A cohort study of cancer mortality among Biology Research Laboratory workers in The Netherlands

OBJECTIVE: To examine cancer mortality among persons employed in biology research institutes. METHOD: A historical cohort study was undertaken in the Netherlands. The cohort, comprising 7307 laboratory workers employed by the four participating institutes between 1960 and 1992, was followed for mortality from 1960 to 1995 (median follow-up time 16.5 years). Causes of death were obtained for 98% of all deaths. Cancer mortality in the cohort was compared with that in the general population by computation of the standardized mortality ratio (SMR). The Cox proportional hazards model was used to compare cancer mortality among laboratory workers with that in an internal reference population consisting of unexposed research personnel (n = 2,404). RESULTS: All-cause mortality among laboratory workers was significantly lower than that in the general population. Total cancer mortality and lung cancer mortality were also significantly decreased (SMR = 0.8; 95% confidence interval CI = 0.7-0.9 and SMR = 0.7; 95% CI = 0.6-0.9), respectively. However, when compared to the internal reference population, laboratory workers had a slightly increased cancer mortality (relative risk (RR) = 1.3 95% CI = 0.9-1.9). Among men, a 2.5-fold (95% CI = 1.0-6.3) increase of lung cancer mortality was observed which could not be explained by differences in smoking habits. Lung cancer mortality increased with longer follow-up. Results with regard to a priori defined fields of research showed significantly increased cancer mortality (in particular from lung cancer) for men working in genetics (RR = 3.8), virology (RR = 4.1) and plant physiology (RR = 2.1). CONCLUSION: Laboratory workers have a favorable cancer mortality pattern as compared to the general population. However, this favorable pattern disappears when a comparison is made with a control group of unexposed research personnel. The excess lung cancer mortality among male laboratory workers was concentrated in certain fields of research, which warrants further research to identify specific exposures related to the increased risk.     

Discordant mental and physical efforts in an autistic patient

We investigated whether there was mental effort in response to verbal commands in a 16-year old girl with autism, a high degree of non-compliance with commands and symptoms of autonomic dysfunction by monitoring the brainstem autonomic tone during an attempt to perform isometric exercise. An index of cardiac vagal tone (CVT), cardiac sensitivity to baroreflex (CSB), heart rate (HR) and mean arterial blood pressure (MAP) were measured simultaneously. Physical non-compliance with our commands meant there was no force applied by the patient during the attempted exercise, but CVT and CSB were both reduced and sustained at very low levels throughout the attempt, while MAP and HR were increased concurrently to higher levels in the same period. This vagal withdrawal to allow concurrent increases in HR and MAP is an arousal response appropriate for isometric exercise, which is a sign of a positive mental effort to comply with our commands. These results demonstrate discordant mental and physical efforts in our patient. In this particular case, the physical inabilities in some instances could have been mislabelled as mental non-compliance due to autism. It would be worthwhile to investigate the prevalence of discordant mental and physical efforts in autism.     

Therapeutic potential of monoisoamyl and monomethyl esters of meso 2,3-dimercaptosuccinic acid in gallium arsenide intoxicated rats

The dose dependent effects of monoisoamyl and monomethyl esters of meso 2,3-dimercaptosuccinic acid (DMSA) (0.1, 0.3 and 0.5 mmol kg(-1), intraperitoneally (i.p.) once daily for 5 days) to offset the characteristic biochemical, immunological, oxidative stress consequences and DNA damage (based on DNA fragmentation and comet assay) following sub-chronic administration of gallium arsenide and the mobilization of gallium and arsenic were examined. The effects of these chelators alone in normal animals too were examined on above-mentioned variables. Male Wistar rats were exposed to 10 mg kg(-1), GaAs, orally once daily for 12 weeks and were administered DMSA or two of its monoesters (monoisoamyl or monomethyl) for 5 consecutive days. DMSA was used as a positive control. DMSA and its derivatives, when given alone, generally have no adverse effects on various parameters. After 5 days of chelation therapy in GaAs pre-exposed rats, MiADMSA was most effective in the reduction of inhibited blood delta-aminolevulinic acid dehydratase (ALAD) activity and zinc protoporphyrin level while, all three chelators effectively reduced urinary ALA excretion, compared to GaAs alone exposed rats. MiADMSA was also effective, particularly at a dose of 0.3 mmol kg(-1), in enhancing the inhibited hepatic transaminase activities. Parameters indicative of oxidative stress responded less favorably to the chelation therapy, however, three chelators significantly restored the altered immunological variables. MiADMSA was relatively more effective than the other two chelators. GaAs produced significant DNA damage in the liver and kidneys and the chelation treatment had moderate but significant influence in reducing DNA damage. All three chelators significantly reduced arsenic concentration and, however, MiADMSA was more effective than the other two chelators in depleting arsenic concentration from blood and other soft tissues. A dose of 0.3 mmol kg(-1) was found to be relatively better than the other two doses examined. Gallium contents of blood and soft tissues remained uninfluenced by the chelation therapy. Significant loss of copper after MiADMSA administration, however, is of concern and requires further exploration. Additionally, further studies are required for the choice of appropriate dose, duration of treatment and possible toxic/side effects. Keeping in view the promising role of MiADMSA in the treatment of GaAs poisoning, these data will be needed for the registration of this chelating agent as licensed drug for the treatment of gallium arsenide intoxication.     

