bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reversible and irreversible nodal dysfunction in diabetic neuropathy
Authors: Brismar Tom , Sima Anders A. F. , Greene Douglas A. 
Published: January 2005

AbstractAcute reversible diabetic nerve dysfunction has been associated with a reversible myo‐inositol–related (Na+ + K+)‐ATPase defect, while poorly reversible chronic nerve dysfunction correlates with progressive axoglial dysjunction of peripheral nerve. The causal relationships between biochemical and neuroanatomical abnormalities and those of nodal membrane function are not known. Nodal clamp examinations were carried out in the sciatic nerve of diabetic BB‐rats to elucidate the events underlying diabetic nerve dysfunctions and how these relate to metabolic and structural defects of diabetic nerve. With increasing duration of diabetes, there was a progressive decline in nodal action potentials attributable to decreased Na+ permeability and a decrease in the membranous Na+ gradient. Vigorous insulin therapy in short‐term (6‐week) diabetic BB‐rats normalized the Na+‐permeability defect and the membranous Na+ gradient. These defects did not reverse in long‐term (24‐week) diabetic animals subjected to the same treatment. This poorly reversible nodal dysfunction accounts for the not readily reversible conduction defect in chronic diabetes and is probably directly related to irreversible axoglial dysjunction.
Disorders of the autonomic nervous system: Part 2. investigation and treatment
Authors: McLeod J. G. , Tuck R. R. 
Published: January 2005

AbstractAutonomic function may be adequately tested with noninvasive tests of sympathetic and parasympathetic pathways, including: the response of blood pressure to change in posture and isometric contraction, heart rate response to standing, variation in heart rate with respiration, Valsalva ratio, sweat tests, and plasma noradrenaline measurements. Abnormal results in two or more of these tests indicate autonomic dysfunction. Intraarterial catheterization and tests of vasomotor function are usually required only in doubtful cases or for research purposes. Treatment of autonomic dysfunction is focused primarily on bladder control and control of orthostatic hypotension. Orthostatic hypotension is best treated with physical measures, pharmacologically with 9‐alpha‐fluorohydrocortisone and dihydroergotamine mesylate. A number of other agents may be tried but results have been less effective.
Protective effects of liposome‐entrapped superoxide dismutase on posttraumatic brain edema
Authors: Chan Pak Hoo , Longar Susan , Fishman Robert A. 
Published: January 2005

AbstractOxygen‐derived free radicals and membrane lipid peroxidation have been postulated to be involved in brain edema and cell death, secondary to ischemia and traumatic injury. Using a model of brain edema induced by cold‐induced injury, we have demonstrated an early elevation of superoxide radicals followed by permeability changes in the blood‐‐brain barrier and development of edema in injured brain. Intravenous injection of liposome‐entrapped copper‐zinc‐‐superoxide dismutase 5 minutes before the injury‐enhanced entry of the enzyme into endothelial cells of the blood‐‐brain barrier of injured brain reduced the brain level of superoxide radicals and ameliorated blood‐‐brain barrier permeability changes and brain edema. Identical treatment 5 minutes after injury was also effective. These data demonstrate that superoxide radicals play an important role in the delayed development of vasogenic brain edema following brain injury.
Axilla skin biopsy: A reliable test for the diagnosis of Lafora's disease
Authors: Busard H. L. S. M. , GabreëLs‐Festen A. A. W. M. , Renier W. O. , Gabreës F. J. M. , Stadhouders A. M. 
Published: January 2005

AbstractSkin biopsies from the axilla were examined in 7 patients with clinical signs and symptoms of lafora's disease, in 9 relatives (7 parents and 2 siblings), and in 17 patients with chronic or progressive degenerative neurological disorders and chronic epilepsy, who served as controls. In the biopsies of all patients with Lafora's disease, typical periodic acid‐Schiff (PAS)‐positive inclusions were present in the myoepithelial cells of the secretory acini of the apocrine glands and/or in the cells of the eccrine duct. No abnormalities were found in the biopsies from relatives and controls. We conclude that axilla skin biopsy is an easy and reliable test for diagnosing Lafora's disease, and is preferable to liver biopsy, but has no value for carrier detection.
Multi‐center study of Parkinson mortality with early versus later dopa treatment
Authors: Diamond Shirley G. , Marchkham Charles H. , Hoehn Marchgaret M. , McDowell Fletcher H. , Muenter Manfred D. 
Published: January 2005

