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Biomedical subjects

G Barker

Publications and source records attributed to G Barker.

At least 37 records · Page 2Linked to original sources
PubMed2000

[Preliminary report: use of clinical criteria for the determination of pediatric brain death and confirmation by radionuclide cerebral blood flow].

The medical records of all brain dead patients (n = 228) at the Hospital for Sick Children, Toronto from January 1990 to December 1999 were reviewed. A radionuclide cerebral blood flow study (RCBFS) as a supportive and confirmatory test was performed on 27 patients and the clinical diagnosis of brain death was confirmed on all of them. A RCBFS was performed on 10 out of 27 patients because full clinical evaluation could not be performed due to severe facial injuries or cervical injuries. A RCBFS was performed on 17 patients who underwent a full clinical evaluation, of which 15 cases were due to uncertainty in the clinical etiology of the deep coma and 2 cases were due purely to the need to persuade the family. In recent years, RCBFS was not used as extensively on patients who underwent a full clinical evaluation, reflecting social acceptance and a higher level of clinical certainty in diagnosing brain death in children. This study supports the opinion that brain death can be accurately diagnosed in pediatric patients with clinical criteria alone and confirmatory tests are not necessary in most cases.

Adolescent↗
PubMed1999

The biosynthesis and post-translational modification of Pbs21 an ookinete-surface protein of Plasmodium berghei.

Radiolabelled methionine incorporation into synchronised Plasmodium berghei gametocytes or ookinete cultures, showed that Pbs21 is not synthesised in bloodstage parasites; synthesis was detected within three hours of induction of gametogenesis; synthesis was triggered at gametogenesis, not by fertilisation. We show native Pbs21 to be a hydrophobic membrane protein that was insensitive to cleavage by phosphatidylinositol phospholipase C (PI-PLC), but sensitive to alkaline hydroxylamine, and partially sensitive to glycosylphosphatidylinositol-dependent phospholipase D (GPI-PLD) and HNO2. 3H-myristic and palmitic acid, 3H-glucosamine and mannose incorporation indicated Pbs21 was acylated and glycosylated. Linkage of the acyl group was sensitive to HNO2, which released an acyl-phosphatidylinositol more hydrophobic than that released from P3 of Trypanosoma brucei. All these properties are consistent with the presence of a malaria-specific glycosylphosphatidylinositol (GPI) anchor. In contrast recombinant Pbs21 (rPbs21), expressed in Spodoptera frugiperda cells, was sensitive to both PI-PLC and GPI-PLD, consistent with the protein being modified by a different (S. frugiperda) GPI anchor. Brefeldin A blocked secretion of rPbs21 within a cytoplasmic reticular compartment. Following deletion of the putative GPI anchor addition site (amino acids 189 213), the protein was transported to the cell surface and secreted directly into the aqueous phase of the culture medium. Deletion of amino acids 205-213 disrupted Pbs21 processing, transport through the ER and distribution onto the cell surface. Deletion of amino acids 1-28 prevented transport of Pbs21 into the ER. This suggests that correct processing of the GPI anchor in the ER-Golgi network is essential for the successful secretion of the recombinant protein, which is additionally dependent upon an N-terminal secretory signal sequence.

Acylation↗
PubMed1999

Intragraft expression of transforming growth factor beta1 gene in isolated glomeruli from human renal transplants.

BACKGROUND: Experimental evidence suggests that transforming growth factor (TGF) beta1 is a fibrogenic cytokine. The histopathological changes of chronic renal allograft nephropathy are dominated by fibrotic changes and TGF-beta may have an important aetiological role. This study investigated the relationship between intragraft TGF-beta gene expression and extracellular matrix protein deposition in human renal allografts. METHODS: Sixteen cadaveric renal transplant recipients immunosuppressed with cyclosporin and steroids were studied. Individual glomeruli were isolated from protocol needle-core biopsies and, following messenger RNA extraction, intragraft gene expression was studied by reverse transcriptase-polymerase chain reaction. Collagen III deposition in these renal transplant biopsies was examined by immunohistochemistry and quantified by computerized histomorphometry. RESULTS: There was a positive correlation between renal cortical collagen III immunostaining and the levels of glomerular complementary DNA for TGF-beta1. CONCLUSION: TGF-beta1 is a profibrotic influence in human renal transplants. The methods described should prove of benefit in investigating the mechanisms of chronic renal allograft damage.

Biopsy, Needle↗
PubMed1997

Congenital diaphragmatic hernia--a tale of two cities: the Toronto experience.

