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Biomedical subjects

H Hahn

Publications and source records attributed to H Hahn.

At least 19 recordsLinked to original sources

Kinetic analysis of cytokine gene expression in the livers of naive and immune mice infected with Listeria monocytogenes. The immediate early phase in innate resistance and acquired immunity.

The anamnestic response to infection with Listeria monocytogenes is characterized by the rapid elimination of normally lethal doses of bacteria and accelerated granuloma formation. These phenomena are mediated by listeria-specific memory T cells within the first 24 h after reinfection. In order to elucidate the mechanisms operative during this decisive phase of infection, we conducted a comprehensive kinetic and quantitative analysis of cytokine gene expression in the livers of naive and immune mice. Organs were removed at 30 min, and 1, 2, 6, and 24 h after primary and secondary infections, and PCR3-assisted messenger RNA (mRNA) amplification was performed on matched samples using primers specific for IL-1 beta, IL-6, M-CSF, GM-CSF, TNF-alpha, IFN-gamma, IL-10, IL-4, IL-2, IL-3 and I1-2Rp55. The cytokine pattern characteristic of secondarily infected animals differed qualitatively by the expression of mRNA for IL-2, IL-2Rp55, IL-3, and IL-4, demonstrating the accumulation and activation of specific T cells in the livers as early as 1 to 2 h after reinfection. Combined in vivo depletion of both CD4+ and CD8+ T cells before reinfection almost completely abrogated the differentiated cytokine profile typical of the anamnestic response. Using competitive PCR for semiquantitative determination of mRNA levels, the amount of IL-1 beta and IL-6 mRNA was found to be very similar during primary and secondary infection, whereas TNF-alpha mRNA was found to be increased by approximately 10-fold 2 h and IFN-gamma mRNA by approximately 50 to 100-fold 6 h after reinfection when compared with a primary challenge. Combined in vivo depletion of both CD4+ and CD8+ T cells before reinfection resulted in a substantial (approximately 10-fold) decrease in IFN-gamma mRNA expression. To correlate these findings with cytokine secretion, spleen cells from naive and immune as well as normal and CD4+ and CD8+ cell depleted mice infected 6 h previously were cultured for 48 h, and supernatants were analyzed for the amount of the above mentioned cytokines. Semiquantitative PCR-assisted mRNA amplification is demonstrated to be a superior tool in dissociating the mediators of innate resistance from those operative in protective immunity and granuloma formation.

Animals

Head-upright tilt-table testing in evaluation and management of the malignant vasovagal syndrome.

Vasovagally mediated cardiac asystole has been proposed as a potential cause of sudden cardiac death. To assess this possibility and identify characteristics that define patients with vasovagally mediated asystole, head-upright tilt-table testing was performed in 50 consecutive patients (26 women and 24 men, mean age 42 +/- 10 years) with recurrent unexplained syncope. The upright tilt-table test was performed in the fasting state for 30 minutes, with or without the use of intravenous isoproterenol (1 to 3 micrograms/min). The production of ventricular asystole lasting greater than 4 seconds was considered a positive result. All patients with tilt-induced asystole received therapy with either beta blockers, disopyramide, transdermal scopolamine or atrioventricular permanent pacing, the efficacy of which was evaluated with serial tilt-table tests. Reproducible tilt-induced asystole occurred in 10 patients (7 men and 3 women, mean age 23 +/- 12 years) (7 patients during baseline tilt, and 3 during isoproterenol infusion). Analysis of this group revealed that they had significantly more frequent and severe syncopal episodes (3 patients had episodes needing bystander cardiopulmonary resuscitation) than did those patients with tilt-induced syncope without asystole. All patients who had tilt-induced asystole eventually became tilt-table negative with therapy (4 with beta blockers, 2 with disopyramide, and 4 with atrioventricular permanent pacing), and over a mean follow-up of 21 +/- 6 months no further syncopal episodes occurred. It is concluded that patients with recurrent tilt-induced asystole represent a distinct subgroup that has recurrent severe syncope that may mimic or result in sudden cardiac death. Thus, the predischarge electrophysiologic study could predict late outcome with recurrence of preexicitation or supraventricular tachycardia in patients who had undergone surgical ablation of the accessory pathway with an overall predictive accuracy of 95% (107 of 113 patients), negative predictive value of 96% (103 of 107), and positive predictive value of 67% (4 of 6).

