Biomedical subjects
D Barr
Publications and source records attributed to D Barr.
Investigation of systemic lupus erythematosus in Nogales, Arizona.
In 1996, a citizens group in Nogales, Arizona, reported to the Arizona Department of Health their concerns about a possible excess prevalence of systemic lupus erythematosus (SLE) due to exposure to environmental contamination in the area. The authors conducted a two-phase study in which the objectives of phase I were to identify potential SLE cases and to determine the prevalence of SLE and the objectives of phase II were to identify potential risk factors associated with the development of SLE and to evaluate the possible association between SLE and environmental exposure to pesticides and inorganic compounds. Participants included 20 confirmed cases and 36 controls. The authors found the prevalence of SLE to be 103 cases per 100,000 population (95 percent confidence interval: 56, 149), two to seven times higher than the prevalence in the US population. They detected elevated levels of 1,1-dichloro-2,2-bis-(p-chorophenyl)ethylene and organophosphate metabolites among cases and controls. In both, levels were higher than the reference mean for the US population. The authors found no statistical association between elevated levels of pesticides and disease status. Their results show that the prevalence of SLE in Nogales is higher than the reported prevalence in the US population and that both cases and controls had past exposure to chlorinated pesticides and have ongoing exposure to organophosphates.
Too smart for our own good.
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Isolated sixth nerve palsy: an uncommon presenting sign of multiple sclerosis.
We describe three patients in whom an isolated sixth nerve palsy was the only clinical symptom or sign of multiple sclerosis (MS). Data were collected prospectively over 6 years on these three patients, who showed no other signs of brainstem dysfunction or prior symptoms; in addition. Retrospective analysis of all patients with MS and all patients with sixth nerve palsy referred to a neuro-ophthalmology service between 1982 and 1998 showed isolated sixth nerve palsy to be the presenting sign of MS in only 0.5% of these patients. MS was the cause of isolated sixth nerve palsy in 0.8% of all patients and in 1.6% of those aged 18-50 years. Although it has been previously suggested that sixth nerve palsy is a not uncommon presenting sign of MS, our results suggest it is rare.
Performance measures for guidelines on preventing opportunistic infections in patients infected with human immunodeficiency virus.
This article serves as a complement to the 1999 US Public Health Service/Infectious Diseases Society of America guidelines on the prevention of opportunistic infections in persons infected with HIV, published in this issue of Clinical Infectious Diseases [1]. A number of performance measures to assess compliance with the guidelines and to aid in their implementation are proposed.
Synkinesis following diabetic third nerve palsy.
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Meeting the healthcare needs of refugees and asylum seekers.
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Assessing prenatal hepatitis B screening in Illinois with an inexpensive study design adaptable to other jurisdictions.
OBJECTIVES: This study estimated, using an economical survey design adaptable to other jurisdictions, the proportion of birth admissions in Illinois hospitals in which mothers were not screened for hepatitis B surface antigen prior to delivery. It also identified factors associated with lack of screening. METHODS: Based on a cluster sampling design, 1372 birth records were sampled, and data were abstracted by local personnel at 56 hospitals. Selected data elements were reabstracted on a subsample to evaluate recording errors. RESULTS: Reabstracted data demonstrated 95% agreement among reviewers. Hepatitis B surface antigen screening was documented for 90.7% of mothers; 11% of responding hospitals accounted for 45% of nonscreened mothers. Risk factors for not being screened included no prenatal care, Medicaid or no insurance, and delivery at a hospital lacking a written hepatitis B surface antigen policy. CONCLUSIONS: In Illinois, prenatal hepatitis B surface antigen screening rates were high and similar to those in other states. Births without screening or transferred information clustered in a few hospitals. The methods used here can economically identify underscreened populations by sampling a large number of hospitals within designated areas.
Arachnoid cyst of the cavernous sinus resulting in third nerve palsy.
A 67-year-old man exhibited long-standing left third nerve palsy. Magnetic resonance imaging revealed a cystic lesion in the left cavernous sinus with signal characteristics typical of arachnoid cyst. Intradural cavernous sinus arachnoid cyst has not reported previously. Pathogenetic mechanisms are discussed.
Recombinant human tumor necrosis factor receptor Fc fusion protein therapy in kidney transplant recipients undergoing OKT3 induction therapy.
