Decreased Perifoveal Sensitivity Detected by Microperimetry in Patients Using Hydroxychloroquine and without Visual Field and Fundoscopic Anomalies

Purpose. To evaluate the usefulness of microperimetry in the early detection of the ocular anomalies associated with the use of hydroxychloroquine. Methods. Prospective comparative case series study comprising 14 healthy eyes of 7 patients (group A) and 14 eyes of 7 patients under treatment with hydroxychloroquine for the treatment of rheumatologic diseases and without fundoscopic or perimetric anomalies (group B). A comprehensive ophthalmological examination including microperimetry (MP) and spectraldomain optical coherence tomography was performed in both groups. Results. No significant differences were found in mean MP foveal sensitivity between groups (P = 0.18). However, mean MP overall sensitivity was significantly higher in group A (29.05 ± 0.57 dB versus group B, 26.05 ± 2.75 dB; P < 0.001). Significantly higher sensitivity values were obtained in group A in comparison to group B for the three eccentric loci evaluated (P < 0.001). Conclusion. Microperimetry seems to be a useful tool for the early detection of retinal damage in patients treated with hydroxychloroquine.

Propofol sedation administered by cardiologists for patients undergoing catheter ablation for ventricular tachycardia

AIMS Propofol sedation has been shown to be safe for atrial fibrillation ablation and internal cardioverter-defibrillator implantation but its use for catheter ablation (CA) of ventricular tachycardia (VT) has yet to be evaluated. Here, we tested the hypothesis that VT ablation can be performed using propofol sedation administered by trained nurses under a cardiologist's supervision. METHODS AND RESULTS Data of 205 procedures (157 patients, 1.3 procedures/patient) undergoing CA for sustained VT under propofol sedation were analysed. The primary endpoint was change of sedation and/or discontinuation of propofol sedation due to side effects and/or haemodynamic instability. Propofol cessation was necessary in 24 of 205 procedures. These procedures (Group A; n = 24, 11.7%) were compared with those with continued propofol sedation (Group B; n = 181, 88.3%). Propofol sedation was discontinued due to hypotension (n = 22; 10.7%), insufficient oxygenation (n = 1, 0.5%), or hypersalivation (n = 1, 0.5%). Procedures in Group A were significantly longer (210 [180-260] vs. 180 [125-220] min, P = 0.005), had a lower per hour propofol rate (3.0 ± 1.2 vs. 3.8 ± 1.2 mg/kg of body weight/h, P = 0.004), and higher cumulative dose of fentanyl administered (0.15 [0.13-0.25] vs. 0.1 [0.05-0.13] mg, P < 0.001), compared with patients in Group B. Five (2.4%) adverse events occurred. CONCLUSION Sedation using propofol can be safely performed for VT ablation under the supervision of cardiologists. Close haemodynamic monitoring is required, especially in elderly patients and during lengthy procedures, which carrying a higher risk for systolic blood pressure decline.

The outcome in Australian children with hyperinsulinism of infancy: early extensive surgery in severe cases lowers risk of diabetes

