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Study question Does diet-induced weight loss improve semen parameters, and are these possible improvements maintained with sustained weight loss? Summary answer An 8-week low-calorie diet-induced weight loss was associated with improved sperm count, which was maintained after one year in men who maintained weight loss. What is known already Obesity is associated with impaired semen parameters. Weight loss improves metabolic health in obesity, but there is a lack of knowledge on the acute and long-term effects of weight loss on semen parameters. Study design, size, duration This is a substudy of men with obesity enrolled in a randomised, controlled, double-blinded trial (the S-LITE trial). The trial was conducted between August 2016 and November 2019. A total of 56 men was included in the study and assigned to an initial 8-week low-calorie diet (800 kcal/day) followed by randomisation to 52 weeks of either: placebo, exercise training, and placebo (exercise), the GLP-1 analogue liraglutide (liraglutide) or liraglutide in combination with exercise training (combination). Participants/materials, setting, methods Inclusion criteria were men who delivered semen samples, 18 to 65 years of age and a body mass index between 32 to 43 kg/m2, but otherwise healthy. The study was carried out at Hvidovre Hospital and at the University of Copenhagen, and the participants were from the Greater Copenhagen Area. We assessed semen parameters, anthropometrics and collected blood samples before (T0) and after the 8-week low-calorie dietary intervention (T1) and after 52 weeks (T2). Main results and the role of chance The men lost on average 16.5 kg (95% CI: 15.2-17.8) bodyweight during the low-calorie diet, which increased sperm concentration 1.49 fold (95% CI: 1.18-1.88, P Limitations, reasons for caution The S-LITE trial was a randomised controlled trial of weight loss maintenance. Analysis of semen was preregistered to explore the effects of weight loss and weight loss maintenance on semen parameters. Due to the small sample size, definite inferences cannot be made. Wider implications of the findings This study shows that sperm concentration and sperm count were improved after a diet-induced weight loss in men with obesity. Our findings indicate that both liraglutide and exercise as weight maintenance strategies may be used to maintain the improvements in sperm concentration and count. Trial registration number H-16027082

BACKGROUND: Cytomegalovirus (CMV) is a leading infectious cause of neurologic deficits, both in the settings of congenital and perinatal infection, but few animal models exist to study neurodevelopmental outcomes. This study examined the impact of neonatal guinea pig CMV (GPCMV) infection on spatial learning and memory in a Morris water maze (MWM) model. METHODS: Newborn pups were challenged intraperitoneally (ip) with a pathogenic red fluorescent protein (RFP)-tagged GPCMV, or sham-inoculated. On days 15–19 post-infection (pi), pups were tested in the MWM. Viral loads were measured in blood and tissue by quantitative PCR (qPCR), and brain samples collected at necropsy were examined by histology and immunohistochemistry. RESULTS: Viremia (DNAemia) was detected at day 3 pi in 7/8 challenged animals. End-organ dissemination was observed, by qPCR, in lung, liver, and spleen. CD4+ and CD8+ T-cell infiltrates were present in brains of challenged animals, particularly in periventricular and hippocampal regions. Reactive gliosis and microglial nodules were observed. Statistically significant spatial learning and memory deficits were observed by MWM, particularly for total maze distance travelled (p

Otolaryngology is an ever-changing practice. Staying abreast with societal recommendations while providing technologically current treatment paradigms remains a cornerstone of up-to-date patient care. This chapter reflects on the role of the otolaryngologist in the outpatient setting and details prior knowledge as it pertains to litigious inquiry. The hope of the authors is to provide objective data and clinical pearls useful while avoiding the courtroom. No knowledge outweighs the dynamic role of a practitioner patient relationship, but this chapter helps to fill gaps of knowledge regarding liability and litigation.

Primary Zika virus (ZIKV) infections that occur during pregnancy can cause spontaneous abortion and profoundly disrupt fetal development. While the full range of developmental abnormalities associated with congenital Zika syndrome is not yet known, severe cases of the syndrome can present with microcephaly, extensive neurologic and ocular damage, and pronounced joint malformations. Animal models that accurately recapitulate congenital Zika syndrome are urgently needed for vaccine development and for the study of ZIKV pathogenesis. As guinea pigs have successfully been used to model transplacental infections by cytomegalovirus, syphilis, and Listeria monocytogenes, we sought to test whether ZIKV could productively infect guinea pigs and whether viral transmission with attendant fetal pathology would occur after a mid-gestation viral challenge. We found that guinea pig cells supported ZIKV replication in vitro. Experimental infection of non-pregnant animals did not result in overt disease but low-level, detectable viremia was observed. When pregnant guinea pigs were challenged with ZIKV at between 18 and 21 days gestational age, ZIKV was not detected in maternal or pup blood, plasma, or tissues and no significant differences in maternal weight gain or pup size were observed following challenge. Nonetheless, a robust antibody response against ZIKV was detected in both the pups and dams. These results suggest that, while guinea pigs can model aspects of the immune response to ZIKV infection during pregnancy, naturally circulating ZIKV strains are not pathogenic during the pregnancy of immunocompetent guinea pigs and do not interfere with normal pup development.