Current state of intraoperative echocardiography

Intraoperative use of echocardiography is becoming more prevalent and is now considered an essential part of modern cardiac surgery. Echocardiography can be performed intraoperatively using transesophageal, epicardial or epiaortic, and substernal approaches. These techniques have a variety of applications in evaluating myocardial and valvular function, assessing aortic atheroma, and determining adequacy of various kinds of repair and reconstruction. Future applications will most likely involve more compact equipment, the implementation of epicardial and transesophageal real-time three-dimensional echocardiography, and better use of provocative methods of intraoperative testing.     

Sequential expressions of MMP-1, TIMP-1, IL-6, and COX-2 genes in induced periapical lesions in rats

To elucidate the pathogenesis of periapical lesion-associated bone resorption, a disease model of Wistar rat molar was employed. After lesion induction, the mRNAs encoding for matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) in the developing lesions were detected by in situ hybridization at day 5, 10, 15 and 20, respectively. At day 5, MMP-1, IL-6 and COX-2 mRNAs appeared predominantly in macrophages. During day 15 to day 20, increased expressions of these mediators were also found in osteoblasts but to a lesser extent compared with those in macrophages. MMP-1 mRNA was also detected in osteoclasts. In contrast, expression of the TIMP-1 gene was noted primarily in osteoblasts and was less pronounced compared with that of MMP-1. The mediator-expressing cells aggregated in the vicinity of bone resorption areas and their numbers increased with time. These data suggest that macrophages and osteoblasts are involved in the development of periapical lesions, and that they promote bone resorption by producing MMP-1, IL-6 and COX-2. In addition, administration of a specific COX-2 inhibitor, meloxicam, reduced the extent of periapical bone resorption by 43% and simultaneously diminished the numbers of cells synthesizing MMP-1 and IL-6 mRNAs. These results further elucidate the significance of COX-2 in disease progression of periapical lesions as it modulates indirectly the production of MMP-1 and IL-6.     

Reversal of statin toxicity to human lymphocytes in tissue culture

Hydroxymethylglutaryl-CoA reductase inhibitors (statins) are widely used to inhibit biosynthesis of cholesterol in individuals with elevated serum levels of this risk factor for cardiovascular disease. We find that statins are toxic to human lymphocytes in cell culture at concentrations less than 0.1 microg/ml. Addition of their own plasma reverses this toxicity in some, but not all, individuals. Addition of coenzyme Q10 (CoQ10) with plasma is more effective than plasma alone in reversing toxicity in some individuals. Apparently, two factors are required to reverse the cellular toxicity of statins: CoQ10 and a plasma factor found in a subset of individuals. These observations may provide the basis for a method to assess individual susceptibility to statin toxicity and to predict which individuals may benefit from supplements of CoQ10.     

Struma ovarii coexisting with mucinous cystadenoma detected by radioactive iodine

The authors describe a case of struma ovarii coexisting with mucinous cystadenoma. Ultrasonography and magnetic resonance imaging showed a multilocular cystic mass with a solid component. The ovarian tumor demonstrated uptake of I-123 sodium iodide, allowing a preoperative diagnosis of struma ovarii. In women with an unexplained increase in thyroid function and low I-123 uptake in the cervical thyroid gland, scintigraphy of the pelvis should be considered.