Screening of distress among hospitalized patients in a department of internal medicine.

A psychosomatic approach to the basic screening of distress for patient care in hospitals and other health services is presented. The aims of this study were to verify association between: (1) medical illnesses and distress; (2) patients' needs and distress; (3) type of illness and patients' needs; (4) patients' needs and sense of coherence. One hundred and eighty-nine patients (78 F and 111 M, average age 65 years±8.43) were assessed by self-report questionnaires. We found that higher anxiety and/or depression levels were associated with urogenital (p=0.026), rheumatologic (p=0.006), oncological (p=0.011), neurological (p=0.026) and respiratory (p=0.013) illnesses. Higher distress scoring was associated with rheumatologic illnesses (p=0.024) and illnesses of the liver and digestive system (p=0.037) while a higher severity of distress was associated with oncological illnesses (p=0.011). Depression/anxiety were associated with the need to speak to a psychologist (p=0.050), to a spiritual advisor (p=0.009), to be more reassured by relatives (p=0.017), to feel less abandoned (p=0.036). Only low sense of coherence was associated with the need for greater dialogue with physicians (p=0.012), the need to participate less in treatment decisions (p=0.041), the need to feel less left to one's own devices (p=0.023). Several needs are associated with medical illnesses. In conclusion, these results indicate that early psychological screening could be important to avoid worse or chronic distress.

Ankylosing spondylitis: how diagnostic and therapeutic delay have changed over the last six decades.

OBJECTIVES: Ankylosing spondylitis (AS) is a chronic, progressive, and disabling disease, but the diagnosis is often missed and markedly delayed. An early diagnosis is important to establish a treatment to reduce disability and modify the natural course of disease. The aim of this study was to investigate the diagnostic (DD) and therapeutic (TD) delay according to the decade of diagnosis. The DD and TD correlation with radiological severity score and the new imaging techniques used in diagnosis (magnetic resonance [MRI], computerised tomography, scintigraphy for sacroiliac joints) were also investigated. METHODS: 135 AS patients (45 female and 90 male, 36.5±10.2 years old at diagnosis) with disease onset between 1950 and 2008, were investigated; the time from onset to diagnosis (DD) and treatment (TD), the New York and ASAS criteria fulfilment, the New York sacroiliac radiological score, bamboo spine presence at first visit and the new imaging technique used at diagnosis were recorded and their correlations were analysed. RESULTS: The New York and ASAS criteria were met at the first visit, by 87% and 96%, respectively. The delay from onset of symptoms to diagnosis and treatment was 9±8 and 12±11 years, respectively, but decreased significantly between different decades (p<0.001). The severity of sacroiliitis (mean 2±1; 17/135, 12.5% - IV grade sacroiliitis at diagnosis) and bamboo spine (3.7% at diagnosis) correlated with DD and TD (p<0.001). Sacroiliac MRI use at diagnosis significantly decreased both DD and TD (p>0.001 and p<0.05, respectively). CONCLUSIONS: DD and TD were correlated to radiological severity; they progressively decreased over 6 decades.

Longitudinal ultrasound and clinical follow-up of Baker's cysts injection with steroids in knee osteoarthritis.

This study was conducted to assess ultrasound (US) and clinical changes of Baker's cyst (BC) of patients with knee osteoarthritis (OA) after steroid injection. Patients with knee OA complicated with symptomatic BC (40) were treated with US-guided direct (posterior) aspiration. The injection of 40 mg triamcynolone acetonide was in 20 patients direct into the BC and in other 20 subjects intra-articular (anterior). BC diameters (longitudinal, transverse, and thickness) were measured and followed up with US at baseline, 2, 4, and 8 weeks after injection. Swelling, pain, and range motion were scored at clinical examination with Rauschning and Lindgren classification (RLC, since 0 normal to 3 maximal signs). All US measures of BC and RLC significantly decreased after treatment, in comparison to baseline (p < 0.001) and during the follow-up, did not change through the time (no significant difference between 2, 4, and 8 weeks). At 4 and 8 weeks, diameters measured at US are lower when BC is directly infiltrated in comparison to intra-articular injection (p < 0.01). US steroid direct injection reduces US measures and clinics of BC in knee OA, in particular, when steroid is directly infiltrated into BC.

