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Biomedical subjects

N Johnson

Publications and source records attributed to N Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1998

p53 alterations and HPV infections are common in oral SCC: p53 gene mutations correlate with the absence of HPV 16-E6 DNA.

To examine the association between HPV infections and p53 gene aberrations, a panel of 28 oral squamous cell carcinomas (SCC) and 12 potentially malignant oral mucosal lesions were analysed for p53 mutations in exons 2-9. p53 protein was analysed by immunocytochemistry using DO7 antibody. The same panel was also examined for the possible presence of HPV infection. p53 overexpression was detected in 13/26 (50%) malignant and 2/9 (22%) premalignant lesions. Mutations in the coding region of the p53 gene were found in 10 malignant samples. None of the premalignant lesions were shown to have p53 mutations. The total number of p53 mutations in 10 samples were 14 of which 12 (85%) were in exon 5 suggesting the presence of hot spots in exon 5 for carcinogens involved in the transformation of oral epithelial cells. The presence of HPV DNA was first screened with consensus primers to the L1 region and nested PCR approach. HPV 6 and HPV 16 were detected in 14/28 (50%) oral SCC and 4 of 12 (33%) precancerous lesions, 7 tumours harboured both types. The samples were then examined for the presence of E6 oncogenic sequence of HPV16 using E6 specific primers. 7/27 (26%) SCC and 5/9 (55%) premalignant lesions harboured E6 DNA of which 6 (3 SCC and 3 premalignant) were negative with L1 primers suggesting possible integration of the specific viral genes or loss of other viral DNA sequences after integration of larger viral fragments. 9/10 (90%) SCC with p53 mutations were negative for E6 DNA. Our results show that both p53 alterations and HPV infection may be important etiological factors in the development of oral cancer. However, there is: i) No concordance between p53 mutations and its overexpression. ii) the presence of HPV capsid DNA (L1) does not necessarily indicate the presence of HPV oncogenic genes. iii) p53 gene mutations, but not overexpression, correlate with the absence of HPV 16-E6 and not L1 gene.

Aged↗
PubMed1998

The career outcomes for doctors completing general practice vocational training 1990-1995.

BACKGROUND: While much has been published about the career outcomes of doctors who completed general practice vocational training prior to 1990, no evidence is currently available about those who have qualified since that time. AIM: To obtain information about the career paths of doctors who had completed general practice vocational training since 1990, and to compare the results with previously published data. METHOD: Postal questionnaire survey of all doctors completing vocational training during the period 1990-1995 in three regions of the United Kingdom. The study examined current work status, career path since completion of training, desire for and experience of part-time training, degree of difficulty in choosing and following a career, and the degree to which certain factors impeded career choice. RESULTS: The overall response rate was 64.8%, although there was a significant difference between the response rates for men and women. While virtually all responders were employed, with the majority working in general practice, women were significantly less likely than men to be working as principals in general practice, for all cohorts. These results were very similar to those cohorts described in earlier studies. The career paths of doctors only became stable after about four years. Of those working in general practice, about 20% found it difficult to choose their career, and about 10% found it difficult to follow their career. Out-of-hours work was the major factor impeding career choice. CONCLUSION: Although they are taking longer to reach, the final career destinations of doctors completing vocational training since 1990 are no different from those of earlier cohorts.

Career Choice↗
PubMed1998

The current state of bone and tissue banking in Australia.

The development of bone and tissue banking in Australia over the last decade is described and details of the administrative structure, donor and recipient testing protocols, allograft segment processing procedures, and internal audit safety arrangements are also provided. Demographic data concerning both the retrieval and dispersal of musculoskeletal allograft materials in Australia are also discussed. Current price schedules for a variety of allograft materials available in Australia are made available for international comparison.

Australia↗
PubMed1998

Metabolism of 3H/14C-labeled 4''-deoxy-4''-epimethylaminoavermectin B1a benzoate in chickens. Identification of novel fatty acid conjugates of '4'-deoxy-4''-epimethylaminoavermectin B1a.

