Mixed solvent exposure and hearing impairment: an epidemiological study of 3284 men. The Copenhagen male study

Animal experiments and human studies have indicated an effecton auditory functions from exposure to organic solvents. Inthis study the relationship between self-assessed hearing problemsand occupational exposure to solvents was investigated in across-sectional design with 3284 participating men aged 53–74years. Exposure to solvents for five years or more resultedin an adjusted relative risk (RR) for hearing impairment of1.4 (95 per cent Cl: 1.1–1.9) in men without occupationalexposure to noise. Factors adjusted for were age, noise traumas,chronic middle ear infection and family history of hearing impairment.The prevalence of hearing impairment in men not exposed to organicsolvents was 24 per cent and the attributable risk from solventexposure was 9.6 per cent. Exposure for less than five yearshad no effect on hearing capacity. Occupational exposure tonoise for five years or more had an effect twice that of solvents,RR: 1.9 (95 per cent Cl: 1.7–2.1). In men exposed to bothsolvents and noise the effect of the latter dominated and noadditional effect from solvents was found. A subsample of 51men was examined with pure tone audiometry and 20 of 21 menwho reported abnormal hearing also fulfilled an audiometriccriterion for hearing impairment. In conclusion a damaging effecton hearing ability from long-term solvent exposure was foundin the present study. The relative effect was moderate but witha high background frequency of hearing problems in the unexposedsample the absolute effect, ie attributable risk, was considerableand of both clinical and preventive importance.     

Toxicity of lead acetate to female rabbits after chronic subcutaneous administration. 1. Biochemical and clinical effects

The effect of chronic subcutaneous administration of lead acetate was studied in female rabbits. The low-dose group (15 animals) received three times a week 0.10–0.20 g/kg body weight and the high-dose group (15 animals) 0.80–1.20 g/kg. The control group received the vehicle only. Concentrations of lead in blood in the low-dose group increased to ca. 400 g/l after 70 days and in the high-dose group to ca. 900 g/l after 110 days. After 7.5 months eight animals of each group were sacrificed. The remaining rabbits were kept for an additional 4 months without treatment. Blood lead concentrations decreased with a half-time of 60–70 days. During exposure the gain in body weight was lower in the high-dose group than in the control group and the low-dose group. The high-dose group developed slight anaemia and low MCV, MCH and MCHC, and basophilic stippling of erythrocytes. These effects disappeared during recovery. ALAD activity in erythrocytes was very low during exposure in both exposed groups and did not reach control values during recovery. During exposure the concentrations of ZPP and ALA-U increased, but only ALA-U returned to normal during recovery. No other effects of lead on the composition of the urine were observed. No effects were observed on plasma urea and creatinine concentrations. In the highdose group the concentration of ALAD in the liver decreased by 30%. During recovery this effect was no longer present. No effects were seen in cytochrome P-450 content or cytochrome P-450-dependent enzyme activities. Lead was mainly stored in bones, but some also in serveral soft tissues. After recovery the concentrations in soft tissues decreased to a variable degree. In the high-dose group the relative weights of heart and liver increased. These effects disappeared during recovery. At 400 g lead/l blood no adverse effects were observed that did occur at the high dose level.Part 2, dealing with the histopathology and (electron) microscopy of the kidneys is in preparation     

Mechanism of the cardioprotective effect of triamterene in the rat heart. Myocardial protection via elevation of extracellular K+ and Mg++ concentrations

1. 2,4,7-Triamino-6-phenyl-pteridine (triamterene) protects the rat heart against isoproterenol-induced myocardial lesions: Whilst cardiotoxic doses of isoproterenol produce deleterious myocardial Ca overload, simultaneous admistration of triamterene diminishes myocardial Ca incorporation considerably. 2. As to the mechanism of action, triamterene increases the plasma contents of K and Mg by inhibiting renal excretion. Accordingly, oral administration of K and Mg salts, leading to a similar rise in the K and Mg concentrations of the plasma, also prevents abundant myocardial Ca incorporation. 3. Cardioprotection by triamterene can, in fact, be simply explained by its action on the plasma K and (particularly) Mg levels. This conclusion is drawn from a quantitative comparison of the inhibitory effects of triamterene (40 mg/kg s.c.) with those of KCl or MgCl2 (10 mMol/kg p.o.) on the isoproterenol-induced increase in myocardial 45Ca uptake and absolute Ca concentration. 4. Isoproterenol induced cardiomyopathy of the rat, an experimental model of non-coronarogenic myocardial lesions, has hitherto been successfully prevented with the use of Ca-antagonists (verapamil, D 600, prenylamine, fendiline). These compounds reduce Ca influx by restricting the Ca conductivity of the myocardial sarcolemma membrane ("slow channel"). The action of triamterene, on the other hand, is based on a totally different cardioprotective principle, namely competitive inhibition of intracellular myocardial Ca accumulation via an increase in K and Mg supply. In the future treatment of cardiomyopathy it seems rather promising to try a combination of both a Ca-antagonist and triamterene, thus applying two different therapeutic principles simultaneously.     

