Oxygen transport capacity in the air-breathing fish, Megalops cyprinoides: compensations for strenuous exercise

Tarpon have high resting or routine hematocrits (Hct) (37.6+/-3.4%) and hemoglobin concentrations (120.6+/-7.3 g 1(-1)) that increased significantly following bouts of angling-induced exercise (51.9+/-3.7% and 142.8+/-13.5 g 1(-1), respectively). Strenuous exercise was accompanied by an approximately tenfold increase in blood lactate and a muscle metabolite profile indicative of a high energy demand teleost. Routine blood values were quickly restored only when this facultative air-breathing fish was given access to atmospheric air. In vitro studies of oxygen transport capacity, a function of carrying capacity and viscosity, revealed that the optimal Hct range corresponded to that observed in fish under routine behaviour. During strenuous exercise however, further increase in viscosity was largely offset by a pronounced reduction in the shear-dependence of blood which conformed closely to an ideal Newtonian fluid. The mechanism for this behaviour of the erythrocytes appears to involve the activation of surface adrenergic receptors because pre-treatment with propranolol abolished the response. High levels of activity in tarpon living in hypoxic habitats are therefore supported by an elevated Hct with adrenergically mediated viscosity reduction, and air-breathing behaviour that enables rapid metabolic recovery. (C) 2002 Elsevier Science Inc. All rights reserved.

Impact of on-site testing for maternal syphilis on treatment delays, treatment rates, and perinatal mortality in rural South Africa: a randomised controlled trial

Background: Syphilis remains a significant cause of preventable perinatal death in developing countries with many women remaining untested and thus untreated. Syphilis testing in the clinic (on-site testing) may be a useful strategy to overcome this. We studied the impact of on-site syphilis testing on treatment delays and rates, and perinatal mortality. Methods: We conducted a cluster randomised controlled trial among seven pairs of primary healthcare clinics in rural South Africa, comparing on-site testing complemented by laboratory confirmation versus laboratory testing alone. Intervention clinics used the on-site test conducted by primary care nurses, with results and treatment available within an hour. Control clinics sent blood samples to the provincial laboratory, with results returned 2 weeks later. Results: Of 7134 women seeking antenatal care with available test results, 793 (11.1%) tested positive for syphilis. Women at intervention clinics completed treatment 16 days sooner on average (95% confidence interval: 11 to 21), though there was no significant difference in the proportion receiving adequate treatment at intervention (64%) and control (69%) clinics. There was also no significant difference in the proportion experiencing perinatal loss (3.3% v 5.1%; adjusted risk difference: -0.9%; 95% Cl -4.4 to 2.7). Conclusions: Despite reducing treatment delays, the addition of on-site syphilis testing to existing laboratory testing services did not lead to higher treatment rates or reduce perinatal mortality. However on-site testing for syphilis may remain an important option for improving antenatal care in settings where laboratory facilities are not available.

Cost-effectiveness of psychological and pharmacological interventions for generalized anxiety disorder and panic disorder

Objective: To assess from a health sector perspective the incremental cost-effectiveness of interventions for generalized anxiety disorder (cognitive behavioural therapy [CBT] and serotonin and noradrenaline reuptake inhibitors [SNRIs]) and panic disorder (CBT, selective serotonin reuptake inhibitors [SSRIs] and tricyclic antidepressants [TCAs]). Method: The health benefit is measured as a reduction in disability-adjusted life years (DALYs), based on effect size calculations from meta-analyses of randomised controlled trials. An assessment on second stage filters ('equity', 'strength of evidence', 'feasibility' and 'acceptability to stakeholders') is also undertaken to incorporate additional factors that impact on resource allocation decisions. Costs and benefits are calculated for a period of one year for the eligible population (prevalent cases of generalized anxiety disorder/panic disorder identified in the National Survey of Mental Health and Wellbeing, extrapolated to the Australian population in the year 2000 for those aged 18 years and older). Simulation modelling techniques are used to present 95% uncertainty intervals (UI) around the incremental cost-effectiveness ratios (ICERs). Results: Compared to current practice, CBT by a psychologist on a public salary is the most cost-effective intervention for both generalized anxiety disorder (A$6900/DALY saved; 95% UI A$4000 to A$12 000) and panic disorder (A$6800/DALY saved; 95% UI A$2900 to A$15 000). Cognitive behavioural therapy results in a greater total health benefit than the drug interventions for both anxiety disorders, although equity and feasibility concerns for CBT interventions are also greater. Conclusions: Cognitive behavioural therapy is the most effective and cost-effective intervention for generalized anxiety disorder and panic disorder. However, its implementation would require policy change to enable more widespread access to a sufficient number of trained therapists for the treatment of anxiety disorders.

