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Aim: The aim of this study was to evaluate short- and long-term results of PCI (percutaneous coronary intervention) in patients with small vessel coronary artery disease and the prognostic impact of the extension and the length of coronary lesions., Methods and Results: All consecutive patients treated with PCI in our centre between July 2002 and December 2004 were included and divided into two groups according to the diameter of the implanted stents: small vessel disease was defined as requiring implantation of stents < 2.75 mm in diameter. The primary end point was the long-term incidence of major adverse cardiac events (MACE), the composite of cardiac mortality, nonfatal myocardial reinfarction, and repeated percutaneous target vessel revascularization (re-PTCA TVR). 1599 patients were treated by PCI: 419 (26.2%) were implanted with 2.75 mm or smaller stents. At both 1 and 36 months as well as at 53 + 20 months of follow-up small vessel stenting was associated with a higher rate of MACE (4.2% vs 2.1%, P= 0.028; 20.3% vs 17.9%, P <0.001; 27.5% vs 22.4%, P= 0.04, respectively). Multivariate analysis showed higher rates of revascularization for patients with small vessel disease regardless of lesion length. Rates of death were higher in patients with small vessels and long lesions., Conclusion: Atherosclerotic involvement of small vessels in patients with CAD confers a higher short- and long-term risk of adverse outcome after PCI.

Introduction: Coronary artery disease (CAD), along with its main complications such as acute myocardial infarction (AMI) and congestive heart failure (CHF), remains a serious worldwide problem and affects many patients despite the improvement of medical treatment. The possibility of the replacement of the infarcted areas by the re-generation of the myocardial cells has been long discussed and the mobilization of the stem cells from bone marrow (BMCs) to the peripheral blood (PB) induced by cytokines, represents a potential pathway to activate the regenerative process., Patients and Methods: We describe BMC mobilization and direct/indirect revascularization in 15 patients operated on for coronary artery bypass grafting (CABG) and/or mitral valve surgery and/or ventricular remodeling combined to multiple trans-myocardial punctures (Sen technique) in ungraftable non-viable fibrotic areas., Results: Peak values of circulating BMCs were recorded between day +4 and day +6. We had no in-hospital (0-30 days) mortality. All the patients were discharged from the ICU after a median period of 2 days while the in-hospital length of stay was 10.5+4.2 days (range 7-21) and all patients were discharged in good clinical condition. There were two sudden deaths over the mid-term, at postoperative day (POD) 32 and 45 respectively., Conclusions: Our study suggests that the combination of BMC mobilization and CABG may be safely performed. However, considering the small series, final conclusions about the benefit of this procedure must await a larger prospective study comparing the role of cytokines alone, myocardial perforation, and the combination of both.

Objectives: We aimed to appraise the early and long-term outcome after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) in patients with unprotected left main disease (ULM) and left ventricular systolic dysfunction (LVD)., Background: PCI with DES has being performed with increasing frequency in subjects with ULM and LVD, but few specific data are available., Setting and Patients: We identified patients undergoing PCI with DES for ULM at our Center and distinguished those with ejection fraction (EF) >50% from those with 40% 50%, 32.0% with 40% 50%, 41.6% in those with 40%

