Early Adverse Effects Research Articles

Identification of Stage-Specific Changes in Protein Secretion by Isolated Seminiferous Tubules from the Rat Following Exposure to Either m-Dinitrobenzene or Nitrobenzene

Identification of Early Stage-Specific Changes in Protein Secretion by Isolated Rat Seminiferous Tubules Following Exposure to Either m -Dinitrobenzene or Nitrobenzene. McLaren, T. T., Foster, P. M. D., and Sharpe, R. M. (1993). Fundam. Appl. Toxicol. 21, 384-392.The objective of this study was to identify effects of two known Sertoli cell toxicants on the secretion of proteins by seminiferous tubules (ST) isolated from adult rats at different stages of the spermatogenic cycle and cultured in vitro for 24 hr with [35S]methionine. Adult rats received a single oral dose of 50 mg/kg metadinitrobenzene (m-DNB) or 300 mg/kg nitrobenzene (NB). Long lengths of ST at stages II-V, VI-VIII or IX-XII were then isolated from control and treated rats at 1 or 3 days post-treatment; selection of stages was based on the stage specificity of the early (24-72 hr) adverse effects of m-DNB and NB on spermatogenesis in vivo. In addition, ST at the same stages were isolated from untreated rats and cultured in the presence or absence of m-DNB or NB (10-4 M). Incorporation of [35S]methionine into secreted proteins was assessed and the pattern of protein secretion evaluated using two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (2-D SDS-PAGE). ST isolated from rats pretreated 24 hr earlier with NB in vivo showed a significant decrease in the overall incorporation of [35S]methionine into secreted proteins at stages VI-VIII and IX-XII, whereas ST at stages II-V showed no such change; comparable protein changes were observed when 10-4 M NB was added in vitro for 24 hr to ST isolated at the same stages from untreated rats. Similar results were obtained when ST protein secretion was evaluated 72 hr after treatment with NB in vivo or after the addition of NB in vitro to isolated ST from untreated rats for 24 or 72 hr. In general, the results obtained after exposure to m-DNB were comparable to those observed for NB, with the exception that the incorporation of [35S]methionine into secreted proteins by ST at stages II-V tended to be increased by m-DNB exposure. Analysis of ST-secreted proteins by 2-D SDS-PAGE identified 6 "marker proteins" (IMP) which showed major reproducible changes in secretion following exposure to either in DNB or NB. In most cases (MP-1, -2, -3, -5, and -6) their secretion was reduced markedly; two of these proteins (MP-2 and MP-3) are secreted almost exclusively at stages VI-VIII and correspond in molecular size and pI to two recently reported androgen-regulated proteins which are thought to be products of the Sertoli cell. Exposure to either NB or m-DNB also resulted in the appearance of one protein (MP-4) which was not secreted in detectable amounts by ST from control animals. Previous data has shown that by 24 hr after administration of either m-DNB or NB to rats there is massive loss/degeneration of pachytene spermatocytes at stages VI-XII, whereas stages II-V of the spermatogenic cycle are not affected until 72 hr. The presently observed protein changes therefore either precede (stages II-V) or accompany (stages VI-XII) germ cell degeneration. This suggests that they may have potential use as markers of early toxicant-induced damage and/or that changes in these proteins may mediate some of the adverse testicular effects of m-DNB and NB.

Morbidity among municipal waste incinerator workers

Objective: The present study investigated the olfactory function in workers exposed to moderate airborne cadmium (Cd) levels, with the purpose of identifying possible early adverse effects of the metal, not demonstrable with the traditional diagnostic methods. Methods: The exposed group consisted of 33 men employed in cadmium fusion, sintering and alloys lamination. Two reference groups were considered: the first consisted of 39 subjects assigned to manual workings, but not exposed to harmful substances for olfaction (drivers, warehousemen); the second was characterized by 23 subjects exposed to iron and steel welding fumes (iron base alloys), non-specific irritants on the respiratory tract. Olfactory threshold and odor identification ability were separately quantified. Individual occupational exposure was studied by calculating the mean blood and urinary cadmium values (CdB and CdU, respectively) of the five years period during which, for each worker, the highest levels of dose indicators were measured. As indicator of renal tubular damage, urinary β2-microglobulin levels in the same quinquennium were monitored. Results: Mean olfactory threshold scored significantly higher in Cd workers (−5.26 log10 v/v, P=0.02) than did in controls (welders: −5.78 log10 v/v; P=0.26 compared to non-exposed −6.37 log10 v/v). The odor identification test findings for Cd workers were similar to those of the reference groups. Moderate blood and urine cadmium levels (mean CdB 3.7 μg/l; mean CdU 4.4 μg/g creatinine) accompanied threshold impairment. Olfactory threshold weakening was confirmed in the subgroup of Cd workers in which urinary β2-microglobulin never exceeded 300 μg/l (−5.41 log10 v/v; P=0.045 compared to non-exposed). Conclusions: These data suggested that possible early toxic effects of the metal can occur at low levels, close to the limits proposed by the American Conference of Governmental Industrial Hygienists (ACGIH®), confirming the hypothesis that primary olfactory neuron may represent the early target for cadmium toxic action. The action of the metal seemed to be due to an elective tropism for the olfactory epithelium and not to a non-specific irritant effect on the nasal cavity. The mechanism of this effect did not appear linearly dose-related. These findings underline the importance of olfactory tests to identify the early effects of xenobiotics even at low-exposure levels, and to contribute to verify the adequacy of the current exposure limits.

