A Dutch guideline for the treatment of scoliosis in neuromuscular disorders

Background

Children with neuromuscular disorders with a progressive muscle weakness such as Duchenne Muscular Dystrophy and Spinal Muscular Atrophy frequently develop a progressive scoliosis. A severe scoliosis compromises respiratory function and makes sitting more difficult. Spinal surgery is considered the primary treatment option for correcting severe scoliosis in neuromuscular disorders. Surgery in this population requires a multidisciplinary approach, careful planning, dedicated surgical procedures, and specialized after care.

Methods

The guideline is based on scientific evidence and expert opinions. A multidisciplinary working group representing experts from all relevant specialties performed the research. A literature search was conducted to collect scientific evidence in answer to specific questions posed by the working group. Literature was classified according to the level of evidence.

Results

For most aspects of the treatment scientific evidence is scarce and only low level cohort studies were found. Nevertheless, a high degree of consensus was reached about the management of patients with scoliosis in neuromuscular disorders. This was translated into a set of recommendations, which are now officially accepted as a general guideline in the Netherlands.

Conclusion

In order to optimize the treatment for scoliosis in neuromuscular disorders a Dutch guideline has been composed. This evidence-based, multidisciplinary guideline addresses conservative treatment, the preoperative, perioperative, and postoperative care of scoliosis in neuromuscular disorders.     

Overdiagnosis of asthma in obese and nonobese adults

Background

It is unclear whether asthma is overdiagnosed in developed countries, particularly among obese individuals, who may be more likely than nonobese people to experience dyspnea.

Methods

We conducted a longitudinal study involving nonobese (body mass index 20–25) and obese (body mass index ≥ 30) individuals with asthma that had been diagnosed by a physician. Participants were recruited from 8 Canadian cities by means of random-digit dialing. A diagnosis of current asthma was excluded in those who did not have evidence of acute worsening of asthma symptoms, reversible airflow obstruction or bronchial hyperresponsiveness, despite being weaned off asthma medications. We stopped asthma medications in those in whom a diagnosis of asthma was excluded and assessed their clinical outcomes over 6 months.

Results

Of 540 individuals with physician-diagnosed asthma who participated in the study, 496 (242 obese and 254 nonobese) could be conclusively assessed for a diagnosis of asthma. Asthma was ultimately excluded in 31.8% (95% confidence interval [CI] 26.3%–37.9%) in the obese group and in 28.7% (95% CI 23.5%–34.6%) in the nonobese group. Overdiagnosis of asthma was no more likely to occur among obese individuals than among nonobese individuals (p = 0.46). Of those in whom asthma was excluded, 65.5% did not need to take asthma medication or seek health care services because of asthma symptoms during a 6-month follow-up period.

Interpretation

About one-third of obese and nonobese individuals with physician-diagnosed asthma did not have asthma when objectively assessed. This finding suggests that, in developed countries such as Canada, asthma is overdiagnosed.Between 1980 and 1994, the age-adjusted prevalence of asthma increased by 75% in Canada and the United States.^1,2 The prevalence of both the symptoms and diagnosis of asthma may depend heavily on an awareness of asthma in the population studied.³ In recent decades, awareness of asthma has increased significantly among patients and their physicians. Part of this awareness has been stimulated by the medical community and part by the pharmaceutical industry, which has developed new medications for asthma and has directly or indirectly advertised these medications to patients and health care providers.³ In Scotland, the proportion of children reporting asthma symptoms who received a diagnosis of asthma from their physicians increased from 28% in 1964 to 64% in 1999.⁴ Part of the increase in prevalence may be attributable to changes in diagnostic labelling.Over the past 3 decades, the incidence and prevalence of obesity has increased concurrently with the incidence and prevalence of asthma, which indicates a possible link between obesity and asthma.^5–7 Studies have suggested that asthma is almost twice as likely to be diagnosed in obese people as in nonobese people. In Canada and the United States, 8.8%–9.2% of obese adults reported having received a diagnosis of asthma from a physician, as compared with 4%–5% of nonobese adults.^8,9It is unclear whether this increased tendency to diagnose asthma in patients with respiratory symptoms is appropriate, or whether asthma may be overdiagnosed in developed countries. Potential overdiagnosis of asthma may be even more pronounced among obese people. Obesity decreases chest wall compliance, which results in reduced lung volumes, increased work of breathing and increased energy and oxygen costs of breathing.^10–12 Because obese patients report more dyspnea and asthma-like symptoms than nonobese patients, they may be more likely to be misdiagnosed by their physicians as having asthma.We conducted this study to determine the proportion of obese and nonobese Canadian adults who have an incorrect diagnosis of asthma. We also assessed whether overdiagnosis of asthma was more prevalent among obese than among nonobese individuals. Finally, we determined what proportion of obese and nonobese patients could safely discontinue their asthma medications once a diagnosis of asthma was excluded.     

