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Biomedical subjects

J Richter

Publications and source records attributed to J Richter.

At least 127 records · Page 7Linked to original sources

Stereological estimation of the volume weighted mean volumes of alveoli and acinar pathways in the rat lung to characterise alterations after ischaemia/reperfusion.

The aim of this study was to characterise pulmonary reimplantation injury in isolated, perfused rat lungs following 2 h of cold ischaemia, and 50 min. of in vitro reperfusion. The effects of 2 differently composed lung preservation solutions (low potassium Euro-Collins and Celsior; each n = 5) were examined in comparison with untreated, nonischaemic control lungs (n = 3). After fixation by vascular perfusion and tissue collection by systematic random sampling, the volume weighted mean volume (Vv) of alveoli and acinar pathways was estimated by light microscopic stereology using the method of point sampled intercepts in plastic embedded, Azan-stained material. Significantly higher Vv of alveoli and acinar paths was found in the Celsior group than in Euro-Collins preserved lungs. However, in the controls the size of acinar pathways was similar to Celsior preserved lungs whereas alveolar size was comparable to preservation with Euro-Collins. The between-animal coefficient of variation of alveoli was very low in controls and Celsior preserved but higher in the Euro-Collins group. Size distribution of alveoli and acinar paths in 15 size classes was largely homogeneous in all groups tested. In the Euro-Collins group the fractions of both class 1-alveoli and class 1-acinar paths significantly exceeded those of the other groups. Widely expanded alveoli (size classes 13-15) only occurred after preservation with Celsior whereas wider acinar paths (size class 15) were found in the Celsior group and in the controls. It is concluded that lung preservation with low-potassium Euro-Collins and Celsior solutions may act differently on distinct spaces in the distal gas-exchange regions of lungs. This may be due to selective effects on pulmonary surfactant activity and on elastic tissue elements in the alveolar ducts, respectively. Additionally, the method of point sampled intercepts is considered to be an efficient tool to evaluate the effects of different preservation solutions on lung parenchyma.

Animals↗

Structural protection of the myocardial capillary endothelium by different forms of cardiac arrest and subsequent global ischemia at 5 degrees C.

BACKGROUND: In transplantation surgery sufficient myocardial protection achieved by cardioplegic cardiac arrest and deep hypothermia is a prerequisite for successful resumption of donor heart function. Intraischemic damage of the endothelium combined with capillary compression may lead to the "no-reflow phenomenon" during reperfusion, resulting in insufficient cardiac resuscibility. METHODS: We evaluated the endothelial ultrastructure after various common forms of cardiac arrest and subsequent ischemia in deep hypothermia. Canine hearts were arrested by aortic cross clamping and surface cooling with Tutofusin' (ACC) or by coronary perfusion with Custodiol (histidine tryptophane ketoglutarate, HTK solution), with University of Wisconsin solution (UW), or with St. Thomas' Hospital solution. After extirpation the hearts were incubated at 5 degrees C in the solution used for cardiac arrest. Myocardial samples were taken immediately after cardiac arrest and after 2h, 4h, 6h, and 10 h of global ischemia. The degree of structural damage was evaluated by a scoring system. Endothelial swelling was determined as the mean barrier thickness of the capillary endothelium. RESULTS: At all selected time points our results show that 1) after cardioplegia with St. Thomas' solution, the degree of endothelial cell swelling was higher than after aortic cross clamping; 2) using HTK or UW solution, the endothelial ultrastructure was better preserved than after aortic cross clamping or using St. Thomas' solution, whereby HTK was slightly better than UW; 3) using UW solution, endothelial cell swelling was a little (up to 10%) but significantly less than after HTK perfusion. CONCLUSIONS: With respect to the intraischemic structural preservation of endothelial cells, UW or HTK solution combined with deep hypothermia promises adequate protection, compared with other clinically used methods tested.

Animals↗

Compliance curves during peritoneal dialysate infusion are like a distensible tube and are similar at multiple UGI sites.

