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Biomedical subjects

M Hartmann

Publications and source records attributed to M Hartmann.

At least 127 records · Page 7Linked to original sources

Family perception of interpersonal behavior as a predictor in eating disorders: a prospective, six-year followup study.

This study assessed family perception patterns of interpersonal behavior in families with a daughter diagnosed with an eating disorder 6 years after treatment that used a prospective design. Family perception patterns of patients found to have a poor outcome at followup (n = 15) were compared with patients with a good outcome (n = 23), as well as a control group (n = 36). Using the system of multiple level observation of groups (SYMLOG), all 238 family members evaluated themselves and each other. The index patients with a poor outcome perceived themselves as friendlier and more positive than they were perceived by their families. In comparison to parents of daughters with a good outcome and the control group, parents of daughters in the poor outcome group perceived themselves to be less friendly than their partners perceived them to be. A rigid polarization of the perception of the index patient by family members and a discrepancy in this perception between the index patient and the rest of the family were found to be indicative of a poor prognosis. Implications for treatment based on family perception patterns of interpersonal behavior are discussed.

Adolescent↗

Production of basic fibroblast growth factor and interleukin 6 by human smooth muscle cells following infection with Chlamydia pneumoniae.

Chlamydia pneumoniae infection has been associated with asthma and atherosclerosis. Smooth muscle cells represent host cells for chlamydiae during chronic infection. In this study we demonstrated that C. pneumoniae infection of human smooth muscle cells in vitro increased production of interleukin 6 (IL-6) and basic fibroblast growth factor (bFGF) as shown by reverse transcription-PCR, immunoblotting, and enzyme-linked immunosorbent assay. In contrast, levels of platelet-derived growth factor A-chain mRNA were not affected after infection. The stimulation of bFGF and IL-6 production was most effective when viable chlamydiae were used as inoculum. Furthermore, inhibition of bacterial protein synthesis with chloramphenicol prevented up-regulation of IL-6 and bFGF in infected cells. Addition of IL-6 antibody to infected cultures diminished bFGF expression, indicating involvement of produced IL-6. These findings suggest that chlamydial infection of smooth muscle cells elicits a cytokine response that may contribute to structural remodeling of the airway wall in chronic asthma and to fibrous plaque formation in atherosclerosis.

Arteriosclerosis↗

Influence of positive end-expiratory pressure ventilation on peripheral tissue perfusion evaluated by measurements of tissue gases and pH. An experimental study in pigs with oleic acid lung injury. .

UNLABELLED: Measurements of subcutaneous oxygen tension (PscO(2)), subcutaneous carbon dioxide tension (PscCO(2)) and subcutaneous pH (pHsc) were used for evaluation of peripheral oxygenation in pigs subjected to oleic acid-induced lung injury during ventilation with increasing levels of positive end-expiratory pressure (PEEP). Lung injury resulted in a decrease of arterial oxygen tension (PaO(2)) from 93 to 37 mm Hg (p<0.01) with maintained cardiac output. PscO(2) decreased from 45 to 17 mm Hg (p<0.01) and pHsc from 7.47 to 7.39 (p<0.05), and PscCO(2) increased from 46 to 59 mm Hg (p<0.05). Increase of PEEP level between 5 and 20 cm H(2)O resulted in a continuous increase of PaO(2) from 45 to 145 mm Hg and a decrease of cardiac output from 4.1 to 2.0 liters/min (p<0.01). PscO(2) increased up to a PEEP level of 15 cm H(2)O, reaching 26 mm Hg. Further increase of PEEP level up to 20 cm H(2)O resulted in an increase of PscCO(2) from 65 to 71 mm Hg (p<0.05) and a decrease of pHsc from 7.31 to 7.29 (p<0.05). IN CONCLUSION: measurements of tissue gases and pH can be used to evaluate optimum peripheral tissue oxygenation during titration of PEEP level. Whether these measurements can be used as the only indicator to guide therapy in an individual case remains to be studied.

Animals↗

RPLND or primary chemotherapy in clinical stage IIA/B nonseminomatous germ cell tumors? Results of a prospective multicenter trial including quality of life assessment.

