Binocular Interactions in the Lateral Suprasylvian Visual Area of Strabismic Cats Following Section of the Corpus Callosum

Visually responsive neurons have been recorded in the lateral suprasylvian area (LSA) of cats raised with either a convergent or a divergent strabismus. In contrast to areas 17 and 18, where many studies have documented a profound loss of binocularly activated neurons following early strabismus, in the LSA the majority of cells could still be binocularly driven. Acute or chronic section of the splenium of the corpus callosum reduced but did not abolish binocularity in the LSA. We propose that the widespread callosal connections, the large size of the receptive fields and the peculiar internal circuitry of the LSA all concur in permitting the maintenance of binocular coding in spite of early misalignment of the eyes.     

Different biological properties of paired HIV-1 isolates from peripheral blood mononuclear cells and cerebrospinal fluid.

Seven paired HIV-1 isolates from peripheral blood mononuclear cells (PMCs) and cerebrospinal fluid (CSF) of infected subjects at various stages of the disease were studied for their capacity to replicate in continuous cell lines (Molt-3 and U-937 cells) and to induce cytopathic effects "in vitro". Obtained results indicate that paired HIV-1 isolates from PMCs and CSF of the same patient can differ in their replicative activity "in vitro", suggesting that, at least in some cases, CSF isolates may represent a distinct subtype of HIV-1.     

Effects of sympathectomy on the in vivo α and β-responses of the parotid gland

Summary Salivary secretion in response to noradrenaline and isoprenaline was measured in innervated and chronically sympathectomized parotid glands of the rat. In innervated glands, the responses to isoprenaline lasted longer than those to noradrenaline. Chronic sympathetic denervation enhanced the responses to both noradrenaline and isoprenaline. The magnitude of the supersensitivity to isoprenaline was related to the dose and the time at which the responses were analyzed. Supersensitivity was greater for the initial than for the total secretion elicited by isoprenaline. Propranolol (1 mg/kg) and phenolamine (5 mg/kg) were used in order to determine the relative participation of and -adrenoceptors in the enhanced responses to isoprenaline. The results suggest that postjunctional supersensitivity for the secretory responses of this organ to isoprenaline is mainly mediated through -adrenoceptors of the secretory cells and -adrenoceptors of the myoepithelial cells.     

Trends in stomach carcinoma. A statistical analysis of 1204 cases

The authors report a retrospective analysis of their experience of gastric cancer. One thousand two hundred and four patients, observed between 1977 and 1994, of whom 1,094 underwent surgery, were studied. Data analysis was performed, dividing this period as follows: 1977-1982, 1983-1988, 1989-1994. The results reveal that, over time, substantial changes occurred both in tumor characteristics and surgical approach. With regards to tumor characteristics, the disease weighs heavily, even if it is less frequent than in the past (25% reduction), striking younger subjects and presenting in increasingly more aggressive forms [higher frequency of proximal (+11.4%) and diffuse forms (+18.1%), reduction of advanced forms (-11.6%) not proportional to the increase of early forms (+64.5%), as well as increase of cases with a short clinical history (+15.2%)]. In terms of surgical approach, while the use of conservative surgery was reduced during the study period, extensive procedures were more widely used, particularly in the curative treatment of advanced tumors (subtotal gastrectomies: reduction of 39.5%; total gastrectomies: increase of 106%). The increasing use of extended surgery is linked to the modifications occurred in tumor characteristics and in pre and post-operative management rather then to changes in surgical approach. It must be noted, however, that such technical advances have not yielded an improvement in survival (p = n.s.); as such, it is likely that gastric cancer has became a more aggressive disease and, therefore, has counterbalanced the benefits of early diagnosis and extended exeresis.     

Factors influencing outcome in gastric cancer involving muscularis and subserosal layer.

