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Biomedical subjects

M Hicks

Publications and source records attributed to M Hicks.

At least 19 recordsLinked to original sources
PubMed2005

Severe retinopathy of prematurity: longitudinal observation of disease and screening implications.

PURPOSE: To test the effectiveness of our Canadian retinopathy of prematurity (ROP) screening guidelines as applied to high-risk premature infants. STUDY DESIGN: Retrospective longitudinal cohort study. SUBJECTS: A total of 969 infants were examined longitudinally between 1991 and 2000 and 46 of these infants screened were treated for severe ROP. METHODS: Data from weekly ROP screening examination results were collected from a geographical area and analysed. RESULTS: The average incidence of severe ROP requiring treatment in the population of premature infants eligible for screening was 48.3 per 1000. In all, 46 infants were treated in this cohort. The mean gestational age (GA) was 25.5 weeks of age and the mean birth weight was 750 g. The mean chronological age (CA) and postmenstrual age (PMA) at the time of first screening was 36 days and 30.7 weeks, respectively. The first identification of any ROP in this group was at a mean CA 60 days and PMA of 34.1 weeks. The mean CA and PMA of the first observation of stage 3 were 74 days and 36.3 weeks. The mean CA and PMA at the time of treatment were 86 days and 37.7 week. CONCLUSIONS: Our observations and analysis indicate the following ROP screening recommendations: infants of 28 weeks of GA or less, infants with a GA between 28 weeks and 30 weeks should have a single 'spot examination' at approximately 37 weeks of PMA (or prior to discharge from hospital) to include possible outliers; infants born with a birth weight of 1250 g or less; initial screening examination should be at 31 weeks of PMA or 4 weeks of CA, whichever is later; in the presence of any active ROP, the infant should be followed every 1-2 weeks; and stage 3 should be followed at least every 7 days.

Age Factors↗
PubMed2001

Subclinical mastitis presenting as acute, unexplained, excessive crying in an afebrile 31-day-old female.

We present a case of a 31-day-old female who presented with an acute, unexplained, episode of excessive crying. The patient had no history of fever and no fever on presentation. There was no evidence of skin erythema or swelling on presentation. Chest radiograph and computed tomography of the head were normal. Urinalysis and cerebral spinal fluid analysis were normal. The white blood cell count was within normal limits (17,400 cells/mm3). It was not until 6 hours after the onset of inconsolable crying (2.5 hours after presentation to the emergency department) that the patient's temperature rose to 38.5 degrees C (101.3 degrees F). Clinical signs of mastitis did not become appreciable until the 2nd hospital day. We review the literature on infantile mastitis and acute, unexplained, excessive crying. The importance of a thorough, conservative approach to the infant with acute, unexplained, excessive crying is discussed.

Acute Disease↗
PubMed2000

Multiple roles of the Dcdc42 GTPase during wing development in Drosophila melanogaster.

The Rho sub-family of GTPases, comprising Rho, Rac and Cdc42. regulates many biological processes, including morphogenesis, cell polarity, migration, the cell cycle and gene expression. It is important to develop genetic approaches to allow the dissection, in vivo, of the mechanisms of GTPase regulation and signal transmission, and their biological consequences. In this regard, wing development in Drosophila melanogaster is an excellent model system. To investigate the functions of the Drosophila Cdc42 GTPase (Dcdc42), we generated phenotypes during wing development, by expression of the dominant-negative N17 and L89 mutants of Dcdc42. We have identified roles for Dcdc42 in wing growth, and in cell fate choice during the development of the wing veins and the peripheral nervous system. Reduction of Dcdc42 signalling following over-expression of Dcdc42N17 resulted in a broader but more diffuse domain characterised by wing-margin sensory bristles. This was correlated with a broadened stripe of wingless expression along the dorsal-ventral boundary of third-instar wing imaginal discs. Together with genetic interactions with loss- and gain-of-function Notch alleles, these data support a role for wild-type Dcdc42 as a negative regulator of Notch signalling.

