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Biomedical subjects

A Diehl

Publications and source records attributed to A Diehl.

At least 19 recordsLinked to original sources
PubMed2007

[Pharmacological relapse prevention in alcohol and tobacco dependence].

A better understanding of the neurobiological substrates of alcohol and tobacco dependence has been accompanied by the increasing role of pharmacological relapse prevention. In alcohol dependence, substances which are able to block or ameliorate alcohol craving improve the maintenance of abstinence in combination with psychosocial treatment. In particular, the N-methyl-D-aspartate receptor antagonist acamprosate and the opiate receptor antagonist naltrexone have been shown to be effective in numerous trials. Administration starts immediately after detoxification and should last for 12 months. This treatment, however, is not a replacement for the psychosocial treatment of the alcohol dependence. Compared with placebo treatment, approximately twice as many patients remain abstinent under acamprosate 1 year after the end of treatment. The most widely studied and used pharmacotherapy for the treatment of tobacco dependence is nicotine containing medications. Nicotine replacement therapies (patch, gum, tablet, inhaler) have been shown to reduce tobacco craving and enhance abstinence. The only non-nicotine medication that has been approved in Germany is the antidepressant bupropion. Current studies identify particularly suitable subgroups of patients responding to more individualized pharmacological relapse prevention. A specific application of these substances will optimise the outcome for alcohol and tobacco dependent patients.

Acamprosate↗
PubMed2007

[Carbamazepine intoxication. Complication of alcohol detoxification with combined carbamazepine and tiapride].

The advantages of alcohol detoxification treatment with combined carbamazepine and tiapride compared to benzodiazepines or clomethiazole is a lower level of sedation and lack of addictive potential. We report a case of carbamazepine intoxication with serum levels up to 19 mg/l in an otherwise healthy 45-year-old alcohol-dependent male after treatment with 600 mg carbamazepine and 600 mg tiapride per day. Medication was discontinued immediately and a purgative was administered. We were able to combat the intoxication but the assumed good tolerance of the combined treatment with carbamazepine and tiapride for alcohol detoxification still has to be proven.

Alcoholism↗
PubMed2006

Quetiapine in relapse prevention in alcoholics suffering from craving and affective symptoms: a case series.

PURPOSE: Quetiapine is a novel antipsychotic, which is efficacious in the treatment of positive and negative symptoms in schizophrenia. Research has shown that atypical antipsychotic also reduce the craving and consumption for stimulants and alcohol. Due to Quetiapine's particulars and the promising receptor profile concerning addiction medicine, we set out to examine the tolerability and efficacy concerning relapse prevention of withdrawn alcoholics suffering from craving and affective symptoms. SUBJECTS AND METHODS: Our case observations attempted to evaluate nine alcoholics after withdrawal suffering from persisting craving, sleep disorder, excitement, depressive symptoms or anxiety symptoms. The patients were treated with quetiapine as relapse prevention and we followed them up in our outpatient clinic. RESULTS: Eight out of nine patients were abstinent under quetiapine over a period of 2-7 months. One of these patients relapsed after he stopped taking the preparation at his own initiative after 10 weeks. The ninth patient stopped taking the preparation immediately because of swollen nasal mucosae. All target symptoms disappeared in the patients after an average of (mean+/-S.D.) 24.5+/-18.1 days. The overall tolerability was considered to be very good; however, initial sleepiness appeared in four patients. CONCLUSION: Although uncontrolled case observations can only be interpreted with caution quetiapine seems to deserve further investigation and may hold the potential for preventing alcohol relapse in alcoholics suffering from additional above-mentioned symptoms.

Adult↗
PubMed2006

Galantamine reduces smoking in alcohol-dependent patients: a randomized, placebo-controlled trial.

INTRODUCTION: The high morbidity and mortality caused by smoking highlights the importance of investigating new strategies for smoking cessation or reduction. Galantamine is an acetylcholinesterase inhibitor that increases the effect of acetylcholine (ACh). The nicotinic ACh receptor is activated via positive allosteric modulation (APL). METHODS: We investigated whether galantamine reduces smoking by performing a 24-week randomized, placebo-controlled, multicentric clinical trial in recently detoxified alcohol-dependent patients. We included all study subjects irrespective of an intention or motivation to abstain from nicotine. Specific treatment for cessation or reduction of smoking was not provided. Smoking behavior was assessed by means of patients' diaries. The nicotine metabolite cotinine was measured to verify the number of smoked cigarettes as documented in the patient's diary. RESULTS: 114 randomized smokers received galantamine (n = 56) or placebo (n = 58) for 12 weeks. Follow-up examinations were terminated after an additional 12 weeks without treatment. Smoking behavior did not differ between both groups at baseline. After treatment, the intention-to-treat analysis revealed significant differences with a 20% lower cumulative number of smoked cigarettes and a 15% lower number of smoking days in the galantamine group compared to placebo. The average number of smoked cigarettes per smoking day as well as the cotinine values decreased about 10%. Cotinine values showed a positive correlation with the number of documented cigarettes, validating the patients' diaries. CONCLUSION: Our tentative data indicate that galantamine reduces smoking behavior even without any additional specific intervention. We suggest introducing the term "substitution therapy" into the treatment of smoking. This result could open up a new treatment approach for groups of patients which usually have a low motivation for change.

