Search

BACKGROUND Despite therapeutic advances, chronic heart failure (CHF)-related mortality and hospitalization is still unacceptably high. Evidence shows that muscular wasting, sarcopenia, cachexia are independent predictors of mortality and morbidity in CHF and are signs of protein metabolism disarrangement (PMD), which involve all body proteins including circulating one. We postulate that circulating human serum albumin (HSA) could be a marker of PMD and catabolic low-grade inflammation (LGI) in CHF patients. METHODS One hundred sixty-six stable CHF patients (73% males), with optimized therapy referred to cardiac rehabilitation, were retrospectively divided into three groups based on their HSA concentration: ≥3.5 g/dL (normal value), 3.2-3.49 g/dL (low value); ≤3.19 g/dL (severe value). Hematochemical analyses (including circulating proteins and inflammatory markers) and body mass composition (by Bioelectrical Impedance Vector Analysis) were collected and compared. Correlations and multivariate regression were performed. RESULTS Despite being overweight (BMI=27 kg/m2), 75% of patients had reduced HSA (

Management of chronic diseases in a progressively aging population is a major issue in western industrialized countries and telehealth is one way to ensure the continuity of care in chronic illness. We describe here our personal experience in a telehealth and telecare centre in Italy. Between January 2000 and December 2015, 1635 elderly patients (71% male) with one or more comorbidities have undergone a telehealth program tailored to their specific disease: chronic obstructive pulmonary disease (COPD)/chronic respiratory insufficiency; amyotrophic lateral sclerosis/neuromuscular diseases; chronic heart failure (CHF); post-stroke; and post-cardiac surgery patients discharged from hospital after an acute event. COPD and CHF represent the majority of patients treated (accounting for 80%). Interventions performed by the nurse tutor account for 39–82% of all activities in the five different programs. Specialist second opinion represents 12–27% of the health staff activities. Previously reported results show a reduction of the re-hospitalization rate and costs, and increase in quality of life and patient satisfaction with the service. A multidisciplinary telehealth and telecare integrated approach can provide efficient management for the growing number of complex patients.

The aim of this study is to gain insight into the individual experiences of patients who attempt suicide in order to better understand the reasons for and emotions behind a suicide attempt, thus also gaining insight, through the patients' own input, into the risk and protective factors which might influence possible repeat attempts and the attitude towards the assistance they receive. Two focus groups were conducted involving 17 participants, all hospitalized at the time of research for attempting suicide. The patients proved themselves competent, even expert in indicating reasons for, risk factors of and prevention strategies for suicide. The main findings suggest that the relational factor represents a key point both as a trigger for the suicide attempt and for promoting the communication of the intent or for preventing a repeat suicide attempt, as interpersonal relationships and an empathic environment were, in essence, what was perceived as therapeutic and protective and enabled the expression of thoughts and self-understanding. Accordingly psychotherapy, non-specific relationship 'monitoring' after discharge and tutored self-help groups have been suggested. Feasibility and implementing methods as well as the role of the nurse for such interventions were discussed.

International audience; PI-2301 is an immunomodulator that could be an alternative therapy for MS. A placebo-controlled, multiple-ascending dose, double-blind study was performed in patients with secondary-progressive MS. Treatment was given subcutaneously once weekly for 8 weeks, followed by a 4-week open-label treatment period with active drug. The most common adverse event was transient injection site reactions. Non-significant trend for increases in serum levels of IL-3, IL-13, and CCL22 over time were suggestive of a beneficial T(H)2 immune response in subjects dosed with PI-2301 at 3 and 10 mg. MRI data indicated a non-significant trend for a reduction of lesion numbers in subjects treated with 1 and 3 mg PI-2301. (C) 2010 Elsevier B.V. All rights reserved.

We evaluated the feasibility of a home-based rehabilitation programme, which was designed to resemble an in-hospital rehabilitation programme. Patients who underwent cardiac surgery (EuroSCORE 0–10) followed a one-month home rehabilitation programme supervised by a nurse-tutor and a physiotherapist. Physiotherapy was performed at home with calisthenic exercises and bicycle-ergometer tests. Patients transmitted the recorded ECGs by telephone to a service centre. They also performed a 6-minute walking test and filled in a satisfaction questionnaire at the end of the programme. A total of 47 patients were enrolled in the study. There were 3050 telephone calls, of which 3012 (99%) were scheduled and 38 were unscheduled. No further action was required in 95% of calls. There were 809 sessions for calisthenic exercises and 1039 for exercise training. There was a significant increase in the 6-minute walking test distance at the end of the programme compared to the baseline (404 m vs. 307 m, P < 0.001). Patient satisfaction, as measured in a questionnaire, was about 95% overall. This type of home rehabilitation using telemedicine appears to be worth implementing in selected categories of patients.

N/A

We assessed the feasibility of home-based telecardiology for patients with chronic heart failure (CHF). Seventy-four CHF patients were enrolled into a programme of telephone follow-up and single-lead electrocardiography (ECG) monitoring. The patients transmitted their ECG data by fixed telephone line to a receiving station, where a nurse was available for an interactive teleconsultation. Patients were followed up for a mean (SD) of 307 (108) days; 1467 calls were analysed (213 ad hoc consultations and 1254 scheduled consultations). A total of 124 cardiovascular events were recorded. Modifications to therapy were suggested in response to 119 calls; hospital admissions were suggested for 13 patients, further investigations for 7 and a consultation with the patient's general practitioner for 13. No action was taken after 1330 calls. Twenty-two ECG abnormalities were recorded. In 63 patients receiving the beta-blocker carvedilol, the mean dosage increased from 36 to 42 mg. In the previous year there were 1.8 hospitalizations per patient, while in the follow-up period there were 0.2 hospitalizations per patient. Following up CHF patients using a nurse-led telecardiology programme seems to be feasible and useful.

Two hundred general practitioners were equipped with a portable electrocardiograph which could transmit a 12-lead electrocardiogram (ECG) via a telephone line. A cardiologist was available 24 h a day for an interactive teleconsultation. In a 13-month period there were 5073 calls to the telecardiology service and 952 subjects with chest pain were identified. The telecardiology service allowed the general practitioners to manage 700 cases (74%) themselves; further diagnostic tests were requested for 162 patients (17%) and 83 patients (9%) were sent to the hospital emergency department. In the last group a cardiological diagnosis was confirmed in 60 patients and refuted in 23. Seven patients in whom the telecardiology service failed to detect a cardiac problem were hospitalized in the subsequent 48 h. The telecardiology service showed a sensitivity of 97.4%, a specificity of 89.5% and a diagnostic accuracy of 86.9% for chest pain. Telemedicine could be a useful tool in the diagnosis of chest pain in primary care.

Our aim was to examine, using microsatellite (ms) markers, the contribution of the telomeric part of the HLA region to rheumatoid arthritis (RA) predisposition in the Spanish population. We have looked at the distribution of DQB1, DRB1 and five ms loci ( D6S1014, D6S273, D6STNFa, MIB and C1-2-5 ) within the HLA region in 147 Spanish RA patients and 202 control subjects. A total of 19 conserved ms configurations were observed, twelve of them in linkage disequilibrium with particular DQB1-DRB1 haplotypes. Interestingly, haplotype c1 ( DQB1*0201-DRB1*0301-D6S1014*143-D6S273*139-D6STNFa*99-MIB*350-C1-2-5*196 ) was significantly associated with RA predisposition. As part of this haplotype, the MIB *350 allele was found to be a risk factor independently of the RA-predisposing haplotypes. The present results along with data from others prove the existence of a second predisposing locus located inside the MHC region, and suggest that might be located within the TNFa-HLA-B region.

