Detection of K(ATP) channels subunits in human term placental explants and evaluation of their implication in human placental lactogen (hPL) and human chorionic gonadotropin (hCG) release.

INTRODUCTION: ATP-sensitive potassium channels (KATP channels) have been identified in a variety of tissues. Nevertheless, the presence and role of such metabolism-sensitive K+ channels still remain to be unraveled in the reproductive system. METHODS: The study evaluates the presence of KATP channel subunits in human term placental explants by immunohistochemistry, proximity ligation assay, Western blot and RT-PCR techniques. The potential involvement of KATP channels in human placental lactogen (hPL) and human chorionic gonadotrophin (hCG) release has been assessed radioimmunologically from human term placental explants incubated in the presence of different KATP channel modulators. RESULTS: Immunolocalization of the KATP channel subunits documented both the Kir6.2 and SUR2 subunits in the syncytiotrophoblast of human term placenta. Their colocalization was demonstrated by proximity ligation assay and their presence was further confirmed by immunoblotting and RT-PCR. Kir6.1 subunit was immunolocalized in blood vessels media. SUR1 was not expressed at the mRNA level. Incubation of human term placental explants in the presence of increasing concentrations of modulators of KATP channels such as glibenclamide, tolbutamide, pinacidil or diazoxide did not affect the measured hCG and hPL secretory rates. DISCUSSION: Our study reports, for the first time, the presence of the KATP channel subunits Kir6.2 and SUR2 in the human term syncytiotrophoblast. However, under the present experimental conditions, the activation or inhibition of these putative KATP channels by different pharmacological agents did not affect the hPL and hCG secretory rate of human term placental explants. CONCLUSION: The present findings suggest that the human term syncytiotrophoblast might be endowed with KATP channels. Further studies should clarify their implication in the syncytiotrophoblast ionic homeostasis and hormone regulation.

[The c-erbB-related oncoproteins in normal placenta and in gestational trophoblastic diseases (in vitro study)]. / A c-erbB családba tartozó onkofehérjék normális lepényben és terhességi trophoblast-betegségekben (in vitro vizsgálatok).

In this study the expression of epidermal growth factor receptor (EGFR) and c-erbB-2, c-erbB-3 and c-erbB-4 oncogenes were investigated in gestational trophoblastic diseases and normal first trimester placenta. Furthermore, the possibility that macrophage (IL-1 alpha, IL-1 beta, TNF) and lymphocyte (IL-2, gamma-IFN, GM-CSF) cytokines effects are mediated by changes in EGFR expression were studied. Paraffin sections of 16 cases of partial mole, 25 cases of complete mole, 10 cases of gestational choriocarcinoma and 11 cases of therapeutic abortion were studied immunohistochemically for EGFR, c-erbB-2, c-erbB-3 and c-erbB-4 proteins. The presence of EGFR mRNA was studied using in situ hybridization. JEG-3 human choriocarcinoma cells were incubated with varying concentrations of interleukin 1-alpha, interleukin 1-beta, interleukin 2, gamma-interferon, granulocyte-macrophage colony stimulating factor and tumor necrosis factor-alpha, and the expression of EGFR was measured by radioimmunoassay using a murine monoclonal antibody with specificity for EGFR. Staining for EGFR was detected immunohistochemically in all cell type in gestational trophoblastic diseases and normal placenta. The levels of expression of EGFR in choriocarcinoma and syncytiotrophoblasts and cytotrophoblasts in complete mole were significantly greater than those in syncytiotrophoblasts and cytotrophoblasts in both normal placenta and partial mole (p < 0.01, p < 0.01). The immunoreactivity of c-erbB-2 was significantly stronger in choriocarcinoma and extravillous trophoblast in complete mole than that in extravillous trophoblast in partial mole and normal placenta (p < 0.02, p < 0.01, respectively). Strong immunostaining for EGFR (p = 0.02) and c-erbB-3 (p < 0.01) in extravillous trophoblasts of complete mole was found to be significantly correlated with the development of persistent postmolar gestational trophoblastic tumor. Macrophage-derived cytokines IL-1 alpha, IL-1 beta and TNF significantly suppressed cell growth; this was associated with a significant increase in EGFR expression. The lymphocyte (IL-2, gamma-IFN, GM-CSF) cytokines had no significant effect on either EGFR expression or cell growth. These findings support the concept that cytokines may act as paracrine mediators of autocrine processes involved in choriocarcinoma cell growth regulation by modulating growth factor receptor expression. The EGFR-related family of oncogenes may be important in the pathogenesis and prognosis of gestational trophoblastic diseases.

