Pulmonary hypertension secondary to chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is the most common cause of secondary pulmonary hypertension (PH). PH secondary to COPD is associated with a worse prognosis of the disease, a low quality of life, as well as with a higher exacerbation frequency, and consequently with an increase in the healthcare cost of COPD patients. Prevalence of PH in COPD patients is currently unknown. The most important mechanisms leading to PH are hypoxic vasoconstriction, pulmonary hyperinflation and endothelial dysfunction. PH should be suspected in COPD patients in the presence of severe dyspnoea, disproportionate from the decline in lung function, or of severe hypoxemia. Exercise induced PH is an independent predictor of the development of resting PH in patients with COPD. Echocardiography is the first screening method for PH in patients with COPD and it should be widely used, as it can also appreciate the cardiac consequences of PH, especially on the right ventricle. Given the high negative predictive value of the echocardiographic estimation of systolic pulmonary arterial pressure (sPAP) in the diagnosis of PH, the absence of a high sPAP excludes important PH and further unnecessary invasive evaluation. Right cardiac catheterization remains the "gold standard" method in assessing PH, but it is less accessible and cannot be used in routine evaluation of patients with COPD. PH secondary to COPD is usually mild, but a small proportion of patients have severe PH, with specific characteristics, worse prognosis and a specific therapeutic approach.

The metabolic and inflammatory profile in obese patients with chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease and obesity are major causes of morbidity and mortality worldwide and, according to current data, the global burden of these conditions will increase further. Obesity plays a major role in the development of the metabolic syndrome and has been identified as an important risk factor for chronic diseases such as type 2 diabetes mellitus and cardiovascular disease. Adiposity is associated with insulin resistance even over relatively normal ranges of body fatness. There is strong evidence that altered adipose tissue function plays a crucial role in the pathogenesis of obesity-related insulin resistance and type 2 diabetes, as has recently been reviewed. Obesity is linked to respiratory diseases such as obstructive sleep apnea syndrome and obesity hypoventilation syndrome and accumulating evidence suggests an association between obesity and asthma. A potential link between obesity and COPD is also increasingly recognized although little data is known about the mechanisms underlying this association. The inflammatory and metabolic profile differs between obese with COPD and normo or underweight with COPD in part due to dysfunction of adipose tissue.

Are systemic inflammatory profiles different in patients with COPD and metabolic syndrome as compared to those with COPD alone?

BACKGROUND: Metabolic Syndrome (MS) is frequent in patients with COPD, almost 50% of patients with COPD had one or more components of metabolic syndrome (MS). Moreover, it was demonstrated that BMI might be one of the determinants of COPD phenotype. Chronic comorbid diseases affect health outcomes in COPD, in fact, patients with COPD mainly die of non-respiratory disorders such as cardiovascular disease. Inflammation plays a key role in COPD and MS but we do not know the real inflammatory profile of these patients. A better understanding of the origin and consequences of systemic and local inflammation, and of potential therapies, will most likely lead to better care of patients with COPD. METHODS: We compared 64 consecutive, consenting smoker patients with COPD and MS (mean age: 62.7 +/- 0.7 years) with this serum inflammatory profile (hsCRP: 1.9 +/- 0.01 mg/dL, TNF-alpha: 6,4 +/- 0.1 pg/mL, adiponectin: 4.7 +/- 0.01 mg/L) versus 69 COPD smoker patients matched for age (mean age 61.4 +/- 0.4 years) with following serum inflammatory cytokine (CRP: 0.9 +/- 0.01 mg/dL, TNF-alpha: 3.9 pg/mL +/- 0.01, adiponectin: 9.3 +/- 0.01 mg/L). COPD and MS was diagnosed according to the GOLD criteria respectively IFD 2005 criteria. Data were expressed as mean +/- SE (standard error). Comparisons of parameters among the two groups were made by Student unpaired t test. The level of statistical significance was set as p < 0.05. RESULTS: Serum TNF-alpha and high-sensitivity CRP levels in patients with COPD and MS were significantly higher (p < 0.05) than those of COPD alone. Plasma adiponectin levels in patients with COPD were significantly higher (p < 0.05) than in subjects with COPD and MS. CONCLUSIONS: Patients with COPD and MS have a more exacerbated systemic inflammatory profile and a significantly reduced specific adipose response represented by adiponectin than patients with COPD alone. These results help us to better understand the inflammatory pattern in patients with COPD with metabolic disorders and permit us to sustain the regulatory role of adiponectin in metabolism balance. It is possible that this association between COPD and MS with a specific inflammatory pattern (high serum levels of CRP and TNF-a but with low plasma levels of adiponectin) to explain the high rate of death adjudicated as due to cardiovascular causes.

CT angiography in complex upper extremity reconstruction.

Computed tomography angiography is a new technique that provides high-resolution, three-dimensional vascular imaging as well as excellent bone and soft tissue spatial relationships. The purpose of this study was to examine the use of computed tomography angiography in planning upper extremity reconstruction. Seventeen computed tomography angiograms were obtained in 14 patients over a 20-month period. All studies were obtained on an outpatient basis with contrast administered through a peripheral vein. All the studies demonstrated the pertinent anatomy and the intraoperative findings were as demonstrated in all cases. Information from two studies significantly altered pre-operative planning. The average charge for computed tomography angiography was 1,140 dollars, compared to 3,900 dollars for traditional angiography.

Efficacy and safety of inhaled budesonide delivered once or twice daily via HFA-134a in mild to moderate persistent asthma in adult patients. Comparison with budesonide CFC.

