Enabling a bioinspired N,N,N-copper coordination motif through spatial control in UiO-67: synthesis and reactivity.

Metal-organic frameworks (MOFs) featuring zirconium-based clusters are widely used for the development of functionalized materials due to their exceptional stability. In this study, we report the synthesis of a novel N,N,N-ligand compatible with a biphenyl dicarboxylic acid-based MOF. However, the resulting copper(I) complex exhibited unexpected coordination behaviour, lacking the intended trifold coordination motif. Herein, we demonstrate the successful immobilization of a bioinspired ligand within the MOF, which preserved its crystalline and porous nature while generating a well-defined copper site. Comprehensive spectroscopic analyses, including X-ray absorption, UV/Vis, and infrared spectroscopy, were conducted to investigate the copper site and its thermal behaviour. The immobilized ligand exhibited the desired tridentate coordination to copper, providing access to a coordination motif otherwise unattainable. Notably, water molecules were also found to coordinate to copper. Upon heating, the copper centre within the MOF exhibited reversible dehydration, suggesting facile creation of open coordination sites. Furthermore, the copper site displayed reduction at elevated temperatures and subsequent susceptibility to oxidation by molecular oxygen. Lastly, both the molecular complexes and the MOF were evaluated as catalysts for the oxidation of cyclohexane using hydrogen peroxide. This work highlights the successful immobilization of a bioinspired ligand in a zirconium-based MOF, shedding light on the structural features, thermal behaviour, and catalytic potential of the resulting copper sites.

Immunotolerance induction effectivity in hemophilia A children and neutralizing alloantibodies. / Efectividad de inducción de tolerancia inmune en niños con hemofilia A y aloanticuerpos neutralizantes.

INTRODUCTION: The development of anti-factor VIII neutralizing antibodies in hemophilia A is the most severe com plication related to treatment. Immune tolerance induction (ITI) is the only known treatment for eradicating inhibitors. A successful ITI allows using factor VIII (FVIII) again for the treatment or prophylaxis of hemorrhagic events. OBJECTIVE: To report the experience of pediatric patients who underwent ITI in the country's public health care network. PATIENTS AND METHOD: Retrospective and descriptive analysis of 13 pediatric patients with severe Hemophilia A and high-titer inhibitors persis tence who underwent ITI and complete follow-up. Plasma-derived FVIII concentrate was used at 70 180 IU/kg/day doses. The success of the treatment is defined by achieving a negative titer and a half life recovery of the FVIII. The results were expressed in median (range). RESULTS: In 13 patients, the inhibitor was identified at an average age of 17.6 months, after 35.2 days of exposure to the FVIII. 11 patients (84.6%) recovered the half-life of FVIII after 49.6 months of treatment. In the patients who responded to treatment, the inhibitor titer was negative at 6 months on average. CONCLUSIONS: ITI is the treatment of choice for patients with hemophilia A and inhibitors persistence. ITI must be perso nalized since the time response is variable in each patient.

Efectividad de inducción de tolerancia inmune en niños con hemofilia A y aloanticuerpos neutralizantes / Immunotolerance induction effectivity in hemophilia A children and neutralizing alloantibodies

Resumen: Introducción: El desarrollo de aloanticuerpos neutralizantes anti-factor VIII en hemofilia A es la complicación más seria relacionada al tratamiento. La inducción de tolerancia inmune (ITI) o inmunotolerancia es el único tratamiento que erradica inhibidores, permitiendo utilizar nuevamente factor VIII para el tratamiento o profilaxis de eventos hemorrágicos. Objetivo: reportar la experiencia en niños sometidos a inmunotolerancia en la red pública del país. Pacientes y Método: Análisis retrospectivo y descriptivo de 13 niños con Hemofilia A severa e inhibidores persistentes de alto título, que recibieron ITI y seguimiento completo. Se utilizó concentrado de FVIII plasmático en dosis de 70-180 UI/Kg/diarias, definiendo éxito como la negativización del inhibidor y recu peración de la vida media del FVIII. Resultados expresados en media (rango). Resultados: En 13 pacientes se identificó el inhibidor, a una edad de 17,6 meses (2-48), tras 35,2 días (9-112) de exposición a FVIII. Once pacientes (84,6%) recuperaron la vida media del FVIII, tras 49,6 meses (26-70) de tratamiento. En los pacientes que respondieron, el título del inhibidor se negativizó en 7,3 meses (1-20). Conclusiones: En niños con hemofilia A e inhibidores persistentes de alto título, la ITI tiene un elevado éxito. Dado que el tiempo de respuesta es variable, la inmunotolerancia debe ser personalizada.

