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Biomedical subjects

K Schmidt

Publications and source records attributed to K Schmidt.

At least 235 records · Page 13Linked to original sources
PubMed1996

Hydrogen oxidation by membranes from autotrophically grown Alcaligenes eutrophus H16: role of the cyanide-resistant pathway in energy transduction.

Eighty percent of the ATP and proton electrochemical gradient (-ZDeltapH) formed during H2 oxidation in membranes from autotrophically grown exponential-phase cells of Alcaligenes eutrophus H16 was derived from a redox pathway that includes the membrane-bound hydrogenase complex and the cyanide-resistant (bo-type) oxidase. The H2/ubiquinone-1 oxidoreductase activity was coupled to energy transduction and was fully inhibited by the quinone along 2-n-hepthyl-4-hydroxyquinoline-N-oxide. We conclude that the cytochrome-c-containing pathway in exponential-phase A. eutrophus H16 cells plays a minor role in energy conservation.

Alcaligenes↗
PubMed1996

Repetitive relationship themes in waking narratives and dreams.

The aims of the study were to see whether the core conflictual relationship theme (CCRT) measure can be reliably applied to dreams and to evaluate the degree to which the main components of the CCRT are present in both dreams and waking narratives in psychotherapy. For 13 psychoanalytic cases, the reliability of the CCRT was found to be good. Dreams and narratives were found to contain significant degrees of similarity in their CCRT components and similar and high level of negativity in both dreams and waking narratives. The results support the concept of a central relationship pattern that can be expressed in common in both waking narratives and dreams.

Adult↗
PubMed1996

A controlled study of microsurgical versus standard lumbar discectomy.

The purpose of the study was to evaluate whether a microsurgical discectomy (MS), compared with a standard lumbar discectomy (SD), could reduce the stay at the hospital or the postoperative morbidity. The study was prospective and of 79 patients with "virgin' lumbar radiculopathy from only one nerve root, 39 were randomized to MS and 40 to SD. All patients had positive myelography or CT findings. The fascia incision was 31 and 70 mm (p < 0.0001), respectively, but the skin incision was of the same length in both groups to blind the study. For the MS and SD group of patients, the median operation time was 48 and 35 min (p < 0.0001), and the stay at the hospital was 5.2 and 4.6 days, respectively. The two groups were not different in sex, age, localization or type of herniated discs. Use of analgesic medicine and the presence of pain in the back or legs pre- and postoperative was the same. We conclude that in a controlled and prospective study, reducing the fascia incision and the muscular dissection from a median of 70-31 mm, does not shorten the length of a stay at a hospital and it has no influence on postoperative morbidity.

Adult↗
PubMed1996

Inhibition of nitric oxide synthesis by NG-nitro-L-arginine methyl ester (L-NAME): requirement for bioactivation to the free acid, NG-nitro-L-arginine.

1. The L-arginine derivatives NG-nitro-L-arginine (L-NOARG) and NG-nitro-L-arginine methyl ester (L-NAME) have been widely used to inhibit constitutive NO synthase (NOS) in different biological systems. This work was carried out to investigate whether L-NAME is a direct inhibitor of NOS or requires preceding hydrolytic bioactivation to L-NOARG for inhibition of the enzyme. 2. A bolus of L-NAME and L-NOARG (0.25 micromol) increased coronary perfusion pressure of rat isolated hearts to the same extent (21 +/- 0.8 mmHg; n = 5), but the effect developed more rapidly following addition of L-NOARG than L-NAME (mean half-time: 0.7 vs 4.2 min). The time-dependent onset of the inhibitory effect of L-NAME was paralleled by the appearance of L-NOARG in the coronary effluent. 3. Freshly dissolved L-NAME was a 50 fold less potent inhibitor of purified brain NOS (mean IC50 = 70 microM) than L-NOARG (IC50 = 1.4 microM), but the apparent inhibitory potency of L-NAME approached that of L-NOARG upon prolonged incubation at neutral or alkaline pH. H.p.l.c. analyses revealed that NOS inhibition by L-NAME closely correlated with hydrolysis of the drug to L-NOARG. 4. Freshly dissolved L-NAME contained 2% of L-NOARG and was hydrolyzed with a half-life of 365 +/- 11.2 min in buffer (pH 7.4), 207 +/- 1.7 min in human plasma, and 29 +/- 2.2 min in whole blood (n = 3 in each case). When L-NAME was preincubated in plasma or buffer, inhibition of NOS was proportional to formation of L-NOARG, but in blood the inhibition was much less than expected from the rates of L-NAME hydrolysis. This was explained by accumulation of L-NOARG in blood cells. 5. These results suggest that L-NAME represents a prodrug lacking NOS inhibitory activity unless it is hydrolyzed to L-NOARG. Bioactivation of L-NAME proceeds at moderate rates in physiological buffers, but is markedly accelerated in tissues such as blood or vascular endothelium.

