Responsiveness of the somatosensory system after nerve injury and amputation in the human hand

We studied the responsiveness of the somatosensory system in humans after prolonged deprivation of peripheral input. Eight patients with traumatic transection of the median or ulnar nerve and 6 patients with amputation of a finger or hand underwent microneurography and intraneural stimulation. Bundles of nerve fibers were electrically stimulated through a microelectrode placed in the affected nerve proximally to the site of damage or in the case of amputees, in a nerve fascicle supplying the stump. During intraneural stimulation the subjects with nerve injuries reported distinct percepts in the hypoesthetic skin. Their projections were usually confined to the territory of a single or two adjacent palmar digital nerves, similar to the fascicular territories of healthy nerves in control subjects, but there was much less microneurographically recordable afferent activity than in normal subjects. In amputees intraneural stimulation evoked sensations in a phantom digit or digits in over three fourths of the fascicles studied. We conclude that (1) the somatosensory system remains able to process information from a nerve fascicle that has lost its cutaneous territory, and (2) somatosensory localization remains accurate despite the presumed central reorganization that takes place after nerve division or amputation. This lack of functional adaptation has important implications with regard to our understanding of human central nervous system plasticity.     

Evaluation of the Transverse Sinus by Magnetic Resonance Venography: Limitations-An Illustrative Case Report

Many techniques of magnetic resonance angiography depend on flow velocity. The broad normal range of venous flow velocities and preferential patterns of drainage, particularly in the transverse sinuses, may produce images that are diagnostically misleading. This reports such a case, with samples of various flow patterns in the transverse sinuses of other individuals, as demonstrated by one magnetic resonance angiographic technique (time-of-flight).     

Mobilization and evolutionary history of miniature inverted-repeat transposable elements (MITEs) in Beta vulgaris L.

We have identified three families of miniature inverted-repeat transposable elements (VulMITEs) in the genome of sugar beet (Beta vulgaris L.), evidently derived from a member of the Vulmar family of mariner transposons. While VulMITEs I are typical stowaway-like MITEs, VulMITEs II and VulMITEs III are rearranged stowaway elements of increased size. The integration of divergent moderately and highly repetitive sequences into VulMITEs II and, in particular in VulMITEs III, respectively, shows that amplification of repetitive DNA by MITEs contribute to the increase of genome size with possible implications for plant genome evolution. Fluorescent in-situ hybridization (FISH), for the first time visualizing stowaway MITE distribution on plant chromosomes, revealed a dispersed localization of VulMITEs along all B. vulgaris chromosomes. Analysis of the flanking sequences identified a dispersed repeat as target site for the integration of the stowaway element VulMITE I. Recent transposition of VulMITE I, which most likely occurred during the domestication of cultivated beets, was concluded from insertional polymorphisms between different B. vulgaris cultivars and species. ^†Sequence data from this article have been deposited in the EMBL/GenBank Data Library under the accession nos. AM231630-AM231653 and AM259123-AM259125.     

Tumor targeting by an aptamer.

