Evaluation of an open access echocardiography service in the Netherlands: a mixed methods study of indications,outcomes, patient management and trends

Background  

In our region (Eastern South Limburg, The Netherlands) an open access echocardiography service started in 2002. It was the first service of this kind in The Netherlands. Our study aims were: (1) to evaluate demand for the service, participation, indications, echocardiography outcomes, and management by the general practitioner (GP); (2) to analyse changes in indications and outcomes over the years.     

The negative inotropic action of canrenone is mediated by L-type calcium current blockade and reduced intracellular calcium transients

Background and purpose:

Adding spironolactone to standard therapy in heart failure reduces morbidity and mortality, but the underlying mechanisms are not fully understood. We analysed the effect of canrenone, the major active metabolite of spironolactone, on myocardial contractility and intracellular calcium homeostasis.

Experimental approach:

Left ventricular papillary muscles and cardiomyocytes were isolated from male Wistar rats. Contractility of papillary muscles was assessed with force transducers, Ca²⁺ transients by fluorescence and Ca²⁺ fluxes by electrophysiological techniques.

Key results:

Canrenone (300–600 µmol·L⁻¹) reduced developed tension, maximum rate of tension increase and maximum rate of tension decay of papillary muscles. In cardiomyocytes, canrenone (50 µmol·L⁻¹) reduced cell shortening and L-type Ca²⁺ channel current, whereas steady-state activation and inactivation, and reactivation curves were unchanged. Canrenone also decreased the Ca²⁺ content of the sarcoplasmic reticulum, intracellular Ca²⁺ transient amplitude and intracellular diastolic Ca²⁺ concentration. However, the time course of [Ca²⁺]_i decline during transients evoked by caffeine was not affected by canrenone.

Conclusion and implications:

Canrenone reduced L-type Ca²⁺ channel current, amplitude of intracellular Ca²⁺ transients and Ca²⁺ content of sarcoplasmic reticulum in cardiomyocytes. These changes are likely to underlie the negative inotropic effect of canrenone.     

A 3-year longitudinal analysis of changes in fitness, physical activity, fatness and screen time

Aim:  To analyse whether changes in physical activity index (PAI), screen time (ST: television, computer) and body mass index (BMI) made a contribution to longitudinal changes in fitness of children and adolescents. Additionally, we analysed the interaction between baseline fitness level and changes in fitness.
Methods:  This is a 3-year longitudinal study of 345 high school students aged 11–19 years. Students performed curl-ups, push-ups and 20-m shuttle run tests from Fitnessgram. PA and ST were evaluated using a standard questionnaire. Standardized scores of fitness tests were summed. Changes over time were calculated as Δ₁ (2007 minus 2006), Δ₂ (2008 minus 2007) and Δ₃ (2008 minus 2006).
Results:  Changes in PAI were positively and independently associated with changes in fitness in Δ₁, Δ₂ and Δ₃. Changes in BMI were negatively associated with changes in fitness in Δ₃. Participants highly fit at baseline were those who showed positive changes in PAI over Δ₃, decreased changes in ST and had the lowest increase in BMI over 3 years compared with those low-fit at baseline.
Conclusions:  Changes in BMI were associated with changes in fitness over 3 years. However, changes in PAI were the best predictor for changes in fitness in each year and over the 3 years of evaluation in youth.     

Human mast cells derived from fetal liver cells cultured with stem cell factor express a functional CD51/CD61 (alpha v beta 3) integrin

Human fetal livers contain progenitor cells that become mast cells after 4 weeks of culture with recombinant human stem cell factor. Expression of cell surface CD29 (beta 1), CD18 (beta 2), CD61 (beta 3), and beta 5 integrins was investigated on such cells by flow cytometry and adhesion measurements. High surface expression of CD49e, CD51, and CD61 along with kit was apparent by 4 weeks of culture, whereas expression of each at day 0 was low to undetectable. CD29 and CD49d were detected on cells from day 0 to 4 weeks of culture; CD49b, CD49c, CD49f, CD18, and CD54 expression was negligible. The fetal liver- derived mast cells spontaneously adhered to vitronectin. No evidence for degranulation was found during vitronectin-dependent adhesion. Adhesion occurred in part through the CD61/CD51 receptor. No evidence for adhesion to vitronectin through CD29 and beta 5 integrins was obtained. Almost all of the vitronectin-adherent cells expressed CD51, CD61, kit, and tryptase, and exhibited metachromasia with toluidine blue. Thus, among the fetal liver-derived cells, developing mast cells were selectively adherent to vitronectin. These mast cells and the other cell types present also adhere spontaneously to fibronectin and to laminin, this adhesion being partially inhibited by antibodies against CD61 and CD29 integrins. In conclusion, human mast cells acquire functional vitronectin receptors as they develop from fetal liver progenitors under the influence of rhSCF. This may be important for the recruitment, localization, and retention of developing mast cells.     

