[Somatoform disorders without findings--modern syndromes].
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Biomedical subjects
Publications and source records attributed to A Barth.
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Persisting perfusion defects may still be found in pulmonary perfusion scintigraphy months or years after pulmonary embolism. The aim of this study was to investigate the rate of persisting perfusion defects and the pattern of scintigraphic follow-up of patients after pulmonary embolism. Only those patients were included into our study who received pulmonary perfusion scintigraphy between 1991 and 1999, and who had perfusion defects including at least one whole segment. These perfusion defects were considered as persisting perfusion defects if unchanged over at least 1 year. From 3640 patients examined, 451 (12.4%) had perfusion defects meeting the criteria of this study. Of those, 129 (28.6%) received a scintigraphic follow-up. In 62 patients (48.1%), a reperfusion of the defects was found. In 38 patients (29.5%), the defects persisted within a follow-up period of up to 12 weeks. However, no pulmonary perfusion scintigraphy was performed thereafter. Out of the 129 patients receiving a scintigraphic follow-up, only 29 (22.5%) had a follow-up over more than 1 year, 19 of those had persisting perfusion defects. It is concluded that our data show an inadequate scintigraphic follow-up of patients with pulmonary embolism which may lead to unnecessary anticoagulant treatment if persisting perfusion defects are misinterpreted as fresh pulmonary embolism. In many cases, there was no further follow-up even if reperfusion of the defects was lacking in early follow-up.
Frozen semen from a control bull (C: 89% morphologically normal sperm) and two bulls with acrosomal defects (K1: 92% flattened acrosomes; K2: 82% indented acrosomes) were used to investigate the fertilizing ability of bull sperm with flattened or indented acrosomes. In experiment 1, frozen-thawed sperm were evaluated for acrosomal integrity with fluorescent microscopy. In experiment 2, proteolytic activity of the acrosomal contents of sperm was evaluated through a gelatin digestion assay. In experiment 3, an IVF test system was used to determine the ability of sperm with flattened or indented acrosomes to bind to bovine oocytes and penetrate the zona pellucida. In experiment 4, IVM zona-free bovine oocytes (ZFO) were fertilized and examined to evaluate sperm chromatin decondensation. In experiment 1, bulls K1 and K2 had a lower proportion of sperm with intact acrosomes (0 and 13.6 +/- 4.5%, respectively) than bull C (30.2 +/- 5.6%) after 2h of incubation. In experiment 2, the proportion of sperm with proteolytic activity, as indicated by gelatin digestion around sperm heads, did not differ among bulls (C: 55%, n=410; K1: 43%, n=426; K2: 48%, n=324). In experiment 3, a lower proportion of sperm with flattened (K1) or indented acrosomes (K2) bound to oocytes than sperm from the control bull, C. The percentage of zona penetrated (55%, n=20; 13%, n=23; 4%, n=25) and the mean (+/- S.E.M.) number of sperm penetrating these zona pellucida (19.7 +/- 2.5; 6.9 +/- 1.0; and 2.6 +/- 0.5) was higher (P<0.05) for bull C than for bulls K1 or K2, respectively. In experiment 4, the percentage of ZFO penetrated (95%, n=20; 52%, n=30; 30%, n=33) and the mean (+/- S.E.M.) number of sperm with chromatin decondensation (7.8 +/- 1.6; 0.8 +/- 0.2; and 0.3 +/- 0.1) were also higher (P<0.05) for the control bull, C than for bulls K1 or K2, respectively. Results suggest that although sperm with the flattened or indented acrosomes had a tendency to undergo spontaneous acrosome reaction on incubation after thawing, the proteolytic activity of the acrosomal contents appeared to be normal. Sperm with the flattened or indented acrosomes also appeared to have a reduced ability to fuse with oolemma as demonstrated by confocal microscopy. This would impair the ability to penetrate ooplasm and undergo sperm chromatin decondensation.
