Modifying radical radiotherapy in high grade gliomas; shortening the treatment time through acceleration

PURPOSE: To evaluate the efficacy and toxicity of accelerated radiotherapy in patients with primary high grade glioma, where acceleration is used as a means of delivering a shortened course of radical radiotherapy. PATIENTS AND METHODS: Two-hundred and eleven patients with primary high grade glioma were treated at the Royal Marsden NHS Trust between 1987 and 1997 with accelerated radiotherapy (55 Gy in 34 fractions twice daily), to planning target volume (PTV) defined as enhancing tumour and a 3 cm margin. All had histologically confirmed high grade glioma (53 anaplastic astrocytoma, 137 glioblastoma multiforme, 4 gliosarcoma, 5 gemistocytic astrocytoma, 12 high grade astrocytoma not otherwise specified). The mean Karnofsky performance status (KPS) was 90 and median age was 54 years (range 19-77). RESULTS: Of 211 patients entered, 201 were able to complete radiotherapy; 39 patients (19%) had deterioration in KPS during radiotherapy and this was transient in 11. Median survival of 211 patients was 10 months with 1 year, 2 year, and 3 year survival probabilities of 38%, 14%, and 8% respectively. Age and extent of excision were independent prognostic factors for survival. Previous comparison to matched cohort receiving 60 Gy in 30 daily fractions did not demonstrate significant survival difference. CONCLUSION: Accelerated radiotherapy is a feasible treatment approach for patients with high grade glioma. The survival and functional outcome are comparable to conventional radiotherapy and the treatment is without serious acute toxicity. While acceleration of conventional dose irradiation could be tested in randomised studies, it is unlikely this approach would result in a clinically meaningful survival benefit. Accelerated radiotherapy therefore remains one of the ways of delivering radical irradiation in patients with high grade glioma. However, it adds complexity to what is a palliative treatment regimen and the rationale and advisability should be re-examined, particularly in terms of impact on quality of life, true patient preference, and health economic considerations.     

The place of premedication in pediatric practice

Behind the multiple arguments for and against the use of premedication, sedative drugs in children is a noble principle that of minimizing psychological trauma related to anesthesia and surgery. However, several confounding factors make it very difficult to reach didactic evidence-based conclusions. One of the key confounding issues is that the nature of expectations and responses for both parent and child vary greatly in different environments around the world. Studies applicable to one culture and to one hospital system (albeit multicultural) may not apply elsewhere. Moreover, the study of hospital-related distress begins at the start of the patient's journey and ends long after hospital discharge; it cannot be focused completely on just the moment of anesthetic induction. Taking an example from actual practice experience, the trauma caused by the actual giving of a premedication to a child who absolutely does not want it and may struggle may not be recorded in a study but could form a significant component of overall effect and later psychological pathology. Clearly, attitudes by health professionals and parents to the practice of routine pediatric premedication, vary considerably, often provoking strong opinions. In this pro–con article we highlight two very different approaches to premedication. It is hoped that this helps the reader to critically re-evaluate a practice, which was universal historically and now in many centers is more selective.     

Risperidone treatment of preschool children with thermal burns and acute stress disorder

Pharmacologic treatment of acute stress disorder (ASD) is a novel area of investigation across all age groups. Very few clinical drug trials have been reported in children and adolescents diagnosed with ASD. Most of the available, potentially relevant, data are from studies of adults with posttraumatic stress disorder (PTSD). The atypical antipsychotic agents have been reported to be effective as an adjunctive treatment for adults with PTSD. There have been a limited number of studies published regarding atypical antipsychotic treatment of PTSD in children and adolescents, and there is no current literature available on the use of these agents for children with ASD. This report describes the successful treatment of three preschool-aged children with serious thermal burns as a result of physical abuse or neglect. Each of these children was hospitalized in a tertiary-care children's hospital and was diagnosed with ASD. In all cases, risperidone provided rapid and sustained improvement across all symptom clusters of ASD at moderate dosages. Minimal to no adverse effects were reported. These cases present preliminary evidence for the potential use of risperidone in the treatment of ASD in childhood.     

Sexually dimorphic regions in the medial preoptic area and the bed nucleus of the stria terminalis of the guinea pig brain: a description and an investigation of their relationship to gonadal steroids in adulthood

Sexually dimorphic regions are described in two areas of the guinea pig brain: the medial preoptic area (MPOA) and the bed nucleus of the stria terminalis (BNST). The volume of a darkly staining portion of the MPOA is approximately 4-fold larger in male than in female guinea pigs, and the volume of a darkly staining portion of the BNST is approximately 36% larger in male than in female animals. The sex differences in both of these areas are present in animals that have been gonadectomized as adults as well as in intact animals, suggesting that they result from differences between the sexes in the hormonal environment during early development. Both the MPOA and the BNST bind high levels of gonadal steroids early in life, during the period when functional differentiation occurs. It is possible that dramatic morphological sex differences characterize such steroid-binding areas. Furthermore, these sexually dimorphic areas may form an anatomically and functionally interrelated system. Attention to these possibilities may help elucidate more precisely the neural basis for sexually dimorphic functions, as well as the basic mechanisms underlying sexual differentiation of behavior and the brain.     