Abstract: Introduction: The development of anti-factor VIII neutralizing antibodies in hemophilia A is the most severe com plication related to treatment. Immune tolerance induction (ITI) is the only known treatment for eradicating inhibitors. A successful ITI allows using factor VIII (FVIII) again for the treatment or prophylaxis of hemorrhagic events. Objective: To report the experience of pediatric patients who underwent ITI in the country's public health care network. Patients and Method: Retrospective and descriptive analysis of 13 pediatric patients with severe Hemophilia A and high-titer inhibitors persis tence who underwent ITI and complete follow-up. Plasma-derived FVIII concentrate was used at 70 180 IU/kg/day doses. The success of the treatment is defined by achieving a negative titer and a half life recovery of the FVIII. The results were expressed in median (range). Results: In 13 patients, the inhibitor was identified at an average age of 17.6 months, after 35.2 days of exposure to the FVIII. 11 patients (84.6%) recovered the half-life of FVIII after 49.6 months of treatment. In the patients who responded to treatment, the inhibitor titer was negative at 6 months on average. Conclusions: ITI is the treatment of choice for patients with hemophilia A and inhibitors persistence. ITI must be perso nalized since the time response is variable in each patient.

Single-Center Long-Term Follow-Up of Kidney Donors in Argentina (Hospital Italiano de Buenos Aires).

INTRODUCTION: Living kidney donor (LKD) transplantation is increasing due to organ shortage. Clinical studies have shown that the risk of developing end-stage renal disease (ESRD) in donors is similar to that in the general population. Our goal was to evaluate postdonation renal outcomes assessed by glomerular filtration rate (GFR), proteinuria, and blood pressure. METHODS: A total of 210 LKD transplants were performed at Hospital Italiano de Buenos Aires between 2000 and 2014. Postdonation outcomes were analyzed in 109 donors. GFR was assessed by 24-hour creatinine clearance (as 24-hour ClCr) and estimated using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Additionally, we correlated the predonation renal functional reserve (RFR) with postdonation GFR. Donor results were compared to the expected GFR (adjusted to age and single kidney). Other renal outcome indicators measured were albuminuria and blood pressure, and they were compared (predonation and postdonation) using univariate analysis. RESULTS: A total of 109 patients were followed up for 47 ± 34 months (range, 12-168): 70% were female, age at donation was 48.58 years (range, 25-70), and predonation serum creatinine was 0.85 ± 0.17 mg/dL. Postnephrectomy GFR (24-hour ClCr) was significantly lower compared to predonation GFR (105.38 ± 21.78 mL/min/1.73 m2 vs 90.14 ± 17.78 mL/min/1.73 m2). However, postdonation GFR was not significantly different compared to the expected GFR. No differences were found for blood pressure or albuminuria. Age >50 and an RFR (<20%) was associated with a lower GFR. CONCLUSIONS: In this population of LKD, renal outcome (24-hour CrCl, albuminuria, and blood pressure) was within the expected outcome for healthy individuals after uninephrectomy.

Características epidemiológicas del trauma raquimedular: una comparación entre Valparaiso-Chile y Cochabamba-Bolivia / Epidemiological characteristics of spinal cord trauma: a comparison of Valparaiso-Chile-Bolivia and Cochabamba

