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Biomedical subjects

M Hartmann

Publications and source records attributed to M Hartmann.

At least 109 records · Page 6Linked to original sources
PubMed2001

Evaluation of subcutaneous tissue gases and pH during induction of acidosis and alkalosis. An experimental study in pigs.

Peripheral tissue oxygen utilization was studied during hypoxic-induced acidosis and sodium bicarbonate-induced alkalosis in 8 domestic pigs by measurements of subcutaneous oxygen tension (PscO2), carbon dioxide tension (PscCO2) and pH (pH(sc)) in relation to central hemodynamic parameters and oxygenation. Hypoxic-induced acidosis resulted in a decrease in P(sc)O(2) [corrected] and arterial oxygen tension (P(a)O(2)) to one third of baseline values (p < 0.05), an increase in PscCO2 and arterial carbon dioxide tension (PaCO2) from 41 to 55 and 34 to 39 mm Hg, respectively (p < 0.05), and a decrease in pH(sc) from 7.47 to 7.30 (p < 0.05). PscO2 and PaO2 increased during reversal of hypoxia and infusion of bicarbonate (p < 0.05), without reaching baseline values. In parallel PscCO2 decreased and pH(sc) increased but changes lagged behind changes in blood gases. Alkalosis established by further infusion of bicarbonate resulted in a decrease in PaO2 to 62 mm Hg whereas PscO2 remained below baseline values (p < 0.05). Correction of oxygen utilization in the subcutaneous tissue as measured by the markers PscCO2 and pH(sc) is slower than indicated by changes in tissue oxygen tension, blood gases and pH. Overcompensation of acidosis with bicarbonate resulting in alkalosis impairs oxygenation.

Acidosis↗
PubMed2001

Restricted diffusion within ring enhancement is not pathognomonic for brain abscess.

BACKGROUND AND PURPOSE: Recent experience suggests that diffusion-weighted MR imaging may be decisive in the differential diagnosis of ring-enhancing cerebral lesions. Whether restricted diffusion within a ring-enhancing cerebral mass lesion is pathognomonic for abscess was studied. METHODS: Seventeen patients with ring-enhancing cerebral lesions (three abscesses, six glioblastomas, eight metastases) on conventional contrast-enhanced T1-weighted images were examined with echo-planar diffusion-weighted MR imaging. Apparent diffusion coefficient (ADC) maps and the ADCs were calculated for all lesions. Lesions with signs of intralesional hemorrhage on unenhanced T1-weighted images were excluded. RESULTS: The central portion of all six glioblastomas and seven of eight metastases showed unrestricted diffusion, whereas two of three abscesses showed restricted diffusion (low ADC values) in their cavity. However, restricted diffusion also was found in one metastasis, and one abscess within a postoperative cavity showed unrestricted diffusion within a larger nondependent portion. CONCLUSION: In patients with ring-enhancing cerebral mass lesions, restricted diffusion might be characteristic but is not pathognomonic for abscess, as low ADC values also may be found in brain metastases.

Brain Abscess↗
PubMed2000

Ionic and acid gel formation of epimerised alginates; the effect of AlgE4.

AlgE4 is a mannuronan C5 epimerase converting homopolymeric sequences of mannuronate residues in alginates into mannuronate/guluronate alternating sequences. Treating alginates of different biological origin with AlgE4 resulted in different amounts of alternating sequences. Both ionically cross-linked alginate gels as well as alginic acid gels were prepared from the epimerised alginates. Gelling kinetics and gel equilibrium properties were recorded and compared to results obtained with the original non-epimerised alginates. An observed reduced elasticity of the alginic acid gels following epimerisation by AlgE4 seems to be explained by the generally increased acid solubility of the alternating sequences. Ionically (Ca(2+)) cross-linked gels made from epimerised alginates expressed a higher degree of syneresis compared to the native samples. An increase in the modulus of elasticity was observed in calcium saturated (diffusion set) gels whereas calcium limited, internally set alginate gels showed no change in elasticity. An increase in the sol-gel transitional rate of gels made from epimerised alginates was also observed. These results suggest an increased possibility of creating new junction zones in the epimerised alginate gel due to the increased mobility in the alginate chain segments caused by the less extended alternating sequences.

Alginates↗
PubMed2000

Effects of long-term nitroglycerin treatment on endothelial nitric oxide synthase (NOS III) gene expression, NOS III-mediated superoxide production, and vascular NO bioavailability.

