Functionalized silver nanoparticles depress aerobic metabolism in the absence of overt toxicity in brackish water killifish, Fundulus heteroclitus.

Engineered nanomaterials (ENMs) tend to precipitate in saline waters so the majority of aquatic toxicity studies have focused on freshwaters, where bioavailability is presumed to be higher. Recent studies have illustrated that some ENM formulations are bioavailable and bioactive in salt water and that their effects are more pronounced at the physiological than biochemical level. These findings raise concerns regarding the effects of ENMs on marine organisms. Therefore, our goal was to characterize the effects of polyvinylpyrolidone-functionalized silver ENMs (nAg) on aerobic performance in the killifish (Fundulus heteroclitus), a common euryhaline teleost. Fish were exposed to 80 µg L-1 of 5 nm nAg for 48 h in brackish water (12 ppt) and routine (MO2min) and maximum (MO2max) rates of oxygen consumption were quantified. Silver dissolution was minimal and nAg remained well dispersed in brackish water, with a hydrodynamic diameter of 21.0 nm, compared to 19.3 in freshwater. Both MO2min and MO2max were significantly lower (by 53 and 30%, respectively) in killifish exposed to nAg and a reduction in MO2 variability suggested spontaneous activity was suppressed. Neither gill Na+/K+-ATPase activity, nor various other biochemical markers were affected by nAg exposure. The results illustrate that a common ENM formulation is bioactive in salt water and, as in previous studies on functionalized copper ENMs, that effects are more pronounced at the whole animal than the biochemical level.

Analysis of exome sequence in 604 trios for recessive genotypes in schizophrenia.

Genetic associations involving both rare and common alleles have been reported for schizophrenia but there have been no systematic scans for rare recessive genotypes using fully phased trio data. Here, we use exome sequencing in 604 schizophrenia proband-parent trios to investigate the role of recessive (homozygous or compound heterozygous) nonsynonymous genotypes in the disorder. The burden of recessive genotypes was not significantly increased in probands at either a genome-wide level or in any individual gene after adjustment for multiple testing. At a system level, probands had an excess of nonsynonymous compound heterozygous genotypes (minor allele frequency, MAF ⩽ 1%) in voltage-gated sodium channels (VGSCs; eight in probands and none in parents, P = 1.5 × 10(-)(4)). Previous findings of multiple de novo loss-of-function mutations in this gene family, particularly SCN2A, in autism and intellectual disability provide biological and genetic plausibility for this finding. Pointing further to the involvement of VGSCs in schizophrenia, we found that these genes were enriched for nonsynonymous mutations (MAF ⩽ 0.1%) in cases genotyped using an exome array, (5585 schizophrenia cases and 8103 controls), and that in the trios data, synaptic proteins interacting with VGSCs were also enriched for both compound heterozygosity (P = 0.018) and de novo mutations (P = 0.04). However, we were unable to replicate the specific association with compound heterozygosity at VGSCs in an independent sample of Taiwanese schizophrenia trios (N = 614). We conclude that recessive genotypes do not appear to make a substantial contribution to schizophrenia at a genome-wide level. Although multiple lines of evidence, including several from this study, suggest that rare mutations in VGSCs contribute to the disorder, in the absence of replication of the original findings regarding compound heterozygosity, this conclusion requires evaluation in a larger sample of trios.

Newborn hearing screening: a regional example for national care.

Congenital Permanent Childhood Hearing Impairment (PCHI) is known to have a negative effect on language acquisition, cognitive development and social integration. Since 2000 our department has implemented a UNHS program in the West of Ireland. We describe our experience and detail our results to date. All neonates born from October 2000 to November 2007 were screened using a 2-stage protocol. Transient evoked oto-acoustic emissions (TEOAEs) were used to screen all neonates, followed by automated auditory brainstem response (AABR) in those who did not pass TEOAE, and all neonates at audiological risk. 26,281 babies were born over the eight year period. 25,742 underwent the screening process, achieving a coverage rate of 98%. The prevalence of PCHI in the population tested was 1.21/1000 live births (31/25,731). Our results show that a hospital based 2-stage UNHS protocol using TEOAEs and AABR is accurate, feasible and effective.

Oral ulceration--the importance of biopsy.

