Comorbidities in head and neck cancer: agreement between self-report and chart review.

OBJECTIVES: To determine the accuracy of self-reported comorbidities compared with medical record review and the clinical and sociodemographic characteristics associated with accuracy of self-reported comorbidities. STUDY DESIGN: We conducted a prospective study of 458 newly diagnosed head and neck cancer patients using self-administered questionnaire and medical chart review data. Overall and itemwise consistency between self-report and chart review was evaluated. Social, clinical, and demographic characteristics of consistent versus inconsistent responders were analyzed. RESULTS: Seventy-four percent of patients had at least one comorbidity. There was good overall consistency between self-report and chart review (kappa = 0.50). Compared with consistent responders, inconsistent responders were found to be older (P < 0.05), have lower sleep (P < 0.05) and physical activity scores (P < 0.05), be more depressed (P < 0.05), and have more severe comorbidities (P < 0.05). CONCLUSIONS AND SIGNIFICANCE: Self-report may be considered as an alternative to chart review for comorbidity assessment in head and neck cancer patients. Younger patients, those with good general health, fewer depressive symptoms, and mild comorbidities, are more likely to give responses consistent with chart review.     

Characterization of RAFTK, a novel focal adhesion kinase, and its integrin-dependent phosphorylation and activation in megakaryocytes

We have recently isolated a cDNA encoding a novel human intracellular tyrosine kinase, termed RAFTK (for a related adhesion focal tyrosine kinase). The RAFTK cDNA, which encodes a polypeptide of 1,009 amino acids, shares 65% homology to the focal adhesion kinase (FAK), including several consensus motifs. In this report, we describe the biochemical characterization and functional analysis of the RAFTK protein. Coexpression of RAFTK and FAK proteins in megakaryocytic cells and blood platelets was observed. Using a specific antibody to RAFTK and the monoclonal antibody 2A7 to FAK, FAK and RAFTK could be distinguished antigenically. RAFTK had intrinsic tyrosine kinase and autokinase activities. It was phosphorylated on tyrosine in growing cultures of COS cells transfected with the pCDNAIII/flag-RAFTK expression vector containing the RAFTK cDNA ligated with the 8 amino acid flag peptide sequence. Similar to FAK, dephosphorylation of RAFTK was observed when adherent transfected COS cells were detached. Phosphorylation was regained upon replating of these cells on the fibronectincoated dishes. Analysis of tyrosine-phosphorylated RAFTK from adherent transfected COS cells showed that the Src homology 2 (SH2) domains of the Src and Fyn protein kinases as well as the Grb2 adaptor protein were able to specifically associate with RAFTK. Tyrosine phosphorylation of endogenous RAFTK was observed upon fibronectin-induced activation of human megakaryocytic cells. Furthermore, colocalization of RAFTK protein with vinculin, a focal adhesion protein, was observed by confocal microscopy in focal adhesion- like structures in adherent CMK cells and in transfected pCDNAIII/flag- RAFTK COS cells upon fibronectin activation. These data suggest that RAFTK is a novel member of the FAK family, that it localizes to focal adhesion-like structures in CMK megakaryocytic cells, that it participates in integrinmediated signaling pathways in megakaryocytes, and that it is able to associate with the tyrosine kinases Src and Fyn as well as the adaptor protein Grb2 via SH2-phosphotyrosine interactions.     

Decreased brain metabolism in neurologically intact healthy alcoholics.

OBJECTIVE: The extent to which cerebral dysfunction in alcoholics is related to the direct effects of alcohol in the brain rather than to indirect mechanisms and/or alcohol withdrawal remains unclear. The purpose of this study was to evaluate whether healthy alcoholics with no evidence of alcohol-associated complications showed changes in brain glucose metabolism. METHOD: Positron emission tomography and [18F]-fluorodeoxyglucose were used to measure regional brain metabolism. The study group consisted of 22 normal, healthy, right-handed volunteers and 22 neurologically intact, healthy, right-handed alcoholics tested 6 to 32 days after alcohol discontinuation. RESULTS: Alcoholics showed significantly lower whole brain metabolism than normal control subjects. Normalization of regional metabolic values to the whole brain metabolic rate revealed that the left parietal and right frontal cortices were the most affected regions. Although the whole brain metabolic rate was correlated with the amount of time since alcohol discontinuation, the "normalized" decreases in left parietal and right frontal glucose metabolism were not. CONCLUSIONS: These findings support the contribution of the direct effect of alcohol as well as alcohol withdrawal on the changes in regional brain metabolism seen in alcoholics. They also provide evidence of cerebral changes in neurologically intact healthy alcoholics.     

