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Biomedical subjects

J A Murray

Publications and source records attributed to J A Murray.

At least 55 records · Page 3Linked to original sources
PubMed2000

Iatrogenic esophagitis.

A variety of medications have been reported to cause esophageal injury. Nearly 1000 cases have probably been described in the past 30 years, and this is a vast under-representation. Pill-induced esophageal injury is also associated with many underlying esophageal diseases. This review addresses the etiology, diagnosis, and clinical features of pill-induced esophageal injury as well as the specific medications that have been reported to cause it. Ways to prevent esophageal injury, including better instructions to patients who are prescribed such medications, are also discussed.

Capsules↗
PubMed2000

Control of plant growth and development through manipulation of cell-cycle genes.

The plant embryo is a relatively simple structure consisting of a primordial shoot and root, whose development is frozen in the form of a seed. Most development of the mature plant takes place post-embryonically, and is the consequence of cell division and organogenesis in small regions known as meristems, which originate in the embryonic shoot and root apices. Significant recent progress has been made in understanding the mechanisms that control the plant cell cycle at a molecular level, and the first attempts have been made to control plant growth through modulation of cell-cycle genes. These results suggest that there is significant potential to control plant growth and architecture through manipulation of cell division rates. However, a full realisation of the promise of such strategies will probably require a much greater understanding of cell division control and how its upstream regulation is co-ordinated by spatial relationships between cells and by environmental signals.

Cell Cycle↗
PubMed2000

Triggering the cell cycle in plants.

In essence, the mitotic cell cycle in eukaryotes involves the duplication and separation of chromosomes, coupled to the process of dividing one cell into two. Cytokinesis is therefore the culmination of a series of events that were triggered during G1 phase, and brings the daughter cells back to the starting position in G1 for another possible round of division. In all eukaryotes, progression through the cell cycle is controlled by cyclin-dependent kinases that bind to positive regulators called cyclins. This review explores some of the pathways that trigger the plant cell cycle, with emphasis on the G1 phase. Examples include signalling pathways involving glutathione and cellular redox potential, the possible existence of a G1 DNA-damage checkpoint, and the plant hormones auxin and cytokinin. Progress in understanding the link between cell proliferation, cell differentiation and the cell-cycle machinery in a developmental context is discussed.

G1 Phase↗
PubMed2000

Complications and cost associated with parenteral nutrition delivered to hospitalized patients through either subclavian or peripherally-inserted central catheters.

BACKGROUND AND AIMS: Total parenteral nutrition (TPN) is typically delivered through catheters inserted into the superior vena cava (SVC) via a subclavian or internal jugular vein approach. A peripherally-inserted central venous catheter (PICC), utilizing a cephalic or basilic venous approach, may provide a safe alternative to the standard catheter approach and, because non-physician providers can insert the PICC, may introduce a potential cost-savings to health care institutions. We sought to determine if PICC lines are safer and more cost-effective than the standard central venous catheter approach for hospitalized patients who require TPN. METHODS: One hundred and two hospitalized patients (age range, 18-88 years) who required TPN were prospectively randomized to receive therapy via a centrally-inserted subclavian catheter (n=51) or a peripherally-inserted PICC line (n=51). The primary end-point was the development of a complication requiring catheter removal. Other end-points included catheter infection and thrombophlebitis. Cost associated with insertion and maintenance of each catheter was also studied. RESULTS: Complication-free delivery rate (without the need to remove or replace the catheter) was 67% for subclavian catheters and 46% for PICC lines (P<0.05). The overall infection rate was 4.9 per 1000 catheter days and was similar for each catheter type (P=0.68). PICC lines were associated with higher rates of clinically-evident thrombophlebitis (P<0.01), difficult insertion attempts (P<0.05), and malposition on insertion (P<0.05). No catheter complications resulted in significant long-term morbity or mortality. No significant difference was noted between the two catheter types in terms of aborted insertion attempts (P=0.18), dislodgement (P=0.12), or line occlusion (P=0.25). After standardizing costs for each hospital, the direct institutional costs for insertion and maintenance of PICC lines (US$22.32+/-2.74 per day) was greater than that for subclavian lines (US$16.20+/-2.96 per day;P<0.05). CONCLUSION: PICC catheters have higher thrombophlebitis rates and are more difficult to insert into certain patients when compared to the standard subclavian approach for central venous access in hospitalized patients who require TPN. Because of this, PICCs may be less cost-effective than currently believed because of the difficulty in inserting and maintaining the catheter.