Animals↗
PubMed2000

A brain dead donor model of porcine orthotopic cardiac transplantation for assessment of cardiac allograft preservation.

BACKGROUND: We aimed to develop a large animal model of orthotopic cardiac transplantation, incorporating donor brain death, to assess new methods of preservation of the donor heart. METHODS: Brain death was achieved in the donor pig by inflation of a 20 cc subdural balloon 1 h prior to harvest. The donor heart was stored for 6 h with conventional hypothermic ischaemic preservation. It was then transplanted orthotopically into the recipient pig using the Lower and Shumway technique. One hour after reperfusion, the transplanted heart was weaned from cardiopulmonary bypass with dobutamine support. Dobutamine support was continued for up to 4 h, if required. After 6 h of physiological and biochemical evaluation, the recipient was euthanased and the heart excised for histological assessment. RESULTS: All pigs experienced the classical haemodynamic changes associated with brain death. This resulted in the release of Troponin I, consistent with myocardial injury. The donor operation was successfully completed in 11 out of 13 pigs. Six out of 11 transplanted hearts were successfully weaned from cardiopulmonary bypass, but required ongoing dobutamine support. CONCLUSIONS: This porcine model of orthotopic cardiac transplantation is a relevant and practical large animal model for the assessment of new methods of preservation of the donor heart.

Journal Article↗
PubMed2000

Standardized measurement of the future liver remnant prior to extended liver resection: methodology and clinical associations.

BACKGROUND: There is no agreement regarding the preoperative measurement of liver volumes and the minimal safe size of the liver remnant after extended hepatectomy. METHODS: In 20 patients with hepatobiliary malignancy and no underlying chronic liver disease, volumetric measurements of the liver remnant (segments 2 and 3 +/- 1) were obtained before extended right lobectomy (right trisegmentectomy). The ratios of future liver remnant to total liver volume were calculated by using a formula based on body surface area. In 12 patients, response to preoperative right trisectoral portal vein embolization was evaluated. In 15 patients who underwent the planned resection, preoperative volumes were correlated with biochemical and clinical outcome parameters. RESULTS: The future liver remnants increased after portal vein embolization (26% versus 36%, P < .01). Smaller size liver remnants were associated with an increase in postoperative liver function tests (P < .05) and longer lengths of hospital stay (P < .02). Preliminary data indicates an increase in major complications for liver volumes < or = 25% (P = .02). CONCLUSIONS: A simple method of measurement provides an assessment of the liver remnant before resection. It is useful in evaluating response to portal vein embolization and in predicating the outcome before extended liver resections.

Adult↗
PubMed1999

Comparison of the angiojet rheolytic catheter to surgical thrombectomy for the treatment of thrombosed hemodialysis grafts. Peripheral AngioJet Clinical Trial.

PURPOSE: To compare the clinical effectiveness of the AngioJet F105 rheolytic catheter to that of surgical thrombectomy for the treatment of thrombosed hemodialysis grafts. MATERIALS AND METHODS: This was a multicenter, prospective, randomized trial comparing technical success, primary patency, and complication rates. A total of 153 patients were enrolled: 82 patients in the AngioJet group and 71 patients in the surgical thrombectomy group. Patient follow-up was performed 24-48 hours, 1 month, and 6 months after the procedures. RESULTS: Technical success, as defined by the patient's ability to undergo hemodialysis treatment, was 73.2% for the AngioJet group and 78.8% for the surgical thrombectomy group (P = .41). The primary patency rates of the AngioJet group were 32%, 21%, and 15% at 1, 2, and 3 months, respectively. The primary patency rates for the surgical group were 41%, 32%, and 26% at 1, 2, and 3 months, respectively. This difference approached statistical significance (P = .053). The groups had similar complication rates-14.6% in the AngioJet group and 14.1% in the surgery group-although the surgery group had more major complications (11.3%). In the AngioJet group, there was a transient increase in plasma-free hemoglobin, which normalized within 24-48 hours. CONCLUSIONS: The AngioJet F105 catheter provides similar clinical results when compared to surgical thrombectomy for the treatment of thrombosed hemodialysis grafts. The difference in patency rates between these two techniques approached statistical significance. In addition, results of both thrombectomy methods were inferior to those suggested by the Dialysis Outcomes Quality Initiative guidelines.

