Denture cream: an unusual source of excess zinc, leading to hypocupremia and neurologic disease.

BACKGROUND: Chronic, excess zinc intake can result in copper deficiency and profound neurologic disease. However, when hyperzincemia is identified, the source often remains elusive. We identified four patients, one previously reported, with various neurologic abnormalities in the setting of hypocupremia and hyperzincemia. Each of these patients wore dentures and used very large amounts of denture cream chronically. OBJECTIVE: To determine zinc concentration in the denture creams used by the patients as a possible source of excess zinc ingestion. METHODS: Detailed clinical and laboratory data for each patient were compiled. Tubes of denture adhesives were analyzed for zinc content using dynamic reaction cell-inductively coupled plasma-mass spectrometry. Patients received copper supplementation. Copper and zinc levels were obtained post-treatment at varying intervals. RESULTS: Zinc concentrations ranging from about 17,000 to 34,000 mug/g were identified in Fixodent and Poli-Grip denture creams. Serum zinc levels improved in three patients following cessation of denture cream use. Copper supplementation resulted in mild neurologic improvement in two patients who stopped using denture cream. No alternative source of excess zinc ingestion or explanation for hypocupremia was identified. CONCLUSION: Denture cream contains zinc, and chronic excessive use may result in hypocupremia and serious neurologic disease.

The computerized perinatal database: are the data reliable?

The purpose of this study is to examine the correctness of the clinical data from the computerized perinatal database (PC-Log) at a Mayo Health System hospital. This computerized database is used for electronic transmission of birth certificates in Wisconsin. The paper medical record is chosen for the comparison. Random selection of 99 charts from a total of 893 births at a tertiary perinatal center during 1995. Of 310 fields in the database, 32 variables were compared to a hand abstraction of the paper medical record. PC-Log had 100% positive-predictive value (PPV) for eclampsia, prolonged rupture of membranes, pre-existing diabetes, cesarean section, and transports. The sensitivity, specificity, and PPV for other variables (abortion, congenital anomalies, gestational diabetes, maternal hypertension, and maternal employment) showed moderate to high agreement, but was poor for maternal ethanol use during pregnancy. Compared to hand abstraction, PC-Log had no recorded cases of substance abuse, antenatal steroids, hyaline membrane disease, circumcision, maternal and infant length of stay. Means for birth weight 5 minute Apgar scores did not differ, and the correlations were r = 0.982 and r = 0.960. The PC-Log showed good agreement for many but not all the variables of clinical interest.

Clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy.

OBJECTIVE: To describe the clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy (IIM) and to compare these with the features of sporadic IIM. METHODS: Clinical signs and symptoms, autoantibodies, HLA-DRB1 and DQA1 alleles, and GM/KM phenotypes were compared among 36 affected and 28 unaffected members of 16 unrelated families in which 2 or more blood relatives developed an IIM. In addition, findings in patients with familial IIM were compared with those in 181 patients with sporadic IIM. The families included 3 pairs of monozygotic twins with juvenile dermatomyositis, 11 families with other siblings or relatives with polymyositis or dermatomyositis, and 2 families with inclusion body myositis. RESULTS: The clinical features of familial IIM were similar to those of sporadic IIM, although the frequency of myositis-specific autoantibodies was lower in familial than in sporadic IIM. DRB1*0301 was a common genetic risk factor for familial and sporadic IIM, but contributed less to the genetic risk of familial IIM (etiologic fraction 0.35 versus 0.51 in sporadic IIM). Homozygosity at the HLA-DQA1 locus was found to be a genetic risk factor unique to familial IIM (57% versus 24% of controls; odds ratio 4.2, corrected P = 0.002). CONCLUSION: These findings emphasize that 1) familial muscle weakness is not always due to inherited metabolic defects or dystrophies, but may be the result of the development of IIM in several members of the same family, and 2) multiple genetic factors are likely important in the etiology and disease expression of familial IIM, as is also the case for sporadic myositis, but DQA1 homozygosity is a distinct risk factor for familial IIM.

Chaparral-associated hepatotoxicity.

