Francesco Saccardo - Academia.edu (original) (raw)
Papers by Francesco Saccardo
Annals of the Rheumatic Diseases, 2013
Background the preliminary Classification Criteria for cryoglobulinemic vasculitis (CV) have been... more Background the preliminary Classification Criteria for cryoglobulinemic vasculitis (CV) have been developed in 2011 by an European cooperative study (1). Objectives to validate these Classification Criteria for CV with the participation of non-European Countries. Methods 20 Centres from Europe, Egypt, and Japan partecipated. New consecutive, unselected patients with CV (Group A) and controls (subjects with cryoglobulins without a CV based on the golden standard clinical judgment; Group B) were studied. A sample size of 140 patients for each group was estimated to obtain a sensitivity (SE) and a specificity (SP) of at least 90±5%, according to the previous results (1). A dedicated chart was distributed to the Centres. The sensitivity and specificity of the 2011 Classification Criteria were calculated in the present validation series by comparing Group A versus Group B. Results 251 patients in Group A and 175 controls in Group B were recruited. The questionnaire (at least 2/3 positive answers) showed a SE of 89.2% (95% CI 85.4-93.1) and a SP of 93.7% (95% CI 90.1-97.3); the clinical item (at least 3/4 clinical items among constitutional, articular, vascular and neurologic involvement) showed a SE of 76.1% (95% CI 70.8-81.4) and a SP of 88.6% (95% CI 83.8-93.9), and the laboratory item (at least 2/3 tests, among positive rheumatoid factor, low C4, and the presence of serum monoclonal component) showed 75.1% (95% CI 69.5-80.7) of SE and 71.5% (95% CI 64.6-78.4) of SP. The final 2011 Classification Criteria (at least 2/3 positive items) showed a SE of 89.3% (95% CI 85.3-93.3) and a SP of 93.9 % (95% CI 90.3-97.6). Conclusions: Conclusion : The 2011 International Classification Criteria for the cryoglobulinemic vasculitis have been validated in a new cohort of real cases and controls. Patients where CV is suspected on clinical grounds, but where cryoglobulins are negative, cannot be classified, since positive serum cryoglobulinemia is a conditio sine qua non for classification (1). However, the performance of these criteria on this subset of patients is under evaluation. References De Vita S, et al. Ann Rheum Dis 2011;70:1183-90. Disclosure of Interest None Declared
Autoimmunity Reviews, 2011
Objective: The objective of this review was to define a core set of recommendations for the treat... more Objective: The objective of this review was to define a core set of recommendations for the treatment of HCVassociated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion. Methods: Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements. Results: An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild-moderate HCV-related MCS. Prolonged treatment (up to 72 weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low-medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild-moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A low-antigencontent diet can be considered as supportive treatment in all symptomatic MCS patients. Although there are no data from controlled trials, controlling pain should always be attempted by tailoring the treatment to individual patients on the basis of the guidelines used in other vasculitides. Conclusion: Although there are few controlled randomised trials of MCS treatment, increasing knowledge of its pathogenesis is opening up new frontiers. The recommendations provided may be useful as provisional guidelines for the management of MCS.
Horttechnology, Oct 1, 2005
ADDITIONAL INDEX WORDS. Cynara cardunculus var. scolymus, offshoot, soilless, benzylaminopurine, ... more ADDITIONAL INDEX WORDS. Cynara cardunculus var. scolymus, offshoot, soilless, benzylaminopurine, cold storage, rooting SUMMARY. A research project was conducted at the University of Tuscia, Viterbo (central Italy), to set up a vegetative propagation system for producing diseasefree artichoke transplants (Cynara cardunculus var. scolymus) of the Romanesco type (cultivar C3). The system included the following steps: 1) micropropagated plantlets were grown in a soilless culture year-round in greenhouse conditions, starting at the end of August; 2) stock plants were periodically treated with a chemical growth regulator [6-benzylamino purine (BA)] and then cut back at the collar level to promote offshoot production; 3) offshoots were periodically harvested and cold stored; and 4) cuttings were rooted at the end of spring under conditions of high humidity in multi-pack trays so as to be ready for summer transplanting. Results showed that the foliar application of BA to the stock plants increased the offshoot number quadratically to 200 mg·L -1 . The rooting percentages of cuttings and root growth were enhanced by raising the cutting weight class (30-45 g) and by the application of naphthaleneacetic acid (NAA) to the cutting root zone at a rate of 2000 mg·L -1 . The percent rotten cuttings increased as the 2 °C cold-storage time increased from 30 to 150 days. Similarly, the percentage of rooting and root growth decreased approximately from 60 to 150 days.
