Biomedical subjects

J Järnberg

Publications and source records attributed to J Järnberg.

11 recordsLinked to original sources

PubMed1999

Physiologically based modeling of 1,2,4-trimethylbenzene inhalation toxicokinetics.

A physiologically based toxicokinetic model was developed for inhalation exposure of 1,2,4-trimethylbenzene (TMB) in man. The model consists of six compartments for TMB and one compartment for the metabolite 3,4-dimethylhippuric acid (DMHA). Based on previous experimental findings from human exposures to TMB, liver metabolism was divided in two pathways, one of the first order and one of the Michaelis-Menten type. Muscle tissue was split in two compartments to account for working and resting muscle tissues during bicycle exercise. The model was used to investigate how various factors influence potential biomarkers of exposure, i.e., TMB in blood and exhaled air and DMHA in urine. Increasing the work load from rest to moderate exercise (100 W) more than doubled all biomarker levels end of shift. The effect on next morning levels was even more pronounced, illustrated by a fivefold increase in the DMHA excretion rate. Simulations of five daily 8-h exposures suggest that biomarker levels end of shift remain fairly constant whereas the levels prior to shift increase gradually during the week. This suggests that end of shift levels reflect the exposure of the same day whereas levels Friday morning reflect exposure during the entire working week. Simulations with randomly generated exposures show that the variability due to fluctuating exposure is lower next morning than end of shift. End of shift exhalation rate of TMB is more sensitive to fluctuation than TMB in venous blood and DMHA in urine. Biomarker levels for 25 ppm exposure at different sampling times are given.

Administration, Inhalation↗

PubMed1998

Outcome of patients operated on for esophageal atresia: 30 years' experience.

PURPOSE: The aim of this study was to evaluate the outcome and late sequelae of patients with esophageal atresia or tracheoesophageal fistula. METHODS: Sixty patients with esophageal atresia or tracheoesophageal fistula (EA-TEF) were treated in Tampere University Hospital in the years 1963 through 1993. Long-term outcome was evaluated with a questionnaire, pulmonary and esophageal function test results, 24-hour pH level monitoring, tracheobronchoscopy findings, and esophagogastroscopy with biopsy sections and samples for bacterial cultures. RESULTS: One third of the respondents reported having impaired quality of life because of respiratory infections, dyspnea, and difficulties in swallowing and coughing at night. Eighteen percent had gastroesophageal reflux (GER) symptoms. The rate of symptoms decreased with age. Impaired pulmonary function, GER, abnormal esophageal peristalsis, and transit time were registered. Tracheobronchoscopy showed tracheal narrowing and inflammation in one third; in histopathologic analysis, however, the rate of inflammation was more than doubled. Histologically, esophageal inflammation was found in 51%, Barrett's esophagus in 6%, and a Helicobacter pylori infection in 21% of cases. The severity of GER, esophageal peristaltic abnormality, tracheal inflammation, and impairment of pulmonary function seems to be alleviated with age. CONCLUSIONS: Although the long-term outcome of EA-TEF patients seems to be favorable, respiratory and gastrointestinal symptoms as well as functional abnormalities remain frequent. Gastric metaplasia in the esophagus and the high rate of tracheal, esophageal, and gastric inflammation indicate a need for long-term follow-up.

Adolescent↗

PubMed1998

Long-term functional sequelae after paediatric burns.

