Prevalence of and risk factors for low bone mineral density in Japanese female patients with systemic lupus erythematosus

To examine the prevalence of and risk factors for low bone mineral density (BMD) (osteoporosis or osteopenia) in Japanese female patients with systemic lupus erythematosus (SLE). We performed BMD measurements by dual X-ray absorptiometry at the lumbar spine and the hip and collected basic and lifestyle-related, clinical and treatment characteristics among 58 SLE patients. Odds ratios (ORs) and their 95% confidence intervals (CIs) were assessed for associations between low BMD and selected factors among SLE patients. The mean BMD?±?SD was 0.90?±?0.17?g/cm² at the lumbar spine and 0.76?±?0.17?g/cm² at the hip. The prevalence of osteopenia (2.5 SD?<?T score?<?1 SD) was 50.0% and that of osteoporosis (T score?<?2.5 SD) was 13.8% in our SLE patients. After adjustment for age and disease duration, we found the number of deliveries (OR?=?5.58, 95% CI?=?1.31?C26.06; P?=?0.02) to be a risk factor for overall low BMD (T score?<?1 SD) and a maximal dosage of >50?mg/day of oral corticosteroids (OR?=?0.25, 95% CI?=?0.07?C0.91; P?=?0.035) as a preventive factor for low BMD at the lumbar spine. Reduced BMD, especially in spinal trabecular bone, was pronounced in Japanese female patients with SLE, particular in those with a history of delivery. A history of high-dose oral corticosteroids was associated with the preservation of BMD at the lumbar spine, however, further study is needed considering the limited sample size.     

Correlation study between osteoporosis and hematopoiesis in the context of adjuvant chemotherapy for breast cancer

This retrospective study attempts to establish if a correlation exists between osteoporosis and hematopoiesis before and after adjuvant chemotherapy in the context of non-metastatic breast cancer. Osteoporosis is interpreted both as a direct marker of osteoblastic decline and as an indirect marker of increased bone marrow adiposity within the hematopoietic microenvironment. Patients from the “Centre du Sein” at CHUV (Centre Hospitalier Universitaire Vaudois) undergoing adjuvant chemotherapy were included in this study. Evolution of blood counts was studied in correlation with the osteoporosis status. Toxicity of chemotherapy was coded according to published probability of febrile neutropenia. One hundred forty-three women were included: mean age 52.1?±?12.5 years, mean BMI (body mass index) 24.4?±?4.1. BMD (bone mineral density) scored osteoporotic in 32% and osteopenic in 45%. Prior to chemotherapy, BMD was positively correlated with neutrophil (p?<?0.001) and thrombocyte (p?=?0.01) count; TBS (trabecular bone score) was not correlated with blood count. After the first cycle of chemotherapy, an increase of one point in TBS correlated with a decrease of 57% on the time to reach leucocyte nadir (p?=?0.004). There was a positive correlation between BMD and risk of infection (p?<?0.001). Our data demonstrates an association between osteoporosis and lower blood counts in a younger cohort than previously published, extending it for the first time to neutrophil counts in females. Our results suggest that the healthier the bone, the earlier the lowest leucocyte count value, prompting further research on this area.     

Lymph node ratio is a powerful prognostic index in patients with stage III distal rectal cancer: a Japanese multicenter study

Purpose

The present study aims to define the prognostic impact of the lymph node ratio (LNR) in patients with stage III distal rectal cancer.

Methods

We analyzed data from 501 patients who underwent curative resection (total mesorectal excision, TME) for stage III distal rectal cancer at 12 institutions between 1991 and 1998. Patients were divided into four groups according to quartiles based on LNR.

Results

Among the 501 patients, 381 underwent TME with pelvic sidewall dissection (PSD). The median numbers of lymph nodes retrieved with and without PSD were 45 and 17, respectively (P?<?0.0001). Forty-nine patients with lymph node retrieved less than 12 were excluded from further analyses. Among various clinicopathological parameters, univariate analysis identified age (P?=?0.0059), histological grade (P?<?0.0001), depth of tumor invasion (P?=?0.0003), and number of positive nodes (P?<?0.0001) and LNR (P?<?0.0001) as prognostic factors. The Cox proportional hazards model revealed that age (P?=?0.014), histological grade (P?<?0.0001), depth of tumor invasion (P?=?0.0002), and LNR (group 3, P?=?0.0012; group 4, P?<?0.0001) were independent prognostic factors. When the American Joint Committee on Cancer (AJCC) seventh staging system was added as a covariate, both AJCC stage (P?<?0.0001) and LNR (P?<?0.0001) were independent prognostic factors.

