Open <Emphasis Type="Italic">vs.</Emphasis> Laparoscopic Surgery for Rectal Prolapse

PURPOSE: This study was undertaken to evaluate the efficacy and safety of laparoscopic repair for rectal prolapse. METHODS: A case-control study was undertaken. The case group consisted of a consecutive series of patients who underwent laparoscopic repair for rectal prolapse between February 1993 and June 2000. The control group underwent open prolapse repair between October 1987 and January 2000. RESULTS: There were 53 patients in each group. The groups were matched according to operation type, gender, and age. Median operative time was longer in the case group than in the control group (resection rectopexy 210 vs. 117 minutes, rectopexy 127.5 vs. 72 minutes, respectively). Median postoperative hospital stay was shorter in the case group than in the control group (resection rectopexy 5 vs. 7 days, rectopexy 4.5 vs. 7 days, respectively). Median intraoperative bleeding was minor in the case group (resection rectopexy 35 vs. 300 ml, rectopexy 15 vs. 100 ml, respectively). Mortality (0 vs. 4 percent), complications (23 vs. 30 percent), late complications (4 vs. 13 percent), and the rate of recurrent prolapse (6 vs. 13 percent) did not differ significantly between the groups. CONCLUSIONS: Laparoscopic repair for rectal prolapse is technically feasible and can be performed with mortality and morbidity rates comparable to those of the conventional technique. The main advantages of the laparoscopic approach appear to be a shorter hospital stay and lessened intraoperative blood loss. Recurrence rate is not increased in the short term.     

IL-7 concentration is increased in nonagenarians but is not associated with markers of T cell immunosenescence

Interleukin-7 is a homeostatic cytokine that contributes to the maintenance of the T cell pool. It also has proinflammatory effects and is involved in the pathogenesis of autoimmune diseases. Due to its homeostatic effects, IL-7 has been proposed as a potential rejuvenation factor for the elderly immune system. We analyzed the correlation of plasma IL-7 concentrations and the proportions of different T cell populations in nonagenarians (n=163) participating in the Vitality 90+ study. Young individuals (n=35, aged 19-30years) were used as controls. The numbers of CD3+, CD14+, CD4+ and CD8+ cells and the expression of the CD28 costimulatory molecule on CD4+ and CD8+ lymphocyte subsets were analyzed using flow cytometry. The plasma IL-7 levels were significantly higher in the nonagenarians compared to the controls (7.86 vs. 5.74pg/ml, p=0.004). In the nonagenarians, plasma IL-7 levels correlated inversely with the proportion of CD3+ T cells and directly with the proportion of CD14+ monocytes and plasma C-reactive protein. No correlation was observed between plasma IL-7 levels and the proportions of CD4+CD28- or CD8+CD28- subsets. These results suggest that the IL-7 levels in nonagenarians do not have an inhibitory effect on the development of immunosenescence; rather they are associated with increased inflammation.     

Low Parathyroid Hormone Levels in Bedridden Geriatric Patients with Vitamin D Deficiency

OBJECTIVES: To identify the clinical conditions associated with low parathyroid hormone (PTH) in patients with vitamin D deficiency and to evaluate the stability of the blunted PTH response to vitamin D deficiency over 6 months.
DESIGN: Secondary analysis of a randomized double-blind controlled vitamin D supplementation trial.
SETTING: Four long-term care hospitals in Helsinki, Finland.
PARTICIPANTS: Two hundred eighteen chronically bedridden patients.
MEASUREMENTS: Plasma 25-hydroxyvitamin D (25-OHD), intact PTH, amino-terminal propeptide of type I procollagen (PINP), carboxy-terminal telopeptide of type I collagen (ICTP), activities of daily living (ADLs), and body mass index (BMI) were measured at baseline and at 6 months. Patient records were reviewed for demographic data.
RESULTS: PTH was within reference values (8–73 ng/L) despite low 25-OHD level (<50 nmol/L) in 74.8% (n=163) of patients (mean age 84.5±7.5). Patients in the lowest PTH quartile (<38 ng/L) were characterized by a history of hip fractures (OR=2.9, P =0.01), low BMI (OR=0.9, P =.02), and high ICTP (OR=1.1, P =.03). PTH remained within reference values even after 6 months in 76.2% of the patients with persistent vitamin D deficiency in the placebo group.
CONCLUSION: The absence of secondary hyperparathyroidism seems to be common and persistent in frail chronically bedridden patients with vitamin D deficiency. Attenuated parathyroid function appears to be associated with immobilization that causes accelerated bone resorption. Further studies addressing the possible adverse effects of low PTH are warranted.     

