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Biomedical subjects

A Parikh

Publications and source records attributed to A Parikh.

At least 19 recordsLinked to original sources

Measurement of the Ec.m. = 184 keV resonance strength in the 26gAl (p, gamma)27 Si reaction.

The strength of the Ec.m. = 184 keV resonance in the 26gAl(p, gamma)27 reaction has been measured in inverse kinematics using the DRAGON recoil separator at TRIUMF's ISAC facility. We measure a value of omega gamma = 35 +/- 7 microeV and a resonance energy of Ec.m. = 184 +/- 1 keV, consistent with p-wave proton capture into the 7652(3) keV state in 27Si, and discuss the implications of these values for 26GAl nucleosynthesis in typical oxygen-neon white-dwarf novae.

Journal Article↗

Revision of cemented hip arthroplasty using a hydroxyapatite-ceramic-coated femoral component.

We report the clinical and radiological outcome of 86 revisions of cemented hip arthroplasties using JRI-Furlong hydroxyapatite-ceramic-coated acetabular and femoral components. The acetabular component was revised in 62 hips and the femoral component in all hips. The mean follow-up was 12.6 years and no patient was lost to follow-up. The mean age of the patients was 71.2 years. The mean Harris hip and Oxford scores were 82 (59 to 96) and 23.4 (14 to 40), respectively. The mean Charnley modification of the Merle d'Aubigné and Postel score was 5 (3 to 6) for pain, 4.9 (3 to 6) for movement and 4.4 (3 to 6) for mobility. Migration of the acetabular component was seen in two hips and the mean acetabular inclination was 42.6 degrees. The mean linear polyethylene wear was 0.05 mm/year. The mean subsidence of the femoral component was 1.9 mm and stress shielding was seen in 23 (28%) with bony ingrowth in 76 (94%). Heterotopic ossification was seen in 12 hips (15%). There were three re-revisions, two for deep sepsis and one for recurrent dislocation and there were no re-revisions for aseptic loosening. The mean EuroQol EQ-5D description scores and health thermometer scores were 0.69 (0.51 to 0.89) and 79 (54 to 95), respectively. With an end-point of definite or probable loosening, the probability of survival at 12 years was 93.9% and 95.6% for the acetabular and femoral components, respectively. Overall survival at 12 years, with removal or further revision of either component for any reason as the end-point, was 92.3%. Our study supports the continued use of this arthroplasty and documents the durability of hydroxyapatite-ceramic-coated components.

Aged↗

Is the nuclear spin-orbit interaction changing with neutron excess?

The difference in the energies of the lowest states corresponding to the two nodeless single-particle orbitals outside the Z=50 closed proton shell, h(11/2) and g(7/2), increases with neutron excess. We have measured the Sn(alpha,t) reaction for all seven stable even Sn isotopes and found that the spectroscopic factors are constant for these two states, confirming their characterization as single-particle states. The trend in energies is consistent with a decrease in the nuclear spin-orbit interaction. A similar trend, also suggesting a decreasing spin-orbit splitting, is seen in the energies of the neutron single-particle states outside the N=82 core, i(13/2) and h(9/2).

Journal Article↗

Genotype-phenotype correlation in a family with Arg135Leu rhodopsin retinitis pigmentosa.

