Consensus Conference on Nasal Polyposis.
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Administration, Intranasal↗
Biomedical subjects
J Onorato
Publications and source records attributed to J Onorato.
Evaluation of triterpene glycoside estrogenic activity using LC/MS and immunoaffinity extraction.
We present a study on the mass spectral as well as the binding properties of three triterpene glycosides (cimicifugoside, cimiracemoside F, 27-deoxyactein) contained in black cohosh to the ligand binding domain of estrogen receptor beta (ER-beta). Using affinity ultrafiltration and LC/ MS detection, initial experiments using estradiol and the phytoestrogens daidzein and genistein (compounds known to bind ER-beta) were performed to serve as positive controls. The same affinity techniques and LC/MS procedures were then employed to show that neither the triterpene glycosides nor their enzymatically prepared aglycons bound significantly to ER-beta, except for 27-deoxyactein aglycon, which showed weak binding affinity (4%). Additionally, metabolites of the aglycons were prepared by incubation with female human liver microsomes and subjected to binding experiments with ER-beta. No significant binding of the metabolites to the receptor was observed. Further studies are needed to fully characterize whether these triterpene glycosides as well as other components of black cohosh in this plant extract bind to the estrogen receptor alpha (ER-alpha).
Chemistry Techniques, Analytical↗
Transcranial magnetic stimulation identifies upper motor neuron involvement in motor neuron disease.
OBJECTIVE: To evaluate the sensitivity of transcranial magnetic stimulation (TMS) to identify upper motor neuron involvement in patients with motor neuron disease. BACKGROUND: Diagnosis of ALS depends on upper and lower motor neuron involvement. Lower motor neuron involvement may be documented with electromyography, whereas definite evidence of upper motor neuron involvement may be elusive. A sensitive, noninvasive test of upper motor neuron function would be useful. METHODS: TMS and clinical assessment in 121 patients with motor neuron disease. RESULTS: TMS revealed evidence of upper motor neuron dysfunction in 84 of 121 (69%) patients, including 30 of 40 (75%) patients with only probable upper motor neuron signs and unsuspected upper motor neuron involvement in 6 of 22 (27%) patients who had purely lower motor neuron syndromes clinically. In selected cases, upper motor neuron involvement identified with TMS was verified in postmortem examination. Increased motor evoked potential threshold was the abnormality observed most frequently and was only weakly related to peripheral compound muscle action potential amplitude. In a subset of 12 patients reexamined after 11+/-6 months, TMS showed progression of abnormalities, including progressive inexcitability of central motor pathways and loss of the normal inhibitory cortical stimulation silent period. CONCLUSIONS: TMS provides a sensitive means for the assessment and monitoring of excitatory and inhibitory upper motor neuron function in motor neuron disease.
Adult↗
Eosinophil involvement and serum IgE level in HIV-1-infected children.
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Adolescent↗
A comparative study of nerve healing in adult, neonatal, and fetal rabbits.
This experiment quantitatively compared the human equivalent of a nerve repair following surgical division in the fetal, adult, and early childhood period of development using a rabbit as an experimental animal model. Twelve time-dated pregnant New Zealand White rabbits at 24 days' gestation (term = 31 days) underwent hysterotomy; one hind limb was delivered through the uterine opening. The sciatic nerve was divided and repaired by primary neurorrhaphy using two 11-0 epineural sutures. Sciatic nerve repair was also performed in 10 neonatal and 10 adult New Zealand White rabbits. Following repair, each group was assessed using electromyography examination, measuring distal motor latency and amplitude at 1, 2, 3, and 4 months postrepair. There was no difference in any of the groups in distal motor latency. The amplitude rose incrementally in all groups, and the fetal group had significantly higher amplitudes (p < 0.02) at 1, 2, 3, and 4 months in comparison with the adult group. There was no statistically significant difference between fetal and neonatal nerve repairs at any of the time periods. At the completion of the study, the nerve repair sites were harvested for histologic estimation of mean myelinated fiber density and fiber diameter distribution distal and proximal to the repair site. A greater percentage of myelinated axons crossed the repair site in the fetal group (83 percent) in comparison with the adult group (63 percent) (p < 0.03). Our study also demonstrated significant increases in the number of larger myelinated fibers crossing the repair site in comparison with the neonatal and adult groups (p < 0.04). This study found that fetal nerve healing following surgical repair is superior to that found in adult animals and results in a higher number of larger myelinated fibers crossing the repair site in comparison with adult and neonatal repairs.