OBJECTIVE: Disorders from increased intraabdominal pressure (IAP) result from filling the abdominal cavity beyond its capacity. The aims of this study were 1) to examine pressure:volume curves as fluid is infused into the intraabdominal cavity, and 2) to ascertain the best UGI site for indirect IAP measurements. METHODS: Chronic ambulatory peritoneal dialysis patients were studied (n = 4) supine. On day 1, manometry catheters measured IAP indirectly (intragastric and intrarectal) and intraesophageal (three sites) pressure. On day 2, antral-duodenal-jejunal manometry was performed to compare indirectly measured IAP at multiple sites. On both days, dialysate was infused at 200 ml/min until IAP was > or = 15 mm Hg or patient experienced severe discomfort. RESULTS: Filling had three phases: 1) an initial small increase in IAP as infusion began; 2) minimal further increase in IAP during infusion to about 3 L concurrent with a progressive increase in abdominal girth and mild abdominal discomfort; and 3) a linear increase in IAP with infusion > 3 L concurrent with intense abdominal discomfort and little increase in abdominal girth. During study day 2, intragastric, intraduodenal, and intrajejunal pressures were usually similar. CONCLUSIONS: The compliance curve of the abdomen with filling is similar to that of the bladder and large veins. Compliance curves with provocative meals may be useful in evaluating postprandial abdominal pain, dyspepsia, and bloating.

Abdomen↗

Relationships between various attitudes towards self-determination in health care with special reference to an advance directive.

OBJECTIVES: The subject of patient self-determination in health care has gained broad interest because of the increasing number of incompetent patients. In an attempt to solve the problems related to doctors' decision making in such circumstances, advance directives have been developed. The purpose of this study was to examine relationships between public attitudes towards patient autonomy and advance directives. SUBJECTS AND MAIN OUTCOME MEASURES: A stratified random sample of 600 adults in northern Sweden was surveyed by a questionnaire with a response rate of 78.2%. The subjects were asked about their wish for control of their health care, their concerns about health care, their treatment preferences in a life-threatening situation (both reversible and irreversible), and their attitudes towards the application of advance directives. RESULTS: Numerous relationships between various aspects of self-determination in health care (desire for control, fears of over-treatment, and choice of treatment level) in general and advance directives, in particular, were found. Those who wanted to have a say in their health care (about 94%) also mainly supported the use of an advance directive. CONCLUSIONS: The fact that almost 30% of the respondents were undecided concerning their personal use of advance directives points to a lack of knowledge and to the necessity of education of the public on these issues.

Adult↗

Ultrastructural alterations in intraalveolar surfactant subtypes after experimental ischemia and reperfusion.

Ischemia and reperfusion (I/R) result in surfactant dysfunction. Whether the impairment of surfactant is a consequence or a cause of intraalveolar edema formation is still unknown. The cumulative effects of lung perfusion, ischemic storage, and subsequent reperfusion on surfactant ultrastructure and pulmonary function were studied in a rat isolated perfused lung model. The left lungs were fixed for electron microscopy by vascular perfusion either immediately after excision (control; n = 5) or after perfusion with modified Euro-Collins solution (EC), storage for 2 h at 4 degrees C in EC, and reperfusion for 40 min (n = 5). A stereological approach was chosen to discriminate between intraalveolar surfactant subtypes of edematous regions and regions free of edema. Intraalveolar edema seen after I/R in the EC group occupied 36 +/- 6% (mean +/- SEM) of the gas exchange region as compared with control lungs (1 +/- 1%; p = 0.008). Relative intraalveolar surfactant composition showed a decrease in surface active tubular myelin (3 +/- 1 versus 12 +/- 0%; p = 0.008) and an increase in inactive unilamellar forms (83 +/- 2 versus 64 +/- 5%; p = 0.008) in the EC group. These changes occurred both in edematous (tubular myelin, 3 +/- 1%; unilamellar forms, 88 +/- 6%) and in nonedematous regions (tubular myelin, 4 +/- 3%; unilamellar forms, 77 +/- 5%). The ultrastructural changes in surfactant were associated with an increase in peak inspiratory pressure during reperfusion. In conclusion, surfactant alterations seen after I/R are not directly related to the presence of edema fluid in the alveoli. Disturbances in intraalveolar surfactant after I/R are not merely the result of inactivation due to plasma protein leakage but may instead be responsible for an increased permeability of the blood-air barrier, resulting in a vicious cycle of intraalveolar edema formation and progressing surfactant impairment.

Animals↗

Relation between concentration of lead, zinc and lysozyme in placentas of women with intrauterine foetal growth retardation.

