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Biomedical subjects

H Schmidt

Publications and source records attributed to H Schmidt.

At least 145 records · Page 8Linked to original sources

Isolation and characterisation of five neurotoxic and cardiotoxic polypeptides from the sea anemone Anthopleura elegantissima.

Five toxins (APE 1 to APE 5) of the sea anemone species Anthopleura elegantissima (Brandt) have been isolated from a toxic by-product fraction of its concentrated crude watery-methanolic extract, prepared previously for the isolation of a neuropeptide (the head-activator) by Schaller and Bodenmüller (Proc. Natl. Acad. Sci. USA 78 (1981) 7000) from 200kg sea anemones. Toxin purification was performed by desalting of the starting material by dialysis (MWCO 3500) against distilled water, anion exchange chromatography on QAE-Sephadex A25 at pH 8, twice gel filtration on Sephadex G50 m, repeated chromatography on QAE-Sephadex at pH 10 and chromatography on the cation exchanger Fractogel EMD SO(3)(-)-650 M.Final purification of the toxins was achieved by HPLC on MN SP 250/10 Nucleosil 500-5 C(18) PPN and MN SP 250/21 Nucleosil 300-7 C(18). Each toxin was composed of at least two isotoxins of which APE 1-1, APE 1-2, APE 2-1, APE 2-2 and APE 5-3 were isolated in preparative scale. With exception of APE 5-3 the sequences of the isotoxins have been elucidated. They resemble the 47 residue type-I long polypeptide toxins native to Anemonia sulcata (Pennant). All isotoxins paralyse the shore crab (Carcinus maenas) by tetanic contractions after i.m. application. The toxins modify current passing through the fast Na(+) channel in neuroblastoma cells, leading to delayed and incomplete inactivation. APE 1-1, APE 2-1 and APE 5-3 produce a positive inotropic effect in mammalian heart muscle, although they differ in potency. The order of potency is APE 2-1>APE 1-1>APE 5-3 (i.e. threshold concentrations are 1, 10 and 300nM, respectively). In addition, they enhance the spontaneous beating frequency in isolated right atria (guinea pig). The most potent cardiotoxic isotoxin is APE 2-1, its sequence is identical with that of AP-C, a toxin isolated and characterised previously by Norton et al. (Drugs and Foods from the Sea, 1978, University of Oklahoma Press, p. 37-50).LD50 APE 2-1:1 micro g/kg b.w. C. maenas (i.m.). LD50 APE 1-1:10 microg/kg b.w. C. maenas (i. m.). LD50 APE 5-3:50 microg/kg b.w. C. maenas (i.m.).

Animals↗

Pyrolysis of oil sludge in a fluidised bed reactor.

The oil sludge of tanker cleaning was pyrolysed in fluidised bed reactors. Three experiments were conducted in a laboratory plant and two on a technical plant. Separation of oil from the solids and distribution of the oil products were investigated at temperatures from 460 degrees C to 650 degrees C. Between 70% and 84% of the oil could be separated from the solids. Distribution of the oil products depended on the feed material and the pyrolysis conditions. The higher the temperature the more the oil was cracked into low boiling compounds. Under the conditions of pyrolysis carbon reduced gridiron to iron. Thus some solid fractions were pyrophoric and oxidised with high heat generation. Therefore the solid products have to be turned into inert substances. The fluidised bed pyrolysis is an adequate process to recycle oil sludge with high yields.

Carbon↗

Predictive laboratory diagnostics in oncology utilizing blood-borne cancer cells--current best practice and unmet needs.

The aim of laboratory diagnostics in oncology is to improve the clinical outcome of cancer by allowing earlier detection. Molecular knowledge of cancer should increase the number of risk and prognostic factors and will allow development of methods for detection and elimination of even very small tumors. Thus, the race for the specific tumor antigen in peripheral blood and the race for the blood-borne cancer cell happened simultaneously. The direct detection of the cells which have the highest probability to harbor all the properties mandatory to be life-threatening, conceivably metastatic, would be the most promising way to find the target structure of malignancy. Methods applying enrichment techniques based on density, morphology, tissue specific protein and tumor-associated protein detection enabled multi-parametric analysis of those blood-borne cancer cells. In exemplary studies it was demonstrated that the count of cell clusters positive for the tissue-specific proteins cytokeratin and prostate-specific antigen (PSA) from the peripheral blood of prostate cancer patients and a combination of a tissue-specific protein, a oncogenic receptor protein cytokeratin and p185(c-erbB-2) from the peripheral blood of breast cancer patients is related to the stage of the diseases. Breast cancer patients who presented with cytokeratin/p185(c-erbB-2) positive cell clusters showed a decrease of those cells under adriamycin adjuvant therapy. Nevertheless, additional molecular markers are required to characterize the functional properties of blood-borne cancer cells. Therefore, the genome of the cells can be investigated using a procedure for indirectly detecting aberrations of defined gene locations, i.e. multiplex microsatellite polymerase chain reaction. Up to now, the methods applied to the separation of blood-borne cancer cells are time-consuming and rather expensive. They consist of an initial enrichment step of density gradient centrifugation or buffy coat preparation followed by a specific isolation step using superparamagnetic microbeads coupled to antibodies, filter techniques or multi-parametric flow cytometry. Novel technologies have to be applied using miniaturization, integration and parallel-processing techniques based on those used in the computer industry to overcome the drawbacks.

