Laser stapedotomy. A new method of correcting deafness.
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Deafness↗
Biomedical subjects
S Cunningham
Publications and source records attributed to S Cunningham.
Human immunodeficiency virus type 1 envelope gene structure and diversity in vivo and after cocultivation in vitro.
Nested-primer polymerase chain reaction (PCR) has been applied to the molecular cloning of 4.6-kb half-genome fragments of human immunodeficiency virus type 1 (HIV-1) taken directly from the peripheral blood mononuclear cells (PBMC) of an individual with neurological symptoms of HIV-1 infection. In a similar manner, gp120-coding portions of the envelope gene were cloned after PBMC from the same blood sample were cocultivated with uninfected PBMC for 28 days. The complete 1.6-kb nucleotide sequence of the gp120 gene was determined from each of 35 clones examined. Two of 13 (15%) PBMC-derived gp120 genes and 3 of 22 (14%) coculture-derived gp120 genes were defective as a result of frameshifts and an in-frame stop codon(s). Mean diversity between individual gp120-coding sequences in PBMC was fivefold greater (3.24%) than after coculture (0.65%). A predominant sequence of "strain" was found after coculture that was distinct from the diverse viral genotypes detected in vivo and therefore was selectively amplified during in vitro propagation. Multiple distinct third variable (V3) regions encoding the principal neutralizing domain of the envelope protein were detected in PBMC-derived genes, suggesting the presence of immunologic diversity of HIV env genes in vivo not reflected in the cocultured virus sample. The large size of the HIV fragments generated in this study will permit analysis of the diversity of immunologic reactivity, gene function, and pathogenicity of HIV genomes present within infected individuals, including the functional significance of the loss of diversity that occurs upon coculture.
Acquired Immunodeficiency Syndrome↗
Occupational therapy entry-level program applicants: a survey of northwest schools.
Recruitment of occupational therapy students requires both expansion and broadening of ethnic, cultural, age, sex, and geographic distribution. Information used to guide recruitment activities can be limited, quickly outdated, and regionally nonspecific. Applicants to all entry-level programs in the Northwest were surveyed to assess trends that could influence recruitment practices. One hundred thirty-five (82.8%) of the 163 applicants surveyed responded to a questionnaire that probed for sources of exposure to occupational therapy, career goals, and educational preferences. Applicants indicated having an initial interest in allied health or education fields, yet only 36% began college with occupational therapy education in mind. Volunteer or work experience in specific practice settings was identified by approximately 80% of the applicants as an influence in seeking an education in occupational therapy. Career influences, goals, and educational program preferences did not differ among applicants based on age, residential background, grades, or previous degree. An absence of applicants of ethnic minority allows limited application of findings to these targeted groups.
Adult↗
The epidemiologic basis of coronary disease prevention.
With a knowledge of the epidemiologic basis underlying the risk factors for CHD, the nurse can improve the quality of care offered to clients. By collecting information during assessment, the nurse can identify persons at increased risk for CHD. Information about the nonmodifiable risk factors can be used to assist in determining the amount of emphasis to place on borderline levels of the modifiable risk factors. As risk factor data are collected, the nurse can also explain the nature of the risk factor-CHD relationship to the client and family, thus teaching them as well as demonstrating that nursing practice is data based. When the health care team has decided on the focus of risk factor modification, the nurse will know about clinical trials that underlie the treatment plan or else will be able to explain that there are still areas of incomplete knowledge.
Cholesterol↗
Systemic lupus erythematosus presenting as an intracranial bleed.
A previously healthy 12-year-old girl presented with fever and mental status changes without focal neurologic deficit. A CBC and computed tomography scan revealed thrombocytopenia and an intracranial bleed. Further laboratory studies were consistent with systemic lupus erythematosus. This case emphasizes the need to maintain a high index of suspicion for atypical presentations of an uncommon childhood illness.
Cerebral Hemorrhage↗
Chemical control of interstrain competition for soybean nodulation by Bradyrhizobium japonicum.
