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Biomedical subjects

J Hazel

Publications and source records attributed to J Hazel.

14 recordsLinked to original sources

Low-grade pure and mixed cerebral astrocytomas treated in the CT scan era.

From 1974 to 1992, 63 patients diagnosed with low-grade pure or mixed oligo-astrocytoma were seen and treated at our institution. All patients underwent CT scan pre-operatively. There were 20 female and 43 males ranging in age from 12 to 73 years (median age of 33 years). 15 patients had a stereotactic biopsy as the only surgical procedure. 34 had a partial tumor resection and 14 a gross total tumor resection. 43 patients were treated with post-operative radiotherapy whereas 20 patients underwent surgery only as part of the initial management. 50 to 60 Gy (median 59.4 Gy) were given with daily fractions of 1.8 to 2 GY. Tumor volume ranged from 3.4 to 441 cm3. Median tumor volume was larger for radiotherapy treated patients. Median follow-up was 54 months (range of 4 to 240 months). The overall 10 and 15 actuarial survival rates were 37% and 25% respectively. The 5 years survival rate for patients treated at initial diagnosis with surgery alone was 66% and it was 67.3% for patients treated with radiation therapy (P = NS). Prognostic factors having independent significant impact on survival were: extent of surgery, age gender and tumor volume. As well, survival for patients with low-grade astrocytoma in the CT scan era appears to be improved compared to historical controls in the literature.

Adolescent

Cholesterol levels explain inverse compensation of membrane order in brush border but not homeoviscous adaptation in basolateral membranes from the intestinal epithelia of rainbow trout

The role of cholesterol in the thermal adaptation of biological membranes is explored. Physical and chemical responses of membranes to acclimation temperature were evaluated using plasma membrane domains (basolateral and brush border) prepared from intestinal epithelia of 5- and 20 °C-acclimated rainbow trout (Oncorhynchus mykiss). Basolateral membranes (BLMs) exhibit perfect homeoviscous efficacy (indicated by fluorescence depolarization using 1,6-diphenyl-1,3,5-hexatriene), although cholesterol content does not change with acclimation temperature (molar ratios of cholesterol to phospholipid are 0.23± 0.01 from 5 °C-acclimated fish and 0.25±0.02 from 20°C-acclimated fish; mean ± s.e.m.). Reductions (greater than 30 %) in each of the two major saturated fatty acids (16:0 and 18:0), and a 42 % increase in the polyunsaturate 22:6 (n-3) are found in BLMs from fish acclimated to 5 °C compared with membranes from warm-acclimated animals, suggesting that the phospholipid acyl chain composition determines the physical properties of BLMs. In marked contrast, brush-border membranes (BBMs) display opposite trends. BBMs from 5 °C-acclimated fish are more ordered than BBMs from 20 °C-acclimated fish (inverse compensation). Cholesterol content expressed relative to protein or relative to total polar lipid (phospholipid plus glycolipid) is significantly higher in cold- than in warm-acclimated fish, and nearly so (P=0.15) relative to phospholipid (0.31±0.03 in 5 °C-acclimated animals and 0.25±0.02 in 20 °C-acclimated animals). Only minor changes in the acyl composition of BBMs are induced by temperature acclimation. These results suggest that bile, a constituent of the apical microenvironment, may impose unusual requirements for membrane order and/or stability in the brush border.

Journal Article

Fractionated stereotactic radiotherapy for intracranial neoplasms.

Fractionated stereotactic radiotherapy is a method which attempts to combine the radiobiological advantages offered by dose fractionation with a technique for focal delivery of radiation. At McGill University, fractionated stereotactic radiotherapy is given with a linear accelerator-based dynamic stereotactic radiosurgery unit. The first treatment is given using the stereotactic frame for target localization and head immobilization. Subsequent treatments are given using skin tattoos and laser alignment for target placement within the isocenter of the linear accelerator, and a modified portable halo-ring device is used for skull immobilization. Typically, a marginal dose of 42 Gy was prescribed at the margins of the lesion, divided in 6 fractions and given over a 2-week period. We report the pathological profile and treatment results in a series of 21 patients with a variety of intracranial tumors, treated in this manner between May 1987 and April 1990. Fractionated stereotactic radiotherapy appears to be a worthwhile procedure for the treatment of well-selected patients with intracranial neoplasms.

