3D tumour spheroids as a model to assess the suitability of [18F]FDG-PET as an early indicator of response to PI3K inhibition

Background[18F] Fluorodeoxyglucose Positron Emission Tomography ([18F]FDG-PET) is widely used to monitor response to therapy in the clinic and has, more recently, been proposed as an early marker of long term response. This relies on the assumption that a change in glucose consumption parallels a reduction in viability and long term growth potential. However, cells may utilise substrates other than glucose and as many therapeutics interfere with glucose metabolism directly, it is entirely plausible that a positive [18F]FDG-PET response may be unrelated to long term growth. Furthermore, changes in metabolism and proliferation may take place on different temporal scales, thus restricting the time window in which [18F]FDG-PET is predictive. The PI3K oncogenic signalling pathway is a master regulator of multiple cellular processes including glucose metabolism, proliferation and cell survival. Inhibition of PI3K has been shown to reduce [18F]FDG uptake in several tumour types but the relative influence of this pathway on glucose metabolism and proliferation is not fully established.AimWe proposed to (i) assess the suitability of [18F]FDG as a tracer for measuring response to PI3K inhibition and (ii) determine the optimum imaging schedule, in vitro. We used multicellular tumour spheroids, an excellent 3D in vitro model of avascular tumours, to investigate the effects of the PI3K inhibitors, NVP-BKM120 and NVP-BEZ235, on [18F]FDG uptake and its relation to 3D growth.MethodsSpheroids were prepared from two cell lines with a constitutively active PI3K/Akt pathway, EMT6 (highly proliferative mouse mammary) and FaDu (moderately proliferate human nasopharyngeal). Treatment consisted of a 24 h exposure to either inhibitor, and growth was monitored over the following 7 days. To mimic potential imaging regimens with [18F]FDG-PET, average [18F]FDG uptake per viable cell was measured (a) directly following the 24 h exposure, (b) following an additional 24 h recovery period, or (c) following a 48 h exposure.ResultsGrowth was restricted significantly (p < 0.0001) in a dose-dependent fashion in spheroids from both cell lines treated with either inhibitor. In the highly proliferative cell line EMT6, [18F]FDG uptake was significantly reduced at all concentrations of inhibitor. For the moderately proliferative cell line FaDu, [18F]FDG was affected in a dose-dependent fashion, but to lesser degree. To assess the predictivity of [18F]FDG uptake for long term growth restriction, Pearson correlation coefficients were calculated for each imaging regimen. These indicated that the optimal imaging schedules differed between cell lines.ConclusionThis study suggests that [18F]FDG may be a suitable marker of response to PI3K inhibition in the cell lines that we have studied. Our data support the hypothesis that imaging schedules should be optimised on a tumour type-specific basis.     

Effect of shoulder girdle strengthening on trunk alignment in patients with stroke

[Purpose] This study investigated the effect of shoulder girdle strengthening, particularly the scapular muscles, on poststroke trunk alignment. [Subjects and Methods] The study involved 30 patients with residual hemiparesis following cerebrovascular stroke. Patient assessment included measuring shoulder muscle peak torque, scapular muscles peak force, spinal lateral deviation angle, and motor functional performance. Patients were randomly allocated either to the control group or the study group and received an 18-session strengthening program including active resisted exercises for shoulder abductors and external rotators in addition to trunk control exercises. The study group received additional strengthening exercises for the scapular muscles. [Results] The two groups showed significant improvement in strength of all shoulder and scapular muscles, with higher improvement in the study group. Similarly, the lateral spinal deviation angles significantly improved in both groups, with significantly higher improvement in the study group. Transfer activity, sitting balance, upper limb functions, and hand movements significantly improved in the two groups, with higher improvement in the latter two functions in the study group. [Conclusion] Strengthening of shoulder girdle muscles, particularly scapular muscles, can significantly contribute to improving the postural alignment of the trunk in patients with poststroke hemiparesis.Key words: Stroke, Scapular muscles strengthening, Lateral trunk alignment     

Laparoscopic cholecystectomy in the grossly obese: 4 years experience and review of literature

BackgroundConventional abdominal surgery in grossly obese patients is associated with an increased rate of postoperative complications; thus, laparoscopic surgery may be preferred in these patients.Patients and methodsA prospective analysis was performed of 20 grossly obese patients who underwent laparoscopic cholecystectomy between April 1996 and April 2000 for symptomatic non-complicated gallstone disease.ResultsTechnical problems at operation included difficulty with induction of pneumoperitoneum and introduction of the most lateral subcostal port, retraction of the gallbladder fundus, the need for longer instruments and the closure of the fascia. Laparoscopic cholecystectomy was successfully completed in 19 patients, but one patient required conversion to open operation. There were no anaesthetic difficulties. Two patients developed minor chest infections. The mean hospital stay was 2.9 days.ConclusionLaparoscopic cholecystectomy is feasible and can be recommended for symptomatic gallstone disease in grossly obese patients.     

Impact of Mild versus Moderate Intensity Aerobic Walking Exercise Training on Markers of Bone Metabolism and Hand Grip Strength in Moderate Hemophilic A Patients

Background

Patients with hemophilia A have low bone density than healthy controls. It is now widely recognized that physical activity and sports are beneficial for patients with hemophilia.

Objective

To compare the effects of mild and moderate intensity treadmill walking exercises on markers of bone metabolism and hand grip strength in male patients with moderate hemophilia A.

