Topiramate in migraine prevention: a double-blind, placebo-controlled study.

OBJECTIVE: To evaluate the efficacy of topiramate in the preventative treatment of episodic migraine. BACKGROUND: Topiramate is a broad-spectrum antiepileptic drug effective for treatment of multiple seizure types in adults and children. Antiepileptic agents have demonstrated efficacy in migraine prevention, and open-label experience from our clinic has suggested that topiramate might be effective for this use. We consequently conducted a single-center, double-blind, placebo-controlled trial to evaluate the efficacy and safety of topiramate for the preventative treatment of migraine. METHODS: Forty patients, aged 19 to 62 years (mean, 38.2 years), were randomly assigned in a 1:1 ratio to receive topiramate (n = 19; all women) or placebo (n = 21; 20 women, 1 man). Following a prospective baseline phase of 4 weeks, the study drug dose was titrated weekly in 25-mg increments over 8 weeks to 200 mg per day or to the maximum tolerated dose. The titration phase was followed by an 8-week maintenance phase. RESULTS: During the entire double-blind phase, topiramate-treated patients experienced a significantly lower 28-day migraine frequency (3.31 +/- 1.7 versus 3.83 +/- 2.1; P =.002) compared to placebo, irrespective of use of concomitant migraine prevention medications. The mean 28-day migraine frequency was reduced by 36% in patients receiving topiramate as compared with 14% in patients receiving placebo (P =.004). Twenty-six percent of the patients on topiramate and 9.5% of the patients on placebo achieved a 50% reduction in migraine frequency (P >.05). The mean dose of topiramate was 125 mg per day (range, 25 to 200 mg per day). Topiramate was well tolerated; 2 of 19 topiramate-treated patients discontinued treatment due to adverse events. Adverse effects that occurred more frequently in topiramate-treated patients included paresthesia, weight loss, altered taste, anorexia, and memory impairment. CONCLUSIONS: Preventative therapy with topiramate significantly reduced migraine frequency. Larger multicenter clinical studies may further delineate the role of topiramate in migraine prevention.

Conservation of a CD1 multigene family in the guinea pig.

CD1 is a family of cell-surface molecules capable of presenting microbial lipid Ags to specific T cells. Here we describe the CD1 gene family of the guinea pig (Cavia porcellus). Eight distinct cDNA clones corresponding to CD1 transcripts were isolated from a guinea pig thymocyte cDNA library and completely sequenced. The guinea pig CD1 proteins predicted by translation of the cDNAs included four that can be classified as homologues of human CD1b, three that were homologues of human CD1c, and a single CD1e homologue. These guinea pig CD1 protein sequences contain conserved amino acid residues and hydrophobic domains within the putative Ag binding pocket. A mAb specific for human CD1b cross-reacted with multiple guinea pig CD1 isoforms, thus allowing direct analysis of the structure and expression of at least a subset of guinea pig CD1 proteins. Cell-surface expression of CD1 was detected on cortical thymocytes, dermal dendritic cells in the skin, follicular dendritic cells of lymph nodes, and in the B cell regions within the lymph nodes and spleen. CD1 proteins were also detected on a subset of PBMCs consistent with expression on circulating B cells. This distribution of CD1 staining in guinea pig tissues was thus similar to that seen in other mammals. These data provide the foundation for the development of the guinea pig as an animal model to study the in vivo function of CD1.

Major antigenic proteins of the agent of human granulocytic ehrlichiosis are encoded by members of a multigene family.