BACKGROUND: Initial doses of OKT3 are associated with a cytokine-induced acute clinical syndrome (ACS). This study assessed the safety of a recombinant human tumor necrosis factor receptor fusion protein (TNFR:Fc) given to minimize OKT3-ACS symptoms in renal allograft recipients undergoing induction therapy. METHODS: Sixteen patients were randomized into treatment or control groups. Treated patients received TNFR:Fc 1 hr before OKT3 on days 0 and 3. Patients were monitored after transplant for OKT3-ACS symptoms. Levels of cytokines, serum creatinine, and C-reactive protein were followed. RESULTS: Patients receiving TNFR:Fc had lower OKT3-ACS symptoms as measured by a scoring system. There was a higher incidence of infection in treated patients (10/12) compared to controls (1/4) in the 3 months after transplant, but the etiology of this difference was unclear. There were no significant differences in cytokine profiles. CONCLUSIONS: TNFR:Fc is well tolerated by renal transplant patients receiving OKT3 induction therapy and modestly decreases the symptoms associated with OKT3-ACS.
Monocular band optic atrophy.
Band or "bow tie" optic atrophy is characterized by well-described ophthalmoscopic findings in the optic nerve and nerve fiber layer and homonymous hemianopia. It is typically associated with compressive lesions of the pregeniculate postchiasmal visual pathway or, less commonly, congenital malformations affecting the postgeniculate radiations or cortex. A unique case with band optic atrophy is described because of the unilateral visual defect. The optic atrophy is strictly unilateral and without an obvious structural lesion that could explain the optic disc damage. However, incidental cerebral gray matter cortical heterotopia may mark a congenital insult that contributed to both of these abnormal findings.
Induction immunosuppressive therapy is associated with a low rejection rate after liver transplantation.
Despite advances in immunosuppression, allograft rejection occurs frequently after liver transplantation. The use of induction therapy with cytolytic antibodies may decrease the frequency of rejection in liver transplant recipients, but may also increase the rate of cytomegalovirus (CMV) infection. It has been our center's strategy to use induction therapy in our liver transplant recipients. To determine the outcome of our strategy, we retrospectively reviewed all liver transplants performed in the first 5 yr of our liver transplant program. The frequency of acute rejection in the first year after liver transplantation was only 34% in patients who received induction therapy. The type of induction therapy antibody did not affect the rejection rate. Clinically significant CMV infection (requiring treatment) occurred in 22% of patients. These results suggest that use of induction therapy with cytolytic antibodies does not lead to a high incidence of CMV infection and decreases the incidence of rejection after liver transplantation.
Oxidation of 1,2,4,5-tetramethoxybenzene by lignin peroxidase of Phanerochaete chrysosporium.
We have reinvestigated the lignin peroxidase-catalyzed oxidation of 1,2,4,5-tetramethoxybenzene (TMB) by using presteady-state and steady-state kinetic methods. Our presteady-state kinetic results show that the reaction of compound I with TMB obeyed second order kinetics with a rate constant of 1.1 x 10(7) M-1s-1. The reaction of compound II with TMB exhibits a hyperbolic concentration dependence with a Kd of 16 microM and K = 24 s-1. The stoichiometry of TMB oxidation during steady state is two TMB cation radicals formed per H2O2 consumed. These results clearly show that TMB is a good substrate for both compounds I and II of lignin peroxidase.
Ocular tumoral calcinosis. A clinicopathologic study.
Tumoral calcinosis is a rare systemic disorder characterized by para-articular ectopic soft-tissue calcification. This case report describes the ophthalmic features (palpebral conjunctival calcific nodules, the white limbal girdle of Vogt, disc drusen, and angioid streaks) in a 38-year-old Asian woman who had tumoral calcinosis associated with hyperphosphatemia. A morphologic study of the calcified nodules on the palpebral conjunctiva disclosed deposition of hydroxyapatite crystals in an extracellular matrix (deposit) containing alcianophilic mucopolysaccharides. Excision of the eyelid nodules was not followed by recurrence.
The natural history of untreated focal allograft rejection in liver transplant recipients.
Focal rejection involves less than 20% of portal tracts in liver allograft biopsy results. The clinical significance of "focal" rejection on protocol liver biopsy results is unknown. The purpose of this study was to prospectively determine the incidence of clinically significant rejection in patients with focal rejection after orthotopic liver transplantation. Biopsy specimens from 165 consecutive transplantations in 149 patients were analyzed. After protocol biopsy specimens were obtained, patients with focal or mild rejection were observed. Fifty of 583 (8.6%) protocol biopsy results in 41 patients showed focal or mild rejection. None were treated on the basis of this histological finding. Six patients subsequently developed abnormal liver function tests and required treatment with additional immunosuppression. We conclude that focal or mild rejection is a relatively common finding on protocol liver biopsy results and only rarely progresses to a clinically significant problem. Patients with this finding can safely be observed without treatment.
