Latex allergen contents of rubber gloves packaged in sterile medical kits and trays.
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Allergens↗
Biomedical subjects
R T Jones
Publications and source records attributed to R T Jones.
Inhalation challenge testing of latex-sensitive health care workers and the effectiveness of laminar flow HEPA-filtered helmets in reducing rhinoconjunctival and asthmatic reactions.
BACKGROUND: There are few data relating latex aeroallergen concentrations to biologic responses in latex-sensitized persons. OBJECTIVES: We sought to investigate acceptable latex aeroallergen concentrations below which latex-sensitive health care workers do not experience symptoms and to study the effect of high-efficiency particle arrest (HEPA)-filtered laminar flow helmets in preventing latex-induced symptoms. METHODS: Under challenge chamber conditions, latex-sensitive health care workers underwent 7 sequential inhalation challenge tests by donning and discarding either vinyl gloves (challenge 1), low latex-allergen powder-free gloves (challenge 2), or high latex-allergen powdered gloves (challenges 3 to 7) for up to 1 hour. Volunteers wore a laminar flow helmet during all challenges; HEPA filters in the helmet were in place only during challenges 3 and 4. Flow-volume loops, symptom scores, and latex aeroallergen concentrations were measured before and during each test. RESULTS: At 60 minutes, latex aeroallergen concentrations during challenges 3 to 7 (mean, 7600 ng/m3; range, 93 to 54,000 ng/m3 ) were significantly higher than during challenges 1 or 2 (mean, 65 ng/m3; range, nondetectable to 100 ng/m3 ) (P <.001). During challenges 5 and 6, mean maximum percent falls in FEV1 (-16% and -11%, respectively) were significantly greater compared with those measured during challenges 3 and 4 (-3% and -1%, respectively) (P =.03). Mean maximum change from baseline symptom scores during challenges 5 and 6 was significantly higher than that during challenges 3 and 4 (P =.006). During challenges with high latex-allergen gloves, 4 volunteers had reproducible FEV1 falls of 20% or greater at cumulative inhaled latex aeroallergen doses ranging from less than 100 ng to 1500 ng. CONCLUSION: The laminar flow helmets were effective in reducing latex-induced symptoms. Only 1 volunteer exhibited a fall in FEV1 of 20% or greater after a cumulative inhaled latex aeroallergen dose of less than 100 ng, and no volunteer showed a decline in FEV1 after exposure to powder-free low allergen gloves.
Adult↗
Prevalence and geographic origin of pigs with serological evidence of infection with Leptospira interrogans serovar pomona slaughtered in abattoirs in Victoria, Australia.
A set of 10,440 sera was collected from pigs slaughtered at Victorian abattoirs. These sera were subjected to the microscopic agglutination test for antibodies to Leptospira interrogans serovar pomona. Identification of the herd of origin was possible for 6511 pigs, and these were derived from 167 herds in Victoria (84% of sera), from 32 herds in New South Wales (8% of sera) and 29 herds in South Australia (8% of sera). The overall prevalence of titres of 512 and above was 3.7%. This was higher (5.3%) among pigs for which the property of origin was unknown than among pigs with identified properties of origin. Among the latter the prevalence was 2.7% (Victoria 0.6%, New South Wales 1.3%, South Australia 25.2%.) Most of the pigs with unknown properties of origin were derived from market groups and were probably typically from smaller herds. Within Victoria a comparison of results with the known pig populations of the 12 statistical divisions indicated that infection was spread throughout the State. Of the 228 identified herds of origin sampled, 32 (14%) had at least one pig with a high titre. However, this may underestimate the proportion of infected herds, as in many cases only a few serum samples were obtained. Of 73 herds from which 25 or more serum samples were obtained, serological evidence of infection was obtained in 18 herds (25%).
Abattoirs↗
Vascular endothelial growth factor and nitric oxide synthase expression in human lung cancer and the relation to p53.
