Bipolar disorder: dominant or recessive on chromosome 5?

Rizatriptan (MK-462) is a potent 5HTID receptor agonist. This multicenter, double-blind, placebo-controlled, outpatient study investigated the clinical efficacy, safety, and tolerability of rizatriptan (2.5, 5, and 10 mg) as a function of dose for acute migraine. Patients with moderate or severe migraine (n = 417) were treated with placebo (n = 67), rizatriptan 2.5 mg (n = 75), 5 mg (n = 130), or rizatriptan 10 mg (n = 145). Headache severity, functional disability, and migraine symptoms were measured immediately before dosing (0) and at 0.5, 1, 1.5, 2, 3, and 4 h post-dose. Patients were permitted to take a second dose of test drug at 2 h if their headache pain was moderate or severe (i.e., placebo initially-->rizatriptan 10 mg as optional second dose; rizatriptan 2.5 mg, 5 mg, or 10 mg initially-->placebo as optional second dose). An upward dose-response relationship was observed among placebo, rizatriptan 2.5 mg, 5 mg, and 10 mg in the primary efficacy measure of proportion of patients reporting pain relief, i.e., a change in headache severity to "no pain or mild pain" at 2 h post-dose. The relationship was evident even at the first recorded timepoint, 30 min, and was statistically significant at 1.5 h and beyond. At the primary timepoint of 2 h after the initial dose, the proportion of patients reporting pain relief was 47.6% for rizatriptan 10 mg; 45.4% for rizatriptan 5 mg; 21.3% for rizatriptan 2.5 mg; and 17.9% for placebo. Seventy percent of patients on rizatriptan 10 mg reported pain relief at 4 h. Patients who took rizatriptan 5 mg and 10 mg were significantly less functionally disabled than those who took placebo at 1.5 and 2 h post-dose. Rizatriptan 10 mg was consistently more effective than 5 mg, although the differences were not statistically significant. The most frequent clinical adverse events were dizziness, somnolence, and asthenia/fatigue. No patients were discontinued for any adverse experiences and there were no serious adverse experiences.     

Cellular uptake properties of a 2''-amino/2''-O-methyl-modified chimeric hammerhead ribozyme targeted to the epidermal growth factor receptor mRNA

PURPOSE: Rhabdomyosarcomas (RMS) are heterogeneous in their clinical presentation, histology, and cytogenetics. The growth of some RMS cells has been found to be regulated by the tyrosine kinase insulin-like growth factor (IGF) type I receptor. However, RMS cells exhibit variable sensitivity to inhibitors of tyrosine kinases and IGF receptors. Collectively, these heterogeneous features suggest that differences exist in the growth regulatory pathways of RMS. The objective of this study is to identify active tyrosine kinase signal transduction pathways in embryonal and alveolar RMS cells. METHODS: RMS tumor samples and cell lines representing both embryonal and alveolar histologic subtypes have been analyzed by immunoprecipitation and immunoblotting techniques to characterize phosphotyrosyl protein patterns and to identify tyrosine phosphorylated proteins. RESULTS: RMS cells can be characterized based on the patterns of phosphotyrosyl proteins, including the phosphorylation status of the catenin-like protein Cas1 and the signal adapter protein SHC, and the activation of IGF type I receptor signaling cascades including the formation of SHC-GRB2 signal protein complexes and MAP kinase activation. CONCLUSIONS: Rhabdomyosarcomas, especially the embryonal histologic subtype, are heterogeneous at the level of tyrosine kinase signal transduction. It will be important to characterize the growth regulatory pathways active in individual RMS tumors before targeting molecular therapies to this malignancy.     

Measurements of H2O2 and HCHO by Tunable Diode Laser Absorption Spectroscopy During the 1986 Carbonaceous Species Methods Comparison Study in Glendora,California

An improved, high sensitivity, tunable diode laser spectrometer system designed for tropospheric air measurements (TAMS-150) was employed during the 1986 Carbonaceous Species Methods Comparison Study at Glendora, CA. The TAMS-150 made simultaneous measurements of H₂O₂ and HCHO with a time response of 3 minutes per data point. The minimum detection limits were respectively 0.1 ppbv and 0.15 ppbv for HCHO and H₂O₂ and the estimated accuracies were ± 20% for both species. During the first 5 days of the study H₂O₂ showed little diurnal variation ranging between 0.25 and 0.5 ppbv with maximum values occurring at 15:30 PDT. During the final 4 days H₂O₂ showed stronger diurnal behavior with mixing ratios ranging from below the detection limits during some nighttime periods to as high as 1.8 ppbv during midday maxima which occurred about 15:30 PDT. HCHO showed strong diurnal behavior throughout the study with rapid changes in concentration in the early morning and evening. Mixing ratios were typically in the range 5–20 ppbv with maxima at about 10:00 and 14:00 PDT.     

Capitating mental health services

Many employers are contracting mental or behavioral health services separately from other types of health care. Capitation rates are paid for a defined set of benefits. Mental health services are capitated in two ways; both approaches are discussed.     

