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Biomedical subjects

S Evers

Publications and source records attributed to S Evers.

At least 73 records · Page 4Linked to original sources
PubMed2001

[Pain therapy in HIV-associated polyneuropathy].

Only some patients with HIV-infection receive an adequate pain therapy. In later stages of HIV-infection up to 50% 6 of patients perform extraordinary doctor visits because of pain. Principally primary and secondary neuromanifestations of HIV-infection have to be differentiated. Rare forms of HIV-associated polyneuropathies represent mononeuropathy or mononeuritis multiple acute and chronic inflammatory demyelinating polyneuropathy and polyneuropathy caused by opportunistic infections. HIV-associated distal-symmetric polyneuropathy represents the most common form during HIV-infection with a prevalence up to 50%. Typical clinical symptoms and signs are pain, hyp- and dysaesthesia, diminuted deep tendon reflexes, motor deficits and autonomic disturbances. Always neurological examination and neurophysiologic investigation on the sural and peronaeal nerve are necessary for monitoring progression of polyneuropathy and as basics before starting antiretroviral therapy with neurotoxic substances. According to momentary opinion, HIV-associated distal-symmetric polyneuropathy represents no indication for antiretroviral therapy. Symptomatic therapy includes antiepileptic medication as gabapentine, antidepressive drugs as amitiptyline and additionally retarded opiates. Depressive disorders ma y accentuate pain problems a n d need psychotherapeutic and thymoleptic therapy. Special problems occur when neurotoxic substances evoke or deteriorate polyneuropathy. In these cases an individual therapeutic proceeding about continuation or discontinuation of neurotoxic medication is necessary. Symptoms of myopathy during HIV-infection are muscle pain, elevation of CK and typical changes of motor units detected by electromyography. In most cases biopsy is necessary for diagnosis of specific forms of HN-associated myopathy. HIV-associated polymyositis is treated by non-steroid analgetics, corticoids, immunoglobulines and plasmapheresis, myopathy induced by neurotoxic medication analogous to polyneuropathy.

Acute Disease↗
PubMed2001

Stroke and mental health care: a record linkage study.

BACKGROUND: Stroke is associated with psychiatric morbidity but little is known about mental health care use in stroke patients. METHOD: A probability record linkage study was conducted linking stroke cases admitted to a teaching hospital serving a catchment area between 1987 and 1995 with records from a psychiatric case register covering the same area. RESULTS: Stroke patients had a more than twofold increased risk of contact with mental health care than individuals in the general population (yearly prevalences of respectively 88 and 39 per 1000; risk ratio 2.24; 95 % CI 2.04-2.45). One-third of all stroke admissions had had mental health care before and more than half had had mental health care after the stroke. In the year of admission for stroke, the probability of receiving mental health care was highest, while in the more remote years the risk was lower. CONCLUSION: Stroke is associated with an increased probability of contact with mental health services. The pattern of mental health care of a stroke patient is different from that of other mental health patients: more episodic and concentrated around the time of admission for stroke.

Adult↗
PubMed2001

The impact of repetitive transcranial magnetic stimulation on pituitary hormone levels and cortisol in healthy subjects.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is a new therapeutic tool in the treatment of affective disorders but only few studies on its safety exist. We aimed to determine the impact of rTMS on (neuro)endocrinological serum levels by a placebo-controlled cross-over study. METHODS: 23 healthy subjects were stimulated by rTMS in a typical paradigm used in the treatment of depression (coil placed over left dorsolateral prefrontal cortex, 10 and 20 Hz stimulation). Placebo, infrathreshold, and suprathreshold stimulation were applied in random order. The serum levels of cortisol, prolactin, FSH, and TSH were measured before and after stimulation. RESULTS: After infrathreshold stimulation, cortisol and TSH serum levels decreased mildly but significantly. All other stimulations had no significant impact on hormone levels. In female, but not in male, subjects placebo stimulation yielded a significant increase of prolactin. CONCLUSIONS: rTMS as applied for the treatment of depression leads to only very mild and safe changes of hormones. These changes, in particular the decrease of cortisol levels, might explain in part the efficacy of rTMS.

Adult↗
PubMed2001

A comparative study of oral acetylsalicyclic acid and metoprolol for the prophylactic treatment of migraine. A randomized, controlled, double-blind, parallel group phase III study.