Administration, Cutaneous↗
PubMed2005

Galantamine: a cholinergic patch in the treatment of alcoholism: a randomized, placebo-controlled trial.

OBJECTIVES: The involvement of the central cholinergic system in alcohol abuse behavior is well known. It is possible that the reinforcing effects of ethanol are partially mediated by nicotinic receptors, which modulate neurotransmitter release. It was demonstrated that the application of a cholinesterase inhibitor reduces alcohol consumption in alcohol-preferring rats. This suggests that galantamine (GAL), a cholinesterase inhibitor, could be effective when seeking to prolong abstinence in recently detoxified alcoholics. This study represents the first reported clinical trial of a cholinergic drug in alcohol-relapse prevention. PATIENTS AND METHODS: We investigated the efficacy and safety of GAL by conducting a 24-week randomized, placebo-controlled, multicentric clinical trial on 149 recently detoxified alcoholics. Survival analyses (Kaplan-Meier) were performed to reveal evidence of prolonged abstinence periods in patients who received GAL. RESULTS: Our findings did not support our hypothesis. GAL did not extend the time to first severe relapse. However, additional post hoc analyses suggest that relapsed patients treated with GAL consume less ethanol per drinking day than patients treated with placebo. CONCLUSIONS: GAL seems to be ineffective when used in relapse prevention of detoxified alcoholics. It is possible that alcohol needs to be "on board" for GAL to be beneficial. This could explain why our post hoc analysis showed that GAL possibly reduces the alcohol consumption of relapsers. If confirmed, GAL could play a role in the reduction of harmful alcohol use and at-risk consumption.

Administration, Cutaneous↗
PubMed2005

Scheme-based benzodiazepine detoxification with oxcarbazepine -- a case report.

We attempted to evaluate the tolerability and efficacy of the antiepileptic drug oxcarbazepine in benzodiazepine detoxification, by observing several cases. Detoxification followed a predefined dosage scheme. All patients detoxified with oxcarbazepine completed the withdrawal successfully, without withdrawal symptoms. The administration of oxcarbazepine according to the scheme proved to be tolerable. The dosage was sufficient. Though uncontrolled case observations must be interpreted with caution, oxcarbazepine appears to be a promising drug in inpatient benzodiazepine withdrawal. It should be examined in further randomized placebo-controlled studies including long-term follow-ups.

Anticonvulsants↗
PubMed2005

Neuroimaging of gender differences in alcohol dependence: are women more vulnerable?

BACKGROUND: Alcoholic brain damage has been demonstrated in numerous studies using neuropathology and brain imaging techniques. However, gender differences were addressed only in a few studies. Recent research has shown that development, course, and consequences of alcohol dependence may differ between female and male patients. Our investigation was built upon earlier research where we hypothesized that women develop alcoholic brain damage more readily than men do. To further compare the impact of alcohol dependence between men and women, we examined brain atrophy in female and male alcoholics by means of computed tomography (CT). METHODS: The study group consisted of a total of 158 subjects (76 women: 42 patients, 34 healthy controls; 82 age-matched men: 34 patients, 48 healthy controls). All patients had a DSM-IV and ICD-10 diagnosis of alcohol dependence. CT with digital volumetry was performed twice in patients (at the beginning and end of the 6-week inpatient treatment program) and once in controls. RESULTS: Patients of both genders had consumed alcohol very heavily. Although the average alcohol consumption in the year before the study was significantly lower in female alcoholics, this gender difference disappeared when controlled for weight. However, women had a significantly shorter duration of alcohol dependence. Despite this fact, both genders developed brain atrophy to a comparable extent. Brain atrophy was reversible in part after 6 weeks of treatment; it did not reach the level in the control groups. CONCLUSIONS: Gender-specific differences in the onset of alcohol dependence were confirmed. This is in line with the telescoping effect, where a later onset and a more rapid development of dependence in women were described. Under the assumption of a gradual development of consequential organ damage, brain atrophy seems to develop faster in women. As shown in other organs (i.e., heart, muscle, liver), this may confirm a higher vulnerability to alcohol among women.

Adult↗
PubMed2004

Olanzapine versus flupenthixol in the treatment of inpatients with schizophrenia: a randomized double-blind trial.