Antigens, Neoplasm↗

Prevalence of left atrial chamber and appendage thrombi in patients with atrial flutter and its clinical significance.

OBJECTIVES: The study was done to assess the prevalence of left atrial (LA) chamber and appendage thrombi in patients with atrial flutter (AFl) scheduled for electrophysiologic study (EPS), to evaluate the prevalence of thromboembolic complications after transesophageal echocardiographic (TEE)-guided restoration of sinus rhythm and to evaluate clinical risk factors for a thrombogenic milieu. BACKGROUND: Recent studies showed controversial results on the prevalence of atrial thrombi and the risk of thromboembolism after restoring sinus rhythm in patients with AFl. METHODS: Between 1995 and 1999, patients with AFl who were scheduled for EPS were included in the study. After transesophageal assessment of the left atrial appendage and exclusion of thrombi, an effective anticoagulation was initiated and patients underwent EPS within 24 h. RESULTS: We performed 202 EPSs (radiofrequency catheter ablation, n = 122; overdrive stimulation, n = 64; electrical cardioversion, n = 16) in 139 consecutive patients with AFl. Fifteen patients with a thrombogenic milieu were identified. All of them had paroxysmal atrial fibrillation (AF). Transesophageal echocardiography revealed LA thrombi in two cases (1%). After EPS no thromboembolic complications were observed. Diabetes mellitus, arterial hypertension and a decreased left ventricular ejection fraction were found to be independent risk factors associated with a thrombogenic milieu. CONCLUSIONS: The findings of a low prevalence of LA appendage thrombi (1%) in patients with AFl and a close correlation between a history of previous embolism and paroxysmal AF support the current guidelines that patients with pure AFl do not require anticoagulation therapy, whereas patients with AFl and paroxysmal AF should receive anticoagulation therapy. In addition, the presence of clinical risk factors should alert the physician to an increased likelihood for a thrombogenic milieu.

Aged↗

Shiga-toxin-converting bacteriophages.

Shiga toxins (Stx) comprise a family of potent cytotoxins that are involved in severe human disease. Stx are mainly produced by Escherichia coli isolated from human and nonhuman sources, and by Shigella dysenteriae type 1. The genes encoding Stx are thought to be generally encoded in the genome of lambdoid prophages (Stx-converting bacteriophages; Stx phages). They share a unique position in the late region of the phage genome downstream of the late promoter PR'. This location suggests that expression of stx is controlled by a Q-like antiterminator. Therefore, induction of Stx-converting prophages appears to trigger increased production of Stx. Following induction, Stx phages can be transduced in vivo and in vitro into other bacteria. Stx phages play an important role in the expression of Stx and in lateral gene transfer and are therefore a contribution to the emergence of new Stx-producing E. coli (STEC) variants.

Bacteriophages↗

Responsiveness of subjective quality of life assessment in schizophrenic patients: a quasi-experimental pilot study.

Responsiveness of quality of life (QOL) assessments in chronic schizophrenic patients was investigated by a quasi-experimental pilot study. Satisfaction ratings were assessed over five time points with an externally imposed disturbing stimulus at the second time point. Despite a markedly high stability, the disturbance provoked a temporally limited decrease in QOL.

Chronic Disease↗

The structure of negative emotions in adolescents.

This study examined the structure of negative emotions in a sample of nonclinical adolescents, using an approach that exclusively relied on child self-report. A large sample of adolescents (N = 968) completed self-report questionnaires measuring symptoms of fear, anxiety, and depression. Confirmatory factor analysis provided support for the notion that fear, anxiety, and depression are distinct yet correlated components of negative emotions. This result is in agreement with recent empirical findings and current theoretical notions on the structure of negative emotions in children and should be taken as an encouragement for researchers to develop more specific measures for assessing fear, anxiety, and depression in children.

