Does the Incredible Years Teacher Classroom Management programme improve child–teacher relationships in childcare centres? A 1-year universal intervention in a Norwegian community sample

European Child & Adolescent Psychiatry - The Incredible Years Teacher Classroom Management (IY TCM) programme has shown promise in reducing behaviour problems among high-risk children in...     

Effect of acetylcysteine on prothrombin index in paracetamol poisoning without hepatocellular injury

Acetylcysteine treatment reduces liver damage after paracetamol overdose, but can affect the prothrombin index, which is used to assess the progress of overdose patients. We aimed to assess retrospectively the effect of intravenous acetylcysteine on the prothrombin index in patients with paracetamol poisoning without signs of hepatocellular injury. Prothrombin index had been recorded before, and serially during, acetylcysteine treatment in 87 patients. After initiation of treatment, prothrombin index decreased (mean 0.33, 95% CI 0.29-0.38) in all patients, and was strongly associated with the start of acetylcysteine infusion. In patients with uncomplicated paracetamol poisoning, a fall in this index might be misinterpreted as a sign of liver failure, leading to prolonged treatment time.     

Type 1 protein tyrosine kinases in benign and malignant breast lesions

Aims : To determine their significance, we examined the expression pattern of the four epidermal growth factor receptor (EGFR) family members as well as the phosphotyrosine kinase activity in breast tumour tissues.  

Methods and results

Fifty-three malignant breast tumours, four breast cancer cell lines, and 10 benign breast tumours were investigated. Fifty-three per cent (28/53) of the malignant tumours expressed EGFR protein, and the majority of these positive tumours were strongly positive. Eighty per cent (8/10) of the benign tumours also expressed EGFR protein, but all in a lower or moderate level. An association between EGFR expression and increasing malignancy grade was found in the group of infiltrating ductal carcinomas. Of the malignant tumours, 35.8% (19/53) expressed c-erbB-2 protein and 17% (9/53) c-erbB-3 protein, while no expression of c-erbB-2 and c-erbB-3 proteins was found in the benign tumours. Contrary to previous reports, we observed c-erbB-4 receptor protein to be less expressed in the malignant breast tumours. The 'normal' breast epithelial cells adjacent to the malignant tumours and the benign tumours demonstrated intensified membrane staining for c-erbB-4, while a number of the malignant tumours demonstrated a weak cytoplasmic staining or were negative. However, several malignant tumours with strong membrane staining for the c-erbB-4 protein were also found. No simple association between the expression of the four receptors and phosphotyrosine kinase activity was found.  

Conclusion

Our study has revealed a complex expression pattern of the EGFR family members in breast tumour cells. While the data about EGFR, c-erbB-2, c-erbB-3 and phosphotyrosine are largely in line with what has been reported, we found the c-erbB-4 protein expression to be decreased in the malignant tumours.     

Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas.

Fifty-nine primary breast carcinomas and 11 metastases were examined to identify genetic alterations in the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q. Loss of heterozygosity (LOH) was frequently observed on chromosome arms 17p (p144D6 lost in 75%, pYNZ22.1 in 55%, and TP53 in 48% of the primary tumours), 13q (RBI lost in 40% of the primary tumours), and 17q (pRMU3 lost in 35%, pTHH59 in 29%, and NM23HI in 26% of the primary tumours). Loss of all the markers except p144D6 was observed even more frequently in the metastases. Pairwise comparisons for concordance of allele losses on 17p indicated that there might be two genes on 17p implicated in breast cancer development; the TP53 gene and a gene located close to the p144D6 and pYNZ22.1 markers. LOH of the RBI gene was associated with LOH of pYNZ22.1 and p144D6, but not with LOH of TP53. LOH of RBI and TP53 was associated with occurrence of ductal carcinomas, RBI and p144D6 losses with tumour size, and p144D6 losses with positive node status as well. LOH of TP53 and the three 17q markers NM23HI, pTHH59, and pRMU3 was most frequently observed in tumours from postmenopausal women. p144D6 losses occurred most frequently in progesterone receptor-negative tumours, whereas pTHH59 losses occurred most frequently in oestrogen receptor-negative tumours. LOH of the investigated loci was not associated with ERBB2 protooncogene amplification, with positive family history of breast cancer, or with survival.     

