Biomedical subjects
Publications and source records attributed to G Petit.
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.
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.
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.
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.
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.
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.
When inoculated subcutaneously, the infective larvae of L. sigmodontis undergo complete development and produce a patent microfilaraemia in mice of the BALB background (BALB/c, BALB/K and BALB/B, with respectively the H-2d, H-2k et H-2b haplotypes). The most susceptible strain is BALB/c with all mice harbouring adult filariae and 47% of mice presenting with a patent microfilaraemia. Mice with the B10 background (B10, B10Br and B10D2, with respectively the H-2b, H-2k et H-2d haplotypes) are almost completely resistant to infection. Adult filariae were recovered from all mice of the CBA/Ca, CBA/HN, C3H/HeN, DBA/2N strains. However, the site and structural development of the parasite varied in each strain. Absence of microfilaraemia is associated with absent or abnormal spicules, reduced number of female filariae and small size of female filariae. These results show that the Major Histocompatibility Complex only modulates the developmental pattern of filariae within the limits imposed by background genes. Male CBA/HN and C3H/HeN were more susceptible to infection than female mice. Inverse phenomenon was observed with strains BALB/c; and, no host sex effect was seen in DBA/D2N.
The mites, Bdellonyssus bacoti, are engorged on rodents having 800 to 60,000 microfilarie/10 mm3 blood. Quantitation of L. galizai larval development shows that an additional blood meal improves development and that high microfilaremiae do not result in a proportional increase in the number of infective larvae. The first important stage of transmission regulation occurs during ingestion of microfilariae: the numbers of ingested microfilariae are lower than expected in cases of high microfilaremia. This phenomenon cannot be ascribed to the mite vector that engorges a constant blood meal whatever the level of microfilaremia. Contrarily, one finds that microfilarial density in the small peripheral blood vessels (blood drawn from incision of the dorsal skin) increases less than in large blood vessels (retro-orbital sinus). A similar observation was reported by Dickerson et al. (1989) working with Wuchereria bancrofti. We assume that in both cases, the high microfilaremiae cause the small blood vessles accessible to the vector to become saturated with parasites. Although regulation during engorging is not the sole factor to monitor the infection in B. bacoti (another one operates during larval development of L. galizai), demonstrating its existence seems to us fundamental: it points out the concept that sub-ingestion, as well as over-ingestion, shows the inequalities of microfilarial densities in the host which seem to be dependent on mechanical factors such as the diameter of blood vessles and the size of microfilariae.
Screening for human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) antibodies was carried out in the serum of 1,245 leprous patients and 5,731 controls selected in nine different centers from the Congo, Ivory Coast, Senegal, and Yemen Arab Republic. In Yemen, all sera were negative. In the Congo, the seropositivity among patients and controls was, respectively, 3.8 and 5.2%; in Senegal, it was 1.3 and 0.6%; and in the Ivory Coast 4.8 and 3.9%. Differences were not statistically significant, even considering lepromatous or tuberculoid forms (3.6% and 3.7%, respectively). HIV-2 antibodies were only detected in subjects from the Ivory Coast and Senegal. Using appropriate criteria for seropositivity (confirmation by Western blot, reactivity to HIV envelope glycoproteins) and a large selection of patients (several countries with several centers), it appears that leprosy (and specially the lepromatous form) is not a factor for HIV infection.
A redescription of the type specimens of the three following species is given: L carinii (Travassos, 1919) from Sciurus sp. in Brazil. L, sigmodontis Chandler, 1931 from Sigmodon hispidus and L. scotti Forrester et Kinsella. 1977 from Oryzomys palustris in North America. A description of two brazilian species is also given: L. galizai n. sp. from (Ecomys trinitatus tapajinus and L. kohnae n. sp. from Nectomys squamipes. The conclusions are: The type species of the genus Litomosoides: L. sigmodontis, and L.carinii are two distinct species. As a result, the filaria which is widely used in drug trials has to be reinstated sigmodontis and not curinii. With the exception of the two parasite species of Geomyid rodents, which show affinities with the genus Litomosa, the species of Litomosoides may be devided into two groups, principally based on the morphology of the spicules: the sigmodontis group, with 13 species; the carinii group, with 8 species. Each group includes parasites of Chiuroptera, Marsupials and Rodents. The two new species (L. galizai and L. kohnae) belong to the group sigmodontis; they are characterised by the shape of the buccal capsule, the size of the spicules, the structure of the female body-wall and the microeilaria.
L. galizai develops in the gamasid B. bacoti in 11 days at 28 degrees C. Molts I and II take place respectively 5 and 7 days after feeding. The development is studied in the adult female mites; as for the laboratory filaria L. sigmodontis, the interstitial tissue is the main parasitized organ; microfilariae penetrate in the two cell types which constitute it: adipose cells and secretory cells (these secretory cells are described here for the first time). The filariae develop also in the salivary glands, the digestive wall, the genital envelopes and exceptionally in the coxal and vaginal glands. The filariae produce the formation of syncytia. Larvae which stay in the haemocele do not develop.
