Degree Of Functional Improvement Research Articles

Comparative study of the efficacy of intra-arterial and intravenous transplantation of human induced pluripotent stem cells-derived neural progenitor cells in experimental stroke.

Cell therapy using neural progenitor cells (NPCs) is a promising approach for ischemic stroke treatment according to the results of multiple preclinical studies in animal stroke models. In the vast majority of conducted animal studies, the therapeutic efficacy of NPCs was estimated after intracerebral transplantation, while the information of the effectiveness of systemic administration is limited. Nowadays, several clinical trials aimed to estimate the safety and efficacy of NPCs transplantation in stroke patients were also conducted. In these studies, NPCs were transplanted intracerebrally in the subacute/chronic phase of stroke. The results of clinical trials confirmed the safety of the approach, however, the degree of functional improvement (the primary efficacy endpoint) was not sufficient in the majority of the studies. Therefore, more studies are needed in order to investigate the optimal transplantation parameters, especially the timing of cell transplantation after the stroke onset. This study aimed to evaluate the therapeutic effects of intra-arterial (IA) and intravenous (IV) administration of NPCs derived from induced pluripotent stem cells (iNPCs) in the acute phase of experimental stroke in rats. Induced pluripotent stem cells were chosen as the source of NPCs as this technology is perspective, has no ethical concerns and provides the access to personalized medicine. Human iNPCs were transplanted IA or IV into male Wistar rats 24 h after the middle cerebral artery occlusion stroke modeling. Therapeutic efficacy was monitored for 14 days and evaluated in comparison with the cell transplantation-free control group. Additionally, cell distribution in the brain was assessed. The obtained results show that both routes of systemic transplantation (IV and IA) significantly reduced the mortality and improved the neurological deficit of experimental animals compared to the control group. At the same time, according to the MRI data, only IA administration led to faster and prominent reduction of the stroke volume. After IA administration, iNPCs transiently trapped in the brain and were not detected on day 7 after the transplantation. In case of IV injection, transplanted cells were not visualized in the brain. The obtained data demonstrated that the systemic transplantation of human iNPCs in the acute phase of ischemic stroke can be a promising therapeutic strategy.

Molecular and cellular correlates of human nerve regeneration: ADCYAP1/PACAP enhance nerve outgrowth.

We only have a rudimentary understanding of the molecular and cellular determinants of nerve regeneration and neuropathic pain in humans. This cohort study uses the most common entrapment neuropathy (carpal tunnel syndrome) as a human model system to prospectively evaluate the cellular and molecular correlates of neural regeneration and its relationship with clinical recovery. In 60 patients undergoing carpal tunnel surgery [36 female, mean age 62.5 (standard deviation 12.2) years], we used quantitative sensory testing and nerve conduction studies to evaluate the function of large and small fibres before and 6 months after surgery. Clinical recovery was assessed with the global rating of change scale and Boston Carpal Tunnel Questionnaire. Twenty healthy participants provided normative data [14 female, mean age 58.0 (standard deviation 12.9) years]. At 6 months post-surgery, we noted significant recovery of median nerve neurophysiological parameters (P < 0.0001) and improvements in quantitative sensory testing measures of both small and large nerve fibre function (P < 0.002). Serial biopsies revealed a partial recovery of intraepidermal nerve fibre density [fibres/mm epidermis pre: 4.20 (2.83), post: 5.35 (3.34), P = 0.001], whose extent correlated with symptom improvement (r = 0.389, P = 0.001). In myelinated afferents, nodal length increased postoperatively [pre: 2.03 (0.82), post: 3.03 (1.23), P < 0.0001] suggesting that this is an adaptive phenomenon. Transcriptional profiling of the skin revealed 31 differentially expressed genes following decompression, with ADCYAP1 (encoding pituitary adenylate cyclase activating peptide, PACAP) being the most strongly upregulated (log2 fold-change 1.87, P = 0.0001) and its expression was associated with recovery of intraepidermal nerve fibres. We found that human induced pluripotent stem cell-derived sensory neurons expressed the receptor for PACAP and that this peptide could significantly enhance axon outgrowth in a dose-dependent manner in vitro [neurite length PACAP 1065.0 µm (285.5), vehicle 570.9 μm (181.8), P = 0.003]. In conclusion, carpal tunnel release is associated with significant cutaneous reinnervation, which correlates with the degree of functional improvement and is associated with a transcriptional programme relating to morphogenesis and inflammatory processes. The most highly dysregulated gene ADCYAP1 (encoding PACAP) was associated with reinnervation and, given that this peptide signals through G-protein coupled receptors, this signalling pathway provides an interesting therapeutic target for human sensory nerve regeneration.

