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Biomedical subjects

J How

Publications and source records attributed to J How.

At least 19 recordsLinked to original sources

Cognitive psychological studies of representation and use of clinical practice guidelines.

Clinical practice guidelines provide a means to enhance physician performance. This investigation was undertaken in an attempt to understand the nature of impact of guideline use on physician performance. We investigated the impact of (a) algorithmic-based and (b) text-based practice guidelines on clinical decision-making by physicians at varying levels of expertise. Data were collected using clinical scenarios and a think-aloud paradigm, both with (primed) and without (spontaneous) the use of the guidelines. The two guidelines used in the study were management of diabetes and screening for thyroid disease. The results show that guidelines were used as reminders for both experts and non-experts. Guidelines acted as an educational tool for non-experts by assisting in knowledge reorganization, particularly for the non-experts. Text and algorithmic guideline formats were both useful to physician performance depending on the purpose of use: solving clinical problems or learning. These results provide insights into how guidelines can be fine-tuned for different users and for different purposes. Empirical research, coupled with design principles from the cognitive sciences, can form an essential component of guideline design and development.

Adult↗

Effects of sleep deprivation on naval seamen: II. Short recovery sleep on performance.

Twenty male naval volunteers, aged 18 to 20 years, with 12 to 14 years of education, underwent a total sleep deprivation experiment on board a Republic of Singapore Navy landing ship in the South China Sea for a period of 42-102 hours. The sleep group comprised eight volunteers who dropped out at the 44th-46th h of the experiment and were randomly assigned to a 2 or 4 h sleep regime. The rest served as sleep-deprived controls. Neurobehavioural performance tests, profile of mood state and the Stanford Sleepiness Scale were applied 6 hourly starting from 6.00 am on the first experimental day. No thresholds were observed in the performance of tests related to manual tasks and subjective feeling, including naval tasks, mood and sleepiness scale during the sleep deprivation experiment. However, thresholds were observed in the performance of tests requiring cognitive and perceptive skills, including the grooved peg board, trail making, sea-shore rhythm, addition, digit span, digit symbol, flicker fusion and dynamometer tests. Performances in these tests were observed to deteriorate only after approximately 30 h of sleep deprivation. The Z score for the non-threshold tests (Z-N) deteriorated from -0.01 at the start of the experiment to 1.25 at the 42nd h of the experiment just before the imposed sleep and improved to 0.81 at the 48th h of the experiment just after the imposed sleep; and the Z score for the threshold tests (Z-T) varied from -0.07 at the start to 0.49 just before sleep (at the 42nd h) and to continuously deteriorate to 0.83 just after sleep (at the 48th h).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

A review of cases of pulmonary barotrauma from diving.

Pulmonary barotrauma is a condition where lung injury arises from excessive pressure changes. Five cases of pulmonary barotrauma from diving have been seen at the Naval Medicine and Research Centre from 1970 to 1991. Four suffered surgical emphysema while one developed cerebral arterial gas embolism (CAGE). These cases are presented and discussed, including the predisposing factors, common signs and symptoms and essential treatment of this condition.

Adult↗

Retinal artery occlusion in a diver.

The clinical manifestation of decompression disorders is highly variable, ranging from mild rashes or joint pains to central nervous system symptoms like scotomata, paralysis and death. The diagnosis is easily overlooked, especially if an occupational history is not obtained. Recompression treatment with hyperbaric oxygen is the specific treatment for decompression sickness and air embolism. Prompt recognition and treatment are vital to recovery. However, there is a place for treatment of decompression disorders and embolism even when significant delay of up to 14 days has occurred. This case report discusses decompression disorders in relation to an unskilled fisherman diver who present with retinal artery occlusion. Decompression disorder leading to retinal artery occlusion is a very rare presentation. The difficulty of diagnosis is discussed as well as the result of delayed hyperbaric treatment.

Adult↗

The application of disposable contact lenses in the Navy.

With the recent advent of disposable contact lenses, many of the problems which have been hindering the military application of contact lenses have been overcome. Fifty-five myopic naval personnel with no previous contact lens experience were put through a three-week study using these contact lenses. The aim was to test the feasibility of supplying bespectacled myopic seamen with contact lenses at the outset of operational missions. Seven developed conjunctival injection which caused them to discontinue contact lens wear. Of the remaining 48, however, a vast majority showed preference for contact lenses when compared to spectacles in the work environments that they were exposed to. With contact lenses, 95.8% had comparable or better vision during the day and 85.4% during the night. No serious ocular complications were noted and only minor findings were detected in the 96 eyes at the end of three weeks of contact lens wear.

Contact Lenses↗

Decompression sickness in the Singapore Mass Rapid Transit Project.

