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Biomedical subjects

A Nanda

Publications and source records attributed to A Nanda.

At least 73 records · Page 4Linked to original sources
PubMed1998

Cutaneous T-cell lymphoma with intracerebral and bilateral intraocular spread.

Brain metastasis from systemic or cutaneous lymphoma is infrequently encountered. We present a case report of cutaneous T-cell lymphoma (CTCL) that metastasized to the brain. A literature review identified fourteen other cases of brain infiltration with CTCL. This report focuses attention on the typical presentation and markedly poor prognosis that characterize this rare problem. It also emphasizes the suspicion with which a brain mass in a lymphoma patient with neurological changes should be regarded.

Aged↗
PubMed1998

Management of frontal sinus fractures with posterior table involvement: a retrospective study.

Management of frontal sinus fracture has been a matter of debate. Combined fractures of the anterior and posterior walls have been managed by various techniques, including observation, open reduction and internal fixation, ablation, obliteration, and, most recently, cranialization. The earlier techniques have met with frequent complications, including sinusitis, mucopyocele, cerebrospinal fluid leak, meningitis, and brain abscess, along with various chronic pain symptoms. Cranialization of the frontal sinus was first introduced for injuries of both walls with intracranial penetration. From 1990 to 1996, frontal sinus fractures of 11 patients (10 men and 1 woman) were treated using the cranialization procedure. Based on patient history, clinical findings, radiographic diagnoses, operative techniques, and follow-ups of these patients the authors conclude that cranialization of the frontal sinus is a safe and effective method of treating posterior table frontal sinus fractures.

Accidents, Traffic↗
PubMed1998

A method of scoring automated visual fields to determine field constriction causing blindness.

Blindness is usually defined by visual acuity criteria. Patients with markedly constricted visual fields are visually impaired even if they have good visual acuity. To our knowledge, no standardised criteria exist to determine the extent of constriction for fields done with the currently used automated static perimetry. The purpose of this study was to suggest a simple method to do so which would help in determining blindness due to field constriction. We reviewed a number of constricted visual fields obtained with Humphrey automated static perimetry. The central 30 degrees field was divided into six concentric zones. By trial and error, we devised criteria for defining visual field constriction based on absolute loss of sensitivity (< or = 0 dB) and relative loss of sensitivity (< or = 5 dB). We suggest that if a zone has at least 75% test points < or = 0 dB and no point > 10 dB, it be considered to have absolute loss of sensitivity for the purpose of defining visual field blindness. Two exceptions to this are also suggested to prevent this criterion from becoming too rigid. Examples are shown to demonstrate application of these criteria in defining blindness due to visual field constriction to < 10 degrees as suggested by the World Health Organization. Standardised determination of visual field constriction with automated perimetry could be useful in more accurate estimation of blindness in surveys, as well as in assessing eligibility for being classified as blind for legal benefits.

Blindness↗
PubMed1997

Clinical and socioeconomic profile of patients with malignant ventricular arrhythmias in 1993 to 1995. AVID investigators. Antiarrhythmics Versus Implantable Defibrillator.

This report summarizes the clinical and socioeconomic characteristics of the first 542 patients entered into the Antiarrhythmics Versus Implantable Defibrillator (AVID) trial. AVID is a multicenter trial comparing a strategy of initial implantable cardioverter-defibrillator placement to initial antiarrhythmic drug therapy in preventing death in patients resuscitated from cardiac arrest who were not taking amiodarone and who did not have an implantable cardioverter-defibrillator in place at the time of the index event. These patients were randomly assigned to immediate defibrillator placement or to "best" medical therapy. Clinical and socioeconomic histories were collected by interview using standard terms developed for the study. Patients without (group 1) and with (group 2) a history of prior cardiac arrest were compared. The mean age of the 542 patients was 65 +/- 10 years, most were men, white, had coronary disease, and were highly functional despite the fact that only a minority were employed. Almost all had some form of health insurance. At the time of the index event, few were taking any therapy to prevent cardiac arrest, even in the group of patients with a history of previous cardiac arrest. Thus, the clinical and socioeconomic profile of patients resuscitated from sudden cardiac death entered into the AVID study is generally as expected. There is a striking absence of any attempt at chronic therapy to prevent cardiac arrest in most patients with a prior ventricular tachycardia or ventricular fibrillation.

