Selective occlusion of tumor blood vessels by targeted delivery of an antibody-photosensitizer conjugate

The irregular vasculature and high interstitial pressure of solid tumors hinder the delivery of cytotoxic agents to cancer cells. As a consequence, the doses of chemotherapy necessary to achieve complete tumor eradication are associated with unacceptably high toxicities. The selective thrombosis of tumor blood vessels has been postulated as an alternative avenue for combating cancer, depriving tumors of nutrients and oxygen and causing an avalanche of tumor cell deaths. The human antibody L19, specific to the EDB domain of fibronectin, a marker of angiogenesis, is capable of selective in vivo localization around tumor blood vessels and is thus a suitable agent for delivering toxic payloads to the tumor neovasculature. Here we show that a chemical conjugate of the L19 antibody with the photosensitizer bis(triethanolamine)Sn(IV) chlorin e(6), after intravenous injection and irradiation with red light, caused an arrest of tumor growth in mice with subcutaneous tumors. By contrast, a photosensitizer conjugate obtained with an antibody of identical pharmacokinetic properties but irrelevant specificity did not exhibit a significant therapeutic effect. These results confirm that vascular targeting strategies, aimed at the selective occlusion/disruption of tumor blood vessels, have a significant anticancer therapeutic potential and encourage the use of antibody-photosensitizer conjugates for the therapy of superficial tumors and possibly other angiogenesis-related pathologies.     

Survival rates and tolerability of platinum-based chemotherapy regimens for elderly patients with non-small-cell lung cancer (NSCLC)

BACKGROUND: The combination therapy for non-small-cell lung cancer (NSCLC) with platinum-based treatment is well known, but its utility in elderly has not been explored systematically. AIM: To examine whether aging compromises survival or exacerbates toxicity in patients with advanced lung cancer receiving platinum-based treatment. METHODS: We performed a nested case-control study in a cohort of chemotherapy na?ve patients enrolled January 1998-December 2003. Cases were consecutive patients over 70 at diagnosis with stage III or IV NSCLC. Controls were a subset of patients under 70 years matched by stage and year in which they had been treated. All patients received Cisplatin (80 mg/m2) or Carboplatin (4-6 AUC), every 4 weeks, followed by Vinorelbine (30 mg/m2) for a maximum of six courses. The medical history, physical examination and tumor imaging evaluation were performed at baseline and then monthly. Survival was calculated by Kaplan-Meier method and log-rank test was used for survival comparisons. Chi-squared test was used to compare side effects in the two groups. RESULTS: A total of 419 patients were identified for the case-control study (205 elderly/214 young) with 3.6 cycles per patient, on average. The 2- and 3-year survival rates were 20.5% and 6.8% for elderly patients and 9.8% and 2.3% for younger patients (p=0.017 and 0.014, respectively for 2 and 3 years). The proportion of patients with adverse effects, either grade 3 or 4, was the same in both groups at 2 years (43.9% versus 43.9%; p=0.99). CONCLUSIONS: Although elderly patients may self-select or be selected to be healthier, our findings suggest that elderly patients currently undergoing chemotherapy for lung cancer do as well or better than younger patients. Elderly age alone should not preclude patients from receiving platinum-based chemotherapy, since it seems well tolerated and effective in non-small-cell lung cancer among elderly patients.     

Socioeconomic disadvantage and periodontal disease: the Dental Atherosclerosis Risk in Communities study

OBJECTIVES: We used data from the Dental Atherosclerosis Risk in Communities study to examine whether individual- and neighborhood-level socioeconomic characteristics were associated with periodontal disease. METHODS: We assessed severe periodontitis with a combination of clinical attachment loss and pocket depth measures. Marginal logistic regression modeling was used to estimate the association between individual and neighborhood socioeconomic indicators and prevalence of severe periodontitis before and after control for selected covariates. Residual intraneighborhood correlations in outcomes were taken into account in the analyses. RESULTS: Individual-level income and education were associated with severe periodontitis among Whites and African Americans, and these associations remained significant after adjustment for age, gender, recruitment center, and neighborhood socioeconomic score. Low-income Whites residing in disadvantaged neighborhoods had 1.8-fold (95% confidence interval=1.2, 2.7) higher odds of having severe periodontitis than high-income Whites residing in advantaged neighborhoods. CONCLUSIONS: Individual income and education were associated with severe periodontitis independently of neighborhood socioeconomic circumstances. Although the association between neighborhood socioeconomic status and severe periodontitis was not statistically significant, poverty and residence in a disadvantaged neighborhood were associated with higher odds of severe periodontitis among Whites.     

