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Biomedical subjects

T Becker

Publications and source records attributed to T Becker.

At least 19 recordsLinked to original sources

Reduced echogenicity of brainstem raphe specific to unipolar depression: a transcranial color-coded real-time sonography study.

Echogenicity of the brainstem raphe was assessed in patients with major depression, bipolar affective disorders, and schizophrenia and compared with healthy adults employing transcranial color-coded real-time sonography. Forty probands were enrolled in each group. A highly significant reduction in raphe echogenicity was detected only in patients suffering from major depression. Echogenicity of the raphe was independent of age or sex and did not correlate with severity of the depressive syndrome or patient state. These findings are suggestive of structural desintegration of the brainstem raphe in unipolar depression, an anatomical region assumed to be a biological focus in the pathogenesis of depressive syndromes.

Adult

The corpus callosum in communicating and noncommunicating hydrocephalus.

To investigate morphological changes in the corpus callosum in hydrocephalus and to correlate them with clinical findings we studied sagittal T2*-weighted cine MR images of 163 patients with hydrocephalus. The height, length and cross-sectional area of the corpus callosum were measured and related to the type of cerebrospinal fluid flow anomaly and to clinical features, especially dementia. With expansion of the lateral ventricles the corpus callosum showed mainly elevation of its body and, to a lesser degree, increase in length. Upward bowing was more pronounced in noncommunicating than in communicating hydrocephalus. Dorsal impingement on the corpus callosum by the free edge of the falx correlated with the height of the corpus callosum. Cross-sectional area did not correlate with either height, length or impingement; it was, however, the strongest anatomical discriminator between demented and nondemented patients. The area of the corpus callosum was significantly smaller in patients with white matter disease. Our findings suggest that, due to its plasticity, the corpus callosum can to some degree resist distortion in hydrocephalus. Dementia, although statistically related to atrophy of the corpus callosum, is possibly more directly related to white matter disease.

Case-Control Studies

Correlation of cerebral blood flow and MCA flow velocity measured in healthy volunteers during acetazolamide and CO2 stimulation.

The assessment of the cerebrovascular reserve capacity (RC) has become a widely used tool in the management of cerebrovascular disease. Discrepancies become obvious, however, if results obtained with different methods are compared. Aim of the present study, therefore, was to compare blood velocity and cerebral perfusion data in the same group of healthy test persons. In 32 volunteers regional cerebral blood flow (rCBF) was measured with the 133Xe-inhalation method. F1 as grey matter flow and the initial slope index (ISI) were computed. Simultaneously flow velocity in the middle cerebral artery (VMCA) was assessed by transcranial Doppler sonography (TCD). Measurements were performed in the resting state, during inhalation of 7% CO2 and after 1 g acetazolamide. Baseline VMCA was 62.38 +/- 16.1 cm/s, 90.84 +/- 23.85 cm/s during hypercapnia and 84.91 +/- 24.54 cm/s after acetazolamide. There was no significant change of baseline or stimulated values with age. F1 rose from baseline 76.25 +/- 12.48 ml/100 g/min to 103.90 +/- 14.6 ml/100 g/min in hypercapnia and to 98.4 +/- 14.9 ml/100 g/min after acetazolamide. The baseline F1 values and the response to CO2 decreased with age (p = 0.01) whereas for the acetazolamide reaction an age dependency could not be proven. ISI baseline values (41.5 +/- 6.1 ml/100 g/min) as well as those found after CO2 or acetazolamide decreased significantly with age. In hypercapnia changes of F1 and ISI were not too well related with changes of VMCA (F1: r = 0.599; ISI: r = 0.473), but better during acetazolamide exposure (F1: r4 = 0.715; ISI: r = 0.522). The age dependency of resting and stimulated values has to be considered when assessing the reserve capacity. There is a correlation between changes of the perfusion and flow parameters in healthy individuals which, however, may be worse in cerebrovascular disease.

