Supratentorial World Health Organization Grade 2 astrocytomas and oligoastrocytomas. A new pattern of prognostic factors

BACKGROUND: Prognostic factors for adult patients with supratentorial World Health Organization (WHO) Grade 2 astrocytomas and poorly defined. METHODS: The prognostic importance of pretreatment patient- and tumor-related factors was analyzed retrospectively in 197 adult patients with supratentorial astrocytomas (n = 153) or oligoastrocytomas (n = 44) using the multivariate Cox proportional hazards model. Endpoints were death and date of malignant transformation. All patients were treated similarly between 1979 and 1992 with iodine-125 implants as the primary treatment. RESULTS: A new prognostic pattern was detected. Unfavorable prognostic factors with regard to survival were 1) a tumor volume > or = 20 mL; 2) a performance status < or = 80; and 3) age > or = 40 years for the female subpopulation. Midline shift (another important tumor-related factor after univariate analysis) was highly correlated with tumor volume and therefore not included in the multivariate model. Risk factors of malignant transformation were 1) a tumor volume > or = 20 mL; 2) an enhancement in the computed tomography scan; and 3) age > or = 40 years for the female subpopulation. Prognostic factors created subsets of patients with 5-year survival rates ranging from as low as 5% to as high as 79%. CONCLUSIONS: Any treatment decision or evaluation of treatment efficacy should take into account the strong influence of both patient- and tumor-related factors. Any further study design should consider the detected interaction between gender and age and the importance of tumor volume.     

Placebo-controlled evaluation of Ritalin side effects

OBJECTIVE: To address the frequency of side effects of Ritalin therapy in children with attention deficit hyperactivity disorder (ADHD) using the Barkeley Side Effects Questionnaire (BSEQ) in a clinical setting. DESIGN: Randomized double-blind placebo-controlled cross-over trial. SETTING: A large rural tertiary care clinic. PATIENTS: 234 consecutive children aged 5 through 15 years who met the Diagnostic and Statistical Manual of Mental Disorders (3rd ed, revised) criteria for ADHD were enrolled. Of these children, 206 had sufficient side effects data for analysis. INTERVENTIONS: 0.3 mg/kg per dose and 0.5 mg/kg per dose Ritalin compared to placebo in separate 2-week trials. Each treatment was given three times a day for 7 consecutive days. MEASUREMENTS AND MAIN RESULTS: Parents, blinded to the treatment assignment, assessed side effects via the BSEQ at baseline and at the end of each of the 4 treatment weeks. Univariate odds ratios (OR) were used to describe the magnitude of differences in observed side effects between Ritalin and placebo weeks of the trial for each of the items on the BSEQ. The frequency of the following side effects significantly increased with Ritalin therapy: insomnia (OR = 3.13, 95% confidence interval [CI] = (1.80,5.42)), appetite disturbance (OR = 19.00, 95% CI = (9.18,39.31)), stomachache (OR = 7.00, 95% CI = (3.29, 14.89)), headache (OR = 5.29, 95% CI = (2.51,11.15)), and dizziness (OR = 7.50, 95% CI = (1.93,29.13)). The frequency of the following side effects significantly decreased with Ritalin therapy: staring and daydreaming (OR = 0.47, 95% CI = (0.27,0.84)), irritability (OR = 0.33, 95% CI = (0.18,0.61)), anxiety (OR = 0.42, 95% CI = (0.23,0.76)), and nailbiting (OR = 0.19, 95% CI = (0.07, 0.53)). The incidence rates of the remaining BSEQ items did not differ significantly between the Ritalin and placebo weeks of the trial. CONCLUSION: The BSEQ proved to be clinically effective in tracking Ritalin side effects and should be incorporated into the routine evaluation and monitoring of ADHD patients for whom stimulants are prescribed.     

