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Biomedical subjects

H Fischer

Publications and source records attributed to H Fischer.

At least 235 records · Page 13Linked to original sources
PubMed1994

Colonic and anorectal dysfunction in a patient with the tethered cord syndrome.

Although visceral dysfunction is commonly encountered in the tethered cord syndrome, alteration of intestinal motor and sensory function has not yet been specifically addressed in this neurological disorder. We report the case of a 54-yr-old woman with a rare form of adult onset tethered cord syndrome who presented to us for preoperative assessment of marked constipation, urinary and fecal incontinence, and a rectal prolapse. It is shown that the tethered cord syndrome causes complex clinical patterns of bowel dysfunction and that careful efforts are mandatory to differentiate their underlying pathology. Specific diagnostic procedures directed to intestinal motility and perception were of decisive importance in enabling us to apply the appropriate treatment to our patient.

Colon↗
PubMed1993

Low serum alpha-fetoprotein level in patients with hepatocellular carcinoma as a predictor of response to 5-FU and interferon-alpha-2b.

BACKGROUND: A Phase II clinical trial was conducted to evaluate the efficacy of intravenous fluorouracil (5-FU) and subcutaneous recombinant interferon-alpha-2b (rIFN-alpha-2b) in the treatment of hepatocellular carcinoma (HCC) and to define factors that might be predictive of a response to treatment. METHODS: Twenty-nine patients were registered on the protocol. 5-FU was administered as a continuous intravenous (i.v.) infusion (dose = 750 mg/m2) for 5 consecutive days. rIFN-alpha-2b was administered subcutaneously (SC) (dose = 5 x 10(6) um/m2) once a day on days 1, 3, and 5 of the 5-FU infusion. The treatment was repeated at 14-day intervals. Responses were assessed at the end of one course of therapy, which was equivalent to four treatments. RESULTS: Of the 28 patients evaluable for response, 5 (18%) had a partial response, and 1 (4%) had a minor response. Responses lasted from more than 2 to more than 24 months (median, 11.5 months). Ten (36%) patients experienced no response, and 12 (43%) had progressive disease. The 6 responders were part of a group of 16 patients who had pretreatment levels of serum alpha-fetoprotein (AFP) of 50 ng/ml or less and a group of 8 whose tumors involved 50% or less of the liver parenchyma. Mucositis, which occurred in 54% of the patients, was the most common toxicity associated with the treatment regimen. Diarrhea and dermatitis were observed in 16% and 17% of the patients, respectively; fatigue, thrombocytopenia, granulocytopenia, neurologic toxicity, and nausea and vomiting were not commonly seen. CONCLUSIONS: The regimen of i.v. 5-FU and SC rIFN-alpha-2b was well tolerated and induced durable partial response in 31% (5 of 16) of patients with HCC who had low levels of serum AFP and in those with 50% or less of liver replacement. In contrast, the treatment regimen was ineffective in patients with HCC who had high levels of serum AFP or extensive liver disease.

Adolescent↗
PubMed1993

ATP hydrolysis is not stoichiometrically linked with proteolysis in the ATP-dependent protease La from Escherichia coli.

Protein degradation in Escherichia coli involves the ATP-dependent serine protease La. Protease La is a homotetramer with one proteolytic and one ATP binding site per monomer. Its proteolytic activity has been shown to be highly increased by simultaneous hydrolysis of ATP, which is essential for the degradation of protein substrates by this enzyme. We have cloned and purified a proteolytically inactive La mutant, in which the catalytically active serine residue at position 679 was replaced by alanine. Fluorescence and circular dichroism spectra of the purified wild type and mutant enzyme revealed identical conformations of the proteins. Based on this observation, the catalytic properties of the wild type enzyme and the S679A mutant were compared. Although the S679A mutant lacks proteolytic activity toward both peptide and protein substrates under all conditions investigated, its ATPase activity is completely unaffected by the removal of the protease activity. Since protein substrates stimulate the ATP-dependent hydrolysis of peptides by protease La, it has been argued that this stimulation is due to interactions with a regulatory binding site on the enzyme. In accordance with this model, protein substrates such as alpha-casein and denatured bovine serum albumin stimulate the ATPase activity of the S679A mutant to the same degree as in the active protease. Therefore, the intrinsic ATPase activity of protease La as well as its stimulation is not dependent on the simultaneous hydrolysis of the protein substrate.

