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Biomedical subjects

P R Cooper

Publications and source records attributed to P R Cooper.

At least 19 recordsLinked to original sources
PubMed2026

ARID1A Mediates ROS-Induced Osteoclast Activation in TMJ Osteoarthritis.

Excessive osteoclast activation drives rapid subchondral bone destruction, serving as a critical early-stage event precipitating temporomandibular joint osteoarthritis (TMJ-OA). Although epigenetic remodeling is widely recognized as an important interface between pathological environmental signals and genomic response, the specific epigenetic mechanisms translating TMJ-OA-associated stimulation into pathological osteoclast activation remain to be elucidated. Here, using a mechanically induced TMJ-OA mouse model, we identify aberrant reactive oxygen species (ROS) accumulation as a critical upstream driver initiating excessive osteoclast activation and subsequent joint deterioration. By integrating transcriptomic and epigenomic analyses, we delineate the chromatin remodeler AT-rich interaction domain 1A (ARID1A) as an essential oxidative stress sensor within the osteoclast lineage. Mechanistically, ROS accumulation induces ARID1A upregulation and recruitment to the Src enhancer, transcriptionally activating Src and amplifying PI3K-AKT signaling to drive pathological osteoclastogenesis. Conditional knockout of Arid1a in myeloid cells effectively abrogates subchondral bone loss and cartilage destruction in TMJ-OA. Translating these mechanistic insights, we engineered an ROS-responsive, osteoclast-targeting hydrogel for the on-demand delivery of an ARID1A-dependent canonical BRG1/BRM-associated factor complex inhibitor, which successfully alleviates TMJ-OA progression. Our findings establish the epigenetic response to ROS accumulation as a key pathogenic mechanism in TMJ-OA and highlight ARID1A as a promising therapeutic target for early disease intervention.

biomaterial(s)↗
PubMed1979

Computed tomography findings in ruptured arteriovenous malformations of the corpus callosum.

Computed tomography (CT) is of proven value in the evaluation and localization of intracranial hemorrhage. The recognition of various patterns of subarachnoid, intracerebral, and intraventricular hemorrhage is necessary in order to provide accurate localization and to predict probable etiology of the bleed. We present three cases with angiographically proven ruptured arteriovenous malformations involving the midline of the corpus callosum. The clinical presentation and CT findings are discussed. We believe this represents a distinctive pattern of hemorrhage specific for this entity.

Adult↗
PubMed1979

Enhancement of experimental cerebral edema after decompressive craniectomy: implications for the management of severe head injuries.

Decompressive craniectomy has been advocated as a treatment for the cerebral edema associated with massive head injury. Although craniectomy has been successful in lowering intracranial pressure after head injury, a comparison of computerized tomographic scans of comparable patients with traumatic brain edema treated by medical means or decompressive craniectomy showed that bony decompression resulted in apparent exacerbation of edema. To investigate the possibility of enhancement of brain edema by craniectomy, we produced standardized cold lesions in the brains of 10 dogs. Five animals served as controls. In the other 5 animals we performed large decompressive craniectomies after lesioning. Physiological parameters were comparable in both groups. The dogs were killed 8 hours after lesioning. After fixation, their brains were cut into 1-mm-thick slices. We used an image analysis facility built around a PDP 11/105 computer to measure the volume of edema as outlined by Evans blue staining. The mean volume of the brain edema in the control animals was 0.27 +/- 0.19 ml. Mean edema volume was over 7 times greater in craniectomized animals (1.96 +/- 1.89 ml). This difference is statistically significant (p less than 0.05). The driving force for the formation of edema fluid is the difference between intravascular and interstitial presssure. Decompression of the brain by bone removal probably results in a reduction of interstitial fluid pressure and edema enhancement. The clinical literature contains no evidence that craniectomy decreases the morbidity or mortality of human head injury. In view of our experimental findings, this is not surprising. Indeed, pathological evidence indicates that severe edema (such as that accentuated by craniectomy) may produce permanent changes in the neuropil.

Animals↗
PubMed1979

Computerized tomographic scan and gunshot wounds of the head: indications and radiographic findings.

The authors document their experience with the computerized tomographic (CT) scanner for evaluating gunshot wounds of the head. Only those patients who were considered to be operative candidates and who were neurologically stable were scanned. In the postoperative period, patients who were not scanned preoperatively and those whose condition did not improve were also scanned. In the preoperative period the CT scanner is useful for identifying and localizing missile tracks, bony and metallic fragments, intra- and extraparenchymal hematomas, intracranial air, and brain swelling. In the postoperative period the CT scanner may demonstrate retained bone fragments, edema, brain abscess, and intracranial air. The limitations of the CT scan in evaluating gunshot wounds include an inability to define vascular lesions suchas traumatic aneurysms and post-traumatic spasm. Metallic scatter from missile fragments may render certain CT cuts uninterpretable. In addition, the CT scan may appear minimally abnormal in spite of immediate and irreversible injury caused by a shock wave transmitted to brain stem structures. The CT scanner has superceded angiography as a diagnostic tool for evaluating gunshot wounds of the head because it is noninvasive and rapid, allows visualization of the entire head, can resolve very small lesions that produce little or no mass effect, can help to determine the nature of intracranial lesions and may quantitate the amount of hemorrhage and edema. Because it enables physicians to visualize intracranial structures in three dimensions, the CT scan may precisely define missile tracks and contiguous lesions in a manner not heretofore possible with other diagnostic modalities. Thus, it is invaluable for the rational planning of surgical therapy.

