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Biomedical subjects

D Shanks

Publications and source records attributed to D Shanks.

At least 19 recordsLinked to original sources
PubMed2002

In vitro RBC exposure to Plasmodium falciparum has no effect on RBC antigen expression.

Severe malarial anaemia is a leading cause of death in African children younger than 3 years of age who are infected with Plasmodium falciparum. The pathogenesis of this anaemia is not understood. The purpose of this study was to determine if P. falciparum induces changes in RBC membranes that contribute to the immune destruction of RBCs. RBCs were collected from healthy subjects and tested using standard haemagglutination assays for 45 antigens representing 21 blood group systems/collections before and after exposure to P. falciparum, strain FVO. Lectins were used to determine whether crypt or neoantigens were expressed on the RBC membrane. Polybrene was used to detect changes in sialic acid. RBCs were cultured in vitro with and without the parasite, and blinded serologic studies were completed. CD35 (complement receptor 1), CD55 (decay-accelerating factor), CD59 (membrane inhibitor of reactive lysis) and CD47 (integrin-associated protein) flow cytometric assays were compared for infected and uninfected RBCs. The percentage of parasitaemia was determined using Giemsa-stained thin blood films. Two (Ch, Lub) of the 45 antigens had differing strengths of agglutination between infected and uninfected RBCs, but these differences were resolved with a second source of antisera. Forty-three antigens showed no significant differences in the strength of agglutination between the infected and uninfected RBCs. Lectin and polybrene testing showed no differences. CD35, CD55, CD59 and CD47 levels showed no significant differences. P. falciparum does not appear to alter the expression of classified immunogenic antigens on the RBC membrane in this in vitro system. The pathogenesis of the haemolytic episode that occurs in these children remains unclear.

Animals↗
PubMed2001

Bones, groans and blasts.

A 14-year-old girl presented with the acute onset of gastrointestinal symptoms due to hypercalcaemia. Chest X-ray revealed osteolytic lesions in the ribs which in conjunction with a normal parathyroid hormone level raised the possibility of malignancy. Despite the absence of blast cells in her blood film, the bone marrow biopsy was diagnostic of acute lymphoblastic leukaemia. She responded well to treatment with pamidronate and chemotherapy.

Adolescent↗
PubMed1997

Psychometric assessment of motives for using cocaine in men with substance use disorders.

A 15-item self-report questionnaire from a previous study of social, coping, and enhancement motives for drinking was reworded to assess motives for using cocaine. Data from 121 cocaine users indicated satisfactory reliabilities for the 3 new 5-item scales, and the fit of a 3-factor structure in confirmatory factor analysis was comparable to that of the earlier study of drinking motives. Removal of 4 items substantially improved the fit to the 3-factor model without reducing reliabilities. Some evidence of validity was inferred from a correlation between reported use of cocaine for coping and a measure of general maladjustment.

Adaptation, Psychological↗
PubMed1994

Influence of azathioprine on the ferrokinetics of patients with renal failure before and after treatment with erythropoietin.

In 16 patients (9 on azathioprine, 7 not) the ineffective iron turnover (IIT) was much higher in the azathioprine group (62.7 +/- 6.7 vs. 23.5 +/- 3.5 mumol/l blood/day, p < 0.0001, 2-tailed t test), though the red cell iron turnover (RCIT) was similar (42.8 +/- 2.9 vs. 41 +/- 4.8). Erythropoietin improved the anaemia in all patients and raised the RCIT (4 still on azathioprine to 72.2 +/- 9.8, p < 0.003; 7 non-azathioprine patients to 62.7 +/- 5.3, p < 0.01); the IIT remained higher in the azathioprine-treated (85.5 +/- 19.3 vs. 37.1 +/- 5.4; p < 0.013). In 2 patients who discontinued azathioprine, the IIT declined markedly to normal. In summary, azathioprine exacerbates the anaemia of renal failure by augmenting ineffective erythropoiesis, while erythropoietin benefits those on azathioprine as much as other renal patients by stimulating both effective and ineffective erythropoiesis.

Anemia↗
PubMed1993

Kawasaki disease--the Northern Ireland experience.

