A cross-sectional study of triallate exposure and neurological health among workers at a pesticide manufacturing and formulating facility.

AIMS: To evaluate the relation between an indicator of cumulative exposure to triallate and selected measures of neurological function, including nerve conduction, the prevalence of certain neurological deficits as determined by a medical examination, and vibration perception threshold testing in workers at a pesticide manufacturing plant. METHODS: Subjects were 50 workers with high estimated triallate exposure ("high triallate" group) and 50 workers with no or low triallate exposure ("no/low triallate" group). Industrial hygienists used existing work histories and personal knowledge of plant operations to develop a triallate score. In-person interviews elicited information on past medical history and on occupational and non-occupational exposures. A neurologist carried out nerve conduction tests of the sural and the peroneal nerves, a standardised neurological examination, and vibration sensation testing. RESULTS: Differences between the high and the no/low triallate groups were minimal for all but one of the six nerve conduction tests, for the prevalence of neurological abnormalities, and for vibration sensation perception. The high triallate group had lower mean sural nerve peak amplitude than the no/low triallate group (11.7 v 15.2 microV, p = 0.03). This difference was reduced when adjusted for other potential risk factors (12.5 v 14.5 microV, p = 0.25) and was not associated with cumulative triallate score. We also noted several associations between factors other than triallate and nerve conduction measures. CONCLUSION: The results were consistent with the absence of an association between triallate and measures of neurological function.

Spontaneous myopathy in the SJL/J mouse: pathology and strength loss.

Myopathy has been found to develop spontaneously in 100% of SJL/J mice between 6 and 8 months of age. Extent of muscular involvement and mouse strength were quantified in SJL/J mice and Balb/c control mice 2-16 months old. Muscle from young SJL/J mice exhibited histopathological abnormalities and occasional inflammatory infiltrate. By 6 months, 78% of SJL/J mice had developed active myopathy. By 8 months, all SJL/J mice examined had active disease with a mean of 12.9% of muscle fibers affected. Replacement of muscle fibers by fat and/or collagen began at 10 months and was pronounced by 14 months. Significant decreases in strength scores (total body pulling force) at 6 months and 10 months of age reflected the onset of active myopathy and the onset of muscle degeneration, respectively. The spontaneous onset and 100% incidence of myopathy in the SJL/J mouse line should provide a useful model for idiopathic myopathy.

The neuromythology of silicone breast implants.

OBJECTIVE: To define neurologic problems that may occur in women with silicone breast implants. BACKGROUND: The association between silicone breast implants (SBIs) and certain rheumatologic disorders has been discussed since the 1980s. Recent uncontrolled case series have reported neurologic problems believed to be associated with SBIs. DESIGN: Case series based on a retrospective data analysis of medical records from 131 women diagnosed as having a neurologic problem related to SBIs. METHODS: Data extracted from the medical records and analyzed included neurologic symptoms, neurologic examination findings, and a variety of laboratory studies. Symptoms, examination findings, and laboratory studies were analyzed using methods that would purposely overreport false-positive results in order to negate possible bias accusations. Finally, prior diagnoses made by evaluating physicians and thought to be related to SBIs were also recorded. An independent assessment was also made for alternative diagnoses using standards accepted by the medical and neurologic communities which did not necessarily accept a causative link between SBIs and their alleged complications. RESULTS: Neurologic symptoms were frequently endorsed, including fatigue (82%), memory loss and other cognitive impairment (76%), and generalized myalgias (66%). Despite multiple complaints, most patients (66%) had normal neurological examinations. Findings reported as abnormal were mild and usually subjective, including sensory abnormalities in 23%, mental status abnormalities in 13%, and reflex changes in 8%. No pattern of laboratory abnormalities was seen, either in combination or in attempts to correlate them with the clinical situation. Laboratory studies appeared to be random without an attempt to confirm or correlate with a particular diagnosis. Diagnoses by physicians endorsing the concept that SBIs cause illness included "human adjuvant disease" in all cases, memory loss and other cognitive impairment ("silicone encephalopathy") and/or "atypical neurologic disease syndrome" in 73%, "atypical neurologic multiple sclerosis-like syndrome" in 8%, chronic inflammatory demyelinating polyneuropathy in 23%, and some other type of peripheral neuropathy in 18%. There was no coherence in making these diagnoses; the presence of any symptoms in these women was sufficient to make these diagnoses. Alternatively, after review of the data, no neurologic diagnosis could be made in 82%. Neurologic symptoms could be explained in some cases by depression (n=16), fibromyalgia (n=9), radiculopathy (n=7), anxiety disorders (n=4), multiple sclerosis (n=4), multifocal motor neuropathy (n=1), carpal tunnel syndrome (n=1), dermatomyositis (n=1), and other psychiatric disorders (n=3). CONCLUSIONS: There is no evidence that SBIs are causally related to the development of any neurologic diseases. Methods of diagnosis that have been used to make the diagnosis of neurologic disease in these patients are contrary to standards accepted by the neurologic community. Several possible explanations exist for the neurologic and other symptoms in women with breast implants.

