Low level saliva cotinine determination and its application as a biomarker for environmental tobacco smoke exposure.

1. The determination of personal exposures to environmental tobacco smoke (ETS) and respirable suspended particles (RSP) for housewives, and fixed site monitoring of their homes, have been undertaken by these authors throughout Europe, South East Asia and Australia. Median 24 h time weighted average (TWA) concentrations for ETS particles and nicotine were found to be significantly higher for housewives living in smoking households compared with those living in nonsmoking households. For Europe, median TWA concentrations of 4.1 and <0.26 microg/ml for ETS particles and 0.63 and < 0.08 microg/m3 for nicotine were found for housewives living in smoking and nonsmoking households respectively. 2. In addition to the measurement of RSP, ETS particles and nicotine, saliva cotinine concentrations were determined using a radioimmunoassay method with a limit of quantitation of 1 ng/ml. Median saliva cotinine concentrations of 1.4 and <1 ng/ml were determined for European housewives living in smoking and nonsmoking households respectively, which reflected the poor limit of quantitation of this methodology. A chromatographic method utilising tandem mass-spectrometric detection was developed and validated for the determination of both cotinine and 3-hydroxycotinine, two of the main metabolites of nicotine, with lower limits of quantitation of 0.05 and 0.10 ng/ml respectively. This method was applied to samples collected from subjects with a known ETS exposure history and median cotinine concentrations of <0.05 ng/ml for self-reported unexposed nonsmokers, 0.65 ng/ml for nonsmokers reporting some ETS exposure and 1.28 ng/ml for nonsmokers living with smokers were found. 3. In conclusion, the measurement of RSP and ETS concentrations derived from personal or fixed site monitors for housewives may provide some indication of potential exposures to dependent children. The recent development and application of a highly sensitive assay for the determination of cotinine in saliva has provided evidence to suggest that concentrations determined at sub-nanogram levels may be used as a biomarker for ETS exposure. This improved methodology, coupled with non-invasive sampling for saliva, may be of significance when considering the application of cotinine as a biomarker for ETS exposure in children.

Assessment of environmental tobacco smoke and respirable suspended particle exposures for nonsmokers in Prague using personal monitoring.

OBJECTIVE: Exposures to respirable suspended particles (RSP) and environmental tobacco smoke (ETS) were assessed in Prague, Czech Republic, to determine the range and degree of personal exposure by means of personal monitoring over a 24-h period. DESIGN: Self-reported nonsmokers were randomly selected from a representative sample of the population of Prague. Housewives were recruited into one group, primarily for assessment exposures in the home, and office workers were recruited into a second group for assessment of the contribution from the workplace. METHODS: A total of 238 randomly selected nonsmoking subjects collected air samples near their breathing zone by wearing personal monitors for 24 h. Samples collected were analyzed for RSP, nicotine, 3-ethenylpyridine, and ETS particles (using ultraviolet absorbance, fluorescence, and solanesol measurements). Saliva cotinine analyses were also undertaken to confirm the nonsmoking status of the subjects. RESULTS: The most highly exposed subjects in this study were office workers both living and working with smokers. Median time-weighted average exposure concentrations of 60 microg m(-3)RSP, 16 microg m(-3)ETS particles, and 1.6 microg m(-3) nicotine were determined for these subjects, who also had the highest median saliva cotinine level of 2.4 ng ml(-1). Housewives living in nonsmoking households were the least exposed subjects in this study, showing levels of 32 microg m(-3) RSP, 0.17 microg m(-3) ETS particles, and 0.15 microg m(-3) nicotine. As based upon median levels of ETS particles and nicotine, no group would potentially inhale or be exposed to more than 10 cigarette equivalents per year (CE/y) and the least exposed would inhale less than 1 CE/y. The most highly exposed (90th percentile levels) nonsmokers in this study, who both worked and lived with smokers, would potentially inhale up to 29 CE/y. Overall, the workplace was estimated to contribute between 45% and 49% of the annual exposure to nicotine and ETS particles, respectively. On the basis of determined saliva cotinine concentrations, a misclassification rate of between 1.7% and 2.5% was calculated. CONCLUSION: Highest exposures were apparent for office workers both working and living in smoking environments. and our findings suggest a significant contribution to overall ETS particle and nicotine levels from the workplace where smoking takes place. Overall, the rates at which subjects were determined to have misclassified their smoking status in this study were the lowest observed in any of the European cities investigated to date. Clearly, a more sensitive method of analysis for cotinine in body fluids is needed for more accurate determination of the levels expected for nonsmokers.

Measured exposures by personal monitoring for respirable suspended particles and environmental tobacco smoke of housewives and office workers resident in Bremen, Germany.