Conclusions

Adding the LNR concept to the AJCC cancer staging system will improve accuracy in evaluating the nodal status of distal rectal cancer.     

Expression of circulating Semaphorin3A and its association with inflammation and bone destruction in rheumatoid arthritis

To determine the expression of Semaphorin3A (Sema3A) in rheumatoid arthritis (RA) patients, and analyze the correlation between serum Sema3A and the pathogenesis of RA. The concentration of serum Sema3A and its mRNA expression level were detected in RA patients. The association of serum Sema3A level with clinical and laboratory features of RA were analyzed. Serum Sema3A of 130 RA patients (15.89?±?8.58 ng/ml) was significantly higher than that of 150 HC (6.96?±?2.62 ng/ml) and 215 patients with other rheumatic diseases (P?<?0.05). Consistent with the serum level, the Sema3A mRNA level was also higher in RA patients’ PBMC than that in HC (1.8-fold increase, P?<?0.01). The serum level of Sema3A was correlated with platelet counts (r?=?0.229), ESR (r?=?0.172), RF (r?=?0.230), IgM (r?=?0.254) and Sharp score (r?=?0.254), and bone mineral density (BMD) of lumbar spine (r?=?0.263). Serum Sema3A was also fundamentally higher in AKA-, APF-, anti-CCP-positive groups compared with negative groups (P?<?0.05). The ROC curve showed that the optimum diagnostic cutoff value for Sema3A was 10.881 ng/ml. RF level and antibodies (anti-CCP, APF, AKA, and GPI) positive rates were significantly higher in Sema3A positive group. Sharp score was also higher, although without significance. The expression of Sema3A is significantly elevated in RA patients. The level of serum Sema3A is positively correlated with inflammatory factors (including ESR, IgM, and RF) and is associated with auto-antibody production and bone destruction.     

Dickkopf-1 (Dkk-1) serum levels in systemic sclerosis and rheumatoid arthritis patients: correlation with the Trabecular Bone Score (TBS)

The aim of this research was to determine any correlations between Dickkopf-1 serum levels (Dkk-1, a natural inhibitor of the Wnt signaling pathway promoting osteoclastogenesis) and the Trabecular Bone Score (TBS), in systemic sclerosis (SSc) and rheumatoid arthritis (RA) patients. It also aimed at determining any difference in Dkk-1 serum levels between SSc and RA patients and a control group (CNT) of healthy subjects. A prospective study was carried out in 60 SSc and 60 RA patients and 60 CNT. Dkk-1 serum levels were evaluated by the ELISA method (Quantikine Human Dkk-1 Immunoassay, R&D System, Minneapolis, USA). The severity of microvascular damage was evaluated by nailfold videocapillaroscopy (NVC patterns: “Early,” “Active,” “Late”), in the SSc patients. TBS analysis and bone mineral density (BMD, g/cm²) were measured in all patients/subjects. The SSc patients showed higher Dkk-1 serum levels than RA (p?<?0.004) and CNT (p?<?0.0001) patients. SSc patients, showing the “Late” NVC pattern had statistically higher Dkk-1 serum levels than patients with either the “Active” or “Early” (p?<?0.004) patterns. Only in the “Late” NVC pattern group of SSc patients was there a significant negative correlation between Dkk-1 and TBS values (p?<?0.0001). The increased Dkk-1 serum levels and decreased TBS values observed suggest a diffuse bone damage in SSc patients with advanced disease, as demonstrated by the concomitant presence of the “Late” NVC pattern. Moreover, the bone remodeling in SSc seems even higher than that in RA patients.     

Bone mineral density in familial Mediterranean fever

The aim of this study was to evaluate the bone mineral density (BMD) in familial Mediterranean fever (FMF) and to search the effects of genetic factors, family history of FMF and types of clinical attacks on BMD. Forty-four attack-free patients with FMF and 36 healthy voluntary subjects were included in the study. BMD measurements of lumbar spine and left proximal femur were performed by dual energy X-ray absorptiometry (DEXA). There was no statistically significant difference between patient and control groups regarding median values of lumbar BMD (P?=?0.06), lumbar T (P?=?0.08) and Z (P?=?0.12) scores, femoral neck BMD (P?=?0.13), femoral T (P?=?0.22) and Z (P?=?0.16) scores and total femur BMD (P?=?0.14), T (P?=?0.19) and Z (P?=?0.27) scores. Patients with negative FMF family history had significantly lower femoral neck BMD (P?=?0.018), femoral neck T (P?=?0.009) and Z (P?=?0.01) scores and total femur BMD (P?=?0.033) than patients with positive FMF family history. There was no significant difference among the groups regarding mutation characteristic and types of attacks in lumbar BMD, T and Z scores, femoral neck BMD, T and Z scores and total femur BMD, T and Z scores (P?>?0.05). We found that the bone loss of patients with FMF is not different from that of the controls. The increased bone loss in the patients with negative family history for FMF should be further investigated with larger patient groups taking into consideration of the risk factors related to family history for osteoporosis.     

