Phase I/II trial of intravenous Doxil and whole abdomen hyperthermia in patients with refractory ovarian cancer.

OBJECTIVE: A phase I/II study of Doxil combined with whole abdomen hyperthermia was conducted in patients with refractory ovarian cancer. Liposomal doxorubicin combined with hyperthermia has been shown to increase both liposomal delivery and drug extravasation into tumour xenografts resulting in enhanced cytotoxic effects. PATIENTS AND METHODS: Thirty patients with either recurrent or persistent epithelial ovarian cancer were enrolled. All patients had either measurable or assessable disease. Patients received intravenous (IV) Doxil at a dose of 40 mg m-2 as a 1-h infusion followed by whole abdomen hyperthermia. The phase I portion of the study was performed to determine the maximal tolerated dose (MTD) of hyperthermia. Quality of life (QoL) was performed at baseline, prior to each cycle and every 3 months. Plasma pharmacokinetic studies were performed with the first cycle. RESULTS: Ten patients participated in the phase I portion of the study which demonstrated that the MTD of hyperthermia was 60 min after either average vaginal and rectal temperatures of 40 degrees C had been achieved or after 30 min of power application, whichever was shorter. All 30 patients were either paclitaxel and/or platinum resistant initially or developed resistant disease. The median number of prior chemotherapeutic regimens was three (range 2-8) and six patients had been previously treated with Doxil. There were three partial responses for a response rate of 10% (95% CI: [2%, 27%]) and eight patients (27%; 95% CI: [12%, 46%]) had disease stabilization. The median time to progression or death was 3.4 months (95% CI: [2.6, 5.2]) and the median survival was 10.8 months (95% CI: [8.8, 17.4]). Twelve patients (40%) experienced palmar-plantar erythrodysesthesia (PPE), but only four (13%) experienced grade 3-4 PPE toxicity. Doxil systemic exposure was higher in those with grade 3-4 PPE compared to those with no PPE. None of the patients had grade 3-4 thermal toxicity due to hyperthermia. QoL was not decreased in patients responding to therapy. CONCLUSIONS: Therapy with intravenous Doxil and whole abdomen hyperthermia for patients with platinum/paclitaxel resistant ovarian cancer is feasible and does not negatively impact quality of life.     

Detection of pharyngeal perforation: comparison of aqueous and barium-containing contrast agents

OBJECTIVE: We sought to assess the value of aqueous and barium-containing contrast agents in the detection of pharyngeal perforation. SUBJECTS AND METHODS: Visual and objective in vitro comparisons of an iodinated aqueous contrast agent, a 50% weight/volume barium suspension, and a 100% weight/volume barium suspension were performed. Moreover, to exclude pharyngeal perforation after surgery, we prospectively examined 109 patients by pharyngography, using the aqueous contrast agent and the 100% weight/volume barium suspension. All patients with a pharyngeal perforation were followed up clinically to exclude complications due to barium application. RESULTS: As opposed to the 100% weight/volume barium suspension, in vitro comparison between the aqueous contrast agent and the 50% weight/volume barium suspension yielded no substantial differences. Seventeen perforations could be detected with the aqueous contrast agent. Although 10 of 17 perforations could be slightly better visualized with the 100% weight/volume barium suspension, two perforations were missed with this agent. Five perforations were equally well detected with both. CONCLUSION: Because of a higher radiopacity, 100% weight/volume barium suspensions may more sharply delineate perforations. However, in contrast to aqueous contrast media, narrow pharyngeal perforations can be missed. Thus, the use of a 100% weight/volume barium suspension does not improve the detection of pharyngeal perforation.     

Neue Systematik der Epilepsien und aktuelle Therapieempfehlungen

Monatsschrift Kinderheilkunde - Die aktuelle Klassifikation der Epilepsien aus dem Jahr 2017 gleicht stark der Version des Jahres 1989. Die Versuche einer Reklassifikation in den Jahren 2001, 2006...     

Do gender and birth height of infant affect calorie of human milk? An association study between human milk macronutrient and various birth factors

Objective: The purpose of this study is to analyze the macronutrient of human milk (HM) and to find out the various maternal–infantile factors that can affect HM composition.

Methods: 478 HM samples were collected from healthy and exclusively breast-feeding mothers who delivered healthy term neonates within 3 months. Macronutrient of the samples was analyzed and the birth data were collected.

Results: In multivariate logistic regression analysis, various maternal–infantile factors were found to be associated with HM composition changes; higher fat: cesarean section (OR?=?2.47, p?p?=?0.004); higher protein: postpartum age (OR?=?0.89, p?p?=?0.005) and female infant (OR?=?0.56, p?=?0.012); higher calorie: postpartum age (OR?=?0.95, p?=?0.003), female infant (OR?=?0.33, p?=?0.017), and birth height (OR?=?0.74, p?p?=?0.029), birth height (OR?=?0.73, p?=?0.001), and postpartum age (OR?=?0.95, p?=?0.005) were found as independent risk factors for higher HM calorie.

Conclusion: Various maternal–infantile factors were found to affect HM composition. Interestingly, delivery mode, gender of infant, and birth height were associated with changes in HM macronutrient as well as postpartum age.     

