Decreased FEV1 % in asthmatic adults in Scottish homes with high Environmental Relative Moldiness Index values.

BACKGROUND: Exposures to indoor biological contaminants have been implicated in asthma's aetiology but their effect on lung function is not well quantified. OBJECTIVE: The aim of this cross-sectional study of non-smoking, asthmatic adults in Scotland was to determine the correlation between the results from a standard spirometry test, forced expiratory volume in one-second percent (FEV1 %), and quantitative estimates of some biological exposures. METHODS: A population (n = 55) of non-smoking, adult asthmatics in Scotland was included in this study and each completed a questionnaire that allowed the determination of the Asthma Control Questionnaire scores (ACQ) and St. George's Respiratory Questionnaire scores (SGRQ), as well as corticosteroid use. Spirometry testing was completed and the pre-bronchodilator FEV1 % value calculated. At about the same time, floor dust samples were collected in the living room and in the bedroom. These dust samples were analysed for mould contamination, as described by the Environmental Relative Moldiness Index (ERMI) values and by (1, 3)-ß-D-glucan concentrations, for endotoxin, and for dust mite, cat, and dog allergen concentrations. The asthmatics' FEV1 % values were tested for correlation (Pearson) to questionnaire-based estimates of health. Also, each biological exposure was tested for correlation (Pearson) to the FEV1 % values. RESULTS: FEV1 % results were correlated with ACQ scores (ρ -0.586, P < 0.001), SGRQ scores (ρ -0.313, P = 0.020), and weakly with corticosteroid use (ρ -0.221, P = 0.105). The ERMI values in the homes (average 5.3) were significantly correlated with FEV1 % values (ρ -0.378, P = 0.004). There was no correlation between FEV1 % and concentrations of endotoxin, (1, 3)-ß-D-glucan, or any of the allergens. CONCLUSION AND CLINICAL RELEVANCE: Although these results do not prove that mould exposures caused the deficit in lung function observed in this study, it might be advisable for asthmatics to avoid high ERMI environments.

Effect of improved home ventilation on asthma control and house dust mite allergen levels.

BACKGROUND: The warm, humid environment in modern homes favours the dust mite population, but the effect of improved home ventilation on asthma control has not been established. We tested the hypothesis that a domestic mechanical heat recovery ventilation system (MHRV), in addition to allergen avoidance measures, can improve asthma control by attenuating re-colonization rates. METHODS: We conducted a randomized double-blind placebo-controlled parallel group trial of the installation of MHRV activated in half the homes of 120 adults with asthma, allergic to Dermatophagoides pteronyssinus. All homes had carpets steam cleaned and new bedding and mattress covers at baseline. The primary outcome was morning peak expiratory flow (PEF) at 12 months. RESULTS: At 12 months, the primary end-point; change in mean morning PEF as compared with baseline, did not differ between the MHRV group and the control group (mean difference 13.5 l/min, 95% CI: -2.6 to 29.8, P = 0.10). However, a secondary end-point; evening mean PEF, was significantly improved in the MHRV group (mean difference 24.5 l/min, 95% CI: 8.9-40.1, P = 0.002). Indoor relative humidity was reduced in MHRV homes, but there was no difference between the groups in Der p 1 levels, compared with baseline. CONCLUSIONS: The addition of MHRV to house dust mite eradication strategies did not achieve a reduction in mite allergen levels, but did improve evening PEF.

A comparison of epidermal growth factor receptor (EGFR) and c-erbB-2 oncogene expression in head and neck squamous cell carcinomas.

