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Biomedical subjects

B Schmidt

Publications and source records attributed to B Schmidt.

At least 109 records · Page 6Linked to original sources
PubMed2000

H2O/OH ratio determination in hydrous aluminosilicate glasses by static proton NMR and the effect of chemical shift anisotropy.

Static 1H NMR spectra of hydrous NaAlSi3O8 glasses have been acquired at low temperature (140 K) in order to quantitatively determine OH and H2O concentrations. Since both components overlap in the spectra, an unambiguous determination of the line shapes is required. The structurally bonded hydroxyl groups are well described by a Gaussian line and the water molecules exhibit a Pake doublet-like line shape due to the strong proton-proton dipolar interaction. However, at proton resonance frequencies used in this study (360 MHz), the Pake doublet has an asymmetric line shape due to chemical shift anisotropy (CSA), which is significant and must be included in any simulation in order to reproduce the experimental line shape successfully. The simulations for rigid water molecules dissolved in our hydrous aluminosilicate glasses result in a CSA of 30+/-5 ppm and a dipolar interaction constant of 63.8+/-2.5 kHz (i.e., dipolar coupling constant (DCC) of 42.6+/-1.7 kHz), corresponding to a proton-proton distance of r(ij) = 154+/-2 pm. In contrast to earlier work, water speciation obtained from the simulations of our 1H NMR spectra are in excellent agreement with those obtained from infrared (IR) spectroscopy.

Aluminum Silicates↗
PubMed2000

Value of bronchial artery embolisation with platinum coils in tumorous pulmonary bleeding.

We performed bronchial artery embolizations (BAE) using platinum coils with Dacron fibres in 30 consecutive patients with haemoptysis due to bronchial carcinoma. The aim of the study was to compare immediate results of bleeding cessation, recurrence and survival rates with a historical control group of 15 patients with tumorous pulmonary bleeding who were treated conservatively (non-BAE-group). Bronchial artery embolisation with platinum coils stopped active bleeding in all patients immediately. Comparing the BAE group and controls the cessation of first time haemoptysis (BAE 100% versus non-BAE 93%) and the rates of bleeding recurrence (BAE 50% versus non-BAE 47%) were similar in either group. In case of recurrent bleeding, repeated BAE led to a definite cessation of pulmonary haemorrhage in every case. In contrast, all patients with recurrent haemoptysis without a repeated BAE (8 patients, 27%) and all patients with bleeding recurrence in the non-BAE group died from pulmonary haemorrhage (8 patients, 53%). The mean survival time of the BAE group was significantly longer compared with the non-BAE group, 139 (range: 1-818) days versus 62 (range: 1-186) days (P<0.05). We conclude that consistent BAE proved beneficial in tumorous pulmonary bleeding, particularly with regard to the permanent arrest of haemorrhage in case of recurrence.

Aged↗
PubMed2000

DALI apheresis in hyperlipidemic patients: biocompatibility, efficacy, and selectivity of direct adsorption of lipoproteins from whole blood.

Recently, the first apheresis technique for direct adsorption of low-density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] from whole blood (DALI) was developed that does not require a prior plasma separation. That markedly simplifies the extracorporeal circuit. The aim of the present study was to test the acute biocompatibility, efficacy, and selectivity of DALI apheresis. In a prospective clinical study, 6 hypercholesterolemic patients suffering from angiographically proven atherosclerosis were treated 4 times each by DALI. 1.3 patient blood volumes were treated per session at blood flow rates of 60-80 ml/min using 750 or 1,000 ml of polyacrylate/polyacrylamide adsorber gel. The anticoagulation consisted of an initial heparin bolus followed by a citrate infusion. The sessions were clinically essentially uneventful. Mean corrected reductions of lipoproteins amounted to 65% for LDL-cholesterol, 54% for Lp(a), 28% for triglycerides, 1% for HDL-cholesterol, and 8% for fibrinogen. The selectivity of lipoprotein removal was high. Cell counts remained virtually unchanged and no signs of hemolysis or clotting were detected. Cell activation parameters elastase, beta-thromboglobulin, interleukin-1beta, and IL-6 showed no significant increase. Complement activation was negligible. There was significant, but clinically asymptomatic, bradykinin activation in the adsorber with mean maxima of 12,000 pg/ml in the efferent line at 1,000 ml of treated blood volume. In conclusion, DALI proved to be safe, selective, and efficient for the adsorption of LDL-C and Lp(a), which simplifies substantially the extracorporeal therapy in hypercholesterolemic patients.

