Diagnostic problems in local recurrence after breast saving treatment]

353 patients with stages pTis, pT1-2, pN0-1, cM0 breast cancer have been treated consecutively by breast conserving therapy in a prospective, nonrandomized study at the University Hospital Basel and the Women's Clinic Rheinfelden/Baden/Germany. The median age was 47 years, the median follow-up time 67 months, and 4% only of this collective were lost to follow-up after a median time of 42 months. In 79% of the cases the tumor was excised totally, while in 19% the resection margins were positive and in 2% only the margins were not available for histological judgement. The rate of local failure reached 8% with a median time interval of 53 months. 116 patients showed postactinic induration in the primary tumor region. 73 of these were given additional diagnostic examination: The postactinic induration was judget clinically suspicious in 51 cases and clinically nonsuspicious of local failure in 22 cases. All 73 patients received additional examination by mammography and biopsy. By comparison with the histological results the clinical results were correct in 59% and false in 41%, while the mammographic results were correct in 82% and false in 18% of the cases.     

Enhanced endothelialization of expanded polytetrafluoroethylene grafts by fibroblast growth factor type 1 pretreatment.

BACKGROUND. Biomaterial pretreatment with endothelial cell mitogens may enhance endothelialization. METHODS. Modified fibrin glue (FG) containing 1 ng/cm2 recombinant 125I-labeled fibroblast growth factor type 1 (125I-FGF-1), 20 micrograms/cm2 heparin, 2.86 mg/cm2 fibrinogen, and 2.86 x 10(-2) units/cm2 thrombin was pressure perfused into expanded polytetrafluoroethylene (ePTFE) grafts. Grafts were interposed into infrarenal aortas of 24 New Zealand white rabbits and explanted after 0, 5, 30, and 60 minutes and 1, 7, 14, and 30 days. Residual radioactivity was determined by gamma-counting. Remaining 125I-FGF-1 is expressed as percent of value at time 0. To determine the effect of the FG/FGF-1 on graft healing, three groups of 50 x 4 mm 60 microns internodal-distance nonreinforced ePTFE grafts were implanted in the aortoiliac position of 12 dogs. Group I (n = 12) contained the complete modified FG, group II (n = 6) contained FG with heparin but no FGF-1, and group III (n = 6) contained untreated identical ePTFE. Tritiated thymidine (0.5 microCi/kg) was injected intramuscularly 10 hours before explantation after 7 and 28 days for light and electron microscopy and en face autoradiography. RESULTS. Retention of 125I-FGF-1 showed rapid initial loss (delta %/delta min = -24.1) followed by slow loss after 1 hour (delta %/delta min = -0.03), with 13.4% +/- 6.9% remaining at 1 week and 3.8% +/- 1.1% at 30 days. Every FG/FGF-1 graft at 28 days showed extensive capillary ingrowth and confluent endothelialized luminal surfaces, not seen in any specimen of the other two groups. Autoradiography revealed a significant increase (p less than 0.05) in 3H-thymidine incorporation in the FG/FGF-1 grafts at 28 days versus all groups as a function of time and graft treatment. CONCLUSIONS. Pressure perfusion of an FGF-1/FG suspension into 60 microns internodal-distance ePTFE grafts promotes endothelialization through capillary ingrowth and increased endothelial cell proliferation.     

Urethral stricture after TURP and transvesical prostatectomy]

In an attempt to elucidate factors predisposing to the occurrence of urethral stricture after transurethral resection of the prostate, we performed a prospective follow-up of 178 patients over 12-20 months. We took account of 11 factors that we considered important. Urethral strictures developed in 14.04% of the patients. The resection operations were carried out by five different surgeons, who had different rates of stricture. The only one of the 11 factors studied that was found to involve a statistically significant risk was the presence of an indwelling catheter for more than 3 days. No other factor influenced the result. This patient group was compared with a group of 73 patients followed up for 12-60 months following transvesical prostatectomy. In this group only one stricture (1.36% incidence rate) was observed retrospectively. It seems that urethral ischaemia might increase the risk of urethral stricture. Urethral injuries are considerably less frequent with open prostatectomy. Therefore, we recommend transvesical prostatectomy for pronounced prostatic hyperplasias.     

Extracellular matrix formation by osteoblasts from patients with osteogenesis imperfecta.

Extracellular matrix proteins synthesized by bone cells isolated from 16 patients with different forms of osteogenesis imperfecta (OI) were analyzed in vitro. Specific components of the extracellular matrix by OI and age-matched cultures were investigated by steady-state radiolabeling followed by quantitation of label into specific proteins and comparison of OI cultures to those of age-matched controls. The in vitro proliferation of OI bone cells was found to be lower than that of control cells. In seven patients, abnormalities of the alpha 1(I) and/or alpha 2(I) chains of type I collagen were detected by gel electrophoresis. In two of these patients, the mutations in the COLIA1 and COLIA2 genes have been previously identified. Although the amount of total protein synthesized by the cells in culture was the same for OI bone cells and age-matched control cells, OI bone cells showed a significantly reduced synthesis of not only collagen but also other bone matrix glycoproteins. The synthesis of osteonectin (SPARC/BM40) and three proteoglycans [a large chondroitin sulfate proteoglycan, biglycan (PGI), and decorin (PGII)] was found to be decreased in OI cells. The reduction was most pronounced at the developmental age at which these macromolecules reach maximal levels during normal development.     

