Cycling of inspiratory and expiratory muscle groups with the ventilator in airflow limitation.

Research on patient-ventilator interactions has largely focused on inspiratory events, with little attention paid to expiration. We sought to determine the importance of the timing and magnitude of expiratory muscle activity in causing patient-ventilator dyssynchrony. Our study was done with healthy subjects receiving pressure support in whom we induced airflow limitation with a Starling resistor.

Does resistive loading decrease diaphragmatic contractility before task failure?

While sustaining a load that leads to task failure, it is unclear whether diaphragmatic fatigue develops progressively or occurs only at task failure. We hypothesized that incremental loading produces a progressive decrease in diaphragmatic contractility ever before task failure. Ten subjects generated 60% of maximal transdiaphragmatic pressure (Pdimax) for 2 min, 4 min, and until task failure.

Respiratory muscle dysfunction in mechanically-ventilated patients.

The interaction between a patient and a ventilator is the major determinant of the amount of respiratory muscle rest achieved by the machine. We are beginning to acquire a better understanding of the mechanisms that underlie this complex interaction, but this information has yet to be integrated into the routine clinical management of ventilator-supported patients. To achieve that goal, we need better techniques of detecting and monitoring patient-ventilation asynchrony, and the development of simple algorithms that can minimize its occurrence.

Effect of hyperoxic hypercapnia on variational activity of breathing.

Dysrhythmias of breathing occur in several clinical disorders, but their mechanistic basis is obscure. To understand their pathophysiology, factors responsible for the variability of breathing need to be defined. We studied the effect of hyperoxic hypercapnia (CO2) on the variational activity of breathing in 14 volunteers before and after delivering CO2 nonobstrusively via a plastic hood.

Comparison of assisted ventilator modes on triggering, patient effort, and dyspnea.

In 11 ventilator-dependent patients, we undertook a head-to-head comparison of patient-ventilator interaction during four ventilator modes: assist-control ventilation (ACV), intermittent mandatory ventilation (IMV), pressure support (PS), and a combination of IMV and PS. Progressive increases in IMV rate and PS level each decreased inspiratory pressure-time product (PTP) (p < 0.0001).

The effect of acute ethanol (EtOH) exposure on protein kinase C (PKC) activity in anterior pituitary.

Alterations in the protein kinase C (PKC) pathway may interrupt anterior pituitary luteinizing hormone (LH) synthesis and/or secretion, which may impair normal reproductive function. Work by our laboratory and others has shown that EtOH has profound deleterious effects on the regulation of the hypothalamic-pituitary-gonadal (HPG) axis. The present study focuses on PKC translocation from the cytosol to the membrane of anterior pituitary after acute EtOH exposure.

Effect of elastic loading on variational activity of breathing.

To examine the effect of elastic loading on variational activity of breathing, we studied 11 healthy subjects breathing at rest and with inspiratory elastic loads of 9 and 18 cm H2O/L, applied randomly for 1 h each. Compared with rest, a load of 18 cm H2O/L decreased gross variability, quantitated as standard deviation, of tidal volume (VT) and expiratory time (TE) (p < 0.01 in both instances) but increased that of inspiratory time (TI) (p < 0.

Relationship between transdiaphragmatic and mouth twitch pressures at functional residual capacity.

The clinical application of transdiaphragmatic twitch pressure (Pdi,tw) response to phrenic nerve stimulation has been hindered by the requirement for placement of oesophageal and gastric balloons. Investigators have reported that mouth twitch pressure (Pmo,tw) estimates Pdi,tw accurately at lung volumes above and below functional residual capacity (FRC). However, it is not known whether Pmo,tw estimates Pdi,tw accurately when stimulation is performed at FRC during relaxed conditions.

Lansoprazole heals erosive reflux oesophagitis in patients with Barrett's oesophagus.

Background: Barrett's oesophagus is thought to be a complication of severe gastro-oesophageal reflux.

Aim: To determine whether the proton pump inhibitor, lansoprazole, is effective in healing erosive reflux oesophagitis in patients with Barrett's oesophagus.

