Mesenteritis precedes vasculitis in the rat mesentery after subacute administration of a phosphodiesterase type 4 inhibitor

Inhibitors of phosphodiesterase type 4 (PDE4) are currently exploited as potent drugs for pulmonary diseases. Some PDE4 inhibitors induce necrotizing panarteritis in the mesentery of rats, comparable to spontaneous polyarteritis nodosa in rats and vascular alterations that are induced by various vasoactive compounds, such as fenoldopam and inhibitors of PDE3. The mechanism of toxicity is unknown. In order to investigate the development of arteritis in the splanchnic vasculature of rats, a time-course study was performed with high doses of a compound (BYK169171), specifically inhibiting PDE4. Rats were treated orally for 1-28 days, and alterations in the mesentery were evaluated by histology, morphometry, and immunohistology. As early as 3 days after the onset of treatment, a mesenteritis was found, characterized by macrophage infiltration, fibroblast proliferation, neovascularization, and loss of adipocytes. Incidence and severity of the mesenteritis were low during the first 2 weeks of treatment, but increased with duration of treatment, finally affecting 2/3 of all animals. A segmental necrotizing panarteritis was detected in some rats treated for 21 or 28 days, but always followed a mesenteritis, whereas many animals with mesenteric inflammation did not have vascular lesions. We postulate that PDE4 inhibitors do not cause a primary vasculitis/arteritis in rats, but induce a non-purulent inflammation as the predominant initial toxic effect in the mesentery. This renders their toxic effect distinct from that of PDE3 inhibitors.     

COMPREHENSIVE ASSESSMENT AND MANAGEMENT OF ATHLETES WITH SPORT CONCUSSION

Currently, the popular approach to post-concussion management of the athlete relies upon the use of a multidisciplinary team of healthcare providers, all typically coordinated by a physician. That core team is often supplemented by nurses, psychotherapists, coaches, teachers, the athletic director, and, of course, family members. However, access to such a model is frequently limited by financial, geographical, and numerous other factors. In the absence of such resources, a thorough clinical evaluation and management by an available, ongoing healthcare provider, quite often the sports physical therapist, becomes necessary.The authors recommend that the professional who coordinates the athlete''s post-concussion healthcare should focus efforts upon a comprehensive assessment and tailored treatment plan specific to the athlete''s post-concussive symptoms. Assessment of both pre-morbid function and post-injury physical, cognitive, psychosocial, emotional, and behavioral issues, including the patient''s support system, can assist the clinician with identifying specific constraints to sport, academic, social, and vocational activity participation. Hence, the assessment provides structure to the athlete''s individualized treatment plan. Successful specialized interventions that address the multi-faceted impairments of sport related concussion frequently require knowledge of resources in a variety of other healthcare professions, in order to facilitate appropriate and necessary treatment referrals.Initial assessment should be followed by repeat monitoring throughout treatment, and spanning a variety of environments, in order to ensure the athlete''s full recovery prior to return, not only to sport participation, but also to involvement in social, academic, and/or employment related life activities.

Level of Evidence:

5     

New daily persistent headache in the paediatric population

We conducted a clinic-based study focusing on the clinical features of new-onset chronic daily headaches (CDH) in children and adolescents. The clinical records and headache diaries of 306 children and adolescents were reviewed, to identify 187 with CDH. Relevant information was transferred to a standardized form that included operational criteria for the diagnoses of the headaches. Since we were interested in describing the clinical features of these headaches, we followed the criteria A and B of the 2nd edn of the International Classification of Headache Disorders (ICHD-2) and refer to them as new daily persistent headaches (NDPH) regardless of the presence of migraine features (therefore, this is a modified version of the ICHD-2 criteria). From the 56 adolescents with NDPH, most (91.8%) did not overuse medications. Nearly half (48.1%) reported they could recall the month when their headaches started. NDPH was more common than chronic tension-type headache in both adolescents overusing and not overusing medication. Individuals with NDPH had headaches fulfilling criteria for migraine on an average of 18.5 days per month. On most days, they had migraine-associated symptoms (one of nausea, photophobia or phonophobia)). NDPH is common in children and adolescents with CDH. Most subjects do not overuse medication. Migraine features are common.     

Nosocomial respiratory syncytial virus infection in Canadian pediatric hospitals: a Pediatric Investigators Collaborative Network on Infections in Canada Study

OBJECTIVE: To determine nosocomial transmission of respiratory syncytial virus (RSV) in Canadian pediatric hospitals, outcomes associated with nosocomial disease, and infection control practices. DESIGN: A prospective cohort study in the 1992 to 1994 winter respiratory seasons. SETTING: Nine Canadian pediatric university-affiliated hospitals. PARTICIPANTS: Hospitalized children with symptoms of lower respiratory tract infection (at least one of cough, wheezing, dyspnea, tachypnea, and apnea) and RSV antigen identified in a nasopharyngeal aspirate. RESULTS: Of 1516 children, 91 (6%) had nosocomial RSV (NRSV), defined as symptoms of lower respiratory tract infection and RSV antigen beginning >72 hours after admission. The nosocomial ratio (NRSV/[com-munity-acquired RSV {CARSV})] + NRSV) varied by site from 2.8% to 13%. The median length of stay attributable to RSV for community-acquired illness was 5 days, but 10 days for nosocomial illness. Four children with NRSV (4. 4%) died within 2 weeks of infection, compared with 6 (0.42%) with CARSV (relative risk = 10.4, 95% confidence interval: 3.0, 36.4). All sites isolated RSV-positive patients in single rooms or cohorted them. In a multivariate model, no particular isolation policy was associated with decreased nosocomial ratio, but gowning to enter the room was associated with increased risk of RSV transmission (incidence rate ratio 2.81; confidence interval: 1.65, 4.77). CONCLUSIONS: RSV transmission risk in Canadian pediatric hospitals is generally low. Although use of barrier methods varies, all sites cohort or isolate RSV-positive patients in single rooms. Children with risk factors for severe disease who acquire infection nosocomially have prolonged stays and excess mortality.     

高效液相色谱法测定人血清盐酸劳卡尼浓度

介绍了一种测定人血清盐酸劳卡尼(lorcainide hydrochloride)浓度的高效液相色谱法(HPLC)。不锈钢分析柱(200mm×5mmID)固定相为YWG C₁₈H₃₇,5μm颗粒。流动相为甲醇-水-0.625mol·L^-1醋酸铵(86:13:1v/v),用浓氨水调至pH8.0。流速1ml·min^-1。取地尔硫(diltiazem)为内标物。紫外检测波长226nm。低、中、高3种浓度方法回收率分别为95.85%,100.63%,100.09%,由低至高四种浓度日内、日间RSD小于7%。血清最低检测浓度为5μg·L^-1。在20～800μg·L^-1浓度范围内线性良好,r=0.9996。     

MR imaging technology: maximizing the signal-to-noise ratio from a single tissue

The pulse-sequence equations for spin-echo magnetic resonance imaging were used to determine interpulse delay times that give the highest signal-to-noise ratio from a single tissue. This theoretical result was then verified experimentally using 1-, 2-, and 5-mM/l copper sulfate solutions imaged on a 0.15-T resistive system. Theoretical analysis determined the spin-echo interpulse delay times that maximize the signal-to-noise ratio from a single tissue as TEopt = TEmin, the minimum echo delay time permitted by the system, and, to a good approximation, TRopt = 1.27 T1 + 1.90 TEmin, with T1 the longitudinal magnetic relaxation time of the tissue. Phantom measurements of the signal-to-noise ratio in a typical imaging system confirmed the theoretically determined TRopt values to within 7%.