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Biomedical subjects

S Packer

Publications and source records attributed to S Packer.

At least 55 records · Page 3Linked to original sources

Sympathetic stimulation and hypertension in the pyridoxine-deficient adult rat.

Pyridoxal phosphate is the coenzyme of various decarboxylases involved in the formation of monoamine neurotransmitters such as gamma-aminobutyric acid, serotonin, dopamine, and norepinephrine. Adult male Sprague-Dawley rats placed on a pyridoxine-deficient diet for 8 weeks showed significant hypertension compared with pyridoxine-supplemented controls. Hypothalamic contents of pyridoxal phosphate, gamma-aminobutyric acid, and serotonin in the pyridoxine-deficient rats were significantly lower than those in pyridoxine-supplemented controls. Hypertension was associated with sympathetic stimulation. Treatment of pyridoxine-deficient rats with a single dose of pyridoxine (10 mg/kg body weight) reversed the blood pressure to normal levels within 24 hours, with concomitant restorations of hypothalamic serotonin and gamma-aminobutyric acid as well as the return of plasma norepinephrine and epinephrine to normal levels. Also, pyridoxine treatment reversed the hypothalamic hypothyroidism observed in pyridoxine-deficient rats. These results indicate an association between pyridoxine deficiency and sympathetic stimulation leading to hypertension.

Animals↗

Iodine-125 radiation of posterior uveal melanoma.

Twenty-eight cases of posterior choroidal melanoma were treated with iodine-125 in gold eye plaques. Eleven cases were located within 3.0 mm of the optic nerve (group A), nine were within 3.0 mm of the fovea (group B), and eight were within 3.0 mm of the optic nerve and fovea (group C). The mean follow-up of group A was 46.3 months; group B, 25.5 months; and group C, 42.7 months. Complications included macular edema, cataract and tumor growth. Visual acuity remained within two lines of that tested preoperatively for 4 of 11 patients in group A, 4 of 9 in group B, and 5 of 8 in group C. These results with iodine-125 suggest it as an appropriate treatment for patients with choroidal melanoma located near optic nerve and/or macula.

Cataract↗

Samarium-145: a new brachytherapy source.

A new radiation source has been produced for brachytherapy, with radiation energies slightly above those of 125I, and a T1/2 of 340 d. This source, 145Sm, is produced by neutron irradiation of 144Sm (96.5% enriched). Decay is by electron capture with 140 K x-rays per 100 disintegrations in the energy region between 38-45 keV, plus 13 gamma-rays at 61 keV. These sources are encapsulated in Ti tubes, approximately 0.8 mm X 4.5 mm, and have been developed for temporary implantation in brain and ocular tumours. The 38-61 keV photons should make such sources easy to shield, while providing a dose distribution from source arrays somewhat more homogeneous than that from 125I. In addition, the 340 d half life of 145Sm permits its use for times significantly longer than that of 60 d 125I. While the 145Sm sources have been designed primarily for implantation in a brain tumour, they should be useful for almost any conventional brachytherapy application.

Brachytherapy↗

Resident training in chronic care and rehabilitation.

Although the Royal College requires that residents receive training in the rehabilitation of psychiatric patients, much leeway has been given to individual departments of psychiatry as to program content. This has often led to inadequate training since residents may be exposed to chronic patients without any training in rehabilitation. In order to meet this deficiency McGill University and the University of Toronto have developed specific program requirements. These are described below.

Canada↗

New techniques for iodine-125 radiotherapy of intraocular tumors.

Low-energy radiation sources, such as iodine-125, are suitable for treating choroidal melanoma because of their physical characteristics. Iodine-125 emits x-rays and gamma-rays between 27 and 35 keV. Gold plaques can direct radiation toward the tumor and minimize radiation to normal ocular structures. Effective treatment requires the cooperation of the ophthalmologist, radiotherapist, and radiation physicist. The preparation of the radioactive plaque and methods for its accurate surgical placement are detailed.

Choroid Neoplasms↗

Scleral hyperplasia induced by heat.

We evaluated low-level heating as a stimulus to induce hyperplasia of normal rabbit sclera. Heat treatments were administered by placing an etched-element heater on bare sclera. Contact thermotherapy with a conductive device provided a favorable dose distribution for local scleral heating. A purely conductive heat source was selected to minimize intraocular heat penetration and to determine whether the scleral reaction was a primary thermal effect. Histologic examination of treated specimens showed thickening of normal rabbit sclera with preservation of the underlying normal ocular structures. Electron microscopic examination of treated sclera showed newly formed collagen fibrils adjacent to sclerocytes. These fibroblasts were activated, as manifested by well-developed rough-surfaced endoplasmic reticulum and hypertrophic Golgi complexes.

