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Biomedical subjects

L B Irving

Publications and source records attributed to L B Irving.

16 recordsLinked to original sources
PubMed2004

Screening for lung cancer.

BACKGROUND: While population based screening for lung cancer has not been adopted by most countries, it is not clear whether sputum examinations, chest radiography or newer methods such as computed tomography are effective in reducing mortality from lung cancer. OBJECTIVES: To determine whether screening for lung cancer using regular sputum examinations or chest radiography or CT chest reduces lung cancer mortality. SEARCH STRATEGY: Electronic databases (the Cochrane Central Register of Controlled Trials, MEDLINE, PREMEDLINE and EMBASE; 1966 to July 2000) ), bibliographies, hand searching of a journal and discussion with experts were used to identify published and unpublished trials. SELECTION CRITERIA: Controlled trials of screening for lung cancer using sputum examinations, chest radiography or CT chest. DATA COLLECTION AND ANALYSIS: Intention to screen analysis was performed. Where there was significant statistical heterogeneity relative risks were reported using the random effects model, but for other outcomes the fixed effect model was used. MAIN RESULTS: Seven trials were included (6 randomised controlled studies and 1 non-randomised controlled trial) with a total of 245,610 subjects. There were no studies with an unscreened control group. Frequent screening with chest x-rays was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, CI: 1.00-1.23). A non statistically significant trend was observed to reduced mortality from lung cancer when screening with chest x-ray and sputum cytology was compared with chest x-ray alone (RR 0.88, CI:0.74-1.03). Several of the included studies had potential methodological weaknesses. There were no controlled studies of spiral CT. REVIEWER'S CONCLUSIONS: The current evidence does not support screening for lung cancer with chest radiography or sputum cytology. Frequent chest x-ray screening might be harmful. Further, methodologically rigorous trials are required.

Adult↗
PubMed2003

Screening for lung cancer: a systematic review and meta-analysis of controlled trials.

BACKGROUND: Lung cancer is a substantial public health problem in western countries. Previous studies have examined different screening strategies for lung cancer but there have been no published systematic reviews. METHODS: A systematic review of controlled trials was conducted to determine whether screening for lung cancer using regular sputum examinations or chest radiography or computed tomography (CT) reduces lung cancer mortality. The primary outcome was lung cancer mortality; secondary outcomes were lung cancer survival and all cause mortality. RESULTS: One non-randomised controlled trial and six randomised controlled trials with a total of 245 610 subjects were included in the review. In all studies the control group received some type of screening. More frequent screening with chest radiography was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, 95% CI 1.00 to 1.23). A non-statistically significant trend to reduced mortality from lung cancer was observed when screening with chest radiography and sputum cytological examination was compared with chest radiography alone (RR 0.88, 95% CI 0.74 to 1.03). Several of the included studies had potential methodological weaknesses. Controlled studies of spiral CT scanning have not been reported. CONCLUSIONS: The current evidence does not support screening for lung cancer with chest radiography or sputum cytological examination. Frequent chest radiography might be harmful. Further methodologically rigorous trials are required before any new screening methods are introduced into clinical practice.

Controlled Clinical Trials as Topic↗
PubMed2001

Screening for lung cancer.

BACKGROUND: The effectiveness of screening for lung cancer with chest radiography, sputum cytology or spiral CT has not been established. OBJECTIVES: To determine whether screening for lung cancer using regular sputum examinations or chest radiography or CT chest reduces lung cancer mortality. SEARCH STRATEGY: Electronic databases, bibliographies, hand searching of a journal and discussion with experts were used to identify published and unpublished trials. SELECTION CRITERIA: Controlled trials of screening for lung cancer using sputum examinations, chest radiography or CT chest. DATA COLLECTION AND ANALYSIS: Intention to screen analysis was performed. Where there was significant statistical heterogeneity relative risks were reported using the random effect model, but for other outcomes the fixed effect model was used. MAIN RESULTS: Seven trials were included (6 randomised controlled studies and 1 non-randomised controlled trial) with a total of 245,610 subjects. There were no studies with an unscreened control group. Frequent screening with chest x-rays was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, CI: 1.00-1.23). A non statistically significant trend was observed to reduced mortality from lung cancer when screening with chest x-ray and sputum cytology was compared with chest x-ray alone (RR 0.88, CI:0.74-1.03). Several of the included studies had potential methodological weaknesses. There were no controlled studies of spiral CT. REVIEWER'S CONCLUSIONS: The current evidence does not support screening for lung cancer with chest radiography or sputum cytology. Frequent chest x-ray screening might be harmful. Further, methodologically rigorous trials are required.

