Chlamydia gallinacea: a widespread emerging Chlamydia agent with zoonotic potential in backyard poultry.

Chlamydia gallinacea, a new chlamydial agent, has been reported in four European countries as well as Argentina and China. Experimentally infected chickens with C. gallinacea in previous study showed no clinical signs but had significantly reduced gains in body weight (6·5-11·4%). Slaughterhouse workers exposed to infected chickens have developed atypical pneumonia, indicating C. gallinacea is likely a zoonotic agent. In this study, FRET-PCR confirmed that C. gallinacea was present in 12·4% (66/531) of oral-pharyngeal samples from Alabama backyard poultry. Phylogenetic comparisons based on ompA variable domain showed that 16 sequenced samples represented 14 biotypes. We report for the first time the presence of C. gallinacea in North America, and this warrants further research on the organism's pathogenicity, hosts, transmission, and zoonotic potential.

Development of MAPT S305 mutation models exhibiting elevated 4R tau expression, resulting in altered neuronal and astrocytic function.

Due to the importance of 4R tau in the pathogenicity of primary tauopathies, it has been challenging to model these diseases in iPSC-derived neurons, which express very low levels of 4R tau. To address this problem we have developed a panel of isogenic iPSC lines carrying the MAPT splice-site mutations S305S, S305I or S305N, derived from four different donors. All three mutations significantly increased the proportion of 4R tau expression in iPSC-neurons and astrocytes, with up to 80% 4R transcripts in S305N neurons from as early as 4 weeks of differentiation. Transcriptomic and functional analyses of S305 mutant neurons revealed shared disruption in glutamate signaling and synaptic maturity, but divergent effects on mitochondrial bioenergetics. In iPSC-astrocytes, S305 mutations induced lysosomal disruption and inflammation and exacerbated internalization of exogenous tau that may be a precursor to the glial pathologies observed in many tauopathies. In conclusion, we present a novel panel of human iPSC lines that express unprecedented levels of 4R tau in neurons and astrocytes. These lines recapitulate previously characterized tauopathy-relevant phenotypes, but also highlight functional differences between the wild type 4R and mutant 4R proteins. We also highlight the functional importance of MAPT expression in astrocytes. These lines will be highly beneficial to tauopathy researchers enabling a more complete understanding of the pathogenic mechanisms underlying 4R tauopathies across different cell types.

The responses of professional groups to the use of Section 136 of the Mental Health Act (1983, as amended by the 2007 Act) in Gloucestershire.

BACKGROUND: Section 136 (S136) of the Mental Health Act (1983, as amended by the 2007 Act) empowers the police to detain those suspected of being mentally disordered in a public place and to convey them to a place of safety (POS) for further assessment. Gloucestershire has not had a specialist facility for S136 detentions and individuals were taken to the police cells or occasionally A&E departments for assessment. AIMS: This paper forms one part of three aspects under investigation. Two companion papers by the authors describe the use of S136 using anonymised audit data and the experiences of detainees. The objectives of this paper have been to assess the responses of the different professional groups involved in the process of S136. METHOD: An anonymous postal questionnaire was distributed to eight groups of professionals who were identified as having the potential to be involved in part of the process of a S136 detention. Results were collated and analysed, and formed the basis for a series of follow-up focus groups within groups to explore themes that warranted further investigation. RESULTS: An overall response rate of 59% was achieved. Seventy-four per cent of participants thought that there should be an alternative POS to the police station. A&E was thought to be an unsuitable alternative POS, with a psychiatric hospital being the first choice for 58%. CONCLUSIONS: There is a gap in the expectations of the different agencies involved in the S136 process, which have the potential to be divisive if interagency pathways and agreements are not in place.

The use of Section 136 (Mental Health Act 1983) in Gloucestershire.

The small number of published studies on the use of Section 136 (S136) of the Mental Health Act 1983 may reflect neither the current situation nor the true national picture as most of the research comes from large urban centres and was published before 1997. We studied the use of S136 between 2002 and 2006 in Gloucestershire, a rural English county with a population of approximately 585,000, by analysing data held by the police and local mental health services. On average 192 subjects (range 176-203) were detained each year under S136, equating to a population rate of 32.8 S136 detentions per 100,000 per year in Gloucestershire. In contrast to other published studies, ethnic minorities, particularly Afro-Caribbean males, were overrepresented only in a minor way. Of those individuals detained, about a third were admitted, a lower rate than in other studies. Acts or threats of self-harm were common (55%), but acts or threats of violence (28%) and evidence of intoxication (16%) were present in a minority, suggesting that detainees are more likely to pose a risk to themselves than others.

