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Biomedical subjects

J A Horton

Publications and source records attributed to J A Horton.

At least 19 recordsLinked to original sources
PubMed2006

Effects of radiation therapy on chondrocytes in vitro.

The negative irradiation complications of growth loss leading to limb length asymmetry and pathological fracture incurred following radiation therapy in pediatric patients has led to a renewed interest in understanding the specific effects of irradiation on the growth plate and the surrounding bone. In the present report, we examined the radiation therapy effects on primary rat growth cartilage chondrocytes in order to determine the chondrocyte radiosensitivity relative to other bone cell constituents and tumor cells, the postirradiation temporal progression of radiation-induced alterations in chondrocyte function, and the time course for the functional restoration of chondrocyte pathways that drive the eventual recovery in growth function. We employed an in vitro primary rat costochondral growth cartilage cell culture model system to evaluate the radiation therapy effects on proliferative chondrocytes using serial radiation doses (0-20 Gy) that are well within the clinically relevant range. Following irradiation, all of the following occurred in a dose-dependent manner: proliferation decreased, cytotoxicity increased, several markers of apoptosis increased, markers of radiation-induced cellular differentiation increased, and cell synthetic activity was disturbed. Alterations in proliferation, cell death, and induction of apoptosis are likely due to a transient radiation-induced derangement of the parathyroid hormone-related protein-Indian hedgehog proliferation-maturation pathway. Alterations in cellular differentiation and cell synthetic activity are novel observations for chondrocytes. Further, these results correspond very well to our previous work in an in vivo Sprague-Dawley rat model, making this model particularly relevant to researching the radiation therapy effects on longitudinal growth.

Alkaline Phosphatase↗
PubMed2006

Density and structural changes in the bone of growing rats after weekly alendronate administration with and without a methotrexate challenge.

Alendronate (ALN) and other bisphosphonates have been used successfully in pediatric patients with osteopenia secondary to connective tissue diseases. Loss of growth in height has not been reported, but concerns remain regarding the effect of these potent antiresorptive agents when used in children and adolescents. High-dose methotrexate (MTX) and other chemotherapy drugs have been implicated in osteoporosis and a high fracture incidence in survivors of childhood cancers and are also associated with osteopenia in adult animals. The effect of high dose MTX on bone density during rapid skeletal growth, however, has not been widely studied, nor has the potentially therapeutic effect of bisphosphonates in this setting. We examined the effects of ALN and MTX administration, alone and in combination, on bone density, morphology, mechanical strength, and longitudinal growth in normal growing rats. Sprague-Dawley rats were given ALN once weekly (0.3 mg/kg) from 5 to 11 weeks of age, with and without a course of methotrexate (MTX) given daily in weeks 1 and 3 (0.75 mg/kg/day). Twenty-four animals were randomly divided into four groups: Control (vehicle), ALN alone, ALN + MTX, and MTX alone. After 6 weeks, the femora, tibiae, and lumbar spine were studied by dual-energy X-ray absorptiometry, peripheral quantitative computed tomography, mechanical strength testing, microradiography, light microscopy, and by determination of ash weights and bone lengths. ALN treatment increased bone mineral density (BMD) by 23% to 68%. The largest increases in the femur occurred in the distal third where endochondral bone growth was greatest and included large increases in trabecular bone and total cross-sectional area. ALN + MTX produced similar effects to ALN alone. MTX only reduced BMD by 8% in the vertebrae, but not significantly at other sites. MTX also led to femoral length reductions of 2.9%. The small reductions in BMD due to MTX were overwhelmed by the increases due to ALN, whereas the length loss was unaffected. Transverse density banding corresponding to weekly ALN administrations were clearly evident radiographically throughout the growing skeleton, likely due to decreased resorption and possibly increased mineralization in the bands. ALN or ALN + MTX treatment also led to increases in mechanical strength in the femora. Although MTX administration during growth leads to some BMD reduction, ALN given with MTX eliminates this reduction and in fact bone density and strength increase above control levels.

