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Biomedical subjects

S Lawson

Publications and source records attributed to S Lawson.

At least 37 records · Page 2Linked to original sources
PubMed1999

Use of idarubicin in pre-transplant conditioning in children with high-risk acute leukaemia.

The major cause of treatment failure following allogeneic bone marrow transplantation for acute leukaemia is disease relapse. In an attempt to reduce post- transplant relapse in 33 children with high-risk acute leukaemia who received a related or unrelated bone marrow transplant, the pre-transplant conditioning regimen was intensified by the addition of idarubicin. Its toxicity and effects on survival were evaluated over a 57-month period. Toxicity, largely gastrointestinal, was increased but acceptable, and there was no specific regimen-related toxicity. Relapse rates were low (24%) in this high risk group, but mortality was increased in those receiving unrelated donor grafts, largely due to sepsis. Idarubicin does appear to have a role to play in the conditioning regimen of patients with high-risk acute leukaemia undergoing BMT, and may reduce relapse rates without increasing transplant-related mortality.

Acute Disease↗
PubMed1999

Trained nurses can obtain satisfactory bone marrow aspirates and trephine biopsies.

AIMS: To assess the feasibility of training nurse practitioners to perform bone marrow aspiration and trephine biopsy, and to compare the quality of these samples with those obtained by medical staff. METHODS: A retrospective audit was undertaken of nurse practitioner and medical staff performance in bone marrow procedures in a busy haematology day unit. RESULTS: Nurse practitioners fared favourably in comparison with medical staff in performing bone marrow trephine biopsies, with mean biopsy lengths of 11 mm and 10.7 mm respectively. However, only 78% of the smears obtained by the nurses were judged technically satisfactory, compared with 91% prepared by doctors. This discrepancy was thought to be due largely to the quality of slide spreading. CONCLUSIONS: With motivated staff and a structured educational and training programme it is possible for nurse practitioners to perform the techniques of bone marrow aspiration and biopsy, and obtain specimens of satisfactory quality, thus improving efficiency of the haematology day unit and increasing quality of patient care.

Biopsy, Needle↗
PubMed1998

Investigating the mechanism and machinery of RNA editing.

RNA editing in trypanosomes produces mature mRNAs by posttranscriptional guide RNA (gRNA)-directed uridylate insertion and deletion. This article describes methods for the study of RNA editing with an emphasis on an in vitro editing system that was used to explore the general mechanism of editing and that can be adapted for more in-depth studies of this intriguing and important process. Methods used to investigate the macromolecular complex that catalyzes RNA editing are also described. This complex is composed of multiple proteins and contains several catalytic activities. It is in the early stages of characterization. The methods described here are intended to assist in its further analysis.

Animals↗
PubMed1998

The role of social deviance and violations in predicting road traffic accidents in a sample of young offenders.

Lawton, Parker, Stradling & Manstead (1997) examined the relationship between mild social deviance (West, Elander & French, 1993 a), driving violations and road traffic accident involvement in a sample of 830 drivers. The relationship between mild social deviance and accident involvement was shown to be partly mediated by propensity to commit driving violations and by factors associated with driver age. The present research replicates and extends this study with a sample of 100 young, male offenders. Self-reports of violations and errors (using the Manchester Driver Behaviour Questionnaire), an extended measures of social deviance, speed preference and accident involvement were collected, together with information about age, annual mileage driven and the type of offence for which the driver was under remand. Factor analysis of the social deviance items yielded two factors: extreme and mild social deviance. Logistic regression was used to investigate the relationship between predictor variables and accident involvement. Both propensity to commit driving violations and extreme social deviance predicted accident involvement in this sample. However, the relationship between extreme social deviance and accident involvement was partly mediated by a tendency to commit driving violations. The implications of the findings for intervention strategies aimed at the prevention of accidents are considered.

Accidents, Traffic↗
PubMed1998

Techniques of paediatric modified ultrafiltration: 1996 survey results.

In September 1996, perfusionists from 50 paediatric open-heart surgery programmes were contacted to identify centres that are currently using the technique of modified ultrafiltration (MUF). Of the 50 centres contacted, 22 (44%) were utilizing the technique. These centres were surveyed on the following: neonatal circuit description, patient entry criteria, MUF circuit description, conduct of MUF, use of extracorporeal safety devices and/or modifications, and technical complications. All 22 centres used roller pumps and membrane oxygenators. In 19 centres, MUF was utilized exclusively in the arteriovenous mode (86%), while two centres (9%) used the venovenous mode and one centre (5%) used both methods. Most (82%) of the 22 MUF centres used a blood cardioplegia system for myocardial preservation. After cardiopulmonary bypass (CPB), these blood cardioplegia systems were often converted for use as MUF circuits in a variety of ways. Other methods of accessing the CPB circuit for MUF included utilizing either a recirculation line or a dedicated port added to the circuit specifically for MUF. Blood flow rates during MUF, pump strategies, haemoconcentrator vacuum levels and endpoints were variable from centre to centre. Technical complications related to MUF were reported by 82% of the surveyed MUF centres. The most common complication, air cavitating into the circuit, was reported by 15 centres. From these data, we propose recommendations on the integration of MUF into CPB circuits, the conduct of perfusion during MUF, and appropriate safety considerations to minimize technical complications.

