Cardiac 123 I-MIBG Parameters at 4 Hours Derived from Earlier Acquisitions Times

Abstract Background: The clinical implementation of cardiac 123 Iodine-meta-iodobenzylguanidine ( 123 I-MIBG) scintigra

Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration

Purpose: To evaluate the safety and efficacy of repeat injections of Brimonidine Drug Delivery System (Brimo DDS) Generation 2 (Gen 2) containing 400-μg brimonidine in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Design: A phase IIb, randomized, multicenter, double-masked, sham-controlled, 30-month study (BEACON). Participants: Patients diagnosed with GA secondary to AMD and multifocal lesions with total area of > 1.25 mm2 and ≤ 18 mm2 in the study eye. Methods: Enrolled patients were randomized to treatment with intravitreal injections of 400-μg Brimo DDS (n = 154) or sham procedure (n = 156) in the study eye every 3 months from day 1 to month 21. Main Outcome Measures: The primary efficacy endpoint was GA lesion area change from baseline in the study eye, assessed with fundus autofluorescence imaging, at month 24. Results: The study was terminated early, at the time of the planned interim analysis, because of a slow GA progression rate (∼ 1.6 mm2/year) in the enrolled population. Least squares mean (standard error) GA area change from baseline at month 24 (primary endpoint) was 3.24 (0.13) mm2 with Brimo DDS (n = 84) versus 3.48 (0.13) mm2 with sham (n = 91), a reduction of 0.25 mm2 (7%) with Brimo DDS compared with sham (P = 0.150). At month 30, GA area change from baseline was 4.09 (0.15) mm2 with Brimo DDS (n = 49) versus 4.52 (0.15) mm2 with sham (n = 46), a reduction of 0.43 mm2 (10%) with Brimo DDS compared with sham (P = 0.033). Exploratory analysis showed numerically smaller loss over time in retinal sensitivity assessed with scotopic microperimetry with Brimo DDS than with sham (P = 0.053 at month 24). Treatment-related adverse events were usually related to the injection procedure. No implant accumulation was observed. Conclusions: Multiple intravitreal administrations of Brimo DDS (Gen 2) were well tolerated. The primary efficacy endpoint at 24 months was not met, but there was a numeric trend for reduction in GA progression at 24 months compared with sham treatment. The study was terminated early because of the lower-than-expected GA progression rate in the sham/control group. Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references

Bulgakov's Novel the Heart of a Dog and Yaghoobi's play: a Comparative Study on the Structural Adaptation Process

Abstrac

Histopothology of Rejected Orthotopic Corneal Grafts in the Rat

We have used an orthotopic graft model in the rat to study the histologic characteristics of corneal allograft rejection. Unrejected allogeneic grafts could not be distinguished from clear syngeneic grafts. Although donor Langerhans cells are necessary for the development of delayed-type hypersensitivity (DTH), the histopathological characteristics of rejecting corneal allografts in immunologically naive hosts were identical regardless of the presence or absence of donor Langerhans cells. By contrast, preimmunization had a dramatic effect on the histology of graft rejection. Untreated allografts placed onto pre-immunized recipients underwent a marked cellular necrosis accompanied by minimal inflammation that easily distinguished these grafts from the previous groups. These results suggest that neither the presence nor absence of DTH responsiveness correlates with the histopathological events that accompany corneal graft rejection. However, preimmunization leads to a different histologic pattern of rejection that is characterized by an intense cellular necrosis. Invest Ophthalmol Vis Sci 30: [413][414][415][416][417][418][419][420][421][422][423][424]1989 Immunologic rejection remains the leading cause of graft failure in human corneal transplants. 1 Several different species of animals have been employed to study this problem. Rabbits were used by Maumenee 2 and also by Khodadoust and Silverstein 3 ' 4 in the earliest studies of immune rejection. These studies provided valuable information on the characteristics of rejection of a true orthotopic graft. The drawback of using the rabbit was the lack of understanding of that animal's immune system. Streilein et al 5 devised a new method of studying this problem by grafting cornea heterotopically on a vascularized dermal bed in mice. This model has been used extensively by our lab ite immunological analysis of corneal allografts. However, heterotopic corneal allograft models share a common disadvantage of being unable to evaluate the role of the avascular corneal graft bed. Coster and Williams 14 developed a rat model of corneal transplantation that eliminates these obstacles and combines the attributes of both the rabbit and mouse models. We have used this model to study the characteristics of rejection of true orthotopic transplants Materials and Methods Rats Female Lewis (LEW) and Wistar-Furth (WF) inbred rats were obtained from Harlan SpragueDawley (Indianapolis, IN). These two strains differ at the entire major histocompatibility complex (MHC) 413 Downloaded from iovs.arvojournals.org on 06/28/201

