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Biomedical subjects

A Mishra

Publications and source records attributed to A Mishra.

At least 55 records · Page 3Linked to original sources
PubMed2001

Gastrointestinal eosinophils.

The gut-associated lymphoid tissue (GALT) is composed of lymphocytes residing in Peyer's patches, lamina propria, and intraepithelial compartments. In addition to these features which distinguish GALT from other peripheral sites of the immune system, the gastrointestinal immune system is also composed of resident eosinophils. Eosinophils are generally considered to be peripheral blood leukocytes that have an important pro-inflammatory role in various immune disorders. Although most research concerning this cell has focused on understanding its trafficking and function in the blood and lung, recent studies have also started to elucidate its regulation and function in the gastrointestinal tract. Interestingly, eosinophil numbers in the gastrointestinal tract are substantially higher than in other tissues. At baseline (healthy conditions), most eosinophils reside in the lamina propria in the stomach and intestine. Eosinophil homing to these sites occurs during embryonic development and their levels in perinatal mice are comparable to those in adults, indicating that their homing is not dependent upon the presence of intestinal flora. Furthermore, eosinophil localization to the lamina propria at baseline is critically regulated by eotaxin, a chemokine constitutively expressed throughout the gastrointestinal tract. Although eotaxin is required for eosinophil homing, its expression in the esophagus is not sufficient for eosinophil accumulation, since this organ is devoid of eosinophils at baseline. During Th2-associated inflammatory conditions (e.g. interleukin (IL)-5 overexpression or oral allergen challenge), marked increases of eosinophils occur not only in the lamina propria but also in Peyer's patches. The accumulation of Peyer's patch eosinophils, which mainly occurs in the outer cortex and interfollicular regions, is critically regulated by IL-5 and less significantly by eotaxin, suggesting the involvement of other eosinophil chemokines in this lymphoid compartment. Preliminary investigations have shown that gastrointestinal eosinophils express the alpha4beta7 integrin and that this molecule is responsible, in part, for eosinophil homing. In summary, eosinophils are resident cells of the gastrointestinal immune system whose levels can be induced by antigen exposure under Th2 conditions, in a manner that is critically regulated by eotaxin and IL-5. We propose that eosinophils are integral members of the gastrointestinal immune system and are likely to be important in innate, regulatory and inflammatory immune responses.

Administration, Oral↗
PubMed2001

A pathological function for eotaxin and eosinophils in eosinophilic gastrointestinal inflammation.

Although eosinophils have been implicated in the pathogenesis of gastrointestinal disorders, their function has not been established. Using a murine model of oral antigen-induced eosinophil-associated gastrointestinal disease, we report the pathological consequences of eosinophilic inflammation and the involvement of eotaxin and eosinophils. Exposure of mice to enteric-coated antigen promotes an extensive T helper 2-associated eosinophilic inflammatory response involving the esophagus, stomach, small intestine and Peyer's patches as well as the development of gastric dysmotility, gastromegaly and cachexia. Electron microscopy shows eosinophils in proximity to damaged axons, which indicated that eosinophils were mediating a pathologic response. In addition, mice deficient in eotaxin have impaired eosinophil recruitment and are protected from gastromegaly and cachexia. These results establish a critical pathological function for eotaxin and eosinophils in gastrointestinal allergic hypersensitivity.

Administration, Oral↗
PubMed2001

Functioning adrenal tumours in children and adolescents: an institutional experience.

BACKGROUND: The purpose of the present paper was to carry out an audit of clinicopathological profile and treatment outcome in 13 children with functioning adrenal tumours. METHODS: The medical records of 13 children with functioning adrenal tumours who were managed between June 1990 and January 1999 were reviewed. Demographic data, clinical features, biochemical and localization studies, operative details and follow-up records were studied. Children with neuroblastoma were excluded. RESULTS: The mean age was 7.4 +/- 5.3 years. Seven patients had Cushing's syndrome (CS), two patients had virilizing tumours, three patients had phaeochromocytoma (PCC) and one patient had Conn's syndrome. All patients (except one child with CS) were treated surgically. Two children with adrenocortical carcinoma (ACCa) died during the perioperative period. Histopathological diagnosis was adrenal cortical adenoma (ACAd) in four patients, ACCa in five patients and PCC in three patients. Two ACCa patients died of metastases at 12 and 14 months, respectively, while the third is alive and well at 30 months. Children with ACAd are alive and well at 91, 56, 32 and 27 months postoperatively. Children with PCC are free of disease (normal urinary metanephrines) at 63, 18 and 8 months after surgery but require antihypertensive drugs in low doses. CONCLUSION: The outcome of surgery is good in cases of ACAd and PCC. Although outcome is poor in ACCa, surgery remains the mainstay of treatment and offers good palliation.

