Assessing the ability of topiramate to improve the daily activities of patients with migraine

OBJECTIVE: To assess the impact of topiramate on the daily activities of patients with migraine. PATIENTS AND METHODS: We performed a randomized, double-blind, placebo-controlled multicenter trial Initiated on March 1, 2001, and completed on April 4, 2002. Patient-reported data from the Migraine Specific Questionnaire (MSQ) and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36) were collected at baseline and at weeks 8, 16, and 26 from an intent-to-treat population receiving either topiramate, 50, 100, or 200 mg/d, or placebo. Two activity-related MSQ domains (role restrictive [MSQ-RR] and role prevention [MSQ-RP]) and 2 activity-related SF-36 domains (role physical [SF36-RP] and vitality [SF36-VT]) were the prospectively designated secondary outcome measures. The changes in MSQ and SF-36 scores for each treatment group were calculated by measuring the area under the curve from week 8 (the beginning of the maintenance period) through week 26 of the double-blind phase, relative to the prospective baseline. A mixed-effect piecewise linear regression model was used to estimate average domain score over time. RESULTS: Patients receiving topiramate, 100 or 200 mg/d, had significantly reduced mean monthly (28-day) migraine frequency (P = .008 and P < .001, respectively) compared with placebo, but not patients receiving topiramate, 50 mg/d (P = .48). Topiramate significantly improved mean MSQ-RR domain scores (50 mg/d [P = .02], 100 mg/d [P< .001], and 200 mg/d [P < .001]) and mean MSQ-RP domain scores (50 mg/d [P = .007], 100 mg/d [P = .001], and 200 mg/d [P= .002]) vs placebo. Topiramate, 100 and 200 mg/d, significantly improved mean SF36-RP domain scores vs placebo (P = .02). Topiramate (all doses) improved SF36-VT domain scores, although not significantly vs placebo. Changes in prospectively designated domain scores were significantly correlated with changes in mean monthly migraine frequency (P < or = .001 [MSQ domains], P < or = .002 [SF-36 domains]). CONCLUSION: Patient-reported migraine-specific outcomes measured by the MSQ-RR and MSQ-RP domains improved significantly for those receiving topiramate (all doses) vs placebo. The SF36-RP domain scores improved significantly for patients receiving 100 or 200 mg/d of topiramate. Improvements in all 4 prospectively selected MSQ and SF-36 domains were significantly correlated with decreases in mean monthly migraine frequency.     

Does tape facilitate or inhibit the lower fibres of trapezius?

The application of tape to the skin overlying the lower fibres of trapezius is generally thought to facilitate this muscle. However, this facilitation has not been thoroughly investigated. In this study, the effect of tape upon trapezius motoneurone pool excitability was assessed using the trapezius H reflex. The amplitude of the H reflex was measured across four conditions: before tape application, with Endura Fix tape, with the addition of Endura Sports tape and finally with the tape removed. Instead of the expected facilitation of lower trapezius, this tape inhibited lower trapezius activity. On average, the application of Endura Fix tape inhibited trapezius by 4%. The application of Endura Sports tape overlaying the Endura Fix tape inhibited trapezius on average by 22%. This inhibition did not last once the tape was removed. This suggests that any change in shoulder girdle symptoms or movement, which occurs with the application of this particular tape, is not explicable on the basis of the facilitation of the lower fibres of trapezius.     

N-oxides of phenothiazine antipsychotics: effects on in vivo and in vitro estimates of dopaminergic function

