Axial T1ρ MRI as a diagnostic imaging modality to quantify proteoglycan concentration in degenerative disc disease

European Spine Journal - The aim of the study was to investigate if axial T1ρ MR images had similar accuracy as established sagittal T1ρ MRI for the assessment of proteoglycan...     

Transitions in Latent Classes of Sexual Risk Behavior Among Young Injection Drug Users Following HIV Prevention Intervention

We analyzed data from a large randomized HIV/HCV prevention intervention trial with young injection drug users (IDUs). Using categorical latent variable analysis, we identified distinct classes of sexual behavior for men and women. We conducted a latent transition analysis to test the effect of the intervention on transitions from higher to lower risk classes. Men who were in a high-risk class at baseline who received the intervention were 86 % more likely to be in a low-risk class at follow-up compared to those in the control group (p = 0.025). High-risk intervention participants were significantly more likely to transition to the class characterized by unprotected sex with a main partner only, while low-risk intervention participants were significantly less likely to transition to that class. No intervention effect was detected on the sexual risk behavior of women, or of men who at baseline were having unprotected sex with a main partner only.     

The endothelial protein C receptor (PROCR) Ser219Gly variant and risk of common thrombotic disorders: a HuGE review and meta-analysis of evidence from observational studies

The endothelial protein C receptor (EPCR) limits thrombus formation by enhancing activation of the protein C anticoagulant pathway, and therefore may play a role in the etiology of thrombotic disorders. The rs867186 single-nucleotide polymorphism in the PROCR gene (g.6936A > G, c.4600A > G), resulting in a serine-to-glycine substitution at codon 219, has been associated with reduced activation of the protein C pathway, although its association with thrombosis risk remains unclear. The present study is a highly comprehensive systematic review and meta-analysis, including unpublished genome-wide association study results, conducted to evaluate the evidence for an association between rs867186 and 2 common thrombotic outcomes, venous thromboembolism (VTE) and myocardial infarction (MI), which are hypothesized to share some etiologic pathways. MEDLINE, EMBASE, and HuGE Navigator were searched through July 2011 to identify relevant epidemiologic studies, and data were summarized using random-effects meta-analysis. Twelve candidate genes and 13 genome-wide association studies were analyzed (11 VTE and 14 MI, including 37,415 cases and 84,406 noncases). Under the additive genetic model, the odds of VTE increased by a factor of 1.22 (95% confidence interval, 1.11-1.33, P < .001) for every additional copy of the G allele. No evidence for association with MI was observed.     

The Production of High Affinity Monoclonal Antibodies to Human Chorionic Gonadotropin and Their Application to Immunoradiometric Assay

Abstract

Production of monoclonal antibodies against hCG has been studied using hCG as the antigen. This study reports the successful isolation of hybrid clones secreting monoclonal antibodies specific for hCG with an affinity constant higher than 10¹⁰M^?l. Of 23 fusions, only 17 fusions have produced positive clones which secrete antibodies giving high levels of binding with ^l25I-labelled hCG in the supernatant. Finally, 6 different monoclonal antibodies have been isolated; 4 of them, specific for the β-subunit, with a Ka approximately 1.1–4.0 ± 10¹¹M^?1 and 2 others, specific for the α-subunit, presenting an affinity of 2.5 ± 10¹⁰M^?l. When the antibodies specific for the β-subunit are used, specific and highly sensitive radioim-munoassays are obtained after only 3 hrs of incubation. Using iodinated monoclonal antibodies specific for the α-subunit and tubes coated with antibodies against the β-subunit, we have developped sensitive immunoradiometric assays.     

Failure of temozolomide and conventional doses of pegvisomant to attain biochemical control in a severe case of acromegaly

It has been suggested that treatment with adequate dose titration of pegvisomant, a GH antagonist, up to a maximum of 40 mg daily, can achieve IGF-1 normalisation in virtually all patients with acromegaly. On the other hand, temozolomide (TMZ), an alkylating cytostatic agent, has been reported to reduce pituitary tumour size and hormone hypersecretion in a small number of aggressive pituitary macroadenomas. In this paper we report the case of a patient resistant to very high doses of pegvisomant used in combination with somatostatin analogs (SSA) and to TMZ therapy. The patient, initially a 22 year-old man with an invasive GH-secreting pituitary macroadenoma (IGF-1, 371% upper limit of normal), had active acromegaly despite a repeat transsphenoidal surgery followed by radiotherapy and SSA (octreotide 800 μg sc daily) (IGF-1, 262% ULN). In combination with SSA, pegvisomant was started at 20 mg daily and doses were titrated up to 60 mg daily. IGF-1 was moderately reduced and stabilized at 200% ULN after 1 year of treatment. Serum pegvisomant level was 30,500 ng/l, the denaturalized GHBP concentration 1,120 pM and the endogenous GH level was 220 μg/l. Pegvisomant was stopped and TMZ therapy was given for 5 cycles. However, the patient reported an increase of acromegaly symptoms and the serum IGF-1 was raised to the same level prior to pegvisomant therapy. Consequently, pegvisomant was tried again with doses up to 100 mg daily finally resulting in normalisation of serum IGF-1 level and improvement of acromegaly symptoms and patient well-being. We conclude that in some patients with severe acromegaly refractory to multimodal therapy, biochemical control may be difficult to attain with conventional doses of pegvisomant or TMZ therapy.