Weight loss predicts mortality after recurrent oral cavity and oropharyngeal carcinomas

BACKGROUND: The prognosis of patients with recurrent tumors of the head and neck generally is considered poor. Better prediction of outcomes can help physicians counsel patients about the merits of additional treatment. The TNM system, which was created for patients with primary tumors, may not provide optimal information. Anatomic staging systems traditionally have ignored symptom-based variables, such as weight loss, despite their known prognostic value. The objectives of this study were 1) to measure the prognostic impact of weight loss, 2) to evaluate the prognostic value of the TNM staging system, and 3) to create a practical staging system capable of predicting survival after patients develop recurrent tumors of the oral cavity and oropharynx. METHODS: A retrospective chart review was used to identify an inception cohort of patients seeking treatment for recurrent, persistent, and second primary tumors of the oral cavity and oropharynx at the University of Washington. The primary outcome variable was 1-year survival. RESULTS: The 1-year survival rate for the cohort (n = 97 patients) was 38%, with a median survival of 0.7 years. Multivariate analysis (Cox regression) identified weight loss, previous radiation to the head and neck, and TNM stage of the recurrent tumor as factors that had a substantial impact on mortality. A second multivariate technique called conjunctive consolidation was used to determine the relative quantitative impact of each variable on survival and to develop a clinical staging system. Weight loss and previous radiation had the greatest influence, and the use of just these two variables resulted in a three-tiered staging system with 1-year survival rates of 62% (16 of 26 patients), 44% (18 of 41 patients), and 10% (3 of 30 patients). In contrast, the TNM staging system produced survival rates of 60% (patients with Stage I disease), 67% (patients with Stage II disease), 32% (patients with Stage III disease), and 32% (patients with Stage IV disease). CONCLUSIONS: The authors found substantial variation in survival after patients developed recurrent tumors of the oral cavity and oropharynx. Two readily available clinical variables--weight loss and previous radiation--were combined to create a clinically practical staging scheme with more prognostic power than the TNM staging system. Until molecular markers can reliably used be to predict outcomes, greater attention needs to be given to the utility of simple, inexpensive, and surprisingly powerful clinical variables.     

Three new C-14 oxygenated taxanes from the wood of Taxus yunnanensis

Three new C-14 oxygenated taxane-type diterpenes, hongdoushans A-C (1-3), were isolated from the wood of Taxus yunnanensis together with four known diterpenes and two lignans. The absolute stereochemistry of the 2-methylbutyryloxy group attached at C-14 of the taxane skeleton was determined to be S by GC analysis of the methyl ester of 2-methylbutyric acid obtained after alkaline hydrolysis of 1 and 4 followed by treatment with CH(2)N(2). The complete stereostructure of the known compound 2alpha,5alpha,10beta-triacetoxy-14beta-[(S)-2-methylbutyryloxy]-4(20),11-taxadiene (4) was established for the first time. The isolates obtained were evaluated for their antiproliferative activity toward murine colon 26-L5 carcinoma and human HT-1080 fibrosarcoma cell lines.     

Patient and referring provider satisfaction with teledermatology

BACKGROUND: Teledermatology has become more widely used, but its impact has not been clearly elucidated. We developed a teledermatology program in response to clinical need, based on the store-and-forward approach. OBJECTIVE AND METHODS: Our purpose was to evaluate the satisfaction of patient and referring physician by using telephone interview. RESULTS: Both patients and providers considered this a useful program and would recommend it to a friend or colleague. The patients were split in their overall rating of the program and its ability to treat their skin conditions. Their greatest concern was their lack of direct contact with their dermatologist. Other common concerns were waiting time and follow-up. Privacy concerns were not commonly mentioned. Providers expressed greater satisfaction than their patients. Their greatest concerns involved the inability of the program to handle the demand. CONCLUSION: The program provided a service that was valued by both patients and providers. The most common concern was the impact on the physician-patient relationship.     

Idiopathic CD4+T-cell lymphocytopenia associated with vitiligo

The syndrome of idiopathic CD4+ T lymphocytopenia (ICTL) is defined as the persistent depletion of peripheral blood CD4+ T lymphocytes below 300 cells/mm(3) or less than 20% of the total lymphocytes in the absence of either HIV infection or other known causes of immunodeficiency. To date no known viral origin has been identified. ICTL has a variable clinical course ranging from patients with minimal symptoms to those who have died from opportunistic infections. We report a case of a 32-year-old white man with a long history of vitiligo that is associated with ICTL. He also had incidental psoriasis. The correlation between ICTL and autoimmune vitiligo suggests an aberration in the immune surveillance that leads to an abnormal response of CD4+ T lymphocytes in the host.     

Alleles at the Nicastrin locus modify presenilin 1- deficiency phenotype

Presenilin 1 (PS1), presenilin 2, and nicastrin form high molecular weight complexes that are necessary for the endoproteolysis of several type 1 transmembrane proteins, including amyloid precursor protein (APP) and the Notch receptor, by apparently similar mechanisms. The cleavage of the Notch receptor at the "S3-site" releases a C-terminal cytoplasmic fragment (Notch intracellular domain) that acts as the intracellular transduction molecule for Notch activation. Missense mutations in the presenilins cause familial Alzheimer's disease by augmenting the "gamma-secretase" cleavage of APP and overproducing one of the proteolytic derivatives, the Abeta peptide. Null mutations in PS1 inhibit both gamma-secretase cleavage of APP and S3-site cleavage of the Notch receptor. Mice lacking PS1 function have defective Notch signaling and die perinatally with severe skeletal and brain deformities. We report here that a genetic modifier on mouse distal chromosome 1, coinciding with the locus containing Nicastrin, influences presenilin-mediated Notch S3-site cleavage and the resultant Notch phenotype without affecting presenilin-mediated APP gamma-site cleavage. Two missense substitutions of residues conserved among vertebrates have been identified in nicastrin. These results indicate that Notch S3-site cleavage and APP gamma-site cleavage are distinct presenilin-dependent processes and support a functional interaction between nicastrin and presenilins in vertebrates. The dissociation of Notch S3-site and APP gamma-site cleavage activities will facilitate development of gamma-secretase inhibitors for treatment of Alzheimer's disease.     

Nitrogen assimilation and growth of wheat under elevated carbon dioxide

Simultaneous measurements of CO(2) and O(2) fluxes from wheat (Triticum aestivum) shoots indicated that short-term exposures to elevated CO(2) concentrations diverted photosynthetic reductant from NO(3)(-) or NO(2)(-) reduction to CO(2) fixation. With longer exposures to elevated CO(2), wheat leaves showed a diminished capacity for NO(3)(-) photoassimilation at any CO(2) concentration. Moreover, high bicarbonate levels impeded NO(2)(-) translocation into chloroplasts isolated from wheat or pea leaves. These results support the hypothesis that elevated CO(2) inhibits NO(3)(-) photoassimilation. Accordingly, when wheat plants received NO(3)(-) rather than NH(4)(+) as a nitrogen source, CO(2) enhancement of shoot growth halved and CO(2) inhibition of shoot protein doubled. This result will likely have major implications for the ability of wheat to use NO(3)(-) as a nitrogen source under elevated CO(2).