Low dose azaribine in the treatment of psoriasis

Thirteen patients with severe psoriasis were treated with low dose azaribine (125 mg/kg/day) for 8-week periods. Two patients with generalized pustular psoriasis and four patients with psoriatic arthritis had a good to excellent response. Severe neurotoxicity occurred in four patients, requiring lowering of the dose in three and discontinuance of the drug in one patient. Because of these results, azaribine at 125 mg/kg/day cannot be recommended for plaque-type psoriasis, though it is very effective against generahzed pustular psoriasis and psoriatic arthritis. Of the eleven patients with plaque psoriasis, seven had a good or excellent response initially but subsequently relapsed while on therapy; the other four patients failed to respond to the medication.     

Oral Loading with Propafenone: A Placebo-Controlled Study in Elderly and Nonelderly Patients with Recent Onset Atrial Fibrillation

The efficacy and safety of propafenone as an oral loading dose (600-mg single oral dose) in converting recent-onset atrial fibrillation (≤ 7 days duration) to sinus rhythm were evaluated in a single-blind, placebo-controlled study according to patients' age. Overall, 240 hospitalized patients, NYHA Class ≤ 2 without signs or symptoms of heart failure were enrolled: among patients aged ≤ 60 years, 55 were allocated to propafenone treatment and 59 to placebo, respectively, and among patients aged > 60 years, 64 were allocated to propafenone treatment and 62 to placebo, respectively. Results: In each age group, the likelihood of conversion to sinus rhythm was significantly greater after propafenone compared with plocebo at 3 and 8 hours. For patients aged ≤ 60 years, corresponding odd ratios were 3.78 (95% CI = 1.80–7.92, P = 0.04) at 3 hours and 4.74 (95% CI = 2.12–10.54, P = 0.02) at 8 hours; for patients aged > 60 years odd ratios were 5.03 (95% CI = 2.08–12.12, P = 0.02) at 3 hours and 6.75 (95% CI = 3.28–73.86, P = 0.01) at 8 hours, respectively. Logistic regression analysis showed that conversion to sinus rhythm within 3 hours was predicted by age ≤ 60 years (P = 0.0064) and by propafenone treatment (P < 0.0001), and conversion to sinus rhythm within 8 hours was predicted by age ≤ 60 years (P = 0.0467) and by propafenone treatment (P < 0.0001). The occurrence of adverse effects was observed in 14%-16% of propafenone treated patients and in 8% of placebo treated patients without significant differences according to age. In conclusion, in patients with recent-onset atrial fibrillation without signs of heart failure, propafenone as a single oral loading dose is effective. It is also effective in selected elderly subjects with a favorable safety profile. Moreover, spontaneous conversion to sinus rhythm appears to occur less frequently in elderly patients.     

Natural and Unnatural History of Patients with Severe Carotid Sinus Hypersensitivity: A Preliminary Study

Natural history of patients with symptomatic severe carotid sinus hypersensitivity is not clearly known. In order to evaluate the effectiveness of pacing therapy in these patients we performed a randomized treatment/no-treatment prospective study in 35 patients. They were randomly assigned to two groups: 19 patients received no therapy, 16 patients received a VVI (# 11) or DDD (#) pacemaker implant. During the 8.4 ± 4.3 month follow-up period patients receiving no therapy had recurrence of syncope in 9 cases (47%) and minor symptoms in 13 (68%); at the 16th month, actuarial curve showed absence of syncope in 36% of patients and of any symptoms in 30%. During the 7.2 ±4.1 month follow-up period, the patients receiving the pacemaker implant had no recurence of syncope, minor symptoms in three (19%); at the 16th month, actuarial curve showed absence of syncope in 100% of patients and of any symptoms in 78%. During follow-up, 12 patients in no-treatment group received a pacemaker implant because of the recurrence of severe symptoms; successively they had a strong reduction of symptoms. In conclusion, this study definitively demonstrates that patients with severe symptomatic carotid sinus hypersensitivity had a high rate of recurrence of spontaneous symptoms and that in these patients cardiac pacing is a useful therapy.     

