Minimal important differences in the Migraine-Specific Quality of Life Questionnaire (MSQ) version 2.1

To propose minimal important differences (MID) for the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v2.1). To our knowledge (to date), no published MID values exist for the MSQ v2.1 in any population. Analyses were performed on data from two pivotal clinical trials of topiramate for migraine prevention ( n  = 916), as well as from the QualityMetric National Headache Survey ( n  = 1016). Analyses included both distribution- and anchor-based MID techniques as well as group- and individual-level MID values. Group-level anchor-based MID values ranged from 3.2 [Role Restrictive domain (RR)] to 7.5 [Emotional Functioning domain (EF)], setting the minimum level of appropriate MID (which can also aid with power analysis). Individual-level distribution-based MID values resulted in highly similar estimates from two large databases: median MID of 8.5 for RR, 9.2 for Role Preventive (RP) and 12.0 for EF. Finally, individual-level anchor-based MID values ranged from 5.0 (RR and RP domains) to 10.6 (EF). For group-level purposes of calculating power for future studies, an MID of 3.2, 4.6 and 7.5 for RR, RP and EF is recommended. For within-group analyses for analysing clinical trial efficacy of each patient's change with responder analyses, 5 points is necessary for RR. For RP and EF, ranges are recommended: 5.0 to 7.9 for RP and 8.0 to 10.6 for EF. These latter two domains tend to have more error in the MID, and thus a sensitivity analysis with both ends of the range should be used to confirm significant differences in responder analyses.     

Is phenytoin contraindicated in patients receiving cranial irradiation ?

Three recent publications have reported the development of erythema multiforme and Stevens-Johnson syndrome in patients receiving cranial irradiation and sodium phenytoin. Some authors have recommended that patients receiving whole brain radiation therapy and who have had seizures should not be prescribed phenytoin but an alternative anticonvulsant. This article reviews the current literature pertaining to the development of this potentially lethal complication in patients receiving whole brain radiation and phenytoin, with reference to the single recorded case of Stevens-Johnson syndrome in a patient receiving cranial irradiation and phenytoin in Auckland, New Zealand. While the clinical picture in the 16 patients reported in the literature and the current case report differed from the classical form of erythema multiforme, a similar pattern of presentation and outcome appeared in all patients reviewed, suggesting that the combination of phenytoin, cranial irradiation and the gradual reduction of concomitant steroids seem to lead to the development of erythema multiforme and/or Stevens-Johnson syndrome. The data presented, although sparse, suggest that phenytoin should not be prescribed in patients receiving cranial irradiation.     

Assessing the validity of body mass index standards in early postmenopausal women

OBJECTIVE: To examine the relationship between percentage of total body fat (%Fat) and body mass index (BMI) in early postmenopausal women and to evaluate the validity of the BMI standards for obesity established by the NIH. RESEARCH METHODS AND PROCEDURES: Three hundred seventeen healthy, sedentary, postmenopausal women (ages, 40 to 66 years; BMI, 18 to 35 kg/m(2); 3 to 10 years postmenopausal) participated in the study. Height, weight, BMI, and %Fat, as assessed by DXA, were measured. Receiver operating characteristic analysis was performed to evaluate the ability of BMI to discriminate obesity from non-obesity using 38%Fat as the criterion value. RESULTS: A moderately high relationship was observed between BMI and %Fat (r = 0.81; y = 1.41x + 2.65) with a SE of estimate of 3.9%. Eighty-one percent of other studies examined fell within 1 SE of estimate as derived from our study. Receiver operating characteristic analysis showed that BMI is a good diagnostic test for obesity. The cutoff for BMI corresponding to the criterion value of 38%Fat that maximized the sum of the sensitivity and specificity was 24.9 kg/m(2). The true-positive (sensitivity) and false-positive (1--specificity) rates were 84.4% and 14.6%, respectively. The area under the curve estimate for BMI was 0.914. DISCUSSION: There is a strong association between %Fat and BMI in postmenopausal women. Current NIH BMI-based classifications for obesity may be misleading based on currently proposed %Fat standards. BMI >25 kg/m(2) rather than BMI >30 kg/m(2) may be superior for diagnosing obesity in postmenopausal women.     

Preliminary study of the behavioral effects of LBS-neuron implantation on seizure susceptibility following middle cerebral artery occlusion in the rat

Neural transplantation is a promising treatment strategy that can restore the motor, sensory and cognitive functions in the rat middle cerebral artery occlusion (MCAO) model of stroke. In particular, neuronal cells derived from a human teratocarcinoma cell line, called hNT neurons or LBS neurons (clinical grade preparation), are effective in improving behavioral recovery after stroke. In the elderly, epilepsy is a common sequelae of stroke, especially if the infarction involves cerebral cortex. However, the effect of implanting neural cells on seizure susceptibility in the MCAO model has not yet been determined. The purpose of this study was to determine the susceptibility to pentylenetetrazol (PTZ)-induced seizures in normal, MCAO-lesioned and MCAO-lesioned rats in which the LBS neurons were injected. Adult, male Sprague-Dawley rats were subjected to 60 min of MCAO using the intraluminal filament technique followed 3–4 weeks later by transplantation of 80,000 LBS-neurons into the ipsilateral cortex. Susceptibility to PTZ-induced seizures was tested 4–6 weeks post-transplant at doses of 35, 50 and 70 mg/kg, administered subcutaneously. Latency to the first ictal response, latency to first generalized seizure, duration of the first generalized seizure, and the number of generalized seizures in an hour post-PTZ treatment observation period was determined. Even though there was a tendency for groups that underwent MCAO to be more susceptible to seizures, there were no statistically significant differences between the groups and no differences between MCAO alone and MCAO animals in which cells had been implanted. While grafted cells were identified in all but one injected animal, the results suggest that the grafts may not have been healthy either from immunological rejection or PTZ-induced injury. These results suggest that while placing cells within the cortex does not reduce seizure susceptibility, it also does not increase the incidence of seizures. Further investigations are warranted.     

Cytogenetic and molecular genetic analysis of tumorigenic human bronchial epithelial cells induced by radon alpha particles

To establish a cell culture model for lung carcinogenesis, independent populations of the human papillomavirus 18-immortalized human bronchial epithelial cell line BEP2D were treated with high linear energy transfer radon-simulated alpha-particles, expanded and xenotransplanted into Nu/Nu mice. Six independent cell lines were established from tumors that developed from three separate radiation treatments as follows: treatment (Tx) 1 (30 cGy--two doses), H2BT, Tx 2 (30 cGy-- single dose), R30T1L, R30T2 and R30T3L, Tx 3 (30 cGy--single dose), H1ATN and H1ATBA1. Cytogenetic analysis revealed common changes in all tumor lines: loss of the Y chromosome (ch), one of three copies of ch8, one of three copies of ch14, and one of two copies of ch4p16-pter and ch11p15-pter. Analysis of polymerase chain reaction-amplified short tandem repeats of informative loci confirmed the loss of chY in all lines and loss of heterozygosity (LOH) at eight loci spanning the length of ch8 in all lines from Tx's 1 and 2. Our data support previous studies indicating the presence of tumor suppressor genes on ch8. LOH also was confirmed on ch14 at locus D14S306 in all cell lines from Tx 2 and in one of two lines from Tx 3. This region, 14q12-q13, may contain changes in one of the five known somatostatin receptor genes (SSTR1). No LOH was detected at any of the informative loci tested for on ch4 or ch11.