[Impact of DNA image cytometry (ICM) parameter and established prognostic factors on disease free survival (DFS) and overall survival (OS) of node-negative breast cancer (NNBC) patients]. / Bedeutung DNA-Bild-zytometrischer Parameter und etablierter Prognosefaktoren für krankheitsfreies Uberleben (DFS) und Gesamtüberleben (OS) nodal-negativer Mammakarzinompatientinnen.

OBJECTIVE: DNA ICM allows measurement of nuclear DNA content and genotypical grading of malignancy. The aim of this study was to prove the prognostic value of DNA parameter in comparison to established prognostic factors for DFS and OS. PATIENTS AND METHODS: Cytological imprints of 177 unselected primary NNBC patients were subjected to ICM. ICM parameter 2cDI, 5cEE, 9cEE, DNA mean value, proliferation fraction (SG2M) and ploidy were investigated together with established parameter like pT-stages, histology, grading, hormone receptor status and patient age regarding DFS and OS. Univariate and multivariate analysis were performed. RESULTS: Univariate analysis revealed that except ploidy all ICM parameter and pT-stages, histology as well as grading were significant prognostic factors for DFS. However, only 2cDI and pT-stages were proved independent prognostic factors in multivariate analysis. Regarding OS 9cEE, histology and pT-stages were significant factors in univariate analysis. However, only 9cEE and pT-stages were found to be independent prognostic factors in multivariate analysis. CONCLUSIONS: DNA - ICM parameter 2cDI and 9cEE together with pT-stages were proved independent prognostic factors in NNBC patients.

[Comparability of obstetric and perinatal data from England and Germany using standard-primip-groups - maternal and neonatal outcome]. / Vergleichbarkeit geburtshilflicher und perinataler Daten aus England und Deutschland durch Verwendung von Standard-Primip-Gruppen - Befinden von Mutter und Kind.

OBJECTIVE: Aim of the study was to assess whether different birth management of an english and german department can influence the maternal and neonatal outcome. MATERIAL AND METHODS: The database consisted of routinely published data from 1986-95 for two clinical units in Solihull (England) and Ibbenbueren (Germany) comprising 34 820 and 9 053 deliveries respectively. In order to standardise the obstetric risk profiles the heterogeneous primary groups were subdivided into "standard primip groups". A statistical comparison using the "binomial confidence interval method" was carried out. RESULTS: In the standardised comparison induction of labour, duration of labour 1-6 hours, vaginal delivery from cephalic presentation, elective caesarean section, both for cephalic and breech presentation, transfer to the childrens hospital were less frequent in Solihull. On the other hand, Solihull showed more frequent oxytocin administration, fetal blood analysis, epidural anaesthesia, episiotomies, duration of labour > 13 hours, forceps, ventouse and emergency caesarean section deliveries from cephalic presentation, vaginal deliveries or emergency caesarean sections from breech presentation, resuscitation of the newborn using mask and/or drugs, maternal blood loss > 1 000 ml as well as abnormalities of placental separation. Despite the different management of the departments being compared no significant differences in the incidence of perinatal hypoxia as determined by Apgar scores at 5 minutes nor in the fetal mortality rate between the units could be identified. CONCLUSION: Using standardised data the quality of obstetric and perinatal care in England and Germany can be reliably compared. Different birth management does not significantly influence the neonatal outcome.

Mitotic checkpoints: from yeast to cancer.

Separation of chromosomes during mitosis is monitored by a checkpoint that leads to cell-cycle arrest if the chromosomes are not properly attached to the mitotic spindle. Molecular mechanisms controlling this checkpoint have been identified. In addition, loss of this checkpoint has been shown to result in chromosome missegregation in higher eukaryotes and may contribute to the genomic instability observed in human cancers.

[Clinical importance of histology, grading and ploidies in primary breast cancer]. / Zur klinischen Wertigkeit von Histologie, Grading und Ploidie primärer Mammakarzinome.