Evidence for the prevention of enthesitis in HLA-B27/hß(2)m transgenic rats treated with a monoclonal antibody against TNF-α.

Transgenic rats with high expression of HLA-B27 and human ß(2) -microglobulin (B27TR) develop a multisystem inflammatory disease resembling human inflammatory bowel disease (IBD) and spondyloarthropaties (SpA). Tumour necrosis factor α (TNF-α) has a crucial role in sustaining chronic inflammation in the gut and joints. The aim of this work was to evaluate whether TNF-α blockade could prevent or reduce the inflammation of peripheral joints in B27TR. A first group of 9-week-old B27TR received an anti-TNF-α monoclonal antibody (mAb) or an isotypic IgG2a,k up to the age of 18 weeks. An untreated group was monitored up to the age of 18 weeks and then randomly assigned to a 9-week treatment with anti-TNF-α mAb or IgG2a,k. Each rat was monitored for clinical IBD and peripheral joint manifestations. After sacrifice the colon and hind paws were examined for macroscopical and microscopical pathological changes. Early TNF-α blockade prevented, and late treatment improved IBD signs in B27TR. Erythema, oedema, inflammatory infiltrate close to the tendons and enthesis, proliferating chondrocyte-like cells, signs of new endochondral bone ossification and bone erosion were observed in peripheral joints of four out of six IgG2a,k-treated B27TR, both at 18 and 27 weeks. Immunopositivity for phosphorylated Smad1/5/8 indicated that the process of joint remodelling was activated in B27TR. Some entheses showed chondroid nodules. Anti-TNF-α treatment reduced inflammation and preserved the enthesis organization in most animals. Occasional and transient erythema and oedema were still present in three of six of the late anti-TNF-α-treated animals. Smad1/5/8 signalling was not inhibited by late anti-TNF-α treatment. In B27TR, articular involvement follows IBD onset and develops at entheses. Early TNF-α blockade prevents the onset of IBD and consequently the development of enthesitis in peripheral joints in the B27TR model of human SpA.

Anti-hnRNP and other autoantibodies in systemic sclerosis with joint involvement.

OBJECTIVES: To investigate joint involvement in SSc and its relationship with autoantibody to the hnRNP and to anti-cyclic citrullinated peptide (anti-CCP). METHODS: Sera from 55 SSc patients were investigated. Joint involvement was determined by clinical, radiological and ultrasonographical evaluation. Anti-hnRNP proteins A1 and A2 (anti-hnRNP-A1/A2) antibodies were determined by immunoblotting. Anti-CCP, ACA, anti-topo I (ATA), Sm, U1-RNP, ribosomal RNP, Ro/SSA, La/SSB autoantibody and RF were determined. RESULTS: Six patients were positive for anti-hnRNP-A2 autoantibody and two were anti-A1 positive. Eight patients had joint erosions: seven of the eight patients positive for anti-hnRNP-A2 or A1 presented articular involvement (P < 0.04) and five of the eight erosive patients were positive for either of the two autoantibodies (P < 0.02). Of the four patients positive for anti-CCP, none had anti-hnRNP but three had erosive aspects. ATAs were found in 10 patients, six of which were also positive for anti-hnRNP (P < 0.05). RF was positive in 16 patients and in seven among those with articular involvement (P < 0.04). RF was significantly associated with anti-hnRNP in patients with erosive arthritis (P < 0.02), but not with the presence of anti-hnRNP alone. Epitope mapping of the three strongest anti-hnRNP-A2-positive sera recognized the same major epitope as patients with RA. SSc patients have higher incidence of erosions and anti-hnRNP-A2/A1 positivity. RF test and anti-hnRNP had a statistically significant diagnostic value for articular involvement. CONCLUSIONS: These parameters might suggest that autoantibody to both hnRNP antigens might become a non-specific but useful marker for joint involvement in SSc patients and identify SSc patients prone to develop joint damage.