Complications occurring in the postanesthesia care unit: a survey.

To identify and quantitate complications occurring in the postanesthesia care unit (PACU), a prospective study evaluated 18,473 consecutive patients entering a PACU at a university teaching hospital. Using a standardized collection form, the incidence of intraoperative and PACU complications was determined. The combined PACU and intraoperative complication rate was 26.7%. Data showed a PACU complication rate of 23.7%, with an overall intraoperative complication rate of 5.1%. Nausea and vomiting (9.8%), the need for upper airway support (6.9%), and hypotension requiring treatment (2.7%) were the most frequently encountered PACU complications. Patients in whom PACU complications developed were analyzed by ASA physical status. Of all patients experiencing nausea and vomiting (n = 1571), the highest percentage were ASA physical status II patients (n = 831). Likewise, in the group of 1450 patients who demonstrated a need for upper airway support, 792 were ASA physical status II. In patients experiencing a major cardiovascular complication, for example, variables associated with a greater risk of developing any PACU complications were ASA physical status (status II), duration of anesthesia (2-4 h), anesthetic technique, emergency procedures, and certain types of surgical procedures (orthopedic or abdominal). For patients admitted with a temperature of less than 35 degrees C the duration of the PACU stay was 152 +/- 46 min compared with 116 +/- 65 min for patients with a temperature greater than or equal to 36 degrees C (P less than 0.01). In conclusion, events occurring during the PACU period continue to be a source of patient morbidity.     

An appraisal of polystyrene-(ELISA) and nitrocellulose-based (ELIFA) enzyme immunoassay systems using monoclonal antibodies reactive toward antigenically distinct forms of human C-reactive protein

The purpose of this study was to compare and contrast two enzyme immunoassay systems: the enzyme-linked immunosorbent assay (ELISA), which utilizes polystyrene microtiter plates as the adsorptive surface and the enzyme-linked immunoflow assay (ELIFA), which utilizes nitrocellulose membranes. The principal parameter under scrutiny was the denaturing or unfolding effects caused by the interaction of the protein with the adsorptive surfaces in each assay system. These effects were monitored by utilizing two conformationally distinct forms of human C-reactive protein (CRP), the native form of CRP and a denatured form (M-CRP), with a corresponding panel of monoclonal antibodies (MAbs) specific to either CRP or M-CRP. The results show that the ELIFA system was less sensitive than the ELISA system but that the ELIFA assay can be completed in less time than the ELISA. Also, adsorption of native CRP to the polystyrene surface in the ELISA system resulted in conformational changes of the adsorbed native CRP protein such that M-CRP reactive determinants were available for binding with anti-M-CRP MAbs, whereas native CRP adsorbed to the nitrocellulose membrane in the ELIFA system resulted in very limited conversion of CRP to M-CRP reactive epitopes. These results have important implications for development of immunoassays and screening of MAbs for proteins whose conformations may be affected by adsorption to various surfaces.     

Giant Aneurysm of the Left Anterior Descending Coronary Artery in a Pediatric Patient with Behcet’s Disease

Behcet’s disease is a rare autoimmune vasculitis characterized by oral aphthosis, genital ulcers, and ocular and cutaneous lesions. Vascular involvement usually affects the veins more commonly than the arteries, and coronary arterial involvement is extremely rare. We report an adolescent with Behcet’s disease who developed a large pseudoaneurysm of the left anterior descending coronary artery requiring a coronary arterial bypass graft.     

Successful treatment of severe subcutaneous insulin resistance with inhaled insulin therapy

van Alfen‐van der Velden AAEM, Noordam C, de Galan BE, Hoorweg‐Nijman JJG, Voorhoeve PG, Westerlaken C. Successful treatment of severe subcutaneous insulin resistance with inhaled insulin therapy. The potential of inhaled insulin therapy for severe resistance to subcutaneous insulin was tested in a 7‐yr old boy with type 1 diabetes mellitus. The efficiency of 1 mg inhaled insulin (Exubera^®) was examined by a 4‐h euglycemic clamp study. During the clamp, the glucose infusion rate started to increase 25 min after inhalation and peaked 120 min after inhalation. Subsequently, a trial of inhaled insulin monotherapy was initiated consisting of pre‐meal inhalations and one inhalation during the night. Since glycemic control remained fair (HbA1c ～8.5%), this therapy was continued. Over the ensuing 18 months, mild keto‐acidosis occurred twice during gastro‐enteritis. Inhaled insulin was well tolerated and pulmonary function did not deteriorate. We conclude that severe resistance to subcutaneous insulin does not preclude sufficient absorption of insulin delivered by pulmonary.