[Uterine myomatosis with senile hematometra in a 101-year-old patient]. / Uterus myomatosus mit seniler Hämatometra bei einer 101-jährigen Patientin.

A 101-year-old patient presented with uterine myomatosis and bleeding associated with a large hematometra. An abdominal hysterectomy with adnexectomy was performed following an in-depth consultation with the patient and her daughter. The patient was discharged on the 12(th) postoperative day after a complication-free course. This case report demonstrates not only the current possibilities in the gynecological treatment of very old patients but also the hidden reserves in the gynecological care ot these women.

Excretion of low molecular weight heparin in human milk.

AIMS: The excretion of low molecular weight heparin (LMWH) in breast milk was investigated in 15 lactating mothers after Caesarean section. METHODS: Blood and milk samples were collected before and 3-4 h after once daily routine subcutaneous injection of 2500 IU dalteparin. Anti-Xa activity was measured by an assay utilizing prolonged clotting times in plasma or breast milk as an index of LMWH activity. RESULTS: Plasma anti-Xa activities ranged from 0.074 to 0.308 IU ml(-1) of plasma. Anti-Xa activities in breast milk ranged from < 0.005-0.037 IU ml(-1) of milk. This is equivalent to a milk/plasma ratio of < 0.025-0.224. CONCLUSIONS: Therefore, it appears highly unlikely that puerperal thromboprophylaxis with LMWH has any clinically relevant effect on the nursing infant.

Deliberate self-harm patients who leave the accident and emergency department without a psychiatric assessment: a neglected population at risk of suicide.

OBJECTIVES: Deliberate self-harm (DSH) patients, despite their risk of suicide, are often discharged directly from accident and emergency (A&E) departments without undergoing a psychiatric assessment. The aims of this study were to determine the characteristics and outcome of these patients. METHODS: The characteristics of DSH patients who were discharged directly from an A&E department over a 2-year period were investigated, comparing those who had a psychiatric assessment with those who did not. In a matched control design, the outcome of a group of patients who did not receive a psychiatric assessment was compared with that of a group of patients who were assessed. RESULTS: Of DSH patients who were discharged directly from the A&E department 58.9% (145/246) did not have a psychiatric assessment. Nonassessed patients were more likely to have a past history of DSH, to be in the 20-34 year age group, and to have exhibited difficult behaviour in the A&E department. Patients presenting between 5 p.m. and 9 a.m. were less likely to be assessed than those attending between 9 a.m. and 5 p.m. Further DSH during the subsequent year occurred in 37.5% of the nonassessed patients compared with 18.2% of matched assessed patients. They were also more likely to have psychiatric treatment. CONCLUSION: A substantial proportion of DSH patients discharged directly from A&E departments do not receive a psychiatric assessment. Nonassessed patients may be at greater risk of further DSH and completed suicide than those who are assessed. Hospital services need to be organised such that DSH patients managed in A&E departments can receive an assessment of psychosocial problems and risk.

Cripto-1-induced increase in vimentin expression is associated with enhanced migration of human Caski cervical carcinoma cells.

Cripto-1 (CR-1), a member of the EGF-CFC peptide family, plays an essential role during mesoderm formation in vertebrates as well as in cancer development. Using cDNA gene expression array, Western blot, and indirect immunofluorescence, an increase in vimentin expression was demonstrated in CR-1-transfected human Caski cervical carcinoma cells compared to control vector-transfected cells. In parental Caski cells, recombinant CR-1 induced a dose-dependent increase of vimentin protein expression within 24 h. Since vimentin expression has been demonstrated to correlate with a more aggressive phenotype in human cervical cancer, the migration capacity of CR-1-transfected or CR-1-treated Caski cells was studied in the Boyden chamber assay. Compared to the vector-transfected or untreated Caski cells, CR-1-transfected cells or cells treated with recombinant CR-1 exhibit enhanced migration, both through collagen- and through gelatin-coated membranes. Additionally, CR-1 can function as a chemoattractant for Caski cells. These findings are of biological significance since CR-1 is overexpressed in several types of human carcinomas. The present data demonstrate that CR-1 can increase vimentin expression and modulate migration in human cervical carcinoma cells.