Analysis of the functional muscle–bone unit of the forearm in patients with phenylketonuria by peripheral quantitative computed tomography

Bone disease in patients with phenylketonuria (PKU) is incompletely characterized. We therefore analyzed, in a cross-sectional study radius macroscopic bone architecture and forearm muscle size by peripheral quantitative computed tomography (pQCT) and muscle strength by hand dynamometry in a large cohort (n?=?56) of adolescent and adult patients with PKU aged 26.0?±?8.9 (range, 11.8–41.5) years. Data were compared with a reference population (n?=?700) from the DONALD study using identical methodology. We observed a significant reduction of cortical thickness (z-score ?1.01?±?0.79), Strength–Strain Index (SSI) (z-score ?0.81?±?1.03), and total bone mineral density (BMD) of the distal radius (z-score ?1.05?±?1.00). Mean muscle cross-sectional area (z-score ?0.98?±?1.19) and muscle grip force (z-score ?0.64?±?1.26) were also significantly reduced, indicating an impaired muscular system as part of the clinical phenotype of PKU. SSI positively correlated (r?=?0.53, P?<?0.001) with the corresponding muscle cross-sectional area in the reference population; however, the regression line slope in PKU patients was less steep (P?<?0.001), indicating that bone strength is not adequately adapted to muscle force. In conclusion, the radial bone in PKU patients is characterized by reduced bone strength in relation to muscular force, decreased cortical thickness, and impaired total BMD at the metaphyseal site. These alterations indicate a mixed bone defect in PKU, both of which are due to primary alterations of bone metabolism and to secondary alterations in response to neuromuscular abnormalities.     

Molecular and pathological studies in the posterior interosseous nerve of diabetic and non-diabetic patients with carpal tunnel syndrome

Aims/hypothesis

We sought to establish the molecular and pathological changes predisposing diabetic and non-diabetic patients to the development of carpal tunnel syndrome (CTS).

Methods

The posterior interosseous nerve (PIN) was biopsied in 25 diabetic and 19 non-diabetic patients undergoing carpal tunnel decompression for CTS. Detailed morphometric and immunohistological analyses were performed in the nerve biopsy.

Results

In diabetic patients median nerve distal motor latency was prolonged (p?<?0.05 vs non-diabetic patients), PIN myelinated fibre density (p?<?0.05), fibre area (p?<?0.0001) and axon area (p?<?0.0001) were reduced, the percentage of unassociated Schwann cell profiles (p?<?0.0001) and unmyelinated axon density (p?<?0.0001) were increased and the axon diameter was reduced (p?<?0.0001). Endoneurial capillary basement membrane area was increased (p?<?0.0001) in diabetic patients, but endothelial cell number was increased (p?<?0.01) and luminal area was reduced (p?<?0.05) in non-diabetic patients with CTS. There was no difference in the expression of hypoxia-inducible factor 1α between diabetic and non-diabetic patients with CTS. However, the expression of vascular endothelial growth factor A (VEGF) (p?<?0.05) and its receptors VEGFR-1 (p?<?0.01) and VEGFR-2 (p?<?0.05) was significantly increased in diabetic patients, particularly those with type 1 diabetes, and related to the severity of nerve fibre pathology.

Conclusions/interpretation

This study demonstrates increased nerve fibre and microvascular pathology in relation to enhanced expression of VEGF and its receptors in a non-compressed nerve in diabetic compared with non-diabetic patients with CTS. It therefore provides a potential molecular and pathological basis for the predisposition of diabetic patients to the development of CTS.     

