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Biomedical subjects

A Anand

Publications and source records attributed to A Anand.

At least 73 records · Page 4Linked to original sources

Transient depressive relapse induced by catecholamine depletion: potential phenotypic vulnerability marker?

BACKGROUND: Although state-related alterations in catecholamine function have been well-described in depressed subjects, enduring abnormalities have been less reliably identified. In our study, medication-free subjects with fully remitted major depression underwent a paradigm of catecholamine depletion, via use of the tyrosine hydroxylase inhibitor alpha-methylparatyrosine. METHOD: Subjects underwent 2 sets of testing conditions in a double-blind, random-ordered, crossover design, approximately 1 week apart. They underwent active catecholamine depletion (via oral administration of 5 g alpha-methylparatyrosine) or sedation-controlled, sham catecholamine depletion (via oral administration of 250 mg diphenhydramine hydrochloride), during a 2-day observation. Serial mood ratings and blood samples were obtained. RESULTS: Fourteen subjects completed the active testing condition; 13 completed sham testing. Subjects experienced marked, transient increases in core depressive and anxiety symptoms, as demonstrated by a mean 21-point increase on Hamilton Depression Rating Scale scores. Furthermore, 10 (71%) of 14 subjects fulfilled relapse criteria during active testing, whereas 1 (8%) of 13 subjects did so during sham testing. The severity of the depressive reaction correlated with baseline plasma cortisol levels (r = 0.59; P =.04). CONCLUSIONS: Euthymic, medication-free subjects with a history of major depression demonstrate significant depressive symptoms when undergoing testing with alpha-methylparatyrosine. This depressive reaction may represent a reliable marker for a history of depression. Further work is needed to clarify the significance of this finding.

Adult↗

Cytomorphological features of salivary duct carcinoma ex pleomorphic adenoma: diagnosis by fine-needle aspiration biopsy with histologic correlation.

We report a case of salivary duct carcinoma arising from a pleomorphic adenoma (ex pleomorphic adenoma) in a parotid salivary gland of a 70-yr-old man. Fine-needle aspiration biopsy showed two distinct subsets of cells. There was the typical biphasic pattern of pleomorphic adenoma consisting of bland epithelial cells admixed with uniform spindle-shaped cells and chondromyxoid stroma. In addition, there were features of salivary duct carcinoma best demonstrated by necrosis and the presence of large polygonal cells arranged either singly or in rosettes, clusters or sheets reminiscent of ductal carcinoma of the breast. This case illustrates that the presence of background large polygonal cells and necrosis in an otherwise typical pleomorphic adenoma may suggest the diagnosis of a high-grade carcinoma, namely salivary duct carcinoma, which portends poor prognosis and requires aggressive treatment. Differential diagnosis from other carcinomas known to arise in pleomorphic adenoma is discussed.

Adenoma, Pleomorphic↗

Middle ear effusion: rate and risk factors in Australian children attending day care.

There have been no previous longitudinal studies of otitis media conducted in non-Aboriginal Australian children. This paper describes the rate and risk factors for middle ear effusion (MEE) in children attending day care in Darwin, Australia. A prospective cohort study of 252 children under 4 years was conducted in 9 day care centres over 12 fortnights between 24 March and 15 September 1997. Tympanometry was conducted fortnightly and multivariate analysis used to determine risk factors predicting MEE. The outcome of interest was the rate of type B tympanograms per child detected in either ear at fortnightly examinations. After adjusting for clustering by child, MEE was detected on average 4.4 times in 12 fortnights (37% of all examinations conducted). Risk factors associated with presence of effusion were younger age, a family history of ear infection, previous grommets (tympanostomy tubes), ethnicity and the day care centre attended. A history of wheeze appeared protective. These effects were modest (RR 0.57-1.70). Middle ear effusion is very common in children attending day care in Darwin. This has clinical importance, since MEE during early childhood may affect optimal hearing, learning and speech development. There is little scope for modification for many of the risk factors for MEE predicted by this model. Further study of the day care environment is warranted.

Child Day Care Centers↗

Limited efficacy of ketoconazole in treatment-refractory major depression.