Aptamers are small oligonucleotides that are selected to bind tightly and specifically to a target molecule. We sought to determine whether aptamers have potential for in vivo delivery of radioisotopes or cytotoxic agents. METHODS: TTA1, an aptamer to the extracellular matrix protein tenascin-C, was prepared in fluorescent and radiolabeled forms. After in vivo administration, uptake and tumor distribution of Rhodamine Red-X-labeled aptamer was studied by fluorescence microscopy. In glioblastoma (U251) and breast cancer (MDA-MB-435) tumor xenografts, biodistribution and imaging studies were performed using TTA1 radiolabeled with (99m)Tc. Tenascin-C levels and tumor uptake were studied in a variety of additional human tumor xenografts. To assess the effect of radiometal chelate on biodistribution, mercapto-acetyl diglycine (MAG(2)) was compared with diethylenetriaminepentaacetic acid and with MAG(2)-3,400-molecular-weight PEG (PEG(3,400)). RESULTS: Intravenous injection of fluorescent aptamer TTA1 produced bright perivascular fluorescence in a xenografted human tumor within 10 min. In the ensuing 3 h, fluorescence diffused throughout the tumor. Labeled with (99m)Tc, TTA1 displayed rapid blood clearance, a half-life of less than 2 min, and rapid tumor penetration: 6% injected dose (%ID)/g at 10 min. Tumor retention was durable, with 2.7 %ID/g at 60 min and a long-lived phase that stabilized at 1 %ID/g. Rapid tumor uptake and blood clearance yielded a tumor-to-blood ratio of 50 within 3 h. Both renal and hepatic clearance pathways were observed. Using the (99m)Tc-labeled aptamer, images of glioblastoma and breast tumors were obtained by planar scintigraphy. Aptamer uptake, seen in several different human tumors, required the presence of the target protein, human tenascin-C. Modification of the MAG(2) radiometal chelator dramatically altered the uptake and clearance patterns. CONCLUSION: TTA1 is taken up by a variety of solid tumors including breast, glioblastoma, lung, and colon. Rapid uptake by tumors and rapid clearance from the blood and other nontarget tissues enables clear tumor imaging. As synthetic molecules, aptamers are readily modified in a site-specific manner. A variety of aptamer conjugates accumulate in tumors, suggesting imaging and potentially therapeutic applications.     

Socioeconomic position and variations in coping strategies in musculoskeletal pain: a cross-sectional study of 1,287 40- and 50-year-old men and women.

OBJECTIVE: To examine the association between socioeconomic position and coping strategies in musculoskeletal pain. DESIGN AND SUBJECTS: Cross-sectional study of a random sample of 40- and 50-year-old Danes, participation rate 69%, n=7,125. The study included 1,287 persons who reported functional limitations due to musculoskeletal pain. METHODS: Data was collected by postal questionnaires and scales were developed on problem-solving coping and avoidant coping, based on a range of preliminary studies. Multivariate logistic regression analyses was used to study the correlation with socioeconomic position, measured by occupational social class. RESULTS: Among women, there was no correlation between social class and avoidant coping, but a significant decrease in the use of problem-solving coping by decreasing social class, adjusted odds ratio (OR) = 2.64 (95% confidence interval (CI) 1.31-5.32) in social class V vs social classes I + II. Among men, there was no correlation between social class and problem-solving coping, but a significant increase in the use of avoidant coping with decreasing social class, adjusted OR = 3.31 (95% CI 1.75-6.25) in V vs I + II. CONCLUSION: It is important for clinicians who advise and support patients in their response to musculoskeletal pain to be aware of socioeconomic differences in coping strategies. Gender differences in the association between socioeconomic factors and coping should be further investigated.     

Antisocial behavior of intravenous drug abusers: implications for diagnosis of antisocial personality disorder.

OBJECTIVE: A pattern of chronic adult antisocial behavior is not sufficient for the DSM-III-R diagnosis of antisocial personality disorder unless the early-onset criteria are satisfied, even if the adult criteria are met. The utility of the early-onset requirement for the diagnosis was examined in intravenous drug abusers, a population known to have high rates of irresponsible, aggressive, and criminal behavior. METHOD: The subjects were 237 drug abusers who had volunteered for an outpatient study of psychopathology and HIV risk behavior and infection. They completed a structured psychiatric interview as part of their participation in that study. The adult antisocial behavior of the group that met both the early-onset and the adult criteria for antisocial personality disorder, the group that met only the adult criteria, and the group that met neither the early-onset nor the adult criteria was then compared. RESULTS: Antisocial personality disorder (meeting the early-onset and adult criteria) was diagnosed in 44% of the sample; an additional 24% met only the adult criteria. The group with the diagnosis of antisocial personality disorder reported a more pervasive and more serious pattern of adult antisocial behavior than did the other groups, although antisocial behavior was commonplace in all three groups. CONCLUSIONS: Early onset of multiple antisocial behaviors identified a subset of drug abusers with important differences in the extent and severity of their adult antisocial behavior. The antisocial behavior of the group that met only the adult criteria suggests the possibility of a late-onset and less severe form of antisocial personality disorder.     