Comparison of 4 analgesic agents for venipuncture.

This study compared pain on application, pain on venipuncture, cost, and convenience of 4 analgesic agents used for venipuncture. A convenience sample of 280 preoperative subjects was assigned randomly to 1 of 4 groups. Group 1 received 2.5% lidocaine--2.5% prilocaine cream (LPC) topically, Group 2 received dichlorotetrafluoroethane spray (DCTF), Group 3 received 0.5% lidocaine subcutaneously, and group 4 received normal saline with 0.9% benzyl alcohol (BA) subcutaneously. A 7-point verbal descriptor scale measured pain on application, and a 100-mm visual analogue scale measured pain on venipuncture. Cost was measured and compared on unit-dose basis. Convenience was measured with a questionnaire survey completed by the investigators. There was no significant difference (P < .05) among the groups for age, sex, ASA physical status, or difficulty of venipuncture. There was a significant difference in pain on application for all 4 agents (P < .05). The DCTF had the highest pain on application score (1.7 +/- 0.1), while the LPC had no pain on application (0.0 +/- 0). Lidocaine had a higher pain on application score (1.08 +/- 0.1) than the BA (0.52 +/- 0.1) but a lower score than DCTF. Lidocaine (1.3 +/- 0.3) was significantly less painful (P < .05) on venipuncture than LPC (2.18 +/- 0.3) and DCTF (2.5 +/- 0.3) but was not significantly different than BA (1.92 +/- 0.3). (All scores are given as mean +/- SEM.) There was a significant difference in cost and convenience among the 4 agents, with BA and lidocaine being the least expensive analgesic agents. Lidocaine, DCTF, and BA were equally convenient to use, while LPC was the least convenient, (P < .05). Lidocaine had low pain on venipuncture and low cost and convenience of use, but it was less than ideal in terms of pain on application. The BA had all the qualities of an ideal analgesic agent for venipuncture in this sample and should be considered as an analgesic agent for venipuncture.

Expression of epidermal growth factor receptor-related family products in gestational trophoblastic diseases and normal placenta and its relationship with development of postmolar tumor.

OBJECTIVE: The goal of this work was to study the expression of epidermal growth factor receptor (EGFR) and c-erbB-3 and c-erbB-4 oncogenes in gestational trophoblastic diseases and normal first-trimester placenta. STUDY DESIGN: Paraffin sections of 16 cases of partial mole, 25 cases of complete mole, 10 cases of gestational choriocarcinoma, and 11 cases of therapeutic abortion were studied immunohistochemically for EGFR, c-erbB-3, and c-erbB-4 proteins. The presence of EGFR mRNA was studied using in situ hybridization. RESULTS: Staining for EGFR was detected immunohistochemically in all cell types in gestational trophoblastic diseases and normal placenta. In situ hybridization for EGFR mRNA correlated with immunostaining for EGFR in all tissues studied. All 10 cases of choriocarcinoma exhibited strong immunoreactivity for EGFR. The levels of expression of EGFR in choriocarcinoma and syncytiotrophoblasts and cytotrophoblasts in complete mole were significantly greater than those in syncytiotrophoblasts and cytotrophoblasts in both normal placenta and partial mole (P < 0.01, P < 0.01). Expression of c-erbB-3 did not significantly differ among placental and gestational trophoblastic disease tissues and trophoblastic cell types except for significantly increased expression in choriocarcinoma as compared with cytotrophoblasts of partial mole (P = 0.02). The placenta, complete and partial mole, and choriocarcinoma tissues demonstrated similar immunoreactivity for c-erbB-4. Strong immunostaining for EGFR (P = 0.02) and c-erbB-3 (P < 0.01) in extravillous trophoblasts of complete mole was found to be significantly correlated with the development of persistent postmolar gestational trophoblastic tumor. CONCLUSION: The EGFR-related family of oncogenes may be important in the pathogenesis of gestational trophoblastic diseases. The increased expression of EGFR and c-erbB-3 in complete mole may also influence the development of persistent gestational trophoblastic tumor.

Differential gene expression pattern between normal human trophoblast and choriocarcinoma cell lines: downregulation of heat shock protein-27 in choriocarcinoma in vitro and in vivo.