Adolescent

Comparative activity of the topical quinolone OPC-7251 against bacteria associated with acne vulgaris.

The antibacterial activity of the topical quinolone OPC-7251 against bacteria commonly found in acne vulgaris was tested in vitro by an agar dilution method. The MIC50 was 0.25 mg/l for Propionibacterium acnes, 0.125 mg/l for Propionibacterium granulosum, 0.03 mg/l for Staphylococcus aureus and 0.06 mg/l for coagulase-negative staphylococci. Compared with seven other antibiotics tested (ciprofloxacin, penicillin, erythromycin, tetracycline, clindamycin, fusidic acid and gentamicin), OPC-7251 had potent activity against both propionibacteria and staphylococci and the lowest incidence of resistant strains.

Acne Vulgaris

Protective immunity and granulomatous inflammation is mediated in vivo by T cells reactive to epitopes common to avirulent and listeriolysin-negative mutants of Listeria monocytogenes.

The ability of several listeriolysin O-negative mutants of the EGD and NCTC 7973 strains of Listeria monocytogenes to activate specific T cell responses in vitro and in vivo was determined. T cell lines from different inbred mouse strains and derived T cell clones elicited by L. monocytogenes, strain EGD, which are able to adoptively transfer protection and granuloma formation were examined. Specificity testing revealed no differences between listeriolysin-positive and -negative strains to induce proliferation of the T cell lines and clones. Similar results were obtained when we examined CD4+ T cell-mediated granuloma formation in the livers of mice previously immunized with viable bacteria of the virulent strain. Granulomatous inflammation could be elicited by iv application of heat-killed bacteria of listeriolysin-positive and of -negative bacteria. Protective immunity to listerial infections and granulomatous inflammation therefore appears to be mediated by T cells recognizing epitopes on listerial antigens that are shared by both pathogenic and nonpathogenic Listeria strains.

Animals

The use of external, noninvasive pacing for the termination of ventricular tachycardia in the emergency department setting.

STUDY OBJECTIVE: To determine the potential usefulness of external cardiac pacing for the termination of sustained ventricular tachycardia in the emergency department setting. TYPE OF PARTICIPANTS: Five men and one woman (mean age, 57 years) who presented to the ED with a wide-complex, hemodynamically stable tachycardia that was later proven to be ventricular in origin. INTERVENTION: Each patient underwent external overdrive pacing using a modified external pacemaker at a pulse amplitude of 120 mA and a rate of 200 pulses per minute. RESULTS: In all six patients, external cardiac pacing was able to successfully terminate tachycardia without complication. CONCLUSION: We conclude that external noninvasive pacing may be an effective means of terminating ventricular tachycardia in the ED setting.

Adult

Delayed type hypersensitivity (DTH): quantitative studies of mycobacteria-induced destructive and non-destructive DTH-reactions in the skin of guinea pigs.

Research on delayed type hypersensitivity (DTH) to facultative intracellular bacteria in guinea pigs focused especially on intracutaneous DTH reactions. However, phenomena of erythematous and necrotic skin reactions were only evaluated qualitatively, dose-response relationships not investigated, differences between early and late reactions overlooked and the development of unspecific skin necrosis ignored. In this work, these aspects were investigated by characterisation of DTH-mediated reactions against mycobacterial antigens in the skin of guinea pigs. Intracutaneous injection of mycobacterial antigen into the skin of immunised and non-immunised guinea pigs induced an erythematous reaction which reached its peak after 24 h. On days two and three after challenge, the centre of the erythema blanched and necrotised. During the next days, skin necrosis increased and reached a peak on days six and seven. In immunised guinea pigs, DTH led to a specific enhancement of erythematous and necrotising skin reactions which also appeared in non-immunised guinea pigs. Thus, an early erythematous and a late necrotising DTH-reaction were identified by their morphology and time course. Both types of DTH-mediated allergy revealed dose-dependency from the intracutaneously injected antigen doses. Erythematous and necrotising DTH reactions against viable and killed mycobacteria showed a similar time course and morphology. DTH reactivity which was induced by immunisation with Mycobacterium tuberculosis showed cross-reactivity with antigens of Mycobacterium bovis.

