Validation of the 'EPICES' social deprivation score in a population of women who have just given birth: a French cross-sectional study.

OBJECTIVES: To assess the diagnostic performance of the EPICES score for identifying social deprivation during pregnancy in a population of women in the immediate postpartum period. STUDY DESIGN: This cross-sectional survey took place between 5th June and 5th August 2017, among women who had just given birth in either of the maternity units in Clermont-Ferrand, France. METHODS: A self-administered questionnaire was completed by women. The questionnaire came in two parts: the EPICES index and the criteria for social deprivation defined by French law. These criteria were chosen to define the reference standard. The women were classified into two groups, living in precarious circumstances or not, according to the criteria defined by the French law (reference standard). To determine the most relevant threshold of the EPICES score, the precision associated with the threshold (the fraction of those predicted positive who are true positives: positive predictive value) was balanced with its sensitivity. EPICES scores above the threshold were classified as deprived, those below as non-deprived. RESULTS: Of the 947 women who gave birth during the study period, 700 (73.9%) completed the self-administered questionnaire. The best trade-off between precision and sensitivity was obtained with a threshold of 22. For this threshold value, the positive predictive value was 42.3% and the sensitivity 70.3%. CONCLUSIONS: The EPICES score with a threshold validated in the population of pregnant women is a useful, rapid, and easy-to-use tool that makes it possible to identify maternal deprivation at an individual level.

Improving image quality of mid-trimester fetal sonography in obese women: role of ultrasound propagation velocity.

OBJECTIVE: The quality of ultrasound images is impaired in obese patients. All ultrasound scanners are calibrated for an ultrasound propagation velocity of 1540 m/s, but the propagation in fatty tissue is slower (in the order of 1450 m/s). The main objective of this study was to evaluate the quality of images obtained with different ultrasound propagation velocity settings during the mid-trimester fetal ultrasound examination in obese patients. METHODS: This was a cross-sectional study using image sets of four recommended scanning planes collected from 32 obese pregnant women during their mid-trimester fetal scan. Each image set comprised three images obtained successively at three different propagation velocity settings (1540 m/s, 1480 m/s and 1420 m/s). A panel of 114 experts assessed the quality of 100 image sets, grading them from A (most acceptable) to C (least acceptable). Scanning-plane-specific indicators of adiposity (fatty layer thickness, probe-to-organ distance) were analyzed for each scanning plane. RESULTS: The experts had a mean of 18.1 ± 10.2 years of experience. The grade distribution (A, B, C) differed significantly (P < 0.0001) between the three propagation velocity settings tested; at the lower speed of 1480 m/s, images were most often graded A, while at the conventional speed of 1540 m/s, they were most often graded C. Regardless of the scanning plane, the thicker the fatty layer of the abdominal wall in a given plane, the lower the preferred speed (P < 0.0001). CONCLUSION: The construction of images taking into account ultrasound propagation velocities lower than 1540 m/s can improve significantly the quality of images obtained during mid-trimester fetal ultrasonography in obese women. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

[Psychiatrists' decision making and monitoring of antipsychotic prescription for elderly schizophrenia patients]. / Prescription et surveillance d'antipsychotiques chez les patients âgés souffrant de schizophrénie: pratiques des psychiatres et leurs déterminants.

