Plasma glutathione S-transferase P1-1 levels in patients with head and neck squamous cell carcinoma

BACKGROUND: Many tumors contain high amounts of the detoxification enzyme glutathione S-transferase P1-1 (GSTP1-1). Elevated levels of GSTP1-1 have also been detected in serum and plasma from patients with gastrointestinal, lung, or head and neck tumors. The authors of this report evaluated the role of GSTP1-1 as a plasma tumor marker in patients with head and neck squamous cell carcinoma (HNSCC) of the larynx, hypopharynx, or oropharnyx and in patients with benign head and neck lesions (BHNL). METHODS: GSTP1-1 levels were measured in EDTA plasma combined with ethylenediaminetetraacetic acid using a recently developed sensitive and specific sandwich enzyme-linked immunoadsorbent assay. A normal reference level with an upper limit of 21.8 microg GSTP1-1 per liter of plasma was calculated from results obtained with samples from 230 blood donors. RESULTS: Median GSTP1-1 levels in samples from 53 patients with oral/oropharyngeal SCC (10.6 microg/L; range, 3.7-46.1 microg/L), 12 patients with hypopharyngeal SCC (11.9 microg/L; range, 5.2-146.6 microg/L), and 28 patients with laryngeal SCC (14.4 microg/L; range, 6.4-141.5 microg/L) were significantly elevated when compared with plasma GSTP1-1 levels in samples from 45 patients with BHNL (8.1 microg/L; range, 3.3-32.3 microg/L; P < 0.0001, P < 0.01, and P < 0.0001, respectively). However, only 6 of 53 patients (11%) with oral/oropharyngeal SCC, 1 of 12 patients (8%) with hypopharyngeal SCC, and 6 of 28 patients (21%) with laryngeal SCC had plasma GSTP1-1 levels above the upper limit of the normal reference level. Thus, only 13 of 93 patients (14%) with HNSCC had elevated plasma GSTP1-1 levels overall. No significant relation between plasma GSTP1-1 levels and TNM classification of the tumors was observed. CONCLUSIONS: GSTP1-1 is not a suitable plasma tumor marker for HNSCC.     

Local synthesis of C3 within the splenic lymphoid compartment can reconstitute the impaired immune response in C3-deficient mice

Mice bearing a disrupted C3 locus (C3-/-) have an impaired Ab response to T-dependent Ags (bacteriophage phiX 174 and nuclear protein-keyhole limpet hemocyanin) characterized by a reduction in number and size of germinal centers and impaired retention of Ag by follicular dendritic cells. To test the importance of C3 synthesized locally within the lymphoid compartment during an immune response to T-dependent Ag, we reconstituted C3-/- mice with wild-type bone marrow of MHC-identical littermates. Engraftment not only restored local C3 synthesis in the spleen, but also rescued the impaired humoral response. The major source of C3 mRNA was MOMA-2+ macrophages localized within the white pulp areas of the spleen. Interestingly, C3 expression is apparently regulated as C3 mRNA was not detected in splenic sections of nonimmune mice. Furthermore, local C3 synthesis by donor macrophages reversed the impaired Ag trapping by splenic follicular dendritic cells in C3-deficient mice.     

Ethnic conflict and the psychology of liberation in Guatemala, Peru, and Puerto Rico

Ethnic identity and conflict in Guatemala, Peru, and Puerto Rico are complexly embedded within dynamic systems of class- and race-based geopolitics. Whereas overt violence and terror have permeated both Guatemalan and Peruvian societies, overt conflict has undermined Puerto Rican nationhood. Despite similarities among these 3 countries of Hispano-America, there are important particularities that inform psychological theory and practice. This article explores selected contributions of a psychology of liberation informed by indigenous psychologies and reflexive praxis. The challenges these conflicts and their consequences pose to psychologists seeking to work with populations most deeply affected by these social inequalities are analyzed. It concludes with suggestions of how psychology can move toward the development of community-based responses to psychosocial oppression that foster enhanced individual and collective development in a context of social change.     