BACKGROUND: In order to reduce therapy-related morbidity in patients with nonseminomatous testicular germ cell tumors in clinical stage IIA/B, we performed a prospective multicenter trial comparing the standard retroperitoneal lymph node dissection (RPLND) +2 cycles of chemotherapy (arm A) with 3-4 cycles of primary chemotherapy (arm B). METHODS: From February 1991 to July 1995, 57 participating centers from Germany and Austria recruited 187 evaluable patients. 109 received primary RPLND and 78 primary chemotherapy. Two different chemotherapies were applied (PEB and CEB as adjuvant or inductive treatment). The quality of life (QoL), therapy-related morbidity, suspected predictive factors (histology and size of metastases), and outcome were assessed. RESULTS: In arm A, 12% had pathological stage (PS) I, 70% PS II A/B, and 18% PS II C/III. In arm B, 67% achieved complete remission with chemotherapy alone, 33% required a secondary RPLND. After a median follow-up of 36 months, 7% of the patients in arm A and 11% in arm B had relapsed. Two patients died due to complications of chemotherapy. Surgical complications amounted to 12% in arm A and 27% of 26 postchemotherapy RPLNDs (9% in arm B). Loss of ejaculation occurred in 32% in arm A, and 16% in arm B. Acute toxicity of chemotherapy was higher in the group receiving primary chemotherapy. CONCLUSION: We recommend primary RPLND because adjuvant chemotherapy can be spared in PS I, two cycles of chemotherapy are less toxic than 3 or 4 cycles, the primary operation is associated with less complications than that following chemotherapy and, with modern surgical procedures, ejaculation can be preserved in most of the patients, provided that the operation is carried out by an experienced surgeon. No statistically significant differences in the QoL outcome occurred between the treatment groups, suggesting that chemotherapy alone is not superior to primary or secondary RPLND in this respect.

Antineoplastic Combined Chemotherapy Protocols↗

Determination of 17-hydroxyprogesterone in plasma by stable isotope dilution/benchtop liquid chromatography-tandem mass spectrometry.

An assay based on stable isotope dilution liquid chromatography-tandem mass spectrometry (ID/LC-MS-MS) was developed for the quantification of 17-hydroxyprogesterone, the most important indicator of 21-hydroxylase deficiency in human plasma. Plasma was extracted using ethyl acetate and Extrelut columns. LC was performed on a reversed-phase C18 column using a water/methanol gradient. A benchtop triple quadrupole mass spectrometer, operating in selected reaction monitoring mode, served as mass detector. The analytical run time was 9 min per sample. The sensitivity was high: 0.06 pmol of 17-hydroxyprogesterone yielded a signal-to-noise ratio of 13. Precision (CV) and accuracy (relative error) derived from the analyses of unspiked and spiked validation samples were 7.4-12.0% and 6.4%, respectively. When analyzing the same samples - median (range), in nanomoles per liter - from neonates and adults independently by ID/LC-MS-MS as well as by ID/gas chromatography (GC)-MS, corresponding results were obtained: neonates (n = 10), ID/LC-MS-MS 3.99 (0.48-16.05), ID/GC-MS 5.39 (1.57-13.02); adults (n = 10), ID/LC-MS-MS 2.66 (1.39-6.15), ID/GC-MS 2.54 (0.51-5.12). The technique permitted reliable detection of classical and nonclassical forms of 21- hydroxylase deficiency. The much simpler sample preparation, the faster analytical run time and the operational ease possible with ID/LC-MS-MS permit a considerable increase of sample testing per day without compromising on analytical sensitivity and specificity. We expect that benchtop tandem mass spectrometry will open new avenues in clinical steroid analysis.

17-alpha-Hydroxyprogesterone↗

Hormonal diagnosis of 21-hydroxylase deficiency in plasma and urine of neonates using benchtop gas chromatography-mass spectrometry.

