bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying agonistic and antagonistic mechanisms operative at the GABA receptor
Authors: Galvez‐Ruano E. , Aprison M. H. , Robertson D. H. , Lipkowitz K. B.
Published: January 2005

Based on our molecular modeling investigations of the glycinergic receptor, we expanded our studies to similarly investigate the GABAergic receptor. New data suggest there may exist a slightly different agonistic mechanism for the molecules described herein as compared to glycine. The origin of this is undoubtedly the fact that, while glycine has a positive and two negative binding sites, it is significantly shorter than GABA and the other GABA agonists. Clearly, discovery of more glycine agonists is needed to further clarify this point. Moreover, we find a remarkedly different antagonistic mechanism exists for this phylogenetically newer inhibitory system in the central ncrvous system (CNS) than recently reported for strychnine and eight weaker glycine antagonists. We used GABA and six agonists (muscimol, dihydromuscimol, TRIP, isoguvacine, trans‐3‐aminocyclopentane‐1‐carboxylic acid, piperidine‐4‐sulfonic acid) and five antagonists (bicuculline‐Nl5‐rnethobromide, R5135, pitrazepin, iso‐THAZ and securinine) to derive our conclusions. We found that each of the agonists have three clearly defined atoms that can serve as attachment points at the GABAA receptor site. One of the three attachment atoms includes a carbonyl or carboxylate oxygen. The role of the carbonyl or carboxylate atom is very important. First, we theorize that a rapid two‐point attachment occurs (one from the positive end and one from one of the other two negative atoms on the ligand) at the recognition site in the receptor where GABA or a GABAergic agonistt binds. The positive end of the agonist perhaps associates through hydrogen bonding to a β‐carboxyl group in one of the aspartate molecules in the poly. peptide. The negative attachment points perhaps bind through hydrogen bonding to arginine molecules in this polypeptide. The second negative site in the agonist immediately triggers a conformational change by pulling together the aforementioned groups by electrostatic attraction, and hence opening the chloride channel. We propose the carbonyl oxygen is partly responsible for triggering the opening by formation of a double hydrogen bond to arginine. We postulate that this attraction is the first step inducing the conformational change. In the case of the GABA antagonists investigated, a fourth attachment site was not found. In fact only two sites have been identified similar to the group II glycine antagonists. Our data support a hypothesis for GABAergic antagonist activity which suggests that the antagonist simply binds to the recognition site and blocks the neurotransmitter, GABA, from entering this site thereby preventing the opening of the chloride channel; it just stays closed. This mechanism is different from the mechanism proposed for the large number of Group I glycine antagonists (Aprison et al.: J Neurosci Res 41:259‐269, 1995). © 1995 Wiley‐Liss, Inc.
Efficient and sustained transgene expression in mature rat oligodendrocytes in primary culture
Authors: Guo Z. , Yang N.‐S. , Jiao S. , Sun J. , Cheng L. , Wolff J. A. , Duncan I. D.
Published: January 2005

In order to evaluate the characteristics and efficiency of gene transfer in primary cultures of oligodendrocytes, four different techniques including particle bombardment (Accell® gene gun), cationic liposomemediated transfection (lipofection), calcium phosphate co‐precipitation and retroviral infection were compared using the LacZ and luciferase reporter genes. Highly purified postnatal adult rat oligodendrocytes were obtained by sequential immunopanning, plated in culture, and transfected using various reporter and promoter genes. The most efficient expression of LacZ and luciferase genes was found with particle mediated gene delivery. The transgene expression level obtained with gene gun delivery was at least two‐ to 100‐fold greater than three other tested gene transfer methods. Comparison of the relative strength of four viral and two cellular promoters in these primary oligodendrocytes cultures demonstrated that the CMV promoter was the strongest. Using a human growth hormone (hGH) reporter gene, a long‐term transgene expression pattern in primary oligodendrocytes was demonstrated to be sustained in culture for the entire experimental period (4 weeks) after particle‐mediated gene transfer. These results demonstrate that expression of a foreign gene can be effectively achieved ins primary cultures of adult oligodendrocytes, especially by using the particle bombardment method. The results also suggest that the current ex vivo gene transfer system may be used to manipulate oligodendrocytes for future application in gene therapy studies. © 1996 Wiley‐Liss, Inc.
Non-Heart-Beating Donor Porcine Livers: the Adverse Effect of Cooling
Authors: Reddy Srikanth , Greenwood Joanne , Maniakin Nikolai , Bhattacharjya Shantanu , Zilvetti Miguel , Brockmann Jens , James Tim , Pigott David , Friend Peter
Published: January 2005

