bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the risk of hypoxia in flight: the need for more rational guidelines
Authors: Coker RK , Partridge MR
Published: March 2004

This study aimed to test the hypothesis that advice currently given by respiratory physicians to potentially hypoxic patients planning air travel varies and is not evidence-based. A prospective observational study was performed, surveying respiratory physicians in England and Wales. Sixty-two per cent responded. Nearly two-thirds worked in district general hospitals, a quarter in university hospitals, and the rest in tertiary referral (specialist) centres or a combination thereof. Most provide advice routinely; most of the remainder do on request or if concerned. Assessments comprise spirometry, blood gas level measurement, oximetry, predictive equations and hypoxic challenge tests. Twenty-five per cent of physicians measuring blood gas levels recommend in-flight oxygen when arterial oxygen tension (Pa,O2) <7.3 kPa, 50% when Pa,O2 is 7.3-8.0 kPa. Over two-thirds using spirometry recommend oxygen when the forced expiratory volume in one second <40% of the predicted value. Half recommend oxygen when arterial oxygen saturation (Sa,O2) <90%, 33% when Sa,O2 is 90-94%. Fewer than 10% of district hospital physicians (and none in other hospitals) use predictive equations. More than half of specialists but fewer than 10% of district hospital physicians perform hypoxic challenge tests. The risk of hypoxia at altitude is recognized by most respiratory physicians in England and Wales, but assessment methods and criteria for recommending oxygen vary widely. This suggests that most current advice is not evidence-based. Evidence-based guidelines are required.
Impact of correcting peak flow for nonlinear errors on air pollutant effect estimates from a panel study
Authors: Ward DJ , Miller MR , Walters S , Harrison RM , Ayres JG
Published: March 2004

Air pollutant effects are commonly investigated using panel studies employing daily measurement of changes in peak expiratory flow (PEF). Variable orifice PEF meters are inaccurate with a nonlinear relationship to actual PEF. The impact on a panel study of correcting these errors was examined. Twice-daily PEF readings were taken by 147 9-yr old children for 8 weeks and corrected using an equation derived from the response of 32 Vitalograph meters to a servomechanism-controlled pump. Pollutant effect estimates for corrected and uncorrected readings were derived using a regression approach incorporating appropriate confounders. Correction impacted little on mean PEF values (333.1-334.2 L x min(-1)), but did alter effect sizes. Nonsignificant nitrogen dioxide estimates for the entire panel decreased by up to 73%, but, for symptomatic/atopic children, a significant 5-day mean result was lost (decrease in effect size from -2.53 to -0.90% per 10 parts per billion (ppb)) and lag 0 became significant (decrease from -0.51 to -1.22% per 10 ppb). Mass concentration estimates of particles with a 50% cut-off aerodynamic diameter of 2.5 microm moved in both directions (-0.22 changed to 0.11% per 10 microg x m(-1) lag 3 and -0.29 to -0.73% per 10 microg x m(-3) for the 5-day mean). Correction of nonlinearity of peak expiratory flow meters influenced the overall outcome of this panel study, and the changes in effect estimates would be sufficient to alter the interpretation of some studies. For adults, a greater change in effect estimates may follow the larger correction required for their usual peak expiratory flow range.
Sodium channel blockers and uridine triphosphate: effects on nasal potential difference in cystic fibrosis mice
Authors: Ghosal S , Taylor CJ , Colledge WH , Ratcliff R , Evans MJ
Published: March 2004

Sodium channel inhibitors block the enhanced Na+ reabsorption in cystic fibrosis (CF). Extracellular nucleotides facilitate Cl- secretion via Ca2+ gated Cl- channels. A combination of these effects may produce less viscid secretions in CF which are easier to expectorate. This study examined the effects of combining sodium channel blockers with uridine triphosphate (UTP) on nasal membrane potential difference (PD) in CF insertional null mutant mice (cftr(tm1HGU)), deltaF508 homozygous mice (cftr(tm1Cam)) and matched control animals. Median basal PD in the insertional CF mice and deltaF508 CF mice were -28 and -34 mV respectively. These values were significantly different to the control animals (-20 mV). Amiloride and loperamide reduced the PD in cftr(tm1HGU) CF mice (deltaPD 13 mV & 15 mV respectively) suggesting Na+ blockade. The subsequent addition of UTP in a chloride-free vehicle increased the PD (deltaPD -8- -12.5 mV). DeltaF508 mice showed significantly greater responses compared with CF insertional null mutant mice (p<0.05). The action of UTP was brief and not prolonged by the addition alpha-beta-methylene-adenosine 5' diphosphate. Suramin, a competitive antagonist of P2 purinoceptors blocked the action of UTP. In conclusion, this study demonstrated dose dependant nasal membrane potential changes in differences mice with uridine triphosphate in the presence of sodium channel blockers suggestive of chloride secretion. More stable analogues of uridine triphosphate in combination with long acting sodium channel blockers such as loperamide may have therapeutic potential in cystic fibrosis.
The association between early life lung function and wheezing during the first 2 yrs of life
Authors: Young S , Arnott J , O'Keeffe PT , Le Souef PN , Landau LI
Published: March 2004

