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PubMed2000

G protein levels and function as an objective measure of depression in patients with functional bowel disorders.

Heterotrimeric G proteins play a pivotal role in postreceptor information transduction. These proteins have been implicated in the pathophysiology, diagnosis, and treatment of mood disorders and proposed as a state-dependent biochemical mood marker in mononuclear leukocytes. Irritable bowel syndrome (IBS) is associated with changes in mood, affecting patients' illness perceptions and behavior. We examined whether mononuclear leukocytes of patients with IBS have altered G protein measures. We undertook G protein functional measurements through agonist-enhanced [3H]Gpp(NH)p binding capacity and quantitative measures by immunoblot analysis using anti-Galpha antibodies in mononuclear leukocytes obtained from 19 IBS patients (Rome criteria) and 19 healthy matched subjects. The study groups were similar in age, gender, and years of education. Mononuclear leukocyte functions of G(s) (21.3+/-8.3%) and G(i) (22.2+/-6.7%) proteins in IBS patients were similar to healthy subjects (24.8+/-4.7 and 25.2+/-4.0%, respectively). The relative immunoreactivities of the G(sa) (98.9+/-10.2%) and the G(ia) (104.2+/-11.5%) subunit proteins in mononuclear leukocytes of IBS patients were also similar to those in healthy subjects. Two patients clinically diagnosed as depressed were detected by the G protein assay. The results lend objective support to the contention that major depression is not a causative factor in IBS, nor associated with its severity. The G protein assay may provide an objective biochemical tool for detecting depression in IBS, differentiating it from psychological distress that is commonly diagnosed by subjective tests.

Adult↗

PubMed2006

Aftertreatment of malleolar fractures following ORIF -- functional compared to protected functional in a vacuum-stabilized orthesis: a randomized controlled trial.

In a monocenter randomized controlled trial, 45 patients with isolated malleolar fracture type OTA/AO 44 A1-B2 undergoing ORIF were allocated randomly to a postoperative treatment either with a vacuum-stabilized orthesis with prescribed full weight bearing after the second week (23 patients) (orthesis group -- OG) or with functional aftertreatment with partial weight bearing of 15 kg for 6 weeks (22 patients) (control group -- CG). Outcomes were compared at 6- and 10-week follow-up examinations. The Olerud and Molander ankle (OMA) score, ankle swelling, usage of crutches, range of motion, Short Form 12, patient-reported visual analogue scales (VAS) (pain, comfort, walking confidence) and time to return to work were evaluated. All patients of OG showed reduced swelling at discharge. The median OMA scores after 6 weeks were 42 and 42.5 (p = 0.46) and after 10 weeks 69 and 72 (p = 0.55) in the OG and CG, respectively. The time to achieve secure walking capacity was reduced by 1 day (p = 0.03) in the OG. After ORIF of simple malleolar fractures, patients with a vacuum-stabilized orthesis can bear full weight 2 weeks postoperatively. This group experienced no adverse events. Postoperative swelling was significantly reduced and of the ability to walk on stairs confidently was shorter as compared to a functional aftertreatment without any external stabilization of the ankle.

Adolescent↗

PubMed1992

Delayed motor function and results of vestibular function tests in children with inner ear anomalies.

The relation between the results of vestibular function tests and gross motor development was examined in 4 children with inner ear anomalies. CT scans demonstrated the absence of lateral semicircular canals in both ears in all 4 cases. None responded to caloric stimulation using 40 ml of icewater. In contrast, the damped rotation test elicited per-rotatory nystagmus in all cases. Per-rotatory nystagmus was provoked in only two cases by the Bárány rotation test. Development of gross motor function, especially independent walking, was more delayed in the two children in whom the Bárány rotation test failed to elicit per-rotatory nystagmus.

Child↗

PubMed2006

Striatal function in generalized social phobia: a functional magnetic resonance imaging study.