The metabolism of 3H/14C-labeled 4"-deoxy-4"-epimethylaminoavermectin B1a (MAB1a) benzoate, the major homologue (>/=90%) of the avermectin insecticide emamectin benzoate, was studied in laying chickens. Ten Leghorn hens (Gallus domesticus) were orally dosed once daily for 7 days (1 mg/kg of body weight/day). Eggs and excreta were collected daily, and eggs were subsequently separated into whites and yolks. Chickens were euthanized within 20 hr after the last dose, and liver, kidney, heart, muscle, fat, ovaries, gizzard, gastrointestinal tract and contents, and carcass were collected. Approximately 70 and 6% of the total administered dose were recovered in the excreta plus gastrointestinal tract and contents and in the tissues plus eggs, respectively. Two novel metabolites, i.e. the 24-hydroxymethyl derivative of the parent compound (24-hydroxymethyl-4"-deoxy-4"-epimethylaminoavermectin B1a) and the N-demethylated derivative of 24-hydroxymethyl-4"-deoxy-4"-epimethylaminoavermectin B1a (24-hydroxymethyl-4"-deoxy-4"-epiaminoavermectin B1a), were identified. In addition, eight fatty acid conjugates of each of these two metabolites, comprising 8-75% of total radioactive residues in tissues and eggs, were isolated and identified. Although this represents some of the most extensive in vivo fatty acid conjugation to a xenobiotic reported to date, potential human exposure to MAB1a residues from consumption of chicken would be extremely low, because the dosage level in this study was approximately 1000-fold greater than the MAB1a residue levels seen in crops and because the majority of the applied dose was recovered in the excreta. Based on these findings, the avian biotransformation of MAB1a differs substantially from the mammalian biotransformation.

Animals↗
PubMed1998

Action STAT! The crisis nurse.

To provide quality care with limited staff and create a safer environment, managers created a new "crisis nurse" position.

Emergency Service, Hospital↗
PubMed1997

Dysregulation of the interleukin-2 receptor alpha- and beta-chain expression in CD4 and CD8 T cells in HIV infection.

Peripheral blood mononuclear cells were prepared from human immunodeficiency virus-positive (HIV+) individuals (n = 46) to investigate the expression of both chains of the interleukin-2 receptor. Both qualitative and quantitative changes in expression were observed. Total lymphocyte expression of the IL-2 alpha chain (CD25) was decreased compared with HIV-negative (HIV-) controls. This was due to the decrease in the CD4+ population, which favored expression of this receptor, rather than a decrease in expression, per se. CD8+ lymphocytes expressed the beta chain (CD122) in the absence of the alpha chain. However, a significant increase in the number of peripheral blood CD8+ lymphocytes expressing mainly the beta subunit was observed in HIV+ patients (P = 0.02). This was observed to a similar extent in asymptomatic and symptomatic patients and characterized a subpopulation of T lymphocytes expressing high levels of CD8. Lymphocytes from patients with advanced HIV disease failed to up-regulate both alpha and beta chains in response to mitogenic concentrations of phytohaemagglutanin. However, those cells that were able to up-regulate both of the IL-2 receptors were capable of effective signal transduction through the receptor, increasing the proliferative response to stimulation.

CD4-Positive T-Lymphocytes↗
PubMed1997

Construction of an epitope vector utilising the diphtheria toxin B-subunit.

An immunogenic loop within the diphtheria toxin has been deleted from the B-subunit by a modification of the inverse polymerase chain reaction (IPCR) and replaced by a unique restriction endonuclease site. An oligonucleotide encoding an identified epitope sequence from the major outer membrane protein of Neisseria meningitidis of similar size and structure to that deleted has been introduced into the restriction site. Expression of the resulting chimeric B-subunit from Escherichia coli yielded a protein that was recognised by a panel of antibodies specific for the meningococcal epitope. Initial immunisation data suggest that this protein could elicit an antibody response against both diphtheria toxin and meningococcal proteins.

Animals↗
PubMed1997

Camptothecin causes cell cycle perturbations within T-lymphoblastoid cells followed by dose dependent induction of apoptosis.

We have investigated the effect of the anticancer compound, camptothecin on Jurkat T-cells, a lymphoblastoid leukemic cell-line. Exposure to low concentrations led to rapid cessation of DNA (more than 95%) and RNA (more than 75%) synthesis. Perturbations to the cell cycle were observed following exposure which caused a significant accumulation of cells within G1 (P = 0.03) with a concomitant decrease in G2/M (P = 0.025). Concentrations below 0.1 microM could inhibit DNA synthesis but not induce apoptosis. Induction of apoptosis was dose dependent and could be detected as early as 3 h post exposure. The apoptotic population appeared to be derived from G1 and S-phase cells but not G2/M, coinciding with the cell cycle compartments in which DNA and RNA polymerases function. However, direct inhibition of DNA polymerase alone was not shown to be associated the induction of apoptosis or with a decrease in susceptibility to camptothecin-induced cell death. The effects of camptothecin on Jurkat T-cells and the potential mechanisms involved are discussed in the context of observations made in other transformed cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed1997

A randomised trial evaluating pain and bleeding after a first trimester miscarriage treated surgically or medically.

