5-Fluorouracil and Recombinant Alpha Interferon-2a in the Treatment of Advanced Colorectal Carcinoma: a Dose Optimization Study

Summary

A dose optimization study was carried out with the aim of identifying the maximally tolerated dose of recombinant alpha interferon – 2a (raIFN-2a) in combination with 5-fluorouracil (5FU). 5FU was given at the dose of 750 mg/m² over a 4-hour infusion on day 1 – – > 5 followed by 750 mg/m² weekly i.v. bolus. Recombinant aIFN-2a was started at 3 × 10⁶ IU subcutaneously three times/week. 12 patients with advanced colorectal carcinoma were included in the study. 10 patients had previously received chemotherapy for advanced disease.

Severe fatigue, most likely attributable to rIFN, was the dose – limiting toxicity. The dosage of raIFN-2a could not be further escalated above 12 × 10₆ IU. At this dose level all patients required dose reduction due to fatigue, fever, myalgia and severe reduction of performance status.     

The problem of the aged person living alone: a methodological proposal for a pilot project of the aged person's and university student's cohabitation

The objective of the present study was to evaluate the outcome of a promotion program for the cohabitation between healthy living-alone-old person and university student. The study aimed to highlight the benefits of both the parts in terms of psyco-physical behaviour of the old subject and of logistic and financial support for the student. The survey was carried out between 1998 and 2000 on voluntary couples of old person-university student living in Padua. The study quantified the level of satisfaction of the material needs of the both parts and it also showed the affective relationship established between the old people and the young subjects.     

Cathepsin D in the malignant progression of neoplastic diseases (review).

Recent studies suggest that aspartic proteinase Cathepsin D may be implicated in the process of tumor invasion and metastasis. In fact several in vitro observations showed that this proteinase may facilitate the spread of neoplastic cells through different mechanisms related to its proteolytic activity, by acting at different levels of the metastatic cascade. Cathepsin D may promote tumor cell proliferation by acting as an autocrine mitogen through the activation of latent forms of growth factors or by interacting with growth factor receptors. The enzyme was also shown to be able to degrade in vitro extracellular matrix and to activate latent precursors forms of other proteinases involved in the invasive steps of the metastatic process. Although unequivocal proof of its active role in promoting these processes also in vivo has not been obtained so far, recent clinical observations which showed a positive correlation between levels of expression of Cathepsin D activity and malignant progression of some human neoplasms further support this hypothesis. These findings warrant extensive experimental and clinical studies to better assess the pathophysiological role of this acid proteinase in the spread of neoplastic diseases and suggest new and more selective therapeutic approaches to the treatment of human neoplasms.     

Acute myocardial effects of mitoxantrone in the rabbit

Some clinical studies that were performed for the purpose of assessing the potential cardiotoxicity of mitoxantrone (DHAD) have shown that repeated administrations of the drugs in some patients cause a mild impairment of cardiac functions and morphological changes in the myocardial cells qualitatively similar to those elicited by anthracyclines. Since doxorubicin has been reported to cause acute cardiac effects, probably related to its chronic cardiotoxicity, experiments were carried out on the rabbit heart to investigate whether DHAD is also able to induce acute cardiac effects. Our results show that this drug caused a reversible dose-related impairment of cardiac contractility on the isolated and perfused rabbit heart while it was not able to induce ECG alterations in normal rabbits. These findings demonstrate that in the rabbit DHAD induces an acute cardiac activity qualitatively similar to that of doxorubicin and suggest that this animal model could be a useful tool to study the cardiac actions and related pathogenetic mechanism(s) of this antitumor drug.     

A short-term infusion regimen of Cisplatin, 5-Fluorouracil and L-folinic Acid in advanced head and neck-carcinoma

Treatment of advanced head and neck cancer is still a matter of controversy. Although current chemotherapy regimens are able to induce high response rates, they have not shown improved survival. We employed a combination of cisplatin (CDDP), 5-fluorouracil (5FU) and 1-folinic acid (1-FA) in a 6-hour infusion schedule easy to administer on an outpatient basis. 49 patients have been included to date. The treatment plan consists of 5-FU (375 mg/m(2)) plus 1-FA (100 mg/m(2)) in a 4-hour i.v. infusion followed by a 2-hour i.v. administration of CDDP (20 mg/m(2)). This therapy was repeated for five consecutive days and recycled every 3-4 weeks. Out of 46 evaluable patients there were 6 complete responses (CR) and 23 partial responses (PR) for an overall response rate of 63%. Overall survival was 10.2 months (mean). Untreated patients had a higher probability of response as well as patients with naso-oropharyngeal primary tumor. Toxicity was generally mild with leukopenia, anemia and vomiting being the most frequent side effects. In conclusion, this combination appears well tolerated and active in the palliation of advanced head and neck cancer. However we think that increasing dose intensity of standard regimens and experimental new therapeutic approaches are needed to improve the clinical outcome of this disease.     

Predicting Concussion Recovery in Children and Adolescents in the Emergency Department

Purpose of Review

Concussion, or mild traumatic brain injury (mTBI), represents the majority of pediatric Emergency Department (ED) presentations of TBI. While most children and adolescents will recover within 4 weeks of injury, approximately one third will continue to experience persisting symptoms. This review aimed to provide an overview of literature from the past 5 years examining predictors of recovery in the ED.

Recent Findings

Predictors could be characterized into three categories; (i) cognition, (ii) proteomics, and (iii) pre-injury/injury-related factors. There is preliminary support for the use of computerized neuropsychological testing. The prognostic use of proteomics is a promising area of future research. Pre-injury and injury-related characteristics have been thoroughly examined and developed into a clinical risk score for predicting delayed recovery.

Summary

Substantial progress has been made in identifying risk factors for delayed recovery at ED presentation. The current evidence provides a platform for additional research that can refine and validate these predictors.