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Biomedical subjects

A Singh

Publications and source records attributed to A Singh.

At least 181 records · Page 10Linked to original sources

Familial carnitine transporter defect: A treatable cause of cardiomyopathy in children.

Carnitine transporter defect is characterized by severely reduced transport of carnitine into skeletal muscle, fibroblasts, and renal tubules. All children with dilated cardiomyopathy or hypoglycemia and coma should be evaluated for this transporter defect because it is readily amenable to therapy that results in prolonged prevention of cardiac failure. This article details the cases of 3 children who have carnitine transporter defect, 2 of whom had severe dilated cardiomyopathy. Plasma and skeletal muscle carnitine levels were extremely low and both children were treated with oral L-carnitine, resulting in resolution of severe cardiomyopathy and prevention of recurrence or cardiac enlargement for more than 5 years. The third child had hypoglycemia and coma as presenting findings of the transporter defect and had mild left ventricular hypertrophy but no cardiac failure. The prognosis for long-term survival in pediatric dilated cardiomyopathy is poor. Children with carnitine transporter defect can have a different outcome if their underlying condition is detected early and treated medically.

Biological Transport↗

The legendary superior strength of the Pfannenstiel incision: a myth?

OBJECTIVE: This study was undertaken to determine whether there is a difference in the frequency of fascial dehiscence between midline vertical lower abdominal and Pfannenstiel incisions among women undergoing obstetric and gynecologic operations. STUDY DESIGN: A case-control study of 48 cases of fascial dehiscence complicating 17, 995 major operations (8950 cesarean deliveries and 9405 gynecologic procedures) during a 6-year period at Wayne State University Hutzel Hospital, Detroit, was performed. Univariate analysis identified significant independent variables related to fascial dehiscence. Stepwise logistic regression analysis then identified those risk factors that were independently associated with fascial dehiscence. RESULTS: Among the 48 patients who underwent repair of fascial dehiscence after a major obstetric or gynecologic operation, 27 were from the obstetric service and 21 were from the benign and cancer gynecologic services. Wound dehiscence occurred in 10 vertical incisions and 17 Pfannenstiel incisions among the obstetric patients and in 12 vertical and 9 Pfannenstiel incisions among the gynecologic patients. The risk for dehiscence with vertical lower abdominal incisions was not increased with respect to that associated with Pfannenstiel incisions (P =.39, 2-tailed). This finding was true for all patients (odds ratio, 1.3; 95% confidence interval, 0.7-2.6), obstetric patients (odds ratio, 1.3; 95% confidence interval, 0.5-3.4), and gynecologic patients (odds ratio, 1.5; 95% confidence interval, 0.5-4.0). Forty-seven of the 48 case patients had documented wound infections, compared with 1 of the 144 control subjects (P <.0001, odds ratio, 37.8; 95% confidence interval, 14.8-96.8). CONCLUSION: Wound infection was the most important risk factor for fascial dehiscence among women who underwent major obstetric and gynecologic operations. Our results do not support the long-held belief that Pfannenstiel incisions are stronger than lower abdominal vertical incisions and reduce the risk for fascial dehiscence.

Abdomen↗

Studies of ion-exchange resin complex of chloroquine phosphate.

High-potency adsorbates of chloroquine phosphate (CQP) were prepared by the batch method using a polyacrylic acid ion-exchange resin. Taste evaluation of the adsorbates shows significant masking of the bitterness of the drug. The complex formation was complete at pH 6.0. Stability studies at 37 degrees C, 45 degrees C, and 60 degrees C indicated that the complex was stable at all conditions for 1 month. In vitro release studies revealed complete drug elution from the complex at pH 1.2 and 2.0.

Acrylic Resins↗

Potential applications of carbomer in oral mucoadhesive controlled drug delivery system: a review.

Carbomers are extensively being used in controlled drug delivery systems (CDDS). They are also finding numerous applications in oral mucoadhesive drug delivery because of their ability to interact with the mucus glycoprotein and to remain localized to a specific site. The present review aims at giving an insight into the potential application of carbomers in mucoadhesive CDDS. This review deals with the physicochemical properties of carbomers and various mechanisms of mucoadhesion. The mechanism for the release of the drug, both water soluble and water insoluble, is discussed. The use of carbomers in oral delivery of peptides or protein-based drugs is also covered.

