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H Graeff

Publications and source records attributed to H Graeff.

At least 73 records · Page 4Linked to original sources
PubMed1994

[Changes in fibrinolysis-associated parameters in HELLP syndrome].

Various parameters associated with fibrinolysis were examined in plasma and placenta tissue extract in 18 patients with HELLP syndrome (haemolysis, elevated liver enzymes, and low platelet count). A significant increase in plasma concentrations of tPA and PAl-1 was observed in the HELLP patients in comparison to 18 pregnant women of the control group (equal duration of pregnancy). In contrast, there was no difference in plasma concentrations of uPA, uPA-receptor and D-dimer. In placenta tissue extract, significant differences were found just as rarely for uPA, uPA-receptor and PAl-1 as for tPA and D-dimer. Our findings indicate, that endothelial damage with release of tPA may be involved in the pathophysiological pathway of HELLP syndrome. Increased plasma levels of PAl-1 may reflect deficient fibrinolysis resulting in impairment in microcirculation. Clinical relevance of tPA and PAl-1 plasma concentration as possible predictor of hypertensive pregnancy complications will have to be studied further.

Adult↗
PubMed1994

[Hydronephrosis as the first manifestation of primary metastatic breast cancer].

Hydronephrosis as the first symptom of primary metastasised breast cancer is described in two case reports. The literature regarding this topic is also discussed. Although retroperitoneal metastases are rarely found, patients with breast cancer should undergo a regular sonographic control of the kidneys, simultaneously with the routine ultrasound of the upper abdomen.

Adult↗
PubMed1994

[Ciprofloxacin/metronidazole vs. cefoxitin/doxycycline: comparison of two therapy schedules for treatment of acute pelvic infection].

The efficacy and safety of two antibiotic regimens for the treatment of acute pelvic inflammatory disease (PID) was compared in a prospective and randomised study. 57 patients received either 0.2 gms ciprofloxacin intravenously b.i.d. in combination with 0.5 g metronidazole intravenously t.i.d. (n = 26), or alternatively 2 g cefoxitin intravenously t.i.d. in combination with doxycycline 0.1 g b.i.d. (n = 31). After commencing therapy intravenously, medication with ciprofloxacin, metronidazole and doxycycline was continued orally after two or three days. In the ciprofloxacin/metronidazole group, PID was found to be severe in 7, moderate in 12 and mild in 7 patients. The numbers in the cefoxitin/doxycycline group were 8, 20 and 3 respectively. The clinical result after treatment with ciprofloxacin/metronidazole was resolution of all symptoms in 24 patients and improvement in 2 others. In the cefoxitin/doxycycline treated group, resolution was found in 27 patients, improvement in 2 others. Failure occurred in 2 patients. 53 different microorganisms as the suspected cause of PID were isolated in the ciprofloxacin/metronidazole group and 56 in the cefoxitin/doxycycline group. According to our clinical and bacteriological criteria, treatment for PID was successful in 97% of the ciprofloxacin/metronidazole group and in 87% of the cefoxitin/doxycycline group. Adverse reactions were found in 4 patients in the ciprofloxacin/metronidazole treated group. Therapy had to be terminated in 3 of these patients. In the cefoxitin/doxycycline group 2 patients had adverse reactions, and therapy had to be terminated in one of these patients. According to our results, both antibiotic regimens can be recommended for the treatment of PID.

Adult↗
PubMed1994

Inactivation of receptor-bound pro-urokinase-type plasminogen activator (pro-uPA) by thrombin and thrombin/thrombomodulin complex.

Urokinase-type plasminogen activator (uPA) binds with high affinity to a specific cell surface glycosyl phosphatidyl-inositol (GPI)-anchored receptor, the urokinase receptor (uPAR). Pro-uPA, the enzymatically inactive single-chain form of uPA after having been activated by certain proteases, converts plasminogen into plasmin. This activation of pro-uPA to enzymatically active uPA can be prevented by the action of thrombin on pro-uPA. This inactivation process is accelerated in the presence of thrombomodulin (TM). The present study investigated whether pro-uPA bound to uPAR is still susceptible to inactivation by thrombin in the presence or absence of TM. A truncated soluble form of the uPAR lacking the GPI-anchor was cloned and expressed in CHO-cells (rec-uPAR277). Rec-uPAR277 efficiently inhibited the thrombin-mediated inactivation of pro-uPA up to 90% in a concentration dependent manner. The protective effect of rec-uPAR277 was far less pronounced when thrombin was complexed with TM. Enzyme kinetic experiments with varying concentrations of pro-uPA showed that in the presence of TM the catalytic efficiency (kcat/Km) of thrombin-mediated inactivation raised from 0.010 microM-1 s-1 to 0.50 microM-1 s-1 corresponding to a fifty-fold increase. In the presence of rec-uPAR277, however, the catalytic efficiency dropped by 4.1-fold (0.5 microM-1 s-1 to 0.122 microM-1 s-1). The inactivation kinetics of pro-uPA by thrombin (no TM added) in the presence of an excess of rec-uPAR277 could not be determined since virtually no inactivation occurred. Our data suggest that pro-uPA once bound to uPAR, is significantly protected from inactivation by thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Urokinase (uPA) and its inhibitor PAI-1 are strong and independent prognostic factors in node-negative breast cancer.

