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Background: Life-space mobility (LSM) captures a broad spectrum of mobility in physical and social environments; however, it has not been extensively studied in Parkinson's disease. Using a multiple-methods approach, individual, social and environmental factors that impact LSM were explored in PD., Methods: Two hundred twenty-seven participants with PD (n = 113) and a comparative group without PD (n = 114) were recruited from the community. Within a cross-sectional survey, LSM (University of Alabama Birmingham Life-Space Assessment, LSA) was compared in the two groups. Using multiple linear regression, socio-demographics, lifestyle behaviors, medical, mobility and social factors were examined to identify factors that explained LSM. A qualitative narrative inquiry was completed to augment the findings from the survey; 10 participants with PD were interviewed regarding facilitators and barriers to mobility., Results: The mean overall LSA-composite score for the PD group was 64.2 (SD = 25.8) and 70.3 (SD = 23.1) for the community comparative group (mean difference = 6 points, 95%CI:-0.4, 12.5) indicating most participants moved independently beyond their neighborhoods. A higher proportion of the PD group required assistance with mobility than the community comparison group. Not driving, receiving caregiving, lower social participation, and lower monthly family finances were associated with restricted LSM in the PD group. Data from qualitative interviews supported quantitative findings and offered insights into the features of the built environment that facilitate and restrict mobility., Conclusion: Individual, social and environmental factors are associated with the LSM among persons with PD. Clinicians and policy-makers should include both individual and community-based factors when developing interventions to encourage the LSM of the PD population., (© 2022 International Parkinson and Movement Disorder Society.)

Background: Information concerning clinical presentation, conditions associated with immune-mediated haemolytic anaemia (IMHA) and thrombocytopenia (IMTP) and outcome in equids is lacking. Previous case reports suggest that immune-mediated disease and neoplasia are associated., Objectives: Characterise the clinical presentation, clinicopathologic data, underlying conditions, treatment and outcome of IMHA and IMTP cases in equids. We hypothesise that IMHA with concurrent thrombocytopenia occurs more often than IMHA or IMTP alone, and that neoplasia is commonly associated with these immune diseases and cases frequently have a poor prognosis., Study Design: Retrospective case-control study., Methods: Medical records were reviewed from 1997 to 2016. Twenty-five equids were diagnosed with IMHA, IMTP or IMHA with thrombocytopenia by Coombs test or flow cytometry. Controls were equids presented for nonimmune-mediated disease immediately prior to and after study animals. Fisher's exact test was used to compare between groups for categorical variables (P < .05). Results reported as odds ratios (OR) and 95% confidence intervals (CI). Unpaired t test and Mann-Whitney test were used to compare between groups for continuous variables (P < .05)., Results: Neoplasia incidence was significantly higher in the study population (28%) versus controls (8%) (P = .04). Equids with primary disease were more likely to survive to discharge than equids with secondary disease (8/9 vs 7/16; P = .03; OR = 13.3; 95% CI: 1.3-134.7). Survivors had a significantly lower blood urea nitrogen (BUN) than those that died or were subjected to euthanasia (survivors, 6.1 ± 2.5 mmol/L vs nonsurvivors, 9.9 ± 3.1 mmol/L P = .003). The odds of short-term mortality were higher in horses presenting with increased BUN (OR = 19.5; 95% CI, 1.8-214.1; P = .009)., Main Limitations: Retrospective nature of the study, small case numbers and limited long-term follow-up., Conclusions: Primary IMHA/IMTP cases have a reasonable prognosis and warrant treatment. Secondary cases have a poor prognosis, and are frequently associated with cancer. BUN may have utility as a prognostic indicator for IMHA/IMTP cases., (© 2020 EVJ Ltd.)

