Tamoxifen enhances the control of acromegaly treated with somatostatin analog lanreotide

We present the case of a 51-year old female patient with acromegaly that was resistant to somatostatin analogs and dopamine agonists. The patient was diagnosed with breast cancer requiring treatment with the anti-estrogen tamoxifen. Prior to initiating the treatment with tamoxifen, the IGF-I level was very high at 415% of the upper limit of normal for the patient’s age and sex. During the tamoxifen treatment, the level of IGF-I dropped spectacularly down to normal levels. This observation highlights the effect of an anti-estrogen treatment in certain female patients with acromegaly.     

Real frequency of ordinary and atypical sub-trochanteric and diaphyseal fractures in France based on X-rays and medical file analysis

PurposeAtypical sub-trochanteric and femoral shaft fractures have been reported in patients treated with bisphosphonates. Their incidence has been determined from registered data analysis using international codes. Therefore, the aim of our study was to estimate the real frequency of typical and atypical sub-trochanteric or diaphyseal fractures, based on radiological and clinical data compared to registered data.MethodsIn the registers of three large French University Hospitals, patients identified with International Classification of Diseases, 10th Revision diagnosis codes for sub-trochanteric or diaphyseal fracture were selected. Frequencies of ordinary and atypical fractures were calculated after both registered data, radiological and clinical files analysis.ResultsAmong the 4592 patients hospitalized for a femoral fracture over 5 years, 574 were identified to have had a sub-trochanteric or femoral shaft fracture. 47.7% of the sub-trochanteric and femoral shaft fractures were misclassified, predominantly in the sub-trochanteric fractures subset. 12 patients had an atypical fracture (4% of the sub-trochanteric and femoral shaft fractures) and 11 fractures presented radiological features of atypical fractures, whereas clinical files analysis revealed they were pathological or traumatic fractures.ConclusionAtypical fractures frequency is very low. Because of their low frequency and the unreliability of registered databases, the risk of atypical fractures is very difficult to estimate retrospectively. A prospective study is needed to clarify the risk factors associated with these fractures.     

A role for vesicular glutamate transporter 1 in synaptic vesicle clustering and mobility

Synaptic vesicles (SVs) from excitatory synapses carry vesicular glutamate transporters (VGLUTs) that fill the vesicles with neurotransmitter. Although the essential function of VGLUTs as glutamate transporters has been well established, the evidence for additional cell‐biological functions is more controversial. Both VGLUT1 and VGLUT2 disruptions in mice result in a reduced number of SVs away from release sites, flattening of SVs, and the appearance of tubular structures. Therefore, we analysed the morphology, biochemical composition and trafficking of SVs at synapses of VGLUT1^?/? mice in order to test for a function of VGLUTs in the formation or clustering of SVs. Analyses with high‐pressure freezing immobilisation and electron tomography pointed to a role of VGLUT1 transport function in the tonicity of excitatory SVs, explaining the aldehyde‐induced flattening of SVs observed in VGLUT1^?/? synapses. We confirmed the steep reduction in the number of SVs previously observed in VGLUT1^?/? presynaptic terminals, but did not observe accumulation of endocytotic intermediates. Furthermore, SV proteins of adult VGLUT1^?/? mouse brain tissue were expressed at normal levels in all subcellular fractions, suggesting that they were not displaced to another organelle. We thus assessed the mobility of the recently documented superpool of SVs. Synaptobrevin2–enhanced green fluorescent protein time lapse experiments revealed an oversized superpool of SVs in VGLUT1^?/? neurons. Our results support the idea that, beyond glutamate loading, VGLUT1 enhances the tonicity of excitatory SVs and stabilises SVs at presynaptic terminals.     

CT-Guided Percutaneous Gastrostomy without Preliminary Placement of a Nasogastric Tube

Percutaneous radiologic gastrostomy (PRG) requires preliminary gastric inflation through a nasogastric tube (NGT) to safely perform gastric puncture. However, in case of pharyngeal or esophageal obstruction, NGT placement may be impossible even with a hydrophilic angiography catheter and wire. This brief report describes percutaneous computed tomography (CT)–guided gastrostomy with a 2-stick approach without nasogastric insufflation in 13 patients. Technical success rate was 100% with a mean of 1.8 punctures ± 1.0 to access the gastric lumen. Traversal of the colon and liver with a 22-gauge needle was necessary in 4 and 1 patients, respectively. There were no major complications. Minor complications occurred in 6 patients (46%). CT-guided percutaneous gastrostomy is technically feasible with minimal morbidity.     

Inhaled phage therapy: a promising and challenging approach to treat bacterial respiratory infections

Introduction: Bacterial respiratory tract infections (RTIs) are increasingly difficult to treat due to evolving antibiotic resistance. In this context, bacteriophages (or phages) are part of the foreseen alternatives or combination therapies. Delivering phages through the airways seems more relevant to accumulate these natural antibacterial viruses in proximity to their bacterial host, within the infectious site.