OBJECTIVE: Exposures to respirable suspended particles (RSP) and environmental tobacco smoke (ETS) were assessed in Bremen, Germany, as part of a European air quality study. The range and level of personal exposures were assessed for housewives and office workers. DESIGN: Nonsmokers were randomly selected from a representative sample of the population of Bremen. Housewives were recruited into one group primarily for assessment of exposures in the home and office workers, into a second group for assessment of the contribution of the workplace to overall exposure. METHODS: A total of 190 subjects collected air samples from areas close to their breathing zone by wearing personal monitors for 24 h. Samples collected were analysed for RSP, ultraviolet-absorbing particulate matter (UVPM), fluorescing particulate matter (FPM), solanesol-related particulate matter (SolPM), nicotine and 3-ethenylpyridine (3-EP). Saliva cotinine levels for all subjects were also established. RESULTS: Overall the levels found were quite low, with the majority of results being below the limit of quantification. Workers both living and working with smokers were exposed to the highest 24-h median quantities of RSP (789 micrograms) and ETS particles (128 micrograms) measured by FPM. The highest nicotine levels, based on median 24-h time-weighted average concentrations, were experienced by office workers working with smokers (0.69 microgram m-3). These workers were also found to have the highest median cotinine levels (1.6 ng ml-1). CONCLUSIONS: The most highly exposed workers, both living and working with smokers, would potentially inhale over 20 cigarette equivalents (CE) per annum as based on the upper decile levels. Housewives living with smokers could inhale up to 11 CE per annum as based on the upper decile levels. Locations outside the workplace, including the home, contribute most to overall RSP and ETS particle exposure. Consideration should be given to extending the personal monitoring period in cities where levels appear to be quite low.

Airway fluoroscopic diagnosis of vocal cord dysfunction syndrome.

BACKGROUND: Vocal cord dysfunction syndrome is often misdiagnosed as refractory asthma. Airway fluoroscopy has recently been proposed as an alternative to laryngoscopy in the initial evaluation of certain cases of suspected vocal cord dysfunction. OBJECTIVE: To evaluate the use of airway radiographs and fluoroscopy in a patient with suspected vocal cord dysfunction. METHODS: We used soft tissue technique airway radiographs and fluoroscopy to evaluate the glottic function during inspiration and expiration in a 9-year-old boy with refractory asthma and suspected vocal cord dysfunction. RESULTS: The study confirmed paradoxical vocal cord motion. CONCLUSIONS: Airway radiographs and fluoroscopy provide a rapid and noninvasive means of diagnosing vocal cord dysfunction. Patients should still have laryngoscopy performed at the earliest possible moment to rule out the possibility of other laryngeal abnormalities.

Assessment of air quality in Stockholm by personal monitoring of nonsmokers for respirable suspended particles and environmental tobacco smoke.

Exposure to respirable suspended particles (RSP) from all sources and environmental tobacco smoke (ETS) was assessed for 190 nonsmokers in Stockholm during 1994. Each subject wore a personal monitor for 24-h, provided saliva samples for cotinine analysis, and completed a detailed questionnaire about air quality and life-style. The subjects consisted of housewives and househusbands in one main group and working men and women in the second. The housewives and househusbands wore a single monitor throughout the 24-h period and the working subjects wore one monitor at work and a separate monitor while not at work. The geodemographic distribution of the recruited subjects accurately reflected the population of Stockholm. For most of the subjects, exposure to ETS and nicotine was at or below the limits of quantification (LOQ). This finding was supported by the fact that about 80% of the recruited subjects claimed that their exposure to ETS was "none" or "low". The concentration of RSP was found to be highest (median 39 micrograms.m-3) in homes where smoking occurred and below the LOQ in the workplace irrespective of its smoking status. These levels are at the lowest end of typical indoor air levels for RSP. For the housewives and househusbands living in smoking homes (nonsmoking homes in parentheses), the median exposure levels were 39 micrograms.m-3 (18 micrograms.m-3) for RSP, 17 micrograms . m-3 (0.12 micrograms . m-3) for ETS particles, and 1.1 micrograms.m-3 (0.05 micrograms.m-3) for nicotine. Both the pre- and postmonitoring continine saliva levels measured for these housewives and househusbands were 2.9 ng.ml-1 (pre-0.56 ng.ml-1, post-0.41 ng.ml-1). The highest exposure levels were recorded for the housewives and househusbands in the age range of 35-49 years. For the working subjects, the exposure measured in smoking workplaces (nonsmoking workplaces in parentheses) gave median levels of 16 micrograms.m-3 (16 micrograms.m-3) for RSP, 1.1 micrograms.m-3) for ETS particles and 0.2 micrograms.m-3 (0.15 microgram.m-3) for nicotine. Similarly measured exposures at home (nonsmoking homes in parentheses), including all other locations outside the workplace, gave median levels of 24 micrograms.m-3 (19 micrograms.m-3) for RSP, 1.4 micrograms. m-3 (0.2 microgram.m-3) for ETS particles, and 0.15 microgram.m-3 (0.07 microgram.m-3) for nicotine. Overall, the exposure levels of ETS due to living with smokers in Stockholm was found to be much lower than similar exposures measured previously in the United Kingdom and the United States. Over 70% of all the nicotine measurements and 60% of all the ETS measurements were below the LOQ. When the median values for nicotine and ETS particles are converted to cigarette equivalents, Stockholm housewives and househusbands living with smokers would receive 6-9 cigarette equivalents per year, working nonsmokers living with smokers would receive 0.6-0.7 cigarette equivalents at home, and nonsmokers working with smokers would be exposed to 0.1-0.2 cigarette equivalent at work. The exposures were therefore up to six times greater at home than in workplaces where smoking was occurring. Although all the subjects were recruited as nonsmokers on the basis of their self-reported nonsmoking status, saliva continine measurements were used for confirmation. Subjects with continine levels below 25 ng.ml-1 were considered to be nonsmokers although the selection of a threshold level within the range of 10-50 ng.ml-1 was not considered to be critical. With a threshold of 25 ng.ml-1, between 2.7% and 5.3% were later shown to be misclassified as nonsmokers, depending on the definition of misclassification used. During the study period the air quality in Stockholm could be described according a British nomenclature as "very good" for the majority of the time. The daily average at no time fell below "good," and the maximum hourly nitrogen dioxide level was 111 micrograms.m-3 (inner city at street level) on the coldest day

