From occupational medicine to workers' health]

The evolution of the concepts and practice of occupational medicine, occupational health and workers' health is tentatively reviewed. An attempt is made to answer the following questions: what were the major characteristics of occupational medicine throughout its evolution? How and why did occupational medicine evolve into occupational health? Why has the "occupational health model" become inadequate? Within what context did workers' health arise? What are the principal characteristics of workers' health?     

Validity and reliability of three generic outcome measures for hand disorders

This is an assessment of three different outcome measures for the hand: the Hand Clinic Questionnaire (HCQ); the Patient Evaluation Measure (PEM); and the Hand Outcome Survey Sheet (HOSS). Each measure has been tested for its reliability and validity. The results suggest that the PEM and the HCQ are comparably consistent but the PEM is more reproducible. Both the PEM and HOSS are valid questionnaires. The PEM is suitable for use in an outpatient clinic and as a postal questionnaire. The HOSS may be used for research or audit especially when the injury has been measured using the Hand Injury Severity Score.     

Neuropsychiatric evaluation in subjects chronically exposed to organophosphate pesticides.

Long-term exposure to low levels of organophosphate pesticides (OP) may produce neuropsychiatric symptoms. We performed clinical, neuropsychiatric, and laboratory evaluations of 37 workers involved in family agriculture of tobacco from southern Brazil who had been exposed to OP for 3 months, and in 25 of these workers, after 3 months without exposure to OP. Plasma acetylcholinesterase activity levels of all subjects were within the normal range (3.2 to 9.0 U/l) and were not different between on- and off-exposure periods (4.7 +/- 0.9 and 4.5 +/- 1.1 U/l, respectively). Clinically significant extrapyramidal symptoms were present in 12 of 25 subjects, which is unexpected in such a population. There was a significant reduction of extrapyramidal symptoms after 3 months without exposure to OP, but 10 subjects still had significant parkinsonism. Mini-mental and word span scores were within the expected range for this population and were not influenced by exposure to OP. Eighteen of the 37 subjects (48%) had current psychiatric diagnoses in the first interview (13 with generalized anxiety disorder and 8 with major depression). Among the 25 subjects who completed both evaluations, the total number of current psychiatric diagnoses, after 3 months without using OP, dropped from 24 to 13 and the number of affected individuals with any psychiatric diagnosis dropped from 11 to 7. In conclusion, this study reinforces the need for parameters other than acetylcholinesterase activity to monitor for chronic consequences of chronic low-dose OP exposure, and it suggests that subjects have not only transient motor and psychiatric consequences while exposed, but may also develop enduring extrapyramidal symptoms.     

Inhibition of human leukemia in an animal model with human antibodies directed against vascular endothelial growth factor receptor 2. Correlation between antibody affinity and biological activity.

Vascular endothelial growth factor (VEGF) and its receptors (VEGFR) have been implicated in promoting solid tumor growth and metastasis via stimulating tumor-associated angiogenesis. We recently showed that certain 'liquid' tumors such as leukemia not only produce VEGF, but also express functional VEGFR, resulting in an autocrine loop for tumor growth and propagation. A chimeric anti-VEGFR2 (or kinase insert domain-containing receptor, KDR) antibody, IMC-1C11, was shown to be able to inhibit VEGF-induced proliferation of human leukemia cells in vitro, and to prolong survival of nonobese diabetic-severe combined immune deficient (NOD-SCID) mice inoculated with human leukemia cells. Here we produced two fully human anti-KDR antibodies (IgG1), IMC-2C6 and IMC-1121, from Fab fragments originally isolated from a large antibody phage display library. These antibodies bind specifically to KDR with high affinities: 50 and 200 pM for IMC-1121 and IMC-2C6, respectively, as compared to 270 pM for IMC-1C11. Like IMC-1C11, both human antibodies block VEGF/KDR interaction with an IC(50) of approximately 1 nM, but IMC-1121 is a more potent inhibitor to VEGF-stimulated proliferation of human endothelial cells. These anti-KDR antibodies strongly inhibited VEGF-induced migration of human leukemia cells in vitro, and when administered in vivo, significantly prolonged survival of NOD-SCID mice inoculated with human leukemia cells. It is noteworthy that the mice treated with antibody of the highest affinity, IMC-1121, survived the longest period of time, followed by mice treated with IMC-2C6 and IMC-1C11. Taken together, our data suggest that anti-KDR antibodies may have broad applications in the treatment of both solid tumors and leukemia. It further underscores the efforts to identify antibodies of high affinity for enhanced antiangiogenic and antitumor activities.     

Soy protein isolate reduces the oxidizability of LDL and the generation of oxidized LDL autoantibodies in rabbits with diet-induced atherosclerosis

The incidence of atherosclerosis can be modified by diet, and plant-derived proteins have a beneficial effect, but the underlying mechanisms remain unclear. It has been suggested that oxidized LDL (oxLDL) and autoantibodies against oxLDL are important in the development of atherosclerosis. We analyzed these factors in rabbits fed a nonpurified diet supplemented with high cholesterol (10.0 g/kg) containing either 270.0 g/kg casein (CAS, n = 10) or 270.0 g/kg soy protein isolate (SPI, n = 10) for 2 mo. Plasma and purified serum LDL from rabbits were analyzed at d 0, 15, 30, 45 and 60 of treatment, and the size of atherosclerotic lesions was evaluated at d 60 of treatment. CAS-fed rabbits had significantly higher plasma cholesterol at d 15-45 and LDL cholesterol levels at d 15 and 30. Levels of trilinolein and phosphatidylcholine hydroperoxides were higher in the LDL fraction of rabbits fed CAS than in those fed SPI. Also, CAS-fed rabbits had higher levels of highly oxidized LDL [monoclonal antibody (mAb) 24-reactive oxLDL] in plasma at d 60, whereas SPI-fed rabbits had higher levels of minimally oxidized LDL (mAb 28-reactive oxLDL) at d 45. These results were consistent with the earlier formation of anti-oxLDL antibodies and the presence of a larger area of atherosclerotic lesion in rabbits fed the CAS diet. These data indicate the importance of both the type of dietary protein used in the induction of atherosclerosis and the relevance of immunologic mechanisms in addition to biochemical and physiologic factors in the pathogenesis of atherosclerosis.     

