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Biomedical subjects

D M Long

Publications and source records attributed to D M Long.

At least 109 records · Page 6Linked to original sources

Oxygen-free radicals in traumatic brain oedema.

Oxygen-free radicals have been implicated as causative factors in ischaemic and traumatic processes. Oxygen-free radical scavengers can be used potentially to treat brain oedema. We investigated the effects of superoxide dismutase and dimethylthiourea on brain oedema. Vasogenic brain oedema was produced in 44 cats by a cortical freezing lesion. Animals were separated into three groups: (1) cold-induced oedema with sacrifice at 6, 24 and 48 h; (2) cold-induced oedema with sacrifice at 6, 24 and 48 h: subgroup A was pretreated with 10,000 u./kg polyethylene glycol and superoxide dismutase; subgroup B received a bolus injection of free superoxide dismutase (4 mg/kg) and then 1 mg/kg/min for 20 min; (3) cold-induced oedema with sacrifice at 6 and 24 h: this group was pretreated with 500 mg/kg dimethylthiourea. Brain water content was measured by the specific gravity method. Detection of superoxide radicals was carried out by the direct cortical application of nitroblue tetrazolium. Free and polyethylene glycol-superoxide dismutase did not prevent the development of brain oedema, but superoxide radicals were detected in the cold lesion. Dimethylthiourea prevented the development of brain oedema in the white matter adjacent to the lesion at 6 h but not at 24 h. These findings indicate that oxygen-free radicals are generated by the brain following cold injury and the demonstration of these radicals offers an important clue in the genesis of traumatic brain oedema.

Animals↗

Hemodynamic effects of intravenous lecithin-based perfluorocarbon emulsions in dogs.

We evaluated and compared the acute hemodynamic effects of perfluorooctylbromide-100% (PFOB), a fluorocarbon emulsified in lecithin without pluronic-F68 (F68), to those of a standard iodinated contrast agent, renografin-76% (R76), and Fluosol-DA 20% (Fluosol), a fluorocarbon emulsified in part by F68. Five open chest dogs were instrumented to evaluate hemodynamic changes after iv injection of PFOB (1 ml.1 g/kg) and R76 (1 ml.0.37 g of iodine/kg). Fluosol (1 ml.0.2 g/kg) was given to two of the five dogs at the end of their study. Fluosol caused transient hemodynamic collapse in both dogs. R76 caused the known transient effect of hypotension (-15.4 +/- 3.3%) followed by hypertension (6.5 +/- 2.7%) and an increase in aortic flow (29.3 +/- 3.9% at 30 sec). PFOB caused minimal, clinically insignificant decrease in aortic flow (4 +/- 1% at 10 sec).

Animals↗

Local cerebral glucose abnormalities in mild closed head injured patients with cognitive impairments.

Mild-moderate closed head injury (CHI) can be followed by neuropsychological impairments in recent memory and attention, despite the absence of discernible structural abnormalities in a significant number of patients. To determine whether CHI may result in cerebral glucose metabolic abnormalities, we used fluorodeoxyglucose (FDG) technique with PET imaging to measure local cerebral metabolic rates for glucose (LCMRGlu) in three CHI patients and three matched normal controls. The CHI patients were between 3-12 months post-injury. All had deficits in attention and recent memory shown by neuropsychological testing. CT, MRI, EEG and drug screens were negative at the time of PET scanning. Subjects were engaged in a vigilance task throughout the initial 30 min following FDG administration. Group comparisons were made using t tests. There were no significant group differences found in global glucose metabolic rate. Nevertheless, the CHI group exhibited significantly decreased LCMRGLu in medial temporal, posterior temporal, and posterior frontal cortices, as well as in the left caudate nucleus. LCMRGlu was significantly increased, relative to controls, in anterior temporal and anterior frontal cortices. These results suggest that CHI patients can have regional glucose metabolic abnormalities, indicative of altered neuronal function, despite the absence of discernible anatomic abnormalities.

Brain↗

Placebo responses to medical device therapy for pain.

Placebo response to a functionless machine was tested in 58 patients with chronic pain. Thirteen discontinued treatment before the planned trials were complete: 5 did so because sham therapy worsened their pain. Forty-five patients completed three trials of treatment with a magnetic device, one trial of which was a sham. Thirteen percent of patients undergoing sham therapy experienced relief of pain, improved range of motion, and decrease in muscle spasm. Eleven percent of the sham trials resulted in significant increase in pain. The placebo/nocebo response to sham therapy with a device is similar to that previously reported for prolonged drug treatment, but is lower than the placebo rate for short-term medication trials.

Clinical Trials as Topic↗

Oxygen free radicals in the genesis of traumatic and peritumoral brain edema.

