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Biomedical subjects

J Hutchison

Publications and source records attributed to J Hutchison.

At least 19 recordsLinked to original sources
PubMed2006

Hypothermia pediatric head injury trial: the value of a pretrial clinical evaluation phase.

BACKGROUND: The utility of a pretrial clinical evaluation or run-in phase prior to conducting trials of complex interventions such as hypothermia therapy following severe traumatic brain injury in children and adolescents has not been established. METHODS: The primary objective of this study was to prospectively evaluate the ability of investigators to adhere to the clinical protocols of care including the cooling and rewarming procedures as well as management guidelines in patients with severe traumatic brain injury (Glasgow Coma Scale<or=8) treated with 24 h of hypothermia therapy. A secondary objective was to evaluate the ability of study research assistants to complete the study case report form using a procedures manual. The study was conducted at 18 sites in Canada, the United Kingdom and France prior to proceeding to a randomized controlled trial (RCT). After 2 patients were enrolled at each center, an independent clinical evaluation committee examined the process of care and the completeness of data collection. Centers were permitted to enroll patients in the RCT once they met pre-established adherence criteria. RESULTS: Seventeen of the 18 centers completed the pretrial clinical evaluation phase demonstrating compliance with study procedures and proceeded to an RCT of hypothermia therapy. One center enrolled only 1 patient in the pretrial clinical evaluation phase due to small numbers of patients with traumatic brain injury, and therefore, did not proceed to the RCT. Three centers were required to enroll more than 2 patients in the pretrial clinical evaluation phase prior to proceeding to the RCT because of problems with adherence to the clinical protocols at two centers and the training of new study personnel at another center. Of the 39 patients enrolled during the pretrial clinical evaluation phase, 8 (20.5%) died and 22 (62.9%) had a good outcome defined as normal, mild or moderate disability assessed using the Pediatric Cerebral Performance Category score at 6 months following injury. DISCUSSION: The pretrial clinical evaluation phase was useful to ensure compliance with complex hypothermia therapy and consensus-based clinical management guidelines of care successfully implemented across 17 of 18 centers. This study maneuver allowed us to complete a subsequent RCT in 225 children following severe traumatic brain injury.

Algorithms↗
PubMed2006

Femoral head viability after Birmingham resurfacing hip arthroplasty: assessment with use of [18F] fluoride positron emission tomography.

BACKGROUND: Total hip resurfacing has become increasingly popular over the last decade. There remains concern about the effect of the surgical approach on femoral head viability and the role of resurfacing in the management of established osteonecrosis. In view of these concerns, we examined femoral head viability following resurfacing through a modified anterolateral approach. METHODS: The viability of the femoral heads of ten patients who had undergone successful unilateral Birmingham hip resurfacing was assessed with use of positron emission tomography in conjunction with the injection of fluorine at a mean of twenty months after surgery. For each patient, in both the hip that had undergone resurfacing and the contralateral nonresurfaced hip, activity was measured in four regions of interest: the lateral aspect of the femoral head, the medial aspect of the femoral head, the lateral aspect of the femoral neck, and the proximal aspect of the femur. The uptake of fluorine in each area was converted to standard uptake volumes. RESULTS: No areas of osteonecrosis were seen in the femoral head of any patient. There were no significant differences in the standard uptake volumes as measured in the four regions of the nonresurfaced hips, whereas the median values were higher in all four regions of the resurfaced hips. The difference between the values in the resurfaced hips compared with those in the nonresurfaced hips was only significant (p < 0.05) in the lateral aspect of the femoral head. CONCLUSIONS: This study establishes positron emission tomography in conjunction with injection of fluorine as a possible modality for the assessment of femoral head viability after hip resurfacing. Viability following successful Birmingham hip resurfacing performed through a modified anterolateral approach has also been demonstrated. The increase in bone activity that was seen in the resurfaced hips in our study group may be related to bone remodeling or reperfusion of small areas of osteonecrosis. This technique offers the potential to study femoral head perfusion and viability following all types of resurfacing. LEVEL OF EVIDENCE: Diagnostic Level IV. See Instructions to Authors on jbjs.org for a complete description of levels of evidence.

Adult↗
PubMed2005

Peri-acetabular radiolucent lines: inter- and intra-observer agreement on post-operative radiographs.