Aim: Diabetics with coronary artery disease face a high risk of adverse events following coronary revascularization. However, recurrence rates of after the first revascularization have never been appraised. The aim of this study was to evaluate recurrent events in diabetics undergoing percutaneous coronary intervention (PCI) in the current era., Methods: Authors collected baseline and outcome data of consecutive type-2 diabetics treated with PCI (July 2002-December 2005) . End-points of interest were the long-term rates of major adverse cardiac events (MACE: cardiac death, myocardial infarction [MI], percutaneous target vessel revascularization [TVR-PCI], or coronary artery bypass grafting [CABG]), non-TVR PCI, and stent thrombosis., Results: A total of 429 diabetics were included, 191 (44%) insulin-dependent, with drug-eluting stents implanted in 232 (54%). After a median of 38 months, events were as follows: MACE in 167 (38.9%) subjects, cardiac death in 38 (8.8%), MI in 42 (9.8%), TVR-PCI in 130 (30.3%), CABG in 11 (2.6%), non-TVR-PCI in 52 (12.1%), and definite stent thrombosis in 9 (2.1%). Among the 129 patients undergoing TVR-PCI as first event, as many as 28 (21.7%) underwent a second TVR-PCI, 7 (5.4%) underwent a third TVR-PCI, and a further 2 (1.5%) underwent a fourth TVR-PCI, whereas CABG was performed in 2 (1.5%) and non-TVR-PCI in 4 (3.1%)., Conclusions: This work, originally reporting on the risk of recurrent repeat revascularization events among diabetics treated with PCI, showed that adverse events occur frequently in these patients, but can be managed in most cases safely and successfully by means of repeat PCI only.

Background and Aims: The aim of this study was to evaluate and characterize the feasibility and safety of bone marrow-derived cell (BMC) mobilization following repeated courses of granulocyte-colony stimulating factor (G-CSF) in patients with amyotrophic lateral sclerosis (ALS)., Methods: Between January 2006 and March 2007, 26 ALS patients entered a multicenter trial that included four courses of BMC mobilization at 3-month intervals. In each course, G-CSF (5 microg/kg b.i.d.) was administered for four consecutive days; 18% mannitol was also given. Mobilization was monitored by flow cytometry analysis of circulating CD34(+) cells and by in vitro colony assay for clonogenic progenitors. Co-expression by CD34(+) cells of CD133, CD90, CD184, CD117 and CD31 was also assessed., Results: Twenty patients completed the four-course schedule. One patient died and one refused to continue the program before starting the mobilization courses; four discontinued the study protocol because of disease progression. Overall, 89 G-CSF courses were delivered. There were two severe adverse events: one prolactinoma and one deep vein thrombosis. There were no discontinuations as a result of toxic complications. Circulating CD34(+) cells were monitored during 85 G-CSF courses and were always markedly increased; the range of median peak values was 41-57/microL, with no significant differences among the four G-CSF courses. Circulating clonogenic progenitor levels paralleled CD34(+) cell levels. Most mobilized CD34(+) cells co-expressed stem cell markers, with a significant increase in CD133 co-expression., Conclusions: It is feasible to deliver repeated courses of G-CSF to mobilize a substantial number of CD34(+) cells in patients with ALS; mobilized BMC include immature cells with potential clinical usefulness.

Coronary bifurcation lesions represent an area of ongoing challenge in interventional cardiology. Contemporary studies using drug-eluting stents report a reduction in main vessel (MV) restenosis; however, residual stenosis and restenosis at side-branch ostium remain an issue. Multiple two-stent bifurcation strategies exist, including T-stenting, V-stenting, simultaneous kissing stenting, culotte stenting, and crush stenting technique. Each strategy has its own advantages and disadvantages, but on the basis of results of numerous randomized trials, the provisional approach of implanting one stent on the main branch has became the default approach to most bifurcation lesions. Dedicated bifurcation stents have been designed to specifically address some of the shortcomings of the conventional percutaneous approach to bifurcation intervention. The majority of the devices are aimed at facilitating the provisional approach. Dedicated bifurcation stents should enable all operators to treat the side-branch ostium simultaneously with the main branch, preserving a safe, permanent access to side branch during the procedure. In the future, the use of these new devices will probably enhance the interaction between adequate mechanical scaffolding and accurate delivery of the appropriate dosage of any new antirestenosis drugs. There are currently 11 devices available that either have completed or are undergoing first-in-man trials. The development of further drug-eluting platforms and larger controlled studies should demonstrate their clinical applicability, efficacy, and safety before they are widely incorporated into daily practice.

