Biomedical subjects
S A Moser
Publications and source records attributed to S A Moser.
When to use fluconazole.
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Usefulness of follow-up electrophysiologic study and event monitoring after successful radiofrequency catheter ablation of supraventricular tachycardia. Atakr Multicenter Investigators Group.
We assessed the usefulness of routine follow-up electrophysiologic studies after successful catheter ablation for supraventricular tachycardia and the role of event monitoring as an alternative modality in 310 patients at 11 centers using an investigational catheter ablation system with closed-loop temperature control. A routine follow-up electrophysiologic study between 1 and 3 months after ablation was required as part of the study protocol, and patients developing palpitations after ablation were encouraged to use event monitors. Recurrence of the initially targeted arrhythmia developed in 23 patients (7.4%) at a mean of 1.5 +/- 1.5 months after ablation. However, only 2 of these 23 recurrences were discovered by routine follow-up electrophysiologic study in asymptomatic patients (both with concealed accessory pathways); in the remaining 21 patients a positive follow-up electrophysiologic study was heralded by either recurrent symptoms, documented recurrent supraventricular tachycardia, and/or preexcitation on the electrocardiogram. Eighteen patients complained of palpitations after ablation and received an event monitor, which correctly diagnosed another cause of palpitations and ruled out recurrence of the ablated arrhythmia in 8 patients. Thus, the combination of clinical follow-up and event monitoring appears to be an effective alternative to routine follow-up electrophysiologic studies after catheter ablation of supraventricular tachycardia.
Comparison of four DNA-based methods for strain delineation of Candida lusitaniae.
Four methods for the accurate delineation of epidemiologically related and unrelated strains of Candida lusitaniae were compared. Three pulsed-field electrophoretic methods, including two contour-clamped homogeneous field gel electrophoresis methods (EKP-1 and EKP-2) yielding electrophoretic karyotype patterns of intact chromosomal DNA and a method in which the chromosomal DNA was macrodigested with the endonuclease SfiI prior to pulsed-field electrophoresis (MDP), and a random amplified polymorphic DNA (RAPD) assay were evaluated. A selected panel of 21 well-characterized isolated representing 13 strains of C. lusitaniae, including 7 epidemiologically related isolates of one strain (group I-A), 3 epidemiologically related isolates of another strain (group I-B), and 11 epidemiologically unrelated isolates (group II), were tested. All isolates were coded and tested in a blinded manner. All seven group I-A isolates were confirmed to be a single strain by the EKP-1 and MDP methods, and the three group I-B isolates were shown to be a single strain by the EKP-1, EKP-2, MDP, and RAPD methods. Subtle differences were noted with two of the group I-A isolates by the EKP-2 method, whereas three of these isolates were different by the RAPD method. Each group II isolate had distinct patterns by all four methods. These data support the fact that the three pulsed-field electrophoretic methods and the RAPD method can be used to delineate strains of C. lusitaniae. The EKP-1, EKP-2, and MDP gave results that correlated with the epidemiologic characteristics of the isolates tested in the study, whereas the RAPD method was perhaps too sensitive in detecting DNA changes for epidemiologic studies.
Development of pulmonary infection in mice inoculated with Blastomyces dermatitidis conidia.
Intratracheal injection of Balb/cByJ mice with 10(4) Blastomyces dermatitidis conida produces chronic pulmonary and disseminated blastomycosis characterized by pyogranulomatous inflammation. To study the evolution of the pulmonary infection, mice were killed at varying intervals after inoculation, their lungs cultured and examined histologically. Nodular intraalveolar infiltrates of macrophages (M phi) were seen on Day 1 with occasional admixed polymorphonuclear leukocytes (PMN). Phagocytized yeast forms within M phi were evident by Day 5. By Day 28 pyogranulomas, which developed first as central microabscesses associated with a peripheral zone of M phi and giant cells containing internalized yeast, were a prominent feature of the infection. Lymphocytic and plasmacytic infiltrates, accumulating next to granulomas, formed the major peripheral component of the granuloma by Day 35. Formation of pyogranulomas was coincident with the host's failure to contain fungal growth measured by the sharp rise in colony-forming units recovered from lungs. Antibody against B. dermatitidis was first detected at Day 35 by enzyme immunoassay, but not until Day 63 by double immunodiffusion. During the 4 wk after inoculation, pulmonary lavage fluid contained > 90% M phi and < 3% PMN. On day 28, PMN rose to 17%, reaching 40% on Day 42. These data contribute to our knowledge of this model and help form the basis for investigations into the roles of fungal pathogenic and host defense mechanisms in blastomycosis.
Interleukin-1 is linked to the respiratory epithelial cytopathology of pertussis.
