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Biomedical subjects

S A Moser

Publications and source records attributed to S A Moser.

54 records · Page 3Linked to original sources
PubMed1988

Implantable defibrillation: eight years clinical experience.

Implantation of the first automatic defibrillator occurred in February 1980. Incorporation of cardioversion capability in 1982 resulted in the AICD automatic implantable cardioverter defibrillator. Between April 1, 1982 and April 15, 1988, 3610 patients in 236 U.S. and 84 international centers received AICD pulse generators. Patient population consisted of 2904 males and 683 females with recurrent ventricular tachycardia and/or fibrillation, mean age 59 yrs. (range 9-96 yrs.). Primary diagnoses reported for the patient group were: coronary artery disease (63.5%), nonischemic cardiomyopathy (12.9%), other (6.4%) and unspecified (17.2%). Mean reported LV ejection fraction was 32.8%. Follow-up averaged 12.2 mo. (range 0-72 mo.). Of 385 deaths, 94 (24%) were sudden. Cumulative percentage survival (+/- S.E.) from sudden cardiac death (SCD) was 98.0 +/- 0.3%, 96.5 +/- 0.5%, 95.2 +/- 0.7%, 93.7 +/- 1.0%, 93.7 +/- 1.0% and 89.7 +/- 4.0% at 12, 24, 36, 48, 60 and 72 months, respectively. Operative mortality (less than or equal to 30 days) was 2.5%. Reported side effects/complications were similar to those of pacemakers. To date, 33% of the patients received spontaneous device countershocks. AICD pulse generator survival from electrical and mechanical failures was 92.8 +/- 0.5%, 88.4 +/- 0.7%, 86.7 +/- 0.8% and 86.4 +/- 0.9% at 12, 18, 24 and 30 mos. Data analysis demonstrates that the AICD has had a significant impact on patient survival from SCD.

Death, Sudden↗
PubMed1988

Fungal-strain-dependent alterations in the time course and mortality of chronic murine pulmonary blastomycosis.

Intratracheal injection of 10(4) conidia of Blastomyces dermatitidis strain M1-A into mice was shown in previous work to induce chronic pulmonary and disseminated infection with histopathologic features of chronic human blastomycosis. Furthermore, 10-fold variations in inoculum density produced marked changes in mean survival times (MSTs), i.e., 32 days at 10(6), 36 days at 10(5), 97 days at 10(4), and 172 days at 10(3). A second strain (M1-B) failed to induce death in this model. To assess fungal-strain-dependent virulence, we extended these previous studies to 11 additional human isolates. Groups of male BALB/cByJ mice (6 to 8 weeks old) were injected intratracheally with 10(4) conidia from each of the 13 strains; the mice were weighed weekly and monitored for mortality, and their lungs were examined histopathologically. Infection rate and mortality were 100% in all groups except for the M1-B inoculated mice. For strains M1-B and M1-A, MST and mortality curves were not significantly different from those observed in our previously reported experiments. Four different survival patterns were noted in infected mice. The shortest MSTs were produced by strains M2-E, M2-B, M2-K, M2-H, and M2-A (24, 26, 26, 27, and 31 days, respectively), and the longest MST was seen in animal groups inoculated with strains M2-J and M2-G (130 and 134 days, respectively). Strains M2-I, M2-F, and M2-D produced intermediate MSTs of 65, 79, and 80 days, respectively. The 107-day MST induced by M1-A did not differ from strain M2-C-induced MST but differed significantly from the MST produced by the other strains. Pulmonary histopathology was similar in all animals dying with blastomycosis. The wide spectrum in survival times was not related to differences in clinical status of the patient from whom the isolate had been obtained, to fungal inoculum viability, or to individual mouse weight at inoculation. Strain-dependent virulence factors present in these fungal isolates alter the disease course in inbred mice in a fashion similar to that induced by 10-fold inoculum variation of strain M1-A conidia. These 13 isolates of B. dermatitidis, 1 avirulent and 12 with differing levels of virulence, provide tools for future studies into the nature of fungal virulence determinants in chronic blastomycosis.

Animals↗
PubMed1987

Chronic murine pulmonary blastomycosis induced by intratracheally inoculated Blastomyces dermatitidis conidia.

