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Biomedical subjects

E A Nelson

Publications and source records attributed to E A Nelson.

133 records · Page 8Linked to original sources

Thalassaemia trait, red blood cell age and oxidant stress: effects on Plasmodium falciparum growth and sensitivity to artemisinin.

Knowledge of innate mechanisms of protection against malaria could be used to bolster the existing limited treatments. Oxidant stress may play a role in the protective mechanism and the effect of red blood cell (RBC) age has recently been recognized. This study investigated the role of oxidant stress in the protection against malaria in thalassaemic trait RBC (alpha and beta) using an experimental approach which controlled for cell age. 'Young', 'intermediate' and 'old' RBC obtained by Percoll fractionation and whole blood were used to set up malaria cultures. Antioxidants (vitamin E and dithiothreitol) and pro-oxidants (riboflavin, menadione and artemisinin) were added to modulate oxidant stress effect. Antioxidants improved parasite growth. The degree of improvement was significantly greater with increasing RBC age (P < 0.0001), and relatively greater in thalassaemic RBC (P < 0.0001). Pro-oxidants had a parasiticidal effect. With the exception of the 'old' RBC fraction, the median inhibitory concentration (IC50) for riboflavin and menadione was significantly higher in normal RBC. In contrast, the IC50 for artemisinin was significantly higher in 'old' thalassaemic RBC but was similar in the 'young' and 'intermediate' fractions and whole blood. These findings suggest that oxidant stress plays a role in mediating the protection against malaria in thalassaemic RBC. Vitamin E and other antioxidant supplementation could feasibly exacerbate clinical malaria. Conversely, pro-oxidant agents could act as useful adjuvants to therapy. It is important to confirm the reduced sensitivity to artemisinin in 'old' thalassaemic trait RBC, as such an effect may promote selective pressure for the emergence of resistant parasite strains with widespread use of artemisinin.

Age Factors↗

Invasion and growth of Plasmodium falciparum is inhibited in fractionated thalassaemic erythrocytes.

Epidemiological and clinical studies have indicated that the thalassaemias may confer protection against malaria. The study reported here investigated this protective effect in vitro, using a new approach which controls for the potential effect of red cell size and age on the virulence of the parasite. A Percoll density gradient method was used to separate alpha- and beta-thalassaemic trait, haemoglobin H and normal red blood cells (RBC) into fractions of different density. Correlations between RBC density, age and size in fractions of all genotypes were established using red cell creatine as an index of cell age. The development of Plasmodium falciparum over 3 erythrocytic cycles (144 h) in whole blood as well as fractionated samples was monitored by slide microscopy and flow cytometry. A significantly reduced rate of parasite invasion and growth was demonstrated in RBC from all thalassaemic genotypes tested. Poor reinvasion rates were noted in the second and third cycles. Increased duration of culture and red cell age also had a greater negative impact on parasite growth in thalassaemic RBC. This poor growth rate was also associated with the arrest of parasite growth at the schizont stage (schizont maturation arrest) and the accumulation of abnormal, trophozoite/schizont stage parasites in the older thalassaemic RBC fractions. These findings suggest a defect in the number and viability of merozoites generated by parasites growing in thalassaemic RBC. Age related factors such as oxidant stress may play a key role in mediating this kind of protective mechanism and deserve further investigation.

Animals↗

Epidemiology of pediatric EMS practice: a multistate analysis.

OBJECTIVE: To describe the epidemiology of pediatric emergency medical services (EMS) practice in a large patient population from several geographic areas. DESIGN: Retrospective computer analysis of EMS databases from four states using a common data set and analysis system. SETTING: Pennsylvania, Tennessee, Mississippi, and Nevada (except Clark County), 1990 through 1992. METHODS: All patient-care reports of patients 14 years old and younger were extracted from the EMS databases and analyzed for the following factors: age, gender, date, elapsed prehospital times, incident type, mechanism of injury, call disposition, illness or injuries encountered, severity of illness/injury (by abnormal vital signs), and basic life support (BLS) and advanced life support (ALS) treatment delivered. RESULTS: A total of 1,512,907 patient care reports were reviewed. Those of 61,132 children were extracted for analysis. These children comprised about 4% of prehospital responses. Male subjects predominated (56%), and children aged 7 through 14 years represented 46% of cases. Most calls occurred in the evening and daylight hours. Children were transported by ambulance in 89% of cases, and care was refused in 7.7%. Mean response time was 9 +/- 16 minutes, mean scene time 12 +/- 14 minutes, and mean transport time 14 +/- 20 minutes. Traumatic incidents predominated at 42%, with motor vehicle accidents and falls the most common mechanisms. Blunt injuries accounted for 94% of trauma, whereas respiratory problems, seizures, and poisoning/overdose were the most common medical problems. Vital signs were obtained in 56% of cases. Abnormal vital signs were noted in 21% of these, and the presumptive causes were similar in distribution to those of the general population, with the addition of cardiac arrest. The most commonly used treatments were spinal immobilization, oxygen administration, intravenous access and several ALS medications. An ALS capability was available in more than half the runs, but ALS treatment was delivered in only 14% of those cases. Outcome data were not available. CONCLUSION: This multistate analysis of pediatric EMS epidemiology confirms findings reported in smaller regional studies, with several exceptions. Excessive scene times were not noted. Few children had serious disorders as evidenced by abnormal vital signs. An ALS treatment, when available, was used infrequently. These findings have implications for EMS planners and educators.

Adolescent↗

Use of compression hosiery in venous leg ulceration.

Venous leg ulceration is a common problem in older people that adversely affects their quality of life. It is also a major cause of morbidity for many patients in hospital and community settings. Patients experience considerable pain and distress as a result of this condition and annual costs to the NHS are high. However, good nursing management and the correct use of compression therapy can lead to faster healing rates (Effective Health Care 1997), and reduced nursing time. This article discusses the use of compression hosiery in the prevention and treatment of venous leg ulcers.

Anthropometry↗