Chronic pain is associated with deficits in information processing.

Beginning with the theoretical premise that pain stimuli are liable to perturb the ordinary dynamical state of the brain, we hypothesized that individuals in pain may experience impaired information processing. A sample of 19 persons complaining of chronic pain and a comparison sample of 25 persons having sustained head trauma were obtained by retrospective chart review. The chronic-pain group consisted of 19 persons whose primary complaint was significant chronic pain, with no known history of head trauma or neurologic disorder. The comparison group consisted of 25 persons who had sustained mild to moderate head traumas. All subjects were administered information processing and motor subtests of the Human Performance Measurement System, a computerized set of measures. Both groups obtained mean z scores below the normative mean on all measures except visual digit span. There were no differences between groups on motor measures, visual digit span, and visual-spatial memory. On 2 of 6 information-processing tests, pain patients performed more poorly than head-trauma patients. The results suggest that pain may disrupt cognitive performances which depend on intact speed and capacity of information processing.

Experimental models of inflammatory myopathies.

Several animal models of inflammatory myopathy have been discussed in this review. These include autoimmune (by immunization with muscle antigen and adjuvant), viral-induced, and spontaneous forms. The autoimmune and viral-induced models have limitations as models of the human disorders but because they are relatively well-characterized still have merit in studying immune effector mechanisms of muscle injury. The spontaneous models are less well-characterized, but may nevertheless provide insight into the induction mechanisms of inflammatory muscle diseases. All of these animal models have the potential to provide valuable information which will improve our understanding of the pathogenesis of the human inflammatory myopathies.

Occupational spinal cord injury: demographic and etiologic differences from non-occupational injuries.

Most spinal cord injuries (SCIs) are the result of motor vehicle accidents (MVAs). There are no published reports specifically addressing SCIs that occur in the workplace. We report a cohort survey study examining the frequency and etiology of SCI in the workplace. Through a cooperative program, an evaluation of all SCIs seen in Colorado during a 5 1/2-year period (January 1, 1986 through June 6, 1991) is presented. We report a detailed analysis of specific data of all SCIs occurring in the workplace. There were a total of 566, with 74 (13.1%) due to injuries that occurred during the course of employment. The most common cause of occupational SCI was falls, which occurred in 37 (50%), as compared with only 15.9% of non-occupational SCIs. Only 14 (18.9%) occupational SCIs resulted from MVAs, compared with 59.3% of non-occupational SCIs. Other major etiologies for occupational SCI included being hit by a falling object in 14 individuals (18.9%), gunshot wound in three (4%), skiing in one (1.4%), stabbing in one (1.4%), and other causes in four (5.4%). Construction occupations were over-represented in occupational SCIs with 41.9% of cases as compared with only 6.3% for the non-occupational group. Because of the large percentage of occupational SCIs, efforts should be aimed at educating workers in at-risk occupations to prevent this serious injury.

Intensive rehabilitative approach to eosinophilia myalgia syndrome associated with severe polyneuropathy.

We report a case of the eosinophilia myalgia syndrome (EMS) with incapacitating myalgias, weakness secondary to a severe polyneuropathy, and contractures in all four extremities requiring aggressive rehabilitation treatment. A 55-year-old woman was admitted to a rehabilitation hospital 11 months after the onset of EMS. At that time, she had severe weakness secondary to peripheral neuropathy and painful contractures in all extremities and required high doses of narcotics for pain control. A continuous passive range of motion machine was used in order to maintain range of motion obtained during active exercise therapy. The patient showed functional improvement in basic mobility and ADL skills. She was withdrawn from narcotics and successfully learned pain management techniques. An aggressive rehabilitation approach in the treatment of EMS associated with peripheral neuropathy may improve functional outcome even when instituted late in the clinical course.

Survival of implanted fetal dopamine cells and neurologic improvement 12 to 46 months after transplantation for Parkinson's disease.