Objectives: We aimed to conduct a retrospective cohort study focusing on our 5-year experience in the percutaneous treatment of unprotected left main (ULM) trifurcation disease., Background: Percutaneous treatment of ULM trifurcation remains a challenging and rare procedure for most interventional cardiologists. Moreover, data on long-term outcomes are lacking., Methods: We retrieved all patients with ULM trifurcation disease treated percutaneously at our Institution since 2002, and adjudicated baseline, procedural, and outcome data. The primary end point was the long-term rate of major adverse cardiovascular events (MACE, i.e., cardiac death, myocardial infarction, bypass surgery, or target vessel revascularization)., Results: A total of 27 patients underwent percutaneous coronary intervention with stent implantation for ULM trifurcation disease, with 14 (52%) cases of true trifurcations, i.e., with concomitant significant stenoses of the distal ULM/ostial left anterior descending plus ostial ramus intermedius and ostial circumflex. Bare-metal stents were implanted in 8 (29%) patients and drug-eluting stents (DES) in 26 (96%), with a main branch stent only strategy in 11 (40%), T stenting in 9 (33%), and V stenting in 6 (27%). Procedural and clinical success occurred in 26 (96%), with one postprocedural death. Angiographic follow-up was obtained in 22 patients (81%), and clinical follow-up was completed in all subjects after a median of 28 +/- 17 months, showing overall MACE in 9 (33%), with cardiac death in 4 (15%), myocardial infarction in 1 (4%), coronary artery bypass grafting (CABG) in 4 (15%), and percutaneous target vessel revascularization in 5 (19%). Definite stent thrombosis was adjudicated in 1 (3%) patient. Treatment of a true trifurcation lesion and recurrence of angina during follow-up were significantly associated with an increased risk of MACE (P = 0.029 and P = 0.050, respectively)., Conclusions: Percutaneous treatment of ULM trifurcation disease is feasible, associated with favorable mid-term results, and may be considered given its low invasiveness in patients at high surgical risk or with multiple comorbidities., ((c) 2008 Wiley-Liss, Inc.)

Background: Coronary chronic total occlusions (CTO) remain a challenging lesion subset for interventional cardiologists. The retrograde approach is a novel but still incompletely described technique. We report our 5-year-long experience in retrograde percutaneous coronary intervention (PCI) for CTOs., Methods: We abstracted patient and procedural data on all cases with attempted retrograde approach by means of a native septal or epicardial collateral pathway. End-points were wiring, angiographic and procedural success, plus long-term major adverse cardiovascular events (MACE)., Results: The retrograde approach was used in 18 patients, including 11 CTOs of right coronary artery (RCA), 3 of left circumflex (LCX), and 4 of left anterior descending (LAD), with procedural success in 12 (67%). Conversely, two cases of wiring failures, three angiographic failures despite successful retrograde wiring, and one postprocedural myocardial infarction in an otherwise angiographically successful procedure were found. Causes of wiring failure were inability to retrogradely cross the distal (1) or the proximal stump (1) with the wire, while angiographic failures were due to interruption of the procedure due to rupture of a minor septal collateral branch during attempts at advancing the noninflated balloon (1) or persistent inability to deliver the balloon through the chosen collateral (2). Follow-up at a mean of 15 months showed MACE had occurred in five (28%) subjects., Conclusions: The retrograde approach appears feasible and safe in the percutaneous management of coronary occlusions, and its application can be envisioned as a promising alternative in selected patients in whom antegrade approaches fail or are unsafe.

Monoclonal antibodies (MoAbs) specific for the antigens associated with each stage of an inflammatory response were assayed with tonsillar mononuclear cells (TMNG). MoAbs BMA 27 E 10 and BMA 4 D 10 were used as markers for the early stages, BMA RM 3/1 for the intermediate stage, BMA 25 F 9 for the late stage, and BMA G 16/1 for the chronic stage. TMNC were obtained from patients operated for (1) recurrent tonsillitis with hypertrophy caused by common flora (children); (2) an indication for surgery for chronic tonsillitis in adults; (3) patients who were 'warm' tonsillectomized for a second peri-tonsillar phlegmon. Our results are presented and discussed in the light of their possible clinical significance. Our findings indicate that clinical chronic tonsillitis in the adult really is such. In the adults studied there was a high expression of antigens which is associated with the chronic stages, while the low expression of antigens is associated with the intermediate stage and an even lower antigen expression indicates the acute stage. In children what is considered to be chronic tonsillitis may perhaps be more correctly regarded as an expression of recurrent inflammation.

