT: A 67-year-old gentleman on oral anticoagulation for atrial fibrillation presented with a 4-h history of progressive loss of sensation and weakness in both legs; there was no history of trauma. On examination, he had a flaccid paraplegia with altered sensation in the L1,2,3 dermatomes and complete anaesthesia in the L4,5 distribution. Knee and ankle jerk reflexes were absent, plantars were equivocal and anal sphincter tone was reduced. The patient's international normalized ratio (INR) was 4.1. An MR scan showed an extensive intradural haematoma compressing the cauda equina. The anticoagulation was reversed and an urgent T12-L2 laminectomy was performed; findings were a circumferential haematoma at L1 extending in the anterior canal between T10 and L3. The patient had an uneventful postoperative course generally, but at 1 week there was no neurological recovery. CONCLUSION: This case highlights that anticoagulation even when well controlled is not without risk. This is particularly of concern as the number of patients receiving long-term anticoagulation therapy has doubled between 1993 and 1998.

Aged↗
PubMed2004

Complications after trans-sphenoidal surgery: our experience and a review of the literature.

The incidence of surgical complications after trans-sphenoidal surgery for pituitary lesions is low. The influence of size of the lesion and its pathology on the incidence of different types of complications and the remission rate of functioning adenomas are addressed in this retrospective study. Between 1996 and 2001, 126 trans-sphenoidal operations were performed on 108 patients with pituitary pathologies. Diabetes insipidus (DI) was the commonest (23%) and the incidence was higher with microadenomas and in those with Cushing's disease (p < 0.05). Other important complications were: postoperative hypopituitarism 22%, CSF leak 13%, meningitis 5.5%, pneumocephalus 2.4%, visual deterioration 1.5%, haematoma 0.8% and 30-day mortality rate of 0.8%. Other complications encountered were subdural haematoma, epistaxis, SIADH, sphenoid abscess, deep vein thrombosis, thalamic infarct and hydrocephalus. No vascular injuries were encountered. The overall remission rate for acromegaly and Cushing's disease (22 patients each) was 77 and 81%, respectively. The remission rate was 100% for microadenomas, 89% for both acromegaly and Cushing's disease. More aggressiveness towards complete tumour removal increases the biochemical cure rate of functioning adenomas and on the other hand results in higher incidence of CSF leak and hypopituitarism.

Adenoma↗
PubMed2004

Advances in the treatment of pediatric brain tumors.

Brain tumors are a heterogeneous group of neoplasms with different origins, pathobiologies, treatments and prognoses. The collective contributions from the fields of neuro-oncology, neurosurgery, radiation oncology, neurology, neuropathology, neuroradiology and molecular biology have all led to significant advances in the treatment of certain brain tumors. Ideas from these fields, under the cooperative umbrella of clinical cancer trial consortia, have been tested in large-scale studies. As a result, patient survivals have increased markedly for these tumor types. Unfortunately, there are certain brain tumors in childhood, such as the diffuse intrinsic pontine glioma and atypical teratoid rhabdoid tumor, for which survival advantages have not been found. This review will discuss the current and possible future therapies of the most common pediatric brain tumors and highlight some of the novel imaging modalities that are used pre- and intraoperatively.

Astrocytoma↗
PubMed2004

Facial characterization of infants with cleft lip and palate using a three-dimensional capture technique.

OBJECTIVE: To characterize the soft tissue features of infants with unilateral cleft lip (UCL) and unilateral complete cleft lip and palate (UCLP) prior to primary surgery and compare with noncleft controls. DESIGN: Prospective controlled capture of the facial morphology of infants using a noninvasive three-dimensional stereophotogrammetry method. PARTICIPANTS: 23 children with presurgical cleft: 11 UCL (M = 6, F = 5); 12 UCLP (M = 9, F = 3), and 21 noncleft controls (M = 7, F = 14) were imaged at approximately 3 months of age (range 10 to 16 weeks). MAIN OUTCOME MEASURE: Accurate, repeatable quantification of facial soft tissues in infants with clefts prior to surgery. RESULTS: Significant differences (p <.05) were found between the UCLP group and UCL and control groups in anatomical and soft nose width, cleft-side alar wing length, and nasal tip horizontal displacement. Both cleft groups were significantly different from controls and from each other in cleft-side nostril dimensions, alar wing angulation, columella angle, and alar base to corner of mouth dimension; alar base width; and soft tissue defect in nose and the lip and philtrum length bordering the cleft. Significant differences between clefts and controls were identified in the nostril and philtrum on the noncleft side. CONCLUSIONS: The use of children with UCL as controls for UCLP studies is inappropriate. This technique overcame the limitations of direct measurement of infant faces to aid the surgeon in the planning and subsequent re-evaluation of surgical rationale.

Analysis of Variance↗
PubMed2004

Acceptability of traditional healers as directly observed treatment providers in tuberculosis control in a tribal area of Andhra Pradesh, India.

