ABSTRACT
BACKGROUND: Hyperuricosuria is a condition that predisposes dogs to urate urolithiasis. A mutation that causes canine hyperuricosuria was previously identified in 3 unrelated dog breeds. The occurrence of the mutation in additional breeds was not determined. HYPOTHESIS/OBJECTIVES: Identify additional breeds that have the hyperuricosuria mutation and estimate the mutant allele frequency in those breeds. ANIMALS: Three thousand five hundred and thirty dogs from 127 different breeds were screened for the hyperuricosuria mutation. METHODS: DNA samples were genotyped by pyrosequencing and allele-specific polymerase chain reaction methods. RESULTS: Mutant allele frequencies that range from 0.001 to 0.15 were identified in the American Staffordshire Terrier, Australian Shepherd, German Shepherd Dog, Giant Schnauzer, Parson (Jack) Russell Terrier, Labrador Retriever, Large Munsterlander, Pomeranian, South African Boerboel, and Weimaraner breeds. CONCLUSIONS AND CLINICAL IMPORTANCE: The hyperuricosuria mutation has been identified in several unrelated dog breeds. The mutant allele frequencies vary among breeds and can be used to determine an appropriate breeding plan for each breed. A DNA test is available and may be used by breeders to decrease the mutant allele frequency in breeds that carry the mutation. In addition, veterinarians may use the test as a diagnostic tool to identify the cause of urate urolithiasis.
Subject(s)
Dog Diseases/genetics , Genetic Predisposition to Disease , Uric Acid/urine , Animals , Dog Diseases/urine , Dogs , MutationABSTRACT
BACKGROUND: Catastrophic fractures are among the most common cause of fatalities in racehorses. Several factors, including genetics, likely contribute to increased risk for fatal injuries. A variant in the procollagen-lysine, 2-oxoglutarate 5-dioxygenase1 gene (PLOD1 c.2032G>A) was shown to cause Warmblood fragile foal syndrome type 1 (WFFS), a fatal recessive defect of the connective tissue. Screening of multiple horse breeds identified the presence of the WFFS allele in the Thoroughbred. PLOD1 is involved in cross-linking of collagen fibrils and thus could potentially increase the risk of catastrophic breakdown. OBJECTIVES: Estimate the frequency of the WFFS allele (PLOD1 c.2032G>A) and determine if it is a risk factor for catastrophic breakdown in the Thoroughbred. STUDY DESIGN: Case-control genetic study. METHODS: Genomic DNA from hair and/or tissue samples was genotyped for the WFFS allele. Fisher's Exact tests were performed to compare allele and carrier frequencies between the case cohort (catastrophic breakdown, n = 22) and several cohorts with no record of injury (n = 138 raced/trained at same track and season and n = 185 older than 7 years and raced during same season), nonracers (n = 92), and a random sample without consideration for racing history (n = 279). RESULTS: The frequency of the PLOD1 c.2032G>A variant in the Thoroughbred breed is low (1.2%). Seventeen of 716 Thoroughbreds tested were carriers (2.4%) and no WFFS homozygotes were detected. Only one catastrophic breakdown case carried the WFFS allele. No statistically significant difference in allele or carrier frequency was identified between case and control cohorts (P>0.05 in all comparisons performed). MAIN LIMITATIONS: This study evaluated cases from one single track. CONCLUSIONS: This study demonstrated that the PLOD1 c.2032G>A associated with WFFS is present at very low frequency in Thoroughbreds and is not a genetic risk factor for catastrophic breakdown.
