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Biomedical subjects

A Hahn

Publications and source records attributed to A Hahn.

At least 55 records · Page 3Linked to original sources

Failure of ganciclovir prophylaxis to completely eradicate CMV disease in renal transplant recipients treated with intense anti-rejection immunotherapy.

Ganciclovir prophylactic regimens have been shown to be effective in renal transplant recipients at risk for primary (donor seropositive/recipient seronegative) and secondary (recipient seropositive) cytomegalovirus (CMV) disease. However, in addition to serologic factors, the type and intensity of the administered immunosuppression is a strong risk factor for CMV disease. Since January 1995, we have utilized a potent immunosuppressive protocol selectively in recipients at high risk for immunologic graft loss, defined as retransplant recipients, recipients with delayed graft function, non-Caucasian recipients, and recipients suffering from acute rejection. Between January 1995 and December 1996, 110 consecutive renal transplants were performed in recipients who were either CMV seropositive or received an allograft from a CMV-seropositive donor. All recipients received ganciclovir prophylactic therapy for 3 months post-transplant. Group I (N = 43) consisted of recipients at high-immunologic risk for graft loss as defined above. These recipients were treated with an intense anti-rejection immunotherapeutic regimen consisting of Cellcept, Neoral, and prednisone, with the frequent addition of antilymphocyte antibody therapies and intravenous methylprednisolone. The remaining 67 recipients (group II) were treated with a less intense immunotherapeutic regimen consisting of azathioprine, Neoral, and prednisone. The incidence and severity of CMV disease and the patient and allograft survival were compared. The incidence of CMV syndrome was greater in group I (28%) compared with group II (7%), and was statistically significant (p < 0.05). The 1-yr patient and graft survival were similar, 95 and 91%, respectively, for group I compared with 97 and 97%, respectively, for group II. These data suggest that 3 months of ganciclovir prophylactic therapy is significantly less effective for the prevention of CMV disease in renal transplant recipients at high risk for acute rejection treated with an intense immunotherapeutic regimen. These data suggest that more effective prevention of CMV disease in these high-risk recipients will require the addition of other anti-viral agents, such as immunoglobulin preparation to the prophylactic regimen.

Adult↗

Randomized controlled trial of brain-derived neurotrophic factor in Guillain-Barré syndrome: a pilot study.

Brain-derived neurotrophic factor (BDNF) has the theoretical potential to protect neurones from axonal degeneration. The objective of this study was to discover whether brain-derived neurotrophic factor is safe in Guillain-Barré syndrome, and to make preliminary observations of its efficacy. This was a parallel group randomized controlled trial of subcutaneous brain-derived neurotrophic factor 25 microg/kg daily compared with placebo for up to 24 weeks or until patients could walk without aid. Six patients received brain-derived neurotrophic factor, of whom three had serious adverse events including one death. Four patients received placebo, of whom two had serious adverse events including one death. The rate and extent of recovery were similar in the two groups. This pilot study did not detect any serious adverse events attributed to brain-derived neurotrophic factor treatment.

Adolescent↗

Methicillin-resistant Staphylococcus aureus in a teaching hospital: investigation of nosocomial transmission using a matched case-control study.

In early 1996 a hospital-wide methicillin-resistant Staphylococcus aureus (MRSA) epidemic was recognized in a 900-bed university hospital. In order to investigate hospital-specific transmission routes, a case-control study was carried out. Cases and controls were matched for age (+/- 10 years), sex, admission date (+/- 10 days) and clinical department on admission. Data on potential risk factors, were retrieved by chart review. Between June 1996 and February 1997, 67 patients with hospital-acquired MRSA were identified. Molecular typing showed that 85% of the cases carried an indistinguishable strain. The average time at risk for cases and controls was 17.3 and 23.7 days, respectively (P= 0.01). Seventeen patients (25.4%) developed infection. Conditional multivariate regression analysis showed that intensity of care (P= 0.002), number of transfers (P= 0.019), and fluoroquinolone therapy (P= 0.025) were independently associated with acquisition of MRSA. Intensity of care can be considered as a surrogate marker for a number of manipulations which represent the main risk factors for MRSA transmission. Frequent transfers within the hospital hinder, not only the epidemiological analyses, but also efforts to bring an outbreak under control. Our findings give epidemiological support to recent molecular studies which suggest that fluoroquinolone use may increase the transmissibility of MRSA in hospitals.

