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Biomedical subjects

V Patel

Publications and source records attributed to V Patel.

At least 19 recordsLinked to original sources
PubMed2001

Spectrum of myelopathies in HIV seropositive South African patients.

The authors determined the cause of myelopathies in 33 HIV seropositive individuals in KwaZulu/Natal, South Africa. The main associations were with human T-cell lymphotrophic virus-I, tuberculosis, herpes zoster, and syphilis. A novel association with probable bilharziasis was noted. Only one case of vacuolar myelopathy was identified. Opportunistic infections will probably persist until routine antiretroviral therapy becomes widely available in South Africa.

Adult↗
PubMed2001

Crystal structure of rabbit phosphoglucose isomerase complexed with its substrate D-fructose 6-phosphate.

Phosphoglucose isomerase (PGI, EC 5.3.1.9) catalyzes the interconversion of D-glucose 6-phosphate (G6P) and D-fructose 6-phosphate (F6P) and plays important roles in glycolysis and gluconeogenesis. Biochemical characterization of the enzyme has led to a proposed multistep catalytic mechanism. First, the enzyme catalyzes ring opening to yield the open chain form of the substrate. Then isomerization proceeds via proton transfer between C2 and C1 of a cis-enediol(ate) intermediate to yield the open chain form of the product. Catalysis proceeds in both the G6P to F6P and F6P to G6P directions, so both G6P and F6P are substrates. X-ray crystal structure analysis of rabbit and bacterial PGI has previously identified the location of the enzyme active site, and a recent crystal structure of rabbit PGI identified Glu357 as a candidate functional group for transferring the proton. However, it was not clear which active site amino acid residues catalyze the ring opening step. In this paper, we report the X-ray crystal structure of rabbit PGI complexed with the cyclic form of its substrate, D-fructose 6-phosphate, at 2.1 A resolution. The location of the substrate relative to the side chains of His388 suggest that His388 promotes ring opening by protonating the ring oxygen. Glu216 helps to position His388, and a water molecule that is held in position by Lys518 and Thr214 accepts a proton from the hydroxyl group at C2. Comparison to a structure of rabbit PGI with 5PAA bound indicates that ring opening is followed by loss of the protonated water molecule and conformational changes in the substrate and the protein so that a helix containing amino acids 513-520 moves in toward the substrate to form additional hydrogen bonds with the substrate.

Amino Acids↗
PubMed2001

Transradial renal angioplasty: initial experience.

We report our early experience of a new technique of renal angioplasty utilizing the radial approach. Certain anatomic considerations continue to make access from above via the arm the preferable approach in selected patients in renal artery stenosis. We have utilized the transradial technique for renal artery angioplasty and stenting successfully in four patients. The development of coronary guidewire (0.014")-based peripheral balloons and stent delivery systems has miniaturized equipment sufficiently to make the transradial approach attractive. Present equipment allows for stenting of renal arteries of up to 7 mm with the use of 6 Fr guiding catheters. Present equipment length remains a limitation in taller patients. The transradial approach should be considered in those patients with renal artery or aortoiliac anatomy favoring an approach from the arm.

Aged↗
PubMed2001

Acute doxorubicin (adriamycin) dosage does not reduce cardiac protein synthesis in vivo, but decreases diaminopeptidase I and proline endopeptidase activities.

