Tenascin-C expression by neurons and glial cells in the rat spinal cord: Changes during postnatal development and after dorsal root or sciatic nerve injury

Summary We have usedin situ hybridization with a digoxigenin-labelled probe for tenascin-C mRNA and immunocytochemistry with antibodies against tenascin-C, glial fibrillary acidic protein, OX-42 and the 200 kDa neurofilament protein to study the expression, distribution and cellular relationships of tenascin-C mRNA and protein in the developing (postnatal) and adult spinal cord of rat, and the effects thereon of dorsal root, ventral root and sciatic nerve injuries. The most interesting finding was that on postnatal day 7 (P7), P14 and in the adult, but not on P0 or P3, a group of neurons in the lumbar ventral horn expressed the tenascin-C mRNA gene. They represented about 5% of ventral horn neurons in the adult and were among the smaller such neurons. Since 40–60% of such cells were lost at P13 following sciatic nerve crush on P0, some were almost certainly motor neurons. In addition, we found that at P0 and P3, mRNA-containing glial cells were widespread in grey and white matter but sparse in the developing dorsal columns; tenascin-C immunofluorescence showed a similar distribution. By P7 there were fewer mRNA-containing cells in the ventral horns and in the area of the dorsal columns containing the developing corticospinal tract where immunofluorescence was also weak. At P14 there were no glial-like mRNA-containing cells in the grey matter; such cells were confined to the periphery of the lateral and ventral white columns but were present throughout the dorsal columns where tenascin-C immunofluorescence was also strong. No glial-like mRNA-containing cells were present in the adult lumbar spinal cord and tenascin-C immunofluorescence was confined to irregular patches in the ventral horn, especially around immunonegative cell bodies of small neurons, a zone around the central canal, and a thin zone adjacent to the glia limitans. Thus the expression of tenascin-C is differentially developmentally regulated in the grey matter and in different parts of the white matter. Three days after injury of dorsal roots L4–6, many cells containing tenascin-C mRNA, some identified as glial fibrillary acidic protein-positive astrocytes, were present in the ipsilateral dorsal column, but were rare after longer survivals. Immunoreactivity, however, was elevated in the ipsilateral dorsal column at 3 days, remained high for several months and disappeared at 6.5 months. Dorsal root injury had no effect on tenascin-C mRNA or protein in the grey matter. Sciatic nerve or ventral root injury had no effect on these molecules in any part of the spinal cord.     

Advanced Parkinson's disease: use of partial dopamine agonist, ciladopa

Ciladopa is a partial dopamine agonist that is effective in patients with advanced Parkinson's disease who are no longer satisfactorily responding to levodopa. Thirty-one patients participated in a double-blind randomized study of ciladopa (added to levodopa) versus placebo. Among 21 patients randomized to treatment with ciladopa and levodopa, there was a 32% decrease in symptoms on the Modified Columbia University Disability Scale. This change was significant, p less than or equal to 0.05. Eight of the 21 patients (38%) improved by at least 50%. The mean number of hours "on" increased by 20%. This change was significant, p less than or equal to 0.05. Five of the 21 patients (24%) were on for at least 4 hours more than at baseline. Dyskinesias were not increased. The mean dose of ciladopa was 19.5 mg/d. The mean dose of levodopa in Sinemet was decreased by 10%. Studies with ciladopa in humans had to be discontinued because of the occurrence of microscopic testicular tumors in some rodents. Although improvement in patients taking ciladopa was modest, there were few adverse effects. These results are encouraging, because two other partial agonists are now available, and they may be as effective as ciladopa.     

Histology, immunohistochemistry, and ultrastructure of the verruga in Carrion's disease

Twenty-six verruga peruana nodules were studied. The presence of Factor VIII-related antigen and Ulex europaeus lectin binding, and the ultrastructural finding of rudimentary cell junctions and pinocytotic vesicles establish the endothelial character of the proliferating cells in the verruga nodules. Whereas superficial lesions could show an angiomatoid pattern, deep-situated nodules tended to present a compact type of growth. Electron-microscopic studies have shown that Bartonella bacilliformis was found abundantly in the extracellular spaces in the florid lesions and that no organisms were present in the late, resolving subcutaneous nodules. Although no true intracellular "viable" microorganisms were noted, pseudopods of cytoplasm entrapping one or two bacteria and surrounding matrix substance were seen often. The characteristics of cytoplasmic inclusions previously described in verruga cells as "chlamydozoa" were detailed. The ultrastructure of the inclusions corresponded to endothelial phagocytic cells in which complex invaginations of the cell surface had produced a labyrinth of interconnected channels and vacuoles containing degraded bacteria, extracellular matrix components, or both. We conclude that in light microscopy the finding of Rocha-Lima's inclusions is the only definite morphologic evidence of the presence of bartonella in verruga lesions.     