Although it is known that N-oxidation is a major route for the metabolism of tertiary amine drugs in humans, the extent to which N-oxide (NO) metabolites of clinically used phenothiazine antipsychotics contribute to the neuropharmacology of the parent drug has been uncertain. After direct lateral ventricular injection of rats, both fluphenazine-NO and trifluoperazine-NO (piperazinyl-4-NO) had significant antidopaminergic activity as shown by their antagonism of amphetamine-induced locomotion and, to a lesser extent, of apomorphine-induced stereotypy. In vitro, fluphenazine-NO and trifluoperazine-NO inhibited both [3H]spiperone binding to rat striatal membranes and dopamine-stimulated adenylate cyclase activity in striatal homogenates. Conversely, chlorpromazine (CPZ)-NO (side-chain oxide) did not have significant antidopaminergic activity in either in vitro test, nor did it block amphetamine or apomorphine-induced behavior when centrally administered. These latter results were surprising because it had been reported that CPZ-NO had significant antidopaminergic activity when administered by i.p. injection. In our experiments, i.p. administration of CPZ-NO or CPZ resulted in increased concentrations in brain of the acidic metabolites of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid. However, for CPZ-NO, this was shown to occur concomitantly with the peripheral conversion of the NO back to the parent drug. This suggests that although CPZ-NO does not itself have antidopaminergic properties, it may be readily converted to CPZ or other active species that contribute to pharmacological responses. These data suggest that the NOs of the phenothiazines may contribute to the neuropharmacological actions of antipsychotic drugs via several mechanisms, and underscore the necessity of correlating metabolic and neuropharmacological data.     

Trash and brush burning: an underappreciated mechanism of thermal injury in a rural community

Open-fire injuries associated with burning trash or brush result in a significant number of burn admissions annually. Trash- and brush-burning injuries are more prevalent in rural environments where open burning is an acceptable practice of waste disposal. These injuries are not "unavoidable accidents" but follow a predictable injury pattern. Understanding this injury pattern is paramount to effective prevention. The purpose of this work is to describe the epidemiology of burn injuries associated with burning trash or brush. Charts were retrospectively reviewed for all trash and brush burning injuries from July 1989 to December 2000. One hundred ninety-four injuries were identified, accounting for one fifth of all flame admissions for the study period. Persons most at risk for these burn injuries were males between the ages of 25 to 45, followed by males ages 16 to 24. Accelerant use was identified in over 80% of these injuries. The median cost for admission was $9,363.00 US dollars. Cost was significantly related to age, percent body surface area burned, and operative intervention. Brush and trash burning can lead to costly injuries especially when accelerants are used. Additional research is needed to explore the cultural and social influences associated with these injuries to target effective prevention.     

Measuring processing load during sentence comprehension: Visuomotor tracking

This investigation examined processing load during aspects of sentence comprehension in non-brain-damaged subjects. Our goals were to begin the process of quantifying the loads associated with on-line and off-line aspects of sentence processing and to evaluate the utility of visuomotor tracking as an index of the resource demand associated with elements of sentence comprehension. Subjects were required to track an unpredictable visual target with their forefinger while listening to sentences and answering Yes-No comprehension questions. In general, tracking performance declined during the off-line task of responding to questions compared to the on-line task of listening to sentences and questions. Performance was also poorer during the beginning and end of the sentence compared to the middle of the sentence. Results are discussed in relation to resource theories of normal and aphasic sentence comprehension.     

Treating agrammatic aphasia within a linguistic framework: Treatment of Underlying Forms

Background : Formal linguistic properties of sentences—both lexical, i.e., argument structure, and syntactic, i.e., movement —as well as what is known about normal and disordered sentence processing and production, were considered in the development of Treatment of Underlying Forms (TUF), a linguistic approach to treatment of sentence deficits in patients with agrammatic aphasia. TUF is focused on complex, non-canonical sentence structures and operates on the premise that training underlying, abstract, properties of language will allow for effective generalisation to untrained structures that share similar linguistic properties, particularly those of lesser complexity. Aims : In this paper we summarise a series of studies focused on examining the effects of TUF. Methods & Procedures : In each study, sentences selected for treatment and for generalisation analysis were controlled for their lexical and syntactic properties, with some structures related and others unrelated along theoretical lines. We use single-subject experimental designs—i.e., multiple baseline designs across participants and behaviours—to chart improvement in comprehension and production of both trained and untrained structures. One structure was trained at a time, while untrained sentences were tested for generalisation. Participants included individuals with mild to moderately severe agrammatic, Broca's aphasia with characteristic deficits patterns. Outcomes & Results : Results of this work have shown that treatment improves the sentence types entered into treatment, that generalisation occurs to sentences which are linguistically related to those trained, and that treatment results in changes in spontaneous discourse in most patients. Further, we have found that generalisation is enhanced when the direction of treatment is from more to less complex structures, a finding that led to the Complexity Account of Treatment Efficacy (CATE, Thompson, Shapiro, Kiran, & Sobecks, 2003). Finally, results of recent work showing that treatment appears to affect processing of trained sentences in real time and that treatment gains can be mapped onto the brain using functional magnetic resonance imaging (fMRI) are discussed. Conclusions : These findings indicate that TUF is effective for treating sentence comprehension and production in patients who present with language deficit patterns like those seen in our patients. Patients receiving this treatment show strong generalisation effects to untrained language material. Given the current healthcare climate, which limits the amount of treatment that aphasic patients receive following stroke, it is important that clinicians deliver treatment that results in optimal generalisation in the least amount of time possible.     