Cardiac Surgical Procedures↗
PubMed1998

Experimental use of an ultra-low prime neonatal cardiopulmonary bypass circuit utilizing vacuum-assisted venous drainage.

In adult cardiopulmonary bypass surgery, vacuum assisted venous drainage has become a popular technique to augment venous return to the bypass circuit. The application of this technique in neonatal cardiopulmonary bypass surgery could be beneficial to the further miniaturization of neonatal circuitry by coupling radical respositioning of the oxygenator and pump console with decreasing line length. This report communicates the use of an investigational, vacuum assisted venous drainage neonatal circuit that is positioned at patient level utilizing a modified pump console with elevated double head twin roller pumps. The circuit, including the oxygenator, arterial line, venous line, raceway tubing, and a functional level in the venous reservoir has a priming volume of 107 ml. Initial bench and animal tests have demonstrated that this technique may be clinically feasible in CPB applications. With vacuum assisted venous drainage, the goal of asanguinous neonatal cardiac surgery could become a reality. Safety issues must be adequately addressed to ensure that this technique does not impose unacceptable risks.

Adult↗
PubMed1997

Kinetoplastid RNA editing: complexes and catalysts.

RNA editing in kinetoplastids involves post-transcriptional insertion and deletion of uridylates (Us) to produce mature mitochondrial mRNAs with sequences specified by trans acting small guide RNAs. In vitro studies indicate the reaction pathway involves endonucleolytic cleavage of the precursor mRNA at the editing site, uridylate addition or removal at the 3' end of the 5' cleavage product, followed by ligation to the 3' cleavage product. This editing is catalyzed by a macromolecular complex that is in the early stages of characterization. Recent studies have resolved the general mechanism of editing, and show that editing occurs in association with a macromolecular complex.

Animals↗
PubMed1996

Improvement of virus safety of a S/D-treated factor VIII concentrate by additional dry heat treatment at 100 degrees C.

In order to increase the virus safety of a solvent/detergent-treated Factor VIII concentrate in regard to non-lipid coated viruses and to respond to the continuous discussion about reports on hepatitis A transmission by Factor VIII preparations, we have investigated the effect of a terminal dry heat treatment (30 min 100 degrees C) on HAV and various other viruses. By this treatment Hepatitis A virus was inactivated below detectable level after a few minutes (> 5.3 log10). Other RNA viruses such as the Human Immunodeficiency Virus (> 6.6 log10), bovine viral diarrhoea virus (> 6.6 log10) and vesicular stomatitis virus (> 5.8 log10) were also inactivated below detectable level. Pseudo rabies virus and reovirus Type 3 are inactivated by 5.7 and > 6.0 log10, respectively. SV40 and bovine parvo virus showed significant resistance to dry heat treatment. We conclude that the involvement of two strong virus inactivation steps, acting by different mechanisms, improves the virus safety of Factor VIII concentrates without destroying the Factor VIII activity. Moreover, the terminal 100 degrees C heat treatment for 30 min represents an effective measure to inactivate non-lipid enveloped viruses, in particular hepatitis A, which is resistant to solvent/detergent treatment.

Animals↗
PubMed1996

Arachidonic acid to eicosapentaenoic acid ratio in blood correlates positively with clinical symptoms of depression.

In this study of 20 moderately to severely depressed patients, diagnosed using current research diagnostic criteria and excluding known bipolar affective disorder and reactive depression, we investigated relationships between severity of depression and levels and ratios of n-3 and n-6 long-chain polyunsaturated fatty acids (PUFA) in plasma and erythrocyte phospholipids (PL). Severity of depression was measured using the 21-item Hamilton depression rating scale (HRS) and a second linear rating scale (LRS) of severity of depressive symptoms that omitted anxiety symptoms. There was a significant correlation between the ratio of erythrocyte PL arachidonic acid (AA) to eicosapentaenoic acid (EPA) and severity of depression as rated by the HRS (P < 0.05) and the LRS for depression (P < 0.01). There was also a significant negative correlation between erythrocyte EPA and the LRS (P < 0.05). The AA/EPA ratio in plasma PL and the ratio of erythrocyte long-chain (C20 and C22 carbon) n-6 to long-chain n-3 PUFA were also significantly correlated with the LRS (P < 0.05). These findings do not appear to be simply explained by differences in dietary intake of EPA. We cannot determine whether the high ratios of AA/EPA in both plasma and erythrocyte PL are the result of depression or whether tissue PUFA change predate the depressive symptoms. We suggest, however, that our findings provide a basis for studying the effect of the nutritional supplementation of depressed subjects, aimed at reducing the AA/EPA ratio in tissues and severity of depression.