OBJECTIVE: Advancing age entails specific treatment modalities for patients with schizophrenia. The choice of appropriate antipsychotic therapy (AP) and the monitoring of treatment is a major challenge. However, little is known about the real-world prescribing practices of psychiatrists for elderly schizophrenia patients. The aim of this study was to assess prescribing practices and treatment monitoring in elderly schizophrenia patients and whether socio-professional psychiatrists' characteristics are related to their practices. METHODS: We contacted by mail 190 psychiatrists to take part in an observational survey of their AP prescribing practices for elderly (aged over 65) schizophrenia patients. RESULTS: The response rate was 44.2%, and of the psychiatrists who replied 75% were treating elderly schizophrenia patients. A second-generation AP (SGAP) was prescribed as first-line of treatment by 87.7% of the psychiatrists. The most frequently used SGAPs were risperidone and olanzapine (respectively preferred by 54.4% and 19.3% of the psychiatrists taking part). At the beginning of treatment, 91.1% of the psychiatrists prescribed a lower dose than for middle-aged patients. Of the psychiatrists taking part, 64.9% prescribed monotherapy; and among these psychiatrists, 65% cited insufficient control of the disease as the reason for their choice, while 48.7% of those who elected not to prescribe combined AP did so in order to limit the side-effects. Of the psychiatrists taking part, 54.4% prescribed long-acting injectable AP (LAAP); better therapeutic compliance and alliance was the main argument in the choice of LAAP given by the psychiatrists taking part who prescribed the drug, whereas the absence of indications and problems of tolerance were arguments against for those who did not. "Personal experience" emerged as the governing factor in the choice of AP. The AP side-effect profile was the main criterion of choice of the AP agent for 3.5% of the psychiatrists taking part, and the most frequently chosen secondary criterion (29.8%). Monitoring of treatment was partly performed according to professional recommendations: pre-treatment and post-prescription assessments of waist circumference and ophthalmological monitoring were very infrequent (8.8 to 18.5%) as were pre-treatment and early post-prescription assessments of prolactinaemia (14.8 to 20.4%); long-term cardiac monitoring was infrequent (43.9%). The psychiatrists taking part whose first-line drug was SGAP were more familiar with professional recommendations than those who prescribed first generation antipsychotic (FGA) drugs (72% as against 14.3%, P=0.006). Of the psychiatrists taking part in the study, 64.9% reported they commonly use professional recommendations. Psychiatrists who declared they commonly use professional recommendations measured pulse rate and blood pressure significantly more often over the long-term than those who did not (74.3% as against 41.2%, P=0.0315). They also measured waist circumference over the long-term significantly more often than psychiatrists who did not commonly use professional recommendations (22.9% as against 0%, P=0.0420). Psychiatrists treating more than ten of these patients yearly measured significantly more often over the long-term pulse rate and blood pressure than those treating fewer patients (80% as against 50%, P=0.0399). Over the long-term monitoring, psychiatrists with a larger number of elderly schizophrenia patients in their care also performed more often fasting blood glucose test, lipid profile and referral for cardiac consultation with ECG (respectively, 95.5% as against 70.8%, P=0.0489; 90.9% as against 58.3%, P=0.0182; 81.8% as against 29.2%, P<0.0001). CONCLUSIONS: The results of this survey need to be confirmed in a larger population sample. The antipsychotic prescribing practices were broadly in agreement with current recommendations except for the tolerance profile which was not the first element taken into account in the choice of the AP agent. Some clinical and paraclinical medical examinations were carried out infrequently, in particular cardiac monitoring over the long-term, which is essential in this elderly patient population. One important element to emerge from our results was that common use of professional recommendations is associated with better monitoring.

[Health-related quality of life evaluation of elderly aged 65 years and over living at home]. / Évaluation de la qualité de vie liée à la santé de sujets âgés de 65ans et plus vivant à domicile en région Auvergne.

BACKGROUND: To assess health-related quality of life in French adults aged 65 years and over, living at home, with a specific self-administered questionnaire, the LEIPAD, cross-culturally adapted in French. METHODS: Elderly completed socio-demographic and medical questionnaires, a questionnaire about negative life events during the last 12 months and the LEIPAD. RESULTS: Data of 195 subjects (mean age: 72.6 years, men: 56.5%) were analyzed. The response rates to the LEIPAD scales were superior to 90%. Elderly reported on the whole a good health-related quality of life. Age had a negative effect on quality on life, which deteriorates over years. Age was correlated to the scales "Physical function", "Self-care", "Cognitive functioning" and "Sexual functioning". Elderly hospitalized in the last year had worse quality of life with a significant difference for "Physical function" scale. The number of health problems was positively correlated to "Physical function" scale. Elderly declaring at least one health problem had worse quality of life for this scale. Problems in couple, materials and financial problems had also negative effects on health-related quality of life. CONCLUSION: Our study highlights a good health-related quality of life for the majority of these adults aged 65 years and over, as well as the negative effect of age, health, couple, materials and financial problems on their quality of life.

Shift of the 2009-2011 measles outbreak from children to adults: an observational review at the University Hospital of Clermont-Ferrand, France.

In 2009-2011, 113 adult in- and outpatients with measles were referred to the University Hospital of Clermont-Ferrand (centre of France): 71 (62.8 %) needed hospitalisation, 31 had pneumonia, 29 diarrhoea, 47 liver enzymes elevation, 38 thrombopaenia, one encephalitis and there were no deaths. Nineteen cases occurred among healthcare workers and five of them were hospital-acquired. There were 92 unvaccinated patients. The 2011 peak of that measles re-emerging epidemic occurred when non-immunised adults were affected.