Anthracycline antibiotics are effective anticancer agents but their use is limited due to unwanted adverse side effects. The toxic effects of doxorubicin (adriamycin) include the development of defined cardiac lesions leading to cardiomyopathy in some patients. This has been reported to be due to reductions in cardiac protein synthesis. However, virtually all of these previous studies have failed to consider the specific radioactivity of the precursor pool in their measurements or have carried out their studies in vitro. To further resolve the above we measured fractional rates of cardiac protein synthesis using the "flooding dose" method in rats treated with adriamycin (5 mg/kg body wt). Controls were identically treated and injected with saline. At 2.5 or 24 h after adriamycin injection, rates of protein synthesis were measured with a flooding dose of l-[4-(3)H]phenylalanine. Measurements included free (S(i)) and protein-bound (S(b)) phenylalanine-specific radioactivities, the protein synthetic capacity (RNA/protein ratio; C(s)), the fractional rates of protein synthesis calculated from the ratio S(b)/S(i), and the protein synthetic efficiency calculated from the ratio k(s)/C(s). Complementary analyses included assays of lysosomal (cathepsins B, D, H, and L and diaminopeptidases I and II) and cytoplasmic proteases (alanyl aminopeptidase, arginyl aminopeptidase, leucyl aminopeptidase, diaminopeptidase IV, tripeptidyl aminopeptidase, and proline endopeptidase). These enzymes constitute the most active proteases in this tissue and represent an index of protein degradation capacity in cardiac muscle. The results showed that in 2.5-h dosed rats, adriamycin had no effect on S(i), S(b), C(s), k(s), or k(RNA) (P > 0.05, not significant (NS) in all instances). In 2.5-h dosed rats, levels of diaminopeptidase I activity were reduced (P < 0.05), whereas the activities of other proteases were not significantly altered (NS in all instances). In 24-h dosed rats, adriamycin reduced cardiac S(b) (P < 0.001), which would normally be interpreted as a reduction in protein synthesis. However, S(i) was also decreased in 24-h adriamycin-injected rats (P < 0.025%). C(s) was not changed (NS). Consequently, the calculated k(s) and k(RNA) values were not significantly affected in 24-h adriamycin-dosed rats (NS). There were also significant reductions in proline endopeptidase activities in rats exposed for 24 h to adriamycin. The activities of other proteases were not significantly affected at this time point (NS in all instances). In conclusion, adriamycin reduces amino acid labeling of cardiac proteins, an effect that is a consequence of altered free phenylalanine-specific radioactivities. There was some evidence of limited altered intracellular proteolysis.

Animals↗
PubMed2001

Ageing and mental health in a developing country: who cares? Qualitative studies from Goa, India.

BACKGROUND: While there is a growing body of epidemiological evidence on the prevalence of mental illnesses in late-life in developing countries, there is limited data on cultural perceptions of mental illnesses and care arrangement for older people. METHOD: This qualitative study used focus group discussions with older people and key informants to investigate the status of older people and concepts of late-life mental health conditions, particularly dementia and depression, in Goa, India. RESULTS: Vignettes of depression and dementia were widely recognized. However, neither condition was thought to constitute a health condition. Dementia was construed as a normal part of ageing and was not perceived as requiring medical care. Thus, primary health physicians rarely saw this condition in their clinical work, but community health workers frequently recognized individuals with dementia. Depression was a common presentation in primary care, but infrequently diagnosed. Both late-life mental disorders were attributed to abuse, neglect, or lack of love on the part of children towards a parent. There was evidence that the system of family care and support for older persons was less reliable than has been claimed. Care was often conditional upon the child's expectation of inheriting the parent's property. Care for those with dependency needs was almost entirely family-based with little or no formal services. Unsurprisingly, fear for the future, and in particular 'dependency anxiety' was commonplace among older Goans. CONCLUSIONS: There is a need to raise awareness about mental disorders in late-life in the community and among health professionals, and to improve access to appropriate health care for the elderly with mental illness. The study suggests directions for the future development of locally appropriate support services, such as involving the comprehensive network of community health workers.

Aged↗
PubMed2001

Prospective analysis of relationships of outcome measures for ulnar neuropathy at the elbow.

BACKGROUND: We undertook a prospective study to investigate relationships between outcome measures of ulnar neuropathy at the elbow. METHODS: Thirty-one patients (mean age 52.6, range 20-80), with clinically and electrically verified ulnar neuropathy at the elbow, were seen independently by a neurosurgeon and a physiotherapist. All tests were administered to all patients on each visit. Data collected included measures of sensory (monofilament, two-point discrimination, vibration) and motor function (grip, key-pinch, muscle atrophy), pain (visual analogue scale (VAS)) and impact on lifestyle (Levine's questionnaires (function status score--FSS, symptom severity score--SSS)), disability of the arm, shoulder and hand module (DASH) and patient-specific measures (PSM). Parametric and non-parametric correlation and factor analysis were done. RESULTS: Outcome analysis was available for 63 patient visits, with follow-up obtained for 20 patients (mean 8.5 months). Lifestyle and pain instruments (FSS, SSS, DASH, PSM and VAS) all correlated well with each other (r > 0.6, p < .01). DASH was moderately to highly correlated to nine of the 11 measures. Some tests correlated poorly, for example, Semmes-Weinstein monofilament with other sensory measures and muscle atrophy with almost all measures. Factor analysis revealed that there are two principal factors, accounting for 77% of the variance. Factor 1 relates to impact on lifestyle and pain while Factor 2 relates to strength and function. DISCUSSION/CONCLUSIONS: Intraclass measures, particularly ones assessing lifestyle and pain instruments are strongly correlated. Factor analysis revealed two principal factors that account for the majority of the variance; future studies with a larger sample size are needed to validate this analysis.

