Birth weight as a health outcome measure.
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Biomedical subjects
Publications and source records attributed to A White.
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Adrenal phaeochromocytoma rarely causes ectopic ACTH syndrome. We describe a 44-yr-old hypertensive woman who was Cushingoid and markedly pigmented. Laboratory studies indicated severe hypokalaemia, abnormal liver function tests, and random serum cortisols greater than 1660 nmol/L. Urinary catecholamines were markedly increased. An abdominal computed tomography scan showed a 4-cm left adrenal mass and an hypertrophied right adrenal. ACTH levels were elevated at 200 pmol/L, but ACTH precursors, which cross-react in the ACTH assay, were more highly elevated at 1625 pmol/L. The tumor cells cultured in vitro also secreted ACTH precursors, whereas ACTH levels were undetectable. Because the patient was highly pigmented, we measured circulating concentrations of alpha-MSH, which were undetectable and certainly insufficient to stimulate melanogenesis, suggesting that tumorderived ACTH precursors or ACTH were responsible for the pigmentation. A laparoscopic adrenalectomy resulted in remission of the Cushing's syndrome and dramatic reduction in the pigmentation. Before operation, treatment of the patient with metyrapone and replacement dexamethasone decreased cortisol from more than 1660 to less than 20 nmol/L. Surprisingly, this resulted in a decrease in ACTH precursors to 100 pmol/L and ACTH to 9.0 pmol/L. In vitro treatment of the tumor cells with dexamethasone for 24 or 40 h increased ACTH precursor secretion. In summary, this phaeochromocytoma causing Cushing's syndrome secreted primarily ACTH precursors, which seemed to cause the marked pigmentation. In vivo and in vitro evidence suggests that glucocorticoids induced ACTH precursor secretion.
A 26-year-old man was seen one day after developing a left facial palsy of unknown aetiology. He had previously had a left facial palsy at age 14 and a right facial palsy at 19, both with minimal residual paresis. Both his mother and grandmother have had facial palsies. The role of hereditary influences in idiopathic facial paralysis, as well as the treatment of this condition, is discussed.
This study is the first to provide direct observations of dyadic interactions with friends for preschool-aged disruptive children. Forty preschoolers (mean age 52 months) rated by parents as "hard to manage" on Goodman's (1997) Strengths and Difficulties Questionnaire (SDQ), as well as 40 control children (matched for age, gender, school, and ethnic background) were filmed for 20 minutes on two occasions playing with a teacher-nominated best friend. The videos were transcribed and coded for antisocial behaviour, displays of negative emotion, and empathic/prosocial responses to friend's distress. Individual differences in social behaviour were considered in relation to false-belief performance, affective perspective taking, and executive function skills (planning and inhibitory control). Compared with controls, the hard-to-manage group showed significantly higher rates of both antisocial behaviour and displays of negative emotion, as well as significantly lower rates of emphatic/prosocial responses. Across both groups combined, frequencies of angry and antisocial behaviours were related to poor executive control. Mental-state understanding was not significantly correlated with antisocial behaviour, emotion display, or empathy, suggesting that the interpersonal problems of young disruptive children owe more to failure of behavioural regulation than to problems in social understanding per se. However, given the relatively low power of the study, these findings require replication with a larger sample.
INTRODUCTION: Recent data about the use of complementary and alternative medicine (CAM) by the general population exist for Australia and the USA, but not for the UK. This study aimed at providing such data. DESIGN: Nationally representative random telephone survey. SETTING AND PARTICIPANTS: 1204 British adults were interviewed. RESULTS: 20% of the sample used CAM in the previous year. Herbalism, aromatherapy, homoeopathy, acupuncture/acupressure, massage and reflexology were the most popular treatment modalities. The main reasons for trying CAM were its perceived effectiveness, a positive inclination towards it, and its relaxing effects. On average, users spent 13.62 +/- 1.61 Pounds on CAM per month, which extrapolates to an annual expenditure of 1.6 billion Pounds for the whole nation. CONCLUSIONS: It is concluded that CAM is prevalent in the UK. Therefore, its scientific validation has become an ethical imperative.
