DEVELOPMENT OF ANTHRALIN SHORT-CONTACT THERAPY IN PSORIASIS: SURVEY OF PUBLISHED CLINICAL TRIALS

In a survey of clinical trials concerning the efficacy of short-contact therapy with anthralin in psoriasis vulgaris, focusing principally on methodologic issues, twenty-four papers published between January 1982 and December 1989, in English, French, and Italian, were selected. Nine of 24 papers reported on more than one trial, giving a total of 37 clinical trials to be evaluated. A great heterogeneity was evident in many aspects of the design and conduct of these trials, making pooling of results impossible. Most trials suffered from flaws in general methodologic aspects such as randomization and blinding. Limitations in general applicability of results were discussed with reference to the popular use of self-control design and selection of composite indexes (e.g., PASI) as an outcome variable. Published trials are not a reliable guide to clinical decisions concerning short-contact therapy, and some methodologic observations we made could be of general interest in designing clinical trials of psoriasis.     

Age-related changes of the 3'APOB-VNTR genotype pool in ageing cohorts

The analysis of seven different age cohorts (697 individuals from 10 to 109 years old) revealed age-related changes in the 3'APOB-VNTR genotype pool. By recoding the 3'APOB-VNTR alleles into three size-classes (small, S, 26–34 repeats; medium, M, 35–39 repeats; large, L, 41–55 repeats), an age-related convex trajectory of the frequency of SS homozygotes was found. The frequency of SS in the genotype pool increased from the group aged 10–19 years (3.06±1.74%) to that aged 40–49 years (8.51±4.07%). Then it declined reaching the minimum value in centenarians (1.58±0.90%). The observed trajectory is in agreement with that expected by assuming crossing of mortality curves relevant to subgroups of individuals having different genotypes.     

Neuroimaging in childhood arterial ischaemic stroke: evaluation of imaging modalities and aetiologies

Aim The aim of this study was to describe neuroimaging patterns associated with arterial ischaemic stroke (AIS) in childhood and to differentiate them according to stroke aetiology. Method Clinical and neuroimaging (acute and follow‐up) findings were analysed prospectively in 79 children (48 males, 31 females) aged 2 months to 15 years 8 months (median 5y 3mo) at the time of stroke by the Swiss Neuropaediatric Stroke Registry from 2000 to 2006. Results Stroke was confirmed in the acute period in 36 out of 41 children who underwent computed tomography, in 53 of 57 who underwent T2‐weighted magnetic resonance imaging (MRI) and in all 48 children who underwent diffusion‐weighted MRI. AIS occurred in the anterior cerebral artery (ACA) in 63 participants and in all cases was associated with lesions of the middle cerebral artery (MCA). The lesion was cortical–subcortical in 30 out of 63 children, cortical in 25 out of 63, and subcortical in 8 of 63 children. Among participants with AIS in the posterior circulation territory, the stroke was cortical–subcortical in 8 out of 16, cortical in 5 of 16, and thalamic in 3 out of 16 children. Interpretation AIS mainly involves the anterior circulation territory, with both the ACA and the MCA being affected. The classification of Ganesan is an appropriate population‐based classification for our Swiss cohort, but the neuroimaging pattern alone is insufficient to determine the aetiology of stroke in a paediatric population. The results show a poor correlation between lesion pattern and aetiology.     

Long-Lasting Catch-up Growth under Bio-Methionyl Growth Hormone Treatment in an Infant with Isolated Growth Hormone Deficiency Type 1A1

ABSTRACT. This case report concerns a 7-month-old infant with severe height retardation (–5.0 SD), typical growth hormone (GH)-deficient phenotype, and undetectable GH serum levels in response to three pharmacological stimuli. Diagnosis of isolated GH deficiency type 1A was confirmed by restriction endonuclease analysis of genomic DNA which pointed out GH-N gene deletion. The introduction of bio-methionyl-GH therapy in this patient was followed by a transient and clinically irrelevant appearance of low binding capacity GH antibodies as well as by a long-lasting catch-up growth (42.2 cm) which is continuing 44 months after beginning of treatment. This atypical pattern confirms that immune and growth response to exogenous GH in isolated GH deficiency 1A may be very heterogeneous.     

