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Biomedical subjects

M C Pietrogrande

Publications and source records attributed to M C Pietrogrande.

At least 19 recordsLinked to original sources

Progressive multifocal leukoencephalopathy in a child with hyperimmunoglobulin E recurrent infection syndrome and review of the literature.

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease due to infection with polyomavirus JC (JCV). PML occurs almost exclusively in immunocompromised patients, and although it has increased markedly in relation to AIDS, remains exceptional in children. We present the case of an immunocompromised child with hyperimmunoglobulin E recurrent infection syndrome (HIES) and pathologically-proven PML. HIES is a rare congenital immunodeficiency that to our knowledge has never before been reported in association with neurological complications. Following a recurrence of bronchopneumonia, the child's motor and cognitive functions deteriorated progressively in parallel with alterations on cerebral MRI. The neurological onset coincided with lymphocyte subset changes. PCR for JCV DNA did not detect the virus in CSF, and brain biopsy was required to secure the diagnosis. Antiviral treatment with cidofovir produced no benefit. Autopsy revealed the typical neuropathological findings of PML which were associated with inflammatory eosinophilic infiltrate (a marker of HIES). In accordance with the few pediatric PML cases reported and here reviewed, the child died five months after neurological onset.

Brain↗

[Cardiovascular abnormalities in Kawasaki disease. An Italian prospective study].

We report a prospective study performed over a 9 year period in 96 children with Kawasaki disease (mean age 35 +/- 29 months), 84 of whom < 5 years of age. The male/female ratio was 1.5 (57/39). A total of 38 patients had cardiac involvement, including flattened T waves in the ECG (10 patients), pericardial effusion (6 patients), myocarditis (1 patient), and coronary artery aneurysms (25 patients; frequency of aneurysms: 26%). All patients were evaluated during the acute phase (first month) of the illness. The first echocardiographic examination was performed 15 days (range 4.30 days) from the appearance of fever, and coronary aneurysms were observed in 23 patients; in 2 patients, however, aneurysms appeared later (2 and 6 months). Aneurysms were small (< or = 4.5 mm) in 12, medium (4.5-7 mm) in 11, and large (> 7 mm) in 12 patients. Male sex (p = 0.02), age < 12 months (p = 0.005), ESR (p = 0.001), platelet count (p = 0.009), and pericardial effusion (p = 0.02) were significantly related to the presence of aneurysm. Among females, incidence of aneurysms was significantly higher in infants < 12 months than in older patients (60 vs 6%, p < 0.001). Intravenous immunoglobulin treatment was started early (within 10 days) in 61 patients and late (> 10 days) in 22. Compared to late treatment, early i.v. immunoglobulin treatment was associated with smaller aneurysms and higher regression rate (67 vs 28%, p < 0.05). No difference was observed concerning frequency and number of dilated vessels as related to therapeutical regimens. Total i.v. immunoglobulin dose (2 g/kg) was administered over 1-2 days in 26 patients (scheme I) or over 4-5 days in 58 (scheme II). Frequency of aneurysms was significantly lower in patients treated early (p = 0.02). No myocardial infarctions or deaths occurred at short- or long-term follow-up.

Cardiovascular Diseases↗

Screening for delayed-hypersensitivity in Italian children: multicentric study by multitest skin testing.

The Multitest skin test allows the simultaneous intradermal application of seven standardized recall antigens in a reproducible manner. Response reading is based on a scoring system that distinguishes between normal and diminished delayed hypersensitivity (DH). To determine incidence and size of DH responses for each antigen in relation to age and sex in healthy Italian children, a multicentric study was performed on a representative paediatric population of 491 subjects (285 males and 296 females) aged from 4 months to 16 years. In both sexes DH reactivity as measured by score and number of positive responses increased significantly with age. The incidence of anergy was 8.8% for the whole population and decreased significantly with age in both sexes. Incidence of positive responses was highest for tetanus and diphteria toxoids, intermediate for Candida, Proteus and Streptococcus, and lowest for tuberculin and Trichophyton antigens. There was no significant difference between sexes in the incidence of positive response to each antigen.

Adolescent↗

Normal phase HPLC as a model system of specific benzodiazepine-receptor binding.

The hypothesis that benzodiazepines interact with their receptors in the CNS via hydrogen bonding mediated by the carbonyl and imine groups has been studied by correlating a physicochemical parameter affected by hydrogen bonds potentially accepted or donated by benzodiazepines with their binding constants to synaptosomal rat brain membranes. The reference physicochemical system chosen was normal phase high-performance liquid chromatography on mu-Bondapack NH2 (propylamine groups chemically bonded to porous silica) eluted with mixtures of n-hexane and 2-propanol. A strong correlation has been found for binding of the implicated groups to the column and to the receptor.

1-Propanol↗

Study of the lipophilic character of a series of beta-carbolines.