Vascular endothelial growth factor (VEGF) expression and mutations of cancer-related genes increase with cancer progression. This correlation suggests the hypothesis that oncogenes and tumour suppressors regulate VEGF, and a significant correlation between p53 alteration and increased VEGF expression in human lung cancer was reported recently. To further examine this hypothesis, we analysed VEGF protein expression and mutations in p53 and K-ras in 27 non-small-cell lung cancers (NSCLC): 16 squamous cell, six adenocarcinomas, one large cell, two carcinoids and two undifferentiated tumours. VEGF was expressed in 50% of the squamous cell carcinomas (SCC) and carcinoids but none of the others. p53 mutations occurred in 14 tumours (52%), and K-ras mutations were found in two adenocarcinomas and one SCC; there was no correlation between the mutations and VEGF expression. As nitric oxide also regulates angiogenesis, we examined NOS expression in NSCLC. The Ca2+-dependent NOS activity, which indicates NOS1 and NOS3 expression, was significantly reduced in lung carcinomas compared with adjacent non-tumour tissue (P < 0.004). Although the Ca2+-independent NOS activity, which indicates NOS2 expression, was low or undetectable in non-tumour tissues and most carcinomas, significant activity occurred in three SCC. In summary, our data do not show a direct regulation of VEGF by p53 in NSCLC. Finally, we did not find the up-regulation of NOS isoforms during NSCLC progression that has been suggested for gynaecological and breast cancers.
Carcinoma, Small Cell↗
Anaphylaxis in a milk-allergic child following ingestion of lemon sorbet containing trace quantities of milk.
Although allergic persons can react to foods containing trace quantities of unlabeled or unintended food allergens, there are few data available on the quantities of these allergens required to evoke allergic symptoms. We report a milk-allergic 3-year-old boy who experienced throat itching, facial angioedema, and vomiting within 20 min of ingesting 4 to 6 oz (ca. 113.4 to 170.1 g) of lemon sorbet. Subsequent analysis of two sorbet samples provided by the parents and a third sample purchased locally by the investigators revealed trace quantities of milk allergens, whey protein (8.8 micrograms/ml), or lactose (200 ppm). The quantity of whey protein ingested was estimated to be 120 to 180 micrograms (equivalent to 23 to 24 microliters of milk). All three sorbet samples had been manufactured in the same plant within a 4-month period; the equipment used to produce and package the sorbet was also used to produce and package ice cream. No milk allergen or whey protein was detected in 38 other marketplace sorbet samples submitted by the manufacturer for testing. We concluded that trace quantities of whey proteins (< 200 micrograms) can elicit systemic reactions in exquisitely milk-allergic individuals. Such individuals should avoid eating frozen desserts prepared using equipment also used for producing or packaging ice cream, unless manufacturers can demonstrate unequivocally that their cleaning practices are sufficient to prevent milk contamination. Adequate tests are not currently available to food manufacturers but are under development.
Allergens↗
Hemoglobin Old Dominion/Burton-upon-Trent, beta 143 (H21) His-->Tyr, codon 143 CAC-->TAC--a variant with altered oxygen affinity that compromises measurement of glycated hemoglobin in diabetes mellitus: structure, function, and DNA sequence.
OBJECTIVE: To determine the nature and characteristics of a unique hemoglobin variant that causes a spurious increase in glycated hemoglobin (HbA1c). MATERIAL AND METHODS: Blood specimens from four unrelated persons with this hemoglobin variant were examined by conventional laboratory methods, including electrophoresis, high-performance ion-exchange chromatography, and isoelectric focusing; by amino acid sequence analysis, polymerase chain reaction-based DNA sequence analysis, and electrospray ionization mass spectrometry, to establish the molecular structure; and by studies of oxygen affinity under varied conditions, to define the functional characteristics of the hemoglobin variant. RESULTS: The unique hemoglobin variant observed in these four cases is due to the mutation CAC-->TAC, at beta-globin gene codon 143, corresponding to beta 143 (H21) His-->Tyr. This amino acid substitution affects an important 2,3-diphosphoglycerate binding site and slightly increases the oxygen affinity of the hemoglobin variant. CONCLUSION: A hitherto unrecognized hemoglobin variant, encountered in four unrelated persons of Irish or Scots-Irish ancestry, hemoglobin Old Dominion/Burton-upon-Trent, beta 143 (H21) His-->Tyr, has now been characterized at the molecular, structural, and functional levels. Although it is associated with a slight increase in oxygen affinity, it is without hematologic effect, and its only clinical significance is that it coelutes with HbA1c on ion-exchange chromatography and thereby causes a spurious increase in HbA1c and compromises the use of this analyte to monitor the treatment of diabetes mellitus.