Reports have suggested that certain infants are predisposed to wheezing in the first 2 yrs of life due to abnormal lung function, prior to the first wheezing illness. The authors investigated the association between infant lung function and wheeze during the first 2 yrs of life. A cohort of 253 infants was evaluated. Respiratory function assessment was performed at 1, 6, and 12 months of age. Parental history of asthma, atopy, and maternal antenatal smoking habits were recorded. An infant was identified as having wheezed on the basis of parental report and, where possible, physician diagnosis. One hundred and sixty infants (63%) had complete diary and questionnaire information on wheeze available for analysis. Of these: 79 infants (50%) had never wheezed (NW) during the first 2 yrs of life and 81 had reported wheeze (W) (50%). Of those with a report of wheeze, the distribution through the first 2 yrs of life was; 28 during the first year of life only (Y1), 21 in the second year of life only (Y2), and 32 wheezed in both the first and second years of life (Y1&2). At the age of 1 month, prior to any lower respiratory illness, the W group had impaired lung function in comparison to the NW group. In Y1 infants, the neonatal lung function differences resolved by 12 months of age. In Y2 and Y1&2 infants lung function differences persisted throughout the first year of life. Prevalence of parental asthma and maternal antenatal smoking was increased in the W group p=0.001, p=0.008, respectively), in comparison to the NW infants. Maternal antenatal smoking prevalence was increased in the Y2 and Y1&2 infants in comparison to the NW group (p=0.04), (p=0.01), respectively. Wheezing during the first year of life is often a transient condition which improves with time. It appears to be related to early life reduced small airway calibre. Wheezing that begins or persists into the second year of life is usually associated with a different abnormality of the airways. Commencement or persistence of wheeze into the second year of life may be part of the clinical entity recognized as asthma.
Maturational changes of endothelial vasoactive factors and pulmonary vascular tone at birth
Authors: Levy M , Souil E , Sabry S , Favatier F , Vaugelade P , Mercier JC , Dall'Ava-Santucci J , Dinh-Xuan AT
Published: March 2004

The aim of this study was to determine which endothelial factors were involved in the decrease of pulmonary vascular resistance at birth, and how they changed with maturation. Response of intrapulmonary artery rings precontracted with prostaglandin F2alpha were studied from piglets aged <2 h, 2-3 day, 10 day and adult pigs for pharmacological responses to acetylcholine (ACh) and cromakalim (CMK) in the presence and the absence of the nitric oxide synthase (NOS) inhibitor, N(omega)-nitro-L-arginine (L-NA), the adenosine triphosphate sensitive potassium (K(ATP)) channel blocker, glibenclamide and the endothelin (ET)-A receptor antagonist, BQ123. In situ hybridization and immunochemistry studies were performed in lung tissues of the same animals in order to determine the expression of NOS and ET. There was a small contractile effect of ACh in the newborn. Relaxation to ACh, which was blocked by L-NA and reduced by glibenclamide, only appeared from the age of 3 days. The significantly greater relaxation to CMK in rings without endothelium (p<0.05) was abolished by BQ123 in the newborn, and then disappeared by 2 days of age. Glibenclamide had a greater inhibitory effect on relaxation induced by CMK at 10 days than in the newborn and 2 days old piglets. NOS expression was low in pulmonary arteries of the newborn and increased by 2 days of age whereas the converse was seen with ET expression. It is concluded that: 1) relaxant response to acetylcholine was absent at birth and appeared at 2 days; 2) the reduced relaxant response to cromakalin in rings with endothelium at birth could be blocked by BQ123; and 3) the expression of endothelin decreased whereas the expression of nitric oxide synthase increased from birth to 2 days of age.
Release of endothelins and platelet-activating factor by a rat pleural mesothelial cell line
Authors: Kimura I , Sakamoto Y , Shibasaki M , Kobayashi Y , Matsuo H
Published: March 2004

Thrombin is a multifunctional serine protease. It is generated in inflammatory processes and induces the proliferation and chemotaxis of a variety of cells including mesothelial cells (MTCs). MTCs are epithelial cells derived from the mesoderm, as are the vascular endothelial cells. Since thrombin acts on endothelial cells to produce platelet-activating factor (PAF) and endothelin (ET)-1, it was hypothesized that MTCs also produce PAF and ET via the action of thrombin. Rat pleural MTC (RMTC, 4/4 R.M.-4) monolayers were cultural in tissue culture dishes for various periods. The supernatants were fractionated by means of high-performance liquid chromatography to determine the ET isoforms and PAF species present. Immunoreactive ET was measured using an enzyme-linked immunosorbent assay, and PAF was measured by means of a bioassay using a platelet aggregometer. ET-1, ET-2 and ET-3 were detected in RMTC-conditioned medium, and the predominant isoforms were ET-1 and ET-2. RMTCs mainly released C16:0 PAF into the supernatant. Immunoreactive ET and PAF were released via the action of thrombin. Synthetic PAF significantly induced secretion of ET, but the PAF receptor antagonists, WEB2086 and E6123, failed to modulate thrombin-induced ET release. These results indicate that thrombin acts on pleural rat mesothelial cells to release ET and PAF, which may play a role in the development of pleurisy.
A simplified method for monitoring respiratory impedance during continuous positive airway pressure
Authors: Navajas D , Duvivier C , Farre R , Peslin R
Published: March 2004