BACKGROUND: Although evidence suggests the involvement of the amygdala in generalized social phobia (GSP), few studies have examined other neural regions. Clinical, preclinical, and dopamine receptor imaging studies demonstrating altered dopaminergic functioning in GSP suggest an association with striatal dysfunction. This is the first functional magnetic resonance imaging (fMRI) study to use a cognitive task known to involve the striatum to examine the neural correlates of GSP. We examined whether subjects with GSP had differential activation in striatal regions compared with healthy control subjects while engaged in a cognitive task that has been shown to activate striatal regions reliably. METHODS: Ten adult, unmedicated subjects with a primary DSM-IV diagnosis of GSP and 10 age-, gender-, and education-matched healthy comparison subjects underwent fMRI while performing the implicit sequence learning task. RESULTS: The GSP and healthy comparison subjects did not differ significantly on the behavioral performance of the task. Subjects with GSP, however, had significantly reduced neural activation related to implicit learning compared with healthy comparison subjects in the left caudate head, left inferior parietal lobe, and bilateral insula. CONCLUSIONS: These findings support the hypothesis that GSP is associated with striatal dysfunction and further the neurobiological understanding of this complex anxiety disorder.

Adult↗

PubMed2006

Abnormal endothelial function in female patients with hypothyroidism and borderline thyroid function.

BACKGROUND: It has been suggested that hypothyroidism is associated with an increased risk for cardiovascular disease. The aim of this study was to assess non-invasively NO-dependent endothelial function of resistance arteries in subjects with hypothyroidism of varying severity. METHODS: Ninety-six female subjects (aged: 42+/-13 years) comprised the study population. Subjects were divided into five groups based on TSH levels at presentation: Group 0 (n=23) with TSH: 0.3-2.0 microU/ml, Group 1 (n=22) with TSH: 2.1-4.0 microU/ml (upper normal), Group 2 (n=18) with TSH: 4.1-10 microU/ml (subclinical hypothyroidism), Group 3 (n=22) with TSH >10 microU/ml (overt hypothyroidism). One additional group with well-controlled hypothyroidism on L-thyroxine therapy (Group 4, n=11, TSH: 0.3-2.0 microU/ml) was also studied. Endothelial function of resistance arteries was assessed by measuring forearm blood flow response during reactive hyperemia utilizing venous occlusion strain-gauge plethysmography. RESULTS: Duration of reactive hyperemia was significantly different among groups of subjects with varying hypothyroidism (83.7+/-58.3 s, 53.2+/-35.7 s, 52.8+/-47.5 s, 12.9+/-13.3 s and 69.5+/-26.2 s in Groups 0, 1, 2, 3 and 4, respectively, p<0.001, ANOVA). Duration of reactive hyperemia was significantly shorter in subjects with upper normal TSH values (Group 1) compared to controls (53.2+/-35.7 s vs. 83.7+/-58.3 s, p=0.013), while it was comparable to that of subjects with subclinical hypothyroidism (Group 2) (52.8+/-47.5 s). However, duration of reactive hyperemia in Group 1 was significantly longer compared to Group 3 (overt hypothyroidism) (53.2+/-35.7 s vs. 12.9+/-13.3 s, p=0.002). Similarly, duration of reactive hyperemia in subjects with subclinical hypothyroidism was significantly longer compared to subjects with overt hypothyroidism (52.8+/-47.5 s vs. 12.9+/-13.3 s, p=0.003). Duration of reactive hyperemia in Group 4 (well-controlled hypothyroidism on L-thyroxine therapy) did not differ significantly compared to controls. There was a highly significant linear correlation between duration of reactive hyperemia and TSH (r=-0.383, p<0.001). CONCLUSION: Endothelial dysfunction was detected in the microvasculature of patients with hypothyroidism. Duration of reactive hyperemia decreased with increasing TSH levels. Since endothelial dysfunction is a factor leading to atherosclerosis, this abnormality may partly explain predisposition of patients with thyroid failure to cardiovascular disease.

Adult↗

PubMed2004

Functional connectivity in an fMRI working memory task in high-functioning autism.

An fMRI study was used to measure the brain activation of a group of adults with high-functioning autism compared to a Full Scale and Verbal IQ and age-matched control group during an n-back working memory task with letters. The behavioral results showed comparable performance, but the fMRI results suggested that the normal controls might use verbal codes to perform the task, while the adults with autism might use visual codes. The control group demonstrated more activation in the left than the right parietal regions, whereas the autism group showed more right lateralized activation in the prefrontal and parietal regions. The autism group also had more activation than the control group in the posterior regions including inferior temporal and occipital regions. The analysis of functional connectivity yielded similar patterns for the two groups with different hemispheric correlations. The temporal profile of the activity in the prefrontal regions was more correlated with the left parietal regions for the control group, whereas it was more correlated with the right parietal regions for the autism group.