Western blot analysis of proteins from a cell culture isolate (USG3) of the human granulocytic ehrlichiosis (HGE) agent has identified a number of immunoreactive proteins, including major antigenic proteins of 43 and 45 kDa. Peptides derived from the 43- and 45-kDa proteins were sequenced, and degenerate PCR primers based on these sequences were used to amplify DNA from USG3. Sequencing of a 550-bp PCR product revealed that it encodes a protein homologous to the MSP-2 proteins of Anaplasma marginale. Concurrently, an expression library made from USG3 genomic DNA was screened with granulocytic Ehrlichia (GE)-positive immune sera. Analysis of two clones showed that they contain one partial and three full-length highly related genes, suggesting that they are part of a multigene family. Amino acid alignment showed conserved amino- and carboxy-terminal regions which flank a variable region. The conserved regions of these proteins are also homologous to the MSP-2 proteins of A. marginale; thus, they were designated GE MSP-2A (45 kDa), MSP-2B (34 kDa), and MSP-2C (38 kDa). The PCR fragment obtained as a result of peptide sequencing was completely contained within the msp-2A clone, and all of the sequenced peptides were found in the GE MSP-2 proteins. Recombinant MSP-2B protein and an MSP-2A fusion protein were expressed in Escherichia coli and reacted with human sera positive for the HGE agent by immunofluorescence assay. These data suggest that the 43- and 45-kDa proteins of the HGE agent are encoded by members of the GE MSP-2 multigene family.

Molecular cloning and sequencing of three granulocytic Ehrlichia genes encoding high-molecular-weight immunoreactive proteins.

Granulocytic Ehrlichia was isolated from canine blood obtained from animals challenged with field-collected Ixodes scapularis and propagated in HL60 cells. PCR primers specific for the 16S ribosomal DNA (rDNA) of the Ehrlichia genogroup comprising E. equi, E. phagocytophila, and the agent of human granulocytic ehrlichiosis (HGE) amplified DNA from extracts of these cells. Sequence analysis of this amplified DNA revealed that it is identical to the 16S rDNA sequence of the HGE agent. A genomic library was constructed with DNA from granulocytic Ehrlichia and screened with pooled sera from tick-challenged, granulocytic Ehrlichia-infected dogs. Several clones were isolated and sequenced. Three complete genes encoding proteins with apparent molecular masses of 100, 130, and 160 kDa were found. The recombinant proteins reacted with convalescent-phase sera from dogs and human patients recovering from HGE. This approach will be useful for identifying candidate diagnostic and vaccine antigens for granulocytic ehrlichiosis and aid in the classification of genogroup members.

Ganciclovir in the treatment of progressive AIDS-related polyradiculopathy.

We present 7 HIV-infected patients with a unique, subacute, progressive polyradiculopathy. All had AIDS, sacral sensory loss, acute urinary retention, and progression to flaccid paraparesis in days to weeks. Cytomegalovirus was cultured from spinal fluid of 4 patients, and postmortem examination of the 1st 5 patients disclosed an inflammatory polyradiculopathy with cytomegalic inclusions. The inclusion-bearing cells were immunocytochemically positive for cytomegalovirus. Two patients who received early anti-cytomegalovirus treatment with ganciclovir improved. Thus, early recognition and treatment with ganciclovir may be effective in this otherwise fatal condition.

Air embolism may cause unrecognized ischemia of the gray-white junction.

The border between the gray and white matter is defined by an abrupt change in average blood flow. This difference allows one to distinguish structure with [14C]iodoantipyrine autoradiography. The angioarchitecture of the cortical gray-white junction suggests that an air embolism might preferentially lodge in this border zone, and thus ischemia of the border might go unrecognized if one depended only on the difference in average blood flow to define the gray-white junction. Accordingly, a computerized image processing technique was applied to compare the area of the cortex measured on an autoradiogram to the area measured on a histologic section after staining for myelin. In dogs that had received air embolism, the autoradiogram underestimated the thickness of the cortical mantle even in sections that did not seem to have an obvious focal zone of low blood flow. This suggests that the deep cortical layers are especially vulnerable to air embolism.

Transfer of beta-lactamase-associated cefoxitin resistance in Bacteroides fragilis.

A cefoxitin-resistant Bacteroides fragilis isolate, TAL 4170, which inactivates cefoxitin, was able to transfer beta-lactamase-mediated cefoxitin resistance to a susceptible B. fragilis recipient. Cefoxitin-resistant transconjugants acquired a new beta-lactamase with a pI of 8.1 and were able to inactivate cefoxitin and retransfer cefoxitin resistance. No plasmids were detected in the donor or transconjugants.