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Biomedical subjects

G Petit

Publications and source records attributed to G Petit.

At least 19 recordsLinked to original sources
PubMed2000

Parasitology and immunology of mice vaccinated with irradiated Litomosoides sigmodontis larvae.

This study was performed with Litomosoides sigmodontis, the only filarial species which can develop from the infective larvae to the patent phase in immunocompetent laboratory BALB/c mice. Parasitological features and immune responses were analysed up to 3 months before and after challenge inoculation, by comparing 4 groups of mice: vaccinated challenged, challenged only, vaccinated only, and naive mice. Male larvae were very susceptible to irradiation and only female irradiated larvae survived in vivo. Protection, assessed by a lower recovery rate, was confirmed and was established within the first 2 days of challenge. This early reduction of the recovery rate in vaccinated challenged mice was determined by their immune status prior to the challenge inoculation. This was characterized by high specific IgM and IgG subclass (IgG1, IgG2a and IgG3) levels, high specific IL-5 secretion from spleen cells in vitro and a high density of eosinophils in the subcutaneous connective tissue. Six h after the challenge inoculation, most tissue eosinophils were degranulated in vaccinated challenged mice. Thus, in the protocol of vaccination described, protection appeared mainly to result from the stimulation of a Th2 type response and eosinophils seemed to be the main effectors for the increased killing of infective larvae in vaccinated challenged mice. Two months after challenge inoculation, the percentage of microfilaraemic mice was lower in vaccinated challenged mice as a consequence of this overall reduction in the worm load. In both vaccinated challenged and challenged only groups, the in vitro splenocyte proliferative capacity was reduced in microfilaraemic mice.

Animals↗
PubMed1998

[Acute poisoning during substitution therapy based on high-dosage buprenorphine. 29 clinical cases--20 fatal cases].

OBJECTIVES: Buprenorphine has been an important advance in care for drug abusers, but the toxic risk may be fatal. We report here two original series of buprenorphine poisoning in opiate abusers on substitution therapy. PATIENTS: The first series included 20 males and 9 females, aged 20-35 years (mean = 27.5) with non-fatal poisoning. The second series included 20 subjects (19 males, 1 female) aged 14-48 years (mean = 26.6) with a fatal outcome. All subjects were opiate addicts taking high-dosage sublingual buprenorphine formulation as substitution therapy. RESULTS: Blood concentrations of buprenorphine were found in all cases to remain at a low level (1.0-2.3 ng/ml, m = 1.4 ng/ml, and 1.1-29.0 ng/ml, m = 8.4 ng/ml in non-fatal and fatal cases respectively). Almost all cases involved concomitant intake of psychotropic medications, especially benzodiazepines (18 non-fatal and 17 fatal cases). DISCUSSION: These observations confirm previously reported data on the danger of buprenorphine-benzodiazepine combinations. Intravenous injection of crushed tablets also appears to be a risk factor (8 deaths and 10 non-fatal poisonings). This series highlights the need for improvement in the recently developed French program for substitution therapy with high-dosage buprenorphine in heroin addicts.

Administration, Sublingual↗
PubMed1998

Six deaths linked to concomitant use of buprenorphine and benzodiazepines.

AIMS: Buprenorphine at high dosage became available in 1996 for substitution treatment in France. This drug is considered particularly safe and has become widely available in general medical practice. We investigated the possible implication of a buprenorphine-benzodiazepine association in six deaths of known abusers. DESIGN: Full investigation of cause of death was conducted for six drug abusers. SETTING: The deaths occurred in two regions of France (Auvergne and Lorraine). Assays were carried out by the Institut de Medecine Legale at Strasbourg, France, one of the few French laboratories equipped to assay buprenorphine. MEASUREMENT: First, the blood and urine underwent triple exhaustive screening. Secondly, buprenorphine and norbuprenorphine were analysed in all the autopsy samples by HPLC/MS. FINDINGS: Benzodiazepine-buprenorphine associations were found in every case; no other substances that could account for the death were found. The tissue concentrations were markedly higher than the blood levels. CONCLUSION: If the number of deaths linked to such drug misuse proves high, it may be necessary to review how buprenorphine is dispensed.

Adolescent↗
PubMed1998

New features on the moults and morphogenesis of the human filaria Loa loa by using rodent hosts consequences.