Cross-cultural evaluation of the French version of the LEIPAD, a health-related quality of life instrument for use in the elderly living at home.

PURPOSE: To cross-culturally adapt a French version of the LEIPAD, a self-administered questionnaire assessing the health-related quality of life (HRQoL) in adults aged 65 years and over living at home, and to evaluate its psychometric properties. METHODS: After having translated LEIPAD in accordance with guidelines, we studied psychometric properties: reliability and construct validity-factor analysis, relationships between items and scales, internal consistency, concurrent validity with the Medical Outcome Study Short-Form 36 and known-groups validity. RESULTS: The results obtained in a sample of 195 elderly from the general population showed very good acceptability, with response rates superior to 93 %. Exploratory factor analysis extracted eight factors providing a multidimensionality structure with five misclassifications of items in the seven theoretical scales. Good internal consistency (Cronbach's alpha ranging from 0.73 and 0.86) and strong test-retest reliability (ICCs higher than 0.80 for six scales and 0.70 for one) were demonstrated. Concurrent validity with the SF-36 showed small to strong expected correlations. CONCLUSION: This first evaluation of the French version of LEIPAD's psychometric properties provides evidence in construct validity and reliability. It would allow HRQoL assessment in clinical and common practice, and investigators would be able to take part in national and international research projects.

Perceived barriers to and facilitators of physical activity in people with knee osteoarthritis: Development of the Evaluation of the Perception of Physical Activity questionnaire.

BACKGROUND: The physical activity (PA) level of individuals with knee osteoarthritis is lower than in the general population. International recommendations recommend a non-pharmacological intervention including a self-management education program, weight loss and an adapted exercise program. However, we have no scale assessing the perceived barriers to and facilitators of PA in this population. OBJECTIVE: We constructed and validated a self-administered questionnaire assessing perceived barriers to and facilitators of regular practice of PA in people with knee osteoarthritis. METHODS: Semi-structured interviews identified 24 barriers and facilitators. We developed a 24-item questionnaire, Evaluation of the Perception of Physical Activity (EPPA) that was completed by 548 individuals with knee osteoarthritis, to assess acceptability, construct validity, internal consistency and convergent validity. Participants also completed the Knee Osteoarthritis Fears and Beliefs Questionnaire (KOFBeQ), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and International Physical Activity Questionnaire (IPAQ). Reliability and sensitivity to change were evaluated in a second group of 168 people with knee osteoarthritis at a 3-week spa therapy resort. RESULTS: Factorial analysis identified 17 items grouped into 4 subscales (Barriers, Facilitators, Motivation and Beliefs). The internal consistency was good for Barriers, Facilitators and Motivation subscales (Cronbach α>0.70) and intermediate for the Beliefs subscale (Cronbach α=0.64). The EPPA subscale scores were significantly correlated with KOFBeQ and WOMAC scores but not associated with IPAQ physical activity level. Reliability was good for all subscales, with intraclass correlation coefficients>0.60. A sensitivity to change was found for only the Beliefs subscale, with a moderate effect size. CONCLUSIONS: The EPPA questionnaire has good psychometric properties and can help guide the management of knee osteoarthritis. It can be used in research for evaluating the perception of physical activity.

[Quality of life in multiple sclerosis]. / La qualité de vie des patients souffrant de sclérose en plaques.

Multiple sclerosis is responsible for impairment and disability, which play a major role in the personal burden of the disease. Health-related quality of life (HRQoL) has been intensively studied in this medical condition, more intensively than in other chronic neurological disorders, perhaps because of the limitations of the conventional disability instruments, which seem less sensitive to change. Moreover, HRQoL measurements can summarize all sources of patient satisfaction and dissatisfaction. Instead of relying on motor limitations, many psychological, social, and neuropsychological factors, such as cognitive impairment and fatigue, are predictors of a reduced quality of life, even in the early stages, more than conventional radiological MRI. The analysis of self-administered HRQoL questionnaires, generic or mixed (specific and generic), can help clinicians advance toward the best therapeutic approach for the patient.

Psychometric properties of the French version of the Endometriosis Health Profile-30, a health-related quality of life instrument.

