bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiovascular Reflexes and Plasma Noradrenaline Levels in Migraine Patients Before and During Nimodipine Medication
Authors: Havanka‐Kanniainen H. , Juujärvi K. , Tolonen U. , Myllylä V.V.
Published: June 2005

SYNOPSIS

In twenty‐one migraine patients, cardiovascular reflex responses and noradrenaline (NA) levels were measured before and after four weeks of calcium antagonist nimodipine medication. Nineteen healthy subjects served as a control group for cardiovascular reflex responses and ten of them as a control group for noradrenaline levels.

Neither the cardiovascular reflexes nor the noradrenaline levels differed significantly when the values before and after four weeks of nimodipine medication were compared with each other.

The mean pulse rate reaction connected with both normal and deep breathing differed significantly when the results of migraine patients and controls were compared with each other, this result suggesting subtle parasympathetic hypofunction in migraine patients. When the mean Valsalva ratios and the mean postural pulse rate reaction ratios were compared, the ratios in migraine patients were significantly lower than in control subjects (p<0.025), suggesting sympathetic hypofunction in migraine patients. The mean diastolic blood pressure rise in migraineurs in the isometric work test was 15.2 ± 9.4 and in controls 24.0 ± 9.4 (p<0.001). The baseline levels of the NA determinations did not differ when the values of migraineurs and controls were compared with each other; but after 3 minutes of standing, the rise in NA levels in migraine patients was significantly lower than in controls (p<0.05). These results suggest sympathetic hypofunction in migraineurs.
The Effect of Intravenous Verapamil on Acute Migraine Headache
Authors: Molaie Majid , Olson Carin M. , Koch John
Published: June 2005

SYNOPSIS

We conducted a double blind placebo controlled study on the effect of intravenous injection of verapamil in 12 patients with acute migraine headache who sought medical help in the emergency room. Changes in the intensity of headache were scored every 10 minutes up to one hour following administration of 10 mg of Verapamil or placebo.

After infusion of placebo, one patient reported complete improvement, one had moderate improvement, and three had no improvement. Of those receiving verapamil, two reported moderate improvement, two had no improvement, and three were worse.

Our results indicate no beneficial effect of intravenous verapamil injection on acute migraine headache in progress.
Serendipity and Food Sensitivity: A Case Study
Authors: Gettis Alan
Published: June 2005

SYNOPSIS

The subject was a common‐migraine sufferer for many years. He kept detailed records regarding the frequency of his headaches and medication taken. An aspirin‐induced gastrointestinal bleed caused him to begin a bland oligoantigenic diet. He became headache‐free shortly thereafter. Single food challenges, done carefully and deliberately, revealed sensitivities to banana, citrus, and cheese, all foods containing potent vasoactive amines. The year prior to his serendipitous discovery, the subject had headache on 326 days and took 1316 aspirin tablets. The year following it, in which he eliminated offending foods, he had headache on 8 days and took 16 tablets. Seven years of headache data are presented. Delayed reactions to foods, and multiple food sensitivities, may pose diagnostic problems. Headaches can occur up to 72 hours following ingestion of provoking foods. Oligoantigenic diets and single food challenges utilizing enough time so as to recognize delayed reactions are useful in detecting food sensitivities.
Nimodipine versus Flunarizine in Common Migraine: A Controlled Pilot Trial
Authors: Bussone G. , Baldini S. , D'Andrea G. , Cananzi A. , Frediani F. , Caresia L. , Milone F. Ferro , Boiardi A.
Published: June 2005

SYNOPSIS

The effects of Nimodipine and Flunarizine, both calcium‐antagonist drugs, in the prevention of common migraine were investigated in a double‐blind randomized parallel study. Five patients of the 30 included in the study dropped out because of adverse reactions. Two were treated with Nimodipine and three with Flunarizine. Our results suggest a similar efficacy for both drugs, although Nimodipine seems to have a shorter latency of effect. Nimodipine is a useful new agent for common migraine prevention.
EEG Features in Basilar Artery Migraine
Authors: Jacome Daniel E.
Published: June 2005

SYNOPSIS

Standard and 24‐hour ambulatory cassette electroencephalograms (EEG) were performed in 51 female patients with basilar artery migraine (BAM). None of the patients were known epileptics. The group age average was 29 years. Anomalies were detected in 9 patients (17.6%) Two exhibited paroxysmal specific (i.e., epileptogenic) and 7 paroxysmal non‐specific abnormalities. Studies during the symptomatic period on 7 patients were normal, and in one adolescent photoparoxysmal discharges were present. Her headaches persisted despite the suppression of EEG photoparoxysmal activity with valproate and carbamazepine; conversely, she was clinically improved with propranolol. EEG abnormalities occurred in the minority of adults afflicted with BAM. The presence of ictal or interictal abnormalities is not an absolute indication for antiepileptic therapy although these agents may, occasionally, be efficacious in the treatment of migraine, independent of associated EEG disturbances.
Headache Classification and Factor Analysis with a Pediatric Population
Authors: Mindell Jodi A. , Andrasik Frank
Published: June 2005

SYNOPSIS

The “Headache Symptom Questionnaire‐Revised” was administered to 68 pediatric headache sufferers and their parents. The questionnaire as a brief assessment tool can accurately classify 66.2% of the child headache sufferers. This classification accuracy was found to be equivalent to the 67.2% diagnostic agreement between experienced diagnosticians utilizing clinical interviews. Factor analysis of the questionnaire revealed four factors‐one being related to muscle contraction headaches, two factors being of a vascular nature, and the fourth factor related to both migraine and muscle contraction headache. This investigation, which utilized a population whose headaches are thought to be in a more “pure” state, continues to lend support to traditional notions of headache etiology and diagnosis.
Transformed or Evolutive Migraine
Authors: Mathew Ninan T. , Reuveni Uri , Perez Francisco
Published: June 2005

SYNOPSIS

630 (39%) of 1600 patients seen in a Headache Clinic over a three year period had chronic daily headaches (CDH). In 78% of these CDH patients, the daily headaches evolved out of a prior history of episodic migraine; these patients we designate as having “transformed” or “evolutive” migraine. The other 12% had migraine headaches which were daily from the start.

