[Central nervous system in IgG4-related disease: case report and literature review]. / Afeccion del sistema nervioso central en la enfermedad relacionada con IgG4: descripcion de un caso y revision de la bibliografia.

INTRODUCTION: IgG4-related disease is a recently described multisystemic clinical entity that can occur with different clinical manifestations. The most often affected organs are the pancreas, bile duct and salivary glands, with unusual central nervous system affection. CASE REPORT: A 33 year old woman who presented with cognitive impairment, hallucinations, headache, convulsive syndrome, maxillary sinus inflammation with bone involvement and evidence of pachymeningitis and panhypopytuirarism with meningeal biopsy that confirmed IgG4-related disease, after ruling out secondary causes. Treatment was started with steroids and azathioprine without relapses after 12 months follow-up. CONCLUSIONS: IgG4-related disease should be considered in cases of hypertrophic pachymeningitis and hypophysitis especially when no other cause has been found, even if they are not accompanied by other systemic disease manifestations, having ruled out other common causes. The treatment of choice is glucocorticoids and it could be needed to add another immuno-suppressant agent as steroid sparing and to prevent relapses. Prospective studies are needed to evaluate the different clinical and paraclinical manifestations and to establish the results of long-term treatment.

TITLE: Afeccion del sistema nervioso central en la enfermedad relacionada con IgG4: descripcion de un caso y revision de la bibliografia.Introduccion. La enfermedad relacionada con IgG4 es una entidad clinica multisistemica recientemente descrita y que se presenta con diferentes manifestaciones clinicas. Los organos que estan afectados con mayor frecuencia son el pancreas, la via biliar y las glandulas salivales, y es menos frecuente la afeccion del sistema nervioso central. Caso clinico. Mujer de 33 años con alteraciones cognitivas, alucinaciones, cefalea, sindrome convulsivo, sinusitis maxilar con afeccion osea y evidencia de paquimeningitis y panhipopituitarismo, con biopsia meningea que confirmo una enfermedad relacionada con IgG4, tras haberse descartado causas secundarias. Se inicio tratamiento con glucocorticoides y azatioprina, sin recaidas despues de 12 meses de seguimiento. Conclusiones. Se debe considerar el diagnostico de enfermedad relacionada con IgG4 en casos de paquimeningitis hipertrofica e hipofisitis, incluso sin que se acompañen de otras manifestaciones sistemicas, siempre que se hayan descartado otras causas mas frecuentes. El tratamiento de eleccion son los glucocorticoides, y puede ser necesario añadir otro inmunosupresor como ahorrador de esteroides y para evitar las recaidas. Se necesitan estudios prospectivos para evaluar las diferentes manifestaciones clinicas y paraclinicas y establecer los resultados del tratamiento a largo plazo.

A novel mutation in the connexin 46 gene (GJA3) causes autosomal dominant zonular pulverulent cataract in a Hispanic family.

PURPOSE: A five-generation Hispanic pedigree with autosomal dominant zonular pulverulent cataract was studied to identify the causative mutation in connexin 46 (Cx46), a gap junction protein responsible for maintaining lens homeostasis. METHODS: Twenty-six individuals from the family were comprehensively clinically examined. DNA was extracted from their peripheral blood samples. The DNA was used for automated genotyping with fluorescently labeled microsatellite markers and for mutation detection by automated sequencing. RESULTS: A novel D3Y missense mutation in GJA3 segregated with autosomal dominant (AD) zonular pulverulent cataract throughout the family. The mutation was absent in the unaffected individuals in the family and in 230 control chromosomes. CONCLUSIONS: A novel mutation causing AD zonular pulverulent cataract has been identified in a Hispanic Central American family. This is the first report of a mutation in GJA3 causing autosomal dominant congenital cataract (ADCC) in this ethnic group. It is also the first reported cataract-causing mutation in the NH2-terminal region of the Cx46 protein.

Disseminated histoplasmosis in children: the role of itraconazole therapy.

OBJECTIVES: To describe the clinical characteristics and laboratory diagnosis of seven children with disseminated histoplasmosis and evaluate the effectiveness of itraconazole therapy in this severe form of the mycosis as well as to determine the long term results of such treatment. METHODS: The diagnosis of histoplasmosis was based on the direct observation of Histoplasma capsulatum var. capsulatum and/or on the isolation of the fungus from pathologic materials; the results of the serologic tests were taken into consideration. Chest roentgenograms also contributed to the diagnosis. PATIENTS: The patients were seven rural children, five girls and two boys, ages 1 to 14 years (mean, 4.6), with a confirmed diagnosis of disseminated histoplasmosis and who had no underlying disease other than malnourishment. RESULTS: The seven children experienced a subacute febrile syndrome for 4 months accompanied by anorexia, weight loss and signs of reticuloendothelial involvement such as lymph node hypertrophy, hepatomegaly and/or splenomegaly. The lung revealed roentgenographic alterations consisting mainly of nodular infiltrates. All patients received itraconazole orally in a mean dosage of 7.2 mg/kg/day, for variable periods (3 to 12 months), depending on the individual response and the toxic effects of the medication. One of the patients who was improving after 1 month of treatment was taken from the hospital by his guardian against medical advice and died shortly afterward. The remaining six patients responded to the treatment with marked clinical improvement and showed negative cultures and decreases in anti-H. capsulatum antibody titers after 3 months of treatment. Only one patient, the youngest and most severely affected child, exhibited hepatotoxicity, which subsided when itraconazole was discontinued. Extended follow-up studies revealed no relapses. CONCLUSION: The results of this study indicate that itraconazole is effective for treatment of disseminated childhood histoplasmosis. More studies should be performed to determine the most appropriate dosage and the optimal duration of itraconazole treatment in children.

Single daily dose amikacin in paediatric patients with severe gram-negative infections.

Twenty-five children with serious Gram-negative infections were treated in a prospective study with amikacin 20 mg/kg administered in a single daily dose as a 30 min iv infusion for 4 to 12 days. In nine cases the amikacin was combined with beta-lactam antibiotics. Escherichia coli were the most frequent bacteria isolated followed by K. pneumoniae, Providencia and Enterobacter spp. and Pseudomonas aeruginosa with MICs ranging from 1 to 16 mg/l. Mean (+/- S.D.) peak and trough concentrations of days 1 and 4 of therapy ranged from 49 +/- 13.5 to 53.6 +/- 13.4 mg/l and 6 + 1.4 to 7.7 +/- 4.1 mg/l respectively. All patients were clinically and bacteriologically cured. No significant adverse reactions were observed. The results suggest that administration of a single daily dose of 20 mg/kg amikacin should be considered practical and safe in children. Further studies are needed.