Treatment with Ca2+ ionophore improves embryo development and outcome in cases with previous developmental problems: a prospective multicenter study.

STUDY QUESTION: Does calcium ionophore treatment (A23187, calcimycin) improve embryo development and outcome in patients with a history of developmental problems/arrest? SUMMARY ANSWER: Application of A23187 leads to increased rates of cleavage to 2-cell stage, blastocyst formation and clinical pregnancy/live birth. WHAT IS KNOWN ALREADY: Studies on lower animals indicate that changes in intracellular free calcium trigger and regulate the events of cell division. In humans, calcium fluctuations were detected with a peak shortly before cell division. Interestingly, these calcium oscillations disappeared in arrested embryos. Mitotic division blocked with a Ca(2+) chelator could be restored by means of ionophores in an animal model. STUDY DESIGN, SIZE, DURATION: This prospective, multicenter (five Austrian centers), uncontrolled intervention study (duration 1 year) includes 57 patients who provided informed consent. PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria were complete embryo developmental arrest in a previous cycle (no transfer), complete developmental delay (no morula/blastocyst on Day 5), or reduced blastocyst formation on Day 5 (≤15%). Severe male factor patients and patients with <30% fertilization rate after ICSI were excluded because these would be routine indications for ionophore usage. The total of the 57 immediately preceding cycles in the same patients constituted the control cycles/control group. In the treatment cycles, all metaphase II-oocytes were exposed to a commercially available ready-to-use ionophore for 15 min immediately after ICSI. After a three-step washing procedure, in vitro culture was performed as in the control cycles, up to blastocyst stage when achievable. MAIN RESULTS AND THE ROLE OF CHANCE: Fertilization rate did not differ (75.4 versus 73.2%); however, further cleavage to 2-cell stage was significantly higher (P < 0.001) in the ionophore group (98.5%) when compared with the control cycles (91.9%). In addition, significantly more (P < 0.05) blastocysts formed on Day 5 in the study compared with the control group (47.6 versus 5.5%, respectively) and this was associated with a significant increase (P < 0.01) in the rates of implantation (44.4 versus 12.5%), clinical pregnancy (45.1 versus 12.8%) and live birth (45.1 versus 12.8%). All babies born at the time of writing (22/28) were healthy. LIMITATIONS, REASONS FOR CAUTION: The frequency of patients showing embryo developmental problems was expected to be low; therefore, a multicenter approach was chosen in order to increase sample size. In one-third of the cycles, the clinician or patient requested a change of stimulation protocol; however, this did not influence the developmental rate of embryos. WIDER IMPLICATIONS OF THE FINDINGS: This is the first evidence that developmental incompetence of embryos is an additional indication for ionophore treatment. The present approach is exclusively for overcoming cleavage arrest. STUDY FUNDING/COMPETING INTERESTS: No funding received. T.E. reports fees from Gynemed, outside the submitted work. All co-authors have no interest to declare.

[Sociodemographic aspects are associated with breast cancer screening behaviour of female patients: results of a cross-sectional survey]. / Soziodemografische Aspekte stehen im Zusammenhang mit dem Brustkrebsscreeningverhalten von Patientinnen: Ergebnisse einer Querschnittsuntersuchung.