Adult↗
PubMed1999

ATP-sensitive potassium channel activation mimics the protective effect of ischaemic preconditioning in the rat isolated working heart after prolonged hypothermic storage.

1. Ischaemic preconditioning (IP) can significantly reduce the extent of infarct size, contractile dysfunction and necrosis in hearts from a number of animal species. Activation of ATP-sensitive potassium channels has been implicated in this process. The aims of the present study were to determine the extent to which IP preserves haemodynamic function in the rat isolated working heart model after prolonged hypothermic storage and to examine the involvement of activation of potassium channels in this process. 2. Hearts from Wistar rats were perfused on a Langendorff apparatus. After stabilization in working mode, baseline measurements of heart rate, aortic flow, coronary flow and cardiac output were performed. Hearts were randomized to one of six treatment groups: (i) untreated control; (ii) IP; (iii) 3 min perfusion with 200 mumol/L pinacidil; (iv) pinacidil vehicle; (v) 3 min perfusion with 10 mumol/L glibenclamide before IP; and (vi) 3 min perfusion with glibenclamide then pinacidil. Hearts were stored in an extracellular-based preservation solution for 6 or 12 h at 2-3 degrees C, remounted on the perfusion apparatus, stabilized as before and then haemodynamic measurements were repeated, after which time heart water contents were determined. 3. Recovery of haemodynamic function was markedly enhanced in the IP and pinacidil-treated groups compared with untreated and vehicle controls. These beneficial effects were completely blocked by glibenclamide. These results suggest that strategies for activating potassium channels in donor hearts may protect organs during hypothermic storage prior to transplantation.

Adenosine Triphosphate↗
PubMed1998

Cardioprotective effects of pinacidil pretreatment and lazaroid (U74500A) preservation in isolated rat hearts after 12-hour hypothermic storage.

BACKGROUND: Two important processes in the preservation of the function of donor hearts are the maintenance of ATP-sensitive potassium channel activity during myocardial ischemia and the scavenging of reactive oxygen species formed during reperfusion. The aim of this study was to compare the effect of three protocols on the preservation of hemodynamic function in isolated rat hearts after hypothermic storage. These protocols were: (1) pretreatment of the heart with a potassium channel opener (200 microM pinacidil); (2) storage of the heart in an aspartate-enriched extracellular cardioplegic solution containing the lazaroid antioxidant, U74500A (30 microM); and (3) a combination of protocols 1 and 2. METHODS: Hearts from Wistar rats were perfused on a Langendorff apparatus. After stabilization in working mode, baseline measurements of heart rate, coronary and aortic flow, and cardiac output were performed. Hearts (n=6 in each group) were then randomized to protocols 1-3, untreated controls, or vehicle-treated controls. Hearts were stored in extracellular-based preservation solution for 12 hr at 2-3 degrees C, remounted on the perfusion apparatus, and stabilized as before; hemodynamic measurements were then repeated. RESULTS: Recovery of hemodynamic function was enhanced by pinacidil pretreatment or incorporation of lazaroid in the storage solution, but the combination of these two treatments produced the best results. CONCLUSIONS: Combined pharmacological activation of ATP-sensitive potassium channels before cardioplegia and the addition of U74500A to the preservation solution is associated with significantly enhanced hemodynamic function in the isolated rat heart after 12 hr of hypothermic storage. These data suggest a novel use for these agents in the transplantation context.

Animals↗
PubMed1998

Heterogeneity of CD44 expression among human B-cell subpopulations.