HortTechnology
ADDITIONAL INDEX WORDS. Cynara cardunculus var. scolymus, offshoot, soilless, benzylaminopurine, ... more ADDITIONAL INDEX WORDS. Cynara cardunculus var. scolymus, offshoot, soilless, benzylaminopurine, cold storage, rooting SUMMARY. A research project was conducted at the University of Tuscia, Viterbo (central Italy), to set up a vegetative propagation system for producing diseasefree artichoke transplants (Cynara cardunculus var. scolymus) of the Romanesco type (cultivar C3). The system included the following steps: 1) micropropagated plantlets were grown in a soilless culture year-round in greenhouse conditions, starting at the end of August; 2) stock plants were periodically treated with a chemical growth regulator [6-benzylamino purine (BA)] and then cut back at the collar level to promote offshoot production; 3) offshoots were periodically harvested and cold stored; and 4) cuttings were rooted at the end of spring under conditions of high humidity in multi-pack trays so as to be ready for summer transplanting. Results showed that the foliar application of BA to the stock plants increased the offshoot number quadratically to 200 mg·L -1 . The rooting percentages of cuttings and root growth were enhanced by raising the cutting weight class (30-45 g) and by the application of naphthaleneacetic acid (NAA) to the cutting root zone at a rate of 2000 mg·L -1 . The percent rotten cuttings increased as the 2 °C cold-storage time increased from 30 to 150 days. Similarly, the percentage of rooting and root growth decreased approximately from 60 to 150 days.
La Ricerca in Clinica e in Laboratorio
The clinical and immunochemical classification of 376 patients with cryoglobulinemia is presented... more The clinical and immunochemical classification of 376 patients with cryoglobulinemia is presented. In 141 cases (37.5%) the syndrome was considered idiopathic. Among the secondary forms, chronic liver diseases and connective tissue diseases shared most frequently mixed cryoglobulins (18.8 and 15.4% of cases, respectively). Another common association was that with Waldenström's macroglobulinemia: cryoglobulins were found in 20% of these patients. In 5 patients (2 with the essential form and 3 with cryoglobulinemia secondary to Waldenström's disease) a Cl-inhibitor deficiency was discovered; the complement profile was characteristic of the acquired type and episodes of angioedema occurred. Studying the clinical course of 71 cases of essential mixed cryoglobulinemia followed-up for 4-20 years we concluded that the evolution of type II and type III cryoglobulinemias is different because that of type II seems to have a more severe course and may differentiate in a lymphoproliferative disorder; the immunochemical type of cryoglobulins seems therefore to have a prognostic significance. Because of the considerable overlap in the distribution of immunochemical types among the clinical subsets, a mixed classification (both biochemical and clinical) is proposed.
La Ricerca in Clinica e in Laboratorio
La Ricerca in Clinica e in Laboratorio
QJM: monthly journal of the Association of Physicians
In a multi-centre retrospective study, we compared clinical and laboratory data in 913 patients w... more In a multi-centre retrospective study, we compared clinical and laboratory data in 913 patients with cryoglobulinaemias, divided as: (i) essential cryoglobulinaemias; (ii) cryoglobulinaemias secondary to connective tissue diseases (CTD), lymphoproliferative or other haematological diseases (LPD), chronic liver diseases (CLD), and 'other diseases'. Purpura was the commonest presenting feature in all groups and was more common in essential cryoglobulinaemias (p < 0.0001). Meltzer's triad (purpura, arthralgia, weakness) was less frequent, but similarly distributed. Renal involvement was randomly distributed. Neurological impairment was less frequent in cryoglobulinaemias secondary to CLD (p < 0.002). Raynaud's phenomenon, arthritis and sicca syndrome were more frequent in cryoglobulinaemias secondary to CTD. Essential cryoglobulinaemias had a significantly higher percentage of serum complement C4 < 8 mg/dl (p < 0.004), of detectable rheumatoid factor activity (p < 0.0002), and of type II cryoglobulins (p < 0.0001). Liver involvement was evident at presentation in 32.6% of essential cryoglobulinaemias, 27.1% of cryoglobulinaemias secondary to LPD and 12.2% of cryoglobulinaemias secondary to CTD. Antibodies to hepatitis B surface (HBsAg) and core (HBc) antigens were more frequent in cryoglobulinaemias secondary to CLD; anti-HBs antibodies were randomly distributed. Antibodies to hepatitis C (HCV) were tested for in 224 patients, and prevalence was high in all the groups, but lower in cryoglobulinaemias secondary to CTD (p < 0.0001). Type II and type III essential cryoglobulinaemias differed significantly in renal involvement (p < 0.0001), cryocrit > 3% (p < 0.0001), C4 < 15 mg/dl (p < 0.001), HBsAg prevalence (p < 0.01) and purpura (p < 0.05). Despite the high prevalence of HCV markers in all groups, the role of HCV in essential cryoglobulinaemia is not well defined; HBV seems to play only a marginal role.
Clinical and experimental rheumatology
The association of the hepatitis C virus (HCV) with the cryoglobulinemic syndrome is well known, ... more The association of the hepatitis C virus (HCV) with the cryoglobulinemic syndrome is well known, but its pathogenetic mechanism still remains to be clarified. HCV-RNA has been found in the peripheral blood mononuclear cells (PBMC) of infected subjects. We investigated the presence of the HCV genome in bone marrow cells (BMC), and the distribution of different HCV genotypes in individuals with mixed cryoglobulinemia (MC) and in noncryoglobulinemic controls. 15 anti-HCV positive subjects with MC, 7 non-cryoglobulinemic patients with type C chronic active hepatitis (CAH) and 2 anti-HCV negative controls were studied. HCV-RNA was detected by nested PCR of the highly conserved 5'-NCR sequence. HCV typing was carried out by means of the hybridization of the same amplified region with specific probes. HCV-RNA was present in the PBMC of a large proportion of the MC patients and controls without any significant differences. On the contrary, HCV-RNA was present in the bone marrow cells of all the patients with MC and in 43% of the CAH controls. The HCV 1b and 2a genotypes seem to be the most prevalent among MC patients. Nevertheless, the patients with type II MC had a very high prevalence of the 2a genotype (77%). The results suggest that the presence of HCV-RNA in bone marrow cells may be correlated to the pathogenetic mechanism of MC. Other studies are needed to confirm the frequent association of HCV genotype 2 with MC.
