[Light wellbeing in hospital: research, development and indications]. / Benessere luminoso in ospedale: ricerca, sviluppo e indicazioni di riferimento.

Aim of the research is to form design indicators to guarantee light comfort in hospital environments for inpatients as well for workers. The research is articulated in different phases: drawing up, elaboration and distribution of a questionnaire to study indoor natural and artificial lighting, and effects on human being; architectural and lighting analyses of the investigated hospitals; elaboration -through graphics- of the questionnaire answers; drawing up of design indications for visual comfort in hospitals. These indications relates natural lighting, artificial lighting, indoor spaces and human being.

Central nervous system involvement in HCV-related mixed cryoglobulinemia.

An involvement of the peripheral nervous system is frequent in patients with HCV-related mixed cryoglobulinemia (HCV-MC), whereas central nervous system (CNS) impairment has been rarely reported. To investigate the possible CNS involvement in MC, we evaluated 18 patients by neurophysiological, neuroradiological and neuropsychological methods. Three patients (16.7%) had clinically evident neurological central signs, ten (55.5%) complained of mild symptoms, possibly indicative of CNS impairment, and five (27.8%) did not have any CNS symptom. Evoked potentials (EPs) were abnormal in 83% of the cases (SSEPs in 72%, VEPs in 44%, MEPs in 39% and BAERs in 22%). Brain magnetic resonance imaging (MRI) showed abnormal findings in 83% (small T2-weighted hyperintense lesions in 72%, focal or diffuse atrophy in 50%). Cognitive impairment was detected in 22% of the patients. A mild or subclinical CNS involvement is frequent in MC patients. Neuropsychological, neurophysiological and neuroradiological examination are useful to detect CNS involvement also in asymptomatic subjects.

Hormone replacement therapy may prevent the development of isolated pulmonary hypertension in patients with systemic sclerosis and limited cutaneous involvement.

BACKGROUND: Isolated pulmonary hypertension (iPHT) is a near-fatal consequence of systemic sclerosis (SSc); in female patients, the risk of its development is increased during the post-menopausal period, when the protective effects of oestrogens on the endothelium decrease. In many animal and human models, hormone replacement therapy (HRT) and oestrogen administration proved efficacious in counteracting many mechanisms that might be implicated in the pathogenesis of iPHT. Accordingly, it has been hypothesized that HRT might help to prevent the development of iPHT. METHODS: A retrospective cohort study was conducted on 61 SSc patients with the limited cutaneous form of the disease and no sign of pulmonary hypertension on echocardiogram (pulmonary artery pressure, PAP > 35 mmHg) at the time of menopause. All the patients had to be stably treated with calcium-channel blockers and not to have risk factors for secondary PHT throughout the duration of the observational period. RESULTS: Twenty patients (32.8%) received HRT for a mean of 6.7 +/- 3.7 years. None of these patients developed iPHT after a mean of 7.2 +/- 3.5 years from menopause, whereas eight out of 41 patients not receiving HRT (19.5%) developed iPHT after a similar time period (7.5 +/- 3.9 years, p = 0.032). These rates were not explained by differences between the two groups with respect to autoantibodies, age, age at onset of SSc, diffusing capacity of the lung for carbon monoxide (DLCO) at menopause, or duration of therapy with calcium-channel blockers. CONCLUSION: HRT administration may be effective in SSc post-menopausal women, preventing the development of iPHT.

Clinical and serological associations of ribosomal P autoantibodies in systemic lupus erythematosus: prospective evaluation in a large cohort of Italian patients.

OBJECTIVE: To verify the association of ribosomal anti-P antibodies (anti-P), as detected by a sensitive ELISA, with serological findings and clinical manifestations, including neuropsychiatric involvement evaluated according to the American College of Rheumatology (ACR) nomenclature, in a large cohort of patients with systemic lupus erythematosus (SLE). METHODS: Anti-P were evaluated in the serum of 149 consecutive Italian SLE patients by an ELISA using a multiple antigen peptide carrying four copies of a common P0, P1 and P2 epitope. A complete laboratory evaluation and clinical examination were performed in each patient. In addition, all patients underwent an accurate neuropsychiatric and neuropsychological assessment performed by trained specialists according to the 1999 ACR suggestions. RESULTS: Serum anti-P were detected in 18/149 patients (12.1%). The anti-P prevalence was similar (11.7%) when the analysis was performed in a larger series of sera including 82 additional SLE patients, who were not included in the clinical study. The age of anti-P-positive patients at disease onset was less than 33 yr and, in comparison with the anti-P-negative patients, these patients showed more active disease activity and a higher prevalence of photosensitivity and malar and discoid rash. A strong association between IgG anticardiolipin antibodies and anti-P was also found. However, anti-P were associated with neither neuropsychiatric syndromes nor cognitive impairment. CONCLUSION: This study does not seem to confirm the described association of anti-P with SLE neuropsychiatric manifestations. However, it supports the anti-P association with different skin manifestations as well as the presence of anticardiolipin in a subset of patients with SLE characterized by early disease onset.

