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Biomedical subjects

J Seddon

Publications and source records attributed to J Seddon.

17 recordsLinked to original sources

Effects of chronic alcohol treatment on the synthesis, sialylation, and disposition of nascent apolipoprotein E by peritoneal macrophages of rats.

BACKGROUND: Plasma apolipoprotein (apo) E, a sialoprotein, plays an important role in reverse cholesterol transport. Previously, we showed that chronic alcohol consumption impairs glycosylation of apo E in rat liver. Peritoneal macrophages are another significant apo E synthesis site. OBJECTIVE: The main purpose of this study was to determine the effects of chronic alcohol feeding of rats on the synthesis, sialylation, and sialic acid content of macrophage apo E and its ability to bind to the HDL(3) molecule in vitro. DESIGN: Rats were fed an alcoholic diet or an isoenergetic control diet for 8 wk, after which peritoneal macrophages isolated from them were cultured and analyzed for apo E metabolism. RESULTS: Macrophages from alcohol-fed rats accumulated 33.3% more (P < 0.05) cholesterol than did those from control rats when incubated with acetylated LDL. These macrophages showed a 51-57% lower relative sialylation rate of apo E (P < 0.001) but no significant difference in relative protein synthetic rate. The sialic acid content of the intracellular and secreted forms of apo E was reduced by 41.8% (P < 0.001) and 50.3% (P < 0.001), respectively, with chronic alcohol treatment. Secretion of newly synthesized apo E was impaired by 53.7% (P < 0.001) and 26. 1% (P < 0.001) in the absence and presence of HDL in the medium, respectively. Macrophages of alcohol-treated rats secreted apo E with 47.6-67.2% lower (P < 0.001) HDL(3) binding ability; binding ability was restored completely by resialylation of the desialylated apo E. CONCLUSION: In rats, an alcohol-mediated decrease in sialylation rate resulting in loss of sialic acid residues in apo E impairs the ability of apo E to bind to HDL and consequently in defective reverse cholesterol transport.

Animals↗

The social body and the biomechanical body: can they coexist in nurse education?

The curricula of tertiary nursing courses usually involve a number of complementary strands. These include biological sciences, social sciences, behavioural sciences, other support subjects and clinical units. These different strands each, to some extent, present the nursing student with a dilemma as they may present entirely different models of the body. Explorations of this dilemma show that students are also being presented with different models of illness and different conceptions of appropriate health care response to illness. The question is then raised as to which of these approaches most accurately reflects the realities of nursing practice.

Biomechanical Phenomena↗

Nurses, doctors and the body of the patient: medical dominance revisited.

Medical dominance is one of the most obvious features of the health care system and is particularly apparent in the relationship between doctors and nurses. Reasons given for the subordination of nurses to doctors have included matters of gender, class and state patronage of medicine. This paper, through an examination of university curricula and journal content, explores the notion that control over the model of the body is a major way in which medicine preserves its dominance over nursing. One reason for medicine maintaining its superior position is that nursing is not challenging this model of the body.

Biomechanical Phenomena↗

Mortality from second tumors among long-term survivors of retinoblastoma.