Animals↗

Iodothiouracil as a melanoma localizing agent.

Thiouracil and various derivatives are selectively incorporated into the melanin pigment of melanomas during biosynthesis by serving as false melanin precursors. Using the transplantable Harding-Passey melanoma carried in BALB/c mice, we have extended our previous studies with sulfur-35 (35S) thiouracil. The persistence of high levels of [35S]thiouracil in tumor for periods of up to 2 wk has been demonstrated; during this time the drug content in normal tissues returned to near background levels. The variety of iodine isotopes available makes iodothiouracil a particularly promising melanoma-localizing agent. Tumor uptake and biodistribution of [35S]thiouracil and iodothiouracil (both iodine-127 (127I) and iodine-125 (125I) labeled) have been compared and were found to be essentially the same. The selectivity of [125I]thiouracil for melanoma has been qualitatively demonstrated by autoradiography of whole-body sections and quantitated by analysis of tumor and selected tissues. Iodothiouracil was also shown to localize in remote secondary metastases using a metastatic variant of the Harding-Passey melanoma currently being developed in our laboratory. These studies confirm the melanoma localizing capabilities of an iodinated thiouracil, and therefore the potential of using iodinated thiouracil derivatives for diagnosis and therapy of melanotic melanomas.

Animals↗

Thermoradiotherapy for intraocular tumors.

We have developed and used a thermoradiotherapy (TRT) plaque to treat choroidal melanoma (Greene strain) in rabbits. A dual-therapy scleral plaque delivers localized hyperthermia (4.8-gigahertz microwave) and ionizing radiation (iodine I 125). Transscleral treatment involves placement of a TRT plaque on bare sclera at the base of an intraocular tumor. Therapeutic doses of ionizing and hyperthermic radiation are then simultaneously delivered to the intraocular tumor. Sparing of normal ocular structures outside the treatment area after the combined therapy has been noted on clinical, gross, and histologic examinations. Our study suggests that the TRT plaque described satisfies the requirements for dual-modality treatment of choroidal melanoma.

Animals↗

0.6 T magnetic resonance imaging of the orbit.

Magnetic resonance (MR) imaging of the orbit was performed with a 0.6 T superconducting imaging system in 100 patients with normal orbits who were being evaluated for brain pathology and in 21 additional patients with a variety of orbital lesions to determine the efficacy of MR imaging in displaying orbital abnormalities. Usually, MR studies were performed using a multislice technique with multiple spin-echo pulse sequences and 30, 60, and 90 msec echo times and 500, 1500, and 2000 msec repetition times. Using section thicknesses of about 8 mm, imaging was performed in the transaxial, coronal, and sagittal projections. Pixel size was 0.9 X 1.8 mm, and the examination took about 30 min. The MR findings were compared with computed tomographic (CT) findings in all cases. Either combined axial and coronal studies of 5-mm-thick sections or a thin axial study of 1-mm-thick sections followed by reformatting techniques to obtain multiplanar images was used. Contrast enhancement was used in the CT studies. Both MR and CT clearly demonstrated the soft-tissue abnormality in all cases except two, in which MR failed to detect the abnormality. In one, MR failed to detect a small retrobulbar hemorrhage that occurred after a surgical procedure for retinal detachment. In the second case, rather extensive calcification in the posterior choroidal layers and lens was not detected by MR imaging. In several other cases, MR provided information beyond that obtained with CT. MR has the advantage of providing exquisite anatomic detail in multiplanar images, and it appears to be more sensitive than CT in detecting small, subacute and chronic hemorrhage within soft-tissue masses in the orbit and in detecting ischemia of the globe. CT is superior to MR imaging in portraying fine bone detail.

Adult↗

Hyperthermic treatment of intraocular tumors.

