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Biomedical subjects

M Mahieu

Publications and source records attributed to M Mahieu.

At least 19 recordsLinked to original sources

Impact on productivity of peri-parturient rise in fecal egg counts in Creole goats in the humid tropics.

The control of gastrointestinal nematodes requires an understanding of their epidemiology so that particular parasite stages can be targeted. Dam infection during early lactation is one example of this in ruminant nematode infections. The existence of the peri-parturient relaxation in immunity and its impact on productivity were examined in a Creole goat flock from Guadeloupe, exposed to mixed natural infection (predominantly Haemonchus contortus and Trichostrongylus colubriformis). A total of 1,511 l were obtained from 909 does resulting from 463 dams and 150 sires. Fecal and blood samples were collected at kidding before anthelmintic drenching, 4 and 6 weeks after kidding. The traits analyzed were logarithm transformed fecal egg counts (FEC), packed cell volume (PCV), and logarithm transformed blood eosinophilia counts (EOS) for does at each sampling point and changes in these during the postpartum period. With the exception of the PCV values measured at kidding, lactating does had significantly higher FEC and lower PCV than control dry does at every sampling point. Geometric means of FEC in lactating does were 819 +/- 174, 677 +/- 146 and, 699 +/- 160 eggs per gram (EPG) at kidding, 4 and 6 weeks after kidding respectively. Geometric means of FEC in dry does were 187 +/- 57, 89 +/- 28, 133 +/- 43 at these time points, respectively. EOS differences were not consistent between groups and probably not specific enough for variations in Creole goats' peri-parturient rise to be discussed. As does aged, their egg output decreased and primiparous does always had greater egg output than multiparous ones. Overall, does' FEC at 4 weeks after kidding decreased by 1.3% each year. The higher the litter size, the higher the FEC at kidding and inverse applied for PCV measurements. Does that stopped lactating had significantly lower FEC and higher PCV values than lactating does with low milk yields. Higher infection rates during early lactation in Creole goats were recorded in does with lower maternal ability assessed by the average daily weight gain of kids between 10 and 30 days of age. Kids from dams with higher FEC (i.e. >600 EPG higher than corresponding does) had 17% lower average daily weight gain between 30 and 70 days postpartum and were approximately 1 kg lighter at weaning than kids from dams with lower FEC. Thus, it is clear that a peri-parturient rise in FEC exists in Creole goats. By controlling the intensity of this peri-parturient rise in FEC, herd health and productivity could be substantially improved.

Animals↗

Preweaning productivity of suckling goats and sheep in Guadeloupe (FWI) under intensive reproductive rate and grazing management.

In Guadeloupe, small ruminants are reared for meat production under pasture conditions. Intensive rotative grazing systems (irrigated, fertilized and high-stocked tropical pastures) allow satisfactory levels of production but generate high post-grazing residues. Experiments were designed to control these. A system in which residuals were mown (RM) was tested in comparison to the control system (residuals remained, RR). The same design was carried out over two years with Creole goats and Martinik sheep. An accelerated reproductive rate (3 parturitions over 2 years) was carried out. Systems were compared at three parturition seasons per year (dry, intermediate and rainy seasons). Each group was composed of 20 goats (36.0+/-2.5 kg) or 20 ewes (46.8+/-2.4 kg). The systems exhibited high levels of productivity in both species compared to other results in the tropics: more than 50 and 30 offspring born alive per hectare and per reproductive season for the goat and ewe flocks, respectively. The annual production at birth was 110 kg kids/ha per year and 133 kg lambs/ha per year (i.e. 21% more). Corresponding values at weaning were 630 kg kids/ha per year and 785 kg lambs/ha per year (i.e. 25% more). The RM system produced 10% more than the RR system in Creole goats, while it produced 35% more in Martinik sheep. Seasonal effects and other factors of variation are discussed.

Animal Husbandry↗

Pharmacological profile of (2R-trans)-4-[1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-acetamide (S)-Hydroxybutanedioate (R116301), an orally and centrally active neurokinin-1 receptor antagonist.

