Virus-specific mechanisms of carcinogenesis in hepatitis C virus associated liver cancer.

The development of hepatocellular carcinoma (HCC) in persons who are persistently infected with hepatitis C virus (HCV) is a growing problem worldwide. Current antiviral therapies are not effective in many patients with chronic hepatitis C, and a greater understanding of the factors leading to progression of HCC will be necessary to design novel approaches to prevention of HCV-associated HCC. The lack of a small animal model of chronic HCV infection has hampered understanding of these factors. As HCV is an RNA virus with little potential for integration of its genetic material into the host genome, the mechanisms underlying HCV promotion of cancer are likely to differ from other models of viral carcinogenesis. In patients persistently infected with HCV, chronic inflammation resulting from immune responses against infected hepatocytes is associated with progressive fibrosis and cirrhosis. Cirrhosis is an important risk factor for HCC independent of HCV infection, and a majority of HCV-associated HCC arises in the setting of cirrhosis. However, a significant minority arises in the absence of cirrhosis, indicating that cirrhosis is not a prerequisite for cancer. Other lines of evidence suggest that direct, virus-specific mechanisms may be involved. Transgenic mice expressing HCV proteins develop cancer in the absence of inflammation or immune recognition of the transgene. In vitro studies have revealed multiple interactions of HCV-encoded proteins with cell cycle regulators and tumor suppressor proteins, raising the possibility that HCV can disrupt control of cellular proliferation, or impair the cell's response to DNA damage. A combination of virus-specific, host genetic, environmental and immune-related factors are likely to determine the progression to HCC in patients who are chronically infected with HCV. Here, we summarize current knowledge of the virus-specific mechanisms that may contribute to HCV-associated HCC.

Influence of patient posture on oxygen saturation during fibre-optic bronchoscopy.

This study was designed to investigate the effect of posture on oxygen saturation during fibre-optic bronchoscopy (FOB). Thirty-eight consecutive patients requiring diagnostic FOB were randomized into two groups according to the initial posture in which the FOB was performed. In group 1 (20 patients), FOB was commenced supine, and in group 2 (18 patients) in a semi-recumbent position (45 degrees from horizontal). Sedation with midazolam was titrated according to clinical response. All patients received atropine 0.6 mg intravenously and topical lignocaine. Observations of peak, trough and plateau oxygen saturation and pulse rate were recorded during six study periods, each lasting 3 min. Periods 1 and 2 were pre- and post-sedation without supplemental oxygen, respectively. The bronchoscope was then inserted into the distal end of the trachea and observations taken during periods 3 and 4 (no supplemental oxygen) and periods 5 and 6 (2 l oxygen by nasal cannulae). In group 1, posture was changed from supine to semi-recumbent from periods 3-4 and reversed in periods 5 and 6. In group 2, posture changes were in reverse sequence. Patients with initial oxygen saturation of less than 90% or showing a fall below 85% during FOB were excluded. Five patients from each group were withdrawn because of hypoxia. In both groups, oxygen saturation fell significantly (P<0.001) following sedation. There was no significant change in saturation (peak, trough or plateau) with change in posture from supine to semi-recumbency (group 1) or the reverse (group 2). These correspond to periods 3-4 and 5 6 in both groups. Supplemental oxygen was associated with a significant rise in oxygen saturation in both postures, attaining levels close to presedation levels.

Engaging staff nurses in evidence-based research to identify nursing practice problems and solutions.

This article illustrates how one academic health science center in a large metropolitan area sought to improve the quality of patient care by soliciting the input of their nursing staff in devising an action plan for change. The research model incorporated both survey and focus group methods used by nursing leaders in administration and practice to identify and prioritize nursing research and clinical needs in their organization. The goal was to establish consensus among clinicians and researchers about significant issues in the institution requiring in-depth attention. A second objective was to design a survey instrument that is easy to complete and could be distributed, collected, and analyzed easily, thereby providing empirical data to the clinicians in a timely manner and in a simple format. This expedited process enabled specific action plans to be developed around the identified problems. Moreover, the process promoted interest in advancing nursing research and evidence-based practice among the clinicians and administrators.

How long should Atrovent be given in acute asthma?