Bordetella pertussis, the causative agent of whooping cough, releases a muramyl peptide known as tracheal cytotoxin (TCT) that is responsible for destruction of ciliated epithelial cells lining the large airways. In vitro, TCT has been shown to cause this specific pathology in human or hamster respiratory epithelium and to inhibit the proliferation of cultured hamster trachea epithelial cells. The diverse biological actions of muramyl peptides, including adjuvanticity, somnogenicity, and pyrogenicity, have been correlated with the production and release of the inflammatory mediator interleukin-1 (IL-1). Consistent with its ability to reproduce other muramyl peptide actions, recombinant IL-1 caused TCT-like damage to the respiratory epithelium. In the nanogram-per-milliliter range, exogenous IL-1 inhibited DNA synthesis in hamster trachea epithelial cells and reproduced the pathology of TCT in hamster tracheal organ culture. Tumor necrosis factor alpha and IL-6, cytokines also associated with inflammation, were unable to reproduce TCT cytopathology. Furthermore, exposure of respiratory epithelial cells to TCT stimulated production of cell-associated IL-1 alpha, which could be detected within 2 h of TCT treatment. In contrast, there was no evidence of TCT-triggered release of IL-1. Previous studies have suggested that intracellular IL-1 alpha, as well as exogenous IL-1 alpha and IL-1 beta, can inhibit cell proliferation. Our results therefore implicate IL-1 alpha, produced by epithelial cells in response to TCT, as a potential intracellular mediator of the primary respiratory cytopathology of pertussis.
IL-1-induced murine osteoblast IL-6 production is mediated by the type 1 IL-1 receptor and is increased by 1,25 dihydroxyvitamin D3.
IL-1-induced osteoblast IL-6 production represents one possible mechanism by which IL-1 augments bone resorption. In this report, we show that the murine osteoblastic cell line (MC3T3-E1) expresses type 1 IL-1 receptors based on 125I-HrIL1 alpha binding, blocked by type 1 IL-1R antibodies (35F5), and analysis of MC3T3 RNA by reverse transcription (RT)-DNA amplification and Northern analysis. MC3T3 cells do not express detectable type 2 IL-1R mRNA by RT-DNA amplification. IL-1 induces (IL-1 ED50, 0.1 pM) IL-6 production through the type 1 IL-1R as 35F5 antibodies block IL-1-stimulated IL-6 production. Vitamin D3 increases IL-1R expression dose- and metabolite-dependently, with 1,25-(OH)2D3 having the greatest potency, and also enhances IL-1's capacity to stimulate IL-6 production at low IL-1 levels. Both IL-1 and 1,25-(OH)2D3 induce type 1 IL-1R and not type 2 IL-1R upregulation based on ligand binding and RT-DNA amplification. Increased IL-1R expression requires a 5-7-h treatment and is protein/RNA synthesis dependent. These observations imply that IL-1-induced IL-6 production in osteoblasts is mediated by type 1 IL-1Rs and that increased IL-1R expression could play a role in mediating IL-1-induced skeletal responses.
Updated care guidelines for patients with automatic implantable cardioverter defibrillators.
Since its clinical introduction, AICD therapy has gained significant acceptance. Some physicians consider it the "gold standard" in treating malignant tachyarrhythmias associated with sudden cardiac death. As the technology and therapy application have grown, nursing responsibilities have evolved as well. And, with the forthcoming combinations of technology such as AICDs with antitachycardia pacing and bradycardia pacing, the sophistication of the therapy is expected to increase. However, the most critical role for nurses in AICD patient care remains education. Increased utilization has made AICD implants more common, but many patients still lack the initial information and acceptance needed for therapeutic success. Health-care professionals who continue to update and share their understanding of this life-saving technology make invaluable contributions to the care of these patients who have received a second chance at life.
Renal mucormycosis: a case report and review of the literature.
A 64-year-old man presented with acute renal failure secondary to renal mucormycosis. The pathological findings are described and the literature is reviewed.
Sensing aberration by the automatic implantable cardioverter defibrillator during intraoperative testing.
A 50-year-old man underwent replacement of his automatic implantable cardioverter defibrillator (AICD) because a magnet test revealed severe battery depletion. He had had his unit implanted 18 months previously after an episode of sudden cardiac death. He had documented torsades de pointes and inducible ventricular tachycardia, confirmed by electrophysiologic study. Before a new unit was implanted thresholds were measured by an external cardioverter defibrillator. Ventricular fibrillation (VF) was induced by alternating current through a standard, line-operated battery charger with stimulation delivered to the epicardium via rate-sensing electrodes. VF was allowed to continue for 10 seconds before shock was delivered. Termination of VF required 15 joules, which was higher than that required at initial implantation 18 months earlier. The new pulse generator was activated for testing and VF was again induced. The AICD discharged after 12.3 seconds. Prior to wound closing, the AICD was deactivated by magnet. Instead of R-wave synchronous beeping tones during deactivation, double beeping tones were heard. Electrogram recordings revealed abnormalities of the T-wave and ST segment of the rate-sensing electrodes, which were the cause of the tone irregularities. Stabilization of the T-wave and ST segment occurred within 8 minutes and the tones became normal. The procedure was then completed.
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.
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.
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.
Get ready. The new antiarrhythmics are coming.
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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.
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.
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.
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.