The proto-oncogenes c-erbB-2 and epidermal growth factor (EGF) receptor which encode 2 closely homologous transmembrane glycoproteins have been found amplified and/or overexpressed in a range of epithelial malignancies. In a series of 46 head and neck squamous cell cancers (SCCs), immunohistochemical reactivity for the EGF receptor was detected in all cases, particularly at the invading edge of cellular islands of SCC and in the basal cells of normal adjacent squamous epithelium. Southern blot analysis demonstrated EGF receptor gene amplification in 3 cases. In contrast, strong membrane staining for the c-erbB-2 oncoprotein was not detected in any sample, and there were no cases of c-erbB-2 gene amplification. Despite a close structural and (presumed) functional homology between these 2 receptor-oncoproteins in the development of malignancy, we report that their expression in SCCs is markedly different. Furthermore, unlike the situation for breast cancer, quantitation of the c-erbB-2 or EGF receptor oncoproteins is unlikely to yield important prognostic information in this group of patients.

Respiratory gas exchange during positive pressure breathing and rapid decompression to simulated altitudes of 18.3 and 24.4 km.

Respiratory gas exchange was studied, using the technique of mass spectrometry, during events of slow and rapid decompression of human subjects to simulated altitudes of 60,000 and 80,000 ft (18.3 and 24.4 km, respectively). Positive breathing pressures and G-suit counterpressures were employed in three series of decompression experiment. Low levels of inspired carbon dioxide and nitrogen reflected the rebreathing of gases throughout the experiments. Application of a positive breathing pressure of 70 torr, accompanied by a jerkin pressure equal to breathing pressure and a G-suit counterpressure of four times the breathing pressure on the trunk and limbs, respectively, maintained alveolar oxygen at physiologically safe levels during decompression to 60,000 ft (18.3 km) altitude. Similarly, 80 torr positive breathing pressure, in combination with four times the breathing pressure in the G suit, adequately satisfied the requirements for oxygen during rapid decompression to 80,000 ft (24.4 km) simulated altitude.

Protection against the physiological effects of positive pressure breathing.

The degree of protection afforded by three jerkin G-suit systems (British, Canadian and Swedish) using different pressures against the adverse physiological effects produced by high levels (50 mm Hg and 70 mm Hg) of positive pressure breathing (PPB) was investigated at ground level in 10 male subjects. The British and Canadian systems were evaluated with G-suit pressure equal to breathing pressure and 3.2 times breathing pressure, whereas the Swedish system was studied only with 3.2 times breathing pressure in the G suit. The experimental design was a 10 X 10 Latin swuare. PPB produced significant increases in heart rate, peripheral resistance, and systolic, diastolic and mean arterial blood pressures, and significant decreases in stroke volume and cardiac output. These effects were directly related to the level of PPB. Our results show that the British system provides the highestdegree of protection against PPB, followed by the Swedish and the Canadian systems. It was also found that a G-suit pressure of 3.2 times breathing pressure significantly increases the degree of protection afforded by the British and Canadian systems.

Carbon monoxide exposure and auditory duration discrimination.

Two young adults performed an auditory duration discrimination task while sitting in an open office (i.e., without sensory isolation). The percentage of errors rose when carboxyhemoglobin (HbCO) readings of 3.2% or 4.7% were produced by a rebreathing method; there was a parallel but statistically insignificant trend at 2.0% HbCO. Analysis of the data by psychophysical measures, however, showed no significant changes of difference threshold, criterion value, or point of subjective equality. After the tape was rearranged to meet criteria of a constant interval, a balanced order of presentation, and psychological rather than physical equality of tone length, eight young adults performed the task better in an isolation booth than in an open office, scores in both situations being unaffected by increases of HbCO to greater than 8%. Further trials with five young adults compared responses before and after administration of 80 ml of CO (HbCO 4.92%); again, no effect of carbon monoxide was seen relative to control experiments. The error score of nonsmoking young adults can be increased by a level of HbCO as low as 3.2%. The likelihood of such a response, however, is markedly influenced by task difficulty, environment, and the arousal of the subjects. Furthermore, the nature of the functional disturbance remains uncertain; psychophysical measures show no significant impairment of auditory duration discrimination.

Brake reaction time--effects of age, sex, and carbon monoxide.

