Functional hyperprolactinemia and hypophyseal microadenoma in systemic sclerosis

OBJECTIVE: Hyperprolactinemia (HPRL) has been identified in more than half of patients with systemic sclerosis (SSc). However, the association with pituitary adenoma and the status of hypothalamic dopaminergic tone using metoclopramide (MTC) test has not been studied. We investigated the prevalence of prolactin (PRL)-secreting pituitary adenoma and evaluated production of PRL by dynamic testing with MTC in SSc. METHODS: We studied 30 patients with SSc (mean age 38 +/- 10 yrs) and 20 healthy controls (mean age 37 +/- 11 yrs). Serum PRL concentrations were determined by radioimmunoassay in all subjects, and PRL response was measured 30, 60, 90, and 120 min after injection of 10 mg of MTC. Computed tomography (CT) of the sella turcica was performed. RESULTS: The mean basal serum PRL levels before and after stimulation with MTC in SSc patients versus controls were: basal 18.2 +/- 5.4 versus 8.7 +/- 1.6 ng/ml, p = NS; 30 min: 175.0 +/- 5.4 versus 61.0 +/- 42 ng/ml, p < 0.001; 60 min: 160 +/- 64 versus 52 +/- 30 ng/ml, p < 0.001; 90 min: 125 +/- 57 versus 42 +/- 21.0 ng/ml, p < 0.05; 120 min: 108.0 +/- 57 versus 30.0 +/- 10 ng/ml, p < 0.005. CT scan showed microadenomas in 24/30 SSc patients and 1/20 controls (p = 0.001). CONCLUSION: Our study suggests that a group of patients with SSc have a high prevalence of HPRL with increased central dopaminergic tone, and microadenomas. PRL may have a role in the pathogenesis of SSc. Further studies are necessary to confirm our results.     

Neuron specific enolase concentration is increased in serum and decreased in platelets of patients with active systemic sclerosis

OBJECTIVE: To determine frequency, origin, and clinical associations of elevated serum neuron specific enolase (NSE) in systemic sclerosis (SSc). METHODS: Serum was obtained from 75 patients with SSc, 20 systemic lupus erythematosus, 8 polymyositis, 10 idiopathic interstitial lung disease, and 10 healthy volunteers. NSE status was determined in serum (in all individuals) and in platelet lysate (in volunteers and 30 patients with SSc). RESULTS: Elevated serum NSE (mean 22.6 ng/ml, range 12.1-68.2 ng/ml) was observed in 26 patients with SSc (34.6%). Those with diffuse SSc had higher serum NSE than those with limited disease (16.5 +/- 13.4 vs 9.6 +/- 5.0 ng/ml, p = 0.006). No association was found between serum NSE and lung or esophagus involvement. Patients with long-standing disease had lower serum NSE than those with early disease (10.8 +/- 7.3 vs 16.1 +/- 13.6 ng/ml, p = 0.05). Serum NSE was 19.4 +/- 13.0 ng/ml in patients with total skin score (TSS) > 20, 8.3 +/- 2.1 ng/ml in patients with TSS < 5, and 6.0 +/- 3.1 ng/ml in volunteers (p = 0.01). NSE platelet lysate concentration was 3.6 +/- 2.9 ng/ml in patients with TSS > 20, 12.4 +/- 4.1 ng/ml in those with TSS < 5, and 14.1 +/- 6.5 ng/ml in healthy individuals (p < 0.001). Volunteers and SSc patients with low TSS had comparable S/PL-NSE index (serum/platelet lysate NSE concentration) (0.42 +/- 0.16 and 0.75 +/- 0.33, respectively), both lower than SSc patients with high TSS (7.45 +/- 5.57) (p < 0.001). CONCLUSION: Elevated serum NSE was observed in one-third of SSc patients but not in other autoimmune rheumatic diseases. The inverse relationship between serum and platelet lysate NSE concentration suggests platelet activation as the origin of high serum NSE in SSc. NSE S/PL was the best discriminatory variable between healthy volunteers and SSc patients as well as between patients with high and low TSS. High serum NSE and high NSE-S/PL index seemed to be associated with SSc disease activity. Further work is warranted to investigate a possible role for this marker in assessing disease activity and therapy response.     

Serum adipokines levels in patients with systemic sclerosis: A meta-analysis

Background: Systemic sclerosis is an chronic inflammatory autoimmune diseases. Adipokine has been reported to play an important role in modulating immune responses. Recent studies suggest that adipokine also plays some roles in the pathogenesis of systemic sclerosis (SSc). However, published data regarding the relationship between plasma/serum adipokine levels and SSc are contradictory. The aim of this study was at performing a meta-analysis to derive a more accurate estimation and further investigate the association of plasma/serum leptin and adiponectin levels with SSc patients.

