Association of HLA class I and class II polymorphisms with age-related macular degeneration.

Purpose: To evaluate whether HLA genotypes are associated with age-related macular degeneration (AMD).

Methods: HLA class I-A, -B, and -Cw and class II DRB1 and DQB1 principal allele groups were genotyped in two stages: initially for principal allele groups in a cohort of 100 AMD cases and 92 control subjects, and then, in the next 100 cases and controls from the same cohort, for alleles or allele groups with P < 0.1 on initial typing.

Mkks-null mice have a phenotype resembling Bardet-Biedl syndrome.

McKusick-Kaufman syndrome (MKS) is an autosomal recessive disorder characterized by post-axial polydactyly, congenital heart defects and hydrometrocolpos, a congenital structural abnormality of female genitalia. Mutations in the MKKS gene have also been shown to cause some cases of Bardet-Biedl syndrome (BBS) which is characterized by obesity, pigmentary retinopathy, polydactyly, renal abnormalities and hypogenitalism with secondary features of hypertension and diabetes. Although there is overlap in clinical features between MKS and BBS, MKS patients are not obese and do not develop retinopathy or have learning disabilities.

Mortality benefit of transfer to level I versus level II trauma centers for head-injured patients.

Objective: To determine whether head-injured patients transferred to level I trauma centers have reduced mortality relative to transfers to level II trauma centers.

Data Source/study Setting: Retrospective cohort study of 542 patients with head injury who initially presented to 1 of 31 rural trauma centers in Oregon and Washington, and were transferred from the emergency department to 1 of 15 level I or level II trauma centers, between 1991 and 1994.

Study Design: A bivariate probit, instrumental variables model was used to estimate the effect of transfer to level I versus level II trauma centers on 30-day postdischarge mortality.

Hypercoagulability is most prevalent early after injury and in female patients.

Background: Hypercoagulability after injury is a major source of morbidity and mortality. Recent studies indicate that there is a gender-specific risk in trauma patients. This study was performed to determine the course of coagulation after injury and to determine whether there is a gender difference.

The incidence and burden of ladder, structure, and scaffolding falls.

Objectives: The national morbidity and mortality associated with falls from a height is incompletely described. The authors estimated the rates of injury, hospitalization, and mortality due to these falls for subgroups of the U.S.

Encouraging the consumption of fruit and vegetables by older Australians: an experiential study.

Objective: To explore perceptions of dietary recommendations for fruit and vegetables, and barriers and opportunities for increasing consumption.

Design: Qualitative study with an experiential component.

Setting: Older adults' households.

Drosophila Spire is an actin nucleation factor.

The actin cytoskeleton is essential for many cellular functions including shape determination, intracellular transport and locomotion. Previous work has identified two factors--the Arp2/3 complex and the formin family of proteins--that nucleate new actin filaments via different mechanisms. Here we show that the Drosophila protein Spire represents a third class of actin nucleation factor.

Decreased thickness and integrity of the macular elastic layer of Bruch's membrane correspond to the distribution of lesions associated with age-related macular degeneration.

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. In its severest form, choroidal neovessels breach the macular Bruch's membrane, an extracellular matrix compartment comprised of elastin and collagen laminae, and grow into the retina. We sought to determine whether structural properties of the elastic lamina (EL) correspond to the region of the macula that is predilected toward degeneration in AMD.

Hospital factors associated with splenectomy for splenic injury: a national perspective.

Background: The management of patients with splenic injury has shifted from routine splenectomy to attempts at splenic salvage. Using the Healthcare Cost and Utilization Project's National Inpatient Sample (HCUP-NIS), we assessed the patterns of care for splenic trauma. We hypothesized that the processes of care in urban and rural hospitals would differ.

ASCIA guidelines for prevention of food anaphylactic reactions in schools, preschools and child-care centres.

These guidelines have been developed by the anaphylaxis working party of the Australasian Society of Clinical Immunology and Allergy to provide advice for minimizing the risk of food-induced anaphylaxis in schools, preschools and child-care centres. The guidelines outline four steps for the prevention of food anaphylactic reactions in children at risk and food policy measures specific to school age and preschool age children.

Bbs2-null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin.

Bardet-Biedl syndrome (BBS) is a heterogeneous, pleiotropic human disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, hypogenitalism, and an increased incidence of diabetes and hypertension. No information is available regarding the specific function of BBS2. We show that mice lacking Bbs2 gene expression have major components of the human phenotype, including obesity and retinopathy.

Results from screening over 9000 mutation-bearing mice for defects in the electroretinogram and appearance of the fundus.

Random mutagenesis combined with phenotypic screening using carefully crafted functional tests has successfully led to the discovery of genes that are essential for a number of functions. This approach does not require prior knowledge of the identity of the genes that are involved and is a way to ascribe function to the nearly 6000 genes for which knowledge of the DNA sequence has been inadequate to determine the function of the gene product. In an effort to identify genes involved in the visual system via this approach, we have tested over 9000 first and third generation offspring of mice treated with the mutagen N-ethyl-N-nitrosourea (ENU) for visual defects, as evidenced by abnormalities in the electroretinogram and appearance of the fundus.

Dynamic instability in a DNA-segregating prokaryotic actin homolog.

