Fraser syndrome without cryptophthalmos: Two cases.

Fraser syndrome (MIM#219000) is an autosomal recessive disorder, characterized by the association of cryptophthtalmos, syndactyly of the four extremities, urinary tract abnormalities and laryngo-tracheal anomalies. This condition is due to homozygous or compound heterozygous mutations in the FRAS/FREM complex genes: FRAS1, FREM2 and GRIP1. Here we report two atypical cases of Fraser syndrome due to mutations in the FRAS1 gene without cryptophthalmos. The first proband had syndactyly of three extremities, bilateral nostril coloboma, dysplastic ears with bilateral conductive hearing loss, blepharophimosis and lacrimal duct abnormalities. FRAS1 sequencing identified two pathogenic compound heterozygous variants: a nonsense variant in exon 70 and a missense variant in exon 24. The second proband had membranous syndactyly of the four extremities, left renal agenesis, laryngeal and ano-rectal malformations, dysplastic ears and bilateral conductive hearing loss. FRAS1 sequencing identified a pathogenic homozygous variant in the last exon of the gene. This first description of molecularly confirmed cases with Fraser syndrome without cryptophthalmos could contribute to further delineation of the clinical spectrum of Fraser syndrome, especially for possible phenotypically milder cases. Larger cohorts are required to try to refer the hypothesis of genotype-phenotype correlation.

A molecular basis of cryopreservation failure and its modulation to improve cell survival.

The requirement for more effective cryopreservation (CP) methodologies in support of the emerging fields of cell bioprocessing and cell therapy is now critical. Current CP strategies appropriately focus on minimizing the damaging actions of physicochemical stressors and membrane disruption associated with extra- and intracellular ice formation that occurs during the freeze-thaw process. CP protocols derived from this conceptual paradigm, however, yield suboptimal survival rates. We now provide the first report on the identification of delayed-onset cell death following CP and the significance of modulating molecular biological aspects of the cellular responses (apoptosis) to low temperature as an essential component to improve postthaw outcome. In this study we quantitatively examined the molecular basis of cell death associated with CP failure in a canine renal cell model. In addition, we report on the significant improvement in CP outcome through the modulation of these molecular mechanisms by the utilization of an organ preservation solution. HypoThermosol. Further, the utilization of HypoThermosol as the preservation medium and the modulation of molecular-based cell death have led to a paradigm shift in biologic preservation methodologies. The recognition of molecular mechanisms associated with CP-induced cell death offers the promise of improved CP of more complex and/or fragile biological systems such as stem cells, engineered tissues, and human organs.

Clearance rate of luteinizing hormone and follicle stimulating hormone from peripheral circulation in the pig.

Passive immunization of chronically ovariectomized gilts against gonadotropin releasing hormone (GnRH) resulted in an abrupt cessation of pulsatile secretion of luteinizing hormone (LH) accompanied by clearance from serum with a mean half-life of 30.9 +/- 2.3 (mean +/- SE) and 918 +/- 200 min for the first and second compartment, respectively. Serum follicle stimulating hormone (FSH) was unaffected immediately by passive immunization against GnRH and declined slowly with a half-life of 4.9 +/- .7 d. After LH and FSH had declined to basal levels in passively immunized gilts, injection of a bolus of LH and FSH resulted in peak values within 5 min and depletion curves with half-lives for the first compartment of 28.0 +/- 1.3 and 36.4 +/- 2.6 min and for the second compartment of 679 +/- 98 and 1,230 +/- 54 min, for LH and FSH respectively. These results show that the half-life of LH is similar following immunoneutralization of GnRH or administration of a bolus of LH in immunized gilts and a difference in clearance rates of LH and FSH after initial passive immunization. These results suggest that secretion of FSH in the ovariectomized gilt is controlled by factors in addition to hypothalamic GnRH.

Health care in the distended society: the American hospital in its social contexts.

The hospital at every stage in its development has been a product of social, political, cultural, and economic forces as well as a reflection of the kind of medical and scientific knowledge available in a given era. That we have as many hospitals as we do, that they are organized and financed the way are, that they practice the kind of medicine and provide the services they do (and that they now face the crises they do) is a result of past decisions in which health concerns sometimes played only a marginal role. Institutional inertia--the fact that institutions once set in motion cling tenaciously to life--means that a set of historical facts which have little to do with health care has saddled the United States with a hospital system that now distorts our health care expenditures and even affects how we think about disease and health.

Second-generation microstimulator.

The first-generation injectable microstimulator was glass encased with an external tantalum capacitor electrode. This second-generation device uses a hermetically sealed ceramic case with platinum electrodes. Zener diodes protect the electronics from defibrillation shocks and from electrostatic discharge. The capacitor is sealed inside the case so that it cannot be inadvertently damaged by surgical instruments. This microstimulator, referred to as BION, is the main component of a 255-channel wireless stimulating system. BION devices have been implanted in rats for periods of up to 5 months. Results show benign tissue reactions resulting in identical encapsulation around BION and controls. Stimulation threshold levels did not change significantly over time and ranged between 0.81 to 1.35 mA for all the animals at a 60 micros pulse width. All of the tests performed to date indicate that the BION is safe and effective for long-term human implant. We have elected to develop BION applications by seeking collaboration with the research community through our BION Technology Partnership.