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BACKGROUND: Current approaches for detecting circulating tumour cells (CTCs) in blood are dependent on CTC enrichment and are based either on surface epithelial markers on CTCs or on cell size differences. The objectives of this study were to develop and characterise an ultrasensitive multiplex fluorescent RNA in situ hybridisation (ISH)-based CTC detection system called CTCscope. This method detects a multitude of tumour-specific markers at single-cell level in blood. METHODS: Healthy blood samples spiked with tumour cell lines were used as a model system for the development and initial characterisation of CTCscope. To demonstrate the feasibility of CTC detection in patient blood, duplicate blood samples were drawn from 45 metastatic breast cancer patients for analysis by CTCscope and the CellSearch system. The association of CTCs with the tumour marker CA15-3 and progression-free survival (PFS) were assessed. RESULTS: CTCscope detected CTC transcripts of eight epithelial markers and three epithelial-mesenchymal-transition (EMT) markers for increased sensitivity. CTCscope was used to detect CTCs with minimal enrichment, and did not detect apoptotic or dead cells. In patient blood samples, CTCs detected by CellSearch, but not CTCscope, were positively correlated with CA15-3 levels. Circulating tumour cells detected by either CTCscope or CellSearch predicted PFS (CTCscope, HR (hazard ratio) 2.26, 95% CI 1.18-4.35, P=0.014; CellSearch, HR 2.50, 95% CI 1.27-4.90, P=0.008). CONCLUSION: CTCscope offers unique advantages over existing CTC detection approaches. By enumerating and characterising only viable CTCs, CTCscope provides additional prognostic and predictive information in therapy monitoring.

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PURPOSE: Breast cancer is associated with adverse outcomes in patients with the metabolic syndrome phenotype. To study this further, we examined the relationship between serum metabolite levels and the components of metabolic syndrome with treatment outcomes in breast cancer. METHODS: A total of 88 women with measurable breast cancer were studied; their serum metabolites as assessed by (1)H nuclear magnetic resonance spectroscopy, blood pressure, lipids, glucose, body mass index and waist circumference were recorded and correlated with treatment response. RESULTS: We identified metabolic syndrome in approximately half of our cohort (42 patients) and observed a significant trend (P = 0.03) of increased incidence of metabolic syndrome in partial response (33.3%), stable disease (42.9%) and progressive disease groups (66.1%). High blood sugar predicted a poor response (P < 0.001). Logistic regression of metabonomic data demonstrated that high lactate (P = 0.03) and low alanine (P = 0.01) combined with high glucose (P = 0.01) were associated with disease progression. CONCLUSIONS: Metabolic syndrome is commonly observed in metastatic breast cancer and these patients have poorer outcomes. These data, which support our previous findings, suggest that high blood glucose as part of metabolic syndrome is associated with a poor response in breast cancer. They also validate new therapeutic approaches that focus on metabolism.

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The method for the calculation of correction factors is presented, which can be used for the assessment of the mean annual radon concentration on the basis of 1-month or 3-month indoor measurements. Annual radon concentration is an essential value for the determination of the annual dose due to radon inhalation. The measurements have been carried out in 132 houses in Poland over a period of one year. The passive method of track detectors with CR-39 foil was applied. Four thermal-precipitation regions in Poland were established and correction factors were calculated for each region, separately for houses with and without basements.

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A heart concussion contusion is a dangerous and rare nosological entity. A case of 37 years old woman with heart concussion/contusion and other injuries, developed as consequence of fall from the height, was presented. An attempt to explain define term of heart concussion and contusion was made.

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UNLABELLED: The aim of the study was to determine what is the correlation between immunological phenomena and pathological changes in chronic gastritis and how it refers to the histology and endoscopy. PATIENTS AND METHODS: 42 patients with dyspepsia underwent following procedure: 1) gastroscopy and antral biopsy of 3 specimens; 2) histology; 3) immunofluorescence of the specimens in purpose to detect bound immunoglobulins using antibodies anti-human IgA + IgG + IgM labelled with rhodamine; 4) serologic test for anti-H.pylori antibodies. The research included 17 females and 25 males (ages 30-86, median 53.4 +/- 15.47). The obtained data were compared referring to mutual correlations and presented according to the kind of pathological changes depending on:--presence or absence of Helicobacter pylori infection;--presence or absence of anti-Helicobacter pylori antibodies;--presence or absence of lymphocytic infiltration;--presence or absence of bound immunoglobulins in gastric mucosa. RESULTS: --We have not observed ulcerations in anti-Helicobacter pylori seronegative group;--intestinal metaplasia and gastric ulcer were more frequent in bound immunoglobulins positive group;--biliary reflux was observed less frequently in lymphocyte infiltration negative group then in the positive one. CONCLUSION: pathological changes in chronic gastritis may depend not only on the presence of Helicobacter pylori infection, but also on the presence and quality of immunological response on its antigens.