In comparison with a series of reference compounds, (2R-trans)-4-[1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinyl]-N-(2,6-dimethylphenyl)-1-acetamide (S)-Hydroxybutanedioate (R116301) was characterized as a specific, orally, and centrally active neurokinin-1 (NK(1)) receptor antagonist with subnanomolar affinity for the human NK(1) receptor (K(i): 0.45 nM) and over 200-fold selectivity toward NK(2) and NK(3) receptors. R116301 inhibited substance P (SP)-induced peripheral effects (skin reactions and plasma extravasation in guinea pigs) and a central effect (thumping in gerbils) at low doses (0.08-0.16 mg/kg, s.c. or i.p.), reflecting its high potency as an NK(1) receptor antagonist and excellent brain disposition. Higher doses blocked various emetic stimuli in ferrets, cats, and dogs (ED(50) values: 3.2 mg/kg, s.c.; 0.72-2.5 mg/kg, p.o.). Even higher doses (11-25 mg/kg, s.c.) were required in mice (capsaicin-induced ear edema) and rats (SP-induced extravasation and salivation), consistent with lower affinity for the rodent NK(1) receptor and known species differences in NK(1) receptor interactions. R116301 inhibited the ocular discharge (0.034 mg/kg) but not the dyspnoea, lethality, or cough (>40 mg/kg, s.c.) induced by [betaALA(8)]-neurokinin A (NKA) (4-10) in guinea pigs, attesting to NK(1) over NK(2) selectivity. R116301 did not affect senktide-induced miosis (>5 mg/kg, s.c.) in rabbits, confirming the absence of an interaction with the NK(3) receptor. R116301 was inactive in guinea pigs against skin reactions induced by histamine, platelet-aggregating factor, bradykinin, or Ascaris allergens (>10 mg/kg, s.c.). In all species, R116301 showed excellent oral over parenteral activity (ratio, 0.22-2.7) and a relatively long duration (6.5-16 h, p.o.). The data attest to the specificity and sensitivity of the animal models and support a role of NK(1) receptors in various diseases.

Administration, Oral↗

Fatal aplastic anaemia associated with clopidogrel.

Clopidogrel, an inhibitor of platelet aggregation, was initially thought to be free of the side-effects of ticlopidine. We describe a man who developed aplastic anaemia after 5 months of treatment with clopidogrel. There were no other plausible causes. We suggest that his fatal aplastic anaemia might have been induced by clopidogrel.

Aged↗

[Iron overload and myelodysplastic syndromes].

Transfusion of RBC units, the only current treatment for many myelodysplastic syndromes, and excess intestinal absorption of Fe related to dyserythopoiesis often result in iron overload. This condition is associated with high rates of morbidity and mortality. High-risk patients include those with refractory anemia, sideroblastic anemia, 5q-syndrome, patients with a good prognosis (low or lower intermediate international prognosis score), patients having received over 100 RBC units, and patients under the age of 70. Deferoxamine, while it can prevent iron overload, is a strenuous treatment requiring 8-to-12 hour-overnight subcutaneous injections. When patients comply with the regimen, it efficiently prevents mortality due to iron overload, but must be implemented early in the disorder, usually before transfusing 20 RBC concentrates. A simple way of monitoring iron overload is to measure seric ferritin levels and record the number of RBC concentrates. The chelating treatment should be modulated according to age, MDS type, international prognosis score, number of RBC units received, ferritin levels, and most of all, patient tolerance. The direct subcutaneous approach is currently being evaluated by the French Group for Myelodysplasias for its efficiency to prevent disorders, but seems to be both efficient and well complied with (a national protocol is under way). The recent findings on the proteins implied in iron recycling by macrophages after destruction of RBCs, may in the long term, enable us to manage patients with less burdensome treatments and more effective new oral chelates.

Administration, Oral↗

Optimization of debris removal during bladder irrigation.

Debris build-up within the bladder is one of the main problems encountered by patients undergoing long term catheterization. One of the methods of ameliorating this is to wash out the bladder at regular intervals. In this paper, an alternative method of bladder irrigation is investigated experimentally. The effectiveness of several possible catheter designs has been examined, together with other relevant variables such as the proximity and alignment of the tube tip to the debris and the irrigation flow rate. Results show that debris removal is very sensitive to tube design, with best designs achieving almost complete removal and the worst practically none. The proprietary continuous irrigation catheter used was particularly poor for the type of debris used. Removal is insensitive to the distance of the tube tip from the bladder base up to a limiting value, above which it reduces rapidly. Where misalignment causes the inlet jet to miss the debris, removal rates are very low. Increasing flow rate increases removal up to a limiting value, above which it remains constant. Although the results show the general trends, to optimize the system requires further understanding of the detailed flow patterns within the bladder. A theoretical study using computational fluid dynamics is thus being undertaken.