Long acting β2 agonists for stable chronic obstructive pulmonary disease with poor reversibility: a systematic review of randomised controlled trials

Background

The long acting β2-agonists, salmeterol and formoterol, have been recommended, by some, as first line treatment of stable chronic obstructive pulmonary disease (COPD). We reviewed evidence of efficacy and safety when compared with placebo or anticholinergic agents in patients with poorly reversible COPD.

Methods

After searching MEDLINE, EMBASE, HealthSTAR, BIOSIS Previews, PASCAL, ToxFile, SciSearch, the Cochrane Library, and PubMed, as well as Web sites, selected journals, reference lists, and contacting drug manufacturers, two reviewers independently screened reports of randomised controlled trials of parallel or crossover design lasting four weeks or longer and including patients with a forced expiratory volume in one second (FEV1) ≤ 75% of predicted, a ratio of FEV1 to forced vital capacity (FVC) ≤ 88% of predicted, and < 15% improvement from baseline FEV1 after a dose of a β2 agonist. We included trials comparing salmeterol or formoterol with placebo or with ipratropium bromide and reporting one of these outcomes: lung function; exercise capacity; quality of life scores; dyspnea; exacerbations; rescue inhaler use; incidence of tachycardia, hypokalemia, or dry mouth. Two reviewers assessed the quality of included reports using the Jadad scale and allocation concealment, and abstracted data.

Results

Twelve trials satisfied our inclusion criteria; eight were high quality (Jadad score >2) and four were low quality (≤ 2). The adequacy of allocation concealment was unclear in all of them. We did not perform a meta-analysis due to differences in trial design and how outcomes were reported. Two trials comparing salmeterol with ipratropium did not detect differences; one trial comparing formoterol and ipratropium described greater improvement with formoterol in morning PEFR (15.3 versus 7.1 l/min, p = 0.040). Of twelve trials comparing long acting β2 agonists with placebo, six reported no improvement in exercise capacity, eleven reported improvements in FEV1 lung function (one reported no improvement), six reported less rescue inhaler usage (one reported no difference) and five reported improved dyspnea scores (two reported no improvement). Differences in quality of life were detected in one salmeterol trial ; however, two salmeterol, and one formoterol trial reported no differences. Adverse effects of interest were not reported.

Conclusion

In terms of clinical outcomes and safety, we could not find convincing evidence that salmeterol and formoterol have demonstrated advantages to ipratropium, a less expensive drug, for patients with stable COPD and poor reversibility. Compared to placebo, we found evidence of reduced rescue inhaler usage and improved spirometric outcomes without a significant impact on quality of life or exercise capacity.     

Male preponderance in early diagnosed type 2 diabetes is associated with the ARE insertion/deletion polymorphism in the <Emphasis Type="Italic">PPP1R3A</Emphasis> locus

Background  

The ARE insertion/deletion polymorphism of PPP1R3A has been associated with variation in glycaemic parameters and prevalence of diabetes. We have investigated its role in age of diagnosis, body weight and glycaemic control in 1,950 individuals with type 2 diabetes in Tayside, Scotland, and compared the ARE2 allele frequencies with 1,014 local schoolchildren.     

Crystal structure of human sex hormone-binding globulin: steroid transport by a laminin G-like domain

Human sex hormone-binding globulin (SHBG) transports sex steroids in blood and regulates their access to target tissues. In biological fluids, SHBG exists as a homodimer and each monomer comprises two laminin G-like domains (G domains). The crystal structure of the N-terminal G domain of SHBG in complex with 5alpha-dihydrotestosterone at 1.55 A resolution reveals both the architecture of the steroid-binding site and the quaternary structure of the dimer. We also show that G domains have jellyroll topology and are structurally related to pentraxin. In each SHBG monomer, the steroid intercalates into a hydrophobic pocket within the beta-sheet sandwich. The steroid and a 20 A distant calcium ion are not located at the dimer interface. Instead, two separate steroid-binding pockets and calcium-binding sites exist per dimer. The structure displays intriguing disorder for loop segment Pro130-Arg135. In all other jellyroll proteins, this loop is well ordered. If modelled accordingly, it covers the steroid-binding site and could thereby regulate access of ligands to the binding pocket.     