Long-term nitroglycerin (NTG) treatment has been shown to be associated with cross-tolerance to endothelium-dependent vasodilators. It may involve increased production of reactive oxygen species (such as superoxide, O(2)(.-)) that rapidly inactivate the nitric oxide (NO) released from the endothelial cells. It remains to be elucidated, however, whether long-term treatment with NTG alters the activity and expression of the endothelial NO synthase (NOS III) and whether this enzyme can contribute to O(2)(.-) formation. We studied the influence of long-term NTG treatment on the expression of NOS III as assessed by RNase protection assay and Western blot. Tolerance was measured ex vivo in organ chamber experiments with rat aortic rings. O(2)(.-) and NO formation were quantified using lucigenin- and Cypridina luciferin analog-enhanced chemiluminescence as well as electron spin resonance (ESR) spectroscopy. Treatment of Wistar rats with NTG (Alzet osmotic minipumps, NTG concentration 10 microg x kg(-1) x min(-1)) for 3 days caused marked tolerance, cross-tolerance to the endothelium-dependent vasodilator acetylcholine, and a significant increase in O(2)(.-)-induced chemiluminescence. Tolerance was associated with a significant increase in NOS III mRNA to 236+/-28% and NOS III protein to 239+/-17%. In control vessels, the NOS inhibitor N(G)-nitro-L-arginine (L-NNA) increased the O(2)(.-)-mediated chemiluminescence, indicating that basal production of endothelium-derived NO depresses the baseline chemiluminescence signal. In the setting of tolerance, however, L-NNA decreased steady-state O(2)(.-) levels, indicating the involvement of NOS III in O(2)(.-) formation. Likewise, A23187-induced, NOS III-mediated O(2)(.-) production was more pronounced in tolerant than in control vessels. Vascular NO bioavailability as assessed with ESR spectroscopy using iron-thiocarbamate as a trap for NO was significantly reduced in tolerant vessels. Pretreatment of tolerant tissue in vitro with the protein kinase C (PKC) inhibitors reduced basal and stimulated NOS III-mediated O(2)(.-) production and partially reversed vascular tolerance. These findings suggest that NTG treatment increases the expression of a dysfunctional NOS III gene, leading to increased formation of O(2)(.-) and decreased vascular NO bioavailability. Normalization of NOS III-mediated O(2)(. -) production and improvement of tolerance with PKC inhibition suggests an important role for PKC isoforms in mediating vascular dysfunction caused by long-term NTG treatment.

Acetylcholine↗
PubMed2000

[Interdisciplinary consensus on diagnosis and therapy of testicular tumors. Results of an update conference based on evidence-based medicine. German Testicular Cancer study Group (GTCSG)].

BACKGROUND: An "Interdisciplinary Consensus Statement on the Diagnosis and Therapy of Testicular Tumors" was prepared in 1996 by the "Interdisciplinary Testicular Tumor Working Group" (IAH) with input from representatives from diagnostic and therapeutic disciplines of various working groups of the German Cancer Society (Strahlenther Onkol 1997;173:397-406). In 1998 the IAH met again together with the "Testicular Tumor Working Party" of the Urooncology Working Group (AUO) and formed the "German Testicular Cancer Study Group" (GTCSG). Defined and accepted interdisciplinary standards from the initial meeting were revised based on current scientific developments and clinical results. This cooperating effort increased the quality of the initial recommendations and helped to put the recommendations for diagnosing and treating testicular tumor on a broader scientific basis. METHODS: According to the principles of "evidence-based medicine" (EBM), the Consensus from 1996 was modified, based on the current level of evidence from the published literature. The methodological process and evaluation criteria used were that of the "Cochrane Collaboration". RESULTS: An "Interdisciplinary Update Consensus Statement" summarizes and defines the diagnostic and therapeutic standards according to the current scientific practices in testicular cancer. For 21 separate areas scientifically based decision criteria are suggested. For treatment areas where more than one option exist without a consensus being reached for a preferred strategy, such as in seminoma in clinical Stage I or in non-seminoma Stages CS I or CS IIA/B, all acceptable alternative strategies with their respective advantages and disadvantages are presented. This "Interdisciplinary Update Consensus" was presented at the 24th National Congress of the German Cancer Society on March 21st and subsequently evaluated and approved by the various German scientific medical societies.

Evidence-Based Medicine↗
PubMed2000

[Lipodystrophy syndrome in HIV infection].

