Correlation of flunisolide plasma levels to eosinopenic response in humans

Plasma levels of flunisolide were measured in healthy male volunteers after the administration of single doses of the drug by the intravenous, oral, intranasal, and bronchial inhalation routes. The systemic availability of a 1-mg dose orally was only 21%. After a single dose of approximately 0.117 mg intranasally plasma levels ranged up to 1 ng/ml. When 1 mg was administered by bronchial inhalation, peak or near peak plasma levels were recorded at 2 min and remained near this level throughout the first hour before declining at a rate similar to that observed after flunisolide intravenously (plasma ). Gargling with an alcoholic mouthwash immediately after inhalation reduced plasma levels at 30 and 60 min but not earlier, suggesting rate-limiting dissolution of flunisolide in bronchial fluids or rate-limiting diffusion across the mucociliary blanket or pulmonary membrane. The systemic availabilities of the inhaled-mouthwash and inhaled-no mouthwash doses were 32% and 39%, respectively. Systemic potency of flunisolide, measured by eosinopenic response, was oral < inhaled < intravenous and correlated with the systemic availability of flunisolide after drug administration by these three routes. These pharmacokinetic properties of flunisolide are clinically advantageous in that relatively small doses are delivered topically to the target organs, i.e., the nasal mucosa and lungs, whereas a large portion of the dose is swallowed and subsequently extensively metabolized to relatively inactive metabolites.     

Evidence that hemodialysis does not improve the glucose tolerance of patients with chronic renal failure

Oral glucose tolerance tests were performed in 16 patients with chronic renal failure undergoing hemodialysis. In ten patients, studies were performed before and after one dialysis, while six patients were studied immediately prior to the start of chronic hemodialysis and just after the fifteenth dialysis. Hemodialysis did not lead to improvement in either the plasma glucose or growth hormone response to the oral glucose challenge. There was, however, a modest increase noted in the plasma insulin level 2 hr after the oral glucose challenge following dialysis. On the other hand, there was not any change in the overall relationship between the plasma glucose and insulin response to the oral glucose load as a result of dialysis. These results indicate that chronic hemodialysis as it is routinely conducted in the treatment of patients with chronic renal failure has, at best, a relatively modest effect on the plasma glucose, growth hormone, and insulin responses to an oral glucose challenge.     

Reappraisal of the role of insulin in hypertriglyceridemia

We have previously proposed a sequential hypothesis to help explain the genesis of endogenous hypertriglyceridemia in man. This scheme states that insulin resistance → hyperinsulinemia → increased very low density lipoprotein (VLDL)-triglyceride (TG) production rate → increased plasma TG levels. In this study we have measured each of these metabolic variables in 34 nonobese subjects all consuming the same isocaloric diet. We have found highly significant positive correlations between insulin resistance and insulin response (r = 0.74, p < 0.0001), between insulin response and VLDL-TG production rate (r = 0.72, p < 0.0001), and between VLDL-TG production rate and plasma TG level (r = 0.88, p < 0.0001). Furthermore, these relationships were found to be independent of any possible effect of obesity. Thus, highly positive correlations were found for each step of the scheme, and we believe the over-all hypothesis is greatly strengthened. Additionally, the cross correlation between plasma TG levels and insulin response was also highly significant (r = 0.73, p < 0.0001). On the other hand, glucose response did not correlate with any measure of TG metabolism. On the basis of these results we conclude that insulin plays an important role in the genesis of endogenous hypertriglyceridemia through its influence on VLDL-TG production.     