We aimed at measuring the first plasma concentrations of 17-hydroxyprogesterone (17OH-P) determined by benchtop isotope dilution/gas chromatography-mass spectrometry (ID/GC-MS) in term neonates with or without 21-hydroxylase deficiency. Plasma samples from normal cord blood specimens (n=30), unaffected neonates (n=38) and neonatal patients with classical 21-hydroxylase deficiency (eight salt-wasters, three simple virilizers) were analyzed. Steroid profiling of random urinary specimens by GC-MS served as a confirmatory test for 21-hydroxylase deficiency. 17OH-P (nmol/l) in cord blood plasma lay between 11.66 and 75.92 (median 24.74). It declined shortly after birth. In the first 8 days of life, the time that screening for 21-hydroxylase deficiency is performed, 17OH-P ranged between undetected levels and an upper limit of 22.87 (median 4.11). Thereafter (days 9-28) its concentrations lay between 2.18 and 20.30 (median 6.22). Except one simple virilizer, all other patients with 21-hydroxylase deficiency had clearly elevated plasma 17OH-P at the time that screening for 21-hydroxylase deficiency would be performed. We suggest ID/GC-MS, which provides the highest specificity in steroid analysis, for checking suspicious concentrations of 17OH-P in neonates and underscore the potential of urinary steroid profiling by GC-MS as a rapid, non-invasive and non-selective confirmatory test for congenital adrenal hyperplasia.

17-alpha-Hydroxyprogesterone↗

MRI of acute experimental intracerebral hematoma.

The purpose of the study was to evaluate the ability of different MR-sequences to detect and delineate experimentally produced hyperacute intracerebral hematomas in rats. Twenty male Sprague-Dawley rats received a unilateral hematoma of various volumes by stereotactic injection of fresh autologous arterial blood into the right caudatoputamen. MRI was performed up to 30 min after-generation of each hematoma. We obtained coronal T2- and T1-weighted spin-echo images. Furthermore we acquired RF-spoiled 2D- and 3D-FLASH images. MR-images were evaluated for signal behavior, location, configuration, size, and volume of each hematoma on a dedicated work station. MR volumetry was correlated to volumetric data obtained from the serial stained histological sections. All hematomas produced signal abnormalities on all sequences in each case. In the majority of cases the hematomas were hypointense. RF-spoiled FLASH 2D- and 3D-sequences showed the best detection of the hematoma owing to their high sensitivity to susceptibility effects. The best correlation between MR- and histological volumetry was found on RF-spoiled FLASH 2D- (corr. 0.81), SE T2- (corr. 0.79), and T1- (corr. 0.74) weighted images. The lowest correlation index was found on the RF-spoiled FLASH 3D-images (corr. 0.51). Signal loss of hematomas on gradient-echo images and--to a lesser extent--spin-echo T2-weighted images due to susceptibility effects can reliably delineate an acute state, whereas conventional MR scans of ischemic stroke may be normal. MRI may thus be the imaging modality of choice in patients with acute brain attack, especially when it is planned to perform diffusion and perfusion MRI before thrombolytic therapy.

Acute Disease↗

Risk factors for relapse in stage I non-seminomatous germ-cell tumors: preliminary results of the German Multicenter Trial. German Testicular Cancer Study Group.

Risk factor analysis to identify low-risk patients for occult metastatic disease (vascular invasion, percentage embryonal carcinoma, MIB-I proliferation rate) yields reliable results if performed by experts. A correct prediction is possible at the 90% level. Similar accuracy, however, may be achieved if the computed tomography (CT) staging is optimized and the evaluation performed by an experienced investigator. The combination of both methods (biological risk factor analysis and CT staging) may virtually exclude the risk of relapse in a limited number of patients. However, so far, no risk factor that is able to reliably predict occult metastatic disease or relapse in clinical state I patients has been identified in prospective trials. The preliminary results of the current German Multicenter Trial suggest an inferior value of prediction for low-risk patients if risk factor analysis and/or CT staging is performed in non-specialized centers.

Antineoplastic Combined Chemotherapy Protocols↗

The efficacy of a risk factor-based cognitive behavioral intervention and electromyographic biofeedback in patients with acute sciatic pain. An attempt to prevent chronicity.