Adult↗
PubMed1995

Changing incidence and geographical distribution of malignant paediatric germ cell tumours in the West Midlands Health Authority region, 1957-92.

The West Midlands Regional Children's Tumour Research Group holds high-quality data from 1957 on all childhood cancers in the West Midlands Health Authority region. Since it has been reported that malignant germ cell tumours are increasing in incidence in the north-west of England, we undertook to examine rates in this region and to map the distribution of cases in order to assess any geographical changes in incidence rates. We identified a total of 102 malignant germ cell tumours (MGCTs) between 1957 and 1992. The average age-standardised rate was 1.6 per million per year in the period 1957-74 and 3.6 per million per year during 1975-92, a significant increase (P = 0.0004). Particular increases were noted in older children (10-14 years); P = 0.0002) and in yolk sac (endodermal sinus) tumours (P = 0.004). A small excess was also observed in Asian children when compared with other diagnoses. Geographical analysis showed particularly higher rates at health district level in the West Midlands conurbation as compared with the other areas in the period 1975-92. These factors suggest the possibility that industrial/urban or population effects may be implicated in the observed increase in childhood MGCT and we recommend these areas for further studies.

Adolescent↗
PubMed1995

Subtle symptoms associated with self-reported mild head injury.

We conducted a survey on the relationship between mild head injury incidence and a variety of psychological and educational symptoms in a sample of 1,345 high school and 2,321 university students. Once figures were adjusted to represent a 50:50 gender ratio, 30% to 37% of subjects reported having experienced a head injury incident, with 12% to 15% of the total group of subjects reporting such an incident with loss of consciousness. We found significant relationships between the incidence of such mild head injury and gender, sleep difficulties, social difficulties, handedness pattern, and diagnoses of attention deficit, depression, and speech, language, and reading disorders.

Adolescent↗
PubMed1994

If you can replicate the handedness-immune disorder effect, the more power to you.

Bryden, McManus, and Bulman-Fleming's (1994) meta-analysis of studies examining the Geschwind-Behan-Galaburda hypothesis indicates that the original data set supports the hypothesis significantly more than the body of replication attempts. We present data on 2256 subjects that clearly fail to support the hypothesis and describe practical and statistical reasons suggesting why the original data cannot be easily replicated. A power analysis suggests that to find the effect in a general sample, one should plan to have 17,000 to 40,000 subjects.

Child↗
PubMed1994

Glutamate-induced apoptosis results in a loss of striatal neurons in the parkinsonian rat.

The motor symptoms of Parkinson's disease are caused by an increase in activity of striatal neurons which project to the globus pallidus. The discharge activity of these striatal cells is normally regulated by a balance between an inhibitory nigral dopamine input and an excitatory cortical glutamate input. The loss of nigrostriatal dopamine in Parkinson's disease allows the cortical glutamatergic input to dominate (see Fig. 1). Pharmacological or surgical manipulations which redress this imbalance in activity in the striatum, or prevent its propagation throughout the basal ganglia, alleviate the motor symptoms of Parkinsonism. We present evidence to suggest the existence of an endogenous mechanism which compensates for the striatal imbalance during the early stages of Parkinsonism. In the rat rendered parkinsonian by systemic administration of reserpine, selective deletion of striatal neurons was observed. The dying striatal neurons exhibited all of the morphological and biochemical hallmarks of apoptosis. This apoptotic cell death was blocked by either administration of glutamate antagonists or decortication. Our data demonstrate that unchecked endogenous glutamate can induce apoptosis of striatal projection neurons in vivo. This observation may have relevance to the neurophysiological mechanisms which maintain the balance of neural activity within the CNS and to the pathology of neurological diseases.

Animals↗
PubMed1993

A phase I clinical trial of murine monoclonal antibody D612 in patients with metastatic gastrointestinal cancer.

