Ultrasound evaluation of the multifetal gestation

With the increasing incidence of multifetal gestations, it is essential for the clinician to appreciate the benefit of ultrasound evaluation in these pregnancies. Multifetal gestation pregnancies are at increased risk for a range of both antepartum and intrapartum complications, such as intrauterine growth restriction, premature delivery, congenital anomalies, cord accidents, malpresentations, placenta previa, and abruptio placentae. First-trimester ultrasonic evaluation, amniotic fluid assessment, monitoring of fetal growth, diagnosing the twin-to-twin transfusion syndrome, and assessment of fetal anomalies will be reviewed. An early and accurate assessment of amnionicity and chorionicity are paramount in these gestations. The impact of chorionicity, in particular, can have profound consequences in the management of multifetal gestations. The determination of chorionicity onultrasonic evaluation in a multifetal gestations. The determination of chorionicity on ultrasonic evaluation in a multifetal pregnancy should be determined in a systematic way between 10-14 weeks' gestation. The amniotic fluid volume should be routinely assessed when performing an ultrasonic evaluation in a multifetal pregnancy. Amniotic fluid changes may serve as the only useful indicator to a potential pathological condition. In addition, evaluation of fetal growth in twins is essential, because these pregnancies are at increased risk for growth restriction and increased perinatal mortality rates compared to singletons. Finally, a careful anatomical evaluation in mulitifetal gestation is important because twin pregnancies have higher rates of anomalies than their singleton counterparts.     

Occupancy of striatal and extrastriatal dopamine D2/D3 receptors by olanzapine and haloperidol.

There have been conflicting reports as to whether olanzapine produces lower occupancy of striatal dopamine D(2)/D(3) receptor than typical antipsychotic drugs and preferential occupancy of extrastriatal dopamine D(2)/D(3) receptors. We performed [(18)F] fallypride PET studies in six schizophrenic subjects treated with olanzapine and six schizophrenic subjects treated with haloperidol to examine the occupancy of striatal and extrastriatal dopamine receptors by these antipsychotic drugs. [(18)F] setoperone PET studies were performed in seven olanzapine-treated subjects to determine 5-HT(2A) receptor occupancy. Occupancy of dopamine D(2)/D(3) receptors by olanzapine was not significantly different from that seen with haloperidol in the putamen, ventral striatum, medial thalamus, amygdala, or temporal cortex, that is, 67.5-78.2% occupancy; olanzapine produced no preferential occupancy of dopamine D(2)/D(3) receptors in the ventral striatum, medial thalamus, amygdala, or temporal cortex. There was, however, significantly lower occupancy of substantia nigra/VTA dopamine D(2)/D(3) receptors in olanzapine-treated compared to haloperidol-treated subjects, that is, 40.2 vs 59.3% (p=0.0014, corrected for multiple comparisons); in olanzapine-treated subjects, the substantia nigra/VTA was the only region with significantly lower dopamine D(2)/D(3) receptor occupancy than the putamen, that is, 40.2 vs 69.2% (p<0.001, corrected for multiple comparison). Occupancy of 5-HT(2A) receptors was 85-93% in the olanzapine- treated subjects. The results of this study demonstrated that olanzapine does not produce preferential occupancy of extrastriatal dopamine D(2)/D(3) receptors but does spare substantia nigra/VTA receptors. Sparing of substantia nigra/VTA dopamine D(2)/D(3) receptor occupancy may contribute to the low incidence of extrapyramidal side effects in olanzapine-treated patients.     

Elevated serum cytokines correlated with altered behavior, serum cortisol rhythm, and dampened 24-hour rest-activity patterns in patients with metastatic colorectal cancer.