AIM: To describe the clinical characteristics and disease course of a large family with retinitis pigmentosa (RP) from an Arg135Leu change in rhodopsin. METHODS: 29 patients in this family were evaluated. Goldmann visual fields were performed on 14 affected individuals, Ganzfeld electroretinography (ERG) on eight individuals (11-56 years), and blood samples collected on 10 individuals (11-58 years). Patient visual field data were compared with previously reported patients with different rhodopsin mutations using linear regression. RESULTS: An Arg135Leu mutation was identified in rhodopsin. Distinct stages of clinical evolution were identified for this family ranging from normal, white dots, classic bone spicules and, finally, ending with extensive retinal pigment epithelium (RPE) atrophy. 9/16 patients over the age of 20 years also demonstrated marked macular atrophy. All patients who underwent full field ERG testing demonstrated non-recordable ERGs. The overall regression model comparing solid angles of visual fields from patients with rhodopsin mutations (Pro23His, Pro347Ala, Arg135Leu) shows significant effects for age (p = 0.0005), mutation (p = 0.0014), and interaction between age and mutation (p = 0.018) with an R(2) of 0.407. CONCLUSIONS: An Arg135Leu change in rhodopsin results in a severe form of RP that evolves through various fundus appearances that include white dots early in life and classic appearing RP later. This transmembrane change in rhodopsin proves to be more severe than in a family with an intradiscal change and a family with a cytoplasmic change.

Adolescent↗

[Oral and extraoral disease due to betel nut chewing].

BACKGROUND AND OBJECTIVE: Betel chewing is common in India and southeast Asia. It shows mild psychostimulatory effects but with prolonged use there is a risk of oral and extraoral disease. Surprisingly, betel nut associated disorders are rarely discussed in the dermatological literature. METHODS: A review about betel nut associated disease is given based on a literature review and our own experiences. RESULTS: Both benign and malignant diseases can be induced by betel nut chewing. Betel causes reddish discoloration of teeth, periodontitis and buccal mucositis. Submucous fibrosis is a precancerous disease that may eventually develop into oral squamous cell cancer (OSCC). Among malignant diseases induced by betel quid, OSCC is the most important but esophageal cancer and hepatocellular cancer can also be observed. The available treatments are of limited value. CONCLUSIONS: Betel nut chewing has its own morbidity and mortality due to the induction of benign and malignant diseases. There is a lack of controlled trials although both betel nut chewing and the associated diseases are common.

Areca↗

Effects of non-steroidal anti-inflammatory drugs on cyclo-oxygenase and lipoxygenase activity in whole blood from aspirin-sensitive asthmatics vs healthy donors.

1. Cyclo-oxygenase (COX) and lipoxygenase (LO) share a common substrate, arachidonic acid. Aspirin and related drugs inhibit COX activity. In a subset of patients with asthma aspirin induces clinical symptoms associated with increased levels of certain LO products, a phenomenon known as aspirin-sensitive asthma. The pharmacological pathways regulating such responses are not known. 2. Here COX-1 and LO activity were measured respectively by the formation of thromboxane B(2) (TXB(2)) or leukotrienes (LT) C(4), D(4) and E(4) in whole blood stimulated with A23187. COX-2 activity was measured by the formation of prostaglandin E(2) (PGE(2)) in blood stimulated with lipopolysaccharide (LPS) for 18 h. 3. No differences in the levels of COX-1, COX-2 or LO products or the potency of drugs were found in blood from aspirin sensitive vs aspirin tolerant patients. Aspirin, indomethacin and nimesulide inhibited COX-1 activity, without altering LO activity. Indomethacin, nimesulide and the COX-2 selective inhibitor DFP [5,5-dimethyl-3-(2-isopropoxy)-4-(4-methanesulfonylphenyl)-2(5H)-furanone] inhibited COX-2 activity. NO-aspirin, like aspirin inhibited COX-1 activity in blood from both groups. However, NO-aspirin also reduced LO activity in the blood from both patient groups. Sodium salicylate was an ineffective inhibitor of COX-1, COX-2 or LO activity in blood from both aspirin-sensitive and tolerant patients. 4. Thus, when COX activity in the blood of aspirin-sensitive asthmatics is blocked there is no associated increase in LO products. Moreover, NO-aspirin, unlike other NSAIDs tested, inhibited LO activity in the blood from both aspirin sensitive and aspirin tolerant individuals. This suggests that NO-aspirin may be better tolerated than aspirin by aspirin-sensitive asthmatics.

Anti-Inflammatory Agents, Non-Steroidal↗

Paradoxical low nasal nitric oxide in nasal polyposis.