东南沿海部队皮肤浅部真菌病的调查研究

目的了解东南沿海部队官兵近年真菌菌种构成情况及调查浅部真菌病非高发季节的患病率。方法于11月对浙江地区和福建地区某部队官兵共324人进行浅部真菌病患病情况调查,通过临床检查确定皮肤病种类和感染人(次),对于临床诊断为浅部真菌病的官兵进行真菌镜检证实后明确诊断,并留菌种进行真菌培养。结果真菌感染性疾病患病率为55.2%(324人中179人发病),其中手足癣158人次(48.8%),体股癣35人次(10.8%),花斑癣24人次(7.4%),马拉色菌毛囊炎18人次(5.6%),甲癣5人次(1.5%)。真菌镜检阳性率为76.36%,首位致病菌为红色毛癣菌71株,占84.5%。结论部队尤其是亚热带地区部队,浅部真菌病的患病率较高,不同驻地官兵患皮肤浅部真菌病有差异,而服役年限及兵源与患皮肤浅部真菌病之间无显著差异。     

Aflatoxin contamination of rice in the United Arab Emirates

Many people in the United Arab Emirates store rice in large quantities for long periods of time before use. Five hundred samples of rice were collected from households in Al-Ain city during the summers of 1992-1994. Aflatoxin B₁ was detected in 160 samples (64%) of long grain rice and 81 Samples (32%) of short grain rice at levels ranging from 1.2 to 16.5 μg/kg. The moisture content of samples varied between 5.7% and 15.3%. Species ofAspergillus andPenicillium (includingA. flavus andA. parasiticus) were isolated from discoloured, broken and insect damaged grain and it was confirmed that at least two of the isolates ofA. flavus were aflatoxigenic. These findings demonstrate that rice may contribute to dietary exposure to aflatoxins which are known to be carcinogenic and immunosuppressive.     

鸡PPARγ基因的表达特性及其对脂肪细胞增殖分化的影响

为分析鸡PPARγ基因的组织表达特性及其在脂肪细胞增殖和分化过程中的功能,文章以东北农业大学高、低腹脂双向选择品系肉鸡为实验材料,利用Western blotting方法,检测PPARγ基因的组织表达特性及其在高、低脂系肉鸡腹部脂肪组织间的表达差异;采用RNAi技术,在鸡原代脂肪细胞中抑制PPARγ基因的表达后,通过MTT和油红O提取比色的方法,研究鸡PPARγ基因对脂肪细胞增殖和分化的调控作用;利用Real-timePCR和Western blotting技术,分析PPARγ基因表达下调后,其他脂肪细胞分化转录因子以及与脂肪细胞分化相关的重要基因的表达变化情况。结果表明,PPARγ基因在7周龄高脂系肉鸡腹部脂肪组织、肌胃、脾脏、肾脏组织中表达量较高,在心脏中表达量较低,在肝脏、胸肌、腿肌、十二指肠中未检测到表达信号;与高脂系相比,PPARγ基因在5和7周龄低脂系肉鸡腹部脂肪组织中的表达量较低(P<0.05);PPARγ基因的表达量下降后,鸡脂肪细胞的增殖能力增强,分化能力减弱;同时,C/EBPα、SREBP1、A-FABP、Perilipin1、LPL、IGFBP-2基因的表达量均下降(P<0.05)。由此可见,PPARγ基因的表达可能与肉鸡腹部脂肪的沉积有一定的关系,该基因可能是调控鸡脂肪细胞增殖与分化的关键因子。     

PtrWRKY51基因的克隆及抗旱表达特性分析

为明确毛果杨WRKY家族成员PtrWRKY51基因功能,以Nisqually-1株系毛果杨为模板,克隆得到PtrWRKY51基因CDS序列。通过生物信息学分析,结合酵母自激活验证、亚细胞定位及模拟干旱胁迫下的实时荧光定量PCR(qRT-PCR)对PtrWRKY51基因功能进行初步研究。结果表明：PtrWRKY51全长579 bp,编码192 aa。生物信息学分析及亚细胞定位试验结果表明,PtrWRKY51蛋白为非跨膜碱性不稳定亲水蛋白,定位于细胞核,含有WRKY家族特有的保守结构域,是第IIc类WRKY转录因子;酵母自激活验证试验表明PtrWRKY51基因具有自激活活性;qRT-PCR分析表明,8%PEG6000模拟干旱胁迫下,该基因在胁迫12 h后茎部与叶部相对表达量达到最大值,根部则出现在24 h,研究可为PtrWRKY51抗逆及生物学功能进一步研究提供参考。