PURPOSE: The optimal therapy for congenital diaphragmatic hernia (CDH) is evolving. This study analyzes the results of treatment of CDH in a large tertiary care pediatric center using conventional and high-frequency oscillatory ventilation (HFOV) without extracorporeal membrane oxygenation (ECMO) contrasting these with a parallel study from a similar large urban center using conventional ventilation with ECMO. METHODS: Between 1981 and 1994, 223 consecutive neonates who had CDH diagnosed in the first 12 hours of life were referred for treatment before repair. Conventional ventilation was used with conversion to HFOV for refractory hypoxemia or hypercapnia, and a predicted near 100% mortality rate. ECMO was used in only three patients, all of whom died. A retrospective database was collected. Thirty-one clinical variables were tested for their association with the outcome. Common ventilatory and oxygenation indices were tested for their prognostic capability. RESULTS: Apgar scores, birth weight, right-sided defects, pneumothorax, total ventilatory time, and the use of high frequency oscillatory ventilation were the only variables associated with outcome. A modified ventilatory index and postductal A-aDo2 were strong prognostic indicators. From 1981 to 1984 surgery was performed on an emergency basis. Since 1985 surgery was deferred until stabilization had been achieved. This resulted in a shift in the mortality from postoperative to preoperative with no change in total survival. HFOV did not alter the overall survival. Results of autopsies performed (70%) showed significant pulmonary hypoplasia and barotrauma as the primary causes of death. The survival was 54.7%. CONCLUSION: Conventional ventilation with HFOV produced equal survival to conventional ventilation with ECMO in two comparable series. Pulmonary hypoplasia was the principle cause of death. This continued high mortality at both centers suggests that new therapies are required to improve outcomes.

Extracorporeal Membrane Oxygenation↗
PubMed1997

Cloning and expression of the thrombospondin related adhesive protein gene of Plasmodium berghei.

Sporozoite recognition of host cells is a key step in the life-cycle of malaria parasites. Two sporozoite proteins have so far been characterized in some detail, the circumsporozoite protein (CS) and thrombospondin related adhesive protein (TRAP). We report here the cloning and expression of the TRAP gene homologue from Plasmodium berghei, PbTRAP. The PbTRAP gene encodes a protein of 606 amino acids having a deduced molecular mass of 66 kDa. The overall structure is clearly that of the TRAP family having a signal sequence followed by an integrin A domain, a sulphatide binding motif, followed by a proline based repeat before a transmembrane domain and helical cytoplasmic tail. The observed molecular mass is almost 50% larger than expected, this can be explained almost entirely by the abnormal behaviour in SDS-PAGE of the proline based repeat. As would be expected PbTRAP shows greatest similarity with the P. yoelli TRAP homologue sporozoite surface protein 2 (SSP2) than with PfTRAP, the TRAP gene from P. falciparum. The pattern of expression is similar to that of SSP2.

Amino Acid Sequence↗
PubMed1997

CBFA2, frequently rearranged in leukemia, is not responsible for a familial leukemia syndrome.

We have identified a family with an autosomal dominant platelet disorder with a predisposition for developing myeloid malignancies and have previously demonstrated linkage of this trait to chromosome 21q22.1-22.2. The nearest flanking markers, D21S1265 and D21S167, define the familial platelet disorder (FPD) critical region at a genetic distance of approximately 15.2 centimorgans and physical distance of approximately 6 megabases. This locus is of particular interest as it has previously been implicated in the pathogenesis of acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL) through the (8;21), (3;21) and (12;21) chromosomal translocations. In each of these cases, the CBFA2 gene is rearranged. As well, there is a potential association of this locus with the hematologic abnormalities seen in Down syndrome (trisomy 21). To identify the mutant gene in this pedigree, a positional cloning strategy has been undertaken. Several candidate genes map to this locus including: CBFA2, IFNAR1, IFNAR2, CRFB4, GART, SON, KCNE1, SCL5A3 and ATP50. CBFA2, as well as IFNAR1 and CRFB4, were the focus of initial mutational analysis efforts. In this report, we exclude CBFA2 as a candidate by Northern and Southern blotting, RNase protection, single-strand conformational polymorphism (SSCP), direct sequencing and gel-shift analysis. Exons of the IFNAR1 and CRFB4 genes were also analyzed by SSCP and demonstrated no evidence of mutation. SSCP analysis identified a new polymorphism in the second exon of the CRFB4 gene and confirmed a previously described polymorphism in the fourth exon of IFNAR1. Efforts are currently underway to delimit further the FPD critical region and to analyze the other known candidate genes, as well as novel candidate genes, which map to this locus.

Core Binding Factor Alpha 2 Subunit↗
PubMed1997

Patient-based research in a tertiary pediatric centre: a pilot study of markers of scientific activity and productivity.