A 5.8-gigahertz (GHz) ophthalmic microwave applicator was used to treat choroidal melanoma (Green strain) in rabbits. High-frequency electromagnetic radiation provides a favorable dose distribution to induce local hyperthermia in the treatment of intraocular tumors. Heating of the neoplasm, while sparing normal ocular structures, is best accomplished by a transscleral approach. A hyperthermia plaque is placed on the sclera at the base of the intraocular tumor. Contact (resistive) heating and electromagnetic radiation (radiofrequency and microwave) are best suited to a plaque technique. The advantages of electromagnetic heat induction, as compared with contact heating, are twofold: the depth of hyperthermic penetration can be modulated by frequency selection, and the tissues with low water content (sclera) remain relatively unaffected by microwaves. The 5.8-GHz ophthalmic microwave applicator satisfies the requirements for local hyperthermic treatment of intraocular tumors.

Animals↗

Ocular anatomy for nuclear medicine.

The small size of the eye has precluded many efforts to image ophthalmologic disease processes. An understanding of those areas where nuclear medicine has been successful in ophthalmology requires a review of the appropriate anatomy. The accessibility of the nasolacrimal system and its pumping action have allowed for a unique physiologic appraisal with nuclear medicine techniques. The "magic bullet" that has eluded the search of oncology has left ophthalmologists without a practical diagnostic modality for ocular cancers. However, by placing detection devices in close proximity to these tumors, some useful information can be obtained. Unfortunately, this requires surgical dissection. New techniques have already been introduced into ophthalmology (fluorophotometry) in diabetic disease of the eye and nuclear medicine may have a considerable impact in this area. Understanding the anatomy of the retinal capillaries and larger vessels is essential to the reading of the pioneering work of Freeman and coworkers.

Eye↗

Tumor detection with radiopharmaceuticals.

The most common primary ocular tumor in adults is malignant melanoma of the choroid. Metastatic tumors to the choroid occur with the same frequency. The radioactive phosphorous uptake test is used most often as a nuclear diagnostic test. The test does not differentiate melanomas from metastases, and it is necessary to perform surgery for proper placement of a detection device within a distance of 1-2 mm of the tumor. These deficiencies leave ophthalmologists with a pressing need for a gamma-emitting radiopharmaceutical that would facilitate noninvasive identification of choroidal melanoma. This need is made more urgent by the fact that recently, radiation therapy has been used to treat these tumors rather than enucleation. Eyes then harbor irradiated melanoma whose status is unknown. The tumor rarely decreases in size more than 25% to 50%. There is thus a need for a specific diagnostic test to assess the nature of the tumor and the effectiveness of therapy.

Choroid Neoplasms↗

Radioactive phosphorus uptake test for the diagnosis of malignant melanoma of the choroid.

The most frequently used radioisotope in ophthalmology is radioactive phosphorus (32P). Since its introduction into ophthalmology in 1951, it has been used primarily as an aid in the diagnosis of malignant melanoma of the choroid. During the thirty years of clinical use, the indications for this test have been clearly defined. The maximum tissue penetration of 32P is 7 mm. Surgical dissection is therefore frequently necessary to enable the ophthalmologist to place the Geiger-Muller probe on the sclera in proximity to the tumor. False positive and false negative results are unusual and the test is between 96% and 100% accurate.

Choroid Neoplasms↗

Iodine-125 irradiation of choroidal melanoma. Clinical experience.

Twenty-nine patients with choroidal melanomas were treated with iodine-125 seeds in gold scleral plaques. Iodine-125 emits low energy 25 KeV photons which are attenuated by the side and back of the plaques so that the radiation is "directed" towards the choroidal tumor. The anticipated therapeutic benefits of using a low energy isotope and directional applicators have been realized. There has been a marked reduction in ocular complications in the nine medium and 20 large melanomas so treated. Our complication rate was 34% with a mean follow-up of 38 months. This is a lower complication rate, with longer follow-up, and in larger tumors than that reported with the use of cobalt-60, ruthenium-106 or ion beam. Three patients with large tumors and two patients with medium tumors died of metastasis. This compares favorably to results of similarly sized melanomas treated by enucleation.

Adult↗

Differential radioactivity monitor for noninvasive detection of ocular melanoma.

A novel instrument for the noninvasive diagnosis of ocular melanoma was evaluated with 67Ga in patients with pathologically confirmed tumours. The decision to enucleate was based on the results of standard ophthalmic diagnostic modalities including the 32P uptake test. The differences in the ocular radioactivity at 48-72 h predicted the presence of ocular abnormality. A positive differential result was found for tumours having a volume of greater than 600 mm3. Smaller tumours indicated lower retention of 67Ga in the eye with the tumour, whereas control subjects showed less than 2% differences in the radioactivity present in either eye.

Choroid Neoplasms↗