Reproducibility of semi-quantitative assessment of aortic valve calcification and valve motion on echocardiography: a small-scale study.

BACKGROUND: Aortic stenosis (AS) is the most common degenerative valve disease in high income countries. While hemodynamic metrics are commonly used to assess severity of stenosis, they are impacted by loading conditions and stroke volume and are often discordant. Anatomic valve assessments such as aortic valve calcification (AVC) and valve motion (VM) during transthoracic echocardiography (TTE) can offer clues to disease severity. The reliability of these semi-quantitatively assessed anatomic imaging parameters is unknown. METHODS: This is a retrospective study of semi-quantitative assessment of AVC and valve VM on TTE. TTEs representing a range of AS severities were identified. The degree of calcification of the aortic valve and the degree of restricted VM were assessed in standard fashion. AVC scores and valve motion were assessed by readers with varied training levels blinded to the severity of AS. Correlation and inter-reader reliability between readers were assessed. RESULTS: 420 assessments (210 each for AVC and VM) were collected for 35 TTEs. Correlation of AVC for imaging trainees (fellows and students, respectively), ranged from 0.49 (95% CI 0.18-0.70) to 0.62 (95% CI 0.36-0.79) and 0.58 (95% CI 0.30-0.76) to 0.54 (95% CI 0.25-0.74) for VM. Correlation of anatomic assessments between echocardiographer-assigned AVC grades was r = 0.76 (95% CI 0.57-0.87)). The correlation between echocardiographer-assigned assessment of VM was r = 0.73 (95% CI 0.53-0.86), p < 0.00001 for both. For echocardiographer AVC assessment, weighted kappa was 0.52 (0.32-0.72), valve motion weighted kappa was 0.60 (0.42-0.78). CONCLUSION: There was good inter-reader correlation between TTE-based semi-quantitative assessment of AVC and VM when assessed by board certified echocardiographers. There was modest inter-reader reliability of semi-quantitative assessments of AVC and VM between board certified echocardiographers. Inter-reader correlation and reliability between imaging trainees was lower. More reliable methods to assess TTE based anatomic assessments are needed in order to accurately track disease progression. CLINICAL TRIAL NUMBER: STUDY00003100.

Validación de la prueba nacional de pesquisa de trastornos de desarrollo psicomotor en niños menores de 6 años / Validation for screening test of detecting psychomotor development problems in children under six

Introducción. El uso de una prueba de pesquisa en los primeros años de vida permite la detección temprana de retrasos en el desarrollo psicomotor y su tratamiento oportuno. En la Argentina contamos con una Prueba Nacional de Pesquisa preparada en base a un estudio nacional. El objetivo del trabajo fue validar la prueba, comparando sus resultados con evaluaciones diagnósticas, realizadas en forma simultánea por varios servicios del Hospital Garrahan. Pacientes y métodos. Se seleccionó una muestra de 106 niños de 0 a 5,99 años que concurrían al área de bajo riesgo del Hospital. Se realizaron los siguientes estudios diagnósticos: evaluación del desarrollo psicomotor (Bayley II), examen neurológico, salud mental, coeficiente intelectual (Wechsler, Terman), conducta adaptativa (Vineland), lenguaje (prueba de Gardner receptiva y expresiva, ITPA), audición (emisiones otoacústicas, audiometría tonal, PEAT), examen visual. Se utilizó el DSM-IV como referencia de trastornos del desarrollo. Se evaluó la sensibilidad y especificidad obtenidas según la aplicación de diferentes puntos de corte (número de ítems fracasados). Resultados. El mejor punto de corte se estableció en un ítem tipo A o 2 tipo B, con una sensibilidad del 80%, especificidad: 93%, valor predictivo positivo: 94%, valor predictivo negativo: 77%, porcentaje de coincidencia: 85%. Fue inesperada la elevada prevalencia de problemas de desarrollo encontrada en la muestra: 57%. La prueba es capaz de detectar problemas en las cuatro áreas del desarrollo, incluidos trastornos del lenguaje. Conclusión. Los resultados confirman a la Prueba Nacional de Pesquisa como un instrumento válido para ser usado en el primer nivel de atención para el reconocimiento de niños con sospecha de sufrir trastornos del desarrollo. Asimismo, el trabajo de información permite establecer diferentes puntos de corte y constituye un instrumento útil para su aplicación en la práctica pediátrica.