Acrylic Resins↗

Cocaine-induced reflex sympathetic dystrophy.

Reflex sympathetic dystrophy (RSD) usually follows traumatic injuries or neurologic disorders. The authors report a rare case of RSD that followed intraarterial administration of cocaine in a patient with a history of intravenous drug abuse. The cocaine was self-administered inadvertently into the femoral artery rather than the femoral vein. Despite the intense pain, swelling, and dermatologic changes that followed, the diagnosis of RSD was not considered until scintigraphic studies suggested it. A combination of normal radiographs, a normal leukocyte study, and an abnormal bone scan in the region of tenderness and swelling excluded other possibilities and suggested RSD. In our patient, RSD was likely caused by an ischemic autonomic injury from the vasoconstrictor action of cocaine. Clinical follow-up and relief using phentolamine, an alpha-adrenergic blocker and vasodilator, made the diagnosis of RSD most likely.

Cocaine-Related Disorders↗

Biotransformation of hydroxylaminobenzene and aminophenol by Pseudomonas putida 2NP8 cells grown in the presence of 3-nitrophenol.

Biotransformation products of hydroxylaminobenzene and aminophenol produced by 3-nitrophenol-grown cells of Pseudomonas putida 2NP8, a strain grown on 2- and 3-nitrophenol, were characterized. Ammonia, 2-aminophenol, 4-aminophenol, 4-benzoquinone, N-acetyl-4-aminophenol, N-acetyl-2-aminophenol, 2-aminophenoxazine-3-one, 4-hydroquinone, and catechol were produced from hydroxylaminobenzene. Ammonia, N-acetyl-2-aminophenol, and 2-aminophenoxazine-3-one were produced from 2-aminophenol. All of these metabolites were also found in the nitrobenzene transformation medium, and this demonstrated that they were metabolites of nitrobenzene transformation via hydroxylaminobenzene. Production of 2-aminophenoxazine-3-one indicated that oxidation of 2-aminophenol via imine occurred. Rapid release of ammonia from 2-aminophenol transformation indicated that hydrolysis of the imine intermediate was the dominant reaction. The low level of 2-aminophenoxazine-3-one indicated that formation of this compound was probably due to a spontaneous reaction accompanying oxidation of 2-aminophenol via imine. 4-Hydroquinone and catechol were reduction products of 2- and 4-benzoquinones. Based on these transformation products, we propose a new ammonia release pathway via oxidation of aminophenol to benzoquinone monoimine and subsequent hydrolysis for transformation of nitroaromatic compounds by 3-nitrophenol-grown cells of P. putida 2NP8. We propose a parallel mechanism for 3-nitrophenol degradation in P. putida 2NP8, in which all of the possible intermediates are postulated.

Aminophenols↗

Heterogeneous spectrum of coreceptor usage among variants within a dualtropic human immunodeficiency virus type 1 primary-isolate quasispecies.

Human immunodeficiency virus type 1 (HIV-1) variants that use the coreceptor CCR5 for entry (R5; macrophage tropic) predominate in early infection, while variants that use CXCR4 emerge during disease progression. Some late-stage variants use CXCR4 alone (X4; T-cell tropic), while others use both CXCR4 and CCR5 (R5X4; dualtropic). It has been proposed that dualtropic R5X4 strains are intermediates in the evolution from R5 to X4, and we hypothesized that a dualtropic primary-isolate quasispecies might contain variants that represent the spectrum of coreceptor use in vivo. We generated a panel of 35 functional full-length env clones from the primary-isolate quasispecies of a dualtropic prototype strain, HIV-1 89.6(PI). Thirty of the functional env clones (86%) were R5X4, four (11%) were R5, and one (3%) was predominantly X4. V3 to V5 sequences did not reveal clustering by coreceptor usage, and no specific sequence motif or V3 charge pattern corresponded to coreceptor utilization. Complete sequencing of seven functionally divergent Env proteins revealed > or =98.7% homology and conservation of structurally important domains. Chimeras between the R5X4 89.6 prototype and an R5 variant indicated that multiple regions contributed to the use of CXCR4, while chimeras with the X4 variant implicated a single residue in V4 in CCR5 use. These results confirm, at the molecular level, both that dualtropic variants are a predominant component of late-stage syncytium-inducing isolates and that variants restricted to each coreceptor coexist with dualtropic species in vivo. Coreceptor-restricted minority variants may reflect residual R5 species from earlier in disease as well as emerging X4 variants.