Normothermic preservation has been shown to be advantageous in an experimental model of preservation of non-heart-beating donor (NHBD) livers, which have undergone significant warm ischemic injury. The logistics of clinical organ retrieval might dictate a period of cold preservation prior to warm perfusion. We have investigated the effects of a brief period of cold preservation on NHBD livers prior to normothermic preservation. Porcine livers were subjected to 60 minutes of warm ischaemia and then assigned to following groups: Group W (n = 5), normothermic preservation for 24 hours; and Group C (n = 6), cold preservation in University of Wisconsin solution for 1 hour followed by normothermic preservation for 23 hours (total preservation time, 24 hours). Synthetic function (bile production and factor V production) and cellular damage were compared on the

ex vivo

circuit during preservation. There was no significant difference in the synthetic function of the livers (bile production and factor V production). Markers of hepatocellular damage (alanine aminotransferase and aspartate aminotransferase release), sinusoidal endothelial cell dysfunction (hyaluronic acid), and Kupffer cell injury (β-galactosidase) were significantly higher in Group C. The histology of the livers at the end of perfusion was similar. In conclusion, a brief-period cold preservation prior to normothermic perfusion maintains the synthetic function and metabolic activity but results in significant hepatocellular damage, sinusoidal endothelial cell dysfunction, and Kupffer cell injury. Transplant studies are required to establish whether livers treated in this way are viable for transplantation.
Liver Transplantation in Hiv-Infected Recipients
Authors: Moreno Santiago , Fortún Jesús , Quereda Carmen , Moreno Ana , Pérez-Elías Ma Jesús , Martín-Dávila Pilar , de Vicente Emilio , Bárcena Rafael , Quijano Yolanda , García Miguel , Nuño Javier , Martínez Adolfo
Published: January 2005

Liver transplantation is being evaluated as a therapeutic option for human immunodeficiency virus (HIV)-infected patients with end-stage liver disease, but experience is still scarce. We describe the outcome of 4 HIV-infected patients who underwent liver transplantation in our hospital between July 2002 and April 2003. HIV-infected liver transplant recipients meet the same standard criteria for transplantation as do HIV-negative candidates. In addition, HIV infected persons are required to have a CD4 T-cell count greater than 100/mL (CD4 T-cells are targets for HIV infection). Immunosuppressive regimens, perioperative surgical prophylaxis, and prophylaxis for opportunistic infections are standard in the Liver Transplantation Unit in our hospital. Four patients, including 3 former intravenous drug users, received a liver transplant (2 from deceased donors and 2 from living donors), with a median follow-up of 510 days. Three patients (75%) are alive, with 1 death occurring 17 months posttransplantation in a patient who developed fibrosing cholestatic hepatitis. Rejection occurred in 1 patient, and was managed with no complications. Hepatitis C virus (HCV) recurrence occurred in 3 patients. HIV-infection has remained under control with antiretroviral treatment. A combination of 3 nucleoside analogs was used in 3 patients, with no need for drug adjustments. No opportunistic infections or other significant infectious complications developed. In conclusion, orthotopic liver transplantation seems a safe therapeutic option in the short term for HIV-infected persons with end stage liver disease, including patients with a history of drug abuse. If indicated, an antiretroviral regimen consisting of 3 nucleosides could be used to avoid interactions with immunosuppressive drugs.
Rapid Recurrence of Nonalcoholic Fatty Liver Disease After Transplantation in a Child With Hypopituitarism and Hepatopulmonary Syndrome
Authors: Jonas Maureen M. , Krawczuk Laura E. , Kim Heung Bae , Lillehei Craig , Perez-Atayde Antonio
Published: January 2005

Nonalcoholic fatty liver disease (NAFLD) has been reported in adults with hypothalamic or pituitary dysfunction, and some have progressed to end stage liver disease requiring transplantation. We report a teenager who intially presented with hypoxia due to intrapulmonary shunting, found to have NAFLD and cirrhosis associated with a hypothalamic tumor and panhypopituitarism. The NAFLD recurred very quickly after a successful liver transplant. Hepatopulmonary syndrome may be more common in cirrhosis associated with pituitary dysfunction than in other types of cirrhosis.
Menstrual‐related fluctuations in Parkinson's disease
Authors: Quinn Niall P. , Marsden C. David
Published: January 2005

Eleven of 12 premenopausal women with idiopathic Parkinson's disease recognised an increased severity of their symptoms for a few days before and during menstruation.
Individual manifestations of Parkinson's disease after ten or more years of levodopa
Authors: Klawans Harold L.
Published: January 2005

Twenty‐five consecutive patients with Parkinson's disease, who had been on levodopa for 10 or more years, were studied. Over the 12.9 years of treatment, the average Northwestern Disability Score had increased from 9.6 to 18.9. By this measure, 24 of 25 patients were worse, and one was unchanged. The progression of disability did not involve all pretreatment parkinsonian features equally in any of the patients studied. Instead a distinctive pattern of deterioration was seen: postural reflexes worsened in 24/25, speech in 24/25, and gait in 22/25. In contrast, rigidity was improved or unchanged in 17/25, tremor was improved or unchanged in 17/17, while handwriting was improved or unchanged in 21/22. Finger dexterity which was improved in 5/25, unchanged in 15/25, and worse in 5/25 which seemed to be between these two extremes. These observations demonstrate that some signs of parkinsonism can remain quite responsive to levodopa for more than 10 years while at the same time other manifestations of the disease are no longer as responsive to this form of treatment.
Clonidine in the treatment of essential tremor
Authors: Koller William , Herbster Gregory , Cone Sandra
Published: January 2005

The effect of clonidine treatment (average dose 0.4 mg/day) was investigated in 10 patients with essential tremor in a double‐blind placebo‐controlled design. Tremor amplitude and frequency were recorded with an accelerometer. Tremor was not significantly altered by clonidine therapy. Side effects were common. It is concluded that clonidine is not effective treatment for essential tremor.
Life‐threatening tardive dyskinesia caused by metoclopramide
Authors: Samie M. Reza , Dannenhoffer Mary Anne , Rozek Susan
Published: January 2005