Peri-acetabular radiolucent lines (RLLs) seen on "early" post-operative radiographs have been identified as a potential predictor of long-term implant performance. This study examines the inter- and intra-observer variation encountered when assessing such radiographs. Four consultant orthopaedic surgeons assessed the presence, extent and width of RLLs in 220 radiographs performed on 50 patients taken one to two weeks, six weeks, six months and one year following surgery. Inter-observer agreement was fair at 7-14 days but improved to moderate to good in films at six and 12 months. Intra-observer agreement was moderate to good at 7-10 days but again improved to good at 6 and 12 months. When only the presence or absence of RLLs was considered, both inter-observer and intra-observer agreement improved for both the six-month and one-year radiographs. This experiment shows that caution must be used for the interpretation of RLLs on hip radiographs taken during the very early post-operative period. We recommend that films taken at least six weeks to six months following surgery should be used for assessment to reduce observer variation. For optimum results, a single experienced observer should do the assessment with a simple classification.

Aged↗
PubMed2003

Early dialysis in a neonate with intrauterine lisinopril exposure.

In general, angiotensin converting enzyme (ACE) inhibitors should be discontinued in pregnancy, as they can induce an ACE fetopathy. For the treatment of the latter, early peritoneal dialysis is recommended for in utero exposure to captopril and enalapril, although the outcome is poor. Early peritoneal dialysis has not previously been reported for lisinopril induced multiorgan failure. A case is reported in which treatment was given on postnatal day 3. The patient recovered from oligoanuria to almost normal renal function, and heart, brain, and musculoskeletal injury was reversible. This is despite relatively poor clearance of the drug through peritoneal dialysis. Analysis of the pharmacokinetic data suggests that haemodialysis or haemofiltration would be more efficacious for removal of the drug, and these treatments should be performed if available.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

A role for platelets and endothelial selectins in tumor necrosis factor-alpha-induced leukocyte recruitment in the brain microvasculature.

The mechanisms mediating leukocyte recruitment into the cerebral nervous system during inflammation are still poorly understood. The objective of this study was to investigate the leukocyte recruitment in the brain microcirculation by intravital microscopy. Superfusion of the brain with artificial cerebrospinal fluid did not induce leukocyte rolling or adhesion. However, intraperitoneal tumor necrosis factor-alpha (TNF-alpha) caused marked leukocyte rolling and adhesion in the brain microcirculation. Histology revealed that the recruitment was primarily of neutrophils. Both E- and P-selectin were required for TNF-alpha-induced leukocyte recruitment, as rolling was reduced after treatment with either anti-E- or anti-P-selectin antibody and eliminated in E- or P-selectin-deficient mice. A significant increase in brain P- and E-selectin expression was seen after TNF-alpha treatment, but both were an order of magnitude less than in any other tissue. We observed significant platelet paving of TNF-alpha-stimulated endothelium and found that anti-platelet antibody reduced leukocyte rolling and adhesion, as did acetylsalicylic acid (aspirin). However, depletion of platelets did not reduce cerebral P-selectin expression. Moreover, chimeric mice lacking P-selectin on endothelium but not platelets had significantly decreased P-selectin expression and reduced leukocyte recruitment in the brain. This suggests a role for endothelial P-selectin in cerebral leukocyte recruitment. In conclusion, TNF-alpha-induced neutrophil recruitment into the brain requires both endothelial E-selectin and P-selectin as well as platelets, but platelet P-selectin was not a major contributor to this process.

Animals↗
PubMed2000

Indomethacin and cyclosporin a inhibit in vitro ischemia-induced expression of ICAM-1 and chemokines in human brain endothelial cells.

Brain inflammation has been implicated in the development of brain edema and secondary brain damage in ischemia and trauma. Mechanisms involved in leukocyte infiltration across the blood-brain barrier are still unknown. In this study, we show that human cere-bromicrovascular endothelial cells (HCEC) subjected to a 4 h in vitro ischemia (hypoxia + glucose deprivation) followed by a 4-24 h recovery express elevated levels of ICAM-1, IL-8, and MCP-1 mRNAs (semi-quantitative RT-PCR) and secrete increased amounts of the immunoreactive chemokines IL-8 and MCP-1 (ELISA). The ischemia-induced expression of ICAM-1 in HCEC, and the expression/release of IL-8 and MCP-1 in HCEC were abolished by the non-steroid anti-inflammatory drug, indomethacin (100-300 microM). The immunosuppressant cyclosporin A (50 microM) partially reduced the ischemia-stimulated IL-8 and MCP-1 secretion by HCEC. Both indomethacin and cyclosporin A also inhibited the ischemia-induced neutrophil chemotaxis elicited by HCEC media. The study indicates that in vitro ischemia augments the expression of adhesion molecules and leukocyte chemoattractants at the site of the BBB. This ischemic pro-inflammatory activation of HCEC may constitute a key event in initiating post-ischemic inflammation, and it can be suppressed by the anti-inflammatory drugs, indomethacin and cyclosporin A.