Effect of mosapride on Kv4.3 potassium channels expressed in CHO cells

Mosapride and cisapride are gastroprokinetic agents with 5-hydroxytryptamine₄ receptor agonist activity and have been widely used in the treatment of a variety of gastrointestinal disorders. The effects of mosapride and cisapride on cloned Kv4.3 channels stably expressed in Chinese hamster ovary cells were investigated using the whole-cell patch-clamp technique. Mosapride and cisapride inhibited Kv4.3 in a concentration-dependent manner with IC₅₀ values of 15.2 and 9.8 μM, respectively. Mosapride accelerated the rate of inactivation and activation of Kv4.3 in a concentration-dependent manner and thereby decreased the time to peak. The rate constants of association (k ₊₁) and dissociation (k _?1) for mosapride were 9.9 μM^?1 s^?1 and 151.3 s^?1, respectively. The K _D (k _?1/k ₊₁) was 16.2 μM, similar to the IC₅₀ value calculated from the concentration–response curve. Voltage-dependent inhibition by mosapride was observed in the voltage range for channel opening but was not observed over a voltage range in which all Kv4.3 channels were open. Both the steady-state activation and inactivation curves of Kv4.3 were shifted in the hyperpolarizing direction in the presence of mosapride. Mosapride also caused a substantial acceleration in closed-state inactivation of Kv4.3. Mosapride produced use-dependent inhibition, which was consistent with a slow recovery from inactivation of Kv4.3. M1 and norcisapride, the major metabolites of mosapride and cisapride, respectively, had little or no effect on Kv4.3. These results indicate that mosapride inhibits Kv4.3 by both preferential binding to the open state of the channels during depolarization and acceleration of the closed-state inactivation at subthreshold potentials.     

Benign osteoblastoma of the orbit

Benign osteoblastoma is a rare, solitary, vascular, osteoid-producing tumor that is rich in osteoblasts. This is the first report of a case of osteoblastoma of the orbit not contiguous with a sinus cavity.     

The effect of labour and placental separation on the shedding of syncytiotrophoblast microparticles, cell-free DNA and mRNA in normal pregnancy and pre-eclampsia

The clinical features of the maternal syndrome of pre-eclampsia can be explained by generalised maternal endothelial cell dysfunction, which is a part of a more global maternal systemic inflammatory response. There is growing evidence that these effects are associated with the shedding of cellular debris, including syncytiotrophoblast microparticles (STBM), cell-free DNA and mRNA, from the surface of the placenta (syncytiotrophoblast) into the maternal circulation. The increased shedding of this debris seen in pre-eclampsia is believed to be caused by placental ischaemia, reperfusion and oxidative stress. This study was carried out to determine whether uterine contractions during labour and subsequent placental separation lead to an acute increase in the release of placental debris into the maternal circulation. To assess the effects of labour, samples were taken from 10 normal pregnant (NP) and 10 pre-eclamptic (PE) women at varied time points. Similarly to assess the effects of placental delivery, plasma samples were taken from 10 NP and 10 PE women undergoing elective caesarean section. There was a significant increase in the shedding of STBM in pre-eclampsia which was not seen in normal pregnancy and there was a small rise in STBM levels at placental separation in both normal pregnant and pre-eclamptic women undergoing caesarean section, but the differences were not significant. However, levels of placental cell-free corticotrophin releasing hormone mRNA were significantly increased in labour in both normal pregnancy and pre-eclampsia and were still high 24 h after delivery in the pre-eclamptic women. There was no significant increase in fetal or total DNA in labour, but the overall levels of total DNA (maternal and fetal) was increased in labour in pre-eclampsia compared to normal labour. The enhanced shedding of STBM and CRH mRNA in pre-eclampsia labour may have a role in cases of postpartum worsening of pre-eclampsia.     

Down syndrome biochemical markers and screening for preeclampsia at first and second trimester: correlation with the week of onset and the severity

OBJECTIVES: To estimate the combined screening performance of first and early second trimester prenatal serum markers for Down syndrome, in screening for the development of preeclampsia, and analyze the correlation among marker levels, week of onset, and severity of the disease. METHODS: A retrospective cohort study was carried out on 32 women with preeclampsia and 3044 controls. Serum samples from these pregnancies were assayed for pregnancy-associated plasma protein-A (PAPP-A), alpha-fetoprotein (AFP), unconjugated estriol (uE3), human chorionic gonadotrophin (hCG), and inhibin-A. A likelihood ratio and the odds of being affected given a positive result (OAPR) of various combinations of markers were calculated and receiver operating characteristic (ROC) curves analysis was performed. RESULTS: In the pregnancies that subsequently developed preeclampsia, first trimester PAPP-A concentration was significantly lower and concentrations of early second trimester inhibin-A and hCG significantly elevated. Levels of early second trimester uE3 and AFP were not significantly altered. We also found that inhibin-A correlates with both onset of the disease and the severity. CONCLUSION: Down syndrome biochemical markers levels are altered in those patients who subsequently developed preeclampsia and may be a useful screening test for preeclampsia. Inhibin-A is the most predictive marker and correlates with the severity of subsequent preeclampsia and inversely with the week of occurrence of preeclampsia.     

SAFE--the Special Non-invasive Advances in Fetal and Neonatal Evaluation Network: aims and achievements

In this short review, the objectives and work of SAFE--the Special Non-invasive Advances in Fetal and Neonatal Evaluation Network, a European Union Framework VI network of excellence is described. We demonstrate how this network facilitates the implementation of non-invasive prenatal diagnosis (NIPD) for single gene disorders, fetal rhesus typing, aneuploidy and pregnancy complications.