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Biomedical subjects

S J Allen

Publications and source records attributed to S J Allen.

At least 73 records · Page 4Linked to original sources

Contamination of lymph from the major prenodal cardiac lymphatic in dogs.

Cannulation of the canine major prenodal cardiac lymphatic (MPCL) is the most common approach for the investigation of myocardial lymphatic function. However, the assumption that the MPCL drains pure cardiac lymph has been questioned. We studied variations of MPCL anatomy and investigated whether noncardiac lymph is drained by this lymphatic. After dye was injected into the lungs and left ventricular myocardium in 21 dogs, dissection of the cardiac lymphatic system yielded 3 anatomic variations. In variations 1 and 2 (81% of dogs), a mixture of cardiac and pulmonary lymph was drained via the MPCL. In variation 3 (19% of dogs) no connection was found between MPCL and pulmonary lymphatics. In variations 1 and 2, alteration of tidal volume resulted in significant changes of lymph flow rate. The pulmonary contribution to MPCL lymph flow was estimated as 34% in variation 2. We conclude that MPCL lymph may contain not only cardiac lymph but also significant pulmonary contamination. This finding should be considered in the interpretation of lymph data from cannulation of the canine MPCL.

Animals↗

Prevention of cerebral malaria in children in Papua New Guinea by southeast Asian ovalocytosis band 3.

Southeast Asian ovalocytosis (SAO) occurs at high frequency in malarious regions of the western Pacific and may afford a survival advantage against malaria. It is caused by a deletion of the erythrocyte membrane band 3 gene and the band 3 protein mediates the cytoadherence of parasitized erythrocytes in vitro. The SAO band 3 variant may prevent cerebral malaria but it exacerbates malaria anemia and may also increase acidosis, a major determinant of mortality in malaria. We undertook a case-control study of children admitted to hospital in a malarious region of Papua New Guinea. The SAO band 3, detected by the polymerase chain reaction, was present in 0 of 68 children with cerebral malaria compared with six (8.8%) of 68 matched community controls (odds ratio = 0, 95% confidence interval = 0-0.85). Median hemoglobin levels were 1.2 g/dl lower in malaria cases with SAO than in controls (P = 0.035) but acidosis was not affected. The remarkable protection that SAO band 3 affords against cerebral malaria may offer a valuable approach to a better understanding of the mechanisms of adherence of parasitized erythrocytes to vascular endothelium, and thus of the pathogenesis of cerebral malaria.

Animals↗

Beta-blockade as an alternative to cardioplegic arrest during cardiopulmonary bypass.

BACKGROUND: As an alternative to cardioplegic arrest, cardiac surgical conditions have been produced using beta-blocker-induced minimal myocardial contraction (MMC) during cardiopulmonary bypass. The technique of MMC involves the use of high-dose intravenous esmolol to suppress myocardial chronotropy and inotropy sufficiently to produce cardiac surgical conditions. The purpose of this study was to compare conventional crystalloid cardioplegic arrest with MMC in terms of ischemia avoidance, myocardial edema formation, and cardiac function. METHODS: Twelve dogs were placed on cardiopulmonary bypass. Six dogs were subjected to crystalloid cardioplegic arrest for 2 hours. Surgical conditions were produced in the other 6 dogs for 2 hours using intravenous esmolol without aortic clamping or cardioplegia. Arterial and coronary sinus lactate concentrations were determined as a gauge of myocardial ischemia. Myocardial water content was determined using microgravimetry and preload recruitable stroke work was determined using sonomicrometry and micromanometry. RESULTS: Significant lactate washout was demonstrated after cardioplegic arrest but not after MMC. Myocardial water content was significantly less during and after MMC compared with cardioplegic arrest (p < 0.05). Preload recruitable stroke work was decreased compared with baseline values in both groups (p < 0.05). CONCLUSIONS: In contrast to a previous study that involved 1 hour of MMC, in this study, ventricular function was decreased to the same extent as with cardioplegic arrest after 2 hours of MMC. This was attributed to the accumulation of ASL-8123, the primary metabolite of esmolol, which possesses beta-antagonist properties. Although postbypass ventricular function is similar in both groups, MMC appears to be superior in terms of ischemia avoidance and myocardial edema formation.