OBJECTIVES We investigated the relationships among positivity, perceived personal and environmental resources, and emotional dysfunction in adolescent girls. We hypothesized that perceived resources would mediate the relationship between positivity and emotional dysfunction. METHODS Participants (N = 510) attending an all-girls public school completed a survey assessing emotional dysfunction (depressive symptoms and perceived stress), positivity (positive/negative emotions), and personal/ environmental resources (resilience, hope, percent adaptive coping, community connectedness, social support, and school connectedness). Perceived resources were combined into one latent variable, and structural equation modeling tested the mediating effect of perceived resources on the relationship between positivity and emotional dysfunction. RESULTS The model accounted for 63% of the variance in emotional dysfunction. Positivity exerted a significant direct effect on emotional dysfunction (β = -.14, p < .01), but its influence was primarily mediated through perceived resources (indirect effect: β = -.43, p < .001). CONCLUSIONS The impact of positivity on emotional dysfunction is primarily but not entirely mediated by perceived personal and environmental resources. Schools should consider strategies to enhance experiences of positive emotions and/or decrease experiences of negative emotions, in conjunction with encouraging student awareness and development of personal and environmental resources.

Background: The benefits of a broadened mind set across moments of positivity accumulate over time and build enduring personal resources. Positivity can transform one’s life for the better, enhancing health and building greater resilience to adversity. Evidence is strong that positivity is a key active ingredient in flourishing mental health, however, less is known about the upper limit of positivity for optimal functioning. Aim: This study examined if exceedingly high positivity ratios – experienced positive to negative emotions – were associated with increased emotional dysfunction (stress, depressive symptoms) and downturned perceived personal (resilience, hope) and environmental (social support, school connectedness) resources. Methods: Participants (N=510) attending an all-girls public school completed a survey assessing positive/negative emotions (the positivity ratio), emotional dysfunction, and perceived personal and environmental resources. Linear and quadratic regression equations for the relationship between the positivity ratio and emotional dysfunction and perceived resources were modeled and compared. Results: The relationships between the positivity ratio and both emotional dysfunction and perceived resources were best fit by quadratic equations, indicative of enhanced functioning up to a point, beyond which functioning decreased at the highest levels of positivity. Conclusion: More frequent experiences of positive emotions and/or less frequent experiences of negative emotions are adaptive, within bounds, in promoting emotional functioning and helping adolescents perceive greater availability of personal and environmental resources.

Study Design Case report. Clinical Question The clinical aim is to report on a previously unknown association between guidewire-assisted pedicle screw insertion and neuropraxia of the recurrent laryngeal nerve (RLN), and how this may overlap with the signs of Tapia syndrome; we also report our approach to the clinical management of this patient. Methods A 17-year-old male patient with idiopathic scoliosis experienced Tapia syndrome after posterior instrumentation and arthrodesis at the level of T1–L1. After extubation, the patient had a hoarse voice and difficulty in swallowing. Imaging showed a breach in the cortex of the anterior body of T1 corresponding to the RLN on the right. Results Otolaryngological examination noted right vocal fold immobility, decreased sensation of the endolarynx, and pooling of secretions on flexible laryngoscopy that indicated right-sided cranial nerve X injury and left-sided tongue deviation. Aspiration during a modified barium swallow prompted insertion of a percutaneous endoscopic gastrostomy tube before the patient was sent home. On postoperative day 20, a barium swallow demonstrated reduced aspiration, and the patient reported complete resolution of symptoms. The feeding tube was removed, and the patient resumed a normal diet 1 month later. Tapia syndrome, or persistent unilateral laryngeal and hypoglossal paralysis, is an uncommon neuropraxia, which has previously not been observed in association with a breached vertebral body at T1 along the course of the RLN. Conclusion Tapia syndrome should be a differential diagnostic consideration whenever these symptoms persist postoperatively and spine surgeons should be aware of this as a potential complication of guidewires in spinal instrumentation.

The supply of fosfomycin had to be carefully controlled over metropolitan France during 10 weeks because of a unique crisis in production. Three hundred and forty prescriptions were collected and re-examined by an expert committee. The main indications were osteoarthritis (27%), lung infections (21%), severe sepsis (12.5%), and urinary tract infections (11%). The main bacteria involved, often multidrug resistant, were Pseudomonas aeruginosa (40%) and methicillin-resistant Staphylococcus. A careful analysis of the antibiogram proved fosfomycin to be irreplaceable in 36% of the cases. This study confirms and specifies the interest of fosfomycin. To our knowledge, this study was a unique opportunity to collect such specific data from the whole of France over a two-month shortage period.

The most profound deficits observed in Alzheimer's disease (AD) are in domains of episodic and working memory systems. Transgenic (Tg) mice expressing mutated human amyloid precursor protein (APP) genes offer a model to study the effect of AD pathology on cognition. We reported previously that APP TgCRND8 mice showed deficits in a reference and working memory evaluated in a Morris water-maze test. In this study, we evaluated the working memory of TgCRND8 mice comparing two training paradigms in a six-arm radial water maze. In the first paradigm, the exploration of the maze was constrained, forcing the mice to use a spatial mapping strategy. In the second paradigm, mice were unconstrained in their exploration of the maze. TgCRND8 mice proved to be significantly impaired in spatial working memory in both paradigms as compared with their non-transgenic littermates. The analysis of data revealed that forcing mice to use a spatial strategy during training caused only a moderate improvement in the performance of all mice. However, unconstrained exploration of the maze not only resulted in a fast learning in control mice, but also facilitated the development of a chaining strategy in spatially impaired TgCRND8 mice. In conclusion, TgCRND8 mice showed impairment in spatial working memory but retained a plasticity to choose alternative search strategies.

