Tachykinin receptor (NK(1), NK(2), NK(3)) binding sites in the rat caudal brainstem following neonatal capsaicin administration

Binding of [125I]-Bolton-Hunter substance P ([125I]-BHSP), [125I]-neurokinin A and [3H]-senktide to tachykinin NK(1), NK(2) and NK(3) receptors, respectively, was examined in caudal brainstem sections of 10-week-old rats pretreated as neonates (P2) with capsaicin (50 mg/kg, s.c.) or vehicle. [125I]-BHSP binding was localised to the nucleus of the solitary tract (NTS), hypoglossal nucleus and inferior olivary complex, whereas [125I]-neurokinin A and [3H]-senktide binding were confined to the NTS. The distribution and density of binding sites were similar in vehicle- and capsaicin-pretreated rats, suggesting that sensory neuron ablation by neonatal capsaicin does not affect tachykinin receptor numbers in the rat caudal brainstem.     

Unusual presentation of perirenal lung metastases

Lung cancer is not commonly known to metastasise to the perirenal space, with only five such cases previously published. We present an unusual case of perirenal lung metastases manifesting as diffuse perinephric stranding which to our knowledge has not been described before.     

Noonan's and DiGeorge syndromes with monosomy 22q11

A boy with the dysmorphic features of Noonan's syndrome and pulmonary valve stenosis who had evidence of hypoparathyroidism and abnormal T lymphocyte numbers in the neonatal period is reported. He had a normal karyotype but molecular analysis revealed a submicroscopic deletion within chromosome 22q11, the region deleted in DiGeorge syndrome. Thus this child has both Noonan's syndrome and DiGeorge syndrome; 22q11 is a candidate region for a gene defective in Noonan's syndrome.     

Review of dilated cardiomyopathies. Dilated cardiomyopathies and altered prothrombotic state: a point of view of the literature

Heart failure is an enormously important clinical problem that, if not faced, may overwhelm health care resources. Primary and secondary cardiomyopathies cause the majority of cases of clinical heart failure, which is thus better approached from the utility point of view of myocardial failure. Furthermore, the risk of thromboembolic complications presenting in such disease may be higher than in ischemic cardiomyopathy. Intracardiac thrombi and mural endocardial plaques (from the organization of thrombi) are present at necropsy in more than 50% of patients with dilated cardiomyopathy (DCM). Several studies have shown that systemic and pulmonary emboli are more frequent in patients with ventricular thrombi or plaques. Dilated cardiomyopathy has been associated with left ventricular thrombosis which leads to substantial morbidity and mortality as a site for peripheral emboli. There are some studies on patients with dilated cardiomyopathy showing altered hemostasis and platelet behavior despite sinus rhythm. Platelet activation, thrombin activation and fibrinolytic activity are increased in patients with DCM compared to normal subjects. However, these markers reflecting coagulation activation in patients with left ventricle thrombus are comparable to those in patients without thrombus in the left ventricle. The pathophysiology and clinical issues concerning the susceptibility to develop left ventricular (LV) thrombosis and its complications like cerebrovascular disease in patients with DCM are summarized and the most recent articles present in the medical literature are reviewed.     

Subthalamic stimulation activates internal pallidus: evidence from cGMP microdialysis in PD patients

Parkinson's disease patients benefit from deep brain stimulation (DBS) in subthalamic nucleus (STN), but the basis for this effect is still disputed. In this intraoperative microdialysis study, we found elevated cGMP extracellular concentrations in the internal segment of the globus pallidus, despite negligible changes in glutamate levels, during a clinically effective STN-DBS. This supports the view that a clinically beneficial effect of STN-DBS is paralleled by an augmentation (and not an inactivation) of the STN output onto the GPi.     

Clinical understaging in patients with prostate adenocarcinoma submitted to radical prostatectomy: predictive value of serum chromogranin A

PURPOSE: To evaluate whether the pretreatment determination of serum chromogranin A (CgA) can provide information beyond that obtained with serum prostate specific antigen (PSA) and Gleason score at biopsy as a predictive factor of clinical understaging (T2-pT3) of prostate adenocarcinoma. MATERIALS: In this prospective study, we analyzed 83 consecutive patients with clinical T2N0M0 prostate adenocarcinoma submitted to radical prostatectomy (RRP). On the same day of RRP, before surgery, a blood sample for the determination of serum total PSA and CgA levels (RIA) was obtained. RESULTS: After RRP, 27 of the 83 cases (32.5%) showed extracapsular disease extension (pT3) at the final pathological examination and were considered clinically understaged. A significant association between serum CgA and pathological stage (r = 0.3830; P = 0.0004) was found. At the multivariate analysis, serum CgA and PSA, but not biopsy Gleason score, were found to be significant pretreatment independent predictors of pT3 at RRP (P = 0.00004 and P = 0.0018, respectively). The relative risk of clinical understaging significantly varied according to serum CgA levels. Using a CgA cut-off value of 60 ng/ml, PPV and NPV for clinical understaging were 0.5161 and 0.7885, respectively (P = 0.0072). CONCLUSIONS: Serum CgA could be incorporated into risk assessment models of newly diagnosed prostate cancer.     

An uncleavable form of pro-scatter factor suppresses tumor growth and dissemination in mice

Scatter factor (SF), also known as hepatocyte growth factor, is ubiquitously present in the extracellular matrix of tissues in the form of an inactive precursor (pro-SF). In order to acquire biological activity, pro-SF must be cleaved by specific proteases present on the cell surface. The mature form of SF controls invasive cues in both physiological and pathological processes through activation of its receptor, the Met tyrosine kinase. By substituting a single amino acid in the proteolytic site, we engineered an unprocessable form of pro-SF (uncleavable SF). Using lentivirus vector technology, we achieved local or systemic delivery of uncleavable SF in mice. We provide evidence that (a) uncleavable SF inhibits both protease-mediated pro-SF conversion and active SF-induced Met activation; (b) local expression of uncleavable SF in tumors suppresses tumor growth, impairs tumor angiogenesis, and prevents metastatic dissemination; and (c) systemic expression of uncleavable SF dramatically inhibits the growth of transplanted tumors and abolishes the formation of spontaneous metastases without perturbing vital physiological functions. These data show that proteolytic activation of pro-SF is a limiting step in tumor progression, thus suggesting a new strategy for the treatment or prevention of the malignant conversion of neoplastic lesions.