Material and Methods

Fifty male patients with moderate hemophilia, and age range from 25 to 45 years. The subjects were randomly assigned into 2 equal groups; the first group (A) received moderate intensity aerobic exercise training. The second group (B) received mild intensity aerobic exercise training.

Results

There was a 32.1% and 24.8% increase in mean values of serum calcium and hand grip strength respectively and 22.7 % reduction in mean values of parathyroid hormone in moderate exercise training group (A). While there was a 15.1 % and 15 % increase in mean values of Serum Calcium and Hand grip strength respectively and 10.3 % reduction in mean values of parathyroid hormone in mild exercise training group(B). The mean values of serum calcium and hand grip strength were significantly increased, while the mean values of parathyroid hormone were significantly decreased in both groups . There were significant differences between mean levels of the investigated parameters in group (A) and group (B) after treatment.

Conclusion

Moderate intensity aerobic exercise training on treadmill is appropriate to improve markers of bone metabolism and hand grip strength in male patients with hemophilia A.     

Recurrent supraventricular tachycardias prevalence and pathophysiology after RF ablation: A 5-year registry

Background

The introduction of technique of radiofrequency (RF) catheter ablation in 1990, has revolutionized management of different types of paroxysmal supraventricular tachycardia (PSVT). In spite of higher success rate, there were reported recurrences among different types of SVT. The aim of this study was to report the efficacy of RF ablation, its complications, recurrence rate and its predictors.

Methods

The material of this study (our 3rd registry) included patients who underwent electrophysiological study (EPS) and radiofrequency ablation of their supraventricular tachycardia in the past 5 years, starting from January 2002 to January 2007 at The Critical Care Medicine Department, Cairo University.

Results

Out of 400 pts studied, 381 (95%) had been subjected to radiofrequency ablation (RF) ablation while the remaining 19 pts (4.7%) refused ablation for fear of possible complications. Out of the 381 pts, 366 (96%) had their target tachycardia successfully terminated, from them 26 pts (7%) experienced recurrence after having successful RF ablation. Nine pts (34.6%) of total recurrence was reported in pts with AVNRT, 7 pts (26.9%) of total recurrence was reported in pts with AVRT utilizing septal accessory pathway (Rt AS and /or Rt PS AP), 4 pts (15.4%) was reported in pts with double AP, 2 pts (7.7%) of total recurrence was reported in pts with AFl, one pt (3.8%) of total recurrence was reported in cases of AT. Redo ablation have been carried out successfully in 25 pts (96.2%), and one pt (3.8%) refused ablation for fear of possible complications.

Conclusions

Although electrophysiological study and RF ablation eliminated different types of SVT. However, there may be increased incidence of recurrence among pts with AVNRT and AVRT utilizing concealed septal AP and multiple APs secondary to the complexity of AVN physiology, the critical location of septal AP, the clinical expertise, and poor electrophysiological criteria for good procedural success.     

Serum growth differentiation factor-15 (GDF-15) level in behcet's disease patients: Relation to clinical characteristics,musculoskeletal ultrasound findings and disease activity

Aim of the workThis study was conducted to assess serum level of growth differentiation factor-15(GDF-15) in Behcet’s disease (BD) patients and its relationship with clinical characteristics, ultrasound findings and disease activity.Patients and methodsStudy included 30 BD patients and 20 matched healthy controls. Visual analog scale (VAS)-pain of affected joints and Behcet’s disease current activity form (BDCAF) were assessed. The most affected joints and surrounding soft tissues were assessed by musculoskeletal ultrasound (MSUS).Serum GDF-15 level was measured.ResultsPatients were 23 males and 7 females (M:F 3.3:1) with a mean age of 34.6 ± 8.6 years and mean disease duration of 6.6 ± 4.5 years. 18(60%) had arthritis and arthralgia. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were 26.2 ± 21.2 mm/1^sthr and 50.4 ± 37 mg/dl respectively. There was significant increase of GDF-15 levels in patients with articular affection (3492.3 ± 4618.8 ng/ml) compared to those without (338.9 ± 90.3 ng/ml) and controls (322 ± 78.8 ng/ml) (p < 0.001).As regard MSUS, knee (n = 8) and ankle joints (n = 8) were the most commonly affected joints. Synovitis was present in 13 patients, enthesopathy was present in 10. GDF-15 significantly correlated with ESR and CRP (r = 0.48;p = 0.008 and r = 0.73, p = 0.005) and both remained significant on regression analysis that ESR (p = 0.019 and p = 0.007 respectively). At a serum GDF-15 cut-off point of 570 ng/ml for patients with peripheral arthritis/arthralgia the sensitivity and specificity were 88.9% and 91.7% respectively.ConclusionSerum GDF-15 can be used as a marker for articular affection in BD patients and is associated with the MSUS imaging visualizing subclinical inflammatory changes.     

CT findings of fungal pneumonia with emphasis on aspergillosis

Fungal pneumonias are increasingly common in the population of immunosuppressed patients. The diagnosis of fungal pneumonias represents a challenge for clinicians, and the morbidity and mortality of these infections are high in immunocompromised patients. CT findings may be nonspecific; however, in the appropriate clinical setting, they may suggest and even help establish the specific diagnosis. This article provides an overview about the CT findings and possible differential diagnosis of the most common pulmonary fungal infections.