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[Functional electrical stimulation instead of surgery? Improvement of grasping function with FES in a patient with C5 tetraplegia].

The aim of this study was to restore the grasp function of a tetraplegic patient with a C5 spinal cord injury (SCI) by means of functional electrical stimulation (FES). Using three pairs of surface electrodes and orthotic wrist stabilisation a simple palmar grasp was realised. The FES was controlled with a switch mounted on a wheelchair or-for the first time-with an EEG-based brain-computer interface (BCI). Application of this stimulation system enabled the patient to drink for the first time after the accident from a glass without any additional help.

Activities of Daily Living↗

[Examination of psychological functions by functional imaging with positron emission tomography and magnetic resonance imaging].

Changes in regional cerebral blood flow (rCBF) during experimentally modified psychological activation can be measured using radioactive ligands with positron emission tomography (PET) and using magnetic resonance principles with functional magnetic resonance imaging (fMRI). With PET it is possible to determine not only rCBF, but also metabolic changes, as well as the density and binding of several neuroreceptors. This can be done in conjunction with psychological and pharmacological challenge. fMRI is an imaging technique for perfusion-based signal intensities of the brain which does not involve radioactivity and gives better anatomical and temporal resolution than PET. Under appropriate experimental conditions, subjects' behavior and experience can be modified while they are lying in a tomograph. These experiments can be used for the scientific investigation of cognitive constructs such as memory and attention, or emotional processes. In this review, both functional neuroimaging techniques are assessed.

Arousal↗

Functional and structural abnormalities in the nerves of type I diabetic baboons: aminoguanidine treatment does not improve nerve function.

AIMS/HYPOTHESIS: To improve understanding of the pathophysiology of diabetic neuropathy and to establish a primate model for experimental studies, we examined nerve changes in baboons with Type I (insulin-dependent) diabetes mellitus. We also examined the effect of aminoguanidine (an inhibitor of the formation of advanced glycation end products) on nerve function. METHODS: Male baboons (Papio hamadryas) were assigned to four groups; control, diabetic, control and diabetic treated with aminoguanidine. Diabetes was induced with streptozotocin (60 mg/kg, intravenous). Insulin and aminoguanidine (10 mg/kg) were injected subcutaneously daily. Motor and sensory nerve conduction velocity was measured using standard techniques. Autonomic function was examined by measuring heart rate response to positional change. Sural nerve morphometry was analysed in the diabetic group (mean duration 5.5 years) along with their age-matched controls. RESULTS: The diabetic groups were smaller in size with a mean HbA1c of 8.9 +/- 1.2%. The nerve conduction velocity and heart rate response was reduced in the diabetic groups. Morphometric analysis of the diabetic sural nerve showed smaller axon diameter (2.99 +/- 0.06 microns vs 3.29 +/- 0.06 microns; p < 0.01) accompanied by thinner myelin (1.02 +/- 0.02 microns vs 1.15 +/- 0.02 microns, p < 0.01) with no change in the axon density. Treatment with aminoguanidine for 3 years had no effect on glycaemic control and did not restore conduction velocity or autonomic dysfunction in the diabetic animals, contrary to the studies in rats. CONCLUSIONS/INTERPRETATION: These results show that the primate is a good model to study diabetic neuropathy and suggest that the accumulation of advanced glycation end products are not an early mechanism of nerve damage in this disorder.

Aging↗

Immediate and long-term results of ATG induction therapy for delayed graft function compared to conventional therapy for immediate graft function.

The use of polyclonal antibodies for delayed graft function (DGF) was tested in 83 renal allograft recipients. Conventional immunosuppression (CI) was given to 52 patients with immediate graft function (IGF) while 31 patients with DGF received the polyclonal antibody ATG. Administration of OKT3 was restricted to steroid-resistant acute rejections in both groups. The incidence and severity of acute rejections, graft survival rate, CMV infections, and lymphocyte subsets were examined. ATG patients experienced a total of 0.6 acute rejections per patient, whereas CI patients had 0.9 on the average (P < 0.05). Second and third acute rejections occurred less frequently and later in the ATG group than in the CI group (P < 0.01). Steroid-resistant acute rejections occurred in 20 of the CI patients (38 %) but in only 7 of ATG patients (23 %). One-year graft survival in the CI and ATG groups was 98.1% and 93.2%, respectively. A decreased CD4 + to CD8 + T-lymphocyte ratio of about 0.5 was still detectable 5 years after the initial ATG administration. Hence, patients with DGF appear to benefit from induction therapy with ATG.

