Public health: water pressure.
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Alzheimer Disease↗
Biomedical subjects
J Wright
Publications and source records attributed to J Wright.
Identification of lysine residues required for signal-induced ubiquitination and degradation of I kappa B-alpha in vivo.
Activation of transcription factor NF-kappaB involves signal-induced degradation of the protein inhibitor IkappaB-alpha and release of NF-kappaB which translocates to the nucleus where it influences transcription of responsive genes. Although multiple regions of IkappaB-alpha are involved in this process, the N-terminal region of the protein has been identified as a regulatory region that is required for signal induced phosphorylation and degradation. The sensitivity of IkappaB-alpha degradation to peptide aldehydes which inhibit components of the proteasome and the detection of ubiquitinated forms of IkappaB-alpha indicate that IkappaB-alpha is degraded by the ubiquitin-proteasome pathway. To identify lysine residues that represent the sites of ubiquitin addition, a series of lysine to arginine mutations were introduced into IkappaB-alpha and the mutant proteins tested for their ability to function in vivo. Exposure of COS7 cells, cotransfected with IkappaB-alpha and a TNF-responsive NF-kappaB reporter gene, resulted in stimulation of reporter activity as a consequence of IkappaB-alpha degradation. In contrast, this effect was drastically reduced when an IkappaKB-alpha mutant carrying serine to alanine changes at amino-acids, 32 and 36, which blocks both signal-induced phosphorylation and ubiquitin conjugation of the protein, was co-transfected with the reporter gene. Likewise, a mutant form of IkappaB-alpha containing lysine to arginine changes at positions 21 and 22 (K21R, K22R) severely reduces TNF-induced activation of the NF-kappaB-dependent reporter gene. Examination of the metabolism of mutant IkappaB-alpha molecules reveals that, while the K21R, K22R mutant inhibits the DNA-binding activity of NF-kappaB and undergoes signal induced phosphorylation, it is neither ubiquitinated nor degraded in response to TNF. Thus, it is likely that after signal-induced phosphorylation Of IkappaB-alpha on serine residues 32 and 36, lysine residues 21 and 22 are major sites of ubiquitin ligation which target the protein for rapid degradation by the proteasome.
Amino Acid Sequence↗
Primary care out of hours. Emergency referral letters from deputising doctors need to be improved.
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Communication↗
Regulation of metallothionein in teleosts: induction of MTmRNA and protein by cadmium in hepatic and extrahepatic tissues of a marine flatfish, the turbot (Scophthalmus maximus).
Synthesis of the heavy metal-binding protein metallothionein (MT) was determined in the major organs of accumulation of Cd (liver, kidney and gills) of a marine flatfish, the turbot, after intraperitoneal (i.p.) administration of varying doses of Cd. Synthesis of MTmRNA and MT were linearly related to dose only at low Cd dosages (up to ca. 100 micrograms Cd/kg). Induction of MTmRNA was rapid, peaking 1-2 days after Cd administration in gills and kidneys, at 4 days in liver. In all three tissues, at low doses of Cd, MTmRNA levels declined with an apparent half life of 5-7 days and for a given dose of Cd, similar MTmRNA concentrations were attained. Induction of MT levels temporally followed that of MTmRNA. Steady state levels of MT were attained more quickly at a low dose of Cd. At acute Cd doses of > 200 micrograms Cd/kg, MT gene transcription and protein translation appeared to be progressively reduced, inferring that the rate of MT synthesis was limiting due to cytotoxicity of the high acute Cd dosage. In contrast to MTmRNA levels which were induced to similar levels in the three tissues, MT levels decreased in the order liver > kidneys > gills implying differences in translational processes.
Amino Acid Sequence↗
Two years of school injuries in a Scottish education sub-division.