PURPOSE: Incapacitating symptom burden in cancer patients contributes to poor quality of life (QOL) and can influence treatment outcomes because of poor tolerance to therapy. In this study, the role of circulating cytokines in the production symptoms in cancer patients is evaluated. EXPERIMENTAL DESIGN: Eighty patients with metastatic colorectal cancer with either normal (group I, n = 40) or dampened (group II, n = 40) 24-hour rest/activity patterns measured by actigraphy were identified. Actigraphy patterns were correlated with QOL indices, serum cortisol obtained at 8:00 a.m. and 4:00 p.m. and with serum levels of transforming growth factor-alpha, tumor necrosis factor-alpha, and interleukin 6 (IL-6) obtained at 8:00 a.m. and analyzed in duplicate by ELISA. Cytokine levels and survival were also correlated. RESULTS: Group II patients had significantly higher pre treatment levels of all three cytokines, displayed significantly poorer emotional and social functioning, had higher fatigue, more appetite loss, and poorer performance status compared with group I patients. Transforming growth factor-alpha (TGF-alpha) and IL-6 were significantly increased in the patients with WHO performance status >1 and in those with appetite loss. Fatigue was significantly associated with elevated TGF-alpha only. IL-6 was increased in those patients with extensive liver involvement and multiple organ replacement, and it was significantly correlated with dampened cortisol rhythm. In a multivariate analysis, IL-6 was correlated with poor treatment outcome. CONCLUSIONS: Significant correlations were found between serum levels of TGF-alpha and IL-6, circadian patterns in wrist activity and serum cortisol and tumor-related symptoms in patients with metastatic colorectal cancer. These data support the hypothesis that some cancer patient's symptoms of fatigue, poor QOL, and treatment outcome are related to tumor or host generated cytokines and could reflect cytokine effects on the circadian timing system. This interplay between cytokine signaling pathways, the hypothalamic-pituitary-adrenal axis, the autonomic nervous system, and efferent pathways of the suprachiasmatic nucleus that control circadian physiology, opens the way to new rational interventions for symptom management in cancer patients.     

RNA interference demonstrates a novel role for integrin-linked kinase as a determinant of pancreatic adenocarcinoma cell gemcitabine chemoresistance.

Integrin-linked kinase (ILK) facilitates signal transduction between extracellular events and important intracellular survival pathways involving protein kinase B/Akt. We examined the role of ILK in determining pancreatic adenocarcinoma cellular chemoresistance to the nucleoside analogue gemcitabine. Cellular ILK expression was quantified by Western blot analysis. We examined the effects of overexpression of active ILK and of ILK knockdown induced by RNA interference on gemcitabine chemoresistance. We also examined the effects of modulating ILK expression on gemcitabine-induced caspase 3-mediated apoptosis, phosphorylation status of Akt (Ser473) and glycogen synthase kinase. Overexpression of ILK increased cellular gemcitabine chemoresistance, whereas ILK knockdown induced chemosensitization via increased caspase 3-mediated apoptosis. ILK knockdown attenuated Akt Ser473 and glycogen synthase kinase phosphorylation, whereas overexpression of constitutively active myristoylated Akt was sufficient to induce significant recovery in gemcitabine chemoresistance in the presence of ILK knockdown. Levels of ILK expression affect gemcitabine chemoresistance in pancreatic adenocarcinoma cells. This novel finding suggests that therapies directed against ILK and its downstream signaling targets may have the potential to enhance the efficacy of gemcitabine-based chemotherapy.     

Results of 58872 and 58921 trials in acute myeloblastic leukemia and relative value of chemotherapy vs allogeneic bone marrow transplantation in first complete remission: the EORTC Children Leukemia Group report.