The forced oscillation technique is useful in detecting changes in upper airway obstruction in patients with sleep apnoea undergoing continuous positive airway pressure (CPAP) ventilation. The aim of this study was to implement and evaluate a method for estimating respiratory impedance (Zrs) from the pressure and flow recorded at the inlet of the CPAP tubing. The method is based on correcting impedance measured at the inlet of the CPAP tubing (Zi) for the effect of the tubing and the exhalation port. The method was evaluated in mechanical analogues and in a healthy subject. Sinusoidal oscillation of 5, 10 and 20 Hz were superimposed on CPAP (5-15 cmH2O). At 5 Hz, the changes in airflow obstruction were substantially underestimated by Zi. Furthermore, Zi exhibited a negative dependence on Zrs at 20 Hz. The assessment of Zrs was greatly improved after correcting Zi for the effects of the CPAP tubing and the exhalation port. Zrs was well estimated at low frequencies, reaching very high values during total occlusion (>60 cmH2O x s x L(-1) at 5-10 Hz). These results indicate that changes in airflow obstruction can be detected using the forced oscillation technique from pressure and flow recorded on the continuous positive airway pressure device. This facilitates the clinical application of the forced oscillation technique for monitoring upper airway patency during sleep.
Shortening the duration of treatment for cervical tuberculous lymphadenitis
Authors: van Loenhout-Rooyackers JH , Laheij RJ , Richter C , Verbeek AL
Published: March 2004

The aim of the study was to determine the optimal duration of treatment for patients with tuberculous lymphadenitis. The Medline database was searched for relevant articles published between 1978-1997. Inclusion criteria were study populations of patients with predominantly cervical tuberculous lymphadenitis in whom the diagnosis had been confirmed bacteriologically and/or histologically, or was made probable by using clinical and laboratory markers. Treatment management had to include at least isoniazid, rifampicin and pyrazinamide and a follow-up of at least 12 months after the end of treatment. Patients with resistance to rifampicin and pyrazinamide and previous treatment for tuberculosis were excluded. The number of patients who relapsed after treatment was calculated. The study population in eight out of the 35 articles retrieved were suitable for analysis. Some concerned comparative studies. There were eight treatment schedules of 6 months' duration and three schedules of 9 months' duration. Treatment for 6 months resulted in a tuberculous lymphadenitis relapse rate of 13/422=3.3% (95% confidence interval: 1.7-5.5), with a mean follow-up of 31 months after completion of treatment. Treatment for 9 months resulted in a relapse rate of 3/112=2.7% (95% confidence interval: 0.6-7.8), with a mean follow-up of 20 months. Despite the limitations of the literature available, 6 months of therapy is probably sufficient for patients with tuberculous lymphadenitis.
Granulomatous Pneumocystis carinii pneumonia in Wegener's granulomatosis
Authors: Ullmer E , Mayr M , Binet I , Ebnother-Staub C , Dalquen P , Soler M , Tamm M
Published: March 2004

This study reports on a first case of granulomatous Pneumocystis carinii pneumonia (PCP) in a human immunodeficiency virus-negative patient with antineutrophil cytoplasmic antibody-positive Wegener's granulomatosis whilst receiving immunosuppressive treatment. The patient presented with diffuse alveolar haemorrhage, pauci-immune rapid progressive glomerulonephritis and leukocytoclastic vasculitis of the skin. Granulomatous Pneumocystis carinii pneumonia developed under immunosuppressive treatment with cyclophosphamide and prednisone. At the time Pneumocystis carinii pneumonia developed, there was a marked lymphopenia with a very low CD8+ cell count in the blood. Grocott staining in bronchoalveolar lavage fluid revealed no Pneumocystis carinii. The diagnosis was made via a video-assisted thoracoscopic lung biopsy which showed granulomas containing high numbers of Pneumocystis carinii cysts.
Fcγ receptor signaling in primary human microglia: differential roles of PI-3K and Ras/ERK MAPK pathways in phagocytosis and chemokine induction
Authors: Song Xianyuan , Tanaka Sakae , Cox Dianne , Lee Sunhee C
Published: March 2004

Cryptococcus neoformans monoclonal antibody immune complex (IC) induces β-chemokines and phagocytosis in primary human microglia via activation of Fc receptor for immunoglobulin G (FcγR). In this report, we investigated microglial FcγR signal-transduction pathways by using adenoviral-mediated gene transfer and specific inhibitors of cell-signaling pathways. We found that Src inhibitor PP2 and Syk inhibitor piceatannol inhibited phagocytosis, macrophage-inflammatory protein-1α (MIP-1α) release, as well as phosphorylation of extracellular-regulated kinase (ERK) and Akt, consistent with Src/Syk involvement early in FcγR signaling. Constitutively active mitogen-activated protein kinase kinase (MEK) induced MIP-1α, and Ras dominant-negative (DN) inhibited IC-induced ERK phosphorylation and MIP-1α production. These results suggest that the Ras/MEK/ERK pathway is necessary and sufficient in IC-induced MIP-1α expression. Neither Ras DN nor the MEK inhibitor U0126 inhibited phagocytosis. In contrast, phosphatidylinositol-3 kinase (PI-3K) inhibitors Wortmannin and LY294002 inhibited phagocytosis without affecting ERK phosphorylation or MIP-1α production. Conversely, Ras DN or U0126 did not affect Akt phosphorylation. Together, these results demonstrate distinct roles played by the PI-3K and Ras/MEK/ERK pathways in phagocytosis and MIP-1α induction, respectively. Our results demonstrating activation of functionally distinct pathways following microglial FcγR engagement may have implications for human central nervous system diseases.
Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens
Authors: Chelvarajan R L , Collins S M , Doubinskaia I E , Goes S , Van Willigen J , Flanagan D , de Villiers W J S , Bryson J S , Bondada S
Published: March 2004

