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Biomedical subjects

M Langer

Publications and source records attributed to M Langer.

At least 199 records · Page 11Linked to original sources
PubMed1995

Noncavernomatous portal vein thrombosis in hepatic cirrhosis: treatment with transjugular intrahepatic portosystemic shunt and local thrombolysis.

PURPOSE: To evaluate the use of the transjugular intrahepatic portosystemic shunt (TIPS) and local, low-dose thrombolysis in the treatment of complete, noncavernomatous portal vein occlusion. MATERIALS AND METHODS: TIPS implantation and portal vein recanalization was attempted in seven patients with noncavernomatous portal vein obstruction and recurrent variceal bleeding. TIPS placement was followed by thrombolytic therapy to restore portal venous blood flow. Hemodynamic effects and clinical characteristics after the procedure and during follow-up were assessed. RESULTS: The implantation of TIPS and the recanalization of the portal vein trunk were successful in all patients. The treatment reduced the portal venous pressure gradient and restored portal blood flow. No bleeding complications were observed. CONCLUSION: TIPS placement and recanalization of the main portal vein is a safe and effective treatment option for patients with liver cirrhosis and noncavernomatous portal vein occlusion.

Combined Modality Therapy↗
PubMed1995

Budd-Chiari syndrome: technical, hemodynamic, and clinical results of treatment with transjugular intrahepatic portosystemic shunt.

PURPOSE: To evaluate use of the transjugular intrahepatic portosystemic shunt (TIPS) as a nonsurgical approach for the management of Budd-Chiari syndrome (BCS). MATERIALS AND METHODS: Twelve patients with fulminant (n = 2), subacute (n = 5), or chronic (n = 5) BCS underwent TIPS placement. Hepatic venous obstruction was demonstrated at computed tomography and color duplex sonography. BCS was confirmed histologically in all patients. Hemodynamic parameters and clinical characteristics were assessed. RESULTS: TIPS creation was successful in all patients. Treatment reduced the portal venous pressure gradient by 75% and resulted in a mean shunt flow of 2,300 mL/min +/- 650 (standard deviation). No serious procedure-related complications were observed. The two patients with fulminant BCS died of septicemia or progressive liver failure despite intervention. The other 10 patients showed clinical improvement with reduction or disappearance of ascites. During follow-up, shunt dysfunction occurred in five of 10 patients with recurrence of ascites requiring repeat intervention. CONCLUSION: TIPS placement is safe and effective in patients with portal hypertension caused by subacute or chronic BCS.

Acute Disease↗
PubMed1995

Digital optical card. A promising technology for documentation and communication of images.

PURPOSE: To assess a patient-oriented digital optical card (OC) for documentation and communication of images using the analysis of breast microcalcifications to illustrate its resolution power. METHODS: Fifty film mammograms with histologically proved clustered microcalcifications were digitized using a 5 lp/mm CCD-scanner. A region of interest containing the cluster was selected for documentation on an OC as an overview OC-image and as a magnified OC-image (5 lp/mm). The shape (spherical/nonspherical) as well as the total number of microcalcifications were quantitatively analyzed by 2 radiologists. RESULTS: The detection rate for total number of overall and spherical microcalcifications using digital media was significantly reduced (p < 0.01) compared to analog mammography. There were no significant differences in the detection rate of nonspherical microcalcifications between film mammograms (100%) and magnified section OC-images (92.7%). The overview OC-image revealed 72% of those calcifications (p < 0.01). CONCLUSION: According to our results, this technology is not appropriate for diagnosis of breast microcalcifications, but may be a promising communication digital medium for transmitting an image/report unit to referring physicians.

Breast Neoplasms↗
PubMed1995

Bioequivalence and absolute bioavailability of oblong and coated levomepromazine tablets in CYP2D6 phenotyped subjects.