OBJECTIVE: To characterize patient-based research in a large academic pediatric centre, to examine measures of research activity and productivity among the 44 clinical programs and to examine whether there is a relation among various measures of scientific productivity. DESIGN: Survey. PARTICIPANTS: Clinical programs. OUTCOME MEASURES: Analysis of all patient-based research projects for the 1993-94 and 1994-95 fiscal years, research funding and cumulative citation impact. RESULTS: Only half of the research projects were funded by extramural grants (peer-reviewed or industrial). There were strong and significant correlations among the 3 markers of scientific activity and productivity: funding, peer-reviewed publications and cumulative citation impact. Only small programs with 3 or fewer faculty members with protected time available to develop research programs achieved a citation impact of 30 or more per full-time equivalent position, with larger programs being "diluted" by clinicians performing little or no research. CONCLUSIONS: In the context of patient-based research, quantity of research correlated with measures of quality. This study highlights the need for clinical departments and medical faculties to consider activity and productivity markers in setting standards for patient-based research.

Hospitals, Pediatric↗
PubMed1996

Outcome of out-of-hospital cardiac or respiratory arrest in children.

BACKGROUND: Among adults who have a cardiac arrest outside the hospital, the survival rate is known to be poor. However, less information is available on out-of-hospital cardiac arrest among children. This study was performed to determine the survival rate among children after out-of-hospital cardiac arrest and to identify predictors of survival. METHODS: We reviewed the records of 101 children (median age, two years) with apnea or no palpable pulse (or both) who presented to the emergency department at the Hospital for Sick Children in Toronto. The characteristics of the patients and the outcomes of illness were analyzed. We assessed the functional outcome of the survivors using the Pediatric Cerebral and Overall Performance Category scores. RESULTS: Overall, there was a return of vital signs in 64 of the 101 patients; 15 survived to discharge from the hospital, and 13 were alive 12 months after discharge. Factors that predicted survival to hospital discharge included a short interval between the arrest and arrival at the hospital, a palpable pulse on presentation, a short duration of resuscitation in the emergency department, and the administration of fewer doses of epinephrine in the emergency department. No patients who required more than two doses of epinephrine or resuscitation for longer than 20 minutes in the emergency department survived to hospital discharge. The survivors who were neurologically normal after arrest had had a respiratory arrest only and were resuscitated within five minutes after arrival in the emergency department. Of the 80 patients who had had a cardiac arrest, only 6 survived to hospital discharge, and all had neurologic sequelae. CONCLUSIONS: These results suggest that out-of-hospital cardiac arrest among children has a very poor prognosis, especially when efforts at resuscitation continue for longer than 20 minutes and require more than two doses of epinephrine.

Adolescent↗
PubMed1996

Intensive care management of paediatric organ donors and its effect on post-transplant organ function.

OBJECTIVES: 1. To document the clinical course of paediatric beating heart organ donors. 2. To evaluate the effect of the ICU management of pediatric donors on the immediate function of transplanted organs. 3. To examine the validity of current donor selection criteria. DESIGN: Retrospective chart review and case series study. SETTING: Multidisciplinary ICU of tertiary referral paediatric hospital. PATIENTS: All patients who became solid organ donors between January 1980 and July 1990. OUTCOME MEASURES: 1. Incidence of major physiological abnormalities of the cardiovascular, pulmonary, renal and metabolic systems. 2. Number of organs retrieved and transplanted, reasons for non-transplantation of donated organs. 3. Immediate post-transplant function of transplanted organs. RESULTS: Seventy-seven organ donors were identified from whom 134 kidneys, 31 livers and 12 hearts were transplanted. Sixty (78%) patients developed diabetes insipidus. Sustained hypotension occurred in 41 (53.2%) and was commoner in patients treated with inotropic agents in the presence of a low central venous pressure and in patients with diabetes insipidus who did not receive anti-diuretic hormone replacement. Twenty-seven patients suffered at least one cardiac arrest. The data on post-transplant function were obtained for 129 kidneys (from 70 donors) 30 livers and 9 hearts. Fifty-two kidneys, 10 livers and 2 hearts were transplanted from donors who had suffered at least one cardiac arrest without apparent adverse effect on post-transplant organ function. Thirty-six kidneys from 31 donors suffered either acute tubular necrosis (ATN) or primary non-function. The donors of these organs spent longer in ICU (60.6 +/- 45.7 h versus 41.8 +/- 30.1 h p = 0.045) and had a higher mean maximum serum sodium concentration (163.4 +/- 10.9 versus 158.5 +/- 9.5 mmol/l p = 0.05) than those without these complications. The serum creatinine concentration and degree of inotropic support did not predict post-transplant function. Standard biochemical tests for hepatic function, the dose of inotropic agent received, time in ICU and incidence of hypotension did not predict post-transplant liver function. CONCLUSIONS: Aggressive fluid resuscitation and management of diabetes insipidus may promote stability in paediatric organ donors. Donor cardiac arrest does not alter the ICU course or compromise post-transplant organ function. The current criteria used for donor selection failed to predict post-transplant organ function and their use may increase organ wastage.