OBJECTIVE: Our purpose was to identify potential differences in gene expression between normal trophoblast and choriocarcinoma cells. METHODS: The Atlas human cDNA expression array hybridization technique was used to study the gene expression pattern in normal trophoblast and choriocarcinoma cell lines. Furthermore, to confirm heat shock protein-27 (Hsp-27) expression data, reverse transcriptase-PCR (RT-PCR), Western blot, and immunohistochemical analyses were used in vitro with cell lines and in vivo with paraffin sections. RESULTS: The expression of nine genes was strongly different comparing a normal trophoblast cell line with choriocarcinoma cells on the Atlas membranes. Compared to normal trophoblast cells, six genes were upregulated and three were downregulated in choriocarcinoma cells. Furthermore, the downregulation of Hsp-27 in choriocarcinoma cells was confirmed both in vitro with cell lines and in vivo with paraffin sections using RT-PCR, Western blot, and immunohistochemical techniques. CONCLUSION: cDNA expression array is a useful technique for identifying differentially expressed gene patterns in normal trophoblast and choriocarcinoma cells. The strong expression of Hsp-27 in placental villous trophoblast cells may play a role in trophoblast differentiation. The downregulation of Hsp-27 in choriocarcinoma may contribute to the extreme sensitivity of trophoblastic tumors to chemotherapy.

Matrix metalloproteinases and their inhibitors in gestational trophoblastic diseases and normal placenta.

OBJECTIVE: Our purpose was to investigate the expression of matrix metalloproteinases (MMPs) in gestational trophoblastic diseases and normal first-trimester placenta. METHODS: Paraffin sections of 16 partial moles, 25 complete moles, 10 gestational choriocarcinomas, and 11 normal first-trimester placentas were studied immunohistochemically for expression of MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, and tissue inhibitor of metalloproteinase-1 (TIMP-1). RESULTS: Nine (90.0%) of the choriocarcinoma cases showed strong intensity of staining for MMP-1. Choriocarcinoma exhibited significantly stronger staining for MMP-1 than syncytiotrophoblast in normal placenta (P < 0.01), partial mole (P < 0.01), and complete mole (P < 0.01). Choriocarcinoma also showed significantly stronger staining for MMP-1 than the extravillous trophoblast in placenta (P < 0.05). MMP-2 was expressed only in syncytio- and extravillous trophoblasts in normal placenta, partial mole, and complete mole. Choriocarcinoma and the extravillous trophoblast in partial mole and complete mole had significantly stronger staining for MMP-2 than the extravillous trophoblast in placenta (P < 0.05, P < 0.01, P < 0.01, respectively). Choriocarcinoma also exhibited significantly stronger staining for MMP-2 than syncytiotrophoblasts in placenta (P < 0.01), partial mole (P = 0.05), and complete mole (P < 0.01). The expression of MMP-3, MMP-9, and MMP-13 was similar in all four tissues with the predominance of syncytiotrophoblast for MMP-3 and MMP-13 and cytotrophoblast for MMP-9. While 8 (73.0%) placentas, 14 (87.5%) partial moles, and 19 (76.0%) complete moles showed strong immunoreactivity for TIMP-1 in syncytiotrophoblasts, no strong staining was found in choriocarcinomas (P < 0.01, P < 0.01, P < 0.01, respectively). CONCLUSION: The extravillous trophoblast of first-trimester placenta has significantly less expression of MMP-1 than choriocarcinoma and significantly less expression of MMP-2 than choriocarcinoma and extravillous trophoblast of partial and complete mole. The expression of TIMP-1 was significantly less in choriocarcinoma than the syncytiotrophoblast of normal placenta, partial mole, and complete mole. MMPs and their inhibitors may play a role in the pathogenesis of gestational trophoblastic diseases.

Thrombolysis is superior to heparin for non-obstructive mitral mechanical valve thrombosis.