Aging↗
Overexpression of glyoxalase-I in bovine endothelial cells inhibits intracellular advanced glycation endproduct formation and prevents hyperglycemia-induced increases in macromolecular endocytosis.
Methylglyoxal (MG), a dicarbonyl compound produced by the fragmentation of triose phosphates, forms advanced glycation endproducts (AGEs) in vitro. Glyoxalase-I catalyzes the conversion of MG to S-D-lactoylglutathione, which in turn is converted to D-lactate by glyoxalase-II. To evaluate directly the effect of glyoxalase-I activity on intracellular AGE formation, GM7373 endothelial cells that stably express human glyoxalase-I were generated. Glyoxalase-I activity in these cells was increased 28-fold compared to neo-transfected control cells (21.80+/-0.1 vs. 0. 76+/-0.02 micromol/min/mg protein, n = 3, P < 0.001). In neo-transfected cells, 30 mM glucose incubation increased MG and D-lactate concentration approximately twofold above 5 MM (35.5+/-5.8 vs. 19.6+/-1.6, P < 0.02, n = 3, and 21.0+/-1.3 vs. 10.0+/-1.2 pmol/ 10(6) cells, n = 3, P < 0.001, respectively). In contrast, in glyoxalase-I-transfected cells, 30 mM glucose incubation did not increase MG concentration at all, while increasing the enzymatic product D-lactate by > 10-fold (18.9+/-3.2 vs. 18.4+/- 5.8, n = 3, P = NS, and 107.1+/-9.0 vs. 9.4+/-0 pmol/10(6) cells, n = 3, P < 0.001, respectively). After exposure to 30 mM glucose, intracellular AGE formation in neo cells was increased 13.6-fold (2.58+/-0.15 vs. 0.19+/-0.03 total absorbance units, n = 3, P < 0.001). Concomitant with increased intracellular AGEs, macromolecular endocytosis by these cells was increased 2.2-fold. Overexpression of glyoxalase-I completely prevented both hyperglycemia-induced AGE formation and increased macromolecular endocytosis.
Acetone↗
Long-term administration of aerosolized pentamidine as primary prophylaxis against Pneumocystis carinii pneumonia in infants and children with symptomatic human immunodeficiency virus infection. The Italian Pediatric Collaborative Study Group on Pentamidine.
SUMMARY: We assessed the long-term feasibility, safety, and tolerability of two regimens of aerosolized pentamidine (AP) as primary prophylaxis of Pneumocystis carinii pneumonia (PCP) in a large sample of infants and children with symptomatic HIV infection in 21 pediatric departments. One hundred forty children were assigned to receive 60 mg every 2 weeks (n = 60) or 120 mg every 4 weeks (n = 80) of AP, delivered by the ultrasonic nebulizer Fisoneb under the supervision of trained personnel. Children underwent monthly clinical and laboratory controls for toxicity and/or development of PCP for an 18-month period. Baseline characteristics were similar in the two treatment groups. The median age was 5 years. The feasibility of administering AP was excellent in 84 (60 percent) and good in 38 (27 percent) children. All children aged <2 years showed excellent or good feasibility. Long-term compliance was good with both regimens. No child had severe adverse reactions requiring discontinuation of the treatment. Cough, sneezing, and bronchospasm were the most frequent side effects occurring, respectively, in 12, 3.7, and 0.7 percent of the 60-mg treatments and in 19.1, 6. 1, and 2.8 percent of 120-mg treatments (p < 0.05). Their incidence was not different in children younger or older than 5 years. Two episodes of PCP were observed in the group receiving 120 mg monthly, whereas none of the 60 children in the biweekly schedule had PCP (p = 0.20). AP can be safely administered to very young children with few adverse side effects.
AIDS-Related Opportunistic Infections↗
Elevation of IgE in HIV-infected children and its correlation with the progression of disease.