In Austria, opportunistic mammography screening for detection of early-stages breast cancer is offered for women older than 40 years. In spite of public discussions on the effectiveness of mammography screening, evidence-based educative information material for female patients available online and in print is lacking. The present study describes the influence of the 3 sociodemographic characteristics migration background, education, and age on the individual's breast cancer screening behaviour as well as on the usage of various information sources on breast cancer for patients. In total, 333 outpatients of the Department of Obstetrics and Gynaecology, General Hospital, Vienna, Austria, participated in a monocentric cross-sectional study. Regarding breast cancer screening, 93.4% (n=282) of the female patients had at least one previous mammogram. Furthermore, 86.3% of the participants regularly consulted their gynaecologist, while women with migration background reported less frequent (p=0.02), and well-educated as well as older patients reported more frequent (p<0.02) gynaecological consultations. Higher-educated women (p=0.04) and participants aged between 50 and 69 years (p<0.05) felt better informed on breast cancer-related topics, whereas a migration background was not associated with the perceived level of information. Medical doctors (67.9%) as well as pertinent folders (33%) were the most relevant information sources on breast cancer. Mass media (22.8%) were also a relevant information source on this issue, whereas the Internet (10.5%) was quite rarely referred to for this purpose. The results of the present study show that female patients perceived the medical doctor as the most important source of medical information on breast cancer. The public health-care system could facilitate positive health communication in the doctors/patient relationship by providing homogenous, quality assured educative information material.

The Herbal Drug Melampyrum pratense L. (Koch): Isolation and Identification of Its Bioactive Compounds Targeting Mediators of Inflammation.

Melampyrum pratense L. (Koch) is used in traditional Austrian medicine for the treatment of different inflammation-related conditions. In this work, we show that the extracts of M. pratense stimulated peroxisome proliferator-activated receptors- (PPARs-) α and - γ that are well recognized for their anti-inflammatory activities. Furthermore, the extract inhibited the activation of the proinflammatory transcription factor NF- κ B and induction of its target genes interleukin-8 (IL-8) and E-selectin in vitro. Bioassay-guided fractionation identified several active flavonoids and iridoids including melampyroside and mussaenoside and the phenolic compound lunularin that were identified in this species for the first time. The flavonoids apigenin and luteolin were distinguished as the main components accountable for the anti-inflammatory properties. Apigenin and luteolin effectively inhibited tumor necrosis factor α (TNF- α )-induced NF- κ B-mediated transactivation of a luciferase reporter gene. Furthermore, the two compounds dose-dependently reduced IL-8 and E-selectin protein expression after stimulation with lipopolysaccharide (LPS) or TNF- α in endothelial cells (ECs). The iridoids melampyroside and mussaenoside prevented the elevation of E-selectin in LPS-stimulated ECs. Lunularin was found to reduce the protein levels of the proinflammatory mediators E-selectin and IL-8 in ECs in response to LPS. These data validate the ethnomedical use of M. pratense for the treatment of inflammatory conditions and point to the constituents accountable for its anti-inflammatory activity.

Mode of delivery is associated with maternal and fetal endocrine stress response.

OBJECTIVE: To determine whether mode of delivery is associated with the endocrine stress response in mother and child. DESIGN: Prospective observational study. SETTING: Tertiary care centre, University hospital. POPULATION: A total of 103 nulliparous women with uncomplicated singleton pregnancies at term undergoing either spontaneous labour for vaginal delivery or delivering by caesarean section without labour. Thirty women delivered vaginally without any pain relief, 21 women delivered vaginally with epidural anaesthesia, 23 women had ventouse extraction and 29 women underwent caesarean section with epidural analgesia. METHODS: After delivery, maternal and umbilical cord blood was collected for determination of different stress-associated hormones. MAIN OUTCOME MEASURES: Concentrations of epinephrine (EP), norepinephrine (NOR), adrenocorticotropic hormone (ACTH), cortisol (CORT), prolactin (PRL), corticotropin-releasing factor and beta-endorphin (BE). RESULTS: Caesarean section was associated with significantly lower maternal concentrations of EP, NOR, ACTH, CORT, PRL and BE and lower newborn levels of EP, NOR and CORT compared with all other modes of delivery. Concentrations of EP, ACTH and BE differed significantly in newborns delivered by normal vaginal delivery, vaginal delivery with epidural anaesthesia and ventouse extraction. CONCLUSIONS: The mode of delivery and analgesia used during birth are associated with maternal and fetal endocrine stress responses.

Early detection of preeclampsia by determination of platelet aggregability.

