Acute liver dysfunction among workers exposed to 2,2-dichloro-1,1,1-tryfluoroethane (HCFC-123): a case report.
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Biomedical subjects
Publications and source records attributed to T Takebayashi.
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Electrophysiologic experiments were done to identify the somatosensory afferent units in the shoulder and adjacent tissues of the rabbit. Conduction velocity and mechanical threshold of the units were examined to determine whether the units have a nociceptive function or proprioceptive function. Eighty mechanosensitive units were identified in the shoulder and adjacent tissues. Forty-six of these units were found in the rotator cuff area, 26 in the supraspinatus muscle, and eight in the infraspinatus muscle. These tissues contained low to high threshold Group II and Group III units. This study showed there are nociceptors that receive pain sensation and proprioceptors that receive position sense with motion of the shoulder in the rotator cuff and the supraspinatus and infraspinatus muscles. The high density of nociceptors found in the rotator cuff and infraspinatus muscles near their insertion to the shoulder suggests these tissues are more sensitive to noxious stimuli.
We examined with electrophysiological techniques the effects of experimentally induced inflammation on the mechanosensitive afferent units in the rotator cuff of the shoulder joint of 21 rabbits. We identified 21 mechanosensitive units belonging to group III. 12 units had mechanical thresholds of > 7.0 g and 9 units had thresholds of < 7.0 g. After injection of inflammatory agents, kaolin and carrageenan, into the joint space, ongoing afferent discharge rates increased in all units. The average discharge rate increased significantly from 7 imp/s to 15 imp/s after injection. 5 units had a decreased mechanical threshold after the injection. Acute inflammation seems to have an excitatory and sensitizing effect on the high- and low-threshold units in the rotator cuff.
OBJECTIVE: A prospective cohort study was designed to clarify the relations between occupational exposure to carbon disulphide (CS2) and its effects on arteriosclerosis in workers in 11 Japanese rayon manufacturing factories. This report is a cross sectional baseline observation in the first study year. METHODS: Study subjects were 432 male rayon workers (mean (range) age 35.5 (19.1-47.8); duration of exposure 13.4 (0.3-29.0)) and 402 male referent workers (age 35.8 (18.9-49.8)). Exposure to CS2 was assessed by determining the concentration of 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine. Mean (SD) TTCA was 3.42 (2.73) mg/g creatinine (Cr) (n = 422). About a quarter of the urine samples were > 5 mg/g Cr, a biological exposure index recommended by the American Conference of Governmental Industrial Hygienists. Health effects on arteriosclerosis were evaluated by measuring blood pressure, serum lipids, pulse wave velocity of the aorta, stiffness and blood flow of the carotid artery, and blood coagulation and fibrinolysis indices, and by use of brain magnetic resonance imaging, electrocardiogram (at rest and after exercise), ophthalmograph, and Rose's questionnaire. Information on potential confounding factors was collected by self administered questionnaire. RESULTS: Prevalence of microaneurysm of the retinal artery was significantly higher in workers exposed to CS2 (8.1%) than in referent workers (3.4%), and increased with age. Other examinations did not show any differences between the two groups even after allowance for confounding factors. CONCLUSIONS: Significant effects of CS2 on arteriosclerosis were not found in current rayon manufacturing workers, with the exception of induction of microaneurysm of the retinal artery.
