Subclinical coronary atherosclerosis, detected by computer tomography with coronary calcium score, and the occurrence of major cardiovascular events at 5 years of follow-up in a cohort of patients with systemic sclerosis.

BACKGROUND: Spreading data describe cardiovascular disease (CVD) as a growing cause of hospitalization in systemic sclerosis (SSc) patients. Although interstitial lung disease and pulmonary arterial hypertension (PAH) remain the principal causes of mortality, the presence of CVD has been shown to further increase mortality in SSc patients. Few and contrasting data are available on cardiovascular impairment, particularly of subclinical coronary arteries disease, in SSc patients. The aims of this study were: 1) to determine the demographic, clinical, and cardiovascular differences between the groups of SSc patients with and without subclinical coronary atherosclerosis (SCA) assessed by coronary calcium score; 2) to verify the performance of cardiovascular risk scores in SSc for detection of SCA major cardiovascular events (MCVE); 3) to evaluate the risk factors associated to MCVE in 5 years of follow-up in this study group of patients. METHODS: Sixty-seven SSc patients were enrolled in this study. SCA was assessed using quantification of coronary calcium score by computerized tomography, reported as Agatson. Evaluation of common cardiovascular risk scores, carotid plaques by Doppler ultrasonography, the history of peripheral artery disease (PAD), lipid profiles, and clinical and laboratiristic characteristics of SSc were assessed at baseline visits for each patient. Factors associated with the presence of SCA were assessed by multivariate logistic analysis. A five years prospective study was performed for the evaluation of MCVE occurrence and its possible predictors. RESULTS: The prevalence of SCA was 42% (Agatston scores of 266.04 ± 455.9 units) in our group of SSc patients. Patients with SCA were principally older (p = 0.0001) and had higher rates of CENP-B antibodies (57% vs 26%; p = 0.009), pulmonary arterial hypertension (PAH) (25% vs 3%; p = 0.008), dysphagia (86% vs 61%; p = 0.027), and users of statins (36% vs 8%; p = 0.004), carotid plaque (82% vs 13%; p = 0.0001), PAD (79% vs 18%; p = 0.0001), and metabolic syndrome (25% vs 0%; p = 0.002) than patients without SCA. Metabolic syndrome (OR: 8.2, p = 0.0001), presence of a PAD (OR: 5.98, p = 0.031), and carotid plaque (OR: 5.49, p = 0.010) were the main factors associated with SCA in SSc patients, by multivariate regression analysis. MCVE occurred in 7 patients. By multivariate COX regression analysis unique predictor of MCVE in 5 years of follow-up in our SSc patients was the presence of PAH (HR: 10.33, p = 0.009). Of note, the contemporary presence of PAH and SCA (defined as "not pure" pattern of PAH) was observed in 71% of patients with the occurrence of MCVE CONCLUSION: This study evidenced the high presence of the new "not pure" pattern of PAH, which could worsen the outcome in SSc in a medium-term (5 years) observation period. Furthermore, our data confirmed a higher cardiovascular impairment in SSc due to the presence of both SCA, mainly associated with typical cardiovascular risk factors, and PAH, life-threatening complications of SSc, that is the principal cause of the occurrence of MCVE in our SSc patients. A careful assessment of cardiovascular involvement in SSc and a more aggressive therapeutic strategy for preventing CAD and treating PAH should be highly suggested to reduce MCVE in SSc patients.

Evidence for increase in finger blood flow, evaluated by laser Doppler flowmetry, following iloprost infusion in patients with systemic sclerosis: a week-long observational longitudinal study.

OBJECTIVES: Iloprost plays an important role in the treatment of Raynaud's phenomenon (RP), but has transient vasodilatory effects owing to its very short half-time. We aimed to evaluate short- and medium-term haemodynamic effects of iloprost by measuring dorsal finger microvessel blood flow using laser Doppler flowmetry (LDF), in patients with RP associated with systemic sclerosis (SSc). METHOD: In 24 consecutive SSc patients with RP (disease duration 10.5 ± 1.3 years), LDF with heating probes was used to measure blood flow in four fingers by occlusive and heating tests, at baseline, after 3 consecutive days of iloprost infusion, and at 24 h and 7 days after last iloprost infusion. Nailfold videocapillaroscopy (NVC) patterns of microvascular damage were investigated. Sixteen healthy controls were studied to compare baseline flows. RESULTS: Compared to controls, SSc patients showed significantly impaired axon reflex vasoregulation and nitric oxide responses at baseline (p = 0.001 and p = 0.03, respectively). After iloprost, a prompt but transient significant improvement in endothelial-dependent vasodilation (occlusive test) was seen only in SSc patients with an 'active' NVC pattern (p ≤ 0.05). The iloprost effects vanished within 7 days after the last infusion. No significant differences were found, in the whole study, between patients with and without digital ulcers. CONCLUSIONS: Microcirculatory blood flow increases following 3 days of iloprost infusion but fades shortly after treatment. Although iloprost is effective in reducing the severity of RP in SSc, the most suitable regimen and timing to obtain longer lasting vasodilatory benefits remain to be established.

Intra-articular therapy with tumor necrosis factor-α antagonists: an update.

