bluuebunny/crossref_metadata_2025 huggingface dataset:
Sympathetic attenuation of parasympathetic vasodilatation in oro‐facial areas in the cat
Authors: Izumi Hiroshi , Ito Yutaka
Published: September 2004

The present study was designed to examine the interaction between sympathetic and parasympathetic influences on blood flow in oro‐facial areas such as lower lip, palate and submandibular gland (SMG) and in the common carotid artery (CCA) in anaesthetized cats.

Section of the ipsilateral superior cervical sympathetic trunk (CST) increased the basal CCA blood flow significantly. The control level with the nerve intact was comparable with that seen at 0.5‐1 Hz CST stimulation, suggesting a spontaneous discharge of around 0.5‐1 Hz in the CST fibres innervating the beds supplied by the CCA. The basal blood flow at all sites examined was reduced by CST stimulation in a frequency‐dependent manner.

Electrical stimulation of the central end of the lingual nerve (LN) evoked blood flow increases in the lower lip and palate. These blood flow increases were markedly reduced by concurrent CST stimulation in a manner that was frequency dependent, but not simply related to the vasoconstrictor effect of CST stimulation. This effect of CST stimulation was not observed in tongue or SMG, even though CST stimulation evoked vasoconstriction in these tissues. A significant reduction in the level of CCA blood flow attained during LN stimulation was observed on repetitive CST stimulation only at 10 Hz, indicating that this response behaved in a fashion different from that seen in the lower lip, palate, tongue and SMG.

The present study suggests that concurrent repetitive CST stimulation reduces parasympathetically mediated blood flow increases in certain oro‐facial areas (such as the lower lip and palate), but not in the tongue and SMG. This inhibitory action was not a simple additive effect (between vasoconstriction and vasodilatation) and it disappeared rapidly after the cessation of CST stimulation.
The compliance of the porcine pulmonary artery depends on pressure and heart rate
Authors: Kornet L. , Jansen J. R. C. , te Nijenhuis F. C. A. M. , Langewouters G. J. , Versprille A.
Published: September 2004

The influence of mean pulmonary arterial pressure (mean Ppa) on dynamic (Cd) and pseudo‐static compliance (Cps) of the pulmonary artery was studied at a constant and a changing heart rate. Cd is the change in cross‐sectional area (CSA) relative to the change in Ppa throughout a heart cycle. Cps is the change in mean CSA relative to the change in mean Ppa. If Cd is known, pulmonary blood flow can be computed from the Ppa using a windkessel model. We investigated whether Cps can be interchanged with Cd.

In nine anaesthetized pigs, we determined the mean CSA and Cd of the pulmonary artery at various Ppa levels, ranging from approximately 30 to 10 mmHg, established by bleeding. Two series of measurements were carried out, one series at a spontaneously changing heart rate (n= 9) and one series at a constant heart rate (n= 6). To determine CSA a conductance method was used.

C
ps depended on pressure. The mean CSA versus mean Ppa curves were sigmoid and steepest in the series with the increasing heart rate (established by bleeding). The CSA versus Ppa loop during a heart cycle, giving Cd, was approximately linear and almost closed. The Cdversus mean Ppa relationship was bell shaped. Its width was smaller if the heart rate increased during the series of measurements. The pressure, where Cd was maximum, was higher at higher heart rates. Furthermore, the maximum Cd was not affected by the heart rate.

Because the pulmonary artery constricts with increasing heart rate, Cps will be overestimated during procedures where heart rate increases. Cd should be determined on a beat‐to‐beat basis to calculate flow because it changes with mean pulmonary arterial pressure and heart rate.
The canine phrenic‐to‐intercostal reflex
Authors: De Troyer André
Published: September 2004

Paralysis of the diaphragm in the dog causes a non‐vagal, non‐chemical increase in the activity of the inspiratory intercostal muscles. In the present studies, the hypothesis was tested that phrenic afferent fibres may elicit a reflex inhibition of inspiratory intercostal activity.

The electrical activity of the three groups of inspiratory intercostal muscles (parasternal intercostals, external intercostals, levator costae) was recorded in twenty vagotomized, spontaneously breathing dogs, and the proximal end of one or both C5 phrenic nerve roots was stimulated during inspiration.

Stimulation of the ipsilateral and contralateral C5 phrenic roots caused an immediate reduction in inspiratory intercostal activity. This reduction was abolished when phrenic stimulation was repeated after section of the C5 dorsal roots.

The reduction in external intercostal and levator costae activity during bilateral C5 afferent stimulation appeared when the stimulus strength was 3 times the motor threshold and it increased in magnitude when stimulus intensity was increased further. In contrast, the reduction in parasternal intercostal activity occurred only when the stimulus strength was 12 times the motor threshold.

These observations confirm the hypothesis that diaphragmatic receptors may reflexly inhibit efferent activity to the inspiratory intercostal muscles, in particular the external intercostals and levator costae. This inhibition appears to be primarily mediated by small myelinated fibres.
Activity‐dependent hyperpolarization of human motor axons produced by natural activity
Authors: Vagg Rebecca , Mogyoros Ilona , Kiernan Matthew C. , Burke David
Published: September 2004

The changes in excitability of motor axons produced by natural activity were measured in six healthy subjects using voluntary contractions lasting 15 s, 30 s and 1 min, by recording the changes in stimulus current required to produce a compound muscle action potential of ≈60 % of maximum.

