Occupational inhalant exposure and respiratory disorders among never-smokers referred to a hospital pulmonary function laboratory

BACKGROUND: Multiple reports have described associations between occupational inhalant exposure and lung disease. Previous occupational lung disease investigations have studied populations consisting of both smokers and nonsmokers. Smoking complicates interpretation of toxicant exposure-response relationships. The objective of this study was to determine whether, among never-smokers, occupational exposure to gases, dusts, or fumes is associated with a history of respiratory disorders and pulmonary function test defined obstructive lung disease. METHODS: We performed a retrospective analysis of 517 never-smoker patients who underwent pulmonary function testing in our clinical laboratory between 1986 and 1999. We calculated the relative risks of developing adverse respiratory health outcomes given a history of exposure to occupational inhalants. RESULTS: Compared with persons with a negative occupational exposure history, exposed persons had an increased risk of reporting a history of bronchitis [relative risk (RR), 1.59; 95% confidence interval (CI), 1.20-2.12], recurrent lung infections (RR, 2.09; 95% CI, 1.14-3.82), and bronchodilator use (RR, 1.61; 95% CI, 1.26-2.06). There was also a statistically significant association between a history of inhalant exposure and the finding of an obstructive ventilatory defect on pulmonary function testing (RR, 1.79; 95% CI, 1.12-2.85). A history of inhalant exposure was not associated with self-reported asthma (RR, 1.08; 95% CI, 0.83-1.41). The population attributable risk estimates for respiratory disorders due to inhalant exposure were: bronchitis, 23.6%; recurrent lung infection, 36.3%; bronchodilator use, 24.3%; and obstructive lung disease, 29.6%. CONCLUSIONS: Occupational inhalant exposure is a strong risk factor for lung disease in this population of never smokers. A significant burden of respiratory disease in this population may be attributable to occupational inhalant exposure.     

Lack of association between skin tags and colon polyps in a primary care setting

Cutaneous skin tags (acrochordons) have recently been proposed as markers for adenomatous polyps of the colon among symptomatic patients referred for colonoscopy. To ascertain the utility of skin tags as a predictor of colonic polyps in a primary care setting, 492 patients, with a mean age of 58 +/- 13.3 years (241 with signs or symptoms and 251 for screening), were evaluated for the presence of skin tags and then examined using a 60-cm fiberoptic sigmoidoscope by an examiner "blinded" to the skin findings. Among patients with skin tags, 23 (10.2%) of 226 had polyps, whereas among patients without skin tags, 20 (7.5%) of 266 had polyps. The predictive value of the presence of a skin tag was 10.2%. Contrary to studies done in more selected populations with a higher prevalence of adenomatous polyps, the results using a 60-cm flexible sigmoidoscope in a primary care population suggest that cutaneous skin tags are not a marker for adenomatous polyps of the colon.     

Long-term insulin treatment of 3T3-L1 adipocytes results in mis-targeting of GLUT4: implications for insulin-stimulated glucose transport

Aims/hypothesis. Insulin stimulates glucose transport in adipose and muscle tissue by the translocation of a specialised pool of intracellular GLUT4-containing vesicles to the cell surface. It is well established that defective insulin-stimulated GLUT4 translocation is associated with insulin resistance. Long-term insulin treatment (500 nmol/l for 24 h) of 3T3-L1 adipocytes has previously been shown to decrease cellular GLUT4 content and reduce insulin-stimulated GLUT4 translocation. Here, we test the hypothesis that the insulin resistance observed after long-term insulin treatment arises by the selective loss of GLUT4 from a specific intracellular compartment.¶Methods. Using iodixanol gradient centrifugation we have separated intracellular GLUT4 containing membranes into two distinct populations corresponding to recycling endosomes and a distinct intracellular compartment which probably represents GLUT4 storage vesicles (GSVs).¶Results. A short-term insulin stimulation reduced the content of GLUT4 in the GSV fraction (51 ± 3.5 %) with only a modest decrease from the endosomal fraction (23 ± 2.6 %). Long-term insulin treatment decreased cellular GLUT4 content by about 40 % and diminished the ability of a short-term insulin challenge to promote GLUT4 translocation. We further show that this depletion of cellular GLUT4 is selectively from the GSV fraction (68 ± 7 % decrease compared to untreated cells).¶Conclusions/interpretation. Such data argue that long-term insulin treatment results in the mis-targeting of GLUT4 such that it no longer accesses the GSV compartment. These data imply that defective targeting of GLUT4 away from the GSV compartment plays an important role in the aetiology of insulin resistance. [Diabetologia (2000) 43: 1273–1281]     