T. Dobzhansky (1973) has been credited with saying: 'nothing in biology makes sense, except in the light of evolution'. The evolutionary conservation of gene function, as well as remarkable conservation of elemental behavioral mechanisms, guarantees that much of what we learn in one organism will inform our understanding of behavior in all animals, including humans. This insight has permitted behavior-geneticists to choose organisms based on experimental tractability for a given scientific question. IBANGS as a society has clearly embraced this Dobzhanskian worldview. As a result, the intellectual synergy of cross-species behavior-genetic analysis was palpable at the IBANGS meeting in Tours, France.

A novel technique for controlling oscillating combustion is proposed and demonstrated. For oscillations that exist over a limited range of equivalence ratios, we suggest that periodic modulation around the unstable condition can effectively avoid the oscillating condition, but otherwise produces the desired timeaverage equivalence ratio. Tests of this concept were carried out in an atmospheric-pressure, swirl-stabilized combustor with a nominal heat input of 30 kW. The fuel was natural gas. We show that it was possible to control a 300-Hz oscillation by modulating the fuel flow at frequencies less than 20 Hz, reducing the observed rms pressure from 2.7 to 0.8 kPa. Limitations on when this technique may produce successful control are also discussed.

The use of premix combustion in stationary gas turbines can produce very low levels of Nox emissions. This benefit is widely recognized, but turbine developers routinely encounter problems with combustion oscillations during the testing of new premix combustors. Because of the associated pressure fluctuations, combustion oscillations must be eliminated in a final combustor design. Eliminating these oscillations is often time-consuming and costly because there is no single approach to solve an oscillation problem. Previous investigations of combustion stability have focused on rocket applications, industrial furnaces, and some aeroengine gas turbines. Comparatively little published data is available for premixed combustion at conditions typical of an industrial gas turbine. In this paper, we report experimental observations of oscillations produced by a fuel nozzle typical of industrial gas turbines. Tests are conducted in a specially designed combustor capable of providing the acoustic feedback needed to study oscillations. Tests results are presented for pressure up to 10 atmospheres, with inlet air temperatures up to 588 K (600 F) burning natural gas fuel. Based on theoretical considerations, it is expected that oscillations can be characterized by a nozzle reference velocity, with operating pressure playing a smaller role. This expectation is compared to observed data that shows both the benefits and limitations of characterizing the combustor oscillating behavior in terms of a reference velocity rather than other engine operating parameters. This approach to characterizing oscillations is then used to evaluate how geometric changes to the fuel nozzle will affect the boundary between stable and oscillating combustion.

We have assessed the effects of zopiclone (7.5 mg), a new cyclopyrrolone hypnotic drug, on ventilation, sleep parameters, and daytime vigilance in snorers with upper airway resistance syndrome (UARS). Using a randomized double-blind design, eight male patients with UARS took either oral zopiclone or a placebo each evening for seven consecutive days and then crossed over to the other drug after a 7 day placebo period. Polysomnography followed by a multiple sleep latency test (MSLT) was performed during the last night of each treatment period. Zopiclone produced significant improvements in the sleep efficiency index (total sleep time/time in bed) (placebo 84+/-15% versus zopiclone 91+/-7%) and average MSLT (placebo 10.3+/-3.7 min versus zopiclone 14.9+/-2.8 min), as well as nonsignificant improvements in sleep onset latency and total sleep time. It had no effect on sleep architecture or on the arousal index (placebo 17+/-8 arousals x h(-1) versus zopiclone 17+/-4 arousals x h[-1]). Furthermore, none of the respiratory parameters were significantly affected by zopiclone. In conclusion, zopiclone has no adverse effects on sleep architecture, respiratory parameters during sleep, and daytime sleepiness in patients with UARS.

Although pulse combustion has been successfully utilized in various commercial applications, one potential application yet to reach the market is the pressure gain gas turbine (PGGT). A PGGT would incorporate a pulse combustor rather than the typical steady-flow combustor to increase system efficiency and decrease pollutant emissions. The distinctive advantage of pulse combustion is its ability to achieve a stagnation pressure gain from inlet to exit. A primary concern with pressure gain combustion development, however, is the lack of understanding as to how a combustor should be designed to achieve a pressure gain. While significant progress has been made in understanding the fundamental controlling physics of pulse combustor operation, little research has been aimed at understanding and predicting whether a given system will produce pressure gain. The following paper proposes a simple framework which helps to explain how a pulse combustor achieves a stagnation pressure gain from inlet to exit. The premise behind the framework is that pressure gain can be achieved by closely approximating a constant volume combustion process, and a constant volume combustion process is closely approximated by matching the resonant and operating frequencies of the system. The framework is primarily based upon results from a one-dimensional method-of-characteristics model.