Adult↗
p21waf1/cip1 and transforming growth factor beta 1 protein expression correlate with survival in non-small cell lung cancer.
p21waf1/cip1 encodes a cyclin-dependent kinase inhibitor that is transcriptionally activated by the p53 tumor suppressor gene, transforming growth factor beta 1 (TGF-beta 1), AP2, and other pathways. Because p21waf1/cip1, p53, and TGF-beta 1 all regulate apoptosis and the cell cycle, we tested the hypothesis that their relative protein levels would correlate with biological features including the survival of non-small cell lung cancer (NSCLC) patients. We conducted an immunohistochemical analysis of p21waf1/cip1 and TGF-beta 1 and identified four patient groups with distinct survival outcomes. Concordant p21waf1/cip1 and TGF-beta 1 expression (i.e., either high p21waf1/cip1 and high TGF-beta 1 expression or low p21waf1/cip1 and low TGF-beta 1 expression) predicted 70% disease-free survival at 2000 days of follow-up. Discordant p21waf1/cip1 and TGF-beta 1 expression (i.e., either high p21waf1/cip1 and low TGF-beta 1 expression or low p21waf1/cip1 and high TGF-beta 1 expression) predicted 35% disease-free survival (P = 0.0003; log-rank test). These survival relationships were not attributable to differences in grade, stage, or p53 status. Although current models do not fully explain these complex interactions, most of these data fit a paradigm whereby TGF-beta 1 regulation determines NSCLC survival. In addition to the survival correlation, we found that high p21waf1/cip1 protein expression correlated with high tumor grade (P = 0.014). There is little evidence that p21waf1/cip1 protein levels accurately predict p53 mutation status in NSCLC; specifically, 20 of 48 (42%) tumors with p53 mutations contained high levels of p21waf1/cip1 protein. These findings indicate that p21waf1/cip1 immunohistochemical analysis may provide useful information concerning the biological properties of NSCLC.
Carcinoma, Non-Small-Cell Lung↗
Allosteric intermediates indicate R2 is the liganded hemoglobin end state.
Hemoglobin has been a long-standing paradigm for understanding protein allostery. Here, the x-ray structures of two chemically crosslinked, fully liganded hemoglobins, alpha2beta82CA82beta and alpha2beta82ND82beta, are described at 2.3 A and 2.6 A resolution, respectively. Strikingly, these crosslinked hemoglobins assume intermediate conformations that lie between those of R and the controversial liganded hemoglobin state R2 rather than between R and T. Thus, these structures support only a T left and right arrow R left and right arrow R2 allosteric pathway and underscore the physiological importance of the R2 conformation.
Allosteric Regulation↗
Buprenorphine and naloxone interactions in methadone maintenance patients.
Buprenorphine is undergoing clinical trials for the treatment of opiate addiction. Although the abuse liability of sublingual buprenorphine is low, reports of intravenous abuse have appeared. This study describes the physiologic and subjective effects of intravenously administered buprenorphine and naloxone given alone and in combination to methadone-maintained patients (40-60 mg/day). On four separate occasions at least 1 day apart, 6 subjects were administered either 0.2 mg buprenorphine, 0.1 mg naloxone, 0.2 mg buprenorphine and 0.1 mg naloxone in combination, or placebo. One male subject quit the experiment after three sessions because of excessive opiate withdrawal. Buprenorphine produced no significant physiologic or subjective effects. Naloxone produced marked opiate withdrawal symptoms. Buprenorphine in combination with naloxone produced characteristic physiologic and subjective opiate antagonist-like symptoms and signs. The parenteral abuse potential of the buprenorphine and naloxone combination is discussed.
