[Differential diagnosis of anemia. Clinical symptoms have little diagnostic value; MMW-Seminar on anemias, 1].
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Biomedical subjects
Publications and source records attributed to R Schaefer.
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The application of turbidimetric homogeneous immunoassays made the determination of several plasma components widely available. The sensitivity and accuracy of these assays are appropriate enough for routine laboratory use; however, in the case of many pathologically high concentration samples, prozone effect (high dose hook effect) can be observed, that leads to false-negative determination. Up to the present there are no cost-effective algorithms available for the safe detection of the prozone effect. Pathological serum ferritin values can be elevated up to 5000 ng/ml, while the measuring range covers only the 0-440 ng/ml range by a commercial assay. The determination of samples with ferritin concentration higher than 1500 ng/ml results in false-negative values because of the overlapping measuring range and prozone effect range. The prozone effect can be recognised by analysis of reaction kinetics after measurement. We have developed a neural network classifier system to analyse reaction kinetics of the measurements and check the prozone effect. One thousand five hundred determinations and 77 patient samples were used for neural network training and test. Using the trained neural networks, false-negative results can be filtered immediately after the determination, without re-run; thus, the sensitivity of plasma ferritin determination may become reliable enough, even in the case of high concentration samples. Applying this new technology, false-negative serum ferritin determinations can be avoided, thus even a relatively high hook effect rate (5-12% in different patient groups) can be handled safely.
We examined the effect of ondansetron, an antagonist of type 3 serotonin receptors, on the whole cell response of freshly isolated hippocampal CA1 pyramidal neurons of neonatal and "mature" rats to glycine using the gramicidin perforated patch technique. Ondansetron depressed the current induced by subsaturating concentrations of glycine (IGly) in a concentration-dependent manner. The ondansetron concentration needed to depress IGly induced by 30 microM glycine to half amplitude was 25 microM. Ondansetron (54 microM) shifted the glycine concentration-response curve to the right in a parallel manner, increasing the EC50 for glycine from 40 +/- 3 microM to 70 +/- 5 microM. Ondansetron increased the time constant of activation of IGly without affecting the time constant of deactivation. When examined under current clamp conditions, glycine induced depolarization and hyperpolarization in neonatal and mature neurons, respectively; ondansetron also suppressed these responses to glycine. The data suggest that ondansetron competitively inhibits the glycine receptor.
OBJECTIVE: This study aimed to sensitize the practitioner to the unusual presentation of basal cell carcinoma in a recurrent cholesteatoma mass. STUDY DESIGN: The study design was a case report format. SETTING: The study was conducted at a tertiary referral hospital. PATIENT: The patient studied was a contralaterally anacusic veteran. INTERVENTION: Interventions were excision of cholesteatoma and withholding of adjunctive radiation. CONCLUSION: Primary basal cell carcinoma may present in a revision cholesteatoma field.
The main aim of the research in medical diagnostics is to develop more exact, cost-effective and handsome systems, procedures and methods for supporting the clinicians. In their paper the authors introduce a new method that recently came into the focus referred to as artificial neural networks. Based on the literature of the past 5-6 years they give a brief review--highlighting the most important ones--showing the idea behind neural networks, what they are used for in the medical field. The definition, structure and operation of neural networks are discussed. In the application part they collect examples in order to give an insight in the neural network application research. It is emphasised that in the near future basically new diagnostic equipment can be developed based on this new technology in the field of ECG, EEG and macroscopic and microscopic image analysis systems.