Methods: PubMed, and Web of Science databases (up to Feb 20, 2016) were used to obtain all relative published literatures. The study quality was assessed by the Newcastle–Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis.

Results: A total of fourteen studies were finally included in this meta-analysis. Among them, six of which were studied for the serum adiponectin levels in SSc patients, six of which were studied for the serum leptin levels in SSc patients, and two of them were studied both for serum adiponectin levels and serum leptin levels in SSc patients. The meta-analysis results showed that the serum adiponectin levels in SSc patients were significantly lower than that in normal controls (SMD = ?0.608?ng/ml, 95% CI = ?1.029 to ?0.186, p?=?0.005). However, there were no significant differences in serum leptin levels between SSc patients and healthy controls (SMD = ?0.990?ng/ml, 95% CI = ?2.340 to 0.359, p?=?0.150). The subgroup analysis showed that Asia SSc patients with age less than 50 years old had lower plasma/serum adiponectin levels when compared with controls.

Conclusion: The serum adiponectin levels, but not serum leptin levels, in SSc patients were significantly lower than that in normal controls.     

Correlation between serum prolactin levels and lupus activity

To assess the frequency of hyperprolactinemia and evaluate its possible clinical significance in patients with systemic lupus erythematosus (SLE). We determined serum prolactin (PRL) levels in 30 patients with SLE by a radioimmunometric assay. For each patient, the clinical disease activity was assessed using the Systemic Lupus Activity Measure. Antinuclear antibodies were determined by standard techniques. Correlation between PRL concentrations and SLE clinical and serological activity were evaluated. Elevated serum concentrations of PRL (>25 ng/ml in female and >16 ng/ml in male) were found in 10 of the 30 (33.3%) patients (7–85 ng/ml, mean 33.8, SD 19.8). A significant correlation was found between the PRL levels and the clinical disease activity of SLE (P < 0.001, r = 0.675). In addition, hyperprolactinemia was associated with serological activity. Hyperprolactinemia was frequently detected in patients with SLE. There is a significant correlation between hyperprolactinemia and lupus activity.     

Enhanced serum prolactin (PRL) in patients with systemic lupus erythematosus: PRL levels are related to the disease activity.

Recent accumulated evidence suggests that prolactin (PRL) is an important immunomodulator and plays a part in the pathogenesis of systemic lupus erythematosus (SLE). The current study assessed the frequency of hyperprolactinaemia in patients with SLE and its association with defined clinical manifestations or serological abnormalities. PRL levels were analysed in 60 patients with SLE including a follow-up of 20 patients, 18 patients with rheumatic autoimmune diseases other than SLE (AID) and in 47 normal healthy subjects (NHS) using ELISA. Clinical manifestations and disease activity (ECLAM) were recorded. Autoantibodies (anti-dsDNA, anti-CL) were determined by standard techniques. In all, 28.3% of the patients with SLE had raised serum PRL. Their PRL levels (17.4+/-15.1 ng/ml, P<0.0001) and those of patients with AID (13.1+/-10.3 ng/ml, P<0.001) were significantly higher compared to NHS (6.3+/-3.2 ng/ml). Anti-dsDNA (r(s) = 0.3, P = 0.04) and anti-CL antibody titres (IgG; r(s) = 0.3, P = 0.03) correlated with PRL level. Furthermore, elevated erytthrocyte sedimentation rate (ESR), anaemia, decrease in C3, fatigue, fever and renal involvement were associated with hyperprolactinaemia. These results were confirmed by follow-up examinations. Moderate hyperprolactinaemia is present in a subset of patients with SLE and serum PRL correlates with clinical and serological disease activity.     

