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Biomedical subjects

M Langer

Publications and source records attributed to M Langer.

At least 19 recordsLinked to original sources

Comparison of simulated annealing algorithms for conformal therapy treatment planning.

PURPOSE: The efficiency of four fast simulated annealing algorithms for optimizing conformal radiation therapy treatment plans was studied and the resulting plans were compared with each other and to optimized conventional plans. METHODS AND MATERIALS: Four algorithms were selected on the basis of their reported successes in solving other minimization problems: fast simulated annealing with a Cauchy generating function, fast simulated annealing with a Lorentzian generating function, variable step size generalized simulated annealing (VSGSA), and very fast simulated reannealing (VFSR). They were tested on six clinical cases using a multiple beam coplanar conformal treatment technique. Relative beam weights were computed that maximized the minimum tumor dose subject to dose-volume constraints on normal organ doses. Following some initial tuning of the annealing parameters, each algorithm was applied identically to each test case. Optimization tests were run using different random number sequences and different numbers of iterations. RESULTS: The VSGSA algorithm consistently produced the best results. Using long run times, it generated plans with the highest minimum tumor dose in five of the six cases. For the short run times, the VSGSA solutions averaged larger minimum tumor doses than those of the other algorithms for all six patients, with increases ranging from 0.4 to 5.9 Gy. For three of the patients, the conformal plan gave a clinically significant increase in the minimum tumor dose over the conventional plan, ranging from 8.2 to 13.0 Gy. In two other cases, there was little difference between the two treatment approaches. For one case, the optimized conventional plan was much better than the conformal plan because the conventional beam arrangement included wedges, which offset the multiple beam advantage of the conformal plans. CONCLUSIONS: For equal computing times of both long and short duration, the VSGSA algorithm consistently produced conformal plans that were superior to those produced by the other algorithms. The simple conformal technique used in this study showed a significant potential advantage in the treatment of abdominal tumors. In three of the cases, the conformal plans showed clinically important increases in tumor dose over optimized conventional plans.

Abdominal Neoplasms

The transjugular intrahepatic portosystemic stent-shunt procedure for refractory ascites.

BACKGROUND: Previous studies have suggested that the transjugular placement of an intrahepatic stent to establish a portosystemic shunt is an effective treatment of uncomplicated ascites accompanying variceal bleeding. We studied the stent shunt for use in patients with liver cirrhosis and ascites refractory to medical treatment. METHODS: Fifty of 62 consecutive patients with cirrhosis and refractory ascites (18 with Child-Pugh class B liver disease and 32 with class C) were treated with the stent shunt--an expandable stent of metallic mesh placed between a major branch of the portal vein and one of the hepatic veins. Patients were followed for a mean (+/- SD) of 426 +/- 333 days. Those with advanced cancer, severe heart failure, or severe liver failure were excluded. RESULTS: The stent shunt was successfully placed in all patients and reduced the pressure gradient between the portal vein and the inferior vena cava by an average of 63 percent. Thirty-seven patients (74 percent) had complete responses (total remission of ascites within three months), and nine patients (18 percent) had partial responses (ascites detected by ultrasound but with no need for paracentesis). Four patients did not respond, including two who died within two weeks of shunt placement. After the procedure, 25 patients had hepatic encephalopathy, as compared with 20 patients before the procedure; although encephalopathy improved in 3 patients, new encephalopathy developed in 8 patients. In the 28 of the 33 patients followed for more than six months who were evaluated, the mean serum creatinine concentration was 1.5 +/- 0.09 mg per deciliter (133 +/- 8 mumol per liter) before placement of the stent shunt, 1.5 +/- 1.6 mg per deciliter (133 +/- 141 mumol per liter) one week after the procedure, and 0.9 +/- 0.3 mg per deciliter (80 +/- 27 mumol per liter) after six months (P = 0.008 for the comparison of concentrations before and six months after the procedure). Renal function did not improve in the six patients with organic kidney disease. Procedure-related complications developed in 16 patients, including intraabdominal bleeding requiring blood transfusions in 2 patients. Thrombotic occlusion of the stent shunt occurred within two weeks in 5 patients, and later insufficiency of the shunt occurred in 16 patients, including 12 with recurrence of ascites after complete remission. During followup, an additional 29 patients died--10 of progressive liver disease and 19 of other causes. Survival for at least one year was associated with a patient's being under 60 years of age, having a serum bilirubin level before placement of the stent shunt of less than 1.3 mg per deciliter (22 mumol per liter), and having a complete response. CONCLUSIONS: Our findings in an uncontrolled prospective study suggest that the transjugular intrahepatic porto-systemic stent-shunt procedure was an effective treatment for many patients with liver cirrhosis and refractory ascites, but mortality from underlying diseases was substantial.

