Intramedullary pilocytic astrocytomas — a clinical and morphological study after combined surgical and photon or neutron therapy

Ten patients suffering from intramedullary pilocytic astrocytomas (WHO-classification: astrocytoma grade I) were investigated catamnesticly. Combined surgery and radiotherapy was performed. Seven patients received neutron irradiation postoperatively. In four cases the neurological symptoms were improved after follow-up periods ranging from 33 to 89 months. The three other patients died after 6 to 21 months. The autopsy findings of a 14 year old child are presented. Our results are compared with reports in the literature. In addition, long-term problems of the spinal column are discussed. It seems that the combined surgical and neutron therapy improves the prognosis of pencil gliomas.     

Stem cell research and cell transplantation for myocardial regeneration.

Several human organs are not capable of functional regeneration following a tissue defect and react with scar formation. In stem cell transplantation, undifferentiated or partly differentiated precursor cells are applied to defective tissue for therapeutic regeneration. After promising preclinical investigations, the transplantation of autologous stem cells for myocardial infarction treatment is being transferred to clinical use. Mesenchymal stem cells and endothelial precursor cells derived from the bone marrow or circulating blood as well as skeletal myoblasts are employed in clinical trials. Furthermore, indications for cell transplantation and delivery routes vary considerably throughout current investigations. Initial results suggest a potential for restoration of cardiac function in stem cell-treated patients; however, the mechanisms are not fully understood. This overview will focus on objectives, recent achievements, and future perspectives of diverse stem cell transplantation approaches.     

Long-term elevations of dietary sodium produce parallel increases in the renal excretion of urodilatin and sodium

The effects of dietary sodium intake on the renal excretion of urodilatin and of sodium were examined in six healthy male subjects. The 24-day study period was divided into three phases of 8 days each. Subjects Ingested 2.8 mequiv sodium (kg body weight)^–1 day^–1 during the first phase, 5.6 mequiv (kg body weight)^–1 day^–1 during the second phase, and 8.4 mequiv (kg body weight)^–1 day^–1 during the third phase. The excretion of both sodium (P<0.002) and urodilatin (P<0.006) increased in response to the increasing dietary sodium, while urine flow did not change. Urinary urodilatin excretion correlated closely with renal sodium excretion (P<0.001). Serum aldosterone levels (P<0.01) as well as serum renin levels (P<0.05) significantly decreased with increasing sodium intake. Plasma [Arg]vasopressin levels increased significantly (P<0.05). Plasma atrial natriuretic factor and cGMP levels as well as urinary cGMP excretion rates were unaltered by the changes in sodium intake. We conclude from these results that the renal natriuretic peptide, urodilatin, but not the main cardiac member of the natriuretic peptide family may be involved in the regulation of day-to-day sodium balance.     

Quantification and preservation of lectin binding by isolated cardiomyocytes

During preparation of cells for experimentation a considerable amount of bound substance is lost. Our aim was to develop a protocol which retained lectin binding to an extent similar to living cells. This procedure would use fixation procedures suited for fluorescent lectin conjugates and gold-conjugates to be visualized by light- and electron microscopy, respectively. We tested glutaraldehyde and paraformaldehyde in different concentrations before and after lectin binding, different buffers and divalent cations, as additives, to determine the effects on preservation of lectin binding. Lectin binding was visualized and semiquantitatively evaluated by image analysis in the light microscope after silver enhancement of lectin-gold conjugates and by using tetramethyl rhodaminyl isothiocyanate (TRITC)-conjugated lectins. Preservation of lectin binding was best visualized with fluorescent lectin conjugates, whereas during silver enhancement procedures of gold-conjugated lectins, a considerable amount of bound lectins was lost. In general, lectin binding to living cells followed by fixation is superior to fixation before lectin binding. Unfavourable combinations of fixatives and buffers can cause a loss of more than 90% bound lectin. In our experiments with freshly isolated guinea pig cardiomyocytes, lectin binding was best when we used Na-cacodylate buffer with glutaraldehyde fixation (0.1%) after binding of lectins to the living cells.     

Enolase 1 of Candida albicans binds human CD4+ T cells and modulates naïve and memory responses

To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4⁺ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4⁺ T-cell recall responses. Therapeutically, CD4⁺ T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4⁺ T cells with CaEno1 modulated host CD4⁺ T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4⁺ T-cell responses.     

