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Biomedical subjects

G Ramsay

Publications and source records attributed to G Ramsay.

At least 19 recordsLinked to original sources

Risk prediction in patients presenting with suspected cardiac pain: the GRACE and TIMI risk scores versus clinical evaluation.

BACKGROUND: Identifying which patients presenting with undifferentiated chest pain are at risk of major cardiac events is a major clinical challenge. Clinical evaluation may lack sufficient precision, leading to unnecessary admission or inappropriate discharge. It is uncertain whether risk scores derived from ACS populations apply to unselected patients with chest pain. AIM: To determine the predictive accuracies of the GRACE risk score, the TIMI risk score and clinical evaluation in unselected patients with suspected cardiac pain. DESIGN: Prospective observational study. METHODS: We recruited 347 sequential patients with suspected cardiac pain presenting to a large teaching hospital. The main outcome measures were death, non-fatal myocardial infarction and emergency revascularization, in hospital and at 3 months. Receiver operating characteristic (ROC) curves were plotted for TIMI and GRACE risk scores and clinical evaluation. RESULTS: Overall 54 patients (15.6%) experienced a major cardiac event (16 deaths, seven myocardial infarctions (MIs), one emergency revascularization) or emergency re-admission (n=30) within 3 months. Both GRACE (p<0.001) and TIMI scores (p<0.001) predicted death/MI/revascularization (and the composite including re-admission), but the GRACE score was superior to the TIMI score for predicting major cardiac events (z=2.05), and both scores were superior to clinical evaluation (ROC areas 0.82, 0.74 and 0.55 respectively). The GRACE score predicted an ACS discharge diagnosis (p<0.001) and duration of hospital stay (p<0.001). DISCUSSION: In unselected patients presenting with suspected cardiac pain, the GRACE risk score is superior to the TIMI risk score in predicting major cardiac events, and both risk scores are superior to using ECG and troponin findings at presentation.

Aged↗

Transgenic peas (Pisum sativum) expressing polygalacturonase inhibiting protein from raspberry (Rubus idaeus) and stilbene synthase from grape (Vitis vinifera).

The pea (Pisum sativum L.) varieties Baroness (United Kingdome) and Baccara (France) were transformed via Agrobacterium tumefaciens-mediated gene transfer with pGPTV binary vectors containing the bar gene in combination with two different antifungal genes coding for polygalacturonase-inhibiting protein (PGIP) from raspberry (Rubus idaeus L.) driven by a double 35S promoter, or the stilbene synthase (Vst1) from grape (Vitis vinifera L.) driven by its own elicitor-inducible promoter. Transgenic lines were established and transgenes combined via conventional crossing. Resveratrol, produced by Vst1 transgenic plants, was detected using HPLC and the PGIP expression was determined in functional inhibition assays against fungal polygalacturonases. Stable inheritance of the antifungal genes in the transgenic plants was demonstrated.

Acyltransferases↗

An efficient transformation system for chickpea (Cicer arietinum L.).

A reproducible and efficient transformation method was developed for Desi and Kabuli chickpeas (Cicer arietinum L.) using germinated seedlings as sources of explants. Slices derived from plumules were the most efficient at generating transformed shoots. The AGL1 Agrobacterium-treated explants were first incubated on thidiazuron-containing media, then selected using phosphinothricin. Resistant shoots were successfully transferred to soil either by grafting or in vitro rooting. In experiments each taking 4-9 months, a total of 41 confirmed transformed lines were created using embryo axis slices as source explants, giving a transformation frequency of 5.1%. Southern analysis and histochemical and leaf painting assays demonstrated integration and expression of the transgenes in the initial transformants and two generations of progeny.

Cicer↗

Successful treatment of severe bleeding with recombinant factor VIIa after kidney transplantation.

Recombinant factor VIIa (rFVIIa, NovoSeven) has been registered for the treatment of bleeding episodes in patients with inherited or acquired hemophilia A or B with inhibitors. Furthermore, rFVIIa has been used successfully for the treatment of bleeding in patients with thrombocytopenia, and acquired and congenital platelet dysfunction. The definite spectrum of indications for rFVIIa has not yet been established. We describe a case of severe intra-abdominal bleeding 3 days after non-heart beating kidney transplantation in a patient with severe coronary artery disease in which rFVIIa (a single intravenous bolus injection 70 microg/kg bodyweight) was successfully used. No thrombotic complications occurred. This report demonstrates that rFVIIa might be safe and effective after recent renal transplantation.