Blood-Brain Barrier↗
PubMed2000

A bench-top method for evaluating modular total hip component combinations.

A modular total hip prosthesis allows the surgeon to vary head size, neck length, and acetabular coverage. Different combinations, however, may increase the risk of impingement of the prosthesis neck on the acetabular liner, leading to dislocation. We developed a bench-top model to test different modular component combinations to determine how far the femoral component could travel within the acetabular liner before impingement led to dislocation. We tested two hip systems, each from a different manufacturer. Certain components increased the risk of impingement and dislocation: skirted necks, smaller heads, and lipped liners. While the contribution of each component was small, the risk was additive, so that the combination of a small head with a skirted neck in a lipped liner actually reduced the available range of motion by 18 degrees, from 146 degrees to 128 degrees, in the first system, and by 13 degrees, from 156 degrees to 143 degrees in the other. This method could be adapted to test a wide range of component configurations, from a number of manufacturers. These findings may be useful in avoiding potentially unstable configurations when given a choice of modular components.

Hip Prosthesis↗
PubMed2000

Mycoplasma pulmonis genital disease: effect of rat strain on pregnancy outcome.

BACKGROUND AND PURPOSE: Mycoplasma pulmonis is a natural pathogen of the respiratory and genital tracts of rats. Differential susceptibility and severity of the respiratory form of the disease, known as murine respiratory mycoplasmosis (MRM), exist between rat strains. We now report that specific rat strains vary in susceptibility to genital tract infection and pregnancy outcome. METHODS: Specific-pathogen-free (SPF) female F344, LEW, Wistar (WIS) and Sprague Dawley (SD) rats were intravaginally inoculated with 3 x 10(7) colony-forming units (CFU) of M. pulmonis strain X1048 or sterile diluent, and allowed to breed at 10 days after inoculation. Pregnant dams and pups were necropsied within 24 hours of parturition. At necropsy, culture for M. pulmonis was performed on dam and pups, and adverse effects on pregnancy outcome were assessed by determination of the incidence of infertility, fetal resorption, stillbirths, changes in litter size, and pup birth weight. Blood from dams was collected prior to inoculation and at time of necropsy for measurement of IgM and IgG antibodies to M. pulmonis. RESULTS: At time of necropsy, WIS (50%) and SD (60%) dams had a higher frequency of M. pulmonis culture positivity in the genital tract than did LEW (22.2%) and F344 (17.6%) dams. Dams that were still infected with M. pulmonis at time of necropsy had various complications. The SD rats had the greatest degree of adverse effects on pregnancy outcome, which were: infertility, decreased litter size (P < or = 0.01), decreased pup birth weight (P < or = 0.01), increased frequency of resorptions, stillbirths (P < or = 0.05), and the highest rate of pup pulmonary infection (23.1%) (P < or = 0.001). Despite a 50% colonization rate, WIS dams were the least adversely affected. The WIS pups born from M. pulmonis. infected dams had slight decrease in birth weight, and only 6% had pulmonary infections. The LEW infected dams developed infertility and lower numbers of liveborn pups without evidence of vertical transmission. The F344 infected dams had lower numbers of liveborn pups that were smaller than their control counterparts, and none had pulmonary infections. None of the animals had detectable IgM and IgG antibodies to M. pulmonis before inoculation. At time of necropsy, all animals inoculated with M. pulmonis developed significantly (P < or = 0.001) higher amounts of M. pulmonis IgG and IgM antibodies, with SD rats developing the highest amounts (P < or = 0.005). CONCLUSIONS: Both F344 and LEW rats are more resistant to vaginal inoculation with M. pulmonis than are WIS and SD rats. However, only SD dams suffered severe adverse effects on pregnancy outcome. The SD dams also had the greatest IgM and IgG antibody response to M. pulmonis. Our studies clearly indicate differences among rat strains in their susceptibility to vaginal inoculation with M. pulmonis and in secondary complications associated with infection. This system may be a useful model for determining host-specific factors that influence the outcome of natural mycoplasmal infections of the genital tract.

Animals↗
PubMed1999

Increased expression of bioactive chemokines in human cerebromicrovascular endothelial cells and astrocytes subjected to simulated ischemia in vitro.

