The cost of hospital-related care of patients with psoriasis in Italy based on the AISP study

The objective of this study was to assess the cost of caring for patients with psoriasis in Italy according to the AISP study (Associazione Italiana Studi Psoriasi or Italian Association for Studies on Psoriasis), involving 104 university and hospital centres and 7992 patients in 1994. The mean yearly cost of care for a single patient was calculated at 905 Euros. Hospitalization accounted for more than four-fifths of the costs, therapy for about one-eighth (systemic therapies were the most expensive) and office visits and day hospitals for the remainder. In our study series less than 20% of patients accounted for more than 90% of the total costs.     

FAT ARMS,OBESITY AND CHOICE OF BLOOD PRESSURE CUFF SIZE IN DIABETIC PATIENTS

SUMMARY Four hundred consecutive diabetic patients had their mid-arm circumference (AC) measured and body mass index (BMI) calculated to determine the proportion of an unselected clinic group who would require a larger than standard adult blood pressure (BP) cuff and whether or not BMI could be used to predict AC and hence choice of appropriate BP cuff size. More than 75% of both men and women had an AC ≥29cm, justifying a larger than standard adult cuff for their BP measurement. When patients were classified according to their BMI, at least 80% with a BMI ≥30 and more than 70% with a BMI of 25-29 had a measured AC ≥29cm, while less than a third of patients with a BMI ≥25 had an AC ≥29cm. These results indicate that, in a diabetic clinic, most patients with a BMI ≥25 are likely to require an alternative adult BP cuff if their blood pressure is to be measured precisely.     

Death due to an implantable cardioverter defibrillator

Inappropriate therapy due to noise oversensing caused a true ventricular fibrillation (VF) and death of a patient. A 49-year-old patient with a history of dilated cardiomyopathy received a double-chamber implantable cardioverter defibrillator (ICD) in 1991 for a sustained inducible ventricular tachycardia (VT). One appropriate shock delivered in 1994 terminated an episode of VT. The generator was replaced in 1995 and in 2000, and was connected to the initial leads. Three months after the second replacement, the patient received six consecutive shocks related to detection of noise interpreted as VF. Unfortunately, the sixth shock triggered a true VF, which was not treated due to end of the therapeutic sequence, and the patient died. The causes of the dysfunction are discussed.     

Decreased nocturnal standard deviation of averaged NN intervals. An independent marker to identify patients at risk in the Brugada Syndrome.

AIMS: Risk-stratification of asymptomatic Brugada Syndrome (BS) patients remains a key-issue. A typical spontaneous BS-ECG pattern and ventricular tachycardia (VT)/ventricular fibrillation (VF) inducibility are two recognized risk markers. The aim of the study was to identify additional risk markers in asymptomatic BS. METHODS AND RESULTS: We have compared Holter recordings in symptomatic and in asymptomatic patients with BS. Heart rate variability (HRV), QT-interval rate-dependence and ST-segment elevation (ST-SE) were analysed. The study population included 47 BS patients (M=36, mean age=45+/-13 years) with a malignant ventricular arrhythmia in 11 cases, an unexplained syncope in 10 cases and no symptoms in the remaining 26 cases. A typical spontaneous BS-ECG was present in 21 cases and a drug-induced BS-ECG in 26 cases. A downward trend of the time domain variables of HRV was observed. During the nocturnal period, standard deviation (SD) of the 5min averaged NN intervals (SDANN) (46+/-13 vs 57+/-18ms, P=0.02) and ultra low frequency component (3287+/-2312 vs 5030+/-3270 ms(2), P=0.04) were significantly lower in symptomatic versus asymptomatic patients. In contrast, no difference was found in QT-interval rate dependence and in ST-SE. At multivariate logistic regression, VT/VF inducibility, typical spontaneous BS-ECG and a decreased nocturnal SDANN were associated with arrhythmic events (P=0.003). CONCLUSIONS: A decreased nocturnal SDANN was an independent marker of arrhythmic events in these BS patients.     