This article describes a procedure for modification of the commercially prepared GeneScan 2500 size standard for allelotyping with large DNA fragments such as variable number tandem repeats (VNTRs). Here a procedure was used to adapt commercially available size standards for the sizing of the interleukin-6 (IL6) 3'VNTR, which has allele sizes ranging from 600 to 900 base pairs. The procedure involves inclusion of products from the target PCR reaction as additional size standards for use with the size standard and is therefore applicable to the sizing of any product with any commercial size standard. Initially alleles were sized by fluorescent cycle sequencing to give a true estimate of their size (base pairs). Subsequently, the major alleles were labeled with a pig-tailed ROX-dye-labeled primer and inserted into the standard range. Finally alleles were resized following PCR with an un-pig-tailed HEX labeled primer and the modified standard. Once the size standard is modified, stocks can be stored indefinitely and replenished by re-PCR of selected alleles using the ROX-labeled primer. Modification of this approach can be applied to the sizing of any product where it is thought that commercially available size standards are performing suboptimally. Modification of size standards in this way does not affect performance in size regions other than those for which the extra products are included.
Glucocorticoids act through the glucocorticoid receptor (GR) to enhance or repress transcription of glucocorticoid responsive genes depending on the promoter context and cellular background. The human GR primary transcript is alternatively spliced resulting in hGR alpha and hGR beta isoforms. Transactivation and transrepression are mediated by hGR alpha and while it has been demonstrated that hGR beta, can act as a dominant negative inhibitor of hGR alpha mediated transactivation, its effects on transrepression are not known. To investigate hGR beta actions, we used GR-deficient COS-7 and HEK-293 cells. When hGR alpha (0.5 microg 10(6) cells(-1)) was transfected into COS-7 cells dexamethasone (150 nM) inhibited TNF alpha (80 U ml(-1)) effects on a NF-kappaB responsive reporter gene by 40%. There was no evidence of a dominant negative effect when hGR beta (1-10 microg) was co-transfected with hGR alpha up to ratios of 10:1. Similarly hGR beta had no effect on hGR alpha inhibition of a phorbol ester stimulated Ap-1-responsive reporter gene in COS-7 or HEK-293 cells. In comparison, an apparent dominant negative effect of hGR beta on hGR alpha-mediated transactivation was found to be attributable to non-specific transcriptional squelching in COS-7 cells. In summary, the potential for hGR beta, to act as a dominant negative inhibitor of hGR alpha-mediated transactivation remains controversial, but our data suggest that hGR beta, was unable to act as a dominant negative inhibitor of either hGR alpha-mediated transrepression or transactivation in these promoter and cell contexts.
The magnetotelluric component of the Mantle Electromagnetic and Tomography (MELT) Experiment measured the electrical resistivity structure of the mantle beneath the fast-spreading southern East Pacific Rise (EPR). The data reveal an asymmetric resistivity structure, with lower resistivity to the west of the ridge. The uppermost 100 kilometers of mantle immediately to the east of the ridge is consistent with a dry olivine resistivity structure indicating a mantle depleted of melt and volatiles. Mantle resistivities to the west of the ridge are consistent with a low-melt fraction (about 1 to 2 percent interconnected melt) distributed over a broad region and extending to depths of about 150 kilometers. The asymmetry in resistivity structure may be the result of asymmetric spreading rates and a westward migration of the ridge axis and suggests distinct styles of melt formation and delivery in the mantle beneath the two plates.
The effects of the corticotropin-releasing factor (CRF) receptor antagonists, alpha-helical CRF-(9-41), [D-Phe12,Nle21,38, CalphaMe-Leu37]humanCRF-(12-41) (D-PheCRF-(12-41)) and astressin ([cyclo(30-33)[D-Phe12,Nle21,38,Glu30,Lys33]h umanCRF-(12-41) upon hypophagic and motor activation response to human/ratCRF (h/rCRF) were investigated. All three antagonists (100 microg intracerebroventricular (i.c.v.)) blocked the effects of h/rCRF (1 microg i.c.v.) upon food intake and body weight change in food-deprived rats. In contrast, alpha-helical CRF-(9-41) and astressin (both at 100 microg i.c.v., but not lower doses), but not D-PheCRF-(12-41) (up to 100 microg i.c.v.), blocked h/rCRF (0.3 microg i.c.v.)-induced motor activation in rats in a familiar environment. The ability of D-PheCRF-(12-41) to block CRF-induced hypophagia, but not motor activation, suggests a selective action of this antagonist upon the behavioural effects of centrally administered h/rCRF.