ATP-Dependent Proteases↗
PubMed1993

Quinidine-sensitive K+ channels in the basolateral membrane of embryonic coprodeum epithelium: regulation by aldosterone and thyroxine.

Basolateral K+ channels and their regulation during aldosterone- and thyroxine-stimulated Na+ transport were studied in the lower intestinal epithelium (coprodeum) of embryonic chicken in vitro. Isolated tissues of the coprodeum were mounted in Ussing chambers and investigated under voltage-clamped conditions. Simultaneous stimulation with aldosterone (1 mumol.l-1) and thyroxine (1 mumol.l-1) raised short-circuit current after a 1- to 2-h latent period. Maximal values were reached after 6-7 h of hormonal treatment, at which time transepithelial Na+ absorption was more than tripled (77 +/- 11 microA.cm-2) compared to control (24 +/- 8 microA.cm-2). K+ currents across the basolateral membrane were investigated after permeabilizing the apical membrane with the pore-forming antibiotic amphotericin B and application of a mucosal-to-serosal K+ gradient. This K+ current could be dose dependently depressed by the K+ channel blocker quinidine. Fluctuation analysis of the short-circuit current revealed a spontaneous and a blocker-induced Lorentzian noise component in the power density spectra. The Lorentzian corner frequencies increased linearly with the applied blocker concentration. This enabled the calculation of single K+ channel current and K+ channel density. Single K+ channel current was not affected by stimulation, whereas the number of quinidine-sensitive K+ channels in the basolateral membrane increased from 11 to 26.10(6).cm-2 in parallel to the hormonal stimulation transepithelial Na+ transport. This suggests that the basolateral membrane is a physiological target during synergistic aldosterone and thyroxine regulation of transepithelial Na+ transport for maintaining intracellular K+ homeostasis.

Aldosterone↗
PubMed1993

[The selective arterial and venous MR angiography of intracranial arteriovenous malformations].

This study evaluates the usefulness of MR angiography (MRA) in analysing cerebral arterial blood supply and venous drainage in patients with intracranial arteriovenous malformations (AVM). Selective MRA of the carotid, middle cerebral or vertebrobasilar territories was performed by means of presaturation of up to three of the brain-supplying arteries at the level of the middle or lower neck (angled presaturation slabs). Results obtained with selective, non-selective arterial, as well as venous MRA in 13 consecutive patients were compared with the findings at intraarterial angiography, the latter serving as the "gold standard". Sensitivity in identifying major feeding arteries was 100%. Determination of the absolute and relative AVM sizes at selective MRA corresponded with IAA. The mean difference was 17.6 and 3.9% respectively. Both display of superficial and deep venous drainage was provided by 2-dimensional venous MRA. The authors conclude that selective MRA of cerebral arteries as used here is a powerful non-invasive method to demonstrate blood supply by single feeding vessels in intracranial malformations. 2D venous MRA permits an accurate evaluation of the venous drainage pattern.

Adult↗
PubMed1993

[Quantification of extracranial carotid stenosis. Magnetic resonance angiography and Doppler sonography versus intra-arterial angiography].

