Peripheral Blood Lymphocyte Surface Antigen Expression and Prognosis in Myeloma: Australian Leukaemia Study Group Study

The Australian Leukaemia Study Group myeloma study (MM1) aimed to determine the prognostic significance of clinical and immunophenotypic markers in patients with multiple myeloma. All patients were treated with standard dose melphalan and prednisone. Seventy-four patients were entered and the median survival was 27 months. Serum beta 2-microglobulin (βM) and albumin levels were the only significant clinical factors influencing survival (p = 0.007 and p = 0.008, respectively). Patients with raised levels of CD38+ lymphocytes at presentation had a significantly shorter survival than patients with normal levels (p = 0.01, logrank test, median 19 months vs 33 months). CD38 antigen expression was independent of β2M but patients with raised levels of CD38 had significantly lower levels of albumin than patients with normal levels (p = 0.001) which may explain their poorer survival. Salmon and Durie stage was not associated with antigen expression. No other B-cell antigens (CD10, CD19, CD20, CD21, CD22, CD23, FMC1 or FMC7) or plasma cell antigens tested (PCA-1) were found to be associated with prognosis. Patients who achieved plateau phase had a better prognosis than those who did not (p = 0.04 in a landmark analysis). Patients who achieved plateau phase following an objective response appeared to have a better prognosis than those who were in plateau phase at presentation (p = 0.09 in a landmark analysis). Light chain isotype suppression (LCIS) was not associated with a significant survival advantage and did not correlate with any known prognostic indicator. We conclude that phenotypic analysis of peripheral blood lymphocytes for CD38 antigen at diagnosis may be useful as a prognostic indicator in patients with myeloma.     

Cytokines and soluble interleukin 2 receptors in rheumatoid arthritis.

Cytokines (IL-1 alpha and IL-2) and soluble interleukin 2 receptors (sIL-2r) were evaluated in patients with rheumatoid arthritis (RA) and controls. In RA, serum sIL-2r and IL-1 alpha were increased, and sIL-2r were significantly higher in synovial fluid than in serum. Serum levels of sIL-1r but not IL-1 alpha were increased in patients with acute infections, suggesting additional discriminatory specificity for IL-1 alpha. Both tender and swollen joint scores were higher for patients with RA with serum sIL-2r levels greater than or equal to 700 U/ml. Quantitation of immune mediators may be useful in the clinical assessment of RA in addition to their implication regarding the pathogenesis of the disease.     

Glucocorticoids Decrease Hippocampal and Prefrontal Activation during Declarative Memory Retrieval in Young Men

Glucocorticoids (GCs, cortisol in human) are associated with impairments in declarative memory retrieval. Brain regions hypothesized to mediate these effects are the hippocampus and prefrontal cortex (PFC). Our aim was to use fMRI in localizing the effects of GCs during declarative memory retrieval. Therefore, we tested memory retrieval in 21 young healthy males in a randomized placebo-controlled crossover design. Participants encoded word lists containing neutral and emotional words 1 h prior to ingestion of 20 mg hydrocortisone. Memory retrieval was tested using an old/new recognition paradigm in a rapid event-related design. It was found that hydrocortisone decreased brain activity in both the hippocampus and PFC during successful retrieval of neutral words. These observations are consistent with previous animal and human studies suggesting that glucocorticoids modulate both hippocampal and prefrontal brain regions that are crucially involved in memory processing. Electronic Supplementary Material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Dopamine neurons projecting to the medial prefrontal cortex possess release-modulating autoreceptors

The ability of dopamine (DA) agonists and antagonists to modulate the K+-evoked overflow of radioactivity from superfused slices of prefrontal cortex of the rat, preincubated with [3H]DA in the presence of 1 microM desipramine, was examined. Apomorphine and the putative autoreceptor-selective DA agonist EMD 23 448 inhibited the K+-evoked overflow of radioactivity, while the DA antagonist sulpiride enhanced the evoked overflow in a dose-dependent and stereoselective manner. The latter effect was partially reversed by EMD 23 448. More than 95% of the radioactivity retained by the slices chromatographed with DA, while deaminated metabolites represented the majority of both the basal efflux (84% metabolites, 4-5% DA) and evoked overflow (84% metabolites, 14% DA) of radioactivity. These findings indicate that mesoprefrontal DA neurons possess release-modulating nerve terminal autoreceptors. Previous studies have shown that these neurons lack synthesis-modulating autoreceptors. Thus, autoreceptors on prefrontal DA terminals appear to be coupled to regulation of the release but not the synthesis of DA.     

