A monoclonal antibody against prothrombin fragment 1 behaves like a lupus anticoagulant.
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Biomedical subjects
Publications and source records attributed to M Kraus.
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BACKGROUND: Studies indicate that physicians are poorly prepared to identify and treat tobacco, alcohol, and drug use disorders. Several faculty development programs have been created to increase the number of residency teaching faculty with expertise in this area. There is limited information, however, on those who currently teach residents about these problems and whether there is a need for additional faculty development programs. METHODS: We conducted a 2-stage national survey of faculty who teach residents about substance use problems. First, residency directors from 7 specialties (family medicine, psychiatry, internal medicine, pediatrics, obstetrics and gynecology, emergency medicine, and osteopathy) responded to a mailed questionnaire asking them to identify faculty who teach residents about substance use disorders. Second, those identified were contacted and asked to participate in a telephone interview. RESULTS: Of 1293 faculty identified by the residency directors, 769 participated in a research interview. Most of these teachers were full-time physician faculty, men, white, and based in departments of family medicine or psychiatry. Teaching was primarily conducted in hospitals, general outpatient clinics, and classrooms rather than alcohol and drug treatment programs. Less than 10% of the faculty performed clinical work in alcohol and drug treatment programs, and only 19% were certified addiction specialists. The respondents reported a definite need for additional development programs for themselves and other residency teaching faculty. CONCLUSIONS: We suggest a modest increase in the number of faculty who teach residents about substance abuse disorders, and the creation of additional faculty development programs.
The ky mouse mutant exhibits a degenerative muscle disease resulting in chronic deformation of the spinal column. Following a previous report describing the mapping of the ky locus to a small region of mouse chromosome 9 (Skynner et al., 1995, Genomics 25, 207-213), we have now undertaken a positional cloning approach to identify candidate genes for ky. A YAC/BAC contig encompassing the ky locus was constructed comprising 48 YAC clones and 48 newly generated STSs. The results from the combined physical and genetic analyses showed that only two overlapping BAC clones, which together do not exceed 260 kb, span the ky nonrecombinant region. A combination of gene hunting methods on the critical BACs has led to the identification of seven coding fragments, which have been tested for expression. The expression analysis and the position of the coding fragments on the contig suggest their grouping in at least four transcription units. One of these transcription units is expressed exclusively in skeletal muscle, making it a suitable candidate for this muscle defect in the ky mouse.
OBJECTIVE: To determine whether ventricular late potentials, detected by means of signal-averaged electrocardiography (SAECG), were associated with sudden death in Doberman Pinschers with occult cardiomyopathy. DESIGN: Case series. ANIMALS: 39 Doberman Pinschers with occult cardiomyopathy. PROCEDURE: Cardiomyopathy was diagnosed by means of serial echocardiography and ambulatory electrocardiography; SAECG was performed 1 or more times for each dog. RESULTS: 12 dogs died suddenly; the other 27 died after developing overt clinical signs of congestive heart failure. Results of SAECG were associated with outcome, and dogs in which ventricular late potentials were detected were more likely to die suddenly. however, 5 dogs for which results of SAECG were normal (n = 2) or equivocal (3) also died suddenly. CLINICAL IMPLICATIONS: Results suggest that SAECG may be useful in predicting whether Doberman Pinschers with occult cardiomyopathy, confirmed on the basis of results of echocardiography, are at risk of dying suddenly. However, the possibility of sudden death cannot be ruled out simply because results of SAECG are normal.
Microsensors provide instruments particularly suited for the noninvasive analysis of cell and tissue cultures. The outstanding benefit lies in the passive behaviour of continuously working transducers, which in turn allows the dynamic recording of function-specific cellular processes. The microsensor system presented in this paper is a modular arrangement of various planar and non-planar sensor elements surrounding small cell culture chambers. An optic access to the cultures (e.g. for high resolution light microscopy and spectro-photometric techniques) enables a parallel and comparative data acquisition. The system was originally designed for biomedical research in chemotherapy and pharmacology but it proved to be an effective device both for toxicological and environmental research.
The diagnosis of the procoagulant system is routinely based on activated partial thromboplastin time (APTT) and PT results indicating only a bleeding tendency. Routine screening tests for thrombophilia providing an objective measure of the anticoagulant potential of the blood are still lacking. Only antithrombin is determined quite frequently. The recent findings of activated protein C (APC) resistance have demonstrated the importance of the PC anticoagulant system in inherited thrombophilia. A vast body of evidence from in vitro and animal experiments as well as from recent clinical studies is presented revealing that the PC system potential plays a major role in maintaining the hemostatic balance at a variety of clinical conditions. It is suggested that acquired defects in the PC system are an underestimated cause for clinically induced venous thrombosis. New screening assays for the PC system potential are presented, which already indicate quite well congenital as well as acquired interferences of the PC system potential.