A pilot evaluation of saline sonohysterography for postmenopausal bleeding with thickened endometrium.

The aim of this study was to assess the clinical and cost implications of pilot introduction of saline sonohysterography for postmenopausal bleeding with thickened endometrium (>or= 5 mm), at the Royal Glamorgan Hospital. The investigation was attempted in 48 patients who were found to have a thickened endometrium (>or= 5 mm) on transvaginal ultrasound scanning. The attempt was successful in 45 patients (93.8%). Failures were due to (1) cervical stenosis and (2) leakage of saline from the cervix. Difficult catheterisation of the cervix causing pain was encountered in a minority of cases. Two-thirds of patients were found have focal lesions and were booked for hysteroscopic resection. These patients included 30 with polyps, which were precisely described in all of them. In view of this low complication rate and high accuracy, the technique was integrated as a standard method of investigation for postmenopausal bleeding at the hospital.

Solution structure and peptide binding of the SH3 domain from human Fyn.

BACKGROUND: The Src family of tyrosine kinases is involved in the propagation of intracellular signals from many transmembrane receptors. Each member of the family contains two domains that regulate interactions with other molecules, one of which is the Src homology 3 (SH3) domain. Although structures have previously been determined for SH3 domains, and ideas about peptide-binding modes have been proposed, their physiological role is still unclear. RESULTS: We have determined the solution structure of the SH3 domain from the Src family tyrosine kinase Fyn in two forms: unbound and complexed with a peptide corresponding to a putative ligand sequence from phosphatidylinositol 3' kinase. Fyn SH3 shows the typical SH3 topology of two perpendicular three-stranded beta sheets and a single turn of 3(10) helix. The interaction of SH3 with three potential ligand peptides was investigated, demonstrating that they all bind to the same site on the molecule. A previous model for ligand binding to SH3 domains predicts binding in one of two orientations (class I or II), each characterized by a consensus sequence. The ligand with the closest match to the class I consensus sequence bound with highest affinity and in the predicted orientation. CONCLUSIONS: The Fyn SH3 domain has a well-defined structure in solution. The relative binding affinities of the three ligand peptides and their orientation within the Fyn SH3 complex were consistent with recently proposed models for the binding of 'consensus' polyproline sequences. Although the affinities of consensus and non-consensus peptides are different, the degree of difference is not very large, suggesting that SH3 domains bind to polyproline peptides in a promiscuous manner.

A rare case of primary epithelioid angiosarcoma of the ureter.

Angiosarcoma is an extremely rare vascular malignancy with a 1-year survival rate of 50%, regardless of tumour origin. Distant metastases are common and occur in the lungs, bone, lymph nodes and soft tissues. The majority of patients with angiosarcoma present with localised disease, although 25-45% have distant metastases at presentation. There are few reported cases of angiosarcomas of the bladder and we report the second case in the literature of primary angiosarcoma of the ureter. We suggest that, in atypical manifestations of suspected urothelial malignancy, the multidisciplinary team considers the possibility of rarer, aggressive tumours early. This may influence clinical decision making towards offering radical treatments earlier, before it is too late to do so owing to aggressive oncological behaviour.

Combining tricyclic and monoamine oxidase inhibitor antidepressants.

The charts of 150 inpatients and 51 outpatients treated with a monoamine oxidase inhibitor (MAOI)-tricyclic antidepressant combination were reviewed. The incidence and severity of side effects among the patients on the combined regimen were essentially the same as those seen in the control groups. There were no deaths or strokes resulting from use of this regimen. The most frequent troublesome side effect was orthostatic hypotension. We conclude that the use of a MAOI-tricyclic combination in oral therapeutic doses is safe. However, the efficacy of this combination has not yet been proved, and it may be particularly toxic if taken in an overdose.

Clinical significance of the V wave in the main pulmonary artery.

Among 68 patients with mitral insufficiency who had right and left cardiac catheterization and left ventriculography, 6 had retrograde transmission of the left atrial V wave into the main pulmonary artery. All of these patients had mitral insufficiency of acute onset. The remaining 62 patients had chronic mitral insufficiency that was considered severe in 17. Pulmonary vascular resistance was lower in the group with acute insufficiency (mean 139 dynes sec cm-5) than in the group with chronic severe insufficiency (mean 631 dynes cm-5) (P less than 0.005). Nondistensibility of the left atrium and low pulmonary vascular resistance were the two factors favoring retrograde transmission of V waves. Because both factors are present in acute mitral regurgitation, this finding is helpful in differentiating patients with acute mitral insufficiency.