Adolescent↗
PubMed1995

A canine study of cold water drowning in fresh versus salt water.

OBJECTIVE: To compare the pathophysiologic changes occurring during drowning in cold fresh water and cold salt water with reference to viability. DESIGN: Randomized, prospective, controlled submersion experiments in two contrasting cold liquids. SETTING: A laboratory at a large university-affiliated medical institution. SUBJECTS: Thirteen healthy, anesthetized mongrel dogs. Three dogs served as controls and were immersed but not submerged. The remainder were submerged in cold fresh water or cold salt water (4 degrees C). INTERVENTIONS: Catheters were placed in the femoral artery, right carotid artery and right internal jugular vein. Electrocardiogram, pneumogram, and rectal temperatures were measured continuously during submersion/immersion. MEASUREMENTS AND MAIN RESULTS: Cold water submersion with drowning produced a large initial decrease in carotid artery temperature (approximately 7.5 degrees C in the first 2 mins) compared with a minor decrease (approximately 0.8 degrees C with immersion). No significant differences were noted in the rate of decrease of temperature between drowning in fresh water and salt water. During cold fresh water drowning, aspiration produced gross hemodilution with an average increase in body weight of 16.5%. Hematocrit values, serum sodium concentrations, and osmolality decreased while serum potassium concentrations, catecholamines, and free hemoglobin increased. All measured biochemical data (except PaO2) remained at viable levels. By contrast, during cold salt water drowning, average body weight increased by only 6%, with hemoconcentration and a shrinkage of vascular volume. Hematocrit and hemoglobin values increased by 30%, but initial plasma free hemoglobin values remained unchanged. Serum sodium concentrations, osmolality, and potassium concentrations increased rapidly to critical levels. CONCLUSIONS: On submersion in cold water, all of the experimental animals developed tachypnea immediately, followed by aspiration with predictable effects. The biochemical and pathophysiologic changes in cold water drowning approximated those changes reported for warm water drowning for both fresh and salt water with one exception and continued aspiration of cold water produced extremely rapid core cooling as long as the circulation remained intact. This process of acute submersion hypothermia may protect the brain temporarily from lethal damage, as reported in cases of cold fresh water drowning. Concentrations of circulating catecholamines increased exponentially in both groups of test animals. Clinically, their acute effects on the circulation, compounded by significant hypothermia and extreme anoxia, must hamper the detection of residual circulation at rescue and may play a role in sudden death from cold water in the absence of drowning.

Animals↗
PubMed1994

Placental water content and distribution.

The percentage of total placental water (%H2O(T)), maternal (%MBV) and fetal (%FBV) blood volumes, non-vascular extracellular (%EW) and intracellular (%IW) water, and villous histology were studied in placentas from 12 normal term pregnancies after a normal vaginal delivery, 19 caesarean sections at term after a normal pregnancy and history of a previous caesarean section and 47 caesarean sections at term or preterm due to pregnancy complications. Values were derived from change in placental dry weight, maternal and fetal haemoglobin content and 51CrEDTA space after incubation of placental fragments. Normal ranges (mean +/- SD) after term vaginal delivery were: H2O(T) 83.9 +/- 0.2%, MBV 10.9 +/- 0.2%, FBV 7.4 +/- 0.9%, EW 57.3 +/- 1.3% and IW 11.2 +/- 0.6%. %H2O(T) was higher after caesarean section; other measurements were not affected. There were no differences between placentas after 33-37 and after 38-42 weeks gestation. Three of eight placentas after rhesus incompatibility had %H2O(T) above the mean +2SD of term placentas and five of 17 IUGR placentas were below the mean -2SD. The remaining placentas following maternal pre-eclampsia, hypertension, or diabetes had no apparent alteration in %H2O(T). A blind histological diagnosis of 'true' oedema was associated with both a significantly high %IW and %H2O(T). Perhaps this is due to alteration in placental cell volume regulation in certain situations.

Blood Volume↗
PubMed1993

Screening practice for familial adenomatous polyposis: the potential for regional registers.

