Antibodies to proteins from Pityrosporum ovale in the sera from patients with psoriasis

In order to analyse the humoral immune response to the commensal yeast Pityrosporum ovale, we developed a western immunoblot technique with a salt soluble extract of P. ovale cytoplasm. In the present study, we tested sera from patients with psoriasis (n= 15), seborrhoeic dermatitis (n= 10), pityriasis versicolor (n= 8), and normal controls (n = 10). Seventy-three per cent (11/15) of the patients with psoriasis showed specific reactivity with a protein derived from P. ovale of estimated molecular mass 120 kDa, and 46% (7/15) of the cases recognized a 100-kDa protein. Sera from pityriasis versicolor and normal donors showed nonspecific reactivity with several bands of lower molecular weight. To characterize the location of the 100 and 120-kDa proteins, we performed a lyticase digestion of the cell wall, and analysed the soluble digested products by western blotting. The sera from psoriasis patients detected several bands in the range 100–120 kDa. The finding of the immunoreactive 120-kDa protein in this fraction suggests its location at the space between cell wail and membrane (periplasmic space). As a control, we performed an extraction of the cytoplasmic proteins of the dimorphic yeast Candida albicans. C. albicans showed a different pattern of banding in SDS–PAGE. Immunoblots with C. albicans did not allow the detection of any related band. A smear was observed in the high molecular weight range consistent with the presence of lipopolysaccharides. The role of the immune response in infection by P. ovale has not yet been fully explored. The function of the antibodies recognizing 100-120-kDa bands in the majority of the patients with psoriasis seems to represent a specific immune response to the yeast phase of P. ovale.     

Allogeneic bone marrow transplantation versus chemotherapy in high-risk childhood acute lymphoblastic leukaemia in first remission

We compared the outcome of children with high-risk acute lymphoblastic leukaemia (HR-ALL) in first complete remission (first CR) treated with chemotherapy (CHEMO) or with allogeneic bone marrow transplantation (BMT) in a multicentre study.   All children treated by the Italian Paediatric Haematology Oncology Association for HR-ALL in first CR between 1986 and 1994 were eligible for the study. 30 children were given BMT at a median of 4 months from first CR, with preparative regimens including total-body irradiation ( n  =25/30). 130 matched controls for BMT patients were identified among 397 HR-ALL CHEMO patients. Matching on main prognostic factors and duration of first CR was adopted to control the selection and time-to-transplant biases. The comparative analysis was based on the results of a stratified Cox model. The estimated hazard ratios of BMT versus CHEMO at 6 months, 1 year and 2 years after CR were 1.38 (CI 0.59–3.24), 0.69 (CI 0.27–1.77) and 0.35 (CI 0.06–1{\raise 5mu ..91), with an overall non-significant difference between the two groups ( P  = 0.34). With a median follow-up of 4 years, the disease-free survival was 58.5% (SE 9.3) in the BMT group and 47.7% (SE 4.8) in the CHEMO group, at 4 years from CR. Non-leukaemic death occurred in 4% of CHEMO and 10% of BMT patients. In the BMT group the estimated cumulative incidence of relapse at 1.5 years from CR was 31.5% (SE 8.8) and did not change thereafter, whereas in the CHEMO group the corresponding figure was 29.2% (SE 4.1) and the incidence continued to increase thereafter (48.2% (SE 4.8) at 4 years from CR).   The results of this study suggest that, with respect to the CHEMO group, the higher risk of early failure in the BMT group is outweighed by the lower risk of relapse after 1 year. Results prompt the need for a prospective study, in order to demonstrate the likely advantage of BMT in HR childhood ALL in first CR.     