The lipophilic character of a series of beta-carbolines has been studied. The RM values were measured by means of a reversed-phase thin-layer chromatographic (TLC) technique and compared with the RM values obtained by high-performance TLC (HPTLC), the log k' obtained by high-performance liquid chromatography (HPLC), and the log P values. The best equation shows a very good linear relationship between our RM values and the classical log P values obtained using an octanol-water system. The choice of a pH of 13.0 for the TLC system allowed the measurement of the RM values of molecules in their non-ionized form. The deviations from the linear relationship shown by the RM(HPTLC) and log k' values of two compounds were due to the fact that both compounds were at least partially ionized at the pH of 7.0 at which the HPTLC and HPLC determinations were carried out.

Carbolines↗

Defective in vitro production of gamma-interferon and tumor necrosis factor-alpha by circulating T cells from patients with the hyper-immunoglobulin E syndrome.

Circulating T cells from four patients with the hyper-IgE syndrome were found to produce significantly lower concentrations of interferon-gamma (IFN-gamma) in response to stimulation with phytohemagglutinin (PHA) than did T cells from eight age-matched healthy controls, three patients with atopic dermatitis and one patient with chronic granulomatous disease. A clonal analysis revealed that patients with hyper-IgE syndrome had markedly lower proportions of circulating T cells able to produce IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) in comparison with controls. In contrast, the proportions of peripheral blood T cells able to produce IL-4 or IL-2 were not significantly different in patients and controls. All the four patients with hyper-IgE syndrome showed high proportions of circulating CD4+ helper T cells able to induce IgE synthesis in allogeneic B cells, as well. Such an activity for IgE synthesis appeared to be positively correlated with IL-4 production by T cells and inversely related to the ability of the same T cells to produce IFN-gamma. Since IFN-gamma exerts an inhibitory effect on the synthesis of IgE and both IFN-gamma and TNF-alpha play an important role in inflammatory reactions, we suggest that the defective production of IFN-gamma may be responsible for hyperproduction of IgE and the combined defect of IFN-gamma and TNF-alpha may contribute to the undue susceptibility to infections seen in patients with hyper-IgE syndrome.

Adolescent↗

The influence of lipophilic character on receptor binding affinity of a series of beta-carbolines.

A quantitative study of the relationship between structure and receptor binding affinity of a series of 16 beta-carbolines showed the influence of lipophilic character and hydrogen bonding capability of substituents in position 3. Some data taken from the literature enabled us to add some evidence about the influence of planarity of ring C and bulky substituents in position 1 in determining the receptor binding affinity.

Animals↗

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.

Adolescent↗

Pharmacokinetics of ketoconazole and treatment evaluation in candidal infections.

Twenty six children with candidiasis, aged between 5 months and 14 years, were treated with different formulations and regimens of ketoconazole. Fifteen children had alimentary tract candidiasis, two had oesophagitis, one had urinary tract candidiasis, two vaginitis, two septicaemia, one endo-ophthalmitis, and three had chronic pulmonary illness with persistence of Candida albicans in sputum. Daily drug doses ranged from 3 to 13 mg/kg and duration of treatment from seven days to 18 months. Pharmacokinetic studies in 22 of the children are reported. A total of 3 mg/kg/day given in three divided doses did not yield sufficiently high concentrations, which were achieved with a daily dose of 8 to 10 mg/kg. The effectiveness of treatment was proved by negative mycological tests (cultures or specific antibodies, or both) in 88%, by cure in 73%, and improvement in 11%. In three patients evaluation was not possible due to an insufficiently proved diagnosis. Nausea and pyrosis in four patients were the only side effects noted and no laboratory abnormalities were found. To achieve therapeutic concentrations of ketoconazole in children we suggest a daily dosage of 7 to 10 mg/kg in two or three divided doses.

Adolescent↗

Immune status in children with acute lymphocytic leukemia. Observations in 67 cases.

67 children affected with acute lympocytic leukemia were immunologically evaluated for lymphocytic markers, serum immunoglobulins and delayed hypersensitivity skin tests at the onset, in remission and after cessation of therapy. E, EA rosettes and surface Ig assayed significantly lower in leukemic children than in matched controls, except for three cases of T-cell leukemia in which E rosettes were very high. After cessation of therapy almost normal results were obtained. As for serum Ig, the only abnormal finding was that of low IgM during therapy. The skin tests with Varidase, Candidine, Mumps antigen and DNCB were not significantly different at onset and in remission. As for DNCB test, the negative responses at onset often became positive in remission, but only when the test was performed before any treatment (anamnestic-like response?). One of the three patients with T-cell leukemia relapsed after 8 months: strangely enough, no surface marker could be detected on that occasion. We could not find any relationship between various immunological tests, or between these tests and prognosis; chemotherapy proved active in suppressing cellular immunity, especially the primary cellular response.

Adolescent↗