A comparison of the speech acceptability of good and excellent esophageal and tracheoesophageal speakers

Thirteen esophageal speakers (8 male, 5 female) and 12 tracheoesophageal (t-e) speakers (7 male, 5 female) were placed into eight groups based on gender, voice type, and speaking proficiency (excellent or good). Audio recordings of each speaker reading the Rainbow Passage (Fairbanks, 1960) were made. The resultant samples were judged for acceptability of speech by 25 naive listeners trained in use of a five-point equal-appearing-interval scale. An analysis of variance of the listener data indicated that speaker proficiency but not voice type had a significant effect on judgments of acceptability, indicating that the listeners perceived no difference in the acceptability of esophageal and t-e speech.     

Testosterone Enhances GABA and Taurine but not N-Methyl-D,L-Aspartate Stimulation of Gonadotropin Secretion in the Goldfish: Possible Sex Steroid Feedback Mechanisms

The effects of gonadal steroids on GABA-, taurine (TAU)- and N-methyl-D, L-aspartate (NMA)-induced gonadotropin-II (GTH-II) release were investigated in male and female goldfish in vivo. In sexually regressed goldfish (both sexes mixed), intraperitoneal implantation for 5 to 10 days with solid Silastic pellets containing testosterone (100 μg/g), oestradiol (100 μg/g) or progesterone (100 μg/g) was previously shown to elevate serum sex steroid levels to values comparable to those in sexually mature animals, and to potentiate gonadotropin-releasing hormone-stimulated GTH-II release. In the present study, testosterone but not oestradiol or progesterone enhanced the stimulatory effects of exogenous GABA (100 μg/g) on GTH-II release in vivo. TAU (1 mg/g) stimulated GTH-II release in sexually regressed mixed sex and sexually recrudescent male goldfish, and both testosterone and oestradiol implantation enhanced GTH-II release induced by TAU. The glutamate agonist NMA (25 to 50 μg/g) was also found to stimulate GTH-II release; however it was relatively less effective in elevating serum GTH-II levels than GABA and TAU, and its effects were not modulated by sex steroid treatments. Pretreatment of goldfish with α-methyl-p-tyrosine to deplete brain and pituitary catecholam-ines did not affect NMA action on GTH-II release. Our results indicate that GABA, TAU and NMA are involved in the neuroendocrine regulation of GTH-II release in goldfish, and support the idea that testosterone participates in the positive feedback regulation of pituitary gonadotropin release in a non-mammalian vertebrate by enhancing GABA- and TAU-stimulated GTH release in vivo.     

Expression and activation of 15-lipoxygenase pathway in severe asthma: relationship to eosinophilic phenotype and collagen deposition

BACKGROUND: Although 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE), a product of 15-lipoxygenase (15-LO), may be involved in mild to moderate asthma, little is known about its potential roles in severe asthma. OBJECTIVES: This study was performed to evaluate 15(S)-HETE levels in bronchoalveolar lavage fluid (BALF) from severe asthmatics with and without airway eosinophils and from the control groups. In addition, 15-LO protein expression was examined in endobronchial biopsy, while its expression and activation were evaluated in BAL cells. RESULTS: While 15(S)-HETE levels in BALF were significantly higher in all severe asthmatics than normal subjects, severe asthmatics with airway eosinophils had the highest levels compared with mild, moderate asthmatics and normal subjects. 15(S)-HETE levels were associated with tissue eosinophil numbers, sub-basement membrane thickness and BALF tissue inhibitor of metalloproteinase-1 levels, and were accompanied by increased 15-LO expression in bronchial epithelium. In addition, activation of 15-LO was suggested by the increased proportion of 15-LO in the cytoplasmic membrane of alveolar macrophages from severe asthmatics. CONCLUSION: The data suggest that severe asthmatics with persistent airway eosinophils manifest high levels of 15(S)-HETE in BALF, which may be associated with airway fibrosis. It is likely that 15-LO expression and activation by airway cells explain the increased 15(S)-HETE levels.     

18F]-Dopa positron emission tomography imaging in early-stage, non-parkin juvenile parkinsonism.