Objectives: (a) To describe the clinical characteristics of acute sarcoid arthritis and the diagnostic value of its presenting clinical features; (b) to evaluate whether disease onset is seasonal; and (c) to evaluate whether smoking behaviour or the presence of HLA class II alleles is a risk factor for the disease. Methods: 579 consecutive patients with recent onset arthritis who had been newly referred to a rheumatology outpatient clinic were included in a prospective cohort study. The presenting clinical features, the smoking behaviour, and the results of HLA-DQ and HLA-DR DNA typing of 55 patients with sarcoid arthritis, 524 patients with other arthritides of recent onset, and samples of the normal population were compared. Results: In all cases the disease showed a self limiting arthritis and overall good prognosis. The diagnostic ability of a combination of four clinical features—symmetrical ankle arthritis, symptoms of less than two months, age below 40 years, and erythema nodosum—was exceptionally high. When test positivity is defined as the presence of at least three of four criteria the set rendered a sensitivity of 93%, a specificity of 99%, a positive predictive value of 75%, and a negative predictive value of 99.7%. The disease clustered in the months March–July. The disease was negatively associated with smoking (odds ratio (OR) 0.09; 95% confidence interval (95% CI) 0.02 to 0.37) and positively associated with the presence of the DQ2 (DQB1*0201)-DR3 (DRB1*0301) haplotype (OR 12.33; 95% CI 5.97 to 25.48). Conclusion: The disease entity acute sarcoid arthritis has highly diagnostic clinical features. The seasonal clustering, the protective effect of smoking, and the association with specific HLA class II antigens support the hypothesis that it results from exposure of susceptible hosts to environmental agents through the lungs.

Experimental studies in transgenic mice have suggested that HLA-DQ predisposes to rheumatoid arthritis (RA), but could also modulate disease severity by presenting peptides derived from self-DR molecules. In particular, a short amino acid sequence, 70 DERAA 74 , in the third hypervariable region of HLA-DRB1 confers protection for the disease, while particular HLA-DQ [DQB1∗0501/DQA1∗01 (DQ5) and DQB1∗03/DQA1∗03 (DQ3)] molecules predispose to the disease. We have therefore analyzed the allelic distribution of HLA-DRB1, DQA1, and DQB1 and the presence of rheumatoid factor and nodules among 199 German RA patients and 196 healthy controls. Our results show that HLA-DQB1∗03/DQA1∗03 (or DRB1∗04) predisposes to RA more than HLA-DQB1∗0501/DQA1∗01 ( i.e ., DRB1∗01 and DRB1∗10). Homozygosity for DQ3 confers the strongest genetic risk for RA (OR = 19.79 compared to OR = 10.05 for two doses of shared epitope (SE) positive HLA-DRB1 alleles). Furthermore, patients carrying both predisposing DQ and 70 DERAA 74 -positive HLA-DRB1 alleles are more often rheumatoid factor (RF) negative than patients carrying predisposing DQ alleles alone. Only one out of 14 patients (7%) with a protective combination (DQ3/ 70 DERAA 74 and DQ5/ 70 DERAA 74 ) had rheumatoid nodules compared to 67 out of 144 patients (46.5%) with predisposing DQ alleles alone (OR = 0.12, 95% CI: 0.02–0.72, p = 0.004). These results demonstrate a protective role of 70 DERAA 74 -positive DRB1 alleles against disease severity among RA patients.

Objective. To analyse the distribution of predisposing DQ3 (DQB1 * 03( * 04)/DQA1 * 03) and DQ5 (DQB1 * 0501/DQA1 * 01), shared epitope encoding and protective DRBI alleles in patients with early rheumatoid arthritis (RA) and undifferentiated arthritis (UA), Methods. Consecutive patients enrolled in an early arthritis clinic were DNA-typed for HLA-DQ and DR. RA patients (n = 195), UA patients (n = 160) and controls from the same region (n = 306) were sorted according to their DQ-DR phenotypes: DQ3 vs DQ5 and the presence or absence of a protective DERAA-positive DRB1 molecule. The three groups were also sorted according to the shared epitope (SE) hypothesis. Results. We observed the association of both DQ3 and DQ5 with RA. DQ3 3 homozygous individuals had the highest risk of developing disease [odds ratio (OR) = 20.00]. Conversely DQ5. but not DQ3, was associated with undifferentiated arthritis (OR = 2.15 vs 1.25). Consistent with these differences, DQ3-positive individuals had significantly more active disease at the first visit at the outpatient clinic than DQ5-positive patients. DRBI alleles encoding a DERAA motif in their third hypervariable region provided a strong dominant protection against RA among DQ5-positive individuals and decreased arthritis activity among DQ3-positive patients. Individuals with SE-positive DR1, DR4 and DR10 alleles were also predisposed to RA, DR4 4 homozygous individuals having the highest risk of developing RA (OR = 11.00). Conclusion. The DQ3-DR4/9 haplotypes are associated with RA. The DQ5-DRI/10 haplotypes are associated with less active disease, i.e. UA, and DERAA encoding DRBI alleles modulate either predisposition to or the severity of RA. We propose that HLA polymorphism influences not only the initiation or perpetuation of RA but also protection against the disease.

Objective To evaluate the contributions of HLA–DQ and –DR polymorphisms to susceptibility to rheumatoid arthritis (RA) in a population in southern Spain, and to compare the value of the shared epitope (SE) and RA protection (RAP) models in accounting for the HLA class II region's contribution to RA predisposition. Methods One hundred sixty RA patients and 153 healthy controls were typed for HLA–DRB1 and –DQB1 using high-resolution DNA techniques. Distributions of predisposing DRB1 alleles in patients and control subjects according to the SE model were compared with distributions of predisposing DQ and protective DERAA-positive DRB1 alleles according to the RAP model. Results DQ3 (DQB1*03 and *04 combined with DQA1*03) and DQ5 (DQB1*0501/DQA1*0101) alleles predisposed individuals to RA independently of SE-positive DRB1 alleles. DQ3/3-homozygous individuals had the strongest risk of developing RA. DQ3 molecules predisposed to RA more than did DQ5 molecules. The weaker predisposition mediated by DQ5 included the DRB1*1001-carrying haplotype; no DRB1*1001-homozygous patients were observed. DRB1*0401 played a unique role in the contribution of DQ3–DR4 haplotypes to RA, in spite of its low frequency in southern Spain. Conclusion The low prevalences of RA and of mild disease observed in Spain, and in southern Europe in general, can be explained in great part by the low frequency of DQ3–DR4 haplotypes, especially those carrying DRB1*0401. However, the overall distribution of HLA–DQ and –DR alleles in RA patients compared with control subjects is similar to that in other European and North American populations. A model involving both DQ and DR can best account for the contribution of HLA to RA.

We have reviewed the literature on the association of HLA class II with rheumatoid arthritis (RA). Strong linkage disequilibrium among DQB1, DQA1 and DRB1 alleles makes it difficult to evaluate the individual contribution of each locus. Nonetheless, there is a strong case for the role of DQB1∗03 and ∗04 combined with DQA1∗03 in susceptibility to severe RA while DQB1∗0501 combined with DQA1∗0101 and ∗0104 weakly predisposes to a mild form of RA. However, it is also clear that DRB1∗0401 has a particular role in predisposition to the most severe form of the disease while other DRB1 alleles might provide protection. We would like to propose that in RA, as in type I diabetes, both DQ and DR loci contribute to predisposition to the disease.

