Essential oils inhibit the bovine respiratory pathogens Mannheimia haemolytica, Pasteurella multocida and Histophilus somni and have limited effects on commensal bacteria and turbinate cells in vitro.

AIMS: The objective of this study was to determine antimicrobial activities of essential oils (EOs) against bovine respiratory disease (BRD) pathogens and nasopharyngeal commensal bacteria, as well as cytotoxicity in bovine turbinate (BT) cells in vitro. METHODS AND RESULTS: The chemical composition of 16 EOs was determined using gas chromatography-mass spectrometry. All EOs were first evaluated for growth inhibition of a single BRD pathogen Mannheimia haemolytica serotype 1 strain (L024A). The most inhibitory EOs (n = 6) were then tested for antimicrobial activity against multidrug-resistant strains of M. haemolytica (serotypes 1, 2 and 6); the BRD pathogens Pasteurella multocida and Histophilus somni, as well as commensal bacteria that were isolated from the nasopharynx of feedlot cattle. The cytotoxicity of 10 EOs was also evaluated using a BT cell line. The EOs ajowan, thyme and fennel most effectively inhibited all BRD pathogens tested including multidrug-resistant strains with minimum inhibitory concentrations (MIC) of ≤0·025% (volume/volume, v/v). For these EOs, the MIC was 2-32 fold greater against commensal bacteria, compared to BRD-associated pathogens. No cytotoxic effects of EOs against BT cells were observed within the tested range of concentrations (0·0125-0·4%, v/v). CONCLUSIONS: The EOs ajowan, thyme and fennel inhibited M. haemolytica, P. multocida and H. somni at a concentration of 0·025% and had minimal antimicrobial activity against nasopharyngeal commensal bacteria and cytotoxicity against BT cells. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated that EOs may have potential for intra-nasal administration to mitigate bovine respiratory pathogens in feedlot cattle.

Suppression of tumor-derived Semaphorin 7A and genetic ablation of host-derived Semaphorin 7A impairs tumor progression in a murine model of advanced breast carcinoma.

Solid tumors can generate a plethora of neurogenesis-related molecules that enhance their growth and metastasis. Among them, we have identified axonal guidance molecule Semaphorin 7A (SEMA7A) in breast cancer. The goal of this study was to determine the therapeutic effect of suppressing SEMA7A levels in the 4T1 murine model of advanced breast carcinoma. We used anti-SEMA7A short hairpin RNA (shRNA) to gene silence SEMA7A in 4T1 mammary tumor cells. When implanted into the mammary fat pads of syngeneic mice, SEMA7A shRNA-expressing 4T1 tumors exhibited decreased growth rates, deferred metastasis and reduced mortality. In vitro, SEMA7A shRNA-expressing 4T1 cells had weakened proliferative, migratory and invasive abilities, and decreased levels of mesenchymal factors. Atomic force microscopy studies showed that SEMA7A shRNA-expressing 4T1 cells had an increase in cell stiffness that corresponded with their decreased malignant potential. Genetic ablation of host-derived SEMA7A further enhanced the antitumor effects of SEMA7A shRNA gene silencing in 4T1 cells. Our preclinical findings demonstrate a critical role for SEMA7A in mediating mammary tumor progression.

A vapour phase assay for evaluating the antimicrobial activities of essential oils against bovine respiratory bacterial pathogens.

The objectives of this study were to develop a new assay for the evaluation of the antimicrobial activities of essential oils (EOs) in vapour phase and to demonstrate the antimicrobial activities of commercial EOs against BRPs. To achieve the first objective, a microtube cap containing 100 µl of EO was embedded in an agar plate. An agar plug (diameter 13 mm) inoculated with a bacterial suspension containing108  CFU per ml was then placed over the cap and incubated at 37°C for 24 h. Subsequently, bacteria were recovered from the agar plug by immersion in 5 ml of broth for 10 min, followed by vortexing for 30 s, and the broths were then plated for enumeration. To demonstrate the usefulness of the assay, nine commercial EOs derived from the following specific plants: ajowan, carrot seed, cinnamon leaf, citronella, fennel, ginger grass, lavender, rosemary and thyme were first evaluated for their vapour phase antimicrobial activities against Mannheimia haemolytica serotype 1. Selected EOs were further tested against Pasteurella multocida and Histophilus somni. The EOs of ajowan, thyme and cinnamon leaf completely or partially inhibited BRPs growth. This new assay provided reproducible results on the vapour phase antimicrobial activities of EOs against BRPs. These results support further study of EOs as a potential mitigation strategy against BRPs. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we present a new vapour phase assay for evaluating the antimicrobial activities of essential oils (EO) against bovine respiratory pathogens (BRPs). Using this assay, we identified EOs, such as ajowan, thyme and cinnamon leaf, that can effectively inhibit growth of the BRPs Mannheimia haemolytica serotype 1, Pasteurella multocida and Histophilus somni. This is the first study to demonstrate the vapour phase antimicrobial activity of EOs against BRPs.