OBJECTIVES: A prospective cohort study was initiated to clarify whether the current level of exposure to carbon disulphide (CS2) is low enough to prevent occurrence of subclinical health impairments or to ameliorate health effects due to past high exposure. This paper describes the effects of exposure to CS2 on the nervous and endocrine systems, and the subjective symptoms in a baseline observation. METHODS: The effects were evaluated of CS2 on the median nerve conduction velocity, neurobehavioural and psychological tests, and subjective symptoms related to solvents in 432 male workers exposed to CS2 and 402 reference workers from 11 rayon factories in Japan. Adjustment was made for potential confounding factors such as age or alcohol drinking. Exposure to CS2 was either dichotomised or categorised into three groups by job type. RESULTS: Reductions were observed in motor (-1.9 m/s) and sensory (-0.91 m/s for orthodromic and -1.1 m/s for antidromic) nerve conduction velocities in the workers exposed to CS2 at the spinning and refining processes. Small but significant increases were found in self rated depression scale score and decrease in digit span (backward) in the workers exposed to CS2. Of 54 subjective symptoms many were increased--namely, heavy feeling in the head, light headedness, fainting after suddenly standing up, tremor, dullness, and increased sensitivity of skin in the extremities, reduced grasping power, reduced sexual desire, and increased rough skin. The endocrinological indicator--the concentration of glycosylated haemoglobin--was also increased in the workers exposed to CS2. CONCLUSIONS: Subclinical effects on the nervous system and on glucose metabolism were found in the workers exposed to CS2. One interpretation is that relatively higher exposure to CS2 in the past may induce these, but the effects are still not entirely ameliorated under the current exposure to CS2. Another possibility is that the current exposure to CS2 may cause these positive findings. A follow up observation is necessary to clarify these questions.
Previous studies that used neonatal capsaicin (Cap) treatment to ablate C fibers indicate that C fibers act to inhibit lung damage and airway hyperresponsiveness after ozone (O3) exposure in rats. The purpose of this study was to determine 1) the role of tachykinins in these protective effects and 2) whether differences in minute ventilation (VE) during O3 exposure might account for the effect of Cap. In the first study, male Sprague-Dawley rats were exposed to 1 part/million O3 or air for 3 h. Four hours later, a bronchoalveolar lavage (BAL) was performed or airway responsiveness was measured. Rats were treated with CP-99994 and SR-48968, selective neurokinin-1- and -2-receptor antagonists, respectively, or with vehicle (Veh). O3 caused an increase in the number of neutrophils recovered from BAL fluid in both the Veh-treated and tachykinin-receptor antagonist (TKRA)-treated rats, but the number of neutrophils was approximately twofold greater in the TKRA-treated rats. In contrast, TKRA treatment had no effect on baseline pulmonary mechanics or airway responsiveness. After O3 exposure, the number of neutrophils in BAL fluid was also greater in Cap- than in Veh-treated rats. O3 reduced VE in both Veh- and Cap-treated rats, but the response was greater (reduction of 44.7 +/- 3.7 vs. 27.8 +/- 6.8%) and occurred earlier (10 vs. 70 min) in Cap- than in Veh-treated rats (P < 0.02). These results suggest that tachykinins mediate protective effects of C fibers against O3-induced lung inflammation. The results also indicate that the more pronounced effect of O3 on BAL neutrophils in Cap-treated rats is not the result of a greater inhaled dose of O3 resulting from greater VE.
This investigation deals with patients of more than 15 years of age and family members of children younger than 12 years of age to evaluate the pre-operative interviews using information sheets. The information sheets describe the anesthetic management and complications in a simple style. Sixty% of the patients and 75% of the children's family felt anxiety about the anesthesia and/or the operation (P < 0.05). More than a half of the patients did not want to receive informations about the anesthetic management and the risk of anesthesia. On the other hand, 9% of children's family did not want to know informations about the risk (P < 0.05). More than 80% of patients read the information sheets after the pre-operative interviews and about a half of patients answered that their anxiety before the surgery decreased. In this investigation, the children's family wanted to have information about the anesthesia or the operation more than patients themselves. The pre-anesthetic interviews using information sheets is useful to give information about anesthesia and to relieve anxiety of the patients and the children's family.