Objective To evaluate the respective contributions of tumor necrosis factor (TNF) promoter polymorphisms and HLA–DR alleles to susceptibility to systemic lupus erythematosus (SLE). Methods TNF-238G/A and 308G/A promoter polymorphisms and HLA–DRB1 alleles were determined in 99 consecutive Caucasian SLE patients and 177 Caucasian controls. Standard and Mantel-Haenszel odds ratios were calculated to assess the magnitude of the susceptibility factors. The presence or absence of the SLE classification criteria was determined and correlated with the TNF promoter and HLA–DRB1 genotypes. Results The frequency of the TNF-308A/A and 308G/A genotypes was significantly higher in SLE patients (odds ratio 5.0). Conversely, TNF-238G/A and 238A/A genotypes were equally prevalent in SLE patients and controls. The HLA–DR3 specificity (DRB1*0301 allele) was significantly more prevalent in the SLE population (odds ratio 4.4). Stratification to correct for interdependence of the 2 loci confirmed the association of both TNF-308A and HLA–DR3 with SLE (Mantel-Haenszel odds ratio 3.2 and 2.4, respectively). No correlation was found between TNF promoter and HLA–DRB1 genotypes and any SLE classification criterion or disease manifestation. Conclusion TNF-308A and HLA–DR3 alleles are independent susceptibility factors for SLE.

Chronic hypoxaemia can play a pathological role in abnormalities of the autonomic nervous system (ANS). In patients with chronic obstructive pulmonary disease (COPD), chronic hypoxaemia is associated with increased mortality and only long-term oxygen therapy is able to improve their survival. Normoxaemic COPD patients have been shown to suffer from abnormalities in ANS function. The aims of this study were to evaluate ANS function in COPD patients with chronic hypercapnic respiratory insufficiency and to test whether oxygen supplementation could reverse any ANS dysfunction. Eleven stable COPD patients with chronic hypercapnic respiratory insufficiency underwent evaluation of ANS by analysis of variability in cardiac frequency at rest and during both vagal (controlled breathing) and sympathetic (tilting) stimuli breathing with and without oxygen supplementation. Thirteen male, healthy, nonsmoking volunteers served as controls. Evaluation of ANS in COPD patients during hypoxic conditions showed alterations both at rest and in response to vagal and sympathetic stimuli. Oxygen supply reversed hypoxaemia without significant changes in arterial carbon dioxide tension and, therefore, ANS alterations were corrected during sympathetic stimulus only. Breathing room air and oxygen, the resting low-frequency (LF) powers were 45+/-15 and 148+/-55 ms2 x Hz(-1), respectively, and controlled breathing LF were 107+/-41 and 141+/-113 ms2 x Hz(-1), respectively. In stable patients with chronic obstructive pulmonary disease with chronic respiratory insufficiency, hypoxaemia is associated with derangements in the autonomic nervous system which may be partially reversed by oxygen administration.

Autonomic dysfunction seems to be involved in the progression and prognosis of congestive heart failure. Measurement of heart rate variability (HRV) provides a noninvasive method to obtain reliable and reproducible information on autonomic modulation of heart rate, but there is a difficulty in using HRV as a quantitative estimate of autonomic dysfunction in heart failure. This study was aimed at testing the hypothesis that abnormal modulation of heart rate assessed by power spectrum analysis may be present also in asymptomatic patients with left ventricular dysfunction and progress in patients with overt symptoms of congestive heart failure. HRV was measured in three groups of subjects: Group 1: 30 patients with chronic heart failure; Group 2: 21 patients with asymptomatic left ventricular dysfunction; and Group 3: 25 healthy volunteers as control group. HRV was evaluated by autoregressive spectral analysis with 600-beat ECG samples, while subjects were quietly recumbent (BS1), in conditions of controlled breathing (15 acts/min) (RSC) and passive orthostatism after tilting (80°) (TLT). Patients in group 1 showed a reduction in the standard deviation of the R–R intervals (SDRR) ( p p p p p p p

We have reviewed a multidisciplinary, home-based, telecardiology service which has been used for follow-up of patients discharged early from hospital. In seven years of activity 12,576 calls have been received by 896 cardiac patients following the home based telecardiology programme: 239 patients with acute cardiac syndrome, 427 patients with chronic heart failure and 230 patients with arrhythmia. Follow-up ranged from 7–180 days. From the user's first contact with the call centre to the recording of the report took a mean time of 7–10 min. The telemedicine service is provided by a total of 14 service centre operators, 49 medical specialists, 39 nurses and 4 physiotherapists. In our experience, Web services are ideal to develop and to manage telemedicine services.

Recently, we have proposed that the combination of HLA-DQ and -DR alleles is responsible for the association of the HLA class II region with rheumatoid arthritis (RA). According to this model, some HLA-DQ alleles, namely DQ4, DQ7, DQ8, and DQ9, predispose carriers to severe RA, but a self peptide of sequence KDILEDERAAVDTYC from the third hypervariable (HV3) region of some DRB1 alleles, including DRB1*0402, can protect from the disease if presented by DQ molecules. This model implies that DQ4, DQ7, DQ8, and DQ9 should be able to present a set of common peptides, despite polymorphisms in their Ag binding groove. In the present study, we have further analyzed the immunogenicity of the DRB1*0402 HV3 peptide in DQ8-transgenic mice. We found that the motif DERAA guarantees DQ8-restricted immunogenicity, and that R is the main anchor residue for binding of the DRB1*0402 peptide to DQ. Interestingly, the p1 pocket that probably controls binding of the R residue is identical in all four RA-associated DQ molecules. Our results imply that the association of RA with some DR subtypes can be explained by their linkage with DQ alleles displaying a binding site for similar "arthritogenic" peptides.

Background Exercise rehabilitation after cardiac surgery has beneficial effects, especially on a long-term basis. Rehabilitative programs with telemedicine plus appropriate technology might satisfy the needs of performing rehabilitation at home. Objective The purpose of this study was to compare exercise capacity after home-based cardiac rehabilitation (HBCR) or in-hospital rehabilitation in patients at low to medium risk for early mortality (EuroSCORE 0–5) following cardiac surgery. Design A quasi-experimental study was conducted. Methods At hospital discharge, patients were given the option to decide whether to enroll in the HBCR program. Clinical examinations (electrocardiography, cardiac echo color Doppler, chest radiography, blood samples) of patients in the HBCR group were collected during 4 weeks of rehabilitation, and exercise capacity (assessed using the Six-Minute Walk Test [6MWT]) was assessed before and after rehabilitation. A group of patients admitted to the in-hospital rehabilitation program was used as a comparison group. Patients in the HBCR group were supervised at home by a medical doctor and telemonitored daily by a nurse and physical therapist by video conference. Periodic home visits by health staff also were performed. Results One hundred patients were recruited into the HBCR group. An equal number of patients was selected for the comparison group. At the end of the 4-week study, the 2 groups showed improvement from their respective baseline values only in the 6MWT. No difference was found in time × group interaction. Limitations Because patients self-selected to enroll in the HBCR program and because they were enrolled from a single clinical center, the results of the study cannot be generalized. Conclusions In patients who self-selected HBCR, the program was found to be effective and comparable to the standard in-hospital rehabilitative approach, indicating that rehabilitation following cardiac surgery can be implemented effectively at home when coadministered with an integrated telemedicine service.