Neonates do not respond to thymus-independent (TI) antigens (Ag), making them vulnerable to infection with encapsulated bacteria. The antibody (Ab) response of adult and neonatal B cells to TI Ag requires certain cytokines, which are provided by T cells or macrophages (MΦ). Lipopolysaccharide (LPS) failed to induce neonatal MΦ to produce interleukin (IL)-1β and tumor necrosis factor α (TNF-α) mRNA and to secrete IL-1β, IL-12, and TNF-α. However, LPS induced neonates to secrete some IL-6 and three- to fivefold more IL-10 than adults. Accordingly, adding adult but not neonatal MΦ could restore the response of purified adult B cells to trinitrophenol (TNP)–LPS, a TI Ag. Increased IL-10 is causally related to decreased IL-1β and IL-6 production, as IL-10−/− neonatal MΦ responded to LPS by secreting more IL-1β and IL-6 than wild-type (WT) neonatal MΦ. When cultures were supplemented with a neutralizing Ab to IL-10, WT neonatal MΦ secreted increased amounts of IL-6 and allowed neonatal MΦ to promote adult B cells to mount an Ab response against TNP–LPS. Thus, neonates do not respond to TI Ag as a result of the inability of neonatal MΦ to secrete cytokines, such as IL-1β and IL-6, probably as a result of an excess production of IL-10. This dysregulated cytokine secretion by neonatal MΦ may be a result of a reduction in expression of Toll-like receptor-2 (TLR-2) and TLR-4 and CD14.
Endogenously oxidized mitochondrial DNA induces in vivo and in vitro inflammatory responses
Authors: Collins L Vincent , Hajizadeh Shahin , Holme Elisabeth , Jonsson Ing-Marie , Tarkowski Andrej
Published: March 2004

We report that mitochondrial DNA (mtDNA) is inflammatogenic in vitro and in vivo as a result of the presence of unmethylated CpG sequences and its oxidative status. Purified human and murine mtDNAs induced arthritis when injected intra-articularly (i.a.) in mice. Importantly, oligodeoxynucleotide that contained a single oxidatively damaged base also induced arthritis when injected i.a. in mice. In contrast, neither human nor murine nuclear DNA induced inflammation. mtDNA-induced arthritis was neither B cell- nor T cell-dependent but was mediated by monocytes/macrophages. mtDNA-induced nuclear factor-κB stimulation resulted in the production of tumor necrosis factor α, a potent, arthritogenic factor. Finally, extracellular mtDNA was detected in the synovial fluids of rheumatoid arthritis patients but not of control subjects. We conclude that endogenous mtDNA displays inflammatogenic properties as a result of its content of unmethylated CpG motifs and oxidatively damaged adducts.
Effects ofcis-resveratrol on inflammatory murine macrophages: antioxidant activity and down-regulation of inflammatory genes
Authors: Leiro José , Álvarez Ezequiel , Arranz Juan A , Laguna Reyes , Uriarte Eugenio , Orallo Francisco
Published: March 2004

This study investigated for the first time the effects of the cis isomer of resveratrol (c-RESV) on the responses of inflammatory murine peritoneal macrophages, namely on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) during the respiratory burst; on the biosynthesis of other mediators of inflammation such prostaglandins; and on the expression of inflammatory genes such as inducible nitric oxide synthase (NOS)-2 and inducible cyclooxygenase (COX)-2. Treatment with 1–100 μM c-RESV significantly inhibited intracellular and extracellular ROS production, and c-RESV at 10–100 μM significantly reduced RNS production. c-RESV at 1–100 μM was ineffective for scavenging superoxide radicals (O2•−), generated enzymatically by a hypoxanthine (HX)/xanthine oxidase (XO) system and/or for inhibiting XO activity. However, c-RESV at 10–100 μM decreased nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase activity in macrophage homogenates. c-RESV at 100 μM decreased NOS-2 and COX-2 mRNA levels in lipopolysaccharide (LPS) interferon gamma (IFN-γ)-treated macrophages. At 10–100 μM, c-RESV also significantly inhibited NOS-2 and COX-2 protein synthesis and decreased prostaglandin E2 (PGE2) production. These results indicate that c-RESV at micromolar concentrations significantly attenuates several components of the macrophage response to proinflammatory stimuli (notably, production of O2•− and of the proinflammatory mediators NO• and PGE2).
Efficacy of leukocyte depletion of residual pump blood
Authors: Heerdt E M , Fransen E J , Maessen J G , de Jong D S
Published: March 2004

In this study, we examined whether leukocyte depletion from the residual heart-lung machine blood at the end of cardiopulmonary bypass (CPB) has an effect on the leukocyte counts in the systemic circulation.

Twenty-six patients undergoing coronary artery bypass grafting (CABG) were randomly allocated to a leukocyte-depletion group or a control group. In the leukocyte-depletion group ( n = 13), all residual blood (400 mL to 1.4 L) was filtered by leukocyte-removal filters (Pall RS01) and reinfused to the patient after CPB, whereas, in the control group, an identical amount of residual blood after bypass was reinfused without filtration ( n = 13). Leukocyte-depleted allogeneic blood was transfused if needed.

Preoperative risk profiles, pump support and duration of aortic crossclamping time were identical in both patient groups (ns). Leukocyte depletion removed more than 96% of leukocytes from the residual retransfused blood ( p < 0.01) and significantly reduced circulating leukocytes ( p < 0.05) compared with the control group. Remarkably, lower numbers of circulating leukocytes were found, not at 1 hour after reinfusion, but at 4 and 8 hours after reinfusion ( p < 0.05). There were no statistical differences between the two groups with respect to postoperative blood loss, the number of transfused packed red cells and mechanical ventilation time.