The bioequivalence and absolute bioavailability of oblong and coated levomepromazine tablets were studied in 12 healthy volunteers. A 1-hour intravenous infusion served as the reference. Serum concentrations of levomepromazine were quantified with a specific high-performance liquid chromatographic method and electrochemical detection. The 2 oral formulations were bioequivalent. After oral administration of oblong and coated levomepromazine tablets the mean serum concentration versus time profiles were similar and the pharmacokinetic parameters showed wide interindividual variations. There was a 21% absolute bioavailability of levomepromazine, indicating a pronounced presystemic metabolism. The total serum clearance and the apparent volume of distribution at steady state were 48 +/- 14 l/min and 980 +/- 213 l, respectively. These pharmacokinetic parameters were also investigated with respect to the CYP2D6 polymorphism, i.e. via dextromethorphan phenotyping of 9 subjects, 3 subjects were poor metabolizers, and 6 extensive metabolizers. The Spearman's rank-ordered correlation analysis did not reveal a significant correlation between the pharmacokinetic parameters AUC, Cmax and t1/2 after oral administration of oblong and coated levomepromazine tablets and the metabolic ratios of dextromethorphan, suggesting that levomepromazine is not metabolized to any major extent by the isoenzyme CYP2D6.

Administration, Oral↗
PubMed1994

Histidine ammonia-lyase mutant S143C is posttranslationally converted into fully active wild-type enzyme. Evidence for serine 143 to be the precursor of active site dehydroalanine.

Histidase [histidine ammonia-lyase (HAL); EC 4.3.1.3] from Pseudomonas putida is a homotetramer and contains one catalytically essential dehydroalanine residue per subunit. Since the mutant S143A was catalytically inert, it has been proposed that serine 143 is the precursor of the active site dehydroalanine [Langer et al. (1994) Biochemistry 33, 6462-6467]. To further define the role of serine 143, we prepared the mutants S143T and S143C by site-directed mutagenesis. The threonine 143 mutant was neither catalytically active (< 0.01%) nor did it form with L-cysteine and oxygen a product absorbing at 340 nm. In contrast, the cysteine 143 mutant showed full catalytic activity and, after treatment with L-cysteine and oxygen, an increased absorbance at 340 nm similar to that of the wild-type enzyme. Also the kinetic constants (Km and Vmax) were identical with those of wild-type histidase. Titration with Ellman's reagent revealed that both wild-type and S143C mutant histidase contained seven thiol groups after exhaustive reduction. It must be concluded that posttranslational modification occurs with both serine 143 and cysteine 143 by elimination of water and hydrogen sulfide, respectively. In both cases dehydroalanine is formed and the resulting histidases are indistinguishable. In contrast, the threonine 143 mutant is not processed to active enzyme.

Alanine↗
PubMed1994

Identification of serine-143 as the most likely precursor of dehydroalanine in the active site of histidine ammonia-lyase. A study of the overexpressed enzyme by site-directed mutagenesis.

The gene coding for histidase (histidine ammonia-lyase, HAL, EC 4.3.1.3) was isolated from a lambda-EMBL3 genomic library from Pseudomonas putida nicII and subcloned into the expression vector pT7-7. Transformation of Escherichia coli BL21 (DE3) cells with the recombinant vector led to the expression of catalytically active histidase amounting to 20-30% of the total soluble protein in the crude cell extract. A new rapid and highly efficient isolation procedure is described leading to electrophoretically homogeneous histidase within 1.5 days. Six grams of E. coli BL21 (DE3) cells (wet weight) gives approximately 100 mg of homogeneous histidase with a specific activity of 27 IU/mg. To investigate the possible role of serine as a precursor of dehydroalanine in the active site of histidase, each of the four serines, conserved in all known histidases and phenylalanine ammonia-lyases, was consecutively changed to alanine by site-directed mutagenesis. The resulting mutant genes were subcloned into the expression vector pT7-7 and were assayed for histidase activity. The catalytic activities of the four mutants and of wild-type histidase were compared. The Km and Vmax values of the overexpressed mutants S112A, S393A, and S418A and wild-type histidase did not show any significant differences. Mutant S143A, however, was devoid of catalytic activity (< 0.01%), pointing to the outstanding importance of this serine for the formation of an active enzyme. We conclude that serine-143 is the most probable precursor of the active-site dehydroalanine. The role of serine-143 in the biosynthesis of active histidase is discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗
PubMed1994

[Gastroesophageal reflux. Pathophysiology, diagnosis and rational therapy].