Smoking and blood pressure in the leg

To determine whether the calf:brachial ratio for systolic blood pressure is reduced in both current and ex-smokers of cigarettes. Cross-sectional study of the calf:brachial systolic blood pressure ratio and smoking history. Four hundred and ten male and 138 female civil servants aged 35-59 years working in the Department of the Environment Building, London. In men the systolic blood pressure ratio (Doppler calf:auscultatory brachial) decreased above the age of 50 years. However, different patterns were observed in those who had smoked at some time and those who had never smoked. In those who had never smoked the ratio in men aged 35-44 years was lower than that in men aged 55-59 years. In those who had smoked the average ratio rose from the age of 35-44 years to the age of 45-49 years and then fell to below the former value at the age of 55-59 years. There was a significant difference between lifelong non-smokers and current smokers at age 55-59 years. The pattern was similar in both male ex- and current smokers, and ex-smokers had results intermediate between those for current smokers and those who had never smoked. In women who had never smoked the ratio increased from the age of 35-44 years to the age of 50-59 years. In women aged 50-59 who currently smoke or used to smoke cigarettes the average ratio was close to that for women aged 35-44 years who had never smoked. The calf:brachial systolic blood pressure ratio is a simple measurement that may prove useful in detecting the early adverse effects of smoking on peripheral vascular disease. Lower ratios at older ages occurred in both current and ex-smokers, and the effects of smoking on peripheral arterial disease may not be easily reversible at older ages.

Effects of inhaled budesonide on serum markers of bone metabolism in children with asthma

The effects of inhaled glucocorticoids on serum markers of bone formation were evaluated in asthmatic children. Serum total alkaline phosphatase (AP), bone alkaline phosphatase (BAP), osteocalcin, and the novel marker of bone formation, carboxypropeptide of type I procollagen (PICP), were measured. In the cross-sectional part, long-term glucocorticoid users were compared with sodium cromoglycate (SCG) users. In the boys ( n = 16), but not in the girls ( n = 11), PICP was significantly lower in the glucocorticoid users than in the SCG users. PICP correlated positively with BAP ( n = 54; groups combined, r = 0.29, p < 0.05). I the longitudinal part, the effects of inhaled budesonide or SCG, both used for the first time, were evaluated before and after 1 and 5 months of treatment. The budesonide dose was 800 μg/m 2/day for 1 month and thereafter half of that. The SCG dose was 30 mg/day throughout the study. Only during budesonide use did osteocalcin and PICP decrease, the median osteocalcin by 8% at 1 month ( p < 0.05) and by 6% at 5 months ( n = 15), and PICP by 5% at 1 month ( p < 0.05) and by 28% at 5 months ( n = 7, p < 0.07). AP and BAP did not change significantly. Decreased PICP suggests decreased bone formation rate. PICP might be clinically useful as a marker of early adverse effects of glucocorticoids on bone.

