bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Paroxysmal Hemicrania and Hemicrania Continua. Parenteral Indomethacin: The ‘Indotest’
Authors: Antonaci Fabio , Pareja Juan A. , Caminero Ana B. , Sjaastad Ottar
Published: June 2003

The interval between indomethacin administration and clinical response may be clinically relevant in the assessment of chronic paroxysmal hemicrania and hemicrania continua and other unilateral headache disorders with which they can be confounded. Eight patients with chronic paroxysmal hemicrania (6 women and 2 men) and 12 patients with hemicrania continua (8 women and 4 men) were entered into the study. The patients were given 50 mg of indomethacin intramuscularly (IM) on day 1 and some of them 100 mg IM on day 2 in an open fashion. The usual attack pattern was reestablished prior to the second test.

The mean interval between attacks before the two injections (51 ± 18 minutes) in chronic paroxysmal hemicrania was significantly shorter than the mean after each of the two indomethacin injections (50 mg = 493 ± 251 minutes; 100 mg = 668 ± 211 minutes; P0.001; Mann‐Whitney test).

In every patient, there was a clear refractory period after indomethacin. Since the first “expected” attack after indomethacin administration did not occur, it can, with reasonable certainty, be assumed that the protective phase was initiated already prior to the time of the next “anticipated” attack. The mean attack duration was 22 minutes (last three attacks prior to test). The mean interval between the onset of two consecutive pretest attacks was 73 minutes. Since the interval between attacks was rather stable, one is, therefore, probably allowed to assume that the absolute protective effect of indomethacin on average had begun somewhere between 22 (mean attack duration) and 73 minutes after indomethacin injection.

Similarly, in hemicrania continua, the time between 50‐mg indomethacin injection and complete pain relief was 73 ± 66 minutes. The pain‐free period after indomethacin injection was around 13 hours (ie, 13 ± 8 hours after 50 mg and 13 ± 10 hours after 100 mg).

The use of a test dosage of 50 mg of indomethacin IM (‘indotest’) gives a clear‐cut answer and may be a useful tool in the diagnostic arsenal in every unilateral headache for a proper clinical assessment. A diagnosis of chronic paroxysmal hemicrania or hemicrania continua is a serious matter because it may imply life‐long treatment with a potentially noxious drug. It is, therefore, of the utmost importance that an ‘indotest’ is carried out in a standard fashion. In the future, the rules set forth in the present context should be followed, at least in scientific studies.

Pain pressure thresholds at cranial and extracranial levels were not significantly modified after indomethacin injection in any of the headaches.
The Transient Syndrome of Headache With Neurologic Deficits and CSF Lymphocytosis. Report of a Case Without Severe Headache
Authors: Oldani Alessandro , Marcone Alessandra , Zamboni Michele , Zucconi Marco , Ferini‐Strambi Luigi
Published: June 2003

It has been recently reported that the occurrence of severe headache associated with temporary neurologic deficits and CSF lymphocytic pleocytosis is highly suggestive of the so‐called “transient syndrome of headache with neurologic deficits and CSF lymphocytosis.” In particular, in almost all of the 40 patients reported in the literature to date, the head pain was severe and of a type not previously experienced by the patient. In the present case report, we describe a patient who fulfilled almost all the proposed diagnostic criteria, except for the lack of a severe headache. Probably, a severe headache is not a compulsory feature of this syndrome. Some patients have rather mild headache accompanying their episodes of neurologic symptoms, and some attacks occur without any accompanying headache. It is possible that in some cases the absence of a severe headache, and thus the lack of CSF analysis, lead to misdiagnosis. Therefore, the prevalence of this syndrome could be underestimated.
Masturbatory‐Orgasmic Extracephalic Pain
Authors: Jacome Daniel E.
Published: June 2003

Two single men, one with compressive spondylitic cervical myelopathy and another with tethered cord and intraspinal lipoma, experienced severe paroxysmal ice picklike pains, solely referred to the neck in the first and to the groin and genitalia in the second, that were precipitated by masturbation and masturbatory orgasms. Continuous, but less intense, background pain was reported by both patients over the same anatomic areas. Neither had intracranial lesions, epilepsy, or suffered from migraine. Recently, extratrigeminal ice pick status was reported in this journal. These two unusual cases represent examples of extracephalic ice picklike pain triggered by sexual activity, in the absence of orgasmic cephalgia.
Dosing of Oral Sumatriptan: A Review of Our First 104 Patients
Authors: Solomon Glen D. , Frizelis Karen , Becker Judith , Kunkel Robert S.
Published: June 2003

Background.—The introduction of oral sumatriptan in the United States at doses of 25 and 50 mg, compared with 100‐mg tablets worldwide, has created the need to develop a protocol for appropriate dosing.

Methods.—We evaluated the first 104 patients in our practice to treat two migraine attacks with oral sumatriptan. For their first treatment with oral sumatriptan, patients were evaluated on their response to 25‐mg tablets and the total number of tablets taken. For their second treatment, patients were evaluated on their response to sumatriptan, number of 25‐mg tablets taken, and dosage prescribed for future migraines.