Probiotic bacteria inhibit the bovine respiratory pathogen Mannheimia haemolytica serotype 1 in vitro.

This study evaluated the potential of probiotic bacteria to inhibit growth and cell adhesion of the bovine respiratory pathogen Mannheimia haemoltyica serotype 1. The inhibitory effects of nine probiotic strains (Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus helveticus, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactococcus lactis, Streptococcus thermophilus and two Paenibacillus polymyxa strains) against M. haemolytica were evaluated using a spot-on-lawn method. Probiotic strains were then tested for their adherence to bovine bronchial epithelial (BBE) cells and the ability to displace and compete against M. haemolytica on BBE. Except for S. thermophilus, all probiotic strains inhibited the growth of M. haemolytica, with zones of inhibition ranging between 12 and 19 mm. Lactobacillus strains and Lactococcus lactis displayed greater (P < 0·05) BBE adhesion compared with M. heamolytica (8·3%) and other probiotics (<2·2%). Strains of P. polymyxa and L. acidophilus caused the greatest reduction in M. haemolytica adherence, through both displacement and competition, compared with other probiotics. The results of this study suggest that probiotics may have the potential to colonize the bovine respiratory tract, and exert antagonistic effects against M. haemolytica serotype 1. SIGNIFICANCE AND IMPACT OF THE STUDY: A common method to control bovine respiratory disease (BRD) in feedlots is through mass medication with antibiotics upon cattle entry (i.e. metaphylaxis). Increasingly, antimicrobial resistance in BRD bacterial pathogens has been observed in feedlots, which may have important implications for cattle health. In this study, probiotic strains were shown to adhere to bovine respiratory cells and inhibit the BRD pathogen M. haemolytica serotype 1 through competition and displacement. Probiotics may therefore offer a mitigation strategy to reduce BRD bacterial pathogens, in place of metaphylactic antimicrobials.

Effects of dietary sulfur concentration and forage-to-concentrate ratio on ruminal fermentation, sulfur metabolism, and short-chain fatty acid absorption in beef heifers.

This study evaluated the effects of dietary S concentration and forage-to-concentrate ratio (F:C) on ruminal fermentation, S metabolism, and short-chain fatty acid (SCFA) absorption in beef heifers. Sixteen ruminally cannulated heifers (initial BW 628 ± 48 kg) were used in a randomized complete block design with a 2 × 2 factorial treatment arrangement. The main factors included F:C (4% forage vs. 51% forage, DM basis) and the S concentration, which was modified using differing sources of wheat dried distillers grains with solubles (DDGS) to achieve low- and high-S diets (LS = 0.30% vs. HS = 0.67% S on a DM basis). Elemental S was also added to increase the S content for the HS diets. Serum sulfate concentration from blood, sulfide (S(2-)), and SCFA concentrations from ruminal fluid, hydrogen sulfide (H2S) concentration from the ruminal gas cap, and urinary sulfate concentration were determined. Continuous rumen pH and SCFA (acetate, butyrate, and propionate) absorption were measured. There were no interactions between S concentration and F:C. The F:C did not affect DMI (P = 0.26) or ruminal S metabolite concentrations (P ≥ 0.19), but ruminal pH was lower (P < 0.01) and SCFA absorption was greater (P < 0.01) for low F:C diets. Heifers fed HS diets had less DMI (P < 0.01) but greater ruminal pH (P < 0.01), greater concentrations of ruminal H2S (P < 0.01) and serum sulfate (P < 0.01), and greater urinary sulfate concentration (P < 0.01) and output (P < 0.01) relative to heifers fed LS diets. Ruminal H2S was positively correlated with serum sulfate (r = 0.89; P < 0.01). Ruminal acetate concentration was not affected (P = 0.26) by dietary S concentration. Heifers fed the HS diet had lower (P = 0.01) ruminal propionate concentration and tended to have lower (P = 0.06) butyrate concentration than heifers fed the LS diet. Ruminal acetate was greater (P = 0.01) and butyrate was less (P < 0.01) with the high F:C diet than the low F:C diet. Both HS (P = 0.06) and low F:C (P = 0.07) diets tended to reduce urine output. Feeding HS diets reduced SCFA absorption (P < 0.05). In summary, S metabolism in beef heifers was not influenced by the F:C, but HS reduced DMI, inhibited SCFA absorption, and increased urinary S excretion.

