Does stoma modify compliance with enhanced recovery after surgery programs? Results of a cohort study.

PURPOSE: Few studies have focused on enhanced recovery programs (ERPs) in patients who have received a stoma after colorectal surgery. The objective of the study was to compare ERP compliant patients who have not received a stoma, those who received a colostomy, and those who received an ileostomy. METHODS: This study used data that had been prospectively collected as part of the ERP audit performed through the Groupe francophone de Réhabilitation Améliorée après Chirurgie [Francophone Group for Enhanced Recovery after Surgery] over a 4-year period. All patients who had undergone colorectal surgery were included and separated into three groups (no stoma, ileostomy, and colostomy). The primary outcome was ERP compliance, calculated through the use of 16 tracer items. RESULTS: Of the 422 recruited patients, 317 had not received a stoma (75.12%), 59 had an ileostomy (13.98%), and 46 had a colostomy (10.90%). ERP compliance was 73% in the non-stoma group, 66.6% in the ileostomy group, and 66% in the colostomy group (p < 0.001). Multivariate analysis showed that patients from the ileostomy group had a higher risk of bowel preparation [OR = 9.1; 95% CI = 1.16-71.65] and of maintaining their urinary catheter [OR = 0.3; 95% CI = 0.14-0.81] than the group which did not receive a stoma. Patients from the colostomy group required significantly more drainage than those in the non-stoma group (OR = 4.3; 95% CI = 1.33-14.02). CONCLUSION: ERP is feasible in colorectal surgery in the context of stomas, but in case of ileostomy protecting a rectal surgery, the audit system must be adapted to the protocols in use in the departments.

Floristic evidence for alternative biome states in tropical Africa.

The idea that tropical forest and savanna are alternative states is crucial to how we manage these biomes and predict their future under global change. Large-scale empirical evidence for alternative stable states is limited, however, and comes mostly from the multimodal distribution of structural aspects of vegetation. These approaches have been criticized, as structure alone cannot separate out wetter savannas from drier forests for example, and there are also technical challenges to mapping vegetation structure in unbiased ways. Here, we develop an alternative approach to delimit the climatic envelope of the two biomes in Africa using tree species lists gathered for a large number of forest and savanna sites distributed across the continent. Our analyses confirm extensive climatic overlap of forest and savanna, supporting the alternative stable states hypothesis for Africa, and this result is corroborated by paleoecological evidence. Further, we find the two biomes to have highly divergent tree species compositions and to represent alternative compositional states. This allowed us to classify tree species as forest vs. savanna specialists, with some generalist species that span both biomes. In conjunction with georeferenced herbarium records, we mapped the forest and savanna distributions across Africa and quantified their environmental limits, which are primarily related to precipitation and seasonality, with a secondary contribution of fire. These results are important for the ongoing efforts to restore African ecosystems, which depend on accurate biome maps to set appropriate targets for the restored states but also provide empirical evidence for broad-scale bistability.

Exposure to HIV-protease inhibitors selects for increased expression of P-glycoprotein (ABCB1) in Kaposi's sarcoma cells.

BACKGROUND: Given that HIV-protease inhibitors (HIV-PIs) are substrates/inhibitors of the multidrug transporter ABCB1, can induce ABCB1 expression, and are used in combination with doxorubicin for AIDS-Kaposi's Sarcoma (KS) treatment, the role that ABCB1 plays in mediating multidrug resistance (MDR) in a fully transformed KS cell line (SLK) was explored. METHODS: The KS cells were exposed to both acute and chronic treatments of physiological concentrations of different HIV-PIs (indinavir, nelfinavir, atazanavir, ritonavir, or lopinavir), alone or together with doxorubicin. The ABCB1 mRNA and protein expression levels were then assessed by qRT-PCR and western blotting, flow cytometry, and immunofluorescence. RESULTS: Chronic treatment of SLK cells with one of the five HIV-PIs alone or together resulted in increased resistance to doxorubicin. Co-treatment with one of the HIV-PIs in combination with doxorubicin resulted in a synergistic increase in resistance to doxorubicin, and the degree of resistance was found to correlate with the expression of ABCB1. The SLK cells were also revealed to be cross-resistant to the structurally unrelated drug paclitaxel. CONCLUSION: These studies suggest that ABCB1 is primarily responsible for mediating MDR in SLK cells selected with either HIV-PIs alone or in combination with doxorubicin. Therefore, the roles that ABCB1 and drug cocktails play in mediating MDR in KS in vivo should be evaluated.