Alendronate↗
PubMed2005

The electrochemical evaluation of a Zr-based bulk metallic glass in a phosphate-buffered saline electrolyte.

Bulk metallic glasses (BMGs) represent an emerging class of materials with an amorphous structure and a unique combination of properties. The objectives of this investigation were to define the electrochemical behavior of a specific Zr-based BMG alloy in a physiologically relevant environment and to compare these properties to standard, crystalline biomaterials as well as other Zr-based BMG compositions. Cyclic-anodic-polarization studies were conducted with a Zr52.5Cu17.9Ni14.6Al10.0Ti5.0 (at %) BMG in a phosphate-buffered saline electrolyte with a physiologically relevant oxygen content at 37 degrees C. The results were compared to three common, crystalline biomaterials: CoCrMo, 316L stainless steel, and Ti-6Al-4V. The BMG alloy was found to have a lower corrosion penetration rate (CPR), as compared to the 316L stainless steel, and an equivalent CPR, as compared to the CoCrMo and Ti-6Al-4V alloys. Furthermore, the BMG alloy demonstrated better localized corrosion resistance than the 316L stainless steel. However, the localized corrosion resistance of the BMG alloy was not as high as those of the CoCrMo and Ti-6Al-4V alloys in the tested environment. The excellent electrochemical properties demonstrated by the BMG alloy are combined with a low modulus and unparalleled strength. This unique combination of properties dramatically demonstrates the potential for amorphous alloys as a new generation of biomaterials.

Buffers↗
PubMed2004

Novel radioprotectant drugs for sparing radiation-induced damage to the physis.

PURPOSE: To determine if pentoxifylline, interleukin 1alpha, selenium and misoprostol can minimize damage to physeal longitudinal growth during single radiation dose exposure in an animal model. MATERIALS AND METHODS: Eighty-seven weanling Sprague-Dawley rats were randomized into 15 drug/dose groups. All groups received a single 17.5-Gy gamma-irradiation exposure to the right knee, the left limb serving as an internal control. Pentoxifylline was injected 30 min before exposure, sodium selenite and interleukin 1alpha 24 h before exposure and misoprostol 2 h before exposure. Positive controls received 17.5 Gy. At 6 weeks, animals were sacrificed, the hind limb lengths were measured and detailed histomorphometric analysis was performed. RESULTS: Statistically significant reductions (p < or = 0.03) in mean limb length discrepancy compared with irradiation alone were seen following administration of pentoxifylline (50 mg kg(-1)), interleukin 1alpha (15 mcg kg(-1)), selenium (5 mg kg(-1)) and misoprostol (20 mg kg(-1)). Histomorphometric endpoints and growth rate remained altered at 6 weeks despite treatment, but length discrepancy reduction was highly correlated with the appearance of regenerative clones. CONCLUSIONS: Each drug reduced the amount of anticipated growth arrest in the animal model and some compared favourably in magnitude with that previously demonstrated for the established radioprotectant drug amifostine. Restoration of growth appears related to appearance of regenerative clones.

Animals↗
PubMed1999

Prevalence of self-reported nutrition-related health problems in the Lower Mississippi Delta.

OBJECTIVES: The purpose of this study was to assess demographic and geographic differences in prevalence of self-reported nutrition-related health problems in Arkansas, Louisiana, and Mississippi. METHODS: The authors analyzed 1991 and 1993 Behavioral Risk Factor Surveillance System data for adults 18 years or older. RESULTS: Less educated African American women and women of other minority groups who were aged 35 to 64 years reported the highest prevalence of health problems. Geographic differences involved prevalence of hypertension, health status, and insurance status. CONCLUSIONS: Specific demographic subgroups and geographic areas with a high risk of health problems are in particular need of targeted interventions.

Adult↗
PubMed1998

Does refrigeration of urine alter culture results in hospitalized patients with neurogenic bladders?