Administration, Intravesical↗

Interferon-gamma and interleukin-6 inhibit proliferation in human melanoma cells by different signalling pathways.

Interferon regulatory factor-1 (IRF-1) is a cell growth inhibitor, induced by cytokines, which transactivates downstream effector genes. The role of IRF-1 in the antiproliferative effect of interleukin-6 (IL-6) was investigated using the A375 human melanoma cell line. IL-6 is a stronger inhibitor of A375 proliferation compared with interferon-gamma (IFNgamma). However, in contrast to IFNgamma, IL-6 triggered lower IRF-1 DNA binding activity and induced barely detectable IRF-1-dependent transactivation activity. Furthermore, although IFNgamma induces only activation of signal transducer and activator of transcription (STAT) 1, IL-6 activates mainly STAT3. These data suggest that IRF-1 plays a minor role in the antiproliferative effect of IL-6, which uses alternative signalling events to induce growth inhibition in A375 melanoma cells.

Cell Division↗

[Tuberculosis, mycobacterium infection and hairy cell leukemia].

OBJECTIVES: Diagnosis of tuberculosis and/or mycobacteria infection is particularly difficult in immunocompromised patients. PATIENTS AND METHODS: We examined the clinical presentation, means of diagnosis, treatment and outcome of tuberculosis in a retrospective study of 6 patients among 75 with hairy cell leukemia diagnosed from 1982 to 1995. RESULTS: Hearlding symptoms of tuberculosis diagnosis were: fever (6/6), weight loss (4/6), pleural effusion (1/6), superficial adenopathy (1/6), persistence of cytopenia or splenomegaly during the treatment of hairy cell leukemia. Pulmonary symptoms were present in only two cases. Diagnosis was obtained by positive culture of mycobacteria in 2 cases (Mycobacterium tuberculosis in pleural effusion, Mycobacterium kansaii in adenopathy). Microbiological diagnosis was never obtained from sputum (6/6). Diagnosis was obtained by histopathology in all cases: from bone marrow (2 cases), lymph nodes (2 cases), liver (1 case), spleen (1 case), umbilical fat (1 case). Tuberculosis was disseminated in all cases. By clinical, biological, microbiological histopathological means and response to treatment, tuberculosis was considered as: hematopoietic in all cases, hepatic (in 4/6), pleural (1/6), pulmonary (1/6). A favorable outcome of tuberculosis was observed in all cases. No death was observed. CONCLUSIONS: Tuberculosis was found in 8% of hair cell leukemia patients. In hairy cell leukemia, tuberculosis is characterized by few pulmonary symptoms and scarse microbiological documentation. In contrast, histopathology is very interesting to confirm diagnosis. Tuberculosis is in most cases disseminated and in particular hematopoietic diffusions is always present. In spite of existensive localization, the prognosis remains excellent and all patients can be cured. In our opinion, this good prognosis may be linked to the improvement of hairy cell leukemia treatment observed since the advent of interferon pentostatin and 2cdA.

Adult↗

[POEMS syndrome].

POEMS syndrome is an acronym defined by Bardwick (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal component and Skin changes). Other various clinical and biological features are reported: edema, cachexia, microangiopathic glomerulopathy, most rarely pulmonary hypertension, cutaneous necrosis. Thrombocytosis or polycythemia may be a prominent feature. POEMS syndrome is sometimes associated with lymphoproliferative disorder. Castelman-like disease is frequently observed as pathologic findings on lymph nodes. Distinction between POEMS syndrome and osteosclerotic myeloma is delicate. The rate of the monoclonal protein is modest-always less than 30 g/L-and is almost of the lambda light chain class. In contrast to multiple myeloma this syndrome is rarely associated with hypercalcemia, skeletal fracture, renal involvement and increasing of M component during evolution. Bone marrow plasmocytosis is usually less than 15% and the kinetic phenotype and genetic characteristics of the plasma cell remain those found in monoclonal gammopathy of undetermined significance. The pathophysiology of this syndrome remains largely unknown but overproduction of pro-inflammatory cytokines are reported, especially TNF alpha, IL-6 and IL-1 beta. Some clinical manifestations seem to be cytokine related. Polyneuropathy and cachexia are the main cause of death. A part corticosteroid and cure of solitary bone lesion, treatment is disappointing and survival is 60% at five years.

Humans↗