Preoperative pulmonary rehabilitation in patients undergoing lung resection for non-small cell lung cancer.

BACKGROUND: The impact of short-term preoperative pulmonary rehabilitation on exercise capacity of patients with chronic obstructive pulmonary disease undergoing lobectomy for non-small cell lung cancer is evaluated. METHODS: A prospective observational study was designed. Inclusion criteria consisted of an indication to lung resection because of a clinical stage I or II non-small cell lung cancer and a chronic obstructive disease on preoperative pulmonary function test. In such conditions, maximal oxygen consumption by a cardio-pulmonary exercise test was evaluated; when this resulted as being < or =15 ml/kg/min a pulmonary rehabilitation programme lasting 4 weeks was considered. Twelve patients fulfilled inclusion criteria, completed the preoperative rehabilitation programme and underwent a new functional evaluation prior to surgery. The postoperative record of these patients was collected. RESULTS: On completion of pulmonary rehabilitation, the resting pulmonary function test and diffuse lung capacity of patients was unchanged, whereas the exercise performance was found to have significantly improved; the mean increase in maximal oxygen consumption proved to be at 2.8 ml/kg/min (p<0.01). Eleven patients underwent lobectomy; no postoperative mortality was noted and mean hospital stay was 17 days. Postoperative pulmonary complication was recorded in 8 patients. CONCLUSIONS: Short-term preoperative pulmonary rehabilitation could improve the exercise capacity of patients with chronic obstructive pulmonary disease who are candidates for lung resection for non-small cell lung cancer.     

Disability-Adjusted Life Years Averted Versus Quality-Adjusted Life Years Gained: A Model Analysis for Breast Cancer Screening

ObjectivesTo quantify the impact of mammography-based screening on the quality of life, disability-adjusted life years (DALYs) averted or quality-adjusted life years (QALYs) gained can be used. We aimed to assess whether the use of DALYs averted or QALYs gained will lead to different cost-effective screening strategies.MethodsUsing the microsimulation model MISCAN, we simulated different breast cancer screening strategies varying in starting age (starting at 45, 47, and 50 years), stopping age (stopping at 69, 72, and 74 years), and frequency (annual [A], biennial [B], combination of both [A + B], and triennial [T]). In total, we defined 24 different breast cancer screening strategies, including no screening as a reference strategy. We calculated incremental cost-effectiveness ratios (ICERs) and compared which strategies were on the efficiency frontiers for DALYs and QALYs.ResultsBreast cancer screening averted between 46.00 and 105.58 DALYs and gained between 28.69 and 64.50 QALYs per 1000 women. For DALYs there were 5 strategies on the efficiency frontier (T50-69, T50-74, T45-74, B45-74, and A45-74). The same strategies plus one (B45-72) were on the efficiency frontier for QALYs.ConclusionsUsing DALYs averted instead of QALYs gained to assess the effects on quality of life from breast cancer screening in the Dutch population yields differences in ICERs, but almost the same strategies were on the efficiency frontiers. Whether the choice in outcome measure leads to a difference in optimal policy depends on the cost-effectiveness threshold.     

Bilateral cystoid macular edema following successful treatment of AIDS-associated CMV retinitis

Background: Cystoid macular edema (CME) in AIDS patients with inactive cytomegalovirus (CMV) retinitis is an uncommon but potentially sight-threatening complication. The pathogenesis of CME in these patients is unclear. This study tries to identify possible risk factors by analyzing the charts of five patients. Methods: Ten eyes of 5 patients that finally developed CME were followed for an average of 18 months. The initial retinal lesions, their response to antiviral treatment, the development of CME, and the patients' immune status were prospectively monitored. Results: CMV retinitis was diagnosed at a median CD4+ count of 3 cells/mm³ (range 0–11). All eyes responded to the initial systemic anti-viral treatment. At the onset of CME, CMV retinitis was controlled by antiviral maintenance therapy in all patients [ganciclovir (n = 2), cidofovir (n = 2), foscarnet (n = 1)]. The median time between diagnosis of CMV retinitis and onset of CME was 11.5 months (range 5–24). Development of CME was associated with significant visual loss: acuity ranged from 0.05 to 0.7 when CME was first noticed, compared to 0.8–1.25 at diagnosis of CMV retinitis. Duration of inflammation, size or zone of retinal necrosis did not favor the development of CME, neither did the antiviral therapy. A weak correlation of CME development and immune status (expressed as increase of CD4+ cells) was found. Due to systemic corticosteroids CME resolved. Conclusions: CME is a new visual threat to AIDS-patients with CMV retinitis whose immune status improved under the latest combined antiretroviral therapy. Therapy with oral corticosteroids may positively influence this condition.      

Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: REGULATION OF RENAL TUBULAR SODIUM TRANSPORT BY ANGIOTENSIN II AND ATRIAL NATRIURETIC FACTOR

• 1 The effects of angiotensin II (AngII) on water and electrolyte transport are biphasic and dose-dependent, such that low concentrations (10^?12 to 10^?9 mol/L) stimulate reabsorption and high concentrations (10^?7 to 10^?6 mol/L) inhibit reabsorption. Similar dose-response relationships have been obtained for luminal and peritubular addition of AngII.
• 2 The cellular responses to AngII are mediated via AT₁ receptors coupled via G-regulatory proteins to several possible signal transduction pathways. These include the inhibition of adenylyl cyclase, activation of phospholipases A₂, C or D and Ca²⁺ release in response to inositol-1,4,5,-triphosphate or following Ca²⁺ channel opening induced by the arachidonic acid metabolite 5,6,-epoxy-eicosatrienoic acid. In the brush border membrane, transduction of the AngII signal involves phospholipase A₂, but does not require second messengers.
• 3 Angiotensin II affects transepithelial sodium transport by modulation of Na⁺/H⁺ exchange at the luminal membrane and Na⁺/HCO₃ cotransport, Na⁺/K⁺-ATPase activity and K⁺ conductance at the basolateral membrane.
• 4 Atrial natriuretic factor (ANF) does not appear to affect proximal tubular sodium transport directly, but acts via specific receptors on the basolateral and brush border membranes to raise intracellular cGMP levels and inhibit AngII-stimulated transport.
• 5 It is concluded that there is a receptor-mediated action of ANF on proximal tubule reabsorption acting via elevation of cGMP to inhibit AngII-stimulated sodium transport. This effect is exerted by peptides delivered at both luminal and peritubular sides of the epithelium and provides a basis for the modulation by ANF of proximal glomerulotubular balance. The evidence reviewed supports the concept that in the proximal tubule, AngII and ANF act antagonistically in their roles as regulators of extracellular fluid volume.

     

Attitude towards pre-implantation genetic diagnosis for hereditary cancer

The use of pre-implantation genetic diagnosis (PGD) for hereditary cancer is subject to on-going debate, particularly among professionals. This study evaluates the attitude towards PGD and attitude-associated characteristics of those concerned: family members with a hereditary cancer predisposition. Forty-eight Von Hippel-Lindau and 18 Li–Fraumeni Syndrome families were identified via the 9 family cancer clinics in the Netherlands. In total, 216 high risk family members and partners were approached, of whom 179 (83%) completed a self-report questionnaire. Of the high risk family members, 35% expressed a positive attitude towards PGD. Those with a current desire to have children were significantly more likely to have a positive attitude: 48% would consider the use of PGD. No other sociodemographic, medical or psychosocial variables were associated significantly with a positive attitude. The most frequently reported advantage of PGD is the avoidance of a possible pregnancy termination. Uncertainty about late effects was the most frequently reported disadvantage. These results indicate that approximately half of those contemplating a future pregnancy would consider the use of PGD. The actual uptake, however, is expected to be lower. There is no indication that psychosocial factors affect interest in PGD.     

Morphine‐6‐glucuronide (M6G) for postoperative pain relief

Morphine‐6‐glucuronide (M6G) is morphine's active metabolite acting at the μ‐opioid receptor. Recent experimental human studies and 5 of 6 randomized clinical trials indicate that M6G causes adequate and long lasting pain relief comparable to morphine. There are various observations that M6G is associated with a reduction in the severity of side effects normally associated with opioid use, such as reduced postoperative nausea and vomiting (PONV) and reduced respiratory depression. The present drug profile provides a review of the pharmacological properties of M6G, the clinical evidence relating to its efficacy and safety, and discusses its future role in the treatment of postoperative pain.     

Recombinant human monoclonal autoantibodies specific for citrulline-containing peptides from phage display libraries derived from patients with rheumatoid arthritis

OBJECTIVE: To isolate and characterize monoclonal autoantibodies (Mab) directed to citrullinated antigens from patients with rheumatoid arthritis (RA). METHODS: Using lymphocytes from bone marrow or peripheral blood from RA patients, we constructed antibody fragment libraries representing the antibody repertoire of these individuals. Antibody fragments recognizing a citrulline-containing peptide were selected from these patient libraries. Individual antibody clones were analyzed for germline gene usage and reactivity toward citrullinated (auto)-antigens. RESULTS: Sequence analysis of the cDNA encoding the 21 distinct antibody fragments that were obtained revealed a restricted germline gene usage. Individual antibody clones were positive in both antiperinuclear factor (APF) and antikeratin antibody (AKA) tests, stained citrullinated filaggrin and fibrinogen on Western blots, and reacted with subsets of citrulline-containing peptides in ELISA, but not with noncitrullinated peptides. CONCLUSION: Our report describes the first recombinant human Mab fragments reactive with citrulline-containing peptides. The restricted germline gene usage of these antibodies, and the fact that the VH alleles used are not present in all individuals, may indicate the existence of a genetic predisposition for the development of anticitrulline antibodies in individuals with these germline alleles. The selected antibody clones may facilitate studies on the role of these autoantibodies and their target antigens in the development of RA.