Joel B. Karlinsky

Pulmonary mucormycosis in the setting of chronic obstructive pulmonary disease. A case report and review of the literature.

We describe the first case of pulmonary mucormycosis occurring in a patient with chronic obstructive pulmonary disease (COPD) maintained on chronic low dose oral steroids (10 mg/day). The diagnosis was made by direct histopathological examination and culturing of infected tissue obtained by fiberoptic bronchoscopy. Pulmonary mucormycosis is caused by infection with an opportunistic fungus of the order Mucorales and is an acute, rapidly developing and often fulminant process usually occurring in immunocompromised individuals. Risk factors include neutropenia, hematologic malignancies, uncontrolled diabetes mellitus, skin burns and deferoxamine therapy in dialysis patients. This case illustrates the importance of early suspicion of mucormycosis and immediate diagnostic bronchoscopic examination in cases of rapidly progressing pulmonary infiltrates in COPD patients on low doses of corticosteroids.

Effects of hypoxia on heparan sulfate in bovine aortic and pulmonary artery endothelial cells.

Newly synthesized heparan sulfates purified from the cell layer of bovine aortic endothelial cells (BAECs) and main pulmonary artery endothelial cells (BPAECs) cultured under either normoxic (21% oxygen) or hypoxic (3% oxygen) conditions were characterized by size, charge, and capacity to bind to antithrombin III. Incorporation of radiolabeled sulfate into cell layer-associated heparan sulfate was reduced by 70% in BAECs and by 45% in BPAECs during exposure to 3% oxygen; degradation of radiolabeled heparan sulfate was not affected by hypoxia. However, the percentage of total radiolabeled heparan sulfate that bound to antithrombin III was increased by 33% for BAECs and by 120% for BPAECs when compared with radiolabeled heparan sulfate synthesized during the 21% oxygen exposure. Both the high- and low-antithrombin III affinity radiolabeled heparan sulfate consisted of two components of different sizes; the low-affinity components (mean sizes, 60 and 40 kd) generated under normoxic conditions were smaller than their respective high-affinity components (mean sizes, 70 and 55 kd) by molecular sieve chromatography. The components of low-antithrombin III affinity heparan sulfate generated during exposure to 3% oxygen were increased in size compared with the corresponding low-affinity components generated during the 21% oxygen exposure for both BPAECs and BAECs. In addition, the amount of the larger high-antithrombin III affinity component was reduced in both cell types exposed to hypoxia. There was no difference in functional heparin-like activity per dish between cells cultured at 3% and 21% oxygen; BAECs had twofold to threefold greater activity per dish than did BPAECs at both levels of oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)

Young hamsters are more resistant than adults to endotracheally instilled porcine pancreatic elastase

We measured the physiologic and stereologic response to 0.1, 0.2, and 0.4 microgram of porcine pancreatic elastase instilled in a volume of 0.25 ml 0.9% NaCl/100 g body weight into the trachea of groups of young and adult hamsters. The young hamsters averaged 50 g and the adult hamsters 116 g in initial body weight. Twenty-one days after administration of elastase, lung volumes, static lung compliance, maximum expiratory flow, the whole section mean linear intercepts (MLI) were measured. The degree of emphysema increased in all animals as a function of dose. Examination of the lung volume and compliance dose-response characteristics indicated that young hamsters developed less physiologic change with increasing elastase dose than did adult hamsters. Maximum expiratory flow and whole section MLI dose-response were similar in the young and adult elastase-treated groups. However, the MLI in young hamsters treated with the 0.4 microgram elastase dose was decreased in the outer third of the lung compared to adult emphysematous hamsters. Also, mean airspace density relative to saline control values in young hamsters was double that found in adult hamsters treated with the 0.4 microgram elastase dose. Although serum alpha 1-globulin levels were equivalent in both young and adult normal hamsters, values normalized for lung elastin content were significantly increased in young animals. We conclude that young hamsters show less change in lung function as a function of elastase dose twenty-one days after elastase instillation. Possible reasons for this include an increased ratio of lung alpha 1-globulin/lung elastin in young hamsters, their continued ability to grow new alveoli, and age related differences in airway size favoring a central distribution of enzyme.

Stress-strain characteristics of normal and emphysematous hamster lung strips

A simple mathematical model of the one dimensional, stress-strain behavior of hamster lung tissue based on strain energy considerations was tested in degassed, uniaxially stretched strips obtained from normal and emphysematous hamster lungs cycled in saline. The relationship between Eulerian stress (sigma) and extension ratio (lambda) was found to take the form sigma = (lambda 2-1/lambda) x f(lambda) where the function f(lambda) was experimentally determined. Stress in six normal and five emphysematous strips was calculated by dividing the tension at each stretch increment by the strip cross-sectional area. Plotting sigma lambda/(lambda 2-1) versus a function of the form e eta lambda yielded a linear expression for f(lambda), me eta lambda + b, where n = 2. The complete stress-strain behavior of hamster lung strip tissue could then be expressed as a simple function of lambda over a range of lambda = 1.0-2.0: sigma = (lambda 2-1/lambda)(me2 lambda+b) The values of the constants m and b depend solely upon the mechanical properties of the elastic and collagen fiber networks in these atelectatic, saline cycled lung strips. The slope m = 0.151, and the intercept b = 0.416 in normal strips (r = 0.98). In emphysematous strips m = 0.016 and b = -0.199 (r = 0.82). Given the smaller m found for emphysematous strips, less strain energy accumulated with increasing stretch and did not even begin in these strips until lambda = 1.3. Further, the fit of the equation to the data was not as good for emphysematous as for normal strips. We conclude that the above equation adequately describes the stress-strain properties of normal hamster lung strips tissue but is not as good in emphysematous strips where the disease is patchy.