Adult↗
Occupational allergic rhinoconjunctivitis and asthma due to fennel seed.
BACKGROUND: A patient with complaints of rhinitis and asthma occurring at work presented for consultation. OBJECTIVES: To evaluate the role of the foods and spices with which he worked, in the causation of his complaints, and to evaluate his immune reactivity to these materials. METHODS: Allergy skin testing and in vitro RAST assays were carried out. After demonstrating specific reactivity to fennel, SDS-PAGE electrophoreses was carried out. RESULTS: Positive skin tests to grass, ragweed, and freshly prepared fennel seed were found. Serum IgE antibodies to fennel were quite high. Immunoblotting studies showed reactions to two components in fennel extract as well as to components in mugwort, paprika, short ragweed and black pepper. CONCLUSION: This case of occupational rhinitis and asthma in an atopic individual involves sensitivity to unique allergens in fennel, with molecular weights of 67 to 75 KD.
Adult↗
Bioavailability of sublingual buprenorphine.
Buprenorphine administered sublingually is a promising treatment for opiate dependence. Utilizing a new, sensitive, and specific gas chromatographic electron-capture detector assay, the absolute bioavailability of sublingual buprenorphine was determined in six healthy volunteers by comparing plasma concentrations after 3- and 5-minute exposures to 2 mg sublingual and 1 mg intravenous buprenorphine. The amount of unabsorbed buprenorphine in saliva was measured after 2-, 4-, and 10-minute exposures to 2 mg sublingual buprenorphine in 12 participants. Pharmacokinetic parameters were analyzed by analysis of variance; bioequivalence was evaluated by the Schuirmann two-sided test. The 3- and 5-minute sublingual exposures each allowed 29 +/- 10% bioavailability (area under the plasma concentration-time curve unextrapolated) and were bioequivalent. Buprenorphine recovered from saliva after 2-, 4-, and 10-minute exposures was, on average, 52% to 55% of dose. Increased saliva pH was correlated with decreased recovery from saliva. Study results indicate that bioavailability of sublingual buprenorphine is approximately 30%. Sublingual exposure times between 3 and 5 minutes produce equivalent results. Buprenorphine remaining in saliva causes an almost twofold overestimation of bioavailability.
Administration, Sublingual↗
Hb T-Cambodia, a beta chain variant with the mutations of Hb E and Hb D-Punjab, confirmed by DNA analysis.
Hemoglobin variants with two amino acid substitutions affecting one globin chain are relatively rare. Hb T-Cambodia, a doubly substituted beta-globin variant, was characterized previously by amino acid sequencing as having sequence alterations in beta 26 (beta 8)Glu-->Lys and beta 121(GH4) Glu-->Gln (1). It is a variant that migrates cathodic to Hb A2 on alkaline electrophoresis and with Hb A on acid citrate agar electrophoresis. We report here the mutations of Hb T-Cambodia at the nucleotide level using DNA sequencing, in beta-globin gene codon 121 (GAA-->CAA) and in codon 26 (GAG-->AAG). These are the mutations of Hb D-Punjab and Hb E, respectively.
Adult↗
Hb Seal Rock [(alpha 2)142 term-->Glu, codon 142 TAA-->GAA]: an extended alpha chain variant associated with anemia, microcytosis, and alpha-thalassemia-2 (-3.7 Kb).
Hb Seal Rock was first reported in a young African-American women and her 2-year-old daughter (1). It is an extended alpha chain variant which, like Hb Constant Spring, is present in small quantity and is expressed as an alpha-thalassemia. The mutation, TAA-->GAA affects codon 142 of the alpha 2 gene. In this family, the index case was a compound heterozygote for Hb Seal Rock trait and for alpha-thalassemia trait (-3.7 kb). Her hematologic expression was similar to mild Hb H disease, presumably because the Seal Rock mutation affects the alpha 2 gene that is normally responsible for approximately 70% of alpha-globin synthesis. Her daughter had only Hb Seal Rock trait, but was phenotypically alpha-thalassemia-2 trait due to the expression of the Seal Rock mutation on one of her alpha 2-globin genes, the other three alpha-globin genes being unaffected.
