Molecular dynamics study of surface-tethered S(CH2CH2O)6CH3: helix formation and thermal disorder.

We present the results of a molecular dynamics study of a set of surface-tethered S(CH2CH2O)6CH3 chains. In this study, we analyze helix formation, in addition to thermal disorder, and find that spontaneous helix formation and details of helix morphology depend on charge partitioning ascribed to oxygen and the methylene groups. The effects of varying surface coverage as well as chain-surface interaction strength indicate that a set of approximately 7/2 helical structures oriented predominantly normal to the surface are formed at near full coverage. This occurs even though thermal disorder clearly precludes a description based on the concept of a perfect crystalline monolayer. Thermal fluctuations in chain morphology in the vicinity of the terminal methyl groups lead to the exposure of oxygen to the external environment. We also find that the persistence of compact helix-containing domains at partial surface coverage results in the formation of well-defined cavities or void regions that expose the bare surface, even in the presence of strong chain-surface attractive interactions.

Hydration for a series of hydrocarbons.

The hydrophobic hydration in a series of hydrocarbons is probed by using molecular dynamics simulations. The solutes considered range from methane to octane. Examination of the shapes of the hydration shell suggests that there is no single stable structure surrounding these solutes. The structure of the water molecules around the solute is not significantly perturbed, even for octane, and the hydrogen bond network is essentially preserved. The solutes are accommodated in the voids of the tetrahedral network of water in such a way as to leave the local environment almost intact. The hydrophobic hydration arises primarily because of the plasticity of the hydrogen bond network. Even for octane we find very little evidence for water-mediated interactions between nonbonded carbon atoms, leading us to suggest that the transition to globular conformations can only occur for very long, linear hydrocarbon chains.

Acid-base disturbances in acute asthma.

The clinical features, arterial blood gases, and acid-base profile were examined in 229 consecutive episodes of acute asthma in 170 patients who required hospitalization. A simple respiratory alkalosis was the most common acid-base disturbance, occurring in 48 percent of the episodes. Metabolic acidosis, either alone or as part of a mixed disturbance, was noted in 28 percent. Of 60 episodes presenting with respiratory acidosis, 37 (62 percent) had a coexistent metabolic acidosis. Metabolic acidosis was more likely to occur in male subjects and in patients with evidence of more severe airflow obstruction. Patients with metabolic acidosis had an average anion gap of 15.8 mEq/L; these patients were more hypoxemic than those without metabolic acidosis and there was a significant inverse correlation between the anion gap and the degree of hypoxemia. We conclude that metabolic acidosis is a common finding in acute, severe asthma and suggest that the pathogenesis of lactic acidosis is multifactorial and includes contributions from lactate production by respiratory muscles, tissue hypoxia, and intracellular alkalosis.

Clinical features and outcome in patients with acute asthma presenting with hypercapnia.

To determine the clinical features and outcome of patients with hypercapnia from acute asthma, we examined 229 (62 men, 167 women) consecutive episodes of acute asthma over a 6-yr period. Sixty-one episodes were associated with hypercapnia at presentation (PaCO2 greater than 38 mm Hg). Men more commonly presented with hypercapnia: 31 of 62 (50%) men with acute asthma had hypercapnia compared with only 30 of 167 (18%) women (p less than 0.001). Patients with hypercapnia had a longer duration of chronic asthma and were more likely to be steroid-dependent. Hypercapnic patients had greater airway obstruction, respiratory rate, and pulsus paradoxus than did nonhypercapnic patients. Findings of a quiet chest on auscultation, inability to talk, and cyanosis also suggested the presence of hypercapnia. Five hypercapnic patients required mechanical ventilation, but hypercapnia did not prolong hospitalization. In nonventilated patients, hypercapnia resolved in a mean time of 5.9 h; 50% of hypercapnic episodes resolved by 4 h, and all resolved by 16 h. No patient presenting with normocapnia progressed to hypercapnia with therapy, and there were no deaths in either the hypercapnic group or the nonhypercapnic group. In patients with more than one admission, the PaCO2 of one episode correlated with the PaCO2 on a subsequent admission, suggesting a role for individual variation in ventilatory control. With appropriate medical therapy, most patients with hypercapnia from acute asthma have rapid reversibility, and mechanical ventilation usually can be avoided. However, these patients require close inhospital observation until it is certain that the acute asthmatic episode has resolved.