OBJECTIVE: In order to characterise carcinoma of the breast the determination of ploidy can be used in addition to established prognostic factors such as histology and grading. The aim of the investigation was to establish the association between histology, grading and ploidy and to indicate the prognostic and predictive value of these parameters in relation to disease free survival (DFS) and overall survival (OS). MATERIAL AND METHODS: 125 consecutive cases of primary breast carcinoma occurring between the years 1992-1995 were surveyed. The median follow up time lasted 45 months. Correlation analyses were carried out using the Chi-square test, Kaplan-Meier (univariate) and Cox (multivariate) methods. RESULTS: Histology and grading showed no correlation to ploidy but seems to be of importance for DFS in node-negative breast carcinoma. Ploidy did not influence neither DFS nor OS. Ductal histology appeared to be a useful factor in predicting the response of cases treated with an anti-oestrogen (Tamoxifen) since in this group a higher relapse rate of 25% occurred. CONCLUSIONS: Ploidy appears not to be of clinical importance.

Mad2 transiently associates with an APC/p55Cdc complex during mitosis.

Activation of the mitotic checkpoint pathway in response to mitotic spindle damage in eukaryotic cells delays the exit from mitosis in an attempt to prevent chromosome missegregation. One component of this pathway, hsMad2, has been shown in mammalian cells to physically associate with components of a ubiquitin ligase activity (termed the anaphase promoting complex or APC) when the checkpoint is activated, thereby preventing the degradation of inhibitors of the mitotic exit machinery. In the present report, we demonstrate that the inhibitory association between Mad2 and the APC component Cdc27 also takes place transiently during the early stages of a normal mitosis and is lost before mitotic exit. We also show that Mad2 associates with the APC regulatory protein p55Cdc in mammalian cells as has been reported in yeast. In contrast, however, this complex is present only in nocodazole-arrested or early mitotic cells and is associated with the APC as a Mad2/p55Cdc/Cdc27 ternary complex. Evidence for a Mad2/Cdc27 complex that forms independent of p55Cdc also is presented. These results suggest a model for the regulation of the APC by Mad2 and may explain how the spindle assembly checkpoint apparatus controls the timing of mitosis under normal growth conditions.

Overexpression of the G1-cyclin gene CLN2 represses the mating pathway in Saccharomyces cerevisiae at the level of the MEKK Ste11.

Basal and induced transcription of pheromone-dependent genes is regulated in a cell cycle-dependent way. FUS1, a gene strongly induced after pheromone treatment, shows high mRNA levels in mitosis and early G1 phase of the cell cycle, a decrease in G1 after START and again an increase in S phase. Overexpression of CLN2 was shown to repress the transcript number of pheromone-dependent genes (1). We asked whether the activities of components of the mating pathway fluctuate during the cell cycle. We were also interested in determining at what level Cln2 represses the signal transduction machinery. Here we show that the activity of the mitogen-activated protein kinase Fus3 indeed fluctuates during the cell cycle, reflecting the oscillations of the gene transcripts. CLN2 overexpression represses Fus3 kinase activity, independently of the phosphatase Msg5. Additionally, we show that the activity of the MEK Ste7 also fluctuates during the cell cycle. Increased Cln2 levels repress the ability of hyperactive STE11 alleles to induce the pathway. G protein-independent activation of Ste11 caused by an rga1 pbs2 mutation is resistant to high levels of Cln2 kinase. Therefore our results suggest that Cln2-dependent repression of the mating pathway occurs at the level of Ste11.

Mcm1 is required to coordinate G2-specific transcription in Saccharomyces cerevisiae.

In the budding yeast Saccharomyces cerevisiae, MCM1 encodes an essential DNA-binding protein that regulates transcription of many genes in cooperation with different associated factors. With the help of a conditional expression system, we show that Mcm1 depletion has a distinct effect on cell cycle progression by preventing cells from undergoing mitosis. Genes that normally exhibit a G2-to-M-phase-specific expression pattern, such as CLB1, CLB2, CDC5, SWI5, and ACE2, remain uninduced in the absence of functional Mcm1. In vivo footprinting experiments show that Mcm1, in conjunction with an Mcm1-recruited factor, binds to the promoter regions of SWI5 and CLB2 at sites shown to be involved in cell cycle regulation. However, promoter occupation at these sites is cell cycle independent, and therefore the regulatory system seems to operate on constitutively bound Mcm1 complexes. A gene fusion that provides Mcm1 with a strong transcriptional activation domain causes transcription of SWI5, CLB1, CLB2, and CDC5 at inappropriate times of the cell cycle. Thus, Mcm1 and a cooperating, cell cycle-regulated activation partner are directly involved in the coordinated expression of multiple G2-regulated genes. The arrest phenotype of Mcm1-depleted cells is consistent with low levels of Clb1 and Clb2 kinase. However, constitutive CLB2 expression does not suppress the mitotic defect, and therefore other essential activities required for the G2-to-M transition must also depend on Mcm1 function.