Spouses of persian gulf war I veterans : Medical evaluation of a U.S. cohort

Ten years after the 1991 Persian Gulf War (GW I), a comprehensive evaluation of a national cohort of deployed veterans (DV) demonstrated a higher prevalence of several medical conditions, in comparison to a similarly identified cohort of nondeployed veterans (NDV). The present study determined the prevalence of medical conditions among nonveteran spouses of these GW I DV and NDV. A cohort of 490 spouses of GW I DV and 537 spouses of GW I NDV underwent comprehensive face-to-face examinations. No significant differences in health were detected except that spouses of DV were less likely to have one or more of a group of six common skin conditions. We conclude that, 10 years after GW I, the general physical health of spouses of GW I DV is similar to that of spouses of NDV.

Differences in Outpatient Corticosteroid Prescribing Patterns Between Attending and House Staff Physicians as an Indicator of the Quality of Supervision

Computerized information systems have become an in-dispensable source of quality improvement data in the healthcare field. The degree to which we are successful in using these systems is limited only by our ability to ask the right questions. In this study, computerized patient records were used to evaluate the uniformity in the prescribing patterns for oral corticosteroids among house staff and attending physicians as a measure of the adequacy of resident supervision in the outpatient setting. Retrospective analysis of the records of 771 outpatients receiving prescriptions for oral corticosteroid preparations over 1 year in a large tertiary-care university-affiliated Department of Veterans Affairs Medical Center indicated different prescribing patterns for attending physicians and house staff. Additionally, it was noted that house staff tended to manage more complex patients than did attending physicians. We further evaluated the clinical outcomes of these patients to assess the quality, appropriateness, and comparability of care within cohorts of patients and to determine the degree to which resident supervision may have affected outcomes. The study results suggest that there is an opportunity to improve the management of patients treated with oral corticosteroid therapy by increasing staff physician involvement either through direct care of the most complex cases or through enhanced resident supervision.

Design of an x-ray / ventilator synchronization system in an integrated clinical environment

Patients in an ICU may receive daily chest x-rays. These x-rays are taken manually and may be at different phases of respiration, which limits their clinical usefulness. We examine design issues around automatically synchronizing an x-ray and ventilator in an interoperable manner, including requirements on the individual devices and new safety hazards introduced by connecting them into a system.

Comparison of contractile function of diaphragm and cardiac muscle in response to paired electrical stimulation

Paired pacing has been shown to potentiate contractile function of cardiac muscle, and it has been suggested that this may enhance contractile function of diaphragmatic muscle. The primary goal of this study was to study the effect of paired pacing on potentiation of contractile function of diaphragmatic muscle compared to atrial and ventricular myocardium. Diaphragmatic muscle was isolated from mouse and rat, and atrial and ventricular myocardium from dogs. Potentiation was induced by isolated extrastimuli (equal in duration and intensity to the pacing stimulus) and by repetitive extrastimuli (i.e. paired pacing) at a paced rate of 12, 30 and 60 beats/min. Baseline studies were performed while preparations were isometrically contracting at L(max) in oxygenated Krebs-Henseleit solution at 28 degrees C. Maximal force generation in response to a premature stimulus was determined at each rate by scanning the coupling interval between paced beats. Under baseline conditions, diaphragmatic muscle contracted faster than atrial and ventricular muscle. In all tissues, maximum potentiation (increase in force above baseline) was approximately 100% of baseline force, and peak potentiation occurred at shorter coupling intervals with increasing rates of stimulation. Single and paired pacing of diaphragm potentiated the contraction during which the extrastimuli were introduced, while in cardiac muscle, extrastimuli potentiated the contraction following the extrastimulus. The maximum potentiated response occurred when the extrastimulus was introduced prior to the development of peak force in diaphragmatic muscle. In contrast, in atrial and ventricular muscle, a single or paired premature stimulus potentiated the subsequent beat when delivered late during relaxation. In cardiac muscle, maximal potentiation gradually occurred following several repetitive stimuli. Following cessation of single and paired pacing, the beat following the potentiated response immediately returned to baseline in diaphragmatic muscle, while a gradual decline was evident over several subsequent beats in cardiac muscle. Increasing the bath temperature from 28 to 37 degrees C resulted in a leftward shift in the peak potentiated force vs. coupling interval curve without a decline in the magnitude of potentiated force in diaphragmatic muscle. In diaphragm muscle, exposure to ryanodine markedly decreased baseline force and maximal potentiation. We conclude that closely timed extrastimuli applied to diaphragmatic muscle can potentiate developed force in a given contraction, while in cardiac tissue a delayed stimulus potentiates the subsequent beat. These differences in contractile responsiveness are not due to differences in loading conditions, but appear to reflect intrinsic differences in calcium handling.