BACKGROUND: Nitric oxide (NO) is synthesized in the respiratory tract. Three isoforms of NO synthase have been described in man, with the inducible form related to inflammatory disease. In the paranasal sinuses constitutive production of nitric oxide has been demonstrated, with levels of 20-25 p.p.m. being found in sinus puncture. Nasal polyposis is a chronic inflammatory condition in which inducible nitric oxide synthase (iNOS) expression is elevated in nasal polyp epithelium. OBJECTIVES: 1. Measurement of upper airway nitric oxide in nasal polyposis patients compared with those with allergic rhinitis, and with normal controls. 2. To assess the effect of polyp treatment on nasal NO levels. METHODS: NO levels (parts per billion) were measured in nasal and pulmonary exhaled air using a LR 2000 Logan Sinclair nitric oxide gas analyser. This utilizes the chemiluminescence principle. Eighty-two patients were studied: 44 with rhinitis, but without polyps, and 38 with nasal polyps. NO levels were compared with those of 20 normal controls. In 23 further polyp patients, levels were measured pre- and post-treatment and the changes were compared with alterations in polyp size, as assessed by rigid nasendoscopy. RESULTS: Nasal NO levels were significantly lower (Kruskal-Wallis, P = 0.000, chi2 = 27.5, d.f. = 3) in patients with polyps than those found in uncomplicated allergic rhinitis. NO levels were correlated directly with extent of polyposis as graded by the Lund-McKay index. Successful treatment, with reduction in polyp volume, was associated with a rise in NO levels (P = 0.042). CONCLUSION: NO levels are low in nasal polyposis, despite high levels of iNOS, possibly related to blockage of the ostiomeatal complex and failure of NO generated constitutively in the sinuses to reach the nasal airway. A rise in the NO levels is seen with successful polyp treatment, and is proportional to the reduction in endoscopically assessed polyp size, suggesting that with both medical and surgical therapy, the ostiomeatal complex obstruction is decreasing. We propose the following scenario. Nasal NO levels are the result of two processes: inducible NO production by inflamed nasal mucosa plus constitutive sinus mucosal production, detectable in normals. In uncomplicated allergic rhinitis with patent sinus ostia NO levels tend to be elevated, but when inflammation is sufficient to obstruct sinus ostia (as in nasal polyps), NO levels fall because sinus NO makes the major contribution.

Adult↗

High levels of nitric oxide synthase activity are associated with nasal polyp tissue from aspirin-sensitive asthmatics.

The pathogenesis of aspirin intolerance remains unclear. Inducible nitric oxide synthase (iNOS) expression is upregulated in nasal polyp epithelium, implying a role for nitric oxide (NO) in its formation. We decided to compare iNOS activity in polyp tissue from patients with and without aspirin intolerance. Nasal polyp tissue was collected from 15 patients undergoing routine nasal polypectomy. These patients were classified into three groups: Group A comprised patients with nasal polyps without asthma; Group B contained patients with nasal polyps and asthma; and Group C comprised patients with nasal polyps, asthma and aspirin sensitivity. All subjects in Group C had a history of aspirin-induced reaction and a confirmatory intranasal challenge with lysine-aspirin. NOS activity was measured by the ability of tissue homogenates to convert 3,4-L-arginine to L-citrulline in an L-N(G)-nitro-L-arginine-inhibitable fashion. The iNOS activity (picomoles) in polyp tissue from the 3 groups was: A, 248.72+/-220.79; B, 23.71+/-41.06; and C, 549.71+/-132.11. Thus, nasal polyps from patients with Samter's triad had a significantly higher iNOS activity (p = 0.004; one-way ANOVA). This finding does not correlate simply with disease severity or with the occurrence of asthma and could indicate another important facet of aspirin-induced airways disease.

Adult↗

Therapeutic implications of enhanced G(0)/G(1) checkpoint control induced by coculture of prostate cancer cells with osteoblasts.

