Comparison of C-erbB2 (HER-2/Neu) immunohistochemistry results on invasive breast carcinomas. Experience of 2 Pathology departments in Turkey and Greece

OBJECTIVE: To compare c-erbB2 (HER-2/Neu) immunohistochemical staining results obtained in 2 pathology departments and evaluate the reproducibility of staining and assessments. STUDY DESIGN: Ninety primary invasive ductal carcinoma cases constituted the material of this study. For concordant assessment, serial sections from the same tissue blocks were prepared in both Turkey and Greece and were sent to each other. Evaluation of c-erbB2 (HER-2/Neu) staining was done independently in 2 departments by experienced pathologists. Stained slides were evaluated semiquantitatively in Turkey and both semiquantitatively and automatically in Greece. RESULTS: There was complete agreement on staining density in 58 (64.4%) cases in both centers. In 15 cases there were major discordances in staining degrees, and in 17 cases there was a major discordance. Hypothetical treatment decisions based on these results showed that 82% of patients would have been handled the same way. CONCLUSION: Comparison of immunostaining patterns performed at 2 centers provided valuable data that may be used in the development of quality assurance policies. The present study showed the usefulness of multicenter comparative studies in initiating the development of guidelines.     

Serum levels of tumor necrosis factor alpha correlate with response to neoadjuvant chemotherapy in locally advanced breast cancer

It has been shown that serum levels of tumor necrosis factor alpha (TNF-alpha) are increased in breast cancer patients. There are few data available on the reduction of serum levels of this cytokine following chemotherapy. The aim of this study was to determine the effect of neoadjuvant chemotherapy on serum concentrations of TNF-alpha and the relation to response rates in locally advanced breast cancer. Twenty consecutive patients with non-inflammatory stage III-B breast cancer achieving a partial or complete clinical response to three courses of neoadjuvant chemotherapy followed by modified radical mastectomy were prospectively included in the study and evaluated. Sera were collected before the start and after the termination of chemotherapy. Serum concentrations of TNF-alpha were measured by an ELISA method. The pathological response rates were also evaluated and recorded. The control group consisted of 12 healthy age-matched women. The mean pre-treatment TNF-alpha value of breast cancer patients was 15.9 +/- 0.9 pg/mL while it was 5.8 +/- 1.7 pg/mL in the control group; the difference was statistically significant (p < 0.0001). The serum levels of TNF-alpha were markedly decreased in patients with partial and complete responses compared to pre-treatment values (p < 0.0001). There was also a difference in TNF-alpha levels in patients with partial vs complete responses (p < 0.0001). The relative change between pre- and post-treatment values correlated significantly with the type of response (p = 0.004). These results suggest that the serum concentration of TNF-alpha can be an indicator of response and could be used in clinical decision-making for patients with locally advanced breast cancer.     

Does N‐acetyl Cystein Affect the Sensitivity and Specificity of Helicobacter pylori Stool Antigen Test?

Background. N‐acetyl cystein, a mucolytic agent, might make Helicobacter pylori antigens shed more easily to stool, and might therefore contribute to the diagnostic accuracy of the Helicobacter pylori stool antigen test. The aim of this study is to investigate if N‐acetyl cystein contributes to the diagnostic accuracy of the Helicobacter pylori stool antigen test by increasing the sensitivity and specificity of the test. Materials and Methods. 107 patients were separated into treatment and placebo groups. The AC group (n = 53) was given 5 ml of acetyl cystein (4%) t.i.d. and the Placebo group (n = 54) was given placebo, for 3 days. Helicobacter pylori status was determined by both histology and CLOtest. Stool samples were assayed using a specific ELISA kit for Helicobacter pylori stool antigen. Results. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of Helicobacter pylori stool antigen test were 76%, 79%, 90%, 55%, and 77%, respectively, in AC group; and 85%, 89%, 93%, 76% and 86%, respectively, in placebo group. Conclusions. N‐acetyl cystein did not increase, and actually decreased, the sensitivity and specificity of the Helicobacter pylori stool antigen test according to our results. We believe that this finding can be taken into consideration when setting up the exclusion criteria for future studies, which will use Helicobacter pylori stool antigen tests.     

Reliability and efficiency of interphase-fish with alpha-satellite probe for detection of aneuploidy

Early diagnosis is very important in pre- and postnatal diagnosis of Down syndrome. This study examines the use of fluorescence in situ hybridization (FISH) to detect trisomy 21 in interphase nuclei and metaphase chromosome obtained from fifty-four Down syndrome patients with a regular type trisomy 21. Three of them showed six hybridization signals on both interphase nuclei and metaphase spreads instead of five signals corresponding to two chromosomes 13 and three chromosomes 21 although they were cytogenetically trisomy 21. Simultaneous application of probe combination revealed that one of the extra signals of chromosomes 13/21 a-satellite probe was located on chromosome 22 in two cases and one extra signal on chromosomes 15 in one case. In addition, another case showed four hybridization signals on both interphase nuclei and metaphase spreads instead of five signals, indicating deletion of the chromosome specific alpha-satellite DNA sequence of chromosome 13/21. These centromeric sequence changes may have pathological significance in the appearance of aneuploidy because they may be involved in the important centromere function.     