UNLABELLED: To assess various non-invasive techniques for quantifying internal carotid artery CA stenosis, per cent luminal diameter reduction on intraarterial angiograms (IAA) was measured in 63 patients with ICA stenosis or occlusion. These data were compared with independent measurements based on MR-angiography, continuous-wave (cw) Doppler ultrasonography, systolic peak flow velocity and colour Doppler assisted duplex imaging. Correlations with IAA were equally strong for MR angiography, cw Doppler and colour Doppler analysis (0.95; 0.92; 0.92). Positive predictive values for > or = 70% ICA stenosis were lower and negative predictive values were higher for cw Doppler (0.85; 0.92) and colour duplex analysis (0.81; 0.94) than for MR angiography (0.86; 0.88). Statistical analysis showed non-linear correlations between percentage of lumen diameter narrowing and the length of the zone of signal intensity loss (0.72) and maximum systolic peak flow velocity (0.77). CONCLUSION: Several non-invasive methods do compare with IAA in identifying and quantifying high-grade ICA stenosis and may suffice for decisions on treatment.

Adult↗
PubMed1993

[The hemodynamics and anatomy of the circle of Willis. The technic and clinical value of selective MR angiography].

This study evaluates the usefulness of MR angiography in analysing the individual collateral flow dynamics and anatomy of the circle of Willis in 56 patients with high-grade extracranial carotid stenosis or occlusion. Selective MRA of the carotid or vertebrobasilar area was performed by means of presaturation up to the brain-supplying arteries at the level of the middle neck (angled presaturation slabs). Results obtained with selective and non-selective MRA in 56 consecutive patients were compared with the findings at transcranial Doppler ultrasonography and arterial angiography. Ischaemic cerebral infarctions were classified by computerized tomography and correlated with the results of collateral flow analysis: Sensitivity of selective MRA in detecting intracranial collateral flow via anterior or posterior communicating artery was 96 and 97%, respectively; sensitivity in depicting extracranial transorbital flow was lower (71%). Non-selective MRA was 100% sensitive in detecting a non-filling of the horizontal (A1) segment of the anterior cerebral artery and in identifying an origin of the posterior cerebral artery from the intracranial carotid artery. Slow flow infarctions occurred more frequently in patients with transorbital and posterior-to-anterior collateral flow than in patients with collateral flow via anterior communicating artery.

Angiography↗
PubMed1993

Early changes of body composition in human immunodeficiency virus-infected patients: tetrapolar body impedance analysis indicates significant malnutrition.

Total body water, body fat, body cell mass (BCM), extracellular mass (ECM), and the ECM-BCM ratio by impedance analysis were determined in 193 human immunodeficiency virus (HIV)-infected patients and 340 control subjects. Walter Reed (WR) classification was WR 2 in 26, WR 3-5 in 85, and WR 6 in 82 patients. Whereas resistance was increased, reactance and the phase angle were significantly reduced in all patient groups. Neither body weight nor body mass index (BMI) was affected in WR 2 patients, but BCM was reduced (31.9 +/- 4.3 vs 35.8 +/- 7.3 kg, P < 0.007) and ECM (31.2 +/- 4.4 vs 28.8 +/- 3.8 kg) as well as ECM-BCM ratio increased (0.99 +/- 0.14 vs 0.83 +/- 0.16, P < 0.001). In contrast to WR classification, diarrhea did not correspond with malnutrition. A loss of BCM (malnutrition) occurred already in otherwise symptomless HIV-infected patients (WR 2). This effect can be measured by tetrapolar impedence analysis but not by body weight or BMI.

Adult↗
PubMed1993

Identification of a supernumerary der(18) chromosome by a rational strategy for the cytogenetic typing of small marker chromosomes with chromosome-specific DNA probes.

A case of a supernumerary der(18) marker chromosome is presented. The chromosomal origin of the marker chromosome was not evident by traditional chromosome analysis, but was determined by PRimed IN Situ labelling (PRINS) with chromosome specific centromere probes as primers for chain elongation in situ. For this purpose a strategy was developed which, in a few simple reactions, makes it possible unequivocally to determine the origin of any small marker chromosome. The approach does not require any hints about the origin of the chromosome prior to the analysis, since the chromosomal origin of the marker is established through PRINS reactions with pooled and single chromosome-specific centromere probes. Identification, mosaic screening and structural analysis require a total of 8-9 such reactions and may, due to the extreme speed of the PRINS reaction, be obtained within a single working day.