Estimates of Maize Plant Density from UAV RGB Images Using Faster-RCNN Detection Model: Impact of the Spatial Resolution.

Early-stage plant density is an essential trait that determines the fate of a genotype under given environmental conditions and management practices. The use of RGB images taken from UAVs may replace the traditional visual counting in fields with improved throughput, accuracy, and access to plant localization. However, high-resolution images are required to detect the small plants present at the early stages. This study explores the impact of image ground sampling distance (GSD) on the performances of maize plant detection at three-to-five leaves stage using Faster-RCNN object detection algorithm. Data collected at high resolution (GSD ≈ 0.3 cm) over six contrasted sites were used for model training. Two additional sites with images acquired both at high and low (GSD ≈ 0.6 cm) resolutions were used to evaluate the model performances. Results show that Faster-RCNN achieved very good plant detection and counting (rRMSE = 0.08) performances when native high-resolution images are used both for training and validation. Similarly, good performances were observed (rRMSE = 0.11) when the model is trained over synthetic low-resolution images obtained by downsampling the native training high-resolution images and applied to the synthetic low-resolution validation images. Conversely, poor performances are obtained when the model is trained on a given spatial resolution and applied to another spatial resolution. Training on a mix of high- and low-resolution images allows to get very good performances on the native high-resolution (rRMSE = 0.06) and synthetic low-resolution (rRMSE = 0.10) images. However, very low performances are still observed over the native low-resolution images (rRMSE = 0.48), mainly due to the poor quality of the native low-resolution images. Finally, an advanced super resolution method based on GAN (generative adversarial network) that introduces additional textural information derived from the native high-resolution images was applied to the native low-resolution validation images. Results show some significant improvement (rRMSE = 0.22) compared to bicubic upsampling approach, while still far below the performances achieved over the native high-resolution images.

Crystal and electronic structures of magnesium(II), copper(II), and mixed magnesium(II)-copper(II) complexes of the quinoline half of styrylquinoline-type HIV-1 integrase inhibitors.

A new target in AIDS therapy development is HIV-1 integrase (IN). It was proven that HIV-1 IN required divalent metal cations to achieve phosphodiester bond cleavage of DNA. Accordingly, all newly investigated potent IN inhibitors contain chemical fragments possessing a high ability to chelate metal cations. One of the promising leads in the polyhydroxylated styrylquinolines (SQLs) series is (E)-8-hydroxy-2-[2-(4,5-dihydroxy-3-methoxyphenyl)-ethenyl]-7-quinoline carboxylic acid (1). The present study focuses on the quinoline-based progenitor (2), which is actually the most probable chelating part of SQLs. Conventional and synchrotron low-temperature X-ray crystallographic studies were used to investigate the chelating power of progenitor 2. Mg2+ and Cu2+ cations were selected for this purpose, and three types of metal complexes of 2 were obtained: Mg(II) complex (4), Cu(II) complex (5) and mixed Mg(II)-Cu(II) complexes (6 and 7). The analysis of the crystal structure of complex 4 indicates that two tridentate ligands coordinate two Mg2+ cations, both in octahedral geometry. The Mg-Mg distance was found equal to 3.221(1) A, in agreement with the metal-metal distance of 3.9 A encountered in the crystal structure of Escherichia coli DNA polymerase I. In 5, the complex is formed by two bidentate ligands coordinating one copper ion in tetrahedral geometry. Both mixed Mg(II)-Cu(II) complexes, 6 and 7 exhibit an original arrangement of four ligands linked to a central heterometallic cluster consisting of three octahedrally coordinated magnesium ions and one tetrahedrally coordinated copper ion. Quantum mechanics calculations were also carried out in order to display the electrostatic potential generated by the dianionic ligand 2 and complex 4 and to quantify the binding energy (BE) during the formation of the magnesium complex of progenitor 2. A comparison of the binding energies of two hypothetical monometallic Mg(II) complexes with that found in the bimetallic magnesium complex 4 was made.