The development of the human filaria Loa loa (Dirofilariinae, Onchocercidae), previously studied in monkeys, was studied using the non permissive hosts-mice and jirds. The development proved to be rapid: moult 3 occurred on day 8 post-inoculation, the adult stage was reached on day 25 and measured at that time 3-3.5 mm in length. As in the other filarioids, the female genital apparatus developed during the fourth stage. A critical analysis of the studies on the development of Onchocercid species was made. The optimal duration of the stages (i.g. the shortest time) was chosen for the comparison. It appeared that the duration of the stage 3 was a constant character in a given species whatever the experimental conditions, whereas moult 4 might be retarded in a non susceptible host. Comparison between the 18 developmental cycles of Onchocercidae in the vertebrate host was made. Two biological types could be distinguished: either the moult 3 occurred on day 2-3 and was followed apparently by a late moult 4 (> or = 50 days), or the moult 3 occurred after about one week of development and it was associated with a less long stage 4 (20-40 days). The first group includes Dirofilaria and Onchocerca, the second group brings together mainly Loa and the Onchocercinae of the Dipetalonema line and related genera (Acanthocheilonema, Brugia, Litomosoides, etc.). The groups thus formed suggest real relationships as they fit with the morphology of the infective stage and the results of a recent molecular analysis of the 5S DNA.

Animals↗
PubMed1997

Immune response to the filaria Litomosoides sigmodontis in susceptible and resistant mice.

Comparisons were made between the immune responses evoked during the course of chronic and patient infections of Litomosoides sigmodontis in susceptible BALB/c mice and non-patent infections in resistant B10.D2 mice. Early antigen specific responses of spleen cells were weak in both mouse strains. However, by day 58 post infection a strong Th2 response, as determined by production of IL-4, IL-5 and IL-10, was observed in BALB/c mice but not in B10.D2 mice. Antibody responses seemed to appear sooner in B10.D2 than in BALB/c mice, and these differentially recognised two antigens of 15 kD and 80 kD.

Animals↗
PubMed1997

Early reduction of the challenge recovery rate following immunization with irradiated infective larvae in a filaria mouse system.

The filaria Litomosoides sigmodontis, which develops a patent infection in BALB/c mice, was used to determine the fate of a challenge inoculum following immunization of mice with irradiation attenuated infective larvae (3 subcutaneous inoculations at weekly intervals with 25 L3 irradiated at 60 krad, and challenge with 25 L3 two weeks after the final immunization). The adult worm burden of vaccinated mice was reduced to 50% of that of controls although the pattern of larval migration and microfilaraemia were not affected. Necropsies showed that the increased killing of the filariae of the challenge inoculum occurred at the L3 stage within the first 2 days of challenge. This result draws attention on the protective mechanisms operating very early and probably in the subcutaneous region.

Animals↗
PubMed1997

Ivermectin and moxidectin in two filarial systems: resistance of Monanema martini; inhibition of Litomosoides sigmodontis insemination.

Effects of ivermectin and moxidectin were compared on two filarial species: Monanema martini which presents dermal microfilariae and induces Onchocerca-like lesions in its natural murid host Lemniscomys striatus, and Litomosoides sigmodontis (= L. carinii). M. martini microfilariae showed an unusual resistance to ivermectin, in vitro and in vivo; moxidectin was no more efficient. However, the two drugs used at high concentrations deeply altered the uterine embryogenesis, but had no lethal effect on adult filariae. L. sigmodontis blood microfilariae showed a great susceptibility to moxidectin, similar to that previously described for ivermectin. The two drugs also induced a long term effect because they inhibited the insemination of the female filariae. This result reinforces the observations made by other authors on the human parasite, Onchocerca volvulus.

Animals↗
PubMed1996

Rapid delineation of closely-related filarial parasites using genetic markers in spacer rDNA.

Two closely-related species of filarial parasite, Litomosoides galizai and L. sigmodontis, were characterised using a polymerase chain reaction-linked restriction fragment length polymorphism (PCR-RFLP) technique. The rDNA region spanning the first and second internal transcribed spacers as well as the 5.8S gene (ITS+) was amplified by PCR from each of the species using conserved primers to the 18S and 28S ribosomal genes, digested separately with a range of restriction endonucleases and the fragments separated by agarose gel electrophoresis. PCR-RFLP of ITS+ using endonucleases Alu I, Cfo I, Dra I, Rsa I and Vsp I produced characteristic patterns for each species. No variation in RFLP patterns was detected among different DNA sample preparations or the sexes of each species. The present study demonstrates that the ITS+ provides genetic markers for the differentiation of L. galizai from L sigmodontis and suggests that internal transcribed spacer rDNA may provide species markers for other filarioid nematodes. Such markers have implications for diagnosis and for studying the biology, pathogenesis and systematics of filarial parasites.

Animals↗
PubMed1996

The fate of the filaria Litomosoides sigmodontis in susceptible and naturally resistant mice.