Animals↗
PubMed1996

Antisaccadic eye movements and attentional asymmetry in schizophrenia in three Pacific populations.

Antisaccadic eye movements were examined in 50 patients with schizophrenia and in 77 controls in three Pacific populations, namely New Zealand, Palau and Papua New Guinea. Despite the great biocultural variation encompassed by these three populations, schizophrenic patients made significantly more antisaccadic-errors than controls (36% vs. 13%), as has been demonstrated previously in other populations. This neurocognitive deficit may be consistent with frontal lobe dysfunction in schizophrenia. In addition, patients with schizophrenia made significantly more errors than expected when the target was presented in the right visual field (RVF). This trend was observed in patients from all three study areas, and was not seen in any of the control populations. Antisaccadic test performance in schizophrenia may be influenced by lateralized (left hemisphere) neuroanatomical impairment.

Adult↗
PubMed1996

Relation of stressors and depressive symptoms to clinical progression of viral illness.

OBJECTIVE: The aim of this research was to determine whether and in whom stressors and depressive symptoms facilitate clinical recurrence of herpes simplex virus (HSV) and progression of HIV. METHOD: Meta-analytic techniques were used to review the relations of stressors and depressive symptoms to clinical recurrence of HSV in 16 published studies and to indicators of HIV progression in 19 published studies. The authors calculated average effect sizes, performed fixed effect and random effect inferential analyses, tested for heterogeneous findings, and identified potential moderating variables. RESULTS: Depressive symptoms were associated with a slightly increased risk of HSV recurrence and increased reports of HIV-related symptoms, whereas stressors were not. However, depressive symptoms were not associated with objective indicators of accelerated HIV progression. Stressor studies, especially those that ascertained population-specific life events, found numerical and functional decrements in circulating natural killer cell populations. The candidate moderators identified include, for HSV recurrence, age, sex, and medication status, and for HIV-related symptoms, age, race, disease stage, and co-infection with HSV. CONCLUSIONS: Depressive symptoms, but not stressors, increase the risk of HSV recurrence generally. Depressive symptoms do not appear to accelerate HIV progression ubiquitously, although they are associated with increased reporting of HIV-related symptoms. Future studies that ascertain population-specific stressors should determine whether reductions in cytotoxic lymphocytes influence HIV disease progression. Moreover, researcher should investigate the role of the identified moderators and recognize psychoimmune moderators in existing and novel study groups. These analyses could confirm that certain individuals are especially susceptible to the effects on disease progression of stressors, depressive symptoms, or both.

Adult↗
PubMed1996

Normal distribution of apolipoprotein E alleles in progressive supranuclear palsy.

Apolipoprotein E (Apo E) genotype is a genetic risk factor influencing the development of Alzheimer's disease (AD). Progressive supranuclear palsy (PSP), like AD, is a dementing illness with neurofibrillary tangles. We determined the frequencies of Apo E alleles in 52 PSP patients and 52 age- and gender-matched controls. The distribution of Apo E allele frequencies and genotypes showed no difference between PSP and controls. Apo E allele status does not influence the development of PSP.

Aged↗
PubMed1996

Influence of dopaminergic transmission on severity of withdrawal syndrome in alcoholism.