Tamoxifen inhibition of an in vitro oestradiol-induced surface coat change on mouse blastocysts.

1. Eighty-nine hour post-coitus mouse blastocysts cultured in the presence of oestradiol-17beta underwent a histochemically detectable surface coat change. 2. Tamoxifen was found to inhibit this in vitro-induced change. The role of Tamoxifen as an inhibitor of implantation is discussed.

Developmental delay, short stature, and minor facial anomalies in a child with ring chromosome 16.

We present a girl with ring chromosome 16. Clinical abnormalities included developmental delay, short stature, and minor facial anomalies. Analysis of the glutamate-pyruvate transaminase (GPT) phenotype suggests the possible exclusion of the GPT locus expressed in erythrocytes (GPT) from the very distal p13 region of chromosome 16.

Right atrial mass biopsy guided by transesophageal echocardiography.

A 69-year-old woman was found to have a right atrial mass on transthoracic echocardiogram. Biopsy of the mass was performed using transesophageal echocardiography for visual guidance. Pathologic study revealed an organizing thrombus. This case illustrates the clinical utility of transesophageal echocardiography in the biopsy of right atrial masses.

Progression of aortic stenosis.

We assessed progressive stenosis of the aortic valve in 11 adult patients (mean age of 48 years) with aortic stenosis who had undergone two cardiac catheterizations without intervening aortic valve surgery. The mean time between cardiac catheterization was 59 months (range 20 to 133). No patients had mitral valve disease. Two patients had coronary artery disease. The results showed that progressive stenosis of the aortic valve occurred in 10 of 11 patients with a significant decrease in the calculated mean aortic valve area from 1.2 +/- 0.2 sq cm to 0.7 +/- 0.1 sq cm (P less than 0.005); a significant increase in mean left ventricular peak systolic pressure from 149 +/- 8 mm Hg to 199 +/- 3 mm Hg (P less than 0.01), and a significant increase in mean left ventricular aortic pressure gradient from 31 +/- 4 mm Hg to 75 +/- 13 mm Hg (P less than 0.005). On an individual basis, the change in left ventricular pressure and the left ventricular-aortic gradient did not always reflect the decrease in aortic valve area because of variations in cardiac output. The shortest period of time in which progression of aortic stenosis occurred was 27 to 29 months. Thus, progressive stenosis of the aortic valve occurs in adults with isolated aortic valvular stenosis. Significant decrease in the aortic valve area can develop in as short a period as 27 to 29 months.

Left ventricular function and coronary obstruction as predictors of survival following aorta-coronary bypass.

A retrospective analysis was undertaken of clinical data and catheterization studies of 151 consecutive unselected patients who underwent aorta-coronary bypass at the University of Kansas Medical Center between 1971 and 1973. The purpose was to determine the effect of preoperative left ventricular function and extent and severity of coronary artery obstruction on operative mortality rate and long-term survival. The postoperative follow-up period ranged from 10 to 49 months and averaged 26 months. Left ventricular function was assessed by qualitative analysis of left ventricular angiograms. Severity of coronary obstruction was quantified by scoring coronary arteriograms according to the system of Friesinger and associates. Patients with normal or near normal ventriculograms were considered to have good left ventricular function. Patients showing moderate or severe impairment of contraction were considered to have poor left ventricular function. Obstruction scores ranging from 2 to 7 points were classified as low scores, and scores from 8 to 15 points were classified as high scores. Four groups of patients were identified based upon preoperative left ventricular function and obstruction severity: Group I, 29 patients with good left ventricular function and low scores; Group II, 22 patients with poor left ventricular function and low scores. Group III, 28 patients with good left ventricular function and high scores. Elective aorta-coronary bypass in these three groups was accompanied by no operative or late deaths. Group IV comprised 72 patients with poor left ventricular function and high scores. In this group there was a 10 per cent operative mortality rate (7 of 72 patients) and a 5 per cent year late mortality rate. Relief of angina occurred equally in all groups. Thus operative risk can be prospectively determined by analysis of left ventricular function and severity of coronary obstruction. Surgical treatment resulted in negligible operative and late mortality rates (0 per cent) in all patients except those in whom poor ventricular function was accompanied by severe and diffuse coronary artery obstruction. Operation should be offered to this latter group (Group IV) despite the higher operative and postoperative risk because of salutary postoperative results.