Clinical and experimental rheumatology
The aim of the present study is to provide information on clinical outcome of the patients affect... more The aim of the present study is to provide information on clinical outcome of the patients affected by HCV-positive mixed cryoglobulinemia (MC) treated with PEG-IFN and Ribavirin for 6 or 12 months according to the HCV genotype. Eighty-six patients (42 women and 44 men) were enrolled in 8 Italian centres. All the patients had MC in the active phase of the disease. The patients received Peginterferon alfa-2b 1.5 mcg/kg/once a week (QW) and daily oral Ribavirin (800/1,000/1,200) according to their body weight for 48 weeks for genotype 1 and 4 and for 24 weeks for genotypes 2 and 3. In the 44 patients who underwent 12 months of therapy, 17 cases (39%) could be considered as 'non-responders' and 11 relapsed, therefore only 16 patients (36%) obtained a sustained virological response. In the 42 patients who underwent six months of therapy only 7 cases (17%) could be considered as 'non-responders' and 8 relapsed, therefore 27 patients (64%) obtained a sustained virological ...
Journal of Autoimmunity, 2015
To evaluate the efficacy and safety in the long term of a retreatment regimen with Rituximab (RTX... more To evaluate the efficacy and safety in the long term of a retreatment regimen with Rituximab (RTX) alone administered at clinical relapse in cryoglobulinemic vasculitis (CV). Thirty patients with severe HCV-related CV, previously enrolled in the multicentre Italian trial on RTX in the treatment of CV, were retrospectively evaluated after the end of the trial. All of them were managed with RTX alone at clinical relapse, if any. Disease activity at the last available follow up was defined as complete remission (absence of active disease), partial remission (response &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 50% of at least one manifestation among glomerulonephritis, peripheral neuropathy or skin ulcers) or active disease. The mean follow up after the first RTX cycle was 72.6 (20.4) months. After the end of the trial, 21/30 (70%) patients showed an active follow up [81.7 (10.9) months)], 3/30 (10%) lost follow up and 6/30 (20%) died. 12/21 (57.1%) patients were in complete disease remission, 5/21 (23.8%) showed a partial response and 4/21 (19%) had an active disease. 17/30 (56.7%) patients needed retreatment for relapse with a mean time to retreatment of 22.3 (12.1) months. Treatment survival of this regimen was 7.6 (0.3) years. Recurrent non-severe infections occurred in 3/30, with chronic hypogammaglobulinemia in 2/3 patients. A long-term regimen of retreatment with RTX alone given at clinical relapse seems to be effective and safe in CV, with a low rate of infections and severe hypogammaglobulinemia.
Journal of the European Academy of Dermatology and Venereology
Annali italiani di medicina interna : organo ufficiale della Società italiana di medicina interna
We discuss the cases of two patients affected with chronic eosinophilic pneumonia (CEP) pleurisy ... more We discuss the cases of two patients affected with chronic eosinophilic pneumonia (CEP) pleurisy and eosinophilia in pleural effusion, not previously mentioned in the literature, to point out their peculiarity, to consider differential diagnosis and the effect of steroid therapy. Both patients, a 57-year-old man and a 55-year-old woman, were atopic: they had been suffering from allergic rhinitis and asthma for several years when they suffered sudden onset of cough, dyspnea and thoracic pain. This symptomatology persisted for more than 6 weeks. Chest radiography highlighted pulmonary infiltrates, not fixed in the first case, fixed in the second. The laboratory features revealed eosinophilia in peripheral blood and in pleural effusion. These data conformed to the criteria suggested by Jederlinic et al. for the diagnosis of chronic eosinophilic pneumonia. Tuberculosis had been present in the remote history of the second case; the repeated research for mycobacteria was negative, and no ...
Clinical and experimental rheumatology
The best treatment for cryoglobulinemic syndrome (CS) is still an unsolved problem. Recently colc... more The best treatment for cryoglobulinemic syndrome (CS) is still an unsolved problem. Recently colchicine has been successfully used to treat vasculitides and other immune-mediated diseases. Therefore, we undertook to treat 17 CS patients with colchicine (1 mg/day for 6-48 months), 8 of them with essential mixed cryoglobulinemia (EMC) and 9 with CS secondary to liver disease. In all patients the clinical and laboratory features were evaluated at the beginning of the study and during the first 6-12 months; 10 cases were followed for a longer period (18-48 months). During the first period symptoms improved as follows: purpura in 15 of 17 patients, weakness in 9 of 14 and leg ulcers in 3 of 5. Hepatic and renal function tests, hypocomplementemia, rheumatoid factor (RF) titres and the cryocrit also improved. Prolonged follow-up showed a relapse in the different variables, although they remained at better levels than at the beginning. Only the cryocrit showed a further reduction. Though th...