Amino Acid Sequence↗

Genetic variation and relationship among and within Withania species as revealed by AFLP markers.

Withania somnifera is an important medicinal plant, and its anticancerous properties have been attributed to various classes of withanolide compounds. The objective of the present study was to investigate the inter- and intraspecific genetic variation present in 35 individuals of W. somnifera and 5 individuals of W. coagulans using AFLP (amplified fragment length polymorphism) marker technique. The information about genetic variation determined from AFLP data for 40 individuals was employed to estimate similarity matrix value based on Jaccard's coefficient. The similarity values were further used to construct a phenetic dendrogram revealing the genetic relationships. The dendrogram generated by UPGMA (unweighted pair group method of arithmetic averages) distinguished W. somnifera from W. coagulans and formed two major clusters. These two main clusters shared a similarity coefficient of 0.3, correlating with the high level of polymorphism detected. The dendrogram further separated W. somnifera into three subclasses corresponding to Kashmiri and Nagori groups and an intermediate type. The AFLP profile of Kashmiri individuals was distinct from that of the Nagori group of plants. The intermediate genotype was distinct as it shared bands with both the Kashmiri and Nagori individuals, even though it was identified as a Kashmiri morphotype. Furthermore, the intermediate type shared a similarity coefficient of 0.8 with the Kashmiri individuals. The present work revealed low levels of variation within a population though high levels of polymorphism were detected between Nagori and Kashmiri populations. The ability of AFLP markers for efficient and rapid detection of genetic variations at the species as well as intraspecific level qualifies it as an efficient tool for estimating genetic similarity in plant species and effective management of genetic resources.

DNA, Plant↗

Cyclooxygenase-2-derived prostaglandin D(2) is an early anti-inflammatory signal in experimental colitis.

The ability of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors to exacerbate inflammatory bowel disease suggests that prostaglandins are important anti-inflammatory mediators in this context. Prostaglandin D(2) has been suggested to exert anti-inflammatory effects. We investigated the possibility that prostaglandin D(2) derived from cyclooxygenase-2 plays an important role in downregulating colonic inflammation in rats. Colitis was induced by intracolonic administration of trinitrobenzene sulfonic acid. At various times thereafter (from 1 h to 7 days), colonic prostaglandin synthesis and myeloperoxidase activity (index of granulocyte infiltration) were measured. Prostaglandin D(2) synthesis was elevated >4-fold above controls within 1-3 h of induction of colitis, preceding significant granulocyte infiltration. Treatment with a selective cyclooxygenase-2 inhibitor abolished the increase in prostaglandin D(2) synthesis and caused a doubling of granulocyte infiltration. Colonic granulocyte infiltration was significantly reduced by administration of prostaglandin D(2) or a DP receptor agonist (BW-245C). These results demonstrate that induction of colitis results in a rapid increase in prostaglandin D(2) synthesis via cyclooxygenase-2. Prostaglandin D(2) downregulates granulocyte infiltration into the colonic mucosa, probably through the DP receptor.

Animals↗

Differences in the meiotic pairing behavior of gonosomal heterochromatin between female and male Microtus agrestis: implications for the mechanism of heterochromatin amplification on the X and Y.

It is generally thought that pairing and recombination between the X and Y chromosome in eutherian mammals is important for the occurrence of normal meiotic division and the production of functional gametes. Microtus agrestis is one of the examples whose giant and heterochromatin-rich sex chromosomes fail to establish a durable association at any stage of the first meiotic division in males. In contrast, in females, synapsis starts in the euchromatic short arm and pairing progresses unidirectionally and continues until both X chromosomes have paired completely, as can be demonstrated by the use of fluorescence in situ hybridization with a sequence confined to the non-centromeric, gonosomal heterochromatin. However, compared with euchromatin, this association is apparently ephemeral and breaks off precociously in the pachytene and metaphase I stages. We demonstrate that a middle repetitive element is localized interspersed in the noncentromeric heterochromatin of both X and Y, except the telomeric region of the Y. No differences could be detected at the molecular level between male and female DNA, indicating that at least the bulk of these elements are organized in the same manner on the X and Y. Our data imply that the loss of synapsis and recombination between the X and Y might have preceded the process of heterochromatin amplification in the course of Microtinae evolution. Since asynapsed elements are particularly susceptible to DNA strand breaks during prophase I, DNA repair of double-strand breaks involving heterochromatic segments of the X and Y could have resulted in translocations of larger segments from the X to the Y or vice versa during the course of chromosome evolution of the gonosomes, explaining the homology at the molecular level between the heterochromatin of the asynaptic X and Y in M. agrestis.

