Effects of prednisolone on the differentiation of mouse lung adenomas in culture.

Explants of pulmonary adenomas, induced in mice by urethan, were cultured with or without prednisolone for 72 hr. After this time, the cuboidal epithelial cells of the tumor contained many more lamellar bodies than the nonsteroid control cultures. Incorporation of labeled palmitic acid into saturated phosphatidylcholine was not significantly increased in these short-term steroid-treated cultures. The results indicate that steroid enhances the maturation of cultured pulmonary adenoma cells into cells morphologically indistinguishable from type II alveolar epithelial cells of normal lung.

Performance of "standardized examinees" in a standardized-patient examination of clinical skills.

PURPOSE: As a first step in testing the utility of using trained "standardized examinees" (SEs) as a quality-assurance measure for the scoring process in a standardized-patient (SP) examination, to test whether medical residents could simulate students in an SP examination and perform consistently to specified levels under test conditions. METHOD: Fourth-year students from the Baltimore-Washington Consortium for SPs participated in a National Board of Medical Examiners Prototype Examination of clinical skills consisting of twelve 15-minute student-patient encounters in 1994-95. For this examination, internal medicine residents were trained to act as ordinary candidates and to achieve target scores by performing to a set level on specific checklist items used by SPs for recording interviewing, physical-examination, and communication skills. The "strong SEs" were trained to score 80% correct on six of the examination's 12 cases (study cases), and the "weak SEs" were trained to score 40% correct on the same six cases. The strong and weak SEs' checklist scores on the study cases were compared through independent, two-tailed t-tests. When there was less than 85% agreement on specific checklist items in each case between the SE training and the SP recording, videotapes of the cases were reviewed; in such cases an SE's performance was the final score agreed upon after review. RESULTS: Seven SEs took the SP examination and were not detected by the SPs. There was a total of 84 discrepancies between predicted and recorded checklist scores across 659 checklist items in 40 encounters scored by the SPs. After correcting the discrepancies based on videotape review, the estimated actual mean score was 77.3% for the strong SEs and 44.0% for the weak SEs, and was higher for the strong SEs in each study case. The overall fidelity of the SEs to their training was estimated to be 97%, and the overall SP accuracy was estimated to be 91%. The videotape review revealed 47 training-scoring discrepancies, most in the area of communication skills. CONCLUSION: This study suggests that SEs can be trained to specific performance levels and may be an effective internal control for a high-stakes SP examination. They may also provide a mechanism for refining scoring checklists and for exploring the validity of SP examinations.

Cigarette smoke exposure in vivo increases cyclic GMP in rat lung.

The enzyme guanylate cyclase is stimulated to produce cycle guanosine 3',5'-monophosphate (GMP) when lung tissue is exposed to cigarette smoke in vitro. These experiments tested whether in vivo exposure in rats to cigarette smoke produces a similar response. Adult rats were anaesthetized with pentobarbital and ventilation with mixtures of air and cigarette smoke at 10 cm H2O inspiratory pressure was achieved after a tracheotomy was performed. Lung tissue samples were taken at intervals during 20 min exposure period and analyzed for levels of cyclic adenosine 3', 5'-monophosphate (AMP) and cycle GMP. Blood carboxyhemoglobin (COHb) levels at 5 min and 15 min of exposure showed high, but sublethal levels of COHb. lung tissue cAMP was unchanged with this exposure, but cGMP levels rose dramatically. Rat lungs showed no changes related to ventilation under similar conditions in the absence of smoke. This observed response of cGMP to cigarette smoke may represent an important pulmonary defense mechanism.

Lung tissue guanosine 3',5'-monophosphate: effects of ventilation and anesthesia.

In vivo levels of guanosine 3',5'-cyclic monophosphate (cGMP) in rat lung were measured by radioimmunoassay. The basal levels of this agent were found to change depending on the method of killing or anesthesia used. Lowest values were found after microwave irradiation to the head (10.2 fmol/mg wet wt). Values after pentobarbitol anesthesia, with or without atropine, were significantly higher (19-24 fmol/mg). In animals anesthetized with pentobarbital and ventilated at pressures of 7 cmH2O with no end-expiratory pressure, lung cGMP was 42-49 fmol/mg. Ventilation at higher pressures resulted in much higher levels of cGMP (20 cmH2O, 105 fmol/mg; 30 cmH2O, 233 fmol/mg). The response of cGMP to ventilation was not blocked by pretreatment of the animals with atropine. High-pressure ventilation was without effect on lung adenosine 3',5'-cyclic monophosphate.

Dibutyryl cyclic GMP and hyperventilation promote rat lung phospholipid release.

Ventilation of rats at high inspiratory pressures raises lung tissue content of guanosine 3',5'-cyclic monophosphate (cGMP). Hyperventilation in rabbits augments release of phospholipid into lavage fluid. Can cGMP, in the absence of hyperventilation, increase lung phospholipid release? Sprague-Dawley rats are injected with [14C]palmitate, and after 1.5 h are anesthetized and ventilated for 20 min. Three groups are ventilated at peak inspiratory pressures (PIP) of 10 cmH2O, while saline, dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP), or dibutyryl cGMP (DBcGMP) is infused into the pulmonary artery. In a fourth group, saline is infused into the pulmonary artery, but ventilation is performed with PIP of 25 cmH2O. Lung tissue and lavage fluid are then analyzed for phospholipid (PL) content and for incorporation of [14C]palmitate into lavage and tissue PL fractions. Ventilation at increased pressure and infusion of DBcGMP are associated with increases in release of labeled PL into lavage fraction. The findings suggest that the increase in lavage PL release associated with hyperventilation is, at least in part, mediated by cGMP.

Antiarrhythmic effects of cyclic guanosine 3' :5'-monophosphate and sodium nitroprusside on barium chloride arrhythmias in rabbits.

The hypothesis that c GMP and sodium nitroprusside (NP), an activator of guanylate cyclase which elevates levels of c GMP, have antiarrhythmic activity was tested in the barium chloride (BaCl2) model of arrhythmias. Electrocardiograms were recorded continuously on tape in unanesthetized New Zealand white rabbits weighing approximately 2.0 kg. BaCl2, 4 mg/kg i.v. bolus, induced frequent ventricular ectopic beats. These ventricular arrhythmias were abolished by 8-bromo-c GMP, 5 mg/kg, injected into the left ventricle (5/6 rabbits), NP 25.0 microgram/kg/min i.v. (6/6), NP 10 micrograms/kg/min i.v. (3/6), and markedly reduced in frequency by NP 10 micrograms/kg/min (3/6). In temporal association with NP, 4 fold increases in c GMP levels in blood and significant increases in myocardial GMP were found compared to control animals (n = 6). In this model, c GMP and NP have significant antiarrhythmic properties. NP effect may be mediated by alterations in c GMP metabolism.

Human lung lavage surfactant enhances staphylococcal phagocytosis by alveolar macrophages.

We tested the effect of a preparation of human lung lavage surfactant (SAM) on phagocytosis and intracellular killing of Staphylococcus aureus by human alveolar macrophages (AM). When staphylococci were incubated with 100 to 300 micrograms of SAM, AM phagocytosis but not intracellular killing efficiency was enhanced. The mean numbers of intracellular staphylococci/AM were 36.0 +/- 2.7 and 23.3 +/- 2.8 in the SAM and control groups, respectively (p less than 0.001). The AM intracellular killing efficiency was 40.9 +/- 3.3% and 39.5 +/- 3.9% in the SAM and control groups, respectively (p greater than 0.05). Our results suggest that SAM is an important nonimmune opsonin for bacterial phagocytosis by human AM.