Injuries sustained in schools account for 20-30% of all accident and emergency attendances in school age children. Little information has been available on the epidemiology of school accidents in the United Kingdom. Two years of routine school incident reports were analysed from Renfrew Sub-Region, an area with a school roll of 55,521 children attending 135 schools. Schools returned 1,660 report forms in the two year period, of which 1,440 referred to injuries to school children. The peak incidence of injuries was in the 10-12 year age group. The male:female ratio was 1.37:1. Cuts/ laceration and fractures were the commonest diagnoses reported for both Primary and Secondary Schools. Injuries to face and features were commonest in Primary, and upper limb injuries in Secondary Schools. Uncontrolled areas, e.g. playgrounds, stairways and corridors were the most frequent places of occurrence in Primary Schools (Relative Risk 5.24, 95% C.I. 3.28-8.35). Report accuracy was assessed by comparing one year of school reports in a Local Government District to records in the local District General Hospital. This identified 156 children who had attended hospital as the result of a school accident. Schools overestimated the number of fractures by 27%, but where schools had not provided a diagnosis, 15.4% were identified as fractures in hospital records. Each child seen at the hospital received an average of 2.1 X-rays. Nine children underwent manipulations under general anaesthetic. Seventeen children were admitted to hospital, and the group required 103 outpatient follow-up appointments.
Adolescent↗
Recurrent bacterial meningitis in adults: a case series.
Recurrent bacterial meningitis is rare and most commonly associated with an anatomical defect. We report on four adult cases that presented within a 13 month period. Anatomical or immunological abnormalities were found in three of the cases. Thorough investigations for an underlying cause should be carried out before the diagnosis of a chance recurrence is made.
Adolescent↗
"Fast tracking" patients in an urban pediatric emergency department.
Modern health care reform emphasizes efficient resource and facility management and the need to develop strategies to direct patients with lower-acuity concerns away from the relatively cost-inefficient full-service pediatric emergency department (ED). This study examined a pediatric fast track system for triage accuracy and turnaround times. Egleston Children's Hospital is a regional, urban, tertiary-care academic center which is a major teaching affiliate of Emory University School of Medicine. The pediatric ED has an annual census of more than 30,000 patient encounters. During the 9-month period from December 1993 through August 1994, 2,243 lower-acuity patients were evaluated in the fast track section of the ED. Patients assigned to the fast track system maintained a quicker turnaround time than the aggregate of all patients seen in the ED (107 [95% CI 0, 245] minutes versus 149 [95% CI 0, 341] minutes, P < .01). Their total turnaround time was also less than that for patients with similar acuity levels seen during the hours that the fast track system was not in operation (120 [95% CI 0, 300 minutes], P < .01). Only 63 of the 2,243 (2.8%) patients assigned to fast track were found to have higher acuity levels than suspected at initial triage. In all cases they were appropriately cared for in the fast track area. The fast track system appears to be an effective method by which an urban pediatric ED can efficiently maintain patient flow in light of limited resources, space constraints, limited manpower, and an increasing census.
Academic Medical Centers↗
Female genital mutilation: an overview.
The literature on female genital mutilation (also known as female circumcision) within a feminist theoretical context is discussed. Issues of culture, politics and religion in the literature will be examined in relation to feminist thought and the paper will also assess the effects of female genital mutilation on women's health and status within developing societies. Parallels with other similar practices in developed and developing countries will be drawn and policy strategies discussed.
Adolescent↗
Do gastric inhibitory polypeptide and glucagon-like peptide-1 (7-36) amide contribute to the hyperinsulinaemia of pregnancy?
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Adult↗
General practitioners' attitudes to variations in referral rates and how these could be managed.
BACKGROUND: Hospital referral rates have received widespread attention for both clinical and economic reasons. OBJECTIVE: This study was undertaken to find out the views of general practitioners in North Yorkshire on current arrangements for the feedback of routine referral data, perceived factors that influenced their referral behaviour and changes that might help their referral decisions. METHOD: Survey questions were chosen from the issues raised during semi-structured interviews with 11 selected practices. A postal questionnaire was sent to all 114 general practices in North Yorkshire. RESULTS: A 60% (68/114) response rate was obtained from the postal questionnaire. The majority of practices agreed that the referral information supplied by them was accurate (77%) and that the feedback of this data was useful (66%). Uncertainty of diagnosis/management and patient pressure were the two most commonly agreed factors that were suggested as influencing referral behaviour. Training in procedures and use of clinical guidelines were the most popular changes chosen as being helpful in referral decision making. CONCLUSIONS: The feedback of routine referral data is considered accurate and useful, and should continue. Expanding opportunities for the training of general practitioners in specific skills and the development of clinical guidelines for the management and referral of commonly suggested areas would be helpful to general practitioners in making referral decisions.
Decision Making↗
Perceptions of orthodontic treatment need: Receiver Operating Characteristic analysis.
