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Biomedical subjects

M Nash

Publications and source records attributed to M Nash.

At least 19 recordsLinked to original sources
PubMed1998

Competitive binding of xenobiotic oestrogens to rat alpha-fetoprotein and to sex steroid binding proteins in human and rainbow trout (Oncorhynchus mykiss) plasma.

The ability of a variety of "environmental oestrogens" to compete with radiolabelled steroids to rat alpha-fetoprotein (AFP) and to sex steroid binding proteins was investigated in human and rainbow trout (Oncorhynchus mykiss) plasma. For [3H]oestradiol binding to AFP, diethylstilbestrol and 4-nonylphenoxyacetic acid showed significant competition at concentrations about 100-fold greater than oestradiol (relative binding affinities approximately 1% c.f. oestradiol). All other compounds (phytooestrogens: coumestrol, daidzein, genistein; others: 4-nonylphenol, 4-tert-octylphenol, 4-nonylphenoldiethoxylate, 4-tert-butylphenol, bisphenol-A (Bis-A), bis(2- ethylhexl)phthalate, dioctylphthalate, dibutyl phthalate, 2, 4'DDT (op' enantiomer), 2,4'-DDE (mixed enantiomers), kepone) showed only very weak or no competition (relative binding affinities <<0.1% c.f. oestradiol). The situation for both human and fish plasma was very similar, with only very high concentrations (>>1000 fold more than the natural ligand) of a few of the compounds showing any ability to displace the natural ligand. These results suggest that environmental oestrogenic agents are unlikely to produce biological effects by displacing endogenous steroids from plasma steroid binding proteins unless they are present in very high concentrations.

Animals↗
PubMed1997

Prognostic significance of fluorescence intensity of surface marker expression in childhood B-precursor acute lymphoblastic leukemia. A Pediatric Oncology Group Study.

This report describes the prognostic significance of the intensity of surface membrane antigen expression in a series of 1,231 children older than 1 year with newly diagnosed B-precursor acute lymphoblastic leukemia (ALL) treated on Pediatric Oncology Group (POG) treatment protocols. All patients had dual-color flow cytometric immunophenotyping performed at a central reference laboratory with a standard panel of monoclonal antibodies. The flow cytometers used in the study were calibrated with a standard fluorescence microparticle that permitted conversion of relative fluorescence channels to standard units of mean equivalents of soluble fluorochrome (MESF). In univariate analysis, fluorescence intensity of CD45 and CD20 was significantly associated with event-free survival (EFS), whereas other markers showed no significant correlation with outcome. Patients whose blasts were greater than the 75th percentile of intensity for CD45 (corresponding to 18,000 MESF units with CD45-FITC, or about 8% of the intensity of normal lymphocytes) fared significantly worse than those with lower-density CD45, and those whose blasts were greater than the 25th percentile of intensity for CD20 (corresponding to 17,900 MESF units with CD20-PE) had a poorer EFS. The intensity of both CD45 and CD20 was independently correlated with outcome. There was no significant correlation between intensity of expression of either antigen and traditional clinical risk factors, ploidy, or t(9;22) or t(1;19). All patients with t(4;11) had CD45 intensity greater than the 75th percentile, but CD45 intensity retained its prognostic significance after adjusting for t(4;11). In multivariate analysis, both CD45 intensity greater than the 75th percentile and CD20 intensity greater than the 25th percentile were significantly correlated with poor outcome independently of previously reported poor prognostic factors including National Cancer Institute (NCI) risk group, ploidy, trisomies of 4 and 10, and adverse translocations including t(1;19), t(9;22), and t(4;11). We conclude that in childhood B-precursor ALL, the intensity of expression of CD20 and CD45 provides prognostic information not available from simple consideration of antigen expression as positive or negative, and adds to that obtained from traditional clinical and biologic risk factors.

Adolescent↗
PubMed1997

Low-velocity gunshot wounds to the paranasal sinuses.

There are more than 200 million private firearms in the United States today. Firearm-associated deaths are the second leading cause of mortality for men 1 to 38 years of age. There are many studies in the literature concerning the management of high-velocity gunshot injuries to the head and neck. However, there are no studies in the English language literature concerning the management of isolated low-velocity gunshot wounds to the paranasal sinuses. We retrospectively reviewed 35 patients treated for low-velocity gunshot wounds of the paranasal sinuses between 1985 and 1994 at Kings County Hospital Center. The injuries sustained by these patients were less severe than previously reported for high-velocity missile or shotgun injuries. The management of these injuries is outlined with emphasis on (1) indications for angiographic studies, (2) airway management, and (3) indications for operative removal of bullet fragments.