Adolescent↗
PubMed2000

Effects of a program of intervention on parental distress following infant death.

A longitudinal study of 144 parents (65 fathers, 79 mothers) was conducted to evaluate the effectiveness of a program of intervention in relieving the psychological distress of parents affected by infant death. Participants were assessed in terms of their psychiatric disturbance, depression, anxiety, physical symptoms, dyadic adjustment, and coping strategies. The experimental group (n = 84) was offered an intervention program comprising the use of specially designed resources and contact with a trained grief worker. A control group (n = 60) was given routine community care. Parental reactions were assessed at four to six weeks postloss (prior to the implementation of the intervention program), at six months postloss, and at 15 months postloss. A series of multivariate analyses of variance revealed that the intervention was effective in reducing the distress of parents, particularly those assessed prior to the intervention as being at high-risk of developing mourning difficulties. Effects of the intervention were noted in terms of parents' overall psychiatric disturbance, marital quality, and paternal coping strategies.

Adaptation, Psychological↗
PubMed2000

Endpoints of resuscitation of critically injured patients: normal or supranormal? A prospective randomized trial.

OBJECTIVE: To evaluate the effect of early optimization in the survival of severely injured patients. SUMMARY BACKGROUND DATA: It is unclear whether supranormal ("optimal") hemodynamic values should serve as endpoints of resuscitation or simply as markers of the physiologic reserve of critically injured patients. The failure of optimization to produce improved survival in some randomized controlled trials may be associated with delays in starting the attempt to reach optimal goals. There are limited controlled data on trauma patients. METHODS: Seventy-five consecutive severely injured patients with shock resulting from bleeding and without major intracranial or spinal cord trauma were randomized to resuscitation, starting immediately after admission, to either normal values of systolic blood pressure, urine output, base deficit, hemoglobin, and cardiac index (control group, 35 patients) or optimal values (cardiac index >4.5 L/min/m2, ratio of transcutaneous oxygen tension to fractional inspired oxygen >200, oxygen delivery index >600 mL/min/m2, and oxygen consumption index >170 mL/min/m2; optimal group, 40 patients). Initial cardiac output monitoring was done noninvasively by bioimpedance and, subsequently, invasively by thermodilution. Crystalloids, colloids, blood, inotropes, and vasopressors were used by predetermined algorithms. RESULTS: Optimal values were reached intentionally by 70% of the optimal patients and spontaneously by 40% of the control patients. There was no difference in rates of death (15% optimal vs. 11% control), organ failure, sepsis, or the length of intensive care unit or hospital stay between the two groups. Patients from both groups who achieved optimal values had better outcomes than patients who did not. The death rate was 0% among patients who achieved optimal values compared with 30% among patients who did not. Age younger than 40 years was the only independent predictive factor of the ability to reach optimal values. CONCLUSIONS: Severely injured patients who can achieve optimal hemodynamic values are more likely to survive than those who cannot, regardless of the resuscitation technique. In this study, attempts at early optimization did not improve the outcome of the examined subgroup of severely injured patients.

Adult↗
PubMed2000

Prevention of venous thromboembolism after injury: an evidence-based report--part I: analysis of risk factors and evaluation of the role of vena caval filters.

