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Biomedical subjects

M J Gardner

Publications and source records attributed to M J Gardner.

At least 55 records · Page 3Linked to original sources
PubMed1998

The continuing problem of all-terrain vehicle injuries in children.

BACKGROUND: After the introduction of the all-terrain vehicle (ATV) in the United States in 1971, deaths and injuries in both adults and children rose dramatically. In 1988, the Consumer's Product Safety Commission (CPSC) and all manufacturers of ATVs signed legally binding "Consent Decrees," designed to decrease the number of ATV-related deaths and injuries, especially in children. METHODS: This report reviews retrospectively the mechanism of injury as well as the injuries in 51 children caused by ATV crashes during a 5-year period after the signing of the decrees. RESULTS: Data included age; sex; type of ATV (three or four wheel); position of the patient on the vehicle (driver or passenger); helmet usage; and mechanism of vehicular accident, including collision with a stationary or moving object, rollover, or fall from the vehicle. Mechanism data indicate loss of control of vehicle or fall from the vehicle as the most common cause of injury. Injury statistics included body regions and parts injured, injury severity score (ISS), and complications or disabilities resulting from injury. Mean ISS was 13.6 +/- 9.7 (range, 1 to 50). Eighteen patients (35%) had ISSs greater than 15. Helmets were worn by only 30% of patients. There were two deaths, and two patients suffered permanent paralysis. Orthopedic injuries were the most common injury and were of adult type with 61% classified as open or comminuted. CONCLUSIONS: The magnitude and severity of these injuries argue that this recreational vehicle is exceedingly dangerous for children. The consent decrees have had little effect on reducing the injuries in children from ATVs and should be reevaluated.

Accidents↗
PubMed1998

Sequencing the genome of Plasmodium falciparum.

Advances in microbial genomic sequencing have the potential to revolutionize the control of infectious diseases. Recently, a consortium of researchers and funding agencies from the United States and Great Britain have embarked on a project to sequence the genome from Plasmodium falciparum, the most important cause of human malaria. The Malaria Genome Sequencing Project has reached an important milestone with the completion of the entire DNA sequence and annotation of chromosome 2, a 950 kilobase chromosome of Plasmodium falciparum. This review article will provide an overview of the malaria genome sequencing project, highlight progress in the field of microbial sequencing, and suggest new directions for future malaria research.

Journal Article↗
PubMed1998

Protection of mice against Plasmodium yoelii sporozoite challenge with P. yoelii merozoite surface protein 1 DNA vaccines.

Immunization of mice with DNA vaccines encoding the full-length form and C and N termini of Plasmodium yoelii merozoite surface protein 1 provided partial protection against sporozoite challenge and resulted in boosting of antibody titers after challenge. In C57BL/6 mice, two DNA vaccines provided protection comparable to that of recombinant protein consisting of the C terminus in Freund's adjuvant.

Animals↗
PubMed1998

Simultaneous induction of multiple antigen-specific cytotoxic T lymphocytes in nonhuman primates by immunization with a mixture of four Plasmodium falciparum DNA plasmids.

CD8(+) T cells have been implicated as critical effector cells in protective immunity against malaria parasites developing within hepatocytes. A vaccine that protects against malaria by inducing CD8(+) T cells will probably have to include multiple epitopes on the same protein or different proteins, because of parasite polymorphism and genetic restriction of T-cell responses. To determine if CD8(+) T-cell responses against multiple P. falciparum proteins can be induced in primates by immunization with plasmid DNA, rhesus monkeys were immunized intramuscularly with a mixture of DNA plasmids encoding four P. falciparum proteins or with individual plasmids. All six monkeys immunized with PfCSP DNA, seven of nine immunized with PfSSP2 DNA, and five of six immunized with PfExp-1 or PfLSA-1 DNA had detectable antigen-specific cytotoxic T lymphocytes (CTL) after in vitro restimulation of peripheral blood mononuclear cells. CTL activity was genetically restricted and dependent on CD8(+) T cells. By providing the first evidence for primates that immunization with a mixture of DNA plasmids induces CD8(+) T-cell responses against all the components of the mixture, these studies provide the foundation for multigene immunization of humans.

Amino Acid Sequence↗
PubMed1998

In vitro expression and in vivo immunogenicity of Plasmodium falciparum pre-erythrocytic stage DNA vaccines.

