Oxidative stress in patients with COPD and pulmonary hypertension

OBJECTIVE: Oxidative stress plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Oxidant/antioxidant imbalance has also been reported in various forms of pulmonary hypertension. The present study aimed to assess systemic oxidative stress, as reflected by serum malondialdehyde (MDA) concentrations and activities of antioxidant enzymes in erythrocytes [glutathione peroxidase (GPX), superoxide dismutase (SOD) and catalase (CAT)] in patients with and without pulmonary hypertension secondary to COPD. PATIENTS AND METHODS: Seventy-five patients (58 male) with COPD (mean age 65.1 +/- 1.2 years; mean smoking history 35.6 +/- 3.8 pack-years) were studied. Twenty-one healthy non-smokers served as a control group. Pulmonary function was evaluated with body plethysmography; mean and systolic pulmonary artery pressures (Ppa) were assessed with Doppler echocardiography. Serum concentrations of MDA and activities of GPX, SOD and CAT in washed red blood cells were measured using spectrophotometry. RESULTS: Pulmonary hypertension was present in 28 patients with COPD (systolic Ppa: 46.4 +/- 2.3 mmHg; mean Ppa: 26.0 +/- 1.9 mmHg) and absent in 47 (systolic Ppa: 22.9 +/- 0.8 mmHg; mean Ppa: 13.4 +/- 0.6 mmHg). Compared with the healthy control group, all the patients (with or without pulmonary hypertension) had higher serum MDA concentrations (1.5 +/- 0.1 versus 2.3 +/- 0.1 versus 2.3 +/- 0.1 nmol/mL, ANOVA, P < 0.001) and lower erythrocyte GPX activity (51.3 +/- 3.2 versus 42.2 +/- 2.0 versus 41.3 +/- 2.5 U/g Hb, P = 0.029), whereas SOD (1121.1 +/- 29.0 versus 1032.6 +/- 21.8 versus 1032.7 +/- 36.2 U/g Hb, P = 0.063) and CAT activities (4.9 +/- 0.2 versus 4.6 +/- 0.1 versus 4.7 +/- 0.2 U/g Hb; P= 0.454) were similar. No differences were observed in serum MDA concentrations or activities of GPX, SOD and CAT in erythrocytes between COPD patients with and without pulmonary hypertension. CONCLUSION: The study demonstrates the presence of oxidative/antioxidative imbalance in the systemic circulation in patients with COPD: compared with healthy subjects, COPD patients had higher serum MDA concentrations and lower GPX activity in erythrocytes. The magnitudes of the increase in MDA and reduction in GPX activity were similar in COPD patients with pulmonary hypertension and in those with normal pulmonary artery pressures.     

Behandlung des femoroazetabulären Impingements über den minimalinvasiven vorderen Zugang

Objective

Treatment of femoracetabular impingement to prevent or delay the development of secondary osteoarthritis of the hip. Improvement of the mechanical limitation of the range of motion of the hip joint. Pain-free movement of the hip.

Indications

Femoroacetabular impingement including a cam impingement, a pincer impingement, as well as mixtures of both types. Osteoarthritis of the hip joint grades 1–3 according to Kellgren induced by a femoroacetabular impingement.

Contraindications

Pincer impingement with the necessity of an osteotomy in acetabula malaligned in retroversion. Severe osteoarthritis grade 4 according to Kellgren. Hip infection.

Surgical Technique

Supine position of the patient. Longitudinal incision of 5–6 cm in line with the medial border of the anterior superior iliac spine at the level of the greater trochanter, two thirds cranially and one third distally of the tip of greater trochanter. Minimally invasive anterior approach in a modified technique of the Smith-Petersen approach with cutting of the fascia and preservation of the lateral femoral cutaneous nerve running between the two layers of the fascia. Blind preparation between the sartorius muscle and the tensor fasciae latae muscle. Preparation and T-shaped opening of the joint capsule in the direction of the capsule fibers and the anterior iliofemoral ligament. Removal of additional bone mostly in the ventral area of the femoral neck with angled and straight chisels. Using different positions of the leg helps to reach the more medial and lateral areas of the femoral neck. A trimming of the acetabulum with or without refixation of the labrum in the anterior and anterocranial acetabular rim is also possible. Documentation using fluoroscopy. Wound closure.

Postoperative Management

Prophylaxis of deep venous thrombosis. Early functional mobilization with unlimited range of motion of the hip joint. The amount of weight bearing is influenced by the amount of bone resection during trimming. In most cases, full weight bearing is possible. In cases of extensive bone resection (more than one fourth of the femoral neck diameter), gradual increase of weight bearing over 6 weeks.

Results

After a follow-up of 15.5 ± 6.8 months, 65 patients (20 female, 45 male; 70 hip joints) aged 40.2 ± 11.3 years showed an improvement of the Oxford Hip Score from 34.3 ± 9.8 points preoperatively to 16.3 ± 11.0 points and of the WOMAC (Western Ontario and McMaster Universities) Score from 60.8 ± 23.1 points to 84.0 ± 15.1 points at the latest follow-up examination. The impingement test was negative in all cases. In twelve cases, a temporary hypesthesia of the cranial innervation area of the lateral femoral cutaneous nerve was reported.     