The use of a screening test in the first years of life allows the early detection of delays of psychomotor development and its treatment, thus contributing to improve the prognosis of the child with special needs. In Argentina, a screening test for detecting developmental problems in children under 6, made with local children and data is available (PRUNAPE). A validation procedure for this test was carried out on 106 children attending at low risk outpatient clinic in Hospital Garrahan. The test was administered to the children together with a battery of diagnostic examinations and studies, performed by experienced specialists from different Hospital services: psychomotor development, neurology examination, mental health, intellectual quotient (Wechsler, Terman), adaptive behaviour (Vineland), language (Gardner expressive and receptive, ITPA), hearing (otoacustic emissions, audiometry, BERA), vision. The DSM ­IV was used as a reference for developmental problems. Using as a failure criterion to the PRUNAPE, the failure of performing correctly one type A item or two type B item, sensitivity of the test was 80%, specificity, 93%; positive predictive value, 95%; negative predictive value, 77%; overall agreement, 85%. A very high prevalence of developmental problems was found: 57%. PRUNAPE was found to be capable of detecting a wide range of problems. These results confirm PRUNAPE as a valuable instrument for early detection of developmental problems in paediatric practice at the primary care level.

Inheritance of trunk banding in the tetra (Gymnocorymbus ternetzi Characidae).

The tetra (Gymnocorymbus ternetzi) exhibits two phenotypes associated with trunk banding. Fish possess either a smoky-gray coloration with two prominent black vertical bands located directly behind the operculum (black tetra) or a lighter coloration and lack these bands (white skirt tetra). Segregation patterns observed from the progenies of 11 different crosses suggest that the inheritance of these phenotypes is controlled by two autosomal loci acting in a complementary fashion, with dominance at both loci required for the expression of the darker, banded phenotype.

Caudal spotting in the beacon fish (Hemigrammus ocellifer Characidae).

The beacon fish (Hemigrammus ocellifer) exhibits two phenotypes associated with spotting at the base of the caudal fin, with fish either possessing (H. o. ocellifer) or lacking (H. o. falsus) a prominent red spot in this region. Segregation patterns observed from the progenies of 15 different crosses support a hypothesis that caudal spotting in this species is controlled by a single gene with two alleles, for which the caudal spotting allele is completely dominant.

A witness breaks his silence: the meaning of a therapist's response to an adolescent's self-destruction.

I describe the case of a self-mutilating adolescent girl and my dilemma, as her therapist, about telling her parents about her self-abuse. I use two complementary, mutually enhancing relational theories of trauma--Ferenczi's (1933) and Davies and Frawley's (1994)--to help understand the minefield I was in. Davies and Frawley describe certain relational configurations that are typical of trauma victims. I believe that it is not only unavoidable but therapeutically vital for therapists to participate in these configurations so they can know the patient's experience in a personal way. It is also crucial that they be witnesses who provide recognition for the patient's pain and, in so doing, relieve the intolerable feeling of isolation that Ferenczi proposed was the most basic trauma. In addition, I discuss the observation that some people who have not been previously traumatized in any gross way manifest characteristics of trauma.

An evaluation of Hsp90 as a mediator of cortical patterning in Tetrahymena.

This study asks two questions: 1) whether Hsp90 is involved in the regulation of cortical patterning in Tetrahymena, and 2) if it is, whether specific defects in this regulation can be attributed to functional insufficiency of the Hsp90 molecule. To address question 1, we compared the effects of a specific inhibitor of Hsp90, geldanamycin, on population growth and on development of the oral apparatus in two Tetrahymena species, T. pyriformis and T. thermophila. We observed that geldanamycin inhibits population growth in both species at very low concentrations, and that it has far more severe effects on oral patterning in T. pyriformis than in T. thermophila. These effects are parallel to those of high temperature in the same two species, and provide a tentative affirmative answer to the first question. To address question 2, we ascertained the base sequence of the genes that encode the Hsp90 molecules which are induced at high temperatures in both Tetrahymena species, as well as corresponding sequences in Paramecium tetraurelia. Extensive comparative analyses of the deduced amino acid sequences of the Hsp90 molecules of the two Tetrahymena species indicate that on the basis of what we currently know about Hsp90 both proteins are equally likely to be functional. Phylogenetic analyses of Hsp90 amino acid sequences indicate that the two Tetrahymena Hsp90 molecules have undergone a similar number of amino acid substitutions from their most recent common ancestor, with none of these corresponding to any known functionally critical region of the molecule. Thus there is no evidence that the Hsp90 molecule of T. pyriformis is functionally impaired; the flaw in the control of cortical patterning is more likely to be caused by defects in mechanism(s) that mediate the response to Hsp90, as would be expected from the "Hsp90 capacitor" model of Rutherford and Lindquist.

The effects of supraoptimal temperatures on population growth and cortical patterning in Tetrahymena pyriformis and Tetrahymena thermophila: a comparison.

