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Biomedical subjects

P A Anderson

Publications and source records attributed to P A Anderson.

At least 19 recordsLinked to original sources

Guideline-based consultation to prevent anticoagulant-related bleeding. A randomized, controlled trial in a teaching hospital.

OBJECTIVE: To test the efficacy of consultation designed to prevent anticoagulant-related bleeding. DESIGN: Randomized, controlled trial. SETTING: A large teaching hospital. PATIENTS: A total of 101 patients at increased (greater than 15%) risk for major, in-hospital bleeding while starting long-term anticoagulant therapy who were identified using a validated prediction rule. INTERVENTIONS: Fifty-five patients received usual care under the direction of the attending physician who had initiated anticoagulant therapy. Forty-six patients received guideline-based consultation in addition to usual care. Guideline-based consultation included individualized review of the risks and benefits of anticoagulant therapy and, on the basis of current practice guidelines, recommendations for daily management. MEASUREMENTS: The main outcome was in-hospital bleeding, which was classified using a reliable, explicit index. RESULTS: Major or minor bleeding occurred in 17 of 55 patients (31%) receiving usual care alone, compared with 6 of 46 patients (13%) receiving consultation in addition to usual care (P = 0.03). The protective efficacy of consultation was 58% (95% CI, 3% to 82%). Consultation was associated with similar reductions in the frequencies of major bleeding (from 13% to 4%) and minor bleeding (from 18% to 9%). Consultative recommendations had an 84% compliance rate and directly affected anticoagulant management: In the consult group, nonsteroidal anti-inflammatory agents were stopped in six patients (13%), and therapeutic ranges were achieved more often for activated partial thromboplastin times (52% compared with 45% in the usual care group, P = 0.08) and for prothrombin times (47% compared with 27% in the usual care group, P less than 0.001). Nearly all housestaff and attending physicians (91%) for patients receiving consultation also reported that consultation improved housestaff learning. The consult group had a somewhat lower rate of thromboembolism in the 90 days after discharge (5% compared with 17%, P = 0.06). Death rates and mean lengths of stay were similar in the two groups. CONCLUSION: Guideline-based consultation was associated with reduction in the frequency of anticoagulant-related bleeding in patients at increased risk for major in-hospital bleeding.

Aged

A cardiac troponin T epitope conserved across phyla.

Troponin T is a thin filament protein that is important in regulating striated muscle contraction. We have raised a monoclonal antibody against rabbit cardiac troponin T, monoclonal (mAb) 13-11, that recognizes its epitope in cardiac troponin T isoforms from fish, bird, and mammal but not from frog. The number of these isoforms expressed in cardiac muscle varies among species and during development. Cardiac troponin T isoforms were not found in adult skeletal muscle, while they were expressed transiently in immature skeletal muscle. We have mapped the epitope recognized by mAb 13-11 using rabbit cardiac troponin T isoforms. Analysis of stepwise cyanogen bromide digestion, which allowed association of the epitope to regions spanning methionine residues, coupled with immunoactivity of synthetic peptides, corresponding to sequences containing methionine residues, indicated that mAb 13-11 recognized its epitope in a 17-residue sequence containing the methionine at position 68, SKPKPRPFMPNLVPPKI. Comparison of skeletal and cardiac troponin T sequences suggested that the epitope was contained within the sequence FMPNLVPPKI. Synthetic peptides PFMPNLVPPKI and FMPNLVPPKI were recognized by mAb 13-11 on slot-blots. Enzyme-linked immunosorbent assay demonstrated mAb 13-11 recognized, in order of descending affinity, the 17-, 11-, and 10-residue sequence. Preabsorption of mAb 13-11 with each of these sequences blocked the recognition of the 17-residue peptide by mAb 13-11. The domain, PFMPNLVPPKI is encoded by the 5' region of the cardiac gene exon 10 and is present in hearts across a broad range of phyla. These findings suggest that this cardiac troponin T-specific sequence confers onto myofilaments structural and functional properties unique to the heart.

Amino Acid Sequence

Effect of controlled local release of sodium fluoride on trabecular bone.