Since the availability of protease inhibitors in 1997, there has been a great change in antiretroviral therapy but also new long term side effects have emerged, mainly metabolic changes such as hypertriglyceridemia, hypercholesteremia and hyperglycemia. Besides, fat redistribution has been observed. Fat wastes in the face and limbs but accumulates in the adipose tissue of the dorsocervical and abdominal region and the breasts. The mechanism of these changes remains unclear. For therapy a protease inhibitor free therapy or lipid lowering drugs may be tried. 29 of our 224 patients developed lipodystrophy. 27 of these patients had been treated with a protease inhibitor (17 patients with indinavir); 2 of the patients had never received protease inhibitors.

Female↗
PubMed2000

[Hashimoto encephalopathy: steroid-sensitive encephalopathy in Hashimoto thyroiditis].

Hashimoto's encephalopathy is a steroid-responsive, relapsing or progressive encephalopathy associated with Hashimoto's thyroiditis. Characteristic clinical features are confusion, seizures, alteration in conscious level, stroke-like episodes, myoclonus, and tremulousness. High CSF protein levels without pleocytosis and a diffusely abnormal EEG are typical findings. Brain CT and MRI and cerebral angiogram are usually normal. We present two case reports of Hashimoto's encephalopathy in 55- and 77-year-old patients who both responded well to steroid therapy, and review the literature.

Aged↗
PubMed2000

Pharmacology of a selective cyclooxygenase-2 inhibitor, HN-56249: a novel compound exhibiting a marked preference for the human enzyme in intact cells.

HN-56249 (3-(2,4-dichlorothiophenoxy)-4-methylsulfonylamino-benzenesu lfonamide), a highly selective cyclooxygenase (COX)-2 inhibitor, is the prototype of a novel series of COX inhibitors comprising bicyclic arylethersulfonamides; of this series HN-56249 is the most potent and selective human COX-2 inhibitor. HN-56249 inhibited platelet aggregation as a measure of COX-1 activity only moderately (IC50 26.5+/-1.7 microM). In LPS-stimulated monocytic cells the release of prostaglandin (PG) F1alpha as a measure of COX-2 was markedly inhibited (IC50 0.027+/-0.001 microM). Thus, HN-56249 showed an approximately 1000-fold selectivity for COX-2 in intact cells. In whole blood assays HN-56249 showed a potent inhibitory activity for COX-2 (IC50 0.78+/-0.37 microM) only. COX-1 was only weakly inhibited (IC50 867+/-181 microM). Hence, HN-56249 exhibited a greater than 1000-fold selectivity for whole blood COX-2. HN-56249 surpassed the COX-2 selectivities of the COX-2 selective inhibitors 3-cyclohexyloxy-4-methylsulfonylamino-nitrobenzene (NS-398) and 6-(2,4-difluorophenoxy)-5-methyl-sulfonylamino-1-indanone (flosulide) in the intact cell assays by eight- and threefold, respectively, and in the whole blood assays by approximately 40-fold. Following i.v. administration HN-56249 inhibited carrageenan-induced rat paw oedema only moderately (ID50 26.2+/-5.7 mg/kg, mean +/- SEM), approximately tenfold less potent than indomethacin (ID50 2.1+/-0.2 mg/kg, mean +/- SEM). After oral administration HN-56249 reversed thermal hyperalgesia in the carrageenan-induced rat paw oedema test, however, some 30-fold less potently than diclofenac. Comparing the inhibitory potency of HN-56249 against human COX-2 with that against murine COX-2 in intact cells revealed a 300-fold selectivity for the human enzyme. Similar effects were observed with other COX-2-selective arylethersulfonamides. In contrast, non-COX-2-selective arylethersulfonamides, including a highly selective COX-1 inhibitor, inhibited human and murine COX-2 approximately equipotently. In conclusion, HN-56249 is a novel potent and highly selective COX-2 inhibitor with a marked preference for the human COX-2 enzyme in vitro. Despite excellent bioavailability and the long plasma half-life of HN-56249, anti-inflammatory effects in rodents were only moderate. We suggest these differing in vitro-in vivo effects observed could be due to significant inflammatory prostaglandin synthesis by COX-1, or to the genetic differences between human and rodent COX-2, or to both.

Animals↗
PubMed2000

Screening for and characterization of phospholipase A1 hypersecretory mutants of Tetrahymena thermophila.