STUDY DESIGN: An investigation of the efficacy of an individually scheduled, risk factor-based cognitive behavioral therapy and a standardized electromyographic biofeedback intervention in the prevention of chronicity in patients with acute sciatica and psychosocial risk factors for chronicity. OBJECTIVES: To investigate the possibility of enhancing pain relief and preventing chronicity in patients with acute sciatica, based on a screening for psychosocial high-risk factors of chronification. SUMMARY OF BACKGROUND DATA: Psychological interventions were evaluated mainly in patients with chronic low back pain. Numerous randomized trials have demonstrated their efficacy, whereas the amount of pain relief was found to be marginal. METHODS: Subjective and behavioral outcome parameters were compared with the respective parameters in age-, gender-, and diagnosis-matched high- and low-risk patients. No additional behavioral treatment for in-patient medical therapy was offered to the patients. Outcome of these patients also was compared with that of a group of refusers of behavioral therapy. Psychological, functional, and behavioral variables were measured before and after treatment and at 3-, 6-, 12- and 18-month follow-up visits. Changes over time, group differences, and possible group x time interactions were analyzed by analysis of variance and nonparameteric comparisons. RESULTS: Data analysis showed a statistically and clinically significant, beneficial effect of both behavioral interventions. However, risk factor-based cognitive behavioral therapy was superior to electromyographic biofeedback intervention with respect to pain relief and application for early retirement. The cognitive behavioral therapy showed a similar good outcome (e.g., 90% showed a clinical significant pain reduction) as the low-risk patients (83% pain reduction). High risk patients and refusers of therapy showed a poor outcome in pain (33% and 20% pain reduction, respectively), disability, and work performance. CONCLUSIONS: Individually scheduled, risk factor-based cognitive behavior therapy could be a beneficial treatment modality, which can be offered, in addition to a medical treatment, to patients with acute sciatica and psychosocial high risk factors for chronicity. It may be an effective way to prevent chronification in these patients.

Acute Disease↗

S100A12 is expressed exclusively by granulocytes and acts independently from MRP8 and MRP14.

Changes in cytosolic calcium concentrations regulate a wide variety of cellular processes, and calcium-binding proteins are the key molecules in signal transduction, differentiation, and cell cycle control. S100A12, a recently described member of the S100 protein family, has been shown to be coexpressed in granulocytes and monocytes together with two other S100 proteins, MRP8 (S100A8) and MRP14 (S100A9), and a functional relationship between these three S100 proteins has been suggested. Using Western blotting, calcium overlays, intracellular flow cytometry, and cytospin preparations, we demonstrate that S100A12 expression in leukocytes is specifically restricted to granulocytes and that S100A12 represents one of the major calcium-binding proteins in these cells. S100A12, MRP8, and MRP14 translocate simultaneously from the cytosol to cytoskeletal and membrane structures in a calcium-dependent manner. However, no evidence for direct protein-protein interactions of S100A12 with either MRP8 or MRP14 or the heterodimer was found by chemical cross-linking, density gradient centrifugation, mass spectrometric measurements, or yeast two hybrid detection. Thus, S100A12 acts individually during calcium-dependent signaling, independent of MRP8, MRP14, and the heterodimer MRP8/MRP14. This granulocyte-specific signal transduction pathway may offer attractive targets for therapeutic intervention with exaggerated granulocyte activity in pathological states.

Antigens, Differentiation↗

The breast cancer-associated MUC1 gene generates both a receptor and its cognate binding protein.

MUC1 proteins, some of which contain a mucin-like domain and others lacking this region, can be generated from the human breast cancer-associated MUC1 gene by alternative splicing. The MUC1/Y isoform is devoid of the mucin domain and is a cell membrane protein that undergoes transphosphorylation on both serine and tyrosine residues. We have identified cognate binding proteins that specifically interact with the extracellular domain of MUC1/Y. Coimmunoprecipitation analyses clearly revealed the presence of complexes composed of MUC1/Y and its cognate binding proteins in primary breast tumor tissue. MUC1/Y-expressing mammary tumor cells can be specifically targeted, in vivo, with the labeled cognate binding protein. The k(D) of MUC1/Y for its binding proteins was estimated as 1.2 nM. The MUC1/Y binding proteins are also derived from the MUC1 gene and represent the secreted mucin-like polymorphic MUC1 proteins MUC1/SEC and MUC1/REP, which contain a tandem repeat array. Whereas nonposttranslationally modified MUC1/Y bound efficiently to MUC1/SEC, the latter mucin-like protein had to be posttranslationally modified in a cell-type specific manner to bind MUC1/Y. The interaction of MUC1/Y with MUC1/SEC has important biological functional correlates: (a) it induces MUC1/Y phosphorylation; and (b) it has a pronounced effect on cell morphology. These findings suggest that MUC1/Y and MUC1/SEC form an active receptor/ cognate binding protein complex that can elicit cellular responses. The proteins comprising this complex are, thus, generated by alternative splicing from one and the same gene, namely the MUC1 gene.

