Occupational epidemiology and assessment of exposure.
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Biomedical subjects
Publications and source records attributed to M Goldberg.
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IgM immunoblotting and polymerase chain reaction (PCR) were evaluated for use in diagnosing congenital syphilis, and the prevalence of central nervous system (CNS) invasion by Treponema pallidum during congenital infection was examined. The results of rabbit infectivity testing (RIT) on serum and cerebrospinal fluid (CSF) of 19 infants born to mothers with untreated early syphilis were compared with results of PCR and IgM immunoblotting. Seven infants had clinical evidence of congenital syphilis supported by positive serum IgM immunoblot (7/7), PCR (6/7), and RIT (3/3). Six symptomatic infants (86%) had T. pallidum isolated from CSF by RIT; 5 of 6 RIT-positive CSF samples were positive by PCR, and 2 also were reactive by IgM immunoblot. In 12 asymptomatic infants, 5 (42%) had a reactive serum IgM immunoblot and in 4 of these IgM reactivity was the only evidence of congenital infection. CNS invasion by T. pallidum was uncommon among asymptomatic infants; only 1 (8%) was positive by CSF RIT. The excellent agreement between RIT and PCR further substantiates the use of PCR as a surrogate for RIT. Our data indicate that the diagnosis of asymptomatically infected neonates will require a comprehensive approach using assays for both specific neonatal IgM and T. pallidum DNA in serum and CSF.
The prediction of return to the workplace after Multidisciplinary Pain Center (MPC) treatment has become a major research area. To delineate the variables that predict this outcome, the authors reviewed 164 multidisciplinary variables studies. Of these, 79 addressed work as an outcome variable. Twenty-six studies attempted to identify patient variables predicting return to the workplace. These latter studies were critically inspected for eight methodological criteria: pain location, follow-up time interval, response percentage and follow-up method, return to work subcategorization, vocational movement, univariate vs. multivariate statistics, multi-colinearity and variance, and statistical treatment of dropouts. In addition, other disability studies besides those in the chronic pain area were reviewed for return to the workplace predictor variables. Of these 26 studies, only a few appeared to satisfy the criteria examined. In addition, many studies were in conflict with one another on whether a variable was predictive. The review of the nonchronic pain/disability prediction literature yielded a large number of potential predictors that related to the work area. It is unclear which variables or set of variables predict return to the workplace after MPC treatment. Chronic pain studies may be neglecting the work area as an important source of return to the workplace predictor variables.
A Bedouin family with two girls affected by severe congenital contractural arachnodactyly (CCA) is described. The girls were double second cousins. One of the girls also had ambiguous genitalia, an anomaly not generally associated with this disorder. The two children were both the product of first-cousin Bedouin parents from the same family. It is possible that both sets of parents were heterozygous for CCA; thus the infants may have been homozygous for CCA, which is usually an autosomal dominant condition. No instance of homozygous CCA has previously been reported. This family suggests genetic heterogeneity in CCA and that, in some rare families, the mode of inheritance may be autosomal recessive.
BACKGROUND: Fibrinogen-dependent cross-linking of glycoprotein (GP) IIb/IIIa on activated platelets is the final mechanism leading to platelet aggregation. Inhibition of this mechanism may result in a novel antithrombotic agent. We studied the activity of MK-383 (L-700,462), a new, nonpeptide GPIIb/IIIa antagonist, in vitro and in vivo, in man. METHODS AND RESULTS: MK-383, a nonpeptide tyrosine derivative, dose-dependently inhibited fibrinogen-dependent platelet aggregation, in vitro. Binding of 125I-labeled fibrinogen to activated platelets was prevented in a competitive manner with an IC50 of 10 +/- 4.2 nmol/L. The activity and tolerability of MK-383 were evaluated in a two-part double-blind, placebo-controlled, dose-escalation study in healthy male subjects using 1- and 4-hour intravenous infusions. Effects on ADP- and collagen-induced ex vivo platelet aggregation (APA or CPA) and template bleeding time (TBT) were evaluated. Twenty-four subjects participated in the 1-hour part. Six received placebo and 18 MK-383 in doses ranging from 0.05 to 0.40 microgram.kg-1 x min-1. MK-383 inhibited platelet aggregation and prolonged bleeding time in a dose-dependent manner. APA and CPA were totally inhibited at the end of infusion of 0.4 microgram.kg-1 x min-1 and returned to 55% and 89% of baseline, respectively, at 3 hours after infusion. TBT was prolonged at this dose from 5.0 +/- 1.3 minutes predose to 22.7 +/- 6 minutes at the end of the infusion (P < .01) and was normalized by 3 hours after infusion. In the 4-hour infusion part, 15 subjects received MK-383 (0.1 to 0.2 microgram.kg-1 x min-1), and five received placebo. Complete inhibition of ex vivo platelet aggregation was seen at 0.15 and 0.2 microgram.kg-1 x min-1. At 0.2 microgram.kg-1 x min-1, TBT was prolonged from 4.4 +/- 1.2 to 23.9 +/- 4.3 minutes at the end of infusion (P < .01) and remained slightly prolonged 3 hours after infusion (7.2 +/- 1.8 minutes). No adverse effects were observed in any of the 33 subjects receiving MK-383. CONCLUSIONS: The results from this study indicate that MK-383 appears to be well tolerated and active in man. It is the first nonpeptide GPIIb/IIIa antagonist that can be used to investigate the antithrombotic potential of this new class of antiplatelet agents.
