Home infusion program with enzyme replacement therapy for Fabry disease: The experience of a large Italian collaborative group.

Fabry disease (FD) [OMIM 301500] is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme alpha-galactosidase A, resulting in progressive multisystem accumulation of globotriaosylceramide (Gb3). Although the introduction of Enzyme Replacement Therapy (ERT) resulted in a variety of clinical benefits, life-long intravenous (IV) treatment with ERT with an every other week schedule, may interfere with daily life activities and impact on QoL. We report here a multicentric, observational, longitudinal data analysis on a large cohort of 85 Italian FD patients (45 males, 40 females) from 11 out of 20 Italian regions, who received a cumulative number of 4269 home infusions of agalsidase alfa. For the whole cohort, the average duration of home therapy was 1 year and 11 months (range 3 months-4 years and 6 months), and during this period, compliance to treatment (number of infusions performed vs scheduled) reached 100%. The EQ-5 VAS scale was administered to patients to evaluate the self-reported QoL, 58% of patients showing an increase of EQ-5 VAS score at follow up compared to baseline (home treatment start) or remaining stable. A mild increase of average disease severity, measured through Mainz Severity Score Index (MSSI), was found during hospital treatment (p < 0,007), while it remained stable between the first home therapy infusion and last follow up. Interestingly, 4 out of 7 (57%) patients, showing an improvement in FD-related clinical status after starting home therapy, had previously a sub-optimal compliance to treatment during the period of hospital treatment management. Only 4 adverse non serious reactions (0,093%) were reported totally in 2 patients during home treatment. We conclude that home infusions in eligible patients with FD are safe, contribute to improve treatment compliance and therapeutic clinical outcomes, and may have a positive impact on self-perceived QoL.

Intrafamilial phenotypic variability in four families with Anderson-Fabry disease.

We analysed the clinical history of 16 hemizygous males affected by Anderson-Fabry Disease, from four families, to verify their intrafamilial phenotypic variability. Seven male patients, ranging from 26 to 61 years of age, died, whereas nine (age range 23-55) are alive. Eleven patients have undergone enzyme replacement therapy (ERT) for a period of 5-10 years. We have found a wide range of intrafamilial phenotypic variability in these families, both in terms of target-organs and severity of the disease. Overall, our findings confirm previous data from the literature showing a high degree of intrafamilial phenotypic variability in patients carrying the same mutation. Furthermore, our results underscore the difficulty in giving accurate prognostic information to patients during genetic counselling, both in terms of rate of disease progression and involvement of different organs, when such prognosis is solely based on the patient's family history.

Inflammatory pseudotumour of the liver: a case report.

A case of inflammatory pseudotumour of the liver is reported. Together with a brief review of inflammatory pseudotumours we also present the clinical picture and pathologic findings of this very rare tumour-like condition with only 31 cases quoted in the medical literature. We also discuss the difficulty of making a correct diagnosis of the condition.

Membrane-associated binding sites for indoleacetic acid in the rice coleoptile.

As described previously, the sensitivity of rice (Oryza sativa L.) coleoptiles to auxin is modulated by oxygen. Under anoxia, coleoptile elongation is insensitive to exogenously applied indole-3-acetic acid (IAA), whereas its sensitivity increases in air in the presence of the exogenous stimulus. Here we report the presence of two independent classes of membrane-bound IAA-binding sites in air-grown coleoptiles. Their binding activity is strictly correlated with the system's sensitivity to IAA. We designate them as site A (high affinity) and site B (low affinity). Site A shows a relatively fast response to anoxia, and is highly specific for auxins. Regulation of site-A binding activity through ATP, whose availability decreases under anoxia, is postulated. A role as auxin carrier is suggested for site B.

DNA methylation of embryogenic carrot cell cultures and its variations as caused by mutation, differentiation, hormones and hypomethylating drugs.

The level of auxin - both natural and synthetic - in the medium has a strong effect on the level of 5-methyl-cytosine in the DNA of carrot cells in culture. This level may vary from approximately 15% to 70% of total cytosine without apparent effects on growth rate and cell morphology. No effect was seen with cytokinin. During somatic embryogenesis, in the absence of hormones, variations were seen in the level of methylation according to a characteristic pattern. If hypomethylation is induced with drugs such as azacytidine, ethionine or ethoxy-carbonyl-pyrimidine, embryogenesis is immediately blocked. A mutant was isolated which is resistant to the action of hypomethylating drugs. It shows variations in the methylation pattern and variations in indole-acetic acid metabolism. In addition its regeneration is often associated with the production of tumors.

Counterimmunoelectrophoresis and latex particle agglutination in the etiologic diagnosis of presumed bacterial pneumonia in pediatric patients.

A commercial latex agglutination (LA) kit (Wellcogen, Wellcome Diagnostics) used to detect bacterial polysaccharide antigens (Haemophilus influenzae type b and Streptococcus pneumoniae) was compared with a modified counterimmunoelectrophoresis technique and blood culture for etiologic diagnosis of presumptive bacterial pneumonia requiring hospitalization in 60 infants and children. Serum, urine and either sputum or nasopharyngeal secretions were collected during the first 5 days of therapy for antigen detection. Blood culture was positive in 6 of 52 (11.5%) of cases. Antigens were detected by counterimmunoelectrophoresis and/or LA in 13 of 60 (21.7%) serum samples, 2 of 16 (12.5%) unconcentrated urine samples, 19 of 42 (45.2%) urine samples concentrated 25-fold and 21 of 45 (46.7%) sputum or nasopharyngeal secretions. Antibiotic treatment for 5 days did not affect the antigen detection rate. Counter-immunoelectrophoresis was more sensitive than LA in serum and urine but not in sputum. However, because false positive reactions were frequently obtained with LA on nasopharyngeal secretions of an age-matched control group, this test appears unreliable.

Free and bound indole-acetic acid is low in the endosperm of the maize mutantdefective endosperm-B18.

The maize mutant defective endosperm-B18 (de (*)-B18), which is recessive to its wildtype, accumulates substantially less dry matter in the endosperm than its normal counterpart. Both free and bound indole-acetic acid (IAA) content has been measured at 5 different developmental stages. In endosperm tissue, the level of IAA is at least 15 times lower in the mutantde (*) -B18 than in the wildtype. The situation found in the diploid tissues is somewhat different: in the mature embryo the level of total IAA is lower in the mutant than in the wildtype, while in 4-day old seedlings the level of total IAA is, to some degree, similar in both genotypes. Naphthalene-acetic acid (NAA), a stable synthetic auxin which mimics IAA in its biochemical effects, is able to normalize the seed weight of the mutant when applied to developing grains. The results favor the conclusion that in maize endosperm the mutationde (*) -B18 is involved in IAA metabolism.

[Immunohistological aspects of nephropathy with minimal lesions]. / Aspetti immunoistologici della nefropatia a lesioni minime.

Renal biopsies from 32 patients, whose light microscopy showed a pattern of minimal changes nephropathy, have been submitted to immunohistological examination. On the basis of immunofluorescence pattern we separated the cases into three groups: the first group (12 cases) was characterized by absence of any glomerular deposit. The second group (9 cases) showed focal and segmental deposits of IgM and sometimes C3 on capillary walls. In the third group (11 cases) we observed slight deposits of IgM and sometimes C3 "comma like" over glomerular structures in all glomeruli. The site of these last deposits was sometimes mesangium and sometimes the capillary walls. The results of immunohistological examinations gave no information about the pathogenetic mechanisms of minimal changes nephropathy. We observed that the patients enclosed in the second group had a worse clinical prognosis, compared with the other two groups.