A continuous dietary supply of free calcium formate negatively affects the parietal cell population and gastric RNA expression for H+/K+-ATPase in weaning pigs

Baby formula acidification can be used to reduce diarrhea. Calcium formate is a dietary acidifier frequently used in animal weaning diets; it is also a source of available calcium. Gastric acidification reduces gastrin release and hydrochloric acid (HCl) secretion. To study the medium-term effects on fundic gastric mucosa, we fed weaning pigs control diets or diets supplemented with free or fat-protected calcium formate. We evaluated the following: 1) the number of HCl-secreting parietal cells, by immunohistochemistry using an antibody against H(+)/K(+)-ATPase; 2) the number of enteroendocrine cells immunohistochemically stained with chromogranin A (CGA), somatostatin, and histamine (HIS); and 3) the expression of the H(+)/K(+)-ATPase gene, by real-time RT-PCR in the oxyntic mucosa. Cells co-staining for CGA and HIS were defined as enterochromaffin-like (ECL) cells. Pigs fed calcium formate had fewer parietal cells and a lower expression of the H(+)/K(+)-ATPase gene than the controls (P < 0.05). This reduction did not occur in pigs fed fat-protected calcium formate. Somatostatin immune-reactive cells were also more numerous in pigs fed free calcium formate than in controls (P < 0.05). The number of ECL cells was not affected. Using covariance analysis, the number of parietal cells explained part of the differences in the expression of H(+)/K(+)-ATPase gene (positive correlation, r = 0.385, P < 0.01), and excluded the statistical significance of the diet. In the future, the effects on the oxyntic mucosa should be checked when the diet supplemented with calcium formate is discontinued. Furthermore, a reduction in the number of parietal cells could impair the absorption of vitamin B-12 due to a reduced secretion of the intrinsic factor by these cells.     

Attention and physical presence: expressive dimensions and the dialogical practice of nursing care according to the perpective of the hospitalized client

Qualitative study, discusses the attention and the physical presence as the fundamental care in the dialogical relation between the client living with AIDS and the hospital nursing, using concepts of expressive activities and human care, according to Watson and dialogue, according to Freire. Five persons participated with internment experience, under ambulatory follow up in a hospital of Rio de Janeiro city. It used the triangulation techniques: almanac, semi-structured interview and participant observation. It showed the importance of the valorization of that is necessary and of interest of the client from the attention and the physical presence as essential requirements in the human care, expressed in the dialogical experience and in the participation of the client in the whole care process.     

Comparative evaluation of the effects of unilateral lesion versus electrical stimulation of the globus pallidus internus in advanced Parkinson's disease

OBJECTIVE: To perform a prospective analysis on the effects of unilateral lesion versus unilateral electrical stimulation (ES) of the globus pallidus internus (Gpi) in the treatment of bilateral Parkinson's disease (PD). MATERIALS AND METHODS: We studied 18 patients with stages III-V on the Hoehn and Yahr (H-Y) scale having prominent rigidity, bradykinesia and gait disturbances. Nine patients were treated with lesions and 9 patients with ES. Both groups were evaluated using the New York Parkinson's Disease Scale, the Unified Parkinson's Disease Rating Scale part III, and the H-Y scale and with specific items of tremor, rigidity and bradykinesia independently on each side. Both lesions and electrodes for ES were placed stereotactically in the Gpi as confirmed by postoperative magnetic resonance images. Significance of changes was evaluated with the Wilcoxon test after 3 and 6 months. Significance of intergroup differences was evaluated using the Mann-Whitney U test. RESULTS: Lesions and ES significantly decreased rigidity (p < 0.01) and bradykinesia (p < 0.005) in the contralateral extremities. ES significantly decreased tremor in the contralateral extremities (p < 0.01) and rigidity and bradykinesia ipsilaterally (p < 0.01) at 3 months. There were no significant intergroup differences. The H-Y scale score showed improvement in self-sufficiency. L-DOPA dose was decreased by 31%. CONCLUSIONS: ES was a safer procedure and more efficient in controlling PD symptoms. Unilateral lesions and ES may improve bilateral symptoms to the point of making patients self-sufficient.