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Biomedical subjects

D B Brown

Publications and source records attributed to D B Brown.

At least 19 recordsLinked to original sources
PubMed2001

Use of aortic cuffs to exclude iliac artery aneurysms during AneuRx stent-graft placement: initial experience.

PURPOSE: As many as 39% of patients who undergo aortic endografting for abdominal aortic aneurysm disease will have ectasia of the iliac arteries that will require intervention. Coil embolization of the internal iliac artery and extension of the graft to the external iliac artery is one solution to this problem. However, 19%-41% of these patients experience buttock claudication, which may be permanent, after unilateral embolization. The authors examined an alternative: the use of larger-sized aortic cuffs to seal the iliac limb. Outcomes and short-term results are presented in this article. MATERIALS AND METHODS: From October 1999 to August 2000, 144 AneuRx stent-grafts were placed at the authors' institution. Among the population receiving stent-grafts, 14 patients had 15 aortic cuffs placed across the distal iliac graft limbs to seal them and preserve flow to the internal iliac artery. One patient had bilateral cuffs placed. Five patients had embolization of the contralateral internal iliac artery because of bilateral disease. Patients were followed with computed tomography (CT) at 1, 6, and 12 months to evaluate for endoleaks. RESULTS: One- and 6-month endoleak rates, determined from only those patients with follow-up CT, were 0% and 10%, respectively. One type II endoleak was first discovered 9 months after graft placement. It sealed spontaneously at 15-month follow-up. One patient among the five who had internal iliac artery embolization had claudication. Mean CT follow-up was 7.8 months (range, 1-15). One patient declined CT but was alive and well 11 months after endografting. One patient moved across the country and declined follow-up. CONCLUSION: Placement of aortic cuffs in dilated iliac arteries can preserve flow to the ipsilateral internal iliac artery and provide an adequate seal. Additionally, the option of later treatment is maintained. Patients with bilateral iliac ectasia can undergo stent-graft placement without bilateral internal iliac artery embolization. Longer-term follow-up in larger numbers of patients will be important to determine the ultimate durability of this technique.

Aortic Aneurysm, Abdominal↗
PubMed2001

The nitroxide Tempol affords protection against ultraviolet radiation in a transgenic murine fibroblast culture model of cutaneous photoaging.

The generation of reactive oxygen species is among the various mechanisms by which ultraviolet radiation damages skin. Tempol, a superoxide dismutase analogue which readily penetrates cell membranes when administered exogenously, has been shown to provide protection against some forms of oxygen-dependent damage. In this study, we measured the ability of Tempol to protect against ultraviolet A- and ultraviolet B-induced damage, using a previously described transgenic mouse model of cutaneous photoaging. The ability of Tempol to prevent ultraviolet radiation-induced elastin promoter activation was determined in vitro. Tempol provided over 50% protection against ultraviolet B and over 70% protection against ultraviolet A as measured in our in vitro system. These results demonstrate the ability of the superoxide dismutase mimic, Tempol, to protect against ultraviolet induced elastin promoter activation. This compound could be a useful pharmacological agent to prevent cutaneous photoaging.

Animals↗
PubMed2001

Ultraviolet-filtering properties of commonly used tissue cell culture plasticware.

BACKGROUND: Fluorescent sunlamps are a common source of ultraviolet radiation (UVR) for photobiology research. However, these lamps emit a significant amount of biologically "irrelevant" wavelengths that, if not removed, can drastically skew results and perhaps lead to mistaken conclusions regarding human photobiology. The use of a cellulose triacetate sheet (Kodacel) to filter the shorter ultraviolet wavelengths has become the accepted standard in photobiology. Over time, the transmission characteristics of this sheet may be altered due to photochemical changes. In addition, in vitro experiments utilizing filtered fluorescent sunlamps require the removal of plastic tissue cell culture lids, increasing the possibility of contamination. METHODS: We evaluated the transmission characteristics of various commercially available plastic lids used in tissue cell cultures. In addition, we used a biological system containing the human elastin promoter/chloramphenicol acetyltransferase reporter gene construct to compare the effects of filtering from these plastic lids. RESULTS: Here, we demonstrate that the transmission of UVR and the biological response through plastic culture dish lids is similar to that of Kodacel. CONCLUSION: Although this is an improvement for in vitro experiments, further improvements can be made using more realistic UVR sources, e.g. UVA-340 lamps, which mimic the short wavelengths of sunlight.