As part of the SENTRY Antimicrobial Resistance Surveillance Program, a total of 4998 strains of enterococci isolated from 1997 to 1999 were processed. The occurrence of enterococcal infections by species and site of infection was analyzed, as were the occurrence of vancomycin-resistant enterococci (VRE) and their resistance phenotypes and genotypes. Trends in antimicrobial susceptibility to a variety of agents (including experimental compounds) were also reported. Enterococci accounted for >9% of isolates from all bloodstream infections (BSIs) in North America. Ampicillin was active against strains from Latin America and Europe but not against those from the United States and Canada. US isolates were considerably more resistant to vancomycin (17% resistant strains in 1999) than were those from patients in the rest of the world. The highest proportion of VRE was observed among BSI isolates (81.7%). Quinupristin-dalfopristin, chloramphenicol, and doxycycline were the most active agents tested against VRE. The results of this study confirm the worldwide trend in increasing occurrence of enterococci and the emerging pattern of antimicrobial resistance among such isolates.
HISTORY AND ADMISSION FINDINGS: 3 years ago, a 63-year-old man underwent laparotomia due to clinical signs of acute abdominal pain. The anemia was treated with erythrocyte concentrates. Several weeks before the current admission to our outpatient department, the patient was again hospitalized because of acute abdominal pain and anemia. The patient was then transferred to the University clinic for further medical tests. INVESTIGATIONS: In addition to a normocytic anemia, a secondary porphyria was found. Further medical tests demonstrated lead poisoning. DIAGNOSIS, TREATMENT AND COURSE: Initially, the cause of the lead poisoning remained unclear because the patient had reported neither an occuppational nor an environmental exposure to lead. Finally, a prescription-prepared ointment was evaluated, which the patient had applied to his feet and lips over the past 3 years. CONCLUSION: Lead poisoning can be found outside the realm of occupational exposure; therefore, the knowledge of lead poisoning is still important.
This paper reviews state-of-the-art reaction-induced infrared difference spectroscopy of proteins. This technique enables detailed characterization of enzyme function on the level of single bonds of proteins, cofactors, or substrates. The following methods to initiate a reaction in the infrared sample are discussed: (i) light-induced difference spectroscopy, (ii) attenuated total reflection with buffer exchange, (iii) the infrared variant of stopped and continuous flow, (iv) temperature and pressure jump, (v) photolytical release of effector substances from caged compounds, (vi) equilibrium electrochemistry, and (vii) photoreduction. Illustrating applications are given including hot topics from the fields of bioenergetics, protein folding, and molecule--protein interaction.
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Concretism is considered an important aspect of schizophrenic thought disorder. Traditionally it is measured using the method of proverb interpretation, in which metaphoric proverbs are presented with the request that the subject tell its meaning. Interpretations are recorded and scored on concretistic tendencies. However, this method has two problems: its reliability is doubtful and it is rather complicated to perform. In this paper, a new version of a multiple choice proverb test is presented which can solve these problems in a reliable and economic manner. Using the new test, it is has been shown that schizophrenic patients have greater deficits in proverb interpretation than depressive patients.
Carps, both sexes, 3 years old, weighing about 1 kg, and tenches of both sexes, 6 years old, weight about 250 g, were caught from a Thuringian lake without industrial pollution in November 1995 (fish without food uptake, water temperature at about 10 degrees C) and kept for 2 weeks in basins with clean water and addition of 0, 0.1, 1.0 or 10.0 mg/l phenobarbital-Na (PB). The concentration of PB was controlled during and at the end of the exposure period. The animals were fed pellets, but no food uptake was observed. After 24-48 h in fresh water the fish were sacrificed and the following hepatic parameters were immediately determined biochemically: monooxygenase functions: cytochrome P450 (P450) content, ethylmorphine N-demethylation (EN), ethoxycoumarin O-deethylation (ECOD), ethoxyresorufin O-deethylation (EROD), 7-benzyloxy-4-methyl-coumarin O-debenzylation (BCDB); oxidase function indicators: microsomal Fe2+/NADPH dependent hydrogen peroxide formation (H2O2), microsomal Fe2+/NADPH dependent luminol and lucigenin amplified chemiluminescence (LMCL, LCCL), microsomal Fe2+/NADPH dependent lipid peroxide formation (LPO); oxidative state: lipid peroxidation products (TBARS) and GSH and GSSG. Additionally, the expression of three P450 isoforms, 1A1, 2B and 3A, was assessed immunohistochemically in tissue samples from brain, gill, heart, spleen, liver, gut and ovary of both fish species and in kidney of tenches. PB did not influence body or liver weights, but increased liver P450 concentration in both species by 50-100%, though not significantly. Carp: PB increased both EN and EROD significantly, but not ECOD and BCDB; H2O2 and TBARS were enhanced significantly. LPO, LMCL and LCCL were not significantly influenced. Tench: PB increased all monooxygenase reactions (EN, ECOD, BCDB and EROD), though only significantly ECOD; H2O2 was elevated only after treatment with 0.1 mg/l PB, whereas LPO was decreased (!) after treatment by all three concentrations, though significantly only after 1.0 mg/l PB. LMCL was depressed (not significantly), but LCCL increased 5fold. TBARS were significantly enhanced. P450 1A1 subtype expression was concentration dependently elevated by PB in gill and liver of both fish and in the heart and kidney of tenches, P450 2B and 3A isoforms expression was induced in brain, gill, heart, liver and gut of both fish and in the kidney of tenches. In summary, the increased activities of the monooxygenase reactions tested and the elevated expression of all three P450 isoforms investigated in certain tissues indicate an induction of the P450 families 1, 2 and 3 by PB in fish.