We have studied the mechanosensitive afferent units in the lateral ligament of the ankle of the cat, with reference to the causes of lateral instability after injury, using electrophysiological recording from the lumbar dorsal rootlets. We identified 30 mechanosensitive units in the lateral ligament; 28 (93%) were located near the attachment to the fibula and calcaneus, which included both low-threshold group-II units and low- and high-threshold group-III units. Our results indicate that there are both proprioceptors and nociceptors in the lateral ligament of the cat ankle, and confirm that afferent fibres from the lateral ligament may contribute to the stability of the joint by regulation of position and movement.
A simple sampling and analytical method for monitoring carbon disulfide (CS2) vapor was investigated to assess exposure to low levels of CS2 in a viscose rayon factory. CS2 vapor was adsorbed on polymer beads (poly (2,6-diphenyl-p-phenylene oxide)) packed in a diffusive sampling tube. The sampling tube was heated at 180 degrees C for 7 min using a Daily Exposure Limit Test Apparatus, and thermally desorbed CS2 was measured by a stain tube for CS2. In laboratory experiments, the indicated CS2 levels measured by this method were highly correlated with calibrated CS2 concentrations (1-40 ppm), exposure duration (1-8 hr) and cumulative exposure levels. The CS2 values were stable up to 7 days after sampling when the diffusive tubes were stored at 4 degrees C and 20 degrees C. The effects of relative humidity, wind velocity and hydrogen sulfide on the measured values were negligible. In a field survey, 65 workers in a viscose rayon factory wore both the diffusive sampling tube and a commercially available 3M 3500 organic vapor monitor on their collar during their 8-hr work period. CS2 concentrations obtained by the two methods were comparable and the correlation coefficient was 0.931. This method proved to be useful in determining the concentrations of CS2 to which workers were exposed.
In order to clarify the effects of acetone (AC) exposure on health, a cross-sectional study was carried out in 110 male AC-exposed and 67 male nonexposed shift workers. The AC workers ranged in age from 18.7 to 56.8 years (mean: 37.6 years) and in length of AC exposure from 0.5 to 34.3 years (mean: 14.9 years). The nonexposed workers ranged in age from 20.7 to 57.5 years (mean: 41.9 years). AC exposure levels assessed by personal passive monitors and biological monitoring indices measured at the end of the workshift were 19.6-1018 ppm in the breathing zone (AC-E, mean: 364 ppm), 2.5-422 ppm in alveolar air (AC-A, mean: 97.3 ppm) 4-220 mg/l in blood (AC-B, mean 66.0 ppm), and 0.75-170 mg/l in urine (AC-U, mean: 37.8 mg/l). Symptoms at the end of the workshift with good exposure-response relationships were eye irritation, tearing, and acetone odor, and symptoms within the previous 6 months with good exposure-response relationships were heavy, vague, or faint feeling in the head, nausea, loss of weight, and slow healing of an external wound. In the 30-44 year age range, simple reaction time and digit span scores in a short computerized neuro-behavioral test battery were significantly lower in AC workers, but exposure-response relationships were not clear. Manifest Anxiety Scale scores, Self-rating Depression Scale scores, R-R interval variation on the ECG, hematological examinations, serum biochemistry examinations for liver function, and phagocytic activity of peripheral neutrophils did not show any AC-related differences between the two groups. In view of the reported findings, the current occupational exposure limit of 750 ppm recommended by many governmental and academic associations seems to be too high to prevent the health effects of AC observed in this study.
Using male ICR mice, the LC50 and acute and subacute inhalation toxicity of dichlorosilane (SiH2Cl2, DCS) and the fate of DCS released into the air were investigated. DCS resolved and minute particles including silicon and chloride were observed, when DCS was released into the air. Most particles were under 1 micron in diameter. The LC50 of DCS at 4-h exposure was 144 ppm (nominal concentration). In the acute inhalation study, ten mice in each group were exposed to 64 ppm (nominal concentration) DCS for 1, 2, 4 or 8 h. Body weight loss, wheezing and piloerection were observed in mice exposed for 2 h or more. Histopathologically, injury to the nasal mucosa and trachea were observed in all exposed mice. Mice exposed to 32 ppm (nominal concentration) DCS for 2 or 4 weeks also exhibited depression of body weight gain, wheezing and piloerection. Squamous metaplasia of the nasal mucosa and tracheal epithelium was observed in both 2- and 4-week exposure groups. Exposure to DCS was irritant or corrosive to the respiratory tract with both acute and subacute inhalation. Apart from silane (SiH4), toxic effects of DCS seem to be characterized by chloride compounds derived from DCS.