Animals↗
PubMed2001

Glycolic acid treatment increases type I collagen mRNA and hyaluronic acid content of human skin.

BACKGROUND: Chronic solar irradiation results in both morphologic and functional changes in affected skin. alpha-hydroxy acids, such as glycolic acid, have been shown to improve photodamaged skin. OBJECTIVE: To investigate alterations in collagen gene induction and epidermal and dermal hyaluronic acid production as a result of administered glycolic acid. METHODS: In this study we compared collagen gene expression from skin biopsy specimens, and epidermal and dermal hyaluronic acid immunohistochemical staining between glycolic acid-treated and vehicle-treated skin. Forearm skin was treated with 20% glycolic acid lotion or a lotion vehicle control twice a day for 3 months. RESULTS: Epidermal and dermal hyaluronic acid and collagen gene expression were all increased in glycolic acid-treated skin as compared to vehicle-treated controls. CONCLUSION: Our data suggest that epidermal and dermal remodeling of the extracellular matrix results from glycolic acid treatment. Longer treatment intervals may result in collagen deposition as suggested by the measured increase in mRNA.

Aged↗
PubMed2000

Diminished decondensation and DNA synthesis in activated sperm from rats treated with cyclophosphamide.

Standard andrology tests do not predict fertility or assess the genetic quality of spermatozoa. To address these problems, we have analyzed sperm nuclear activation in vitro using cytoplasmic extracts of Xenopus laevis frog eggs. The objective of this study was to determine if rat sperm chemically damaged in vivo by cyclophosphamide treatment would respond abnormally in an in vitro rat sperm activation assay (RSAA). Male Sprague-Dawley rats were treated for 6 weeks with cyclophosphamide (CP) to induce DNA damage in post-meiotic germ cells. After the treatment period, cauda epididymal sperm were isolated, and incubated in cytoplasmic extracts of X. laevis frog eggs to induce chromatin decondensation and DNA synthesis in vitro. Sperm from treated rats displayed significant decreases in both decondensation and DNA synthesis when compared to sperm from control rats, consistent with the presence of CP-induced DNA crosslinks. No differences in body, testes, or epididymal weights were observed between control and treated rats, nor was sperm count diminished in the treatment group. These results demonstrate that the RSAA can be used to detect damaged sperm chromatin in the absence of detrimental effects on sperm count, and testis and epididymal weights.

Animals↗
PubMed2000

Glass needle-mediated microinjection of macromolecules and transgenes into primary human blood stem/progenitor cells.

A novel glass needle-mediated microinjection method for delivery of macromolecules, including proteins and larger transgene DNAs, into the nuclei of blood stem/progenitor cells was developed. Temporary immobilization of cells to extracellular matrix-coated dishes has enabled rapid and consistent injection of macromolecules into nuclei of CD34(+), CD34(+)/CD38(-), and CD34(+)/CD38(-)/Thy-1(lo) human cord blood cells. Immobilization and detachment protocols were identified, which had no adverse effect on cell survival, progenitor cell function (colony forming ability), or stem cell function (NOD/SCID reconstituting ability). Delivery of fluorescent dextrans to stem/progenitor cells was achieved with 52% +/- 8.4% of CD34(+) cells and 42% +/- 14% of CD34(+)/CD38(-)cells still fluorescent 48 hours after injection. Single-cell transfer and culture of injected cells has demonstrated long-term survival and proliferation of CD34(+) and CD34(+)/CD38(-) cells, and retention of the ability of CD34(+)/CD38(-) cells to generate progenitor cells. Delivery of DNA constructs (currently </= 19.6 kb) and fluorescently labeled proteins into CD34(+) and CD34(+)/CD38(-) cells was achieved with transient expression of green fluorescent protein observed in up to 75% of injected cells. These data indicate that glass needle-mediated delivery of macromolecules into primitive hematopoietic cells is a valuable method for studies of stem cell biology and a promising method for human blood stem cell gene therapy. (Blood. 2000;95:437-444)

