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Biomedical subjects

G Lehmann

Publications and source records attributed to G Lehmann.

At least 37 records · Page 2Linked to original sources

Real-time quantitative PCR of telomerase mRNA is useful for the differentiation of benign and malignant pancreatic disorders.

The presence of telomerase activity has been proposed as a specific and sensitive marker for malignant tissue, and positivity rates of up to 95% have been reported in pancreatic cancer. In the present study telomerase activity analysis was reevaluated in 29 pancreatic cancer tissues compared with 36 chronic pancreatitis tissues and 21 normal controls, and a study was made of whether malignant and benign pancreatic disorders can be better differentiated using a novel technique real-time quantitative PCR analysis-analyzing telomerase mRNA expression. Telomerase activity was present in 35% (10 of 29) of pancreatic cancer samples, 3% (one of 36) of chronic pancreatitis samples, and none of the normal pancreatic tissue samples in the TRAP assay. Real-time quantitative PCR analysis revealed the presence of telomerase mRNA expression in 50% (10 of 20) of normal, 86% (31 of 36) of chronic pancreatitis, and 90% (26 of 29) of pancreatic cancer samples. However, quantification of the expression data revealed that the relative increase above normal was 5.5 (range, 3.5-8.6) for chronic pancreatitis and 23.9 (range, 18.6-30.7) for pancreatic cancer samples (p < 0.01). No relationship was found between telomerase activity and the fold increase of telomerase mRNA above normal and gender, patient age, tumor stage, or tumor grade. These data indicate that detection of telomerase activity using the TRAP assay has limitations in differentiating benign and malignant pancreatic disorders. However, telomerase mRNA analysis by real-time quantitative PCR analysis allows a highly sensitive detection and differentiation of pancreatic cancer from normal pancreas and chronic pancreatitis and thereby may serve as a new reliable, easy, and effective diagnostic tool for cancer diagnosis.

Adult↗

Diagnosis of acute myocardial infarction in angiographically documented occluded infarct vessel : limitations of ST-segment elevation in standard and extended ECG leads.

STUDY OBJECTIVES: The majority of thrombolysis studies require defined ST-segment elevations as an inclusion criterion for the diagnosis of acute myocardial infarction (AMI). However, depending on the occluded infarct vessel and the criteria applied, the ECG diagnosis of AMI can be difficult to establish. Accordingly, this study was performed to evaluate the sensitivity of ST-segment elevation of standard and extended ECG leads in a cohort of patients with angiographically confirmed diagnosis of AMI. PATIENTS AND METHODS: In 418 patients (mean +/- SD age, 60 +/- 13 years) with AMI (pain onset, 4.8 +/- 3.0 h), coronary angiography with percutaneous transluminal coronary angioplasty/stenting of the culprit lesion was performed. The diagnosis of AMI was confirmed by emergency coronary angiography and laboratory analyses. ST-segment elevation (in two contiguous leads) of 1 mm in standard lead I through aVF and ST-segment elevations of 2 mm (or 1 mm, corresponding values presented in parentheses) in V(1) through V(6) were considered significant. In a subset of 102 AMI patients, additional right precordial leads V(3)R through V(6)R for evaluation of right ventricular infarction and additional chest leads V(7) through V(9) for evaluation of posterior infarction were recorded. ST-segment elevations of 1 mm in the right precordial leads and 1 mm or 0.5 mm in the posterior leads were considered significant. RESULTS: Standard leads I through V(6) showed ST-segment elevation in 85% (96%) of patients with left anterior descending artery occlusion, in 46% (61%) of patients with left circumflex coronary artery (CX) occlusion, and in 85% (90%) of patients with right coronary artery occlusion. On consideration of additional ECG tracings in the subgroup of 102 patients (V(3)R through V(6)R and V(7) through V(9)), the respective numbers increased by 2 to 8% depending on different criteria for ST-segment elevation; in patients with CX occlusion, the increase amounted to 6 to 14%. There was a trend toward an extended infarct size (maximum creatine kinase [CK] values) with concomitant ST-segment elevation in additional ECG leads as assessed by maximum CK levels. CONCLUSIONS: The sensitivity of the ECG diagnosis of AMI is only marginally increased by extended precordial chest leads. There is a trend toward an extended infarct size in those patients with concomitant ST-segment elevation in additional ECG leads.