El estudio de los traumatismos raquimedulares, tiene vital importancia por afectar una población económicamente activa, perjudicando entre otras, el crecimiento económico de las familias comprometidas, por ello; el presente estudio pretende conocer cuáles son las características epidemiológicas del trauma raquimedular; analizando la prevalencia según el sexo, grupo etareo, etiología, secuelas, manejo hospitalario, complicaciones y morbi-mortalidad entre otras variables; mediante un estudio multicéntrico comparativo, descriptivo retrospectivo, entre los centros neuro-quirúrgicos de referencia de Valparaíso-Chile y Cochabamba-Bolivia. Se revisaron 372 historias clínicas de pacientes con diagnóstico final de trauma raquimedular; correspondientes al periodo comprendido entre enero-2002 hasta junio-2010, obteniéndose los siguientes resultados: Se obtuvo una media de 3.72 + 0.12 casos por mes: el grupo etareo más afectado fue el de 15-29 años en Valparaíso y los 30-39 años en Cochabamba (28.8 por ciento; DE + 2.2), el sexo masculino es el más afectado (72.84 por ciento; DE + 3.7) siendo la causa más frecuente la caída de grandes alturas en Cochabamba y la actividad de los piqueros en el mar, en Valparaíso (28.83 por ciento; DE + 4.3), la media de estancia hospitalaria fue de 20.29 + 19.4 días en Valparaíso vs 22.16 + 11.5 días en Cochabamba, el tratamiento conservador fue el más usado en Cochabamba; sin embargo el 77.48 + 0.19 por ciento fue intervenido quirúrgicamente en Valparaíso, el 78.19 + 0.19 por ciento tuvieron una evolución favorable, la secuela más común fue la paraplejia en el 6.44 + 0.13 por ciento y la mortalidad fue del 4.5 por ciento en Valparaíso y 2.73 por ciento en Cochabamba. Llegándose a concluir que el paciente con trauma raquimedular es un varón joven económicamente activo, con estancia hospitalaria prolongada, de evolución favorable pues responde al tratamiento conservador; con riesgo de incapacidad por paraplejia.

The study of traumatic spinal cord injuries, is vitally important because it affects the economically active population, harming among others, the economic growth of the families involved, therefore, the study seeks to examine what are the epidemiological characteristics of spinal cord injuries, evaluating the prevalence according sex, age group, etiology, sequelae, hospital management, complications and morbidity and mortality among other variables, through a multicenter comparative descriptive retrospective, including neurosurgical centers for reference of Valparaiso-Chile and Bolivia-Cochabamba. We reviewed medical records of 372 patients with final diagnosis of spinal cord injury, of the period January to June 2002-2010, and the results were as follows: We obtained an average of 3.72 + 0.12 cases per month: the age group most affected was 20-29 years in Valparaiso and 30-39 years in Cochabamba (28.8 percent, SD + 2.2). The male is most affected (66.9 percent, SD + 3.7) being the most common cause from great heights in Cochabamba and the activity of the boobies in the sea in Valparaiso (36.9 percent, SD + 4.3), the average hospital stay was 20.29 + 19.4 days in Valparaiso and 22.16 +11.5 days in Cochabamba. The conservative treatment was the most used and only 12 + 2.16 percent underwent surgery, 97 + 3.3 percent had a favorable outcome, the most common sequel was the paraplegia in 6.7 + 3.2 percent of the cases, and mortality was 6.3 percent in Valparaiso and 3 percent in Cochabamba. The authors conclude that patients with spinal cord injury are most frequent in the young male economically active, with prolonged hospital stay, because of favorable response to conservative treatment, with risk of disability due to paraplegia.

Gene transfer using bovine adeno-associated virus in the guinea pig cochlea.

Gene transfer into the cells of the cochlea is useful for both research and therapy. Bovine adeno-associated virus (BAAV) is a new viral vector with potential for long-term gene expression with little or no side effects. In this study, we assessed transgene expression using BAAV with beta-actin-GFP as a reporter gene, in the cochleae of normal and deafened guinea pigs. We used two different routes to inoculate the cochlea: scala media (SM) or scala tympani (ST). Auditory brainstem response assessments were carried out before inoculation, 7 days after inoculation and immediately before killing, to assess the functional consequences of the treatment. We observed threshold shifts because of the surgical invasion, but no apparent pathology associated with the virus. Fourteen days after the injection, animals were killed and cochleae assessed histologically. Epi-fluorescence showed that BAAV transduced the supporting cells of both normal and deafened animals through SM and ST inoculations. Transgene expression in cells of the membranous labyrinth after ST inoculation is an important outcome because of the greater feasibility of this route for future clinical application. BAAV facilitates efficient transduction of the membranous labyrinth epithelium with minimum pathogenicity and may become clinically applicable for inner ear gene therapy.

Utilisation of controlled pore topology for the separation of bioparticles in a mixed-glass beads column.