Groups of 6-wk-old male BALB/cByJ mice were injected intratracheally (IT) with viable conidia from Blastomyces dermatitidis strains (FW or CR) harvested from 2-wk-old cultures (Pine-Drouhet agar at 30 degrees C) and separated from hyphal elements by polycarbonate filtration (5 micron). Inocula (0.05 ml) were 93 to 97% conidia in nonpyrogenic normal saline (NPNS) with greater than 90% viability. Quantitative cultures of the lungs and trachea of mice killed immediately after injection of 10(4) conidia (FW) confirmed that the inoculum was evenly distributed between the lungs, with virtually no conidia retained in the trachea. Animals were observed for 354 days for weight change, mortality, extrapulmonary dissemination and histopathologic changes. Mice inoculated with 10(4) FW began dying on Day 44, with a median survival of 92 days. A decrease in mean weight compared with that in control mice was noted by Day 55. In contrast, mice inoculated with 10(4) CR or NPNS neither died with blastomycosis nor lost weight in 329 days. Variation of the FW inoculum by tenfold increments produced comparable dose-dependent alterations in both mortality rate and weight change curves. Fifty percent survival was 32, 36, 92, or 172 days for mice inoculated with 10(6), 10(5), 10(4), or 10(3) conidia, respectively. Dissemination from the lungs to the liver, spleen, kidney, testis, and brain was found in the cachectic mice that were killed. Pathologic features of pulmonary and disseminated infections were comparable to those in human disease. This quantitative, reproducible model of chronic murine blastomycosis mimics the human disease in many respects and should provide a basis for future studies of the immunology, pathogenesis, and therapy of chronic blastomycosis.

Animals↗
PubMed1984

Mexiletine for recurring ventricular arrhythmias: assessment by long-term electrocardiographic recordings and sequential electrophysiologic studies.

Mexiletine, an oral lidocaine-like drug, was initially thought to be effective treatment for recurring ventricular arrhythmias. Recent work has cast doubt on its efficacy. We administered mexiletine to 32 patients with chronically recurring ventricular arrhythmias. In 22 patients with no history of syncope or documented sustained ventricular arrhythmia (group 1), mexiletine was effective in only 27% (six patients) as assessed by 24-hour ambulatory ECG recordings before and during mexiletine treatment. Ten other patients had a history of syncope or documented sustained ventricular tachycardia or ventricular fibrillation. Only 10% (one patient) responded to mexiletine based on sequential electrophysiologic studies with programmed ventricular stimulation. Four of the seven patients responding to mexiletine had not received prior antiarrhythmic therapy. We conclude that mexiletine has limited efficacy in the treatment of recurring drug-refractory ventricular arrhythmias.

Adult↗
PubMed1984

Disturbances in the hypothalamic-pituitary-gonadal axis in male patients with acute renal failure.

The function of the hypothalamic-pituitary-gonadal (HPG) axis was examined in 20 male patients with acute renal failure. During the oliguric phase of the disease, the serum concentrations of follicle stimulating hormone (FSH) and total and unbound testosterone were markedly reduced, those of prolactin were elevated while those of luteinizing hormone (LH) were normal. The serum concentrations of sex hormone binding globulin were normal. During the diuretic phase of the illness, the serum levels of FSH and testosterone remained low but those of prolactin fell towards normal. After recovery of renal function, the abnormalities in the serum concentrations of these hormones were reversed. The responses of LH and FSH to gonadotropin releasing hormone and of prolactin to thyrotropin releasing hormone were abnormal and became normal after recovery of renal function. The results demonstrate that: (1) abnormalities in HPG axis occur early in the course of acute renal failure; (2) many features of these derangements are similar to those seen in chronic renal failure, and (3) the alterations in the function of the HPG axis are reversible when renal function is restored. The data suggest that loss of renal function, uremia per se and/or a metabolic consequence of uremia such as secondary hyperparathyroidism are responsible for these derangements.

Acute Kidney Injury↗
PubMed1982

Immunization of mice by intracutaneous inoculation with viable virulent Cryptococcus neoformans: immunological and histopathological parameters.