On cessation of the contractions there was a prominent increase in the current required to produce the target potential, accompanied by an increase in rheobase, a decrease in strength‐duration time constant, and an increase in axonal supernormality. These changes indicate that the hypoexcitability was due to axonal hyperpolarization.

The activity‐dependent hypoexcitability increased in depth and duration the longer the contraction. Following a 1 min contraction, it produced a 24 % increase in threshold, waning over 15 min. The hypoexcitability was greater than in cutaneous afferents tetanized to produce an equivalent rate‐dependent stress.

It is concluded that natural activity results in substantial hyperpolarization of active axons and that, for similar discharge rates, the degree of hyperpolarization is greater in motor axons than cutaneous afferents. The greater effect of activity on the excitability of motor axons could be due to less inward rectification and less persistent Na+ conductance than in sensory axons. It is suggested that motor axons may therefore be more susceptible than cutaneous afferents to conduction block at sites of impaired safety margin for impulse conduction.
Signalling of static and dynamic features of muscle spindle input by cuneate neurones in the cat
Authors: Mackie P. D. , Morley J. W. , Zhang H. Q. , Murray G. M. , Rowe M. J.
Published: September 2004

The capacity of cuneate neurones to signal information derived from muscle spindle afferent fibres about static stretch or vibration of forearm extensor muscles was examined electrophysiologically in anaesthetized cats.

Static stretch (<= 2 mm in amplitude) and sinusoidal vibration (at frequencies of 50‐800 Hz) were applied longitudinally to individual muscle tendons by means of a feedback controlled mechanical stimulator, and responses were recorded from individual cuneate neurones and from individual spindle afferent fibres.

Cuneate neurones sampled were located caudal to the obex and displayed a sensitivity to both vibration and static stretch of forearm muscles that was consistent with their input arising from primary spindle endings. In response to static muscle stretch, they displayed graded and approximately linear stimulus‐response relations, and a stability of response level at fixed lengths that was consistent with these neurones contributing discriminative information about static muscle stretch.

In response to sinusoidal muscle vibration the cuneate neurones also showed graded stimulus‐response relations (in contrast to spindle afferents which at low vibration amplitudes attain a plateau response level corresponding to a discharge of 1 impulse on each vibration cycle). Lowest thresholds were at 100‐300 Hz and bandwidths of vibration sensitivity extended up to ∼800 Hz.

Temporal precision in cuneate responses to muscle vibration was assessed by constructing phase scatter and cycle histograms from which measures of vector strength could be calculated. Cuneate responses displayed somewhat poorer phase locking (and lower vector strengths) than spindle afferent responses to vibration (a reflection of uncertainties associated with synaptic transmission). Nevertheless, the remarkable feature of cuneate responses to muscle vibration is the preservation of tight phase locking at frequencies up to 400‐500 Hz, which presumably enables these central neurones to contribute accurate temporal information for the kinaesthetic sense in a variety of circumstances involving dynamic perturbations to skeletal muscle.
Muscle history, fusimotor activity and the human stretch reflex
Authors: Gregory J. E. , Wise A. K. , Wood S. A. , Prochazka A. , Proske U.
Published: September 2004

The previous history of contraction and length changes of a muscle influences the size of the stretch reflex and H reflex. Here we ask, is this dependence due to changes in mechanical properties of extrafusal fibres, intrafusal fibres of spindles, or both?

The soleus muscle of human subjects was conditioned using either a voluntary contraction or a contraction evoked by low‐strength electrical stimulation, in the range 0–25% of maximum. Following conditioning, reflexes were increased by more than twofold above the no‐contraction value by a voluntary contraction of 5% of maximum, or more, but not by electrical stimulation which presumably did not contract the intrafusal fibres of spindles.

When the muscle was conditioned with a contraction at a length shorter than the test length, rather than at the test length, a depressing effect on reflexes was attributed to both the burst of impulses generated in spindles when the muscle was stretched back to the test length and to a reduced stretch sensitivity of muscle spindles.

The experiments demonstrate the importance of keeping the muscle and its spindles in a defined mechanical state when measuring reflexes. They also point to the powerful facilitating influences of conditioning muscle contractions provided they recruit the intrafusal fibres of spindles.
Enhanced vasoconstrictor responses in renal and femoral arteries of the golden hamster during hibernation
Authors: Karoon Parastoo , Knight Gillian , Burnstock Geoffrey
Published: September 2004

The present study assessed local regulation of vascular tone of euthermic (control), cold control and hibernating golden hamsters. Sympathetic neurotransmission in the renal artery, the long term effects of hibernation on perivascular nerve activity, and the responsiveness of femoral artery to a number of neurotransmitters and hormones with both constrictor and dilator actions during hibernation are described.

The contractile responses of the renal arterial rings to transmural nerve stimulation (80 V, 0.1 ms, 4–64 Hz, for 1 s) were negligible in controls, significantly increased at higher frequencies of stimulation in cold controls and markedly enhanced in the hibernating group at all frequencies tested. The contractile responses to exogenous noradrenaline (NA; 0.1–100 μm) were significantly increased in the renal arteries of hibernating hamsters compared with controls, but not compared with cold controls. Responses to exogenous ATP (1–3000 μm) and KCl (120 mm) were similar among all experimental groups.