Pollen extracts reduce the hepatotoxicity of paracetamol in mice

Cernitins are preparations obtained from plant pollen which contain numerous compounds of potential biological significance. This work deals with the influence of cernitins upon acute paracetamol toxicity in mice. The survival rate and indices of hepatic injury: aminotransferase and alkaline phosphatase activities, bilirubin level in serum, glutathione and cytochrome P-450 content in liver, liver weight, histopathologic picture of the liver and presence of glycogen and lipids in stained liver sections, under different experimental protocols, were determined. It was found that cernitins are able to increase the survival rate of mice and reduce liver injury in acute paracetamol poisoning. Cernitins are more effective when administered after, rather than before, a dose of paracetamol. The possible mechanism through which cernitins may act is discussed.     

Hereditary deficiency of antithrombin III, protein C and protein S: prevalence in patients with a history of venous thrombosis and criteria for rational patient screening.

Data in the literature on the prevalence of hereditary deficiency of the natural coagulation inhibitors are conflicting. We conducted a prospective study on 680 consecutive patients with a history of venous thrombosis to determine the prevalence of hereditary deficiency of antithrombin III (AT III), protein C(PC) and protein S(PS) and to establish selection criteria for rational patient screening. The mean age of the patients at investigation was 44.3 +/- 15.4 years, while that at the first thrombotic event was 38.5 +/- 14.8 years. The total prevalence of inhibitor deficiency states was 48/680 (7.1%). 19/680 patients (2.8%) had AT III-deficiency, 17 (2.5%) PC-deficiency, nine (1.3%) PS-deficiency and three (0.4%) a combined deficiency. In 37/48 deficient patients family studies were performed and the hereditary nature was established in 19 cases (2.8% of total patient population, six with AT III-deficiency, eight with PC-deficiency, four with PS-deficiency and one with a combined deficiency). Family studies in these 19 patients revealed 46 additional individual patients with a hereditary deficiency state. A positive family history was found in 15/19 (79%) with a proven hereditary deficiency state, in 153/619 (25%) of non-deficient patients and in 11/29 (38%) of deficient patients without established hereditary nature. The mean age at the first thrombotic event was significantly lower in patients with a hereditary deficiency state (26.8 years) compared with the other two groups (39.0 and 39.7 years, respectively). In all patients with a hereditary deficiency the first thrombotic event occurred before the age of 45 years.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of aspirin and indomethacin on epidermal growth factor secretion in duodenal tissue fragments cultivated in vitro.

The aim of the present study was to determine the effect of aspirin and indomethacin on epidermal growth factor (EGF) secretion in duodenal tissue fragments cultivated in vitro. The fragments were obtained from healthy subjects by gastroscopy, cultured in McCoy's medium and gassed with 95% O2 and 5% CO2 at 37 degrees C. After an incubation of 30 min, the culture medium was decanted, and the quantity of hormone determined by radioimmunoassay. The mean EGF level detected in the medium was 10.94 ng/mg protein tissue. The addition of aspirin (final concentration 10(-7) M) to the medium reduced mean EGF levels to 7.5 ng/mg (p less than 0.05), whereas aspirin 10(-8) M did not produce such a modification. The addition of indomethacin (final concentration 10(-8) M) decreased mean EGF levels to 5.37 ng/mg (p less than 0.001). In all experimental conditions, the addition of anti-somatostatin (SRIF) antibodies determined a remarkable increase in EGF (p less than 0.01). The results of this study show aspirin and indomethacin to be direct, not SRIF-mediated inhibitors of EGF release.     

Different accessory function for TH1 cells of bone marrow derived macrophages cultured in granulocyte macrophage colony stimulating factor or macrophage colony stimulating factor.

The ability of macrophages to stimulate immune responses is heterogeneous and may have influence on the type of the developing immune response. Therefore, in an attempt to define different functional states of mouse macrophages, we made use of the two macrophage growth factors: macrophage colony stimulating factor (M-CSF) and granulocyte macrophage colony stimulating factor (GM-CSF). Generation of macrophages from freshly isolated bone marrow cells in the presence of GM-CSF results in a population expressing profound antigen presenting function for mouse TH1 cells, resulting in strong lymphokine production and proliferation of the T cells. Furthermore, high amounts of a novel soluble cytokine active on mouse TH1 cells are generated during the interaction of TH1 cells with macrophages elicited with GM-CSF. In contrast, macrophages grown from bone marrow cells for at least 14 days in the presence of M-CSF express only minimal antigen-presenting function for TH1 cells. Treatment of such macrophages for 24 h with either IFN-gamma or GM-CSF allows the distinction between two further functional states. Those treated with IFN-gamma efficiently presented antigen towards TH1 cells. The T cells produced large amounts of lymphokines and proliferate well. However, synthesis of the novel soluble cytokine (active on TH1 cells) was not detectable. The generation of this mediator requires a short-term treatment with GM-CSF of macrophages developed in the presence of M-CSF prior to their interaction with TH1 cells.