Adult↗

PubMedDate not supplied

Renal transplants with delayed graft function show decreased renal function despite monitoring with postabsorptive levels.

Cyclosporine (CyA) monitoring with postabsorptive levels can predict the risk of an acute rejection episode (ARE). Large doses of CyA are needed to obtain adequate drug exposure. The impact of this strategy on renal function, especially in patients with delayed graft function (DGF), is unknown. We report our experience comparing C3 (3-hour postdose) monitoring with a historical series of cadaveric renal transplants. Sixty-three consecutive patients who received cadaveric renal transplants were followed for 1 year. Group A (historical n = 31) patients received 6 mg/kg/d CyA with the dose adjusted according to the trough level (target, 250-350 ng/mL), group B (study n = 32) received 10 mg/kg/d CyA with dose adjustments based upon C3 (target, 1100-1500 ng/mL). All patients received cyclosporine prednisone and a third agents. The general characteristics of the donors and recipients were comparable. The incidence of biopsy-proven ARE at 1 year in group A was 42% and 19% in group B (P <.05). Patients achieving C3 levels >1000 ng/mL at 1 week displayed significantly lower ARE rates (8% vs 50%; P <.05). The rate of DGF was similar in both groups, but the duration was longer in group B (15 vs 21 days, P <.05). The serum creatinine (SCr) level was significantly higher in group B at 3 months (1.47 mg/dL group A vs 1.76 mg/dL group B; P <.05). Patients in group B with DGF showed significantly higher SCr values at 1 year (1.18mg% vs 2.03 mg%; P <.05). C3 level monitoring of CyA yields excellent results in terms of decreased ARE, but an increased SCR was observed among patients with DGF.

Creatinine↗

PubMed2003

Thyroid function tests and neurocognitive functioning in children referred for attention deficit/hyperactivity disorder.

BACKGROUND: Thyroid abnormalities have been associated with attention deficit/hyperactivity disorder (ADHD) and with other childhood psychiatric disorders. The goal of this study was to determine the relationships between thyroid hormone concentrations, neurocognitive functioning, and psychiatric diagnosis in children. METHODS: Free thyroxine index (FT4I) and thyroid stimulating hormone (TSH) were obtained, along with diagnostic and descriptive information for 338 children referred to a clinic specializing in learning and behavior problems. RESULTS: Thyroid abnormalities were uncommon in children referred for ADHD. After excluding children with thyroid disease, there was a greater proportion with low concentrations of normal FT4I for ADHD-Predominantly Inattentive type (ratio=7.0), but not for ADHD-Combined Type. High concentrations of normal FT4I were associated with mood lability, preoccupations, and lower ratings of attention problems. Thyroxine concentrations within the normal range were differentially associated with ADHD-Combined Type compared to ADHD-Predominantly Inattentive, mood disorders, and pervasive developmental disorders. CONCLUSION: Thyroxine concentrations were associated with mood symptoms and unusual behaviors, and were less strongly related to attentional functioning. Thyroxine concentrations were not related to hyperactivity.

Adolescent↗

PubMedDate not supplied

Benoxaprofen suppression of polychlorinated biphenyl toxicity without alteration of mixed function oxidase function.

Polyhalogenated hydrocarbons are widely distributed environmental pollutants. Several members of the class, including certain polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans and dibenzodioxins, produce a characteristic toxicity syndrome, manifestations of which are increased mortality, oedema, hyperkeratosis, thymic involution and hepatotoxicity. The toxic hydrocarbons are also inducers of cytochrome P448-mediated mixed function oxidases. The toxicity and induction responses both involve initial binding of the hydrocarbon to the same cytosolic receptor, but the subsequent events are not understood. It is not known, for example, whether the toxicity and induction are causally related, or whether they are coordinated but independent aspects of a pleiotropic response. Here we report that benoxaprofen, a nonsteroidal antiinflammatory agent, decreases the toxicity of a PCB isomer, 3,4,3',4' tetrachlorobiphenyl (TCB), in the chick embryo and that it does so without altering the degree of mixed function oxidase induction. The independent alteration of PCB toxicity and induction suggests that the two phenomena are not causally related. The decrease in toxicity by benoxaprofen suggests further that products of arachidonic acid metabolism or other mediators of inflammation may have a causal role in halogenated hydrocarbon toxicity.