DNA vaccine plasmids were constructed that encoded four pre-erythrocytic antigens from the human malaria parasite Plasmodium falciparum: circumsporozoite protein (PfCSP); sporozoite surface protein 2 (PfSSP2); carboxyl terminus of liver stage antigen 1 (PfLSA-1 c-term); and, exported protein 1 (PfExp-1). Antigen expression was evaluated in vitro by immunoblot analysis of tissue culture cells following transient transfection with each plasmid. Clearly detectable levels of expression depended upon, or were markedly enhanced by, fusion of the antigen encoding sequences in-frame with the initiation complex and peptide leader sequence of human tissue plasminogen activator protein. Mice injected with these plasmids produced antigen specific antibody and cytotoxic T lymphocyte responses. However, the magnitudes of the responses were not always predicted by the in vitro expression assay. The results of this study provided the basis for further testing of these plasmids in primates and the formulation of multi-component pre-erythrocytic DNA vaccines for efficacy testing in human volunteers.

Amino Acid Sequence↗
PubMed1997

Definition of predicted effective antiarrhythmic drug therapy for ventricular tachyarrhythmias by the electrophysiologic study approach: randomized comparison of patient response criteria.

OBJECTIVES: We sought to compare efficacies of therapy for ventricular tachyarrhythmias selected by programmed stimulation using two different patient response efficacy criteria: <5 versus <16 repetitive ventricular responses. BACKGROUND: Therapy selection for ventricular tachyarrhythmias by programmed stimulation requires definition of a patient response that predicts long-term efficacy. Such definitions have not been previously compared prospectively. METHODS: Patients with sustained ventricular tachyarrhythmias were randomized to therapy selection using either the <5 or <16 repetitive response criterion of predicted effective therapy. The primary end point was sudden death or recurrence of ventricular tachyarrhythmia requiring intervention. RESULTS: Predicted effective drug therapy was found for 23 (34%) of 68 patients randomized to the <5 criterion and 29 (36%) of 81 patients randomized to the <16 criterion (p = NS). Definition of therapy required 3.0 +/- 1.6 drug trials (mean +/- SD) in patients randomized to the <5 criterion and 2.9 +/- 1.8 trials in patients randomized to the <16 criterion (p = NS). Patients randomized to the <5 criterion had a lower 2-year probability of the primary end point (0.20 +/- 0.05) than did patients randomized to the <16 criterion (0.33 +/- 0.05, one-tailed p = 0.004). The advantage of the <5 criterion was also seen in subgroup analyses involving patients with and without an initial drug efficacy prediction. CONCLUSIONS: The programmed stimulation approach to the selection of antiarrhythmic therapy for ventricular tachyarrhythmias using a patient response criterion of <5 repetitive ventricular responses results in a lower probability of recurrence of ventricular tachyarrhythmia than does use of a <16 repetitive response criterion.

Actuarial Analysis↗
PubMed1997

Computed tomography grade of splenic injury is predictive of the time required for radiographic healing.

It is largely unknown when a child who has suffered a splenic laceration can return to full unrestricted activity. The purpose of this prospective study is to establish whether the grade of splenic injury is predictive of the length of time required for radiographic healing, and to determine whether there are any adverse long-term sequelae after resumption of unlimited activity. Sixty-nine patients underwent successful nonoperative management (NOM) of computed tomography (CT)-documented splenic injury over a 4-year period. Fifty-eight patients completed follow-up. Mean age was 9.8 years (range, 1 to 17) and mean injury severity score (ISS) was 14.4 (range, 4 to 38). Mechanisms of injury were motor vehicle accident (n = 11), motor vehicle pedestrian (n = 5), falls (n = 13), bike crashes (n = 12), sports (n = 8), all-terrain vehicle (n = 4), and horse (n = 5). The CT-documented injury was identified by discharge ultrasound scan (US) in all cases. There were no long-term complications. Mean time to US healing in grade I (n = 9), II (n = 26), III (n = 19), IV (n = 4) injuries was 3.1, 8.2, 12.1, and 20.7 weeks, respectively. P values were significant (P < .01) in all cases when compared with the next lower injury grade. The time to radiographic healing is directly proportional to the severity of the splenic injury. There was excellent correlation between the initial CT scan and identification of the injury on the discharge US. No long-term complications leg, delayed splenic rupture, splenic pseudocyst) were seen in this study. Pediatric patients who have suffered splenic injury can safely return to full unrestricted activity when the US documents healing.

Adolescent↗
PubMed1997

Binding of ovarian cancer cells to immobilized hyaluronic acid.