In a phase I study, 21 patients with metastatic adenocarcinoma of the gastrointestinal tract received the murine monoclonal antibody D612. This antibody is directed at a M(r) 48,000 antigen restrictively expressed on tumors of the gastrointestinal tract and to a limited degree on normal gastrointestinal mucosa. Patients received total doses of 10-180 mg/m2 administered as single or multiple doses of 1-100 mg/m2 over an 8-day period. Dose-limiting toxicity was secretory diarrhea. A single dose of 100 mg/m2 exceeded guidelines for maximal tolerated dose. Higher total doses were achieved in subsequent patients by using repeated administration of lower doses. Three of five patients receiving 60 mg/m2 for 3 doses (180 mg/m2 total dose) experienced grade 3 diarrhea and could not complete the prescribed course. The dose of 40 mg/m2 administered on days 1, 4, and 8 (total dose, 120 mg/m2) has been selected as the dose for phase II studies. The pharmacokinetics of D612 is best described by a one-compartment model with a mean t1/2 of 48 +/- 3 h (SEM). Eighteen of 21 patients developed human anti-mouse antibody (HAMA). Patients who developed high levels of HAMA demonstrated a more rapid clearance of the day 8 dose than those who developed low levels of HAMA. In all patients studied, a component of HAMA was directed at the D612 variable region. With one exception, serum from all patients with detectable antibody to the D612 variable region demonstrated anti-paratope reactivity. Thirty-four % of known metastatic sites demonstrated uptake of radiolabeled D612. There were no objective antitumor responses in this phase I trial. The antitumor effect of D612 in vitro has been shown to be potentiated by interleukin 2 and recombinant human macrophage colony-stimulating factor. A phase II study of D612 administered in combination with cytokines that enhance human effector function is presently ongoing.

Adenocarcinoma↗
PubMed1993

Cold tolerance and water content of current-year red spruce foliage over two winter seasons.

Red spruce (Picea rubens Sarg.) in high elevation forests of northeastern North America suffers from frequent and severe winter injury, leading to apical dieback, decreased growth, and high mortality. To examine the role of winter desiccation and freezing injury in winter damage, weekly assessments of cold tolerance and water content were made on current-year foliage collected from native red spruce trees at a high elevation site over two winter seasons. In both years, foliage maintained high water contents and adequate cold tolerance; nonetheless, slight to moderate injury was observed each year on some trees. Despite brief thaw periods each winter, no mid-winter dehardening sufficient to put foliage at risk of freezing injury was evident. These findings suggest that, at least in some years, winter injury to current-year red spruce foliage is produced by a mechanism other than desiccation or absolute low temperatures.

Journal Article↗
PubMed1993

Supplemental oxygen does not reduce myocardial ischemia in premedicated patients with critical coronary artery disease.

This randomized, prospective clinical study investigated the effects of supplemental inspired oxygen on arterial hemoglobin desaturation and myocardial ischemia in premedicated patients who have critical coronary artery stenosis, identified predictors for these adverse events, and examined the temporal relationship between hemoglobin desaturation and myocardial ischemia. Before elective coronary artery bypass surgery, 104 patients were monitored continuously by using a real-time electrocardiogram (V4 and V5 leads) recorder and a digital pulse oximeter. After a 2-h baseline monitoring period (Interval A), patients were given sublingual lorazepam 0.03 mg/kg, and were randomized to receive continuous supplemental inspired oxygen by nasal catheters [4 L/min (Oxygen Group, n = 52)] or to receive no supplemental inspired oxygen (Control Group, n = 52) (Interval B). One hour later, all patients received intramuscular morphine 0.15 mg/kg with perphenazine 0.05 mg/kg (Interval C). Interval C lasted 1 h, and the study was terminated. In the Oxygen Group, the incidence of desaturation was 25% before premedication and 11.5% after premedication (NS). In the Control Group after premedication, the incidence of desaturation increased from 25% to 56.9% (P < 0.001). There was no significant difference in the incidence of myocardial ischemia before or after premedication within or between the two groups. Arterial hemoglobin desaturation was not associated temporally with myocardial ischemia at any time. Predictors of desaturation after premedication included absence of supplemental O2, increased weight, age, and occurrence of desaturation before premedication. There were no identifiable predictors for myocardial ischemia after premedication. During Intervals A and C, episodes of hemoglobin desaturation were associated with small but statistically significant increases in mean heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Phase I trial of the murine monoclonal anti-GD2 antibody 14G2a in metastatic melanoma.

In a phase I trial, 12 patients with GD2 antigen-positive metastatic melanoma received the murine anti-GD2 monoclonal antibody 14G2a. The monoclonal antibody was administered in four doses over an 8-day period with total dose ranging from 10 to 120 mg. All patients receiving greater than 10 mg of 14G2a experienced transient abdominal/pelvic pain during the antibody infusion. Five patients had a delayed extremity pain syndrome following the third and fourth antibody infusion. Four of the five patients developed neurological toxicity, including two patients with significant although reversible motor neuropathy. Two of the patients developed hyponatremia secondary to a syndrome of inappropriate antidiuretic hormone. All 12 patients developed high levels of human anti-14G2a antibody. The plasma half-life of 14G2a was 42 +/- 6 (SD) h. One patient each had a partial response, mixed response, and stable disease, respectively. The very modest antitumor activity accompanied by dose-limiting neurological toxicity at total doses greater than 80 mg may restrict the clinical utility of murine 14G2a.

Antibodies, Monoclonal↗