Detection of multiple allergen-specific IgEs on microarrays by immunoassay with rolling circle amplification.
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Biomedical subjects
Publications and source records attributed to J Lambert.
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BACKGROUND: In its 1993 report the Canadian Royal Commission on New Reproductive Technologies challenged the effectiveness of in vitro fertilization for severe male infertility. To address the Commission's concern, the authors compared the relative effectiveness of in vitro fertilization combined with intracytoplasmic sperm injection for severe male infertility and conventional in vitro fertilization for complete tubal occlusion in women. METHODS: This historical cohort study was done at the PROCREA Fertility Centre, a private tertiary human reproduction centre in Montreal. Three groups of infertile couples were compared: 122 couples with severe male infertility treated by in vitro fertilization with intracytoplasmic injection of fresh sperm from ejaculate (group 1); 27 couples with obstructive azoospermia treated by in vitro fertilization with intracytoplasmic injection of epididymal sperm (collected by microepididymal or percutaneous epididymal sperm aspiration) (group 2); and 98 couples with tubal factor infertility (bilateral tubal occlusion) treated with conventional in vitro fertilization (with sperm from ejaculate) (group 3). The main outcomes measured were rates of fertilization, pregnancy, clinical pregnancy and implantation. RESULTS: Pregnancy rates per started cycle were 35%, 40% and 34% for groups 1, 2 and 3 respectively. When prognostic factors were controlled for, none of the outcome measures differed significantly between the 3 groups. INTERPRETATION: In vitro fertilization with intracytoplasmic injection of sperm from the ejaculate or the epididymis is as effective for treating severe male infertility as conventional in vitro fertilization is for treating complete occlusion of the fallopian tubes in women.
The BL/VL(3) Kaplan radiation leukemia virus (RadLV-VL(3)) is a nondefective retrovirus that induces T cell lymphomas in several strains of mice. By using DNA probes derived from RadLV/VL(3) provirus-flanking sequences cloned from the BL/VL(3) cell line, we identified a DNA region rearranged in 5 of 19 tumors analysed (25%). All proviruses were integrated in the same 5'-to-3' orientation in a small DNA region called Kis1 (Kaplan integration site 1). This region was localized on distal mouse chromosome 2 in a region not previously identified as important to lymphomagenesis. The cells rearranged at the Kis1 locus represent a clonal subpopulation of the clonal tumor masses examined, indicating a probable role of Kis1 in tumor progression.
BACKGROUND: Granulomatous syndromes, such as Wegener's granulomatosis, are defined according to complex criteria, but the underlying cause is rarely identified. We present evidence for a new aetiology for chronic granulomatous lesions associated with a recessive genetic defect, which is linked to the human leucocyte antigen (HLA) locus. METHODS: Five adults with necrotising granulomatous lesions in the upper respiratory tract and skin, associated with recurrent bacterial respiratory infections and skin vasculitis, were identified. A diagnosis of Wegener's granulomatosis was considered in all of them, but abandoned because of an incompatible disease course and resistance to immunosuppressive treatments. Peripheral-blood samples were taken and analysed by immunohistochemistry and fluorescent-activated-cell-sorter analysis. Since all five patients were homozygous for the HLA locus, we looked for genetic defects located within the HLA-locus with PCR and restriction fragment length polymorphism. FINDINGS: A severe decrease in cell-surface expression of HLA class-I molecule was seen in all patients. Defective expression of the transporter associated with antigen presentation (TAP) genes was responsible for the HLA class-I down-regulation, and in two patients we identified a mutation in the TAP2 gene responsible for the defective expression of the TAP complex. We showed the presence of autoreactive natural killer (NK) cells and gammadelta T lymphocytes in the peripheral blood cells of two patients. Correction of the genetic defect in vitro restored normal expression of HLA class-I molecules and prevented self-reactivity in the patients' cells. Histology of granulomatous lesions showed the presence of a large proportion of activated NK cells. INTERPRETATION: Our findings define the cause and pathogenesis of a new syndrome that affects patients with a defective surface expression of HLA class-I molecules. The syndrome resembles Wegener's granulomatosis both clinically and histologically. Patients have chronic necrotising granulomatous lesions in the upper respiratory tract and skin, recurrent infections of the respiratory tract, and skin vasculitis. A predominant NK population within the granulomatous lesions suggests that the pathophysiology of the skin lesions may relate to the inability of HLA class-I molecules to turn off NK cell responses. Accurate genetic analysis of a defined syndrome can provide a better understanding of the cause and pathogenesis of a disease.