Adult↗

Increased vasoconstrictor reactivity and decreased endothelial function in high grade varicocele; functional and morphological study.

The pathophysiology of human varicocele is not fully understood. We investigated vasoconstrictor reactivity, endothelial function and morphological changes in different grades of varicocele to clarify the pathophysiology. Contractile responses to phenylephrine, norepinephrine, serotonin and histamine were determined in isolated human varicose spermatic veins using the organ bath technique. Endothelial function was tested with acetylcholine-induced relaxation after phenylephrine-induced precontraction in the absence and presence of nitric oxide synthase inhibitor, L-NAME, and cyclooxygenase inhibitor, indomethacin. The cyclic guanosine monophosphate (cGMP) level was measured in the spermatic vein and peripheral plasma. Morphological changes were evaluated with light microscopy. Phenylephrine, norepinephrine, serotonin and histamine induced concentration-dependent contractions. The maximum contractions for all of these agents except norepinephrine were significantly higher in grade III than grade I and II (P<0.05). The sensitivity to phenylephrine was significantly higher in grades II and III than in grade I (P<0.05). In the presence of L-NAME and indomethacin, the difference from respective control phenylephrine-induced contractions was higher in grade I and II than grade III. Acetylcholine did not induce stable relaxation but the level of cGMP, which is responsible for the vasorelaxant effect of NO, in veins was lower in grades II and III than grade I (P<0.05). Vessel wall thickness increased in grade II and dilatation developed in grade III when compared to grade I (P<0.05). Our findings suggest that endothelium produces less vasorelaxant which results in the more enhanced effects of vasoconstrictor substances in grade III, indicating that endothelial dysfunction develops at high grades of varicocele.

Endothelium, Vascular↗

Impact of perioperative treatment of recombinant human growth hormone on cell immune function and intestinal barrier function: randomized, double-blind, controlled trial.

The objective of this study was to evaluate the effects of recombinant human growth hormone (GH) on cell immune function, intestinal barrier function, and outcome. A placebo-controlled randomized double-blind trial was performed, with 20 patients undergoing abdominal surgery enrolled in the study. The patients in the study group received GH (0.3 IU/kg/day) subcutaneously from day 3 before operation until day 7 after operation. The patients in the control group received placebo injections. All the patients were given isonitrogenic (0.15 g N/kg/day) and isocaloric (20 kcal/kg/day) parenteral nutrition from preoperative day 1 through postoperative day (POD) 6. The serum GH and insulin-like growth factor-1 (IGF-1) levels, intestinal permeability, peripheral CD4+/CD8+ lymphocyte subsets, and routine blood and biochemistry analyses were evaluated before and after GH treatment. In the study group a significant increase in serum levels of GH and IGF-1 was observed on PODs 3 and 7. A significant decrease in the CD4+ subset population and the CD4+/CD8+ ratio was observed in the control group on POD 7 compared with preoperative studies, whereas no change was observed in the study group. The lactulose/mannitol excretion (L/M) ratio in the control group was elevated significantly on POD 7 compared with that before operation ( p = 0.01), whereas the L/M ratio in the study group did not change compared to preoperative values ( p = 0.08). No adverse reactions were related to the administration. There were no differences observed in operation-related complications or postoperative hospital stays between the two groups. This small pilot study suggests that GH attenuated the depression in cellular immunity following surgical stress and possibly reduced the increase in intestinal permeability that occurs following operation. Further studies of a large group of patients are needed to determine if these changes can be translated into improved outcome in surgical patients.

Adult↗

Loss of functional capacity caused by a delayed onset of DMARD therapy in rheumatoid arthritis. Long-term follow-up results of the Keitel function test. Brief definite report.