Preeclampsia is still a leading cause of maternal and fetal morbidity and mortality. There is evidence for the involvement of platelets. Therefore, we investigated the suitability of corrected whole blood impedance aggregometry as an early predictor of preeclampsia in 71 consecutive, high-risk pregnancies. According to the occurrence of preeclampsia, defined postpartum by an independent investigator, and the stage of pregnancy (early and late, cutoff: 25 weeks of gestation), four study groups were defined. Platelet aggregation data were corrected for the influence of hematocrit and platelet count by a special purpose software package. Women developing preeclampsia showed significantly higher platelet aggregation response compared to controls in early and late pregnancy. In early pregnancy, all women developing preeclampsia had aggregation responses to collagen higher than the highest responses among the controls. Hence, this test had a 100% positive predictive value of subsequent preeclampsia. Despite being significantly increased, platelet aggregability was of minor predictive value in late pregnancy. We conclude that preeclampsia is accompanied by exaggerated platelet aggregability, particularly perceptible early in the course of pregnancy. We propose collagen-induced whole blood platelet aggregation with correction for the influence of hematocrit and platelet count for early detection of preeclampsia.

Chronic liver injury alters basal and stimulated nitric oxide production and 3H-thymidine incorporation in cultured sinusoidal endothelial cells from rats.

BACKGROUND/AIM: Under pathological conditions the nitric oxide synthase (NOS)-mediated nitric oxide production of sinusoidal endothelial cells might be altered. Therefore, studies were performed to evaluate the nitrite formation by cultured sinusoidal endothelial cells from rat livers chronically injured by thioacetamide and the effect of endogenously or exogenously generated nitric oxide on their proliferative activity. METHODS: Basal and stimulated nitrite formation, expression of NOS and DNA synthesis were examined in sinusoidal endothelial cells isolated and cultivated from livers with incipient or advanced chemically-induced cirrhosis. RESULTS: Cultured sinusoidal endothelial cells from injured livers exhibited a reduced basal and an increased lipopolysaccharide-stimulated nitrite production when compared with controls. Western blot analysis revealed a markedly reduced protein expression of endothelial NOS (eNOS) and inducible NOS (iNOS) in sinusoidal endothelial cells from both experimental groups when compared with controls. Lipopolysaccharide stimulated iNOS expression in sinusoidal endothelial cells from control livers only marginally, and from those with cirrhosis more strongly. There was no clear correlation between the amount of enzyme and nitrite formation. Cultured sinusoidal endothelial cells from livers with incipient cirrhosis showed a higher proliferative activity than controls. Endogenously-produced nitric oxide inhibited DNA synthesis in all groups in a cGMP-independent way. Exogenously-generated nitric oxide affected DNA synthesis differently in sinusoidal endothelial cells from controls and injured livers. CONCLUSION: The results provide evidence that cultured sinusoidal endothelial cells from controls and livers with incipient or advanced cirrhosis differ with respect to basal and lipopolysaccharide-stimulated nitrite production. The data can be taken as evidence that in sinusoidal endothelial cells from livers chronically injured by thioacetamide, eNOS and iNOS are aberrantly expressed and differently regulated.

High-dose megestrol acetate in the treatment of patients with ovarian cancer who have undergone previous treatment: Eastern Cooperative Oncology Group Study PD884.

High-dose megestrol acetate has been reported to be effective salvage therapy for women with ovarian carcinoma. The Eastern Cooperative Oncology Group performed this phase II study of oral megestrol acetate, 200 mg four times daily until disease progression, in 33 patients either with stage III or IV histologically confirmed ovarian carcinoma or with unresectable tumor in the pelvis with measurable or evaluable disease who progressed after treatment with one prior chemotherapy regimen. Thirty and 31 patients were evaluable for response and toxicity, respectively. No patient had an objective response and none had subjective improvement after a median treatment period of 1.4 months. Nausea or vomiting occurred in most patients, usually grade 1-2. Megestrol acetate is ineffective salvage therapy for patients with inoperable, previously treated ovarian carcinoma.

