Search PubMed⌕ Search

Biomedical subjects

D Müller

Publications and source records attributed to D Müller.

At least 127 records · Page 7Linked to original sources
PubMed1999

Clinical importance of prothrombotic risk factors in pediatric patients with malignancy--impact of central venous lines.

UNLABELLED: To evaluate the role of inherited thrombophilia in the development of central venous line (CVL)-related thrombosis, the following parameters were determined in 77 pediatric-oncologic patients with CVL: activated protein C (APC)-ratio, factor V (FV) G1691A and prothrombin G20210A mutation, protein C, protein S, antithrombin, coagulation factor XII, lipoprotein (a) and homocysteine. An inherited prothrombotic risk factor was found in 17 patients (23%). Four out of 14 patients with a single detect (hyperlipoproteinemia, heterozygous FV G1691A and prothrombin G20210A mutation, protein C deficiency type I) and all three patients with combined defects (heterozygous FV G1691A mutation combined with heterozygous prothrombin G20210A variant, protein S deficiency or hyperlipoproteinemia) suffered from CVL-related thrombosis. In 11 out of 77 patients (14%) a CVL-related thrombosis was detected. In 2 children thrombosis occurred a few days after asparaginase therapy and in another three thrombosis was associated with CVL-related septicemia caused by Staphylococcus epidermidis. After removal of CVL, thrombosis was detected in 5 children, in 2 without clinical symptoms but in the presence of inherited prothrombotic risk factors. CONCLUSION: The present study demonstrates the clinical importance of CVL in combination with inherited thrombophilia in the development of thrombosis in pediatric-oncologic patients. Before or shortly after insertion of CVL, patients should be tested for the presence of factor V G1691A mutation, prothrombin G20210A variant and increased lipoprotein (a) values.

Adolescent↗
PubMed1999

Proving the authenticity of ancient DNA by comparative genomic hybridization.

In PCR-supported amplification of ancient, degraded DNA, contamination with contemporary DNA can lead to false-positive results, which frequently give rise to discussions in which the mere existence of ancient DNA is doubted. Our confirmation of ancient DNA using comparative genome hybridization (CGH) eliminates these doubts. Unlike PCR methods, CGH requires no amplification of the DNA to be analyzed if adequate amounts of specimen DNA is used. Thus, false results traceable to contaminations are practically ruled out. The examples provided here prove the authenticity of ancient DNA for a 250-year-old and a 3,000-year-old sample. At the same time, the CGH of ancient DNA offers the chance to gain insight into the pattern of DNA degradation and to monitor the preservation of certain chromosomal segments.

Chromosomes, Human↗
PubMed1999

[Long-term efficacy of antitachycardia pacing for treatment of ventricular tachycardia in patients with implantable cardioverter/defibrillator].

UNLABELLED: Antitachycardia pacing techniques (ATP) have proved useful for termination of ventricular tachycardia (VT). However, little is known about the efficacy and safety off ATP during long-term follow-up in a larger study population. We analyzed the data of 80 ICD patients (pts) with spontaneous monormorphic VT, mean age 59 +/- 12 years, the mean follow-up was 26 +/- 17 months. 50 pts (62.5%) had coronary artery disease, 18 (22.5%) dilative cardiomyopathy (DCM), the remaining 12 pts (15%) had no or other cardiac diseases. 2926 episodes of ventricular tachycardia (cycle length 349 +/- 51 ms, 240-520 ms) occurred in 64/80 pts (80%), overall efficacy of ATP was 89.9%, acceleration occurred in 4.1% of VTs. Success of ATP did not correlate with positive ATP testing on induced arrhythmias, LVEF, NYHA class or aneurysm. Neither underlying heart disease nor antiarrhythmic medication had an impact on the ATP success rate. ATP efficacy was linked significantly to short VT cycle length (VTCL, 240-300 ms, p < 0.01) and long coupling intervals (91-97%), p < 0. 01). Acceleration occurred in 32% of pts and in 4.1% of VT episodes; it was also dependent on short VT cycle length (< 300 ms vs > 300 ms, p < 0.04) and short coupling intervals (< 81% vs >/= 81%, p </= 0. 01). CONCLUSIONS: First, ATP is a highly effective therapy, independent of patients characteristics. Second, short VT cycle length and long ATP coupling intervals were identified as predictors for successful ATP. Best conversation rates were obtained with coupling intervals between 90 and 97% of VTCL in tachycardias with a cycle length < 300 ms. Third, testing ATP on induced VTs before hospital discharge did not improve efficacy, empiric modes showed equal success rates. Fourth, acceleration rate of ATP depends on VT cycle length and coupling interval; therefore, aggressive ATP modes should be carefully applied in patients with VTs faster than 300 ms.