Ninety-one patients with at least 5 per cent (median 10 per cent, maximum 50 per cent) total body surface area (TBSA) burns were clinically re-examined on average 17.3 yr after primary injury. The patients had sustained mostly superficial dermal scalds. The most common long-term functional sequelae were impaired tanning (n = 67; 77.7 per cent), diminished tactile sensibility (n = 50; 56.2 per cent) and increased reddening (n = 14; 15.6 per cent) either in the sun or the Finnish sauna. Five patients (6.3 per cent) had limited joint mobility and one patient experienced constrictive scars on her trunk during pregnancy. Scar appearance was significantly associated with impaired tactile sense (chi 2 = 11.87, DF = 2, p < 0.01; Spearman's R = 0.27, p = 0.03). Surprisingly, better scar appearance showed more disturbed touch sensation. The primary operative treatment (early excision and split skin grafting) was not associated with diminished sense of touch (chi 2 = 1.24, DF = 1, p = 0.27). Neither were scar appearance and poor tanning significantly associated (chi 2 = 1.63, DF = 1, p = 0.4). Only three patients suffered no functional detriments. In this series the harmful functional consequences were generally slight. The aetiological background (scalds) and the relatively small, superficially burned skin area probably explains the good late outcome. However, since nearly every burn-injured child will have some signs of the injury in adulthood, children present a constant challenge in the effort for better burn care and prevention.

Abdominal Injuries↗

PubMed1997

Inhalation toxicokinetics of 1,2,4-trimethylbenzene in volunteers: comparison between exposure to white spirit and 1,2,4-trimethylbenzene alone.

The objective of this study was to compare the toxicokinetics of inhaled 1,2,4-trimethylbenzene (1,2,4-TMB) in man after exposure to white spirit with that observed after exposure to 1,2,4-TMB alone. TMBs occur mainly in petroleum products and the TMBs or their metabolites have been suggested as suitable biomarkers of exposure to white spirit and other distillation products. The toxicokinetics were studied in 9 male, healthy volunteers exposed to solvent vapours in an exposure chamber for 2 h during a work load of 50 W. The subjects were exposed to 11 mg/m3 of 1,2,4-TMB on two occasions; during exposure to 1,2,4-TMB vapour alone and during exposure to 300 mg/m3 of white spirit. The 1,2,4-TMB isomer was analyzed in blood and exhaled air by gas chromatography. In addition, a major urinary metabolite of 1,2,4-TMB, 3,4-dimethylhippuric acid (3,4-DMHA), was analyzed by high performance liquid chromatography. Further the occurrence of acute effects was studied by means of a questionnaire. Irritation and central nervous system symptoms were recorded by ratings on a 100-mm visual analogue scale. Blood levels of 1,2,4-TMB and excretion rates of 3,4-DMHA in urine were markedly elevated both during and after exposure to white spirit as compared to exposure to TMB alone. Thus, it appears that components in white spirit inhibit the metabolic elimination of 1,2,4-TMB. This should be considered in biological exposure monitoring as well as in risk assessment. No irritation or central nervous system effects were reported at these conditions.

Administration, Inhalation↗

PubMed1997

Determination of dimethylhippuric acid isomers in urine by high-performance liquid chromatography.

In order to analyse metabolites in urine after trimethylbenzene (TMB) exposure a method based on high-performance liquid chromatography (HPLC) for determination of the six dimethylhippuric acids (2,3-DMHA, 2,6-DMHA, 2,5-DMHA, 2,4-DMHA, 3,4-DMHA and 3,5-DMHA) in urine has been developed. In contrast to earlier published methods, the present method allows detection of all possible isomers of DMHA in a single analysis. The DMHAs were extracted from urine with dichloromethane. After evaporation, the residue was dissolved in mobile phase and analysed by a stepwise gradient HPLC system with ultraviolet (UV) detection at 225 nm. Mobile phase A (1.25% acetonitrile and 0.3% acetic acid in water) was used up to a retention time of 59.5 min and mobile phase B (5% acetonitrile in water containing 0.3% acetic acid) was used for completion of the analysis at approximately 90 min. The DMHA isomers were chromatographed on a reversed phase Radial-Pak C18 column (4 microns; 100 mm x 5 mm inner diameter). The detection limit for the six isomers was 1.5 micrograms/ml (range 0.5-3.4, 100 microliters injection volume). The precision of the method was 4.2% relative standard deviation (range 3.8-4.4; 100 micrograms/ml). Standard curves of the DMHAs were linear over the interval 10-500 micrograms/ml in human urine. Individual DMHAs or the sum of DMHA isomers may be used as biological indicators of occupational exposure to TMBs.