Phase II study of mitoguazone, cyclophosphamide, doxorubicin, vincristine and prednisone for patients with diffuse histologic subtypes of non-Hodgkin's lymphoma: an Eastern Cooperative Oncology Group Study (PE481).

Mitoguazone, an investigational agent with significant activity in advanced lymphoma, was added to a modified CHOP regimen (COPA) in an effort to improve the activity of standard therapy in 66 previously untreated patients with stages II-IV lymphoma and diffuse histology of intermediate or high grade other than lymphoblastic in this phase II pilot study. The regimen was well tolerated and the complete response rate in diffuse large cell lymphoma was 55%. Sixty-five percent of all complete responders were in complete response for at least one year. Despite these excellent results. it is unlikely that the addition of mitoguazone improved results compared with those obtained with standard therapy alone, since similar results have been frequently reported with the latter.

Cytokine patterns in patients who undergo hemofiltration for treatment of multiple organ failure.

The excessive uncontrolled activation of inflammatory cells and mediators after trauma or major surgery plays a key role in the development of adult respiratory distress syndrome and multiple organ system failure (MOSF). In the past elevated cytokine levels were shown to influence the outcome of these patients adversely. There are diverging results regarding the removal of circulating cytokines by various methods of hemopurification for clinical improvement of MOSF. Seven patients after trauma or major surgery underwent continuous venovenous hemofiltration (CVVH) for the treatment of severe organ failure of the heart and lungs (Murray score 2.74) but not for renal or liver failure. The cytokine levels were measured at the beginning and 15, 60, 120, and 240 minutes after initiation of CVVH (measure points MP1-5). Clinical improvement during the treatment was monitored, and correlation with cytokine levels was evaluated. Arterially measured tumor necrosis factor alpha rose from 11.14 ng/ml to 17.86 ng/m1 (p < 0.05). Arterial interleukin-6 (IL-6) levels significantly decreased during CVVH from 1284.7 ng/m1 to 557.9 ng/m1; IL-8 levels simultaneously decreased from an initial peak of up to 154.4 ng/m1 at MP3 to 97.3 ng/m1 at MP5. The drop in serum IL-6 and IL-8 levels closely correlated with clinical improvement. After 2 hours of CVVH the hemodynamic situation improved significantly, as revealed by a decrease in catecholamine expenditure, an increase in arterial pressure, and a decrease in pulmonary artery pressure. Moreover, 2 hours after the initiation of CVVH the oxygenation index rose significantly and correlated well with the drop in shunt fraction. The Murray score significantly fell to 1.86. The removal of IL-6 and IL-8 by CVVH after initial stimulation correlates with clinical improvement, which was demonstrated by significantly improved oxygenation and hemodynamics from 2 hours after the initiation of CVVH onward. The elimination of cytokines and several mediators by CVVH may contribute to the cardiopulmonary improvement of critically ill patients. In comparison with the clinical control group (n = 7), which was comparable in terms of MOSF, no intervention led to a similar improvement in cardiorespiratory failure, and overall two of these patients died. Moreover, patients of the control group experienced a significant longer stay at in the intensive care unit.

Nonparasitic cysts of the liver: results and options of surgical treatment.