SummaryThe effect of zopiclone (7.5 mg) on attention, vigilance and memory components was evaluated during a nocturnal period in comparison to a placebo, to zolpidem (10 mg) and to flunitrazepam (1 mg) in a double blind, randomized study, after administration of a single dose in 16 young healthy volunteers. It appears that there is a clear effect on attention and vigilance; this effect is apparent during the kinetic phase of the absorption of the medication. The effect on memory is transient and is absent four hours after the ingestion of the drug. The objective results are not strictly consistent with the chronology of the subjective parameters (Leeds scale — Visual Analogue Scale). The three hypnotics under comparison do not fundamentally differ except in their kinetic/pharmacodynamic effect relationship. One important fact, taking the parameters as a whole, is that there is no objective “residual” effect.

SummaryFrom 20,000 households regularly surveyed by a national survey institute (Sofres), two groups were selected and questioned (using a 23-item questionnaire) about sleep vigilance and quality of life. The first group was composed of insomniacs using zopiclone for the last 12 months and no other CNS treatments (167 subjects). The second group was composed of 381 “good sleepers” selected as having no or occasionally one sleep disturbance in the last 12 months. No difference was found between the two groups in average total sleep time. Sleep disturbances were statistically equal in the two groups except for difficulties in initiating sleep which is more present for zopiclone users (13% vs 3%). Vigilance was mostly comparable in both groups.Five aspects of quality of life explored by the questionnaires (the professional, relational and sentimental, domestic, leisure and safety aspects) appeared to be comparable in the two groups.

SummaryTwo distinct double-blind randomized multicentre studies were undertaken at the same time using the same design. Patients treated for insomnia with zopiclone 7.5 mg or zolpidem 10 mg for at least three months were allocated to two groups: gradual withdrawal or control. In each study the two groups were compared but there was no comparison between zopiclone and zolpidem. The main criteria was the number of patients in each group with “withdrawal syndrome” defined as: the occurrence of an adverse event, or premature discontinuation of treatment or a total score increase of at least 3 points on the Tyrer questionnaire. In both studies the incidence of “withdrawal syndrome” as defined above was significantly higher in the “withdrawal” groups than in the “control” groups 38% vs 20% for zopiclone p = 0.008 and 38% vs 24% for zolpidem P = 0.049. In most cases, the notified symptoms were sleep complaints.

Neuronal cell death underlies the majority of age-related human neurodegenerative disorders that culminate with salient and severe cognitive decline affecting patients' quality of life, identity and eventually leading to death. The identification of disease-causing genes in familial forms of neurodegenerative diseases enabled the development of genetic models closely replicating pathologies found in human central nervous system. These models dramatically precipitated our understanding of molecular events leading to neuronal death in many neurodegenerative disorders. Today's large range of cellular and animal models generate rapidly accumulating biochemical and neuropathological data on changes induced by mutated or dysfunctional proteins implicated in neuronal loss. Most of these models are complementary, although all have intrinsic limitations as well as specific advantages. Development of conditional transgenic mouse models in which a deleterious effect of a transgene can be regulated in a controlled way created new possibilities of addressing the basic mechanisms of neurodegeneration and provided a new angle for the development and testing of new therapeutic approaches.

The supply of fosfomycin had to be carefully controlled over metropolitan France during 10 weeks because of a unique crisis in production. Three hundred and forty prescriptions were collected and re-examined by an expert committee. The main indications were osteoarthritis (27%), lung infections (21%), severe sepsis (12.5%), and urinary tract infections (11%). The main bacteria involved, often multidrug resistant, were Pseudomonas aeruginosa (40%) and methicillin-resistant Staphylococcus. A careful analysis of the antibiogram proved fosfomycin to be irreplaceable in 36% of the cases. This study confirms and specifies the interest of fosfomycin. To our knowledge, this study was a unique opportunity to collect such specific data from the whole of France over a two-month shortage period.

OBJECTIVES/HYPOTHESIS: Nuclear factor (NF)-kappaB is an early response gene that has been associated with head and neck squamous cell cancer (HNSCC) progression. NF-kappaB activation is induced by some chemotherapy agents, including paclitaxel. The activation of this gene can be correlated with apoptosis resistance. Inositol hexaphosphate (IP6) is a naturally occurring polyphosphorylated carbohydrate. NF-kappaB levels were evaluated in oral cavity HNSCC lines after treatment with paclitaxel and IP6, alone and in combination. Resulting levels of cell death and apoptosis were assessed, and conclusions are drawn regarding a possible synergistic relationship between paclitaxel and IP6. METHODS: NF-kappaB activation in cancer cells treated with paclitaxel and IP6, alone and in combination, was measured by transient transfection, and results were interpreted by luminometry. Cell proliferation of treated cells was measured by MTT assay. Cell viability and apoptosis of cancer cells treated with paclitaxel and IP6 combinations were quantitated by trypan blue staining and Caspase-Glo 3/7 assay, respectively. RESULTS: IP6 was observed to significantly downregulate NF-kappaB activation in both NA and CA-9-22 oral cavity HNSCC cell lines. Paclitaxel treatments caused increased NF-kappaB activation in the same cell lines. IP6 was observed to mitigate paclitaxel-induced NF-kappaB activation in the CA-9-22 cell line. IP6, when combined with paclitaxel, reduces CA-9-22 cell proliferation, increases cell death, and increases apoptosis, when compared with treatment with paclitaxel alone. CONCLUSIONS: IP6 reduces paclitaxel induced NF-kappaB activation and increases paclitaxel-mediated cell killing and apoptosis. As a well-tolerated and safe supplement, IP6 deserves further study in the treatment of oral cavity squamous cell carcinoma.