How much do 'attention' tests tell us?

Twelve measures commonly used to assess attentional processes were examined in a sample of 120 outpatients referred for neuropsychological evaluation. A single factor solution emerged. A second analysis partially replicated factors derived by Shum. McFarland, Bain, and Humphreys (1990). Classification rates (impaired vs. unimpaired) for the measures are presented. The implications of these findings for clinical assessment of attention are discussed     

Pharmacokinetics of isometronidazole. Basic model and estimation of the kinetic parameters from experimental data.

For the optimal timing of application of radiosensitizers in a course of radiotherapy it is important to know the sensitizer concentration at the time of irradiation. We have studied the pharmacokinetics of the hypoxic cell sensitizer isometronidazole in man and mouse and analyzed the data on the basis of an open two-compartment model after extravasal application. The parameter estimation is performed directly to avoid estimation biasing and data points from blood and tissue compartments are approximated simultaneously. The values obtained differ significantly from the estimations calculated by other authors for the same data.     

Differential behavioural and neurochemical effects of competitive and non-competitive NMDA receptor antagonists in rats.

The behavioural and biochemical effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, dizocilpine and memantine, and the competitive NMDA receptor antagonist, CGP 39551, were investigated in rats. Systemic injections of dizocilpine (0.33 mg/kg) increased locomotion and rearing in an open field, whereas memantine (20 mg/kg) increased only locomotor activity. CGP 39551 (10 and 20 mg/kg) did not change open field activity. Dopamine (DA) metabolism--as measured by the ratio of dihydroxyphenylacetic acid/dopamine (DOPAC/DA)--increased in response to dizocilpine in the prefrontal cortex and the nucleus accumbens. Memantine enhanced DOPAC/DA in the prefrontal cortex, the nucleus accumbens and to a lesser degree in the posterior striatum. In contrast to non-competitive NMDA receptor antagonists, CGP 39551 did not increase DA metabolism of subcortical structures and even decreased DOPAC/DA in the prefrontal cortex. These results indicate that competitive and non-competitive NMDA receptor antagonists affect spontaneous locomotion differentially in rats. The biochemical data imply that the stimulant actions non-competitive NMDA receptor antagonists are at least partially due to activation of ascending dopaminergic systems. Potential mechanisms involved in the differential effects of both types of NMDA receptor antagonists are discussed.     

Distribution of the nuclear thyroid-hormone receptor in extraocular and skeletal muscles.

The correlation between the occurrence of Graves' ophthalmopathy and Graves' hyperthyroidism may indicate a role for tri-iodothyronine (T3) hormone in the pathogenesis of Graves' ophthalmopathy. In Graves' ophthalmopathy the recti eye muscles are greatly enlarged whereas skeletal muscles seem unaffected. The distribution of the nuclear T3 receptor was studied in normal human and rat eye and skeletal muscles with immunohistochemistry using mouse (monoclonal) antibodies, and by in-situ hybridization for the detection of mRNA encoding the T3-receptor protein. Nuclear staining with T3-receptor antibodies was found in all types of tissues studied. Cytoplasmic staining occurred predominantly in the muscle fibres of the orbital layer of the eye muscles and was generally absent or very low in skeletal muscle fibres and hepatocytes. Immunostaining could be inhibited by preabsorbing the antibodies with bacterially expressed T3-receptor protein, implying specificity. The presence of nuclear and cytoplasmic hormone-free T3 receptor sites was indicated after preincubation of sections with T3 hormone; T3-receptor immunostaining decreased and T3-hormone staining increased. In-situ hybridization clearly revealed the presence of alpha-1 and beta-1 forms of the T3-receptor mRNA in liver, skeletal muscles, and orbital and intermediate layers of the eye muscles. The data demonstrate the presence of T3 hormone-receptor molecules in the extraocular and skeletal muscles. The different susceptibilities of these muscles to Graves' hyperthyroidism may relate to the quantitative differences in T3 hormone-receptor distribution.