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.     

Autonomic dysreflexia after spinal cord transection or compression in 129Sv,C57BL,and Wallerian degeneration slow mutant mice

To study plasticity of central autonomic circuits that develops after spinal cord injury (SCI), we have characterized a mouse model of autonomic dysreflexia. Autonomic dysreflexia is a condition in which episodic hypertension occurs after injuries above the midthoracic segments of the spinal cord. As synaptic plasticity may be triggered by axonal degeneration, we investigated whether autonomic dysreflexia is reduced in mice when axonal degeneration is delayed after SCI. We subjected three strains of mice, Wld(S), C57BL, and 129Sv, to either spinal cord transection (SCT) or severe clip-compression injury (CCI). The Wld(S) mouse is a well-characterized mutant that exhibits delayed Wallerian degeneration. The CCI model is an injury paradigm in which significant the axonal degeneration is due to secondary events and therefore delayed relative to the time of the initial injury. We herein demonstrate that the incidence of autonomic dysreflexia is reduced in Wld(S) mice after SCT and in all mice after CCI. To determine if differences in afferent arbor sprouting could explain our observations, we assessed changes in the afferent arbor in each mouse strain after both SCT and CCI. We show that independent of the type of injury, 129Sv mice but not C57BL or Wld(S) mice demonstrated an increased small-diameter CGRP-immunoreactive afferent arbor after SCI. Our work thus suggests a role for Wallerian degeneration in the development of autonomic dysreflexia and demonstrates that the choice of mouse strain and injury model has important consequences to the generalizations that may be drawn from studies of SCI in mice.     

Antiphospholipid and antiprotein syndromes in non-thrombotic, non-autoimmune women with unexplained recurrent primary early foetal loss. The Nîmes Obstetricians and Haematologists Study--NOHA

Various antiphospholipid and/or antiprotein antibodies have been suspected to be associated with recurrent early foetal loss in absence of any habitual aetiology. We conducted a hospital-based case control study on women with no antecedent of thromboembolic or autoimmune disease. We studied 3 groups of 518 women: patients with unexplained primary recurrent early foetal loss, patients with explained episodes and mothers with no previous obstetrical accident. Matching the 3 groups was carried out on the basis of age, number or pregnancies and time elapsed since the end of the last pregnancy. Significant biological markers were then prospectively tested. The various antibodies were shown to be dependent on parity and on the presence of previous foetal loss: cut-off values were thus calculated using data obtained from the group of explained accidents, and adjusted for parity. Only anti-phosphatidylethanolamine IgM [odds ratio: 6.0, 95% confidence interval (2.3-15.7), p = 0.0003], anti-beta2-glycoprotein I IgG [4.4, (1.6-11.7), p = 0.0035] anti-annexin V IgG antibodies [3.2 (1.2-8.1), p = 0.015] and lupus anticoagulant [3.0, (1.3-6.8), p = 0.009], were found to be independent retrospective risk factors for unexplained early foetal loss. These four markers were subsequently found to be, during the following pregnancy, associated with a significant risk of foetal loss despite a low-dose aspirin treatment. In non-thrombotic, non-auto-immune women with unexplained primary recurrent early foetal loss, subgroups of patients with positive anti-phosphatidylethanolamine IgM antibodies, or positive anti-beta2-glycoprotein-I IgG antibodies, or positive anti-annexin V IgG antibodies or lupus anticoagulant must be particularised. This should allow therapeutic trials to be carried in well-defined patients.     

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.      

Mycobacterial infection in an inner city children's hospital

Childhood tuberculosis is perceived by many as a disease of the past. Experience in a children's hospital serving a deprived population suggested that tuberculosis and other mycobacterial infections were not declining in clinical practice. Fifty three tuberculous and 11 atypical mycobacterial infections were identified between 1978 and 1992. There was no decline in tuberculosis and nine of the 11 atypical infections occurred in the last five years. Altogether 40% of cases of tuberculosis were in non-Asian children; 32% had arrived in the UK or visited family overseas in the previous year; and 38% had a history of tuberculosis contact, usually a close adult relative. Nationally, the previous decline in tuberculosis in all ages has reversed. In the local health districts in London's east end, childhood tuberculosis has also stopped declining and seems to be increasing. It is regrettable that BCG vaccination has been abolished by some districts in the UK, against current recommendations. Childhood tuberculosis is still common in the practice described here, including among children who do not fall into conventionally recognised high risk groups. Inner city dwellers and junior doctors are both highly mobile populations, adding to the risk that paediatricians, particularly those in training, may encounter tuberculosis with little or no previous experience of the condition.