Osteoblastic metastases are common in lethal prostate cancer. Effective therapy for bone metastases is lacking. Thus, developing an appropriate in vitro screening system is critical to prioritize which of the newly developed agents should undergo additional expensive and time-consuming in vivo evaluation in bone metastases animal models. In the past, such in vitro screening evaluated the response of prostate cancer cells to chemotherapeutic agents in monoculture without the presence of osteoblasts. In such monoculture, prostate cancer cells have a high (i.e., >90%) proliferative growth fraction. In contrast, the growth fraction (i.e., mean: 7.1 +/- 0.8%; median: 3.1%) in 117 metastatic sites of prostate cancer obtained from 11 androgen ablation failing patients at "warm" autopsy was found to be >10-fold lower. To better mimic the lower growth fraction observed clinically, LNCaP human prostate cancer cells were cocultured with membrane-separated hFOB human osteoblasts. Such coculturing significantly lowered the growth fraction of the LNCaP cells (i.e., from >90 to <30%) without enhancing their low rate (i.e., <5%) of apoptosis. This lowering of the growth fraction was documented using flow cytometry, Ki-67 immunohistochemistry, and 5-bromo-2-deoxyuridine incorporation. Using RNase protection assays, it was documented that coculture with osteoblasts causes enhanced p53, p27, and p21 expression leading to a decrease in the number of LNCaP cells entering the cell cycle (i.e., enhanced number of LNCaP cells in G(0)-G(1) and a decrease in S and G(2)-M and thus the growth fraction). This osteoblast-induced enhanced G(0)-G(1) checkpoint control affected the chemosensitivity of LNCaP cells. This was documented by coculturing LNCaP cells with hFOB cells to condition the medium for 3 days to lower the growth fraction to <30% before exposing the LNCaP cells for 48 h to various concentrations of Taxol, doxorubicin, or thapsigargin (TG). In standard high (i.e., >90%) growth fraction cultures (i.e., cultures in the absence of osteoblast-conditioned medium), there was a dose-dependent and significant (P < 0.05) increase in apoptosis of LNCaP cells exposed to Taxol or doxorubicin. In contrast, even the highest dose of Taxol (1 microM) did not enhance apoptosis of lower growth fraction LNCaP cells cultured in osteoblast-conditioned medium. Similarly, only the highest concentration of doxorubicin (1 microM) enhanced apoptosis in lower growth fraction cells. In contrast, 100 nM TG induced high levels of apoptosis in both lower and high-growth fraction LNCaP cultures. These results demonstrate that the osteoblast/LNCaP coculture system is a better in vitro screen than monoculture to identify proliferation-independent agents for the treatment of prostate cancer bone metastases, and TG is such an agent.

Antineoplastic Agents↗

Clonogenic analysis reveals reserve stem cells in postnatal mammals: I. Pluripotent mesenchymal stem cells.

Clonal populations of lineage-uncommitted pluripotent mesenchymal stem cells have been identified in prenatal avians and rodents. These cells reside in the connective tissue matrices of many organs and tissues. They demonstrate extended capabilities for self-renewal and the ability to differentiate into multiple separate tissues within the mesodermal germ line. This study was designed to determine whether such cells are present in the connective tissues of postnatal mammals. This report describes a cell clone derived by isolation from postnatal rat connective tissues, cryopreservation, extended propagation, and serial dilution clonogenic analysis. In the undifferentiated state, this clone demonstrates a high nuclear-to-cytoplasmic ratio and extended capacity for self-renewal. Subsequent morphological, histochemical, and immunochemical analysis after the induction of differentiation revealed phenotypic markers characteristic of multiple cell types of mesodermal origin, such as skeletal muscle, smooth muscle, fat cells, cartilage, and bone. These results indicate that this clone consists of pluripotent mesenchymal stem cells. This report demonstrates that clonal populations of reserve stem cells are present in mammals after birth. Potential roles for such cells in the maintenance, repair, and regeneration of mesodermal tissues are discussed.