Acetazolamide

Lilliputian and negative hallucinations in a patient with probable encephalomyelitis disseminata.

A patient who showed Lilliputian hallucinations and negative hallucinations in the course of probable disseminated encephalomyelitis is described. At the age of 14 years the patient experienced a transient, flaccid paresis of the right leg. Eighteen years later she suddenly developed paranoid-hallucinatory symptoms accompanied by atypical visual hallucinations. She did not recover completely and until now she has suffered at least once every year from an episode with psychotic symptoms. During the most recent of these episodes, MRI revealed several disseminated supra- and infratentorial foci in the brain. Two of them, in the left cerebral peduncle and in the left occipital white matter are discussed as the cause of her visual hallucinatory symptoms.

Adult

Target-induced neurogenesis in the leech CNS involves efferent projections to the target.

During a critical period in leech embryogenesis, the sex nerves that connect the 5th and 6th midbody ganglia (MG5 and MG6) to the primordium of the male sexual organ carry a spatially localized signal that induces the birth of several hundred neurons specific to these ganglia. We examined particular cellular elements (afferents, efferents, non-neuronal components) within these nerves as potential conveyors of the inductive signal. We show that axons of peripheral sensory neurons in the male genitalia travel along the sex nerves and into MG5 and MG6, but reach the CNS after the critical period has elapsed and cannot, therefore, be involved in the induction. Of the six sex nerves, four contain non-neuronal cells that span the entire distance between the male genitalia and the sex ganglia. However, when male genitalia were transplanted to ectopic locations close to MG6, induction occurred frequently but only in MG6, mediated by ectopic nerves that do not contain these cells. Thus, non-neuronal cells specific to the normal sex nerves are not necessary for induction. In addition, dye injections into the target during the critical period failed to reveal migrating cells in the sex nerves that could convey the inductive signal to the CNS. Finally, we show that 11 pairs of central neurons in each ganglion project to the male organ early during the critical period. In the adult, at least 3 additional pairs of neurons in MG6 also innervate this target. We conclude that the only components of the sex nerves that connect the sex ganglia to the target during the critical period that could be associated with induced central mitogenesis are the axons of central neurons that innervate the male genitalia.

Animals

Omeprazole/amoxicillin versus triple therapy for Helicobacter pylori in duodenal ulcer disease: two-year follow-up of a prospective randomized study.

The present study was designed to compare the efficacy and tolerability of triple therapy and dual therapy for Helicobacter pylori in duodenal ulcer patients and to evaluate the long-term clinical course of ulcer disease. Forty duodenal ulcer patients with proven H. pylori infection were enrolled into the study and randomly treated with either triple therapy consisting of bismuth subsalicylate, metronidazole and tetracycline plus ranitidine or with dual therapy comprising omeprazole and amoxicillin. Patients were investigated clinically and endoscopically including assessment of H. pylori infection by means or rapid urease test, culture, histology and urea breath testing 4 weeks after cessation of eradication therapy, in 1-year intervals and when dyspeptic symptoms recurred. One patient of each group was lost during follow-up. H. pylori infection was cured by triple therapy in 84.2% and by dual therapy in 78.9% (p = 1.00). During follow-up, all patients with cure of H. pylori infection (n = 31) remained in stable remission with respect to duodenal ulcer disease, while 6 out of 7 patients persistently infected with H. pylori developed an ulcer relapse (p < 0.001). One patient with cured infection had had an episode of dyspeptic symptoms requiring pharmacotherapy and in another 3 patients mild refluxesophagitis without necessity of medical treatment had been detected on the occasion of a scheduled endoscopy. In the short-term, cure of the infection resulted in a marked reduction of the degree of antral gastritis and in a loss of activity in all but one patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Short-term triple therapy with pantoprazole, clarithromycin and metronidazole in eradication of Helicobacter pylori].

