Risk scores' performance and their impact on operative decision-making in left-sided endocarditis: a cohort study.

The accuracy of contemporary risk scores in predicting perioperative mortality in infective endocarditis (IE) remains controversial. The aim is to evaluate the performance of existent mortality risk scores for cardiovascular surgery in IE and the impact on operability at high-risk thresholds. A single-center retrospective review of adult patients diagnosed with acute left-sided IE undergoing surgery from May 2014 to August 2019 (n = 142) was done. Individualized risk calculation was obtained according to the available mortality risk scores: EuroScore I and II, PALSUSE, Risk-E, Costa, De Feo-Cotrufo, AEPEI, STS-risk, STS-IE, APORTEI, and ICE-PCS scores. A cross-validation analysis was performed on the score with the best area under the curve (AUC). The 30-day survival was 96.5% (95%CI 91-98%). The score with worse area under the curve (AUC = 0.6) was the STS-IE score, while the higher was for the RISK-E score (AUC = 0.89). The AUC of the majority of risk scores suggested acceptable performance; however, statistically significant differences in expected versus observed mortalities were common. The cross-validation analysis showed that a large number of survivors (> 75%) would not have been operated if arbitrary high-risk threshold estimates had been used to deny surgery. The observed mortality in our cohort is significantly lower than is predicted by contemporary risk scores. Despite the reasonable numeric performance of the analyzed scores, their utility in judging the operability of a given patient remains questionable, as demonstrated in the cross-validation analysis. Future guidelines may advise that denial of surgery should only follow a highly experienced Endocarditis Team evaluation.

Anatomical study between the correlation of the arcuate eminence and the superior semicircular canal.

OBJECTIVE: To study the anatomical correlation between the arcuate eminence and the superior semicircular canal. MATERIAL AND METHODS: A study of the height of the arcuate eminence was carried out in 295 temporal bones. In addition, 30 temporals with different heights of the arcuate eminence (10 flat, 10 prominent and 10 very prominent) were randomly selected and radiological tests were performed by computed tomography (Pöschl projection) and subsequent dissection by milling until the apex of the superior semicircular canal was found, establishing, with both methods, the anatomical relationship with the arcuate eminence. RESULTS: The arcuate eminence was classified as: smooth, when there was no relief (1.7%); flat, measured less than 1 mm (20.3%), prominent, measured between 1 and 2 mm, in (62%), and very prominent, measured above 2 mm (12.6%). The tomographic study (CT) and its subsequent dissection by bone milling showed a direct relationship between the arcuate eminence and the semicircular canal only when it was flat, while the rest of the types corresponded to the presence of pneumatized peri-labyrinthine cells and/or cancellous bone without a direct anatomical relationship with the apex of the superior semicircular canal. CONCLUSION: The correlation between the arcuate eminence and the superior semicircular canal is direct only when it is flat (1 mm), being related to peri-labyrinthine cells and/or cancellous bone when the arcuate eminence is prominent or very prominent.

Long telomeres are associated with clonality in wild populations of the fissiparous starfish Coscinasterias tenuispina.

Telomeres usually shorten during an organism's lifespan and have thus been used as an aging and health marker. When telomeres become sufficiently short, senescence is induced. The most common method of restoring telomere length is via telomerase reverse transcriptase activity, highly expressed during embryogenesis. However, although asexual reproduction from adult tissues has an important role in the life cycles of certain species, its effect on the aging and fitness of wild populations, as well as its implications for the long-term survival of populations with limited genetic variation, is largely unknown. Here we compare relative telomere length of 58 individuals from four populations of the asexually reproducing starfish Coscinasterias tenuispina. Additionally, 12 individuals were used to compare telomere lengths in regenerating and non-regenerating arms, in two different tissues (tube feet and pyloric cecum). The level of clonality was assessed by genotyping the populations based on 12 specific microsatellite loci and relative telomere length was measured via quantitative PCR. The results revealed significantly longer telomeres in Mediterranean populations than Atlantic ones as demonstrated by the Kruskal-Wallis test (K=24.17, significant value: P-value<0.001), with the former also characterized by higher levels of clonality derived from asexual reproduction. Telomeres were furthermore significantly longer in regenerating arms than in non-regenerating arms within individuals (pyloric cecum tissue: Mann-Whitney test, V=299, P-value<10(-6); and tube feet tissue Student's t=2.28, P-value=0.029). Our study suggests that one of the mechanisms responsible for the long-term somatic maintenance and persistence of clonal populations is telomere elongation.

