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Biomedical subjects

J McKean

Publications and source records attributed to J McKean.

7 recordsLinked to original sources

Pediatric temporal lobectomy for epilepsy.

BACKGROUND: Temporal lobectomy in adults is an accepted form of treatment for patients with intractable complex partial seizures. There have been few long-term studies of children undergoing temporal lobectomy for epilepsy. METHODS: We reviewed the pediatric cases of temporal lobectomy for intractable epilepsy performed by the Comprehensive Epilepsy Program at the University of Alberta Hospitals between 1988 and 2000. All patients had preoperative and postoperative clinical evaluations, seizure charts, drug levels, EEG, CT/MRI, long-term video EEG monitoring and neuropsychological testing. The patients were reassessed at 6 weeks, 6 months and 1 year postoperatively, then yearly. The duration of follow up was 1-10 years (mean 5 years). RESULTS: Forty-two patients were studied (25 males and 17 females). Age at surgery ranged from 18 months to 16 years. The interictal EEG was abnormal in 38 of the 42 patients. Twenty-two patients had focal epileptic discharge and 1 had generalized epileptic discharge. Focal slowing was seen in 9 patients and diffuse slowing in 5 patients. CT scan was abnormal in 17 of 39 patients and normal in 22 of 39. MRI was abnormal in 34 of 42 patients and normal in 8 of 42. Pathology included brain tumors in 14 patients, mesial temporal sclerosis in 8, focal cortical dysplasia in 4, tuberous sclerosis in 4, dual pathology in 4, porencephalic cyst in 1 and normal pathology or gliosis in 6. Thirty-three of 42 patients (78%) were seizure-free following surgery and an additional 5 (12%) had a decrease in seizure frequency. Three patients had complications, but there were no deaths. CONCLUSION: Temporal lobectomy is a safe and effective treatment for children with intractable complex partial seizures. Seventy-eight percent of patients are seizure-free following the surgery and there are few complications. MRI is superior to CT scan for detection of temporal lobe pathology yet failed to detect abnormalities in some patients. The most common pathologies found were brain tumors, mesial temporal sclerosis and developmental lesions. In addition to seizure control, many patients experienced improvement in cognitive and psychosocial function following surgery.

Adolescent↗

Ligament tissue engineering using synthetic biodegradable fiber scaffolds.

Tissue engineering offers the possibility of replacing damaged human ligaments with engineered ligament tissues. Hence, we attempted to culture in vitro ligament tissues by seeding human anterior cruciate ligament (ACL) and medial collateral ligament (MCL) cells onto synthetic biodegradable polymer fiber scaffolds. The ACL and MCL cells readily attached to the scaffold fibers. These cells and their secreted matrix soon surrounded the scaffold fibers and bridged the gaps in between. Beginning at 2 weeks, portions of the scaffolds were completely filled with tissue matrix. By 5 weeks, the scaffolds became single bundles of tissue. Thus the cell/fiber system appears to be a viable system for culturing ligament tissues. Additionally, cell proliferation under mechanical and biochemical stimuli was studied for up to 4 days. Whereas mechanical stimulus and transforming growth factor enhanced proliferation, inflammatory agents (lipopolysaccharide and complement C5a) had a negative effect. This work can thus contribute to a sound strategy for culturing replacement ligament tissues in vitro.

Anterior Cruciate Ligament↗

Dendritic alterations in cortical pyramidal cells in the sparse fur mouse.

Ornithine carbamoyltransferase deficiency, an X-linked trait, leads to toxic hyperammonemia in sparse fur (spf/Y) mice. Quantitative analysis of the basilar dendritic tree of layer V pyramidal cells in frontoparietal cortex stained by the Golgi Kopsch method revealed a significant decrease in both the complexity of the dendritic arbor and in dendritic terminal spine density (60%) in spf/Y mice compared with controls. Such reductions may contribute to behavioral dysfunction observed in spf/Y mice.

Animals↗

Contributions of beta-adrenoceptor subtypes to responses to isoprenaline in rat isolated distal colon.