Immune responses, including protection and delayed hypersensitivity, were evaluated in experimental murine cryptococcosis. Mice were immunized by the intracutaneous inoculation of viable virulent Cryptococcus neoformans yeasts. Response to the cutaneous infection was evaluated histologically and by cultural assays of the internal organs, as well as by intravenous challenge with the same strain. Protection was assessed by survival, histopathology, and quantitative organ culture. The intracutaneous inoculation of cryptococci resulted in a local inflammatory response that effectively limited dissemination of the organisms systemically and induced the development of delayed hypersensitivity demonstrable with a membrane extract of C. neoformans and with soluble cytoplasmic substances. A protective response was induced by the cutaneous inoculation of cryptococci as well, in that immunized animals survived longer, with about 25% of the challenged group ridding themselves completely of the cryptococci. Protection could be demonstrated by cultural analyses, but all animals, whether control or immunized, allowed considerable multiplication of the inoculum during the first 4 weeks after intravenous challenge. It would appear, therefore, that the protective mechanism(s) required additional antigenic stimulation before it could eventually function to eliminate all cryptococci from tissues. Histologically, there were no differences in pathology of the internal organs between immunized and unimmunized animals. Although the model described herein for the induction of immune responses in murine cryptococcosis has at least one drawback, viz., the presence of cryptococci in the skin lesion of many animals throughout the duration of the experiment, it does have the advantage that the immune responses were stimulated by a virulent strain and only minimal dissemination occurred. Therefore, lymphocytes could be removed from animals that were not contaminated with cryptococci for in vitro and in vivo transfer.

Animals↗
PubMed1980

Experimental murine candidiasis: cell-mediated immunity after cutaneous challenge.

Male CBA/J mice, sensitized by cutaneous inoculation with viable Candida albicans blastospores, were used to study in vivo and in vitro cellular immune responses. Three antigens of C. albicans, viz., a cell wall glycoprotein (GP), a membrane extract (ppt-HEX), and soluble cytoplasmic substances (SCS), were used in vitro in a lymphocyte stimulation assay, whereas the GP and ppt-HEX were used in vivo to detect delayed hypersensitivity by the footpad assay. Delayed hypersensitivity to GP and ppt-HEX was transferred from sensitized donors to naive recipients with peritoneal exudate cells and not with serum. Moreover, the transfer of the reactivity to ppt-HEX was abrogated by the prior treatment of the transfer suspension with anti-theta 1.2 serum and complement. The in vitro lymphocyte response to GP and ppt-HEX correlated qualitatively with the in vivo responses. SCS, a preparation shown to be ineffective in vivo previously, did stimulate lymphocytes from sensitized animals in vitro. The in vitro response to Candida antigens, as well as phytohemagglutinin, was abolished by treatment of the lymphocyte suspension with anti-thymocyte 1.2 serum before assay, whereas anti-immunoglobulin serum had less effect on these responses. The in vivo and in vitro reactivity to the Candida antigens, therefore, was dependent upon viable T-lymphocytes. Preliminary specificity studies were carried out in the lymphocyte stimulation assay, using lymphocytes from mice infected with C. albicans tested against ppt-HEX preparations extracted from two other species of Candida, C. tropicalis and C. guillermondii, and from two other pathogenic yeast forms, Histoplasma capsulatum and Blastomyces dermatitidis. Significant cross-reactivity was observed with C. tropicalis only, a species which is known to be serologically related to C. albicans.

Animals↗
PubMed1980

Effects of cyclophosphamide on murine candidiasis.

Male CBA/J mice were given a single dose of 200 mg of cyclophosphamide (CY) per kg 3 days before a first or second cutaneous inoculation with viable Candida albicans in an attempt to suppress antibody formation and determine the effects of such suppression on the development of acquired immunity. After cutaneous inoculation, mice not treated with CY developed acquired immunity to intravenous challenge, which was accompanied by the development of circulating antibodies, delayed hypersensitivity, and in vitro responsiveness of lymph node cells to Candida antigens. CY treatment resulted in an immediate depression of peripheral blood leukocytes, with polymorphonuclear leukocytes and monocytes rebounding quickly to normal or above normal levels while lymphocyte remained depressed throughout the 4-week observation period. In vitro stimulation of lymph node cells from CY-treated mice was depressed shortly after treatment; however, responses to phytohemagglutinin and three Candida antigens (a cell wall preparation, a membrane preparation, and soluble cytoplasmic substances) recovered, whereas the responses to lipopolysaccharide did not. CY effects on the cutaneous lesion were twofold; first, the number of viable Candida cells in the lesions was much higher in animals receiving CY 3 days before Candida inoculation, and second, the size of the dermal lesion was either greatly enhanced or reduced depending upon the time of CY treatment relative to the number of cutaneous Candida inoculations. CY-treated animals developed higher levels of delayed hypersensitivity to the membrane preparation when infected once cutaneously than did corresponding untreated animals. The number of mice responding with circulating antibodies to soluble cytoplasmic substances after cutaneous inoculation was greatly reduced in CY-treated groups, and this impaired ability to produce antibodies correlated with the poor survival of these mice after intravenous challenge. Our results suggest that the ability to produce antibody at the time of challenge is crucial to successful defense against systemic candidiasis in this murine model.

