Neurological dysfunction of the bladder in workers exposed to dimethylaminopropionitrile

Neurogenic bladder dysfunction, characterized by hesitancy, need to strain, decreased stream, and increased duration of urination, developed in 104 (63%) of 166 employees working in the manufacture of polyurethane foam. Highest rates of illness (69%) occurred in production workers, and no illness occurred in office or warehouse workers. Onset of the epidemic coincided with introduction of a catalyst, dimethylaminopropionitrile (DMAPN), and monthly case incidence rates increased as DMAPN use increased. Outbreak ceased abruptly when DMAPN use was stopped. Of eight patients who underwent neurourologic testing during recovery, seven lacked either detrusor reflex or normal sensation of bladder filling; seven had a subclinical sensory abnormality; three had prolonged sacral-evoked responses; and two of these three had limb motor neuropathies. Dimethylaminopropionitrile is unique among known neurotoxins in producing urinary symptoms more frequently than limb nerve symptoms.     

Mechanisms underlying the antidopaminergic effect of clonazepam and melatonin in striatum

Intrastriatal injection of the GABA_A antagonist, bicuculline, caused about a 75% decrease in the inhibitory effect of the central-type benzodiazepine (BZ) agonist, clonazepam or the indoleamine hormone, melatonin, on apomorphine-induced rotation in a 6-hydroxydopamine model of dopaminergic supersensitivity. Pretreatment with the peripheral-type BZ antagonist, PK 11195 (intrastriatally or intraperitoneally), also attenuated the antidopaminergic effect of these drugs but with much less potency than bicuculline. However, the combination of both bicuculline and PK 11195, injected directly into the striatum, completely blocked the antidopaminergic action of clonazepam or melatonin. These results indicate that the antidopaminergic action of clonazepam and melatonin in the striatum involves two distinct mechanisms: (1) a predominant GABAergic activation via the BZ/GABA_A receptor complex, and (2) a secondary mechanism linked to a PK 11195- sensitive BZ receptor pathway. Recent studies indicate that PK 11195 blocks BZ-induced inhibition of the adenylyl cyclase-cyclic AMP pathway in the striatum. Since cyclic AMP has been implicated in the rotational behaviour of 6-hydroxydopamine-lesioned animals, it is possible that the antidopaminergic action of clonazepam and melatonin also involves suppression of this second messenger. All rights reserved.     

Evaluation of the Kirby-Bauer disc diffusion test as a screening test for high-level aminoglycoside resistance in enterococci

The Kirby-Bauer disc diffusion test was evaluated as a test to detect high-level aminoglycoside (streptomycin, kanamycin, tobramycin, and gentamicin) resistance in isolates of enterococci. The authors found that high-level resistance could not be predicted accurately with the diffusion test.     

Clinical laboratory evaluation of a urine screening device

A study was conducted to compare the Bac-T-Screen Bacterial Detection Device for Urines (BDD; Marion Laboratories, Kansas City, Mo.) with urine Gram stain as a screen for bacteriuria. We analyzed 631 urine samples with the BDD and compared the results to urine Gram stains and quantitative cultures. A total of 90 (14%) specimens could not be analyzed with the BDD due to interfering pigments (67 specimens) or clogging of the filter (23 specimens). Of the 541 specimens that were analyzed, the BDD correctly identified 67 (88.2%) of the 76 specimens with greater than or equal to 10(5) CFU/ml but only 294 (63.2%) of the 465 specimens with less than 10(5) CFU/ml. The majority of the false negative specimens had either gram-positive organisms or yeasts. The predictive value of a negative BDD reading was 97.0%. The urine Gram stain correctly identified 92.1% of all positive cultures and 77.8% of all negative cultures. The predictive value of a negative urine Gram stain was 98.4%. In summary, the BDD compares favorably with the urine Gram stain as a screen for bacteriologically negative urine specimens.     

Comparison of a highly automated 5-h susceptibility testing system, the Cobas-Bact, with two reference methods: Kirby-Bauer disk diffusion and broth microdilution.

