Characteristics and management of generalized pustular psoriasis (GPP): Experience from the Central and Eastern Europe (CEE) GPP Expert Network.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, inflammatory skin disease characterized by widespread eruption of sterile pustules with or without systemic symptoms. OBJECTIVES: This study aimed to describe the demographics of patients with GPP in Central and Eastern Europe (CEE), present the clinical characteristics of individual GPP flares and explore the current treatment landscape. METHODS: Patient demographics were collected at the times of last observation and previous treatment. Characteristics of a patient's last (most recent) and most severe (from all documented episodes) flare were provided at clinician's discretion. RESULTS: Fifty-eight patients were recruited from 12 centres in nine CEE countries; median (range) age was 61 (16-92) years and 60.3% (35 out of 58) were female. The most common comorbidities were hypertension (43.1% [25 out of 58]) and hyperlipidaemia (32.8% [19 out of 58]). Thirty-four patients (58.6%) presented with concomitant plaque psoriasis before or during the course of GPP. Data from two separate flares were recorded in 26 individuals; in 32 patients, the most recent flare was reported as the most severe. Over 90% of patients with a flare episode classified as most severe by clinicians were hospitalized, with >75% of these individuals having a Generalized Pustular Psoriasis Physician Global Assessment (GPPGA) total score of 3 or 4. Systemic symptoms were more common in patients with a GPPGA score of 3 or 4 but were also manifest in individuals with a GPPGA score ≤2. A significant correlation was observed between a combined systemic disease score of clinical and laboratory features and both GPPGA total score (r = 0.385, p < 0.001) and GPPGA pustulation subscore (r = 0.305, p < 0.05). CONCLUSIONS: Considerable heterogeneity in the presentation of GPP flares was observed, both between patients and within-patient. All GPP flares were associated with a significant clinical burden, highlighting the unmet need for accurate and early diagnosis.

Autologous platelet-rich plasma for treatment of venous leg ulcers: a prospective controlled study.

Venous leg ulcers (VLUs) are chronic difficult-to-treat wounds which affect around 1-2% of the world population. Conventional methods for treatment such as mechanical debridement, occlusive dressings and local antibiotics in case of infection, often lack effectiveness. Autologous platelet-rich plasma (PRP) is an alternative method in the treatment of chronic wounds. PRP contains inflammatory mediators, growth factors, and cytokines that modulate the wound microenvironment to create a better chance for healing. The aim of this prospective clinical study was to evaluate the efficacy of intralesional injection of PRP in the management of VLUs. This study included 23 patients with VLUs. For each patient, two ulcers located in the same anatomical zone and at the same clinical stage were selected. One was treated with a single application of autologous PRP. The other ulcer was used as a control and was treated by conventional methods. The size of the ulcers was assessed at baseline (visit 0), 15 days (visit 1) and 30 days after the procedure (visit 2). Results showed a significant reduction of the size of the ulcer both in the group treated with PRP (mean surface 1368.2 mm2 at visit 0 and 596.3 mm2 at visit 2) and in the control group (mean surface 880.3 mm2 at visit 0 and 582.8 mm2 at visit 2). Statistical analysis showed a significant change in the size of the ulcer between visit 0 and visit 2 in both groups (p less than 0.0001). The application of PRP in difficult-to-treat venous leg ulcers may be a promising new method for therapy of this condition. The results of this study correlate with the data from the majority of previous studies and confirm the effectiveness of PRP. Nevertheless further research in the area is needed to evaluate the therapeutic significance of the method and eventually show its superiority to conventional treatments in larger cohorts.

[THE EFFECT OF SEROTONIN ON THE INOTROPIC FUNCTION OF MYOCARDIUM OF THE LEFT VENTRICLE OF IMMATURE SPONTANEOUSLY HYPERTENSIVE RATS].

The mechanisms of the serotonin effect on the inotropic function of the myocardium of the left ventricle of immature spontaneously hypertensive rats (SHR) are unexplored. It was found that systolic arterial blood pressure of 5-6 weeks SHR rats is 147.5 mm Hg, which is statistically significantly higher (more than 25 mm Hg) than in the same age of normotensive control Wistar- Kyoto rats. The weight of the heart, of the left ventricle myocardium, of the ventricular septum, of the aorta and the force of contraction of the left ventricle of 5-6-week-old SHR rats are increased significantly compared with the control. 0.1 pM serotonin increases and 1.0 pM and 10.0 AM serotonin reduce the force of contraction of the left ventricular myocardium in hypertensive rats, but there is a dose-dependent increase of the force of contraction in the control. Serotonin reduces the time of contraction of the myocardium of the left ventricular of SHR rats, these reactions are less pronounced as compared to the control.

Comparative analysis of serological activity of non-structural protein (NS1) from tick-borne encephalitis virus and its analog expressed in bacterial cells.