The aim of this study is to gain insight into the individual experiences of patients who attempt suicide in order to better understand the reasons for and emotions behind a suicide attempt, thus also gaining insight, through the patients' own input, into the risk and protective factors which might influence possible repeat attempts and the attitude towards the assistance they receive. Two focus groups were conducted involving 17 participants, all hospitalized at the time of research for attempting suicide. The patients proved themselves competent, even expert in indicating reasons for, risk factors of and prevention strategies for suicide. The main findings suggest that the relational factor represents a key point both as a trigger for the suicide attempt and for promoting the communication of the intent or for preventing a repeat suicide attempt, as interpersonal relationships and an empathic environment were, in essence, what was perceived as therapeutic and protective and enabled the expression of thoughts and self-understanding. Accordingly psychotherapy, non-specific relationship 'monitoring' after discharge and tutored self-help groups have been suggested. Feasibility and implementing methods as well as the role of the nurse for such interventions were discussed.

Thyroglobulin is the major Ag of the thyroid gland involved in autoimmune pathologies. Epitope mapping was carried out with a rabbit polyclonal immune serum against fusion proteins expressed in prokaryotic cells. After screening of an initial human thyroglobulin cDNA library and subcloning of immunoreactive clones, seven epitopes were characterized and localized on the human thyroglobulin monomeric molecule. One was close to each extremity of the molecule, and five others were concentrated in the middle, covering a sixth of this 2748-amino-acid chain. The immunoreactivities of 18 autoimmune sera from different thyroid pathologies were tested against the seven previously characterized epitopes. Those from Hashimoto's thyroiditis were the most immunoreactive. Immune responses were heterogeneous for sera from different pathologies as well as for those from the same pathology. The central epitopes and the near-C-terminal epitope, however, were the epitopes most often recognized by the immune sera. These findings show that some autoepitopes overlap accurately with some heteroepitopes characterized by a polyclonal immune serum directed against the mature protein.

An initial lambda gt 11 cDNA library constructed from a human Graves' patient thyroid was screened with an immunopurified rabbit anti-human thyroperoxidase (hTPO) polyclonal antibody. A 869 bp clone was obtained. It presents a 130 bp deletion as compared to the published sequence and a 77 bp insertion in the 3' non-coding region. Screening of a pUC cDNA library from another Graves' patient thyroid exhibited the same 130 bp deletion in two other cDNA clones. PCR analysis of mRNA transcripts confirmed the presence of the two messengers in two other Graves' thyroid tissues. In all the cases, this new spliced mRNA species represents between 40% and 50% of the total hTPO mRNAs. With respect to the structure of the hTPO gene, the present deletion suggests an alternate splicing of exon 16. The juxtaposition of exon 17 to exon 15 encoding the transmembrane domain leads to a shift in the reading frame. By the use of a different stop codon, the spliced mRNA generates a modified 56 - COOH terminal aminoacids (aa) sequence.

Background Chronic heart failure (CHF) remains a common cause of disability, death and hospital admission. Several investigations support the usefulness of programs of disease management for improving clinical outcomes. However, the effect of home-based telemanagement programs on the rate of hospital readmission is still unclear and the cost-effectiveness ratio of such programs is unknown. The aim of the study was to determine whether a home-based telemanagement (HBT) programme in CHF patients decreased hospital readmissions and hospital costs in comparison with the usual care (UC) follow-up programme over a one-year period. Methods and results Four hundred-sixty CHF patients (pts), aged 57±10 years were randomised to two management strategies: 230 pts to HBT programme and 230 pts to UC programme. The HBT pts received a portable device, transferring, by telephone, a one-lead trace to a receiving station where a nurse was available for interactive teleconsultation. The UC pts were referred to their primary care physicians and cardiologists. The primary objective of the study was one-year hospital readmission for cardiovascular reasons. During one-year follow-up 55 pts (24%) in HBT group and 83 pts (36%) in UC group had at least one readmission (RR=0.56; 95% CI: 0.38–0.82; p =0.01). After adjusting for clinical and demographic characteristics, the HBT group had a significantly lower risk of readmission compared with the UC group (HR=0.50, 95% CI: 0.34–0.73; p =0.01). The intervention was associated with a 36% decrease in the total number of hospital readmissions (HBT group: 91 readmissions; UC group: 142 readmissions) and a 31% decrease in the total number of episodes of hemodynamic instability (101 in HBT group vs 147 in UC group). The rate of hearth failure-related readmission was 19% (43 pts) in HBT group and 32% (73 pts) in UC group (RR=0.49, 95% [CI]: 0.31–0.76; p =0.0001). No significant difference was found on cardiovascular mortality between groups. Mean cost for hospital readmission was significantly lower in HBT group (€ 843+/−1733) than in UC group (€ 1298+/−2322), (−35%, p Conclusions This study suggests that one-year HBT programme reduce hospital readmissions and costs in CHF patients.

Palpitation is a common symptom that sometimes results from a substantial cardiac arrhythmia. We compared the diagnostic yield of trans-telephonic event monitors with those of Holter monitoring in patients with intermittent palpitations. In all, 310 patients were randomly assigned to receive an event recorder or 24–hour Holter monitoring. Event recorders were used for seven days or until two recordings were obtained while symptoms occurred. The main end-point was an electrocardiogram (ECG) recorded during symptoms. The patients with palpitation recorded the one-lead ECG trace and sent it to a telemedicine call centre, where a nurse responded. There were 119 symptomatic patients in the event recorder group and 74 in the Holter group. The total costs were €6019 for event recording and €9605 for Holter monitoring. The average costs were €51 per symptomatic patient detected by event recorder monitoring and €1 30 per symptomatic patient detected by Holter monitoring. More patients therefore received a clear diagnosis, and more quickly, when using event recording than with Holter monitoring. For this reason, event recorders are preferable to Holter monitors for patients with palpitations.

Chronic heart failure (CHF) remains a common cause of disability. We have investigated the use of home-based telecardiology (HBT) in CHF patients. Four hundred and twenty-six patients were enrolled in the study: 230 in the HBT group and 196 in the usual-care group. HBT consisted of trans-telephonic follow-up and electrocardiogram (ECG) monitoring, followed by visits from the paramedical and medical team. A one-lead ECG recording was transmitted to a receiving station, where a nurse was available for reporting and interactive teleconsultation. The patient could call the centre when assistance was required (tele-assistance), while the team could call the patient for scheduled appointments (telemonitoring). The one-year clinical outcomes showed that there was a significant reduction in rehospitalizations in the HBT group compared with the usual-care group (24% versus 34%, respectively). There was an increase in quality of life in the HBT group (mean Minnesota Living Questionnaire scores 29 and 23.5, respectively). The total costs were lower in the HBT group (107,494 and 140,874, respectively). The results suggest that a telecardiology service can detect and prevent clinical instability, reduce rehospitalization and lower the cost of managing CHF patients.

