Tolerance to cooked egg in an egg allergic population.
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Child↗
Biomedical subjects
M Nguyen
Publications and source records attributed to M Nguyen.
[Acute colitis in Wegener's disease: a case report].
We report the case of a 52 year old man who was hospitalized within a context of a persistent deterioration of his general condition. He was suspected of having a chronic inflammatory colitis. A pulmonary radiography revealed the presence of voluminous bilateral excavated masses with hydro-aerical levels. After having refuted among others a suspicion of tuberculosis, the results of a thoracic percutaneous transpleural lung aspiration by needle under tomodensitometric control steered our diagnosis towards a vascularitis of the Wegener disease type. A treatment with corticotherapy in large doses completed with cyclophosphamid allowed for clinical, biological and radiological improvement. Wegener's granulomatosis usually starts in an insidious manner with febrile episodes and an impairment of the general condition associated with inflammatory biological signs, as observed in our patient. After these warning symptoms, come ORL and/or pulmonary and/or renal impairment, which represent the classical triad of diffused GW. However a certain number of particularities unusual for that diagnosis characterized our patient and prompted the discussion of this case.
Acute Disease↗
Molecular markers of cartilage breakdown and synovitis at baseline as predictors of structural progression of hip osteoarthritis. The ECHODIAH Cohort.
OBJECTIVE: To determine whether systemic markers of bone, cartilage, and synovium can predict structural progression of osteoarthritis (OA). METHODS: Patients with painful hip OA were treated with diacerein or placebo in a multicentre, prospective, double blind, 3 year follow up trial. The following information was collected at entry: demographics, characteristics of hip OA, and 10 markers: N-propeptides of collagen types I and III, cartilage oligomeric matrix protein, YKL-40, hyaluronan (sHA), matrix metalloproteinases-1 and -3, C reactive protein, C-terminal crosslinking telopeptides of collagen types I and II (uCTX-II). Radiographs were obtained at entry and every year. Structural progression was defined as a joint space decrease > or =0.5 mm or requirement for total hip replacement. Grouped survival analysis was performed with time to structural progression as dependent variable, and clinical data, radiographic findings, treatment groups (diacerein versus placebo), and markers as explanatory measures. RESULTS: In the 333 patients in whom all markers were measured, high functional impairment, a joint space width <2 mm, and lateral migration of the femoral head at baseline increased the risk of progression, but diacerein had a protective effect (relative risk = 0.75; 95% confidence interval (CI) 0.54 to 0.96). In addition, patients in whom uCTX-II and sHA were in the upper tertile had a relative risk of progression of 3.73 (95% CI 2.48 to 5.61) compared with patients with markers in the two lower tertiles. CONCLUSION: In this large cohort, combined measurements of uCTX-II and sHA were a new predictor of the structural progression of hip OA.
Aged↗
Predictive value of anti-cell and anti-human immunodeficiency virus (HIV) humoral responses in HIV-1-exposed seronegative cohorts of European and Asian origin.
Unconventional immune responses have been demonstrated in individuals who, despite repeated exposure to human immunodeficiency virus (HIV) infection, remain seronegative. As environmental exposure to pathogens and genetic background may modulate immune responses differentially, one Italian and two Asian populations of HIV-1-exposed seronegative individuals were studied. In serum samples from each group, IgG to CCR5, IgG to CD4 and IgA to gp41 were measured, which were previously described as markers of unconventional immunity in HIV-exposed seronegative Caucasians. Given the importance of conformational epitopes in virus-cell interactions, IgG to CD4-gp120 complex was also measured. It was found that markers of HIV exposure were present in all populations studied. HIV-specific humoral responses (IgA to gp41 and IgG to CD4-gp120 complex) were extremely significant predictors of HIV exposure (P<0.0001 in both cases), whereas the predictive values of anti-cell antibodies (anti-CCR5 and anti-CD4) varied between populations. Evidence is provided for the correlation of these differences with route of exposure to HIV and level of natural antibodies to cross-reactive microbial antigens. In conclusion, exposed seronegative individuals of ethnically different origins display similar signs of HIV-dependent unconventional immunity. A specific relevance must be attributed to different innate and acquired factors.
Adolescent↗
QuantiFERON-TB predicts tuberculin skin test boosting in U.S. foreign-born.