BACKGROUND: Personal health care practices that may include the use of dietary supplements are common in the United States. Products marketed as dietary supplements are diverse and may include botanicals, vitamins, and/or minerals. Chaparral (Larrea tridentata) is a botanical dietary supplement made from a desert shrub and used for its antioxidant properties. Several reports of chaparral-associated hepatitis have been published since 1990, but a complete picture of the clinical presentation is still unclear. MATERIALS AND METHODS: We reviewed the 18 case reports of adverse events associated with the ingestion of chaparral reported to the Food and Drug Administration between 1992 and 1994. These reports were from health care professionals, state health departments, and individual consumers. RESULTS: Of 18 reports of illnesses associated with the ingestion of chaparral, there was evidence of hepatotoxicity in 13 cases. Clinical presentation, characterized as jaundice with a marked increase in serum liver chemistry values, occurred 3 to 52 weeks after the ingestion of chaparral, and it resolved 1 to 17 weeks after most individuals stopped their intake of chaparral. The predominant pattern of liver injury was characterized as toxic or drug-induced cholestatic hepatitis; in 4 individuals, there was progression to cirrhosis; and in 2 individuals, there was acute fulminant liver failure that required liver transplants. CONCLUSIONS: These data indicate that the use of chaparral may be associated with acute to chronic irreversible liver damage with fulminant hepatic failure, and they underscore the potential for certain dietary supplement ingredients to cause toxic effects on the liver. Health professionals should be encouraged to inquire routinely about the use of dietary supplements and other products, to be alert to potential adverse effects that may be associated with these products, and, finally, to report any serious adverse events associated with these products through the MEDWatch Program of the Food and Drug Administration.

Adapting mobile robotic technology to intralaboratory specimen transport.

OBJECTIVE: To evaluate and implement two identical inexpensive robotic vehicles for transport of patient specimens within our clinical laboratory. DESIGN: We accepted delivery of the first two robotic vehicles produced by a local vendor and studied the vehicles for 13 months. The first 4 months of familiarization and customization were followed by 9 months of routine use. SETTING: Within the specimen-processing, hematology, and chemistry sections of a large academic medical center's clinical laboratory, one floor below ground. INTERVENTION: The vehicles replaced 1.5 individuals who transported specimens. OUTCOME MEASURES: The number of kilometers the vehicles traveled and the number of routes begun, completed, not completed, and with unknown status. In addition, we assessed the types of problems that occurred, employee satisfaction, and financial payback. RESULTS: When used on all shifts for 13 months, the vehicles traveled an average of over 2000 routes and 212 km per month. At any one time, at least one vehicle was operational. Of the 17 problems that occurred, the most frequent were navigational problems caused by obstacles, such as personnel, in the vehicle's right-of-way. For 6 of the last 9 months, navigational, mechanical, and electronic problems together occurred no more than two or three times per week. Financial payback for the vehicles occurred in less than one year. CONCLUSIONS: By the end of the study, the robotic vehicles completed 99.4% of their routes. Specimen-processing and transport personnel reported the vehicles made their jobs easier and improved timeliness of specimen delivery. We anticipate our potential savings over 5 years to be approximately $200,000 (US).

Focal myositis presenting as pseudothrombophlebitis of the neck in a patient with mixed connective tissue disease.

This report describes a case of focal myositis in a patient with mixed connective tissue disease. The patient presented with diffuse neck swelling and pseudothrombophlebitis of the left internal jugular vein. Other clinical features included a high fever, elevated erythrocyte sedimentation rate, and prompt improvement after administration of high-dose intravenous corticosteroid therapy. Criteria for polymyositis were absent, serum levels of creatine kinase remained normal, and there was no sign of recurrence during 3 years of followup. Results of immunoprecipitation for anti-Jo-1 and other myositis-specific autoantibodies remained negative in serial serum samples obtained before, during, and after the episode.

New environmental agents associated with lupus-like disorders.

An increasing number of environmental agents are being investigated as possible risk factors in the etiology of certain connective tissue disorders. Exposure to a variety of therapeutic agents, foods and dietary supplements, occupational and other toxic exposures, and infectious agents has been associated with the onset of lupus-like disorders. The mechanisms by which these agents might induce lupus remain unknown but may involve alteration of cellular components or activation of the immune system. Individual host susceptibility factors, including pre-existing organ dysfunction and particular metabolic enzyme or immunogenetic phenotypes, may also be important risk factors for development of environmentally-associated lupus-like disorders. Awareness of the many environmental agents implicated with lupus and related disorders, and dissection of their pathogenetic mechanisms through appropriate case-controlled investigations, may identify additional toxic agents and may lead to a better understanding of the idiopathic lupus syndromes.

An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan.

