Biomedical subjects

S D Safford

Publications and source records attributed to S D Safford.

8 recordsLinked to original sources

PubMed2005

Longitudinal mechanical tension induces growth in the small bowel of juvenile rats.

INTRODUCTION: The aim of our study was to apply longitudinal force to the small bowel to increase the length of intestine in juvenile rats. METHODS: Fifty juvenile rats had double barrelled, blind loop ostomies created using an isolated segment of bowel. Our intestinal lengthening device was inserted into one of the loops and the second loop served as a control. Once the device was deployed, the experimental, control, and in situ segments of bowel were evaluated for length, weight, histology, and disaccharidase enzyme activity. RESULTS: Mechanical tension increased intestinal length by 149%. The lengthened bowel also exhibited a greater total weight (218%), greater mucosal weight (122%), and increased protein mass (164%) compared with the control limb of bowel. Histologically, there was a markedly increased thickness of the muscularis propria in the lengthened bowel (200% increase compared with the control limb). Functionally, we found increased total disaccharidase activity in the lengthened bowel (between 47% and 350%, depending on the particular enzyme tested; p<0.01). CONCLUSION: Mechanical tension induces intestinal growth by increasing length, weight of the bowel and mucosa, and protein mass. Histological changes, such as increases in Paneth cells, suggest that increased proliferation and reorganisation of the mucosa and muscularis propria are a response to mechanical tension. Functionally, increased intestinal length corresponds with increased disaccharidase activity, thus implying potential increased absorptive capacity of the lengthened bowel.

Animals↗

PubMed2004

Characterization of neuronal/glial differentiation of murine adipose-derived adult stromal cells.

Neural tissue has limited capacity for intrinsic repair after injury, and the identification of alternate sources of neuronal stem cells has broad clinical potential. Preliminary studies have demonstrated that adipose-derived adult stromal (ADAS) cells are capable of differentiating into mesenchymal and non-mesenchymal cells in vitro, including cells with select characteristics of neuronal/glial tissue. In this study, we extended these observations to test the hypothesis that murine (mu) ADAS cells can be induced to exhibit characteristics of neuronal and glial tissue by exposure to a cocktail of induction agents. We characterized the differentiation of muADAS cells in vitro using immunohistochemistry and immunoblotting, and examined whether these cells respond to the glutamate agonist N-methyl-D-aspartate (NMDA). We found that induced muADAS cells express proteins indicative of neuronal/glial cells, including nestin, GFAP, S-100, NeuN, MAP2, tau, and beta-III tubulin. Induced muADAS cells express gamma-aminobutyric acid (GABA), the NR-1 and NR-2 subunits of the glutamate receptor, GAP-43, synapsin I, and voltage-gated calcium channels. Finally, induced muADAS cells demonstrate decreased viability in response to NMDA. These findings suggest that muADAS cells can be induced to exhibit several phenotypic, morphologic, and excitotoxic characteristics consistent with developing neuronal and glial tissue.

Adipose Tissue↗

PubMed2001

Management of cholelithiasis in pediatric patients who undergo bone marrow transplantation.

PURPOSE: The aim of this study was to determine the incidence, risk factors, and proper management for asymptomatic cholelithiasis in children undergoing bone marrow transplantation (BMT). METHODS: The authors reviewed retrospectively the records of 575 children who underwent bone marrow transplantation at a University bone marrow transplantation unit (BMT) unit between February 1991 and October 1999. Of these patients, 235 underwent abdominal ultrasonography for evaluation of jaundice, sepsis, abdominal pain, or metastasis. To identify risk factors for cholelithiasis, the authors stratified the patients based on their disease and treatment regimen. Finally, the authors analyzed the natural history and management of BMT children with cholelithiasis. RESULTS: The authors identified 20 cases of cholelithiasis (8.5%) in the 235 BMT patients who underwent ultrasonography. Children who underwent BMT to treat bone marrow failure showed a significantly increased risk of cholelithiasis compared with children treated for malignancy (27% v 7.4%; P<.01). Most children (85%) with gallstones did not require surgical intervention. Specifically, 9 (45%) died from their primary disease, 5 (25%) showed sonographic resolution of their gallstones, and 3 (15%) underwent follow-up nonoperatively with persistent cholelithiasis. Three of the 20 patients with gallstones (15%) had signs of acute cholecystitis and underwent surgery. There were no surgical complications or deaths in the operative group. CONCLUSIONS: Cholelithiasis occurs at a high incidence in pediatric bone marrow transplant patients. Children undergoing BMT for bone marrow failure are at higher risk of having gallstones than those being treated for malignancy. Finally, these data support a strategy of nonoperative management for asymptomatic cholelithiasis in this highly selected group of patients.