Animals

Delayed type hypersensitivity (DTH): studies on necrotising DTH-reactions against listerial antigen in the skin of guinea pigs.

Delayed type hypersensitivity (DTH) to facultative intracellular bacteria which leads to destructive skin reactions was so far only investigated against mycobacterial antigens in guinea pigs whereas this work investigates destructive DTH-reactions in the skin of guinea pigs which are directed against listerial antigens. Toxic factors of viable listerias induced an enhancement of destructive skin reactions in non-immunised guinea pigs as compared to immunised ones. In contrast, heat killed listerias (HKL) induced necrotising skin reactions in immunised and non-immunised guinea pigs which were significantly enhanced by DTH in immunised guinea pigs. 5 days after immunisation, necrotising reactivity was maximal and increased in a dose-dependent mode with higher amounts of HKL. Listeria-specific T-cells were able to interact specifically with allogeneic macrophages in vitro. By means of adoptive transfer of listeria-specific T-cells it was possible to transfer successfully Listeria-specific DTH-reactivity from immunised donors to non-immunised recipients.

Animals

Diagnosis, prevalence and drug resistance of mycobacteria in HIV-positive and HIV-negative patients of an urban population in Germany.

In a survey of 3004 clinical specimens from 1112 HIV-negative and 679 clinical specimens from 140 HIV-positive patients which were submitted to our mycobacterial laboratory, we have analysed the different diagnostic approaches concerning mycobacterial disease in these two populations. We have assessed specimen-type, culture result, microscopical diagnosis and prevalence in relation to HIV status. Isolation rates of mycobacteria were highest in blood cultures from HIV-positive patients. 10 out of 140 HIV-positive patients had positive mycobacterial culture results. All 10 had positive blood cultures, but only three of them were positive for M. tuberculosis.

Antitubercular Agents

Recurrent unexplained syncope in the elderly: the use of head-upright tilt table testing in evaluation and management.

OBJECTIVE: To investigate the usefulness of head-upright tilt table testing for vasovagal episodes in the evaluation and management of elderly patients with recurrent idiopathic syncope. DESIGN: Prospective survey. SETTING: Electrophysiology laboratory of a university hospital. PATIENTS: Twenty-five patients (11 male, 14 female; mean age 73 +/- 6 years) with recurrent unexplained syncope and seven control subjects with other causes of syncope (4 male, 3 female; mean age 70 +/- 4 years). METHODS: Each patient underwent head-upright tilt table testing for 30 minutes with or without an infusion of isoproterenol (1-3 micrograms/min given intravenously) in an attempt to provoke bradycardia, hypotension, or both. MAIN RESULTS: Syncope occurred in nine patients (36%) during the baseline tilt and in seven patients (28%) during isoproterenol infusion (total positives 64%). None of the controls had syncope during the test. All of the patients who had positive test results eventually became tilt table negative with therapy, and over a mean follow-up period of 24 months, no further syncopal episodes have occurred. CONCLUSIONS: Head-upright tilt table testing combined with isoproterenol infusion may be a useful tool in the diagnosis of vasovagal syncope in the elderly and in the evaluation of preventive therapy.

Aged

Reproducibility of head upright tilt table test results in patients with syncope.