Nutritional Status According to the Mini Nutritional Assessment Predicts Speed and Degree of Functional Improvement and Discharge Outcomes in Rehabilitation Patients

This retrospective observational study evaluated the association between nutritional status, functional ability and discharge outcomes. Data from 1430 older rehabilitation patients (43% male, median age 79 years, interquartile range: 74–84) were analyzed. One fifth (20.6%, n = 294) of patients were malnourished on admission to rehabilitation. Three important findings were evident. Firstly, nutritional status on admission to rehabilitation was associated with reduced functional, motor, cognitive and feeding scores on admission and discharge (all P < 0.05). Secondly, malnutrition at admission was associated with significantly slower gains in rehabilitation. Finally, malnutrition at admission was associated with significantly higher odds of a decline in functional ability during admission (OR 3.95; 95% CI: 2.14–7.27), and almost three times greater odds of additional care requirements on discharge (OR: 2.9 ((95% CI: 1.02–8.3). The nutritional status of patients on admission to inpatient rehabilitation is a predictor of both the speed and degree of rehabilitation gains and discharge outcomes.

The role and outcome of cardiac rehabilitation program in patients with atrial fibrillation.

Atrial fibrillation (AF) is associated with diminished cardiac function, and exercise tolerance. We sought to investigate the role of cardiac rehabilitation program (CR) in patients with AF. The study included 2165 consecutive patients that participated in our CR program between the years 2009 to 2015. All were evaluated by a standard exercise stress test (EST) at baseline, and upon completion of at least 3 months of training. Participants were dichotomized according to baseline fitness and the degree of functional improvement. The combined primary end point was cardiac related hospitalization or all-cause mortality. A total of 292 patients had history of AF, with a mean age of 68 ± 9 years old, 76% of which were males. The median predicted baseline fitness of AF patients was significantly lower compared to non-AF patients (103% vs 122%, P < 0.001, respectively). Prominent improvement was achieved in the majority of the patients in both groups (64% among AF patients and 63% among those without AF). Median improvement in fitness between stress tests was significantly higher in patients with AF (124% vs 110%, P < 0.001, respectively). Among AF patients, high baseline fitness was associated with a lower event rates (HR 0.40; 95%CI 0.23-0.70; P = 0.001). Moreover, prominent improvement during CR showed a protective effect (HR 0.83; 95% CI 0.69-0.99; P = 0.04). In patients with AF participating in CR program, low fitness levels at baseline EST are associated with increased risk of total mortality or cardiovascular hospitalization during long-term follow-up. Improvement on follow-up EST diminishes the risk.

The prognostic significance of improvement in exercise capacity in heart failure patients who participate in cardiac rehabilitation programme.

Introduction There are limited contemporary data regarding the association between improvement in cardiovascular fitness in heart failure patients who participate in a cardiac rehabilitation programme and the risk of subsequent hospitalisations. Methods The study population comprised 421 patients with heart failure who participated in our cardiac rehabilitation programme between the years 2009 and 2016. All were evaluated by a standard exercise stress test before initiation, and underwent a second exercise stress test on completion of 3 ± 1 months of training. Participants were dichotomised by fitness level at baseline, according to the percentage of predicted age and sex norms achieved. Each group was further divided according to its degree of functional improvement, between the baseline and the follow-up exercise stress test. Major improvement was defined as improvement above the median value in each group. The combined primary endpoint was cardiac hospitalisation or all-cause mortality. Results A total of 211 (50%) patients had low baseline fitness (<73% (median)) for age and sex-predicted metabolic equivalents of task value. Compared to patients with higher fitness, those with a low baseline fitness were more commonly smokers, had diabetes and were obese ( P < 0.05 for all). Multivariable Cox proportional hazard regression analysis showed that, independent of baseline capacity, an improvement of 5% of predicted fitness was associated with a corresponding 10% reduced risk of cardiac hospitalisation or all-cause mortality ( P < 0.001). Conclusion In heart failure patients participating in a cardiac rehabilitation programme, improved cardiovascular fitness is associated with reduced mortality or cardiac hospitalisation risk during long-term follow-up, independent of baseline fitness.

