Exchange of unsaturated fatty acids between adipose tissue and atherosclerotic plaque studied with artificial neural networks.

The linoleic C18:2 (n-6) and linolenic C18:3 (n-3) are recognized as essential components of the diet. Free radical peroxidation of essential fatty acids (EFAs) present in lipoproteins produces oxidized low-density lipoproteins which play a critical role in the development of atherosclerosis. The accumulation of EFAs in the vascular wall and correlations between their content in the adipose tissue and atherosclerotic plaque have been confirmed. The present study was undertaken to determine the usefulness of a neural network for studying the exchange between tissues of linoleic, alpha-linolenic, and arachidonic acids-three fatty acids with a well-understood metabolism. Atheromatous plaques, adipose tissue, and serum were obtained from 31 patients who underwent surgery due to atherosclerotic stenosis of the abdominal aorta, iliac or femoral arteries. Fatty acids were extracted and separated as methyl esters using gas chromatography. Statistical analysis was done with STATISTICA neural networks package. Several correlations reported previously were corroborated and factors modifying the content of individual EFAs in adipose tissue and atherosclerotic plaque were revealed. Artificial neural networks (ANNs) were used to determine factors modifying the content of linoleic, alpha-linolenic, and arachidonic acids in human atheromatous plaques. The mechanism of exchange of some fatty acids between the adipose tissue, atheromatous plaque, and plasma is discussed. The results provide evidence for an effective mechanism of tissue uptake and turnover of linoleic acid. Reduced plasma levels of this acid are compensated by release from adipose tissue and atheromatous plaque. While alpha-linolenic acid is continuously taken up by the plaque, adipose tissue absorbs this acid to a certain level only. The dynamics of exchange of arachidonic acid between adipose tissue and atheromatous plaque reflects a minor role for adipose tissue in determining plaque content of this acid, suggesting that "de novo" synthesis is the chief source of arachidonic acid in plaques.

[Factors influencing the length of hospital stay of patients qualified for elective carotid endarterectomy]. / Czynniki wplywajace na dlugosc okresu hospitalizacji chorych kwalifikowanych do operacji udroznienia tetnic szyjnych.

The aim of this retrospective study was to identify the factors affecting long hospital stay of patients who underwent carotid endarterectomy. The analysis was based on 233 records of all patients operated on between 1995 and 1998. We have found that the main reasons of lengthened preoperative hospitalization were: insulin dependent diabetes and admission on the day excluding the chance of operation in a short time. Postoperatively, monitoring in intensive care unit and unfounded delay of discharge were the leading reasons of prolonged hospital stay.

Clinical presentation, diagnosis, and pharmacotherapy of patients with primary brain tumors.

OBJECTIVE: To briefly review the clinical presentation and diagnosis of patients with primary brain tumors, followed by an in-depth survey of the pertinent pharmacotherapy. DATA SOURCES: A detailed search of the neurologic, neurosurgical, and oncologic literature for basic science research, clinical studies, and review articles related to chemotherapy and pharmacotherapy of primary brain tumors. STUDY SELECTION: Relevant studies on tissue culture systems, animals, and humans examining the mechanisms of action, pharmacokinetics, clinical pharmacology, and treatment results of chemotherapeutic agents for primary brain tumors. In addition, studies of pharmacologic agents administered for supportive care and symptom control are reviewed. DATA SYNTHESIS: Primary brain tumors derive from cells within the intracranial cavity and generally present with headache, seizure activity, cognitive changes, and weakness. They are diagnosed most efficiently with magnetic resonance imaging. After diagnosis, the most common supportive medications include corticosteroids, gastric acid inhibitors, and anticonvulsants. Chemotherapy is adjunctive treatment for patients with malignant tumors and selected recurrent or progressive benign neoplasms. In general, the most effective chemotherapeutic drugs are alkylating agents such as the nitrosoureas, procarbazine, cisplatin, and carboplatin. Other agents used include cyclophosphamide, methotrexate, vincristine, and etoposide. Angiogenesis inhibitors and gene therapy comprise some of the novel therapeutic strategies under investigation. CONCLUSIONS: The efficacy of chemotherapy for primary brain tumors remains modest. Novel agents must be discovered that are more specific and attack tumor cells at the molecular level of tumorigenesis. Furthermore, strategies must be developed to counteract the pervasive problem of brain tumor chemoresistance.

Application of chemical immunomodulators to the treatment of cancer and AIDS.

A number of potential advantages, development of promising new agents, and the discovery of synergy with cytokines or cell products continue to spur research into the application of chemical immunomodulators for the treatment of cancer and AIDS. In preclinical in vitro and in vivo systems, chemical immunomodulators definitely modulate the immune system and have therapeutic efficacy. Although clinical trials have shown the ability of these agents to modulate the human immune system, thus far chemical immunomodulators have generally not fulfilled the therapeutic promise generated in animal models for the treatment of human diseases. While the discrepancy in results between animal models and human trials is obvious, the basis is not apparent. Species differences in elimination kinetics, presentation of active drug at the site of action, and the development of tachyphylaxis have been postulated as reasons for the minimal activity of these agents in humans. In addition, the use of investigational techniques established for cytotoxic agents may not be appropriate for immunomodulators. As with any immunomodulator, determining an optimal immunostimulatory dose and schedule and applying the therapy to patients with minimal tumor burden would perhaps be more appropriate than use of a maximally tolerated dose in patients with advanced disease. A dose-immunological effect relationship has recently been demonstrated for levamisole at doses higher than those used for many years in levamisole trials (99). While research and clinical investigation have identified several potentially useful chemical immunomodulators, the elementary understanding of the biochemical mechanisms involved in immunoregulation remains basic. Future research must elucidate these mechanisms, particularly in humans, to maximize the benefits of chemical immunomodulators as single agents or combined with cytotoxic chemotherapeutic agents, surgery, radiation therapy, other immunomodulators, and antiviral agents.

Prescription assistance programs: options for assisting the uninsured and underinsured.

The objectives of the study were to determine the prevalence of indigent patient or reimbursement assistance programs for prescription drugs sponsored by the pharmaceutical industry and to collect data describing them. A questionnaire was mailed to 121 manufacturers or marketers of prescription drugs selected from the 1990 edition of the Red Book and 1991 edition of the Physicians' Desk Reference. The availability of free drug to qualified indigent patients or the availability of experts to solve reimbursement issues was then ascertained. The general application procedures and features of both types of programs were documented. The authors found that indigent patient and reimbursement assistance programs are offered for many products by numerous pharmaceutical companies, although not always on a formal basis. Of the 69 (57%) companies responding to the survey, 46 (67%) offer indigent patient assistance programs and 31 (45%) offer reimbursement assistance programs. Application procedures and services provided vary considerably between companies. These findings suggest that the pharmaceutical industry is a potential source of assistance in procuring drugs for the indigent or underinsured patient populations and a resource for resolving insurance issues. It is essential to contact a sponsor to determine current program availability and application procedures. Further study is required to appraise the merit of such programs.