This study was a multinational, multicentre, double-blind, active controlled phase III trial designed to investigate efficacy and safety of 300 mg acetylsalicyclic acid (ASA) (n = 135) vs. 200 mg metoprolol (n = 135) in the prophylaxis of migraine. In total 270 (51 male and 219 female) patients, aged 18-65 years, suffering between two and six migraine attacks per month were recruited. The main objective was to show equivalence with respect to efficacy, defined as a 50% reduction in the rate of migraine attacks. A run-in phase was carried out with placebo for 4 weeks, followed by a 16-week drug phase. In both treatment groups the median frequency of migraine attacks improved during the study period, from three to two in the ASA group and from three to one in the metoprolol group; 45.2% of all metoprolol patients were responders compared with 29.6% with ASA. Medication-related adverse events were less frequent in the ASA group (37) than in the metoprolol group (73). The findings from this trial show that metoprolol is superior to ASA for migraine prophylaxis but has more side-effects. Acetylsalicylic acid is better tolerated than metoprolol. Using a strict responder criterion ASA showed a responder rate comparable with the placebo rate in the literature.

Adolescent↗
PubMed2001

Gene expression changes triggered by exposure of Haemophilus influenzae to novobiocin or ciprofloxacin: combined transcription and translation analysis.

The responses of Haemophilus influenzae to DNA gyrase inhibitors were analyzed at the transcriptional and the translational level. High-density microarrays based on the genomic sequence were used to monitor the expression levels of >80% of the genes in this bacterium. In parallel the proteins were analyzed by two-dimensional electrophoresis. DNA gyrase inhibitors of two different functional classes were used. Novobiocin, as a representative of one class, inhibits the ATPase activity of the enzyme, thereby indirectly changing the degree of DNA supercoiling. Ciprofloxacin, a representative of the second class, obstructs supercoiling by inhibiting the DNA cleavage-resealing reaction. Our results clearly show that different responses can be observed. Treatment with the ATPase inhibitor Novobiocin changed the expression rates of many genes, reflecting the fact that the initiation of transcription for many genes is sensitive to DNA supercoiling. Ciprofloxacin mainly stimulated the expression of DNA repair systems as a response to the DNA damage caused by the stable ternary complexes. In addition, changed expression levels were also observed for some genes coding for proteins either annotated as "unknown function" or "hypothetical" or for proteins not directly involved in DNA topology or repair.

Bacterial Proteins↗
PubMed2001

Peptide deformylase as an antibacterial drug target: assays for detection of its inhibition in Escherichia coli cell homogenates and intact cells.

An assay was developed to determine the activity of peptide deformylase (PDF) inhibitors under conditions as close as possible to the physiological situation. The assay principle is the detection of N-terminal [35S]methionine labeling of a protein that contains no internal methionine. If PDF is active, the deformylation of the methionine renders the peptide a substrate for methionine aminopeptidase, resulting in the removal of the N-terminal methionine label. In the presence of a PDF inhibitor, the deformylation is blocked so that the N-formylated peptide is not processed and the label is detected. Using this assay, it is possible to determine the PDF activity under near-physiological conditions in a cell-free transcription-translation system as well as in intact bacterial cells.

Amidohydrolases↗
PubMed2001

Peptide deformylase as an antibacterial drug target: target validation and resistance development.

New inhibitors of peptide deformylase (PDF) which are very potent against the isolated enzyme and show a certain degree of antibacterial activity have recently been synthesized by our group. Several lines of experimental evidence indicate that these inhibitors indeed interfere with the target enzyme in the bacterial cell. (i) The inhibition of Escherichia coli growth could be counteracted by overexpression of PDF from different organisms, including E. coli, Streptococcus pneumoniae, and Haemophilus influenzae. Conversely, reduced expression of PDF in S. pneumoniae resulted in an increased susceptibility to the inhibitors. (ii) Proteome analysis on two-dimensional gels revealed a shift for many proteins towards lower pI in the presence of PDF inhibitors, as would be expected if the proteins still carry their N-formyl-Met terminus. (iii) PDF inhibitors show no antimicrobial activity against E. coli under conditions that make growth independent of formylation and deformylation. The antibacterial activity in E. coli was characterized as bacteriostatic. Furthermore, the development of resistance in E. coli was observed to occur with high frequency (10(-7)). Resistant mutants show a reduced growth rate, and DNA sequence analysis revealed mutations in their formyl transferase gene. Taking all these aspects into account, we conclude that PDF may not be an optimal target for broad-spectrum antibacterial agents.

Amidohydrolases↗
PubMed2001

Integrated care across borders: possibilities and complexities.

The main purpose of this practice paper is to describe and analyse the possibilities and complexities of integrated health care across borders. First, we portray an ideal scenario for this type of care with a case of patients suffering from rheumatoid arthritis and living in the Dutch-Belgian frontier area. It shows how cross border care enhances continuity of care/tailor-made care and the other way around. Secondly, based on different literature sources, we describe actual regulations on health care across borders. We show that these regulations can be a major hindrance to integrated care. This raises questions on the scope and content of policies directed at both cross border and integrated care.