Areas covered: This review addresses the potential of phage therapy to treat RTIs and discusses preclinical and clinical results of phages administration in this context. Recent phage formulation and aerosolization attempts are also reviewed, raising technical challenges to achieve efficient pulmonary deposition via inhalation.

Expert opinion: Overall, the inhalation of phages as antibacterial treatment seems both clinically relevant and technically feasible. Several crucial points still need to be investigated, such as phage product pharmacokinetics and immunogenicity. Furthermore, given phage-specific features, appropriate regulatory and manufacturing guidelines will need to be defined. Finally, randomized controlled clinical trials should be carried out to establish phage therapy’s clinical positioning in the antimicrobial arsenal against RTIs.     

Noninvasive quantitation of blood flow turbulence in patients with aortic valve disease using online digital computer analysis of Doppler velocity data.

Previous experimental studies have demonstrated that aortic valve disease is associated with significant downstream turbulence (T). In this study, we developed a noninvasive method on the basis of Doppler velocity recording for quantitating aortic blood flow T in patients with aortic valve disease. The instantaneous blood velocity at a point in the aorta is equal to the sum of a mean periodic velocity component with a random or turbulent velocity component. According to the ensemble average method, time mean absolute T intensity is the root-mean-square value of turbulent velocity averaged over time and T is better quantitated by the relative T intensity (TIr), which is the ratio of absolute T intensity to the ensemble average velocity averaged over time. We computed TIr in 18 patients with mild to severe aortic stenosis and in 13 healthy volunteers from instantaneous modal velocities of 70 cycle length-matched heart beats recorded in the proximal part of the descending aorta by pulsed Doppler using an ultrasound system with an output port for online digital data transfer into a microcomputer. TIr was greater in patients with aortic valve disease (18.4 +/- 5.1%, range 11.2%-28.9%) than in control patients (7.9 +/- 1.9%, range 4.8%-9.8%; P =.0001). In patients with aortic valve disease, TIr was better linearly related to the ratio of postvalvular aorta to valvular orifice cross-sectional areas (r = 0.89, P =.0001) than to other parameters of valve restriction: transvalvular pressure gradient (r = 0.78, P =.0001); valve area (r = -0.56, P =.01); and valve resistance (r = 0.72, P =.0002). Thus, T that can be computed noninvasively from direct digital transfer of Doppler velocity data appears to be linearly related to indices of aortic valve restriction. Our data support the concept of the postvalvular aorta to valvular orifice cross-sectional areas ratio as a new important hemodynamic parameter in patients with aortic valve disease.     

Serial elongation,derotation and flexion (EDF) casting under general anesthesia and neuromuscular blocking drugs improve outcome in patients with juvenile scoliosis: preliminary results

Purpose

Juvenile scoliosis (JS), among different types of spinal deformity, remains still a challenge for orthopedic surgeons. Elongation, derotation and flexion (EDF) casting technique is a custom-made thoracolumbar cast based on a three-dimensional correction concept. The primary objective of the present study was to measure changes on plain radiographs of patients with JS treated with EDF plaster technique. The second aim was to evaluate the effectiveness of the EDF plaster technique realized under general anesthesia (GA) and neuromuscular blocking drugs, i.e. curare, on the radiological curve correction.

Methods

A retrospective comparative case series study was performed in which were included forty-four skeletally immature patients. Three patient groups were selected. Group 1: EDF cast applied with patients awaken and no anesthesia; Group 2: EDF cast applied under GA without neuromuscular blocking drugs; Group 3: EDF cast applied under GA with neuromuscular blocking drugs. All the patients were treated with two serial EDF casts by 2 months and a half each. All measurements were taken from the radiographic exams. Cobb’s angle; RVAD and Nash and Moe grade of rotation were assessed before and after applying the cast. Thirty-four (77.3 %) patients were followed up at least 24 months after removal of last EDF cast.

Results

Eighteen patients (3 males, 15 females) were included in Group 1, 12 (2 males, 10 females) in Group 2 and 14 (5 males, 9 females) in Group 3. Serial EDF casting was more effective at initial curve reduction and in preventing curve progression when applied under GA with neuromuscular blocking drugs, i.e. curare. RVAD and Nash and Moe score improved significantly in all groups of patients treated according to principles of EDF technique. During follow-up period, six patients required surgery in Group 1 (6/18; 33.3 %), 3 patients required surgery in Group 2 (3/12; 25 %) and 2 patients underwent surgery in Group 3 (2/14; 15 %).

Conclusions

Preliminary results show EDF casting is effective in controlling the curve in both frontal (Cobb’s angle) and transverse plane (rib vertebral angle and apical vertebral rotation degree).