Expression and function of EGF-related peptides and their receptors in gynecological cancer--from basic science to therapy.

EGF-related peptides and their receptors play an important, but not fully understood role, both, in epithelial physiology and pathophysiology but also in human tumor carcinogenesis and tumor behavior, respectively. Overexpression of EGF-related growth factors from normal epithelium to carcinomas has been demonstrated for several human tissues such as breast, endometrium, cervix and ovary. Additionally, the differential overexpression of EGFR or erb B-2 in various malignancies has already proven to be efficacious in stratifying patients with respect to a poor prognosis. These data suggest that EGF-related growth factors, erb B receptors or signaling proteins that function either upstream or downstream from these receptors may represent novel targets for selective tumor therapy. In the future, conventional chemotherapy regimes will ultimately be wedded to more biologically-oriented therapies. One important target for these novel therapeutic approaches in solid tumors will be the EGF-related growth factors and their receptors.

Kinetic studies on rabbit liver glucocorticoid 5alpha-reductase.

The serum concentration of active glucocorticosteroids depends not only on adrenal synthesis but also on enzymatic activation of 11-dehydro-glucocorticoids in the liver by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). In order to define the respective involvement of other regulative enzymes in the metabolism of 11-dehydro-glucocorticoids in the liver, the objective of this study was to evaluate the kinetic behavior of NADPH:delta 4-3-ketosteroid-5alpha-reductase (5alpha-reductase, EC 1.3.99.5). The interrelations to liver 11beta-HSD1 will be discussed. The kinetic properties of 5alpha-reductase of the rabbit liver were measured by a radioenzymatic assay and characterized with respect to protein-, substrate-, cosubstrate-, and pH-dependence. Michaelis-Menten enzyme kinetic parameters (Km and Vmax) were obtained for the formation of 5alpha-reduced 11-dehydrocorticosterone and corticosterone metabolites. We found that both 11-dehydrocorticosterone (Km 4.2 x 10(-6) mol/l, Vmax 2,600 pmol x min(-1) x mg(-1)) and corticosterone (Km 0.5 x 10(-6) mol/l, Vmax 38 pmol x min(-1) x mg(-1)) exhibit a high affinity to 5alpha-reductase. With respect to cosubstrate-, pH-dependence and finasteride inhibition, it is likely that 11-dehydrocorticosterone metabolism is primarily controlled by isoenzyme 5alpha-reductase type 1. This study shows that the deactivation of GCS especially of 11-dehydro-glucocorticoids via 5alpha-reductase is an important metabolic pathway in the liver. The metabolic activation of GCS by 11beta-HSD could possibly lead to an excess of GCS in the hepatocytes. Due to 5alpha-reductase activity this excess can be limited - on the level of CORT as well as of 11-DHC.

Effect of dexamethasone, triiodothyronine and dimethyl-isopropyl-thyronine on lung maturation of the fetal rat lung.

Our purpose was to elucidate why clinical studies have up to now failed to demonstrate a positive effect of TRH combined with glucocorticosteroids on fetal lung maturity. Morphological and biochemical lung maturation were determined by electron microscopy, choline incorporation, and surfactant-protein-A m-RNA synthesis in rat lung organoid cultures after exposure with a series of concentrations of dexamethasone, triiodothyronine, and dimethyl-isopropyl-thyronine. Thyroid hormones improved morphogenesis of lung histotypic structures but had a negative effect on surfactant synthesis whereas glucocorticosteroids had a positive effect on the surfactant synthesis but a negative effect on morphogenesis. The combination of both substances even had the most negative effect on morphogenesis. Since morphogenesis of lung histotypic structures is prerequisite for surfactant synthesis and secretion, we hypothesize that a sequential treatment of thyroid hormones to improve morphogenesis followed by the application of glucocorticosteroids might be an option to improve neonatal lung function.

Cripto-1 induces phosphatidylinositol 3'-kinase-dependent phosphorylation of AKT and glycogen synthase kinase 3beta in human cervical carcinoma cells.