Nonparasitic cysts of the liver (NPHC) are highly variable in respect to appearance and therapeutic approach. The treatment of these cysts varies according to the nature and appearance of the disease. Based on the variable nature of disease and the various therapeutic options, all of which were attempted in our patients, the most suitable mode of treatment for different forms of NPHC are discussed. Ninety-one patients with NPHC who had been treated surgically from 1977 through 1995 were examined retrospectively. Asymptomatic peripheral cysts measuring up to 10 cm do not require further treatment. Computed tomography (CT)-guided aspiration (n = 9) should be regarded as a palliative measure. Within a short period, CT-guided aspiration led to recurrence of symptoms in seven of our patients. Standard treatment of NPHC is fenestration with widest possible excision of the cystic wall, which can be performed laparoscopically (n = 10) or by the conventional surgical mode (n = 54). One patient was initially operated by the laparoscopic technique but developed bleeding, which necessitated conversion to the open mode. Three patients underwent synchronous laparoscopic cholecystectomy. Recurrence rates were similar: 11% in the laparoscopically treated group and 13% in the group that underwent conventional open surgery. Conventional surgical treatment was always successful in cases of solitary cysts. However, in cases of multiple cysts measuring more than 5 cm, conventional surgery was followed by recurrence of symptoms in 26% of patients (7/27), who then had to undergo a second operation. Partial resection of the liver (n = 9) was successfully performed in cases of polycystic disease (n = 5) with concomitant enlargement of the organ as well as in cases of large solitary cysts of the left lobe of the liver (n = 4). In patients in whom we found that the cysts communicated with the ductal system (n = 3), we performed a cystojejunostomy to drain the bile. The complication rate was low. In addition to frequent postoperative ascites, which necessitated no further intervention, we observed infectious complications in four patients. Twenty patients (22%) expired during a mean follow-up period of 6.2 years. Interestingly, deaths were frequently associated with malignancy (11/20). After fenestration of multiple cysts measuring > 5 cm, the patients are at high risk for recurrence. Hence partial resection of the liver is an excellent therapeutic alternative in selected patients with polycystic disease and massive enlargement of the organ in whom the disease could not be controlled by simple fenestration. The results of this study show that laparoscopic fenestration should replace the conventional surgical technique as the gold standard in cases of NPHC because the laparoscopic technique is less stressful for the patient and is associated with a rate of success similar to that of the conventional technique.

Macrophages from rat livers with micronodular and macronodular cirrhosis differ with respect to mediator release and DNA-synthesis.

BACKGROUND/AIMS: Liver macrophages play an essential role in necro-inflammatory liver damage which leads to fibrosis and cirrhosis. The aim of the present study was to compare the mediator release and the DNA synthesis of macrophages at an early and at a later stage of liver cirrhosis induced by thioacetamide. METHODS: Liver macrophages were isolated by an enzymic digestion method, followed by elutriation. The release of reactive oxygen species and cytokines, and the synthesis of DNA were measured in cultivated cells. RESULTS: The vitality of isolated macrophages from cirrhotic livers was always higher than 98%. The total yield of macrophages was less in micronodular cirrhotic livers and was markedly higher in macronodular cirrhotic livers when compared with age-matched controls. The cellular granules measured by sideward light scattering showed a shift to larger sizes in macrophages from micronodular cirrhotic livers when compared with the controls and the other experimental group. Macrophages from both cirrhosis groups exhibited a markedly higher unstimulated and lipopolysaccharide-stimulated IL-6 production than the controls. The release of TNF-alpha did not differ between controls and the experimental groups. Macrophages from macronodular cirrhotic livers produced higher amounts of nitric oxide but less superoxide anion radicals than the controls. DNA synthesis was 10-12-fold and 3-10-fold higher in macrophages from micronodular and macronodular cirrhotic livers, respectively, when compared with the age-matched controls. CONCLUSIONS: The data presented provide evidence that it is possible to isolate and to cultivate macrophages from livers with high yield and vitality at different stages of cirrhogenesis. Our results clearly demonstrate functional differences between macrophages from livers with micro- or macronodular cirrhosis; this finding may be important for the pathogenesis or perpetuation of the cirrhogenetic process.

Vascular reconstruction for limb salvage in sarcoma of the lower extremity.

