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Biomedical subjects

M Pietsch

Publications and source records attributed to M Pietsch.

At least 37 records · Page 2Linked to original sources
PubMed2000

Volatile constituents of wood-rotting basidiomycetes.

Phytochemical investigation of the hydrodistillation products of the basidiomycetes Fomitopsis pinicola, Piptoporus betulinus, Gloeophyllum odoratum and Trametes suaveolens led to the identification of numerous mono- and sesquiterpenes as well as many aliphatic alcohols, aldehydes and ketones and some aromatic compounds. In addition, some diterpenes were identified as constituents of Fomitopsis pinicola. The absolute configuration of some terpenes was determined

Basidiomycota↗
PubMed2000

Behavioural and emotional problems in early-treated adolescents with phenylketonuria in comparison with diabetic patients and healthy controls.

Even early-treated patients with phenylketonuria (PKU) have a higher risk of psychosocial maladjustment. This study was performed to determine whether emotional and behavioural problems are specific in phenylketonurics and whether they depend on the quality of biochemical control. This comparative study covered 42 PKU patients aged 10-18 years (mean 14.7 years) and 42 diabetic patients matched for sex, age and socioeconomic status. Patients' groups were compared with a control sample of healthy controls (n = 2900) from an epidemiological study. We used the Child Behavior Check List (CBCL) according to Achenbach, intelligence quotient (IQ) test according to Weiss, and monitoring of blood phenylalanine concentrations and HBA1 concentrations. Internalizing problems such as depressive mood, anxiety, physical complaints or social isolation were significantly elevated in both phenylketonuric and diabetic patients, whereas externalizing problems were not. The two patient groups did not differ significantly either in the degree or in the pattern of their psychological profile. In both groups no significant correlations could be computed between the psychological characteristics and the biochemical control, the IQ, and the socioeconomic status. No patient was undergoing psychiatric treatment or psychotherapy. Our results strongly support a psychological perspective for the development of behavioural and emotional problems in both phenylketonuric and diabetic patients. Thus, medical treatment should be accompanied by psychological support for the families.

Adolescent↗
PubMed2000

Crataegus special extract WS 1442 increases force of contraction in human myocardium cAMP-independently.

The mode of action of Crataegus extracts in the treatment of heart failure is still under examination. WS 1442, a standardized special extract from Crataegus leaves with flowers, exerts direct positive inotropic effects. This study was designed to investigate the mode of inotropic action of WS 1442 in human myocardium from patients with congestive heart failure (left ventricular myocardium from explanted hearts; NYHA IV, n = 8) as well as in nonfailing controls (right auricular trabeculae from patients with coronary heart disease, n = 8). WS 1442 effectively displaced specifically bound 3H-ouabain but did not influence the activity of adenylate cyclase [control, + Gpp(NH)p (10(-4) microM) 3,500 pmol cyclic adenosine monophosphate (cAMP)/20 min). In isolated left ventricular papillary muscle strips, WS 1442 significantly increased the force of contraction [basal, 1.8+/-0.2 mN; WS 1442 (50 microg/ml), 2.4+/-0.1 mN (130%)] and improved the frequency-dependent force generation (0.5 vs. 2.5 Hz: control, +0.1+/-0.01 mN; WS 1442, +0.9+/-0.3 mN) even in failing human myocardium. In fura-2-loaded muscle strips (right atrial trabeculae), WS 1442 increased both the Ca2+-transient and force generation. These effects also were observed in the lipophilic ethyl acetate-soluble fraction A, enriched in flavone derivatives. In conclusion, these findings suggest a pharmacologic mechanism of WS 1442 similar to the cAMP-independent positive inotropic action of cardiac glycosides. In addition, WS 1442 improves the force-frequency relation in failing human myocardium.

Adenylyl Cyclases↗
PubMed1999

2-(diethylamino)thieno1,3ŏxazin-4-ones as stable inhibitors of human leukocyte elastase.

A series of 2-(diethylamino)thieno1,3ŏxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase (HLE). The Gewald thiophene synthesis was utilized to obtain several ethyl 2-aminothiophene-3-carboxylates. These precursors were subjected to a five-step route to obtain thieno2,3-d1,3ŏxazin-4-ones bearing various substituents at positions 5 and 6. Both thieno2,3-d and thieno3,2-d fused oxazin-4-ones possess extraordinary chemical stability, which was expressed as rate constants of the alkaline hydrolysis. The kinetic parameters of the HLE inhibition were determined. The most potent compound, 2-(diethylamino)-4H-1benzothieno2,3-d1,3ŏxazin-4-one, exhibited a K(i) value of 5.8 nM. 2-(Diethylamino)thieno1, 3ŏxazin-4-ones act as acyl-enzyme inhibitors of HLE, similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. The isosteric benzene-thiophene replacement accounts for an enhanced stability of the acyl-enzyme intermediates.

