Biomedical subjects
Publications and source records attributed to S Schmidt.
From August 1989 to April 1990, 511 patients donated preoperative blood for elective cardiothoracic, orthopedic or orthodontic operations. No side effects related to donations showed 64% of the patients, anemia 22%, vaso-vagal reactions 11%. From the autologous units 39% were transfused to the cardiothoracic, 63% to the orthopedic and 68% to the orthodontic patients.
Fetal malformations are detected early in pregnancy by means of ultrasound challenging fetal therapy. While open fetal surgery has been preformed during preliminary clinical trials we evaluated fetoscopic therapy avoiding laparotomy and uterotomy. We used a laser fibre (900 mu) which was introduced into the uterus by an endoscope. During animal experiments in five fetal lambs with a gestational age of 120-122 days we used an excimer laser (Technolas, x) with a wave-length of 308 nm. Laser incisions were compared with the conventional cutting technique using a scapel. During histological evaluation the tissue effect was morphometricly analysed. The zone of devitalisation was characterized by pycnosis of the nuclei and in a change of cytoplasma volume. The excimer laser incisions using a frequency of 40 HZ had a mean zone of devitalisation of 50.3 +/- 4.5 mu. Using the excimer laser with a frequency of 10 HZ we found a tissue alteration of only 11.2 +/- 3.4 mu. The incisions by scapel showed a extended traumatisation with a mean tissue effect of 153.2 +/- 16.3 mu. From these results we conclude, that endoscopic surgery may be come a usefull additional tool for fetal therapy.
Recent progress in the area of prenatal diagnosis by means of ultrasound forces the improvement of surgical techniques for intra-uterine fetal therapy. By the use of short, intense pulses of ultraviolet laser light (20-200 ns long) a photoablation of defined samples of biological tissue is performed with no substantial thermal side effects. The experimental set-up applied in this study included endoscopic operation on five fetal lambs. Macroscopically, a sharp edge in the incision area was observed at both prechosen laser frequencies of 10 and 40 Hz. The clinical application of pulsed ultraviolet laser systems with the characteristics of guided photoablation and atraumatic incisions avoiding thermal side-effects opens new perspectives for fetal surgery.
Sera from diabetes-prone BB/OK rats were tested for humoral-mediated cytotoxicity to rat pancreatic islet cells, spleen lymphocytes and exocrine pancreatic cells using 51Cr-release assay systems. At the age of 20, 30 and 40 days all cross-sectionally studied BB/OK rats showed cytotoxicity to islet cells but only 37.5%, 25.0% and 63.3% of them exhibited anti-lymphocyte cytotoxicity, respectively. Neither the time course of cytotoxicity to islet cells nor to lymphocytes differed in BB/OK rats developing diabetes compared to animals maintaining normoglycaemia as evidenced in a follow-up study. The decrease of cytotoxicity to islet cells in vitro as observed in the time course study seems to be due to the appearance of an inhibitor of anti-islet cell cytotoxicity in serum from BB/OK rats older than 70 days. However, under conditions avoiding the influence of inhibitory components the observed time course of anti-islet cell cytotoxicity also did not permit to distinguish potential diabetic BB/OK rats from animals maintaining normoglycaemia. In contrast, long-term normoglycaemic BB/OK rats showed a peak value of cytotoxicity to rat exocrine pancreatic cells between 40 and 50 days of age only whereas animals developing diabetes more frequently displayed cytotoxicity in the prediabetic phase. Inhibitory activity against cytotoxicity to exocrine cells was not likewise detectable in BB/OK rat serum. In conclusion, except of more frequently appearing cytotoxicity to rat exocrine pancreatic cells among the investigated BB/OK rats becoming diabetic the cytotoxicity patterns to islet cells and spleen lymphocytes were not predictive for diabetes onset. Thus, humoral-mediated cytotoxicity seems to appear in BB/OK rats as a sign of immune dysregulation characteristic for this animal model at high risk for diabetes rather than in a manner related to disease manifestation.
Lipase from porcine pancreas was immobilized on cellulose beads having various degrees of hydrophobicity, by covalent linking and by hydrophobic adsorption. Lipolytic activity was measured in heterogeneous organic-aqueous systems of various hydrophobicities using olive oil as a substrate. The main factors influencing lipase activity were hydrophobicity of the reaction mixture and of the carrier. Carriers with increased hydrophobicity enhanced lipase activity more than less hydrophobic ones. Lipase immobilized covalently on cellulose beads was less active than that adsorbed onto tritylcellulose but was considerably more thermostable.
