Proton magnetic resonance spectroscopy in childhood brainstem lesions

Background Diagnosis of brainstem lesions in children based on magnetic resonance imaging alone is a challenging problem. Magnetic resonance spectroscopy (MRS) is a noninvasive technique for spatial characterization of biochemical markers in tissues and gives information regarding cell membrane proliferation, neuronal damage, and energy metabolism. Methods We measured the concentrations of biochemical markers in five children with brainstem lesions and evaluated their potential diagnostic significance. Images and spectra were acquired on a 1.5-T imager. The concentrations of N-acetylaspartate, tetramethylamines (e.g., choline), creatine, phosphocreatine, lactate, and lipids were measured within lesions located at the brainstem using Point-resolved spectroscopy sequences. Results Diagnosis based on localized proton spectroscopy included brainstem glioma, brainstem encephalitis, demyelination, dysmyelination secondary to neurofibromatosis type 1 (NF 1), and possible infection or radiation necrosis. In all but one patient, diagnosis was confirmed by biopsy or by clinical follow-up. Conclusions This small sample of patients suggests that MRS is important in the differential diagnosis between proliferative and nonproliferative lesions in patients without neurofibromatosis. Unfortunately, in cases of NF 1, MRS can have a rather misdiagnosis role.     

Evidence-based assessment of attention deficit hyperactivity disorder in children and adolescents.

This article examines evidence-based assessment practices for attention deficit hyperactivity disorder (ADHD). The nature, symptoms, associated features, and comorbidity of ADHD are briefly described, followed by a selective review of the literature on the reliability and validity of ADHD assessment methods. It is concluded that symptom rating scales based on the Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994), empirically and rationally derived ADHD rating scales, structured interviews, global impairment measures, and behavioral observations are evidence-based ADHD assessment methods. The most efficient assessment method is obtaining information through parent and teacher rating scales; both parent and teacher ratings are needed for clinical purposes. Brief, non-DSM based rating scales are highly correlated with DSM scales but are much more efficient and just as effective at diagnosing ADHD. No incremental validity or utility is conferred by structured interviews when parent and teacher ratings are utilized. Observational procedures are empirically valid but not practical for clinical use. However, individualized assessments of specific target behaviors approximate observations and have both validity and treatment utility. Measures of impairment that report functioning in key domains (peer, family, school) as well as globally have more treatment utility than nonspecific global measures of impairment. DSM diagnosis per se has not been demonstrated to have treatment utility, so the diagnostic phase of assessment should be completed with minimal time and expense so that resources can be focused on other aspects of assessment, particularly treatment planning. We argue that the main focus of assessment should be on target behavior selection, contextual factors, functional analyses, treatment planning, and outcome monitoring.     

Phosphorus Oxychloride in Organic Synthesis. Part 3: Synthesis of α-Benzoylaminocinnamic Acids

A new approach to the activation of reactants during the condensation of aromatic aldehydes with N-aroylglycines (acting as CH-acids) is described. The condensation reaction carried out on heating in phosphorus oxychloride leads to a high yield of 4-benzylideneoxazol-5-one derivatives. The hydrolysis of these intermediate products yields the target α-benzoylaminocinnamic acids. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 7, pp. 41 – 42, July, 2005.     

How Should Functionally Equivalent Drugs be Reimbursed?

Statutory reimbursement agencies as well as private insurers throughout member states of the Organization for Economic Cooperation and Development (OECD) reimburse the cost of medicines on the basis of criteria that include robust clinical evidence, budget impact analysis, and incremental cost effectiveness. The Centers for Medicare and Medicaid Services (CMS) in the US are no exception to this rule and are, in principle, seeking to maximize benefit for their Medicare enrollees, whilst ensuring reasonable drug outlays for the small number of drugs that they reimburse. This paper provides a retrospective analysis of the way two functionally equivalent drugs are treated for reimbursement purposes by the CMS; the period under consideration was 2001–3. The two drugs, epoetin-α and darbepoetin-α, are used for the treatment of anemia in renal failure and in patients receiving chemotherapy. By reviewing the publicly available pharmacological and clinical data of epoetin-α and darbepoetin-α, the paper confirms the two drugs’ functional equivalence, despite their structural differences. The implications of dose conversion ratios and costs to Medicare are subsequently explored. It is argued that the issue of dose equivalence between epoetin-α and darbepoetin-α has significant implications for patients, practitioners, and payors. A payor’s perspective is adopted in this respect, whereby clinical evidence and pricing data are used simultaneously. Based on the clinical evidence, a dose conversion ratio for epoetin-α:darbepoetin-α is established, which achieves a comparable clinical effect for the two drugs and this is set to be <254IU:1μg. The incremental costs to Medicare are calculated subsequently. The Average Wholesale Price and the Outpatient Prospective Payment System rule that Medicare uses to reimburse providers are used and suggest that treatment of cancer patients with chemotherapy-related anemia with epoetin-α would save Medicare an estimated $US600 million each year. Patients would also benefit significantly in terms of lower co-payments for epoetin-α. The evidence is supportive of the decision made by the CMS to reimburse the two drugs at the rate reflecting the achievement of comparable clinical effects and therefore reducing the pass-through payments for darbepoetin-α to zero for the 2002–3 fiscal year.     

