Extracorporeal photochemotherapy for paediatric patients with graft-versus-host disease after haematopoietic stem cell transplantation

This study aimed to ascertain whether extracorporeal photochemotherapy (ECP) is an effective treatment for paediatric patients with refractory graft-versus-host disease (GVHD). From January 1992 to December 2000, 77 children (median age 8.6 years) with either acute (n = 33) or chronic (n = 44) GVHD, resistant to conventional immunosuppressive therapy, were treated with ECP in four Italian paediatric hospitals. After ECP, acute GVHD involving skin, liver and gut responded completely in 76%, 60% and 75% of patients respectively. The 5-year overall survival was 69% for responding patients vs 12% for non-responders (P = 0.001). Among the 44 children with chronic GVHD, 15 (44%) showed a complete response and 10 (29%) a significant improvement after ECP. The 5-year overall survival was 96% for responders vs 58% for non-responders (P = 0.04). Our results suggest that ECP is an effective treatment that may be useful in paediatric patients with either acute or chronic GVHD who have failed to respond to standard immunosuppressive therapy.     

Postsynaptic modulation of AMPA- and NMDA-receptor currents by Group III metabotropic glutamate receptors in rat nucleus accumbens

Whole cell patch clamp recordings from rat nucleus accumbens neurons were made in order to study the effect of metabotropic glutamate receptors and dopamine on postsynaptic glutamate receptor mediated currents. AMPA- and NMDA-R currents were evoked by flash photolysis of caged glutamate, while spike-dependent release of neurotransmitters was prevented by adding tetrodotoxin and bicuculline to the bath solution. Spontaneous potentiation of NMDA- but not AMPA-R current was observed in the early phase of stimulation, followed by depotentiation and subsequent stabilization. The Group III metabotropic glutamate receptor antagonist MAP4 induced a transient potentiation of both AMPA- and NMDA-R current amplitudes, without affecting rise times and decay time constants. In contrast, the Group I-II metabotropic glutamate receptor antagonist MCPG and the neurotransmitter dopamine did not exert significant effects on either AMPA- or NMDA-R currents. These data suggest that at least one of the Group III subtypes is located postsynaptically in the nucleus accumbens and is able to dampen the activity of ionotropic glutamatergic receptors. In contrast, our results do not support a modulation of postsynaptic AMPA- and NMDA-R currents by Group I/II metabotropic glutamate receptors or dopamine. Modulation of both AMPA- and NMDA-R currents in the nucleus accumbens is likely to play a major role in setting the cellular excitability in response to behaviourally relevant limbic inputs, and in regulating the plasticity of these responses.     

Gap junctions in the inner ear: comparison of distribution patterns in different vertebrates and assessement of connexin composition in mammals

The distribution and size of gap junctions (GJ) in the sensory epithelia of the inner ear have been examined in a reptile (gecko), birds (chicken and owl), and mammals (mouse, guinea pig, gerbil, and bat), and the connexin composition of GJs in the mammalian inner ear has been assessed. Freeze fracture revealed a common pattern of GJ distribution in auditory and vestibular sensory epithelia in the different vertebrate classes. In all these tissues, GJs are numerous, often occupying more than 25% of the plasma membrane area of supporting cells and sometimes composed of more than 100,000 channels. Screening for 12 members of the connexin family in the mammalian inner ear by RT-PCR, Western blotting, and immunohistochemistry revealed four connexin isotypes, cx26, cx30, cx31, and cx43, in the cochlea and three, cx26, cx30, and cx43, in the vestibular organs. With antibodies characterised for their specificity, cx26 and cx30 colocalised in supporting cells of the organ of Corti, in the basal cell region of the stria vascularis, and in type 1 fibrocytes of the spiral ligament. No other connexin was detected in these regions. Cx31 was localised among type 2 fibrocytes below the spiral prominence, a region where cx30 was not expressed and cx26 expression appeared to be low. Cx43 was detected only in the region of "tension fibrocytes" lining the inner aspect of the otic capsule. This suggests separate functional compartments in the cochlea. In addition to cx26 and cx30, cx43 was detected in supporting cells of the vestibular sensory epithelia. Where cx26 and cx30 were colocalised, double immunogold labelling of thin sections showed both cx26 and cx30 evenly distributed in individual GJ plaques, a pattern consistent with the presence of heteromeric connexons. Coimmunoprecipitation of cochlear membrane proteins solubilised with a procedure that preserves the oligomeric structure of connexons confirmed the presence of heteromeric cx26/cx30 connexons. Heteromeric cx26/cx30 connexons may be unique to the inner ear, which could be one factor underlying the non-syndromic character of the deafness caused by mutations in cx26.     