Teen Triple P: A universal approach to reducing risk factors for behavioural and emotional problems in adolescents at the transition to high school

Teen Triple P is a multilevel system of intervention that is designed to provide parents with specific strategies to promote the positive development of their teenage children as they make the transition into high school and through puberty. The program is based on a combination of education about the developmental needs of adolescents, skills training to improve communication and problem-solving, plus specific modules to deal with common problems encountered by parents and adolescents that can escalate into major conflict and violence. It is designed to increase the engagement of parents of adolescent and pre-adolescent children by providing them with easy access to evidencebased parenting advice and support. This paper presents data collected as part of a survey of over 1400 students in first year high school at 9 Brisbane schools. The survey instrument was constructed to obtain students' reports about behaviour which is known to be associated with their health and wellbeing, and also on the extent to which their parents promoted or discouraged such behaviour at home, at school, and in their social and recreational activities in the wider community. Selected data from the survey were extracted and presented to parents at a series of parenting seminars held at the schools to promote appropriate parenting of teenagers. The objectives were to provide parents with accurate data about teenagers' behaviour, and about teenagers' reports of how they perceived their parents' behaviour. Normative data on parent and teenager behaviour will be presented from the survey as well as psychometric data relating to the reliability and validity of this new measure. Implications of this strategy for increasing parent engagement in parenting programs that aim to reduce behavioural and emotional problems in adolescents will be discussed.

Does egg competition occur in marine broadcast-spawners?

When the availability of sperm limits female reproductive success, competition for sperm, may be an important broker of sexual selection. This is because sperm limitation can increase the variance in female reproductive success, resulting in strong selection on females to compete for limited fertilization opportunities. Sperm limitation is probably common in broadcast-spawning marine invertebrates, making these excellent candidates for investigating scramble competition between broods of eggs and its consequences for female reproductive success. Here, we report our findings from a series of experiments that investigate egg competition in the sessile, broadcast-spawning polychaete Galeolaria caespitosa. We initially tested whether the order in which eggs encounter sperm affects their fertilization success at two ecologically relevant current regimes. We used a split-clutch-split-ejaculate technique to compare the fertilization success of eggs from individual females that had either first access (competition-free treatment) or second access (egg competition treatment) to a batch of sperm. We found that fertilization success depended on the order in which eggs accessed sperm; eggs that were assigned to the competition-free treatment exhibited significantly higher fertilization rates than those assigned to the egg competition treatment at both current speeds. In subsequent experiments we found that prior exposure of sperm to eggs significantly reduced both the quantity and quality of sperm available to fertilize a second clutch of eggs, resulting in reductions in fertilization success at high and low sperm concentrations. These findings suggest that female traits that increase the likelihood of sperm-egg interactions (e.g. egg size) will respond to selection imposed by egg competition.