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BACKGROUND: Nearly 50% of all cancer patients receive therapeutic radiation during the course of their disease. The risk of late complications is the main dose-limiting factor in the delivery of radiation therapy. The small intestine, the major site of chronic radiation enteropathy, is also the principal organ of glutamine consumption. We therefore hypothesized that the provision of supplemental glutamine may have a protective effect on the development of chronic radiation enteropathy. METHODS: This study evaluated the effects of supplemental oral glutamine on the development of chronic radiation (XRT) enteropathy. After scrotalization of a loop of small intestine, rats were randomized to receive 1 g/kg/day glutamine (GLN) or glycine (GLY) by gavage. After 2 days of prefeeding, rats were randomized to 1 of 4 groups: GLN + XRT (n = 10), GLY + XRT (n = 10), GLN only (n = 10), GLY only (n = 10). Twenty Gy was delivered to the scrotalized bowel in the GLN + XRT and GLY + XRT groups via a collimated beam. Gavage was continued for 10 days. Animals were then pair-fed chow. Rats were killed at 2 months postirradiation. Chronic radiation injury was assessed microscopically. RESULTS: Injury scores in GLN + XRT were similar to those of unirradiated bowel and significantly different from GLY + XRT (1.89 +/- 0.48 in XRT + GLN vs. 6.42 +/- 1.55 in the XRT + GLY, p < 0.01). Elevated Injury Scores in the XRT + GLY group correlated with gross thickening and fibrosis, a 10-fold decrease in gut GLN extraction (1.40 +/- 4.3% in GLY + XRT vs. 16.0 +/- 5.1% in GLN + XRT, p < 0.05), and a 30% decrease in glutathione content (2.46 +/- 0.19 and GLY + XRT vs. 3.17 +/- 0.17 GLN + XRT, p < 0.05). CONCLUSIONS: Provision of GLN during abdominal/pelvic XRT may prevent XRT injury and decrease the long-term complications of radiation enteropathy.
In our study, complications of oligohydramnios were examined. In medical records of all 5,210 deliveries of our department between 1987 and 1990 181 cases of oligohydramnios were identified. The diagnosis was confirmed by ultrasound and based on the method described by Mannings and Platt: amniotic fluid depots of less than 1 cm were defined as oligohydramnios. All 181 cases met the above definition, which results in an incidence of 3.5% pregnancies with reduced amniotic fluid. We examined the records of mother and foetus, the delivery and perinatal complications and follow-up of the newborn. In more than 60%, foetal asphyxia, breech position and other anomalies during delivery were followed by Cesarean section or vaginal operative delivery by forceps or vacuum extraction. In 30 cases, oligohydramnios was caused by premature rupture of membranes. In the other cases, the diagnosis based on maternal or foetal complications such as gestosis (n = 7), abruptio placentae (n = 10), foetal growth retardation (n = 47) and malformations or chromosomal anomalies. 89 newborn were transferred to a paediatric hospital immediately after delivery. Potter's syndrome was the main anticipated diagnosed malformation (n = 20). The lack of amniotic fluid was furthermore followed by a higher rate of pulmonary complications such as RDS and hypoplasia of the neonatal lung (n = 21). In conclusion, our study underlines the fact, that oligohydramnios must be regarded as an important reason of high risk pregnancy followed by many complications for foetus and newborn. The incidence of perinatal mortality in our examination was 7.2%. This rate is 10 fold higher than in the total number of deliveries of our department.
An overview on the properties, actions and localization of thrombomodulin (TM) in situations of tissue injury and in selected tumors is presented. The localization and activity of TM after injury to vascular endothelium shows that following balloon catheter denudation of the endothelium of the rabbit aorta, the activity and immunohistochemical staining is markedly reduced. The functional and antigenic levels approach the control levels approximately one week after the initial injury. The results suggest that the neointimal smooth muscle cells express TM. This phenotypic plasticity of the neointimal smooth muscle cells may be important in conferring thrombo-resistance to the lumenal lining cells of vessels after injury. Studies are also reviewed on the use of soluble recombinant TM to prevent thrombosis after ligature of vessels in an experimental model. Further characterization on the immunohistochemical distribution of TM in normal tissues and tumors shows that staining with a monoclonal anti TM antibody can be very useful in separating mesotheliomas from pulmonary adenocarcinomas. These studies may lead to insights concerning the role of TM in tissue-injury-repair and tissue differentiation.
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Thrombomodulin (TM) is a glycoprotein of molecular weight 75,000 kd that is normally present in restricted numbers of cells, including endothelial and mesothelial cells. In this study, the authors tested the possibility of using anti-TM to facilitate the diagnosis of mesothelioma. All of the 31 mesotheliomas and the two mesothelioma cell lines (MS-1 and MS-2) tested were stained positively with anti-TM. The specificity of anti-TM staining in mesothelioma cells was further confirmed by in situ hybridization of MS-1 cells with a TM-specific probe. The expression of TM in MS-1 cells was increased markedly when these cells were induced by 12-0-tetradecanyl phorbol 13-acetate (TPA) to differentiate. The expression of TM in mesothelioma cells, however, did not correlate with any particular phase of the cell cycle. In an attempt to differentiate pleural mesothelioma from pulmonary adenocarcinoma, the authors compared the expression of TM, carcinoembryonic antigen (CEA), and Leu M1 in these two types of tumors. Only four of 48 (8%) pulmonary adenocarcinomas were stained positively by antibodies to TM. Therefore, immunohistochemical staining with antibodies to TM yielded 100% sensitivity and 92% specificity for diagnosis of mesothelioma. All of the mesotheliomas stained negatively for CEA and Leu M1, except for one, which showed minimal focal positivity for Leu M1. In contrast, 79% and 60% of adenocarcinomas stained positively for CEA and Leu M1, respectively. These findings suggest that immunocytochemical staining with anti-TM should be added to the battery of tests to increase the diagnostic sensitivity and specificity for differentiating mesothelioma from pulmonary adenocarcinoma.
