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Biomedical subjects

A Mishra

Publications and source records attributed to A Mishra.

At least 19 recordsLinked to original sources

Peyer's patch eosinophils: identification, characterization, and regulation by mucosal allergen exposure, interleukin-5, and eotaxin.

The gastrointestinal immune system is traditionally thought to be composed of lymphocytes located within Peyer's patches and the lamina propria. We have recently reported that eosinophils also reside in the gastrointestinal tract during healthy states, in particular, within the lamina propria, and that these cells substantially increase after oral allergen exposure. We now demonstrate the presence of eosinophils in Peyer's patches and characterize the signals that regulate the accumulation of eosinophils in Peyer's patches. In contrast to the lamina propria, intestinal Peyer's patches have very low levels of eosinophils under healthy states. However, elevated levels of interleukin-5 (IL-5), generated by transgenic or pharmacologic approaches, result in a dramatic increase in eosinophil levels in Peyer's patches. Most eosinophils are located in the outer cortex and interfollicular regions of the Peyer's patches. To dissect the mechanism of eosinophil trafficking to Peyer's patches, the role of eotaxin was examined. Mice transgenic for IL-5 and genetically deficient in eotaxin were found to have reduced levels of eosinophils in Peyer's patches compared with IL-5-transgenic mice. To prove that eosinophils also traffic to Peyer's patches in wild-type mice, allergic hypersensitivity was induced and Peyer's patches were examined. Exposure to mucosal allergen promoted marked accumulation of eosinophils in Peyer's patches and this process was attenuated in eotaxin-deficient mice. In summary, these data demonstrate that elevated levels of IL-5 and mucosal allergen exposure promote eotaxin-dependent eosinophil trafficking to Peyer's patches. These studies suggest that eosinophils may cooperate with lymphocytes in the development of mucosal immune responses in the gastrointestinal tract. (Blood. 2000;96:1538-1544)

Animals↗

A critical role for eotaxin in experimental oral antigen-induced eosinophilic gastrointestinal allergy.

Despite marked advances in the understanding of allergic responses, the mechanisms regulating gastrointestinal allergy are not very well understood. We have developed a model of antigen-induced eosinophil-associated gastrointestinal allergy and characterized the role of eotaxin and IL-5. Challenge of allergen-sensitized mice with oral allergen, in the form of enteric-coated beads, resulted in marked allergen-specific IgG(1) and IgE, Th(2)-type (IL-4 and IL-5) cytokine production, and eosinophil accumulation in the blood and small intestine. In the genetic absence of eotaxin, a chemokine constitutively expressed in the gastrointestinal tract, eosinophil recruitment into the small intestine was ablated, and these mice developed enhanced eosinophil accumulation in the blood compared with wild-type mice. Interestingly, in the absence of IL-5, allergen challenge promoted partial eosinophil accumulation into the small intestine and a decline in circulating eosinophil levels. Collectively, these results establish that the accumulation of gastrointestinal eosinophils is antigen induced, can occur independent of IL-5, and provides a molecular mechanism to explain the dichotomy between peripheral blood and tissue eosinophilia. Furthermore, eotaxin is identified as a critical regulator of antigen-induced eosinophilic inflammation in the gastrointestinal tract.

Anaphylaxis↗

Aural foreign bodies.

At KGMC Lucknow, 168 pediatric cases with aural foreign bodies (FB) were reviewed. Most of the FB were self-inflicted and seen in children under 5 years of age (69.64%), within 24 hours (91.66%) of impaction. 86.30% of FB were seen to impact in external auditory canal (EAC) and their nature revealed predominance of nonvegetative inanimate FBs (43.45%). The TM perforation was encountered in only 6.54% of cases. If the FB is a living insect, it should be drowned before being manipulated. Syringing is the method of choice for a nonimpacted relatively small FB, even if it is vegetative. It is to be avoided in the 'potential' cases of external otitis or in cases with severely impacted wax. For a tightly wedged smooth rounded FB the hook and forceps are preferred in superficially and deep lying FBs respectively. A dissociate anaesthesia (ketamine) appears to be a better choice than general anaesthesia. An end-aural incision should be preferred over post-aural one and canalplasty for access of FB should be carried out wherever necessary. The presence of otorrhoea in cases of penetrating FB or aural myasis should be dealt on the lines of otitis media after removing the FB concerned.

Adolescent↗

Aerodigestive foreign bodies.