Most of the completely sequenced prokaryotic genomes contain genes of potassium channel homologues, but there is still not much known about the role of these proteins in prokaryotes. Here we describe the large-scale overproduction and purification of a prokaryotic voltage-gated potassium channel homologue, Kch, from Escherichia coli. After successful overproduction of the protein, a specific increase in the potassium permeability of the cells was found. Kch could be purified in large amounts using classical purification methods to prevent aggregation of the protein. The physiological state of the protein was revealed to be a homotetramer and the protein was shown to be localized to the cytoplasmic membrane of the cells. In the course of the localization studies, we found a specific increase in the density of the cytoplasmic membrane on Kch production. This was linked to the observed increase in the protein to lipid ratio in the membranes. Another observed change in the membrane composition was an increase in the cardiolipin to phosphatidylglycerol ratio, which may indicate a specific cardiolipin requirement of Kch. On the basis of some of our results, we discuss a function for Kch in the maintenance of the membrane potential in E. coli.
Sulfamate substitution (-O-SO2-NH2) at carbon atom 3 of the steroid skeleton leads to orally active prodrugs of estrogens with much higher systemic, but lower hepatic, estrogenic activity than their parent steroids. This dissociation is achieved by first passage through the liver in erythrocytes, followed by systemic hydrolysis which releases the 'parent' estrogen. In the rat, orally administered tritiated estradiol sulfamate, unlike estradiol, appears in the circulation at high concentrations. At Cmax, approximately one third of the administered dose forms a depot in the circulation (98% in erythrocytes, 2% in plasma). Significant estradiol, estrone and estrone sulfate concentrations were recorded in plasma during depletion of the red blood cell pool. Estradiol sulfamate (J995) has no estrogen receptor affinity per se or estrogenic activity in vitro ( i.e. without hydrolysis). Its oral uterotropic activity in rats is approximately 100 times greater than that of estradiol, however, its hepatotropic activity is only marginally elevated. These functions include bile secretion, the secretion of angiotensinogen, lipoproteins (total and high-density lipoprotein cholesterol) and insulin-like growth factor I (IGF-I). Orally administred estradiol sulfamate led to systemic estrogenic effects without significant hepatic responses, whereas estradiol and other 'conventional' estrogens exerted parallel systemic and hepatic estrogenic effects. Sulfamate technology represents an approach to the use of natural estrogens for fertility control and hormone replacement therapy in both genders. In this context, reduced effects on hemostatic factors, angiotensinogen, bile and IGF-I secretion seem the most important aspects. In addition, blood concentrations of estrogens are less variable than with conventional estrogens.
The goal of this study was to collect prospective longitudinal information on the development of an epidemiologically defined cohort of patients with Tourette syndrome. These data may improve prognostic understanding of the condition. This information will also be important for specification of an adult phenotype for genetic marker studies. A prospective longitudinal cohort study was conducted. Fifty-four of 73 patients from our 1986 prevalence study of Tourette syndrome in North Dakota school-aged children were eligible for inclusion. The subjects were diagnosed in 1984 and 1985. We were able to interview 39 of 54 eligible patients for 507 person-years of follow-up. For the cohort, tic severity declined by 59%, global assessment of functioning improved by 50%, and the average number of comorbidities decreased by 42%. Forty-four percent of patients were essentially symptom free at follow-up. Only 22% were on medication as adults. Tourette syndrome is a developmental neuropsychiatric disorder with a long-term course that is favorable for most patients. Males demonstrated substantially more variability in improvement but overall demonstrated more improvement than females.
