Rituximab prevents recurrence of thrombotic thrombocytopenic purpura: a case report

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of small vessels that is associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. The presence of anti-ADAMTS13 autoantibodies is considered a factor predisposing to relapses. Despite close monitoring and intensive plasma treatment, in these patients acute episodes are still associated with substantial morbidity and mortality rates, and the optimal therapeutic option should be prevention of relapses. This study was conducted in a patient with recurrent TTP due to high titers of ADAMTS13 inhibitors, who used to have 2 relapses of TTP a year. The study compared the standard treatment plasma exchange with rituximab. Results documented that plasma exchange had only a small transient effect on ADAMTS13 activity and inhibitors; on the contrary, prophylaxis with rituximab was associated with disappearance of anti-ADAMTS13 antibodies, a progressive recovery of protease activity, and it allowed the patient to maintain a disease-free state during a more than 2-year follow-up.     

Prophylactic abciximab in elective coronary stenting: results of a randomized trial

BACKGROUND: The use of abciximab (c7E3 Fab; ReoPro , Eli Lilly & Company, Indianapolis, Indiana) during percutaneous coronary intervention (PCI) decreases the incidence of early (30-day) and late (6-month to 1 year) adverse cardiac ischemic events. In a high-risk population, abciximab also reduced the need for target lesion revascularization. PCI of lesions with complex morphology, particularly long lesions, is associated with more complicated outcomes. The use of multiple and/or long intracoronary stents to cover long coronary lesions may lower the incidence of acute or subacute occlusion, but is still limited by a high late restenosis rate. We characterized patients undergoing elective implantation of long or multiple overlapping coronary stents and determined the impact of abciximab administration on clinical and angiographic outcomes. METHODS AND RESULTS: In a prospective, single-center randomized trial, a total of 107 patients undergoing elective implantation of long or multiple overlapping coronary stents were randomly assigned to receive either standard-dose heparin (n = 53) or abciximab plus low-dose heparin (n = 54). The use of abciximab was not associated with an increased incidence of bleeding or vascular complications compared to standard heparin regimen (3.7% versus 3.8%, respectively; p = NS). A 68% reduction in composite in-hospital cardiac events (i.e., death, myocardial infarction, urgent revascularization) was observed in the abciximab group (3.7% versus 11.5%, p = 0.1). At 6-month follow-up, a 48% reduction of target lesion revascularization (11% versus 21%; p = 0.1) and a decrease in binary angiographic restenosis were observed for abciximab-treated patients (17% versus 34%; p < 0.05). CONCLUSION: The peri-procedural use of abciximab during implantation of long or multiple overlapping coronary stents is safe and effective, as it does not increase bleeding or vascular complications compared to standard heparin anticoagulation and reduces the incidence of in-hospital adverse cardiac events; moreover, abciximab improves 6-month clinical and angiographic outcomes in such a complex setting.     

The importance of being "not transplantable": an interesting patient

MitraClip therapy for Mitral Regurgitation(MR) in advanced-endstage heart failure(HF),could open a final bridge to improve symptoms and quality of life in \"not transplantable\" patients. We describe a homeless patient with NYHA class III HF, not elegible to heart transplantation for poor socio-economic status,and severe functional MR,treated with MitraClip. The patient was not suitable for conventional mitral valve repair because of high surgical risk and advanced HF (The STS mortality morbidity score=76%; EUROSCORE II=9,7%). Severe MR was confirmed at TEE preoperative evaluation of patient in which severe LV systolic dysfunction, diastolic dysfunction, severe right ventricle dysfunction, moderate tricuspid regurgitation and post-capillary pulmonary hypertension were detected. After 2 MitraClips implantation, TEE documented effective device position in relation to the main regurgitant jet, a MR grade reduction to 2 , with uneventful recovery. A gradual hemodynamic and general improvement was observed at three-month follow-up echocardiography documenting PAPs reduction and LVEF improvement. Beside, the patient showed HF symptoms reduction in NYHA class I-II. Management of functional MR in end-stage HF is an hard challenge, in addiction to the limited patient group feasibility and long-waiting list of heart transplantation. In the setting of this difficult current real-world experience, percutaneous tecnique was able to improve general conditions, quality of life and survival of our referred patient.     

Felodipine (once daily) versus nifedipine (four times daily) for Prinzmetal''s angina pectoris

In 30 consecutive patients with Prinzmetal's angina pectoris, the antiischemic effect of felodipine, a new long-acting vasoselective calcium antagonist, administered at doses of 10 and 20 mg once daily was compared with that of the wellestablished therapeutic regimen with nifedipine administered at a dose of 20 mg 4 times daily. Twenty-four-hour Holter monitoring was performed during a 2-day placebo run-in and at the end of each of 3 consecutive 6-day periods during which the 3 active treatments were administered in randomized sequence. Three patients withdrew, whereas 27 completed the study. The therapeutic regimens tested proved to be similarly effective; primary end points (ischemic episodes recorded by Holter monitoring, and anginal attacks reported on diary cards) occurred in 5 patients (19%) during nifedipine treatment, and in 7 (26%) and 3 (11%) during felodipine treatment with 10 and 20 mg, respectively (p = not significant). The distribution of residual ischemic episodes demonstrated that treatment with felodipine once daily provides 24-hour antiischemic protection. Twenty-six patients were followed up with 20 mg of felodipine once daily for a mean of 6 ± 5 months, and 21 of them (81%) remained free of symptoms and Holter-recorded ischemic attacks. It is concluded that for Prinzmetal's angina pectoris, 24-hour antiischemic protection may be achieved with administration of felodipine once daily. The availability of a simplified therapeutic approach may constitute a real advantage in terms of patient compliance and improving the quality of life.     