Quantitative and qualitative changes of serum proteolytic activity in rats with liver damage induced by galactosamine

Serum proteolytic activity was determined in galactosamine-treated rats and in controls. Injection of the hepatotoxin at a dose of 400 mg/kg resulted in a 3.4-fold elevation in the serum proteolytic activity, while AST (aspartate aminotransferase), ALT (alanine aminotransferase) and bilirubin were increased by factors of 3.9, 8.8 and 4.5, respectively. Studies with proteinase inhibitors revealed that the serum proteolytic activity was partially metal-dependent as well as puromycin and antipain sensitive. Differences in susceptibility to a combination of N-ethylmaleimide and antipain indicated presence of different proteolytic systems in the sera of liver damaged and control rats. Separation of serum proteinases by gel filtration showed that the galactosamine-intoxicated rat serum contained activity which did not appear in the control serum. This activity was partially metal dependent, antipain and N-ethylmaleimide sensitive, and was more susceptible to dithiothreitol than the control activity. These findings demonstrate that hepatocellular damage induced by galactosamine caused not only an increase in serum proteinases, but was also associated with the appearance of enzymes not normally released by the liver of untreated animals.Abbreviations AP alkaline phosphatase - TBil total bilirubin - AST aspartate aminotransferase - ALT alanine aminotransferase - GGT gamma-glutamyltranspeptidase - BiAc bile acids - PrAm primary amines - ProAc proteolytic activity     

Case-control study of colon cancer and drinking water trihalomethanes in Wisconsin

A case-control study was conducted to test the hypothesis that chronic ingestion of trihalomethanes (THMs), occurring as chlorination byproducts in drinking water, carries a risk of colon cancer. Lifetime residential and water source histories and information on water-drinking habits, diet, sociodemographics, medical and occupation histories, lifestyle and other factors were obtained by questionnaire from a statewide sample of newly-diagnosed colon cancer cases (N = 347), controls with cancer of other sites (N = 639) and general population controls (N = 611). Since no data on past THM levels exists, it was necessary to devise a scheme to generate THM estimates for all Wisconsin water sources. For this, a statistical model based on quantitative THM measures and routinely-recorded data taken at 81 municipal water facilities was used in conjunction with individual residential histories to estimate lifetime and period-specific THM exposure for each case and control. Logistic regression was used to estimate odds ratios adjusted for age, sex and urban living, for colon cancer and THM exposure. The study results indicate that THM in Wisconsin drinking water does not pose a significant colon cancer risk. Odds ratios for exposure to the middle and highest category of lifetime cumulative THM were 1.05 (95% Cl = 0.66-1.68) and 0.93(95%Cl = 0.55-1.57) respectively, relative to the cancer control group, and 1.10 (95%Cl = 0.68-1.78) and 0.73 (95% Cl = 0.44-1.21) respectively, relative to the general population controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Safer, more expensive iodinated contrast agents: how do we decide?

The advantages of the new, safer, but more expensive iodinated contrast agents are discussed, and opinions on which patient groups should receive the agents are presented.     

Tumor antigen phenotype, biologic staging, and prognosis in head and neck squamous carcinoma.

Prior studies of alterations in tumor expression of normal blood group antigens and A9/alpha 6 beta 4 integrin, an extracellular matrix receptor, have suggested that these immunohistologic markers reflect the biologic aggressiveness of head and neck squamous carcinomas. To confirm these preliminary observations, prospective long-term follow-up of 82 previously untreated head and neck squamous carcinoma patients was performed. All patients were treated with conventional therapy. Median follow-up was 57 months. Tumor immunohistology for ABH blood group and A9/alpha 6 beta 4 integrin expression was performed and correlated with measures of host cellular immunity, disease-free survival, and overall survival. Loss of blood group expression and high A9/alpha 6 beta 4 integrin expression were each directly related to an increased frequency of early tumor recurrence. The combination of both variables was significantly associated with both disease-free (P = .029) and overall survival (P = .05). Increased expression of A9/alpha 6 beta 4 was associated with impaired T-lymphocyte function (P = .005), and loss of blood group expression was associated with decreased peripheral blood levels of CD8+ T-lymphocytes (P = .013). The findings suggest that these phenotypic characteristics of antigen expression in head and neck squamous carcinomas are important markers of biologically aggressive cancers and impaired host immune response. The clinical use of these biologic staging parameters in the initial assessment of patients should allow selection of more aggressive primary treatment strategies for individual patients.