Cross-sectional evaluation of YKL-40 serum concentrations in patients with systemic sclerosis. Relationship with clinical and serological aspects of disease

OBJECTIVE: To investigate the behavior of serum YKL-40 in a cohort of patients with systemic sclerosis (SSc). METHODS: Forty SSc patients (35 women, 5 men) were investigated for serum YKL-40, soluble interleukin 2 receptor alpha (sIL-2Ra; by ELISA), von Willebrand factor (vWF; ELISA), and aminoterminal propeptide of type III procollagen (PIIINP; radioimmunoassay) concentrations. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were evaluated. Skin and organ system involvement were scored according to the Medsger organ/system severity scale. RESULTS: Serum YKL-40 in SSc patients (mean 132.9 ng/ml; median 75.5, 95% CI 87.8-175) was significantly higher than in controls (mean 66.6 ng/ml; median 52, 95% CI 54.6-78.6). Fourteen patients had levels > 135 ng/ml (cutoff value) with a mean of 264.7 +/- 160 ng/ml. Serum YKL-40 values were found to be more frequently increased in patients with arthralgias/arthritis (18 cases) than in patients without such features (4/22) (p = 0.021). Significant differences were found comparing serum YKL-40 concentrations in the patients with or without joint involvement (median 138 vs 57.5 ng/ml, respectively; p = 0.007). Serum YKL-40 levels correlated with the joint involvement severity score (p = 0.018) and sIL-2Ra levels (p < 0.001). No differences were found with any therapeutic regimen. CONCLUSION: This preliminary study shows that YKL-40 serum levels are increased in SSc and that they are correlated with sIL-2Ra and joint involvement, suggesting a relationship with cartilage and/or fibroblast activity.     

Estimated glomerular filtration rate and renal resistive index as possible predictive markers of mortality in systemic sclerosis

ObjectiveSubclinical nephropathy is underestimated in systemic sclerosis (SSc). Study aim is to evaluate the role of renal resistance indices (RRI) and estimated glomerular filtration rate (eGFR) assessed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) as predictive markers of mortality during 10 years of follow-up in SSc patients.Methods181 SSc patients (60 years, 152 females) were enrolled. At baseline, the GFR was estimated in 181 SSc patients and RRI was measured in 122 SSc patients. During a follow-up of 10 years we recorded the main complications of disease, date and causes of death.ResultseGFR shows a linear negative correlation with RRI. RRI showed a correlation with systolic pulmonary artery pressure (sPAP). Overall survival is lower in SSc patients with eGFR<60 ml/min and RRI ≥0.70 than in SSc patients with eGFR≥60 ml/min (p<0.0001) and with RRI<0.70 (p<0.01) both for mortality due to SSc and all causes. In multivariate analysis, eGFR<60 ml/min [HR 6.429, 95%CI (1.006-41.08), p<0.05] and forced vital capacity (FVC) [HR 0.954, 95%CI (0.911-1), p<0.05] are predictive markers of mortality due to SSc, while eGFR [HR 3.617, 95%CI (1.370-9.554), p<0.01], RRI [HR 0.210, 95% CI (0.068-0.649), p<0.01], age [HR 1.062, 95%CI (1.023-1.103), p<0.01], FVC [HR 0.967, 95%CI (0.946-0.989), p<0.01] and disease activity index (DAI) [HR 1.663, 95%CI (1.262-2.191), p<0.0001] are predictive markers of mortality due to all causes.ConclusionWe demonstrate that eGFR is a predictive marker of mortality due to SSc and to all causes, conversely RRI is predictive marker of mortality due to all causes.     

Correlation of serum prolactin levels and disease activity in systematic lupus erythematosus

To assess the frequency of hyperprolactinaemia and its possible clinical significance in patients with systemic lupus erythematosus (SLE). In this cross-sectional study, we determined serum prolactin (PRL) levels in 60 SLE female patients (age range 15–60 years). Disease activity was defined according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Serum PRL concentrations were determined by immunoradiometric assay. Elevated serum concentrations of PRL (>20 ng/ml) were found in 5 of 60 (8.4%) patients. No direct correlation between PRL levels with disease activity of SLE was found (r = 0.062, P = 0.39). SLE was active in 23 patients (SLEDAI ≥ 6) and inactive in 37 (SLEDAI < 6). In those with active disease, median PRL levels were lower (11.0 ng/ml) than normoprolactinaemic group (12.1 ng/ml). There was no significant difference in serum PRL levels between active and non-active patients (P = 0.07). There was a significant difference in the frequency of several clinical manifestations and serological parameters between SLE patients with normal and high prolactin (renal involvement, haematological manifestation and anti-ds DNA). This study has shown that hyperprolactinaemia is prevalent in random SLE patients. The elevated PRL levels seem not to be associated with disease activity. The mechanism and pathoaetiological and clinical significance of hyperprolactinaemia in a small subset of SLE patients remain unclear and a longer follow-up is necessary.     