BACKGROUND: Children diagnosed with retinoblastoma, a rare cancer of the eye, tend to develop and die of second primary cancers in childhood and adolescence, but few investigations have followed patients into adulthood. Retinoblastoma is frequently caused by inherited mutations of the RB1 tumor suppressor gene. Most patients with germline (hereditary) mutations have bilateral disease. PURPOSE: We sought to quantify the mortality from second malignancies among long-term survivors of retinoblastoma and to identify factors that predispose to these deaths. METHODS: A retrospective cohort study examined mortality among 1603 patients enrolled at 1 year after diagnosis of retinoblastoma during the period 1914-1984. Data on demography, family history, and retinoblastoma treatment were collected by medical chart review and questionnaire interview. Number of deaths, by cause, was compared with the corresponding expected figure based on U.S. mortality data for the general population for 1925-1990. RESULTS: Follow-up was complete for 1458 patients (91%) for a median of 17 years after retinoblastoma diagnosis. A total of 305 deaths occurred, 167 of them from retinoblastoma. There were 96 deaths from second primary tumors (relative risk [RR] = 30), 21 from other known causes (RR = 1.0), and 21 from ill-defined or unknown causes. Statistically significant excess mortality was found for second primary cancers of bone, connective tissue, and malignant melanoma and benign and malignant neoplasms of brain and meninges. Among 919 children with bilateral retinoblastoma, 90 deaths from second primary tumors occurred (RR = 60). Deaths from second tumors were more frequent among females (RR = 39) than males (RR = 22) (P = .007). The cumulative probability of death from second primary neoplasms was 26% at 40 years after bilateral retinoblastoma diagnosis, and additional cancer deaths occurred thereafter. Radiotherapy for retinoblastoma further increased the risk of mortality from second neoplasms. An excess of mortality from a second cancer, not seen in prior studies, was found among the 684 children with unilateral disease (RR = 3.1; 95% confidence interval = 1.0-7.3). CONCLUSIONS: These findings implicate germinal mutations in the retinoblastoma gene in second cancer mortality. Radiotherapy treatment for retinoblastoma appears to further enhance the inborn susceptibility to development of a second cancer. IMPLICATIONS: Patients with retinoblastoma, particularly bilateral retinoblastoma, should have careful follow-up, and interventions should be developed to reduce mortality from a second cancer.

Adolescent↗

Standardized data collection and coding in eye disease epidemiology: the Uveal Melanoma Data System.

The Uveal Melanoma Data System of the Massachusetts Eye and Ear Infirmary is a computerized data-base designed for data management and analysis with a broad range of clinical research applications. The system was created in 1980 and has evolved to include standardized data collection forms for all aspects of uveal melanoma patient care such as initial examination, treatment, and follow-up, as well as precoded forms for computer entry, which facilitate quality control measures and data analysis. Excerpts from current versions of these forms are presented. The Uveal Melanoma Data System has been used for a variety of clinical epidemiologic investigations. Examples of its application, including descriptive studies, prognostic factor studies, and treatment evaluations, are discussed. The model has potential broad application for clinical ophthalmic research in other specialty areas.

Data Collection↗

Increased scleral rigidity and age-related macular degeneration.

The coefficient of scleral rigidity of the eyes of 29 patients with age-related macular degeneration (ARMD) was significantly higher than the rigidity of 25 control patients, frequency matched for age. The data suggest that an increased scleral rigidity may be a significant risk factor for the development of the disorder.

Aged↗

Cobalt plaque versus enucleation for uveal melanoma: comparison of survival rates.

Two hundred and twenty-three patients treated by cobalt plaque for uveal melanoma were compared with 416 patients treated by enucleation for uveal melanoma in terms of patient survival. The median follow-up time for the patients treated by cobalt plaque was 4.3 years. Kaplan-Meier survival curves were calculated up to five years following treatment based on time to tumour-related deaths. Cox's proportional hazards multivariate analysis was performed to determine which variables were related to melanoma-related deaths while controlling for age, size, and location of the tumours. Statistically significant predictive factors were location of tumour and largest tumour dimension. There was not a statistically significant difference in survival between patients treated by cobalt plaque and those treated by enucleation.

Adolescent↗

Hepatoblastoma in families with polyposis coli.

We observed hepatoblastoma in four unrelated children who have a family history of polyposis coli and found this association in ten other kindreds in the literature. The one child in our series who has survived hepatoblastoma showed multiple colonic adenomas at 7 years of age. She and eight affected maternal relatives also had congenital hypertrophy of the retinal pigment epithelium, a new marker of gene carriers in some polyposis coli families. These findings suggest that childhood hepatoblastoma is an associated feature of familial polyposis coli.

Adenomatous Polyposis Coli↗

A method for assessing potential bias among cancer patients recorded as "dead of other causes." Application to cases of intraocular melanoma.

By applying the Cox regression model to 226 cases of intraocular melanoma, the authors detected a statistical association between tumor-related measurements and 42 deaths that were recorded as due to causes other than melanoma within 10 years of follow-up. This association may reflect a number of events, including errors in assignment of cause of death and confounding from any one of several sources.