Effects of atorvastatin on apelin, visfatin (nampt), ghrelin and early carotid atherosclerosis in patients with type 2 diabetes

To investigate the influence of atrovastatin treatment on carotid intima-media thickness (CIMT) and serum levels of novel adipokines, like apelin, visfatin (nampt), and ghrelin, in patients with type 2 diabetes mellitus (T2DM). 87 statin-free patients (50 males) with T2DM, aged 55–70, but without carotid atherosclerotic plaques were initially enrolled. CIMT was assayed in all participants by ultrasound. Patients were then treated with atorvastatin (10–80?mg) to target LDL?<100?mg/dl. Anthropometric parameters, blood pressure, glycemic and lipid profile, high-sensitivity CRP (hsCRP), insulin resistance (HOMA-IR), apelin, visfatin and ghrelin were measured at baseline and after 12?months. Atorvastatin treatment significantly improved lipid profile across with increased apelin (from 0.307?±?0.130?pg/ml to 1.537?±?0.427?pg/ml; P?<?0.001) and suppressed visfatin (from 21.54?±?10.14?ng/ml to 15.13?±?7.61?ng/ml; P?=?0.002) serum levels in our diabetic patients. Standard multiple regression analysis showed that the atorvastatin-induced increment in apelin was independently associated with changes in total cholesterol (β?=?–0.510, P?=?0.030) and LDL-cholesterol (β?=?–0.590, P?<?0.001) (R ²?=?0.449, P?=?0.014), while the reduction of visfatin concentration was independently associated with the change in hsCRP (β?=?0.589, P?<?0.001; R ²?=?0.256, P?=?0.006), after adjustment for age, sex and BMI. CIMT and ghrelin did not alter significantly after 12?months of atorvastatin treatment (NS). Among participants, high-dose (80?mg) rather than low-dose (10?mg) of atorvastatin treatment yielded greater (P?<?0.05) changes in apelin, visfatin and CIMT levels despite the final equivalent levels of LDL. Atorvastatin administration increased apelin and decreased visfatin serum levels significantly, without change of CIMT, in patients with T2DM. However, high-dose of atorvastatin exerted more favourable impact on adipokines and CIMT than low-dose. Our results implicate another important link between adiposity and atherosclerosis.     

Omega-3 Polyunsaturated Fatty Acids Increase Plasma Adiponectin to Leptin Ratio in Stable Coronary Artery Disease

Background

Growing evidence suggests a cardioprotective role of omega-3 polyunsaturated fatty acids (PUFA). However, the exact mechanisms underlying the effects of omega-3 PUFA in humans have not yet been fully clarified.

Purpose

We sought to evaluate omega-3 PUFA-mediated effects on adipokines in patients with stable coronary artery disease (CAD) undergoing elective percutaneous coronary intervention (PCI).

Methods

We conducted a prospective, double-blind, placebo-controlled, randomized study, in which adiponectin, leptin and resistin were determined at baseline, 3–5 days and 30 days during administration of omega-3 PUFA 1 g/day (n?=?20) or placebo (n?=?28).

Results

As compared to controls administration of omega-3 PUFA resulted in increase of adiponectin by 13.4 % (P?<?0.0001), reduction of leptin by 22 % (P?<?0.0001) and increase of adiponectin to leptin (A/L) ratio by 45.5 % (P?<?0.0001) at 30 days, but not at 3–5 days. Compared with placebo adiponectin was 12.7 % higher (P?=?0.0042), leptin was 16.7 % lower (P?<?0.0001) and A/L ratio was 33.3 % higher (P?<?0.0001) in the omega-3 PUFA group at 30 days. Resistin decreased similarly in both groups after 1 month, without intergroup differences (P?=?0.32). The multivariate model showed that the independent predictors of changes in adiponectin at 1 month (P?<?0.001) were: omega-3 PUFA treatment, baseline platelet count, total cholesterol and those in leptin (P?<?0.0001) were: omega-3 PUFA treatment and waist circumference. Independent predictors of A/L ratio changes (P?<?0.0001) were: assigned treatment, current smoking and hyperlipidemia.

Conclusions

In high risk stable coronary patients after PCI omega-3 PUFA supplementation improves adipokine profile in circulating blood. This might be a novel, favourable mechanism of omega-3 PUFA action.     