Enzyme Inhibitors↗
PubMed1999

The intracellular Ca(2+)-homeostasis influences the frequency-dependent force-generation in man.

The present study investigates the effect of stimulation frequency and external Ca(2+)-concentration on intracellular systolic and diastolic Ca2+ as well as on the force-frequency relationship (FFR, 0.5 to 3.0 Hz, 1.0 mmol/l extracellular Ca2+) in human myocardium using fura-2 AM loaded electrically stimulated right atrial muscle strips (coronary bypass surgery, n = 15, age: 60.0 +/- 1.9 years). The FFR was positive (3.0 vs. 0.5 Hz: 184 +/- 43% of basal value) and linked to an increase in peak systolic (R340/380sys, 119 +/- 7%) as well as diastolic Ca2+ (R340/380ED, delta fura-2 ratio +0.20 +/- 0.02). After elevating the extracellular Ca2+ concentration from 1.0 to 2.4 mmol/l, force of contraction (FOC) increased from 0.5 up to 1.0 Hz (128 +/- 8%) and declined after further augmentation of stimulation frequency (3.0 Hz: 87 +/- 15%). However, this decrease in FOC was accompanied by an increase in diastolic Ca2+ (delta fura-2 ratio +0.45 +/- 0.08), while systolic Ca2+ declined at high stimulation frequencies. In conclusion, the frequency-dependent force generation is accompanied by an increase in both systolic and diastolic Ca2+ levels. Thus, especially at high stimulation frequencies the Ca(2+)-lowering mechanisms may become crucial and may be responsible for the blunted force-frequency relationship in failing human myocardium.

Aged↗
PubMed1999

Regression of neuropsychological deficits in early-treated phenylketonurics during adolescence.

Even early-treated phenylketonuric patients suffer from phenylalanine-associated (mild) neuropsychological impairment. To date it is still unclear whether patients' deficits show a progression on ageing. This unsolved question seems to be an important aspect in the still ongoing debate about how long and how strictly the patients should be maintained on diet. Twenty early-treated (20 +/- 10, 9-30 days) adolescent phenylketonurics (10 boys, 10 girls) and 20 healthy controls, matched for age, sex and IQ, were investigated twice at a mean ages of 11 and 14 years for their IQ (Culture Fair Intelligence Test-Scale 2; CFT-20), fine motor abilities (Motor Performance Task), sustained (Test d2) and selective attention (Stroop-Task). At the first test, examinations revealed significant blood phenylalanine-correlated neuropsychological deficits in PKU patients. In spite of raised blood phenylalanine concentrations during the following 3 years and significantly elevated concurrent blood phenylalanine concentrations, the repeated measurements revealed a significant decrease of patients' deficits compared to controls. Clinical-neurological status of patients and controls was normal at both test times. The results indicate a decreased vulnerability of PKU-patients with respect to their neuropsychological functioning against elevated blood phenylalanine levels on ageing.

Adolescent↗
PubMed1998

Unchanged sarcoplasmic reticulum Ca2+-ATPase activity, reduced Ca2+ sensitivity, and negative force-frequency relationship in transgenic rats overexpressing the mouse renin gene.

Transgenic rats overexpressing the mouse Ren-2 gene [TG(mREN2)27 rats, TGR] were used to characterize alterations in force generation and relaxation following cardiac hypertrophy. Age-matched Sprague-Dawley rats were used as the control group. The beta-adrenoceptor dependent increase in force of contraction was reduced in the transgenic animals but not the Ca2+-dependent increase in force generation. Additionally, force of contraction decreased after increasing stimulation frequencies (up to 7 Hz), but the frequency-dependent decrease in force of contraction was significantly more pronounced in the transgenic group. The Ca2+ sensitivity in chemically skinned fiber preparations of TGR was reduced than that in Sprague-Dawley rats while maximum effectiveness was the same. Unexpectedly, the sarcoplasmic reticulum Ca2+-ATPase activity measured in crude membrane preparations from TGR did not differ from that in Sprague-Dawley rats; however, the activity of the Na+/K+-ATPase was less while the Na+/Ca2+-exchanger activity was significantly greater. In the same preparations the protein expression of SERCA2 was reduced in TGR while expression of phospholamban and calsequestrin remained the same. Thus in the model of cardiac hypertrophy harboring the mouse Ren-2 gene the hypothesized correlation between SERCA2 function and force-frequency relationship was not observed. Possible reasons for the more negative force-frequency relationship in TGR included changes at the level of the myofilaments and altered intracellular Na+ homeostasis which may result from the reciprocal changes in the Na+/K+-ATPase and the Na+/Ca2+-exchanger activity.

Animals↗
PubMed1998

Auxiliary liver transplantation with arterialization of the portal vein for acute hepatic failure.