These results show that leukocytes can be removed from the residual blood of the heart-lung machine after CPB very effectively. Furthermore, this leukocyte depletion results in a long-term effect, the clinical significance of which has to be elucidated in ongoing studies.
Optimizing cardioplegia strategy for donor hearts
Authors: Johnson Charles E , Faulkner Sherry C , Tucker Juan , Schmitz Michael L , Mee Roger BB , Drummond-Webb Jonathan J
Published: March 2004

Variability in organ preservation strategy has thus far prevented meaningful analysis of clinical donor heart cardioplegia strategies. This paper describes our donor heart procurement protocol, techniques, and recovery team responsibilities. We present 21 patients receiving cardiac transplantation at our institution with an adopted cardioplegia protocol. The procurement team perfusionist ensures consistent attention to myocardial protection with standards that are similar to those applied to native hearts for all congenital heart surgeries.
Experience with the Jostra Rotaflow and QuadroxD oxygenator for ECMO
Authors: Horton S , Thuys C , Bennett M , Augustin S , Rosenberg M , Brizard C
Published: March 2004

Since April 1988, we have been able to offer extracorporeal membrane oxygenation (ECMO) to patients who are either failing ventilation or who need cardiopulmonary support following cardiac surgery. During this time, we have supported 211 patients, the majority of whom have been supported with the Avecor (Affinity, Avecor Cardiovascular Inc., Minneapolis, MN, USA) spiral wound silicone-membrane oxygenator. Microporous hollow-fibre oxygenators have been used (18%) at our center. However, due to their early failure, they have necessitated conversion to a device that potentially would last for the entire ECMO course, i.e., Avecor and, subsequently, have not been used routinely until the introduction of the QuadroxD (Jostra Medizintechnik AG, Hirrlingen, Germany). The recent development of the poly-4-methyl-1-pentene diffusion membrane allows us to utilize hollow-fibre technology with a true (nonmicroporous) membrane. This has enabled us to use this low-resistance device with all its inherent advantages, without plasma leakage necessitating circuit changeover. From July 2000, we have used the QuadroxD oxygenator for our patients requiring ECMO support. This has been in patients with weights ranging from 2.16-51.0 kg ( n = 23), with the longest support being for 1119 hours. This new technology has enabled us to utilize a single device for all patient sizes, so we now have an ECMO circuit set up at all times, minimizing the time required for support to be available, potentially improving survivor morbidity.
Does the use of leucocyte depletion during cardiopulmonary bypass affect exhaled nitric oxide production?
Authors: Sheppard S V , Gibbs R V , Smith D C
Published: March 2004

Fifty patients undergoing elective coronary revascularisation were prospectively randomised to receive either a leucocyte-depleting or a control filter inserted into the arterial line of the cardiopulmonary bypass (CPB) circuit. The concentration of exhaled nitric oxide (NO) was measured 15 min before and 30 min after CPB using a real-time chemiluminescence analyser (Logan Research, Northampton, UK). The baseline rate of exhaled NO production was 2.14±0.83 ppb/s in the control group, and 2.58±0.53 ppb/s in leucocyte-depleted group ( p = 0.17). Following CPB, the mean rate of exhaled NO production in the control group had increased by 1.51±0.45 ppb/s to 3.65±0.81 ppb/s and in the leucocyte-depletion group had increased by 1.05±0.45 ppb/s to 3.64±0.62 ppb/s. The increase in exhaled NO production was significantly lower in the leucocyte depleted group ( p = 0.002), indicating that leucocyte depletion suppressed the increase in exhaled NO production seen following CPB.
Repair of the aortic arch with left unilateral selective cerebral perfusion
Authors: Akgul Ahmet , Ozatik Mehmet Ali , Kucuker Seref Alp , Bahar Ilknur , Tasdemir Oguz
Published: March 2004

A 67-year-old woman who presented with chest and back pain was diagnosed with an aneurysm of the ascending aorta. Coronary angiography and aortography were performed via the right brachial artery, which was complicated by axillary artery dissection. At surgery, despite our clinical experience of using the right upper brachial artery for arterial cannulation, right femoral artery cannulation was performed to establish cardio-pulmonary bypass (CPB) as the dissection was extending to the brachiocephalic artery. The aortic crossclamp was placed on the arch of the aorta just after the origin of the brachiocephalic artery so that cerebral perfusion was performed via the left common carotid and left vertebral and basilar arteries through the left subclavian artery. No neurologic event was observed during the intensive care unit stay and follow-up period. To the best of our knowledge, the literature contains no other report of the use of only the left carotid and subclavian arteries to perfuse cerebral structures during CPB.
ABO-incompatible heart transplantation: a perfusion strategy
Authors: Foreman C , Gruenwald C , West L
Published: March 2004

Infants with fatal cardiac disease often die awaiting transplantation because of the shortage of donor hearts. The Hospital for Sick Children (HSC), Toronto, Canada, has researched and applied the concept of crossing the blood group compatibility barrier. Heart transplantation at HSC unrestricted by ABO compatibility greatly contributed to decreasing the mortality rate among infants on the waiting list from 58% to 10%.

From January 1996 to January 2002, 16 infants less than 14 months of age received ABO-incompatible heart transplants at our institution.