Adult

Accelerated fractionation for high-grade cerebral astrocytomas. Preliminary treatment results.

A Phase I/II accelerated fractionation study for high-grade cerebral astrocytomas began in October 1987. Forty-two patients, 25 men and 17 women, were entered in the study. Median age was 58.5 years of age (range, 32 to 78 years). Performance status was 0, 1, 2, and 3 on Eastern Cooperative Oncology Group (ECOG) scale for 13, 19, 9, and 1 patients, respectively. Thirty-six patients had undergone partial resection, and six had stereotactic biopsy only. All patients had histologically proven astrocytomas (6 Grade 3, and 36 Grade 4). Treatment consisted of radiation therapy doses of 4400 cGy in 22 daily fractions to the whole brain plus a boost of 1600 cGy in 8 fractions given concomitantly with the last 8 whole-brain treatments using a twice daily schedule with an interfraction interval of 8 hours. Median survival time was 57 weeks from the date of starting irradiation. Survival was 50% and 28% at 1 and 2 years, respectively. Alopecia and scalp erythema were seen in all patients; nine patients had localized areas of moist desquamation in the retroauricular region. Decreased hearing and serous otitis media were seen in five patients within 1 to 2 months from the end of treatment. Increasing somnolence was marked in eight patients with progressive deterioration of performance status; computerized axial tomography (CAT) scan studies in all eight patients showed evidence of disease recurrence with associated brain edema and mass effect. Three patients had a second resection for a recurrent tumor with no evidence of brain necrosis at craniotomy. To date, the accelerated fractionation schedule appears to be well tolerated with valuable shortening of overall treatment time. The preliminary results are encouraging, and longer follow-up time is required to evaluate tumor control and toxicity.

Adult

Dynamic stereotactic radiosurgery in arteriovenous malformation. Preliminary treatment results.

From December 1986 through August 1988, 25 patients with intracranial arteriovenous malformations underwent radiosurgery with the dynamic stereotactic irradiation technique. The prescribed dose at isocenter ranged from 50 Gy to 55 Gy, given as a single fraction in 92% of the patients. Field sizes, defined at the 90% isodose surface, varied from 5 mm to 25 mm and were chosen in order to deliver 20 to 25 Gy at the periphery of the malformation. To date, 14 angiographic studies were repeated at 1 year posttreatment. In six patients (43%) a complete obliteration of the lesion was achieved. Late side effects were observed in three patients. Our initial analysis, at 1 year posttreatment, suggests that our results are comparable with those previously reported for other radiosurgical techniques. The linac-based dynamic stereotactic technique appears to be a valid alternative to radiosurgery with the Gamma unit or with heavy-charged particle beams.

Adolescent

Dynamic stereotactic radiosurgery.

Two radiosurgical procedures using a stereotactic frame and a linear accelerator X ray beam with a circular field diameter between 0.5 and 3 cm are presented. One technique is based on a single plane rotation (single plane radiosurgery) whereas the other uses simultaneous and continuous motions of both the gantry (approximately 360 degrees) and couch (approximately 180 degrees) during the radiosurgical procedure (dynamic radiosurgery). The dose, typically a few thousand cGy, is prescribed to the 90% isodose line which just covers the target volume. The dose fall-off outside the spherical target volume is considerably sharper for the dynamic rotation than for the single plane rotation, and is comparable to the dose fall-off obtained with the two presently known dedicated radiosurgical techniques: one based on focused cobalt beams and the other on proton beams. The dose fall-off in the dynamic radiosurgery discussed here is also comparable to that of previously described linear accelerator based multiple converging are techniques, making the dynamic radiosurgery an attractive alternative to presently known radiosurgical procedures. The radiation beam parameters are discussed and the stereotactic frame described. The dose distributions for both radiosurgical techniques are calculated in a single plane and then corrected for the attenuation effects in the stereotactic frame (approximately 2%) and for the effects of the dynamic rotation (approximately 2%). The skin doses are 0.7% and 2%, and the lens doses, if the beam passes through the eyes, are 2.5% and 3.5% for the dynamic rotation and single plane rotation, respectively. The scatter and leakage dose for the radiosurgical procedures is typically 0.2% to the patient's thyroid, 0.06% to the breast, and 0.02% to the gonads.