Clinical and experimental rheumatology
We investigated the presence of anti-GOR antibodies in patients with essential mixed cryoglobulin... more We investigated the presence of anti-GOR antibodies in patients with essential mixed cryoglobulinemia, since both autoimmune pathogenetic processes and a high prevalence of HCV infection are present in this syndrome. We compared these cases to patients with HCV-related chronic active hepatitis or alcoholism, and to ex-blood donors. A total of 60 patients with biopsy-proven chronic liver disease were studied. HCV related markers, cryoglobulins, anti-GOR antibodies and ANA were detected in all of the groups. Our data would appear to indicate that anti-GOR are related to the presence of HCV chronic hepatitis and not to cryoglobulinemia or chronic liver damage.
Clinical and experimental rheumatology
The cryoglobulinemic syndrome (CS) may be associated with other diseases; when it is not, it is t... more The cryoglobulinemic syndrome (CS) may be associated with other diseases; when it is not, it is termed essential. Recently the natural history of this disease has been re-evaluated on the basis of its close association with HCV markers. In this context, the GISC has studied a large series of patients from several Italian centres. In a multicentric retrospective study of 913 cases, we evaluated the clinical and laboratory signs at onset in patients with essential mixed cryoglobulinemias (EMC) (654 cases) or secondary cryoglobulinemias (SC) (259 cases) and sought to define possible diagnostic criteria typical of the different CS. We also carried out a retrospective 5-year cohort study on 192 patients selected randomly from the 913 cases described above. In particular, we examined the correlation between the presence/absence of concomitant diseases and the presence of HCV markers on the clinical evolution and survival of the patients. Purpura, rheumatoid factors (RF), significant C4 co...
La Ricerca in clinica e in laboratorio
Ninety-three patients with essential mixed cryoglobulinemia have been followed for more than 5 ye... more Ninety-three patients with essential mixed cryoglobulinemia have been followed for more than 5 years in 75% of cases; 21 patients died during this period and the mean age at death was 54 years. The most common cause of death was renal failure. The percentages of patients who survived after 5 and 10 years from the diagnosis were 87 and 74%, respectively. The cryoglobulin type seems to be an important prognostic factor: in our population the type II/III ratio is 6/7 at diagnosis, while it becomes 2/1 when the patients who died are considered.
La Ricerca in clinica e in laboratorio
A panel of autoantibodies has been tested in serum samples and cryoprecipitates of 14 patients af... more A panel of autoantibodies has been tested in serum samples and cryoprecipitates of 14 patients affected by essential mixed cryoglobulinemia (EMC) as well as in 12 subjects with secondary non-lupoid cryoglobulinemia (SC). Three out of 14 patients affected by EMC were ANA-positive (2 at 1:40 dilution and one at 1:80 dilution). Two out of 12 patients with SC were ANA-positive (both at 1:40 dilution). No autoantibodies were found in the cryoprecipitates. These data seem to confirm some previous observations and do not indicate a role of autoantibodies in the cryoprecipitate formation.
La Ricerca in clinica e in laboratorio
T lymphocyte subpopulations defined by monoclonal antibodies were determined in patients with ess... more T lymphocyte subpopulations defined by monoclonal antibodies were determined in patients with essential mixed cryoglobulinemia (EMC) and secondary cryoglobulinemias (SC). A decrease of circulating lymphocytes and a reduction in the absolute number of T3+, T4+ and T8+ (p less than 0.01) as well as in the percentage of T4+ lymphocytes (p less than 0.05) were found in EMC. A significant decrease of T8+ cells, both in percentage (p less than 0.01) and absolute number (p less than 0.001), was evidenced in SC, while T3+ and T4+ cell counts were not significantly different from those of healthy controls.
La Ricerca in clinica e in laboratorio
The clinical and immunochemical classification of 376 patients with cryoglobulinemia is presented... more The clinical and immunochemical classification of 376 patients with cryoglobulinemia is presented. In 141 cases (37.5%) the syndrome was considered idiopathic. Among the secondary forms, chronic liver diseases and connective tissue diseases shared most frequently mixed cryoglobulins (18.8 and 15.4% of cases, respectively). Another common association was that with Waldenström's macroglobulinemia: cryoglobulins were found in 20% of these patients. In 5 patients (2 with the essential form and 3 with cryoglobulinemia secondary to Waldenström's disease) a Cl-inhibitor deficiency was discovered; the complement profile was characteristic of the acquired type and episodes of angioedema occurred. Studying the clinical course of 71 cases of essential mixed cryoglobulinemia followed-up for 4-20 years we concluded that the evolution of type II and type III cryoglobulinemias is different because that of type II seems to have a more severe course and may differentiate in a lymphoprolifera...