Non-muscle involvement in late-onset Glycogenosis II

Glycogenosis II (GSD II) is an autosomal recessive lysosomal storage disorder resulting from acid alpha-glucosidase deficiency, subsequent accumulation of glycogen in tissues, impairment of autophagic processes and progressive cardiac, motor and respiratory failure.The late-onset form is characterized by wide variability in residual enzyme activity, age of onset, rate of disease progression and phenotypical spectrum. Although the pathological process mainly affects the skeletal muscle, several other tissues may be involved in the course of the disease; therefore GSD II should be regarded as a multisystem disorder in which glycogen accumulation is present in skeletal and smooth muscle, heart, brain, liver, spleen, salivary glands, kidney and blood vessels.In this review, we briefly summarize the main non-muscle targets of the pathological process in late-onset GSD II.Further studies aimed at evaluating the extra-muscle involvement in this group of patients will help to better define clinical features and prognostic factors and to delineate the natural history of the disease.Key words: Glycogenosis II, GSDII, Pompe diseaseGlycogenosis II (GSD II; Pompe''s disease; OMIM entry # 232300) is a storage disorder resulting from a deficiency of acid alpha-glucosidase, which is the only enzyme able to process glycogen into lysosomes. Enzyme deficiency leads to accumulation of glycogen in muscles, lysosomal disruption and excess of autophagic vesicle buildup inside the myofibers, causing progressive cardiac, motor and respiratory failure (1).GSD II can be clinically divided into two main subtypes. The infantile form usually appears in the first month of life, presents with severe cardiac involvement and total deficiency of alpha-glucosidase activity (< 1% of normal controls), and progresses rapidly; the late-onset form is characterized by phenotypical variability even though the main findings are progressive muscle weakness and severe respiratory insufficiency (2, 3).Limb-girdle weakness is frequently the early sign of the late-onset disease. Patients usually report difficulty in walking and running, playing sports, climbing stairs or rising from a chair. Severe weakness may also be observed in paraspinal muscles and additional neuromuscular features may include scapular winging and distal contractures. Respiratory muscles are always involved with weakness of the diaphragm, intercostal and accessory muscles whereas the cardiac damage is usually less severe (2). Muscle weakness and limited movement, especially of the antigravity muscles, may lead to alterations of posture, severe scoliosis and lumbar hyperlordosis, which entail biomechanical disadvantages, muscle contractures and deformity in a vicious circle of progressive disability.Increasing evidence shows that systemic abnormalities are present in GSDII patients and several tissues other than muscles may be involved in the course of the disease; therefore GSD II should be regarded as a multisystem disorder in which glycogen accumulation is present in skeletal and smooth muscle, heart, liver, kidney, spleen, salivary glands, glial cells, brainstem nuclei, anterior horn cells of spinal cord and blood vessels (2).In this review we briefly summarize the non-skeletal muscle targets of the pathological process in late-onset GSD II.     

Periprocedural Management and In-Hospital Outcome of Patients with Indication for Oral Anticoagulation Undergoing Coronary Artery Stenting

Purpose: In patients on oral anticoagulation (OAC) undergoing coronary stenting (PCI-S), procedural management and in-hospital outcome have never been specifically and prospectively investigated. Also, the contribution of early bleeding to the relevant hemorrhagic rate reported at follow-up with triple therapy of OAC, aspirin, and clopidogrel is largely unknown.
Methods: Consecutive patients with indication for OAC undergoing PCI-S at 5 centers were enrolled and prospectively evaluated.
Results: Out of 3410 patients undergoing PCI-S in the study period, indication for OAC was present in 4.8%. Femoral approach and bare metal stents were the most frequently used. During PCI-S, OAC was continued in about 30% of patients, whereas in about 20% heparin bridging was carried out. Glycoprotein IIb/IIIa inhibitors were rarely used (11%), whereas a standard bolus of unfractionated heparin was given in 93% of cases. Major adverse cardiovascular events (MACE) occurred in 4.8% of patients and major bleeding in 4.3%. No predictors of MACE or bleeding were identified, although the femoral approach was of borderline significance for major bleeding (OR 4.6, 95% CI 1.0–20.8; P = 0.05). A history of previous hemorrhage (OR 5.3, 95% CI 1.6–18.1; P = 0.007) predicted Carbofilm™-coated stent implantation.
Conclusions: A limited, albeit clinically relevant, proportion of patients undergoing PCI-S has indication for OAC. Procedural management appears not substantially different from that of common patients. In-hospital major bleeding is relevant and should be taken into account when evaluating the overall hemorrhagic rate at a medium- to long-term follow-up.     