CD44 is a widely distributed cell surface glycoprotein that participates in a number of cellular adhesion and signal transduction processes. Germinal center B cells express very low levels of CD44, whereas their precursors and differentiation products express much higher levels. In immunofluorescence studies comparing 20 antibodies classified as being against the hematopoietic isoform of CD44, one antibody, A1G3, was unreactive with germinal center B cells, whereas the other antibodies showed low intensity but definite reactivity. Western blotting and sequential immunoprecipitation studies of lysates from density-separated lymphocyte fractions showed two bands that were differentially expressed and reacted differently with A1G3 compared with the other CD44 antibodies. These results suggest that germinal center B cells and non-germinal center B cells express different forms of CD44. Of 21 malignant B-cell populations examined, 5 showed reactivity with a "standard" CD44 reagent and significantly reduced reactivity with A1G3, while one sample showed the opposite pattern and the remainder were positive for both reagents. Of 10 cell lines studied, 5 were differentially stained by A1G3 and a standard CD44 antibody. PCR amplification of reverse transcribed mRNA from sorted human tonsil B-cell subpopulations and Southern blotting showed that B cells express a number of splice isoforms of CD44. These results demonstrate that B cells express multiple forms of CD44; both splice insert isoforms and variants distinguished by A1G3; the form of CD44 expressed depends on B-cell differentiation state.

Antibodies, Monoclonal↗
PubMed1998

The nitric oxide donor, diethylamine NONOate, enhances preservation of the donor rat heart.

BACKGROUND: Ischemia/reperfusion injury to transplanted organs may be associated with loss of endothelial release of nitric oxide. The aim of this study was to determine whether supplementation of an extracellular-based cardioplegic solution in routine clinical use at our institution with nitric oxide (as diethylamine NONOate) enhanced poststorage functionality of an isolated working heart model. METHODS: Excised hearts were ligated to an aortic cannula and immediately perfused retrogradely with oxygenated Krebs solution at a hydrostatic pressure of 100 cm H2O at 37 degrees C. This preparation was then converted to a working system by switching the supply of perfusate from the aorta to a left atrial cannula at a filling pressure of 15 cm H2O. After a 1-minute stabilization period, baseline measurements of heart rate, aortic flow, coronary artery flow, and cardiac output were performed. Oxygenated cardioplegic solution (0.1 micromol/L), with or without NONOate, was then infused into the coronary circulation. Hearts were then stored in the same solutions for 6 or 12 hours at 2 degrees to 3 degrees C. The hearts were then remounted on the perfusion apparatus and reperfused as before, and hemodynamic measurements were repeated. Water content of the hearts were then determined. RESULTS: Addition of the nitric oxide donor significantly improved all hemodynamic parameters measured after 12 hours storage and aortic flow at 6 hours storage compared with the untreated control groups. There was no significant difference between the water contents of the NONOate-treated and control groups. CONCLUSIONS: The presence of the nitric oxide donor diethylamine NONOate was associated with significantly better preservation of coronary artery flow and cardiac function in the isolated rat heart after a 12-hour period of hypothermic storage and suggests a novel use for this family of compounds in the transplantation context.

Animals↗
PubMed1997

Assessing the sequence specificity in the binding of Co(III) to DNA via a thermodynamic approach.

The interaction specificities of Co(III) with DNA were investigated via consideration of thermodynamic characteristics of the duplex to single strand transition for DNA oligomers incubated in the presence of [Co(NH3)5(OH2)](ClO4)3. It has previously been demonstrated that incubation of the DNA oligomer [(5medC-dG)4]2 with this cobalt complex leads to coordination of the cobalt center to the DNA, presumably at N7 of guanine bases [D. C. Calderone, E. J. Mantilla, M. Hicks, D. H. Huchital, W. R. Murphy, Jr. and R. D. Sheardy, (1995) Biochemistry 34, 13841]. In this report, DNA oligomers of different sequence were incubated with [Co(NH3)5(OH2)](ClO4)3 via protocols developed previously and the treated oligomers were subjected to thermal denaturation for comparison to the untreated oligomers. The DNA oligomers were designed in order to investigate the sequence specificity, if any, in the reaction of the cobalt complex with DNA. The values of Tm, delta HvH, and delta n (the differential ion binding term) obtained from the thermal denaturations were used to assess the sequence specificity of the interaction. For all oligomers, treated or untreated, Tm and delta HvH vary linearly with log [Na+] and hence the value of delta n is a function of the Na+ concentration. The results indicate no significant reaction between the cobalt complex and oligomers possessing isolated -GA- or -CG- sites; however, the thermodynamic characteristics of DNA oligomers possessing either an isolated -GG- site or an isolated -GC- site were altered by the treatment. Atomic absorption studies of the treated oligomers demonstrate that only the DNA oligomers possessing isolated -GG- or -GC- sites bind cobalt. Hence, the changes in the thermodynamic properties of these oligomers are a result of cobalt binding with a remarkable sequence specificity.