OBJECTIVE: To determine whether L-5-hydroxytryptophan (L-5-HTP) associated with eosinophiliamyalgia syndrome (EMS) like illness contains impurities in a fashion similar to that described in L-tryptophan associated with EMS. METHODS: Members of a family who became ill after exposure to L-5-HTP were evaluated at the National Institutes of Health. Data from patients with extended exposure to L-5-HTP were also examined. Samples of L-5-HTP were examined using high performance liquid chromatography. RESULTS: One member of the family had EMS, and 2 others had eosinophilia. No patient in the other group reviewed developed the syndrome, although 2 patients developed eosinophilia. The L-5-HTP used by the family contained an impurity not present in samples from the other patient group. After replacement with L-5-HTP not containing this impurity, eosinophilia in 2 family members resolved. CONCLUSION: Some L-5-HTP contains impurities that may be related to L-5-HTP associated EMS.

Regression of experimental Burkitt's lymphoma induced by Epstein-Barr virus-immortalized human B cells.

Epstein-Barr virus (EBV)-immortalized human B cells survive only transiently when injected subcutaneously into athymic mice, whereas Burkitt's lymphoma cells give rise to progressively growing subcutaneous tumors. In this study, we tested whether these Burkitt's tumors could be induced to regress via a bystander effect induced by EBV-immortalized B cells. Simultaneous inoculation of EBV-immortalized B cells and Burkitt's lymphoma cells in the same subcutaneous site resulted in tumors that regressed with necrosis and scarring. Similarly, simultaneous inoculation of EBV-immortalized B cells and Burkitt's lymphoma cells in separate subcutaneous sites resulted in regression of a proportion of the Burkitt's tumors. Furthermore, most of the established human Burkitt's tumors regressed with necrosis and scarring after intratumor inoculations with EBV-immortalized B cells. The EBV-immortalized B cells continued to exert this antitumor effect even when killed with irradiation. The experimental approach to Burkitt's lymphoma treatment described here exploits the ability of athymic mice to reject EBV-immortalized B cells to target an effective antitumor response to malignant cells normally incapable of eliciting it.

Noninfectious environmental agents associated with myopathies.

Increasing attention is being focused on environmental agents as possible factors in the etiology of certain connective tissue disorders. As our awareness in this area increases, the number and diversity of these agents is expanding yearly and now includes, in addition to infectious agents, a variety of foods and dietary supplements, drugs, occupational and other toxic exposures, biologics, and medical devices. Some of these agents have been associated with the development of muscle disease through mechanisms that involve alterations in the vascular supply to muscle, depletion of electrolytes, direct toxic effects on mitochondria or other metabolic processes, or activation of the immune system. Individual host susceptibility factors, including preexisting organ dysfunction and particular metabolizer or immunogenetic phenotypes, also appear to be important for development of the clinical syndromes identified as environmentally associated myopathies. Although data in this area are limited, they suggest that when susceptible individuals are exposed to selected agents, physiologic alterations occur that lead to myopathy. Physician awareness of chemicals implicated with myopathy and dissection of their pathogenetic mechanisms through human and animal studies may aid in the identification of additional toxic agents, minimize new cases in the future, and lead to a better understanding of the idiopathic myopathies.

Myopathy with mitochondrial alterations in patients with primary biliary cirrhosis and antimitochondrial antibodies.

OBJECTIVE: To describe a syndrome of severe progressive myopathy, cardiomyopathy, and gastrointestinal dysmotility in 2 patients with asymptomatic primary biliary cirrhosis (PBC) and circulating antimitochondrial autoantibodies, and to review pertinent literature concerning this syndrome. METHODS: Clinical, electrophysiologic, serologic, and pathologic studies of the 2 affected patients were conducted. RESULTS: Skeletal muscle involvement was manifested by progressive weakness of the proximal muscles, marked diaphragmatic dysfunction with consequent hypoventilation and respiratory failure, and moderately elevated levels of muscle-associated enzymes. Serum from both patients contained antimitochondrial antibodies that reacted with components of the mitochondrial keto acid dehydrogenase enzyme complex. Results of electromyography were consistent with a myopathic process. The microscopic and ultrastructural changes in the skeletal muscles were distinct from those of typical myositis, and were notable for striking subsarcolemmal aggregation of abnormal mitochondria in the absence of significant inflammation. CONCLUSION: Severe skeletal muscle, cardiac, and gastrointestinal pathology with abnormalities of the muscle mitochondria develops in a subset of patients with mild PBC and antimitochondrial antibodies. The pathogenesis of this syndrome is unclear, but may be related to the presence of the antimitochondrial autoantibodies.

Drug therapy of the idiopathic inflammatory myopathies: predictors of response to prednisone, azathioprine, and methotrexate and a comparison of their efficacy.