[Predictive value of D-dimer assay in superficial thrombophlebitis of the lower limbs]. / Valeur des D-dimères lors des thromboses veineuses superficielles des membres inférieurs.

OBJECTIVE: The negative predictive value of D-dimer (DD) assay in patients with venous thromboembolic disease is well established for deep vein thrombosis and pulmonary embolism. Little is known about the value of DD assay in patients with superficial thrombophlebitis (ST). The purpose of this study was to assess the value of DD assay in patients with ST of the lower limb. METHOD: The study group was composed of 100 consecutive patients, irrespective of age. Patients with clinical manifestations suggestive of ST of the lower limbs with positive duplex color Doppler evidence confirming the diagnosis and DD assay results (Vidas D-Dimer Exclusion) within 24 hours were included in the study. Patients with thrombosis in another site in addition to the superficial vein of the lower limb, those taking anticoagulants for more than 48 hours, and those with a condition known to potentially elevate DD levels were excluded. The volume of the thrombus was determined echographically and reported as mean diameter and length. RESULTS: Sixty-two women and 38 men were included. Mean age (+/- 5) was 58 years +/- 13.48 (range 18-90; median: 57). The ST involved the Great saphenous (n=74), the small saphenous (n=11) or another vein (n=15). Mean thrombus volume was 4453 mm(3) +/- 7101 (range 94-38484; median: 1751). Mean DD level was 829 ng/ml +/- 516.72 (range 100-2567; median: 715.5). DD assay was negative (<500 ng/ml) in 32 patients (32%) and positive in 68 (68%). For these three items, there was no significant difference between ST with and without varicose veins. DD assay was always positive (>or=500 ng/ml) in all patients aged over 70 years (n=22). In patients aged less than 70 years (n=78), DD assay was positive in 46 (59%) and negative in 32 (41%). DD level was positively correlated with thrombus volume in patients aged less than 70 years (P<0.0001). ROC analysis, sensitivity as a function of specificity by thrombus volume for the entire population, determined the usefulness of a negative DD assay. Considering the critical threshold at 5914 mm(3), sensitivity was 1.0 (95CI 0.89-1.0), with 0.29 specificity (95CI 0.19-0.42), 1.00 negative predictive value and 0.75 positive predictive value. However, the thrombus volume was less than this threshold value in three of the nine cases of ST with extension to the terminal portion of the saphenous. CONCLUSION: A positive DD assay was observed in 68% of patients with ST, with no significant difference with or without varicose veins. The test was positive in all patients aged over 70 years and in 59% of those aged under 70 years. There was a correlation between DD level and thrombus volume, yielding a threshold volume (5914 m(3)) above which all DD tests were positive. Nevertheless, this threshold volume was too great to include all ST extending to the terminal portion of the saphenous. Measurement of DD level is thus not contributive to the diagnosis of ST.

Long-term risk of venous thromboembolism recurrence after isolated superficial vein thrombosis.