BACKGROUND: Trauma surgeons use a variety of methods to prevent venous thromboembolism (VT). The rationale for their use frequently is based on conclusions from research on nontrauma populations. Existing recommendations are based on expert opinion and consensus statements rather than systematic analysis of the existing literature and synthesis of available data. The objective is to produce an evidence-based report on the methods of prevention of VT after injury. METHODS: A panel of 17 national authorities from the academic, private, and managed care sectors helped design and review the project. We searched three electronic databases (MEDLINE, EM-BASE, and Cochrane Controlled Trial Register) to identify articles relevant to four key questions: methods of prophylaxis, methods of screening, risk factors for VT, and the role of vena caval filters. The initial 4,093 titles yielded 73 articles for meta-analysis. A random-effects model was used for all pooled results. Study quality was evaluated by previously published quality scores. In this article (part I), we report on the question ranked by the experts as the most important, i.e., Which is the best method to prevent VT?, and also on the incidence of deep venous thrombosis and pulmonary embolism in trauma patients. RESULTS: The incidence of deep venous thrombosis and pulmonary embolism reported in different studies varies widely. The pooled rates are 11.8% for deep venous thrombosis and 1.5% for pulmonary embolism. Only a few randomized controlled trials have evaluated the methods of VT prophylaxis among trauma patients, and combining their data is difficult because of different designs and preventive methods used. The quality of most studies is low. Meta-analysis shows no evidence that low-dose heparin, mechanical prophylaxis, or low-molecular-weight heparin are more effective than no prophylaxis or each other. However, the 95% confidence intervals of many of the comparisons are wide; therefore, a clinically important difference may exist. CONCLUSION: The trauma literature on VT prophylaxis provides inconsistent data. There is no evidence that any existing method of VT prophylaxis is clearly superior to the other methods or even to no prophylaxis. Our results cast serious doubt on the existing policies on VT prophylaxis, and we call for a large, high-quality, multicenter trial that can provide definitive answers.

Evidence-Based Medicine↗
PubMed2000

Prevention of venous thromboembolism after injury: an evidence-based report--part II: analysis of risk factors and evaluation of the role of vena caval filters.

OBJECTIVE: In part II, we describe the results of the literature search and data analysis concerning risk factors for venous thromboembolism and the role of vena caval filters (VCF) in preventing pulmonary embolism. METHODS: The methodology used in part I was used in part II. RESULTS: Spinal fractures and spinal-cord injuries increase the risk for development of deep venous thrombosis (DVT) by twofold and threefold, respectively. Patients with DVT were an average of 9 years older than patients without DVT. No specific age cut-off point for increased risk could be established because data could not be combined across studies. Patients with prophylactically inserted VCF had a lower incidence of pulmonary embolism (0.2%) compared with concurrently managed patients without VCF (1.5%) or historical controls without VCF (5.8%). These results are reported on uncontrolled studies with observational design. CONCLUSION: Spinal injuries, spinal cord injuries, and age are risk factors for development of DVT. Prophylactic placement of VCF in selected trauma patients may decrease the incidence of pulmonary embolism. Future research with well-designed studies is required to provide definitive answers.

Evidence-Based Medicine↗
PubMed2000

Prehospital intubation in patients with severe head injury.

BACKGROUND: Prehospital intubation and airway control is routinely performed by paramedics in critically injured patients. Despite the advantages provided by this procedure, numerous potential risks exist when this is performed in the field. We reviewed the outcome of patients with severe head injury, to determine whether prehospital intubation is associated with an improved outcome. METHODS: A retrospective review of registry data of patients admitted to an urban trauma center with severe head injury (field Glasgow Coma Scale score of < or =8 and head Abbreviated Injury Scale score of > or =3) was performed. Patients were stratified by methods of airway control performed by prehospital personnel: not intubated, intubated, or unsuccessful intubation. Mortality was determined for each group. To control for significant variables between these populations, matching and multivariate analysis were performed. RESULTS: Patients requiring prehospital intubation or in whom intubation was attempted had an increased mortality (81% and 77%, respectively) when compared with nonintubated patients (43%). The mortality for patients who had prehospital intubation performed did not demonstrate an improved survival using matching. In fact, intubated patients had a significantly higher relative risk (RR) of mortality when compared with nonintubation (RR = 1.74,p < 0.001) and unsuccessful intubation patients (RR = 1.53, p = 0.008) CONCLUSION: For patients with severe head injury, prehospital intubation did not demonstrate an improvement in survival. Further prospective randomized trials are necessary to confirm these results.