The fate of Litomosoides sigmodontis was compared in susceptible BALB/c and resistant B10D2 mice, presenting the same major histocompatibility complex (H-2d), with an attempt to dissociate the different elements of the life cycle in order, later, to dissociate the different mechanisms involved. Each female mouse was inoculated once with a small dose of infective larvae (25 L3) or a large dose (100 or 200 L3). In total, 92 BALB/c and 49 B10D2 were studied. Necropsies were performed up to D85 following infection with 25 larvae. The early fate was similar in B10D2 and BALB/c mice; particularly the recovery rate of worms was almost identical during the first month p.i. and represented a quarter of the inoculated larvae. Resistance in B10D2 mice appeared progressively, as judged by retardation of growth and of the fourth moulting, the presence of very small sterile female worms and male worms with abnormal left spicule, and a high frequency of live filariae coated with inflammatory cells and encapsulated dead worms. The L. sigmodontis life span in B10D2 was about half that in BALB/c. Necropsies were carried out up to D20 following infection with 100-200 L3. The recovery rate was increased in BALB/c. Growth was retarded earlier in B10D2 mice, this crowding effect already apparent at D10; this may indicate a role for metabolic factors. The pattern of the life cycle in both mouse strains confirms recent conclusions on Onchocercinae: the recovery rate is established as soon as the second day during "phase 1 of massive destruction", then it is stable during "phase 2 of insignificant mortality". During phase 1, the infective larvae are immediately destroyed in the subcutaneous tissue if they are not able to escape the inflammatory process by penetrating in local lymphatic vessels. By contrast, phase 2, which is longer than the duration of the third larval stage, indicates there is no mortality linked to the third moulting, at least following a single inoculation.

Animals↗
PubMed1995

[Left ventricular thrombosis complicating systemic lupus erythematosus].

The authors report an isolated pediculated thrombus in the left ventricle of a young 14 year old girl with systemic lupus erythematosus with antiphospholipid antibodies without any other cardiovascular abnormality, especially ventricular wall motion abnormalities. After surgical ablation of the thrombus, the patient was followed up to avoid recurrence. This type of cardiac lesion (ventricular thrombosis without underlying myocardial disease) is exceptionally rare. Echocardiographic follow-up after surgical ablation showed no recurrence of thrombosis after four years.

Adolescent↗
PubMed1994

An unusual death by zipeprol overdose.

Capillary gas chromatography coupled to mass spectrometry was employed to quantify zipeprol in biological fluids and tissues in a death attributed to oral zipeprol ingestion. The blood concentration of zipeprol was 6.69 mg/l. Hair analysis clearly indicated chronic drug abuse, with a concentration of 33.1 ng/mg. Results are discussed in the light of the existing literature.

Adult↗
PubMed1994

Larval biology of six filariae of the sub-family Onchocercinae in a vertebrate host.

The development of six filariae of the sub-family Onchocercinae-Litomosoides sigmodontis, Acanthocheilonema viteae, Molinema dessetae, Monanema martini, Brugia malayi, B. pahangi-was compared in rodents, following a single inoculation of a low or high dose of infective larvae. Analysis was done with 105 rodents dissected and 53 rodents fixed for histopathology. The percentage of larvae which developed corresponded to the proportion of those which were able to penetrate into the sub-cutaneous lymphatic vessels; this percentage was determined during the first day (phase 1) and was characteristic of the filaria-host pair, and independent of the number of larvae inoculated. It could remain stable for a long time, more than eight months with M. martini (phase 2); the phenomena of regulation appeared later (phase 3). The larvae migrated through the lymphatic system, which represents a medium less protected and thus less aggressive than the blood system. The coelomic cavities, almost devoid of inflammatory cells, represented an ultimate shelter, as well as the joint-cavities (colonized by some Dirofilariinae). Localizations in the cardio-pulmonary blood system were accidental and occurred when, during the migrations, some larvae penetrated into the thoracic channel and arrived in the superior vena cava, then the right ventricle and the pulmonary arteries (the biology of Dirofilaria immitis resulted in a secondary adaptation); such accidents may occur with adult filariae, especially, after drug treatment. One may expect similar events in human filariasis. These "occult" filariae, more frequent than it is usually thought, influence the immunological status and the pathology.

Animals↗
PubMed1994

Monanema martini in its murid hosts: microfiladermia related to infective larvae and adult filariae.