BACKGROUND: In acute asthma the optimal duration of treatment with combination beta agonist and anticholinergic nebuliser solutions is unknown; most studies have investigated single doses or treatment for up to 12 hours. To determine whether longer treatment with ipratropium bromide might aid recovery a study was undertaken in 106 patients with acute asthma. METHODS: A double blind, randomised, placebo controlled, three group study was performed with all patients receiving ipratropium for 12 hours and salbutamol for 60 hours after admission (both nebulised four hourly), systemic steroids and, if necessary, theophylline. At 12 hours ipratropium was stopped in group I (n = 35) but was continued in the other two groups, and at 36 hours ipratropium was also stopped in group II (n = 35) while patients in group III (n = 36) continued with ipratropium for 60 hours. Spirometric tests were performed before and after salbutamol, and again 30 and 60 minutes after ipratropium or placebo at 12, 36 and 60 hours. Peak flow rates (PEFR) were measured before and after each nebulisation. RESULTS: There were no differences between the groups in PEFR on admission (group I: 214 l/min, group II: 198 l/min, group III: 221 l/min), or mean forced expiratory volume in one second (FEV1) at 12 hours (group I: 1.81, group II: 2.01, group III: 2.21), 36 hours (group I: 2.11, group II: 2.31, group III: 2.41), or at 60 hours (group I: 2.21, group II: 2.31, group III 2.51). Despite this, median time to discharge was significantly higher for patients in group I (5.4 days) than for those in groups II (4.1 days) and III (4.0 days). CONCLUSIONS: Combination nebulised therapy can be continued beyond 12 hours and up to 36 hours after admission with improved recovery time. Lung function testing may not reflect the full benefit of treatment.

Diagnostic imaging of post-irradiation changes in the chest.

Thirty-nine patients were studied with regard to post-irradiation changes in the chest. Twenty of these were reviewed retrospectively and 19 studied prospectively. All patients had chest radiographs and computed tomography (CT) of the chest following radiotherapy. Nineteen also had ventilation and perfusion studies of the lung, including single photon emission computed tomography (SPECT) and these were correlated with the chest radiographs and computed tomography. The majority showed abnormalities on computed tomography, the commonest being areas of lung opacification and evidence of volume loss. Several patients also showed a reduction in the size of pulmonary vessels. In most but not all, the changes were also seen on the chest radiographs. Abnormalities were not confined to the radiation fields, the vascular changes being present in large areas of lung which had not been directly irradiated. The structural and functional abnormalities correlated well as shown by ventilation and perfusion scintigraphy. However, single photon emission computed tomography was more sensitive than planar scintigraphy in showing perfusion defects, and it also showed some defects in areas of lung which appeared normal on computed tomography and the chest film. Computed and photon emission tomography were considerably more sensitive than chest radiography in showing the changes due to irradiation. The chest radiograph is clearly an insensitive indicator of post-irradiation change in the lung. Functional abnormalities are more profound and extensive than the chest film suggests, even when it is positive. There are clear implications for the planning of radiotherapy fields affecting the chest in patients who have good prospects of long-term survival. The maximum damage is related to irradiation of the hilum or mediastinum and this should be avoided wherever possible.

Factors influencing mortality from infective endocarditis in two district general hospitals.

Factors influencing mortality were studied in 92 consecutive cases of infective endocarditis admitted to two district general hospitals between January 1975 and April 1982. Thirty two patients died, an overall mortality of 35%, 13 patients died before diagnosis and 19 despite aggressive antimicrobial therapy. Bactericidal antibiotic levels were monitored in 39 cases but these did not appear to influence outcome. Mortality was lowest for Streptococcus viridans infection (15%) but rose to 50% for infections with S. faecalis and other less common organisms. Most deaths were in patients over 50. Cardiac failure on admission was a poor predictor of mortality, although this was the principal cause of death during treatment (14 cases). Eight patients had emergency valve replacement and 3 died post-operatively. When the diagnosis was missed during life (13 cases) arterial embolus was a common presenting feature (46%). Classical signs of endocarditis, other than pyrexia, were absent. A cardiac murmur (always mitral incompetence) was noted in only 6 cases and considered to be insignificant.

Maintenance chemotherapy for anaplastic small cell carcinoma of the bronchus: a randomised, controlled trial.

Since March 1980, 309 patients with anaplastic small cell carcinoma of the bronchus (ASCB) have received remission induction therapy prior to randomisation to maintenance (M) or no maintenance (NM) chemotherapy. Induction therapy consisted of six courses of vincristine, doxorubicin and cyclophosphamide (VAC) given IV every 3 weeks. Those with limited disease also received mediastinal irradiation. Consenting patients with no unequivocal residual disease were randomised to have no further treatment until relapse or a further eight courses of VAC, at a lower dosage, every 4 weeks. Patients failing to achieve randomisation status received palliative treatment only. The median survival for all patients with limited disease (LD) is 363 days and that for patients with extensive disease (ED) is 272 days (P less than 0.00001). Sixty-one patients with ED were randomised. Those having maintenance chemotherapy lived significantly longer (median 372 days) than those who did not continue therapy (median 259 days) (P = 0.006). An imbalance in the proportion of 'complete remitters' randomised to maintenance therapy does not account for this difference. There is no significant difference between the M and NM groups in the 32 randomised LD patients. Continuing treatment during remission with agents used to induce the remission can prolong survival in patients with extensive stage ASCB.

Occupational asthma due to methyl methacrylate and cyanoacrylates.

Five patients had asthma provoked by cyanoacrylates and one by methyl methacrylate, possibly because of the development of a specific hypersensitivity response. Acrylates have wide domestic as well as industrial uses, and inhalation of vapour emitted during their use can cause asthma.