Adult↗
PubMed1999

Sertoli and Leydig cells of the human testis express neurofilament triplet proteins.

Using RT-PCR, western blot and enzyme and fluorescence immunocytochemical techniques, the three isoforms of neurofilament proteins (NFPs), namely NF-L (NFP-68 kDa), NF-M (NFP-160 kDa) and NF-H (NFP-200 kDa) were found in Sertoli and Leydig cells of human testes. RT-PCR showed specific for the three NFP fragments in testicular tissue, in isolated seminiferous tubules and in isolated Leydig cells. In protein preparations from the same testicular components, western blot analysis detected bands with molecular weights characteristic for NF-H, NF-M and NF-L. Application of immunofluorescence and immunoenzyme methods on cryostat and paraffin sections resulted in differences in the staining pattern in Sertoli cells and Leydig cells. In these cells, the NFPs showed predominantly a perinuclear location from which bundles emerge that were directed towards the basal, apical and lateral extensions of the Sertoli cells as well as the periphery of Leydig cells. NF-H coexists with vimentin-type filaments as seen by dual staining and staining of consecutive serial sections of material embedded in paraffin. In Sertoli cells, vimentin and NF-H showed distinct dynamic changes depending on the stage of spermatogenesis and some structural variations of seminiferous tubules. Although in some tubules both vimentin and NF-H immunoreactivity was present at high levels, in the Sertoli cells from most individuals an inverse relationship in the staining intensity of vimentin and NF-H was observed. The strongest NF-H immunoreactivity was detected in Sertoli cells associated with stage 3 spermatids, whereas vimentin immunoreactivity was most abundant in association with stage 5 spermatids. The leydig cells did not show functional changes of the NFP immunoreactivity. The results obtained provide new evidence for the heterogeneous phenotype of human Sertoli cells and raise the question of their exact nature and origin.

Aged↗
PubMed1999

Influence of hyperfiltration on the measurement of urinary N-acetyl-beta-D-glucosaminidase.

The measurement of urinary enzymes in patients with diabetes mellitus has become a useful additional test for the early detection of nephropathy. Controversy persists concerning methods of measurement since during early stages of insulin-dependent diabetes mellitus children develop the so-called hyperfiltration syndrome. This study was performed to determine whether elevated levels of excreted creatinine influence the determination of the enzyme N-acetyl-beta-D-glucosaminidase (NAG). Reference values for NAG in single-spot urines (units NAG/mmol creatinine) and in 24-h collections (units NAG/l urine) were established in two different groups of 105 and 111 healthy children. NAG was then measured in single-spot urines (as NAG/mmol creatinine) and in collection urines of 30 diabetic children within the same 24-h period and compared with the reference population. These results were compared with hemoglobin (Hb)A1(a-c) and fructosamine values as well as creatinine clearance of the diabetic patients. There was a direct correlation between the NAG levels in single-spot and 24-h urine collections of diabetic patients. However, the NAG/creatinine ratio in the single-spot urines did not correlate with the HbA1(a-c) or fructosamine level. When 24 h collections (expressed as NAG/l) were used, the results correlated well with HbA1(a-c) and fructosamine. There was an inverse correlation between the creatinine clearance and the NAG/creatinine ratio, i.e., a high creatinine clearance correlated with a low NAG/creatinine ratio. This was not the case for 24 h collections (expressed as units/l). Hence, in children with insulin-dependent diabetes mellitus 24-h urine collections should be used for urinanalysis. Parameters should not be related to creatinine, since the ratio of urinary protein and creatinine is unreliable because of the high urinary creatinine during the hyperfiltration state.

Acetylglucosaminidase↗
PubMed1999

Risk stratification following myocardial infarction in the thrombolytic era: a two-step strategy using noninvasive and invasive methods.