Citation analysis of 541 articles published in drug and alcohol journals: 1984-1988.

Citation histories of 541 articles published in 1984 in 12 drug and alcohol journals were followed through 1988. Considerable variability in mean citation rates across journals was observed. The mean citation rate for the 541 articles was 3.48. Approximately 71% of the articles examined were cited at least once between 1984 and 1988. The present findings suggest that articles published in drug and alcohol journals may be cited more frequently, and exert their influence longer, than those of the social science literature generally. Qualitative analyses suggest that methodological and review articles tend to be cited most frequently. The need for a comprehensive scientometric examination of the drug and alcohol literature is emphasized as is the potential role of multivariate techniques in the identification of variables predictive of individual article and journal citation rates.

Liver cirrhosis and biliary surgery: assessment of risk.

Operations on the biliary tract in cirrhotic patients are reported to have a higher than normal risk of operative morbidity and mortality. We reviewed 39 cases from two university-based hospitals over a five-year period. Each patient had biliary tract surgery and biopsy-proven cirrhosis. Eight patients died (21%), and major complications were found in 12 surviving patients (35%). Local and systemic sepsis was the major contributor, accounting for all of the deaths and 17 of the 22 (77%) complications among survivors. Choledochotomy was done in ten patients; three of them died (30%) and nine major complications occurred in the remaining five. Preoperative risk factors found to be predictive of this high morbidity and mortality were ascites (50% mortality, 50% morbidity), prolonged prothrombin time (29% mortality, 38% morbidity), and a serum albumin level of less than 3.5 mg/dl (33% mortality, 40% morbidity). The presence of other major systemic disease was not significantly different between survivors and nonsurvivors. In 12 patients with no ascites and normal preoperative serum chemistry values, no deaths and only one minor complication occurred. We conclude that although biliary surgery in cirrhotic patients carries a high mortality, this risk can be assessed preoperatively. There appears to be a small subgroup of patients with cirrhosis and cholelithiasis who can have a favorable outcome. Operative therapy in these patients should be reserved for the complications of the biliary tract.

Clarification of risk factors for abdominal operations in patients with hepatic cirrhosis.

Celiotomy in cirrhotic patients is reported to bear a high risk of operative morbidity and mortality. We reviewed 100 consecutive, cirrhotic patients who underwent nonshunt celiotomy. Thirty patients died and major complications occurred in another 30 patients. Hospital mortality rate was 21% in 39 biliary operations, 35% in 26 procedures for peptic ulcer disease, and 55% in nine colectomies . Fifty-two variables were compared between survivors without complication, survivors with complications, and nonsurvivors. A computer-generated, multivariant discriminant analysis yielded an equation predictive of survival. Utilizing coagulation parameters, presence of active infection, and serum albumin, the equation predicted survival with 89% accuracy. In a similar fashion, amount of operative transfusions, absence of postoperative ascites, pulmonary failure, gastrointestinal bleeding, and culture-positive urine predicted survival with 100% accuracy. We conclude that celiotomy in the cirrhotic patient is truly associated with very high morbidity and mortality, and preoperative assessment can predict survival with 89% accuracy.