Patients with transformed migraine, in contrast to those with daily headaches from the start, have a significantly higher incidence of positive family history of migraine, menstrual aggravation of migraine, identifiable trigger factors, associated G.I. and neurological symptoms, and early morning awakening with headache.

The CDH group in general over‐used symptomatic medication and exhibited abnormalities on behavioral scale testing. Withdrawal of daily symptomatic medication, institution of a low tyramine low caffeine diet, initiation of prophylactic anti‐migraine therapy, and biofeedback and behavioral therapy, gave worthwhile improvement in 76% of chronic daily headache patients.

Factors which promote “evolution” of migraine from intermittent to chronic daily occurrence are not well‐defined but may include medication abuse, medication withdrawal, and psychiatric disturbances.
Prior Physical and Sexual Abuse in Women with Chronic Headache: Clinical Correlates
Authors: Domino Julia V. , Haber Joel D.
Published: June 2005

SYNOPSIS

Physical and/or sexual abuse in women with chronic headache has never been addressed. This pilot study addressed differences in women with chronic headache who reported such a history, compared to a control group of women with chronic headache without a traumatic history. Thirty women were divided into two groups, based on self‐report of abuse, and all women given an MMPI as part of their assessment. Sixty‐six percent of women reported significant traumatic histories, with a mean of 8 years of abuse; headache pain developed after trauma in 100% of these cases. Abused women had shorter chronicity of headache but reported greater psycho‐social distress and significantly more headaches. Results lend support to a model of life stress etiologically involved in the development of headache. Variables related to personality prior to headache development may be more important than the chronicity determinant. Assessment and identification of abuse early in the cycle may prevent long‐term adjustment problems.
Differential Prevalence Rates for Headaches: A Function of Stress and Social Support?
Authors: Martin Paul R. , Nathan Paula R.
Published: June 2005

SYNOPSIS

A recent study reported a very high headache prevalence rate for psychology undergraduate students attending a North American University. Reported here are the results of administering the same questionnaire to 711 students enrolled in the first year undergraduate psychology program at the University of Western Australia. The two studies produced dramatically different findings. The prevalence of regular headaches was 2.6 to 3.6 times as high at the North American University compared to its Australian counterpart. The average headache experienced by students attending the North American University was significantly more intense and of longer duration than the average headache experienced by students attending the Australian University. The possible causes of the differential rates were discussed, and it was suggested that the explanation lay in differences in stressors and factors that mediate the stress response. Specifically, the higher prevalence of headaches at the North American University was attributed to a greater incidence of stressors (particularly examinations), and of relatively deficient social support systems.
Tests of Thyroid Function in Chronic Headache Patients
Authors: Amy Jonathan R.
Published: June 2005

SYNOPSIS

Chronic, poorly localized headaches have been reported to be a not uncommon presenting complaint in patients with hypothyroidism. A study was performed to test the hypothesis that TSH measurement and TRH stimulation testing would identify some patients with hypothyroidism presenting as headache. Twenty‐one patients were tested, and none were found to be hypothyroid by these two measures. Thyroid testing may still be useful where the headache is accompanied by other symptoms of hypothyroidism, however.
Efficacy, Side Effects and Tolerance Compared During Headache Treatment With Three Different Calcium Blockers
Authors: Jónsdóttir María , Meyer John Stirling , Rogers Robert L.
Published: June 2005

SYNOPSIS

Experiences gained in this laboratory during long‐term, separate prophylactic trials utilizing three different calcium channel blockers among patients with common migraine, classic migraine, mixed and chronic cluster headaches are reviewed. Nifedipine provided symptomatic improvement among 65% of patients with common migraine and among 77% of patients with classic migraine. Forty‐one percent of patients with mixed headache reported some relief of head pain. Sixty percent of patients with chronic cluster reported improved control of their headaches. Verapamil produced improved control of symptoms in 81% of patients with common migraine, 72% of those with classic, 67% of those with mixed and 79% of those with cluster. Nimodipine was reported to be beneficial among 84% of patients with common migraine, among 73% of those with classic migraine and among 53% with chronic cluster. Only 33% of patients treated with nimodipine for mixed headache reported improvement. Side effects were more common with nifedipine (71%) than with verapamil (41%) and were least common with nimodipine (20%). Tolerance developed in 42% of those treated with nifedipine and in 49% of those treated with verapamil. Development of tolerance with nimodipine was rare (4%). Each of these three calcium channel blockers showed different and specific therapeutic efficacies which differed according to the clinical classification of the different types of vascular head pain undergoing treatment.
Atenolol in Migraine Prophylaxis a Double‐blind Cross‐over Multicentre Study
Authors: Johannsson Valur , Nilsson Lars R. , Widelius Tommy , Jäverfalk Tommy , Hellman Peter , Åkesson Jan‐Åke , Olerud Bengt , Gustafsson CarI‐Lennart , Raak Anders , Sandahl Gun , Tilling Björn , Almkvist Göran , Troein Margareta
Published: June 2005