Subject(s)
Horse Diseases/genetics , Alleles , Animals , Breeding , Gene Frequency , Horses , Mutation , Procollagen-Lysine, 2-Oxoglutarate 5-DioxygenaseABSTRACT
During the BASALT research program, real (nonsimulated) geological and biological science was accomplished through a series of extravehicular activities (EVAs) under simulated Mars mission conditions. These EVAs were supported by a Mission Support Center (MSC) that included an on-site, colocated Science Support Team (SST). The SST was composed of scientists from a variety of disciplines and operations researchers who provided scientific and technical expertise to the crew while each EVA was being conducted (intra-EVA). SST management and organization developed under operational conditions that included Mars-like communication latencies, bandwidth constraints, and EVA plans that were infused with Mars analog field science objectives. This paper focuses on the SST workspace considerations such as science team roles, physical layout, communication interactions, operational techniques, and work support technology. Over the course of BASALT field deployments to Idaho and Hawai'i, the SST team made several changes of note to increase both productivity and efficiency. For example, new roles were added for more effective management of technical discussions, and the layout of the SST workspace evolved multiple times during the deployments. SST members' reflexive adjustments resulted in a layout that prioritized face-to-face discussions over face-to-data displays, highlighting the importance of interpersonal communication during SST decision-making. In tandem with these workspace adjustments, a range of operational techniques were developed to help the SST manage discussions and information flow under time pressure.
Subject(s)
Astronauts/psychology , Extravehicular Activity , Mars , Space Simulation/methods , Communication , Decision Making , Decision Support Techniques , Efficiency , Hawaii , Humans , Idaho , Interpersonal Relations , Satellite Communications , Space Simulation/psychologyABSTRACT
The Biologic Analog Science Associated with Lava Terrains (BASALT) research project is investigating tools, techniques, and strategies for conducting Mars scientific exploration extravehicular activity (EVA). This has been accomplished through three science-driven terrestrial field tests (BASALT-1, BASALT-2, and BASALT-3) during which the iterative development, testing, assessment, and refinement of concepts of operations (ConOps) and capabilities were conducted. ConOps are the instantiation of operational design elements that guide the organization and flow of personnel, communication, hardware, software, and data products to enable a mission concept. Capabilities include the hardware, software, data products, and protocols that comprise and enable the ConOps. This paper describes the simulation quality and acceptability of the Mars-forward ConOps evaluated during BASALT-2. It also presents the level of mission enhancement and acceptability of the associated Mars-forward capabilities. Together, these results inform science operations for human planetary exploration.
Subject(s)
Exobiology/methods , Extravehicular Activity , Mars , Operations Research , Space Simulation/methods , Exobiology/instrumentation , Humans , Space Simulation/instrumentationABSTRACT
Endochondral ossification in fracture healing of rats at 4, 8, 11, 14, and 21 days was analyzed using immunological and molecular probes for markers of the chondrocyte and osteoblast phenotype. These markers were osteocalcin, type I and type II collagen, including the probes homologous to the alternatively spliced forms of alpha 1 type II collagen, type IIA and type IIB. Histologic examination was performed on serial sections of the same tissue blocks to correlate cellular morphology with the immunohistochemical and in situ hybridization findings. At the junction of the cartilaginous and osseous tissue, an overlap of phenotype and morphology was noted. At the 8-day time point, the cells with chondrocyte morphology expressed intracellular message for osteocalcin and type I collagen. Immunohistochemical analysis of these cells also demonstrated intracellular osteocalcin. However, high levels of the type IIA collagen mRNA, which has previously been associated with less differentiated mesenchymal precursor cells, were expressed in both chondrocytes and osteoblasts. At the later time point (21 days) there was a substantial decrease in the number of cells displaying shared phenotypic characteristics. In situ hybridization and immunohistochemistry have permitted identification of an overlapping or shared phenotype in osteoblasts and chondroblasts in fracture callus. The findings raise important questions regarding the possible plasticity of mesenchymal cell phenotypes within the dynamic environment of fracture healing. Additional examination of these issues will further define factors involved in origin, differentiation, and maturation of bone and cartilage cells.