Elimination of hepatitis C virus RNA in infected human hepatocytes by adenovirus-mediated expression of ribozymes.
Hepatitis C virus (HCV), a positive-strand RNA virus, is the major infectious agent responsible for causing chronic hepatitis. Currently, there is no vaccine for HCV infection, and the only therapy for chronic hepatitis C is largely ineffective. To investigate new genetic approaches to the management of HCV infection, six hammerhead ribozymes directed against a conserved region of the plus strand and minus strand of the HCV genome were isolated from a ribozyme library, characterized, and expressed from recombinant adenovirus vectors. The expressed ribozymes individually or in combination were efficient at reducing or eliminating the respective plus- or minus-strand HCV RNAs expressed in cultured cells and from primary human hepatocytes obtained from chronic HCV-infected patients. This study demonstrates the potential utility of ribozyme therapy as a strategy for the treatment of hepatitis C virus infection.
On people's understanding of the diagnostic implications of probabilistic data.
Two lines of prior research into the conditions under which people seek information are examined in light of two statistical definitions of diagnosticity. Five experiments are reported. In two, subjects selected information in order to test a hypothesis. In the remaining three, they selected information in order to convince someone else of the truth of a known hypothesis. A total of 567 university students served as subjects. The two primary conclusions were as follows: (1) When the task is highly structured by the environment, subjects select information diagnostically, and (2) when the task is less structured, so that subjects must seek relevant information not manifest, they select information pseudodiagnostically. Possible relations to other laboratory inference tasks and to clinical judgment are discussed.
Identification of platelet-derived growth factor A and B chains in human renal vascular rejection.
Platelet-derived growth factor (PDGF) exists as a dimer composed of two homologous but distinct peptides termed PDGF-A and -B chains, and may exist as AA, AB, and BB isoforms. The PDGF-B chain has been implicated as a mediator of renal vascular rejection by virtue of up-regulated expression of its receptor, PDGF beta-receptor, in affected arteries. A role for PDGF-A chain in mediating intimal proliferation has been suggested in human atherosclerosis (Rekhter MD, Gordon D: Does platelet-derived growth factor-A chain stimulate proliferation of arterial mesenchymal cells in human atherosclerotic plaques? Circ Res 1994, 75:410), but no studies of this molecule in human renal allograft injury have been reported to date. We used two polyclonal antisera to detect expression of PDGF-A chain and one monoclonal antibody to detect PDGF-B chain by immunohistochemistry in fixed, paraffin-embedded tissue from 1) normal adult kidneys, 2) a series of renal transplant biopsies chosen to emphasize features of vascular rejection, and 3) allograft nephrectomies. Immunohistochemistry was correlated with in situ hybridization on adjacent, formalin fixed tissue sections from nephrectomies utilizing riboprobes made from PDGF-A and -B chain cDNA. PDGF-A chain is widely expressed by medial smooth muscle cells of normal and rejecting renal arterial vessels of all sizes by immunohistochemistry and in situ hybridization. PDGF-A chain is also expressed by a population of smooth muscle cells (shown by double immunolabeling with an antibody to alpha-smooth muscle actin) comprising the intima in chronic vascular rejection. In arteries demonstrating acute rejection, up-regulated expression of PDGF-A chain by endothelial cells was detected by both immunohistochemistry and in situ hybridization. In contrast, PDGF-B chain was identified principally in infiltrating monocytes within the rejecting arteries, similar to its localization in infiltrating monocytes in human atherosclerosis. Although less prominent than the case for PDGF-A chain, PDGF-B chain also was present in medial and intimal smooth muscle cells in both rejecting and nonrejecting renal arteries. PDGF-A and -B chains have now been localized at both the mRNA and protein levels to the intimal proliferative lesions of vascular rejection. These peptides, which are known stimuli for smooth muscle cell migration and proliferation in experimental vascular injury, may have similar stimulatory effects on smooth muscle cells in an autocrine and/or paracrine manner to promote further intimal expansion and lesion progression in this form of human vasculopathy.