Adult↗
PubMed2001

Unipolar defibrillator?

An unusual case of "unipolar" pacing and myopotential over-sensing leading to an inappropriate ICD shock in a patient with an implanted defibrillator is reported. The reasons for unipolar behavior in a system using a committed bipolar device are discussed.

Algorithms↗
PubMed2001

Fatal emphysematous pyelonephritis with gas in the spinal extradural space in a patient with diabetes.

BACKGROUND: Emphysematous pyelonephritis (EP) is a rare but life-threatening condition of the upper urinary tract, characterized by the presence of gas in the renal parenchyma and perirenal space. The vast majority of patients with EP (90%) are known to have diabetes, with Escherichia coli being the most common causative pathogen. CASE REPORT: We present a case of fatal bilateral EP in a patient with diabetes, with an unusual radiological finding of gas around the spinal cord and in the psoas muscle, with renal parenchymal sparing. Our case serves as an important reminder of this life threatening entity in diabetic patients, which is not well recognized by clinicians because of its rarity.

Diabetes Mellitus, Type 2↗
PubMed2001

Clinical outcome of a cohort of patients eligible for therapeutic angiogenesis or transmyocardial revascularization.

BACKGROUND: Newer methods of coronary revascularization are being investigated in patients who are not candidates for coronary artery bypass grafting or percutaneous intervention. Our objective was to determine the proportion of patients eligible for newer methods of revascularization and determine their 1-year clinical outcome. METHODS: Five hundred consecutive charts and angiograms from patients undergoing diagnostic angiography for coronary artery disease from January to May of 1998 were reviewed to assess the suitability for revascularization. Patients ineligible for conventional revascularization were followed up for 1 year. RESULTS: Fifty-nine patients of the 500 studied were identified who had refractory ischemia but were not candidates for traditional revascularization. The 59 patients ineligible for traditional methods of revascularization had a rehospitalization rate of 128% (76 total hospitalizations), a 25.5% rate of myocardial infarction (15 of 59), and a mortality rate of 16.9% (10 of 59). CONCLUSIONS: The prognosis of many patients eligible for newer methods of revascularization on maximal medical therapy is poor.

Aged↗
PubMed2001

Cultural factors and international epidemiology.

The debate on the role of culture on psychiatric epidemiology has evolved considerably in the past two decades. There is now a general consensus that the integration of the universalist and culturally relativist approaches, and their methodologies, is required to generate a truly international psychiatric epidemiology. The large body of research investigating the influence of culture on the epidemiology of depression has produced a number of key findings: the clinical presentation of depression in all cultures is associated with multiple somatic symptoms of chronic duration; psychological symptoms, however, are important for diagnosis and can be easily elicited. The diagnostic differentiation between depression and anxiety in general health care settings is not clinically valid. Culturally appropriate terminology for depression can be identified and their use may improve levels of recognition and treatment compliance. It is also evident that culture is only one factor in the difference between, and within, human societies which has a bearing on the epidemiology of depression. Other factors, which may interact with culture, such as gender and income inequality, are major risk factors for depression. Future international research must focus on two themes: (i) intervention studies including cost-effectiveness outcomes; and (ii) research aiming to bridge the gap between regional public health priorities and the concern that psychiatrists have about depression.

Community Mental Health Services↗
PubMed2001

Stability after medial collateral ligament release in total knee arthroplasty.