A cytokine receptor gene cluster in the X-Y pseudoautosomal region?

The receptors for interleukin-3 (IL-3), IL-5, and granulocyte- macrophage colony-stimulating factor (GM-CSF) are heterodimers comprised of ligand specific alpha chains and a common beta chain. The genes encoding the IL-5 receptor alpha chain and the common beta chain reside on chromosome 3 and 22 respectively, while the GM-CSF receptor alpha chain gene (CSF2RA) has been mapped to the pseudoautosomal region (PAR) of the sex chromosomes, which is a 2.6-Mb stretch of homologous sequence at the tips of the short arms within which a single obligatory recombination occurs during male meiosis. We have mapped the gene encoding the IL-3 receptor alpha chain (IL3RA) to the sex chromosomes by polymerase chain reaction (PCR) analysis of human-mouse or human- chinese hamster cell hybrids, and to Yp13.3 and Xp22.3 using fluorescence in situ hybridization. To explore the possibility that IL3RA is located within the pseudoautosomal region we screened the Centre d'Etude du Polymorphisme Humain (CEPH) pedigrees for an informative-restriction fragment-length polymorphism (RFLP) that showed male meiotic recombination. Two informative CEPH pedigrees were identified that displayed this phenomenon, confirming the psuedoautosomal location of IL3RA. Using long-range restriction mapping we have found that IL3RA maps to the same 190-kb restriction fragment as CSF2RA, suggesting that a cytokine receptor gene cluster may reside in the PAR.     

Procalcitonin (PCT) and C-reactive Protein (CRP) as severe systemic infection markers in febrile neutropenic adults

Background  

Procalcitonin (PCT) is an inflammatory marker that has been used as indicator of severe bacterial infection. We evaluated the concentrations of PCT as a marker for systemic infection compared to C-reactive protein (CRP) in patients neutropenic febrile.     

Identification of residues in the first and fourth helices of human granulocyte-macrophage colony-stimulating factor involved in biologic activity and in binding to the alpha- and beta-chains of its receptor

Residues within the first and fourth helices of human granulocyte- macrophage colony-stimulating factor (hGM-CSF) were analyzed for their role in biologic activity and interaction with the alpha- and beta- chains of the hGM-CSF receptor. Within the first helix substitution of the surface residues Glu14, Asn17, Gln20, Arg23, Arg24, and Asn27 or the buried residues Ala18, Leu25, and Leu28 did not significantly impair bioactivity or receptor binding. Substitutions at the buried residues Ala22 and Leu26 had intermediate bioactivity. However, substitutions of the surface residue Glu21 or the buried residue Ile19 reduced the relative bioactivity of the analogues to as little as 0.45% and 0.3%, respectively. Substitution of the charged surface residues of the fourth helix showed that substitution at Glu104, Lys107, and Lys111 had no significant effect on bioactivity, but substitution at Glu108 and Asp112 reduced the potency of the analogues to 34% and 7%, respectively. Receptor binding studies showed that, whereas Glu21 is the critical residue for binding to the hGM-CSF-receptor beta-chain, Asp112 is likely to be involved in binding to the GM-CSF-receptor alpha- chain. These results establish the relative contribution of residues in the first and fourth helices for GM-CSF bioactivity and receptor binding, and support a model where the fourth helix of GM-CSF interacts with the alpha-chain, and the first helix with the beta-chain of the GM- CSF receptor.     