FDG-PET/CT in large-vessel vasculitis: its diagnostic and follow-up role

Vasculitis is a disorder characterized by inflammation of blood vessels. Its clinical manifestations are diverse and depend on the size of the involved vessels and the organs affected by ischemia. In some cases the disease is manifested only with symptoms and signs of systemic inflammation (e.g. fever, night sweats, fatigue). Results of laboratory tests usually indicate only the inflammatory process. It is known that radiolabeled glucose analogue 18F-fluoro-deoxyglucose ([18F] FDG) used in positron emission tomography (PET) accumulates in both malignant and inflammatory tissue (Zhuang et al. in Radiol Clin North Am 43:121–134, 2005). We report a case of a patient with FDG-PET/CT findings of large-vessel vasculitis with follow-up results that convinced us to change the treatment.     

Epidermal growth factor receptor (EGFR) high gene copy number and activating mutations in lung adenocarcinomas are not consistently accompanied by positivity for EGFR protein by standard immunohistochemistry

The purpose of this study was to investigate whether detectable protein biomarker overexpression is a prerequisite for the presence of increased gene copy number or activating mutations and responsiveness to the epidermal growth factor receptor (EGFR) inhibitors gefitinib and erlotinib in patients with lung adenocarcinomas. EGFR status was prospectively analyzed in tumor biopsy samples by three methods: protein expression (n = 117) by standardized immunohistochemistry (IHC), gene copy number (n = 97) by fluorescent in situ hybridization (FISH), and mutation analysis by sequencing (n = 126). Fifty-nine percent of the samples were positive by IHC, 40% were positive by FISH, and 13.5% contained activating kinase domain mutations. Thirty-four percent of the FISH-positive and 27% of the mutant samples were also IHC-negative. All EGFR mutant patients had major clinical responses (five complete response and five partial response) to gefitinib or erlotinib treatment, although three of these tumors were IHC-negative and four were FISH-negative. In a retrospective analysis of samples from nine patients with excellent therapeutic responses (three complete response, five partial response, one stable disease) to erlotinib or gefitinib, mutations were identified in eight cases, but IHC was negative in four of these tumors. These results indicate that molecular diagnostic methods appear to be most important for the identification of lung adenocarcinoma patients who may benefit from EGFR inhibitor treatments.     

Patients with acute coronary syndromes have low tissue factor activity and microparticle count,but normal concentration of tissue factor antigen in platelet free plasma – a pilot study

Objectives: Tissue factor (TF) is a main initiator of coagulation cascade. Its determination in conditions of acute coronary syndrome is logistically difficult. Hence, in our study, the activity and the concentration of TF and the count of microparticles in the platelet free plasma (PFP) were determined. Methods: Blood was drawn from both coronary sinus and femoral vein circulation in a cohort of 40 patients. TF activity was measured by activation of factor X in the presence of factor VIIa, whereas microparticles were detected using flow cytometry. TF antigen concentrations were determined using the ELISA test. Results: TF activity in the stable angina subgroup was not significantly different from the control group (18.12 ± 3.35 mOD/min vs. 17.72 ± 4.05 mOD/min, respectively), but it was significantly lower in the unstable angina (7.62 ± 4.19 mOD/min) and myocardial infarction (MI) (3.56 ± 3.85 mOD/min) subgroups (P < 0.05). Results from the coronary sinus and femoral vein circulations were not significantly different. The count of microparticles decreased according to the severity of the acute coronary syndrome: control group, 520 ± 172; stable angina subgroup, 532 ± 167; unstable angina subgroup, 392 ± 142; and MI subgroup, 165 ± 30 (P < 0.05). There were no significant differences in concentrations of TF antigen in four subgroups. Conclusions: These results suggest that the procoagulant TF‐bearing microparticles could be recruited from PFP by interaction with platelets and blood cells in the conditions of acute coronary syndrome.     

Bacteremias caused by Escherichia coli in cancer patients - analysis of 65 episodes.

OBJECTIVES: The aims of this study were to evaluate risk factors, clinical presentation, outcome and antimicrobial susceptibility in patients with Escherichia coli bacteremia occurring over seven years in a single cancer hospital. METHODS: Sixty five episodes of bacteremia from E. coli appearing over seven years from 12,301 admissions in a single cancer institution were retrospectively analyzed. RESULTS: The proportion of bacteremia caused by E. coli among Gram-negative bacteremia was 20.8% (the second most common organism after Pseudomonas aeruginosa), and infection-associated mortality was 17%. The incidence in 1989-1995 varied from 14.3 to 24.7%. The most common risk factors were: solid tumors as the underlying disease (70.7%); central venous catheter insertion (32.3%); prior surgery (46.2%), and prior chemotherapy within 48 h (44.4%). Neutropenia and urinary catheters did not place patients at high risk in any of the subgroups. When we compared the two subgroups of 61 cases of bacteremia - monomicrobial and polymicrobial (when E. coli was isolated from blood culture with another microorganism) - we found that acute leukemia and breakthrough (recurrence while receiving antibiotics) bacteremia were more frequently associated with polymicrobial E. coli bacteremia. There was also a difference in infection-associated mortality: monomicrobial bacteremia due to E. coli only had a significantly lower mortality in comparison with polymicrobial E. coli bacteremia (8.9 vs 35.0%, respectively; P<0.03). CONCLUSION: The susceptibility of 115 E. coli strains isolated from 65 episodes of bacteremia was stable. Only two episodes caused by quinolone-resistant strains occurred, both in 1995, after six years of using ofloxacin for prophylaxis in neutropenic patients in our hospital. We found that 85.2-91.3% of all strains were susceptible to aminoglycosides, 97.8% to quinolones, and 90-100% to third generation cephalosporins and imipenems. The patients most commonly infected had solid tumors and the mortality was only 17%.