Essentials Long-term risk of recurrence of isolated superficial vein thrombosis (SVT) is under-studied. We analyzed data from a cohort of first SVT and proximal deep vein thrombosis (DVT) without cancer. The risk of recurrence as DVT or pulmonary embolism is twice lower in SVT patients. However, overall risk of recurrence is similar between SVT and proximal DVT patients. Click to hear Dr Decousus' perspective on superficial vein thrombosis SUMMARY: Background Isolated superficial vein thrombosis (iSVT) (without concomitant deep vein thrombosis [DVT] or pulmonary embolism [PE]) is a frequent event, but available data on long-term outcomes are scarce and retrospective. Therefore, we aimed to determine prospectively the risk and type of venous thromboembolism (VTE) recurrence after iSVT and compare them with those of proximal DVT. Methods Using data from the prospective, multicenter, observational, OPTIMEV study, we assessed, at 3 years and after anticoagulants were stopped, the incidence and the type of VTE recurrence (iSVT/DVT/PE) of patients with a first objectively confirmed iSVT without cancer (n = 285), and compared these with those of patients with a first proximal DVT without cancer (n = 262). Results As compared with proximal DVT patients, iSVT patients had a similar overall incidence of VTE recurrence (5.4% per patient-year [PY] versus 6.5% per PY, adjusted hazard ratio [aHR] 0.9, 95% confidence interval [CI] 0.5-1.6), but iSVT recurred six times more often as iSVT (2.7% versus 0.6%, aHR 5.9, 95% CI 1.3-27.1) and 2.5 times less often as deep-VTE events (2.5% versus 5.9%, aHR 0.4, 95% CI 0.2-0.9). Varicose vein status did not influence the risk or the type of VTE recurrence. Saphenian junction involvement by iSVT was not associated with a higher risk of recurrence (5.2% per PY versus 5.4% per PY), but was associated with recurrence exclusively as deep-VTE events. Conclusion In patients with a first iSVT without cancer, after stopping anticoagulants, the incidence of deep-VTE recurrence is half that of DVT patients, but the overall risk of recurrence is similar. Ssaphenian junction involvement seems to influence the risk of deep-VTE recurrence, whereas varicose vein status has no impact or a low impact on VTE recurrence.

[Recurrent varices at the groin and popliteal fossa after surgical treatment]. / Récidive de varices à l'aine et à la fosse poplitée après traitement chirurgical.

Patients who undergo surgery involving the groin and the popliteal fossa often develop recurrent varices which require careful management. Several surveys using various classification systems have estimated the prevalence of recurrent varices after groin and popliteal surgery. Patients may seek medical care for various reasons: unsightly recurrent varicose veins, vein-related symptoms, appearance of cutaneous or subcutaneous changes, concerns about the health risk related to their veins or limitation of activity. Recurrent varices may also be found at routine follow-up examinations. An analysis of recurrence at this location reveals three main mechanisms: incomplete resection of the saphenofemoral or saphenopopliteal junctions in patients with an initially incompetent terminal valve. The persisting reflux feeds the tributaries connected at the saphenous stump; the second mechanism is related to neovascularisation that reconnects the deep venous system with the superficial network; the neo-veins are valveless. This phenomenon appears to be more frequent when the resection of the saphenous vein ending has been complete; the third mechanism is due to a tactical error; the refluxive pelvic veins that had not been diagnosed feed the varices. Duplex scanning identifies the different possible mechanisms and provides anatomical and hemodynamic data. Interventional treatment methods after varices recurrence are redosurgery, sclerotherapy and pelvic vein embolization when they are at issue. All these methods are described in details. Results provided by these treatments are analysed. Unfortunately no randomized control study enables grade A or B recommendations. Personally we suggest that ultrasound guided foam sclerotherapy should be the first-line treatment except when duplex scanning reveals an intact incompetent saphenous stump at the saphenofemoral junction or/and saphenopopliteal junction with a massive reflux filling the varicose network.

Seeing Central African forests through their largest trees.

Large tropical trees and a few dominant species were recently identified as the main structuring elements of tropical forests. However, such result did not translate yet into quantitative approaches which are essential to understand, predict and monitor forest functions and composition over large, often poorly accessible territories. Here we show that the above-ground biomass (AGB) of the whole forest can be predicted from a few large trees and that the relationship is proved strikingly stable in 175 1-ha plots investigated across 8 sites spanning Central Africa. We designed a generic model predicting AGB with an error of 14% when based on only 5% of the stems, which points to universality in forest structural properties. For the first time in Africa, we identified some dominant species that disproportionally contribute to forest AGB with 1.5% of recorded species accounting for over 50% of the stock of AGB. Consequently, focusing on large trees and dominant species provides precise information on the whole forest stand. This offers new perspectives for understanding the functioning of tropical forests and opens new doors for the development of innovative monitoring strategies.