BACKGROUND AND METHODS: Patients with Parkinson's disease tend to have a reduced response to levodopa after 5 to 20 years of therapy, with "on-off" fluctuations consisting of dyskinesia alternating with immobility. In an effort to modify the motor disability of advanced Parkinson's disease, we implanted embryonic mesencephalic tissue containing dopamine cells into the caudate and putamen of seven patients. Two patients received unilateral grafts in the caudate and the putamen on the side opposite the side with worse symptoms. Five patients received bilateral grafts implanted in the putamen only. In six of the seven patients, the fetal tissue was obtained from a single embryo with a gestational age of seven to eight weeks. The tissue was injected by means of 10 to 14 needle passes. There were no surgical complications. Four of the seven patients underwent immunosuppression with cyclosporine and prednisone. RESULTS: All patients reported improvement according to the Activities of Daily Living Scale when in the on state 3 to 12 months after surgery (P < 0.01). Neurologic examination according to the Unified Disease Rating Scale showed that five of the seven patients improved when in the on state six months after surgery. The mean group Hoehn-Yahr score improved from 3.71 to 2.50 (P < 0.01). Computer and videotape testing in the home supported these findings. Fluctuations in clinical state were moderated, and periods of dyskinesia and off episodes were shorter and less severe than before implantation. Drug doses were reduced by an average of 39 percent (P < 0.01; maximum, 58 percent). The results of clinical evaluation and fluorodopa positron-emission tomography in one patient were compatible with transplant survival for as long as 46 months. Both immunosuppressed and nonimmunosuppressed patients improved. CONCLUSIONS: Fetal-tissue implants appear to offer long-term clinical benefit to some patients with advanced Parkinson's disease.

Transplantation of human fetal dopamine cells for Parkinson's disease. Results at 1 year.

In an effort to improve the clinical signs of Parkinson's disease, we have implanted mesencephalic dopamine cells from a 7-week human embryo into the caudate and putamen of a 52-year-old man with Parkinson's disease. Fetal tissue was obtained from elective abortion. The woman and the patient with Parkinson's disease were unknown to each other. The woman gave specific consent and was not paid. The patient had a 20-year history of parkinsonism treated with multiple drug therapies including levodopa/carbidopa (Sinemet) every 2 1/2 hours. His symptoms were worse on the left side. For 5 months prior to transplantation, the patient underwent clinical evaluations by both a neurologist and a computer system installed in his home for daily measurement of walking and hand movements. Preoperative positron emission tomographic scanning with 6-L[18F]fluorodopa (fluorodopa) demonstrated severe dopamine depletion bilaterally. Fetal tissue was matched to the patient for ABO blood antigens, and maternal serum was screened for hepatitis B and human immunodeficiency virus type 1 prior to surgery. Fetal tissue was implanted stereotactically throughout the caudate and putamen on the right side of the brain via 10 needle tracks. The patient was not immunosuppressed. Results 12 months after surgery showed 42% improvement in left-hand speed before the first morning dose of drug and 40% greater response to drug therapy. Right-hand speed increased 15% before drug therapy and 23% after drug therapy. Reaction time was unaffected. Walking speed increased 33% after drug administration, although walking speed before the first morning dose of drugs declined 40%. Walking speed on an all-day basis improved 17%.(ABSTRACT TRUNCATED AT 250 WORDS)

White matter dementia in chronic toluene abuse.

We studied 14 chronic toluene abusers with a comprehensive neuropsychological evaluation and cerebral magnetic resonance imaging (MRI). There were 10 men and 4 women, and the mean age was 29 years. Using a blinded global assessment of neuropsychological functioning, we found 3 patients to be normal, 3 in a borderline range, and 8 impaired. Independent analyses of white matter changes on MRI disclosed that the degree of white matter abnormality was strongly correlated (p less than 0.01) with neuropsychological impairment. Dementia in toluene abuse appears to be related to severity of cerebral white matter involvement.

Evidence for a novel picornavirus in human dermatomyositis.