Results.—

Response to Treatment and Number of 25‐mg Tablets Taken

Response to Treatment, No. (%) of Patients
No. of 25‐mg Tablets, No. (%) of Patients

Good
Fair
Poor
1
2
3
4

First headache
51 (55)
19 (21)
22 (24)
35 (34)
64 (62)
4 (4)
1 (1)

Second headache
70 (78)
12 (13)
8 (9)
28 (28)
51 (51)
3 (3)
18 (18)

After the second treatment, 41 patients (40%) continued therapy with 25‐mg tablets, 54 (53%) were prescribed 50‐mg tablets, 2 patients (2%) were prescribed two 50‐mg tablets, and 5 patients (5%) were prescribed injectable sumatriptan. Seventy patients had previously used injectable sumatriptan, while 34 had not previously used sumatriptan. There were no significant differences in their response to oral sumatriptan.

Conclusion.—Oral sumatriptan was effective in clinical practice at doses of 25 and 50 mg. The majority of patients required more than one 25‐mg tablet for a migraine attack, reflecting both inadequacy of dosing for some migraines and recurrence of headache, yet 40% of patients continued on treatment with 25‐mg tablets. There were no significant differences in response to therapy in patients being switched from injectable to oral sumatriptan compared with those initiating therapy with oral sumatriptan. Both tablet strengths of oral sumatriptan are useful in clinical practice.
Epidemiologic and Clinical Characteristics of Migraine and Tension‐Type Headache in Korea
Authors: Roh J. K. , Kim J. S. , Ahn Y. O.
Published: June 2003

This is the first population‐based epidemiologic study of chronic headache in South Korea. The diagnosis and classification of headache was according to the criteria of the International Headache Society. Sixty‐eight percent of the studied population experienced headache during the preceding year. The estimated prevalences were 22.3% for migraine (male 20.2%, female 24.3%) and 16.2% for tension‐type headache (male 17.8%, female 14.7%). In migraine, the 15‐to 19‐year age group showed maximal prevalence in both sexes (male 28.5%, female 34.7%). The prevalence of tension‐type headache was highest in the 50‐ to 59‐year age group in men(24.2%) and in the 20‐ to 29‐year age group in women(20.2%). In migraine, headache intensity was more severe in women than in men, but in tension‐type headache there was no difference in the severity of headache between the sexes. Phonophobia was the most common associated symptom of migraine (65.1%). In the migraine with aura group, the most common aura was visual disturbance, including scintillation and image distortion (82.3%). Only 24.4% of migraineurs and 12.3% of patients with tension‐type headache had ever consulted a doctor for headache. The prevalence of migraine was not lower than in western countries and much higher than in previous studies conducted in other Asian countries.
Headache and Facial Pain Responsive to Botulinum Toxin: An Unusual Presentation of Blepharospasm
Authors: Johnstone Sharon J. , Adler Charles H.
Published: June 2003

The diagnosis of blepharospasm is rarely considered in patients complaining of face pain or headache. This patient illustrates the importance of looking for blepharospasm in patients who present with headache or face pain, as her pain and blepharospasm were successfully treated with botulinum toxin type A injections.
Assessing the Severity of Migraine: Development of the MIGSEV Scale
Authors: El Hasnaoui Abdelkader , Vray Muriel , Richard Alain , Nachit‐Ouinekh Fatima , Boureau François , For The MIGSEV Group
Published: June 2003

Objectives.—To identify items that serve to assess the severity of migraine with a high level of clinical and psychometric relevance and to combine these into a unitary severity scale.

Background.—Severity of migraine is an important determinant of patient quality of life and of health care resource utilization. Despite this, no validated method exists for measuring migraine severity.

Methods.—After selection from the medical literature items of potential relevance to the severity of migraine, consensus meetings led to a choice of items which subsequently were refined further on the basis of patient interviews. The psychometric properties of those items then were assessed in a survey involving 287 migraineurs. The methods used to test reliability and validity included test‐retest, calculation of Cronbach α coefficient, analysis of factorial structure using principal components analysis, a comparison of the agreement between doctors' and patients' assessments, and correlation with a validated quality‐of‐life questionnaire. The most pertinent items revealed by the factorial analysis were combined in a unitary scale.

Results.—Seven items reflecting severity were identified by expert consensus. These were intensity of pain, tolerability, disability in daily activities, presence of nausea or vomiting, resistance to treatment, duration of attacks, and frequency of attacks. Principal components analysis identified 3 dimensions accounting for 65% of the overall variance related to intensity of attacks, resistance to treatment, and frequency of attacks. The internal consistency and the reproducibility of the items appeared quite satisfactory, and variations in these items were correlated with quality‐of‐life scores. The 4 items related to intensity of attacks were combined into a single scale with 3 response modalities.

Conclusions.—The 3 dimensions identified by this investigation appeared medically relevant and to have good psychometric properties. The items on the intensity dimension can be used to generate a simple scale for assessing migraine attack severity.
Factors Associated With Burden of Primary Headache in a Specialty Clinic
Authors: Cassidy Eugene M. , Tomkins Esther , Hardiman Orla , O'Keane Veronica
Published: June 2003

Objective.—To examine factors associated with social, occupational, and psychological burden of common primary headache (migraine and tension‐type headache).

Background.—The personal and social burden of primary headache is high. Health, occupational, social, and psychological factors contributing to burden in people with disabling headache have not been fully unravelled.

Methods.—One hundred eighty consecutive patients with either migraine or tension‐type headache attending a specialty headache outpatient clinic for the first time were evaluated over a 9‐month period. Headache subtype was operationally defined according to International Headache Society criteria. Headache frequency, duration, and severity were recorded. Occupational and social disability were quantified using the Migraine Disability Assessment questionnaire. Psychological burden was quantified using the 28‐item General Health Questionnaire, the Beck Depression Inventory, and the State‐Trait Anxiety Inventory. Premorbid vulnerability to life stress was quantified using the neuroticism subscale of the Eysenck Personality Inventory.