Recent regulations on NOx emissions are promoting the use of lean premix (LPM) combustion for industrial gas turbines. LPM combustors avoid locally stoichiometric combustion by premixing fuel and air upstream of the reaction region, thereby eliminating the high temperatures that produce thermal NOx. Unfortunately, this style of combustor is prone to combustion oscillation. Significant pressure fluctuations can occur when variations in heat release periodically couple to acoustic modes in the combustion chamber. These oscillations must be controlled because resulting vibration can shorten the life of engine hardware. Laboratory and engine field testing have shown that instability regimes can vary with environmental conditions. These observations prompted this study of the effects of ambient conditions and fuel composition on combustion stability. Tests are conducted on a subscale combustor burning natural gas, propane, and some hydrogen/hydrocarbon mixtures. A premix, swirl-stabilized fuel nozzle typical of industrial gas turbines is used. Experimental and numerical results describe how stability regions may shift as inlet air temperature, humidity, and fuel composition are altered. Results appear to indicate that shifting instability regimes are primarily caused by changes in reaction rate.

The use of premix combustion in stationary gas turbines can produce very low levels of NOx emissions. This benefit is widely recognized, but turbine developers routinely encounter problems with combustion oscillations during the testing of new pre mix combustors. Because of the associated pressure fluctuations, combustion oscillations must be eliminated in a final combustor design. Eliminating these oscillations is often time-consuming and costly because there is no single approach to solve an oscillation problem. Previous investigations of combustion stability have focused on rocket applications, industrial furnaces, and some aeroengine gas turbines. Comparatively little published data is available for premised combustion at conditions typical of an industrial gas turbine. In this paper, we report experimental observations of oscillations produced by a fuel nozzle typical of industrial gas turbines. Tests are conducted in a specially designed combustor, capable of providing the acoustic feedback needed to study oscillations. Tests results are presented for pressures up to 10 atmospheres, and with inlet air temperatures to 588 K (600 F) burning natural gas fuel. Based on theoretical considerations, it is expected that oscillations can be characterized by a nozzle reference velocity, with operating pressure playing a smaller role. This expectation is compared to observed data, showing both the benefits and limitations of characterizing the combustor oscillating behavior in terms of a reference velocity rather than other engine operating parameters. This approach to characterizing oscillations is then used to evaluate how geometric changes to the fuel nozzle will affect the boundary between stable and oscillating combustion.

The aim of this double-blind, 2 parallel group, randomized, multicenter study was to compare the efficacy and the safety of pristinamycin (P), 1 g bid, versus amoxicillin-clavulanic acid (AAC), 500 mg q.i.d., for 10-14 days in the treatment of non severe community-acquired pneumonia in hospitalized adults. From December 1992 to July 1994, 180 patients were included: 92 in the group P and 88 in the group AAC. The both groups were similar on demographic, clinical and bacteriological criteria. 96 pathogens of which more than half were pneumococci, were isolated in 79/180 (44%) patients. The primary assessment was the global success rate defined as long-term (D40 +/- 7), clinical, radiological and bacteriological efficacy in the "per protocol" population (75 patients in the group P and 83 in the group AAC). The global success was obtained in 63/75 (84%) patients in the group P and 70/83 (84.3%) patients in the group AAC. At the end of treatment (D14 +/- 3), theses rates were respectively 85.4% and 84.3%. The both treatments were equivalents. Adverse events (mainly gastro-intestinal disorders) were reported by 55/92 (59.8%) patients in the group P and 49/87 (56.2%) patients in the group AAC.

beta-S100 is a calcium-binding protein in the CNS which is involved in the development of the nervous system. In addition, it has been postulated to play a role in long-term potentiation (LTP) in the hippocampus. To test its role in behavior related to hippocampal function, the gene was overexpressed (80 copies) in CD-1 transgenic mice, and the exploration of a novel environment was examined in two experiments. In both experiments subjects' exploratory behavior was observed in an open-field arena containing four objects. No differences in emotional behavior were found between transgenic mice and their controls as measured by the subjects' motility, defecation, and urination. The results of Experiment 1 revealed that transgenic mice explored objects significantly less than the controls, and they did not respond overtly to the spatial change after object displacement. The control CD-1 subjects, on the other hand, showed increased selective reexploration of the displaced object. The results of Experiment 2 replicated the findings of Experiment 1 and revealed more subtle differences in object exploration between the groups. Transgenic mice climbed objects less often and they had longer latencies of object approach than normal CD-1 mice. The study suggests the possible involvement of beta-S100 protein in general exploratory behavior, which includes learning of spatial characteristics of the environment. Specifically, the overexpression of the beta-S100 gene seems to affect the subjects' reactivity to the arousal-inducing properties of novel stimuli.