Responses of parathyroid hormone to vitamin D supplementation: a systematic review of clinical trials

The beneficial bone effects of vitamin D supplementation have been attributed to suppression of secondary hyperparathyroidism by 25-hydroxyvitamin D (25-OHD) levels at least 50nmol/l. In this systematic review, we have analyzed the results of 52 clinical trials, including 72 intervention groups and 6290 patients, on vitamin D supplementation in order to evaluate the experimental evidence and the effects of age and chronic immobility on responses of parathyroid hormone (PTH). The papers for this systematic review were selected through a search in PubMed and through a review of the reference lists of articles. Negative logarithmic (R(2)=0.318, p<0.001) and linear (R(2)=0.294, p<0.001) correlations were found between 25-OHD and PTH levels, when all pre- and post-trial values were scattered. Negative linear (R(2)=0.385, p<0.001) and logarithmic (R(2)=0.406, p<0.001) correlations were also found between the changes in 25-OHD and PTH levels. Age correlated negatively with changes in PTH (r=-0.476, p<0.001). The vitamin D supplementation of the chronically immobile patients resulted in a smaller decrease in PTH levels (-8.4 vs. -17.4%, p<0.001) despite a larger increase in 25-OHD levels (187.2% vs. 109.8%, p<0.001). According to the multiple regression analysis the changes in PTH were independently predicted by pre-trial PTH, changes in 25-OHD, age and chronic immobility, explaining 53.2% (R(2)=0.532) of the variation. This meta-analysis shows that responses of PTH to vitamin D supplementation are not only determined by the baseline PTH levels and changes in vitamin D status, but also by age and mobility of the patients. Our results also suggest that PTH decreases quite linearly during vitamin D supplementation at any given 25-OHD level. Longitudinal vitamin D supplementation studies on populations with wide range of mobility and age are needed to further elucidate their confounding effects. In determining the sufficient doses of vitamin D supplementation and adequate 25-OHD levels, these confounding effects and the inter-individual variation in responses of PTH to vitamin D supplementation should be taken into account.     

Bursts of activity in collective cell migration

Dense monolayers of living cells display intriguing relaxation dynamics, reminiscent of soft and glassy materials close to the jamming transition, and migrate collectively when space is available, as in wound healing or in cancer invasion. Here we show that collective cell migration occurs in bursts that are similar to those recorded in the propagation of cracks, fluid fronts in porous media, and ferromagnetic domain walls. In analogy with these systems, the distribution of activity bursts displays scaling laws that are universal in different cell types and for cells moving on different substrates. The main features of the invasion dynamics are quantitatively captured by a model of interacting active particles moving in a disordered landscape. Our results illustrate that collective motion of living cells is analogous to the corresponding dynamics in driven, but inanimate, systems.Collective cell movement depends on intracellular biological mechanisms as well as environmental cues due to the extracellular matrix (1–5), mainly composed of collagen which is organized in hierarchical structures, such as fibrils and fibers. The mechanical properties of collagen fibril networks are essential to offer little resistance and high sensitivity to small deformations, allowing easy local remodeling and strong strain stiffening needed to ensure cell and tissue integrity (6). Wound healing is a typical biological assay to study collective migration of cells under controlled conditions in vitro and is a prototypical experimental method to study active matter (7–10). Experiments performed on soluble collagen (11) or other gels (12), micropatterned (13, 14) and deformable substrates (1) show that cell migration is guided by the substrate structure and stiffness (5, 15, 16).It has been argued that collective migration properties arise from stresses transmitted between neighboring cells (1) giving rise to long-ranged stress waves in the monolayer (17, 18). Hence the dynamics of an invading cell sheet is ruled by a combination of long-range internal stresses and interactions with the substrate, suggesting an analogy with driven elastic systems moving in a disordered medium such as cracks lines (19, 20), imbibition fronts (21), or ferromagnetic domain walls (22). The scaling laws in these systems are usually associated with a depinning critical point that has been widely studied by simple models for interface dynamics. Thanks to a combination of numerical simulations (23, 24) and renormalization group theory (23, 25–27), we now have a detailed picture of the nonequilibrium phase transitions and universality classes in these systems. Here we substantiate the analogy between collective cell migration and depinning by revealing and characterizing widely distributed bursts of activity in the collective migration of different types of cells (human cancer cells and epithelial cells, mouse endothelial cells) over different substrates (plastic, soluble, and fibrillar collagen) and experimental conditions [vascular endothelial (VE)-cadherin knockdown] and compare the experiments with simulations of a computational model of active particles (10). We find that in all these cases the statistical properties of the bursts follow universal scaling laws that are quantitatively similar to those observed in driven disordered systems (28).     