OBJECTIVE: Sex steroid regulation of the insulin-like growth factor axis is a subject of contention. We examined the effect of combined oral contraceptives and investigated the cyclic variations in the insulin-like growth factor axis. STUDY DESIGN: Fasting blood samples were taken from 9 women receiving oral contraceptives, 10 women receiving no medication, and 10 male subjects. RESULTS: In women receiving oral contraceptives, insulin-like growth factor binding protein 1 remained highly phosphorylated and levels were acutely increased by sex steroid treatment (305 +/- 110 microg/L on day 14 of the cycle [medication phase] vs 118 +/- 70 microg/L during the medication-free period, P <.03). In women receiving no medication, insulin-like growth factor binding protein 1 levels were significantly lower (69 +/- 50 microg/L on day 14 of the menstrual cycle, P <.001) and varied cyclically, with a rise in the late-secretory phase that coincided with the appearance of nonphosphorylated and less phosphorylated insulin-like growth factor binding protein 1 isoforms. Compared with those in untreated women and in men, insulin-like growth factor I levels were decreased in women receiving oral contraceptives (405 +/- 104 ng/mL in untreated women and 330 +/- 28 ng/mL in men vs 287 +/- 73 ng/mL in women receiving oral contraceptives, P <.004). Oral contraceptive use had no effect on insulin-like growth factor II levels, and neither insulin-like growth factor I nor insulin-like growth factor II showed cyclic variation. CONCLUSION: The bioavailability of insulin-like growth factor I is reduced in users of oral contraceptives. This may contribute to the metabolic changes observed in such subjects.
Invasive meningococcal disease (IMD) is thought to occur within a few days of pharyngeal acquisition of Neisseria meningitidis. During a longitudinal study of carriage and acquisition among 2453 first-year undergraduates we identified a male student from whom N. lactamica was isolated in October 1997 followed by N. meningitidis in December 1997. In mid-January 1998 this student suffered a mild episode of IMD (meningitis) during which N. meningitidis was isolated from his CSF. The meningococcus carried in December 1997 was phenotypically and genotypically indistinguishable from the invading organism, suggesting the possibility that the organism may have been carried for 7 weeks prior to the onset of invasive disease. Further studies are needed to assess more accurately the range of asymptomatic carriage prior to disease onset.
BACKGROUND: Reported operative mortality and survival rates following total pelvic exenteration (TPE) for recurrent pelvic neoplasia are now as good as those for many primary treatments. The currently accepted primary treatments for these tumours are, however, still either radiotherapy alone or radiotherapy and chemotherapy. The primary aim of this study was to evaluate the safety and tolerability of TPE and secondarily to ascertain survival after TPE. METHODS: This was a phase II study of 50 patients with locally advanced pelvic tumours who underwent TPE. RESULTS: Thirty-two patients (64 per cent) underwent TPE for recurrent carcinoma of the cervix, seven (14 per cent) for rectal cancer, three (6 per cent) for vulval carcinoma, three (6 per cent) for vaginal carcinoma, two (4 per cent) for prostate cancer and three (6 per cent) for other tumours. The 30-day mortality rate was 8 per cent with an in-hospital mortality rate of 16 per cent. The crude morbidity rate was 62 per cent, with 23 patients (46 per cent) having grade III or IV toxicity. A complete response was achieved in 63 per cent and a partial response in 37 per cent of patients. The overall median survival time was 86 weeks; it was 111 weeks in patients in whom a complete response was achieved. CONCLUSION: The survival and operative mortality rates that are now attainable with TPE are comparable to those achieved with chemoradiotherapy in advanced pelvic neoplasia. TPE should no longer be reserved for salvage therapy and should perhaps be compared with chemoradiotherapy as first-line treatment in a phase III randomized trial in patients with these tumours.