Adult↗

Modulatory effect of endogenous and exogenous opioids on the excitatory reflex pathway of the rat ileum.

The ascending excitatory reflex is part of the peristaltic reflex, an important participant in intestinal propulsion. The aim of this study was to characterize the role of different opioid receptors in the ascending reflex through exogenous application of non-selective (Met-enkephalin) and selective opioid agonists (mu-PLO17, delta-DPDPE, kappa-U-50, 488) as well as selective opioid receptor antagonists (mu: CTOP-NH(2), delta: ICI-174,864, kappa: Nor-Binaltorphimine). Metenkephalin (IC(50): 0.06 microM) and morphine (IC(50): 1.8 microM) inhibited the ascending reflex response concentration-dependently. Both the mu-selective agonist PLO17 (IC(50): 0.83 microM, n =11) and the kappa-selective agonist U-50,488 (IC(50): 0.68 microM, n =8) concentration-dependently inhibited the magnitude of the ascending contractile reflex response, whereas the delta-agonist DPDPE (10(-10)-10(-6)M) had no significant effect. In contrast, the latency of the response (time interval between start of the stimulus and onset of the contraction) was significantly prolonged by PLO17 > morphine > Met-enkephalin > DPDPE, whereas U-50,488 showed no effect. When the effect of the receptor-specific antagonists was tested, only CTOP-NH(2)and Nor-BNI caused a significant increase of the contractile response, whereas ICI-174 864 was ineffective. On the other hand, CTOP-NH(2)> ICI-174 864 decreased the latency significantly but the kappa-receptor agonist Nor-BNI had no influence. Thus, mu- and kappa-receptors seem to be involved in regulating the contraction strength of the ascending reflex, whereas both mu- and delta-receptors seem to be involved in the timing of the reflex response.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Paraneoplastic cerebellar degeneration in pediatric Hodgkin disease.

Paraneoplastic cerebellar degeneration (PCD) is a rare neurological complication in adults with extracerebral neoplasms. It is characterized by a diffuse cerebellar dysfunction, usually leading to severe neurological sequelae. In childhood, this complication is extremely rare. We report on PCD as primary manifestation of Hodgkin disease (HD) in a thirteen-year old boy. On magnetic resonance imaging, irreversible atrophy of the cerebellum developed within three months. Antibodies against Purkinje cells were detectable at diagnosis and normalised after successful treatment of the lymphoma. Cerebellar symptoms, however, only partially resolved. The necessity of a search for a malignant tumour is emphasised in the presence of an otherwise unexplained, subacutely developing, diffuse cerebellar dysfunction.

Adolescent↗

Characterization of the endothelin receptor subtypes in human prostate.

Endothelin (ET) receptor subtypes in human prostate with benign prostatic hyperplasia were investigated by binding and functional studies. In the displacement experiment, LU224332 [endothelin-A/-B (ET(A)/ET(B)) nonselective antagonist] competed for [125I]ET-1 binding with a monophasic curve. On the other hand, LU135252 (ET(A)-selective antagonist) and sarafotoxin S6c (S6c, ET(B)-selective agonist) competed for [125I]ET-1 binding with shallow and biphasic curves. The analysis of the displacement curves for LU135252 and S6c showed that both ET(A) and ET(B) subtypes coexist but that ET(A) is the dominantly expressed receptor. In human prostate strips, 10 microM of both LU135252 and LU224332 strongly inhibited the contractile response to ET-1 with equal potency. However, 10 microM of BQ788 (ET(B)-selective antagonist) did not show a clear inhibition. S6c also produced a contractile response, which was potently inhibited by LU224332 or BQ788, and slightly suppressed by LU135252. These results suggest that in human prostate both ET(A) and ET(B) subtypes are functional receptors mediating contraction, but that ET-1-mediated contractions are predominantly mediated by activation of dominant receptor subtype, ET(A).

Aged↗

Atypical benign partial epilepsy/pseudo-Lennox syndrome.

