The importance of obtaining ethical approval.
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Biomedical subjects
Publications and source records attributed to J Hunt.
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The clinical significance of GB virus C (GBV-C E2) antibody is under investigation. The prevalence rates of GBV-C RNA and antibody to GBV-C E2 glycoprotein were determined in a population of 123 Egyptian anti-hepatitis C virus (HCV)-positive patients with chronic liver disease (CLD) who had not been treated previously with interferon. Sera were tested for GBV-C RNA by the LCx assay (Abbott Laboratories, North Chicago, IL), and for GBV-C E2 antibody by enzyme immunoassay. GBV-C RNA was present in 11.4% of patients. GBV-C E2 antibody was detected in 55.9% of GBV-C RNA-negative patients and in 2.2% of GBV-C RNA-positive patients (P = 0.006). GBV-C RNA was associated significantly with a history of schistosomiasis (relative risk [RR] = 5.83, 95% confidence interval [CI] 1.99-17.14, P < 0.005) but not with parenteral risk factors. The presence of GBV-C E2 antibody was not associated with age, gender, parenteral risk factors, schistosomal infection, or HCV viremia. The HCV genotype and level of viremia were similar in GBV-C anti-E2-positive and negative patients. There was a trend toward more severe histological disease with anti-E2 seropositivity (RR = 1.45, 95% CI 0.89-2.45, P = 0.11), an association which was independent of the evidence of schistosomiasis. It is concluded that GBV-C infection is common among HCV-infected Egyptian patients with CLD due to HCV infection. A significant negative correlation between the GBV-C viremia and GBV-C E2 antibody suggests that an antibody response is associated with viral clearance. This antibody response presumably occurs spontaneously, as none of the patients had received antiviral therapy. The unexpected association between GBV-C RNA and schistosomiasis suggests that nonparenteral or occult parenteral routes of GBV-C infection are likely to be important.
Counselling in reproductive medicine has tended to focus on bereavement theory as the primary model of understanding and practice. This has meant that the experience of infertility has principally been conceptualized as a process with definable stages, leading smoothly, in time, to resolution and acceptance. This paper suggests that, whilst this is a valuable theory of the psychological and emotional components of infertility, it is also important to consider depression as a particularly significant aspect, independent of its being seen as a stage in the mourning process. The paper outlines an understanding of depression and gives case illustrations of the significance of depression for some people with infertility problems. The evidence for the prevalence of depression amongst those with impaired fertility and the various areas of personal functioning which might be affected are considered. Cognitive therapy has come to be widely accepted as an important approach to treating depression. The theoretical and research evidence for the efficacy of cognitive therapy is discussed, and how it might be applied in the context of infertility counselling.
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Life-threatening disease can trigger positive effects such as greater appreciation for life and enhanced interpersonal relationships. Little research has examined these salutary effects or their association with quality of life (QOL). Adult bone marrow transplantation (BMT) survivors (n = 90) were interviewed regarding psychosocial sequelae of BMT and completed indices of QOL and psychological adjustment. Thematic analysis was used to code interview responses into discrete categories of negative and positive sequelae. Multiple regression analyses indicated POSTOTAL scores were inversely associated with time post-BMT and positively associated with negative prognostic factors at BMT. Scores on indices of QOL and psychological adjustment were significantly correlated with reports of negative post-BMT sequelae but unrelated to positive sequelae. It was concluded that life-threatening disease can trigger positive sequelae that can contribute to QOL. However, standard QOL indices may not measure this positive QOL dimension, thus yielding a potentially incomplete picture of current QOL.
The free TRAM flap is now commonly used in breast reconstruction after mastectomy. A number of our patients reported anecdotally return of some sensation in their reconstructed breasts, despite being told beforehand that this was unlikely. This study measured return of sensation in a series of 21 patients, by studying both patients' subjective reporting of sensory return using a standardised questionnaire and objective evaluation of sensation with standard clinical tests. These included temperature and pain threshold and the use of the Semmes-Weinstein method. The study demonstrates that measurable sensory recovery occurred in 16 of our 21 patients (76%). 18 of the 21 patients (86%) reported a subjective feeling of sensation in the reconstructed breast and 7 (33%) claimed it felt the same as their normal contralateral breast. Sensory recovery usually commences about 6 months postoperatively and progressively improves over time. These findings demonstrate that the free tissue transfer method does not necessarily lead to an insensate reconstruction, as might be supposed.