Effects of a peer-led senior health education program

Serotonin (5-hydroxytryptamine; 5-HT) elicits external carotid vasoconstriction in vagosympathectomized dogs via 5-HT1B/1D receptors and a mechanism unrelated to the 5-HT1, 5-HT2, 5-HT3 and 5-HT4 types. In order to further explore the nature of this novel mechanism, the canine external carotid effects of 2-(2-aminoethyl)-quinoline (D-1997), a novel 5-HT1 receptor agonist, were analyzed and compared with those of 5-HT and sumatriptan. Intracarotid (i.c.) infusions of 5-HT, D-1997 and sumatriptan to vagosympathectomized dogs dose-dependently decreased external carotid conductance, the rank order of agonist potency being 5-HT > sumatriptan > D-1997. The effects to D-1997 were resistant to intravenous (i.v.) pretreatment with 5-HT2 and 5-HT3/5-HT4 receptor antagonists. Remarkably, the effects induced by lower (10-100 microg/min), but not higher (300-1000 microg/min), doses of D-1997 were blocked by high doses of methiothepin (1 and 3 mg/kg, i.v.), as previously shown with 5-HT. In addition, GR-127935 (1-10 microg/kg, i.v.), partially and dose-dependently antagonized D-1997-induced responses. However, the effects of D-1997 remained unaltered after blockade of alpha- and beta-adrenoceptors, muscarinic, nicotinic, histamine and dopamine receptors, or inhibition of 5-HT-uptake or cyclo-oxygenase, depletion of biogenic amines or blockade of Ca2+ channels. These results may support our previous contention that lower doses of 5-HT elicit external carotid vasoconstriction in vagosympathectomized dogs by activation of 5-HT1B/1D receptors, whilst higher doses of 5-HT stimulate a novel vasoconstrictor mechanism.     

Equilibrium and kinetic parameters of the sequence-specific interaction of Escherichia coli RNA polymerase with nontemplate strand oligodeoxyribonucleotides

The specific recognition by Escherichia coli RNA polymerase of single-stranded oligodeoxyribonucleotides (oligos) with the sequence of the -10 promoter region on the nontemplate strand has been studied. Binding was monitored by observing the increase in fluorescence of 2-aminopurine residues incorporated in the oligos. The effects of salt on the rates of formation and dissociation of RNA polymerase.oligo complexes are relatively small, from which we conclude that electrostatic interactions contribute minimally to the favorable binding free energy. From the convex temperature dependence of ln Ka (Ka is the equilibrium association constant), we infer that a large apparent negative heat capacity, of 1-2 kcal M-1 K-1, accompanies complex formation, which is interpreted as due to a conformational change in RNA polymerase. Contrary to expectation, the forward rate constant for binding of oligos is more than 10-fold smaller than that for open complex formation at strong promoters. This suggests that in comparison to an oligo, promoter DNA may be better able to accelerate this required conformational change in the RNA polymerase. Oligo binding was shown to compete with the interaction between RNA polymerase and promoters, indicating that the two bind to overlapping sites on the RNA polymerase     

Automated three-dimensional US frame positioning computed from elevational speckle decorrelation

For ultrasonographic B-scan images collected by means of a handheld transducer moving in the elevational direction, frame spacings are computed with a speckle-decorrelation algorithm, without additional positioning hardware. Fully developed speckle volumes are automatically segmented and spacing computed from the decorrelation curves. Position accuracy is within 10% for phantoms and 15% for breast studies. The algorithm provides image-based registration, which allows accurate three-dimensional volume rendering.     

Predicting the development of late-life late-onset drinking problems: a 7-year prospective study

There has been little empirical study of risk factors for the development of late-life late-onset drinking problems. In the current prospective study, we compare two groups of older adults who, at a baseline assessment, were nonproblem drinkers: individuals who developed drinking problems over the course of the next 7 years (n = 77) and those who did not (n = 197). Late-onset problem drinkers reported mild to moderate drinking problems and spontaneous remission rates were high. Compared with stable nonproblem drinkers, late-onset problem drinkers at baseline were more likely to report incipient problems, heavier alcohol consumption, greater friend approval of drinking, more reliance on avoidance coping strategies, were more likely to smoke, and were less likely to have acute medical conditions that could potentially be complicated by alcohol consumption. Contrary to expectation, life stressors did not predict drinking problem onset. However, compared with stable nonproblem drinkers, late-onset problem drinkers were more likely to have a history of responding to stressors and negative affect with increased alcohol consumption.     

Prognostic significance of colony-stimulating factor receptor expression in ipsilateral breast cancer recurrence

The macrophage colony-stimulating factor receptor (CSF-1R), the product of the c-fms proto-oncogene, regulates normal proliferation and differentiation of macrophages and trophoblasts. Recent research found abnormal expression of CSF-1R in human carcinomas of the breast, endometrium, and ovary. Furthermore, activation of CSF-1R by its ligand has been shown to regulate invasiveness and anchorage-independent growth in breast carcinoma cells. To study the significance of CSF-1R expression in breast cancer, we designed a case-controlled immunohistochemical study. We chose 80 patients from a database of 1200 early stage I or II breast cancer patients treated with conservative surgery and radiation therapy. Expression of CSF-1R in the tumors of 40 patients who experienced an ipsilateral breast tumor recurrence (IBTR) as a primary site of relapse were compared with 40 patients who had not experienced an IBTR. The index and control patients were matched by age, clinical stage, nodal status, and follow-up. Paraffin-embedded sections were immunostained with antibodies directed toward CSF-1R. For the CSF-1R antibody, a total of 28 index cases (70%) demonstrated strong staining, whereas only 16 control cases (40%) demonstrated high immunoreactivity (P = 0.007). The CSF-1R antibody showed a positive correlation for local relapse, but no correlation was found between CSF-1R expression and distant metastasis. In summary, our findings provide evidence for the poor prognostic role of CSF-1R in IBTR.