Petasites hybridus root (butterbur) is an effective preventive treatment for migraine.

OBJECTIVE: To evaluate the clinical efficacy of a standardized special root extract from the plant Petasites hybridus as a preventive therapy for migraine. METHODS: This is a three-arm, parallel-group, randomized trial comparing Petasites extract 75 mg bid, Petasites extract 50 mg bid, or placebo bid in 245 patients with migraine. Eligible patients met International Headache Society criteria for migraine, were ages 18 to 65, and had at least two to six attacks per month over the preceding 3 months. The main outcome measure was the decrease in migraine attack frequency per month calculated as percentage change from baseline over a 4-month treatment period. RESULTS: Over 4 months of treatment, in the per-protocol analysis, migraine attack frequency was reduced by 48% for Petasites extract 75 mg bid (p = 0.0012 vs placebo), 36% for Petasites extract 50 mg bid (p = 0.127 vs placebo), and 26% for the placebo group. The proportion of patients with a > or =50% reduction in attack frequency after 4 months was 68% for patients in the Petasites extract 75-mg arm and 49% for the placebo arm (p < 0.05). Results were also significant in favor of Petasites 75 mg at 1, 2, and 3 months based on this endpoint. The most frequently reported adverse reactions considered possibly related to treatment were mild gastrointestinal events, predominantly burping. CONCLUSIONS: Petasites extract 75 mg bid is more effective than placebo and is well tolerated as a preventive therapy for migraine. Petasites 50 mg PO bid was not significantly more effective than placebo on the primary study endpoints.

Acetaminophen in the treatment of headaches associated with dipyridamole-aspirin combination.

The authors assessed the prevalence of headaches following extended-release dipyridamole/aspirin combination (DAC), and the efficacy of acetaminophen in the treatment of these headaches. Following DAC, 38.7% of the participants developed headaches. The headaches were self-limited (69.4% placebo efficacy in 2 hours) and the incidence markedly declined over time. Acetaminophen was no more effective than placebo in the acute and preemptive treatment of these headaches.

Diagnostic lessons from the spectrum study.

Article abstract Migraine is a heterogeneous condition that causes symptoms that vary both among individuals and within individuals from attack to attack. We examined and reviewed several important lessons on the diagnosis of migraine learned from the distribution of headache types and patterns of treatment response in the Spectrum Study, including recruitment and diagnostic issues. The accuracy of an initial diagnosis, assigned by a clinician in the context of a clinical trial, was compared with the results of a final diagnosis, assigned by a neurologist, reviewing the initial evaluation as well as headache diaries for up to 10 attacks. Several lessons can be learned from the Spectrum Study. Recruitment difficulties teach us that disabling tension-type headache is difficult to find, suggesting that it is rare. Examination of the final diagnosis given after diary evaluations suggests that a diagnosis of migraine can usually be confirmed for patients with disabling headache. After reclassification of the final sample of 432 subjects, 24/75 (32%) patients initially clinically classified as having disabling episodic tension-type headache proved to have migraine or migrainous headache after a diary review. Among study participants, 90% of subjects with disabling headache (HIMQ score >250) had a migraine-related disorder. Treatment response suggests that, in migraineurs, tension-type headaches may have a pathophysiology similar to that of migraine. The diary data show that mild headaches in patients with disabling migraine often evolve into full-blown migraine. The Spectrum Study supports the view that, for patients with disabling episodic headache, migraine is often the correct diagnosis. In clinical practice, the suspicion of migraine should be high for patients experiencing episodic disabling headache. Assessment of headache-related disability may assist practitioners in making a diagnosis of migraine.

The effects of alginate composition on encapsulated betaTC3 cells.

The effects of alginate composition on the growth of murine insulinoma betaTC3 cells encapsulated in alginate/poly-L-lysine/alginate (APA) beads, and on the overall metabolic and secretory characteristics of the encapsulated cell system, were investigated for four different types of alginate. Two of the alginates used had a high guluronic acid content (73% in guluronic acid residues) with varying molecular weight, while the other two had a high mannuronic acid content (68% in mannuronic acid residues) with varying molecular weight. Each composition was tested using two different polymer concentrations. Our data show that betaTC3 cells encapsulated in alginates with a high guluronic acid content experienced a transient hindrance in their metabolic and secretory activity because of growth inhibition. Conversely, betaTC3 cells encapsulated in alginates with a high mannuronic acid content experienced a rapid increase in metabolic and secretory activity as a result of rapid cell growth. Our data also demonstrate that an increase in either molecular weight or concentration of high mannuronic acid alginates did not alter the behavior of the encapsulated betaTC3 cells. Conversely, an increase in molecular weight and concentration of high guluronic acid alginates prolonged the hindrance of glucose metabolism, insulin secretion and cell growth. These observations can be best interpreted by changes in the microstructure of the alginate matrix, i.e., interaction between the contiguous guluronic acid residues and the Ca2+ ions, as a result of the different compositions.