Animals↗
PubMed1978

Isolation of glycopeptides with skin test activity from dermatophytes.

By using ethylene glycol extraction of whole submerged cultures followed by Sephadex G-200 and diethylaminoethyl-Sephadex chromatography, we isolated four distinct glycopeptides from Trichophyton mentagrophytes, T. rubrum, and Microsporum canis. Chemical analyses revealed that these glycopeptides contained mostly carbohydrate (42.5 to 81.6%) and protein (4.3 to 11.3%), with lesser amounts of phosphorus (0.4 to 6.0%) and hexosamines (0.3 to 0.6%). Based upon total carbohydrate and monosaccharide content, these dermatophyte glycopeptides could be divided into two chemical groups: glucopeptides (DSI1) and mannopeptides (DSI2, DSII1, and DSII2). The mannopeptides and glucopeptides of each species of dermatophyte were not significantly different chemically from those derived from the other two dermatophyte species studied. Skin testing of DSI1-glycopeptides or DSI2-mannopeptides in immunized guinea pigs indicated that only the DSI2-mannopeptides elicited a delayed hypersensitivity reaction. Skin testing T. mentagrophytes 62-infected guinea pigs with the four purified DS-glycopeptides, as well as earlier fractions from the purification scheme, derived from T. mentagrophytes, T. rubrum, and M. canis, again indicated that only the DSI2-mannopeptides of the two Trichophyton species elicited a delayed hypersensitivity reaction. The number of infections or duration of infection had no effect on the size of the skin test response. DSI2-mannopeptides were non-cross-reactive between genera when tested in Trichophyton-immunized or -infected guinea pigs and Microsporum-immunized guinea pigs.

Animals↗
PubMed1978

Experimental murine candidiasis: cell-mediated immunity after cutaneous challenge.

Attempts were made to isolate an antigen(s) from Candida albicans suitable for detecting hypersensitivity in a murine model of candidiasis. Using footpad reactivity in cutaneously infected animals as the assay, comparisons were made of two commercial extracts and cell wall and cytoplasmic preparations made in the laboratory. An extract of the cell wall, a glycoprotein (GP) removed with ethylenediamine, and an extract prepared from the membrane fraction of disrupted C. albicans blastospores proved most useful in demonstrating delayed hypersensitivity in the murine model. The activity of the GP fraction was considerably reduced by oxidation with periodate and was abrogated entirely by digestion with proteolytic enzymes. The extract from the membrane fraction was obtained by incubating the insoluble membrane fraction with phosphate-buffered saline, pH 7.4, at 50 degrees C, and the proteins in the extract were subsequently precipitated with ammonium sulfate to yield a test preparation that was approximately 75% protein and 25% carbohydrate. The precipitated extract was designated ppt-HEX. Footpad reactivity to ppt-HEX could be transferred with cells and not with serum if the cells were taken from animals at the appropriate time after sensitization. Since the membrane and GP fractions appear to elicit true delayed hypersensitivity reactions, further investigations into their specificity and biochemistry seem warranted.

Animals↗
PubMed1978

Experimental murine candidiasis: pathological and immune responses in T-lymphocyte-depleted mice.

Mice depleted of T-lymphocytes by thymectomy and irradiation (TXB) and immunologically competent mice were compared for gross and histological pathology as well as immune responses after cutaneous and/or intravenous challenge with Candida albicans. In response to a first cutaneous inoculation with viable Candida, TXB, sham-operated (SXB), and unmanipulated (normal) mice, all developed lesions of comparable size, duration, and histopathology. When challenged a second time cutaneously, normal and SXB mice developed lesions which were greatly increased in size when compared with those produced by a first cutaneous infection, whereas TXB mice developed lesions comparable in size to those initiated by the first infection. Histologically, the first and second lesions in all animals were acute abscesses predominantly comprised of polymorphonuclear leukocytes. The larger second lesions in SXB and normal mice were accompanied by detectable circulating antibody and by delayed hypersensitivity. Neither circulating antibody nor delayed hypersensitivity were stimulated in the TXB mice. When challenged intravenously, all previously uninfected mice, regardless of T-cell status, were equally susceptible to C. albicans. Contrary to SXB or normal mice, however, TXB mice which had been infected cutaneously were not more resistant to a subsequent intravenous challenge as judged by 6-week survival. The results suggest that T-cells do not play a significant role in innate resistance of mice to systemic candidiasis, but that such cells are important in the development of acquired resistance.