Statistical time series models are practical tools in public health surveillance. Their capacity to forecast future disease incidence values exemplifies their usefulness. Using these forecasts, one can develop strategies to trigger alerts to public health officials when irregular disease incidence values have occurred. Clearly, the better the forecasting performance of the model class used in the time series analysis, the more realistic are the alerts triggered. The time series analysis of disease incidence values has often entailed the Box and Jenkins model class. However, this class was designed to model real-valued variables whereas disease incidences are integer-valued variables. A new class of time series models, called integer-valued autoregressive models, has been developed and studied over the past decade. The objective of this paper is to introduce this new class of models to the application of time series analysis of infectious disease incidence, and to demonstrate its advantages over the class of real-valued Box and Jenkins models. The paper also presents a bootstrap method developed for the calculation of forecast interval limits.
Acute HIV-1 illness presents a wide range of clinical manifestations. We assessed a classification and data reduction of clinical features among 218 patients with acute HIV-1 infection enrolled in four prospective seroincidence studies. Factor analysis allows the definition of eight factors based on groups of symptoms and signs: gastrointestinal transit disturbances, weight loss/abdominal pain, lymphadenopathy, myalgia/arthralgia, neurologic features, constitutional and mucocutaneous features, oral candidiasis, and anorexia/pharyngitis. These groups reflected the main target systems involved at the time of acute HIV-1 disease. Grouping of symptoms and signs based on groups of patients is potentially more informative than observations made on individual patients. It might facilitate diagnosis, suggest pathogenic mechanisms and reduce the number of variables for characterizing acute HIV-1 illness.
Large artery stiffening could contribute to the development of cardiovascular disease. The aim of this study was to investigate associations between arterial stiffness and diameter with insulin sensitivity and body composition in healthy men and women. In healthy, young (< 41 years old), non-obese (BMI < 27 kg/m2) men (n = 17) and women (n = 17), we measured the arterial diameter, the distension, the distensibility coefficient and the compliance coefficient of the elastic common carotid and muscular femoral arteries with a non-invasive ultrasonographic method. We also assessed glucose uptake (by a euglycaemic hyperinsulinaemic clamp technique), total body fat and lean body mass (by bioelectrical impedance analysis) and abdominal subcutaneous and visceral fat area (by magnetic resonance imaging). In women, but not in men, the distension and distensibility and compliance coefficients of the femoral artery were negatively associated with insulin concentrations (beta = -0.62, p = 0.008; beta = -0.65, p = 0.005 and beta = -0.59, p = 0.01), and positively with glucose uptake (beta = 0.59, p = 0.02; beta = 0.68, p = 0.005 and beta = 0.54, p = 0.04). Associations with glucose uptake were independent of the mean arterial pressure and body composition. In men and women, arterial compliance was positively associated with fat mass variables, which were mediated by a strong association between the femoral artery diameter and lean body mass (beta = 0.80, p < 0.001) and between the common carotid artery diameter and visceral fat area (beta = 0.56, p = 0.001). We found an independent association between insulin resistance and arterial stiffness, which was more pronounced in women than in men.
