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Biomedical subjects

M Patel

Publications and source records attributed to M Patel.

At least 19 recordsLinked to original sources
PubMed2006

Blockade of mGluR1 receptor results in analgesia and disruption of motor and cognitive performances: effects of A-841720, a novel non-competitive mGluR1 receptor antagonist.

BACKGROUND AND PURPOSE: To further assess the clinical potential of the blockade of metabotropic glutamate receptors (mGluR1) for the treatment of pain. EXPERIMENTAL APPROACH: We characterized the effects of A-841720, a novel, potent and non-competitive mGluR1 antagonist in models of pain and of motor and cognitive function. KEY RESULTS: At recombinant human and native rat mGluR1 receptors, A-841720 inhibited agonist-induced calcium mobilization, with IC50 values of 10.7+/-3.9 and 1.0 +/- 0.2 nM, respectively, while showing selectivity over other mGluR receptors, in addition to other neurotransmitter receptors, ion channels, and transporters. Intraperitoneal injection of A-841720 potently reduced complete Freund's adjuvant-induced inflammatory pain (ED50 = 23 micromol kg(-1)) and monoiodoacetate-induced joint pain (ED50 = 43 micromol kg(-1)). A-841720 also decreased mechanical allodynia observed in both the sciatic nerve chronic constriction injury and L5-L6 spinal nerve ligation (SNL) models of neuropathic pain (ED50 = 28 and 27 micromol kg(-1), respectively). Electrophysiological studies demonstrated that systemic administration of A-841720 in SNL animals significantly reduced evoked firing in spinal wide dynamic range neurons. Significant motor side effects were observed at analgesic doses and A-841720 also impaired cognitive function in the Y-maze and the Water Maze tests. CONCLUSIONS AND IMPLICATIONS: The analgesic effects of a selective mGluR1 receptor antagonist are associated with motor and cognitive side effects. The lack of separation between efficacy and side effects in pre-clinical models indicates that mGluR1 antagonism may not provide an adequate therapeutic window for the development of such antagonists as novel analgesic agents in humans.

Analgesia↗
PubMed2006

Antibodies against six human herpesviruses in relation to seven cancers in black South Africans: a case control study.

BACKGROUND: Infections with certain human herpesviruses have been established as risk factors for some cancer types. For example, Epstein-Barr Virus is considered a cause of Burkitt's lymphoma and other immunosuppression related lymphomas, Hodgkin lymphoma, and nasopharyngeal cancer. Several other human herpesviruses have been linked to cancers but the totality of evidence is inconclusive. METHODS: We conducted a systematic sub-study from within an ongoing case control study of adult black South Africans to investigate the relationship between antibodies to six human herpesviruses and seven cancer groups that may be caused by infectious agents. Subjects had incident cancers of the oral cavity (n = 88), the cervix (n = 53), the prostate (n = 66), Hodgkin lymphoma (n = 83), non-Hodgkin lymphoma (n = 80), multiple myeloma (n = 94) or leukaemia (n = 203). For comparison, patients with other cancers (n = 95) or cardiovascular disease (n = 101) were randomly selected from within the study. Patients were interviewed and their blood was tested for IgG antibodies against HSV-1, HSV-2, VZV, EBV-EBNA, CMV and HHV-6 using enzyme linked immunosorbent assays. Because these viruses are highly prevalent in this population, optical density results from the assays were used as an indirect, quantitative measure of antibody level. RESULTS: There was significant variation in the mean log antibody measures for HSV-2, VZV, CMV and HHV-6 between the disease groups. However, none of the specific cancer groups had significantly higher mean log antibody measures for any of the viruses compared to either control group. In a more detailed examination of seven associations between cancers and herpesviruses for which there had been prior reports, two statistically significant associations were found: a decreasing risk of myeloid leukaemia and an increasing risk of oral cancer with increasing tertiles of antibodies against HHV-6 compared to all other patients (p-trend = 0.03 and 0.02, respectively). Odds ratios for the top tertile compared to the bottom tertile were 0.58 (95%CI 0.3-1.0) for myeloid leukaemia and 2.21 (95% CI 1.1-4.3) for oral cancer. CONCLUSION: In this population, using these tests for IgG, neither mean antibody measure nor high antibody measure against human herpesviruses 1-6 was strongly associated with any of the seven cancer groups. However, we may not have had sufficient power to detect weak associations or associations with a sub-type of cancer if they were present.

