Actin-containing sera from patients with adult respiratory distress syndrome are toxic to sheep pulmonary endothelial cells.

Actin released from damaged cells after a variety of tissue injuries appears to be involved in multiple organ dysfunction syndrome. Under experimental conditions, when the quantity of actin present in plasma is made to exceed the protective capacity of the actin-scavenging mechanism, microembolism and pulmonary vascular angiopathy have been noted in rats. It remains to be determined whether this injury is a result of a direct toxic effect or occurs indirectly via platelet activation or fibrin interactions. We examined the effect of sera from patients with adult respiratory distress syndrome (ARDS), as well as G-actin added to normal serum, on the viability, morphology, and function of cultured sheep pulmonary artery endothelial cells (SPAEC). Both patient sera and normal sera to which actin was added were toxic in the cell culture model; this toxicity could be abrogated, at least partially, by preincubation with gelsolin, which is known to complex with actin. A significant portion of the toxicity of sera from patients with ARDS was sensitive to heat (56 degrees C), suggesting an important role of complement. Sera from patients with ARDS were shown to contain filaments of F-actin by immunoblot and rhodamine phalloidin staining after ultracentrifugation. Thus, saturation of the actin-scavenging system by addition of exogenous G-actin to plasma produces direct pulmonary endothelial cell injury. Furthermore, plasma from patients with ARDS secondary to bacterial pneumonia is toxic to SPAEC, and a small but significant contributory role of actin is apparent in these studies.

A randomized, prospective evaluation of noninvasive ventilation for acute respiratory failure.

We compared noninvasive positive-pressure ventilation (NPPV), using bilevel positive airway pressure, with usual medical care (UMC) in the therapy of patients with acute respiratory failure (ARF) in a prospective, randomized trial. Patients were subgrouped according to the disease leading to ARF (chronic obstructive pulmonary disease [COPD], a non-COPD-related pulmonary process, neuromuscular disease, and status postextubation), and were then randomized to NPPV or UMC. Thirty-two patients were evaluated in the NPPV group and 29 in the UMC group. The rate of endotracheal intubation (ETI) was significantly lower in the NPPV than in the UMC group (6.38 intubations versus 21.25 intubations per 100 ICU days, p = 0.002). Mortality rates in the intensive care unit (ICU) were similar for the two treatment groups (2.39 deaths versus 4.27 deaths per 100 ICU days, p = 0.21, NPPV versus UMC, respectively). Patients with hypoxemic ARF in the NPPV group had a significantly lower ETI rate than those in the UMC group (7.46 intubations versus 22.64 intubations per 100 ICU days, p = 0.026); a similar trend was noted for patients with hypercapnic ARF (5.41 intubations versus 18.52 intubations per 100 ICU days, p = 0.064, NPPV versus UMC, respectively). Patients with ARF in the non-COPD category had a lower rate of ETI with NPPV than with UMC (8.45 intubations versus 30.30 intubations per 100 ICU days, p = 0.01). Although the rate of ETI was lower among COPD patients receiving NPPV, this trend did not reach statistical significance (5.26 intubations versus 15.63 intubations per 100 ICU days, p = 0.12, NPPV versus UMC, respectively). In conclusion, NPPV with bilevel positive airway pressure reduces the rate of ETI in patients with ARF of various etiologies.

Growth hormone improves body mass recovery with refeeding after chronic undernutrition-induced muscle atrophy in aging male rats.

The effects of growth hormone (GH) administration and refeeding after chronic undernutrition (UN) were investigated in Fischer 344 male rats aging into senescence (24.5 mo of age) during UN initiated at 12.5 mo of age that produced muscle atrophy and a 50% decrease in body mass. Muscle mass, protein, myosin heavy-chain (MHC) composition and circulating testosterone levels were measured and compared to controls with free access to food. Within 9 wk, refeeding + GH restored body mass to control levels, whereas it was still decreased with refeeding alone. By 24.5 mo of age, refeeding alone restored body mass, while addition of GH resulted in overshoot. UN uniformly decreased mass of the gastrocnemius, extensor digitorum longus, soleus and diaphragm muscles to 50-60% of controls. Refeeding and refeeding + GH restored these losses with some overshoot of gastrocnemius muscle suggesting hypertrophy. UN more than doubled slow Type I MHC composition and approximately halved fast Type IIB and IIX MHC in the deep gastrocnemius muscle while it increased Type IIA MHC in the diaphragm. Refeeding and refeeding + GH reversed these shifts. MHC shifts in the extensor digitorum longus and soleus muscles were not statistically significant, whereas UN increased fast Type IIA MHC followed by decrease with refeeding + GH. UN decreased testosterone levels to nearly zero followed by restoration with refeeding and refeeding + GH. We conclude that the phenotype of mixed-MHC muscles such as the gastrocnemius and diaphragm are most affected by chronic UN, which is reversible with refeeding and refeeding + GH. These alterations were associated with changes in circulating testosterone, which may be a key regulatory element in these processes.

Growth hormone restores aged diaphragm myosin composition and performance after chronic undernutrition.