This study was undertaken to investigate whether budesonide 4001 microg twice daily (Chiesi Farmaceutici S.p.A.) given with the HFA-134a propellant is equivalent in efficacy and safety to the same dose regimen delivered with the marketed CFC product in adult asthmatics with mild to moderate persistent asthma; the effects of budesonide HFA 800 microg once daily were also studied. After a 2-week run-in, a total number of 98, 103 and 97 patients were assigned to the 12-week treatment with budesonide given with HFA or CFC twice daily (morning and evening), or HFA once daily (morning), respectively. The main outcome variable morning PEFR, as well as evening PEFR and clinical symptoms (day-time and night-time asthma attacks, number of asthma-induced night-time awakenings and overall symptoms' scores) were measured daily by patients. Other standard pulmonary function testing were measured at clinic visits. A blood sample for morning serum dosing (8.00-10.00 AM) was taken at baseline and at endpoint. Adverse events and vital signs were also recorded. Significant improvements at endpoint in morning and evening PEFR, as well as in clinic PEFR and MEF50, were observed in both the twice daily groups only. An exact proof of equivalence between HFA and CFC given twice daily was demonstrated for the primary parameters, morning PEFR (equivalence pre-defined limits were +/- 40.27 l/min, difference between means = 4.0 l/min and 95% CI -6.9-14.9) and secondary parameters as evening PEFR: (limits +/- 40.19 l/min, difference between means = 2.1 l/min and 95% Confidence interval (CI) -9.4-13.5) and FEV1 (limits +/- 0.27 l, difference between means = 0.0 l and 95% CI -0.11-0.10). Less evident (but within limits) proofs of equivalence were shown in the comparisons with the once daily group. No substantial differences between the three groups were observed for the other efficacy variables, including symptoms and use of rescue salbutamol, which significantly improved over the run-in values in all groups. Minimal and non-significant decreases over pre-treatment values were observed in the three groups for morning serum cortisol levels: the analysis of individual data has shown a better outcome in the HFA twice daily regimen, compared with the other two groups. Again, a similar amount of patients in both the twice daily groups reported drug-related adverse events, which were more frequent in the once daily HFA group. Therefore, the results of this study have shown that inhaled budesonide given with new HFA-134a propellant can replace microgram-equivalent doses of the corresponding marketed CFC product when given twice daily. An overall maintainment and an unchanged risk-benefit ratio has emerged for budesonide HFA given once daily, which was however slightly inferior compared with the standard twice daily regimens.

Gene expression of transforming growth factor beta isoforms in interposition nerve grafting.

Scar production and neuroma formation at nerve graft coaptation sites may limit axonal regeneration and impair functional outcome. Transforming growth factor beta (TGF-beta) is a family of growth factors that is involved in scar formation, wound healing, and nerve regeneration. Fifteen adult Sprague-Dawley rats underwent autogenous nerve grafting. The nerve grafts were analyzed by in situ hybridization to determine the temporal and spatial expression of TGF-beta1 and TGF-beta3 messenger RNA (mRNA). The grafted nerves showed increased expression of TGF-beta1 and TGF-beta3 mRNA in the nerve and the surrounding connective tissue during the first postoperative week. These data suggest that modulation of TGF-beta levels in the first postoperative week may be effective in helping to control scar formation and improve nerve regeneration.

[Monocrotaline induce pulmonary hypertension in animal models]. / Monocrotalina, inductor al hipertensiunii pulmonare pe modele experimentale.

The pulmonary hypertension is a serious disease, difficult to treat, and its mechanisms remain however to be elucidated. It is known that administration of small doses of MCT or its active metabolite, monocrotaline pyrrole (MCTP); to rats causes delayed and progressive lung injury characterized by pulmonary vascular remodeling which induces pulmonary hypertension. The purpose of this article is to get used to vascular, cellular and molecular changes in pulmonary hypertension, in order to create a personal experimental animal model. This experimental model will try to find new ways of therapeutical strategies in human pulmonary hypertension.

A randomization test-based method for risk assessment in neurotoxicology.

A current trend in risk assessment for systemic toxicity (noncancer) endpoints is to utilize the observable range of the dose-effect curve in order to estimate the likelihood of obtaining effects at lower concentrations. Methods to accomplish this endeavor are typically based on variability in either the effects of fixed doses (benchmark approaches), or on variability in the doses producing a fixed effect (probabilistic or tolerance-distribution approaches). The latter method may be particularly desirable because it can be used to determine variability in the effect of an agent in a population, which is an important goal of risk assessment. This method of analysis, however, has typically been accomplished using dose-effect data from individual subjects, which can be impractical in toxicology. A new method is therefore presented that can use traditional groups-design data to generate a set of dose-effect functions. Population tolerances for a specific effect can then be estimated from these model dose-effect functions. It is based on the randomization test, which assesses the generality of a data set by comparing it to a data set constructed from randomized combinations of single point estimates. The present article describes an iterative line-fitting program that generates such a data set and then uses it to provide risk assessments for two pesticides, triadimefon and carbaryl. The effects of these pesticides were studied on the locomotor activity of laboratory rats, a common neurobehavioral end point. Triadimefon produced dose-dependent increases in activity, while carbaryl produced dose-dependent decreases in activity. Risk figures derived from the empirical distribution of individual dose-effect functions were compared to those from the iterative line-fitting program. The results indicate that the method generates comparable risk figures, although potential limitations are also described.

Community acquired methicillin-resistant Staphylococcus aureus hand infections: case reports and clinical implications.

We report a series of 4 cases of community acquired methicillin-resistant Staphylococcus aureus hand infections in patients without risk factors. Methicillin-resistant S aureus infections commonly involve the skin and soft tissue; therefore, hand infections may become more common as the prevalence of this pathogen increases. Hand surgeons must be aware of this emerging pathogen and obtain appropriate tissue cultures to diagnose and effectively treat this infection.