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Biomedical subjects

M Geller

Publications and source records attributed to M Geller.

At least 37 records · Page 2Linked to original sources

Posterior fossa tumors in children: a case study.

Brain tumors are the second most common malignancy to occur during childhood and the posterior fossa is the most common region of the brain affected. Diagnosis and treatment are complex and challenging. Once a child suffering from a posterior fossa tumor is identified, a multidisciplinary team must be assembled to provide comprehensive care through all phases of treatment. The nursing staff is vital to this team because they are often the individuals who coordinate services involved in the care of the child with a posterior fossa tumor. This case study illustrates the phases of diagnosis and treatment of a child with a medulloblastoma and highlights critical care nursing challenges. Following the case study presentation, a summary describes posterior fossa tumors including epidemiology, pathophysiology, clinical manifestations, and outcome. The case study is integrated throughout this review to highlight key issues for critical care nurses to explore.

Cerebellar Neoplasms↗

Analysis of the structure of HIV-1 protease complexed with a hexapeptide inhibitor. Part II: Molecular dynamic studies of the active site region.

Six models of the catalytic site of HIV-1 protease complexed with a reduced peptide inhibitor, MVT-101, were investigated. These studies focused on the details of protonation of the active site, its total net charge and hydrogen bonding pattern, which was consistent with both the observed coplanar configuration of the acidic groups of the catalytic aspartates (Asp-25 and Asp-125) and the observed binding mode of the inhibitor. Molecular dynamic simulations using AMBER 4.0 indicated that the active site should be neutral. The planarity of the aspartate dyad may be due to the formation of two hydrogen bonds: one between the inner O delta 1 oxygen atoms of the two catalytic aspartates and another between the O delta 2 atom of Asp-125 and the nitrogen atom of the reduced peptide bond of the bound inhibitor. This would require two additional protonations, either of both aspartates, or of one Asp and the amido nitrogen atom of Nle-204. Our results favor the Asp-inhibitor protonation but the other one is not excluded. Implications of these findings for the mechanism of enzymatic catalysis are discussed. Dynamic properties of the hydrogen bond network in the active site and an analysis of the interaction energy between the inhibitor and the protease are presented.

Binding Sites↗

Acute management of severe childhood asthma.

Severe childhood asthma is a serious, life-threatening disease that presents a challenge for patients, families, and caregivers. Despite evolving medical and pharmacologic therapies, the incidence and severity of asthma are increasing. Vasoactive substances are released in response to environmental and intrinsic triggers and result in bronchospasm, bronchial mucosal edema, and mucus plugging of the airways. Early recognition of symptoms and prompt, aggressive treatment, including oxygen, beta agonists, corticosteroids, and anticholinergic agents, are essential in halting the progression of asthma symptoms. In the most severe cases, intubation, mechanical ventilation, and treatment with anesthetic agents may be needed to avoid significant morbidity and mortality. This article reviews epidemiology, pathophysiology, and acute care of the child experiencing an acute asthma exacerbation.

Acute Disease↗

Antioxidant effects of tocotrienols in patients with hyperlipidemia and carotid stenosis.

Antioxidants may have a role in the prevention of atherosclerosis. In the present trial, we investigated the antioxidant properties of Palm Vitee, a gamma-tocotrienol-, and alpha-tocopherol enriched fraction of palm oil, in patients with carotid atherosclerosis. Serum lipids, fatty acid peroxides, platelet aggregation and carotid artery stenosis were measured over an 18-month period in fifty patients with cerebrovascular disease. Change in stenosis was measured with duplex ultrasonography. Ultrasound scans were done at six months, twelve months, and yearly thereafter. Bilateral duplex ultrasonography revealed apparent carotid atherosclerotic regression in seven and progression in two of the 25 tocotrienol patients, while none of the control group exhibited regression and ten of 25 showed progression (P < 0.002). Serum thiobarbituric acid reactive substances, an ex vivo indicator of maximal platelet peroxidation, decreased in the treatment group from 1.08 +/- 0.70 to 0.80 +/- 0.55 microM/L (P < 0.05) after 12 mon, and in the placebo group, they increased nonsignificantly from 0.99 +/- 0.80 to 1.26 +/- 0.54 microM/L. Both tocotrienol and placebo groups displayed significantly attenuated collagen-induced platelet aggregation responses (P < 0.05) as compared with entry values. Serum total cholesterol, low density lipoprotein cholesterol, and triglyceride values remained unchanged in both groups, as did the plasma high density lipoprotein cholesterol values. These findings suggest that antioxidants, such as tocotrienols, may influence the course of carotid atherosclerosis.

