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Biomedical subjects

S Packer

Publications and source records attributed to S Packer.

At least 37 records · Page 2Linked 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

Treatment of minimal brain dysfunction in a young adult.

A discussion of the clinical picture and treatment of minimal brain dysfunction in post adolescence is presented. Small amounts of methylphenidate appear to have a salutary effect on symptoms such as irritability, moodiness, restlessness and poor concentration .

Adolescent

The effect of zinc on insulin metabolism.

Experiments were designed to study the effect of Zn on in vivo and in vitro insulin metabolism. The in vivo experiments involved pretreating mice with either Zn or Na, followed by ip [125I]iodoinsulin injection. Pretreatment of mice with Zn resulted in an accelerated and increased magnitude of binding of [125I]iodoinsulin to the liver compared to mice pretreated with Na. Results are submitted which support the probability that the changes in the amounts of intact and degraded insulin in circulation with time are related to the binding and degradation of insulin in the liver rather than in the kidney. In vivo ip injected insulin was demonstrated to preferentially bind to the plasma membrane of the liver. Liver plasma membranes isolated from mice pretreated with Zn bound more [125I]iodoinsulin than plasma membranes of Na-pretreated mice. In vitro experiments employing isolated liver plasma membranes demonstrated that added Zn increased the binding and inhibited the degradation of insulin. Evidence is presented that supports the concept that two receptors exist, one at which degradation of [125I]iodoinsulin occurs and another at which degradation does not occur.

Animals

The ultrasound guided 32P test.

The accurate and early diagnosis of intraocular malignant melanoma in eyes with opaque media remains a diagnostic problem. Ultrasonography and the radioactive phosphorus (32P) uptake test have been used separately as modalities for diagnosis of choroidal melanoma. However, their combined use has received limited attention. This report presents our experience in 5 cases with the combined use of a contact B-scan ultrasound unit and a posterior eye probe. In all cases we were able to accurately perform the 32P uptake test with simultaneously ultrasound visualization of the tumor and the probe.

Aged

Metal isotopes used as radioactive indicators of ocular melanoma.

We studied radioactive metal compounds to determine their localization in malignant Greene melanoma in the eye of the Syrian golden hamsters. Scintigraphy of an ocular melanoma was achieved with several radioactive metals: radioactive indium(111In)-bleomycin, radioactive gallium (67Ga)-citrate, and radioactive lead (203Pb)-tris. The 111In-bleomycin had the highest tumor uptake (5.45% dose/g), but not the highest tumor-to-background ratios. The 67Ga-citrate had a maximum tumor uptake of 4.87% dose/g at 48 hours. The 111In-chloride had a melanoma uptake of 2.26% dose/g, while with 203Pbtris the uptake was 1.61% dose/g. These uptake ratios compare favorably with that of radioactive phosphorus (32P)-2.21% dose/g. Noninvasive localization of malignant melanoma in the eye was accomplished with metal isotopes. Detailed analysis of in vitro uptake date by tumor and background tissues revealed the optimum time for scanning and precluded unnecessary trials.

Animals

Radiation therapy of choroidal melanoma.

During the past 8 years, 32 patients with melanoma of the choroid have been treated with cobalt-60 ophthalmic applicators. Excluding three patients lost to follow-up, 24 patients who have now been observed for at least 3 years after treatment form the subject of this study. Each application but two delivered 8,500 to 10,000 rads to the tumour apex. A second application was performed in large tumours showing a poor response to the initial plaque treatment. The factors affecting results include age of the patient, tumour size, total dose delivered, and dose rate. Three out of seventeen patients with tumour diameters greater than 12 mm died of their disease with pulmonary and/or liver metastasis. Three eyes required enucleation and no residual tumour was found in two specimens. Three patients, average age 76 years, died from causes other than melanoma. An 83 per cent relative survival, excluding the three patients lost to follow-up, compares favourably with enucleation. The low incidence of metastasis after radiotherapy suggests augmentation and/or continuation of the host's immune response. Low energy radiation using Iodine-125, with its unusual protective characteristics is ideal for treatment of choroidal melanoma.

Aged

Urinary outputs of oxalate, calcium, and magnesium in children with intestinal disorders. Potential cause of renal calculi.

24-hour urinary outputs of oxalate, calcium, and magnesium have been determined in a total of 62 children aged 3 months to 17 years who fell into the following groups: (i) 16 normal controls, (ii) 3 with primary hyperoxaluria, (iii) 9 with small and/or large intestinal resections, (iv) 9 with untreated coeliac disease, (v) 5 with pancreatic dysfunction, and (vi) a miscellaneous group of 20 children with a variety of intestinal disorders. Taken as a whole, 58% of patients with intestinal disorders had hyperoxaluria, and of these 7% had urinary outputs of oxalate which fell within the range seen in primary hyperoxaluria. The proportion of children with hyperoxaluria in the different diagnostic groups was as follows: intestinal resections (78%), coeliac disease (67%), pancreatic dysfunction (80%), and miscellaneous (45%). 35% of the patients with hyperoxaluria had hypercalciuria, whereas magnesium excretion was normal in all subjects studied. In 2 patients treatment of the underlying condition was accompanied by a return of oxalate excretion to normal. These results indicate that hyperoxaluria and hypercalciuria are common in children with a variety of intestinal disorders, and that such children may be at risk of developing renal calculi without early diagnosis and treatment.

Adolescent

Cellular infiltrate of the jejunum after re-introduction of dietary gluten in children with treated coeliac disease.

Jejunal lamina propria plasma cells and eosinophils and intraepithelial lymphocytes were raised in coeliac children on gluten-containing diets, but only intraepithelial lymphocytes were increased in patients on gluten-free diets. In contrast, lamina propria lymphocytes were reduced in children with coeliad disease on gluten-containing diets but were normal in paitents on gluten-free diets. In children with coeliac disease who were studied serially, lamina propria plasma cells and eosinophils and intraepithelial lymphocytes increased, and lamina propria lymphocytes decreased, within three months of the reintroduction of gluten to the diet. These observations are essentially similar to those made in the adult form of the disease and suggest that more than one type of immunological reaction is involved in the pathogenesis of the jejunal lesion.

Adolescent