Clinical features and inpatient rehabilitation outcomes of infection-related myelopathy.

This was a retrospective cohort study. The objectives of this study were to determine clinical features of infection-related myelopathy (IRM) and functional outcomes compared with other nontraumatic and traumatic myelopathies. US academic inpatient rehabilitation unit. This was a 16-year retrospective review of patients with myelopathy discharged from inpatient rehabilitation between 1 January 1995 and 31 December 2010. Patients comprised three injury groups: IRM, nontraumatic myelopathy (NTM) and traumatic spinal cord injury (TSCI). Information collected includes demographic characteristics, functional data, length of stay, injury completeness and discharge destination. Primary outcome measures were change in Functional Independence Measure (FIM) and daily FIM change. For IRM, data were collected regarding injury characteristics, risk factors, presenting symptoms, neurologic impairment level and treatment. Of the 1601 patients, 40 (2.5%) had IRM, 1105 (69.0%) had NTM and 456 (28.5%) had TSCI. IRM mean (s.d.) age was 58.6 (15.7) years (male gender, 72.5%). The majority in each group had incomplete injuries. IRM had longer lengths of stay (P<0.001), lower admission (P=0.001) and discharge (P=0.005) FIM scores and lower FIM daily change (P=0.002) than NTM. Degree of functional improvement was similar in all groups, and most patients in each group were discharged home. Infectious pathogens were bacterial (80.0%, n=32), viral (7.5%, n=3), tuberculous (7.5%, n=3), parasitic (2.5%, n=1) and multiple types (2.5%, n=1). The most common bacterial cause (65.6%) was Staphylococcus aureus. Infectious etiologies comprise a small proportion of NTM but represent a unique entity with distinct recovery patterns and outcomes. These patients can achieve similar functional improvements as other NTM patients during inpatient rehabilitation, although over a longer period of time.

Selective inhibition of ASIC1a confers functional and morphological neuroprotection following traumatic spinal cord injury

Tissue loss after spinal trauma is biphasic, with initial mechanical/haemorrhagic damage at the time of impact being followed by gradual secondary expansion into adjacent, previously unaffected tissue. Limiting the extent of this secondary expansion of tissue damage has the potential to preserve greater residual spinal cord function in patients. The acute tissue hypoxia resulting from spinal cord injury (SCI) activates acid-sensing ion channel 1a (ASIC1a). We surmised that antagonism of this channel should provide neuroprotection and functional preservation after SCI. We show that systemic administration of the spider-venom peptide PcTx1, a selective inhibitor of ASIC1a, improves locomotor function in adult Sprague Dawley rats after thoracic SCI. The degree of functional improvement correlated with the degree of tissue preservation in descending white matter tracts involved in hind limb locomotor function. Transcriptomic analysis suggests that PcTx1-induced preservation of spinal cord tissue does not result from a reduction in apoptosis, with no evidence of down-regulation of key genes involved in either the intrinsic or extrinsic apoptotic pathways. We also demonstrate that trauma-induced disruption of blood-spinal cord barrier function persists for at least 4 days post-injury for compounds up to 10 kDa in size, whereas barrier function is restored for larger molecules within a few hours. This temporary loss of barrier function provides a " treatment window" through which systemically administered drugs have unrestricted access to spinal tissue in and around the sites of trauma. Taken together, our data provide evidence to support the use of ASIC1a inhibitors as a therapeutic treatment for SCI. This study also emphasizes the importance of objectively grading the functional severity of initial injuries (even when using standardized impacts) and we describe a simple scoring system based on hind limb function that could be adopted in future studies.