The cardiopulmonary bypass (CPB) circuit is primed with additional volume to replace the patient’s blood volume. Packed red blood cells (PRBC) used in priming must be ABO-compatible with the recipient. All plasma components and platelets must contain no anti-A or anti-B antibodies to donor or recipient. CPB is initiated and the patient’s venous blood is collected into a transfusion bag and sent to the blood bank. The total amount collected should be one and a half to two times the patient’s blood volume. The plasma is separated and discarded, returning only the PRBC, thus reducing the concentration of circulating antibodies to blood group antigens.

Our team has experienced an 87% survival rate with this technique. The success is believed to be associated with the recipients’ immunologic immaturity. Newborns do not produce isohemagglutinins, and serum anti-A and anti-B antibody titers usually remain low until 12-14 months of age. The complement system is not fully developed, therefore, the mediators of hyperacute rejection are absent during early infancy.

Heart transplantation unrestricted by the need for ABO compatibility would effectively expand the available donor pool and decrease waiting times.
In vitro assessment of the unloading and perfusion capacities of the PUCA II and the IABP
Authors: Vandenberghe Stijn , Segers Patrick , Josemans Hans , Van Loon Jan-Paul , Rakhorst Gerhard , Verdonck Pascal
Published: March 2004

The PUCA II pump is a minimally invasive intra-arterial left ventricular assist device that can be used as an alternative for the intra-aortic balloon pump (IABP). In this study, we assessed the cardiac unloading and organ perfusion capacities of both PUCA II and IABP in an in vitro set up, consisting of a heart simulator and a silicone arterial tree, mimicking anatomical geometry and flow distribution. The IABP was positioned in the descending aorta, while the PUCA II was tested both in ‘trans-aortic’ and ‘abdominal’ positions. All devices were driven by the same Arrow AutoCat IABP driver at different pump rates. Apart from flow, arterial pressure and pulse pressure, we also calculated haemodynamic indices for myocardial oxygen supply and demand. The ‘abdominal’ PUCA II assist and the IABP both provide mild unloading of the heart, and a limited improvement of arterial pressure and flow. The ‘trans-aortic’ PUCA II assist greatly enhances flow and pressure, but does not unload the heart properly in the tested configuration.
Determinants of antithrombin consumption in cardiac operations requiring cardiopulmonary bypass
Authors: Ranucci Marco , Ditta Antonio , Boncilli Alessandra , Cotza Mauro , Carboni Giovanni , Brozzi Simonetta , Bonifazi Claudio , Tiezzi Alessandra
Published: March 2004

Antithrombin (AT) is a natural anticoagulant that is consumed during cardiac operations with cardiopulmonary bypass (CPB). This study is an observational trial aimed at identifying the factors determining the magnitude of the AT consumption during cardiac operations. Two hundred and fifty consecutive adult patients undergoing cardiac operations with CPB were admitted to the study. Preoperative and intraoperative variables were tested with respect to their role in determining AT activity at the end of the operation. At a univariate analysis, eight predictors of AT activity at the end of the operation have been identified: preoperative AT activity; age; diabetes on medication; preoperative haematocrit value; preoperative dialysis; combined operation; CPB duration; lowest temperature on CPB. A multivariate predictive model was created, and five factors remained as independent predictors of AT activity at the end of the operation: preoperative AT activity ( p = 0.001); age ( p = 0.015); combined operation ( p = 0.014); diabetes ( p = 0.013) and CPB duration ( p = 0.001). On this basis, predictive tables of AT consumption have been established for different combinations of risk factors.
Na+/H+exchange inhibitor cariporide: effects on respiratory dysfunction after cardiopulmonary bypass
Authors: Eichler Wolfgang , Bechtel Matthias JF , Klaus Stephan , Heringlake Matthias , Hernandez Mario , Toerber Kai , Klotz Karl-Friedrich , Bartels Claus
Published: March 2004

The purpose of the present study was to evaluate the potential of the Na+/H+ exchange inhibitor cariporide to protect the lung from injury after cardiopulmonary bypass (CPB). In a randomized placebo-controlled study, 16 pigs were subjected to CPB for 75 min. Administration of vehicle or cariporide (bolus 180 mg, 40 mg/hour) began 30 min pre-CPB and was continued throughout the protocol. The alveolo-arterial O2-gradient (AaDO2), the pulmonary shunt (Qs/Qt), the compliance (Cpl), haemo-dynamic variables and glycerol and water content in lung tissue were measured 10 min before and up to 180 min post-CPB. All animals in the control versus 75% in the cariporide group survived the experiment. At 5 and 60 min post-CPB, the mean AaDO2 and at 5, 60 and 180 min post-CPB, the mean pulmonary vascular resistance index were higher in the cariporide group ( p < 0.05), respectively. More lung water accumulation was found in the cariporide group ( p < 0.05). Mean Cpl decreased; the Qs/Qt and glycerol in lung tissue increased without significant intergroup difference. In this model, the inhibitor of the Na+/H+ antiporter showed no protective effect on lung injury after CPB and might even have harmful effects on pulmonary vascular tone and function.
Test rig and software for recording force and muscle activity
Authors: Outten Alan G , Cullen Gerard , Stokes Maria J
Published: March 2004

Objective: To design a test rig for measuring isometric quadriceps' force which is easily adjustable, dismountable, transportable, relatively lightweight and inexpensive. Also to produce a data-acquisition software program that enables real-time feedback of the force signal, automatic analysis of maximal voluntary contraction (MVC) force, and submaximal target levels to be displayed on a computer screen, as well as acquisition of other signals such as electromyographic (EMG) activity.

