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Biomedical subjects

S J Allen

Publications and source records attributed to S J Allen.

At least 109 records · Page 6Linked to original sources
PubMed1995

Myocardial edema, left ventricular function, and pulmonary hypertension.

Left ventricular dysfunction has been reported in both experimentally induced and clinical pulmonary hypertension. However, the mechanism by which pulmonary hypertension causes left ventricular dysfunction is unknown. We hypothesized that acute pulmonary hypertension causes left ventricular myocardial interstitial edema and that it is this edema that causes left ventricular dysfunction. In pulmonary artery-banded or sham-operated dogs, left ventricular diameter (septal-free wall axis) and pressure were measured using sonomicrometry crystals and a micromanometer, respectively. These measurements were used to calculate preload recruitable stroke work (PRSW), an index of contractility, and the rate of active relaxation (tau) to assess systolic and diastolic left ventricular function, respectively. After 3 h of pulmonary arterial hypertension or control, the dogs were killed and the left ventricles were excised to determine wet-to-dry weight ratios. The wet-to-dry weight ratios were significantly higher in the pulmonary artery-banded dogs (3.57 +/- 0.12) than in the sham-operated dogs (3.41 +/- 0.17). PRSW decreased to 56.8 +/- 30.3% of control after 3 h of pulmonary hypertension. tau Slowed significantly from 29.8 +/- 5.8 ms at baseline to 63.6 +/- 30.4 ms after 3 h of pulmonary arterial hypertension. There were no differences in PRSW or tau in the sham-operated dogs. We conclude that pulmonary hypertension causes left ventricular myocardial interstitial edema, which results in both systolic and diastolic left ventricular dysfunction.

Acute Disease↗
PubMed1995

Myocardial edema and compromised left ventricular function attributable to dirofilariasis and cardiopulmonary bypass in dogs.

We investigated the relation between left ventricular dysfunction and myocardial edema in dogs with heartworm (Dirofilaria immitis) infection that were undergoing cardiopulmonary bypass. Dogs with and without D immitis were anesthetized by continuous thiopental infusion and were mechanically ventilated. Sonomicrometry crystals were placed on the long and short axes of the left ventricle, and a Millar pressure transducer was placed in the left ventricular chamber. Pressure-volume loops were digitized and continuously recorded. Dogs with and without D immitis were placed on standard hypothermic cardiopulmonary bypass, with 1 hour of aortic cross-clamp. Wet-to-dry weight ratio corrected for residual blood volume was used to quantitate the volume of myocardial edema. Preload recruitable stroke work was used as a preload-independent index of systolic function. Tau, the isovolumic relaxation time constant, was determined to assess diastolic relaxation. Dogs with D immitis had increased baseline myocardial wet-to-dry weight ratio. After cardiopulmonary bypass, myocardial edema increased in all dogs. Acute edema attributable to cardiopulmonary bypass decreased preload recruitable stroke work in all dogs of both groups, and dogs with D immitis could not be weaned from cardiopulmonary bypass. Myocardial edema increased diastolic relaxation times (tau) in dogs with and without D immitis. We conclude that cardiopulmonary bypass and heartworm infection induce myocardial edema. This edema compromises left ventricular systolic and diastolic function making D immitis an important confounding factor in weaning dogs from cardiopulmonary bypass.

Analysis of Variance↗
PubMed1994

Kinetic analysis of the interaction between the diphosphate of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, ddCTP, AZTTP, and FIAUTP with human DNA polymerases beta and gamma.

The inhibitory effects of the diphosphate of (S)-1-(3-hydroxy-2-phosphonylmethoxy-propyl)cytosine (HPMPCpp) toward human DNA polymerases beta and gamma were studied. The Ki values of HPMPCpp were compared with the Ki values of the triphosphates of 3'-azidothymidine (AZTTP), 2',3'-dideoxycytidine (ddCTP) and 5-iodo-2'-fluoroarabinosyluridine (FIAUTP). The Ki values toward DNA polymerase beta in increasing order were 1.32, 1.43, 140, and 520 microM for ddCTP, FIAUTP, AZTTP and HPMPCpp, respectively. The Ki values toward DNA polymerase gamma in increasing order were 0.034, 0.031, 18.3 and 299 microM for ddCTP, FIAUTP, AZTTP and HPMPCpp, respectively. Therefore, HPMPC would be expected to have less inhibitory effects on DNA repair (DNA polymerase beta) and mitochondrial DNA synthesis (DNA polymerase gamma) than ddC, FIAU or AZT.

Antiviral Agents↗
PubMed1994

Cloning of a non-catalytic form of human trkB and distribution of messenger RNA for trkB in human brain.