In this investigation, we compare the multiplication rates and morphogenetic responses of the two most studied Tetrahymena species, T. pyriformis and T. thermophila, at supraoptimal temperatures. Although the upper temperature limits differ greatly in the two species, the pattern of growth responses to high temperature is for the most part similar, with some differences in detail. The transient recovery of cell division at the highest temperature that allows cell division, characteristic of T. pyriformis, is observed in a less distinct form in T. thermophila. Moreover, there is a remarkable difference in developmental response, with drastic abnormalities in patterning of oral structures during the transient recovery of cell division in T. pyriformis, and far more limited abnormalities under similar conditions in T. thermophila. The abnormalities result from spatial disorder in the alignment and orientation of basal body pairs within the early oral primordium, followed by failures in the realignment that normally occurs as oral structures (membranelles and undulating membrane) mature. Both the initial spatial disorder and the failures in realignment are far more severe in T. pyriformis than in T. thermophila.

Nuclear and cortical regulation in doublets of Paramecium: II. When and how do two cortical domains reorganize to one?

Homopolar doublets with twofold rotational symmetry were generated in Paramecium tetraurelia and in P. undecaurelia by electrofusion or by arrested conjugation. These doublets underwent a complex cortical reorganization over time, which led to their reversion to singlets. This reorganization involved a reduction in number of ciliary rows, a progressive inactivation and loss of one oral meridian, and a reduction and eventual disappearance of one cortical surface (semicell) situated between the two oral meridians. The intermediate steps of this reorganization included some processes that resemble those previously described in regulating doublets of other ciliates, and others that are peculiar to members of the "P. aurelia" species-group and some of its close relatives. The former included a disappearance of one cortical landmark (a contractile vacuole meridian) and transient appearance of another (a third cytoproct) within the narrower semicell. The latter included a reorganization of the paratene zone and the associated invariant (non-duplicating) region to occupy the entire narrower semicell and a redistribution of zones of most active basal-body proliferation within the opposite, wider semicell. The final steps of reorganization involved anterior displacement, invagination, and resorption of one of the two oral apparatuses and eventual disappearance of the associated oral meridian. An oral meridian deprived of its oral apparatus, either by spontaneous resorption or microsurgical removal, could persist for some time in "incomplete doublets" before regulating to the singlet condition. The phylogenetically widespread events encountered in the regulation of doublets to singlets suggest that Paramecium shares some of the global regulatory properties that are likely to be ancestral in ciliates. The more specific events are probably associated with the complex cytoskeletal architecture of this organism and with the frequent occurrence of autogamy that was described in the preceding study (Prajer et al. 1999).

Anti-Yo antibody-positive cerebellar degeneration associated with endometrial carcinoma: case report and review of the literature.

Paraneoplastic cerebellar degeneration (PCD) is a rare, severely debilitating disease, often with a rapid onset and progression, which predate the diagnosis of malignancy. Despite characteristic features, diagnosis is commonly difficult and successful therapy, which relies on early instigation of treatment, is rare. Here we present a patient in whom anti-Yo antibody-positive PCD was associated with endometrial carcinoma and an extensive review of the literature outlining the clinical features, pathogenesis and treatment of PCD.

Monogenic control of iris coloration in the January tetra (Hemigrammus hyanuary Characidae).

The January tetra (Hemigrammus hyanuary Durbin) exhibits two eye color phenotypes. These have a silver iris, which is characteristic of the species, and a green color variant. Segregation patterns observed in the progenies from 12 different crosses support an hypothesis for the monogenic inheritance of iris coloration in this species.

The effect of oral and intravenous methylprednisolone treatment on subsequent relapse rate in multiple sclerosis.

We investigated the effect of oral and intravenous methylprednisolone treatment on subsequent relapse rate in patients with multiple sclerosis. Following a double blind trial designed to compare the effect of oral and intravenous methylprednisolone treatment on promoting recovery from acute relapses of multiple sclerosis, 80 patients were followed for two years with six-monthly assessments during which all subsequent relapses were recorded. The annual relapse rate was slightly higher in the oral compared with the intravenous methylprednisolone-treated patients (1.06 vs. 0.78), but the adjusted difference between the two groups was not statistically significant (0.18; 95% CI -0.19 to 0.55, P=0.3). The time to onset and the severity of the first relapse after treatment, the number of relapse free patients at the end of the follow-up period, and the severity of the relapses during the follow-up period were similar in the two groups. This trial did not show a statistically significant difference in relapse rate during the first two years following oral compared with intravenous methylprednisolone treatment.