Cripto-1 (CR-1), a member of the epidermal growth factor-CFC peptide family, activates the ras/raf/mitogen-activated protein/extracellular signal-regulated kinase/mitogen-activated protein kinase pathway. In the present study, the role of CR-1 in the phosphatidylinositol 3'-kinase (PI3K)/AKT (protein kinase B)/glycogen synthase kinase 3beta (GSK-3beta)-dependent signaling pathway was evaluated in human SiHa cervical carcinoma cells. Our data demonstrate that CR-1 can enhance the tyrosine phosphorylation of the p85 regulatory subunit of PI3K and transiently induce the phosphorylation of AKT in a time- and dose-dependent manner. In addition, CR-1 was found to induce the phosphorylation of GSK-3beta. Phosphorylation of AKT and GSK-3beta by CR-1 can be blocked by LY294002, a specific inhibitor of PI3K, thus leading to apoptosis. Finally, the apoptotic effect of LY294002 can be partially rescued by exogenous CR-1. In summary, our data suggest that human CR-1 may function as a survival factor through a PI3K-dependent signaling pathway involving AKT and GSK-3beta.

Therapy of metastatic breast cancer with humanized antibodies against the HER2 receptor protein.

The HER2 protein, a member of the epidermal growth factor family, is encoded by the protooncogene c-erbB-2. Its overexpression, occurring in approximately one-third of all breast carcinomas, is associated with a poor prognosis. A humanized mouse antibody against HER2 has been developed by genetic engineering. Here an unspecific human IgG was connected to the recognizing mouse IgG fragment. The allergization typical for allogeneic antibodies does not take place in this context. The effectiveness of this antibody has been confirmed by two international prospective phase III trials that tested it alone and combined with chemotherapy. Both modes of application increased the response rates and the time to progression. Side-effects were rare except for a high rate of cardiac dysfunction when the antibody was combined with anthracyclines. The effectiveness and negligible side-effects of the chimeric antibody against HER2 (Herceptin) render it a valuable tool in the treatment of breast cancer.

Failure to demonstrate postpartum functional iron deficiency using quantitative red blood cell analysis.

OBJECTIVE: The aim of this prospective study was to assess erythropoiesis and test for functional iron deficiency in the postpartum period using quantitative red blood cell analysis. STUDY DESIGN: Parameters were determined on admission for delivery and postpartum from 82 obstetric patients at Zurich University Hospital: full blood count, hypochromic and microcytic red cells, reticulocyte count (including subsets), reticulocyte mean corpuscular volume, reticulocyte mean hemoglobin content and reticulocyte mean corpuscular hemoglobin concentration. RESULTS: Microcytic cells increased from 0.9% prepartum to 1.4% on day 42 postpartum; hypochromic cells decreased from 4.3 to 1.9%; reticulocyte mean corpuscular volume decreased from 134 to 125 fl; reticulocyte mean hemoglobin content was unchanged. CONCLUSION: To our knowledge, this is the first medium scale application of quantitative red blood cell analysis to normal pre- and postpartum women. Our data show no evidence of functional iron deficiency or increased erythropoiesis in the postpartum period.

Acute onset of blindness during labor: report of a case of transient cortical blindness in association with HELLP syndrome.

The coincidence of HELLP syndrome and cortical blindness is an uncommon but very dramatic event, for the patient as well as the obstetrician. This report describes the first case of HELLP-syndrome-associated cortical blindness occuring suddenly in the third stage of labour. There were only modest correlates of cortical blindness in cerebral CT, MRI and angiography findings, but no signs of a posterior leucoencephalopathy syndrome. Mother and baby were discharged from hospital to outpatient care in good health on the 12th day.

Effect of epidermal growth factor on enzymes of phospholipid biosynthesis in lung and liver of fetal rat in vivo and in vitro.