Understanding the role of sulfur-thiamine interaction in the pathogenesis of sulfur-induced polioencephalomalacia in beef cattle.

This study examined the role of sulfur (S) in the pathogenesis of S-induced polioencephalomalacia (PEM) in beef cattle in the context of thiamine status and metabolism. Thiamine, thiamine monophosphate (TMP) and thiamine pyrophosphate (TPP) status in rumen fluid, blood and brain tissue were determined in beef heifers fed 2 levels of S [low S (LS) vs. high S (HS)] at 2 forage-to-concentrate ratios (F:C). High S diet did not affect ruminal and blood thiamine status. Interestingly, however, HS diet showed increased brain thiamine levels. No gross or histopathological changes indicative of PEM were detected in the brains of the heifers. Of note, during the course of the present study, we documented an outbreak of S-induced PEM in commercial feedlot steers. Brain thiamine variables in experimental animals fed HS diet were then contrasted with brain thiamine status in PEM affected feedlot steers. Interestingly, in clinically normal animals, exposure to HS diet resulted in increased levels of both TMP and TPP in the brain tissue, in comparison to animals fed LS diet. In contrast, the PEM affected brains showed overall lower levels of thiamine phosphates. It is noteworthy that TPP levels were 36.5% lower, despite 4.9-fold higher free thiamine in PEM brains compared to normal brains. Our results indicate that high dietary S may increase the metabolic demand for TPP, and that animals incapable of maintaining requisite levels of brain TPP are at high risk to develop fulminant cerebrocortical necrosis.

Screening for fetal spina bifida at the 11-13-week scan using three anatomical features of the posterior brain.

OBJECTIVE: To evaluate the contribution of examination of specific anatomical features of the fetal posterior brain on mid-sagittal first-trimester ultrasound examination to the early detection of open spina bifida. METHODS: Four independent observers reviewed a series of 260 mid-sagittal first-trimester ultrasound images from 52 cases of open spina bifida and 208 normal fetuses. The following analysis was performed by each reviewer for each image: Herman score calculation, intracranial translucency score (CFEF-IT) calculation and determination of presence or absence of three anatomical criteria: intracranial translucency (IT), caudal displacement of the brainstem and cisterna magna. The sensitivity and the false-positive rate for spina bifida detection were calculated for each of the latter three criteria. A secondary analysis was performed on the subset of images achieving a Herman score ≥ 7. RESULTS: The highest detection rate for spina bifida was achieved by non-visualization of the cisterna magna, with associated sensitivity of 50-73% and 39-76%, respectively, for all images and for the subset of images achieving a Herman score ≥ 7. Posterior shift of the brainstem achieved the highest detection rate (86%), but for a single reviewer only. The level of variation in performance between observers was also greatest for this sign. Absence of IT was associated with a lower detection rate for all observers. Overall, an abnormal posterior brain presenting at least one of these three criteria was associated with a detection rate ranging from 50 to 90%. CONCLUSION: In the detection of spina bifida, non-visualization of the cisterna magna achieved the best screening performance. Both non-visualization of the IT and posterior shift of the brainstem were associated with acceptable but lower detection rates. A prospective evaluation of changes in the posterior brain is needed to allow assessment of the most pertinent criteria for first-trimester screening for spina bifida.

Visualization of intracranial translucency at the 11-13-week scan is improved after specific training.

