CELL RESPIRATION STUDIES : II. A COMPARATIVE STUDY OF THE OXYGEN CONSUMPTION OF BLOOD FROM NORMAL INDIVIDUALS AND PATIENTS WITH INCREASED LEUCOCYTE COUNTS (SEPSIS; CHRONIC MYELOGENOUS LEUCEMIA).

1. The oxygen consumption of blood of normal individuals, when the hemoglobin is saturated with oxygen, is practically zero within the limits of experimental error of the microspirometer used. 2. The oxygen consumed in a microspirometer by the blood of patients with chronic myelogenous leucemia with a high white blood cell count, and of one with leucocytosis from sepsis, was proportional to the number of adult polymorphonuclear neutrophils in the blood. 3. No correlation could be made between the rate of oxygen absorption and the total number of white blood cells in the blood, or the total number of immature cells, or the number of red blood cells, or the amount of oxyhemoglobin. 4. The blood of patients with chronic myelogenous leucemia continued to use oxygen in the microspirometer longer than that of normal individuals, and the hemoglobin, in the leucemic bloods, became desaturated even though exposed to air. 5. In blood in which the bulk. of the cells were immature and the mature cells few, the oxygen consumption was lower than in blood in which the mature cells predominated. The rate of oxygen consumption of the immature cells was relatively low as compared to the mature. 6. The slower rate of oxygen absorption by the immature leucocytes in chronic myelogenous leucemia as compared to the mature cells, places them, in accord with Warburg''s reports, in the class of the malignant tissues in this respect rather than in the group of young or embryonic cells.     

Unstable SCFE: Review of Treatment Modalities and Prevalence of Osteonecrosis

Background

The treatment of unstable slipped capital femoral epiphysis (SCFE) is rapidly evolving with the ability to correct epiphyseal alignment using the modified Dunn technique. Adopting a new treatment method depends on confirming that it achieves its goals, produces few, nonserious complications with no lasting sequelae, and improves the natural history of the disorder compared with known treatment methods. As such, the rates of osteonecrosis and complications after current treatments of unstable SCFE must be compared with those of newer surgical techniques.

Questions/purposes

We therefore addressed the following questions: (1) What is the rate of osteonecrosis of the femoral head after treatment of unstable SCFE? (2) What treatment modalities have been used for unstable SCFE and (3) what are the reported complications?

Methods

We performed a systematic electronic literature search for the keywords unstable and slipped capital femoral epiphysis and identified 199 articles. Of these, 60 met our inclusion criteria. Fifteen articles were included for analysis.

Results

The literature concerning the treatment and results of unstable SCFE is retrospective Level IV data that suggest an overall rate of osteonecrosis of 23.9%. Multiple treatment modalities were used for unstable SCFE treatment with varying, inconsistently recorded complications over the reporting period.

Conclusions

We found limited data concerning the rate of osteonecrosis and complications after treatment of unstable SCFE. Considering recent widespread interest in the modified Dunn procedure and the possibility of iatrogenic osteonecrosis, there is a need for prospective studies to identify complications and establish outcome based on standardized scores for established and emerging treatments of unstable SCFE.     

Blocking CTGF/CCN2 reverses neural fibrosis and sensorimotor declines in a rat model of overuse-induced median mononeuropathy

Encapsulation of median nerves is a hallmark of overuse-induced median mononeuropathy and contributes to functional declines. We tested if an antibody against CTGF/CCN2 (termed FG-3019 or Pamrevlumab) reduces established neural fibrosis and sensorimotor declines in a clinically relevant rodent model of overuse in which median mononeuropathy develops. Young adult female rats performed a high repetition high force (HRHF) lever-pulling task for 18 weeks. Rats were then euthanised at 18 weeks (HRHF untreated), or rested and systemically treated for 6 weeks with either an anti-CCN2 monoclonal antibody (HRHF-Rest/FG-3019) or IgG (HRHF-Rest/IgG), with results compared with nontask control rats. Neuropathology was evident in HRHF-untreated and HRHF-Rest/IgG rats as increased perineural collagen deposition and degraded myelin basic protein (dMBP) in median nerves, and increased substance P in lower cervical dorsal root ganglia (DRG), compared with controls. Both groups showed functional declines, specifically, decreased sensory conduction velocity in median nerves, noxious cold temperature hypersensitivity, and grip strength declines, compared with controls. There were also increases of ATF3-immunopositive nuclei in ventral horn neurons in HRHF-untreated rats, compared with controls (which showed none). FG-3019-treated rats showed no increase above control levels of perineural collagen or dMBP in median nerves, Substance P in lower cervical DRGs, or ATF3-immunopositive nuclei in ventral horns, and similar median nerve conduction velocities and thermal sensitivity, compared with controls. We hypothesize that neural fibrotic processes underpin the sensorimotor declines by compressing or impeding median nerves during movement, and that inhibiting fibrosis using an anti-CCN2 treatment reverses these effects.     