Previous research has shown that a significant limitation to the agricultural use of improved rhizobial inoculant strains is competition from the indigenous soil population. In this work, we sought to test whether chemical inhibitors of flavonoid-induced nod gene expression in Bradyrhizobium japonicum could be identified and utilized to affect interstrain competition for nodulation of soybeans. Approximately 1,000 structural and functional analogs of the known, natural inducers of nod gene expression were tested on six strains of B. japonicum containing a nodY-lacZ fusion. We successfully identified effective inhibitors of nodY expression. The addition of the inhibitor 7-hydroxy-5-methylflavone significantly inhibited nodulation by a sensitive strain and could be used to effectively manipulate the competition between strains for soybean nodulation. However, this work also uncovered significant limitations for the practical use of this methodology. For example, despite the almost universal induction response to the identified natural inducers, there was a wide variability among strains in their response to any specific inhibitor. Given this unexpected variability, the cost of registration of an agronomic chemical, and the potential for the development of resistant field populations, it is unlikely that chemical inhibitors can be successfully applied to a field situation.
Benzoates↗
Diagnosis under random conditions of all disorders of the renin-angiotensin-aldosterone axis, including primary hyperaldosteronism.
Theoretically, the relationship between plasma aldosterone (PA) and PRA in normal subjects under random conditions should differ from that in patients with primary hyperaldosteronism or primary adrenal failure, but should be similar to that in patients with secondary hyperaldosteronism or hyporeninemic hypoaldosteronism. PA, expressed as a function of PRA, the PA/PRA ratio, provides an index of adrenal sensitivity in normal subjects under routine conditions. The random PA/PRA ratios in patients with primary adrenal disorders did not overlap with those in normal subjects, patients with secondary adrenal disorders, hypertensive subjects, or other patients. A single elevated PA/PRA ratio, i.e. more than 920, associated with elevated PA in 4 patients or normal PA in 6 patients indicated primary hyperaldosteronism in 10 patients. However, 5 of 17 patients with chronic renal failure had elevated PA/PRA ratios, but did not have primary hyperaldosteronism. All 14 patients with secondary hyperaldosteronism had elevated PA associated with normal PA/PRA ratios. A single PA/PRA ratio of less than 28 associated with low PA in 18 patients and a normal PA in 1 patient indicated primary adrenal insufficiency, while a low PA associated with a normal PA/PRA ratio indicated hyporeninemic hypoaldosteronism in 7 patients. Fifty-nine patients with nonadrenal disorders other than renal failure had normal PA and PA/PRA ratios. Therefore, with the exception of patients with advanced renal failure, only a single blood sample is required to establish all diagnoses of disorders of the renin-angiotensin-aldosterone axis under random conditions.
Biomarkers↗
Sex steroids, adiposity and smoking in the pathogenesis of idiopathic hirsutism and polycystic ovary syndrome.
Hyperestronemia may be central to the development of polycystic ovary syndrome. The present study was designed to examine whether increased availability of androstenedione or increased aromatase closely associated with adiposity, plays the dominant role in the development of hyperestronemia. We measured plasma androstenedione, estrone and the estrone/androstenedione ratio (an indirect index of peripheral aromatase activity), in 141 patients with idiopathic hirsutism and in 88 patients with polycystic ovary syndrome. Estrone levels were higher in polycystic ovary syndrome, 250.4 +/- 129 (mean +/- standard deviation) than in idiopathic hirsutism, 210.6 +/- 119 pmol/l, p less than 0.05. Plasma androstenedione levels were higher in polycystic ovary syndrome, 8.24 +/- 3.5, than in idiopathic hirsutism, 7.1 +/- 1.7 nmol/l, p less than 0.0025. However, the estrone/androstenedione ratio was similar in the two groups. In all patients who smoked, androstenedione was higher, 8.14 +/- 3.22 than in nonsmokers, 6.99 +/- 2.96 nmol/l, p less than 0.005. Smokers had a lower body mass index, 23.9 +/- 2.3, than non-smokers 25.6 +/- 4.8 kg/m2, p less than 0.025. However, estrone levels were similar in smokers and in non-smokers. These data indicate that elevated estrone is more closely related to increased availability of androstenedione than to increased aromatase activity. While cigarette smoking appears to increase androstenedione levels, it may inhibit aromatase activity either directly or indirectly because of an associated reduction in adiposity. However, since the relative frequency of polycystic ovary syndrome and idiopathic hirsutism was similar in smokers and non-smokers, smoking did not appear to reduce estrone bioactivity as had been claimed.