The purpose of this report is to describe the full clinical and electroencephalograpic spectrum of atypical benign partial epilepsy (ABPE) or pseudo-Lennox syndrome (PLS). We retrospectively analyzed the clinical and EEG data of 43 children with ABPE/PLS seen in our department during the last 25 years. Criteria for diagnosis of ABPE/PLS were the occurrence of generalized minor seizures as previously described for ABPE/PLS and the detection of focal sharp waves indistinguishable from those of rolandic epilepsy (RE) with generalization during slow sleep. Mental development prior to onset of epilepsy was retarded in 26% of patients. In 74%, age at onset of seizures ranged from 2-5 years of age. Atonic-astatic seizures, atypical absences, and more rarely, myoclonic seizures were the predominating seizure types in 67% of patients. Status of minor seizures occurred in 40%. One or several episodes of partial and secondarily generalized seizures were observed. Rolandic seizures occurred in 28%. The EEG was characterized by a normal or slightly slowed background activity and predominantly multi-focal sharp waves (88%) which were activated to a bioelectrical status in 56% during sleep. No tonic seizures and no fast > 10 Hz spike discharges were observed in any of the 1.291 EEG of the patients. Despite an often temporarily therapy-resistant course which led to use of steroids in 51% of patients, seizures had ceased in 84% and epileptic discharges had disappeared in 72% of patients at last follow-up. All patients older than age 15 were seizure-free. However, the rate of mentally handicapped patients had more than doubled from 26 to 56%. EEG which could be performed in 41 out of 56 siblings demonstrated shw in 40% of siblings in whom EEG were done at the age of maximum penetrance of sharp waves (3-10 years). ABPE/PLS overlaps broadly with RE, but also with electrical status epilepticus during sleep and Landau-Kleffner syndrome. Therefore, ABPE/PLS can be ranked alongside RE and other idiopathic partial epilepsies. The high incidence of sharp waves in siblings suggests that ABPE/PLS and RE have a common underlying genetic etiology.

Adolescent↗

Ginkgo biloba: local experiences.

Ginkgo biloba (EGb 761) as a phytotherapeutic agent used in otoneurology, psychiatry, and ophthalmology. We studied the efficacy of therapy with EGb 761 in 72 patients (44 male and 28 female) with chronic cochleovestibular disorders. We used pure-tone audiology, measuring pure-tone average, speech reception threshold, and speech discrimination score. Then we used craniocorpography to measure lateral body sway and angular deviation. Finally, we used nystagmography (central nystagmic frequency). Also, we assessed subjectively the variation in patients' comfort. We concluded that EGb 761 has a very good effect on both postural and oculovestibular reflexes. Also, hearing was improved, and patients' comfort was considered to be heightened by the therapy.

Audiometry↗

Audiovestibular findings prior to and after acoustic neuroma surgery.

We performed a retrospective study of 131 patients who underwent microsurgical removal of statoacoustic neuroma at the University of Wuerzburg. Our goal was to evaluate objective audiovestibular findings prior to and after surgery. Our analysis focused on the evaluation of quantitative parameters in speech and pure-tone audiometry and on the reactivity of the vestibular system.

Adolescent↗

Independent regulation of cyclo-oxygenase 2 expression by p42/44 mitogen-activated protein kinases and Ca2+/calmodulin-dependent kinase.

5-Hydroxytryptamine (5-HT, 'serotonin') is a potent inducer of the early response gene cyclo-oxygenase 2 (Cox-2; prostaglandin G/H synthase) in mesangial cells. Protein kinase C (PKC), Ca2+-dependent enzymes and mitogen-activated protein kinase (p42/44 MAPK) have previously been shown to be essential modules of the signalling pathway leading from the pertussis-insensitive 5-HT2A receptor to the induction of Cox-2 mRNA expression. In the present study, PKC activation was linked to the 5-HT-mediated phosphorylation and thus the activation of p42/44 MAPK: the inhibition of PKC by the specific inhibitor GF109203x prevented p42/44 MAPK activation. Ca2+/calmodulin-dependent (CaM) kinase II delta2 was detected in mesangial cells by Western blot analysis. The inhibition of CaM kinase by the inhibitors KN62 or KN93 led to a partial inhibition of 5-HT-induced Cox-2 mRNA expression and decreased basal, but not PMA-mediated, Cox-2 expression. The 5-HT-mediated activation of MAPK was not decreased by KN62 or KN93, excluding CaM kinase as a signalling module upstream of p42/44 MAPK. Taken together, these results indicate a modulatory involvement of CaM kinase in the regulation of 5-HT-mediated Cox-2 mRNA expression in addition to the main pathway that consists of the activation of PKC and p42/44 MAPK.

