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Biomedical subjects

J A Nicolas

Publications and source records attributed to J A Nicolas.

At least 19 recordsLinked to original sources

An interactive tool to visualize three-dimensional ultrasound data.

Three-dimensional ultrasound can provide images that are easily understood by people who are not specialists in ultrasonography. However, current visualization methods do not perform very well on 3-D ultrasound data. Apart from some specific cases (obstetrics, cardiology), 3-D ultrasound images have not yet demonstrated major benefits from a clinical point of view. In this article, we introduce an interactive method that allows the user easily to produce 3-D images for each ultrasound examination. It is a two-step method. First, the user roughly segments the data by drawing three boundary curves in perpendicular planes. A ray-casting algorithm then automatically retrieves the details of the objects. Because it can be used routinely, this tool should help to evaluate the potential of 3-D ultrasonography.

Algorithms↗

Copper and zinc exposure of zebrafish, Brachydanio rerio (Hamilton-Buchaman): effects in experimental Listeria infection.

To investigate the effects of heavy metals on susceptibility of fish to Listeriosis, normal zebrafish, Brachydanio rerio (Hamilton-Buchanan), were exposed to varying concentrations of zinc (0.05, 0.15, and 0.25 mg/liter) and copper (0.05, 0.10, and 0.15 mg/liter). During copper exposure, this heavy metal did not accumulate in zebrafish kidney. Unlike copper, a small amount of zinc accumulated in kidneys of fish exposed at 0.25 mg/liter. To estimate the effects of this heavy metal on listerial infection, the mortality of fish and the number of viable bacteria in fish kidney were determined at various times (1, 4, 7, and 10 days) after ip challenge with Listeria monocytogenes (strain 31386, serotype 4b). The results indicate that the number of colony-forming units in zinc-exposed fish decreased at 4, 7, and 10 days after challenge with 0.2 x LD50 of viable bacteria. In contrast, copper-exposed fish indicated both decreases and increases in the number of colony-forming units depending on the concentration of L. monocytogenes used.

Adjuvants, Immunologic↗

Trypanosoma brucei brucei: antitrypanosomal evaluation of stilbamidinium hexachloroiridiate on the murine CNS model and iridium serum kinetics in infected sheep.

Stilbamidinium hexachloroiridiate was found trypanocidal in vitro against Trypanosoma brucei brucei IPP at 600 microM after a 1 h incubation period and 30 microM after 24 h. This activity was confirmed in mice with a subcutaneous treatment at 20 mg/kg in a single dose. It was then evaluated on T.b. brucei murine CNS model. At the early stage, a subcutaneous treatment at 2 mg/kg/day x 5 cured 50% mice where-as one single dose at 10 mg/kg was completely inactive. Higher doses failed to cure the mice. Nevertheless, hexachloroiridiate salt of stilbamidine was 3.3 fold less toxic than dihydrochloride salt. Although the compound appeared inactive at the late stage of the murine trypanosomiasis, the difference of toxicity justified its evaluation on the early stage of sheep trypanosomiasis. The compound was trypanocidal at 2 mg/kg in a single dose when administered 8 days after infection. The study of iridium serum kinetic showed that stilbamidinium hexachloroiridiate was distributed rapidly according to a monocompartmental model. Moreover, iridium persisted in serum for a long time. The compound in aqueous suspension with 1% carboxymethylcellulose acted therefore as a controlled release system with a bioavailability allowing its trypanocidal action at the early stage.

Animals↗

[Virulence of Listeria monocytogenes in pregnant mice].

Serious food-borne outbreaks of listeriosis have been reported in North America and in Europe, during the past decade. The predominant risk groups appear to be immunocompromised adults, elderly people, newborn babies and pregnant women. In order to examine the relationship between alimentation, listeriosis and pregnant females, we developed an experimental model using Swiss mice fed ad libitum during 4 days with pellets containing a high concentration of Listeria monocytogenes serovar 4b (10(9) u.f.c/g). Samples were taken from many series of pregnant mice which had been infected respectively by L. monocytogenes from 6th, 10th, 14th and 18th day of pregnancy onwards. This was compared to non infected control series. The transmission of infection from mother to progeny and contamination of surviving progeny were evaluated by Listeria numeration in liver, brain and intestines. Females infected between day 6 and day 10, and between day 10 and day 14 after fertilization, aborted or died of encephalitis. Mice contaminated between day 14 and day 18, were the least prone to experimental listeriosis. On the other hand, some mice contaminated between day 18 and day 22, i.e. at the end of their pregnancy, may develop encephalitis a few days after parturition of a healthy litter. Series contaminated between day 6 and day 10, and between day 10 and day 14 turned out to be highly sensitive to the transmission of infection from mother to young. In two other series (day 14--day 18; day 18--day 22), the young mice contained generally no Listeria. Our experimental model shows the relationship between listeriosis and alimentation. In pregnant mice, sensitivity to infection depends on their gestational status with large individual variability.