The aim of this analysis was to investigate the impact of the postponement of DMARD therapy on the functional outcome of rheumatoid arthritis after 10 years of disease. 321 individuals with a disease duration of at least ten years were selected out of a cohort of more than 1800 patients. Two groups were analysed separately: patients who started DMARD therapy within the first year of their disease, and patients who received their first DMARD not earlier than five years after the onset of RA. The Keitel functional index was determined in every patient after 10 years of RA. After 10 years of disease, the swollen joint count and the ESR had decreased in both groups to a comparable degree. However, patients with early treatment performed significantly better in the Keitel test compared to the group with delayed therapy. Although patients with seropositive RA or rheumatoid nodules had a worse outcome in general, the benefit of early treatment was also significant in these subgroups.

Activities of Daily Living↗

Functional clusters in the human parietal cortex as revealed by an observer-independent meta-analysis of functional activation studies.

The human parietal cortex is a highly differentiated structure consisting of cytoarchitectonically defined subareas that are specifically connected with other cortical and subcortical areas. Based on evidence from neurophysiological studies in subhuman primates these subareas are supposed to be functionally highly specialized. Here, we reviewed 51 different neuroimaging studies on healthy subjects with activation of the parietal lobe in statistical parametric maps. Running a cluster analysis on the stereotactic coordinates of the centers of gravity of the activation areas and plotting them into Talairach space showed a high consistency of the mean activation foci for similar paradigms across different laboratories and functional imaging modalities. Our meta-analysis exposed seven distinct pairs of quite symmetrically distributed subareas of the parietal cortex of each hemisphere as well as three unpaired regions that are critically involved in the generation of limb and eye movements in egocentric and allocentric coordinates, but also in attention, memory and cognitive problem solving. These data highlights the modular organization of the human parietal lobe. By its locally interspersed distributed circuits it orchestrates specialized cognitive subfunctions interfacing perception and action. Our meta-analysis provides a new framework for understanding information processing in the human parietal cortex.

Brain Mapping↗

Adaptation of the Bath Ankylosing Spondylitis Functional Index to the Turkish population, its reliability and validity: functional assessment in AS.

The aim of this study was to adapt the Bath Ankylosing Spondylitis Functional Index (BASFI) to the Turkish population and investigate the reliability and the validity of the Turkish version. Seventy-six patients with ankylosing spondylitis (AS) were included in the study. The functional status of the patients was assessed by using the adapted Turkish version of the BASFI twice, at recruitment and 24 h later. For validity analysis, patients were also assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) evaluating disease activity, the Bath Ankylosing Spondylitis Global Score (BAS-G) indicating effect of the disease on patient's well-being, physician's assessment of the disease activity and pain intensity. Spinal mobility was assessed by the Bath Ankylosing Spondylitis Metrology Index (BASMI). Erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) levels of the patients were also recorded. The lumbar region and the sacroiliac joints were assessed by Stoke Ankylosing Spondylitis Spine Score (SASSS) and the hip joints were assessed by Bath Ankylosing Spondylitis Radiology Index hip (BASRI-h). The internal consistency was 0.89 (Cronbach's alpha), which showed a high reliability for the Turkish version of the BASFI. Test-retest reliability was good, with a high intraclass correlation coefficient between the two time points (ICC=0.93). Significant correlations were detected between the BASFI and the BASDAI, BAS-G, doctor's global assessment, and general pain intensity (r=0.62, p<0.001; r=0.47, p<0.001; r=0.55, p<0.001; r=0.47, p<0.001, respectively). The adaptation of the BASFI to the Turkish population was successful and it was found to be reliable and valid among Turkish patients. Thus, studies using the Turkish BASFI can be compared with international studies.

Adult↗

Private Speech and executive functioning among high-functioning children with autistic spectrum disorders.

Private speech used by high-functioning children with autistic spectrum disorders (ASD) (n = 33) during two executive functioning tasks was compared to that of typically developing children (n = 28), and children with ADHD (n = 21). Children with ASD were as likely as others to talk to themselves and their speech was similarly relevant and likely to appear in moments of task difficulty. Unlike others, children with ASD were more likely to get items correct when they were talking than when they were silent. Group differences in performance were observed when children were silent but not when children were talking. Findings suggest that autistic children talk to themselves in relevant ways during problem-solving and that such speech is helpful in normalizing their executive performance relative to controls.