We administered argatroban, a selective thrombin inhibitor, as an anti-coagulant during and following vascular surgery. Activated coagulation time was controlled easily by its continuous intravenous infusion. No abnormal bleeding tendency and thrombus formation in graft and blood vessel were observed. The activity of thrombin was inhibited under the infusion of argatroban. We conclude that argatroban is effective for anti-coagulant therapy during and following vascular surgery.
To develop a proper protocol for biological exposure monitoring of acetone, we evaluated whether exposure to acetone on the previous day affects the biological monitoring value at the end of a work day. One hundred and ten male workers exposed to acetone in three acetate fiber manufacturing plants were monitored using a liquid passive sampler on two consecutive working days after 2 days without exposure. Urine samples were collected at the start of the workshift and the end of the shift on both days for each subject. For ten exposed workers urine samples were collected approximately every 2 h during and after the first working day until the following morning. Acetone concentrations in urine (Cu) at the start of the first working day were 1.3 +/- 2.4 (range: ND-14.1) mg/l in nonexposed workers and 2.4 +/- 5.6 (range: ND-40.3) mg/l in exposed workers. The urinary acetone concentration at the beginning of the second working day indicated that urinary levels of acetone do not decline to background level by the following morning when exposure concentration exceeds 300 ppm. However, linear regression analysis demonstrated that the relationship between environmental exposure level and urine level was similar on the 1st day and the 2nd day. Thus, although urine acetone levels did not return completely to baseline after high exposures, under the present exposure levels the exposure on the previous day did not significantly affect urinary acetone at the end of the workshift of the next day.
Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional growth factor that promotes proliferation, motility, and morphogenesis in epithelial cells. Recently the HGF receptor, c-met protooncogene product, has been shown to be expressed in developing limb buds (Sonnenberg, E., D. Meyer, M. Weidner, and C. Birchmeiyer, 1993. J. Cell Biol. 123: 223-235), suggesting that some populations of mesenchymal cells in limb buds respond to HGF/SF. To test the possibility that HGF/SF is involved in regulation of cartilage development, we isolated chondrocytes from knee joints and costal cartilages of 23-d embryonic and 4-wk-old rabbits, and analyzed the effects of HGF/SF on migration and proliferation of these cells. We found that HGF/SF stimulated migration of cultured articular chondrocytes but did not scatter limb mesenchymal fibroblasts or synovial fibroblasts in culture. HGF/SF also stimulated proliferation of chondrocytes; a maximum three-fold stimulation in DNA synthesis was observed at the concentration of 3 ng/ml of HGF/SF. Moreover, HGF/SF had the ability to enhance proteoglycan synthesis in chondrocytes. The responsiveness of chondrocytes to HGF/SF was also supported by the observation that they expressed the HGF/SF receptor. Addition of the neutralizing antibody to rat HGF/SF affected neither DNA synthesis nor proteoglycan synthesis in rat chondrocytes, suggesting a paracine mechanism of action of HGF/SF on these cells. In situ hybridization analysis showed that HGF/SF mRNA was restrictively expressed in the areas of future joint regions in developing limb buds and in the intercostal spaces of developing costal cartilages. These findings suggest that HGF/SF plays important roles in cartilage development through its multiple activities.