OBJECTIVE: The atypical antipsychotic olanzapine has extensively been compared with haloperidol, whereas studies vs. other (conventional) neuroleptics are scarce. This exploratory double-blind 4-week study was designed to compare the efficacy and the safety of olanzapine (OLA) and flupenthixol (FLU) which have recently been considered as a "partially atypical" antipsychotics. METHODS: Twenty-eight inpatients with schizophrenia (DSM-IV) were randomly assigned for treatment with OLA (N = 15, 5-20 mg/d) or FLU (N = 13, 5-20 mg/d). The Brief Psychiatric Rating Scale (BPRS) and the Negative Symptoms Rating Scale (NSRS), plus the Patient Global Impression (PGI) and Clinical Global Impression (CGI) scales, were used to assess the efficacy of both compounds; safety was determined by using the Simpson Angus Scale (SAS) and the Abnormal Involuntary Movement Scale (AIMS) and by assessing treatment-emergent adverse events. Non-parametric statistics were applied. RESULTS: BPRS and NSRS scores improved in both groups (exploratory tests; all p < or = 0.02). Similar results were observed for CGI-Severity, CGI- and PGI-Improvement. There were no significant group differences. Responder rates (at least 40 % decrease in BPRS total) were 9/13 OLA patients (69 %) and 9/12 FLU patients (75 %). EPS events were reported only in the FLU group (p < 0.01); FLU patients needed significantly more anticholinergic medication. Weight gain was higher in OLA patients (p < 0.01). Overall, fewer patients with adverse events were observed in the OLA group (p = 0.04). No significant changes were noted on SAS and AIMS scores. CONCLUSION: Findings from this study suggest that overall and negative symptomatology improved in both treatment groups, while the safety and tolerability profiles differed for both substances.

Adult↗
PubMed2003

Resonant Electron Transfer in Collisions between Two Fullerene Ions.

Fullerenes are a direct link between atoms with discrete electronic energy levels and solids with a band structure and a well-defined surface. In this Letter, we report on the first ever experiment on resonant electron transfer in collisions between two fullerene ions. Total cross sections have been measured for the reaction C+60+C2+60-->C2+60+C+60 at center-of-mass energies ranging from 27 to 69 keV. Surprisingly, within the error bars, these cross sections are identical to the respective cross sections for C+60+C60 measured by Rohmund and Campbell [J. Phys. B 30, 5293 (1997)]]. We show that the experimental data for both collision systems are very well reproduced by a quantum mechanical treatment of the reaction based on the concept of hole particles and the polarizability of the fullerene molecule.

Journal Article↗
PubMed2002

Dynamics and embolic activity of symptomatic intra-cranial cerebral artery stenoses.

OBJECTIVE: To investigate the occurrence of microembolic signals (MES) and hemodynamic features in patients with acute symptomatic intracranial cerebral artery stenoses by transcranial Doppler (TCD). MATERIAL AND METHODS: Twelve patients with acute hemispheric ischemic events and corresponding intracranial cerebral artery stenoses as identified by TCD, and exclusion of extracranial or cardiac emboli sources were repeatedly studied by TCD monitoring of the affected and the contralateral vessel. The occurrence of MES and MES clusters (> or =3 MES per second) and of flow velocity changes was examined. RESULTS: Nine patients presented with MES in the affected artery during the first measurement. In seven patients sudden flow velocity changes could be detected in the affected vessel. In five patients these changes were accompanied by MES clusters. MES and velocity changes disappeared in all patients during follow-up, and the degree of stenosis decreased in nine patients. CONCLUSIONS: The high prevalence of MES and sudden velocity changes in acute intracranial cerebral artery stenoses indicates that acute intracranial stenoses may be formed at least in part by mobile thrombotic material.

Adult↗
PubMed2001

Counterion correlations and attraction between like-charged macromolecules.

A simple model is presented for the appearance of attraction between two like-charged polyions inside a polyelectrolyte solution. The polyions are modeled as rigid cylinders in a continuum dielectric solvent. The strong electrostatic interaction between the polyions and the counterions results in counterion condensation. If the two polyions are sufficiently close to each other their layers of condensed counterions can become correlated resulting in attraction between the macromolecules. To explore the counterion induced attraction we calculate the correlation functions for the condensed counterions. It is found that the correlations are of very short range. For the parameters specific to the double stranded DNA, the correlations and the attraction appear only when the surface-to-surface separation is less than 7 A.

Biophysics↗
PubMed2000

The fib locus in Streptococcus pneumoniae is required for peptidoglycan crosslinking and PBP-mediated beta-lactam resistance.