Angioplasty, Balloon, Coronary↗

Vertebral metastases from pineoblastoma.

Two male patients aged 26 and 18 years presented with vertebral metastases originating from pineoblastomas on which surgery had been performed 8 years and 5 months earlier, respectively. In the first case in which the metastasis developed in the T8 corpus, the disease is presently under control after high-dose chemotherapy and autologous blood stem cell transplantation. The second patient (sacral metastasis), despite aggressive adjuvant therapy, died 2 years after the last operation because of spinal seeding. These uncommon cases are discussed with reference to the literature on extraneural metastases that originate from neuroepithelial tumors of the central nervous system.

Adolescent↗

STRING: a web-server to retrieve and display the repeatedly occurring neighbourhood of a gene.

The repeated occurrence of genes in each other's neighbourhood on genomes has been shown to indicate a functional association between the proteins they encode. Here we introduce STRING (search tool for recurring instances of neighbouring genes), a tool to retrieve and display the genes a query gene repeatedly occurs with in clusters on the genome. The tool performs iterative searches and visualises the results in their genomic context. By finding the genomically associated genes for a query, it delineates a set of potentially functionally associated genes. The usefulness of STRING is illustrated with an example that suggests a functional context for an RNA methylase with unknown specificity.

Genes, Bacterial↗

EST comparison indicates 38% of human mRNAs contain possible alternative splice forms.

Expressed sequence tag (EST) databases represent a large volume of information on expressed genes including tissue type, expression profile and exon structure. In this study we create an extensive data set of human alternative splicing. We report the analysis of 7867 non-redundant mRNAs, 3011 of which contained alternative splice forms (38% of all mRNAs analysed). From a total of 12572 ESTs 4560 different possible alternative splice forms were detected. Interestingly, 70% of the alternative splice forms correspond to exon deletion events with only 30% exonic insertions. We experimentally verified 19 different splice forms from 16 genes in a total subset of 20 studied; all of the respective genes are of medical relevance.

Alternative Splicing↗

ECG changes in a 25-year-old woman with hypocalcemia due to hypoparathyroidism. Hypocalcemia mimicking acute myocardial infarction.

The case of a 25-year-old woman presenting with chest pain, ECG changes, and laboratory findings suggestive of myocardial infarction is reported. Cardiac catheterization showed impaired left ventricular performance but otherwise normal coronary arteries. Laboratory analyses revealed primary hypoparathyroidism, and supplementation with calcium and vitamin D(3) was initiated. There was subsequent improvement in laboratory findings as well as echocardiographically determined left ventricular performance. Thereafter, the patient remained asymptomatic. Apart from some persisting ECG repolarization disturbances, there was complete normalization of the initial changes. This case demonstrates a combination of clinical, blood biochemical, and ECG findings mimicking acute myocardial infarction.

Adult↗

Recurrent symptomatic bilateral bundle branch block in a 74-year-old patient with a prosthetic aortic valve: a description of a case and review of the literature.

This report concerns a 74-year-old patient who had undergone aortic valve replacement 11 years earlier. On admission, the patient complained of shortness of breath when climbing two flights of stairs; there was no history of dizziness, fainting or sensations of arrhythmias. An ECG at rest showed first-degree atrioventricular (A-V) block together with left bundle branch block (LBBB). On bicycle ergometry, there was a fall in blood pressure and in heart rate due to a second-degree (2:1) A-V block along with the LBBB. After termination of exercise, the PR interval increased further from 0.24 s to >0.3 s, together with right bundle branch block (RBBB) and 1:1 A-V conduction instead of LBBB. Finally, at a constant atrial rate of 98/min, the RBBB disappeared, LBBB recurred, again with 2:1 A-V conduction. The diagnosis was bilateral BBB together with first degree A-V block at rest and higher-degree A-V block on effort. The patient underwent pacemaker implantation and was discharged shortly thereafter free of symptoms.