AbstractFour geographically diverse centers provided data on mortality in 359 patients with Parkinson's disease, the majority of whom began dopa treatment during the early experimental trials of 1968 to 1970. Patients were classified into three groups based on the duration of symptoms prior to starting dopa treatment: Group 1, 1 to 3 years; Group 2, 4 to 6 years; Group 3, 7 to 9 years. After 15 years of treatment and 3,689 person‐years of observation, Group 1 had an observed‐to‐expected mortality ratio of 1.43; Group 2,2.44; and Group 3, 2.95 (p < 0.05). This result confirmed that increased duration of disease was associated with increased mortality risk. To examine the effect of the time of initiation of dopa treatment, duration of disease was held constant at 17 years for all three groups. Observed‐to‐expected mortality ratios were 1.43 for Group 1; 2.66 for Group 2; 2.63 for Group 3. This statistically significant advantage for Group 1 (p < 0.0001) led to the conclusion that early treatment with dopa has a beneficial effect on life expectancy. After 17 years of disease, causes of death in Group 1 were less likely (p = 0.027) to be due to Parkinson's disease than was found in the other groups.
Muscle energy metabolism in human phosphofructokinase deficiency as recorded by 31P nuclear magnetic resonance spectroscopy
Authors: Argov Zohar , Bank William J. , Marchis John , Leigh John S. , Chance Britton 
Published: January 2005

Abstract31P nuclear magnetic resonance studies of a patient with phosphofructokinase deficiency in muscle provided the following new findings: First, ATP metabolism is disturbed at rest and during exercise. At rest, ATP levels are lower than normal and continue to decline during exercise. Second, exercise kinetics are normal, suggesting a normal mitochondrial fuel supply although glycolysis is blocked. Third, no “phosphate trapping” is observed during prolonged low‐level exercise. Fourth, postexercise recovery is abnormally prolonged by the slow dephosphorylation of sugar phosphates, which has an in vivo half‐life of about nine minutes. These findings demonstrate how musclé tissue adapts to a block in a major bioenergetic pathway.
Lambert‐Eaton myasthenic syndrome: I. Early morphological effects of IgG on the presynaptic membrane active zones
Authors: Fukuoka Tadahiro , Engel Andrew G. , Lang Bethan , Newsom‐Davis John , Prior Christopher , W.‐Wray Denis 
Published: January 2005

AbstractIn the freeze‐fractured presynaptic membrane of the motor end‐plate, the active zones consist of two parallel arrays and each array contains 10‐ to 12‐nm particles arranged in two rows. In the Lambert‐Eaton myasthenic syndrome (LEMS) and in mice treated with 10 mg/day of LEMS IgG, administered intraperitoneally for several weeks, there was a paucity and disorganization of the active zones, and clusters of 10‐ to 12‐nm particles appeared. To further define the changes in the active zones, mice were studied that had been treated over 2 days with 104 to 180 mg of IgG. Treatment transferred the physiological defect of LEMS. Control mice received normal human IgG or no IgG. The spacing and density (number/unit area) of active‐zone particles were evaluated in presynaptic membrane P‐faces using computer‐assisted stereometry. In the normal active zone, the distance between particles in a given row and between adjacent rows of an array was less than, but the distance between the two arrays was greater than, the distance between the two antigen‐binding sites on human IgG. In mice treated with LEMS IgG, the initial alteration in the active zone was a Decemberrease in the distance between particles in a given row and between adjacent rows of an array; the distance between the two arrays remained unaltered. In more affected active zones, the parallel orientation of the rows was disturbed and the arrays became clusters. There was a significantly reduced density of active zones and of large‐membrane particles associated with all active zones and clusters. The findings are consistent with the idea that LEMS IgG binds to the active‐zone particles, cross‐links these particles, and then modulates their density. This interpretation is in agreement with findings of the companion paper which follows in this issue of the Annals in which we immunolocalized LEMS IgG to the active zones at the motor end‐plates.
Acetylcholine receptors in human thymic myoid cells in situ: An immunohistological study
Authors: Schluep Myriam , Willcox Nicholas , Vincent Angela , Dhoot Gurtej K. , Newsom‐Davis John 
Published: January 2005