Animals↗

PubMed1999

Regulation of effector cell functions through the ligation of lymphocyte function-associated antigen-1 and intracellular adhesion molecule-1 leads to spontaneous regression of a rat histiocytoma.

Cell adhesion molecules mediate cell-to-cell interactions, thereby regulating effective immune response against target cells. We have investigated the intercellular cross-talk between lymphocyte function-associated antigen-1 (LFA-1) and its counter-receptor, intercellular adhesion molecule-1 (ICAM-1). This interaction regulates the postadhesion events leading to the regression of a rat histiocytoma, AK-5, which is mediated by natural killer (NK) cells through antibody-dependent cell cytotoxicity (ADCC). Repeated systemic administration of anti-cell adhesion molecule (anti-CAM) monoclonal antibodies (MoAbs), i.e. anti-LFA-1 and anti-intracellular adhesion molecule-1 (anti-ICAM-1), in AK-5 tumour-bearing animals enhanced tumour growth and caused delayed regression. The immune suppression achieved after the administration of these antibodies could be attributed to the diminished cytotoxic, as well as apoptotic, activity of NK cells. The MoAbs selectively reduced the adhesion of NK cells to the tumour cells in vitro. Flow cytometric analysis showed down-regulation of Fas-ligand expression on NK and T cells following MoAb administration in vivo. Marked reduction in the lymphokine-activated killer (LAK) activity of NK cells was also observed after in vitro blocking of LFA-1 and ICAM-1 molecules. In addition, continuous MoAb administration induced suppression of the cytokine response. These results underline the importance of ligand binding between LFA-1 and ICAM-1, which could provide co-stimulation for the effector-cell functions via signalling events to induce cytotoxicity, apoptosis and cytokine production, resulting in the efficient regression of AK-5 tumour in syngeneic hosts.

Animals↗

PubMed2001

Effects of left ventricular assist device on cardiac function: experimental study of relationship between pump flow and left ventricular diastolic function.

The left ventricular assist device (LVAD) with centrifugal pump has two characteristics. One is a pump flow wave of the centrifugal pump, consisting of the pulsatile flow of the native heart and the nonpulsatile flow of the centrifugal pump. The other is that the centrifugal pump fills from the native heart not only in the systolic phase, but also in the diastolic phase. In the case of the apex outlet LVAD with centrifugal pump, blood flows from the left atrium through the left ventricle to the pump. Pump flow is regulated by preload, and preload is regulated by diastolic hemodynamics. The aim of this study is to analyze the relationship between pump flow and the diastolic hemodynamics of the native heart. Ten anesthetized intact pigs were studied after placement of an LVAD. Data were recorded with the LVAD off (control) and the LVAD on. The assist rate was changed to 25%, 50%, and 75%. The indexes of left ventricular (LV) diastolic function included LV myocardial relaxation (time constant of isovolumic pressure decay [Tau] and maximum negative dP/dt [LV dP/dt min]) and LV filling (peak filling rate [PFR], time to peak filling rate [tPFR], and diastolic filling time [DFT]). Stroke volume decreased significantly in 75% assist. LV end-systolic pressure decreased significantly in 50% and 75% assist. LV end-diastolic volume decreased as assist rate increased, but there were no significant changes. Stroke work decreased significantly in 50% and 75% assist. LV dP/dt min decreased significantly in 50% and 75% assist. Tau prolonged as assist rate increased, but there were no significant changes. DFT shortened significantly in 75% assist. PFR increased significantly in 75% assist. tPFR shortened significantly in 50% and 75% assist. In this study, LV relaxation delayed as an increasing of pump assist rate, but it suggested a result of reduction of cardiac work. Also, it was suggested that LVAD increases the pressure difference between the left atrium and the left ventricle in the diastolic phase. This phenomenon is due to the filling of the left ventricle. In this study it was suggested that as pump assist rate increases, it is more effective to keep cardiac function in the diastolic phase.