Adult↗

Trypanocidal activity and platinum plasma kinetics of cis-Pt pentamidine iodide in Trypanosoma brucei sheep model.

The trypanocidal properties of cis-Pt pentamidine iodide have been studied on the T. b. brucei sheep model. The compound was evaluated on the lymphatic-plasma phase of the disease and appeared to be active on the circulating parasites. Cis-Pt pentamidine iodide was active at 5 mgl.kg-1 in one single dose both in mouse and sheep trypanosomiasis models. The chemotherapeutic index was about 200 in the mouse. As we observed previously with the chloride derivative, platinum plasma values for cis-Pt pentamidine iodide were rather constant between 24 and 48 hours. The nature of the salt associated to cis-Pt pentamidine had a direct effect on the compound kinetics. The iodide compound was distributed quickly and largely within deep compartments according to a monocompartmental model. The theoretical volume of distribution was 6.41.kg-1 for a 100% absorbed fraction. The two iodide ions of the complex probably played an important role in the compound kinetics mainly due to the extended release effect. The iodide salt of cis-Pt pentamidine could therefore be used in chemoprophylaxis of African trypanosomiasis.

Animals↗

Human African trypanosomiasis: presence of antibodies to galactocerebrosides.

Improvements were made in the immunodetection of anti-galactocerebroside (anti-GalC) antibody in sera of patients with human African trypanosomiasis by thin-layer chromatography, enzyme-linked immunosorbent assay, and immunoadsorption. Rabbit anti-GalC antibodies were used to standardize these techniques and demonstrate their specificity. Anti-GalC antibodies were found in the sera of 42.8% of 63 patients with human African trypanosomiasis. Thirty-four control subjects living in the same endemic area were also tested. Anti-GalC levels were higher in human African trypanosomiasis patients with neurologic disturbances compared with patients without such disturbances. These antibodies were distributed mainly between the IgG and IgM classes, but 28% of the patients with human African trypanosomiasis had increased IgA levels without anti-GalC antibody activity.

Agglutination Tests↗

Procedural skills of practicing gastroenterologists. A national survey of 700 members of the American College of Physicians.

OBJECTIVE: To find which procedures gastroenterologists do in their practice, where they learned the procedures, and what training they recommend to achieve and maintain competence in each. DESIGN: Mailed survey. PARTICIPANTS: A random sample of 700 gastroenterologists who were members of the American College of Physicians, of whom 510 (73%) responded. RESULTS: Gastroenterologists did a median of 27 of the 40 gastroenterology procedures and 3 of the 16 general medicine procedures. A larger number of different procedures was done by those who were board certified in gastroenterology, spent more than 60 hours per week in patient care, graduated after 1969, or practiced in a university setting, a hospital with 250 to 500 beds, or a group limited to gastroenterologists. The majority of respondents had done each of the three most commonly done procedures 200 or more times in the previous year. For 10 procedures studied in detail, the majority had done 9 of the 10 in the past year at least as often as the median recommendation for maintaining competence. The number of procedures recommended to achieve and maintain competence differed little by the age, type of practice, and gastroenterology board certification status of the respondent. For most procedures, the range of recommendations was broad, but the median numbers agreed with other published recommendations. Respondents learned 31% of procedures after they had completed training. The earlier their training, the more likely they had learned the procedure in practice. CONCLUSIONS: Gastroenterologists do many different procedures, and this number is influenced by how recently they were trained and the nature of their practice. Respondents learned nearly one third of the procedures they do after they had completed training. It is an important and continuing challenge for the profession to assure that physicians learn and maintain these procedural skills at the highest level of proficiency.

Clinical Competence↗

Procedural skills of practicing nephrologists. A national survey of 700 members of the American College of Physicians.

