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Biomedical subjects

E A MacGregor

Publications and source records attributed to E A MacGregor.

At least 19 recordsLinked to original sources
PubMed2002

Zolmitriptan orally disintegrating tablet is effective in the acute treatment of migraine.

A new formulation of zolmitriptan has been developed that dissolves on the tongue without the need for additional fluid intake. In this double-blind, parallel study, 471 patients were randomized to receive the zolmitriptan orally disintegrating tablet 2.5 mg (n=231) or matching placebo (n=240) to treat a single moderate or severe migraine. Headache relief following zolmitriptan 2.5 mg (63%) was significantly greater than with placebo (22%) at 2 h post-dose (primary endpoint; P < 0.0001). The zolmitriptan orally disintegrating tablet was also significantly more effective than placebo for 1-, 2- and 4-h pain-free response (8% vs. 3%, P=0.0207, 27% vs. 7%, P < 0.0001, and 37% vs. 11%, P < 0.0001, respectively). Of those patients stating a preference, 70% of patients preferred the orally disintegrating tablet to a conventional tablet. Zolmitriptan orally disintegrating tablets are an effective and convenient alternative to a conventional tablet, allowing migraine attacks to be treated anytime a migraine strikes, which can facilitate earlier treatment.

Administration, Oral↗
PubMed2001

Relationship of sequence and structure to specificity in the alpha-amylase family of enzymes.

The hydrolases and transferases that constitute the alpha-amylase family are multidomain proteins, but each has a catalytic domain in the form of a (beta/alpha)(8)-barrel, with the active site being at the C-terminal end of the barrel beta-strands. Although the enzymes are believed to share the same catalytic acids and a common mechanism of action, they have been assigned to three separate families - 13, 70 and 77 - in the classification scheme for glycoside hydrolases and transferases that is based on amino acid sequence similarities. Each enzyme has one glutamic acid and two aspartic acid residues necessary for activity, while most enzymes of the family also contain two histidine residues critical for transition state stabilisation. These five residues occur in four short sequences conserved throughout the family, and within such sequences some key amino acid residues are related to enzyme specificity. A table is given showing motifs distinctive for each specificity as extracted from 316 sequences, which should aid in identifying the enzyme from primary structure information. Where appropriate, existing problems with identification of some enzymes of the family are pointed out. For enzymes of known three-dimensional structure, action is discussed in terms of molecular architecture. The sequence-specificity and structure-specificity relationships described may provide useful pointers for rational protein engineering.

Amino Acid Sequence↗
PubMed2001

Information about migraine disability influences physicians' perceptions of illness severity and treatment needs.

OBJECTIVE: To assess physician-patient communication about headache-related disability and to evaluate the influence of information about disability on physicians' perceptions of illness severity and the treatment needs of migraineurs. BACKGROUND: Evidence suggests that migraine is suboptimally treated in clinical practice, partly due to poor communication between physicians and their patients. METHODS: One hundred five neurologists and primary care physicians with an interest in headache participated in two interactive surveys, one in North America (n=42) and one in Europe (n=63). Each survey focused on the evaluation of four videotaped migraine cases. The first case was evaluated twice, initially after a typical symptom history that centered on diagnosis and then following a fuller history of migraine disability. Additional questions assessed the extent of the collection of migraine disability information in clinical practice. RESULTS: Physicians reported that they recorded symptoms relating to diagnosis (eg, pain location/intensity, associated symptoms) rather than information on headache-related disability. Only about one third of patients volunteered disability information. When made available to them, physicians rated information on disability as one of the most important factors in assessing treatment needs. In particular, when physicians knew the patient's disability history: (1) the proportion of physicians who rated the patient's illness as "severe" increased by 128% in North America, 27% in Europe; (2) the proportion of physicians who recommended immediate treatment increased by 63% in North America, 37% in Europe; and (3) the proportion of patients recommended for a follow-up visit increased by 15% in North America, 18% in Europe. CONCLUSIONS: Physicians and patients often fail to discuss headache-related disability during consultation. This information has a powerful influence on physicians' perceptions of illness severity, treatment choice, and the need for follow-up. Tools to improve communication about headache-related disability, such as the Migraine Disability Assessment questionnaire, may favorably improve migraine management.

Adult↗
PubMed2001

Migraine-related disability: impact and implications for sufferers' lives and clinical issues.