Derangement of hemostasis in rheumatoid arthritis: association with demographic, inflammatory and metabolic factors

Disturbance of fibrinolysis is common in rheumatoid arthritis (RA), and it may be associated with the increased cardiovascular risk observed in this population. We aimed to assess coagulation derangement and investigate whether abnormalities are influenced by demographic, inflammatory or metabolic factors in patients with RA. Levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1), fibrinogen, prothrombin fragment 1?+?2 (PF1?+?2), thrombomodulin (TM), protein C and Von Willebrand factor (vWF) were compared between 141 RA patients and 50 healthy hospital controls. Within RA, coagulation factors were assessed alongside several demographic, inflammation and metabolic indicators. RA patients had higher levels of coagulation factors than controls. After correction for age and sex, having RA predicted increased tPA (B?=?0.15, P?<?0.001), PAI-1 (B?=?0.21, P?<?0.001), fibrinogen (B?=?0.86, P?<?0.001), PF1?+?2 (B?=?0.20, P?<?0.001), and TM (B?=?0.01, P?=?0.03) levels. CRP correlated positively with tPA (P?<?0.05), fibrinogen (P?<?0.001), TM (P?<?0.05), PF1?+?2 (P?<?0.001) and vWF (P?<?0.001). Metabolic factors linked with coagulation factors were hypertriglyceridaemia (tPA, P?<?0.05; PAI-1, P?<?0.05; protein C, P?<?0.05) and insulin resistance (tPA, P?<?0.01; PAI-1, P?<?0.01; vWF, P?<?0.05). Imbalance of coagulation and fibrinolytic mechanisms is common in RA and associates with age, inflammation, and metabolic factors. Further studies may determine whether these abnormalities are the consequence of acute inflammation or markers of vascular dysfunction.     

Osteoprotegrin interacts with biomarkers and cytokines that have roles in osteoporosis,skin fibrosis,and vasculopathy in systemic sclerosis: A potential multifaceted relationship between OPG/RANKL/TRAIL and Wnt inhibitors

Abstract

Objectives: We explored the interactions of osteoprotegerin (OPG) with biomarkers of bone turnover and cytokines, including soluble receptor activator for nuclear factor kappa beta ligand (sRANKL), tumor necrosis factor-related apoptosis-induced ligand (TRAIL), and Wnt inhibitors in osteoporosis, vasculopathy and fibrosis related to systemic sclerosis (SSc).

Methods: The study included 46 SSc patients and 30 healthy controls. Skin thickness, pulmonary fibrosis and/or hypertension, digital ulcers, and calcinosis cutis of SSc patients were assessed. We determined bone mineral density (BMD), and OPG, sRANKL, TRAIL, secreted frizzled-related protein 1 (sFRP-1), Dickkopf-related protein 1 (DKK-1), sclerostin in the serum of both patients and controls.

Results: OPG, sclerostin, and sFRP-1 levels were similar between patients and controls (P?>?0.05). Femoral neck and lumbar spine BMD and vitamin D levels were lower, and the OC, NTX, sRANKL, DKK1 and TRAIL levels were significantly higher, in patients than in controls (p?<?0.05). In subgroup analysis, patients with higher modified Rodnan skin score (mRodnan) had higher DKK-1, sclerostin, and TRAIL levels (p?<?0.05); those with diffuse SSc subtype had lower BMD values than those with limited SSc (p?<?0.05). Skin and pulmonary fibrosis linked negatively with BMD measures.

Conclusion: we showed that sRANKL levels were higher and correlated with bone turnover markers. It may be related to osteoporosis in SSc. The OPG level was unaltered in SSc patients. Higher TRAIL levels associated with skin thickness may indicate vascular dysfunction or injury. Higher DKK-1 and sclerostin levels may be related to a reactive increase in cells and be prominently linked to fibrosis in SSc.     

The effect of renal hyperfiltration on urinary inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes mellitus

Aims/hypothesis

High intraglomerular pressure causes renal inflammation in experimental models of diabetes. Our objective was to determine whether renal hyperfiltration, a surrogate for intraglomerular hypertension, is associated with increased excretion of urinary cytokines/chemokines in patients with type 1 diabetes mellitus.

Methods

Blood pressure, renal haemodynamic function (inulin and para-aminohippurate clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively) and urine samples were obtained during clamped euglycaemia in individuals with type 1 diabetes with either hyperfiltration (GFR determined using inulin [GFR_INULIN] ≥135 ml? min^?1 1.73 m^?2, n?=?28) or normofiltration (n?=?21) and healthy control individuals (n?=?18).