Adolescent↗

A selfish function of a "social" gland? A postpharyngeal gland functions as a sex pheromone reservoir in males of the solitary wasp Philanthus triangulum.

The postpharyngeal gland (PPG) has long been assumed to be restricted to ants, where it mainly functions in the maintenance of social integrity. Recently, a PPG has been described in both sexes of a solitary digger wasp, the European beewolf, Philanthus triangulum (Hymenoptera, Crabronidae). Female beewolves use the contents of their PPG to embalm their honeybee prey to delay microbial growth. Here we show that in male beewolves, the PPG serves as a reservoir of the pheromone used to scent-mark their territories. Gas chromatography-mass spectrometry (GC-MS) analysis of PPG contents identified 55 substances including long-chain aliphatic hydrocarbons, and 13 substances with functional groups. The composition was consistent with the composition of the marking pheromone of male European beewolves described earlier. Comparisons of the PPG contents, and total-head extracts showed a strong congruency, suggesting that total-head extracts can be used for the analysis of marking secretion in beewolves. Furthermore, we found a dimorphism in the composition of the PPG contents, based on significant differences in the proportions of seven compounds between the two morphs.

Animals↗

Further evidence of noradrenergic regulation of rat hypothalamic estrogen receptor concentration: possible non-functional increase and functional decrease.

The regulation of estrogen receptors by the alpha 2-noradrenergic system was studied. A single injection of the alpha 2-noradrenergic antagonist, yohimbine, caused a biphasic effect on the concentration of cytosol estrogen receptors in the mediobasal hypothalamus and anterior pituitary gland. A short-latency increase was seen at 1.5-3 h, followed by a longer-lasting decrease at 8-16 h. Scatchard analysis revealed that the apparent, short-latency increase is in the concentration of binding sites, not in the affinity of the receptor for [3H]estradiol. The increase in the concentration of cytosol estrogen receptors is not blocked by pretreatment with the alpha 2-noradrenergic agonist, clonidine. In addition, no increase is detected in the concentration of cell nuclear estrogen receptors accumulating in response to a saturating dose of estradiol. Therefore, the apparent increase in the concentration of cytosol estrogen receptors may not represent a functional increase in receptors. The decrease in the concentration of estrogen receptors, which occurs 8-16 h after yohimbine treatment, is also seen after injection of the alpha 2-adrenergic antagonist, idazoxan, and is not due to a change in the in vitro rate of association of the receptors with [3H]estradiol. Furthermore, the decrease seems to be a functional decrease in the concentration of receptors capable of cell nuclear accumulation in response to estradiol injection, as indicated by the results of experiments in which the concentration of cell nuclear estrogen receptors was assayed after estradiol injection. These experiments provide further support for the hypothesis that the alpha-noradrenergic system, and perhaps specifically the alpha 2-subtype, is involved in decreasing the concentration of estrogen receptors in parts of the brain and pituitary gland. This interaction provides a mechanism by which the environment could regulate the sensitivity of certain neurons to estradiol. However, the finding that the initial increase in the concentration of cytosol estrogen receptors after yohimbine treatment is not followed by the predicted increase in cell nuclear estrogen receptors after estradiol injection raises questions about the physiological relevance of the apparent increase under some conditions.

Adrenergic alpha-Agonists↗

Functional heterogeneity of CD4-positive T-cell subsets: the correlation between effector functions and lymphokine secretion is limited.

