PubMed Health⌕ Search

Biomedical subjects

D Reay

Publications and source records attributed to D Reay.

6 recordsLinked to original sources

Local high-capacity adenovirus-mediated mCTLA4Ig and mCD40Ig expression prolongs recombinant gene expression in skeletal muscle.

Multiple forms of muscular dystrophy are due to the absence of cytoskeletal muscle proteins that normally protect the integrity of muscle cells. The lack of any adequate treatments for these devastating diseases propels research toward the development of strategies for gene delivery to skeletal muscle. High-capacity adenoviral vectors (HC-AdV) devoid of all viral coding sequences have been developed to avoid expression of viral proteins by the gene therapy vector. However, the capsid proteins that are an essential component of the input viral vector and any residual helper virus in the vector preparation could induce an immune response. Furthermore, the therapeutic protein provided by a gene transfer vector presents the potential to induce an immune response in a patient who does not express a normal cellular protein due to genetic mutation. Therefore, we hypothesize that some immune suppression will be required with therapeutic gene delivery designed for the treatment of patients with inherited muscle diseases. In this study, we constructed and rescued three HC-AdVs expressing murine CTLA4Ig, murine CD40Ig, or both. The backbone vector without a gene insert was rescued as a negative control vector. The production of relevant proteins from each vector was determined in vitro. In vivo function of each of the immunosuppressant vectors was assayed by co-injection with an enhanced green fluorescent protein (EGFP)-expressing first-generation adenoviral vector (AdEGFP) into the tibialis anterior muscle of C57BL/10 mice. Higher levels of muscle EGFP expression were observed in animals receiving an immunosuppressant vector. Furthermore, the production of total anti-AdV and anti-EGFP antibodies was reduced in mice treated with each of the three immunosuppressant vectors. A second intramuscular administration of AdEGFP alone 4 weeks after the initial co-injection was successful in all immunosuppressant vector-treated groups, but not in the negative control vector-treated group. All groups had a high antibody response to adenoviral proteins after the second injection of AdEGFP alone, indicating that the initial co-injection did not tolerize against vector capsid antigens.

Abatacept↗

Postmortem perianal findings in children.

The postmortem finding of anal dilation or an exposed pectinate line in children who have died under suspicious circumstances continues to raise the concern of possible sexual abuse. The following multicenter, collaborative study was designed to help address that question. Sixty-five subjects, ranging in age from birth to 17 years, were autopsied at three different sites. A standard protocol along with 35-mm cameras were used to record the results. Thirty-eight (58%) subjects were boys, and 27 (42%) were girls. Forty-two (65%) were white, 10 (15%) African-American, five (8%) Asian, three (5%) white Hispanic and five (8%) other. Fifty-seven (88%) were in Tanner stage I of secondary sexual development. Thirty-four (52%) died of natural causes, 26 (40%) from accidental injuries, three (5%) from other causes, and four (6%) as a result of a homicide. Forty-eight subjects (74%) had some dilation of the anal sphincters. In 21 children (32%), the entire anal canal, including the rectal ampulla, could be visualized. In another 21 (32%) subjects, the pectinate line was exposed. Only the outer portion of the anal canal opened in six children (10%), whereas 17 (26%) had no dilatation of the anus. Anal laxity led to flattened skin folds in 50 (77%), a shallow anal canal in 40 (62%), the exposure of both the pectinate line in 38 (59%), and the anal mucosa in 24 (37%). Venous congestion was present in 14 (22%), venous pooling in three (5%), erythema in six (9%), and increased pigmentation in eight (12%). Funneling was found in two (3%). Blood was present in three (5%), and an abrasion was discovered in one (2%). No fissures, lacerations, hemorrhoids, or scars were found in any of the children. Anal orifice size varied with the age of the child, the amount of traction applied to the buttocks, and a history of a CNS injury at the time of death. It is suggested, finally, that anal dilatation alone cannot be used a marker for prior sexual abuse and the exposure of the pectinate line should not be confused with tears or fissures of the anal verge. Further studies of children known to have been sodomized prior to death are required.

Anal Canal↗

Validating survey responses to questions about gun ownership among owners of registered handguns.

While survey-based data on firearm ownership are essential for epidemiologic studies of the relation between gun ownership and injuries, the validity of respondent answers to questions about gun ownership has not been confirmed. In order to assess the accuracy of interview data about firearms, in June to August 1987, the authors attempted to contact residents of 75 homes in the cities of Memphis, Tennessee and Seattle, Washington listed as the address of the owner of a recently registered handgun. Despite problems with inaccurate registration data, contact was ultimately made with 55 households, 35 of which consented to a general interview that included a series of questions about gun ownership. Respondents in 31 of these 35 households (88.6%) readily acknowledged that one or more guns were kept in their home. Respondents in three of the remaining four households (8.6%) stated that guns were recently kept in their homes but were no longer kept there. Only one respondent (2.9%) denied categorically that guns of any kind were kept in her home. The authors conclude that, at least among registered gun owners, respondent answers to questions about gun ownership are generally valid and that survey data of this type can be utilized with confidence.

Adult↗

Nasogastric tube displacement in acute traumatic rupture of the thoracic aorta: a postmortem study.

Acute traumatic rupture of the thoracic aorta is an often fatal deceleration injury with only 15%--20% of victims surviving to receive emergency treatment. Numerous chest radiographic findings associated with this injury have been reported, but all are nonspecific. Nasogastric tube deviation to the right has been recently described in two series as a more sensitive and specific sign of aortic rupture, said to be present in 92.8% with rupture and in none with normal thoracic aortas. In this study of eight victims of fatal motor vehicle accidents with documented aortic rupture, five (62.5%) had nasogastric tube deviation to the right and three (37.5%) had deviation to the left. This supports other reported clinical experience suggesting that rightward nasogastric tube deviation in only 60%--70% sensitive for aortic rupture. Thus, absence of nasogastric tube deviation to the right does not exclude the diagnosis of aortic rupture, and decision-making regarding aortography must be based on other clinical and radiologic criteria.

Accidents, Traffic↗

The role of autopsy on patients with burns.

Burn center verification requires the use of autopsy as one method of quality assurance in a burn center. Because of the decreasing rates of autopsies worldwide and improved diagnostic accuracy in our critical care units, we tested the hypothesis that autopsy diagnosis would not alter our clinical diagnosis. A chart review of all deaths (N = 94) that occurred during a 6-year period (1989-1994) was performed. The clinical diagnoses from the hospital charts and autopsy reports for the patients were reviewed, and diagnostic discrepancies were classified as class I or class II errors. Class I diagnostic errors might have altered the clinical outcome. Class II errors were attributable to the burn injuries but were believed to have had little impact on the clinical outcome. The overall autopsy rate was 93.6% (n = 88). Clinical diagnostic errors were found in 16 (18%) of 88 patients. Five class I errors were found in 4 patients (4.5%), and 15 class II errors were found in 13 patients (14.7%). Although the rate of potentially serious errors was low (only 4.5% of the patients in this study) postmortem examinations revealed clinical diagnostic errors. The results of this study support the continued use of autopsies as a means of quality assurance, despite our ability to closely monitor our critically ill patients with burns.

Adolescent↗