SYNOPSIS

The prophylactic anti‐migraine effect of atenolol was compared to placebo in a multicentre study on 63 patients with classical and/or common migraine. The study design was double‐blind cross‐over and patients were given atenolol 100 mg o.d. or matching placebo during a study treatment period of 24 weeks. The effect of atenolol was significantly better than that of placebo: integrated headache values were reduced in 70% of the patients (p = 0.004) and the proportion of days with headache was reduced in 59% of the patients (p = 0.010). Few side effects were reported with both atenolol and placebo. This study shows atenolol to be safe and effective in the prophylactic treatment of migraine.
Headache May Arise From Perturbation of Brain
Authors: Raskin Neil H. , Hosobuchi Yoshio , Lamb Sharon
Published: June 2005

SYNOPSIS

Ray and Wolff in a landmark study of human patients under local anesthesia, concluded that the brain was not sensitive to pain; however, at the time of their study, the anatomy and physiology of pain transmission and modulation were largely unknown and their stimulating electrodes were not implanted in the brainstem or thalamic cells or projections now known to be important to pain perception. We now report 15 patients, previously headache‐free, who underwent electrode implantation in the periaqueductal gray between 1977 and 1982 who immediately at implantation or in the few days subsequent to implantation reported severe continuous head pain usually with florid “migrainous” feature that persisted for 2 months to 10 years. Ten of these patients were treated with reserpine and all were dramatically responsive to it, but 8 patients rapidly became tolerant. Seven patients who were treated with dihydroergotamine rapidly became headache‐free; 2 of the 7 became tolerant quickly. One patient developed the “cough headache” syndrome after implantation, was responsive to indomethacin, the syndrome abating in 6 months. These data suggest that perturbation of brain may generate head pain.
Comparative Efficacy of Nadolol and Propranolol in the Management of Migraine
Authors: Sudilovsky A. , Elkind A.H. , Ryan R.E. , Saper J.R. , Stern M.A. , Meyer J.H.
Published: June 2005

SYNOPSIS

A multicenter randomized double‐blind study was conducted on 140 patients with classic and/or common migraine who received either nadolol (80 mg or 160 mg OD) or propranolol (80 mg bid). Admission into the 12‐week active treatment period required at least 3 attacks per month during a placebo lead‐in period. Abortive headache therapy was allowed at the patients' discretion, each keeping a diary of migraine attacks and use of medications. Clinical assessments were performed monthly.

Data from 42 patients were excluded from the evaluation of efficacy, mainly because of non‐adherence to protocol requirements. Drug efficacy evaluation in the remaining 98 patients was based on 4 separate migraine indices: frequency of attacks, intensity of attacks, days of pain, and need for relief medication, with success being defined as a reduction in an index of at least 50% relative to baseline. A successful response in at least I index was found in 48% of patients on nadolol 80 mg (p=NS vs propranolol 160 mg) and in 69% of the patients on nadolol 160 mg compared with 54% on propranolol 160 mg (p<0.05). Success in all 4 indices was found in 21% of patients on nadolol 80 mg (p=NS vs propranolol 160 mg) and in 41% of patients on 160 mg nadolol as compared to 15% on propranolol 160 mg (p<0.05).

Adverse reactions required discontinuation from therapy in 2 of 48 patients on nadolol 80 mg (4.1%), 2 of 47 patients on nadolol 160 mg (4.3%), and 4 of 44 patients on propranolol 160 mg (9.1%).

This study indicates that, in the prophylaxis of migraine, 80 mg of nadolol administered once daily is equivalent in efficacy and safety to propranolol 80 mg administered twice daily. Furthermore, nadolol given as a single daily dose of 160 mg is superior to an equal total daily dose of propranolol administered twice daily.
Aseptic Inflammatory Meningeal Reaction Manifesting as a Migrainous Syndrome
Authors: Stamboulis Eleftherios , Spengos Michael , Rombos Andonis , Haidemenos Alexandros
Published: June 2005

SYNOPSIS

A female aged 24 years, without any previous personal and family history of migraine, presented with migrainous attacks characterized by headache, dizziness and nausea, accompanied by sensory, motor, visual and aphasic disturbances. The duration of the attacks ranged from 10–30 minutes, except for one episode which was accompanied by confusion and excitation and which lasted for many hours. The attacks recurred for approximately 6 weeks during which the condition of the patient was excellent between attacks. The patient recovered completely and in two years of follow‐up has not had any further migrainous attacks. The C.S.F. showed a predominantly lymphocytic pleocytosis and increased protein. A “symptomatic” migraine condition stemming from an inflammatory reaction of the meninges is thus suggested.
Treatment of Complicated Migraine with Sublingual Nifedipine
Authors: Goldner Jonathan A. , Levitt Lawrence P.
Published: June 2005

SYNOPSIS

The term complicated migraine is used when the neurologic deficits in classic migraine are intense or alarmingly prolonged. Its manifestations are felt secondary to a vasoregulatory disorder of cerebral vessels. The calcium channel antagonists have been found efficacious in blocking cerebral vasospasm. A young girl presented with severe headache, aphasia and clinical symptoms suggesting complicated migraine. Her neurologic deficit cleared immediately after the administration of sublingual nifedipine. Nifedipine may prove useful in treatment of complicated migraine.
A Case of Hemiplegic Migraine Treated with Flunarizine
Authors: Tobita Muneshige , Hino Masatoshi , Ichikawa Nobumichi , Takase Sadao , Ogawa Akira
Published: June 2005