By means of immunoaffinity chromatography and expression of the gene in Escherichia coli, non-structural glycoprotein NS1 of tick-borne encephalitis virus (TBEV) and its recombinant analog were prepared. Antisera against these proteins were obtained by hyperimmunisation of rabbits. The antisera were tested by means of complement fixation, agar diffusion, hemagglutination inhibition and virus neutralization. Although both antisera are reacted with natural antigen, the recombinant analog of NS1 did not bind antibodies against natural protein in complement fixation and immunoprecipitation. Nevertheless the NS1 analog was rather active in ELISA. Neither the natural nor the recombinant protein protected experimental animals from lethal virus infection. A contamination of natural NS1 antigen with small amounts of structural glycoprotein E may be responsible for both antibody formation and virus neutralization. This can be relevant for the design of a subunit vaccine.

The effect of flumazenil on visual event-related potentials of clinically non-encephalopathic patients with cirrhosis.

The effects of flumazenil on the latencies and amplitudes of visual event-related potentials (ERPs), number-connection test (NCT) and visual and auditory reaction times (VRT and ART) were evaluated in ten patients with cirrhosis without clinically overt encephalopathy (HE). Delayed latencies of the ERP component P3a and/or P3b were found in three patients and the time to complete NCT was prolonged in two other patients. Changes in the latencies and amplitudes of the ERP components (N200, P3a and P3b) during 40 min following infusion of flumazenil (1 mg) and placebo were similar. Results of the three psychometric tests did not change significantly after either flumazenil or placebo infusion. Eight of the ten patients felt more alert for several minutes after the administration of flumazenil, whereas no patient experienced any change of perception after infusion of placebo. Prolongation of the latencies of P3a and P3b may be a component of the syndrome of subclinical HE. However, these neuro-electrophysiological abnormalities in cirrhotic patients may not be attributable to increased brain levels of natural benzodiazepines.

Visual event-related potentials in cirrhotic patients without overt encephalopathy.

UNLABELLED: Ambulant patients with cirrhosis and no clinical evidence of encephalopathy were screened for impaired brain function by neuroelectrophysiological testing dependent on cognitive function. Infrequent large checkerboard visual stimuli were randomly interleaved with frequent small ones to elicit P300 event-related potentials (ERPs). Three ERP components, N200, P3a and P3b, were derived from the electroencephalogram (EEG) by computer averaging. The use of 10% contrast and a minimum of four precisely placed scalp electrodes were found to be necessary for optimal separation of ERPs from sensory evoked potentials. Visual ERPs, onset/offset and pattern-reversal visual evoked potentials (VEPs), the spontaneous EEG and the time taken to complete a standard number connection test (NCT) were obtained from 20 normal adult subjects and 19 age-matched patients with histologically-confirmed cirrhosis and no clinical evidence encephalopathy. The latencies and amplitudes of evoked potentials and the alpha rhythm of the EEG were determined. In 6 of the 19 patients the latencies of P3a and/or P3b exceeded the corresponding mean for controls + 2 standard deviations of that mean. In 4 other patients the NCT was prolonged. In all of the patients the N200, VEPs and alpha rhythm of the EEG were normal. IN CONCLUSION: (i) Optimal isolation of ERPs is critically dependent on stimulus contrast and electrode placement; (ii) ERPs appear to be more sensitive than primary sensory evoked potentials or the EEG in detecting impaired brain neuroelectrophysiological function; and (iii) Cirrhotic patients without overt encephalopathy in whom P3a and/or P3b latencies are prolonged may have subclinical hepatic encephalopathy.

Visual event-related potentials in cirrhotic patients without overt encephalopathy: the effects of flumazenil.

The P300 complex was derived from the electroencephalogram (EEG) as subjects mentally counted infrequent large checkerboard visual stimuli, presented randomly among frequent small checkerboard stimuli. Use of low contrast (10%) stimuli and four midline scalp electrodes, facilitated separation of cognitive and sensory components and enabled the P300 complex to be resolved into three distinct components--N200, P3a, and P3b. In 20 healthy adult subjects normative data were established and the P3a and P3b components were shown to depend on cognitive function. In 19 age-matched cirrhotic patients without overt hepatic encephalopathy (HE) the EEG and visual evoked potentials (VEPs) were normal, but latencies of P3a and/or P3b were prolonged in 9. Prolonged latencies were not associated with an abnormal number connection test. Ten additional age-matched cirrhotic patients without overt HE, who were alcohol, drug, and caffeine free, were randomized to receive flumazenil (1 mg) and placebo intravenously, double-blind. After flumazenil or placebo, latencies of P3a and P3b and psychometric test results did not change significantly. These findings suggest that in cirrhotic patients without overt HE (i) impaired cognitive sensory function may occur in the absence of abnormalities of a standard psychometric test, the EEG, or VEPs, and (ii) increased latencies of P3a and P3b may constitute a component of subclinical HE, which is not mediated by increased brain levels of central benzodiazepine receptor agonist ligands.