Systemic sodium fluoride has been used in the treatment of osteoporosis. Recent studies have shown that it has a positive risk/benefit ratio for use in increasing spinal trabecular bone density. However, thinning of the cortices of the long bones with a resulting increase in fracture incidence has been observed. This study was designed to determine the response of bone to sodium fluoride released from a biodegradable polymer matrix, a technique which could potentially deliver it locally to a site of need in the skeleton which has a positive response to fluoride. In one group of mature New Zealand white rabbits, cylindrical poly(D,L-lactic acid) (PLA) implants, with or without impregnated sodium fluoride, were implanted into the contralateral femoral trochanters and tibial metaphyses. In a second group, similar implants were placed in adjacent vertebrae. Four weeks postimplantation, the femora, tibiae, and vertebrae were removed, sectioned, cleaned of all but mineralized tissue, and the surfaces of the sections stained. The stained surfaces were imaged and analyzed for morphometric properties of the trabeculae. Comparing contralateral vertebrae, those exposed to sodium fluoride had significantly thickened trabeculae, with decreased spacing between them and a greater bone fraction. A similar increase in trabecular width was found in the subchondral bone of the proximal tibiae exposed to local release fluoride. Femoral sections showed no difference, possibly due to the lack of extensive trabecular bone in the region chosen for study.

Animals

Troponin T isoform expression in the normal and failing human left ventricle: a correlation with myofibrillar ATPase activity.

The expression of troponin T, a thin filament regulatory protein, was examined in normal and failing left ventricles. The samples were obtained from the hearts of patients with severe heart failure who were undergoing cardiac transplantation, and from normal adult hearts that could not be used for transplantation. Western blots of the myofibrillar proteins demonstrated two isoforms, troponin T 1 (TnT1) and troponin T 2 (TnT2). TnT2 is expressed at significantly higher levels in failing hearts (p less than 0.004). Western blots of two-dimension SDS-PAGE gels resolved two dominant spots of TnT1 and of TnT2 and several minor troponin T species. Alkaline phosphatase treatment markedly decreased the sizes of the two acidic spots while increasing the two more basic spots by a comparable amount. Myofibrillar ATPase activity had an inverse and negative linear relationship (r = 0.7, p less than 0.02) with the myofibrillar percentage of total troponin T comprised of TnT2. In that heart failure in these transplant patients had multiple bases, we propose that rather than a cause of heart failure, the disease-associated changes in troponin T isoform expression are an adaptation to abnormal myocardial function.

Adolescent

The presence and distribution of Antho-RFamide-like material in scyphomedusae.

The nervous systems of the scyphomedusae Chrysaora hysoscella, Cyanea capillata and Cyanea lamarckii (Phylum Cnidaria) were stained using an anti-serum against the anthozoan neuropeptide Antho-RFamide. Staining was widespread in all three species. In Chrysaora, the antiserum revealed nerve nets in the subumbrella and exumbrella ectoderm, in both faces of the oral lobes, and in the endoderm lining the subumbrella and exumbrella surfaces of the gastric cavity. The most prominent staining occurred in a dense plexus of neurons in the ectoderm at the base of the tentacles. This nerve net sent projections into the subumbrella ectoderm. For the most part, staining in the two species of Cyanea was similar to that in Chrysaora, with a few exceptions. These include the presence, in Cyanea, of an obvious tentacular nerve tract and nerve nets associated with clusters of cnidocytes in the tentacles. Radioimmunoassays of extracts from Chrysaora and Cyanea lamarkii revealed that both species contain large amounts of Antho-RFamide-like material (up to 55 nmol/animal). The results indicate that Antho-RFamide-like neuropeptides are widespread in scyphomedusae.

Animals

Multicystic renal dysplasia detected by prenatal ultrasonography. Natural history and results of conservative management.

In a review of 44 infants with multicystic renal dysplasia diagnosed prenatally by ultrasonography, contralateral anomalies, bilateral disease and other non-urinary congenital anomalies were rare. In approximately two-thirds of infants the lesion was impalpable and in 2 cases involution had occurred prenatally. All but 5 were managed conservatively and without complications, and partial or complete involution of the lesion occurred in more than 50% during follow-up. It was concluded that the natural history of this anomaly is usually benign and that conservative management is advisable.