Haemopoietic growth factor administration following high-dose chemotherapy markedly amplifies progenitor cell pool in the peripheral blood (PB). Collection and reinfusion of these cells enable rapid haemopoietic reconstitution following autograft. Less is known on engraftment potentiality of bone marrow (BM) cells taken under analogous conditions. To investigate this tissue, PB and BM were evaluated simultaneously during maximal mobilization in a series of 14 patients undergoing the HDS chemotherapy programme. A significantly higher growth of committed progenitors was found from PB rather than from BM (663 +/- 123 v 267 +/- 40 CFU-GM/10(5) MNC, respectively). Also, significantly more CFU-GM could be collected by a median of three leukaphereses, compared to those harvested from BM (158 +/- 31 v 16 +/- 4 x 10(4) CFU-GM/kg, respectively). Most mobilized CFU-GM were phenotypically immature (CD15-); in addition, circulating cells included primitive progenitors, as assessed by LTC-IC assay, or by evaluation of non-proliferating pre-CFU-GM, selected by an anti-CD71 immunotoxin. The amount of pre-CFU-GM determined by both techniques was consistently higher in PB than in BM. Moreover, a direct correlation could be established between circulating CFU-GM and primitive precursors. Thus, during optimally induced mobilization, PB contains many more haemopoietic progenitors, of both committed and primitive stages, than does BM. Under such conditions, PB is probably the best source of material for graft purposes.

Multiple myeloma (MM) is a B-cell malignancy characterized by clonal expansion of plasma cells producing monoclonal immunoglobulins. It has been regarded as a tumor typically involving only the bone marrow. The existence of circulating tumor cells has been suggested from phenotypic and genotypic studies. However, this issue is still controversial due to the limitations of the methods so far used. We describe a novel polymerase chain reaction (PCR) based method using clone-specific immunoglobulin heavy-chain gene sequences as tumor markers. From such sequences patient-specific oligonucleotide primers and probes were generated, and used to detect tumor cells. Seven MM patients were selected for this study, and tumor cells were found in all peripheral blood samples. The demonstration of circulating tumor cells suggests some caution when using peripheral blood for autograft procedures, even though its contamination is lower than bone marrow. In conclusion, we describe a specific and sensitive PCR-based method for detecting minimal disease which is of general applicability to all lymphoid malignancies transcribing rearranged immunoglobulin heavy-chain genes.

We have recently shown that peripheral blood T cells of multiple myeloma (MM) patients are very susceptible to stimulation of the T-cell receptor/CD3 complex with anti-CD3 monoclonal antibodies (MoAbs). CD3 stimulation is currently under clinical investigation as a nonspecific approach to boost antitumor effector mechanisms. The aim of this study was to determine whether the hyperreactivity of MM T cells to CD3 stimulation could be exploited to generate antitumor activity. Bone marrow mononuclear cells (BMMCs) from 65 MM patients were stimulated with the anti-CD3 MoAb OKT3 and the effect of this stimulation on autologous T cells and plasma cells was evaluated. The number of CD3+ CD25+ cells on day 6 was significantly higher in MM than the controls (30 normal individuals) (P = .001). Kinetic studies showed that 3H-thymidine incorporation peaked on day 3 and that the T-cell expansion peaked on days 5 and 6. In MM, T-cell activation markedly affected the survival of autologous plasma cells; their number in OKT3-treated cultures was significantly lower than in unstimulated cultures (P < .0001). T-cell activation and plasma cell decrease were not observed when T cells were removed from BMMC preparations. MM produced significantly higher levels of interferon-gamma (P = .005) and tumor necrosis factor-beta (P = .001), but lower levels of tumor necrosis factor-alpha (P < .001) than normal individuals. Interferon-gamma only was partially involved in CD3-induced plasma cell killing. Transwell cultures showed that the main mechanism by which CD3+ CD25+ cells affected plasma cells was direct cell-to-cell contact rather than cytokines. In conclusion, T cells in MM BMMCs possess distinct features in terms of susceptibility to CD3 stimulation and cytokine production compared with normal bone marrow T cells that can be exploited to generate antiplasma cell activity.