ADP-ribosyl Cyclase↗
PubMed2000

Angioscopic observations after percutaneous thrombectomy of thrombosed hemodialysis grafts.

PURPOSE: To use angioscopy to evaluate and compare the amount of residual thrombus and endoluminal wall damage in hemodialysis grafts after percutaneous thrombectomy procedures. MATERIALS AND METHODS: Thirty-nine thrombectomy and angioscopy procedures were performed in 35 patients. Percutaneous thrombectomy methods included eight different mechanical thrombectomy devices and the "lyse and wait" technique. Videotaped images of 33 angioscopic examinations were independently reviewed by three radiologists. Two parameters-the amount of residual thrombus and degree of endoluminal wall damage-were scored on a scale of 1 to 5. Data were initially analyzed to validate the grading system and then further studied to compare the different thrombectomy techniques. RESULTS: The Spearman rank order analysis validated the data pertaining to the amount of residual thrombus (r = 0.71, P < .0001), but there was poor correlation between reviewers regarding the degree of endoluminal wall damage. Combined scores from three reviewers revealed that the Cragg brush and Percutaneous Thrombectomy Device (PTD) left the smallest amounts of residual thrombus. The other methods tested, listed by increasing amount of residual thrombus, were the Endovac, Hydrolyser, Amplatz Thrombectomy Device, AngioJet, Oasis, and the lyse and wait technique. There were two complications related to angioscopy procedures. CONCLUSION: Subjective observations reveal that wall-contact thrombectomy devices leave less residual thrombus than hydrodynamic devices, aspiration devices, or the lyse and wait technique.

Angioscopy↗
PubMed2000

Creation of radiopaque thrombi for in vivo experiments.

PURPOSE: A number of percutaneous thrombectomy devices are undergoing investigation for treatment of patients with venous thromboembolism. Use of radiopaque thrombus to monitor thrombus delivery and assess thrombectomy has been previously reported. The purpose of this project was to quantitatively test the effect of mixing different ratios of blood and contrast material to facilitate maximum thrombus formation and radiopacity. MATERIALS AND METHODS: The following ratios of blood and contrast material were mixed: 2 mL blood to 8 mL contrast material (ratio = 0.25), 4 mL blood to 6 mL contrast material (ratio = 0.67), 6 mL blood to 4 mL contrast material (ratio = 1.5), and 8 mL blood to 2 mL contrast material (ratio = 4). Contrast material was added at day 0, 3, or 6. Each sample received one of two ionic contrast agents to opacify the clots. At day 14, thrombus mass and opacity were determined. RESULTS: Three combinations of blood and contrast material produced maximum thrombus and radiopacity. These were sodium iothalamate 30% with a ratio of 4 with contrast material added on day 0 and sodium iothalamate 60% with a ratio of 1.5 with contrast material added on day 3 or 6. CONCLUSIONS: When forming radiopaque thrombi, significant differences can result from the ratio of blood to contrast material used. Contrast material type can also affect radiopacity and mass formed. The use of optimal ratios of blood to contrast material should maximize device evaluation with minimal wasting of valuable resources such as test subjects, physician time, and equipment.

Contrast Media↗
PubMed2000

Common fluorescent sunlamps are an inappropriate substitute for sunlight.

