Anorexia nervosa--more than an eating disorder.
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Anorexia Nervosa↗
Biomedical subjects
J D Russell
Publications and source records attributed to J D Russell.
Update in eating disorders.
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Anorexia Nervosa↗
Biological and biochemical anti-human immunodeficiency virus activity of UC 38, a new non-nucleoside reverse transcriptase inhibitor.
UC 38, a simple analog of oxathiin carboxanilide, UC 84, lacking the oxathiin ring, was found to be a potent inhibitor of human immunodeficiency virus (HIV)-1-induced cell killing and HIV replication in a variety of human cell lines, as well as in human peripheral blood lymphocytes and macrophages. UC 38 was active against a wide range of biologically diverse laboratory and clinical strains of HIV-1. However, UC 38 was inactive against HIV-2 and both nevirapine- and pyridinone-resistant strains of HIV-1. UC 38 selectively inhibited HIV-1 reverse transcriptase (RT), but not HIV-2 RT. Combination of UC 38 with 3'-azido-3'-deoxythymidine synergistically inhibited HIV-induced cell killing. An HIV-1 isolate resistant to UC 38 was selected in cell culture, and the mutations in the RT nucleotide sequences were determined. Comparison with the wild-type RT sequence revealed an amino acid change at position 181 (Tyr to Cys). The UC 38-resistant virus was found to be cross-resistant to a variety of structurally diverse non-nucleoside RT inhibitors. UC 38 was susceptible to rapid degradation in vitro and in vivo; yet, nontoxic in vivo concentrations of UC 38 many-fold in excess of the in vitro effective concentrations could be achieved and maintained after s.c. or p.o. administration in hamsters. These results establish UC 38 as a new chemotype within the general class of HIV-1-specific RT inhibitors. The favorable physical characteristics, lack of toxicity, potency and bioavailability of UC 38 may make it a candidate for combination chemotherapy of acquired immune deficiency syndrome.
Animals↗
Cordectomy: a solution to Teflon granuloma of the vocal fold.
Teflon injection has been widely used for the treatment of unilateral vocal fold paralysis. Complications are few and infrequent. Overinjection and Teflon granuloma are the two commonest problems encountered. Treating such complications and restoring vocal quality is widely regarded as difficult. Endoscopic transmucosal excision of the excess Teflon and/or granuloma has not been successful in improving phonatory quality. Cordectomy is proposed as an alternative surgical approach for managing both the convex vocal fold and Teflon granuloma after injection.
Female↗
Glucocorticoid regulation of elastin synthesis in human fibroblasts: down-regulation in fibroblasts from normal dermis but not from keloids.
Keloids arise as benign connective tissue masses at sites of injury in genetically predisposed individuals. In addition to excessive collagen accumulation, there is biochemical and histologic evidence of elastic tissue. Previous studies showed that glucocorticoid regulation of collagen synthesis differs in fibroblasts from normal adult dermis and keloids. To define further the abnormal regulation of matrix synthesis in keloid fibroblasts, we examined glucocorticoid regulation of elastin synthesis. The basal level of elastin synthesis was significantly higher in keloid than in normal cells, and hydrocortisone reduced synthesis of elastin and elastin mRNA in normal but not in keloid fibroblasts. We had shown previously that fibroblasts from fetal dermis resembled keloid fibroblasts in glucocorticoid regulation of growth and collagen synthesis. In this study, glucocorticoids failed to down-regulate elastin synthesis in fetal cells that had not differentiated to produce normal levels of elastin, whereas fetal cells with normal elastin production exhibited glucocorticoid down-regulation. Abnormal regulation in keloid cells was independent of cell density and was confined to fibroblasts cultured from the keloid nodule. These findings reinforce the conclusion that a matrix-regulatory pathway is deranged in these focal lesions. Coordinate down-regulation of collagen and elastin by hydrocortisone in normal adult dermal fibroblasts and the failure of hydrocortisone to down-regulate synthesis of either protein in keloid cells support the existence of common elements in the regulatory pathways of these two matrix proteins.
Adult↗
Structure-activity and cross-resistance evaluations of a series of human immunodeficiency virus type-1-specific compounds related to oxathiin carboxanilide.
A series of compounds related to the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) oxathiin carboxanilide (UC84) were evaluated for activity against the human immunodeficiency virus (HIV) to determine structural requirements for anti-HIV activity. Twenty-seven compounds representative of the more than 400 Uniroyal Chemical Company (UC) compounds were evaluated for structure-activity relationships. Several of the compounds evaluated were highly active, with 50% effective concentrations in the nanomolar range and therapeutic indices of > 1,000. Highly synergistic anti-HIV activity was observed for each compound when used in combination with 3'-azido-3'-deoxythymidine; additive to slightly synergistic interactions were observed with the compounds used in combination with dideoxycytidine. In combination with the NNRTI costatolide, only UC38 synergistically inhibited HIV type 1. Residues in the RT which, when mutated, impart resistance to the virus isolates selected in cell culture, against virus variants with site-directed mutations, and against RTs containing defined single amino acid changes. The mutations included changes in RT amino acids 100, 101, 103, 106, 108, and 181. The results with isolates selected in cell culture indicate that the carboxanilide compounds interact with the RT at two vulnerable sites, selecting UC-resistant virus isolates with the Y-to-C mutation at position 181 (Y181C) or the L100I substitution. A resistant virus isolate containing both Y181C combination with calanolide A, an NNRTI which retains activity against virus with the single Y181C mutation, UC10 rapidly selected a virus isolate with the K103N mutation. The merits of selecting potential candidate anti-HIV agents to be used in rational combination drugs design as part of an armamentarium of highly active anti-HIV compounds are discussed.