BACKGROUND: According to recent data, a switch from a TH1 to a TH2 pattern of cytokines might be a critical step in the progression of human immunodeficiency virus (HIV) infection. Previous studies have demonstrated a disturbance in IgE synthesis in HIV-infected adults. METHODS: Fifty-eight children infected vertically with HIV and 35 children with seroreversion, aged 4 months to 11 years, were evaluated for IgE serum level, CD4+ cell count, skin prick test responses to common airborne and food allergens, individual and family history of atopy, and presence of opportunistic infections. In thirty of the 58 HIV-infected children serum interleukin-4 and interferon-gamma levels were assessed. Thirty-three of the 58 HIV-infected children had a follow-up of 1 year for IgE levels, CD4+ cell count, and occurrence of opportunistic infections and recurrent bacterial infections. RESULTS: Both IgE concentration and the percentage of children with IgE elevation were markedly increased (with no correlation to skin prick test responses or opportunistic infections) in the group of 58 HIV-infected children as compared with the 35 children with seroreversion (p < 0.05). The same parameters were higher in children with acquired immunodeficiency syndrome as compared with children with asymptomatic or mildly symptomatic disease (p < 0.05). Serum interleukin-4 and interferon-gamma levels do not account for IgE hyperproduction. There was a significant association between persistent IgE elevation and severe decline ( > or = 30% over 1 year) in CD4+ counts, as well as increased susceptibility to bacterial infections. CONCLUSIONS: Our study demonstrates a spectrum of IgE dysfunction in children, which is similar to that observed in adults. A persistent IgE hyperproduction appears to be associated with a severe decline in CD4+ cell count, suggesting that this clinical test is a useful marker of disease progression.
Analysis of Variance↗
Pruritic pustular eruption in an infant.
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Eosinophilia↗
Occurrence of infections in children infected with human immunodeficiency virus.
To evaluate the occurrence of infections in asymptomatic and symptomatic human immunodeficiency virus (HIV)-infected children we performed a prospective comparative cohort study. Twenty-seven HIV-infected children were individually matched with paired immunocompetent controls and followed up for a total of 543 months (mean per child, 19.4 +/- 11 months). Collected data were evaluated considering HIV-infected children both as a whole and as P1 and P2 patients according to the Centers for Disease Control classification. Twenty-seven HIV-infected children had 185 infectious episodes vs. 27 matched controls who experienced 118 infections. P1 children had a number of infections similar to those of normal controls (99 vs. 86) whereas P2 children had a significantly higher number of infections than did controls (86 vs. 32). Pneumonia and oral candidiasis occurred significantly more frequently in symptomatic HIV-infected children than in normal controls. Severe infections occurred almost exclusively in HIV-infected symptomatic children.
Child↗
Acute otitis media in human immunodeficiency virus-infected children.
To evaluate the occurrence and outcome of acute otitis media (AOM) in human immunodeficiency virus (HIV)-infected children, a prospective comparative cohort study was performed. Twenty-seven HIV-infected children were individually matched with paired control subjects and followed up for 543 months (mean 19.4 +/- 11). Data collected were evaluated considering HIV-infected children both as a whole and as P1 and P2 patients according to Centers for Disease Control classification. During the observation period, 46 episodes of AOM were diagnosed in 15 HIV patients and 22 in 16 control children: 11 P1 had 27 AOM episodes vs 17 in 13 control children; 6 P2 had 19 AOM episodes vs 5 in 4 control children. Human immunodeficiency virus infection does not seem to modify the occurrence of AOM. Recurrent AOM (3 or more episodes in 6 months) was, however, significantly more common in P2 children. Amoxicillin, to which the bacteria isolated in P2 children were sensitive in vitro, cured 33 of 46 episodes in HIV-infected children compared with 20 of 22 in control children. Cure rate was similar in P1 children compared with control children but was significantly lower in P2 versus control children (47.3% vs 100%). Reasons for higher occurrence of failures in P2 children remain to be investigated.
Acute Disease↗
Synthetic peptides of the hamster beta 2-adrenoceptor as substrates and inhibitors of the beta-adrenoceptor kinase.
1. The beta-adrenoceptor is one of a number of G protein-coupled receptors which have been proposed to contain seven transmembrane alpha-helices. The function of this receptor appears to be regulated by phosphorylation by a specific enzyme, the beta-adrenoceptor kinase. Synthetic peptides which comprise each of the proposed intra- and extracellular domains of the beta 2-adrenoceptor have been tested as potential substrates and inhibitors of the beta-adrenoceptor kinase. 2. Two peptides which encompass the middle and terminal portions of the carboxyl tail of the receptor served as substrates by beta-adrenoceptor kinase. The kinetics of the phosphorylation reaction, however, suggest that these peptides are 10(6)-fold poorer substrate than the agonist occupied receptor. 3. A number of synthetic peptides also served as inhibitors of beta 2-adrenoceptor phosphorylation by beta-adrenoceptor kinase. In particular, a peptide which comprised the first intracellular loop of the beta 2-adrenoceptor (amino acids 56-74) inhibited most effectively with an IC50 of 40 microM. 4. These results suggest that multiple intracellular regions of the beta-receptor may serve as potential sites of interaction with beta-adrenoceptor kinase. Moreover, these regions may serve as potential targets for the development of specific inhibitors of beta-adrenoceptor kinase which could be used to block homologous desensitization.