Benzene Derivatives↗

PubMed1997

Urinary excretion of dimethylhippuric acids in humans after exposure to trimethylbenzenes.

The aim of this study was to determine the urinary excretion of dimethylhippuric acids (DMHAs) in humans after experimental chamber exposure to trimethylbenzene (TMB) vapor. The DMHAs have been put forward as suitable biomarkers of exposure to products containing TMBs such as white spirit and petrol. Ten healthy male volunteers were exposed to TMB vapor in an exposure chamber for 2 h at a work load of 50 W. The subjects were exposed on four occasions, to 25 ppm of 1,2,4-TMB, 1,2,3-TMB, and 1,3,5-TMB, respectively, and 2 ppm of 1,2,4-TMB. Urine was collected from the onset of exposure until the following morning. All six possible DMHA isomers were analyzed by high-performance liquid chromatography. About 22% of the inhaled amount of 1,2,4-TMB was excreted as DMHAs within 24 h, mainly as 3,4-DMHA. The 24-h recovery of 1,2,3-TMB as DMHAs was 11%. Only 3% of the absorbed amount of 1,3,5-TMB was excreted as 3,5,-DMHA. The half-times of the different DMHA isomers ranged from 4 to 16 h. In addition to analysis of DMHAs, the excretion of unconjugated dimethylbenzoic acids in urine was estimated to account for approximately 3% of the dose of all TMBs. In conclusion, the urinary excretion of DMHA isomers may serve as a good indicator of TMB exposure. In this controlled short-term-exposure study the sum of excretion rate of several DMHA isomers reflected exposure more closely than did the excretion rate of any single DMHA.

Adult↗

PubMed1997

The late appearance of scars after burns in childhood.

The late appearance of scars in children who had been burned, mainly scalded (n = 82, 90%) were analysed retrospectively from patient records and by clinical reassessment. All 91 patients who were re-examined had primarily sustained a burn of at least 5% of their total body surface area (TBSA). Only five patients showed no visible scars. The median interval between primary injury and re-examination was 17.3 years (range 6.4-30 years). Less than half of the patients (n = 36, 40%) had distinct scars without hypertrophy. The remaining 55 (60%) had either hypertrophic or constrictive scars. The scars were mostly located on the trunk (29%) and looked mainly hypertrophic (30.2%). The mean area of scars varied from 0.47% (on the neck) to 3.73% (on the left lower limb). There was no significant association between the appearance of the scar and any given method of treatment. The late cosmetic results were better than anticipated.

Adolescent↗

PubMed1996

Toxicokinetics of inhaled trimethylbenzenes in man.

The objective of this study was to determine the uptake and disposition of inhaled trimethylbenzenes (TMBs) in man. The toxicokinetics were studied in 10 male, healthy volunteers exposed to TMB vapor in an exposure chamber for 2 hr during a work load of 50 W. The subjects were exposed on four occasions to 25 ppm of 1,2,4-TMB, 1,2,3-TMB, and 1,3,5-TMB, and to 2 ppm of 1,2,4-TMB. The TMB isomers were analyzed in blood, urine, and exhaled air by gas chromatography. The relative respiratory uptake was in the range 56-64%. The elimination of TMBs was moderate compared to other aromatic solvents, with a total blood clearance of 0.6-1.0 liter hr(-1) kg(-1). Large volumes of distribution (30-39 liters/kg) and long terminal half-lives of the TMBs in blood (78-120 hr) imply extensive accumulation in adipose tissue. Exhalation during and postexposure accounted for 20-37% of the absorbed amount, whereas the urinary excretion of unchanged TMBs was low (< or = 0.002%). The kinetics of 1,2,4-TMB seemed linear up to 25 ppm. In addition, the occurrence of symptoms of acute effects was studied by means of a questionnaire. The subjects rated the degree of irritation and central nervous system symptoms on a 100-mm visual analog scale. No discomfort was reported at these exposure conditions.

