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Biomedical subjects

D Leduc

Publications and source records attributed to D Leduc.

36 records · Page 2Linked to original sources

Guinea-pig treatment with pertussis toxin suppresses macrophage-dependent bronchoconstriction by fMLP and fails to inhibit the effects of PAF.

1. Bronchoconstriction and thromboxane B2 (TxB2) release following the intra-tracheal administration of the secretagogue N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) to lungs from pertussis toxin-treated guinea-pigs in vivo and in vitro were inhibited as compared to saline-treated animals, under conditions where the responses to PAF were modified less effectively. 2. The cell target accounting for bronchoconstriction by fMLP and for inhibition by pertussis toxin is located in the airways and is probably the alveolar macrophage. Indeed (a) fMLP-induced superoxide anions and TxB2 formation by alveolar macrophages were inhibited by pertussis toxin given in vivo; (b) Gi proteins of membranes from alveolar macrophages were ADP-ribosylated in vivo by pertussis toxin and (c) bronchoconstriction and TxB2 release in response to the intra-tracheal administration of fMLP to lungs from pertussis toxin-treated animals were restored when alveolar macrophages from control guinea-pigs were transferred into the airways of pertussis toxin-treated animals before lung isolation. 3. Pertussis toxin administered to guinea-pigs in vivo, reduced the subsequent TxB2 formation and superoxide anion release by alveolar macrophages stimulated with PAF, but failed to inhibit PAF-induced bronchoconstriction. 4. Formation of TxB2 by alveolar macrophages following the intra-tracheal administration of fMLP accounts for bronchoconstriction and requires pertussis toxin-sensitive Gi proteins. PAF operates via a different mechanism, which is independent of Gi-like protein and involves mediators other than TxB2 and superoxide anions.

Adenosine Diphosphate Ribose

Effect of human recombinant interleukin-5 on in vitro responsiveness to PAF of lung from actively sensitized guinea-pigs.

1. The intra-tracheal (i.t.) administration of human recombinant interleukin-5 (rhIL-5; 100 or 300 ng) to isolated perfused lungs from guinea-pigs actively sensitized to ovalbumin induced an increased bronchoconstriction and release of thromboxane A2 (TXA2) and histamine into the lung effluent following the subsequent (10 min) intra-arterial injection of platelet-activating factor (PAF). Lung responses to 5-hydroxytryptamine were unaffected by rhIL-5. 2. Hyperresponsiveness to PAF was observed when the lungs were obtained from guinea-pigs used 2 or 7 days after a booster injection of the antigen and, to a lower extent, when they were from animals sensitized by a single antigen administration. By contrast, rhIL-5 did not modify the responses to PAF of lungs from passively sensitized or from adjuvant-treated guinea-pigs, suggesting that immunological stimulation is required to allow the expression of synergism between rhIL-5 and PAF. 3. Guinea-pigs killed 2 and 7 days after the booster injection of the antigen exhibited a marked increase in the number of eosinophils in the bronchoalveolar lavage fluid (BAL), as compared to non-sensitized animals. 4. Our results demonstrate that rhIL-5 and PAF act synergistically to induce enhanced bronchoconstriction and mediator release exclusively when lungs are obtained from guinea-pigs sensitized once to ovalbumin and then boosted. Since recruitment of eosinophils into the airways and the development of hyperresponsiveness to PAF are concomitant, it is suggested that eosinophils are the target cells for interaction between rhIL-5 and PAF.

Animals

Acute and long term respiratory damage following inhalation of ammonia.

A lifelong non-smoker who was the victim of a massive accidental exposure to anhydrous ammonia gas was followed up for 10 years. In the acute phase the patient presented with severe tracheobronchitis and respiratory failure, caused by very severe burns of the respiratory mucosa. After some improvement he was left with severe and fixed airways obstruction. Isotope studies of mucociliary clearance, computed tomography, and bronchography showed mild bronchiectasis. It is concluded that acute exposure to high concentrations of ammonia may lead to acute respiratory injury but also to long term impairment of respiratory function.