Head upright tilt table testing is a promising technique for the evaluation and management of vasovagal (neuroregulatory) syncope. In order to determine the day-to-day reproducibility of results using this technique we performed head upright tilt table testing (with or without graded isoproterenol infusion) in 21 patients (12 males, 9 females, mean age 34 +/- 19.1 years). During the first tilt study a total of 14 patients experienced syncope (six during baseline tilt, mean tilt time 15.8 +/- 7 minutes, eight following tilt with graded isoproterenol infusion, mean tilt time 17.7 +/- 9 minutes) while seven were negative. During the second tilt study (performed 3-7 days following the first study) the results of the first study were duplicated in 19 patients (90%) (six during baseline tilt, mean time 17.5 +/- 8 minutes, eight following graded isoproterenol infusion, mean time 15.9 +/- 7 minutes), however the level of provocation required to provoke syncope differed from that needed in the initial test in five patients (24%). We conclude that the results of head upright tilt table testing with graded isoproterenol infusions can be duplicated in 90% of patients, although some day-to-day variability exists in the degree of provocation necessary to elicit a positive response.

Adult

Tachycardia sensing failure of an implantable cardioverter defibrillator in a patient with hypertrophic cardiomyopathy.

A 17-year-old white male was found to have nonobstructive hypertrophic cardiomyopathy after suffering three severe syncopal episodes. He experienced an episode of sustained polymorphic ventricular tachycardia during exercise tolerance testing that required cardioversion. Electrophysiological studies were able to reproduce sustained polymorphic ventricular tachycardia that was unresponsive to standard pharmacotherapy. An automatic implantable defibrillator was placed. However, during implantation with the rate sensing electrodes on the left ventricle, it was found that the extremely polymorphic nature of the tachycardia caused such rapid fluctuations in the sensed R wave signal that the device could not properly detect the tachycardia. This was felt to be due to the automatic gain control circuit of the Ventak 1550. The problem was solved by moving the rate sensing electrodes to the lateral right ventricle. This case suggests that the unique arrhythmic substrate of hypertrophic cardiomyopathy may present sensing difficulties during automatic implantable defibrillator insertion.

Adolescent

The use of head-upright tilt table testing in the evaluation and management of syncope in children and adolescents.

Recurrent syncope in an otherwise healthy child or adolescent is a common anxiety provoking disorder. Vasovagally mediated hypotension and bradycardia are believed common, yet difficult to diagnose, causes of syncope in this age group. Upright tilt table testing has been suggested as a potential method to test for vasovagal episodes. This study evaluated the utility of this technique in the evaluation and management of recurrent syncope in children and adolescents. Thirty patients with recurrent unexplained syncope were evaluated by use of an upright tilt table test for 30 minutes, with or without an infusion of isoproterenol (1 to 3 micrograms/min given intravenously), in an attempt to produce hypotension, bradycardia, or both. There were 15 males and 15 females, mean age 14 +/- 6 years. Each of the tilt positive patients received therapy with either fluorohydrocortisone, beta blockers, or transdermal scopolamine. Syncope occurred in six patients (20%) during the base line tilt and in 15 patients (50%) during isoproterenol infusion (total positives 70%). All initially positive patients were rendered tilt negative by therapy. Over a mean follow-up period of 20 months, no further episodes have occurred. We conclude that tilt table testing is a useful and effective test in the evaluation of unexplained syncope in childhood.

Adolescent

Protective immunity and granuloma formation are mediated by two distinct tumor necrosis factor alpha- and gamma interferon-dependent T cell-phagocyte interactions in murine listeriosis: dissociation on the basis of phagocyte adhesion mechanisms.