TNFalpha blockade prevents the development of inflammatory bowel disease in HLA-B27 transgenic rats.

Abstract Rats transgenic for HLA-B27 and human beta2microglobulin (B27TR) develop a multi-systemic disease resembling inflammatory bowel disease (IBD) and spondyloarthritis. TNFalpha has a crucial role in chronic inflammation. Our objective was to evaluate the effect of anti-TNFalpha treatment on spontaneous IBD in B27TR. Nine-week-old B27TR received monoclonal anti-TNFalpha or an isotypic IgG2a,k up to age of 18 weeks. A second group was monitored up to 18 weeks and then randomly assigned to anti-TNFalpha or IgG2 a,k treatment. Each rat was monitored for clinical IBD manifestations. After sacrifice, the colon was examined for pathological changes. TNFalpha receptors (TNF-R1, TNF-R2), Fas/Fas-L expression and apoptosis were evaluated. IgG2a,k-treated and untreated B27TR presented signs of IBD at 11 weeks, whereas in anti-TNFalpha-treated B27TR no IBD signs were detected. In the late treatment, IBD signs improved after 1 week. Histopathological analysis of IgG2a,k-treated B27TR colon showed inflammatory signs that were widely prevented by early anti-TNFalpha treatment. Late treatment did not significantly reduce inflammation. TNF-R1 was weakly expressed in intestinal epithelial cells of IgG2a,k-treated B27TR, while it was comparable to controls in anti-TNFalpha-treated animals. TNF-R2 immunopositivity was strongly evident in IgG2a,k-treated B27TR, whereas was absent in anti-TNFalpha-treated rats. RT-PCR confirmed these results. IgG2a,k-treated B27TR showed, at 18 weeks, few Fas-positive cells and an increase of Fas-L-positive cells. At 27 weeks, Fas-/Fas-L-positive cell number was significantly low. Anti-TNFalpha treatment increased Fas-L expression, whereas Fas increased only with the early treatment. TNFalpha blockade is effective in preventing inflammation in early phase of IBD, maintaining the homeostatic balance of apoptosis.

Exercise Doppler echocardiography identifies preclinic asymptomatic pulmonary hypertension in systemic sclerosis.

In systemic sclerosis (SSc), the involvement of the interstitium or vascular system of the lung may lead to pulmonary arterial hypertension (PAH). PAH is often asymptomatic or oligosymptomatic in early SSc and, when it becomes symptomatic, pulmonary vascular system is already damaged. Exercise echocardiography (ex-echo), measuring pulmonary artery pressure (PAP) during exercise and allowing to differentiate physiologic from altered PAP responses, may identify subclinical PAH. Our aims were (a) to evaluate by ex-echo the change of PAP in patients with SSc without lung involvement; and (b) to correlate PAP during exercise (ex-PAP) values to clinical and biohumoral parameters of PAH. Twenty-seven patients with limited SSc (ISSc) without interstitial lung involvement were studied. Patients underwent rest and exercise two-dimensional and Doppler echocardiography by supine cycloergometer. Systolic PAP was calculated using the maximum systolic velocity of the tricuspid regurgitant jet at rest and during exercise values of systolic PAP exceeding 40 mmHg at ex-echo were considered as abnormal, and biohumoral markers potentially related to PAH were assessed. Eighteen of 27 SSc patients presented an ex-PAP > 40 mmHg, while in 9 of 27 patients ex-PAP values remained < 40 mmHg (48.8 +/- 4.5 mmHg versus 36.2 +/- 3.1 mmHg; P < 0.001). Other echocardiographic and ergometric parameters, clinical tests, and biohumoral markers were not different in the two groups. Ex-PAP significantly correlated with D-dimer (P = 0.0125; r2 = 0.2029). Ex-echo identifies a cluster of SSc patients with subclinical PAH that may develop PAH. This group should be followed up and may be considered for specific therapies to prevent disease evolution.