Female

Natural history of obstructed and pseudo-obstructed megaureters detected by prenatal ultrasonography.

In a series of 38 patients with non-refluxing megaureters detected by prenatal ultrasonography, 89% were males and 16% had associated ipsilateral or contralateral urinary anomalies. By renographic criteria, 36% of ureters were not obstructed; renal function was never impaired initially and, on follow-up, spontaneous resolution of dilatation was common. Infective urinary calculi developed in 3 of the boys. In ureters obstructed by renographic or pressure-perfusion criteria, 79% exhibited normal renal function initially. Most such patients were managed expectantly; on follow-up, functional deterioration occurred in 2 patients, while in the remainder dilatation usually persists but without change in function.

Child, Preschool

Anterior decompression and arthrodesis of the cervical spine: long-term motor improvement. Part I--Improvement in incomplete traumatic quadriparesis.

Between 1973 and 1983, fifty-eight patients who had an incomplete spinal-cord injury secondary to a fracture or dislocation of the cervical spine were managed by anterior cervical decompression and arthrodesis with iliac bone grafts. In all patients, myelography showed that displaced fragments of bone or disc were compressing the anterior aspect of the spinal cord. Anterior decompression was performed in an attempt to improve function in the upper and lower extremities. The average interval from the injury to the decompression was thirteen months (range, one month to nine years). Two patients died of cardiopulmonary disease within two months after the operation, and one patient died eighteen months after the operation. The remaining fifty-five patients were followed for an average of six years (range, two to seventeen years). Twenty-nine patients became functional ambulators after the operation. An additional six patients who could walk before the operation had improvement in the ability to walk. Noteworthy improvement in motor-root function in the upper extremities was seen in thirty-nine patients. Only nine patients had no signs of improvement of motor function. Improvement was less in the patients in whom operative decompression had been done more than twelve months after the injury. The patients who had an extension injury to a spondylotic spine were older, and fewer of them had improvement. No patient lost neurological function as a result of the operation. Anterior decompression and arthrodesis, even when performed late after the injury, can improve neurological function in both the upper and lower extremities in many patients who have incomplete quadriplegia due to a fracture or dislocation of the cervical spine.

Adolescent

Anterior decompression and arthrodesis of the cervical spine: long-term motor improvement. Part II--Improvement in complete traumatic quadriplegia.

Fifty-one patients who had complete motor quadriplegia secondary to a fracture or dislocation of the cervical spine were managed by anterior cervical decompression and arthrodesis with iliac bone grafts between 1973 and 1983. In all patients, myelography demonstrated that displaced fragments of bone and disc were compressing the anterior aspect of the spinal cord. Decompression was performed in an attempt to gain further improvement of the motor-roots in the upper extremities and thereby to improve the ability of the patients to care for themselves. The average interval from the injury to the decompression was fifteen months (range, one month to eight years). Two patients died within two months after the operation, one had a respiratory arrest that resulted in brain damage one day after the operation, and two died from cardiovascular disease more than one year after the operation. The remaining forty-six patients were followed for an average of five years (range, two to thirteen years). Neurological improvement of at least two new functional motor-root levels was documented in seven patients and of one level, in eighteen. Increased motor strength by two or three grades was seen in six patients. Noteworthy motor improvement did not occur in the remaining twenty patients. The mean modified Barthel index (used to measure improvement in the ability to perform activities of daily living) increased from 17 to 33 (of a possible 100) points. Functionally important improvement of the caudad part of the cord occurred in only one patient. In one patient, neural injury, with loss of one motor-root level, occurred, with only partial improvement. At the latest follow-up examination, the result was poor in nine of eleven patients who had decompression eighteen months or more after the injury. Only two of these patients had any improvement in the Barthel index, and then of only 5 points each. The result also was poor in the five patients who were more than fifty-three years old; two had no improvement in the Barthel index, one improved by 5 points, and two died.

