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Biomedical subjects

M Jain

Publications and source records attributed to M Jain.

At least 73 records · Page 4Linked to original sources

Cervical thymic cyst: report of a case and review of the literature.

Congenital thymic cysts are uncommon and often misdiagnosed as either branchial cleft or cystic hygromas. This paper presents the case of a male child, who presented with a soft, fluctuating mass in the left side of his neck. Surgical excision revealed an ectopic thymic cyst. The histopathologic features of thymic cysts are diagnostic. Ectopic thymic tissue may be an infrequent finding, but it should be included in the differential diagnosis of neck masses, especially in children.

Child, Preschool↗

Galpha(i2) but not Galpha(i3) is required for muscarinic inhibition of contractility and calcium currents in adult cardiomyocytes.

Parasympathetic stimulation of the heart acts through M(2)-muscarinic acetylcholine receptors to regulate ion channel activity and subsequent inotropic status. Although muscarinic signal transduction is mediated via pertussis toxin-sensitive G proteins Galpha(i/o), the specific signal transduction requirements of Galpha(i2) and Galpha(i3) in mediating muscarinic regulated L-type calcium currents (I(Ca, L)), intracellular calcium, and cell contractility remain to be determined. Adult ventricular myocytes were isolated from Galpha(i2)-null mice, Galpha(i3)-null mice, and their wild-type littermates. Cell shortening, intracellular calcium levels, and I(Ca, L) were all measured in response to isoproterenol, a beta-adrenergic receptor agonist, and carbachol, a cholinergic receptor agonist. With isoproterenol stimulation, myocytes from all groups demonstrated a marked increase in calcium currents, correlating with augmented intracellular calcium transient amplitude and cell shortening. Carbachol significantly attenuated the isoproterenol response in wild-type and Galpha(i3)-null cells but had no effect in Galpha(i2)-null cells. This study demonstrates that Galpha(i2), but not Galpha(i3), is required for muscarinic inhibition of the beta-adrenergic response in adult murine ventricular myocytes.

Adrenergic beta-Agonists↗

Cytological features of chondroblastoma: a case report with review of the literature.

Chondroblastoma is an uncommon benign tumor of bone with a characteristic epiphyseal location. This report documents the cytological features on fine-needle aspiration biopsy (FNAB) of a chondroblastoma which appeared as a lytic lesion, predominantly in the metaphysis of the medial condyle of right femur in a 20-year-old male. Smears characteristically revealed hyper- to hypocellular lobules comprising small round to polyhedral cells (chondroblasts) embedded in an abundant myxoid stroma. The cytological diagnosis of chondroblastoma was confirmed on histopathology. The radiological appearance and differential diagnosis in this case is discussed.

Adult↗

Idiopathic pulmonary hemosiderosis.

Two cases of idiopathic pulmonary hemosiderosis in children are reported. Both cases presented with a combination of acute/recurrent respiratory symptoms along with iron deficiency anemia. In one case diagnosis was delayed for 18 months after onset of symptoms. After initial stabilisation with corticosteroid therapy, both cases were put on chloroquine therapy and showed improvement. Various other forms of therapy and outcome are discussed. It is suggested that in cases with recurrent respiratory symptoms, idiopathic pulmonary hemosiderosis should also be considered after excluding infectious etiology.

Adrenal Cortex Hormones↗

Early versus late-onset idiopathic focal segmental glomerulosclerosis.

Glomerular diseases in children, although similar in histological appearance to those in adults, may have a better prognosis. There is much controversy regarding the prognostic factors in idiopathic focal segmental glomerulosclerosis (FSGS), especially the comparative prognosis of children and adults. A comparative analysis was carried out of 36 consecutive biopsy-proven cases of idiopathic FSGS presenting early in life ['early onset' as seen in children < or =12 years (group I)] and 36 cases presenting later ['late-onset' as seen in older children >12 years and adults (group II)]. Patients were compared for clinical, biochemical, and histopathological features, as well as disease outcome. A significantly higher prevalence of hypertension (P=0.002) and microscopic hematuria was seen in group II (P=0.02). There were no differences between the two groups in glomerular filtration rates corrected for body surface area at initial presentation (92+/-11 ml/min/1.73 m2 vs. 94+/-14 ml/min/1.73 m2). Patients with 'late-onset' FSGS had a significantly higher number of glomeruli with segmental sclerosis (P=0.007), more mesangial matrix expansion (P=0.009), greater mesangial cellularity (P=0.003), and significantly higher blood vessel involvement (P=0.03) than those with 'early onset' FSGS. There was a significantly higher response to steroids in group I (82.3%) than group II (36.4%) (P<0.02). At the end of the study period, 2 patients in group I and 11 in group II had developed persistent renal failure (P=0.01). Thus 'early onset' FSGS is more common in males, has significantly lower prevalence of hypertension and microscopic hematuria, with less-severe histopathological involvement, is more often steroid responsive, and has a better prognosis than 'late-onset' FSGS.