Accidents with foreign bodies (FBs) are most common within the first two years of life. The airway FBs present a diagnostic dilemma as both the history and the investigations can be misleading. The persistent hypoxia presents a threat to life as does extraction. Moreover, the chemical pneumonitis induced by vegetative FB makes the situation even more worse. The FB of digestive tract are comparatively benign unless long standing. It is neither necessary for the airway FB to present with respiratory symptoms and signs nor for the FB of digestive tract to complain of dysphagia/throat pain. Oesophagoscopy may have to be done if an esophageal FB is causing only recurrent respiratory infections without dysphagia. The situation in dealing with FB varies from site to site in the aerodigestive tract. This article stresses the various dubious factors including the history, examination and investigation which can lead to misdiagnosis and also those problems which are encountered during planned extraction as well as post-operatively.

Airway Obstruction↗

Surgical strategies in patients at high risk for stroke undergoing coronary artery bypass grafting.

BACKGROUND: Perioperative stroke represents one of the major complications following coronary artery bypass grafting (CABG). The present study was designed to evaluate the use of an individualized surgical approach for reducing neurological injury in patients undergoing CABG at high risk of stroke from aortic atherosclerosis or carotid disease. METHODS: Between January 1993 and June 1999, 6,138 patients undergoing elective CABG were evaluated by intraoperative transesophageal echocardiography. Patients were screened preoperatively for internal carotid artery disease. Based on the intraoperative transesophageal echocardiography findings the surgical technique was individualized: hypothermic circulatory arrest with aortic atherectomy, CABG combined with transmyocardial laser revascularization on the beating heart, off-pump CABG by midsternotomy, ministernotomy, minimally invasive direct CABG, hybrid procedure, and so on. Patients were divided into four groups: a low-risk group (no significant aortic or carotid disease); an aortic atheromatous disease group (A.ATH); a carotid disease group (CD); and a carotid disease combined with aortic atheromatous disease group (CD + A.ATH). RESULTS: The incidence of stroke in the low-risk group (n = 5,043) was 0.92% compared with 0.96% in the A.ATH group (n = 918). In the CD group (n = 166) the incidence of stroke was 0.6% whereas it was 0% in the CD + A.ATH group (n = 11). CONCLUSIONS: Preoperative and intraoperative screening can detect extensive atherosclerosis of the proximal aorta and internal carotid artery. Selective use of surgical techniques in this group of high-risk patients can prevent adverse neurologic sequelae while achieving complete myocardial revascularization.

Aged↗

Quality of life in patients with spinal cord injury receiving Viagra (sildenafil citrate) for the treatment of erectile dysfunction.

STUDY DESIGN: A multicenter, randomized, double-blind, placebo-controlled, flexible-dose, two-way crossover study conducted June 1996 through January 1997. OBJECTIVES: To evaluate the effect of sildenafil citrate (VIAGRA(R)) on the quality of life (QoL) of men with erectile dysfunction (ED) caused by spinal cord injury (SCI). SETTING: Study centers in Australia, Belgium, France, Germany, Norway, Sweden and the United Kingdom. METHODS: Questions 13 and 14 of the 15-item International Index of Erectile Function (IIEF) addressed QoL issues directly related to ED in 178 men with SCI. A 5-item questionnaire addressing concerns that men had about their erection problems was also used to evaluate the impact of ED on QoL. Several commonly used psychometric instruments, including the Medical Outcomes Survey (MOS) Short Form-12, Psychological General Well-Being Index, and MOS Family Survey, assessed general QoL issues. RESULTS: Significant improvements were seen for overall satisfaction with sex life (IIEF Q13), sexual relationship with partner (IIEF Q14), and concerns about erectile problems (P<0.0001). Improvements were reported in scores for the generic QoL parameters of mental health, well-being, depression, and anxiety (P<0.05 sildenafil versus placebo). CONCLUSION: Treatment with sildenafil can significantly improve key QoL parameters in men with ED caused by SCI. SPONSORSHIP: This study was funded by Pfizer Inc. Spinal Cord (2000) 38, 363 - 370.

Adult↗

Extradural meningioma en-plaque of the cervical cord.

A rare case of cervical extradural en-plaque meningothelial meningioma is reported. The magnetic resonance imaging revealed an extradural sheet of tumor encasing the cervical cord from anterior, posterior and right lateral aspects and emerging from the right C3-4 intervertebral foramina. Though a differential diagnosis of lymphoma and tubercular granulation tissue were considered, its isointense intensity patterns on T1 and T2 weighted images and the intratumoral calcification on intrathecal contrast computed tomographic scan suggested a meningioma. At surgery, the lesion was fibrous, avascular and densely adherent to the dura. The radiological features and management options of the lesion are discussed.

