Voice of a stranger.
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Biomedical subjects
Publications and source records attributed to S Cunningham.
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OBJECTIVE: A number of studies have suggested that both primary (Addison's disease) and secondary adrenal failure may be caused by idiopathic haemochromatosis. There is little information on mineralocorticoid secretion. We have assessed the mineralocorticoid and glucocorticoid status of patients with idiopathic haemochromatosis. DESIGN: Cross-sectional study. PATIENTS: Eighteen males and one female with confirmed idiopathic haemochromatosis were investigated. Seven of the subjects had hepatic cirrhosis and three had hypogonadotrophic hypogonadism. MEASUREMENTS: A short Synacthen (tetracosactrin) test was undertaken in addition to an overnight metyrapone test and an insulin stress test. In addition, plasma aldosterone (PA) and plasma renin activity (PRA) were measured in a group of patients in the basal state and again in the upright position. RESULTS: The short Synacthen test, overnight metyrapone test and insulin stress test were normal in all subjects. The PA, PRA, and PA/PRA ratios in the upright position were not significantly different in the patients with idiopathic haemochromatosis compared to control subjects. CONCLUSION: In this patient population, no abnormality of either the pituitary adrenal axis or mineralocorticoid status was detected. Adrenocortical dysfunction is likely to be exceptionally rare in idiopathic haemochromatosis.
There has been considerable controversy as to whether oral lichen planus (LP) has a premalignant potential. This study retrospectively examined the records of 241 British patients with histologically confirmed LP seen during the 10-year period 1982-92. Nine patients (3.7%) were known to have developed well-differentiated invasive carcinoma or carcinoma in situ in an area of LP. Most carcinomas at presentation were in areas of atrophic and/or erosive LP, 6 were in patients older than 65 years, and 6 were on the tongue. The results support a small but clinically important premalignant potential for LP.
Using a computerised physiological monitoring system a cyclical variation in blood pressure (waves), with associated changes in heart rate and transcutaneous oxygen, was observed. Twenty five episodes were seen in 10 neonates, with a median gestation of 33 weeks (range 28-42 weeks). Eight neonates had an asphyxial injury. Blood pressure waves had a mean (SD) amplitude of 11.6 (5.6) mm Hg with a mean wavelength of 9.0 (5.2) minutes. Both amplitude and frequency were independent of gestation. In neonates of less than 34 weeks an inverse phase relation existed between heart rate and blood pressure waves (blood pressure rose as heart rate fell); in infants with a gestation greater than 34 weeks a direct phase relationship occurred (blood pressure and heart rate rose together). It is postulated that hypertensive blood pressure waves may cause or exacerbate cerebral pathology in neonates with a pressure passive cerebral circulation.
The skin temperature in the right and left iliac fossae was recorded in 100 patients who were referred with a provisional diagnosis of acute appendicitis. This was not found to be a reliable aid in diagnosis of acute appendicitis nor an indicator to the need for surgery in patients with right iliac fossa pain.
A premature baby born up to four months early is a fragile patient dependent on intensive care. The body systems are physiologically immature and so tolerate stress badly. The tendency of these infants to rapidly deteriorate, has led us to use a cotside computer monitoring system which displays physiological trends. Information from standard neonatal monitors is accessed by individual cotside PC's linked to a central network server and Doctors terminal. Trend graphs can be easily manipulated, displaying from 7 minutes to 3 days of physiological information on a single screen. Pathology may be observed in real time as it occurs. The system has 3 main areas of use, (a) as a real time clinical aid to patient management, e.g. apnoea of the newborn; (b) as a research tool, demonstrating the effects of procedures on physiology; (c) for educating members of staff about how physiological events develop. Data is saved for the whole of each neonates intensive care stay. Assessment of staff and parent attitudes by questionnaire have been favourable.
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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.
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.
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.
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.
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.
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.
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.
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.
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.
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