Miscarriage treated surgically and medically were compared in a randomised controlled trial evaluating pain and bleeding. Surgery is associated with less pain (P < 0.03) and vaginal bleeding (duration and severity, P = 0.001) than medical treatment, fewer daily hospital attendances (2.5 compared with three, P = 0.04) but a greater drop in haemoglobin concentration (difference, 1 g/dl; CI95% = 0.3-1.6).

Abortion, Spontaneous↗
PubMed1997

Mortality effects of community socioeconomic status.

We linked data from the National Longitudinal Mortality Study to census tract information on 239,187 persons to assess 11-year mortality risk among black and white women and women associated with median census tract income, adjusted for individual family income from the Current Population Survey. We stratified Cox proportional hazards models by ages 25-64 years and 65 years and older. We used a robust covariance matrix to obtain standard errors for the model coefficients that account for correlation among individuals in the same census tract. Both income indicators were independently related to all-cause mortality. Among persons age 25-64 years, the rate ratios (RR) for individual family income and the median census tract income, respectively, for low income relative to high income were RR = 2.10 vs. 1.49 for black men, RR = 2.03 vs 1.26 for white men; and RR = 1.92 vs 1.30 for black women and RR = 1.61 vs 1.16 for white women. Among persons age 65 years or greater, only individual family income was associated with mortality, and only for white men. Although family income has a stronger association with mortality than census tract, our results indicate that, more broadly, area socioeconomic status makes a unique and substantial contribution to mortality and should be explored in health policy and disease prevention research.

Adult↗
PubMed1997

Pancreatic trauma in children: mechanisms of injury.

BACKGROUND: Pancreatic trauma occurs in up to 10% of all cases of blunt pediatric trauma. Here we attempted to identify markers of pancreatic injury in children and to assess our current diagnostic approach to pancreatic injury. METHOD: We performed a retrospective chart review of all patients with a pancreatic injury admitted to a Level I pediatric trauma center between January of 1980 and September of 1994. RESULTS: In all, 26 children were included. All pancreatic injuries were due to blunt trauma. Handlebar injuries were the most common mechanism of injury and resulted in a unique pattern of isolated pancreatic trauma, often complicated by the development of a pseudocyst. Computed tomographic scans, performed with intravenous and oral contrast and done in the acute setting, were 85% sensitive for diagnosing a pancreatic injury. CONCLUSIONS: Double contrast computed tomographic scan is a more sensitive test than ultrasound in diagnosing pancreatic injury. The constellation of abdominal pain, an elevated serum amylase and a handlebar mechanism of injury warrants hospitalization and a double contrast abdominal computed tomographic scan.

Adolescent↗
PubMed1997

Content validity of a trainer's report: summative assessment in general practice.

A structured trainer's report for use in summative assessment in general practice has been designed, and it is important that the content validity of this report is tested before it is widely adopted. The aim of this paper was to assess the content validity of a proposed report from the perspective of doctors who have recently completed vocational training. A postal questionnaire survey was sent out seeking the views of 220 doctors who had completed vocational training in 1994 as to whether or not the proposed contents were items that are needed in general practice, and whether or not the items were suitable for assessment by means of a trainer's report. The response rate was 73.3%. More than 85% of respondents agreed that the 31 items proposed for inclusion in the trainer's report were needed in general practice. While the proportions agreeing that the items were suitable for assessment by a trainer's report were considerably lower, for 26 items significantly more agreed that they were suitable than disagreed. Analysis of the freetext comments made by respondents illustrated their concerns. The results provide support for the content validity of this proposed trainer's report; however it is important that the concerns expressed are addressed.

Adult↗
PubMed1997

Randomised trial comparing a policy of early with selective amniotomy in uncomplicated labour at term.