The maximal contractile responses of femoral arterial rings to the sympathetic co‐transmitter ATP and 5‐hydroxytryptamine were increased by approximately 124 % and 99 %, respectively, in hibernating compared with cold control preparations without a change in the concentration of agonist that produces half‐maximal response. However, the responses to NA were not altered during hibernation.

Vasoconstriction of femoral arterial rings in response to arginine vasopressin was significantly enhanced in both cold controls and hibernating groups, while vasoconstriction in response to endothelin‐1 and KCl was unaltered.

The dilator responses of femoral arterial rings to acetylcholine, sodium nitroprusside and adenosine were not different among the groups.

It is suggested that the marked augmentation of sympathetic neurotransmission, selective supersensitivity of the vascular smooth muscle to sympathetic contractile agents and unaltered vasodilatory mechanisms may provide a means for maintenance of vascular tone and peripheral resistance during hibernation.
Infant stepping: a method to study the sensory control of human walking
Authors: Yang Jaynie F. , Stephens Marilee J. , Vishram Rosie
Published: September 2004

Stepping responses were studied in infants between the ages of 10 days and 10 months while they were supported to step on a slowly moving treadmill belt. Surface electromyography (EMG) from muscles in the lower limb, force exerted by the feet on the treadmill belt, and the motion of the lower limbs were recorded.

Two groups of infants were studied, those who had a small amount of daily practice in stepping and those who did not. Practice resulted in a dramatic increase in the incidence of stepping recorded in the laboratory, particularly for the periods between 1 and 6 months of age.

The majority of infants showed clear alternation between the flexor and extensor muscles during walking, regardless of age. Co‐contraction between flexors and extensors, estimated by the overlap in area between rectified and smoothed EMG from a muscle pair, was greater for some muscle groups in the infant compared with the adult.

Practice resulted in a significantly lower co‐contraction index for the tibialis anterior‐ quadriceps muscle pair. Practice did not affect the mean step cycle duration.

Infants of all ages could step at a range of treadmill speeds by adjusting their step cycle duration. The relationship between the treadmill speed and cycle duration was well fitted by a power function, similar to those reported for intact cats and adult humans. The change in step cycle duration resulted almost entirely from a change in the extensor burst duration, whereas the flexor burst duration remained constant.

Airstepping could be elicited in some infants. The cycle durations for airstepping were close to the shortest cycles recorded on the treadmill.

In conclusion, the system for generating rhythmic, alternating activity of the lower limbs for stepping is clearly developed by birth. The stepping is sustained and regular, particularly if stepping practice is incorporated briefly each day. The infant population provides a good subject pool for studying the afferent control of walking in the human, before cerebral influences are fully developed. The characteristics and maturity of the system remain to be determined.
Glycolysis is independent of oxygenation state in stimulated human skeletal muscle in vivo
Authors: Conley Kevin E. , Kushmerick Martin J. , Jubrias Sharon A.
Published: September 2004

We tested the hypothesis that the cytoplasmic control mechanism for glycolysis is affected by the presence of oxygen during exercise. We used a comparison of maximal twitch stimulation under ischaemic and intact circulation in human wrist flexor and ankle dorsiflexor muscles. 31P magnetic resonance spectroscopy followed the phosphocreatine (PCr), Pi and pH dynamics at 6–9 s intervals. Glycolytic PCr synthesis was determined during stimulation from pH and tissue buffer capacity, as well as the oxidative phosphorylation rate.

Ischaemic vs. aerobic stimulation resulted in similar glycolytic fluxes in the two muscles. The onset of glycolysis occured after fifty to seventy stimulations and the extent of glycolytic PCr synthesis was directly proportional to the number of stimulations thereafter.

Two‐fold differences in the putative feedback regulators of glycolysis, [Pi] and [ADP], were found between aerobic and ischaemic stimulation. The similar glycolytic fluxes in the face of these differences in metabolite levels eliminates feedback as a control mechanism in glycolysis.

These results demonstrate that glycolytic flux is independent of oxygenation state and metabolic feedback, but proportional to muscle activation. These results show a key role for muscle stimulation in the activation and maintenance of glycolysis. Further, this glycolytic control mechanism is independent of the feedback control mechanism that governs oxidative phosphorylation.
Changes in Achilles tendon moment arm from rest to maximum isometric plantarflexion: in vivo observations in man
Authors: Maganaris Constantinos N. , Baltzopoulos Vasilios , Sargeant Anthony J.
Published: September 2004

The purpose of the present study was to examine the effect of a plantarflexor maximum voluntary contraction (MVC) on Achilles tendon moment arm length.

Sagittal magnetic resonance (MR) images of the right ankle were taken in six subjects both at rest and during a plantarflexor MVC in the supine position at a knee angle of 90 deg and at ankle angles of ‐30 deg (dorsiflexed direction), ‐15 deg, 0 deg (neutral ankle position), +15 deg (plantarflexed direction), +30 deg and +45 deg. A system of mechanical stops, support triangles and velcro straps was used to secure the subject in the above positions. Location of a moving centre of rotation was calculated for ankle rotations from ‐30 to 0 deg, ‐15 to +15 deg, 0 to +30 deg and +15 to +45 deg. All instant centres of rotation were calculated both at rest and during MVC. Achilles tendon moment arms were measured at ankle angles of ‐15, 0, +15 and +30 deg.