The effect of an enriched rearing environment on exploration of 4- and 8-arm radial mazes was investigated in CD-1 mice. Subjects in enriched (EC) and standard (SC) environmental conditions were socially reared with the exception that various objects and a running wheel were added into the EC cages. Non-deprived subjects were allowed to explore individually an appropriate maze for 10-min periods on two successive days (Days 1 and 2 of the experiment). After the second exploration session subjects were deprived of water for 12 h before the test which was administered on Day 3 of the experiment. Subjects from both groups performed similarly in the 4-arm radial maze, finding the arm containing water with comparable latency and erroneous entries to other, not containing water, arms. However, the more complex, 8-arm radial maze significantly differentiated the behaviour of both groups. EC subjects showed faster habituation to the maze than SC subjects, decreasing significantly their locomotor behaviour during second exploratory session. During the test, EC subjects found and drank water within significantly shorter time, making fewer errors. It is suggested that subtle behavioural changes caused by different rearing environments might be more readily detectable in the early phases of solving more complex behavioural tasks by mildly motivated animals.

Objectif Examiner les prescriptions de fosfomycine (FOS), ses indications et son efficacite en periode de contingentement. Durant une periode de 10 semaines la production de FOS a ete interrompue, et sa delivrance contingentee. Les prescriptions ont ete revues par un comite d’experts. Ont ete etudie, 114 prescriptions concernant 46 femmes et 68 hommes, 86 % d’adultes et 14 % d’enfants. Les principales bacteries identifiees etaient Pseudomonas aeruginosa (Pa) (36 %), Staphylococcus aureus meticilline-resistant (SARM) (30 %), Escherichia coli (E. coli), et les bacteries du groupe KES (Klebsiella, Enterobacter, Serratia) ; 67,5 % des bacteries etaient multi-resistantes (BMR). D’apres l’analyse des antibiogrammes la FOS etait le seul antibiotique efficace dans 35 % des cas. Indications Total Germes responsables Antibiotiques associes Duree moyenne de traitement en jours Evolution Osteo arthritis 31 SARM : 9 C3G : 9 28 Favorable : 25 SARM : 3 GP : 8 Defavorable : 5 Pa : 5 Imipeneme : 4 NR : 1 E. coli : 5 KES : 5 FQ : 2 Infections pulmonaires 29 Pa : 20 Imipeneme : 5 11,5 Favorable: 21 SARM : 3 Colimycine : 5 Defavorable : 7 SCNMR : 1 C3G : 3 NR : 1 KES : 1 Autres : 5 Infections urinaires 14 Pa : 10 C3G : 6 9,9 Favorable: 14 E. coli : 2 Imipeneme : 2 SARM : 2 Colimycine : 1 FQ : 1 Sepsis 13 SCNMR : 5 GP:6 12,8 Favorable : 8 SARM : 2 C3G:2 Defavorable : 3 E. coli : 2 NR : 2 KES : 2 Autres:1 Infections neurologiques 8 SAMS2 : 2 C3G : 2 9,6 Favorable : 6 KES : 2 GP : 1 Defavorable : 1 SARM : 1 Meropeneme : 1 NR : 1 SCNMR : 1 NR : 4 E. coli :1 NR : 1 SCNMR : staphylocoque a coagulase negative meticilline resistants ; SAMS : Staphylococcus aureus meticilline sensibles ; C3G : cephalosporine 3e generation ; GP : Glycopeptides ; FQ : fluoroquinolones ; NR : non renseigne. 18 % des patients presentait une bacteriemie et 17 % un choc septique ; 46,5 % etait immunodeprime et 68 % hospitalise en unite de soins intensifs. L’evolution etait favorable dans 89,5 % des cas. Ces resultats suggerent l’efficacite de la FOS dans le traitement des infections severes y compris a BMR

ObjectiveTo evaluate the complication rate in relation to the timing of surgical repair of midface fractures.Study Design and SubjectsRetrospective chart review at a level 1 trauma center.ResultsThirty-four patients were evaluated. Overall complication rate was 23.5% with no significant difference between the early repair (21.1%) and late repair (26.7%) groups. The scope of facial fracture repair was similar between the two groups as measured by the number of screws used and through an injury quantifying system. The only variable that tended toward significance was intraoperative blood loss, which was greater in the early repair group (P = 0.06).ConclusionsThere is no clear consensus with respect to timing of midface trauma repair. Early repair may result in greater blood loss. Further study is needed to help establish a more precise recommendation for the timing of midface trauma repair.