AIMS Hyperinsulinism of infancy (HI) is characterized by unregulated insulin secretion in the presence of hypoglycaemia, often resulting in brain damage. Pancreatic resection for control of hypoglycaemia is frequently resisted because of the risk of diabetes mellitus (DM). We investigated retrospectively 62 children with HI from nine Australian treatment centres born between 1972 and 1998, comparing endocrine and neurological outcome in 28 patients receiving medical therapy alone with 34 who required pancreatic resection to control their hypoglycaemia. METHODS History, treatment and clinical course were ascertained from file audit and interview. Risk of DM (hazard ratio) attributable to age at surgery (< vs. greater than or equal to 100 days at last pancreatectomy) and extent of resection (< vs. greater than or equal to 95%) were calculated using Cox proportional hazards regression and categorical variables compared by the chi(2) -test. Neurological outcome (normal, mild deficit or severe deficit) was derived from the most authoritative source. RESULTS Surgically treated patients had a greater birthweight, earlier presentation and higher plasma insulin levels. Of 18 infants < 100 days and 16 greater than or equal to 100 days of age at surgery, four (all greater than or equal to 100 days) became diabetic as an immediate consequence of surgery and five (two < 100 days and three greater than or equal to 100 days) became diabetic 7-18 years later. Surgery greater than or equal to 100 days and pancreatectomy greater than or equal to 95% were associated with development of diabetes (HR = 12.61, CI 1.53-104.07 and HR = 7.03, CI 1.43-34.58, respectively). Neurodevelopmental outcome was no different between the surgical and medical groups with 44% overall with neurological deficits. Patients euglycaemic within 35 days of the first symptom of hypoglycaemia (Group A) had a better neurodevelopmental outcome than those still hypoglycaemic > 35 days from first presentation (Group B) (P = 0.007). Prolonged hypoglycaemia in Group B was due either to delayed diagnosis or to need for repeat surgery because of continued hypoglycaemia. Within Group A, medically treated patients (who presented later with apparently milder disease) had a higher incidence of neurodevelopmental deficit (n = 15, four mild, three severe deficit) compared with surgically treated patients (n = 18, two mild, none severe deficit) (P < 0.025). CONCLUSIONS Poor neurodevelopmental outcome remains a major problem in hyperinsulinism of infancy. Risk of diabetes mellitus with pancreatectomy varies according to age at surgery and extent of resection. Patients presenting early with severe disease have a better neurodevelopmental outcome and lower risk of diabetes if they are treated with early extensive surgery.

Immunohistological analysis of Tannerella forsythia-induced lesions in a murine model

Tannerella forsythia has been implicated as a defined periodontal pathogen. In the present study a mouse model was used to determine the phenotype of leukocytes in the lesions induced by subcutaneous injections of either live (group A) or nonviable (group B) T. forsythia. Control mice (group C) received the vehicle only. Lesions were excised at days 1, 2, 4, and 7. An avidin-biotin immunoperoxidase method was used to stain infiltrating CD4(+) and CD8(+) T cells, CD14(+) macrophages, CD19(+) B cells, and neutrophils. Hematoxylin and eosin sections demonstrated lesions with central necrotic cores surrounded by neutrophils, macrophages and lymphocytes in both group A and group B mice. Lesions from control mice exhibited no or only occasional solitary leukocytes. In both groups A and B, neutrophils were the dominant leukocyte in the lesion 1 day after injection, the numbers decreasing over the 7-day experimental period. There was a relatively low mean percent of CD4(+) and CD8(+) T cells in the lesions and, whereas the percent of CD8(+) T cells remained constant, there was a significant increase in the percent of CD4(+) T cells at day 7. This increase was more evident in group A mice. The mean percent of CD14(+) macrophages and CD19(+) B cells remained low over the experimental period, although there was a significantly higher mean percent of CD19(+) B cells at day 1. In conclusion, the results showed that immunization of mice with live T. forsythia induced a stronger immune response than nonviable organisms. The inflammatory response presented as a nonspecific immune response with evidence of an adaptive (T-cell) response by day 7. Unlike Porphyromonas gingivalis, there was no inhibition of neutrophil migration.

Processing of English words with fine acoustic contrasts and simple tones: A mismatch negativity study

The purpose of this study was to compare the robustness of the event-related potential (ERP) response, called the mismatch negativity (MMN), when elicited by simple tone stimuli (differing in frequency, duration, or intensity) and speech stimuli (CV nonword contrast /de:/ vs. /ge:/ and CV word contrast /deI/ vs. /geI/). The study was conducted using 30 young adult subjects (Groups A and B; n = 15 each). The speech stimuli were presented to Group A at a stimulus onset asynchrony (SOA) of 610 msec and to Group B at an SOA of 900 msec. The tone stimuli were presented to both groups at an SOA of 610 msec. MMN responses were elicited by the simple tone stimuli (66.7%-96.7% of subjects with MMN "present," or significantly different from zero, p < 0.05) but not the speech stimuli (10% subjects with MMN present for nonwords, 10% for words). The length of the SOA (610 msec or 900 msec) had no effect on the ability to obtain consistent MMN responses to the speech stimuli. The results indicated a lack of robust MMN elicited by speech stimuli with fine acoustic contrasts under carefully controlled methodological conditions. The implications of these results are discussed in relation to conflicting reports in the literature of speech-elicited MMNs, and the importance of appropriate methodological design in MMN studies investigating speech processing in normal and pathological populations.