Animals↗

The prevalence of atopic disorders in children with chronic otitis media with effusion.

We studied 209 children, referred to a multi-disciplinary 'Glue ear/Allergy' clinic at our hospital with a history of chronic or recurrent otitis media with effusion (OME), in order to determine the prevalence of atopic disease in this population. Referrals were made either from within the hospital by Ear, Nose and Throat (ENT) Surgeons and Audiological Physicians (internal), or by General Practitioners (external). Assessment of atopic status was based on medical history, physical examination, nasal smears and skin-prick testing (SPT) in all children; and on blood eosinophil counts and total immunoglobulin E (IgE) levels in a randomly selected subset. The main outcome measures were number of children with rhinitis, asthma, eczema, positive SPT, raised IgE level (> 100 IU/l), and nasal and blood eosinophilia. We found allergic rhinitis in 89%, asthma in 36%, and eczema in 24%. SPTs were positive to one or more of eight common inhalant aeroallergens in 57% of children. Blood tests in the selected subset revealed eosinophilia in 40% and a raised serum IgE in 28%. The worldwide prevalence of allergic rhinitis in children has been estimated to be 20%. The 89% prevalence found in this study is very high and there are a number of reasons which suggest that there may be a causal relationship. Whole-population studies will be required to confirm these findings, which could have important therapeutic implications for OME.

Allergens↗

An open audit of montelukast, a leukotriene receptor antagonist, in nasal polyposis associated with asthma.

BACKGROUND: Nasal polyposis occurs frequently in patients with intrinsic asthma, especially in those who are aspirin sensitive. It can be difficult to treat effectively, even with surgery and regular topical intranasal corticosteroids many patients are still symptomatic. OBJECTIVE: To investigate the response to montelukast, a leukotriene D4 receptor antagonist, as an add-on therapy to topical and inhaled corticosteroids in patients, both aspirin sensitive (AS) and aspirin tolerant (AT), with nasal polyposis and asthma. METHODS: Nasal polyposis symptoms were assessed by visual analogue scales; nasal polyps were assessed by nasendoscopy and via the measurement of nasal volumes by acoustic rhinometry. The nasal airway was assessed by nasal inspiratory peakflow (NIPF). Asthma was monitored using symptom scores and peak expiratory flow measurements. Aspirin sensitivity was assessed by history together with intranasal lysine aspirin challenge. Upper and lower airway nitric oxide measurements were made before and during treatment. RESULTS: Clinical subjective improvement in nasal polyposis occurred in 64% AT (P < 0.01), patients and 50% AS patients (P > 0.05); asthma improvement in 87% AT and 61% AS patients (P < 0.05 for both). Objective changes in peak flow occurred only in AT patients (P < 0.05). Acoustic rhinometry, nasal inspiratory peak flow and nitric oxide levels did not change significantly in any group, however, correlations were seen between nitric oxide levels and polyp scores and between nitric oxide levels and acoustic rhinometry changes. Improvement on montelukast therapy was not associated with any of the following variables: age, sex, skin prick test positivity, disease duration or aspirin sensitivity. (P > 0.05 for all). CONCLUSION: The findings are consistent with a subgroup of nasal polyps/asthma patients in whom leukotriene receptor antagonists are effective. This is not related to aspirin sensitivity. Further placebo-controlled studies need to be undertaken.

Acetates↗

Student feedback in problem based learning: a survey of 103 final year students across five Ontario medical schools.