Collagen and lipid biosynthesis in a case of epitheliogenesis imperfecta in cattle.

An analysis of the dermis and a study of collagen and lipid biosynthesis by fibroblast cultures were carried out in one case of epitheliogenesis imperfecta in a new born calf. This was found to be not only an epidermal disease with fissures and blisters within basal cells on the basement membrane but also a metabolic disease affecting the dermal fibroblasts. These fibroblasts showed a significant decrease in collagen biosynthesis with an increase in the percentage of type III collagen and also a decrease in the biosynthesis of lipids, especially glycerides and cholesterol.

Axonal transport of rabies virus in the central nervous system of the rat.

Stereotaxic inoculation of rabies virus into specific nuclei in the central nervous system has been used for the investigation of the central neural transport mechanisms of viral information. The infection was monitored by specific fluorescence and peroxidase studies and the titration of viral infectivity in dissected brain areas. Twenty-four hours after inoculation into the striatum, cortex, or substantia nigra, infected neurons were detected only in cells from areas and nuclei which were related to the site of inoculation. The distribution of infected neurons showed that retrograde axoplasmic flow plays a determining role in the transport of rabies virus 24 hours after delivery of virus to specific target nuclei. Local destruction of neurons by kainic acid at the site of viral inoculation did not prevent the uptake and subsequent retrograde axonal transport of virus. There was an overall correlation between the major neural connections of the inoculated areas (e.g. the striatum) and the infected areas 24 hours later (e.g. the substantia nigra).

Inhibition of the transport of rabies virus in the central nervous system.

The effect of colchicine, an inhibitor of axonal transport, on the spread of rabies virus in the central nervous system was investigated using Wistar rats. Colchicine was inoculated into the striatum at various times before and after inoculation of rabies virus into the same site. Rats were killed at various times after viral inoculation and the spread of rabies virus was monitored by rabies immunofluorescence of selected areas of brain. The most effective inhibitory effect was obtained by colchicine treatment applied two days before virus inoculation. Under these conditions, no fluorescent foci could be detected until day 3 post-infection whereas control rats exhibited infected cells as soon as two days post-infection. This inhibitory effect is reversible and the general consequence seems to be a delay in the rate of viral spread. However, five days after the virus challenge, some major brain areas were still partially preserved from infection (striatum, frontal cortex, pyriform cortex). Ten days after colchicine treatment, the microtubules have recovered their capacity to transport the virus. At the onset of paralysis, the general pattern of infection in brain sections from colchicine-treated rats was not significantly different from that of control rats. This inhibitory effect on the transport of rabies virus can be prolonged by administration of additional colchicine.

A randomized comparison of the effect of four antihypertensive monotherapies on the subjective quality of life in previously untreated asymptomatic patients: field trial in general practice. The OCAPI Study Group. Optimiser le Choix d'un Anti-hypertenseur de Première Intention.