A case of severe life‐threatening tardive dyskinesia resulting in esophageal and respiratory difficulties due to metoclopramide therapy is presented. A 66‐year‐old man with a primary diagnosis of clear cell carcinoma of the biliary duct was treated with metoclopramide for gastrointestinal symptons related to his chemotherapy regimen. The patients initially presented with tremor and rigidity in the upper extremities. On antiparkinsonian therapy, symptons progressed to hemiballism and involuntary movements of the face, mouth, and tongue, with respiratory and esophageal dyskinesia. Despite discontinuance of metoclopramide, severe tardive dyskinetic symptons resulted in placement of a gastrostomy tube to maintain nutritional support. This case along with other in the literature should emphasize the need for continuous reevaluation of metoclopramide during long‐term therapy, since serious side effects have been reported to occur.
Madopar HBS in fluctuating parkinsonian patients: Two‐year treatment
Authors: Pezzoli G. , Tesei S. , Ferrante C. , Cossutta E. , Zecchinelli A. , Scarlato G.
Published: January 2005

In an open‐label study, we substituted conventional levodopa plus benserazide: 100/25 (Madopar) with a controlled‐release form (HBS) in 18 fluctuating parkinsonian patients for 24 months. Significantly positive results were obtained in both peak‐dose and diphasic dyskinesias up to 12 months of treatment; morning akinesias were also improved up to 6 months. A general trend of deterioration, compared to the first 3–6 months of HBS treatment, was observed in “off” fluctuations after 1 year: akinesias due to a delayed response worsened after 1 year of treatment also when compared with the conventional treatment. Positive results were obtained with new HBS on standard Madopar‐related psychiatric disorders.
Meige syndrome: Neuropathology of a case
Authors: Kulisevsky J. , Marti M. J. , Ferrer I. , Tolosa E.
Published: January 2005

Primary Meige syndrome is a form of cranial dystonia of unknown cause. Only three postmortem studies have been reported, and the results of these studies have not been consistent. We have examined the brain of a 72‐year‐old man with typical primary Meige syndrome and found mild to moderate cell loss in the zona compacta of the substanita nigra, locus ceuleus, midbrain tectum, and dentate nucleus of the cerebellum. Also frequent lewy bodies were present in pigmented nuclei of the brainstem. No abnormalities were detected elsewhere. These pathological findings support the notion that brainstem pathology is important in the pathophysiology of cranial dystonia.
Epidemiology of focal and generalized dystonia in Rochester, Minnesota
Authors: Nutt John G. , Muenter Manfred D. , Aronson Arnold , Kurland Leonard T. , Melton L. Joseph
Published: January 2005

The epidemiology of generalized and focal dystonias was investigated in the Rochester, Minnesota, population over the period 1950–1982. The crude incidence of generalized dystonia was 2 per million persons per year, and for all focal dystonias combined, 24 per million per year. The crude prevalence rate was 34 per million persons for generalized dystonia and 295 per million persons for all focal dystonias. Torticollis was the most common focal dystonia; essential blepharospasm, oromandibular dystonia, spasmodic dysphonia, and writer's cramp were less common and had roughly equal incidence and prevalence rates.
Therapeutic trial with glycine in myoclonus
Authors: Truong Daniel Dung , Fahn Stanley
Published: January 2005

We investigated the therapeutic effects of glycine in seven patients with various forms of myoclonus. The initial phase was an open label trial. If benefit was seen in any patient, a double‐blind substitution of placebo was carried out to determine if the benefit was due, in fact, to glycine. The dosage of glycine was initiated at 600 mg/day and was increased gradually until a maximum dosage of 6,000 mg/day was reached. This dosage was maintained for at least 6 weeks before lack of efficacy was declared. No improvement was seen in four patients. One patient reported improvement, but he discontinued the drug because of adverse effects encountered with the use of a concomitant medication and before he could be tested in a double‐blind crossover phase. Two other patients also noticed improvement, but these improvements were not validated in the crossover phase. There were no adverse effects associated with glycine. Plasma glycine levels peaked at 30 min and returned to normal 1.5‐h after 1 g of glycine p.o. Cerebrospinal fluid (CSF) glycine levels did not change during treatment, suggesting inadequate penetration into the central nervous system of glycine at the dosage used.
Blepharoclonus provoked by voluntary eye closure
Authors: Behrman Simon , Scott D. F.
Published: January 2005

A patient of 23 years of age is presented who, on recovery following a severe head injury, developed abnormal involuntary movements of the eyelids. This consisted of intermittent blepharoclonus which recurred repetitively on voluntary, but not forced, eye closure. The possible genesis of this disorder will be discussed.
HLA antigens in drug‐induced parkinsonism
Authors: Metzer W. Steven , Newton Joseph E. O. , Steele Russell W. , Claybrook Marsha , Paige Stephen R. , McMillan Donald E. , Hays Sarah
Published: January 2005