Subject(s)
Bony Callus/cytology , Cartilage/metabolism , Fracture Healing/physiology , Osteoblasts/metabolism , Animals , Calcification, Physiologic/genetics , Calcification, Physiologic/physiology , Cartilage/cytology , Cell Differentiation/genetics , Collagen/genetics , Collagen/metabolism , DNA, Complementary/metabolism , Disease Models, Animal , Female , Fracture Healing/genetics , Fractures, Bone/metabolism , Immunohistochemistry , In Situ Hybridization , Oligonucleotide Probes , Osteoblasts/cytology , Osteocalcin/genetics , Osteocalcin/metabolism , Phenotype , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Tibia/injuriesABSTRACT
The purpose of this study was to compare the density of periprosthetic bone about titanium and cobalt-chromium stems that had been inserted without cement. The analysis was done, three to four years after a total hip arthroplasty, in a retrospectively matched cohort of thirty patients. Fifteen patients had a stem that was collarless, proximally coated, and made of titanium; the other fifteen had a stem of similar design that was made of cobalt-chromium. The criteria for selection in the study included an excellent clinical and radiographic result and separately calculated modified Harris and Mayo hip scores of more than 94 points. All stems had radiographic evidence of osseous ingrowth. A comparison of the bone-mineral density about the two different types of stem with dual-energy x-ray absorptiometry revealed a significant difference only along the calcar of the femur. There was no significant difference about the remaining, preponderant portion of the proximal part of the femur. Our data suggest that the difference in the modulus of elasticity between the two types of stem had little effect on the loss of bone-mineral density in most of the proximal part of the femur after arthroplasty without cement.
Subject(s)
Bone Resorption/etiology , Femur/physiopathology , Hip Prosthesis/adverse effects , Absorptiometry, Photon , Adult , Aged , Analysis of Variance , Bone Density , Chromium Alloys/chemistry , Cohort Studies , Elasticity , Female , Femur/diagnostic imaging , Hip Prosthesis/methods , Humans , Male , Middle Aged , Prosthesis Design , Retrospective Studies , Statistics, Nonparametric , Stress, Mechanical , Titanium/chemistry , Weight-BearingABSTRACT
Thirty-five patients were managed operatively after failure of an anterior cervical discectomy and arthrodesis. Failure was classified as the absence of fusion without deformity but with neck pain or radiculopathy, or both; the absence of fusion after anterior or posterior dislodgment of the graft; or kyphosis due to collapse of the graft or to an unrecognized posterior soft-tissue injury. Twenty-three patients had failure of the arthrodesis without deformity (with neck pain only, neck and arm pain, radiculopathy, or myelopathy). Four patients had dislodgment of the graft; in two of them the graft migrated anteriorly after a multilevel Robinson arthrodesis, and in two it migrated posteriorly after a Cloward arthrodesis. Eight patients had a failure because of a kyphotic deformity. Five of them had had a Cloward arthrodesis; one, a discectomy; and two, a Robinson arthrodesis. Six had received allograft bone. Operative treatment of the pseudarthrosis consisted of repeat resection of the disc space in the area of the failed arthrodesis followed by repeat anterior Robinson arthrodesis with decompression of the nerve root if the patient had radiculopathy. It consisted of anterior corpectomy or vertebral-body resection and strut-grafting with reduction of the deformity if the patient had migration of the graft and kyphosis. The reoperations were performed four months to fourteen years (average, thirty-two months) after the initial operation. The duration of follow-up after the second operation averaged forty-four months (range, twenty-four to 216 months). The result was excellent for twenty-nine patients, good for one, fair for four, and poor for one. We concluded that, in patients who have persistent symptoms after an anterior cervical arthrodesis, an excellent result can be achieved with repeat anterior decompression and autogenous bone-grafting.