OBJECTIVE: To determine which procedures nephrologists do in practice, where they learned the procedures, and how much training they recommend to achieve and maintain clinical competence in each. DESIGN: Mailed survey. PARTICIPANTS: A random sample of 700 members of the American College of Physicians who were identified as practicing nephrologists; 516 (74%) responded. RESULTS: Acute peritoneal dialysis, acute hemodialysis, continuous arteriovenous hemofiltration, and percutaneous renal biopsy were done by 95%, 97%, 87%, and 91% of the respondents, respectively. Except for hemofiltration, procedures were learned by most respondents during fellowship training. Compared with general internists, fewer nephrologists did most of the 19 general procedures included in the survey. The number of nephrology procedures done during the past year varied considerably among respondents, as did the minimum number of procedures they recommended for achieving and maintaining competence. Neither the variation in number of procedures done nor recommendations regarding certification were explained by differences in practice characteristics. Median recommendations remained relatively constant among subgroups. CONCLUSIONS: Nearly all nephrologists do the four nephrology procedures included in the survey. Their opinions about the training needed for competence help to better define requirements for training programs. More attention should be focused on training and certifying practicing nephrologists in procedures learned after formal fellowship training.

Biopsy, Needle↗

[Plasma kinetics of a spiroarsorane trypanocidal agent in sheep trypanosomiasis].

In a previous study, spiroarsoranes were very effective against both the two pathogenic phases of the experimental sheep trypanosomiasis. In this paper, the authors had studied the plasmatic pharmacokinetics of these compounds. Data had shown one peak 10 min after injection of a 3 months inoculated sheep, and 90 min for the control sheep. Spiroarsorane had a good diffusion into the central nervous system, but the trypanocidal activity, during the second phase of the disease, was effective only after repeated treatment. The spiroarsorane low toxicity could allow its direction against nervous trypanosomiasis.

Animals↗

[Trypanocidal activity and plasma kinetics of cis-Pt(II) pentamidine in the parasitized sheep].

The trypanocidal activity of cis-Pt(II) pentamidine had been demonstrated during the first phase of Trypanosoma brucei brucei sheep experimental trypanosomiasis. But a subcutaneous treatment with 5 mg.kg-1 (+2 x 12 mg.kg-1) was not effective during the brain phase of trypanosomiasis. The blood pharmacokinetics of this compound had a plasmatic peak between 45 and 60 min, followed by a low decreasing phase along several days. The curve shape allowed an important interval before the following injection, and showed a compound storage in internal organs and extravascular sites. A model of cis-Pt(II) pentamidine metabolism had been studied: this product could be used as a chemoprophylactic medicine against African trypanosomiasis and American leishmaniasis.

Animals↗

Procedural skills of the general internist. A survey of 2500 physicians.

STUDY OBJECTIVE: To determine which of 40 clinical procedures general internists do in their practice, how often these procedures are done, and what training is needed to develop and maintain competence in each. DESIGN: Mailed survey. PARTICIPANTS: A random sample of 2500 American College of Physicians (ACP) members identified as general internists; 1806 (72%) responded. Of these, we excluded 398 who were board eligible or board certified in a subspecialty and 143 with unknown status. The resulting sample of 1179 was augmented in selected analyses by an additional sample of 199 rural internists. RESULTS: General internists did, on average, 16 of the 40 procedures. Practice characteristics markedly affected the number and variety of procedures done. A larger number of different procedures was independently associated with smaller cities, smaller hospitals, younger age, increased hours in patient care, and certain regions of the country. Practice characteristics varied considerably by practice type and location. Many procedures were done infrequently. There was reasonable agreement on the experience needed to attain and maintain competency in each procedure. The majority of respondents favored hospital credentialing for 22 of the 40 procedures. CONCLUSIONS: General internists do a wide variety of procedures, the number and frequency of which are affected by the characteristics and location of their practice. Despite opinion to the contrary, more recently trained general internists do a wider variety of procedures than older colleagues. These results provide data to help define standards for training and credentialing and suggest that we should reexamine general internists' training in procedural skills.

Attitude of Health Personnel↗

Procedural skills training in internal medicine residencies. A survey of program directors.

STUDY OBJECTIVE: To obtain the opinions of internal medicine residency program directors about which procedural skills residents master during training and the amount of training needed to attain and maintain competence in each procedure. DESIGN: A mailed survey to all program directors in the United States. RESPONDENTS: Program directors or their designees from 389 of 431 (90%) internal medicine residency programs. RESULTS: For several procedures, 40% more respondents said all residents should master the procedure than said all their residents do master the procedure. Some procedures commonly done in practice were perceived as mastered by all residents in fewer than half of the programs. There were few differences in procedures learned by size or type of program. A fellowship program did affect exposure to some procedures in the field covered by the program. Median recommendations of training needed to master each procedure were similar to those of practicing internists for most procedures. CONCLUSIONS: Current residency training does not assure competency in all of the procedures the general internist does in practice. Program directors should examine which skills are adequately taught, test competence, and ways to improve residents' skills. Practicing general internists should have access to supervised training in procedural skills.