At any given ankle angle, Achilles tendon moment arm length during MVC increased by 1‐1.5 cm (22‐27 %, P < 0.01) compared with rest. This was attributed to a displacement of both Achilles tendon by 0.6‐1.1 cm (P < 0.01) and all instant centres of rotation by about 0.3 cm (P < 0.05) away from their corresponding resting positions.

The findings of this study have important implications for estimating loads in the musculoskeletal system. Substantially unrealistic Achilles tendon forces and moments generated around the ankle joint during a plantarflexor MVC would be calculated using resting Achilles tendon moment arm measurements.
Determination of both the time constant of v̇O2 and Δv̇O2/ΔW from a single incremental exercise test: validation and repeatability
Authors: Wisén Anita G. M. , Wohlfart Björn
Published: September 2004

A single incremental cycle exercise test including a steady‐state load, combined with respiratory gas exchange, was performed with the objective of determining the time constant (o2) and the amount of oxygen required at each load (o2/ΔW) by using a novel equation. The protocol was validated using four exercise tests at different constant loads and conventionally fitted mono‐exponential functions to determine o2, and interpolation of o2 versus load to determine o2/ΔW. No significant differences were seen between the means of either o2 or o2/ΔW determined with the two protocols. The correlation coefficient was 0·62 for o2 and 0·48 for o2/ΔW. The absolute differences (2 SD) were 11·6 s for o2 and 1·1 ml min−1 W−1 for o2/ΔW. The equations were compared in the same steady‐state test and good agreement of o2 was obtained (R = 0·99). The 5–6‐week repeatability (incremental test) was evaluated. No statistical differences were seen between the mean of the repeated tests. The difference between the tests (2 SD) were 20 s for o2 and 1·2 ml min−1 W−1 for o2/ΔW. In conclusion, o2 and o2/ΔW can be determined from a single incremental test. The validation showed an acceptable agreement, although the variations in absolute values were not negligible. This could partly be explained by the natural day‐to‐day variation and fluctuations in incoming raw data. The test–retest variation in absolute values was considerable, which must be taken into account when using o2 and o2/ΔW for evaluation of aerobic function.
Microvascular response in guinea pig skin to histamine challenge with and without application of skin window
Authors: Evilevitch Vladimir , Norrgren Kristina , Greiff Lennart , Wollmer Per
Published: September 2004

We measured the microvascular response to histamine in guinea pig skin. Histamine (40 mg ml−1) was given either as a skin prick test or applied topically onto a skin window. The skin window was prepared by applying suction and gentle warming to the skin so that a blister was formed, and by removing the top of the blister. The microvascular response was measured as the accumulation of radiolabelled transferrin in the skin in vivo, reflecting a combination plasma exudation and vasodilatation. In the control (saline) challenge, the response was slightly greater in the skin window than after skin prick challenge and the scatter was larger. Histamine challenge resulted in a significant microvascular response with respect to the control situation when measured immediately after provocation for both challenge techniques. Ten minutes after challenge, a smaller response was measured, which was still significantly greater than control for the skin prick challenge, but not for topical provocation using the skin window technique. We conclude that the microvascular response to histamine after provocation with the skin prick technique is similar to that after topical provocation using the skin window technique. The skin window technique may have a lower sensitivity than the skin prick technique owing to a higher scatter in the control situation. This difference should be considered when performing and interpreting studies of the microvascular reaction in the skin.
Chronotropic incompetence to exercise separates low body weight from established anorexia nervosa
Authors: Roche Frédéric , Barthélémy Jean‐Claude , Garet Martin , Costes Frédéric , Pichot Vincent , Duverney David , Kadem Myriam , Millot Luc , Estour Bruno
Published: September 2004

Chronotropic incompetence (CI), characterized by an attenuated heart rate (HR) response to exercise could participate to the limitation of exercise capacity in anorexia nervosa (AN). Therefore, we evaluated the role of cardiac sympathetic responsiveness in AN patients. In addition, the ambulatory value of autonomic control using spectral analysis of heart rate variability (HRV) was determined and correlated to maximal exercise performance. Twenty‐two patients hospitalized for weight loss and suspicion of AN were included in the study. All performed a symptom‐limited exercise test with measurement of gas exchange for chronotropic response to exercise evaluation. Holter ECG recordings allowed daytime and night‐time spectral domain HRV analysis in order to evaluate the alteration of sympathetic control of HR in free‐living conditions. CI defined as a failure to achieve 80% of heart rate reserve (%HRR) was observed in 13 (59%) patients (CI+). This group presented a higher body mass deficit than the group without CI (CI−; −35·1 ± 8·7% versus −26·1 ± 10·7%; P<0·05). Obviously, patients with a lower body mass index (BMI < 16 kg m−2, n = 14) revealed a more severe limitation to maximal exercise with a lower peak HR, a lower peak Vo2, and a lower maximal O2 pulse (P<0·05). BMI was significantly correlated to peak Vo2, maximal HR, and %HRR achieved at peak exercise. Daytime HRV parameters reflecting the sympathetic autonomic equilibrium (LF nu, LF/HF ratio) were significantly lower in CI+ patients. Blunted sympathetic response to maximal exercise is frequent and correlated to weight deficit. The present data suggest a major autonomic derangement in AN characterized by a cardiac sympathetic withdrawal.
Myocardial velocities measured during adenosine, dobutamine and supine bicycle exercise: a tissue Doppler study in healthy volunteers
Authors: Saha Samir K. , Brodin Lars‐Åke , Lind Britta , Svedenhag Jan , Strååt Eva , Gunnes Sigurd
Published: September 2004

Background:  Dobutamine stress echocardiography (DSE) quantified by tissue Doppler (TVI) have improved the diagnostic capacity of the procedure. Quantification of other stress modalities, e.g. adenosine stress echo (ASE) and exercise stress echocardiography (ESE) are necessary for assessing any pathophysiological differences in different forms of stress.