Aged↗
PubMed1997

Posterior circulation aneurysms in a child: clipping of one leads to spontaneous thrombosis of the other.

Multiple intracranial aneurysms in children are infrequent. This case involves an 11-year-old girl who presented with subarachnoid hemorrhage with posterior cerebral and superior cerebellar artery aneurysms. Initially, she underwent clipping of the posterior cerebral artery aneurysm. Four months later, she returned for clipping of the other aneurysm, at which time it was found to have completely thombosed. The literature contains 4 other cases of spontaneous thrombosis of intracranial aneurysms in children, but only one aneurysm < 25 mm in size is described. The clinical, surgical, and radiological features of this case and a detailed literature review are presented.

Adult↗
PubMed1997

Preferential inhibition of glioblastoma cells with wild-type epidermal growth factor receptors by a novel tyrosine kinase inhibitor ethyl-2,5-dihydroxycinnamate.

Epidermal growth factor receptor (EGFR) gene overexpression and mutations play an important role in the pathogenesis of a variety of malignant human cancers. In this study, we tested the effects of a novel EGFR tyrosine kinase inhibitor, ethyl-2,5-dihydroxycinnamate (EtDHC), against related human glioblastoma cell lines expressing specific forms of EGFR gene mutations. EtDHC more potently inhibited cell growth and DNA synthesis in glioblastoma cells with endogenous or overexpressed wild-type EGFR compared with those with truncated EGFR, by preferentially inhibiting the tyrosine kinase activity and autophosphorylation of the wild-type EGFR. Higher concentrations of EtDHC were required to inhibit cells expressing the truncated EGFR. These findings are the reverse of another highly specific tyrosine kinase inhibitor, tyrphostin AG 1478, which preferentially inhibited glioblastoma cells with truncated EGFR compared with those with wild-type EGFR. The differential susceptibility of various glioblastoma cells to highly specific tyrosine kinase inhibitors is significant because human gliomas are composed of heterogeneous cells with subsets of cells expressing specific gene mutations. This cellular heterogeneity could be one of the reasons why tumor cells are resistant to chemotherapy. Thus, EtDHC, especially when in combination with drugs targeting other specific gene mutations (such as tyrphostin AG 1478), holds a significant potential for chemotherapy for human glioblastomas.

Cell Division↗
PubMed1997

Design of a population-based study of visual impairment in India: The Andhra Pradesh Eye Disease Study.

Reliable population-based epidemiologic data regarding vision and ocular morbidity, as well as those about the perceptions of people regarding visual impairment and eye care, are lacking for the most part in the developing world including India. These data are the basis on which effective eye care services can be developed. To meet this need we designed the Andhra Pradesh Eye Disease Study, a population-based epidemiology study of 10,000 people in the Indian state of Andhra Pradesh. The design of this study is described in this paper. Various options for the sample size, study areas, sampling procedure, and recruitment of subjects were considered. A sample size of 10,000 people, 5,000 each in the < or = 30 and > 30 years age groups, was determined to obtain reasonable confidence in estimating the prevalence of diseases and odds ratios for risk factors of interest. A multistage sampling strategy was chosen for the study which was assumed to give a design effect of 1.5 for the estimates. One urban area, Hyderabad, and three rural areas, West Godavari, Adilabad and Mahbubnagar districts, were selected in Andhra Pradesh. Interview instruments were developed to obtain detailed information about demographic data, diet, ocular and systemic history, risk factors for eye diseases, visual function, quality of life, barriers to eye care, and knowledge about eye diseases. A detailed examination procedure was devised to obtain a broad range of normative and abnormal data related to eyes and vision. A protocol was developed for doing automated visual fields, slitlamp and fundus photography. Computer databases were made in FoxPro for data entry and subsequent analysis with SPSS. Pilot studies were done to test the instruments, procedures, and logistics of the study in urban and rural areas. Information from the Andhra Pradesh Eye Disease Study is expected to help in planning and implementation of effective long-term preventive, curative, and rehabilitative eye care services in Andhra Pradesh.

Blindness↗
PubMed1996

Tyrphostin AG 1478 preferentially inhibits human glioma cells expressing truncated rather than wild-type epidermal growth factor receptors.