AbstractMyoid cells were studied by double immunofluorescence in sections of thymus from 47 patients with myasthenia gravis and 15 control subjects, using polyclonal sheep anti–troponin T and monoclonal antibodies to troponin I, striated muscle myosin, and acetylcholine receptor (AChR). The myoid cells were rare and located mainly in the medulla, and most were clearly positive for AChR; labeling was similar with four individual monoclonal antibodies specific for extrajunctional AChR and five that also recognize endplate AChR. They were mostly keratin‐positive and consistently HLA–DR–negative. In the myasthenia gravis samples, the myoid cells were similar but largely confined to medullary epithelial areas; AChR labeling was slightly weaker, but otherwise they did not differ noticeably from those of control subjects. A preliminary finding was of even rarer AChR‐positive/HLA‐DR–positive antigen‐presenting (possibly) cells seen in 9 of 9 myasthenia gravis samples and in none of 9 control samples. Although myoid‐cell AChR appears antigenically similar to extrajunctional muscle AChR, and must therefore express the epitopes that myasthenics' antibodies recognize, these cells do not appear to be foci of immunological stimulation in myasthenia gravis.
Trends in the incidence rates of stroke in Rochester, Minnesota, since 1935
Authors: Homer Daniel , Whisnant Jack P. , Schoenberg Bruce S. 
Published: January 2005

AbstractThe Mayo Clinic medical records system and records‐linkage system have been used to study trends in the incidence of stroke in Rochester, Minnesota, for comparison with U.S. stroke mortality trends. This study extends the observations back through 1935. The average annual incidence rate for the period 1935 to 1944 was 188 and 179 per 100,000 population for men and women, respectively—not significantly different from 200 for men and 178 for women for the period 1945 to 1954. The blood pressure level in these patients did not affect probability of survival or recurrent stroke. The trend in the incidence rate of stroke for women showed no change for the 20 years from 1935 to 1954, after which there was a gradual Decemberline. For men there was little change until 1969, after which there was a sharp Decemberline. We suggest that the gradual Decemberline in U.S. stroke mortality rates for this early period may include an artifact introduced by changing codes and changing fashions of diagnosis.
Photic cortical reflex myoclonus
Authors: Shibasaki Hiroshi , Neshige Ryuji 
Published: January 2005

AbstractThree patients with flash‐evoked myoclonus were studied electrophysiologically. Myoclonic jerks were elicited at a fixed latency after the application of photic stimuli and were always preceded at a fixed time interval by extremely enhanced cortical evoked potentials. The enhanced electroencephalographic (EEG) responses to flash were widely distributed over the scalp and were maximal at the central region; the occipital response preceded the frontocentral response by 3.4 to 5.1 msec. The interval from the frontocentral EEG response to the flash‐evoked myoclonus was similar to that from the giant somatosensory evoked potential to the electrically evoked myoclonus. Investigation of recovery of evoked cortical responses and of myoclonic jerks showed a period of extremely enhanced excitability of both central and peripheral phenomena following stimulus. All of these findings suggest a cortical reflex mechanism. The role of the occipital cortex in the pathogenesis of photic cortical reflex myoclonus remains to be elucidated.
Effects of oral physostigmine in Alzheimer's disease
Authors: Stern Yaakov , Sano Mary , Mayeux Richard 
Published: January 2005