Animals↗

Trigeminal neuralgia triggered by auditory stimuli in multiple sclerosis.

OBJECTIVES: To describe a patient with a demyelinating brainstem lesion who developed right-sided trigeminal neuralgia triggered by auditory stimuli and to discuss the pathophysiological mechanisms underlying this unusual phenomenon. DESIGN: Case report. SETTING: Referral center. PATIENT: A 27-year-old man who presented with clinical signs of a brainstem lesion developed right-sided trigeminal neuralgia triggered by auditory stimuli to the right ear. Magnetic resonance imaging and electrophysiological studies demonstrated a demyelinating lesion in the pons affecting the right lateral lemniscus and the right trigeminal pathway. This phenomenon completely subsided within 4 days. After a relapse, the diagnosis of clinically definite multiple sclerosis was made. CONCLUSION: Lateral spread of impulse activity within the demyelinating pontine lesion is the likely explanation for the unusual phenomenon of trigeminal neuralgia triggered by auditory stimuli.

Acoustic Stimulation↗

Blocking Na(+)-H+ exchange by cariporide reduces Na(+)-overload in ischemia and is cardioprotective.

In myocardial ischemia, rapid inactivation of Na(+)-K(+)-ATPase and continuing influx of sodium induce Na(+)-overload which is the basis of Ca(2+)-overload and irreversible tissue injury following reperfusion. The Na(+)-H(+)-exchanger of subtype 1 (NHE-1) is assumed to play a major role in this process, but previously available inhibitors were non-specific and did not allow to verify this hypothesis. Cariporide (HOE 642) is a recently synthesized NHE-1 inhibitor. We have investigated its effects on Na+ homeostasis (23Na NMR spectroscopy), cardiac function and energy metabolism (31P NMR) in ischemia and reperfusion. In the well-oxygenated, isolated guinea-pig heart, cariporide (10 microM) had no effect on intracellular Na+, pH or cardiac function. NHE-1 inhibition by cariporide was demonstrated using the NH4Cl prepulse technique. When hearts were subjected to 15 min of ischemia, cariporide markedly inhibited intracellular Na(+)-accumulation (1.3 +/- 0.1 vs 2.1 +/- 0.1-fold rise) but had no effect on the decline in pH. In reperfusion, NHE-1-blockade significantly delayed pH recovery. With longer periods of ischemia (36 min), cariporide delayed the onset of contracture, reduced ATP depletion, Na(+)-overload and again had no effect on pH. In reperfusion, hearts treated with cariporide showed an improved recovery of left ventricular pressure (60 +/- 1 vs 16 +/- 8 mmHg): end-diastolic pressure was normalized and phosphocreatine fully recovered, while there was only a partial recovery in controls. The data demonstrate that Na(+)-H(+)-exchange is an important port of Na(+)-entry in ischemia and contributes to H(+)-extrusion in reperfusion. By reducing Na(+)-overload in ischemia and prolonging acidosis in reperfusion, NHE-blockade represents a promising cardioprotective principle.

Adenosine Triphosphate↗

Endovascular therapy of arteriovenous fistulae with electrolytically detachable coils.

We report our experience in using Guglielmi electrolytically detachable coils (GDC) alone or in combination with other materials in the treatment of intracranial or cervical high-flow fistulae. We treated 14 patients with arteriovenous fistulae on brain-supplying vessels--three involving the external carotid or the vertebral artery, five the cavernous sinus and six the dural sinuses--by endovascular occlusion using electrolytically detachable platinum coils. The fistula was caused by trauma in six cases. In one case Ehlers-Danlos syndrome was the underlying disease, and in the remaining seven cases no aetiology could be found. Fistulae of the external carotid and vertebral arteries and caroticocavernous fistulae were reached via the transarterial route, while in all dural fistulae a combined transarterial-transvenous approach was chosen. All fistulae were treated using electrolytically detachable coils. While small fistulae could be occluded with electrolytically detachable coils alone, large fistulae were treated by using coils to build a stable basket for other types of coil or balloons. In 11 of the 14 patients, endovascular treatment resulted in complete occlusion of the fistula; in the remaining three occlusion was subtotal. Symptoms and signs were completely abolished by this treatment in 12 patients and reduced in 2. On clinical and neuroradiological follow-up (mean 16 months) no reappearance of symptoms was recorded.