IN VITRO STIMULATION OF ANTIBODY FORMATION BY PERITONEAL CELLS : I. PLAQUE TECHNIQUE OF HIGH SENSITIVITY ENABLING ACCESS TO THE CELLS

An improved method for the short-term culture of mouse peritoneal cells in a medium containing carboxymethylcellulose (CMC), sheep erythrocytes (SRBC), and guinea pig complement is described. It involves preparation of microcultures, of thickness 12–15 µ and volume 3.6 µl, under paraffin oil. With such cultures, peritoneal cells from normal, unimmunized young male CBA mice give about 3000 hemolytic plaques per million cells cultured, this figure being attained within 24 hr. The plaque detection method is about four times as sensitive as the Jerne technique. A method is described whereby such plaque-forming cells (PFC) can be transferred, by micromanipulation, to fresh monolayer cultures containing SRBC, CMC, and complement. In this fashion, the secretory capacity and susceptibility to inhibitors of peritoneal PFC can be tested in detail. Using this technique, evidence is presented that the hemolytic substance responsible for plaque formation is actually secreted by the cell at the center of the plaque, and is not a complement component but probably an antibody. Studies on the time of plaque appearance after cell transfer, and the subsequent growth rate of the zone of hemolysis, have been performed. They speak against the idea that the PFC is either a reservoir of cytophilic antibody or a "background" PFC. Rather they suggest that active antibody secretion is induced in the cell at some defined time point in culture. Detailed kinetics of the rate of appearance of plaques in peritoneal cell cultures revealed an exponential phase lasting from about 3 to about 13 hr with a doubling time of 2 hr. The reasons for this are not known. A greatly heightened reactivity was shown in peritoneal cells of mice that had been pregnant several times. Cultures of such cells showed more rapid plaque appearance and a peak activity about 20 times higher than with cells from young male mice. Cultures in which 1 cell in 10 formed a plaque were not infrequent. A series of experiments on germ-free mice showed reactivity similar to that of conventional mice from the same strain and source. The significance of the findings for cellular immunology are discussed.     

CANINE SYSTEMIC LUPUS ERYTHEMATOSUS : GENETIC ANALYSIS OF AN ESTABLISHED BREEDING COLONY

Three breeding lines, originating from dogs with SLE, have been established. Two lines were initiated by mating a female with SLE with a normal male. The third line resulted from a mating of two affected dogs. Brother-to-sister matings have reached the third generation in each line. In addition, backcross and outcross matings were carried out. More than one-third of the autopsied dogs had thymic abnormalities. The commonest lesion was a lymphoid follicle; the thymus of one dog contained multiple granulomas, and in one animal a reticulum cell sarcoma of the thymus was found. Multiple serological abnormalities, including positive LE cell tests, anti-nuclear antibodies (ANA), and rheumatoid factor, were found in the progeny. The development of ANA appeared unrelated to the incidence of positive LE cell tests. About 10% of the animals had rheumatoid factor in their serum. Control populations of dogs; including house pets; two other, unrelated lines of inbred dogs; and normal dogs housed in the same facility as the SLE colony did not have these abnormalities. The incidence of positive LE cell tests in the inbred, backcross, and outcross matings was not consistent with any conventional genetic mechanism of inheritance. It is conceivable that the results can be explained by vertical transmission of an infectious agent in a genetically susceptible individual.