Annals of the Rheumatic Diseases, 2013
Background the preliminary Classification Criteria for cryoglobulinemic vasculitis (CV) have been... more Background the preliminary Classification Criteria for cryoglobulinemic vasculitis (CV) have been developed in 2011 by an European cooperative study (1). Objectives to validate these Classification Criteria for CV with the participation of non-European Countries. Methods 20 Centres from Europe, Egypt, and Japan partecipated. New consecutive, unselected patients with CV (Group A) and controls (subjects with cryoglobulins without a CV based on the golden standard clinical judgment; Group B) were studied. A sample size of 140 patients for each group was estimated to obtain a sensitivity (SE) and a specificity (SP) of at least 90±5%, according to the previous results (1). A dedicated chart was distributed to the Centres. The sensitivity and specificity of the 2011 Classification Criteria were calculated in the present validation series by comparing Group A versus Group B. Results 251 patients in Group A and 175 controls in Group B were recruited. The questionnaire (at least 2/3 positive answers) showed a SE of 89.2% (95% CI 85.4-93.1) and a SP of 93.7% (95% CI 90.1-97.3); the clinical item (at least 3/4 clinical items among constitutional, articular, vascular and neurologic involvement) showed a SE of 76.1% (95% CI 70.8-81.4) and a SP of 88.6% (95% CI 83.8-93.9), and the laboratory item (at least 2/3 tests, among positive rheumatoid factor, low C4, and the presence of serum monoclonal component) showed 75.1% (95% CI 69.5-80.7) of SE and 71.5% (95% CI 64.6-78.4) of SP. The final 2011 Classification Criteria (at least 2/3 positive items) showed a SE of 89.3% (95% CI 85.3-93.3) and a SP of 93.9 % (95% CI 90.3-97.6). Conclusions: Conclusion : The 2011 International Classification Criteria for the cryoglobulinemic vasculitis have been validated in a new cohort of real cases and controls. Patients where CV is suspected on clinical grounds, but where cryoglobulins are negative, cannot be classified, since positive serum cryoglobulinemia is a conditio sine qua non for classification (1). However, the performance of these criteria on this subset of patients is under evaluation. References De Vita S, et al. Ann Rheum Dis 2011;70:1183-90. Disclosure of Interest None Declared
Autoimmunity Reviews, 2011
Objective: The objective of this review was to define a core set of recommendations for the treat... more Objective: The objective of this review was to define a core set of recommendations for the treatment of HCVassociated mixed cryoglobulinemia syndrome (MCS) by combining current evidence from clinical trials and expert opinion. Methods: Expert physicians involved in studying and treating patients with MCS formulated statements after discussing the published data. Their attitudes to treatment approaches (particularly those insufficiently supported by published data) were collected before the consensus conference by means of a questionnaire, and were considered when formulating the statements. Results: An attempt at viral eradication using pegylated interferon plus ribavirin should be considered the first-line therapeutic option in patients with mild-moderate HCV-related MCS. Prolonged treatment (up to 72 weeks) may be considered in the case of virological non-responders showing clinical and laboratory improvements. Rituximab (RTX) should be considered in patients with severe vasculitis and/or skin ulcers, peripheral neuropathy or glomerulonephritis. High-dose pulsed glucocorticoid (GC) therapy is useful in severe conditions and, when necessary, can be considered in combination with RTX; on the contrary, the majority of conference participants discouraged the chronic use of low-medium GC doses. Apheresis remains the elective treatment for severe, life-threatening hyper-viscosity syndrome; its use should be limited to patients who do not respond to (or who are ineligible for) other treatments, and emergency situations. Cyclophosphamide can be considered in combination with apheresis, but the data supporting its use are scarce. Despite the limited available data, colchicine is used by many of the conference participants, particularly in patients with mild-moderate MCS refractory to other therapies. Careful monitoring of the side effects of each drug, and its effects on HCV replication and liver function tests is essential. A low-antigencontent diet can be considered as supportive treatment in all symptomatic MCS patients. Although there are no data from controlled trials, controlling pain should always be attempted by tailoring the treatment to individual patients on the basis of the guidelines used in other vasculitides. Conclusion: Although there are few controlled randomised trials of MCS treatment, increasing knowledge of its pathogenesis is opening up new frontiers. The recommendations provided may be useful as provisional guidelines for the management of MCS.
Horttechnology, Oct 1, 2005
ADDITIONAL INDEX WORDS. Cynara cardunculus var. scolymus, offshoot, soilless, benzylaminopurine, ... more ADDITIONAL INDEX WORDS. Cynara cardunculus var. scolymus, offshoot, soilless, benzylaminopurine, cold storage, rooting SUMMARY. A research project was conducted at the University of Tuscia, Viterbo (central Italy), to set up a vegetative propagation system for producing diseasefree artichoke transplants (Cynara cardunculus var. scolymus) of the Romanesco type (cultivar C3). The system included the following steps: 1) micropropagated plantlets were grown in a soilless culture year-round in greenhouse conditions, starting at the end of August; 2) stock plants were periodically treated with a chemical growth regulator [6-benzylamino purine (BA)] and then cut back at the collar level to promote offshoot production; 3) offshoots were periodically harvested and cold stored; and 4) cuttings were rooted at the end of spring under conditions of high humidity in multi-pack trays so as to be ready for summer transplanting. Results showed that the foliar application of BA to the stock plants increased the offshoot number quadratically to 200 mg·L -1 . The rooting percentages of cuttings and root growth were enhanced by raising the cutting weight class (30-45 g) and by the application of naphthaleneacetic acid (NAA) to the cutting root zone at a rate of 2000 mg·L -1 . The percent rotten cuttings increased as the 2 °C cold-storage time increased from 30 to 150 days. Similarly, the percentage of rooting and root growth decreased approximately from 60 to 150 days.