Fluid shifts have no influence on ciprofloxacin pharmacokinetics in intensive care patients with intra-abdominal sepsis

This study aimed to investigate whether fluid shifts alter ciprofloxacin pharmacokinetics in critically ill patients over time. Patients >= 18 years, with normal renal function, requiring intensive care treatment and parenteral antibiotics were enrolled. Group A (22 patients) included patients with documented intra-abdominal infections. Group B (18 patients) included patients with severe sepsis from other causes. All patients received intravenous ciprofloxacin 400 mg every 8 h infused over 60 min. Eight timed blood specimens were taken on days 0, 2 and 7. Ciprofloxacin plasma concentrations were determined using high performance liquid chromatography. There were no significant differences between the pharmacokinetics of the two groups or over time. Ciprofloxacin pharmacokinetics in critically ill patients do not change over time, and intra-abdominal sepsis does not alter ciprofloxacin pharmacokinetic parameters to a greater degree than sepsis from other causes in critically ill patients. (c) 2005 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Ototoxicity and tolerance assessment of a TrisEDTA and polyhexamethylene biguanide ear flush formulation in dogs

Clinically healthy mixed breed dogs (n = 20) were used to determine if a Tris (tromethamine)-buffered test solution, Otinide((R)) (Trademark of Dermcare-Vet Pty-Ltd, Australia), containing disodium ethylenediamine tetraacetic acid (EDTA; 1.21 g/L) and polyhexamethylene biguanide (PHMB; 0.22 g/L) caused ototoxicity or vestibular dysfunction. The dogs were randomly assigned to either a control group (group A, n = 10) receiving saline, or a treatment group (group B, n = 10) receiving the test solution. Phase 1 of the study consisted of applying 5.0 mL of saline to both ears of the control group (group A) and 5 mL of test solution to both ears of the test group (group B), for 21 days. A bilateral myringotomy was then performed on each dog under deep sedation. Phase 2 of the study then consisted of applying 2.0 mL of the saline to both ears of the control group (group A) and 2.0 mL of the test solution to both ears of the test group (group B), for 14 days. Throughout the study, dogs were examined for clinical health, and underwent otoscopic, vestibular and auditory examinations. The auditory examinations included brainstem auditory evoked potential (BAEP) threshold and supra-threshold assessments using both click and 8 kHz tone burst stimuli. The absence of vestibular signs and effects on the BAEP attributable to the test solution suggested the test solution could be applied safely to dogs, including those with a damaged tympanic membrane.

K-Ar and 40Ar/39Ar ages of dikes emplaced in the onshore basement of the Santos Basin, Resende area, SE Brazil: implications for the South Atlantic opening and tertiary reactivation