Anatomical and genetic study of an ancient animal tooth showing brachyodont and hypsodont mixed taxonomical characteristics.

A non-human dental piece was found in a Roman Empire tomb dated the 3rd century A.C. in Zaragoza (Spain). The morphology of this piece showed mixed brachyodont (carnivores) and hypsodont (herbivores) characteristics. As a result, the taxonomical assignation of the piece was impossible. Therefore, a protocol based on the DNA sequence of the cytochrome c oxidase subunit 1 mitochondrial region (COI) was applied. For this purpose, a pair of primers able to amplify this region in a large variety of animals was designed. The results point to a species of the Genus Bos (Family Bovidae). This assignation was later confirmed by these quencing of a short fragment of the mitochondrial D-loop region. A complete morphological description of the tooth is presented together with the DNA sequence study and comparison protocol.

[Glomus tumor of subungual presentation in the thumb and use of ultrasound in its diagnosis. Case report and literature review]. / Tumor glómico de presentación subungueal en pulgar y uso de ecografía en su diagnóstico. Reporte de caso y revisión de bibliografía.

INTRODUCTION: the glomus tumor is a benign neoplasm originated in the smooth muscle cells of the vascular glomus. Approximately 80% of lesions are located on the upper extremity and, of these, the majority are in the subungual area. The diagnosis must include imaging tests, among which ultrasound stands out, being a good alternative due to its low cost and accessibility. OBJECTIVE: we present a case of late diagnosis of surgically managed glomus tumor, as well as a review of the existing literature for diagnosis, treatment, and prognosis of this uncommon pathology. CLINICAL CASE: the case of a 52-year-old female patient who reported chronic, burning pain, radiating to the distal phalanx of the thumb with no history of trauma, of 2 years of evolution and which limited her daily life activities, is presented. The exploration with interphalangeal Doppler ultrasound is complemented, being an excellent alternative due to its easy accessibility. A glomus tumor was diagnosed in the interphalangeal thumb. An "H" approach was performed on the interphalangeal fold with subungual dissection with resection of the tumor piece and follow-up by an outpatient clinic where a surgical wound with adequate healing was found. Physical examination with capacity for the mobilization of the distal interphalangeal joint (IFJ) and visual analogue scale (VAS) 1 point. The updated pathological evaluation of the existence of a glomus tumor. CONCLUSIONS: ultrasound is an excellent aid in the diagnosis, as well as in the surgical planning for the treatment of the glomus tumor; for being accessible, low cost and highly effective. The anatomopathological study is the gold standard.

INTRODUCCIÓN: el tumor glómico es una neoplasia benigna originada en las células musculares lisas del glomus vascular. Aproximadamente 80% de las lesiones se localiza en la extremidad superior y, de éstas, la mayoría se sitúa en la zona subungueal. El diagnóstico debe incluir exámenes de imágenes, entre los que destaca la ecografía, siendo una buena alternativa por su bajo costo y accesibilidad. OBJETIVO: presentamos un caso de diagnóstico tardío de tumor glómico manejado quirúrgicamente, así como revisión de la literatura existente para diagnóstico, tratamiento y pronóstico de esta patología poco común. CASO CLÍNICO: paciente femenino de 52 años que refería un dolor crónico, ardoroso, irradiado hacia falange distal del pulgar sin antecedente traumático, de dos años de evolución y que limitaba actividades de su vida diaria. Se complementa exploración con ultrasonido Doppler interfalángico siendo una excelente alternativa por su fácil accesibilidad. Se diagnostica tumor glómico en interfalángica pulgar. Se realiza abordaje en "H" sobre pliegue interfalángico con disección subungueal con resección de pieza tumoral y seguimiento por consulta externa donde se encuentra herida quirúrgica con adecuada cicatrización. Exploración física con capacidad para la movilización de movilización de la articulación interfalángica distal (IFD) y escala visual análoga (EVA) de 1 punto. La evaluación anatomopatológica informó la existencia de tumor glómico. CONCLUSIONES: la ecografía es una excelente ayuda en el diagnóstico, así como en la planificación operatoria para el tratamiento del tumor glómico, por ser accesible, de bajo costo y de alta efectividad. El estudio anatomopatológico es el estándar de oro que da la certeza diagnóstica.