Health aspects of fish and n-3 polyunsaturated fatty acids from plant and marine origin

An expert workshop reviewed the health effects of n-3 polyunsaturated fatty acids (PUFA), and came to the following conclusions. 1. Consumption of fish may reduce the risk of coronary heart disease (CHD). People at risk for CHD are therefore advised to eat fish once a week. The n-3 PUFA in fish are probably the active agents. People who do not eat fish should consider obtaining 200 mg of very long chain n-3 PUFA daily from other sources. 2. Marine n-3 PUFA somewhat alleviate the symptoms of rheumatoid arthritis. 3. There is incomplete but growing evidence that consumption of the plant n-3 PUFA, alpha-linolenic acid, reduces the risk of CHD. An intake of 2 g/d or 1% of energy of alpha-linolenic acid appears prudent. 4. The ratio of total n-3 over n-6 PUFA (linoleic acid) is not useful for characterising foods or diets because plant and marine n-3 PUFA show different effects, and because a decrease in n-6 PUFA intake does not produce the same effects as an increase in n-3 PUFA intake. Separate recommendations for alpha-linolenic acid, marine n-3 PUFA and linoleic acid are preferred.     

Determinants of prognosis in late chronic-phase chronic myelogenous leukemia

PURPOSE: Since interferon alfa (IFN-A) became an established treatment in chronic myelogenous leukemia (CML), more patients are referred to tertiary centers in late chronic phase (ie, > 12 months after diagnosis). Trials conducted in this phase cannot be evaluated precisely unless the features that determine prognosis in late chronic-phase CML are identified. The purpose of this study is to define the prognostic determinants of late chronic-phase CML. PATIENTS AND METHODS: From 1980 to 1997,257 consecutive CML patients referred in late chronic phase were studied. Their clinical characteristics at the time of referral and their association with survival were investigated. A staging model was designed. RESULTS: The median survival from time of referral was 43 months. Pretreatment characteristics associated with worse outcome included older age, poor performance status, splenomegaly, low albumin level, high percentage of blasts or basophils in peripheral blood (PB) or bone marrow, longer duration of chronic phase, and poor-risk group as defined by the Synthesis model. Prior exposure to IFN-A was not associated with worse outcome. By multivariate analysis, characteristics associated with shorter survival were age of 60 years or older, time from diagnosis of 3 years or greater, performance status of 1 or greater, PB basophils of 7% or greater, spleen 10 cm or greater, PB blasts 3% or greater, and albumin level less than 4 g/dL. A model that included age, duration of chronic phase, performance status, and PB basophils was generated. Patients with no, one, two, or three or greater adverse factors had median survivals of 71, 49, 26, and 19 months, respectively. CONCLUSION: A staging model for late chronic-phase CML can stratify patients in four groups with significantly different outcomes. If confirmed in independent populations, such a model could be considered in the analysis of future trials of treatment strategies in late chronic-phase CML.     

Pharmacokinetics of dolasetron with coadministration of cimetidine or rifampin in healthy subjects

This study examines normative bone mineral density (BMD) data, as measured by peripheral quantitative computed tomography of the ultradistal radius, in 332 Scottish women aged 18-90 years, comparing it to a recently reported normal German population. The normative Scottish data were higher in almost all decades compared with German counterpart, percentage differences being +0.002%-+21.6% for total (Qtot), and -0.06%-+31.9% for trabecular (Qtrab) BMD. Differences in calibration of the Stratec XCT-960 and XCT-900 systems are thought to be largely responsible for these differences. Estimated age-related changes were determined in the Scottish population. A cubic regression model best fitted age-related changes in the whole population, and changes as a function of years postmenopause in the postmenopausal subgroup, for Qtot, subcortical (Qscort), and cortical (Qcort) BMD, whereas a parabolic regression model best fitted corresponding changes in Qtrab BMD. Percentage age-related changes (5 years: 10 years postmenopause) in Qtot (-0. 79%-1.12%/year) and Qscort (-0.72%-1.12%/year) were greater than Qtrab (-0.53%-0.56%/year) in the early postmenopausal years. Maximum age-related changes were found at 20 years postmenopause for Qtot (-1.36%/year), Qscort (-1.39%/year), and Qcort (-1.39%/year). This study has highlighted variation in normative data derived by different Stratec pQCT systems. The estimated age-related changes suggest that early postmenopausal bone loss preferentially affects subcortical rather than trabecular bone at the radius.     