Ovarian cancer has the highest mortality rate of any gynaecological malignancy. This is caused by metastatic deposits obstructing the intestinal tract. Very little is known about the molecules involved in the initial attachment of the metastatic tumour cells to the peritoneal mesothelial lining. Previously, we showed that many ovarian tumour lines express the adhesion molecule, CD44, on their cell surface. The major ligand for CD44 is the extracellular matrix glycosaminoglycan, hyaluronic acid (HA). Because mesothelial cells have a pericellular cost that contains large amounts of HA, it was postulated that the CD44/HA interaction is an important stage in ovarian cancer spread. However, it was difficult to demonstrate this interaction in an in vitro adhesion assay with mesothelial cells as most of the HA, and presumably the bound tumour cells, were lost from the mesothelial cells during the washing steps of the assay. In order to try and clarify the situation, the adhesion of six ovarian tumour lines to immobilized HA was measured. Four lines expressed high levels of CD44 and two lines expressed negligible amounts. Preliminary experiments were carried out with one of the CD44-expressing lines. After coating a plate overnight with 3 mg ml(-1) HA, the 5 min adhesion of this line varied between 2% and 73% according to the type of plate that was used. Falcon Micro Test III flexible plates gave the highest adhesion and was used for further experiments. Plates were coated with concentrations of HA between 0.001 mg ml(-1) and 3 mg ml(-1). All CD44 expressing lines adhered to HA, but the maximum adhesion and the adhesion strength varied with the line studied and was not closely related to the total CD44 expression. These results suggest that CD44 on ovarian tumour cells binds to HA on mesothelial cells. As much of the HA can be very easily lost from the mesothelial cell surface, additional factors such as the strength of the CD44/HA interaction, and the formation of bonds by the tumour cells with other membrane adhesion molecules, such as integrins, are also important in promoting tumour spread.

Antigens, CD↗
PubMed1997

Binding of ovarian cancer cells to immobilized hyaluronic acid.

Ovarian cancer has the highest mortality rate of any gynaecological malignancy. This is caused by metastatic deposits obstructing the intestinal tract. Very little is known about the molecules involved in the initial attachment of the metastatic tumour cells to the peritoneal mesothelial lining. Previously, we showed that many ovarian tumour lines express the adhesion molecule, CD44, on their cell surface. The major ligand for CD44 is the extracellular matrix glycosaminoglycan, hyaluronic acid (HA). Because mesothelial cells have a pericellular cost that contains large amounts of HA, it was postulated that the CD44/HA interaction is an important stage in ovarian cancer spread. However, it was difficult to demonstrate this interaction in an in vitro adhesion assay with mesothelial cells as most of the HA, and presumably the bound tumour cells, were lost from the mesothelial cells during the washing steps of the assay. In order to try and clarify the situation, the adhesion of six ovarian tumour lines to immobilized HA was measured. Four lines expressed high levels of CD44 and two lines expressed negligible amounts. Preliminary experiments were carried out with one of the CD44-expressing lines. After coating a plate overnight with 3 mg ml(-1) HA, the 5 min adhesion of this line varied between 2% and 73% according to the type of plate that was used. Falcon Micro Test III flexible plates gave the highest adhesion and was used for further experiments. Plates were coated with concentrations of HA between 0.001 mg ml(-1) and 3 mg ml(-1). All CD44 expressing lines adhered to HA, but the maximum adhesion and the adhesion strength varied with the line studied and was not closely related to the total CD44 expression. These results suggest that CD44 on ovarian tumour cells binds to HA on mesothelial cells. As much of the HA can be very easily lost from the mesothelial cell surface, additional factors such as the strength of the CD44/HA interaction, and the formation of bonds by the tumour cells with other membrane adhesion molecules, such as integrins, are also important in promoting tumour spread.

Cell Adhesion↗
PubMed1997

Single rope tree swing injuries among children.

OBJECTIVE: To examine the scope and severity of injuries sustained from falls from single rope tree swings among children. METHODS: Twenty-six children formed the basis of this retrospective study. Patients were divided into three groups based on the estimated distance of their fall (one, two, or three stories). Data were analyzed with respect to mechanism of injury, age, gender, length of hospital stay, injury severity score, number and type of injuries, and mortality. RESULTS: Eighteen patients fell from ropes, and 8 from vines (all onto packed dirt). Fourteen falls occurred from one story or less, 8 from two stories, and 4 from three stories. One death occurred from intracranial injury following a two-story fall. No difference in age, gender, injury severity score, or length of hospital stay with respect to the height of the fall was observed. Falls from lower heights resulted in equally severe injuries as falls from higher heights. Overall, head trauma was the most common injury (58%) followed by long bone fractures (42%), axial skeletal fractures (23%), and intra-abdominal visceral injuries (8%). CONCLUSIONS: The present study demonstrated that recreational single rope tree swing injuries among children resulted in significant morbidity regardless of the height of the fall. This activity carries a substantial risk for serious injury. The mechanism of injury, clinical data, and the importance of medical awareness and patient education are emphasized.