Clinical utility of chosen factors in predicting post-stroke depression: a one year follow-up.

The aim of the study was to identify possible interrelation between the presence of post-stroke depression (PSD) and chosen clinical and demographic parameters. Initially 116 patients (61.4 ± 12.6 years, women N = 42) hospitalized in Neurology Department, Medical University of Gdańsk (April 2003 - December 2005) due to first ischemic stroke, were included in the study. We analysed demographic data, the lesion's side and location according to neuroimaging and global neurological deficit estimated on the first day after the stroke and at discharge using NIHSS (National Institutes of Health Stroke Scale) and Barthel Index of Activity of Daily Living. Psychiatric evaluation was done:6 (42 ± 3 days) and 12 weeks (84 ± 7 days), as well as 6 (±14 days) and 12 months (±14 days) after stroke based on ICD-10 and functional assessment scale (Rankin Scale). Depression was diagnosed in 29 patients (27.6%). No correlation was found between PSD and sex or age. On the first day and at discharge patients without PSD were functioning slightly better but the difference was not statistically significant. We found association between the presence of PSD and the results of Rankin scale with the exception of degree of improvement during whole observation. In the group of patients with PSD left hemisphere strokes were slightly more common, but the difference did not reach statistical significance. The location of lesions in frontal lobes and basal ganglia was associated with presence of depression. We found the association between the presence of PSD and location of lesions (frontal lobes or basal ganglia), as well as with the degree of functional improvement during 12 months after stroke.

Optimizing immunoglobulin G therapy in chronic autoimmune neuropathies.

Prolonged intravenous immunoglobulin (IVIg) therapy is frequently used for the treatment of chronic autoimmune neuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN). Recent studies of the electrophysiology and immunology of various neurological diseases, including CIDP, suggest that antibody-induced reversible dysfunction of nodes of Ranvier plays an important role in conduction block and morbidity 1. This may be more important, at least in the short term, than demyelination or axon destruction. The IVIg doses and dosing intervals are usually chosen empirically due to a paucity of data from dose-response and pharmacodynamic studies. The use of 2 g/kg as loading dose and maintenance doses of 1 g/kg every 3–4 weeks are common. European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) guidelines suggest that the dose and frequency of IVIg should be tailored to an individual patient's needs 2. However, there are no recommendations as to how this can be achieved or the outcomes upon which adjustments in therapy should be based. Clinical observations suggest that with currently used immunoglobulin (Ig) regimens the beneficial effects of each dose of IVIg may be transient, wearing off before the next cycle of treatment is required. These observations have been confirmed by case reports. A patient with CIDP repeatedly showed improvement in ankle dorsiflexion over the first 5–9 days following the administration of IVIg. The improvement was sustained for approximately 10 days but then declined, reaching pretreatment levels by the end of the month 3. These periodic fluctuations in strength were also reported in a patient with MMN on monthly IVIg therapy 4. However, this patient was switched to subcutaneous immunoglobulin (SCIg) therapy and, with a 25% increase in total monthly dose, his disease stabilized. Weekly SCIg has been investigated as a means of continuously maintaining high serum IgG levels, resulting in stabilization of neuromuscular function in CIDP and MMN patients 5–8. Significant variations in IgG metabolism have been reported among patients with CIDP 9. These differences were unrelated to the administered dose, weight, body mass index or degree of functional improvement. However, the patient-specific post-infusion rise in IgG levels, which may be dependent upon the individual rate of IgG metabolism, may explain the interpatient differences in infusion frequency requirements. The optimum dosage and frequency of IVIg infusions appears to be patient-specific 9. It has been shown that actual doses and dosing intervals vary from conventional empirical dosing, suggesting that physicians may already be adjusting doses based on the individual patient's clinical condition and treatment response 10. A prospective study has shown that CIDP patients maintain strength optimally when their IgG levels reach a plateau supported by infusions as frequent as once every 10 days. The intra- and interpatient variability in IgG may indicate that individualized constant levels of IgG facilitate achieving clinical stability 11. Overall, these studies show that many patients with CIDP have increased benefit when IVIg is administered at more frequent intervals, with 30–60% of patients showing improvement when IVIg is administered at intervals of 10–14 days or less 9–11. An ongoing study supported by CSL Behring in collaboration with AxelaCare has demonstrated that grip strength and disability measurements performed frequently by the patient at home can be reported wirelessly, collected by a database service, and reported to the physician 12. This information can prove useful for assessing the extent and duration of responses to individual IgG doses. In addition, this type of frequent data collection can be used to identify patients who would benefit from weekly SCIg rather than IVIg every 3−4 weeks and those in whom IgG therapy is ineffective. Currently, Ig replacement therapy is widely used in the treatment of chronic autoimmune neuropathies. Individualization of IgG treatment regimens may optimize efficacy and minimize disability. Further studies are needed to determine whether patient-specific regimens result in improved long-term outcomes.