The effects of a new epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, tyrphostin AG 1478, were tested on three related human glioma cell lines: U87MG, which expressed endogenous wild-type (wt) EGFR, and two retrovirally infected U87MG cell populations which over-expressed either wt (U87MG.wtEGFR) or truncated EGFR (U87MG. delta EGFR). Although AG 1478 inhibited cell growth, DNA synthesis, EGFR tyrosine kinase activity, and receptor autophosphorylation of each cell line in a dose-dependent manner, it was significantly more potent in U87MG. delta EGFR cells than in the other two cell lines. The increased inhibitory response of U87MG. delta EGFR cells was due to a greater sensitivity of the constitutively autophosphorylated Mr 140,000 and 155,000 delta EGFR species to AG 1478. These results suggest that AG 1478 is a relatively specific inhibitor of the delta EGFR, and this finding may have important therapeutic implications since the delta EGFR occurs frequently in glioblastomas and in breast, lung, and ovarian cancers.

Benzylidene Compounds↗
PubMed1996

Activation of proton pumping in human neutrophils occurs by exocytosis of vesicles bearing vacuolar-type H+-ATPases.

Proton pump activity is not measurable in the plasma membrane of unstimulated neutrophils but becomes readily detectable upon activation by soluble agonists. The mechanism of pump activation was investigated in this report. V-type H+ pump activity, estimated as a bafilomycin A1-sensitive elevation of the cytosolic pH, was stimulated in suspended neutrophils by chemotactic peptides and by phorbol esters. Stimulation of pump activity induced by the agonists was greatly enhanced by cytochalasin B, an agent known to potentiate granular secretion in neutrophils. We therefore compared the rate and extent of pump activation with the pattern of exocytosis of the four types of secretory organelles present in neutrophils, using flow cytometry and enzyme-linked immunosorbent assay. The kinetics of exocytosis of secretory vesicles and secondary and tertiary granules but not primary granules paralleled the appearance of pump activity. The subcellular localization of the pump was defined by cellular fractionation and immunoblotting using an antibody to the C subunit of the V-type ATPase. The pump was abundant in tertiary granules, with significant amounts present also in primary granules and secretory vesicles. The pump was scarce in secondary granules and not detectable in the cytosol. Finally, the agonists failed to stimulate pump activity in neutrophil cytoplasts, which are intact cell fragments devoid of acidic granules. Together, our results suggest that the V-type H+-ATPase is not constitutively present in the plasma membrane of neutrophils but is delivered to the surface membrane by exocytosis during cellular activation. Tertiary granules and secretory vesicles are the most likely source of V-ATPases. Following insertion in the plasma membrane, the pump is poised to effectively extrude the excess metabolic acid that is generated during chemotaxis and bacterial killing.

Enzyme Activation↗
PubMed1996

Metastatic disease in the cerebellum. The LSU experience in 1981-1993.

We retrospectively determined the outcome of management of metastatic disease in the cerebellum (MDC) in 45 patients because MDC is considered to be more immediately life-threatening than metastases in other intracranial locations. Treatment consisted of tumor resection and radiotherapy (RR; n = 11) or of radiotherapy alone (RA; n = 34). Significant differences in the median survival (15 months for RR and 3 months for RA, p = 0.005) and in survival rates at 1 year (61 +/- 30% for RR and 9 +/- 10% for RA, p < 0.001) and at 2 years (15 +/- 22% for RR and 0% for RA, p < 0.05) were noted. This combined management program of surgery followed by radiotherapy for MDC produced a worthwhile gain in survival.

Aged↗
PubMed1995

Chemoattractant-induced activation of vacuolar H+ pumps and of an H(+)-selective conductance in neutrophils.