In the period 1985-1991 inclusive, forty five cases of Kawasaki Disease were identified in Northern Ireland. The number of cases increased each year until 1988 when the incidence was 19 per million population under 16 years, the highest reported for any region in the United Kingdom (data from British Paediatric Surveillance Unit). A high incidence of cardiac involvement was found, with 18(40%) having proximal coronary artery dilatation or aneurysm. and 8(17.7%) with pericardial effusion detected by 2D Echocardiography during or shortly after the acute illness. One year after disease onset, persistent coronary artery changes were detectable by 2D Echocardiography in 53% of those initially affected. There have been no deaths and no patient has so far developed myocardial infarction. One patient has required coronary artery bypass grafting. A protocol for the acute management and long term follow-up of Kawasaki Disease is suggested.

Child↗
PubMed1993

Effects of azathioprine on response of renal anaemia to subcutaneous recombinant human erythropoietin.

AIMS: To determine the effect of concomitant azathioprine treatment on the response of patients with renal failure to treatment with subcutaneous recombinant human erythropoietin (r-HuEPO). METHODS: Two groups of patients with renal failure not receiving haemodialysis were studied. One comprised seven patients receiving erythropoietin alone, the second consisted of nine patients who were also treated with azathioprine. The haematological changes were monitored, and the functional erythropoietic response was studied by two different ferrokinetic models. One analysed the initial, the other the extended plasma iron clearance. Studies were performed before r-HuEPO treatment on all 16 patients, and repeated on 11 of these when the target haemoglobin (10-11 g/dl) was achieved and stabilised. Total erythropoiesis was determined using both techniques. Analysis of the extended plasma iron clearance also permitted calculation of both effective and ineffective erythroid activity. RESULTS: The haematological response to r-HuEPO was the same for both patient groups. Measurement of total erythropoiesis by both ferrokinetic methods showed good correlation. For those receiving long term azathioprine, the percentage ineffective erythropoiesis was high compared with that of the other patients, and remained so for as long as they continued with azathioprine. For those uncomplicated by azathioprine treatment, r-HuEPO increased levels of both effective and ineffective erythropoiesis by the same degree. A substantial reduction in ineffective erythropoiesis was shown only by those patients who either discontinued or reduced their azathioprine once they started r-HuEPO treatment. CONCLUSIONS: Azathioprine increases ineffective erythropoiesis. In this study, the r-HuEPO dose was sufficient to overcome this effect and promoted effective erythropoiesis so that the anaemia lessened. Measurement of total erythropoiesis provided limited information on the functional changes involved, differentiation of effective from ineffective erythropoiesis being necessary to define the changes after azathioprine reduction or withdrawal.

Anemia↗
PubMed1993

Monitoring of iron requirements in renal patients on erythropoietin.

We studied 38 patients (9 haemodialysis, 18 peritoneal dialysis, 11 advanced renal failure) over the first 12 weeks of erythropoietin therapy. In 14 iron-overloaded patients (ferritin > 500 micrograms/l the haemoglobin (+/- SEM) increased from 6.74 +/- 0.27 to 9.85 +/- 0.36 g/dl (P < 0.0001) entirely by mobilizing iron reserves (reduced from 1,220 +/- 73 to 739 +/- 111 mg, P < 0.0001). In the 24 non-overloaded patients (ferritin < 500 micrograms/l) the haemoglobin rose similarly from 7.04 +/- 0.18 to 10.70 +/- 0.36 g/dl (P < 0.0001), partly from iron reserves (depleted from 200 +/- 74 to -44 +/- 77 mg, P = 0.016) and partly from oral iron supplements (305 +/- 110 mg). In the overloaded patients the ferritin declined from 1057 micrograms/l (geometric mean, range 504-3699) to 317 micrograms/l (42-1505, P < 0.0001). In the non-overloaded patients it declined from 82 micrograms/l (8-461) to 45 micrograms/l (5-379, P = 0.016). The transferrin saturation (TS) in the overloaded patients appeared to decline from 38.3 +/- 7.2% to 24.0 +/- 3.7% but this was not statistically significant. In the non-overloaded the TS was unchanged (23.3 +/- 2.4 before and 28.1 +/- 3.6% after treatment). Considering all 38 patients together, the haemoglobin correlated negatively with the ferritin (r = 0.3731, P < 0.001) but not with the TS. The TS correlated with the serum ferritin initially (r = 0.75, P < 0.001) but not after the first 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Influence of blood volume on the blood pressure of predialysis and peritoneal dialysis patients treated with erythropoietin.