Perfusion characteristics and norepinephrine reactivity of human renal carcinoma

Kidneys, surgically removed due to carcinoma, were subjected to perfusion in vitro. The perfusion distribution was studied by means of labeled microspheres injected during maximal vascular dilation and during two different norepinephrine concentrations. The perfusion concluded with injection of barium sulfate. Two-mm-thick slices of tissue were autoradiographed and microangiographed for visualization of perfusion and distribution of vascular density, respectively. Multiple specimens from tumor and cortical tissues were subjected to quantitative perfusate flow analysis. In spite of regionally high vascular density, perfusion through "normal-sized" capillaries was very low in tumor tissue as compared to cortex (during maximal dilation, one-tenth of the cortical flow). During moderate norepinephrine infusion, the perfusate flow decreased, and the resistance of the cortex increased. The flow to tumor tissue increased while the vascular resistance remained constant. During higher norepinephrine concentrations, the flow was redistributed; i.e., the cortical flow increased while that of the tumor decreased, due to a marked increase in tumor vascular resistance while the cortical tissue showed a very moderate rise in resistance. The thin-walled tumor vessels might be collapsed under a high tissue pressure at low perfusion pressures. At higher perfusion pressure, the vessels might open up, and contractile activity may not be expressed until then. The tumor vascular resistance increased 3 to 4 times, while that of cortex showed a 7-fold increase. Indications that a considerable fraction of the perfusate passes arteriovenous passages larger than 15 micron were obtained in individual experiments, this fraction increasing upon norepinephrine infusion.     

Vascular reactivity and perfusion characteristics in 7,12-dimethylbenz(a)anthracene-induced rat mammary neoplasia

Blood flow during "resting conditions" and during noradrenaline infusion were studied by the labeled microsphere technique in dimethylbenz(a)anthracene-induced mammary tumors, skin, muscle, and lung in the rat. Intratumoral distribution of flow was studied by autoradiography of spheres trapped in the vascular beds of the tumors. Histological examination was performed and correlated to the blood flow data. Mean blood flow to the tumors during "resting conditions" was relatively high (49 ml/min/100 g tissue) but was substantially decreased (5 ml/min/100 g tissue) during noradrenaline infusion which produced a pressure elevation of 35 mm Hg. Thus, vascular resistance of the tumor tissue increased dramatically. Cardiac output increased, but total systemic resistance was unchanged. Vascular resistance in muscle was unchanged in contrast to an increase seen in skin. Shunted systemic blood flow to the lungs and bronchial arterial flow decreased indicating reactivity of abnormally large arteriovenous passages in the tumors. Poorly differentiated tumors had a higher vascular resistance than did well-differentiated tumors. Autoradiography revealed a nodular flow distribution with a slight tendency of higher perfusion in the periphery of these tumors.     

Multicenter phase II study of Nordic fluorouracil and folinic acid bolus schedule combined with oxaliplatin as first-line treatment of metastatic colorectal cancer.

PURPOSE: This Nordic multicenter phase II study evaluated the efficacy and safety of oxaliplatin combined with the Nordic bolus schedule of fluorouracil (FU) and folinic acid (FA) as first-line treatment in metastatic colorectal cancer. PATIENTS AND METHODS: Eighty-five patients were treated with oxaliplatin 85 mg/m(2) as a 2-hour infusion on day 1, followed by a 3-minute bolus injection with FU 500 mg/m(2) and, 30 minutes later, by a bolus injection with FA 60 mg/m(2) every second week. The same doses of FU and FA were also given on day 2. RESULTS: Fifty-one of 82 assessable patients achieved a complete (n = 4) or partial (n = 47) response, leading to a response rate of 62% (95% CI, 52% to 72%). Nineteen patients showed stable disease, and 12 patients had progressive disease. Thirty-eight of the 51 responses were radiologically confirmed 8 weeks later (confirmed response rate, 46%; 95% CI, 36% to 58%). The estimated median time to progression was 7.0 months (95% CI, 6.3 to 7.7 months), and the median overall survival was 16.1 months (95% CI, 12.7 to 19.6 months) in the intent-to-treat population. Neutropenia was the main adverse event, with grade 3 to 4 toxicity in 58% of patients. Febrile neutropenia developed in seven patients. Nonhematologic toxicity consisted mainly of neuropathy (grade 3 in 11 patients and grade 2 in another 27 patients). CONCLUSION: Oxaliplatin combined with the bolus Nordic schedule of FU+FA (Nordic FLOX) is a well-tolerated, effective, and feasible bolus schedule as first-line treatment of metastatic colorectal cancer that yields comparable results compared with more complex schedules.