OBJECTIVES: To examine the patency and limb-salvage characteristics of vascular reconstruction in patients with sarcomas of the lower extremity who had been treated with limb-preserving resection and to examine patient survival during a long follow-up period. DESIGN: Retrospective cohort study. SETTING: University hospital, tertiary referral center. PATIENTS: From 1984 to 1992, 14 patients underwent limb-preserving resection of sarcomas in the proximal lower extremity, with 20 vascular reconstructions performed. OUTCOME MEASURES: Color Doppler scans documented patency of the vascular reconstructions. Clinical evaluation included functional results in terms of limb movement and quality of life. Local tumor control and systemic recurrence were examined by repeated radiologic examination. Overall survival as well as time and cause of death were assessed. RESULTS: A total of 13 patients had patent vascular grafts, while the venous graft became occluded in 1 patient. Limb function was rated as excellent or good in 9 patients, as fair in 3, as poor in 1, and could not be clinically estimated in 1. Postoperative thrombosis of the venous graft was detected in 3 patients and was effectively managed by thrombectomy in 2. Three patients underwent reoperation because of hematoma or complications caused by local infection. The tumor endoprosthesis had to be replaced in 3 patients. During follow-up periods that ranged from 15 to 132 months (mean, 55 months), 4 patients died. In all of these patients the cause of death was systemic recurrence in the lung. Two additional patients developed pulmonary metastases, but at the time of this report, they were still alive as long as 132 months after operative resection or chemotherapy. No local recurrence was found. CONCLUSION: Limb-preserving resection of sarcoma of the lower extremity can be performed with satisfactory function of the limb maintained, even if it becomes necessary to resect the femoral vessels. Autologous venous graft for vascular reconstruction is the treatment of choice. In spite of the high incidence of metastases, considerable long-term survival is possible.

Oxygen radical formation, proliferative activity and phagocytic capacity of cultivated macrophages from cirrhotic rat livers.

A method to isolate and cultivate macrophages from Macronodular-cirrhotic rat livers was developed in order to characterize them biochemically, by comparing various functional parameters in macrophage cell cultures from controls and cirrhotic livers. Cells were prepared from female Wistar rats, made cirrhotic by treatment with thioacetamide, by means of a pronase-collagenase digestion method followed by a nycodenz gradient and elutriation. The yield of macrophages was 8.9 x 10(6) cells/g for controls and 10.6 x 10(6) cells/g for cirrhotic livers. The vitality of the cells was > 95%. Forty-eight hours after cultivation, the purity of the cell fractions amounted to 94% and 91% in controls and in the experimental group, respectively. Nitric oxide synthesis was more markedly stimulated by lipopolysaccharide (LPS) in cultures from cirrhotic livers than in those from controls (25 +/- 4 vs 5.8 +/- 1 nmol/10(6) cells/72 hours). Interferon-gamma (IFN-gamma) induced the nitric oxide synthase more rapidly in macrophage cultures from cirrhotic livers than in controls. The production of superoxide anions by macrophages from cirrhotic livers stimulated by zymosan was significantly lower by about 40% when compared with the controls. Incorporation of 3H-thymidine was increased to 250% in cultivated macrophages from thioacetamide-treated rats in comparison with macrophages from untreated animals. The stimulated phagocytic activity of cultivated macrophages from cirrhotic livers did not differ significantly from that of the controls. The data presented provide evidence that it is possible to isolate and to cultivate macrophages from macronodular-cirrhotic livers with high yield and vitality. They are characterized by enhanced proliferation, reduced formation of superoxide anions, and increased production of nitric oxide.

The transfer of interleukin-8 across the human placenta perfused in vitro.

