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Biomedical subjects

G Bruno

Publications and source records attributed to G Bruno.

At least 109 records · Page 6Linked to original sources

Natural history of IgE antibodies in children at risk for atopy.

BACKGROUND: The relationship between atopic diseases and high serum IgE levels has been emphasized since the mid-sixties, when IgE antibodies were discovered. A number of environmental factors, such as the type of feeding, passive smoking, viral infections, early mold, house dust mite and pet fur exposure modulate IgE synthesis and affect the development of atopic diseases. OBJECTIVE: The aim of the present study was to investigate the natural history of total and specific IgE antibodies in babies at risk for atopy, enrolled in a prospective study for the prevention of atopic disease, and follow-up from birth to 4 years of age. METHODS: One hundred seventy-four babies (90 boys and 84 girls) at risk for atopy were enrolled in this study. At the last follow-up the children had a median age of 52 months (range 43 to 74 months), dietary and environmental manipulations for the prevention of atopic diseases were recommended. All the infants were examined at the ages of 1, 3, 6, 9, and 12 months and twice each year subsequently when detailed histories were taken and signs and symptoms of atopic disease were sought. Total and specific IgE to cow milk, egg, soy, wheat, and Dermatophagoides pteronyssinus (Dpt) were measured at 6 and 12 months of life and then every year. RESULTS: During the first 24 months of life, the number of children with specific IgE to foods (n = 30) was significantly higher in comparison to the number of children with specific IgE to Dpt (n = 12) (P = .0006). Cow milk and egg were the most common offending foods. The number of children with IgE to cow milk (n = 14) was significantly higher than that with IgE to soy (n = 9) (P = .0011). Total serum IgE levels were significantly higher in the group of children who developed atopic disease in comparison with the group that did not (P < .01). CONCLUSION: Dietary and environmental measures may influence the IgE response in atopy-prone children, thus confirming the role of environmental factors in the modulation of the phenotypic expression of atopy.

Allergens↗

Acetyl-L-carnitine in Alzheimer disease: a short-term study on CSF neurotransmitters and neuropeptides.

Acetyl-L-carnitine (ALCAR) is a drug currently under investigation for Alzheimer disease (AD) therapy. ALCAR seems to exert a number of central nervous system (CNS)-related effects, even though a clear pharmacological action that could explain clinical results in AD has not been identified yet. The aim of this study was to determine cerebrospinal fluid (CSF) and plasma biological correlates of ALCAR effects in AD after a short-term, high-dose, intravenous, open treatment. Results show that ALCAR CSF levels achieved under treatment were significantly higher than the ones at baseline, reflecting a good penetration through the blood-brain barrier and thus a direct CNS challenge. ALCAR treatment produced no apparent change on CSF classic neurotransmitters and their metabolite levels (homovanillic acid, 5-hydroxyindoleacetic acid, MHPG, dopamine, choline). Among CSF peptides, while corticotropin-releasing hormone and adrenocorticotropic hormone remained unchanged, beta-endorphins significantly decreased after treatment; plasma cortisol levels matched this reduction. Since both CSF beta-endorphins and plasma cortisol decreased, one possible explanation is that ALCAR reduced the AD-dependent hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity. At present, no clear explanation can be proposed for the specific mechanism of this action.

Aged↗

Pirenzepine decreases basal and stimulated GH secretion in patients with type 2 (non-insulin-dependent) diabetes mellitus.