Antiviral Agents↗
Excessive physical activity in dieting disorder patients: proposals for a supervised exercise program.
A relationship between starvation and hyperactivity has been observed in animal models, in experiments with human subjects, and in dieting disorder patients. Since the earliest descriptions of anorexia nervosa, excessive physical activity has figured prominently as a symptom of the illness, yet little attention has been directed towards this phenomenon. The aims of this paper are to review the published literature, to report our experience of the role of physical overactivity in the clinical presentation of dieting disorders, to discuss its implications for treatment, and to propose a supervised exercise program by which overactivity may be addressed specifically in the treatment of these patients.
Adolescent↗
Protein repletion and treatment in anorexia nervosa.
Body fat and total body nitrogen (TBN) were quantified before and after refeeding in 32 female anorexia nervosa patients and in 29 matched control subjects by using the techniques of anthropometry and in vivo neutron-capture analysis (IVNCA). Mean body weight of patients (mean body mass index; BMI, in kg/m2), 15.4 +/- 1.3, was 72.7% of that of control subjects, increasing to 89.8% of mean weight of control subjects after refeeding (mean BMI 19.0 +/- 1.2). Mean BMI of control subjects was 21.6 +/- 2.7. Compared with the control group, patients' nitrogen was initially depleted by 24.5%, increased by 18.4%, but remained 10.6% below control values (P < 0.001). Body fat was depleted by 58.4%, increased by 89.7%, but remained 21.8% below control values (P < 0.001). Thus, despite a greater initial depletion and subsequently a greater net gain, body fat remained relatively more depleted after treatment than did nitrogen and protein. Anorexia nervosa patients were shown to readily replenish protein during nutritional rehabilitation.
Adolescent↗
Treatment of anorexia nervosa.
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Aftercare↗
Effect of refeeding and exercise in restoration of body protein in anorexia nervosa.
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Adipose Tissue↗
Brachytherapy for recurrent nasopharyngeal and naso-ethmoidal tumours.
Recurrent or persistent carcinoma of the nasopharynx or naso-ethmoid region occurs even after combined surgery and radical external irradiation. The confined bony access and proximity of vital structures may compromise resection margins. Brachytherapy using implantable radioactive gold or iodine seeds is a useful adjunct to the skull base surgeon in eliminating residual microscopic disease. We report nine cases with recurrent or persistent disease of the nasopharynx or naso-ethmoid regions treated with brachytherapy with encouraging results.
Adolescent↗
What causes acute otitis externa?
External otitis is an extremely common condition and can affect between five to twenty per cent of the patients attending ENT clinics (Hawke et al., 1984). Its precise pathogenesis remains unclear, despite several aetiological classifications in the literature. The aim of this study was to investigate the relationship between infection, water exposure and trauma and the development of acute otitis externa. The study comprised 100 patients with their first attack of otitis externa and 150 age and sex matched controls. In only 40 per cent of cases could a primary microbiological cause be found. There was no significant statistical difference found between the two groups regarding the use of agents capable of traumatizing the external canal. Regular swimming, showering and hair washing were significantly more common in patients with acute otitis externa. Allergic disorders were nearly three times more common in the external otitis group suggesting a possible immunological aetiology.
Acute Disease↗
Innervation of the rat tympanic membrane from the superior cervical and glossopharyngeal ganglia.
True Blue and Fluorogold were applied to the external surface of the tympanic membrane and middle ear mucosa of Sprague-Dawley rats and neurons in the superior cervical and glossopharyngeal ganglia were labelled with these retrograde tracer dyes. Dye absorption was poor from the tympanic membrane unless the keratinized layer was damaged with crystalline silver nitrate prior to dye application. Stained neurons were scattered throughout the superior cervical ganglion with no evidence of somatotopy. Several neurons in the glossopharyngeal ganglion stained with both dyes when these had been simultaneously applied to both sites in single animals. There was no evidence of dual staining of neurons in the superior cervical ganglion.
Animals↗
Keloid fibroblasts are refractory to inhibition of DNA synthesis by phorbol esters. Altered response is accompanied by reduced sensitivity to prostaglandin E2 and altered down-regulation of phorbol ester binding sites.