Adult↗

Expression of interferon regulatory factors and indoleamine 2,3-dioxygenase in Chlamydia trachomatis-infected synovial fibroblasts.

Synovial fibroblasts probably represent host cells for Chlamydia trachomatis during initial intra-articular infection in reactive arthritis. In vitro synovial cells produce interferon-beta (IFN-beta) in response to chlamydial infection. IFN-beta expression can be activated by interferon regulatory factor-1 (IRF-1) and interferon-stimulated gene factor 3gamma (ISGF3gamma). In this study, we demonstrate that infection of synovial fibroblasts with C. trachomatis serotype D induced the expression of IRF-1 mRNA as shown by reverse transcription-PCR. Tumor necrosis factor-alpha (TNF-alpha) stimulation enhanced IRF-1 mRNA levels in infected cells and was required to detect IRF-1 protein by immunoblotting. The level of constitutively expressed IRF-2 was not significantly affected after infection. C. trachomatis was found to cause an up-regulation of ISGF3gamma protein in synovial cells. Induction of the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) is an important mechanism of the host cell response to control intracellular infection by chlamydiae. It has been described that IRF-1 can induce IDO gene expression. Infection of synovial fibroblasts alone in the absence of exogenous cytokine induced the expression of IDO mRNA which was enhanced by TNF-alpha treatment. The stimulation of IRF-1, ISGF3gamma, and IDO expression was most effective when viable chlamydiae were used as inoculum. Neutralization of IFN-beta in the culture medium of infected cells diminished but did not abrogate expression of IRF-1, ISGF3gamma, and IDO. The increased production of IRF-1 and ISGF3gamma in C. trachomatis-infected synovial fibroblasts may contribute to induction of IFN-beta and IDO.

Antibodies↗

Effects of pumaprazole (BY841), a novel reversible proton pump antagonist, and of omeprazole, on intragastric acidity before and after cure of Helicobacter pylori infection.

BACKGROUND: Omeprazole produces a higher intragastric pH in the presence of Helicobacter pylori infection than after cure. AIM: To investigate whether this effect also occurs with pumaprazole (BY841), a reversible proton pump antagonist which, in contrast to omeprazole, does not require activation in the acid compartment of the parietal cell. METHODS: In a randomized, crossover, double-blind study, 24-h intragastric pH was measured in 13 H. pylori-positive subjects before and after a 1-week course of omeprazole (20 mg o.d.) or of pumaprazole (100 mg b.d.). The studies were repeated after the infection was cured. RESULTS: In the absence of drug administration, the median 24-h pH values before cure (median 2.0, 90% CI: 1.2-3.2) did not differ from those after cure (median 1.5, 90% CI: 1.3-2.2; P = 0.115). The 24-h pH values were higher before cure of the infection than after during both pumaprazole (6.0, 4.8-6.7 vs. 4.3, 2.6-5.7; P = 0.002) and omeprazole (5.8, 4.0-6.2 vs. 3.6, 2.8-5; P = 0.004). Both before and after cure, there were no significant differences between the two drugs with respect to acid inhibition over the 24-h period. The median decrease in acid inhibition after cure of the infection (calculated as the difference in H+ activity in mmol/L) during pumaprazole (median 0.05, 90% CI: 6 x 10-4- 2.3) was no different from that during omeprazole (median 0.2, 90% CI: 3 x 10-3-1.5; P = 0.6). CONCLUSIONS: Both before and after cure of H. pylori infection, pumaprazole raised the intragastric pH over a 24-h period to a similar degree as omeprazole. H. pylori infection similarly augments the pH-increasing effect of both drugs. This effect is related to H. pylori infection and not to an increased activation of acid inhibitory agents in the parietal cell compartment.

Adult↗