Results.—Patients with frequent (chronic) headache scored higher on the Migraine Disability Assessment questionnaire and had higher Beck Depression Inventory and General Health Questionnaire depression scores than those with less frequent (episodic) headache. Frequency of headache, but not pain severity, duration, or diagnosis, predicted both Migraine Disability Assessment total disability and General Health Questionnaire/Beck Depression Inventory depression. Neuroticism was predictive of depression but not disability. Patients with chronic migraine had the highest depression and disability scores.

Conclusion.—The number of days per month with headache is a key determinant of headache‐related burden in those attending specialty clinics. Frequent (chronic) headache is associated with significantly higher psychopathology scores and general social impairment, but the direction of this relationship is not clear. Those with migraine and chronicity are the most impaired.
Differences in Anger Expression Between Individuals With and Without Headache After Controlling for Depression and Anxiety
Authors: Nicholson Robert A. , Gramling Sandra E. , Ong Jason C. , Buenevar Luis
Published: June 2003

Objective.—To evaluate whether anger and anger expression are different between persons with and without headache after controlling for depression and anxiety.

Background.—Persons with headache may experience more problems with anger and its expression when compared with persons without headache. It is important to establish whether differences exist for persons with and without headache on trait anger and anger expression independent of depression and anxiety. To date, however, this issue has received little attention in the empirical literature. The current study measured trait anger, anger‐in, hostility, anxiety, and depression among persons with and without headache, and evaluated whether trait anger and anger‐in differentiated groups independent of depression and anxiety.

Methods.—Participants were 422 adults recruited from a larger study within a university setting. Of those, 171 suffered from headache (mean age, 21 years; 81% were female; 69% were white; mean years with pain, 7.53). Another 251 sex‐matched individuals (mean age, 21 years; 81% female; 62% white) met criteria for the headache‐free group. Participants provided information regarding their headache characteristics and were administered affective trait measures (Trait version of the State‐Trait Anxiety Inventory, Brief Symptom Inventory‐Depression), trait anger measures (Trait Anger Scale, Cook‐Medley Hostility Scale), and a measure of the extent to which individuals hold their anger in.

Results.—Multivariate analysis of variance revealed significant differences between the 2 groups (Wilks λ  =  .86, P  <  .001, η2  =  .14). Step‐down analysis revealed that even after controlling for all other variables, those in the headache group had higher levels of anger‐in (P  <  .001, η2  =  .08; mean, 18.98 versus 15.68). Trait anger and hostility did not differ between groups after controlling for depression and anxiety. Logistic regression revealed that anger‐in contributed most to predicting headache status (P  <  .001; partial r  =  .23).

Conclusions.—The current findings indicate that persons with headache hold their anger in more than those without headache even after controlling for levels of trait anger, depression, and anxiety. However, after controlling for depression and anxiety, individuals no longer differed on trait anger. Also, anger‐in was the strongest predictor of headache. The current findings suggest that holding anger in is more common among headache sufferers. Given recent findings regarding the negative effect of holding anger in among persons with pain conditions, this may be an important factor to evaluate when considering psychological/emotional factors affecting headache.
Postural Headache and Cerebrospinal Fluid Leak: Believing Is Seeing
Authors: Goadsby Peter , Jager H. Rolf
Published: June 2003

A 33‐year‐old woman developed persistent postural headache following epidural anesthesia (L2‐L3 level). Iohexol myelography (L5‐S1 puncture) demonstrated no epidural extravasation of contrast material (Figure A), but subsequent computed tomography (CT) axial images (B, C) revealed leakage of dye through the needle track of the L5‐S1 puncture (arrows). No leakage of contrast medium was found at the site of the L2‐L3 epidural puncture.
Influence of testosterone on the electrical properties of scrotal nerves at the cutaneous and spinal levels in the male rat
Authors: Manzo Jorge , Garcí Luis I. , Camacho Miguel A. , Hernández María Elena , Pacheco Pablo
Published: June 2003

Abstract The scrotal nerves in the rat were studied electrophysiologically to describe their topographic organization in the skin and in the dorsal roots, and to determine if the electrical properties of these afferents are under the influence of testosterone. There are 2 afferent nerve branches innervating this area, the proximal scrotal branch supplying the proximal half of the scrotum (PSb), and the distal scrotal branch supplying the distal half (DSb). Results showed that afferent axons from PSb enter the spinal cord through the L5 and L6 dorsal roots, and axons from DSb enter the cord through the L6 and S1 dorsal roots. Mechanical stimulation of the scrotal skin exposed 3 dermatome areas, the L5, L6, and S1, with L6 being the longest dermatome with intermingled terminals from PSb and DSb. Decreased levels of testosterone after castration increased the threshold to trigger the activity of scrotal afferents, and the exogenous administration of the hormone reverted it. This effect was similar in the dorsal penile nerve. The decrease in androgen levels produced a reduction in the skin sensory field to mechanical stimuli that was restored after the administration of the hormone. As the scrotal nerves are highly stimulated during copulation in parallel with the dorsal penile nerve, it is suggested that the sensory field of the scrotal skin could be closely related to the modifications in sexual behavior after testosterone manipulation.
Antibodies to myelin‐associated glycoprotein accelerate preferential motor reinnervation
Authors: Mears Simon , Schachner Melitta , Brushart Thomas M
Published: June 2003

