Soluble CD30 serum levels before and after treatment with alpha-interferon in patients with chronic hepatitis C.

It has been suggested that soluble CD30 (sCD30) serum levels in chronic hepatitis C are correlated with the activity of the disease and with the outcome of interferon (IFN) treatment. In this study, sCD30 serum levels in 25 patients with chronic hepatitis C, before and after treatment with IFN-2alpha, were measured. A total of 20 healthy subjects were used as controls. High sCD30 levels in serum were found in 36% of patients and in 5% of controls. In patients with sCD30 levels above or within the normal range, no significant differences in age, gender, serum transaminases and histology activity index were found. In relation to IFN treatment, only responder patients had serum sCD30 higher than controls, although the difference between responders and non-responders was not significant. No changes from baseline values were observed after treatment. Although high, sCD30 serum levels in chronic hepatitis C are not correlated with the disease activity, are not affected by IFN treatment and are not predictors of response to IFN treatment.     

Regulatory mutations in transforming growth factor-beta3 gene cause arrhythmogenic right ventricular cardiomyopathy type 1

OBJECTIVE: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetically heterogeneous disorder characterized by fibro-fatty replacement of the right ventricular myocardium, associated with high risk of sudden death. The objective of this study is to identify the gene involved in ARVD1, which has been elusive ever since its locus was mapped to chromosome 14q24.3. METHODS AND RESULTS: Mutation screening of the promoter and untranslated regions (UTRs) of the transforming growth factor-beta3 (TGFbeta3) gene was performed by direct sequencing of genomic DNA of one index case belonging to an ARVD1 family including 38 members in four generations. We detected a nucleotide substitution (c.-36G>A) in 5' UTR of TGFbeta3 gene, invariably associated with the typical ARVC clinical phenotype in the affected family members, according to the established diagnostic criteria. Investigation extended to 30 unrelated ARVC patients, performed by denaturing high-performance liquid chromatography (DHPLC), led to the identification of an additional mutation (c.1723C>T) in the 3' UTR of one proband. Neither nucleotide change was found in 300 control subjects. In vitro expression assays with constructs containing the mutations showed that mutated UTRs were twofold more active than wild-types. CONCLUSION: We identified TGFbeta3 as the disease gene involved in ARVD1. The identification of a novel ARVC gene will increase the power of the genetic screening for early diagnosis of asymptomatic carriers among relatives of ARVC patients.     

Butyrophilin 3A (BTN3A,CD277)‐specific antibody 20.1 differentially activates Vγ9Vδ2 TCR clonotypes and interferes with phosphoantigen activation

Phosphoantigens (PAgs)‐like HMBPP ((E)‐4‐hydroxy‐3‐methyl‐but‐2‐enyl diphosphate) and butyrophilin 3 (BTN3A, CD277)‐specific monoclonal antibody 20.1 induce TCR‐mediated activation of Vγ9Vδ2 T cells. Here, we compared murine reporter cells transduced with Vγ9Vδ2 TCRs G115, D1C55, and MOP for the activation in culture with human RAJI cells and PAgs or mAb 20.1 and its single‐chain (sc) derivative. All transductants responded readily to PAg but only TCR MOP γ‐chain‐expressing cells responded to mAb/sc 20.1. Furthermore, both antagonist and agonist mAb and sc of the agonist mAb inhibited the PAg response of TCR‐transduced murine reporter cells. These findings suggest that, in contrast to stimulation by physiological stimulators (PAg), the responsiveness to mAb 20.1 depends strongly on CDR3 sequences of the TCR, and that mAb 20.1 can interfere with the PAg‐response. Mouse or human origin of reporter cells might affect the mAb 20.1 response since all three TCR‐mediated mAb 20.1‐induced activation of TCR‐transduced Jurkat cells. The pronounced differences between PAg and mAb 20.1‐induced activation observed here help to understand the often contradictory published data. This study provides novel perspectives on the physiological mechanism of Vγ9Vδ2 T‐cell activation, and highlights the complex mode of action of BTN3A‐specific antibodies as agents in cancer immunotherapy.     