Risk factors associated with xerostomia in haemodialysis patients

Abstract Background: To determine the prevalence of xerostomia and hyposalivation in Haemodialysis (HD) patients, to clarify risk factors, assess patient´s quality of life, and to establish a possible correlation among interdialytic weight gain (IDWG) and xerostomia. Material and Methods: This study was performed on a group of 50 HD patients. Data were collected using a questionnaire containing demographic and clinical variables, a visual analogue scale (VAS) for xerostomia, IDWG, and an oral health impact profile questionnaire . Unstimulated whole saliva (UWS) and stimulated whole saliva (SWS) were collected. Results: A total of 28 HD patients (56%) suffered xerostomia. Dry mouth was associated with hypertension (OR, 5.24; 95% CI, 1.11-24.89) and benzodiazepine consumption (OR, 5.96; 95% CI, 1.05-33.99). The mean xerostomia VAS and OHIP-14 scores were 31.74±14.88 and 24.38±11.98, respectively. No significant correlation was observed between IDWG% and VAS and OHIP total score. Nonetheless, a positive correlation between VAS level of thirst and IDWG% was found (r=0.48 p=0.0001). UWS and SWS means (determined in 30 patients) were 0.16±0.17 and 1.12±0.64, respectively. Decreased values of UWS and SWS were reported in 53.33% and 36.66% of HD patients. Conclusions: Xerostomia in HD has a multifactorial aetiology due to accumulative risks as advanced age, systemic disorders, drugs, fluid intake restriction, and salivary parenchymal fibrosis and atrophy. Therefore, it i

Doppler and maternal serum screening in the prediction of pregnancy complications* Doppler e marcadores séricos maternos na predição de complicações da gestação

OBJECTIVE: To compare the effectiveness of uterine artery Doppler and maternal serum screening in the prediction of pregnancy complications. MATERIALS AND METHODS: Prospective study with 49 primigravidae at their 18th gestational week, when a blood sample was collected for serum dosage by chemiluminescence (alpha-fetoprotein, human chorionic gonadotropin and nitric oxide) and radioimmunoassay (atrial natriuretic peptide). Uterine artery Doppler was performed between the 24th and 26th gestational weeks, for determining the presence or absence of notch in the flow velocity waveform. OBJETIVO: Comparar a eficácia do Doppler das artérias uterinas e de marcadores séricos maternos na predição de complicações da gestação. MATERIAIS E MÉTODOS: Trata-se de um estudo prospectivo com 49 primigestas, incluídas no estudo na 18ª semana, sendo coletada a amostra sanguínea para a realização das dosagens séricas, realizadas pelo método de quimioluminescência (alfa-fetoproteína, gonadotrofina coriô-nica humana e óxido nítrico) e radioimunoensaio (peptídio atrial natriurético). O Doppler das artérias uterinas foi realizado entre 24-26 semanas, determinando a presença ou ausência de incisura na onda de velocidade de fluxo. Na análise estatística utilizou-se o teste de Mann-Whitney, para amostras não-paramétricas, e o teste exato de Fisher, para parâmetros qualitativos. RESULTADOS: Os valores de sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo foram, respectivamente, de 8,3%, 97,0%, 50,0% e 74,4% para a alfa-fetoproteína; 8,3%, 87,9%, 20,0% e 72,5% para a gonadotrofina coriônica humana; 16,7%, 97,0%, 33,3% e 76,2% para o peptídio atrial natriurético; e 16,7%, 93,9%, 50,0% e 75,6% para o óxido nítrico. A sensibilidade do Doppler foi de 75,0%, especificidade de 63,6%, valor preditivo positivo de 57,1% e valor preditivo negativo de 87,5%. CONCLUSÃO: O Doppler das artérias uterinas é melhor preditor de complicações da gestação quando comparado a alguns marcadores séricos em populações de baixo risco. 5. PhD, Professor, Department of Gynecology and Obstetrics several gestational disorders, especially preeclampsia. Some of these tests are simple, other, invasive; some of them have been extensively evaluated, others still remain under clinical investigation. The literature review demonstrates a high level of disagreement as far as the sensitivity and predictive value of several of these tests are concerned, and an ideal test for screening the main gestational and perinatal pathologies is still to be found (1) . The greatest majority of current studies about markers for gestational and perinaCosta FS, Rocha RS, Cunha SP, Reis FC, Berezowski AT, Antunes-Rodrigues J. Doppler e marcadores séricos maternos na predição de complicações da gestação. Radiol Bras. 2008;41(1):7-12

Enhanced interpretation of newborn screening results without analyte cutoff values

A collaboration among 157 newborn screening programs in 47 countries has lead to the creation of a database of 705,333 discrete analyte concentrations from 11,462 cases affected with 57 metabolic disorders, and from 631 heterozygotes for 12 conditions. This evidence was first applied to establish disease ranges for amino acids and acylcarnitines, and clinically validate 114 cutoff target ranges. Objective: To improve quality and performance with an evidence-based approach, multivariate pattern recognition software has been developed to aid in the interpretation of complex analyte profiles. The software generates tools that convert multiple clinically significant results into a single numerical score based on overlap between normal and disease ranges, penetration within the disease range, differences between specific conditions, and weighted correction factors. Design: Eighty-five on-line tools target either a single condition or the differential diagnosis between two or more conditions. Scores are expressed as a numerical value and as the percentile rank among all cases with the condition chosen as primary target, and are compared to interpretation guidelines. Tools are updated automatically after any new data submission (2009- 2011: 5.2 new cases added per day on average). Main outcome measures: Retrospective evaluation of past cases suggest that these tools could have avoided at least half of 277 false positive outcomes caused by carrier status for fatty acid oxidation disorders, and could have prevented 88% of false negative events caused by cutoff 7 values set inappropriately. In Minnesota, their prospective application has been a major contributing factor to the sustained achievement of a false positive rate below 0.1% and a positive predictive value above 60%. Conclusions: Application of this computational approach to raw data could make cutoff values for single analytes effectively obsolete. This paradigm is not limited to newborn screening and is applicable to the interpretation of diverse multi-analyte profiles utilized in laboratory medicine. Abstract wor