Responses of Turkey Poults to Virginiamycin as Influenced by Litter Condition and Experimentally Induced Stunting Syndrome

Two experiments were conducted to evaluate the effect of virginiamycin (VM, 22 mg/kg of diet) on performance of uninfected (CON) turkey poults and those infected (INO) with stunting syndrome and reared on used woodshavings (Experiment 1) or on clean or used woodshavings (Experiment 2). Virginiamycin improved BW (P<.001) and feed efficiency (FE) (P<.05) from 1 to 29 days of age, irrespective of type of litter or disease condition. The increase in BW induced by VM, however, was greatest when poults were kept on used litter, resulting in significant (P<.05) VM by litter interaction. Induced stunting syndrome depressed BW (P<.01) to 29 days of age and impaired FE from 1 to 9 days of age (P<.05) and from 5 to 9 days of age (P<.01) in Experiments 1 and 2, respectively. Virginiamycin did not prevent early adverse effects of INO on BW and FE, but facilitated notable recovery of INO poults relative to INO poults not fed VM. Virginiamycin increased specific activities of maltase and sucrase of the jejunum of CON poults in Experiments 1 and 2; in Experiment 2, this VM effect was evident irrespective of type of litter. Maltase-specific activity and sucrase were reduced by INO (P≤.05 and P≤.01 in Experiments 1 and 2, respectively) and VM did not modify this effect. The maltase and sucrase data suggest that VM improved BW and FE of CON poults, in part, by helping to maintain digestive and absorptive functions of the small intestine during the early growth period, but, in the instance of INO poults, VM was not effective in this regard.

THE EFFECT OF INDOMETHACIN ON THE FEBRILE RESPONSE FOLLOWING OKT3 THERAPY1

Fifty renal transplant recipients with histologically documented acute allograft rejection were treated with OKT3 monoclonal antibody therapy. Group 1 (n = 25) received standard premedication with steroids, acetaminophen, and diphenhydramine. Group 2 (n = 25) received these agents plus indomethacin in an attempt to minimize the early adverse effects associated with OKT3. At 1 hr prior to the first dose of OKT3, 50 mg of indomethacin was administered orally followed by 25 mg every 6 hr for the next 48 hr. Demographics were similar in the two groups. Reversal of rejection occurred in 23 of 25 (92%) in group 1, and in 22 of 25 (88%) in group 2. Graft survival rates at six months after the rejection were 88% in group 1 and 80% in group 2. There was a single patient death in group 2, due to a suicide in a patient with a functioning kidney and pancreas graft. The maximum temperature was significantly diminished in the group receiving indomethacin during the first three days of OKT3 therapy. The percentage of patients with a maximum temperature less than 100 degrees F was significantly higher in group 2: day 1--16% vs. 36%, day 2--12% vs. 48%, day 3--52% vs. 68% for group 1 and group 2, respectively. No serious side effects occurred in either group--however, subjective side effects were less common in group 2. Serum creatinine levels were similar in the two groups prior to rejection, at the start of OKT3 therapy, at the peak during OKT3 therapy, at the end of OKT3 therapy, and 30 days and 180 days post OKT3. The data indicate that the concurrent use of indomethacin with OKT3 appears to significantly decrease the initial febrile response without compromising renal function or the efficacy of OKT3 therapy.

Evaluation of changes in the secretion of immunoactive inhibin by adult rat seminiferous tubules in vitro as an indicator of early toxicant action on spermatogenesis

A method for culturing isolated seminiferous tubules (ST) from adult rats for 1–3 days has been developed and optimized rigorously on the basis of the secretion of immunoactive inhibin under basal conditions and after maximal stimulation with rat FSH or dibutyryl cyclic AMP. The effect on these cultures of three known testicular toxicants was assessed. Of these, two are though to act on the Sertoli cell, meta-dinitrobenzene (mDNB) and nitrobenzene (NB), while the third, methoxy acetic acid (MAA), is thought to act on pachytene spermatocytes. In addition, the effect of a possible testicular toxicant, 3-mononitrotoluene (3-MNT), was investigated. These data were compared with those obtained using cultures of immature rat Sertoli cells (SC) or SC + germ cells and with data on the effect of equivalent doses of the compounds on the secretion of immunoactive inhibin in vivo. In studies designed to optimize conditions for the secretion of immunoactive inhibin by ST in culture, significant effects were found of the type of culture medium used, the duration of culture, the total and individual length of tubules used, etc. All subsequent studies with toxicants utilized optimal conditions. Addition of either mDNB or NB to ST cultures at 10 −5 or 10 −3 m, or MAA at 10 −4 m, stimulated basal secretion of immunoactive inhibin by two- to fourfold on Days 1, 2, or 3 of culture while FSH or dibutyryl cyclic AMP-stimulated secretion of immunoactive inhibin was either unaffected or was enhanced to a small extent. At the same doses, mDNB or NB also enhanced secretion of immunoactive inhibin by SC cultures, although these effects were more variable and of smaller magnitude than the effects on ST cultures. In contrast, addition of up to 10 −3 m MAA to cocultures of SC + germ cells had no effect on the secretion of immunoactive inhibin. Exposure of rats in vivo to levels of mDNB, NB, or MAA similar to those which stimulated secretion of immunoactive inhibin in vitro resulted in a two- to fourfold increase in the levels of immunoactive inhibin in testicular interstitial fluid (IF) at 1 and 3 days post-treatment, and this was associated with early impairment of spermatogenesis (as judged by testis weight). In contrast to these effects, addition of 3-MNT to ST or SC cultures had no effect except at 10 −3 m, when the secretion of immunoactive inhibin was increased marginally. Treatment of rats with an equivalent dose of 3-MNT in vivo resulted in death, but exposure to the highest nonlethal dose (1 g/kg) had no significant effect either on spermatogenesis or on the levels of immunoactive inhibin in testicular IF. In view of these findings, it is concluded that modulation of the secretion of immunoactive inhibin by isolated ST from adult rats has considerable potential as an in vitro screening method for investigating potential adverse effects of chemicals on spermatogenesis, and thus merits more detailed evaluation. Moreover, because of the agreement between in vitro and in vivo findings, measurement of the levels of immunoactive inhibin levels in vivo in testicular IF (or blood) may also be useful in the detection of early adverse effects of chemicals on spermatogenesis.