The aim of the study was to review from the present literature the intra-articular (IA) use of the TNF-blocking drugs. A total of 28 papers about this topic were found through a search in PubMed; the first publication's date was July 2003. These studies include a total of 214 patients affected by 12 different joint diseases that reported a total of 1046 intra-articular therapies carried out in 10 different joint sites. Infliximab and etanercept were the most widely used medications. The safety of this treatment clearly emerges from our analysis, while more difficult was the evaluation of its efficacy. Nevertheless we deduced an ideal patient profile that may better respond to the IA anti-TNF treatment.

Impact of laparoscopy on the management of an unusual case of nonpalpable testis in an adult patient.

BACKGROUND: In the past decade, cryptorchidism has generally been treated in the first 36 months of life using an inguinal approach, in the case of palpable testis, or using laparoscopy, in the case of nonpalpable testis. Nevertheless, before this period some children were managed incorrectly. This case report shows how laparoscopy and the collaboration between pediatric surgeons and urologists may lead to optimal results. CASE REPORT: A 19-year-old male was referred to our unit following routine medical examination for enrollment in the military service with a diagnosis of right cryptorchidism. The clinical history showed the anamnesis of right cryptorchidism diagnosed at birth as a right nonpalpable testis, confirmed at 2 years of age with clinical examination and computer tomography. The patient came to our attention to again undergo a clinical examination, ultrasonography, computed tomography, and magnetic resonance imaging. We found a left, well-positioned testis of 20 ml in volume and an empty right scrotum; all the instrumental examinations were negative. The patient was thus scheduled for a diagnostic laparoscopy. A pediatric surgeon with extensive experience in this pathology performed the procedure. The 10-mm 30 degrees optics introduced through the umbilicus showed a closed right inguinal ring, with no evidence of either vas deferens or inner spermatic vessels at the level of the inguinal region or pelvis. Two more trocars were introduced and a testis of 15 ml in volume was found under the ascending colon 10 cm away from the cecum. An orchiectomy was performed via laparoscopy. CONCLUSION: This case clearly shows that some males with nonpalpable testis may have been treated incorrectly in the prelaparoscopic era and may now have an intraabdominal testis. In addition, our experience shows that intraabdominal testis may sometime be in an unusual location, and a laparoscopic surgeon with experience in this pathology is fundamental to finding the testis. In the case of adults with nonpalpable testis, when echography, computed tomography, and magnetic resonance imaging are not useful, the only effective diagnostic procedure is laparoscopy.

Upregulation of nitric oxide synthase in cultured human keratinocytes after ultraviolet B and bradykinin.

Ultraviolet B (UVB) irradiation of the skin has been reported to upregulate nitric oxide synthase (NOS) activity with enhancement of nitric oxide (NO) formation. Bradykinin, a known stimulator of NO production, is produced in the skin within minutes of UVB irradiation. The combined effect of UVB and bradykinin on NOS was therefore examined in a cultured human keratinocyte (KC) line. Activity was determined in KC homogenates by the recovery of [3H]L-citrulline using labeled L-arginine as the substrate in the presence of mM NADPH. Monoclonal antibodies to specific isoforms of NOS that cross-react with their human counterparts were used to determine the isoform(s) in control, UVB, bradykinin treated and UVB and bradykinin treated KC. Human KC express NOS activity which is lowest at confluence and highest during proliferation. UVB increased NOS activity when a set dose of irradiation was administered from 32.2-48.3 mJ/cm2 but was inhibitory after 64.4 and 80.5 mJ/cm2. Thirty min after 10(-6) M bradykinin, NOS activity nearly doubled followed by return of activity to control levels at 60 min. Activity after UVB and bradykinin was only slightly higher than that observed with bradykinin alone. Immunochemically, an isoform of M(r) 155 kDa was detected in control cells with the antibody for the constitutive brain enzyme, bNOS. Recovery of this isoform increased after UVB treatment as well as after bradykinin which was time dependent. When both stimulants were used, the recovery of the 155 kDa enzyme was markedly enhanced, unlike the enzyme activity findings. These data indicate that the expression of NOS activity under unstimulated conditions in human KC in culture is due to the constitutive NOS found in neuronal tissue, bNOS. The recovery of bNOS increased after UVB and after bradykinin while the combination of both resulted in the synergistic increase in bNOS protein with only a marginal further increase in NOS activity.

Enhanced keratinocyte prostaglandin synthesis after UV injury is due to increased phospholipase activity.

The possibility that increased eicosanoid synthesis in skin after ultraviolet light irradiation is due to enhanced phospholipase activity was examined. [3H]arachidonic acid-labeled human keratinocyte cultures exposed to 30 mJ/cm2 ultraviolet (UV) B were studied 6 h after injury. Bradykinin-stimulated release of [3H]arachidonic acid was increased 1.8-fold over release from control cultures by prior irradiation. In unlabeled cultures, prior irradiation produced a threefold increase in bradykinin-stimulated prostaglandin (PG) E2 synthesis as measured by immunoassay. The relative contribution of increased phospholipase vs. cyclooxygenase activity was therefore examined using stable isotope mass measurements of PGE2. By this method, prior irradiation increased bradykinin-stimulated phospholipase activity 3.5-fold, while no change in total cellular cyclooxygenase activity was observed. The effects of irradiation on phospholipase activity were then assessed in more detail. The activities of phospholipase A2, arachidonoyl-CoA synthetase, and arachidonoyl-CoA lysophosphatide acyltransferase in cell homogenates were determined. No effect of UV exposure on the activity of these enzymes was observed. These results suggest that the increase in prostaglandin synthesis produced after UV irradiation is due to increased phospholipase activity, thus enhancing arachidonate release.