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Biomedical subjects

J Richter

Publications and source records attributed to J Richter.

At least 109 records · Page 6Linked to original sources
PubMed1999

Pulmonary ischemia/reperfusion injury: a quantitative study of structure and function in isolated heart-lungs of the rat.

Early graft dysfunction after lung transplantation is a significant and unpredictable problem. Our study aimed at a detailed investigation of structure-function correlations in a rat isolated heart-lung model ofischemia/ reperfusion injury. Variable degrees of injury were induced by preservation with potassium-modified Euro-Collins solutions, 2 hr of cold ischemia, and 40 min of reperfusion. Pulmonary artery pressure (Ppa), pulmonary vascular resistance (PVR), peak inspiratory pressure (PIP), and perfusate gases (deltaPO2, deltaPCO2) were recorded during reperfusion. Right lungs were used to calculate W/D-weight ratios. Nineteen experimental and six control left lungs were fixed for light and electron microscopy by vascular perfusion. Systematic random samples were analyzed by stereology to determine absolute and relative volumes of lung structures, the amount of interstitial and intraalveolar edema, and the extent of epithelial injury. Lectin- and immunohistochemistry using established epithelial cell markers were performed in three animals per group to reveal sites of severe focal damage. Experimental lungs showed a wide range in severity of ischemia/ reperfusion injury. Intraalveolar edema fluid amounted to 77-909 mm3 with a mean of 448+/-250 mm3 as compared with 22+/-22 mm3 in control lungs (P<0.001). Perfusate oxygenation (deltaPO2) decreased from 30.5+/-15.2 to 21.7+/-15.2 mm Hg (P=0.05) recorded after 5 and 40 minutes of reperfusion. In experimental lungs, a surface fraction of 1% to 58% of total type I pneumocyte surface was damaged. Intraalveolar edema per gas exchange region (Vv ape,P) and deltaPO2 were related according to deltaPO2 = 96 - 60 x log10(Vv ape,P) [mm Hg]. The extent of epithelial injury did not correlate with deltaPO2 nor with intraalveolar edema, but increased significantly with PVR. Lectin- and immunohistochemistry revealed focal severe damage to the alveolar epithelium at the border of perivascular cuffs.

Animals↗
PubMed1999

Chromosomal imbalances in small cell carcinomas of the urinary bladder.

Small cell carcinomas (SCCs) represent a rare histological subtype of urinary bladder cancer. Little is known abut the genetic alterations in these tumours. To identify chromosomal aberrations that are typically present in SCC of the urinary bladder, ten tumours were analysed by comparative genomic hybridization (CGH). CGH allows screening for all relative DNA copy number gains and losses present in a tumour. SCCs of the bladder were characterized by a high number of genomic alterations (mean: 11.3 per tumour). Deletions were most frequent at 10q (7 of 10 tumours deleted), 4q, 5q (5/10 each), and 13q (4/10). These regions may carry tumour suppressor genes with relevance for this particular tumour type. Gains of DNA sequences were most prevalent at 8q (5/10), 5p, 6p, and 20q (4/10 each). High level amplifications were found at 1p22-32, 3q26.3, 8q24, and 12q14-21. These loci may pinpoint the localization of oncogenes with relevance for small cell bladder cancer. The analysis of one tumour having areas of both SCC and transitional cell carcinoma strongly suggests that SCC can develop from TCC through the acquisition of additional genetic alterations.

Carcinoma, Small Cell↗
PubMed1999

Improvement of rat lung structure and function after preservation with celsior.