We have used a single intensive chemotherapy regimen in the treatment of young patients with diffuse, aggressive, malignant lymphomas. There were two major histologic types of lymphoma in our series: lymphoblastic lymphomas, which presented most often with mediastinal tumor (64%), and undifferentiated lymphomas (mostly Burkitt’s lymphomas), which occurred predominantly in the abdomen (86%). Our objective was to examine the determinants of prognosis in a uniformly treated patient group that included 31 children (2–16 yr) and 34 young adults 17–35 yr). Patients with extensive bone marrow involvement (greater than 50% replacement by tumor cells) were included in the study. Treatment consisted essentially of a 4-drug combination (cytoxan, adriamycin, vincristine, and prednisone) alternating with a 42-hr methotrexate infusion, followed by leukovorin rescue, and included intrathecal prophylactic therapy against central nervous system (CNS) disease. Patients with localized or resected undifferentiated lymphoma received 6 therapy cycles; all other patients received 15 cycles. Radiation therapy was used only in exceptional circumstances. Fifty-eight of 65 patients (89%) achieved complete remission: 97% of children and 82% of adults. The estimated 3-yr survival was 60% (SE 6.4%) with a median follow-up of 3 yr. Analysis of factors associated with remission duration and survival indicated that bone marrow involvement at referral and extensive disease were poor prognostic variables. Patients with lymphoblastic lymphomas and patients with completely resected undifferentiated lymphomas had the best prognosis (81% +/- 12% and 94% +/- 6% estimated 3-yr survival, respectively). Patients with extensive intraabdominal undifferentiated lymphoma (stage D) had the worst prognosis (33% +/- 11% estimated 3 yr survival), but even in this subgroup, bone marrow involvement was an adverse factor (estimated survival in stage D patients with and without bone marrow involvement was 14% +/- 13% and 43% +/- 15%, respectively). Elevated uric acid and/or lactic dehydrogenase (LDH) were also of prognostic significance, but predominantly reflected state, i.e., extent of disease. Age did not significantly influence prognosis. In the undifferentiated lymphoma subgroup, histology (i.e., Burkitt's lymphoma versus non-Burkitt’s lymphoma) was not of prognostic significance. Total white count was below 1,000/cu mm in 39% of cycles, and fever associated with granulocytopenia occurred in 17% of cycles. Stomatitis of moderate to severe extent occurred in 50% of cycles.(ABSTRACT TRUNCATED AT 400 WORDS)

We have used a single intensive chemotherapy regimen in the treatment of young patients with diffuse, aggressive, malignant lymphomas. There were two major histologic types of lymphoma in our series: lymphoblastic lymphomas, which presented most often with mediastinal tumor (64%), and undifferentiated lymphomas (mostly Burkitt’s lymphomas), which occurred predominantly in the abdomen (86%). Our objective was to examine the determinants of prognosis in a uniformly treated patient group that included 31 children (2–16 yr) and 34 young adults 17–35 yr). Patients with extensive bone marrow involvement (greater than 50% replacement by tumor cells) were included in the study. Treatment consisted essentially of a 4-drug combination (cytoxan, adriamycin, vincristine, and prednisone) alternating with a 42-hr methotrexate infusion, followed by leukovorin rescue, and included intrathecal prophylactic therapy against central nervous system (CNS) disease. Patients with localized or resected undifferentiated lymphoma received 6 therapy cycles; all other patients received 15 cycles. Radiation therapy was used only in exceptional circumstances. Fifty-eight of 65 patients (89%) achieved complete remission: 97% of children and 82% of adults. The estimated 3-yr survival was 60% (SE 6.4%) with a median follow-up of 3 yr. Analysis of factors associated with remission duration and survival indicated that bone marrow involvement at referral and extensive disease were poor prognostic variables. Patients with lymphoblastic lymphomas and patients with completely resected undifferentiated lymphomas had the best prognosis (81% +/- 12% and 94% +/- 6% estimated 3-yr survival, respectively). Patients with extensive intraabdominal undifferentiated lymphoma (stage D) had the worst prognosis (33% +/- 11% estimated 3 yr survival), but even in this subgroup, bone marrow involvement was an adverse factor (estimated survival in stage D patients with and without bone marrow involvement was 14% +/- 13% and 43% +/- 15%, respectively). Elevated uric acid and/or lactic dehydrogenase (LDH) were also of prognostic significance, but predominantly reflected state, i.e., extent of disease. Age did not significantly influence prognosis. In the undifferentiated lymphoma subgroup, histology (i.e., Burkitt's lymphoma versus non-Burkitt’s lymphoma) was not of prognostic significance. Total white count was below 1,000/cu mm in 39% of cycles, and fever associated with granulocytopenia occurred in 17% of cycles. Stomatitis of moderate to severe extent occurred in 50% of cycles.(ABSTRACT TRUNCATED AT 400 WORDS)

As part of an investigation of the cellular origins of undifferentiated lymphomas of the Burkitt's and non-Burkitt's types, we have examined immunoglobulin secretion by cell lines and biopsy samples from these tumors and have compared it with other lymphoblastoid cell lines. The majority of American lymphoma cell lines and a smaller fraction of African lymphoma cell lines secreted monoclonal IgM. No other Ig classes were secreted. Ig secretion by the tumor samples was also found to be exclusively IgM. The secreted IgM was polymeric and associated with J chain. Secretion of free light chain by most of the tumor cell lines was observed. Quantitation by immunoassay demonstrated that the American lymphoma cell lines secreted significantly more IgM than the African lymphoma cell lines. We have proposed that the lymphoma cells represent an early stage of B cell differentiation, during which antigen-independent secretion occurs.

Sixty-four patients with American Burkitt's lymphoma (AMBL) treated at the National Cancer Institute were reviewed to determine the frequency and characteristics of central nervous system (CNS) involvement. Patients with minimal or completely resected tumor never had CNS disease. Of the 45 patients with more extensive disease, 15 had CNS disease: nine presented with CNS disease, six of whom subsequently had recurrent CNS disease, and six developed CNS disease only at relapse. There was a significant association between CNS and bone-marrow disease at presentation. Therapy of CNS disease consisted of short courses of intrathecal chemotherapy with cytosine arabinoside and methotrexate. Cranial irradiation was given only to patients with CNS relapse. There are six long-term survivors (LTS) who have been disease free for four to six years post chemotherapy. Of these six LTS, three presented with CNS disease, two experienced isolated CNS relapse, and one had CNS disease both at presentation and at relapse. Three of the six LTS never received cranial irradiation. It is concluded that CNS involvement in AMBL can be effectively treated, and that long-term remission, which is probably cure, can be achieved.