The clinical value of phospholipase measurements in serum is as yet an open question, particularly with respect to the prognosis quoad vitam. Sensitivities and specificities at different decision levels for unselected intensive care patients are reported and discussed.
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Cushing's group, operating on metastatic brain tumors in the 1920s, was the first to point out that lung cancer (usually adenocarcinoma in an upper lobe) was the most common primary tumor. Excision of a solitary metastasis could result in long-term survival. Magilligan and coworkers (J Thorac Cardiovasc Surg 1976;72:690) introduced the modern era of large series of combined lung-brain resection with low mortality (3%) and a 5-year outcome of 21%. Our results (92 patients) confirm their experience. Presenting symptoms were pulmonary (53), synchronous (28), or neurologic (11). Nonsquamous cell (48) predominated. Pulmonary resections (45) were pneumonectomy (five), lobectomy (27), segmentectomy (five), and wedge biopsy (eight). Craniotomy (68) and irradiation resulted in recurrence in seven patients. There was no operative mortality. The survival rate after curative lung and brain resection (27) was 52% at 1 year, 35% at 2 years, and 21% at 5 years. Median survival in noncurative combined resection (eight), craniotomy only (27), thoracotomy only (eight), or no surgery (22) groups, with or without irradiation or chemotherapy, averaged 6.4 months. Every effort should be made to give patients with this syndrome the benefit of combined surgery, which was not offered or agreed on in more than a third of our cases.
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We analyzed 384 veterans who had "curative" (sometimes conservative) resection from 1966 through 1986 for stage I, non-small-cell primary lung cancer to identify significant variables influencing survival. Operative mortality was 3.1%, mainly from heart attacks. Most patients were asymptomatic, presenting with other diseases of smoking. Five-year survival was 43%; deaths from lung cancer only, 63% (T1, 73%; T2, 49%). Two hundred fourteen (57.5%) of the 372 operative survivors had T1 and 158 (42.5%) had T2 disease. Sixty-five percent had peripheral nodules (84%, T1; 38% T2). Pure squamous cell predominated, in 63% overall (T1, 55%; T2, 74%). Systemic metastases caused most cancer deaths. Within T1, diameter was highly significant. Cell type and time of operation (before or after Dec 31, 1980) were also significant. Under T2, only scarring and differentiation were significant. Veterans in this group live longer if they have small squamous cell tumors.
The transformed phenotype of rat FE-8 cells transfected by an activated human HRAS gene was suppressed upon fusion with normal cells. An experimental approach was developed to identify and isolate a human gene capable of suppressing the transforming activity of the HRAS oncogene in FE-8 cells. Genomic DNA from human placenta was introduced into FE-8 cells by cotransfection with the plasmid pY3 conferring hygromycin B resistance. Transfectants were selected in medium containing hygromycin B. HRAS-transformed FE-8 cells showed an increased sensitivity toward ouabain when compared to their normal counterparts. Therefore, the population of transfected hygromycin B-resistant cells was treated with ouabain to eliminate cells with a transformed phenotype. Ouabain selection resulted in a small number of cell clones exhibiting a more normal phenotype. The clones had lost the morphology of transformed cells and required anchorage for growth. The tumorigenicity of transfectants in nude mice was reduced but not completely abolished. FE-8 revertants continued to express the p21 RAS protein. Human repetitive sequences contained in the DNA of a secondary transfectant were used for isolation of the suppressor gene from reverted FE-8 cells. The cloned DNA fragment was transfected into tumorigenic FE-8 cells and conferred a partial reversion of the transformed phenotype.