Leukocyte infiltration into the brain has been implicated in the development of ischemic brain damage. In this study, simulated in vitro ischemia/reperfusion and IL-1beta were found to up-regulate both the expression of intercellular adhesion molecule- (ICAM-1) in cultured human cerebromicrovascular endothelial cells (HCEC) and the adhesion of allogenic neutrophils to HCEC. Both HCEC and human fetal astrocytes (FHAS) also responded to IL-1beta and to in vitro ischemia/reperfusion by a pronounced up-regulation of IL-8 and MCP-1 mRNA and by increased release of IL-8 and MCP-1 in cell culture media. FHAS were found to release 30-times higher levels of MCP-1 than HCEC under both basal and ischemic conditions. However, 100 u/ml IL-1beta induced greater stimulation of both IL-8 and MCP-1 secretion in HCEC (50 and 20 times above controls, respectively) than in FHAS (three and two times above controls, respectively). IL-8 was the principal neutrophil chemoattractant released from IL-1beta-treated HCEC, since IL-8 antibody completely inhibited neutrophil chemotaxis enticed by HCEC media. However, the IL-8 antibody neutralized only 50% of IL-1beta-stimulated neutrophil chemoattractants released from FHAS, and 40%-60% of ischemia-stimulated chemotactic activity released by either HCEC or FHAS. These results suggest that simulated in vitro ischemia, in addition to IL-8 and MCP-1, stimulates secretion of other bioactive chemokines from HCEC and FHAS.

Astrocytes↗
PubMed1997

The induction of ICAM-1 in human cerebromicrovascular endothelial cells (HCEC) by ischemia-like conditions promotes enhanced neutrophil/HCEC adhesion.

Ischemic brain injury is exacerbated by leukocyte infiltration and formation of vasogenic edema. In this study we demonstrate that intercellular adhesion molecule-1 (ICAM-1) is dramatically (3 to 15-fold) up-regulated in human cerebromicrovascular endothelial cells (HCEC) by a 16 h exposure to the cytokine, IL-1 beta (50-200 u/ml), the phorbol ester, TPA (1-100 nM), or by simulated in vitro ischemia/reperfusion. These treatments also significantly increased the adhesion of allogeneic neutrophils to HCEC monolayers. Both IL-1 beta- and TPA-induced expression of ICAM-1 and increased neutrophil adhesion to HCEC were inhibited by the transcriptional inhibitor, actinomycin D (AcD; 1-10 micrograms/ml), and by an anti-ICAM-1 antibody (ICAM-1 Ab). By contrast, ischemia-induced neutrophil adhesion was only slightly affected by AcD and ICAM-1 Ab alone, but it was abolished by the combination of anti-ICAM-1 and anti-CD18 antibodies. The increase in surface expression of ICAM-1 and neutrophil adhesion by IL-1 beta, TPA and ischemia were significantly reduced by the cyclo-oxygenase (COX) inhibitors, indomethacin (100-300 microM) and dexamethasone (10-50 microM). These results indicate that ICAM-1 expression in HCEC can lead to enhanced neutrophil adhesion and that COX activation in HCEC likely plays a role in the processes by which leukocyte adhesion and recruitment take place in the brain during inflammation and ischemia in vivo.

Blood-Brain Barrier↗
PubMed1994

Lower anion gap increases sensitivity in predicting elevated lactate.

OBJECTIVE: The normal reference range for the anion gap (AG) has recently been questioned by several authors. Lowering the upper limit of normal of the AG has been found to be more sensitive in predicting elevated lactate in critically ill adults. The objectives of this study are i) to define a new upper limit of normal of the AG in a study population of healthy adult volunteers, ii) to determine the sensitivity, specificity, the positive predictive value and the negative predictive value of the new upper limit for AG in detecting elevated lactate in critically ill children and to compare these results to the old upper limit of normal of AG (16 mmol/l), iii) to construct a receiver-operating-characteristic (ROC) curve for anion gap as a predictor of elevated lactate, iv) to determine the relationship between anion gap and serum lactate levels in critically ill patients. DESIGN: A prospective, cohort study. SETTING: Paediatric Intensive Care Unit of a University Hospital. SUBJECTS: Part I: Convenience sample of healthy adult volunteers to provide a reference range for anion gap calculation. Part II: Consecutive children admitted to the Paediatric Intensive Care Unit who had lactate levels measured for clinical reasons. MEASUREMENTS: Part I: Electrolytes and blood gases were measured from blood samples drawn from 25 adult volunteers. The reference range for AG was calculated using the equation, AG = Na - (Cl + HCO3). The upper limit of normal was calculated as mean + 2 SD. Part II: Eligible ICU patients were included in this study if they had lactate, electrolytes and blood gases obtained simultaneously. The AG was calculated as above. The new upper limit of normal AG was compared to an AG of 16 for diagnosing an elevated plasma lactate. RESULTS: The mean anion gap in the normal population was 9.4 +/- 1 mmol/l with 11 mmol/l being used as the new upper limit of normal. Thirty-six ICU patients had 189 arterial blood samples from which lactate, electrolytes and blood gas were measured simultaneously. The sensitivity, specificity, positive predictive value and negative predictive value of using an AG of 11 mmol/l as the upper limit of normal were 86%, 40%, 65% and 69% respectively, compared to 49%, 84%, 80% and 55% respectively using the upper limit of normal of AG of 16 mmol/l. The ROC curve supported lowering the upper limit of normal for the anion gap to predict an elevated lactate. There was a linear relationship between anion gap and serum lactate levels. CONCLUSIONS: An AG of 11 mmol/l as the upper limit of normal has a higher sensitivity and higher negative predictive value but lower specificity and lower positive predictive value for detecting elevated lactate in critically ill children.