OBJECTIVE: To assess the placental transfer of interleukin (IL)-8 in vitro. METHODS: Eighteen placentas obtained immediately after delivery were perfused with a mixture of 125I-labeled IL-8 (IL-8*) and unlabeled IL-8 in two different concentrations. Antipyrine was coinfused in all experiments as a reference compound. Fetal-to-maternal and maternal-to-fetal perfusions were performed. Radioactivity was measured in a gamma counter at the end of each perfusion experiment. In four experiments, unlabeled IL-8 was analyzed in addition to labeled IL-8 to exclude a change in the IL-8/IL-8* ratio resulting from membrane transfer. RESULTS: Two of the 18 experiments had to be discarded because of poor transfer of antipyrine. There was only faint accumulation of radioactivity in the transplacental compartment, regardless of whether the test substance was added maternally or fetally. Because measurement of unlabeled IL-8 yielded negative results, the radioactivity is clearly attributable to free iodine 125, which is generated during IL radiolabeling or which disassociates from IL-8 in small amounts after radiolabeling. CONCLUSION: Interleukin-8 does not appear to cross the placenta by simple diffusion, regardless of the concentration or the perfusion rate. The impermeability of the placenta to the diffusion of IL-8 might explain why there is insufficient correlation between serum and amniotic fluid cytokine concentrations of pregnant women and the presence of the amnion infection syndrome.

Phagocytic function and metabolite production in thioacetamide-induced liver cirrhosis: a comparative study in perfused livers and cultured Kupffer cells.

BACKGROUND/AIMS: The aim of the study presented here was to evaluate the basal and stimulated phagocytic activities and the metabolite production of isolated perfused livers, and also the phagocytic capacity of cultured Kupffer cells from rats with macronodular cirrhosis. METHODS: Rats were made cirrhotic by oral administration of thioacetamide. The phagocytic activity was assessed by the rate of removal of colloidal carbon. The Kupffer cells were prepared by a pronase/collagenase digestion method followed by elutriation. RESULTS: The phagocytic activity and production of glucose, lactate and pyruvate were reduced in cirrhotic livers when calculated per g liver. Due to hyperplastic-regenerative processes the mass of the cirrhotic livers was markedly augmented so that the colloidal carbon uptake calculated per cirrhotic liver was not significantly different from the controls. Colloidal carbon-induced glucose release increased more markedly in the controls than in cirrhotic livers. Isoproterenol considerably stimulated phagocytosis and glucose production in controls, whereas the response was clearly reduced in cirrhotic livers when calculated either per g liver or per total liver weight. The cyclic AMP analogue elicited a marked glycogenolytic response in the controls, whereas there was only a slight increase in glucose production in cirrhotic livers. Phagocytosis of cirrhotic livers was only moderately stimulated by opsonized zymosan when compared with the controls. Freshly isolated Kupffer cells exhibited a reduced phagocytic activity. Stimulation by zymosan was observed only in cell suspensions of the controls. In contrast, Kupffer cells from cirrhotic livers did not differ from controls with respect to basal or zymosan-stimulated phagocytic activity after 48-h cultivation. CONCLUSION: The stimulated phagocytic function was disturbed in perfused macronodular-cirrhotic livers as compared to controls. In contrast, 48-h cultured Kupffer cells from cirrhotic livers exhibited the same basal and stimulated phagocytic capacity as controls. The glucose release from perfused livers, initiated by stimulation of Kupffer cells or hepatocytes, was significantly reduced in cirrhotic livers. Therefore, we postulate an impaired intra- and/or intercellular signalling in macronodular-cirrhotic livers.

Randomized trial of initial therapy with melphalan versus cisplatin-based combination chemotherapy in patients with advanced ovarian carcinoma: initial and long term results--Eastern Cooperative Oncology Group Study E2878.

