Low DHEAS levels are associated with depressive symptoms in elderly Chinese men: results from a large study

This study investigated the association between depressive symptoms in elderly Chinese men and the total testosterone, dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), oestradiol and sex hormone-binding globulin (SHBG) levels, and the free androgen index. Cross-sectional data from 1147 community-dwelling elderly men, aged 65 and older, were used. Depressive symptoms were measured using the Chinese Geriatric Depression Scale (GDS). Total testosterone, free testosterone, DHEA, DHEAS, total oestradiol, the free androgen index and SHBG levels were assessed. DHEA was significantly associated with GDS score, and there was a trend towards DHEAS association, but this was not significant (β=-0.110, P=0.015; β=-0.074, P=0.055). However, no association was seen between depressive symptoms and total testosterone levels, free testosterone levels, oestradiol levels or SHBG levels. In terms of the presence of clinically relevant depressive symptoms, there were no statistically significant differences between patients in the lowest quartile of sex steroid hormone levels and those in other quartiles of sex steroid hormone levels. Similarly to Western studies, our study shows that DHEA and DHEAS levels are associated with depressive symptoms.     

Psychotic symptoms in patients undergoing coronary artery bypass grafting and heart valve operation.

OBJECTIVE: Delirium on internal medicine and surgical wards of the general hospital is associated with several predisposing and precipitating factors as well as adverse outcomes. Whether psychosis, the symptom of delirium that may be recognized most promptly, is similarly associated with these factors and outcomes is largely unknown. METHODS: Eight thousand one hundred and thirty-nine consecutive patients undergoing coronary artery bypass grafting and/or heart valve operation were screened for preoperative predisposing factors and postoperative psychotic symptoms between January 1999 and July 2004. Data on per- and postoperative precipitating factors were collected in 4942 patients enrolled between January 2001 and July 2004. Data were examined using logistic regression to estimate odds ratios. RESULTS: The rate of severe psychotic symptoms was 2.1% (n=168). Higher age, renal failure, dyspnoea, heart failure, and left ventricle hypertrophy were independent preoperative predisposing factors. Peroperative hypothermia (<33 degrees C), hypoxemia, low hematocrit, renal failure, increased sodium, infection and stroke were independent precipitating factors. Psychotic symptoms were independently associated with a prolonged length of stay on the intensive care unit (odds ratio 7.8; 95% confidence interval 5.6-11), multi-organ failure or shock (3.2; 95% CI: 2.2-4.9), cardiopulmonary resuscitation (3.6; 95% CI: 2.1-6.2), and in-hospital death after surgery (2.1; 95% CI: 1.1-4.1). CONCLUSIONS: Psychotic symptoms are independently associated with several chronic and peroperative problems (including mild hypothermia during surgery), closely resembling those for delirium (with and without psychotic symptoms). Psychotic symptoms are also independently associated with adverse outcomes. Prompt diagnostic and therapeutic intervention aimed at the underlying problem may improve outcomes.     

Does Bone Resorption Stimulate Periosteal Expansion? A Cross‐Sectional Analysis of β‐C‐telopeptides of Type I Collagen (CTX), Genetic Markers of the RANKL Pathway,and Periosteal Circumference as Measured by pQCT

We hypothesized that bone resorption acts to increase bone strength through stimulation of periosteal expansion. Hence, we examined whether bone resorption, as reflected by serum β‐C‐telopeptides of type I collagen (CTX), is positively associated with periosteal circumference (PC), in contrast to inverse associations with parameters related to bone remodeling such as cortical bone mineral density (BMD_C). CTX and mid‐tibial peripheral quantitative computed tomography (pQCT) scans were available in 1130 adolescents (mean age 15.5 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC). Analyses were adjusted for age, gender, time of sampling, tanner stage, lean mass, fat mass, and height. CTX was positively related to PC (β = 0.19 [0.13, 0.24]) (coefficient = SD change per SD increase in CTX, 95% confidence interval)] but inversely associated with BMD_C (β = –0.46 [–0.52,–0.40]) and cortical thickness [β = –0.11 (–0.18, –0.03)]. CTX was positively related to bone strength as reflected by the strength‐strain index (SSI) (β = 0.09 [0.03, 0.14]). To examine the causal nature of this relationship, we then analyzed whether single‐nucleotide polymorphisms (SNPs) within key osteoclast regulatory genes, known to reduce areal/cortical BMD, conversely increase PC. Fifteen such genetic variants within or proximal to genes encoding receptor activator of NF‐κB (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) were identified by literature search. Six of the 15 alleles that were inversely related to BMD were positively related to CTX (p < 0.05 cut‐off) (n = 2379). Subsequently, we performed a meta‐analysis of associations between these SNPs and PC in ALSPAC (n = 3382), Gothenburg Osteoporosis and Obesity Determinants (GOOD) (n = 938), and the Young Finns Study (YFS) (n = 1558). Five of the 15 alleles that were inversely related to BMD were positively related to PC (p < 0.05 cut‐off). We conclude that despite having lower BMD, individuals with a genetic predisposition to higher bone resorption have greater bone size, suggesting that higher bone resorption is permissive for greater periosteal expansion. © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.     