Journal Article↗
PubMed2001

Benefits and barriers associated with participation in food programs in three low-income Ontario communities.

Our objective was to identify the benefits and barriers associated with participation in food programs. We did a content analysis of focus groups with parents (n=21), teachers (n=10), project staff (n=21), and children (n=17) in three low-income Ontario communities. The key benefits identified by the three adult groups were hunger alleviation and social contact opportunities for both parents and children. Parents also benefited from volunteering with and/or participating in food programs because neighbourhood support networks developed. Teachers reported that children who attended breakfast programs became more attentive in school. The food programs also provided an opportunity for nutrition education. Offering food as part of all community programs (not just those designed to increase food availability) encouraged participation and increased attendance. Children thought that attending food programs kept them healthy, and helped them work harder in school. Parents' pride was the main barrier to participation in programs; however, parents who were actively involved in program delivery did not feel stigmatized accepting food. To encourage participation, nutrition professionals should collaborate with local residents to develop and implement community-based food programs.

Adolescent↗
PubMed2000

Piracetam versus acetylsalicylic acid in secondary stroke prophylaxis. A double-blind, randomized, parallel group, 2 year follow-up study.

Piracetam has been shown to inhibit platelet aggregation. Therefore, we performed a double-blind, randomized, parallel group study to compare the efficacy of daily 1600 mg piracetam t.i.d. vs. 200 mg acetylsalicylic acid (ASA) t.i.d. in secondary stroke prophylaxis. 563 patients after stroke as confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) were enrolled and received either piracetam or ASA during a 2 year follow-up period. The primary endpoint was the rate of stroke, transient ischaemic attack (TIA), or death from vascular cause. The secondary endpoint was the rate of adverse events leading to a premature discontinuation of the study medication. Patients were visited at home every 3 months and were examined in hospital after 1 and 2 years. At every visit, the platelet function was evaluated. No significant difference and no significant equivalence could be shown for the primary endpoint between the piracetam and the ASA group both in the intention-to-treat and in the per-protocol analysis. However, there was a not significant trend in favor of ASA (11.7 vs. 15.2%). After excluding those patients who did not respond to antiplatelet medication in vitro, however, piracetam and ASA were equivalent in secondary stroke prophylaxis (stroke, TIA, or vascular death 10.1% in the piracetam group vs. 9.7% in the ASA group). Piracetam was significantly superior to ASA in the secondary endpoint (P=0.0039). The data suggest that the overall efficacy of piracetam in secondary stroke prophylaxis is not as good as that of ASA but that piracetam is better tolerated. However, our data furthermore show that nonresponders to pharmacological inhibition of platelet function are more frequent under piracetam therapy and that they may influence the results of large studies on secondary prophylaxis in vascular diseases.

Aspirin↗
PubMed2000

Cerebrovascular ischemic events in wind instrument players.

Two cases of ischemic stroke due to carotid artery dissection occurring during wind instrument playing, probably caused by increased intrathoracic and subsequent intrapharyngeal pressure, are presented. A review of the literature revealed three similar patients with other types of cerebrovascular events, such as paradoxical cerebral embolism due to a patent foramen ovale and spinal epidural hematoma during trumpet playing.

Adult↗
PubMed2000

A combination of anti-CD3 and anti-CD7 ricin A-immunotoxins for the in vivo treatment of acute graft versus host disease.

This study evaluated the anti-graft versus host disease (GVHD) potential of a combination of immunotoxins (IT), consisting of a murine CD3 (SPV-T3a) and CD7 (WT1) monoclonal antibody both conjugated to deglycosylated ricin A. In vitro efficacy data demonstrated that these IT act synergistically, resulting in an approximately 99% elimination of activated T cells at 10(-8 )mol/L (about 1.8 microg/mL). Because most natural killer (NK) cells are CD7(+), NK activity was inhibited as well. Apart from the killing mediated by ricin A, binding of SPV-T3a by itself impaired in vitro cytotoxic T-cell cytotoxicity. Flow cytometric analysis revealed that this was due to both modulation of the CD3/T-cell receptor complex and activation-induced cell death. These results warranted evaluation of the IT combination in patients with refractory acute GVHD in an ongoing pilot study. So far, 4 patients have been treated with 3 to 4 infusions of 2 or 4 mg/m(2) IT combination, administered intravenously at 48-hour intervals. The T(1/2) was 6.7 hours, and peak serum levels ranged from 258 to 3210 ng/mL. Drug-associated side effects were restricted to limited edema, fever, and a modest rise of creatine kinase levels. One patient developed low-titer antibodies against ricin A. Infusions were associated with an immediate drop of circulating T cells, followed by a more gradual but continuing elimination of T/NK cells. One patient mounted an extensive CD8 T-cell response directly after treatment, not accompanied with aggravating GVHD. Two patients showed nearly complete remission of GVHD, despite unresponsiveness to the extensive pretreatment. These findings justify further investigation of the IT combination for treatment of diseases mediated by T cells. (Blood. 2000;95:3693-3701)