OBJECTIVE: Dysfunction of dopaminergic transmission has been suggested as influencing withdrawal syndrome in alcohol-dependent patients. Therefore, dopamine levels and sensitivity of dopamine receptors were correlated with the severity of withdrawal syndrome in 40 alcoholics. METHOD: Dopamine blood plasma levels and apomorphine-induced Growth Hormone (GH) release were measured on the first day of detoxification (Day 1) and after 8 days of abstinence (Day 8). Severity of withdrawal syndrome was assessed daily by the Clinical Institute Withdrawal Assessment (CIWA) score. In the 22 patients (out of the 40) treated by chlormethiazole, severity of withdrawal was measured by the required chlormethiazole dose. RESULTS: A positive correlation was found between dopamine levels on Day 1 and the total CIWA score and necessary chlormethiazole dose, respectively. Correlation with the CIWA score was even stronger when the sensitivity of post-synaptic dopamine receptors was taken into account. No significant correlation between dopamine levels on Day 8 and withdrawal syndrome was found. CONCLUSIONS: Our findings indicate an influence of dopaminergic transmission on withdrawal syndrome during early withdrawal.

Adult↗
PubMed1996

Novel guanylyl cyclase inhibitor potently inhibits cyclic GMP accumulation in endothelial cells and relaxation of bovine pulmonary artery.

The aim of the present study was: 1) to determine the effects of the novel selective inhibitor of guanylyl cyclase, ODQ (1H-[1,2,4]oxadiazolo[4,3,-a]quinoxaline-1-one) on basal and agonist-stimulated cyclic GMP levels in cultured porcine aortic endothelial cells and bovine pulmonary artery strips; 2) to determine its effects on agonist-induced relaxations of bovine pulmonary artery strips; and 3) to compare pulmonary artery cyclic GMP levels with vessel relaxation. ODQ (1 nM-30 microM) inhibited cyclic GMP accumulation in endothelial cells stimulated with S-nitrosoglutathione, nitroprusside and 3-morpholine-sydnonimine at IC50 values of 40 to 100 nM. Complete suppression of cyclic GMP generation was observed at approximately 10 microM. Relaxation of pulmonary artery strips induced by S-nitrosoglutathione, nitroprusside, glycerol trinitrate, nitrite (all endothelium-independent), bradykinin and the Ca++ ionophore A23187 (endothelium-dependent) were antagonized by ODQ (1-10 microM) in a concentration-dependent way. A consistent feature of the inhibitor was that maximal relaxant effects also were reduced. Basal levels and agonist-induced increases in arterial tissue cyclic GMP were inhibited in the same concentration range. However, tissue cyclic GMP production correlated poorly with pulmonary artery relaxation in that relaxations induced by S-nitrosoglutathione were only inhibited in part (50%), whereas rises in cyclic GMP were abolished completely by ODQ (10 microM). Furthermore, at 1 microM, ODQ had no effect on relaxation induced by endothelium-dependent agonists, but prevented entirely stimulation of cyclic GMP accumulation in arterial tissue. These results suggest that ODQ inhibits nitrovasodilator-induced and endothelium-dependent relaxation through inhibition of guanylyl cyclase activation, but also point to the presence of a cyclic GMP-independent component of relaxation in bovine pulmonary artery.

Animals↗
PubMed1996

[Use of the ADH/REA method (Abbott Tdx-REA) in forensic blood alcohol determination].

The ethanol determination using the ADH/REA method (Abbott TDx-REA) is based on the principle of radiative energy attenuation (REA) applying the classic ADH-method. However, instead of measuring the extinction of the reaction product NADH, a chromogen formed by a coupled diaphorase reaction is measured. Serum, whole blood and urine are used for ethanol determination without prior treatment. The following analytical procedures such as sampling, addition of reagents and measuring are automated. Sample solutions of 100 to 200 microliters should be used. Daily calibration of the apparatus is recommended. Both precision and reproducibility meet the requirements of BAC-assays in forensic specimens. The results obtained by using gas chromatography and ADH/REA method show an excellent correlation (factor r = 0.9977). The ADH/REA method has proved to be a reliable assay procedure in routine determination of the BAC in forensic samples.