SETTING: Vizianagaram district of Andhra Pradesh, India, where 9% of the population is tribal. OBJECTIVE: To 1) examine traditional healers' (THs) diagnostic and treatment practices for tuberculosis (TB); 2) understand health-seeking behaviour for TB amongst tribal groups; 3) evaluate the acceptability of THs to public health workers; and 4) assess how THs can collaborate with the TB Programme. METHODS: In-depth interviews with 120 THs, 37 exit interviews and four focus group discussions with TB patients; interviews with eight non-governmental organisations (NGOs) and 38 public health staff. RESULTS: There were 18 THs per 1000 population. Of the 120 THs interviewed, 15 (13%) claimed to be TB specialists. Of the 72 healers aware of TB, 65 (90%) considered prolonged cough an important symptom and 53 (74%) believed that TB could be cured with allopathic drugs. THs felt collaboration was possible by directly observed treatment (DOT) providers (49, 68%), referring symptomatic individuals (54, 75%) and offering treatment for side effects (18, 25%). CONCLUSION: Involvement of THs in the TB Control Programme may improve services as they are a major health service provider in tribal areas and are acceptable as DOT providers to patients, public health providers and NGO workers.

Attitude of Health Personnel↗
PubMed2004

Effect of body temperature on mortality of acute stroke.

OBJECTIVES: The exact relation between body temperature and mortality of acute stroke victims is poorly understood. However, body temperature can affect the outcome of stroke cases in relation to mortality. In the initial (4-12 hrs) hours of stroke, the temperature rise is often neurogenic in origin and mortality is also higher with raised body temperature. Though the anatomical lesion or nature of lesion along with other established risk factors influence the mortality of stroke cases, change in temperature does affect the outcome of stroke cases. We sought to find out the significance of stroke victim's body temperature (within 4-12 hrs) with respect to short-term mortality rate in our study. METHODS: We selected 100 ischemic and 100 hemorrhagic stroke patients proved by CT scan of brain and 2-hrly oral temperature was strictly recorded for the initial 4-12 hrs of admission. RESULTS: It was evident from the study that hyperthermia (>37.5 degrees C) was associated with highest mortality rate in both hemorrhagic (51.78%) and ischemic (56.66%) cases. In normothermic group, mortality was 13.5% and 8.8% in hemorrhagic and ischemic group respectively, whereas hypothermia (<36.5 degrees C) was associated with 0 % mortality. CONCLUSION: Hyperthermia in acute stroke victim carries a bad prognostic parameter in short term basis.

Acute Disease↗
PubMed2003

Validation of a vision-based, three-dimensional facial imaging system.

OBJECTIVE: The aim of this study was to assess the accuracy of a newly developed three-dimensional (3D) imaging system in recording facial morphology. METHODS: Twenty-one infants with cleft lip each had a full-face alginate impression taken at the time of primary lip repair, and a stone cast was constructed from each impression. Five anthropometric points were marked on each cast. Each cast was digitized, and the 3D co-ordinates of the five points were obtained using a co-ordinate measuring machine (CMM, Ferranti) of documented accuracy (9.53 microm). Each cast was scanned in four positions using a computerized stereophotogrammetry (C3D) system. The five points were located on the 3D images, and their 3D co-ordinates were extracted by three operators. The co-ordinate systems produced by C3D were aligned, via translation and rotation, to match the CMM co-ordinate system using partial ordinary procrustes analysis. The displacements of the adjusted C3D co-ordinates from the reference co-ordinates were then measured. Three different types of errors were identified: operator, system, and registration errors. RESULTS: Operator error was within 0.2 mm of the true co-ordinates of the landmarks. C3D was accurate within 0.4 mm. The average displacement of points over the 21 casts at four positions for the three operators was 0.79 mm (median 0.68). CONCLUSIONS: The presented 3D imaging system is reliable in recording facial deformity and could be utilized in recording cleft deformities and measuring the changes following surgery

Cephalometry↗
PubMed2003

An appraisal of three methods of rating facial deformity in patients with repaired complete unilateral cleft lip and palate.

OBJECTIVES: To evaluate the reliability of clinical assessment, two-dimensional color transparencies and three-dimensional imaging for evaluating the residual facial deformity in patients with repaired complete unilateral cleft lip and palate (UCLP) and compare the ratings of facial deformity made by health care professionals with those made by lay assessors. PATIENTS AND PARTICIPANTS Thirty-one randomly selected subjects aged 10 to 30 years with repaired complete UCLP. Five professionals and five laypersons evaluated each subject's residual cleft-related facial deformity using clinical assessment, two-dimensional color transparencies, and three-dimensional images. MAIN OUTCOME MEASURES: The facial deformity of the full face, lip, nose, and midface were scored using a 5-point ordinal scale on two occasions with a 1-month interval. Intra- and interexaminer agreements were calculated from weighted kappa statistics. Bootstrap permutation tests were used to detect any differences in agreement. RESULTS: Assessment of facial deformity showed good reproducibility across the three assessment media (kappa = 0.42 to 0.83, SE 0.08). Clinical assessment among lay assessors, however, was poor to moderate (kappa = 0.16 to 0.58, SE 0.07). For all assessors, there was no difference in the two nonclinical media relative to the standard clinical assessment for assessments of the full face (p =.377). For assessments of the lip or nose, transparency scores were in greater agreement with the clinical scores than were the three-dimensional assessment scores (p =.017 and.011, respectively). For rating the midface, the three-dimensional scores were in greater agreement with the clinical scores than were the color transparencies scores (p =.047). CONCLUSIONS: In comparison with lay assessors, clinical assessment among professionals was more reproducible. This was not so for nonclinical media. The equivalence of using the color transparencies and three-dimensional media relative to the clinical assessment depends on the region of the face being considered.

Adolescent↗