OBJECTIVE: To assess whether there is evidence that acupuncture is effective in the treatment of recurrent headaches. DESIGN: Systematic review. STUDY SELECTION: Randomized or quasi-randomized clinical trials comparing acupuncture with any type of control intervention for the treatment of recurrent headaches. DATA SOURCES: Electronic databases (Medline, Embase, Cochrane Field for Complementary Medicine, Cochrane Controlled Trials Register), personal communications and bibliographies. DATA COLLECTION AND ANALYSIS: Information on patients, interventions, methods, and results were extracted by at least two independent reviewers using a pretested form. A pooled estimate of the responder rate ratio (responder rate in treatment group/responder rate in control group) was calculated as a crude indicator of trial results as meta-analysis of more specific outcome data was impossible due to heterogeneity and insufficient reporting. RESULTS: Twenty-two trials, including a total of 1042 patients (median 36, range 10-150), met the inclusion criteria. Fifteen trials were in migraine patients, six in tension-headache patients, and in one trial patients with various headaches were included. The majority of the 14 trials comparing true and sham acupuncture showed at least a trend in favor of true acupuncture. The pooled responder rate ratio was 1.53 (95% confidence interval 1.11 to 2.11). The eight trials comparing acupuncture and other treatment forms had contradictory results. CONCLUSIONS: Overall, the existing evidence suggests that acupuncture has a role in the treatment of recurrent headaches. However, the quality and amount of evidence is not fully convincing. There is urgent need for well-planned, large-scale studies to assess effectiveness and efficiency of acupuncture under real life conditions.
Multiorgan failure (MOF) based on septic processes is very common but prognostically an extremely severe disease that has to be treated exclusively under intensive care conditions. Extracorporeal blood purification (ECBP) using specific and efficient systems such as the microspheres based detoxification system (MDS) (Artif Organs 1996;20:420) could improve significantly the situation of MOF in terms of the efficient removal of endotoxins as well as key mediators such as tumor necrosis factor alpha (TNF alpha). The purpose of the study was to test the effectiveness of endotoxin and cytokine removal to blunt cellular response. In terms of the in vitro principle methodology, isolated peripheral blood mononuclear cells (PBMC) were incubated with endotoxins and a selective endotoxin adsorbent, which was added at various times (immediately or 30, 60, 120, 240, or 360 min) after the onset of incubation. TNF alpha release of monocytes was measured following a standard procedure after 20 h. Human TNF alpha was incubated with cultured human endothelial cells with and without a specific TNF alpha adsorbent (polyclonal antibodies coated on polystyrene particles). The results showed that after the initial addition of endotoxins, the activation of monocytes can be stopped within 120 min by addition of endotoxin adsorbents. In addition, specific TNF alpha adsorbents are able to prevent intercellular adhesion molecule 1 (ICAM-1) expression of endothelial cells, therefore avoiding activation of endothelial cells. In conclusion, cell culture models are suitable to simulate cell interaction in MOF. Specific adsorbents are able to reduce or block pathophysiologically relevant cell interactions, and the time frame for effective ECBP seems to be very short, and therefore, efficiency must be high.
A literature search revealed no systematic enquiry into the experience of humour by nurses in the intensive care setting, suggesting that there was a need for such studies (Astedt-Kurki & Liukkonen 1994). This phenomenological study was undertaken using an interpretive human science approach of phenomenology grounded in the hermeneutics of Heidegger. The task was to investigate and describe the concept of humour in an intensive care unit (ICU) from an inductive-descriptive perspective, seeking to identify the essence of the phenomenon through an accurate description of the lived experience of humour. A sample of eight nurses with at least one year's intensive care experience was randomly selected. Semi-structured interviews were conducted, audiotaped, transcribed into text, checked for transcription errors, and returned to participants for checking to ensure reliability and validity. Main core themes were identified and categorized, then Colaizzi's seven steps were used for analysis. Themes and categories identified in the collected data were rich and varied, allowing for lengthy discussions on thoughts and experiences. The study revealed a rich experience of humour in the ICU, suggesting that humour is central to nursing, and therefore worthy of deeper analysis using the same methodology.
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The sensitivity and specificity of recombinant open reading frame 5 products used in the Western blotting assay for confirmation of porcine reproductive and respiratory syndrome virus (PRRSV) serologic status were evaluated. The recombinant antigen-based assays were specifically compared with a commercial enzyme-linked immunosorbent assay (ELISA) for PRRSV antibodies using 1) PRRSV antibody-negative reference sera (n = 30), 2) naturally infected pig sera (n = 40), 3) sequential sera obtained from 24 experimentally infected pigs, and 4) sera submitted to 3 state diagnostic laboratories (n = 200). The recombinant antigen assay yielded an average increased sensitivity of 10% over the commercial PRRSV ELISA. The negative controls (group 1 sera) showed no difference between the 2 assays. This comparison confirmed that the recombinant antigen-specific assay was more sensitive than the commercial ELISA and is well suited for routine confirmation of the presence of PRRSV antibodies.