Accidents, Traffic↗
PubMed1996

Characterization of complex heart rate dynamics and their pharmacological disorders by non-linear prediction and special data transformations.

OBJECTIVE: The aim of the presented method was the characterization of different complex heart rate dynamics in conscious rabbits as well as during general anaesthesia and vagal blockade. This was done by non-linear prediction of original measured and special surrogate data in the phase space. METHOD: The development of the prediction error in dependence on the prediction time interval was investigated in the phase space. Two kinds of surrogate data were produced and tested with regard to non-linearities and orientation in the phase space. Typical characteristics of prediction error development were shown for simulated uncorrelated stochastic, correlated stochastic, regular deterministic, and deterministic chaotic signals. These characteristics were used to evaluate the measured heart rate data in connection with tests of surrogate data. RESULTS: It could be shown that heart rate fluctuation cannot be described by one of these ideal models alone. Common consideration of all investigated prediction characteristics indicated chaos in the heart rate of conscious rabbits as well as during anaesthesia and vagal blockade, where non-linear correlated stochastic properties could not be excluded. The different amount of non-linearities and orientation was described quantitatively. CONCLUSIONS: Detailed analysis of prediction error development in the phase space, connected with tests for non-linearities and orientation, enabled a specific quantitative characterization of complex heart rate dynamics and their pharmacological disorders.

Anesthesia, General↗
PubMed1996

Deterministic--chaotic and periodic properties of heart rate and arterial pressure fluctuations and their mediation in piglets.

OBJECTIVE: Only the simultaneous analysis of periodic and nonlinear properties of heart rate fluctuations (HRF) can describe completely this complex physiological process. Up to now there is, apart from a study of our own, no systematic and correlative investigation using both parameter groups, also not in early development. Thus, we tried to describe in this manner these properties of HRF, the corresponding mean arterial pressure fluctuations (MAPF) and respiratory movements (RM) and their mutual relations in neonatal pig. METHODS: In 6 term newborn piglets, periodic properties of HRF, RM, and MAPF were analyzed by spectral and coherence analysis, and deterministic-chaotic properties by calculation of correlation dimension (CD), Lyapunov exponent (LE), and construction of phase space plots. The assumption of deterministic chaotic components was supported by Theiler's test for nonlinearity, by always positive leading LEs, and by the results of a nonlinear deterministic model. These analyses were done in sleep states, general anaesthesia, hypoxic hypoxia, in ventilated state, and during cholinergic and additional beta-adrenergic blockade. RESULTS: In all experimental states, HRF and MAPF have periodic and nonlinear, very probably deterministic-chaotic properties, but in different relations. In anaesthetized piglets, periodic properties of HRF and MAPF dominate. In hypoxia the decreasing LE and CD of HRF and CD of MAPF were connected with increasing MAPF power density. Cholinergic blockade caused a decreased overall HRF and MAPF power and a decreasing LE and CD, but beta-adrenergic blockade decreased a small part of power density of both in 0.02-0.08 Hz only. The results of CD, LE, Theiler's test and the low dimensional deterministic model data suggested mainly deterministic-chaotic properties in the nonlinear part of HRF and MAPF. CONCLUSIONS: Already in neonatal piglets, both periodic and nonlinear, very probably deterministic chaotic properties of HRF and MAPF exist which change both during hypoxia and cholinergic blockade. They are partly cholinergically and--to a small extent--also beta-adrenergically mediated. The decrease of nonlinear complexity of HRF and MAPF during hypoxia suggests characteristic pathological change even in early development.

Anesthesia, General↗
PubMed1996

Characterization of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one as a heme-site inhibitor of nitric oxide-sensitive guanylyl cyclase.