Ischemia/reperfusion-induced increase in pulmonary microvascular permeability was shown to be reduced after preservation with Celsior. We investigated reimplantation-induced lung injury in isolated, reperfused rat lungs after preservation via the pulmonary artery with Celsior, Celsior + prostacyclin, and reduced-potassium (40 mmol) Euro-Collins solution (40 ml/kg/body wt each) followed by 2 h of cold ischemia. Arterial and veneous oxygen tensions were recorded during 50 min of in vitro reperfusion after which the lungs (10 right lungs per experimental group) were fixed by vascular perfusion. The tissue was further processed for microscopy, and histological changes were quantified stereologically. Lung preservation with Celsior resulted in a significantly higher volume of air-filled alveolar space with a large proportion of widely distended alveoli compared with the other groups. In the Euro-Collins group the fraction of atelectatic alveoli exceeded that observed in Celsior-preserved lungs. In accordance, the difference between arterial and venous oxygen tensions was significant among Euro-Collins- and Celsior-protected lungs, with improved oxygenation values in the Celsior group. In contrast, addition of prostacyclin to Celsior treatment resulted in rather variable structural as well as functional data. There were no differences in the volumes of intraalveolar edema among the groups tested. However, the volume of alveolar tissue was increased in the Euro-Collins group. In conclusion, compared with Euro-Collins and Celsior + prostacyclin solutions, preservation with Celsior resulted in improved structural characteristics which in combination with improved oxygenation parameters supports the prospective advantage of Celsior in clinical organ preservation.

Animals↗
PubMed1999

[Supination trauma. A classic case].

Sprains in the lateral ligaments of the ankle produce the most common ligamentous injuries of the human body. The mechanism of injury is complex, while supination represents the main component of foot movement. Classifying lateral ankle ligament injuries, many authors use a system of three degrees, which includes mild, moderate and severe sprains. Despite this scientific categories, in our opinion is the differentiation between elongation and complete ruptures of practical relevance. Under a biomechanical point of view, ligamentous trauma of the lateral ligaments lead to acute antero-lateral rotational instability (ALRI). Following the retrospective clinical study of Zwipp with 1,235 patients, in 70% of complete disruptions, the anterior talo-naviculare and fibulocalcanear ligaments are involved together. Syndesmotic injuries have been reported at a rate up to 10% of ankle sprains with deltoid ligaments at 2.5%. Rarely, the classic ankle sprain leads to injuries which affect the foot on a so called "supination fracture line". A rate of 7.4% is reported for these accompanying injuries. Therefore, clinical examination of ankle sprains should not only address on the distal tip of the fibula. Critical bony and ligamentous structures like the fifth metatarsal base, the calcaneo-cuboideal ligament, the ligaments of the anterior calcaneal process, the talus and syndesmotic ligaments have to be screened for pain and swelling. In our opinion, careful clinical examination and plain radiographs in two plains are sufficient for diagnosing ankle sprains and functional therapy.

Acute Disease↗
PubMed1999

[Stable ankle joint fractures. Indication for surgical or conservative management?].

In German literature, ankle joint fractures are mostly classified in three groups according to Weber. In cases of the type A, the fracture line runs below, in cases of type B at height of the syndesmotic ligaments. C-type fractures are typically seen above this region. However, this practical and simple classification allows no inferences at accompanying injuries which in turn influence the functional outcome. We observed isolated fractures of the lateral malleolus in more than 60% of all type B-fractures, as soon as in the majority the type A-fractures. Since isolated medial ankle fractures occur very rarely, careful exclusion of further injuries is advisable here. In order to differentiate stable ones from unstable type B ankle injuries, we carry out a manual stress test, if there is less than 2 mm fracture dislocation and a congruent ankle mortise. In this manner we could find that stable lateral ankle fractures are characterized with a combination of an intact dorsal syndesmotic and medial ligament. Stable type B and undisplaced type A fractures were treated conservatively with an ankle brace (Aircast?). Unstable ankle injuries were treated by ORIF. Conservative treatment for undisplaced medial malleolar fractures is recommended, if x-rays showed less than 2 mm dislocation which allows a tibio-talare impingement. Biomechanical investigations could prove a significant increase in ankle joint stability, when an axial load of 300 N was applied to various horizontal loads. The talus does not follow automatically a displaced fibular fracture. The dorsal syndesmotic and the medial deltoid ligaments control ankle joint stability.

Ankle Injuries↗
PubMed1999

[Renal oncocytomatosis].

Multiple and bilateral oncocytomas are rare. There are only ten cases that have been previously described. Three of these displayed multiple and bilateral oncocytomas and microoncocytomas, a so-called oncocytomatosis. This report describes a case of renal oncocytomatosis found at autopsy. In addition, we found an adrenal adenoma, a pheochromocytoma and thoracic cicatrices 4 years after curatively resected large cell carcinoma of the lung. In the distal renal tubules we found oncocytic epithelial cells, with partial transition into microoncocytomas. Immunohistochemically, these and the main oncocytomas were CD 10 negative. These findings support the origin of oncocytoma from oncocytically transformed distal tubular epithelium. CGH analysis of the different tumors revealed no common cytogenetic changes. Coexistence of renal oncocytoma with other tumors is rare. Hitherto, coexistence of a renal oncocytomatosis with multiple tumors has not been described.