Accidents, Occupational

Risks of flumazenil in mixed benzodiazepine-tricyclic antidepressant overdose: report of a preliminary study in the dog.

This preliminary study evaluates the cardiac and neurological risks associated with the sudden antagonism of benzodiazepine (BZD)--induced sedation in dogs intoxicated with tricyclic anti-depressants (TCA). Twelve dogs were anesthetized with midazolam and ventilated with room air. EEG, ECG, and arterial pressure were continuously recorded. An infusion of amitriptyline (6 dogs) or clomipramine (6 dogs) 1 mg/kg. min was maintained until signs of cardiotoxicity (QRS prolongation, hypotension or arrhythmias) occurred. The effects of a bolus of flumazenil 0.2 mg/kg were then observed until 120 minutes. In amitriptyline poisoning, BZD reversal was associated with development of convulsions in 3 dogs, with severe arrhythmias in 4 and with one death. In clomipramine intoxication, 2 dogs developed sudden fatal arrhythmias. These results show that BZD reversal may unmask the convulsant properties and increase the severity of arrhythmias induced by TCA.

Amitriptyline

The crying of infants with colic: a controlled empirical description.

To obtain a controlled empirical description of some of the measurable clinical features of colic in a naturalistic context, 38 infants whose mothers considered crying a problem ("colic") and 38 pair-matched control infants were observed and videotaped at home 10 minutes before and after an evening feed. The parents kept a diary of infant behaviors (including crying and fussing) for 7 days following the visit. Following Wessel et al (Pediatrics. 1954;14:421-434), each "colic" infant was classified according to the number of days per week that crying and fussing duration was greater than 3 h/d. The distribution of infants with colic suggested that there were two subgroups: Wessel's colic infants, with 3 days or more per week of more than 3 hours of crying and fussing per day; and non-Wessel's colic infants, with fewer such days. Maternal measures of total daily crying/fussing duration, crying/fussing bout length, and infant temperament and objective analyses of facial activity showed a consistent pattern of differences in which Wessel's colic infants differed from both non-Wessel's colic and control infants, who in turn did not differ from each other. Both colic groups differed from control infants only in the perception of postfeed cries as being more "sick sounding." The results imply that the complaint of colic represents two (or more) groups and that there may be meaningfully distinct colic syndromes. They also provide the first independent empirical support for Wessel and colleagues' clinical distinction between "fussy" and "contented" babies.

Colic

Reliability of self-reports of alcohol use by community clients.

Eighty-five of 116 randomly selected clients receiving case management services at a comprehensive community mental health center responded anonymously to a survey questionnaire that included two measures of self-reported alcohol use: questions about frequency and quantity and a retrospective diary for reporting the number of drinks consumed daily in the preceding week. Forty-two patients reported using alcohol; consumption was higher among younger patients. A significant correlation was found between responses to the frequency-quantity questions and the information provided in the retrospective diary, indicating that self-reports of alcohol consumption are reasonably reliable for the clients studied. Future research is needed to establish the reliability and validity of self-reported alcohol and drug use in typical treatment settings.

Affective Disorders, Psychotic

Feeding and temperament as determinants of early infant crying/fussing behavior.

In the first 3 months of life, crying and fussing in normal infants tend to increase until 6 weeks of age and decrease progressively thereafter. To determine whether feeding choice and early infant temperament are predictors of early crying, 374 healthy, full-term infants were observed prospectively from birth to 6 weeks of age. Feeding choice and sociodemographic characteristics were ascertained in the first few days postpartum. Parents completed a 17-item early infant temperament questionnaire at 2 weeks of age and a 24-hour behavior diary for 8 days at 6 weeks of age. Initially breast-fed infants cried and fussed more frequently throughout 24 hours compared with those who were formula fed, and increased frequency and duration of crying and fussing were predicted by "more difficult" temperament. Furthermore, a different pattern of crying and fussing within the day was found for infants who were changed from breast- to formula feeding. However, according to stepwise multiple regression models, daily duration of crying/fussing was significantly predicted only by the temperament score (but not initial feeding choice), which accounted for 7% of the variance. Frequency of crying/fussing were predicted only by socioeconomic status, temperament, and feeding frequency, which accounted for 12% of the variance. Breast- or formula feeding at 6 weeks of age was independently associated with crying/fussing only during the evening. It was concluded that early infant temperament predisposes to early crying and fussing but is of limited use as a clinical predictor. Later crying/fussing behavior is not predicted by initial feeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Bottle Feeding

[Alveolar microlithiasis. A study of minerals in the lung].

