Safety and efficacy of liposomal amphotericin B in treating AIDS-associated disseminated cryptococcosis.
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Biomedical subjects
Publications and source records attributed to H Hahn.
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To determine what effect chronic implantation of automatic implantable cardioverter defibrillator epicardial patch electrodes had on initial high defibrillation thresholds at implant, six patients were studied. There were five men, one woman, mean age 61 years. Three had coronary artery disease and three had dilated cardiomyopathies. Mean ejection fraction was 20%. Two patients underwent concomitant coronary artery revascularization and one underwent mitral valve replacement. No patient was on antiarrhythmic drugs. At the time of initial implant, adequate defibrillating thresholds could not be obtained in any patch configuration despite the use of up to 40 joules. Further testing was precluded in each patient due to the development of profound hypotension (less than or equal to 70 mmHg systolic) that was poorly responsive to pressors. The patch electrodes were then implanted in an arbitrary anterior-posterior position and the leads were tunneled to an abdominal pocket. After 10-15 days (mean 11), the lead ends were exposed and defibrillation testing was performed again. In all six patients, adequate defibrillation thresholds were obtained (mean 18 joules). We conclude that if adequate defibrillation thresholds cannot be obtained at implant and if further testing cannot be performed without jeopardizing the life of the patient, the patch electrodes should be implanted and retesting performed at 10-15 days.
In the present study we attempted to analyze the possibility to induce in mice a T-cell response using killed Listeria monocytogenes in adjuvant. Clearly, nonviable antigen is capable of inducing protective and granuloma-forming T cells in C57BL/6 mice when emulsified in complete Freund's adjuvant. These T cells were cloned in vitro by using antigen and irradiated splenocytes, as antigen-presenting cells, and the clones were characterized in vivo. Listeria-specific T-cell clones showed protective and chemotactic activity upon adoptive transfer, although some degree of functional heterogeneity among different clones was observed. The heterogeneous in vivo functions could not be correlated with the ability of the clones to produce gamma interferon or T-cell growth factor (interleukin-2 and/or interleukin-4). It was demonstrated that an in vivo relevant fraction of listeria-specific T lymphocytes can be induced by nonviable antigen in complete Freund's adjuvant. These results show that the low immunogenicity of heat-killed bacteria is not due to the expression of specific protective T-cell epitopes only by live bacteria.
The role of phagocytes and the complement system as potential host defense mechanisms against bacterial infection were studied in mice with two isogenic strains of Yersinia enterocolitica serotype O8 differing in pathogenicity because of differences in plasmid content. Complement depletion in mice by intraperitoneal injection of cobra venom factor did not affect the course of colonization of the intestinal tissue by each strain, indicating that in mice complement is not essential for the elimination of these bacteria. This conclusion is supported by the fact that fresh murine serum had no bactericidal effect in vitro either on the pathogenic or on the nonpathogenic strain. However, in the intestinal tissue as well as in the peritoneal cavity, only the pathogenic, plasmid-bearing Y. enterocolitica strain survived, while the nonpathogenic, plasmidless strain was rapidly eliminated. Since elimination from the peritoneal cavity is due to phagocytosis by polymorphonuclear leukocytes and macrophages, resistance to phagocytosis in vivo seems to be the decisive factor determining the virulence of pathogenic Y. enterocolitica strains.
BACKGROUND: To determine the effect of vasovagally mediated syncope on the cerebral circulation, transcranial Doppler sonography was used to assess changes in cerebral blood flow velocity during head-upright tilt-induced syncope. METHODS AND RESULTS: Thirty patients (17 men and 13 women; mean age, 43 +/- 22 years) with recurrent unexplained syncope were evaluated by use of an upright tilt-table test for 30 minutes, with or without an infusion of intravenous isoproterenol (1-4 micrograms/min), in an attempt to provoke bradycardia, hypotension, or both. Transcranial Doppler sonography was used to assess middle cerebral artery systolic velocity (Vs), diastolic velocity (Vd), ratio of systolic to diastolic velocities, pulsatility index (PI = Vs-Vd/Vmean), and resistance index (RI = Vs-Vd/Vs) before, during, and after tilt. Syncope occurred in six patients (20%) during the baseline tilt and 14 (46%) during isoproterenol infusion (total positives, 66%). In the tilt-positive patients, concomitant with the development of hypotension and bradycardia, transcranial Doppler sonography showed a 75 +/- 17% decrease in diastolic velocity, unchanged systolic velocity, a 46 +/- 17% decrease in mean velocity, a 295 +/- 227% increase in pulsatility index, and a 73 +/- 34% increase in resistance index. CONCLUSIONS: These findings reflect increased cerebrovascular resistance secondary to arteriolar vasoconstriction distal to the insonation point of the middle cerebral artery. This is paradoxic because the expected response of the cerebral circulation to hypotension is vasodilation. We conclude that abnormal baroreceptor responses triggered during vasovagal syncope result in a derangement of cerebral autoregulation with paradoxic vasoconstriction in the face of increasing hypotension.