We investigated a home-based intervention based on telecardiology in patients with chronic heart failure (CHF). Two hundred and thirty CHF patients, aged 59 years (SD 9), in stable condition and with optimized therapy were enrolled. The programme consisted of trans-telephonic follow-up and electrocardiogram (ECG) monitoring followed by visits from a paramedical and medical team. The patient could call the centre when required (tele-assistance), while the team could call the patient at pre-scheduled times (telemonitoring). During the first 12 months, there were 3767 calls (873 ad hoc and 2894 scheduled calls). There were 648 events, including 126 episodes of asymptomatic hypotension and 168 episodes which were not due to cardiological symptoms. No actions were taken by the nurse after 2417 calls (64%). A change in therapy was suggested after 418 calls, hospital admission in 62 patients, further investigations for 243 patients and a consultation with the general practitioner in 41 patients. A total of 2303 one-lead ECG recordings were received (10 per patient); 126 recordings (6%) were diagnosed as pathological in comparison with the baseline one. The one-lead ECG recording was used for titration of beta-blockers in 79 patients (mean dosage 38 mg vs 42 mg, P

Contains fulltext : 58480.pdf (Publisher’s version ) (Closed access) Objective. The functional role of HLA class II molecules in the pathogenesis of rheumatoid arthritis (RA) is unclear. HLA class II molecules are involved in the interaction between T and B lymphocytes required for long-lived B cell responses and generation of high-affinity IgG antibodies. We undertook this study to investigate the relationship between HLA class II gene polymorphisms and RA-specific IgG antibodies against cyclic citrullinated peptides (anti-CCP antibodies). Methods. High-resolution HLA-DR and DQ typing and anti-CCP-2 antibody testing were performed on 268 RA patients from the Early Arthritis Clinic cohort at the Department of Rheumatology of the Leiden University Medical Center. The presence of anti-CCP antibodies was analyzed in carriers of the different DR and DQ alleles. Disease progression was measured over a period of 4 years by scoring radiographs of the hands and feet using the Sharp/van der Heijde method. Results. Carriership of the individual alleles HLA-DRBt*0401, DRB1*1001, DQB1*0302, and DQBI*0501 was associated with the presence of antiCCP antibodies. Carriers of DQ-DR genotypes containing proposed RA susceptibility alleles were significantly more often anti-CCP antibody positive. Carriership of one or two HLA-DRB1 shared epitope (SE) alleles was significantly associated with production of anti-CCP antibodies (odds ratio [OR] 3.3, 95% confidence interval [95% CI] 1.8-6.0 and OR 13.3, 95% CI 4.6-40.4, respectively). An increased rate of joint destruction was observed in SE+, anti-CCP+ patients (mean Sharp score 7.6 points per year) compared with that in SE-, anti-CCP+ patients (2.4 points per year) (P = 0.04), SE+, anti-CCP- patients (1.6 points per year) (P < 0.001), and SE-, anti-CCP- patients (1.6 points per year) (11 < 0.001). Conclusion. HLA class II RA susceptibility alleles are associated with production of anti-CCP antibodies. Moreover, more severe disease progression is found in RA patients with both anti-CCP antibodies and SE alleles.

Background: Atrial fibrillation (AF) is the most common sustained cardiac tachyarrhythmia and is often an occasional diagnosis in the absence of known cardiac disease. The aim of this study is to describe an Italian patient population with AF followed by their General Practitioners (GPs) using a telecardiology service. Methods: A total of 655 Italian GPs were equipped with a portable electrocardiographer. The ECG tracing of all consecutive patients (7516) received between January and September 2001 was included into the study. Results: AF was detected in 719 patients (9.%) (77±12 years). In 448 patients, it was a known chronic condition, while in 271 patients, it was a new diagnosis. In the chronic AF, the principal reason for the teleconsultation was a routine control by the GPs, but an uncontrolled cardiac rate was present in 29% of the cases, while an antiplatelet or anticoagulation therapy was administered in only 46.2% cases. The teleconsultation alone provided a solution to the GPs' requests in 348 patients (77.6%) (154 cases (34.5%) required no further action while 194 patients (43.5%) needed therapy adjustments only), while 47 patients (10.5%) required hospitalization and 51 patients needed further diagnostic tests. In 271 cases, a first evidence of atrial fibrillation was recorded: in 259 patients, GPs requested a teleconsultation in the presence of symptoms (mainly palpitation, dyspnoea and fatigue) and in 12 for routine control; in this case, 121 patients (46.9%) needed Emergency Department (ED) admission, 113 patients (39.1%) needed therapy adjustments and, for 19 patients (7.5%), further diagnostic tests were prescribed. Conclusion: In Italy, many patients, in particular the elderly, with AF are followed by their GPs on a routine basis; a telecardiology service may provide a useful tool in the home management of chronic AF and in the first detection of new cases of AF.

Telephone linked care technology has been developed and applied as a supplement for ambulatory visits, as a means to offer a specific cardiac diagnosis during a general family doctors' visit. The method was as follows: from February to July 1998, 178 family doctors had a mobile electrocardiogram (Card Guard 7100) which was able to transmit via any fixed or mobile telephone to a center where a cardiologist was present for the analysis of the ECG and for an interactive opinion. During the first six months 2254 patients were enrolled (mean age 63/spl plusmn/8 years), 609 patients (27%) had systemic hypertension, 283 patients (12%) had ischemic cardiac disease and 850 (37%) had no evidence of previous cardiopathy. In this paper the results of the subgroup with known coronary artery disease were analysed. In this subgroup 157 patients (55%) were asymptomatic at the moment of ECG recording, while 126 patients (45%) referred chest pain in 54 (43%), dyspnoea in 34 (27%), dizziness in 15 (12%), asthenia in 15 (12%) and palpitation in 10 (8%). No actions were taken in 179 (63%) of the patients; 22 patients (8%) were addressed to the emergency department in 25 patients (9%) were suggested further investigations and in 57 patients (20%) a new therapy or a therapeutic change was suggested. In conclusion, telemedicine is an useful tool to support family doctors in the diagnosis of the cardiac disease.

Item does not contain fulltext OBJECTIVE: CD4+,CD25+ T regulatory cells may offer opportunities to intervene in the course of autoimmune disease. We wished to evaluate their potential for influencing systemic and chronic joint inflammation by investigating their involvement in collagen-induced arthritis (CIA). METHODS: We depleted DBA/1 mice of CD25+ regulatory cells by injection of a depleting monoclonal antibody specific for CD25 14 days before a single immunization with type II collagen (CII) in Freund's complete adjuvant. CD4+,CD25+ T cells were adoptively transferred to some groups of mice during immunization. Mice were then scored for signs of arthritis, and blood was taken periodically to measure the amounts of CII-specific antibodies. Splenocytes of treated mice were examined in vitro to determine the effects of depletion on proliferation to CII and control antigens. RESULTS: CD25+ cell-depleted DBA/1 mice had significantly more severe disease than control mice following collagen immunization. The magnified severity was also accompanied by higher antibody titers against collagen, and in vitro tests showed increased proliferation of collagen-specific T cells. Adoptively transferring CD4+,CD25+ T cells into depleted mice was shown to reverse the heightened severity. Control mice, which were depleted and immunized with the neoantigen keyhole limpet hemocyanin (KLH), had neither an increased antibody response toward KLH nor an augmented proliferative response, indicating that CD25+ cell depletion preferentially affects immunity against self antigen. CONCLUSION: These results establish a link between CD4+,CD25+ regulatory cells and CIA and provide a rationale for investigating CD4+,CD25+ T regulatory cells in the treatment and prevention of arthritis.