Incidence,prevalence and long-term progression of Goh algorithm rated interstitial lung disease in systemic sclerosis in two independent cohorts in flanders: A retrospective cohort study

Objectives: The epidemiology of interstitial lung disease (ILD) in systemic sclerosis (SSc) in Belgium is unknown. In literature, its prevalence varies between 19% and 52% in limited/diffuse cutaneous SSc (LcSSc/DcSSc). However, its prevalence in “early” SSc (pre-clinically overt SSc without [yet] skin involvement), nor its incidence rate in SSc (LcSSc/DcSSc/“early” SSc) has ever been described. Against this background, we aimed to determine the prevalence/incidence (rate) and progression of ILD in SSc.Methods: 12-year follow-up data of consecutive SSc patients, included in two Flemish cohorts (University Hospitals Ghent and Leuven), were retrospectively analysed. ILD was classified according to the simplified Goh algorithm. Progression of ILD was defined as a relative decline of FVC ≥10%, a combined relative decline of FVC 5-10% and DLCO ≥15%, or as an increase in HRCT extent.Results: 722 patients (60% LcSSc/ 20% DcSSc/ 20% “early” SSc, median (IQR) follow-up 39 [12-80] months) had baseline HRCT. 243 were rated to have ILD at baseline and 39 during follow-up (prevalence of 34%/ incidence rate of 20.3/1000PY, 95%CI:14.5-27.8). Amongst those with baseline ILD, 60% had lung functional progression at five years of follow-up. In the “early” SSc subgroup, eight patients were rated to have ILD at baseline and three during follow-up (prevalence of 6%/ incidence rate of 5.8/1000 PY, 95%CI:1.2-17.0).Conclusion: Both LcSSc and DcSSc patients should be monitored for ILD evolution. The low prevalence and incidence of ILD in the “early” SSc subgroup may instruct future decisions on the construction of uniform patient follow-up pathways in “early” SSc.     

Serum free prolactin concentrations in patients with systemic lupus erythematosus are associated with lupus activity

OBJECTIVE: To determine in patients with systemic lupus erythematosus (SLE) the relationships among serum total and free prolactin (PRL) levels, isoforms of PRL and lupus activity. METHODS: In a cross-sectional study, 259 patients with SLE were tested for serum total PRL, serum free PRL, and PRL in fractions obtained after gel filtration chromatography (in 70 sera taken at random) by immunoradiometric assay based on disease activity. RESULTS: A significant correlation between direct PRL and free PRL levels was found in patients with and without lupus activity (r = 0.475, P<0.001); however, this was less so for non-active patients than for active patients (r=0.433, P<0.001 and r=0.909, P<0.001, respectively). SLE Disease Activity Index (SLEDAI) scores correlated positively with serum free PRL levels (r=0.314, P<0.001) and percentage of little PRL (r=0.33, P=0.005) and negatively with percentage of big big PRL (r=-0.3, P=0.012). Patients with active disease had higher serum free PRL levels (median 12.6 vs 9.3 ng/ml, P<0.001), higher percentages of little PRL (83.1 +/- 21.2 vs 63.6 +/- 24.8%, P=0.011) and lower percentages of big big PRL (9.4 +/- 18.0 vs 25.2 +/- 24.3%, P=0.031). Different clinical manifestations and serological parameters of lupus disease activity were more frequent in patients with free hyperprolactinaemia than in patients with normal serum free PRL levels (such as neurological manifestations, renal involvement, serositis, haematological manifestations, anti-double-stranded DNA and hypocomplementaemia; P<0.021). CONCLUSION: An increase in serum free PRL levels, higher percentages of little PRL and lower percentages of big big PRL proved to be factors related to lupus activity in a subset of patients with SLE. These novel data must be taken into account in future studies aiming to establish a relationship between PRL and disease activity in SLE.     

