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Biomedical subjects

M L Lewis

Publications and source records attributed to M L Lewis.

At least 19 recordsLinked to original sources

Cytokine secretion by immune cells in space.

Cultured, bone marrow-derived macrophages, murine spleen and lymph node cells, and human lymphocytes were tested for their ability to secrete cytokines in space. Lipopolysaccharide-activated bone marrow macrophages were found to secrete significantly more interleukin-1 and tumor necrosis factor when stimulated in space than when stimulated on earth. Murine spleen cells stimulated with poly I:C in space released significantly more interferon-alpha at 1 and 14 hours after stimulation than cells stimulated on earth. Similarly, murine lymph node T cells and human peripheral blood lymphocytes, stimulated with concanavalin A in space, secreted significantly more interferon-gamma than ground controls. These data suggest that space flight has a significant enhancing effect on immune cell release of cytokines in vitro.

Animals

The role of bronchoscopy in the diagnosis of pulmonary tuberculosis in patients at risk for HIV infection.

The present study was undertaken to clarify the role of bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) in the diagnosis of pulmonary tuberculosis in patients at risk for human immunodeficiency virus (HIV) infection. We retrospectively identified 31 patients at risk for HIV who proved to have Mycobacterium tuberculosis on culture of at least one pulmonary specimen. All had pulmonary symptoms but initial sputum smears negative for acid-fast bacilli (AFB). All underwent fiberoptic bronchoscopy (FOB), including BAL and TBB; postbronchoscopy sputum was also collected in 19 patients. A specimen was considered to yield an immediate diagnosis when positive for AFB either on smear or histologic study; granulomas alone were considered positive when no other causes were identified. Overall, an immediate diagnosis was made by bronchoscopic specimens in 15 (48 percent) of 31 cases. TBB was the sole positive specimen in seven patients (23 percent). For comparison, similar specimens from 40 patients in whom M avium complex (MAC) grew on culture were also evaluated. An immediate identification of AFB was made in only four patients (10 percent). We conclude that the finding of AFB on staining of any pulmonary specimen is highly suggestive of tuberculosis, rather than MAC, and warrants institution of antituberculosis therapy. Of all bronchoscopic specimens, TBB provides the highest yield for an immediate diagnosis of tuberculosis.

Acquired Immunodeficiency Syndrome

Missile attack.

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Combat Disorders

Pulmonary disposition of gallium-67 in patients with Pneumocystis pneumonia: an analysis using bronchoalveolar lavage.

Gallium-67 localizes to the cellular fraction of bronchoalveolar lavage (BAL) fluid in patients with sarcoidosis, idiopathic pulmonary fibrosis, as well as normal subjects. To further study 67Ga disposition in BAL fluid, 11 patients with Pneumocystis carinii pneumonia (PCP) and 8 patients with a variety of other lung diseases, underwent BAL 24 hr after 67Ga injection. Compared to the non-PCP patients, PCP patients had high uptake gallium scans at 24 and 72 hr, and showed significantly increased radioactivity in both unfractionated lavage and in the acellular, supernatant fraction of BAL. The mean ratio of total supernatant/cell pellet radioactivity was also higher in patients with PCP (1.23 +/- 0.27 versus 0.24 +/- 0.05, p less than 0.01). Supernatant radioactivity correlated with the presence of neutrophil alveolitis, but not with BAL transferrin concentrations. We conclude that neutrophil alveolitis in PCP promotes 67Ga accumulation in the acellular fraction of BAL fluid. However, the high uptake 67Ga scans observed in PCP patients without neutrophil alveolitis suggest that the mechanism of pulmonary uptake of 67Ga is not fully elucidated by BAL fluid analysis alone.

Adult

Experiments with suspended cells on the Space Shuttle.