Antibodies, Fungal↗
PubMed1978

Atypical isolate of Cryptococcus neoformans cultured from sputum of a patient with pulmonary cancer and blastomycosis.

Cryptococcus neoformans was isolated repeatedly from a patient with epider-moid carcinoma and pulmonary blastomycosis. The isolate was atypical in that it had only a minute capsule, caused persistent infection but no perceptible disease in mice, and initially appeared not to assimilate trehalose. Only after an incubation of 2 to 3 weeks did utilization of this substrate become apparent.

Aged↗
PubMed1978

A rapid radiometric technique used to trap and quantitate 14CO2 evolved by slow-growing microorganisms.

An apparatus to trap and quantitate 14CO2 is described. When used to measure antibiotic effects on Histoplasma capsulatum and Mycobacterium bovis (BCG), there was an inverse quantitative relationship between 14CO2 evolved and antibiotic concentration. The technique should prove useful for analyses that require trapping and quantitation of 14CO2, including antimicrobial sensitivities of slow-growing organisms.

Amphotericin B↗
PubMedDate not supplied

Association rules and data mining in hospital infection control and public health surveillance.

OBJECTIVES: The authors consider the problem of identifying new, unexpected, and interesting patterns in hospital infection control and public health surveillance data and present a new data analysis process and system based on association rules to address this problem. DESIGN: The authors first illustrate the need for automated pattern discovery and data mining in hospital infection control and public health surveillance. Next, they define association rules, explain how those rules can be used in surveillance, and present a novel process and system--the Data Mining Surveillance System (DMSS)--that utilize association rules to identify new and interesting patterns in surveillance data. RESULTS: Experimental results were obtained using DMSS to analyze Pseudomonas aeruginosa infection control data collected over one year (1996) at University of Alabama at Birmingham Hospital. Experiments using one-, three-, and six-month time partitions yielded 34, 57, and 28 statistically significant events, respectively. Although not all statistically significant events are clinically significant, a subset of events generated in each analysis indicated potentially significant shifts in the occurrence of infection or antimicrobial resistance patterns of P. aeruginosa. CONCLUSION: The new process and system are efficient and effective in identifying new, unexpected, and interesting patterns in surveillance data. The clinical relevance and utility of this process await the results of prospective studies currently in progress.

Data Interpretation, Statistical↗
PubMedDate not supplied

Application of data mining to intensive care unit microbiologic data.

We describe refinements to and new experimental applications of the Data Mining Surveillance System (DMSS), which uses a large electronic health-care database for monitoring emerging infections and antimicrobial resistance. For example, information from DMSS can indicate potentially important shifts in infection and antimicrobial resistance patterns in the intensive care units of a single health-care facility.

Alabama↗
PubMedDate not supplied

Automating clinical practice guidelines: a corporate-academic partnership.

Implementation of guidelines offers one of the largest opportunities for quality improvement, utilization review, and cost control for the health-care enterprise. If guidelines could be implemented on a large scale, their adoption could result in $100 billion in annual savings as well as improve the quality of patient care. However, infrastructural barriers impede progress. Collaboration between the Laboratory Medicine Health Services Program at the University of Alabama at Birmingham, Columbia-Presbyterian Medical Center, and the Cerner Corporation, funded by the National Institute of Standards and Technology as part of the Advanced Technology Program involving ¿Information Infrastructure for Healthcare,¿ is focused on developing and delivering: 1) methods for creating operational forms of guidelines; 2) an effective computer-based architecture for implementing guidelines in clinical practice; 3) methods for packaging guidelines for wide distribution; 4) methods for testing the efficacy, safety, and acceptability of guidelines; and 5) a model for collecting, aggregating, and normalizing data from disparate systems. This hypothesis-driven research program is focused on laboratory medicine-based guidelines as a tool for developing, testing, and evaluating methods that can be implemented widely.

Academic Medical Centers↗