Mutagenicity of diisopropylamine dichloroacetate, the "active constituent" of vitamin B15 (pangamic acid)

Diisopropylamine dichloroacetate, the active component of many formulations of pangamic acid (trade-named "vitamin B15"), and diisopropylamine, a component of diisopropylamine dichloroacetate, both demonstrate mutagenicity in the Ames Salmonella/mammalian microsome mutagenicity test. Ninety percent of such agents prove carcinogenic, and this long-term possibility must be considered in any proposed use of pangamic acid containing diisopropylamine or diisopropylamine dichloroacetate.     

Comparison of pesticide and particulate recoveries with the vacuum and dislodgeable surface pesticide residue techniques

The dislodgeable and vacuum surface residue techniques were compared for the quantity of pesticide residue and quantity and quality of particulate matter removed from Valencia orange leaves. Data trends for dislodgeable and vacuum parathion and paraoxon residues were correlated at r0.95 for both emulsifiable concentrate and wettable powder formulations.The amount of pesticide residue and particulate matter obtained was dislodgeable > glass fiber filter > 5.0 filter > 0.8 filter. The flow rate of the filter was correlated with the amount of residue removed.The quality of particulate matter as judged by size analyses was equal The dislodgeable technique removed about five times more particulate material and about eleven times more pesticide residue compared to the vacuum technique.Florida Agricultural Experiment Stations Journal Series No. 745.     

Kahnbeinfrakturen – Diagnostik, Klassifikation und Therapie

Herbert's classification of scaphoid fractures provides the underlying rationale for treatment according to the fracture type. A CT bone scan in the long axis of the scaphoid is the best means of differentiating between stable and unstable fractures. This is difficult from conventional X-rays due to the particular three-dimensional anatomy of the scaphoid. To avoid long-term plaster immobilization and to diminish the risk of a nonunion, unstable fractures of type B should be fixed operatively. With headless screws such as the Herbert screw, which are now available in a cannulated shape, the majority of scaphoid fractures of type B1 and B2 can be stabilized using minimally invasive procedures. Severely displaced fractures require the classical open palmar approach. Proximal pole fractures (B3) are best managed from the dorsal approach, using the Mini-Herbert screw. Stable fractures of type A2 can be treated conservatively in a below-elbow cast or, alternatively, stabilized percutaneously, which allows early mobilization.     

Children of migratory agricultural workers: the ecological context of acute care for a mobile population of immigrant children

Migratory and seasonal agricultural workers fill the labor needs of United States farmers. Although migrant workers are a culturally and ethnically diverse population, presently, they are predominantly immigrants of Hispanic ethnicity. Migrant farm workers are increasingly young, financially impoverished, male, undocumented immigrants from Mexico. Families with children constitute 45% of this population. The ecological context of migrant children’s lives is characterized by poverty, social isolation, heightened inter- and intra-national mobility, limited protections from occupational safety and health legislation, and health access barriers. Moreover, the linkage of citizenship and immigration status to the receipt of public insurance and selected social services benefits has the potential to increase access barriers for migrant workers and their families. Despite these obvious vulnerabilities, few health services research studies address this population. Most of what is known relates to adults, with very little known about migrant children’s health services utilization patterns or health morbidities. In the emergency department setting, the differential approach required to care for children, as compared to adults, must be modified further in order to address the unique needs of this vulnerable population. The effective delivery of acute care to the children of migratory agricultural workers requires awareness of and attention to their unique health access barriers, issues of continuity and compliance with care, and their unique health and injury risks.     

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.     

Induction of p53 up-regulated modulator of apoptosis messenger RNA by chemotherapeutic treatment of locally advanced breast cancer.

PURPOSE: In biopsies of patients with locally advanced breast cancer, we investigated the in vivo changes of the gene expression pattern induced by chemotherapy to find genes that are potentially responsible for the efficacy of the drug. EXPERIMENTAL DESIGN: Early cellular responses to chemotherapy-induced damage, both in vivo and in vitro, were investigated by analyzing chemotherapy-induced changes in gene expression profiles. Core biopsies were taken from nine patients with locally advanced breast cancer, before and at 6 hours after initiation of doxorubicin-based chemotherapy. Both samples were cohybridized on the same microarray containing 18,000 cDNA spots. RESULTS: The analysis revealed marked differences in gene expression profile between treated and untreated samples. The gene which was most frequently found to be differentially expressed was p53 up-regulated modulator of apoptosis (PUMA). This gene was up-regulated in eight of nine patients with an average factor of 1.80 (range, 1.36-2.73). In vitro MCF-7 breast cancer cells exposed to clinically achievable doxorubicin concentrations for 6 hours revealed marked induction of PUMA mRNA, as well. CONCLUSIONS: This is the first report describing PUMA mRNA to be up-regulated as a response to chemotherapy in patients. Because PUMA is a known member of the family of BH3-only proapoptotic proteins, this finding suggests PUMA's potential importance for the response to anticancer drugs.     

The T393C polymorphism of the G alpha s gene (GNAS1) is a novel prognostic marker in bladder cancer.

The G protein G(alpha)s pathway is linked to proapoptotic signaling in cancer cell lines. To assess the role of the GNAS1 locus encoding G(alpha)s as a genetic factor for disease progression of transitional cell carcinoma (TCC) of the bladder, we genotyped the synonymous T393C polymorphism in 254 patients with TCC (minor allele frequency: 0.43) to examine a potential association between genotypes and disease progression. Using Kaplan-Meier estimates to calculate 5-year probabilities of follow-up, we could show that progression-free survival, metastasis-free survival, and cancer-specific survival was significantly increased in TT genotypes (56%, 84%, 82%) compared with CC genotypes (35%, 53%, 58%). In multivariate Cox proportional hazard analysis, the T393C polymorphism was an independent prognostic factor for clinical outcome. Homozygous CC patients were at highest risk for progression [odds ratio (OR), 1.94; P = 0.020], metastasis (OR, 3.49; P = 0.005), and tumor-related death (OR, 2.49; P = 0.031) compared with TT genotypes. Heterozygous patients had an intermediate risk compatible with a gene-dose effect. Real-time PCR analysis of urothelial tumor tissue as well as adipose and heart tissue revealed that G(alpha)s mRNA expression was highest in TT genotypes, indicating a proapoptotic effect in these genotypes. In conclusion, the GNAS1 T393C status associated with differential G(alpha)s mRNA expression is a novel independent prognostic marker for clinical outcome supporting a functional role of G(alpha)s in bladder cancer progression.