Pharmacokinetics and pharmacodynamics of anticancer agents: contributions to the therapy of childhood cancer

Strategies for treating pediatric malignancies have not only been successful (i.e., curative) for several disseminated childhood cancers, they have also served as paradigms for the therapy of many adult cancers. Initial strategies included combined treatment modalities (chemotherapy, surgery, radiotherapy) and combinations of different pharmacologic classes of anticancer drugs given in the appropriate schedules. Despite the currently successful therapy for some malignancies (e.g., 70% 4-year disease-free survival in acute lymphocytic leukemia), many children die without known reason. Recent advances in the clinical pharmacology of anticancer drugs have identified relationships between dose intensity and response (efficacy, toxicity). Traditional methods of measuring dose intensity (prescribed dose) have evolved to more sophisticated approaches in maximizing the intensity of treatment, with good response rates. Other methods of optimizing chemotherapy for individual patients include bone marrow support procedures and therapy with biologic response modifiers. Relatively few clinically useful new anticancer drugs have been discovered in the past several years. Fortunately, the potential to improve therapy with currently available agents has come about through enhanced knowledge of the biochemical and clinical pharmacology of anticancer drugs and biologic response modifiers, as well as improved understanding drug resistance biology.     

Titration of duration discrimination in behavioral pharmacology and toxicology

This study investigated a discrete-trial, titration duration discrimination procedure in behavioral pharmacology. Pentobarbital and d-amphetamine, measured with this procedure, selectively affected discrimination more than response tendencies. Pentobarbital also tended to affect selectively discrimination of longer durations, whereas d-amphetamine did not. Further experiments showed that (1) other algorithms for modulating stimulus duration are useful in behavioral pharmacology and toxicology, (2) threshold estimates are similar with the method of constant stimuli and the method of titration, and (3) this titration procedure permits the separate examination of drug effects upon discrimination and upon response tendencies; the fixed-interval procedure does not. Baseline variability was an important correlate of drug effects in that the endpoints with more variable baselines were also more sensitive to drugs.     

Nutritional issues in pediatric inflammatory bowel disease.

Malnutrition, characterized by weight loss, growth failure and micronutrient depletion, are prominent features of inflammatory bowel disease (IBD) in the pediatric age group. Accurate evaluation of the patient's nutritional status and appropriate nutritional support, whether enteral or parenteral, constitute integral parts of the management of the growing child with IBD. Over the past two decades, a number of studies have supported the potential use of nutritional therapy to induce remission and to control disease activity in symptomatic Crohn's disease. More recently, preliminary studies on the use of dietary supplements of marine-oil-derived omega-3 fatty acids have also indicated a beneficial effect in IBD patients. In parallel with these clinical trials, scientific research has recently focused on the concept that specific dietary alterations can modulate the immune response. Components of the diet that may have particular relevance to mucosal immunity and the pathogenesis of IBD include polyunsaturated fatty acids, nucleotides, and amino acids such as glutamine and arginine. Future research in the interactions between specific nutrients and the immune system will likely increase our understanding of the causes of IBD, as well as enhance the development of novel nutritional therapies for IBD patients.     

How negative are we to the idea of suicide prevention?

Assessment of attitudes amongst health care professionals to suicide prevention reveals a considerable degree of doubt with regards to its feasibility and appropriateness. The various professional groups may vary considerably in the degree of negative attitudes which they exhibit. Such findings suggest that there is an urgent need to ensure that health care professionals are fully informed about the key facts concerning suicide and preventive strategies. Key elements of clinical practice and service organization with regards to suicide prevention are discussed.     

Biliary infusion therapy in the inspissated bile syndrome of cystic fibrosis

A 3.5-month-old white boy was born with meconium ileus, peritonitis, and jejunal atresia from cystic fibrosis. He subsequently developed unrelenting and severe extrahepatic biliary obstruction as demonstrated by liver biopsy showing periportal inflammation, cholestasis, and fibrosis. Surgical exploration confirmed the diagnosis of extrahepatic biliary obstruction by severely inspissated bile. A cholecystostomy tube was left in place. The cholestasis remained unresponsive to conservative medical therapy. The obstruction was relieved by hydrostatic infusion of 2% N-acetylcysteine into the biliary tree over a 6-day period. The child also received concurrently four i.v. injections of synthetic cholecystokinin. This therapeutic modality was thought to be both safe and effective.     

The zygomatico-temporal approach to the skull base: a critical review of 11 patients.

The zygomatico-temporal approach to the base of the skull is a relatively new but established surgical technique. The approach involves the removal of the zygomatic bone to provide access to the skull base, middle cranial fossa, parasellar region and interpeduncular cistern with minimal brain retraction. An excellent view of the bifurcation of the basilar artery and suprasellar region is provided. The outcome of 11 patients undergoing this procedure is reported with particular reference to the post-operative morbidity and the cosmetic result.     

Examination of pre- and posttreatment MHPG during cognitive therapy.

Sixteen unipolar depressed patients were treated with cognitive therapy for 12 weeks. Pretreatment 24-hour urinary MHPG levels were unable to predict treatment response. There was a nonsignificant trend for cognitive therapy responders to show a decrease in MHPG during treatment when compared to nonresponders.