Migraine is a common, debilitating disorder that imposes a large personal burden on sufferers and high economic costs on society. Sufferers have a significant level of migraine-related disability in all aspects of their daily lives, including employment, household work, and non-work activities. Despite this burden of illness, physicians often do not diagnose or treat the illness effectively. Physicians consider that specific treatment is necessary when disability information is known but, until recently, no criteria have been available for assessment of migraine severity. Two studies indicate that information on disability is an important criterion in assessing migraine severity and influences physicians in their judgments of illness severity and treatment needs. However, physicians and patients often do not seek or share migraine-associated disability, which may contribute to suboptimal management. Efforts to improve knowledge of headache-related disability in the consultation have the potential to improve migraine management. An assessment tool that could reliably quantify headache-related disability has the potential for grading migraine severity and improving care.

Disability Evaluation↗
PubMed2000

Contraception.

The supremacy of combined oral contraceptives (OCs) is being challenged. For too long combined OCs have been seen as synonymous with contraception, helping to maintain ignorance of alternative methods. Further, the efficacy of these OCs and condoms is often compromised by incorrect or inconsistent use. We particularly welcome developments in male systemic methods, that allow men to share not only in conception but also in contraception, and methods that are completely forgettable once instituted, especially if usable by adolescents.

Contraception↗
PubMed2000

Risks and benefits of hormone replacement therapy.

Menopause, the permanent cessation of menstruation, is due to ovarian failure, which may lead to oestrogen deficiency diseases, particularly osteoporosis, cardiovascular disease and cerebrovascular disease. Mortality and morbidity caused by these conditions can be modified by using hormone replacement therapy, but the benefits of this therapy must be weighed against the increased risk of breast cancer and the symptomatic side-effects the treatment may cause. The combination of transdermal oestrogen and natural progesterone offers the most favourable risk-to-benefit profile.

Breast Neoplasms↗
PubMed1999

Migraine in a specialist menopause clinic.

OBJECTIVES: Epidemiological studies suggest that migraine and headache worsen during the climacteric. The authors noted that women attending a specialist hospital-based menopause clinic frequently reported vasomotor and other common climacteric symptoms but few spontaneously reported headache or migraine. The aim of this study was to assess the prevalence of migraine and headache in women attending this clinic. METHODS: Seventy-four women consecutively attending the menopause clinic at St. Bartholomew's Hospital were questioned about headache. Those with a positive response were further interviewed to obtain a headache diagnosis. RESULTS: Headache was found to be a common symptom affecting 57% of women in the 3 months before attending a specialist menopause clinic. Migraine affected 29% of patients in the preceding 3 months. This condition was associated with significant disability: 80% of women reported that attacks were more frequent than once a month; 75% reported that the attacks were severe; 50% reported that the duration of treated attacks was longer than 1 day. DISCUSSION: The high prevalence of headache and migraine in this group suggests that perimenopausal women should routinely be asked about headache and offered appropriate advice. This should include optimal attack therapy and strategies for preventing attacks, which may include hormone replacement therapy (HRT). Further studies are warranted to evaluate the relationship between climacteric symptoms, headaches, migraine and HRT.

Adolescent↗
PubMed1998

Substrate binding and catalytic mechanism of a barley beta-D-Glucosidase/(1,4)-beta-D-glucan exohydrolase.

A beta-glucosidase, designated isoenzyme betaII, from germinated barley (Hordeum vulgare L.) hydrolyzes aryl-beta-glucosides and shares a high level of amino acid sequence similarity with beta-glucosidases of diverse origin. It releases glucose from the non-reducing termini of cellodextrins with catalytic efficiency factors, kcat/Km, that increase approximately 9-fold as the degree of polymerization of these substrates increases from 2 to 6. Thus, the enzyme has a specificity and action pattern characteristic of both beta-glucosidases (EC 3.2.1.21) and the polysaccharide exohydrolase, (1,4)-beta-glucan glucohydrolase (EC 3.2.1.74). At high concentrations (100 mM) of 4-nitrophenyl beta-glucoside, beta-glucosidase isoenzyme betaII catalyzes glycosyl transfer reactions, which generate 4-nitrophenyl-beta-laminaribioside, -cellobioside, and -gentiobioside. Subsite mapping with cellooligosaccharides indicates that the barley beta-glucosidase isoenzyme betaII has six substrate-binding subsites, each of which binds an individual beta-glucosyl residue. Amino acid residues Glu181 and Glu391 are identified as the probable catalytic acid and catalytic nucleophile, respectively. The enzyme is a family 1 glycoside hydrolase that is likely to adopt a (beta/alpha)8 barrel fold and in which the catalytic amino acid residues appear to be located at the bottom of a funnel-shaped pocket in the enzyme.