Altered diurnal rhythm of prolactin in systemic sclerosis

OBJECTIVE: Mild hyperprolactinemia has been reported in systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). We investigated whether the elevated serum level of prolactin (Prl) detected in SSc is due to a sustained increase over 24 h and/or a shift in the diurnal rhythm, and whether Prl autoantibodies--originally described in SLE--may interfere in the assay. METHODS: The serum level of Prl was measured by ELISA and compared between 73 patients with SSc and 73 age and sex matched controls (78% women, age 56 +/- 11 years). The diurnal rhythms of Prl and thyrotropin (thyroid stimulating hormone, TSH) were compared between 3 patients with SSc and 10 healthy controls. Blood was taken at 2-3, 6-7, 10-11 a.m., and 2-3, 6-7, 10-11 p.m. The serum level of Prl autoantibodies was measured by ELISA and compared between matched patients with SSc and SLE and controls (n = 42 each). Standard curves of the Prl ELISA were spiked with 10% sera containing high levels of Prl autoantibodies to test interference. RESULTS: Serum levels of Prl measured in the morning (8-10 a.m.) were significantly higher in patients with SSc (17.9 +/- 7.7 ng/ml), compared with controls (9.3 +/- 4.2 ng/ml; p < 0.05). In SSc, 40% of patients had Prl levels > 20 ng/ml, but no correlation was found with Scl-70 or Prl autoantibodies. Younger patients (< 50 years, n = 23/73) showed higher serum levels of Prl than older patients (21.3 +/- 10.3 vs 16.3 +/- 6.2 ng/ml; p < 0.05). The diurnal rhythm of Prl revealed that both a sustained increase over 24 h and some shift occurred in SSc. Peaks of secretion were detected between 6 and 11 a.m., instead of 2-6 a.m. The median levels of TSH over 24 h in patients with SSc ranged within the normal limits. Nevertheless, in SSc, a significant correlation (r = 0.59, p < 0.01) was found between diurnal rhythms of Prl and TSH. The prevalence of Prl autoantibodies in serum was 8% in SSc, 27% in SLE, and < 5% in controls. However, the presence of Prl autoantibodies did not interfere with our assay. CONCLUSION: Our data confirm that mild hyperprolactinemia occurs in a subgroup of patients with SSc, and showed that the elevated serum level of Prl is due to both a sustained increase over 24 h and a shift in the diurnal rhythm. The correlation between diurnal rhythms of Prl and TSH suggests common regulatory mechanisms.     

Effects of oral cyclophosphamide and prednisolone therapy on the endothelial functions and clinical findings in patients with early diffuse systemic sclerosis

OBJECTIVE: The endothelial damage of microvascular structures in systemic sclerosis (SSc; scleroderma) is associated with increased levels of endothelial adhesion molecules and endothelium-associated cytokines, including E-selectin and thrombomodulin. Although there is still no ideal specific pharmacologic therapy for SSc, cyclophosphamide has resulted in clinical improvement in patients with SSc-related active alveolitis. This study was designed to assess the expression of E-selectin and thrombomodulin in patients with early diffuse SSc, and to investigate the effects of oral cyclophosphamide combined with prednisolone therapy on the levels of these endothelium-associated cytokines and on the patients' clinical outcomes. METHODS: Thirteen patients with early diffuse SSc were treated with oral cyclophosphamide (2-2.5 mg/kg/day) and methylprednisolone (30 mg/every other day) for 1 year. The outcomes were determined as clinical (skin score) and laboratory parameters (including the erythrocyte sedimentation rate, complete blood cell count, levels of C-reactive protein, antinuclear antibody, anti-double-stranded DNA, rate of creatinine clearance, and findings on pulmonary function tests, esophageal manometry, and echocardiography). The concentrations of E-selectin and thrombomodulin were measured in the pretreatment and posttreatment serum samples from the SSc patients and from 12 healthy adults as controls. RESULTS: In the patients with early diffuse SSc, pretreatment and posttreatment mean levels of E-selectin were 51 ng/ml (range 34.2-135.5) and 33.4 ng/ml (range 23-62.5), respectively (P = 0.01), and those of thrombomodulin were 82 ng/ml (range 35.8-120.5) and 74.6 ng/ml (range 23.3-91.3), respectively (P = 0.016). Clinical and laboratory parameters (the skin score and measures of pulmonary function [forced vital capacity and diffusing capacity for carbon monoxide]) were also improved (P < 0.05 for each) at the end of the followup period. CONCLUSION: Combination therapy with cylophosphamide plus prednisolone is effective in the treatment of early diffuse SSc. Circulating levels of E-selectin and thrombomodulin not only demonstrate the extent of endothelial injury and/or activation, but also could be a useful marker to monitor the disease activity in SSc.     

Elevated bioactive prolactin levels in systemic lupus erythematosus--association with disease activity.