Several effector functions and the lymphokine secretion pattern of 30 antigen-specific CD4+ T-cell clones have been investigated. The clones were generated directly by limiting dilution cloning of nylon wool-purified T-cells obtained from KLH immunized BALB/c mice and avoiding an initial bulk culture phase. Using this approach the CD4+ T-cell clones were grouped into helper and nonhelper subsets. Among the helper subset, clones which helped B-cells for specific antibody production by either cognate or noncognate recognition were identified. Some but not all of these helper clones fitted into the Th1 and Th2 scheme, if the lymphokine secretion pattern was evaluated. Among the nonhelper subset CD4+ clones which killed activated APC in a MHC class II-restricted and antigen-specific manner were identified. In addition, one clone which suppressed B-cell antibody production mediated by helper clones was found. However, neither the suppression of antibody responses nor the inability of the nonhelper clones to help B-cells is due to the killing of B-cells. Various attempts were made to convert nonhelper into helper clones and helper into killer clones, without success. Thus, the functional properties of these clones are stable traits and not convertible by varying the experimental conditions.

Animals↗

Functional preservation of the mammalian kidney. IV. Functional effects of perfusion with dimethyl sulfoxide (DMSO) at normothermia.

Rabbit kidney were perfused at 37degreesC with various concentrations of DMSO in a K+-Mg2+-rich perfusate. The effects of DMSO on various functional parameters of the rabbit kidney perfused for 60 min were compared with the functional effects of perfusion without DMSO under the same conditions. DMSO produced deviations in vascular resistance and perfusate flow rate from control values. In kidneys perfused with 1.4 and 2.8 M DMSO these vascular changes resulted in changes in GFR at relatively unchanged filtration fractions. The closely parallel relationship between changes in GFR and urine flow in all groups indicates that perfusion per se or perfusion with DMSO may shift the regulation of urine flow rate from tubular reabsorption, which obtains in the in vivo situation, to glomerular filtration. This view was supported by the relatively unchanged parameters of Na+ reabsorption and fractional water excretion during perfusion with all concentrations of DMSO. Additionally, DMSO perfusion resulted in significantly greater weight gains than those observed in kidneys perfused without DMSO, and significantly depressed clearances of PAH, with 2.1 and 2.8 M DMSO.

Animals↗

Recovery of function after spinal cord hemisection in newborn and adult rats: differential effects on reflex and locomotor function.

It is often assumed that the response of the immature nervous system to injury is more robust and exhibits greater anatomical reorganization and greater recovery of function than in the adult. In the present experiments the extent of recovery of function after spinal cord injury at birth or at maturity was assessed. We used a series of quantitative tests of motor behavior to measure reflex responses and triggered movements and to examine different components of locomotion. Rats received a midthoracic "over-hemisection" at birth or as adults. The neonatal operates were allowed to mature and the adult operates were allowed to recover. The animals were trained to walk on a treadmill and to cross runways of varying difficulty. The animals were tested for reflex responses and triggered movements, videotaped while crossing the runways, and footprinted while walking on the treadmill. The adult operates had greater deficits in the reflex responses than the neonatal operates. The adult operates lost the contact placing response and had a decreased hopping response in the ipsilateral limb, while these responses were not impaired in the neonatal operates. Although the contact placing response in the neonatal operates was spared, a greater stimulus was necessary to induce the response than in control animals. In contrast, the neonatal operates had greater deficits in locomotion. Footprint analysis revealed that the animals' base of support was significantly greater after the neonatal injury than after the adult injury, and deficits in limb rotation were larger in the neonatal operates than in the adult operates. Both groups crossed the grid with a similar number of steps but the adult operates made significantly more errors with the hindlimb ipsilateral to the lesion than the contralateral one, while the neonatal operates made an equivalent number of errors with both limbs. The neonatal operates took longer to execute the climb test and used a different movement pattern than the adult operates. The neonatal operates had a different locomotor pattern than the adult operates. Despite greater recovery of reflex responses after spinal cord injury at birth, the pattern of locomotion exhibits greater deficits when compared with the same lesion in the adult. Just as the anatomical consequences of injury to the developing nervous system are not uniform, similarly, the behavioral consequences are also not uniform. Spinal cord injury before the mature pattern of locomotion has developed results in a different motor strategy than after injury in the adult.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

The effect of ozone inhalation on metabolic functioning of vascular endothelium and on ventilatory function.