Coverage and focus of a cervical cancer prevention program in southern Brazil.

OBJECTIVE: To determine the coverage and focus of cervical cancer screening (Pap smears) in a population-based sample in Brazil. METHODS: Cross-sectional cluster survey covering 1730 women aged 20 years or older with a history of sexual activity. Information was collected on social, demographic and behavioral variables, knowledge of and use of the Pap test. RESULTS: Of women aged 25-59 years, who are the target population of the national cervical cancer screening program, 78.7% had had at least one Pap test in their lifetime, and 68.8% had had a Pap test in the last 3 years. Statistics for focus of the program showed that of the 637 women who reported having a Pap test in the last year, only 20.6% actually required one. The remainder were either outside the age range or had had another test less than 30 months previously. Prevalence of not having been tested in the previous 3 years was highest among black (41.7%) and low-income women (64.3%), and among those at greatest risk for cervical cancer (62.3% for women with three or more risk factors). Focus was inversely related to socioeconomic status. CONCLUSION: Coverage rates were similar to those reported in other national studies, but this is the first report to examine the focus of the national program. We show that 8 of every 10 Pap tests were not necessary. Coverage levels remain unacceptably low among women of low socioeconomic status and those at greatest risk for cervical cancer.     

Hyperglycemia, hyperlipemia, and periodic paralysis: a case report of new side effects of clozapine

1. 1. This case report of a Chinese male schizophrenic patient describes new side effects that have not been documented previously for patients treated with clozapine. At certain doses of clozapine, the patient showed direct adverse reactions, which include a combination of hyperglycemia, hyperlipemia, and periodic paralysis.

2. 2. In a four-year study of this patient who had no previous episodes of diabetes in his or his family history, the authors found that these symptoms disappeared upon withdrawal of clozapine and relapsed with re-treatment of the drug.

3. 3. This study indicates that hyperglycemia, hyperlipemia, and periodic paralysis may need to be monitored on patients treated with clozapine.

     

Pharmacological and structural characterization of a novel phospholipase A2 from Micrurus dumerilii carinicauda venom.

We have isolated a new phospholipase A2 (MiDCA1) from the venom of the coral snake Micrurus dumerilii carinicauda. This toxin, which had a molecular mass of 15,552Da, shared high sequence homology with the PLA2 toxins MICNI A and B from Micrurus nigrocinctus venom (77.7% and 73.1%, respectively). In chick biventer cervicis preparations, MiDCA1 produced concentration- and time-dependent neuromuscular blockade that reached 100% after 120 min (2.4 microM, n = 6); contractures to exogenously applied carbachol (8 microM) and KCl (13 mM) were still seen after complete blockade. In mouse phrenic-nerve diaphragm preparations, MiDCA1 (2.4 microM; n = 6) caused triphasic changes followed by partial neuromuscular blockade. Intracellular recordings of end-plate potentials (EPPs) and miniature end-plate potentials (MEPPs) from mouse diaphragm preparations showed that MiDCA1 increased the quantal content by 386+/-12% after 10 min (n = 14; p<0.05) and caused a triphasic change in the frequency of MEPPs. MiDCA1 also decreased the resting membrane potential, an effect that was prevented by tetrodotoxin and/or low extracellular calcium, but not by d-tubocurarine. The toxin increased the amplitude of mouse sciatic-nerve compound action potentials by 30+/-9% (0.6 microM; p<0.05). Potassium currents elicited in freshly dissociated dorsal root ganglia neurones were blocked by 31+/-1% (n = 4; p<0.05) in the presence of 2.4 microM MiDCA1. These results show that MiDCA1 is a new presynaptic phospholipase A2 that produces neuromuscular blockade in vertebrate nerve-muscle preparations. The triphasic effects seen in mammalian preparations and the facilitatory response were probably caused mainly by the activation of sodium channels, complemented by the blockade of nerve terminal potassium channels. The inability of d-turocurarine to prevent the depolarization by MiDCA1 indicated that cholinergic nicotinic receptors were not involved in this phenomenon.     

Tracheostomy in children: there is a place for acceptable risk

BACKGROUND: Tracheostomy in children remains controversial regarding the risk of complications. METHODS: Forty-six trauma patients (35 male and 11 female, mean age = 6.8 years) were admitted to the intensive care unit between 1987 and 1991 with severe head injury plus coma. Tracheostomy was performed with standard technique after 5.9 days (range, 2-12 days) of intubation. RESULTS: There were no deaths from tracheostomy, but six deaths resulted from severe head injury. One child was discharged with tracheostomy. The 39 survivors remained with tracheostomy 16.14 days (range, 4-71 days) in the intensive care unit. After cannula removal, 31 remained asymptomatic; 8 had respiratory distress: 2 were normal, 5 had endoscopic treatment for subglottic granulomas/stenosis from intubation, and 1 had tracheomalacia from tracheostomy. In 1997, the 18 patients located for follow-up were asymptomatic. At endoscopy, 8 were normal, 9 had subglottal granulomas from intubation, and 1 had 20% tracheal stenosis from tracheostomy. CONCLUSION: Most complications after tracheostomy result from intubation. Tracheostomy has an acceptable risk in children with severe head injury who need prolonged ventilatory support.