OBJECTIVE. To assess the possibility that prolactin (PRL) is involved in the pathogenesis of systemic lupus erythematosus (SLE). METHODS. We determined serum PRL levels in 122 serum samples from 78 unselected patients with SLE (73 women, 5 men, age range 16-71 yrs). Disease activity was defined according to Lupus Activity Criteria Count (LACC) and scored by Systemic Lupus Disease Activity Index (SLEDAI). Serum PRL concentrations were determined by immunoradiometric assay (IRMA) and by biological assay (BA) that evaluates Nb2 lymphoma cell proliferation. RESULTS. Hyperprolactinemia (> 20 ng/ml) was found in 21 patients (26.9%) by IRMA and in 31 (39.7%) by BA. A significant correlation between IRMA and BA PRL levels was found (rs 0.46, p < 0.001). According to LACC, SLE was active in 29 patients and inactive in 49. In those with active disease median PRL levels were higher both by IRMA (18.5 ng/ml, range 2.2-51.2 vs 10.6 ng/ml, range 3.9-29.6; p < 0.001) and BA (21.0 ng/ml, range 12.4-84 vs 14.9 ng/ml, range 4.2-46.1; p < 0.001). Hyperprolactinemia was associated with active disease in 13/21 patients (61.9%) by IRMA and in 18/31 (58.1%) by BA (p < 0.01). SLEDAI scores correlated with PRL levels both by IRMA (rs 0.5, p < 0.001) and BA (rs 0.41, p < 0.02). A followup analysis on serum samples from 44 patients seen again after 6-8 mo confirmed the above results. There was no difference in the rate of different clinical manifestations in hyperprolactinemic and normoprolactinemic subjects, apart from the increased prevalence of malar rash and central nervous system manifestations in the patients with hyperprolactinemia (p < 0.03 and p < 0.01, respectively). CONCLUSION: Hyperprolactinemia was frequently detected in patients with SLE by IRMA and by BA and was associated with disease activity. Our findings suggest that PRL may play a role in the pathogenesis of SLE.     

Clinical significance of serum levels of matrix metalloproteinase-13 in patients with systemic sclerosis

OBJECTIVES: To investigate the clinical significance of serum matrix metalloproteinase-13 (MMP-13) levels in patients with systemic sclerosis (SSc). METHODS: Serum MMP-13 levels were determined by using a peptide substrate cleavage assay in 20 patients with diffuse cutaneous SSc (dcSSc), 20 with limited cutaneous SSc (lcSSc) and 10 normal controls. RESULTS: The serum MMP-13 levels in patients with dcSSc or lcSSc were significantly lower than those in normal controls (53.4 +/- 14.1 vs 73.2 +/- 11.5 ng/ml, P < 0.0005; 59.4 +/- 14.8 vs 73.2 +/- 11.5 ng/ml, P < 0.005, respectively), but there was no significant difference in the serum MMP-13 levels between patients with dcSSc and those with lcSSc. Disease duration prior to the diagnosis was significantly shorter in SSc patients with decreased serum MMP-13 levels than in those with normal levels (3.0 +/- 2.2 vs 8.6 +/- 7.6 yr, P < 0.0005). In addition, serum MMP-13 levels were moderately correlated with the duration of the disease (r = 0.451, P < 0.05). Though there was no significant difference in the frequencies of pulmonary fibrosis or reduced %DLco (diffusing capacity of lung for carbon monoxide), the frequency of reduced %VC (vital capacity) was significantly greater in patients with decreased serum MMP-13 levels than in those with normal levels (73 vs 24%, P < 0.05). CONCLUSIONS: Matrix metalloproteinase-13 may be involved in the fibrotic process of SSc, especially in the initiation of fibrosis. The serum MMP-13 levels may serve as a useful marker for the severity of pulmonary fibrosis in patients with SSc.     

Serum resistin levels: a possible correlation with pulmonary vascular involvement in patients with systemic sclerosis

Our latest studies demonstrated the potential role of adipocytokines, including adiponectin, visfatin, retinol binding protein-4, and apelin, in the pathogenesis of systemic sclerosis (SSc). Given that resistin is another member of adipocytokines with pro-inflammatory and pro-angiogenic properties, we measured serum resistin levels by enzyme-linked immunosorbent assay in 52 SSc and 19 control subjects and evaluated their clinical correlation. Since serum resistin levels greatly and inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction [r = ?0.78, p < 0.05 (n = 9)], we evaluated the clinical correlation of serum resistin levels in SSc patients with normal renal function (n = 43). Although serum resistin levels were comparable between diffuse cutaneous SSc (n = 22), limited cutaneous SSc (n = 21), and control subjects (n = 19) [median (25–75 percentiles); 18.7 ng/ml (13.3–48.0), 23.3 ng/ml (12.9–54.1), and 22.9 ng/ml (9.4–36.7), respectively], the prevalence of elevated right ventricular systolic pressure (RVSP) was significantly higher in SSc patients with elevated serum resistin levels than in those with normal levels [67 % (4/6) vs. 16 % (6/37), p < 0.05], and serum resistin levels were significantly increased in SSc patients with elevated RVSP (n = 10) as compared to those with normal RVSP (n = 33) [52.1 ng/ml (20.8–117.5) vs. 18.5 ng/ml (12.2–46.2), p < 0.05]. Thus, serum resistin levels may serve as a useful marker for pulmonary vascular involvement in SSc, suggesting a possible contribution of resistin to the pathogenesis of pulmonary arterial hypertension associated with SSc.     

