Psoriasis confined strictly to vitiligo areas – a Koebner‐like phenomenon?

Vitiligo and psoriasis are both common skin disorders. However, psoriasis strictly confined to pre-existing vitiligo areas is rare and suggests a causal relationship. We report here on two patients with a strict anatomical colocalization of vitiligo and psoriasis. The histopathological examinations showed typical changes for both diseases together with a dense infiltrate of CD4+ and CD8+ T cells. By immunohistochemistry, intracytoplasmatic granzyme B and tumour necrosis factor alpha (TNF-alpha) were detected within the T-cell population, suggesting the functional activity of these cells and the creation of a local T helper 1 (Th1)-cytokine milieu. Additionally, in one patient we could identify anti-melanocytic T cells by tetramer staining and enzyme-linked immunospot (ELISPOT) analysis. These skin-infiltrating lymphocytes might trigger, by the local production of Th-1 cytokines such as TNF-alpha and interferon-gamma (IFN-gamma), the eruption of psoriatic plaques in patients with a genetic predisposition for psoriasis.     

Randomised double blind placebo controlled trial of prednisolone in children admitted to hospital with respiratory syncytial virus bronchiolitis

BACKGROUND: Experimental and clinical evidence suggests that respiratory syncytial virus (RSV) bronchiolitis is an immune mediated disease. Corticosteroids might therefore be effective in the treatment of RSV bronchiolitis. METHODS: A randomised double blind trial was conducted in children up to two years of age admitted to hospital with RSV bronchiolitis to compare prednisolone (1 mg/ kg/day orally for seven days) with placebo. Variables used for the efficacy analysis were a daily symptom score and the length of time in hospital in the non- ventilated patients, and the duration of mechanical ventilation and the length of time in hospital in the ventilated patients. RESULTS: Fifty four patients were included in the trial, 40 of whom were non- ventilated (20 in each group) and 14 were ventilated (seven in each group). During the first three days of treatment the symptom score decreased significantly faster in the prednisolone group than in the placebo group (mean (SE) decrease -1.2 (0.2) points/day versus -0.6 (0.2) points/day; mean (95% confidence interval (CI)) for difference = - 0.6 (-0.1 to -1.2); p = 0.02). The mean duration of hospital stay of all 40 non-ventilated patients was not significantly different between the two groups. In the ventilated patients the duration of mechanical ventilation was not significantly different, but the length of time in hospital was six days shorter in the prednisolone group than in the placebo group (mean (SE) 11.0 (0.7) versus 17.0 (2.0) days; mean (95% CI) difference = 7.0 (1.8 to 10.2) days; p < 0.01). CONCLUSIONS: These results suggest that prednisolone may be effective in accelerating the clinical recovery of children admitted to hospital with RSV bronchiolitis.


     

HIV-antibody seroconversions in Dutch haemophiliacs using heat-treated and non heat-treated coagulation factor concentrates

A national multicentre study was performed to investigate the effects of donorselection and the use of heat-treated plasma products on seroconversion to HIV in 157 Dutch haemophiliacs. All patients included in the study were seronegative for HIV antibodies in 1983. Thirteen percent (20/157) seroconverted between 1983 and 1986. Nineteen of 20 seroconversions could be related to the use of non heat-treated products in the year preceding HIV antibody seroconversion. One seroconversion occurred in a person using heat-treated non donor screened product. Seroconversion rate decreased as a result of the policy to discourage high risk blood donors and no seroconversions were observed following the introduction of donor screening in 1985.     

Circannual variation in lymphocyte subsets, revisited

BACKGROUND: Circadian and circannual variations in lymphocyte subsets, especially CD8+ T-lymphocytes, have been reported. This study focuses on CD4+ T-lymphocyte seasonal variation over a 6-year 8-month period. STUDY DESIGN AND METHODS: Lymphocyte subsets were quantitated monthly for four healthy individuals from 1986 through 1992 as part of a flow cytometry quality-control program. RESULTS: In general, there were no significant seasonal changes in the total number of white cells or in total lymphocyte counts. The absolute numbers of CD4+ T-lymphocytes were lowest in summer when the CD8+ T-lymphocytes were highest. Mean CD4+ T-lymphocyte counts were 846, 967, 618, and 695 per microL for Subjects 1 through 4, respectively, in winter and 432, 670, 355, and 766 per microL, respectively, in summer. Two healthy subjects had CD4+ T-lymphocyte counts lower than 300 per microL on one or more occasions during the study period. In three of the four subjects, the percentage of B-lymphocytes in winter was almost double that in summer. In one of the four subjects, no circannual rhythm was observed in these lymphocyte subpopulations. CONCLUSION: The seasonal variation in CD4+ T- lymphocyte counts demonstrated in three healthy individuals over almost 7 years is again of interest in light of renewed consideration of using surrogate tests, such as CD4+ T-lymphocyte counts, to screen for AIDS- like diseases that may be in the blood supply.     