There are few reports of positron emission tomography (PET) in juvenile parkinsonism (JP). We report on the results of (18)F-6-fluoro-L-dopa (FD) PET in a 14-year-old patient with JP of 5 years duration associated with atypical features. This is the youngest subject to be investigated to date. There was a severe asymmetric reduction in striatal FD uptake, with a rostrocaudal gradient in the putamen similar to that seen in adult-onset idiopathic parkinsonism. Extensive DNA analysis in this patient did not show mutations in the parkin gene.     

BMI in the Trois‐Rivières study: Child–adult and child–parent relationships

This study evaluated intraindividual child–adult and interindividual child–parent relationships of body mass index (BMI) using data from the Trois‐Rivières semilongitudinal study of growth and development. Intraindividual correlations between age 12 and 35 years were substantial (r² = 36% of variance in women, 30% of variance in men). Interindividual child–parent correlations for mothers and fathers age 36.6 ± 0.4 and 39.5 ± 0.4 years, respectively, were very low to low for daughters age 12 years (r = 0.09, NS and 0.34, P < 0.001 vs. father and mother, respectively) but all very low for sons age 12 years (r = 0.07, NS and 0.16, NS vs. father and mother, respectively). A multiple regression analysis predicted adult BMI from the individual's BMI at 10, 11, 12 years plus the maternal and paternal BMIs as calculated from self‐reported heights and weights. The BMI at age 12 years was a better predictor of adult BMI than the parental BMI in both men and women (P < 0.001) and multivariate analysis revealed that this index at age 12 years was the sole significant predictor of adult BMI for both men and women. The results from our study do not support the hypothesis that parental BMI is a stronger predictor of adult BMI than childhood BMI. However, useful information for the prediction and prevention of adult overweight can be obtained from the BMI at age 12 years. Our results suggest that environmental influences may be the major factor in the present obesity epidemic. Am. J. Hum. Biol. 15:187–191, 2003. © 2003 Wiley‐Liss, Inc.     

Surgeon experience contributes to improved outcomes in pancreatoduodenectomies at high risk for fistula development

BackgroundPancreatoduodenectomies at high risk for clinically relevant pancreatic fistula are uncommon, yet intimidating, situations. In such scenarios, the impact of individual surgeon experience on outcomes is poorly understood.MethodsThe fistula risk score was applied to identify high-risk patients (fistula risk score 7–10) from 7,706 pancreatoduodenectomies performed at 18 international institutions (2003–2020). For each case, surgeon pancreatoduodenectomy career volume and years of practice were linked to intraoperative fistula mitigation strategy adoption and outcomes. Consequently, best operative approaches for clinically relevant pancreatic fistula prevention and best performer profiles were identified through multivariable analysis models.ResultsEight hundred and thirty high-risk pancreatoduodenectomies, performed by 64 surgeons, displayed an overall clinically relevant pancreatic fistula rate of 33.7%. Clinically relevant pancreatic fistula rates decreased with escalating surgeon career pancreatoduodenectomy (–49.7%) and career length (–41.2%; both P < .001), as did transfusion and reoperation rates, postoperative morbidity index, and duration of stay. Great experience (≥400 pancreatoduodenectomies performed or ≥21-year-long career) was a significant predictor of clinically relevant pancreatic fistula prevention (odds ratio 0.52, 95% confidence interval 0.35–0.76) and was more often associated with pancreatojejunostomy reconstruction and prophylactic octreotide omission, which were both independently associated with clinically relevant pancreatic fistula reduction. A risk-adjusted performance analysis also correlated with experience. Moreover, minimizing blood loss (≤400 mL) significantly contributed to clinically relevant pancreatic fistula prevention (odds ratio 0.40, 95% confidence interval 0.22–0.74).ConclusionSurgeon experience is a key contributor to achieve better outcomes after high-risk pancreatoduodenectomy. Surgeons can improve their performance in these challenging situations by employing pancreatojejunostomy reconstruction, omitting prophylactic octreotide, and minimizing blood loss.     

