Prognostic significance of p53 and FHIT in advanced oropharyngeal carcinoma

OBJECTIVE: To determine the prognostic significance of p53 and fragile histidine triad (FHIT) expression in advanced oropharyngeal squamous cell carcinoma. STUDY DESIGN: A retrospective collection of clinical data was correlated with the protein expression. METHOD: The expression of p53 and FHIT in specimens from patients with previously untreated advanced squamous cell carcinoma of the oropharynx was determined by immunohistochemistry. The expression of p53 and FHIT was statistically correlated with survival outcome. The primary endpoints were overall survival and disease-free survival. RESULTS: Thirty-four patients were analyzed in this study. Overexpression of p53 was observed in 41.2% (14/34) of tumors and was associated with a trend toward an improved overall survival using univariate (P =.1088, risk ratio [RR] = 0.503) and multivariate (P =.1533, RR = 0.470) analyses. Marked reduction or complete absence of FHIT expression was observed in 57.6% (19/33) of tumors. Patients with tumors showing no reduction in FHIT expression had a lower overall survival using univariate (P =.04, RR = 2.27) and multivariate (P =.013, RR = 4.41) analyses. CONCLUSION: Overexpression of p53 predicted a trend toward an improved prognosis, whereas no reduction in FHIT expression predicted a significantly poorer outcome in patients with advanced oropharyngeal cancer.     

A pilot study of nurse-led, home-based telecardiology for patients with chronic heart failure

We assessed the feasibility of home-based telecardiology for patients with chronic heart failure (CHF). Seventy-four CHF patients were enrolled into a programme of telephone follow-up and single-lead electrocardiography (ECG) monitoring. The patients transmitted their ECG data by fixed telephone line to a receiving station, where a nurse was available for an interactive teleconsultation. Patients were followed up for a mean (SD) of 307 (108) days; 1467 calls were analysed (213 ad hoc consultations and 1254 scheduled consultations). A total of 124 cardiovascular events were recorded. Modifications to therapy were suggested in response to 119 calls; hospital admissions were suggested for 13 patients, further investigations for 7 and a consultation with the patient's general practitioner for 13. No action was taken after 1330 calls. Twenty-two ECG abnormalities were recorded. In 63 patients receiving the beta-blocker carvedilol, the mean dosage increased from 36 to 42 mg. In the previous year there were 1.8 hospitalizations per patient, while in the follow-up period there were 0.2 hospitalizations per patient. Following up CHF patients using a nurse-led telecardiology programme seems to be feasible and useful.     

Immunohistochemical and molecular study of radiation-induced multiple meningiomas with pleural and pulmonary metastasis

In the present study, the telomerase activity and the putative alterations of genes involved in cell-cycle control (p53, Fas and pRb) were investigated in a radiation-induced meningioma with multiple recurrences and pleural-pulmonary metastases (the patient, a 34-year-old male, had a history of carcinoma of the tongue of testicular lymphocytic lymphoma). Expression of VEGF and vasculature pattern were also studied. Expression of VEGF, pRb and p53 were evaluated by immunohistochemistry on formalin-fixed, paraffin-embedded samples of the tumor. VEGFmRNA was determined by competitive PCR. Fas, FasL and hTERT were evaluated by RT-PCR. Telomerase activity was examined by the TRAP assay. An intense vascularization was observed, supported by high expression of VEGFmRNA (isoforms 121 and 165). pRb and p53 were overexpressed. Fas was undetectable with PCR, whereas FasL was positive. Furthermore, the lesion showed an elevated telomerase activity (TPG, 22), according to the high expression of hTERT. These findings emphasized that even among generally benign neoplasms, such as meningiomas, some highly malignant tumors may develop, as in our case, in which several mechanisms were activated in the cancer progression to guarantee the immortalization of cellular clones (angiogenic phenomenon, activation of telomerase and of anti-apoptotic mechanisms) and the blood spread. Thus, the data illustrate the importance of searching for genetic aberrations (which are a hallmark of malignancy) in meningiomas, as predictive and reliable factors of the possibility to recur and to metastasize.     

