Incomplete rescue of cystic fibrosis transmembrane conductance regulator deficient mice by the human CFTR cDNA

We have used a mouse model to study the ability of human CFTR to correct the defect in mice deficient of the endogenous protein. In this model, expression of the endogenous Cftr gene was disrupted and replaced with a human CFTR cDNA by a gene targeted 'knock-in' event. Animals homozygous for the gene replacement failed to show neither improved intestinal pathology nor survival when compared to mice completely lacking CFTR. RNA analyses showed that the human CFTR sequence was transcribed from the targeted allele in the respiratory and intestinal epithelial cells. Furthermore, in vivo potential difference measurements showed that basal CFTR chloride channel activity was present in the apical membranes of both nasal and rectal epithelial cells in all homozygous knock-in animals examined. Ussing chamber studies showed, however, that the cAMP-mediated chloride channel function was impaired in the intestinal tract among the majority of homozygous knock-in animals. Hence, failure to correct the intestinal pathology associated with loss of endogenous CFTR was related to inefficient functional expression of the human protein in mice. These results emphasize the need to understand the tissue- specific expression and regulation of CFTR function when animal models are used in gene therapy studies.      

Ulnar procedures for post-traumatic disorders of the distal radioulnar joint

Post-traumatic abnormality of the distal radioulnar joint (DRUJ) still presents a therapeutic challenge to orthopaedic surgeons. The most common difficulty is a failure to diagnose these injuries early, resulting in chronic post-traumatic disorders of the DRUJ. The main aim of therapy is to avoid adverse sequelae. This is of particular importance in malunion of the distal radius, the most common cause for post-traumatic disorders of the DRUJ. Distal radial malunion can be avoided by early appropriate treatment and the need for subsequent ulnar procedures reduced. Ulnar procedures for post-traumatic disorders of the DRUJ are intended to improve function and to decrease pain. Many methods to improve post-traumatic DRUJ function have been described. This article reviews the current state of the art in dealing with post-traumatic disorders of the distal radioulnar joint and presents algorithms to help in decision making.     

原发性单侧症状帕金森病磁共振氢质子谱研究

目的:探讨磁共振氢质子谱(1H-MRS)对原发性单侧起病帕金森病的诊断价值。方法:未经治疗的原发单侧症状PD患者50例为PD组,健康人42名为对照组。两组分别予以双侧壳核MRS检查,由仪器自带软件自动计算得双侧壳核代谢物比值:NAA/Cr,Cho/Cr,NAA/Cho。结果:PD组患者其症状对侧壳核NAA/cr比值分别较同侧及健康对照组双侧壳核相应比值均值明显下降(分别为1.23±0.22,1.38±0.33,1.33±0.16;t=2.616,P=0.01和t=2.324,P=0.02),而其NAA/Cho、Cho/Cr比值较同侧及对照组相应比值均值无显著差异。症状同侧壳核NAA/cr、NAA/Cho、Cho/Cr较对照组无明显差异。结论:原发性单侧症状PD其症状的对侧壳核早期就可能存在神经元的缺失或胶质增生,提示壳核磁共振波谱分析可为早期PD的临床诊断提供较为可靠的客观依据。     

Multiple cerebral metastases: detectability with Gd-DTPA-enhanced MR imaging

Sixteen patients with suspected cerebral metastases were studied with magnetic resonance (MR) imaging before and after the intravenous administration of 0.1 mmol/kg of gadolinium diethylenetriaminepenta-acetic acid. The images were interpreted blindly by two neuroradiologists; all clinical, radiologic (computed tomographic and MR imaging), and pathologic data were reviewed to arrive at a final "best diagnosis," which was then compared with the prior blinded interpretations. Of seven patients found to have multiple metastases, six (86%) had at least one tumor nodule depicted by postinfusion MR imaging that was missed by one or both observers on review of preinfusion images alone. Lesions missed on preinfusion studies were usually small nodules hidden by or not detected next to regions of high-signal edema thought to be related to the adjacent tumor nodule. The authors believe that contrast enhancement improves detection of metastatic foci with MR imaging and that the findings indicate broader implications for the detection of multiple lesions from other causes.     

Digital radiography of subtle pulmonary abnormalities: an ROC study of the effect of pixel size on observer performance

Forty conventional radiographs with examples of mild interstitial infiltrates and subtle pneumothoraces and 40 normal studies of the chest were selected and digitized, with pixel sizes of 1.0, 0.5, 0.2, and 0.1 mm. Observer performance tests were carried out using receiver operating characteristic analysis. Conventional radiographs and digitized images were compared. The results indicate that, in such cases, diagnostic accuracy increases significantly as the pixel size is reduced, at least to the 0.1-mm level. We conclude that, for digital systems using screen-film or similar image receptors, use of a pixel size substantially larger than 0.1 mm may result in some loss of diagnostic accuracy.     

Ganglioneuroblastic Transformation in Olfactory Neuroblastoma

Ganglioneuroblastic transformation in olfactory neuroblastoma (ONB) is an exceptionally rare phenomenon. We document the case of a patient with a poorly differentiated sinonasal malignancy that recurred following treatment with chemoradiotherapy and showed ganglioneuroblastic transformation. Although the index tumour showed neuroendocrine differentiation, it did not have the typical clinico-pathological features associated with ONB. We highlight the diagnostic difficulties in establishing an accurate diagnosis for undifferentiated sinonasal tumours and present evidence that the index tumour was an ONB. The current report is only the third case of ONB showing complete ganglioneuroblastic transformation.     