Abstract  Predegeneration of nerve enhances its ability to support axon regeneration. Trophic factors are upregulated by reactive Schwann cells while potentially inhibitory molecules are removed. These experiments isolate the effects of one such inhibitory molecule, the myelin‐associated glycoprotein (MAG), to determine its role in modifying regeneration after nerve repair. Suture of the mouse femoral nerve was followed by daily intraperitoneal injection of antibodies to MAG, antibodies to HNK‐1, a specific muscle pathway marker, or no further treatment. Regeneration was assayed by double‐labeling the femoral cutaneous and muscle branches with horseradish peroxidase and fluoro‐gold after 4 weeks or 6 weeks of regeneration. Four weeks after nerve repair, selective reinnervation of the muscle branch by motoneurons, or preferential motor reinnervation (PMR), was not seen in either controls or L2‐antibody‐treated animals. In contrast, treatment with MAG antibodies resulted in dramatic PMR. By 6 weeks, the controls had achieved borderline specificity, substantial PMR developed in the L2 antibody group and the MAG group changed little. Blocking access to MAG in the distal nerve stump thus accelerated and enhanced PMR. Sensory regeneration was depressed by both antibody treatments at 4 weeks but recovered by 6 weeks. Antibody administration has a generalized effect on sensory regeneration that is unrelated to the behavior of motoneurons in the same nerve.
Microvasculitic paraproteinaemic polyneuropathy and B‐cell lymphoma
Authors: Turner Martin R. , Warren Jason D. , Jacobs Jean M. , Groves Mike J. , Yong Kwee , Honan William P. , Thomas P. K. , Reilly And Mary M.
Published: June 2003

Abstract  Microvasculitis may play a greater part in the pathogenesis of paraproteinaemic neuropathies than is generally recognised, producing tissue destruction by convergent immune and physical mechanisms. We present a patient with a clinical syndrome of mononeuritis multiplex and a circulating IgM lambda paraprotein, in whom bone marrow aspiration revealed a lymphoplasmacytoid lymphoma. Microvasculitic changes were present in the first nerve biopsy, and the second showed extensive destruction of neural architecture and deposition of IgM‐related material. A 2‐stage pathogenic cascade is postulated and explored with a review of the relevant literature.
Sodium Valproate in the Management of Painful Neuropathy in Type 2 Diabetes – a Randomized Placebo Controlled Study
Authors: Kochar DK , Jain N , Agarwal RP , Srivastava T , Agarwal P , Gupta S
Published: June 2003

OBJECTIVE: To study the effectiveness and safety aspects of sodium valproate in the management of painful neuropathy in patients of type 2 diabetes mellitus. MATERIAL AND METHODS: A randomized double‐blind placebo controlled trial of sodium valproate was done in type 2 diabetic patients to assess its efficacy and safety in the management of painful neuropathy. We screened 60 patients but eight patients could not complete the study; hence, the present study was done on 52 patients. Each patient was assessed by clinical examination, pain score by short form of the McGill pain questionnaire (SF‐MPQ) and electrophysiological examination, which included motor and sensory nerve conduction velocity, amplitude and H‐reflex initially and at the end of 1 month of treatment. RESULTS: Significant improvement was noticed in the pain score of patients receiving sodium valproate in comparison to patients receiving placebo at the end of 1 month (P < 0.05). The changes in electrophysiological data were not significant. The drug was well tolerated by all patients except one who developed a raised aspartate transaminase (AST)/alanine transaminase (ALT) level after 15 days of treatment. CONCLUSION: Sodium valproate is a well‐tolerated drug and provides significant subjective improvement in painful diabetic neuropathy. These data provide a basis for future trials of longer duration in a larger group of patients.
Chronic Inflammatory Demyelinating Neuropathy and Axonal Cytoskeleton: Morphometric and Immunocytochemical Data
Authors: Fressinaud C , Jean I
Published: June 2003

We report morphometric and immunocytochemical data obtained from nervous biopsy in 7 patients with chronic inflammatory demyelinating neuropathy (CIDP), compared to 5 controls (without neurological involvement). Fiber loss was present in all cases and reached 50 p. 100 or more in 4 cases. The g myelination ratio was elevated in 3 cases only, indicating demyelination. The number of fibers labelled for the L subunit of neurofilaments was normal in cases with moderate fiber loss and dropped down for densities <3900/mm2(4 cases). Labelling with anti‐GAP43 antibody was considerably increased in 3 cases, but did not correlate with fiber density or disease duration. These data confirm the importance of axonal lesions in CIDP and offer the opportunity to discuss their pathophysiological mechanisms.
Altered Arachidonic Acid Biosynthesis and Antioxidant Protection Mechanisms in Schwann Cells Grown in Elevated Glucose
Authors: Miinea C , Kuruvilla R , Merrikh H , Eichberg J.
Published: June 2003