The authors examined the efficacy of ketoconazole in 16 adults with treatment-refractory major depressive disorder. Subjects participated in a 6-week, double-blind, placebo-controlled trial. Assessments of mood were made using the Hamilton Rating Scale for Depression (HAM-D), the Beck Depression Inventory (BDI), and the Clinical Global Impression Scale (CGI). Results showed that none of eight patients randomly assigned to receive placebo and two of eight patients randomly assigned to receive ketoconazole met criteria for response. As a group, patients assigned to receive ketoconazole showed no significant reductions in HAM-D, BDI, or CGI scores during the 6-week trial compared with those receiving placebo. These findings suggest a limited efficacy for ketoconazole in patients with treatment-refractory major depression.

Adult↗

Drug-induced arterial pressure elevation is associated with arousal from NREM sleep in normal volunteers.

Abrupt changes in arterial pressure produce arousal in sleeping animals. To determine whether arterial pressure elevations can cause arousal from sleep in humans, we studied five healthy individuals without sleep complaints or cardiac abnormalities. Monitoring included electroencephalogram, electrooculogram, and electromyogram to determine stage sleep; finger cuff to measure arterial pressure; and electrocardiogram to measure heart rate. We administered intravenous bolus doses of either phenylephrine or saline after performing a dose-response curve to establish the amount of phenylephrine that produced a 20-mmHg increase in mean arterial pressure. Ten boluses of phenylephrine and ten boluses of saline were then administered in random order during stable non-rapid-eye-movement sleep. An observer blinded to the order of drug administration identified arousals using a standard definition. Arousals were five times more likely to occur after phenylephrine than after saline (58 vs. 12%; P = 0.0071). Phenylephrine administration produced heart rate slowing, indicative of baroreflex stimulation. We conclude that pharmacologically induced arterial pressure elevation is associated with arousal from sleep in normal volunteers.

Adrenergic alpha-Agonists↗

Genetic polymorphism in muscle biopsies of Duchenne and Becker muscular dystrophy patients.

Duchenne muscular dystrophy (DMD), with an incidence of one in 3500 male new borns, and its milder variant, Becker muscular dystrophy (BMD), are allelic X-linked recessive disorders, caused by mutations in the gene coding for dystrophin, a 427 kD cytoskeleton protein. There are no available molecular markers to differentiate these two. The purpose of this study was to study genetic polymorphism in muscular dystrophy and explore its potential in discriminating these two allelic forms of the disease. The results revealed unambiguously the presence of three transcripts : 598bp, 849bp and 1583bp long which are selectively expressed in the muscles afflicted with muscular dystrophy as compared to the normal muscle. 1583bp gene transcript was conspicuously present in the muscle tissues of both DMD and BMD patients whereas 598bp and 849bp long transcripts were exclusively present in DMD but not in BMD patients or normal human subjects. These gene transcripts had no sequence homology with dystrophin gene and these were also present in the families belonging to DMD and BMD patients. These results point to the fact that based upon the selective expression of these three gene transcripts, one could not only differentiate between DMD and BMD diseases at the molecular level, but also between normal and dystrophic muscle. Further, these findings also reveal that apart from dystrophin gene, these gene transcripts may also be responsible for the differential progression of DMD/BMD phenotype.

Biopsy↗

Progression of atypical ductal hyperplasia/carcinoma in situ of the pancreas to invasive adenocarcinoma.

Although atypical ductal hyperplasia and carcinoma in situ of the pancreas have been well-documented, the natural history and rate of progression of these lesions are unknown. We report two patients, 68 and 52 years of age, who underwent Whipple's procedures for chronic pancreatitis. Histologic sections of the pancreas from both patients showed numerous foci of atypical ductal hyperplasia/carcinoma in situ that extended to the surgical margins of resection. Twenty-nine years after the Whipple's procedure, the first patient had a fine needle aspiration biopsy of a mass in the residual pancreas. The fine needle aspirate and cell block showed a conventional infiltrating ductal carcinoma of the pancreas. Nine years after the Whipple's procedure, the second patient underwent a distal pancreatectomy for a mass involving the body and tail of the pancreas that histologically proved to be a conventional infiltrating ductal carcinoma. These two cases suggest that progression of atypical ductal hyperplasia/carcinoma in situ of the pancreas to invasive carcinoma may take many years. This information about the natural history of these lesions may provide impetus for early detection and improved therapy and survival. Specimens of chronic pancreatitis obtained by Whipple's procedure provide surgical pathologists with the opportunity to search and become familiar with atypical ductal lesions of the pancreas not associated with invasive carcinoma.