8. Evolution and recovery of motor function post-stroke

Background and Objectives With the advent of novel neuromodulatory interventions in post-stroke recovery, the evolution of intracortical excitability changes, particularly those over the contralesional hemisphere following stroke, and their relevance to functional recovery requires further clarification. As such, the present study utilized a prospective longitudinal design over an 18-month period from stroke onset, to investigate the evolution of intracortical excitability over both motor cortices and their relation to functional recovery. Methods A total of thirty-three acute stroke patients and 29 control subjects were recruited in the study. Paired-pulse transcranial magnetic stimulation and comprehensive clinical assessments were undertaken at stroke onset and then repeated at 3-, 6-, 12-, and 18-months follow-up. Results Immediately after stroke, short-interval intracortical inhibition (SICI) was significantly reduced in both hemispheres compared with controls that correlated with the degree of functional improvement over the first 3-months. Over the follow-up period, ipsilesional SICI remained reduced in all patient groups, whilst SICI over the contralesional hemisphere remained suppressed only in the groups with cortical stroke and more severe baseline functional impairment. Furthermore, contralesional SICI was more reduced in these groups of patients compared to those with subcortical stroke location and milder baseline impairment during the longitudinal assessment period. Clinical scores demonstrated improvement over this period with the most significant changes occurring in the first 3-months. Conclusion Intracortical disinhibition occurs in both hemispheres immediately following acute stroke that likely represent functionally relevant changes supporting the recovery process in stroke. Whilst changes in the lesioned hemisphere persisted over the period of recovery in all patients, contralesional intracortical hyperexcitability persisted in patients with cortical strokes and those with more severe baseline functional impairment, suggesting that ongoing contralesional network recruitment may be necessary for those patients who have significant disruptions to the integrity of ipsilesional motor pathways. The study has demonstrated that evolution of cortical excitability, particularly over the contralesional hemisphere, may vary between patients with differing baseline stroke and clinical characteristics, and thereby has important implications towards the development of protocols for neuromodulatory brain stimulation in stroke recovery.

Size matching in lung transplantation: An evidence-based review

The evidence base for size matching between donors and recipients in lung transplantation has not recently been reviewed in a comprehensive manner. Our aim in this study was to assimilate published studies that have addressed size matching of donors to recipients and to establish a pragmatic understanding of the range of lung sizes that may be used for lung transplantation. A comprehensive literature search was performed using Medline and PubMed up to and including September 2012, to identify scientific articles that relate to size matching between donors and lung transplant recipients. Seventy-two articles were identified, of which 21 had addressed the question of the impact of size mismatching on outcomes in lung transplantation. No study has specifically tested the consequences of intentionally mismatching above or below the hypothetical limits for double lung transplantation of a predicted total lung capacity for the donor of between 75% and 125% of the recipient predicted total lung capacity as set out in the ISHLT consensus report on lung donor acceptability criteria. Research is lacking that has robustly defined limits for size mismatch for single lung transplantation and for recipients with restrictive lung pathologies such as pulmonary fibrosis. Published research on the impact of size mismatching between lung transplant donors and recipients is limited by study design and size. It is centered on addressing the issue of mismatch in double lung transplantation in cohorts with a diagnostically heterogeneous make-up and in single lung transplant patients with chronic obstructive pulmonary disease.