Behavior-decrementing effects of low doses of haloperidol result from disruptions in response force and duration

By using a factorial experimental design, the joint effects of two levels of sucrose reward, two levels of required force, and four levels of haloperidol dose (0. 0.04, 0.08, 0.16mg/kg) were examined for three measures of operant response: peak force, duration, and interresponse time. Even though a 24% sucrose reward led to more rapid acquisition of the operant than an 8% concentration during the drug-free response shaping period, neither the reward nor the required-force manipulations interacted with haloperidol dose during subsequent testing. Haloperidol had significant elevating effects on peak force and duration of response, while lengthening interresponse time. A within-session analysis revealed drug-related slowing of both response duration and interresponse time as the operant session progressed. Finally, dose effects on peak force and duration were apparent from the beginning of the session, but effects on interresponse time reached significance later in the session. Taken together the results downplay the importance of stimulus efficacy, anhedonia and required effort in accounting for haloperidol's behavior-decrementing effects. Instead, the results raise the possibility that the haloperidol-treated rats experienced difficulty in sensorimotor control of the operant response.     

The Morphologic Effects of Dieldrin and Methyl Mercuric Chloride on Pars Recta Segments of Rat Kidney Proximal Tubules

This investigation was undertaken to evaluate the morphologic effects in rat kidney resulting from chronic exposure to low doses of the pesticide dieldrin, methyl mercuric chloride (CH₃HgCl) and the combination of dieldrin plus CH₃HgCl. Histologic and ultrastructural changes were confined to the proximal tubules. Alterations in these tubules were consistent and reproducible for each regimen and did not become more severe with duration of exposure. The straight segment of the proximal tubule (pars recta) was more severely affected by dieldrin and CH₃HgCl than the convoluted portion. Female rats were more markedly affected than males. Pars recta tubule cells of male and female rats exposed to dieldrin showed an increase of smooth endoplasmic reticulum (SER). Male rats displayed a greater increase in SER than females. Pars recta tubule cells of animals given CH₃HgCl also exhibited increased amounts of SER, degenerating mitochondria and cell death. Pars recta tubules of females were dilated and contained within the lumens many spherical, hematoxylin-positive staining, cytoplasmic masses, which were visible by light microscopy. These masses were characterized ultrastructurally by the presence of an SER aggregate in an area of material similar to cell matrix. In addition, cells of the pars recta of female animals contained electron-dense membranous cytosomes not present in control animals. Pars recta cells of males showed an increase in SER, but the dense membranous cytosomes observed in the pars recta cells of female rats were not seen. Rats exposed to dieldrin plus CH₃CgCl showed less morphologic alteration of the pars recta tubules than animals given methyl mercuric chloride; however, increased amounts of SER and more degeneration in tubule cells were observed in these animals when compared to control animals. The findings are discussed in relation to the conversion of CH₃HgCl to inorganic mercury in vivo and the known toxicity of inorganic mercury to the pars recta. Decreased tubular alteration in males and dieldrin-treated animals may be explained by sexual differences in renal enzyme levels or activities and the induction of microsomal enzyme systems by dieldrin.     

Comparison of radioimmunoassay and ELISA methods for detection of antibodies to chromatin components

A solid phase radioimmunoassay has been compared with an enzyme-linked immunosorbent assay (ELISA) for efficacy in measuring anti-chromatin antibodies. The low backgrounds achieved with the radioimmunoassay method produced a high signal-to-noise ratio and enabled detection of the human test antiserum at a dilution of 1:102,400. By contrast, the ELISA could detect the same antiserum only at a dilution of 1:3200 and above. The radioimmunoassay was consistently more sensitive than the ELISA for detection of anti-chromatin antibodies in a number of human and mouse sera and ascites fluid containing a monoclonal antibody. Factors affecting sensitivity in both assays are discussed.     

Mechanical properties of abdominal aortic aneurysm wall

There is a need to understand why and where the abdominal aortic aneurysm may rupture. Our goal therefore is to investigate whether the mechanical properties are different in different regions of the aneurysm. Aorta samples from five freshly excised whole aneurysms, > or = 5 cm in diameter, from five patients, average age 71 +/- 10 years, were subjected to uniaxial testing. We report the wall thickness, yield stress and strain, and parameters that describe nonlinear stress-strain curves for the anterior, lateral and posterior regions of the aneurysm. The posterior region was thicker than the anterior region (2.73 +/- 0.46 mm versus 2.09 +/- 0.51 mm). The stress-strain curves were described by sigma = a epsilon(b), where sigma is true stress and epsilon is engineering strain. In the circumferential direction, the wall stiffness increased from posterior to anterior to lateral. In the longitudinal direction, the lateral and anterior regions showed greater wall stiffness than the posterior region. The wall stiffness was greater in the circumferential than longitudinal direction. The anterior region was the weakest, especially in the longitudinal direction (yield stress sigmaY = 0.38 +/- 0.18 N mm(-2)). For a less complex model the aneurysmal wall could be considered orthotropic with sigma = 12.89epsilon(2.92) and 4.95epsilon(2.84) in the circumferential and longitudinal directions. For the isotropic model, sigma =7.89epsilon(2.88). In conclusion, different regions of the aneurysm have different yield stress, yield strains, and other mechanical properties, and this must be considered in understanding where the rupture might occur.