Adrenergic beta-Antagonists↗

Increasing the colloid osmotic pressure of cardiopulmonary bypass prime and normothermic blood cardioplegia minimizes myocardial oedema and prevents cardiac dysfunction.

UNLABELLED: Our recent work demonstrated that normothermic continuous antegrade blood cardioplegia results in cardiac dysfunction related to myocardial oedema. This oedema was partially due to increased myocardial microvascular fluid filtration induced by crystalloid hemodilution. We hypothesized that increasing the colloid osmotic pressure of blood cardioplegia would stop fluid filtration into the cardiac interstitium, thus preventing myocardial oedema and cardiac dysfunction. METHODS: We determined myocardial water content in six dogs by microgravimetry and myocardial lymph flow from the major prenodal cardiac lymphatic. Preload recruitable stroke work was derived from sonomicrometry and micromanometry. The dogs were subjected to normothermic cardiopulmonary bypass primed with 6% hetastarch and 1 h of normothermic continuous antegrade blood cardioplegia (4:1 blood:6% hetastarch colloid osmotic pressure 21 +/- 2 mmHg) delivered at 50 mmHg perfusion pressure. RESULTS: We found that despite increased colloid osmotic pressure, a small but significant increase in myocardial water content still occurred during blood cardioplegia. As myocardial lymph flow virtually ceased during cardioplegia, myocardial microvascular filtration must have been present. However, increased myocardial lymph flow following cardioplegia resulted in complete oedema resolution associated with normal left ventricular performance post-cardiopulmonary bypass. CONCLUSIONS: Our data show that the plegic myocardium is prone to oedema formation because of both relatively enhanced fluid filtration and lymph flow cessation. We conclude that increasing the colloid osmotic pressure of normothermic blood cardioplegia minimizes myocardial oedema, thus preventing post-cardiopulmonary bypass cardiac dysfunction.

Animals↗

Red cell morphology and malaria anaemia in children with Southeast-Asian ovalocytosis band 3 in Papua New Guinea.

Southeast-Asian ovalocytosis (SAO) was diagnosed in children from Madang, Papua New Guinea, by detection of the SAO band 3 gene variant using the polymerase chain reaction. SAO band 3 was present in 16/241 (6.6%) children living in the community and 32/389 (8.2%) children with acute Plasmodium falciparum malaria (P=0.42). SAO band 3 was detected in 8.2% (23/281) of alpha+-thalassaemia homozygotes, 9.4% (20/214) of heterozygotes and 2.4% (2/85) of children with a normal alpha-globin genotype (P=0.12). The most consistent feature of SAO band 3 on microscopy of thin blood films was red cells with two or more linear or irregularly-shaped pale regions. In children living in the community, these were present in 15 with SAO band 3 (sensitivity 93.8%) and only two normals (specificity 99.1%). The presence of > or = 20% ovalocytosis was a poorer indicator of SAO band 3 (sensitivity 68.8% and specificity 100%). Haematological data were similar in SAO band 3 and normal children. However, in children with acute malaria, haemoglobin levels and red cell counts were significantly lower in SAO band 3 than normal children. The degree of ovalocytosis was lower in children with SAO band 3 during acute malaria, suggesting that a selective loss of ovalocytes may contribute to malaria anaemia in Southeast-Asian ovalocytosis.

Anemia↗

Myocardial fluid balance: pathophysiology and clinical implications.

Excess fluid in the myocardial interstitium is a common manifestation of many clinical states. Extracellular myocardial edema should be a concern for clinicians as it has been demonstrated to produce cardiac dysfunction. This paper will briefly discuss those factors governing myocardial fluid balance and review the evidence of myocardial edema in various diseases.

Animals↗

Current concepts in treatment of closed head injury.

Standards for management of severe closed head injury should help to establish a foundation for routine care and ongoing research. Studies of cerebral blood flow, oxygenation and metabolism suggest a pattern seen in patients with low c\scores on the Glasgow Coma Scale (GCS), who are known to have poor outcomes. Moderate hypothermia, although improving outcome for patients with GCS of 5-7, has not been beneficial for patients with lower GCS scores.

Journal Article↗

Causes of preterm delivery and intrauterine growth retardation in a malaria endemic region of Papua New Guinea.