Animals↗

PubMed2004

[Assessment of global and regional left ventricular function with a 16-slice spiral-CT using two different software tools for quantitative functional analysis and qualitative evaluation of wall motion changes in comparison with magnetic resonance imaging].

PURPOSE: To determine global and regional left ventricular (LV) function from retrospectively gated multidetector row computed tomography (CT) by using two different semiautomated analysis tools and to correlate the results with those of magnetic resonance imaging (MRI). MATERIALS AND METHODS: Nineteen patients (5 females, 14 males, mean age 69 years) underwent 16-slice spiral-CT (MS-CT) with standard technique without administration of beta-blockers for a decrease in the cardiac rate. Ten series of images were reconstructed at every 10 % of the RR-interval. With commercially available software capable of semiautomated contour detection, end-diastolic and end-systolic LV volumes (EDV and ESV) were determined from short-axis multiplanar CT reformations (MPR). Axial images of the end-systolic and end-diastolic cardiac phase were transformed to 3D volumes (3D) to determine EDV and ESV by using a threshold-supported reconstruction algorithm dependent on the contrast enhancement of the left ventricle. Steady-state free-precession cine MR images were acquired in short-axis orientation on the same day in all but one patient. Regional wall motion was assessed qualitatively in 17 left ventricular segments and classified as normo-, hypo-, a- or dyskinetic. Bland-Altman analysis was performed to calculate limits of agreement and systematic errors between CT and MRI. RESULTS: For MPR/3D, mean end-diastolic (144.4/142.8 mL +/- 67.5/67.1) and end-systolic (66.4/68.7 mL +/- 52.1/49.9) LV volumes as determined with MS-CT correlated well with MRI measurements (147.6 mL +/- 67.6 [ r = 0.98/0.96] and 73.3 mL +/- 55.5 [ r = 0.98/0.98], respectively [ p <.001]). LV stroke volume (77.6/74.1 +/- 19.2/23.4 mL for CT vs. 74.4 mL +/- 18.4 for MRI, r = 0.92/0.74) and LV ejection fraction (58.6/55.9 % +/- 13.5/13.7 for CT vs. 55.6 % +/- 13.5 for MRI, r = 0.95/0.91) also showed good correlation (p <.001). Regional wall motion analysis revealed agreement between CT and MRI in 316/323 (97.8 %) myocardial segments. CONCLUSION: Semiautomated analysis of 16-detector row CT data sets enables global and regional volumetric and functional analysis. The CT results correlate well with MRI findings for short axis MPR and for 3D volume reconstructions, with a higher statistical spread for the 3D method. The underestimation of end-systolic and end-diastolic volumes with CT may be caused by partial volume averaging due to the lower temporal resolution as compared with MRI.

Aged↗

PubMed2002

The Ultegra rapid platelet-function assay: comparison to standard platelet function assays in patients undergoing percutaneous coronary intervention with abciximab therapy.

BACKGROUND: Despite the proven benefit of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention, significant interpatient variability exists in antiplatelet response. Furthermore, a diminished degree of platelet inhibition is an independent predictor of adverse cardiac events, highlighting the need for accurate and precise monitoring of platelet function. METHODS: Patients (n = 192) who underwent elective percutaneous coronary intervention at 4 centers were enrolled. The following 3 time points were studied: 1, baseline, before abciximab bolus administration; 2, during, within 1 hour of abciximab bolus administration; and 3, post, 24 hours after abciximab bolus administration or at the time of patient discharge, whichever occurred first. The following 3 assays were compared at all time points: Ultegra rapid platelet-function assay (Ultegra RPFA), conventional turbidometric platelet aggregometry, and receptor binding assay with [125I]-abciximab. Variability in Ultegra RPFA measurements between operators was determined with performance of the assays at the point of care and in the laboratory. A sub-study of 22 patients at 1 center was performed in which the laboratory scientist performed all 3 assays in duplicate at each time point. RESULTS: Comparison with the receptor binding assay and conventional platelet aggregometry in 120 patients showed that the Ultegra RPFA correlated with aggregometry (r = 0.89) and with the receptor binding assay (r = 0.89). There was good agreement (r = 0.80) between values obtained by intended users and those obtained by laboratory scientists. Furthermore, Ultegra RPFA values had equivalent precision to the standard assays. CONCLUSION: The Ultegra RPFA has equivalent accuracy and precision when compared with the 2 reference assays studied. Ultegra RPFA measurements are not operator-dependent and are not influenced by concomitant medications, hematologic parameters, or demographics.

