Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function.

Pooled results from 19 trials with 33 826 asthmatic participants found that long-acting β-agonists increased exacerbations requiring hospitalization and life-threatening exacerbations compared with...

Meta-Analysis: Effect of Long-Acting β-Agonists on Severe Asthma Exacerbations and Asthma-Related Deaths

Purpose We conducted a phase II study of combination of the anti–insulin-like growth factor 1 receptor antibody CP-751,871 with paclitaxel and carboplatin (PCI) in advanced treatment-naive non–small-cell lung cancer (NSCLC) Patients and Methods Patients were randomly assigned (2:1) to paclitaxel 200 mg/m2, carboplatin (area under the plasma concentration-time curve of 6), and CP-751,871 10 to 20 mg/kg (PCI10, PCI20) or paclitaxel and carboplatin alone (PC) every 3 weeks for up to six cycles PCI10-20 patients could continue CP-751,871 (figitumumab) treatment after chemotherapy discontinuation Patients treated with PC experiencing disease progression were eligible to receive CP-751,871 at investigator's discretion An additional nonrandomized single-arm cohort of 30 patients with nonadenocarcinoma tumor histology receiving PCI20 was enrolled on completion of the randomized study Results A total of 156 patients were enrolled onto the randomized portion of the study Safety and efficacy information are av

Phase II Study of the Anti–Insulin-Like Growth Factor Type 1 Receptor Antibody CP-751,871 in Combination With Paclitaxel and Carboplatin in Previously Untreated, Locally Advanced, or Metastatic Non–Small-Cell Lung Cancer

STUDY DESIGN A cross-sectional radiologic and clinical study of patients with osteogenesis imperfecta. OBJECTIVES To determine whether pulmonary compromise is more closely correlated with scoliosis, kyphosis, or chest wall deformity in the population with osteogenesis imperfecta, and to assess the impact of spinal deformity, chest wall deformity, and pulmonary function on quality of life. SUMMARY OF BACKGROUND DATA The incidence of scoliosis in osteogenesis imperfecta is between 39% and 80%. Up to 60% of patients with osteogenesis imperfecta have significant chest wall deformities. Pulmonary compromise is the leading cause of death in adults with osteogenesis imperfecta. METHODS Fifteen patients with osteogenesis imperfecta between the ages of 20 and 45 were evaluated with sitting or standing anteroposterior and lateral radiographs of the entire spine, pulmonary function testing, and a validated health self-assessment questionnaire (Short Form-36). Radiographs were evaluated for thoracic scoliosis, thoracic kyphosis, and chest wall deformity. Correlation analysis was performed. RESULTS Thoracic scoliosis was strongly correlated with decreased predicted vital capacity (r = -0.76). Significant diminution in vital capacity below 50% occurred at a curve magnitude of 60 degrees. Kyphosis and chest wall deformity were not predictive of decreased pulmonary function. Physical health (PCS) was closely correlated with predicted vital capacity (r = 0.65; P < 0.01) and with scoliosis (r = -0.52; P < 0.05). CONCLUSIONS Thoracic scoliosis of more than 60 degrees has severe adverse effects on pulmonary function in those with osteogenesis imperfecta. This finding may partly explain the increased pulmonary morbidity noted in adult patients with osteogenesis imperfecta and scoliosis compared with that in the general population.

Spinal deformity, pulmonary compromise, and quality of life in osteogenesis imperfecta.

STUDY DESIGN Prospective study. OBJECTIVES To prospectively evaluate sequential pulmonary function tests (PFTs) at a minimum 2-year follow-up after an open anterior spinal fusion (ASF) with instrumentation for thoracic AIS. SUMMARY OF BACKGROUND DATA Anterior spinal fusion with instrumentation is currently undergoing evaluation as an alternative to posterior spinal fusion (PSF) for thoracic adolescent idiopathic scoliosis (AIS). However, the effect of an open thoracotomy on pulmonary function in these patients is unknown. METHODS Fifty-one patients with thoracic AIS with an average age of 15+0 (range 11+2 to 20+5) had PFTs consisting of volume (FVC), flow (FEV-1), and total lung capacity (TLC). Parameters were obtained preoperatively, and at 3 months, 1 year, and a minimum 2-year follow-up. All patients had a single or double open thoracotomy with the diaphragm kept intact. Fusion levels ranged from T4 (most proximal) to L1 (most distal). The average preoperative thoracic coronal Cobb measurement was 53 degrees (range 38 degrees to 80 degrees ), and the average postoperative coronal measurement was 24 degrees (range 7 degrees to 49 degrees ). The average preoperative thoracic sagittal kyphosis (T5-T12) averaged 22 degrees (range 10 degrees to 58 degrees ), and the average postoperative sagittal kyphosis measured 29 degrees (range 7 degrees to 67 degrees ). RESULTS There was a significant decline (P< or =0.05) in PFT absolute values (L) of 19%-FVC, 15%-FEV-1, and 11%-TLC at 3 months postoperatively with subsequent improvement and no statistical difference between preoperative and 2-year postoperative values. When evaluating percent predicted values, there was a statistical decline (P< or =0.05) at 3 months postoperatively averaging 19% FVC, 14% FEV-1, and 12% TLC. These values returned to within 94% to 96% of baseline by the 2-year follow-up visit, but were still statistically less than the preoperative values (P</=0.05). CONCLUSIONS Pulmonary function following thoracotomy with ASF with instrumentation demonstrated a significant decline of 3-month postoperative PFT values, but returned to preoperative baseline absolute values (L) by the 2-year follow-up visit. The percent predicted values returned to within 95% of baseline 2 years postoperatively. Scoliosis surgeons should be aware of these findings when deciding upon the approach (anterior versus posterior) utilized for thoracic AIS.