HortTechnology
ADDITIONAL INDEX WORDS. Cynara cardunculus var. scolymus, offshoot, soilless, benzylaminopurine, ... more ADDITIONAL INDEX WORDS. Cynara cardunculus var. scolymus, offshoot, soilless, benzylaminopurine, cold storage, rooting SUMMARY. A research project was conducted at the University of Tuscia, Viterbo (central Italy), to set up a vegetative propagation system for producing diseasefree artichoke transplants (Cynara cardunculus var. scolymus) of the Romanesco type (cultivar C3). The system included the following steps: 1) micropropagated plantlets were grown in a soilless culture year-round in greenhouse conditions, starting at the end of August; 2) stock plants were periodically treated with a chemical growth regulator [6-benzylamino purine (BA)] and then cut back at the collar level to promote offshoot production; 3) offshoots were periodically harvested and cold stored; and 4) cuttings were rooted at the end of spring under conditions of high humidity in multi-pack trays so as to be ready for summer transplanting. Results showed that the foliar application of BA to the stock plants increased the offshoot number quadratically to 200 mg·L -1 . The rooting percentages of cuttings and root growth were enhanced by raising the cutting weight class (30-45 g) and by the application of naphthaleneacetic acid (NAA) to the cutting root zone at a rate of 2000 mg·L -1 . The percent rotten cuttings increased as the 2 °C cold-storage time increased from 30 to 150 days. Similarly, the percentage of rooting and root growth decreased approximately from 60 to 150 days.
La Ricerca in Clinica e in Laboratorio
The clinical and immunochemical classification of 376 patients with cryoglobulinemia is presented... more The clinical and immunochemical classification of 376 patients with cryoglobulinemia is presented. In 141 cases (37.5%) the syndrome was considered idiopathic. Among the secondary forms, chronic liver diseases and connective tissue diseases shared most frequently mixed cryoglobulins (18.8 and 15.4% of cases, respectively). Another common association was that with Waldenström's macroglobulinemia: cryoglobulins were found in 20% of these patients. In 5 patients (2 with the essential form and 3 with cryoglobulinemia secondary to Waldenström's disease) a Cl-inhibitor deficiency was discovered; the complement profile was characteristic of the acquired type and episodes of angioedema occurred. Studying the clinical course of 71 cases of essential mixed cryoglobulinemia followed-up for 4-20 years we concluded that the evolution of type II and type III cryoglobulinemias is different because that of type II seems to have a more severe course and may differentiate in a lymphoproliferative disorder; the immunochemical type of cryoglobulins seems therefore to have a prognostic significance. Because of the considerable overlap in the distribution of immunochemical types among the clinical subsets, a mixed classification (both biochemical and clinical) is proposed.
La Ricerca in Clinica e in Laboratorio
La Ricerca in Clinica e in Laboratorio
QJM: monthly journal of the Association of Physicians
In a multi-centre retrospective study, we compared clinical and laboratory data in 913 patients w... more In a multi-centre retrospective study, we compared clinical and laboratory data in 913 patients with cryoglobulinaemias, divided as: (i) essential cryoglobulinaemias; (ii) cryoglobulinaemias secondary to connective tissue diseases (CTD), lymphoproliferative or other haematological diseases (LPD), chronic liver diseases (CLD), and 'other diseases'. Purpura was the commonest presenting feature in all groups and was more common in essential cryoglobulinaemias (p < 0.0001). Meltzer's triad (purpura, arthralgia, weakness) was less frequent, but similarly distributed. Renal involvement was randomly distributed. Neurological impairment was less frequent in cryoglobulinaemias secondary to CLD (p < 0.002). Raynaud's phenomenon, arthritis and sicca syndrome were more frequent in cryoglobulinaemias secondary to CTD. Essential cryoglobulinaemias had a significantly higher percentage of serum complement C4 < 8 mg/dl (p < 0.004), of detectable rheumatoid factor activity (p < 0.0002), and of type II cryoglobulins (p < 0.0001). Liver involvement was evident at presentation in 32.6% of essential cryoglobulinaemias, 27.1% of cryoglobulinaemias secondary to LPD and 12.2% of cryoglobulinaemias secondary to CTD. Antibodies to hepatitis B surface (HBsAg) and core (HBc) antigens were more frequent in cryoglobulinaemias secondary to CLD; anti-HBs antibodies were randomly distributed. Antibodies to hepatitis C (HCV) were tested for in 224 patients, and prevalence was high in all the groups, but lower in cryoglobulinaemias secondary to CTD (p < 0.0001). Type II and type III essential cryoglobulinaemias differed significantly in renal involvement (p < 0.0001), cryocrit > 3% (p < 0.0001), C4 < 15 mg/dl (p < 0.001), HBsAg prevalence (p < 0.01) and purpura (p < 0.05). Despite the high prevalence of HCV markers in all groups, the role of HCV in essential cryoglobulinaemia is not well defined; HBV seems to play only a marginal role.