In a prospective study, thirty consecutive patients presenting with either H.pylori positive (histology and/or culture) ulcer disease (n = 17; acute ulcer: n = 11) or functional dyspepsia (n = 13) were treated over one week with pantoprazole 40 mg bd, clarithromycin 250 mg bd and metronidazole 400 mg bd. Four weeks after discontinuation of the study medication H.pylori eradication was assessed by means of an urease test, culture and histology. One patient had to be withdrawn from the study after one day because of a concomitant infectious disease requiring long-term antibiotic treatment. Another patient refused the final follow-up endoscopy. 28 patients completed the study without contravening the protocol. H.pylori infection was eradicated in 24 out of 28 patients (eradication rate: 86%; 95%-confidence interval: 57%-96%). Cure of bacterial infection was more frequently obtained in ulcer patients as compared to patients suffering from functional dyspepsia (94% vs 75%; p = 0.28). In 2 patients, treatment failure was associated with pretherapeutic resistance of H. pylori to either clarithromycin or metronidazole. Without antiulcer treatment beyond eradication therapy, ulcer healing was endoscopically confirmed after 5 weeks in 9 out of 10 patients available for follow-up (healing rate: 90%; 95%-confidence interval: 56%-100%). Seven patients reported mild adverse events that did not lead to discontinuation of the study medication (rate: 23%; 95%-confidence interval: 10%-42%). After cure of the infection, histology demonstrated a statistically highly significant improvement (p < 0.001) of both grade and activity of antrum and body gastritis.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Pyridinylmethylsulfinylbenzimidazoles

[Zolpidem dependence and depression in the elderly].

In a 75 years-old patient with chronic senile depression criteria of zolpidem dependency were fulfilled. There was no history of benzodiazepine or alcohol abuse. Positive psychotropic effects were emphasized by the patient who spread intake over the day.

Aged

[Closure of large psychiatric hospitals in England: evaluation by the TAPS project--a review of the literature].

The TAPS study evaluates the closure of two Greater London mental hospitals. Beginning in 1985, one-year and five-year follow-up compared successive cohorts of long-stay patients discharged to the community (leavers) with groups of matched long-stay patients who stayed in hospital. Some psychopathological symptoms improved in discharged patients, some did not. Mortality, patient vagrancy and delinquent behaviour did not increase in leavers. Patient autonomy, social networks and patient satisfaction favoured out-patient provision of care as compared to continuing in-patient care.

Community Mental Health Services

[The status of transcranial color-coded real time ultrasound in diagnosis of cerebral lesions].

Transcranial color-coded real-time sonography (TCCS) combines transcranial Doppler sonography and color-coded B-mode scanning of the brain parenchyma and cerebral vessels. This technique is not invasive and a broad spectrum of intracerebral lesions such as vascular lesions (ischemic stroke and intracerebral hemorrhage, aneurysms, arteriovenous malformations, arteriosclerotic vascular degeneration) and parenchymal lesions (brain tumors, degenerative and neuropsychiatric disorders) can be disclosed. Compared with MRI and CT, the ultrasound system is movable. Thus, it can be used easily in emergency rooms and intensive care units. In addition, TCCS can disclose new insights into the pathophysiology of disorders of the CNS, as in neuropsychiatric diseases. Ultrasound contrast agents improve the depiction of intracranial vessels. The pathology of the venous system can be identified.

Adult

One-week low-dose triple therapy for the eradication of Helicobacter pylori infection.