Our aim was to examine, using microsatellite (ms) markers, the contribution of the telomeric part of the HLA region to rheumatoid arthritis (RA) predisposition in the Spanish population. We have looked at the distribution of DQB1, DRBI and five ms loci (D6S1014, D6S273, D6STNFa, MIB and C1-2-5) within the HLA region in 147 Spanish RA patients and 202 control subjects. A total of 19 conserved ms configurations were observed, twelve of them in linkage disequilibrium with particular DQB1-DRB1 haplotypes. Interestingly, haplotype c1 (DQB1*0201-DRB1*0301-D6S1014*143-D6S273*139-D6STNFa*99-MIB*350-C1-2-5*196) was significantly associated with RA predisposition. As part of this haplotype, the MIB*350 allele was found to be a risk factor independently of the RA-predisposing haplotypes. The present results along with data from others prove the existence of a second predisposing locus located inside the MHC region, and suggest that might be located within the TNFa-HLA-B region.

Here we report an additional source of variation resulting from genetic polymorphism in HLA-DQbeta1 genes, namely, allelic diversity in the first exon of the HLA-DQB1 locus, which encodes the leader peptide sequence. Six different variants, including a novel polymorphic site, were detected among the DBQ1 haplotypes.

Human leukocyte antigen (HLA)-DR2 carriership is associated with an increased risk for MS. Genome searches using microsatellite markers have consistently shown that additional genetic factors contribute to susceptibility for MS.To identify loci within the HLA region that predispose to relapse-onset MS independently of HLA-DR2.A case-control study involving 159 patients with definite relapse-onset MS and 273 control subjects was conducted. Six highly polymorphic microsatellite markers encoded within the HLA-C to DR region, that is, D6S1014, D6S273, TNFa, MIB, C1_2_5, and C1_3_2, three single-nucleotide tumor necrosis factor (TNF) promoter gene polymorphisms at positions -238, -308, and -376, and HLA-DR2 carriership were typed.These data confirmed the well-known association between the HLA-DR2 haplotype and relapse-onset MS, yielding an odds ratio (OR) of 3.6 (95% CI: 2.4 to 5.4; p0.0001). Multivariate analyses revealed that C1_3_2*354 was also associated with an increased risk for developing relapse-onset MS independently of HLA-DR2 (OR: 2.0; 95% CI: 1.2 to 3.1; p = 0.004). This allele is encoded within an ancestral haplotype that is highly linked to HLA-DR3. The joint effect of this ancestral haplotype and HLA-DR2 resulted in an OR of 8.7 (95% CI: 2.7 to 29; p0.0001) to develop relapse-onset MS. In addition, a protective risk factor was found: carriers of TNFa*107 had a 0.5-fold lower risk to develop relapse-onset MS (95% CI: 0.3 to 0.9; p = 0.026).Within the HLA region, other loci besides HLA-DR2 haplotype modulate susceptibility for relapse-onset MS.

Rising health care costs resulted in increasing pressure on the health care system and stimulated new strategies for improving the efficiency of care. A telecardiology service provides a useful support to general practitioners in the management of cardiac patients and contributes to the optimization of health care costs in terms of appropriateness of hospital admission and diagnostic testing. The aim of our study was to evaluate the reduction in the number of referrals to the Emergency Department and to cardiological evaluation resulting from the employment of a telecardiology service by general practitioners.Eight hundred and ninety-one consecutive calls arrived to the receiving station of the telecardiology service were analyzed. One hundred and fifty general practitioners received a portable electrocardiographer (Card-Guard 7100, Rehovot, Israel) transferring, by a mobile or fixed telephone, a 12-lead ECG to a receiving station, where a cardiologist was available for reporting and for interactive teleconsultation. At the onset of the phone call, a question was asked to the general practitioner: "What would you have done without the telecardiology service?". The possible answers were: "No actions"; "Referral to the Emergency Department"; "Cardiological consultancy"; "Further investigations". Then we collected the history, risk factors, symptoms and therapy of the patients; the general practitioner sent the ECG tracing by phone.Eight hundred and ninety-one patients were enrolled (402 males, 489 females, mean age 59 +/- 19 years); 465 (52%) patients were symptomatic; 36.4% had no evidence of previous cardiac disease, 35.1% had systemic hypertension, 10.6% had ischemic cardiac disease, 3.7% had atrial fibrillation, and 11.9% other diseases. ECG was normal in 55%. The general practitioners would have sent to the Emergency Department 106 patients (11.9%), and requested further investigations in 717 patients (80.5%). The cardiologist of the telecardiology service solved the problems of the general practitioners in 657 cases (73.7%), sent 56 patients (6.3%) to the Emergency Department, and asked for further investigations in 178 patients (20%), with a reduction of 47% of Emergency Department admission (p0.001) and of 95% of further investigations (p0.0001) respectively. The cost analysis showed a reduction, between the two modalities, varying from Itl 22,760,000 and Itl 140,060,000 for 891 calls.Telemedicine is a useful tool for the support of general practitioners' daily activity, with a possible cost reduction due to increased appropriateness of hospital admission and of diagnostic testing.

Background Allelic imbalance at polymorphic loci within the human HLA-DRB1 and TNF genes has been observed in association with increased susceptibility to systemic lupus erythematosus. Objectives We investigated whether the association of HLA-DRB1*0301 (HLA-DR3) and TNF-308A with SLE could be attributed to linkage to six polymorphic microsatellites between HLA-DRB1 and HLA-C. Methods Ninety-one consecutive Caucasian patients with SLE and 253 controls (organ donors) were typed for HLA-DRB1, D6S1014, D6S273, TNFa, MIB, C-1–2–5 and C-1–3–2 and for TNF promoter polymorphisms. Independent contribution of alleles to disease susceptibility was estimated by crosstabulation and multivariate regression. Results Carriership of TNF-308A was associated with susceptibility to SLE (odds ratio [95% confidence interval], 3.70 [2.24–6.11]). This remained present after stratification on carriership of HLA-DR3 (pooled odds ratio, 2.53 [1.37–4.70]). Stratification further revealed a possible association of carriership of C-1–2–5*192 with protection from SLE beyond the effects of HLA-DR3 and TNF-308A. Gene dose effect was observed for -308A only (homozygotes, 7.75 [3.01–20.0], heterozygotes, 3.15 [1.85–5.37]). In multivariate analysis, the association between HLA-DR3, TNF-308A, and C-1–2–5*192 remained independently associated with susceptibility to SLE (2.58 [1.29–5.18], 2.76 [1.43–5.31], and 0.26 [0.10–0.66], respectively). Conclusion An association of carriership of TNF-308A with susceptibility to SLE can not be attributed to linkage to HLA-DR3, nor to other polymorphic markers in the vicinity of the TNF gene. Further loci that are independently associated with SLE might be located in the vicinity of marker C-1–2–5.