Evaluation of Changes in the Secretion of Immunoactive Inhibin by Adult Rat Seminiferous Tubules in Vitro as an Indicator of Early Toxicant Action on Spermatogenesis

Evaluation of Changes in the Secretion of Immunoactive Inhibin by Adult Rat Seminiferous Tubules in Vitro as an Indicator of Early Toxicant Action on Spermatogenesis. Allenby, G., Foster, P. M. D., and Sharpe, R. M. (1991). Fundam. Appl. Toxicol16, 710–724. A method for culturing isolated seminiferous tubules (ST) from adult rats for 1–3 days has been developed and optimized rigorously on the basis of the secretion of immunoactive inhibin under basal conditions and after maximal stimulation with rat FSH or dibutyryl cyclic AMP. The effect on these cultures of three known testicular toxicants was assessed. Of these, two are thought to act on the Sertoli cell, meta-dinitrobenzene (mDNB) and nitrobenzene (NB), while the third, methoxy acetic acid (MAA), is thought to act on pachytene spermatocytes. In addition, the effect of a possible testicular toxicant, 3-mononitrotoluene (3-MNT), was investigated. These data were compared with those obtained using cultures of immature rat Sertoli cells (SC) or SC + germ cells and with data on the effect of equivalent doses of the compounds on the secretion of immunoactive inhibin in vivo. In studies designed to optimize conditions for the secretion of immunoactive inhibin by ST in culture, significant effects were found of the type of culture medium used, the duration of culture, the total and individual length of tubules used, etc. All subsequent studies with toxicants utilized optimal conditions. Addition of either mDNB or NB to ST cultures at 10−5 or 10−3 m, or MAA at 10−4 m, stimulated basal secretion of immunoactive inhibin by two- to fourfold on Days 1, 2, or 3 of culture while FSH or dibutyryl cyclic AMP-stimulated secretion of immunoactive inhibin was either unaffected or was enhanced to a small extent. At the same doses, mDNB or NB also enhanced secretion of immunoactive inhibin by SC cultures, although these effects were more variable and of smaller magnitude than the effects on ST cultures. In contrast, addition of up to 10−3 m MAA to cocultures of SC + germ cells had no effect on the secretion of immunoactive inhibin. Exposure of rats in vivo to levels of mDNB, NB, or MAA similar to those which stimulated secretion of immunoactive inhibin in vitro resulted in a two-to fourfold increase in the levels of immunoactive inhibin in testicular interstitial fluid (IF) at 1 and 3 days post-treatment, and this was associated with early impairment of spermatogenesis (as judged by testis weight). In contrast to these effects, addition of 3-MNT to ST or SC cultures had no effect except at 10−3 m, when the secretion of immunoactive inhibin was increased marginally. Treatment of rats with an equivalent dose of 3-MNT in vivo resulted in death, but exposure to the highest nonlethal dose (1 g/kg) had no significant effect either on spermatogenesis or on the levels of immunoactive inhibin in testicular IF. In view of these findings, it is concluded that modulation of the secretion of immunoactive inhibin by isolated ST from adult rats has considerable potential as an in vitro screening method for investigating potential adverse effects of chemicals on spermatogenesis, and thus merits more detailed evaluation. Moreover, because of the agreement between in vitro and in vivo findings, measurement of the levels of immunoactive inhibin levels in vivo in testicular IF (or blood) may also be useful in the detection of early adverse effects of chemicals on spermatogenesis.