OBJECTIVE: To evaluate the efficacy and safety of two 1-week low-dose triple therapy regimens for the treatment of Helicobacter pylori infection. PATIENTS AND METHODS: Eighty patients with H. pylori infection and peptic ulcer disease (n = 64) or functional dyspepsia (n = 16), with similar demographic and clinical characteristics, were treated for 1 week with either omeprazole 20 mg once in the morning and clarithromycin 250 mg and metronidazole 400 mg twice daily (OCM; n = 40) or with omeprazole 20 mg once in the morning and clarithromycin 250 mg and tetracycline 500 mg twice daily (OCT; n = 40). H. pylori infection was assessed by urease test, culture and histology performed before and 4 (or more) weeks after cessation of the eradication therapy. RESULTS: H. pylori infection was treated successfully in 38 out of 40 patients by OCM and in 26 out of 40 patients by OCT (95 versus 65%, respectively; P = 0.0015). The OCM regimen was well tolerated in all patients except for one who complained of epigastric pain. Three patients on the OCT regimen reported side effects (abdominal pain, diarrhoea, pruritus), two of whom discontinued the study medication after 1 day. CONCLUSIONS: The 1-week low-dose triple therapy comprising omeprazole, clarithromycin and metronidazole was highly effective in eradicating H. pylori and was well tolerated. The replacement of metronidazole by tetracycline resulted in a significant decrease in the eradication rate.

Adult

Changes of pharmacological properties of (1S,3R)-ACPD-sensitive glutamate binding sites in developing mouse cerebellum.

Autoradiography of [3H]glutamate binding to mouse cerebellar sections was used to study the distribution of (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-((1S,3R)-ACPD) sensitive [3H]glutamate binding sites and the sensitivity of these sites to drugs preferentially acting on one or few types of the metabotropic receptor family. The inhibitory effect of (1S,3R)-ACPD on [3H]glutamate binding and its estimated inhibition constant showed the presence of a different global metabotropic receptor population according to the region considered. During ontogeny, the (1S,3R)-ACPD binding site density increased in the molecular layer (ML), in contrast it decreased in the internal granular layer (IGL) and the deep cerebellar nuclei (DCN). In addition, different sensitivities to (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG), (S)-4-carboxyphenylglycine (4-CPG), (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine (L-CCG-I) and L-2-amino-4-phosphonobutyric acid (L-AP4) were demonstrated according to the region and the age. In the DCN, the high (1S,3R)-ACPD binding site density at PND 10 seems to be also sensitive to L-CCG-I but not to MCPG, 4-CPG or L-AP4. In the ML, the MCPG-, the 4-CPG- and the L-AP4-sensitive [3H]glutamate binding sites appeared during ontogeny and the L-CCG-I-sensitive [3H]glutamate binding sites were already present at PND 10. In the IGL, L-CCG-I-sensitive binding sites disappeared in contrast to the L-AP4-sensitive binding sites which appeared during development even if the total (1S,3R)-ACPD binding site density was relatively weak in the adults. These results all reflected the multiplicity of the receptor subtypes included in the cerebellar metabotropic component.

Aminobutyrates

An automatic dehydrogenase-based flow-injection system: application for the continuous determination of glucose and lactate in mammalian cell-cultures.

A concept for the development of an automatic flow-injection analyzer with integrated dehydrogenase columns and its application in the control of industrial processes is presented. The system is based upon a kernel consisting of a nested-loop injection unit, pumps for the filling of the injection loops and the transport of buffer and values for switching on the one hand between sample and standard solutions and on the other hand between different enzyme columns. A Microsoft Windows 3.x application 'WIN-FIA' controls interactively the whole system and can be easily adapted to a specific solution of an analytical problem. As an example, the flow-injection system was used for the continuous determination of glucose and lactate, using glucose dehydrogenase (GDH) and lactate dehydrogenase (LDH) as indicator enzymes, in a mammalian cell-culture fermentation process. The resulting concentration values are in good agreement with those obtained by discontinuously taken standard spectrophotometric enzyme assays.

Animals

S100P, a novel Ca(2+)-binding protein from human placenta. cDNA cloning, recombinant protein expression and Ca2+ binding properties.