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L-[4,5-3H]isoleucine was introduced to label anteiso-fatty acid (AIFA)-containing lipids in Staphylococcus aureus SG 511. After an overnight incubation in peptone broth in the presence of 37 kBq L-[4,5-3H]isoleucine/ml, 8.5-13% of the total radioactivity applied was found to be incorporated into the cells. 22.4-25.6% of the incorporated radioactivity was found in AIFA-containing lipids extracted by chloroform-methanol-water (2:1:0.2, v/v/v) at pH 2. The interphase contained 70-75% of the incorporated radioactivity. Lipoteichoic acid, extracted by phenol-water (80:20, w/v) contained less than 1% of the incorporated radioactivity, as measured after purification by hydrophobic interaction chromatography on octyl sepharose gel. Within 1 h after addition of 10 micrograms/ml penicillin G to exponentially growing cultures of S. aureus, that led to non-lytic death of the cells, 11.9-18.1% of the incorporated L-[4,5-3H]isoleucine label were released. Lipids containing AIFA were excreted to 5.4-8.4% of total incorporated activity; this amount represents more than 1/4 of the labeled cellular lipids.
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Cardiac pacing from either endocardial or transesophageal sites has proven useful in termination of sustained supraventricular tachycardia in children. In two patients we demonstrated the efficacy of external pacing in the termination of sustained supraventricular tachycardia. The ease and apparent safety of the technique make it an attractive addition to our current therapies for supraventricular tachycardia in children. The usefulness of external pacing in treating pediatric arrhythmias needs further evaluation.
Cervical and vaginal carriage of group B streptococci (GBS) is normally associated with an appropriate immune response confining these organisms to a commensal state in this human habitat. A newly developed indirect enzyme-linked immunosorbent assay compares the antibody responses against two antigen preparations of GBS-serotypes Ia, Ib, II and III in the cord sera of cervico-vaginal GBS-carriers and non-carriers during pregnancy. Antibody responses in GBS-positive women against both antigen preparations were found to be significantly higher than in GBS-negative women (p less than 0.005). Antibody levels towards the EDTA-antigen were markedly lower than levels for the HCl-antigen thus indicating two different antibody responses.
A combination of clindamycin and colloidal bismuth subcitrate was evaluated for synergistic inhibition of Helicobacter pylori employing the agar dilution method. A total of 47 clinical isolates of Helicobacter pylori were examined. Synergistic interaction was observed in 36%, additive behaviour in 64% of the strains. No antagonism could be detected.
The minimum inhibitory concentrations of three bismuth subcarbonate preparations: 1. bismuth subcarbonate, 2. a mixture of 50% bismuth subcarbonate and 50% citric acid, 3. a mixture of 50% bismuth subcarbonate and 50% potassium citrate were assayed against 30 strains of Campylobacter pylori employing the agar dilution method. Bismuth subcarbonate alone exhibited an MIC50 of 2 mg/l and was more effective than the two combinations (MIC50 4 mg/l). It is concluded that the addition of citrate ions does not improve antibacterial activity.
Bacteroides species and Enterobacteriaceae are known to cause synergistic infections. However, the mechanisms behind this synergy are not completely understood. Several authors have shown that Bacteroides species may inhibit the phagocytosis of Enterobacteriaceae by polymorphonuclear leukocytes as well as by macrophages. With the present study we have addressed the question of whether Bacteroides fragilis (BF) is also capable of suppressing specific immune functions. When incubated together with murine lymphocytes, BF significantly inhibited the blastogenic transformation of these cells stimulated by Escherichia coli-lipopolysaccharide (LPS) or concanavalin A. This effect was dose dependent and was not mediated by prostaglandins. Other bacteria such as E. coli or Listeria monocytogenes did not show such an extensive suppression, while Streptococcus pneumoniae was equally active. BF also inhibited the pokeweed mitogen induced blastogenic transformation of human lymphocytes. Moreover, lymphocytes from BF-injected animals obtained 3 to 12 hours after infection proved to be partly refractory for LPS-stimulation. Finally, BF injections also affected T-cell dependent immunity as judged from the aggravation of an experimental listeriosis in mice.
In order to evaluate the potential use of external cardiac pacing (EXP) in the clinical termination of sustained ventricular tachycardia (VT), we attempted VT terminations in seven patients. All had recurrent sustained monomorphic ventricular tachycardia (mean rate 145 beats/min), which had previously required cardioversion. During subsequent VT episodes, all seven underwent overdrive pacing with EXP at a pulse amplitude of 120 mA, and rates of 200 pulses/min. A total of 18 of 18 episodes of VT were successfully terminated by EXP alone. In one patient, the first attempt at EXP termination of one episode of VT resulted in an acceleration of the tachycardia, which was then terminated by EXP. All patients tolerated EXP well with minimal sedation. We conclude that EXP may be an effective clinical modality for the termination of sustained monomorphic ventricular tachycardia.
Recent evidence indicates that ileal Peyer's patches represent the main infection route for Yersinia enterocolitica. In this study transmission and scanning electron microscopy have shown that only a small fraction of bacteria present in the lumen adhere to the follicle-associated murine epithelium with no discernible preference for either M or absorptive cells. Yersiniae attached to M cells are phagocytosed and transported from the lumen into the lamina propria. No invasion of columnar absorptive cells was observed. These data, in combination with recently published reports, indicate that the involvement of M cells is a common step in bacterial invasion of Peyer's patches.