BACKGROUND: Barrett's oesophagus is a premalignant condition. Recent reports have suggested that laser coagulation or photodynamic therapy combined with acid suppression may induce reconstitution of squamous mucosa. However, a high percentage of residual glands remain in cases treated with both techniques. Argon plasma coagulation (APC) appears to be an attractive alternative to other thermoablative techniques. The aim of this study was to investigate the reconstitution of squamous epithelium in Barrett's oesophagus after APC. METHODS: Fifteen patients with histologically proven Barrett's oesophagus were included in a prospective study. After base-line documentation by videotaping and biopsies, Barrett's epithelium was treated by repeated APC at intervals of 4-6 weeks until complete squamous restoration was achieved. All patients were kept under high-dose proton pump inhibitor therapy. RESULTS: In 13 patients complete reconstitution of squamous epithelium was achieved. Buried glands after squamous restoration were detected transiently in only one case after the first session. As side effects seven patients had mild retrosternal discomfort. One patient reported severe retrosternal pain for 1 week. He then refused further APC sessions. Another patient was excluded because of noncompliance. During the follow-up period (6-13 months) recurrence of Barrett's epithelium was observed in one patient. CONCLUSIONS: APC is a suitable technique for achieving squamous restoration in Barrett's oesophagus. The rare occurrence of remaining buried glands may result from the homogeneous coagulation achieved by the ionized argon gas beam.
Apolipoprotein E (apoE), a protein produced by glial cells, is responsible for maintenance of the structural integrity of the microtubules within the axon of the neuron. The gene associated with apolipoprotein E, APOE, influences the construction and regeneration of the microtubules in an APOE allele-specific manner: APOE 2/2 may be neuroprotective, whereas APOE 4/4 may be neurodestructive. Thus, APOE appears to be one genetic factor that modifies the brain's response to insult, and therefore may modify the severity of neuropsychologic deficits. This article presents an overview of the genetic relation between APOE and neuropsychological function in Alzheimer disease and proposes a relation between APOE and recovery after head injury.
Heparin-binding proteins (designated BHB-2-BHB-9) were isolated from boar seminal plasma by affinity chromatography on heparin immobilized on polyacrylamide gel, followed by reverse phase HPLC. According to their N-terminal amino acid sequences, BHB-3-BHB-5 belong to the AQN family of spermadhesins and BHB-7-BHB-9 to the AWN family. BHB-6 is composed of two different proteins. The dominant protein (14 kDa) has the N-terminal amino acid sequence HNKQEGRDHD that is identical to the sequence of human semenogelin at positions 85-94. The minor proteins (16 and 17 kDa) belong to the AWN family of spermadhesins. The 14 kDa HNK protein does not crossreact with antibodies against AQN or AWN spermadhesins. BHB-2 also binds to the acrosome of boar epididymal spermatozoa but has the N-terminal sequence DQH. Therefore, basic protein BHB-2 belongs to a new family of DQH sperm surface proteins that are homologous to the acidic proteins from bull and stallion seminal plasma, to the collagen binding domain II in fibronectin and to the leucocyte cell-cell adhesion regulator, but are not homologous to AQN or AWN spermadhesins. Nevertheless, anti-AQN-1 spermadhesin antibodies crossreact strongly with DQH protein. All boar heparin-binding proteins bind concanavalin A indicating their glycoprotein nature, which was proved by the detection of glucosamine and galactosamine residues in their molecules. Furthermore, spermadhesins interact with zona pellucida, protease inhibitors and a polyacrylamide derivative of heparin. Affinity chromatography experiments showed that the DQH protein bound to gelatin-agarose together with the AWN proteins and that the DQH protein and AQN-1 spermadhesin belong to the phosphoryl choline binding proteins.