A truncated form of the human trkB gene has been cloned and sequenced. This gene is related to the trk family of tyrosine kinases, the products of which act as receptors for the neurotrophins. Of these, brain-derived neurotrophic factor and mammalian neurotrophin-4 are the known ligands for the TrkB receptor. Catalytic and non-catalytic (or truncated) forms of the trkB gene have been cloned for rat and mouse. In this study, using in situ hybridization, we describe the distribution of trkB messenger RNA in fetal and adult human brain.

Amino Acid Sequence↗
PubMed1994

Bedside assessment of intravascular volume status in patients undergoing coronary bypass surgery.

BACKGROUND: Management of intravascular volume is crucial in patients after cardiopulmonary bypass as myocardial dysfunction is common. The purpose of this study was to validate a novel bedside technique for real-time assessment of intravascular volumes. METHODS: Eleven patients undergoing cardiopulmonary bypass were studied. In addition to standard monitors, a fiberoptic thermistor catheter was placed in the descending aorta and central venous injections of 10 ml ice-cold indocyanine green dye were performed. Total blood volume was measured by a standard in vitro technique. Circulating and central blood volume were calculated by using cardiac output, mean transit times, and a newly developed recursive convolution algorithm that models recirculation. Measurements were performed after induction of anesthesia and at 1, 6, and 24 h after surgery. RESULTS: A two-compartment model of the circulation was required for adequate fit of the data. We found a significant correlation between total and circulating blood volumes (r = 0.87). One hour after surgery, central blood volume was decreased by 10% (P < 0.05). At 6 and 24 h after surgery, circulating blood volumes were significantly increased by 29% and 20%, respectively (P < 0.01), although central blood volume was similar to control values. Before surgery stroke volume index correlated with circulating blood volume (r = 0.87) but not with pulmonary capillary wedge and central venous pressures. CONCLUSIONS: This study shows that bedside determinations of intravascular blood volumes are feasible and that these measurements are more indicative of intravascular volume status than are either pulmonary capillary wedge or central venous pressures in the post-cardiopulmonary bypass period. Our data also demonstrate that despite a normal central blood volume both circulating and total blood volume are significantly increased in the immediate post-cardiopulmonary bypass period.

Aged↗
PubMed1994

Tepid sponging to reduce temperature in febrile children in a tropical climate.

The effectiveness of tepid sponging, in addition to antipyretic medication, in the reduction of temperature in febrile children living in a tropical environment, was assessed in a prospective, randomized, open trial. Seventy-five children aged between 6 and 53 months who attended the casualty department of the Children's Hospital, Bangkok, Thailand, with fever (rectal temperature > or = 38.5 degrees C) of presumed viral origin were randomized to received either tepid sponging and oral paracetamol (sponged group) or paracetamol alone (control group). Rectal temperature and the occurrence of crying, irritability, and shivering were recorded over the following 2 hours. A greater and more rapid fall in mean rectal temperature occurred in the sponged group than in the control group. Temperature fell below 38.5 degrees C sooner in children in the sponged group than in control children (P < 0.001). At 60 minutes, 38 (95.0%) of the controls still had a temperature of 38.5 degrees C or greater, compared with only 15 children (42.9%) in the sponged group (P < 1 x 10(-5). Crying was associated with sponging, but shivering and irritability occurred in only one child who was being sponged. It is concluded that tepid sponging, in addition to antipyretic medication, is clearly more effective than antipyretic medication alone in reducing temperature in febrile children living in a tropical climate.

Acetaminophen↗
PubMed1994

Body position does not affect the hemodynamic response to venous air embolism in dogs.

Current therapy for massive venous air embolism (VAE) includes the use of the left lateral recumbent (LLR) position. This recommendation is based on animal studies, conducted 50 yr ago, which looked primarily at survival. Little is known, however, about the concomitant hemodynamic response after VAE in various body positions. The purpose of this study was to investigate the hemodynamic and cardiovascular changes in various body positions after VAE. Twenty-two mechanically ventilated supine mongrel dogs received a venous air infusion of 2.5 mL/kg at a rate of 5 mL/s. One minute after the infusion, 100% oxygen ventilation was commenced and the body position of the dogs was changed to either the LLR (n = 6), the LLR with the head 10 degrees down (LLR-10 degrees; n = 6) or the right lateral recumbent (RLR; n = 5) position. Five dogs were maintained in the supine position (SUP; n = 5). One dog died in every group except in the SUP group, where all the dogs recovered. There were no significant differences among the various body positions in terms of heart rate, mean arterial pressure, pulmonary artery pressure, central venous pressure, left ventricular end-diastolic pressure, or cardiac output. The acute hemodynamic changes occurring during the first 5-15 min after VAE recovered to 80% of control within 60 min. Our data suggest that body repositioning does not influence the cardiovascular response to VAE. Specifically, our data do not support the recommendation of repositioning into the LLR position for the treatment of VAE.