Methods:  Ten healthy individuals underwent ASE, DSE, and ESE during a span of 2–5 days. Left ventricular (LV) apical images at rest and peak stress (max) were postprocessed using TVI on a GE System FiVe equipment. ECG‐derived QRS duration (QRSD, ms), heart rate (HR, bpm), TVI‐estimated basal systolic velocities (S2V, cm s−1), ejection time (S2T, ms) and strain (S, %) were computed off‐line and compared. Longitudinal displacement imaging, tissue tracking, was also made.

Results:  Data for ASE, DSE and ESE during peak stress were (HR: 84 ± 12***, 142 ± 19, 137 ± 27; P<0·001) (QRSD: 92 ± 18**, 74 ± 13, 79 ± 9; P<0·05), (S2T: 307 ± 34***, 175 ± 53, 192 ± 25; P<0·001) and (S%: 26·0 ± 3·0, 21·2 ± 7·3, 22·1 ± 5·1; P = n.s.) respectively. Velocity response, registered in the LV septum at max, was lowest during ASE (7·4 ± 1·4) highest during DSE (13·0 ± 2·7; P<0·001 versus ASE) and somewhat intermediate during ESE (11·3 ± 3·5; P<0·001 versus ASE). In contrast, strain and displacement did not differ.

Conclusion:  ASE evokes significantly less LV systolic response compared with both DSE and ESE. Increased velocity (P<0·05 versus rest) and strain (P>0·05) response at a much lower HR indicates that adenosine has minor effects on contraction presumably secondary to vasodilatation. Powerful chronotropic response to DSE and ESE is probably prerequisite for strong velocity response at the expense of strain and displacement. TVI‐assisted stress echocardiography thereby shows different LV systolic response in healthy individuals, depending on stress modality.
Determination of the left ventricular long‐axis orientation from a single short‐axis MR image: relation to BMI and age
Authors: Engblom Henrik , Hedström Erik , Palmer John , Wagner Galen S. , Arheden Håkan
Published: September 2004

Accurate determination of imaging planes in relation to the left ventricular (LV) long‐axis orientation is important for anatomical and functional evaluation as well as for serial comparisons with cardiac magnetic resonance (CMR) imaging. Therefore, a fast and reliable method to test the accuracy of CMR imaging for measuring the orientation of the LV long‐axis was developed and validated. In addition, the relationship between LV long‐axis orientation and body mass index (BMI), gender and age was assessed. Two approaches were used, a long‐axis approach (based on a manually defined vector) and a short‐axis approach (based on a calculated vector). The concordance between the two approaches was assessed in 72 healthy volunteers. The accuracy and precision of MR imaging for measuring three‐dimensional orientations were tested using a LV phantom. The mean difference between the long‐ and short‐axis approaches for measuring the LV long‐axis orientation in the study population was 0 ± 3°, 0 ± 2°, and −1 ± 3° in the frontal, transverse and sagittal plane, respectively. BMI and age were shown to influence LV long‐axis orientation, especially in the frontal and sagittal planes. A significant difference in LV long‐axis orientation in the frontal and sagittal planes was found between genders. The correlation coefficient between MR‐measured phantom orientation and true phantom orientation was >0·98 in all three orthogonal planes. These observations suggest that a single LV short‐axis MR image can be used for measuring LV long‐axis orientation in patients with no cardiac disease.
Prevalence and Diagnosis of Migraine in Patients Consulting Their Physician With a Complaint of Headache: Data From the Landmark Study
Authors: Tepper Stewart J. , Dahlöf Carl G.H. , Dowson Andrew , Newman Lawrence , Mansbach Hank , Jones Martin , Pham Ba , Webster Chris , Salonen Reijo
Published: September 2004

Context.—Headache experts have suggested that to improve the recognition of migraine, patients with a stable pattern of episodic, disabling headache and a normal physical exam should be considered to have migraine in the absence of contradictory evidence. The premise upon which this approach is based—that is, that episodic, recurrent primary headache in the clinic is usually migraine—has not been evaluated in prospective clinical studies.

Objectives.—To (1) evaluate the diagnoses of patients consulting their physician with primary episodic headache and (2) compare clinic diagnoses and patient self‐diagnoses with International Headache Society (IHS) headache diagnoses assigned on the basis of longitudinal data from patient diaries.

Design.—Prospective, open‐label study. During the screening visit, patients self‐reported a headache diagnosis and then were assigned a headache diagnosis by their physician following his or her customary practice. Patients with a new physician diagnosis of migraine or nonmigraine primary headache were given diaries to record headache symptoms for up to 3 months or 6 attacks. Members of an expert panel, unaware of the clinic diagnosis, used diary data to assign a headache diagnosis to each attack and to each patient.

Setting.—One hundred twenty‐eight (128) practices in 15 countries including the United States.

Patients.—A total of 1203 male and female patients between 18 and 65 years of age who consulted their physician with headache as a primary or secondary complaint.