A pulmonary scintigraph of pyrophosphate was performed to assess calcium metabolism in a man of 39 with alveolar microlithiasis, as was histologic study with a mineral analysis of wave-length dispersion and an analysis crossing the microliths enclosed in the resin. Two treatments were tried without success: First with diphosphonates and then alveolar lavage.

Adult

Diffusion of ofloxacin into the cerebrospinal fluid in patients with bacterial meningitis.

Ofloxacin diffusion into cerebrospinal fluid (CSF) was evaluated in nine patients with bacterial meningitis. Patients were under treatment with i.v. amoxicillin (100 mg/kg/day), and during the first five days they were also given oral ofloxacin, 200 mg b.i.d. On days 2 and 5, blood and CSF samples were collected for assays by both HPLC and microbiological techniques. Samples were obtained 2 h (n = 2), 4 h (n = 1), 6 h (n = 2), 8 h (n = 2) and 12 h (n = 2) after the ofloxacin dose respectively. Concentration in CSF was 50 to 60% of that in serum and there was no significant difference between results with the two assay techniques.

Adult

Preliminary characterization of inhibitors of Neisseria gonorrhoeae produced in vitro by Eubacterium limosum.

Among anaerobic bacteria normally found in the urogenital flora, Eubacterium limosum was found to inhibit the in vitro growth of Neisseria gonorrhoeae. The antigonococcal activity produced by E. limosum was soluble in methanol and in a chloroform--methanol mixture (30:70). The fraction soluble in chloroform--methanol (30:70) yielded eight absorbance peaks when chromatographed on Bio-Gel P-2 and the inhibitory activity was found in the first two peaks. This activity was not absorbed on DEAE Sephacel and was eluted with distilled water in a peak considered as peak 1, on which preliminary characterization was done. The inhibitory activity of peak 1 was found to be heat and pH resistant and not susceptible to proteases, lipase, or amylases. When peak 1 was chromatographed on cellulose paper using a butanol--acetic acid (4:1) solvent system, eight different spots were detected upon spraying the paper with ninhydrin. No spot was detected with anthrone, bromothymol, nor Sudan black reagents used for the detection of carbohydrates and lipids. Based on sodium dodecyl sulfate-urea polyacrylamide gel electrophoresis and gel chromatography on Sephadex G-25, peak 1 appeared either as a diffuse band and as a single peak, respectively. The molecular weight of the inhibitory complex was estimated to be 2400. All these results suggest that the antigonococcal activity produced by E. limosum is composed of more than one low molecular weight amino compound.

Bacteriocins

A computerized recall system for office practice.

A computerized system that has been in use in a small group practice since 1980 is described. Although many pediatricians have begun to use personal computers in office practice, most accounts of their experience to date relate primarily to the role of computers in facilitating administrative tasks, such as billing. The procedures involved in establishing the system are described, along with details about the nature of the programming concepts and several of the most important applications. A particular focus was to enable the computer to be used to improve the follow-up of patients with problems requiring recall visits, eg, immunizations. The results indicate that the percent of patients judged to be overdue for immunizations fell from 15.4% prior to the introduction of the computer to 1.3% and 4.3%, respectively, in the following 2 years. The proportion of children with other health problems requiring follow-up, 44.5% of the entire active practice population are also described. It is concluded that the computerized system can enhance the quality of patient care and greatly facilitate office-based research.

Appointments and Schedules

Oxidant radical release by alveolar macrophages after cadmium chloride exposure in vitro.