Combined use of benserazide and carbidopa in Parkinson's disease

The pharmacokinetics of levodopa differs when it is combined with benserazide or carbidopa. Peak dopa levels are higher, occur sooner, but decline more rapidly with benserazide. Although many patients respond better to one drug than the other, we sought to exploit the differences in pharmacokinetics by giving both drugs to the same patient. Benserazide was combined with carbidopa in 38 patients who were experiencing a diminished response to carbidopa, including 22 patients with diurnal oscillations in performance, "wearing off" or on-off phenomena. Previous attempts to change the dose, sequence, or ratio of levodopa to carbidopa in these patients had been unrewarding. Ten of the patients improved on the combination of benserazide and carbidopa, with a 30% decline in disability. The mean dose of levodopa:carbidopa before benserazide was 910:100 (9 to 1 ratio); the mean dose of levodopa:benserazide was 355:90 (4 to 1 ratio). The mean dose of levodopa:carbidopa + benserazide was 925:155 (6 to 1 ratio). The combination of carbidopa with benserazide is useful in some parkinsonian patients.     

Longitudinal Changes in Muscle Mass,Muscle Strength,and Physical Performance in Acutely Hospitalized Older Adults

ObjectivesAcute hospitalization may lead to a decrease in muscle measures, but limited studies are reporting on the changes after discharge. The aim of this study was to determine longitudinal changes in muscle mass, muscle strength, and physical performance in acutely hospitalized older adults from admission up to 3 months post-discharge.DesignA prospective observational cohort study was conducted.Setting and ParticipantsThis study included 401 participants aged ≥70 years who were acutely hospitalized in 6 hospitals. All variables were assessed at hospital admission, discharge, and 1 and 3 months post-discharge.MethodsMuscle mass in kilograms was assessed by multifrequency Bio-electrical Impedance Analysis (MF-BIA) (Bodystat; Quadscan 4000) and muscle strength by handgrip strength (JAMAR). Chair stand and gait speed test were assessed as part of the Short Physical Performance Battery (SPPB). Norm values were based on the consensus statement of the European Working Group on Sarcopenia in Older People.ResultsA total of 343 acute hospitalized older adults were included in the analyses with a mean (SD) age of 79.3 (6.6) years, 49.3% were women. From admission up to 3 months post-discharge, muscle mass (?0.1 kg/m²; P = .03) decreased significantly and muscle strength (?0.5 kg; P = .08) decreased nonsignificantly. The chair stand (+0.7 points; P < .001) and gait speed test (+0.9 points; P < .001) improved significantly up to 3 months post-discharge. At 3 months post-discharge, 80%, 18%, and 43% of the older adults scored below the cutoff points for muscle mass, muscle strength, and physical performance, respectively.Conclusions and ImplicationsPhysical performance improved during and after acute hospitalization, although muscle mass decreased, and muscle strength did not change. At 3 months post-discharge, muscle mass, muscle strength, and physical performance did not reach normative levels on a population level. Further research is needed to examine the role of exercise interventions for improving muscle measures and physical performance after hospitalization.     

Redox potential in human semen: Validation and qualification of the MiOXsys assay

Seminal oxidative stress (OS) is a major contributing factor to male infertility. Semen analysis cannot identify reactive oxygen species (ROS), which can be measured using a chemiluminescence assay. Measurement of redox potential provides a more comprehensive assessment of OS, although the test has yet to be fully validated. This study aimed to validate the MiOX^sys analyser for measuring static oxidation–reduction potential (sORP). Results demonstrated that duplicate measurements must be taken, sensors must be batch tested, and sockets should be regularly changed to avoid inconsistency in measurement. Measurement of sORP using MiOX^sys exhibited good reproducibility across different operators (p = 0.469), analysers (p = 0.963) and days (p = 0.942). It is not affected by mechanical agitation (p = 0.522) or snap freezing and thawing (p = 0.823). The stability of sORP over time requires further verification, particularly in samples with high initial sORP. Measurement is temperature sensitive between 2 and 37°C, significantly increasing with increasing temperature (p = 0.0004). MiOX^sys is a more stable assay for assessing OS than chemiluminescence methods and permits greater flexibility for sample handling. MiOX^sys could be implemented to complement semen analysis as part of routine diagnostic testing for male infertility and may be useful in identifying contributing factors to idiopathic infertility.     