Lindane stimulates neutrophils by selectively activating phospholipase C and phosphoinositide-kinase activity

The organochlorine insecticide lindane is a known activator of neutrophil responses. In this work we delineated the biochemical pathways by which lindane stimulates neutrophil oxidant production. Plasma membrane GTPase activity was not stimulated by lindane, ruling out a role for lindane-induced activation of G-proteins or G-protein coupled receptors, whereas inhibition of phospholipase C inhibited lindane-induced oxidant production. Together these data pointed to phospholipase C as the direct target of lindane activation. Type I phosphoinositide 3-kinase was not significantly activated by lindane and an inhibitor of phosphoinositide 3-kinases inhibited oxidant production by only 40%. Thus, Type I phosphoinositide 3-kinase played a minor role, if any, in lindane-induced oxidant production. Lindane stimulated an increase in phosphatidylinositol phosphate suggesting a Type II or III phosphotidylinositol 3-kinase or phosphatidylinositol 4-kinase activity was also stimulated.     

Intraarticular Abnormalities in Residual Perthes and Perthes-like Hip Deformities

Background  

Residual Perthes and Perthes-like hip deformities are complex and may encompass proximal femoral deformity, secondary acetabular dysplasia, and associated intraarticular abnormalities. These intraarticular abnormalities have not been well characterized but may influence surgical technique and treatment outcomes.     

Use of computerized assessment to predict neuropsychological functioning and emotional distress in patients with systemic lupus erythematosus

OBJECTIVE: Cognitive dysfunction and neuropsychiatric disturbance are common in systemic lupus erythematosus (SLE). This study addressed the ability of the Automated Neuropsychological Assessment Metrics (ANAM), a computerized cognitive testing battery consisting of cognitive subtests, a sleepiness rating scale, and a mood scale, to predict neuropsychological status in patients with SLE. METHODS: Sixty individuals with SLE and no overt neuropsychiatric symptoms were administered ANAM to determine its validity as a screening measure of cognitive dysfunction and emotional distress in SLE. RESULTS: Performance on ANAM was compared with results of a consecutively administered, 2-hour battery of traditional neuropsychological tests and the Beck Depression Inventory II (BDI-II). Individual ANAM cognitive test scores were significantly correlated with most neuropsychological tests, particularly those measuring psychomotor processing speed and executive functioning. Using logistic regression, ANAM cognitive subtests successfully predicted individuals with SLE who had probable versus no impairment after controlling for premorbid levels of cognitive ability. Sensitivity of group classification was 76.2% and specificity was 82.8%, with 80% correct classification overall. ANAM's ability to predict neuropsychological functioning remained even after controlling for subjective reports of depressed mood and current sleepiness. Further, the ANAM mood scale was significantly correlated with the BDI-II (r = 0.67, P < 0.001), indicating its potential future use as a screening tool for emotional distress. CONCLUSION: ANAM shows promise as a time- and cost-efficient tool for screening and monitoring cognitive and emotional functioning in SLE, and can indicate when a more thorough neuropsychological investigation is warranted.     

Determinants of quality of life in community-dwelling older adults: comparing three cut-offs on the excellent-to-poor spectrum

Purpose

The aim of this study was to identify modifications in health, economic and social determinants of quality of life (QoL) in community-dwelling older adults when using different cut-offs to defining favorable QoL.

Methods

Data of year 2011 annual assessment in 1003 older men and women from the Lc65+ cohort study were used. Overall QoL was self-rated as ‘excellent,’ ‘very good,’ ‘good,’ ‘fair,’ or ‘poor.’ To identify significant health (self-rated health, SF-12v2 physical and mental health), economic (financial situation), and social (living with others, being socially supported, emotional support, group activities participation) determinants of QoL, a cut-off was set at three different positions to define favorable QoL on the ‘excellent’ to ‘poor’ spectrum: at least ‘good’ (model 1); at least ‘very good’ (model 2); and ‘excellent’ only (model 3).

Results

In all three models, bivariable analyses indicated significant associations between QoL and at least one variable from each health, economic, and social dimension. In multivariable analyses, only health-related variables remained significantly associated with QoL in model 1. Model 3 additionally retained financial situation. In model 2, QoL was positively associated with physical health [odds ratio (OR) 1.10, p < 0.001], mental health (OR 1.12, p < 0.001), self-rated health (OR 2.43, p < 0.001), group activities participation (OR 1.43, p = 0.037), being socially supported (OR 1.58, p = 0.024), and not reporting financial difficulties (OR 1.76; p = 0.036).

Conclusions

Using different cut-offs to defining favorable QoL results in important changes in the number and type of significant health, economic and social determinants. A cut-off between ‘good’ and ‘very good’ appears to best reflect the multidimensional nature of QoL.