Adolescent

Response of cortical bone to local controlled release of sodium fluoride: the effect of implant insertion site.

In a previous experiment, sodium fluoride in a biodegradable polymer matrix was introduced into the femoral canal of the rabbit and bone formation was compared with contralateral controls. We noted significant bone formation, but only in the distal third of the periosteal surface of the femur. This experiment was performed to distinguish fluoride-induced periosteal bone formation from that due to the reactive osteogenic changes associated with local injury caused by the process of implantation. A proximal approach on the right leg and a distal approach on the left were used for the insertion of the implants in rabbits. Femurs were removed after 30 days and tested for stiffness and load to failure. The cross-sectional area of mineralized bone was determined at proximal, midshaft, and distal locations. Fluorescent bone tissue growth labels were injected at weekly intervals to measure the rate of new periosteal bone formation. The results were compared with a control group that received sham implants. Results showed no difference between measured properties in right and left femurs in the control group or in those exposed to fluoride. A significant increase was found in the fluoride group in load to failure, along with cross-sectional area of mineralized bone, and periosteal growth rates compared with the control group, but no difference was seen in stiffness. No difference was detected between the response proximally and distally in the fluoride group regardless of the location of insertion. There were no detectable changes in serum fluoride level after implantation of the poly L-lactic acid/sodium fluoride matrix. These results show that fluoride exerts its osteogenic effects equally at proximal, midshaft, and distal regions of diaphyseal bone and is uninfluenced by the site of local injury due to insertion of the implant.

Animals

Two cases of fatal atlantoaxial distraction injury without fracture or rotation.

Atlantoaxial injuries, regardless of mechanism, typically result in bony injury. We present two unusual cases of fatal traumatic C-1-C-2 distraction without associated fracture or rotation. The ligamentous anatomy, common underlying structural/medical predispositions, and the possible mechanism of injury are discussed.

Adult

Dietary protein and chronic toxicity of 1,2-dimethylhydrazine fed to mice.

1,2-Dimethylhydrazine-HCl (DMH-2HCl) is derived from the natural toxin cycasin, and is extensively used to induce cancers in experiments with rodents. We examined the toxicity of DMH-2HCl, incorporated into purified diets varying in protein, to determine concentrations compatible with long-term survival in B6C3H1 mice. Initial studies showed single-dose oral LD50 values (95% confidence intervals) of 26 (18-32) mg DMH-2HCl/kg body weight for males, and 60 (53-65) for females. A 6-wk study was performed with diets containing 10 or 40% soybean protein with doses of 0, 11.25, 22.5, 45, 90, and 180 mg DMH-2HCl/kg diet. All mice fed the highest dose were removed from the study due to severe toxicity. Declines in food consumption and body weight occurred in both sexes, accelerated with increasing log(DMH) dose, and were substantially more severe in groups fed 10% protein. A 5-mo study was subsequently performed with male mice fed 10 or 40% protein diets containing doses of 0, 15, 30, or 45 mg DMH-2HCl/kg diet. In this longer study, dose-related declines of food intake and body weight were also more pronounced with 10% protein. Histopathologic examination of samples from 29 organs/tissues revealed hepatic changes most commonly, and these were more severe at higher DMH levels. Lesions ranged from focal centrilobular hepatocellular necrosis to severe toxic hepatitis, associated with lobular disorganization and hepatocellular hypertrophy. Frequent dose-dependent lesions were also found in kidneys, adrenals, and heart. Renal changes included focal subcapsular fibrosis with atrophy, and hyperplasia of the tubular epithelium. Adrenal cortical hypertrophy was noted at the two highest DMH doses. Focal cardiac myocytolysis was also noted at high DMH doses. Renal damage occurred only rarely in the absence of liver pathology, and adrenal hypertrophy only rarely without renal damage. Cardiac myocytolysis was found in 14% of mice without hepatic, renal, or adrenal damage, but in 62% of those with lesions in each of those organs. No evidence of gastrointestinal toxicity was observed. Hepatic, renal, and adrenal lesions were more frequent and severe in mice fed the low-protein diet. The protective effect of high protein was DMH-dose dependent. The lower doses in these studies could be used to investigate effects of diet, cocarcinogens, or chemopreventative agents on carcinogenesis resulting from chronic, low-level dietary exposure to DMH.