Aged↗

Marked reduction in atrial defibrillation thresholds with repeated internal cardioversion.

OBJECTIVES: This study was performed to assess the atrial defibrillation threshold in patients with recurrent atrial fibrillation (AF) using repeated internal cardioversion. BACKGROUND: Previous studies in patients with chronic AF undergoing internal cardioversion have shown this method to be effective and safe. However, current energy requirements might preclude patients with longer-lasting AF from being eligible for an implantable atrial defibrillator. METHODS: Internal shocks were delivered via defibrillation electrodes placed in the right atrium (cathode) and the coronary sinus (anode) or the right atrium (cathode) and the left pulmonary artery. After cardioversion, patients were orally treated with sotalol (mean 189 +/- 63 mg/day). Eighty consecutive patients with chronic AF (mean duration 291 +/- 237 days) underwent internal cardioversion, and sinus rhythm was restored in 74 patients. Eighteen patients underwent repeated internal cardioversion using the same electrode position and shock configuration after recurrence of AF (mean duration 34 +/- 25 days). RESULTS: In these 18 patients, the overall mean defibrillation threshold was 6.67 +/- 3.09 J for the first cardioversion and 3.83 +/- 2.62 J for the second (p = 0.003). Mean lead impedance was 55.6 +/- 5.1 ohms and 57.1 +/- 3.7 ohms, respectively (not significant). For sedation, 6.7 +/- 2.9 mg and 3.9 +/- 2.2 mg midazolam were administered intravenously (p = 0.003), and the pain score (0 = not felt, 10 = intolerable) was 5.1 +/- 1.9 and 2.7 +/- 1.8 (p = 0.001). Uni- and multivariate analyses revealed only the duration of AF before cardioversion to be of relevance, lasting 175 +/- 113 days before the first and 34 +/- 25 days before the second cardioversion in these 18 patients (p = 0.002). CONCLUSIONS: If the duration of AF is reduced, a significant reduction in defibrillation energy requirements for internal cardioversion ensues. This might extend the group of patients eligible for an implantable atrial defibrillator despite relatively high initial defibrillation thresholds.

Adult↗

Investigations of bone turnover in renal osteopathy.

The renal bone disease which develops in chronic renal failure (CRF) is not an uniform disorder. Histomorphometry is accepted to be the best method for characterising the state of disease. The purpose of this study was to evaluate the suitability of pyridinium crosslinks in serum and urine as indicators of bone degradation processes. Patients with CRF had significantly higher Pyridinoline (Pyd) and Deoxypyridinoline (Dpyd) levels in serum and urine compared to normal controls except the urinary excretion in the subgroup of glomerulonephritis. A correlation was found between the serum levels of crosslinks and those of both creatinine and parathormone. The Pyd and Dpyd serum levels in patients under dialysis treatment were significantly higher than those of normal controls. With regard to bone turnover urinary crosslink measurements are of minor importance in CRF. In contrast, serum measurements could be helpful in revealing bone resorption both in patients with CRF and those under dialysis treatment.

Adult↗

Hydrogen peroxide for prevention of bacterial growth on polymer biomaterials.

BACKGROUND: Despite widespread use of potent antibiotics, infections of artificial implants and catheters are of increasing concern. We tested whether local treatment with 3% hydrogen peroxide (H2O2), long known as an inexpensive wound disinfectant, could prevent or reduce bacterial growth on polymer biomaterials. METHODS: Two-centimeter-long pieces of polyurethane and silicone tubing were contaminated with a standardized solution of Staphylococcus epidermidis (10(5)/mL) and then rinsed and wiped with saline (0.9%) solution. Bacterial growth was assessed after incubation at 37 degrees C for 24 hours. Bacterial colonies were compared for the following treatments: wiping only with saline; wiping with 1.5%, 2%, or 3% H2O2; pretreating biomaterials with 3% H2O2 and subsequent contamination for 2 and 4 hours without treatment after contamination; and contamination of tubings 1 month after pretreatment with 3% H2O2. The effect of 3% H2O2 was also assessed on contamination with Escherichia coli. RESULTS: Bacterial growth was reduced by more than 99% when the contaminated tubes were treated with 3% H2O2 compared with saline control (p < 0.001). Lower concentrations of H2O2 were less effective. The length of the contamination period had no influence on the effectiveness of H2O2 when used on polyurethane but did with silicone tubings. Pretreatment with H2O2 1 month before contamination still reduced bacterial growth rate by 90% on polyurethane and by 75% on silicone tubings. Comparable effects on bacterial growth rate were observed for staphylococci (-90%, p < 0.001) and escherichiae (-90%, p < 0.001). CONCLUSIONS: Local treatment with 3% H2O2 significantly reduced bacterial growth on polymer biomaterials even for 1 month after treatment. This finding might influence clinical strategies of prevention of foreign body infection.