The results of two epidemiological studies suggest a hereditary predisposition to develop drug‐induced parkinsonism. We investigated human leukocyte antigen (HLA) antigen prevalence rates in patients with neuroleptic‐induced parkinsonism. Fifty‐two male, white, neuroleptic‐treated, chronic inpatients with DSM‐III‐diagnosed schizophrenia were examined for the presence of parkinsonism. Subjects were tested for 23 type A, 43 type B, 4 type C, and 10 type DR HLA antigens. The group of schizophrenic patients with parkinsonism (n = 29) was compared with the group of schizophrenic patients without parkinsonism (n = 23). There were no significant differences between the two groups with respect to age, duration of neuroleptic exposure, or anticholinergic drug exposure. One HLA antigen, B44, was significantly more prevalent in the group with parkinsonism than in the group without parkinsonism. We derived a relative risk of 7.16 for drug‐induced parkinsonism with HLA‐B44 present in this group of schizophrenic patients. These data indicate that HLA‐B44 may play a role in genetic or immunologic susceptibility to develop drug‐induced parkinsonism in white schizophrenic individuals.
A case of post‐traumatic tic disorder
Authors: Singer Carlos , Sanchez‐Ramos Juan , Weiner William J.
Published: January 2005

We present the case of a 27‐year‐old man who developed multiple motor tics following closed head trauma with loss of consciousness. Age of onset, lack of family history of tics, and atypical progression of tic severity and location make it unlikely that the patient had Gilles de la Tourette syndrome. Previous reports of post‐traumatic tic syndrome are discussed.
Effect of intravenous injection of biperiden and clonazepam in dystonia
Authors: Povlsen Uffe Juul , Pakkenberg Henning
Published: January 2005

The acute effect of intravenous injections of biperiden and clonazepam was investigated in 14 patients with various forms of dystonia (segmental dystonia, 2; generalized dystonia, 6; and Meige's syndrome, 6). Eleven patients had primary dystonia, and 3 patients had a secondary form of dystonia. Doses of 5 mg of biperiden reduced dystonia when evaluated by total scores, global scores, and subjective scores. Two patients had marked side effects in the form of dizziness. Doses of 1 mg of clonazepam significantly reduced total scores and subjective scores, but the reduction in global score was insignificant. No patient had marked side effects following injection with clonazepam. These results correspond with earlier investigations of the longterm effects of anticholinergics and benzodiazepines. It is concluded that in some cases, intravenous injections can be used as a test for evaluating both effects and side effects of antidystonic medication prior to the institution of oral treatment. Long‐term intravenous treatment might be considered in individual cases.
Impaired habituation of long‐latency stretch reflexes of the wrist muscles in Huntington's disease
Authors: Abbruzzese G. , Dall'Agata D. , Morena M. , Spadavecchia L. , Rattod S. , Favale E.
Published: January 2005

Electromyographic responses to sudden wrist extension were recorded from the forearm and finger flexor muscles in 10 patients with Huntington's disease (HD) and in 10 normal controls. Stretch reflexes were characterized by a short‐latency (SL) and a long‐latency (LL) component both in patients and controls. Latency, duration, and size of the SL component were not different in the two groups, whereas the LL component was delayed in latency and reduced in size in HD patients. Increasing the stretch repetition rate from 0.1 to 0.4 cycles/s did not affect the SL component of either group, whereas the LL stretch reflex was reduced in size and duration in normal controls, but not in HD patients. These findings suggest an impairment of the “gain” mechanisms of the sole LL component, responsible for a desaturation of this component. This study supports the hypothesis that LL stretch reflexes are mediated by a transcortical long loop, possibly damaged in HD.
Sulpiride‐induced tardive dystonia
Authors: Miller Lucinda G. , Jankovic Joseph
Published: January 2005

Sulpiride is a selective D2‐receptor antagonist with antipsychotic and antidepressant properties. Although initially thought to be free of extrapyramidal side effects, sulpiride‐induced tardive dyskinesia and parkinsonism have been reported occasionally. We studied a 37‐year‐old man who developed persistent segmental dystonia within 2 months after starting sulpiride therapy. We could not find any previous reports of sulpiride‐induced tardive dystonia.
Hereditary essential myoclonus in a large norwegian family
Authors: Fahn Stanley , Sjaastad Ottar
Published: January 2005

We examined 56 members of a large Norwegian family with hereditary essential myoclonus, affecting mainly the neck and upper parts of the body, and inherited in an autosomal‐dominant pattern. We observed definite myoclonus in nine individuals, probable myoclonus in one, and possible myoclonus in one. There were two other living members who had a history compatible with myoclonus but who had developed a permanent remission, so we did not observe the movements, and two who had involuntary movements only with stress. Writing usually increased the myoclonus in the neck and trunk, but did not produce myoclonus in the arm used for writing. Having a conversation with an individual who was aware of being watched would also usually increase the myoclonus. Alcohol ameliorated the myoclonus in many, but not all, affected members. Activities such as walking and concentrating during reading would usually reduce the myoclonus. Three living members with definite myoclonus also had features of mild focal dystonia, either spasmodic torticollis or blepharospasm, indicating that focal dystonia may exist as part of the clinical spectrum in hereditary essential myoclonus. In addition to examining the members of the family, we videotaped them and obtained blood samples for molecular genetic analysis.
A double‐blind trial of isoniazid for essential tremor and other action tremors
Authors: Hallett Mark , Ravits John , Dubinsky Richard M. , Gillespie Marjorie M. , Moinfar Amir
Published: January 2005