1,2-Dimethylhydrazine

Flexion distraction and chance injuries to the thoracolumbar spine.

Seat belt legislation has resulted in increased restraint use by passengers in automobiles in Washington State. At Harborview Medical Center in Seattle, we have observed an increased incidence of seat belt-related injuries. Twenty cases of Chance-type thoracolumbar flexion-distraction fractures were reviewed retrospectively. Thirteen patients (65%) had associated life-threatening intra-abdominal trauma. Twelve of these patients had bowel wall injury. Ninety percent of the children had combined abdominal and spinal injury. Operative treatment of the spinal injury resulted in correction of lumbar kyphosis and lower incidence of back pain than nonoperatively managed cases. We recommend careful physical and radiographic examination of all patients with significant abrasion or bruising about the pelvis or abdomen related to seat belts. Victims of automobile crashes who are treated for bowel injury require thoracolumbar radiographs. Similarly, patients with Chance-type fractures should undergo diagnostic peritoneal lavage or computerized abdominal tomography.

Abdominal Injuries

The epidemiology of seatbelt-associated injuries.

This study examined the frequency of spine and abdominal injuries to motor vehicle occupant crash victims, the relationship between the two types of injuries, and the association with restraint use. There were 303 motor vehicle occupants treated at a regional trauma center for spine and/or abdominal injuries over a 5-year period. Patients with Chance-type fractures of the lumbar spine were much more likely to be rear seat passengers and to be using a lap belt than were patients with other types of spinal injuries. Similarly, patients with hollow viscus injuries were more likely to be rear seat passengers and to be lap belted than were patients with injuries to the spleen, liver, pancreas, or kidneys. Nearly two thirds of the lumbar Chance-type fractures were associated with hollow viscus injuries, including six of seven children. This increased risk of Chance-type fractures and hollow viscus injuries was associated with increased use of lap-belt seat restraints in the population.

Abdominal Injuries

Biomechanics of cervical spine internal fixation.

Recent advances in the area of cervical spine internal fixation have resulted in important additions to the armamentarium of the spine surgery. However, a sophisticated knowledge of the biomechanics of these devices is important. This article discusses the biomechanics of odontoid screws, anterior cervical plates, posterior cervical plates, and posterior C1-C2 screw arthrodesis. It is hoped that this information will aid in implant selection.

Biomechanical Phenomena

Odontoid fractures treated by anterior odontoid screw fixation.

While odontoid fractures are common injuries, disagreement exists regarding treatment. Some authors claim a high rate of pseudoarthrosis and have therefore recommended early posterior fixation and fusion. This, however, results in decreased cervical rotation. Therefore, it has been recommended that a more direct approach to the fracture be taken. Results on anterior screw fixation in 14 patients are reported. The technique was found to be especially useful in multiple trauma patients, patients who refuse halo treatment, and in some nonunions.

Bone Screws

Posterior cervical arthrodesis with AO reconstruction plates and bone graft.

The efficacy of posterior arthrodesis of the cervical spine with AO reconstruction plates and autogenous bone graft was evaluated in a prospective study. The technique of surgical exposure and the application of the reconstruction plates fixed with screws to the lateral masses is described in detail. Of 30 patients with unstable cervical spines, all had solid fusions based on flexion and extension radiographs at follow-up averaging 17.8 months. No patient's neurologic function deteriorated. All incomplete spinal cord injuries improved at least one Frankel level. There were no neurologic or vascular complications. At follow-up, three patients had fusions extending one level longer than those instrumented. Three other patients had an increase in kyphosis compared with the operative reduction, which was not clinically significant. Although a single screw loosened in three other patients, none had an increased deformity, and all progressed to successful arthrodesis. This technique is particularly advantageous when spinous processes, laminas, and facets are injured or deficient, or when facet-type fusions are indicated.

Adolescent