Spaceflight experiments since 1981 have demonstrated that certain cell functions are altered by micro-g. Biophysical models suggest that cell membranes and organelles should not be affected directly by gravity, however, the chemical microenvironment surrounding the cell and molecular transport could be altered by reduced gravity. Most experiments have used suspended live cells in small chambers without stirring or medium exchange. Flight results include increased attachment of anchorage-dependent human cells to collagen coated microcarriers, reduced secretion of growth hormone from pituitary cells, decreased mitogenic response of lymphocytes, increased Interferon-alpha by lymphocytes, increased Interleukin-1 and Tumor Necrosis Factor secretion by macrophages. Related experiments on cells immediately postflight and on procaryotic cells have shown significant changes in secretory capacity, cell proliferation, differentiation and development. Postulated mechanism include altered cell-cell interactions, altered calcium ion transport, effects on cell cytoskeleton, transport of transmitters and interactions with receptors. The discussion includes use of new molecular methods, considerations for cell environmental control and a preview of several experiments planned for the Shuttle and Spacelab flights to study the basic effects of microgravity on cellular physiology and potential interactions of spaceflight with radiation damage and cellular repair mechanisms.

Animals

A miniaturized fibrinolytic assay for plasminogen activators.

This report describes a micro-clot lysis assay (MCLA) for evaluating fibrinolytic activity of plasminogen activators (PA). Fibrin clots were formed in wells of microtiter plates. Lysis of the clots by PA, indicated by change in turbidity (optical density, OD), was monitored with a microplate reader at five minutes intervals. Log-log plots of PA dilution versus endpoint, the time at which the OD value was halfway between the maximum and minimum value for each well, were linear over a broad range of PA concentrations (2-200 International units/ml). The MCLA is a modification and miniaturization of well established fibrinolytic methods. The significant practical advantages of the MCLA are that it is a simple, relatively sensitive, non-radioactive, quantitative, kinetic, fibrinolytic micro-technique which can be automated.

Chromogenic Compounds

A computer program for microplate reader interface and analysis of kinetic, microclot lysis assays.

This paper describes the development and use of a program for the APPLE IIe computer which records and analyzes data from an automated microplate reader for the purpose of determining the time required for clots formed in microplate wells to half lyse as determined by optical density readings. The use of this software has led to significant savings of technician time over that required for nonautomated systems.

Electronic Data Processing

A behavioral comparison of the helping styles of nursing students, psychotherapists, crisis interveners, and untrained individuals.

Helping styles of nursing students were compared with those of subjects in a prior study (17 psychotherapists, 12 crisis interveners, and 15 untrained people). Subjects were 30 junior-year college students in the second part of a two-course sequence in interpersonal relations. The subjects were videotaped in a 3-minute interaction with a simulated client. An experienced psychotherapist who was trained in the use of the Helping Skills Verbal Response System instrument rated each student. The helping behaviors of nursing students were found to resemble those of trained mental health practitioners; their behavior was significantly different from those of untrained individuals, who were highly verbose, directive, and used minimal reflection of affect or content.

Adult

Parallel line analysis: multifunctional software for the biomedical sciences.

An easy to use, interactive FORTRAN program for analyzing the results of parallel line assays is described. The program is menu driven and consists of five major components: data entry, data editing, manual analysis, manual plotting, and automatic analysis and plotting. Data can be entered from the terminal or from previously created data files. The data editing portion of the program is used to inspect and modify data and to statistically identify outliers. The manual analysis component is used to test the assumptions necessary for parallel line assays using analysis of covariance techniques and to determine potency ratios with confidence limits. The manual plotting component provides a graphic display of the data on the terminal screen or on a standard line printer. The automatic portion runs through multiple analyses without operator input. Data may be saved in a special file to expedite input at a future time.

Data Interpretation, Statistical

Herpes simplex virus type 1. A cause of the acute retinal necrosis syndrome.

The authors have isolated herpes simplex virus type 1 (HSV-1) from the vitreous of two patients with acute retinal necrosis. Clinical and laboratory data suggest that one case represented a primary HSV-1 infection, whereas the other case appeared to be a recurrent HSV-1 infection. In the primary case, changes on magnetic resonance imaging (MRI) suggest spread of the virus posteriorly to both optic tracts and the lateral geniculate ganglia. This case shares many features with the "von Szily" experimental model for HSV retinitis in the mouse.

Acyclovir

Prognosis of patients with AIDS requiring intensive care.