Swallowing dysfunction after cardiac operations. Associated adverse outcomes and risk factors including intraoperative transesophageal echocardiography.

The frequency, importance to patient outcomes, and independent predictors of postoperative swallowing dysfunction documented by barium cineradiography were examined in 869 patients undergoing cardiac operations over a 12-month period. Swallowing dysfunction was diagnosed in 34 patients (4% incidence) and was associated with documented pulmonary aspiration in 90% of these patients, increased frequency of pneumonia (p < 0.0001), need for tracheostomy (p = 0.0002), length of stay in the intensive care unit (p = 0.0001), and duration of hospitalization after the operation (p = 0.0001). Independent predictors of postoperative swallowing dysfunction determined by multivariate logistic regression included age (p < 0.001), length of tracheal intubation after the operation (p = 0.001), and intraoperative use of transesophageal echocardiography (p = 0.003). Dysfunctional swallowing after cardiac operations, a serious complication significantly related to postoperative respiratory morbidity and extended length of hospitalization, is more common in older patients. An association between intraoperative use of transesophageal echocardiography and swallowing dysfunction was also observed in our patients.

Multiple evanescent white dot syndrome. II. Electrophysiology of the photoreceptors during retinal pigment epithelial disease.

We performed electrophysiologic studies of photoreceptor function in three patients with multiple evanescent white dot syndrome. During the acute stage, while the visual acuity was impaired, the electroretinogram (ERG) a-wave and the early receptor potential (ERP) amplitudes were profoundly decreased. The ERP regeneration times, determined for one subject, were prolonged. These findings suggest that photoreceptor function was impaired (abnormal a-wave), the effective visual pigment optical density of the outer segments was markedly reduced (ERP amplitude), and visual pigment regeneration was abnormal (ERP regeneration kinetics). During the recovery stage, the ERG and ERP amplitudes and visual acuity returned to normal. Our patients' disease seemed to be primarily of the retinal pigment epithelium (RPE). The decreased visual pigment density and prolonged regeneration kinetics emphasize the physiologic dependence of the sensory retina on the RPE.

Multiple evanescent white dot syndrome. I. Clinical findings.

We examined 11 young patients with unilateral ocular findings that included multiple white dots at the level of the retinal pigment epithelium (RPE) or the deep retina, vitreal cells, RPE granularity in the macula, reduced visual acuity, electroretinogram (ERG) and early receptor potential (ERP) amplitudes, and fluorescein leakage from disc capillaries and late staining of the RPE. Recovery of visual function included a dramatic improvement in ERG and ERP amplitudes over several weeks. The etiology of this syndrome remains uncertain; there is no definite evidence of systemic involvement.

The effect of tamoxifen on the in vitro production of prostaglandins F by the guinea pig uterine tissue.

Tamoxifen, a drug widely known as an antioestrogen is shown to depress the in vitro yield of PGF from pro-oestrus guinea pig uterine homogenates. The possibility that this is a novel antioestrogenic effect of tamoxifen is discussed.

The EU precautionary bans of animal feed additive antibiotics.

Toxicologists, with good reason, will feel that the biological safety of chemical products across the market sectors rests largely on their efforts. However, one sector has received much adverse attention from the media, consumers, politicians, legislators and advisory groups in recent years. It is food animal production in intensive systems and, within those, various types of chemical additives included in the compound diets fed. No additive class received more adverse comment than those antibiotics used for the purpose of enhancing the efficiency of animal production. This paper considers the safety of the antibiotic feed additives (AFAs) against the background of the regulatory measures in place, defines their role and describes the relevant concerns. It closes with comment on the microbiologically-based health risk which underpinned the AFA bans and sounds a warning over the precedent created by the use of the precautionary principle in the recent banning of six of their number.

Isolation, synthesis, and pharmacology of metabolites of 1-(3,4-dichlorobenzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidone.

The metabolism of 1-(3,4-dichlorobenzyl)-3,4,5,6-tetrahydro-2(1H)-pyrimidone, an antianxiety/antidepressant agent, in dogs is reported. Two metabolites, 3-[1-(3,4-dichlorobenzyl)-1-ureido]propanoic acid and 1-(3,4-dichlorobenzyl)uracil, were isolated, characterized, and synthesized. Neither metabolite was acutely toxic, and they did not exhibit antidepressant or antianxiety/anticonvulsant activity.