Binding Sites↗
PubMed1996

The effect of prolonged pneumoperitoneum on renal function in an animal model.

BACKGROUND: Prolonged, increased intra-abdominal pressure (IAP) during laparoscopic surgery has been associated with oliguria and anuria. STUDY DESIGN: The objective of this study was to evaluate the effects of various levels of IAP on renal function. Ten groups of three adult female farm pigs were given a general anesthetic, followed by establishment of an IAP of 0, 5, 10, 15, or 20 mm Hg with CO2, 20 mm Hg with argon gas, abdominal wall lift device, renal vein occlusion (RVO), 15 mm Hg with CO2 plus dopamine administration at 2 microgram/kg/minute, or 20 mm Hg retroperitoneal CO2 insufflation. The following studies were recorded: baseline central venous pressure (CVP), pulmonary wedge pressure (PWP), cardiac output (CO), renal vein flow (RVF), renal artery pressure (RAP), selective urine output (UO), urinary osmolarity, and creatinine clearance; the parameters were repeated every 30 minutes for the four hours of the IAP study and two hours after release of the IAP. RESULTS: The results were analyzed within two main IAP groups: less than 15 mm Hg and greater than or equal to 15 mm Hg. There was no clinically significant variation in the CVP, PWP, and RAP. The CO decreased slightly and this was more significant in the greater than or equal to 15 mm Hg group. The RVF and UO decreased concomitantly and significantly in the greater than or equal to 15 mm Hg group. Even after two hours of desufflation, the RVF did not return to baseline, although the UO improved. Creatinine clearance decreased significantly in the greater than or equal to 15 mm Hg group. The RVO group exhibited similar changes in the study parameters as those seen in the greater than or equal to 15 mm Hg group, although the RVF did not improve on release of the renal vein in the RVO group. Changes were the same with an argon or CO2 IAP of 20 mm Hg. The abdominal wall lift device had an associated decrease in RVF at 15 KG force but no alteration in UO. Retroperitoneal insufflation resulted in the same decrease in RVF and UO as seen with the same IAP. Dopamine did not afford a protective effect on UO during an IAP of 15 mm Hg. CONCLUSIONS: The decreased UO during prolonged IAP greater than or equal to 15 mm Hg in the animal model is associated with a corresponding decrease in RVF, but does not appear to be associated with any permanent renal derangement nor any transient histologic changes.

Animals↗
PubMed1996

Ischemic preconditioning enhances donor lung preservation in the rat.

