Alterations in intervertebral disc composition,matrix homeostasis and biomechanical behavior in the UCD‐T2DM rat model of type 2 diabetes

Type 2 diabetes (T2D) adversely affects many tissues, and the greater incidence of discogenic low back pain among diabetic patients suggests that the intervertebral disc is affected too. Using a rat model of polygenic obese T2D, we demonstrate that diabetes compromises several aspects of disc composition, matrix homeostasis, and biomechanical behavior. Coccygeal motion segments were harvested from 6‐month‐old lean Sprague‐Dawley rats, obese Sprague‐Dawley rats, and diabetic obese UCD‐T2DM rats (diabetic for 69 ± 7 days). Findings indicated that diabetes but not obesity reduced disc glycosaminoglycan and water contents, and these degenerative changes correlated with increased vertebral endplate thickness and decreased endplate porosity, and with higher levels of the advanced glycation end‐product (AGE) pentosidine. Consistent with their diminished glycosaminoglycan and water contents and their higher AGE levels, discs from diabetic rats were stiffer and exhibited less creep when compressed. At the matrix level, elevated expression of hypoxia‐inducible genes and catabolic markers in the discs from diabetic rats coincided with increased oxidative stress and greater interactions between AGEs and one of their receptors (RAGE). Taken together, these findings indicate that endplate sclerosis, increased oxidative stress, and AGE/RAGE‐mediated interactions could be important factors for explaining the greater incidence of disc pathology in T2D. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:738–746, 2015.     

Interaction of Propofol and Sevoflurane on Loss of Consciousness and Movement to Skin Incision during General Anesthesia

Background: Loss of consciousness (LOC) and immobility to surgical incision seem to be mediated at different levels of the central nervous system. Pharmacologic studies of hypnotic agents have previously focused on combinations of either volatile or intravenous anesthetics. This study examined the combination of inhaled sevoflurane and intravenous propofol at these two clinically relevant anesthetic end points.

Methods: Thirty-six elective surgical patients were initially enrolled. Conditions approximating steady state were obtained for sevoflurane and target-controlled propofol infusions. Patients were sequentially evaluated for LOC (loud voice plus mild prodding) and immobility to surgical incision. The study was designed using the Dixon up-down method.

Results: The observed propofol effect target with 50% response plus sevoflurane (0.46% end-tidal concentration) was 1.2 [mu]g/ml (95% confidence interval, 1.1-1.3 [mu]g/ml). It was not significantly different from that predicted (1.5 [mu]g/ml; 95% confidence interval, 1.2-1.7 [mu]g/ml) by simple additivity. The effective plasma concentration of propofol that suppressed movement to skin incision in 50% of patients was 5.4 [mu]g/ml (95% confidence interval, 4.8-6.0 [mu]g/ml) plus sevoflurane (0.86%) and was not significantly different from that predicted by additivity (5.4 [mu]g/ml; 95% confidence interval, 4.8-5.9 [mu]g/ml). Both analyses had adequate power (90%) to detect a significant change (+/-19 to 25%) from predicted value. Repeated-measures analysis of variance identified a Bispectral Index value of 70 as the break point between those who responded at LOC or did not.     

Racial Disparities in Eligibility for Preemptive Waitlisting for Kidney Transplantation and Modification of eGFR Thresholds to Equalize Waitlist Time