This study evaluates the effect of superoxide dismutase, a scavenger of oxygen free radicals, on peritumoral and cold injury edema. Vasogenic brain edema was produced in 39 cats by a standardized cortical freezing lesion. Peritumoral edema was produced by the transplantation of VX2 carcinoma cells into the brain of New Zealand White rabbits. Detection of superoxide radicals was studied by topical application of nitroblue tetrazolium to the cortical injury and by incubation of the VX2 carcinoma cells. The animals were treated with free superoxide dismutase (SOD) and polyethylene glycol superoxide dismutase (PEG-SOD). The following groups were studied: 1) control, 2) untreated tumor group, 3) tumor group treated with PEG-SOD, 4) a group treated with PEG-SOD before injury, and 5) a group treated with free SOD after injury. Brain edema was evaluated by measurement of specific gravity and planimetry study of the spread of Evans blue dye. Preliminary data indicate that superoxide radicals are present in the brain after cold injury and in the cytoplasm and nucleus of VX2 carcinoma cells. Free SOD and PEG-SOD had no beneficial effect upon the vasogenic brain edema produced in either model. It is concluded that intracellular uptake of SOD may be one of the factors necessary for an effect upon either form of edema.

Animals↗

Comparative study of different iron-chelating agents in cold-induced brain edema.

Increasing numbers of reports demonstrate the importance of iron and oxygen free radicals in brain injury and brain edema. We investigated the protective effects of three different ferric and ferrous iron-chelating agents on cold-induced brain edema. Vasogenic brain edema was produced by a cortical freezing lesion. Thirty-eight cats were separated into five groups: Group 1 (N = 8): normal control group without lesion; Group 2 (N = 8): untreated group; Group 3 (N = 8): deferoxamine (extracellular and intracellular ferric iron chelator)-treated group; Group 4 (N = 8): 2,3-dihydroxybenzoic acid (extracellular ferric iron chelator)-treated group; and Group 5 (N = 6): 2,2-bipyridine (intracellular ferrous iron chelator)-treated group. In Groups 3, 4, and 5, each agent was administered intravenously 15 minutes before lesion production and 60 minutes later. Animals in Groups 2, 3, 4, and 5 were killed 6 hours after lesion production. Brain water content in 8 sampling areas was measured by the specific gravity method. Blood-brain barrier disruption was assessed by the spread of Evans blue dye measured by planimetry. Brain water contents and Evans blue dye extravasated areas were significantly reduced in Groups 3 and 5 in comparison to Groups 2 and 4. These data suggest that both ferrous and ferric iron-chelating agents, which can penetrate the cell membrane and, presumably, act intracellularly, are effective in reducing cold-induced brain edema.

2,2'-Dipyridyl↗

Protective effect of the iron chelator deferoxamine on cold-induced brain edema.

Oxygen free radicals such as superoxide radical and iron-catalyzed hydroxyl radical generated by the superoxide system have been implicated in the genesis of brain edema. Therefore, deferoxamine (DFO), an iron chelator, could potentially be used to treat brain edema. To examine this hypothesis, vasogenic brain edema was produced in 48 cats by a cortical freezing lesion. The animals were separated into three groups: Group 1 comprised 14 cats that received no DFO and were sacrificed at 6 or 24 hours; Group 2 consisted of 12 cats that were treated with DFO (50 mg/kg/ml, intravenously) at 15 minutes before the lesion was made and 60 minutes later and were sacrificed at 6 or 24 hours; and Group 3 included 12 cats that were treated with DFO (50 mg/kg/ml, intravenously) at 15 minutes after the lesion was produced and 60 minutes later and were sacrificed at 6 or 24 hours. The effect of DFO on arterial blood pressure was also studied in the remaining 10 cats. Brain water content in eight sampling areas was measured by the specific gravity method. Blood-brain barrier disruption was assessed by spread of Evans blue dye with planimetry. Specific gravity values at 6 and 24 hours were significantly higher in Group 2 than in Group 1 animals. Areas of Evans blue dye extravasation at 6 and 24 hours were significantly reduced in Group 2 relative to Group 1. Group 3 cats showed improvement in specific gravity values and Evans blue extravasation at 6 hours, but not at 24 hours. The iron chelator DFO prevented early development of brain edema; thus, this oxygen free radical scavenger may provide a foundation for a new therapy for brain edema.

Animals↗

A century of change in neurosurgery at Johns Hopkins: 1889-1989.

Neurosurgical admissions to The Johns Hopkins Hospital during the first year of its existence, the first and last years of Harvey Cushing's practice, the last years of Walter Dandy's practice, the last years of Earl Walker's tenure, and the current neurosurgical case load are reviewed. Sixteen patients with neurosurgical problems were admitted during the first year of the hospital's existence. In the first year of Harvey Cushing's staff appointment, 38 neurosurgical patients were admitted. Infection, trauma, and trigeminal neuralgia were the most common neurosurgical problems at that time. When Harvey Cushing retired in 1912, his practice had grown to 100 operations per year. By the end of Walter Dandy's tenure, the surgical volume was much larger, more than 500 major operations per year. The development of neurosurgery virtually can be mirrored in the practice of neurosurgery under Harvey Cushing and Walter Dandy. From its humble beginnings in the treatment of trauma and infection, neurosurgery has expanded to cover all forms of intracranial disease, virtually every aspect of spinal disease, vascular disease (both intracranial and extracranial), and peripheral nerve injury. The centennial celebration at Johns Hopkins may be considered a centennial for neurosurgery. As we reflect upon our foundations, it is worthwhile to ask what changes we will contribute to the further development of neurosurgery in the next century.