The Acute Physiology and Chronic Health Evaluation (APACHE) II classification, a measure of severity of illness in patients requiring intensive care, was devised before the rapid expansion of the acquired immunodeficiency syndrome (AIDS) epidemic. To determine the applicability of the APACHE II system to AIDS, we related observed in-hospital death rates to those predicted by APACHE II in 83 patients with AIDS. In a control group of patients without AIDS (n = 166) mean predicted and observed death rates (34.1 vs 31.3 percent) were similar. For the AIDS group overall observed mortality (63.9 percent) was significantly greater than that predicted by APACHE II (45.8 percent). The subgroup with Pneumocystis pneumonia requiring mechanical ventilation (n = 37) had an observed mortality (86.5 percent) that significantly exceeded the predicted value (44.3 percent), whereas all other AIDS patients (n = 46) showed similar predicted and observed death rates (47.0 vs 45.7 percent). APACHE II prediction of death rate also matched observed mortality in mechanically ventilated patients without Pneumocystis infection. The discrepancy between predicted and observed mortality in patients with Pneumocystis pneumonia requiring mechanical ventilation is most likely due to the lack of an APACHE II diagnostic category that accurately reflects the severity of this disease. A new diagnostic category that provides accurate outcome prediction in this patient group would form a basis for evaluation of new therapeutic interventions.

Acquired Immunodeficiency Syndrome

Multichannel extracochlear implant.

The transcutaneous eight-channel extracochlear implant has undergone continuous revision to simplify the surgical technique, to minimize patient morbidity, and to improve performance. The extracochlear electrode array has been miniaturized so that it can be inserted through the facial recess without disturbing the external auditory canal, tympanic membrane, or malleus. The use of the remote antenna placed around the external auditory canal has greatly increased battery life and patient comfort. With its simplified incisions, the surgical procedure can be performed as out-patient surgery. Preoperative cochlear nerve testing and use of evoked response cochlear nerve testing allow preadjustment of the speech processor. Current features and performance of the implant are discussed.

Acoustic Stimulation

Visual results and complications after retinal reattachment in the acute retinal necrosis syndrome. The influence of operative technique.

The authors compare the complications and visual results encountered in a consecutive series of 16 eyes undergoing retinal reattachment surgery for retinal detachment associated with the acute retinal necrosis syndrome. Eight eyes were treated with scleral buckling, vitrectomy, and cryotherapy with or without gas injection. Eight consecutive eyes (with one exception) were treated by the combination of vitrectomy, gas injection and laser photocoagulation with or without primary lensectomy and not subjected to scleral buckling as a primary procedure. The final reattachment rate was 93.8% (15 of 16 eyes) with no significant difference between the primary scleral buckle group (87.5%) and the non-buckle group (100%). Retinal reoperation and complication rates were higher in the primary buckle group and final visual acuities better in the non-buckle group despite comparable preoperative characteristics.

Adolescent

Vitrectomy for retinal detachment associated with acute retinal necrosis.

Six patients with retinal detachment associated with the acute retinal necrosis syndrome were treated by the combination of vitrectomy, gas injection, and laser photocoagulation. The retinas were successfully reattached in each patient with one operation. Five of the patients achieved a visual acuity of 20/200 or better, and three had a visual acuity of 20/40 or better.

Adolescent

The sequential use of estradiol and prostaglandin E2 topical gels for cervical ripening in high-risk term pregnancies requiring induction of labor.

We compared the safety and efficiency of 200 mg of estradiol valerate prepared as a topical cervical gel as a preripening agent when used 6 hours before the application of 2 mg of prostaglandin E2 gel for the purpose of cervical ripening in 40 high-risk obstetric patients before indicated oxytocin induction of labor. When compared with a placebo prostaglandin E2 dosage, the estradiol had no effect on the change of Bishop score, length of labor, amount of oxytocin required, or the cesarean delivery rate. While no uterine contractions were noted after the application of the estradiol, 85% of patients had recordable uterine activity after the application of prostaglandin E2, suggesting that even at the 2 mg dosage this sequential regimen is not appropriate for local cervical ripening.

Administration, Topical

Correlation of bronchoalveolar lavage cell populations with clinical severity of Pneumocystis carinii pneumonia.