In the Singapore Mass Rapid Transit Project (MRT), 11 km of underground tunnels were built using compressed air. 1,737 compressed air workers (CAWs) were employed in the project. They underwent 188,538 man decompressions at the various compressed air worksites. 160 CAWs developed Type I decompression sickness (DCS) and 4 developed Type II DCS. This gave an overall incidence of 0.087%. The adoption of strict medical selection, strict adherence to decompression procedures and the provision for acclimatization of newstarters contributed greatly to this low incidence. Prompt treatment of DCS accounted for the low relapse rate. The clinical presentation of DCS is discussed here. Prevention of DCS by worksite environmental and work-practice monitoring are advocated.

Decompression Sickness↗

Acute decompression sickness in compressed air workers exposed to pressures below 1 bar in the Singapore Mass Rapid Transit project.

The Singapore Mass Rapid Transit (MRT) project started compressed air work in Oct 1984. Eleven km of underground tunnels out of 20 km were built using this method. Cases of decompression sickness (DCS) arising from compressed air work are rare with working pressures less than 1 bar gauge. However, there were 10 cases of DCS in the MRT project who were exposed to less than 1 bar pressure. The authors present their clinical features and attempt to explain the observations in relation to theories of bubble nuclei formation, gas loading and rate of decompression. The formation of bubble micronuclei are correlated with physical factors like heavy exertion, and the use of vibrating tools. The concept of extremely long tissue half-times in the absorption of nitrogen in the body is discussed as a contributory factor to the development of DCS under 1 bar.

Acute Disease↗

Effects of widespread dermatitis and topical steroid therapy on thyroid function tests.

Five patients with extensive dermatitis and 5 normal subjects were treated with topical betamethasone valerate 0.1% (Betnovate, Glaxo) 19-34 g daily for 4 days. Thyroid functions tests were not affected by the treatment but some patients with widespread inflamed skin demonstrated altered serum thyroid hormone levels as a result of the euthyroid sick syndrome.

Administration, Cutaneous↗

Role of autoantibodies in the pathogenesis and association of endocrine autoimmune disorders.

This review has focused on the nature and significance of aAB detected in the serum of patients with EAD. Although many antibodies are characteristically detected in the serum of patients with such disorders, only a few are of known pathogenic significance. Antibodies that react with soluble cytoplasmic antigens are not expected to be harmful. On the other hand, membrane or cell surface-directed antibodies are likely to be damaging, either by lysis of the cell membrane, or by reaction with hormone or other surface receptors. Clinically, measurement of aAB has important diagnostic and management value. Moreover, detection of certain antibodies before the onset of disease raises hope that the corresponding disorders may be preventable, e.g. by specific immunosuppression of those subjects, or patients, with positive tests. The possible role of aAB in the association of organ-specific AID by cross-reacting with shared epitopes in various tissues has been highlighted by the recent finding, from the authors' laboratory, of antibodies reactive with a 64-kDa membrane protein found in several tissues, including thyroid, eye muscle, and pancreas, which are frequent sites for autoimmune inflammation. Study of such antibodies and the molecular characterization of the corresponding antigens in the various involved tissues should provide information concerning the role of cross-reactivity in autoimmunity as well as leading to the development of specific immunotherapeutic agents.

Adrenal Cortex↗

A thyroid cytotoxic antibody that cross-reacts with an eye muscle cell surface antigen may be the cause of thyroid-associated ophthalmopathy.

A hitherto unrecognized thyroid antibody, which reacts with a thyroid cell surface antigen expressed on passaged thyroid cells, was identified in serum from patients with thyroid-associated ophthalmopathy using antibody-dependent cell-mediated cytotoxicity (ADCC) tests. The antibody was detected in 14 of 23 patients with Graves' hyperthyroidism (Gh) and associated ophthalmopathy, in 3 of 4 patients with Hashimoto's thyroiditis (HT) and ophthalmopathy, but in only 1 of 16 patients with Gh without clinically evident eye disease and 4 of 37 patients with HT without eye disease. The ADCC test also was positive in 2 of 30 patients with thyroid cancer, both of whom had had Gh and ophthalmopathy in the past. There was no correlation, in patients with ophthalmopathy, between the levels of the antibody (expressed as percent specific lysis) and the titers of antithyroid microsomal antibody measured using a hemagglutination assay. Based on the results of blocking experiments using mouse monoclonal antibodies against human thyroid peroxidase, now known to be the thyroid microsomal antigen, the corresponding antigen was not thyroid peroxidase. Moreover, the new antigen was expressed on cultured and passaged thyroid cells which do not express the microsomal antigen. In patients with ophthalmopathy there was a close correlation between the degree of lysis of passaged thyroid cells and that of eye muscle cells, and ADCC activity against passaged thyroid cells was absorbed by preincubation of positive serum samples with eye muscle and thyroid cell, but not other cell, monolayers. The reaction of a newly identified cytotoxic thyroid antibody with a shared epitope on eye muscle cells thus appears to be a possible mechanism for the development of ophthalmopathy in patients with Gh and, less often, HT.