Methodology: A test rig was constructed using an aluminium tubing system which was fully adjustable and could be flat-packed for transportation. The data acquisition software program was written in Borland C++ and is suitable for use with an IBM-compatible PC. The interface is user friendly, and the entire testing system is relatively inexpensive compared to commercially available systems.

Conclusions: The equipment is suitable for various applications in rehabilitation research and clinical testing, and is suitable for examining different muscles. Further technical details are freely available from the authors.
Botulinum toxin type A and short-term electrical stimulation in the treatment of upper limb flexor spasticity after stroke: a randomized, double-blind, placebo-controlled trial
Authors: Hesse Stefan , Reiter Frank , Konrad Matthias , Jahnke Matthias T
Published: March 2004

Objective: To investigate whether the combined approach of botulinum toxin type A (BtxA) and electrical stimulation was more effective than the toxin alone in the treatment of chronic upper limb spasticity after stroke.

Design: Randomized, placebo-controlled study with four treatment groups: 1000 units BtxA (Dysport®) + electrical stimulation (A), 1000 units BtxA (B), placebo + electrical stimulation (C) and placebo (D).

Setting: A neurological rehabilitation clinic.

Subjects: Twenty-four stroke patients with chronic upper limb spasticity after stroke, six patients in each treatment group.

Interventions: Intramuscular injection of either toxin or placebo into six upper limb flexor muscles. In group A and C additional electrical stimulation of the injected muscles with surface electrodes, three times half an hour each day for three days.

Main outcome measures: Muscle tone rated with the modified Ashworth score, limb position at rest and difficulties encountered during three upper limb motor tasks assessed before and 2, 6 and 12 weeks after injection.

Results: Most improvements were observed in patients of group A. Cleaning the palm ( p = 0.004) differed across groups. Pairwise comparison for this target variable showed that group A differed from group B and D ( p <0.01), but not from C. Indicative across-group differences were obtained for elbow spasticity reduction ( p = 0.011), and improvement of putting the arm through a sleeve ( p = 0.020).

Conclusions: The placebo-controlled trial favours the conceptthat electrical stimulation enhances the effectiveness of BtxA in the treatment of chronic upper limb flexor spasticity after stroke.
Alternatives for measuring knee extension strength of the elderly at home
Authors: Bohannon Richard W
Published: March 2004

Objective: To examine the construct validity of three measures of knee extension strength obtained from elderly individuals.

Design: Retrospective and cross-sectional.

Setting: Home care.

Subjects: Forty-one consecutively treated patients (mean age 79.2 years).

Measures: Knee extension strength was measured using manual muscle testing, hand-held dynamometry, and the sit-to-stand test.

Results: Convergent construct validity was supported by the significant correlations between the measures ( r s = 0.578–0.702). Discriminant construct validity was confirmed by the finding of significant differences in the manual muscle test scores and in the hand-held dynamometer measures of patients who were unable versus able to stand from a chair without the upper extremities or help. The sensitivity of the two measures for discriminating between patients able versus unable to stand from a chair was 90.9% for manual testing and 68.2% for dynamometry. The specificity was 78.9% for manual testing and 94.7% for dynamometry.

Conclusion: The results of this study show that the three measures employed to characterize knee extension strength are valid when employed with elderly patients in a home care setting.
Functional motor abilities of children with cerebral palsy: a systematic literature review of assessment measures
Authors: Ketelaar Marjolijn , Vermeer Adri , Helders Paul Jm
Published: March 2004

Objective: To provide an overview of functional assessment measures for children with cerebral palsy, supporting the selection of measures and the interpretation of results from measures.

Methods: Instruments were selected on the basis of a literature search of the Medline, Sportdisk and PsychLIT databases.

Issues reviewed: Instruments were reviewed with respect to target group, purpose, nature, type and psychometric properties.

Results: In the literature 17 instruments that are used in paediatric rehabilitation and paediatric physical therapy to assess the functional motor abilities of children with cerebral palsy were found. While there is an urgent need for measures that can evaluate change in functional abilities, it was found that most measures are developed and validated for discriminative purposes.

Conclusions: Although instruments developed within the lastdecade meet psychometric criteria more adequately than those developed previously, it is concluded that only two evaluative assessment measures, the Gross Motor Function Measure (GMFM) and the Pediatric Evaluation of Disability Inventory (PEDI), fulfil the criteria of reliability and validity with respect to responsiveness to change.
Evaluation of a nurse-led multidisciplinary neurological rehabilitation programme using the Nottingham Health Profile
Authors: Sitzia J , Haddrell V , Rice-Oxley M
Published: March 2004

Objective: To ascertain whether or not an inpatient multidisciplinary treatment programme for patients with Parkinson's disease or multiple sclerosis resulted in a measurable change in patients' health-related quality of life (HRQL).

Design: Assessments of HRQL were made one week before admission and approximately one month post discharge.

Setting: Six-bed Neurological Rehabilitation Unit at Worthing Hospital on the south coast of England.

Subjects: Fifty-eight patients with Parkinson's disease and 33 patients with multiple sclerosis.

Interventions: All patients received an individually adapted, multidisciplinary rehabilitation programme. The programmes lasted from 5 to 10 days.

Main outcome measures: HRQL scores on the Nottingham Health Profile Part 1 (NHP-1).