Adolescent↗

Retinal detachment and cataract, facial dysmorphism, generalized osteoporosis, immobile spine and platyspondyly in a consanguinous kindred--a possible new syndrome.

We report on a consanguineous family with 6 children (out of 7) affected by a spondylo-ocular syndrome. Clinical features include cataract, loss of vision due to retinal detachment, facial dysmorphism, facial hypotonia, normal height with disproportional short trunk, immobile spine with thorakal kyphosis and reduced lumbal lordosis. On ophthalmological examination of the index patient, a dense cataract and complete retinal detachment could be detected on the right eye. On the left eye, an absent lens nucleus was found, but no retinal detachment. On radiological examination, there was generalized moderate osteoporosis; the spine showed marked platyspondyly and the bone age was advanced. On laboratory investigations, a normal excretion of amino acids, mucopolysaccharides and oligosaccharides could be found. The phenotypical spectrum observed in the 6 affected individuals was rather uniform. The karyotype was normal in all affected children. This hitherto undescribed combination of oculo-skeletal symptoms shows most resemblance with connective tissue disorders, suggesting a range of candidate genes for mutation analysis.

Abnormalities, Multiple↗

Validity of wet-mount bacterial morphotype identification of vaginal fluid by phase-contrast microscopy for diagnosis of bacterial vaginosis in family practice.

The aim of this study was to determine the accuracy of a wet-mount bacterial morphology scoring (BMS) system and Nugent's Gram stain analysis for the diagnosis of bacterial vaginosis, using Amsel's criteria as the gold standard. The three diagnostic criteria were assessed independently The BMS diagnosis was based on a scoring system which weighed the number of small bacterial morphotypes regarded as typical of bacterial vaginosis against lactobacillary morphotypes in phase-contrast microscopy of wet-mount preparations. Three groups of non-pregnant women attending either because of vaginal discharge, other genitourinary symptoms, or for a routine check-up, and a group of pregnant women attending for antenatal care were studied. The diagnostic accuracy was measured by sensitivity, specificity, positive and negative predictive values, and likelihood ratio. The accuracy of the BMS diagnosis was substantially high in all of the examined groups (LR 15.4-20.3). The accuracy of the Gram stain diagnosis was lower (LR 7.6-10.9). In the total material, the accuracy of the BMS diagnosis was higher than that of the Nugent's Gram staining. Intra- and inter-observer reproducibility of all three criteria applied was high. We propose greater routine use of the new BMS diagnosis for point-of-care testing in family practice as well as in research and in microbiology laboratories.

Adult↗

N-acetylcysteine induces shedding of selectins from liver and intestine during orthotopic liver transplantation.

In orthotopic liver transplantation (OLT), N-acetylcysteine (NAC) reduces ischaemia/reperfusion (I/R) injury, improves liver synthesis function and prevents primary nonfunction of the graft. To further elucidate the mechanisms of these beneficial effects of NAC, we investigated influence of high-dose NAC therapy on the pattern of adhesion molecule release from liver and intestine during OLT. Nine patients receiving allograft OLT were treated with 150 mg NAC/kg during the first hour after reperfusion; 10 patients received the carrier only. One hour after reperfusion, samples of arterial, portal venous and hepatic venous plasma were taken and blood flow in the hepatic artery and the portal vein was measured. Absolute concentrations of sICAM-1, sVCAM-1, sP-selectin and sE-selectin were not markedly different. However, balance calculations showed release of selectins from NAC-treated livers as opposed to net uptake in controls (P < or = 0.02 for sP-selectin). This shedding of selectins might be a contributing factor to the decrease in leucocyte adherence and improved haemodynamics found experimentally with NAC-treatment.

Acetylcysteine↗

Comparative analysis of costs of total intravenous anaesthesia with propofol and remifentanil vs. balanced anaesthesia with isoflurane and fentanyl.