Adolescent↗

The Republic of Singapore Navy's Scopoderm TTS study: results after 2,200 man-days at sea.

Most clinical trials investigating prevention of seasickness with transdermal scopolamine have been short-term, and little information regarding long-term use is available. We report here a double-blind trial conducted on board a flat-bottomed Republic of Singapore Navy vessel of 2,490 tons, sailing in the South China Sea. The trip lasted 26 d, but self-assessment by the 122 adult male participants (using a simplified scale quantifying the level of seasickness) was confined to the 18 d spent at sea. We found that the protection rate with transdermal scopolamine was 46-57%, with maximum benefits to inexperienced participants, during the early preadaptation phase, or in rough seas even after adaptation. Unwanted effects were few and generally minor. We concluded that the benefits of Scopoderm were worth exploiting even for long trips in moderate-to-rough seas.

Administration, Cutaneous↗

Mechanisms of immune damage in Graves' ophthalmopathy.

We have studied the role of immunologically mediated cytotoxicity in the orbital tissue damage of Graves' ophthalmopathy. Antibody-dependent cell-mediated cytotoxicity (ADCC) against eye muscle (EM) cells and orbital fibroblasts (OF) was demonstrated in a small proportion of patients, all of whom had severe, recent disease. Antibody-mediated (complement-dependent) cytotoxicity against OF was found in only a few patients. No patients showed lysis above background with EM targets. ADCC activity against OF was absorbed by preincubation of serum with thyroid cells, eye muscle cells, and orbital fibroblasts, as well as thyroid, eye muscle and orbital connective tissue membranes. Both EM and OF were able to express class II MHC HLA-DR antigens when stimulated by gamma interferon, phytohemagglutinin or activated T lymphocytes. DR-positive target cells were much more susceptible to lysis, in both ADCC and lymphocyte-mediated cytotoxicity, than DR negative cells. When DR-positive OF and EM were used as targets in ADCC assays, the degree of lysis determined as 51Cr release given by serum from patients with Graves' ophthalmopathy was enhanced, but only in those patients showing positive tests with DR-negative targets. Intrathyroidal T lymphocytes obtained from a patient with Graves' ophthalmopathy were more cytotoxic against DR-positive OF and EM than equal numbers of her peripheral blood T lymphocytes. Antibody-dependent cell-mediated cytotoxicity and lymphocyte-mediated cytotoxicity against orbital fibroblasts and eye muscle cells are thus associated with target cell HLA-DR antigen expression and are likely to be mechanisms for in vivo tissue damage in Graves' ophthalmopathy. The identity of the mononuclear cell subpopulation effecting cell-mediated cytotoxicity against orbital target cells, and the possible significance of reaction of cytotoxic antibodies against orbital, thyroid-shared antigens are unclear.

Adult↗

Antibody-dependent cell-mediated cytotoxicity against human eye muscle cells and orbital fibroblasts in Graves' ophthalmopathy--roles of class II MHC antigen expression and gamma-interferon action of effector and target cells.

We have studied the significance of antibody dependent cell-mediated cytotoxicity (ADCC) against human orbital fibroblasts (OF) and eye muscle (EM) cells in the pathogenesis of the orbital autoimmune reactions of Graves' ophthalmopathy (GO). Possible roles of Class II MHC antigen expression on the surface of orbital target cells and of gamma-interferon (gamma-IFN) modulation of ADCC were also studied. Both OF and EM expressed HLA-DR antigen when stimulated with gamma-IFN and phytohemagglutinin, but not spontaneously, and not by thyroid stimulating hormone or alpha-IFN. Intrathyroidal T cells from a patient with GO induced greater DR expression on both OF and EM cells than equal numbers of her peripheral blood T cells. gamma-IFN treated EM and OF were more susceptible to lysis in ADCC assays than untreated targets. gamma-IFN also enhanced lysis in ADCC assays by an effect on the killer cell population. On the other hand treatment with alpha-IFN, which is a potent inducer of Class I antigen expression, did not affect the susceptibility of target cells to lysis in ADCC. When sera from patients with GO were tested in ADCC, tests were positive (% specific lysis greater than mean + 2 s.d. for normals) in 10 of 20 patients with EM cells, but in only two of 25 with OF. The degree of killing of EM cells was significantly positively correlated to that of abdominal skeletal muscle cells and, to a lesser degree, normal thyroid cells, but not OF. In sera showing killing of EM cells and OF, ADCC activity against EM cells was absorbed by preincubation with EM and orbital connective tissue membranes but not thyroglobulin and, conversely, lysis of THY cells was absorbed by preincubation of positive sera on monolayers of THY and EM cells and OF, but not vascular endothelial (VE) cells. Finally, killing of 51Cr labelled EM cells was inhibited by addition of unlabelled ('cold') thyroid cells, EM cells and OF, but not VE cells. Our findings suggest that ADCC is likely to be an important mechanism for the eye muscle cell damage of GO, but not for the associated orbital connective tissue inflammation. Since ADCC is not MHC-restricted the enhanced lysis of HLA-DR positive target cells presumably reflects other effects of gamma-IFN treatment on both the killer cell population and the target cells.