BACKGROUND AND AIM OF THE STUDY: Non-obstructive prosthetic valve thrombosis (PVT) is a unique subset that features clinical presentation without heart failure, and may be asymptomatic. Thrombolysis has been accepted for obstructive PVT, but treatment strategies of non-obstructive PVT are controversial. This study compared the efficacy and safety of thrombolysis and heparin treatment in these patients. METHODS: Between 1993 and 1998, 20 consecutive patients were found by multiplane transesophageal echocardiography (TEE) to have non-obstructive PVT. TEE was performed for peripheral embolism in two patients, stroke or transient ischemic attack in six, stroke and fever in two, fever in one patient, as a routine postoperative examination in two patients, and for other reasons in seven. Patients were allocated to two groups: group I (n = 8) received streptokinase-mediated fibrinolysis; group II (n = 12) received intravenous heparin by infusion. Treatment was monitored using TEE. RESULTS: There was no difference between patient groups with regard to sex, age, type of prosthesis and time since operation, though anticoagulant status was more often inadequate in group II. By TEE, valve motion was normal in all patients. In group I, all thrombi were mobile and 5-13 mm in diameter; in group II, all thrombi but three were mobile and 3-18 mm in diameter. In group I, thrombolysis was successful in all patients, without complications, within 6-72 h. In group II, heparin treatment was successful in six patients in 3-32 days. In one patient, seven days' of unsuccessful heparin was followed by two months' successful coumarin therapy. Among five unsuccessful cases, the thrombus size increased in four (three became obstructive in 7-35 days); all four patients were switched to fibrinolysis, which was successful without complications in 12-60 h. The fifth patient developed a stroke after nine days of heparin treatment and was subsequently operated on. CONCLUSIONS: Non-obstructive PVT may be asymptomatic in one-third of patients. Thrombolysis is an efficient and safe treatment, and may be first-line therapy if there is no contraindication. Heparin treatment was successful in about one-half of our cases in the presence of sessile or small thrombi and inadequate anticoagulant status. In unsuccessful cases, thrombi became obstructive or caused stroke during heparin therapy, the adequate duration of which remains unclear.

[The role of echocardiography in acute myocardial infarct]. / Az echocardiographia szerepe akut myocardialis infarctusban.

Echocardiography performed in acute myocardial infarction helps to make the diagnosis, to detect complications of acute myocardial infarction and to choose adequate therapy. The authors evaluate the echocardiographic results of 47 patients at bedside exam. Wall motion abnormalities were revealed in 16 of 19 Q-infarct cases. Echocardiography performed in 28 suspected cases of myocardial infarction showed segmental wall motion abnormalities in 14 cases, out of them infarction was diagnosed later in 9 patient and non-Q myocardial infarction in 3 cases. Heparin was given in all cases, but thrombolysis was applied in only 9 patients. Left ventricular thrombus was found in 3 patients with anterior myocardial infarction, neither of whom had received thrombolytic therapy. The following mechanical complications were detected: free wall rupture in one patient, ventricular septal defect in three patients, early left ventricular aneurysm in one patients and right ventricular infarction in one patient. 14 patients with decreased left ventricular function were not subsequently given beta receptor blockers.

[Management of early avascular femur head necrosis by implantation of a muscle-bone graft]. / A korai avascularis combfejnecrosis kezelése izomlebenyes csont beültetéssel.

Authors describe the results of 10 patients operated for avascular necrosis of the femoral head. The first operation was performed in October 1987. The follow-up was in average 41.9 (24-54) months, minimally 2 years. 7 patients improved, 2 deteriorated, 1 was unchanged. The analysis of the results showed that this operation is indicated only in strictly stated conditions.

[Treatment of carcinoid syndrome with a somatostatin analogue]. / Carcinoid szindróma kezelése somatostatin analoggal.

Octreotide, a long-acting somatostatin analogue has recently been introduced in the therapy of gastroenteropancreatic endocrine tumors, but home experience has been lacking. With the aim of drawing attention to this therapeutic possibility, a case of malignant carcinoid syndrome treated with octreotide for 18 months is reported. Despite the therapeutic attempts preceding the octreotide administration a gradual progression in clinical symptoms was observed and cardiac failure due to fibrotic and valvular heart disease developed. Cytotoxic chemotherapy, serotonin antagonists or repeated selective embolisation of the hepatic artery only resulted in a short transitional improvement. Octreotide in a dose of 100 micrograms three times daily by subcutaneous injection provided effective and rapid relief from episodic flushing and serious diarrhoea. Plasma level of serotonin and 24-hour urinary excretion of 5-hydroxyindolacetic acid decreased from 6 micrograms/ml to 2 micrograms/ml and from 800 mumol/day to 70 mumol/day, respectively. No changes in the number and extension of liver metastases could be seen after introducing the octreotide treatment. The patient's compensated cardiac status could be preserved and continuous therapy provided an acceptable quality of life.

[Use of a tumor prosthesis in the management of complications from a Guepar-type knee prosthesis]. / Guepar típusú térd protézis szövõdményének ellátása tumor protézissel.