Long-term follow-up of right ventricular monomorphic extrasystoles

OBJECTIVES: The purpose of this study was to verify in a long-term follow-up whether frequent monomorphic right ventricle extrasystoles may progress to arrhythmogenic right ventricular dysplasia (ARVD). BACKGROUND: Frequent monomorphic right ventricle extrasystoles are generally considered benign. However, in patients with this pattern, cardiac magnetic resonance (MR) has recently shown anatomical and functional abnormalities of the right ventricle. METHODS: Sixty-one patients who had been classified by noninvasive examinations as having frequent idiopathic right ventricle ectopy were contacted after 15 +/- 2 years (12 to 20) and submitted to clinical examination, electrocardiogram (ECG), Holter monitoring, stress test, signal averaged ECG, echocardiography and, in 11 patients, cardiac MR. The primary end point was to ascertain the presence of cases of sudden death or progression to ARVD. RESULTS: At the end of the follow-up, 55 patients were alive; six died, none of sudden death; eight stated to be well but refused further examinations. The 47 patients examined had normal ECG; in 24 patients (51%), extrasystoles were no longer present at Holter monitoring; late potentials were present in up to 15% of the patients; the right ventricle was normal at echocardiography. In 8 of 11 patients (73%), cardiac MR showed focal fatty replacement and other abnormalities of the right ventricle. CONCLUSIONS: In this long-term follow-up study, no patient died of sudden death nor developed ARVD; two-thirds of the patients were asymptomatic, and, in half of the patients, ectopy had disappeared. Focal fatty replacement in the right ventricle was present in most.     

Outbreak of W135 meningococcal disease in 2000: not emergence of a new W135 strain but clonal expansion within the electophoretic type-37 complex

In 2000, >400 cases of disease caused by Neisseria meningitidis serogroup W135 (MenW135), the largest MenW135 outbreak reported to date, occurred worldwide among Hajj pilgrims and their contacts. To elucidate the origin of the outbreak strains and to investigate their relatedness to major clonal groups, genotypic and phenotypic subtyping was performed on 26 MenW135 outbreak-associated isolates and 50 MenW135 isolates collected worldwide from 1970 through 2000. All outbreak-associated isolates were members of a single clone of the hypervirulent electrophoretic type (ET)-37 complex, designated the "(W)ET-37 clone"; 19 additional MenW135 strains were also members of this clone, and the remaining 31 MenW135 strains were clearly distinct. The 2000 MenW135 outbreak was not caused by emergence of a new MenW135 strain but rather by expansion of the (W)ET-37 clone that has been in circulation at least since 1970; the strains most closely related to those causing the 2000 outbreak have been isolated in Algeria, Mali, and The Gambia in the 1990s.     

The gold standard in the treatment of haemorrhoidal disease. Milligan-Morgan haemorrhoidectomy vs Longo mucoprolapsectomy: comparing techniques

AIM: Although mucosectomy according to Longo was a real revolution in the treatment of haemorrhoidal disease, Milligan-Morgan haemorrhoidectomy, maintaining the characteristics of a technique which is physiopathologically efficacious and easily performed, is still the procedure of choice in some clinical conditions. The aim of this study was to evaluate which of the two techniques, Milligan-Morgan haemorrhoidectomy and Longo mucoprolapsectomy, could be considered the gold standard in the treatment of haemorrhoidal disease. METHODS: From March 2002 to October 2006, in the VII Department of General Surgery of SUN, we compared two groups of 26 patients each: one treated with Milligan-Morgan haemorrhoidectomy, the other one with Longo mucoprolapsectomy. Among the patients treated with traditional technique, 16 were suffering from grade III haemorrhoids and prolapse, while the other 10 from grade IV haemorrhoids and prolapse. The group treated with stapler was composed of 10 patients affected by grade III haemorrhoids and prolapse, while the other 16 were patients complaining for grade IV haemorrhoids and prolapse. For both groups of patients the follow-up lasted 12 months; they were controlled at 1 week, 1 month, 6 months and 1 year after the operation. RESULTS: The level of pain measured with a visual analogue scale (VAS) was always higher in the group treated with traditional technique. In 69% of the patients treated with stapler and in 59% of those treated with open technique there was the first defecation within postoperative day 2. The return to normal activity was earlier in patients who underwent Longo technique. Among the patients treated with traditional technique, 7.7% had postoperative bleeding, 15.4% at the 6-month control, suffered from anal fissure with associated high pressure of anal sphincter and tenesmus and 7.7% showed a recurrence after 1 year. In the group treated with Longo technique, 11.54% of the patients had a postoperative haemorrhage at the 6-month control, 7.7% showed substenosis, 3.84% of the patients felt tenesmus; in 3.84% of the cases a perianal extra-sphincteric fistula was evident. At 1 year control, 11.54% of the patients showed recurrences. CONCLUSION: The conclusion is drawn that it does not exist any indication for the Longo technique; however, it seems to give the best results in grade III haemorrhoids with prolapse, without sphincteric implications.