Anti-Infective Agents, Local↗

Associative database of protein sequences.

MOTIVATION: We present a new concept that combines data storage and data analysis in genome research, based on an associative network memory. As an illustration, 115 000 conserved regions from over 73 000 published sequences (i.e. from the entire annotated part of the SWISSPROT sequence database) were identified and clustered by a self-organizing network. Similarity and kinship, as well as degree of distance between the conserved protein segments, are visualized as neighborhood relationship on a two-dimensional topographical map. RESULTS: Such a display overcomes the restrictions of linear list processing and allows local and global sequence relationships to be studied visually. Families are memorized as prototype vectors of conserved regions. On a massive parallel machine, clustering and updating of the database take only a few seconds; a rapid analysis of incoming data such as protein sequences or ESTs is carried out on present-day workstations. AVAILABILITY: Access to the database is available at http://www.bioinf.mdc-berlin.de/unter2.html++ + CONTACT: (hanke,lehmann,reich)@mdc-berlin.de; bork@embl-heidelberg.de

Amino Acid Sequence↗

cAMP-dependent protein kinase is in an active state in rat small arteries possessing a myogenic tone.

The hypothesis that cAMP-dependent protein kinase (protein kinase A; PKA) is in an active state in small arteries possessing a myogenic tone was investigated in pressurized rat tail small arteries. At a pressure of 80 mmHg, these vessels constricted to 71.6 +/- 1.0% (n = 32) of the diameter of the fully relaxed state. The PKA inhibitors Rp-8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphothioate (Rp-CPT-cAMPS) and N-(2-([3-(4-bromophenyl)-2-propenyl]amino)-ethyl)-5- isoquinolinesulfonamide HCl (H-89) constricted these vessels dose dependently. For example, 300 microM Rp-CPT-cAMPS and 9 microM H-89 reduced vessel diameter by 11.0 +/- 1.2% (n = 8) and 14.3 +/- 3.6% (n = 5), respectively. The cGMP-dependent protein kinase (protein kinase G; PKG) inhibitor Rp-8-bromo-beta-phenyl-1,N(2)-etheno-guanosine 3', 5'-cyclic monophosphothioate (Rp-8-Br-PET-cGMPS) did not alter vessel diameter up to a concentration of 10 microM. Neither endothelium removal nor inhibition of neural transmission affected the action of Rp-CPT-cAMPS. The effect of 300 microM Rp-CPT-cAMPS was reduced by 82% after pretreatment of the vessel with 100 nM iberiotoxin, a blocker of calcium-activated potassium (K(Ca)) channels. However, the effect of 300 microM Rp-CPT-cAMPS was not altered after pretreatment with 1 mM 4-aminopyridine, a blocker of delayed rectifier potassium channels, or 10 microM ryanodine, a blocker of ryanodine receptor-generated calcium sparks. In inside-out patch-clamp experiments on cells isolated from rat tail small arteries, 10 U/ml of the catalytic subunit of PKA together with 100 microM MgATP increased K(Ca) channel activity 30.1 +/- 9. 8-fold (n = 9). Additionally, neither inhibition of PKA or PKG nor moderate activation of PKA or PKG altered the vessel response to a pressure step from 80 to 120 mmHg. These results suggest that in rat tail small arteries possessing a myogenic tone 1) PKA is in an active state modulating the level of the myogenic tone, and 2) K(Ca) channels mediate, at least partly, this effect of PKA.

Animals↗