Brain Diseases

Physical aspects of dynamic stereotactic radiosurgery.

Dynamic stereotactic radiosurgery is a radiosurgical technique based on a medium-energy isocentric linear accelerator and a stereotactic frame. The technique uses concurrent and continuous rotations of both the gantry (300 degrees, from 30 to 330 degrees) and the couch (150 degrees, from 75 to -75 degrees). It gives a uniform dose (+/- 5%) within the target volume and dose fall-offs outside the target volume comparable to those obtained from presently known radiosurgical techniques.

Humans

Steroid structure and function:I. Conformational transmission in 17alpha-acetoxy progesterone.

The molecular conformation of 17alpha-acetoxy progesterone has been determined crystallographically and is compared with that of progesterone. The 17alpha-acetate substituent restricts the flexibility of the progesterone side chain, strains bond lengths in the C- and D-rings, and has long range effects on the A-ring conformation. The A-ring adopts a perfect sofa conformation similar to that observed in one conformational isomer of progesterone. Consequently this progesterone isomer is proposed to be that best suited to binding in the rabbit and human uterus.

Chemical Phenomena

Molecular conformation of ammonium 8-anilino-1-naphthalenesulfonate hemihydrate. A fluorescent probe for thyroxine binding to thyroxine binding globulin.

The crystal and molecular structure of the ammonium hemihydrate salt of the fluorescent dye, 8-anilino-1-naphthalenesulfonic acid (ANS), has been determined. There are two conformationally distinct molecules in the triclinic P1 lattice. The anilino nitrogen of one molecule has slightly distorted planar geometry, and the overall conformation of the molecule is similar to that observed for the potassium salt of the fluorescent dye 2-p-toluidinyl-6-naphthalenesulfonic acid (TNS). The anilino nitrogen of the other molecule has slightly distorted tetrahedral geometry and the overall conformation of the molecule is similar to that observed for the thyroid hormones T3 and T4. The observation of two distinct conformational modifications of ANS in this crystal structure determination has shed light on the conformational flexibility of the ANS molecule itself and on the mode by which its acts as a competitive inhibitor in thyroid hormone transport proteins and as a signal for hydrophobic areas in macromolecular systems.

Anilino Naphthalenesulfonates

Molecular structure of thyroxine analogues. Crystal structure of 3,5,3'-triiodothyroacetic and 3,5,3',5'-tetraoiodothyroacetic acid N-diethanolamine (1:1) complexes.

Crystallographic data demonstrated that conformations of thyroid hormones and their derivatives in which the phenyl rings are either skewed (phi,phi'; +/-90,0 degrees) or twist-skewed (phi,phi'; +/-108, +/-28 degrees) are energetically favored. Acetic acid metabolites are consistently observed in the skewed conformation whereas their parent hormones are observed in the twist-skewed conformation. These preferences are manifestations of long-range conformational transmission and together with plasma protein binding data may indicate a site-specific preference for the skewed vs. twist-skewed conformation. These findings result in part from the crystal structure determinations of the N-diethanolamine (1:1) complexes of the active thyroxine metabolites 3,5,3'-triiodothyroacetic acid (T3AA) and 3,5,3'5'-tetraiodothyroacetic acid (T4AA) which are reported here. The conformation of the 3'-iodine in the hypocholestermic agent T3AA is distal, the biologically preferred conformation, and the overall conformation of T3AA is transoid, while that of T4AA is cisoid.

Chemical Phenomena