Adult↗
PubMed1997

Recent advances in managing non-small-cell lung cancer: 1. Clinical aspects of diagnosis and staging.

Lung cancer is the leading cause of death from cancer in Australian adults. Over 90% of lung cancers are due to exposure to tobacco smoke. Female smokers are more susceptible to developing lung cancer than male smokers. The overall survival of non-small-cell lung cancer is 13%, having increased from 6% over the past 30 years. The development of new, unexplained respiratory or systemic symptoms in a heavy smoker or ex-smoker should raise the suspicion of lung cancer. Early detection and consideration of tumour resection for all operable tumours are the main strategies for improving the cure rate of non-small-cell lung cancer at present. Reducing the prevalence of smoking remains the best method for reducing lung cancer deaths.

Adult↗
PubMed1997

Frequent loss of heterozygosity in early non-small cell lung cancers at chromosome 9p21 proximal to the CDKN2a gene.

Deletions involving the chromosome 9p21 region have been reported as frequent events in non-small cell lung cancer (NSCLC). To investigate potential tumor-suppressor gene (TSG) loci within the 9p21 region, which also harbors the candidate TSG locus CDKN2a, we studied 32 cases of primary NSCLC for loss of heterozygosity (LOH). Tumor and paired normal lung cells were microdissected from lung tissue imprints and all samples screened using PCR-LOH analysis with 15 9p markers. In addition, 3 NSCLC cell lines and their matched normal lung and tumor DNA were similarly analyzed. LOH at the marker D9S259, which is proximal to the CDKN2a locus, was found most frequently (52%), while LOH at D9S942, the marker closest (5 kb) to the CDKN2a gene, was seen in only 17%. Homozygous loss of markers close to CDKN2a was, however, detected in 2 of the 3 cell lines and one accompanying tumor sample. We propose that a TSG in the region of deletion proximal to the CDKN2a gene within 9p21 may play a significant role in the pathogenesis and progression of NSCLC.

Carcinoma, Non-Small-Cell Lung↗
PubMed1997

Resolution of gas exchange abnormalities and intrapulmonary shunting following liver transplantation.

This prospective study evaluated pulmonary gas exchange in patients with severe liver disease, its relationship to intrapulmonary shunting, and its response to liver transplantation. Detailed clinical examinations, chest radiographs, and arterial blood gas estimations were performed on 74 consecutive patients before and after liver transplantation. Fifty percent of the 74 patients had a widened alveolar-arterial (A-a) oxygen gradient (> 15 mm Hg) and 45% a reduced PaCO2 (< 35 mm Hg). Twenty-two percent were hypoxemic (PaO2 < 80 mm Hg). Following transplantation mean PaO2 increased (pre-89 +/- 14 vs. post-94 +/- 8 mm Hg; P = .014) and A-a oxygen gradient decreased (pre-16 +/- 14 vs. post-8 +/- 9 mm Hg; P < .001), despite an increase in PaCO2 (pre-36 +/- 5 vs. post-39 +/- 4; P < .001). To examine this improvement in oxygen exchange further, a subgroup of 26 consecutive patients, with no obvious cardiorespiratory cause for abnormal gas exchange underwent, pre- and post-operative spirometry, measurement of carbon monoxide diffusion capacity (DLCO), intrapulmonary shunt estimations (100% oxygen technique), and echocardiography. In this subgroup, 23% were hypoxemic, 54% had a widened A-a oxygen gradient, and 85% had increased intrapulmonary shunting (> 5%) before transplantation. There was a significant correlation between the degree of pre-transplantation intrapulmonary shunting and A-a oxygen gradient (P < .01). Nineteen of the 22 patients with increased shunting improved following transplantation and improved A-a oxygen gradient correlated well with the reduction in shunting (P < .005). DLCO was reduced in 69% of these patients with a mean value of 73% of predicted. However, the post-transplantation mean DLCO did not increase despite the improvement in oxygen exchange. In conclusion, gas exchange abnormalities are common in patients with severe liver disease but these usually resolve post-transplantation. Intrapulmonary shunting is a major determinant of abnormal oxygen uptake in transplant candidates without evidence of cardiorespiratory disease. Finally, the mechanism for the reduced DLCO is unclear but appears different to that responsible for intrapulmonary shunting and abnormal oxygen exchange.