The primary purpose of this research was to determine the effect of ozone inhalation on pulmonary vascular endothelium. Male Fischer-344 rats were exposed to 0.5 or 0.7 ppm ozone, 20 hr/day for 7 days. Lungs were excised and perfused with Krebs medium containing [14C]serotonin or [14C]hippurylhistidylleucine (HHL). When compared to controls, the animals exposed to the lower ozone concentration showed no statistically significant changes in serotonin removal. In contrast, the higher ozone concentration resulted in a 32% decrease (p less than 0.0001) in serotonin removal, but had no effect on HHL. Rats similarly exposed to 0.7 ppm ozone but allowed to recover for 14 days in clean air showed no decrease in serotonin removal compared to their controls. Animals exposed sequentially to 0.5 ppm ozone for 7 days and then to 0.7 ppm for 7 days showed no alteration in serotonin metabolism, suggesting the development of tolerance initiated by the lower dose. After 7 days exposure to 0.7 ppm ozone, lung ventilatory function measurements revealed small though significant decreases in several parameters. Electron microscopic evaluation of lung capillary endothelium from animals exposed to the 0.7 ppm ozone showed no changes. Positive control animals exposed to greater than 95% oxygen, 20 hr/day for 2 days showed a 23% decrease in serotonin removal (p less than 0.03) and a 12% decrease in HHL removal (p less than 0.017). These studies indicate that inhalation of ozone can induce functional alterations in the lung endothelium, and that this effect occurs at a dosage of ozone that produces minimal ventilatory changes and no observable endothelial ultrastructural changes.

Administration, Inhalation↗

Functional studies on platelets of a patient with an acquired disorder of platelet function associated with autoantibodies against membrane glycoprotein IIB/IIIA complex.

Platelet functions have been studied of a 63 year old woman with a severe acquired thrombopathy. The platelets did not adhere to siliconized glass. Aggregation could not be induced by either ADP (1 microM) nor collagen (2 micrograms/ml), no release of serotonin was found under these conditions. Thrombin caused only a weak aggregation response. Quantitative analysis of platelet actin revealed a very low total actin content (473 micrograms/10(9) platelets) and an extremely low F-actin value (3% of total actin). Stimulation of platelets with 0.1 U/ml thrombin for 3 min resulted in an increase of only 5% F-actin, whereas ADP and collagen did not induce any actin polymerization. Ca2+ movement in the patient's platelets is severely impaired after ADP and collagen stimulation, whereas a normal Ca2+ movement was obtained by 0.1 U/ml thrombin. The inhibition of the functions of normal platelets (aggregation and actin polymerization) by addition of patient's serum (5-10% final concentration) points to receptor blockade by platelet autoantibodies in the patient's serum. The antibody was purified by adsorption on Protein-A-Sepharose. Addition of IgG-suspension (5% final concentration) to washed control platelets resulted in similar effects on aggregation and actin polymerization compared to the effects of patient's serum.

Actins↗

Functional and biochemical evidence for altered serotonergic function in the fawn-hooded rat strain.

Administration of various doses of DOI (a 5-HT2A/5-HT2C agonist) produced hyperthermia that was significantly less in the FH rat strain relative to the Wistar rat strain. Similarly, administration of various doses of ipsapirone (a 5-HT1A agonist) produced hypothermia that was significantly less in the FH rat strain relative to the Wistar rat strain. Furthermore, m-CPP (a 5-HT agonist)-induced increases in growth hormone levels were also significantly less in the FH rat strain relative to the Wistar rat strain. There was no significant difference in the levels of either 5-HT or 5-HIAA between the two rat strains in the frontal cortex, hippocampus, hypothalamus, and striatum. In the brain stem, however, both 5-HT and 5-HIAA levels were significantly lower in the FH rat strain relative to the Wistar rat strain. On the other hand, 5-HT turnover rate was significantly higher in the hypothalamus and striatum and significantly lower in the hippocampus in the FH rat strain relative to the Wistar rat strain. These findings provide further evidence for altered serotonergic function in the FH rat strain and, in addition, suggest that the FH rat strain may prove to be a useful genetic model for some neuropsychiatric disorders with possible abnormalities in serotonergic function such as depression, obsessive-compulsive disorder, and the eating disorders.

Amphetamines↗