SYNOPSIS

A patient with hemiplegic migraine who was treated successfully with flunarizine is presented. A fifteen‐year‐old boy developed right hemiparesis during several migraine attacks. Regional cerebral blood flow (CBF) measurement using intravenously injected xenon 133 showed that the CBF was about 10‐15% lower in left fronto‐temporo‐parietal regions than that on the contra‐lateral side. After the treatment with flunarizine at a dose of 10 mg/day, he has been free of migraine attacks and hemiparesis disappeared. Regional CBF 1 month after treatment showed no decrease in any region of the brain. The findings indicate that flunarizine reversed the neurological deficits by increasing CBF by its vasodilating action.
Biofeedback and Relaxation Training: The Effect on Headache and Associated Symptoms
Authors: Smith Wendy B.
Published: June 2005

SYNOPSIS

Patients suffering with migraine and muscle contraction headaches were treated with EMG and thermal biofeedback and relaxation training. Three groups were formed: Patients whose last contact with the practice was 3–12, 13–24, or 25 or more months prior to the follow‐up study. Each group included patients who never attended biofeedback, who attended one session, two to six sessions, or seven or more sessions of biofeedback. A telephone questionnaire revealed that 86% of patients who attended seven or more sessions of biofeedback maintained a 75–100% reduction in headache frequency through time (25 or more months). Of these patients, 65.5% reported a reduction in associated symptoms. Only 31% of patients who never attended biofeedback reported a reduction in headache frequency. Only 16.3% of patients who never attended biofeedback reported a reduction in associated symptoms. The combination of biofeedback and relaxation training clearly results in a reduction of both headache experience as well as in associated symptoms.
Nerves and Vessels in the Pterygopalatine Fossa and Symptoms of Cluster Headache
Authors: Hardebo Jan Erik , Elner Åke
Published: June 2005

SYNOPSIS

The study evaluates the contribution of activated parasympathetic and sensory nerve fibres in the sphenopalatine ganglion area, and of vasodilation in surrounding vessels in this narrow region (pterygopalatine fossa), to the pain and signs of autonomic dysfunction seen during attacks of cluster headache. Agents with anesthetic and vasoconstrictor effects were applied nasally to reach this area. It was found that the anesthetic effect is the most important, both regarding pain and autonomic symptoms. The effectiveness was also evaluated: this treatment is useful to stop attacks of cluster headache, but the beneficial effect is less than that reported in previous studies.
Menstrual Migraine: New Biochemical and Psychological Aspects
Authors: Nattaro Giovanni , Aliais Gianni , Lorenzo Cristina De , Torre Eugenio , Ancona Mario , Benedetto Chiara , Massobrio Marco
Published: June 2005

SYNOPSIS

Eighteen patients suffering from true menstrual migraine and 11 control subjects were studied.

We evaluated in different phases of the menstrual cycle and during the migraine crisis the platelet sensitivity to prostacyclin (PSP) and the platelet content of 5‐HT. We also investigated both in basal conditions (follicular phase of the cycle) and during the migraine attack the levels of anxiety and depression. Some personality traits (psychoticism, extroversion and neuroticism) were also analyzed.

The trends observed in the two groups are significantly different for both PSP (p<0.02) and 5‐HT (p<0.01).

Our data suggest the hypothesis that a change in platelet homeostasis, mainly evident in the luteal and perimenstrual phases of the cycle, can play a remarkable role in menstrual migraine pathogenesis.

From the psychological point of view, these patients are normal, even if they are significantly less extroverted (p< 0.005), more anxious (p<O.05) and more depressed (p<0.05) than controls.

The clinical features and the cyclic unavoidable recurrence of the menstrual crisis could account for this particular psychological picture.
Prophylaxis of Migraine with Anionic Polyelectrolytes
Authors: Thonnard‐Neumann Ernst , Bigelow Llewellyn B.
Published: June 2005

SYNOPSIS

In previous studies on patients with migraine headaches we found that 50% had reduced concentrations of basophils and lymphocytes. Treatment with inhalations of heparin often restored these blood indices to normal and was accompanied by a reduction in migraine headache, We report here data on the long term treatment of 37 migraine patients with inhalations of heparin and with an oral semi‐synthetic heparinoid, Pentosan Polysulfate (PNP). 27 patients responded with a mean improvement in migraine index of 79% and as a group showed significant increases in basophil, total lymphocyte, and in particular T‐cell concentrations.

Ten patients whose migraine headaches were related to their menstrual cycles were relatively unresponsive to heparin or PNP. They had a general leukopenia, but basophils were within normal range.
Common Migraine: Criteria for Diagnosis
Authors: Solomon Seymour , Cappa Karen Guglielmo , Smith Charles R.
Published: June 2005

SYNOPSIS

Current definitions of common migraine are not specific and new criteria are needed. Our concept of common migraine was supported by comparing the features of 100 consecutive patients we diagnosed as common migraine, with past series. The features of our patients with common migraine were then compared with 100 cases of chronic daily headache, the only form of “tension headache” that can unequivocally be differentiated from migraine. The features that occurred significantly (P<0.001) more often in patients with common migraine than in those with chronic daily headache, were nausea, vomiting, unilateral site, throbbing quality, photophobia or phonophobia, increase with menstruation, and a family history of migraine. Criteria using these features, as well as other sets of criteria, were evaluated by retrospectively applying them to the patients diagnosed as having common migraine and chronic daily headache.
On the Origin of Head Pain
Authors: Raskin Neil H.
Published: June 2005

SYNOPSIS

Clinical, pharmacological and biochemical evidence converge upon perturbed serotonergic neurotransmission as a putative mechanism of headache. The evidence is reviewed, drawing upon the clinical examples of cerebral infarction, arteriovenous malformation, migraine and cluster headache. Ordinary, periodic headache may be the “noise” of serotonergic neurotransmission.
Pattern‐reversal Visual Evoked Potentials and EEG Correlations in Common Migraine Patients
Authors: Mariani Emilio , Moschini Vincenzo , Pastorino Giancarlo , Rizzi Franco , Severgnini Amelia , Tiengo Mario
Published: June 2005

SYNOPSIS

22 migraine patients, aged between 17 and 60 years (7 males and 15 females) were studied through the method of Visual Evoked Potentials (VEP). The control group consisted of an equal number of healthy subjects, comparable for age and sex. Correlations between the results obtained with VEP and those reported by traditional EEG methods were investigated. As found by other authors, VEP's did not point to any significant difference in common migraine as compared to a control group of healthy subject.