Acrylic Resins↗
PubMed2000

[Psychotherapeutic and psychosocial therapy in general practice. Results of demonstration project on quality management in psychosocial primary care].

Since 1987, psychosocial primary care (PPC) provided by General Practitioners, are reimbursed by German health insurances. The aim of the psychosocial primary care is to improve recognition and treatment of mental disorders in the primary care sector. As a part of a eight-center national demonstration program on quality management in the outpatient services, General Practitioners (n = 191) from 5 regions participated in the study. 1341 treatment episodes of patients with predominately psychosocial strain were documented. Differences between psychosocial strain, treatment and outcome were determined by analyses of variance. Men and patients beyond the age of 65 were underrepresented. Psychosocial treatments were offered more often to those patients, who had the highest level of anxiety and depression. Patients with physical illness, with pain and without psychological attribution to the illness belief were offered less psychosocial interventions and reached a worse outcome. The study outcome helps to improve training programs as to recognition and treatment of psychosocial problems in primary care. Male and generally elderly patients with somatic symptoms and lack of psychological attribution need a special psychosocial intervention to improve the outcome.

Adult↗
PubMed2000

[A 42-year-old patient with the hemolytic-uremic syndrome under gemcitabine therapy for an adenocarcinoma of the liver. The hemolytic-uremic syndrome and gemcitabine].

We report on the case of a 42-year-old man suffering from an irresectable adenocarcinoma of the liver. The patient was treated with 5-fluorouracil for 6 months when the disease progressed and second line therapy with gemcitabine was started. After 4 months diastolic blood pressure increased and edema of the legs as well as vomiting occurred. Laboratory tests revealed anemia and thrombopenia accompanied by an elevation of plasma D-dimer, lactatdehydrogenase, creatinine, and urea levels in the serum. In addition, a pronounced proteinuria as well as renal hematuria were detected and subsequently a hemolytic uremic syndrome was diagnosed. After treatment with high-dose glucocorticoids, anticoagulants and transfusions of packed RBC the course of disease improved. Since Gemcitabine is now widely used for treatment of solid organ cancer (e.g. pancreatic adenocarcinoma, biliary tract cancer, lung cancer etc.), it is necessary to be aware of Gemcitabine-induced hemolytic uremic syndrome as a rare but potentially fatal side effect.

Acute Kidney Injury↗
PubMed2000

Lobular distribution pattern of lactate dehydrogenase and 6-phosphogluconate dehydrogenase activity in rat liver.

Lactate dehydrogenase (LDH) and 6-phosphogluconate dehydrogenase (6-PGDH) activities were measured in lobular areas expanding between 3 portal tracts and an efferent central vein in the livers of male Wistar rats, using a Lowry technique. The maximum of LDH activity was found in a nearly uniform broad area in the lobular periphery. From that area values decreased along periportal/septal-->perivenous gradients, but only slightly within that area along the periportal-->septal axis of the vascular septum. Maximum values of 6-PGDH activity were present in an intermediate area close to the central vein demonstrating a rather inhomogeneous distribution pattern without a clear definition of zonal limits. Our data on the distribution pattern of LDH are in agreement with the concept of the metabolic lobulus and are supported by a recent evaluation of the vascular architecture in rat liver. The lobular distribution pattern of 6-PGDH cannot be interpreted without doubt in accordance with that concept.

Animals↗
PubMed2000

Low level of cross-resistance to amprenavir (141W94) in samples from patients pretreated with other protease inhibitors.