Abciximab↗

PubMed2000

Folding and function of I domain-deleted Mac-1 and lymphocyte function-associated antigen-1.

In those integrins that contain it, the I domain is a major ligand recognition site. The I domain is inserted between beta-sheets 2 and 3 of the predicted beta-propeller domain of the integrin alpha subunit. We deleted the I domain from the integrin alpha(M) and alpha(L) subunits to give I-less Mac-1 and lymphocyte function-associated antigen-1 (LFA-1), respectively. The I-less alpha(M) and alpha(L) subunits were expressed in association with the wild-type beta(2) subunit on the surface of transfected cells and bound to all the monoclonal antibodies mapped to the putative beta-propeller and C-terminal regions of the alpha(M) and alpha(L) subunits, suggesting that the folding of these domains is independent of the I domain. I-less Mac-1 bound to the ligands iC3b and factor X, but this binding was reduced compared with wild-type Mac-1. In contrast, I-less Mac-1 did not bind to fibrinogen or denatured bovine serum albumin. Binding to iC3b and factor X by I-less Mac-1 was inhibited by the function-blocking antibody CBRM1/32, which binds to the beta-propeller domain of the alpha(M) subunit. I-less LFA-1 did not bind its ligands intercellular adhesion molecule-1 and -3. Thus, the I domain is not essential for the folding, heterodimer formation, and surface expression of Mac-1 and LFA-1 and is required for binding to some ligands, but not others.

Animals↗

PubMed1997

Integrin cross talk: activation of lymphocyte function-associated antigen-1 on human T cells alters alpha4beta1- and alpha5beta1-mediated function.

A regulated order of adhesion events directs leukocytes from the vascular compartment into injured tissues in response to inflammatory stimuli. We show that on human T cells, the interaction of the beta2 integrin leucocyte function-associated antigen-1 (LFA-1) with its ligand intercellular adhesion molecule-1 (ICAM-1) will decrease adhesion mediated by alpha4beta1 and, to a lesser extent, alpha5beta1. Similar inhibition is also seen when T cells are exposed to mAb 24, which stabilizes LFA-1 in an active state after triggering integrin function through divalent cation Mg2+, PdBu, or T cell receptor/ CD3 complex (TCR/CD3) cross-linking. Such cross talk decreases alpha4beta1 integrin-mediated binding of T cells to fibronectin and vascular cell adhesion molecule-1 (VCAM-1). In contrast, ligand occupancy or prolonged activation of beta1 integrin has no effect on LFA-1 adhesion to ICAM-1. We also show that T cell migration across fibronectin, unlike adhesion, is mediated solely by alpha5beta1, and is increased when the alpha4beta1-mediated component of fibronectin adhesion is decreased either by cross talk or the use of alpha4-blocking mAb. The ability of mAb 24 Fab' fragments to induce cross talk without cross-linking LFA-1 suggests signal transduction through the active integrin. These data provide the first direct evidence for cross talk between LFA-1 and beta1 integrins on T cells. Together, these findings imply that activation of LFA-1 on the extravasating T cell will decrease the binding to VCAM-1 while enhancing the subsequent migration on fibronectin. This sequence of events provides a further level of complexity to the coordination of T cell integrins, whose sequential but overlapping roles are essential for transmigration.

Anti-Allergic Agents↗

PubMed2004

Transplantation of neuronal and glial precursors dramatically improves sensorimotor function but not cognitive function in the traumatically injured brain.