Amino Acid Sequence↗
PubMed1998

S-fluoxetine in the prophylaxis of migraine: a phase II double-blind randomized placebo-controlled study.

S-fluoxetine is the long-acting enantiomer of the racemic antidepressant serotonin reuptake inhibitor. Sixty-five patients needing migraine prophylaxis were recruited into a phase II, double-blind, placebo-controlled trial. After a 1-month placebo run-in, 53 patients met entry criteria with regard to attack frequency and were randomized, 27 to S-fluoxetine and 26 to matching placebo. Three failed to start treatment and there were 17 early discontinuations, 9 from S-fluoxetine, 8 from placebo, at similar times and for similar reasons. The primary efficacy variable was attack frequency and analysis compared decline-from-baseline in the two groups. This was earlier and greater (1.7 attacks/28 days, or 52%) on active therapy than on placebo (1.1 attacks/28 days, or 27%), and statistically significant in month 2 (F = 4.93; p = 0.033) and month 4 (F = 4.55; p = 0.041). As secondary measures of efficacy, migraine-days per month and Patient's Global Impression of Disease Severity coherently reflected the changes in attack frequency. Mean attack severity and acute medication use (doses per attack) were unaltered by either treatment. There were no serious adverse events. Withdrawals for adverse events were four from each group but none was considered causally related. The finding of greater efficacy of S-fluoxetine than of placebo should be interpreted conservatively, since the analysis in the final month was made on only half of the entered patients. It supports progression to phase III evaluation, which was the purpose of the study.

Adult↗
PubMed1998

Combined oral contraceptives, migraine and ischaemic stroke. Clinical and Scientific Committee of the Faculty of Family Planning and Reproductive Health Care and the Family Planning Association.

The incidence of ischaemic stroke is low in women of reproductive age but increased in women with migraine, particularly if they also take combined oral contraceptives (COCs). Since there is limited evidence that this risk may be further focused on some groups of women with migraine, this paper presents current recommendations for COC use by a confirmed migraineur, pending further data.

Adult↗
PubMed1997

Menstruation, sex hormones, and migraine.

All women with migraine are susceptible to the effects of hormonal changes. For a minority with menstrual migraine, fluctuating hormones of the normal ovarian cycle are a specific trigger, particularly during perimenopause. The author proposes that the term menstrual migraine should be restricted to migraine attacks occurring on day 1 +/- 2 days of the menstrual cycle with freedom from migraine during the rest of the cycle. This definition is compatible with the mechanism of estrogen withdrawal. Other mechanisms such as prostaglandin release also may be important for some women. The changing hormonal environment at various stages of life provides further evidence of the role of estrogen in migraine. Treatments that stabilize hormone levels in the form of estrogen supplementation for menstrual migraine, elimination of the pill-free week, and adequate, stable levels of estrogen for HRT, all are associated with an improvement in migraine. The control of the menstrual cycle, however, is extremely complex, and until further studies are undertaken using strict criteria, the mechanism of migraine triggered by hormonal events remains uncertain.

Female↗
PubMed1997

The doctor and the migraine patient: improving compliance.

Migraine is an underdiagnosed and undertreated disorder. This can be attributed to the low consultation rate for migraine, for which many reasons have been proposed. These include the fact that many migraineurs self-treat and, historically, the lack of available effective treatments. Some migraineurs are referred to specialist centers for advice. These patients do not merely need effective pain relief. They also need an explanation of the cause of the migraine and reassurance that their headache pain does not have a more sinister cause. By spending time with patients and taking a full history of their migraine condition, the physician can propose a management strategy that is appropriate to each individual patient, thus providing a tailored-care approach. Thorough exploration of possible trigger factors for migraine and advice on avoidance may help to reduce attack frequency. Simple techniques can also be used to improve compliance with prescribed therapies. For example, it is important for the physician to establish that the patient understands any instructions given and to reinforce this advice at follow-up visits. Regular follow-up is important because it enables management strategies to be evaluated and helps the patients to feel involved in the management of their migraine. A correct understanding of the way a drug works and the nature of the condition, together with an explanation of any potential side effects, is likely to maximize clinical benefit.

Empathy↗