BACKGROUND: Ischemic preconditioning achieved by brief periods of ischemia and reperfusion before a prolonged period of ischemia can significantly reduce the extent of cardiac damage in many mammalian species and human beings. In this study we used a rat model of single lung transplantation to show that ischemic preconditioning also occurs in the lung. METHODS: Rats randomly selected for ischemic preconditioning had their left main bronchus and pulmonary artery occluded for 5 minutes, followed by 10 minutes of reperfusion and ventilation. Lungs of control rats were ventilated for 15 minutes. The lungs were perfused with University of Wisconsin solution, then heart and lungs were excised en bloc and stored in University of Wisconsin solution at 0 degree C for 6 or 12 hours. After left pneumonectomy, the left lung of the donor was then implanted into the recipient via left thoracotomy. After 1 hour of ventilation and reperfusion, a right pneumonectomy was performed making the animal completely dependent on the transplanted lung. Samples of arterial blood from the left ventricle were then taken for arterial oxygen tension and arterial carbon dioxide tension determination. Water contents of the donor lungs were measured before and after reperfusion. Thiobarbituric acid reactive substances were measured in the right donor lung after storage. RESULTS: Lungs transplanted after 12 hours of storage had profoundly impaired gas exchange (arterial oxygen tension = 34 +/- 5; arterial carbon dioxide tension = 69 +/- 7 mm Hg) compared with the normal levels in the 6-hour storage group (arterial oxygen tension = 308 +/- 22; arterial carbon dioxide tension = 17 +/- 1 mm Hg). Ischemic preconditioning significantly improved gas exchange in the 12-hour storage group (arterial oxygen tension = 83 +/- 11; arterial carbon dioxide tension = 40 +/- 4 mm Hg). Ischemic preconditioning also significantly decreased thiobarbituric acid reactive substances formation at both 6- and 12-hour storage. CONCLUSIONS: These results show that the phenomenon of ischemic preconditioning occurs in the lung and that it may reduce injury to the donor lung during prolonged cold ischemic storage.

Animals↗
PubMed1995

Binding of Co(III) to a DNA oligomer via reaction of [Co(NH3)5(OH2)]3+ with (5medC-dG)4.

The interaction specificities of cobalt(III) ammines with the self-complementary eight-base pair DNA oligomer (5medC-dG)4 have been investigated. Standard protocol for preparing DNA samples calls for heat annealing the DNA oligomer in phosphate buffer in the absence or presence of cobalt(III) ammine complex for 2 min at 80 degrees C, followed by slow cooling to 25 degrees C. An alternative method for DNA preparation is incubation of the oligomer in the presence of the cobalt(III) complex at 37 degrees C followed by exhaustive dialysis. The conformational properties of the thus-treated DNA oligomer were determined by inspection of the UV and CD spectra at 25 and 95 degrees C and thermal denaturation studies. With heat annealing in the absence of any cobalt(III) complex, (5medC-dG)4 assumes a double-stranded, right-handed B conformation at 25 degrees C. Upon heat annealing in the presence of 200 microM [Co(NH3)6]3+, (5medC-dG)4 assumes a double-stranded, left-handed Z conformation at 25 degrees C. In contrast, the CD and UV spectra of (5medC-dG)4 heat annealed in the presence of 200 microM [Co(NH3)5(OH2)]3+ are consistent with a distorted B-like conformation at 25 degrees C. Incubation of the oligomer in the presence of [Co(NH3)5(OH2)]3+ results in modification of the conformational properties of the oligomer at both 25 and 95 degrees C relative to the untreated oligomer. The extent of modification depends upon the incubation concentration of [Co(NH3)5-(OH2)]3+ and the reaction time. Atomic absorption (AA) analyses of these treated DNA samples indicate a high degree of cobalt association to the oligomer.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1995

Components of life model in practice.

This paper attempts to cover the stages recognised as being part of the research process in order to investigate the problem related to the lack of individualised patient care documentation and supporting theoretical framework, which is both understood and accepted by the staff within Accident and Emergency (A & E). With the advent of the United Kingdom Central Council's (UKCC) document Standards of Record Keeping (1993), there is now greater need for a model to be implemented and accepted by those working in the department. The Components of Life model was introduced following a literature search, as this seemed to be a potential solution to the problem, since it emphasises the individual practising self-care activities in order to maintain independence. To initiate staff to the Components of Life model, a half study day was organised on the subject of models of care within A & E. Jones was invited to discuss his approach to A & E nursing care. Subsequently, a draft document relating to nursing care was created using the Components of Life model as a framework. The initial draft was followed with a printed document which was put into use for a trial period of 4 weeks, followed by a review. The review collected both positive and negative comments from the staff, the negative proved to be the most constructive as they served to make improvements within the care plan. Perhaps the most important success as a result of completing this project is that of increased staff enthusiasm and motivation--especially in wanting to make the documentation work.

Emergency Nursing↗