AIMS: The prognostic factors for advanced gastric carcinoma without serosal invasion (pT2 AGC) are not clear. In terms of prognosis, pT2 AGC is considered intermediate between early gastric cancer (EGC) and gastric carcinoma with serosal invasion. METHODS: From January 1985 to December 2000, 182 patients with pT2 AGC underwent curative gastric resection in our Department. Prognostic factors were evaluated by univariate and multivariate analyses. RESULTS: Univariate analysis demonstrated that gender, tumour location, lymph node involvement, Borrmann type, number of lymph nodes involved, venous infiltration and extent of lymphadenectomy were significantly related to the prognosis. Multivariate analysis revealed that extent of lymph node metastasis (N1 vs N0 relative risk (RR) of recurrences=3.96, p<0.05; N2 vs N0 RR=6.55, p<0.05), and extent of lymphadenectomy (D1 vs D2 RR=3.2, p<0.01) were independent prognostic factors. In a subset of patients in which venous infiltration was analysed, this factor was also significant (RR=3.9, p<0.05). CONCLUSIONS: Our study shows that lymph node involvement and venous infiltration are important prognostic factors for pT2 AGC and, as such, adjuvant chemotherapy could be useful in this group of patients. An extensive lymph node dissection, minimum D2, should always be performed in order to reduce the risk of recurrence.     

Dual Action of NAMI-A in inhibition of solid tumor metastasis: selective targeting of metastatic cells and binding to collagen.

NAMI-A is a ruthenium complex endowed with a selective effect on lung metastases of solid metastasizing tumors. The aim of this study is to provide evidence that NAMI-A's effect is based on the selective sensitivity of the metastasis cell, as compared with other tumor cells, and to show that lungs represent a privileged site for the antimetastatic effects. The transplantation of Lewis lung carcinoma cells, harvested from the primary tumor of mice treated with 35 mg/kg/day NAMI-A for six consecutive days, a dose active on metastases, shows no change in primary tumor take and growth but a significant reduction in formation of spontaneous lung metastases. Transmission electron microscopy examination of lungs and kidney shows NAMI-A to selectively bind collagen of the lung extracellular matrix and also type IV collagen of the basement membrane of kidney glomeruli. The half lifetime of NAMI-A elimination from the lungs is longer than for liver, kidney, and primary tumor. NAMI-A bound to collagen is active on tumor cells as shown in vitro by an invasion test, using a modified Boyden chamber and Matrigel, and it inhibits the matrix metallo-proteinases MMP-2 and MMP-9 at micromolar concentrations, as shown in vitro by a zimography test. These data show NAMI-A to significantly affect tumor cells with metastatic ability. Binding to collagen allows NAMI-A to exert its selective activity on metastatic cells during dissemination and particularly in the lungs. These data also stress the wide spectrum of daily doses and treatment schedules at which NAMI-A is active against metastases.     

Vascular endothelial growth factor and p53 expressions in liver and abdominal metastases from colon cancer.

OBJECTIVE: To determine the relationship between p53 overexpression and vascular endothelial growth factor (VEGF) upregulation in liver and abdominal metastases from colon cancer. The analysis in the two metastatic sites was carried out to evaluate the potential role of microenvironment in the molecular regulation of VEGF. METHODS: Bioptic specimens of liver and abdominal metastases from colon carcinomas were examined by immunohistochemistry for p53 and VEGF expressions. Consecutive cases with assessable tumor tissue were selected. RESULTS: The study population consisted of 24 cases having liver metastases and 34 cases having abdominal metastases. Abdominal metastases showed a higher number of VEGF-positive cases and a higher intensity of VEGF immunoreactivity than liver metastases did (p = 0.01). The combined analysis of p53 and VEGF showed a strong association between the two markers in the 24 liver metastases; 9 cases were VEGF positive/p53 positive and 15 cases were VEGF negative/p53 negative. This relationship was not found in the 34 abdominal metastases, which showed concordance between the two markers in 9 VEGF-positive/p53-positive cases only. CONCLUSIONS: Microenvironment factors like hypoxia may have a predominant role in inducing VEGF expression and they can override the molecular control of p53 on VEGF.     