Immunoglobulin G level variations in treated chronic inflammatory demyelinating polyneuropathy: clues for future treatment regimens?

Intravenous immunoglobulins (IVIg) are effective for treating chronic inflammatory demyelinating polyneuropathy (CIDP), although treatment needs are variable and need to be individualized. Dose and frequency requirements are not currently predictable in advance. In Guillain-Barré syndrome, IVIg interpatient pharmacokinetic variations have been demonstrated in relation to clinical outcome. We studied 15 patients with CIDP following two routine courses of IVIg. IgG levels were assessed pretreatment and 14 days post-treatment. Best clinical response (BCR) was ascertained in each case, predefined, according to individual patients' circumstances, on the 10 m walk, or MRC sum score, or Jamar grip dynamometry. Correlations between IgG level variations, doses administered, weight, body mass index, BCR and infusion interval were determined. Postinfusion rise in IgG levels were correlated in individual patients (p = 0.005), but interpatient variability was high. No correlations were ascertained between IgG level variation and weight, body mass index, BCR, total dose of IVIg administered, or dose of IVIg administered per kilogram per week. There were significant correlations between total dose administered and post-infusion IgG level at 14 days (p = 0.004) and between infusion interval and mean rise in IgG level (p = 0.001) These findings suggest significant variability in IgG metabolism between patients, unrelated to minimal effective dose administered, weight, body mass index or degree of functional improvement. Required frequency of IVIg infusions may, however, importantly relate to patient-specific post-infusion rise in IgG levels hence possibly explaining inter-patient differences in treatment frequency needs. IgG level monitoring may be helpful in establishing optimum treatment regimens in individual cases.

Functional improvement and neuroplastic effects of anodal transcranial direct current stimulation (tDCS) delivered 1 day vs. 1 week after cerebral ischemia in rats

Transcranial direct current stimulation (tDCS) is an emerging tool for improving recovery from stroke. However, there has been no trial to determine whether it has a therapeutic benefit in the early stage of cerebral ischemia, and there is no consensus on the optimal time window of stimulation. Here, we described the effects of anodal tDCS in early cerebral ischemia, assessing functional improvements and changes in neuronal plasticity, and identifying the optimal time window for delivering tDCS to maximize functional gains. Thirty rats were randomly assigned to three groups: sham (n=10); early tDCS (ET), receiving tDCS 1day after ischemia for 5days (n=10), and late tDCS (LT), receiving tDCS 1week after ischemia for 5days (n=10). Both ET and LT groups showed improved Barnes maze performance and motor behavioral index scores. However, only the LT group exhibited improvement in beam balance test. Immunohistochemical stainings showed that the ET group reinforced notable MAP-2 expression and the LT group enhanced mainly the level of GAP-43 in both peri-lesional and contralesional cortex. These immunohistochemical results had significant correlation with behavioral and cognitive functions. However, brain MRI and 1H MRS showed no significant differences among the three groups in ischemic volume and metabolic alteration. These results suggest that anodal tDCS has the potential to modulate neural plasticity around the ischemic penumbra and even in the contralesional area without aggravating infarction volume and metabolic alteration. The degree of functional improvement was slightly greater when tDCS was applied 1week rather than 1day after ischemic injury.

Implant Survival, Knee Function, and Pain Relief After TKA: Are There Differences Between Men and Women?

As efforts continue to improve the results of TKA, the potential influence of sex and gender on long-term survival of implants, knee function, pain relief, and patient satisfaction remains relevant, particularly given the increased incidence of osteoarthritis of the knee in women and reports that women derive equal benefit from TKA. This article reviews the literature pertinent to the question of whether long-term survival, knee function, pain relief, and patient satisfaction after TKA differ between men and women. Large clinical series (> 1000 patients) published in the last 10 years were identified in PubMed and reviewed. Men may be at higher risk of revision surgery than women. Sex/gender has been consistently shown to impact both function and pain relief both before and after TKA. Although women achieve at least the same degree of functional improvement as men, women have worse preoperative physical function and do not reach the same final level of physical function as men. Likewise women may have similar or even greater improvement in pain after arthroplasty than men but still have final pain scores that are less favorable. Further research is required to understand the sex and gender differences contributing to implant survival, physical function, and pain relief after TKA. Strategies need to be developed to identify any patient who is at higher risk of implant failure, suboptimal postoperative function, and incomplete pain relief.