The health gap in Mexico,measured through child mortality

OBJECTIVE: To estimate the health gap in Mexico, as evidenced by the difference between the observed 1998 mortality rate and the estimated rate and the estimated rate for the same year according to social and economic indicators, with rates from other countries. MATERIAL AND METHODS: An econometric model was developed, using the 1998 child mortality rate (CMR) as the dependent variable, and macro-social and economic indicators as independent variables. The model included 70 countries for which complete data were available. RESULTS: The proposed model explained over 90% of the variability in CMR among countries. The expected CMR for Mexico was 22% lower that the observed rate, which represented nearly 20,000 excess deaths. CONCLUSIONS: After adjusting for differences in productivity, distribution of wealth, and investment in human capital, the excess child mortality rate suggested efficiency problems in the Mexican health system, at least in relation to services intended to reduce child mortality. The English version of this paper is available at: http://www.insp.mx/salud/index.html.     

Papular xanthoma associated with angiokeratoma of Fordyce: considerations on the nosography of this rare non-Langerhans cell histiocytoxanthomatosis

BACKGROUND: Papular xanthoma (PX) is a rare normolipidemic non-Langerhans cell histiocytoxanthomatosis affecting both children and adults. OBJECTIVE: We describe an adult case of PX associated with angiokeratoma of Fordyce and review the literature in order to compare and discuss previous reports. METHODS: We studied the clinical, histopathological, immunocytochemical and ultrastructural findings. RESULTS: We report the findings of our case and compare our case with those described in the literature. CONCLUSIONS: Three clinical patterns of PX appeared to emerge in the review of the literature: a self-healing form, a persistent form and a progressive form. The progressive form of PX can be considered the same clinical entity that is also described as progressive nodular histiocytosis.     

Intravascular hemolysis in patients with new-generation prosthetic heart valves: a prospective study

OBJECTIVE: A prospective clinical study was designed to assess the frequency and severity of intravascular hemolysis in patients with new-generation, normally functioning prosthetic heart valves. METHODS: Hemolysis was evaluated in 172 patients with a mechanical prosthesis (53 CarboMedics and 119 Sorin Bicarbon) and in 106 patients with a bioprosthesis (15 St Jude Medical Toronto, 19 Baxter Perimount, and 72 Medtronic Mosaic) in the aortic position, mitral position, or both. Aortic valve replacement was performed in 206 patients, mitral valve replacement in 59 patients, and double valve replacement in 13 patients. The presence of hemolysis was assessed on the basis of the level of serum lactic dehydrogenase and serum haptoglobin and the presence and amount of reticulocytes and schistocytes in the peripheral blood. Severity of intravascular hemolysis was estimated on the basis of serum lactic dehydrogenase. Clinical, echocardiographic, and hematologic evaluations were performed 1, 6, and 12 months after discharge. RESULTS: None of the 278 patients experienced decompensated anemia, whereas at 12 months, mild subclinical hemolysis was identified in 49 patients, 44 (26%) with a mechanical prosthesis and 5 (5%) with a bioprosthesis (P <.001). At multivariate analysis, independent predictors of the presence of subclinical hemolysis were mitral valve replacement (P <.001), use of a mechanical prosthesis (P =.002), and double valve replacement (P =.02). Frequency of hemolysis in patients with stented aortic bioprostheses was 3%, whereas it was absent in those with stentless valves. Among mechanical valve recipients, double versus single valve replacement (P =.04) and mitral versus aortic valve replacement (P =.05) were correlated with the presence of hemolysis; double valve recipients also showed a more severe degree of hemolysis (P =.03). In patients with a Sorin Bicarbon prosthesis, hemolysis was less frequent (22% vs 34%, P =.09) and severe (P <.001) than in those with a CarboMedics prosthesis. CONCLUSIONS: In normally functioning prosthetic heart valves, subclinical hemolysis is a frequent finding. A low incidence of hemolysis is found in stented biologic prostheses, and it is absent in stentless aortic valves. Modifications of valve design may contribute to minimize the occurrence of hemolysis in mechanical prostheses.