SETTING: Santa Clara County, Northern California. OBJECTIVE: To characterize agreement of tuberculin skin test (TST) and QuantiFERON-TB (QFT) with repeated testing. DESIGN: Fifty-two subjects participating in an ongoing prospective study of infectious disease transmission were tested by TST and QFT at two home visits 3 months apart. Boosting was defined as reclassification of TST from negative to positive. Agreement and reproducibility of TST and QFT were assessed using kappa and McNemar statistics. RESULTS: Of 48 individuals completing all tests, 75% were foreign-born (92% Latin America) and 58% were BCG-vaccinated. Initial TST and QFT were positive in 13 (27%) and 21 (44%), respectively, with an overall agreement of 67% (K = 0.29). Ten (29%) of 35 initial TST-negative reactions boosted, nine of whom were BCG-vaccinated subjects. Boosting occurred in eight (67%) of 12 subjects who were initially QFT-positive/TST-negative. Compared to the second TST, initial QFT had a relative post-test probability of 76% (95% CI 0.58-0.95); boosting accounted for 8/16 (50%) of initial testing discordances. CONCLUSION: Positive QFT in the setting of negative TST frequently anticipates a TST boost. This finding helps explain discordance between the two tests and may provide an alternative to serial TST testing.
Adolescent↗
[Intrapulmonary lung sequestration: a case report].
Through the presentation of a classical case of intrapulmonary pulmonary sequestration, the nosology of congenital lung malformations is reviewed. The histology, imaging, and surgical treatment of this congenital anomaly are briefly discussed.
Adult↗
The DNA sequence and comparative analysis of human chromosome 10.
The finished sequence of human chromosome 10 comprises a total of 131,666,441 base pairs. It represents 99.4% of the euchromatic DNA and includes one megabase of heterochromatic sequence within the pericentromeric region of the short and long arm of the chromosome. Sequence annotation revealed 1,357 genes, of which 816 are protein coding, and 430 are pseudogenes. We observed widespread occurrence of overlapping coding genes (either strand) and identified 67 antisense transcripts. Our analysis suggests that both inter- and intrachromosomal segmental duplications have impacted on the gene count on chromosome 10. Multispecies comparative analysis indicated that we can readily annotate the protein-coding genes with current resources. We estimate that over 95% of all coding exons were identified in this study. Assessment of single base changes between the human chromosome 10 and chimpanzee sequence revealed nonsense mutations in only 21 coding genes with respect to the human sequence.
Animals↗
Critical period for a teratogenic VLA-4 antagonist: Developmental effects and comparison of embryo drug concentrations of teratogenic and non-teratogenic VLA-4 antagonists.
BACKGROUND: Integrins such as VLA-4 (Very late antigen 4, integrin alpha4beta1) play key roles in cell-cell interactions that are critical for development. Homozygous null knockouts of the VLA-4 alpha4-subunit or VCAM-1 (VLA-4 cell surface ligand) in mice result in failure of the allantois and chorion to fuse leading to interrupted placentation and cardiac development and embryo lethality. Embryo-fetal studies of three VLA-4 antagonists, IVL745, IVL984, and HMR1031 [Crofts et al., Birth Defects Res B 71:55-68 (this issue), 2004] with exposure on gestation days (GD) 6-17 (rat), 6-18 (rabbit) or 6-15 (mouse) showed that only IVL984 treatment resulted in embryo lethality and cardiac defects. Objectives of the current study were to determine the critical period for inducing IVL984-related embryo-fetal effects, and to test the hypothesis that these effects were due to higher embryo drug concentrations. METHODS: IVL984 was administered at 40 mg/kg/day to pregnant rats on GD 4 and 5, GD 6 and 7, GD 8 and 9, GD 10 and 11, or GD 12 and 13. Animals were euthanized on GD 21 and uteri and fetuses were examined. A treatment period of GD 10-12 was selected for subsequent toxicokinetic (TK) studies in which IVL984, HMR1031, or IVL745 was administered to pregnant rats and rabbits. On GD 12, maternal plasma, extra-embryonic tissue (placenta and amniotic fluid), and embryonic tissue were collected and analyzed for drug concentrations. RESULTS: In the IVL984 critical period study in pregnant rats, treatment on GD 10 and 11 resulted in increased post-implantation loss, skeletal variations, and spiral septal defects similar to those observed in standard embryo-fetal development studies with treatment throughout organogenesis. There were no embryo-fetal effects after treatment on GD 4 and 5, GD 6 and 7, or GD 8 and 9. There was a single aorta malformation after treatment on GD 12 and 13. In the TK studies, IVL745, HMR1031, and IVL984 were all detectable in embryonic tissue and there was no evidence for accumulation. Rat and rabbit embryo exposures (AUC or dose-adjusted AUC) on GD 12 could not explain the observed teratology (IVL984<HMR1031<IVL745). Further analyses incorporating pharmacological activity, clearance, and protein binding data provided a positive correlation between embryonic exposure and teratogenic potency. CONCLUSIONS: The critical period for IVL984 in the rat, GD 10 to 11, corresponds to the expression of alpha-4 integrin on the chorion and VCAM-1 on the allantois and myocardium as well as chorioallantoic fusion and formation of the spiral septum. Embryo drug levels adjusted for pharmacological activity, clearance, and protein binding provide a possible explanation for the differing teratogenic potency of IVL984, HMR1031, and IVL745.