In cultured Schwann cells, elevated glucose induces alterations in arachidonic acid metabolism that cause a decrease in the content of glycerophospholipid arachidonoyl‐containing molecular species (ACMS). This could result from decreased de novo arachidonic acid biosynthesis, or increased arachidonic acid release from phospholipids. Incorporation of radioactive 8,11,14‐eicosatrienoic acid into ACMS was lower for cells grown in 30 mm versus 5 mm glucose, consistent with a decrease in Delta5 desaturase activity. However, neither basal arachidonic acid release from prelabeled cells nor stimulated generation of arachidonic acid in the presence of the reacylation inhibitor, thimerosal, the phosphotyrosine phosphatase inhibitor, bipyridyl peroxovanadium, or both together, were altered by varying the glucose concentrations, indicating that arachidonic acid turnover did not contribute to ACMS depletion. Free cytosolic NAD(+)/NADH decreased, whereas NADP(+)/NADPH remained unchanged for cells grown in elevated glucose, implying that decreased desaturase activity is a result of metabolic changes other than cofactor availability. Schwann cells in elevated glucose were susceptible to oxidative stress, as shown by increased malondialdehyde, depleted glutathione levels, and reduced cytosolic superoxide dismutase activity. Glutathione‐altering compounds had no effect on ACMS levels, in contrast to N‐acetylcysteine and alpha‐lipoic acid, which partly corrected ACMS depletion in phosphatidylcholine. These findings suggest that in the Schwann cell cultures, a high glucose level elicits oxidative stress and weakens antioxidant protection mechanisms which could decrease arachidonic acid biosynthesis and that this deficit can be partly corrected by treatment with exogenous antioxidants.
Effect of Treatment of Diabetic Rats with Dehydroepiandrosterone on Vascular and Neural Function
Authors: Yorek MA , Coppey LJ , Gellett JS , Davidson EP , Bing XY , Lund DD , Dillon JS
Published: June 2003

Nutritional supplementation with dehydroepiandrosterone (DHEA) may be a candidate for treating diabetes‐induced vascular and neural dysfunction. DHEA is a naturally occurring adrenal androgen that has antioxidant properties and is reportedly reduced in diabetes. Using a prevention protocol, we found that dietary supplementation of streptozotocin‐induced diabetic rats with 0.1, 0.25, or 0.5% DHEA caused a concentration‐dependent prevention in the development of motor nerve conduction velocity and endoneurial blood flow impairment, which are decreased in diabetes. At 0.25%, DHEA significantly prevented the diabetes‐induced increase in serum thiobarbituric acid‐reactive substances and sciatic nerve conjugated diene levels. This treatment also reduced the production of superoxide by epineurial arterioles of the sciatic nerve. DHEA treatment (0.25%) significantly improved vascular relaxation mediated by acetylcholine in epineurial vessels of diabetic rats. Sciatic nerve Na+−K+−ATPase activity and myoinositol content was also improved by DHEA treatment, whereas sorbitol and fructose content remained elevated. These studies suggest that DHEA, by preventing oxidative stress and perhaps improving sciatic nerve Na+−K+−ATPase activity, may improve vascular and neural dysfunction in diabetes.
Early, Selective, and Marked Loss of Sympathetic Nerves from the Islets of Biobreeder Diabetic Rats
Authors: Mei Q , Mundinger TO , Lernmark A , Taborsky GJ
Published: June 2003

To discover whether islet sympathetic nerves are damaged during the autoimmune destruction of islet B‐cells, we immunostained sections of pancreas from Bio‐Breeder (BB) diabetic rats, using antibodies against vesicular monoamine transporter 2 (VMAT2), a marker of sympathetic nerve terminals. We found a marked decrease in the VMAT2‐positive fiber area in the islets of BB rats that had been diabetic for only 1–2 weeks compared with their nondiabetic controls. In contrast, there was no significant decrease in the VMAT2‐positive fiber area in the exocrine pancreas in these early diabetic BB rats. Furthermore, streptozotocin‐diabetic rats showed no decrease in VMAT2‐positive fiber area in their islets compared with controls. The classical diabetic autonomic neuropathy (DAN) that eventually occurs in the heart was not present in BB diabetic rats at this early stage as evidenced by normal cardiac VMAT2 immunostaining and normal cardiac norepinephrine content. Also, in contrast to DAN, this islet neuropathy did not worsen with duration of diabetes. These data provide evidence of a heretofore unrecognized early sympathetic islet neuropathy (eSIN). Because eSIN occurs selectively in the islet, is rapid in onset, and is associated with autoimmune but not chemically induced diabetes, it is distinct from DAN in location, time course, and mechanism.
Peripheral Nerve Regeneration in Galactosaemic Rats
Authors: King RHM , Muddle JR , Nourallah M , Wong J , Workman JM , Thomas PK
Published: June 2003

The use of galactosaemia as a model for some aspects of diabetic polyneuropathy allows the influence of glycation to be studied independently of other effects. There are well‐studied abnormalities of the peripheral nerves in galactosaemic rats, one of which is that the efficiency of regeneration is initially reduced. One possible cause could be that glycated myelin debris in macrophages is less degradable and interferes with macrophage function. Macrophage recognition and ingestion of myelin glycosylated in vitro increases with the duration of incubation in a sugar‐rich medium. This study was performed to investigate a possible correlation between galactosaemia and regeneration, together with the role of macrophages. Galactosaemia was induced by adding galactose to the rats’ diet for 2 months before injury. Following a crush lesion to the sciatic nerve, regeneration was found to be delayed, demonstrated by a reduction in mean myelinated fibre size and density 1 month after crush, although, 2 and 3 months later, the differences did not reach statistical significance. There were also more macrophages in the galactosaemic rats than in the control animals at all time points. The initial delay in regeneration in galactosaemic rats was therefore only temporary and there was little evidence of long‐term deleterious effects. In addition to the morphometric results, immunohistochemistry showed that there were more macrophages in the galactosaemic rats than in the control animals at all time points. Correlating macrophage and myelinated fibre counts suggests that the persistence of debris‐containing macrophages does not appear to have a significant inhibitory effect on nerve regeneration. No evidence was found for persistent basal laminal tubes around the regenerating clusters.
Trends in Opioid use for Chronic Neuropathic Pain: a Survey of Patients Pursuing Enrollment in Clinical Trials
Authors: Gilron I , Bailey JM
Published: June 2003

