Increased uptake of 111In-octreotide in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is characterized by an uncontrolled accumulation and activation of lung fibroblasts. A modulation of fibroblast activation has been observed in various systems with octreotide, a synthetic somatostatin analog with strong affinity for the somatostatin receptor subtype 2 (sst2). One aim of our study was to evaluate the expression of somatostatin receptors in the lungs of patients with IPF. A second aim was to evaluate the relationship between 111In-octreotide uptake and the effect of pulmonary fibrosis as assessed by lung function tests and parameters and by radiologic findings. METHODS: We investigated 11 patients with IPF, 6 patients with pulmonary fibrosis associated with systemic sclerosis (SSc), and 19 patients with disease not of the lung (control patients). The expression of somatostatin receptors was evaluated in vivo using 111In-octreotide scintigraphy. We evaluated the relationship between 111In-octreotide uptake and the activity of pulmonary fibrosis as assessed by lung function tests, bronchoalveolar lavage (BAL) cellularity, and high-resolution CT (HRCT) of the chest. Planar images and thoracic SPECT (24 h) were performed after injection of 222 MBq of 111In-octreotide. Lung uptake was quantified using the lung-to-background ratio (L/B). In addition, the expression of sst2 was evaluated in vitro, in frozen lung-tissue samples using autoradiography, and in human cultures of lung fibroblasts using a ligand-binding assay. RESULTS: Compared with lung uptake in control patients (median L/B, 1.25; range, 1.14-1.49), lung uptake was increased in all 11 IPF patients (median L/B, 2.63; range, 1.59-3.13; P < 0.001) and in 4 of 6 SSc patients (median L/B, 1.68; range, 1.42-2.16). The L/B was lower in SSc patients than in IPF patients (P = 0.011). Increased uptake correlated with the alteration of lung function (carbon monoxide diffusing capacity [rho = -0.655; P = 0.038], diffusing capacity for carbon monoxide and alveolar volume ratio [rho = -0.627; P = 0.047], vital capacity [rho = -0.609; P = 0.054], and total lung capacity [rho = -0.598; P = 0.058]) and with the intensity of alveolitis (total BAL cellularity [rho = 0.756; P = 0.045], neutrophil counts [rho = 0.738; P = 0.05]), and HRCT fibrosis score (rho = 0.673; P = 0.007). Autoradiography suggested that vascular structures were a prominent binding site. Lung fibroblasts expressed somatostatin receptors in vitro as measured by binding assay. CONCLUSION: Our preliminary results identified an increased expression of sst2 in (mainly idiopathic) pulmonary fibrosis. Lung uptake correlates with the alteration of lung function and with the intensity of alveolitis.

Comparison of delayed gadolinium enhanced MRI of cartilage (dGEMRIC) using inversion recovery and fast T1 mapping sequences

The delayed Gadolinium Enhanced MRI of Cartilage (dGEMRIC) technique has shown promising results in pilot clinical studies of early osteoarthritis. Currently, its broader acceptance is limited by the long scan time and the need for postprocessing to calculate the T1 maps. A fast T1 mapping imaging technique based on two spoiled gradient echo images was implemented. In phantom studies, an appropriate flip angle combination optimized for center T1 of 756 to 955 ms yielded excellent agreement with T1 measured using the inversion recovery technique in the range of 200 to 900 ms, of interest in normal and diseased cartilage. In vivo validation was performed by serially imaging 26 hips using the inversion recovery and the Fast 2 angle T1 mapping techniques (center T1 756 ms). Excellent correlation with Pearson correlation coefficient R2 of 0.74 was seen and Bland-Altman plots demonstrated no systematic bias.

Reconstruction of the palatal aponeurosis with autogenous fascia lata in secondary radical intravelar veloplasty: a new method

Velopharyngeal insufficiency in cleft patients with muscular insufficiency detected by nasendoscopy is commonly treated by secondary radical intravelar veloplasty, in which the palatal muscles are reoriented and positioned backwards. The dead space between the retro-displaced musculature and the posterior borders of the palatal bone remains problematic. Postoperatively, the surgically achieved lengthening of the soft palate often diminishes due to scar tissue formation in the dead space, leading to reattachment of the reoriented muscles to the palatal bone and to decreased mobility of the soft palate. To avoid this, the dead space should be restored by a structure imitating the function of the missing palatal aponeurosis. The entire dead space was covered using a double layer of autogenous fascia lata harvested from the lateral thigh, which should allow sufficient and permanent sliding of the retro-positioned musculature. A clinical case of a 9-year-old boy who underwent the operation is reported. Postoperatively, marked functional improvements were observable in speech assessment, nasendoscopy and nasometry. The case reported here suggests that the restoration of the dead space may be beneficial for effective secondary palatal repair. Fascia lata seems to be a suitable graft for this purpose.