Adult↗
PubMed1997

Influenza vaccination: cost-effective health care for the older adult?

Influenza is a serious cause of morbidity and mortality, particularly in the older adult, and it represents a significant economic burden for health-care services. We have reviewed the published literature relating to influenza vaccine effectiveness and the cost-effectiveness of influenza vaccination in comparison with other health-care interventions and conclude that influenza vaccination is one of the most cost-effective interventions possible in the older adult population.

Adolescent↗
PubMed1996

Surface CD4 is critical to in vitro HIV infection of human alveolar macrophages.

The CD4 glycoprotein is the major cellular receptor for HIV. CD4 surface expression of monocytes decreases with time in culture while their susceptibility to HIV-1 increases. Our aim was to investigate whether this phenomenon occurs in macrophages that have differentiated in vivo by investigating CD4 expression and HIV-1 infection of human alveolar macrophages (AMs). Using flow cytometry to detect CD4 expression by Leu-3a labeled indirectly with fluorescein isothiocyanate or allophycocyanin, we found that CD4 was expressed at low but detectable levels, despite the high background autofluorescence well described in AMs. This finding was supported by the detection of CD4 mRNA in AMs using RT-PCR. T cell contamination of mRNA extracts of AMs was excluded by amplifying in parallel with primers to the constant region of the T cell receptor. Despite this low level of surface CD4, recombinant soluble CD4 and anti-CD4 antibody completely inhibited HIV-1 infection of AMs. We conclude that CD4, although expressed at low levels on the surface of AMs, appears to be critical to HIV-1 infection of these cells.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Treatment principles in advanced non-small-cell lung cancer.

Non-small-cell lung cancer (NSCLC) accounts for more than three quarters of all lung tumours and is the leading cause of deaths due to cancer in Australia. More than half of the patients with NSCLC present with advanced disease. Radiation therapy has been the mainstay of active treatment for these patients. There is increasing evidence supporting the benefit of chemotherapy as an addition to radiation therapy in locally advanced non-metastatic disease. The use of cisplatin-based chemotherapy prior to radiation therapy would appear to be a new standard of care in patients with stage III B NSCLC. In advanced (metastic) disease, palliation of symptoms remains the major goal of current treatment programmes. This can be achieved with the best supportive care, radiotherapy, and, in selected patients, platinum-based chemotherapy. Clinical trials to test new treatments, with survival, quality of life and cost-benefit as endpoints, are essential. The present study discusses the current status of conventional and newer treatment methods in locally advanced and metastatic disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Is normobaric simulation of hypobaric hypoxia accurate in chronic airflow limitation?