Early results of a prospective study in patients with computer-assisted femur shaft preparation in total hip endoprosthesis implantation (Robodoc system)--indications, outcome, complications

AIM: Indications, results, advantages and disadvantages of the computer-guided femoral preparation in total hip arthroplasty (Robodoc) in our patients are recorded and represented. METHOD: 41 patients who underwent a computer-guided femoral preparation in total hip arthroplasty (Robodoc) were examined after 1 year on average in a prospective study. The evaluation was made using the Harris Hip Score. The advantages and disadvantages of the Robodoc-assisted surgery are described. RESULTS: More than 80% of the patients had a good or very good result (> 80 points of Harris Hip Score) 3 month after surgery; after 6 months in 20 of 21 patients a score of more than 85 pts. was calculated. The following complications were noticed: thrombotic embolism (2) with one lethal embolism included, fracture of the greater trochanter using the straight stem (3), aseptic drainage due to hematoma (2). 12 patients noticed a postoperative pain at the distal marking pin location (condylus femoris medialis) for an average of 3 months. CONCLUSION: Generally, Robodoc-assisted surgery may be performed in all uncemented total hip arthroplasties. The individual indication should be checked because of the increased effort of surgery, the advantages and disadvantages, and the non-proven better long-term results in comparison to the regular technique. It seems that the Robodoc system provides advantages in post-traumatic arthritis and deformities of the proximal femur (varus and valgus neck) on account of the computer-aided preoperative planning and correct operative realization.     

Urinary acetylated metabolites and N-acetyltransferase-2 genotype in human subjects treated with a para-phenylenediamine-containing oxidative hair dye.

In the organism of mammals, important detoxification pathways of arylamines are catalysed by N-acetyltransferase 2 (NAT2). A recent case-control epidemiology study suggested that human NAT2 slow acetylators exposed to oxidative hair dyes may be at greater risk to develop bladder cancer. We therefore profiled urinary [(14)C]-metabolites and NAT2 genotype in eight human subjects following treatment with a dark-shade oxidative hair dye containing [(14)C]-para-phenylenediamine (PPD). Genotyping identified three subjects as slow, and five subjects as intermediate NAT2 acetylators. Within 24 h after treatment, the study subjects excreted a mean total of 0.43+/-0.24% of the applied [(14)C] in the urine, where five different metabolites were found. The major urinary metabolites were concluded to be N-mono-acetylated and N,N'-diacetylated PPD. They were present in all urine samples and amounted to 80-95% of the total urinary [(14)C]. Another metabolite, possibly a glucuronic acid conjugate, was found in 6/8 urine samples at 5-13% of the total urinary [(14)C]. All metabolites appeared to be related to PPD, no evidence of the presence of high-molecular weight dye-intermediates or corresponding metabolites was found. The metabolite profile in the study subjects showed no significant differences between the NAT2 intermediate and NAT2 slow acetylator subgroups. Urine of NAT2 slow acetylators contained N-mono-acetylated-PPD at 42.2+/-10.2% and N,N'-di-acetylated-PPD at 54.1+/-7.6% of total urinary radioactivity, while the corresponding values of intermediate acetylators were 46.0+/-8.9% and 45.7+/-9.9%, respectively. Overall, our results suggest that the human acetylation rate of PPD after topical application is independent of the NAT2 genotype status, most likely due to metabolism by epidermal NAT1 prior to systemic absorption.     

Diurnal blood pressure variation in the evaluation of early onset severe pre-eclampsia

OBJECTIVE: To study the association between diurnal variation in blood pressure, the mean daily blood pressure and various complications of pregnancy in patients presenting with severe pre-eclampsia before 34 weeks' gestation. STUDY DESIGN: Forty-four women presenting to a tertiary hospital in South Africa with severe pre-eclampsia between 28 and 34 weeks' gestation were managed expectantly for at least 8 days. We measured maternal blood pressure every 30 min with the pregnancy validated Spacelabs 90209 automated blood pressure monitor for 24h periods on alternative days. The mean 24-h diastolic blood pressure measurement, the mean diastolic blood pressure for daytime and nighttime, the day-night blood pressure difference and the night-day ratio were compared with the occurrence of abruptio placentae, gestational age at delivery, neonatal intensive care unit admission, birth weight, abnormal umbilical artery Doppler FVW and reason for delivery. RESULTS: One hundred and seventy-six 24-h studies were analyzed. The day-night blood pressure difference decreased with increasing mean diastolic blood pressure (r=-0.323, p<0.0001). A combination of normal mean diastolic blood pressure and normal day-night blood pressure difference was associated with increased gestational age and lower caesarean section rates. CONCLUSION: The combination of mean diastolic blood pressure and day-night blood pressure difference may be a supplementary measurement of disease severity in early onset severe pre-eclampsia and seems to be of prognostic value.