The results of susceptibility tests performed with the Cobas-Bact system were compared with those of the Kirby-Bauer disk diffusion and the broth microdilution methods. The evaluation included tests with 24 antibiotics against 250 isolates of the family Enterobacteriaceae and 13 antibiotics against 100 gram-positive cocci. Complete agreements between the Cobas-Bact and Kirby-Bauer methods were 82.8 and 84.5% for gram-positive cocci and gram-negative bacilli, respectively. Agreements between the Cobas-Bact and broth microdilution methods were 76.7% for gram-positive cocci and 84.8% for gram-negative bacilli. Complete agreements between the Kirby-Bauer and broth microdilution methods were 87.0% for gram-positive cocci and 92.2% for gram-negative bacilli. Despite generally satisfactory results with most organism-antibiotic combinations tested, additional modifications of the Cobas-Bact system are required to reduce the number of major and very major discrepancies, as well as to permit testing of Pseudomonas spp. and other gram-negative nonfermentative bacilli.     

Sequencing of the alpha-synuclein gene in a large series of cases of familial Parkinson's disease fails to reveal any further mutations. The European Consortium on Genetic Susceptibility in Parkinson's Disease (GSPD)

A mutation in exon 4 of the human alpha-synuclein gene was reported recently in four families with autosomal dominant Parkinson's disease (PD). In order to examine whether mutations in this exon or elsewhere in the gene are common in familial PD, all seven exons of the alpha- synuclein gene were amplified by PCR from index cases of 30 European and American Caucasian kindreds affected with autosomal dominant PD. Each product was sequenced directly and examined for mutations in the open reading frame. No mutations were found in any of the samples examined. We conclude that the A53T change described in the alpha- synuclein gene is a rare cause of PD or may even be a rare variant. Mutations in the regulatory or intronic regions of the gene were not excluded by this study.      

Evaluation of microparticle enzyme immunoassays for immunoglobulins G and M to rubella virus and Toxoplasma gondii on the Abbott IMx automated analyzer.

The ability of the Abbott IMx automated analyzer to detect immunoglobulin G (IgG) and IgM antibodies to rubella virus and to Toxoplasma gondii was compared with the abilities of RUBAZYME, RUBAZYME-M, ABBOTT TOXO-G enzyme immunoassay, and ABBOTT TOXO-M enzyme immunoassay, respectively. Specimens that produced discordant results were evaluated by RUBACELL II, Behring Enzygnost-Rubella enzyme-linked immunosorbent assay, Behring Enzygnost Toxoplasmosis/IgG, and bioMerieux Toxo-ISAGA (immunosorbent agglutination assay), respectively. After resolution of discordant results, IMx Rubella IgG, IMx Rubella IgM, IMx Toxo IgG, and IMx Toxo IgM antibody assays had sensitivities of 99.9, 100, 98.0, and 100%; specificities of 98.9, 99.0, 97.5, and 98.7%; and accuracies of 99.8, 99.3, 97.8, and 98.8%, respectively.     

Detection of two forms of GP330. Their role in Heymann nephritis.

Heymann nephritis is characterized by glomerular immune deposits that contain a glycoprotein called gp330. The deposits are believed to result from shedding of immune complexes formed on podocytes. Complexes are also shed from proximal tubule cells, when antibodies combine with gp330 on the cell surface. We performed the present study to investigate what portion of the gp330 molecule is shed, using a rabbit antiserum against a peptide deduced to be in the cytoplasmic domain of gp330, as well as a rabbit antiserum and two monoclonal antibodies that recognize extracellular epitopes of gp330. The anti-cytoplasmic peptide antiserum precipitated from Fx1A (a crude renal cortical membrane preparation), a protein with a mass of about 440 kd that was reactive with two monoclonal anti-gp330 antibodies. (In our experiments, the protein called gp330 generally has a mass estimated to be about 440 kd.) The anti-cytoplasmic peptide antiserum also reacted with a truncated gp330 protein produced in transfected COS cells. Immunohistochemical studies showed that all the antibodies recognized the same group of epithelial cells. However, as seen in immunoultrastructural studies of proximal tubules, the anti-cytoplasmic peptide antiserum reacted only with components at the base of microvilli, whereas the anti-gp330 ectodomain antibodies identified material not only at the base, but over the surface of microvilli as well. In rats with Heymann nephritis, glomerular deposits and material shed into tubule lumens reacted with antibodies against extracellular epitopes of gp330, but not with the anti-cytoplasmic peptide antiserum. We propose that there are two forms of gp330 on the cell surface of proximal renal tubules. One form is restricted to coated pit regions at the base of microvilli and has a cytoplasmic domain containing a sequence deduced from a partial complementary DNA encoding gp330. The other form is present over microvilli (and possibly at the base of microvilli as well) and lacks the cytoplasmic domain deduced from the complementary DNA. The complexes that are shed in Heymann nephritis contain either a portion of gp330 cleaved from the full-length molecule or a form of gp330 that lacks the cytoplasmic domain.