Achieving the millennium development goals for health - Cost effectiveness analysis of strategies for. maternal and neonatal health in developing countries

Objective To determine the costs and benefits of interventions for maternal and newborn health to assess the appropriateness of current strategies and guide future plans to attain the millennium development goals. Design Cost effectiveness analysis. Setting Two regions classified by the World Health Organization according to their epidemiological grouping: Afr-E, those countries in sub-Saharan Africa with very high adult and high child mortality, and Sear-D, comprising countries in South East Asia with high adult and high child mortality. Data sources Effectiveness data from several sources, including trials, observational studies, and expert opinion. For resource inputs, quantifies came from WHO guidelines, literature, and expert opinion, and prices from the WHO choosing interventions that are cost effective database. Main outcome measures Cost per disability adjusted life year (DALY) averted in year 2000 international dollars. Results The most cost effective mix of interventions was similar in Afr-E and Sear-D. These were the community based newborn care package, followed by antenatal care (tetanus toxoid, screening for pre-eclampsia, screening and treatment of asymptomatic bacteriuria and syphilis); skilled attendance at birth, offering first level maternal and neonatal care around childbirth; and emergency obstetric and neonatal care around and after birth. Screening and treatment of maternal syphilis, community based management of neonatal pneumonia, and steroids given during the antenatal period were relatively less cost effective in Sear-D. Scaling up all of the included interventions to 95% coverage would halve neonatal and maternal deaths. Conclusion Preventive interventions at the community level for newborn babies and at the primary care level for mothers and newborn babies are extremely cost effective, but the millennium development goals for maternal and child health will not be achieved without universal access to clinical services as well.

Management of Patients With Rheumatoid Arthritis in Latin America A Consensus Position Paper From Pan-American League of Associations of Rheumatology and Grupo Latino Americano De Estudio de Artritis Reumatoide

Objective: A consensus meeting of representatives of 18 Latin-American and Caribbean countries gathered in Renaca, Chile, for 2 days to identify problems and provide recommendations for the care of patients with rheumatoid arthritis (RA) in Latin America, a region where poverty and other health priorities make the efforts to provide effective and high quality care difficult. This report includes recommendations for health professionals, patients, and health authorities in Latin America, with an emphasis oil education and therapeutic issues. Methods: Fifty-one rheumatologists (list available only online on the JCR website) from 18 Latin-American and Caribbean countries with a special interest in RA participated in the consensus meeting. Participants were experts identified and appointed by the National Societies of Rheumatology affiliated with the Pan-American League of Associations for Rheumatology (PANLAR) and by the Grupo Latino Americano De Estudio de Artritis Reumatoide (GLADAR)-an independent group of Latin American rheumatologist researchers were also invited to the meeting. Eight topics were identified as priorities: patient, community and allied health professional education, health policy and decision making, programs for early detection and appropriate treatment of RA, role of classic disease modifying antirheumatic drugs (DMARDs), role of biologic therapy, and drug safety surveillance. To reach consensus, a survey with questions relevant to the topic of interest was sent to all participants before the meeting. During a 2 day meeting, the answers of the survey were reviewed and discussed by each group, with final recommendations on action items. Results: The specific topic of the survey was answered by 86% of the participants and 68% of them answered the entire survey. It was agreed that RA and rheumatic diseases which are currently not but should be public health priorities in Latin America, because of their prevalence and impact on quality of life. Conclusions: Strategic areas identified as priorities for our region included: early diagnosis and access to care by multidisciplinary teams, creation of databases to identify infections with the use of biologic agents in RA which are relevant to Latin America, and overall efforts to improve the care of RA patients in accordance with international standards. Implementation of educational programs aimed to improve self-management for patients with RA was also considered crucial.

Growth Hormone Receptor Exon 3 Isoforms and Their Implication in Growth Disorders and Treatment

Human recombinant growth hormone (hGH) has been used to treat short stature in several different conditions, but considerable inter-individual variation in short- and long-term growth response exists. Pharmacogenomics can provide important insights into hGH therapy. The GH receptor (GHR) is the first key molecule mediating GH action. In the past 3 years, a common GHR polymorphism reflecting the presence (GHRf1) or absence (GHRd3) of exon 3 has been under intensive investigation regarding its influence on the response to hGH therapy. Studies that evaluated response to GH treatment determined by these two GHR isoforms in children with GH deficiency, girls with Turner syndrome, children born small for gestational age and patients with acromegaly showed that patients carrying the GHRd3 allele demonstrated a greater GH sensitivity than patients homozygous for the GHRf1 allele. Other studies presented contradictory data, however, which may be caused by confounding factors such as small sample sizes and differences in experimental design. This GHR exon 3 genotype is the first identified genetic factor found to modulate the individual response to GH therapy. This article reviews the historical aspects and pharmacogenetic studies published to date in relation to this GHR polymorphism. The analyses of present and future validation studies may define the use of this and other polymorphisms in clinical practice, moving from pharmacogenetics to routine application and allowing individualization of hGH doses to optimize final outcome. Copyright (C) 2009 S. Karger AG, Basel