Accuracy of Swabs, Tissue Specimens, and Lead Samples in Diagnosis of Cardiac Rhythm Management Device Infections

Aims: Pacemaker and implantable-cardioverter defibrillator lead infections widely increased with consequent need to accurately recognize responsible bacteria.
Methods: Between May 2003 and December 2007, we extracted 118 leads, 104 (87.3%) due to infections (sepsis, lead-associated endocarditis, pocket infection) or chronic draining sinus (with negative local bacteriological analyses). Swabs and tissue specimens from pocket and fragments of pin and tip of each extracted lead were obtained during extraction and sent for bacteriological examination.
Results: Cultures from explanted lead pins returned positive results in 100% of the cases presenting with local infections and in 92.5% of those with chronic draining sinus. In cases of sepsis, positive results of blood samples are less common than lead samples (58.3 vs 86.7, P = 0.02), the latter being more sensitive for infection diagnosis. Concordance between bacterial isolates from pocket and lead is quite low, approaching 45%, seemingly due to contamination effect. Concordance between isolates within the lead (pin and tip) is quite high, close to 70%, reflecting a more accurate expression of the real infection. In cases of sepsis, concordance between lead and blood samples, and mainly from tip and blood, is very high, resembling 80–85%; consequently bacterial isolates from the lead, particularly from lead tip, are clearly associated with clinical infections.
Conclusions: Our results strongly support the hypothesis that chronic draining sinus is often sustained by infection. Moreover, diagnostic accuracy of lead samples is higher not only than swabs and tissue samples, but also than blood samples to confirm an infection and to guide effective therapy.     

Automatic Management of Left Ventricular Stimulation: Hints for Technologic Improvement

Background: We used a cardiac resynchronization therapy defibrillator device with an algorithm for automatic verification of left ventricular (LV) stimulation to understand LV threshold variability, such as to provide hints to program the algorithm features. We also evaluated the algorithm performance over long term, and tested a stimulation setting to achieve 99% effective stimulation while maximizing device longevity. Methods: The LV output was programmed as threshold + 0.5 V; the upper limit of LV output adjustment was 6 V at programmed pulse width. The algorithm is insensitive to the strength of the pacing pulse, thus pulse width was conveniently programmed to minimize the use of voltage multipliers in all the patients. Follow‐ups occurred at 1 month, then every 3 months, for clinical assessment and manual threshold verification. The efficacy of this programming at long term was also evaluated by Holter validation of LV stimulation. Results: Twenty patients were followed for 14 ± 5 months (6–21). LV threshold showed no changes in 97% of consecutive days, whereas a 0.5‐V and 1‐V increase occurred, respectively, in 2.3% and 0.6%. Maximum variability of LV threshold was ≤0.5 V during 90% of the follow‐up period. Our programming of LV output provided 99–100% effective stimulation in 18 of 20 patients, and 90% efficacy in two patients because of missed threshold measurements. A 25% increase of device longevity can be expected by this programming. Conclusions: LV threshold variability is truly modest. Daily update of LV threshold should be improved to ensure 100% LV stimulation by a threshold + 0.5 V safety margin. Device longevity is maximized when LV stimulation occurs below battery voltage.     

Coexpression of CD69 and HLADR activation markers on synovial fluid T lymphocytes of patients affected by rheumatoid arthritis: a three-colour cytometric analysis.

The aim of the present study was to evaluate the coexpression of very early (CD69), early (CD25) and late (HLADR) antigens and to analyse the mean fluorescence intensity (MFI) of such activation markers on synovial fluid (SF) and peripheral blood (PB) lymphocytes of patients affected by rheumatoid arthritis (RA) and other types of chronic synovitis (OCS). A three colour cytometric analysis was performed using a peridinin chlorophyll protein conjugated anti-CD3 antibody in combination with fluorescein isothiocyanate or phycoerythrin labelled anti-CD69, anti-HLADR, anti-CD25 monoclonal antibodies (mAbs). A T cell gating method was utilized, so that three sets of bivariant dot plot quadrant displays were obtained (CD69/HLADR, CD69/CD25, CD25/HLADR). A large percentage of SF T lymphocytes in RA showed the coexpression of very early and late activation antigens (CD3 + CD69 + HLADR +), whereas CD3 + CD69 + CD25 + bearing cells and CD3 + CD25 + HLADR + lymphocytes were only a small percentage. Similar results were obtained in patients with OCS, although to a lesser extent. No statistically significant differences in MFI of CD69 and HLADR positive SF T cells between RA and OCS were observed. The CD69 + CD25-HLADR + T cell subset is the most commonly represented in the synovial environment, among those we have evaluated; this phenotype may be characteristic of chronic inflammatory arthritis.