BackgroundPatients may accrue wait time for kidney transplantation when their eGFR is ≤20 ml/min. However, Black patients have faster progression of their kidney disease compared with White patients, which may lead to disparities in accruable time on the kidney transplant waitlist before dialysis initiation.MethodsWe compared differences in accruable wait time and transplant preparation by CKD-EPI estimating equations in Chronic Renal Insufficiency Cohort participants, on the basis of estimates of kidney function by creatinine (eGFR_cr), cystatin C (eGFR_cys), or both (eGFR_cr-cys). We used Weibull accelerated failure time models to determine the association between race (non-Hispanic Black or non-Hispanic White) and time to ESKD from an eGFR of ≤20 ml/min per 1.73 m². We then estimated how much higher the eGFR threshold for waitlisting would be required to achieve equity in accruable preemptive wait time for the two groups.ResultsBy eGFR_cr, 444 CRIC participants were eligible for waitlist registration, but the potential time between eGFR ≤20 ml/min per 1.73 m² and ESKD was 32% shorter for Blacks versus Whites. By eGFR_cys, 435 participants were eligible, and Blacks had 35% shorter potential wait time compared with Whites. By the eGFR_cr-cys equation, 461 participants were eligible, and Blacks had a 31% shorter potential wait time than Whites. We estimated that registering Blacks on the waitlist as early as an eGFR of 24–25 ml/min per 1.73 m² might improve racial equity in accruable wait time before ESKD onset.ConclusionsPolicies allowing for waitlist registration at higher GFR levels for Black patients compared with White patients could theoretically attenuate disparities in accruable wait time and improve racial equity in transplant access.     

Studies on YKL-40 in knee joints of patients with rheumatoid arthritis and osteoarthritis. Involvement of YKL-40 in the joint pathology

OBJECTIVE: The presence of YKL-40 (human cartilage glycoprotein 39) in synovium, cartilage and synovial fluid (SF) from knee joints of patients with rheumatoid arthritis and osteoarthritis (OA) were related to histopathological changes in synovium and cartilage and to serum YKL-40 and other biochemical markers. METHODS: The localization of YKL-40 in synovium and cartilage was determined by immunohistochemistry. Synovial inflammation was estimated histologically and by magnetic resonance imaging (MRI). Biochemical markers of inflammation, neutrophil activation and cartilage metabolism were analysed. YKL-40 concentrations in serum and SF were determined by RIA and ELISA. RESULTS: In the synovium YKL-40 positive cells were found in lining and stromal cells (macrophages) and the number of YKL-40 positive cells was related to the degree of synovitis. In arthritic cartilage, YKL-40 was located to chondrocytes. YKL-40 levels in SF were higher in RA patients with moderate/severe or none/slight synovitis of the knee joint compared to OA patients with moderate/severe or none/slight synovitis. SF YKL-40 correlated with the synovial membrane and the joint effusion volumes determined by magnetic resonance imaging (MRI) and with other biochemical markers of intercellular matrix metabolism. SF YKL-40 was higher than serum YKL-40, and a relationship existed between the YKL-40 levels in SF and serum. Intraarticular glucocorticoid injection was followed by clinical remission and a decrease in serum YKL-40, which increased again at clinical relapse. CONCLUSIONS: YKL-40 in SF is derived from cells in the inflamed synovium, chondrocytes and SF neutrophils. Joint derived YKL-40 influences serum YKL-40. YKL-40 may be involved in the pathophysiology of the arthritic processes and reflect local disease activity.     

Relation between diagnoses on severity, sick leave and loss of job among patients with occupational hand eczema

BACKGROUND: Epidemiological studies indicate that occupational hand eczema (OHE) often is associated with persistent dermatitis and prolonged sick leave, which may lead to unemployment. Previous studies suggest that OHE caused by allergic contact dermatitis and atopic dermatitis (AD) carries the worst prognosis. OBJECTIVES: To evaluate and compare the severity and consequences of recognized OHE in different diagnostic and subdiagnostic groups. METHODS: Between October 2001 and November 2002, all new cases of recognized OHE were identified from the Danish National Board of Industrial Injuries Registry (758 cases). Severity was graded from 0 to 2 depending on the intensity of skin response and the frequency of relapse. To supplement the information from the Registry, we surveyed the study population using a postal questionnaire which included questions about disease duration, sick leave, current occupation and loss of job. RESULTS: The overall response rate to the questionnaire was 82%. We observed substantially greater severity among those with occupational irritant contact dermatitis (ICD) and AD than for any other diagnoses. Age above 50 years was also associated with increased severity of OHE. Prolonged sick leave due to OHE was reported by 19.9% and was associated with AD and severe OHE. We found a higher proportion of prolonged sick leave among those in food-related occupations (27.2%) compared with those in wet occupations (20.1%) and other occupations (16.5%). Twenty-three per cent reported that they had lost their job at least once during the past 12 months due to OHE. The only strong association with loss of job was food-related occupations. CONCLUSIONS: Occupational ICD and AD appear to be strongly associated with severity of OHE. AD and severity of OHE were independently associated with prolonged sick leave. Having a food-related occupation appears to be associated with increased risk of loss of job.     