A combination of the typical symptoms heartburn and regurgitation may be considered virtual proof of gastroesophageal reflux disease. In the case of the atypical symptoms dysphagia, odynophagia, pharingitis, reflux-induced attacks of respiratory distress and intermittent chest pain further diagnostic investigation is indicated. Endoscopy reveals patchy reddening and possibly erosions, ulcers and strictures. Although the decisive pathophysiological factor in reflux disease is motility, the use in particular of acid suppressors represents an important part of treatment; in more severe reflux esophagitis (grades III and IV), proton pump inhibitors are the drugs of first choice. Gastro-esophageal reflux disease is a chronic condition with a recurrence rate of 60-80 percent. For prophylaxis, the minimum dose of antacids required to treat the stage must be administered.

Esophagogastric Junction↗
PubMed1994

Diagnosis of bacterial infection in the ICU: general principles.

Diagnosis and treatment of infection is a common procedure in the clinical management of patients in the ICU. Infection in the ICU is an important area for study, but requires well-defined and proven diagnostic criteria. The diagnosis of infection, like any diagnosis, is based on probability, and diagnostic criteria are therefore selected according to the physician's objectives and the acceptable margin of error. It is easier to diagnose correctly a full-blown, severe bacterial infection than one that is just beginning, and the same criteria cannot be used to identify accurately both conditions. We should diagnose an infectious complication at the time it needs treatment, but there is often a lack of clear objectives in the diagnostic process, and up to now, few reliable criteria have been available. Before considering the sensitivity and specificity of single diagnostic procedures it is important to trace the evolution of the infection. The problem may be approached in two steps, by describing or defining (i) the minimum level of severity of a probable infection which requires/justifies specific treatment as the first end-point of the diagnosis, and (ii) the ways the diagnosis may be confirmed using the best available procedure (which might not be always available or applicable in all cases in the short term).

Bacterial Infections↗
PubMed1994

Pharmacokinetics and bioavailability of benperidol in schizophrenic patients after intravenous and two different kinds of oral application.

Pharmacokinetics and bioavailability of benperidol were determined in 13 schizophrenic patients after acute administration of 6 mg benperidol as an intravenous (i.v.) bolus injection, orally as liquid, and orally as tablets using a partially randomized cross-over design. Drug plasma levels were determined by high performance liquid chromatography with electrochemical detection and subjected to model independent pharmacokinetic analyses. After i.v. dosing the geometric means (mean-g) were 3.2 min for the distribution half-life, 5.80 h for the elimination half-life (t1/2 beta), 4.21 l/kg for the distribution volume, 7.50 h for the mean residence time (MRT), and 0.50 l/(h*kg) for the clearance. After oral administration as liquid and as tablet mean-g data for the time lag until the first appearance of measurable plasma concentrations were 0.33 and 1.1 h, mean-g t1/2 beta values were 5.5 and 4.7 h, respectively, mean-g tmax data were 1.0 h and 2.7 h, mean-g MRT values were 8.44 and 8.84 h, and mean-g Cmax maxvalues were 10.2 and 7.3 ng/ml. Differences between liquid and tablet administration were statistically significant for time lag, tmax, and Cmax. Mean-g absolute bioavailabilities were computed as 48.6% after liquid and 40.2% after tablet administration respectively. All parameters studied exhibited large intersubject variation. The plasma concentrations of the presumed metabolite "reduced benperidol" were found to be very low.

Administration, Oral↗
PubMed1994

Prognostic value of the activated partial thromboplastin time after orthotopic liver transplantation. A prospective study.