AIM: To identify causes of preterm delivery and intrauterine growth retardation (IUGR) in a malaria endemic region of Papua New Guinea. METHODS: Independent predictors of preterm delivery and birthweight in term infants were identified using multiple regression analysis in a prospective study of 987 singleton live births delivered in Madang Hospital. RESULTS: Overall, Plasmodium falciparum infection of the placenta was associated with a reduction in birthweight of 130 g. Malaria was significantly more common in primigravidae than multigravidae and probably contributed to both preterm delivery and IUGR. Maternal haemoglobin concentrations were significantly lower in malaria infected than noninfected women and reduced haemoglobin was the main determinant of preterm delivery. Poorer maternal nutritional status and smoking were associated with both prematurity and IUGR. Greater antenatal clinic attendance predicted increased birthweight in term infants. CONCLUSIONS: Protection against malaria during pregnancy, especially in primigravidae, improved nutrition in women and discouragement of smoking would probably reduce both preterm delivery and IUGR. Greater use of existing antenatal clinics might increase birthweight in term infants.

Adult↗

IgG3 antibodies to Plasmodium falciparum merozoite surface protein 2 (MSP2): increasing prevalence with age and association with clinical immunity to malaria.

In a cross-sectional survey carried out in west Africa (The Gambia), where Plasmodium falciparum malaria is endemic with seasonal transmission, 178 individuals 1-75 years of age were assessed for their antibody response to the malaria vaccine candidate, merozoite surface protein 2 (MSP2). Total IgG to recombinant antigens representing full-length, repetitive, and group-specific domains of both allelic families of MSP2 was determined by ELISA. The IgG-subclass profile of IgG-positive sera was assessed. Antibody prevalence was age-dependent, reaching a peak during adolescence. In MSP2-seropositive individuals, there was a predominance of cytophilic antibodies (IgG1 and IgG3); IgG1 antibodies were prevalent in children less than 10 years of age, whereas in adolescents and adults MSP2-specific antibodies were predominantly IgG3. In parallel, we conducted a longitudinal study of children (3-8 years of age) from the same community; sera collected before the malaria transmission season were tested for the presence of anti-MSP2 antibodies. The subsequent susceptibility of these children to clinical malaria was monitored and the association between anti-MSP2 antibodies of different IgG subclasses and resistance to clinical malaria was tested. The presence of IgG3 antibodies to MSP2 serogroup A was negatively associated with the risk of clinical malaria whereas IgG1 antibodies to MSP2 serogroup B were associated with an increased risk of clinical infection. Our data suggest that age/exposure-related acquisition of IgG3 antibodies to MSP2 may contribute to the development of clinically protective immunity to malaria.

Adolescent↗

alpha+-Thalassemia protects children against disease caused by other infections as well as malaria.

In the South West Pacific region, the striking geographical correlation between the frequency of alpha+-thalassemia and the endemicity of Plasmodium falciparum suggests that this hemoglobinopathy provides a selective advantage against malaria. In Vanuatu, paradoxically, alpha+-thalassemia increases the incidence of contracting mild malaria in the first 2 years of life, but severe disease was too uncommon to assess adequately. Therefore, we undertook a prospective case-control study of children with severe malaria on the north coast of Papua New Guinea, where malaria transmission is intense and alpha+-thalassemia affects more than 90% of the population. Compared with normal children, the risk of having severe malaria was 0.40 (95% confidence interval 0.22-0.74) in alpha+-thalassemia homozygotes and 0.66 (0.37-1.20) in heterozygotes. Unexpectedly, the risk of hospital admission with infections other than malaria also was reduced to a similar degree in homozygous (0. 36; 95% confidence interval 0.22-0.60) and heterozygous (0.63; 0. 38-1.07) children. This clinical study demonstrates that a malaria resistance gene protects against disease caused by infections other than malaria. The mechanism of the remarkable protective effect of alpha+-thalassemia against severe childhood disease remains unclear but must encompass the clear interaction between this hemoglobinopathy and both malarial and nonmalarial infections.

Child↗

Reduced cholinergic function in normal and Alzheimer's disease brain is associated with apolipoprotein E4 genotype.