Administration, Inhalation↗

PubMed1993

Paediatric burns in central Finland between the 1960s and the 1980s.

This study comprised 359 paediatric burn-injury cases. The patients were collected from the 1960s, 1970s and 1980s, taking 4 years from each decade. These children were treated exclusively in the Paediatric Surgery Department in the University Hospital of Tampere, Finland. We were interested in the backgrounds and living environments of our patients as well as the children themselves. Special attention was paid to risk factors and methods for prevention. Scalds at home and in the sauna rooms constituted the largest groups of injuries. The number of hospitalized patients has slightly decreased during the past three decades, whereas the proportion of girls has increased. The mortality was very low (0.28 per cent), a single case. This study shows that 80 per cent of born injuries in children occurred under the age of 4 years and over 80 per cent of all burn injuries involved hot liquids; modern kitchen technology has not significantly reduced this factor. The epidemiological profile of paediatric burns changed from the 1960s to the 1980s less than expected.

Adolescent↗

PubMedDate not supplied

Toxicokinetics of 1,2,4-trimethylbenzene in humans exposed to vapours of white spirit: comparison with exposure to 1,2,4-trimethylbenzene alone.

This study compares the toxicokinetics of inhaled 1,2,4-trimethylbenzene (124TMB) in men exposed to white spirit with that previously observed in the same individuals exposed to 124TMB alone. The appropriateness of using dimethylhippuric acid (DMHA) metabolites of 124-, 123- and 135TMB in urine as biomarkers of exposure is also addressed and the kinetics of n-decane, n-undecane and 123TMB is investigated. The toxicokinetics of 124TMB was studied in nine male, healthy volunteers exposed to solvent vapours in an exposure chamber for 2 h during a work load of 50 W. The subjects were exposed to 2 ppm (11 mg/m3) of 124TM B during exposure to 300 mg/m3 of white spirit. The 124TMB isomer was analysed in blood, urine and exhaled air by gas chromatography. The DMHA metabolites of all three TMB isomers were analysed in urine by high-performance liquid chromatography. The results were compared with previously published exposures to 2 and 25 ppm (120 mg/m3) of 124TMB vapour alone. In addition, the occurrence of acute effects was studied by means of a questionnaire. Irritation and central nervous system (CNS) symptoms were recorded by ratings on a 100 mm visual analogue scale. Blood levels of 124TMB and excretion rates of 3,4-DMHA in urine were markedly elevated both during and after exposure to white spirit compared to the same exposure level of 124TMB alone. No irritation or CNS effects were reported in the questionnaire at any exposure condition. It appears that components in white spirit interfere with the metabolic elimination of 124TMB. This should be considered in biological exposure monitoring as well as in risk assessment.

Adult↗

PubMedDate not supplied

Liquid/air partition coefficients of the trimethylbenzenes.

Liquid/air partition coefficients (lambda) of the three isomers of trimethylbenzene (1,2,3-,1,2,4-, and 1,3,5-TMB) were determined in vitro using automated head space gas chromatography. The liquids used were water (physiological saline), fresh human blood, and olive oil. The lambda water/air were 1.23 (95% confidence interval 1.11-1.35) for 1,3,5-TMB, 1.61 (1.47-1.75) for 1,2,4-TMB, and 2.73 (2.54-2.92) for 1,2,3-TMB. Corresponding lambda blood/air were 43.0 (40.8-45.2), 59.1 (56.9-61.3), and 66.5 (63.7-69.3). As expected, the TMBs have a high affinity for olive oil, the lambda oil/air being 9,880 (9,620-10,140), 10,200 (9,900-10,400), and 10,900 (10,500-11,300), respectively. It is notable that all partition coefficients increase in the order 1,3,5-TMB < 1,2,4-TMB < 1,2,3-TMB.

Air↗