We have described a procedure for the isolation of mutants of Tetrahymena thermophila with hypersecretion of phospholipase A1 (PLA1). Using random chemical mutagenesis, uniparental cytogamy, genetic crossing and a new, fast and effective screening procedure, four PLA1-hypersecretory mutants were isolated. The screening procedure is based on the formation of a halo appearing around cylindrical holes in a lecithin-containing agar plate filled with cell-free supernatants. About 3,940 clones were tested with this procedure in primary screening for hypersecretory features, of which 60 putative hypersecretory mutants were isolated, subcloned and tested in a secondary screening. Of these, four selected mutants showed 1.8-2.2 more PLA1 activity in the cell-free supernatants compared to the wild-type strain CU 438.1. Hypersecretion was only observable for PLA1; no increased activity for two other lysosomal enzymes could be detected. These hypersecretory mutants of T. thermophila can be very useful for increasing the yield of PLA1 in fermentation processes. This is particularly relevant because, in contrast to other phospholipases, PLA1 is not available on the commercial market for fine chemicals and little is known about the role of PLA1 in cell signaling and metabolism.

Animals↗
PubMed2000

[Health care utilization in patients with Fibromyalgia Syndrome (FMS)].

BACKGROUND: The purpose of the study was to examine the pain related health care utilization in patients with fibromyalgia syndrome. METHODS: In a multicenter study six rheumatological hospitals associated in the rheumatological center of Heidelberg participated. All consecutive patients which fulfilled the ACR-criteria of fibromyalgia were assessed. Data about pain and related treatments were available from n=259 patients. RESULTS: Patients suffered from chronic generalized pain on average for 5 years before being diagnosed as fibromyalgia. In most of the cases longlasting localized pain symptoms preceeded generalized pain. The spectrum of pain related treatments seems to be wide and arbitrary: 87% took questionable or excessive medication. 86% had some form of physiotherapy and 41% already experienced psychological treatment. 28% of the patients consulted dental surgeons including teeth extraction and 20% underwent multiple orthopaedic surgery. A mean of five different health care professionals were consulted regarding the pain problem. Treatment satisfaction rated by the patients was lowest with pharmacological and highest with psychological treatment and physiotherapy. CONCLUSIONS: The health care-seeking behavior of fibromyalgia-patients seems to be characterized by a multitude of different treatment attempts. Treatment was often invasive and focused on localized symptoms rather than on the generalized pain syndrome. An early confirmation of the diagnosis and a more evidence based treatment is strongly indicated.

English Abstract↗
PubMed2000

Effects of a nitrate-free interval on tolerance, vasoconstrictor sensitivity and vascular superoxide production.

OBJECTIVES: In the present study, we tested whether a nitrate-free interval is able to prevent increases in vascular superoxide (O2*-) and the development of hypersensitivity to vasoconstrictors and whether this may result in restoration of vascular nitroglycerin (NTG) sensitivity. BACKGROUND: Intermittent NTG-patch treatment (12 h patch on/patch-off) has been shown to increase ischemic periods in patients with stable coronary arteries, suggesting a rebound-like situation during the patch-off period. Recently, we demonstrated that long-term treatment with NTG induces tolerance, which was in part related to increases in vascular O2*- and increased vasoconstrictor sensitivity. METHODS: New Zealand white rabbits received a continuous application of NTG patches (0.4 mg/h) or an intermittent application of NTG patches (12 h patch on, 12 h patch off) for three days. Isometric tension studies were performed with aortic rings, and vascular O2*- was estimated using lucigenin-derived chemiluminescence (5 micromol/liter). Expression of the copper/zinc (Cu/Zn) superoxide dismutase (SOD) was assessed by Western blotting, and SOD activity was measured by autooxidation of 6-hydroxydopamine. RESULTS: Continuous treatment with NTG caused tolerance to NTG, cross-tolerance to the endothelium-dependent vasodilator acetylcholine, increased vascular O2*-, reduced Cu/Zn SOD expression and increased sensitivity to vasoconstrictors such as phenylephrine, serotonin and angiotensin II. On/off treatment with NTG improved tolerance, corrected endothelial dysfunction and decreased vascular O2*-. In addition the reduction in SOD expression was less pronounced, whereas increases in the sensitivity to vasoconstrictors such as phenylephrine and serotonin remained nearly unchanged. CONCLUSIONS: Enhanced vasoconstrictor sensitivity may explain, at least in part, the rebound phenomena observed in patients during a 12-h NTG patch-off period.

Acetylcholine↗
PubMed2000

Epimerization of nonnatural uronans with mannuronan C-5-epimerases to obtain alginatelike polysaccharides.