Adolescent↗

Effects of systemic 3-nitropropionic acid-induced lesions of the dorsal striatum on cannabinoid and mu-opioid receptor binding in the basal ganglia.

Systemic administration of 3-nitropropionic acid (3NPA) in experimental animals produces bilateral striatal lesions similar to those seen in Huntington's disease (HD) caudate and putamen. 3H[-CP55,940 binding to cannabinoid receptors in human basal ganglia nuclei has been shown to be highly susceptible to the earliest pathological changes in the HD brain. In this study, to assess further the suitability of 3NPA-induced striatal lesions as a model for HD neuropathology, we examined the effects of striatal lesions induced by the systemic administration of 3NPA on the binding of 3H[-CP55,940 to pre- and postsynaptic cannabinoid receptors in striatum, globus pallidus, entopeduncular nucleus and substantia nigra pars reticulata and also the effect of 3NPA-induced striatal lesions on the binding of 3H[-DAMGO to mu-opioid receptors in striatal striosomes. Systemic administration of 3NPA induced bilateral and symmetrical lesions in dorsolateral striatum. Within the lesion core, 3H[-CP55,940 and 3H[-DAMGO binding density was reduced to background levels. Beyond the immediate borders of the central core of the 3NPA-induced lesion, striatal binding density was not significantly different from that measured in unlesioned rats. 3H[-CP55,940 binding in globus pallidus, entopeduncular nucleus and substantia nigra in 3NPA-lesioned rats was significantly reduced compared to controls, and the individual decreases were similar for each site. However, these reductions were statistically marginal. These data suggest that, while producing striatal lesions which bear some similarity to those seen in HD, the consequences of 3NPA for striatopallidal and striatonigral efferent projections do not reflect the reported neurodegenerative changes seen in the HD brain.

Animals↗

Angiotensin II receptor blockade attenuates the deleterious effects of exercise training on post-MI ventricular remodelling in rats.

OBJECTIVES: The effects of exercise training on LV remodelling following large anterior myocardial infarction (MI) remains controversial. Blockade of the renin-angiotensin system has been shown to prevent ventricular dilation and deleterious remodeling. We therefore tested, in a rat model of chronic MI, whether any potentially deleterious effects of exercise on post-MI remodelling could be ameliorated by angiotensin II receptor blockade. METHODS: Male Wistar rats underwent coronary ligation or sham operation. Treatment with losartan (10 mg/kg/day) began 1 week post-MI and moderate treadmill exercise (25 m/min, 60 min/day, 5 days/week) was initiated 2 weeks post-MI. Systolic and diastolic pressure-volume relationships were measured in isolated, red-cell perfused, isovolumically beating hearts 8 weeks post-MI. Morphometric measurements were performed in trichrome stained cross sections of the heart. Five groups of animals were compared: sham (n=13), control MI (MI; n=11), MI plus losartan (MI-Los; n=13), MI plus exercise (MI-Ex; n=10) and MI plus exercise and losartan (MI-Ex-Los; n=12). RESULTS: Infarct size (% of left ventricle, LV) was similar among the infarcted groups [MI=43+/-4%, MI-Los=49+/-2%, MI-Ex=45+/-1%, MI-Ex-Los=48+/-2% (NS)]. Exercise, losartan and exercise+losartan treatments all attenuated LV dilation post-MI to a similar degree. Exercise training increased LV developed pressure in both untreated and losartan treated hearts (P<0.05 vs. other MI groups). In addition, exercise resulted in additional scar thinning in untreated hearts, while no additional scar thinning was seen in post-infarct hearts receiving both losartan and exercise. CONCLUSIONS: Following large anterior MI, losartan attenuated LV dilation and scar thinning. In untreated animals, exercise decreased dilation, but also contributed to scar thinning. Therefore, exercise concurrent with blockade of the renin-angiotensin system may provide optimal therapeutic benefit following large anterior MI.