Patients with asthma or chronic obstructive pulmonary disease (COPD) can generate sufficient inspiratory flows via Easyhaler® dry powder inhaler: a pooled analysis of two randomized controlled trials

BackgroundTo evaluate whether patients of varying ages and lung function with asthma or those with chronic obstructive pulmonary disease (COPD) can achieve sufficient inspiratory flows for effective use of the fixed-dose combination of salmeterol-fluticasone propionate and budesonide-formoterol dispensed with the Easyhaler^® (EH) device-metered, multi-dose dry powder inhaler (DPI).MethodsA pooled analysis of two randomized, multicenter, crossover, open-label studies ({"type":"clinical-trial","attrs":{"text":"NCT01424137","term_id":"NCT01424137"}}NCT01424137; NCT009849061) was conducted to characterize inspiratory flow parameters across the EH, Seretide Diskus (DI) and Symbicort Turbuhaler (TH) inhalers in patients with asthma and/or COPD of varying severity. The primary endpoint was peak inspiratory flow (PIF) rate through the EH.ResultsThe intent-to-treat population comprised 397 patients; 383 patients were included in the per-protocol (PP) population. The mean PIF (standard deviation) values through the EH in patients <18 and ≥18 years of age with asthma and in those with COPD, were similar: 61.4 (11.5), 69.7 (13.5), and 61.9 (13.2) L/min, respectively. These flow rates correspond to pressure drops of 5.05 (1.80), 6.52 (2.34) and 5.19 (2.07) kPa, respectively. In total, 380 (99.2%) of patients in the PP population were able to generate a PIF rate through the EH of ≥30 L/min, which is required to enable consistent dose delivery from the DPI; there was a moderate direct association between age and PIF in younger patients with asthma, but this was inverse and less apparent in adult patients with asthma and/or those with COPD. Height and weight were also moderately correlated with PIF. Stronger associations with PIF were observed for some lung function parameters, particularly native PIF and forced inspiratory vital capacity.ConclusionsOver 99% of patients with asthma and/or COPD were able to inhale through the EH with an adequate PIF rate, irrespective of age, or severity of airway obstruction. This confirms that patients with asthma and/or COPD can achieve inspiratory flows via the EH DPI that are sufficient for its effective use.     

Novel electrocardiographic features in carriers of hypertrophic cardiomyopathy causing sarcomeric mutations

Objectives

The sensitivity and specificity of the conventional 12-lead ECG to identify carriers of hypertrophic cardiomyopathy (HCM) – causing mutations without left ventricular hypertrophy (LVH) has been limited. We assessed the ability of novel electrocardiographic parameters to improve the detection of HCM mutation carriers.

Artefactual effects of lipid-based cell transfection reagents on AbetaPP processing and Abeta production.

The study of amyloidogenic beta-amyloid precursor protein (AbetaPP) metabolism and amyloid beta protein (Abeta) production has been a major focus of Alzheimer's disease (AD) neuropathogenesis research. Cell transfection is a commonly employed method for assessing the effects of various genes on AbetaPP processing and Abeta production. Certain cell transfection reagents utilize lipid-based formulations that could potentially affect AbetaPP processing and Abeta production. Thus, we set out to assess the effects of cell transfection reagents with lipid formulations (TKO, FuGene6, RNAifect) on AbetaPP processing and Abeta level in H4 human neuroglioma cells overexpressing human AbetaPP. We found both TKO and RNAifect increase the protein levels of AbetaPP-C-terminal fragments (CTFs) and Abeta levels, while FuGene6 increases the protein levels of AbetaPP-CTFs without altering Abeta level. In contrast, electroporation-based cell transfection does not affect AbetaPP processing and Abeta production in our studies. These results suggest for the first time that lipid-based cell transfection reagents may artefactually affect AbetaPP processing and Abeta production, thereby confounding studies aimed at assessing the effects of transfected genes on AbetaPP metabolism.     

Sustained remission and reduced radiographic progression with combination disease modifying antirheumatic drugs in early rheumatoid arthritis

OBJECTIVE: To study sustainability of remission and good treatment response, and the association of both with radiographic progression, in early rheumatoid arthritis (RA) in the Finnish Rheumatoid Arthritis Combination Therapy trial (FIN-RACo). METHODS: Patients were randomized to receive either a combination of disease modifying antirheumatic drugs (DMARD; COMBI, n = 97) or a single DMARD (SINGLE, n = 98). Remission was defined according to modified American College of Rheumatology (ACR) remission criteria and Disease Activity Score 28 joint count (DAS28) < or = 2.6, and sustained remission as presence of remission at 6, 12, and 24 months. Good treatment response was defined as DAS28 (3/4) 3.2 and decrease of DAS28 >1.2. RESULTS: In 169 patients with complete data, 33 (42%) COMBI and 18 (20%) SINGLE patients achieved modified ACR remission at 2 years, which was sustained in 11 (14%) COMBI and 3 (3%) SINGLE patients. Fifty-four (68%) COMBI and 37 (41%) SINGLE patients were in DAS28 remission at 2 years, which was sustained in 40 (51%) COMBI and 14 (16%) SINGLE patients. Good treatment response was sustained in 67% of COMBI and 27% of SINGLE patients. Over 2 years, the Larsen score increased by a median of 1 (95% CI 0-2) in patients in sustained DAS28 remission compared to 4 (95% CI 2-16) in patients who were in DAS28 remission at 6 months but lost it later; and by 6 (95% CI 2-10) in patients who were not in remission at 6 months. CONCLUSION: A remarkable proportion of patients with early RA treated with combinations of DMARD were in remission at 2 years, and remission was more often sustained compared to patients treated with a single DMARD. Sustained remission protects against radiographic joint damage.