Embryonic stem (ES) cells have been investigated in various animal models of neurodegenerative disease; however, few studies have examined the ability of ES cells to improve functional outcome following traumatic brain injury (TBI). The purpose of the present study was to examine the ability of pre-differentiated murine ES cells (neuronal and glial precursors) to improve functional outcome. Rats were prepared with a unilateral controlled cortical impact injury or sham and then transplanted 7 days later with 100K ES cells (WW6G) (~30% neurons) or media. Two days following transplantation rats were tested on a battery of behavioral tests. It was found that transplantation of ES cells improved behavioral outcome by reducing the initial magnitude of the deficit on the bilateral tactile removal and locomotor placing tests. ES cells also induced almost complete recovery on the vibrissae --> forelimb placing test, whereas, media-transplanted rats failed to show recovery. Acquisition of a reference memory task in the Morris water maze was not improved by transplantation of ES cells. Histological analysis revealed a large number of surviving ES cells in the lesion cavity and showed migration of ES cells into subcortical structures. It was found that transplantation of ES cells prevented the occurrence of multiple small necrotic cavities that were seen in the cortex adjacent to the lesion cavity in media transplanted rats. Additionally, ES cells transplants also significantly reduced lesion size. Results of this study suggest that ES cells that have been pre-differentiated into neuronal precursors prior to transplantation have therapeutic potential.

Animals↗

PubMed2005

Functional outcome scales in traumatic brain injury: a comparison of the Glasgow Outcome Scale (Extended) and the Functional Status Examination.

Clinical trials aimed at developing therapies for traumatic brain injury (TBI) require outcome measures that are reliable, validated, and easily administered. The most widely used of these measures, the Glasgow Outcome Scale (GOS) and the GOS-Extended (GOS-E), have been criticized as suffering from ceiling effects. In an attempt to develop a more useful and dynamic outcome measure, the Functional Status Examination (FSE) was developed, which grades outcome across 10 functional domains. The FSE has been demonstrated to be reliable and sensitive in monitoring recovery after TBI. This manuscript compares FSE with GOS-E in a cohort of patients with a wide range of injury severities. 177 individuals who survived at least 6 months after TBI were studied. The FSE and GOS-E were administered 6-12 months after injury. FSE and GOS-E scores correlated well with each other. FSE scores were distributed throughout the range, indicating that ceiling and floor effects were not present. Physiologic measures of injury severity (Glasgow Coma Score [GCS]) did not correlate with anatomic measures (Abbreviated Injury Scale [AIS] and Injury Severity Score [ISS]). GCS correlated weakly with both outcome measures, but AIS/ISS did not. We conclude that FSE and GOS-E are reliable outcome measures for TBI survivors, and FSE may offer some advantages over GOS-E due its ability to provide a more detailed description of deficits. The majority of the variance in outcome is not accounted for by currently available measures of injury severity.

Abbreviated Injury Scale↗

PubMed2000

Dynamic renal function testing by compartmental analysis: assessment of renal functional reserve in essential hypertension.

BACKGROUND: In essential hypertension, acute haemodynamic changes due to dietary protein load cause patterns of acute changes in renal function that are fundamentally different from changes in normal controls. METHODS: Renal clearances of sinistrin, an inulin-like polyfructosan, and p-aminohippurate were determined before and after protein ingestion. These tests were performed in healthy controls and in patients with essential hypertension (mean arterial pressure of 112+/-2 mmHg, age, 52+/-2 years; mean+/-SEM) within a washout period, and after long-term treatment with carvedilol and fosinopril, respectively. RESULTS: In 15 healthy volunteers, protein ingestion increased glomerular filtration rate (GFR) from 110.3+/-3.6 to 120. 6+/-4.4 ml/min (P=0.0006; two-tailed pairwise t-test). In contrast, it led to an acute decrease in GFR in 16 hypertensive patients, from 111.8+/-2.9 to 103.6+/-3.3 ml/min (P=0.0010). The eight patients who were randomized to receive carvedilol improved in their renal response to protein (GFR increased from 101.4+/-6.4 to 107.1+/-5.4 ml/min; P=0.04), whereas the eight other patients randomized to receive fosinopril exhibited no change in GFR (final value 105+/-4.9 ml/min). In the patients, the acute shifts in renal plasma flows were not significant. Mean arterial blood pressure of the patients decreased from 112+/-2 to 100+/-3 mmHg (P=0.0015). CONCLUSIONS: In essential hypertension an acute protein load induces a decrease in GFR that may normalize under antihypertensive treatment. The acute changes in GFR can be reliably monitored by the here-described compartmental analysis method of renal functional reserve.

Adult↗