Epidermal growth factor (EGF), a mitogenic polypeptide that binds to cell surface receptors, is an important regulator of cell differentiation and fetal lung surfactant synthesis, and may be used as a potential novel therapeutic agent in prematurity. Nevertheless, the distinct role in lung development and its mechanisms of action are not well understood. We investigated in vivo the systemic effect of intrafetally administered EGF (200 ng/g fetal body weight) and maternally administered dexamethasone (DEXA; 0.2 and 2.0mg/kg maternal body weight) on the activity of important enzymes of the phospholipid synthesis in the fetal rat lung and liver: choline kinase (EC 2.7.1.32), cholinephosphate cytidyltransferase (EC 2.7.7.15), choline phosphotransferase (EC 2.7.8.2), lysolecithin acyltransferase (EC 2.3.1.23) and glycerolphosphate phosphatidyltransferase (EC 2.7.8.5). Additionally, in vivo and in vitro effects of DEXA on EGF receptor synthesis, and the effects of EGF on protein content and morphogenesis of the fetal rat lung organoid culture, were evaluated. Whereas DEXA induced the activity of all investigated enzymes of phospholipid synthesis and increased EGF receptor synthesis, EGF has no effects on the enzymes, either in vivo or in vitro. EGF enhanced protein synthesis and morphogenesis in vitro. With respect to our data and the literature, we hypothesize that DEXA and EGF may act on different cellular sides. Whereas glucocorticoids induce surfactant phospholipid synthesis, EGF should be more involved in cell proliferation and morphogenesis.

Photodynamic Therapy of Malignant Ovarian Tumours Cultivated on CAM.

The disappointing results with either surgery alone and/or chemotherapy in the treatment of malignant ovarian tumours have led to an increased interest in additional treatment schedules. Photodynamic therapy (PDT), a modality involving the use of a photosensitising drug and activating light, is being used increasingly as a local treatment for neoplastic lesions. The synthesis and evaluation of new photosensitisers for the treatment of gynaecological lesions and malignancies continues to be an active area of investigation for proper application of the photodynamic process in the gynaecological field. The effect of PDT using methylene blue (free and combined with liposomes) as a photosensitiser for treating human ovarian malignant tumours cultivated on the chorioallantoic membrane was evaluated. Two days after PDT, the treated implanted tumours were markedly decreased in size. Areas of necrosis with black coloration, dryness and eschar formation were observed. Five days after PDT, tumour remission was clearly observed in all the treated tumours. Photodynamic therapy using methylene blue (aqueous and coupled with liposomes) is effective for treating the ovarian malignancies and it will be capable of achieving complete eradication of visible tumours in patients with superficial lesions.

Laser-Induced Thermotherapy (LITT) for Retreatment of Locally Advanced Recurrences of Breast Cancer.

The effect of laser-induced thermotherapy (LITT) as a palliative method for treatment of patients with local recurrence of breast cancer is investigated. This report describes the use of interstitial laser photocoagulation to manage such lesions. The interstitial laser applications were performed in seven women with locally recurrent breast carcinoma on the chest wall after mastectomy. All patients had been heavily pretreated with conventional modes of therapy (radiotherapy, chemotherapy, hormonal therapy, surgical resection). A Nd:YAG laser with a wavelength of 1064 nm was used to heat the lesions. Heat expansion was controlled digitally and monitored by ultrasonography and colour-coded duplex sonography (CCDS). In five women this minimally invasive method enabled the precise coagulation of the subcutaneous tumour without destruction of the skin or ulceration, although these areas had been pretreated by irradiation up to 60 Gy. In two patients with extensive multiple metastases and with skin infiltration, secondary skin ulceration and delayed healing was observed. For palliative reasons, LITT under CCDS guide can aid in local control of chest wall recurrence following mastectomy in selected patients.

Hyperemesis in late pregnancy--should we think of cancer? A case report.

Gastric cancer is unusual during pregnancy. The diagnosis may be delayed because specific symptoms are similar to typical pregnancy associated complaints. Our therapeutic management with palliative chemotherapy and later gastrectomy differs from other known cases, where surgical resection has been the treatment of choice. Surgery appears to have no influence on the prognosis of gastric cancer patients with hepatic metastases.

Stage I primary malignant mixed müllerian tumor of the fallopian tube. Report of a case with five-year survival after minimal surgery without adjuvant treatment.