Brain Injuries↗
PubMed1979

Cerebrospinal fluid dynamics in patients with pseudotumor cerebri.

CSF dynamics were determined as a function of intracranial pressure in patients with pseudotumor cerebri. Servocontrolled variable rate lumbar infusions were used to determine net CSF-absorptive capacities and resting pressures in 10 patients; serial studies were done in 5 of the patients. Nearly all of the patients had abnormally low CSF-absorptive capacities. On the other hand, marked elevations in resting pressure were not a constant feature of the disease. Concurrent changes in the cerebrovascular bed could introduce errors into this manometric determination of CSF dynamics; the significance of this potential artifact is examined. The results of this study suggest that the CSF compartment may be of etiological importance in the pathophysiology of pseudotumor cerebri.

Adolescent↗
PubMed1979

Serial computerized tomographic scanning and the prognosis of severe head injury.

Serial (two or three) computerized tomographic (CT) scans were performed on a series of 58 patients with severe head injury. The protocol called for scans to be done upon admission and on Days 3 and 7 after injury. New lesions (i.e., lesions not visualized on the initial CT scans but appearing on subsequent scans) were a frequent finding, occurring in over half of all patients. For the purposes of this study a new lesion was classified as edema involving two or more lobes, extra-axial hematoma, parenchymal hemorrhage, or infarction. Significant correlation was found between good outcome and the absence of new lesions and between bad outcome and the development of new lesions (p less than 0.001). Several patients did well in spite of the development of new lesions, but these patients were unique in that most had small, unilateral parenchymal hematomas located at or near the frontal or temporal poles. In most cases, patients who did poorly in spite of not developing new lesions had severe injuried visualized on their initial scans (massive intracerebral hematoma, hemorrhage of the corpus callosum) or succumbed to medical complications. The pertinent literature is reviewed, and other CT findings associated with a poor prognosis are noted. The authors suggest that serial CT scanning may be used to make prognostic assessments in severely head-injured patients and may be of value in increasing the confidence in and accuracy of assessments made on clinical grounds alone. (Neurosurgery, 5: 566--569, 1979).

Brain Edema↗
PubMed1979

Chronic monitoring of intracranial pressure using an in vivo calibrating sensor: experience in patients with pseudotumor cerebri.

A number of reliable methods are available for the short term monitoring of intracranial pressure (ICP). However, the danger of infection and the need for external connections make the use of these methods for extended periods inappropriate. Most previously described devices for chronic monitoring of ICP are of limited value because of uncertain drift from zero-point readings. The Hittman-Meyer ICP sensor approaches the ideal for a long term monitoring device. It is fully implantable and is accurate over a wide range of pressures and for extended periods. It is designed so that in vivo calibration may be performed in a noninvasive fashion. We report the use of this device in eight patients with pseudomotor cerebri. It has functioned accurately for periods ranging up to 14 months after implantation and has proven to be a valuable aid in the management of these patients. (Neurosurgery, 5: 666-670, 1979).

Adult↗
PubMed1979

Halo immobilization of cervical spine fractures. Indications and results.

Thirty-three patients with a spectrum of cervical spine fractures or subluxations were treated with immobilization by a halo apparatus. All spines were assumed to be unstable because of the nature of the fracture or because of a subluxation noted on spine films. Treatment consisted of immobilization and fracture reduction followed by application of a halo plaster cast or molded halo plastic vest. Patient acceptance was high. Complications were few and minor. No patient experienced neurological deterioration during treatment. Reduction was well maintained during an average halo immobilization period of over 3 months. Use of the halo resulted in healing of bone and ligament and restoration of stability in 85% of the patients. Halo immobilization was efficacious in the treatment of odontoid and hangman's fractures as well as complex fractures involving multiple areas of a single vertebra. It was also used successfully as an adjunct to posterior cervical fusion. Although several patients with subluxations or angulation without bone injury were treated successfully, two of the four therapy failures occurred in this group of patients, and the halo must be used with caution in this clinical setting. Contraindications to the use of the halo include complete cervical spinal cord injury with anesthetic skin, tomographic and/or myelographic evidence of disc or bone within the spinal canal, and unsatisfactorily reduced subluxations. The halo has provided more effective and reliable immobilization than other orthoses. It is an acceptable alternative to cervical fusion for the achievement of stability in a wide variety of cervical spine fractures and dislocations avoiding both the short-term and perhaps long-term complications of spinal fusion.