Prospective pulmonary function evaluation following open thoracotomy for anterior spinal fusion in adolescent idiopathic scoliosis.

We studied the relationship of deterioration of cardiorespiratory function with respect to degree and localisation of apex of spinal curvature. The study comprised 33 patients (27 females and 6 males) aged 15 (11-21) years, surgically treated for an average scoliotic angle of 72 degrees (55-129 degrees, after Cobb) which was postoperatively reduced to 32.6 degrees (13-74 degrees). The static and dynamic cardiorespiratory function parameters were tested (pre-operatively and 24 months after surgery) by spirometry and plethysmography, arterial blood gas analysis, and the exercise tolerance test. In terms of the site and apex of the thoracic curve as determined by spine X-ray, patients were divided into two groups: upper thoracic scoliosis with the apex between T5 and T8 and lower thoracic scoliosis with the apex between T9 and T11. Only upper thoracic scoliosis with Cobb angle of more than 70 degrees correlated (r = -1) with restrictive ventilation disorder (vital capacity 68%) and latent hypoxaemia (uptake O2 ml/kg/min 63%) demonstrated during the exercise tolerance test (p > 0.05). The results of the test have demonstrated that surgically obtained 54% correction of the scoliotic curve improves pulmonary function (p < 0.05). However, the improvement does not match the degree of achieved scoliotic curve correction, what means that even in surgically treated high-angled thoracic scoliosis exists an increased risk of morbidity and mortality.

Cardiorespiratory function in surgically treated thoracic scoliosis with respect to degree and apex of scoliotic curve.

The aim of this study was to investigate the consequences of insulin-like growth factors (IGF) and IGF receptor dysfunction in lung carcinomas. A correlation between increased expression (at mRNA and protein levels) for IGF-1 and IGF-1R and decreased apoptosis were found in large-cell carcinomas and adenocarcinomas. In 40% of informative adenocarcinomas expressing the highest values of IGF-2 and Ki-67 proteins, M6P/IGF-2R gene had LOH at one allele and a mutation in another allele. All four squamous cell carcinoma samples expressed LOH/mutation in the M6P/IGF-2R gene. The αIR3 strongly diminished proliferation and increased apoptosis in cultures established from squamous cell carcinomas overexpressing IGF-2 and IGF-1R. Telomerase activity was assessed in four squamous cell carcinomas. Cell treatment with IGF-1 increased telomerase activity. The opposite was observed when the cells were treated with αIR3, which inhibits the activity of IGF-1 receptors. Our findings suggest that disruption of the IGF/IGF re...

The consequences of insulin-like growth factors/receptors dysfunction in lung cancer.

Nineteen patients with PHO with onset in childhood are presented. In 7 cases the syndrome was found in other family members too. In clinical, X-ray scintigraphic, arteriographic, and plethysmographic investigations, joint affection was found in 14 patients. Clubbing of the fingers and toes was seen in all the patients and a periosteal reaction was found in the long bones in 11 patients. Arteriography was carried out in 5 patients and showed hypervascularization and arteriovenous anastomoses in the clubbed fingers. The gas analysis of the arterial blood did not show any pathological changes. The histological finding showed poorly vascularized and oedematous periarticular tissue and ossification in the periosteal area, while in the synovial membrane, slight, nonspecific inflammatory changes were seen.

Primary hypertrophic osteoarthropathy (PHO) and changes in the joints. Clinical, X-ray, scintigraphic, arteriographic and histologic examination of 19 patients.

Two groups of patients, with an average age of 15 years, have been studied to establish the improvement in pulmonary function after surgical correction in relation to the amount of correction achieved. The first group of 33 patients were treated surgically; an average Cobb angle of 72° was reduced to 32.6°. The second group of 30 patients with an average Cobb angle of 33° were not operated on. Results of tests undertaken have shown that pulmonary function was improved by surgical correction, but the improvement does not match the degree of correction achieved. Statistical analysis of the two groups shows a difference in cardiopulmonary function to the advantage of those who were not operated on. This suggests that there is partial irreversibility of ventilation and perfusion in those who are treated surgically.

Pulmonary function in adolescents with idiopathic scoliosis.

The global use of guidelines for proper diagnosis and management of asthma was worldwide aimed toward obtaining effective control of asthma. Until now, the most often used guidelines in Croatia were the ones issued by the Global Initiative for Asthma (GINA). Their implementation significantly improved and uniformed the diagnosis and management of asthma at different levels of the national health system. The obtained level of knowledge has enabled the making of local guidelines which acknowledge economic, cultural and even traditional specificities of Croatia. It was supposed that Croatian medical professionals would more effectively use guidelines they actively supported to prepare and which were appropriated to local work environment and medicines available. Therefore, based on current scientific evidence, the Croatian Respiratory Society has prepared Croatian Guidelines for Diagnosis and Management of Asthma in Adults purposed for wide use among Croatian doctors and other health professionals.

Fadila Pavičić

Papers

Cardiorespiratory function in surgically treated thoracic scoliosis with respect to degree and apex of scoliotic curve.

The consequences of insulin-like growth factors/receptors dysfunction in lung cancer.

Primary hypertrophic osteoarthropathy (PHO) and changes in the joints. Clinical, X-ray, scintigraphic, arteriographic and histologic examination of 19 patients.

Pulmonary function in adolescents with idiopathic scoliosis.

Guidelines for diagnosis and management of asthma in adults of the Croatian Respiratory Society