INTRODUCTION: The objectives were to evaluate the acceptability, reliability and validity of the cross-cultural adaptation of the Endometriosis Health Profile-30 instrument into French. METHODS: This cross-sectional study was conducted between July and October 2015. We created an online link (REDCap platform) with the questionnaires. An endometriosis patients association spread the link on its website and with social networks. The translation and cultural adaptation of the EHP-30 was performed according to guidelines. Psychometric evaluation included data completeness, score distributions, floor and ceiling effects, factor analysis, internal consistency, item-total correlations corrected for overlap, convergent validity and test-retest reliability. RESULTS: The study included 913 women with endometriosis. In our results, data completeness was excellent. No floor effects were found and one ceiling effect was observed for the 'Infertility' scale. The highest means scores were found for 'Control and powerlessness' and 'Infertility' scales. Factor analysis confirmed the structure of the original EHP-30 questionnaire. Internal consistency was good (Cronbach's α range=0.72-0.96). The correlations of similar scale scores between EHP-30 and SF-36 were all significant (Spearman correlation coefficients ranging from -0.52 to -0.75). Test-retest reliability was good (intraclass correlation coefficients range=0.51-0.98). CONCLUSION: The French version of the EHP-30 is an acceptable, reliable and valid instrument for measuring health-related quality of life in women with endometriosis.

Optimization of alternate-strand triple helix formation at the 5"-TpA-3" and 5"-ApT-3" junctions.

Alternate-strand triple helix formation was optimized at the two junction steps, the 5"-TpA-3" and 5"-ApT-3" junctions. Footprint experiments, gel retardation assays and thermal denaturation measures on a sequence appropriately designed with two adjacent alternate-strand polypurine tracts points out that the addition of an adenine residue and the removal of one nucleotide should facilitate the crossing strands at the 5"-TpA-3" junction and at the 5"-ApT-3" junction, respectively. These results provide a 'switch code' for the construction of alternate-strand triple helix forming oligonucleotides which open new possibilities for extending the range of applications of antigene strategy.

Simultaneously monitoring DNA binding and helicase-catalyzed DNA unwinding by fluorescence polarization.

A new method for helicase-catalyzed DNA unwinding is described. This assay takes advantage of the substantial change in fluorescence polarization (FP) upon helicase binding and DNA unwinding. The low anisotropy value, due to the fast tumbling of the free oligonucleotide in solution, increases abruptly upon binding of helicase to the fluorescein-labeled oligonucleotide. The high anisotropy of the helicase- DNA complex decreases as the fluorescein-labeled oligonucleotide is released from the complex through helicase-catalyzed DNA unwinding. This FP signal can be measured in real time by fluorescent spectroscopy. This assay can simultaneously monitor DNA binding and helicase-catalyzed DNA unwinding. It can also be used to determine the polarity in DNA unwinding mediated by helicase. This FP assay should facilitate the study of the mechanism by which helicase unwinds duplex DNA, and also aid in screening for helicase inhibitors, which are of growing interest as potential anticancer agents.

Covalent binding of elliptinium acetate (NSC 264137) to nucleic acids of L1210 cells in culture.

Elliptinium acetate (9-OH-NME; Celiptium) is an antineoplastic agent currently used in the treatment of metastatic breast cancer and is known to intercalate into DNA. Previous studies have demonstrated that this molecule can be oxidized, yielding a reactive electrophilic form, which is able to bind covalently to a nucleophilic biological molecule. In this work, we evidenced a covalent binding of this drug to nucleic acids of L1210 cells in culture. A high performance liquid chromatography technique allowed us to distinguish between reversible and nonreversible interaction and to determine the binding ratio (rb) of covalently bound elliptinium versus bases of nucleic acids extracted from cells. After an 8-h incubation of L1210 cells with 0.1 microM elliptinium (the dose corresponding to the 50% inhibitory dose), we obtained 2.4 X 10(-6) and 3.4 X 10(-6) as the rb for RNA and DNA, respectively. The kinetics of binding was also studied. The dose-response relationship obtained is linear in a concentration range of 0.025 to 0.5 microM 9-OH-NME. Furthermore, we demonstrated that the covalent binding of 9-OH-NME to DNA is not repaired during a period of 40 h (during this period, the cell population has undergone two doublings). The nonhydroxylated and non-antitumoral derivative of 9-OH-NME, N2-methylellipticinium, is 20 to 30 times less active in terms of covalent binding to nucleic acids, compared to the antitumor compound 9-OH-NME. The implication of the covalent binding of 9-OH-NME is discussed with respect to its mechanism of action.