Inhibition of proliferation and induction of apoptosis in juvenile myelomonocytic leukemic cells by the granulocyte-macrophage colony- stimulating factor analogue E21R

Juvenile myelomonocytic leukemia (JMML) is a malignancy that almost inevitably leads to death before adulthood. Chemotherapy has given disappointing results and a substantial number of patients relapse after bone marrow transplantation. A salient feature of this disease is that the JMML cells produce granulocyte-macrophage colony-stimulating factor (GM-CSF) spontaneously and survive and proliferate without exogeneous GM-CSF. Furthermore, JMML cells are hypersensitive to GM-CSF with addition of this cytokine leading to enhanced proliferation. We have recently generated a human GM-CSF analogue, E21R, that acts as a complete and selective GM-CSF receptor antagonist. We have now tested this molecule as a potential new agent to control the leukemic cell load in JMML with particular emphasis on its role in JMML cell survival. We found that E21R inhibited the spontaneous growth of JMML cells in vitro and caused their apoptosis in a dose- and time-dependent manner in seven of seven cases. In contrast, neither a neutralizing anti-GM-CSF monoclonal antibody (MoAb) nor a selective interleukin-1 (IL-1) receptor antagonist affected JMML cell survival. Furthermore, the apoptotic effect of E21R was seen even in the presence of interleukin-1 beta and tumor necrosis factor-alpha, which have also been implicated in the pathogenesis of JMML. The inhibitory effects of E21R on JMML cell growth and viability offer a novel approach to therapy in this lethal childhood leukemia.     

Characteristics and prognosis of ventricular arrhythmia in arrhythmogenic right ventricular dysplasia

The authors report their findings in 47 cases of ventricular arrhythmias due to arrhythmogenic dysplasia. The 47 patients were selected on the presence of ventricular tachycardia or fibrillation associated with dysplasia affecting selectively (44/47) or predominantly (3/47) the right ventricle at angiography. In this series males were predominant (38/47, 81 p. 100), familial incidence was high (13/47, 28 p. 100) and ECG abnormalities were constant. Most of the dysrhythmias (40/47) consisted of sustained ventricular tachycardia (VT) with left bundle branch block pattern (96 p. 100), occurring at the rate of 1.6 per patient on average and seldom with extreme axial deviation, as seen in post-infarction VT or VT associated with cardiomyopathy. The QRS complex was slightly prolonged (151 +/- 28 ms) and of high amplitude (2.5 +/- 1 mV on a VR, a VL and a VF leads), these values being intermediate between those of mild VT bursts and those of post-infarction or cardiomyopathy-related VT. The tachycardia was easily tippered by EP study, Intercritical Holter recordings showed frequent ventricular extrasystoles in the vast majority of cases; these were usually polymorphous and grouped into short bursts in one-half of the patients. On an 8.3 +/- 7 years' follow-up starting with the first attack of VT, it was found that only during the initial phase the spontaneous onset of VT was mediated by the adrenergic system (triggered by sports). Only 3 patients died during the follow-up period: one of ventricular fibrillation, 2 of right heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiac Effects of Chronic Oral Beta‐Blockade:

Background: Although well established on the sinus node, the effects of beta‐blockade on ventricular repolarization are still conflicting. The aim of the study was to investigate the effects of a chronic beta‐blockade on sinus node and repolarization parameters and their relationship. Methods: Sixteen healthy volunteers (10 males, mean age: 40 ± 6.7 years) were randomized to placebo or atenolol (100 mg). After 7 days, subjects were crossed over. Heart rate (HR) and HRV indices were calculated from long‐term ECG recordings separately during the day and at night, together with ventricular repolarization parameters (QT interval duration and QT rate‐dependence). Results: Mean R‐R intervals were significantly and consistently increased after atenolol (Day: 916 ± 103 ms vs. 712 ± 89 ms, and Night: 1149 ± 93 vs. 996 ± 125 ms). HRV changes under atenolol were also consistent, with a significant decrease in sympathovagal ratio. In contrast, atenolol only lowered diurnal QT rate‐dependence (0.123 ± 0.032 vs. 0.190 ± 0.065 on placebo, P < 0.001), but not the nocturnal pattern. After multivariate analysis QT rate‐dependence changes induced by atenolol were correlated with pretreatment QT/RR relation (r = 0.65, P < 0.01) but not with any HR or HRV parameters. Conclusions: In healthy subjects, repolarization changes following chronic beta‐blockade cannot be predicted by HR or HRV changes, but are dependent on pretreatment rate‐dependence. A.N.E. 2002;7(4):379–388