Factor VIIa↗

Problems in interhospital pediatric intensive care transport in The Netherlands: results from a survey of general pediatricians.

OBJECTIVE: Interhospital pediatric intensive care transport accompanied by non-trained specialists usually occurs with inadequate equipment and has been associated with high incidence of complications. These facts have serious consequences for patients but also can be very disconcerting for specialists. This survey was undertaken to gain insight into the problems encountered in organizing pediatric intensive care transport in The Netherlands to measure the specialist's satisfaction or dissatisfaction with the current state of affairs in the organization of such transports, and additional workload and feelings of insecurity experienced during self-organized transports. DESIGN: Survey, retrospective. SETTING: A postal questionnaire sent to all pediatricians of community hospitals in The Netherlands. METHODS: Results of direct questioning are given as discrete frequencies. After factor and reliability analysis 5-point Likert scale items are summed up in scale constructions. Relationships between scales are examined in regression analysis. RESULTS: Pediatricians appear to be satisfied with current specialist retrieval teams if these teams are available in their region, and highly dissatisfied if not available. Many nontrained specialists consider these transports burdening tasks with a high workload, and they feel insecure during these transports, especially if they report lack of knowledge of the transport equipment. CONCLUSIONS: The need for pediatric specialist retrieval teams in The Netherlands is seen not only in the insufficient level of care delivered by accompanying nontrained specialists and the reported high incidence of complications as shown in the literature but also in the dissatisfaction and high stress of these specialists.

Child↗

X-ray observations of accreting white-dwarf systems.

Accretion in white-dwarf binary systems can occur through discs, accretion columns or a combination of these, depending on the magnetic field of the white dwarf. Recent high-quality X-ray observations with the XMM-Newton and Chandra observatories have significantly advanced our understanding of the physics of the accretion process, and place severe tests on our existing models. There have been some surprises, such as the strong dependence of atmospheric heating on accretion rate. However, we believe that we are now confident that we understand in general the physical processes in the accretion region, although some complicating factors, such as absorption, remain. We also discuss new developments in ultra-short-period white-dwarf binary systems.

Journal Article↗

Hypoxia induces aortic hypertrophic growth, left ventricular dysfunction, and sympathetic hyperinnervation of peripheral arteries in the chick embryo.

BACKGROUND: Low birth weight is associated with an increased incidence of cardiovascular diseases, including hypertension, later in life. This suggests that antenatal insults program for fetal adaptations of the circulatory system. In the present study, we evaluated the effects of mild hypoxia on cardiac function, blood pressure control, and arterial structure and function in near-term chick embryos. METHODS AND RESULTS: Chick embryos were incubated under normoxic (21% O2) or hypoxic (15% O2) conditions and evaluated at incubation day 19 by use of histological techniques, isolated heart preparations, and in vivo measurements of sympathetic arterial tone and systemic hemodynamics. Chronic hypoxia caused a 33% increase in mortality and an 11% reduction in body weight in surviving embryos. The lumen of the ascending aorta in hypoxic embryos was 23% smaller. Left ventricular systolic pressure was 22% lower, and heart weight/body weight ratio was 14% higher. In resistance arteries of hypoxic embryos, in vivo baseline tone was 23% higher, norepinephrine sensitivity was similar, and norepinephrine release from sympathetic nerves increased 2-fold, indicating sympathetic hyperinnervation. Mean arterial pressure and heart rate were similar under resting conditions, but chronically hypoxic embryos failed to maintain blood pressure during acute stress. CONCLUSIONS: This study indicates that mild hypoxia during embryonic development induces alterations in cardiac and vascular function and structure and affects hemodynamic regulation. These findings reveal that antenatal insults have profound effects on the control and design of the circulatory system that are already established at birth and may program for hypertension and heart failure at a later age.

Animals↗

Effects of experimental lower-limb ischaemia-reperfusion injury on the mesenteric microcirculation.