BACKGROUND AND AIM: We evaluated the costs and benefits of total intravenous anaesthesia compared with a balanced anaesthesia regimen. METHODS: One-hundred and twenty-four patients undergoing cataract surgery were randomized to either a propofol/remifentanil or an isoflurane/fentanyl group. In the propofol/remifentanil group, both drugs were used for induction and maintenance of anaesthesia; in the isoflurane/fentanyl group, anaesthesia was induced with etomidate and fentanyl and maintained with isoflurane and fentanyl. All patients received mivacurium for muscle relaxation and the lungs were ventilated mechanically. The use of propofol and remifentanil resulted in a faster emergence and an overall savings per case of [symbol: see text] 12.25 due to a reduction in personnel costs which outweighs the higher drug acquisition costs. RESULTS: In the propofol and remifentanil group, more patients were satisfied and would accept the same anaesthetic again. CONCLUSION: We conclude that propofol and remifentanil is more cost-effective than isoflurane/fentanyl due to its better recovery profile, reduced total direct costs and higher patient satisfaction.

Adjuvants, Anesthesia↗

Use of human preconditioned phagocytes for extracorporeal immune support: introduction of a concept.

Neutrophils are critical effector cells in humoral and innate immunity and play a vital role in phagocytosis and bacterial killing. If they and/or their specific functions are lacking, then immunoparalysis may occur, and severe diseases like systemic inflammatory response syndrome (SIRS) or sepsis can take a fatal course. In this paper, we discuss the possibility of using preconditioned cells in an extracorporeal biohybrid immune support system. A human promyelocytic cell line was stimulated for different times with all-trans retinoic acid. The resulting cells displayed major signs and functions of mature neutrophilic granulocytes including oxygen radical production, phagocytosis of living and dead Escherichia coli, Staphylococcus aureus, Candida albicans, intracellular killing, and interleukin production. The cells can be expanded to yield a sufficient cell mass, and subsequent prestimulation results in an expression of specific neutrophil functions. Extracorporeal bioreactor experiments seem to be feasible to test the benefit in immunoparalysis-associated diseases like SIRS or sepsis.

Bioreactors↗

Effects of histamine-1 receptor antagonism on leukocyte-independent plasma extravasation during endotoxemia.

PURPOSE: The purpose of this study was to investigate the role of histamine in mediating leukocyte-independent microvascular permeability and mast cell activation during endotoxemia. Microvascular permeability and mast cell activity were determined after inhibition of the L-selectin mediated leukocyte-adherence by fucoidin and after inhibition of histamine effects by the histamine H1-receptor antagonist diphenhydramine. MATERIALS AND METHODS: In male Wistar rats, leukocyte rolling, leukocyte adherence, microvascular permeability, and mast cell activity were determined in mesenteric postcapillary venules using intravital microscopy. After pretreatment with the histamine H1-receptor antagonist diphenhydramine, animals in the ETX/H1-ANT group received a continuous infusion of endotoxin. Animals in the ETX group underwent the same procedure, but received saline 0.9% instead of diphenhydramine. In both groups, leukocyte adherence was prevented by administration of fucoidin. Animals in the control group received volume-equivalent saline 0.9%. RESULTS: In the endotoxin-challenged groups, fucoidin prevented leukocyte rolling and reduced leukocyte adherence to values comparable to control group. In the ETX group and the ETX/H1-ANT group both microvascular permeability and mast cell activity increased significantly, starting at 60 minutes. Differences in mast cell activity between the ETX group and the ETX/H1-ANT group were significant at 60 minutes and at 120 minutes. Differences in microvascular permeability between the ETX/H1-ANT group and the ETX group were not significant. CONCLUSIONS: The leukocyte-independent microvascular damage during early endotoxemia cannot be inhibited efficiently by the H1-receptor antagonist diphenhydramine, indicating that histamine seems to play only a minor role in that pathophysiology. Furthermore, mast cells do not seem to be involved in the development of leukocyte-independent plasma extravasation during endotoxemia.

Animals↗

Methysergide attenuates leukocyte-independent plasma extravasation during endotoxemia.