Six adult patients suffering from acute hepatic failure and with a high urgent status underwent heterotopic auxiliary liver transplantation. In four of these patients, the portal vein of the liver graft was arterialized in order to leave the native liver and the liver hilum untouched and to be able to place the liver graft wherever space was available in the abdomen. The arterial blood flow via the portal vein was tapered by the width of the anastomosis. Two patients died, one of sepsis on postoperative day 17 (POD), the other after 3 months due to a severe CMV pneumonia. There were no technically related deaths. The native liver showed early regeneration in all cases. In one patient, the auxiliary graft was removed 6 weeks after transplantation. Four weeks later, he had to undergo orthotopic retransplantation due to a recurrent fulminant failure of the recovered native liver. This patient is alive more than 1 year after the operation. We conclude that heterotopic auxiliary liver transplantation with portal vein arterialization is a suitable approach to bridging the recovery of the acute failing native liver.

Acute Disease↗
PubMed1998

Implantable vascular access systems: experience in 1500 patients with totally implanted central venous port systems.

Totally implantable venous access systems are widely used, but large-scale studies evaluating these systems are lacking. In this study 1500 patients (719 male, 781 female) with an average age of 49 years (15-86 years) were fitted with subcutaneously implanted venous access systems, in most cases for long-term chemotherapy. All patients were observed until removal of the system, death, or the end of treatment. A retrospective analysis showed an average catheter life of 284 patient-days. A total of 1308 (87%) of the patients had no implant-related complications. Catheter infections occurred in 3.2% of the patients and catheter thromboses in 2.5%. Rarer complications, such as catheter malfunction, migration of the catheter, skin necrosis, catheter fracture, catheter disconnection, and pneumothorax, occurred in another 4.3% of the patients. The complications led to explantation of 178 access systems (11.9%). There was a significant difference (p < 0.05) between the low rate of infections and other complications in the group of patients with solid tumors (2% and 4%, respectively) and the rate in patients with hematologic diseases (6% and 8%, respectively). This study confirms the safety and convenience of using totally implantable venous access systems in patients on long-term chemotherapy.

Adolescent↗
PubMed1998

Immunologic findings in workers formerly exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin and its congeners.

One hundred ninety-two workers in a German pesticide factory who were exposed to polychlorinated dibenzodioxins and -furans (PCDD/PCDF) were investigated for former and present diseases and laboratory changes of the immune system. Moreover, in a subgroup of 29 highly exposed and 28 control persons, proliferation studies were performed. In addition to assays such as blood count, immunoglobulins, serum electrophoresis, monoclonal bands, surface markers, autoantibodies, and lymphocyte proliferation, two new methods, the rise of tetanus antibody concentration after vaccination and the in vitro resistance of lymphocytes to chromate, were used to diagnose the morphologic and functional state of the immune system. There was no stringent correlation of actual PCDD/PCDF concentrations with the occurrence of infections or with one of the immune parameters. In addition, outcomes of the tetanus vaccination and the chromate resistance test were not correlated with PCDD/PCDF. However, the chromate resistance of lymphocytes stimulated by phytohemagglutinin of highly exposed persons was significantly lower than that for the control group. These findings indicate that the function of lymphocytes can be stressed and possibly impaired by high exposure to PCDD/PCDF.

Adult↗
PubMed1997

[Treatment and follow-up of patients with squamous epithelial carcinoma of the penis].

Since squamous cell carcinoma of the penis is rare, prospective trials do not exist. Therefore, new treatment strategies have to be developed. Based on our experience with the treatment of 22 patients with penile squamous cell carcinoma, we describe our therapeutic approaches. Ten patients with superficial disease (T1-2N0M0) were treated with partial penectomy. The 3-year survival rate amounted to 90%. In patients with extensive disease (T3-4 or N1-3) a partial or total penectomy was performed. After initial antibiotic therapy for 4 weeks, patients underwent inguinal lymph-node dissection and if the nodes were positive, additional pelvic lymph-node dissection. In patients with ulcerous inguinal lymph-node metastases surgical resection was performed, covering the wound with a musculocutaneous flap (tensor fascia lata flap n = 2; rectus abdominis flap n = 1). The 3-year survival rate of patients with T1-2N1 tumours (n = 4) was 67% and with T3-4N1-3 (n = 8) 25%. Patients with distant metastases received inductive systemic chemotherapy with cisplatin, methotrexate and bleomycin. Objective responses occurred in 22% (1 CR, 1 PR) of 9 patients. These results suggest that immediate radical surgery with lymph-node dissection is the best treatment for squamous cell carcinoma of the penis.

Adult↗
PubMed1997

Progression of cerebral white matter abnormalities in early treated patients with phenylketonuria during adolescence.