Accentuated osteoclastic response to parathyroid hormone undermines bone mass acquisition in osteonectin-null mice

Matricellular proteins play a unique role in the skeleton as regulators of bone remodeling, and the matricellular protein osteonectin (SPARC, BM-40) is the most abundant non-collagenous protein in bone In. the absence of osteonectin, mice develop progressive low turnover osteopenia, particularly affecting trabecular bone. Polymorphisms in a regulatory region of the osteonectin gene are associated with bone mass in a subset of idiopathic osteoporosis patients, and these polymorphisms likely regulate osteonectin expression. Thus it is important to determine how osteonectin gene dosage affects skeletal function. Moreover, intermittent administration of parathyroid hormone (PTH) (1-34) is the only anabolic therapy approved for the treatment of osteoporosis, and it is critical to understand how modulators of bone remodeling, such as osteonectin, affect skeletal response to anabolic agents. In this study, 10 week old female wild type, osteonectin-haploinsufficient, and osteonectin-null mice (C57Bl/6 genetic background) were given 80 mu g/kg body weight/day PTH(1-34) for 4 weeks. Osteonectin gene dosage had a profound effect on bone microarchitecture. The connectivity density of trabecular bone in osteonectin-haploinsufficient mice was substantially decreased compared with that of wild type mice, suggesting compromised mechanical properties. Whereas mice of each genotype had a similar osteoblastic response to PTH treatment, the osteoclastic response was accentuated in osteonectin-haploinsufficient and osteonectin-null mice. Eroded surface and osteoclast number were significantly higher in PTH-treated osteonectin-null mice, as was endosteal area. In vitro studies confirmed that PTH induced the formation of more osteoclast-like cells in marrow from osteonectin-null mice compared with wild type. PTH treated osteonectin-null bone marrow cells expressed more RANKL mRNA compared with wild type. However, the ratio of RANKL:OPG mRNA was somewhat lower in PTH treated osteonectin-null cultures. Increased expression of RANKL in response to PTH could contribute to the accentuated osteoclastic response in osteonectin(-/-) mice, but other mechanisms are also likely to be involved. The molecular mechanisms by which PTH elicits bone anabolic vs. bone catabolic effects remain poorly understood. Our results imply that osteonectin levels may play a role in modulating the balance of bone formation and resorption in response to PTH. (c) 2008 Elsevier Inc. All rights reserved.

Two-stage laparoscopic liver resection for bilateral colorectal liver metastasis

Hepatectomy may prolong the survival of colorectal cancer patients with liver metastases. Two-stage liver surgery is a valid option for the treatment of bilobar colorectal liver metastasis. This video demonstrates technical aspects of a two-stage pure laparoscopic hepatectomy for bilateral liver metastasis. To the authors` knowledge, this is the first description of a two-stage laparoscopic liver resection in the English literature. A 54-year-old man with right colon cancer and synchronous bilobar colorectal liver metastasis underwent laparoscopic right colon resection followed by oxaliplatin-based chemotherapy. The patient then was referred for surgical treatment of liver metastasis. Liver volumetry showed a small left liver remnant. Surgical planning was for a totally laparoscopic two-stage liver resection. The first stage involved laparoscopic resection of segment 3 and ligature of the right portal vein. The postoperative pathology showed high-grade liver steatosis. After 4 weeks, the left liver had regenerated, and volumetry of left liver was 43%. The second stage involved laparoscopic right hepatectomy using the intrahepatic Glissonian approach. Intrahepatic access to the main right Glissonian pedicle was achieved with two small incisions, and an endoscopic vascular stapling device was inserted between these incisions and fired. The line of liver transection was marked following the ischemic area. Liver transection was accomplished with the Harmonic scalpel and an endoscopic stapling device. The specimen was extracted through a suprapubic incision. The falciform ligament was fixed to maintain the left liver in its original anatomic position, avoiding hepatic vein kinking and outflow syndrome. The operative time was 90 min for stage 1 and 240 min for stage 2 of the procedure. The recoveries after the first and second operations were uneventful, and the patient was discharged on postoperative days 2 and 7, respectively. Two-stage liver resections can be performed safely using laparoscopy. The intrahepatic Glissonian approach is a useful tool for pedicle control of the right liver, especially after previous dissection of the hilar plate.