Insulin resistance and executive dysfunction in older persons

OBJECTIVES: To evaluate the association between insulin resistance (IR) and executive dysfunction in a large, population-based study of older persons without diabetes mellitus (DM) or dementia. DESIGN: Cross-sectional study. SETTING: Outpatient clinic in Greve in Chianti and Bagno a Ripoli, Italy. PARTICIPANTS: A total of 597 subjects aged 65 to 93 without DM or dementia. MEASUREMENTS: Anthropometric measurements; plasma fasting levels of glucose, insulin, cholesterol (total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol), and insulin-like growth factor-1 (IGF-1); homeostasis model assessment (HOMA) to estimate degree of IR; Trail Making Test (TMT) A; TMT-B; TMT-B minus TMT-A (DIFF B-A); and Mini-Mental State Examination (MMSE). RESULTS: IR (HOMA) was associated with longer TMT-B (correlation coefficient (r)=0.11; P=.006) and DIFF B-A times (r=0.10; P=.022). Subjects in the upper tertile of IR were older and had longer TMT-B and DIFF B-A than participants in the lowest tertile. After adjusting for age, sex, and years of formal education, IR was significantly correlated with TMT-A, TMT-B, and DIFF B-A. After adjusting for age, sex, education, body mass index, waist:hip girth ratio, HDL-C, triglycerides, IGF-1, hypertension, drug intake, and physical activity, the results did not significantly change. After introducing MMSE score into the model, IR continued to be an independent determinant of TMT-A (beta=11.005; P=.021), TMT-B (beta=28.379; P<.001), and DIFF B-A (beta=17.374; P=.011). CONCLUSION: IR is independently associated with frontal cortex function evidenced by poor TMT times in older persons without DM or dementia.     

Effect of different doses of progestin on uterine leiomyomas in postmenopausal women

OBJECTIVE(S): To evaluate the effects of two doses of medroxyprogesterone acetate (MPA) on uterine leiomyoma sizes and on uterine bleeding pattern in postmenopausal women treated with oral hormone replacement therapy (HRT). STUDY DESIGN: Thirty natural postmenopausal women affected by uterine leiomyomas were enrolled and treated with oral micronized estradiol (E(2)) at dose of 2 mg per day, and randomized to receive in association MPA at dose of 2.5 mg daily (group A) or of 5 mg daily (group B). At the beginning of the study and after 1 year of treatment, uterine leiomyomata dimensions were measured using transvaginal ultrasonography (TV-USG). The subjects were instructed to note on a daily dairy the number and severity of abnormal uterine bleeding (AUB) episodes. RESULTS: After 1 year of therapy, a significant changes in mean uterine leiomyomas size was observed in the group treated with higher dose of MPA. No significant differences in uterine bleeding were detected between the two groups. CONCLUSION(S): In postmenopausal women with uterine leiomyomas, it is necessary to use the minimal efficacious dose of progestin during HRT because of a higher risk to increase the tumors dimensions.     

Effect of estrogen replacement plus low-dose alendronate treatment on bone density in surgically postmenopausal women with osteoporosis

This prospective randomized, double-blind, placebo-controlled, clinical trial was performed to evaluate the effectiveness of estrogens plus low-dose alendronate on bone metabolism. A total of 150 surgically postmenopausal women with osteoporosis were randomized in three groups: group A, micronized E2 (2 mg/d) plus standard-dose alendronate (10 mg/d); group B, micronized E2 plus low-dose alendronate (5 mg/d); and group C, micronized E2 plus placebo (one tablet per day). In all women, bone mineral density (BMD) and serum bone metabolism markers were assessed at admission and every 6 months for 2 yr. After 2 yr, BMD significantly increased compared with baseline in all groups. The percentage BMD change was significantly higher in groups A and B than in group C. The differences in BMD detected between groups A and B were not statistically significant. Since the 6-month follow-up and throughout the study, serum osteocalcin and bone alkaline phosphatase levels and urinary deoxypyridinoline and pyrilinks-D excretion were significantly reduced in all groups. Serum bone alkaline phosphatase levels significantly decreased in groups A and B, without difference between them, in comparison with group C. In conclusion, in surgically postmenopausal osteoporotic women treated with estrogen replacement, the addition of alendronate at a low dose of 5 mg daily induces a gain of bone mass not significantly different in comparison with that obtained using a standard dose of 10 mg daily.     