Effect of exercise intensity on albuminuria in adolescents with Type 1 diabetes mellitus.

AIMS: Exercise may be useful to detect patients with diabetes prone to develop persistent microalbuminuria. We studied the relationship between exercise intensity, measured as maximal oxygen consumption (VO(2)max), and microalbuminuria in patients with Type 1 diabetes mellitus patients. METHODS: We studied 10 patients, age range 10-18 years, with Type 1 diabetes who were normotensive and normoalbuminuric, with less than 10 years since diagnosis. Patients had normal renal function, without infections or clinical evidence of complications. Metabolic control was intensively adjusted in all patients. They underwent three consecutive physical exercise tests, reaching 100, 80 and 60% of the maximal cardiac frequency response. RESULTS: Eight patients had adequate to regular metabolic control. All patients had lower than predicted VO(2)max values. At 60%, only three patients showed microalbuminuria in excess of 20 µg/min, two of them had inadequate metabolic control. Post-exercise microalbuminuria exceeded normal values in nine, seven and three patients when submitted to 100, 80 and 60% of exercise intensity, respectively. CONCLUSIONS: Microalbuminuria increased with exercise intensity. Sex, body composition and VO(2)max were the main factors associated with microalbuminuria. The prognostic significance of albuminuria induced by intense exercise in these subjects with Type 1 diabetes is not yet known.

[Cervical vertebral hemangioma with aggressive behavior]. / Hemangioma vertebral cervical con comportamiento agresivo.

INTRODUCTION: Hemangiomas are the most common primary tumors of the spine. Mainly asymptomatic Incidental finding when performing an imaging study. The incidence reported at autopsies is 11% in the spine, multifocal lesions are present in 25 to 30% of cases. CLINICAL CASE: Vertebral cervical hemangioma with benign and stable characteristics that underwent surgical treatment, observing aggressive post-surgical behavior two months later. CONCLUSION: The approach to vertebral pathology is algorithmic and protocolized, it is necessary to determine the treatment based on the overall understanding of the disease and according to the clinical practice guidelines.

INTRODUCCIÓN: Los hemangiomas son los tumores primarios más comunes de la columna, principalmente asintomáticos, de hallazgo incidental al realizar un estudio de imagen. La incidencia reportada en autopsias es de 11% en la columna y lesiones multifocales en 25 a 30% de los casos. CASO CLÍNICO: Hemangioma cervical vertebral con características benignas y estables. Se realizó tratamiento quirúrgico, observando un comportamiento agresivo postquirúrgico dos meses después. CONCLUSIÓN: El abordaje de la patología vertebral es algorítmico y protocolizado, es necesario determinar el tratamiento con base en la comprensión global de la enfermedad y de acuerdo a las guías de práctica clínica.

Association between superior semicircular canal dehiscence and other dehiscences in temporal bone.