Simulated braking responses have been tested in relation to blood carboxyhemoglobin (HbCO) levels. The main determinants of percentage of HbCO in 352 subjects attending a fall fair were daily cigarette consumption and minutes since the last cigarette. In women the brake response time deteriorated from age 16 yr, but in the men there was an improvement from age 16 to the early 20s. Times at all ages were better for men than for women. Average response times and the rate of aging of the braking response were very similar in smokers and in nonsmokers. In the nonsmokers, however, response time with step function CO increments of as much as 7% HbCO. There was a suggestion of a small increase of reaction time, with an opposing decrease of leg movement time, during the first few minutes after CO exposure; nevertheless, these trends were statistically insignificant.

Carbon monoxide in the urban atmosphere: hazards to the pedestrian and the street-worker.

The carbon monoxide (CO) concentrations encountered by pedestrians and workers in the streets of a large metropolis were monitored by a reliable and sensitive portable detector (the Ecolyzer). Up to 1,000 observations per day were collected for several months during the summer and fall of 1973. The CO levels ranged from 10 to 50 ppm (varying with wind speed and direction, atmospheric stability, traffic density, and the height of nearby buildings). Much higher average concentrations were found in such adverse sites as poorly ventilated underpasses and underground garages. Street closures for a pedestrian mall reduced levels on the mall to around the general urban background withoug large increases in readings on adjoining streets. Many street-workers have little medical supervision, and for this reason the urban eight-hour CO ceilings may be a more appropriate air quality target than the usual industrial figure of 50 ppm. However, even the latter is sometimes exceeded on busy city streets.

Carbon monoxide, nicotine and the 'safer' cigarette.

15 healthy adults (5 women, 10 men) have been exposed to each of four experimental conditions: rebreathing of air or carbon monoxide, and the smoking of two low-nicotine (0.3 mg) or medium-nicotine (1.2 mg) cigarettes. The dose of carbon monoxide selected (80 ml) had no effect on resting heart rate or electrocardiogram, nor did it modify the exercise heart rate, ventilation, oxygen consumption or electrocardiogram. Both types of cigarette produced variable changes in the blood carboxyhaemoglobin level, increments being greatest in heavy smokers, and least in former smokers, pipe and cigar smokers, Gains of carboxyhaemoglobin were less with low-nicotine than with medium-nicotine cigarettes. Both types of cigarette produced some increase of resting heart rate, but the smoking of two cigarettes was insufficient to modify the exercise heart rate, ventilation, or oxygen consumption. The electrocardiogram also showed no signs of ischaemia during either rest or effort. It is suggested that, for the light and moderate smoke, the 'safest' cigarette may be one with a low tar and a very low nicotine yield. On the present data, this would also induce only small increments of blood carboxyhaemoglobin levels.

Pharmacokinetics of antipyrine, warfarin and paracetamol in the brushtail possum.

The plasma pharmacokinetics of antipyrine, warfarin and paracetamol have been studied in the Australian brushtail possum (Trichosurus vulpecula). The plasma elimination half-lives (t1/2) were 1.2 h for antipyrine, 11.9 h for warfarin and 5.2-12.9 h for paracetamol. Our data indicate that the clearance of these three xenobiotics in the possum is similar to that reported in eutherian mammals. There was no dose-dependent increase in paracetamol plasma t1/2 over the dose range 100-1000 mg kg(-1), indicating a lack of capacity saturation. This observation may in part explain the unusual resistance of the possum to the hepatotoxic effect of high doses of paracetamol.

Rehabilitation of the injured worker.

The Workers' Compensation Board is mostly involved in secondary and tertiary prevention of work-related accidents and disease. Through its new Medical Rehabilitation Strategy, the board will help to ensure that optimal health care programs are available to injured workers. For workers who are left with restricted function, even after the best possible health care, vocational rehabilitation or tertiary prevention programs are offered. In both phases the primary care physician has a key function and must be familiar with the "state of the art" treatment of so-called minor trauma and activity-related disorders. Physicians also must recognize the importance of providing a reasonable prognosis as early as possible because it will drive the vocational rehabilitation planning process.

Narcotic effects of nitrous oxide and compressed air on memory and auditory perception.