Frequency of the HFE gene mutations in five Italian populations

Genetic hemochromatosis is an autosomal recessive disorder characterized by iron overload and a variety of clinical manifestations such as liver cirrhosis and arthropathy. It is the most common genetic disease of northern European populations. The principal gene responsible for hereditary hemochromatosis, designated HFE, is located on chromosome 6 in the HLA region. The single point mutation 845A, changing cysteine at position 282 to tyrosine (C282Y), in this gene has been identified as the main genetic basis of hereditary hemochromatosis. Two other mutations, 187G, a histidine to aspartate at amino acid 63 (H63D), and 193T, a serine to cysteine at amino acid 65 (S65C), appear to be associated with milder forms of hereditary hemochromatosis. There is a high prevalence of the C282Y mutation in northern European populations, whereas in those of the Mediterranean basin the prevalence seems low and almost absent in Far East countries. This mutation seems usually to occur on the ancestral haplotype 7.1. Accordingly, a Celtic origin of this mutation has been suggested. The aim of this study was to determine the frequency of HFE gene mutations in five geographic regions in Italy. Samples were tested for C282Y, H63D, and S65C mutations of the HFE gene according to methods of each laboratory and the results were standardized with the exchange of typed samples between the different laboratories. In addition, C282Y-positive DNA samples were typed for D6S105 allele 8 and HLA-A3 by ARMS-PCR. We have found that the allele frequency of the C282Y mutation decreases from northeast Italy (Friuli, 6%) to northwest Italy (Piedmont, 4.8%) and to central Italy (Emilia-Romagna, 1.7%). However, this mutation is lacking in the two regions of the Mediterranean basin's center (Sicily and Sardinia). Accordingly, a significant difference in the frequency of the mutation was observed between these Italian regions (P = 0.07 x 10(-3)). In contrast, no difference was observed in allele frequency of H63D in the five Italian regions. Finally, as regards the S65C mutation a very low frequency was observed in Friuli, Emilia-Romagna, and Sardinia, whereas in Sicily and Piedmont we have not found this mutation. In conclusion, these data are consistent with the hypothesis that the C282Y mutation occurred in Caucasian populations of Celtic origin, whereas the H63D mutation is more ancient as demonstrated by the ubiquitous distribution.     

Continuous subcutaneous insulin infusion: A long-term study

Summary The authors report data obtained from a 3-year study of CSII and humanized insulin (semi-synthetic human insulin) administered to 18 insulin-dependent subjects in the outpatient clinic. The aim of this study was to evaluate the validity of insulin pumps in long-term treatment. Metabolic parameters were significantly improved (p<0.001) in the first month and remained so with only slight alterations throughout treatment. The authors underline some metabolic problems (ketosis) caused by malfunctioning of the insulin pumps, by the difficulties with the infusion sytem or by nodular skin lesions at the infusion site. Only these lesions called for treatment to be discontinued in 4 patients. The highest incidence of nodular skin lesions was seen after one year’s uninterrupted treatment and they seem connected to the duration of treatment rather than to the patients’ negligence (inadequate hygiene, delayed needle substitution). The authors conclude that CSII treatment is valid over short-term periods, whereas it presents drawbacks over long-term administration.     

Short-term treatment of gastric ulcer

Gastric ulcer is relatively infrequent, and clinical trials are often based on small-sized samples. The aim of this study was to define the gold standard therapy of active gastric ulcer. We included all single- or double-blind clinical trials on the short-term treatment of gastric ulcer. All the articles published over the period 1977–1994 were reviewed. Meta-analysis was done with both fixed and random effect models; results were shown using Galbraith's radial plot. Forty-eight papers comprising 52 studies were evaluated. Cimetidine, ranitidine, and famotidine proved significantly better than placebo [odds ratio (OR) and 95% confidence interval (CI 95%) at four to six weeks were: 2.67 (2.03–3.52), 3.94 (2.28–6.80), 1.76 (1.08–2.88), respectively]. Cimetidine and ranitidine had results comparable with the newer H₂ blockers [OR (CI 95%) at four weeks: 1.16 (0.91–1.47), 1.11 (0.80–1.55), respectively]. H₂ blockers were proved comparable with either sucralfate [OR (CI 95%) at eight weeks: 0.81 (0.37–1.79)] or bismuth [OR (CI 95%) at four to six weeks: 0.67 (0.37–1.20)]. Omeprazole is more effective than H₂ blockers [OR (CI 95%) at four weeks: 2.00 (1.57–2.55)]. It is concluded that H₂ blockers are preferred to either a placebo or sucralfate for short-term gastric ulcer treatment; the newer H₂ blockers do not have significant advantages over the older types; omeprazole can be regarded as the gold standard for active gastric ulcer treatment.The statistical analysis and computing with plot program was performed by G. Leandro, MD, Biostatistician. This work was performed under the auspices of the Roberto Farini Foundation for Gastroenterological Research.