BACKGROUND: The study of the association between superior semicircular canal and other dehiscences in the temporal bone. MATERIALS AND METHODS: We have studied computed tomography of radiologically diagnosed people with superior or posterior semicircular canal dehiscences, in four health centres. In addition, we have studied one isolated human temporal bone, one skull and one cadaver head belonging to the collection of the Department of Human Anatomy and Histology of the University of Zaragoza that had dehiscence in the superior semicircular canal. RESULTS: The most frequent association that we observed was between superior semicircular canal dehiscence and tegmen tympani dehiscence (37.33%). Three cases (two clinical cases and one isolated temporal bone) showed multiple associated dehiscences (tegmen tympani, mastoid antrum, posterior semicircular canal, internal auditory canal, glenoid cavity, tympanum bone and geniculate ganglion) associated with superior semicircular canal dehiscence. CONCLUSIONS: When the superior semicircular canal dehiscence is associated to other in the petrous bone (tegmen tympani, mastoid antrum, posterior semicircular canal, internal auditory canal) could be grouped into the same syndrome called "otic capsule syndrome", since they have the same origin and common aetiology (otic capsule).

[Bruns Garland syndrome. Report of a case and differential diagnosis with cauda equina syndrome]. / Síndrome de Bruns Garland. Informe de un caso y diagnóstico diferencial con el síndrome de cauda equina.

BACKGROUND: The Bruns Garland syndrome (diabetic amyotrophy) it is a very rare condition, with few cases reported in the literature. Clinical differentiation of diabetic amyotrophy or cauda equine syndrome may be difficult. The issue of misdiagnosis has been discussed as a reason for poor outcome after lumbar spine surgery. We report a case of diabetic amyotrophy that mimics a cauda equina syndrome. CASE DESCRIPTION: A 59 years old man diabetic patient that suddenly begins with weakness of lower extremities and loss of sphincters control. The patient was seen in the emergency room, the anteroposterior and lateral radiographs of the lumbosacral spine evidenced spondylolisthesis L5-S1 level II of Meyerding. However, the MRI show no vertebral canal compression, nerve root compression or disc extrusion. Electrodiagnostic study revealed diabetic amyotrophy (Bruns Garland syndrome). The patient rapidly improves with treatment based in antineuritics, diabetes control, physical therapy and rehabilitation. Four months after the diagnosis he recover his muscle strength, has no alterations in the march, no loss of balance, his sensitive is preserved and has no pain. CONCLUSION: Electrodiagnostic and radiologic studies should be used in every diabetic patient presenting with leg pain and/or weakness to differentiate diabetic neuropathy from cauda equina syndrome. Treatment of both diseases may be needed for relief of the patients pain.

ANTECEDENTES: El síndrome de Bruns Garland (amiotrofia diabética) es una condición con pocos casos reportados en la literatura. La diferenciación clínica de una amiotrofia diabética o un síndrome de cauda equina puede ser difícil. El problema de un mal diagnóstico ha sido discutido como una razón para un mal resultado después de una cirugía de la columna lumbar. Se presenta un caso de amiotrofia diabética que imita un síndrome de cauda equina. DESCRIPCIÓN DEL CASO: Masculino de 59 años de edad con diabetes, comienza repentinamente con debilidad en las extremidades inferiores y pérdida del control de los esfínteres. Este paciente fue atendido en la sala de urgencias, las radiografías anteroposterior y lateral de la columna lumbosacra evidenciaron espondilolistesis L5-S1 nivel II de Meyerding. Sin embargo, la IRM no mostró ninguna compresión del canal vertebral, compresión de la raíz nerviosa, ni extrusión del disco. El estudio de electrodiagnóstico reveló amiotrofia diabética (síndrome de Bruns Garland). El paciente rápidamente mejoró con el tratamiento basado en antineuríticos, control diabético, terapia física y rehabilitación. Cuatro meses después del diagnóstico, el paciente recuperó su fuerza muscular, no mostró alteraciones en la marcha, ni pérdida del equilibrio, su sensibilidad se conserva y no manifiesta dolor. DISCUSIÓN: Deberán utilizarse estudios de electrodiagnóstico y radiológicos en todo paciente diabético que presente dolor en la pierna y/o debilidad para diferenciar una neuropatía diabética de un síndrome de cauda equina. El tratamiento en ambas enfermedades puede ser necesario para aliviar el dolor del paciente.