Adrenal Glands↗
Genetic complementation in cystic fibrosis pancreatic cells by somatic cell fusion.
The biochemical defect that underlies the genetic disorder cystic fibrosis (CF) has been proposed to involve an altered regulation of epithelial Cl- permeability by agents such as adenosine 3',5'-cyclic monophosphate (cAMP). We report here the successful complementation of this functional defect achieved by using the technique of somatic cell fusion to introduce the normal CF allele into mutant cells. CF epithelial cells were fused with transfectant mouse fibroblasts that contain the normal human gene. The resulting heterokaryons were examined for restoration of cAMP-activated Cl- transport using an optical assay of Cl- permeability. Our results provide direct evidence for the involvement of the protein product of the normal CF allele in modulating epithelial Cl- permeability.
Animals↗
Steroidogenesis in an estrogen-producing adrenal tumor in a young woman: comparison with steroid profiles associated with cortisol- and androgen-producing tumors.
There is only one previous report of an estrogen-secreting adrenal tumor occurring in a woman during reproductive years. Our patient presented with mild hirsutism associated with menstrual bleeding every 3-6 weeks. The occurrence of apparently intermenstrual bleeding prompted an evaluation of estrogen levels. Markedly elevated plasma estrone levels were found (860-2305 pmol/L; normal, 50-340). Lesser relative elevations in 11-deoxycortisol and androstenedione were noted. Computed tomographic scanning of the adrenal glands identified a large tumor, which was subsequently resected. Estrone levels fell to 120 pmol/L, and all other abnormalities were corrected. Eighteen months after adrenalectomy, ovulation occurred regularly, and steroid levels were entirely normal. Steroid production in a cell suspension made from tissue obtained from the 190-g tumor was compared with that occurring in normal human adrenal cells. The production of estrone by the tumor cells was 40-fold greater than that by normal adrenal cells. There was also a mild excess of 11-deoxycortisol produced by tumor cells, but the tumor cells were less than 50% as efficient as normal cells in producing cortisol, dehydroepiandrosterone, androstenedione, testosterone, and dehydroepiandrosterone sulfate. Examination of the steroid profile in plasma occurring in three other patients with adrenal tumors reveals that while elevations in estrone occur frequently, this is usually due to the peripheral conversion of very high levels of androstenedione. Estrone, androstenedione, and 11-deoxycortisol plasma levels were elevated in all four patients; dehydroepiandrosterone sulfate was elevated in only two of four patients. After resection of one of these tumors, all steroid levels remained normal despite the occurrence of extensive metastases. These observations confirm the difficulty of making a diagnosis of estrogen excess in a woman during reproductive years because of the paucity of physical signs. The acquisition of aromatase activity was clearly demonstrated by tumor cells from our patient in vitro. Elevated plasma concentrations of estrone, androstenedione, and 11-deoxycortisol provide useful markers for adrenal tumors, but no one steroid can be relied upon in all tumors, and metastases may lack the steroidogenic capabilities of the primary tumor.
Adrenal Gland Neoplasms↗
Office management of neurologic emergencies.
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Brain Diseases↗
Activation and differentiation antigen expression in B-cell non-Hodgkin's lymphoma.
In an attempt to establish whether extended immuno-phenotyping allows more accurate definition of subgroups of B-cell non-Hodgkin's lymphoma (NHL) we have stained a series of 145 cases with a large panel of monoclonal antibodies that recognize B-cell differentiation and activation antigens. No antigen was expressed by all cases. The B-cell histogenesis in many cases could be confirmed only by using a panel of immunoglobulin and pan B-cell markers. There was marked phenotypic heterogeneity within and between major groups of B-cell NHL as delineated by the Kiel classification although the differentiation antigens CD5 (lymphocytic and centrocytic NHL) and OKT10 (plasma cell tumours) were more often expressed by certain morphological groups. The activation antigens 4F2 and transferrin receptor were expressed more strongly and more often by high grade NHL but other activation antigens (CD23 and CD25) were not more frequently associated with these tumours. Extended phenotyping may be of value in improving the understanding of biological abnormalities and processes involved in B-cell NHL, but we conclude that a limited panel of markers (CD3, CD5, CD22, CD45, IgM, kappa, and lambda) should be sufficient for routine diagnosis and classification of most cases.