Results

Baseline clinical characteristics, dietary sodium and protein intake and blood pressure levels were similar in the diabetic and healthy control groups. In addition, HbA_1c levels were similar in the two diabetic groups. As expected baseline GFR was higher in hyperfilterers than either normofiltering diabetic patients or healthy control patients (165?±?9 vs 113?±?2 and 116?±?4 ml min^?1 1.73 m^?2, respectively, p?<?0.01). ERPF and renal blood flow were also comparatively higher and renal vascular resistance was lower in hyperfiltering patients (p?<?0.01). Hyperfiltering diabetic patients had higher excretion rates for eotaxin, IFNα2, macrophage-derived chemokine, platelet-derived growth factor (PDGF)-AA, PDGF-AB/BB and granulocyte-macrophage colony-stimulating factor (p?≤?0.01). Urinary monocyte chemoattractant protein (MCP)-1 and RANTES (regulated on activation, normal T expressed and secreted) excretion was also higher in hyperfiltering vs normofiltering diabetic individuals (p?<?0.01) and fibroblast growth factor-2, MCP-3 and CD40K excretion was elevated in hyperfiltering diabetic individuals vs healthy controls (p?<?0.01).

Conclusions/interpretation

Renal hyperfiltration is associated with increased urinary excretion of inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes.     

Relationship between non-enzymatic glycosylation and changes in serum insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 levels in patients with type 2 diabetes mellitus

The possible occurrence of increased non-enzymatic glycosylation of serum insulin-like growth factor binding protein-3 (IGFBP-3) in vivo and the changes that would simultaneously occur in serum levels of IGFBP-3 and insulin-like growth factor-1 (IGF-I) were investigated. We measured levels of IGF-I and IGFBP-3 and the degree of glycation of total serum protein and IGFBP-3, in serum samples obtained from patients with poorly controlled non-insulin-dependent diabetes (type 2) and from age-matched non-diabetic controls. Type 2 diabetic patients had significantly higher glycated serum protein (GlyP) levels. GlyP significantly correlated with age in the control (r = 0.315, P<0.05) but not in the type 2 diabetes group. Control and diabetic subjects had comparable serum IGF-I levels and in both groups IGF-I levels tended to decrease with age (r = –0.567, P<0.001 and r = –0.465, P<0.05 for control and type 2 diabetic subjects, respectively). In the type 2 diabetes group, IGF-I levels showed a negative correlation with serum GlyP values (r = –0.476, P<0.05). Type 2 diabetic and control patients had comparable serum IGFBP-3 levels, which were significantly higher in diabetic patients in the older age subgroups. A negative correlation was found between IGFBP-3 levels and age in the control (r = –0.705, P<0.001) and in the type 2 diabetes groups (r = –0.463, P<0.05). A significant negative correlation was found between IGFBP-3 levels and GlyP in control (r = –0.449, P<0.002) but not in type 2 diabetic subjects. The mean glycated IGFBP-3 (GlyIGFBP-3) levels were higher in the oldest type 2 diabetic patients. In these patients, GlyIGFBP-3 was negatively associated with IGF-I levels (r = –0.447, P<0.05). The IGF-I/IGFBP-3 molar ratio was significantly reduced in the 46–60-year-old type 2 diabetic group, whereas the IGF-I/IGFBP-3 ratio was positively and significantly correlated with GlyP levels only in the control group (r = 0.489, P<0.01). Our results show that: a) increased non-enzymatic glycosylation of IGFBP-3 occurs in vivo; and b) this effect is accompanied by an increase in IGFBP-3 levels. These results suggest that the IGF-I/IGFBP-3 system is another target for the metabolic derangements of type 2 diabetes. Its alterations might play a role in diabetic complications. Received: 22 September 1997 / Accepted in revised form: 30 April 1998     

Increased frequency of temporal acoustic window failure in rheumatoid arthritis: a manifestation of altered bone metabolism?

Assessment of intracranial vessels includes transcranial Doppler (TCD). TCD performance requires intact temporal acoustic windows (TAW). Failure of TAW (TAWF) is present in 8–20% of people. There have been no reports on TAWF in rheumatoid arthritis (RA). Altogether, 62 female RA patients were included. Among them, 20 were MTX-treated and biologic-free, 20 received infliximab, and 22 tocilizumab. The controls included 60 non-RA women. TAWF, temporal bone thickness, and texture were determined by ultrasound and CT. BMD and T-scores of multiple bones were determined by DEXA. Several bone biomarkers were assessed by ELISA. In RA, 54.8% of the patients had TAWF on at least one side. Neither TAW could be identified in 34% of RA subjects. In contrast, only 20.0% of control subjects had TAWF on either or both sides (p?<?0.001). In RA vs controls, 53.0 vs 2.9% of subjects exerted the trilayer, “sandwich-like” structure of TAW (p?<?0.001). Finally, in RA vs controls, the mean temporal bone thickness values of the right TAW were 3.58?±?1.43 vs 2.92?±?1.22 mm (p?=?NS), while those of the left TAW were 4.16?±?1.56 vs 2.90?±?1.16 mm (p?=?0.001). There was close association between TAWF, bone thickness, and texture (p?<?0.05). These TAW parameters all correlated with age; however, TAW failure and texture also correlated with serum osteoprotegerin. TAW bone thickness inversely correlated with hip BMD (p?<?0.05). TAWF, thicker, and heterogeneous temporal bones were associated with RA. These features have been associated with bone loss and OPG production. Bone loss seen in RA may result in OPG release and stimulation of bone formation around TAW.     