PURPOSE: Clinical trials suggest that opioids relieve neuropathic pain and decrease pain‐related disability. We conducted a pilot study of current prescribing trends and patients’ attitudes towards opioids for neuropathic pain. METHODS: A patient questionnaire was completed by individuals pursuing enrollment in neuropathic pain clinical trials at our facility. RESULTS: Of 154 patients with diabetic neuropathy (55.2%), postherpetic neuralgia (29.9%), idiopathic peripheral neuropathy (9.7%) and other neuropathies (5.2%), 73.4% complained of inadequate pain control, the mean pain duration was 4.7 (SD = 4.4) yr and the mean pain intensity (0–10) was 7.7 (SD = 2.3). In this group, 40.9% had never tried opioids and 24.7% had never tried any opioids, tricyclic antidepressants or anticonvulsants. Only 9.7% were receiving long‐acting opioids or “around the clock” dosing whereas 25.3% were receiving opioids on an “as needed” basis. Opioids combined with tricyclic antidepressants and/or anticonvulsants were used in 11.0%. Fear of addiction and adverse effects were expressed by 31.8% and 46.8% respectively. CONCLUSION: These data suggest that barriers to opioid therapy for neuropathic pain include patients’, and possibly physicians’, fears of addiction and adverse effects, which are exaggerated in light of current evidence. The merits of continuous treatment with sustained‐release opioids, “as needed” dosing with short‐acting preparations, or combining opioids with other agents are discussed, Continued research and communication between health professionals, law enforcement officials and legislators is vital in order to facilitate appropriate opioid use which has a minimal negative impact on the public yet optimally benefits individuals who suffer from disabling neuropathic pain.
Peripheral Neuropathy with Hypomyelinating Features in Adult‐onset Krabbe's Disease
Authors: Sabatelli M , Quaranta L , Madia F , Lippi G , Conte A , Lo Monaco M , Di Trapani G , Rafi MA , Wenger DA , Vaccaro AM , Tonali P
Published: June 2003

We describe three brothers suffering from Krabbe's disease with onset in the fifth decade. The proband showed a complete deficiency of leukocyte enzyme galactocerebrosidase and was found to be heterozygous for two previously described mutations: G > A809 and 502T/del consisting of a 30 kb deletion. In all three brothers the neurological examination showed features of asymmetrical peripheral neuropathy associated with pyramidal signs and the electrophysiological examination showed a generalized slowing of nerve conduction velocities. Two patients died at 59 and 61 years of age due to respiratory failure. Both the proband and his brother underwent a sural nerve biopsy. In the former the most striking finding was the presence of uniformly thin myelin sheaths without evidence of demyelination; a complete absence of fibers was found in the latter. Our findings confirm that peripheral neuropathy may be the presenting feature of late‐onset Krabbe's disease. Hypomyelination rather than demyelination may represent the distinguishing pathological finding of this condition.
Chronic Neuropathic Pain is Accompanied by Global Changes in Gene Expression and Shares Pathobiology with Neurodegenerative Diseases
Authors: Wang H , Sun H , Della Penna K , Benz RJ , Xu J , Gerhold DL , Holder DJ , Koblan KS
Published: June 2003

Neuropathic pain is induced by injury or disease of the nervous system. Studies aimed at understanding tile molecular pathophysiology of neuropathic pain have so far focused on a few known molecules and signaling pathways in neurons. However, the pathophysiology of neuropathic pain appears to be very complex and remains poorly understood. A global understanding of the molecular mechanisms involved in neuropathic pain is needed for a better understanding of the pathophysiology and treatment of neuropathic pain. Towards this end, we examined global gene expression changes as well as the pathobiology at the cellular level in a spinal nerve ligation neuropathic pain model using DNA microarray, quantitative real‐time PCR and immunohistochemistry. We found that the behavioral hypersensitivity that is manifested in the persistent pain state is accompanied by previously undescribed changes in gene expression. In the DRG, we found regulation of: (1) immediate early genes; (2) genes such as ion channels and signaling molecules that contribute to the excitability of neurons; and (3) genes that are indicative of secondary events such as neuroinflammation. In addition, we studied gene regulation in both injured and uninjured DRG by quantitative PCR, and observed differential gene regulation in these two populations of DRGs. Furthermore, we demonstrated unexpected co‐regulation of many genes, especially the activation of neuroinflammation markers in both the PINS and CNS. The results of our study provide a new picture of the molecular mechanisms that underlie the complexity of neuropathic pain and suggest that chronic pain shares common pathobiology with progressive neurodegenerative disease.
Dejerine‐Sottas Neuropathy with Multiple Nerve Roots Enlargement and Hypomyelination Associated with a Missense Mutation of the Transmembrane Domain of MPZ/P0
Authors: Simonati A , Fabrizi GM , Taioli F , Polo A , Cerini R , Rizzuto N
Published: June 2003