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UNLABELLED: The Glasgow Coma Scale (GCS) has been shown to be a valuable tool in assessing the neurologic and physiologic status of critically ill patients. Unfortunately, the GCS requires assessment of the verbal response of the patient and this can be blocked by intubation. The purpose of this study was to assess the ability of a regression model based upon the eye and motor components of the GCS to accurately predict the verbal response of the GCS. The primary hypothesis was that the verbal response could be derived from the motor and eye responses of the GCS. METHODS: Data were collected prospectively in an intensive care unit computer data base. Patients were divided into training and test data sets. Linear regression was used to derive a model of verbal score from the motor and eye scores of the GCS in the training data set. Correlation between the actual and the predicted verbal scores was calculated. RESULTS: A total of 2,521 GCS assessments were available for analysis. The second order multiple regression model was an accurate predictor of the verbal score (Pearson's Correlation r = 0.9, R2 = 0.8, p = 0.0001) in 1,463 observations in the training data set. Second Order Multiple Regression Model: Estimated GCS Verbal = (2.3976) + [GCS Motor x (-0.9253)] + [GCS Eye x (-0.9214)] + [(GCS Motor)2 x (0.2208)] + [(GCS Eye)2 x (0.2318)] where r = 0.91, R2 = 0.83, and p = 0.0001. The accuracy of this model was confirmed by comparing the predicted verbal score to the actual verbal score in the test data set (n = 736, r = 0.92, R2 = 0.85, p = 0.0001) CONCLUSIONS: The GCS is a useful tool in the intensive care unit and a critical part of the APACHE II assessment of patient acuity. GCS has been shown to be a useful tool in its own right as a predictor of outcome in the critically ill. Its use is limited with intubation. (See Segatore M, Way C: Heart Lung 21:548, 1992; and Lieh-Lai MW, Theodorou AA, Sarnaik AP, et al: J Pediatr 120:195, 1992.) The present study demonstrates that a relatively simple regression model can use the eye and motor components of the GCS to predict the expected verbal component of the GCS, thus allowing the calculation of the GCS sum score in intubated patients.
The pro-inflammatory cytokine tumor necrosis factor (TNF) is dramatically and transiently elevated in the circulation during endotoxic and septic shock and is a primary mediator in the pathogenesis of the sepsis syndrome. TNF peaks in the circulation 90 min after endotoxin administration with little variation, even among species. The specific cells, tissues, or organs that produce the high circulating level of TNF in septic shock remain unknown. The most likely sources are macrophage-laden tissues such as the liver and the spleen and circulating blood leukocytes. This study evaluated whether the liver is an important source producing the TNF spike 90 min after endotoxin. To test this hypothesis, we measured the peak circulating level of TNF following an endotoxin injection in rats subjected to a two-thirds hepatectomy versus sham-operated controls. Hepatechectomized rats produced 64% less TNF after endotoxin than controls (857 + or - 143 pg/mL plasma vs. 2410 + or - 491, respectively; p < .01). In contrast, splenectomy did not significantly after peak TNF levels versus sham-operated controls following an endotoxin injection (1380 + or - 148 pg/mL plasma vs. 1710 + or - 291). Furthermore, incubation of rat blood with endotoxin for 90 min did not significantly increase TNF above controls. These experiments demonstrate an important role for the liver in producing the high circulating levels of TNF after an endotoxin injection and suggest that hepatic-specific cytokine modulation deserves study for a therapeutic benefit in septic shock.
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AIM: To assess overexpression of the proposed tumour suppressor gene product p53 using the mouse monoclonal antibody DO-7 in the three main subtypes of carcinoma of the uterine cervix and to evaluate its value as a prognostic indicator. METHODS: Eighty two cases of FIGO Stage IB/IIA uterine cervical carcinoma were studied retrospectively. The tumours had been previously typed into adenocarcinomas, squamous carcinomas and adenosquamous carcinomas after the tissue had been fixed in formalin and embedded in paraffin wax. p53 protein expression was assessed using a standard immunohistochemical technique and the findings were correlated with tumour type, lymph node status and clinical outcome. RESULTS: In total, the p53 gene product was overexpressed in 17.1% (14/82) of all carcinomas and also in areas of cervical intraepithelial neoplasia grade III adjacent to invasive squamous carcinoma. Where present, the normal epithelium was uniformly negative. No association was found between p53 overexpression and tumour subtype, lymph node status or clinical outcome. CONCLUSIONS: It seems unlikely that p53 analysis will be of value in determining prognosis in carcinoma of the uterine cervix.