OBJECTIVES: We prospectively performed a two-step risk assessment in patients in the early phase after acute myocardial infarction (MI). BACKGROUND: Noninvasive methods like Holter electrocardiographic monitoring (HM) and determination of the left ventricular ejection fraction (EF) as well as the invasive technique of programmed ventricular stimulation (PVS) have been used to identify patients in the late phase after MI as candidates for prophylactic implantation of a cardioverter/defibrillator. However, it is unclear whether these results can be transferred to patients following acute MI. METHODS: A series of 657 patients with acute MI (< or = 75 years) underwent HM and EF. If one of the two methods yielded abnormal findings (HM > or = 20 ventricular ectopic beats/h/> or =10 ventricular pairs/day/ventricular tachycardia; EF < or = 40%), PVS was done (abnormal PVS: induction of monomorphic ventricular tachycardia, duration >10 s, cycle length > or = 230 ms). RESULTS: Of 657 patients, 304 (46%) had either an abnormal HM or EF. The PVS performed in 146 of 304 patients was abnormal in 22. During a mean follow-up of 37 months, there were 106 (16%) deaths, being sudden in 24 (3.6%), nonsudden cardiac in 45 (6.8%). The incidence of arrhythmic events (sudden cardiac death, symptomatic ventricular tachycardia, cardiac arrest) was 18% (4/22) with an abnormal PVS and only 4% (5/124) with a normal PVS (odds ratio 4.0, p=0.032). CONCLUSIONS: The rate of arrhythmic events is low in post-MI patients in the 1990s. Nevertheless, a two-step risk stratification is helpful in selecting candidates for a defibrillator trial aiming at primary prevention of sudden cardiac death after MI.

Combined Modality Therapy↗
PubMed1999

Influence of oestrogens on formation of reactive oxygen species in liver microsomes of differently aged male Wistar rats.

Metabolic pathways of oestrogens are the formation of catechol oestrogens (CE; 2- and 4-hydroxy-oestrogens), redox cycling of CE and free radical generation, mediated through cytochrome P450 (P450) oxidase/reductase activity. We checked the oestrogens oestradiol (E2), oestradiol valerate (E2V) and ethinyloestradiol (EE2) for formation of reactive oxygen species in vitro and ex vivo in male Wistar rats in dependence on age. In liver microsomes of 10-, 30-, 60- and 270-day-old rats the influence of E2, E2V and EE2 (10(-7)-10(-3) M) on NADPH-Fe(++)-stimulated lipid peroxidation (LPO), H2O2 generation and lucigenin (LUC) and luminol (LUM) amplified chemiluminescence (CL) was investigated. The same parameters, additionally P450 content and monooxygenase activities were measured in liver 9000 x g supernatants after subchronic administration of the oestrogens (1, 10 mg/kg b. wt. orally). The most important results are the strong inhibitory capacities of the oestrogens in vitro on LPO in the order of E2V < E2 < EE2, most pronounced in 10-, 60- and 270-day-old animals. In microsomes of 30-day-old rats with the highest control LPO the antioxidative effect of the oestrogens was lower. Whereas the H2O2 generation was not changed by E2, enhanced by E2V, but diminished by EE2 in all age groups, CL(LUC) and CL(LUM) were inhibited in the order of E2 < E2V < EE2. Also after subchronical treatment of the rats the antioxidative action of the oestrogens was evident, microsomal LPO was inhibited in the order of E2 < E2V < EE2. All oestrogens inhibited ethylmorphine N-demethylation. But enhanced H2O2 generation and increased CL(LUC) also indicate a formation of reactive oxygen species by these oestrogens. Obviously in vitro the antioxidative phenolic structure of the oestrogens dominates, whereas after in vivo administration the dose- and age-dependent biotransformation produces prooxidative in addition to antioxidative structures.

Aging↗
PubMed1999

Atomic force microscopy: a powerful tool to observe biomolecules at work.

Atomic force microscopes (AFMs) move a sharp tip attached to a soft cantilever in a TV-raster-like pattern over a surface and record deflections of the tip that correspond to the surface topography. When operated in physiological solutions, an AFM allows biomolecules to be observed in their native environment. Progress in instrumentation, sample-preparation methods and recording conditions has provided images of biomolecules and their assemblies that reveal submolecular details. In addition, the AFM allows conformational changes to be observed directly. This article discusses these points and illustrates them with some pertinent examples.

Microscopy, Atomic Force↗
PubMed1999

NMDA receptor characterization and subunit expression in rat cultured mesencephalic neurones.