Subject(s)
Arthrodesis , Cervical Vertebrae/surgery , Diskectomy , Spinal Diseases/surgery , Adult , Aged , Cervical Vertebrae/diagnostic imaging , Female , Humans , Intervertebral Disc Displacement/surgery , Kyphosis/surgery , Male , Middle Aged , Radiography , Spinal Diseases/diagnostic imaging , Treatment FailureABSTRACT
An animal model was used to examine the effect of maternal alcohol administration on behaviors in the offspring which might predispose to alcoholism. Pregnant C3H mice were administered a liquid diet containing 28% ethanol-derived calories (EDC) from Gestation-Day 8 until parturition. Control animals were either pair-fed an isocaloric 0% EDC diet or received standard lab chow and water throughout pregnancy. Offspring were tested for sleep time following a challenge dose of 3.5 or 4.5 g/kg ethanol at 25 or 110 days of age or for consumption of 10% w/v ethanol in a two-bottle choice situation. The results demonstrated that prenatal exposure to alcohol did not affect alcohol-induced sleep time at either testing age or dose and that waking blood alcohol levels were similar across groups. Voluntary alcohol consumption, however, was higher in mice exposed to alcohol in utero during the initial week of testing but intake decreased to near control levels by the third week. Whether other alcohol-related behaviors are altered by prenatal alcohol exposure remains to be examined.
Subject(s)
Alcohol Drinking , Alcoholism/genetics , Prenatal Exposure Delayed Effects , Sleep Stages/drug effects , Animals , Dose-Response Relationship, Drug , Female , Humans , Male , Mice , Mice, Inbred C3H , PregnancyABSTRACT
The effects of pregnancy and lactation on alcohol consumption were examined in the C57BL mouse. Pregnant mice were given a two-bottle choice between water and 10% w/v alcohol solution from Day 5 of pregnancy, through two weeks of lactation, and an additional four weeks following the removal of nursing pups. Alcohol consumption was expressed in terms of g absolute ethanol per kg body weight and as an alcohol preference ratio (ml alcohol/ml total fluid). Alcohol consumption (g ethanol per kg body weight) fell below control values during pregnancy and lactation but increased to control levels during postlactation. Similarly, alcohol preference ratio was found to decline during pregnancy, and to further decrease during lactation, a trend that was reversed during postlactation. The results support the findings of decreased alcohol consumption during pregnancy in alcoholic as well as nonalcoholic women.
Subject(s)
Alcohol Drinking , Lactation , Pregnancy, Animal , Animals , Female , Mice , Mice, Inbred C57BL , Pregnancy , Time FactorsABSTRACT
We implanted 57 uncemented cobalt-chrome porous-coated collarless femoral components into 51 patients (mean age 49 years). At review, five to eight years postoperatively, good or excellent results were recorded in 70% by the Mayo Clinic hip evaluation and in 84% by the Harris hip score. Revision for aseptic loosening of the femoral stem was necessary in only one hip. Thigh pain diminished with time and was present in only two hips at the time of review. Endosteal bone formation was seen at the junction of the smooth and the porous segments of the stem in 94% of hips and in 60% it continued after three years. In 90% of hips, proximal femoral atrophy did not progress after three years. Discontinuous radiolucent lines were seen around 30% of stems, most commonly in zones I, IV and VII. They were not progressive in 94% and their presence did not correlate with the clinical outcome.
Subject(s)
Hip Prosthesis , Activities of Daily Living , Adult , Aged , Chromium Alloys , Female , Femur/diagnostic imaging , Femur/surgery , Follow-Up Studies , Humans , Male , Middle Aged , Prosthesis Design , Radiography , Reoperation , Surveys and QuestionnairesABSTRACT
Successful approaches to race determination of unidentified human remains have been developed by anatomists and physical anthropologists, but few quantitative methods are available for distinguishing American Indian crania from those of whites. The leading method in use today is particularly ineffective in its placement of American Indian skulls from the western regions of the United States. Recent development and testing of a new metric method suggests a much more effective technique. The method involves six breadth and projection measurements of the midfacial skeleton, the calculation of three indices, and a simple direct reading of results. The method has the additional advantage of use in the autopsy room with minimal dissection of soft tissue required. Based upon a less extensive test of East Asian and Arctic Mongoloid crania, the method appears to be even more effective in separating them from the sharp featured whites. Larger samples of American blacks and Polynesians are presently under study and these also appear to separate quite readily from whites using the same or similar sectioning values.