Regulatory peptides are small, readily diffusable and potent natural substances with a wide spectrum of receptor-mediated actions in humans. High affinity receptors for these peptides are (over-) expressed in many neoplasms, and these receptors may represent, therefore, new molecular targets for cancer diagnosis and therapy. This review aims to give an overview of the peptide-based radiopharmaceuticals which are presently already commercially available or which are in advanced stages of their clinical testing so that their broader availability is anticipated soon. Physiologically, these peptides bind to and act through G protein-coupled receptors in the cell membrane. Historically, somatostatin analogs are the first class of receptor binding peptides having gained clinical application. 111In-DTPA-[D-Phe1]-octreotide is the first and only radiopeptide which has obtained regulatory approval in Europe and the United States to date. Extensive clinical studies involving several thousands of patients have shown that the major clinical application of somatostatin receptor scintigraphy is the detection and the staging of gastroenteropancreatic neuroendocrine tumors (carcinoids). In these tumors, octreotide scintigraphy is superior to any other staging method. However, its sensitivity and accuracy in other, more frequent neoplasms is limited. Radiolabeled vasoactive intestinal peptide (VIP) has been shown to visualize the majority of gastrointestinal adenocarcinomas, as well as some neuroendocrine tumors, including insulinomas (the latter being often missed by somatostatin receptor scintigraphy). Due to the outstanding diagnostic accuracy of the pentagastrin test in detecting the presence, persistence, or recurrence of medullary thyroid cancer (MTC), we postulated the expression of the corresponding (ie. cholecystokinin [CCK-] -B) receptor type in human MTC. This receptor is also widely expressed on human small-cell lung cancer. Indeed, 111In-labeled DTPA derivatives of gastrin showed excellent targeting of CCK-B receptor expressing tissues in animals and patients. A variety of further peptide-based radioligands, e.g. among many others, gastrin-releasing peptide/bombesin, neurotensin, substance-P, pan-somatostatin (somatostatin derivatives which bind to all five receptor subtypes) or glucagon-like peptide-1 (glp-1) analogs (the latter for the specific detection of insulinomas), is currently under development. Summarizing, radiolabeled regulatory peptides have opened new horizons in nuclear oncology for diagnosis (and potential internal radionuclide therapy). Future work will probably reveal a multitude of novel potentially clinically useful peptide-based radioligands.
BACKGROUND: The indications for carotid endarterectomy have been defined on the basis of several large prospective randomised trials. Today this operation is widely performed as primary and secondary stroke prevention in patients with high grade carotid artery stenosis. Permanent quality control of the surgical results is mandatory to ensure optimal stroke prevention and further reduce perioperative complications. METHODS: In this retrospective study we analyse the surgical results of 272 consecutive carotid endarterectomies performed in 260 patients with special emphasis on the prevention of intraoperative brain ischaemia. Patients were operated on in general anaesthesia and moderate hypothermia. Before clamping the arteries at the neck, a fast-acting barbiturate or propofol was administered intravenously to obtain burst suppression on the EEG. Transcranial Doppler sonography allowed continuous intraoperative monitoring of brain perfusion and detection of emboli. Intraoperative shunting was performed only when the collateral circulation was insufficient. RESULTS: The postoperative course was uneventful in 249 endarterectomies (91.5%). The internal carotid artery was sonographically recanalised at hospital discharge and at 6-week follow-up in all 249 cases. Ischaemic cerebral complications were observed in 7 patients (2.6%): minor reversible brain ischaemia in 4 (1.5%), and major brain ischaemia with infarction in 3 (1.1%). Three patients died in the perioperative period, representing a mortality rate of 1.1% in this series. The overall combined stroke and death rate was 3.7%. The combined major stroke and death rate was 2.2%. Various non cerebral complications occurred in 13 patients (4.8%). CONCLUSIONS: These results confirm that endarterectomy is a safe and efficient treatment for atherosclerotic carotid stenosis at the neck. Very low complication rates can be attained by non-invasive diagnostic methods combined with intraoperative monitoring of cerebral blood flow velocity. New upcoming endovascular therapies such as percutaneous angioplasty and stenting need to be compared with these current surgical results with regard not only to perioperative morbidity and mortality but also patency rate, restenosis, and intracerebral blood flow restoration.