Listeria-immune mice are able to express protective immunity in the absence of CD4+ T cells and an apparent granulomatous inflammation. Using a monoclonal antibody (5C6) able to inhibit the recruitment of myelomonocytic cells into inflammatory foci by binding to complement receptor type 3 (CR3/CD11b), we could show that protective immunity and granuloma formation indeed depend on two distinct types of T cell-phagocyte interactions. Listeria-specific CD8+ T lymphocytes, possibly in collaboration with CD4- CD8- T cells, rapidly interact with myelomonocytic cells infiltrating infected tissues in a CR3/CD11b-dependent manner. This interaction results in potent antilisterial protection but not in granuloma formation. On the contrary, CD4+ T cells are able to induce adhesion mechanisms that allow the accumulation of monocytes in granulomatous lesions even in the presence of monoclonal antibody 5C6. However, the protective capacity of these CR3/CD11b-independent T cell-mediated immune mechanisms is low in listeriosis. Tumor necrosis factor alpha and gamma interferon, known to be essential for the expression of both resistance and acquired immunity, are shown to be necessarily involved in granuloma formation, too. It therefore remains to be explained why CD8+ T cells, able to secrete both cytokines, do not induce granuloma formation. The data point to the presence of an as yet undefined CD4+ T cell-derived granuloma-inducing factor and favor the hypothesis that CD8+ T cells, in collaboration with circulating phagocytes, mediate immunity by rapidly liberating listeriae from permissive cells or protecting them from becoming infected.

Animals

Head-upright tilt-table testing: a useful tool in the evaluation and management of recurrent vertigo of unknown origin associated with near-syncope or syncope.

Recurrent idiopathic vertigo associated with near-syncope and syncope is a common perplexing problem, some cases of which are considered autonomically mediated (vasovagal). Upright-tilt-table testing has emerged as a potential method to test for vasovagal episodes. This study evaluated the use of this technique in the evaluation and management of patients with recurrent idiopathic vertigo associated with near-syncope or syncope. Twenty-one patients with recurrent unexplained vertigo and syncope/near-syncope and 11 control subjects were evaluated by use of an upright-tilt-table test for 30 minutes, with or without a graded isoproterenol infusion (1 to 4 micrograms/min given intravenously), in an attempt to provoke hypotension, bradycardia, or both, which reproduced the patient's symptoms. The patients included 10 men and 11 women (mean age, 51 +/- 16 years). Eleven controls with no history of vertigo were also studied. Transcranial Doppler sonography was used to assess cerebral arteriolar blood flow during tilt. All tilt-positive patients were placed on therapy with either beta-blockers, disopyramide, or transdermal scopolamine, the effectiveness of which was determined with another tilt-table study. Symptoms occurred in seven patients (33%) during the baseline tilt and in eight patients (38%) during isoproterenol infusion (total positives, 71%). Transcranial Doppler sonography demonstrated a 225% +/- 192% increase in pulsatility index and a 70% +/- 29% increase in resistance index (indicative of cerebral arteriolar vasoconstriction) at the time of vertigo. No control subject experienced syncope during this test. Each tilt-positive patient eventually became tilt-negative with therapy, and over a mean follow-up period of 26 months, no further episodes have occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Spontaneous pulsatile growth hormone release in male and female premature infants.

Although premature infants have high umbilical cord GH levels, little is known about spontaneous GH release in these individuals. The purpose of our study was to investigate spontaneous 12-h GH release in appropriate for gestational age male and female premature infants. We studied 22 premature infants (15 males and 7 females) of appropriate length and weight for age. Gestational ages, birth weights, birth lengths, and ages at the time of study were similar in male or female infants. All infants were biochemically euthyroid. Blood was taken every 30 min over a 12-h period from an indwelling umbilical catheter; no stress occurred during the blood withdrawal. GH was determined by a double antibody RIA, using 0.01 mL plasma. GH pulse detection was undertaken using Cluster, a computerized pulse detection algorithm. Total insulin-like growth factor-I and -II (IGF-I and -II) levels were measured after separation of the IGFs from the serum binding proteins. Spontaneous pulsatile GH release was observed in all infants studied. No differences were found between males and females in the pulse characteristics of frequency, maximal amplitude, incremental amplitude, width, or area. The GH pulse frequency per 12 h was 3.2 +/- 0.3 (mean +/- SE) in males and 3.0 +/- 0.7 in females. The maximal pulse amplitude was 50.7 +/- 6.2 micrograms/L in males and 44.7 +/- 9.0 micrograms/L in females. The incremental pulse amplitude was 24.3 +/- 3.2 micrograms/L in males and 20.2 +/- 3.9 micrograms/L in females. The mean 12-h GH level was 37.1 +/- 4.8 micrograms/L in males and 35.8 +/- 8.5 micrograms/L in females; the average GH nadir was 26.1 +/- 4.0 micrograms/L in males and 24.4 +/- 8.3 micrograms/L in females. Both IGF-I and IGF-II concentrations were similar in males and females. The mean IGF-I levels were 10.7 +/- 1.5 ng/mL in males and 7.5 +/- 1.1 ng/mL in females; IGF-II levels were 96.0 +/- 12.0 ng/mL in males and 115.4 +/- 17.1 ng/mL in females. These results demonstrate similar pulsatile GH release in male and female premature infants at a mean age of 32-33 weeks. Compared with previously reported values for mean GH concentration and average GH nadir in older children, the values in these premature infants were much higher. We speculate that the higher GH levels in premature infants may result from decreased negative feedback associated with low IGF-I levels. The premature infant's somatotrophs may also not fully respond to the GH inhibitory action of somatostatin.