Central nervous system disease in acquired immunodeficiency syndrome: prospective correlation using CT, MR imaging, and pathologic studies

A prospective study compared the abilities of high-resolution computed tomography (HRCT) and magnetic resonance (MR) imaging in detection and evaluation of central nervous system disease in neurologically symptomatic patients with acquired immunodeficiency syndrome (AIDS). Eighteen CT scans and 19 MR images in 14 patients were compared. HRCT images with contrast material enhancement were superior to unenhanced 0.35-T MR images for differentiating a lesion from surrounding edema, discriminating between lesions in close proximity, locating lesions for biopsy, judging lesion activity, detecting small cortical lesions with minimal edema, and spatial resolution. MR imaging was superior to CT scanning in evaluation of white-matter lesions and detection of small lesions surrounded by edema. MR imaging exhibited higher contrast resolution and greater sensitivity. Complementary uses of MR and CT imaging are suggested.     

哌拉西林钠／舒巴坦钠（2：1）体内抗菌活性研究

目的：评价哌拉西林钠／舒巴坦钠（2：1）的体内抗菌活性。方法：用产酶的金黄色葡萄球菌，大肠埃希菌、肺炎克雷伯菌及铜绿假单胞菌建立感染动物模型，用哌拉西林钠／舒巴坦钠（2：1）及单用派拉西林钠，舒巴坦钠及对照药阿莫西林钠／舒巴坦钠（2：1）通过静脉注射，皮下注射进行感染动物的治疗，评价对感染小鼠的保护作用。结果：舒巴坦钠对感染小鼠的抗菌保护作用极弱，ED50均＞400mg/kg，哌拉西林钠静脉注射单用对四种菌感染动物的ED50分别为55．7mg/kg,6.54mg/kg,24.09mg/kg与11．07mg/kg，哌拉西林钠／舒巴坦钠（2：1）者为27．96mg/kg，2.49mg/kg,6.75mg/kg与6.36mg/kg，分别比哌拉西林钠强2，2．5，3．6与1．8倍，哌拉西林钠皮下注射单用对四种菌感染动物的ED50分别为哌拉西林钠，哌拉西林钠／舒巴坦钠（2：1）皮下注射对四种产酶菌感染小鼠的保护作用弱于静脉注射者，ED50分别为51．95mg/kg,4.41mg/kg,8.19mg/kg,10.58mg/kg，但仍比哌拉西林钠强1．2，2，3．6与1．5倍。结论：无论静脉注射或皮下注射，哌拉西林钠／舒巴坦钠（2：1）对上述四种产酶菌株感染小鼠的体内抗菌活性（DE50）均明显优于哌拉西林钠，舒巴坦钠单用，也强于阿莫西林／舒巴坦钠（2：1）。静脉注射是临床应用较恰当的给药途径。     

Three-year multicenter surveillance of pneumococcal meningitis in children: clinical characteristics, and outcome related to penicillin susceptibility and dexamethasone use

OBJECTIVES: To evaluate the antibiotic susceptibility of Streptococcus pneumoniae isolates obtained from the blood and cerebrospinal fluid of children with meningitis. To describe and compare the clinical and microbiological characteristics, treatment, and outcome of children with meningitis caused by S pneumoniae based on antimicrobial susceptibility of isolates and the administration of dexamethasone. DESIGN AND PATIENTS: Children with pneumococcal meningitis were identified from among a group of patients with systemic infections caused by S pneumoniae who were enrolled prospectively in the United States Pediatric Multicenter Pneumococcal Surveillance Study at eight children's hospitals in the United States. From September 1, 1993 to August 31, 1996, 180 children with 181 episodes of pneumococcal meningitis were identified and data were collected by retrospective chart review. OUTCOME: Clinical and laboratory characteristics were assessed. All pneumococcal isolates were serotyped and antibiotic susceptibilities for penicillin and ceftriaxone were determined. Clinical presentation, hospital course, and outcome parameters at discharge were compared between children infected with penicillin-susceptible isolates and those with nonsusceptible isolates and for children who did and did not receive dexamethasone. RESULTS: Fourteen (7.7%) of 180 children died; none of the fatalities were because of a documented failure of treatment caused by a resistant strain. Only 1 child, who had mastoiditis and a lymphangioma, experienced a bacteriologic failure with a penicillin-resistant (minimum inhibitory concentration = 2 microgram/mL) organism. Of the 166 surviving children, 41 (25%) developed neurologic sequelae (motor deficits) and 48 (32%) of 151 children had unilateral (n = 26) or bilateral (n = 22) moderate to severe hearing loss at discharge. Overall, 12.7% and 6.6% of the pneumococcal isolates were intermediate and resistant to penicillin and 4.4% and 2.8% were intermediate and resistant to ceftriaxone, respectively. Clinical presentation, cerebrospinal fluid indices on admission, and hospital course, morbidity, and mortality rates were similar for patients infected with penicillin- or ceftriaxone-susceptible versus nonsusceptible organisms. However, the relatively small numbers of nonsusceptible isolates and the inclusion of vancomycin in the treatment regimen for the majority of the patients limit the power of this study to detect significant differences in outcome between patients infected with susceptible and nonsusceptible isolates. Nonetheless, our results show that the nonsusceptible organisms do not seem to be intrinsically more virulent. Forty children (22%) received dexamethasone (>/=8 doses) initiated before or within 1 hour after the first dose of antibiotics. The incidence of any moderate or severe hearing loss was significantly higher in the dexamethasone group (46%) compared with children not receiving any dexamethasone (23%). The incidence of any neurologic deficits, including hearing loss, also was significantly higher in the dexamethasone group (55% vs 33%). However, children in the dexamethasone group more frequently required intubation and mechanical ventilation and had lower initial concentration of glucose in the cerebrospinal fluid than children who did not receive any dexamethasone. When we controlled for the confounding factor, severity of illness (intubation), the incidence of any deafness and of any neurologic sequelae, including deafness, were no longer significantly different between children who did or did not receive dexamethasone. CONCLUSIONS: Children with pneumococcal meningitis caused by penicillin- or ceftriaxone-nonsusceptible organisms and those infected by susceptible strains had similar clinical presentation and outcome. The use of dexamethasone was not associated with a beneficial effect in this retrospective and nonrandomized study. (ABSTRACT TRUNCATED)     