Three experiments were conducted to examine the effects of 35% N2 O (nitrous oxide) on human memory and auditory perception. In Experiment I, dichotic listening performance was found to be impaired. Experiment II used the same technique but was controlled for attenuation of sound transmission in the middle ear. No impairment was found. The perceptual effect found in Experiment I was peripheral, not central, and N2O did not impair short-term memory (STM). Experiment III used one-trial free recall of a word list. The shapes of the serial position curves were interpreted as indicating that N2O impairs long-term memory (LTM) but not STM. Experiment III provided no evidence, using cued recall, that the LTM deficit was due to impaired retrieval. Comparing these results with those for compressed air led to the conclusion that both N2O and hyperbaric nitrogen display an identical pattern of effects. A reason for the decrement found in some N2O STM studies may have been confounding the measurement of STM with that of LTM.

Hormone therapy in women in the menopause transition. Randomised, double-blind, placebo-controlled trial of effects on body weight, blood pressure, lipoprotein levels, antithrombin III activity, and the endometrium.

OBJECTIVE: To determine whether hormone treatment of women during the menopause transition induces changes in body weight, blood pressure, lipoprotein levels, antithrombin III activity, and the endometrium. DESIGN: Prospective, randomised, placebo-controlled, double-blind, 12-month study, with crossover at 6 months. SETTING: Outpatient clinic of a city hospital. PARTICIPANTS: 105 apparently healthy women in the menopause transition (40-52 years), with menstrual function, who were experiencing minor menopausal symptoms, were selected from the general population by advertising. INTERVENTIONS: Active arm--oral conjugated oestrogens (0.625 mg daily) and cyclic medroxyprogesterone acetate (10 mg daily) on Day 14-27 of each menstrual cycle; placebo arm--placebos of both medications. MAIN OUTCOME MEASURES: Excess change from baseline associated with active compared with placebo treatment for all variables; effect of order of treatment. RESULTS: Baseline biochemical values were similar for both treatment-order groups, but baseline blood pressures and body weights were higher in the group receiving placebo first. With treatment, there were no differences in overall values for body weight and blood pressure (P > 0.4), and order of treatment had no significant influence (P > 0.3). There were no differences in total and low density lipoprotein cholesterol levels, overall or with order of treatment. Active treatment increased high density lipoprotein (HDL) cholesterol levels (overall and when placebo was given first; P = 0.001), and triglyceride levels (when active treatment was given first; P = 0.03). There was no overall treatment effect, but a significant order-of-treatment effect, on antithrombin III activity (mean levels were decreased by active treatment to a greater extent when it was given first; P = 0.02). The endometrium showed only physiological changes regardless of treatment. CONCLUSIONS: The lack of significant excess change in anthropometry, lipoprotein levels, antithrombin III activity, and endometrial histology in women given hormone treatment compared with placebo is reassuring. The increase in HDL cholesterol level is an extra benefit. Our study provides conclusive evidence that hormone treatment does not produce weight gain in women during the menopause transition.

Sorption of fluoroacetate (compound 1080) by Colestipol, activated charcoal and anion-exchange in resins in vitro and gastrointestinal decontamination in rats.