The effects of growth hormone (GH) on diaphragm muscle myosin heavy chain (MHC) composition and mechanical performance were investigated in Fischer 344 male rats aged to senescence (24.5 mo of age). Chronic undernutrition (UN), refeeding (RF), and RF+GH were compared with ad libitum feeding by using a model of UN that produced a 50% decrease in body weight over a 12-mo period. The effect of aging was assessed by comparing MHC composition of ad libitum-fed rats at 12 and 24.5 mo of age. At senescence, significant decreases in slow type I (-23%) and fast type IIA (-31%) MHC had occurred with aging. Conversely, UN over this aging period increased types I (32-73%) and IIA (22-23%) MHC and decreased fast types IIB (32-54%) and IIX (30-31%) MHC. RF and RF+GH reversed these shifts back toward control values. At senescence, maximal specific force, maximal velocity, and specific power capacity were not different across treatment groups. During repetitive isotonic contraction trials, the diaphragms of UN rats maintained power production over time (54% of initial power at 60 s), whereas the power production of diaphragms of ad libitum-fed rats fell to 0% (P < 0.05). In comparison with UN rats, the diaphragms of RF and RF+GH rats produced 23 (not significant) and 11% (P < 0.05) of initial power, respectively, suggesting that RF+GH treatment restored performance characteristics after UN. We conclude that RF+GH can reverse alterations in MHC composition and mechanical performance produced by chronic UN in the aged rat diaphragm.

Diaphragm myosin heavy chain composition shifts in aging chronically-undernourished Fischer 344 male rats.

The effects of chronic undernutrition (UN) on respiratory muscle were investigated during UN producing a 50% decrease in body weight over a prolonged period (45 weeks) in Fischer 344 male rats. This model focused on progressive, aging-related changes in myosin heavy chain (MHC) profile over time, in which the confounding effects of early development and late senescence were avoided. With aging toward late adulthood (68 weeks), MHC composition of control diaphragms was shifted, with decreased type I (slow) and IIA MHC, and increased type IIB and IIX (fast) MHC. UN produced a divergence of this profile, with an increase in type I and IIA MHC, and decreased type IIX MHC. UN diaphragms in vitro were more resistant to loss of active force with fatigue, during repetitive contractions. However, passive tension rose disproportionately during fatigue, suggesting increased fatigability. We conclude that the observed changes in diaphragm mechanical function are consistent with the UN-induced shifts in MHC composition; however, the elevated passive tension with fatigue suggests additional UN-induced changes in mechanical properties that are possibly detrimental to respiratory muscle function. The UN-dependent divergence in phenotype and mechanical properties may be amplified by aging-related shifts in muscle MHC composition over time, in the control group.

Cocaine balloon aspiration: successful removal with bronchoscopy.

Ingestion of balloons containing illicit substances along with the potential toxic sequelae associated with these ingestions have been described in the literature. This report describes the successful bronchoscopic retrieval of a cocaine balloon after aspiration. A 39-year-old man was witnessed swallowing several balloons that were thought to contain heroin. Shortly after ingestion, the patient became unconscious and required nasotracheal intubation. Before intubation, several balloons were removed from the oropharynx. Naloxone 4 mg was administered en route to the emergency department (ED). Following naloxone, the patient awoke and became agitated and combative. On arrival in the ED, midazolam, succinylcholine, and vecuronium were required to manage his combativeness. Vital signs were: heart rate, 130 beats/min; blood pressure, 128/86 mm Hg; respirations, 12 breaths/min; temperature, 96.5 degrees F. A balloon and balloon tip were removed during lavage. Whole bowel irrigation with a polyethylene glycol electrolyte solution was initiated. A right upper lobe infiltrate was identified on chest X-ray and aspiration of a balloon was suspected. At bronchoscopy, a small yellow, intact balloon visualized in the basilar segment of the right lower lobe was removed. Toxicologic analysis of the balloon contents found cocaine. The rest of the patient's hospital course was unremarkable and he was discharged 5 days after admission. This case brings to light the potential concerns, such as respiratory compromise, associated with aspiration of small balloons in the body stuffer. Additionally, the potential for the development of toxicity if the balloon ruptures and toxin absorption occurs through through the lungs should be considered. Emergency physicians and toxicologists should be aware of this significant complication of packet ingestion in the body packer or stuffer and be prepared to intervene early during the course of the patient's treatment.

Nutrition in end-stage pulmonary disease.

Advanced pulmonary disease is frequently associated with the clinical syndrome of progressive weight loss. Current investigation has focused on both the etiology and treatment of this wasting syndrome. Important observations have been made regarding this frequent clinical problem and these will be reviewed. Continued investigation of practical clinical approaches to this frequent clinical problem, based on sound scientific inquiry, are needed.

Long-term outcome of critically ill elderly patients requiring intensive care.

OBJECTIVE: To evaluate the long-term mortality and morbidity of critically ill elderly patients requiring intensive care. DESIGN: Prospective comparison of outcome of critically ill patients aged 75 years and older with patients aged 65 to 74 years. PATIENTS: Critically ill patients aged 65 years and older who required intensive care and who were recruited during a 3-month period. MAIN OUTCOME MEASURES: Duration of hospitalization, hospital charges, procedures used in the intensive care unit, mortality in the hospital and during the follow-up period, and quality of life of survivors during the follow-up period. RESULTS: Ninety-seven patients were included in the study; 54 were 75 years or older and 43 were aged 65 to 74 years. No significant difference was noted between the two groups for length of stay in the hospital, hospital charges, or mortality at 1 year. Severity of illness, as assessed by Acute Physiology and Chronic Health Evaluation score at the time of intensive care unit admission, was a better predictor of survival than age. Quality of life, as assessed by activities of daily living, perceived quality of life, and Center for Epidemiologic Studies-Depression score, were not significantly different in either group at 1, 6, and 12 months after discharge from the hospital. Most patients in both groups described their quality of life as adequate and were willing to receive intensive care again, if necessary. CONCLUSION: Age alone is not an adequate predictor of long-term survival and quality of life in critically ill elderly patients.