Pemphigus vulgaris is a rare cause of oral ulceration. A 34 year old male presented with a three week history of severe oral ulceration which was initially treated as aphthous ulceration. However, he failed to improve and a mucosal biopsy was performed. Histology and immunostaining confirmed pemphigus vulgaris.

Incidence of symptomatic toxoplasma eye disease: aetiology and public health implications.

Ocular disease is the commonest disabling consequence of toxoplasma infection. Incidence and lifetime risk of ocular symptoms were determined by ascertaining affected patients in a population-based, active reporting study involving ophthalmologists serving a population of 7.4 million. Eighty-seven symptomatic episodes were attributed to toxoplasma infection. Bilateral visual acuity of 6/12 or less was found in seven episodes (8%) and was likely to have been transient in most cases. Black people born in West Africa had a 100-fold higher incidence of symptoms than white people born in Britain. Only two patients reported symptoms before 10 years of age. The estimated lifetime risk of symptoms in British born individuals (52% of all episodes) was 18/100000 (95% confidence interval: 10.8-25.2). The low risk and mild symptoms in an unscreened British population indicate limited potential benefits of prenatal or postnatal screening. The late age at presentation suggests a mixed aetiology of postnatally acquired and congenital infection for which primary prevention may be appropriate, particularly among West Africans.

Retinochoroiditis is induced by oral administration of Toxoplasma gondii cysts in the hamster model.

Administration of Toxoplasma cysts by intraperitoneal innoculation in the Syrian Golden Hamster provides a reproducible animal model of acquired Toxoplasmic retinochoroiditis and cysts are observed in the brain. However, toxoplasmosis is frequently acquired by oral ingestion of contaminated foodstuffs and it is recognised that the route by which disease is acquired may influence its pathogenesis and clinical expression. This study aimed to determine whether retinochorioiditis and cysts in the brain develop after oral ingestion in the Syrian Golden Hamster model as this is the route of induction akin to that in man and may therefore be more relevant in the study of disease pathogenesis. All animals developed disease by 4 weeks. Ocular and cerebral inflammation was confirmed by histology at 16 weeks and this was milder than in the original model.

Choroidal tuberculosis diagnosed by polymerase chain reaction. A clinicopathologic case report.

PURPOSE: To show the use of the polymerase chain reaction (PCR) in a granulomatous choroidal lesion to support a diagnosis of tuberculosis. DESIGN: Observational case report. TESTING: Nucleic acid target amplification of a choroidal specimen using PCR for detection of Mycobacterium tuberculosis was tested. MAIN OUTCOME MEASURES: Positive nucleic acid target amplification for M. tuberculosis in the ocular sample was measured. RESULTS: PCR was positive for M. tuberculosis with appropriate negative controls. CONCLUSIONS: PCR was thought to be a useful supportive technique in the diagnosis of choroidal tuberculosis.

Congenital vascular anomalies and persistent respiratory symptoms in children.

Congenital cardiovascular anomalies are a rare but treatable cause of stridor in the paediatric population. Despite this, we and the authors of other series have found a delay in referral for endoscopic diagnosis. The duration of symptoms prior to endoscopic diagnosis ranged from 6 weeks to 10 years. It has been estimated that up to 3% of the population have congenital anomalies of the aortic arch complex and we feel that many patients currently being diagnosed as having recurrent croup or atypical asthma must be excluded from this group. We had 16 cases of congenital vascular anomalies causing tracheobronchial compression. Fifteen were due to innominate artery compression and one was due to a double aortic arch. Presenting symptoms included stridor (100%), persistent cough (75%), chronic dyspnoea (75%), reflex apnoea (60%), recurring respiratory tract infections (56%) and dysphagia (25%). Direct laryngoscopy and bronchoscopy was diagnostic in all cases and is our investigation of choice. Eleven underwent aortopexy (69%), one had division of the non-dominant aortic arch (6%) and four were managed conservatively (25%). They were followed for up to 9 years post-operatively and 75% had complete resolution of their symptoms. We feel that only a high clinical index of suspicion will enable these potentially fatal anomalies to be diagnosed.

Effects of drug therapy on Toxoplasma cysts in an animal model of acute and chronic disease.