Reduced circulating levels of angiotensin-(1--7) in systemic sclerosis: a new pathway in the dysregulation of endothelial-dependent vascular tone control.

OBJECTIVE: Systemic sclerosis (SSc) impairs endothelium-dependent vasodilatation. Among angiotensin I (Ang I)-derived compounds, vasoconstrictor angiotensin II (Ang II) and vasodilator angiotensin-(1-7) (Ang-(1-7)), cleaved from ACE and neutral endopeptidase (NEP) 24.11, respectively, play an important role in vascular tone regulation. Ang-(1-7) may act independently or by activating other vasodilating molecules, such as nitric oxide (NO) or prostaglandin I2 (PGI2). Our aim was to assess, in patients with SSc, circulating levels of Ang I, Ang II and Ang-(1-7), with their metabolising enzymes ACE and NEP, and levels of NO and PGI2, and to correlate them to the main characteristics of SSc. METHODS: Levels of Ang I, Ang II, Ang-(1-7), NEP, ACE, NO and PGI2 were measured in 32 patients with SSc, who were also assessed for humoral and clinical characteristics, and 55 controls. RESULTS: Plasma Ang I, Ang II and Ang-(1-7) levels were lower in patients with SSc than in controls (p<0.001in all cases). When Ang II and Ang-(1-7) levels were expressed as a function of the available Ang I, lower Ang-(1-7) levels in patients with SSc than in controls were confirmed (p<0.001), while no difference was found for Ang II levels. In patients with SSc, the Ang II/Ang-(1-7) ratio indicated a prevalence of Ang II over Ang-(1-7), while in controls Ang-(1-7) was prevalent (p<0.001). Levels of ACE, NEP, NO and PGI2 were lower in patients with SSc than in controls (p<0.05 in all cases). CONCLUSION: In patients with SSc, prevalence of the vasoconstricting Ang II over the vasodilator Ang-(1-7) suggests a dysfunction of the angiotensin-derived cascade that may contribute to dysregulation of vascular tone.

Melatonin is a safe and effective treatment for chronic pulmonary and extrapulmonary sarcoidosis.

Chronic sarcoidosis (CS) is often unresponsive to usual treatments. Melatonin, an immunoregulatory drug, was employed in CS patients in whom usual treatments were ineffective or induced severe side effects. Melatonin was given for 2 yr (20 mg/day in the first year, 10 mg/day in the second year) to 18 CS patients. Pulmonary function tests, chest X rays, pulmonary computed tomography, Ga(67) scintigraphy and angiotensin-converting enzyme (ACE) were assayed at baseline and in the follow-up. Normalization of ACE, improvement of pulmonary parameters and resolution of skin involvement were found in the patients given melatonin. After 24 months of melatonin therapy, hylar adenopathy completely resolved in eight patients and parenchymal lesions were markedly improved in all patients; in the five patients with reduced diffusion capacity of the lung for carbon monoxide, the values normalized after 6 months of therapy and remained stable until month 24. After 24 months, Ga(67) pulmonary and extra-pulmonary uptake was totally normalized in seven patients and, at month 12 months, ACE was normalized in six patients in which the values were high at the baseline. Skin lesions, present in three patients, completely disappeared at month 24 months. No side effects were experienced and no disease relapse was observed during melatonin treatment. Melatonin may be an effective and safe therapy for CS when other treatments fail or cause side effects.

Estrogens and neuropeptides in Raynaud's phenomenon.

Raynaud's phenomenon (RP) is characterized by ischemia and reperfusion of the extremities. Vasomotor instability is due to a microcirculatory disturbance that may be linked to different events involving the endothelium or peripheral nerve terminals. Endothelium and nerve endings "sense" the modifications of the microenvironment and both of them release factors that contribute to find a balance between vasolidation and vasoconstriction. Moreover, estrogens may contribute to control vascular tone regulating finger skin circulation. A loss of neuropeptides has been shown in secondary RP where supplementation with factors derived from nerve endings has been demonstrated to induce a potent vasolidation. Estrogen administration improved endothelial dysfunction in secondary RP. Neuropeptides and estrogens thus share the endothelial-dependent pathway, usually mediated by nitric oxide, in inducing vasolidation. The network directed by the endothelium is in reality controlled by a neuro-hormonal axis composed by neuropeptides and estrogens. This delicate balance keeps the vascular tone, and its dysfunction may lead to a dysregulation of vascular tone, manifest in clinics as a primary or secondary RP.