Adolescent↗
PubMed1996

Endothelial dysfunction late after Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is a systemic vasculitis of childhood with widespread vascular endothelial damage in the acute stage. Long-term complications, such as myocardial infarction and death, are recognized, but the extent and nature of late vascular abnormalities that might predispose to these events have not been studied. METHODS AND RESULTS: We used high-resolution ultrasound to study endothelial function in the brachial artery of 20 patients 5 to 17 years after acute KD (median, 11 years) and compared findings with those in 20 age- and sex-matched control subjects. Vascular responses to reactive hyperemia (with flow increase leading to endothelium-dependent dilation) and to sublingual glyceryl trinitrate (GTN; endothelium-independent dilation) were recorded. The relationship between endothelium-dependent vascular responses and features of the endothelium acute illness was examined. There was no difference in baseline vessel diameter, degree of reactive hyperemia, or response to GTN between patients and control subjects. In contrast, flow-mediated dilation was markedly reduced in KD patients compared with control subjects (3.1% versus 9.4%; P < .001). Late endothelium-dependent responses were not related to features of the acute illness. CONCLUSIONS: Abnormalities of systemic endothelial function are present many years after resolution of acute KD, even in patients without detectable early coronary artery involvement. Because this may be an important factor in the genesis of late vascular complications, long-term follow-up of all patients with KD is indicated.

Adolescent↗
PubMed1996

DNA index of glial tumors in children. Correlation with tumor grade and prognosis.

BACKGROUND: Although DNA index (DI) has prognostic significance in a variety of pediatric malignancies, there are few data regarding its utility in central nervous system (CNS) tumors. We have previously shown that patients with hyperdiploid medulloblastoma have a significantly better survival than those whose tumors are diploid. Here, we examine the effect of DI and tumor grade on the progression free survival (PFS) of 57 patients with a variety of glial neoplasms. METHODS: DI was determined by flow cytometry on freshly obtained tumor tissue from the initial diagnostic specimens; a DI = 1.0 was defined as diploid (DIP), 1.0 < DI < 1.1 as near diploid (NDIP), and DI > 1.1 as hyperdiploid (HYP). Tumors were histologically graded according to the World Health Organization classification. RESULTS: There were 21 Grade I tumors, 20 Grade II, 8 Grade III, and 8 Grade IV. Among the 41 low grade tumors (Grade I-II), 39 were DIP or NDIP, and 2 were HYP. Among the 16 high grade tumors (Grade III-IV), 9 were DIP, 2 NDIP, and 5 HYP. The 4-year PFS of low grade tumors was 70% (standard deviation [SD] 12%) versus 8% (SD 7%) for high grade tumors. There was a significant correlation between low grade tumor histology and a DIP/NDIP DI (P = 0.015), and univariate analysis suggested improved PFS was associated with DIP/NDIP tumors (P = 0.05). However, DI did not remain a significant prognostic factor after being stratified by tumor grade (P = 0.87). CONCLUSIONS: Unlike medulloblastoma, DI is not an independent prognostic factor in pediatric glial tumors.

Adolescent↗
PubMed1996

Safety awareness for the otolaryngologist caring for the HIV-positive patient.

The alarming increase in human immunodeficiency virus (HIV) infection, expected to reach 40 million cases worldwide by the year 2000, has enormous impact on the otolaryngologist, since up to 70% of HIV-positive patients present with head and neck symptoms. Parenteral and nonparenteral acquisition of HIV has been documented with seroconversion from needle sticks estimated at 1 for every 200 exposures. The rate of compliance with universal precautions is found to be reported as low as 16%. In 1993, over 1400 patients with HIV were admitted to Kings County Hospital Center. There were 165 reported cases of sharp injuries of which 4 were scalpel related and 17 were suture needle related. We surveyed HIV safety experiences at five hospitals emphasizing operating room procedures, including instrument handling, gloving, elimination of excess equipment and personnel, utilization of nonsharp instruments, and team discipline. Preventive measures are recommended to help minimize inadvertent sharp injuries.

HIV Infections↗
PubMed1996

Regional spread of auricular and periauricular cutaneous malignancies.

Over 90% of all cutaneous malignancies occur in the head and neck. Malignancies involving the external auditory meatus, auricle, and periauricular region are notoriously difficult to control. The morbidity and mortality associated with extension of these malignancies underscore the importance of complete initial removal. We present 14 patients who underwent excision of periauricular lesions. All lesions were less than 2 cm in diameter and previously excised with negative margins. These patients were subsequently referred for regional disease. Twenty-nine percent of the patients failed definitive surgical therapy. We examine the indications for regional lymphadenectomy in the treatment of auricular and periauricular cutaneous malignancies.