Results: Overall post-treatment NHP-1 scores were significantly better than overall pretreatment scores for both the Parkinson's group ( z = 2.6, p <0.01) and the multiple sclerosis group ( z = 2.1, p <0.05). Sixty-four per cent of patients perceived an overall improvement. The strongest improvement was in ‘physical mobility’ in the multiple sclerosis group ( z = 3.0, p <0.01) and in ‘emotional reactions' in the Parkinson's group ( z = 2.9, p <0.01).

Conclusions: These results suggest that the multidisciplinary inpatient approach in neurological rehabilitation has identifiable short-term benefits for the majority of patients. A randomized trial with longer follow-up is required to confirm this.
Attachment Relationship Experiences and Childhood Psychopathology
Authors: ZEANAH CHARLES H. , KEYES ANGELA , SETTLES LISA
Published: March 2004

Abstract: Human infants form attachments to their caregivers gradually over the course of the first year of life. Qualitatively different types of attachments, which can be indentified by the end of the first year, are broadly predictive of subsequent adaptive outcomes for young children. “Disorganized” patterns of attachment have the strongest links to concurrent and subsequent psychopathology, and considerable research has demonstrated both within‐the‐child and environmental correlates of disorganized attachment. Clinical disorders of attachment have been demonstrated to arise under conditions of social deprivation, such as institutionalization and maltreatment. An emotionally withdrawn/inhibited pattern and an indiscriminate/disinhibited pattern both have been described. Although these clinical types arise under similar conditions of environmental adversity, they tend to have different courses over time. We describe recent findings and highlight areas of emerging consensus and areas of continuing controversy regarding both disorganized patterns of attachment and clinical disorders of attachment in younbg children.
Social Engagement and Attachment
Authors: PORGES STEPHEN W.
Published: March 2004

Abstract: This article focuses on the importance of social engagement and the behavioral and neurophysiological mechanisms that allow individuals to reduce psychological and physical distance. A model of social engagement derived from the Polyvagal Theory is presented. The model emphasizes phylogeny as an organizing principle and includes the following points: (1) there are well‐defined neural circuits to support social engagement behaviors and the defensive strategies of fight, flight, and freeze; (2) these neural circuits form a phylogenetically organized hierarchy; (3) without being dependent on conscious awareness, the nervous system evaluates risk in the environment and regulates the expression of adaptive behavior to match the neuroception of a safe, dangerous, or life‐threatening environment; (4) social engagement behaviors and the benefits of the physiological states associated with social support require a neuroception of safety; (5) social behaviors associated with nursing, reproduction, and the formation of strong pair bonds require immobilization without fear; and (6) immobilization without fear is mediated by a co‐opting of the neural circuit regulating defensive freezing behaviors through the involvement of oxytocin, a neuropeptide in mammals involved in the formation of social bonds. The model provides a phylogenetic interpretation of the neural mechanisms mediating the behavioral and physiological features associated with stress and several psychiatric disorders.
Family and Community Factors that Predict Internalizing and Externalizing Symptoms in Low‐Income, African‐American Children
Authors: KASLOW NADINE J. , HERON SHERYL , ROBERTS DEBRA KIM , THOMPSON MARTIE , GUESSOUS OMAR , JONES CLAUDIA
Published: March 2004

Abstract: To learn more about the roots of internalizing and externalizing problems in low‐income, African‐American children, aged 8–12 years, particularly for family and community factors, we aimed to determine which variables (mother's psychological functioning, mother's intimate partner violence status [IPV], family cohesion and adaptability, neighborhood disorder) uniquely predicted a child's internalizing distress and externalizing distress, and the amount of variance explained by the model. Results from the regression model predicting internalizing distress indicates that the five predictor variables accounted for 38% of the variance. Two of the five predictors were significantly related to child's internalizing distress scores: mother's intimate partner violence status and maternal psychological distress. Results from the regression model predicting externalizing distress indicates that the five predictor variables accounted for 8% of the variance. The two predictors significantly related to child's externalizing distress scores were levels of family cohesion and maternal psychological distress. Directions for future research and clinical implications are provided.
Aggressive Behavior in Abused Children
Authors: CONNOR DANIEL F. , DOERFLER LEONARD A. , VOLUNGIS ADAM M. , STEINGARD RONALD J. , MELLONI RICHARD H.
Published: March 2004

Abstract: Our objective was to investigate the relationship between a lifetime history of traumatic stress, defined as physical and/or sexual abuse and aggression and psychosocial functioning in a sample of clinically referred and nonclinically referred children and adolescents. This is a retrospective case comparison study. Three groups of children were identified, assessed, matched for age, and partially matched for gender. Children clinically referred to residential treatment with a history of abuse (N= 29) were compared with children clinically referred to residential treatment without a history of abuse (N= 29), and a nonclinical group of children residing in the community (N= 29). Variables investigating specific types of aggression, IQ, and psychopathology were assessed across the three groups. Clinically referred children scored worse on all measures compared with nonclinical community children. Clinically referred abused children scored higher on measures of aggression and significantly higher on measures of reactive aggression and verbal aggression than clinically referred nonabused children. Clinically referred abused children had significantly lower verbal IQ scores than clinically referred nonabused children, but no difference in psychopathology. Results support the importance of assessing specific types of aggression in samples of traumatized youths. Verbal information processing may be especially vulnerable in abused children and adolescents and enhance vulnerability to aggressive responding.