Genetic factors contribute both to the development and the course of Rheumatoid Arthritis (RA). The contribution of inherited genetic variability has been estimated 60%. Moreover, stochastic processes during the development of the T and B lymphocytes repertoire or so-called somatic genetic diversity may be responsible for an as yet unknown fraction of the remaining 40% of the factors contributing to the pathogenesis of RA. Thus far, the only known inherited genetic factors are encoded by the HLA system. These factors contribute about 40% of the inherited genetic variability and also contribute to the somatic genetic diversity. The main contribution of the HLA system is conferred by the HLA class II region and HLA-DR genes are certainly involved but HLA-DQ genes also may have a contribution. Perhaps most importantly: certain HLA-DR genes may provide dominant protection. HLA genes not only contribute to the development but also the course and severity of RA. There is also evidence for dominant protection against the development of erosions. We observed that this effect may be relatively short-lasting and overruled by a very early start of treatment with DMARDS (Yard et al., submitted for publication). These observations suggest that pharmacogenomics may offer possibilities for a tailor-made optimal treatment for individual RA patients. The standard hypothesis for an association of an HLA class II allele with an auto-immune disease is that auto-reactive T cells recognise certain self-epitopes that are exclusively or preferentially presented by that particular HLA class II allele. The Shared Epitope (SE) hypothesis (Gregersen et al. 1987) is a paradigm of this. More than 20 years of intensive research along these lines have however yielded little evidence for this concept. Therefore, we have developed an alternative hypothesis. In this hypothesis auto-reactive T cells do not play a role in the initiation but in the regulation of the disease process (Zanelli et al., Rheumatology, in press). Our model is an extension of the one proposed by Thomas and Lipsky (Immunology Today 1996; 17: 559–560). It starts with activation of synoviocytes by a trauma or an infection. Usually this results in a local inflammation that resolves in a few days, but in the presence of one or more (yet to be identified) genetic factors (not HLA class II) an aberrant activation of synoviocytes results in a chronic inflammation. As proposed by Thomas and Lipsky chemo-attraction of dendritic cells (DC) and/or the transformation of synoviocytes to follicular DC may play a key role in this process. In our model a so-called amplifier gene stimulates this chemo-attraction of and/or the differentiation to DC’s. The DC’s present self-peptides not to disease-inducing but to regulatory auto-reactive T cells that have been recruited also to the inflamed synovium. These regulatory T cells recognise self-peptides such as DERAA peptides from the HV III region of certain HLA-DR alleles presented by DR or DQ molecules. This DC-regulatory T cell interaction is an essential checkpoint for the control of the inflammation and is controlled by HLA class II genes. In the absence of protective HLA alleles and therefore self-reactive regulatory T cells this checkpoint fails and this results in a local loss of tolerance and a (severe) chronic arthritis (RA). This model has several important implications for the immunotherapy of RA: We may stop the search for a unique target antigen for disease-inducing T cells Immunotherapy that is exclusively targeted at T cells may have an adverse effect Immunotherapy strategies for RA should either be targeted at the re-establishment of a normal phenotype in synoviocytes or on restoring a functional immunoregulatory loop.

To evaluate the contributions of HLA-DQ and -DR polymorphisms to susceptibility to rheumatoid arthritis (RA) in a population in southern Spain, and to compare the value of the shared epitope (SE) and RA protection (RAP) models in accounting for the HLA class II region's contribution to RA predisposition.One hundred sixty RA patients and 153 healthy controls were typed for HLA-DRB1 and -DQB1 using high-resolution DNA techniques. Distributions of predisposing DRB1 alleles in patients and control subjects according to the SE model were compared with distributions of predisposing DQ and protective DERAA-positive DRBI alleles according to the RAP model.DQ3 (DQBI*03 and *04 combined with DQA1*03) and DQ5 (DQB1*0501/DQA1*0101) alleles predisposed individuals to RA independently of SE-positive DRB1 alleles. DQ3/3-homozygous individuals had the strongest risk of developing RA. DQ3 molecules predisposed to RA more than did DQ5 molecules. The weaker predisposition mediated by DQ5 included the DRB1*1001-carrying haplotype; no DRB1*1001-homozygous patients were observed. DRBI*0401 played a unique role in the contribution of DQ3-DR4 haplotypes to RA, in spite of its low frequency in southern Spain.The low prevalences of RA and of mild disease observed in Spain, and in southern Europe in general, can be explained in great part by the low frequency of DQ3-DR4 haplotypes, especially those carrying DRB1*0401. However, the overall distribution of HLA-DQ and -DR alleles in RA patients compared with control subjects is similar to that in other European and North American populations. A model involving both DQ and DR can best account for the contribution of HLA to RA.

We have reviewed the literature on the association of HLA class II with rheumatoid arthritis (RA). Strong linkage disequilibrium among DQB1, DQA1 and DRB1 alleles makes it difficult to evaluate the individual contribution of each locus. Nonetheless, there is a strong case for the role of DQB1*03 and *04 combined with DQA1*03 in susceptibility to severe RA while DQB1*0501 combined with DQA1*0101 and *0104 weakly predisposes to a mild form of RA. However, it is also clear that DRB1*0401 has a particular role in predisposition to the most severe form of the disease while other DRB1 alleles might provide protection. We would like to propose that in RA, as in type I diabetes, both DQ and DR loci contribute to predisposition to the disease.

Differences in allelic distribution at loci surrounding the human HLA-DRB1 and tumor necrosis factor (TNF) genes have been observed in association with systemic lupus erythematosus (SLE). We investigated whether the association of HLA-DRB1*0301 (HLA-DR3) and TNF-308A with SLE could be attributed to polymorphic markers in the chromosomal region encompassed by HLA-DRB1 and HLA-C. Ninety-one consecutive Caucasian patients with SLE and 253 controls (organ donors) were typed for HLA-DRB1, microsatellites D6S1014, D6S273, TNFa, MIB, C1_2_5, and C1_3_2 and the single nucleotide polymorphism at position -308 in the promoter of TNF. The independent contribution of alleles to disease susceptibility was estimated by cross-tabulation and multivariate logistic regression. Possession of TNF-308A was associated with susceptibility to SLE (odds ratio [95% confidence interval], 3.70 [2.24-6.11]). This remained present after stratification on possession of HLA-DR3 (pooled odds ratio, 2.53 [1.37-4.70]). Stratification revealed a possible association of possession of C1_2_5*192 with protection from SLE beyond the effects of HLA-DR3 and TNF-308A. A gene dosage effect was observed for -308A only (homozygotes, 7.75 [3.01-20.0], heterozygotes, 3.15 [1.85-5.37]). In multivariate analysis, possession of HLA-DR3, TNF-308A, and C1_2_5*192 remained independently associated with susceptibility to SLE (2.58 [1.29-5.18], 2.76 [1.43-5.31], and 0.26 [0.10-0.66], respectively). The association of possession of TNF-308A with susceptibility to SLE cannot be attributed to linkage to HLA-DR3 alone, nor to other polymorphic markers in the vicinity of the TNF gene. Further loci that are independently associated with SLE might be in the vicinity of marker C1_2_5.

HLA class II antigens influence disease progression as measured by extend of joint destruction in RA. This effect is supposed to be caused by formation of autoreactive T-cells after presentation of (auto)antigens in the context of HLA class II. To investigate whether in patients with recent-onset RA early DMARD treatment could prevent the involvement of autoreactive T cells, we analyzed the association of HLA class II and joint damage in 110 patients with early RA that were treated according to the pyramid strategy with DMARDs and 98 patients with early RA that were promptly treated with DMARDs at two weeks after the first visit.