Objective: To assess the relationship between patients' expectations for total knee arthroplasty (TKA) and satisfaction with surgical outcome., Methods: This prospective cohort study recruited patients with knee osteoarthritis (OA) ages ≥30 years who were referred for TKA at 2 hip/knee surgery centers in Alberta, Canada. Those who received primary, unilateral TKA completed questionnaires pre-TKA to assess TKA expectations (17-item Hospital for Special Surgery [HSS] TKA Expectations questionnaire) and contextual factors (age, sex, Western Ontario and McMaster Universities Osteoarthritis Index pain score, Knee Injury and Osteoarthritis Outcome Score physical function short form [KOOS-PS], 8-item Patient Health Questionnaire depression scale, body mass index [BMI], comorbidities, and prior joint replacement), and 1-year post-TKA to assess overall satisfaction with TKA results. Using multivariate logistic regression, we examined the relationship between TKA expectations (HSS TKA outcomes considered to be very important) and postoperative satisfaction (very satisfied versus somewhat satisfied versus dissatisfied). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated., Results: At 1 year, 1,266 patients with TKA (92.1%) reported their TKA satisfaction (mean ± SD age 67.2 ± 8.8 years, 60.9% women, and mean BMI 32.6 kg/m 2 ); 74.7% of patients were very satisfied, 17.1% were somewhat satisfied, and 8.2% were dissatisfied. Controlling for other factors, an expectation of TKA to improve patients' ability to kneel was associated with lower odds of satisfaction (adjusted OR 0.725 [95% CI 0.54-0.98]). An expectation of TKA to improve psychological well-being was associated with lower odds of satisfaction for individuals in the lowest tertile of pre-TKA KOOS-PS scores (adjusted OR 0.49 [95% CI 0.28-0.84]), but higher odds for those in the highest tertile (adjusted OR 2.37 [95% CI 1.33-4.21])., Conclusion: In patients with TKA, preoperative expectations regarding kneeling and psychological well-being were significantly associated with the level of TKA satisfaction at 1 year. Ensuring that patients' expectations are achievable may enhance appropriate provision of TKA., (© 2020, American College of Rheumatology.)

Objectives: Zenker's diverticulum is associated with reduced cricopharyngeal compliance and abnormal intrabolus pressure. However, it is unclear how the pharynx compensates for these deficits. Developments in manometric technology have improved our ability to capture pharyngeal pressure events. This study aims to describe the pharyngeal-upper esophageal sphincter (UES) pressure profile during swallowing in patients with Zenker's diverticulum., Methods: High-resolution manometry was performed on 11 patients with symptomatic Zenker's diverticulum and 11 age- and sex-matched healthy controls during 10 mL liquid swallowing tasks. Pharyngeal and UES pressure magnitudes, durations, and integrals were compared between patients and controls using independent t tests. Other manometric parameters, including residual UES pressure at the time of maximum tongue base pressure and pharyngeal-UES pressure gradient, were also evaluated. A case example using three-dimensional high-resolution manometry is presented., Results: Compared with healthy controls, patients with Zenker's diverticulum exhibited pressure abnormalities in the UES region. While baseline and pre-opening maximum pressures were not different, residual pressures were elevated ( P = .001). Pharyngeal-UES pressure gradients did not differ between the two groups., Conclusion: This study used high-resolution manometry to characterize pharyngeal pressure dynamics in patients with Zenker's diverticulum. The changes occurring at the cricopharyngeus appear to result in persistent UES pressurization during UES opening, rather than high tonic resting pressure. Pharyngeal-UES pressure gradients, critical to bolus passage, were also preserved in this patient population., Level of Evidence: 3b., Competing Interests: The authors have no conflicts of interest to declare., (© 2020 The Authors. Laryngoscope Investigative Otolaryngology published by Wiley Periodicals LLC on behalf of The Triological Society.)

