Explosive-aggressive behavior related to bilateral subthalamic stimulation

We describe a patient with Parkinson's Disease who underwent bilateral subthalamic nucleus deep brain stimulation and later presented with episodes of aggressive behavior disorder with disturbed impulse control and an inability to control anger likely related to the deep brain stimulation "switch-on stimulation". We hypothesize that increasing voltage intensity could influence neighboring passing fibers coming from basal limbic system that are involved in the regulation of affect and emotional behavior. We suggest investigating these neuropsychological disturbances considering their influence on quality of life after surgery.     

Large waist circumference and risk of hypertension

OBJECTIVE: To examine the relationship between 24 h ambulatory blood pressure monitoring and three commonest anthropometric measurements for obesity--body mass index (BMI), waist-to-hip ratio (WHR) and waist circumference (W). DESIGN: Cross-sectional survey among outpatients at the Obesity Research Center. SUBJECTS AND METHODS: Four-hundred and sixty-one overweight or obese subjects, non-diabetic, otherwise healthy, aged 20-70 y, of either sex, were consecutively recruited. All subjects underwent 24 h ambulatory blood pressure monitoring. The population study was separated in normotensive and hypertensive males and females and the possible risk factors for hypertension (W, WHR, BMI and age) were subdivided into different classes of values. RESULTS: Logistic regression shows that W is the most important anthropometric factor associated with the hypertensive risk. Among males with W> or =102 cm the odds ratio (OR) for hypertension is three times that of males with W<94 cm using casual BP measure (OR 3.04), nearly four times higher using 24 h BP mean (OR 3.97), and even five times higher using day-time BP mean (OR 5.19). Females with W> or =88 cm have a risk for hypertension twice that of females with W<80 cm, whatever BP measurement was take (casual, 24 h or day-time). Males with WHR> or =0.96 and females with WHR> or =0.86 show significant OR for hypertension only by 24 h BP measurement and by day-time BP measurement. BMI seems to have no significant relationship to hypertensive risk. Age shows a significant relationship to hypertensive risk only considering males aged > or =55 y and females aged > or =50 y. CONCLUSION: The waist circumference seems to have a strong association with the risk of hypertension, principally by the ambulatory BP monitoring, when compared with casual BP measurement.     

Role of NRAS mutations as prognostic and predictive markers in metastatic colorectal cancer

NRAS mutations occur in 3–5% of colorectal cancer. Differently from KRAS and BRAF mutations, the role of NRAS mutations as prognostic and predictive markers in metastatic colorectal cancer (mCRC) has been investigated to a lesser extent. A retrospective series suggested the role of NRAS mutations as predictors of resistance to anti‐EGFR monoclonal antibodies (MoAbs) in chemo‐refractory patients with mCRC. In our study, KRAS codons 12, 13, 61 and BRAF codon 600 mutational status were evaluated in mCRCs referred to our Institution from 2009 to 2012. NRAS codons 12, 13 and 61 mutational status was analyzed in KRAS/BRAF wt patients. We collected pathological and clinical features in the overall population and outcome data in a subset of NRAS mutated chemo‐refractory patients treated with anti‐EGFR MoAbs in advanced lines. NRAS was mutated in 47/786 (6%) mCRCs. NRAS and KRAS mutated tumors did not show significant differences in terms of clinical and pathological characteristics, except for a lower prevalence of mucinous histology (p = 0.012) and lung metastases (p = 0.012) among NRAS mutated tumors. In the uni‐ and multivariate model, NRAS mutations were associated with shorter overall survival (OS) compared to all wt patients (median OS 25.6 vs 42.7 months; univ: HR = 1.91, 95% CI 1.39–3.86, p = 0.0013; multiv: HR = 1.75, 95% CI 1.1.3–2.72, p = 0.013). None of the chemo‐refractory NRAS mutated patients evaluable for response to anti‐EGFRs achieved response. In conclusion, NRAS mutations have a relevant incidence in patients with mCRC and showed an association with specific clinical and pathological features. NRAS mutations affect mCRC patients' prognosis and predict lack of response to anti‐EGFRs.     

Novel Axl-driven signaling pathway and molecular signature characterize high-grade ovarian cancer patients with poor clinical outcome

High-grade epithelial ovarian cancer (HGEOC) is a clinically diverse and molecularly heterogeneous disease comprising subtypes with distinct biological features and outcomes. The receptor tyrosine kinases, expressed by EOC cells, and their ligands, present in the microenvironment, activate signaling pathways, which promote EOC cells dissemination. Herein, we established a molecular link between the presence of Gas6 ligand in the ascites of HGEOCs, the expression and activation of its receptor Axl in ovarian cancer cell lines and biopsies, and the progression of these tumors. We demonstrated that Gas6/Axl signalling converges on the integrin β3 pathway in the presence of the adaptor protein p130Cas, thus inducing tumor cell adhesion to the extracellular matrix and invasion. Accordingly, Axl and p130Cas were significantly co-expressed in HGEOC samples. Clinically, we identified an Axl-associated signature of 62 genes able to portray the HGEOCs with the shortest overall survival. These data biologically characterize a group of HGEOCs and could help guide a more effective therapeutic approach to be taken for these patients.     