Adolescent↗
PubMed2001

IL-13 induces eosinophil recruitment into the lung by an IL-5- and eotaxin-dependent mechanism.

BACKGROUND: IL-13 induces several characteristic features of asthma, including airway eosinophilia, airway hyperresponsiveness, and mucus overproduction; however, the mechanisms involved are largely unknown. OBJECTIVE: We hypothesized that IL-13-induced inflammatory changes in the lung were dependent in part on IL-5 and eotaxin, two eosinophil-selective cytokines. METHODS: Recombinant murine IL-13 was repeatedly administered to the lung by intranasal delivery until the characteristic features of asthma developed. To analyze the role of IL-5 and eotaxin, we subjected eotaxin gene-targeted, IL-5 gene-targeted, eotaxin/IL-5-double-deficient, IL-5 transgenic, and wild-type mice of the Balb/C background to the experimental regime. RESULTS: The induction of IL-13-mediated airway eosinophilia was found to occur independently of eosinophilia in the blood or bone marrow, indicating that IL-13-induced airway inflammation is primarily mediated by local effects of IL-13 in the lung. Eosinophil recruitment into both the lung tissue and bronchoalveolar lavage fluid was markedly attenuated in IL-5-deficient mice in comparison with wild-type controls. Accordingly, IL-13 delivery to IL-5 transgenic mice resulted in a large increase in airway eosinophils in comparison with wild-type mice. Interestingly, IL-13-induced eosinophilia in the bronchoalveolar lavage fluid of eotaxin-deficient mice was not impaired; however, these same mice failed to mount a significant tissue eosinophilia in response to IL-13. Finally, IL-13-induced mucus production was not affected by the presence of IL-5 or eotaxin, suggesting that IL-13-induced mucus secretion is mechanistically dissociated from airway eosinophilia. CONCLUSION: Selective components of the IL-13-induced asthma phenotype--airway eosinophilia but not mucus secretion--are differentially regulated by IL-5 and eotaxin. IL-5 is required for IL-13 to induce eosinophilia throughout the lung, whereas eotaxin regulates the distribution of airway eosinophils.

Animals↗
PubMed2001

Olfaction and its alteration by nasal obstruction, rhinitis, and rhinosinusitis.

The sense of smell has been largely ignored by otorhinolaryngologists, even though 1) its medical stewardship falls within their specialty's purview, 2) olfactory dysfunction is not uncommon in the general population, and 3) disorders of olfaction have significant quality of life, nutritional, and safety consequences. This report provides a succinct overview of the major intranasal neural systems present in humans (namely, cranial nerves O, I, and V, and the nonfunctional accessory [vomeronasal] organ system), along with a summary of notable findings resulting from the application of modern olfactory tests to patient populations, emphasizing diseases of the nose. Such tests have led to the discovery of significant influences of age, gender, smoking, toxic exposure, and genetics on the ability to smell. Within the field of otorhinolaryngology, they have revealed that 1) surgical and medical interventions in patients with rhinosinusitis do not, on average, lead to complete recovery of olfactory function, despite common beliefs to the contrary, and 2) associations are generally lacking between measures of airway patency and olfactory function in such cases. These findings have thrown into question the dogma that olfactory loss in rhinosinusitis is attributable primarily to blockage of airflow to the receptors and have led to histopathological studies demonstrating significant olfactory epithelial compromise in sinonasal syndromes.

Cranial Nerves↗
PubMed2001

An etiological role for aeroallergens and eosinophils in experimental esophagitis.