OBJECTIVES: Mild hyperhomocysteinaemia, fasting as well as after a methionine load, occurs in families and is associated with premature atherosclerosis. We hypothesised that endothelial dysfunction plays a role in the relation between hyperhomocysteinaemia and clinical vascular disease. METHODS: In this study flow-mediated, endothelium-dependent vasodilatation of the brachial artery and, as a marker of biophysical changes of the vessel wall such as increased smooth muscle cell tone or collagen formation, arterial distensibility of the common carotid artery were investigated in 123 healthy first-degree relatives of patients with mild hyperhomocysteinaemia and coronary, cerebral or peripheral artery disease. RESULTS: In multiple linear regression analyses, the increase in the homocysteine concentration after a standard methionine load was a significant determinant of an impaired flow-mediated vasodilatation of the brachial artery (measured on a separate day). The only other predictors were the baseline vessel diameter and age. Fasting homocysteine level was not associated with flow-mediated vasodilatation in the brachial artery. There was no relationship between homocysteine levels and nitroglycerine-induced, endothelium-independent vasodilatation of the brachial artery. Arterial distensibility of the carotid artery was also not related to homocysteine levels. CONCLUSIONS: In healthy first-degree relatives of patients with mild hyperhomocysteinaemia, the increase in homocysteine level after a methionine load is an independent predictor of endothelial dysfunction. The results also suggest that fasting and post-methionine homocysteine levels may reflect distinct disturbances in methionine metabolism, which may be linked to vascular dysfunction through distinct mechanisms.
Two HIV infected patients with visceral leishmaniasis and unusual cutaneous lesions are described. The first patient developed linear brown macules containing Leishmania parasites on the fingers and palms of the hands. This patient never received highly active antiretroviral treatment and the visceral leishmaniasis could not be cured even with liposomal amphotericin. In the second patient, Leishmania parasites were present in a skin biopsy of a fibrous histiocytoma. After completing visceral leishmaniasis treatment, a discrete elevation of one of his tattoos was seen. A biopsy specimen of this tattoo revealed Leishmania amastigotes. In this patient the visceral leishmaniasis was finally cured with meglumine antimoniate, followed by pentacarinat isothianate as maintenance therapy in conjunction with highly active antiretroviral treatment.
An important aspect of malaria control strategies has been the use of prophylactic measures such as impregnated bednets; however, adoption of this strategy has been slow and uneven. This study considers the factors determining Permethrin Impregnated Bednets (PIB) use in the context of a PIB promotion project in a rural area of Benin undertaken between 1992 and 1995. Quantitative data, on socio-demographic characteristics, malaria knowledge, attitudes, and practices, were gathered from 191 households of PIB users and non-users for comparative purposes using a questionnaire format. Qualitative data were collected from 23 focus group discussion sessions and 16 semi structured interviews. Women's income, men's educational level, and women's participation in communal organizations were the principal variables distinguishing user households from non-user households. Recourse to non-western medicine and, in particular, to medicinal teas which are considered preventive or curative correlates negatively with PIB use. The qualitative data shows that informants consider exposure to the sun, especially while engaged in agriculture work, a principal cause of malaria, and that PIB adoption is not considered justified in a context where there is a quasi chronic shortage of financial resources and where confidence in the efficacy of non-western medicine prevails. Because they have primary responsibility for the health of their families and are more aware of children's vulnerability to malaria, women are more inclined than men to want to buy PIBs. However, because the household head, who is most often male, sets family consumption priorities using family income, women often have to resort to using their own income, which is often considerably lower than that of men, to buy PIBs. Support for community initiatives which are directed to women's work, linked with intensive effort to sensitize men to the mechanisms of malaria transmission and the principal groups at risk, is seen as a means to increase PIB acquisition and use.
In vivo bilateral microdialysis in the rat striatum was used to investigate hydroxyl radical formation under basal conditions and after intrastriatal administration of the neurotoxin, 1-methyl-4-phenylpyridinium (MPP+). After a short equilibration period, 4-hydroxybenzoate (4HBZ), which scavenges hydroxyl radicals to produce 3,4-dihydroxybenzoate (34DHB), was injected intraperitoneally 15 min before infusion of MPP+. To evaluate the enzymatic contribution to hydroxyl radical formation, two other series of microdialyses were performed following administration of monoamine oxidase B inhibitors, either 1-deprenyl (selegiline) or MDL 72,974A [(E)-2-(4-fluorophenethyl)-3-fluoroallylamine hydrochloride]. Microdialysate samples were analyzed by high-performance liquid chromatography for catecholamines, 3,4-dihydroxyphenylacetate (DOPAC), homovanillate (HVA), along with the hydroxyl radical adduct, 34DHB and its precursor, 4HBZ. MPP+ administration resulted in a massive release of dopamine along with a decrease in DOPAC and HVA in all three groups. A striking effect in all three groups was noted in which MPP+ resulted in a decrease in interstitial 4HBZ to < 50% of the non-MPP+ -treated side. In absolute terms, the amount of 34DHB produced was low but similar in all three groups, even after unilateral MPP+ infusion. When 34DHB was normalized to 4HBZ release to account for differences in precursor availability, there were no significant differences in the 34DHB/4HBZ ratios either with or without MAO inhibitor treatment or after local MPP+ infusion. Systemic 4HBZ administration appears to result predominantly in intra-cellular sampling of hydroxyl radicals which produces different results from local infusion of trapping agents such as salicylate.