Apolipoprotein E (ApoE) is a potent risk factor for Alzheimer's disease. Since the loss of cholinergic function in Alzheimer's disease is known to occur at an early stage in the disease we have examined this function in normal subjects with an Apoepsilon4 allele to see if the deficit occurs in the absence of Alzheimer pathology or symptoms. We report that brain tissue obtained post-mortem from normal subjects and Alzheimer patients with an Apoepsilon4 allele has a lower cholinergic activity than tissue from those subjects without this allele. This has important significance for the interpretation of the cholinergic deficits found in Alzheimer's disease.

Aged↗

Cooling gradients and formation of gaseous microemboli with cardiopulmonary bypass: an echocardiographic study.

BACKGROUND: Previous studies demonstrated gas emboli formation during rewarming from hypothermia on cardiopulmonary bypass when the temperature gradient exceeded a critical threshold. It also has been suggested that formation of arterial gas emboli may occur during cooling on cardiopulmonary bypass when cooled oxygenated blood exiting the heat exchanger is warmed on mixture with the patient's blood. The purpose of this study was to determine under what circumstances gas emboli formation would occur during cooling on cardio-pulmonary bypass. METHODS: Eight anesthetized mongreal dogs were placed on cardiopulmonary bypass using a roller pump, membrane oxygenator, and arterial line filter. For emboli detection, we positioned a transesophageal echocardiographic probe at the aortic arch distal to the aortic cannula and Doppler probes at the common carotid artery and the arterial line. Cooling gradients between normothermic blood and cooled arterial perfusate of 5 degrees, 10 degrees, 15 degrees, 20 degrees, and 0 degree C (isothermal controls) were investigated. In addition to preestablished temperature gradients, we investigated the effect of rapid cooling (maximal flow through the heat exchanger at a water bath temperature of 4 degrees C) after the initiation of normothermic cardiopulmonary bypass. RESULTS: Minimal gas emboli were detected at the aortic arch at gradients of 10 degrees C or greater. The incidence of emboli was related directly to the magnitude of the temperature gradient (p < 0.01). No emboli were detected at the carotid artery. During rapid cooling, no emboli were observed either at the aorta or at the carotid artery. CONCLUSIONS: Cooling gradients of 10 degrees C or greater may be associated with gas emboli formation, but they may be of limited clinical significance because no emboli were detected distal to the aortic arch. During the application of rapid cooling, no emboli formation was observed.

Animals↗

Immunoglobulin-like domains define the nerve growth factor binding site of the TrkA receptor.

Nerve growth factor (NGF) is involved in the development and maintenance of the nervous system. NGF binds with high affinity to the extracellular region of the tyrosine kinase receptor TrkA. This domain comprises leucine and cysteine rich motifs, followed by two immunoglobulin like (Ig-like) domains. We describe the expression and purification of recombinant Ig-like domains. Fluorescence and circular dichroism spectroscopy show that the protein is folded into a compact globular structure and contains mainly beta-sheet secondary structure. Recombinant protein binds to NGF and can inhibit NGF bioactivity both in vitro and in vivo.

Amino Acid Sequence↗

Augmenting cardiac contractility hastens myocardial edema resolution after cardiopulmonary bypass and cardioplegic arrest.

UNLABELLED: Although myocardial edema is associated with cardiopulmonary bypass (CPB) and cardioplegic arrest (CPA), interventions to expedite edema removal have not been investigated. The primary mechanism for the removal of excess interstitial fluid in the heart is myocardial lymphatic drainage, but lymphatic function can be impaired by decreased contractility because of edema. The purpose of this study was to determine whether enhancing cardiac contractility would increase myocardial lymphatic function and hasten edema resolution after CPB. Sixteen dogs were subjected to CPB and 1 h of hypothermic CPA. After weaning from CPB, 10 dogs received an intravenous dobutamine infusion and 6 dogs received no inotropic support. We determined myocardial lymph driving pressure from the major cardiac lymphatic, myocardial water content by using microgravimetry, and the peak rate of left ventricular pressure increase (dP/dmax) by using micromanometry. Measurements were taken at baseline, during CPA, and 60 min after CPB. Compared with controls, dobutamine-treated dogs had an increased dP/dmax (P < 0.05), which was associated with higher lymph driving pressures (P < 0.05), resulting in lower myocardial water gain 1 h after CPB (P < 0.05). We conclude that the resolution of myocardial edema after CPB was hastened by dobutamine. Organized ventricular contraction and myocardial contractility seem to be important determinants of myocardial lymphatic function and myocardial edema removal. These findings suggest that the administration of inotropic drugs after CPB may hasten cardiac recovery. IMPLICATIONS: Myocardial edema, which develops during cardiopulmonary bypass and cardioplegic arrest, contributes to cardiac dysfunction after heart surgery. This study demonstrated that enhancement of cardiac contractility by the administration of dobutamine after cardiopulmonary bypass and cardioplegic arrest was associated with increased myocardial lymphatic function and hastened edema resolution in dogs.