Subject(s)
Cephalometry , Indians, North American , White People , Face/anatomy & histology , Female , Humans , Male , United StatesABSTRACT
In 1973-1974 Stanley N. Cohen of Stanford and Herbert W. Boyer of the University of California, San Francisco, developed a laboratory process for joining and replicating DNA from different species. In 1974 Stanford and UC applied for a patent on the recombinant DNA process; the U.S. Patent Office granted it in 1980. This essay describes how the patenting procedure was shaped by the concurrent recombinant DNA controversy, tension over the commercialization of academic biology, governmental deliberations over the regulation of genetic engineering research, and national expectations for high technology as a boost to the American economy. The essay concludes with a discussion of the patent as a turning point in the commercialization of molecular biology and a harbinger of the social and ethical issues associated with biotechnology today.
Subject(s)
DNA, Recombinant/history , Molecular Biology/history , Patents as Topic/history , Biotechnology/economics , Biotechnology/history , Biotechnology/legislation & jurisprudence , Commerce/history , DNA, Recombinant/economics , History, 20th Century , Molecular Biology/economics , Molecular Biology/legislation & jurisprudence , United StatesABSTRACT
Oliguria is common in critically ill patients and may result from prerenal, renal, and postrenal causes. Oliguria also frequently develops in patients with normal concentrations of blood urea nitrogen and creatinine. Most of these patients do not develop renal failure. The authors prospectively studied 100 patients admitted to the ICU to determine the etiology of oliguria in these patients. Eighteen patients (18%) developed oliguria (less than 0.33 ml.kg-1.h-1 X 2 h). Seven and eleven patients were felt on clinical assessment to be hypovolemic or normovolemic, respectively. Compared with the hypovolemic patients, the normovolemic oliguric patients had significantly lower serum osmolalities (278 +/- 3 vs. 290 +/- 5 mOsm/kg H2O) and serum sodium concentrations (138 +/- 3 vs. 132 +/- 1 mEq/l). In addition, normovolemic patients had significantly higher urine sodium concentrations (83 +/- 12 vs. 13 +/- 2 mEq/l), fractional excretion of sodium (1.14 +/- 0.2 vs. 0.15 +/- 0.03), and renal failure indices (1.5 +/- 0.3 vs. 0.21 +/- 0.04). ADH concentrations in six hypovolemic and six normovolemic patients were increased in both groups but not significantly different. The hypovolemic patients increased their urine output from 17 +/- 2 ml/h to greater than 0.5 ml.kg-1.h-1 following a 500-ml bolus of normal saline. The normovolemic oliguric patients remained oliguric following the saline bolus (13 +/- 2 to 19 +/- 3 ml/h). The authors conclude that oliguria is common in critically ill patients and results from renal hypoperfusion and ADH excess.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Anuria/physiopathology , Kidney/physiopathology , Oliguria/physiopathology , Blood Volume , Diuresis/drug effects , Furosemide/therapeutic use , Humans , Inappropriate ADH Syndrome/complications , Inappropriate ADH Syndrome/drug therapy , Oliguria/etiology , Osmolar Concentration , Reference Values , Sodium Chloride/pharmacology , Vasopressins/bloodABSTRACT
We report a nondisplaced femoral neck and head fracture diagnosed acutely by CT scanning. This case illustrates the potential benefits of an acute femoral neck/head CT scan in obtunded polytrauma patients with high-energy femoral shaft fractures.
Subject(s)
Femoral Fractures/diagnostic imaging , Tomography, X-Ray Computed , Accidents, Traffic , Adult , Female , Femoral Fractures/pathology , Femoral Neck Fractures/diagnostic imaging , Femur Head/injuries , Hip Fractures/diagnostic imaging , Hip Fractures/pathology , HumansABSTRACT
To provide baseline outcome data for a new lumbar microinvasive diskectomy done with standard arthroscopic instrumentation, we retrospectively reviewed the cases of 190 patients. All patients were assessed by a modified MacNab outcome classification with a minimum of a 2-year follow-up. All complications of this procedure were reported as well. No previous outcome data are available for this procedure, since it has been done primarily at one center, by the same surgeon, using his previously reported techniques. Results were good or excellent in 175 patients and fair or poor in 15. Complications were not severe and were easily remedied. This success rate is comparable to rates reported for other minimally invasive operations on the lumbar spine. This new technique of minimally invasive lumbar spine surgery provides minimal morbidity and a long-term outcome comparable to that of other standard procedures. The added benefits of using standard arthroscopic instrumentation are discussed.