Steroids in Duchenne muscular dystrophy--deflazacort trial

We conducted a double blind controlled trial in 28 Duchenne muscular dystrophy (DMD) patients with Deflazacort (DF), an oxazoline derivative of prednisolone which reduces its side-effects. Myometric muscle strength measurements, Scott Score and timed tests showed statistically significant improvement for the treated group (P less than 0.05). Side-effects after 9 months of treatment included mild cushingoid appearance in four patients (28%) and moderate in only one (7%), increased appetite in seven (50%), increased body hair in four (28%), irritability and hyperactivity in three (21%). Increased body weight was not prominent and was controlled with dietary measures. No patient had to be withdrawn from medication. More research and long-term follow-up are needed in order to establish the mechanism of improvement and the consequences of long-term steroid administration in DMD. In this regard DF appears as an alternative to prednisone preserving its benefits but with fewer side-effects.     

Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy.

We examined binding to excitatory amino acid and inhibitory amino acid receptors in frozen hippocampal sections prepared from surgical specimens resected from 8 individuals with medically refractory temporal lobe epilepsy. The excitatory receptors studied included N-methyl-D-aspartate (NMDA), strychnine-insensitive glycine, phencyclidine, and quisqualate. The inhibitory receptors studied were gamma-aminobutyric acid type A (GABAA) and benzodiazepine. Excitatory and inhibitory amino acid receptor binding were differentially altered in the patients with temporal lobe epilepsy in comparison to 8 age-comparable autopsy control subjects, and changes in receptor binding were regionally selective in four areas. Binding to phencyclidine receptors associated with the NMDA channel was reduced by 35 to 70% in all regions in the hippocampi of the patients. In contrast, binding to the NMDA recognition site and its associated glycine modulatory site was elevated by 20 to 110% in the cornu ammonis (CA) 1 area and dentate gyrus of the hippocampus of the patients. Binding to these sites was unaffected in area CA4. Binding to the quisqualate-type excitatory amino acid receptor was unchanged in all regions except the stratum lacunosum moleculare CA1, where it was increased by 63%. GABAA and benzodiazepine receptor binding was reduced by 20 to 60% in CA1 and CA4, but unchanged in dentate gyrus. The data indicate that excitatory and inhibitory amino acid receptors are altered in the hippocampus of patients with temporal lobe epilepsy.     

Chronic oral treatment with diltiazem or verapamil decreases isolation-induced activity impairment in elevated plus maze

Adult male Wistar rats were either socially isolated or group-housed for 6 weeks and then tested in an elevated plus maze. During isolation the rats received either water or two concentrations of the calcium channel inhibitors, diltiazem or verapamil, in drinking solutions (approximately 5 and 10 mg/kg daily). Isolated rats showed a significantly lower total number of arm entries, a lower percentage of open arm entries and negligible time spent therein than did group-housed animals. Verapamil, in the higher dose, prevented that effect of isolation. Treatment with diltiazem brought about a similar tendency, though the effect did not reach statistical significance. Chronic treatment of group-housed rats with either drug failed to influence their behavior in the plus maze. We conclude that certain calcium channel inhibitors may decrease the behavioral deficit in the elevated plus maze that follows chronic social isolation.     

Involving patients in do not resuscitate (DNR) decisions: an old issue raising its ugly head.

A recent paper in this journal (1) suggests that involving terminally ill patients in choices concerned with Cardio-Pulmonary Resuscitation (CPR) produces 'psychological pain' and therefore is ill-advised. Such a claim rests on anecdotal observations made by the authors. In this paper I suggest that drawing conclusions in ethics, no less than in science, requires a rigorous framework and cannot be relegated to personal observation of a few cases. The paper concludes by suggesting that patients, if we acknowledge their valid interest in making their own choices, must themselves be allowed to make a prior choice about choosing. Those who may not wish to choose may properly be relieved of this burden and may allow another to choose for them. Routinely allowing others to make choices for competent adults, however, is likely to decrease communication with the dying patient and to introduce an atmosphere of suspicion and fear and to exclude the competent patient from his/her rightful place in the community.