Mammography screening in single older African-American women: a study of related factors.

OBJECTIVE: Using baseline data from an intervention study, we examined cognitive, psychological, social and medical care factors in relation to the use of a mammogram in the preceding year among single African-American women aged 65 and older. METHODS: Study subjects were 325 African-American women aged 65 and older who were divorced, widowed, separated or never-married, and lived in ten public housing complexes in Nashville, Tennessee. In-person interviews were conducted to collect information on breast screening behavior, knowledge and attitude, social network and activities, emotional and psychological symptoms and signs, and medical care use. RESULTS: Compared with those who had not had a mammogram in the preceding year, women who had had a mammogram in the preceding year were three times more likely to have a regular doctor (95% confidence interval [CI] 1.4-5.0) and about six times more likely to have a doctor's recommendation for a mammogram (95%CI 3.4-11.1). In addition, they were more likely to: (a) have attended a meeting on breast health or received educational materials on breast cancer; (b) agree that a woman needs a mammogram even though she has no breast problem; (c) agree that a woman can have breast cancer without having symptoms; (d) have living children and grandchildren; and (e) attend social activities more frequently. CONCLUSIONS: While access to regular medical care and receiving a physician's recommendation are strongly associated with mammography among these older, single African-American women, education on breast health and social networks also appear to be influential.

An intervention study on screening for breast cancer among single african-american women aged 65 and older.

PURPOSE: Older single African-American women are the population that is least likely to use screening procedures because of cognition-related, income-related, social-support-related and medical care-related barriers. This study aims to evaluate a breast screening intervention program developed according to socioeconomic, cultural, psychological and behavioral characteristics of older single African-American women.METHODS: Ten public housing complexes were randomly assigned to either intervention or control group. African-American women aged 65 and over were recruited into the study if they were widowed, divorced, separated or never-married in the preceding year, and did not have a history of breast cancer (n = 325). Delivered by lay health educators, the intervention program targeted increasing knowledge on breast health and breast screening, reducing emotional or psychological problems, and increasing support from the significant others of study women. Breast screening-related cognition and behavior were measured at pre-intervention and post-intervention.RESULTS: Comparisons of the pre-intervention and post-intervention measurements showed that while the proportion of women who had a clinical breast examination or mammogram in the preceding year was decreased at the post-intervention in the control group, it was increased in the intervention group. However, the differences did not reach a significant level. No consistent patterns could be found in changes of variables in knowledge, attitudes and beliefs. These results remained similar when potential confounding factors were adjusted using mixed model regression analyses.CONCLUSIONS: These results did not suggest significant effects of an intervention program which used lay health educators to promote breast cancer screening in older single African-American women.

Depression-related variables and breast self-examination in single older african-american women.

PURPOSE: Depression-related symptoms, such as despair and loneliness, may prevent women from using preventive screening for diseases. This study aimed to assess if depression-related variables affect the likelihood of implementation of breast self-examination (BSE) in single African-American women aged 65 and older.METHODS: Subjects for this study included 325 African-American women, aged 65 and older, who were widowed, divorced, separated, or never-married, and lived in ten public housing tenements in Nashville, Tennessee. In-person interviews were conducted to collect information on breast screening behavior, knowledge and attitudes, social networks and activities, medical care use and depression. Depression variables included 19 factors, such as feeling guilty, feeling sad or blue, and feeling worthless.RESULTS: Using logistic regression with adjustment for potential confounders, we found that, compared with women who did not perform BSE, those who performed BSE were less likely to have felt guilty in the preceding year (p < 0.05, odds ratio (OR) = 0.3, confidence interval (CI) = 0.13-0.71). However, the other depression-related variables were not associated with BSE. For example, women who performed BSE and those who did not perform BSE reported feeling sad or blue in equal frequencies (OR = 0.93, CI 0.49-1.7).CONCLUSIONS: In general, this study suggests that there is no overall association between depression-related symptoms and breast self-examination in single African-American women aged 65 and older.