Chronic exposure to cadmium can cause lung emphysema, the mechanism of which is unknown. Current concepts on the pathogenesis of emphysema largely emphasize the role of a protease-antiprotease imbalance. The aim of this work was to study the effects of cadmium on the regulation of antiprotease activity and the release of oxidant radicals from alveolar macrophages. Guinea pig alveolar macrophages (AM) were exposed overnight to cadmium chloride (CdCl2) in vitro. To define the cytolytic threshold dose, cell lysis was evaluated by trypan blue exclusion and lactate dehydrogenase release. Non-cytolytic concentrations were then used (0.1, 0.4 and 0.8 ppm) to simulate chronic exposure conditions. Overnight exposure to 0.1, 0.4 and 0.8 ppm CdCl2 decreased intracellular ATP (mean +/- SD: 91 +/- 8%, 72 +/- 7%, 50 +/- 8% of control cells, respectively), suggesting that even at non-cytolytic doses, Cd2+ can cause cell injury. The assessment of oxygen radical release from AM after overnight exposure to CdCl2 showed a dose-dependent decrease to 54.3 +/- 8.2%, 32.2 +/- 4.3% and 25 +/- 3% of control after exposure to 0.1, 0.4 and 0.8 ppm Cd2+, respectively. At non-cytolytic concentrations (0.1, 0.4 and 0.8 ppm) CdCl2 did not decrease alpha 1-proteinase inhibitor activity either in the absence of AM or in the presence of AM and myeloperoxidase. In conclusion, our in vitro results do not suggest that a protease-antiprotease imbalance is involved in the pathogenesis of cadmium-induced emphysema.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate

[Clinical study of 105 cases of isolated weight loss in internal medicine].

We arbitrarily define "isolated weight loss" as the loss of at least 10 p. 100 of body weight over less than one year, without any single cause being disclosed by questioning, physical examination and such paraclinical examinations as blood electrolytes, blood count and differential, routine dipstick urinalysis and X-ray of the chest. Among the 105 patients we studied, the causes of isolated weight loss were: (1) psychic disorders (chiefly depression) in 60 p. 100 of the cases; (2) a variety of organic diseases in 29 p. 100, including gastrointestinal diseases (8 p. 100), cardiovascular and respiratory diseases (6 p. 100), Horton's disease (4 p. 100), Portuguese amyloidosis (1 p. 100), unexplained inflammatory syndrome (1 p. 100), endocrine disease (hyperthyroidism, 4 p. 100) and intoxication with medicines, alcohol or heroin (5 p. 100); (3) no definite cause could be found in 11 p. 100 of the cases. We suggest a diagnostic approach involving a limited number of examinations, viz.: erythrocyte sedimentation rate, measurement of transaminases, gamma GT and alkaline phosphatase enzymes, abdominal ultrasonography and ultra-sensitive TSH assay. We consider it important to switch from useless paraclinical tests to the detection and management of psychic disorders. Weight loss is a frequent motive of consultation, but its diagnostic value is often misunderstood. The purpose of this study was to provide data for the artiological diagnosis of isolated weight loss--a relatively frequent problem in internal medicine.

Adult

Effect of PK11195 on cardiovascular toxicity due to verapamil: an experimental study in the dog.

In vitro studies have suggested that peripheral binding sites (PBR) for benzodiazepine (BZD) could be coupled to the voltage operated calcium channel (VOC) in the heart and that PK11195, an non-BZD ligand with antagonistic activity at this receptors, could inhibit the electrophysiological and mechanical properties of both "peripheral" benzodiazepines and calcium channel blockers. This study evaluates the antidotal value of PK11195 against the cardiovascular depression and arrhythmias in a canine model of acute verapamil intoxication. Although sinus activity is more often preserved or restored (7/8 vs 1/6) in the animals treated with PK11195, this compound, administered in doses able to saturate heart PBR, is unable to prevent or correct the haemodynamic alterations induced by acute verapamil intoxication and the improvement of survival (8/8 vs 3/6) is not significant.

Animals