OBJECTIVE: To evaluate the ability to confidently identify intracranial translucency (IT) in a clinical practice and following specific training of 10 operators. METHODS: Two experienced observers reviewed 11-13-week nuchal translucency (NT) images for IT visibility in (1) a series of 50 randomly selected images obtained by 10 skilled operators certified by the Collège Français d'Echographie Foetale (CFEF) (retrospective analysis) and (2) a series of 315 images obtained by 10 different operators following specific training for IT visualization (prospective analysis). We calculated proportions of images for which IT was deemed visible and the agreement between the two observers. Data were also stratified by Herman and CFEF quality-score intervals. RESULTS: In the retrospective analysis, IT was visualized by both reviewers in 52% of images, with a moderate level of agreement (κ = 0.63). The rate of IT visualization by both reviewers increased very slightly to 56-58% when only considering images with the best NT quality-control scores. Following specific training of the operators the proportion of images for which both reviewers could identify the fourth ventricle increased to 85%, but the level of agreement remained moderate (κ = 0.66). When considering images with the best NT quality-control scores, IT visualization by both reviewers increased to 91-92%. CONCLUSIONS: In a clinical practice that focuses on NT measurement IT cannot be visualized in a substantial proportion of the images obtained, which limits the utility of this approach for the early prenatal diagnosis of open spina bifida. However, the ability to identify the fourth ventricle significantly increases following specific training.

Isolated hyperechoic fetal colon before 36 weeks' gestation reveals cystinuria.

OBJECTIVES: To determine whether there is an association between the fetal ultrasound finding of hyperechoic colon and the gestational age at which it presents and cystinuria. METHODS: A prospective national survey was performed in France including all observations of isolated fetal hyperechoic colon detected at routine second- and third-trimester ultrasound over a 2-year period. Collected images were reviewed by experts. Colon was defined as being hyperechoic when its echogenicity was at least equal to that of the iliac bone. It was diagnosed when large tubular echogenic portions of the colon, without a focal mass and without posterior acoustic shadows, were observed at the periphery of the abdomen. Urinary amino acid analysis was performed after birth in the cases identified to test for cystinuria. RESULTS: Nineteen fetuses with ultrasound findings of hyperechoic colon were included, and the mothers of 16 of these agreed to participate in the study. In eight of nine cases of hyperechoic colon observed before 36 weeks' gestation cystinuria was confirmed at birth. In the seven remaining cases, observed after 36 weeks, none was found to have cystinuria and all had normal images at previous routine ultrasound scans at 22 and 33 weeks. When present, no difference in the sonographic appearance of hyperechoic colon was noted between the two groups. In the cystinuria-affected cases, the length of the hyperechoic mass appeared to increase with gestational age. CONCLUSIONS: In our experience, the presence of a hyperechoic colon at routine ultrasound scan before 36 weeks' gestation should prompt screening for cystinuria at birth, while later observation (> 36 weeks) of this finding does not appear to be related to any disease.

Development of near infrared sensors: detection of influential factors by the AComDim method.

The development of near infrared (NIR) sensors has to go through different steps of testing. Once a prototype is ready to be used, it is necessary to evaluate and optimize the experimental conditions and the data collection, in terms of accuracy, repeatability, reproducibility and speed. This paper studies the effects of controllable experimental factors on the quality of the spectral response, to determine the influence of each instrumental parameter and to improve the predictions obtained from the collected data. The AComDim method, based on the multi-block analysis of ANOVA matrices, was used here to evaluate the impact of experimental factors on the responses from the different sensors tested.

Small cell carcinoma of the ovary successfully treated with radiotherapy only after surgery: case report.

UNLABELLED: Small cell ovarian tumors are rare and highly malignant, occurring mainly in young patients. Early mortality is high due to the lack of an effective treatment. The first adjuvant therapy is usually chemotherapy. CASE: During laparotomy for renal transplant in a 17-year-old girl, the right ovary exhibited a suspicious mass, whose pathological diagnosis was Stage 1A small cell ovarian tumor. Prognosis was poor (young age, hypercalcemia, tumor >10 cm, and presence of large cells). Since chemotherapy is contraindicated for dialysed patients, only radiotherapy was given. The patient is still alive and disease-free ten years after diagnosis. CONCLUSION: This is the first case with a poor prognosis reported in the literature that has been successfully cured by surgery plus adjuvant radiotherapy only.

Tumor parameters, clinical and pathological responses, medical management, and survival through time on 710 operable breast cancers.