Abdominal Injuries↗
PubMed1997

Effect of sertraline on the pharmacokinetics and protein binding of diazepam in healthy volunteers.

A double-blind randomised placebo-controlled study was conducted in healthy male volunteers to determine the effects of sertraline on the pharmacokinetics of diazepam and its primary metabolite, N-demethyldiazepam. The effect of sertraline on the plasma protein binding of diazepam was also studied. Sertraline 50 mg/day titrated over a 10-day period to 200 mg/day or placebo was administered for 32 days. A single intravenous dose of diazepam 10 mg was given before the start, and after 21 days of sertraline or placebo treatment. The pharmacokinetic analyses were based on data from 20 individuals. The systemic clearance of diazepam decreased by 32% (-0.100 ml/min/kg) in the sertraline group compared with a 19% decrease (-0.054 ml/min/kg) in the placebo group (p = 0.0266). However, this small difference (13%) between the 2 groups was not considered meaningful. Other than a prolonged time to maximum plasma concentration for N-demethyldiazepam, no other pharmacokinetic parameters were significantly altered by sertraline. The plasma protein binding of diazepam was unchanged by concomitant administration of sertraline. These results suggest that sertraline at the maximum recommended dosage under steady-state conditions, and demethylsertraline, the principal metabolite of sertraline, are unlikely to exert significant inhibitory effects on the CYP2C19 and CYP3A3/4 hepatic isoenzymes responsible for the metabolism of diazepam. Therefore, it would be expected that sertraline would, similarly, have a minimal effect on the pharmacokinetic profile of other drugs metabolised by these hepatic isoenzymes.

1-Naphthylamine↗
PubMed1996

The mitogenic response to EGF of rat hepatocytes cultured on laminin-rich gels (EHS) is blocked downstream of receptor tyrosine-phosphorylation.

Hepatocytes cultured on type I collagen proliferate in response to mitogenic growth factors yet de-differentiate. By contrast, hepatocytes on laminin-rich gels (EHS) demonstrate stable differentiated functions, while DNA synthesis is negligible. Here we have confirmed that this lack of proliferation was not due to deterioration of the cells because albumin release was maintained for several weeks. Additionally it does not appear to be due to the presence of the growth inhibitor TGF beta within the gel since and anti-TGF beta antibodies did not reverse the growth blockade. The addition of EGF to cells cultured on either type I collagen or EHS gel induced increased tyrosine phosphorylation of a 180kDa protein which ran in a position identical to that of the EGF receptor detected by a specific EGF receptor antibody. We conclude that since functional EGF receptors were present, the mitogenic response of hepatocytes on EHS gels is blocked at some downstream signaling event beyond that of receptor tyrosine autophosphorylation.

Animals↗
PubMed1996

Human ovarian tumour cells can bind hyaluronic acid via membrane CD44: a possible step in peritoneal metastasis.

Our previous studies have suggested that the interaction between hyaluronic acid (HA) on peritoneal mesothelial cells and the membrane adhesion molecule, CD44, on ovarian tumour cells could be important in ovarian cancer metastasis. In order to study this further, adhesion of six ovarian tumour lines to HA coated on to a plastic surface was investigated. Four lines bound to the HA coat and two lines did not. The adhesive lines were those that expressed high amounts of CD44, but the degree of adhesion was not closely correlated with CD44 expression. The results suggested that different tumour lines had different affinities for HA. Treatment of the HA coat with hyaluronidase substantially reduced adhesion. Adhesion was also partially reduced if the tumour cells were preincubated with either soluble HA, or anti-CD44 antibodies directed against the HA binding region. An antibody against a non-HA binding region only slightly blocked adhesion at high antibody concentrations. Only the CD44H isoform was detected by immunoprecipitation on the tumour cells. These results suggest that ovarian tumour cells can attach to immobilised HA via CD44H on the cell membrane.

Antibodies↗
PubMed1996

Accuracy of determination of trace metals in soil and sewage sludge.