AbstractPrevious studies of oral physostigmine in the treatment of Alzheimer's disease have: (1) assumed physostigmine is effective only in mildly affected patients; (2) relied on an initial “dose‐finding” phase to determine the most effective dose and excluded nonresponders; and (3) primarily assessed memory. We examined the response of 22 patients to six different daily dosages of oral physostigmine, using selective reminding tests that were administered twice daily. Nine patients had a “best” dose/day (mode = 13 mg/day), which was used in a subsequent double‐blind crossover study. The otehr 13 were given the highest tolerated dose. The selective reminding test and a full neuropsychological battery were given during the drug and placebo periods. As a group, the 22 patients improved significantly on the Wechsler Adult Intelligence Scale—Revised Digit Symbol subtest and a shape cancelation task (p < 0.05). Nine patients showed improved performance on the selective reminding test during physostigmine treatment, and 9 showed no response; 4 patients performed better during placebo treatment. Dose finding did not help in predicting response in the crossover study; only 2 of the 9 who showed improvement had a best dose. Dementia severity did not predict corssover response. This suggests that: (1) physostigmine as administered had no pronounced effect on memory in Alzheimer's disease; (2) oral physostigmine produces no greater benefits on memory in mildly than in moderately demented patients; (3) response in a dose‐finding phase does not predict response in double‐blind crossover; and (4) Digit Symbol and cancelation tasks may be more sensitive than memory tests to the effects of oral physostigmine.
Acute ischemia causes axonal stasis, swelling, attenuation, and secondary demyelination
Authors: Nukada Hitoshi , Dyck Peter James 
Published: January 2005

AbstractMicrosphere embolization of rat sciatic nerve capillaries results in a central fascicular ischemic core. Twenty‐four hours after microembolization, the pathological alterations along the length of 55 myelinated fibers were reconstructed by computer imaging of 2,000 serial semi‐thin epoxy sections of a tissue block that extended from just above and into an ischemic core. From proximal to distal, the typical sequence of pathological alternations was: normal → swollen dark axons + thin myelin or demyelination → attenuated axons → axon cytolysis (46 fibers) or normal axons (9 fibers). Because organelle accumulation and axonal swelling were the earliest and most proximal pathological lesions, we infer that regional hypoxia causes axonal stasis as a primary event. Demyelination was found in fibers showing swollen dark and attenuated axons. These findings suggest that axons are selectively vulnerable to acute ischemia and that, depending on severity, the fibers either undergo axonal degeneration or transitory structural alterations without axonal degeneration, the latter consisting of axonal changes and secondary demyelination.
Experimental hemiplegia in the monkey: Basal ganglia glucose activity during recovery
Authors: Gilman Sid , Dauth George W. , Frey Kirk A. , Penney John B. 
Published: January 2005

AbstractUnilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a dense contralateral hemiplegia that recovers partially with time. During the phase of dense hemiplegia, the local cerebral metabolic rate for glucose (lCMRGlc) is decreased significantly in the caudate nucleus, putamen, globus pallidus, subthalamic nucleus, substantia nigra, and red nucleus of the hemisphere ipsilateral to the lesion. In the present study, lCMRGlc in the basal ganglia was studied during the phase of partial recovery of motor activity. lCMRGlc was partially restored, and the greatest degree of restoration occurred in structures with direct connections to the cerebral cortex (caudate nucleus, putamen, subthalamic nucleus, substantia nigra, and red nucleus). Restoration was least in structures that do not receive direct connections from the cerebral cortex (the internal and external segments of the globus pallidus). The findings support the hypothesis that corticofugal activity accounts for a substantial degree of functional recovery.
Myelin‐associated glycoprotein in multiple sclerosis lesions: A quantitative and qualitative analysis
Authors: Möller Johanna R. , Yanagisawa Katsuhiko , Brady Roscoe O. , Tourtellotte Wallace W. , Quarles Richard H. 
Published: January 2005

AbstractMyelin‐associated glycoprotein (MAG), myelin basic protein (MBP), and proteolipid protein (PLP) were quantitated by immunoassays in nine plaque, inner periplaque, outer periplaque, and normal‐appearing white matter regions from brains of five multiple sclerosis patients and compared with the levels found in white matter samples of control subjects matched for age, postmortem time, and brain region. In plaque and inner periplaque regions, all three proteins were substantially reduced due to extensive myelin loss. In outer periplaque regions, MBP and PLP were close to control levels, but MAG was significantly reduced to a mean of 57% of control. All three proteins were close to control levels in the normal‐appearing white matter samples. MAG in the various regions was qualitatively examined on Western blots by binding of lectins and by immunostaining with polyclonal and monoclonal antibodies against carbohydrate and protein epitopes of MAG. Densitometric scanning of these blots did not reveal any qualitative differences in the oligosacharide or polypeptide moieties of MAG between samples from control subjects and those from multiple sclerosis patients. However, a high proportion of the MAG in the multiple sclerosis samples was often in the form of dMAG, a proteolytic derivative of MAG that is formed by a myelin‐associated, Ca2+‐activated, neutral protease. The preferential loss of MAG at the periphery of multiple sclerosis plaques may be initiated by its proteolytic conversion to dMAG.
Positron emission tomography study of human brain functional development
Authors: Chugani Harry T. , Phelps Michael E. , Mazziotta John C. 
Published: January 2005