Results.—Overall, 94% of patients with a physician diagnosis of nonmigraine primary headache or a new clinic diagnosis of migraine had IHS‐defined migraine (76%) or probable migraine (migrainous) (18%) headache on the basis of longitudinal diary data. A new clinic diagnosis of migraine was almost always correct: 98% of patients with a clinic diagnosis of migraine had IHS‐defined migraine (87% of patients) or probable migraine (11% of patients) headache on the basis of longitudinal diary data. On the other hand, review of diaries of patients with a clinic diagnosis of nonmigraine revealed that 82% of these patients had IHS‐defined migraine (48%) or probable migraine (34%) headache. Altogether, one in four patients (25%) with IHS‐defined migraine according to longitudinal diary data did not receive a clinic diagnosis of migraine.

Conclusions.—These findings support the diagnostic approach of considering episodic, disabling primary headaches with an otherwise normal physical exam to be migraine in the absence of contradictory evidence. If in doubt of diagnosis or when assigning a nonmigraine diagnosis, strong consideration should be given to the use of a diary to confirm primary headache diagnosis.
A Combination of Riboflavin, Magnesium, and Feverfew for Migraine Prophylaxis: A Randomized Trial
Authors: Maizels Morris , Blumenfeld Andrew , Burchette Raoul
Published: September 2004

Objective.—To determine the efficacy for migraine prophylaxis of a compound containing a combination of riboflavin, magnesium, and feverfew.

Background.—Previous studies of magnesium and feverfew for migraine prophylaxis have found conflicting results, and there has been only a single placebo‐controlled trial of riboflavin.

Design/Methods.—Randomized double‐blind placebo‐controlled trial of a compound providing a daily dose of riboflavin 400 mg, magnesium 300 mg, and feverfew 100 mg. The placebo contained 25 mg riboflavin. The study included a 1‐month run‐in phase and 3‐month trial. The protocol allowed for 120 patients to be randomized, with a preplanned interim analysis of the data after 48 patients had completed the trial.

Results.—Forty‐nine patients completed the 3‐month trial. For the primary outcome measure, a 50% or greater reduction in migraines, there was no difference between active and “placebo” groups, achieved by 10 (42%) and 11 (44%), respectively (P= .87). Similarly, there was no significant difference in secondary outcome measures, for active versus placebo groups, respectively: 50% or greater reduction in migraine days (33% and 40%, P= .63); or change in mean number of migraines, migraine days, migraine index, or triptan doses. Compared to baseline, however, both groups showed a significant reduction in number of migraines, migraine days, and migraine index. This effect exceeds that reported for placebo agents in previous migraine trials.

Conclusion.—Riboflavin 25 mg showed an effect comparable to a combination of riboflavin 400 mg, magnesium 300 mg, and feverfew 100 mg. The placebo response exceeds that reported for any other placebo in trials of migraine prophylaxis, and suggests that riboflavin 25 mg may be an active comparator. There is at present conflicting scientific evidence with regard to the efficacy of these compounds for migraine prophylaxis.
Rizatriptan 5 mg for the Acute Treatment of Migraine in Adolescents: Results From a Double‐Blind, Single‐Attack Study and Two Open‐Label, Multiple‐Attack Studies
Authors: Hester Visser W. , Winner Paul , Strohmaier Kim , Klipfel Meghan , Peng Yahong , McCarroll Kathleen , Cady Roger , Lewis Donald , Nett Robert ,   on behalf of the Rizatriptan Protocol 059 and 061 Study Groups
Published: September 2004

Objective.—To examine the short‐ and long‐term efficacy and tolerability of rizatriptan 5 mg in adolescents with migraine.

Methods.—Two studies were conducted in patients aged 12 to 17 years. The first study was a randomized, double‐blind, placebo‐controlled, single‐attack study followed by a randomized, 1‐year, open‐label extension. The second study was a randomized, 1‐year, open‐label study. In the single‐attack study, patients treated a moderate or severe migraine headache and up to two recurrences with rizatriptan 5‐mg tablets (n = 234) or placebo (n = 242). Patients were instructed to use the study medication only on nonschool days. Headache severity, associated symptoms, and functional disability were assessed by the patient at 0.5, 1, 1.5, 2, 3, and 4 hours after the initial dose. In the 1‐year studies, patients treated up to 6 migraine attacks per month with rizatriptan 5‐mg tablets (n = 273), rizatriptan 5‐mg wafers (n = 281), or standard care therapy (n = 132). Headache severity was assessed by the patient at 2 hours after the initial dose. In all studies, the primary efficacy measure was pain relief at 2 hours post dose.

Results.—In the single‐attack study, the proportion of patients with pain relief at 2 hours was not significantly different between rizatriptan 5 mg (68.2%) and placebo (68.8%). Fewer patients than expected (about 30%) treated their migraine attacks on the weekend. Among these patients, the proportion with pain relief at 2 hours was significantly higher in the rizatriptan group than in the placebo group (74% vs. 58%, P = 0.022). In the multiple‐attack studies, pain relief at 2 hours was achieved in significantly more attacks treated with rizatriptan 5‐mg tablet (77%) or with rizatriptan 5‐mg wafer (77%) than with standard care (64%). Rizatriptan 5 mg was well tolerated in both the studies, with an adverse event profile not significantly different from that of placebo or standard care.