In this prospective study, we evaluated the predictive value of activated partial thromboplastin time on day 8 post transplantation for event-free survival in patients who had had orthotopic liver transplants; both death and retransplantation within 6 months were the events considered. In a 4-year period, 109 patients had orthotopic liver transplants in our hospital, and 104 were eligible for the study since they survived and were not given new transplants within 8 days. The activated partial thromboplastin time was significantly longer in patients who survived event-free for less than 6 months than in those with longer event-free survivals. Kaplan-Meier curves showed that patients with normal activated partial thromboplastin times were nine times more likely to survive more than 6 months without events than patients with prolonged values. The positive predictive value of activated partial thromboplastin time for event-free survival was 88% and the negative predictive value was 54%, indicating that the test is useful for predicting patient outcome. We suggest that activated partial thromboplastin time be performed on day 8 post transplantation to predict the medium-term event-free survival.

Adolescent↗
PubMed1994

Proton magnetic resonance spectroscopy studies on human brain myo-inositol in hypo-osmolarity and hepatic encephalopathy.

BACKGROUND/AIMS: Recent in vivo studies using proton magnetic resonance (1H-MR) spectroscopy showed low levels of myo-inositol in the brain in hepatic encephalopathy; the pathogenetic relevance of this observation is unclear. METHODS: Myo-inositol and glutamine levels in the brain were studied in vivo by 1H-MR spectroscopy in patients with hypo-osmolarity and hepatic encephalopathy. RESULTS: A patient with severe plasma hypo-osmolarity (222 mOsm/L) had almost undetectable signals for myo-inositol and glutamine/glutamate in the brain. Both signals reappeared after normalization of plasma osmolarity, suggesting that both myo-inositol and glutamine were released as organic osmolytes from the brain. A decreased cerebral myo-inositol signal is also found in low-grade hepatic encephalopathy but is accompanied by an increased glutamine signal. Cirrhotics without hepatic encephalopathy have near-normal inositol signals, and patients with acquired immunodeficiency syndrome encephalopathy have increased inositol signals. CONCLUSIONS: The 1H-MR spectroscopic myo-inositol signal in the human brain predominantly reflects an osmosensitive inositol pool. It is hypothesized that its depletion in latent hepatic encephalopathy points to a disturbance of cell volume homeostasis in the brain as an early pathogenetic event. This may partly be caused by a hyperammonemia-induced glutamine accumulation in the brain.

Acquired Immunodeficiency Syndrome↗
PubMed1994

[The value of a new digital laser card for image/report documentation and transmission].

The capabilities of a patient-oriented digital optical laser-card for the documentation of the image/report unit and for image transmission were assessed. 150 conventional X-rays covering the fields of urology (n = 50), traumatology (n = 50) and orthopaedics (n = 50) were digitised using a CCD scanner and subsequently transmitted to an Image-Transfer Medium (ITM) and to an optical laser-card. The image quality for the detection of relevant diagnostic parameters was evaluated by 4 radiologists and one clinician of the corresponding specialty. Based upon a total of 4740 decision readings for each method, it was found that the optical laser-card reduced the image quality significantly (p < 0.01) in comparison to the digitised ITM images in all fields. Thus, a primary diagnostic statement cannot be made based upon the images of the optical card. However, concomitant documentation of the image and opinion on the card may be used for the transmission of the radiological report, especially to external referring institutions.

Documentation↗
PubMed1994

[Functional spectroscopy: the limits and potentials of a new method for the study of brain activation with MR tomography].

The possibility of examining brain activity by means of localised spectroscopy was studied in relation to its neurological basis. Measurements on 18 normals during optical stimulation showed an improvement in signal to noise ratio compared with functional imaging of almost one order of magnitude. Time dependent measurements during stimulation by a 500 ms light impulse showed definite delay of increased blood flow when compared with oxygen utilisation. The excellent signal to noise ratio and the inherent stability of the method permits reliable detection of weak effects such as are caused by finger tapping or electrical stimulation.

Artifacts↗