Phorbol ester effects on neurotransmission: interaction with neurotransmitters and calcium in smooth muscle.

Stimulation of the phosphatidylinositol cycle by neurotransmitters generates diacylglycerol, an activator of protein kinase C, which may regulate some forms of neurotransmission. Phorbol esters, potent inflammatory and tumor-promoting compounds, also activate protein kinase C. We demonstrate potent and selective effects of phorbol esters on smooth muscle, indicating a role for protein kinase C in neurotransmission. In rat vas deferens and dog basilar artery, phorbol esters synergize with calcium to mimic the contractile effects of neurotransmitters that act through the phosphatidylinositol cycle. In guinea pig ileum and rat uterus, phorbol esters block contractions produced by these neurotransmitters.     

Breathing pattern and eye movement density during REM sleep in humans

Changes in the density of eye movement during rapid eye movement (REM) sleep are associated with changes in ventilation and ventilatory response in animals. Recent data in patients with chronic obstructive pulmonary disease suggest that periods of frequent eye movements may be associated with hypoxemia during REM sleep. We have therefore investigated the association between eye movements and ventilation and ventilatory pattern in 10 normal men. Expired ventilation was measured using a pneumotachograph attached to a valved face mask with a dead space of 50 ml and incorporating a peripheral CO2 leak detector. Ventilation was reduced (p less than 0.02) in all stages of sleep compared with that during wakefulness, with no difference between the level of ventilation in each sleep stage (awake, 7.18 +/- 0.43 SEM; Stage 2, 6.47 +/- 0.43; Stage 3/4, 6.45 +/- 0.52; REM sleep, 6.55 +/- 0.47 L/min). During REM sleep, eye movements (EMs) were associated with rapid shallow breathing. Dividing REM into 20-s epochs with or without EMs, EMs were associated with a raised breathing frequency (no EMs, 14.4 +/- 0.4 breaths/min; EMs, 15.8 +/- 0.5 breaths/min; p = 0.01), reduced tidal volume (0.49 +/- 0.03 L; 0.41 +/- 0.03 L; p less than 0.01), and reduced minute ventilation (6.87 +/- 0.45 L; 6.27 +/- 0.51 L; p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

A sensor for needle puncture force measurement during interventional radiological procedures

Computer-based simulation for interventional radiology training has attracted increasing attention in recent years because of its potential to train remotely from patients and to provide objective assessment of proficiency. Yet developing a high fidelity simulator with realistic tactile feedback requires accurate knowledge of forces exerted on medical devices during interventional radiology procedures. This paper presents the development and validation of a force sensor for the measurement of axial forces generated during needle, and combined cannula/trocar, puncture procedures in patients. In order to assess the performance of this sensor, in vitro measurements were obtained using needle penetration of porcine liver, kidney and muscle. The results were compared with forces measured by means of a tensile tester.Calibration results showed that the force sensor has high sensitivity and linearity. Comparison of the force profiles obtained from the sensor and the tensile tester shows that good agreement was achieved in the in vitro studies for all the tissues tested.Preliminary clinical force measurements during arterial puncture and liver biopsy procedures have been performed in patients. An example of force recording for each procedure type is presented.