PURPOSE: To evaluate the effects of drug therapy on the clinical course of acute acquired Toxoplasma retinochoroiditis and on the number of Toxoplasma cysts present in the brain and ocular tissues in the hamster animal model. METHODS: The Syrian golden hamster animal model of Toxoplasma retinochoroiditis was used. In acute disease, systemically administered atovaquone was compared with conventional therapies (pyrimethamine combined with sulfadiazine; clindamycin; and spiramycin). The clinical course of the ocular disease was determined with retinal examination and photography of the fundus. The number of Toxoplasma cysts remaining after treatment was evaluated in aliquots of brain homogenate and in retinal tissue. The effect of atovaquone on cerebral Toxoplasma cyst count was also studied in chronic disease. RESULTS: None of the drugs administered altered the course of the acute disease, judged by clinical examination. Atovaquone alone significantly reduced the number of cerebral Toxoplasma cysts after acute disease. Atovaquone also significantly reduced the cerebral Toxoplasma cyst count in chronic disease. CONCLUSIONS: Tissue cysts are believed to be responsible for reactivation of Toxoplasma retinochoroiditis. Atovaquone has the potential to reduce the risk of recurrent disease.

Lymphocyte subsets in conjunctival mucosa-associated-lymphoid-tissue after exposure to retinal-S-antigen.

PURPOSE: To evaluate the immune cell subsets in conjunctival mucosa-associated-lymphoid-tissue (C-MALT) following challenge with antigen. METHODS: Ten adult female Lewis rats were studied. Five rats received one drop (5 microL) of retinal S-antigen (500 microg/mL in phosphate buffered saline, PBS) instilled into the lower fornix twice daily for 10 consecutive days. Five rats received PBS only and served as controls for the experiment. Two days after the last instillation the animals were sacrificed and the orbital contents prepared for immunohistological staining. A panel of monoclonal antibodies was used: CD5, CD4, CD8, CD25, and CD45RA. The number of positive cells were counted in sections of epibulbar, forniceal, and tarsal conjunctiva. RESULTS: There was a significant increase in the number of CD8+ T lymphocytes in the conjunctiva of animals receiving retinal S-antigen when compared to control animals. CONCLUSION: Conjunctival instillation of retinal S-antigen causes an immune response in the C-MALT with a significant increase in the CD8+ T lymphocyte subset in this tissue. This response may be involved in the induction of tolerance to the encountered antigen.

Phenotypic analysis of resident lymphoid cells in the conjunctiva and adnexal tissues of rat.

The conjunctival associated lymphoid tissue is considered to be an integral part of the mucosal immune system. Under normal circumstances immune mechanisms in mucosal associated lymphoid tissue of the gut and bronchus can selectively suppress, rather than enhance, immune responsiveness to encountered antigens, inducing a state of tolerance. It is possible that conjunctival associated lymphoid tissue can also induce a state of tolerance to encountered antigens. Such a response may be exploited to modulate immune mediated ocular disease. Enhanced tolerance may protect the host against foreign antigen. Alternatively, under certain circumstances when the normal immune system is altered or disrupted the mucosal tissue may act to induce sensitisation and trigger immune mediated disease. The rat is frequently used as an animal model of immune mediated eye disease, but the normal profile of immune cells in the rat conjunctiva has not been studied. This information is essential for meaningful interpretation in the experimental situation. In this study we examined the immunophenotype of lymphoid tissue associated with the conjunctiva, lacrimal gland and Harderian gland of the Lewis rat. CD4+, Ia+ and the monocyte/macrophage population of cells were found predominantly in the substantia propria of the conjuctiva and interstitial connective tissue of the glands. CD8+ cells were distributed mainly in relation to the conjunctival and glandular epithelium. Goblet cells stained strongly with the monoclonal antibody (MAb) MRC OX-39, which is a marker for IL-2 receptors. The overall pattern of distribution of immunocompetent cells in the rat was found to be similar to that reported in humans.

The sphenoidal sinus in optic nerve decompression.

Surgical decompression of the orbit may be necessary in dysthyroid patients with compressive optic neuropathy. Two-wall decompression with a trans-antral or a trans-conjunctival approach is commonly used. However, in some patients the initial improvement following this surgical procedure is not maintained. Although this may be due to disease progression, a variant of orbital anatomy can contribute to sub-optimal decompression. We report three cases in which recurrence of compressive optic neuropathy occurred following two-wall decompression. The sphenoidal sinus was placed anteriorly in these patients. Further decompression which included the lateral wall of the sphenoidal sinus resulted in improvement. An endoscopic approach provides superior access and visibility for decompression of the optic nerve into the sphenoidal sinus, and this approach may be the surgical treatment of choice in these cases.