We conducted a double‐blind trial of isoniazid in 11 patients with essential tremor and four patients with other types of postural action tremor. The tremor had not been helped by beta‐blockers or primidone. Isoniazid was given in doses up to 1, 200 mg daily, together with 100 mg pyridoxine, for four weeks. Results were assessed with subjective and objective scales. Only two patients with essential tremor appeared to benefit enough to continue the drug after the trial, and only one has benefited from its long‐term use. Isoniazid may be useful in rare cases of essential tremor, but must be monitored carefully because of its toxicity.
Kinetic‐dynamic relationship of oral levodopa: Possible biphasic response after sequential doses in Parkinson's disease
Authors: Contin Manuela , Riva Roberto , Martinelli Paolo , Baruzzi Agostino
Published: January 2005

The potential difference in the concentration‐effect relationship of oral sequential doses of levodopa was explored in six Parkinsonian patients with complex fluctuating response. These patients showed “wearing‐off phenomena” characterized by a transient worsening of motor function at the end of the first morning dose response to below baseline values and complained of a progressive reduction of levodopa effect during the day. A first standard levodopa dose was given in the morning, after an overnight fast and levodopa withdrawal. A second equal levodopa dose was administered immediately at the end of the first dose deterioration phase. Postimprovement worsening of motor response was also observed after the second levodopa dose in all patients. No significant difference in the pharmacokinetics of levodopa or in duration or magnitude of motor response could be appreciated between the two doses. These results further support the suggestion that, under controlled dietary conditions, plasma levodopa levels and effects relationship is reproducible between doses. Moreover, even when transient deterioration of motor function occurs between levodopa doses, the central dopaminergic system appears to remain responsive to the drug.
Movement Disorder in Down's syndrome: A possible marker of the severity of mental handicap
Authors: Haw Camilla M. , Barnes Thomas R. E. , Clark Kate , Crichton Paul , Kohen Dora
Published: January 2005

This study examined the nature and prevalence of abnormal movements in adults with Down's syndrome and also the clinical correlates of orofacial dyskinesia and the relationship between dyskinesia and the level of functional and intellectual disability. Movement disorder, language age, and disability were assessed in an epidemiologically based sample of 145 individuals with Down's syndrome. Abnormal involuntary movements were common, with >90% exhibiting dyskinesia, predominantly orofacial. Stereotypies were present in one‐third of the sample. There was an association between the severity of dyskinesia and both current language age and functioning in terms of self‐care and practical and academic skills, which suggested that dyskinesia may be a marker of the severity of mental handicap. The presence of dyskinesia was unrelated to neuroleptic exposure. Dyskinesia and stereotypies are very common in individuals with Down's syndrome and may represent an inherent manifestation of the disorder. The relationship between mental age and dyskinesia in Down's syndrome warrants further research.
The terminal innervation pattern in polymyositis: A histochemical and SFEMG study
Authors: Henriksson K‐G , Stålberg E.
Published: January 2005

Changes of the terminal innervation pattern in polymyositis were studied in nine patients using single fiber electromyography (SFEMG) and histochemical investigations of muscle biopsies. In all patients, and in 16 out of 18 muscles studied, reinnervation was found. The preceding denervation could be caused either by segmental necrosis of the muscle fiber that disconnects one part of the fiber from the end‐plate region or by direct intramuscular nerve involvement.
Myasthenia gravis: A personal view of pathogenesis and mechanism, part 1
Authors: Simpson John A.
Published: January 2005

A review of our current knowledge of the etiology and pathogenesis of myasthenia gravis is presented, with particular emphasis on the immunological aspects of the disease. Part 1, published in this issue, deals with the clinical and genetic features of myasthenia gravis which led to the autoimmune theory of the etiology of this disease. Various theories in this field are reviewed, and recent advances in our knowledge of the acetylcholine receptor protein, and its immunology, are examined. Part 2, which will appear in the March/April issue, provides a review of the dysfunction of physiology, pharmacology, and structure of the neuromuscular junction in myasthenia gravis, and the part played by the autoimmune process.
Effect of ethanol on lactic acid production by exercised normal muscle
Authors: Chui Luis A. , Munsat Theodore L. , Craig John R.
Published: January 2005

Several studies have suggested that muscle lactic acid production is defective in alcoholic myopathy. However, normal controls have not been evaluated. To study the effects of ethanol on the production of lactic acid in normal exercised muscle, oral ethanol (1 g per kg body weight, 20% v/v) was given to eight nonalcoholic subjects. Forearm ischemic exercise with a total work load of 7.2 kg‐m/min was performed just before and 90 min after ingestion of ethanol. At the time of exercise, the serum ethanol level was 95.7 ± 15.1 mg% (mean ± SD). Resting serum lactic acid was significantly higher after ingestion of ethanol (15.7 ± 4.5 mg%) than before (8.5 ± 4.7 mg%). Lactic acid generation with ischemic exercise was significantly lower after ethanol ingestion. The mean peak serum lactic acid level (expressed as percentage elevation above resting) was 330.5 ± 118.2% before and 127.9 ± 75.1% after (p <.05). These results indicate that a single oral dose of ethanol decreases lactic acid production by exercised muscle in normal subjects.
Sensory conduction studies in the early recognition of nerve disorders
Authors: Gilliatt R. W.
Published: January 2005