Eosinophil infiltration into the esophagus is observed in diverse diseases including gastroesophageal reflux and allergic gastroenteritis, but the processes involved are largely unknown. We now report an original model of experimental esophagitis induced by exposure of mice to respiratory allergen. Allergen-challenged mice develop marked levels of esophageal eosinophils, free eosinophil granules, and epithelial cell hyperplasia, features that mimic the human disorders. Interestingly, exposure of mice to oral or intragastric allergen does not promote eosinophilic esophagitis, indicating that hypersensitivity in the esophagus occurs with simultaneous development of pulmonary inflammation. Furthermore, in the absence of eotaxin, eosinophil recruitment is attenuated, whereas in the absence of IL-5, eosinophil accumulation and epithelial hyperplasia are ablated. These results establish a pathophysiological connection between allergic hypersensitivity responses in the lung and esophagus and demonstrate an etiologic role for inhaled allergens and eosinophils in gastrointestinal inflammation.

Administration, Intranasal↗
PubMed2001

Cost-effective diagnostic nasal endoscopy with a modified otoscope.

We present 'Mishra's rhinoscope', a novel, cost-effective technique of zero-degree rigid nasoendoscopy with a modified otoscope, the results of which are comparable with the fibreoptic sinoscope. This is particularly suited for the developing world where financial constraints restrict the diagnosis of an occult nasal pathology.

Cost-Benefit Analysis↗
PubMed2001

Prolonged, symptomatic hypocalcemia with pamidronate administration and subclinical hypoparathyroidism.

A 62-yr-old woman with thyroid carcinoma metastatic to bone, and a history of subclinical hypoparathyroidism was admitted to the hospital in hypocalcemic crisis 5 wk after receiving iv pamidronate. The patient had tetany and laryngospasm. An electrocardiogram showed junctional rhythm with QT segment prolongation. The patient had previously maintained a low-normal serum calcium on 500-750 mg of calcium carbonate and 600 IU of vitamin D daily. One week after pamidronate administration the patient's calcium and vitamin D supplementation were inadvertently discontinued. She continued to take daily intranasal calcitonin. At the time of her hospitalization for hypocalcemia, the patient's serum calcium was 4.3 mg/dL. The patient received aggressive calcium and vitamin D supplementation. However, her serum calcium remained below 6 mg/dL for a 2-wk period, and took another week to return to the normal range. In this article, we discuss the counterregulatory responses necessary to maintain calcium homeostasis following osteoclast inhibition by bisphosphonates. We also review the risk factors for hypocalcemia following bisphosphonate administration. Pamidronate and other bisphosphonates are becoming an integral part of the management of normocalcemic patients with malignant bone disease. Therefore, awareness of risk factors for hypocalcemia and familiarity with avenues available for protection from potentially catastrophic hypocalcemia are both crucial.

Antineoplastic Agents↗
PubMed2001

Medulloblastomas of the cerebellopontine angle.

It is unusual for a medulloblastoma to occur in the cerebellopontine angle (CPA). Four of the total 63 cases of medulloblastoma managed in our department between 1988 to 1998, presented with a mass in the cerebellopontine angle. There were two children amongst these four patients, aged eight and nine years. The other two patients were young adults. Three patients had primary CPA medulloblastoma, while the fourth case had a recurrence in this region, following the excision of the primary vermian tumour. All the four cases were managed by gross total microsurgical excision and craniospinal irradiation. One of the two children, developed subfrontal recurrence after 1 year and 8 months of initial treatment, while the other child developed a large recurrence at primary site, within three months of post-operative irradiation. However, the adult patient developed CPA recurrence and subsequent cervical intramedullary metastasis within two and a half years of diagnosis. These three cases succumbed to their disease, between three months to thirty months of their initial management. However the fourth patient, a 20 years female with desmoplastic variant, was well at two and a half years of follow up.

Adult↗
PubMed2001

A fatal case of systemic brucellosis.

A 65 years man presented with fever, drenching sweats, progressive dyspnoea, backache and weight loss. On examination, he had wide pulse pressure, clubbing, retinal hemorrhages, aortic and mitral regurgitation, hepatosplenomegaly, lower spinal tenderness and bilateral basal crepitations. Transthoracic 2D-echocardiography showed a large vegetation on the aortic valve. Antibody titers for brucella were positive. X-ray spine was suggestive of brucella spondylitis. Early surgical intervention was planned and the patient was given combination antibiotic therapy. The course was complicated by renal failure and the patient succumbed while being taken up for surgery.

Aged↗