Animals↗

Linkage analysis with adequate modeling of a parent-of-origin effect.

We present an extension to parametric linkage analysis that allows modeling diseases with a parent-of-origin effect (i.e., imprinting). Different penetrances are assumed for individuals being heterozygous at the disease locus, depending on their having inherited the disease allele from the father or mother. Motivated by the finding of a maternally expressed locus influencing alcohol consumption in mice (Alcp2), the analysis method has been included into the program GENEHUNTER for application to Problem 1, Collaborative Study on the Genetics of Alcoholism of Genetic Analysis Workshop 11. By this extension, a powerful tool is provided for adequately modeling an inherited disease in linkage analysis that supposedly has imprinting effects. The program has been used to analyze the data set on alcohol dependence in humans and can be applied to other genetically determined traits as well.

Alcoholism↗

Linkage analysis in alcohol dependence.

Alcohol dependence often is a familial disorder and has a genetic component. Research in causative factors of alcoholism is coordinated by a multi-center program, COGA [The Collaborative Study on the Genetics of Alcoholism, Begleiter et al., 1995]. We analyzed a subset of the COGA family sample, 84 pedigrees of Caucasian ancestry comprising 745 persons, 339 of whom are affected according to DSM-III-R and Feighner criteria. Using parametric and nonparametric methods, evidence for linkage was found on chromosome 1 (near markers D1S532, D1S1588, and D1S534), as well as on chromosome 15 (near marker D15S642). Other regions of the genome showed suggestive evidence for contributing loci. Related findings are discussed in recent publications investigating linkage in humans [Reich et al., 1998] and mice [Melo et al., 1996].

Alcoholism↗

Glycerol hyperhydration improves cycle time trial performance in hot humid conditions.

Eight competitive cyclists [mean peak oxygen consumption, (VO2(peak)) = 65 ml x min(-1) x kg(-1)] undertook two 60-min cycle ergometer time trials at 32 degrees C and 60% relative humidity. The time trials were split into two 30-min phases: a fixed-workload phase and a variable-workload phase. Each trial was preceded by ingestion of either a glycerol solution [1 g x kg(-1) body mass (BM) in a diluted carbohydrate (CHO)-electrolyte drink] or a placebo of equal volume (the diluted CHO-electrolyte drink). The total fluid intake in each trial was 22 ml x kg(-1) BM. A repeated-measures, double blind, cross over design with respect to glycerol was employed. Glycerol ingestion expanded body water by approximately 600 ml over the placebo treatment. Glycerol treatment significantly increased performance by 5% compared with the placebo group, as assessed by total work in the variable-workload phase (P < 0.04). There were no significant differences in rectal temperature, sweat rate or cardiac frequency between trials. Data indicate that the glycerol-induced performance increase did not result from plasma volume expansion and subsequently lower core temperature or lower cardiac frequencies at a given power output as previously proposed. However, during the glycerol trial, subjects maintained a higher power output without increased perception of effort or thermal strain.

Adult↗

Chromosome mechanics of fungi under spaceflight conditions--tetrad analysis of two-factor crosses between spore color mutants of Sordaria macrospora.

Spore color mutants of the fungus Sordaria macrospora Auersw. were crossed under spaceflight conditions on the space shuttle to MIR mission S/MM 05 (STS-81). The arrangement of spores of different colors in the asci allowed conclusions on the influence of spaceflight conditions on sexual recombination in fungi. Experiments on a 1-g centrifuge in space and in parallel on the ground were used for controls. The samples were analyzed microscopically on their return to earth. Each fruiting body was assessed separately. Statistical analysis of the data showed a significant increase in gene recombination frequencies caused by the heavy ion particle stream in space radiation. The lack of gravity did not influence crossing-over frequencies. Hyphae of the flown samples were assessed for DNA strand breaks. No increase in damage was found compared with the ground samples. It was shown that S. macrospora is able to repair radiation-induced DNA strand breaks within hours.