Adenosine Triphosphate↗

Effects of canola oil on serum lipids in humans.

Previous work in this laboratory had shown in a pilot study that canola oil could lower blood pressure and serum cholesterol levels. Attempting to extend this work to a larger cohort over a longer period, a 4-month study using a 30 ml/day addendum of canola oil as the replacement of the edible oils in the usual diet was undertaken in 36 hypercholesterolemic and/or hypertriglyceridemic subjects. Serum low-density-lipoprotein cholesterol (LDL-C) decreased from 173 +/- 9.0 to 160 +/- 10.0 mg/dl, p less than 0.025. Blood pressure, total cholesterol, and high-density-lipoprotein cholesterol (HDL-C) did not change significantly even though the HDL subfractions did, HDL2 decreasing and HDL3 increasing.

Adult↗

Dynamic properties of the first enzymatic reaction steps of porcine pancreatic elastase. How rigid is the active site of the native enzyme? Molecular dynamics simulation.

Two molecular dynamics simulations (100 and 50 ps) of native porcine pancreatic elastase i.e., without bound substrate and with the active site hydrated by a dome of water (630 molecules) have been performed. Dynamical properties of the catalytic tetrad have been examined. While relative conformations of the Asp 102, His 57, and Ser 214 are rather stable in time, the side chain of Ser 195 undergoes several conformational changes. No preferences are observed for the formation of a hydrogen bond between the O gamma-H group (Ser 195) and nitrogen N, (His 57). A cluster of ordered water molecules effectively competes with the H-O gamma group (Ser 195) and thereby prevents the formation of this H bond, which is generally agreed to be crucial for catalysis.

Animals↗

Simulations of dynamical properties of a Michaelis complex: porcine pancreatic elastase and the hexapeptide, Thr-Pro-n Val-Leu-Tyr-Thr.

Molecular dynamic simulations (30ps) of the Michaelis complex of hexapeptide (Thr-Pro-nVal-Leu-Tyr-Thr) bound to porcine pancreatic elastase (PPE) hydrated by about 2000 water molecules have been performed using the AMBER 3.0 program package. Dynamical properties of the conformation of the active site have been examined. A comparison with previously reported simulations of native PPE shows that after the substrate is bound, the catalytically crucial H-bond between O gamma-H group of (Ser 195) and nitrogen N epsilon (His 57) is more readily formed. These results show, however, that the H-bond does not adopt the most favorable conformation. The O gamma-H group of Ser 195 has a statistical preference for an attractive interaction with the O = C carbonyl (Ser 214) rather than the nitrogen N epsilon (His 57).

Amino Acid Sequence↗

Obstructive sleep apnea syndrome: correction by mandibular advancement.

The obstructive sleep apnea syndrome (OSAS) is being recognized with increasing frequency in patients whose loud "heroic" snoring is coupled with significant and frequently debilitating daytime somnolence. Polysomnographic testing can clearly establish the diagnosis of this problem, but the etiology is multifactorial and the treatment options are varied. Although mandibular retrusion is not infrequently identified in patients with OSAS, the role of mandibular advancement surgery in the treatment of OSAS has not been defined. A nonobese 43-year-old white man with documented OSAS and mandibular retrusion had multidisciplinary treatment including surgical advancement of the mandible in conjunction with orthodontic treatment and prosthetic dental rehabilitation. No operation was done on the palate, nor was any other treatment provided for the OSAS. Resolution of the OSAS with dramatic improvement of the patient's snoring was achieved. This case illustrates the successful integration of corrective jaw surgery into the treatment plan for this type of patient.

Adult↗

Multisystem failure in a child with HUS.

HUS is a complex multisystem disease. Research has increased our understanding of etiologic factors, presenting symptoms, lab findings, and course of the disease and has had an impact on treatment plans. As children present to community hospitals with symptomatology of dehydration, more careful analysis of electrolytes, BUN, creatinine, and hematologic smears have supported earlier diagnosis and directly impacted the morbidity and mortality of HUS. Astute ongoing nursing assessment and care in the critical care unit are crucial to promoting a favorable outcome.

Child, Preschool↗

Respiratory atopy in Rio de Janeiro.