Clinical Competence↗

Isolation of Listeria from French meat products.

One hundred and ten Listeria strains were recovered from 378 meat samples: L. monocytogenes (68 strains), L. innocua (45) and L. welshimeri (7). L. monocytogenes isolates mainly belonged to serogroup 1/2 (1/2: 23 strains; 1/2b: 1; 1/2c: 43; 4b: 1). These results contrast those observed for 355 human strains isolated during the same period in France where serovar 4b strains were largely predominant (66.5%). 45% of the strains were phage typable. These results underline the widespread occurrence of Listeria in meat products.

Animals↗

[Detection of visna-maedi virus antibodies and antigens by immunoblotting].

The visna-maedi virus was immunologically diagnosed using an immunoblotting technique from an antigenic preparation of the visna-maedi virus K796 purified by sucrose density gradient centrifugation. After SDS-PAGE electrophoresis and transfer onto a nitrocellulose sheet, the immunoblotting procedure was adapted to the search for specific antibodies in ovine serum samples. The results obtained showed that, in the natural visna-maedi disease, antibodies are not systematically detectable against every viral protein of the virus core. We have demonstrated the existence of antibodies directed against the proteins coded by the gag and the pol genes.

Animals↗

[Early auditory evoked potentials in normal sheep and in sheep with trypanosomiasis].

In human and animal clinics, the early auditory potential has been used for a long time in the detection of lesions through the internal auditory way in the cerebral trunk. The aim of this work tries to determine if this non invasive test is apt to show up and to follow the evolution of lesions at the level of auditory way in the cerebral trunk of sheep with trypanosomiasis. According to the human technic, the list of the early auditory potential was realized against ten healthy sheep and ten sheep with trypanosomiasis (Trypanosoma brucei brucei) at the nervous phase. No significant anomalies exist in the sheep with trypanosomiasis. The results are discussed.

Animals↗

[Treatment of experimental trypanosomiasis caused by Trypanosoma brucei brucei in sheep: study of the minimum active dose of melarsoprol].

Trypanosoma brucei brucei experimentally infected sheep with central nervous system involvement were treated with melarsoprol (Arsobal, Specia, France). The purpose was to determine minimum efficiency concentrations of this drug. Eight sheep divided in four groups of two animals were treated intravenously for 3 days with the following respective dosages: 1.8, 0.9, 0.45 and 0.225 mg/kg/d. After a year of observation, efficient dosages were 1.8 and 0.9 mg/kg/d. The experimentation suggests the possibility to reduce usually given dosages in man.

Animals↗

[A new series of antiparasitic organic arsenicals: the spiroarsoranes. Experimental trypanocidal activity].

Arsenical compounds are the main therapeutic way, effective in the neurological phase of trypanosomiasis. Unfortunately, their important toxicity prevents their easy administration. Structural cyclization of arsonic acid derivatives has led to a class of non-toxic compounds: spiroarsoranes. A 47 compound primary screening on an in vivo murine model of Trypanosoma brucei brucei resulted in the isolation of a very effective derivative after a single subcutaneous injection of 30 mg.kg-1 body weight (Chemotherapeutic Index = 21). In this study, trypanocidal activity of this compound was evaluated on an in vivo sheep model of trypanosomiasis by T. brucei brucei, according to experimental model of the Institute of Neurological Epidemiology and Tropical Neurology of Limoges (France). A single subcutaneous injection of 30 and 100 mg.kg-1 b.w., and 30 and 60 mg.kg-1 b.w. was given respectively during first and second phase of trypanosomiasis. Ovine pharmacokinetics of this compound will be evaluated in a further study.

Animals↗

[Treatment of experimental trypanosomiasis of sheep caused by Trypanosoma brucei brucei: efficacy of Ro 15-0216 (a 2-nitroimidazole derivative)].

An experiment was carried out on treatment of Trypanosoma brucei brucei experimentally infected sheep with central nervous system involvement with a 2-nitroimidazole derivative: Ro 15-0216 (Hoffmann La Roche & Co Ltd, Basel, Switzerland). After a single intramuscularly or intravenously administration (25 or 50 mg/kg) of this compound in healthy sheep, levels of more than 1 microgram/ml corresponding to trypanocidal concentrations are detected in both blood and cerebrospinal fluid. However, because of short half life, two or three injections a day appeared to be necessary. Six infected sheep were treated by daily intravenous injection for six days: three animals with 25 mg/kg/d and three others with 50 mg/kg/d. Animals which relapsed received 50 mg/kg/d divided in three intravenous injections a day for six days. After a year of observation, all the animals were considered clinically and biologically cured.

Acetanilides↗