A prospective, blinded study of 40 hospitalized spinal cord injured (SCI) patients was conducted to evaluate the effects of refrigeration on urinalysis and culture results. Urine samples were divided, with one aliquot examined within 4 hours and the other after 24 hours of refrigeration. Comparisons using Wilcoxon Signed Rank analysis showed no significant difference between fresh and refrigerated samples in white blood cell (WBC) count (z = -0.353, p = 0.724), number of bacteria (z = -0.772, p = 0.440), leukocytes (z = -0.277, p = 0.782), or colony counts of E. fecalis, E. coli, Citrobacter, Pseudomonas, Streptococcus, Yeast, or Acinetobacter (z = -1.00, p = 0.317; z = 0.00, p = 1.0; z = 0.00, p = 1.0; z = 0.00, p = 1.0; z = -1.00, p = 0.317; z = 0.00, p = 1.0; z = 0.00, p = 1.0, respectively). A statistically significant difference between fresh and refrigerated samples was found with "mixed" organisms (z = -2.565, p = 0.010) and a difference approaching significance was found with Staph aureus (z = -1.841, p = 0.066), both with colony counts of less than 50 k. No changes in cultures or colony counts occurred following refrigeration that would have resulted in altered treatment regimens. This study indicates that refrigeration of urine samples for up to 24 hours in the hospital setting rarely causes changes in identified organism type and causes no clinically significant changes in urinalysis or urine culture results in SCI patients.

Colony Count, Microbial↗
PubMed1997

Risk factors for human T-cell lymphotropic virus types I and II (HTLV-I and -II) in blood donors: the Retrovirus Epidemiology Donor Study. NHLBI Retrovirus Epidemiology Donor Study.

In the United States, blood donors have been routinely screened for human T-cell lymphotropic virus (HTLV) since 1988. HTLV-I and -II seropositive blood donors have been identified through confirmatory testing at five participating blood centers and frequency-matched seronegative controls provided information on potential HTLV sociodemographic, parenteral, and sexual risk factors during structured interviews. After adjustment, low educational attainment; accidental needlesticks or cuts; prior blood transfusion; > or = 7 sex partners; and a sex partner from an HTLV-I endemic area were significantly associated with both HTLV-I and -II. Gender did not modify the odds ratios (OR) in the final logistic regression models, despite apparent male-female differences in gender-specific bivariable analysis. Injection drug use (IDU) or having sex with an IDUs were significant risks for HTLV-II, but not for HTLV-I. The OR for donors who had IDU sex partners was 20.6 times higher than those who did not. For IDUs, the OR was increased 10.5 times over nonusers. Abortion was a significant HTLV-II risk factor for women. Our findings indicate that IDU and sex with IDUs are important risk factors for HTLV-II transmission, even among low-risk populations such as blood donors.

Adult↗
PubMed1996

Antepartum screening in the office-based practice: findings from the collaborative Ambulatory Research Network.

OBJECTIVE: To examine utilization patterns of four antepartum screening tests by office-based obstetricians. METHODS: The population surveyed was the Collaborative Ambulatory Research Network, a voluntary subset of 550 ACOG fellows from 130 practices participating in data collection regarding ambulatory practices. Responses from self-administered questionnaires concerning screening for hepatitis B, gestational diabetes, neural tube defects, and trisomy 21 were analyzed. RESULTS: Hepatitis screening was performed by all practices with 95% (2750 of 2886) of women tested; however, only 55% (six of 11) of at-risk newborns received treatment. For gestational diabetes screening, 94% (116 of 124) administer a 50-g glucose load to all parturients, regardless of risk factors, two-thirds initiate further testing for a 1-hour post-load glucose of 140 mg/dL or greater, and 34% do so at lower glucose levels (130-135 mg/dL). For neural tube defect screening, 92% (95 of 103) offer maternal serum alpha-fetoprotein (MSAFP) screening although when results are elevated, further recommendations are varied. For women under 35 years of age, 84% (87 of 103) offer serum screening for trisomy 21 risk, most (68%) with double or triple (MSAFP, hCG, and estriol) markers. For women over 35 years, a majority (87%) offer serum screening, although half do so only if amniocentesis is declined for age risk alone. The relatively high initial positive rate and poor specificity of serum screening were underappreciated by a large number of respondents. CONCLUSION: Increased initial and continuing education of antenatal care providers is warranted if these screening tools are to perform optimally within office practices.