Radial shortening following a fracture of the proximal radius

Background and purpose

The Essex-Lopresti lesion is thought to be rare, with a varying degree of disruption to forearm stability probable. We describe the range of radial shortening that occurs following a fracture of the proximal radius, as well as the short-term outcome in these patients.

Patients and methods

Over an 18-month period, we prospectively assessed all patients with a radiographically confirmed proximal radial fracture. Patients noted to have ipsilateral wrist pain at initial presentation underwent bilateral radiography to determine whether there was disruption of the distal radio-ulnar joint suggestive of an Essex-Lopresti lesion. Outcome was assessed after a mean of 6 (1.5–12) months using clinical and radiographic results, including the Mayo elbow score (MES) and the short musculoskeletal function assessment (SMFA) questionnaire. One patient with a Mason type-I fracture was lost to follow-up after initial presentation.

Results

60 patients had ipsilateral wrist pain at the initial assessment of 237 proximal radial fractures. Radial shortening of ≥ 2mm (range: 2–4mm) was seen in 22 patients (mean age 48 (19–79) years, 16 females). The most frequent mechanism of injury was a fall from standing height (10/22). 21 fractures were classified as being Mason type-I or type-II, all of which were managed nonoperatively. One Mason type-III fracture underwent acute radial head replacement. Functional outcome was assessed in 21 patients. We found an excellent or good MES in 18 of the 20 patients with a Mason type-I or type-II injury.

Interpretation

The incidence of the Essex-Lopresti lesion type is possibly under-reported as there is a spectrum of injuries, and subtle disruptions often go unidentified. A full assessment of all patients with a proximal radial fracture is required in order to identify these injuries, and the index of suspicion is raised as the complexity of the fracture increases.The Essex-Lopresti lesion is the eponym given to radio-ulnar instability caused by sequential injury to the distal radio-ulnar joint, the interosseous membrane, and fracture of the proximal radius (Essex-Lopresti 1951). The original paper by Essex-Lopresti suggested that this is a rare injury, with subsequent literature indicating that the lesion is present in approximately 1% of all radial head fractures (Essex-Lopresti 1951, Trousdale et al. 1992). A varying degree of force, in order to sustain such an injury, has been reported (Hotchkiss et al. 1989, Wallace et al. 1997).The diagnosis and treatment are challenging, with further imaging used when an unstable lesion is suspected (Starch and Dabezies 2001, Wallace 2002). When there is instability, open reduction and internal fixation or radial head replacement with added longitudinal stabilization of the forearm bones is recommended (Lewin 1973, Edwards and Jupiter 1988, Bruckner et al. 1996).A recent study has shown that the incidence of associated injuries following radial head fractures is high on MRI (Kaas et al. 2010). The purpose of our study was to describe the spectrum of radial shortening suggestive of an Essex-Lopresti lesion that occurs following a radial head or neck fracture, along with determining the short-term outcome in these patients.     

Unintended consequences of policy change to watchful waiting for asymptomatic inguinal hernias

Introduction

In 2009 the Department of Health instructed McKinsey & Company to provide advice on how commissioners might achieve world class National Health Service productivity. Asymptomatic inguinal hernia repair was identified as a potentially cosmetic procedure, with limited clinical benefit. The Birmingham and Solihull primary care trust cluster introduced a policy of watchful waiting for asymptomatic inguinal hernia, which was implemented across the health economy in December 2010. This retrospective cohort study aimed to examine the effect of a change in clinical commissioning policy concerning elective surgical repair of asymptomatic inguinal hernias.

Methods

A total of 1,032 patients undergoing inguinal hernia repair in the 16 months after the policy change were compared with 978 patients in the 16 months before. The main outcome measure was relative proportion of emergency repair in groups before and after the policy change. Multivariate binary logistic regression was used to adjust the main outcome for age, sex and hernia type.

Results

The period after the policy change was associated with 59% higher odds of emergency repair (3.6% vs 5.5%, adjusted odds ratio [OR]: 1.59, 95% confidence interval [CI]: 1.03–2.47). In turn, emergency repair was associated with higher odds of adverse events (4.7% vs 18.5%, adjusted OR: 3.68, 95% CI: 2.04–6.63) and mortality (0.1% vs 5.4%, p<0.001, Fisher’s exact test).

Conclusions

Introduction of a watchful waiting policy for asymptomatic inguinal hernias was associated with a significant increase in need for emergency repair, which was in turn associated with an increased risk of adverse events. Current policies may be placing patients at risk.     

Small Cell Neuroendocrine Carcinoma of the Oropharynx Harbouring Oncogenic HPV-Infection

Small cell carcinoma/neuroendocrine carcinoma (SCNEC) of the oropharynx is uncommon. Recently, an association has been reported between oropharyngeal SCNEC and high-risk human papillomavirus (HPV) infection. While HPV infection confers a better prognosis for oropharyngeal squamous cell carcinoma, HPV infection does not appear to influence the biological behaviour of SCNECs, which are generally associated with poor clinical outcomes. We document two cases of SCNEC arising in the oropharynx with evidence of high-risk HPV infection. The cases highlight the expanding range of malignant oropharyngeal neoplasms that harbour oncogenic HPV infection and support the concept that, irrespective of HPV infection, neuroendocrine differentiation portends a poor prognosis.