An epidemiologic study was conducted in Rio de Janeiro, Brazil, evaluating 1,410 patients with asthma and/or rhinitis. Allergy skin testing was performed in 1,219 patients (intradermal and/or Multi-Test Lincoln Diagnostics techniques). Thirteen different allergens were tested: house dust, Dermatophagoides farinae, grasses, Alternaria tenuis, Hormodendrum hordei, Penicillium mix, Aspergillus fumigatus, dogs, cats, feathers, fleas, cockroaches, and household insects. The most frequent positive immediate allergy skin tests were house dust (74.08%) and mites (62.43%).

Allergens↗

Animation: a useful tool for protein molecular dynamicists, applied to hydrogen bonds in the active site of elastase.

Massive amounts of coordinate data result from molecular dynamics calculations. The animation program MDKINO is a simple but powerful tool for previewing or reviewing the results. In recent simulations of elastase, we have examined hydrogen bonding patterns, conformational changes involving shifts in ring positions and rotations of amino acid side chains, electric fields in interatomic space, and electric forces acting on chosen nuclei. Animation is also useful for checking on the stability of calculations in progress. Simple programming techniques achieve acceptable levels of animation with readily available hardware (PS330 or PS390 display with a serial interface to a laboratory VAX). In about half an hour, it is possible to make and watch a color stereo "movie" of a selected subsystem of a simulation (up to 1,000 frames of about 100 atoms each).

Binding Sites↗

Cold-induced cholinergic urticaria--case report.

A 9-year-old child with cold-induced cholinergic urticaria was studied. When exposed to cold water or ambient cold air, the patient developed generalized urticaria. The lesions consisted of punctate wheals and surrounding erythema similar to that seen in cholinergic urticaria. The patient did not react to cutaneous challenge with an ice cube and a cold water immersion test was negative. Urticaria was not provoked by vigorous exercise sufficient to cause profuse sweating. The methacholine skin test was reactive. The patient was well controlled by combination therapy with hydroxyzine plus cyproheptadine.

Air↗

Allergic bronchopulmonary aspergillosis does exist in Brazil.

A case of allergic bronchopulmonary aspergillosis is presented. The patient had corticosteroid-dependent asthma, recurrent pulmonary infiltrates clearing with oral prednisone bursts, positive dual (immediate and late) skin test (prick and intradermal) reactivity to Aspergillus fumigatus, 11% blood eosinophilia, elevated total serum IgE, positive precipitating antibody against Aspergillus fumigatus, and elevated specific serum antibodies to Aspergillus fumigatus (positive IgE and IgG antibody indices, and elevated IgE levels by both RAST and FAST). To our knowledge this is the first immunologically documented case of allergic bronchopulmonary aspergillosis in Brazil. Future survey studies are required.

Adult↗

Influence of nitrendipine and verapamil on plasma levels, urinary excretion, and beta-blocking effect of metoprolol.

Following randomized allocation eight healthy volunteers were treated for 1 week each with metoprolol alone (100 mg twice daily), verapamil 80 mg three times a day plus metoprolol 100 mg twice daily, and with nitrendipine 20 mg twice daily. Plasma levels and urinary recovery of the beta-blocker, antipyrine clearance, and heart rate on exercise were measured. Verapamil and nitrendipine slightly prolonged elimination half-life of metoprolol. The urinary recovery of the parent beta-blocker and of its alpha-hydroxy metabolite was elevated by both calcium antagonists (verapamil and nitrendipine). Exercise tachycardia (150 beats/min without drugs) was inhibited more pronounced on the combination therapies than under metoprolol administration alone. Results of the present study indicate that calcium antagonists enhance inhibition of exercise tachycardia caused by metoprolol, possibly due to their binding to myocardial beta-adrenergic receptors which is known from the literature. As both calcium antagonists did not increase plasma levels of metoprolol, in the present study a kinetic interaction between the beta-blocker and the calcium channel blockers investigated does not appear to be responsible for the pharmacodynamic effects observed.

Adult↗

Calculations of the conformational properties of acyclonucleosides. Part I. Stable conformations of acyclovir.

Conformational properties of te antiherpes agent acyclovir (acycloguanosine, ACG) were calculated using molecular mechanics approximation. Eighty two different stable conformations have been determined. The large number of local minima of the total enery, and small differences between them, point to the marked flexibility of the acyclic chain. The barrier to rotation around N9-C1 bond was calculated and found to be asymmetric (the lower equals 17 kJ/mol, the higher 63 kJ/mol). An energetic preference for the compact from of ACG was demonstrated. A comparison of the calculated conformations with the crystallographic structures is presented.

Acyclovir↗