The therapeutic success of an antiretroviral salvage regimen containing protease inhibitors (PI) is limited by PI-resistant viral strains exhibiting various degrees of resistance and cross-resistance. To evaluate the extent of cross-resistance to the new PI amprenavir, 155 samples from 132 human immunodeficiency virus type 1-infected patients were analyzed for viral genotype by direct sequencing of the protease gene. Concomitantly, drug sensitivity to indinavir, saquinavir, ritonavir, nelfinavir, and amprenavir was analyzed by a recombinant virus assay. A total of 111 patients had been pretreated with 1-4 PI, but all were naive to amprenavir. A total of 105 samples (67.7%) were sensitive to amprenavir; 25 samples (16.1%) were intermediately resistant, and another 25 samples were highly resistant (4- to 8-fold- and >8-fold-reduced sensitivity, respectively). The mutations 46I/L, 54L/V, 84V, and 90M showed the strongest association with amprenavir resistance (P < 0. 0001). The scoring system using 84V and/or any two of a number of mutations (10I/R/V/F, 46I/L, 54L/V, and 90M) predicted amprenavir resistance with a sensitivity of 86.0% and a specificity of 81.0% within the analyzed group of samples. Of 62 samples with resistance against 4 PI, 23 (37.1%) were still sensitive to amprenavir. In comparison, only 2 of 23 samples (8.7%) from nelfinavir-naive patients with resistance against indinavir, saquinavir, and ritonavir were still sensitive to nelfinavir. Amprenavir thus appears to be an interesting alternative for PI salvage therapy.

Carbamates↗
PubMed2000

Chronic parvovirus B-19 meningoencephalitis with additional detection of Epstein-Barr virus DNA in the cerebrospinal fluid of an immunocompetent patient.

Parvovirus B19 DNA was detected by polymerase chain reaction in the brain biopsy specimen from a 67-year-old immunocompetent woman with severe chronic lymphocytic meningoencephalitis. In addition to parvovirus B19, Epstein-Barr virus DNA was identified in the CSF. Genomic material from Epstein-Barr virus was absent in the brain tissue. Clinical symptoms and CSF pleocytosis improved under long-term corticosteroid-treatment. The aetio-pathogenetic role of parvovirus B19 and the possible meaning of the additionally detected Epstein-Barr virus DNA are discussed.

Aged↗
PubMed2000

Evaluation of a method for noninvasive intracranial pressure assessment during infusion studies in patients with hydrocephalus.

OBJECT: A mathematical model previously introduced by the authors allowed noninvasive intracranial pressure (nICP) assessment. In the present study the authors investigated this model as an aid in predicting the time course of raised ICP during infusion tests in patients with hydrocephalus and its suitability for estimating the resistance to outflow of cerebrospinal fluid (Rcsf). METHODS: Twenty-one patients with hydrocephalus were studied. The nICP was calculated from the arterial blood pressure (ABP) waveform by using a linear signal transformation, which was dynamically modified by the relationship between ABP and cerebral blood flow velocity. This model was verified by comparison of nICP with "real" ICP measured during lumbar infusion tests. In all simulations, parallel increases in real ICP and nICP were evident. The simulated Rcsf was computed using nICP and then compared with Rcsf computed from real ICP. The mean absolute error between real and simulated Rcsf was 4.1 +/- 2.2 mm Hg minute/ml. By the construction of simulations specific to different subtypes of hydrocephalus arising from various causes, the mean error decreased to 2.7 +/- 1.7 mm Hg minute/ml, whereas the correlation between real and simulated Rcsf increased from R = 0.73 to R = 0.89 (p < 0.001). CONCLUSIONS: The validity of the mathematical model was confirmed in this study. The creation of type-specific simulations resulted in substantial improvements in the accuracy of ICP assessment. Improvement strategies could be important because of a potential clinical benefit from this method.

Adult↗
PubMed2000

[Primary psychosomatic management in general practice. Results of a German nationwide demonstration project of quality assurance].

In the frame of a national demonstration program, psychosocial care of patients with psychological and psychosomatic problems were assessed. General practitioners (n = 191) from six regions participated in the study. 1341 treatment episodes of patients with predominately psychosocial symptoms were documented. Anxiety (62%), depression (51%) and marital/family conflicts (44%) were the most frequent symptoms. Somatic treatment and psychosocial intervention were offered equally. Patients with psychosocial treatment achieved better results. Partners and family members were rarely integrated into therapy. The procedures employed to improve outcome were quality circles, family-orientated case conferences, consultation services and collaborative groups.