Upon binding to their receptors on the surface of neutrophils, chemotactic peptides elicit a burst of metabolic activity. The excess acid generated by this burst must be rapidly extruded in order to maintain intracellular pH and preserve normal microbicidal responses. Recently, H(+)-pumping vacuolar-type ATPases (V-pumps) and a H(+)-selective conductance were described in the membrane of neutrophils. However, these systems are virtually quiescent in resting cells. In this report, we analyzed whether the V-pumps and the conductance become active and contribute to pH regulation following cell activation by chemoattractants. Formyl-Met-Leu-Phe (fMLP) was found to stimulate V-pumps, as assessed by the appearance of bafilomycin-sensitive H+ extrusion. Concomitantly, the chemoattractant also activated the H+ conductance, detected as a voltage-dependent and Zn(2+)-sensitive net H+ efflux. In both cases, activation was prevented by treatment with competing antagonistic peptides or with pertussis toxin, implying mediation by a receptor coupled to a heterotrimeric G protein. The signalling pathways downstream of the G proteins were also investigated. Stimulation of neither the V-pump nor the conductance required activation of protein kinase C. An elevation of cytosolic calcium ([Ca2+]i) comparable to that induced by fMLP did not suffice to trigger either transporter. Moreover activation of the conductance remained unaffected when the chemoattractant-induced increase in [Ca2+]i was precluded. In contrast, stimulation of the V-pump was substantially (approximately 50%) depressed when [Ca2+]i was prevented from rising. Tyrosine phosphorylation of several polypeptides accompanies stimulation by fMLP. Prevention of phosphotyrosine accumulation resulted in a pronounced inhibition of H(+)-pumping and of the H+ conductance. Together, these data indicate that engagement of surface receptors by chemotactic peptides can lead to stimulation of two voltage-sensitive pH regulatory pathways, a pump and a conductance, by a pathway that requires tyrosine phosphorylation. Both pathways are capable of sizable H+ extrusion, thereby contributing to pH regulation during the metabolic burst.

Calcium↗
PubMed1995

Head and neck squamous cell carcinoma metastatic to the orbital apex.

Primary squamous cell carcinoma of the head and neck most commonly metastasizes to the lymph nodes, lung, bone, and liver. Many other rare sites of metastatic disease have been reported. To date, metastatic squamous cell carcinoma of the head and neck to the orbital apex has not been described. Presented are two cases, one tonsil and one parotid primary with metastatic disease to the orbital apex. Many tumors have been found to metastasize to the eye and orbit, but head and neck neoplasms are rarely reported. A review of the literature is presented in addition to the detailed case reports with their radiologic findings and clinical course. Surgical resection followed by postoperative radiotherapy appears the treatment of choice at this time.

Case Reports↗
PubMed1994

Assessment of the contribution of the cytochrome b moiety of the NADPH oxidase to the transmembrane H+ conductance of leukocytes.

Phagocytic cells can kill microorganisms by synthesizing superoxide. Activation of the NADPH oxidase that generates superoxide is accompanied by a large intracellular burst of metabolic acid production. Despite the excess acid generation, cytosolic pH (pHi) remains near neutrality due to the concomitant stimulation of several homeostatic H+ extrusion mechanisms including a recently described H(+)-conductive pathway. Activation of the conductance by phorbol esters is defective in neutrophils of chronic granulomatous disease (CGD) patients lacking the transmembrane cytochrome b subunits of the NADPH oxidase. This finding suggests that the oxidase itself undertakes H+ translocation or that, alternatively, assembly of the oxidase is required to activate a separate H+ conducting entity. To distinguish between these possibilities, the presence of the conductive pathway was assessed in unstimulated normal and CGD cells by manipulating pHi and the transmembrane potential. Using fluorimetric determinations of pHi, a conductive, Zn(2+)-sensitive alkalinization was observed in neutrophils from both normal and cytochrome b-deficient CGD donors. The electrophysiological properties of the conductance were defined in purified blood monocytes using the whole cell configuration of the patch clamp. Depolarizing pulses induced slowly activating outward currents in cells from both normal and cytochrome b-deficient individuals. The elicited currents were potentiated by cytosolic acidification and did not inactivate within the times tested. As in control leukocytes, the reversal potential of tail currents in the CGD cells closely approximated the H+ equilibrium potential and was unaffected by substitution of the major ionic components of the external bathing medium. At all voltages tested, the magnitude of the evoked currents was comparable in normal and CGD cells. The results indicate that, like macrophages and granulocytes, human monocytes display a voltage-gated highly H(+)-selective conductance. More importantly, our findings imply that the conductive pathway is present in cells devoid of cytochrome b. Therefore, the defective activation of the conductive pathway by protein kinase C agonists in CGD cells is not due to the physical absence of the transporter. Instead we propose that the oxidase functions in a regulatory capacity, facilitating the opening of a distinct H+ conductance during cellular stimulation.

Biological Transport↗