Echocardiographic, electrocardiographic and blood pressure changes induced by icodextrin solution in diabetic patients on peritoneal dialysis.

The use of icodextrin as an osmotic agent in solutions for peritoneal dialysis (PD) has important cardiovascular effects related with better control of extracellular volume. Among them, reduction of arterial pressure and an improvement in echocardiographic parameters stand out. In diabetic patients, icodextrin has additional potential advantages related with better metabolic control. In a multicenter, open-label randomized controlled trial, the effects of icodextrin solutions were compared to glucose solutions on echocardiographic, electrocardiographic, and blood pressure changes in diabetic patients on PD. Two phases were noted in the follow-up. In the early phase (6 months), reduction in ambulatory blood pressure (ABP) and left ventricular end diastolic diameter were found in the icodextrin group. These changes correlated with changes in body fluids. In the late phase (12 months), a trend towards baseline values in ABP was seen. Changes in inferior vena cava diameter and in low frequency R-R variability spectral analysis in the icodextrin group suggest that icodextrin increases circulating blood volume and sympathetic tone, probably by accumulation of icodextrin metabolites in the bloodstream and improvement in diabetic neuropathy as a result of lower peritoneal glucose absorption. The effects of icodextrin in diabetic patients were related to better fluid management and metabolic control.

Videoconferencias para residentes de Histología en la Universidad de Ciencias Médicas de Sancti Spíritus

Fundamento: No se conoce cómo aceptan los residentes de Histología la inclusión de un sistema de videoconferencias sobre la estructura microscópica del cuerpo humano en su estrategia de autoaprendizaje.Objetivo: Explorar en profundidad la experiencia de los residentes de Histología de la Universidad de Ciencias Médicas de Sancti Spíritus que utilizaron un sistema de videoconferencias para su formación profesional.Metodología: Estudio cualitativo en el que se realizó una entrevista a profundidad con los especialistas y residentes de Histología que han utilizado el sistema de videoconferencias en la Universidad de Ciencias Médicas de Sancti Spíritus. Se transcribieron las entrevistas, se codificaron y se seleccionaron los principales temas abordados.Resultados: Se entrevistaron 5 usuarios del sistema de videoconferencias; de la entrevista surgieron 5 temas: 1) Como los residentes insertan las videoconferencias en su estrategia de autoaprendizaje, 2) Preferencia de las videoconferencias sobre los libros de texto, 3) Aciertos y desaciertos de las videoconferencias, 4) ¿Qué aportan las videoconferencias a la formación del residente, ventajas y desventajas? y 5) Sugerencias para mejorar las videoconferencias.Conclusiones: Un sistema de videoconferencias sobre la estructura microscópica del cuerpo humano puede ocupar un papel protagónico en la estrategia de aprendizaje de residentes de Histología. La preferencia que muestran los residentes por las videoconferencias sobre otros medios didácticos puede estar asociada a la capacidad de la multimedia para disminuir la carga cognitiva y facilitar el aprendizaje cuando se siguen los principios de Mayer al elaborar estos medios. La presencia de imágenes digitales en estas videoconferencias fue clave para su aceptación. [AU]

Effects of the antiestrogens tamoxifen, toremifene, and ICI 182,780 on endometrial cancer growth.