The use of telemedicine appears particularly promising in cardiovascular diseases; it may reduce the decisional time during an acute myocardial infarction, which is the greater part of the so-called "avoidable delay" and the inappropriate admission to the Emergency Department with the possibility of ruling out an acute pathology. The aim of our study was to show the diagnostic accuracy of a telecardiology service in the daily activity of general practitioners.From February 1998 to February 1999, 150 general practitioners received a portable electrocardiographer (Card-Guard 7100) transferring, by a mobile or fixed telephone, a 12-lead ECG to a receiving station, where a cardiologist was available for the reporting and interactive teleconsultation.During 1 year 3456 calls took place. At the time of the ECG recording 44% of patients were symptomatic. Chest pain was present in 669 patients (44%), dyspnea in 21%, palpitation in 18%, dizziness in 7%, and asthenia in 13%. ECG and teleconsultation solved all the problems for 2452 patients (71%) and further diagnostic tests were requested in 862 patients (25%); 142 patients (4%) were sent to the Emergency Department. Cardiological diagnosis was confirmed in 95 patients (73%), while anxiety or gastritis were presumed in 35 patients (27%). In the group of patients (n = 3314) for whom the cardiologist solved the problem without admission to the Emergency Department, there were 5 patients who were admitted to the Emergency Department for myocardial ischemia in the following 48 hours after the teleconsultation. Telecardiology service showed versus Emergency Department admission a sensitivity of 95%, a specificity of 97.5%, and a diagnostic accuracy of 92.5%.These data confirm a good diagnostic value to the service and a useful support to the general practitioners' activity.

To evaluate the respective contributions of tumor necrosis factor (TNF) promoter polymorphisms and HLA-DR alleles to susceptibility to systemic lupus erythematosus (SLE).TNF-238G/A and 308G/A promoter polymorphisms and HLA-DRB1 alleles were determined in 99 consecutive Caucasian SLE patients and 177 Caucasian controls. Standard and Mantel-Haenszel odds ratios were calculated to assess the magnitude of the susceptibility factors. The presence or absence of the SLE classification criteria was determined and correlated with the TNF promoter and HLA-DRB1 genotypes.The frequency of the TNF-308A/A and 308G/A genotypes was significantly higher in SLE patients (odds ratio 5.0). Conversely, TNF-238G/A and 238A/A genotypes were equally prevalent in SLE patients and controls. The HLA-DR3 specificity (DRBI*0301 allele) was significantly more prevalent in the SLE population (odds ratio 4.4). Stratification to correct for interdependence of the 2 loci confirmed the association of both TNF-308A and HLA-DR3 with SLE (Mantel-Haenszel odds ratio 3.2 and 2.4, respectively). No correlation was found between TNF promoter and HLA-DRB1 genotypes and any SLE classification criterion or disease manifestation.TNF-308A and HLA-DR3 alleles are independent susceptibility factors for SLE.

Cardiovascular diseases are the leading cause of morbidity and mortality in Western countries and represent, in terms of diagnostic and treatment measures, a large amount of health care expenses. A telecardiology service may offer to general practitioners, in real time, a useful diagnostic tool and the possibility of an accurate screening of patients with suspected ischemic heart disease.From February to July 1998, in the provinces of Bergamo and Brescia (Italy), 178 general practitioners received a portable Card Guard 7100 electrocardiographer transferring, by a mobile or fixed telephone, a 12 lead ECG to a receiving station, where a cardiologist was available for the reporting and interactive teleconsultation.During the first 6 months a total 2800 calls took place. Due to incompleteness of requested data only 2254 traces, corresponding to 2254 subjects (mean age 63 +/- 18 years) were entered in the study. In 27% of patients (n = 609) there was a history of systemic hypertension, in 12.5% (n = 283) there was a history of coronary artery disease, and in 38% (n = 834) there was no history of cardiovascular diseases. At the time of ECG recording, 42% of patients (n = 949) were symptomatic: more common symptoms were chest pain (39%), dyspnea (23%), palpitation (19%), dizziness or faint (10%), and asthenia (9%). No action was suggested by cardiologists in 74% of cases. Of the remaining patients, 16% (n = 92) were referred to the Emergency Department, 27% (n = 158) were offered further diagnostic tests as an out patient, and 56% (n = 328) were started on medication or had their treatment changed.A telecardiology system provides a useful support to general practitioners in the management, in real time, of patients with cardiovascular conditions, and possibly contributes to optimization of health care costs in terms of appropriateness of hospital admissions and diagnostic tests.

Autonomic dysfunction seems to be involved in the progression and prognosis of congestive heart failure. Measurement of heart rate variability (HRV) provides a noninvasive method to obtain reliable and reproducible information on autonomic modulation of heart rate, but there is a difficulty in using HRV as a quantitative estimate of autonomic dysfunction in heart failure. This study was aimed at testing the hypothesis that abnormal modulation of heart rate assessed by power spectrum analysis may be present also in asymptomatic patients with left ventricular dysfunction and progress in patients with overt symptoms of congestive heart failure. HRV was measured in three groups of subjects: Group 1: 30 patients with chronic heart failure; Group 2: 21 patients with asymptomatic left ventricular dysfunction; and Group 3: 25 healthy volunteers as control group. HRV was evaluated by autoregressive spectral analysis with 600-beat ECG samples, while subjects were quietly recumbent (BSI), in conditions of controlled breathing (15 acts/min) (RSC) and passive orthostatism after tilting (80 degrees) (TLT). Patients in group 1 showed a reduction in the standard deviation of the R-R intervals (SDRR) (p0.0003) and in the low frequency component (LF) (p0.0001) compared to normal subjects. Low frequency component was not detectable in 11 patients of group I (p0.0008). On RSC and TLT, group 1 failed to show any modification in the low frequency and high frequency components (HF) under any stimulation. Group 2 showed no modification at baseline evaluation, no increase in the high frequency component on RSC and in LF during TLT compared to controls (p0.01 and p0.0001 respectively). At baseline, group 1 had a lower SDRR (p0.03) and LF (p0.0001) vs. group 2, whereas during stimulation the two groups exhibited the same behaviour. In conclusion, reduced heart rate variability is specific for both asymptomatic and symptomatic post-ischemic left ventricular dysfunction. Our results suggest that frequency domain analysis of heart rate variability during a stimulation test allows a more accurate definition of the degree of autonomic control of heart rate.

Collagen-induced arthritis (CIA) is an animal model of auto-immune inflammatory polyarthritis which has features similar to rheumatoid arthritis (RA). Much like RA, susceptibility to mouse CIA is influenced by the major histocompatibility complex (MHC) and is restricted to the H2 haplotypes q and r. In previous experiments, we have found that the introduction of an H2-Ebd transgene in H2-Aq CIA-susceptible mice was able to protect these mice against disease development. More recently, we have proposed that the polymorphism of the first domain of the Ebeta molecule modulates this protection, and that the presentation of a peptide from the third hypervariable region of the Ebeta chain by the H2-Aq molecule plays an important role in this mechanism. In the present report, we investigated whether the H2-E-mediated protection is H2-Aq-specific and whether the source of collagen has any influence. While the source of collagen had no effect on the protection, our results showed that the H2-E molecule failed to protect B10.RIII (H2(r)) mice against CIA. Further, the H2 haplotype r exerted a negative effect on the Ebetad-mediated protection in H2-Aq-restricted disease. Our results provide additional proof that self-MHC-derived peptides, such as Ebeta peptides, may play an important role in the T-cell repertoire education and/or modulation of the T-cell response in the periphery.

In ICD patients thrombo-embolic events (TEEs) are described as possible complications at implant or during the follow-up. We report four cases of TEEs (two peripheral and two cerebral; 6.5% of patients) that occurred in our series during a mean follow-up of 19.4 months. The patients had chronic postinfarction LV aneurysm (3) and idiopathic dilated cardiomyopathy (1). None had previous embolisms nor evidence of left atrial or LV clots at standard preoperative transthoracic echocardiography. No paroxysms of atrial fibrillation were documented prior or after ICD implant. We discuss the possible causes of embolization and the suitability of anticoagulant therapy in ICD patients.