In a patient affected with a slowly progressive, severe form of Dejerine‐Sottas syndrome, symmetric enlargement of cranial nerves and focal hypertrophy of cervical and caudal roots were detected following MRI. Neuropathological features of the sural nerve disclosed a dramatic loss of myelinated fibres, with skewed‐to‐the‐left, unimodal distribution of the few residual fibres, consistent with the diagnosis of congenital hypomyelination neuropathy. Genetic analysis revealed this condition to be associated with a heterozygous G to A transition at codon 167 in the exon 4 of the MPZ/P0 gene causing a Gly138Arg substitution in the transmembrane domain of the mature MPZ/P0 protein. Focal enlargement of the nerve trunks in demyelinating, hereditary motor and sensory neuropathies (HMSN) was previously reported in both asymptomatic and symptomatic cases with root compression, but peculiar to this case is the diffuse involvement of both cranial and spinal nerves. We believe that the relevance of nerve trunk hypertrophy in HMSN is probably underevaluated: therefore MRI investigation of the head and spine should be included in the diagnostic study of selected HMSN patients. Molecular analysis of peripheral myelin genes will help to rule out misdiagnosed cases.
Phased‐Array Intracardiac Echocardiography for Defining Cavotricuspid Isthmus Anatomy During Radiofrequency Ablation of Typical Atrial Flutter
Authors: Morton Joseph B. , Sanders Prashanthan , Davidson Neil C. , Sparks Paul B. , Vohra Jitendra K. , Kalman Jonathan M.
Published: June 2003

Introduction: Cavotricuspid isthmus (CTI) topography includes ridges, pouches, recesses, and trabeculations. These features may limit the success of radiofrequency ablation (RFA) of typical atrial flutter (AFL). The aim of this study was to assess the utility of phased‐array intracardiac echocardiography (ICE) for imaging the CTI and monitoring RFA of AFL.

Methods and Results: Fifteen patients (mean age

64 ± 9

years) underwent ICE assessment (imaging frequency 7.5–10 MHz) before and after RFA of AFL. The ICE catheter was positioned at the inferior vena cava‐right atrial junction and the following parameters were measured: (1) CTI length from the tricuspid valve to the eustachian ridge; (2) extent of CTI pouching; and (3) thickness pre/post RFA of the anterior, mid, and posterior CTI. CTI length was

35 ± 6 mm

at end‐ventricular systole but shorter

(30 ± 6 mm)

and more pouched at end‐ventricular diastole

(P = 0.02)
. A pouch or recess was seen in 11 of 15 patients (mean depth6 ± 2 mm). The septal CTI was more pouched than the lateral CTI, but the latter had more prominent trabeculations. Trabeculations were seen in 10 of 15 patients, and at these locations the CTI was4.6 ± 1 mmthick. Anterior, mid, and posterior CTI thickness pre‐RFA was4.1 ± 0.8, 3.3 ± 0.5, and2.7 ± 0.9 mm, respectively (P < 0.001by analysis of variance). ICE guided RFA away from unfavorable CTI features (recesses/thick trabeculations). RFA applications created discrete CTI lesions that coalesced, forming diffuse CTI swelling. Post‐RFA thickness was as follows: anterior4.8 ± 0.8 mm (P = NSvs pre); mid3.8 ± 0.8 mm (P = 0.05 vs pre); and posterior3.8 ± 0.8 mm (P = 0.02 vs pre).

Conclusion: Phased‐array ICE permits novel real‐time CTI imaging with excellent endocardial resolution and may facilitate RFA of AFL. (J Cardiovasc Electrophysiol, Vol. 14, pp. 591‐597, June 2003)
Endocardial Mapping of Right Ventricular Outflow Tract Tachycardia Using Noncontact Activation Mapping
Authors: Ribbing Michael , Wasmer Kristina , Mönnig Gerold , Kirchhof Paulus , Loh Peter , Breithardt Günter , Haverkamp Wilhelm , Eckardt Lars
Published: June 2003

Introduction: Activation mapping and pace mapping identify successful ablation sites for catheter ablation of right ventricular outflow tract (RVOT) tachycardia. These methods are limited in patients with nonsustained tachycardia or isolated ventricular ectopic beats. We investigated the feasibility of using noncontact mapping to guide the ablation of RVOT arrhythmias.

Methods and Results: Nine patients with RVOT tachycardia and three patients with ectopic beats were studied using noncontact mapping. A multielectrode array catheter was introduced into the RVOT and tachycardia was analyzed using a virtual geometry. The earliest endocardial activation estimated by virtual electrograms was displayed on an isopotential color map and measured

33 ± 13 msec

before onset of QRS. Virtual unipolar electrograms at this site demonstrated QS morphology. Guided by a locator signal, ablation was performed with a mean of

6.9 ± 2.2

radiofrequency deliveries. Acute success was achieved in all patients. During follow‐up, one patient had a recurrence of RVOT tachycardia. Compared with patients

(n = 21)

who underwent catheter ablation using a conventional approach, a higher success rate was achieved by noncontact mapping. Procedure time was significantly longer in the noncontact mapping group. Fluoroscopy time was not significantly different in the two groups.