To study the flow of shaped particles in porous media, elution of spherical and rod-like micro-organisms was performed through beds of spherical glass beads. A 0.04 cm/s constant flow rate was used with 5 microm yeast suspensions, 1 microm latex micro-spheres and rod-like bacilli Lactobacillus bulgaricus 6 microm long and 0.5 microm in diameter. Yeast cells' diameter is close to the bacilli length and micro-spheres have the same diameter as bacilli. All particle types have similar density. To make the different packing beds, 1.125 mm coarse beads and 0.1115 mm fine beads were used. Experiments were carried out using a column loaded with the binary packing (volume fraction of coarse particles in the mixture 0.7) or a monosize packing with the same amount of coarse or fine particles as used in the binary packing. Analysis of experimental results was based on two models: pure exclusion effect and hydrodynamic separation model [hydrodynamic chromatography (HDC)]. Results for spheres show that the classic HDC model fits to the experimental data whenever the ratio of particle size to the pathway bend scale is high ( approximately 1/100, micro-spheres). However, if this ratio increases and becomes approximately 1/20, the HDC model needs to be corrected due to the effect of channel wall curvature on exclusion. This led to a modified HDC equation of the form R=B/(1+2lambda-2.8lambda(2)), where R is the retention, lambda is the aspect ratio and constant B>or=1. Bacillus separation follows an exclusion mechanism, since pore topology is important in the separation of shaped particles when the aspect ratio approaches lambda=0.1. In the case of a binary packing bed, rod-like particles display a different behaviour than the one exhibited by the spherical particles of the same scale as bacilli, either in length or in diameter. This may be explained by the interaction between rod-like bacilli and the bed's pore topology. A generalised exclusion model for particles was proposed to be R=A/(1-lambda)(z), where A is the coefficient proportional to the tortuosity and the parameter z=1, 2 or 3 depends mainly on pore shape. Controlled pore topology opens interesting applications for bio-separation (in porous micro-fluidic devices, deep bed filtration) and might be especially important for macromolecules and micro-organisms separation with different shapes.

Surface-enhanced Raman scattering on colloidal nanostructures.

Surface-enhanced Raman scattering combines extremely high sensitivity, due to enhanced Raman cross-sections comparable or even better than fluorescence, with the observation of vibrational spectra of adsorbed species, providing one of the most incisive analytical methods for chemical and biochemical detection and analysis. SERS spectra are observed from a molecule-nanostructure enhancing system. This symbiosis molecule-nanostructure is a fertile ground for theoretical developments and a realm of applications from single molecule detection to biomedical diagnostic and techniques for nanostructure characterization.

Perfil epidemiológico de los delitos sexuales en la IX Región: enero/2001-diciembre/2003 / Epidemiological profile of sexual offences in the IX region January 2000-December 2003

Los Delitos Sexuales son actos que atentan contra la libertad de las personas e indemnidad sexual de los menores de edad. En Chile estos delitos constituyen un fenómeno permanente cuya magnitud real se desconoce. El objetivo de este estudio fue caracterizar la población víctima de agresiones sexuales según características socio-biodemográficas, tipo de delito denunciado, relación víctima-imputado, lesiones encontradas en el examen físico y hallazgos por pruebas de laboratorio. Se seleccionaron de la Unidad de Sexología Forense del Servicio Médico Legal de Temuco, 1029 casos de delitos sexuales denunciados entre Enero/2000-Diciembre 2003. Los datos se registraron en planilla Excel y analizados con el software Winstat para Excel. La distribución anual para los años 2000, 2001,2002 y 2003 fueron 17.4 por ciento, 21 por ciento, 30.8 por ciento respectivamente. Del grupo analizado un 82 por ciento era de sexo femenino con una edad promedio de 14.5 años, el 70.5 por ciento con residencia urbana, 93.4 por ciento soltero y 70.5 por ciento estudiante. El 51 por ciento de los delitos denunciados son violaciones, siendo el 61 por ciento denuncias por atentados únicos. El agresor era conocido por la víctima en un 84 por ciento. Presentaron lesiones extragenitales, genitales y coloproctológicas el 12.8 por ciento, 10.2 por ciento y 5.8 por ciento respectivamente. El 6.3 por ciento de las violaciones denunciadas presentaba espermios en la muestra de fluidos. Los delitos sexuales afectan principalmente a mujeres estudiantes del área urbana, la mayoría de las veces realizados por individuos conocidos por la víctima. A pesar del examen realizado, sólo es posible encontrar lesiones atribuibles al atentado en 1/5 de los casos y espermios en el 6.3 por ciento de las violaciones denunciadas.