BACKGROUND: Sarcomas of the fallopian tube are rarities in gynecologic oncology, consisting of < 1% of all genital sarcomas. CASE: A 70-year-old woman with a stage I malignant mixed müllerian tumor (MMMT) (International Federation of Gynecology and Obstetrics classification of fallopian tube carcinomas) did not undergo radical surgery or adjuvant treatment because of the patient's refusal of them. The patient underwent only abdominal hysterectomy with bilateral salpingo-oophorectomy. She was discharged feeling well and without abnormal clinical findings. Sixty months after primary surgery there were no signs of recurrence. CONCLUSION: This case suggests the possibility of a good prognosis in early-stage MMMT, especially if there is no deep infiltration of the fallopian tube muscle layer or lymphatic permeation and if the peritoneal cytology is negative. The important feature of this report is the five year disease-free survival after nonradical surgery for prognostically favorable MMMT.

Is endometrial ablation a safe contraceptive method? Pregnancy following endometrial ablation.

A case of pregnancy following thermal endometrial ablation is presented in this report.

Elevated serum prolactin level with high-dose estrogen contraceptive pills.

BACKGROUND AND OBJECTIVES: There are currently groups of women using high-dose estrogen contraceptive pills, especially in the developing countries. The aim of this study was to determine the correlation between the duration of contraceptive pill intake, the dose of steroid contained in the contraceptive pills and the incidence and degree of serum prolactin level elevation in those women. STUDY DESIGN: This study was conducted in 100 contraceptive pill users. Women were randomly selected for this study with an age range from 19 to 35 years and duration of contraceptive pill intake from 6 to 120 months. Cases were classified into two groups. The first group (50 cases) were taking high-dose estrogen pills (50 micrograms) and the second group (50 cases) were taking low-dose estrogen pills (30 micrograms). RESULTS: The results of the present study showed that there was a significant elevation in serum prolactin level in both groups, with a more significant elevation in the high-dose pill users. CONCLUSIONS: There is a positive relationship between serum prolactin level and the duration of pill intake and their steroid content, and this relationship is not related to the age and parity of the women. The groups of women studied are scheduled for follow-up to determine if there is any future drawback which results as a consequence of the developed hyperprolactinemia. Prolactin determination should be considered for all women prior to pill intake. This determination of serum prolactin level prior to pill use will be useful in the evaluation of the future relationship between the estrogen content of the pills and the later development of hyperprolactinemia.

Prenatal diagnosis of a lethal multiple pterygium syndrome type II. Case report.

Advances in ultrasound technology and sonographer's experience lead to the description of many rare syndromes and malformations through prenatal diagnosis. Diaphragmatic hernia is a rather common malformation but can be an indicator of different syndromes. We report the prenatal diagnosis of lethal multiple pterygium syndrome type II which has been established in the 34th week of pregnancy. The sonographically detectable symptoms consisted of polyhydramnios, hygroma colli, diaphragmatic hernia, scoliosis, short forearms, hypokinesia of the fetus and pterygia over the large joints. Labour was induced in the 34th week of pregnancy; the neonate died shortly after vaginal delivery as a result of the pulmonary hypoplasia. A multidisciplinary approach in prenatal assessment may help to clarify difficult diagnostic problems and may be of direct benefit for the pregnant patient.

Inhibition of 11 beta-hydroxysteroid dehydrogenase activity enhances the antiproliferative effect of glucocorticosteroids on MCF-7 and ZR-75-1 breast cancer cells.

This in vitro study on MCF-7 and ZR-75-1 breast cancer cells showed that the antiproliferative action of glucocorticosteroids (GCS) on breast cancer cells is weakened by a high oxidative activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD; EC 1.1.1.146): both endogenic as well as synthetic GCS (dexamethasone, prednisolone) were metabolised to hormonally inactive 11-dehydro metabolites. This enzymatic shield protected the breast cancer cells from the antiproliferative action of GCS. Continuous exposure of breast cancer cells to GCS resulted in enhanced 11 beta-HSD activity. The intracellular GCS concentration was further reduced by this feedback and thus the antiproliferative effect was additionally weakened. These mechanisms of GCS deactivation could be influenced by inhibiting 11 beta-HSD with the liquorice compound glycyrrhetinic acid (GLY). In MCF-7 and ZR-75-1 cultures the antiproliferative effect of GCS was significantly increased by GLY.