Adolescent↗
PubMed1979

Dexamethasone and severe head injury. A prospective double-blind study.

A prospective double-blind study of the effects of dexamethasone administration on the outcome of patients with severe head injuries was performed. Patients were stratified for severity of neurological injury and were treated with placebo, low-dose dexamethasone (16 mg/day), or high-dose dexamethasone (96 mg/day) for a period of 6 days. Outcome was evaluated at 6 months following injury. Of the 76 patients available for analysis, a good outcome was achieved in 37% of placebo-treated patients, 44% of low-dose-treated patients, and 29% of high-dose-treated patients. These differences are not statistically significant. Similarly dexamethasone administration had no statistically significant effect on intracranial pressure patterns or serial neurological examinations during hospitalization. Gastrointestinal bleeding occurred in only one patient. Good outcome was associated with age under 10 years, lighter depth of coma on admission, and the preservation of brain-stem reflexes upon admission. A recalculation of data in previous clinical series purporting to show an improvement in outcome as a result of corticosteroid therapy shows no significant difference in outcome when steroid- and placebo-treated patients are compared. In our series, 90% of all deaths were caused by recurrent intracranial hematomas, medical complications, or diffuse brain injuries with parenchymal hemorrhage and tissue disruption -- causes of death which cannot be affected by corticosteroid therapy. The study suggests that dexamethasone in either high or low dosages has no significant effect on morbidity and mortality following severe head injury.

Adolescent↗
PubMed1978

Neurodiagnostic studies and the management of head injury.

The rational management of patients with head injury calls for the closest cooperation between the radiologist and neurosurgeon. Until the last three to four years, cerebral angiography had been considered the diagnostic procedure of choice for the management of patients with suspected traumatically induced intracranial mass lesions. Experience with CT scanning now indicates that for a number of reasons this procedure is to be preferred in the diagnosis of head injuries. It is more rapid than angiography, routinely visualizes the entire brain, is noninvasive, resolves lesions that are much smaller than any visualized by angiography and defines the density and thus the nature of traumatic lesions in a manner not possible with previously employed techniques. Using CT scanning in a sequential fashion we have routinely been able to visualize the appearance of new lesions in the post-traumatic period and have as well, been able to develop insights into the temporal appearance and disappearance of white matter edema as measured by Hounsfield numbers. In the late post-traumatic period, it has been valuable in defining hydrocephalus, porencephaly and other post-traumatic lesions that have a significant bearing on both therapy and prognosis.

Aged↗
PubMed1978

The influence of thin-section tomography on the treatment of cervical spine injuries.

A study was performed to determine the influence of routine thin-section tomography on subsequent treatment of the patient with acute trauma to the cervical spine. Of 79 such patients who underwent tomography over a 14-month period, 55 had suspicious indirect findings on the radiograph and 25% of these were shown to have fractures, while 67% of the patients without radiographic abnormalities who presented with a neurological deficit also demonstrated fractures on tomography. Of the patients who were shown to have fractures prior to tomography, 54% had more extensive injury than originally suspected. In nearly 18% of patients, the mode of therapy was changed significantly after tomographic evaluation. Indications for tomography are discussed and specific recommendations for systematic radiographic evaluation of cervical spine injuries are presented.

Adolescent↗
PubMed1977

Disc space infections in children.

Intractable low back pain in children is often due to disc space infections. The clinical presentation, diagnostic workup, and treatment of four cases are presented. Symptoms often occur well before radiographic findings are evident. The diagnosis can only be made by a high degree of suspicion and repeated X-rays. Antecedent causes, such as urinary infection or intravenous administration of narcotics were lacking in this group. Fever or a preceding febrile illness was often, but not invariably, present. Percutaneous biopsies were not usually helpful. Myelography in each instance was normal. Bed rest reduced but did not alleviate the back pain. The institution of appropriate antibiotic therapy resulted in a prompt diminution of pain.

Adolescent↗
PubMed1977

The investigation of epiphora.

The investigation and management of a patient with a tearing problem demands evaluation of the lacrimal passages by syringing and intubation macrodacryocystography with subtraction prints. Data regarding function can be provided by a nuclear lacrimal scan and computer assisted scintillography. We describe our experience with 163 patients.

Dacryocystorhinostomy↗
PubMed1977

A pre-formed methyl methacrylate cranioplasty.

The use of a pre-formed methyl methacrylate cranioplasty prosthesis reinforced with stainless steel wire is described. The prosthesis is non-reactive, virtually unbreakable, and undentable. Pre-forming of the prosthesis in the dental laboratory using a mold of the patient's bony defect as a model saves considerable operating time, and when employed for a large cranial defect the three dimensional cosmetic effect is superior to intra-operatively fashioned prostheses.

Biocompatible Materials↗