Academic Medical Centers↗

Separation of craniopagus Siamese twins using cardiopulmonary bypass and hypothermic circulatory arrest.

Occipitally joined craniopagus Siamese twins were separated with the use of cardiopulmonary bypass and hypothermic circulatory arrest. The 7-month-old infants shared a large sagittal venous sinus that precluded conventional neurosurgical approach because of risk of exsanguination and air embolism. After craniotomy and preliminary exposure of the sinus, each twin underwent sternotomy and total cardiopulmonary bypass with deep hypothermia. Hypothermic circulatory arrest allowed safe division and subsequent reconstruction of the sinus remnants. Several unusual problems were encountered, including transfusion of a large blood volume from one extracorporeal circuit to the other through the common venous sinus, deleterious warming of the exposed brain during circulatory arrest, and thrombosis of both pump oxygenators. Both infants survived, although recovery was complicated in each by neurologic injury, cranial wound infection, and hydrocephalus. This case demonstrates the valuable supportive role of cardiopulmonary bypass and hypothermic circulatory arrest in the management of complex surgical problems of otherwise inoperable patients.

Brain Injuries↗

Clinical features of the failed-back syndrome.

This study comprises 78 patients who were treated for chronic back pain at a multidisciplinary, multimodal pain treatment center. These patients were selected from 494 patients examined by the authors because all of their previous medical records, operative notes, and imaging studies were available for review. The records and imaging studies were reviewed independently by a neurosurgeon and an orthopedist, and a retrospective decision was made concerning the historical and physical findings correlated with imaging studies in order to provide justification for the intervention. At the time of admission to the pain treatment center, 16 patients had no physical abnormalities that would explain their back complaint and 16 patients exhibited minor postoperative changes insufficient to cause disabling pain. Twenty-seven patients suffered from a complication of previous surgery, 13 had spondylotic disease, and in six a new diagnosis was established. Comprehensive psychiatric evaluation of the 78 patients revealed that 10 patients had a definitive psychiatric diagnosis, 34 were diagnosed as having a maladaptive personality disorder, and 34 had a normal pre-pain personality. Sixty-seven patients suffered from reactive depression. Fifty-four patients were taking medications at doses higher than usually prescribed, 58 misused narcotics, nine had drug addiction, and 54 were suffering withdrawal symptoms. Of the 78 patients, 64 underwent a total of 171 operations, an average of 2.6 per patient. The authors applied the clinical criteria approved by the American Association of Neurological Surgeons and the American Academy of Orthopedic Surgeons for selection of surgery or chemonucleolysis in the treatment of the herniated disc to these patients. Preoperative imaging studies were normal or demonstrated nonspecific degenerative disc disease in 52 patients. Twenty-six patients had a diagnosis based on radiological findings that warranted surgery. Clinical criteria justifying intervention were met in 25 patients and not met in 53. Imaging and clinical criteria for a second operation were met in 18 (40%) of the patients. After the second operation all patients met the criteria: subsequent surgery was necessary to treat effects of an earlier operation in 73%. These data indicate that many of these patients with failed-back syndrome underwent an original operation based on a persistent complaint of pain, frequently coupled with an underlying psychiatric abnormality, although they did not meet the criteria generally accepted by neurosurgeons for intervention at the time of first surgery.

Adjustment Disorders↗

Schwannoma of the medulla oblongata. Case report.

A case of intraparenchymal schwannoma of the medulla oblongata is presented. The radiographic and pathological characteristics of this rare tumor are discussed, and the world literature regarding intracerebral intraparenchymal schwannomas is reviewed. The current etiological theories of these intra-axial nerve-sheath tumors are reviewed. The importance of early identification and differentiation of these potentially curable tumors from malignant glial tumors is emphasized.

Female↗

Quantification of thermal asymmetry. Part 2: Application in low-back pain and sciatica.

Temperature differences between the lower extremities were measured using a computerized thermometric scanning system in order to compare the degree of thermal asymmetry in 144 patients with low-back pain. The patients displayed highly significant thermal asymmetries, with the involved limb being cooler (p less than 0.001). When asymmetries exceeded 1 standard deviation from the mean temperature of homologous regions measured in 90 normal control subjects, the positive predictive value of thermometry in detecting root impingement was 94.7% and the specificity was 87.5%. These values indicate that calculation of temperature asymmetry is particularly effective in evaluating reported pain in psychosocially affected patient populations in whom the chance of positive myelography or impaired root function is low. In this group of patients, thermometric study provides physicians with important information for proper decision making. The test can be performed to avoid more invasive and probably less revealing diagnostic or exploratory surgical procedures.

Adult↗