Growth hormone (GH) hypersecretion has been described in diabetes mellitus and seems to be involved in the pathogenesis of diabetes complications. As pirenzepine (PZ), a cholinergic muscarinic antagonist, is able to inhibit GH hypersecretion in insulin-dependent diabetes mellitus (IDDM), we investigated whether PZ is also able to inhibit spontaneous and stimulated GH-release in non-insulin-dependent diabetes mellitus (NIDDM). Ten non-obese well-controlled patients with NIDDM underwent in random order the following three double-blind one week treatments: placebo (PL), PZ at low dose (PL in the morning plus PZ 50 mg at 22 h) or high dose (PZ 50 mg at 8 h plus 100 mg at 22 h). Pirenzepine administration significantly (p < 0.05) decreased nocturnal GH release after both low and high dose (AUC, PL vs PZ: 107.3 +/- 26.5 vs 48.3 +/- 10.5 and 57.6 +/- 9.6 micrograms/L/h, respectively). The GH response to arginine infusion was significantly inhibited by PZ at high dose (AUC, 147.1 +/- 48.8 vs 444.7 +/- 194.3 micrograms/L/h, p < 0.01), but not at low dose. Glucose, insulin, glucagon and somatostatin responses to arginine infusion were not changed by pirenzepine treatment. In conclusion, the muscarinic blockade by PZ is able to inhibit the spontaneous and stimulated GH secretion also in NIDDM without affecting insulin secretion.

Adult↗

IgG subclass antibodies against Parietaria judaica in normal and allergic subjects.

IgG antibody response to the inhalant allergen Parietaria judaica (Pj) and IgG subclass distribution were studied in 82 normal subjects, divided into three groups according to age (0-1, 1-20, and 20-60 years) and in 32 allergic subjects aged 20-60 years. Both normal and allergic subjects showed an IgG response, and all had IgG1 antibodies specific for PjE. Serum IgG2, IgG3, and IgG4 against PjE were detectable in 36%, 46%, and 22% of normal subjects, and in 58%, 31%, and 65% of allergic subjects, respectively. A significant difference in class distribution between allergic and age-matched normal subjects was found only for IgG4 antibodies against PjE (65% and 17%; P < 0.01). The ELISA results were also analyzed quantitatively, taking into account the relative proportion of specific antibodies. Thus, in normal subjects IgG1 antibodies showed a decreasing trend as the age rose, while no differences according to the age of the subject were found for IgG2 and IgG4. When data from allergic subjects (20-60 years) and the age-matched normal group were compared, they were different for the relative percentage of IgG2 only, showing for this a significantly lower value (P < 0.001). The present data indicate that normal and allergic subjects show differences in the IgG isotype distribution depending on their sensitivity and duration of allergen exposure.

Adolescent↗

Prevalence and clinical features of known type 2 diabetes in the elderly: a population-based study.

In a large population-based survey, 1947 Type 2 diabetic subjects aged 40 yr and over were identified, with high ascertainment (91%). Age-specific prevalence increased from 2.48% in the age group 40-64 to 5.62% in the age group > or = 65 yr; 35% of subjects were 65 yr and over at the onset of the disease. Elderly diabetic subjects showed a significantly (p < 0.001) lower frequency of family history of diabetes (26% vs 42%), obesity at diagnosis (62% vs 70.6%) and fasting plasma glucose (FPG) (8.3 +/- 2.4 vs 8.1 +/- 2.8 mmol l-1). Elderly diabetic subjects were more commonly managed by general practitioners (GPs) (29.7% vs 21.5%). Elderly patients attending only the GPs differed in FPG, which was significantly lower (7.9 +/- 2.1 nmol l-1 vs 8.5 +/- 2.6 mmol l-1). Good metabolic control (FPG < 6.6 mmol l-1) was found in 17.5% of subjects in the age group 40-64 and in 22.9% in the age group > or = 65 yr. Poor metabolic control was more commonly seen in those attending the diabetic clinic. HBA1c measurement was available in 32.0% of the elderly attending the diabetic clinic and in only 10.7% of those in the care of GPs. Fundal examination was available in 48.2% and in 36.5%, respectively, of diabetic subjects in the age groups 40-64 > or = 65 yr, without differences between those attending and those not attending the diabetic clinic.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

National diabetes programs. Application of capture-recapture to count diabetes?