Adolescent↗

Pregnancy and autoimmune thyroid disease.

Pregnancy has profound effects on the course of Graves' disease and Hashimoto's thyroiditis. Understanding of this interrelationship may clarify the role of the numerous immunologic gestational alterations that facilitate survival of the fetal allograft. Also, it should provide a more rational basis in the management of Graves' hyperthyroidism during pregnancy. Epidemiologic data indicate that screening for thyroid dysfunction appears justified in women in the postpartum period. The natural history of the postpartum thyroiditis syndrome remains to be fully evaluated, but the evidence indicates thyroid abnormalities can still be found in many patients several years after onset. Accordingly, the importance of follow-up cannot be overemphasized.

Female↗

Immunologically mediated cytotoxicity against human eye muscle cells in Graves' ophthalmopathy.

The possible roles of antibody-mediated complement-dependent cytotoxicity (AMC), antibody-dependent killer (K) cell-mediated cytotoxicity (ADCC), and spontaneous, natural killer (NK) cell-mediated cytotoxicity (NKC) against human eye muscle cells in the pathogenesis of Graves' ophthalmopathy were investigated, using as targets human eye muscle cells, by 51Cr release assays. AMC was not demonstrated in serum from any patient or normal subject. In ADCC assays, eye muscle cell lysis was significantly increased in serum from patients with Graves' ophthalmopathy compared to those with Graves' hyperthyroidism without eye disease and normal subjects. ADCC tests were positive (percent specific lysis greater than the upper limit of normal) in 5 of 13 patients with Graves' ophthalmopathy using serum diluted 1:48 and in 4 of 10 patients using serum diluted 1:6. There was no correlation between the extent of lysis of human eye muscle and that of human (abdominal) skeletal muscle and no difference between patients with Graves' ophthalmopathy and normal subjects in assays in which abdominal muscle cell targets were used. The degree of killing in ADCC tests was independent of the source of K cells, being similar in assays using effector cells from the patient, another patient, or a normal subject. ADCC activity was partially absorbed by thyroid, orbital connective tissue and eye muscle membranes, and eye muscle cells, but not by liver membranes of thyroglobulin. Four of 8 human monoclonal antibodies reactive with eye muscle membrane antigens were cytotoxic in ADCC assays. A noncytotoxic monoclonal antibody blocked the ADCC effect of serum from a patient with Graves' ophthalmopathy, while a cytotoxic monoclonal antibody enhanced killing. NKC against eye muscle cell targets was depressed in cells from hyperthyroid and euthyroid patients with Graves' ophthalmopathy compared to that in normal subjects. Demonstration of ADCC against human eye muscle cells in some patients with Graves' ophthalmopathy suggests that this may be a mechanism for the eye muscle cell damage characteristic of this disorder. Inability to demonstrate cytotoxicity in a greater proportion of patients may reflect the lack of specific criteria to identify patients with active eye muscle inflammation and the unsuitability of currently available tests for the detection of serum antibodies against eye muscle membrane antigens. The mechanism for depressed NK cell-mediated cytotoxicity against eye muscle cells in this disorder is not known.

Adult↗

Serum levels of pregnancy associated alpha 2-glycoprotein (alpha 2-PAG) during pregnancy in autoimmune thyroid disease: relationship to disease activity.

Serum concentrations of pregnancy associated alpha 2-glycoprotein (alpha 2-PAG) were measured serially by an enzyme linked immunosorbent assay during 24 pregnancies in 18 patients with Graves' disease and four with Hashimoto's thyroiditis. During each trimester, alpha 2-PAG levels were significantly higher than in normal pregnant controls, matched for week of gestation. Patients showing remission of disease activity had progressively higher alpha 2-PAG levels throughout pregnancy than those with active disease. The data support the idea that alpha 2-PAG may play an important role in inducing and maintaining the clinical remissions observed in some women with autoimmune thyroid disease during pregnancy.

Adult↗