Distribution of distant metastases from newly diagnosed non-small cell lung cancer

BACKGROUND: The purpose of our study was to determine the incidence and locations of M1 disease at presentation in patients with non-small cell lung cancer to help design appropriate preoperative imaging algorithms. METHODS: All patients with non-small cell lung cancer seen between 1991 and 1993 were identified, and records were reviewed. For patients with M1 disease, the sites of distant metastases and the methods of diagnosis were recorded. RESULTS: Of 348 patients identified, 276 (79%) had M0 disease and 72 (21%) had M1 disease. In 40 of 72 patients (56%), M1 disease was detected via chest or abdominal computed tomography (CT). Brain, bone, liver, and adrenal glands were the most common sites of metastatic disease, in decreasing order. Brain metastases often occurred as an isolated finding, although isolated liver metastases were uncommon. CONCLUSIONS: M1 disease was common at presentation, and was often detectable via chest CT. The incremental yield of abdominal CT over chest CT was very small, and therefore abdominal CT is not an effective method of screening for metastases if chest CT has been performed.     

Genetic linkage analysis of multicase families with fibromyalgia syndrome

OBJECTIVE: Based on the reports of familial aggregation of fibromyalgia (FM) syndrome, we investigated its possible genetic linkage to HLA by studying multicase families. METHODS: Forty Caucasian multicase families with a diagnosis of FM (American College of Rheumatology criteria) in 2 or more first degree relatives were investigated. Eighty-five affected and 21 unaffected members of 41 sibships were studied. Depression symptomology was assessed by Zung Self-rating Depression Scale (SDS). HLA typing was performed for A, B, and DRB 1 alleles, and haplotypes were determined with no knowledge of the subject's diagnosis. We investigated genetic linkage to the HLA region by evaluating sibships in multicase families. RESULTS: Sibship analysis showed significant genetic linkage of FM to the HLA region (p = 0.028). Subgroup analysis was also performed for 17 families where the proband was also noted to have depression (with an SDS index value > or =60). We found that the presence of depression did not influence the observed results (p = 0.22). CONCLUSION:. Our study of 40 multicase families confirms existence of a possible gene for FM that is linked with the HLA region. Our results should be regarded as preliminary and their independent confirmation by other studies is warranted.     

A normal initial colonoscopy after age 50 does not predict a polyp-free status for life

OBJECTIVES: The prevalence of colon polyps increases with age in the general population. It is unknown whether a lack of adenomatous polyps determined at one time point after the age of 50 is predictive of a subsequent low risk of polyp development. METHODS: Twenty-nine patients between ages 50 and 70 who had no prior history of polyps and had a normal colonoscopy at least 5 yr previously were recruited for follow-up colonoscopy to evaluate the incidence of neoplastic disease in this presumably low-risk group. RESULTS: The incidence of adenomatous polyps after a mean of 5.74 yr was 41.4% (95% confidence interval: 23.5-61.1%). A total of 20 adenomatous polyps were found in 12 patients. Seven polyps were 5 mm or more in size. CONCLUSIONS: We conclude that in patients with no history of colonic neoplasia who are 50 yr old, or older, the finding of a normal colonoscopy does not predict diminished risk of neoplasia.     

Spatial learning impairment parallels the magnitude of dorsal hippocampal lesions, but is hardly present following ventral lesions

The hippocampus plays an essential role in spatial learning. To investigate whether the whole structure is equally important, we compared the effects of variously sized and localized hippocampal aspiration lesions on spatial learning in a Morris water maze. The volume of all hippocampal lesions was determined. Dorsal hippocampal lesions consistently impaired spatial learning more than equally large ventral lesions. The dorsal lesions had to be larger than 20% of the total hippocampal volume to prolong final escape latencies. The acquisition rate and precision on a probe test without platform were sensitive to even smaller dorsal lesions. The degree of impairment correlated with the lesion volume. In contrast, the lesions of the ventral half of the hippocampus spared both the rate and the precision of learning unless nearly all of the ventral half was removed. There was no significant effect of the location (dorsal or ventral) of damage to the overlying neocortex only. In conclusion, the dorsal half of the hippocampus appears more important for spatial learning than the ventral half. The spatial learning ability seems related to the amount of damaged dorsal hippocampal tissue, with a threshold at about 20% of the total hippocampal volume, under which normal learning can occur.