OBJECTIVE: To evaluate the utility of capture-recapture methods using multiple, routinely collected, computerized data sources to estimate the numbers and prevalence of diabetes. Methods employed for regional and national monitoring of diabetes have been too inaccurate or too expensive. RESEARCH DESIGN AND METHODS: A survey was undertaken that used four sources of ascertainment to identify prevalent cases of known diabetes in community of Northern Italy: diabetic clinic and family physicians, hospital discharges, prescriptions, and reagent strips and insulin syringes. Capture-recapture methods were employed to estimate the number of missing cases and to adjust for undercount to accurately estimate the number of people who had diabetes. RESULTS: We identified 2,069 unique prevalent cases of known diabetes with the intensive case-finding procedure. The diabetic clinic and family physicians data source identified the largest number of cases. The evaluation of the two sample capture-recapture estimates showed that they were all biased downward because of dependencies between sources. Log-linear modeling was employed to take into account the dependence among all data sources and the heterogeneity of diabetic patients. This method estimated that 2,586 cases existed, resulting in an ascertainment-adjusted prevalence of 2.77% (95% confidence interval, 2.44-3.10). Thus, despite the active case identification, approximately 20% could not be identified. However, the number of cases and rates could easily be adjusted using capture-recapture. CONCLUSIONS: The study shows that a two-sample capture-recapture estimate could be very biased if the investigator is not assured that the sources are independent. However, if at least three data sources are employed, log-linear models allow estimation of the number and prevalence rate adjusted for the degree of undercount (in spite of both the dependence of data sources and the heterogeneity of the diabetic population). The critical factor, however, is that the application of multiple sources with capture-recapture methods could be applied across broad geographical areas and across time to have cost-effective monitoring of diabetes at local and national level.

Adolescent↗

High-performance liquid chromatographic assay for N2-[5-(hypoxanthin-9-yl)pentyloxycarbonyl]-L-arginine (ST 789) in plasma by cyclization with benzoin and fluorimetric detection.

This paper describes a new highly sensitive assay for N2-[5-(hypoxanthin-9-yl)pentyloxycarbonyl]-L-arginine, an immunomodulatory agent, required for clinical pharmacokinetic investigation. A pre-column derivatization by cyclization with benzoin in aqueous medium produces the fluorescent 2-substituted amino-4,5-diphenylimidazole fluorescing at 450 nm (excitation wavelength 310 nm). L-Arginine-acetyl-L-carnitinamide chloride (ST 857, II), another arginine derivative, was used as an internal standard. A C18 DB column (5 microns, 250 mm x 4.6 mm I.D.) and a 45:55 (v/v) mixture of 0.05 M ammonium phosphate at pH 7.2 and methanol as mobile phase were used. Linearity was ascertained in the range 5-100 ng. Extraction recovery from plasma proved to be higher than 90% in the range 5-50 ng/ml. Intra-day precision, expressed as coefficient of variation, was in the range 4.7-6.0%. The limit of quantification proved to be 5 ng/ml and the limit of detection 2 ng/ml at a signal-to-noise ratio of 5. The method is specific.

Adjuvants, Immunologic↗

Disease monitoring.

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Epidemiologic Methods↗

Allergenicity of milk protein hydrolysate formulae in children with cow's milk allergy.

Cow's milk protein hydrolysate formulae have been developed to lower or eliminate the allergenicity of cow's milk proteins, and to reduce the antigenic load and the risk of sensitization. Cross-reactivity between different hydrolysate formulae and cow's milk proteins has been demonstrated. We have studied 20 children (median age 31 months, range 15-76 months) with a history of IgE-mediated cow's milk allergy. All the children had immediate allergic respiratory and/or cutaneous and/or gastro-intestinal reactions to cow's milk ingestion. In addition, the children had positive prick skin tests and positive RAST to cow's milk. Prick skin test, RAST, and double-blind placebo controlled food challenges were performed with three different hydrolysate formulae: a casein hydrolysate formula and two whey formulae, one partially and one extensively hydrolyzed. All 20 children had immediate allergic reactions after the challenge test with cow's milk. Only 2/20 children had a positive challenge test with a casein hydrolysate formula (Alimentum): one developed asthma and one urticaria. Two of the 15 children challenged with an extensively hydrolysed whey formula (Profylac) developed perioral erythema. Nine out of 20 children had a positive challenge test with a partially hydrolysed whey formula (Nidina H.A.): four developed asthma, three urticaria and two lip oedema. All children had positive prick skin tests to cow's milk proteins (casein and/or lactalbumin); 9 to Nidina H.A.; 3 to Profylac, and 3 to Alimentum. Specific IgE antibodies to cow's milk were present in all children; in 13 to Nidina H.A., in 4 to Profylac, and in 3 to Alimentum.