Intrauterine foetal growth retardation (IUGR) implies increased risk of morbidity and mortality of the newborn. Aetiology of intrauterine retardation is probably multifactorial and may include maternal infection, malnutrition, placental dysfunction, hypertension, toxaemia, smoking, professional and environmental exposure. The work concentrates on the lead, zinc and lysozyme levels in blood and placental tissues of 50 females in the IUGR group and 43 females from a control group. Statistically significant differences in zinc and lead levels between the compared group were found. The IUGR group had lower zinc and higher lead levels. A significant negative correlation of zinc and lead levels was observed. We found a statistically significant relationship between lead levels in placental tissues and the age of the pregnant women. Higher age is associated with higher lead levels in placental tissue, whereas zinc levels decrease. In placental tissues of pregnant females of the IUGR group higher lysozyme levels were found. On the basis of the discussed results the authors recommend zinc supplementation during the pregnancy.

Adult↗

Do we know the cause of reflux disease?

Numerous factors are important in the pathophysiology of gastroesophageal reflux disease (GERD). The anti-reflux barrier consists of the lower esophageal sphincter (LES) and crural portion of the diaphragm. Absolute LES pressure less than 6 mmHg is required for gastroesophageal reflux (GER), but this is more frequently associated with increased episodes of transient relaxation than persistently low LES pressure. The vast majority of patients with complicated GERD have a hiatal hernia, because the gastric excursion into the chest displaces the LES segment of the distal esophagus above the crural diaphragm, promoting a pinch-cock effect that impairs acid clearance. Clearance of refluxed acid from the esophagus is dependent on gravity, peristalsis and saliva (pH > 6) to neutralize residual acid. Ineffective peristalsis, characterized by low amplitude contractions and dysmotility, represents the major impairment to normal acid clearance. Despite our great attention to these areas, gastric factors may be the most amenable abnormalities to treatment in GERD. Delayed gastric emptying is present in 10-15% of GERD patients, but more subtle postprandial abnormalities may contribute to gastric distension and transient LES relaxation. Although reflux patients are infrequently hypersecretors of acid, studies find acid combined with pepsin to be the most injurious agents to the esophageal mucosa. Recent studies also show increased amounts of bile acids in the refluxate of GERD patients, especially those with Barrett's esophagus. The influence of gastric colonization by Helicobacter pylori is just now being understood. Exciting studies suggest that H. pylori colonization, especially with the more virulent cagA-positive strains, may be protective against severe esophagitis and Barrett's esophagus. Increased intragastric ammonia production and pangastritis with gastric atrophy and intestinal metaplasia, both promoting hypoacidity, are the most likely mechanisms. Conversely, eradication of H. pylori may aggravate GER in some susceptible subjects.

Esophagogastric Junction↗

[Correlations between brain SPECT and neuropsychology assessments in mild and moderate stages of Alzheimer's disease].

UNLABELLED: Thirty-four patients with a probable Alzheimer's Disease (AD) (mild AD = 16; moderate AD = 18) and 12 matched controls were evaluated using semiquantitative SPECT-99mTc-HMPAO and neuropsychological tests (CERAD). RESULTS: Both temporal hypoperfusion (p < 0.01) and memory tests (p < 0.001) made it possible to differentiate the controls from mild AD patients. In these patients, significant correlations (p < 0.05) were also found between: 1) delayed recall test/temporal hypoperfusion, 2) learning memory test/temporoparietal and frontal hypoperfusion and 3) visual constructive praxis/posterior temporal hypoperfusion. In contrast to mild AD, moderate AD patients showed higher temporal (p < 0.01) parietal and frontal (p < 0.05) hypoperfusion along with worsening of praxis (p < 0.001) and memory tests (p < 0.05). CONCLUSIONS: SPECT imaging and neuropsychology evaluation can distinguish controls from AD patients with mild an moderate grades of dementia, showing a strong correlation from the early stages of AD.

Aged↗

[Use of a cyclotron in the production of positron emitting radionuclides].