Adult↗
Measurement properties of quantitative urine benzoylecgonine in clinical trials research.
Psychometric data are presented which examine the validity of using the concentration of benzoylecgonine in urine, a major metabolite of cocaine, as a measure of drug use, in studies of drug abuse treatments. In such research the standard biological indicator of drug use is usually a qualitative urine drug test, which merely indicates the presence or absence of a drug or its metabolite. A quantitative (i.e. continuous) outcome measure, such as the concentration of a drug or its metabolite in a biological fluid, has substantially more statistical power than a dichotomous measure and should, therefore, prove a more sensitive measure of drug use when viewed from a measurement perspective. Data from two placebo-controlled clinical trials of fluoxetine as an adjunct to treatment for cocaine abuse are analyzed to address this issue. Results indicate that urine benzoylecgonine level is closely related to self-reports of drug use and is independent of levels of anxiety, depression and hopelessness.
Adult↗
Subnanogram-concentration measurement of buprenorphine in human plasma by electron-capture capillary gas chromatography: application to pharmacokinetics of sublingual buprenorphine.
We describe a sensitive and specific method for the measurement of buprenorphine in human plasma. The method involves a structural analog as an internal calibrator, careful control of pH during sample extraction to maximize drug recovery, and back-extraction into acid followed by reextraction to eliminate endogenous interferences. After evaporation, sample residues are derivatized with heptafluorobutyric anhydride and analyzed by separation on a fused-silica polymethylsiloxane capillary column and electron-capture detection. Calibration curves were linear in the ranges 0.1-2.0 micrograms/L and 2.0-20 micrograms/L, with within-run CVs of 9.7% at 0.1 microgram/L to 5.0% at 20 micrograms/L, and total CVs of 15.9% at 0.1 microgram/L to 6.5% at 10 micrograms/L. The limit of quantification was 0.1 microgram/L. The method was utilized in studies to determine the absolute bioavailability of sublingual doses of 2 mg of buprenorphine in 1 mL of 300 mL/L ethanol and the bioequivalence of sublingual 8-mg tablet and 300 mL/L ethanol solution formulations.
Administration, Sublingual↗
Pharmacokinetics of cocaine: considerations when assessing cocaine use by urinalysis.
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Cocaine↗
Patients' understanding of consent form should be checked before participation in trial.
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Clinical Trials as Topic↗
A doubly cross-linked human hemoglobin. Effects of cross-links between different subunits.
Human deoxyhemoglobin cross-linked with trimesyl tris(3,5-dibromosalicylate) produces the previously reported cross-linked hemoglobin in which the epsilon amino groups of the two beta chain 82 lysyl residues are joined by a trimesyl bridge. Further specific modification of this protein directed to the alpha subunits with bis(3,5-dibromosalicyl)fumarate gives a doubly cross-linked material in which the epsilon-amino groups of the two alpha chain 99 lysyl residues are now joined by a fumaryl bridge. The singly cross-linked beta chain species binds oxygen cooperatively with a high oxygen affinity (P50 = 4.8 torr at pH 7.4). The addition of the second cross-linking reduces the oxygen affinity to 15.9 torr, which compares with 13.0 torr for the singly cross-linked alpha chain species. The doubly cross-linked hemoglobin retains significant cooperativity with a Hill coefficient of 2.3 compared with 3.0 for unmodified hemoglobin. Because some of the groups responsible for the Bohr effect are acylated, this doubly cross-linked hemoglobin exhibits 25% of the normal Bohr effect and less than 20% of the normal chloride effect. The use of two distinct cross-links within the same tetramer provides a material for physical and structural analysis as well as for further modifications for specific applications. The results indicate that the cross-link introducing the lowest oxygen affinity in the two singly cross-linked species appears to control the overall affinity in this doubly cross-linked species.
Hemoglobins↗