Adult↗

Bleomycin-mediated pulmonary toxicity: evidence for a p53-mediated response.

Bleomycin damages DNA and causes lung injury and fibrosis. To determine whether bleomycin is associated with the appearance of DNA damage-inducible proteins, C3H mice received either 0.4 mg bleomycin or normal saline intratracheally and were killed 1 to 14 d later. The lungs were examined for expression of p53, p21(WAF1/PiCl), and proliferating cell nuclear antigen (PCNA) using immunohistochemistry and Western blotting. p53-positive cells first appeared at 5 d after treatment and peaked at 7 d; PCNA-positive cells appeared at 1 d after treatment and peaked at 7 d; and p21-positive cells appeared at 5 d and peaked at 9 d. Western blot analysis confirmed that bleomycin upregulated the DNA damage-inducible proteins in a similar fashion. This is the first evidence that bleomycin causes a p53-dependent response associated with acute injury in the lung.

Animals↗

Oropharyngeal foreign body.

An unusual extremely benign course of an 8 cm long, rusting, metallic oropharyngeal foreign body that had entered post-aurally (penetration injury) four years previously to lie completely within the pharyngeal lumen has not yet been reported in the world literature. The need for additional investigations and special precautions to be taken during surgical extraction are highlighted.

Accidents↗

Glutathione reduces the toxicity associated with antitumor therapy of ascites fluid adsorbed over Staphylococcus aureus Cowan I in tumor bearing mice.

It has been well documented in the literature that the removal of circulatory immune complexes (CICs) from the host circulation leads to the immunopotentiation as well as generation of antitumor responses in a variety of tumors in rats, cats, dogs and human patients. CICs are the major immunosuppressive factors in tumor bearing host. Protein A (PA) has been extensively used for the removal of these CICs from the sera/plasma of tumor bearers, because PA has the ability to bind with the Fc portion of mammalian immunoglobulins. Previously, we reported for the first time a potent antitumor response by the inoculation of cell free Ehrlich's ascites fluid adsorbed in vitro over PA containing Staphylococcus aureus Cowan I (SAC) in Ehrlich's ascites tumor model. However, there was toxicity associated with this form of therapy in terms of early death of treated animals and the depletion of hepatic glutathione pool as well as phase I biotransformation enzyme and increase in glutathione-S-transferase (GST) activities. In the present investigation, tumor bearing animals were treated intraperitoneally (i.p.) on alternate days for 15 days with adsorbed ascites fluid (ad-ASF) (0.1 ml) and glutathione (GSH) (250 mg/kg body weight) separately. We found that GSH supplementation increases mean survival time of GSH and ad-ASF treated mice up to 37.2 days in comparison with 19.9 days for only ad-ASF treated animals, while percent increase in body weight was found to be not affected by the GSH substitution, which remains significantly lower (P < 0.01) in comparison to the tumor control animals. GSH supplementation causes a significant decrease (P < 0.05) of glutathione-S-transferase and restoration of aniline hydroxylase activity (P < 0.05) and aminopyrine-N-demethylase activity. We have also observed that GSH supplementation does not alter the tumor cell viability and tumor cell counts in ad-ASF treated animals in comparison to only ad-ASF treated animals, which indicates that GSH supplementation does not alter the antitumor effect of the therapy. Treatment of Ehrlich's ascites tumor bearing mice with ad-ASF and glutathione increased their survival, but did not reduce the mortality of animals because of tumor.

Adsorption↗

Safety and efficacy of total thyroidectomy in hands of endocrine surgery trainees.

BACKGROUND: Fear of a high complication rate of total thyroidectomy, especially in the hands of less experienced surgeons, limits its routine use. The results of total thyroidectomy in the hands of endocrine surgery trainees and consultants were compared to know whether this procedure can be performed effectively and safely by trainees. METHODS: Medical records of 232 patients who underwent total thyroidectomy from 1990 to 1997 were reviewed. Patients were put into groups A (operated by consultants) and B (trainees). Safety (postoperative hypoparathyroidism, recurrent laryngeal nerve palsy, and hemorrhage) and efficacy (postoperative radioactive iodine uptake) in the two groups were compared. RESULTS: There were 127 patients in group A and 105 in group B. Rates of occurrence of permanent hypoparathyroidism and recurrent laryngeal nerve palsy were comparable in the two groups. Postoperative radioactive iodine uptake in the two groups was not significantly different. CONCLUSIONS: Total thyroidectomy can be safely and effectively performed by endocrine surgical trainees.