Meditative and mind-body practice among patients with genitourinary malignancy

Introduction and objectiveResearch on the utility of meditative and mind-body (MB) practices has increased dramatically in the last two decades and both have been suggested as useful adjuncts in coping with stressors associated with cancer survivorship. There exists little data on use among genitourinary (GU) cancer survivors. This study seeks to describe meditative and MB utilization among GU cancer survivors.MethodsAnalysis of data from the 2012 and 2017 National Health Interview Survey was conducted. Patients aged 40 and older reporting a history of any cancer diagnosis (including 3 GU cancers) were included in the analysis. We explored questions about meditative and MB practices in the past 12 months. Complex Samples Logistic regression was performed to compare the relationship between cancer status and use of these practices.ResultsSelf-reported meditative practices were more prevalent in 2017 (17%) than in 2012 (5%). Patients who self-reported a cancer diagnosis of any kind were significantly more likely to utilize meditative practices. Patients with kidney cancer were significantly more likely to meditate and trended towards higher MB utilization. In contrast, bladder cancer patients were less likely to meditate and use MB practices. Increases in meditation were greater than those seen for MB in all groups.ConclusionsMeditative and MB practices increased in prevalence between 2012 and 2017 with notable heterogeneity between cancer types. Given the potential benefit, more broad incorporation into survivorship programs may be warranted. Future work should explore the significance of this heterogeneity and the utility of these practices to patients with urologic malignancy.     

Representative dynamic ranges of spinal alignment during gait in patients with mild and severe adult spinal deformities

BACKGROUND CONTEXTSurgical correction strategies for adult spinal deformity (ASD) relies heavily on radiographic alignment goals, however, there is often debate regarding degree of correction and how static alignment translates to physical ability in daily life. Kinematic analysis has the potential to improve the concept of ideal spinal alignment by providing clinically meaningful estimates of dynamic changes in spinal alignment during activities of daily life.PURPOSEEstimate representative dynamic ranges of spinal alignment during gait among ASD patients using 3D motion tracking; compare dynamic alignment between mild and severe deformity patients and to healthy adults.STUDY DESIGN/SETTINGRetrospective review at a single institution.PATIENT SAMPLEFifty-two ASD patients and 46 healthy adults.OUTCOME MEASURESRadiographic alignment, kinematic spine motion, spatiotemporal gait measures, patient reported outcomes (VAS pain, ODI, SRS-22r).METHODSSpinal alignment was assessed radiographically and during standing and overground walking tests. Dynamic alignment was initialized by linking radiographic alignment to kinematic alignment during standing and at initial heel contact during gait. Dynamic changes in maximums and minimums during gait were made relative to initial heel contact for each gait cycle. Total range-of-motion (RoM) was measured for both ASD and healthy subjects. Dynamic alignment measures included coronal and sagittal vertical axes (CVA, SVA), T1 pelvic angle (TPA), lumbar lordosis (LL), and pelvic tilt (PT). ASD patient's deformities were classified as either Mild or Severe based on the SRS-Schwab ASD classification.RESULTSSevere ASD patients had significantly larger dynamic maximum and minimums for SVA, TPA, LL, and PT (all p<.05) compared with Mild ASD patients. ASD patients exhibited little difference in dynamic alignment compared with healthy subjects. Only PT had a significant difference in dynamic RoM compared with healthy (p<.001).CONCLUSIONSMild and Severe ASD patients exhibited similar global dynamic alignment measures during gait and had comparable RoM to healthy subjects except with greater PT and reduced spatiotemporal performance which may be key compensatory mechanisms for dynamic stabilization.     

An opt-out model for kidney transplant referral: The time has come

Disparities that affect equity in access to kidney transplantation for patients with kidney failure have been well described. Many robust clinical trials have tested the effectiveness of interventions to reduce disparities and equilibrate access to kidney transplantation. Moreover, policy changes have been enacted to achieve the same aims. Despite these efforts, rates of kidney transplant waitlisting within the first year of end-stage kidney disease have remained unchanged over the past 2 decades, while incident rates of end-stage kidney disease have climbed. Because prior interventions have not durably increased transplant access, disruptive change is clearly needed. The Advancing American Kidney Health Executive Order sets bold goals to transform kidney care for patients and caregivers. In this spirit, we discuss an Opt-Out for Transplant Referral Model as a compelling solution to improve equity in access to kidney transplantation.