Conclusions.—Rizatriptan 5 mg was not more effective than placebo in the treatment of a single migraine attack in adolescents, but appeared to be more effective than standard care for treating multiple attacks occurring over 1 year in these patients. Rizatriptan 5 mg was well tolerated in adolescents during short‐term and long‐term use.
Migraine Treatment With Rizatriptan and Non‐Triptan Usual Care Medications: A Pharmacy‐Based Study
Authors: Cady Roger , Martin Vincent , Adelman James , Diamond Merle , Sajjan Shiva , Henry Hu X.
Published: September 2004

Objective.—To compare the effectiveness of rizatriptan to other non‐triptan medications in the relief of migraine headache in usual care settings.

Background.—Although rizatriptan has been shown to provide effective relief of migraine symptoms in clinical trials, limited data exist directly comparing its effectiveness with non‐triptan medications.

Methods.—Migraineurs aged 18 to 55 who had been prescribed a new antimigraine drug (rizatriptan 10 mg or a selected class of non‐triptan oral medications) were recruited to participate in the study through a national retail pharmacy chain. Participants completed a baseline questionnaire at the enrollment and reported their treatment experiences by filling out the treatment diary after using the newly prescribed medication. The treatment outcomes of patients receiving rizatriptan were compared with those receiving non‐triptan medications. Logistic regression analysis was applied to test statistical significance with adjustment for potential confounding factors.

Results.—Of the 728 patients who entered the study, 693 (95.2%) completed the treatment diary. Patients treated with rizatriptan (192) and non‐triptans (501) reported the following outcomes, respectively—onset of headache relief within 30 minutes post‐dose: 25% versus 18%; self‐defined significant headache relief within 2 hours post‐dose: 71% versus 54%; pain free or mild pain at 2 hours post‐dose: 58% versus 47%; completely symptom‐free within 2 hours of post‐dose: 32% versus 20%; return to usual activities within 2 hours post‐dose: 39% versus 35%; and satisfied with treatment: 67% versus 55% (P < .05 in all comparisons with exception of returning to usual activities).

Conclusion.—Rizatriptan was significantly more effective than non‐triptans in the relief of migraine headaches for patients obtaining prescribed migraine medications from a retail pharmacy. Additional studies at other usual care settings may be needed to confirm the findings.
Unilateral Black Hairy Tongue in Trigeminal Neuralgia
Authors: Cheshire William P.
Published: September 2004

Unilateral hairlike discoloration of the tongue is described in a patient with ipsilateral mandibular division trigeminal neuralgia. This unusual physical sign coincided with the patient's painful trigger zone and was attributed to hypertrophy of keratinized filiform papillae, where guarded avoidance of mechanical stimulation over time prevented normal desquamation.
Familial Hemiplegic Migraine, Neuropsychiatric Symptoms, and Erdheim‐Chester Disease
Authors: Black David F. , Kung Simon , Sola Christopher L. , Bostwick Michael J. , Swanson Jerry W.
Published: September 2004

We report the occurrence of unilateral cerebral hemisphere edema with subsequent cortical laminar necrosis in the setting of familial hemiplegic migraine (FHM) and permanent neurologic sequelae after resolution of an attack in 1 patient. Contemporaneous with this severe attack of FHM, the patient was found to exhibit multiple systemic and neurological symptoms referable to Erdheim‐Chester disease (a rare non‐Langerhans cell histiocytosis) that was confirmed by bone biopsy. This case demonstrates the severity possible with a migrainous infarction associated with FHM. The co‐occurrence of two such rare entities in 1 patient suggests a possible relationship.
Headaches and Pineal Cyst: A (More Than) Coincidental Relationship?
Authors: Peres Mario F.P. , Zukerman Eliova , Porto Pedro P. , Brandt Reynaldo A.
Published: September 2004

Pineal cysts are common findings in neuroimaging studies. The cysts are more frequent in women in their third decade of life. Pineal cysts can be symptomatic, headache is the most common symptom. The pineal gland has important physiological implications in humans, but little is known about the impact of pineal cysts in human physiology. We report 5 headache patients with pineal cyst, 4 women, 1 man, mean age 37.6, mean cyst diameter 10.1 mm. Two patients had migraine without aura, 1 migraine with aura, 1 chronic migraine, and 1 hemicrania continua. Three patients had strictly unilateral headaches. We hypothesize pineal cysts may be not incidental in headache patients, inducing an abnormal melatonin secretion.
Carotid Artery Dissection in Ergotamine Abuse
Authors: Akova‐Öztürk Esra , Husstedt Ingo W. , Ringelstein E. Bernd , Evers Stefan
Published: September 2004

The case of a 65‐year‐old male migraine patient with spontaneous internal carotid artery dissection is presented. He had been abusing ergotamine compounds for several years on at least 15 days per month. A possible association between arterial dissection and ergotamine abuse is discussed.
Role of platelet surface glycoprotein Ibα and P‐selectin in the clearance of transfused platelet concentrates
Authors: Leytin Valery , Allen David J. , Gwozdz Adam , Garvey Bernadette , Freedman John
Published: September 2004

BACKGROUND:  Role of P‐selectin (CD62) and glycoprotein (GP) Ibα in posttransfusion clearance of platelet concentrates (PCs) is unclear.