Circulating hemopoietic progenitors were evaluated in 19 multiple myeloma patients at diagnosis. Eleven patients received either high-dose cyclophosphamide (7 g/m2, 8 patients) or etoposide (2 g/m2, 3 patients) followed by GM-CSF administration; the remaining 8 patients received intermediate-dose cyclophosphamide (1.2 g/m2 on days 1 and 3), 4 of them with GM-CSF support. The highest levels of circulating progenitor cells were observed among patients in the high-dose chemotherapy group (median CFU-GM peak value of 6432 per ml), while in patients receiving intermediate-dose, with or without GM-CSF, median peak values were 2588 and 462 per ml, respectively. In all groups a remarkable heterogeneity in the yield of circulating progenitors was observed; this was particularly pronounced in the high-dose group, where CFU-GM peak values ranged between 200 and 38,070 per ml. At variance with the effect observed in previously untreated patients with lymphoma or breast cancer, the degree of mobilization in myeloma patients was rather unpredictable. The only pre-treatment characteristic correlating to some extent with a poor expansion of the circulating progenitor pool was heavy BM infiltration with plasma cells. The mobilizing effect was not restricted to the myeloid lineage, as demonstrated by the rise of BFU-E; CD34+ cells were increased as well. Indeed, a simultaneous evaluation of CFU-GM and CD34+ cells was carried out and a highly significant correlation (r = 0.9) was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

IgG and IgA immune complexes, mononuclear phagocytic system function, interleukin-2 (IL-2) production by peripheral blood lymphocytes (PBL), serum-soluble IL-2 receptors, tumor necrosis factor, beta 2-microglobulin and IL-1 beta, HLA-DNA polymorphisms, immuno-isoelectrofocusing, phenotype of PBL, lymphocyte cytotoxicity, activation of lymphokine-activated killer cells and natural killer cell activity were evaluated in 8 patients with tubular/fibrillary glomerulonephritis (GN). No common serologic, immunologic or immunogenetic features suggestive of plasma cell dyscrasias were found. No elements to state whether these GNs represent a new entity or just atypical forms of known GN were found.

Background: IFN-alpha has recently been shown to prolong the remission phase in MM patients with low tumor mass. So far, it is not known whether IFN-alpha exerts its effect directly on the myeloma cells or is mediated by modulation of the host response., Methods: The immune status of 12 multiple myeloma patients with low tumor mass (10 in remission phase, 2 with stage IA disease) was investigated by phenotypic and functional analyses before, after 3, and after 6 months of recombinant interferon-alpha 2b (IFN-alpha) therapy., Results: Phenotyping of peripheral blood lymphocytes (PBL) revealed a significant decrease of HLA-DR+ (P = 0.01) and CD20+ (P = 0.04) cells after 6 months of therapy. Two-color phenotyping of purified T cell populations (PBT) showed a significant increase of CD4+ CD11b+ cells (P = 0.01) after 6 months of therapy. Functional analyses were carried out on PBL (NK cell-mediated cytotoxicity) and PBT (alloreactive cytotoxicity, CTL; IL2-induced cytotoxicity, LAK activity). NK and CTL activities were poorly influenced by IFN-alpha treatment, whereas LAK activity showed a significant increase (P = 0.007). Any significant association between these immunological changes and the disease status was questioned by the lack of differences between MM in relapse and MM with stable disease at the sixth month of IFN-alpha therapy., Conclusions: i) IFN-alpha in MM with low tumor mass may exert its therapeutic activity by directly acting on the tumor cells; ii) the parameters which have been used in this study are not appropriate to monitor the immunological effects (if any) of IFN-alpha therapy.