The effects of the non-selective beta-adrenoceptor antagonist propranolol and the beta 1- and beta 2-adrenoceptor-selective antagonists, respectively CGP 20712A (((+/-)-[2-(3-carbamoyl-4-hydroxyphenoxy)-ethylamino]-3-[4-(1-meth yl-4- trifluoromethyl-2-imidazolyl)-phenoxy]-2-propanol hydrochloride)) and ICI 118,551 ((erythro(+/-)-1-(7-methylindan-4-yloxy)-3-isopropylamino butan-2-ol- hydrochloride)), on isoprenaline-induced inhibition of methacholine contractions in rat distal colon were investigated to determine the contributions of beta-adrenoceptor subtypes to relaxation of smooth muscle. Longitudinal segments of rat distal colon were suspended in Krebs solution at 37 degrees C for isometric recording. The Krebs solution contained EDTA (30 microM), ascorbic acid (30 microM) and prazosin (0.1 microM) and was gassed with 95% O2-5% CO2. Isoprenaline produced a concentration-dependent inhibition of methacholine-induced contractions. Propranolol produced a small (4-6-fold) significant shift of the isoprenaline concentration-response curve at 0.003-0.01 microM. Larger shifts were produced by 0.3 microM (13-fold) and 1 microM (20-fold). CGP 20712A produced a small (3-5-fold) significant shift at 0.03-1 microM. ICI 118,551 produced small non-significant shifts (2-3-fold) at 0.03-1 microM. A combination of ICI 118,551 (0.3 microM) and CGP 20712A (0.1 microM) produced a 13-fold shift, a significantly greater shift than expected from the individual shifts. The shift produced by the combination of antagonists was slightly less than that produced by 1 microM propranolol (20-fold).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Photoradiation therapy: current status and applications in the treatment of brain tumors.

Photoradiation therapy is achieved when a photosensitizing drug is activated by light to form products that are lethal to tumor cells. The most commonly used drug is hematoporphyrin derivative, which is preferentially taken up and retained by malignant tissue. Photoactivation is usually produced by using a dye laser tuned at 630 nm (red light). The primary mechanism of neoplastic cell damage in photoradiation therapy involves the production of free radicals formed during illumination of hematoporphyrin derivative by light of this wavelength. The treatment would seem to damage first the tumor cell membrane, then the cytoplasmic inclusions, and finally the nucleus. Photoradiation therapy has been quite effective in the treatment of superficial malignancies, especially in skin, breast, eye, bladder, bronchus, and stomach. Experience with brain tumors is still limited. Important unresolved problems in the application of photoradiation therapy to gliomas include relative uptake of hematoporphyrin derivative into the tumor, limited light penetration of the tissue, local heating, and damage induced in normal brain by photoradiation therapy.

Brain Neoplasms↗

Photoradiation therapy of 9L-gliosarcoma in rats: hematoporphyrin derivative (types I and II) followed by laser energy.

Suspensions of 9L-gliosarcoma cells were inoculated into the brain or flank of rats and photoradiation therapy (PRT) was applied to the resulting tumors. The PRT consisted of hematoporphyrin derivative (HpD), type I or II, followed by single-fiber laser energy 24, 48, or 72 h later. Necrotic foci in brain tumors were most numerous following laser exposure 24 h after HpD; they were more than twice as common, and with less damage to healthy tissue, after HpD II than after HpD I with the same laser dose. Neither lifespan nor the final weight of brain tumor was affected by the type of HpD or whether PRT was applied once or twice. In rats with flank tumor, multiple PRT (up to X 4) did not delay tumor growth; also, 11 of 12 PRT-treated flank tumors grew after implantation at various sites in healthy rats. We conclude that HpD II is a more effective photosensitizer than HpD I. However, the value of PRT will be limited until a lethal dose of laser energy can be delivered throughout a tumor without destroying vital healthy tissue.

Animals↗

Effects of photoradiation therapy on normal rat brain.

Laser photoradiation of the brain via an optical fiber positioned 5 mm above a burr hole was performed after the injection of hematoporphyrin derivative (HpD) in 33 normal rats and 6 rats with an intracerebral glioma. Normal rats received HpD, 5 or 10 mg/kg of body weight, followed by laser exposure at various doses or were exposed to a fixed laser dose after the administration of HpD, 2.5 to 20 mg/kg. One control group received neither HpD nor laser energy, and another was exposed to laser energy only. The 6 rats bearing an intracranial 9L glioma were treated with HpD, 5 mg/kg, followed by laser exposure at various high doses. The temperature in the cortex or tumor was measured with a probe during laser exposure. The rats were killed 72 hours after photoradiation, and the extent of necrosis of cerebral tissue was measured microscopically. In the normal rats, the extent of brain damage correlated with increases in the dose of both the laser and the HpD. In all 6 glioma-bearing rats, the high laser doses produced some focal necrosis in the tumors but also damaged adjacent normal brain tissue. We conclude that damage to normal brain tissue may be a significant complication of high dose photoradiation therapy for intracranial tumors.

Animals↗