BACKGROUND: Tamoxifen has been shown to promote the growth of human endometrial tumors implanted in athymic mice, and it has been associated with a twofold to threefold increase in endometrial cancer. Toremifene, a chlorinated derivative of tamoxifen, and ICI 182,780, a pure antiestrogen, are two new antiestrogens being developed for the treatment of breast cancer. The effects of these drugs on endometrial cancer are currently unknown. Our objective was to evaluate the effects of toremifene and ICI 182,780 on the growth of human endometrial cancer in athymic mice. METHODS: Athymic, ovariectomized mice were implanted with human endometrial tumors and treated with estrogen, tamoxifen, or the new antiestrogens. RESULTS: The effects of tamoxifen and toremifene on the growth of either tamoxifen-stimulated or tamoxifen-naive endometrial tumors in athymic mice were not substantially different. ICI 182,780 inhibited the growth of tamoxifen-stimulated endometrial cancer, in both the presence and the absence of estrogen. CONCLUSIONS: Toremifene and tamoxifen produce identical effects in our endometrial cancer models. Therefore, it is possible that toremifene, like tamoxifen, may be associated with an increased incidence of endometrial cancer. In contrast, ICI 182,780 inhibited tamoxifen-stimulated endometrial cancer, both in the presence and in the absence of estrogen, suggesting that this drug may be safe with regard to the endometrium, even if it is used following tamoxifen, and that it may not result in an increased incidence of endometrial cancer. Indeed, it is even possible that ICI 182,780 may prove useful as an adjuvant agent in early stage endometrial cancer.

[Determination of factors conditioning adherence and accomplishment of renal protection diet in patients with chronic renal failure: pilot study for the elaboration of a dietary guideline]. / Determinación de los factores condicionantes en la adhesión y cumplimiento de la dieta de protección renal en pacientes con insuficiencia renal crónica: estudio previo para la elaboración de una guía dietética.

There are seldom studies on dietary behavior of patients with chronic renal failure (CRF). The aim of this study has been to know, by means of a previously validated questionnaire, which are the psycho-sociocultural factors that affect, and to what extent, assumption and adherence the dietary therapy while determining the degree of disease perception and several factors related with it. The study population is comprised by 81 patients from the nephrology clinic of the "12 de Octubre" Hospital of Madrid, with CRF in a pre-dialysis status. Seventy-seven point seventy-four percent answered "well" or "very well" to questions relating to disease knowledge and perception. Emotional and auto-management factors have little relevance according to 69.87% of patients. Fifty-nine point twenty-six percent feel a high level of familial support, and 35.77% alters dietary behavior when environmental conditions change. Most of the interviewees (87.65%) do not have difficulties finding the prescribed foods, and 70.37% considers their cost is not excessive. For almost half of the patients (48.76%), renal protection diet represents a variation in their dietary habits, a similar percentage expresses difficulty with elaboration. Food palatability is not a problem in 67.90% of the cases. Fifty-one point twenty-four percent does not perceive difficulty with cooking procedures. Seventy point ninety-nine percent feels support in one way or the other, by health care staff, although just 56.79% reports that the diet has not been explained to them. Only 18.51% questions the diet effectiveness as regards to their disease course. As for the gender variable, there were significant differences (p < 0.05), with a higher influence on men, in sections relating to disease knowledge, and influence of apathy and family support, the women those having the highest scores for food management, diet transgression at family meetings, and less information received about the prescribed diet. As for family support, there are significant differences only by age groups, patients aged more than 65 years being those feeling more this psychological support. The group of patients with a creatinine clearance less than 25 mL/min is the one expressing less categorically their appreciation on diet effectiveness. There are factors in which significant difficulty percentages are observed and that may induce diet transgression, in some cases without the patient being completely aware of, such as environmental changes, change in traditional habits, the degree of diet explanation, the organoleptic characteristics, and the lack of knowledge of appropriate cooking procedures. All these indicators confirm the need for enhancing nutritional education of these patients and their family environment, also showing the need for a nutritional intervention that completely supports patients in the process of adaptation and maintenance of their new dietary habit.

Oleandrin suppresses activation of nuclear transcription factor-kappaB, activator protein-1, and c-Jun NH2-terminal kinase.

