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Biomedical subjects

E A MacGregor

Publications and source records attributed to E A MacGregor.

At least 37 records · Page 2Linked to original sources

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↗

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↗

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↗

Zolmitriptan clinical studies.

Zolmitriptan, a selective 5-HT(1B/D) agonist was developed for the acute treatment of migraine. Dose-finding studies show a clearly defined dose response curve for the oral formulation with onset of efficacy demonstrated within 45 min of dosing. Clinical trials support its efficacy in all types of migraine, with excellent safety and tolerability in those patients for whom zolmitriptan is not contraindicated. Future developments, including new formulations, will provide patients with a greater choice of treatment.

Journal Article↗

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↗

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↗

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↗

A circularly permuted alpha-amylase-type alpha/beta-barrel structure in glucan-synthesizing glucosyltransferases.

A motif of amino acid residues, located at the active site and specific beta-strands in alpha-amylases, is recognized in alpha-1,3- and alpha-1,6-glucan-synthesizing glucosyltransferases, leading to the conclusion that these enzymes contain an alpha/beta-barrel closely related to the (beta/alpha)8-fold of the alpha-amylase superfamily. The secondary structure elements of the transferase barrel, however, are circularly permuted to start with an alpha-helix equivalent to helix 3 in the alpha-amylases. Thus, the transferase counterpart of the long third beta-->alpha connection--constituting a domain in the alpha-amylases--is divided to precede and succeed the barrel. This architectural arrangement may be coupled to sucrose scission and glucosyl transfer. The involvement in the mechanism in glucosyltransferases of active site residues recurring in amylolytic enzymes is discussed.

Amino Acid Sequence↗

"Menstrual" migraine: towards a definition.

"Menstrual" migraine, a term misused by both patients and doctors, lacks precise definition. This dissertation critically reviews papers on the subject and examines the problem from a clinical perspective. A definition is proposed that the term "menstrual" migraine should be restricted to attacks exclusively starting on or between day 1 +/- 2 days of the menstrual cycle; the woman should be free from attacks at all other times of the cycle. This definition, unlike many used previously, links to a specific mechanism; the timing is consistent with oestrogen withdrawal. If this is correct, "oestrogen withdrawal" migraine may be a better term. Future studies, necessary to support or refute these proposals, are suggested.

Diagnosis, Differential↗

Migraine consultations: a triangle of viewpoints.

Several studies have examined patients' attitudes to a consultation for migraine and other headaches. However, a patient's assessment of the problem for which they seek treatment may differ from that of the referring primary physician which may, in turn, differ from the specialist's. This study set out to examine this triangle. The commonest reason for referral was failure of treatment response. This contrasted with the patient's different perception--an increase in the frequency of attacks which we saw as headaches additional to migraine, accounting for failed treatment. Similarly, our view of the patient wanting reassurance paralleled their request for further information. These findings confirmed the hypothesis that recognizing and understanding a patient's fears were important factors towards a favorable outcome of a consultation.

Adolescent↗

Is abdominal pain a feature of adult migraine?

Recurrent abdominal pain in children, frequently diagnosed as "abdominal migraine," is thought to evolve into more typical migraine headache during the teens and twenties. If this transformation occurred, we would expect some adult migraineurs to retain abdominal pain; but we could not recall this symptom being mentioned by patients. However, without direct questioning the absence cannot be assumed. We, therefore, asked 100 migraineurs about abdominal symptoms during migraine attacks: only one experienced unexplained abdominal pain. We conclude that abdominal pain is not a feature in adult migraineurs, leading us to support the notions that: (1) recurrent abdominal pain of childhood has a number of causes; (2) abdominal migraine may be an incorrect attribution and is liable to be over diagnosed; (3) abdominal migraine requires more precise definition; (4) the transition from childhood abdominal migraine to adult migraine needs precise prospective study.

Abdominal Pain↗

Models for the action of barley alpha-amylase isozymes on linear substrates.

The formation of maltodextrins, G1 to G12, during the hydrolysis of amylose by alpha-amylases 1 and 2 from barley malt was followed by HPLC. Similar, but not identical, distributions of products were obtained with the two alpha-amylase components. Maltose, G6, and G7 were major products, but G7 was degraded as hydrolysis proceeded. alpha-Amylase 1 produced more G1 and G3 than did alpha-amylase 2 at all stages of hydrolysis. Products formed during the hydrolysis of G9, G10, G11, and G12 by the two alpha-amylases were also determined. A different spectrum of products was observed with each substrate and small differences were observed in the action pattern of the two alpha-amylases, e.g., G3 and G7 were the major products formed during the hydrolysis of G10 by alpha-amylase 1, whereas G2 and G8 were the major products formed by alpha-amylase 2 on the same substrate. These results were used to develop a model of the active site of barley malt alpha-amylases. This site contains ten contiguous subsites with the catalytic site situated between subsites 7 and 8. The model can be used to predict hydrolysis patterns of amylose and maltodextrins by cereal alpha-amylases.

Carbohydrate Sequence↗

Migraine and the neck.

Fifty patients with migraine were asked about the occurrence of neck symptoms during different phases of their attacks, and if they felt the neck could act as a precipitant. Of the 32 reporting neck pain or stiffness, 10 noted symptoms during the premonitory phase, 30 during the headache phase, and 10 postdromally. In 7 cases the pain radiated into the shoulder and in 1 case into the lumbar region. These findings indicate extracerebral involvement of the migraine process and an overlap between the trigeminal and cervical distribution.

Adolescent↗