The sorption of sodium fluoroacetate (FA) by activated charcoal (AC) and 5 anion exchange resins (AERs) was tested in 2 simulated gastrointestinal (GI) fluids. Each sorbent was incubated with FA in a shaker-water-bath at 37 C for 24 h. Supernatant was removed and filtered, and the concentration of FA was determined by gas chromatographic detection of the dichloroaniline derivative. Under simulated gastric conditions (0.1 M HCl at approximately pH 1.5), the sorbents removed the following proportions of FA from solution: Carbosorb AC, 87 +/- 2%; cholestyramine, 28 +/- 7%; colestipol, 96 +/- 0%; Amberlite IRA-96, 70 +/- 2%; DEAE-Sephadex, 7 +/- 4%; Chitosan, 66 +/- 2%. Under simulated intestinal conditions (0.05 M sodium phosphate at approximately pH 7.4), binding was as follows: Carbosorb AC, 68 +/- 4%; cholestyramine, 53 +/- 5%; colestipol, 46 +/- 2%; AmberliteIRA-96, 10 +/- 20%; DEAE-Sephadex, 64 +/- 7%; Chitosan, 5 +/- 2%. All findings differed significantly from control, with the exception of Amberlite IRA-96 and Chitosan in phosphate buffer, and DEAE-Sephadex in HCI. In a second study, rats were given 5 mg FA/kg, and then gavaged with 2 g/kg Carbosorb AC, colestipol or bentonite. Over 4 h, the area under the curve of serum FA versus time (AUC) decreased by 39% in the rats treated with colestipol and 42% in those treated with bentonite. In contrast, Carbosorb AC did not affect the AUC,yet increased Tmax In another study, mortality was assessed 96 h after rats were orally dosed with 5 mg FA/kg followed by gavage with 2 g/kg Carbosorb AC, colestipol or water immediatey or 30 min after dosing. When the sorbents were given immediately, mortality was the same as control (75%). Surprisingiy, the 30-min delay resulted in lower mortality in colestipol-treated rats, (approximately 38%) compared to 100% in the group treated with Carbosorb AC. Before any recommendation can be made regarding the use of colestipol as a GI decontaminant, the latter findings require confirmation in an intensive care setting. The potential for synergistic effects with 2 or more sorbents also warrant investigating.

Fluoroacetate content of some species of the toxic Australian plant genus, Gastrolobium, and its environmental persistence.

Gas chromatography confirmed the relatively high concentrations of fluoroacetate found in toxic Gastrolobiums, a genus of indigenous Australian plants. Fluoroacetate concentration in these plants ranged from 0.1 to 3875 micrograms/g (ppm) dry weight, with young leaves and flowers containing the highest concentrations. However, there was considerable intrastand variation between individual plants of at least two species with coefficients of variation ranging from 94% to 129%. Despite the high concentrations of fluoroacetate in many species, only one of nine soil samples collected from beneath these plants contained fluoroacetate. None of the 16 water samples collected from nearby streams and catchment dams contained fluoroacetate. This suggests that fluoroacetate does not persist in this environment. Fluoroacetate was also found in the genus Nemcia, and very low levels of fluoroacetate (ng/g) were detected in the foodstuffs, tea and guar gum. The latter indicates that other plant species may produce biologically insignificant amounts of fluoroacetate.

Reduced expression of retinoblastoma gene product (pRB) and high expression of p53 are associated with poor prognosis in ovarian cancer.

Paraffin sections (n = 168, 27 benign, 16 low malignant potential [LMP] and 125 malignant tumours) from epithelial ovarian tumours were evaluated immunohistochemically for expression of retinoblastoma gene product (pRB) and p53 protein, and the relationship among pRB, p53 and cyclin-dependent kinase inhibitor 2 (CDKN2) gene product p16INK4A (p16) was analysed, following our previous study of p16. Forty-one percent of the benign, 50% of the LMP and most (71%) of the malignant tumours showed high pRB expression. High expression of pRB (>50% pRB-positive cells) significantly correlated with non-mucinous histological subtypes. Reduced pRB expression, substage and residual disease were significant predictors for poor prognosis in stage I patients. All the benign and most of the LMP (81%) tumours were in either the p53-negative or low p53-positive category, but nearly half of the malignant tumours had high p53 expression. High p53 accumulation was found in non-mucinous, high grade and late stage tumours. For well-differentiated carcinomas, high p53 expression was a predictor of poor prognosis. However, even though high p53 expression was not associated with histological subtype, stage or the presence of residual disease, high p53 expression was not an independent predictor when all clinical parameters were combined. For all ovarian cancers, a close correlation was found between high p53 and high p16 expression. The relationship between the expression of pRB and p16 depended on tumour stage. In stage I tumours, high pRB was associated with low p16 reactivity. On the other hand, most advanced tumours showed both high pRB and high p16 reactivity.