STUDY DESIGN AND METHODS:  Platelet (PLT) activation in vitro was determined by flow cytometry using anti‐CD62 and anti‐GPIbα. PC clearance in vivo was evaluated in an animal model using rabbits with an inhibited reticuloendothelial system, as measured by 0.5‐hour (R0.5), 24‐hour (R24), and total (R∑) PLT recoveries, and survival time (ST). Correlations were analyzed between in vitro assays of PLT activation and in vivo clearance of conventional (Days 2‐5), outdated (Days 7‐8), and refrigerated PCs.

RESULTS:  Binding of anti‐CD62 to the PLT surface was significantly increased and of anti‐GPIbα decreased in outdated and refrigerated PCs compared to conventional PCs. Negative correlation was observed between in vitro anti‐CD62 binding and the fast (R0.5) PLT clearance, but not with delayed (R24 and ST) clearance. In contrast, anti‐GPIbα binding showed positive correlations with delayed but not with fast PLT clearance. Overall (R∑) clearance correlated better with anti‐GPIbα than with anti‐CD62 binding. CD62 density on the PLT surface was decreased after PC transfusion, whereas GPIbα density remained unchanged.

CONCLUSION:  These data suggest that CD62 exposure on the PLT surface during PC storage triggers fast CD62‐mediated PC clearance, whereas in vitro GPIbα changes are involved in delayed GPIbα‐mediated PC clearance.
Iron supplementation and 2‐unit red blood cell apheresis: a randomized, double‐blind, placebo‐controlled study
Authors: Radtke Hartmut , Mayer Beate , Röcker Lothar , Salama Abdulgabar , Kiesewetter Holger
Published: September 2004

BACKGROUND:  The benefits of 2‐unit red blood cell (RBC) apheresis are evident, but iron depletion may be a limiting factor in using this technology. Regular iron supplementation may allow a better utilization of this technique.

STUDY DESIGN AND METHODS:  In this study, 260 regular blood donors donated 2‐unit RBCs on each of a total of seven visits at intervals of 8 to 10 weeks. The volunteers were randomly assigned to receive 100 mg of iron(II) or placebo daily. Group A received iron capsules after the first three donations, and Group B after the second three donations, respectively. Hemoglobin, serum ferritin, and serum iron were measured before each donation.

RESULTS:  Mean serum ferritin concentration decreased after each donation in the placebo phase of both treatment groups, but it remained largely constant during the iron phase in Group A, and even increased during the iron phase in Group B.

CONCLUSION:  Regular iron supplementation prevents iron depletion in the majority of donors after 2‐unit RBC apheresis within an 8‐ to 10‐week period.
A mathematical model of cell salvage compared and combined with normovolemic hemodilution
Authors: Waters Jonathan H. , Lee Julia Shin Jung , Karafa Matthew T.
Published: September 2004

BACKGROUND:  Mathematical models have been used to describe the factors that affect cell salvage (CS) and normovolemic hemodilution (ANH). Here, the CS and ANH models were used to compare these two techniques alone or in combination with each other.

STUDY DESIGN AND METHODS:  Variables used for a hypothetical patient included an estimated blood volume of 5000 mL, a presurgery hematocrit (Hct) of 45 percent, and a transfusion trigger of 21 percent. The model accounts for both the effect of decreasing the Hct due to blood loss and the effect of increasing Hct due to the readministration of blood in an isovolemic patient. The efficacy of CS and ANH is defined to be the maximum allowable blood loss for a fixed blood volume and a fixed transfusion trigger.

RESULTS:  Comparison of CS with ANH showed that 3 units of ANH was comparable to CS when CS recovery rates ranged from 19 to 24 percent. For a patient with a blood volume of 5000 mL and a starting Hct of 40 percent, 3 units of ANH would allow for 3972 mL of blood to be lost before crossing a 21‐percent transfusion trigger, whereas CS with a 125‐mL bowl would allow for 7611 mL.

CONCLUSION:  When comparing ANH to CS, this mathematical model would suggest that CS has the potential to offer significantly greater red blood cell avoidance than does ANH; however, the combination of ANH with CS may offer allogeneic avoidance superior to either technique alone.
Acute lung injury after blood transfusion in mechanically ventilated patients
Authors: Gajic Ognjen , Rana Rimki , Mendez Jose L. , Rickman Otis B. , Lymp James F. , Hubmayr Rolf D. , Moore S. Breanndan
Published: September 2004

BACKGROUND:  Liberal transfusion strategy increases the risk of acute lung injury (ALI), but specific transfusion‐related factors have not been characterized. We tested the hypotheses that storage age and specific type of blood products are associated with increased risk of ALI in mechanically ventilated patients.

STUDY DESIGN AND METHODS:  From a database of mechanically ventilated patients, we identified those who received blood products during the first 48 hours of intensive care. We extracted information about underlying ALI risk factors as well as the type, amount, and shelf age of administered blood products. Outcome was assessed by an independent, blind review of chest radiographs and clinical findings.

RESULTS:  Of 181 patients transfused during the first 48 hours of mechanical ventilation, 60 (33%) developed ALI. There was no difference in average duration of red blood cells storage between patients who did and did not develop ALI (median, 18.5 vs. 17.5 days; p = 0.22). In a multivariable logistic regression analysis, important risk factors associated with the development of ALI were thrombocytopenia (odds ratio, 5.9; p = 0.004) and transfusion of fresh frozen plasma (odds ratio, 3.2; p = 0.023).

CONCLUSION:  Thrombocytopenia and transfusion of fresh frozen plasma, but not storage age of red blood cells, were associated with the development of ALI in this cohort of mechanically ventilated patients.