PURPOSE: During endotoxemia, the early endothelial damage has been shown to be leukocyte independent. Therefore, it was the aim of our study to investigate the role of serotonin in mediating leukocyte-independent microvascular permeability during endotoxemia. Microvascular permeability was determined after inhibition of the L-selectin mediated leukocyte adherence by fucoidin and after inhibition of serotonin effects by the serotonin (5HT)-receptor antagonist methysergide. MATERIALS AND METHODS: In male Wistar rats, leukocyte rolling, leukocyte adherence, and macromolecular leakage were determined in mesenteric postcapillary venules using intravital microscopy. After pretreatment with the serotonin-receptor antagonist methysergide, animals in the FUCO/ETX/5HT-ANT group received a continuous infusion of endotoxin. Animals in the FUCO/ETX group underwent the same procedure but received saline 0.9% instead of methysergide. In both groups, leukocyte adherence was prevented by administration of fucoidin. Animals in the saline group received volume-equivalent saline 0.9%. RESULTS: In the endotoxin-challenged groups, fucoidin prevented leukocyte rolling and reduced leukocyte adherence to values comparable to saline group. In the FUCO/ETX group, macromolecular leakage increased significantly, starting at 60 minutes. Values in the saline group increased slightly, being significant at 120 minutes, whereas vascular permeability remained unchanged in the FUCO/ETX/5HT-ANT group. Differences in macromolecular leakage between the FUCO/ETX-group versus the FUCO/ETX/5HT-ANT group and the saline group were significant at 120 minutes. Differences in macromolecular leakage between the FUCO/ETX/5HT-ANT group and the saline group were not significant. CONCLUSIONS: The leukocyte-independent endothelial damage during early endotoxemia can be inhibited efficiently by the 5-HT-receptor antagonist methysergide, indicating that serotonin plays an important role in that pathophysiology.

Animals↗

Asymptomatic hypercalcemia due to an ectopic parathyroid adenoma in an 8-year-old boy.

The diagnosis of primary hyperparathyroidism in children is often delayed and is usually based on symptoms of hypercalcemia rather than abnormal laboratory values alone. We report the case of an 8-year-old boy with hypercalcemia, hypophosphatemia and mildly, but inadequately elevated intact parathyroid hormone (iPTH) who presented without any symptoms of hyperparathyroidism. Although imaging studies were misleading and four normal parathyroid glands were found intraoperatively, exploration of the thymus revealed an ectopic parathyroid adenoma. After removal of the ectopic gland, a rapid iPTH immunoassay proved immediate normalization of iPTH. This is the first report of sporadic isolated primary hyperparathyroidism diagnosed in an asymptomatic child on the basis of hypercalcemia and hypophosphatemia.

Adenoma↗

Clinical, biochemical and molecular genetic data in five children with Gitelman's syndrome.

Gitelman's variant of Bartter's syndrome, inherited hypokalemic alkalosis, is caused by mutation in the thiazide-sensitive NaCl co-transporter (NCCT). The main clinical symptoms are: muscular weakness, carpopedal spasm, constipation and short stature. The diagnosis was suspected in five children according to clinical criteria. All patients exhibited carpopedal spasm during febrile illness, three patients had short stature. Biochemical features were: metabolic alkalosis, hypokalemia, hypomagnesemia, low IGF-I levels, hyperkaliuria, hypernatriuria, hypocalciuria and normoprostaglandinuria. Three patients had elevated plasma renin activity and hyperaldosteronism. Mutational analysis of the NCCT gene confirmed the diagnosis in all five patients. Different forms of therapy, potassium and magnesium substitution, spironolactone and indomethacin failed to fully correct hypokalemia and hypomagnesemia, but markedly improved growth velocity and normalized IGF-I levels in the three patients with short stature. During therapy, clinical symptoms disappeared. We conclude that Gitelman's syndrome is a disorder with a variable symptom profile, but can be suspected on clinical signs already in early childhood. The early diagnosis is essential in preventing complications.

Adolescent↗

Transient pseudohypoaldosteronism secondary to posterior urethral valves--a case report and review of the literature.

In transient pseudohypoaldosteronism (TPHA), renal tubular resistance to aldosterone is thought to be secondary to renal disease. We report a case of TPHA caused by posterior urethral valves associated with urinary tract infection and review 62 cases previously reported. The infant presented with unspecific signs of vomiting and dehydration, so that pyloric stenosis was first suspected. Laboratory data and retroperitoneal sonography led to the diagnosis TPHA. This case illustrates that urine culture and renal ultrasonography should be performed in any infant with electrolyte disturbances to exclude infection or obstructive uropathy.

Aldosterone↗

Recurrent vomiting as first symptom of triple-a syndrome--a case report.

Triple-A syndrome is a very rare pathology in childhood, consisting of achalasia, alacrima and adrenal insufficiency. The order of manifestation of these three main symptoms is variable. Here we present a case of Triple-A syndrome with recurrent vomiting caused by achalasia as first symptom. At the same time, alacrima was diagnosed. Several years later adrenal insufficiency occurred and substitution therapy with hydrocortisone was started. The follow-up of patients with achalasia should pay attention to symptoms of adrenal insufficiency.

Adrenal Gland Diseases↗