The effect of tonsillectomy on eustachian tube function.

A two-part study was designed to investigate the effect of tonsillectomy on eustachian tube function and to identify if any change is related to postoperative pain. Middle ear pressure was measured by tympanometry and results were classified as type A (+50 daPa to -99 daPa), type B (flat) or type C (-100 daPa to -350 daPa). Thirty-one patients with type A tympanograms, undergoing tonsillectomy enrolled in study A. Patients had tympanometry the next day and filled in a questionnaire incorporating visual analogue pain scores. In study B, 30 patients underwent a similar protocol and were followed up at 1 week tympanometry and a questionnaire. A control group of 26 patients undergoing appendicectomy was recruited. Follow-up was available on 23 patients from study B. Combining A and B, on the first postoperative day 39% of patients developed type C tympanograms. No member of the control group developed any change in middle ear pressure. There was no significant relationship between pain scores for throat pain or otalgia and the development of negative middle ear pressure. By day 7 all patients had type A tympanograms. Otalgia was a delayed symptom significantly associated with increased throat pain. Transient negative middle ear pressure commonly occurs following tonsillectomy.

A prospective study of acid reflux and globus pharyngeus using a modified symptom index.

Previous authors have demonstrated an association between gastro-oesophageal reflux and globus pharyngeus. With the advent of 24-h pH monitoring the strength of this association has been questioned. A prospective study was performed using a 'Symptom Index' of acid reflux. A positive result was recorded when one out of two globus sensations occurred with acid reflux. The symptom index was assessed prospectively in 21 patients with a history of globus pharyngeus. In eight patients with significant acid reflux as defined by standard pH criteria the symptom index was positive in all cases. The remaining 13 patients had no objective evidence of significant reflux and the symptom index was negative. The symptom index is a useful additional marker to determine the significance of acid reflux in the pathogenesis of globus pharyngeus.

Acquired retinochoroiditis in hamsters inoculated with ME 49 strain Toxoplasma.

PURPOSE: These studies were undertaken to establish an animal model for use in studies of ocular toxoplasmosis. An animal model is needed to examine the development, progression, and resolution of ocular Toxoplasma infections and to study the effects on the disease of currently used and experimental therapies. METHODS: Cysts of the ME 49 strain of Toxoplasma gondii were injected intraperitoneally into each of 60 golden hamsters. The hamsters' eyes were examined before inoculation and at intervals after inoculation, and fundus photographs were taken. Histologic sections were analyzed and photographed to document the ocular effects of the infection. RESULTS: Retinochoroiditis was found in both eyes of all hamsters within 2 to 3 weeks of inoculation. The disease resolved spontaneously without treatment and was quiescent in most cases at 12 weeks after inoculation. The animals remained in good general health, and those tested had high antibody titers to Toxoplasma (1:256 to 1:32,000) at 6 months after the infection. The discovery of cysts and lesions in the retina confirmed the diagnosis. CONCLUSIONS: Although the lesions were not identical to those of human disease, this animal model of ocular toxoplasmosis offers several advantages: reproducibility, short incubation time, spontaneous resolution without treatment, consistent production of cysts, and ease of inoculation intraperitoneally without intraocular injection.

The influence of bismuth subgallate and adrenaline paste upon operating time and operative blood loss in tonsillectomy.

The aims of this study were to demonstrate the effect of bismuth subgallate and adrenaline paste application to the tonsillar fossae on operating time and peroperative blood loss during tonsillectomy. Ninety-eight patients were included in a prospective randomized trial. Bismuth subgallate powder is mixed with 10 ml of normal saline and 0.03 ml of 1:1000 adrenaline to make a paste. This paste is used as a topical haemostatic agent during tonsillectomy. Bismuth subgallate activates Factor XII and therefore accelerates the coagulation cascade. Adrenaline causes vasoconstriction and promotes platelet aggregation. The application of bismuth subgallate and adrenaline paste to the tonsillar fossae during tonsillectomy reduces operating time by 23 per cent for Consultant staff (p < 0.05) and 32 per cent for Junior staff (p < 0.05). Blood loss is reduced by 21 per cent (p > 0.05), for the average paediatric tonsillectomy.