Unlike other authors we found the presence of mildly abnormal EEG elements in only 19% of patients.
Cardiac Murmurs Indicative of Aortic Valve Disease with Chronic and Excessive Intake of Ergotamine
Authors: Spierings Egilius L. H.
Published: June 2005

SYNOPSIS

Two patients are reported who developed cardiac murmurs indicative of aortic valve disease during chronic and excessive intake of ergotamine. Ergotamine is an antimigraine medication chemically related to methysergide of which endocardial fibrosis is a rare but well‐established side‐effect.
Sudden Headache Associated With Unilateral Asterixis
Authors: Alvarez‐Cermeño J.C. , Martinez‐Castrillo J.C. , Gobernado J.M.
Published: June 2005

SYNOPSIS

In a patient presenting with sudden headache and right unilateral asterixis, a computed tomography scan (CT) showed a left thalamic hematoma. This and other four similar cases reported previously, indicate that the acute development of headache and focal asterixis should alert the clinician to the possibility of an intracranial hemorrhage.
The Controlled Application of Cold and Heat by a New Device (Migra‐lief Apparatus) in the Treatment of Headache
Authors: Lance J.W.
Published: June 2005

SYNOPSIS

An apparatus which incorporates a cooling compartment encircling the head, extending down the neck, and a separate warming compartment applied to the vertex, was employed in 28 patients with recurrent headaches (20 with migraine, 7 with tension headaches, and I with cluster headaches) who had had inadequate relief from prophylactic and acute medications. This Migra‐lief apparatus reduced severity of headache in 15 of the migraine patients, 6 of the tension headache patients, and in the one cluster headache patient.
Autonomic Dysfunction in Migraine: A Survey of 188 Patients
Authors: Havanka‐Kanniainen H. , Tolonen U. , Myllylä V.V.
Published: June 2005

SYNOPSIS

Autonomic nervous system functions were studied in 188 patients with migraine during headache free intervals by measuring cardiovascular reflex responses. Eighty‐five healthy subjects served as a control group.

Pulse rate (R‐R‐ interval) variation in normal and deep breathing, during Valsalva manoeuvre and orthostatic test was diminished in migraine patients. Diastolic blood pressure rises in orthostatic test and isometric work test were lower than in the controls. The results of patients with classic and common migraine did not deviate from each other. The same was true for the results of the female and male patients.

The results of the patients with frequent migraine attacks (>4/month) showed more severe disturbance than those with infrequent attacks. Disturbances gradually developed with age, being minimal or totally lacking in young migraine patients. The results confirm the development of sympathetic and parasympathetic hypofunction in migraine patients during the course of the disorder.
A Diagnostic Test for Migraine Using the Visual Evoked Potential
Authors: Marsters J.B. , Good P.A. , Mortimer M.J.
Published: June 2005

SYNOPSIS

Traditionally the diagnosis of migraine has been made by clinical history, examination and investigation to exclude other ophthalmological and neurological diseases. To date there has been no simple objective test for the diagnosis of migraine on an individual basis. Patients were subjected to both flash and pattern light stimuli, and measurements were made from the resultant visual evoked potential (VEP) charted as a waveform. Calculations based on the parameters of the waveforms produced a Coefficient which correlated well with the medical diagnosis. This study demonstrates that electro‐diagnostic methods can be utilised to provide a fast, reliable and accurate diagnosis for migraine on an individual basis, and which will also differentiate between the Common and Classical varieties.
Visual Evoked Potential in Patients with Migraine
Authors: Raudino Francesco
Published: June 2005

SYNOPSIS

Using pattern reversal stimuli, visual evoked potentials (VEP) were measured between attacks in 40 (6 classic and 34 common) migraine sufferers, and in 20 control subjects. While there were no statistically significant differences between the groups in mean P wave latency or in mean P wave amplitude, there were some intriguing individual findings in some of the migraine patients. Nine had P wave latencies more than 2 SD above the control mean; 6 had more than 2 SD increases above control in P wave amplitude; 3 had simultaneous increases in both latencies and amplitudes. In almost all the cases with these unusual values, the tracing had been done close in time to a migraine attack.
Clinical Characterization of Patients with Chronic Tension Headache
Authors: Langemark Michael , Olesen Jes , Poulsen Dorte Loldrup , Bech Per
Published: June 2005