Background: Percutaneous vertebroplasty remains widely used to treat osteoporotic vertebral fractures although our 2015 Cochrane review did not support its role in routine practice., Objectives: To update the available evidence of the benefits and harms of vertebroplasty for treatment of osteoporotic vertebral fractures., Search Methods: We updated the search of CENTRAL, MEDLINE and Embase and trial registries to 15 November 2017., Selection Criteria: We included randomised and quasi-randomised controlled trials (RCTs) of adults with painful osteoporotic vertebral fractures, comparing vertebroplasty with placebo (sham), usual care, or another intervention. As it is least prone to bias, vertebroplasty compared with placebo was the primary comparison. Major outcomes were mean overall pain, disability, disease-specific and overall health-related quality of life, patient-reported treatment success, new symptomatic vertebral fractures and number of other serious adverse events., Data Collection and Analysis: We used standard methodologic procedures expected by Cochrane., Main Results: Twenty-one trials were included: five compared vertebroplasty with placebo (541 randomised participants), eight with usual care (1136 randomised participants), seven with kyphoplasty (968 randomised participants) and one compared vertebroplasty with facet joint glucocorticoid injection (217 randomised participants). Trial size varied from 46 to 404 participants, most participants were female, mean age ranged between 62.6 and 81 years, and mean symptom duration varied from a week to more than six months.Four placebo-controlled trials were at low risk of bias and one was possibly susceptible to performance and detection bias. Other trials were at risk of bias for several criteria, most notably due to lack of participant and personnel blinding.Compared with placebo, high- to moderate-quality evidence from five trials indicates that vertebroplasty provides no clinically important benefits with respect to pain, disability, disease-specific or overall quality of life or treatment success at one month. Evidence for quality of life and treatment success was downgraded due to possible imprecision. Evidence was not downgraded for potential publication bias as only one placebo-controlled trial remains unreported. Mean pain (on a scale zero to 10, higher scores indicate more pain) was five points with placebo and 0.7 points better (0.3 better to 1.2 better) with vertebroplasty, an absolute pain reduction of 7% (3% better to 12% better, minimal clinical important difference is 15%) and relative reduction of 10% (4% better to 17% better) (five trials, 535 participants). Mean disability measured by the Roland-Morris Disability Questionnaire (scale range zero to 23, higher scores indicate worse disability) was 14.2 points in the placebo group and 1.5 points better (0.4 better to 2.6 better) in the vertebroplasty group, absolute improvement 7% (2% to 11% better), relative improvement 9% better (2% to 15% better) (four trials, 472 participants).Disease-specific quality of life measured by the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) (scale zero to 100, higher scores indicating worse quality of life) was 62 points in the placebo group and 2.3 points better (1.4 points worse to 6.7 points better), an absolute imrovement of 2% (1% worse to 6% better); relative improvement 4% better (2% worse to 10% better) (three trials, 351 participants). Overall quality of life (European Quality of Life (EQ5D), zero = death to 1 = perfect health, higher scores indicate greater quality of life) was 0.38 points in the placebo group and 0.05 points better (0.01 better to 0.09 better) in the vertebroplasty group, absolute improvement: 5% (1% to 9% better), relative improvement: 18% (4% to 32% better) (three trials, 285 participants). In one trial (78 participants), 9/40 (or 225 per 1000) people perceived that treatment was successful in the placebo group compared with 12/38 (or 315 per 1000; 95% CI 150 to 664) in the vertebroplasty group, RR 1.40 (95% CI 0.67 to 2.95), absolute difference: 9% more reported success (11% fewer to 29% more); relative change: 40% more reported success (33% fewer to 195% more).Low-quality evidence (downgraded due to imprecision and potential for bias from the usual-care controlled trials) indicates uncertainty around the risk estimates of harms with vertebroplasty. The incidence of new symptomatic vertebral fractures (from six trials) was 48/418 (95 per 1000; range 34 to 264)) in the vertebroplasty group compared with 31/422 (73 per 1000) in the control group; RR 1.29 (95% CI 0.46 to 3.62)). The incidence of other serious adverse events (five trials) was 16/408 (34 per 1000, range 18 to 62) in the vertebroplasty group compared with 23/413 (56 per 1000) in the control group; RR 0.61 (95% CI 0.33 to 1.10). Notably, serious adverse events reported with vertebroplasty included osteomyelitis, cord compression, thecal sac injury and respiratory failure.Our subgroup analyses indicate that the effects did not differ according to duration of pain (acute versus subacute). Including data from the eight trials that compared vertebroplasty with usual care in a sensitivity analyses altered the primary results, with all combined analyses displaying considerable heterogeneity., Authors' Conclusions: We found high- to moderate-quality evidence that vertebroplasty has no important benefit in terms of pain, disability, quality of life or treatment success in the treatment of acute or subacute osteoporotic vertebral fractures in routine practice when compared with a sham procedure. Results were consistent across the studies irrespective of the average duration of pain.Sensitivity analyses confirmed that open trials comparing vertebroplasty with usual care are likely to have overestimated any benefit of vertebroplasty. Correcting for these biases would likely drive any benefits observed with vertebroplasty towards the null, in keeping with findings from the placebo-controlled trials.Numerous serious adverse events have been observed following vertebroplasty. However due to the small number of events, we cannot be certain about whether or not vertebroplasty results in a clinically important increased risk of new symptomatic vertebral fractures and/or other serious adverse events. Patients should be informed about both the high- to moderate-quality evidence that shows no important benefit of vertebroplasty and its potential for harm.