New K-Ar and Ar-40/Ar-39 data of tholeiitic and alkaline dike swarms from the onshore basement of the Santos Basin (SE Brazil) reveal Mesozoic and Tertiary magmatic pulses. The tholeiitic rocks (basalt, dolerite, and microgabbro) display high TiO2 contents (average 3.65 wt%) and comprise two magmatic groups. The NW-oriented samples of Group A have (La/Yb)N ratios between 15 and 32.3 and range in age from 192.9 +/- 2.2 to 160.9 +/- 1.9 Ma. The NNW-NNE Group B samples, with (La/Yb)(N) ratios between 7 and 16, range from 148.3 +/- 3 to 133.9 +/- 0.5 Ma. The alkaline rocks (syenite, trachyte, phonolite, alkaline basalts, and lamprophyre) display intermediate-K contents and comprise dikes, plugs, and stocks. Ages of approximately 82 Ma were obtained for the lamprophyre dikes, 70 Ma for the syenite plutons, and 64-59 Ma for felsic dikes. Because Jurassic-Early Cretaceous basic dikes have not been reported in SE Brazil, we might speculate that, during the emplacement of Group A dikes, extensional stresses were active in the region before the opening of the south Atlantic Ocean and coeval with the Karoo magmatism described in South Africa. Group B dikes yield ages compatible with those obtained for Serra Geral and Ponta Grossa magmatism in the Parana Basin and are directly related to the breakup of western Gondwana. Alkaline magmatism is associated with several tectonic episodes that postdate the opening of the Atlantic Ocean and related to the upwelling of the Trindade plume and the generation of Tertiary basins southeast of Brazil. In the studied region, alkaline magmatism can be subdivided in two episodes: the first one represented by lamprophyre dykes of approximately 82 Ma and the second comprised of felsic alkaline stocks of approximately 70 Ma and associated dikes ranging from 64 to 59 Ma. (c) 2005 Elsevier Ltd. All rights reserved.

Fracture load and marginal fit of shrinkage-free ZrSiO4 all-ceramic crowns after chewing simulation

The aim of this in vitro study was to evaluate the fracture load and marginal accuracy of crowns made from a shrinkage-free ZrSiO4 ceramic cemented with glass-ionomer or composite cement after chewing simulation. Thirty-two human mandibular molars were randomly divided into two groups. All teeth were prepared for and restored with shrinkage-free ZrSiO4 ceramic crowns (Everest HPC (R), KaVo). The crowns of group A (N = 16) were luted to the teeth using KetacCem (R) and group B (N = 16) were adhesively cemented using Panavia (R) 21EX. Measurements of the marginal accuracy before and after cementation were made using replicas and an image analysis system. All specimens were exposed to 1.2 million cycles of thermo-mechanical fatigue in a chewing simulator. Surviving specimens were subsequently loaded until fracture in a static testing device. Fracture loads (N) were recorded. All specimens survived chewing simulation. The mean fracture loads (+/- s.d.) were Group A, 1622 N (+/- 433); group B, 1957 N (+/- 806). There was no significant difference between the two groups (P > 0.05). The marginal gap values before cementation were (mean +/- s.d.): Group A, 32.7 mu m (+/- 6.8); group B, 33.0 mu m (+/- 6.7).The mean marginal gap values after cementation were (+/- s.d.): Group A, 44.6 mu m (+/- 6.7); group B, 46.6 mu m (+/- 7.7). The marginal openings were significantly higher after cementation for both groups (P < 0.05). All test groups demonstrated fracture load and marginal accuracy values within the range of clinical acceptability.

Method for the synthesis of highly pure vaccines using the lipid core peptide system

Traditional vaccines consisting of whole attenuated microorganisms, killed microorganisms, or microbial components, administered with an adjuvant (e.g. alum), have been proved to be extremely successful. However, to develop new vaccines, or to improve upon current vaccines, new vaccine development techniques are required. Peptide vaccines offer the capacity to administer only the minimal microbial components necessary to elicit appropriate immune responses, minimizing the risk of vaccination associated adverse effects, and focusing the immune response toward important antigens. Peptide vaccines, however, are generally poorly immunogenic, necessitating administration with powerful, and potentially toxic adjuvants. The attachment of lipids to peptide antigens has been demonstrated as a potentially safe method for adjuvanting peptide epitopes. The lipid core peptide (LCP) system, which incorporates a lipidic adjuvant, carrier, and peptide epitopes into a single molecular entity, has been demonstrated to boost immunogenicity of attached peptide epitopes without the need for additional adjuvants. The synthesis of LCP systems normally yields a product that cannot be purified to homogeneity. The current study describes the development of methods for the synthesis of highly pure LCP analogs using native chemical ligation. Because of the highly lipophilic nature of the LCP lipid adjuvant, difficulties (e.g. poor solubility) were experienced with the ligation reactions. The addition of organic solvents to the ligation buffer solubilized lipidic species, but did not result in successful ligation reactions. In comparison, the addition of approximately 1% (w/v) sodium dodecyl sulfate (SDS) proved successful, enabling the synthesis of two highly pure, tri-epitopic Streptococcus pyogenes LCP analogs. Subcutaneous immunization of B10.BR (H-2(k)) mice with one of these vaccines, without the addition of any adjuvant, elicited high levels of systemic IgG antibodies against each of the incorporated peptides. Copyright (c) 2006 European Peptide Society and John Wiley & Sons, Ltd.