Bone mineral density in Iranian patients with inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) are at increased risk of developing osteopenia and osteoporosis. The aim of the study was to investigate the prevalence of decreased bone density and related risk factors in Iranian IBD patients. A total of 126 ulcerative colitis (UC) and 39 Crohn’s disease (CD) patients were enrolled. Dual-energy x-ray absorptiometry technique was used to measure bone density, and blood samples were obtained to measure biochemical markers. To find predictive variables for bone mineral density (BMD), stepwise regression analysis was carried out. A total of 53 IBD patients (32.1%) had diminished bone mineral density at either lumbar spine (L1–L4) or femoral neck. Of these, 9 (5.4%) had osteoporosis; however, 44 (26.7%) were osteopenic. Femoral neck bone density was significantly decreased among CD patients (p<0.04). There was no significant difference in BMD between men and women. We have found significant differences in BMD T scores at lumbar L1–L4, L2–L4, and femoral neck in corticosteroid ever-users (p<0.002, p<0.001, p<0.003, respectively). There was no significant difference in biochemical markers between UC and CD patients, except that more CD patients were hypocalcemic (p<0.001). Stepwise regression analysis has revealed lumbar spine T score was predicted by age (p<0.0001), corticosteroid use (p<0.002), and body mass index (BMI) (p<0.005); however, femoral neck was predicted by age (p<0.0001), BMI (p<0.0001), smoking (p<0.009), and corticosteroid use (p<0.028). Low bone density in Iranian UC and CD patients is in accordance with Western societies. Treatment with corticosteroid has increased this possibility in both groups. Corticosteroid use, age, smoking, and BMI are predictive factors for low bone density.     

Remote ischemic preconditioning regulates HIF-1�� levels, apoptosis and inflammation in heart tissue of cardiosurgical patients: a pilot experimental study

Transient episodes of ischemia in a remote organ (remote ischemic preconditioning, RIPC) bears the potential to attenuate myocardial injury, but the underlying mechanisms are only poorly understood. In the pilot experimental study presented we investigated cellular and molecular effects of RIPC in heart tissue of cardiosurgical patients with cardiopulmonary bypass (CPB) and focussed on apoptotic events, local and systemic inflammation as well as the regulation of the hypoxia induced factor-1?? (HIF-1??). RIPC was induced by four 5-min cycles of transient upper limb ischemia/reperfusion using a blood-pressure cuff. Right atrial tissue and serum were obtained from patients receiving RIPC (N?=?32) and control patients (N?=?29) before and after CPB. RIPC patients showed reduced troponin T serum concentrations in the first 48?h after surgery (P?<?0.05 vs. control) indicating cardioprotective effects of RIPC. Samples from RIPC patients that were collected before CPB contained significantly increased amounts of HIF-1?? and procaspase-3 (HIF-1??: P?<?0.05 vs. control, procaspase-3: P?<?0.05 vs. control), whereas activities of caspases 3 and 7 were by trend reduced. Samples from RIPC patients that were taken after CPB showed an increased activity of myeloperoxidase (P?<?0.05 vs. control; P?<?0.05 vs. RIPC before CPB) as well as elevated tissue concentrations of the interleukin (IL)-1?? (P?<?0.05 vs. RIPC before CPB). Serum levels of IL-8, IL-1?? and TNF?? were significantly increased in RIPC patients before CPB (P?<?0.05 vs. control before CPB). In summary, RIPC regulates HIF-1?? levels, apoptosis and inflammation in the myocardium of cardiosurgical patients and leads to increased concentrations of circulating cytokines.     