A rapid microagglutination test for the diagnosis of Legionella pneumophila (serogroup 1) infection

A rapid microagglutination test has been developed which can be performed in 30 minutes. Ninety-seven percent of 96 patients diagnosed as having Legionella pneumophila (serogroup 1) infection by indirect immunofluorescence were also detected by the rapid microagglutination test.     

Studies on the origin of redox enzymes in seminal plasma and their relationship with results of in-vitro fertilization

Glutathione (GSH), GSH peroxidase (GPX), GSH reductase (GRD), superoxide dismutase (SOD) and catalase-like enzyme activity were quantified in seminal plasma from normozoospermic patients, men with known distal ductal occlusion, proven fathers and male partners of couples receiving in-vitro fertilization (IVF) treatment for both male and female causes. Glutathione was non-detectable (< 2.5 microM) in seminal plasma. None of the enzyme activities per unit volume were lower in semen from vasectomized men, suggesting that they did not originate substantially from the testis or epididymis. The strongest relationships between enzyme activities and accessory gland markers were between zinc and GRD (r = 0.678), SOD (r = 0.602) and GPX (r = 0.548), suggesting a largely prostatic origin of these enzymes. Only weak relationships between accessory gland markers and catalase-like activity suggested a multi-glandular source of this enzyme. There was no relationship between the activity of any of the enzymes in the IVF patients with their fertilization rates in vitro or the establishment of pregnancy after IVF. Nor was there any correlation of enzyme activity with the morphology and percentage of motile spermatozoa in semen or with the percentage motility of spermatozoa immediately after swim-up or after overnight incubation. These findings suggest that the protective enzymes in the seminal plasma are contributed largely by the prostate and little by the epididymis, and that in most cases of IVF, they have no major influence on the outcome.      

Scanning Electron Microscopic Evaluation of Nonocclusive Excimer Laser-Assisted Anastomosis in Rabbits

Summary  Background. The nonocclusive Excimer laser-assisted bypass technique has been described in previous studies and proved to be a promising bypass operation in vascular brain surgery. Little is known about the morphological regeneration process of the laser-assisted anastomosis in time.  By way of a scanning electron microscopic study we examined the way in which the anastomosis site created by the nonocclusive Excimer laser-assisted anastomosis technique becomes endothelialized.  Methods. In 14 rabbits the internal jugular vein was placed in a loop on the abdominal aorta. The distal anastomosis was made using the nonocclusive Excimer laser-assisted technique. The proximal anastomosis was made either laser-assisted or conventional end-to-side. After clipping of the aorta between the two anastomoses sites the vein served as a bypass. To evaluate the endothelialization at the laser-assisted anastomosis site in time, a scanning electron microscopic study was performed.  Results. In the first hours after the bypass operation a new intimal surface is formed by fibrin and activated platelets. Some leukocytes are seen during the first days. The endothelialization process of the laser-assisted anastomosis site begins one day after the operation. The gradual endothelialization process evolved along two lines. First, endothelial cells grow from the side of the aorta to the bypass. Second, after one day solitary (blood-borne) endothelial cells deposit on the laser edge and the sutures, covering the platelet aggregates.  Conclusions. The endothelialization of the Excimer laser-assisted anastomosis is more or less completed 9 days after the operation. The edge created by the laser becomes smoother after a few days and is gone for the most part after 9 days.     

Monomeric site-specific nucleases for genome editing

Targeted manipulation of complex genomes often requires the introduction of a double-strand break at defined locations by site-specific DNA endonucleases. Here, we describe a monomeric nuclease domain derived from GIY-YIG homing endonucleases for genome-editing applications. Fusion of the GIY-YIG nuclease domain to three-member zinc-finger DNA binding domains generated chimeric GIY-zinc finger endonucleases (GIY-ZFEs). Significantly, the I-TevI-derived fusions (Tev-ZFEs) function in vitro as monomers to introduce a double-strand break, and discriminate in vitro and in bacterial and yeast assays against substrates lacking a preferred 5'-CNNNG-3' cleavage motif. The Tev-ZFEs function to induce recombination in a yeast-based assay with activity on par with a homodimeric Zif268 zinc-finger nuclease. We also fused the I-TevI nuclease domain to a catalytically inactive LADGLIDADG homing endonuclease (LHE) scaffold. The monomeric Tev-LHEs are active in vivo and similarly discriminate against substrates lacking the 5'-CNNNG-3' motif. The monomeric Tev-ZFEs and Tev-LHEs are distinct from the FokI-derived zinc-finger nuclease and TAL effector nuclease platforms as the GIY-YIG domain alleviates the requirement to design two nuclease fusions to target a given sequence, highlighting the diversity of nuclease domains with distinctive biochemical properties suitable for genome-editing applications.