Recruiting elderly African-American women in cancer prevention and control studies: a multifaceted approach and its effectiveness.

Barriers to engaging African Americans as research participants may be accentuated among older single African-American women partly because of financial, social, physical, and cognitive factors. This article shows our multifaceted strategies and experiences in the recruitment of single African-American women aged 65 and older in a cancer prevention and control study. The study was conducted in 10 public housing complexes in Nashville, Tennessee. Out of 367 eligible women, 325 participated in the study, resulting in a rate of 89%. The result suggests that a strategy, which targets the cultural, perceptive, and cognitive characteristics of the population, was effective for increasing the enrollment of study subjects in this population. Because the single constitute 75% of African-American women aged 65 and older; and the incidence and mortality of cancer are especially high in elderly African Americans, our experiences are encouraging for cancer prevention and control research in the population.

Natural genetic exchange between Haemophilus and Neisseria: intergeneric transfer of chromosomal genes between major human pathogens.

Members of the bacterial families Haemophilus and Neisseria, important human pathogens that commonly colonize the nasopharynx, are naturally competent for DNA uptake from their environment. In each genus this process is discriminant in favor of its own and against foreign DNA through sequence specificity of DNA receptors. The Haemophilus DNA uptake apparatus binds a 29-bp oligonucleotide domain containing a highly conserved 9-bp core sequence, whereas the neisserial apparatus binds a 10-bp motif. Each motif ("uptake sequence", US) is highly over-represented in the chromosome of the corresponding genus, particularly concentrated with core sequences in inverted pairs forming gene terminators. Two Haemophilus core USs were unexpectedly found forming the terminator of sodC in Neisseria meningitidis (meningococcus), and sequence analysis strongly suggests that this virulence gene, located next to IS1106, arose through horizontal transfer from Haemophilus. By using USs as search strings in a computer-based analysis of genome sequence, it was established that while USs of the "wrong" genus do not occur commonly in Neisseria or Haemophilus, where they do they are highly likely to flag domains of chromosomal DNA that have been transferred from Haemophilus. Three independent domains of Haemophilus-like DNA were found in the meningococcal chromosome, associated respectively with the virulence gene sodC, the bio gene cluster, and an unidentified orf. This report identifies intergenerically transferred DNA and its source in bacteria, and further identifies transformation with heterologous chromosomal DNA as a way of establishing potentially important chromosomal mosaicism in these pathogenic bacteria.

Periplasmic superoxide dismutase in meningococcal pathogenicity.

Meningococcal sodC encodes periplasmic copper- and zinc-cofactored superoxide dismutase (Cu,Zn SOD) which catalyzes the conversion of the superoxide radical anion to hydrogen peroxide, preventing a sequence of reactions leading to production of toxic hydroxyl free radicals. From its periplasmic location, Cu,Zn SOD was inferred to acquire its substrate from outside the bacterial cell and was speculated to play a role in preserving meningococci from the action of microbicidal oxygen free radicals produced in the context of host defense. A sodC mutant was constructed by allelic exchange and was used to investigate the role of Cu,Zn SOD in pathogenicity. Wild-type and mutant meningococci grew at comparable rates and survived equally long in aerobic liquid culture. The mutant showed no increased sensitivity to paraquat, which generates superoxide within the cytosol, but was approximately 1,000-fold more sensitive to the toxicity of superoxide generated in solution by the xanthine/xanthine oxidase system. These data support a role for meningococcal Cu,Zn SOD in protection against exogenous superoxide. In experiments to translate this into a role in pathogenicity, wild-type and mutant organisms were used in an intraperitoneal mouse infection model. The sodC mutant was significantly less virulent. We conclude that periplasmic Cu,Zn SOD contributes to the virulence of Neisseria meningitidis, most likely by reducing the effectiveness of toxic oxygen host defenses.

Identification of sodC encoding periplasmic [Cu,Zn]-superoxide dismutase in Salmonella.

sodC, encoding [Cu,Zn]-cofactored superoxide dismutase, once thought to be virtually confined to eukaryotes, has now been described in many Gram-negative pathogens that have their primary niche of colonization in the upper respiratory tract. Their role in host-parasite interactive biology is unknown. We here show that members of the major human and animal enteric pathogenic species Salmonella harbour a version of sodC most closely resembling that found in Brucella abortus. The enzyme it encodes is a novel candidate determinant of virulence in Salmonella, an intracellular pathogen potentially exposed to toxic oxygen free radicals within its intracellular niche.