Eye Neoplasms↗

Current results of proton beam irradiation of uveal melanomas.

Proton beam irradiation has been used for the treatment of 241 uveal melanomas over the past 7 1/2 years. Twelve melanomas (5%) were small, 99 (41%) medium, 103 (43%) large and 27 (1%) extra-large melanomas. The mean length of follow-up was 21 months and the median 15 months. Ninety-four percent of the treated lesions with a follow-up more than two years and 65% of tumors with shorter follow-up showed regression. The most recent visual acuity was 20/40 or better in 47% and 20/100 or better in 66%. Ten eyes were enucleated because of complications (9) or continued tumor growth (1). Thirteen patients developed metastases from 4 to 50 months of treatment. Our data indicate that proton irradiation can be used to treat melanomas of various sizes and in a variety of locations, and preliminary results suggest that proton therapy has no deleterious effect on the likelihood of the development of metastases.

Adolescent↗

Progress in low-LET heavy particle therapy: intracranial and paracranial tumors and uveal melanomas.

The Harvard Cyclotron Laboratory in collaboration with the Department of Radiation Medicine of the Massachusetts General Hospital and the Retina Service of the Massachusetts Eye and Ear Infirmary provides low-LET heavy particle therapy with 160 MeV protons. The improved dose distribution of protons results from their physical characteristics. A total of 965 patients have been treated as of December 31, 1984. Dose is expressed in units of cobalt gray equivalent (CGE) which is the dose in Gy multiplied by the RBE (1.1) for modulated protons relative to 60Co radiation. Sixty-seven patients with chordomas or low-grade chondrosarcomas of the base of skull or cervical spine have received proton treatment. Forty-three of these patients have been followed for at least 8 months with a median follow-up of 27 months. The median dose is 69 CGE. The 3-year actuarial local control rate is 89%. Seven patients with gliomas, eight with craniopharyngiomas, and six with meningiomas have also received proton radiation treatments. A total of 615 patients with uveal melanomas have received a median dose of 70 CGE in five fractions. Tumor regression has been seen in 94% with 66% having vision of 20/100 or better.

Actuarial Analysis↗

Preliminary results of proton beam irradiation of macular and paramacular melanomas.

Proton beam irradiation has been used for the treatment of 60 eyes with choroidal melanomas located 3 mm or less from the fovea. The average follow-up period was 18 months. 86% of the treated lesions showed regression at the time of this analysis, and the 14% that did not were followed up for less than a year. Visual acuity remained the same in 47% of the treated eyes, improved in 20%, and deteriorated in 33%. 58% of the treated eyes had visual acuity of 20/100 or better at the last follow-up examination. Radiation vasculopathy with macular oedema was the most common complication, and it was observed in 22% of the treated eyes. These preliminary observations suggest that proton beam irradiation may be a reasonable alternative to enucleation even for this group of choroidal melanomas, which is considered unfavourable in respect of the preservation of visual function.

Adolescent↗

MR imaging of enucleated human eyes at 1.4 tesla.

Proton magnetic resonance images obtained for nine human eyes with various pathology were correlated with histological findings. One eye with retinal gliosis, three eyes with malignant melanoma, one eye with extraocular squamous cell carcinoma, one pair of eyes with incipient senile cataracts, and one pair of eyes with diabetic cataracts were examined at a field strength of 1.4 T using spin-echo and inversion-recovery signal acquisition protocols. Eyes were examined unfixed and within 24 h of enucleation. Most images were characterized by a homogeneous vitreous and a lens made conspicuous by its low-signal intensity. The anterior chamber, ciliary body, and optic nerve could be seen, but the retina and choroidal layers could not be distinguished. The dynamic range of vitreal signal was quite wide and allowed all lesions in this series to be well-contrasted against the vitreous. In addition, lenticular edema accompanying cataract formation gave a strong signal. Signal differences were apparent between paired cataractous lenses with a 1.6% difference in water content. Magnetic resonance imaging is a modality that promises good contrast for ocular imaging and sensitive detection of incipient cataractous change.

Adult↗