Adolescent↗
PubMed2000

The expression of D-cyclin genes defines distinct developmental zones in snapdragon apical meristems and is locally regulated by the Cycloidea gene.

Three D-cyclin genes are expressed in the apical meristems of snapdragon (Antirrhinum majus). The cyclin D1 and D3b genes are expressed throughout meristems, whereas cyclin D3a is restricted to the peripheral region of the meristem, especially the organ primordia. During floral development, cyclin D3b expression is: (a) locally modulated in the cells immediately surrounding the base of organ primordia, defining a zone between lateral organs that may act as a developmental boundary; (b) locally modulated in the ventral petals during petal folding; and (c) is specifically repressed in the dorsal stamen by the cycloidea gene. Expression of both cyclin D3 genes is reduced prior to the cessation of cell cycle activity, as judged by histone H4 expression. Expression of all three D-cyclin genes is modulated by factors that regulate plant growth, particularly sucrose and cytokinin. These observations may provide a molecular basis for understanding the local regulation of cell proliferation during plant growth and development.

Amino Acid Sequence↗
PubMed2000

Serologic testing for celiac disease in the United States: results of a multilaboratory comparison study.

The aim of this study was to compare the efficiencies of six reference laboratories for serologic testing for celiac disease. Serum from 20 patients with untreated celiac disease and from 20 controls was thawed, divided, and distributed to each participating laboratory, which performed endomysial antibody tests. Five laboratories also performed antigliadin antibody tests. Sensitivity for endomysial antibody immunoglobulin A (IgA) varied from 57 to 90%. In all laboratories, the specificity for celiac disease was 100%. The sensitivity and specificity for both IgA and IgG antigliadin antibody varied significantly. When results from all three tests were combined in each laboratory, sensitivity was 90 to 100%. The specificity for endomysial antibody was 100% in the laboratories. Sensitivity was less than reported previously. Standardization of these tests is needed in the United States.

Celiac Disease↗
PubMed2000

Sugar control of the plant cell cycle: differential regulation of Arabidopsis D-type cyclin gene expression.

In most plants, sucrose is the major transported carbon source. Carbon source availability in the form of sucrose is likely to be a major determinant of cell division, and mechanisms must exist for sensing sugar levels and mediating appropriate control of the cell cycle. We show that sugar availability plays a major role during the G(1) phase by controlling the expression of CycD cyclins in Arabidopsis. CycD2 mRNA levels increase within 30 min of the addition of sucrose; CycD3 is induced after 4 h. This corresponds to induction of CycD2 expression early in G(1) and CycD3 expression in late G(1) near the S-phase boundary. CycD2 and CycD3 induction is independent both of progression to a specific point in the cell cycle and of protein synthesis. Protein kinase activity of CycD2- and CycD3-containing cyclin-dependent kinases is consistent with the observed regulation of their mRNA levels. CycD2 and CycD3 therefore act as direct mediators of the presence of sugar in cell cycle commitment. CycD3, but not CycD2, expression responds to hormones, for which we show that the presence of sugars is required. Finally, protein phosphatases are shown to be involved in regulating CycD2 and CycD3 induction. We propose that control of CycD2 and CycD3 by sucrose forms part of cell cycle control in response to cellular carbohydrate status.

Arabidopsis↗
PubMed2000

Role of cGMP as a mediator of nerve-induced motor functions of the opossum esophagus.

Stimulation of esophageal nerves produces biphasic relaxation of the lower esophageal sphincter (LES) and an off response of circular esophageal muscle. Previously, we proposed that cGMP mediates nerve-induced hyperpolarization of circular LES muscle but not LES relaxation. These experiments explore whether cGMP mediates LES relaxation or the off response. Strips of muscle from the opossum esophagus and LES were connected to force-displacement transducers, placed in tissue baths containing oxygenated Krebs solution at 37 degrees C, and stimulated by an electrical field. 1H-[1,2, 4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), a selective inhibitor of guanylyl cyclase, antagonized the off response, shortened its latency, and blocked the first phase of LES relaxation. ODQ also antagonized LES relaxation by exogenous nitric oxide (NO) but not relaxations by vasoactive intestinal polypeptide (VIP). Part of the nerve-induced LES relaxation and the off response appear to be mediated by the second messenger cGMP. These studies indicate that VIP-induced LES relaxation is not mediated by cGMP and therefore do not support the hypothesis that VIP produces LES relaxation by causing the generation of NO.