Subject(s)
Endoscopy/methods , Intervertebral Disc Displacement , Lumbar Vertebrae , Adult , Epidural Space , Female , Humans , Male , Treatment OutcomeABSTRACT
The literature provides little data to guide surgical management of spinal stenosis adjacent to previous lumbar fusion. Thirty-three consecutive patients who had surgical decompression for spinal stenosis at the lumbar segments adjacent to a previous lumbar fusion were studied. The mean interval between fusion and the adjacent segment surgery was 94 months. Of the 33 patients, 26 were followed for 3-14 years (mean: 5 years) after adjacent segment surgery and were clinically evaluated and independently completed an outcome questionnaire. Of the 26 patients, 15 rated their outcome as completely satisfactory, 6 were neutral toward the surgery, and 5 considered their surgery a failure. The surgery was generally effective at improving or relieving lower extremity neurogenic claudication. The strongest independent predictive factor of patient dissatisfaction was ongoing postoperative low back pain (r = 0.7, p = 0.001). A higher back pain score at follow-up was associated with continued narcotic use (p = 0.001) and decreased ability to perform activities of daily living (p = 0.05). Six patients required further lumbar surgery during the follow-up period. This study provides the longest published follow-up data of surgical results for symptomatic spinal stenosis adjacent to a previously asymptomatic lumbar fusion.
Subject(s)
Lumbar Vertebrae/surgery , Postoperative Complications/surgery , Spinal Canal/surgery , Spinal Fusion/adverse effects , Spinal Stenosis/etiology , Spinal Stenosis/surgery , Adult , Aged , Female , Follow-Up Studies , Humans , Low Back Pain/etiology , Low Back Pain/pathology , Low Back Pain/surgery , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/pathology , Male , Middle Aged , Paresis/etiology , Paresis/pathology , Paresis/surgery , Postoperative Complications/etiology , Postoperative Complications/pathology , Radiography , Risk Factors , Spinal Canal/diagnostic imaging , Spinal Canal/pathology , Spinal Stenosis/pathology , Surveys and Questionnaires , Treatment OutcomeABSTRACT
We examined the in vivo alterations of human patellar bone blood flow that occur with surgical dissection of the extensor mechanism during total knee arthroplasty. A laser doppler probe was used to measure central patellar blood flow at baseline after quadriceps tenotomy, after partial fat pad excision, after lateral release, and after completion of the lateral release with superolateral geniculate sacrifice. The initial quadriceps tenotomy and medial arthrotomy decreased patellar vascularity to 60.4% of baseline. Fat pad resection initiated another 10.4% decline. The lateral release resulted in a patellar vascularity that was 43.6% of baseline. Finally, the loss of superolateral geniculate inflow reduced the patellar flow to 30.61% of baseline.
Subject(s)
Arthroplasty, Replacement, Knee , Dissection , Laser-Doppler Flowmetry , Patella/blood supply , Adipose Tissue/surgery , Aged , Analysis of Variance , Arteries/surgery , Female , Humans , Knee Joint/surgery , Male , Microcirculation/physiology , Middle Aged , Muscle, Skeletal/surgery , Osteoarthritis, Knee/surgery , Pilot Projects , Regional Blood Flow/physiology , Tendons/surgery , TourniquetsABSTRACT
This article describes a new technique to achieve access to the epidural space via a direct posterior portal. This minimally invasive technique allows treatment of disc protrusions and extrusions with full visualization and minimal dissection of the paraspinal musculature. Hemostasis, visualization, and triangulation is performed with standard arthroscopic instrumentation. The anatomy of, indications for, and advantages of this techniques are described.