Amino Acid Sequence↗
Streptococcal pharyngitis in Italian children: epidemiology and treatment with miocamycin.
A prospective multicentre study of Italian children with acute pharyngotonsillitis was carried out to determine the incidence of beta-haemolytic streptococcal infection and its epidemiological characteristics and to evaluate the effectiveness of a recently marketed macrolide, miocamycin. From February 1988 to March 1989, 865 children (aged 5 months to 14 years) were enrolled in 11 paediatric departments. Of these 31.9% had a positive throat culture for beta-haemolytic streptococci (26.6% group A streptococci, 5.3% group B, C, D or F). In 68.1% of the patients the throat culture did not yield any pathogen and the disease was considered to be probably viral. No epidemiological (age, season of occurrence, sex) or clinical characteristics (fever, pharyngeal hyperaemia, exudate etc.) could differentiate children with streptococcal pharyngotonsillitis from those with a probably viral one. Breese's score correctly identified only 19.1% of the cases with group A streptococcal infection. Miocamycin was given 50 mg/kg/day in 2 divided doses for 10 days in 225 children with streptococcal pharyngitis. The drug exhibited good clinical efficacy (resolution or improvement of acute signs and symptoms) in 96.3% of the children and a microbiological efficacy (eradication of the causative bacteria) in 85.3%.
Adolescent↗
[Activity of oral cefroxadin (Oraspor) in childhood infections. Multicentric study of 123 patients].
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Adolescent↗
Effect of miocamycin on theophylline kinetics in children.
The interaction between a new macrolide antibiotic, miocamycin, and theophylline was evaluated in a single cross-over study in 5 asthmatic children. Each patient received a single dose of theophylline (4.3 mg/kg) delivered in 15 min using a constant-rate infusion pump, immediately before and after a 10 day course of miocamycin 17.5 mg/kg b.d. The pharmacokinetics of theophylline were calculated for each phase of the study. The elimination rate constant (3.92 vs 3.74 h-1), the mean total body clearance (1.71 vs 1.8 ml X min X kg-1) and the mean apparent volume of distribution (0.57 vs 0.581 X kg-1) did not differ. The result can be explained by the inability of the antibiotic to form inactive cytochrome P-450 metabolite complexes which can interfere with the metabolism of theophylline. Thus, miocamycin can safely be administered to asthmatic children requiring theophylline treatment, when they have an infection due to susceptible pathogens.
Asthma↗
Effect of miocamycin on theophylline kinetics in asthmatic children.
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Asthma↗
Placebo-controlled double-blind food challenge in asthma.
To determine the prevalence of food allergy as a cause of exacerbation of asthma, we studied 300 consecutive patients with asthma (7 months to 80 years of age) who attended a respiratory clinic. Each patient was screened for possible food allergy by means of a questionnaire and by skin prick tests with the six food allergens most common in our area. Patients with either a suggestive history and/or a positive prick test and/or RAST underwent double-blind food challenge with lyophilized food in capsules or food mixed in a broth to disguise its taste. Pulmonary function tests and symptoms were followed for 8 hours after each challenge. Of the 300 patients screened, only 25 had either a history or skin prick tests or RAST responses suggestive of food allergy. Twenty patients had interpretable food challenges. In these 20 patients, food challenge caused asthma in six and caused other symptoms (atopic dermatitis and gastrointestinal symptoms) in five. On rechallenge after pretreatment with disodium cromoglycate (300 mg 30 minutes before the food challenge), the asthmatic response was blocked in four of five subjects. The patients with asthma with food allergy were generally young, had a current or past history of atopic dermatitis, and high total serum IgE levels. Our findings confirm that food allergy can elicit asthma, but its incidence is low, even in the population attending a specialty clinic. Food elimination diets should not be prescribed for all patients reporting an adverse reaction to foods or having a positive skin prick test and/or RAST with food allergens. In patients with asthma caused by food allergy, disodium cromoglycate may be used to complement elimination diets.
Adolescent↗