PURPOSE: To identify factors associated with responses to treatment with prednisone, methotrexate, or azathioprine in patients with idiopathic inflammatory myopathy, and to compare the efficacy of these drugs. PATIENTS AND METHODS: Data were collected on 113 adult patients meeting criteria for definite idiopathic inflammatory myopathy in this retrospective cohort study. Patients were categorized as responding completely, partially, or not at all to each therapeutic trial based upon clinical and laboratory criteria. RESULTS: Clinical group, presence of certain myositis-specific autoantibodies, and time from disease onset to diagnosis influenced rates of complete clinical response to these therapeutic agents. Patients with inclusion body myositis responded comparatively poorly to prednisone and the other drugs: 43% had no clinical response to prednisone and none responded completely to any medication. Patients with autoantibodies to aminoacyl-tRNA synthetases or to signal recognition particle proteins were likely to respond partially, but not completely, to prednisone. No patient with a long delay to diagnosis (greater than 18 months) responded completely, compared with 34% of those with a short delay (less than 3 months). A patient's response to the first course of prednisone predicted subsequent responses to prednisone and to azathioprine better than response to methotrexate. Men responded to methotrexate better than women. Among certain subgroups of patients, responses to methotrexate were better than to either azathioprine or retreatment with prednisone. CONCLUSION: Determining the clinical group, autoantibody status, and time from disease onset to diagnosis of patients with myositis provides useful information in predicting clinical responses to therapy, and these factors should be considered in designing future therapeutic trials. Methotrexate therapy may be superior to either azathioprine or further steroid treatment alone in certain patients who do not respond completely to an initial adequate course of prednisone.

Pathological and immunological effects of ingesting L-tryptophan and 1,1'-ethylidenebis (L-tryptophan) in Lewis rats.

The eosinophilia-myalgia syndrome (EMS) has been associated with ingestion of L-tryptophan (L-TRP) produced by a single manufacturer. Epidemiological data implicated 1,1'-ethylidenebis (L-tryptophan) (EBT) (peak 97 or peak E) as a possible etiologic agent. We showed previously that Lewis rats treated with the L-TRP implicated in EMS develop fasciitis and perimyositis similar to those seen in human EMS. We now report the pathology associated with the treatment of Lewis rats with synthetic EBT and/or L-TRP. All animals treated for 6 wk with case-associated L-TRP or EBT developed significant myofascial thickening, compared with animals in the vehicle control and control L-TRP groups. However, even those animals receiving the control L-TRP showed a mild but significant increase in the thickness of the myofascia, compared with vehicle-treated control animals. All animals except vehicle controls also exhibited significant pancreatic pathology, including fibrosis and acinar changes. Only animals treated with case-associated L-TRP for 6 wk showed evidence of immune activation with increased frequency of CD8, Ia, and IL-2 receptor-positive cells in the peripheral blood. Animals receiving L-TRP or EBT for < 6 wk did not show significant differences in myofascial thickness, although these animals did show pancreatic acinar changes. Although these results demonstrate for the first time the pathological effects of EBT, they do not rule out the possibility that other impurities in the EMS-case-associated L-TRP may also contribute to some of the features of EMS.

Pathologic changes in the cardiac interstitium of mice infected with encephalomyocarditis virus.

Patients with myocarditis often develop dilated cardiomyopathy and congestive heart failure. Histologically, myocarditis is manifested by rare foci of myocyte necrosis with interstitial inflammation, while cardiomyopathy is characterized by diffuse interstitial fibrosis, myocyte hypertrophy, and an absence of active interstitial inflammation. The relationship between myocardial inflammation and interstitial fibrosis is poorly understood. This relationship was examined in mice that developed a diffuse interstitial inflammation of the heart over a period of 21 days following infection with encephalomyocarditis virus. Typical early lesions (day 7) included focal zones of myocytolysis containing mononuclear and polymorphonuclear inflammatory cells that were associated with the focal loss of reticular fibers. Later pathology (days 14-21) was characterized by a sparse, diffuse interstitial myocarditis with little ongoing necrosis. Changes within the myocardial interstitium remote from healing necrotic foci were marked by reticular fiber thickening and disorganization, often associated with pleomorphic fibroblasts. Reticulin fiber deposition was quantitatively increased in sparsely inflamed regions of hearts from infected animals as compared to noninflamed regions from the same hearts (p < 0.005) or hearts of control animals (p < 0.001). Scanning electron microscopy revealed interstitial changes that were more extensive than indicated by routine staining with hematoxylin and eosin for Masson's trichrome. The progressive changes within the cardiac interstitium during the development of postmyocarditic cardiomyopathy suggest that direct viral infection of fibroblasts or an interaction between the interstitium and inflammatory cells and their secreted products may contribute to pathologic changes within the interstitial collagen matrix.