Evidence has accumulated that invasion and metastasis in solid tumors require the action of tumor-associated proteases, which promote the dissolution of the surrounding tumor matrix and the basement membranes. The serine protease urokinase-type plasminogen activator (uPA), which is elevated in solid tumors, appears to play a key role in these processes. We used enzyme-linked immunoassays (ELISA) to test for uPA antigen and its inhibitor PAI-1 in tumor tissue extracts of 247 breast cancer patients who were enrolled in a prospective study. The relation of these data to known prognostic factors and to other variables such as DNA analysis and cathepsin D was studied. Disease-free and overall survival were analyzed according to Cox's proportional hazard model. The major new finding is that breast cancer patients with either high uPA (> 2.97 ng/mg protein) or high content of the uPA inhibitor PAI-1 (> 2.18 ng/mg protein) in their primary tumors have an increased risk of relapse and death. Multivariate analyses revealed uPA to be an independent and strong prognostic factor. The impact of uPA is as high as that of the lymph node status. In node-negative patients the impact of uPA is closely followed by that of PAI-1. Since uPA and PAI-1 are independent prognostic factors, the node-negative patients could be subdivided further by combining these two variables. In this refined analysis, patients whose primary tumors have lower levels of both antigens evidently have a very low risk of relapse (93% disease-free survival at three years) in contrast to patients with high uPA and high PAI-1 (55% disease-free survival at three years). The combination of uPA and PAI-1 in our group of patients with axillary node-negative breast cancer allows us to identify the 45 percent of patients having an increased risk of relapse. Consequently, more than half of the patients had less than a 10% probability of relapse and thus would possibly be candidates for being spared the necessity of adjuvant therapy.

Antigens, Neoplasm↗
PubMed1993

[Importance of plasma PMN granulocyte elastase concentration determination in pregnant patients with premature rupture of fetal membranes].

The aetiology of preterm rupture of membranes is not yet completely understood. Local infections of the vagina and cervix have attracted special attention during the last years. Ascending infection with subsequent chorioamnionitis is a common complication of preterm rupture of membranes. Recognition of the beginning of a chorioamnionitis is usually based on clinical symptoms and laboratory findings like white blood cell count and C-reactive protein. The purpose of this study was to find out the diagnostic value of elastase, a protease of polymorphonuclear granulocytes, which is known to be involved in inflammatory processes. Fifteen out of thirty-three patients with preterm rupture of membranes developed a chorioamnionitis. Elastase plasma concentration levels > or = 32 ng/ml one day before delivery showed a significant correlation (p = 0.02) to the development of a chorioamnionitis. At this time neither white blood cell count, nor rectal body temperature showed significant correlations. Low elastase levels do not exclude an infection, whereas high levels indicate an infectious process. We conclude that elastase is a relevant marker of chorioamnionitis.

Adult↗
PubMed1993

Accumulation of p53 protein as an indicator for p53 gene mutation in breast cancer. Occurrence of false-positives and false-negatives.

Accumulation of p53 protein resulting in levels detectable by immunohistochemistry (IHC) has been proposed as an indicator of mutation of the p53 gene. We have investigated a panel of 23 fresh-frozen breast cancers by IHC (PAb 1801), Southern and Northern blot analysis, and direct sequencing of the mutation hot spot regions (exons 5-8) of the p53 gene. Three tumors (13%) showed an intense nuclear staining in the majority of malignant cells, but only one of these showed a mutation of the p53 gene (codon 237, Arg to His). Furthermore, a mutation (5-bp deletion) was identified in a tumor that showed no p53 immunoreactivity. Our results indicate that accumulation of p53 protein, as detectable by IHC, is not a reliable indicator for p53 gene mutation in human breast cancer.

Base Sequence↗