Adenoma↗
PubMed1999

[Decisions and attitudes in treatment of incompetent, chronically ill, aged patients. A comparison between nurses and physicians: why does no one ask the nurse?].

Health care decision making in incompetent severely ill patients presents many difficult medical, ethical, and legal problems for the physician. At the same time nurses represent the group of medical professionals who have the closest contact with the patient and who have to carry out most of the decisions and instructions. Treatment decisions and their determinants have been assessed by means of a questionnaire based on three case scenarios offering three different levels of available information of the patient's wishes (no information, DNR-order, advance directive). Responses of 191 doctors and 182 nurses have been analyzed. In both groups ethical factors and patient wishes were regarded as the most important. With an increasing level of information about the patient's will the compliance increased in both groups, being more pronounced among the nurses. The more important the will of the patient was estimated, the less difficult were the decisions, the less aggressive was the treatment level chosen, the less frequent rescuscitation was made, and the more helpful the information on patient's will were experienced. These important relationships occurred mainly in the nurses. Furthermore, age and level of dementia were related with the decisions though with less importance. The more legal aspects were regarded the more aggressive treatment options were chosen. Hospital cost were less important and did not influence the decision making. The results indicate that a more frequent use of advance directives would foster patient autonomy and at the same time lessen the burden on the medical staff. A comprehensive education of both the medical professions and the general public seems warranted.

Adolescent↗
PubMed1999

Evaluation of the clonal relationship between primary and metastatic renal cell carcinoma by comparative genomic hybridization.

The outcome of patients with renal cell carcinoma is limited by the development of metastasis after nephrectomy. To evaluate the genetic basis underlying metastatic progression of human renal cell carcinoma in vivo, we performed a comparative genomic hybridization analysis in 32 clear-cell renal-cell carcinoma metastases. The most common losses involved chromosomes 3p (25%), 4q (28%), 6q (28%), 8p (31%), and 9p (47%). The most common gains were detected at 17q (31%) and Xq (28%). There was one high-level gene amplification at chromosome 11q22-23. The mean number of aberrations in lymph node (4.8 +/- 2.8) and lung metastases (6.2 +/- 4.0) was lower than in other hematogenous metastases (11.5 +/- 8.7, P < 0.05), suggesting that hematogenous dissemination is linked to an acquisition of complex genomic alterations. As genetic differences between primary tumors and metastases give information on genetic changes that have contributed to the metastatic process, relative DNA sequence copy number changes in 19 matched tumor pairs were compared. Genomic changes, which frequently occurred in metastases but not in the corresponding primary tumor were losses of 8p and 9p and gains of 17q and Xq. An abnormal function of genes in these regions may contribute to the metastatic process. According to a statistical analysis of shared genetic changes in matched tumor pairs, a high probability of a common clonal progenitor was found in 11 of 19 patients (58%). Six metastases (32%) were genetically almost completely different from the primary, suggesting that detection of genomic alterations in primary tumors gives only a restricted view of the biological properties of metastatic renal cell carcinoma.

Carcinoma, Renal Cell↗
PubMed1999

Genetic differences in endocrine pancreatic tumor subtypes detected by comparative genomic hybridization.