Optically driven spin memory in n-doped InAs-GaAs quantum dots.

We show that the spin state of the resident electron in an n-doped self-assembled InAs-GaAs quantum dot can be written and read using nonresonant, circularly polarized optical pumping. A simple theoretical model is presented and accounts for the remarkable dynamics producing counterpolarized photoluminescence.

SALL1 expression in the human pituitary-adrenal/gonadal axis.

SALL1 was originally identified on the basis of its DNA sequence homology to the region-specific homeotic gene Sal, in Drosophila melanogaster, which acts as a downstream target of hedgehog/tumor growth factor-beta-like decapentaplegic signals. The SALL1 gene has been associated with the Townes-Brocks Syndrome (TBS), a disorder characterized by multiorgan dysgenesis including renal and genital malformations. In this study, SALL1 message production was evaluated in association with the tissue localization of the protein product of SALL1, p140. SALL1 protein expression was observed in various adult and fetal tissues which elaborate reproductive endocrine hormones. The p140 was localized in specific microanatomic sites of the pituitary, adrenal cortex and the placenta. In the human pituitary, SALL1 protein expression was limited to the adenohypophysis, where it colocalized to those cells producing GH and the gonadotropins, LH and FSH. SALL1 expression was also found in most of the fetal and adult adrenal cortex in addition to the trophoblastic cells of the placenta. This pattern of expression complements prior studies demonstrating p140 in testicular fetal Leydig cells, adult Leydig and Sertoli cells, and granulosa cells of the ovary. The SALL1 protein was also shown here to be highly expressed in trophoblast tumors, which overproduce sex hormones. The expression patterns of SALL1 at multiple levels of the reproductive endocrine axis and the phenotypic effects associated with TBS suggest that SALL1 may have an important role in the interaction of the pituitary-adrenal/gonadal axis during reproduction.

Transforming growth factor-beta is a potent inhibitor of extracellular matrix degradation by cultured human mesangial cells.

Accumulation of the glomerular extracellular matrix (ECM) is a pivotal event in the progression from acute glomerular injury to end-stage renal disease. Although enhanced ECM synthesis has been demonstrated to contribute to ECM accumulation, the role of decreased ECM degradation is largely unknown. It was previously shown that glomerular ECM degradation is mediated by a plasminogen activator (PA)/plasmin/matrix metalloproteinase 2 (MMP-2) cascade. However, little information is available regarding the factors that regulate the activity of this degradative cascade in normal or pathologic states. Transforming growth factor-beta1 (TGF-beta1) is shown here to be a potent inhibitor of ECM degradation by cultured human mesangial cells. Using human mesangial cells grown on thin films of 125I-labeled Matrigel, dose-dependent inhibition of ECM degradation in the presence of TGF-beta1 was observed, reaching >90% inhibition with 0.4 ng/ml TGF-beta1. Addition of anti-TGF-beta antibodies (4 microg/ml) in the absence of exogenous TGF-beta increased ECM degradation (1.8+/-0.2-fold versus controls, P<0.05). In contrast, platelet-derived growth factor, at concentrations up to 10 ng/ml, had no effect on ECM degradation. TGF-beta completely blocked the conversion of plasminogen to plasmin and markedly reduced the conversion of latent MMP-2 to active MMP-2. TGF-beta did not significantly alter the levels of tissue PA, total MMP-2, or tissue inhibitor of metalloproteinase-1, but did increase the levels of PA inhibitor- (1.8-fold, P<0.05), the major physiologic inhibitor of PA. These data document that TGF-beta is a potent inhibitor of ECM degradation by cultured human mesangial cells, and they suggest that decreased mesangial matrix degradation, caused by TGF-beta-mediated decreases in the activity of the PA/plasmin/MMP-2 cascade, may contribute to the glomerular matrix accumulation that occurs in progressive renal disease.

Histologic evidence of a radiosensitizing effect of Taxol in patients with astrocytomas.