Existing screening practice for familial adenomatous polyposis (FAP) was evaluated in 47 families with FAP notified to the West Midlands Polyposis Register between February 1988 and July 1990. Of these 269 individuals, 107 were known to be affected and 162 were at 50 per cent prior risk of developing FAP; 35 decreased affected individuals from living generations were included in the analysis. Of 105 individuals in the at-risk group aged between 12 and 40 years, only 55 (52 per cent) were under follow-up by bowel examination. Thirty-seven affected individuals had developed colorectal carcinoma before diagnosis; the incidence was three of 51 (6 per cent) in those diagnosed through screening compared with 34 of 53 (64 per cent) in the unscreened group (P < 0.001). A total of 28 individuals (26 per cent of the FAP population) died from advanced colorectal carcinoma; all were from the unscreened population. In 22 (59 per cent) of the cases of colorectal carcinoma and 17 (61 per cent) of the deaths from advanced colorectal cancer there was a positive family history of FAP; these tumours were therefore potentially preventable through screening and prophylactic surgery. Since establishing the register the median age at diagnosis of the affected patients has been reduced from 32 to 23 years (P = 0.0004) and the incidence of colorectal cancer has fallen from 35 to 14 per cent (P < 0.05). It is concluded that by providing more comprehensive case ascertainment a regional register can have a dramatic effect on this largely preventable form of colorectal cancer. Regional registers are recommended as an essential component of screening for this disease.

Adenomatous Polyposis Coli↗
PubMed1993

Culturing of primary hepatocytes as entrapped aggregates in a packed bed bioreactor: a potential bioartificial liver.

Conventional culture systems for hepatocytes generally involve cells cultured as flat, monolayer cells, with limited cell-cell contact, in a static pool of medium, unlike the liver in vivo where the parenchymal cells are cuboidal, with extensive cell-cell contact, and are continuously perfused with blood. We report here a novel bioreactor system for the culturing of primary hepatocytes with cuboidal cell shape, extensive cell-cell contact, and perfusing medium. The hepatocytes were inoculated into the bioreactor and allowed to recirculate at a rate optimal for them to collide and form aggregates. These newly-formed aggregates were subsequently entrapped in a packed bed of glass beads. The bioreactor was perfused with oxygenated nutrient medium, with controlled oxygen tension, pH, and medium perfusion rate. The hepatocytes were viable for up to the longest time point studied of 15 days in culture based on urea synthesis, albumin synthesis and cell morphology. Light microscopy studies of hepatocytes cultured for 15 days in the bioreactor showed interconnecting three-dimensional structures resembling the hepatic cell plate in the liver organ. Electron microscopy studies on the same cells revealed ultrastructure similar to the hepatocytes in vivo, including the presence of plentiful mitochondria, rough and smooth endoplasmic reticulum, glycogen granules, peroxisomes, and desmosomes. We believe that our hepatocyte bioreactor is a major improvement over conventional culture systems, with important industrial applications including toxicology, drug metabolism, and protein/peptide synthesis. The hepatocyte bioreactor concept may also be used as the basis for the development of a bioartificial liver to provide extracorporeal hepatic support to patients with hepatic failure.

Albumins↗
PubMed1993

Morphine pharmacokinetics in children following cardiac surgery: effects of disease and inotropic support.

The pharmacokinetics of morphine have not been previously studied in children following cardiac surgery for tetralogy of Fallot (TOF) or transposition of the great arteries (TGA). Morphine steady-state pharmacokinetics were studied in 21 children undergoing repair of TOF, TGA, or atrio-ventricular septal defects (AVSD). Children with TOF or TGA had increased right-sided pressures with no differences between the groups. Children with TOF had significantly faster clearance rates of morphine (1.39 +/- 0.37 L/kg/h) than children following the Fontan procedure (0.86 +/- 0.31 L/kg/h, P < 0.01). When stratifying children by their postsurgical needs for inotropic support, those needing epinephrine, dopamine, or dobutamine at more than 10 micrograms/kg/min had significantly slower clearance rates (0.73 +/- 0.3 L/kg/h) when compared to the rest of the patients (1.5 +/- 0.41 L/kg/h, P < 0.05). Because most children needing inotropic support underwent the Fontan procedure, it is conceivable that their cardiovascular status had a major impact on morphine metabolism. These results suggest a 50% reduction in morphine dosage in children requiring inotropic support following cardiac surgery.

Blood Pressure↗
PubMed1993

The trephining of bone from the iliac crest: an anterior approach.

A quick and simple method of trephining moderate amounts of cancellous bone (up to 6 cc) from the iliac crest via an anterior approach is presented. The advantages of this technique are that no muscle or ligamentous attachments are disturbed and postsurgical morbidity is low.

Adult↗