Lymphatics serve to remove from the interstitium a range of materials, including plasma proteins, colloid materials, and cells. Lymph flow rates can be enhanced by periodic tissue compression or venous pressure elevation, but little is known to what degree enhancement of lymph flow affects material transport. The objective was to examine the uptake of plasma proteins, a colloidal perflubron emulsion (LA-11063, mean particle diameter = 0.34 micron), and leukocytes into lymphatics. Prenodal collecting lymphatics in the lower hindlimb of rabbits were cannulated with and without foot massage and after elevation of venous pressure (40 mmHg). The average lymph flow rates were elevated approximately 22-fold by the skin massage but only about threefold by venous pressure elevation. Lymph-to-plasma protein concentration ratio remained unchanged by the massage but decreased significantly after venous pressure elevation. Lymph colloid concentration and leukocyte counts were elevated on average 47 and 8.5 times, respectively, by foot massage, but both decreased after venous pressure elevation. These results suggest that skin movement by massage and elevation of the venous pressure lead to opposite lymph transport kinetics of protein, colloids, and cells. Massage is more effective to enhance material transport out of the interstitium into the initial lymphatics.
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BACKGROUND: The organization and management of general practice is changing as a result of government policies designed to expand primary health care services. One aspect of practice management which has been underresearched concerns staffing: the recruitment, retention, management and motivation of practice managers. AIM: A study set out to find out who is routinely involved in making decisions about staffing matters in general practice, to establish the extent to which the human resource management function is formalized and specialized, and to describe the characteristics of the practice managers. METHOD: A postal questionnaire was sent to a stratified random sample of 750 general practices in England and Wales in February 1994 enquiring about the practice (for example, the fundholding status and number of general practitioner partners), how the practice dealt with a range of staffing matters and about the practice manager (for example, employment background and training in human resource management). Practices were classed as small (single-handed and two or three general practitioner partners), medium (four or five partners) or large (six or more partners). RESULTS: Replies were received from 477 practices (64%). Practice managers had limited authority to make decisions alone in the majority of practices although there was a greater likelihood of them taking independent action as the size of practice increased. Formality in handling staffing matters (as measured by the existence and use of written policies and procedures) also increased with practice size. Larger practices were more likely than smaller practices to have additional tiers in their management structure through the creation of posts with the titles assistant practice manager, fund manager and senior receptionist. Most practice managers had been recruited from within general practice but larger practices were more likely than smaller practices to recruit from outwith general practice. Three quarters of practice managers reported having received some type of formal training in staff management. CONCLUSION: This study shows that practice size is a major factor associated with differences in the organization and management of staffing. Any initiatives which increase the scale of primary care functions and services would have to address the issues of communication and coordination that might be associated with such a change.
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Few names crop up so often in the context of water fluoridation as that of John Yiamouyiannis, an American who has campaigned hard to stop this public health measure not only in the United States but in other countries such as Britain. During 1993, Yiamouyiannis was given considerable air time by the BBC, appearing on its prestigious You and yours and Nature programmes where he denigrated the efforts of local health authorities to reduce tooth decay by means of fluoridating their water supplies. His dramatic claims about fluoridation--in particular, that it increases people's risk of dying of cancer--must understandably alarm those who take them at face value. So just who is John Yiamouyiannis? And do his allegations hold up? This review of his career is based on publicly documented records and statements.
We describe a cDNA from Chinese hamster ovary cells which encodes a protein 91 and 96% identical to bovine and rat mitochondrial rhodaneses, respectively. Recombinant protein was expressed from the cDNA in Escherichia coli, purified to homogeneity, and found to have kinetic properties nearly indistinguishable from those of the bovine enzyme, the only cloned rhodanese previously verified by characterization of the recombinant protein. The carboxyl-terminus of the enzyme is characterized by a duplicated tripeptide, which can be proteolytically processed in vivo. We constructed a mutant in which the last 5 amino acids were replaced by 28 residues of unrelated sequence. This protein was expressed, purified, and found to have kinetic constants similar to those of the wild-type enzyme. The functionally verified Chinese hamster rhodanese cDNA encodes a protein of 297 residues and differs from the rat enzyme at 13 positions. None of these substitutions occurs at residues suggested to play essential roles in catalysis or structural stabilization.