The widespread use of man-made mineral fibres (MMMF) as insulation products in buildings can be a potential source of indoor pollution, but few data are available. Pollution levels were determined at 79 indoor and 18 outdoor locations. The standardized method (membrane filter method) was adapted to the environmental settings: 10 m3 of air was sampled over a period of 5 days; the specimen was prepared by an indirect method (low-temperature ashing); counting was carried out at a magnification of 250; MMMF were identified by their optical properties under the polarizing optical microscope. Indoor pollution levels were found to be in the range 0-6230 respirable fibres per m3, with a median value of 3. Outdoor airborne pollution levels were lower than 15 respirable fibres per m3, with a median value of 1. More data are needed in order to make a more precise assessment of the risk associated with environmental MMMF pollution; a standardized method of obtaining such data is also necessary.
The objective of the present study was to evaluate serum alkaline DNase activity (SADA) variations as a useful means of lung cancer monitoring therapy. SADA was measured in 40 patients with non-small cell and small cell carcinomas. Blood samples were collected before (Time 0), during the treatment and months after therapy. A decrease in SADA during the first treatment indicates a good clinical response, whereas an absence of decrease indicates a non-response to treatment. In patients who respond to therapy, three types of variations of SADA are observed during the clinical course. A progressive regaining of SADA up to a value largely exceeding the level of the initial SADA value (T0) correlates with a complete remission. An incomplete regaining of enzyme activity corresponds to a partial remission, whereas no regaining of SADA precedes a fatal evolution. Such variations in SADA observed in the 40 patients with lung carcinomas support our previously published clinical results, confirming that the variations of SADA could be a reliable marker for the therapeutic monitoring of different human malignancies.
Morphological and histological analysis of the larval development of Monanema martini, a filaria with skin dwelling microfilariae. The vectors are the hexapod larvae of Rhipicephalus sanguineus, R. turanicus and H. truncatum; the filarial infective stages appear during the larval-nymph moult of the vector (11 days at 26 degrees C). This species, and in our opinion the other species of Monanema, have a complete development in the epidermis of the ticks. Hard-ticks (Ixodidae) appear to be the main vectors of filariae with skin-dwelling microfilariae belonging to Dipetalonema evolutionary line: Yatesia, Cherylia, Cercopithifiliaria, Monanema.
Histological and ultrastructural analysis of the development of C. roussilhoni--a filarial parasite of A. africanus with skin-dwelling microfilariae--in the hexapod, larva of R. sanguineus. The development takes place in the epidermis. The intra-epidermal development, which is rare in the Spirurida, is known in a close filaria, also transmitted by Ixodids, Monanema martini. The slow development of C. roussilhoni and the pronounced changes of the parasitized epidermal syncytium (very large nuclei; expanding nuclear envelop and cellular membrane which form complicated expansions; many dilatations of the endoplasmic reticulum) demonstrate the more primitive state of this filaria.
A comparative study was made of skin biopsies from onchocerciasis patients living in the forest and in the savanna of West Africa. The lesions and their pathogenesis were similar in the two series of patients. An inflammatory reaction around the extra-lymphatic microfilariae was observed. But the localization of the microfilariae was slightly different: the mean distances between the microfilariae and the border of the basement membrane of the epidermis was approximately 115 microns in the forest and 138 microns in the savanna. Statistical analysis showed that the forest microfilariae were in the superficial parts of the dermis when the densities were low and in deep parts of the dermis when the densities were high. In the savanna, the phenomenon, although less clearly defined was reverse. The two situations were inverted when the density of microfilariae reached approximately 51 microfilariae per calibrated snip, which was seldom the case. Therefore, the most cases, microfilariae appeared to have been more superficial in the forest than the savanna.
A single dose of DEC was given to Lemniscomys striatus parasitized by Monanema martini. The histopathological analysis of ear-lobe skin sections shows: a massive escape of microfilariae from the lymph capillaries, a major vascular exudative reaction with edema and diapedesis of blood cells. This inflammatory process leads to the destruction of the extralymphatic microfilariae and it induces a subacute and chronic dermatitis at the 7th day. These findings explain the pathogenesis of Mazzotti reaction during treatment of human onchocerciasis. The use of DEC produces precisely the factor that is responsible for the severity of the human disease: inflammatory reactions around the extralymphatic microfilariae.
Skin and ocular lesions were studied in murids Lemniscomys striatus L. infested by 2 isolates of Monanema spp, a rodent filaria with skin-dwelling microfilariae. Histologic examination disclosed microfilariae in lymphatic vessels. Penetration of microfilariae in extra-vascular tissues caused vascular changes, subacute inflammatory cells infiltration, granulomatous nodules and scarring lesions. These alterations corresponded to the successive stages of an inflammatory process. No correlation noted between tissular lesions, delay of filarial infestations and number of microfilariae in the "snip". The presence of lesions in one or several tissular areas demonstrated that extravascular escaping of microfilariae was not synchronous. Symptomatology of filariasis depended on the localization of the lesions. Similarities between the lesions noted in murids Lemniscomys striatus L. and those observed in man showed that the 2 isolates of Monanema spp. used in this study were very close to O. volvulus in the pathological domain. They might be considered as a valuable and reproducible experimental model.