Fluorescent sunlamps are commonly employed as convenient sources in photobiology experiments. The ability of Kodacel to filter photobiologically irrelevant UVC wavelengths has been described. Yet there still remains a major unaddressed issue--the over representation of UVB in the output. The shortest terrestrial solar wavelengths reaching the surface are approximately 295 nm with the 295-320 nm range comprising approximately 4% of the solar UV irradiance. In Kodacel-filtered sunlamps, 47% of the UV output falls in this range. Consequently, in studies designed to understand skin photobiology after solar exposure, the use of these unfiltered sunlamps may result in misleading, or even incorrect conclusions. To demonstrate the importance of using an accurate representation of the UV portion of sunlight, the ability of different ultraviolet radiation (UVR) sources to induce the expression of a reporter gene was assayed. Unfiltered fluorescent sunlamps (FS lamps) induce optimal chloramphenicol acetyltransferase (CAT) activity at apparently low doses (10-20 J/cm2). Filtering the FS lamps with Kodacel raised the delivered dose for optimal CAT activity to 50-60 mJ/cm2. With the more solar-like UVA-340 lamps somewhat lower levels of CAT activities were induced even though the apparent delivered doses were significantly greater than for either the FS or Kodacel-filtered sunlamp (KFS lamps). When DNA from parallel-treated cells was analyzed for photoproduct formation by a radioimmuneassay, it was shown that the induction of CAT activity correlated with the level of induced photoproduct formation regardless of the source employed.

Animals↗
PubMed2000

Micro-injection-mediated hematopoietic stem cell gene therapy.

Over the past decade, significant attention has been devoted to the development of viral vectors (i.e., retrovirus, lentivirus, adeno-associated virus) and conditions capable of transducing hematopoietic stem cells. After several years of disappointing results, recent reports in humans and other primates, most particularly the French report of successful treatment of X-linked severe combined immune deficiency (SCID) [1.], indicate that viral approaches will be successful in treating specific hematopoietic diseases. However, it is clear that alternate non-viral methods of gene delivery and genetic modification offer significant advantages, and may in fact be the only effective approach for treating certain blood diseases. In this review, we focus on glass needle-mediated micro-injection as a method for the delivery of genetic material into blood stem cells, with an emphasis on molecules capable of either compensating gene deletions/mutations or directly repairing gene mutations.

Animals↗
PubMed1999

Characteristics of traffic crashes among young, middle-aged, and older drivers.

An overview of the characteristics of traffic crashes among young, middle-aged and older drivers is presented. The results suggest that the youngest and the oldest drivers were more likely to be considered at-fault. With respect to crash characteristics, older drivers were less likely to have crashes involving driver fatigue, during the evening and early morning, on curved roads, during adverse weather, involving a single vehicle, and while traveling at high speeds. Conversely, older drivers were over-represented in crashes at intersections and/or involving failure to yield the right of way, unseen objects, and failure to heed stop signs or signals. Crashes occurring while turning and changing lanes were also more common among older drivers. Alcohol was less likely to be a factor in traffic crashes involving older adults. Synthesizing these results led to the conclusion that the primary problem with the young is risk-taking and lack of skill. The strength of older drivers lies in their aversion to risk, but perceptual problems and difficulty judging and responding to traffic flow often counterbalance this attribute.

Accidents, Traffic↗
PubMed1999

Evaluation of the efficacy of 2- versus 3-dimensional computed tomography.

Simulated 3-dimensional (3-D) representation of computerized data is a valuable diagnostic tool in evaluation of tumors of the central nervous system. Several reports exist regarding the clinical value of 3-D imaging, but there is little objective evidence to quantify improved performance from the images. The purpose of this study was to quantify the efficacy of simulated 3-D versus 2-D image interpretation in a nonclinical model. A 3-tiered, 3-D model was constructed, and objects were placed in varied positions. CT was then performed on each of the models. Fifty-three subjects were shown the CT images and asked to reconstruct the model as depicted by either 2-D or simulated 3-D images. Performance between subject groups was different depending on clinical experience. In addition, it was found that the 3-D representation of data allowed for a significantly faster performance of the task of image interpretation and reconstruction of the model.