High-altitude medical problems.

A spectrum of medical problems, including self-limited acute mountain sickness, high-altitude retinopathy, and the potentially fatal high-altitude pulmonary and cerebral edemas, may afflict residents and sojourners at higher elevations. However, appropriate prevention and prompt recognition will minimize the impact of these disorders. Prevention is predicated upon slow ascent to altitude and minimizing initial exertion at altitude; in selected cases, preventive drug therapy with Diamox (Lederle, Pearl River, New York) is helpful. Early recognition and descent to lower altitude remain the cornerstones of therapy.

Molecular dynamics simulation study of a two-dimensional fluid mixture system: a model for biological membranes.

The computer simulation technique of molecular dynamics was applied to a model two-dimensional fluid mixture system to examine the short-range ordering of lipid and protein molecules in biological membranes. The model system consists of small disks (lipids) and large disks (proteins) with a radius ratio of 6, constrained to move in a plane. The particles interact with pairwise additive repulsive short range potentials, so as to simulate hard disks. Periodic boundary conditions are assumed in order to minimize boundary effects. For values of the number density of the small disks and of the temperature appropriate for a lipid membrane, the fraction, f, of small disks 'next to' at least one large disk was computed by molecular dynamics. This was done as a function of concentration and for several definitions of 'next to'. The molecular dynamics results show that, at moderately low mole fractions of the large disks, the calculated values of f deviate noticeably from the linear relation which would be expected in the absence of protein-protein proximity effects. The results are discussed in terms of current models of lipid-protein ordering in biological membranes.

Oral theophylline intoxication. A serious error of patient and physician understanding.

Twenty-two episodes of hospitalization for patients with inadvertent oral theophylline intoxication were reviewed to determine the mechanism of toxicity as well as clinical features and pharmacokinetic values. Toxic effects occurred in older subjects with poorly reversible airflow obstruction and evidence of reduced theophylline clearance. Maximum serum theophylline levels ranged from 22.4 to 104.8 mg/L. Gastrointestinal tract disturbances were the most common toxic effects; three patients had grand mal seizures. Serum theophylline levels were a poor predictor of serious toxic effects. Causes of theophylline intoxication included excessive drug ingestion by the patient, excessive dose prescription by the physician, and unrecognized drug interactions. With appropriate patient selection and education, as well as better understanding of theophylline kinetics and potential drug interactions, inadvertent oral theophylline intoxication can be minimized.

Cardiopulmonary resuscitation by medical and surgical house-officers.

In teaching hospitals the responsibility for cardiopulmonary resuscitation usually rests with the house-staff, yet most house-officers receive no formal training in life support. The life-support skills of 45 medical and surgical house-officers in a university teaching hospital were tested by means of simulated cardiac arrests. House-officers were graded on the basis of a performance checklist derived from the standards of the American Heart Association. No house-officer received a pass score in basic life support (BLS). Only 29% could properly compress and ventilate the mannequin. In advanced cardiac life support (ACLS) only one-third could intubate in 35 s or less; only 31%, 40%, and 33% could manage ventricular fibrillation, asystole, and complete heart block, respectively. Some house-officers were unable to operate the defibrillator or assemble resuscitation equipment. Many house-officers displayed helplessness and anxiety during the simulations; fourteen (40%) were prompted to register for additional advanced life-support courses. The performance of medical and surgical house-officers was equal. House-officers who had received prior life-support training performed better in BLS (p less than 0.001) but not in ACLS. It was concluded that (a) most medical and surgical house-officers are not reasonably proficient in BLS and ACLS, and (b) cardiac arrest simulation is a motivating exercise which permits analysis of each house-officer's life-support skills. House-officers should have more training and practice in life support, or they should not have primary responsibility for cardiopulmonary resuscitations.