Acute Disease↗
PubMed2000

Two-dimensional map of the proteome of Haemophilus influenzae.

We have constructed a two-dimensional database of the proteome of Haemophilus influenzae, a bacterium of medical interest of which the complete genome, comprising about 1742 open reading frames, has been sequenced. The soluble protein fraction of the microorganism was analyzed by two-dimensional electrophoresis, using immobilized pH gradient strips of various pH regions, gels with different acrylamide concentrations and buffers with different trailing ions. In order to visualize low-copy-number gene products, we employed a series of protein extraction and sample application approaches and several chromatographic steps, including heparin chromatography, chromatofocusing and hydrophobic interaction chromatography. We have also analyzed the cell envelope-bound protein fraction using either immobilized pH gradient strips or a two-detergent system with a cationic detergent in the first and an anionic detergent in the second-dimensional separation. Different proteins (502) were identified by matrix-assisted laser desorption/ionization mass spectrometry and amino acid composition analysis. This is at present one of the largest two-dimensional proteome databases.

Databases, Factual↗
PubMed2000

[Acute psychiatric symptoms as the initial manifestation of HIV-infection: differential diagnosis, therapy and medico-legal issues].

The prevalence of psychiatric symptoms and disorders in HIV-infected patients is high. The differential diagnosis includes psychoreactive disorders, acute psychiatric symptoms of an HIV-associated encephalopathy, and symptomatic psychotic illnesses due to secondary neurologic manifestations such as opportunistic central nervous infections and intracerebral lymphoma. Clinical aspects and psychopathological findings are not sufficient for differential diagnosis and identification of primarily psychiatric disorders. Secondary neurologic manifestations causing a symptomatic psychosis must be excluded as soon as possible by brain imaging (CT, MRI) and analysis of the cerebrospinal fluid. In emergency situations, however, German law imposes strict regulations, especially in the case of sectioned patients. These medical and medicolegal questions are illustrated by case reports and propositions for an effective strategy are made.

AIDS Dementia Complex↗
PubMed2000

The cerebral hemodynamics of repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective in the treatment of affective disorders. However, only little is known about hemodynamic physiological and safety aspects of this method. We studied the cerebral hemodynamics as measured by transcranial Doppler sonography in 20 healthy subjects during different rTMS procedures. Mean cerebral blood flow velocity (CBFV), pulsatility index (PI), and oxygen consumption were recorded continuously and averaged directly after the rTMS procedure. RTMS did not influence blood pressure, pulse rate, or blood oxygenation. There was a maximal increase of CBFV in the middle cererbal artery (MCA) of 3.6% and 5.6% during 10 Hz and 20 Hz stimulation, respectively. This increase was only seen on the stimulated left hemisphere. The PI remained unchanged during the whole procedure. It is likely that the increase of CBFV is due to dilatation of the small resistance vessels rather than due to vasoconstriction of the MCA. In terms of cerebral hemodynamics, rTMS is a safe and well-tolerated technique with a lower increase of CBFV than that seen in electroconvulsive therapy.

Adult↗
PubMed2000

Changes of the neurotransmitter serotonin but not of hormones during short time music perception.

We studied the impact of the perception of pleasant and unpleasant music, as rated by healthy subjects with a psychometric scale, on the hormones prolactin and ACTH. In addition, the neurotransmitter serotonin (5-HT) was studied using the platelet model for central neurotransmission of 5-HT. We did not observe any significant changes of prolactin and ACTH during the perception of different kinds of music. The 5-HT content of platelets, however, was higher during the perception of pleasant music as compared to the perception of unpleasant music indicating an increased release of 5-HT during unpleasant music (748 ng/10(9) platelets vs. 699 ng/10(9) platelets; p<0.014). The difference of the 5-HT level was significantly correlated to the score of unpleasantness as rated by the subjects. Our data suggest that perception of unpleasant music induces increased release and decreased peripheral and possibly also central intracellular content of 5-HT.

Adrenocorticotropic Hormone↗