Animals↗

Functional and neuroanatomic correlations in poststroke depression: the Sunnybrook Stroke Study.

BACKGROUND AND PURPOSE: The purpose of our study was to determine the functional and neuroanatomic correlates of poststroke depressive symptoms. METHODS: Patients with consecutive admissions to a regional stroke center for new-onset unilateral hemispheric stroke who met World Health Organization and National Institute of Neurological and Communicative Disorders and Stroke criteria were eligible for inclusion in a longitudinal study. Acutely, patients underwent CT scanning, and at 3 months and 1 year after stroke, depressive symptoms were assessed by using both the Montgomery-Asberg Depression Rating Scale and the Zung Self-Rating Depression Scale. The Functional Independence Measure (FIM) served as an indication of functional outcome and was obtained at 1 month, 3 months, and 1 year after stroke, along with other demographic information. The Talairach and Tournoux stereotactic atlas was used for the primary determination of CT lesion localization. Lesion proximity to the anterior frontal pole was also measured. RESULTS: Eighty-one patients participated in the longitudinal study. Stepwise linear regression analyses generated a highly significant model (F(3,76)=9.8, R(2)=28%, P<0.0005), with lower 1-month total FIM scores, living at home, and damage to the inferior frontal region predicting higher depression scores at 3 months. Similarly, lower 3-month total FIM scores correlated with higher 3-month depression scores, and lower 1-year total FIM scores correlated with higher 1-year depression scores. CONCLUSIONS: Functional measures correlated with poststroke depression across time and, together with neuroanatomic measures, predicted depressive symptoms longitudinally. Although inferior frontal lesion location, irrespective of side, appeared to play a role as a risk factor in this study, the degree of functional dependence after stroke imparted the greatest risk.

Activities of Daily Living↗

Endocrine response to high-intensity exercise: dose-dependent effects of dexamethasone.

We recently reported that in 30-50% of healthy men and women the release of ACTH and cortisol stimulated by exercise is not suppressed by prior administration of a 4-mg dose of dexamethasone (DEX). We now explore other potential differences between these subjects and those whose exercise response was suppressed by examining the effect of a smaller, 1-mg, dose of DEX on exercise-stimulated ACTH and cortisol. Men (n = 15) and women (n = 9) were studied during three high intensity exercise tests: one after taking placebo, one after taking 1 mg DEX, and one after taking 4 mg DEX. Before participation, subjects underwent a test for classification as either a high (HR; n = 10) or low (LR; n = 14) reactor and a maximal exercise test to assess maximal aerobic capacity. Distinct dose-related reductions in plasma concentrations of ACTH, cortisol, and dehydroepiandrosterone (DHEA) were noted for HR under the treatment conditions, whereas both doses of DEX blocked ACTH, cortisol, and DHEA release in LR. Furthermore, basal plasma cortisol, DHEA, and DHEA sulfate were significantly higher in HR compared to LR. Thus, there are inherent basal and stress-reactive differences in HR and LR, and these differences may be useful in constructing a model for the mechanisms and physiological regulation of hypothalamic-pituitary-adrenal axis activation. The question of whether these differences in reactivity of the ACTH-cortisol axis between the HR and LR groups have implications for individual short term function or long term health remains to be answered.

Adrenocorticotropic Hormone↗

Nimesulide: some pharmaceutical and pharmacological aspects--an update.