Journal Article↗
PubMed2006

Access to bone mineral density testing in patients at risk for osteoporosis.

INTRODUCTION: Prior studies have documented suboptimal diagnosis and treatment for osteoporosis in many settings. Consistent predictors of suboptimal management include patient age, physician training, and physician gender. We assessed whether access to bone mineral density (BMD) testing was a predictor of osteoporosis management in an at-risk population of patients from New Jersey. METHODS: Based on health care claims data, we identified three groups of at-risk beneficiaries, including women >or=65 (n=8,283), men and women >or=45 with a fracture (n=740), and men and women >or=45 taking chronic oral glucocorticoids (n=616). As the outcome of interest, we determined whether beneficiaries had undergone a BMD test and/or filled a prescription for a medicine used for osteoporosis (alendronate, calcitonin, hormone therapy, etidronate, risedronate, raloxifene, teriparatide) during the period 1 September 2002-31 August 2004. We assessed the relationship between this outcome and access to BMD testing. Access was characterized using two different measures: (1) the estimated driving time between each beneficiary's residence and the nearest BMD testing center ("driving time") and (2) the number of persons >or=65 years of age per BMD testing machine ("BMD scanner ratio") for each of the 21 counties in New Jersey. RESULTS: Of the 9,640 beneficiaries, we found that 3,104 (32%) had undergone a BMD test, 2,893 (30%) had filled a prescription for an osteoporosis medication, and 4,364 (45%) had one or both. Across the 21 counties of New Jersey, the percentage of at-risk patients who had a BMD test and/or medication for osteoporosis ranged from 38 to 52%. In models adjusted for patient factors and the clustering of patients in counties, driving time was not associated with patients being screened or treated for osteoporosis. The BMD scanner ratio was a weak predictor of osteoporosis management. CONCLUSION: Among beneficiaries of one large health insurer in New Jersey, two different measures of access to BMD testing were not important predictors of receiving testing and/or medications for osteoporosis.

Age Distribution↗
PubMed2006

(B2) Periodontal diseases and other bacterial infections.

The workshop addressed the following questions with respect to periodontal diseases and bacterial infections seen in HIV infection: (1) What is linear gingival erythema? Is it prevalent only in HIV disease? A crude Delphi technique was used to ascertain whether LGE existed, but a consensus could not be reached. It was agreed that a diagnosis of LGE should be considered only if the lesion persists after removal of plaque in the initial visit. (2) Do periodontal pockets contribute to viremia in HIV infection? At present, the data are not available to answer this question. (3) Do anti-viral drugs reach the sulcular fluid in significant concentrations? No one at the workshop was aware of data that could answer this question. (4) Does concurrent tuberculosis infection modify the oral manifestations of HIV infection? Though analysis of data from the developing countries does suggest an association between tuberculosis and oral candidiasis, more data and multivariate analysis considering immunosuppression as a confounding factor are necessary, for any conclusions to be derived. (5) What pathogens are involved in periodontal diseases in HIV infection? Periodontal disease may be initiated by conventional periodontal pathogens. But the progression and tissue destruction depend upon the presence of typical and atypical micro-organisms, including viruses, their by-products, increased secretion of potentially destructive inflammatory mediators, and overwhelming host response. (6) How can we diagnose the diseases seen in HIV infection? The answer can be obtained only with data from controlled and blinded studies. It is necessary to design collaborative multi-center longitudinal studies. The results obtained from such large sample sizes can contribute eventually to interpretation of the outcome.

AIDS-Related Opportunistic Infections↗
PubMed2006

Influenza M2 envelope protein augments avian influenza hemagglutinin pseudotyping of lentiviral vectors.