Impairment of Moloney murine leukemia virus integration in a cell line underexpressing DNA topoisomerase II.

The possible intervention of nuclear proteins as cofactors of integrase-catalyzed integration of retroviral DNA into the host cell genome is not fully understood. Among various nuclear proteins, DNA topoisomerase II appears to be a plausible candidate. This hypothesis is supported by a series of evidence, including the fact that integration is markedly affected by the topology of the target DNA and mainly occurs in transcribed regions in which topoisomerase II is preferentially located. In an attempt to confirm the validity of this hypothesis, we have comparatively investigated the early stages of a recombinant Moloney murine leukemia virus (psi neo) in two related Chinese hamster cell lines (DC3F and R/DC3F) expressing different levels of both isoforms of topoisomerase II. R/DC3F is derived from the parental cell line DC3F and displays a resistant phenotype towards the usual anticancer topoisomerase II inhibitors (actinomycin D, doxorubicin, and taxol). Results show that the early stages of the retroviral cycle are markedly impaired in cells underexpressing topoisomerase II (R/DC3F). This alteration mimics Fv-1 restriction and is characterized by about a 6-fold decrease in viral DNA synthesis and total inhibition of viral genome integration. The specific impairment of integration in R/DC3F cells compared to DC3F cells is assessed by the absence of G418-resistant colonies upon viral infection and a lack of the viral genome in cellular nuclear DNA as detected by the PCR procedure. These features are observed in relevant infecting conditions leading, in both cell lines, to the same amount of linear viral DNA and to the occurrence of two long terminal repeats containing circular DNA in the nuclear fractions.

Superoxide dismutase, catalase, and glutathione peroxidase in red blood cells from patients with malignant diseases.

Superoxide dismutase (SOD), catalase, and glutathione peroxidase activities have been determined in red blood cells isolated from patients with acute myelogenous leukemia, chronic lymphocytic leukemia, Hodgkin's disease, lymphosarcoma, and various visceral cancers. In all investigated cases, both catalase and glutathione peroxidase were found to be in normal ranges of activity. In the group of patients with visceral cancers, SOD activity was found to be normal as well. In contrast, SOD activity was found to be significantly increased in red blood cells from patients with acute myelogenous leukemia and lymphoproliferative syndromes. This increase in superoxide level was not related to either reticulocytosis or hypochromic anemia. No relationship was found between the SOD level and the stage, the extension of the disease, or the presence of an inflammatory syndrome. The highest SOD levels were observed in untreated patients or during the early time period of the treatment. SOD levels further decrease as a function of the increase in the duration of the treatment. These results suggest an abnormality in the regulation of the expression of the SOD gene in the pluripotent stem cells.

Physicochemical and pharmacological properties of the antitumor ellipticine derivative 2-(diethylamino-2-ethyl)9-hydroxy ellipticinium-chloride, HCl.

2-(Diethylamino-2-ethyl)9-hydroxyellipticinium-chloride, HCl (DHE), a new congener of the antitumor agent elliptinium acetate (Celiptium) (NMHE), has recently been selected for phase I clinical trials. NMHE has a methyl group at nitrogen 2 on the ellipticine ring while DHE possesses a basic diethylaminoethyl chain at this position. Compared to NMHE, the presence of the diethylaminoethyl side chain results in the following: a significant increase in the lipophilicity of the drug; no significant modification in either the binding constant values to DNA or the ability to intercalate between DNA base pairs; a marked decrease in the unwinding angle value of supercoiled DNA; and no significant change in the alteration of the catalytic activity of topoisomerase II in vitro. DHE appears to act as a simple reversible intercalating agent as shown by the selective mutagenic effect on Salmonella TA 1977 tester strain and by its inability to induce the SOS functions in a sfiA lac fusion containing Escherichia coli strain. From a pharmacological point of view, the presence of the diethylaminoethyl chain results in a 2-fold increase in the cytotoxicity to L1210 cultured cells, a strong increase in the antitumor efficiency on experimental murine tumors such as L1210 and P388 leukemia, B16 melanoma, M 5076 reticulosarcoma, and colon 38 adenocarcinoma, and finally an objective decrease in the acute and subacute toxicity in mice, rat, and macaque. The absence of significant differences in the interaction of NMHE and DHE with their potential targets in vitro leads to the hypothesis that the superiority of DHE in terms of cytotoxicity and antitumor efficiency may be due to an increase in the diffusion across cellular membrane and a more favorable biodistribution in vivo.

