Human ovarian carcinomas: correlation of malignancy and survival with the expression of epidermal growth factor receptors (EGF-R) and EGF-like factors (EGF-F)

We have studied the concentration of epidermal growth factor receptors (EGF-R) in 115 different malignant ovarian tumors (101 ovarian carcinomas) and EGF-like factors (EGF-F) in tissue extracts of 63 different ovarian carcinomas and 20 non-malignant tissues. 36% of ovarian carcinomas are EGF-R positive. The calculated mean EGF-F level of 4.2 ± 1.5 ng mg⁻¹ (range: 0–15 ne mg⁻¹) in ovarian carcinomas is significantly enhanced compared to 1.5 ± 0.7 ng mg⁻¹ (range: 0–4 ng mg⁻¹) of non-malignant tissue extracts. The correlation between EGF-R positive as well as negative ovarian carcinomas and the results of a primary chemotherapy of advanced ovarian carcinomas (n = 92) revealed a significantly higher remission rate of EGF-R positive tumors (66%) compared to EGF-R negative cases (23%). 84% of tumors with progressive disease were EGF-R negative. The mean EGF-F levels were calculated for prognostic subgroups of ovarian carcinomas. Increased EGF-F levels are significantly associated with progressive disease compared to all patients or the remission group. 15/16 cases with EGF-F levels > 5 ng mg⁻¹ showed progressive disease. The overall survival time of patients with tumor tissue EGF-F levels > 3.5 ng mg⁻¹ was worse than that of patients with low EGF-F levels. Multivariate analysis showed that the EGF-F level was, after gracling, the second most important factor for predicting overall survival. Supported by Deutsche Forschungsgemeinschaf (DFG), SFB 31.     

155. Zur Problematik des Hypersplenismus bei gutartigen Erkrankungen

Zusammenfassung Die Auswertung von 98 Splenektomien wegen M. Werlhof und die klinische Nachuntersuchung von 51 Patienten ergab, daß sich der Remissionserfolg anhand folgender Parameter abschätzen läßt: Liegen die Thrombocyten bei Diagnosestellung > 10,000/mm³ oder steigen unter Corticoidtherapie auf > 10,000/mm³ besser > 50,000/mm³ an, sind vor allem bei Milzvergrößerung die Erfolgsaussichten der Splenektomie sehr gut. Steigen die Thrombocyten 2 Wochen postoperativ > 100,000/mm³, entwickeln 94,1% der Patienten eine dauerhafte Vollremission. Die Frühergebnisse 2 Wochen postoperativ und die Nachuntersuchung 3 Monate bis 6 Jahre nach Splenektomie ergab eine fast identische Quote von über 80% dauerhaften Vollremissionen und über 12% Teilremission.     

Efficacy of fleroxacin in experimental methicillin-resistant Staphylococcus aureus endocarditis.

The efficacy of fleroxacin versus that of vancomycin was assessed by using the rabbit model of methicillin-resistant Staphylococcus aureus endocarditis. Animals were treated with fleroxacin (30 mg/kg of body weight every 8 h) or vancomycin (17.5 mg/kg every 6 h) for 4 days. These antimicrobial agents were equally effective in clearing bacteremia, reducing bacterial counts in vegetations and tissues, and curing endocarditis. However, resistance to fleroxacin at fivefold the MIC arose in the test strain of S. aureus in 8% of animals that received the drug. We conclude that fleroxacin is as efficacious as vancomycin in this model of a serious systemic S. aureus infection, but modest resistance to fleroxacin may develop during therapy.     

Hermann Graf Vitzthum von Eckstaedt

Ohne Zusammenfassung     

The use of OKT3 in steroid-resistant rejections following cadaveric kidney transplantation

OKT3 has been proved to be effective in the treatment of steroid-resistant rejection after renal allograft transplantation [1]. We investigated the clinical course of OKT3 recipients to find out in which cases of steroid resistance OKT3 therapy might be ineffective.     

The urokinase receptor (CD87) facilitates CD11b/CD18-mediated adhesion of human monocytes.