Animals↗

Effect of body repositioning after venous air embolism. An echocardiographic study.

BACKGROUND: Current therapy for massive venous air embolism (VAE) may include the use of the left lateral recumbent (LLR) position, although its effectiveness has been questioned. This study used transesophageal echocardiography to evaluate the effect of body repositioning on intracardiac air and acute cardiac dimension changes. METHODS: Eighteen anesthetized dogs in the supine position received a venous air injection of 2.5 ml/kg at a rate of 5 ml/ s. After 1 min the dogs were repositioned into either the LLR, LLR 10 degrees head down (LLR-10 degrees), right lateral recumbence, or remained in the supine position. RESULTS: Repositioning after VAE resulted in relocation of intracardiac air to nondependent areas of the right heart. Peak right ventricular (RV) diameter increase and mean arterial pressure decrease were greater in the repositioned animals compared with those in the supine position (P < 0.05). Right ventricular diameter and mean arterial pressure showed an inverse correlation (r = 0.81). Peak left atrial diameter decrease was greater in the LLR and LLR-10 degrees positions compared with the supine position (P < 0.05). Repositioning did not influence peak pulmonary artery pressure increase, and no correlation was found between RV diameter and pulmonary artery pressure. All animals showed electrocardiogram and echocardiographic changes reconcilable with myocardial ischemia. CONCLUSIONS: In dogs, body repositioning after VAE provided no benefit in hemodynamic performance or cardiac dimension changes, although relocation of intracardiac air was demonstrated. Right ventricular air did not appear to result in significant RV outflow obstruction, as pulmonary artery pressure increased uniformly in all groups and was not influenced by the relocation of intracardiac air. The combination of increased RV afterload and arterial hypotension, possibly with subsequent RV ischemia rather than RV outflow obstruction by an airlock appeared to be the primary mechanism for cardiac dysfunction after VAE.

Animals↗

Intratracheal pressure monitoring during synchronized intermittent mandatory ventilation and pressure controlled-inverse ratio ventilation.

OBJECTIVES: To directly measure airway pressures proximal and distal to endotracheal tubes during conventional synchronized intermittent mandatory ventilation (SIMV) and pressure controlled-inverse ratio ventilation (PC-IRV), and to compare them with these values measured by the ventilator. DESIGN: Prospective, nonrandomized study. SETTING: Surgical intensive care unit at a trauma center. PATIENTS: Group 1: Eight intubated adult patients connected to mechanical ventilators in the SIMV mode were studied. All patients required mechanical ventilation following traumatic injuries. Group 2: Five intubated adult patients with adult respiratory distress syndrome connected to mechanical ventilators were studied. INTERVENTIONS: A small polyethylene catheter was threaded through each endotracheal tube such that it could be positioned to measure pressures proximal and distal to the tubes. MEASUREMENTS AND MAIN RESULTS: During SIMV, a significant pressure gradient exists across endotracheal tubes. In addition, although initiation of PC-IRV did lead to a lower peak airway pressure measured proximally, intratracheal peak airway pressure was unchanged. CONCLUSIONS: A pressure gradient exists during inspiration from the ventilator to the trachea in mechanically ventilated patients. Tracheal pressures cannot be predicted from proximal airway pressure monitors because of marked variation in endotracheal tube resistance in vivo. Initiation of PC-IRV does not result in a decrease in peak airway pressure when measured intratracheally.

Adult↗

Variation of nitric oxide concentration during inspiration.