Approaches to the management of shotgun injuries.

Shotgun wounds present specific challenges for the surgeon. Multiple penetrating wounds frequently involve large anatomic areas with potential multi-system injury. Experience with 121 patients sustaining shotgun wounds over the 5-year period ending 31 December 1981 was reviewed to assess results and evaluate treatment protocols. Sixty-six patients had chest wounds with pleural penetration. Twenty-four wounds were minor and were observed. Each had less than five pellets penetrating the pleura. Twenty-two patients had close-range injuries. Fourteen of these required chest tube drainage alone and eight patients required thoracotomy for control of bleeding. Eleven patients died, six as a direct result of the chest injury. In 55 patients with abdominal-retroperitoneal wounds exploratory operations were done if more than four pellets were thought to be lodged intraperitoneally or if signs of peritonitis were present, while lesser wounds without peritoneal findings were observed. In the 15 patients who did not have exploratory operations, there were no deaths or major complications. Thirty-five patients had exploratory operations. Two patients had five intraperitoneal missiles and no clinical evidence of peritonitis but were found to have significant intestinal perforations. Four patients died. Eighty-three patients with extremity wounds were classified according to location of injury. Forty-five had upper extremity wounds, with nine vascular injuries. Two patients died and one limb was amputated because of soft tissue infection. Thirty-eight patients had lower extremity wounds. Five had major vascular injuries. Preoperative arteriography was obtained in 13 patients with extremity injuries; the results of one of these were falsely negative. There were no deaths or amputations.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized blinded clinical trial of a rapid colonic lavage solution (Golytely) compared with standard preparation for colonoscopy and barium enema.

The efficacy and safety of the new colonic lavage solution, Golytely (an electrolyte-polyethylene glycol solution), was compared with standard 2- and 3-day bowel preparations in a randomized blinded study of patients undergoing colonoscopy and barium enema examination. Side effects, patient preference, and quality of examinations were monitored. Colonoscopy was scored by colonic segment for type of residual stool and percentage of bowel wall visualized. Barium enema was graded by stool particle size in the least clean segment. For colonoscopy, preparation with Golytely allowed better visualization of colonic mucosa (p less than 0.002) due to less retained stool (p less than 0.002), produced more optimal exams (p less than 0.002), and required less time to reach the cecum (p less than 0.05). Furthermore, it was preferred by patients, required less than 5 preparation time, and caused no notable side effects. For barium enema, no significant difference existed between preparations. We conclude that Golytely is effective for barium enema examination and is the preparation of choice for colonoscopy.

Iodine deficiency and brain development in the rat.

An assessment was made of the influence of low-iodine diet on somatic and brain development at birth (day 0) and 21 days postnatally in the rat. The rat mothers were proven to be iodine-deficient by assay of plasma thyroxine and thyroid stimulating hormone prior to mating, an at 21 days postnatally, when maternal thyroids were removed, weighed and stored for subsequent iodine analysis, along with those of the offspring. There were no significant differences in body weight or brain weight of the offspring at birth, or in the content of DNA or protein. However, at 21 days there was a significant reduction in body weight (21.7%) and whole brain weight (7.9%, P less than 0.2) which was associated with a significant fall n cholesterol content (12.4%, P less than 0.05) and protein level (9.6 %, P less than 0.01), while DNA was not significantly affected (6%). The greatest reduction in weight was seen in the cerebellum. The thyroids in these rats were double normal size, showed follicular cell hypertrophy and absence of colloid histologically, and contained 8% of the iodine content of controls. It is concluded that iodine deficiency retards both somatic and brain development, the change in the latter case being expressed as a reduction in cell size in the cerebral hemispheres and cerebellum, along with reduced myelination throughout the brain.

Low-iodine diet for producing iodine deficiency in rats.

A low-iodine diet has been prepared for rats, using locally available low-iodine ingredients. On analysis it has been shown to consistently contain 15-20 ng iodine/g. When fed to growing female rats, this diet produced severe iodine deficiency while not significantly affecting growth or reproduction. The deficiency was manifested by a fall in daily urinary iodine excretion (to less than 1 microgram/day) and a seven-fold increase in thyroid uptake (131I) observable within 3 months. Levels of plasma thyroxine (T4) and thyroid stimulating hormone (TSH) continued to change for 4-5 months, T4 falling from 69.9 to 7.5 nmol/l and TSH increasing seven-fold from a control value of 364 to 2406 ng/ml. Goitre was present in all iodine-deficient rats and iodine content in the thyroid was 10% of the control value.