Combined Modality Therapy↗
PubMed2000

Phenotypic HIV-1 resistance correlates with treatment outcome of nelfinavir salvage therapy.

In order to analyse whether drug sensitivity testing would be beneficial for clinical decision-making in heavily pretreated patients, we retrospectively studied viral genotype and phenotypic drug resistance in 12 HIV-1-infected patients, each of them with a history of failing at least one therapeutic regimen including one or two protease inhibitors (PIs). The salvage therapy included nelfinavir as new PI in all cases. Four patients showed a sustained and five patients a transient viral load decrease. Three patients failed to show a significant decline of plasma HIV-1 RNA. In the baseline samples of these cases, resistance against all components of their combination therapy could be detected, whereas at least one antiretroviral drug was still active in the cases with transient treatment response. All patients with sustained therapy response harboured viruses that were either fully sensitive or resistant to only one of the drugs administered. In our study, phenotypic drug resistance was predictive for the success of antiretroviral salvage regimens.

Amino Acid Sequence↗
PubMed1999

Polycations as displacer in high-performance bioseparation.

Displacement chromatography is an interesting but up to now rarely used type of preparative biochromatography. The lack of well-engineered and accessible displacer contributes to this phenomenon. In this paper a novel type of displacer is introduced for cation-exchange displacement chromatography, which will soon become commercially available. The molecule is a well-defined PolyDADMAC [poly(diallyldimethylammonium chloride)] with a molar mass of less than 35000 g/mol, an exclusively linear structure and a molar mass polydispersity of less than 1.5. A method for synthesizing such a polymer at high yields is described. The PolyDADMAC is shown to be an efficient displacer of basic proteins from strong cation-exchange columns.

Chromatography, Ion Exchange↗
PubMed1999

The iron sulfur protein AtsB is required for posttranslational formation of formylglycine in the Klebsiella sulfatase.

The catalytic residue of eukaryotic and prokaryotic sulfatases is a alpha-formylglycine. In the sulfatase of Klebsiella pneumoniae the formylglycine is generated by posttranslational oxidation of serine 72. We cloned the atsBA operon of K. pneumoniae and found that the sulfatase was expressed in inactive form in Escherichia coli transformed with the structural gene (atsA). Coexpression of the atsB gene, however, led to production of high sulfatase activity, indicating that the atsB gene product plays a posttranslational role that is essential for the sulfatase to gain its catalytic activity. This was verified after purification of the sulfatase from the periplasm of the cells. Peptide analysis of the protein expressed in the presence of AtsB revealed that half of the polypeptides carried the formylglycine at position 72, while the remaining polypeptides carried the encoded serine. The inactive sulfatase expressed in the absence of AtsB carried exclusively serine 72, demonstrating that the atsB gene is required for formylglycine modification. This gene encodes a 395-amino acid residue iron sulfur protein that has a cytosolic localization and is supposed to directly or indirectly catalyze the oxidation of the serine to formylglycine.

Alanine↗
PubMed1999

Amino acid residues forming the active site of arylsulfatase A. Role in catalytic activity and substrate binding.

Arylsulfatase A belongs to the sulfatase family whose members carry a Calpha-formylglycine that is post-translationally generated by oxidation of a conserved cysteine or serine residue. The formylglycine acts as an aldehyde hydrate with two geminal hydroxyls being involved in catalysis of sulfate ester cleavage. In arylsulfatase A and N-acetylgalactosamine 4-sulfatase this formylglycine was found to form the active site together with a divalent cation and a number of polar residues, tightly interconnected by a net of hydrogen bonds. Most of these putative active site residues are highly conserved among the eukaryotic and prokaryotic members of the sulfatase family. To analyze their function in binding and cleaving sulfate esters, we substituted a total of nine putative active site residues of human ASA by alanine (Asp29, Asp30, Asp281, Asn282, His125, His229, Lys123, Lys302, and Ser150). In addition the Mg2+-complexing residues (Asp29, Asp30, Asp281, and Asn282) were substituted conservatively by either asparagine or aspartate. In all mutants Vmax was decreased to 1-26% of wild type activity. The Km was more than 10-fold increased in K123A and K302A and up to 5-fold in the other mutants. In all mutants the pH optimum was increased from 4.5 by 0.2-0.8 units. These results indicate that each of the nine residues examined is critical for catalytic activity, Lys123 and Lys302 by binding the substrate and the others by direct (His125 and Asp281) or indirect participation in catalysis. The shift in the pH optimum is explained by two deprotonation steps that have been proposed for sulfate ester cleavage.