Adult↗

Diagnostic evaluation of the erectile function domain of the International Index of Erectile Function.

OBJECTIVES: To evaluate the erectile function (EF) domain of the International Index of Erectile Function (IIEF) as a diagnostic tool to discriminate between men with and without erectile dysfunction (ED) and to develop a clinically meaningful gradient of severity for ED. METHODS: One thousand one hundred fifty-one men (1035 with and 116 without ED) who reported attempting sexual activity were evaluated using data from four clinical trials of sildenafil citrate (Viagra) and two control samples. The statistical program Classification and Regression Trees was used to determine optimal cutoff scores on the EF domain (range 6 to 30) to distinguish between men with and without ED and to determine levels of ED severity on the EF domain using the IIEF item on sexual intercourse satisfaction. RESULTS: For a 0.5 prevalence rate of ED, the optimal cutoff score was 25, with men scoring less than or equal to 25 classified as having ED and those scoring above 25 as not having ED (sensitivity 0.97, specificity 0.88). Sensitivity analyses revealed a robust statistical solution that was well supported with different assumed prevalence rates and several cross-validations. The severity of ED was classified into five categories: no ED (EF score 26 to 30), mild (EF score 22 to 25), mild to moderate (EF score 17 to 21), moderate (EF score 11 to 16), and severe (EF score 6 to 10). Substantial agreement was shown between these predicted and "true" classes (weighted kappa 0.80). CONCLUSIONS: The EF domain possesses favorable statistical properties as a diagnostic tool, not only in distinguishing between men with and without ED, but also in classifying levels of ED severity. Clinical validation with self-rated assessments of ED severity is warranted.

Erectile Dysfunction↗

Chemokines and chemokine receptors: their role in allergic airway disease.

One of the hallmarks of allergic pulmonary disorders is the accumulation of an abnormally large number of leukocytes including eosinophils, neutrophils, lymphocytes, basophils, and macrophages in the lung. There is now substantial evidence that eosinophils, under the control of T lymphocytes, are major effector cells in the pathogenesis of asthma. Therefore, understanding the mechanisms by which eosinophils accumulate and are activated in tissues is a fundamental question very relevant to allergic diseases. Another characteristic of allergic inflammation is the activation of leukocytes resulting in the release of biologically active mediators, such as histamine from mast cells and basophils. It is now apparent that chemokines are potent leukocyte chemoattractants, cellular activating factors, histamine releasing factors, and regulators of homeostatic immunity, making them particularly important in the pathogenesis of airway inflammation in asthma. In this regard, chemokines are attractive new therapeutic targets for the treatment of allergic disease. This article focuses on recently emerging data on the importance of chemokines and their receptors in allergic airway inflammation.

Animals↗

Acute pancreatitis associated with viral hepatitis: a report of six cases with review of literature.

Association of hepatitis viruses with acute pancreatitis in the setting of nonfulminant viral hepatitis is rare. We report six cases of nonfulminant viral hepatitis complicated by acute pancreatitis, including the first documented case of hepatitis E virus (HEV) associated acute pancreatitis. The other five patients had acute viral hepatitis caused by hepatitis A infection. Besides features of viral hepatitis, the presence of typical abdominal pain, high serum amylase, and ultrasound or CT scan features suggested the diagnosis of acute pancreatitis. This complication generally developed in the initial phase of the hepatitic illness. All of the patients had mild to moderate pancreatitis that recovered uneventfully with conservative treatment.

Acute Disease↗

Fundamental signals that regulate eosinophil homing to the gastrointestinal tract.

The histological identification of increased eosinophils in the gastrointestinal tract occurs in numerous clinical disorders; however, there is a limited understanding of the mechanisms regulating eosinophil trafficking into this mucosal surface. The results presented in this study characterize the processes regulating eosinophil homing into the gastrointestinal tract at baseline. Eosinophils were found to be present in the lamina propria of 19-day-old embryos and germ-free adult mice at concentrations comparable to those present in non-germ-free adult mice. Furthermore, eosinophil gastrointestinal levels were not altered by increasing circulating eosinophils after pulmonary allergen challenge. Gastrointestinal eosinophil levels were partially reduced in mice deficient in recombinase activating gene-1 (RAG-1), IL-5, or the beta common chain (betac), but these reductions paralleled reductions in circulating eosinophils. In contrast, mice deficient in eotaxin had a marked reduction in gastrointestinal eosinophils but normal levels of eosinophils in the hematopoietic compartments. Furthermore, eotaxin was important for regulating eosinophil levels, even in the presence of high levels of IL-5. These investigations demonstrate eosinophil homing into the gastrointestinal tract during embryonic development occurring independently of viable intestinal flora. Furthermore, eotaxin is identified as the primary regulator of eosinophil gastrointestinal homing under homeostatic states, and may therefore have a fundamental role in innate immune responses.