Protein conformational changes triggered by molecule binding are increasingly investigated by infrared spectroscopy often using caged compounds. Several examples of molecule-protein recognition studies are given, which focus on nucleotide binding to proteins. The investigation of enzyme mechanisms is illustrated in detail using the Ca(2+)-ATPase of the sarcoplasmic reticulum membrane as an example. It is shown that infrared spectroscopy provides valuable information on general aspects of enzyme function as well as on molecular details of molecule-protein interactions and the mechanism of catalysis.
HISTORY AND REASON FOR ADMISSION: A 44-year-old man had anginal-like complaints. He was convinced that cardiac problems had been caused by electromagnetic fields. INVESTIGATIONS: Apart from hypertension and hyperlipidaemia there were no other significant findings. ECG, ergometry Holter-ECG were normal. EXPERIMENT: We tried to verify with a double-blind provocation test if the patient's complaints had been caused by electromagnetic fields. The patient was exposed to an electric instrument without being aware whether it was switched on or off. He was questioned about his perception of the presence of an electric current. CONCLUSION: The results of the test showed that there was no causal relation between the patient's angina-like-symptoms and electromagnetic fields. The phenomenon of electrosensitivity was probably caused by psychological mechanisms.
Inhibition of oestrone sulphatase followed by oestrogen removal from tumour cells may be a new form of endocrine therapy of breast cancer in women. We investigated the inhibitory effect of the subchronic administration of oestrone-3-O-sulphamate (EMATE), a steroid sulphatase inhibitor, to ovariectomized rats, to evaluate this method for testing new nonsteroidal inhibitors. EMATE in DMSO was administered both orally and subcutaneously (s.c.) for 7 days at doses of 0.5 and 2.5 mg/kg. In addition the rats were injected s.c. with 0.5 mg oestrone sulphate/kg 26 and 2 h before decapitation under ether anaesthesia. Oestrone sulphatase activity (ESA) was measured radiometrically using [3H]oestrone sulphate as substrate for desulphuration in white blood cells, liver homogenate, microsomes and spleen homogenate. ESA in liver microsomes was found to be nearly 40 times higher than in white blood cells while in spleen ESA was nearly half of that found in liver homogenates and white blood cells. ESA can be inhibited by EMATE down to 50-1.5% of control activity depending on the dose and administration route. The inhibition was in the order, liver homogenate < spleen < liver microsomes < white blood cells, and was more pronounced after s.c. administration of the inhibitor than after oral administration. Ovariectomy was found to be not necessary for oestrone sulphatase-inhibiting studies. Two sequential s.c. injections of oestrone sulphate enhanced the enzyme activities significantly in liver and white blood cells, but not in spleen. In conclusion, white blood cells and liver microsomes of intact female rats can be used for ESA-inhibiting studies. Sulphate-conjugated oestrone can induce oestrone sulphatase in vivo in liver and white blood cells thereby enhancing oestrogen supply in the peripheral organs.
Carotid stenting is increasingly considered as treatment for carotid artery disease. A reliable noninvasive method is desirable for assessing the safety of the procedure. Diffusion-weighted MRI (DWI) is sensitive to early brain ischaemia which becoming widely available and might therefore serve this purpose. We prospectively studied 19 patients referred for investigation of carotid artery disease by echo-planar whole-brain DWI before and within 24 h of stenting. The images obtained at a high b value were examined by two independent blinded reviewers for new high-signal areas consistent with ischaemia. We found that 15 patients had no new changes after stenting. One patient showed enlargement of a posterior watershed lesion after the procedure, which correlated with an increase in neurological deficit. Three other patients had presumed small embolic infarcts on DWI; two were asymptomatic and one had weakness at the hand that corresponded to an embolic infarct with a lesion on DWI in the hand notch. There were no false- positive or -negative results on DWI, when compared to clinical findings. DWI is thus a new method that can demonstrate neurologically silent or asymptomatic infants. It can be used to help to assess the safety and efficacy of neurovascular intervention.