Analysis of Variance↗

Validity of nutrient estimates by food frequency questionnaires based either on exact frequencies or categories.

PURPOSE: The study was designed to assess if category-based Food Frequency Questionnaires (FFQ) could be substituted for exact-frequency based questionnaires. METHODS: Nutrient estimates on 203 subjects from Toronto, Canada, derived from recoding an exact frequency based 132 item food frequency questionnaire (E-FFQ) into categories were evaluated for validity against a 7-day food record (FR). RESULTS: Among men, the median Pearson's correlation coefficient (for energy adjusted nutrients) between FR and E-FFQ was 0.53, ranging from 0.26 for thiamin to 0.72 for calcium. The median correlation dropped to a value of 0.40 (range: 0.18 for thiamin to 0. 56 for carbohydrate) when a category-based FFQ (C-FFQ) and FR were compared. Data on women showed a similar pattern; a median correlation of 0.50 from E-FFQ and 0.42 from C-FFQ. CONCLUSIONS: While the results varied with individual nutrients, overall it is concluded that when validated against food records, the use of exact frequencies in FFQs yielded higher correlation coefficients for most nutrients, and slightly better agreement within quartiles of categories than recoded frequency categories.

Adult↗

Equivalence of 2 effective graft-versus-host disease prophylaxis regimens: results of a prospective double-blind randomized trial.

We have previously demonstrated a decrease in the incidence of acute graft-versus-host disease (GVHD) with the addition of methotrexate (MTX) to cyclosporine (CSP) and prednisone (PSE) chemotherapy in patients with leukemia. We have now completed a prospective randomized trial comparing the 3-drug regimen (CSP/MTX/PSE, including 3 doses of MTX) to the standard 2-drug regimen (CSP/MTX, including 4 doses of MTX) to investigate the benefit of PSE used up front for the prevention of acute and chronic GVHD. In the trial, 193 patients were randomized and 186 were included in the final analysis. All patients received a bone marrow graft from a fully histocompatible sibling donor. The preparatory regimen consisted of fractionated total-body irradiation (fTBI) and etoposide in all but 13 patients, who received fTBI and cyclophosphamide. The patients were randomized to receive either CSP/MTX/PSE or CSP/MTX. The 2 groups were well balanced with respect to diagnosis, disease stage, age, donor-recipient sex, and parity. In an intent-to-treat analysis, the incidence of acute GVHD was 18% (95% confidence interval [CI] 12-28) for the CSP/MTX/PSE group compared with 20% (CI 10-26) for the CSP/,MTX group (P = .60), with a median follow up of 2.2 years. Overall survival was 65% for those receiving CSP/MTX/PSE and 72% for those receiving CSP/MTX (P = .10); the relapse rate was 15% for the CSP/MTX/PSE group and 12% for the CSP/MTX group (P = .83). The incidence of chronic GVHD was similar (46% versus 52%; P = .38), with a follow-up of 0.7 to 6.0 years. Of interest, 21 patients went off study due to GVHD (5 in the CSP/MTX/PSE group and 16 in the CSP/MITX group [P = .02]), and 11 patients went off study because of alveolar hemorrhage (3 in the CSP/MTX/PSE group and 8 in the CSP/MTX group [P = .22]). The addition of PSE did not result in a higher incidence of infectious complications, bacterial (66% versus 58%), viral (77% versus 66%), or fungal (20% versus 20%), in those receiving CSP/MTX/PSE versus CSP/MTX, respectively. These data suggest that the addition of PSE was associated with a somewhat lower incidence of early posttransplantation complications but did not have a positive impact on the incidence of acute or chronic GVHD or event-free or overall survival.

Acute Disease↗

Premorbid diet in relation to survival from prostate cancer (Canada).