Allergens↗

The effects of erythromycin on the electrocardiogram.

BACKGROUND: Various cardiac electrophysiologic effects have been attributed to erythromycin. During the course of treating a pneumonia patient with IV erythromycin, the conversion of atrial fibrillation to a sinus rhythm, and its subsequent reversal, appeared to be causally related to the introduction and cessation of this antibiotic. OBJECTIVE: This observation suggested the need for studying the changes in the ECG following the use of IV erythromycin in a typical clinical setting. DESIGN: A prospective comparative drug study. SETTING: A university-affiliated teaching hospital. PATIENTS: Nineteen patients being treated for uncomplicated community-acquired pneumonia. INTERVENTION: IV erythromycin, 500 mg, and/or IV cefuroxime, 750 mg, infused in 250 mL of saline over 20 min. In the 11 patients who were receiving both of the antibiotics, cefuroxime was administered immediately before erythromycin was infused. MEASUREMENTS: The 12-lead ECG measurements were obtained before infusion, at 5-min intervals during each infusion, and at 5 and 10 min after the infusions had been completed. All of the ECG complexes and intervals were measured using a software program (Interpretive Cardiograph; Hewlett Packard; Palo Alto, CA). RESULTS: The administration of IV erythromycin increased heart rate and prolonged the corrected QT (QTc) interval. These changes were significant at 15 min of the infusion, and were no longer evident 5 min after the infusion had been stopped. The administration of IV cefuroxime did not produce any ECG changes. CONCLUSIONS: A single, standard dose of IV erythromycin prolongs the QTc interval; therefore, the drug should always be administered as a slow infusion. ECG monitoring should accompany erythromycin therapy in critically ill patients, in patients with electrolyte disorders, or in patients taking other drugs with similar cardiac effects.

Adult↗

Protein-A activates membrane bound multicomponent enzyme complex, NADPH oxidase in human neutrophils.

Protein-A, 42KD cell wall glycoprotein of S. aureus Cowan I enhance mononuclear and polymorphonuclear cell counts in vivo and possesses antitoxic, antitumor, properties. In order to explain the mechanism of its function, the respiratory burst phenomenon in cell and cell free system was studied using lucigenin-dependent chemiluminescence technique. A dose dependent increase in protein A-mediated generation of superoxide radical was observed in resting and PMA stimulated neutrophils. Superoxide dismutase (SOD) was used to confirm the production of superoxide radicals (O2-). To understand the mechanism of protein-A induced O2- generation; NADPH oxidase activity was measured in cell free system using NADPH as a substrate. A significant increase in NADPH oxidase activity was observed in the membrane and post-nuclear supernatant fraction of activated human neutrophils. Cytosolic fraction showed slight enzyme activation. Protein A (SpA)-induced NADPH oxidase activation in the membrane fraction was observed even in the absence of the substrate NADPH. These data indicate that protein A attenuate the NADPH oxidase system to produce O2- radicals.

Acridines↗

Ehrlich's ascites fluid adsorbed over protein A containing Staphylococcus aureus Cowan I produces inhibition of tumor growth.

Our earlier studies have shown that removal of various blocking factors from the sera of tumor-bearing animals and humans by adsorption over heat-attenuated and formalin-fixed-Staphylococcus aureus Cowan I (SAC) containing Protein A (PA) causes antitumor immune response. It was also shown that this procedure caused regression of a wide variety of established animal and human tumors. In the present investigation, the therapeutic potential of inoculation of ascites fluid adsorbed in vitro over non-viable SAC containing PA has been demonstrated in Ehrlich' s ascites tumor (EAT) in mouse. The antitumor effect was evident by a significant decrease in body weight (p<0.001) as well as significant reduction in viability of ascites tumor cells (p<0.001) in peritoneal cavity. However, some of the responding animals died earlier than controls, this may be due to the toxicity associated with therapy. The toxic effects were evident in decreased contents of glutathione, and increased activity of glutathione-S-transferase, decreased activity of microsomal enzymes and also in an early death of some of tumor regressed animals. The probable causes of toxicity of the therapy and prospects of reversing these toxic effects are discussed.

Albinism↗