BACKGROUND: Ischaemia-reperfusion (I-R) of the leg is associated with functional and structural changes in the intestine. This study assessed whether acute hind-limb I-R in rats induced a reduction in perfusion and/or signs of an inflammatory response in the intestine. METHODS: Rats were subjected to 2 h of unilateral hind-limb ischaemia followed by 2 h of reperfusion (I-R group, n = 9) or to a sham procedure (control group, n = 9). Mesenteric microvascular diameters, red blood cell velocity, blood flow and leucocyte-vessel wall interactions during reperfusion were measured using intravital microscopy. RESULTS: Blood pressure and heart rate decreased from 30 min of reperfusion onwards in the I-R group compared with controls. From 15 min after the start of reperfusion, mesenteric arteriolar and venular red blood cell velocity and blood flow decreased by 40-50 per cent. Microvascular diameters and leucocyte-vessel wall interactions did not change. CONCLUSION: Restoration of blood flow to an acutely ischaemic hind limb led to a significant decline in the splanchnic microcirculatory blood flow. There were, however, no signs of an early inflammatory response in the gut.

Animals↗

Increased hepatosplanchnic inflammation precedes the development of organ dysfunction after elective high-risk surgery.

This study investigated the relationship of the hepatosplanchnic production and uptake of inflammatory mediators, hepatosplanchnic perfusion, and outcome during major abdominal surgery to evaluate the hypothesis that regional production of inflammatory mediators precedes the development of hepatic dysfunction. This retrospective analysis of data and blood samples collected during a randomized controlled clinical trial included high-risk surgical patients undergoing major abdominal surgery in a 24-bed university-afilliated intensive care unit. Patients were divided into a subgroup that developed hepatic dysfunction (HD+) postoperatively and a subgroup without hepatic dysfunction (HD-). Hepatic vein and arterial plasma levels of IL-6, IL-8, s-E-selectin, s-ICAM-1, and the TNF-receptors 55 and 75 were measured, and the flux was calculated by multiplying the difference in hepatic vein minus arterial levels of the mediators by the hepatosplanchnic flow. Systemic (thermodilution) and total hepatosplanchnic blood flow (using indocyanine green [ICG]-dilution method) and gastric intramucosal pH (pHi) were assessed preoperatively, 4, 24, and 36 h postoperatively. Of a total of 26 patients, 6 patients developed hepatic dysfunction after their abdominal surgery (mean 6 days postoperatively). The number of sepsis-related deaths and postoperative days on the ventilator were significantly higher in this group. A higher production of IL-8, TNF-receptor-75 and 55 in the hepatosplanchnic area in the HD+ subgroups was found, which preceded the development of organ dysfunction (P = 0.04, P = 0.02, and P = 0.02, respectively). Moreover, the uptake of s-ICAM-1 was significantly increased in this subgroup. Furthermore, total hepatosplanchnic blood flow was significantly higher and pHi was significantly lower in the HD+ group, whereas global hemodynamic data were similar in the two subgroups. In conclusion, the development of postoperative organ dysfunction is preceded by an increased regional inflammatory response, indicated by an increased soluble TNF-receptor shedding and IL-8 production from the hepatosplanchnic area together with an increased uptake of s-ICAM-1. Moreover, an increased total hepatosplanchnic blood flow with intramucosal acidosis was associated with this regional inflammatory response.

Aged↗

The effect of metal salt treatment on the photoluminescence of DFO-treated fingerprints.

Ninhydrin developed fingerprints can be enhanced by treatment with a zinc or cadmium salt. The resulting fingerprint luminescence has been attributed to the induced coplanarity of the bicyclic indanedione rings of Ruhemann's purple due to complexation with the metal ions. This paper explores whether this effect also occurs in the 1,8-diaza-9-fluorenone (DFO)-amino acid adduct (1), formed from the reaction of DFO with amino acids. Molecular modeling studies of (1) indicate a relatively small out-of-plane angle of 24 degrees. 1H NMR studies indicate (1) is asymmetric about the C2 axis in contrast to what has been previously reported. Little, if any, enhancement of luminescence was observed with Zn, Cd, Ru or Eu treated DFO developed latent fingerprints. This lack of enhancement was also borne out by solution luminescence studies. Given this lack of enhancement of luminescence, solutions of (1) and the four metal ions above were analyzed by electrospray mass spectrometry (ESMS). This indicated the formation of predominantly 1:1 complexes of (1) with both Zn and Cd, and the 2:1 complex with ruthenium. No evidence of a Eu complex was found by ESMS.

Amino Acids↗

Comparative clinical trial of progressive dilatational and forceps dilatational tracheostomy.