The aim of the current study is an analysis of tumor parameters, clinical and pathological responses, medical management, and survival on 710 operable breast cancer patients who received neoadjuvant chemotherapy from 1982 to 2004 and were grouped into four successive periods according to diagnosis date: (1) 1982-1989; (2) 1990-1994; (3) 1995-1999; and (4) 2000-2004. Patients were treated by different neoadjuvant chemotherapies combinations: AVCF/M, TNCF, NEM, NET, TAXOTERE, FEC 50, 75, 100, FAC 50, and TAXOTERE-TNCF, mainly in successive prospective phase II trials. They received a median number of six cycles (range, 1-9). After primary chemotherapy, patients underwent a surgery and a radiotherapy. In case of significant residual disease, some patients received additional courses of chemotherapy. In addition, menopausal patients with hormonal receptor-positive tumors received tamoxifen for 5 yr. Clinical factors had some remarkable variations with time. The median age of the patients was 49.5 yr (range, 26-81). The size of the tumor was significantly greater from 1995; conversely, clinical lymph-node involvement was lower in period 4 than in the first period. The percentage of invasive ductal carcinoma and of SBR III tumors increased about 20% from 1982-1989 to 2000-2004. The number of positive hormonal receptors increased from 38.3% in period 1 to 74% in period 4. The clinical response rate improved recently from before 1990. The pathological response rate was greater in periods 2 and 3 than in periods 1 and 4. An adjuvant hormonotherapy became progressively more frequently given (44.7 for period 1 and 73.3% for period 4). Finally, no significant difference was found when we compared overall and disease-free survival through the four periods. It appears that the progressive increase of tumor burden was compensated by more effective treatments.

Is Nottingham prognostic index useful after induction chemotherapy in operable breast cancer?

The Nottingham prognostic index (NPI), based on tumour size in breast, node involvement and Scarff-Bloom-Richardson (SBR) grading, has been shown to constitute a definitive prognostic factor of primary operable breast cancer in the adjuvant setting. We performed a retrospective study to evaluate the prognostic value of this index in 163 patients after neoadjuvant chemotherapy. Secondly, we examined the influence on survival of a revised NPI, only based on residual tumour size in breast and SBR grading in 228 patients, and consequently called breast grading index (BGI). The prognostic value of these two indices was also evaluated by replacing the SBR grade with the MSBR grade, a French modified SBR grading; the modified NPI (MNPI) and modified BGI (MBGI) were, respectively, obtained in 153 and 222 patients. At a median follow-up of 9.3 years, survival was significantly related to these four indices (P<0.001). Multivariate analysis revealed that MBGI was the only one which retained a prognostic influence on disease-free survival (P<0.02). In conclusion, the 'amount' of residual tumour in breast and/or nodes, as defined by NPI and revised indices, confers a determinant prognosis after neoadjuvant chemotherapy, inviting an alternative postsurgical treatment for a subgroup of patients with a decreased survival.

Neoadjuvant docetaxel for operable breast cancer induces a high pathological response and breast-conservation rate.

Docetaxel (Taxotere), alone or in combination with other anticancer agents, has proven efficacy in the first- and second-line treatment of metastatic breast cancer. This phase II study investigated the efficacy and tolerability of docetaxel as neoadjuvant chemotherapy in women with stage II-III primary operable breast cancer. Patients (n=88) were treated with six cycles of docetaxel at 100 mg m(-2) every 21 days, followed by definitive surgery and radiotherapy. After six cycles of docetaxel, the overall clinical response rate was 68.4% (CI 95%: 58.1-78.7%), including 19.0% complete remissions. Breast conservation was achieved in 72.4% of patients. A high pathological complete response (pCR) rate in breast was confirmed in 15 patients (19.8% (CI 95%: 10.8-28.8%)) on Chevallier's classification restricted to breast and in 27 patients (35.5% (CI 95%: 24.7-46.3%)) on Sataloff's classification. After a median follow-up of 30.8 months, 19 recurrences were documented with a median time to first recurrence of 17.3 months. Patients with stage III tumours had more recurrences than patients with stage II tumours (P=0.02). The principal toxicity of docetaxel is myelosuppression and 70.5% of patients developed grade III or IV neutropenia with 13.6% developing neutropenic sepsis. There was no case of severe cardiac toxicity, thrombocytopenia or any other serious adverse events. In conclusion, neoadjuvant docetaxel induces a high pCR and breast-conservation rate. Docetaxel monotherapy is a highly effective regimen that merits formal comparison with currently used combination regimens in a randomised phase III study.