Ascomycota↗

Gustometry of diabetes mellitus patients and obese patients.

The sensation of adequate taste detection can be associated with satisfaction of food intake. The impairment of taste detection may be associated with the development of obesity. Taste detection is determined hereditarily, but it can be influenced also by the occurrence of neuropathy. To find an explanation for these phenomena, we investigated 73 patients with diabetes mellitus (DM) 2 (i.e., non-insulin-dependent DM); 11 patients with DM 1 (i.e., insulin-dependent DM); 12 obese patients (body-mass index >30) without DM; and 29 control patients. All subjects underwent electrogustometric examination with Hortmman's electrogustometer. During this examination, we obtained electrical thresholds of taste by stimulating appropriate parts of the tongue. We stimulated the apex, middle, and near tongue radix areas on both sides. The resulting value is the average on the left and right sides of the mentioned areas. We considered a value of less than 40 microA to be normal. Values in excess of 100 microA are considered as hypogeusia. Values between 40 and 100 microA are taken as borderline, and ageusia is in excess of 500 microA. According to these criteria, in the DM 2 group, we found 40% of patients with hypogeusia, whereas in the DM 1 group, we found 33% of patients; 25% of patients were in the obese group. Among normal subjects (people without obesity or DM), no hypogeusia was found. We found ageusia in 5% of patients with DM 2, in 3% of patients with DM 1, and in 14% of obese patients. Among normal subjects, we found no ageusia. These results support the hypothesis that diminished taste detection can evoke hyperphagia and later obesity.

Adolescent↗

Effect of interleukin-1beta on the ascending and descending reflex in rat small intestine.

Acute inflammation of the intestine is associated with motility changes. We investigated the acute effect of inflammatory mediators such as interleukin-1beta, interleukin-2 and tumor necrosis factor-alpha (TNF-alpha) on electrically stimulated ascending and descending reflex responses of the rat small intestine. Exogenous application of interleukin-1beta caused a concentration-dependent inhibition of the oral contraction (0.1 ng/ml: -22.9+/-3.8%, 10 ng/ml: -57.0+/-7.4%, P < 0.05, n=10) but had no effect on anal relaxation. The interleukin-1 receptor antagonist alone had no significant effect on the reflex response, but prevented the inhibitory effect of interleukin-1beta (10 ng/ml: -3.9+/-11.4%, n=8). Interleukin-2 and TNF-alpha had no significant effect on the oral contractile and the anal inhibitory response (n.s., n=10). Using reverse transcriptase polymerase chain reaction (RT-PCR) the presence of mRNA of the interleukin-1 receptor was demonstrated in the rat small intestine. Preincubation of the preparation with indomethacin (10(-6) M), the histamine H1 receptor antagonist, pyrilamine (10(-8) M), and the histamine H3 receptor antagonist, clobenpropit (10(-8) M), decreased the oral contraction by 60.1+/-7.7%, 42.8+/-6.9% and 44.4+/-14.2% as well as the anal relaxation. These data suggest that acute administration of interleukin-1beta inhibits the ascending and descending contractile reflex pathway and this effect seems not to be mediated by prostaglandins or histamine receptors.

Animals↗

Elite endurance athletes and the ACE I allele--the role of genes in athletic performance.

Genetic markers that might contribute to the making of an elite athlete have not been identified. Potential candidate genes might be found in the renin-angiotensin pathway, which plays a key role in the regulation of both cardiac and vascular physiology. In this study, DNA polymorphisms derived from the angiotensin converting enzyme (ACE), the angiotensin type 1 receptor (AT1) and the angiotensin type 2 receptor (AT2) were studied in 64 Australian national rowers. Compared with a normal population, the rowers had an excess of the ACE I allele (P<0.02) and the ACE II genotype (P=0.03). The ACE I allele is a genetic marker that might be associated with athletic excellence. It is proposed that the underlying mechanism relates to a healthier cardiovascular system.

Adult↗