Cardiac arrhythmia and ischaemic events after combination chemotherapy for testicular cancer

The aim of the present investigation was to evaluate the typeand the incidence of cardiac arrhythmias and ischaemic eventsin patients suffering from testicular cancer and submitted tocombination chemotherapy with cisplatin, bleomycin and vinblastine(PVB) or etoposide (PEE). Forty-seven patients took part inthe study; 23 were treated with PVB and 24 with PEB. Holiermonitoring was performed in each patient before chemotherapyand on the 1st, 2nd and 5th day of the first cycle of drug administration.The results showed that combination chemotherapy with PVB orPEB was accompanied by the appearance of or an increase in,the incidence of supraventricular ectopic beats. No significantdifference was found between the two groups. No significantconduction disturbances were recorded. These results show that combination chemotherapy with PVB orPEB, at least during the first cycle, has no significant ventriculararrhythmogenic or ischaemic potency in young people with nohistory of cardiac disease.     

Flecainide Test in Brugada Syndrome: A Reproducible but Risky Tool

GASPARINI, M., et al .: Flecainide Test in Brugada Syndrome: A Reproducible but Risky Tool. The flecainide test is widely used in Brugada syndrome. However, its reproducibility and safety remain ill-defined. This study included 22 patients (18 men, mean age 34 years). Mutations in the SCN5A gene were found in eight patients. Two patients had aborted sudden cardiac death, 8 had syncope/presyncope, and 12 were asymptomatic. The ECG was diagnostic in 19 patients and suggestive in 3. At baseline, 21 of 22 patients underwent a flecainide test (2 mg/kg IV bolus over 10 minutes). In 21 of 21 patients the test was diagnostic or amplified the typical ECG pattern. At the end of drug infusion, sustained VT lasting 7–10 minutes developed in two patients. A second flecainide test was performed within 2 months in 20 patients. The test was not repeated in the two patients with prior development of VT. The flecainide test was diagnostic in 20 of 20 patients. Sustained VT occurred in one patient and recurrent VF in another. The reproducibility of the flecainide test was 100%. In 4 (18%) of 22 patients major VAs were documented after the end of flecainide infusion. VA occurred in 3 (43%) of 7 patients with, versus 1 (7%) 15 without SCN5A gene mutation (P < 0.05). No diagnostic ECG changes or arrhythmias developed in 25 control patients without structural heart disease who underwent the same study protocol. This study shows a high flecainide reproducibility, supporting its diagnostic value in Brugada syndrome. However, the occurrence of major VA, significantly higher in patients with documented SCN5A gene mutation, including in asymptomatic patients, mandates the performance under appropriate medical supervision. Whether a slower rate of drug infusion can lower the risk of VA induction, while maintaining the sensitivity of the test should be explored. (PACE 2003; 26[Pt. II]:338–341)     

Three Years of Cardiac Resynchronization Therapy: Could Superior Benefits be Obtained in Patients with Heart Failure and Narrow QRS?

Aim of the study: To examine the long-term effects of cardiac resynchronization therapy (CRT) in patients presenting with heart failure (HF) and QRS ≤120 ms.
Methods: This was a prospective, longitudinal study of 376 patients [mean age = 65 years, mean left ventricular (LV) ejection fraction (EF) = 29%, mean QRS duration =165 ms, mean distance covered during a 6-minute hall walk (6-MHW) = 325 m], who underwent successful implantation of CRT systems. The QRS duration at baseline was ≤120 ms in 45 patients (12%) who were not pre-selected by echocardiographic criteria of dyssynchrony, and >120 ms in the remaining 331 patients. The baseline characteristics of the 2 groups were similar. We evaluated indices of cardiac function, percentage of responders, and survival rates over a mean 28-month follow-up.
Results: Both groups experienced similar long-term increases in 6-MHW, and decreases in New York Heart Association functional class and LV end-systolic volume (all comparisons P < 0.0001 in both groups). Time interaction of changes in LVEF and percentage of responders were significantly different (P = 0.03 and P = 0.004, respectively), in favor of the narrow QRS group, where the changes were sustained and persisted at 2 and 3 years. The long-term death rate from HF was lower in the group with narrow than in the group with wide QRS complex (P = 0.04; log-rank test).
Conclusions: CRT confers considerable long-term clinical, functional, and survival benefits in patients presenting with HF and narrow QRS, not preselected by echocardiographic criteria of dyssynchrony. Caution is advised before denying CRT to these patients on the basis of QRS width only.