Adenocarcinoma↗

Histologic spectrum of arterial and arteriolar lesions in acute and chronic cocaine-induced mesenteric ischemia: report of three cases and literature review.

Gastrointestinal complications of cocaine abuse occur less frequently than those of the cardiovascular and nervous systems. The clinical history and pathologic findings of three patients with cocaine-induced mesenteric ischemia are described, and the mechanism of acute and chronic cocaine-induced mesenteric ischemia is discussed. The role of preoperative angiography in detecting occlusive arterial lesions so that arterial revascularization can be carried out is emphasized. Briefly, recent intravenous cocaine use in a 45-year-old man resulted in sharply demarcated small intestinal ischemia with perforation characterized by pseudomembranous enteritis. Histologic sections of the small-bowel resection showed intraluminal fibrin and intimal hyperplasia in rare submucosal arterioles. Two women, 29 and 35 years of age, both with a 2-year history of intravenous cocaine use, presented with acute abdominal pain and had angiographic documentation of occlusion of the celiac axis and the superior mesenteric arteries. Vascular bypasses were performed in both cases. Microscopic examination of both arteries and their branches revealed total obstruction by luminal thrombus with recanalization.

Adult↗

Primary renal angiosarcoma: a case report with immunohistochemical, ultrastructural, and cytogenetic features and review of the literature.

Primary angiosarcoma of the kidney is a rare tumor for which fewer than 10 case reports appear in the English literature. A case of primary renal angiosarcoma is reported, in which the tumor showed poorly differentiated spindled sarcoma admixed with typical angiomatous differentiation. Antibodies against CD31, CD34, Ulex europeus lectin type I, factor VIII-related antigen, cytokeratin (AE1/AE3), vimentin, S100 protein, epithelial membrane antigen, carcinoembryonic antigen, desmin, and smooth muscle actin were examined. CD31 showed strong diffuse membranous staining of cells in the well-differentiated areas and strong membranous staining in the spindled, poorly differentiated areas. CD34 showed strong cytoplasmic and membranous staining in both the poorly differentiated and well-differentiated areas. Staining for factor VIII-related antigen and Ulex europeus was less intense and was limited to the well-differentiated areas. Staining for cytokeratin (AE1-AE3), S100, carcinoembryonic antigen, epithelial membrane antigen, desmin, and smooth muscle actin were negative. Electron microscopy showed spindle cells containing abundant pinocytotic vesicles, vimentin-type intermediate filaments, and rare Weibel-Palade bodies. A complex karyotype was found. Our findings suggest that CD31 and CD34 are useful in defining endothelial differentiation in poorly differentiated angiosarcomas in which reactions for Ulex europeus lectin type I and factor VIII-related antigen may be equivocal.

Aged↗

Expression of inducible nitric oxide synthase by macrophages in rat lung.

Nitric oxide (NO) is a short-lived free radical that is secreted by pulmonary macrophages (Mø). An inducible isoform of NO synthase (iNOS) catalyses the production of NO and is activated by lipopolysaccharide and certain T-helper(h) 1 cytokines, including interferon-gamma and TNF-alpha. In the present study, iNOS+ interstitial cells were demonstrated in the alveolar wall of normal Lewis rat lung. Enzymatic digests of normal lung showed that approximately one third of pulmonary ED1+ interstitial Mø (IM) were iNOS+ and secreted modest amounts of NO without ex vivo stimulation, whereas normal alveolar macrophages (AM) were iNOS- and showed no basal NO secretion. When incubated with heat-killed Listeria monocytogenes (HKL) in vitro, AM secreted larger amounts of NO than did IM. Recombinant murine GM-CSF stimulated production of NO by AM but not by IM. However, when IM were costimulated with GM-CSF and IFN-gamma, they expressed a marked increase in NO production. Intratracheal challenge with HKL yielded decreased NO production by IM. We conclude that iNOS+ IM are present in normal rat lung, where they regulate the pulmonary cell-mediated immune response to antigen.