Ascites

Very fast simulated reannealing in radiation therapy treatment plan optimization.

PURPOSE: Very Fast Simulated Reannealing is a relatively new (1989) and sophisticated algorithm for simulated annealing applications. It offers the advantages of annealing methods while requiring shorter execution times. The purpose of this investigation was to adapt Very Fast Simulated Reannealing to conformal treatment planning optimization. METHODS AND MATERIALS: We used Very Fast Simulated Reannealing to optimize treatments for three clinical cases with two different cost functions. The first cost function was linear (minimum target dose) with nonlinear dose-volume normal tissue constraints. The second cost function (probability of uncomplicated local control) was a weighted product of normal tissue complication probabilities and the tumor control probability. RESULTS: For the cost functions used in this study, the Very Fast Simulated Reannealing algorithm achieved results within 5-10% of the final solution (100,000 iterations) after 1000 iterations and within 3-5% of the final solution after 5000-10000 iterations. These solutions were superior to those produced by a conventional treatment plan based on an analysis of the resulting dose-volume histograms. However, this technique is a stochastic method and results vary in a statistical manner. Successive solutions may differ by up to 10%. CONCLUSION: Very Fast Simulated Reannealing, with modifications, is suitable for radiation therapy treatment planning optimization. It produced results within 3-10% of the optimal solution, produced using another optimization algorithm (Mixed Integer Programming), in clinically useful execution times.

Algorithms

Breath-hold projection magnetic resonance-cholangio-pancreaticography (MRCP): a new method for the examination of the bile and pancreatic ducts.

Breath-hold MR cholangio-pancreaticography using the RARE method was evaluated as a noninvasive alternative to direct cholangio-pancreaticography in 30 healthy volunteers and in 30 patients with various diseases of the respective duct systems. In contrast to 3D MR cholangiography, RARE MRCP generates projection images requiring a 4-s acquisition time and no postprocessing. Diagnostic information gained from the cholangio-pancreaticograms was fully equivalent to that of conventional x-ray imaging by invasive procedures. Additional information was gained whenever endoscopic access was impossible and/or cystic malformations were present.

Adult

Haemangiomatosis in children: value of MRI during therapy.

MRI findings of 18 examinations of six children with haemangiomatosis and one with extended arteriovenous malformation are reported. Structures involved were the liver, liver and lung, periorbital area and the thigh. Response to interferon therapy, in particular, was assessed. With MRI the disease can be characterized and the extent of the lesions and size of the haemangiomas measured. Coronal views provide excellent demonstration of the involved structures in liver and lung haemangiomatosis. Two children showed response to interferon therapy with a reduction in lesion size and subsequently in number. Signal intensity decreased slightly on T2-weighted images. During treatment, however, no definitive fibrotic zones were seen. Following complete regression, signal intensity of the liver parenchyma was homogeneous in both weightings, that is, no fibrotic areas were visible 18 months after the beginning of treatment. Two children showed no response and one child died from congestive cardiac failure. The periorbital haemangioma was reduced in size and the lesion in the thigh might be classified as an arteriovenous malformation. In children MRI can replace CT as it is a reliable imaging modality for diagnosing haemangiomatosis and monitoring therapy.

Child

Value of RARE-MRI sequences in the diagnosis of lymphangiomatosis in children.