AbstractFrom over 100 children studied with 2‐deoxy‐2{18F}fluoro‐D‐glucose and positron emission tomography we selected 29 children (aged 5 days to 15.1 years) who had suffered transient neurological events not significantly affecting normal neurodevelopment. These 29 children were reasonably representative of normal children and provided an otherwise unobtainable population in which to study developmental changes in local cerebral metabolic rates for glucose (lCMRGlc). In infants less than 5 weeks old lCMRGlc was highest in sensorimotor cortex, thalamus, brainstem, and cerebellar vermis. By 3 months, lCMRGlc had increased in parietal, temporal, and occipital cortices; basal ganglia; and cerebellar cortex. Frontal and dorsolateral occipital cortical regions displayed a maturational rise in lCMRGlc by approximately 6 to 8 months. Absolute values of lCMRGlc for various grey matter regions were low at birth (13 to 25 μmol/min/100 gm), and rapidly rose to reach adult values (19 to 33 μmol/min/100 gm) by 2 years. lCMRGlc continued to rise until, by 3 to 4 years, it reached values of 49 to 65 μmol/min/100 gm in most regions. These high rates were maintained until approximately 9 years, when they began to Decemberline, and reached adult rates again by the latter part of the second Decemberade. The highest increases of lCMRGlc over adult values occurred in cerebral cortical structures; lesser increases were seen in subcortical structures and in the cerebellum. This time course of lCMRGlc changes matches that describing the process of initial overproduction and subsequent elimination of excessive neurons, synapses, and dendritic spines known to occur in the developing brain. The determination of changing metabolic patterns accompanying normal brain development is a necessary prelude to the study of abnormal brain development with positron emission tomography.
On‐off phenomenon: Relation to levodopa pharmacokinetics and pharmacodynamics
Authors: Nutt John G. 
Published: January 2005

AbstractMotor function in the moderately to severely affected parkinsonian patient is critically dependent upon delivery of levodopa to the striatum. This, in turn, is influenced by the fluctuating plasma concentrations of levodopa produced by the drug's short half‐life and erratic absorption, and by modifiable transport at the blood‐brain barrier. Duration of response to a single dose of levodopa is proportional to peak plasma drug levels, and paradoxical responses may occur when plasma concentrations are in the vicinity of minimum effective concentrations. Thus the strategy of administering frequent, small doses of levodopa may contribute additional unpredictability to a fluctuating clinical response imposed by pharmacokinetic factors.
Differences in cerebral blood flow and glucose utilization in vegetative versus locked‐in patients
Authors: Levy David E. , Sidtis John J. , Rottenberg David A. , Jarden Jens O. , Strother Stephen C. , Dhawan Vijay , Ginos James Z. , Tramo Mark J. , Evans Alan C. , Plum Fred 
Published: January 2005

AbstractPositron emission tomographic studies of regional cerebral metabolic rate for glucose (rCMRGlc) and cerebral blood flow were performed in 7 vegetative and 3 locked‐in patients to determine objectively the level of brain function underlying these clinical states. Cortical gray rCMRGlc in the vegetative patients was 2.73 ± 0.13 (mean ± SEM) mg/100 gm/min, less than half the normal value of 6.82 ± 0.23 (p < 0.001). Cerebral blood flow exhibited similar but more variable reductions. By contrast, cortical rCMRGlc in the locked‐in patients was 5.08 ± 0.69, a 25% reduction (p < 0.02) from normal. The massive reduction in vegetative rCMRGlc involved not only the cerebral cortex but also the basal nuclei and cerebellum. Such metabolic hypoactivity has precedent only in deep anesthesia and supports clinical evidence that cerebral cognitive function is lost in the vegetative state, leaving a body that can no longer think or experience pain.