Heparin-binding proteins BHB 2-BHB 5 were purified from boar seminal plasma by affinity chromatography on a heparin-polyacrylamide column and reversed phase HPLC. Three of the proteins, BHB 3-BHB 5, were found to be identical to spermadhesins AQN 1-AQN 3 isolated from boar spermatozoa. The lectin-like properties of the isolated proteins BHB 2-BHB 5 were studied using double-diffusion in agarose gel, enzyme-linked binding assay, and inhibition assays of erythroagglutinating activity. It was found that proteins BHB 3-BHB 5 (spermadhesins AQN 1-AQN 3) interacted with glycoproteins containing O-glycosidically bound oligosaccharide chains, but not with those containing only N-linked carbohydrate chains. The strongest interaction was observed between BHB 3 (AQN 1) and desialyzed bovine submaxillary gland mucin, the glycoprotein containing only O-glycosidically linked saccharides. No interaction of BHB 3-BHB 5 proteins with simple saccharides, their derivatives or acidic polysaccharides was observed. Both the hemagglutinating activity and saccharide-binding properties of BHB 2 protein were quite different. Agglutinating activity of human erythrocytes by BHB 2 protein was significantly higher than that by BHB 3-BHB 5 proteins (AQN spermadhesins). In contrast to AQN spermadhesins, BHB 2 protein (DQH sperm surface protein) interacted strongly with acidic polysaccharides and sialyzed glycoproteins, but no binding of desialyzed glycoproteins as well as N-acetyl-alpha-D-galactosaminyl-O-serine,simple monosaccharides and amino sugars was observed.
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BACKGROUND: Internal quality control of medical performance in the interest of patient safety is not a new idea. In fact it has been implemented in varying degrees since the beginnings of medicine. ACTUAL SITUATION AND METHODS: Ever since hospitals are compelled by law to apply methods of quality assurance and external quality control, the question arises as to whether this law can achieve a concrete increase in quality of patient care or whether it rather serves to support economically motivated goals of health care policies, in the sense of an increase in efficiency of performance by physicians. Seen in the light of the overall situation of hospital care, the attempt to create mandatory quality standards is problematical. A reduction of hospital beds and a decrease in the average length of hospital stay contrasts the growing number of treated patients. This presents a problem which must be compensated for, despite cutbacks in budget and personnel. Methods of quality analysis are of the implicit as well as of the explicit type. Implicit methods are based on retrospective data analysis lacking previously set standards of comparison. These methods harbor the danger of viewer-dependent subjectivity (restricted reliability). Explicit methods are based upon comparison to previously defined standards. These methods are more objective, but often fail to give consideration to individual situations (restricted validity). The infrastructure necessary in order to sensibly apply quality control in the hospitals is not yet present in Germany. The software required in order to record and analyse data is still in a stage of development in many places. CONCLUSION: It is of importance not to leave external quality control to politicians and economists unfamiliar with the subject matter, but rather that quality control is implemented by experts in the medical field.
Acidic microenvironmental conditions combined with large hypoxic areas are ubiquitous hallmarks of most solid tumors. They result from a poorly organized vascularization and a deviant energy metabolism. There is convincing evidence supporting the hypothesis that such physico-chemical conditions promote the microevolution of malignant cells, inhibit the cellular immune response, and favor tumor cell invasion. In agreement with published data, our cell biological analyses and computer simulations indicate that treatment schemes which restore a tumor microenvironment reflecting that one found in normal tissues might improve the efficiency of immunotherapies and classical methods for cancer treatment. We suggest that the tumor microenvironment could be effectively monitored and manipulated by means of silicon-based feedback bioactuators which are controlled by integrated microsensors. In principle, miniaturized bioactuators can be implanted directly at the sites of inoperable tumors and metastases where they function as a "pH clamp" and thereby can reconstitute normal physicochemical conditions. Drug application could be precisely controlled by an integrated microprocessor. Our paper summarizes the current state of development of microsensor-based feedback bioactuators and outlines possible applications in biophysical cancer treatment.
Allograft rejection is associated with complement activation. Yet inconsistent results were obtained in evaluating plasma levels of complement factors or activation products as rejection markers. Therefore the human anaphylatoxin C5a and the soluble terminal complement complex (TCC) were measured by daily enzyme immunoassays on plasma (P) and urine (U) samples from 28 patients undergoing renal transplantation over a mean postoperative period of 25.8 days. The complement levels were evaluated longitudinally (cutoff of 100% increase on the previous day's level) during periods of rejection, stable graft function, acute tubular necrosis, and cytomegalovirus disease. Regarding the detection of 13 acute rejection episodes, U-C5a showed a diagnostic accuracy of 81% (sensitivity of 85%, specificity of 77%), P-C5a one of 62%, and P-TCC one of only 30%. The U-C5a increment (mean rise of 379%) preceded the clinical diagnosis of rejection by an average of 1.6 days. Cytomegalovirus diseases (n = 4) were associated with high P-C5a levels (mean increase of 251% by the time of the first detection of viral DNA). In contrast, resumption of kidney function after acute tubular necrosis (n = 10 periods) was heralded by marked peaks of U-C5a (x = 43.7 microg/l). U-TCC was not detected in any clinical setting. In conclusion, as opposed to P-TCC, U-TCC, and P-C5a, the anaphylatoxin C5a, measured daily in urine, might have potential as an early and reliable marker for acute renal allograft rejection.