Methods: An 8-week, randomized, double-blind study was conducted using patients with both erosive reflux oesophagitis and Barrett's oesophagus.

Serum albuterol levels in mechanically ventilated patients and healthy subjects after metered-dose inhaler administration.

In mechanically ventilated patients, systemic blood levels of inhaled drugs reflect absorption from the lower respiratory tract alone since, unlike nonintubated patients, oropharyngeal and gastrointestinal absorption cannot occur. To determine the efficiency of aerosol administration by a metered-dose inhaler (MDI), we measured serum albuterol levels after administration by a MDI and spacer to nine mechanically ventilated patients (10 puffs) and to 10 healthy subjects (six puffs). Serum albuterol levels (+/- SEM) quantitated by high-performance liquid chromatography and electrochemical detection were: 0.

Sustained effects of a single injection of ethanol on the hypothalamic-pituitary-gonadal axis in the male rat.

The hormones responsible for regulating the hypothalamic-pituitary-gonadal axis are essential for proper reproductive function. Ethanol (EtOH) has been shown to exert its effect at all three levels of this axis. The present study defines striking differences in the time course of recovery of luteinizing hormone (LH) in gonadally intact, compared with, castrated male rats after acute EtOH administration.

Dose-response to bronchodilator delivered by metered-dose inhaler in ventilator-supported patients.

In nonintubated patients, metered-dose inhalers (MDIs) are accepted as the most convenient, efficient, and cost effective method of administering inhaled bronchodilators. Recent studies have demonstrated the efficacy of MDIs in ventilator-supported patients; however, the optimal dose of a bronchodilator from a MDI is unknown. We determined the response to increasing doses of albuterol administered by a MDI and cylindrical spacer to 12 mechanically ventilated patients with chronic obstructive pulmonary disease (COPD).

Aerosol delivery from a metered-dose inhaler during mechanical ventilation. An in vitro model.

Successful bronchodilator therapy with a metered-dose inhaler (MDI) in intubated, mechanically ventilated patients requires adequate delivery of aerosol to the lower respiratory tract. We determined the effect of ventilator mode, inspiratory flow pattern, humidity, and spontaneous respiratory effort on albuterol delivery in a model of the trachea and bronchi. The model was ventilated through an endotracheal tube during controlled mechanical ventilation (CMV), assist control (AC), pressure support (PS), and continuous positive airway pressure (CPAP), separately with a dry and humidified ventilator circuit.

The effect of castration on steady state levels of luteinizing hormone-releasing hormone (LHRH) mRNA and proLHRH processing: time course study utilizing semi-quantitative reverse transcription/polymerase chain reaction.

Many studies have consistently shown that castration induces a prompt increase in serum levels and pituitary content of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as a concomitant rise in steady state levels of the messenger RNAs directing their synthesis. The reports of effects of castration on the overall physiology of hypothalamic luteinizing hormone-releasing hormone (LHRH)--steady state levels of LHRH mRNA, post-translational processing and secretion--have, however, not been consistent. The goal of the studies reported here was to provide the first analysis of the effect of castration, at multiple postoperative time points, on steady state levels of LHRH mRNA and on the levels of hypothalamic proLHRH.

Variability of patient-ventilator interaction with pressure support ventilation in patients with chronic obstructive pulmonary disease.

In 12 patients with chronic obstructive pulmonary disease (COPD) receiving pressure support ventilation (PSV), we studied the variability of respiratory muscle unloading and defined its physiologic determinants using a modified pressure-time product (PTP). Inspiratory PTP/min decreased as PSV was increased (p < 0.001), but there was considerable interindividual variation: coefficients of variations of up to 96%.

Evolution of mouse hepatitis virus (MHV) during chronic infection: quasispecies nature of the persisting MHV RNA.