Contact allergy to methyldibromo glutaronitrile--data from a 'front line' network

The preservative methyldibromo glutaronitrile (MDBGN) has caused an epidemic of contact allergy in Europe. However, most data concerning contact allergy comes from hospital departments of dermatology. As a part of the primary health care sector, Danish dermatologists in private practice provide the front line of care for patients with skin diseases. Data from this source may therefore better reflect trends in the general population than material from hospital departments of dermatology. In this study, the frequency of MDBGN allergy and the characteristics of patients seen by dermatologists in private practice were studied. In 1 year, 2146 patients were patch tested by the participating dermatologists from 4 clinics in various parts of Denmark. 5% (110) had positive patch tests to MDBGN, with no difference between the sexes. After adjustment was made for other background variables, multivariate analysis using logistic regression showed a significant association between hand eczema and MDBGN allergy (OR 2.5, P < 0.001). In 53 cases (52.4%), the patch test reaction to MDBGN was judged to be of current relevance. Creams and lotions accounted for 31% of the identified causative products and liquid soaps for 23%. It is concluded that contact allergy to MDBGN is frequent among patients seen by dermatologists in private practice. This is consistent with results from hospital departments of dermatology in Europe and indicates a general trend and ongoing epidemic in the general population. The significant relationship between hand eczema and MDBGN allergy is of concern, and the finding that wash-off products, especially liquid soaps, play a significant role in MDBGN allergy calls for a revision of the safety assessment of MDBGN in wash-off products.     

Deodorants: an experimental provocation study with isoeugenol

Axillary dermatitis is common and overrepresented in people with contact allergy to fragrances. Many people suspect their deodorants to be the incriminating products. In order to investigate the significance of isoeugenol in deodorants for the development of axillary dermatitis when used by people with and without contact allergy to isoeugenol, patch tests with deodorants and ethanol solutions with isoeugenol, as well as repeated open application tests (ROAT) with roll-on deodorants with and without isoeugenol at various concentrations, were performed in 35 dermatitis patients, 10 without and 25 with contact allergy to isoeugenol. A positive ROAT was observed only in patients hypersensitive to isoeugenol (P<0.001) and only in the axilla to which the deodorants containing isoeugenol had been applied (P<0.001). Deodorants containing isoeugenol in the concentration range of 0.0063-0.2% used 2 times daily on healthy skin can thus elicit axillary dermatitis within a few weeks in people with contact allergy to isoeugenol.     

The association between hand eczema and nickel allergy has weakened among young women in the general population following the Danish nickel regulation: results from two cross‐sectional studies

Background: An association between nickel contact allergy and hand eczema has previously been demonstrated. In 1990, Denmark regulated the extent of nickel release in the ear‐piercing process as well as nickel release from consumer products. Objectives: This study aimed to evaluate the effect of the Danish nickel regulation by comparing the prevalence of concomitant nickel allergy and hand eczema observed in two repeated cross‐sectional studies performed in the same general population in Copenhagen. Materials: In 1990 and 2006, 3881 18–69 year olds completed a postal questionnaire and were patch tested with nickel. Data were analysed by logistic regression analyses and associations were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Results: The prevalence of concomitant nickel contact allergy and a history of hand eczema decreased among 18–35‐year‐old women from 9.0% in 1990 to 2.1% in 2006 (P < 0.01). The association between nickel contact allergy and a history of hand eczema decreased in this age group between 1990 (OR = 3.63; CI = 1.33–9.96) and 2006 (OR = 0.65; CI = 0.29–1.46). Among older women, no significant changes were observed in the association between nickel contact allergy and hand eczema. Conclusions: Regulatory control of nickel exposure may have reduced the effect of nickel on hand eczema in the young female population.