SYNOPSIS

One hundred and forty‐eight patients with tension headaches at least 10 days per month were studied prospectively with a standardized interview, neurological examination and evaluation of muscle tenderness and jaw movements. Patients with migraine attacks oftener than once per month were excluded. Ninety‐three had daily headache. Median age at onset was 23 yrs. (quartiles 15–23 yrs.). Half of the patients had headache predominating in one part of the head. In the other half, headache was diffuse or with changing pattern. Fifty‐eight reported migraine attacks 1–12 times per year; twenty‐seven of these did not remember onset, 15 initially had migraine later developing into chronic headache, and 16 started with tension headache and developed migraine attacks later in life. Photophobia was reported as frequently associated with tension headache (migraine attacks not included) in 13 percent, infrequently in 38 percent and absent in 49 percent. Corresponding figures for phonophobia were 7, 35 and 57 percent. Characteristics of chronic tension headache were similar in patients with and without migraine attacks. The components included in the usual indices of temporo‐mandibular joint dysfunction showed little mutual correlation. Pericranial tenderness scores were elevated compared to previously studied controls. Tenderness in paravertebral muscles was significantly correlated to pericranial tenderness, and patients indicating influence by environmental factors had the highest pericranial tenderness scores. The findings are suggestive of a generalized muscular reaction to environmental stress in the majority of patients.
Trafficking Pathways and Characterization of CD4 and CD8 Cells Recruited to the Skin of Humans Experimentally Infected withHaemophilus ducreyi
Authors: Humphreys Tricia L. , Baldridge Lee Ann , Billings Steven D. , Campbell James J. , Spinola Stanley M.
Published: June 2005

T-cell homing to infected skin is not well studied in humans. We examined sites experimentally infected withHaemophilus ducreyiby immunohistochemistry and flow cytometry for expression of receptors and ligands involved in cutaneous T-cell homing and determined the phenotypes of the T cells that trafficked to skin. Endothelial cells expressed E-selectin in infected but not uninfected skin, while peripheral node addressin (PNAd) was minimally expressed in all samples. CC chemokine ligand 27 (CCL27) was expressed in the epidermis and endothelium of both infected and uninfected skin. Interestingly, CCL21, a chemokine thought to be associated principally with T-cell trafficking in the lymphatic compartment, was highly expressed on the endothelium of infected skin. Few naive cells were present in experimental lesions, emphasizing the combined role of PNAd and CCL21 in trafficking of this subset. Memory cells (CD45RA−) dominated both CD4 and CD8 T-cell populations at the site of infection. Effector memory (CD45RA−CD27−) CD4+and CD8+T cells were enriched in lesions. Although the CC chemokine receptor 7-positive (CCR7+) population of both central memory (CD45RA−CD27+) and effector memory cells was not enriched in the skin compared to peripheral blood, CCR7+cells were not precluded from entering infected skin. Taken together with our previous work (D. Soler, T. L. Humphreys, S. M. Spinola, and J. J. Campbell, Blood 101:1677-1683, 2003), these studies led us to propose a model of memory T-cell trafficking to skin in response to experimentalH. ducreyiinfection.
Antagonizing Deactivating Cytokines To Enhance Host Defense and Chemotherapy in Experimental Visceral Leishmaniasis
Authors: Murray Henry W. , Flanders Kathleen C. , Donaldson Debra D. , Sypek Joseph P. , Gotwals Philip J. , Liu Jianguo , Ma Xiaojing
Published: June 2005

In experimental visceral leishmaniasis, inhibition of interleukin 10 (IL-10) signaling enhances Th1-cell-associated responses, promoting gamma interferon (IFN-γ) secretion, granuloma assembly, macrophage activation with substantial liver parasite killing, and synergy with pentavalent antimony (Sb) chemotherapy. To determine if inhibiting other suppressive cytokines has similar therapeutic potential,Leishmania donovani-infected BALB/c mice were injected with anti-IL-4 monoclonal antibody or receptor fusion antagonists of IL-13 or transforming growth factor β (TGF-β). Targeting IL-13 or TGF-β enabled inhibition ofL. donovanireplication but little parasite killing; anti-IL-4 had no effect. None of the three antagonists promoted IFN-γ production, granuloma maturation, or Sb efficacy. Excess IL-13 and TGF-β exacerbated liver infection; however, effects were transient. Among IL-10, IL-4, IL-13, and TGF-β, cytokines capable of disabling Th1-cell mechanisms (including those which support chemotherapy), IL-10 appears to be the appropriate target for therapeutic inhibition in visceralL. donovaniinfection.
Local Peroxynitrite Formation Contributes to Early Control of
Cryptosporidium parvum
Infection
Authors: Gookin Jody L. , Allen Jessica , Chiang Sophia , Duckett Laurel , Armstrong Martha U.
Published: June 2005

In intestinal inflammation, mucosal injury is often exacerbated by the reaction of NO with neutrophil-derived superoxide to form the potent oxidant peroxynitrite. Peroxynitrite also has antimicrobial properties that aid in the killing mechanism of macrophages and neutrophils.
Cryptosporidium parvum
parasitizes intestinal epithelium, resulting in loss of epithelial cells and mucosal inflammation. Synthesis of NO is significantly increased and arises from the induced expression of inducible nitric oxide synthase (iNOS) by the infected epithelium. Inhibition of iNOS results in intensified epithelial parasitism and oocyst excretion. We hypothesized that formation of peroxynitrite is restricted to sites of iNOS expression by the epithelium and contributes to host defense in
C. parvum
infection. Accordingly, the location and biological effects of peroxynitrite formation were examined in neonatal piglets infected with
C. parvum
. Infected piglets were treated daily with a selective iNOS inhibitor [
L
-N6-(1-iminoethyl)-lysine] or one of two peroxynitrite scavengers [5,10,15,20-tetrakis(
N
-methyl-4′-pyridyl)porphyrinato iron(III) or uric acid] or received vehicle. At peak infection, peroxynitrite formation was restricted to sites of iNOS expression by parasitized epithelium and lamina propria of the apical villi. Peroxynitrite formation was dependent on iNOS activity and was inhibited by treatment with peroxynitrite scavengers. Scavengers increased the number of intracellular parasites and the number of infected epithelial cells present per villus and significantly exacerbated oocyst excretion. Recovery from infection was not delayed by ongoing treatment with scavenger. The present results are the first to demonstrate an in vivo role for peroxynitrite formation in acute mucosal defense against a noninvasive intestinal epithelial pathogen.
Short Fimbriae of
Porphyromonas gingivalis
and Their Role in Coadhesion with
Streptococcus gordonii
Authors: Park Yoonsuk , Simionato M. Regina , Sekiya Kachiko , Murakami Yukitaka , James Deanna , Chen Weibin , Hackett Murray , Yoshimura Fuminobu , Demuth Donald R. , Lamont Richard J.
Published: June 2005