Animals↗

Effect of pindolol in hastening response to fluoxetine in the treatment of major depression: a double-blind, placebo-controlled trial.

OBJECTIVE: In two preliminary studies, pindolol produced robust results in hastening clinical response to antidepressant drugs in depressed patients. Validity of those pilot studies was limited by use of an open-label, unblinded study design, and so the authors conducted a double-blind, placebo-controlled trial to assess the effectiveness of pindolol in hastening response to fluoxetine. METHOD: Drug-free outpatients with major depression were concurrently treated with fluoxetine (20 mg/day) and either placebo or pindolol (5.0 mg b.i.d. or 2.5 mg t.i.d.), for 6 weeks, in a randomized, double-blind manner. After 6 weeks, all patients received fluoxetine and placebo and were followed for 3 further weeks in a single-blind manner. RESULTS: Forty-three patients completed at least 1 week of the protocol. Rates of partial remission after 2 weeks of treatment with fluoxetine and either pindolol or placebo were 17% (four of 23 patients) and 20% (four of 20 patients), respectively. At study completion, 65% of the patients (N = 28) demonstrated at least a partial remission, and there was no difference between treatment groups. The pindolol group, but not the placebo group, demonstrated significant reductions in blood pressure and pulse rate. The average time to remission and the rates of attrition, overall response, and side effects were similar in the two groups. CONCLUSIONS: These findings do not support the efficacy of pindolol in hastening clinical response in patients treated with fluoxetine.

Adolescent↗

Addition of desipramine to serotonin reuptake inhibitors in treatment-resistant obsessive-compulsive disorder.

OBJECTIVE: The purpose of this study was to determine whether combined treatment with a selective serotonin reuptake inhibitor (SSRI) and a norepinephrine reuptake inhibitor, desipramine, effectively reduces obsessive-compulsive symptoms in patients who do not respond to SSRIs. METHOD: In a double-blind study, desipramine or placebo was added for 6 or 10 weeks to the treatment of 30 patients with obsessive-compulsive disorder whose symptoms were refractory to SSRI treatment (fluvoxamine, fluoxetine, or sertraline) alone. RESULTS: There were no significant differences between the adjunctive desipramine and placebo groups in obsessive-compulsive or depressive symptoms. CONCLUSIONS: These data suggest that clomipramine's possibly superior efficacy in the treatment of obsessive-compulsive symptoms may not stem from its capacity to inhibit reuptake of norepinephrine.

1-Naphthylamine↗

Control of male sexual behavior and sexual orientation in Drosophila by the fruitless gene.

Sexual orientation and courtship behavior in Drosophila are regulated by fruitless (fru), the first gene in a branch of the sex-determination hierarchy functioning specifically in the central nervous system (CNS). The phenotypes of new fru mutants encompass nearly all aspects of male sexual behavior. Alternative splicing of fru transcripts produces sex-specific proteins belonging to the BTB-ZF family of transcriptional regulators. The sex-specific fru products are produced in only about 500 of the 10(5) neurons that comprise the CNS. The properties of neurons expressing these fru products suggest that fru specifies the fates or activities of neurons that carry out higher order control functions to elicit and coordinate the activities comprising male courtship behavior.

Age Factors↗

Reflex stimulation of aortic chemoreceptors through the stellate ganglion during hypoxia and hypotension in cats.

1. In cats anaesthetized with sodium pentobarbitone (35 mg kg-1), an investigation was made of the mechanisms underlying the enhancement of aortic chemoreceptor activity through the excitatory effect mediated by the sympathetic outflow to them during hypoxia and hypotension. 2. Removal of the right stellate ganglion significantly (P < 0.01) reduced the responses of the chemoreceptors to hypoxia and hypotension. Injection of a bolus of sodium pentobarbitone reduced the responses before, but not after, stellectomy. This indicated that the excitatory sympathetic influence on the chemoreceptors (attributed to glomeral vasoconstriction leading to reduction in blood flow) is exerted entirely through the right stellate ganglion. This excitatory effect was abolished after cutting the vagi and both carotid sinus nerves. 3. It is concluded that, in addition to the direct excitatory effect of hypoxia on aortic chemoreceptors, a reflex chemoreceptor excitatory component is mediated through the vagi, carotid sinus nerves and right stellate ganglion.

Animals↗