The sonographic features and implications of fetal pleural effusions

Pleural fluid was detected by ultrasound in three fetuses as an anechoic area surrounding the echogenic fetal lung. In one fetus the underlying lung was small, immobile and of abnormal contour; death occurred in the neonatal period and the lung was found to be hypoplastic. In two other fetuses the lungs appeared sonographically normal, being mobile with normal contours. Both survived, one following spontaneous intra-uterine resolution of the effusion and the other after early neonatal intervention prompted by the antenatal diagnosis. Sonography can detect pleural fluid in utero and may permit differentiation between normal underlying lung and pulmonary hypoplasia. We recommend serial scanning to detect early adverse effects of pleural effusion upon the fetus and to plan management changes.

Aortic dissection: A six year experience with 117 patients

Acute aortic dissection is a medical emergency that demands immediate recognition and early precise angiographic diagnosis. One hundred seventeen patients were found to have aortic dissection between 1980 and 1986. Clinical presentation is of importance since hypertension favors the presence of type B dissection, whereas normotension or hypotension is usually indicative of a type A lesion. Supportive treatment should allow stabilization for diagnosis by angiography or computerized tomography in order to proceed with early surgical repair of all type A dissections. Management of the acute type B patient should initially be medical, but immediate surgical treatment should be carried out if there is failure to control the hypertension, continued pain, expansion or rupture of the aneurysm (including appearance of a pleural collection), development of a neurologic deficit, or evidence of compromise of a major infradiaphragmatic aortic branch. Any delay in surgical treatment once an indicative complication is identified will have an early adverse effect on prognosis. By applying these guidelines, an overall 65 to 75 percent hospital survival rate should be achieved.

Present status and trends in biological monitoring of exposure to industrial chemicals.

This paper describes the current practice of biological monitoring of populations exposed to occupational or environmental pollutants. The three types of monitoring are ambient monitoring, biological monitoring of exposure, and health surveillance (also called biological monitoring of effects). The trend in biological monitoring today is to develop tests that provide information on the amount of chemical bound to the critical sites of action (target dose). Ambient monitoring and biological monitoring assess the health risk by comparing the current exposure with the permissible exposure limits. They are essentially preventive activities. By contrast, health surveillance or biological monitoring of effects assesses the health status and aims at detecting the early adverse health effects. Health surveillance is part of the medical screening program for the early detection of health impairment due to industrial chemicals.

Effects of neonatal treatment with 6-aminonicotinamide on basal and isoproterenol-stimulated ornithine decarboxylase activity in cerebellum of the developing rat

6-Aminonicotinamide (6-AN) is a nicotinic acid (vitamin B 3) antagonist which, when administered to immature animals, has a profound influence on brain development. To explore the biochemical mechanisms which underlie these actions, we evaluated effects of 6-aminonicotinamide on ornithine decarboxylase, an enzyme involved in cellular replication and differentiation. The cerebellum of the neonatal rat was chosen for study because it represents a brain region which undergoes major maturational events postnatally. When given to neonatal rats, 6-aminonicotinamide (10 mg/kg, i.p., on days 1, 3, 5 and 7) caused a prompt and persistent inhibition of the enzyme well in advance of adverse effects on tissue weight or on general growth. In addition, the ability of the cerebellum to respond to trophic stimulation by a β-adrenergic agonist, isoproterenol, was attenuated markedly. Assessment of cerebellar morphology indicated an early adverse effect of 6-AN on granule cell division, resulting in eventual disruption of the characteristic laminar structure of this brain region. These data support the view that reduced ornithine decarboxylase activity and impairment of its reactivity to growth stimuli participate in the toxic effects of 6-aminonicotinamide on brain development.

Arsenic exposure to smelter workers. Clinical and neurophysiological studies.

Forty-seven copper smelter workers, exposed to airborne arsenic for 8-40 years, were examined clinically with electromyography, and the motor and sensory conduction velocities in their arms and legs were determined. Fifty age-matched industrial workers not exposed to arsenic formed a reference group. The level of arsenic in the air at the smeltery was estimated to be below 500 micrograms/m3 before 1975 and approximately 50 micrograms/m3 thereafter. Urine analyses of arsenic showed a mean value of 71 micrograms/l (1 mumol/l) in the exposed group; this value is lower than that found in earlier studies reporting clinically detectable neuropathy. Only minor neurological and electromyographic abnormalities were found. A slightly reduced nerve conduction velocity in two or more peripheral nerves was more common among the arsenic workers than the referents, and a statistically significant correlation between cumulative exposure to arsenic and reduced nerve conduction velocity in three peripheral motor nerves was found. This occurrence was interpreted as a sign of slight subclinical neuropathy. In conclusion the risk of clinically significant neuropathy is small when exposure is kept below 50 micrograms/m3 in workroom air. The subclinical findings may be of interest in relation to the prevention of early adverse health effects from arsenic exposure.