Six knees from cadavers were tested for change in stability after release of the medial collateral ligament with posterior cruciate-retaining and substituting total knee replacements. Load deformation curves of the joint were recorded in full extension and 30 degrees, 60 degrees, and 90 degrees flexion under a 10 N-m varus and valgus torque, 1.5 N-m internal and external rotational torque, and a 35 N anterior and posterior force to test stability in each knee. The intact specimen and posterior cruciate ligament-retaining total joint replacement were tested for baseline comparisons. The superficial medial collateral ligament was released, followed by release of the posterior cruciate ligament. The knee then was converted to a posterior-stabilized implant. After medial collateral ligament release, valgus laxity was statistically significantly greater at 30 degrees, 60 degrees, and 90 degrees flexion after posterior cruciate ligament sacrifice than it was when the posterior cruciate ligament was retained. The posterior-stabilizing post added little to varus and valgus stability. Small, but significant, differences were seen in internal and external rotation before and after posterior cruciate ligament sacrifice. The posterior-stabilized total knee arthroplasty was even more rotationally constrained in full extension than the knee with intact medial collateral ligament and posterior cruciate ligament.

Arthroplasty, Replacement, Knee↗
PubMed2001

The structure of apo protein-tyrosine phosphatase 1B C215S mutant: more than just an S --> O change.

Protein-tyrosine phosphatases catalyze the hydrolysis of phosphate monoesters via a two-step mechanism involving a covalent phospho-enzyme intermediate. Biochemical and site-directed mutagenesis experiments show that the invariant Cys residue present in the PTPase signature motif (H/V)CX(5)R(S/T) (i.e., C215 in PTP1B) is absolutely required for activity. Mutation of the invariant Cys to Ser results in a catalytically inactive enzyme, which still is capable of binding substrates and inhibitors. Although it often is assumed that substrate-trapping mutants such as the C215S retain, in solution, the structural and binding properties of wild-type PTPases, significant differences have been found in the few studies that have addressed this issue, suggesting that the mutation may lead to structural/conformational alterations in or near the PTP1B binding site. Several crystal structures of apo-WT PTP1B, and of WT- and C215S-mutant PTP1B in complex with different ligands are available, but no structure of the apo-PTP1B C215S has ever been reported. In all previously reported structures, residues of the PTPase signature motif have an identical conformation, while residues of the WPD loop (a surface loop which includes the catalytic Asp) assume a different conformation in the presence or absence of ligand. These observations led to the hypothesis that the different spectroscopic and thermodynamic properties of the mutant protein may be the result of a different conformation for the WPD loop. We report here the structure of the apo-PTP1B C215S mutant, which reveals that, while the WPD loop is in the open conformation observed in the apo WT enzyme crystal structure, the residues of the PTPases signature motif are in a dramatically different conformation. These results provide a structural basis for the differences in spectroscopic properties and thermodynamic parameters in inhibitor binding observed for the wild-type and mutant enzymes.

Amino Acid Sequence↗
PubMed2001

New approaches to the understanding of the molecular basis of oral cancer.

Cancers of the oral cavity, salivary glands, larynx, and pharynx, collectively referred to as squamous cell carcinomas of the head and neck (HNSCC), are the sixth most common cancer among men in the developed world. The prognosis of HNSCC patients is still poor, which reflects the fact that although the risk factors for HNSCC are well-recognized, very little is known about the molecular mechanisms responsible for this malignancy. This review describes some of the current efforts and technological advances that have focused on the creation of a complete information infrastructure for genes expressed during squamous cell carcinogenesis. These include: the recently described HNSCC-specific chromosomal alterations (cCAP); the Head and Neck Cancer Genome Anatomy Project (HN-CGAP), whose goal is the systematic identification and cataloguing of known and novel genes expressed during tumor development; and the use of laser-capture microdissection (LCM), which is pivotal for the comprehensive molecular characterization of normal, pre-cancerous, and malignant cells by means of DNA-array technology. The latter provides the means for the analysis of expression patterns of thousands of genes simultaneously. The use of LCM for proteomics and DNA analysis is also included in this review. These revolutionary approaches are likely to have an unprecedented impact on cancer biology, and provide exciting opportunities to unravel the still-unknown mechanisms involved in squamous cell carcinogenesis. They are also expected to provide a molecular blueprint for HNSCC, thus helping to identify suitable markers for the early detection of preneoplastic lesions, as well as novel targets for pharmacological intervention in this disease.

Carcinoma, Squamous Cell↗
PubMed2001

International representation in psychiatric literature: survey of six leading journals.