Aged↗
PubMed1996

Laryngeal tuberculosis in HIV-infected patients: a difficult diagnosis.

Unrecognized laryngeal tuberculosis (TB) poses a significant hazard to otolaryngologists. However, the changing manifestations of TB in patients with human immunodeficiency virus (HIV) infection can make its diagnosis difficult. In our population of 146 patients with TB involving the head and neck, HIV infection was present in 70 cases (48%). The prevalence of laryngeal TB in this population was 5.5% (8 patients). Concomitant HIV infection was present in 2 (25%) of 8 patients with laryngeal TB. A delay in the diagnosis of laryngeal TB occurred in 100% of patients with HIV infection, compared with 17% of non-HIV-infected patients (P = .055). The cause of the delayed diagnosis was multifactorial, mainly the presence of multiple confounding variables and the carcinoma-like appearance of the laryngeal TB lesions in HIV-infected patients. To reduce risk for transmission of TB to health care providers, a high level of suspicion must be present for all patients with laryngeal lesions, especially those with HIV infection.

Adult↗
PubMed1995

Acute postobstructive pulmonary edema.

Acute postobstructive pulmonary edema may occur after airway obstruction. A decrease in intrathoracic and intraalveolar pressures causes an increased blood flow into the pulmonary vasculature and favors the development of pulmonary edema. Two mechanisms for the development of acute postobstructive pulmonary edema are proposed: type 1 follows acute airway obstruction, and type 2 follows relief of chronic airway obstruction.

Acute Disease↗
PubMed1994

Metabolism and disposition of 14C-granisetron in rat, dog and man after intravenous and oral dosing.

1. The disposition and metabolic fate of 14C-granisetron, a novel 5-HT3 antagonist, was studied in rat, dog, and male human volunteers after intravenous and oral administration. 2. Complete absorption occurred from the gastrointestinal tract following oral dosing, but bioavailability was reduced by first-pass metabolism in all three species. 3. There were no sex-specific differences observed in radiometabolite patterns in rat or dog and there was no appreciable change in disposition with dose between 0.25 and 5 mg/kg in rat and 0.25 and 10 mg/kg in dog. Additionally, there were no large differences in disposition associated with route of administration in rat, dog and man. 4. In rat and dog, 35-41% of the dose was excreted in urine and 52-62% in faeces, via the bile. Metabolites were largely present as glucuronide and sulphate conjugates, together with numerous minor polar metabolites. In man, about 60% of dosed radioactivity was excreted in urine and 36% in faeces after both intravenous and oral dosing. Unchanged granisetron was only excreted in urine (5-25% of dose). 5. The major metabolites were isolated and identified by MS spectroscopy and nmr. In rat, the dominant routes of biotransformation after both intravenous and oral dosing were 5-hydroxylation and N1-demethylation, followed by the formation of conjugates which were the major metabolites in urine, bile and plasma. In dog and man the major metabolite was 7-hydroxy-granisetron, with lesser quantities of the 6,7-dihydrodiol and/or their conjugates.

Administration, Oral↗
PubMed1994

Do electrolyte-containing beverages improve water imbalance in hyponatremic schizophrenics?

BACKGROUND: To determine if ready access to a sodium-containing beverage ameliorates life-threatening water imbalance, we compared Gatorade to water in an ABA design. METHOD: Four male chronic schizophrenic inpatients with symptomatic hyponatremia drank water for 1 week, Gatorade plus water for 3 weeks, and then water again for 1 week. Afternoon plasma osmolality and morning serum sodium levels were used to estimate hydration status, and morning and afternoon urine creatinine concentrations were used to estimate fluid intake. RESULTS: During the baseline phase, subjects were mildly polydipsic and mildly overhydrated in the morning and severely overhydrated in the afternoon. All subjects stated they preferred Gatorade and appeared to consume large quantities of it. Indices of fluid intake and hydration status did not differ between the two control phases, nor between the treatment phase and the other two phases. Frequency of severe hypo-osmolemia was also unaffected. CONCLUSION: Substitution of electrolyte-containing beverages is not likely to prevent water intoxication.

Adult↗
PubMed1993

Serotonergic, 5-HT2, receptor-mediated phosphoinositide turnover and mobilization of calcium in cultured rat retinal pigment epithelium cells.