Abnormalities, Drug-Induced↗
1,25-Dihydroxyvitamin D3 and fetal lung maturation: immunogold detection of VDR expression in pneumocytes type II cells and effect on fructose 1,6 bisphosphatase.
Lung maturation before birth includes type II pneumocyte differentiation with progressive disappearance of glycogen content and onset of surfactant synthesis. We have shown previously that 1,25-(OH)2D3 increases surfactant synthesis and secretion by type II cells and decreases their glycogen content in fetal rat lung explants. Recently, the gene coding fructose 1,6 bisphosphatase (F1,6BP), a regulatory enzyme of gluconeogenesis, has been identified in type II cells and its promoter bears a Vitamin D response element. Present results show:The coexistence of type II cells at different stages of maturation. in rat fetal lung on day 21 of gestation (electron microscopy), and the association between maturation of type II cells and disappearance of their glycogen content. The immunogold labeling of all type II cells when using the 9A7g VDR-antibody, with significantly more abundant gold particles in cells exhibiting an intermediate glycogen content. The expression of F1,6BP mRNA in a human type II cell line (NCI-H441) and the increase of this expression after 18h incubation with 1,25-(OH)2D3 (10(-8)M). These results bring further evidence for a physiological role of 1,25-(OH)2D3 during type II pneumocyte maturation. Activation of F1,6BP may participate to the 1,25-(OH)2D3 action on surfactant synthesis via the gluconeogenesis pathway.
Animals↗
Impact of low frequency transcutaneous electrical nerve stimulation on symptomatic diabetic neuropathy using the new Salutaris device.
In a double blind, randomised study, 19 patients suffering from mild-to-moderate symptomatic diabetic neuropathy (Total Symptom Score, NTSS 4-16) received either treatment with the new transcutaneous electrical nerve stimulation (TENS) device "Salutaris" (verum group) or a placebo treatment with an identical but electrically inactive device (placebo group). Stimulation pads were placed at the anatomical localisation of the peroneal nerve and stimulation was performed using a low frequency mode. At baseline (V1), after 6 (V2), and 12 (V3) wk of treatment, the patients' symptoms were registered using the new total symptom score (NTSS-6) and a visual analogue scale (VAS). In addition, sensory nerve thresholds (temperature, vibration, pain) and microvascular function were measured at the lower limb at baseline and after 12 wk of treatment. Active TENS-treatment resulted in a significant improvement in NTSS-6 score after 6 wk (-42%) and after 12 wk (-32%) of treatment (baseline: 10.0+/-3.3, 6 wk: 5.8+/-5.0, p<0.05; 12 wk: 6.8+/-3.9, p=0.05; placebo group: baseline: 7.6+/-3.1; 6 wk: 8.1+/-5.1, n.s.; 12 wk: 6.5+/-6.1, n.s.). Subanalysis of the different qualities of the NTSS-score revealed an improvement in numbness (2.2+/-1.0 to 1.6+/-1.3; p<0.03); lancinating pain (1.6+/-1.1 to 0.6+/-0.9; p<0.02) and allodynia (1.4+/-1.6 to 0.5+/-1.0; p<0.05). Also, a significant improvement in the VAS rating was found after 6 wk of TENS therapy (19.8+/-5.0 to 14.4+/-9.6; p<0.05), while no change was observed in the placebo arm. In conclusion, our study indicates that the new TENS device "Salutaris" is a convenient, non-pharmacological option for primary or adjuvant treatment of painful diabetic neuropathy.
Aged↗
Update-surveillance of health care workers exposed to blood, body fluids and bloodborne pathogens in Canadian hospital settings: 1 April, 2000, to 31 March, 2002.
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Blood-Borne Pathogens↗
Sex differences in hip osteoarthritis: results of a longitudinal study in 508 patients.