Conservation and accessibility of an inner core lipopolysaccharide epitope of Neisseria meningitidis

We investigated the conservation and antibody accessibility of inner core epitopes of Neisseria meningitidis lipopolysaccharide (LPS) because of their potential as vaccine candidates. An immunoglobulin G3 murine monoclonal antibody (MAb), designated MAb B5, was obtained by immunizing mice with a galE mutant of N. meningitidis H44/76 (B.15.P1.7,16 immunotype L3). We have shown that MAb B5 can bind to the core LPS of wild-type encapsulated MC58 (B.15.P1.7,16 immunotype L3) organisms in vitro and ex vivo. An inner core structure recognized by MAb B5 is conserved and accessible in 26 of 34 (76%) of group B and 78 of 112 (70%) of groups A, C, W, X, Y, and Z strains. N. meningitidis strains which possess this epitope are immunotypes in which phosphoethanolamine (PEtn) is linked to the 3-position of the beta-chain heptose (HepII) of the inner core. In contrast, N. neningitidis strains lacking reactivity with MAb B5 have an alternative core structure in which PEtn is linked to an exocyclic position (i.e., position 6 or 7) of HepII (immunotypes L2, L4, and L6) or is absent (immunotype L5). We conclude that MAb B5 defines one or more of the major inner core glycoforms of N. meningitidis LPS. These findings support the possibility that immunogens capable of eliciting functional antibodies specific to inner core structures could be the basis of a vaccine against invasive infections caused by N. meningitidis.

AVALIAÇÃO DAS TÁBUAS ÓSSEAS VESTIBULARES E LINGUAIS DOS DENTES ANTERIORES INFERIORES E MOLARES SUPERIORES APÓS O TRATAMENTO COM OS APARELHOS FUNCIONAIS FIXOS FORSUS E TWIN FORCE BITE CORRECTOR

Pelo fato das consequências do uso de aparelhos ortopédicos fixos sobre o periodonto ósseo vestibular e lingual ainda serem uma incógnita para o ortodontista clínico e pesquisador, este estudo teve como objetivo avaliar, por meio de tomografia computadorizada de feixe cônico (TCFC) as alterações em espessura das tábuas ósseas vestibulares e linguais em primeiros molares superiores e incisivos e caninos inferiores, após a utilização de aparelhagem fixa e dos aparelhos Twin Force (grupo A) e Forsus (grupo B) para o tratamento da maloclusão de Classe II, 1ª divisão. Para tanto, obteve-se uma amostra de 22 pacientes jovens adultos, divididos em dois grupos, de acordo com o aparelho propulsor da mandíbula. Grupo experimental A: 11 pacientes, 6 masculinos e 5 femininos, com idade média de 15,09 anos na instalação do Twin Force, e 11 pacientes, 7 masculinos e 4 femininos, com idade média de 15,45 anos na instalação do Forsus. O tempo médio de uso do aparelho Twin Force foi de 3,73 meses e do Forsus, 7,09 meses. O grupo A realizou TCFC antes do início do tratamento (T1), antes da instalação do Twin Force (T2), após a remoção do Twin Force (T3); e o grupo B somente antes da instalação do Forsus (T2) e após a remoção do Forsus (T3). Para comparação entre os tempos T2 e T3 foi utilizado o teste t pareado e entre os tempos T1, T2 e T3 foi utilizada a Análise de Variância (ANOVA) a um critério e o teste post-hoc de Tukey. Para comparação entre os grupos foi utilizado o teste t . Na comparação intergrupos os resultados evidenciaram que não houve diferença estatisticamente significante entre as alterações das espessuras das tábuas ósseas vestibular e lingual; por outro lado, na avaliação intra-grupo, de 48 medidas avaliadas, no grupo A houve reduções estatisticamente significantes nos terços cervical e médio por vestibular, nos dentes anteroinferiores e nos primeiros molares superiores e aumento nos terços cervical e médio, por lingual nos dentes anteriores inferiores, totalizando 25 medidas significantes. Já no grupo B, houve aumento significante da tábua óssea lingual nos dentes anteriores inferiores e redução em vestibular nos molares superiores, totalizando apenas sete medidas significantes, mas com mais medidas significantes de redução óssea vestibular em terços cervical e médio nos primeiros molares superiores, em comparação com o grupo A. Não houve diferença significante entre as medições obtidas com voxel 0,2 mm e 0,4 mm e nem dimorfismo entre os gêneros. As reduções em espessura óssea alveolar, principalmente em terços cervicais e médios vestibulares nos dentes avaliados neste estudo são um alerta ao clínico, para que realize essa abordagem diagnóstica periodontal antes de iniciar o tratamento ortodôntico.