The formation of dentin, dentinogenesis, comprises a sophisticated interplay between several factors in the tissue, cellular as well as extracellular. Dentin may be regarded as a calcified connective tissue. In this respect, as well as in its mode of formation, it is closely related to bone. Using dentinogenesis as an experimental model to study biomineralization provides several practical advantages, and the results may be extrapolated to understand similar processes in other tissues, primarily bone. After describing dentin structure and composition, this review discusses items such as the morphology of dentinogenesis; the dentinogenically active odontoblast, transport, and concentrations of mineral ions; the constituents of the dentin organic matrix; and the presumed mechanisms involved in mineral formation.
The amino acid pattern in the ascites of 79 dogs was examined. The concentration of glutamine in neoplastic ascites is significantly lower than in cardial effusions. In contrast, glutamate is significantly higher in neoplastic ascites than in cardial ascites. Using an arbitrary discrimination value of 0.28 for the glutamate/glutamine ratio, purulent or cardial ascites are easily differentiated, with a sensitivity of 100% and a specificity of 94%. The differentiation is very distinct, with no overlap between the group of patients with liver cirrhosis on the one hand and the groups of patients with purulent peritonitis, heart failure, or malignant ascites on the other hand. There was no diagnostically unsable correlation between the concentrations of the other 20 amino acids and the underlying causes of ascites formation.
Despite spectacular scientific advance and contributions to patient care, radiology stands at a frightening crossroads in its 100-year history. Economic and political changes endanger the fundamental principles of patient care, research, and teaching and threaten to dismantle the subspecialized expertise that characterizes our great academic medical institutions. In response, we should be creative and find new ways to exploit this expertise in an effort to maintain clinical and research excellence. Teleradiology can be used to improve the quality and decrease the cost of medical care at home and abroad--meeting the challenge of the 1990's. Teleradiology and other telemedical applications can benefit from the nation's investment in telecommunications infrastructure. The enabling technologies to provide teleradiology services are available and the feasibility of performing primary interpretations has been established. We offer our experience and plans as a model for diversifying and strengthening the academic radiology department of the future.
Proteoglycans (PGs) have been visualized in the predentine and dentine with cationic dyes by staining thin sections with Alcian Blue, bismuth nitrate, or using Spicer's high-iron diamine (HID) method. The precise location may be obtained by adding cationic dyes such as Cuprolinic Blue, ruthenium hexamine trichloride or cationic detergent (cetylpyridinium chloride) to the fixative. These methods induced the formation of aggregates which varied in shape and number according to the method used. Rapid freezing followed by freeze-substitution revealed an amorphous ground substance, homogeneously stained with Alcian Blue, located in the predentine between the collagen fibres. These PGs may be involved in transport and diffusion in predentine. In dentine, small granules and needle-like structures were observed along the collagen fibres. This second group of PGs differs in composition, distribution and functions from the predentine PGs. The same distribution was seen when hyaluronidase-gold labelling was used. Labelling with antibodies and autoradiography also gave evidence of two distinct groups of PGs. In predentine, as an hydrated gel, PGs seems to act as mineral inhibitors, whereas immobilized on a surface, as seen at the dentine edge, they act as nucleating agents. The interaction between PGs and phospholipids seems also to play a role in the mineralization process.