OBJECTIVE: To compare the safety and early complications of progressive dilatational tracheostomy (PDT) and forceps dilatational tracheostomy (FDT). DESIGN: Prospective randomized trial. SETTING: Three-centre university and public teaching hospitals. PATIENTS: One hundred and twenty-seven consecutive patients were randomized to undergo PDT or FDT. RESULTS: The duration of the procedure was 7.0 +/- 3.5 min in the PDT group and 6.4 +/- 4.9 min in the FDT group, which was not significantly different. Intraprocedural complications occurred in 14 % with PDT and 31% with FDT (p = 0.03), and were usually minor. Difficult or false insertion of the cannula in eight patients after FDTwas the most common complication. CONCLUSIONS: Both percutaneous tracheostomy techniques are safe. The early complication rate of PDT appeared to be lower than FDT, but the early complication rate of FDT may be decreased significantly with small modifications to the set.

Aged↗

The development of ventilator-associated pneumonia does not change aspects of mechanical ventilation.

OBJECTIVE: To evaluate whether the development of ventilator-associated pneumonia (VAP) is associated with changes in ventilation parameters. DESIGN: Matched case-control study. SETTING: Mixed intensive care unit of a university hospital. PATIENTS: From a large database we selected 33 patients with VAP, diagnosed with quantitative cultures of bronchoscopically obtained specimens. In addition, 33 other mechanically ventilated patients who did not develop VAP were selected (controls). Patients with VAP and controls were matched on seven variables representing severity of illness: duration of ventilation until matching, diagnosis on admission, renal function, liver function, preceding infection, preceding surgery and immunosuppressive therapy. Each patient with VAP was matched to a single control. Variables regarding type and mode of ventilation and interpretation of chest radiographs were not included in the matching procedure. MEASUREMENTS AND RESULTS: Characteristics of mechanical ventilation (mode of ventilation, tidal volume, expired minute ventilation, peak airway pressures, mean airway pressures, level of positive end-expiratory pressure, arterial oxygen tension(PaO2)/fractional inspired oxygen (FIO2) ratio), were compared on the day of diagnosis of VAP (or matching for controls) and 2 and 4 days before. Although there was a significant difference in PaO2/FIO2 ratios between cases and controls on the day of diagnosis of VAP, the change in PaO2/FIO2 ratios during the days of study were not statistically different between patients developing VAP and controls. No significant differences were found for any of the other variables of ventilation at any of the three time points studied, nor were there significant differences in changes of these parameters within individual patients. CONCLUSIONS: Characteristics and parameters of mechanical ventilation are not influenced by the development of VAP. It is, therefore, unlikely that these variables are useful in the diagnostic work-up of VAP.

Case-Control Studies↗

Microcirculatory effects of experimental acute limb ischaemia-reperfusion.

BACKGROUND: The object of this study was to develop an animal model in which changes in microvascular haemodynamics and leucocyte-vessel wall interactions due to acute limb ischaemia-reperfusion (I/R) can be measured in the skin. Furthermore, it was investigated whether these changes are related to local muscle injury. METHODS: Male Lewis rats were subjected to unilateral limb ischaemia for 1 h (n = 8) or 2 h (n = 8) by cuff inflation, or to a sham protocol (n = 6). Intravital video microscopic measurements of leucocyte-vessel wall interactions, venular diameter, red blood cell velocity and reduced velocity (which is proportional to wall shear rate) were performed in skin venules before ischaemia and at 0.5, 1, 2, 3 and 4 h after the start of reperfusion. Oedema and leucocyte infiltration of ischaemic/reperfused skeletal muscle were quantified histologically. RESULTS: In skin venules, both 1 and 2 h of ischaemia induced a significant increase in leucocyte rolling (six and five times baseline, respectively; P < 0.05) and adherence during reperfusion (eight and four times baseline; P < 0.05). No significant increase in muscular leucocyte infiltration was detected. After an initial hyperaemic response of 180 per cent of baseline values (P < 0.05), blood flow decreased to about 60 per cent after 4 h of reperfusion in skin venules of both experimental groups. I/R induced tibial muscle oedema, the severity of which depended on the ischaemic interval (wet to dry ratio: control, 4.0; 1 h, 4.5 (P not significant); 2 h, 5.8 (P < 0.05)). CONCLUSION: A non-invasive animal model was developed that enables investigation of the consequences of acute limb I/R.