BACKGROUND: Following surgical debulking, most patients with international Federation of Gynecology and Obstetrics (FIGO) Stage III or IV carcinoma of the ovary receive treatment with combination chemotherapy. However, the optimal postsurgical therapy for ovarian carcinoma remains to be defined. METHODS: To define better the role of initial therapy with a cisplatin-based chemotherapy regimen, the Eastern (Cooperative Oncology Group (ECOG) initiated a randomized, Phase III trial, EST 2878, comparing initial therapy with a single, orally administered alkylating agent, melphalan, versus a complex regimen employing cyclophosphamide, hexamethylmelamine, doxorubicin, and cisplatin (CHAD). Women who failed treatment with melphalan were crossed-over to treatment with CHAD minus the cyclophosphamide (HAD). Study endpoints included response to therapy, time to treatment failure, and overall survival. RESULTS: Between October, 1978, and November, 1980, EST 2878 accrued 253 patients with advanced epithelial carcinoma of the ovary. There were 118 eligible patients initially treated with melphalan and 126 with CHAD. Two patients experienced lethal toxicities, including gastrointestinal hemorrhage (1 patient) and neutropenic sepsis (1 patient), and 22 patients experienced life-threatening toxicities, including hematologic toxicity (21 patients) and anaphylaxis (1 patient). Response to treatment and clinical complete response rates were higher in women receiving CHAD (60% and 38%, respectively) versus melphalan (42% and 21%, respectively) (P = 0.037 and P = 0.024, respectively), but these differences were confined to women older than 50 years of age. Likewise, time to treatment failure was significantly longer in women receiving CHAD (P = 0.014), but the difference was again confined to women older than 50 years of age and to women suboptimally debulked at the time of surgery. Survival did not differ between the two arms (median survivals of 17.5 months with initial melphalan therapy and 19.5 months with CHAD), probably because women treated initially with melphalan received salvage therapy with HAD). Twenty-three patients survived longer than 10 years. Among 18 long term survivors who had retrospective pathologic review, 8 had borderline tumors of the ovary. CONCLUSIONS: In women with advanced ovarian cancer, initial therapy with a cisplatin-based combination chemotherapy regimen resulted in higher clinical complete response rates and longer time to failure compared with initial therapy with a single, oral alkylating agent; however, the benefits of this approach were confined to women older than 50 years of age at diagnosis, and there was no significant difference in survival.

Natural atmospherics and occurrence of seizures in six adolescents with epilepsy: a cross correlation study.

As already seen in a former study of 315 epileptic seizures in adults, subsequent investigation of 3333 epileptic seizures in six adolescents revealed a significant increase of the seizure frequency during days with a higher mean frequency of 28 kHz atmospherics, and a decrease during days with a (Baumer apparatus) distinctly higher amount of 10 kHz when compared with the daily mean frequency within the whole period. However, one patient showed an opposite behaviour regarding the correlations of 28 and 10 kHz atmospherics and the mean numbers of seizures.

[Nonparasitic liver cysts. Overview of therapy with long-term results]. / Nicht-parasitäre Leberzysten. Therapieüberblick mit Langzeitergebnissen.

Symptomatic nonparasitic cysts of the liver require surgical intervention. Seventy-one patients were treated between 1977 and 1993 at the Department of General Surgery, University of Vienna. Different surgical treatments were compared with regard to complications and recurrence. Interventional puncture led to recurrences in nearly all cases and represents only a palliative procedure. Surgical treatment consisted of either laparoscopic (n = 7) or conventional (n = 44) fenestration or excision. The rates of recurrence did not differ significantly (14% vs 9%). The laparoscopic procedure is successful not only in polycystic disease but also in solitary cysts. Wide deroofing and excision were equally effective. Laparoscopic therapy should be tried in all cysts initially, because it causes less stress than celiotomy. Because of the small number of laparoscopically treated patients in the literature and in the authors' own experience, the significance of the difference in outcome between the two methods could not be established. In more patients, further investigations should be carried out to ascertain whether the laparoscopic method is superior regarding surgical stress and recurrence. Cystojejunostomy (n = 3) and hepatic resection (n = 2) are reserved for special indications. One homologous liver transplantation was successfully carried out 6 months after cystojejunostomy because of a cholangiocellular carcinoma. Frequent postoperative ascites represented a persistent problem in only one patient. Two of three cases of postoperative infection with intraabdominal abscesses led to death. Altogether, 16 patients died, including seven because of malignancy and three because of septic complications of a Potter III syndrome.