Early investigations into sensory conduction are reviewed and related to recent and ongoing research, specifically with relation to the early detection of nerve disorders. Current study on entrapment neuropathies and on the assessment of minor sensory conduction changes is presented. It is concluded that, in the early recognition of nerve disease, the clinical orientation of the electromyographer is essential to proper test interpretation.
Impaired regulation of the firing pattern of single motor units
Authors: Andreassen Steen , Rosenfalck Annelise
Published: January 2005

The firing pattern of single motor units from the anterior tibial muscle was studied during constant isometric contraction. Recordings were made with bipolar, fine‐wire electrodes from 4 normal subjects and from 10 patients with spasticity. A microcomputer was used to classify the motor unit potentials automatically and to measure the interspike intervals. The patients had reduced firing frequencies and reduced variability between neighbor intervals. Seven patients with spasticity due to supraspinal lesions had positive correlation between neighbor intervals.
F‐ and M‐wave conduction velocity in amyotrophic lateral sclerosis
Authors: Argyropoulos Constantine J. , Panayiotopoulos Chrysostomos P. , Scarpalezos Spyros
Published: January 2005

The F‐wave was used to estimate motor nerve conduction velocity (MNCV) along the proximal segment of the fastest axons of the deep peroneal nerve (anterior‐horn cells to knee) in 13 patients with amyotrophic lateral sclerosis (ALS) and in 21 age‐ and sex‐matched control subjects. Measurements were based on the shortest latency of 100 F‐waves obtained after supramaximal stimulation at the ankle and knee. The MNCV was estimated with the F‐wave and conventional M‐response methods in the distal segment (knee to ankle) of the nerve. Our results showed that proximal‐nerve conduction is faster than distal conduction both in control subjects and in ALS patients. In ALS, there was a moderate reduction of MNCV, which was of equal degree in both the proximal and distal segments of the deep peroneal nerve. In control subjects and in ALS patients, no statistically significant difference was found between the MNCV estimated for the knee‐to‐ankle segment by conventional means and that obtained by the F‐wave method. This indicates that the F‐wave of shortest latency is conducted by the fastest surviving motor fibers, as in the initial component of the M‐response–demonstrating that it is legitimate to make direct comparison of F‐ and M‐latencies in estimating the proximal MNCV.
Median neuropathy affecting the first dorsal interosseous muscle
Authors: Massey E. Wayne , Pleet A. Bernard
Published: January 2005

This case report documents the clinical entity of median nerve supply to the first dorsal interosseous muscle, which occurs in 3% of individuals. This must be remembered in evaluation of neuropathy involving the hand muscles.
Permeability of muscle spindle capillaries and capsule
Authors: Kennedy William R. , Yoon Kwon S.
Published: January 2005

The permeability of capillaries in rabbit muscle spindles, intramuscular nerves, and extrafusal muscle to intraaortically infused horseradish peroxidase (HRP) was studied. The permeability of the capsule cells of the muscle spindles was also examined. Immediately following the infusion of HRP, most extrafusal capillaries contained a dense accumulation of HRP reaction product, which began to escape into the surrounding extracellular space within 2–3 min. In contrast, the concentration of HRP in the intrafusal and endoneurial capillaries was much lower than that in extrafusal capillaries, and HRP was never found outside the former vessels. In addition, HRP never completely penetrated through the spindle capsule from the extracellular into the periaxial space, although it was regularly found between the outer two or three layers of capsule cells. The results indicate that the permeability characteristics of the muscle spindle capillaries and capsule to the tracer protein HRP are very similar to those of capillaries in peripheral nerve.
Animal models of alcoholic neuropathy: Morphologic, electrophysiologic, and biochemical findings
Authors: Bosch E. P. , Pelham R. W. , Rasool C. G. , Chatterjee A. , Lash R. W. , Brown L. , Munsat T. L. , Bradley W. G.
Published: January 2005

A chronic high alcohol intake was induced in rats through the use of two procedures: the schedule‐induced polydipsia technique and the liquid diet technique. Rats consumed 11–12 g of ethanol per kilogram body weight per day for 16 to 18 weeks. Morphologic evidence of a mild distal axonal neuropathy in the ventral caudal nerve was produced. The red blood cell transketolase levels were normal, indicating that the rats were not deficient in thiamine and suggesting that the axonal degeneration was due to the direct toxic effect of alcohol. Axonal transport studies demonstrated a significant increase in the amount of acetylcholinesterase transported in an orthograde direction in the sciatic nerves of alcohol‐exposed rats, and indicated no change in the transport of choline acetyltransferase or in the specific binding of colchicine by neurotubulin.
Neural hyperexcitability in hyperkalemic periodic paralysis
Authors: Segura Roberto P. , Petajan Jack H.
Published: January 2005

An electrophysiologic study of peripheral nerve excitability was performed in patients with hyperkalemic periodic paralysis (HPP) and in normal controls. It was found that a marked degree of neural hyperexcitability existed in all patients with HPP who showed cold sensitivity. The results suggest involvement of the nerve cell membrane in the proximal segments of peripheral nerve. This testing method may be of value in differentiating the cold‐sensitive variant of HPP.
Experimental corticosteroid myopathy: Effect on myofibrillar ATPase activity and protein degradation
Authors: Clark Abbot F. , Vignos Paul J.
Published: January 2005