Cloning and molecular analysis of the Isi1 (rfaF) gene of Neisseria meningitidis which encodes a heptosyl-2-transferase involved in LPS biosynthesis: evaluation of surface exposed carbohydrates in LPS mediated toxicity for human endothelial cells.

Neisseria meningitidis, but not Haemophilus influenzae, damage cultured human endothelial cells. We have undertaken a study to generate genetically and structurally defined lipopolysaccharide (LPS) mutant strains of meningococci for functional studies to assess the role of surface exposed oligosaccharides in imparting specificity of toxic damage to human endothelial cells. The Isi1 gene, which had been shown to be involved in LPS biosynthesis of Neisseria gonorrhoeae, was amplified by PCR and cloned. Nucleotide sequence analysis confirmed the identity of the clone and revealed homology with Isi1 of N. gonorrhoeae and the rfaF gene of Salmonella typhimurium which encodes a heptosyl-2-transferase involved in LPS biosynthesis. The identity of the cloned Isi1 gene, as a functional rfaF homologue, was confirmed by the complementation of a S. typhimurium rfaF mutant using a P22 phage sensitivity test. An Isi1 mutant meningococcal strain was constructed, and structural analysis of the mutant LPS molecule revealed a single heptose in the core structure, consistent with a heptosyl-2-transferase deficient mutant. In order to investigate the relative cytotoxicities of meningococci expressing native and altered LPS, wild type, Isi1, and galE strains were compared in cytotoxicity assays using human umbilical vein endothelial cells (Huvecs) in culture. Analysis using Huvecs derived from several individuals (cords) showed that the three phenotypes were almost equally cytotoxic. Removal of the terminal portion (galE mutant) or the majority (Isi mutant) of the oligosaccharide did not effect LPS-mediated cytopathic damage to Huvecs in a culture suggesting that the oligosaccharide portion did not play a major role in cytotoxicity.

Bacterial [Cu,Zn]-superoxide dismutase: phylogenetically distinct from the eukaryotic enzyme, and not so rare after all!

Copper- and zinc-containing superoxide dismutases ([Cu,Zn]-SODs) are generally considered almost exclusively eukaryotic enzymes, protecting the cytosol and extracellular compartments of higher organisms from damage by oxygen free-radicals. The recent description of a few examples of bacterial forms of the enzyme, located in the periplasm of different Gram-negative micro-organisms, prompted a re-evaluation of this general perception. A PCR-based approach has been developed and used successfully to identify bacterial genes encoding [Cu,Zn]-SOD in a wide range of important human and animal pathogens-members of the Haemophilus, Actinobacillus and Pasteurella (HAP) group, and Neisseria meningitidis. Comparison of [Cu,Zn]-SOD peptide sequences found in Haemophilus ducreyi, Actinobacillus pleuropneumoniae, Actinobacillus actinomycetemcomitans, Pasteurella multocida, and N. meningitidis with previously described bacterial proteins and examples of eukaryotic [Cu,Zn]-SOD has shown that the bacterial proteins constitute a distinct family apparently widely separated in evolutionary terms from the eukaryotic examples. The widespread occurrence of [Cu,Zn]-SOD in the periplasm of bacterial pathogens, appropriately located to dismute exogenously derived superoxide radical anions, suggests that this enzyme may play a role in the interactive biology of organisms with their hosts and so contribute to their capacity to cause disease.

Cloning and molecular analysis of the galE gene of Neisseria meningitidis and its role in lipopolysaccharide biosynthesis.

The galE gene from Haemophilus influenzae was used as a hybridization probe for the galE gene of Neisseria meningitidis Group B, identifying two different homologous loci. Each of the loci was cloned and nucleotide sequence analysis revealed that both loci contained sequences similar to galE. One contained a functional galE gene and mapped to the capsule biosynthetic locus. The second contained only a partial galE-coding sequence, which did not express a functional gene product. A galE mutant meningococcal strain was constructed by transformation with an inactivated galE gene. Analysis of the LPS from the galE mutant strain revealed an apparent reduction in molecular weight and a loss of reactivity with monoclonal antibodies specific for structures known to contain galactose. These results are consistent with an essential role for galE in the incorporation of galactose into meningococcal lipopolysaccharide.