Neprilysin levels in plasma and synovial fluid of juvenile idiopathic arthritis patients.

OBJECTIVE: Neprilysin (neutral endopeptidase, 3:4:24:11, CD10) (NEP) is a Zn metallopeptidase linked to controlling inflammation through the degradation of neuropeptides involved in neurogenic inflammation of chronic rheumatic diseases. The aim of our study was to evaluate circulating activity and cellular expression of NEP in the plasma of 58 children with juvenile idiopathic arthritis (JIA) and 52 controls. In 20 subjects requiring local steroid injection, NEP was measured in synovial fluid. METHODS: Plasma and synovial NEP were evaluated using a fluorimetric technique. Neprilysin, expressed as the antigen CD10, was determined on circulating and synovial fluid cells as mean fluorescence intensity (MFI) and as percentage of positive cells by two-color immunofluorescence. RESULTS: Circulating NEP levels were lower in JIA patients than in controls (42.0+/-16.6 vs 76.5+/-24 pmol/ml per min, P<0.001), while synovial fluid NEP values were higher than circulating levels (241.4+/-86.2 vs 40+/-15.3 pmol/ml per min, P<0.001). In monocytes, the percentage of CD10-positive circulating cells and the MFI in JIA were lower than in controls (11.6+/-5.2% vs 41.4+/-13%, P<0.001 and 18.1+/-7.5 vs 31.2+/-5.4, P<0.05, respectively). On synovial monocytes, the percentage of CD10-positive cells and the MFI were higher than on circulating monocytes (35.2+/-14.6% vs 9.1+/-2.4%, P<0.001 and 66.4+/-5.4 vs 22.8+/-14.7, P<0.001, respectively). CONCLUSIONS: The downregulation of CD10 expression in monocytes and the reduction in NEP activity may be linked to the enzyme's role in the control of peptides involved in the inflammation. The increased levels of NEP, MFI, and CD10-positive monocytes in synovial fluid, even though in plasma, might reflect a reactive effort to control synovial proliferation.

Health-related quality of life in systemic sclerosis as measured by the Short Form 36: relationship with clinical and biologic markers.

OBJECTIVE: To evaluate health-related quality of life (HRQOL) in patients with systemic sclerosis (SSc) using the Short Form 36 (SF-36) and to correlate SF-36 scores with clinical and biologic markers. METHODS: The SF-36 was administered to 24 controls and 24 SSc patients. SSc patients also were evaluated for subset (limited SSc [lSSc] and diffuse SSc [dSSc]), age, disease duration, angiotensin-converting enzyme (ACE) levels, autoantibodies, and skin and internal organ involvement. RESULTS: The physical summary score (PSS) was lower in SSc patients than in controls (P < 0.05), whereas the mental summary score (MSS) was higher in dSSc than in lSSc patients (P < 0.05). Five of 8 single SF-36 domain scores were lower in SSc patients than in controls (P < 0.05). Vitality was higher in dSSc than in controls (P < 0.001). In SSc, elder age correlated with lower PSS; low ACE levels and high skin score correlated with higher general mental health and role limitations due to physical problems, respectively (P < 0.05). Patients with heart involvement had higher scores in general health perceptions (P < 0.05). CONCLUSION: The SF-36 shows that HRQOL is impaired in patients with SSc. Higher scores in MSS and vitality in patients with dSSc and correlations of high SF-36 scores with specific organ involvement suggest that SSc patients with severe disease are more able to cope with HRQOL modification.

Pupillocynetic activity of substance P in systemic sclerosis.