Corticosteroid myopathy was studied in young, mature New Zealand white rabbits given daily injections of betamethasone (0.3 mg/kg body weight/day) for two weeks. Control rabbits were pair‐fed and received saline injections. Betamethasone treatment caused significant wasting of type 2 gluteus medius and psoas muscles but did not cause any atrophy of type 1 soleus and gluteus minimus muscles. The Mg2+‐ and Ca2+‐activated myofibrillar ATPase activities of the corticosteroid‐treated rabbits did not differ from controls despite a 30% reduction in muscle wet weight and pronounced reduction in cross‐sectional area of fibers. SDS‐polyacrylamide gel electrophoresis profiles of myofibrillar proteins did not differ quantitatively or qualitatively between experimental and control rabbits. Studies of net muscle protein degradation (using 3H‐leucine) in betamethasone‐treated and control rabbits indicate that both type 1 and type 2 muscle fiber proteins are degraded several times faster in the corticosteroid‐treated group. This suggests that a compensatory mechanism exists for those type 1 and mixed fiber type muscles which have increased degradation but do not undergo wasting.
Serum creatine kinase and pyruvate kinase in duchenne muscular dystrophy carrier detection
Authors: Percy Maire E. , Chang Lebe S. , Murphy E. Gordon , Oss Irina , Verellen‐Dumoulin Christine , Thompson Margaret W.
Published: January 2005

The incidence of elevated serum creatine kinase (CK) and pyruvate kinase (PK) activities was compared in 20 definite carriers of Duchenne muscular dystrophy (DMD), 47 possible carriers, and 42 female controls. When adult age was not regarded as a variable, 70% of the definite carriers had elevated PK, 55% had elevated CK, and 75% had elevated PK or elevated CK or both; 38% of the possible carriers had elevated PK, 19% had elevated CK, and 40% had elevated PK or elevated CK or both. The detection efficiency of the CK test was influenced by the age of the subjects: the upper normal limit of serum CK in the adult controls was at the minimum between 21 and 35 years of age, and CK activity in some carriers declined from elevated to normal levels with increasing age. With these considerations, 70% of definite carriers had elevated CK and 80% had elevated PK and/or CK; 34% of the possible carriers had elevated CK and 43% had elevated PK and/or CK. On the basis of the PK and CK measurements, only 16 of 24 possible carrier mothers were likely to be DMD carriers, implying that the other 8 were non‐carrier mothers of new mutant sons.
Split genes and muscular dystrophy
Authors: Lewis Robinson
Published: January 2005

Recent developments in molecular biology have shown that some genes are split into segments, each coding for part of a protein. The intervening segments are transcribed but later excised, and the messenger RNA is spliced back together again before translation into protein begins. Abnormalities in the nontranslated segments would not be reflected in abnormal protein structure but, presumably, in the control of synthesis of a particular protein. The muscular dystrophies may be an example of this class of disease. They are particularly amenable to investigation of this idea because muscle produces large amounts of relatively few proteins, facilitating isolation of the appropriate messenger RNA.
Evoked responses of the elbow flexors in control subjects and in myopathy patients
Authors: Krarup Christian , Horowitz Steven H.
Published: January 2005

Electrical and mechanical responses were evoked in the elbow flexors (EFs) of normal subjects and myopathy patients by maximal stimulation of the musculocutaneous nerve by a wire electrode in the axilla. In normals, the decrement in the mechanical responses during short trains of twitches was small (10%). The potentiation during a staircase decreased with increasing frequency of stimuli, but the potentiation 30 sec after the 100‐sec staircase was the same at all frequencies. Posttetanic potentiation was twice as large as the maximal potentiation attained during the staircase. The staircase phenomenon probably results from two opposing events, diminution and potentiation. Findings in 11 patients with myopathy varied according to the severity of involvement. Slight weakness of the EFs was associated with an increased twitch:tetanus ratio, decreased tetanic tension, and decreases in the staircase and posttetanic potentiation. Additionally, severe weakness of the EFs was associated with a diminution in twitch tension.
Animal models of peripheral neuropathy: The trembler mouse
Authors: McLeod J. G. , Low P. A.
Published: January 2005

One of the features of the IVth International Congress on Neuromuscular Diseases, held in Montreal September 17–21, 1978, was a series of invited posters. In order to achieve a wider audience for this valuable material, we have made arrangements to publish a number of these posters in Muscle & Nerve. This is the third poster in this series. To preserve the original effect of the posters, they are being reproduced almost exactly as they appeared at the Congress, without editing or other alterations. We hope you will find this feature a useful addition to your Journal.
Red blood cell and fibroblast membranes in Duchenne and myotonic muscular dystrophy
Authors: Roses Allen D. , Hartwig Geoffrey B. , Mabry Michael , Nagano Yasuho , Miller Sara E.
Published: January 2005

The literature concerning red blood cell and fibroblast protein studies in Duchenne and myotonic muscular dystrophy is critically reviewed. In this review, we emphasize methodological and technical considerations in order to promote an appreciation of the complexities of this area of research to clinical scientists interested in muscle disease.
Determinants of conduction velocity in myelinated nerve fibers
Authors: Waxman Stephen G.
Published: January 2005