Porphyromonas gingivalis
, one of the causative agents of adult periodontitis, attaches and forms biofilms on substrata of
Streptococcus gordonii
. Coadhesion and biofilm development between these organisms requires the interaction of the short fimbriae of
P. gingivalis
with the SspB streptococcal surface polypeptide. In this study we investigated the structure and binding activities of the short fimbriae of
P. gingivalis
. Electron microscopy showed that isolated short fimbriae have an average length of 103 nm and exhibit a helical structure with a pitch of ca. 27 nm. Mfa1, the major protein subunit of the short fimbriae, bound to SspB protein, and this reaction was inhibited by purified recombinant Mfa1 and monospecifc anti-Mfa1 serum in a dose-dependent manner. Complementation of a polar Mfa1 mutant with the
mfa1
gene restored the coadhesion phenotype of
P. gingivalis
. Hence, the Mfa1 structural fimbrial subunit does not require accessory proteins for binding to SspB. Furthermore, the interaction of Mfa1 with SspB is necessary for optimal coadhesion between
P. gingivalis
and
S. gordonii
.
Role of Mitogen-Activated Protein Kinases and NF-κB in the Regulation of Proinflammatory and Anti-Inflammatory Cytokines byPorphyromonas gingivalisHemagglutinin B
Authors: Zhang Ping , Martin Michael , Michalek Suzanne M. , Katz Jannet
Published: June 2005

Hemagglutinin B (HagB) is a nonfimbrial adhesin expressed on the surface ofPorphyromonas gingivalisand has been implicated as a potential virulence factor involved in mediating the attachment of the bacteria to host cells. However, the molecular mechanisms underlying host responses to HagB and their roles in pathogenesis have yet to be elucidated. Mitogen-activated protein kinases (MAPKs) are activated following engagement of a variety of cell surface receptors via dual tyrosine and threonine phosphorylation and are thought to be involved in various cellular responses. The purpose of this study was to determine the role of intracellular signaling pathways including the MAPKs and NF-κB in regulating the production of proinflammatory and anti-inflammatory cytokines following stimulation of murine macrophages with recombinant HagB (rHagB). Stimulation of peritoneal macrophages with rHagB resulted in the production of the proinflammatory cytokines interleukin-12p40 (IL-12p40), gamma interferon (IFN-γ), and tumor necrosis factor alpha, as well as the anti-inflammatory cytokine IL-10. We also demonstrated the activation of extracellular signal-related kinase (ERK), c-Jun NH2-terminal protein kinase (JNK), and p38 MAPKs by rHagB-stimulated macrophages. Furthermore, blocking of the ERK and p38 signaling pathways by using specific inhibitors revealed differential regulatory roles in the rHagB-mediated production of proinflammatory and anti-inflammatory cytokines. ERK and p38 were important in down-regulation of IL-12p40 and IFN-γ production and up-regulation of IL-10 production. The enhanced levels of IL-12p40 in rHagB-stimulated macrophages by inhibition of ERK or p38 activity were partially attributable to the inhibition of IL-10 production. Moreover, NF-κB was found to be critical for up-regulation of IL-12p40 and down-regulation of IL-10 production in rHagB-stimulated macrophages. Taken together, our results demonstrate a role for the p38 and ERK pathways and the transcription factor NF-κB in modulating key immunoregulatory cytokines involved in the development of immune responses toP. gingivalisHagB.
Activation of Lipid Metabolism Contributes to Interleukin-8 Production duringChlamydia trachomatisInfection of Cervical Epithelial Cells
Authors: Fukuda Elaine Y. , Lad Sonya P. , Mikolon David P. , Iacobelli-Martinez Milena , Li Erguang
Published: June 2005

Chlamydia trachomatisinfection is the most common cause of bacterial sexually transmitted diseases. Infection of the urogenital tract byC. trachomatiscauses chronic inflammation and related clinical complications. Unlike other invasive bacteria that induce a rapid cytokine/chemokine production, chlamydial infection induces delayed inflammatory response and proinflammatory chemokine production that is dependent on bacterial growth. We present data here to show that the lipid metabolism required for chlamydial growth contributes toChlamydia-induced proinflammatory chemokine production. By gene microarray profiling, validated with biochemical studies, we found thatC. trachomatisLGV2 selectively upregulated PTGS2 (COX2) and PTGER4 (EP4) in cervical epithelial HeLa 229 cells. COX2 is an enzyme that catalyzes the rate-limiting step of arachidonic acid conversion to prostaglandins, including prostaglandin E2 (PGE2) and other eicosanoids, whereas EP4 is a subtype of cell surface receptors for PGE2. We show thatChlamydiainfection induced COX2 protein expression in both epithelial cells and peripheral blood mononuclear cells and promoted PGE2 release. Exogenous PGE2 was able to induce interleukin-8 release in HeLa 229 epithelial cells. Finally, we demonstrated that interleukin-8 induction byChlamydiainfection or PGE2 treatment was dependent on extracellular signal-regulated kinase/mitogen-activated protein activity. Together, these data demonstrate that the host lipid remodeling process required for chlamydial growth contributes to proinflammatory chemokine production. This study also highlights the importance of maintaining a balanced habitat for parasitic pathogens as obligate intracellular organisms.
Regulatory T Cells Modulate Th2 Responses Induced byBrugia pahangiThird-Stage Larvae
Authors: Gillan Victoria , Devaney Eileen
Published: June 2005