Ventilation-perfusion lung scan for the detection of pulmonary involvement in Takayasu's arteritis.

The aim of study was to analyse ventilation and perfusion (V/Q) lung scan findings in a series of Italian patients with Takayasu's arteritis. Eighteen consecutive patients underwent V/Q lung planar scintigraphy and single-photon emission tomography (SPET). Before perfusion scan acquisition was started, a first-pass study with (99m)Tc-macroaggregates of albumin was performed to assess the right ventricular ejection fraction (RVEF). All patients had normal chest X-rays and were symptom free at the time of the investigation. They also underwent echocardiography to evaluate pulmonary artery pressure and in 13 patients respiratory function tests were performed. In four patients, perfusion lung scan was repeated after 1 year. In 10/18 patients (55.5%), 43 unmatched lobar, segmental or subsegmental perfusion defects were found on planar images; ventilation scintigraphy was normal in all cases. On SPET images, 55 defects were found; no defects were found with SPET in the remaining patients who had normal planar images. All patients had normal RVEF and 5/13 patients had mild restrictive-obstructive lung disease. The pulmonary artery pressure was increased in two patients with perfusion defects. In the four patients who had repeat scintigraphy, all defects remained unchanged. The prevalence of lung perfusion abnormalities observed in Italian patients with Takayasu's arteritis is within the range of values reported in other countries, and V/Q planar scintigraphy is sufficient for the screening of patients.

Effects of long-term cyclic iloprost therapy in systemic sclerosis with Raynaud's phenomenon. A randomized, controlled study.

OBJECTIVE: Iloprost is a stable prostacyclin analogue which has been shown to be effective in the short-term symptomatic treatment of Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc). The aim of this study was to evaluate the effects of long-term cyclic therapy with iloprost in comparison with nifedipine on the skin score, pulmonary function and Raynaud's severity score in patients with SSc and RP. METHODS: We conducted a 12-month prospective, randomised, parallel-group, blind-observer trial to compare the effects of intravenously infused iloprost (2 ng/kg/min on 5 consecutive days over a period of 8 hours/day and subsequently for 8 hours on one day every 6 weeks) with those of conventional vasodilating therapy with nifedipine (40 mg/day for os) in 46 patients with SSc and RP. RESULTS: At 12 months, iloprost but not nifedipine reduced the skin score (iloprost: from 13.26 +/- 2.05 to 9.26 +/- 1.32, p = 0.002; nifedipine: from 10.83 +/- 2.09 to 12.17 +/- 3.02, p = n.s.; iloprost vs nifedipine: p = 0.016) and the RP severity score (iloprost: from 2.17 +/- 0.2 to 1.22 +/- 0.13, p = 0.02 vs baseline; nifedipine: from 2.08 +/- 0.34 to 1.33 +/- 0.22, p = n.s.). Carbon monoxide diffusing capacity (DLCO), expressed as % of the predicted normal value, worsened significantly in the nifedipine group (from 69.6 +/- 7.4% to 61.5 +/- 6.5%, p = 0.044) and remained stable in patients treated with iloprost (from 53.2 +/- 4.8 to 56.0 +/- 4.6%, iloprost vs nifedipine: p = 0.026). CONCLUSION: In SSc patients, cyclic intravenous iloprost infusion is able to control vasospastic disease. Our results suggest that it might also act as a disease-modifying agent, as it seems to improve the course of the disease. Further studies principally focused on organ involvement and the natural history of the disease are needed to confirm our results.

Non-invasive assessment of pulmonary artery involvement in Takayasu's arteritis.