Animals↗
PubMed1994

Tracheal compression caused by traumatic thoracic duct leak.

A man with traumatic thoracic duct injury developed a lymphocele causing upper airway obstruction. Despite drainage of the chylothorax, tracheal compression persisted due to a thoracic duct tear. Operative repair of the tear resulted in resolution of the airway obstruction.

Accidents, Traffic↗
PubMed1994

Hyaluronan in cerebrospinal fluid after head injury.

Hyaluronan (HYA) is a large molecular weight polysaccharide which functions in various roles throughout the body. Little is known regarding HYA in human cerebrospinal fluid (CSF). We measured CSF and serum HYA concentrations in eleven patients with varying degrees of head injury. In these patients, CSF HYA ranged from 46 to 772 micrograms/l and serum HYA from 16 to 573 micrograms/l. We did not find any relationship between HYA values in CSF or serum and underlying disease or Glasgow Coma Scale (GCS). The role of CSF HYA in the injured human brain has yet to be elucidated.

Adolescent↗
PubMed1993

Isolation and characterization of cells infiltrating the spinal cord during the course of chronic relapsing experimental allergic encephalomyelitis in the Biozzi AB/H mouse.

A novel method for the isolation of leukocytes from the spinal cords of mice during chronic relapsing experimental allergic encephalomyelitis (CREAE) was developed using discontinuous density gradients. Immunostaining of these cells, together with spinal cord sections and peripheral blood leukocytes, with a panel of monoclonal antibodies enabled a detailed profile of the kinetics and cell phenotype during CREAE to be developed. Overall, the kinetics of cell accumulation within the spinal cord correlated with disease severity. The number of cells increased from an average of 5 x 10(4) in unimmunized animals to 40 x 10(4) in paralysed animals during the initial disease episode. The cell numbers rapidly declined with clinical remission (6 x 10(4) cells/cord) and again dramatically increased during clinical relapse. Low numbers of CD3+ lymphocytes (50-150 cells) were consistently isolated from normal mice. However, the number of T cells infiltrating the spinal cord increased following immunization. The numbers of T cells, macrophages, B cells, neutrophils, and Ig-bearing cells all paralleled the clinical disease course, with T cells and macrophages (showing evidence of myelin breakdown) predominating. T cells infiltrating the spinal cord generally failed to express gamma delta T cell receptors and expressed low levels of IL-2 receptors (5% of infiltrating T cells). These cells were phenotypically dissimilar to peripheral blood leukocytes isolated in parallel, with the spinal cord having a consistently higher ratio (9:1) of CD4+ to CD8+ than the peripheral blood (7:3). The low expression of MEL-14 (L-selectin) and 16a antigen (CD45RBhigh) and the higher levels of Pgp-1 (CD44) expressed by the infiltrating T cells, compared with splenocytes, suggest a preferential recruitment/retention of distinct T cell subsets, possibly memory/primed cells, into the central nervous system from the periphery during neuroimmunological disease.

Animals↗
PubMed1993

Control of immune-mediated disease of the central nervous system with monoclonal (CD4-specific) antibodies.

Chronic relapsing experimental allergic encephalomyelitis (CREAE) was induced in Biozzi AB/H (H-2dq1) mice by active sensitization with spinal cord antigens. A single i.p. injection of CD8-depleting (YTS169.4) monoclonal antibody (mAb) failed to affect the clinical course of CREAE when administered prior to and during the onset of both the initial clinical and subsequent relapse phase of the disease. By contrast similar treatment with both CD4-depleting (YTS191.1) or CD4-blocking/non-depleting (YTS177.9) mAb significantly inhibited disease progression. Treatment shortly before the anticipated onset of clinical EAE prevented the subsequent development of disease, although disease could be provoked following antigen-rechallenge. In contrast, treatment with these antibodies during post-acute remission phase mainly served to delay the incidence of relapse. This suggests that, unless tolerance can be re-induced, treatment of ongoing neuroimmunological disease will require 'pulse' therapy and thus potentiate the problems of long-term immunosuppresion. Despite the findings that CD4-specific antibodies can rapidly reverse overt clinical disease shortly after the onset of disease exacerbation, once neurological dysfunction becomes established anti-CD4 treatment fails to improve the animals clinically, possibly due to the inability to rapidly reverse established demyelination. Although this study does not exclude the potential central action of the injected mAb, the failure to significantly dissociate therapeutic benefit between mAb administered directly into the CNS and that given systemically suggests that a major action of these agents is probably by selectively removing T cells in the peripheral T cell pool.