Nitric oxide (NO) binds with high affinity to the heme of soluble guanylyl cyclase (sGC), resulting in accumulation of the second messenger cGMP in many biological systems. 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) was recently described as potent and selective inhibitor of sGC, providing an invaluable tool with which to settle the function of the cGMP pathway in NO-mediated signal transduction [Mol. Pharmacol. 48:184-188 (1995)]. The present study investigated the mechanism of ODQ-induced inhibition of purified bovine lung sGC. The drug induced a rightward shift of the concentration-response curves recorded with two different NO donors and a reduction of maximal sGC activity, pointing to a mixed type of inhibition. The time course of NO-stimulated sGC activity determined in the presence of 0.3 microM ODQ showed that the inhibitory effect was time-dependent (half-time approximately 3 min) and virtually complete after about 10 min. The cyclase did not recover from ODQ-induced inhibition upon extensive dilution, pointing to an apparently irreversible inactivation of the enzyme by the quinoxalin. Light absorbance spectroscopy showed that ODQ (0.3 mM) induced a shift of the Soret band of the heme from 431 nm to 393 nm, indicating that ODQ oxidizes the ferrous form of the enzyme to the ferric species, which is though to exhibit only poor NO sensitivity. Together, our results suggest that inhibition of sGC by ODQ is NO-competitive and results in an apparently irreversible oxidation of the prosthetic heme group.

Animals↗
PubMed1996

[Surgical resection of colorectal liver metastases: Gold standard for solitary and radically resectable lesions].

From 1960 to 1993, a total of 1.766 patients with liver metastases from colorectal carcinoma was recorded. Five-hundred-and-eight patients (28.8%) underwent hepatic resection which was performed with curative intent in 473 patients (26.8%). 30-day mortality in this group was 4.5%, being 2.6% (4 out of 155) since 1990. Significant morbidity was observed in 16% of patients with a decrease to 7% for the last 4 years. A 99.5 percent follow-up until January 1, 1996, was achieved. Excluding operative mortality there are 376 patients with "potentially curative" initial liver resection, and 65 corresponding patients with minimal macroscopic (n = 19) or microscopic (n = 46) residual disease. The latter group demonstrated a poor prognosis with median and maximum survival times of 14.8 and 56 months, respectively. Among the 376 patients having potentially curative resection the actuarial five, ten, and twenty year survival was 39 +/- 3, 26 +/- 5 and 21 +/- 13 percent, respectively. Tumor-free survival was 34 +/- 3 percent at 5 years. In the univariate analysis, the following factors were associated with decreased crude survival: Presence and extent of mesenteric lymph node involvement (p = 0.0001), poor grading of the primary tumor (p = 0.008), synchronous diagnosis of metastases (p = 0.004), satellite metastases (p < 0.0001), an increasing metastasis diameter (p < 0.0001), preoperative CEA elevation (p = 0.0002), a resection margin of less than 1 cm (p = 0.018), extrahepatic disease (p = 0.02), non-anatomical procedures (p = 0.008), and an operative blood loss exceeding 2.000 ml (p = 0.02). With respect to disease-free survival, extrahepatic disease (p = 0.09) failed to achieve statistical significance, while patients with colon cancer and with delayed resection of synchronous metastases did significantly better than those with rectal cancer (p = 0.02) and with a simultaneous procedure (p = 0.04), respectively. Multiplicity and bilobar involvement did not affect prognosis. Similarly, no significant predictive value of an increasing number of metastases (1-3 vs > or = 4) on either overall (p = 0.35) or disease free survival (p = 0.55) was found after a radical excision of all detectable disease. Using Cox's multivariate regression analysis, presence of satellite metastases, anatomical vs non-anatomical approach, primary tumor grade and diameter of the largest metastasis all independently affected both crude and tumor-free survival (p < 0.05). With respect to survival, this was complemented by the margin of clearance (0.05 < p < 0.1), while for disease-free survival primary tumor site and time of metastasis diagnosis had some additional influence. Twenty-six patients with R0-reresection of the liver, and 32 patients with radical excision of extrahepatic recurrent disease had a subsequent 5-year survival of 57 +/- 15 percent and 32 +/- 12 percent, respectively. This confirms the effectiveness of a close follow-up policy.

Adult↗