Animals↗

Resolution of infectious parameters after antimicrobial therapy in patients with ventilator-associated pneumonia.

Although recommended durations of antimicrobial therapy for ventilator-associated pneumonia (VAP) range from 7 to 21 d, these are not based on prospective studies and little is known about the resolution of symptoms after start of antibiotics. Resolution of these symptoms was investigated in 27 patients. VAP was diagnosed on clinical, radiographic, and microbiological criteria, including quantitative cultures of bronchoalveolar lavage. All patients received appropriate antibiotic therapy. Highest temperatures, leukocyte counts, Pa(O(2))/FI(O(2)) ratios, and semiquantitative cultures of endotracheal aspirates were recorded from start of therapy until Day 14. Resolution was defined as the first day that these parameters fulfilled the following definition: temperature < or = 38 degrees C, leukocytes < or = 10 x 10(9)/L, Pa(O(2))/FI(O(2)) ratio > or = 25 kPa, and no or +1 of bacterial growth of etiologic pathogens in cultures of endotracheal aspirate. VAP was caused by Enterobacteriaceae (n = 14), P. aeruginosa (n = 7), S. aureus (n = 6), H. influenzae (n = 3), and S. pneumoniae (n = 1). H. influenzae and S. pneumoniae were eradicated from tracheal aspirates, whereas Enterobacteriaceae, S. aureus, and P. aeruginosa persisted, despite in vitro susceptibility to antibiotics administered. Significant improvements were observed for all clinical parameters, most apparently within the first 6 d after start of antibiotics. Newly acquired colonization, especially with P. aeruginosa and Enterobacteriaceae, occurred in the second week of therapy. Six patients developed a recurrent episode of VAP, four of them with P. aeruginosa. Clinical responses to therapy for VAP occur within the first 6 d of therapy, endotracheal colonization with Gram-negative bacteria persists despite susceptibility to therapy, and acquired colonization usually occurs in the second week of therapy and frequently precedes a recurrent episode.

Adult↗

Pre-operative tonometry is predictive for mortality and morbidity in high-risk surgical patients.

OBJECTIVE: To determine whether a) pre-operative measurement of gastric intramucosal pHi is predictive for mortality and morbidity in high-risk surgical patients and b) peri-operative improvement of global oxygen delivery (DO2) with fluids and dopexamine leads to increased gastric pHi and c) either improved global perfusion or improved splanchnic perfusion is related to the prevention of multiple organ failure (MOF). DESIGN: Retrospective analysis of a double-blind, placebo-controlled, randomised study. SETTING: General intensive care units from 14 hospitals. PATIENTS: Two hundred eighty-six high-risk surgical patients. INTERVENTIONS: Swan-Ganz and tonometer catheter placement; patients were stabilised pre-operatively using fluids, blood and/or oxygen to preset goals before receiving placebo or two doses of dopexamine (0.5 or 2.0 microg.kg.min) peri-operatively. MEASUREMENTS AND RESULTS: Haemodynamic assessment (including DO2 and oxygen consumption (VO2)) was performed together with measurement of gastric mucosal pHi pre-operatively and directly, 2, 6, 12, 24 and 36 h post-operatively. Retrospectively, patients were divided pre-operatively into two sub-groups based on the optimal cut-off value for mortality of the first pHi measurement after induction of anaesthesia as calculated by a receiver operator characteristic (ROC) curve analysis --low pHi group (< 7.35) and normal pHi (> or =7.35). Mortality in the low pHi, was higher than in the normal pHi, group (16.8 vs 2.3%; p = 0.0001). In the normal pHi group dopexamine, which was given prior to the first pHi measurement, had no effect on pHi, while DO2 increased significantly. In this group MOF score and number of patients with MOF remained similar for the treatment sub-groups. In the low pHi group gastric pHi increased significantly during dopexamine infusion (p = 0.008), despite the lack of an increase in DO2 and VO2. In this group the MOF score and the number of patients developing MOF decreased significantly with the use of dopexamine (p = 0.04). In both groups bicarbonate levels remained similar for the treatment subgroups. CONCLUSIONS: In high-risk surgical patients pre-operative measurement of pHi was predictive for mortality. The peri-operative response of pHi to dopexamine seemed to be dependent on pre-operative gastric pHi.

Analysis of Variance↗