Infection of BALB/c mice withBrugia pahangithird-stage larvae (L3) results in the production of interleukin-4 (IL-4), IL-5, and IL-10 with a resultant down-regulation in Th1 responses. Previously, this was thought to reflect a skewing of immune responses towards a Th2 phenotype by the infective stage of the parasite. In this study, we show that exposure to the L3 ofBrugiaalso induces the expansion of a population of CD4 cells that express CD25 and cytotoxic-T-lymphocyte-associated antigen 4 in an IL-4-independent fashion. By quantitative reverse transcription-PCR, we show that the CD25+population is highly enriched in mRNA for theFoxp3transcription factor and that these cells express significantly moreIL-10mRNA than the CD25−population, suggesting a likely regulatory phenotype. The functional capacity of these cells was demonstrated using a neutralizing CD25 monoclonal antibody (MAb). Mice treated with this MAb demonstrated elevated levels of antigen (Ag)-specific proliferation in vitro, and levels of Ag-specific Th2 cytokines were significantly increased. These results suggest a complex network of regulation in L3-infected mice with Th2 cells limiting the Th1 response, while T-regulatory cells modulate Th2 responses.
Characterization of a Human Monoclonal Antibody against Shiga Toxin 2 Expressed in Chinese Hamster Ovary Cells
Authors: Akiyoshi D. E. , Rich C. M. , O'Sullivan-Murphy S. , Richard L. , Dilo J. , Donohue-Rolfe A. , Sheoran A. S. , Chapman-Bonofiglio S. , Tzipori S.
Published: June 2005

Shiga toxin-producingEscherichia coliinfections can often lead to the development of hemolytic-uremic syndrome (HUS) in a small percentage of infected humans. Patients with HUS receive only supportive treatment as the benefit of antibiotic therapy remains uncertain. We have previously reported the generation and preclinical evaluation of neutralizing human monoclonal antibodies (HuMAbs) against the Shiga toxins (Stx). In this paper, we describe the expression in Chinese hamster ovary (CHO) cells of 5C12 HuMAb, which is directed against the A subunit of Stx2. The cDNAs of the light and heavy chain immunoglobulin (Ig) variable regions of 5C12 HuMAb were isolated and cloned into an expression vector containing human IgG1 constant regions. The vector was transfected into CHO cells, and transfectants secreting Stx2-specific antibody were screened by an Stx2-specific enzyme-linked immunosorbent assay. The CHO-produced recombinant 5C12 (r5C12) showed similar specificity and binding affinity to Stx2 as the parent hybridoma-produced 5C12. More significantly, the r5C12 displayed the same neutralizing activity as the parent 5C12 in vitro and in vivo. In the mouse toxicity model, both antibodies significantly and equally prolonged survival at a dose of 0.312 μg/mouse. The data showed that since r5C12, produced in CHO cells, was equally effective as the parent 5C12, it is our choice candidate as a potential prophylactic or therapeutic agent against hemolytic-uremic syndrome.
Thymidine-Dependent
Staphylococcus aureus
Small-Colony Variants Are Associated with Extensive Alterations in Regulator and Virulence Gene Expression Profiles
Authors: Kahl Barbara C. , Belling Gunnar , Becker Petra , Chatterjee Indranil , Wardecki Katrin , Hilgert Karin , Cheung Ambrose L. , Peters Georg , Herrmann Mathias
Published: June 2005

Chronic airway infection is a hallmark of cystic fibrosis (CF) and many CF patients are infected persistently by
Staphylococcus aureus
. Thymidine-dependent trimethoprim-sulfamethoxazole (SXT)-resistant
S. aureus
small-colony variants (SCVs), often in combination with isogenic normal
S. aureus
phenotypes, are highly prevalent and persistent in airway secretions of CF patients due to long-term SXT therapy (B. Kahl, M. Herrmann, A. S. Everding, H. G. Koch, K. Becker, E. Harms, R. A. Proctor, and G. Peters, J. Infect. Dis.
177:
1023-1029, 1998). In this report, SCVs were compared to normal
S. aureus
by transcription analysis of important regulator (
sigB
,
sarA
, and
agr
) and virulence (α-hemolysin,
hla
, and protein A,
spa
) genes. Growth curve analyses revealed longer doubling times and lower final densities for SCVs than for normal strains.
sigB
activity was measured by transcription analysis of the
sigB
target gene
asp23
. For nearly all SCVs, expression of all regulators was decreased as assessed by
asp23
reverse transcription-PCR for
sigB
and Northern analysis for
sarA
and
agr
. These results are in agreement with diminished
hla
signals in all SCVs and increased
spa
signals in 5 of 10 SCVs compared to the isogenic normal
S. aureus
. Both supplementation of SCVs with thymidine and activation of the
agr
quorum-sensing system by the supernatant of the isogenic normal strain reversed transcription to almost normal levels. In conclusion, multiple changes in growth characteristics and in regulator and virulence gene expression render SCVs less virulent and allow them to survive in the hostile environment present in the airways of CF patients, thereby illustrating adaptation of the bacteria during long-term persistence.