Bone Marrow Transplantation↗

PubMed1998

Antisense basic fibroblast growth factor gene transfer reduces early intimal thickening in a rabbit femoral artery balloon injury model.

PURPOSE: The purpose of this study was to determine whether endogenous basic fibroblast growth factor (bFGF) production contributes to the intimal hyperplastic response to injury in a model of rabbit femoral artery balloon injury. Inhibition of de novo production of bFGF protein was targeted by intramural adenoviral gene transfer of antisense bFGF (Ad.ASbFGF) RNA. The adenovirus was delivered locally intraluminally at the time of arterial injury. METHODS: New Zealand White rabbits underwent balloon injury of the superficial femoral artery, followed by intraluminal delivery of an adenoviral vector encoding a rat antisense bFGF (ASbFGF) transcript at a concentration of 1 x 10(10) plaque-forming units per milliliter. Control animals were treated in a similar fashion, using either an adenovirus encoding the lac Z reporter gene (Ad.lacZ) or phosphate-buffered saline solution (PBS; vehicle) alone. Two weeks after balloon injury, rabbits were killed and perfusion fixed. Femoral arteries were harvested for histomorphometric analysis. Intimal and medial wall thickness was measured at eight points around the vessel perimeter, and mean intimal/medial (I/M) thickness ratios were compared by analysis of variance and Student's t test. In addition, medial cell proliferation in Ad.ASbFGF and Ad.lacZ treated arteries was evaluated 4 days and 2 weeks after balloon injury by 5-Bromo-2'-deoxyuridine labeling. RESULTS: At 14 days (n = 25) after balloon injury, histomorphometric analysis revealed a significant inhibition of intimal thickening in Ad.ASbFGF-treated arteries as compared with Ad.lacZ-treated and PBS-treated controls (I/M thickness ratios +/- SD, 0.43 +/- 0.22 for Ad.ASbFGF vs 1.03 +/- 0.28 for Ad.lacZ and 0.86 +/- 0.19 for PBS; p < 0.0001 and p = 0.004, respectively). There was no significant difference in the I/M thickness ratios of Ad.lacZ-treated and PBS-treated vessels (p = 0.27). Although there was no significant difference in the proliferation index of Ad.ASbFGF-treated and Ad.lacZ-treated vessels 4 days after injury, an increase in apoptosis was noted in the Ad.ASbFGF-treated vessels 4 days after balloon injury. CONCLUSIONS: The use of ASbFGF RNA gene transfer, designed to inhibit de novo bFGF synthesis after balloon injury, results in a significant inhibition of neointimal formation. This suggests that continued bFGF synthesis contributes to the arterial response to injury in rabbits. ASbFGF gene transfer may be an effective strategy in limiting the intimal hyperplastic response after vascular reconstructive procedures.

Adenoviridae↗

PubMed1998

Thermal preconditioning before rat arterial balloon injury: limitation of injury and sustained reduction of intimal thickening.

Heat shock proteins (HSPs) are a family of highly conserved proteins, essential to cell survival, that are induced during times of physiological stress. These proteins, when induced, can provide tolerance to subsequent injury. Several studies have documented that HSPs play an important role in the response of vascular cells to injury or stress. Whether the vasculature itself can be effectively preconditioned before arterial injury is unknown. Vascular HSP induction by whole-body hyperthermia (WBH) was evaluated with regard to its effects on the vascular response to balloon injury. WBH treatment of Sprague-Dawley rats (colonic temperatures of 41 to 42 degrees C for 15 minutes) resulted in maximal arterial HSP expression within 8 to 12 hours. Rats (male, 300 g, n=59) were randomly assigned to undergo either WBH or no treatment 8 hours before standard carotid balloon injury. At 14 (n=26) and 90 (n=21) days after balloon injury, histomorphometric analysis revealed a significant limitation of intimal accumulation in preconditioned arteries as compared to controls (intimal/medial area ratios+/-SEM: 14 days, 0.57+/-0.07 versus 0.86+/-0.08, P=0.01; 90 days, 0.78+/-0.12 versus 1.19+/-0.14, P<0.05). The medial cell proliferation index at 4 days (n=12) was significantly reduced in the treated group as well (3.6+/-0.9% versus 7.2+/-1.3%, P<0.05). Conversely, the mean total cell number in the media of heated arteries was higher (393+/-20 versus 328+/-17, P<0.05). Vascular preconditioning with brief WBH induces a heat shock response in the arterial wall that is associated with a significant and sustained reduction in intimal accumulation. This effect appears to be due in part to preservation of medial cell integrity and limitation of the proliferative response. These results suggest that thermal preconditioning of vascular tissue may be an effective strategy to improve long-term results after revascularization procedures.

Angioplasty, Balloon↗

PubMed1998

How body size affects middle-ear structure and function and auditory sensitivity in gekkonoid lizards.

