Preliminary evaluation of vitiligo using in vivo reflectance confocal microscopy

BACKGROUND: Vitiligo is the most common pigmentary disorder with a global incidence from 0.1% to 2% in different geographical areas. Histopathology and histochemistry have shown the reduction of melanocytes in achromic patches, but microscopic changes of lesional and non-lesional skin are still not completely understood. Reflectance confocal microscopy (RCM), based on the different light reflectance index of cutaneous structures, allowed in vivo, en face microscopic evaluation of superficial skin layers with a resolution similar to skin histology. AIM: The purpose of this study was to evaluate RCM features of lesional and non-lesional skin of vitiligo patients. Moreover, re-pigmented areas were taken into consideration in order to evaluate melanocyte response to ultraviolet B (UVB) radiation. SUBJECTS AND METHODS: Sixteen patients of different phototypes affected by active non-segmental vitiligo and 10 controls were enrolled in the study. In vivo skin imaging was done using a commercially available RCM (Lucid, Vivascope 1500. Re-pigmented areas from 6 to 16 patients (after UVB narrow-band therapy) were also examined. RESULTS: Vitiligo lesions showed the disappearance of the bright rings normally seen at the dermo-epidermal junction. Moreover, non-lesional skin of vitiligo patients showed unexpected changes as the presence of half-rings or scalloped border-like features of the bright papillary rings. In re-pigmented areas after UVB narrow band therapy, the presence of activated, dendritic melanocytes was seen. CONCLUSIONS: Considering our results, and following further studies, RCM clinical applications could be used in the therapeutic monitoring and evaluation of the evolution of vitiligo.     

Immunohistological study of grumose degeneration of the dentate nucleus in progressive supranuclear palsy

The grumose degeneration observed in the dentate nuclei of 7 cases of progressive supranuclear palsy (PSP) was studied with a panel of antibodies which included 2 neurofilaments, Tau and ubiquitin. Dentate nucleus neurons were negative with all antibodies except ubiquitin which showed a slightly positive homogeneous pattern of staining. The amorphous material surrounding swollen or normal neurons was strongly positive for neurofilament and subunits and numerous torpedoes were observed in the granular layer of the cerebellar cortex. Our results confirm that grumose degeneration consists in degeneration of terminal axons of Purkinje cells in the dentate nucleus. The positivity of dentate nucleus neurons for ubiquitin may support the concept of synaptic dysfunction between Purkinje cells and dentate nucleus neurons.     

AC/A ratios in myopic and emmetropic Hong Kong children and the effect of timolol§

Purpose: Caucasian children with myopia have elevated response accommodative vergence to accommodation (AC/A) ratios. The purpose of this study was twofold: to determine if response AC/A ratios vary with refractive error and with myopic progression rate in Hong Kong Chinese children, and to determine the effect of beta‐adrenergic antagonism with topical timolol application on AC/A ratios. Methods: Thirty children aged eight to 12 years participated in the study. All refractive errors were corrected with spectacle lenses. Accommodative responses were measured using a Shin‐Nippon autorefractor and concurrent changes in vergence were assessed using a vertical prism and a Howell‐Dwyer card at three metres and 0.33 metre. Accommodative demand was altered using plus or minus two dioptre lenses and lens‐ and distance‐induced response AC/A ratios were calculated. Measurements were repeated 30 minutes after the instillation of topical timolol maleate (0.5 per cent). Results: AC/A ratios appeared higher in progressing myopic children but the difference was not statistically significant. Timolol application reduced accommodative convergence (AC) in the stable myopes (reduction = ‐3 ± 1.14^A) but not in the emmetropes (0.69 ± 0.9^P) or progressing myopes (0.16 ± 0.43^A) and this difference between refractive groups was statistically s ignificant (F^2,27= 3.766; P= 0.036). However, timolol did not produce a significant change in the accommodative response to positive or negative lenses or response AC/A ratios. Conclusions: We did not find that AC/A ratios in myopic Chinese children were elevated and therefore, it is unlikely that elevated AC/A ratios are responsible for the high levels of myopia that occur in Hong Kong. The finding that timolol reduced AC in the stable myopes suggests that the autonomic control of accommodative convergence in these children may be different from that in emmetropic children and those with progressing myopia.     

Activation of guinea pig eosinophil respiratory burst by leukotriene B4: role of protein kinase C

Leukotriene B4 (LTB4) and the protein kinase C activator, 4-beta-phorbol dibutyrate (PDBu), both induced a pronounced and concentration-dependent stimulation of hydrogen peroxide (H2O2) generation by purified guinea pig peritoneal eosinophils in the concentration range 1 nM-1 microM. The LTB4 response was inhibited competitively by the specific LTB4 receptor antagonist, U-75302, with a KB of 25 nM, while the concentration-response curves for both stimuli were shifted rightwards (3.8-fold and 2.8-fold for LTB4 and PDBu, respectively) by the competitive protein kinase C inhibitor, 1-O-hexadecyl-2-O-methylglycerol at a concentration of 300 microM. LTB4 appears, therefore, to induce respiratory burst in eosinophils via a receptor-mediated mechanism involving protein kinase C.     