CONTEXT: Problem based learning (PBL) has become an integral component of medical curricula around the world. In Ontario, Canada, PBL has been implemented in all five Ontario medical schools for several years. Although proper and timely feedback is an essential component of medical education, the types of feedback that students receive in PBL have not been systematically investigated. OBJECTIVES: In the first multischool study of PBL in Canada, we sought to determine the types of feedback (grades, written comments, group feedback from tutor, individual feedback from tutor, peer feedback, self-assessment, no feedback) that students receive as well as their satisfaction with these different feedback modalities. SUBJECTS AND METHODS: We surveyed a sample of 103 final year medical students at the five Ontario schools (University of Toronto, McMaster University, Queens University, University of Ottawa and University of Western Ontario). Subjects were recruited via E-mail and were asked to fill out a questionnaire. RESULTS: Many students felt that the most helpful type of feedback in PBL was individual feedback from the tutor, and indeed, individual feedback was one of the more common types of feedback provided. However, although students also indicated a strong preference for peer and group feedback, these forms of feedback were not widely reported. There were significant differences between schools in the use of grades, written comments, self-assessment and peer feedback, as well as the immediacy of the feedback given. CONCLUSIONS: Across Ontario, students do receive frequent feedback in PBL. However, significant differences exist in the types of feedback students receive, as well as the timing. Although rated highly by students at all schools, the use of peer feedback and self-assessment is limited at most, but not all, medical schools.

Curriculum↗

Fecal occult blood testing in a noncompliant inner city minority population: increased compliance and adherence to screening procedures without loss of test sensitivity using stool obtained at the time of in-office rectal examination.

OBJECTIVES: Fecal occult blood screening is cost-effective, is easily administered to large groups of patients, and reduces mortality associated with colorectal cancer. Within our predominant African American and Latino inner city clinic populations, compliance with common screening procedures is suboptimal. A procedure with increased compliance is needed to adequately screen this population at high risk for colorectal cancer. The objective of this study was to compare the results of the 3-day at-home hemoccult test for occult blood to those of a hemoccult test performed from stool obtained at rectal examination in the office. METHODS: A total of 350 consecutive patients referred to the GI clinic of University Hospital or Jersey City Medical Center for colorectal cancer screening had both the 3-day at-home hemoccult test and an in-office hemoccult examination performed, followed by either sigmoidoscopy (for negative results) or by colonoscopy (for positive results). RESULTS: Patients were noncompliant with dietary restrictions, 3-day card return, follow-up appointments, and endoscopy with conventional screening methods. Decisions based on the in-office examination with direct scheduling of endoscopy significantly improved compliance with follow-up. There was no statistical difference between the two detection methods, suggesting that the in-office examination was the more effective screening test. CONCLUSIONS: Endoscopy based on an in-office hemoccult examination is an acceptable alternative to using the 3-day at-home stool collection to govern endoscopic choices. In a noncompliant inner city population, use of the in-office examination increased compliance with follow up, potentially allowing more patients exposure to screening.

Black or African American↗

Topical corticosteroids in chronic rhinosinusitis: a randomized, double-blind, placebo-controlled trial using fluticasone propionate aqueous nasal spray.

Chronic rhinosinusitis (CRS) is a recalcitrant inflammatory process which has a marked detrimental impact on quality of life. At the present there is no cure for this condition, measures are taken to stop progression, and provide symptomatic relief. Topical corticosteroids are commonly prescribed in the management of CRS, but few trials show effectiveness in clinical settings. We set up a randomized, double-blind, placebo-controlled trial to study the effectiveness of a topical corticosteroid agent--fluticasone propionate aqueous nasal spray (FPANS) in patients with CRS. We measured symptoms, diary card, and rigid endoscopy scores, acoustic rhinometry, middle meatal swabs, blood tests--CRP, ESR, WBC, and eosinophil count. Measurements were done at the start of the trial, at 8 weeks, and 16 weeks where possible. Twenty-two patients completed the trial, 9 received FPANS, and 13 had placebo. There was no difference between the 2 groups on all counts. When patients were considered as one group, there was an improvement in the diary card scores (p = 0.054), comparing baseline to 8 or 16 weeks. There was no evidence that the regular use of topical corticosteroid increased the risk of developing an infection. An important observation was that the topical corticosteroid did not precipitate acute sinusitis. There is compelling evidence that topical corticosteroids down-regulate cytokine expression, and it is likely that a larger, and longer multi-centre trial may prove their efficacy in CRS.

Administration, Intranasal↗