Breath test as non-invasive assessment for the initial screening of non-ulcerous dyspepsia

Considering the important role of Helicobacter Pylori (Hp) in the most common gastro-intestinal pathologies, the Authors want to test the effectiveness of a non-invasive diagnostic technique for detection of the Hp in the gastric mucosa. At the end of experience they think, like the most of Literature, that the Breath Test, concerning sensibility and specificity, represent the gold standard for detection of the Hp.     

Late adverse reactions to intravascular iodinated contrast media

Late adverse reactions to intravascular iodinated contrast media are defined as reactions occurring 1 h to 1 week after contrast medium injection. They have received increasing interest over the past decade, but their prevalence remains uncertain and their pathophysiology is not fully understood. The Contrast Media Safety Committee of the European Society of Urogenital Radiology decided to review the literature and to issue guidelines. An extensive literature search was carried out and summarized in a report. Based on the available information, simple guidelines have been drawn up. The report and guidelines were discussed at the 8th European Symposium on Urogenital Radiology in Genoa. Late adverse reactions after intravascular iodinated contrast medium include symptoms such as nausea, vomiting, headache, itching, skin rash, musculoskeletal pain, and fever. A significant proportion of these reactions is unrelated to the contrast medium; however, allergy-like skin reactions are well-documented side effects of contrast media with an incidence of approximately 2%. Late reactions appear to be commoner after non-ionic dimers. The majority of late skin reactions after contrast medium exposure are probably T-cell-mediated allergic reactions. Patients at increased risk of late skin reactions are those with a history of previous contrast medium reaction and those on interleukin-2 treatment. Most skin reactions are self-limiting and resolve within a week. Management is symptomatic and similar to the management of other drug-induced skin reactions. Electronic Publication     

Structural requisites of 2-(p-chlorophenoxy)propionic acid analogues for activity on native rat skeletal muscle chloride conductance and on heterologously expressed CLC-1

(1) The 2-(p-chlorophenoxy)propionic acid (CPP) modulates in a stereoselective manner the macroscopic chloride conductance (gCl), the electrical parameter sustained by the CLC-1 channel, of skeletal muscle. In order to determine the structural requirements for modulating native gCl and to identify high-affinity ligands, the effects of newly synthesised CPP analogues have been evaluated on gCl of rat EDL muscle fibres by means of the two-microelectrode current-clamp technique. (2) Each type of the following independent modification of CPP structure led to a three- to 10-fold decrease or to a complete lack of gCl-blocking activity: replacement of the electron-attractive chlorine atom of the aromatic ring, substitution of the oxygen atom of the phenoxy group, modification at the chiral centre and substitution of the carboxylic function with a phosphonate one. (3) The analogues bearing a second chlorophenoxy group on the asymmetric carbon atom showed a significant gCl-blocking activity. Similar to racemate CPP, the analogue with this group, spaced by an alkyl chain formed by three methylenic groups, blocked gCl by 45% at 100 micro M. (4) These latter derivatives were tested on heterelogously expressed CLC-1 performing inside-out patch-clamp recordings to further define how interaction between drug and channel protein could take place. Depending on the exact chemical nature of modification, these derivatives strongly blocked CLC-1 with K(D) values at -140 mV ranging from about 4 to 180 micro M. (5) In conclusion, we identified four molecular determinants pivotal for the interaction with the binding site on muscle CLC-1 channels: (a) the carboxylic group that confers the optimal acidity and the negative charge; (b) the chlorophenoxy moiety that might interact with a hydrophobic pocket; (c) the chiral centre that allows the proper spatial disposition of the molecule; (d) an additional phenoxy group that remarkably stabilises the binding by interacting with a second hydrophobic pocket.