OBJECTIVE: To assess the equivalence of four antihypertensive treatments in patients with mild-to- moderate hypertension, and to compare the effects of those drugs on the subjective quality of life and clinical safety. DESIGN, SETTING AND PATIENTS: 653 patients aged > or = 18 years with untreated hypertension were randomly allocated to receive a combination of two diuretics (altizide and spironolactone), a beta-blocker (bisoprolol), a calcium antagonist (verapamil), or an angiotensin converting enzyme (ACE) inhibitor (enalapril). Follow-up lasted for 1 year. MAIN OUTCOME MEASURES: A composite outcome of the following measures was used to define success: attendance at the 12-month visit; at least nine supine DBP measurements during the study; and median supine DBP < 90 mmHg and a reduction of at least 10 mmHg compared with the baseline value. Failure was defined as one or more of those criteria not being fulfilled. Equivalence was concluded if the 95% confidence interval for the success rates differed between two groups by less than +/- 10%. Clinical safety and subjective quality of life were also assessed. RESULTS: No statistically significant differences in the change in DBP or systolic blood pressure were observed between the groups. The success rates were 43.9, 42.0, 32.5 and 43.9% in diuretic, beta-blocker, calcium antagonist and ACE inhibitor groups, respectively. Equivalence between the treatments could not be concluded, although analysis with a larger equivalence interval showed that some comparisons indicated equivalence. Significant improvement in satisfaction was observed for certain items for subjective quality of life at 1 month in the calcium antagonist treatment group, and significant differences in the responses to the clinical safety questionnaire were observed after 1-month follow-up in calcium antagonist and beta-blocker groups. Differences were no longer significant after 9 months. CONCLUSIONS: These results do not provide evidence on the basis of efficacy of blood pressure lowering or ability to increase short-term (1-year) safety and quality of life favouring any particular treatment among the studied drugs for newly diagnosed patients with mild-to-moderate hypertension.

Increase in PaO2 following intravenous administration of propranolol in acutely hypoxemic patients.

To define the effects of beta-blockade therapy on PaO2, arterial blood gas levels were determined before and after therapeutic administration of propranolol in 44 acutely ill patients. With a FIo2 of 0.33 +/- 0.08, the PaO2 increased from 89.6 +/- 3.6 to 95.3 +/- 3.8 mmHg (p less than 0.01), 10 minutes after intravenous administration of 1 to 3 mg of propranolol. Simultaneous hemodynamic measurements obtained in six patients demonstrated a dramatic decrease in venous admixture, associated with decreases in cardiac output and mixed venous Po2. Propranolol administration generally results in a moderate increase in PaO2, which is related to a significant decrease in pulmonary shunt. The clinical implications of these findings are limited by the expected decrease in tissue oxygen delivery after beta-blockade therapy.

The effects of diet, ad Libitum feeding, and moderate and severe dietary restriction on body weight, survival, clinical pathology parameters, and cause of death in control Sprague-Dawley rats.

A 2-year study was conducted in Sprague-Dawley rats to compare the effects of ad libitum (AL) feeding and dietary restriction (DR) on body weight, survival, cause of death, and clinical pathology parameters. Three groups of 120 rats/sex each received the following daily rations of a maintenance rodent diet: ad libitum (AL group); 75% of adult AL food consumption (25% DR group); and 45% of adult AL food consumption (55% DR group). Among the 3 groups, there were generally no differences in relative (food intake per gram of body weight) food consumption. Compared to the AL group, decreased body weight gain occurred in DR groups and was associated with an increase in survival proportional to the DR rate. The main cause of death was pituitary adenomas in all groups. Decreases in total leukocyte, segmented neutrophil, lymphocyte, and platelet counts occurred in the 55% DR group. In serum biochemistry, there were decreases in total protein, albumin, total and HDL cholesterol, and total calcium, and increases in alkaline phosphatase activities and chloride in 55% DR females, as well as decreases in triglycerides in the 55% DR group and in 25% DR females. Results of urinalyses showed decreases in urine volume and protein, and increases in urinary pH in both DR groups. In conclusion, a DR rate of approximately 25% appears to be appropriate for Sprague-Dawley rats in toxicity and carcinogenicity assays to improve survival without impairing growth and routine clinical pathology parameters.

Description of a short-term Taxol-induced nociceptive neuropathy in rats.