Second‐line treatment in the Malawi antiretroviral programme: high early mortality,but good outcomes in survivors,despite extensive drug resistance at baseline*

Objectives

The Malawi antiretroviral therapy (ART) programme uses the public health approach to identify ART failure. Advanced disease progression may occur before switching to second‐line ART. We report outcomes for patients evaluated and initiated on second‐line treatment in Malawi.

Methods

Patients meeting Malawi immunological or clinical criteria for ART failure in two large urban ART clinics were evaluated for virological failure (viral load >400 HIV‐1 RNA copies/mL) and, if failure was confirmed, initiated on second‐line ART (zidovudine/lamivudine/tenofovir/lopinavir/ritonavir). Patients were seen monthly and laboratory evaluations were performed quarterly and as needed. We performed logistic regression modelling to identify factors associated with mortality, mortality or new HIV illnesses, and virological suppression at 12 months.

Results

Of the 109 patients with confirmed virological failure, five patients died prior to initiation, three declined switching and 101 patients initiated second‐line treatment. Over 12 months, 10 additional patients died, 34 patients experienced 45 HIV‐related events, and 19 patients experienced grade 3 or 4 toxicities. Among survivors, 85.2% had HIV‐1 RNA<400 copies/mL at 12 months. While power to distinguish differences was limited, response rates were similar regardless of baseline resistance level. The median CD4 count increase was 142 cells/μL. World Health Organization clinical failure at baseline [odds ratio (OR) 3.47; 95% confidence interval (CI) 1.14–10.59] and body mass index <18.5 (OR 4.43; 95% CI 1.15–17.12) were risk factors for death. Baseline CD4 count <50 cells/μL was associated with increased risk for death or morbidity at 12 months (OR 2.57; 95% CI 1.01–6.52).

Conclusions

Second‐line treatment in Malawi was associated with substantial mortality, morbidity and toxicity but, among survivors, virological outcomes were favourable.     

Treatment of Diamond-Blackfan anemia with recombinant human interleukin- 3 [see comments]

This report describes the response of eighteen Diamond-Blackfan anemia (DBA) patients to recombinant human interleukin-3 (rhIL-3). rhIL-3 was administered subcutaneously once daily on an escalating dose schedule (0.5 to 10 micrograms/kg/d). The rhIL-3 dose was escalated every 21 days until erythroid response was attained, grade III or IV nonhematologic toxicity was observed, or the maximum rhIL-3 dose was reached. Four patients experienced clinically significant erythroid responses. Two of the responders were steroid-dependent and transfusion- independent, while two were steroid-independent and transfusion- dependent. Baseline clinical or laboratory parameters, in particular in vitro bone marrow erythroid progenitor assays, were not useful in predicting rhIL-3 response. rhIL-3 administered at 5 to 10 micrograms/kg/d was associated with an increase in total white blood cell count, secondary to increases in neutrophils, eosinophils, and lymphocytes. Patients experienced a dose-dependent elevation in absolute eosinophils across the entire dose range. Two of the responding patients remain on maintenance rhIL-3, without diminution of effect at 244 and 370 + days. rhIL-3 was discontinued in the other two responders, because of the development of deep venous thrombi.