Prognostic significance of a complete pathological response after induction chemotherapy in operable breast cancer.

Only a few papers have been published concerning the incidence and outcome of patients with a pathological complete response after cytotoxic treatment in breast cancer. The purpose of this retrospective study was to assess the outcome of patients found to have a pathological complete response in both the breast and axillary lymph nodes after neoadjuvant chemotherapy for operable breast cancer. Our goal was also to determine whether the residual pathological size of the tumour in breast could be correlated with pathological node status. Between 1982 and 2000, 451 consecutive patients were registered into five prospective phase II trials. After six cycles, 396 patients underwent surgery with axillary dissection for 277 patients (69.9%). Pathological response was evaluated according to the Chevallier's classification. At a median follow-up of 8 years, survival was analysed as a function of pathological response. A pathological complete response rate was obtained in 60 patients (15.2%) after induction chemotherapy. Breast tumour persistence was significantly related to positive axillary nodes (P=5.10(-6)). At 15 years, overall survival and disease-free survival rates were significantly higher in the group who had a pathological complete response than in the group who had less than a pathological complete response (P=0.047 and P=0.024, respectively). In the absence of pathological complete response and furthermore when there is a notable remaining pathological disease, axillary dissection is still important to determine a major prognostic factor and subsequently, a second non cross resistant adjuvant regimen or high dose chemotherapy could lead to a survival benefit.

Screening for microdeletions on the long arm of chromosome Y in 53 infertile men.

About 30% of couple infertilities are of male origin. They appear in some cases de novo and are considered idiopathic. The aim of our work was to evaluate, in these cases, the prevalence of microdeletions of the long arm of chromosome Y, within the AZF a, b and c regions using molecular biology techniques. Men with azoospermia or oligozoospermia resulting from hereditary, endocrine or obstructive causes, or with a constitutional cytogenetic abnormality were excluded. Fifty-three infertile men with azoospermia or oligozoospermia, as determined by a spermiogram, were studied. Of these, 34 were idiopathic and 7 exhibited a past history of genital infection or biological abnormalities, suggesting partial obstruction of the genito-urinary tract. A further 8 men had a varicocele and 11 cases with a history of cryptorchidism were also studied. Peripheral blood DNA was extracted from each patient, then amplified by multiplex PCR with STS genomic markers from the three Y chromosome AZF zones. PCR products were then analysed on agarose gels. In view of the difficulty of confirming the absence of a signal in molecular biology, each case suspected of having a deletion was checked by multiplex PCR through coamplification with the SRY marker. Five men with microdeletions of the long arm of the Y chromosome were diagnosed among the 53 patients. All of them included the AZFc zone and the intragenic DAZ gene markers. Furthermore, a larger Y chromosome deletion encompassing the 3 AZF zones was diagnosed, and confirmed by cytogenetic analysis. All Y chromosome microdeletions were observed in the 34 truly idiopathic azoospermia/oligozoospermia cases, corresponding to a proportion of 14.7% (or 9.4% considering the whole population of 53 infertile men). The relatively high proportion of microdeletions found in our series suggests the need for strict patient selection to avoid unnecessary screening for long arm Y chromosome microdeletions.

Relationship between circadian rhythm of vinorelbine toxicity and efficacy in P388-bearing mice.

The relevance of chronopharmacology for improving tolerability and antitumor efficacy of the antimitotic drug vinorelbine was investigated in female B6D2F1 mice standardized with 12 h of light and 12 h of darkness. A single i.v. vinorelbine dose (26 mg/kg) was given to 279 mice at 7, 11, 19, or 23 hours after light onset (HALO). Bone marrow necrosis and leukopenia were nearly twice as large in the mice injected at 7 HALO as compared with those treated at 19 HALO (ANOVA: p <.001 and p = 0.004, respectively). The relevance of vinorelbine dosing time for antitumor efficacy was assessed in 672 P388 leukemia-bearing mice. Vinorelbine was injected as a single dose (20, 24, 26, or 30 mg/kg) or weekly (20, 24, 26, or 28 mg/kg/injection x 3) at one of six circadian times, 4 h apart. A significant correlation between single dose and median survival time was limited to vinorelbine administration at 19 or 23 HALO. An increase in the vinorelbine weekly dose shortened median survival time in the mice treated at 7 HALO (20 mg/kg: 29 days; 24 mg/kg: 17 days; and 26 mg/kg: 6 days) but significantly improved it in those treated at 19 HALO (20 mg/kg: 28.5 days; 24 mg/kg: 32 days; and 26 mg/kg: 36 days). The study demonstrates the circadian rhythm dependence of maximum tolerated dose and the need to deliver maximum tolerated dose at the least toxic time to achieve survival improvement through chronotherapy. This may be obtained with an evening administration of vinorelbine in cancer patients.