Different polysaccharides containing D-mannose residues have been C-6-oxidized by a selective TEMPO-mediated hypohalite oxidation to obtain the corresponding uronans. These have been treated with various recombinant mannuronan C-5-epimerases and the resulting products were analyzed by 1H NMR spectroscopy. Oxidized konjac mannan could be epimerized to obtain a uronan with a content of about 12% alpha-L-gulopyranuronate (G) residues. On prolonged epimerization, beta-elimination was observed. The oxidized galactomannan locust bean gum could only be scarcely epimerized, probably due to steric effects exerted by its 26% alpha-D-galacturopyranosyl side groups. Oxidized, galactose-depleted guar gum with a alpha-D-galactosyl content of 11% could be epimerized to a G content of about 15%. With oxidized cellulose as a substrate, mainly beta-elimination was observed. It thus seems that the mannuronan C-5-epimerases employed recognize glucuronate residues and abstract proton-5 but are unable to perform the second epimerization step and instead yield beta-eliminated products.

Alginates↗
PubMed2000

[Is perfusion MRI feasible in lesions with disrupted blood-brain barrier? Pitfalls and possible solutions].

AIM: When using perfusion-weighted magnetic resonance imaging (MRI) in lesions with blood-brain barrier (BBB) disruption two methods are normally applied to eliminate the influence of contrast material uptake on T2* dynamics: injection of contrast agent before starting perfusion imaging (pre-injection) and simultaneous acquisition of T1- and T2*-dynamics using a dual echo (DE)-FLASH sequence. The purpose of this study was to examine both methods with regard to their reliability. MATERIAL AND METHODS: We performed four perfusion measurements in a patient with a primary cerebral lymphoma located in the corpus callosum: two measurements with a DE-FLASH sequence and two measurements with a gradient-echo echo-planar-imaging (GE-EPI) sequence, respectively. In both cases there was one measurement with and one without pre-injection of contrast material. RESULTS: Pre-injection of contrast material reduced the influence of T1 and allowed us to monitor the transient signal drop when using the GE-EPI sequence. Analysis of the time-course of DE-FLASH, however, showed that there was still a T1 decrease even after pre-injection. After the first pass the T2*-dynamics showed a distinct long-term T2*-decrease. DISCUSSION: Neither pre-injection nor DE-FLASH allow us to eliminate the effects of contrast agent uptake completely. Both methods, however, increase the reliability of perfusion MRI. Their efficacy depends on the extent of the BBB disruption.

Aged↗
PubMed2000

The role of psychosocial factors in fibromyalgia syndrome.

OBJECTIVE: The main objective of this review was to evaluate the role of psychosocial factors in the development of fibromyalgia syndrome. METHOD: Review of the literature concerning the influence of psychosocial factors. RESULTS: In fibromyalgia syndrome psychosocial factors are relevant at different etiological levels. They can be classified into predisposing, triggering and stabilising/"chronifying" factors. CONCLUSION: Due to the increasing knowledge about the influence of psychosocial factors for the development of fibromyalgia, the biomedical model has to be expanded to a biopsychosocial model. The biopsychosocial concept has an impact on the therapeutic approach. Strong evidence for the model is provided by the good results of interdisciplinary treatment studies.

Disease Susceptibility↗
PubMed2000

The psychosocial outcome of adolescent-onset schizophrenia: a 12-year followup.

This study examines the educational/occupational outcome and social situation of patients treated for schizophrenia in adolescence (age at admission 11.5-17.9 years; mean 16.0 years). Out of 96 consecutively admitted patients between 1976 and 1987, 85 (89%) could be traced and 65 (68%) were reassessed more than 10 years after the first episode. At followup, 54 of the 65 (83%) had had at least one further inpatient-treated episode and 48 (74%) were receiving psychiatric treatment. Thirty-seven (57%) of the subjects were at least moderately impaired with respect to vocational functions (i.e., did not achieve their premorbid educational/occupational goals). Serious social disability was found in 42 (66%) of the 64 subjects for whom social disability data were available. Regarding means of maintenance, 49 (75%) were financially dependent, supported by parents or public assistance. Impairments were comparable for males and females. History of treatment (longer duration of inpatient stay; more than two inpatient episodes) was found to be predictive of lower vocational functioning at followup. Severity of positive symptoms and more than two inpatient episodes in the early course of illness predicted social disabilities in young adulthood. Findings support the view that, because of early onset, the long-term perspective for many adolescent-onset schizophrenia patients is that of poor social adjustment, severe functional impairment, and high socioeconomic dependence and suggest that consequences are more severe than in adult-onset schizophrenia.

Acute Disease↗