Nimesulide, a non-steroidal anti-inflammatory drug (NSAID), is administered orally or rectally twice daily for a variety of inflammation and pain states. This is a unique NSAID, not only because of its chemical structure but also because of its specific affinity to inhibit cyclooxygenase-2 (COX-2), thus exerting milder effects on the gastrointestinal mucosa. Current data on selective COX-2 inhibitors suggest that they may have an efficacy similar to that of standard NSAIDs. Initial general clinical experience with selective COX-2 inhibitors appears to show that they are particularly promising in individuals at risk because of renal diseases, hypertension or congestive heart failure. Various experimental models and clinical studies have demonstrated the anti-inflammatory efficacy of nimesulide. Nimesulide is superior, or at least comparable in efficacy, to other NSAIDs, but is better tolerated and has less potential for adverse reactions. Thus, selective COX-2 inhibitors should have anti-inflammatory effects devoid of side effects on the kidney and stomach. They may also demonstrate new important therapeutic benefits as anticancer agents as well as help prevention of premature labour and even retard the progression of Alzheimer's disease. No clinically significant drug interactions have been reported for nimesulide. Not much has been reported about the pharmaceutical aspects of nimesulide. Its poor aqueous solubility poses bioavailability problems in-vivo. This could be overcome by the formation of inclusion complexes with beta-cyclodextrin, as has been reported by various researchers. However, absence of any in-vivo data regarding the relative absorption of nimesulide from beta-cyclodextrin complex compared with that from conventional formulations of the drug makes the use of such fast-releasing complexes rather questionable. Only a limited number of assay procedures (HPLC, spectrophotometric, spectrofluorimetric) for the determination of nimesulide and its metabolite in plasma/urine samples or in dosage forms have been reported in the literature. The purpose of this review is to provide a concise overview of the pharmacological and pharmaceutical profile of nimesulide. Various investigations carried out recently are reported, although older references to research performed on nimesulide have also been included, where appropriate.

Animals↗

Proliferative myositis arising in the tongue.

We describe a rare case of proliferative myositis affecting the lateral border of the tongue. The site of the lesion and its gross pathological presentation were highly suggestive of a malignant process. Subsequent biopsy and characteristic histological appearance led to the diagnosis of this benign condition. This is the first reported case of a painful presentation of proliferative myositis involving the tongue. This report serves to remind the head and neck surgeon of the need to obtain histological diagnosis of malignancy before embarking upon radical surgical treatment. We recommend careful follow-up to ensure complete resolution of the lesion.

Biopsy↗

Cyclooxygenase isoenzymes and newer therapeutic potential for selective COX-2 inhibitors.

Cyclooxygenase (COX), also known as prostaglandin G/H synthase, is a membrane-bound enzyme responsible for the oxidation of arachidonic acid to prostaglandins that was first identified over 20 years ago. In the past decade, however, more progress has been made in understanding the role of cyclooxygenase enzymes in various pathophysiological conditions. Two cyclooxygenase isoforms have been identified and are referred to as COX-1 and COX-2. COX-1 enzyme is constitutively expressed and regulates a number of housekeeping functions such as vascular hemostasis and gastroprotection, whereas COX-2 is inducible (i.e., sites of inflammation) by number of mediators such as growth factors, cytokines and endotoxins. Nonsteroidal antiinflammatory drugs (NSAIDs) produce their therapeutic effects through inhibition of COX, the enzyme that makes prostaglandins. Nonselective inhibition of COX isoenzyme leads to not only beneficial therapeutic effects but also a number of detrimental effects. Beneficial effects are due to inhibition of COX-2 and detrimental effects are due to inhibition of physiological COX-1. The present review discusses the biology as well as the role of these COX isoenzymes in various pathophysiological conditions.

Animals↗

[Ovarian mucinous adenocarcinoma, mucocele of the appendix and pseudomyxoma peritonei: case report with immunohistochemical analysis].

Women with pseudomyxoma peritonei may have both, appendiceal and ovarian mucinous tumors, and there is a considerable debate regarding the site of origin of the tumor in such cases. Recent studies which have investigated the histological and immunohistochemical profile of these tumors showed, that ovarian tumors in most cases are secondary to the appendiceal tumors. In our case report we demonstrate that, despite of extensive immunohistochemical examinations (analysis of CK 7, 18, 20, CEA, HAM 56), it may be difficult to determine the histogenetic origin of pseudomyxoma peritonei.

Adenocarcinoma, Mucinous↗