Chromosome Aberrations↗
PubMed1993

Between-method correlation in quantifying internal carotid stenosis.

BACKGROUND AND PURPOSE: The degree of internal carotid stenosis has emerged as the most important predictor of ischemic stroke in extracranial carotid artery disease. The purpose of this study was to assess the validity of the noninvasive techniques for quantifying internal carotid stenosis with respect to the accepted standard of intra-arterial angiography. METHODS: We measured the maximum percentage reduction in luminal diameter on the intra-arterial digital subtraction angiograms of 56 symptomatic patients with extracranial internal carotid stenosis (n = 77) or occlusion (n = 20). These data were compared with independent measurements based on continuous-wave Doppler ultrasonography, pulsed-wave Doppler spectrum analysis, color Doppler-assisted duplex imaging, and magnetic resonance angiography. RESULTS: Correlations with intra-arterial angiography were equally strong (r > .90) for magnetic resonance angiography, continuous-wave Doppler, and color duplex analysis. Positive and negative predictive values for (therapeutically relevant) 70% to 99% stenosis were higher for continuous-wave Doppler (.82, .97) and color duplex (.84, .98) than for magnetic resonance angiography (.79, .81). Also, accuracy in quantifying high-grade stenosis was better for both of these ultrasonographic techniques, mainly due to the frequent occurrence of a "flow gap" on the magnetic resonance angiograms. Continuous-wave Doppler and magnetic resonance angiography, but not color duplex, failed to detect slow residual arterial flow in one and two cases of symptomatic "pseudo-occlusion" of the internal carotid, respectively. CONCLUSIONS: (1) Several noninvasive methods compare well with intra-arterial angiography in identifying and quantifying high-grade internal carotid stenosis; (2) the use of these noninvasive methods may suffice for treatment decisions; and (3) because residual between-method disagreement is partly explained by principles of physics, the validity of continuous-wave Doppler and color duplex in quantifying 60% to 99% stenosis is likely to be underestimated by correlation with intra-arterial angiography.

Blood Flow Velocity↗
PubMed1993

[Age and brain weight].

The paper presents data on the growth of the brain weight of 745 boys and 558 girls from birth to the 54th week of life and also data on the age differentiation of the brain weight of 688 male and 404 female persons in the age groups from the 6th to the 90th year of life.

Adolescent↗
PubMed1993

[The psychosocial status of HIV-positive mothers and their children].

We studied the psycho-social circumstances of HIV-positive women and their children, who were born between January 1, 1984 and June 30, 1991 and are being treated at the Department of Pediatrics. We interviewed 19 women out of 21 families using the problem-centered interview technique according to Witzel. 29 out of 30 children were older than 18 months. Four children were HIV-positive and the serology of one patient aged 12 months who had been perinatally exposed was yet unclarified. The study showed massive problems within these families, such as considerable partner problems, drug abuse and social isolation. Furthermore, there was a lack of child care to relieve the mothers. The predominance of drug problems and insufficient experience of social institutions with the problematic nature of HIV-infection in mothers and children require more efficient preventive measures.

Child↗
PubMed1993

[Physical activity, nutritional counseling and psychological guidance in treatment of obese children. A controlled follow-up study over six months].

BACKGROUND: Only multi-faceted treatment programs may influence childhood obesity. METHODS: Thus our program consists of physical exercise, dietary counseling (but no caloric reduction) and psychological support. 17 obese children, aged 7 to 12 years, participated in this combined out-patient therapy program. The children were compared to a control group of 17 obese children who only received an initial dietary instruction. RESULTS: After 6 months program children showed a very significant decrease of percentage overweight (-11.5%), whereas control children showed an increase of +2.8%. In contrast to control children program children improved their physical performance rather significantly. Both groups improved in body-esteem, whereas only program children showed a better self-esteem. Positive trends in lipid metabolism did not reach level of significance. CONCLUSIONS: We conclude that a combined program of exercise and diet improves short-term results in the treatment of childhood obesity, even without insisting on caloric reduction.