OBJECTIVE: To evaluate pulmonary involvement in Italian patients with Takayasu's arteritis (TA). METHODS: A prospective analysis of 15 Italian patients with TA was carried out, including evaluation by perfusion and ventilation lung scintigraphy (planar and tomographic), standard chest X-ray, spirography and color-doppler echocardiography. All the patients were free of respiratory symptoms when examined. RESULTS: In all patients standard chest X-rays and ventilation scintigraphies were normal. 9/15 patients showed unmatched segmental perfusion defects (41 by planar evaluation vs. 48 by SPET). The number of defects was greater in the right lung than in the left (26 vs 18), with a higher frequency of moderate or large defects. Thirteen patients underwent spirography, which proved to be abnormal in 5 cases. Two of these patients were also positive on scintigraphy. No patient showed alterations attributable to TA on color-doppler echocardiography, except for 3 patients with mild to moderate aortic valve regurgitation. CONCLUSIONS: Our results show that vascular pulmonary involvement is frequent in TA (60% of cases) even in the absence of clinical signs. The planar image, simpler than the SPET to acquire, was sufficient to make an accurate diagnosis. Italian patients seem to show a pattern of extrapulmonary and pulmonary vascular involvement very similar to that reported in Japanese subjects, and different from that observed in other ethnic groups.

Central nervous system involvement in systemic lupus erythematosus patients without overt neuropsychiatric manifestations.

OBJECTIVE: To verify whether features of CNS involvement can be detected in SLE patients without overt neuropsychiatric manifestations. METHODS: 114 SLE patients who had never received a diagnosis of neuropsychiatric lupus (never-NPSLE) were studied and compared to 65 SLE patients with known neuropsychiatric involvement (NPSLE). The study relied on evaluation of neurocognitive functions by means of a battery of neuropsychological tests, on psychiatric and neuropsychological assessments and on neuroimaging studies (computed tomography, magnetic resonance, single photon emission computed tomography (SPECT)). RESULTS: Clinical features, including disease duration/activity and pharmacological therapy, of never-NPSLE and NPSLE patients were similar. Short-term and long-term memory, visuo-spatial and verbal information processing were similarly compromised in never-NPSLE and in NPSLE patients; only attention was significantly more compromised in NPSLE patients. Psychiatric morbidity was higher than expected in never-NPSLE patients, although less than in the control neuropsychiatric group. Ischemic lesions, multiple small high intensity lesions and cortical atrophy, detected by CT and MR scans, as well as abnormal SPECT were also frequently detected in never-NPSLE patients. Interestingly, left parietal and occipital area hypoperfusion by SPECT was significantly more frequent in the patients with impaired visuo-spatial intelligence and short-term memory. CONCLUSIONS: Most abnormalities detected by available diagnostic tools and characteristics of neuropsychiatric SLE are also present in non-symptomatic patients. They may derive from an unexpected widespread involvement of the CNS and are not per se sufficient, in the absence of clinical manifestations, for a diagnosis of neuropsychiatric SLE.

Hepatitis C virus genotypes and clinical features in hepatitis C virus-related mixed cryoglobulinemia.

Mixed cryoglobulinemia is a systemic disease, almost always associated with hepatitis C virus infection and characterized by purpura and cutaneous vasculitis, asthenia, arthralgias, and often renal and neurological involvement. No significant differences have been described to date in mixed cryoglobulinemia patients with type 1, 2, or 3 hepatitis C virus infection with respect to symptoms, while a higher prevalence of genotype 2a has been reported in patients without clinical and biochemical signs of liver disease or with serum autoantibodies. We examined 33 hepatitis C virus-positive patients with mixed cryoglobulinemia to assess if any clinical or serological feature is related to infection with different genotypes. All subjects underwent viral genotype determination by means of a single-step polymerase chain reaction. Thirteen patients (39%) were infected with hepatitis C virus type 1b, 17 (52%) with type 2a or 2a/c, and 3 (9%) with type 3. There was a significant difference in the frequency of peripheral nervous system involvement: paresthesias or other symptoms of peripheral neuropathy were less frequent in patients with 2a or 2a/c infection (29%) than in patients with type 1b or type 3 infection (88%, P = 0.003). Only patients with hepatitis C virus type 2 had urticaria or cutaneous ulcers. These patients also had a lower frequency of arthralgias, lower cryocrit values (P = 0.02), and lower serum levels of alanine-aminotransferase and gamma-glutamyl-transpeptidase (P < 0.04) than patients with type 1 and type 3 infection. The prevalence of antinuclear antibody positivity was similar in the three groups.

Central nervous system involvement in patients with HCV-related cryoglobulinemia.