RECTAL PROLAPSE

One hundred and twenty-seven patients with complete rectal prolapse have been reviewed. The condition occurred more commonly in females than males (105 to 22), and at an older age in females (mean age 55 years compared with 40 years for males). Although the diagnosis is usually obvious, the importance of recognizing occult prolapse is stressed, especially in association with benign rectal ulcer, localized proctitis and colitis cystica profunda. Examination of the patient in the squatting position may assist in showing occult prolapse. Associated incontinence occurred in 33 patients (26%). Since 1971 the policy of this Unit has been to perform a Ripstein repair for complete rectal prolapse wherever possible. One hundred and two Ripstein repairs have now been performed. A minimum follow-up period of two years is available for 53 patients, of whom 50 (94%) have had their prolapse cured. Control of prolapse usually improves continence; however, seven (13%) remained incontinent despite surgery. The Ripstein. repair is strongly advocated as the most effective operation for cure of complete rectal prolapse.     

Malignancy: Changes in Circulating Immature and Mature Dendritic Cells During IL-2 Cancer Immunotherapy and Their Relation with Lymphocyte Increase and Clinical Response

Lymphocytosis is the main biomarker predicting the efficacy of subcutaneous IL-2 anticancer immunotherapy. In addition, it has been demonstrated the fundamental role of dendritic cells (DC) in the generation of an effective anticancer immunity. However, the relation between IL-2 and DC system needs to be further understood. This preliminary study was performed in an attempt to analyze changes in circulating DC during IL-2 cancer immunotherapy in relation to lymphocyte variations and clinical efficacy of treatment. The study included 20 metastatic renal cell cancer patients, who underwent subcutaneous low-dose IL-2 immunotherapy (6.000.000 IU/day for 6 days/week for 4 weeks). To evaluate DC, venous blood samples were collected before and after 2 weeks of IL-2 injections, corresponding to the period of maximum lymphocytosis. Immature (CD123(+) ) and mature (CD11c(+) ) DC were measured by FACS and monoclonal antibodies. IL-2 induced a significant increase in the mean number of circulating mature DC, whereas no substantial change occurred in immature DC mean number. The increase in mature DC was associated with a control of disease, whereas no rise was observed in patients who had progressed on IL-2 immunotherapy. Moreover, the increase in mature DC mean number was significantly higher in patients showing evident lymphocytosis, with lymphocyte enhancement greater than 1000 cells/mmc, than in patients with less pronounced lymphocytosis, even though no significant correlation was seen in between mature DC and lymphocyte increase. This preliminary study would suggest that IL-2 may stimulate DC system and that the clinical anticancer efficacy of IL-2 is associated with the increase in circulating mature DC, which could be considered as a new favourable biomarker during IL-2 immunotherapy.     

High Energy Transcatheter Cardioversion for Chronic, Poorly Tolerated Atrial Fibrillation

Between August 1991 and May 1993, 14 patients affected by chronic, poorly tolerated atrial fibrillation (AF) were submitted to high energy transcatheter Cardioversion. Mean duration of AF was 27.4 ± 45.1 months. In nine patients (56%), AF lasted for > 1 year. All patients had underlying heart disease, with a mean LVEF of 45.2%± 11.8% and a NYHA Class ≥ II. Previously, a mean of 2.9 ± 1.3 patients failed external electrical Cardioversion, with and without antiarrhythmics, have been attempted. Transcatheter conversion was performed by pulling the His-bundle catheter back in the right atrial cavity until no His bundle activity was recorded on distal poles, and then delivering the shock between a proximal electrode (cathode) and a back plate (anode). In all patients, transcatheter conversion restored sinus rhythm. Transient complete atrioventricular (AV) block was observed in four patients (28%), and treated by prophylactic temporary pacing. At 1 year, seven patients (50%) were still in sinus rhythm. In this series, only younger age could be related to AF recurrence (46.1 ± 10.8 vs 63.4 ± 6.8 years, P ≤ 0.004), even if prophylaxis with amiodarone showed a positive trend versus sinus rhythm maintenance (71 % vs 14%, P = NS). In conclusion, high energy transcatheter Cardioversion is a safe and effective method of restoring sinus rhythm in patients with chronic, poorly tolerated AF. In these patients, high energy transcatheter Cardioversion could be considered as an alternative to AV node ablation techniques, avoiding pacemaker implant and embolic risk. Larger studies are needed to determine better patient selection and delineate drug strategy after the procedure.