Immediate functional benefits after controlled reperfusion during surgical revascularization for acute coronary occlusion.

This study tests the hypothesis that contractile dysfunction that often develops after acute coronary occlusion despite emergency revascularization can be avoided by careful control of the composition of the initial reperfusate and the conditions of the reperfusion. Between January 1987 and May 1989, 31 consecutive patients with acute coronary occlusion (90% resulting from percutaneous transluminal coronary angioplasty failures) were reperfused during emergency myocardial revascularization according to one of two different protocols. In 23 patients the reperfusate was normal blood given at systemic pressure ("uncontrolled reperfusion"); in eight patients the ischemic segment was reperfused during the first 20 minutes with a regional blood cardioplegic solution (substrate-enriched, hyperosmotic, hypocalcemic, alkalotic, diltiazem-containing) at 37 degrees C at a pressure of 50 mm Hg. Thereafter total bypass was prolonged for an additional 30 minutes before extracorporeal circulation was discontinued ("controlled reperfusion"). Assessment of regional contractility (echocardiography, radionuclide ventriculography), electrocardiographic evidence of myocardial infarction, release of creatine kinase and isoenzyme of creatine kinase, and hospital mortality was performed. Regional contractility was quantified with a scoring system from 0 (normokinesis) to 4 (dyskinesis). Data are expressed as mean +/- standard error of the mean. Both groups were well matched for age, sex, and the distribution of the occluded artery. In the controlled-reperfusion group there was a greater prevalence of previous infarctions (63% versus 43%), additional significant stenosis (1.3 +/- 0.2 versus 0.8 +/- 0.2), and cardiogenic shock (38% versus 17%) compared with the uncontrolled-reperfusion group. Furthermore, the interval between coronary occlusion and reperfusion was significantly longer in the controlled-reperfusion group (4.0 +/- 0.5 versus 2.3 +/- 0.3 hr; p less than 0.05). Regional contractility returned to normal in all patients treated by controlled reperfusion (wall motion score = 0.8 +/- 0.3, normokinesis = 0, slight hypokinesis = 1). In contrast, regional contractility remained severely depressed after uncontrolled reperfusion with normal blood (score 2.5 +/- 0.2; p less than 0.05), with only four of 23 patients with a score less than 2 (2 = severe hypokinesis). Postoperatively enzymes and electrocardiographic changes were similar in both groups. One patient died of mitral insufficiency in the controlled-reperfusion group, despite complete recovery of wall motion in the angioplasty-related artery. Conversely, the four of 23 deaths after uncontrolled reperfusion occurred in patients who sustained infarct in the area of the coronary occlusion (mortality 13% versus 17%). In conclusion, these preliminary clinical results indicate that immediate recovery of segmental contractility can be achieved after acute coronary occlusion if the initial reperfusion is controlled.(ABSTRACT TRUNCATED AT 400 WORDS)     

First experience with gamma probe guided sentinel lymph node surgery in penile cancer

Because of the curative approach, the detection of lymph node metastases in squamous cell carcinoma (SCC) of the penis is of significant clinical relevance. Sentinel lymph node (SLN) identification by means of lymphangiography has been proven to be insufficiently safe. However, the high morbidity of inguinal lymphadenectomy and the considerable individual variability regarding the location of lymph node metastases justify the necessity of a technique that enables the identification of SLNs. Since 1998, SLNs have been intraoperatively identified and selectively dissected, after peritumoral injection of technetium-99m nanocolloid and using lymphoscintigraphy, in three patients (one with malignant melanoma and two with SCC). At least one SLN could be detected in each patient. The maximum surgical time was 30 min. There were no severe complications. Lymph node metastases did not occur in any patient. Upon a mean follow-up of 10 months, all patients are currently free of tumor. Owing to the long-term results of sentinel lymphadenectomy in malignant melanoma of other locations and our preliminary results with respect to penile carcinoma, we consider the current method appropriate as the only primary operation for lymph node staging in early stages and, in combination with modified inguinal lymphadenectomy, in locally advanced stages. Received: 24 November 1999 / Accepted: 21 April 2000