Bidirectional cavopulmonary shunts: clinical applications as staged or definitive palliation

A standard Glenn anastomosis between the superior vena cava and the right pulmonary artery has been the accepted mode of treatment for patients with complex cyanotic congenital heart disease. We report our experience in 18 patients with such disease who underwent a bidirectional cavopulmonary shunt because of increasing cyanosis and growth cessation. All patients were considered less than "ideal" candidates for a Fontan procedure. We divided the patients into two groups: group 1 had azygos continuation and group 2 did not. Fourteen patients required hypothermic cardiopulmonary bypass. Bidirectional pulmonary blood flow was achieved in all patients. Only 1 death occurred (group 2). The improvement in oxygen saturation and overall clinical condition of these patients, together with the low mortality and morbidity, is encouraging. However, long-term follow-up is mandatory for a comprehensive evaluation of this surgical approach as definitive palliation or as a first stage for a Fontan operation.     

Characterization of the procoagulant chain derived from human high molecular weight kininogen (Fitzgerald factor) by human tissue kallikrein

Human high molecular weight kininogen (HMWK), a single-chain protein with mol wt 120,000, is cleaved by human urinary kallikrein (HUK) to release kinin from within a disulfide loop and form a two-chain protein that retains all the procoagulant activity of the native molecule. Cleavage of HMWK by HUK is associated with a reduction in size to mol wt 115,000, as assessed by SDS-PAGE of unreduced protein, whereas the two chains of the reduced protein present together as a single broad band with mol wt 64,000. The 64,000 chain with procoagulant activity was chromatographically separated from the nonfunctional chain of similar size. The homogeneous procoagulant chain had an amino acid composition similar to that of smaller procoagulant ("light") chains isolated by others upon cleavage of HMWK with plasma kallikrein and elicited an antiserum that was monospecific by Ouchterlony analysis and inhibited the procoagulant function of HMWK. Thus, the limited proteolysis of HMWK by HUK has permitted, for the first time, the isolation of a stable procoagulant chain that is equal in size to the nonfunctional chain. The common terminology of "heavy" and "light" chain for kinin-free kininogen obtained with plasma kallikrein reflects the continued degradation of the procoagulant carboxyterminal chain and is not appropriate for the initial two-chain product formed when kinin is released from HMWK. It is proposed that the initial cleavage products of HMWK be designated the A-chain, the B-fragment, and the C- chain, representing the amino-terminal chain, the released vasoactive peptide containing the bradykinin sequence, and the carboxy-terminal procoagulant chain, respectively. Thus, intact HMWK would contain, in sequence, A, B, and C regions.     

Metabolic abnormalities associated with initiation of systemic treatment for psoriasis: evidence from the Italian Psocare Registry

Objective To evaluate variations in laboratory parameters and diagnoses of selected clinical conditions up to 16 weeks after starting a new systemic psoriasis treatment for Psocare Registry enrollees. Design Prospective cohort study. Setting Italian public referral centres for psoriasis treatment. Patients First‐time recipients (n = 10,539) of continuous systemic psoriasis treatment for at least 16 weeks. Main outcome measure Mean variations in (weeks 8 and 16) and proportions of patients reaching a clinically meaningful increase in serum levels (week 16) of total and low‐density lipoprotein cholesterol, triglycerides, aspartate amino transferase, alanine amino transferase and creatinine, as well as week‐16 cumulative incidences of new diagnoses of diabetes mellitus and arterial hypertension. Results Mean cholesterol and triglyceride levels significantly increased in patients treated with acitretin or cyclosporine. Mean triglyceride levels also increased in efalizumab‐ and etanercept‐treated patients. Mean transaminase values increased in methotrexate‐treated patients, and mean aspartate amino transferase levels increased in infliximab‐treated patients. The average serum creatinine value increased in cyclosporine‐treated patients. Acitretin and cyclosporine were associated with risk of hypercholesterolaemia (odds ratios 1.51 and 1.34) and acitretin with risk of hypertriglyceridaemia (odds ratio 1.43). Methotrexate and infliximab were associated with risk of more than doubling the upper normal aspartate amino transferase (odds ratios 2.06 and 1.87) and alanine amino transferase (odds ratios 2.38 and 1.74) values. The relative risk of developing arterial hypertension and diabetes was increased for patients receiving cyclosporine (odds ratios 3.31 and 2.88). Conclusion Systemic treatments for psoriasis resulted in heterogeneous effects on the parameters analysed.