Absolute pitch and pupillary response: effects of timbre and key color

The pitch identification performance of absolute pitch possessors has previously been shown to depend on pitch range, key color, and timbre of presented tones. In the present study, the dependence of pitch identification performance on key color and timbre of musical tones was examined by analyzing hit rates, reaction times, and pupillary responses of absolute pitch possessors (n = 9) and nonpossessors (n = 12) during a pitch identification task. Results revealed a significant dependence of pitch identification hit rate but not reaction time on timbre and key color in both groups. Among absolute pitch possessors, peak dilation of the pupil was significantly dependent on key color whereas the effect of timbre was marginally significant. Peak dilation of the pupil differed significantly between absolute pitch possessors and nonpossessors. The observed effects point to the importance of learning factors in the acquisition of absolute pitch.     

Changes in Weight Associated With Telotristat Ethyl in the Treatment of Carcinoid Syndrome

Purpose

In the placebo-controlled Phase III TELESTAR (Telotristat Etiprate for Somatostatin Analogue Not Adequately Controlled Carcinoid Syndrome) trial, the oral tryptophan hydroxylase inhibitor telotristat ethyl significantly reduced bowel movement (BM) frequency during a 12-week, double-blind treatment period in 135 patients with metastatic neuroendocrine tumors with carcinoid syndrome and ≥4 BMs per day. Patients (mean [SD] age, 63.5 [8.9] years; mean [SD] body mass index, 24.9 [4.9] kg/m²) received placebo, telotristat ethyl 250 mg, or telotristat ethyl 500 mg 3 times per day (TID) in addition to somatostatin analogue therapy. Weight loss is associated with uncontrolled carcinoid syndrome and may be associated with reduced survival.

Neuroendocrine tumours: clinical presentation and management of localized disease

Neuroendocrine tumours often present a diagnostic and therapeutic challenge. They can arise almost anywhere in the body, and are therefore associated with a broad range of local symptoms. The systemic manifestations of neuroendocrine tumours are also diverse, and are related to the secretion of numerous hormones and biogenic amines. In recent years, improved diagnostic techniques, increased recognition of neuroendocrine tumour subtypes, and new therapeutic modalities have enhanced clinicians' ability to detect and appropriately treat these malignancies.     

Allelic loss of 10q23, the PTEN tumour suppressor gene locus, in Barrett's oesophagus-associated adenocarcinoma

PTEN is a putative tumour suppressor gene located on chromosome band 10q23. Mutations in PTEN have been identified in numerous human malignancies, including cancers of the brain, endometrium, ovary, and prostate. In this study, we screened 80 Barrett's oesophagus-associated adenocarcinomas (BOAd) for loss of heterozygosity (LOH) at 10q23, using the microsatellite markers D10S541, D10S219, and D10S551. Tumours demonstrating LOH were then screened for the presence or absence of PTEN mutations. LOH at one or more loci was identified in 17/80 (21%) cases. In none of these cases did we detect mutations in PTEN. The presence of LOH did not correlate with patient age, tumour stage, degree of differentiation, presence of perineural or vascular invasion, or overall survival. We conclude that LOH at chromosome 10q23 is uncommon in BOAd, is not associated with mutations in the PTEN tumour suppressor gene, and does not correlate with the clinical or pathologic features of these tumours. It is possible that PTEN is inactivated through other mechanisms in BOAd.     

DNA degradation test predicts success in whole-genome amplification from diverse clinical samples

The need to apply modern technologies to analyze DNA from diverse clinical samples often stumbles on suboptimal sample quality. We developed a simple approach to assess DNA fragmentation in minute clinical samples of widely different origin and the likelihood of success of degradation-tolerant whole genome amplification (restriction and circularization-aided rolling circle amplification, RCA-RCA) and subsequent polymerase chain reaction (PCR). A multiplex PCR amplification of four glyceraldehyde-3-phosphate dehydrogenase amplicons of varying sizes was performed using genomic DNA from clinical samples, followed by size discrimination on agarose gel or fluorescent denaturing high-performance liquid chromatography (dHPLC). RCA-RCA followed by real-time PCR was also performed, for correlation. Even minimal quantities of longer PCR fragments ( approximately 300 to 400 bp), visible via high-sensitivity fluorescent dHPLC or agarose gel, were essential for the success of RCA-RCA and subsequent PCR-based assays. dHPLC gave a more accurate correlation between DNA fragmentation and sample quality than agarose gel electrophoresis. Multiplex-PCR-dHPLC predicted correctly the likelihood of assay success in formalin-fixed, paraffin-embedded samples fixed under controlled conditions and of different ages, in laser capture microdissection samples, in tissue print micropeels, and plasma-circulating DNA. Estimates of the percent information retained relative to snap-frozen DNA are derived for real-time PCR analysis. The assay is rapid and convenient and can be used widely to characterize DNA from any clinical sample of unknown quality.     

Phase I and pharmacokinetic study of S-1 administered for 14 days in a 21-day cycle in patients with advanced upper gastrointestinal cancer

Purpose S-1 is a novel oral fluoropyrimidine that combines tegafur with CDHP and oxonic acid. To decrease the incidence of late onset, severe diarrhea observed in a previous study, a phase I study was conducted to determine the maximum tolerated dose (MTD) of S-1 utilizing a 14-day schedule, repeated every 21 days, in patients with chemotherapy–refractory upper gastrointestinal malignancies. Methods S-1 was administered orally, twice-daily, at an initial dose level of 30 mg/m²/dose; doses were escalated by 5 mg/m² at each level. A minimum of three patients were enrolled at each dose level. S-1 toxicity, antitumor activity, and pharmacokinetics were assessed. The MTD was based on the dose limiting toxicity (DLT) during the first treatment cycle. Results At 30 mg/m² no DLT was observed in the first three evaluable patients. Two of the first three patients at the 35 mg/m² dose level developed DLTs (grade 3 rash and dehydration). An additional nine patients were subsequently treated at 30 mg/m² without DLT and this dose was established as the MTD. Common toxicities at 30 mg/m² included diarrhea, nausea, skin rash, anorexia, and fatigue. No grade 4 toxicities were observed. One partial response was seen in a patient with gemcitabine-refractory pancreatic adenocarcinoma and ten patients with pancreatic, gastric, or gallbladder carcinomas achieved stable disease as their best response to therapy. The AUC_(0–8) of 5-FU at the 30 and 35 mg/m² dose levels were 875 ± 212 and 894 ± 151 h ng/ml, respectively. Conclusions In a 14-day dosing schedule, the MTD of S-1 was 30 mg/m² and preliminary evidence of antitumor activity was seen in a North American population with refractory upper gastrointestinal malignancies. Supported in part by a grant from Taiho Pharma USA Inc., Princeton, NJ, USA.