BACKGROUND: Despite the growing recognition of the global burden of psychiatric disease, there are questions about the strength of the evidence base from non-Western societies. AIMS: To compare the contribution of Euro-American countries and the rest of the world (RoW) to psychiatric literature. METHOD: Survey of the country of origin of papers submitted to and published in six leading psychiatric journals over a 3-year period (1996-1998). RESULTS: Only 6% of the literature is published from regions of the world that account for over 90% of global population. The three journals published in Europe had a significantly higher proportion of international articles when compared to the three American journals. Less than 1% of all published articles described mental health interventions in the ROW: Acceptance rates were significantly lower for papers submitted from the ROW: CONCLUSIONS: There is a gross under-representation of research from the ROW: This has implications for the development of a truly international psychiatry.

Bibliometrics↗
PubMed2001

Ethnic classification in primary dental care and dental health services research: time to pause for thought.

'Ethnicity' is an important concept in dental health services research and in enabling general dental practitioners to gain insight into their patients values and expectations. Since more health services research is being undertaken in primary dental care settings it is becoming an important issue for dental professionals and researchers in primary care to be aware of. Ethnicity is thought to be related to dental health inequalities and access and is often used as a stratifying variable in many dental studies. The meaning and use of the term however differs among researchers and among the public. It is clear that researchers and professionals need to pause for thought when considering what this often bandied about term actually means and the impact of different definitions. This is illustrated using examples from the authors' own research and published papers in the medical and dental literature. There is also much debate about whether ethnicity--however defined--is an important predictor of differences in dental health in itself or is merely a marker for other factors such as social deprivation or the impact of 'place' on dental health. While the jury on this debate is out we suggest guidelines on the reporting of ethnicity should be outlined in the dental literature--perhaps updating those published in 1996 in the British Medical Journal.

Cultural Characteristics↗
PubMed2001

Euglycemic clamp study in clozapine-induced diabetic ketoacidosis.

OBJECTIVE: To describe the fifth case of clozapine-induced diabetic ketoacidosis (DKA) with complete resolution of abnormal glucose metabolism after discontinuation of clozapine as assessed by oral glucose tolerance testing (OGTT) and the first to be serially studied with markers of pancreatic autoimmunity; to demonstrate insulin resistance using the euglycemic clamp study and reduced pancreatic insulin reserve using intravenous glucose tolerance testing (IVGTT) in clozapine-induced diabetes mellitus and DKA, when the OGTT was normal; and to systematically review the previously described cases of clozapine-induced diabetes mellitus and DKA. CASE SUMMARY: A 33-year-old white man without past or family history of diabetes mellitus presented with DKA after eight months of clozapine therapy (50 mg twice daily). After treatment of DKA and discontinuation of clozapine, glucose tolerance and concurrent serum insulin concentrations reverted to normal as measured by two OGTT performed 60 and 320 days after resolution of DKA. DISCUSSION: Antiislet-cell antibodies, antiglutamic acid decarboxylase antibodies, and human insulin antibody were negative on two separate occasions. Euglycemic clamp study demonstrated insulin resistance manifested by a glucose disposal rate of approximately 55% of mean normal values. IVGTT demonstrated a low rate of glucose disappearance (KG = 0.95) and diminished first-phase insulin response when OGTT was normal, indicating impairment in insulin sensitivity and reduction in beta cell function 323 days after discontinuance of clozapine. This adverse reaction is considered probable according to the Naranjo probability scale. CONCLUSIONS: The occurrence of cases of DKA and new or worsening diabetes mellitus in patients using clozapine suggests a causal relationship. We hypothesize that the mechanism by which clozapine may produce glucose intolerance may require a preexisting latent defect in insulin secretion and insulin action. With the administration of clozapine, some of these patients may develop worsening insulin resistance and may fail to mount an appropriate compensatory beta cell insulin secretion for the degree of insulin resistance. As a consequence, hyperglycemia develops and its persistence results in glucose toxicity, further suppressing beta cell insulin secretion. Such combined defects in insulin secretion and sensitivity are known to be synergistic, leading to the development of abnormal glucose tolerance, which can be clinically manifested as a spectrum ranging from impaired glucose tolerance through severe hyperglycemia to DKA. Patients being started on clozapine should be carefully followed for the development or worsening of diabetes mellitus, regardless of the dose of the drug.

Adult↗