Dimensional changes in the ageing cornea

The study investigated the central and peripheral corneal characteristics of groups of subjects from 20 to 90 years of age to assist the understanding of ageing changes in the cornea, and to see whether relationships between ocular parameters were revealed. After age 45 the corneal horizontal radius of curvature gradually decreased with age. This trend was shown by the Aston University subjects (group B). The effect was very significant for the hospital patients undergoing biometry before cataract extraction operation (group D). Vertical radius of curvature showed a slight decrease with age after age 45, but similar to corneal eccentricity, this showed no significant age effect. Corneal astigmatism progressed from with the rule towards against the rule, particularly after age 60. The shift seemed mainly due to the decreasing horizontal corneal curvature. In biometry no significant age relation was found for axial length, but a significant relation was found between curvature and axial length in the larger group D. Lens thickness showed a very significant relation to age and to axial length, but no significant relation to corneal curvature. Anterior chamber depth showed a very significant relation to age, lens thickness and axial length, but no significant relation to corneal curvature. A significant age effect was found for corneal thickness decreasing with age for the central, nasal and temporal regions of the right eye. Analysis of the biometry results indicated the influence of two major factors. Firstly, the natural growth of the eye in youth, leading to greater values of axial length, radius of corneal curvature, lens thickness and anterior chamber depth. Secondly, the typical ageing changes where the increasing lens thickness caused a reduction in anterior chamber depth. The decrease in corneal thickness with age shown in some corneal regions may be a sign of ageing changes in the tissue proteins and hydration balance.

German-Irish corporate relationships:the cultural dimension

The thesis raises the question of whether or not in an age of internationalisation and globalisation, the cultural differences which exist between Germany and Ireland are still relevant to German-Irish corporate relationships or have internationally accepted best practices removed culture from the equation? The first three chapters establish the theoretical framework of the thesis by outlining the broadly culturalist/institutionalist approach, based on the work of Hofstede and Maurice et al, to be pursued, profiling the business cultures of both countries by analysing the components of their respective national institutional frameworks, and the examining existing approaches to the study of mother company-foreign subsidiary relationships. Chapters four to seven constitute the empirical section of the thesis. Using the interviews carried out with two sample groups (Sample Group A: 15 German mother companies and 14 of their Irish operations and Sample Group B: 7 Irish mother companies and 9 of their German operations), the mother companies in both groups are examined to see whether or not they demonstrate characteristics which are in keeping with their national business cultures. Their foreign operations are then analysed as is the mother company-foreign subsidiary relationship to determine whether or not any mother company influences are visible. The general approaches adopted by the two groups of mother companies to their foreign operations are compared and contrasted. Finally, differences in national attitudes and values are identified and their impact assessed. The analysis reveals that despite existing pressures towards convergence, the cultural differences between both countries are still relevant to the relationship particularly at the level of attitudes and values and although similarities in the mother company approaches to their subsidiaries are present, national specificities may nevertheless be detected.