Effects of Comb Dubbing on the Performance of Laying Stocks

Three studies were conducted with birds dubbed at hatch vs. dubbed and dewattled at 118 days or 255 to 260 days of age or with normal hens. In the first, involving 5928 pullets of four strains housed 1 per cage, dubbing and dewattling at 255 to 260 days caused small adverse effects on egg numbers as compared with nondubbed controls. Body size was reduced, and both egg weight (EW) and shell strength were increased slightly. In the second study, involving 8180 pullets of nine strains housed 1 per cage, dubbing and dewattling at 118 days slightly increased survivor egg production (SEP) and laying house mortality, and reduced age at first egg, 240-day EW, and 450-day Haugh units (HU), as compared with dubbing only at hatch. There were significant strain by dubbing treatment interactions for hen-day rate of lay (HDR) and SEP. In the third study, involving 1824 pullets of three strain crosses housed 2 and 3 birds per cage (three different cage sizes), there were no significant differences between birds dubbed at hatch and those not dubbed. Variation in age at 50% production, SEP, and HDR was reduced for the dubbed groups. These studies show that the older the birds are when dubbed, the greater the negative effects of dubbing. Hens dubbed at hatch exhibit no effects with the early dubbing or adverse effects in the laying house.

Acute nifedipine withdrawal: Consequences of preoperative and late cessation of therapy in patients with prior unstable angina

Reports of acute ischemic events after withdrawal of calcium antagonist therapy in outpatients and during bypass surgery in patients with prior angina at rest prompted the examination of the effect of nifedipine withdrawal in 81 patients who had completed a prospective, double-blind randomized trial of nifedipine versus placebo for rest angina. Thirty-nine patients underwent bypass surgery for uncontrolled angina or left main coronary artery disease. No significant difference between patients withdrawn from nifedipine or placebo was seen in the incidence of perioperative myocardial infarction, hypotension requiring intraaortic balloon counterpulsation, vasopressor or vasodilator requirements or incidence of significant arrhythmias. An additional 42 patients had completed 2 years on a protocol consisting of nitrates and propranolol in addition to nifedipine or placebo. During a mean of 66 hours of continuous monitoring after withdrawal of nifedipine or placebo, heart rate and blood pressure were unchanged. A worsening of previously present angina at rest occurred in five patients who had continued to experience rest angina before drug withdrawal, four of whom were withdrawn from nifedipine. No patient with class I to III angina experienced new onset of rest angina during drug withdrawal. No patient experienced myocardial infarction. There was no significant difference between patients withdrawn from nifedipine or placebo in the duration or frequency of ischemic ST changes on continuous electrocardiographic monitoring, or in duration or positive results of serial exercise treadmill testing. Thus, no early adverse effects of acute nifedipine withdrawal were found in patients with prior rest angina at the time of bypass surgery or in stable patients receiving long-term medical therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Method of addition of bromocriptine to the drug regime of patients with advanced Parkinson's disease.

Using a method of a gradual increase of bromocriptine with a concomitant reduction of Sinemet (levodopa 250 mg + carbidopa 25 mg), 19 patients with advanced Parkinson's disease have been treated for periods of up to 22 months and 16 of them have shown improvements of varying degrees. Eighteen patients were able to tolerate bromocriptine addition, with early transient adverse effects occurring in seven cases. In contrast to several previously reported studies, it was found necessary to withdraw bromocriptine in only one case. With the drugs currently available, bromocriptine has a role in the management of patients with advanced Parkinson's disease. The method described here may allow a greater number of patients to be given a trial with this drug.

Noise Exposure and Prevalence of High Blood Pressure Among Weavers in Iran

821 weavers working in three textile mills were examined in this survey. It was found that 8.5% of the workers were hypertensive and 12.4% borderline. All these rates are significantly different from those of the control groups. Also there is a clear increase in the prevalence of hypertensive and borderline cases in the weavers in relation to the length of employment. These findings emphasize the need for, at least annually, periodic examination of the entire work population in order to detect early such adverse health effects and to consider suitable medical care.