The microfiladermia of Monanema martini was studied in two natural murid hosts, Lemniscomys striatus and Arvicanthis niloticus, with 137 and 39 rodents respectively inoculated once, twice or several times. Microfilarial densities (mf/mm2) were measured at the ear pinna every three months. Almost all the rodents developed a microfiladermia. When L. striatus rodents were inoculated once with 30, 80, or 400 infective larvae, microfiladermia increased (peaks of 108, 148, 174 mf/mm2 respectively, at six to nine months p.i.); this fits with the fact that, in this filaria-host pair, the number of adult filariae is proportional to the number of inoculated larvae, and remains at a constant level for more than eight months. Nevertheless microfiladermia was limited, especially during the peak, showing the complexity of its regulatory mechanisms. Several low doses over one year, resulting in 145 L3, increased the microfiladermia at the same level than one dose of 400 larvae; the recovery rate of the larvae was reduced but the total number of filariae recovered was increased. A. niloticus, from which the filarial strain originates, showed a much lower microfiladermia than L. striatus (7 mf/mm2 with 80 larvae, at six months p.i.). This was due to a smaller recovery rate of the infective larvae in this host and, overall, to a reduced fertility of the female worms and a shorter lifetime of adult filariae. However, repeated inoculations increased the microfiladermia (32 mf/mm2), due to the constant presence of small numbers of young filariae producing microfilariae. It is to be noted that the two biological systems presented by M. martini in L. striatus and A. niloticus correspond to the two types of ocular pathology described in a recent opthalmological study, chorioretinal atrophy and keratitis respectively.

Animals↗
PubMed1993

Is disease progression the major factor in morphine 'tolerance' in cancer pain treatment?

To assess the contribution of pharmacological tolerance to increasing doses of morphine, 29 cancer patients requiring oral morphine to treat pain were studied by two teams working independently. The first team assessed physical impairment, pain intensity and pain treatment. The second team assessed depressive disorders (DSM III criteria), emotional and behavioural depressive patterns (Retardation Depressive Scale, Polydimensional Mood Scale). All patients were seen at the initiation of morphine therapy and followed to the first morphine dose modification. Evaluations were carried out in out-patient clinics except staging investigations which were undertaken at the beginning and at the end of the study. Our results showed that (1) in 24 of the 25 patients for whom morphine doses were increased, progressive disease was recorded; (2) in 4 patients, morphine doses were not increased and in these patients their disease was stable or in remission; and (3) changes in depressed mood were not correlated with pain intensity. These data strongly suggest that, instead of pharmacological tolerance, the main factor resulting in increasing oral morphine requirement in cancer pain management is pain increase due to disease progression.

Adult↗
PubMed1993

Effect of ivermectin on two filaria-vector pairs. Brugia malayi-Aedes aegypti; Litomosoides sigmodontis-Bdellonyssus bacoti.

The effect of ivermectin was studied on two filaria-vector pairs, Brugia malayi-Aedes aegypti and Litomosoides sigmodontis-Bdellonyssus bacoti. The rodent hosts, respectively Mastomys coucha and Meriones unguiculatus, were treated with ivermectin doses of 0.05 mg/kg, or 0.2 mg/kg or 2 mg/kg. Batches of vectors were fed on rodents, infected or not, treated or not, from H7 to D43 post-ivermectin. Vector survival was observed and dissections were performed to study the filarial development. It appears that ivermectin has no systemic effect on vectors, or very little. The drug acts on transmission because it affects the microfilariae. Transmission of L. sigmodontis is blocked because microfilariae are eliminated from the blood. Transmission of B. malayi is blocked although microfilaremia remains present at a low level. Two particular features are observed: microfilariae are hyper-ingested, but they do not cross the stomach wall (in contrast, they cross at a high rate in the control batch of Aedes, due to the "stomach wall limitation"). These events might be explained by a muscular passivity of the microfilariae treated with ivermectin. Transmission of the two filarioid species is restored normally about D25-40 post ivermectin because a new population of microfilariae has appeared. These ivermectin experiments emphasize the diversity and complexity of two important phases of the filarial cycle in the vector: the ingestion of microfilariae and the passage through the stomach wall.

Aedes↗
PubMed1993

Ophthalmological study of the lesions induced by the filarial worm with dermal microfilariae, Monanema martini, in its murid hosts.

The filaria Monanema martini with skin-dwelling microfilariae induces in its natural murid hosts lesions similar to those in human onchocerciasis. This was demonstrated by histo-pathological studies but it appeared useful to evaluate the model by a clinical investigation. An ophthalmological analysis was performed on the two species of hosts, inoculated by one, two, or multiple doses of larvae, and with infections of at least one year duration. A total of 140 eyes was examined (anterior and posterior segments). We established a system for enumerating the different types and severities of lesions. We prepared a file for each eye and attempted to quantify our observations. The significant lesions were different in the two host species. In Arvicanthis niloticus, in which motile microfilariae were seen in the anterior segment, punctate keratitis was predominant. In Lemniscomys striatus, the posterior segment showed complete chorioretinal atrophy, similar to the final stage of onchocercal chorioretinitis in humans. M. martini represents in its natural hosts two complementary models for the study of the pathogenesis and treatment of human onchocerciasis.

Animals↗