Urokinase receptors (uPAR; CD87) from complexes with complement receptor 3 (CR3) (CD11b/CD18), a beta2 integrin. In this study, we sought to determine if this association modulates the adhesive function of CR3. Both CR3 and uPAR concentrate at the ventral surface of fibrinogen-adherent human monocytes, and CR3-uPAR coupling increases substantially upon adhesion to fibrinogen. Pretreatment with anti-uPAR monoclonal antibody reduced adhesion to CR3 counterligands (fibrinogen and keyhole limpet hemocyanin) by 50%, but did not affect adhesion to fibronectin, a beta1 integrin counterligand. Antisense (AS) oligonucleotides were used to determine if selectively suppressing uPAR expression also modulates CR3 adhesive function. AS-uPAR oligo reduced CR3-dependent adhesion by 43+/-9% (P<0.01), but did not affect CR3-independent adhesion. To determine if the effects of uPAR are mediated through its ligand, monocytes were pre-treated with AS oligo to block uPA expression. Unlike the effects of blocking uPAR expression, AS-uPA oligo increased adhesion by 46% (P<0.005), and exogenous intact uPA, but not uPA fragments, reversed this effect. We conclude that complex formation with uPAR facilitates the adhesive functions of CR3. This function of uPAR is not dependent upon its occupancy with uPA, which negatively influences adhesion.     

Influence of Supersaturation on the Pharmacodynamic Effect of Bupranolol After Dermal Administration Using Microemulsions as Vehicle

Transdermal absorption of drugs is limited by the stratum corneum, which serves as a diffusion barrier. This barrier might be overcome by enhancing the thermodynamic activity of the drug vehicle. Ther-modynamic activity is particularly high in supersaturated systems because it is directly correlated with the degree of saturation. Since supersaturated systems are not stable, they were formed in situ by application of water-free microemulsion bases. These water-free mi-croemulsion bases saturated with the drug were applied to New Zealand albino rabbits with an occlusive patch. Occlusion leads to water uptake from the skin due to hydratation and changes the microemulsion base into a microemulsion. The microemulsion will become supersaturated as a result of decreasing solubility of the drug with increasing water content. The pharmacodynamic effect of the model drug bupranolol in vivo was investigated over a 10-hr time period. The in vitro solubility of bupranolol was examined with respect to the water content. The solubility vs water content curves were compared to the effect vs time curves. The microemulsions and their individual components were studied, and the effect vs time curves were inversely correlated with the solubility vs water content curves.     

On spinal osteochondromas.

Osteochondromas (or osteocartilaginous exostoses) make up about 30% to 40% of benign bone tumors. Most are solitary lesions but some are multiple, usually with autosomal dominant inheritance. From 1% to 4% of osteochondromas occur in the spine, where they can cause a variety of signs and symptoms, including those of spinal cord or spinal root compression. The authors present five patients with osteochondromas of the spine and review the findings together with those of over 130 cases reported since 1907. The cases were divided into: 1) spinal osteochondromas in patients with multiple osteochondromas, and 2) solitary osteochondromas occurring in the spine. The age (mean +/- standard error of the mean) of patients in the first group was 21.6 +/- 1.8 years compared to 30.0 +/- 2.1 years for those in the second group (p less than 0.02). There was a significant male predominance overall (M:F = 2.5:1; p less than 0.0005). In both groups, one-half of the lesions involved the cervical spine. Symptoms are caused by pressure on adjacent structures. Spinal cord compression was reported more than twice as frequently in the multiple osteochondroma group as in the single osteochondroma group (77% vs 33%; p less than 0.0005). Computerized tomography (CT) is the imaging procedure of choice. In both groups, the majority of surgically treated patients (90% and 88%, respectively) improve, with about three-quarters of the improved patients having no residual disease or only minor deficits.     

Cortical neurons: isolation of contrast gain control.

The selectivity of cortical neurons remains invariant with contrast, even though the contrast-response function saturates. Both the invariance and the saturation might be due to a contrast-gain control mechanism. To test this hypothesis, a drifting grafting was used to measure the contrast-response function, while a counterphase grating was simultaneously presented at the null position of the receptive field (where it evokes no response at any contrast). When the contrast of the counterphase grating increased, the contrast-response function shifted primarily to the right. This result is consistent with the hypothesis that there is a fast-acting gain-control mechanism which effectively scales the input contrast by the average local contrast.