Errors in the analysis of liquid samples are often large enough to be important. For solid materials, additional potential complications arise in separating the determinand from the sample matrix and in controlling possible interferences from co-extracted species. These considerations have led to the development of a stepwise, co-ordinated approach by which a group of laboratories have achieved predefined standards of accuracy. Sample digestion has been examined. The analysis of digests has then been addressed; the control of analytical precision has been emphasised. Finally, a demonstration of overall comparability has been undertaken. The results are presented.

Journal Article↗
PubMed1996

Determination of chromium(III) and total chromium in marine waters.

The development of an analytical technique is described which may be used to determine chromium, chromium(III) and chromium(VI) in estuarine and coastal waters. The method is based on selective micro-solvent extraction with subsequent GFAAS. The technique has been applied in a major North Sea estuary. The results obtained confirm that thermodynamic factors alone cannot be relied upon to describe the form of chromium in estuaries. Kinetic factors appear to have a strong influence over speciation and lead to the persistence of Cr(III) species in environments where Cr(VI) would be expected to be present.

Journal Article↗
PubMed1996

Body surface potential mapping of a patient with Wolff-Parkinson-White syndrome with two accessory pathways and two atrial pacemaker complexes.

As part of an ongoing research protocol, a patient with Wolff-Parkinson-White syndrome underwent body surface potential mapping and electrophysiologic studies before radiofrequency ablation therapy. Careful analysis of the body surface potential mapping data made it possible to distinguish four different map sequences representing four different cardiac complexes. Analysis of these maps is consistent with two accessory pathways, with the additional pathology of two distinct atrial pacemaker sites. A right anterosuperior pathway was found to conduct continuously. The second pathway is consistent with a right inferior pathway conducting intermittently. The analysis demonstrates the type of information that can be extracted from body surface potential maps, even in the presence of complex pathologies.

Adult↗
PubMed1996

Hemodynamic significance of pediatric femur fractures.

PURPOSE: To determine whether hemodynamically significant bleeding occurs after pediatric femur fractures. METHOD: A retrospective chart review was performed; demographic and injury data were collected for all patients with the diagnosis of femur fracture over a 30-month period at a level/ pediatric trauma center. Included were patients with multisystem injury and patients with femur fractures as the only injury. The incidence of hemodynamic insufficiency, the reasons for and timing of transfusions, and the changes in hematocrit levels over time were evaluated. RESULTS: One hundred seventy-eight children were identified (182 femur fractures). There were 116 boys and 62 girls, and the mean age was 6.04 +/- 4.5 years (range, 1 month to 19 years). The mechanisms of injury included falls (46), pedestrian/ motor vehicle accidents (43), motor vehicle crashes (19), sports accidents (22), abuse (10), and miscellaneous (38). The mean Injury Severity Score (ISS) was 5.88 +/- 3.93 (range, 4 to 29). There were no deaths. The length of hospital stay was 8.13 +/- 9.37 days (range, 1 to 43 days). Prehospital treatment included early immobilization. Fracture treatment was according to recognized orthopedic techniques based on age, size, and fracture configuration. The mean hematocrit in the emergency department was 34% +/- 3.5% (range, 27.8% to 44.4%) and 32% +/- 6.6% (range, 16.9% to 47.8%) at 24 hours. 67 patients (38%) suffered multiple injuries. Mean ISS for this group was 9.4 +/- 5.0 (range, 5 to 29). Four patients had hemodynamic insufficiency at the time of admission. All were in the multiple-injury group Seven of these 67 patients (10%) required transfusion-three in the first 24 hours (two in the emergency department [associated with severe facial/scalp bleeding] and one in the operating room [associated with severe liver injury]) and four after the first 24 hours (three associated with intraoperative orthopedic procedures and one with a hemothorax). The mean age of those who underwent transfusion was 8.29 +/- 4.79 years, and their mean ISS was 13.71 +/- 4.61. All patients who required transfusion had been injured in motor vehicle crashes or in pedestrian/motor vehicle accidents. One hundred eleven children had isolated closed femur fractures. No patient in this group had evidence of hemodynamic insufficiency or required transfusion. The initial mean hematocrit was 34.5% +/- 2.7%, and the mean 24-hour hematocrit was 34.6% +/- 3.2%. We found that (1) no child with an isolated closed femur fracture had evidence of hemodynamic instability, or showed significant blood loss as evidenced by a decreasing hematocrit at 24 hours, and (2) in this series, evidence of hemodynamic insufficiency and/or the need for transfusion was found only in multiply injured children. CONCLUSION: Hemodynamic instability or evidence of a declining hematocrit in the child should not be attributed to a closed femur fracture and that other sources of blood loss must be found.

Anemia↗