The molecular pathogenesis as well as histogenesis of endocrine pancreatic tumors (EPTs) is not well understood, and the clinical behavior of EPTs is difficult to predict using current morphological criteria. Thus, more accurate markers of risk and better understanding of tumor initiation and progression are needed to allow a precise classification of EPTs. We have studied 44 benign and malignant EPTs by comparative genomic hybridization to correlate the overall number of genetic alterations with clinical and histopathological parameters and to identify chromosomal regions which might harbor genes involved in EPT pathogenesis and progression. Aberrations were found in 36 EPTs, and chromosomal losses (mean, 5.3) were slightly more frequent than gains (mean, 4. 6). The most frequent losses involved Y (45% of male EPTs), 6q (39%), 11q (36%), 3p, 3q, 11p (each 30%), 6p (27%), and 10q and Xq (each 25%), whereas most common gains included 7q (43%), 17q (41%), 5q and 14q (each 32%), 7p, 9q, 17p, 20q (each 27%), and 12q and Xp (each 25%). A correlation was found between the total number of genetic changes per tumor and both tumor size and disease stage. In particular, losses of 3p and 6 and gains of 14q and Xq were found to be associated with metastatic disease. Furthermore, characteristic patterns of genetic changes were found in the various EPT subtypes, eg, 6q loss in malignant insulinomas, indicating that these groups might evolve along genetically different pathways. The highlighted genetic aberrations, including the newly found involvement of 6q losses and sex chromosome alterations, should stimulate the further analysis of these chromosomal regions, which may lead to the discovery of novel genes important in the tumorigenesis and evolution of EPTs.

Chromosome Aberrations↗
PubMed1999

The compliance of doctors and nurses with do-not-resuscitate orders in Germany and Sweden.

A questionnaire based on a case-scenario offering three levels of available information about the patients' wishes was circulated with the objective to evaluate compliance with do-not-resuscitate orders (DNR) and advance directives (AD) from a cross-cultural perspective. Replies from 191 doctors and 182 nurses from Germany and 104 doctors and 122 nurses from Sweden were studied. The frequency of cardiopulmonary resuscitation (CPR) performed against the patients wishes varied between 32.5% (German doctors for DNR-scenario) and 8.3% (Swedish nurses for AD-scenario). The variance regarding the CPR decision could be explained by the help obtained by increasing information regarding the patients wishes and preferred treatment options. Since compliance is related to detailed information given by the patient the use of DNRs and ADs should be encouraged to a larger extent.

Adult↗
PubMed1999

Correction of peripheral lysosomal accumulation in mice with aspartylglucosaminuria by bone marrow transplantation.

OBJECTIVE: Bone marrow transplantation has been shown to alleviate symptoms outside the CNS in many lysosomal storage diseases depending on the type and stage of the disease, but the effect on neurological symptoms is variable or still unclear. Aspartylglucosaminuria (AGU) is a lysosomal storage disease characterized by mental retardation, recurrent infections in childhood, hepatosplenomegaly and coarse facial features. Vacuolized storage lysosomes are found in all tissues of patients and uncleaved enzyme substrate is excreted in the urine. The recently generated AGU mouse model closely mimicks the human disease and serves as a good model to study the efficiency of bone marrow transplantation in this disease. METHODS: Eight-week-old AGU mice were lethally irradiated and transplanted with bone marrow from normal donors. The AGA enzyme activity was measured in the liver and the brain and the degree of correction of tissue pathology was analyzed by light and electron microscopy. Reverse bone marrow transplantation (AGU bone marrow to wild-type mice) was also performed. RESULTS: Six months after transplantation the AGA enzyme activity was 13% of normal in the liver, but only 3% in the brain. Tissue pathology was reversed in the liver and the spleen, but not in the brain and the kidney. The urinary excretion of enzyme substrate was diminished but still detectable. No storage vacuoles were found in the tissues after reverse transplantation, but subtle excretion of uncleaved substrate was detected in the urine. CONCLUSION: Liver and spleen pathology of AGU was corrected by bone marrow transplantation, but there was no effect on lysosomal accumulation in the CNS and in the kidneys.

Acetylglucosamine↗
PubMed1999

Combined use of prostacyclin and higher perfusate temperatures further enhances the superior lung preservation by Celsior solution in the isolated rat lung.