Lentivirus-based gene transfer has the potential to efficiently deliver DNA-based therapies into non-dividing epithelial cells of the airway for the treatment of lung diseases such as cystic fibrosis. However, significant barriers both to lung-specific gene transfer and to production of lentivirus vectors must be overcome before these vectors can be routinely used for applications to the lung. In this study, we investigated whether the ability to produce lentiviral vectors pseudotyped with fowl plague virus hemagglutinin (HA) could be improved by co-expression of influenza virus M2 in vector-producing cells. We found that M2 expression led to a 10-30-fold increase in production of HA-pseudotyped lentivirus vectors based upon equine infectious anemia virus (EIAV) or human immunodeficiency virus type 1 (HIV-1). Experiments using the M2 inhibitor amantadine and a drug-resistant mutant of M2 established that the ion channel activity of M2 was important for M2-dependent augmentation of vector production. Furthermore, the neuraminidase activity necessary for particle release from producer cells could also be incorporated into producer cells by co-expression of influenza NA cDNA. Lentiviral vectors pseudotyped with influenza envelope proteins were able to efficiently transduce via the apical membrane of polarized mouse tracheal cultures in vitro as well as mouse tracheal epithelia in vivo.

Animals↗
PubMed2006

Myasthenia gravis--a rare presentation with tongue atrophy and fasciculation.

We report the case of an unusual presentation of myasthenia gravis with tongue atrophy and fasciculation. Myasthenia gravis is an autoimmune condition associated with weakness and fatigability of voluntary muscles. In >50%, the initial symptoms and signs are related to extraocular muscle weakness, such as diplopia or ptosis [Tsung K, Seggev JS. An unusual cause of dysphagia. West J Med 1995; 163: 159-60]. Rarely, it is known to affect bulbar muscles and can lead to dysphagia and respiratory compromise.

Aged↗
PubMed2006

Childhood cicatricial pemphigoid confined to the vulva.

Cicatricial pemphigoid or benign mucous membrane pemphigoid is an autoimmune bullous disease predominantly affecting the mucosal surfaces and healing with scar formation. Localized cicatricial pemphigoid of the vulva in children is rare. We present a child with this rare condition who was initially investigated on suspicion of her being subjected to child sexual abuse, and discuss its management.

Administration, Topical↗
PubMed2006

Factors predicting outcome of vitrectomy for diabetic macular oedema: results of a prospective study.

AIM: To determine preoperative demographic, clinical, and optical coherence tomography (OCT) factors which might predict the visual and anatomical outcome at 1 year in patients undergoing vitrectomy and inner limiting membrane peel for diabetic macular oedema (DMO). METHODS: A prospective, interventional case series of 33 patients who completed 1 year follow up. Measurements were taken preoperatively and at 1 year. Outcome measures were logMAR visual acuity (VA) and OCT macular thickness. A priori explanatory variables included baseline presence of clinical and/or OCT signs suggesting macular traction, grade of diabetic maculopathy, posterior vitreous detachment, fluorescein leakage and ischaemia on angiography, presence of subretinal fluid, and peroperative indocyanine green (ICG) use. RESULTS: 33 patients completed 1 year follow up. On average VA deteriorated by 0.035 logMAR (p = 0.40). Macular thickness significantly improved by a mean of 139 microm (95% CI; 211 to 67, p<0.001). Patients with evidence of clinical and/or OCT macular traction significantly improved logMAR acuity (logMAR improvement = 0.08) compared with patients without traction (logMAR deterioration 0.11, p = 0.01). Presence of subretinal fluid significantly predicted worse postoperative result (p = 0.01) CONCLUSION: On average, patients showed a statistically significant improvement in central macular thickness following treatment but a marginal acuity worsening. Presence of subretinal fluid on OCT is hypothesised to be exudative rather than tractional in nature. The visual benefit of vitrectomy for DMO in this study was limited to patients who exhibit signs of macular traction either clinically and/or on OCT.

Aged↗
PubMed2006

Delivering results to clients: a question of satisfying needs or desires?