Agents that can suppress the activation of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) may be able to block tumorigenesis and inflammation. Oleandrin, a polyphenolic cardiac glycoside derived from the leaves of Nerium oleander, is a candidate NF-kappaB and AP-1 modulator. We investigated the effect of oleandrin on NF-kappaB activation induced by inflammatory agents. Oleandrin blocked tumor necrosis factor (TNF)-induced activation of NF-kappaB in a concentration- and time-dependent manner. This effect was mediated through inhibition of phosphorylation and degradation of IkappaBalpha, an inhibitor of NF-kappaB. A proprietary hot water extract of oleander (Anvirzel) also blocked TNF-induced NF-kappaB activation; subsequent fractionation of the extract revealed that this activity was attributable to oleandrin. The effects of oleandrin were not cell type specific, because it blocked TNF-induced NF-kappaB activation in a variety of cells. NF-kappaB-dependent reporter gene transcription activated by TNF was also suppressed by oleandrin. The TNF-induced NF-kappaB activation cascade involving TNF receptor 1/TNF receptor-associated death domain/TNF receptor-associated factor 2/NF-kappaB-inducing kinase/IkappaBalpha kinase was interrupted at the TNF receptor-associated factor 2 and NF-kappaB-inducing kinase sites by oleandrin, thus suppressing NF-kappaB reporter gene expression. Oleandrin blocked NF-kappaB activation induced by phorbol ester and lipopolysaccharide. Oleandrin also blocked AP-1 activation induced by TNF and other agents and inhibited the TNF-induced activation of c-Jun NH2-terminal kinase. Overall, our results indicate that oleandrin inhibits activation of NF-kappaB and AP-1 and their associated kinases. This may provide a molecular basis for the ability of oleandrin to suppress inflammation and perhaps tumorigenesis.

A phase I study of high-dose tamoxifen for the treatment of refractory malignant gliomas of childhood.

Recent studies have indicated that the proliferation of malignant gliomas is in part dependent on excessive activation of protein kinase C (PKC)-mediated pathways. Conversely, inhibiting PKC may provide a novel approach for blocking glioma growth. The antiestrogen tamoxifen, a moderately potent PKC inhibitor, has been shown in vitro to block the proliferation of malignant glioma cell lines at concentrations several-fold higher than those typically attained during the treatment of breast cancer; such serum concentrations may be achieved with doses > 40 mg/m2 b.i.d. The safety and efficacy of these high doses for producing disease control in patients with malignant gliomas has recently been noted anecdotally, although a rigorous study of this agent has been lacking. To address this issue, we examined the safety and efficacy of high-dose tamoxifen in a series of children with malignant gliomas that had progressed after conventional therapy. An initial group was treated with 60 mg/m2 p.o. b.i.d. and a second group with 100 mg/m2 b.i.d. Steady-state serum tamoxifen and metabolite levels were measured in most patients. Toxicity with the regimen was minimal; two patients treated at the higher dose required reduction to the lower dose because of asymptomatic prolongation of the QT interval on an electrocardiogram. Although none of the patients exhibited clear-cut tumor regression, 4 of 14 patients had stabilization of previously progressive disease for at least 3 months; the longest survivor lived for 17 months after beginning tamoxifen. The moderate efficacy of this agent in otherwise end-stage disease coupled with its low toxicity and the relative ease of oral administration provides a rationale for proceeding with larger studies of this agent in patients with malignant gliomas, possibly as a means for potentiating the effects of conventional chemotherapeutic agents, which to date have shown limited efficacy in the treatment of these tumors.

Implantation of iris devices in congenital and traumatic aniridias: surgery solutions and complications.

PURPOSE: To show surgical solutions in patients with traumatic and congenital aniridia, to evaluate the clinical improvement of these patients when iris prosthesis are implanted, and to examine safety and complications of these implants in a long-term follow-up. METHODS: Eight patients were included in this retrospective noncomparative case series. Nine eyes had an artificial iris implantation for traumatic or congenital aniridia. Three eyes received a black diaphragm intraocular lens (IOL) in capsular bag after phacoemulsification. An aniridia prosthesis, sulcus sutured, in front of a previous IOL was implanted in two eyes. A black diaphragm IOL, sulcus sutured, in two eyes; two iris diaphragm rings, in front of the previous IOL, in one eye; and a sector iris prosthesis in front of an IOL in the last eye were implanted. Mean follow-up was 22.5 months (range 16 to 44 months). RESULTS: All patients had improved visual acuity (VA) and visual comfort after surgery. The glare disability was subjectively better in all cases. Two patients developed new ocular hypertension after surgery; one of them was controlled by medical treatment and the other needed cyclodiode. Two of the patients with glaucoma preoperatively also needed cyclodiode procedure and one of them an Ahmed valve. CONCLUSIONS: Several kinds of artificial iris implants are available. In all our patients with aniridia, iris artificial prostheses improved VA and diminished visual discomfort. Glaucoma is the most important complication after artificial iris implant. It is possible to implant the iris prosthesis in the capsular bag, but this requires a large capsulorrhexis and presents a surgical challenge.