BACKGROUND: The poor tolerance of the lung to ischemia and reperfusion (IR) still represents one of the limitations in clinically successful lung transplantation. Modified Euro-Collins (EC) is routinely used in lung preservation, but alternative solutions have been developed for improvement of pulmonary preservation. Celsior is an extracellular solution that has significantly reduced the IR-induced pulmonary damage in animal studies. So far, no extensive experimental studies exist concerning the influence of Celsior on pulmonary gas exchange following IR. METHODS: In an extracorporeal rat lung model 10 lungs, each, were preserved with Celsior (CE) and Celsior/prostacyclin (CEPC, 6 microg/100 ml) at 4 degrees and 15 degrees C, each, and compared to low-potassium Euro-Collins (EC-40, 40 mmol/liter potassium). After 2 hours of ischemia lungs were reventilated and reperfused using a roller pump. Oxygenation in terms of oxygen partial tension in the left atrial effluent, pulmonary vascular resistance (PVR), peak inspiratory pressure, and wet/dry ratio were monitored for 50 minutes. Furthermore, edema formation was evaluated by light microscopy. Statistical analysis was performed using ANOVA models. RESULTS: Compared to the EC-40 group, oxygenation was increased and amount of edema was reduced in most Celsior-preserved organs (p<0.032) with exception of the CEPC group at 4 degrees C (p = 0.06). Additional application of prostacyclin did not have any significant effect on oxygenation in the Celsior group. However, after temperature elevation of the CEPC perfusate to 15 degrees C, a superior partial tension of oxygen was observed (p<0.023) in contrast to the 4 degrees C groups CE and CEPC. The lowest PVR was found in the CE 4 degrees C group (p<0.02). CONCLUSIONS: Celsior provides better lung preservation than EC-40 solution. Application of prostacyclin at higher perfusate temperatures results in additional functional improvement. In vivo experiments and ultrastructural analysis are warranted for further evaluation of Celsior in lung preservation.

Animals↗
PubMed1999

Physicians' decision-making in incompetent elderly patients: a comparative study between Austria, Germany (East, West), and Sweden.

In order to investigate to what extent various determinants in the decision-making process for the treatment of severely ill incompetent patients are influenced by cultural and sociopolitical factors, 540 physicians in Austria, Germany (East and West), and Sweden, countries representing different healthcare systems, were surveyed using a self-administered questionnaire. It provided three case vignettes with different levels of information about the patient's treatment wishes in case of incompetence in a life-threatening situation. We found a general trend to a lower level of treatment in line with the patient's wishes when the information provided was more detailed. Remarkably, a substantial number of doctors did not comply with the patient's wishes. Ethical concerns and patient's wishes appeared as the most important factors whereas religious beliefs of the physician and hospital costs scored lowest. Because of the variability of treatment decisions and the importance of various factors determining the decision-making, an advance directive may be a feasible way of reducing the number of conflicts in critical situations. We recommend that ethical issues of clinical practice should be emphasized in the medical curriculum and in the training of physicians.

Adult↗
PubMed1999

The clam 3' UTR masking element-binding protein p82 is a member of the CPEB family.

During early development gene expression is controlled principally at the translational level. Oocytes of the surf clam Spisula solidissima contain large stockpiles of maternal mRNAs that are translationally dormant or masked until meiotic maturation. Activation of the oocyte by fertilization leads to translational activation of the abundant cyclin and ribonucleotide reductase mRNAs at a time when they undergo cytoplasmic polyadenylation. In vitro unmasking assays have defined U-rich regions located approximately centrally in the 3' UTRs of these mRNAs as translational masking elements. A clam oocyte protein of 82 kDa, p82, which selectively binds the masking elements, has been proposed to act as a translational repressor. Importantly, mRNA-specific unmasking in vitro occurs in the absence of poly(A) extension. Here we show that clam p82 is related to Xenopus CPEB, an RNA-binding protein that interacts with the U-rich cytoplasmic polyadenylation elements (CPEs) of maternal mRNAs and promotes their polyadenylation. Cloned clam p82/CPEB shows extensive homology to Xenopus CPEB and related polypeptides from mouse, goldfish, Drosophila and Caenorhabditis elegans, particularly in their RNA-binding C-terminal halves. Two short N-terminal islands of sequence, of unknown function, are common to vertebrate CPEBs and clam p82. p82 undergoes rapid phosphorylation either directly or indirectly by cdc2 kinase after fertilization in meiotically maturing clam oocytes, prior to its degradation during the first cell cleavage. Phosphorylation precedes and, according to inhibitor studies, may be required for translational activation of maternal mRNA. These data suggest that clam p82 may be a functional homolog of Xenopus CPEB.

3' Untranslated Regions↗
PubMed1999

[Decisions and attitudes of nurses caring for severely ill elderly patients: a culture-comparing study].