Antigens, Differentiation, B-Lymphocyte↗
Energy expenditure in normal and diabetic man: the role of brown adipose tissue.
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Adipose Tissue, Brown↗
From the National SSPE registry.
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Humans↗
Mechanisms of thermogenesis in brown adipose tissue.
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Adipose Tissue, Brown↗
Evaluation of an aldosterone radioimmunoassay: the renin-angiotensin-aldosterone axis as a function of sex and age.
A highly specific radioimmunoassay for aldosterone in plasma has been developed utilising extraction from plasma into dichloromethane, an antiserum raised to aldosterone-3-carboxy-methyloxime-BSA and a radio-iodinated derivative of aldosterone. The plasma values obtained after only extraction correlated very well with the results following chromatography over celite. The within- and between-batch variations for plasma pools ranged between 5 and 15%. The range obtained, 100-1806 pmol/L for 96 random upright subjects, was comparable to others reported. Measurement of plasma aldosterone and plasma renin activity in these subjects showed that both these parameters are higher in subjects under 40 years of age than in those over 40. In addition, plasma aldosterone levels are higher in women than in men even though their plasma renin activity levels are similar. The plasma aldosterone/renin activity ratios which provide an index of adrenal sensitivity to stimulation, are lower in men than in women. The findings in this study suggest that higher aldosterone levels in younger subjects are associated with greater stimulation of the adrenals than in older subjects and that the adrenal is more sensitive in women than in men.
Age Factors↗
Adrenal abnormalities in polycystic ovary syndrome.
This study was undertaken to examine the role of adrenal androgen excess in the pathogenesis of polycystic ovary syndrome (PCOS) and, if such was present, to assess its reversibility using dexamethasone given in physiological dosage at night. Mean plasma testosterone (T), T/sex-hormone binding globulin (T/SHBG) ratio, androstenedione, and 17-OH-progesterone levels were elevated in the 19 patients studied. Plasma estrone values were elevated, whereas estradiol levels were normal. Plasma FSH was decreased and LH responsiveness to LHRH was exaggerated. Metyrapone, an 11-hydroxylase inhibitor, was administered at 2400 h to induce hypocortisolemia and compensatory ACTH secretion so that adrenal androgen and glucocorticoid responsiveness to endogenous stimulation could be examined. Plasma T, androstenedione, and 11-deoxycortisol responses to metyrapone were excessive in PCOS patients, thus indicating a specific adrenal abnormality. After 3 months treatment with dexamethasone, 0.5 mg at night, mean plasma T/SHBG and androstenedione declined to normal, and mean plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate declined to below normal. The mean estrone value was slightly lower during dexamethasone. Plasma LH responsiveness to LHRH was no longer significantly different from normal, but FSH was suppressed. During treatment androgen responsiveness to metyrapone stimulation was normal, whereas 11-deoxycortisol responsiveness was suppressed. Fifteen patients completed 3 months of treatment with dexamethasone. Of these, 10 resumed regular menstruation. The latter group had suppression of plasma T, T/SHBG, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate. Only plasma androstenedione fell significantly in the remainder. These observations support the hypothesis that, in at least some patients, PCOS develops in response to abnormal gonadotropin secretion induced by hyperestronemia occurring as a consequence of excessive adrenal androgen secretion.
17-alpha-Hydroxyprogesterone↗
The predictive validity of the functional capacities evaluation.
This study tested the predictive validity of the Functional Capacities Evaluation (FCE), which included the following three components: a Medical History Review, a Client Activity Interview, and the Smith Physical Capacities Evaluation (SMITH-PCE) as the performance component. The FCE is used in conjunction with the Physical Demands and Environmental Conditions specified by the U.S. Department of Labor to predict a subject's ability to return to work. The study used a random sample of 52 subjects. An employment questionnaire served as a criterion measure of predictive validity. The data from the questionnaires were compared with predictions from the evaluations, and a lambdab test was applied to the data. Results suggested that for the sample analyzed, trained registered occupational therapists could use the FCE to predict a client's ability to return to work more accurately. The study was limited in that the sample used was drawn from clients seen in only one private practice and that only 42% of the questionnaires were returned.
Adult↗