We investigated the effect of local injections of danazol suspension (DZS) into the uterine cervix. In the cervix, danazol (DZ) reached high concentrations 1 and 4-6 h after injection; then it decreased. In the endometrium, the DZ level reached a peak 1 h after injection, and then declined. On the other hand, the DZ concentration tended to increase with time after injection in ovarian tissue and it remained at a relatively constant level for more than 2 days. During treatment with DZS, various subjective symptoms and clinical findings gradually improved from the 4th week after the start of injection onward. Moreover, an improvement of subjective symptoms was observed in all the patients by the 24th week.
To determine safe exposure levels of tetraethoxysilane (TEOS) in the kidney, groups of male ICR mice (SPF grade) containing 10 animals each were exposed to TEOS, 100 ppm or 50 ppm, for 6 hours/day, 5 days/week, for 2 or 4 weeks. Tubulo-interstitial nephritis developed in mice exposed to 100 ppm for 2 and 4 weeks, but no kidney lesions or renal function changes were observed in mice exposed to 50 ppm. However, histopathological changes were detected in the nasal mucosa of mice exposed to 50 ppm TEOS. These results indicate that the occupational exposure level for TEOS should be strictly maintained below the current recommended exposure limit, 10 ppm, set by many countries and academic associations, and that renal tubular function of TEOS-exposed workers should be assessed and monitored for a long period.
In order to clarify the acute and subacute toxicity of diborane (B2H6, CAS: 19287-45-7) at low concentrations, male ICR mice were exposed to diborane for 1, 2, 4 or 8 h at concentrations of 1 or 5 ppm (phase I study), and for 6 h/day, 5 days/wk, over 2 or 4 wk at concentrations of 0.02 or 0.7 ppm (phase II study). Hematological and biochemical tests, and histopathological examinations of the cornea, nasal mucosa, respiratory tract and lung were carried out. All mice in both studies survived until they were sacrificed. In the phase I study, lung weight increased significantly in mice exposed to 5 ppm of diborane for 8 h. Histopathologically diffuse panbronchiolitis-like lesion was observed in mice exposed to 5 ppm of diborane for 2, 4 or 8 h. In the phase II study, slight infiltration of polymorphous neutrophil was observed mainly in the peribronchiolar region in mice exposed to 0.2 ppm or 0.7 ppm of diborane for 2 or 4 wk. In both studies, hematological and biochemical examinations failed to reveal any exposure-related changes. These results suggest that no-observed-effect level of diborane inhalation on the respiratory organs were 1 ppm in acute exposure, but 0.2 ppm of diborane inhalation for 2 or 4 wk seems to be unsafe.
In order to examine the toxicity of silane, male ICR mice were exposed to silane for 30 min (n = 8), 1 or 4 h (n = 12) at concentrations of 2500, 5000, 7500 (30-min experiment only) or 10,000 ppm. In the 1- and 4-h experiments, 12 mice were divided into two sub-groups: four for 2-day observation and eight for 2-week observation. The mortality was six deaths out of eight mice exposed to 10,000 ppm for 4 h. No deaths occurred in any of the other experiments. In the mice sacrificed 2 days after the exposure, acute renal tubular necrosis was observed at 10,000 ppm (1-h exposure) or at 2500 ppm or more (4-h exposure). Reduction in body weight, increase in relative kidney weight and blood urea nitrogen (BUN) level, and splenic atrophy and inflammatory changes of the nasal mucosa were also seen in the 10,000 ppm-4 h exposure group. In the mice sacrificed 2 weeks after the exposure, tubulo-interstitial nephritis (TIN) developed at 7500 ppm or more (30-min exposure) or at 5000 ppm or more (1- and 4-h exposure). BUN increased in a dose-dependent manner, and BUN in TIN positive mice was significantly higher than that in TIN negative mice (1- and 4-h exposure). No histopathological changes were observed in the glomeruli. These results indicate that the LC50 of silane in mice is between 5000 and 10,000 ppm for 4-h exposure and is greater than 10,000 ppm for 1-h or 30-min exposure.(ABSTRACT TRUNCATED AT 250 WORDS)