This article reviews the determinants of conduction velocity in myelinated nerve fibers. For fibers exhibiting geometric similarity, conduction velocity is nearly proportional to diameter. However, in classes of geometrically similar fibers, myelin thickness and internode distance are linearly related to diameter. Therefore, it is not possible to assess the relative contributions of each of these factors. The relative effects of changes in each of these parameters on conduction velocity can be assessed from studies on fibers representing different similarity classes or from theoretical parametric studies. These studies show that for a fixed axon diameter, conduction velocity increases with myelin thickness. For a fixed total fiber diameter, there is an optimal ratio of axon diameter to total fiber diameter (and therefore to myelin thickness) at which conduction velocity is maximized. Conduction velocity is dependent on internode distance, with a broad maximum centered around the value observed in normal peripheral fibers. Conduction velocity is also dependent on temperature and the properties of the axonal milieu. Thus, the conduction speed of any given fiber reflects a number of parameters and is not determined by any single structural characteristic.
Centronuclear myopathy: Extraocular‐ and limb‐muscle findings in an adult
Authors: Bergen Barry J. , Carry Michael P. , Wilson W. Bruce , Barden Michael T. , Ringel Steven P.
Published: January 2005

Myotube‐like structures were seen in extraocular and limb muscles in an adult with centronuclear myopathy. The limb‐muscle fibers were very small and were of a uniform histochemical type. Extrajunctional acetylcholine receptors were not seen with immunoperoxidase stains, and ultrastructurally normal neuromuscular junctions were seen in the extraocular‐muscle samples. Further studies on developing muscle are needed to identify possible mechanisms of arrest of muscle maturation.
Congenital insensitivity to pain with anhidrosis
Authors: Rafel E. , Alberca R. , Bautista J. , Navarrete M. , Lazo J.
Published: January 2005

A nine‐year‐old child presented with congenital insensitivity to pain and anhidrosis. Quantitative studies and electron microscopy of the cutaneous branch of the radial nerve revealed almost complete absence of small myelinated and unmyelinated fibers and a disproportionate number of nerve fibers with a diameter of 6–10 μm. A grouping of both type 1 and type 2 muscle fibers was also seen. We suggest that this disease entity is not caused by a hereditary sensory neuropathy, but rather that it derives from a developmental defect.
Serum myoglobin in muscular dystrophy
Authors: Kagen Lawrence J. , Moussavi Shahla , Miller Stephanie L. , Tsairis Peter
Published: January 2005

Elevated levels of serum myoglobin (MGB) were found in patients with several types of myopathic disorders, namely, Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), facioscapulohumeral dystrophy, and limb‐girdle dystrophy. The frequency of hypermyoglobinemia was greatest in patients with DMD and BMD (91.7% and 100%, respectively). There was no precise direct relationship between serum creatine kinase (CK) and MGB levels, although the disorders with the highest CK levels tended to be the ones with the highest MGB levels. Among the patients with DMD, hypermyoglobinemia was slightly less marked in older children with restricted ability to walk than in the younger ones. Hypermyoglobinemia was noted among 43.8% of the mothers and 41.7% of the sisters of patients with DMD, slightly greater frequencies than for abnormal CK determinations in this group. Multiple serum samples were analyzed from 10 of these women, and the overall frequency of abnormal MGB levels was the same as that of abnormal CK levels; however, levels of CK and MGB were discrepant in some individual serum samples. For this reason, serum MGB determination may be a useful adjunct in the study of possible DMD carriers.
Echocardiography in duchenne muscular dystrophy
Authors: Danilowicz Delores , Rutkowski Monica , Myung Dong , Schievely Dora
Published: January 2005

The cardiac function of 36 males with Duchenne muscular dystrophy was evaluated by echocardiography, and the results were compared with the results of other tests of cardiac involvement, including serum creatine kinase isoenzyme evaluation, electrocardiography, chest x‐ray, and physical examination of the heart and lungs. Although correlation between the various methods of assessment was not impressive, the echocardiographic technique appeared to be useful in evaluating and following the cardiomyopathy in these patients. Several aspects of left ventricular function were abnormal in most patients, and only two of the 36 had normal left ventricular size and function. Electrocardiographic abnormalities were also apparent in all patients, although the changes were mild in four of the 36. Clinical evalution, isoenzyme determinations, and chest x‐rays have not been useful in assessing cardiac function. The echocardiographic data on these 36 patients are presented in detail and the patients will now be followed sequentially to attempt evaluation of ongoing changes.
Muscle reorganization after partial denervation and reinnervation
Authors: Peyronnard Jean‐Marie , Charron Louise
Published: January 2005

The normal rat tibialis anterior (TA) muscle was found to be innervated by approximately 154 spinal motor cells of which 95 are alpha motoneurons. Most of these axons ran in the L4 root and connected with glycolytic type 2B muscle fibers. The L5 root supplied 8.4% to 14.7% of the motor axons of TA muscle and innervated type 1 and 2A muscle fibers rich in oxidative enzymes. Two months after section of the peroneal nerve, there was marked fiber‐type grouping and compact rearrangement of the L4 and L5 motor units. After section of the L4 radicular nerve, the TA muscle remained atrophic with no evidence of fiber‐type grouping until 3 months when the L4 regenerating axons reached the muscle. Similar results were obtained after ligation of the divided ends of the L4 radicular nerve, which delayed but did not prevent reinnervation. These data suggest that, after partial denervation, muscle reinnervation by collateral sprouting is a slowly developing process.