The experience acquired by our center during the first two years of using cyclotron 18/9 (IBA) dedicated to the production of clinical positron emission radionuclides is described. The cyclotron performance characteristics, production yields, quality control and synthesized radiotracers are analyzed. Cyclotron makes it possible to produce up to 3,300 mCi of 18F-, 270 mCi of 18F2, 3,100 mCi of 11C, 502 mCi of 13N (in 120, 60, 35 and 20 minutes respectively) and 540 mCi/min of 15O. In our center, about 85% of the PET studies are performed with 18F-FDG, whereas the remaining are done with 15O-water, 11C-bicarbonate, 11C-methionine, 13N-ammonia or 18F-. Cyclotron is included in the Radiopharmacy Unit of our PET facility and is subjected to a global quality control program. Follow-up of the bombardment parameters and periodic verifications of the cyclotron performance have made it possible to prevent equipment functioning problems, increase mean time between stoppage and decrease downtime. We conclude that cyclotron has high production capabilities and allows enough flexibility for a clinical and research positron emission tomography center; furthermore, it can also be used for regional distribution of 18F-FDG to satellite PET centers.

Carbon Radioisotopes↗

[Analysis of kidney tumors in trichloroethylene exposed workers by comparative genomic hybridization and DNA sequence analysis].

Environmental and occupational mutagens such as chemical agents are suspected to be involved in cancer development. However, a direct link between carcinogen exposure and genetic alterations has been established only in a few examples. Carcinogen involvement in renal cell carcinoma (RCC) was recently supported by reports of an increased frequency of RCC among workers exposed to Trichloroethylene (TRI) in Germany. The aim of this study was to evaluate the phenotype and the genotype of renal tumors in occupationally TRI-exposed patients. Sporadic RCCs from TRI nonexposed patients served as control. Normal and renal tumor tissues from 12 patients with occupational histories of solvents and TRI exposure were histologically analyzed. Comparative Genomic Hybridization (CGH) was used to screen for genomic alterations along all chromosomal arms. Tumor DNA was analyzed for mutations of the von Hippel-Lindau gene (VHL) on 3p25.5 by PCR and sequencing analyses. The histological analysis revealed 9 clear cell (75%), 2 papillary RCC (18%) and 1 oncocytoma (8%). In clear cell RCC, DNA losses were frequently observed on 3p (66%), 6q (56%), 9p and 4q (44% each) and 2q (33%). DNA gains were detected on 9q, 17 (33% each) and 5q (22%). DNA gains were identified on chromosome 7 and 17 in papillary RCC. Four VHL gene mutations were found in three clear cell RCC (33%) with 3p loss. Comparisons of these results with data obtained from sporadic RCC revealed no unique phenotype, genotype or mutation pattern in the VHL gene of renal tumors after TRI exposure. Therefore, further studies on the relevance of dose and exposure time for the nephrocarcinogenic effect of TRI are indicated.

Base Sequence↗

The ontogeny of myostatin, follistatin and activin-B mRNA expression during chicken embryonic development.

The developmental pattern of myostatin, follistatin and activin-B genes in chick embryonic development was investigated. Total RNA was isolated from whole embryos on each of embryonic days (E) 0 to 6, from cranial halves of the embryo at E7 to 8, and from pectoralis muscle tissues at E9 to 20. Myostatin, follistatin and activin-B cDNAs were synthesized by reverse-transcription polymerase chain reaction (RT-PCR). Myostatin expression was first detected in embryos as early as the blastoderm stage (unincubated embryo, stage 1, E0). Myostatin mRNA concentration declined approximately 5 fold by E2 and remained lower through E6. Levels then increased 3 fold on E7 and plateaued through E16. Follistatin mRNA was first detected in the blastoderm stage of chick embryos. Overall follistatin mRNA increased 6 fold from E1 to E20 of development. Follistatin levels declined on E1 (approximately 2 fold) and remained low through E9. Follistatin mRNA reached the highest level prior to hatching. Activin-B mRNA from the whole embryo preparations (E0-E6) varied as the embryo matured. Overall activin-B gene expression from E11 to E20 appeared to decline (approximately 3.5 fold). This pattern is opposite of follistatin during the same period which is consistent with the opposing functions of these two proteins. We suggest that follistatin, activin-B and myostatin play an important role in embryogenesis and skeletal muscle development of the chick embryo. This study represents the first comprehensive report of myostatin mRNA patterns in chicken embryos.

Activins↗

[Immunomodulation in the treatment of atopic dermatitis].