Wrist Arthrodesis With Volar Plate Fixation in Cerebral Palsy

Wrist arthrodesis can obtain better appearance, hygiene, and ease of daily care, with some degree of functional improvement in patients with cerebral palsy with a severe wrist flexion deformity. Rigid fixation using a dorsal plate and screws has been accepted as a reliable technique, although hardware-related problems are relatively common. We describe a volar plate fixation technique for wrist arthodesis in cerebral palsy, which can allow concomitant flexor tendon release and avoid a prominent hardware and a cosmetically undesirable scar on the dorsum of the wrist.

Erythropoietin induces neuroprotection in experimental intracerebral hemorrhage via eNOS upregulation and STAT3 activation

Erythropoietin (EPO) is tissue-protective in preclinical models of ischemic, traumatic, toxic, and inflammatory injuries. Both EPO and its receptor are expressed throughout the brain in glial cells, neurons and endothelial cells. In this study, we investigated whether EPO treatment reduces cerebral inflammation, edema and perihematomal cell death after experimental intracerebral hemorrhage (ICH), and whether functional recovery is enhanced. ICH was induced using stereotaxic infusion of collagenase into the left basal ganglia of adult rats. EPO (5,000 IU/kg) or PBS was administered intraperitoneally at 20 minutes after ICH induction and daily afterwards for 3 or 14 days. Seventy-two hours after ICH induction, we checked hematoma volume using spectrometric methods and water content in both hemispheres separately. TUNEL, activated caspase-3 staining and caspase-3 activity assay were done for the perihematomal cell death, and myeloperoxidase (MPO) activity was analyzed for inflammation. Expression of eNOS, pSTAT3, STAT3, and pSTAT5 was measured by western blotting. Behavioral tests were performed weekly up to 35 days after ICH. The volume of hemorrhage was decreased in EPO-treated group by 25% at 3 days after ICH (p<0.05). EPO reduced the brain water content in the lesioned hemisphere compared with ICH-only group (p<0.01). In EPO-treated group, the numbers of TUNEL+, MPO+, and OX42+ cells, activated caspase-3+ cells were decreased in the periphery of hematoma (p<0.01). Western blotting showed significant upregulation of eNOS and pSTAT3 expression in EPO-treated group compared with the ICH-only group, while protein expression of STAT3, STAT5 and pSTAT5 has not been changed. EPO-treated rats recovered better at 14 days after ICH throughout 35 days in both rotarod and limb placing tests (p<0.01), and the degree of functional improvement in EPO-treatment group was faster and better than that of ICH-only group. In this study, we provide evidences that EPO has therapeutic effects in ICH. EPO treatment enhances the functional recovery, and induces the pleiotropic neuroprotection including the reduction of hematoma volume and edema, and the inhibition of apoptosis and neuroinflammation. Both eNOS upregulation and enhanced STAT3 phosphorylation may be involved in this action of EPO.

The role of minimal surgery with renal preservation in abnormal complete duplex systems.