Cultured rat retinal pigment epithelium cells are shown to contain serotonergic, 5-HT2, receptors associated with phosphoinositide turnover and mobilization of intracellular calcium. Serotonin at a concentration of 10 microM induced a 2.5-fold increase in [3H]-inositol phosphates (more than 75% is in the form of [3H]-inositol-1-phosphate) accumulation within 30 min in cells preincubated in [3H]-myo-inositol and exposed to 5 mM lithium chloride. The EC50 value of serotonin was approx. 0.9 microM and the saturation concentration was 100 microM. Serotonin analogues like tryptamine, 5-methoxytryptamine, alpha-methyl-serotonin and the 5-HT2 agonists quipazine and DOI (1-[2,5-dimethoxy-4-iodophenyl]-2-aminopropane) all stimulated InsPs accumulation to some degree. Carbachol, noradrenaline, isoproterenol, dopamine, tryptophan, 5-hydroxytryptophan, 8-hydroxy-2(di-n-propyl-amino) tetralin, 2-methyl-serotonin and NECA (5'-[N-ethyl]-carboxamidoadenosine) were inactive. The serotonin-induced response was blocked most effectively by ketanserin and methysergide but not by 5-HT3 or 5-HT1 antagonists. The serotonin response was attenuated by the active phorbol ester, 4 beta-phorbol 12-myristate 13-acetate and this was attenuated by the non-selective protein kinase C inhibitor, staurosporine. Pertussis toxin failed to influence the serotonin-mediated phosphoinositide turnover. Addition of serotonin to cultures loaded with Fura-2 showed a transient increase in calcium concentrations in most of the cells. This change in calcium was independent of external calcium and the serotonin response was attenuated by ketanserin but not by the 5-HT3 antagonist granisetron.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

On the origin of Alzheimer's disease: a hypothesis.

There is no unifying hypothesis to account for the anatomical distribution of neuropathology, the involvement of beta-amyloid precursor protein (beta APP) and the role of increasing age in triggering the Alzheimer disease process. We report here that layer II pre-alpha neurones in transentorhinal and entorhinal cortex contain more beta APP immunoreactivity than other cortical neurones in normal individuals. This immunoreactivity increased in the early stages of Alzheimer's disease and was lost as the disease progressed. These neurones are known to undergo genetically programmed re-sprouting and synaptogenesis during the fifth and sixth decades of life. We hypothesize that these phenomena are related and that the Alzheimer's disease process originates in entorhinal cortex neurones due to the enhancement of their normally high content of beta APP during age-related resprouting.

Adult↗
PubMed1992

Epidermal growth factor potentiates the transmitter-induced stimulation of C-AMP and inositol phosphates in human pigment epithelial cells in culture.

Salbutamol, isoproterenol and dopamine stimulate C-AMP production in human retinal pigment epithelium (RPE) cells by activation of beta 2-type receptors. Epidermal growth factor (EGF) in contrast does not alter basal levels of C-AMP but elevates in an apparently dose-dependent manner the isoproterenol-induced stimulation of C-AMP. EGF also potentiates the forskolin-induced stimulation of C-AMP but has no effect on the elevation of C-AMP caused by NECA (5'-[N-ethyl]-carboxamido adenosine), an adenosine A2-receptor agonist. EGF, isoproterenol and NECA have no effect on basal levels of inositol phosphates (InsPs) in human RPE cells, but EGF specifically elevates the carbachol-induced stimulation of InsPs. The carbachol effect on InsPs is attenuated by the phorbol ester PMA (4 beta-phorbol 12 myrisate 13-acetate). PMA did not, however, affect the stimulation of C-AMP caused by isoproterenol. The interaction of EGF and C-AMP is further demonstrated in experiments where the incorporation of [3H]thymidine into RPE cells was studied, as an index for proliferation. EGF stimulates RPE cell proliferation while isoproterenol and dibutyryl C-AMP nullify the EGF effect. Dibutyryl C-AMP has a negative effect on RPE cell proliferation while isoproterenol is ineffective. The data presented here suggest that after stimulation of EGF receptors, tyrosine-kinase-activated products can influence secondary messenger products produced from activation of beta 2-type (linked with C-AMP formation) and muscarinic (linked with InsPs production) receptors in RPE cells. We could find no evidence of an interaction between receptors associated with C-AMP and InsPs/diacylglycerol production.

Adolescent↗
PubMed1992

The transcervical approach to the superior mediastinum.

We describe our experience with the transcervical approach for the surgical treatment of nonthyroidal superior mediastinal masses. With careful patient selection, proper preoperative workup, and proper operative positioning and technique, the entire superior mediastinum may be explored, thus avoiding the significant morbidity associated with the transsternal route. The transcervical approach requires a thorough knowledge of the surgical anatomy. Nine patients underwent transcervical exploration of the superior mediastinum. The indications included parathyroid adenoma, thymoma, congenital cyst, hemangioma, adenocarcinoma, and thymectomy for myasthenia gravis. We specifically discuss the role of thymectomy in the treatment of myasthenia gravis.

Adult↗