Blood Glucose

Differentiation of convulsive syncope and epilepsy with head-up tilt testing.

OBJECTIVE: To evaluate the usefulness of head-upright tilt table testing in the differential diagnosis of convulsive syncope from epileptic seizures in patients with recurrent idiopathic seizure-like episodes. DESIGN: Prospective, nonrandomized study. SETTING: Electrophysiology laboratory of a university hospital. PATIENTS: Fifteen patients (8 men and 7 women patients; mean age, 29 +/- 20 years) with recurrent unexplained seizure-like episodes, unresponsive to antiseizure medication. MEASUREMENTS: Head-upright tilt table testing with or without isoproterenol infusion. Five patients who were initially tilt positive had a second tilt test with continuous electroencephalographic (EEG) recording. MAIN RESULTS: Syncope associated with tonic-clonic seizure-like activity occurred in six patients (40%) during the baseline tilt and in four patients (27%) during isoproterenol infusion (total positive tests, 67%). The EEG showed diffuse brain wave slowing (not typical of epileptic seizures) in five of five patients during the convulsive episode. All patients who had positive test results eventually become tilt table negative after therapy, and over a mean follow-up period of 21 +/- 2 months, no further seizure-like episodes have occurred. CONCLUSION: Upright tilt table testing combined with isoproterenol infusion may be useful to distinguish convulsive syncope from epileptic seizures.

Adolescent

Utility of upright tilt-table testing in the evaluation and management of syncope of unknown origin.

PURPOSE: Vasovagally mediated hypotension and bradycardia are believed to be common, but difficult to diagnose, causes of syncope. Upright tilt-table testing has been proposed as a possible way to test for vasovagal episodes. This study investigated the clinical utility of this technique in the evaluation and management of patients with syncope of unknown origin. PATIENTS AND METHODS: Twenty-five patients with recurrent unexplained syncope and six control subjects were evaluated by use of an upright tilt-table test for 30 minutes, with or without an infusion of isoproterenol (1 to 3 micrograms/minute given intravenously), in an attempt to provoke bradycardia, hypotension, or both. Of the 25 patients, there were 14 males and 11 females, with a mean age of 50 +/- 16 years. Six control patients with no history of syncope were also studied. All tilt-positive patients received therapy with either beta-blockers, disopyramide, transdermal scopolamine, or hydroflurocortisone, the efficacy of which was evaluated by another tilt-table test. RESULTS: Syncope occurred in six patients (24%) during the baseline tilt and in nine patients (36%) during isoproterenol infusion (total positives, 60%). None of the controls had syncope during the test. All patients who had positive test results eventually became tilt-table-negative by therapy, and over a mean follow-up period of 16 +/- 2 months no further episodes have occurred. CONCLUSION: From this study we conclude that upright tilt-table testing combined with isoproterenol infusion is clinically useful in the diagnosis of vasovagal syncope and the evaluation of pharmacologic therapy.

Adolescent