Autographa californica M nucleopolyhedrovirus ProV-CATH is activated during infected cell death

V-CATH, a cathepsin L-like cysteine protease encoded by the baculovirus Autographa californica M nucleopolyhedrovirus, has been shown to play an essential role in host liquefaction. Similar to cellular cathepsin L, V-CATH is synthesized as an inactive proenzyme and is activated by cleavage of the propeptide. Previous studies indicated that removal of the propeptide was rapid, occurring as soon as the protein could be detected by Western blot, 22 h postinfection. We found, however, that these results reflected artifactual processing of the proenzyme. When the protease inhibitor E-64 was used to prevent this aberration, we found that proV-CATH accumulated in infected cells and activation did not begin until the onset of cell death, at approximately 80 h postinfection. Western blot analysis of fractions of live and dead cells isolated by fluorescence-activated cell sorting revealed that mature V-CATH was found only in dead cells. The regulation of activation of proV-CATH, therefore, was quite different from that of cellular cathepsins. Acridine orange staining revealed that lysosome integrity was lost in dead cells, an occurrence that could lead to the activation of proV-CATH by lysosomal proteases.     

Docetaxel: a new active agent in the therapy of metastatic breast cancer

Breast cancer is the most common malignancy in women, accounting for about 18% of female cancers, and over half a million new cases are diagnosed worldwide each year. Its incidence increases with age and is currently rising. Although the increased availability of screening programs has allowed earlier detection and treatment of primary breast cancers, many patients relapse with metastases after apparently successful treatment of their primary tumor and over 15,000 women in the UK and about 50,000 in the USA die from advanced disease each year. The natural course of breast cancer is very variable even after the development of metastases, and depends on a variety of tumor characteristics and prognostic factors. This is reflected in the large number of treatments currently employed. However, despite this wide choice and considerable research over the years, treatment of metastatic breast cancer (MBC) prolongs average survival times only slightly. Current therapy is aimed at achieving a balance between producing maximal tumor shrinkage to produce the most effective possible palliation of symptoms, and minimizing adverse effects. Anticancer chemotherapy is the preferred option in patients who do not respond to hormones, those with hormone-independent tumors, those with aggressive breast cancer subtypes. A variety of anticancer chemotherapy regimens, using both single and combined agents, have been shown to be effective in achieving tumor regression in MBC. Anthracyclines (doxorubicin, epirubicin) are the most active of the established monotherapies, typically producing response rates of 50-60% during initial (first-line) treatment for metastatic disease, but being effective in fewer than 25% of patients requiring second-line therapy. The drawbacks of anthracyclines include dose-limiting cumulative cardiotoxicity and the development of resistant tumor clones after the use of anthracyclines for adjuvant or first-line therapy, especially if subsequent courses are required within a year. The success of these established chemotherapeutic agents depends greatly on the number and location of metastatic sites. Lymph node and soft tissue secondaries tend to respond well, while visceral metastases (especially in the liver) carry a particularly poor prognosis despite treatment. The outlook for patients with metastases involving more than two organ systems is also bleak. Although some patients can live for years with metastatic disease, the average survival time in patients with MBC is 18-24 months, while in those with liver metastases, life expectancy averages only 6 months. High-dose anticancer chemotherapy with granulocyte-colony stimulating factor (G-CSF) or autologous bone marrow transplantation has allowed the dose intensity of anthracyclines to be increased, and has improved the response rate to about 70% in selected patients with MBC. However, this approach has not been proven to improve survival, involves the risk of greater toxicity and drug-related mortality, and patients with reduced clearance of anthracyclines due to hepatic dysfunction from liver metastases may not be suitable candidates. A number of new anticancer agents have also recently been introduced in an attempt to improve on the performance and avoid the tolerability problems associated with anthracyclines. Among these, antitubulin agents (taxoids and vinorelbine) have shown highly promising activity in MBC. This paper reviews the preclinical, phase I and phase II data for one taxoid, docetaxel. Docetaxel (Taxotere) belongs to the taxoid class of cytotoxic agents, the development of which began more than 20 years ago. In 1971, paclitaxel (Taxol) was identified as the active compound of the crude extract of the bark of the Pacific Yew tree Taxus brevifolia. However, at that time the development of paclitaxel was hampered because of the limited source of the drug and difficulties with isolation, extraction and formulation. The second active taxoid, docetaxel, was isolated by Potier et al. in 1986. Docetaxel is prepared from a non-cytotoxic precursor, extracted from the needles of the European Yew tree Taxus baccata, that is condensed with a chemically-synthesized side-chain. As the docetaxel precursor is freely available because of the regenerating capacity of the needles the development of docetaxel has thus been rapid.