In the submitted review the authors present information on possibilities of immunomodulating treatment of atopic dermatitis. Immunosuppressive treatment comprises systemic corticosteroid administration (possibly combined with cytostatic immunosuppressive preparations), cyclosporin A and phototherapy. Immunopotentiating treatment of AD makes use mainly of modulating preparations with the nature of physiological substances close to the immune system, substances obtained from natural biological sources (thymic hormones) or in recent years more frequently substances of recombinant origin (interferons, interleukins). The use of immunopotentiating drugs of chemical origin (synthetic substances) is used less frequently in AD. The use of intravenous immunoglobulin preparations for severe forms of atopic dermatitis is only just starting.

Adjuvants, Immunologic↗

Intratumoral heterogeneity of von Hippel-Lindau gene deletions in renal cell carcinoma detected by fluorescence in situ hybridization.

Although chromosome 3p deletions are considered an initial event in clear cell renal cell carcinoma (RCC), the reported prevalence of 3p deletions is highly variable. Because molecular analyses may be influenced by intratumoral heterogeneity, this study was performed to evaluate the genetic heterogeneity of the von Hippel-Lindau (VHL) gene (on 3p25.5) in RCC. Fifty-three clear cell and papillary RCCs were examined by dual-labeling fluorescence in situ hybridization with probes for the VHL gene and chromosome 3 centromere. The results were compared with histopathological phenotype, proliferative activity (Ki-67 labeling index) and 8p/17p deletions (both suggested to be linked to RCC progression). A clear-cut VHL deletion (in more than 40% of cells) was detectable in 69% of clear cell RCCs but was not detectable in nine papillary RCCs. A considerable genetic heterogeneity of VHL deletions was seen in clear cell RCCs including VHL-deleted subpopulations with different chromosome 3 counts within individual tumors as well as populations with and without VHL deletions. 8p22 and 17p13 deletions (each of which were detected in 18% of clear cell RCCs) were both linked to VHL deletions. However, 8p and 17p deletions were not associated with tumor grade, stage, or Ki-67 labeling index. The data indicate that some clear cell RCCs may develop independently of VHL alterations.

Carcinoma, Renal Cell↗

Expression and characterization of a Synechocystis PCC 6803 P-type ATPase in E. coli plasma membranes.

In a previous paper, we published the sequence of a P-type ATPase gene from Synechocystis 6803 [Geisler et al. (1993) J. Mol. Biol. 234, 1284] which showed significant homologies to eukaryotic calcium ATPases. To investigate the specificity and activities of this plasma membrane-bound enzyme, we expressed the slightly modified gene in an ATPase deficient E. coli strain. The expressed ATPase showed an apparent molecular mass of about 97kDa and is localized in the E. coli plasma membranes. The introduced 6xHis tag at the N-terminus allowed the purification of the Synechocystis 6xHis-ATPase by single-step affinity chromatography using a Ni2+-nitrilotriacetic acid resin. The ATPase activity of the enzyme is inhibited by vanadate (IC50 = 119 microM), N-ethylmaleimide, N,N-dicyclohexylcarbodiimide, and inhibitors of eukaryotic sarco(endo)plasmic reticulum Ca2+-ATPases; however, it is stimulated by thapsigargin. Formation of phosphorylated enzyme intermediates depends on calcium ions indicating that the Synechocystis P-ATPase acts as a calcium pump equivalent to eukaryotic sarco(endo)plasmic reticulum Ca2+-ATPases.

Adenosine Triphosphate↗

EGF-r gene copy number changes in renal cell carcinoma detected by fluorescence in situ hybridization.

Expression of epidermal growth factor receptor (EGF-r) is a frequent event in renal cell carcinoma (RCC). To investigate the role of EGF-r gene copy number changes related to EGF-r overexpression, 50 RCC specimens were examined by fluorescence in situ hybridization (FISH) and immunohistochemistry. Dual-labelling FISH with a repetitive pericentromeric probe for chromosome 7 and a probe for the EGF-r gene (at 7p13) was performed to analyse the EGF-r copy number in relation to chromosome 7 copy number on a cell-by-cell basis. Polysomy 7 was frequent in all histological types of RCC. Chromosome 7 polysomy was found in 26 of 35 clear cell (74 per cent), nine of nine papillary, and three of three chromophobe RCCs. EGF-r gene copy number was closely associated with the chromosome 7 copy number on a cell-by-cell basis. No EGF-r gene amplifications were found. EGF-r positivity was found in 37 of 50 cases (74 per cent) by immunohistochemistry. EGF-r positivity was more common in clear cell (81 per cent) than in papillary tumours (40 per cent; P = 0.029). Neither chromosome 7 nor EGF-r gene copy number was associated with EGF-r expression, indicating that an increased gene dosage is not a mechanism of EGF-r overexpression in RCC.