Results of a comparative investigation in Swedish and German nurses are presented. Based on a case-vignette with three levels of available information about patient wishes the subjects were asked about their decisions. Generally, the Swedish nurses showed a tendency towards less aggressive treatment-options and to perform less frequent cardio-pulmonary resuscitation (CPR) against the patient written will compared with the Germans. The compliance with patient wishes among nurses from both countries was related with the valuation of the patient directive as a useful tool in their decision-making process. Furthermore, the "level of dementia" emerged as a significant predictor of the treatment decision in both groups. The results point to the necessity of continuous education and training of nurses aiming at the issues of ethical attitudes and coping with ethically problematic situations in the treatment of the elderly in order to improve patient autonomy.

Aged↗
PubMed1999

Double-blind comparison of lansoprazole 15 mg, lansoprazole 30 mg and placebo as maintenance therapy in patients with healed duodenal ulcers resistant to H2-receptor antagonists.

BACKGROUND: Maintenance antisecretory therapy is often used to prevent duodenal ulcer recurrence and control symptoms. This study compared the efficacy and safety of lansoprazole 15 mg and 30 mg daily with placebo in preventing ulcer recurrence in patients with a recent history of duodenal ulcer disease. METHODS: Fifty-six patients were treated with either lansoprazole 15 mg, 30 mg or placebo o.m. RESULTS: Within 1 month of study initiation, 27% (four out of 15) of placebo-treated patients experienced ulcer recurrence as compared to 13% (two out of 15) and 6% (one out of 18) of lansoprazole 15 mg and 30 mg treated patients, respectively. Median time to first ulcer recurrence was > 12 months in lansoprazole patients. At Month 12, significantly (P < 0.001) more lansoprazole 15 mg patients (70%) and lansoprazole 30 mg patients (85%) remained healed. Eighty-two per cent of lansoprazole 15 mg and 76% of lansoprazole 30 mg patients remained asymptomatic during the entire study period. All placebo patients became symptomatic, experienced ulcer recurrence, or withdrew from the study by month six. The incidence of adverse events was comparable among the three treatment groups. CONCLUSIONS: Lansoprazole safely and effectively reduces duodenal ulcer recurrence and ulcer-related symptoms.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Fascioliasis: sonographic abnormalities of the biliary tract and evolution after treatment with triclabendazole.

Diagnosis of infection with the liver fluke Fasciola hepatica is usually difficult. Ultrasonography (US) might be a useful diagnostic alternative, and we assessed the value of sequential US in the diagnosis and monitoring of fascioliasis in 76 patients at baseline and for 60 days after treatment with triclabendazole. At baseline, biliary abnormalities were observed in 52 patients. Crescent-shaped parasites were seen in 11 patients; in 2 cases parasites were spontaneously moving and in 4 patients parasites were motionless. Postprandial examination revealed parasites adhering to the gallbladder wall in a further 5 cases. In 3 further cases, gallbladder contents were mobile but did not sediment downwards after patients changed position. Non-specific abnormalities were: impaired gallbladder contractility (n = 23), gallbladder tenderness (n = 19), debris (n = 6), calculi (n = 5), wall thickening (n = 2) and bile duct dilatation (n = 12). During day 1-7, Fasciola-like crescents in the gallbladder or passing through the bile duct were detected in another 15 patients, impaired gallbladder contractility in 16, gallbladder tenderness in 16, and bile duct dilatation in an additional 28 patients. Thirty-two patients with these US abnormalities experienced colic-like abdominal pain accompanied by increased alkaline phosphatase in 25 cases. During day 30-60, abnormalities regressed completely in 45 patients; 2/6 triclabendazole failures were evident by detection of living parasites. Biliary tract abnormalities are frequently observed by US, but the detection-rate of Fasciola hepatica is disappointingly low despite the parasite's relatively large size. US findings must therefore be interpreted together with other clinical measurements. The visualization of parasites being expelled through the dilated common bile duct allowed the causal interpretation of post-therapeutic abdominal pain and increase of liver enzymes. When triclabendazole is given on suspicion, visualization of worm expulsion and bile duct dilatation by US may be used to confirm diagnosis.

Adolescent↗