Disassociation of the plasma insulin response from the blood glucose concentration during glucose infusions in normal dogs

Twenty-two anesthetized dogs were given a constant glucose infusion (14 mg/kg/min) for 360 min, while blood glucose concentration was continuously monitored. Plasma insulin concentration was measured every 30 min. The blood glucose peaked at 60 min and then steadily fell (mean fall, $\text{56}\text{mg}\text{100}\text{ml}$), while plasma insulin continuously rose (mean rise, 65 μU/ml). This suggests that blood glucose concentratiion was not the primary stimulus for insulin secretion. In a second series of experiments, five dogs received glucose infusions as described above. One week later, each dog was reinfused with a larger total glucose load, regulated by continuous blood glucose monitoring to exactly reproduce the blood glucose response observed during the first infusion. Plasma insulin concentrations during the high load infusions were significantly higher than during the low load infusions. Thus, changes in glucose load produced changes in plasma insulin concentration, even though blood glucose levels were held constant. Thus, using two different approaches, we have demonstrated that plasma insulin levels can be dissociated from the coexisting blood glucose concentration. These results suggest that the level of blood glucose may not be the primary determinant of the insulin response to glucose during the chronic phase of insulin secretion.     

Using a Natural Language Processing and Machine Learning Algorithm Program to Analyze Inter-Radiologist Report Style Variation and Compare Variation Between Radiologists When Using Highly Structured Versus More Free Text Reporting

PurposeTo use a natural language processing and machine learning algorithm to evaluate inter-radiologist report variation and compare variation between radiologists using highly structured versus more free text reporting.Materials and Methods28,615 radiology reports were analyzed for 4 metrics: verbosity, observational terms only, unwarranted negative findings, and repeated language in different sections. Radiology reports for two imaging examinations were analyzed and compared – one which was more templated (ultrasound – appendicitis) and one which relied on more free text (chest radiograph – single view). For each metric, the mean and standard deviation for defined outlier results for all dictations (individual and group mean) was calculated. The mean number of outlier metrics per reader per study was calculated and compared between radiologists and between the two report types. Wilcoxon rank test and paired Wilcoxon signed rank test were applied. The radiologists were also ranked based on the number of outlier metrics identified per study.ResultsThere was great variability in radiologist dictation styles – outlier metrics per report varied greatly between radiologists with the maximum 10 times higher than the minimum score. Metric values were greater (P < 0.0001) on the standardized reports using free text than the more structured reports.ConclusionsThe algorithm successfully evaluated metrics showing variability in reporting profiles particularly when there is free text. This variability can be an obstacle to providing effective communication and reliability of care.     

Exercise training soon after myocardial infarction

To assess the cardiovascular effects of exercise training soon after clinically uncomplicated myocardial infarction, 70 men (mean age 54 years) underwent gymnasium training (no. = 28), home training (no. = 12) or no training (no. = 30) 3 to 11 weeks after the acute event. During this 8 week interval functional capacity increased significantly (P < 0.001) in all three groups: gymnasium training, 66 percent; home training, 41 percent; and no training, 34 percent. Peak functional capacity at 11 weeks was 11.0 ± 1.6, 10.3 ± 1.4 and 9.4 ± 1.8 (mean ± standard deviation) multiples of resting energy expenditure (METs) in the three groups—values approximating those of sedentary men of similar age without coronary heart disease. Functional capacity increased more in the gymnasium training group than in the no training group, but this difference was statistically significant only in patients without exercise-induced ischemie S-T segment depression or angina pectoris (P < 0.01). Another “training effect”—diminished heart rate response to submaximal work—was also observed in all three groups. It is concluded that (1) symptom-limited treadmill exercise testing performed soon after clinically uncomplicated myocardial infarction is feasible and safe and provides useful guidelines for physical reconditioning. (2) Patients who demonstrate nonischemic responses to treadmill exercise testing soon after infarction may safely undergo unsupervised exercise training at home. (3) Formal exercise training may not be required to restore functional capacity to nearly normal values soon after clinically uncomplicated myocardial infarction.     

Traumatic pulmonary artery--left atrial fistula: an unusual case of cyanosis in an adult.

Eighteen months after sustaining a stab wound to the left upper chest, a 59-year-old man presented with cyanosis and extertional dyspnea. Arterial desaturation due to a central 22 per cent right-to-left shunt was present. A selective pulmonary arteriogram demonstrated a fistula between the main pulmonary artery and the left atrium. At operation the fistula was closed. A laceration of the pulmonic valve and healed pericarditis were present. Marked symptomatic improvement followed the operation, but a murmur of pulmonic valvular regurgitation persisted. The fistula and laceration of the pulmonic valve were probably traumatic in origin.