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OBJECTIVE: To study the relative bioavailabilities of two generic rifampicin preparations with Rimactane. METHOD: Each of nineteen healthy volunteers received a single oral dose of 600 mg of rifampicin in an open cross-over randomised three-way single-dose design with a washout period of 7 days between each doses. Plasma concentrations of rifampicin were determined by HPLC. In vitro dissolution profiles of the same drugs were determined and compared with human bioavailability study results. RESULTS: No statistically significant difference was found in main bioavailability parameters between Rimactane and generic preparations studied. Both generic preparations also fulfilled the bioequivalence criteria based on the 90% confidence intervals. There was a good correlation between in vivo and in vitro results: faster dissolution time corresponded to the lower Tmax value; lower percentage of released compound to the lower AUC value. Significant intersubject variations were found in main bioavailability parameters; significant negative correlation was found between average AUC values and body weight of the volunteer. CONCLUSION: All three products were bioequivalent. Our results also suggest the suitability of one-compartmental model with lag time, first order input and first order output to describe the kinetics of rifampicin.
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The aim of this study was to investigate the early CD4+ T cell response among human immunodeficiency virus type 1 (HIV-1) seroconverters in relation to their year of seroconversion. Study participants were enrolled in the Swiss HIV Cohort Study between 1985 and 1995 and had not received antiretroviral treatment. The slope of the CD4+ T cell count within 2 years after seroconversion was significantly associated with the year of seroconversion, by sex and by use of injection drugs, when controlling for initial CD4+ cell count. These results show that the loss of CD4+ cells might be associated with the year of seroconversion, suggesting a change in the pathogenesis of HIV across the years. If these results are confirmed, they could have important implications for the pathogenesis of and therapeutic strategies for HIV-1 infection.
Cross-education enhances the performance of muscles not directly involved in the chronic conditioning of the muscles in a remote limb. Substantial cross-education occurs after training with eccentric contractions or with contractions evoked by electromyostimulation (EMS). Since during EMS and eccentric contractions, skin and muscle afferents are activated that have excitatory effects on contralateral homologous muscles, it was hypothesized that exercise training with stimulated vs. voluntary eccentric contractions would lead to greater cross-education. Thirty-two women were randomly assigned to a voluntary (Vol), an EMS, or remote EMS (rEMS) exercise group and performed 840 voluntary or stimulated eccentric contractions over 6 weeks. All subjects, including nonexercising controls (Con), were tested pre- and posttraining for maximal voluntary and stimulated isometric and eccentric quadriceps strength. Ipsilateral voluntary and stimulated forces increased in all groups. Changes in EMG activity paralleled those in voluntary force in each limb. No changes occurred in grip strength. The great contra- and ipsilateral strength gains after EMS training were most likely related to an additive effect of EMS and muscle lengthening.
This paper reflects the consensus reached among Belgian professors of dermatology on the place of cyclosporin (CsA) in the treatment of atopic dermatitis (AD). Existing therapeutic modalities and ways to evaluate efficacy of treatment are reviewed briefly. Based on data from the literature and personal experience, guidelines for the use of CsA in AD are proposed. CsA can be prescribed in recalcitrant cases of AD on a short-term basis, both in adults and children. Long-term treatment, up to 1 year, should be considered only in exceptional cases that cannot be controlled by short-time therapy. Contraindications, drug interactions and necessary controls during treatment are also discussed.