OBJECTIVES: To examine the associations between prediagnostic energy, fat, and vitamin A intake and survival from prostate cancer. METHODS: Two hundred and seven cases of prostate cancer from Toronto and 201 cases from Vancouver provided diet histories at diagnosis between 1989 and 1992 and were followed for survival from prostate cancer. After exclusions for various reasons, 263 cases (135 from Toronto, 128 from Vancouver) were analyzed in Cox proportional hazards models. RESULTS: Following adjustments for clinical stage, histologic grade, and other factors, significantly lower risks of dying from prostate cancer in the highest compared with the lowest tertiles of monounsaturated fat intakes were observed in each city and in the combined city analyses (combined cities: hazard ratio [HR] = 0.3; 95% confidence interval (CI) = 0.1-0.7). Survival from prostate cancer was significantly better for cases in the highest tertile of energy intake in Toronto (HR = 0.1; CI = 0.01-0.6) in contrast to that in Vancouver where these cases did relatively worse (HR = 2.6; CI = 0.6-10.7). Other nutrients were either not consistently or not significantly associated with prostate cancer survival in the two cities. CONCLUSIONS: This bi-center cohort study observed a consistent and significant inverse association between the premorbid intake of monounsaturated fat and risk of death from prostate cancer. The inconsistent results for energy intake between cities could potentially be attributed to non-respondent bias in Toronto.

Aged↗

Alcohol consumption and risk of breast cancer: a cohort study.

OBJECTIVES: To study the association between alcohol consumption and breast cancer risk. METHODS: A case-cohort analysis was undertaken within the cohort of 56,837 women who were enrolled in the Canadian National Breast Screening Study (NBSS) and who completed a self-administered dietary questionnaire. (The NBSS is a randomized controlled trial of screening for breast cancer in women aged 40-59 at recruitment.) The cohort was recruited between 1980 and 1985, and during follow-up to the end of 1993 a total of 1469 women in the dietary cohort were diagnosed with biopsy-confirmed incident breast cancer. For comparative purposes a subcohort consisting of a random sample of 5681 women was selected from the full dietary cohort. After exclusions for various reasons the analyses were based on 1336 cases and 5238 noncases. RESULTS: When compared to nondrinkers the adjusted incidence rate ratios (95% confidence intervals) for those consuming > 0 and < or = 10 g of alcohol/day, > 10 and < or = 20 g/day, > 20 and < or = 30 g/day, > 30 and < or = 40 g/day, > 40 and < or = 50 g/day, and > 50 g/day were 1.01 (0.84-1.22), 1.16 (0.91-1.47), 1.27 (0.91-1.78), 0.77 (0.51-1.16), 1.00 (0.57-1.75), and 1.70 (0.97-2.98), respectively; the associated p value for the test for trend was 0.351. Similar findings were obtained when analyses were conducted separately in the screened and control arms of the NBSS, in premenopausal and postmenopausal women, for screen-detected and interval-detected breast cancer, and by levels of other breast cancer risk factors. CONCLUSIONS: The results of this study suggest that alcohol consumption might be associated with increased risk of breast cancer at relatively high levels of intake.

Adult↗

Evaluation of free radical status in CSF in childhood meningitis.

The study was undertaken to investigate the possible role of free radicals and antioxidants in childhood meningitis. Sixty children suffering from acute bacterial meningitis (ABM) or tuberculous meningitis (TBM) according to their clinical and laboratory findings were enrolled in the study. The production of superoxide anions (O2.-), hydrogen peroxide (H2O2) and malondialdehyde (MDA) and the activities of xanthine oxidase (XO), superoxide dismutase (SOD) and glutathione peroxidase (GPx) were monitored in the study groups and findings compared with those in 20 age-matched controls. Children with ABM and TBM who died registered significant increases in the production of O2.- and MDA and in the activities of SOD and CPK compared with survivors. The rate of production of oxidants and MDA and the activities of XO, SOD and CPK were of a much higher magnitude in deceased ABM and in ABM survivors than in fatal TBM and survivors, respectively. The abnormalities in most of the biochemical parameters investigated were more marked in the children with ABM than in TBM and controls (p < 0.001). Increased MDA production and creatine phosphokinase (CPK) activity of different magnitudes in the two study groups suggest varying degrees of tissue damage. The alterations observed in 20 children who died (14 from ABM, 6 from TBM) revealed elevated levels of oxidants, antioxidants and toxicity markers, particularly in ABM patients, which suggests the possibility that natural or synthetic antioxidants might prevent disease progression and tissue damage in childhood meningitis.

Antioxidants↗

The natural history of portal hypertensive gastropathy: influence of variceal eradication.