We correlated bronchoalveolar lavage (BAL) cell populations with clinical course and outcome in 19 patients with Pneumocystis carinii pneumonia and acquired immunodeficiency syndrome. Twelve patients demonstrated an elevated (greater than or equal to 5 percent) BAL combined neutrophil and eosinophil count, which correlated with the magnitude of the alveolar-arterial PO2 gradient. Patients with elevated BAL granulocytes also had significantly higher serum lactate dehydrogenase levels. Three of the four patients who died had the highest percentage of neutrophil counts observed in lavage fluid. Although no patient was thought to have a concurrent bacterial infection, potential pathogens were cultured from the sputum of patients with the most elevated neutrophil counts. Whether BAL granulocytes reflect an inflammatory process analogous to the adult respiratory distress syndrome or signify concomitant bacterial infection remains to be determined. We conclude that BAL granulocytes are associated with more severe respiratory compromise in patients with Pneumocystis carinii pneumonia.

Acquired Immunodeficiency Syndrome

Elevated lactate dehydrogenase values in patients with Pneumocystis carinii pneumonia.

We investigated the source of elevated serum lactate dehydrogenase (LDH) levels in seven patients with Pneumocystis carinii pneumonia (PCP) by analyzing blood and bronchoalveolar lavage (BAL) albumin (ALB) and LDH, with isoenzyme fractionation. Four patients with non-PCP lung disease served as control subjects. In PCP patients, BAL LDH was sixfold higher, and BAL ALB, fourfold higher than in the non-PCP patients. The increased LDH/ALB in BAL as compared to serum, in addition to a BAL isoenzyme pattern characteristic of lung, suggest that BAL LDH arises from a pulmonary source. We postulate that the high correlation observed between BAL and serum LDH (r = 0.93, p less than 0.001) reflects backflow of pulmonary-derived LDH into the blood through an alveolocapillary membrane (ACM) compromised by PCP. Furthermore, a comparison of BAL LDH/ALB for each isoenzyme with the same serum ratio showed less backflow for the cationic isoenzymes. The ACM appears to sieve proteins on an electrical basis which may account for the LDH isomorphic pattern observed in the serum of PCP patients.

Acquired Immunodeficiency Syndrome

Continuous flow electrophoretic separation of proteins and cells from mammalian tissues.

A new continuous flow electrophoretic separator for cells and macromolecules was built and tested in laboratory experiments and in the microgravity environment of space flight. Buffer flows upward in a 120-cm long flow chamber, which is 6 cm wide X 1.5 mm thick in the laboratory version and 16 cm wide X 3.0 mm thick in the microgravity version. Electrophoretic subpopulations are collected in 197 fractions spanning 16 cm at the upper end of the chamber. The electrode buffer is recirculated through front and back cooling chambers, which are also electrode chambers. Ovalbumin and rat serum albumin were used as test proteins in resolution and throughout tests; resolution of these two proteins at 25% total w/v concentration in microgravity was the same as that found at 0.2% w/v concentration in the laboratory. Band spreading caused by Poiseuille flow and conductance gaps was evaluated using polystyrene microspheres in microgravity, and these phenomena were quantitatively the same in microgravity as in the laboratory. Rat anterior pituitary cells were separated into subpopulations enriched with cells that secrete specific hormones; growth-hormone-secreting cells were found to have high electrophoretic mobility, whereas prolactin-secreting cells were found to have low electrophoretic mobility. Cultured human embryonic kidney cells were separated into several electrophoretic subfractions that produced different plasminogen activators; a medium-high-mobility subpopulation and a medium-low-mobility subpopulation each produced a different molecular form of urokinase, whereas a high- and an intermediate-mobility subpopulation produced tissue plasminogen activator. Canine pancreatic islets of Langerhans cells were separated into subpopulations, which, after reaggregation into pseudoislets, were found to be enriched with cells that secrete specific hormones; insulin-secreting beta cells were found in lowest mobility fractions, whereas glucagon-secreting alpha cells were found in the highest mobility fractions. Results of particle electrophoresis experiments were comparable in microgravity and in the laboratory, since cell densities that overloaded the carrier buffer (resulting in zone sedimentation) were avoided, and a 500-fold increase in protein throughput was achieved without compromising resolution in microgravity.

Animals