Behavior Therapy↗
PubMed1992

Stimulation of human naive and memory T helper cells with bacterial superantigen. Naive CD4+45RA+ T cells require a costimulatory signal mediated through the LFA-1/ICAM-1 pathway.

The role of the accessory molecule ICAM-1 in activation of subpopulations of human T cells was examined using the bacterial superantigen staphylococcal enterotoxin A (SEA) as a MHC class II and TCR-dependent polyclonal T cell activator. Human T cells responded with different sensitivity to SEA when presented on mouse accessory cells expressing a human transfected MHC class II gene product. Mouse L cells cotransfected with both MHC class II (DR2A or DR7) and ICAM-1-stimulated T cells at 100-fold lower concentrations of SEA as compared to the single transfected cells. mAb reacting with the CD11a, CD18, or ICAM-1 molecules efficiently inhibited T cell activation with the cotransfected HLA-DR2A/ICAM-1 cell but did not influence T cell activation with the HLA-DR2A single transfected cell. Analysis of the ICAM-1 requirement on CD4+ memory (CD4+45RO+) and naive (CD4+45RA+) T cells revealed that CD4+45RA+ naive Th cells were hyporesponsive to SEA-induced activation with the HLA-DR2A single transfectant. However, cotransfection of ICAM-1 enabled these cells to respond to low doses of SEA implicating that they are more dependent on accessory molecules than the CD4+45RO+ cells. rICAM-1 immobilized on a plastic surface, was able to strongly costimulate SEA-induced T cell activation with the HLA-DR2A single transfectant, suggesting that costimulatory signals mediated to the T cells through LFA-1 can be delivered physically separated from the TCR signal. CD4+45RO+ memory and CD4+45RA+ naive Th cells apparently differ in their capacities to be activated by SEA bound to HLA-DR. Although the TCR molecule densities are similar in these two subsets, costimulation with ICAM-1 is required for activation of the CD4+45RA+, but not the CD4+45RO+ T cell subset at 1 to 10,000 ng/ml concentrations of SEA. This observation indicates different activation thresholds of naive and memory Th cells when triggering the TCR over a wide dose interval of superantigen.

Antigens, Bacterial↗
PubMed1992

Carbachol-activated calcium entry into HT-29 cells is regulated by both membrane potential and cell volume.

Intracellular Ca2+ ([Ca2+]i) was measured in single Cl(-)-secretory HT-29/B6 colonic carcinoma cells with the Ca2+ probe fura-2 and digital imaging microscopy. Resting [Ca2+]i was 63 +/- 3 nM (n = 62). During treatment with the muscarinic agonist carbachol, [Ca2+]i rapidly increased to 901 +/- 119 nM and subsequently reached a stable level of 309 +/- 23 nM, which depended on Ca2+ entry into the cells from the extracellular solution. The goal of this study was to characterize the Ca2+ entry pathway across the cell membrane with respect to its dependence on membrane potential and cell volume. Under resting conditions [Ca2+]i showed no apparent dependence on either potential or cell volume. After stimulating Ca2+ entry with carbachol (100 microM), [Ca2+]i increased with hyperpolarization (low-K+ or valinomycin treatment) and decreased with depolarization (high-K+ or gramicidin treatment) of the cell, as expected from changes in driving force for Ca2+ entry. In stimulated cells, hypotonic solutions caused [Ca2+]i to increase, whereas hypertonic solutions blocked Ca2+ entry. The shrinkage-induced decreases in [Ca2+]i were only slightly affected when the membrane potential was increased with valinomycin, suggesting that shrinkage directly affects the carbachol-activated Ca2+ conductance. In contrast, the swelling-induced increase in [Ca2+]i was significantly reduced in valinomycin-treated cells, suggesting an indirect dependence on a swelling-activated K+ conductance. Thus, carbachol-stimulated Ca2+ entry is under the dual control of membrane potential and cell volume. This mechanism may serve as a regulatory influence that determines the extent of Ca2+ influx during cholinergic stimulation.

Biological Transport↗