Factors predicting radiation pneumonitis in lung cancer patients: a retrospective study.

PURPOSE: To evaluate clinical and lung dose-volume histogram based factors as predictors of radiation pneumonitis (RP) in lung cancer patients (PTs) treated with thoracic irradiation. METHODS AND MATERIALS: Records of all lung cancer PTs irradiated at our Institution between 1994 and 2000 were retrospectively reviewed. Eighty-four PTs with small or non-small-cell lung cancer, irradiated at >40 Gy, with full 3D dosimetry data and a follow-up time of >6 months from start of treatment, were analysed for RP. Pneumonitis was scored on the basis of SWOG toxicity criteria and was considered a complication when grade> or =II. The following clinical parameters were considered: gender, age, surgery, chemotherapy agents, presence of chronic obstructive pulmonary disease (COPD), performance status. Dosimetric factors including prescribed dose (Diso), presence of final conformal boost, mean lung dose (Dmean), % of lung receiving > or =20, 25, 30, 35, 40, and 45 Gy (respectively V20-->V45), and normal tissue complication probability (NTCP) values were analysed. DVHs data and NTCP values were collected for both lungs considered as a paired organ. Median and quartile values were taken as cut-off for statistical analysis. Factors that influenced RP were assessed by univariate (log-rank) and multivariate analyses (Cox hazard model). RESULTS: There were 14 PTs (16.6%) who had > or =grade II pulmonary toxicity. In the entire population, the univariate analysis revealed that many dosimetric parameters (Diso, V20, V30, V40, V45) were significantly associated with RP. No significant correlation was found between the incidence of RP and Dmean or NTCP values. Multivariate analysis revealed that the use of mitomycin (MMC) (P=0.005) and the presence of COPD (P=0.026) were the most important risk factor for RP. In the group without COPD (55 PTs, seven RP) a few dosimetric factors (Dmean, V20, V45) and NTCP values (all models) were associated with RP in the univariate analysis (P< or =0.06). According to the multivariate analysis, the use of MMC was independently associated with RP (P=0.007), while Dmean approached statistical significance (P=0.082). CONCLUSIONS: In this study the use of mitomycin or the presence of COPD is associated with a higher risk of RP. In the entire population NTCP values were not significantly correlated with the incidence of RP. Mean lung dose shows a clear trend toward statistical significance in the patient group without COPD.     

Value of P-glycoprotein and clinicopathologic factors as the basis for new treatment strategies in high-grade osteosarcoma of the extremities.

PURPOSE: To evaluate the prognostic value of P-glycoprotein and clinicopathologic parameters in a large series of high-grade osteosarcoma (OS) patients treated at the Rizzoli Institute. PATIENTS AND METHODS: With the use of immunohistochemistry, P-glycoprotein was assessed in 149 patients with primary, nonmetastatic, high-grade OS who were homogeneously treated with chemotherapy protocols based on doxorubicin, high-dose methotrexate, and cisplatin and the addition of ifosfamide in the postoperative phase. RESULTS: P-glycoprotein positivity was found in 47 of 149 cases (32%) and was significantly associated with a higher incidence of relapse and a worse outcome, as was age younger than 12 years and tumor volume greater then 150 mL at diagnosis. Multivariate analysis further confirmed the prognostic value of these parameters, which all were independent adverse prognostic factors. Event-free survival and proportional hazards regression analyses confirmed that overexpression of P-glycoprotein at clinical onset is the most important adverse prognostic factor for high-grade OS patients treated with these chemotherapy protocols. CONCLUSION: Increased P-glycoprotein levels, together with tumor volume and age, should be taken into consideration to identify, at time of diagnosis, subgroups of OS patients with a higher risk of recurrence. This subgroup identification will constitute the basis for drawing individualized treatment protocols on the basis of risk evaluation, with the aim of using more aggressive chemotherapy, or combination chemotherapy with other adjuvants, only in those patients for which more aggressive regimens are strictly necessary and warranted.