1. NMDA-induced changes in free intracellular Ca2+ concentration ([Ca2+]i) were determined in individual cultured rat mesencephalic neurones by the fura-2 method. mRNA expression encoding NMDA receptor subunits (NR1, NR2A-D) was examined by RT-PCR. 2. NMDA (1-100 microM, plus 10 microM glycine) induced a concentration-dependent increase in [Ca2+]i (EC50 = 5.7 microM). The effect of NMDA was virtually insensitive to tetrodotoxin (0.3 microM) and nitrendipine (1 microM), but dependent on extracellular Ca2+. 5,7-Dichlorokynurenic acid (10 microM), a specific antagonist at the glycine binding site on the NMDA receptor, abolished the NMDA response. 3. Memantine, an open-channel blocker, and ifenprodil, a preferential non-competitive NR1/NR2B receptor antagonist diminished the NMDA effect with an IC50 value of 0.17 and 1 microM, respectively. Ethanol at 50 and 100 mM caused about 25 and 45%-inhibition, respectively. 4. Agarose gel analysis of the PCR products followed by ethidium bromide fluorescence or CSPD chemiluminescence detection revealed an almost exclusive expression of the NR1 splice variants lacking exon (E) 5 and E22. The 3' splice form without both E21 and E22 exceeded that containing E21 by approximately 4 fold. The relative amounts of NR2A, NR2B, NR2C corresponded to approximately 1:2:1. NR2D mRNA was also detectable. 5. In conclusion, mesencephalic neurones bear ethanol-sensitive NMDA receptors which might be involved in the development of ethanol dependence and withdrawal. The high affinity of NMDA to this receptor, its sensitivity to ifenprodil and memantine may suggest that the mesencephalic NMDA receptor comprises the NR1 splice variant lacking E5, NR2B, and NR2C, respectively.

2-Amino-5-phosphonovalerate↗
PubMed1999

Functional changes of ventricular late potentials by provocation with increase of heart rate. Evaluation during atrial pacing.

BACKGROUND: Standard methods fail to reveal late potentials in 20 to 30% of patients with ventricular arrhythmias after myocardial infarction. However, these patients may develop transient delayed ventricular activation during increases in heart rate. METHODS AND RESULTS: Atrial pacing was performed, at the rates of 100 min-1 and 120 min-1, in 50 patients after myocardial infarction. Twenty-six patients had a history of documented, sustained ventricular tachycardia, 12 had a history of ventricular fibrillation and 12 no history of ventricular arrhythmias. The low-noise surface electrocardiogram was analysed before and during atrial pacing in the time and frequency domains. Fifteen of 26 patients with ventricular tachycardia, four of 12 with ventricular fibrillation and three of 12 without ventricular arrhythmias experienced late potentials during sinus rhythm. Atrial pacing led to a shift of 26 +/- 15 ms of preexistent late potentials into the ST segment, this being greater in patients with anterior infarctions and to an increase in magnitude in patients with inferior infarctions. In patients without late potentials during sinus rhythm, atrial pacing provoked late potentials in eight of 11 patients with ventricular tachycardia, in four of eight patients with ventricular fibrillation and in one of nine patients without ventricular arrhythmias. Low amplitude signals (LAS) were increased in patients after inferior and filtered QRS in patients after anterior infarction. In 10 patients without cardiac disease no late potentials were detectable in the time and frequency domain either at rest or during increased heart rate. CONCLUSIONS: Increase in heart rate may unmask late potentials in patients prone to malignant ventricular arrhythmias. Therefore, functional late potential analysis with non-invasive clinical stress tests, i.e. exercise tests, should be performed only with an adequate rate response. This might identify patients at risk of malignant ventricular arrhythmias otherwise not identified with conventional late potential analysis.

Arrhythmias, Cardiac↗
PubMed1999

[Diagnostic imaging in hepatosplenic candidiasis].

Hepatosplenic candidiasis is a severe complication encountered in immuno-compromised patients. Different imaging techniques can establish the diagnosis. After an introduction to the pathophysiological and clinical principles, the role of plain radiography, radionuclide scans, ultrasound, computed tomography and magnetic resonance imaging is discussed.

Candidiasis↗
PubMed1999

Managing psychosocial adjustment to aphasia.

This article argues for incorporating psychosocial adjustment into treatment plans for people with aphasia. It proposes that rehabilitation is a social rather than a medical construct and that by adopting a broad range of intervention strategies, more effective approaches to reintegration can be adopted. Outcome measures relating to self-esteem are judged to be central to evaluating the efficacy of treatment. The role of social factors in managing psychosocial adjustment are considered alongside individual and family approaches to counseling. It is concluded that clinicians need to broaden their treatment program to include psychosocial adjustment in rehabilitation.

Adaptation, Psychological↗
PubMed1999

Point mutations throughout the GLI3 gene cause Greig cephalopolysyndactyly syndrome.