Objective: To determine if pattern recognition techniques applied to high-resolution manometry (HRM) spatiotemporal plots of the pharyngeal swallow can identify features of disordered swallowing reported on the Modified Barium Swallow Impairment Profile (MBSImP)., Study Design: Case series evaluating new method of data analysis., Setting: University hospital., Subjects and Methods: Simultaneous HRM and videofluoroscopy was performed on 30 subjects (335 swallows) with dysphagia. Videofluoroscopic studies were scored according to the MBSImP guidelines while HRM plots were analyzed using a novel program. Pattern recognition using a multilayer perceptron artificial neural network (ANN) was performed to determine if 7 pharyngeal components of the MBSImP as well as penetration/aspiration status could be identified from the HRM plot alone. Receiver operating characteristic (ROC) analysis was also performed., Results: MBSImP parameters were identified correctly as normal or disordered at an average rate of approximately 91% (area under the ROC curve ranged from 0.902 to 0.981). Classifications incorporating two MBSImP parameters resulted in classification accuracies over 93% (area under the ROC curve ranged from 0.963 to 0.989)., Conclusion: Pattern recognition coupled with multiparameter quantitative analysis of HRM spatiotemporal plots can be used to identify swallowing abnormalities, which are currently assessed using videofluoroscopy. The ability to provide quantitative, functional data at the bedside while avoiding radiation exposure makes HRM an appealing tool to supplement and, at times, replace traditional videofluoroscopic studies.

Background: Transmission of highly pathogenic avian influenza and the recent pandemic H1N1 viruses to domestic cats and other felids creates concern because of the morbidity and mortality associated with human infections as well as disease in the infected animals. Experimental infections have demonstrated transmission of influenza viruses in cats., Objectives: An epidemiologic survey of feral cats was conducted to determine their exposure to influenza A virus., Methods: Feral cat sera and oropharyngeal and rectal swabs were collected from November 2008 through July 2010 in Alachua County, FL and were tested for evidence of influenza A virus infection by virus isolation, PCR, and serological assay., Results and Conclusions: No virus was isolated from any of 927 cats examined using MDCK cell or embryonated chicken egg culture methods, nor was viral RNA detected by RT-PCR in 200 samples tested. However, 0.43% of cats tested antibody positive for influenza A by commercial ELISA. These results suggest feral cats in this region are at minimal risk for influenza A virus infection., (© 2011 Blackwell Publishing Ltd.)