Tissue and concentration-dependent effects of sodium selenite on muscle contraction

In this study, we demonstrated that sodium selenite with high doses (≥ 10^-3 M) were potent in inducing a contracture type effect on heart and smooth muscles. Selenite (Se), at a concentration of 10^-3 M, caused a contracture effect in heart preparations. Also, low Se concentrations did not have any significant effect. Although low concentrations of Se (≥ 10^-5 M) had a biphasic effects on acetylcholine (ACh) induced and spontaneous ileum contractions, 10^-3 M selenite enhanced once more a contracture effect similar to that of the heart preparations. Replacing Ca²⁺ concentration of the bathing solution by twofold Ca²⁺ or Ca²⁺-free did not change the effects of selenite (10^-5 M) on contractility of ileum preparations. In vascular smooth muscle, low concentration of selenite (<10^-4) had no significant effects on KC1, and phenylephrine-induced contractions and acethylcholineinduced endothelium-dependent relaxations of isolated rabbit aorta. However, the contractions induced by phenylephrine and the relaxations induced by acetylcholine in rabbit aorta were depressed significantly by high concentration of selenite (10^-3 M). The results obtained by selenite exposure from these three different types of tissue preparations first suggest that the high concentration of selenite exposure induces some alterations in the functions of muscles and endothelium in a tissue and dose-dependent manner. Second, this observed irreversible type of dysfunction of tissues induced by l0^-3 M selenite is not directly dependent on the Ca²⁺ entrance into the cytosol, but might be induced by the increase of intracellular Ca²⁺ with the disturbance of Ca²⁺ regulation.     

In vivo evidence suggesting a role for purine-catabolizing enzymes in the pathogenesis of cisplatin-induced nephrotoxicity in rats and effect of erdosteine against this toxicity

The aim of this experimental study was to investigate the possible role of adenosine deaminase (AD) and xanthine oxidase (XO) in the pathogenesis of cisplatin-induced nephrotoxicity and the effect of erdosteine in decreasing the toxicity. The intraperitoneal injection of cisplatin (7 mg kg(-1) body weight) induced a significant increase in plasma creatinine level and blood urea nitrogen (BUN), and plasma and damaged renal tissue activities of AD and XO in rats. Co-treatment with erdosteine (10 mg kg(-1)day(-1)) attenuated the increase in the plasma creatinine and BUN levels, and significantly prevented the increase in tissue and plasma AD and XO activities (P<0.05). The results of this study revealed that XO and AD may play an important role in the pathogenesis of cisplatin-induced nephrotoxicity. The potent free radical scavenger erdosteine may have protective potential in this process and it will become a promising drug in the prevention of this undesired side-effect of cisplatin, but further studies are needed to illuminate the exact protection mechanism of erdosteine against cisplatin-induced nephrotoxicity.     

Evidence of relaxant effect of omeprazole in rabbit corpus cavernosum in vitro

The present experiments were designed to investigate the effects of omeprazole, a H(+)-K+ ATPase inhibitor, on corporal smooth muscle tone in vitro. All spontaneous contractile activity in the corpus cavernosum was blocked following omeprazole (0.1 mM-1 mM) administration. However atropine (1 microM), Nw-nitro L-arginine methyl ester (L-NAME, 30 microM) or indomethacin (10 microM) did not affect the spontaneous contraction. Omeprazole (10 microM-1 mM) concentration-dependently induced relaxation in corporal smooth muscle precontracted with 10 microM phenylephrine or 80 mM KCl. Pretreatment of corporal tissue with L-NAME (30 microM), indomethacin (10 microM), ammonium chloride (7.5 mM), sodium acetate (7.5 mM), tetraethyl ammonium chloride (0.5 mM) or glibenclamide (1 microM) had no effect on the omeprazole induced relaxant responses. Nimodipine, an L-type Ca++ channel blocker, relaxed corporal strips precontracted with 80 mM KCl. Collectively, these results indicate that the inhibition of spontaneous contraction and the relaxation of precontracted corporal smooth muscle by omeprazole is probably mediated by the blockade of calcium channels. Further work is needed to determine the cellular mechanism(s) of action by which omeprazole acts on corpus cavernosum smooth muscle.     

Plasma values of oxidants and antioxidants in acute brain hemorrhage

The levels of oxidants xanthine oxidase (XO), nitric oxide (NO), and malondialdehyde (MDA) and of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GRD) were determined in plasma within 24 h after onset of hemorrhagic stroke in 17 patients (9 men and 8 women, aged 60.7+/-11.5 yr) and in 20 healthy controls (12 men and 8 women, aged 62.5+/-8.3 yr). Compared to controls, the plasma SOD and total superoxide scavenger activities (TSSA) were significantly lower and the NO levels were significantly higher among the stroke patients. XO showed a slight, nonsignificant increase in the patients, but the levels of MDA, NSSA, GRD, and GSH-Px did not show any significant differences between the two groups. The hemorrhage volume was negatively correlated with the initial score of the Glasgow Coma Scale and a positive correlation with lethal outcome, but it did not correlate significantly with any of the measured parameters. The results suggest that free radicals might play a role in the development of brain injury following brain hemorrhage.