Allergens↗

Prevention of cyclophosphamide-induced diabetes in the NOD/WEHI mouse with deoxyspergualin.

Ten out of 20 (50%) 17-week-old female NOD/WEHI mice developed an acute form of autoimmune diabetes when injected with two large doses of cyclophosphamide (CY), given at 14-day intervals. If these mice were treated under a prophylactic regimen with 2.5 mg/kg body weight per day of the novel immunosuppressant deoxyspergualin (DSP) the onset of diabetes was completely prevented. Moreover, DSP-treated animals showed reduced signs of pancreatic insulitis, had lower percentages of splenic lymphoid cells (SLC) expressing IL-2 receptors and Ly-6C antigens on their surfaces, and these cells released lower amounts of interferon-gamma (IFN) when stimulated in vitro. These data, providing evidence for the capacity of DSP to protect NOD/WEHI mice from experimental autoimmune diabetes and to modulate histo-immunological pathogenic pathways, indicate DSP as a drug of potential interest in the treatment of human insulin-dependent diabetes mellitus.

Animals↗

Sex differences in incidence of IDDM in age-group 15-29 yr. Higher risk in males in Province of Turin, Italy.

OBJECTIVE: To report the incidence of IDDM in the age-group 0-29 yr in the Province of Turin, Italy (951, 445 inhabitants 0-29 yr of age), over a 5-yr period (1984-1988) according to age, sex, and geographical region within the area and to identify any temporal trend. RESEARCH DESIGN AND METHODS: The survey used as the primary data source the list of all patients attending diabetic clinics, and as secondary data source, used the list of hospital discharges for diabetes. RESULTS: We identified 298 incident cases of IDDM in people 0-29 yr of age. Estimated completeness of ascertainment of the registry was 97%. Age-adjusted (world-standard) incidence rates were 7.40/100,000 (95% CI 6.28-8.71), 5.83 (4.95-6.86), and 6.70 (5.97-7.51), respectively, in the age-groups 0-14, 15-29, and 0-29 yr. Incidence was significantly higher in males than in females in the age-group 15-29 yr (7.36, 6.02-8.98, vs. 4.21, 3.12-5.56). An increasing incidence from rural areas to the greater Turin area (city and its industrial belt) was evident. No significant temporal trend during the study period was found, although year-to-year variability was evident, with the highest incidence in 1984. CONCLUSIONS: This study suggests a high male-to-female ratio of incidence of IDDM after 14 yr; either sex hormones or different exposure to environmental determinants could be involved.

Adolescent↗

Counting diabetes in the next millennium. Application of capture-recapture technology.

Monitoring diabetes is critical for our understanding of the etiology and natural history of disease and for public health actions. However, traditional methods for monitoring are either too expensive (e.g., IDDM registries, NIDDM-OGTT prevalence surveys) or too inaccurate (routinely collected data or passive surveillance) for broad accurate, national programs for monitoring the incidence and prevalence of disease. We suggest that one technology called capture-recapture would considerably increase our ability to "count" diabetes, both nationally and globally. Implementation of this approach could lead to accurate inter- and intracountry data on rates of disease. Moreover, such tracking of diabetes could serve as the model for the monitoring of all disease in the 21st century and beyond.

Animals↗

Hemangioendothelioma mimicking a median nerve neoplasm. Case report.

The authors report a case of brachial vein epithelioid hemangioendothelioma resembling a median nerve neoplasm clinically and radiologically. It was found as a mass closely attached to median nerve and arising from one of two brachial veins. Simple resection, requiring sacrifice of the vein, allowed nerve median sparing but recurrence occurred one year later. Hemangioendothelioma should be also considered in differential diagnosis and in the planning surgery of arm median nerve masses. Wide local excision is surgical treatment recommended in those cases when regional lymph nodes or systemic metastasis have not been recognized. Regional lymph nodes resection and adjunctive radiation and chemo-therapy should be considered only for "malignant" or metastatic hemangioendothelioma.

