Synthesis and polymerization of fluorinated acrylic monomers substituted in α-position, 2. Synthesis and polymerization of 2-perfluorohexylethyl α-acetoxyacrylate

The synthesis of 2-perfluorohexylethyl α-acetoxyacrylate (^b) H₂C?C(OAc)CO₂C₂H₄C₆F₁₃ ( 1 ) was performed in two steps starting from pyruvic acid and 2-perfluorohexylethanol (3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluoro-1-octanol) with an overall yield of about 50%. Esterification of pyruvic acid with the adequate fluorinated alcohol was followed by enol acetylation to give monomer 1 . Homopolymerization and copolymerization of 1 are easily carried out. From the kinetic study of the homopolymerization and copolymerization of 1 with styrene, the numerical values of the ratio square of the rate constant of propagation over the rate constant of termination k/k_t and of the copolymerization reactivity ratios r₁ and r₂ of the two monomers were determined.     

Anatomical bases for the puncture and injection of the shoulder joint

Summary Basing our study on serial cuts and dissections, we have analysed the various techniques for puncture and injection in the region of the shoulder, the scapulohumeral and acromioclavicular joints, the subdeltoid bursa, the peri-articular muscles and tendons and the suprascapular nerve.

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Bases anatomiques des ponctions et injections de l'épaule

Résumé A partir de coupes sériées et de dissections les auteurs étudient les différentes techniques de ponctions et injections pratiquées au niveau de la région de l'épaule, articulations scapulo-humérale et acromio-claviculaire, bourse sous-deltoïdienne, tendons des muscles péri-articulaires et nerf sus-scapulaire.

     

Receptors for neurohypophyseal hormones along the rat nephron: 125I-labelled d(CH2)5[Tyr(Me)2, Thr4, Orn8, Tyr-NH 2 9 ] vasotocin binding in microdissected tubules

A microassay was developed to measure the binding of the labelled monoiodinated analogue [1-(mercapto-,-cyclopentamethylenepropionic acid), 2-O-mithyltyrosine, 4-threonine, 8-ornithine, 9-¹²⁵I-tyrosylamide]vasotocin ¹²⁵I-d(CH₂)₅[Tyr (Me)², Thr⁴, Tyr-NH ₂ ⁹ ]OVT to isolated nephron segments microdissected from collagenase-treated rat kidneys. When determined using 1.7 nM labelled ligand at 4° C, specific binding sites (expressed at 10^–18 mol ¹²⁵I-d(CH₂)₅[Tyr (Me)², Thr⁴, Tyr-NH ₂ ⁹ ]OVT bound/mm tubule length) were found in medullary thick ascending limbs (MTAL), 1.67±0.49; cortical thick ascending limbs, 2.20±0.80; cortical collecting ducts, 2.39±0.86; outer medullary collecting ducts (OMCD), 2.54±0.53 and inner medullary collecting ducts, 5.33±0.40, whereas no specific binding could be detected in glomeruli and proximal tubules. Specific ¹²⁵I-d(CH₂)₅[Tyr (Me)², Thr⁴, Tyr-NH ₂ ⁹ ]OVT binding to OMCD was saturable with incubation time and reversible after elimination of free labelled ligand (the association and dissociation rate constants at 4° C were 1.06×10⁷ M^–1 min^–1 and 1.95×10^–2 min^–1 respectively). The stereospecificity of MTAL and OMCD binding sites was assessed in competitive experiments revealing the following recognition pattern for a series of eight vasopressin analogues:ddAVP>AVP>d(CH₂)₅-[Tyr (Me)², Thr⁴, Tyr-NH ₂ ⁹ ]OVT=AVT=OT>d(CH₂)₅[Tyr(Me)²]AVP=[Thr⁴, Gly⁷]OT>[Phe², Orn⁸]VT, whereas pharmacological concentrations of insulin and glucagon did not impair radioligand binding. These results indicate that the detected labelled binding sites might correspond mainly to physiological V₂ vasopressin receptors.     

Influence of surgery on renal amyloidosis

It is well known that renal amyloidosis (RA) leads to ESRD in a few years. This evolution may be accelerated by several factors such as steroids, renal vein thrombosis, infections or surgery. We report 22 patients (14M,8F) mean age = 41.6 years (13-72) with RA in whom surgery revealed or aggravated renal disease. The group I includes 15 patients with no previous history of renal disease and who developed oedema few days after surgery with acute renal failure in 5 of them. Proteinuria was present in all the cases with a nephrotic syndrome in 10. Percutaneous kidney biopsy (KB) showed renal amyloidosis in all patients (AA+ = 8 cases, AA- = 3 cases). Only 9 patients were followed-up (mean period = 40 months): 2 patients are stationary; 1 is on complete remission 2 are on HD and 4 died. The group II includes 7 patients with a previous history of nephropathy (Histologically proven amyloidosis: 3 CRF = 1, Oedema: 3). All these patients developed oedema few days after surgery with acute RF in 4 patients. KB performed in all of them showed RA (AA+ = 33, AA- = 1). 6 patients were followed up for a mean period of 11 months: 5 died, 1 patient is on HD. The influence of surgery on renal amyloidosis is often unforeseeable. It may have no effect on renal disease, but very often it reveals RA and sometimes dramatically aggravates the course of the disease with occurrence of irreversible CRF. The pathogenic role of surgery on RA is discussed.     

Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial--INTACT 2.

PURPOSE: Preclinical studies indicate that gefitinib (Iressa, ZD1839; AstraZeneca, Wilmington, DE), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, may enhance antitumor efficacy of cytotoxics, and combination with paclitaxel and carboplatin had acceptable tolerability in a phase I trial. Gefitinib monotherapy demonstrated unparalleled antitumor activity for a biologic agent, with less toxicity than docetaxel, in phase II trials in refractory, advanced non-small-cell lung cancer (NSCLC). This phase III, randomized, placebo-controlled, double-blind trial evaluated gefitinib plus paclitaxel and carboplatin in chemotherapy-naive patients with advanced NSCLC. PATIENTS AND METHODS: Patients received paclitaxel 225 mg/m(2) and carboplatin area under concentration/time curve of 6 mg/min/mL (day 1 every 3 weeks) plus gefitinib 500 mg/d, gefitinib 250 mg/d, or placebo. After a maximum of six cycles, daily gefitinib or placebo continued until disease progression. End points included overall survival, time to progression (TTP), response rate (RR), and safety evaluation. Results A total of 1,037 patients were recruited. Baseline demographic characteristics were well balanced. There was no difference in overall survival (median, 8.7, 9.8, and 9.9 months for gefitinib 500 mg/d, 250 mg/d, and placebo, respectively; P =.64), TTP, or RR between arms. Expected dose-related diarrhea and skin toxicity were observed in gefitinib-treated patients, with no new significant/unexpected safety findings from combination with chemotherapy. Subset analysis of patients with adenocarcinoma who received > or = 90 days' chemotherapy demonstrated statistically significant prolonged survival, suggesting a gefitinib maintenance effect. CONCLUSION: Gefitinib showed no added benefit in survival, TTP, or RR compared with standard chemotherapy alone. This large, placebo-controlled trial confirmed the favorable gefitinib safety profile observed in phase I and II monotherapy trials.     

Lymphoproliferative disorders in kidney transplant recipients: incidence, clinical characteristics and outcome

PURPOSE: The aim of this study was to determine the epidemiological and the clinical characteristics of post-transplant lymphoproliferative disease (PTLD) and to evaluate its impact on patients' and grafts' survival. PATIENTS AND METHODS: Three hundred and sixteen adult kidney recipients, transplanted between June 1986 and May 2006, were included. The incidence rates were calculated by dividing the number of different events (PTLD, death and graft-loss) by the total duration of follow-up. The survival rates and the cumulated frequency of PTLD were calculated according to the actuarial method. RESULTS: Seven recipients developed PTLD during a cumulated follow-up of 2202 years. The annual incidence was of 0.32% (95% CI : 0.30-0.34). It was of 0.81% (0.70-0.92) in recipients of kidneys from deceased donors, and of 0.25% (0.23-0.27) in patients transplanted from living donors (NS). The delay after transplantation for the diagnosis of PTLD ranged from 7.4 months to 7.7 years. PTLD was a B cell lymphoma in six cases and affected extra nodal sites in most of the cases. The treatment, comprising the cessation of immunosuppressive therapy in all cases, resulted in complete remission in four patients. Three patients died, representing an annual death rate of 6.1%, versus 2.8% in patients without PTLD (NS). The annual incidence of graft loss was 6.1% versus 3.2% among patients without PTLD (NS). CONCLUSION: PTLD was observed in 2.2% of our patients, with an annual incidence of 0.32%. It resulted in a decrease of both patients' and grafts' survivals. Preventive measures, including the improvement of the monitoring of immunosuppressive drugs and the prevention of viral infections, should be considered to reduce the risk of PTLD.     

Expanding the clinical spectrum of STIP1 homology and U-box containing protein 1-associated ataxia

Journal of Neurology - STUB1 has been first associated with autosomal recessive (SCAR16, MIM# 615768) and later with dominant forms of ataxia (SCA48, MIM# 618093). Pathogenic variations in STUB1...     

Interferon α and Tat involvement in the immunosuppression of uninfected T cells and C-C chemokine decline in AIDS

HIV type 1 (HIV-1) not only directly kills infected CD4⁺ T cells but also induces immunosuppression of uninfected T cells. Two immunosuppressive proteins, interferon α (IFNα) and extracellular Tat, mediate this process because specific antibodies against these proteins prevent generation of suppressor cells in HIV-1-infected peripheral blood mononuclear cell cultures. Furthermore, the production of C-C chemokines in response to immune cell activation, initially enhanced by IFNα and Tat, ultimately is inhibited by these proteins in parallel with their induction of immunosuppression. The clinical corollary is the immunosuppression of uninfected T cells and the decline in C-C chemokine release found at advanced stages of HIV-1 infection paralleling rising levels of IFNα and extracellular Tat. We, therefore, suggest that IFNα and Tat may be critical targets for anti-AIDS strategies.