Hypobaric hypoxemia is experienced by passengers during commercial aircraft flight. In order to assess the extent of hypoxemia and to test whether hypobaric hypoxia can be accurately estimated at sea level, the results of the normobaric hypoxia altitude simulation test (N-HAST) were compared with those of the hypobaric hypoxia altitude simulation test (H-HAST) in six normal control subjects and nine patients with chronic airflow limitation (CAL) at simulated cabin altitudes of 6,000 ft (1,829 m) and both at rest and during exercise at 8,000 ft (2,438 m). Serial arterial blood samples were drawn during the breathing of 15.1 and 16.3% inspired oxygen at sea level (N-HAST) at rest and during light exercise, and during the breathing of room air at simulated cabin altitudes (H-HAST) of 609 mm Hg (6,000 ft) and 565 mm Hg (8,000 ft) at rest and during light exercise. As measured with the H-HAST technique, the mean (+/- SD) PaO2 of the normal group fell from 96.2 +/- 6.2 mm Hg (sea level) to 70.1 +/- 6.0 mm Hg (6,000 ft), and to 61.7 +/- 1.6 mm Hg (8,000 ft at rest) and 54.8 +/- 7.1 mm Hg (8,000 ft during exercise) (p < 0.005 by analysis of variance [ANOVA]). In the CAL group, the mean (+/- SD) PaO2 fell from 75.8 +/- 8.2 mm Hg (sea level) to 57.0 +/- 6.3 mm Hg (6,000 ft), and 49.5 +/- 6.1 mm Hg (8,000 ft at rest), and 38.6 +/- 7.5 mm Hg (8,000 ft during exercise) (p < 0.005 by ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Homozygous and hemizygous deletions of 9p centromeric to the interferon genes in lung cancer.

Cytogenetic analysis has indicated that deletion of chromosome 9p occurs in a significant number of non-small cell lung and mesothelioma tumors. Using paired oligonucleotide primers, we have undertaken an extensive analysis of 9p markers to determine homozygous and heterozygous loss of marker sequences. Homozygous loss of D9S169 and D9S171, both of which map centromeric to the IFN gene cluster, were noted in three cell lines (27%) and hemizygous deletions of one or both of these loci was found in a further six cell lines (54%). These data suggest the presence of a potential tumor suppressor gene for lung cancer in proximity to D9S169 and D9S171 at 9p21.

Carcinoma, Non-Small-Cell Lung↗
PubMed1989

Dietary and alcohol intake, smoking pattern, occupational risk, and family history in lung cancer patients: results of a case-control study in males.

In a case-control study of 71 consecutive new male cases of lung cancer and 71 male hospital control patients, previous dietary and alcohol intake, smoking pattern, occupation, dust exposure, and family history of lung cancer were investigated. The cases and controls were similar in age, country of origin, area of residence, and marital status. Using a frequency-based assessment of previous dietary intake, broad food groups were similar for cases and controls. Cases had a significantly lower intake of fish than controls did (odds ratio = 0.5, confidence interval = 0.2-1.0, p = 0.05). A protective effect for fish consumption in lung cancer has not been previously reported. The dietary intake of foods containing retinol and beta-carotene and the intake of alcohol were not significantly different between cases and controls. For cases, smoking duration was longer and the time since cessation for exsmokers was shorter, cigarette pack years were longer, and the number of cigarettes smoked per day was greater. The factors of occupation, dust exposure, and family history of cancer (including lung cancer) were similarly distributed between cases and controls.

Adenocarcinoma↗
PubMed1988

Heterogeneous proliferative characteristics of human adult lung fibroblast lines and clonally derived fibroblasts from control and fibrotic tissue.