OBJECTIVE: To evaluate sex differences in the clinical and structural presentation, and natural history of hip OA. METHODS: A multicentre, prospective, longitudinal, five year follow up study of 508 patients (302 women, 206 men, mean age 63 (7) years) with painful hip OA. Data collected were baseline demographics, symptomatic, therapeutic, and structural variables; symptomatic variables and changes in joint space width (JSW) during the first year's follow up; requirement for total hip arthroplasty (THA) between the end of the first and fifth years. STATISTICAL ANALYSIS: evaluation of sex differences (a) at baseline, in the main characteristics of hip OA using multivariate logistic regression; (b) during the first year of follow up, in the radiological progression of the disease; (c) during the five years of follow up, in the requirement for THA using Kaplan-Meier curves and the log rank test, and of the parameters related to THA, using a multivariate Cox analysis. RESULTS: At entry, women presented more frequently than men with polyarticular OA (mean (SD) articular score 306 (162) v 235 (127)), and superomedial migration of the femoral head (40% v 19%), and had more severe symptomatic disease (patient's overall assessment 46 (23) v 40 (26)). The change in JSW did not differ between women and men after one year, but a greater proportion of women had rapid structural progression (OR=2.34, 95% CI 1.1 to 5.2). THA was performed more often in women. Multivariate analysis suggested that the decision to perform surgery was related more closely to the symptomatic and structural severity of the disease than to the sex of the patient. CONCLUSION: Hip OA in women is more frequently part of a polyarticular OA, and displays greater symptomatic and structural severity.
Aged↗
Relevant change in radiological progression in patients with hip osteoarthritis. I. Determination using predictive validity for total hip arthroplasty.
OBJECTIVE: To determine a cut-off point above which a change in joint space width (JSW) could be considered as relevant in patients with hip osteoarthritis (OA) on the basis of predicted need for subsequent total hip arthroplasty (THA). METHODS: A multicentre, prospective, longitudinal, 5-yr follow-up study was performed. A pelvic radiograph was obtained at entry and after 1 and 2 yr. For each film, the narrowest JSW was measured using a 0.1 mm graduated magnifying glass. The absolute and relative differences between baseline and 1 and 2 yr of follow-up were calculated. We determined the cut-off points above which an absolute or relative decrease in JSW between baseline and 1 and 2 yr of follow-up could be considered relevant on the basis of the predicted need for THA during the remaining years of the study. The need for THA was categorized as 'yes' or 'no'. Thereafter, for each observed change in JSW (0.1 per 0.1 mm or 1% per 1%), the sensitivity and specificity for subsequent THA were calculated. The choice of cut-off was based on maximal sensitivity and specificity, using the graphic representation of correct classification probabilities. In this way it was possible to obtain the best measured JSW threshold with maximal true positive and minimal false positive results. RESULTS: A total of 423 and 385 patients met the criteria for analysis using the decrease in JSW between baseline and 1 and 2 yr respectively. The best cut-off points were absolute decreases in JSW of 0.2 and 0.4 mm and relative decreases in JSW of 15 and 20% after 1 and 2 yr respectively, with corresponding ranges of sensitivity and specificity of 68-75 and 67-78%. CONCLUSION: This work determined the cut-off above which a change in JSW could be considered clinically relevant in patients with hip OA, on the basis of predicted subsequent need for THA. For validation, similar studies should be conducted in other countries with different health-care systems.
Aged↗
Relevant change in radiological progression in patients with hip osteoarthritis. II. Determination using an expert opinion approach.
AIM: To determine the minimum clinically important difference (MCID) in joint space width (JSW) progression in patients with hip osteoarthritis (OA), based upon evaluation by a panel of clinical experts as a gold standard. METHODS: A sample of 298 patients with hip OA was selected from a multicentre, prospective, longitudinal, 3-yr follow-up study. A pelvic radiograph was obtained at entry and after 3 yr. For each film, the narrowest JSW was measured using a 0.1-mm graduated magnifying glass. The difference between baseline and 3-yr follow-up JSW was calculated. Two senior rheumatologists, who were experts in osteoarthritis, evaluated each pair of films and noted whether a clinically relevant deterioration in osteoarthritis stage occurred at 3 yr compared with baseline. Interobserver reliabilities were evaluated using the kappa coefficient and proportions of agreements. Then, for each measured difference in JSW (0.1 mm per 0.1 mm), the sensitivity and specificity for MCID, defined as the assessment of expert 1, expert 2 or a combination of both, were calculated. This allowed us to obtain, from graphic representations of the correct classification probabilities, the best measured JSW threshold, with the maximal true positive and the minimal false positive results. RESULTS: The mean measured change in JSW was -0.63 +/- 0.74 mm. Experts 1 and 2 considered the decrease in JSW to be clinically relevant in 122 (40.9%) and 100 pairs (33.6%) respectively. The proportion of agreements between the experts was 79.9%, with a kappa coefficient of 0.572. The best measured JSW threshold was -0.4 mm for expert 1, expert 2 and the combination of both; sensitivity and specificity were 0.75 and 0.8, 0.71 and 0.72, and 0.75 and 0.7 respectively. CONCLUSION: This study suggests that a change of at least 0.4 mm in the radiological JSW could be considered clinically relevant. Other studies using other sets of patients and other methods are needed for validation.