Antisense-mediated repression of DNA topoisomerase II expression leads to an impairment of HIV-1 replicative cycle.

Previously, we have observed a strong restriction of the Moloney murine leukemia virus (MoMLV) replicative cycle in a cell line displaying resistance to topoisomerase II (topo II)-interactive drugs. Resistance towards these antitumoral inhibitors was associated with decreased expression and activity of topo II, suggesting that such a decrease may be responsible for MoMLV restriction. To more specifically assess the role of topo II during the retroviral cycle, we have used the antisense strategy to obtain a selective decrease of cellular topo II expression. The RNA antisense was isolated from a retroviral library expressing random fragments of human topo II (alpha form). This system allowed us to investigate the HIV-1 replicative cycle in two related human CEM cell lines expressing different levels of topo II. Expression of the enzyme is decreased four- to sixfold following formation of a sense-antisense RNA hybrid. Repression of the topo II enzyme results in an impairment of the HIV-1 replicative cycle. Using the polymerase chain reaction, we showed that the number of integration events was decreased in cells repressing the enzyme, although viral DNA synthesis and circularization were equivalent to those in the parent cells.

[Anticoagulation and peripartum management]. / Influence des anticoagulants sur la prise en charge péri-partum.

OBJECTIVE: To compare peripartum management of anticoagulated patients concerning locoregional analgesia, post-partum hemorrhage and thrombotic events according to planified interruption or not of antithrombotic therapy. PATIENTS AND METHODS: We conducted a single tertiary care center retrospective study of all deliveries associated with antithrombotic therapy from January 2005 to September 2011. RESULTS: We identified 120 cases with prophylactic (71%) or curative (29%) anticoagulation. Two thrombotic events occurred. In case of curative therapy, the use of locoregional analgesia was lower (P<0.0001) and post-partum hemorrhage occurred more frequently (P=0.07) compared to prophylactic therapy. According to planified interruption or not of antithrombotic therapy, we observed a more prolonged duration of therapeutic interruption before delivery (55.6h±63.3 vs 26.4 h±11.6, P<0.0001), higher use of locoregional analgesia (83% vs 71%, P=0.02) but no difference concerning cesarean rate (35% vs 39%, P=0.8) or post-partum hemorrhage (13% vs 14%, P=0.9). CONCLUSION: In case of curative anticoagulation, plannified interruption favours the use of perimedullar analgesia after 24hour delay. In case of preventive anticoagulation, plannified interruption appears unnecessary as the 12hour delay is easier to reach.

Inhibitory effects of long term treatment with a luteinizing hormone-releasing hormone agonist on the pituitary-gonadal axis in male and female rats.

Following previous observations of the potent antifertility effects of acute treatment with LHRH or its agonistic analogs in male and female rats, this study describes the effect of long term (up to 12 weeks) treatment with an LHRH agonist, [D-Ala6, des-Gly-NH210]LHRH ethylamide (LHRH-A), on testicular and ovarian gonadotropin receptor levels and function in the rat. Treatment of adult male rats with 100 ng LHRH-A every third day led to a progressive decrease of testis, seminal vesicle, and prostate weight up to 12 weeks of treatment, while the inhibitory effect (70%) on LH receptor levels was already maximal at 1 week. When adult female rats were injected daily with 5 microgram LHRH-A for 12 weeks, ovarian LH, FSH, and PRL receptor levels were reduced 50--90%, while plasma estradiol and progesterone levels were inhibited 60% (compared with diestrus day 1). The effect of chronic administration of a low dose (5 IU) of hCG in the male rat was transient. By contrast, no sign of resistance developed up to 12 weeks of treatment with the LHRH agonist in either male or female animals.

Inhibition of spermatogenesis in the rat by treatment with [D-Ala6, Des-Gly-NH210] LHRH ethylamide.

The effect of treatment with a potent LHRH agonist, [D-Ala6, Des-Gly-NH210]LHRH ethylamide, injected at the low dose of 100 ng, twice a week, was evaluated on spermatogenesis in the rat. Significant degenerative changes of seminiferous tubules could be observed after two weeks of treatment. These changes were progressive and led to a marked inhibition of spermatogenesis after four to eight weeks of treatment. Testis weight was decreased to approximately 50% of control after eight weeks of treatment.