Intermittent treatment with inhaled steroids for deterioration of asthma due to upper respiratory tract infections

Upper respiratory tract infection (URTI) is a common cause of deterioration of asthma in children. We investigated if inhaled steroids (budesonide), started early after URTI, could reduce asthma. Thirty-one children, 3-10 years of age, with deterioration during URTI participated. The study design was double-blind, crossover and placebo-controlled. Peak-expiratory flow (PEF) and symptom scores were recorded. Four treatment periods of 9 days, two with budesonide and two with placebo, were planned. Treatment was started at the first sign of URTI. Budesonide/placebo was given by Turbuhaler at 0.2 mg qid for 3 days, tid for 3 and bid for the last 3 days. Twenty-two children completed 67 periods. Eleven visited the emergency room, only three during budesonide therapy. Five received oral steroids and two where admitted to hospital, all receiving placebo. Symptom scores were not significantly lower during budesonide treatment. PEF, both morning and evening, was significantly higher during budesonide than placebo (p = 0.015 and p = 0.022). Inhaled budesonide can attenuate exacerbation of URTI-induced asthma. Asthma, budesonide, infection, inhaled steroids, intermittent, prophylactic
J Svedmyr, Department of Paediatrics, Falu Hospital, S-791 82 Falun, Sweden     

Magnetic resonance angiography findings in the early post-carotid endarterectomy period

This preliminary study was designed to investigate the ability of multiple axial volume three-dimensional fourier transform (3DFT) time-of-flight (TOF) magnetic resonance angiography (MRA) to depict the carotid bifurcation in the early post-carotid endarterectomy period. Five patients underwent intra-operative digital subtraction angiography (DSA) and carotid MRA within 5 days of carotid endarterectomy. An axial volume fast imaging in steady-state precession (FISP) gradient-echo 3DFT TOF carotid MRA technique in this limited series appeared to display accurately the surgically significant abnormalities at the carotid bifurcation after endarterectomy. However, in normal or near-normal intra-operative DSA studies, overestimation of internal carotid artery stenoses was encountered. Postoperative MRA demonstrates potential as a useful non-invasive investigation after carotid endarterectomy but should be interpreted with caution until larger studies become available.     

Vinyl sulfide cyclized analogues of angiotensin II with high affinity and full agonist activity at the AT(1) receptor

Vinyl sulfide cyclized analogues of the octapeptide angiotensin II that are structurally related to the cyclic disulfide agonist c[Hcy(3,5)]Ang II have been prepared. The synthesis relies on the reaction of the mercapto group of a cysteine residue in position 3 with the formyl group of allysine incorporated in position 5 of angiotensin II. A mixture of the cis and the trans isomers was formed, and these were separated and isolated by RP-HPLC. Thus, the three-atom CH(2)[bond]S[bond]S element of the AT(1) receptor agonist c[Hcy(3,5)]Ang II has been displaced by a bioisosteric three-atom S[bond]CH[double bond]CH element. A comparative conformational analysis of the 13-membered ring systems of c[Hcy(3,5)]Ang II and the 13-membered cyclic vinyl sulfides with cis and trans configuration, respectively, suggested that all three systems adopted very similar low-energy conformations. This similarity was also reflected in the bioactivity. Both of the compounds that contained the ring systems encompassing the cis or trans vinyl sulfide elements between positions 3 and 5 exhibited K(i) values less than 2 nM and exerted full agonism at the AT(1) receptor. In contrast, vinyl sulfide cyclization involving the amino acid residues 5 and 7 rendered inactive compounds. The cyclic vinyl sulfides that have agonist activity were both shown to possess low-energy conformers compatible with the previously proposed 3D model for the bioactive conformation of Ang II.     

Prospective,randomized evaluation of a cuffed expanded polytetrafluoroethylene graft for hemodialysis vascular access

BACKGROUND: A cuffed expanded polytetrafluoroethylene (ePTFE) hemodialysis graft was developed to address the problem of recurrent stenosis at the graft-vein anastomosis. The purpose of this study was to compare graft patency and blood flow rates of cuffed and noncuffed (standard) ePTFE grafts placed for hemodialysis access. METHODS: Forty-eight patients were prospectively randomized and followed for up to 24 months after placement of a cuffed or standard ePTFE graft for hemodialysis access. Study end points included time to graft failure and blood flow rates on hemodialysis. RESULTS: Risk factors for graft failure were similar in both groups. However, the overall incidence of graft failure was significantly lower in the cuffed ePTFE graft group (P =.039). Graft patency rates in the cuffed versus standard groups were 64% versus 32% at 12 months (P =.037) and 58% versus 21% at 24 months (P =.0213). No cuffed ePTFE graft failed as a result of venous outflow stenosis. Average graft flow rates were similar when first measured 3 months postoperatively (845 mL/min, cuffed vs 715 mL/min, standard; P =.51) but declined more rapidly in the standard group (12 months, 623 vs 253 mL/min [P =.037]; 24 months, 531 vs 121 mL/min [P =.012]). CONCLUSIONS: The cuffed ePTFE graft was associated with increased blood flow rates during hemodialysis and improved graft patency compared with a standard ePTFE graft. Our results suggest a beneficial effect of the cuffed venous geometry for hemodialysis vascular access.     

Subclinical rejection in tacrolimus-treated renal transplant recipients

BACKGROUND: Subclinical rejection, defined as histologic acute rejection in the absence of graft dysfunction, has been suggested as a cause of chronic allograft rejection. In cyclosporine-treated patients, the incidence of subclinical rejection 3 months after transplant is reported to be approximately 30%. The intent of our study was to determine the incidence of subclinical rejection in tacrolimus-treated renal allograft recipients. METHODS: We prospectively studied the incidence of subclinical rejection on surveillance biopsies performed 3 months after transplantation in 114 patients transplanted between September 1, 1998 and November 30, 2000. All patients received tacrolimus, mycophenolate mofetil, and prednisone, and 56% received antibody induction. RESULTS: Subclinical rejection was detected in 2.6% of patients (3/114, 95% confidence interval 0.5-7.5%). Borderline changes were detected in 11% (12/114). Subclinical rejections were treated with bolus methylprednisolone. CONCLUSIONS: The incidence of subclinical rejection early after kidney transplantation is extremely low in tacrolimus-treated patients in whom early rejections are aggressively treated, suggesting that surveillance biopsies may not be necessary with this regimen.     

Brain imaging of human memory systems: between-systems similarities and within-system differences

There is much evidence for the existence of multiple memory systems. However, it has been argued that tasks assumed to reflect different memory systems share basic processing components and are mediated by overlapping neural systems. Here we used multivariate analysis of PET-data to analyze similarities and differences in brain activity for multiple tests of working memory, semantic memory, and episodic memory. The results from two experiments revealed between-systems differences, but also between-systems similarities and within-system differences. Specifically, support was obtained for a task-general working-memory network that may underlie active maintenance. Premotor and parietal regions were salient components of this network. A common network was also identified for two episodic tasks, cued recall and recognition, but not for a test of autobiographical memory. This network involved regions in right inferior and polar frontal cortex, and lateral and medial parietal cortex. Several of these regions were also engaged during the working-memory tasks, indicating shared processing for episodic and working memory. Fact retrieval and synonym generation were associated with increased activity in left inferior frontal and middle temporal regions and right cerebellum. This network was also associated with the autobiographical task, but not with living/non-living classification, and may reflect elaborate retrieval of semantic information. Implications of the present results for the classification of memory tasks with respect to systems and/or processes are discussed.