Fourteen patients (less than or equal to 35 years of age) with intra-abdominal undifferentiated lymphomas, without evidence of disease elsewhere, were treated by surgical resection and six cycles of combination chemotherapy which included cyclophosphamide, vincristine, doxorubicin, prednisone, and 42-hour methotrexate infusion with leucovorin rescue. One patient with very extensive retroperitoneal disease prior to surgery had rapid tumor regrowth and subsequently died. One patient has relapsed twice, but is currently alive and has been disease-free for 2 years. All other patients have remained in complete remission for 25-63 months from presentation. The major toxic effects encountered in this protocol were mucositis (which necessitated a reduction in methotrexate duration in two patients) and fever and neutropenia (which complicated chemotherapy in 15 of the total of 79 cycles delivered). There were three documented infections; all were diagnosed before chemotherapy was started, and all resolved with appropriate antibiotic treatment. The 92% actuarial survival rate in this protocol is comparable to results with more prolonged chemotherapy or a combination of prolonged chemotherapy and irradiation. Since prolonged maintenance therapy and irradiation were not utilized in our protocol, they appear to be unnecessary for patients with intra-abdominal undifferentiated lymphoma whose disease can be at least 90% resected.

Two hundred seventy-five patients with breast cancer and no axillary metastases had mastectomies and axillary node dissection performed during the period between 1970 and 1979 at The Fox Chase Cancer Center. They had a mean age of 60 years (range, 21-91) and 38 (14%) patients have had recurrence to date. Poor histologic differentiation and skin involvement were related to a high risk of recurrence. Those patients with skin infiltration by tumor or a poorly differentiated tumor had a 53 +/- 9% expected five-year tumor-free survival, whereas patients without these had a 90 +/- 2% expected five-year tumor-free survival. Tumor involvement of the lymphatic vessels within the breast and estrogen receptor protein positivity or negativity were not helpful for identifying a subpopulation at increased risk of recurrence. Large tumor size was not a poor prognostic indicator for a patient subpopulation. These factors should be considered as indicators for inclusion in clinical trials and adjuvant therapy and used as stratification points for the analysis of the data developed in these trials.

The term Krukenberg tumor refers to metastatic disease to the ovary and more specifically those metastases containing mucin-secreting signet cells. When this definition is used most of these tumors arise in the gastrointestinal tract although the term Krukenberg tumor has also been used more loosely to describe metastatic disease to the ovary from other sites such as breast and genital tract. On ultrasound examination, the Krukenberg tumor has been described as a complex type of mass showing both solid and cystic characteristics. When a mass with these echographic characteristics is found on pelvic sonography it is important to consider this entity in the differential diagnosis.

We have used a single intensive chemotherapy regimen in the treatment of young patients with diffuse, aggressive, malignant lymphomas. There were two major histologic types of lymphoma in our series: lymphoblastic lymphomas, which presented most often with mediastinal tumor (64%), and undifferentiated lymphomas (mostly Burkitt's lymphomas), which occurred predominantly in the abdomen (86%). Our objective was to examine the determinants of prognosis in a uniformly treated patient group that included 31 children (2-16 yr) and 34 young adults 17-35 yr). Patients with extensive bone marrow involvement (greater than 50% replacement by tumor cells) were included in the study. Treatment consisted essentially of a 4-drug combination (cytoxan, adriamycin, vincristine, and prednisone) alternating with a 42-hr methotrexate infusion, followed by leukovorin rescue, and included intrathecal prophylactic therapy against central nervous system (CNS) disease. Patients with localized or resected undifferentiated lymphoma received 6 therapy cycles; all other patients received 15 cycles. Radiation therapy was used only in exceptional circumstances. Fifty-eight of 65 patients (89%) achieved complete remission: 97% of children and 82% of adults. The estimated 3-yr survival was 60% (SE 6.4%) with a median follow-up of 3 yr. Analysis of factors associated with remission duration and survival indicated that bone marrow involvement at referral and extensive disease were poor prognostic variables. Patients with lymphoblastic lymphomas and patients with completely resected undifferentiated lymphomas had the best prognosis (81% +/- 12% and 94% +/- 6% estimated 3-yr survival, respectively). Patients with extensive intraabdominal undifferentiated lymphoma (stage D) had the worst prognosis (33% +/- 11% estimated 3 yr survival), but even in this subgroup, bone marrow involvement was an adverse factor (estimated survival in stage D patients with and without bone marrow involvement was 14% +/- 13% and 43% +/- 15%, respectively). Elevated uric acid and/or lactic dehydrogenase (LDH) were also of prognostic significance, but predominantly reflected state, i.e., extent of disease. Age did not significantly influence prognosis. In the undifferentiated lymphoma subgroup, histology (i.e., Burkitt's lymphoma versus non-Burkitt's lymphoma) was not of prognostic significance. Total white count was below 1,000/cu mm in 39% of cycles, and fever associated with granulocytopenia occurred in 17% of cycles. Stomatitis of moderate to severe extent occurred in 50% of cycles.(ABSTRACT TRUNCATED AT 400 WORDS)