Central nervous system involvement was rarely described in patients with mixed cryoglobulinemia (MC). Most cases were reported before 1991, so these patients were not tested for hepatitis C virus (HCV) infection. However, two cases of cerebral ischemia in patients with HCV-related MC were recently reported. We describe three patients with chronic HCV and cryoglobulinemia, who complained of mild neurologic symptoms (dizziness, equilibrium impairment, monolateral hyposthenia, and defective sensitivity) which can be ascribed to central nervous system involvement. In all of these patients, brain magnetic resonance imaging showed multiple small hyperintensities compatible with ischemic lesions.

Case report: successful treatment with cimetidine and zinc sulphate in chronic mucocutaneous candidiasis.

The authors evaluated the clinical efficacy of a treatment with cimetidine and zinc sulphate in a patient with chronic mucocutaneous candidiasis. Cimetidine was given at a dose of 400 mg three times daily; zinc sulphate at a dose of 200 mg daily, then adjusted to maintain blood zinc levels at the upper normal range. This treatment lasted 16 months. An impressive and significant reduction of the infectious events and an increased CD4 (helper/inducer) cell counts were observed. The authors conclude that this combined immunopotentiating treatment is safe and inexpensive to treat immunodeficiency disorders.

Comparison of different methods for the detection of autoantibodies in autoimmune diseases.

Different immunological techniques were compared for their sensitivity in detecting some important autoantibodies in the sera of patients with rheumatic diseases. Sera of patients with systemic lupus erythematosus were screened for anti-dsDNA, Sm, and RNP autoantibodies by Crithidia luciliae assay, Farr assay, enzyme immunoassay, and immunoblotting. Sera of patients with Sjögren's syndrome were screened for anti-SSA and anti-SSB antibodies by enzyme immunoassay, counter immunoelectrophoresis, and immunoblotting and sera of patients with scleroderma for SCL-70 autoantibodies by enzyme immunoassay counter immunoelectrophoresis, and immunofluorescence on Hep-2 cells. Enzyme immunoassay and counter immunoelectrophoresis gave the most positive results and the best agreement compared with the other techniques. Immunofluorescence gave few positive results for each antibody evaluated. Immunoblotting gave intermediate results for all autoantibodies except anti-SSA, where the prevalence was low. There was no relationship between levels of dsDNA, Sm, and RNP antibodies and disease activity score in systemic lupus erythematosus patients.

The clinical significance of autoantibodies to soluble cellular antigens in systemic lupus erythematosus.

The relationships between autoantibodies to soluble cellular antigens and clinical features in systemic lupus erythematosus (SLE) were investigated in a large clinical-serological study. The absence of these precipitins in serum was associated with a low prevalence of vasculitis and membranous nephropathy (MGN). Other significant findings were the associations between nRNP antibody and Raynaud's phenomenon and MGN, SSB antibody and sicca complex, PCNA antibody and a young age at onset, and Bu antibody and an old age at onset. However, the most impressive findings were in DA1-positive patients which showed a unique prevalence of photosensitive skin lesions, lymphoadenopathy and hepatosplenomegaly. The present study confirms the usefulness of antibodies to soluble cellular antigens in the classification of patients with SLE.

Relationship between antibodies to dsDNA and to soluble cellular antigens and histologically defined glomerulonephritis in patients with SLE.

To better define the relationships between circulating autoantibodies and renal involvement in systemic lupus erythematosus (SLE), antibodies to both dsDNA and soluble cellular antigens were detected in sera from a large series of SLE patients. Significantly higher dsDNA binding activities and lower complement levels at onset were found in patients with renal disease; however, this was uniquely due to subjects with diffuse or focal proliferative glomerulonephritis. Patients with membranous nephropathy (MGN) showed very low dsDNA binding activities (6/9 of them being negative for dsDNA antibodies) and normal mean C3 and C4 levels. A comparison between patients with proliferative nephritis and patients without renal involvement with high dsDNA binding activities revealed significantly lower complement levels in the former group. No significant difference was observed in the prevalence of antibodies to soluble cellular antigens between patients with or without renal disease; however, nRNP antibody was two-fold more frequent in patients with MGN than in all other subgroups. This study highlights the close relationship between concurrently high anti-dsDNA and low complement levels and proliferative glomerulonephritis in SLE, and suggests that subjects with MGN may represent a subgroup of SLE patients showing peculiar serological features. Different mechanisms possibly involved in the pathogenesis of MGN in SLE are discussed.