[Search for microdeletions in the long arm of chromosome Y in 48 infertile men]. / Recherche de microdélétions du bras long du chromosome Y chez 48 hommes infertiles.

About 30% of infertilities are from male origin. They appear in some cases de novo and considered idiopathic. The aim of our work is to evaluate, in these cases, the Y chromosome long arm microdeletion prevalence within the AZF a, b and c regions by molecular biology technics. Were excluded from our study, azoo-oligospermia from hereditary, endocrine, obstructive origins or with a constitutional cytogenetic abnormality. 48 infertile men with a spermogram-proven azoo-oligospermia were studied. Among them, 30 were idiopathics, 8 out of them exhibited a genital infection past history or biological abnormalities suggesting partial obtruction of the genito-urinary tractus. 8 cases of varicocela and 10 of cryptorchidia were also studied. Peripheral blood DNA was extracted from each patient, then amplified by multiplex PCR with STS genomic markers from the 3 Y chromosome AZF zones. PCR products were then analysed on agarose gels. Considering the difficulty to affirm the absence of a signal in molecular biology, each suspicion of deletion was checked by multiplex PCR complication with the SRY marker. 5 Y chromosome long arm microdeletions were diagnosed among our 48 patients. All of them included the AZFc zone and the intragenic DAZ gene markers. Moreover a larger Y chromosome deletion encompassing the 3 AZF zones was diagnosed, and confirmed by the cytogenetic analysis. All the Y chromosome microdeletions were observed in the 22 truly idiopathic azoo/oligospermia, corresponding to a proportion of 22.7% which falls to 10.4% considering the whole population of 48 studied people (closer to the published data). The relatively high proportion of microdeletions found in our series, underlines the need of a strict patient selection to avoid unnecessary search for long arm Y chromosome microdeletions.

[Pseudo-tumor of Castleman: particular aspects of thoracic localization. Two case reports]. / Pseudo-tumeur de Castleman. Aspects particuliers de la localisation thoracique. A propos de deux observations.

The pseudo-tumours of Castleman, irrespective of whether their histological type is plasmocytic or hyalino-vascular, are most often found in the mediastino-pulmonary area. 2 rare aspects of their thoracic localisation are reported with the occurrence of a pleural effusion and the localisation to the chest wall itself.

Opportunistic agents in bronchoalveolar lavage in 99 HIV seropositive patients.

During a ten month period, 117 fibreoptic bronchoscopies and bronchoalveolar lavages (BAL) were performed in human immunodeficiency virus (HIV) infected patients suspected of having opportunistic pulmonary infections. The BAL were classified into 3 groups, according to clinical manifestations related to HIV infection at the time of fibreoptic bronchoscopy: pre-acquired immunodeficiency syndrome (AIDS) (n = 54), AIDS with Kaposi's sarcoma (n = 37), AIDS without Kaposi's sarcoma (n = 26). On chest X-ray, diffuse infiltrates were most common (54%), followed by normal X-rays (24%) and localized infiltrates (18%). Amongst the 117 BAL, 68 (58%) yielded at least one opportunistic agent. In 28 BAL performed for pulmonary signs or unexplained fever with normal chest X-rays, one or several opportunistic agents were isolated in 17 samples of BAL fluid. The most frequently identified opportunistic agents were Pneumocystis carinii (in 38% of BAL) and cytomegalovirus (35%); these were associated in 17% of BAL. There was no statistically significant difference in opportunistic agents among the 3 groups of BAL (pre-AIDS, AIDS with Kaposi's sarcoma, AIDS without Kaposi's sarcoma). In particular, cytomegalovirus was found in BAL with the same frequency in these 3 groups.