Effects of angiogenesis inhibitor TNP-470 on tamoxifen-stimulated MCF-7 breast tumors in nude mice.

The antitumor effect of TNP-470, antiangiogenic drug, was analyzed in the tamoxifen-stimulated MT-2 tumors inoculated in the athymic nude mice. TNP-470 was injected subcutaneously at a dose of 30 mg/kg body weight twice a week to mice which were randomized into three treatments: control (sham treatment), tamoxifen alone, and tamoxifen plus TNP-470. TNP-470 inhibited the growth of the tamoxifen-stimulated MT2 tumors without any major side effects or significant weight loss compared with tamoxifen-treated mice alone. The mean tumor area of the mice treated with tamoxifen plus TNP-470 was reduced 50% to those treated with tamoxifen alone. TNP-470 was shown to inhibit tumor neovascularization and to increase incidence of apoptosis in tumor cells. TNP-470 did not affect tamoxifen metabolism of the mice. In conclusion, TNP-470 could be evaluated clinically in patients with tamoxifen failure.

Putative dengue virus receptors from mosquito cells.

Dengue viruses are arthropod-borne, single-stranded RNA viruses. Aëdes aegypti and Aëdes albopictus are the principal vectors. In order to understand the molecular basis of dengue virus infections we explored the biochemical identity of dengue-2 (DEN-2) virus receptors in the Aëdes albopictus-derived cell line C6/36. We show here that DEN-2 interacts with two major polypeptides of 80 and 67 kDa. Polyclonal anti-C6/36 membrane antibodies block DEN-2 binding to intact C6/36 monolayers as well as to membrane extracts. Our results strongly suggest that the identified polypeptides are part of the DEN-2 receptors.

Reproducibility of digital image analysis for measuring corneal haze after myopic photorefractive keratectomy.

PURPOSE: To evaluate the usefulness of digital image analysis for quantifying corneal haze by determining the reproducibility of its measurements at the corneal plane. METHODS: In a prospective study, 20 randomly selected eyes that had undergone myopic photorefractive keratectomy were photographed focusing the slit beam on their anterior corneal surface. Each photograph was examined using computer image analysis techniques that detect the edge of the reticular pattern of the image. Quantification of the difference between two areas, treated and adjacent untreated cornea, each containing 3,750 pixels with a resolution of 256 gray levels, was performed. Intra-analyzer variation was determined by evaluating the photographs obtained by two analyzers under standard conditions on four separate visits. Interanalyzer variation was calculated using one measurement and the mean of the four measurements. RESULTS: The pooled standard deviation of the measurements for the analyzers was 0.63 and 0.62 gray levels (coefficient of variation, 4.1% and 3.3%). An association between less severe haze measurements and higher reproducibility scores was found (r = .42; P = .007). The mean interanalyzer variation was smaller for the average of four measurements, 0.55 +/- 0.37 gray levels, than for one measurement, 0.94 +/- 0.73 gray levels (P = .014). CONCLUSIONS: Good reproducibility for haze measurements by digital image analysis of the differences between the treated and adjacent untreated corneal areas was obtained. When the average of four measurements was used instead of a single measurement, interanalyzer reproducibility increased significantly. This new technique may be used to quantify and analyze corneal haze after myopic photorefractive keratectomy.