The first EORTC (European Organization of Research and Treatment of Cancer) acute myeloblastic leukemia (AML) pilot study (58872) was conducted between January 1988 and December 1991. Out of 108 patients, 78% achieved complete remission (CR), and event-free survival (EFS) and survival rates (s.e., %) at 7 years were 40 (5) and 51% (6%), respectively. It indicated that mitoxantrone could be substituted for conventional anthracyclines in the treatment of childhood AML without inducing cardiotoxicity. The aim of the next EORTC 58921 trial was to compare the efficacy and toxicity of idarubicin vs mitoxantrone in initial chemotherapy courses, further therapy consisting of allogeneic bone marrow transplantation (alloBMT) in patients with an HLA-compatible sibling donor or chemotherapy in patients without a donor. Out of 177 patients, recruited between October 1992 and December 2002, 81% reached CR. Overall 7-year EFS and survival rates were 49 (4) and 62% (4%), respectively. Out of 145 patients who received the first intensification, 39 had a sibling donor. In patients with or without a donor, the 7-year disease-free survival (DFS) rate was 63 (8) and 57% (5%) and the 7-year survival rate was 78 (7) and 65% (5%), respectively. Patients with favorable, intermediate and unfavorable cytogenetic features had a 5-year EFS rate of 57, 45 and 45% and a 5-year survival rate of 89, 67 and 53%, respectively.     

Windows 99: a source of suburban pediatric trauma

BACKGROUND: Falls from windows in urban areas cause a significant number of pediatric injuries. Window falls have not been well described in the nonurban setting. We describe the epidemiology of window falls from residential homes among pediatric patients at a suburban Level I trauma center. METHODS: A review of patients admitted from January 1991 through November 1999 to a center serving a rapidly growing suburban area was performed. RESULTS: A total of 2,322 children, ages 0-14 years, were admitted during the study period. Falls comprised 41% of these admissions, and 11% of falls were from windows, greater than twice the national average. More than 39% of children who fell from windows were admitted directly to the intensive care unit. Overall mortality rate was 4%. Ages 0 to 4 years comprised the largest percentage (83%), and all children who died were in this age group. Children < or = 4 years were more likely to have an Abbreviated Injury Score > or = 2 (head injury) than those ages 10 to 14 years (p = 0.032). More than 31% of all children injured in window falls seen at the study institution between 1991 and 1999 were admitted in the last 2 years. CONCLUSION: Pediatric falls from windows in this suburban area appear to be increasing, with an incidence greater than the national average. Children at greatest risk are less than 4 years old. Further research in injury prevention at the national level aimed at suburban areas may be warranted.     

Postvaccinal,Corticosteroid‐resistant Bullous Pemphigoid in Infancy: Treatment with Intravenous Immunoglobulin

Bullous pemphigoid is an autoimmune subepidermal blistering disorder that typically affects elderly adults but can also occur in childhood. We report on a 3‐month‐old boy who developed bullous pemphigoid 1 week after the second routine administration of a hexavalent vaccine. The disease was resistant to standard therapies (including oral and topical corticosteroids) but was relieved by intravenous immunoglobulin treatment. There was no recurrence of bullous pemphigoid after the next vaccination (3 mos after discontinuation of steroids).     

Fractional Factorial Design Study on the Performance of GAC-Enhanced Electrocoagulation Process Involved in Color Removal from Dye Solutions

The aim of this study was to determine the effects of main factors and interactions on the color removal performance from dye solutions using the electrocoagulation process enhanced by adsorption on Granular Activated Carbon (GAC). In this study, a mathematical approach was conducted using a two-level fractional factorial design (FFD) for a given dye solution. Three textile dyes: Acid Blue 74, Basic Red 1, and Reactive Black 5 were used. Experimental factors used and their respective levels were: current density (2.73 or 27.32 A/m²), initial pH of aqueous dye solution (3 or 9), electrocoagulation time (20 or 180 min), GAC dose (0.1 or 0.5 g/L), support electrolyte (2 or 50 mM), initial dye concentration (0.05 or 0.25 g/L) and current type (Direct Current—DC or Alternative Pulsed Current—APC). GAC-enhanced electrocoagulation performance was analyzed statistically in terms of removal efficiency, electrical energy, and electrode material consumptions, using modeling polynomial equations. The statistical significance of GAC dose level on the performance of GAC enhanced electrocoagulation and the experimental conditions that favor the process operation of electrocoagulation in APC regime were determined. The local optimal experimental conditions were established using a multi-objective desirability function method.