Adolescent↗
PubMed1995

Temporary balloon test occlusion of the internal carotid artery: experience in 500 cases.

PURPOSE: To describe experience with 500 temporary balloon occlusions of the internal carotid artery, with particular emphasis on the techniques and complications. METHODS: Temporary occlusion of the internal carotid artery was accomplished endovascularly using various balloon-catheter combinations. These temporary balloon occlusions were combined, when possible, with cerebral blood flow analysis with stable xenon-enhanced CT. RESULTS: Complications related to this procedure occurred in 16 (3.2%) patients. Eight (1.6%) patients had asymptomatic complications. There were 8 who experienced neurologic changes. Six (1.2%) of these were transient; two (0.4%) were permanent. There were no deaths. CONCLUSIONS: Temporary balloon occlusion of the internal carotid artery, believed helpful in identifying patients at risk of stroke during abrupt carotid artery sacrifice, can be performed with an acceptably low complication rate.

Aortic Dissection↗
PubMed1995

The efficacy of particulate embolization combined with stereotactic radiosurgery for treatment of large arteriovenous malformations of the brain.

PURPOSE: To evaluate the efficacy of combined particulate embolization and single-stage stereotactic radiosurgery in the treatment of large arteriovenous malformations (AVMs) of the brain. METHODS: Twenty-four patients with large brain AVMs (diameter > 3.0 cm; volume > 14 cm3), who had previously undergone particulate embolization and stereotactic radiosurgery, were retrospectively evaluated 2 or more years after radiosurgery. RESULTS: In 12 (50%) of these patients there was complete AVM obliteration, comparing favorably with a 58% obliteration rate in a group of AVMs having a 4- to 10-cm3 volume, treated by radiosurgery alone. Recanalization of embolized, but not radiated, AVM segments was identified in 3 (12%) patients. However, long-term occlusion was demonstrated in the embolized portions of most AVMs subsequently treated by radiosurgery. Complications included 1 (4%) patient with a mild upper extremity paresis after radiosurgery and 2 (8%) patients with transient neurologic deficits after embolization. CONCLUSION: Combined embolization and stereotactic radiosurgery was more efficacious than radiosurgery alone for large brain AVMs. Recanalization after embolization did occur but was a relatively minor cause of treatment failure.

Cerebral Angiography↗
PubMed1994

Physical characteristics of balloon catheter systems used in temporary cerebral artery occlusion.

PURPOSE: To compare and contrast the physical characteristics of balloon catheter systems used for temporary cerebrovascular occlusion. METHOD: Commonly used temporary occlusion systems were evaluated to determine: (a) balloon compliance; (b) balloon diameter versus volume; (c) balloon pressure versus volume; (d) simulated vessel wall pressure versus volume; (e) balloon failure volume; and (f) balloon deflation rate. Observations were made concerning construction differences that affect the potential safety of a balloon system or the way it is used. RESULTS: The nondetachable balloon system demonstrating the best compliance characteristics and lowest radial pressure generation was the nondetachable silicone balloon (Interventional Therapeutics Corporation, San Francisco, Calif). Diameter versus volume curves for all systems reveal an initial nonlinear expansion that could contribute to vessel overexpansion during occlusion. CONCLUSION: Balloon systems vary in construction, method of introduction, and compliance. Knowledge of these characteristics, as well as of nonlinear balloon expansion, should aid balloon selection and appropriate use while helping to minimize complications.

Animals↗
PubMed1994

Transient severe brain stem depression during intraarterial papaverine infusion for cerebral vasospasm.