Clinical Competence↗
PubMed1999

Evaluation of a modified arrow-trerotola percutaneous thrombolytic device for treatment of acute pulmonary embolus in a canine model.

PURPOSE: Massive pulmonary embolus (PE) is often rapidly fatal. Surgical thrombectomy has a mortality rate as high as 74%. Multiple percutaneous methods have been tested with limited success. The purpose of this study was to evaluate the Arrow-Trerotola percutaneous thrombolytic device (PTD) for (i) the ability to clear pulmonary embolus and (ii) the effect on normal pulmonary vasculature. These were tested in a canine model. MATERIALS AND METHODS: Iatrogenic unilateral massive PEs were created in nine canines. These PEs were then treated with the PTD. The device was also activated in the normal pulmonary artery. Immediately after treatment, six animals were killed. Three animals were allowed to recover and underwent pulmonary arteriography 1 month later to evaluate pulmonary hypertension, stenosis, or occlusion; they were then killed. Autopsy specimens were evaluated for histologic evidence of acute or chronic vascular injury. RESULTS: Acutely, the PTD effectively thrombolysed the PE in all animals. Histologically, there was moderate intimal injury, but no evidence of pulmonary artery disruption. There was one device failure. One month after treatment, there was no radiographic evidence of pulmonary stenosis at device activation sites, no pulmonary hypertension, and only mild histologic evidence of scar formation. CONCLUSION: In preliminary animal testing, the PTD is safe and effective for treating large central pulmonary emboli. Human clinical trials are warranted.

Angiography↗
PubMed1999

Determination of inferior vena cava diameter in the angiography suite: comparison of three common methods.

PURPOSE: Significant inferior vena cava (IVC) filter migration has been associated with deployment of some filter types in IVCs measuring more than 28 mm in diameter at inferior vena cavography. The purposes of this study were to (a) determine if significant differences exist between IVC measurements obtained using a gold standard technique and two other widely accepted methods, and (b) if differences exist, how often do these differences cause incorrect IVC sizing around a diameter of 28 mm, with its associated filter migration issues. MATERIALS AND METHODS: One hundred thirteen consecutive inferior vena cavograms were retrospectively reviewed. The transverse diameter of the infrarenal IVC was determined by using a calibrated intravascular catheter (the gold standard), subtraction of 20% from the measured transverse IVC diameter on a cut-film radiograph, and a radiopaque ruler placed immediately posterior to the patient. RESULTS: The concordance correlation of the 20% magnification method versus internal calibration was 0.94. Kappa analysis to determine agreement at a diameter of 28 mm yielded a Kappa coefficient of 0.490. The concordance correlation of an external ruler versus internal calibration was 0.43, with a Kappa coefficient of 0. CONCLUSION: The poor Kappa correlations for both methods demonstrate that they are unreliable in identifying megacava. Inferior vena cavography prior to IVC filter placement should be performed with a calibrated intravascular catheter.

Angiography↗
PubMed1999

Treatment of spider veins using a 10 millisecond pulse-duration frequency-doubled neodymium YAG laser.

BACKGROUND: The pulsed dye laser has been the standard for treating vascular lesions. Although quite effective for treating facial vessels and port-wine stains, spider veins of the lower extremities are more difficult to treat. Recent studies have shown that lasers with longer pulse durations are more effective at treating spider veins. A new long-pulse frequency-doubled Neodymium:YAG laser has been developed with a 10-ms pulse duration and sufficient energy to enable treatment with a 3- or 4-mm diameter treatment beam. OBJECTIVE: To determine the effectiveness of the long pulse Neodymium:YAG laser for treating spider veins of the lower extremities. METHODS: Spider veins less than 0.75 mm in diameter on the legs of 15 female volunteers were treated in 1 or 2 areas. Treatments were administered through a water-cooled chill tip using the frequency-doubled Neodymium:YAG laser with a 10-ms pulse duration. A dose of 16 J/cm2 was administered, completing 3 passes over each visible vein during each session, for a total of 2 sessions administered 6 weeks apart. Photographs of treatment areas were digitally analyzed for degree of vessel clearance. RESULTS: Computer-based image analysis revealed clearing of over 75% of veins following 2 treatments with 16 J/cm2. Side effects were minimal, and the treatments were well tolerated. CONCLUSIONS: The 532 nm, 10 ms pulse duration, frequency-doubled Neodymium:YAG laser is safe and effective for treating spider veins of the lower extremities less than 0.75 mm in diameter, in patients with Fitzpatrick skin Types I-III.