Detection of two associated precipitating autoantibodies (DA1 and DA2) in sera from patients with systemic lupus erythematosus.

In a clinical and serological study performed on a large series of patients with different connective tissue disorders, only sera from patients with systemic lupus erythematosus (SLE) contained two precipitin systems (DA1 and DA2) directed against nuclear proteins present in a total extract of human spleen. DA1 antibody appeared in 5% of SLE patients and was always associated with DA2 antibody which was found in about 22% of SLE patients. Sera monospecific for DA1 and DA2 antibodies gave a speckled staining pattern on both rat kidney and HEp2 cells. DA1-positive patients showed a higher incidence of photosensitivity (p less than 0.001), hepatosplenomegaly (p less than 0.001), hemolytic anemia (p less than 0.05), CNS involvement, vasculitis, and diffuse proliferative glomerulonephritis than DA1-negative ones. DA2-positive patients showed an increased incidence of leukopenia (p less than 0.05) and thrombocytopenia (p less than 0.01) than controls. While several indirect evidences suggest that DA1 precipitin might be identical to the previously described MA antibody, DA2 precipitin appears as a new system in SLE. The serological association between DA1 and DA2 antibodies might be analogous to the well known ones between antibodies to Sm and nRNP and to SSA/Ro and SSB/La.

Clinical findings in patients with SLE whose sera contain antibodies to ribosomal ribonucleoprotein.

In a clinical and serological study performed on a large series of patients with different connective tissue diseases, anti-ribosomal ribonucleoprotein (rRNP) antibodies were detected only in a small proportion of sera with systemic lupus erythematosus (SLE). SLE patients positive for anti-rRNP autoantibodies showed a significantly higher incidence of hemolytic anemia. The reasons for this surprising association are still unclear; however, this finding suggests that rRNP precipitin might be considered as a useful marker of a particular subgroup of patients with SLE.

Comparison between counterimmunoelectrophoresis and double radial immunodiffusion in the detection of antibodies to topoisomerase I in sera from scleroderma patients.

Sera from 146 patients with progressive systemic sclerosis have been submitted to the detection of anti-Scl 70 antibodies by both double radial immunodiffusion (ID) and counterimmunoelectrophoresis (CIE). CIE detected a significantly higher number of positive sera from patients with diffuse scleroderma, while no difference between the two techniques was noted in sera from patients with CREST variant. CIE increases the diagnostic importance of the serologic investigation in systemic sclerosis and gains a better distinction between subgroups of patients with different clinical expressions of this disease.

Anti-Epstein-Barr virus antibodies in systemic lupus erythematosus.

Sera from 18 patients with Systemic Lupus Erythematosus (SLE), 20 with nonA-nonB acute hepatitis and 19 healthy subjects were tested for the presence of antibodies to the viral capside of Epstein-Barr virus. In patients with SLE the mean titre of anti-VCA IgG was significantly higher than in normal subjects (p less than 0.02), and the percentage of patients with titres greater than 1:160 was significantly higher than in normal population (p less than 0.01). These high anti-VCA) titres in SLE patients are probably related to a defective immune surveillance.

Antibodies to Epstein-Barr virus and cytomegalovirus in primary Sjogren's syndrome.

Sera from 28 patients with Primary Sjögren's Syndrome (SS) and 20 healthy subjects were tested for the presence of antibodies to Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV). No difference was noted in the mean titre of anti-CMV antibodies in patients and in controls. For what concerns EBV, the mean titre of anti-EBNA antibodies was significantly higher in SS patients than in normals (p less than 0.001); moreover, within the SS population, titres were higher in SSB-positive than in SSB-negative patients (p less than 0.05). These results, together with the fact that anti-SSB antibodies (characteristic of Sjögren's Syndrome) recognize also two EBV-encoded RNAs, strengthen the hypothesis that EBV is involved in the pathogenesis of SS.

Autoantibody to proliferating cell nuclear antigen (PCNA) in SLE: a clinical and serological study.

In a clinical and serological follow-up study on a large series of subjects with different connective tissue disorders, anti-PCNA/cyclin autoantibodies were found in about 3% of patients with SLE. Positive subjects showed a higher incidence of diffuse proliferative glomerulonephritis and hematological disorders than the general SLE population. A highly significant serological association between PCNA and SL/Ki autoantibodies (p less than 0.001) has been observed. Persistence or disappearance of serum PCNA antibodies were independent of any clinical and serological feature or the therapeutic regimen employed.