Coronavirus infection of mice has been used extensively as a model for the study of acute encephalitis and chronic demyelination. To examine the evolution of coronavirus RNA during chronic demyelinating infection, we isolated RNA from intracerebrally inoculated mice at 4, 6, 8, 13, 20, and 42 days postinfection and used reverse transcription-polymerase chain reaction amplification methods (RT-PCR) to detect viral sequences. RNA sequences from two viral structural genes, the spike gene and the nucleocapsid gene, were detected throughout the chronic infection.

Osteoid osteoma of the upper extremity.

Osteoid osteomas, relatively rare lesions in the upper extremity, can be a persistent source of hand or wrist pain. Patients under age 40 who have otherwise unexplained pain should be evaluated. Relief of pain with oral nonsteroidal anti-inflammatory drugs should suggest the possibility of osteoid osteoma.

Anti-lipid A monoclonal antibodies and anti-LPS antiserum effects on limulus activity of LPS.

Anti-lipid A monoclonal antibodies (A78S1 and A523) and anti-LPS antiserum can decrease the mortality due to endotoxic shock in the newborn rat. However, in vitro LPS detoxification of anti-lipid A monoclonal antibodies is not known. Thus, we studied in vivo effects of A78S1 (IgG), A523 (IgM), and anti-LPS antiserum on Limulus activity.

Pathophysiology of failure to wean from mechanical ventilation.

Weaning patients from mechanical ventilation constitutes a major portion of the workload in an intensive care unit, as over 40% of total ventilator time is consumed by the weaning process. Several pathophysiological mechanisms may be responsible for weaning failure, but the precise role of each is incompletely understood. Patients who fail a weaning trial commonly develop hypercapnia, which appears to be due to decreased tidal volume rather than a primary decrease in respiratory drive.

Decreased gluconeogenesis and increased glucose disposal without hyperinsulinemia in 10-day-old rats with endotoxic shock.

Glucose dyshomeostasis is a common and life-threatening sign of endotoxic shock in the newborn. In this study, liver gluconeogenesis was evaluated in 10-day-old rats with endotoxic shock using the isolated perfused liver. Phosphoenolpyruvate carboxykinase (PEPCK) activity and PEPCK mRNA abundance were measured to confirm altered gluconeogenesis.

Nutritional aspects of HIV infection.

Wasting may not be an inevitable consequence of HIV infection but may be a consequence of multiple nutritional insults that are additive without periods of replenishment in between. Protein energy malnutrition in AIDS patients may be consequential to underlying illness and concomitant to death as a result of that illness or may hasten a patient's demise, that is, starvation with fatal loss of body cell mass. Mortality is closely related to weight loss.

Management of intra-articular fractures of the metacarpophalangeal joint.

Displaced intra-articular fractures of the metacarpal head and of the proximal articular surface of the proximal phalanx often require open reduction and internal fixation, particularly if an articular step off is present. If secure internal fixation can be achieved, early motion may be instituted. Diagnosis may be facilitated by special views and tomography.

Refinements using free-tissue transfer for complex cranial base reconstruction.

Resection of skull base tumors may sometimes result in massive extirpation defects that are not amenable to local tissue closure. Closure of large basicranial defects can be performed with either a myocutaneous, a deepithelialized myocutaneous, or a simple muscle free flap designed from the ample rectus abdominis vascular territory. This free-tissue donor site has abundant and reliable well-vascularized tissue that can easily be customized to seal these tenuous areas.

The antinuclear antibody test. When is a positive result clinically relevant?

The antinuclear antibody (ANA) test is sensitive but not specific. Many nonrheumatic diseases and conditions can cause positive results, and some healthy persons have positive results. ANA testing should not be used to evaluate patients who have vague complaints or symptoms.

Entrapment neuropathies. A guide to avoiding misdiagnoses.

Nerve entrapment has many possible causes and can mimic a broad range of disorders. A carefully taken history and thorough neurologic examination are the most important parts of evaluation, and plain radiography, electromyography, and nerve conduction velocity studies are useful adjuncts. Treatment options include correction of underlying causes; reduction in activity; exercise programs; wearing of splints, arch supports, or foot braces; local injections of corticosteroids and/or anesthetics; use of nonsteroidal anti-inflammatory drugs; and surgical decompression.