OBJECTIVE: In systemic sclerosis (SSc), dysfunctions of peripheral nervous system (PNS) have been observed. Substance P (SP) instillation in human eye induces a cholinergic-independent pupil myosis. Pupil basal diameters (PBD) and pupil responsiveness to SP, expressed as area under the curve (AUC), were studied by pupillometry to assess SP-ergic fiber state and function in SSc. METHODS: Forty SSc patients [24 with limited (lSSc), 16 with diffuse (dSSc) disease] and 40 controls underwent pupillometric evaluation. After evaluation of PBD, SP 10-3 M was instilled in one eye and placebo in the contralateral eye. Antinuclear (ANA), anticentromere (ACA), and anti-Scl-70 autoantibodies were correlated with PBD and AUC. RESULTS: PBD was significantly lower in SSc patients versus controls (p < 0.001). PBD was minor in lSSc versus both dSSc and controls (p < 0.05), but no difference was found between dSSc and controls. In SSc, SP 10-3 M induced greater myosis compared to controls (p < 0.001). SP 10-3 M-induced myosis was higher in lSSc versus both dSSc and controls (p < 0.05). ACA significantly correlated with decreased values of PBD and AUC (p < 0.001). CONCLUSION: Our results show that PBD is reduced in patients with SSc and that SP induces a more intense myosis in SSc than controls. Moreover, in lSSc PBD is lower and SP increases the myosis in lSSc compared to dSSc and controls. This suggests a peculiar dysfunction of PNS in patients with the limited subset of SSc.

Current Treatment Options in Raynaud's Phenomenon.

The treatment of Raynaud's phenomenon (RP) strictly depends on the severity of symptoms and on the presence of an underlying systemic disease. For this reason, any patient with RP should be carefully assessed for signs and symptoms that may herald an underlying disease. Primary RP can usually be managed with conservative nonpharmacologic lifestyle modifications (eg, avoidance of cold temperatures, tobacco, caffeine, and any drug interfering with vascular tone) and pharmacologic treatment added only if attacks are poorly controlled. Vasodilating drugs (eg, calcium channel blockers, angiotensin II receptor antagonists, topical nitrates, and prostanoids) are still the mainstay of medical therapy for RP. Anecdotal reports with different kinds of therapies appear regularly but always need evidence-based confirmation. In particular, antioxidant agents may be useful in limiting the progressive endothelial damage. Novel therapeutic tools interfering either with primary or secondary pathogenetic processes (ie, endothelial and peripheral nervous system dysfunction and smooth muscle cell hypertrophy) are awaited.

Effect of N-acetyl-L-cysteine on peroxynitrite and superoxide anion production of lung alveolar macrophages in systemic sclerosis.

Lung macrophages may play a relevant role in oxidative processes producing both superoxide anion (O(2)(-)) and NO. In this view, an antioxidant therapy can be useful in the treatment of systemic sclerosis (SSc) patients. N-Acetylcysteine (NAC) is able to expand natural antioxidant defenses by increasing intracellular gluthatione concentration and it has been proposed as an antioxidant therapy in respiratory distress syndromes. The aim of our study was to determine whether lung macrophages obtained from SSc patient bronchoalveolar lavage (BAL) express the inducible form of nitric oxide synthase (iNOS) and whether NAC can reduce the peroxynitrite (ONOO(-)) and O(2)(-) production of these cells. Alveolar macrophages were isolated from BAL of 32 patients and used for the immunocytochemical determination of iNOS, and the production of ONOO(-) and O(2)(-) was measured by fluorimetric or spectrophotometric methods, respectively. Lung macrophages obtained from SSc patients expressed a higher level of iNOS compared to healthy subject cells. NAC preincubation (5 x 10(-5)M, 24h) significantly reduced (-21%) the ONOO(-) production in formyl Met-Leu-Phe (fMLP)-activated cells and slightly reduced it under resting conditions, whereas NAC preincubation was unable to modify the release of O(2)(-) both in basal condition and in fMLP-stimulated cells. We conclude that since SSc lung macrophages express high levels of iNOS and produce a significant quantity of ONOO(-), NAC administration reduces ONOO(-) production and can be an useful treatment to alleviate SSc symptoms.