Carcinoma, Renal Cell↗

Comparative genomic hybridization reveals frequent chromosome 13q and 4q losses in renal carcinomas with sarcomatoid transformation.

Renal cell carcinomas (RCCs) with sarcomatoid transformation show the most malignant behaviour of all renal carcinoma types. In this study, comparative genomic hybridization was used to screen for losses and gains of DNA sequences along all chromosome arms in 12 sarcomatoid (S) RCCs. On average, there were 8.6 aberrations per tumour. DNA sequence losses (5.2 +/- 4.4) were slightly more frequent than gains (3.4 +/- 2.6). DNA gains most often involved chromosomes 17 (33 per cent), 7, and 8q (25 per cent each). High-level co-amplification involving 11q22-23 and 7p21-22 in one SRCC was not present in adjacent non-sarcomatous tumour areas, raising the possibility of oncogene involvement at these loci for sarcomatoid transformation. DNA losses were most prevalent at 13q (75 per cent) and 4q (50 per cent), suggesting that inactivation of tumour suppressor genes at chromosomes 13q and 4q may be linked to sarcomatoid growth of RCC. It is concluded that SRCCs are genetically highly complex. Chromosomes 13q, 4q, 7p21-22, and 11q22-23 may carry genes with relevance for sarcomatoid growth in RCC.

Adult↗

Voice-activated retrieval of mammography reference images.

We undertook this project to integrate context sensitive computer-based educational and decision making aids into the film interpretation and reporting process, and to determine the clinical utility of this method as a guide for further system development. An image database of 347 digital mammography images was assembled and image features were coded. An interface was developed to a computerized speech recognition radiology reporting system which was modified to translate reported findings into database search terms. These observations were used to formulate database search strategies which not only retrieved similar cases from the image database, but also other cases that were related to the index case in different ways. The search results were organized into image sets intended to address common questions that arise during image interpretation. An evaluation of the clinical utility of this method was performed as a guide for further system development. We found that voice dictation of prototypical mammographic cases resulted in automatic retrieval of reference images. The retrieved images were organized into sets matching findings, diagnostic hypotheses, diagnosis, spectrum of findings or diagnoses, closest match to dictated case, or user specified parameters. Two mammographers graded the clinical utility of each form of system output. We concluded that case specific and problem specific image sets may be automatically generated from spoken case dictation. A potentially large number of retrieved images may be divided into subsets which anticipate common clinical problems. This automatic method of context sensitive image retrieval may provide a "continuous" form of education integrated into routine case interpretation.

Breast Neoplasms↗

[Functional outcome of surgical therapy of talus fractures].

Forty-five patients with fractures of the talus were treated operatively at the Department of Surgery in Bergmannsheil Hospital between 1989 and 1995. Of these, 21 patients were operated on the day of the accident. The Marti/Weber classification system was used: 9 fractures were type I, 12 type II, 18 type III and 6 type IV. Twenty-five neck-fractures were classified according to Hawkins (type I-6, type II-10, type III-6, type IV-3). The mean time of follow-up was 37.3 months (minimum of 12 months). One patient needed a primary and 2 other patients a secondary arthrodesis of the ankle and subtalar joint; 2 others required arthrodesis of the talonavicular joint. Eleven patients showed no complaints at follow-up. Twenty-five reported complaints only during strenuous exercise, 5 others during walking and 3 patients reported initial pain when walking. The mean time of therapy was 22.5 weeks. As a consequence of trauma, 7 patients changed their jobs. The most important prerequisites for successful surgery are early reduction and stable osteosynthesis. Residual complaints are frequently seen. The rate of avascular necrosis (8% in fractures of the neck of the talus) and the necessity for arthrodesis was significantly diminished.

Adolescent↗