To investigate abnormal growth regulation in keloid fibroblasts, responses to phorbol esters were examined. Treatment of quiescent cultures with phorbol 12-myristate 13-acetate (PMA) blocked a normally occurring (20-24 h) peak of serum-stimulated thymidine incorporation in normal and keloid cells. In keloid fibroblasts PMA induced a delayed peak of DNA synthesis. When indomethacin was added with PMA the delayed peak appeared in normal fibroblasts. The ED50 for inhibition of the 20-24-h peak was 1 nM, whereas the delayed peak required a 50-fold-higher PMA concentration. In both cell types PMA induced prostaglandin E2 (PGE2) synthesis, and exogenous PGE2 caused 50% inhibition of the 20-24-h peak. When PMA and indomethacin were added with PGE2 the delayed peak was inhibited 90% in normal fibroblasts, whereas inhibition of keloid cells was the same as with PGE2 alone. Normal and keloid fibroblasts had the same number of phorbol ester binding sites. However, in normal cells, phorbol 12,13-dibutyrate bound with greater affinity, and down-regulation of phorbol ester binding occurred to a greater extent. These findings suggest that altered expression of protein kinase C isozymes or another molecule that binds phorbol esters may play a role in abnormal growth regulation of keloid cells.
Binding Sites↗
Electron beam versus photon beam radiation therapy for the treatment of orbital lymphoid tumors.
Shielding the lens of the eye while treating orbital lymphoid tumors and achieving a relatively homogeneous dose can be a dosimetric challenge. There are many clinical cases of tumors close to one or both eyes, where it is desirable to spare the lens as much as possible. We will show isodose curves comparing direct anterior fields using various electron beam energies to a single 6 mv photon beam to a multifield combination. The presence of an eye shield in a photon beam may impair the dose distribution at the back of the eye to an undesirable degree. The strong in-depth dose drop-off in electrons and the ease with which the beam can be intercepted suggests that an electron beam with an eye shield may offer advantages. We designed a suspended movable lens shield .8 cm wide with a height of 4.5 cm made of cerrobend surrounded by a brass cylinder mounted to a thin plexiglass plate to insert into a Varian electron 6 x 6 cone. A 1.5 cm gap between block and eye surface was used. Verification of dose distribution under the lens shield was obtained by film dosimetry.
Humans↗
Necrotizing sialometaplasia.
Necrotizing sialometaplasia is a benign self-limiting disorder which can simulate malignancy. We report the third such case of nasal fossa involvement in the literature. The pathology of this condition is discussed.
Humans↗
The quality of life in renal transplantation--a prospective study.
Methodologically sound measures of quality of life are required to judge accurately the impact of successful renal transplantation on patient well-being. The time trade-off (TTO) method is a reproducible and valid measure which we used to prospectively assess changes in the quality of life of 27 patients on maintenance dialysis who subsequently underwent renal transplantation. TTO scores approaching 0 signify a very poor quality of life, while scores approaching 1 represent perfect health. Of 98 dialysis patients who completed baseline TTO interviews, 31 consecutive patients subsequently received 28 cadaveric and 3 living related kidney transplants. Four of 31 patients did not complete a second TTO assessment, because of death in 2 patients and graft loss in 2 others. The remaining 27 patients completed a second TTO interview an average of 30.9 months following transplantation (range 1.5-52, 95% confidence interval [CI] 24.4-37.5) and formed the study cohort. At the time of study the mean serum creatinine for the cohort was 173 mumol/L (range 90-290, 95% CI 152-195 mumol/L). The employment rate rose 27% following transplantation (P = 0.10); but when males alone were analyzed, a significant increase of 38% (P = 0.048) was noted. During the dialysis period, the mean baseline TTO score was 0.41 (95% CI 0.33-0.49), confirming the observations of others. Following transplantation, the mean TTO score rose to 0.74 (95% CI 0.67-0.81), a difference that is statistically significant (P < 0.001). The mean increase in TTO score observed as a result of successful transplantation was 0.33 (95% CI 0.26-0.40). This magnitude of improvement was found in 20 of 27 patients (74%), whose TTO scores lay within or above the 95% CI (0.26-0.40) for the mean change in score of 0.33. One patient's score fell, while the remaining 6 patients had improvements in their TTO score which fell below the lower 95% CI value (0.26) for the mean change in score. We conclude that the 95% CI of 0.26-0.40 identifies a range in which clinically important improvements in quality of life will be found for the majority of patients receiving successful kidney transplants.
Adult↗
The Parental Bonding Instrument in adolescent patients with anorexia nervosa.
The Parental Bonding Instrument (PBI) was administered to 54 adolescent patients with anorexia nervosa. Scores were compared with those of matched groups of normal and of nonanorectic adolescents referred for assessment to an adolescent psychiatric unit. Significant differences between the 3 groups were demonstrated with respect to care and protection dimensions. Overall scores of subjects in the anorectic group resembled those of normals rather than those of referred patients. Anorexia nervosa patients described their fathers and mothers as being more caring and their mothers as being less overprotective than did psychiatrically referred peers. The study raised questions concerning the use of the PBI in adolescents, in particular those with anorexia nervosa, and the role of the family in the aetiogenesis of this condition.
Adolescent↗