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Immunological response against myocardial antigens was assessed in 12 patients (pts) (9 males, 3 females, aged 24-62 years) with aortic homografts (AH) and 36 pts (29 males, 7 females, aged 26-61 years) with aortic valve prostheses (AVP). In all pts a titre of anti-myocardial antibodies, a concentration of free-circulating immune complexes and leucocytes migration inhibition test with myocardial antigen were assessed before operation and 1, 12, 24 months after operation. In 20 pts with AH immunological humoral response against HLA antigens was evaluated. After the operation pathological indexes of immunological response against myocardial antigens were observed both in pts with AH as in pts with AVP. The mean titre of anti-myocardial antibodies before operation was in both groups between 1:4 and 1:8, and 1 month after operation between 1:32 and 1:64. In 12 and 24 months after operation the mean titre in AH and AVP group was respectively 1:8 and 1:4. Before operation pathological concentration of immune complexes (> 0.084 mg/ml) was observed in 17% AH and 11% AVP pts. Pathological elevation of immune complexes 1, 12 and 24 months after operation was observed respectively in AH and AVP group in 58%, 42%, 33% and 67%, 50%, 42%. Leucocyte migration inhibition index was pathological (< 0.8) before operation in 58% in both groups, and 1, 12, 24 months after operation was pathological in AH and AVP group respectively in 67%, 17%, 17% and 61%, 33%, 31%. In most pts of both groups immunological response against myocardial antigens was transient and was terminated up to 12-24 months after operation.(ABSTRACT TRUNCATED AT 250 WORDS)

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HLA antigens A, B, C were determined in 61 patients with aortic valve disease and in 263 healthy controls. The patients were divided into two subgroups--with rheumatic fever in anamnesis (N = 24) and without (N = 37). In the whole group of patients with aortic valve disease there was a lower frequency of incidence of HLA A3 in comparison to the control group. In the subgroup with rheumatic fever in anamnesis there was a deficit of HLA A3 and a much more frequent incidence of HLA B17, in the subgroup without rheumatic fever a more frequent incidence of HLA A2, A9, A28, B15 was noted in comparison to the control group. This study shows that in 60% of patients with aortic valve disease the etiology is linked not to rheumatic fever but probably to a connective tissue disorder. A deficit of HLA A3 and presence of B17 can be a risk factor for rheumatic fever.

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Transvenous ablation of atrioventricular (AV) junction is an accepted method for treatment of refractory supraventricular arrhythmias. In the classic method the proper position of the ablation electrode is based on registration of the potentials of the conduction system. However according to Bredykis et all. Localization of the catheter is also possible under fluoroscopic control. The study presents a 67-year old patient with recurrent supraventricular tachycardias. Repeated bouts of arrhythmia, refractory to various antiarrhythmic drugs, caused severe hemodynamic consequences. Several cardioversions were performed for arrhythmia termination. Electrophysiologic study using transesophageal pacing showed a concealed accessory pathway conducting only in retrograde direction and the patient was designated for transvenous ablation of AV junction. The specially developed 6F USCI electrode with enlarged tip was used. The catheter was introduced into the right ventricle under fluoroscopic control and then slowly withdrawn until the tip was placed within the tricuspid valve at the border of atrium and ventricle. Cathodal pole of the defibrillator was connected with the electrode. Then the procedure was similar to the classic ablation. Single 200 joules DC shock caused complete AV block. No complications were seen during and after the procedure. A permanent cardiac pacemaker was implanted at the 4th day after ablation. The patient was doing well, without medication and no arrhythmias were observed during the 9 month period. The AV block persisted stable, also retrograde conduction was absent.

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We determined the minimum number of hours per day of testosterone (T) exposure required to activate male sexual behavior, and correlated these changes with the temporal parameters of androgen receptor occupation. For the first part of the study, castrated Long-Evans male rats received two 10 mm T-filled Silastic capsules in open flank pouches for 4, 8, 12, 16, 18, 21, or 24 hours per day over a 10 day period. Tests for male sexual behavior were conducted on days 2-3, 4-5, 7-8, and 9-10 of T treatment. A significantly higher proportion of males receiving 21 or 24 hr of daily T exposure mounted, intromitted and ejaculated compared to groups with daily T exposures of 18 hr or less. In the second part of this study we assessed whether it was necessary to maintain high levels of androgen receptor occupation during the 21-24 hr exposure period in order to activate male sexual behavior. Cell nuclear androgen receptor occupation was measured in HPAS (combined hypothalamus, preoptic area, amygdala and septum) of rats receiving 12, 21, or 24 hr of T exposure. In all three groups, nuclear androgen receptor occupation was high at the time of capsule removal, and fell significantly by 3 hr following T capsule removal. By 6 hr after T capsule removal, androgen receptor binding had fallen to castrate levels. These results demonstrate that, although relatively brief (less than or equal to 18 hr/day) exposures to testosterone can activate mounts and intromissions, significantly more responses are found in males receiving at least 21 hr of T exposure per day.(ABSTRACT TRUNCATED AT 250 WORDS)

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In these experiments we examined the relationship between olfactory bulb removal, limbic system androgen receptor binding and male copulatory behavior. Sexually experienced male rats were castrated, and implanted with two 10 mm testosterone-filled silastic capsules. Animals then underwent either bilateral olfactory bulb removal (BOB) or sham surgery (Sham). Beginning 1-2 days postoperatively both BOB and Sham operates were given 4 tests for male copulation on alternate days. Less than 40% of BOB males ejaculated. In contrast, 80-100% of sham operates continued to ejaculate throughout the 4 postoperative tests. Cell nuclear androgen receptor binding was assessed in amygdala, hypothalamus, preoptic area and septum 1-2 and 8-9 days after either bulbectomy or sham surgery. We found that olfactory bulbectomy significantly reduces androgen receptor binding in amygdala and hypothalamus. The reduction in androgen receptor binding in amygdala occurs within 1-2 days following olfactory bulb removal and is correlated with the disruption of ejaculatory activity. These data suggest that the neuromodulation by olfactory bulb input to androgen-concentrating neurons in the amygdala and hypothalamus is necessary for effective copulation in male rats.

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