OBJECTIVE: To compare two management policies: rupture of the fetal membranes when women are in normal labour or leave them intact as long as feasible. SETTING: The labour ward of a city university hospital. DESIGN: Automated randomised clinical trial. PARTICIPANTS: 1540 women in uncomplicated term labour. Data on labour duration, blood loss, oxytocin use and fetal condition were collected from 1132 women. Some data from nulliparous women has been presented earlier by the UK Amniotomy Group. MAIN OUTCOME MEASURES: Duration of labour, Apgar score, fetal morbidity and maternal morbidity including perineal injury, mode of delivery, epidural rates and the total number of vaginal examinations in the first stage of labour after amniotomy. INTERVENTIONS: Amniotomy at the next vaginal examination or amniotomy only if indicated. The median cervical dilatation at membrane rupture was 2 cm greater in the first group. RESULTS: A policy of routine amniotomy in labour had no measurable advantage over selective amniotomy for parous women (difference = 4 min) but shortened labour in nulliparous women by 1 h (Mann-Whitney U test: P < 0.05). There was a suggestion of a higher caesarean section rate (OR 1.9; 95% CI 0.9-3.5), and there were more vaginal examinations after membrane rupture in the group allocated routine amniotomy. There were no measurable differences in oxytocin use, fetal condition at birth, retained placenta rates, blood loss, pain or analgesia requirements. CONCLUSION: Routine amniotomy may shorten the first labour but not subsequent ones. There is a suggestion that routine surgical interference may be harmful by increasing the risk of caesarean section, and this agrees with data from other trials (common odds ratio 1.2; 95% CI 0.92-1.6).

Adult↗
PubMed1997

Randomised controlled trial of cardiotocography versus umbilical artery Doppler in the management of small for gestational age fetuses.

OBJECTIVE: To compare the impact on use of resources in the management of small for gestational age babies using Doppler ultrasound versus cardiotocography. DESIGN: A randomised controlled trial. SETTING: A large district general hospital delivering 5500 to 6000 infants each year, 30% to 35% of which are to women of Pakistani origin. POPULATION: One hundred and fifty women delivered of small for gestational age infants. MAIN OUTCOME MEASURES: Primary outcome measures were length of hospital inpatient stay and induction of labour rates. Secondary outcome measures included caesarean section rates and length of stay on neonatal unit. RESULTS: The use of Doppler reduced average hospital inpatient stay from 2.5 days to 1.1 days, compared with cardiotocography (P = 0.036). There was no effect on induction of labour rates or caesarean section rates. There was no significant difference in length of stay on the neonatal unit (P = 0.33). There was a reduction in monitoring frequency and fewer hospital antenatal clinic visits. CONCLUSION: The use of Doppler ultrasound to manage small for gestational age infants reduces the use of resources, compared with cardiotocography.

Cardiotocography↗
PubMed1997

Alzheimer's disease in the United Kingdom: developing patient and carer support strategies to encourage care in the community.

Alzheimer's disease is a growing challenge for care providers and purchasers. With the shift away from the provision of long term institutional care in most developed countries, there is a growing tendency for patients with Alzheimer's disease to be cared for at home. In the United Kingdom, this change of direction contrasts with the policies of the 1980s and 90s which focused more attention on controlling costs than on assessment of the needs of the patient and carer and patient management. In recent years, the resources available for management of Alzheimer's disease have focused on institutional care, coupled with drug treatment to control difficult behaviour as the disease progresses. For these reasons, the current system has led to crisis management rather than preventive support--that is, long term care for a few rather than assistance in the home before the crises occur and institutional care is needed. Despite recent innovations in the care of patients with Alzheimer's disease, the nature of the support that patients and carers receive is poorly defined and sometimes inadequate. As a result of the shift towards care in the community, the informal carer occupies an increasingly central role in the care of these patients and the issue of how the best quality of care may be defined and delivered is an issue which is now ripe for review. The objective of this paper is to redefine the type of support that patients and carers should receive so that the disease can be managed more effectively in the community. The needs of patients with Alzheimer's disease and their carers are many and this should be taken into account in defining the quality and structure of healthcare support. This paper shows how new initiatives, combined with recently available symptomatic drug treatment, can allow patients with Alzheimer's disease to be maintained at home for longer. This will have the dual impact of raising the quality of care for patients and improving the quality of life for their carers. Moreover, maintaining patients in a home environment will tend to limit public and private expenditure on institutional care due to a possible delay in the need for it.

Aged↗