This study aimed to investigate the variations in dentists' perception of need for orthodontic treatment. Sixteen dentists viewed forty clinical vignettes and recorded their decisions according to the certainty with which they would offer treatment for each case. Receiver Operating Characteristic (ROC) analysis was performed on this data, using the Index of Orthodontic Treatment Need (IOTN) as the "gold standard'. The data suggest that dentists treatment decisions do not concur with current guidelines in use in the UK.
Attitude of Health Personnel↗
Total UK multi-centre experience with a novel arterial occlusion device (Duct Occlud pfm).
OBJECTIVE: To report the total UK multicentre experience of a novel arterial occlusion device (Duct Occlud pfm). DESIGN: Descriptive study of selected non-randomised paediatric patients with a variety of aortopulmonary connections. SETTING: Five UK tertiary referral centres for congenital heart disease. PATIENTS AND METHODS: Between March 1994 and February 1995, 57 children aged 2 weeks to 14 years (median 50 months) underwent attempted closure of their aortopulmonary connection. Fifty one had persistent arterial ducts and 9 of them had had a Rashkind umbrella device implanted. Five patients had superfluous modified Blalock-Taussig shunts (mBTS). In one there was also a native major aortopulmonary collateral artery (MAPCA). Another patient had a native major aortopulmonary connection (APC). Transcatheter occlusion was attempted in all cases through a 4 F delivery catheter. RESULTS: Devices were successfully deployed in 49/57 (86%) patients. Seven of 51 cases with persistent arterial ducts were judged too large for the device and a Rashkind umbrella was used. 40 (91%) of the 44 in whom the detachable coil device was used had complete occlusion at 24 hours on colour flow Doppler echocardiography. Devices were successfully deployed in all 6 remaining patients (4 mBTS, 1 mBTS + MAPCA, and 1 APC). Embolisation of a device occurred on 4 occasions. Two devices were not retrieved but caused no apparent clinical problems. CONCLUSION: This novel detachable coil type occlusion system compares favourably with other methods of transcatheter occlusion of native, residual, or surgically created aortopulmonary shunts. The delivery system allows its use in small children.
Adolescent↗
Role of aerobic capacity and body mass index in the age-associated decline in heart rate variability.
The extent to which age-associated changes in aerobic capacity and body composition modulate the age-associated decline in heart rate variability (HRV) is unknown. We therefore measured HRV, peak O2 consumption (VO2peak) during treadmill testing, and relative weight (body mass index; BMI) in 164 healthy normotensive adults (75 men, age 20-87 yr) from the Baltimore Longitudinal Study on Aging. Two components of HRV, respiratory sinus arrhythmia (RSA; 0.12-0.40 Hz) and 0.10-Hz variability (0.06-0.10 Hz), were extracted from 8-min electrocardiogram recordings in the supine, seated, and standing postures. RSA, 0.10-Hz variability, and VO2peak varied inversely with age; BMI was unrelated to age. Age contributed 15.5-21.1% independent variance to RSA and 13.2-17.3% independent variance to 0.10-Hz HRV. VO2peak did not contribute significantly to RSA or 0.10-Hz HRV beyond the effect of age in any posture. There were no consistent independent contributions of BMI to HRV. Thus, in this population-based sample, age-associated changes in aerobic capacity and relative body weight do not provide the primary explanation for the decline in HRV observed with advancing age.
Adult↗
Orthostatic hypertension due to vascular adrenergic hypersensitivity.
Autoregulatory mechanisms ensure relatively small fluctuations of blood pressure with postural changes in healthy people. Although orthostatic hypotension is well recognized and commonly encountered, there are only a few reports of orthostatic hypertension. Most of the reported cases of orthostatic hypertension were related to excessive venous pooling, with an initial drop in cardiac output followed by overcompensation with an excessive release of catecholamines, or to nephroptosis with orthostatic activation of the renin-angiotensin system. We describe a 44-year-old woman with normal supine blood pressure and severe orthostatic hypertension who did not demonstrate an initial decrease in cardiac output and had normal plasma and urinary catecholamines and renin release. Pharmacological tests of autonomic nervous system function showed an increased pressor sensitivity to norepinephrine (11 to 14 times normal), normal sensitivity to isoproterenol, diminished baroreceptor reflex sensitivity, and exquisite sensitivity to alpha-adrenergic blockers. This unusual case of orthostatic hypertension appears to be secondary to vascular adrenergic hypersensitivity.