Background: Cytomegalovirus (CMV) is a herpesvirus and the most common cause of congenital infection in developed countries. Congenital CMV infection can have devastating consequences to the fetus. The high incidence and the serious morbidity associated with congenital CMV infection emphasise the need for effective interventions to prevent the antenatal transmission of CMV infection., Objectives: The aim of this review was to assess the benefits and harms of interventions used during pregnancy to prevent mother to fetus transmission of CMV infection., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2010)., Selection Criteria: All randomised controlled trials (RCTs) and quasi RCTs investigating antenatal interventions for preventing the transmission of CMV from the mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant., Data Collection and Analysis: Two review authors independently assessed studies for inclusion., Main Results: We identified six studies from the search. None of these studies met the pre-defined criteria for inclusion in this review., Authors' Conclusions: To date, no RCTs are available that examine antenatal interventions for preventing the transmission of CMV from the infected mother to fetus during pregnancy and adverse outcomes in the congenitally infected infant. Further research is needed to assess the efficacy of interventions aimed at preventing the transmission of CMV from the mother to fetus during pregnancy including a long-term follow-up of exposed infants and a cost effective analysis.

Background: Herpes simplex virus (HSV) is a rare but serious neonatal pathogen. Prior to the availability of antiviral drugs the mortality associated with all but localised neonatal infection was high, with 85% of infants with disseminated HSV infection and 50% of infants with encephalitis dying by one year of age. The morbidity in the survivors of multiorgan infection was also high, with up to 50% experiencing long-term neurological sequelae., Objectives: To determine the effect of antiviral agents in the treatment of neonatal HSV infections on mortality, progression of disease and neurodevelopmental sequelae at approximately one year. The secondary objective was to assess the effect of antiviral agents on major complications associated with the use of these agents including nephrotoxicity and bone marrow suppression., Search Strategy: Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 4, 2008), MEDLINE (1996 - Nov 2008), EMBASE (1982 - Nov 2008) and reference lists of published trials., Selection Criteria: Randomised and quasi-randomised controlled trials of antiviral therapy in infants less than one month of age with virologically proven HSV infection were included., Data Collection and Analysis: Data were extracted and the analyses performed independently by two review authors. Studies were analysed for methodological quality using the criteria of the Cochrane Neonatal Review Group. All data were analysed using RevMan 5.1. When possible, meta-analysis was performed to calculate typical relative risk, typical risk difference, along with their 95% confidence intervals (CI)., Main Results: Two eligible studies of a total of 273 infants were included. Both studies were randomized controlled trials. One study treated 63 infants with vidarabine or placebo (Whitley 1980) and the other study treated 210 infants with aciclovir or vidarabine (Whitley 1991).In the study comparing vidarabine with placebo (Whitley 1980), infants with all forms of neonatal HSV disease were included [disseminated disease, central nervous system (CNS) disease alone, and skin, eye and mouth (SEM) disease].There was no significant reduction in the risk of mortality when analyzed as an entire group; however, mortality was significantly reduced when data from infants with CNS disease or disseminated disease were combined. There was no difference in the rate of neurological abnormalities in survivors at one year when analyzed as an entire group or by disease category.There was no difference between aciclovir and vidarabine (Whitley 1991) in preventing mortality from neonatal HSV disease, in preventing disease progression, in reducing the incidence of neurological abnormality at one year, or in the incidence of drug-induced renal or bone marrow toxicity. In infants with SEM disease, there was no significant difference in neurological outcome with aciclovir compared vidarabine treatment. Both drugs were well tolerated in the newborn period., Authors' Conclusions: There is insufficient trial evidence to evaluate the effects of antiviral agents with controls or with each other. The rarity of the condition makes effectively powered clinical trials difficult to perform. The efficacy of newer antiviral agents with better bioavailability (e.g. valaciclovir, valganciclovir) for the treatment of neonatal disease needs to be evaluated in randomised trials. The efficacy of oral formulations need to be evaluated as they may be useful for infants with skin, eye or mouth HSV disease or in the treatment of infants with recurrences after the neonatal period.