Aged↗
[Image of the month. "The jewels of the crown"].
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Aged↗
Update. Surveillance of healthcare workers exposed to blood/body fluids and bloodborne pathogens: 1 April, 2000 to 31 March, 2001.
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Blood-Borne Pathogens↗
Double-blind, randomized trial of an anti-CD18 antibody in conjunction with recombinant tissue plasminogen activator for acute myocardial infarction: limitation of myocardial infarction following thrombolysis in acute myocardial infarction (LIMIT AMI) study.
BACKGROUND: Inhibition of leukocyte adhesion can reduce myocardial infarct size in animals. This study was designed to define the safety and efficacy of a recombinant, humanized, monoclonal antibody to the CD18 subunit of the beta2 integrin adhesion receptors (rhuMAb CD18), in reducing infarct size in patients treated with a thrombolytic agent. METHODS AND RESULTS: The Limitation of Myocardial Infarction following Thrombolysis in Acute Myocardial Infarction Study (LIMIT AMI) was a randomized, double-blind, placebo-controlled, multicenter study conducted in 60 centers in the United States and Canada. A total of 394 subjects who presented within 12 hours of symptom onset with ECG findings (ST-segment elevation) consistent with AMI were treated with recombinant tissue plasminogen activator and were also given an intravenous bolus of 0.5 or 2.0 mg/kg rhuMAb CD18 or placebo. Coronary angiography was performed at 90 minutes, 12-lead ECGs were obtained at baseline, 90, and 180 minutes, and resting sestamibi scans were performed at >/=120 hours. Adjunctive angioplasty and use of glycoprotein IIb/IIIa antiplatelet agents at the time of angiography were discretionary. There were no treatment effects on coronary blood flow, infarct size, or the rate of ECG ST-segment elevation resolution, despite the expected induction of peripheral leukocytosis. A slight trend toward an increase in bacterial infections was observed with rhuMAb CD18 (P=0.33). CONCLUSIONS: RhuMAb CD18 was well tolerated but not effective in modifying cardiac end points.
Antibodies, Monoclonal↗
A fast and efficient metal-mediated oxidation of isoniazid and identification of isoniazid-NAD(H) adducts.
It is currently believed that isoniazid (INH) is oxidised inside Mycobacterium tuberculosis to generate, by covalent attachment to the nicotinamide ring of NAD(H) (beta-nicotinamide adenine dinucleotide), a strong inhibitor of InhA, an enzyme essential for mycolic acid biosynthesis. This work was carried out to characterise the InhA inhibitors (named INH-NAD(H) adducts) which are generated, in the presence of the nicotinamide coenzyme NAD+, by oxidation of INH with manganese(III) pyrophosphate, a nonenzymatic and efficient oxidant used to mimic INH activation by the catalase-peroxidase KatG inside M. tuberculosis. The oxidation process is almost complete in less than 15 minutes (in comparison to the slow activation obtained in the KatG-dependent process (2.5 hours) or in the nonenzymatic O2/Mn(II)-dependent activation (5 hours)). The alkylation of NAD+ by the postulated isonicotinoyl radical generates, in solution, a family of INH-NAD(H) adducts. Analyses with liquid chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS) and experiments performed with 18O- and 2H-labelled substrates allowed us to propose two open and four hemiamidal cyclised dihydropyridine structures as the main forms present in solution; these result from the combination of the isonicotinoyl radical and the nicotinamide part of NAD+. A small amount of a secondary oxidation product was also detected. Structural data on the forms present in solution should help in the design of inhibitors of enzymes involved in the biosynthesis of mycolic acids to act as potential antituberculosis drugs.
Antitubercular Agents↗