OBJECTIVE: The natural history and likelihood of bleeding from portal hypertensive gastropathy (PHG) present in patients with portal hypertension before endoscopic variceal obliteration may differ from that in patients who develop PHG during or after variceal eradication. METHODS: A total of 967 variceal bleeders who had achieved variceal eradication by endoscopic sclerotherapy in the recent past were prospectively studied. In all, 88 (9.1%) patients (cirrhosis in 54, noncirrhotic portal fibrosis in 18, and extrahepatic portal vein obstruction in 16) had distinct mucosal lesions. PHG alone was present in 78, PHG with gastric antral vascular ectasia (GAVE) in eight, and GAVE alone in two patients. PHG was graded as mild or severe and according to whether present before (group A) or after endoscopic intervention (group B). Patients underwent regular endoscopy at follow-up to see if the PHG was transitory (disappearing within 3 months), persistent (no change), or progressive. Bleeding from PHG lesions was defined as acute or chronic. RESULTS: Twenty-two (26%) patients had PHG before (group A) and 64 (74%) developed PHG after variceal eradication (group B). During a mean follow-up of 25.1 +/- 14.2 months, PHG lesions disappeared in group A in only two patients (9%), but in group B in 28 (44%) patients (p < 0.05). PHG lesions more often progressed in the former as compared to the latter (18% vs 9.4%, p = NS). The incidence of bleeding was higher in group A than group B (32% vs 4.7%, p < 0.02). Bleeding from PHG occurred in 10 patients (11.6%); seven of them were from group A, and all had either progressive (n = 3) or persistent (n = 4) lesions. CONCLUSIONS: PHG developing after variceal eradication is often transitory and less severe. If PHG is pre-existing, endoscopic therapy for varices could worsen the PHG, with a likelihood of bleeding. Such patients may be benefited by concomitant beta-blocker therapy.

Adolescent↗

Progressive left ventricular remodeling and apoptosis late after myocardial infarction in mouse heart.

We tested the hypothesis that left ventricular (LV) remodeling late after myocardial infarction (MI) is associated with myocyte apoptosis in myocardium remote from the infarcted area and is related temporally to LV dilation and contractile dysfunction. One, four, and six months after MI caused by coronary artery ligation, LV volume and contractile function were determined using an isovolumic balloon-in-LV Langendorff technique. Apoptosis and nuclear morphology were determined by terminal deoxynucleotidyl transferase-mediated nick end-labeling (TUNEL) and Hoechst 33258 staining. Progressive LV dilation 1-6 mo post-MI was associated with reduced peak LV developed pressure (LVDP). In myocardium remote from the infarct, there was increased wall thickness and expression of atrial natriuretic peptide mRNA consistent with reactive hypertrophy. There was a progressive increase in the number of TUNEL-positive myocytes from 1 to 6 mo post-MI (2.9-fold increase at 6 mo; P < 0. 001 vs. sham). Thus LV remodeling late post-MI is associated with increased apoptosis in myocardium remote from the area of ischemic injury. The frequency of apoptosis is related to the severity of LV dysfunction.

Animals↗

Altered beta-adrenergic signal transduction in nonfailing hypertrophied myocytes from Dahl salt-sensitive rats.

Desensitization of the beta-adrenergic receptor (beta-AR) response is well documented in hypertrophied hearts. We investigated whether beta-AR desensitization is also present at the cellular level in hypertrophied myocardium, as well as the physiological role of inhibitory G (G(i)) proteins and the L-type Ca(2+) channel in mediating beta-AR desensitization. Left ventricular (LV) myocytes were isolated from hypertrophied hearts of hypertensive Dahl salt-sensitive (DS) rats and nonhypertrophied hearts of normotensive salt-resistant (DR) rats. Cells were paced at a rate of 300 beats/min at 37 degrees C, and myocyte contractility and intracellular Ca(2+) concentration ([Ca(2+)](i)) were simultaneously measured. In response to increasing concentrations of isoproterenol, DR myocytes displayed a dose-dependent augmentation of cell shortening and the [Ca(2+)](i) transient amplitude, whereas hypertrophied DS myocytes had a blunted response of both cell shortening and the [Ca(2+)](i) transient amplitude. Interestingly, inhibition of G(i) proteins did not restore beta-AR desensitization in DS myocytes. The responses to increases in extracellular Ca(2+) and an L-type Ca(2+) channel agonist were also similar in both DS and DR myocytes. Isoproterenol-stimulated adenylyl cyclase activity, however, was blunted in hypertrophied myocytes. We concluded that compensated ventricular hypertrophy results in a blunted contractile response to beta-AR stimulation, which is present at the cellular level and independent of alterations in inhibitory G proteins and the L-type Ca(2+) channel.

Adenylate Cyclase Toxin↗