In this study of cranial MRI a group of 15 adolescents with classical phenylketonuria and permanent blood phenylalanine (phe) checks from infancy was investigated twice with an interval of three years in between. Cranial MRI revealed a progression of white matter abnormalities in patients with moderate and poor control of blood phe levels, however not in well controlled patients. Nevertheless results indicate an individual vulnerability of the brain against elevated phenylalanine levels in phenylketonurics.

Adolescent↗
PubMed1997

Neuropsychological, intellectual, and behavioral findings in patients with centrotemporal spikes with and without seizures.

Forty children (23 boys, 17 girls) with centrotemporal spikes (rolandic focus) with and without seizures (mean age 8.4 years +/- 4.8 SD), and 40 healthy controls matched for age, sex, and socioeconomic status were assessed for their neuropsychological, intellectual, and behavioral outcome. Compared with the controls, patients were significantly impaired in their IQ, visual perception, short-term memory, in their psychiatric status and in some subtests in a fine motor performance task. No significant differences could be computed for a simple finger-motor speed exercise or a linguistic performance test. In patients, deficits in IQ were significantly correlated with frequency of spikes in the EEG, but not with frequency of seizures, lateralization of the rolandic focus, or time since rolandic focus was diagnosed. It was concluded that a rolandic focus is not as benign as once thought.

Analysis of Variance↗
PubMed1997

Effect of inotropic interventions on contraction and Ca2+ transients in the human heart.

The present study investigated the influences of inotropic intervention on the intracellular Ca2+ transient (intracellular Ca2+ concentration ([Ca2+]i)) and contractile twitch. Isometric twitch and [Ca2+]i (fura 2 ratio method) were measured simultaneously (1 Hz, 37 degrees C) after stimulation with Ca2+ (0.9-3.2 mM), the cardiac glycoside ouabain (Oua; 0.1 microM), the beta1- and beta2-adrenoceptor-agonist isoprenaline (Iso; 1-10 nM), and the Ca2+ sensitizer EMD-57033 (30 microM) by using isolated human nonfailing right auricular trabeculae (n = 19). Inotropic interventions increased force of contraction and peak rate of tension rise (+T) significantly. Only Iso stimulated peak rate of tension decay (-T) higher than +T (P < 0.05), thereby reducing time of contraction (Ttwitch). EMD-57033 increased +T more effectively than -T and prolonged Ttwitch (P < 0.05). Ca2+, Oua, and Iso, but not EMD-57033, increased systolic Ca2+. Diastolic Ca2+ increased after stimulation with Oua or Ca2+, but not in the presence of EMD-57033. Iso shortened the Ca2+ transient and did not influence diastolic Ca2+. In conclusion, positive inotropic agents differently affect force and [Ca2+]i depending on their mode of action. Inotropic interventions influence diastolic Ca2+ and thus may be less advantageous in a situation with altered intracellular Ca2+ homeostasis (e.g., heart failure due to dilated cardiomyopathy).

Adult↗
PubMed1997

Intellectual, neurologic, and neuropsychologic outcome in untreated subjects with nonphenylketonuria hyperphenylalaninemia. German Collaborative Study on Phenylketonuria.

Based on the serum phenylalanine levels under free diet patients with hyperphenylalaninemia are classified as "classical" (>1200 micromol/L), "mild" (600-1200 micromol/L), or "non-phenylketonuria (PKU)-hyperphenylalaninemia" (<600 micromol/L). Recent studies revealed intellectual, neurologic, and neuropsychologic deficits as well as abnormalities of cerebral white matter (magnetic resonance imaging, MRI) in patients with early and adequately treated PKU. In addition deficits in IQ were reported for a group of 4-y-old patients with untreated mild PKU and non-PKU hyperphenylalaninemia (serum phenylalanine levels below 900 micromol/L). As a consequence, a lifelong diet with serum phenylalanine levels below 400 micromol/L was recommended even for those patients with serum phenylalanine levels remaining consistently between 400 and 600 micromol/L. Generally patients with non-PKU hyperphenylalaninemia were not treated, as a normal outcome was suspected, but the clinical development of patients with non-PKU hyperphenylalaninemia was not so far studied systematically. We assessed 28 untreated patients with non-PKU hyperphenylalaninemia (age: mean = 21.8, SD = 4.2 y) for IQ, school and job career, clinical-neurologic development, fine motor performances, selective and sustained attention, as well as for frontal lobe-dependent "executive functions." In addition, cranial MRI was obtained in 10 of these patients. Compared with healthy control subjects, matched for age, sex, and socioeconomic status, the patients reached normal results in all clinical and psychometric tests. Cranial MRI revealed no abnormalities. Additionally, no significant correlations between serum phenylalanine levels and test results were obtained. In the absence of any demonstrative effect, treatment is unlikely to be of significant effect in patients with non-PKU hyperphenylalaninemia.

Adolescent↗