OBJECTIVE: To evaluate the pattern of inspiratory nitric oxide concentration in a simple, constant flow delivery system during the use of two phasic-flow ventilatory modes. DESIGN: Laboratory study in a lung model. SETTING: University experimental laboratory. SUBJECT: Nitric oxide (800 ppm in nitrogen) was administered continuously into the inspiratory circuit to deliver a nitric oxide concentration of 10 and 40 ppm to a test lung during volume-controlled (constant flow) and pressure-controlled (decelerating flow) ventilation, with an FIO2 of 1.0. INTERVENTIONS: In each mode, minute ventilation of 7, 14, and 21 L/min and installation of mixing chambers (none, 1-L, 2-L, and 3.2-L turbulence boxes) were studied, respectively. Nitric oxide and nitric dioxide were monitored by chemiluminescence. Since the nitric oxide/nitrogen gas is the only nitrogen source in the system during ventilation with an FIO2 of 1.0, we evaluated the fluctuation in the inspiratory nitric oxide (NOx) concentration by measuring nitrogen with a fast-response analyzer. To test the effect of the measurement site, we measured nitric oxide concentrations using chemiluminescence at different positions in the inspiratory and expiratory limbs, with and without the mixing chambers, with a minute ventilation of 14 L/min and a nitric oxide concentration of 40 ppm. MEASUREMENTS AND MAIN RESULTS: Nitrogen dioxide production was not influenced by the flow pattern. During a nitric oxide concentration of 10 ppm, nitrogen dioxide was always < 0.6 ppm. During a nitric oxide concentration of 40 ppm, the highest nitrogen dioxide (4.47 ppm) concentration was found at the lowest minute ventilation and the largest inspiratory circuit volume. Nitric oxide values displayed by chemiluminescence indicated stable concentrations at all settings. However, without mixing chambers, NOx concentration calculated from nitrogen measurements demonstrated marked inspiratory fluctuations and was highest with a minute ventilation of 21 L/min and higher during pressure-controlled ventilation compared with volume-controlled ventilation (nitric oxide concentration of 40 ppm, pressure-controlled ventilation: 14.5 to 130.5 ppm; volume-controlled ventilation: 21.6 to 104.7 ppm; nitric oxide concentration of 10 ppm, pressure-controlled ventilation: 3.2 to 30.9 ppm; volume-controlled ventilation: 4.5 to 27.1 ppm). NOx concentration fluctuation decreased with an increasing mixing chamber, and was negligible at all settings with the 3.2-L turbulence box. Nitric oxide concentration fluctuation influenced chemiluminescence measurements. The displayed nitric oxide values varied, depending on the sampling site, and did not accurately reflect mean inspiratory nitric oxide concentration. Incorporation of a mixing chamber eradicated this sampling site influence. CONCLUSIONS: Continuous flow delivery of nitric oxide into the circuit of a phasic-flow ventilator results in marked inspiratory nitric oxide concentration fluctuation that is not detected by a slow-response chemiluminescence analyzer. Moreover, nitric oxide concentration fluctuation can influence the accuracy of the chemiluminescence measurements. These effects can be diminished by using additional mixing chambers to facilitate a stable gas concentration. As these mixing volumes increase the contact time of nitric oxide with oxygen, an increase of nitrogen dioxide has to be taken into account.

Lung↗

Basic determinants of epicardial transudation.

Myocardial edema formation, which has been shown to compromise cardiac function, and increased epicardial transudation (pericardial effusion) have been shown to occur after elevation of myocardial venous and lymphatic outflow pressures. The purposes of this study were to estimate the hydraulic conductance and osmotic reflection coefficient for the epicardium and to determine the effect of coronary sinus hypertension and cardiac lymphatic obstruction on epicardial fluid flux (JV,e/Ae). A Plexiglas hemispheric capsule was attached to the left ventricular epicardial surface of anesthetized dogs. JV,e/Ae was determined over 30-min periods for three intracapsular pressures (-5, -15, and -25 mmHg) and two intracapsular solutions exerting colloid osmotic pressures of 7.0 and 2.0 mmHg. Hydraulic conductance was estimated to be 3.7 +/- 0.5 microliters.h-1.cm-2.mmHg-1. An osmotic reflection coefficient of 0.9 was calculated from the difference in JV,e/Ae of 16.5 +/- 8.4 microliters.h-1.cm-2 between the two solutions. Graded coronary sinus hypertension induced a linear increase in JV,e/Ae, which was significantly greater in dogs without cardiac lymphatic occlusion than in those with occlusion.

Analysis of Variance↗