Increased killer cell activity in insulin dependent (Type 1) diabetes mellitus

Summary Antibody dependent cell mediated cytotoxicity in relation to the levels of circulating killer cells was investigated in 16 newly diagnosed classical insulin dependent (Type 1) diabetics, 11 islet cell antibody positive non diabetic children with at least one HLA haplotype in common with their diabetic sibling, and in 15 normal controls. Antibody dependent cell mediated cytotoxicity was evaluated using, as target, ⁵¹Cr labelled human 0⁺ erythrocytes sensitised with an anti-CD antiserum. Killer cells were measured by the low affinity E-rosetting cell technique. Increased killer cell levels (>normal mean + 2SD) were accompanied by a significant enhancement in antibody dependent cell mediated cytotoxicity both in newly diagnosed diabetics (p < 0.05) and in unaffected siblings (p < 0.01). These preliminary results indicate that raised antibody dependent cell mediated cytotoxicity is a feature of insulin dependent diabetes at diagnosis and suggest that active B cell damage might be occurring some time before the onset of clinical symptoms.     

A new cell line from human infiltrating ductal carcinoma of the breast: establishment and characterization

We established a novel cancer cell line (MAST) from the ascitic fluid of a metastatic infiltrating ductal carcinoma of the breast. The epithelial and neoplastic nature of the MAST cells was confirmed by ultrastructural analysis. The cell line was maintained as a monolayer with a doubling time of about 68 h, and it possessed an abnormal karyotype with a modal chromosome number of 60, a trisomy of chromosome 18 and other unidentified rearranged chromosomes. Among the markers consistently found in MAST metaphases, we noted a t(14; 14) and a very large subtelocentric, a large satellited acrocentric and a very large submetacentric chromosome with striking fluorescent bands. Immunoenzymatic assay demonstrated that the MAST cell line was positive for estrogen and progesterone receptors. The in vitro drug-sensitivity assay showed a marked resistance of the cell line to 5-fluorouracil and 4-hydroperoxycyclophosphamide and a moderate resistance to etoposide and 4-epidoxorubicin. The molecular analysis showed a four- to sixfold amplification of the c-myc gene and no amplification or rearrangement of theint-2, c-erbB-2, c-Ha-ras, c-mos andhst-1 genes.     

Comparison of ultrasonic scanning and scintiscanning in the evaluation of thyroid hemiagenesis

Seven female subjects in whom thyroid hemiagenesis was suspected on the basis of clinical findings and scintiscanning before and after TSH administration were studied with ultrasound. Ultrasonic scanning confirmed true hemiagenesis in only three cases. In the other four it revealed a nonfunctional hypoplastic lobe contralateral to the assumed single lobe.     

Vohwinkel syndrome (mutilating keratoderma) associated with craniofacial anomalies

We describe a female patient with Vohwinkel syndrome (mutilating palmoplantar keratoderma), who in addition showed cleft lip and palate, microcephaly, facial asymmetry, and other anomalies. © 1994 Wiley-Liss, Inc.     

Long-term treatment with fenfluramine in obese subjects

The effect of fenfluramine, an anorectical drug, given for nine months to a group of 156 obese subjects, on body-weight and adipose mass reduction as well as on glucose tolerance, has been studied. Subjects were divided in four different groups according to various protocols of therapy: the first group took the drug once a day in a single 60 mg dose in the morning; the second group received the drug once a day in a single 40 mg dose in the morning; the third group took the drug divided in three equal daily doses and the last group was treated with diet alone. During the first three months of treatment, fenfluramine 60 mg, given both in a single dose in the morning and divided in three equal daily doses, combined with diet, produces a significant body-weight reduction in comparison with the group of obese subjects treated with diet alone. In the following three months, it was possible to document a further body weight loss in all subjects, whatever the group to which they were assigned. At the end of the sixth month of observation, only slight differences could be demonstrated among the groups as regards the body-weight and adipose mass decrease. In addition the results failed to demonstrate a statistically different weight loss when the drug as administered in a single dose in the morning, compared with the conventional treatment of three times a day. No significant improvement of glucose tolerance was documented. In conclusion, in long-term treatment with fenfluramine, in contrast with short-term studies, no direct effect of this drug on body-weight and adipose mass decrease was demonstrated.