Greig cephalopolysyndactyly syndrome, characterized by craniofacial and limb anomalies (GCPS; MIM 175700), previously has been demonstrated to be associated with translocations as well as point mutations affecting one allele of the zinc finger gene GLI3. In addition to GCPS, Pallister-Hall syndrome (PHS; MIM 146510) and post-axial polydactyly type A (PAP-A; MIM 174200), two other disorders of human development, are caused by GLI3 mutations. In order to gain more insight into the mutational spectrum associated with a single phenotype, we report here the extension of the GLI3 mutation analysis to 24 new GCPS cases. We report the identification of 15 novel mutations present in one of the patient's GLI3 alleles. The mutations map throughout the coding gene regions. The majority are truncating mutations (nine of 15) that engender prematurely terminated protein products mostly but not exclusively N-terminally to or within the central region encoding the DNA-binding domain. Two missense and two splicing mutations mapping within the zinc finger motifs presumably also interfere with DNA binding. The five mutations identified within the protein regions C-terminal to the zinc fingers putatively affect additional functional properties of GLI3. In cell transfection experiments using fusions of the DNA-binding domain of yeast GAL4 to different segments of GLI3, transactivating capacity was assigned to two adjacent independent domains (TA(1)and TA(2)) in the C-terminal third of GLI3. Since these are the only functional domains affected by three C-terminally truncating mutations, we postulate that GCPS may be due either to haploinsufficiency resulting from the complete loss of one gene copy or to functional haploinsufficiency related to compromised properties of this transcription factor such as DNA binding and transactivation.

Animals↗
PubMed1999

Regulation of arginine vasopressin in enuretic children under fluid restriction.

BACKGROUND: Treatment of primary nocturnal enuresis using 1-deamino-8-D-arginine-vasopressin is based on the hypothesis that antidiuretic hormone (arginine vasopressin [AVP]) secretion is insufficient during the night. Persisting doubts about the theoretical background of this treatment and first results pointing to a different AVP regulation in children with nocturnal enuresis were the motives for the present study. OBJECTIVE: To determine if children with primary nocturnal enuresis have different AVP levels during fluid restriction when compared with normal controls. METHODS: Twenty-three children with nocturnal enuresis (median age, 11 years) were compared with a corresponding control group of 18 healthy children. Plasma osmolality, urine osmolality, and plasma AVP concentrations were determined before and after a defined fluid restriction. RESULTS: Regarding plasma and urine osmolality, no differences were found between the two groups. AVP levels after fluid restriction, however, showed significant differences. To maintain osmolality, the plasma AVP concentrations of the controls rose to a median value of 5.7 pg/mL (range: 0.9-29.0 pg/mL) in comparison to a median of 14.0 pg/mL (range: 3.5-64.0 pg/mL, P =. 015) for the enuretic children. CONCLUSION: The results are consistent with the established fact that AVP secretion is a function of plasma osmolality. They contradict the hypothesis that enuretic children have a AVP deficiency that has to be supplemented. Rather, the results point to a defect at the AVP receptor level or of the signal transduction pathway.

Adolescent↗
PubMed1998

[The Advanced Breast Biopsy Instrumentation (ABBI), a system for stereotactic excision of mammographically suspect nonpalpable findings in the breast].

Advanced Breast Biopsy Instrumentation (ABBI) allows radiologically guided stereotactic excision of non-palpable radiodense lesions with high accuracy. Tissue cylinders of 5, 10, 15 or 20 mm diameter and of variable lengths can be removed very accurately under local anaesthesia and on an outpatient basis. Thirty-six patients with suspicious clusters of microcalcifications (n = 29) and with round lesions (n = 7) of the breast were qualified for ABBI. We were able to perform the excisional biopsy in a total of 34 patients. The breast of one woman was too small to safely fit into the system and in another woman the lesion could not be visualized by the system. In 2/34 cases (6%), the excision was imprecise due to slight dislocation of the breast parenchyma by the advancing cylinder knife. In one case (3%), ABBI missed the target within a dense mastopathic breast. In all cases the excisions were well tolerated. No wound complications occurred and the cosmetic result was excellent. Histology revealed 28 benign (82%) and 6 malignant (18%) lesions. Among the 27 small microcalcifications there were 3 invasive carcinomas, 3 ductal carcinomas in situ (DCIS), 1 lobular hyperplasia, 14 mastopathies, 1 fibroadenoma, 1 duct papilloma and 4 calcifications in scars. Four of the 7 round-shaped lesions were found to be fibroadenomas, 1 lobular hyperplasia, and 2 mastopathies. With the ABBI system, non-palpable breast lesions can be precisely localized and excised.

Adult↗