A 63-year-old woman had severe, symptomatic cerebral vasospasm secondary to subarachnoid hemorrhage. We initiated simultaneous infusions of papaverine into her left vertebral and left internal carotid arteries. Twenty-five minutes after the infusions had begun, the patient had a transient reaction of respiratory arrest followed by rapid, progressive loss of brain stem function.

Apnea↗
PubMed1994

[15O]H2O positron emission tomography determination of cerebral blood flow during balloon test occlusion of the internal carotid artery.

PURPOSE: To determine the utility of [15O]H2O positron emission tomography (PET) for the quantitative determination of cerebral blood flow in patients undergoing balloon test occlusion of the internal carotid artery. METHODS: Twenty-two [15O]H2O PET cerebral blood flow studies were completed on 20 patients for whom temporary or permanent occlusion of the internal carotid artery was being considered because of skull base tumor or internal carotid artery aneurysm. In each study, cerebral blood flow was determined during temporary balloon internal carotid artery occlusion, and again after deflation and removal of the balloon from the internal carotid artery. RESULTS: Patients were divided into three groups based on clinical and cerebral blood flow response to balloon test occlusion. Studies were classified as group I when associated with no clinical symptomatology and with a cerebral blood flow decrease of less than 10 mL/100 g per minute (16 of 22 patients); as group II when there was no clinical symptomatology and cerebral blood flow fell to 25 to 35 mL/100 g per minute on the occluded side (5 of 22); and as group III when the patient was clinically unable to tolerate test occlusion and had a cerebral blood flow of less than 20 mL/100 g per minute on the occluded side (1 of 22). Neurologic sequelae developed in none of the eight group I patients later undergoing permanent internal carotid artery occlusion. Cerebral infarction developed subsequently in the one group II patient who underwent internal carotid artery occlusion. CONCLUSION: During internal carotid artery balloon test occlusion, [15O] H2O PET determination of cerebral blood flow allows rapid quantitative determination of cerebral blood flow throughout the entire brain, predicting the adequacy of collateral flow after permanent occlusion. All patients were able to tolerate the [15O]H2O PET cerebral blood flow determination, and there were no complications of the procedure.

Aneurysm↗
PubMed1994

Stroke risk after abrupt internal carotid artery sacrifice: accuracy of preoperative assessment with balloon test occlusion and stable xenon-enhanced CT.

PURPOSE: To evaluate stable xenon-enhanced CT cerebral blood flow with balloon test occlusion as a predictor of stroke risk in internal carotid artery sacrifice. METHODS: Abrupt internal carotid artery occlusion was performed by surgical or endovascular means below the origin of the ophthalmic artery in 31 normotensive patients who were assessed preoperatively by a 15-minute clinical balloon test occlusion followed by an internal carotid artery-occluded xenon CT cerebral blood flow study. RESULTS: One patient, who passed the clinical test occlusion but exhibited regions of cerebral blood flow less than 30 mL/100 g per minute on the occlusion xenon CT cerebral blood flow study went on to have a fatal stroke corresponding exactly to the region of reduced blood flow. Thirty patients passed both components of the preoperative stroke-risk assessment. Neuroimaging demonstrated possible flow-related infarctions, which subsequently developed in three patients. Two patients were asymptomatic, and one patient was left with a mild residual hemiparesis. CONCLUSIONS: Our protocol provided a statistically significant reduction in subsequent infarction rate and infarction-related death rate when compared with a control group of normotensive abrupt internal carotid artery occlusion patients who did not undergo any preoperative stroke-risk assessment (reported in the literature). The estimated false-negative rate for our preoperative assessment protocol ranged from 3.3% to 10% depending on the assessment of the cause of the three potentially flow-related infarctions. Although life-threatening major vascular territory infarctions have been avoided, our protocol is less sensitive to changes predicting smaller, often minimally symptomatic, vascular border zone infarctions and does not predict postoperative thromboembolic strokes.

Adolescent↗