The treatment of inclusion body myositis: a retrospective review and a randomized, prospective trial of immunosuppressive therapy

We have sought to examine the response to immunosuppressive therapeutic intervention in inclusion body myositis (IBM) in a retrospective review of prior responses to therapy and in an open, randomized crossover trial. We collected information on the response to prior therapy on 25 patients, and for prospective therapy on 11 of these patients. All met criteria for a definite idiopathic inflammatory myopathy and had biopsy-proven IBM. Clinical and laboratory results were assessed by interviews of patients and by chart review in the retrospective trial. Manual muscle strength was assessed by a single trained observer; the patients' activities of daily living were assessed by questionnaire; and serum tests of muscle-associated enzymes were measured in the prospective trial. In the retrospective review, prednisone appeared to have been of some, albeit modest, clinical benefit in 10 of 25 (40%) patients. Other therapies, primarily azathioprine and methotrexate, also appeared to have halted the progression of weakness in 8 of 35 trials (23%). In the prospective study, combination therapy of oral azathioprine and methotrexate and a biweekly infusion of high-dose intravenous methotrexate with leucovorin rescue were given for 3 to 6 months in an open, crossover design. Both the oral and the intravenous regimens were clinically effective in some patients. There was clinical improvement in 3 trials, stabilization in 11 trials, and worsening in 5 trials, out of a total of 19 completed (22 intended) trials. The presence of active inflammation at entry into the prospective therapeutic protocol, either directly observed on muscle biopsy or indirectly indicated by serum creatine kinase level, may have been associated with clinical improvement. A complete laboratory response with normalization of creatine kinase and other muscle-associated enzymes did not, however, significantly predict clinical responsiveness in the prospective trial. In this first report, to our knowledge, of a prospective trial of immunosuppressive therapy for this disease, stabilization and even slight improvement of strength and functional abilities appeared to be achieved in some patients. We believe that prednisone and other immunosuppressive therapies were of modest benefit in about half of patients with inclusion body myositis, especially those with some evidence of active inflammation. Stabilization of an otherwise inexorably deteriorating course appears, therefore, to be an attainable goal in some patients with IBM.     

Premenstrual syndrome

Premenstrual syndrome is a cyclical disorder involving behavioral, emotional, and physical symptoms during the premenstruum. Because of its unknown etiology, a variety of treatment options exist; yet no therapy has consistently reduced symptoms. Most recent advances have occurred in relaxation techniques and psychotropic therapies.     

Kinetics of circulating adhesion molecules and chemokines after mechanical trauma and burns

OBJECTIVE: To assess the role of circulating adhesion molecules and chemotactic cytokines within different settings of major trauma. DESIGN: Retrospective study. SETTING: Teaching hospitals, USA and Germany. SUBJECTS: Two groups of patients with multiple injuries (group I n = 155 and group II n = 12) with mean (SEM) injury severity scores (ISS) of 35 (4) and 32 (4) points, respectively, and 18 burned patients with a mean of ISS 38 (9) points. INTERVENTIONS: Serum samples were collected at the site of the accident and on admission to the (Group I) as well as during the post-trauma course in the hospital (Group II: days 1, 3, 5, 7, 10; Group III; weekly, up to week 10). MAIN OUTCOME MEASURES: Measurement of concentrations of soluble (s) adhesion molecules (sE-selectin, sP-selectin), and chemotactic cytokines (interleukin-8 [IL-8], epithelial cell derived neutrophil activating peptide 78 [ENA-78]) in serum after major mechanical trauma and burns. RESULTS: High concentrations of ENA-78 and sP-selectin were already present at the site of accident as well as one hour after injury. During recovery from the injuries, persistently high concentrations of IL-8, ENA-78, and sP-selectin were found, but sE-selectin was increased only during the first week after major trauma. CONCLUSION: Massive tissue trauma causes immediate activation of selected chemokines and adhesion molecules within minutes of the injury which will then persist depending on the type and severity of the injury for a substantial length of time. There was, however, no correlation between serum concentrations of the mediators investigated and susceptibility to complications or outcome.     

Injuries to research subjects A survey of investigators

A task force of the Department of Health, Education, and Welfare conducted a survey aimed at estimating the incidence of research-related injuries, with a view to determining the feasibility of compensating subjects injured during research. The data were obtained by telephone from 331 investigators conducting research on nearly 133,000 human subjects over the past three years. Eighty-five investigators reported at least one injury. Of the 4957 reported injuries, 3926 were classified as trivial, and 974 as temporarily disabling; of 57 injuries resulting in death or permanent disability, one disabling stroke, not clearly related to the research, occurred three days after a non-therapeutic procedure; the rest resulted from treatments expected to benefit the patients directly, usually cancer chemotherapy. The data suggest that the risks of participation in nontherapeutic research may be of no greater than those of everyday life, and in therapeutic research, no greater than those of treatment in other settings.