Demand for genitourinary (GU) medicine services is outstripping supply. Improving efficiency can modulate the supply side of the equation, e.g. decreasing the number of clients having to return for their results. This survey explored how clients at two central London GU medicine clinics would like to receive their results and their views were reflected against what was offered by London GU medicine clinics. There was a significant difference between the result delivery services that the clients wanted and what the clinics provided (P <0.0001, chi(2)). Of the clients, 92% wanted to know their results regardless of outcome whereas 22% of London clinics would only inform clients of positive results. This study questions the importance and feasibility of patient choice, an important aspect of the National Strategy for Sexual Health and HIV. Clinics may not individually be able to provide choice but between them, they do provide a wide range of alternatives for the client.

HIV Infections↗
PubMed2005

Multidetector spiral CT renal angiography in the diagnosis of giant renal artery aneurysms.

A case of giant renal artery aneurysm in a 63-year-old man is presented. Renal artery aneurysms are rare (incidence < 1%) and this case is one of the largest giant renal artery aneurysms recorded in the literature. This case also demonstrates the value of multidetector spiral computed tomographic renal angiography in the diagnosis, planning, and treatment of renal aneurysms.

Aneurysm↗
PubMed2005

The anatomy of the dorsal cutaneous branch of the ulnar nerve - a safe zone for positioning of the 6R portal in wrist arthroscopy.

The dorsal branch of the ulnar nerve passes close to the 6 Radial portal used in wrist arthroscopy. We examined 20 cadaveric limbs to establish the course of this nerve. We found it consistently crossed a line between the ulnar styloid and the fourth web space at an average of 2.4 cm from the ulnar styloid (range 1.8-2.8 cm). This represented 23% (+/- 2.5 STD range 19-27%) of the distance from the styloid process to the fourth web space. Recommendations are made to help avoid iatrogenic injury to the nerve during arthroscopy. The literature on the anatomy of this nerve and its variations and the clinical relevance of this knowledge are discussed.

Arm↗
PubMed2005

Polysaccharide vaccines for preventing serogroup A meningococcal meningitis.

BACKGROUND: Randomised trials carried out over two decades ago showed that the polysaccharide vaccine prevented serogroup A meningococcal meningitis. Subsequent non-randomised studies, however, suggested significant variations in the age-specific duration of protection among young children. OBJECTIVES: The aim of the review was to determine the effect of polysaccharide serogroup A vaccine for preventing serogroup A meningococcal meningitis. The specific objectives were to assess the age-specific effects of the vaccine, the effect of booster doses in children under five years of age, and the duration of protection in children and adults. SEARCH STRATEGY: In 2004, the review was updated. The following databases were searched for records of new trials: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004); MEDLINE (January 1966 to November Week 1 2004); and EMBASE (January 1990 to September 2004). SELECTION CRITERIA: The first stage of the review included randomised trials. The second stage included non- randomised studies that addressed specific outcomes not answered by the randomised trials. DATA COLLECTION AND ANALYSIS: One reviewer assessed the methodological quality of the randomised trials and two reviewers independently identified and assessed the non-randomised studies. Of the twelve eligible Randomized trials, four were excluded because of the high risk of bias in assessing vaccine efficacy. Data from the trials were pooled using the Exact method to assess vaccine efficacy at one, two and three years post vaccination. Of the 15 non-randomised studies, only two addressed the specific objectives not answered by the randomised trials but were assessed to be at high risk of bias. MAIN RESULTS: The protective effect within the first year of vaccination was consistent across the randomised trials, and the summary vaccine efficacy was 95% (95% confidence interval (CI) 87% to 99%). Protection extended into the second and third year after vaccination but the results did not attain statistical significance. The vaccine was protective in Finnish children aged 3 months to five years. The latter was also the only trial that assessed the effect of a booster dose in children under two years of age but lacked power to yield statistically significant results. The vaccine was protective in one- to five-year old children in developing countries (Nigeria and Sudan) but the age-specific efficacy in strata between one and five years of age could not be determined. AUTHORS' CONCLUSIONS: For the first year after vaccination, the polysaccharide serogroup A vaccine was strongly protective against serogroup A meningococcal meningitis in participants over five years of age. It was also protective beyond the first year after vaccination in this age group but the level of vaccine efficacy could not be determined with precision. Children aged one to five years in developing countries were also protected but the level of efficacy in this age group could not be determined. While the vaccine was strongly protective among children aged three months to five years in developed countries the level of efficacy across age strata within this age group could not be determined. The number of children aged under two years was too small to draw conclusions on the protective effect of a booster dose of vaccine.