Exhaled nitric oxide for monitoring childhood asthma inflammation compared to sputum analysis, serum interleukins and pulmonary function

The level of fractional exhaled nitric oxide (FENO) is significantly elevated in uncontrolled asthma and decreases after anti-inflammatory therapy The aim of this prospective study was to analyze the behavior of FENO in the follow-up and management of the inflammation in asthmatic pediatric patients treated with inhaled corticosteroids (ICS), compared to sputum cellularity, serum interleukins (IL), and pulmonary function. Twenty-six clinically stable asthmatic children aged from 6 to 18 years, previously treated or not with ICS were included. Following an international consensus (GINA), the patients were submitted to standard treatment with inhaled fluticasone for 3 months according to the severity of the disease. During this period, each patient underwent three assessments at intervals of approximately 6 weeks: Each evaluation consisted of the measurement of FENO, determination of serum interleukins IL-5, IL-10, IL-13, and interferon gamma (INF-gamma), spirometry and cytological analysis of spontaneous or induced sputum. A significant reduction in mean FENO and IL-5, without concomitant changes in FEV1, was observed along the study. There was no significant correlation between FeNO and FEV1 in the three assessments. A significant correlation between FeNO and IL-5 levels was only observed in the third assessment (r = 0.499, P=0.025). In most patients, serum IL-10, IL-13, and INF-gamma concentrations were undetectable throughout the study Sputum samples were obtained spontaneously in 11 occasions and in 56 by induction with 3% hypertonic saline solution (success rate: 50.8%), with 39 (69.9%) of them adequate for analysis. Only two of the 26 patients produced adequate samples in the three consecutive evaluations, which impaired the determination of a potential association between sputum cellularity and FeNO levels throughout the study. In conclusion, among the parameters of this study, it was difficult to perform and to interpret the serial analysis of spontaneous or induced sputum. Serum interleukins, which remained at very low or undetectable levels in most patients, were not found to be useful for therapeutic monitoring, except for IL-5 that seems to present some correlation with levels of FeNO exhaled. Monitoring of the mean FEV1 indicated no significant variations during the treatment, demonstrating that functional stability or the absence of obstruction may not reflect the adequate management of asthma. Serial measurement of FeNO seemed to best reflect the progressive anti-inflammatory action of ICS in asthma.

Pressure-Frequency Sensing Subxiphoid Access System for Use in Percutaneous Cardiac Electrophysiology: Prototype Design and Pilot Study Results

We have designed, built, and tested an early prototype of a novel subxiphoid access system intended to facilitate epicardial electrophysiology, but with possible applications elsewhere in the body. The present version of the system consists of a commercially available insertion needle, a miniature pressure sensor and interconnect tubing, read-out electronics to monitor the pressures measured during the access procedure, and a host computer with user-interface software. The nominal resolution of the system is <0.1 mmHg, and it has deviations from linearity of <1%. During a pilot series of human clinical studies with this system, as well as in an auxiliary study done with an independent method, we observed that the pericardial space contained pressure-frequency components related to both the heart rate and respiratory rate, while the thorax contained components related only to the respiratory rate, a previously unobserved finding that could facilitate access to the pericardial space. We present and discuss the design principles, details of construction, and performance characteristics of this system.