The new anticancer agent Taxol appears to potentiate the effects of radiation on brain tumor cell lines in vitro and was recently evaluated by our group as a radiosensitizer in a phase I study for primary brain tumors. In that study, we administered Taxol as a three-hour IV infusion repeated every week for six weeks and gave daily cranial irradiation concurrently for a total of 6000 rads. We reviewed the charts of the 60 patients who participated in the study, and identified twelve patients who underwent a second surgery after treatment because of progressive symptoms and an enlarging intracranial mass on MRI. Pathologically, each patient showed prominent radionecrosis, and other evidence of accelerated radiation changes (confluent areas of coagulative necrosis, bizarre nuclei, marked thickening and fibrinoid changes in multiple blood vessels). These changes were noted many weeks earlier than would be expected after radiation therapy alone and were independent of age, and tumor histology. We postulate that the accelerated radiation changes may be due to the radiation sensitizing effects of Taxol. We also noted a change of the pattern of tumor recurrence, compared to historic reports, and a dose-necrosis relationship where the resected tumor is formed completely of necrotic tissue in patients who received 150 mg/m2 or higher dose of Taxol. These observations may be of significance for future study design.

The temporal profile and morphologic features of neuronal death in human stroke resemble those observed in experimental forebrain ischemia: the potential role of apoptosis.

Although neuronal death has been studied in experimental models of ischemia, the precise mechanisms regulating cell death remain unclear. Furthermore, the timing and pattern of neuronal death in human stroke has not been extensively studied. To further our understanding of ischemia-induced neuronal death, we examined the temporal profile of histochemical and morphologic characteristics of hippocampal neuronal death following experimental forebrain ischemia and compared these findings to human brain specimens obtained from subjects suffering cerebral infarction. Transient forebrain ischemia (TFI) was induced in normothermic adult rats by bilateral carotid artery occlusion combined with hypotension. Animals were sacrificed at 6, 12, 18, 24, 48, and 72 h and 7, 14, and 28 days following ischemia (n = 4 at each time point). Experimental tissue was analyzed using light and electron microscopy as well as TUNEL histochemistry. A total of 27 human brain specimens with neuropathological confirmation of ischemic damage and appropriate controls were also examined using light microscopy and TUNEL histochemistry. Dense TUNEL staining in hippocampal CA-1 neurons was present at 48 and 72 h following experimental ischemia. Prior to these times, little or no nuclear staining was noted and after 72 h nuclear staining diminished rapidly. Ultrastructural findings at these time points demonstrated many features similar to those seen in cells undergoing apoptosis, such as cell shrinkage with increased electron density, chromatin condensation with formation of heterochromatin, intact plasma membranes, and intact intracellular organelles. In a similar fashion, human stroke specimens during the subacute period showed dense nuclear TUNEL staining in penumbral neurons, whereas in the acute or chronic stages little or no staining was noted. Our results demonstrate that the timing of morphologic changes and TUNEL histochemistry following human stroke resembles that observed in experimental TFI. Furthermore, neuronal death in both experimental ischemia and human stroke share several features characteristic of apoptotic cell death.

Third ventricular chordoid glioma: a distinct clinicopathologic entity.

We have encountered a series of 8 third ventricular neoplasms with a distinctive chordoid appearance that appear to represent a clinicopathologic entity. The tumors occurred in 7 females and 1 male, ranging in age from 31 to 70 years. In all cases, imaging studies showed a large well-circumscribed third ventricular mass; a cystic component was noted in 2. The tumors consisted of cords and clusters of cohesive, oval-to-polygonal epithelioid cells with abundant eosinophilic cytoplasm, relatively uniform round-to-oval nuclei, and inconspicuous nucleoli. Mitotic activity was absent. The stroma consisted of scant, coarse fibrillar processes, as well as prominent, slightly basophilic, extracellular mucin resembling that in chordomas. Throughout the tumor, and surrounding its well-defined borders, were infiltrates of mature lymphocytes and plasma cells. Russell bodies were prominent in the latter. Adjacent brain tissue showed reactive changes with gliosis and numerous Rosenthal fibers. Immunohistochemically, tumor cells were strongly reactive for GFAP and vimentin, but negative or only weakly staining for EMA. The MIB-1 labeling index was approximately 1%. Ultrastructural examination of 4 cases revealed focal microvilli, scattered "intermediate" junctions, and focal basal lamina formation. Neither desmosomes nor cilia were seen. Total resections were achieved in 2 cases; only subtotal removals were achieved in 6. Subsequent tumor enlargement was noted in 3 of the 6 patients with incomplete resection, and of these, two died at post-operative intervals of 8 months and 3 years. The other patient survives 4 years post-operatively with stable residual disease. Of the 2 patients with total resection, 1 was lost to follow-up; the other, during a brief follow-up period, did well without evidence of recurrence.