Solid tumors usually exhibit a poorly organized vascularization and a deviant energy metabolism which result in an acidic pH and large hypoxic areas in the tumor microenvironment. A lot of cell biological data support the hypothesis that such physico-chemical conditions are promoters of the microevolution of malignant cells, inhibitors of the immune response, and co-factors for tumor cell invasion. Our experimental in vitro analyses and computer simulations indicate that the efficiency of immunotherapies and classical methods for cancer treatment might be improved if a physico-chemical microenvironment could be restored which reflects that found in normal tissue. In order to monitor and manipulate the tumor microenvironment, we suggest utilizing silicon-based feedback bioactuators which are controlled by on-line microsensors. These miniaturized bioactuators play the role of 'pH clamps' and can be implanted directly at the sites of inoperable tumors and metastases where they can reconstitute normal physico-chemical conditions. The drug application scheme can be precisely controlled by an integrated microprocessor. The paper summarizes the current state of development of such microsensor-based feedback bioactuators and outlines their potential for biophysical cancer treatment.
As cutaneous pilar leiomyomas have received little attention in the recent literature, 53 lesions from 45 patients were studied to analyze their clinicopathologic features. There was an equal distribution between both sexes; most patients were adults with a wide age distribution. Both multiple (29 lesions from 21 patients) and solitary tumors (18 patients) were included. Lesions on the extremity (29 tumors) were common in both groups, whereas truncal tumors (11) were confined largely to patients with multiple lesions. In six patients the number of lesions was not specified. The tumors were painful in 17 patients. Three patients had a positive family history of similar lesions. Histologic study revealed ill-defined bundles of well-differentiated smooth muscle cells in the reticular dermis in all cases, although nine lesions had a more nodular pattern. Overlying epidermal hyperplasia was noted in 29 cases (54.7%). Immunohistochemically there appeared to be an increased number of nerve fibers within and surrounding the tumors. Mitotic activity was observed in 15 lesions (28.3%), 13 of which had <1 mitosis per 10 high power fields (HPF); the remaining two lesions had 1-2 mitoses per 10 HPF. Follow-up was available in 10 of these mitotically active tumors and ranged from 9 months to 7 years. There was no recurrence in any of them. We have concluded tentatively that leiomyomas of arrector pili origin may exhibit a low mitotic activity of <1 per 10 HPF and that this does not adversely affect the prognosis for these patients.
We noted a series of 12 consecutive patients with a DDD Genisis pacemaker that showed an unexpected and a relatively rapid fall in battery voltage and output as these devices approached end-of-life (EOL). Twenty-one of 24 leads were Vitatron Helifix leads and there was a relatively high mean threshold (atrial 2.5 +/- 0.94 V; ventricular 2.9 +/- 0.65 V). These devices were replaced after 65 +/- 12 months. During the 9.3 +/- 3.5 months before replacement, a striking fall in voltage from 2.7 +/- 0.04 V to 2.49 +/- 0.05 V was seen. Battery impedance rose from 3 +/- 1.2 K omega to 10.2 +/- 4.3 K omega during this same period. We unexpectedly observed a marked difference between programmed and telemetered output for both atrial (50%) and ventricular leads (30%). A discrepancy between measured and telemetered magnet rate was also seen. Despite this relatively rapid fall in battery voltage, several of these devices did not meet the manufacturer's recommended replacement time (RRT) criteria by magnet rate or according to the projected RRT determined by the relationship of battery impedance to current drain. These data have implications for the selection of RRT and EOL criteria for this device. Magnet rate measured by surface ECG was the safest indicator for RRT. Follow-up for this pulse generator should be increased to every 2 months when battery impedance is > 2 KOhms or if there is a difference between programmed and measured output amplitude of more than 15%. The data also highlight the effect of combining high threshold leads with modern pacemakers with relatively "small" batteries as well as certain problems with telemetered data.
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