[Fulminating E. coli sepsis in Fournier's gangrene]. / Foudroyante E. Coli-Sepsis bei Fournierscher Gangrän.

Fournier's gangrene is a necrotising soft-tissue infection of the scrotum and perineal region caused by gram-negative and gram-positive Enterobacteriaceae. The disease is characterised by its unique appearance, its speed of onset, and its high mortality. CASE REPORT. A 26-year-old male presented to the emergency room complaining of a painful, tremendously swollen scrotum and penis (Fig. 1) that had developed within the past 24 h. Later, slurred speech, pallor, and hypotension were recognised, leading to the patient's admission to the intensive care unit. Suspecting a severe internal haemorrhage, vigorous volume therapy was started using crystalloids and colloids until blood and fresh frozen plasma were available. One hour later, septic shock was presumed and therapy augmented by IV antibiotics, tracheal intubation, and mechanical ventilation. Despite all efforts, the patients condition deteriorated rapidly and he died a few hours later due to multiple organ failure in septic shock. Postmortem, a perforated external hemorrhoidal node was found to be the primary focus of sepsis. Microbiologic cultures revealed Escherichia coli in blood and tissue samples. DISCUSSION. Fournier's gangrene is a rare disease; nevertheless, its clinical picture has to be recognised immediately in order to provide appropriate treatment in time. It occurs predominantly in males after minor trauma, colorectal or urological disease, and perineal or abdominal surgery. Fournier's gangrene usually begins with itching and pain in the scrotal region followed by swelling and dark-blueish discolouration of the scrotum and penis, occasionally including the lower abdominal wall. Fever and chills are usually present. The illness progresses to severe prostation and septic shock with a mortality of 20%-50%. Tissue cultures mostly reveal E. coli, gram-positive enterococci, Pseudomonas, Proteus, and various anaerobes. The treatment should include immediate radical surgical debridement, i.v. administration of broad-spectrum antibiotics, and cardiopulmonary support. CONCLUSION. The dramatic course of Fournier's gangrene requires early recognition, extensive surgical debridement, as well as intensive care treatment in order to prevent irreversible septic shock.

[Localization and extent of tissue damage caused by extracorporeal lithotripsy (ESWL)]. / Lokalisation und Ausmass einer Gewebeschädigung durch die extrakorporale Lithotrypsie (ESWL).

Extracorporeal shock wave lithotripsy (ESWL) causes proteinuria. In our study we investigated the protein fractions and the electrolyte composition of the urine in patients who had been treated with ESWL. The aim was to obtain information on the degree and the localisation of the glomerular, tubular or vascular destruction caused by ESWL in humans. A total of 34 patients with stones had been treated with ESWL. As parameters we used: urine output, creatinine clearance, total protein, albumin, immunoglobulin G, N-acetyl-beta-D-glucosaminidase (beta-NAG), alpha-1-microglobulin, the fractional excretion of Na+ and apolipoprotein-A-1. After ESWL treatment proteinuria and albuminuria are found. Our parameters show no deterioration of the glomerula or the tubulus. The increase in apolipoprotein-A-1, a postglomerular parameter, however, is interpreted as a manifestation of vascular destruction after ESWL; this is normally temporary, leaving no permanent damage.

[Extracorporeal shockwave lithotripsy with combined ultrasound and roentgenologic calculus localization. Initial clinical experiences with the Lithostar plus]. / Extrakorporale Stosswellenlithotripsie mit kombinierter sonographischer und röntgenologischer Steinortung. Erste klinische Erfahrungen mit dem Lithostar plus.

Since the introduction of extracorporeal shock wave lithotripsy for non-invasive treatment of renal and ureteral stones, lithotripter units have relied on either fluoroscopic or ultrasound stone localization. While ultrasound stone localization reduces X-ray exposure and facilitates treatment of radiolucent renal stones, fluoroscopic stone localization is superior in the detection of ureteral stones. Since April 1989 we have been using the Lithostar plus, a new lithotriptor system, which provides both fluoroscopic and ultrasound stone localization. After treatment of 108 patients, the initial data suggest that this system combines the advantages of both localization principles, while being as efficient as other second-generation lithotriptor units in bringing about the disintegration of renal and ureteral stones.