Animals↗
PubMed2000

New perspectives in gastric acid suppression: genetic polymorphisms predict the efficacy of proton pump inhibitors.

Proton pump inhibitors are highly effective in the management of acid-peptic diseases. These drugs potently inhibit acid secretion from gastric parietal cells by irreversibly inhibiting activity of the H(+), K(+) ATPase (proton pump). Early studies of the pharmacokinetics of proton pump inhibitors demonstrated considerable variation in drug clearance rates among patients and healthy volunteers. This variation was also reflected in a wide range of the efficacy of acid suppression by standard doses of proton pump inhibitors among study subjects; those with slower clearance and higher drug concentrations experienced superior acid suppression. Proton pump inhibitors are predominantly inactivated by the 2C19 isoform of the hepatic cytochrome P450 mixed function oxidase system. The cytochrome P450 2C19 gene is polymorphic, with three known inactivating mutations. Individuals with one or two mutant cytochrome P450 2C19 alleles metabolize proton pump inhibitors more slowly than those with two wild-type alleles and experience higher drug levels. An individual's cytochrome P450 2C19 genotype predicts the degree of acid suppression in response to a standard dose of a proton pump inhibitor. Emerging data suggests that the clinical effectiveness of proton pump inhibitors in the treatment of acid-peptic diseases may also be dependent on cytochrome P450 2C19 genotype.

Cytochrome P-450 Enzyme System↗
PubMed2000

Controlled induction of GUS marked clonal sectors in Arabidopsis.

Stably transformed Arabidopsis lines in which GUS marked cell clones are readily produced in response to heat-shock have been established and characterized. Control of GUS activation is achieved by heat-shock-induced FLP recombinase activity which "switches on" expression of a GUS marker gene previously held transcriptionally silent. To obtain efficient GUS sectoring, single insert Arabidopsis lines carrying FLP recombinase under the control of a heat-shock-inducible promoter and an FLP-activatable GUS construct were generated. Analysis of GUS sectoring in lines hemizygous and homozygous for both inserts was conducted after various regimes of heat-shock were given at various developmental stages. It is shown that GUS sectoring events can be efficiently induced in most vegetative, aerial and sexual structures in Arabidopsis. Furthermore, the frequency of sectoring events, sector size and, to some extent, the tissues in which sectors are generated can be readily controlled by choice of the conditions and timing of heat-shock used.

Arabidopsis↗
PubMed2000

Fetal death after trauma in pregnancy.

Trauma in pregnancy places the mother and fetus at risk. The objective of this study is to identify risk factors independently associated with acute termination of pregnancy and/or fetal mortality after trauma. The medical and trauma registry records of 80 injured pregnant patients were reviewed. Data were collected and then analyzed by univariate and multivariate analysis. Three patients died (3.7%), 23 had the pregnancy acutely terminated (30%), and 14 suffered fetal death (17.5%). The only independent risk factors for fetal mortality were an Injury Severity Score (ISS) > or =9 and a nonviable pregnancy (<23 weeks). The combination of both risk factors increased the likelihood of fetal mortality by fivefold over that of patients without either risk factor. Maternal hemodynamic parameters did not predict fetal loss. Two patients lost their fetuses despite insignificant trauma (ISS = 1) and normal hemodynamic parameters, whereas eight delivered normal babies despite major trauma (ISS > or = 16). Hemodynamic stability on admission does not predict fetal mortality. Although the presence of moderate to severe injuries (ISS > or = 9) increases the likelihood of fetal mortality, this complication may occur even with insignificant trauma. Close maternal and fetal monitoring is justified, regardless of maternal hemodynamic presentation or severity of injury.

Abbreviated Injury Scale↗