Dynamic instability-the switching of a two-state polymer between phases of steady elongation and rapid shortening-is essential to the cellular function of eukaryotic microtubules, especially during chromosome segregation. Since the discovery of dynamic instability 20 years ago, no other biological polymer has been found to exhibit this behavior. Using total internal reflection fluorescence microscopy and fluorescence resonance energy transfer, we observe that the prokaryotic actin homolog ParM, whose assembly is required for the segregation of large, low-copy number plasmids, displays both dynamic instability and symmetrical, bidirectional polymerization.

Advanced statistics: the propensity score--a method for estimating treatment effect in observational research.

Observational studies assessing the effect of a particular treatment or exposure may be subject to bias, which can be difficult to eliminate using standard analytic techniques. Multivariable models are commonly used in observational research to assess the relationship between a certain exposure or treatment and an outcome, while adjusting for important variables necessary to ensure comparability between the groups. Large differences in the observed covariates between two study groups may exist in observational studies in which the investigator has no control over who was allocated to each treatment group, and these differences may lead to biased estimates of treatment effect.

Asymmetric conjugate addition for the preparation of syn-1,3-dimethyl arrays: synthesis and structure elucidation of capensifuranone.

The synthesis of capensifuranone (1) has been achieved by the application of developments for asymmetric conjugate addition reactions of organocopper reagents with nonracemic N-enoyl-4-phenyl-1,3-oxazolidinones for the preparation of 1,3-syn-dimethyl arrays. The assignment of relative and absolute stereochemistry of 1 has been made following the high-field NMR characterizations of synthetic diol derivatives. The previously unassigned C4 stereochemistry of 1 was determined to be of the (S)-configuration.

Enterocutaneous fistula and ventral hernia after absorbable mesh prosthesis closure for trauma: the plain truth.

Hypothesis: The severity of abdominal injury is the determining factor for the development of enterocutaneous fistula and ventral hernia after absorbable mesh prosthesis closure (AMPC) for trauma.

Methods: We conducted a retrospective analysis of case series that included 140 consecutive trauma patients with AMPC surviving more than 48 hours from October 1, 1989, to March 31, 2000, at a Level I trauma center. The days until abdominal wall reconstruction was used as a measure of exposure of the viscera to the mesh.

Blunt carotid artery injury: the futility of aggressive screening and diagnosis.

Background: Blunt carotid artery injury (BCI) remains a rare but potentially lethal condition. Recent studies recommend that aggressive screening based on broad criteria (hyperextension-hyperflexion mechanism of injury, basilar skull fracture, cervical spine injury, midface fracture, mandibular fracture, diffuse axonal brain injury, and neck seat-belt sign) increases the rate of diagnosis of BCI by 9-fold. If this recommendation becomes a standard of care, it will require a major consumption of resources and may give rise to liability claims.

Bardet-Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly.

The functions of the proteins encoded by the Bardet-Biedl syndrome (BBS) genes are unknown. Mutations in these genes lead to the pleiotropic human disorder BBS, which is characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism. Secondary features include diabetes mellitus and hypertension.

Comparison of color to fluorescein angiographic images from patients with early-adult onset grouped drusen suggests drusen substructure.

Purpose: Recent structural and histochemical data from our laboratory indicate that human drusen often possess distinct, structural core domains. A similar, corelike structure is frequently noted clinically in some drusen-related conditions. To assess the nature of the corelike structures observed clinically, we evaluated color photographs and fluorescein angiograms from patients with early-adult onset grouped drusen (EAOGD).

Activation of Arp2/3 complex: addition of the first subunit of the new filament by a WASP protein triggers rapid ATP hydrolysis on Arp2.

In response to activation by WASP-family proteins, the Arp2/3 complex nucleates new actin filaments from the sides of preexisting filaments. The Arp2/3-activating (VCA) region of WASP-family proteins binds both the Arp2/3 complex and an actin monomer and the Arp2 and Arp3 subunits of the Arp2/3 complex bind ATP. We show that Arp2 hydrolyzes ATP rapidly-with no detectable lag-upon nucleation of a new actin filament.

Variations in injury patterns, treatment, and outcome for spinal fracture and paralysis in adult versus geriatric patients.

Study Design: Retrospective cohort analysis of hospital discharge and mortality data for spinal fracture and spinal cord injury patients in a single state from 1990 to 1995.

Objectives: Population-based review of preinjury patient factors, injury and treatment patterns, and in-hospital versus 60-day mortality in adult and geriatric spinal injury patients.

Summary Of Background Data: While population-based analyses of hospitalized injured patients indicate that geriatric patients are at higher risk for adverse outcome, less is known about the specific subset of patients with spinal fracture and spinal cord injury.

Crush injury and rhabdomyolysis.

Crush injuries resulting in traumatic rhabdomyolysis are an important cause of acute renal failure. Ischemia reperfusion is the main mechanism of muscle injury. Intravascular volume depletion and renal hypoperfusion, combined with myoglobinuria, result in renal dysfunction.

Adeno-associated virus type 5: transduction efficiency and cell-type specificity in the primate retina.

Gene transfer using adeno-associated viruses (AAVs) has been effective for treating inherited retinal diseases in animal models. Further evaluation in primates must be performed prior to clinical application, however, because of the difference between the retina of the primate and those of other animals. Prior work has shown that AAV2 can transduce rod-photoreceptor and RPE cells in the non-human primate retina and that AAV5 is more efficient at transducing photoreceptor cells than AAV2 in the rodent retina.