A nosocomial outbreak of rotavirus gastroenteritis involving 52 newborns occurred between June and September 1988 at the University Children's Hospital of Freiburg, Federal Republic of Germany. Stools from 27 representative patients were examined for rotavirus serotypes, using a monoclonal antibody-based enzyme-linked immunosorbent assay. The electropherotype was also examined by polyacrylamide gel electrophoresis of genomic RNA. As many as 18 patients were found to be infected by serotype 4, subtype 4B strain, and in all of them the same electropherotype was detected. Although rotavirus from the remaining nine patients could not be typed, the electropherotype in four was identical to that of the serotype 4, subtype 4B strain. Thus, most of the patients in the outbreak were infected by the same rotavirus strain. Retrospective epidemiological studies showed that the 4B strain began to circulate at the hospital in January 1988, whereas only rotavirus serotypes 1, 3, and 4A were detected in 1985-1987. The primary case of the outbreak was presumably a newborn with acute gastroenteritis, admitted to the hospital from a small maternity unit in the same urban area. During the outbreak, 12 of 44 healthy newborns in the nurseries of the Children's Hospital and other maternity hospitals were found to be asymptomatic rotavirus carriers, and in three of the newborns the same 4B strain was detected. This is the first reported outbreak caused by a serotype 4, subtype 4B strain.
In a study of 118 psychiatric patients two questionnaires of similar content that are supposed to predict compliance with pharmacotherapy in psychiatry were examined, "COSS" and "KK-Skala". These questionnaires assess the patient's attitudes towards his illness, pharmacotherapy, and the physician. Patient compliance was judged by the treating physicians. The results of discriminant analyses indicated that about two thirds of the patients were correctly classified into "compliant" and "moderately or not compliant" (as judged by the physicians) by means of COSS and KK-Skala, respectively. It is a matter for further research whether these results reflect in fact moderate associations between patient attitudes and compliant behavior or are due to limitations of the questionnaires and of the study design.
We report the results of a phase I study of intravenously administered cisplatin, 5-fluorouracil and high-dose folinic acid. This trial was designed to exploit potential biochemical interactions between these three agents. The maximum tolerated doses were cisplatin, 75 mg/m2, day 1; 5-fluorouracil, 375 mg/m2, days 1-5 and leucovorin 500 mg/m2, days 1-5. The dose-limiting toxic effect of this regimen was myelosuppression. Mild non-hematologic toxic effects were also observed and included nausea, vomiting, stomatitis, and diarrhea. Phase II trial of this regimen are underway, however randomized studies will eventually be necessary to establish whether cisplatin contributes clinically significant activity to this regimen.
The present study investigates whether sera from diabetic BB/OK rats impair beta-cell-specific functions of rat pancreatic islets and whether humoral-mediated cytotoxicity in BB rat sera also affects the autologous islets of normoglycaemic serum donors. Exposure of neonatal rat islets of Langerhans for 20 h to sera from diabetic BB rats and rabbit complement resulted in a decrease in insulin content and in insulin release upon glucose stimulation. However, the extent of islet alterations caused by sera from various BB rats was different as revealed by comparison of the ability of beta-cells to restore their functions during a 48 h recovery period. While the effect of some of the sera was completely reversible, in other cases the insulin content and/or the secretory capacity of the islets could not be fully restored indicating partially irreversible islet alterations due to pretreatment with cytotoxic BB rat serum. The potential effect of anti-islet cytotoxicity in BB rat sera against autologous islets of the serum donor indicated by enhanced 51Cr-release in the presence of rabbit complement was proven in 50% (6/12) of the investigated normoglycaemic BB/OK rats. These results suggest that humoral-mediated cytotoxicity may contribute to beta-cell alteration in this model of diabetes.
Obstetrical management in case of foetal third-degree AV block has been to date mainly via primary abdominal section, the indication being partly the foetal condition and partly also unsatisfactory childbirth monitoring. The article describes a childbirth associated with AV block, monitoring being effected by continuous measurement of the transcutaneous partial carbon dioxide pressure (tcpCO2) and via laser spectroscopy. Prenatal diagnostics and indications for vaginal delivery are also described. Updated knowledge on the pathogenesis of foetal AV block is presented.
Monitors for laser spectroscopy are available as an additional tool for foetal surveillance. Using this technique, continuous and non-invasive registration of four biochemical parameters (HbO2, HbR, blood volume and cytochrome aa3) can be performed. The calculation is based on the optical density after irradiation of the biological sample with pulsed laser light in the near-infrared range (755, 805, 845, 904 nm). We evaluated the new technique in a clinical trial of 20 patients. The application of the laser sensor was performed, using a modified amnioscope. During prenatal tracings in cases with suspect CTG patterns, hypoxia was not verified. In cases without late decelerations a decrease of the cytochrome aa3 signal was observed in less than 1%. During intrapartual measurements, near-infrared signals were compared with the result of the PO2 measurement in foetal blood analysis. We found a significant correlation for HbO2 and cytochrome aa3 with a correlation coefficient of r = 0.96 respectively r = 0.94. We conclude, that laser spectroscopy will potentially be of benefit for foetal monitoring as it might provide a basis for differentiation between foetuses at risk and non-hazardous cases.
Syngeneic transplantation of cultured and functionally characterized neonatal islet into the spleen of streptozotocin diabetic Lewis rats resulted in long time survival up to 200 days and in plasma glucose levels lower than 9 mmol/l. The daily plasma glucose profile of transplanted rats had shown significantly above that of non diabetic control rats. 200 days after transplantation morphologically intact, insulin containing beta-cells were demonstrable in the spleen, thus demonstrating the long-term survival of functioning islet cells. Proliferation of beta-cells was shown in the transplanted islets. In addition, beta-cell clusters were found which derived from pancreatic ductules transplanted together with the isolated islets into the spleen. Mitose were visible within ductular epithelial cells. The proliferative response of islets after intrasplenic transplantation is probably the result of a long-term stimulation by slightly enhanced plasma glucose values of the transplanted acceptors compared to control animals.