Amino Acid Sequence↗
PubMed1999

Over-expression and amplification of the c-myc gene in human urothelial carcinoma.

To understand the mechanisms underlying increased expression of Myc protein in human urinary bladder cancer, expression of c-myc mRNA and the copy number of the c-myc gene were determined. Expression of mRNA was measured by quantitative RT-PCR in 40 urothelial carcinomas and in 18 histologically normal mucosae. Mean expression in tumors was significantly increased (3.23+/-2.63 AU vs. 1.90+/-0.95 AU, p < 0.023) and exceeded the highest level in normal mucosa in 15 (37.5%) tumors. The c-myc gene copy number was higher than in leukocytes and normal bladder mucosa in 14 of 40 tumors, but only 3 among these showed a more than 4-fold increase indicative of gene amplification. Most, but not all, tumors with elevated expression displayed an increased gene copy number (p < 0.0001). In line with other studies of the protein level, no significant association either of c-myc mRNA over-expression or of increased gene copy number with tumor stage or grade was observed. The data indicate that elevated mRNA expression as a consequence of increases in c-myc gene copy number often underlies Myc protein over-expression in bladder cancer. This increase may be a consequence of, most frequently, chromosome 8q gain and, occasionally, gene amplification, while in some tumors deregulation of mRNA expression occurs without evident changes in the c-myc gene copy number.

Aged↗
PubMed1999

Sequence determinants directing conversion of cysteine to formylglycine in eukaryotic sulfatases.

Sulfatases carry at their catalytic site a unique post-translational modification, an alpha-formylglycine residue that is essential for enzyme activity. Formylglycine is generated by oxidation of a conserved cysteine or, in some prokaryotic sulfatases, serine residue. In eukaryotes, this oxidation occurs in the endoplasmic reticulum during or shortly after import of the nascent sulfatase polypeptide. The modification of arylsulfatase A was studied in vitro and was found to be directed by a short linear sequence, CTPSR, starting with the cysteine to be modified. Mutational analyses showed that the cysteine, proline and arginine are the key residues within this motif, whereas formylglycine formation tolerated the individual, but not the simultaneous substitution of the threonine or serine. The CTPSR motif was transferred to a heterologous protein leading to low-efficient formylglycine formation. The efficiency reached control values when seven additional residues (AALLTGR) directly following the CTPSR motif in arylsulfatase A were present. Mutating up to four residues simultaneously within this heptamer sequence inhibited the modification only moderately. AALLTGR may, therefore, have an auxiliary function in presenting the core motif to the modifying enzyme. Within the two motifs, the key residues are fully, and other residues are highly conserved among all known members of the sulfatase family.

Alanine↗
PubMed1999

Pinta in Austria (or Cuba?): import of an extinct disease?

BACKGROUND: Pinta, 1 of the 3 nonvenereal treponematoses, is supposed to be extinct in most areas in South and Central America, where it was once endemic. Only scattered foci may still remain in remote areas in the Brazilian rain forest, and the last case from Cuba was reported in 1975. OBSERVATION: A native Austrian woman, who had lived for 7 years in Cuba and was married to a Cuban native, developed a singular psoriasiform plaque on her trunk and several brownish papulosquamous lesions on her palms and soles during a visit to her home in Austria. Positive serological findings for active syphilis and the detection of spirochetes in the trunk lesion indicated early secondary syphilis, but an extensive case history and the clinical appearance fulfilled all criteria for pinta. CONCLUSION: The acquisition of a distinct clinical entity, pinta, in a country where it was formerly endemic but now is believed to be extinct raises the question of whether the disease is in fact extinct or whether syphilis and pinta are so similar that no definite distinction is possible in certain cases.

Adult↗