High failure rate of trochanteric fracture osteosynthesis with proximal femoral locking compression plate

INTRODUCTION Stable reconstruction of proximal femoral (PF) fractures is especially challenging due to the peculiarity of the injury patterns and the high load-bearing requirement. Since its introduction in 2007, the PF-locking compression plate (LCP) 4.5/5.0 has improved osteosynthesis for intertrochanteric and subtrochanteric fractures of the femur. This study reports our early results with this implant. METHODS Between January 2008 and June 2010, 19 of 52 patients (12 males, 7 females; mean age 59 years, range 19-96 years) presenting with fractures of the trochanteric region were treated at the authors' level 1 trauma centre with open reduction and internal fixation using PF-LCP. Postoperatively, partial weight bearing was allowed for all 19 patients. Follow-up included a thorough clinical and radiological evaluation at 1.5, 3, 6, 12, 24, 36 and 48 months. Failure analysis was based on conventional radiological and clinical assessment regarding the type of fracture, postoperative repositioning, secondary fracture dislocation in relation to the fracture constellation and postoperative clinical function (Merle d'Aubigné score). RESULTS In 18 patients surgery achieved adequate reduction and stable fixation without intra-operative complications. In one patient an ad latus displacement was observed on postoperative X-rays. At the third month follow-up four patients presented with secondary varus collapse and at the sixth month follow-up two patients had 'cut-outs' of the proximal fragment, with one patient having implant failure due to a broken proximal screw. Revision surgeries were performed in eight patients, one patient receiving a change of one screw, three patients undergoing reosteosynthesis with implantation of a condylar plate and one patient undergoing hardware removal with secondary implantation of a total hip prosthesis. Eight patients suffered from persistent trochanteric pain and three patients underwent hardware removal. CONCLUSIONS Early results for PF-LCP osteosynthesis show major complications in 7 of 19 patients requiring reosteosynthesis or prosthesis implantation due to secondary loss of reduction or hardware removal. Further studies are required to evaluate the limitations of this device.

True aneurysm of the peripheral pulmonary artery due to necrotizing giant cell arteritis

Pulmonary artery aneurysm in adults is a rare diagnosis. Most cases described in the literature are either associated with congenital heart disease or pulmonal arterial hypertension, respectively, or are not true aneurysms but rather pseudoaneurysms, which are usually iatrogenic. We present the case of a 68-year old female patient with the incidental finding of a true aneurysm of the right peripheral pulmonary artery with a maximum diameter of 4 cm. With increasing aneurysm diameter over time, the decision for a surgical resection was made. Complete resection of the aneurysm including lower lobe resection was performed. Histopathological examination showed necrotizing giant cell arteritis as the underlying cause. The postoperative course was uneventful and no signs of further disease activity were detected. To our knowledge, this is the first reported case of a pulmonary artery aneurysm caused by giant cell arteritis, whereas it should be noted that the distinction between Takayasu arteritis and giant cell arteritis is not clearly defined. Considering the high mortality associated with aneurysm rupture, surveillance is advocated for small aneurysms, whereas for larger aneurysms and those showing signs of progression in size despite medical therapy or even dissection, surgical intervention should be considered.

Analysis of mutations in $\beta$-tubulin genes affecting tubulin stability and assembly

Cmd4 is a colcemid-sensitive CHO cell line that is temperature sensitive for growth and expresses an altered $\beta$-tubulin, $\beta\sb1$. One revertant of this cell line, D2, exhibits a further alteration in $\beta\sb1$ resulting in an acidic shift in its isoelectric point and a decrease in its molecular weight to 40 kD, as measured by two dimensional gel electrophoresis. This $\beta$-tubulin variant has been shown to be assembly-defective and unstable. Characterization of the mutant $\beta\sb1$ in D2 by high pressure liquid chromatography (HPLC) revealed the loss of methionine containing tryptic peptides 7,8,9, and 10. Southern analysis of the genomic DNA digested with several different restriction enzymes resulted in the appearance of new restriction fragments 250 base pairs shorter than the corresponding fragments from the wild-type $\beta\sb1$-tubulin gene. Northern analysis on mRNA from D2 revealed two new message products that also differed by 250 bases from the corresponding wild type $\beta$-tubulin transcripts. To precisely define the region of the alteration, cloning and sequencing of the mutant and wild type genomic $\beta$-tubulin genes were conducted. A size-selected EcoRI genomic library was prepared using the Stratagene lambda Zap II phage cloning system. Using subclones of CHO $\beta$-tubulin cDNA as probes, a 2.5 kb wild type clone and a 2.3 kb mutant clone were identified from this library. Each of these was shown to contain a portion of the gene extending from intron 3 through the end of the coding sequence in exon 4 and into the 3$\sp\prime$ untranslated region on the basis of alignment with the published human $\beta$-tubulin sequence. Sequencing of the mutant 2.3 kb clone revealed that the mutation is due to a 246 base pair internal deletion in exon 4 (base pair 756-1001) that encodes amino acids 253-334. This deletion results in the loss of a putative binding site for GTP which could potentially explain the phenotype of this mutant $\beta$-tubulin. Also sequence comparison of the 3$\sp\prime$ untranslated region between different species revealed the conservation of 200 base pairs with 78% homology. It is proposed that this region could play an important role in the regulation of $\beta$-tubulin gene expression. ^