Pulmonary fibrosis results from an altered deposition of collagen within the lung parenchyma. This alteration is likely the result of both increased fibroblast proliferation and abnormalities in fibroblast collagen metabolism. Although the development of pulmonary fibrosis is preceded by inflammatory events in the lung, it is unclear whether altered fibroblast behavior requires continuous exposure to inflammatory mediators or alternatively results from the emergence in the lung of fibroblast populations possessing characteristics such as to explain the abnormalities seen in pulmonary fibrosis. To examine the latter hypothesis, we have established a number of fibroblast cell lines from control (C) lung tissue as well as from tissue from patients with active pulmonary fibrosis (PF), and have examined their in vitro proliferative characteristics. Our data show that PF fibroblasts proliferate significantly faster compared to C fibroblasts under standard culture conditions. We have also examined the in vitro proliferative characteristics of a substantial number of clonally derived fibroblasts. We report that a marked heterogeneity exists in terms of proliferation and also that a small but significant number of fast-growing clones are present in panels of clones derived from fibrotic tissue. These data suggest that there exists in fibrotic tissue, clones of fibroblasts with intrinsic growth characteristics which could in itself explain the increased fibroblast proliferation seen in pulmonary fibrosis. The fibrotic clones may emerge as dominant in the fibrotic lung under conditions of injury and repair likely to favor the expansion of this phenotype.

Adult↗
PubMed1988

Spontaneous in vitro release of alveolar-macrophage cytokines after the intratracheal instillation of bleomycin in rats. Characterization and kinetic studies.

The intratracheal administration of bleomycin in rats elicits an acute inflammatory response in the lung followed by the development of pulmonary fibrosis. The alveolar macrophage (AM) is a key effector cell involved in this process because of its potential to release a variety of hormonelike molecules (cytokines) that can modulate systemic responses as well as the local response of other lung cells including the interstitial fibroblast. In this report, we have documented the chronology of the in vitro spontaneous release of AM cytokines after a single instillation of bleomycin. We show that supernatants from AM harvested after the administration of bleomycin but not after saline contain lymphocyte-activating factor (interleukin-1) activity. Maximal activity was detected between 6 and 12 h and was barely detectable by Day 7 after bleomycin. In addition, supernatants showing interleukin-1 (IL-1) activity also inhibited the proliferation of log-phase normal rat lung fibroblasts. Fractionation of supernatants from AM harvested 6 h after bleomycin demonstrated that both lymphocyte-activating factor and fibroblast modulatory activity coelute in the same 18-kDa region, suggesting that IL-1 may demonstrate both activities. We also report here the spontaneous release of a second AM cytokine, hepatocyte-stimulating factor, which we have recently shown in humans to be identical to interferon beta 2 and which initiates the hepatic acute-phase protein response. The release of this 30-kDa cytokine from AM of rats exposed to bleomycin has a different chronology than does IL-1, showing a steady increase over time, with maximal activity at Day 28 after bleomycin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Solute movement across the alveolar-capillary membrane after intratracheally administered bleomycin in rats.

The rate of absorption across the alveolar-capillary membrane of inhaled 99mTc-DTPA and the concentration of albumin in the bronchoalveolar lavage (BAL) fluid were characterized in a rat model of bleomycin-induced pulmonary fibrosis. Adult male Lewis rats were studied from 1 h to 120 days after a single intratracheal instillation of bleomycin (0.5 to 0.6 U/100 g body weight). The retention of 99mTc-DTPA in the lungs, expressed as a percentage of the baseline radioactivity, was determined at 15 min (%R15) after delivery of the tracer. The %R15 was 83.7 +/- 6.0 for normal untreated rats and 84.3 +/- 3.7 for saline-treated animals. The rate of absorption of 99mTc-DTPA began to increase 24 h after bleomycin, reaching a maximum at Day 7, with %R15 = 56.0 +/- 6.5 (p less than 0.0001). Resolution to control values occurred by Day 34 after bleomycin. At Day 45 after bleomycin, the rate of absorption of 99mTc-DTPA was slower than sham (control), with %R15 = 89.2 +/- 1.9 (p less than 0.5). However, from Day 63 onwards, removal was not different from control. The concentration of albumin in the BAL fluid began to increase 48 h after bleomycin, was 10-fold greater than control by Day 7 (150 +/- 38 versus 16 +/- 3 micrograms/ml), and returned to control values by Day 28. The percentage of neutrophils in the BAL increased at 12 h, reached a plateau of 33 +/- 9% between 4 and 7 days, and then returned to control values by Day 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