Gekkonoid lizards increase in body size throughout life, and the present study investigates whether changes in auditory function accompany these increases. Middle-ear structures in four groups of animals, adults and juveniles of two gekkonoid species (Eublepharis macularius and Oedura marmorata), were examined. Tympanic membrane velocity and phase were also measured in all four groups. An indication of peripheral auditory function was obtained for each group by measuring compound action potentials (CAPs) from the round window membrane. The middle-ear contribution to CAP thresholds was obtained by comparing threshold levels of the CAP response with and without an intact middle-ear system. The results from these studies indicated that significant changes occurred in middle-ear structure, tympanic membrane velocity and CAP threshold between the younger and older animals. In addition, the adults of both species exhibited better auditory function when the acoustic stimulus was delivered to the tympanic membrane than when it was delivered to the columella footplate. The findings show clearly that increased body size (or age) is accompanied by functional changes in the auditory periphery.

Action Potentials↗

PubMed1998

Management of pancreaticoduodenal artery aneurysms presenting as catastrophic intraabdominal bleeding.

BACKGROUND: Pancreaticoduodenal artery aneurysms (PDAs) are rare, accounting for only 2% of all visceral artery aneurysms. The majority of reported cases of patients with PDA have presented subsequent to rupture. Presentation without rupture also has been reported and is often associated with abdominal discomfort or diagnosed incidentally on radiologic studies. PDA rupture is associated with a high mortality rate, with fatal bleeding into the retroperitoneal space, intraperitoneal cavity, or gastrointestinal tract. METHODS: This article reports two cases of ruptured PDA, both presenting as catastrophic intraabdominal bleeding and both treated successfully at celiotomy. In addition, the literature concerning PDA is reviewed. RESULTS: Only 11 cases of PDA associated with sudden, severe abdominal pain and shock have been described. The mortality rate in these 11 cases was 36%, with half the patients not reaching the operating room alive. Successful management includes rapid resuscitation and control of the bleeding site with minimal pancreatic dissection, angiography for confirmation of vascular control and anatomic localization, and further definitive treatment if obliteration is incomplete. CONCLUSIONS: The aneurysm should be obliterated whenever possible to avoid both rebleeding and local complications related to mass effect such as pancreatic duct obstruction or erosion of the mass into neighboring structures. With appropriate and expeditious treatment, these gravely ill patients can be managed effectively and good outcomes obtained.

Aged↗

PubMed1997

Antisense basic fibroblast growth factor gene transfer reduces neointimal thickening after arterial injury.

PURPOSE: To determine whether synthesis of endogenous basic fibroblast growth factor (bFGF) after arterial injury is critical to the intimal thickening response, intraluminal adenoviral gene transfer of an antisense bFGF (Ad.ASbFGF) transgene was used to inhibit the subsequent synthesis of bFGF protein after injury. METHODS: Sprague-Dawley rats underwent balloon catheter carotid artery injury and in vivo gene transfer. Isolated segments of rat common carotid artery were infected with an adenoviral vector encoding an antisense bFGF transcript at concentrations of 2 x 10(9), 1 x 10(10), or 1 x 10(11) pfu/ml. Control rats were treated with either a control adenovirus encoding the beta-galactosidase gene, (Ad.lacZ), at 1 x 10(10), or 1 x 10(11) pfu/ml, or phosphate-buffered saline solution (vehicle). Two weeks after injury the rats were killed and perfusion-fixed. Cross-sectional areas of the carotid arterial intima and media were measured by planimetry, and the intima/media ratio (I/M) was calculated for each vessel. RESULTS: The mean I/M for each Ad.ASbFGF group and controls were compared and the significance assessed by analysis of variance. At two weeks after injury, the highest dose of Ad.ASbFGF, 1 x 10(11) pfu/ml, resulted in a near total inhibition of thickening (I/M = 0.14 +/- 0.04, mean +/- SEM) when compared with phosphate-buffered saline solution alone (I/M = 0.99 +/- 0.07), or Ad.lacZ 1 x 10(10) pfu/ml (I/M = 1.01 +/- 0.10) control treatments (p < 0.01). A tenfold lower dose of Ad.ASbFGF, 1 x 10(10) pfu/ml, also caused significant reduction in intimal thickening (I/M = 0.39 +/- 0.07, p < 0.01). Treatment with 2 x 10(9) pfu/ml Ad.ASbFGF did not significantly limit intimal thickening (I/M = 0.72 +/- 0.12). CONCLUSIONS: Inhibition of bFGF synthesis in vivo using an antisense RNA strategy significantly inhibits intimal thickening after arterial balloon injury. This study suggests that continued bFGF synthesis contributes to intimal thickening after arterial injury, and that antisense bFGF may represent an effective strategy in limiting restenosis after angioplasty.

Adenoviruses, Human↗