Potential Adverse Effect of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) on Bisphosphonate Efficacy: An Exploratory Post Hoc Analysis From a Randomized Controlled Trial of Clodronate

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to have weak but beneficial effects on bone health, including fracture risk, but many epidemiological studies are likely confounded. We explored the relationship between NSAIDs and fracture risk in a post hoc analysis of a well-documented, randomized, placebo-controlled study of the bisphosphonate, clodronate, in which treatment reduced osteoporotic fracture risk by 23%. Concurrent medication use at baseline was used to identify those prescribed oral NSAIDs. Only verified, incident fractures were included in the analysis. A total of 1082 (20.8%) women reported use of NSAIDs at baseline. They were slightly, but significantly, younger (mean 79 versus 80 years, p = 0.004), heavier (mean 66.7 versus 64.7 kg, p < 0.001) than nonusers, with slightly higher femoral neck bone mineral density (FN-BMD, 0.66 versus 0.64 g/cm², p < 0.001). In an adjusted model, NSAID use was associated with a significant increase in osteoporotic fracture risk over the 3-year study period (hazard ratio [HR] 1.27; 95% confidence interval [CI], 1.01–1.62; p = 0.039). However, this increase in risk was not statistically significant in the placebo group (HR 1.11; 95% CI, 0.81–1.52). In women receiving clodronate, the effect of the bisphosphonate to reduce osteoporotic fracture risk was not observed in those receiving NSAIDs (HR 0.95; 95% CI, 0.65–1.41; p = 0.81) in contrast to those not using NSAIDs (HR 0.71; 95% CI, 0.58–0.89; p = 0.002). In a subset with hip BMD repeated at 3 years, BMD loss during clodronate therapy was greater in those women receiving NSAIDs than in nonusers (eg, total hip −2.75% versus −1.27%, p = 0.078; femoral neck −3.06% versus −1.12%, p = 0.028), and was not significantly different from that observed in women receiving placebo. The efficacy of the bisphosphonate, clodronate, to reduce fracture risk was largely negated in those receiving NSAIDs. Although the mechanism is unclear, this clinically significant observation requires exploration in studies of commonly used bisphosphonates. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Unexplained chronic fatigue and core conflictual relationship themes: A study in a chronically fatigued population

Objective. Unexplained fatigue syndromes are multidimensional phenomena that involve a constellation of symptoms. This paper explores whether typical relationship patterns are associated with self‐reported and clinically rated fatigue symptoms in chronically fatigued patients. Method. Relationship patterns were assessed by means of the core conflictual relationship theme (CCRT) method. This method examines transference patterns, and was applied to interview data collected from chronically fatigued patients (N=30). Chronic fatigue was assessed by means of a self‐report questionnaire and was also rated clinically. Results. Both self‐reported and clinically rated fatigue correlated with relationship themes. The intensity of fatigue related to the perception of others as not respecting and as negatively interfering. The typical reaction of the self to relationships consists of feeling disrespected, anger, passivity, and reduced feelings of self‐consistency. Conclusion. Patients' perception of interpersonal relationships as distressing may be pivotal in understanding these results. Implications for clinical intervention and future research are indicated.     

Dexamethasone decreases the pro- to anti-inflammatory cytokine ratio during cardiac surgery

Background. Cytokines regulate inflammation associated withcardiopulmonary bypass (CPB). Pro-inflammatory cytokines maycause myocardial dysfunction and haemodynamic instability afterCPB, but the release of anti-inflammatory cytokines is potentiallyprotective. We studied the effects of dexamethasone on pro-and anti-inflammatory cytokine responses during coronary arterybypass grafting surgery. Methods. Seventeen patients were studied: nine patients receiveddexamethasone 100 mg before induction of anaesthesia (group1) and eight patients acted as controls (group 2). Plasma levelsof tumour necrosis factor (TNF)-     

Does sucralfate reduce early side effects of pelvic radiation? A double-blind randomized trial.

STUDY AND METHODS: A double-blind placebo-controlled study randomized 108 patients to investigate the effect of sucralfate on gastrointestinal side effects of pelvic radiation. RESULTS: Overall, pelvic radiation with the administered doses and fields and performed according to nowadays technical standards, was well tolerated. Comparison of the mean scores and the peak reactions for radiotherapy discomfort, diarrhoea and number of stools per day in the 80 evaluable patients showed no statistically significant difference between sucralfate and placebo. CONCLUSION: Based on these results, the use of sucralfate can not be recommended as standard practice.     

Inhibition of the development of collagen-induced arthritis in rhesus monkeys by a small molecular weight antagonist of CCR5

OBJECTIVE: Collagen-induced arthritis (CIA) in the rhesus monkey is a nonhuman primate model of rheumatoid arthritis (RA). The close phylogenetic relationship between humans and the rhesus monkey makes this model useful for the preclinical safety and efficacy testing of new therapies that are inactive in animals more distinctly related to humans. In this study, we tested the therapeutic potential of a novel, small molecular weight antagonist of CCR5, SCH-X, in this model. METHODS: CIA was induced in 10 rhesus monkeys. The animals were allocated to receive SCH-X or saline as the control (n = 5 in each group). Treatment was initiated on the day of CIA induction and continued for 45 days. Monkeys were monitored before and 63 days after CIA induction for macroscopic signs of clinical arthritis, such as soft-tissue swelling and body weight. Furthermore, markers of inflammation and joint degradation were monitored to follow the disease course. RESULTS: Only 2 of 5 animals in the SCH-X-treated group displayed prominent soft-tissue swelling, compared with all 5 saline-treated monkeys. In addition to the suppression of joint inflammation, treatment with SCH-X resulted in a reduction in joint destruction, as demonstrated by lower rates of urinary excretion of collagen crosslinks, with confirmation by histology. Whereas in all saline-treated monkeys, marked erosion of joint cartilage was observed, this was absent in 4 of the 5 SCH-X-treated monkeys. CONCLUSION: The systemic effects of treatment with SCH-X were a suppressed acute-phase reaction (reduction in C-reactive protein level) in the 3 treated monkeys with CIA that remained asymptomatic, and an altered antibody response toward type II collagen. The results suggest that the CCR5 antagonist SCH-X might have a strong clinical potential for treatment during periods of active inflammation, as seen in RA.