This work describes a new animal model of neuropathic pain produced by the single intraperitoneal administration of Taxol (32 mg/kg) to male Sprague-Dawley rats. During the course of the experiment, the clinical status of the rats remained satisfactory and motor function was not altered. A number of classical behavioural tests of nociception as well as histological and electrophysiological investigations were performed. Taxol administration produced an important and rapidly developing mechanical hyperalgesia, a thermal hypoalgesia but no mechanical or thermal allodynia. Degenerative changes were observed in the sciatic nerve, the nerve fibres in the paw subcutaneous tissue and in the lumbar spinal cord. When Taxol or vehicle (a mix of Cremophor and ethanol) were repeatedly injected once a week for 5 weeks, similar nociceptive disorders were observed in addition to a decrease in peripheral nerve conduction velocity. The selective dysfunction of high-diameter myelinated fibres observed after one single administration of Taxol (32 mg/kg) may be attributable to paclitaxel-induced neuropathy, however other mechanisms causing neurochemical dysfunction must also be involved.

Predictive value of hormonal profiles before stimulation for in vitro fertilization.

Ovarian responses to stimulation for in vitro fertilization by clomiphene citrate menotropins have been correlated to the hormonal profiles determined during spontaneous cycles. The authors found 80% of high plasmatic luteinizing hormone (LH) and/or androgens levels associated with an inappropriated response: premature LH surge, multifollicular ovarian response, or dissociated cystic response, versus only 11% with appropriated responses. High plasmatic follicle-stimulating hormone existed in 71% of the no response group. Detryptoréline, a luteinizing hormone-releasing hormone agonist associated with menotropins, in a "short procedure" maintained the adequate responses and suppressed premature LH surges. The no response group was moderately improved, as were multifollicular and dissociated cystic response groups. Hormonal profiles could be useful predictive factors of the ovarian response for adaptation on the first procedure of stimulation.

alpha-Difluoromethylornithine induces protective immunity in mice inoculated with Plasmodium berghei sporozoites.

Mice inoculated weekly with Plasmodium berghei sporozoites while under treatment with alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, developed protective immunity against subsequent challenge with this parasite. The percentage of mice protected was similar whether DFMO alone (55%) or DFMO + chloroquine (65%) was used. With chloroquine alone, only 12% of mice were protected. This protection was long-lasting (at least six months). The immunity protected against sporozoites but not against erythrocytic form inoculation. It is suggested that this protection is induced by antigens released from exoerythrocytic schizonts whose further development is inhibited by DFMO.

Assessment of neurotoxicity following repeated cremophor/ethanol injections in rats.

As the mixture cremophor/ethanol is known to have side-effects affecting the peripheral nervous system, we have assessed its behavioural and morphological neurotoxicity after repeated intraperitoneal injections in male Sprague Dawley rats. Clinical status of the animals was good throughout the experiment and no motor deficits were observed. Nevertheless, sensory testing demonstrated an hyperalgesia and an allodynia to mechanical stimuli, associated to peripheral axon degeneration.

Induction of amenorrhea during hormone replacement therapy: optimal micronized progesterone dose. A multicenter study.

The effects of oral micronized progesterone on the endometrium and bleeding pattern have been assessed in a multicenter study of 101 postmenopausal patients. During a minimum of 6 cycles, the participants received either percutaneous 17 beta-estradiol (1.5 mg/day) associated with micronized progesterone (100 mg/day), given at bedtime for 21/28 days or 25 days/calendar month (n = 98) [1], or E2 (3 mg/day) for 25 days associated with progesterone (300 mg/day), from day 16 to day 25 (n = 3) [2], according to their willingness to induce, or not, cyclic withdrawal bleeding. Each endometrial biopsy performed at 6-month minimum was assessed by two independent pathologists: results showed 61% quiescent without mitosis, 23% mildly active with very rare mitoses and 8% partial secretory endometrium. The remaining biopsies showed inadequate tissue (4%) or a sub-atrophy (4%). No hyperplasia was found by any pathologist. In the case of inadequate material, the mean thickness of endometrial mucosa measured by ultrasonography was 3.9 mm. Amenorrhea incidence was 93.3 and 91.6% at the 3rd and 6th month of therapy, respectively. No bleeding occurred in more than 80% of women. The results show that a low dose of oral progesterone (100 mg/day), given during 25 days, efficiently protects the endometrium by fully inhibiting mitoses and induces amenorrhea in the majority of postmenopausal women, allowing better compliance to long-term therapy.