Clinical significance of surfactant protein D as a serum marker for evaluating pulmonary fibrosis in patients with systemic sclerosis.

OBJECTIVE: To determine the clinical significance of surfactant protein D (SP-D), a useful marker for evaluating various lung diseases, in patients with systemic sclerosis (SSc) and to clarify any clinical significance between SP-D and KL-6, which is known to be correlated with pulmonary fibrosis (PF) in SSc patients. METHODS: We used a specific enzyme-linked immunosorbent assay to measure serum SP-D levels in 83 patients with SSc and 31 healthy control subjects. RESULTS: The serum levels of SP-D were significantly higher in patients with SSc than in healthy controls (mean +/- SD 81.9+/-59.2 versus 34.8+/-13.7 ng/ml). Serum SP-D levels in patients with diffuse cutaneous SSc were significantly higher than those in patients with limited cutaneous SSc (98.8+/-72.1 versus 66.8+/-40.0 ng/ml). Serum SP-D levels in patients with PF were significantly elevated compared with those in patients without PF (99.7+/-64.1 versus 65.3+/-49.4 ng/ml). Moreover, the incidences of decreased percentage diffusing capacity for carbon monoxide and decreased percentage vital capacity were also significantly greater in patients with elevated SP-D levels than in those with normal levels (67% versus 43% and 36% versus 17%, respectively). There was a significant positive correlation between serum levels of SP-D and KL-6. Serum SP-D and KL-6 levels showed almost the same sensitivities and specificities in the diagnosis of PF (68% versus 73% and 70% versus 74%, respectively). These two markers also predicted PF to almost the same degree (31% versus 33%, respectively). CONCLUSION: These results suggest that SP-D, as well as KL-6, may be a useful serum marker for evaluating PF in patients with SSc.     

Serious gastrointestinal pathology found in patients with serum ferritin values ≤ 50 ng/ml

Objective: Our aim was to evaluate the gastrointestinal tract in patients with serum ferritin values ≤ 50 ng/ml for the presence of serious gastrointestinal pathology, including neoplasia and acid peptic disease.
Methods: In this prospective observational study, patients with serum ferritin values ≤ 50 ng/ml who did not have an obvious cause of iron deficiency underwent colonoscopy and/or esophagogastroduodenoscopy.
Results: Between October 1, 1994, and February 29, 1996, 725 of 3015 patients who had serum ferritin determinations were found to have values ≤ 50 ng/ml. To date, 143 patients have been fully evaluated and 77 were found to have serious gastrointestinal pathology including acid peptic disease (  N = 46  ), cancer (  N = 15  ), and large adenomas (  N = 6  ). Colon cancer was discovered in five asymptomatic patients. The prevalences of serious gastrointestinal pathology did not differ between patients with serum ferritin values ≤ 20 ng/ml and those with values between 21–50 ng/ml (  63% vs 48%  ,   p = 0.07  ). However, multivariate analysis showed that the presence of upper or lower gastrointestinal symptoms and serum ferritin value ≤ 20 ng/ml is predictive of finding serious pathology (p = 0.0002 for the whole model), with odds ratios of 3.8 (95% confidence interval of 1.84–7.70) for presence of gastrointestinal symptoms and 2.2 (95% confidence interval of 1.09–4.57) for serum ferritin value ≤ 20 ng/ml.
Conclusions: Endoscopic examination is warranted in patients with serum ferritin values ≤ 50 ng/ml to detect serious gastrointestinal pathology, present in 54% of such patients.     