We prepared RNA probes from cloned segments of human and murine enteroviruses (EVs) for in situ hybridization of skeletal muscle biopsies from patients with dermatomyositis (DM), polymyositis, other inflammatory myopathies, and noninflammatory muscle diseases, and from normal control subjects. A probe derived from Theiler's murine encephalomyelitis virus (TMEV) detected viral RNA within mononuclear cells of the interstitial connective tissue in 3 of 5 patients with adult-onset DM. None of these patients showed positive hybridization to probes derived from human EVs (poliovirus type 1 and Coxsackie virus B3) applied to subjacent sections of the same biopsies. The remaining 2 adult DM patients, 4 patients with childhood-onset DM, and 24 non-DM patients did not react with either TMEV or human enterovirus probes. Histochemical stains for esterase and immunoperoxidase stains for Mac-1 antigen in the 3 DM patients who reacted positively revealed positive cells in the same distribution as, but in far greater number than, those positive by in situ hybridization. Immunoperoxidase staining for HLA-DR antigens revealed positive cells in the same distribution and number as were seen with the TMEV probe. We conclude that an EV-like agent, more closely related to TMEV than to human EVs, may be associated with DM and that this agent is probably localized within muscle macrophages that express class II major histocompatibility complex antigens.

Aberrant expression of class II MHC antigens by skeletal muscle endothelial cells in experimental autoimmune myositis.

We recently described the induction of an inflammatory myopathy in SJL/J mice after injection of skeletal muscle Ag and adjuvant that is characterized by necrosis of muscle fibers associated with infiltrating mononuclear cells. In the present study, an immunohistologic analysis was performed to examine the phenotype of these infiltrating cells and to determine changes in cell-surface Ag expression in involved muscle. The predominant cells infiltrating muscle after induction of experimental autoimmune myositis (EAM) were found to be Mac-1+/I-A+ macrophages, representing 80 to 90% of all infiltrating cells, and CD4+ T lymphocytes, representing 10 to 15% of all infiltrating cells. Few CD8+ T cells, and no B cells, were seen in the involved muscles. Interestingly, endothelial cells in involved muscles were also noted to express class II MHC Ag. Aberrant I-A Ag expression was not observed on endothelial cells in other tissues examined, including kidney, liver, cardiac muscle, and lung. I-A Ag expression appeared to correlate with susceptibility to disease in that muscle endothelial cells remained negative after attempts to induce EAM in a nonsusceptible strain. Together, the data suggest that aberrant organ-specific class II MHC Ag expression and a response by CD4+ T cells may be pathogenetically involved in the muscle injury of EAM. In addition, the predominance of infiltrating macrophages suggests that these recruited cells may also be important in the immune-mediated muscle damage.

Immunolocalization of a subnucleolar nucleoprotein complex containing RNA polymerase 1 in ascites hepatoma cells using monoclonal antibodies.

We have isolated a discrete subnucleolar macromolecular nucleoprotein complex by direct treatment of Novikoff ascites hepatoma nucleoli by MspI restriction digestion. Using a monoclonal antibody made against the subnucleolar nucleoprotein complex that was shown to inhibit RNA polymerase (pol) 1 activity in vitro, we localized an Mr approximately 55,000 protein subunit which was demonstrated previously by an enzyme-linked immunosorbent assay and Western blotting to share epitopes with the RNA pol 1 moiety of the subnucleolar complex. By indirect immunofluorescence the distribution of the Mr approximately 55,000 component of the subnucleolar nucleoprotein complex was examined at various phases of the cell cycle. At prophase, it was localized in large (approximately 1.5 microns in diameter) ball-like structures associated with the nuclear periphery and nuclear peripheral chromatin, suggesting that these structures might be related to preribosomal elements. After chromatin condensation and the pairing of daughter chromosomes, the large ball-like spheres increased in size and were associated with propidium iodide staining at one side of the nucleus; whereas throughout and especially at the opposite side of the nucleus, smaller, round, punctate structures of approximately 0.5 micron in diameter were visibly labeled that were not associated with propidium iodide staining. At later stages of the cell cycle, these small round structures were again associated with propidium iodide staining, suggesting that they may be related to prenucleolar and/or preribosomal elements which would likely contain the appropriate nucleic acid in association with RNA pol 1 and cofactors of RNA pol 1.

Cyanide-induced parkinsonism: clinical, MRI, and 6-fluorodopa PET studies.

A 46-year-old man ingested 1,500 mg of potassium cyanide in a suicide attempt. He survived, but later developed a severe parkinsonian syndrome. MRI revealed multiple areas of low-signal intensity in the globus pallidus and posterior putamen. A 6-fluorodopa PET study revealed bilateral decreased uptake in the basal ganglia. This evidence of functional impairment of dopaminergic nigrostriatal neurons is related either to direct toxicity of cyanide or to the effects of cerebral hypoxia secondary to cyanide intoxication.