Conclusion: Noncontact mapping can be used as a reliable tool to identify the site of earliest endocardial activation and to guide the ablation procedure in patients with RVOT tachycardia and in patients with ectopic beats originating from the RVOT. (J Cardiovasc Electrophysiol, Vol. 14, pp. 602‐608, June 2003)
Role of Autonomic Tone in the Initiation and Termination of Paroxysmal Atrial Fibrillation in Patients Without Structural Heart Disease
Authors: Tomita Takeshi , Takei Manabu , Saikawa Yuko , Hanaoka Takeshi , Uchikawa Shin‐Ichiroh , Tsutsui Hiroshi , Aruga Masakazu , Miyashita Toyohisa , Yazaki Yoshikazu , Imamura Hiroshi , Kinoshita Osamu , Owa Mafumi , Kubo Keishi
Published: June 2003

Introduction: Previous studies have suggested that paroxysmal atrial fibrillation (PAF) of vagal origin often occurs at night and PAF of sympathetic origin occurs during the daytime; however, autonomic tone after spontaneous termination of PAF has not been determined. The aim of this study was to evaluate by heart rate variability (HRV) analysis the relationship between the time of PAF onset and autonomic tone before and after PAF.

Methods and Results: Twenty‐three patients (

65 ± 2

years) who underwent 24‐hour ambulatory monitoring, had one or more episodes of PAF (>30 min), and had maintained normal sinus rhythm for >60 min before/after PAF were enrolled in this study. Mean duration of PAF was

6.2 ± 1.2

hours. HRV parameters were analyzed in a 10‐minutes section at 60 minutes, 20 minutes, and immediately before the onset of PAF and after its termination. PAF began at night in 14 patients (group N) and during the daytime in 9 patients (group D). In group N, the high‐frequency (HF) component and low‐frequency (LF) component showed a significant decrease after PAF; PAF was preceded by a gradual increase in HF and LF. Changes in the LF/HF ratio, however, did not occur before or after PAF. Conversely, group D showed a significant increase in the LF/HF ratio before PAF and a decrease in LF and the LF/HF ratio after PAF, but no changes in HF. These changes in HRV parameters were not influenced by the duration or termination time of PAF.

Conclusion: This study suggests that the autonomic nervous system plays an important role in both the initiation and termination of PAF. Furthermore, the time of PAF onset influences the autonomic tone at the initiation and termination of PAF. (J Cardiovasc Electrophysiol, Vol. 14, pp. 559‐564, June 2003)
Block of HERG‐Carried K+ Currents by the New Repolarization Delaying Agent H 345/52
Authors: Amos Gregory J. , Jacobson Ingemar , Duker Göran , Carlsson Leif
Published: June 2003

Introduction: The aim of this study was to analyze the block of HERG‐carried membrane currents caused by H 345/52, a new antiarrhythmic compound with low proarrhythmic activity, in transfected mouse fibroblasts.

Methods and Results: Using the whole‐cell configuration of the voltage patch clamp technique, it was demonstrated that H 345/52 concentration‐dependently blocked HERG‐carried currents with an IC50 of 230 nM. H 345/52 preferentially bound to the open channel with unusually rapid kinetics and was trapped by channel closure. Voltage‐independent behavior of H 345/52 was observed during both square‐pulse and action potential clamp protocols. In contrast, the Class III agents dofetilide (10 nM) and almokalant (250 nM) demonstrated significant membrane potential‐dependent effects during square‐pulse clamp protocols. When using action potential clamp protocols, voltage dependence was seen with dofetilide but not with almokalant. Mathematical simulations of human ventricular action potentials predicted that the different voltage‐dependent behaviors would not produce marked variations in action potential duration prolongation patterns.

Conclusion: We propose that block of IKr is the principal mechanism by which H 345/52 delays repolarization in human myocardium. The voltage independence of HERG/IKr block is unlikely to underlie the low proarrhythmic potential, and ancillary effects on other membrane currents must be considered. (J Cardiovasc Electrophysiol, Vol. 14, pp. 651‐658, June 2003)
Usefulness of a New Radiofrequency Thermal Balloon Catheter for Pulmonary Vein Isolation:
Authors: Satake Shutaro , Tanaka Kazushi , Saito Shigeru , Tanaka Shinji , Sohara HiroshI , Hiroe Yoshitaka , Miyashita Yusuke , Takahashi Saeko , Murakami Masato , Watanabe Yoshio
Published: June 2003

Introduction: A rapidly firing or triggered ectopic focus located within a pulmonary vein (PV) or close to the PV ostium could induce atrial fibrillation (AF). The aim of this study was to evaluate the efficacy and safety of a radiofrequency thermal balloon catheter for isolation of the PV from the left atrium (LA).

Methods and Results: Twenty patients with drug‐resistant paroxysmal AF were treated by isolating the superior PVs using an RF thermal balloon catheter. Using a transseptal approach, the balloon, which had an inflated diameter 5 to 10 mm larger than that of the PV ostium, was wedged at the LA‐PV junction. It was heated by a very‐high‐frequency current (13.56 MHZ) applied to the coil electrode inside the balloon for 2 to 3 minutes, and the procedure was repeated up to four times. The balloon center temperature was maintained at 60° to 75°C by regulating generator output. Successful PV isolation was achieved in 19 of the 20 left superior PVs and in all 20 of the right superior PVs and was associated with a decrease in amplitude of the ostial potentials. Total procedure time was

1.8 ± 0.5

hours, which included

22 ± 7

minutes of fluoroscopy time. After a follow‐up period of

8.1 ± 0.8

months, 17 patients were free from AF, with 10 not taking any antiarrhythmic drugs and 7 taking the same antiarrhythmic agent as before ablation. Electron beam computed tomography revealed no complications, such as PV stenosis at ablation sites.

Conclusion: The PV and its ostial region can be safely and quickly isolated from the LA by circumferential ablation around the PV ostia using a radiofrequency thermal balloon catheter for treatment of AF. (J Cardiovasc Electrophysiol, Vol. 14, pp. 609‐615, June 2003)