A novel member of the S100 protein family, present in human placenta, has been characterized by protein sequencing, cDNA cloning, and analysis of Ca(2+)-binding properties. Since the placenta protein of 95 amino acid residues shares about 50% sequence identity with the brain S100 proteins alpha and beta, we proposed the name S100P. The cDNA was expressed in Escherichia coli and recombinant S100P was purified in high yield. S100P is a homodimer and has two functional EF hands/polypeptide chain. The low-affinity site (Kd = 800 microM), which, in analogy to S100 beta, seems to involve the N-terminal EF hand, can be followed by the Ca(2+)-dependent decrease in tyrosine fluorescence. The high-affinity site, provided by the C-terminal EF hand, influences the reactivity of the sole cysteine which is located in the C-terminal extension (Cys85). Binding to the high-affinity site (Kd = 1.6 microM) can be monitored by fluorescence spectroscopy of S100P labelled at Cys85 with 6-proprionyl-2-dimethylaminonaphthalene (Prodan). The Prodan fluorescence shows a Ca(2+)-dependent red shift of the maximum emission wavelength from 485 nm to 502 nm, which is accompanied by an approximately twofold loss in integrated fluorescence intensity. This indicates that Cys85 becomes more exposed to the solvent in Ca(2+)-bound S100P, making this region of the molecule, the so-called C-terminal extension, an ideal candidate for a putative Ca(2+)-dependent interaction with a cellular target. In p11, a different member of the S100 family, the C-terminal extension which contains a corresponding cysteine (Cys82 in p11), is involved in a Ca(2+)-independent complex formation with the protein ligand annexin II. The combined results support the hypothesis that S100 proteins interact in general with their targets after a Ca(2+)-dependent conformational change which involves hydrophobic residues of the C-terminal extension.

Amino Acid Sequence

Protein-protein interaction studied by site-directed mutagenesis. Characterization of the annexin II-binding site on p11, a member of the S100 protein family.

p11, a member of the S100 protein family, forms a stable heterotetrameric complex with annexin II. The p11-binding site of annexin II resides in the N-terminal 14 residues, which form an amphiphatic alpha-helix with the hydrophobic face representing the contact site for p11 (Johnsson, N., Marriott, G., and Weber, K. (1988) EMBO J. 7, 2435-2442). We show that a corresponding peptide can be used to purify recombinant p11 by affinity chromatography. To map the annexin II-binding site on p11, we have produced progressively truncated p11 derivatives by site-directed mutagenesis. Our analysis reveals that a highly hydrophobic region between residues 85 and 91 is indispensable for annexin II-binding. It is located in the C-terminal extension, following the second distorted EF-hand. Using a series of single amino acid replacements, we have identified individual hydrophobic residues, which seem to represent contact points for annexin II. Most notably, substitution of tyrosine 85 or phenylalanine 86 by alanine drastically reduces the affinity of p11 for annexin II, whereas replacement of these residues by tryptophan has no or only a marginal effect. Thus, hydrophobic side chains on both annexin II and p11 are involved in complex formation.

Amino Acid Sequence

Neurological long-term follow-up in left atrial myxoma: are late complications frequent or rare?

Neurological manifestations were analysed in 13 patients with left atrial myxoma confirmed by histological study. In this group, 6 patients had neurological complaints at initial presentation, 5 had cardiac symptoms, and 4 patients presented with signs of systemic disease. CT was performed in 10 and MRI in 7 patients. There were signs of ischaemic or haemorrhagic infarction (6 of 12) and one lesion suggestive of myxoma metastasis; other findings mainly comprised non-specific white matter lesions revealed by MRI. Neurological follow-up 0.5-8 years after tumour resection revealed no delayed neurological complications, follow-up CT and MRI findings were not suggestive of lesions acquired after operation. It is suggested that this rare condition of cardiac myxoma should be suspected in young patients with CNS symptoms or signs lacking cerebrovascular or cardiovascular risk factors and should be included in the differential diagnosis of vasculitis. With timely diagnosis and resection of the cardiac tumour the long-term prognosis can be considered improved.

Adult