Twenty pediatric patients with recurrent infectious diseases of the upper respiratory tract (tonsillitis, adenotonsillitis with or without involvement of the ear and/or lower respiratory tract) were studied. An immunological assay of the nasal secretum was performed at time of diagnosis and following treatment with a local immunomodulator drug, administered by spray. The 7S, 11S IgA and albumin rates were evaluated. The authors emphasize the importance of SIgA in mucose defense mechanisms as well as the need for a selective method for determining the 11S IgA level. An original method for immuno-isoelectrofocusing (IIEF) determination was employed in the present study. After treatment a significant increase in 11S IgA level was observed, especially in those patients with a significant basal SIGA deficit. The authors describe details of the technique for determination and discuss the results.

In multiple myeloma (MM) an increase in circulating lymphocytes expressing plasma cell-associated antigens (PCAA) has been described. Its prognostic significance was evaluated in this study. The immunologic phenotype of peripheral blood lymphocytes was analyzed with a panel of monoclonal antibodies specific for B, T, natural killer lymphocytes, and PCAA (CD38, PCA1) in 52 MM patients at diagnosis, remission, and during relapse, 18 monoclonal gammopathy of undetermined significance (MGUS), and 25 normal controls. No significant phenotypic alteration was observed in MGUS. In MM, the number of B lymphocytes was in the normal range at diagnosis and during the subsequent phases. A CD4/CD8 ratio decrease, during relapse, was due to both a CD4+ reduction and to an expansion of a subset of CD8+ activated suppressor lymphocytes. CD38+ and PCA1+ lymphocytes at diagnosis were significantly higher than in MGUS, and a further increase was observed during relapse, suggesting a correlation between PCAA expression and disease activity. The prognostic significance of increased PCAA was confirmed by a survival analysis of 32 patients evaluated at diagnosis using a CD38 cutoff of 0.45 x 10(9)/L positive lymphocytes. Median survival for patients with high values was only 14 months, whereas it was not reached at 32 months by those with low values (P less than .0007).

Peripheral blood lymphocytes from 9 monoclonal gammopathies of undetermined significance (MGUS) and 27 multiple myelomas (MM) were studied with a panel of monoclonal antibodies (MoAb) that recognize B and T lymphocytes and plasma cells. No difference in the percentage of B lymphocytes, identified by B1 and B4 MoAb, was observed in MGUS and MM patients versus normal controls. However, high percentages of circulating lymphocytes expressing plasma cell-associated antigens were detected in MM (HAN-PC1+ = 29.4 +/- 20.4%; TEC-T10+ = 27.8 +/- 19.2%) whereas they were in the normal range in MGUS (HAN-PC1+ = 8.8 +/- 5.8% p = 0.006; TEC-T10+ = 5.7 +/- 4.7% p less than 0.001). Almost identical results were obtained using PCA-1 MoAb in 17 of these patients. TEC-T10+ and PCA-1+ lymphocytes were sorted and re-analyzed with phycoerythrin conjugated MoAb in 3 healthy subjects, 2 MGUS, and 4 MM patients. In normal subjects and in MGUS the majority of PCA-1+ cells belonged to the B lineage (Leu 2-, Leu3-, Leu 15-, HLA-Dr+), whereas the majority of TEC-T10+ cells are represented by activated T cells and NK cells (Leu 15+). In MM an abnormal expansion of T lymphocytes was chiefly responsible for the high values of lymphocytes expressing plasma cell-associated antigens. Moreover, in MM a clinical evaluation showed a correlation between the presence of these lymphocytes and an aggressive disease. Indeed, they can be considered a useful prognostic marker.