Among 36 children, mostly less than 1 year of age, referred for a complete duplex-system anomaly, 18 were diagnosed before birth by obstetrical ultrasonography where a diagnosis of dilated upper urinary tract was the most frequent report; in the remaining cases urinary tract infection was the main presenting symptom. Five children had bilateral anomalies. Principal diagnoses associated with the complete duplex system were: 18 ureteroceles (UC) (11 extravesical [EUC] with bladder-neck or urethral extension, 7 intravesical [IUC]), 5 ectopic ureters without UC and 28 lower-polar vesicoureteral reflux (VUR) associated in 6 with upper polar VUR. The initial assessment was based on a voiding cystogram and radionuclide scan. Renal-polar function was severely impaired when major ureteral ectopia or severe primary reflux was present. Primary surgery was performed in 8 patients, demolitive in 4 (3 upper-polar nephrectomies, 1 nephrectomy) and reconstructive in 4 (duplex en-bloc reimplantation); staged management with minimal endoscopic incision was undertaken in 15 UCs (9 EUCs and 6 IUCs). Expectant management was elected in all cases of mild primary, single, or double VUR not associated with UC and was followed by spontaneous reduction in one-half of the cases. Secondary VUR complicated endoscopic incision in 2 of 6 IUCs and 5 of 9 EUCs; a certain degree of functional improvement after decompression could be observed in all IUCs versus only 2 EUCs. Twenty-one patients requested secondary surgery; 17 needed an open intravesical procedure for ureteral reimplantation, combined in 8 with UC excision and bladder-floor reconstruction and in 5 with upper-pole nephrectomy. A nephrectomy was required in 4 cases. All primary or secondary demolitive procedures involved 9 of 11 EUCs extravesical and 2 of 5 ectopic ureters. EUCs and ureteral ectopia were associated with severe renal-polar damage, and function was rarely affected by primary decompressive procedures even in prenatally detected, uninfected cases. Endoscopic incision of EUCs was frequently followed by secondary VUR, which made secondary intravesical operations more complex. For these reasons, primary elective resection of a dysplastic upper pole is preferable in most cases to temporary decompressive measures. Conservative surgery is always indicated in IUC, which may benefit from endoscopic decompression. Isolated VUR involving the lower pole of a completely duplicated system may respond to expectant management in a significant number of cases.

Relationship between donor/recipient lung size mismatch and functional outcome in single lung transplantation for COPD.

Single lung transplantation is an effective treatment for patients with severe chronic obstructive pulmonary disease. Pulmonary hyperinflation, which is seen in most patients with severe chronic obstructive pulmonary disease, makes the task of appropriately matching the donor and recipient difficult. It seems that the optimal matching strategy remains undefined. No correlation between donor/recipient size match (actual and predicted) and the degree of functional improvement after single lung transplantation was found. There were no significant differences noted when comparing the functional outcomes of right and left lung transplant recipients. It was concluded that the chronic hyperinflation associated with severe chronic obstructive pulmonary disease allows for the use of significantly larger donors. The use of expanded donor/recipient size match criteria in patients with severe chronic obstructive pulmonary disease may shorten the waiting period prior to single lung transplantation and provide better utilization of donor organs.

Relationship between Donor/Recipient Lung Size Mismatch and Functional Outcome in Single Lung Transplantation for COPD

Single lung transplantation is an effective treatment for patients with severe chronic obstructive pulmonary disease. Pulmonary hyperinflation, which is seen in most patients with severe chronic obstructive pulmonary disease, makes the task of appropriately matching the donor and recipient difficult. It seems that the optimal matching strategy remains undefined. No correlation between donor/recipient size match (actual and predicted) and the degree of functional improvement after single lung transplantation was found. There were no significant differences noted when comparing the functional outcomes of right and left lung transplant recipients. It was concluded that the chronic hyperinflation associated with severe chronic obstructive pulmonary disease allows for the use of significantly larger donors. The use of expanded donor/recipient size match criteria in patients with severe chronic obstructive pulmonary disease may shorten the waiting period prior to single lung transplantation and provide better utilization of donor organs.

Value of exercise testing for prediction of physical and psychosocial rehabilitation potential 3 months after acute myocardial infarction.

In 147 patients exercise tests were performed at the beginning and after 1 year of an ambulatory rehabilitation program. Measurements of both tests and the degree of functional improvement were correlated with patients' characteristics, the results of a psychological analysis using the Freiburger Personality Inventory and a patient's questionnaire for self-assessment. Among the major determinants for functional improvement were age, location of the infarct, rate of participation and greater initial functional impairment. High degree of psychosomatic impairment accompanied low levels of exercise capacity, the patients' self-assessment showed no correlation with exercise performance.