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Neonatal rat pancreatic islets can be affected in vitro by ADCC mediated by serum and mononuclear cells from diabetic BB/OK rats or complement-dependent antibody-mediated cytotoxicity (C'AMC) of BB rat serum as revealed by enhanced 51Cr-release. Using a syngeneic islet transplantation system in BB/OK rats this study addressed the question whether the destruction of islets of Langerhans in vivo is reflected by the appearance of ADCC or C'AMC in vitro. The frequency of the appearance of enhanced anti-islet ADCC in newly diagnosed diabetic BB/OK rats amounted to 33% whereas ADCC was not detectable in long-term diabetic rats with a diabetes duration in a range between 50 and 90 days. After transplantation of syngeneic islets beneath the kidney capsule of long-term diabetic BB/OK rats held without immunosuppression the destruction of the islet graft and the persistence of hyperglycaemia was accompanied by an increase of anti-islet ADCC in 66.6% of the animals. While only 18.7% of the long-term diabetic BB/OK rats showed C'AMC against islet cells before transplantation this frequency raised after transplantation and 62.8% of the animals exhibited increased C'AMC within a period of 21 days but with a pronounced individual variability of the time-course. Increased anti-islet cytotoxicity (ADCC or C'AMC) parallels newly initiated or reactivated beta-cell destruction after transplantation and thus seems to reflect this process.
The noninvasive determination of biochemical parameters has become an important aspect of intensive care medicine. The newly developed monitors for laser reflectometry provide the possibility of spectroscopic monitoring. The equipment consists of a near-infrared data collection unit and a personal computer. The four laser diodes emit light at wavelengths of 775, 805, 845 and 904 nm. By analyzing the changes in optical density during laser irradiation of biological tissue, information is obtained about the relative changes in the concentration of hemoglobin and the blood volume. In animal experiments with ten fetal lambs we evaluated the reliability of near infrared laser spectroscopy. Fetal hyperoxia was achieved by means of an extracorporeal circuit with interposition of a membrane oxygenator (0.8 m2, Scimed). During the induced hyperoxia the laser spectroscopic tracings showed a rise in the HbO2 signal with a synchronous decrease in the HbR signal. Additionally, the spectroscopic pattern showed a characteristic initial rise in the intracerebral blood volume, which stabilized after 4 minutes. We found a significant correlation between the intermittently measured PO2 values of the arterial blood samples and the laser spectroscopic HbO2 and HbR signals (r = 0.87, and r = -0.82, respectively; p less than 0.001). Furthermore, hyperoxia was indicated by the laser system with a short lag time. We conclude that laser spectroscopy is a reliable method with a high potential for clinical routine use in intensive care, as it provides noninvasive continuous information at comparatively low costs using portable monitors.
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We have previously shown a novel galactose/N-acetylgalactosamine specific lectin activity (Hodgkin's disease (HD) lectin) on the surface of cultured HD cells (lines L428, its variants, and line L540) to mediate lymphocyte adhesion. We here demonstrate that both surface membrane-bound and secreted HD lectin activities participate in the activation of agglutinated lymphocytes. Among known adhesion molecules expressed by the HD cells, only the intercellular adhesion molecule-1 (ICAM-1) contributed to this activation as an alternative PBL binding site. As yet we have not identified the cellular ligand(s) for the HD lectin on the lymphocyte surface. Pretreatment of lymphocytes with mAb to the accessory molecules CD2, CD3, CD4, CD8, CD11b, or CD11c did not interfere with their response to HD cells. mAb to CD11a (LFA-1), the alleged ligand of ICAM-1, inhibited the ICAM-1 but not the HD lectin-mediated lymphocyte stimulation. Although lymphocyte binding could proceed via either pathway, lymphocyte activation always depended upon factors secreted by the HD cells, one of which we identified as a soluble form of the HD lectin based on its shared properties with the membrane-bound form including immunologic cross-recognition and carbohydrate-binding specificity. Although HD cell-conditioned medium alone stimulated lymphocytes, HD cell plasma membranes could compensate for low concentrations of this medium. In addition, resting lymphocytes, normally unresponsive, were triggered into DNA synthesis by growth medium when cocultured with HD cell membranes. The unique functions of the surface-expressed HD lectin and its soluble counterpart as lymphocyte adhesion molecule and mitogen might be physiologically relevant to the severe immunodeficiencies occurring in patients with HD.
By means of protein clearance investigations the differentiation of the damage degree of the kidneys is to be described in a certain extent also with lupus nephritis. The in 1982 stated proteinuria elimination of 0.5 g/24 hour as a criterion for a renal participation could be the cause for the often relatively late stated kidney participation in the LE. The determination of selective and nonselective excreted proteins in connection with the detection of the double strain-DNS antibodies might be more proper to indicate a kidney participation.