Acid-Base Equilibrium↗
PubMed1993

Cellular aspects of corpus luteum function in the primate.

The primate corpus luteum produces progesterone for a period of 14-16 days, at which time, in non-fertile cycles, steroidogenesis ceases and the tissue regresses. Studies completed in this laboratory have established that while luteinizing hormone (LH) is necessary to maintain luteal steroidogenesis, changes in LH secretion are not causal to luteolysis. The studies presented here demonstrate that luteal cell synthetic capacity, as reflected in steady-state levels of messenger ribonucleic acid (mRNA) encoding steroidogenic enzymes, is maximal shortly after ovulation and steadily declines thereafter, independently of progesterone and LH secretion. In addition, the loss of luteal mRNA expression for steroidogenic enzymes following LH withdrawal occurs 24 h after the decline in progesterone levels. Finally, the detection of mRNA encoding vascular endothelial growth factor within the corpus luteum throughout the luteal phase in the subhuman primate may provide the first identification of a potential secreted, non-steroidal factor responsible for the vast degree of angiogenesis that occurs within the corpus luteum.

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

The clinicopathologic, light, and scanning electron microscopic features of eperythrozoonosis in four naturally infected llamas.

The hematologic, biochemical, and light and scanning electron microscopic features of eperythrozoonosis in four llamas are described. One female and three male yearling llamas were presented for evaluation of chronic weight loss. Three of four llamas had historical evidence of chronic inflammatory conditions. On examination, multiple clinical problems were apparent, including poorly to non-regenerative anemia, inflammatory disease, and hypoproteinemia. Coccoid- and ring-shaped basophilic organisms were present on the erythrocytes of all the llamas. On scanning electron microscopy, individual, pairs, and clusters of coccoid-shaped organisms were present on the erythrocytes. The organisms measured 0.4 to 0.6 micron in diameter and caused no marked deformation of the erythrocyte membrane. A rare organism could be found that produced a slight indentation into the erythrocyte membrane. The light and scanning electron microscopic morphologic features suggested that the organism was an Eperythrozoon. Serial evaluation of serum iron concentrations of the llamas showed a decrease serum iron in all animals, with a concurrent decrease in the total iron binding capacity and percent transferrin saturation in two of the llamas. Common abnormalities seen on serum electrophoresis included a decrease in albumin and beta serum fraction in all llamas and a decrease in the gamma globulin fraction of two individuals.

Anemia↗
PubMed1989

Differential effects of photoperiodic history on the responses of gonadotrophins and prolactin to intermediate daylengths in the male Syrian hamster.

The effect of photoperiodic history on the neuroendocrine response to intermediate daylengths (11-13.5 hr of light) was investigated in the male Syrian hamster. The duration of the nocturnal peak of pineal melatonin content was inversely proportional to photoperiod and independent of photoperiodic history. Serum levels of prolactin were lower in animals exposed to shorter photoperiods. Photoperiodic history had little effect on the response of serum prolactin to intermediate daylengths. Serum luteinizing hormone (LH) concentrations were also lower in shorter photoperiods, but in addition were sensitive to the direction of photoperiodic change, so that a single photoperiod could be interpreted as either stimulatory or inhibitory to LH secretion. This effect of photoperiodic history was expressed at intermediate photoperiods with 12-13.5 hr of light. The sensitivity of serum follicle-stimulating hormone (FSH) levels to photoperiodic history was masked by an early onset of photorefractoriness. Testicular size and serum testosterone levels revealed weaker effects of photoperiodic history; these were attributed to the dissociation between gonadotrophin and prolactin secretion induced by intermediate daylengths. The contrasting effects of photoperiodic history on the secretion of LH and prolactin may represent the expression of multiple photoperiodic time-measuring systems.

Aging↗