Animals↗
PubMed1993

Decline in meningococcal antibody levels in African children 5 years after vaccination and the lack of an effect of booster immunization.

Antibodies to group A meningococcal polysaccharide were measured by hemagglutination (HA) and by ELISA in sera obtained from Gambian children before vaccination and 3 weeks, 2 years, and 5 years after vaccination with a group A + group C meningococcal capsular polysaccharide vaccine. Children were 1-4 years old at the time of vaccination. Most showed a good initial response to vaccination, including those aged 1-2 years. However, antibody titers declined progressively during follow-up, and 5 years after vaccination, antibody titers measured by both HA and ELISA had returned to prevaccination levels. This decline was not influenced significantly by a booster dose of vaccine given 2 years after initial immunization. Administration of malaria chemoprophylaxis reduced the rate at which antibody levels fell after initial immunization. Sustained protection of children against group A meningococcal disease will require the development of vaccines that are immunogenic in infants and that can induce T cell memory.

Antibodies, Bacterial↗
PubMed1993

Soluble plasma IL-2 receptors and malaria.

Plasma levels of soluble IL-2 receptor (sIL-2R) were measured by immunoassay in 180 individuals, aged 1-70 years, living in a malaria-endemic community in West Africa. sIL-2R levels were compared with age, malaria parasitaemia, malaria-associated morbidity and cellular immune responses to Plasmodium falciparum antigens. Plasma levels of sIL-2R were independently associated with both age and patent malaria parasitaemia. No significant association was observed between IL-2R levels and concurrent malaria morbidity (i.e. fever associated with malaria), but the number of individuals with clinical malaria at the time of sampling was small. Although there was no association between plasma sIL-2R levels and in vitro proliferative responses of peripheral blood mononuclear cells (PBMC) to a number of defined malaria antigens, we did find a significant negative association between sIL-2R and in vitro proliferation of unstimulated PBMC. High levels of sIL-2R (up to 5500 U/ml) were detected in the plasma of malaria-infected individuals; this is indicative of a vigorous cellular immune response to malaria antigens in vivo and does not support the notion that malaria infections are generally immunosuppressive. Indeed, we found that, at the low levels of parasitaemia present in study subjects, there was no significant difference in the mean proliferative response to malaria antigens in infected subjects when compared with uninfected subjects.

Adolescent↗
PubMed1993

Immunoglobulin M and G antibody responses to Plasmodium falciparum glutamate-rich protein: correlation with clinical immunity in Gambian children.

The aims of the present study were to describe the age-related immunoglobulin M (IgM) and IgG response to part of a 220-kDa glutamate-rich protein (GLURP) from Plasmodium falciparum and to determine possible correlations of possession of these antibodies with malaria morbidity. IgM and IgG levels were measured with a recombinant fusion protein consisting of the carboxy-terminal 783 amino acids of the GLURP. Samples for the study were obtained during a longitudinal malaria morbidity survey performed in The Gambia; cross-sectional surveys were performed at the beginning of the transmission season in May and in October. Seropositivity rates increased with age to a maximum of 77% for IgM and 95% for IgG in adults. High prevalences of seropositivity were associated with certain human leukocyte antigen class II alleles (DRw8, DR9, DR7, DR4, DQw7, and DQw2) or haplotypes. The relationship between anti-GLURP489-1271 antibodies and clinical immunity is not clear; asymptomatically infected children aged 5 to 8 years had significantly higher levels of IgG than clinically ill children of the same age, suggesting that antibodies to the carboxy-terminal part of the GLURP may contribute to immunity to P. falciparum. However, this was not significant for younger children.

Adolescent↗
PubMed1993

Continuous venous air embolism in patients receiving positive end-expiratory pressure.

The occurrence of venous air embolism in critically ill patients can cause profound cardiopulmonary compromise. Recognized causes include aspiration through an indwelling catheter and pneumothorax. We report three patients in whom we found continuous air embolism in the inferior vena cava that persisted for days. The bubbles appeared to arise from splanchnic veins, and they were associated with barotrauma and positive airway pressure. In the two survivors, the bubbling ceased when the ARDS resolved and airway pressures were decreased. We suspect that venous air embolism is not an uncommon occurrence in critically ill patients receiving high positive airway pressure.

Adolescent↗