Three patients suffering from extensive cavernous lymphangiomatosis are presented here. They were examined by MRI using RARE-MR hydrography (rapid acquisition with relaxation enhancement) as well as conventional spin-echo sequences. RARE sequences, which depict each fluid-filled lymphatic space, can be used for screening. RARE-sequences help to shorten investigation time, particularly in cases involving the skeleton. The imaging strategy can be changed according to the results of this sequence. It may be performed prior to spin-echo sequences and facilitates follow-up investigations. RARE sequences distinguish between lymphangiomatosis and hemangiomatosis, or a combination of the two.

Adult

[NMR tomographic measurement of femoral ante-torsion and tibial torsion].

PURPOSE: A new MRI method for the measurement of femoral torsion and tibial torsion is presented. METHODS: Axial images were generated using a standard gradient echo sequence (FLASH 2D). Otherwise measurement of femoral and tibial torsion was performed according to an established CT method. RESULTS: The torsion angles measured using MRI were in accordance with the angles measured using the CT method. The MRI method was not more time-consuming than the CT method. CONCLUSION: In respect of radiation exposure, MRI determination of femoral and tibial torsion should be considered particularly in children and patients who have to undergo repeated torsion measurements.

Adolescent

[Psychosocial prognostic factors for refertilization or IvF after tubal sterilization].

In a psychosomatic study we interviewed 33 women who had undergone tubal anastomosis or IvF after tubal ligation. As a control group we chose a randomised sample of 45 women after elective tubal ligation. We used a semi-structured interview and the Giessen-test as psychometric instruments. According to the leading indication for reanastomosis, we allocated women to one of 2 groups: 21 patients had found a new partner (R-partner), 12 mentioned experiences of loss (R-loss). The groups were well comparable in respect of sociodemographic items, but showed relevant differences in psychological variables, like motivation for and time for deliberation to sterilisation or age difference between partners. Women of the R-partner group were highly satisfied with tubal reanastomosis as compared to R-loss subjects. Satisfaction with the procedure was basically independent of an actual pregnancy. Women experienced the two methods in different, rather specific ways. Cluster analysis of the Giessen-test result confirmed group allocation. We conclude that experiences of loss as a leading reason for tubal reanastomosis are unfavourable prognostic factors. IvF has an unfavourable prognosis in women with the intention to restore the mutilated body image. Preoperative counselling by a psychotherapeutically trained counsellor seems mandatory.

Adult

[Uterus unicornis with rudimentary horn and ipsilateral kidney agenesis: clinical symptoms and therapy].

We report on a 21-year old patient with unicornuate uterus with a rudimentary non-communicating horn (Buttram II-A-1-b), haematosalpinx, associated with ipsilateral ureteranomaly and renal agenesis. In this case we illustrate symptoms, diagnosis and therapy. Despite extensive diagnosis surgical methods finally have to be adapted to the anatomical situation during operation. A short review of literature and embryology is given, more diagnostic preoperative measures are discussed.

Adult

The reducing stent: treatment for transjugular intrahepatic portosystemic shunt-induced refractory hepatic encephalopathy and liver failure.

PURPOSE: To examine the efficacy of a stent device in reducing the diameter of transjugular intrahepatic portosystemic shunts (TIPS) in patients with progressive liver failure or with shunt-induced hepatic encephalopathy. MATERIALS AND METHODS: Seven patients with TIPS (four with severe hepatic encephalopathy, three with progressive liver failure) underwent transjugular implantation of a stent designed to reduce the flow through the original TIPS channel. RESULTS: Implantation of the reducing stent proceeded without complication. Duplex sonography showed that stent flow decreased by 41% +/- 18 (mean +/- standard deviation). The four patients with hepatic encephalopathy showed substantial improvement. Concentrations of plasma ammonium and serum bilirubin improved considerably. In contrast, functional impairment progressed in the three patients treated for liver failure. The patients soon died. CONCLUSION: With the limited experience of treating these seven patients, the authors suggest that shunt-induced hepatic encephalopathy can be effectively treated with implantation of a reducing stent. Hepatic failure, however, is a deleterious complication that seems to be irreversible.

Aged

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

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

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

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

[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