Assessment of multimedia-supported intervention in Muslim diabetic patients treated with insulin

This study aimed to evaluate the effect on diabetic care of an educational DVD in Jawi, the primary spoken language of Muslims in the study area, and pharmacist intervention among Muslim patients with diabetes treated with insulin. Type 2 diabetes Muslim patients on insulin treatment and poor glycemic control (N?=?143) in one hospital in southern Thailand were recruited to participate in a 6-month-period pre- and post-intervention study. For the intervention, the pharmacist provided the patients with education using a DVD and then asked them to show how to use insulin injection. Afterward, the pharmacist would correct the techniques for patients individually. At 6 months after intervention, significant reductions in glycated hemoglobin (HbA_1c) (8.31?±?1.40 to 7.19?±?1.15 %, P?<?0.001), fasting blood glucose (FBG) (195.06?±?86.14 to 115.81?±?11.48 mg/dL, P?<?0.001), systolic blood pressure (130.62 to 126.57 mmHg, P?=?0.004), triglycerides (183.36?±?90.48 to 182.31?±?90.68 mg/dL, P?<?0.001), and total cholesterol (199.57?±?68.77 to 194.97?±?64.77 mg/dL, P?=?0.006) were detected in patients who received the intervention. Increased low-density lipoprotein cholesterol (LDL-C) level (P?=?0.028) but no significant change in high-density lipoprotein cholesterol (HDL-C) were found (P?=?0.900). Moreover, medication adherence, diabetes knowledge, and skill in using insulin injection improved at the end of the study (P?<?0.001). In conclusion, the combination of language-specific educational DVD and pharmacist intervention appears to improve the short-term outcomes of diabetes care in Muslim patients on correctional insulin therapy.     

Treatment of osteopenia

The majority of osteoporotic fractures happen in individuals with BMD t-scores in the osteopenic range (?2, 5< t-score <?1). However, widespread use of anti-osteoporotic medication in this group based on t-score alone is not advisable because: 1) the number needed to treat is much higher (NNT?>?100) than in patients with fractured and t-score below ?2,5 (NNT 10?C20); 2)while specific osteoporosis treatments have demonstrated significant reductions of the fracture risk in patients with t-score <?2, 5, the efficacy in patients in the osteopenic range is less well established. Therefore, an osteopenic t-score does not in itself constitute a treatment imperative. Generally, osteopenia has to be associated with either low energy fracture(s) or very high risk for future fracture as assessed with risk calculators like FRAX to warrant specific osteoporosis therapy. Vertebral fractures are now conveniently assessed using lateral x-rays from DXA machines. In the vast majority of cases antiresorptive treatments (mainly hormone replacement therapy and SERMS in younger and bisphosphonates or Denosumab in older women) are the treatments of choice in this group of patients,??only rarely is anabolic therapy indicated.     

Increased serum levels of adhesion molecules ICAM-1 and VCAM-1 in systemic sclerosis are not specific for pulmonary manifestations

Studies suggest elevated serum intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) levels may be markers of pulmonary arterial hypertension in systemic sclerosis (SSc-PAH). We sought to evaluate whether ICAM-1 and VCAM-1 levels are useful screening biomarkers for incident SSc-PAH. In this cross-sectional study, four groups were selected from the Australian Scleroderma Cohort Study: group 1 (n?=?15) had definite PAH; group 2 (n?=?19) had interstitial lung disease (ILD); group 3 (n?=?30) were SSc-controls; and group 4 (n?=?34) were healthy controls. Serum ICAM-1 and VCAM-1 levels were measured using the Millipore Milliplex MAP Human 2-Plex Panel. There were no differences in ICAM-1 levels in the PAH versus ILD group (263.0?±?85.4 vs 380.4?±?168.3 ng/mL, p?=?0.136), SSc-controls (263.0?±?85.4 vs 253.1?±?98.0 ng/mL, p?=?1.00), or healthy controls (263.0?±?85.4 vs 201.8?±?57.2 ng/mL, p?=?0.093). Similarly, there were no differences in VCAM-1 level in PAH versus ILD groups (1476.2?±?434.9 vs 1424.8?±?527.6 ng/mL, p?=?1.00) and SSc-controls (1476.2?±?434.9 vs 1409.5?±?341.1 ng/mL, p?=?1.00). SSc subjects had significantly higher levels of ICAM-1 (297.4?±?134.0 vs 201.8?±?57.2 ng/mL, p?<?0.0001) and VCAM-1 compared to healthy controls (1432.7?±?427.4 vs 1125.6?±?273.4 ng/mL, p?<?0.0001). Neither ICAM-1 nor VCAM-1 is a specific screening biomarker of SSc-PAH. Instead, increased levels of these adhesion molecules in SSc, irrespective of pulmonary complications, suggest that they may play a role in SSc pathogenesis.