Adult↗
PubMed1999

Residual thermal damage resulting from pulsed and scanned resurfacing lasers.

BACKGROUND: Laser resurfacing with rapidly scanned or pulsed carbon dioxide (CO2) lasers has evolved rapidly in recent years. These lasers vaporize small amounts of tissue, while leaving minimal residual thermal damage. OBJECTIVE: To compare the depth of residual thermal damage of two of the most commonly used CO2 laser systems. A rapidly scanned laser was compared to a short-pulse laser system. METHODS: Laser treatment was performed on abdominoplasty specimens prior to removal in four subjects. One, two, or three passes of the two most commonly used energies were administered using each laser system. RESULTS: The depth of thermal damage increased with a greater number of passes with each laser system. Higher energies resulted in greater residual thermal damage with each system after the first pass up to three passes, which was the maximum number of passes administered. Combining the second and third passes, residual thermal damage was remarkably similar when comparing the pulsed and scanned lasers. CONCLUSIONS: The most commonly used energy settings of two lasers with very different modes of action resulted in remarkably similar depths of thermal damage, suggesting that the zone of thermal damage may correlate with clinical outcome. In addition, the zone of thermal damage enlarges as the number of passes increases from one to three.

Adult↗
PubMed1998

Altered nuclear activation parameters of rat sperm treated in vitro with chromatin-damaging agents.

Standard semen measures do not assess the genetic integrity of sperm. A human sperm activation assay (HSAA) has proven very useful for assessing sperm quality and predicting pregnancy outcome. The HSAA involves incubating permeabilized sperm in cytoplasmic extracts of Xenopus laevis frog eggs. The extracts activate sperm nuclei, which undergo chromatin decondensation, DNA synthesis, and chromatin recondensation, mimicking events that occur after fertilization in vivo. However, no animal model sperm activation assay has been reported. We hypothesize that sperm activation assays will be useful for studying molecular mechanisms of sperm DNA repair by egg cytoplasm and for screening sperm for damaged DNA. Thus, the objectives of this study were to develop an in vitro rat sperm activation assay (RSAA) using cytoplasmic extracts of X. laevis frog eggs and to determine how chemically damaging the sperm chromatin would affect two sperm activation parameters, chromatin decondensation and DNA synthesis. We incubated demembranated rat sperm in a cytoplasmic extract of X. laevis frog eggs supplemented with tritiated thymidine triphosphate ([3H]TTP). The activated sperm nuclei underwent chromatin decondensation and DNA synthesis. Decondensation kinetics were examined using image analysis to measure the size of the sperm nuclei as they decondensed. DNA synthesis kinetics were examined using autoradiography of incorporated [3H]TTP. To investigate how chemical damage affects nuclear activation, we treated rat sperm in vitro with ethylene glycolbis(sulfosuccinimidyl-succinate; SEGS), a reversible crosslinking agent, or hydroxylamine (HA), a DNA base modifier. Treatment with SEGS blocked decondensation in a dose-dependent manner. In contrast, treatment with HA enhanced decondensation, induced gross chromatin abnormalities, and increased [3H]TTP incorporation into activated sperm nuclei, responses consistent with an attempt by the egg cytoplasm to repair DNA damage. These results suggest that the RSAA may be useful for detecting damaged sperm chromatin as a result of toxicant exposure.

Animals↗