Clinical and experimental rheumatology
The association of the hepatitis C virus (HCV) with the cryoglobulinemic syndrome is well known, ... more The association of the hepatitis C virus (HCV) with the cryoglobulinemic syndrome is well known, but its pathogenetic mechanism still remains to be clarified. HCV-RNA has been found in the peripheral blood mononuclear cells (PBMC) of infected subjects. We investigated the presence of the HCV genome in bone marrow cells (BMC), and the distribution of different HCV genotypes in individuals with mixed cryoglobulinemia (MC) and in noncryoglobulinemic controls. 15 anti-HCV positive subjects with MC, 7 non-cryoglobulinemic patients with type C chronic active hepatitis (CAH) and 2 anti-HCV negative controls were studied. HCV-RNA was detected by nested PCR of the highly conserved 5'-NCR sequence. HCV typing was carried out by means of the hybridization of the same amplified region with specific probes. HCV-RNA was present in the PBMC of a large proportion of the MC patients and controls without any significant differences. On the contrary, HCV-RNA was present in the bone marrow cells of all the patients with MC and in 43% of the CAH controls. The HCV 1b and 2a genotypes seem to be the most prevalent among MC patients. Nevertheless, the patients with type II MC had a very high prevalence of the 2a genotype (77%). The results suggest that the presence of HCV-RNA in bone marrow cells may be correlated to the pathogenetic mechanism of MC. Other studies are needed to confirm the frequent association of HCV genotype 2 with MC.
Clinical and experimental rheumatology
The aim of the present study is to provide information on clinical outcome of the patients affect... more The aim of the present study is to provide information on clinical outcome of the patients affected by HCV-positive mixed cryoglobulinemia (MC) treated with PEG-IFN and Ribavirin for 6 or 12 months according to the HCV genotype. Eighty-six patients (42 women and 44 men) were enrolled in 8 Italian centres. All the patients had MC in the active phase of the disease. The patients received Peginterferon alfa-2b 1.5 mcg/kg/once a week (QW) and daily oral Ribavirin (800/1,000/1,200) according to their body weight for 48 weeks for genotype 1 and 4 and for 24 weeks for genotypes 2 and 3. In the 44 patients who underwent 12 months of therapy, 17 cases (39%) could be considered as 'non-responders' and 11 relapsed, therefore only 16 patients (36%) obtained a sustained virological response. In the 42 patients who underwent six months of therapy only 7 cases (17%) could be considered as 'non-responders' and 8 relapsed, therefore 27 patients (64%) obtained a sustained virological ...
Journal of Autoimmunity, 2015
To evaluate the efficacy and safety in the long term of a retreatment regimen with Rituximab (RTX... more To evaluate the efficacy and safety in the long term of a retreatment regimen with Rituximab (RTX) alone administered at clinical relapse in cryoglobulinemic vasculitis (CV). Thirty patients with severe HCV-related CV, previously enrolled in the multicentre Italian trial on RTX in the treatment of CV, were retrospectively evaluated after the end of the trial. All of them were managed with RTX alone at clinical relapse, if any. Disease activity at the last available follow up was defined as complete remission (absence of active disease), partial remission (response &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; 50% of at least one manifestation among glomerulonephritis, peripheral neuropathy or skin ulcers) or active disease. The mean follow up after the first RTX cycle was 72.6 (20.4) months. After the end of the trial, 21/30 (70%) patients showed an active follow up [81.7 (10.9) months)], 3/30 (10%) lost follow up and 6/30 (20%) died. 12/21 (57.1%) patients were in complete disease remission, 5/21 (23.8%) showed a partial response and 4/21 (19%) had an active disease. 17/30 (56.7%) patients needed retreatment for relapse with a mean time to retreatment of 22.3 (12.1) months. Treatment survival of this regimen was 7.6 (0.3) years. Recurrent non-severe infections occurred in 3/30, with chronic hypogammaglobulinemia in 2/3 patients. A long-term regimen of retreatment with RTX alone given at clinical relapse seems to be effective and safe in CV, with a low rate of infections and severe hypogammaglobulinemia.
Journal of the European Academy of Dermatology and Venereology
Annali italiani di medicina interna : organo ufficiale della Società italiana di medicina interna
We discuss the cases of two patients affected with chronic eosinophilic pneumonia (CEP) pleurisy ... more We discuss the cases of two patients affected with chronic eosinophilic pneumonia (CEP) pleurisy and eosinophilia in pleural effusion, not previously mentioned in the literature, to point out their peculiarity, to consider differential diagnosis and the effect of steroid therapy. Both patients, a 57-year-old man and a 55-year-old woman, were atopic: they had been suffering from allergic rhinitis and asthma for several years when they suffered sudden onset of cough, dyspnea and thoracic pain. This symptomatology persisted for more than 6 weeks. Chest radiography highlighted pulmonary infiltrates, not fixed in the first case, fixed in the second. The laboratory features revealed eosinophilia in peripheral blood and in pleural effusion. These data conformed to the criteria suggested by Jederlinic et al. for the diagnosis of chronic eosinophilic pneumonia. Tuberculosis had been present in the remote history of the second case; the repeated research for mycobacteria was negative, and no ...