Humans↗
PubMed2005

Fine mapping of the X-linked split-hand/split-foot malformation (SHFM2) locus to a 5.1-Mb region on Xq26.3 and analysis of candidate genes.

Split-hand/split-foot malformation (SHFM) is a genetically heterogeneous disorder, with five known loci, that causes a lack of median digital rays, syndactyly, and aplasia or hypoplasia of the phalanges, metacarpals, and metatarsals. In the only known SHFM2 family, affected males and homozygous females exhibit monodactyly or bidactyly of the hands and lobster-claw feet. This family (1) was revisited to include additional subjects and genealogical data. All 39 affected males and three females fully expressed the SHFM, while 13 carrier females examined exhibited partial expression of SHFM. We narrowed the previously linked 22-Mb genetic interval on Xq24-q26 (2), by analyzing additional family members and typing additional markers. The results define a 5.1-Mb region with a new centromeric boundary at DXS1114 and a telomeric boundary at DXS1192. We did not identify mutations in the exons and exon/intron boundaries of 19 candidate genes. These data suggest that the mutation may lie in a regulatory region of one of these candidate genes or in another gene within the SHFM2 region with unclear role in limb development.

Abnormalities, Multiple↗
PubMed2005

Metallic stents in large bowel obstruction: experience in a District General Hospital.

INTRODUCTION: Metallic stents are used increasingly in the palliation of malignant large bowel obstruction. Stenting has also been used in the setting of acute obstruction, allowing appropriate patient preparation for an elective colectomy. METHODS: Uncovered metallic stents were inserted using a combined endoscopic/radiological technique in patients presenting with large bowel obstruction. RESULTS: Seventeen patients (10 female, mean age 75.2 years) presented with large bowel obstruction, 14 due to malignancy and 3 secondary to diverticular stricture. Technical success was achieved in 13/17 with clinical success in 12 of these 13. There were no perforations or procedure related deaths. One stented patient had elective surgery. The five patients with clinical/technical failure required emergency surgery. CONCLUSION: The result of our preliminary experience in the use of metallic stents is encouraging. Metallic stents should be available in all hospitals as part of a multimodality approach in treating large bowel obstruction.

Adult↗
PubMed2005

Ocular morbidity and fuel use: an experience from India.

The association of fuel use and ocular morbidity in a village in western India was investigated in a cross sectional prevalence survey involving 469 randomly selected subjects. All subjects were interviewed and underwent medical and ophthalmological examination. Wood use was found to be an important factor in the aetiology of age dependent cataract (OR 2.12, 95% CI 1.03-4.34). When comparing wood only and LPG only users, the odds ratio was 3.47 (95% CI 1.05-11.50). In cases of eye irritation, coal use (OR 2.04, 95% CI 1.13-3.68) and cattle dung use (OR 1.83, 95% CI 1.35-2.47) were shown to be important factors, while male sex posed a lesser risk.

Adult↗
PubMed2005

Fibrogenesis in the pancreas after acinar cell injury.

Fibrosis within the pancreas is a key feature of chronic pancreatitis and pancreatic cancer. It has now been well demonstrated that following injury to acinar cells, pancreatic stellate cell activation, migration and proliferation is the key mediator of this process. Many cytokines and growth factors have been studied, particularly TGF-beta, which appears to be the major stimulus to fibrinogenesis. There is current interest in the mechanisms of phenotypic change between the active and quiescent forms, apoptosis and the signalling pathways that may be involved. The pancreatic stellate cell is likely to play an important role in maintaining the normal extracellular matrix; we speculate that the dysregulation of this process is an important factor in chronic pancreatitis.

Apoptosis↗