In the operative treatment of the knee diseases Guepar prosthesis was used formerly more frequently, presently however only rarely. The frequence of complications and their treatment are many times serious problems. Authors describe one case in which the postoperative supracondylaer fracture necessitated the insertion of a special knee prosthesis.

[Delayed results of Wiltse's operation in the management of spondylolisthesis]. / A Wiltse-mütét késöi eredményei a spondylolisthesis kezelésében.

Wiltse's spondylodesis was performed in 111 patients in the Department of Orthopaedics, National Institute for Rhelvmatology and Physiotherapy between 1978-1982. 58 of them were reexamined by the authorsclinically and radiologically more than 5 years after the operation. In 47 of the 58 patients good or adequate clinical results were found whereas in 43 cases the development of bone bridge could be observed. Attention is called to the good operative indication and the exact operative technique.

[A case of surgically treated septum perforation associated with acute myocardial infarct]. / Acut myocardialis infarctushoz társuló septum perforatio operált esete.

The authors present the case-history of an elderly female patient with acute myocardial infarction complicated by ventricular septal defect (VSD). She was operated on in order the VSD to be corrected but--probably because of sutural insufficiency--it temporarily reopened, later closed spontaneously. The significance of certain tests in the differential diagnosis of systolic murmur after acute myocardial infarction is discussed, and the importance of these findings compared to the clinical picture is emphasized.

[Experience with Cefobid in severe infections complicating immunodeficiency diseases]. / Cefobiddal szerzett tapasztalatok immundeficiens haematologiai betegek súlyos fertözéseiben.

As a 3rd generation cephalosporin Cefobid monotherapy was applied during 1985-1986 with 16 hematological patients in immunodeficient, immunosuppressive states where the available aimed and combined antibiotic therapy failed to be effective for the treatment of bacterial infections of grave course and septic character. 4 g/day was the average I.V. dose of Cefobid, higher doses were applied only in especially grave septic states. The hematological patients tolerated well the Cefobid in monotherapy. Recovery form the septic state and excellent clinical effect was found with 9 patients, good effect with 4 and satisfactory effect with 1 patient. In 1 case the therapy had to be stopped owing to drug hypersensitivity. Cefobid is regarded as an antibiotic drug that is effective if used in monotherapy for treating grave, septic infections of hematological patients in immunodeficient--immunosuppressive--myelodepressive states having received earlier antineoplasmic polychemotherapy.

[Successful surgical management of rupture of the papillary muscle diagnosed by ultrasound]. / Ultrahanggal felismert papillaris izomruptura sikeres mütéti megoldása.

The rupture of the papillary muscle is an infrequent complication of myocardial infarction. Survival of the acute phase depends on the severity of the rupture and the remaining function of the left ventricle. Permanent survival may be ensured however only by surgical intervention. The authors present the case record of a patients whose disease in connection with a myocardial infarction was revealed by echocardiography and was operated on successfully. No such data were found in the Hungarian literature.

Incidence of Mycoplasma hominis and Ureaplasma urealyticum infection in pregnant women and gynaecological patients; the effectivity of doxycycline therapy.

The authors report on the results of Mycoplasma hominis and Ureaplasma urealyticum cultivations performed within two and a half years in 1,421 pregnant women and gynaecological patients. Considering the obstetrical-gynaecological patients Mycoplasma hominis was identified in 7.25% and Ureaplasma urealyticum in 38.11% of cases. No significant difference was found in the incidence of Mycoplasma infection when comparing the results of cultivations of samples obtained from a clinically non-inflamed vagina or cervix with the results of cultivations of samples obtained from the female lower genital tract in the course of an inflammatory disease. In cases of endometritis, salpingitis or cophoritis Mycoplasma hominis could be isolated from the cervix significantly more frequently. The incidence of Mycoplasma hominis infection was also significantly higher in the examined 315 sterile women. The incidence of Mycoplasma hominis and Ureaplasma urealyticum infection did not differ when comparing the 267 symptom-free pregnant women to the other patients. The presence of the pathogenic organisms did not aggravate the unfavourable course of pregnancy. When examining the effectivity of Doxycycline capsule the drug proved to be effective in 78 patients for the treatment of genital Mycoplasma infections.

Transpancreatic catheterization of the right hepatic artery for chemoembolization using a new infusion system.

The right hepatic artery was catheterized for chemoembolization in a patient with liver-dominant metastatic breast carcinoma and occlusion of the celiac artery by tumor compression. This was accomplished by use of a new coaxial infusion catheter-steerable guidewire system passed through the superior mesenteric artery and posterior pancreatic arcade.