Clinical and experimental rheumatology
The best treatment for cryoglobulinemic syndrome (CS) is still an unsolved problem. Recently colc... more The best treatment for cryoglobulinemic syndrome (CS) is still an unsolved problem. Recently colchicine has been successfully used to treat vasculitides and other immune-mediated diseases. Therefore, we undertook to treat 17 CS patients with colchicine (1 mg/day for 6-48 months), 8 of them with essential mixed cryoglobulinemia (EMC) and 9 with CS secondary to liver disease. In all patients the clinical and laboratory features were evaluated at the beginning of the study and during the first 6-12 months; 10 cases were followed for a longer period (18-48 months). During the first period symptoms improved as follows: purpura in 15 of 17 patients, weakness in 9 of 14 and leg ulcers in 3 of 5. Hepatic and renal function tests, hypocomplementemia, rheumatoid factor (RF) titres and the cryocrit also improved. Prolonged follow-up showed a relapse in the different variables, although they remained at better levels than at the beginning. Only the cryocrit showed a further reduction. Though th...
Clinical and experimental rheumatology
We investigated the presence of anti-GOR antibodies in patients with essential mixed cryoglobulin... more We investigated the presence of anti-GOR antibodies in patients with essential mixed cryoglobulinemia, since both autoimmune pathogenetic processes and a high prevalence of HCV infection are present in this syndrome. We compared these cases to patients with HCV-related chronic active hepatitis or alcoholism, and to ex-blood donors. A total of 60 patients with biopsy-proven chronic liver disease were studied. HCV related markers, cryoglobulins, anti-GOR antibodies and ANA were detected in all of the groups. Our data would appear to indicate that anti-GOR are related to the presence of HCV chronic hepatitis and not to cryoglobulinemia or chronic liver damage.
Clinical and experimental rheumatology
The cryoglobulinemic syndrome (CS) may be associated with other diseases; when it is not, it is t... more The cryoglobulinemic syndrome (CS) may be associated with other diseases; when it is not, it is termed essential. Recently the natural history of this disease has been re-evaluated on the basis of its close association with HCV markers. In this context, the GISC has studied a large series of patients from several Italian centres. In a multicentric retrospective study of 913 cases, we evaluated the clinical and laboratory signs at onset in patients with essential mixed cryoglobulinemias (EMC) (654 cases) or secondary cryoglobulinemias (SC) (259 cases) and sought to define possible diagnostic criteria typical of the different CS. We also carried out a retrospective 5-year cohort study on 192 patients selected randomly from the 913 cases described above. In particular, we examined the correlation between the presence/absence of concomitant diseases and the presence of HCV markers on the clinical evolution and survival of the patients. Purpura, rheumatoid factors (RF), significant C4 co...
La Ricerca in clinica e in laboratorio
Ninety-three patients with essential mixed cryoglobulinemia have been followed for more than 5 ye... more Ninety-three patients with essential mixed cryoglobulinemia have been followed for more than 5 years in 75% of cases; 21 patients died during this period and the mean age at death was 54 years. The most common cause of death was renal failure. The percentages of patients who survived after 5 and 10 years from the diagnosis were 87 and 74%, respectively. The cryoglobulin type seems to be an important prognostic factor: in our population the type II/III ratio is 6/7 at diagnosis, while it becomes 2/1 when the patients who died are considered.
La Ricerca in clinica e in laboratorio
A panel of autoantibodies has been tested in serum samples and cryoprecipitates of 14 patients af... more A panel of autoantibodies has been tested in serum samples and cryoprecipitates of 14 patients affected by essential mixed cryoglobulinemia (EMC) as well as in 12 subjects with secondary non-lupoid cryoglobulinemia (SC). Three out of 14 patients affected by EMC were ANA-positive (2 at 1:40 dilution and one at 1:80 dilution). Two out of 12 patients with SC were ANA-positive (both at 1:40 dilution). No autoantibodies were found in the cryoprecipitates. These data seem to confirm some previous observations and do not indicate a role of autoantibodies in the cryoprecipitate formation.
La Ricerca in clinica e in laboratorio
T lymphocyte subpopulations defined by monoclonal antibodies were determined in patients with ess... more T lymphocyte subpopulations defined by monoclonal antibodies were determined in patients with essential mixed cryoglobulinemia (EMC) and secondary cryoglobulinemias (SC). A decrease of circulating lymphocytes and a reduction in the absolute number of T3+, T4+ and T8+ (p less than 0.01) as well as in the percentage of T4+ lymphocytes (p less than 0.05) were found in EMC. A significant decrease of T8+ cells, both in percentage (p less than 0.01) and absolute number (p less than 0.001), was evidenced in SC, while T3+ and T4+ cell counts were not significantly different from those of healthy controls.
La Ricerca in clinica e in laboratorio
The clinical and immunochemical classification of 376 patients with cryoglobulinemia is presented... more The clinical and immunochemical classification of 376 patients with cryoglobulinemia is presented. In 141 cases (37.5%) the syndrome was considered idiopathic. Among the secondary forms, chronic liver diseases and connective tissue diseases shared most frequently mixed cryoglobulins (18.8 and 15.4% of cases, respectively). Another common association was that with Waldenström's macroglobulinemia: cryoglobulins were found in 20% of these patients. In 5 patients (2 with the essential form and 3 with cryoglobulinemia secondary to Waldenström's disease) a Cl-inhibitor deficiency was discovered; the complement profile was characteristic of the acquired type and episodes of angioedema occurred. Studying the clinical course of 71 cases of essential mixed cryoglobulinemia followed-up for 4-20 years we concluded that the evolution of type II and type III cryoglobulinemias is different because that of type II seems to have a more severe course and may differentiate in a lymphoprolifera...