Electron-histochemical visualization of proteoglycans was carried out in the predentine and dentine of rat incisors. Using various techniques proteoglycans were seen to be located between the collagen fibres in predentine, whereas they were observed at the surface of groups of collagen fibres in dentine. The same distribution was found when electron histochemical techniques aiming to visualize phospholipids were used. This co-distribution may play role in the mineralization processes.
In vivo studies were carried out on dental tissues of rat incisor after a single injection of suramin, a drug which induces mucopolysaccharidosis-like disease. Accumulation of lysosome-like structures was seen in secretory ameloblasts and odontoblasts. In vitro studies on embryonic tooth germ buds showed similar changes when they were cultured in presence of suramin. Anti-phospholipid immunolabelling revealed a developmentally regulated temporo-spatial pattern. Radiolabeling with 3H-suramin indicated cytosolic and nuclear incorporation. The drug acting as polyanion interacted directly with predentine. 35S sulphate incorporation was impaired by the drug. Another lysosomal storage disease, the sphingolipidosis, Krabbe's disease was also investigated in human. Changes were observed in pulp cells and as a consequence in dentin. Enamel also displayed many changes. Pharmacological or genetically acquired diseases constitute models providing insights on the role played by glycosaminoglycans and phospholipids in biomineralization.
Since resistance to several oral antimicrobials useful for the treatment of pediatric urinary tract infections (UTI) is overwhelming in Argentina, an in vitro investigation was performed testing 400 isolates obtained from urines of children suffering UTI's, 200 collected in 1990 and 200 in 1991. Their susceptibility against oral antimicrobials marketed in Argentina and appropriate for the treatment of UTI was determined by the agar dilution methods. An increase of the resistance to aminopenicillin combined with beta-lactamase inhibitors and to fluoroquinolones was observed comparing the two periods. Cefpodoxime (CPD), cefixime and fluoroquinolones except norfloxacin were the sole oral antimicrobials showing in vitro activity at the 90 per cent level. Unfortunately fluoroquinolones are not yet approved for pediatric use. Consequently we realized an in vitro and in vivo pharmacokinetic study in order to determine CPD activity against E. coli isolated in UTI cases. Five children (6-10 y) showing E. coli UTI infections received 10 mg/kg/d CPD in a single oral daily dose and were treated up to 10 days, 3 had lower UTI and 2 upper UTI. All patients were clinical and bacteriologically cured. Cultures obtained up to 4 weeks after treatment were negative. CPD serum levels at 2 hours after the first dose of treatment showed a median of 2.7 mg/l (2.3-3.4 range). Bactericidal serum titers at the same time against the patients own strain and an E. coli TEM-1 hyperproducer strain (MIC 4,096 mg/l for ampicillin and 0.5 mg/l for CPD) showed a median value of 1/8 against patients strains and 1/2 against the THP strain.(ABSTRACT TRUNCATED AT 250 WORDS)
An investigation of the effects on health and social well-being of on-call shift work to cover emergencies outside working hours has been carried out by Electricité de France-Gaz de France, the French national company that supplies gas and electricity. This transversal survey compared a group of workers exposed to on-call shift work (n = 145) with a group that was not (n = 195). Each subject completed a questionnaire about the demands of his work, state of health, psychologic equilibrium using the Langner scale, and the impact of his job on social and family life. A "weekly report form," completed for 3 consecutive weeks randomly selected using a sampling plan covering the entire year to take into account seasonal variations, was subsequently filled in by 115 of the group exposed to on-call shift work and 167 of those who were not, to investigate events occurring outside working hours and sleep. The findings show that the main demands of being on-call were telephone calls, which were five times more numerous during the weeks on-call; this was accompanied by a shorter sleeping time (a mean of 6.8 hours versus 7.4 hours during a normal week) and more frequent tiredness on waking up (25.7% vs 13.2%). No particular disorder was found more frequently in the exposed group, but the psychologic equilibrium and family and social life of the workers in the on-call shift group were disturbed: some variables in the questionnaire and indices calculated from some items revealed adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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