Twenty-seven patients with renal failure (16 on CAPD and 11 predialysis) were treated with erythropoietin. At 12 weeks, the mean haemoglobin concentration (+/- SEM) in the CAPD patients had increased from 7.07 +/- 0.20 to 10.88 +/- 0.45 g/dl (two-tailed paired t test, P < 0.0001) and in the predialysis patients from 6.90 +/- 0.35 to 10.05 +/- 0.47 g/dl (P < 0.0001). Predialysis patients were taking more antihypertensive medication at baseline. No increase was required in either group after erythropoietin; there was no change in blood pressure in the CAPD patients, though in the predialysis patients the systolic blood pressure rose slightly from 132 to 146 mmHg (P = 0.029) and the mean blood pressure from 95 to 103 mmHg (P = 0.028). In 12 patients (6 on CAPD and 6 predialysis) the red cell volume, plasma volume, and total blood volume were measured before and after treatment. In the CAPD patients there was a marked expansion of the red cell volume from 912 +/- 127 to 1471 +/- 222 ml (P = 0.004) and a concomitant contraction of the plasma volume from 3932 +/- 250 to 3178 +/- 326 ml (P = 0.005), leaving the blood volume unchanged from 4843 +/- 352 to 4649 +/- 503 ml. Predialysis patients had a similar expansion of the red cell volume from 733 +/- 59 to 1304 +/- 161 ml (P = 0.017) but no contraction of the plasma volume (from 3417 +/- 354 to 3314 +/- 260 ml), so that the blood volume tended to expand from 4149 +/- 347 to 4618 +/- 414 ml (P = 0.053).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1991

Comparative ferrokinetic study with initial and extended iron clearance models.

Erythrokinetic studies were performed on 10 patients with chronic myelofibrosis and 11 patients with myelodysplasia (MDS). Values for plasma iron turnover, marrow iron turnover, and erythron transferrin uptake were derived using two ferrokinetic models. One entailed analysis of the extended plasma iron clearance over a number of days, the other comprised analysis of the initial plasma iron clearance during the first few hours of the study. A close correlation was found between the variables quantifying total erythropoiesis (marrow iron turnover and erythron transferrin uptake) in the two methodologies. Functional classifications produced by both models and based on the values for plasma iron turnover, marrow iron turnover, and erythron transferrin uptake were compared. Both models identified functional heterogeneity in the group with myelofibrosis and functional homogeneity within the MDS group. Each method produced comparable data on erythropoiesis. The main reason for analysing the extended plasma iron clearance is to differentiate levels of effective and ineffective erythropoiesis. The short analysis presents the practical advantages associated with a one-day study. This could be further enhanced if the level of effective erythropoiesis could be clearly defined.

Bone Marrow↗
PubMed1991

Malaria as a military factor in Southeast Asia.

Malaria remains a major cause of military casualties in Southeast Asia. The numerous conflicts in the region have been greatly affected by malaria. Besides guerrilla warfare, refugees and other civilian movements across international borders contribute heavily to the continuing problem of multiple drug-resistant malaria. Drug resistance is an increasing problem with few available prophylactic options. The malaria threat to any potential deployment of United States military forces remains unsolved.

Asia, Southeastern↗
PubMed1989

Malaria prophylaxis with doxycycline in soldiers deployed to the Thai-Kampuchean border.

A battalion of Royal Thai Marine militia was assigned to take either 50 mg or 100 mg of doxycycline daily or pyrimethamine/dapsone weekly for malaria prophylaxis on the Thai-Kampuchean border for a 17 week period. Attack rates for the groups expressed as cases/100 men were 34 for 50 mg doxycycline, 18 for 100 mg doxycycline, and 52 for pyrimethamine/dapsone. The relative efficacy of the two doxycycline regimens compared to Maloprim were 1.6 and 1.4. Compliance with the daily drug nearly equalled that of the weekly regimen. This suggests that 100 mg of doxycycline daily can be effectively used for malaria prophylaxis by soldiers under operational conditions on the Thai-Kampuchean border.

Antimalarials↗