Cleidocranial dysplasia with neonatal death due to central nervous system injury in utero: case report and literature review.

Cleidocranial dysplasia (CCD), an uncommon disorder involving membranous bones, is rarely lethal in early life. The calvaria is defective and wormian bones are present. Abnormalities of the clavicles vary in severity from a minor unilateral defect to bilateral absence. This report concerns pre- and postmortem anatomical and radiological findings in a 15-day-old female neonate with CCD. Her postnatal course was characterized by seizures and recognition of hydrocephalus during the first day of life. The calvaria was hypoplastic with numerous wormian bones. A pseudofracture of the right clavicle was present. Hydrocephalus was present in the brachycephalic brain which had a severely thinned cerebral cortex. Hemosiderin in the ventricular lining and marked subependymal gliosis were interpreted as evidence of old intraventricular hemorrhage that had occurred in utero. A CCD-related condition, Yunis-Varon syndrome (YVS), is noted for early lethality and for developmental and secondary abnormalities of the central nervous system. The present case only partially matches the phenotype of YVS and might represent a part of a spectrum of phenotypic variants ranging from viable CCD to lethal YVS.

Early pregnancy diagnosis in alpaca (Lama pacos) and llama (Lama glama) by ultrasound.

An ultrasonography study of early pregnancy diagnosis was carried out in 19 alpacas and 12 llamas, after controlled matings. The aim was to determine the earliest gestational age at which pregnancy diagnosis by transrectal ultrasonography could be achieved, and to generate an empirical formula for gestational sac diameter (GSD) growth as a function of gestational age (GA), allowing an estimate of GA during the first month of pregnancy. We found that pregnancy diagnosis may be carried out as early as 9 days after mating in alpacas and 7 days in llamas. This diagnosis was found to be accurate at 23 days in alpacas and 34 days in llamas. The empirical relations that best describe the relationship between GSD and GA were GA = logGSD + 1.2339/0.0585 r = 0.85; P < 0.001 in alpacas, and GA = logGSD + 1.2649/0.0546 r = 0.77, P < 0.001 in llamas, where GA is measured in days and GSD in centimeters. Our results also indicate that ultrasonography is a reliable technique for early pregnancy diagnosis. Furthermore, the empirical formulae reliably make it possible to estimate GA from GSD during the first month of pregnancy and their use might improve the efficiency of camelid breeders.

Brainstem tegmental necrosis and olivary hypoplasia: a lethal entity associated with congenital apnea.

Previously, we reported an isolated case of a newborn with central apnea at birth, ventilator-dependence, and combined malformative and destructive brainstem lesions (1). We now report 2 additional cases with similar clinicopathologic features. All 3 patients were male (XY karyotype) and required immediate ventilatory support in the delivery room. Perinatal complications included polyhydramnios and breech presentation. Variable cranial nerve palsies and orofacial and limb anomalies were present. The patients dies within minutes of withdrawal of ventilatory support at 2 to 11 weeks after birth. Significant neuropathologic findings were localized to the caudal pons and medulla, and included tegmental necrosis (neuronal loss, gliosis, mineralization) with involvement of respiratory-related nuclei, and anomalies of rhombic lip derivatives (olivary hypoplasia, arcuate nucleus hyperplasia). Three-dimensional computer reconstructions facilitated clinicoanatomic correlations, and underscored the restriction of the lesions to pontine and medullary rhombomeres and rhombic lip. The histopathology of these cases suggests a malformative process occurring at the end of the first trimester (time of rhombic lip migrations), and a superimposed destructive process (tegmental necrosis) in the second half of gestation. Although the etiology is unknown, the segmental nature of the lesions suggests the possibility of an abnormality in homeobox gene regulation. These cases likely represent a distinct clinicopathologic entity that should be considered in the differential diagnosis of Moebius syndrome and failure to breathe at birth.