Adrenergic alpha-Antagonists↗
The entero-insular axis in polycystic ovarian syndrome.
We investigated the contributions made by the entero-insular axis, proinsulin and the fractional hepatic extraction of insulin to the hyperinsulinaemia characteristic of polycystic ovarian syndrome (PCOS). We measured plasma glucose, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (7-36 amide) (GLP-1(7-36) amide), immunoreactive insulin (IRI), intact proinsulin (IPI), and C-peptide concentrations during a 75 g oral glucose tolerance test in seven normal weight women with PCOS and eight healthy women. Women with PCOS had higher fasting (P = 0.05) and integrated (P < 0.01) IRI concentrations than controls. Fasting C-peptide levels were similar in both groups but integrated C-peptide (P < 0.05) concentrations were greater in PCOS subjects than controls. Fasting and integrated concentrations of glucose, GIP and GLP-1(7-36) amide were similar in subjects with PCOS and controls. Although fasting IPI concentrations were similar in both groups, integrated IPI concentrations were higher (P = 0.05) in patients with PCOS. Women with PCOS had similar fasting but higher (P < 0.05) integrated IRI:C-peptide molar ratios than controls. Fasting and integrated IPI:IRI molar ratios were similar in both groups. These results confirm that lean women with PCOS have peripheral hyperinsulinaemia. The mild fasting hyperinsulinaemia is due to increased pancreatic secretion, whereas the stimulated hyperinsulinaemia is due to both pancreatic hypersecretion and reduced fractional hepatic extraction of insulin. Hyperproinsulinaemia is modest and appropriate in PCOS, GIP and GLP-1(7-36) amide do not contribute to the stimulated hyperinsulinaemia in PCOS.
Adult↗
Factors influencing the uptake of orthodontic treatment.
The aim of this investigation was to evaluate the factors that influenced the uptake of orthodontic treatment for patients who were referred for orthodontic treatment to two types of orthodontic treatment provider; a fee per item and hospital service. The following data were collected: (i) basic demographic data; (ii) the need for orthodontic treatment as measured by IOTN; and (iii) the outcome of the consultation. The data analysis with logistic regression revealed that the following variables had a predictive effect on the uptake of treatment: (i) the need for orthodontic treatment; and (ii) the patient's gender. Most of the patients that were referred and accepted for treatment had a definite need for orthodontic treatment.
Adolescent↗
Hawaii medics find unified voice.
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Competitive Bidding↗
Demographic variation in the rate of knee replacement: a multi-year analysis.
OBJECTIVE: The aim of this study is to describe the practice variation of knee replacements (KRs) in the elderly ( > or = 65) over time from 1985-1990 in terms of the number of primary, bilateral, and revision KRs; the extent of large area variation in performance rates; and the degree to which demographic variables are the determinants of area rates. DATA SOURCES/STUDY SETTING: Data analyzed are from every hospital in the United States that performed a KR on a Medicare patient during the study period. Data were obtained from the MEDPAR, HISKEW, and denominator files of the Medicare Statistical System. STUDY DESIGN: This is a cohort study of all Medicare beneficiaries who received a KR between 1985 and 1990. The dependent variable in the analyses was the count of the KRs performed in each area. DATA COLLECTION/EXTRACTION METHODS: This is a population-based sample of Medicare enrollees in the United States. All hospitalizations for Medicare-reimbursed KRs were included in the initial data set. Exclusion criteria were used to identify the Medicare covered population with a definite KR. These criteria resulted in 7.3 percent exclusions and a final set of 414,079 KR hospitalizations. PRINCIPAL FINDINGS: The number of Medicare-funded KRs increased in each of the study years corresponding to an annual rate of increase of 18.45 percent. The likelihood of receiving a KR was a function of age, gender, and race. For each year, KRs were almost-twice as likely to be performed on women than on men. The odds of whites getting the surgery were over 1.5 times greater than for blacks. Even after adjusting for demographic factors, significant regional variation remained. CONCLUSIONS: Much about area variation and the rate of growth in KR rates remains unexplained. For answers to emerge, better data and different types of studies are required.
Age Factors↗