维生素D缺乏与高血压病患者血清NT pro BNP浓度的关系

目的:研究高血压病患者中维生素D的缺乏与血清N末端脑钠尿肽原（NT-pro-BNP）浓度的关系。方法:选取2009年～2012年住院高血压病患者，根据血清25-羟维生素D［25(OH)D］浓度由高到低将入选患者分为4组:A组:对照组25(OH)D浓度≥30 ng/ml；B组:20 ng/ml<25(OH)D浓度<30 ng/ml；C组:10 ng/ml<25(OH)D浓度<20 ng/ml；D组:25(OH)D浓度≤10 ng/ml，测定血清NT-pro-BNP浓度，并作受试者血清各指标与血清NT-pro-BNP浓度相关性的分析。结果: B组和C组血清NT-pro-BNP浓度较对照组没有显著性差异。D组血清NT-pro-BNP浓度较对照组明显升高，差异有统计学意义（P<0.05），D组血清NT-pro-BNP浓度较C组升高，差异有统计学意义（P<0.05），即随着血清25(OH)D浓度的降低其血清NT pro BNP浓度显著升高。受试者血糖、血钙、总胆固醇、三酰甘油、糖化血红蛋白（HbA1C）、同型半胱氨酸、肌酐、甲状旁腺素与血清NT pro-BNP浓度没有相关性。结论:维生素D的缺乏明显增加高血压病患者发生心力衰竭的风险。     

Serum netrin-1 levels in systemic sclerosis patients with capillary abnormalities

BackgroundSystemic sclerosis (SSc) is a rare, potentially destructive systemic autoimmune disease characterized by organ fibrosis and vasculopathy. Netrin-1 is associated with angiogenesis, inflammation, and apoptosis.Aim of the workTo assess the level of serum netrin-1 in SSc patients with capillary abnormalities and to evaluate its relation to disease manifestations.Patients and methodsThis study investigated the relationship between netrin-1 and fibrosis in 56 SSc patients and 58 matched control. The modified Rodnan skin score (mRss) was used to assess skin thickness. Serum netrin-1 level was quantitatively measured using an enzyme-linked immunosorbent assay.ResultsThe study included 56 patients; 53 females and 3 males (F:M 17.7:1) with a mean age of 48·1 ± 13·6 years and disease duration of 13.01 ± 8·7 years. They were 43 (76.7 %) diffuse and 13 (23.3 %) limited subtypes. The median mRss was 6.58 ± 2.2. Raynaud’s disease was present in 50 % and interstitial lung disease in 57.1 %. The median netrin-1 level was significantly higher in SSc patients (268·8 pg/mL; 82·8-1006·6 pg/mL) than in the controls (108·6 pg/mL;21·02-351·5 pg/mL, p < 0·0001). There was no significant difference in the serum netrin-1 levels in SSc patients with and without Raynaud’s disease (p = 0.55), interstitial lung disease (p = 0.18), anti-Scl70 positive antibodies (p = 0·78), and anti-centromere antibody (p = 0·493). Netrin-1 was significantly related to SSc (OR = 1·02, 95 %CI: 1·01 ? 1·03, p < 0·0001). At a cut-off value 126·3 pg/mL, netrin-1 would diagnose SSc (sensitivity 60·3%, specificity 94·6%, 95 %CI: 0·83 ? 0·95, p < 0·0001).ConclusionSSc patients had significantly high levels of serum netrin-1 with a potential role in the pathophysiology of the disease.     

Bone density in Moroccan women with systemic scleroderma and its relationships with disease-related parameters and vitamin D status

In this case-control study, our first aim was to evaluate the bone mineral density (BMD) in women with systemic sclerosis (SSc) and its correlates. Secondarily, we aimed to evaluate 25-hydroxyvitamin D3 status and its relationships with disease parameters and BMD. Sixty patients with SSc and 60 age-and gender-matched controls were included in the absence of confounding factors that interfere with bone metabolism. Body mass index, menopausal status, familial history of osteoporosis and/or fractures; personal fracture history; exercise activity and laboratory parameters of bone metabolism were assessed in patients and controls. BMD was measured by using a dual-energy X-ray absorptiometry in lumbar spine (L1-L4) and femoral neck. The 25-hydroxyvitamin D3 was measured in a subgroup of 30 patients and in a subgroup of 30 matched controls. Systemic manifestations of SSc, biological inflammatory parameters, functional disability (scleroderma health assessment questionnaire (S-HAQ)) and immunological status of disease were collected in patients' group. The mean age of patients was 49.44?±?13.07?years versus 49.55?±?12.11 in controls. The mean disease duration was 9.63?±?5.9?years. SSc patients had a significantly earlier age and longer duration of menopause than controls (P?=?0.003). Phosphocalcic metabolism parameters were within normal ranges in both groups. BMD was significantly lower in SSc patients than in controls both in lumbar spine (-2.97?±?0.25 in patients vs. 0.46?±?0.11 in controls) and femoral neck (-1.93?±?0.32 in patients vs. -0.81?±?0.69 in controls) (P?相似文献