Penicillin resistance in pneumococci is mediated by modified penicillin-binding proteins (PBPs) that have decreased affinity to beta-lactams. In high-level penicillin-resistant transformants of the laboratory strain Streptococcus pneumoniae R6 containing various combinations of low-affinity PBPs, disruption of the fib locus results in a collapse of PBP-mediated resistance. In addition, crosslinked muropeptides are highly reduced. The fib operon consists of two genes, fibA and fibB, homologous to Staphylococcus aureus femA/B which are also required for expression of methicillin resistance in this organism. FibA and FibB belong to a family of proteins of Gram-positive bacteria involved in the formation of interpeptide bridges, thus representing interesting new targets for antimicrobial compounds for this group of pathogens.

Amino Acid Sequence↗
PubMed2000

Interaction of fMet-tRNA(fMet) with the C-terminal domain of translational initiation factor IF2 from Bacillus stearothermophilus.

Analytical ultracentrifugation studies indicated that the C-terminal domains of IF2 comprising amino acid residues 520-741 (IF2 C) and 632-741 (IF2 C-2) bind fMet-tRNA with similar affinities (K(d) at 25 degrees C equal to 0.27 and 0.23 microM, respectively). Complex formation between fMet-tRNA(fMet) and IF2 C or IF2 C-2 is accompanied by barely detectable spectral changes as demonstrated by a comparison of the Raman spectra of the complexes with the calculated sum of the spectra of the individual components. These results and the temperature dependence of the K(d) of the protein-RNA complexes indicate that complex formation is not accompanied by obvious conformational changes of the components, and possibly depends on a rather small binding site comprising only a few interacting residues of both components.

Bacterial Proteins↗
PubMed2000

X-ray structure of the quinoprotein ethanol dehydrogenase from Pseudomonas aeruginosa: basis of substrate specificity.

The homodimeric enzyme form of quinoprotein ethanol dehydrogenase from Pseudomonas aeruginosa ATCC 17933 crystallizes readily with the space group R3. The X-ray structure was solved at 2.6 A resolution by molecular replacement. Aside from differences in some loops, the folding of the enzyme is very similar to the large subunit of the quinoprotein methanol dehydrogenases from Methylobacterium extorquens or Methylophilus W3A1. Eight W-shaped beta-sheet motifs are arranged circularly in a propeller-like fashion forming a disk-shaped superbarrel. No electron density for a small subunit like that in methanol dehydrogenase could be found. The prosthetic group is located in the centre of the superbarrel and is coordinated to a calcium ion. Most amino acid residues found in close contact with the prosthetic group pyrroloquinoline quinone and the Ca(2+) are conserved between the quinoprotein ethanol dehydrogenase structure and that of the methanol dehydrogenases. The main differences in the active-site region are a bulky tryptophan residue in the active-site cavity of methanol dehydrogenase, which is replaced by a phenylalanine and a leucine side-chain in the ethanol dehydrogenase structure and a leucine residue right above the pyrrolquinoline quinone group in methanol dehydrogenase which is replaced by a tryptophan side-chain. Both amino acid exchanges appear to have an important influence, causing different substrate specificities of these otherwise very similar enzymes. In addition to the Ca(2+) in the active-site cavity found also in methanol dehydrogenase, ethanol dehydrogenase contains a second Ca(2+)-binding site at the N terminus, which contributes to the stability of the native enzyme.

Alcohol Oxidoreductases↗
PubMed2000

Scaling behavior in explosive fragmentation

We investigate the explosive fragmentation process in two dimensions using molecular-dynamics simulations. We show that the mass distribution of fragments follows a power law, with a scaling exponent that is strongly dependent on the macroscopic characteristics of the system prior to the explosion process. In particular, for thermalized initial configurations at low temperatures, we observe that the exponent is close to -1. We suggest that this result can be interpreted in terms of a multiplicative fracture process.

Journal Article↗
PubMed2000

Histoplasmosis of the thyroid.

Fungal infection of the thyroid is rare. Most reported cases have involved Aspergillus, Coccidioides, and Candida species in the setting of disseminated disease. Infection of the thyroid with Histoplasma capsulatum is rarely reported as part of disseminated disease, even in geographic areas where histoplasmosis is endemic. We report a 52-year-old woman with a previous Hashimoto's disease and non-Hodgkin's lymphoma in which a diffuse enlarged thyroid gland with a large nodule was the only apparent locus of histoplasmosis. Fine-needle aspiration of the thyroid was an important diagnostic tool in establishing the diagnosis of histoplasmosis of the thyroid. The patient was initially treated with itraconazole (400 mg/day) for the fungal infection and six cycles of chemotherapy for the lymphoma. At a 6-month follow-up examination, the patient was doing well on suppressive therapy of itraconazole (200 mg/day), with no symptoms and with regression of the thyroid nodule and cervical adenopathy.

Antifungal Agents↗