Diagnosis, Differential↗

Evaluation of 2-(2-thiophenecarboxy)benzoic acid and related active metabolites in biological samples.

This paper describes a quantitative assay of 2-(2-thiophenecarboxy)benzoic acid and its systemic metabolites, namely salicylic acid and thiophenecarboxylic acid, by high-performance liquid chromatography with ultraviolet detection at 254 nm. Analytes were extracted from acidified samples with tert.-butylmethyl ether and separated with an RP-18 column (150 mm x 3 mm I.D., 5 microns particle size) with a mixture of 0.01 M potassium phosphate and methanol (70:30, v/v) at pH 3.1. The method proved to have the validation required for pharmacokinetic investigations in animals and humans.

Animals↗

A population-based prevalence survey of known diabetes mellitus in northern Italy based upon multiple independent sources of ascertainment.

The aims of this survey were (1) to estimate the prevalence of known diabetes mellitus in 1988 in Casale Monferrato (Northern Italy); (2) to validate different data sources available in Italy; (3) to identify a population-based cohort of diabetic patients. Multiple independent data sources were used and the capture-recapture method was applied to estimate the completeness of ascertainment of the survey. The primary data source was the list of all patients attending the diabetic clinic or those referred by family physicians and paediatricians of the area. The secondary data sources were the list of hospital discharges, the prescriptions data source and the list of all people using reagent strips and insulin syringes. On 1 October 1988 (the cut-off date) 2,069 cases of known diabetes were identified. The estimated completeness of ascertainment of the survey was 91%. Prevalence of known diabetes, Type 1 (insulin-dependent), Type 2 (non-insulin-dependent) and insulin-treated diabetes were, respectively, 2.21% (95% CI 2.13-2.29), 0.80/1,000 (0.62-0.98) and 2.10% (2.01-2.19), 2.92/1,000 (2.57-3.27). A higher prevalence of Type 2 diabetes was observed in women (2.30%, 2.18-2.42) than in men (1.88%, 1.76-2.00). Age-specific prevalence of Type 2 diabetes increased with age. Computerized data sources routinely available in the Piedmont Region (hospital discharges and prescriptions data sources) showed a low completeness of ascertainment when considered together (65%, 1,338 of 2,069), indicating the need to involve the diabetic clinic and family physicians in the ascertainment of known diabetes. In conclusion, the prevalence of known diabetes in Italy was lower than in Northern Europe and the United States.

Adolescent↗

Pharmacokinetics of 2-(alpha-thenoylthio)-propionylglycine (TTPG) in healthy volunteers--an oral dose-proportionality investigation.

The dose linearity of 2-(alpha-thenoylthio)-propionylglycine (TTPG) pharmacokinetics after a single oral administration at three different TTPG doses (180, 540 and 1080 mg) was evaluated in 12 healthy volunteers according to an open, randomized, cross-over study with a 1-week wash-out period between each administration. The duration of the study, for each subject, was 4 weeks. Plasma concentration and urinary excretion of TTPG and its two systemic metabolites, namely propionylglycine (tiopronin) and thiophenecarboxylic acid (TCA) were assayed by a previously well validated HPLC method. Due to differences in the physical and chemical properties of these compounds, two assays were needed, one to measure TTPG and TCA as such, and one to measure derivatized tiopronin. Both used UV detection. TTPG, tiopronin and TCA were quickly detected in plasma, suggesting that the drug administered is rapidly absorbed and biotransformed, in part, in the systemic circulation into the two metabolites noted above. Time-to-peak for all three analytes showed a trend to increase with increasing doses of TTPG, being: 0.42, 0.40 and 0.67 h (P < 0.01) with TTPG; 0.53, 0.47 and 0.73 h (P < 0.05) with TCA; and 1.33, 2.13 and 2.58 h (P < 0.01) with tiopronin. Cmax showed the opposite behaviour with values (ng ml-1) normalized to the dose of 540 mg: 1235, 905 and 513 (P < 0.001) with TTPG; 888, 547 and 383 (P < 0.001) with TCA; and 7290, 6950 and 5170 (P < 0.01) with tiopronin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