Background: Cytomegalovirus (CMV) is the most common virus causing disease and death in solid organ transplant recipients during the first six months post-transplant. Previous systematic reviews have demonstrated the efficacy of antiviral medications used prophylactically or pre-emptively in preventing CMV disease. In this review the efficacy of older agents (immunoglobulins (IgG), anti CMV vaccines and interferon) are examined., Objectives: To assess the benefits and harms of IgG, anti CMV vaccines or interferon for preventing symptomatic CMV disease in solid organ transplant recipients., Search Strategy: We searched the Cochrane Renal Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, in The Cochrane Library), MEDLINE, EMBASE, reference lists and abstracts from conference proceedings without language restriction. Date of last search: December 2005, Selection Criteria: Randomised and quasi-randomised controlled trials comparing IgG, anti CMV vaccine or interferon with placebo or no treatment, IgG alone or combined with antiviral medications with antiviral medications or IgG alone in recipients of any solid organ transplant., Data Collection and Analysis: Two of four authors independently assessed trial quality and extracted data from each trial. Statistical analyses were performed using the random effects model and results expressed as relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI)., Main Results: Thirty seven trials (2185 participants) were included in this review. There was no significant difference in the risk for CMV disease (16 trials, 770 patients: RR 0.80, 95% CI 0.61 to 1.05), CMV infection (14 trials, 775 patients: RR 0.94, 95% CI 0.80 to 1.10) or all-cause mortality (8 trials, 502 patients: RR 0.57, 95% CI 0.32 to 1.03) with IgG compared with placebo/no treatment. However IgG significantly reduced the risk of death from CMV disease (6 trials, 346 patients: RR 0.33, 95% CI 0.14 to 0.80). There was no difference in the risk for CMV disease (4 trials, 298 patients: RR 1.17, 95% CI 0.74 to 1.86), CMV infection (4 trials, 298 patients: RR 1.16, 95% CI 0.89 to 1.52) or all-cause mortality (2 trials, 217 patients: RR 0.92, 95% CI 0.37 to 2.29) between antiviral medication combined with IgG and antiviral medication alone. There was no significant difference in the risk of CMV disease with anti CMV vaccine or interferon compared with placebo or no treatment., Authors' Conclusions: Currently there are no indications for IgG in the prophylaxis of CMV disease in recipients of solid organ transplants.

This population-based case-finding study sought to determine asthma prevalence and characterize disease severity and burden among school-aged children in the Little Rock School District. Asthma cases were identified by validated algorithm and parental report of asthma diagnosis. The overall response rate was low. Among schools with greater than 50% response rate, prevalence of physician-diagnosed asthma was comparable to other studies in public school settings. Prevalence of symptoms in cases identified as current is suggestive of poor asthma control. Improved systems for case identification of children with asthma are needed in schools. Efforts should focus on strategies to improve asthma control.

1. The aim of this study was to functionally characterize the recombinant mouse P2X(4) receptor and to compare its pharmacological properties with those of the human and rat orthologues. 2. Whole cell recordings were made from rafts of HEK-293 cells stably expressing recombinant mouse, rat or human P2X(4) receptors, using Cs-aspartate containing electrodes (3 - 8 MOmega) in a HEPES-buffered extracellular medium. 3. The agonist potency of ATP at the three species orthologues was similar, with mean EC(50) values of 2.3 microM, 1.4 microM and 5.5 microM, respectively. 4. Adenosine-5'-tetraphosphate (AP4) acted as a partial agonist with respect to ATP at the mouse and human P2X(4) receptors (EC(50)=2.6 and 3.0 microM), but was significantly less potent at the rat orthologue (EC(50)=20.0 microM). alpha,beta-methylene adenosine-5'-triphosphate (alpha,beta-meATP) also acted as a partial agonist, producing 29% of the maximum response at the mouse P2X(4) and 24% at the human P2X(4) receptor. 5. In contrast to the other species orthologues, alpha,beta-meATP failed to elicit a significant agonist response at rat P2X(4) receptors, and was found to act as an antagonist, with an IC(50) of 4.6 microM, against 10 microM ATP. 6. Mouse P2X(4) receptors were found to be sensitive to the antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (IC(50)=10.5 microM), as were human P2X(4) receptors (IC(50)=9.6 microM). The rat receptor however, showed a low sensitivity to PPADS (IC(50)>100 microM). 7. All three orthologues were relatively suramin-insensitive (IC(50)>100 microM) and insensitive to 1-[N, O-Bis(5-isoquinoline sulphonyl)benzyl]-2-(4-phenylpiperazine)ethyl]-5-isoquinoline sulphonamide (KN-62; IC(50)>3 microM). 8. Our results suggest that the pharmacological properties of the mouse receptor are most similar to the human P2X(4) receptor, and differ markedly from the rat receptor.

The endogenous and lipopolysaccharide stimulated interleukin (IL)-1 beta production in vitro by peritoneal monocytes/macrophages from patients on continuous ambulatory peritoneal dialysis (CAPD) was examined during episodes of infection and inflammation. Measurement of immunoreactive IL-1 beta and bioactive IL-1 in both supernatants and cell lysates after culture for 18 h revealed that these cells secreted a significantly lower proportion of total IL-1 than that measured for elutriated blood monocytes. For the inflammatory peritoneal cells, the proportion of total IL-1 beta that was cell-associated resembled that reported for more differentiated pulmonary alveolar macrophages and for adherent monocytes cultured for 18 h prior to stimulation. A similar reduced ability to secrete IL-1 beta was detected for unfractionated peritoneal cells from CAPD patients without peritonitis upon direct comparison with the IL-1 beta production by blood mononuclear cells from the same patients. These results suggested that at a time when a pro-inflammatory response by extravasated host monocytes/macrophages was required by CAPD patients with peritonitis, only a minor proportion of total IL-1 beta would be available extracellularly. This study highlights the rapidity with which extravasated monocytes lose their ability to secrete IL-1 beta and raises the possibility that an important site of utilization of IL-1 beta in vivo may be intracellular in its location.

Plasmid plJ303 stability in Streptomyces lividans cultures has been studied by measuring plasmid copy number under various growth conditions. An increase in mean plasmid copy number was normally seen during early rapid growth in both shaken culture and stirred vessel fermentations at 28 degrees C. Maximum copy numbers were consistently attained in early stationary phase followed by a decline (of variable amount) upon further incubation. The imposition of environmental stress (high growth temperature, i.e., 37 degrees C, and low dissolved oxygen tension, i.e., <5% air saturation) led to a plasmid copy number of zero and a 50% reduction, respectively. Interestingly, the relative proportions of plasmid topoisomers changed with time since progressively more supercoiled forms were observed throughout the stationary phase. Plasmid dimers were also observed in some cultures, and no evidence of structural plasmid instability was found. In general, this host-vector system seemed remarkably stable under normal growth conditions. However, copious organic acid production by the host was observed and was thought to be undesirable for good heterologous gene expression of a secreted protein.

1 The peripheral and central activities of tamoxifen were studied in the ovariectomized adult rat, up to 16 d after a single dose of 7.0 or 0.7 mg/kg. 2 Food consumption and body weight were decreased; only food consumption returned to control values after 16 d. 3 The weights of the uterus and of the uterine luminal fluid were increased for up to 8 d. 4 Serum follicle-stimulating hormone (FSH) concentrations decreased, but only significantly 1 and 8 d after 7.0 mg tamoxifen/kg. Serum luteinizing hormone (LH) and prolactin concentrations were elevated for up to 4 d. 5 Lordosis behaviour was absent throughout the period studied. 6 Within 3 d of administration, tamoxifen partially antagonized the oestrogen-induced changes in uterine luminal fluid, prolactin and LH secretion and lordosis behaviour. 7 Tamoxifen did not alter oestrogen-induced changes in uterine weight, food consumption and body weight. 8 The experiments demonstrate that tamoxifen is active for up to 16 d after a single intraperitoneal dose; oestrogen agonist, partial agonist and antagonist activities were demonstrated. The duration and type of activity depends upon the dose of tamoxifen and the target tissue response examined.