Biomedical subjects

R P Richardson

Publications and source records attributed to R P Richardson.

5 recordsLinked to original sources

PubMed1997

DNA index and % S phase fraction in posterior uveal melanoma: a 5 year prospective study of fresh tissue using flow cytometry.

In many different solid tumours the DNA content of cells has been reported to be associated with malignancy. With one exception, studies using flow cytometry to estimate cellular DNA in uveal melanoma have used archival material. We report the findings of a prospective study using fresh uveal melanoma where the DNA index (DI) and percentage of cells in S phase (%SPF) have been determined by flow cytometry in 51 patients with a minimum follow-up of 5 years. Forty-one (80%) of the tumours were large, 9 (18%) were medium and only 1 was small. Eight (16%) were epithelioid tumours, 41 (80%) were mixed cell and only 2 were spindle B cell tumours. Twenty-seven tumours were diploid, of which 10 (37%) developed metastases. Of the 24 aneuploid tumours, metastases developed in 6 (25%). The median %SPF was significantly reduced in patients with diploid tumours compared with aneuploid tumours (p < 0.0001), but there were no significant differences in %SPF between tumours associated with or without metastatic disease. The DI and %SPF were not significantly associated with the operation performed, cell morphology, tumour size or location. Neither %SPF nor aneuploidy was associated with a poor prognosis. Our results suggest that the estimation of DI or %SPF by flow cytometry is of little value in predicting survival from uveal melanomas after a minimum follow-up of 5 years.

Adult↗

PubMed1990

Pathophysiologic glucocorticoid elevations promote bacterial translocation after thermal injury.

Thermal injury results in transient elevations of plasma glucocorticoids and promotes translocation of bacteria from the gut to the mesenteric lymph nodes (MLN) in rats. Translocated organisms are quickly cleared following uncomplicated thermal injury. However, subsequent burn wound infection, in temporal association with sustained pathophysiologic elevations of plasma corticosterone, results in the continued presence of enteric bacteria in the MLN. To study the role of sustained pathophysiologic steroid elevations in the mediation of this prolonged bacterial translocation, Wistar rats were randomly placed in groups receiving one of the following: (i) a 30% total body surface area scald injury with placement of a subcutaneous corticosterone pellet, (ii) a 30% total body surface area scald and a sham pellet implantation, (iii) a sham burn and a corticosterone pellet implantation, or (iv) a sham burn and a sham pellet implantation. The animals were sacrificed on days 1 and 4 after injury, and cultures of the MLN, as well as the liver and spleen, were taken. Implantation of corticosterone pellets resulted in sustained elevations of plasma corticosterone compared with controls not receiving corticosterone pellets, similar to results seen in association with injury and infection. These pathophysiologic elevations were associated with the prolonged presence of organisms in the MLN (90% of burned rats with implanted corticosterone pellets versus 25% of rats with uncomplicated burns on postburn day 4; P less than 0.01), but only in the presence of burn injury. Pathophysiologic glucocorticoid elevations did not lead to progression of translocation to the viscera or blood. Thus, the pathophysiologic glucocorticoid response contributes to the translocation of enteric bacteria and their prolonged presence in the MLN after systemic injury.

Animals↗

PubMed1989

Hepatocellular membrane function during chronic burn injury.

Hepatocellular membrane dysfunction, as indicated by depolarization of the membrane potential, occurs after acute injury and early bacteremia. To determine whether hepatocellular membrane dysfunction occurs in the setting of ongoing thermal injury and infection, Wistar rats were divided into four groups: (1) sham-burned, freely fed controls (FF); (2) rats sustaining approximately 30% total body surface area dorsal full-thickness scald burn (Burn); (3) rats sustaining burns as in group 2 followed by immediate inoculation of 1 x 10(8) CFU Pseudomonas aeruginosa (Burn/Inf); and (4) sham-burned rats pair-fed to the food intake of the Burn/Inf group (PF). On the third and seventh days postburn, body and liver weights were determined. In vivo hepatocellular transmembrane potentials were measured and hepatic ATP, RNA, DNA, and protein contents were assayed. By Day 7, despite greater weight loss in the Burn/Inf group than due to starvation alone (P less than 0.01 Burn/Inf vs FF and PF), hepatic mass was conserved. This was associated with hyperpolarization of the hepatic transmembrane potential (-46.6 +/- 1.5 vs -32.1 +/- 0.6 mV, Burn/Inf vs FF, P less than 0.01) and increases in RNA (141 +/- 9 vs 91 +/- 4 mg/liver, Burn/Inf vs FF, P less than 0.01) and DNA (37 +/- 5 vs 22 +/- 2 mg/liver, Burn/Inf vs FF, P less than 0.05) contents, with no change in ATP or hepatic protein contents. There was a significant hypercorticosteronemia observed in the Burn/Inf group (43 +/- 9 vs 2.8 +/- 0.7 micrograms/dl, Burn/Inf vs FF, P less than 0.01). This hepatic membrane hyperpolarization and augmented RNA content were not secondary to burn or starvation alone as the response in these groups was significantly less than that of the Burn/Inf group. It is suggested that this hepatic membrane hyperpolarization is one mechanism by which hepatic function is maintained during ongoing burn infection in the rat.

Adenosine Triphosphate↗

PubMed1989

Peripheral blood leukocyte kinetics following in vivo lipopolysaccharide (LPS) administration to normal human subjects. Influence of elicited hormones and cytokines.

Lipopolysaccharide (LPS, endotoxin) administration to human subjects elicits significant elevations in plasma cachectin/TNF, epinephrine, and cortisol. This study examined the temporal relationship between changes in blood leukocyte subsets and plasma mediators following endotoxin administration to normal human subjects. A five-minute intravenous infusion of purified LPS (20 units/kg Escherichia coli) was administered to 12 healthy volunteers. Blood samples were obtained at varying intervals after infusion and analyzed for differential cell counts and lymphocyte subsets (CD2, CD3, CD4, CD8, CD20, and HLA-DR) by flow microfluorimetry, and also assayed for plasma cachectin/TNF, epinephrine, and cortisol. Plasma cachectin/TNF was significantly elevated at 75 and 90 minutes after infusion with a peak concentration of 261 +/- 115 pg/ml noted 75 minutes after infusion. A significant plasma epinephrine elevation of 181 +/- 75 pg/ml was demonstrated one hour after infusion, while significant elevations in plasma cortisol were noted from one to five hours after infusion with a peak level of 34 +/- 3 micrograms/dl three hours after infusion. A profound monocytopenia (p less than 0.01) was noted one hour after infusion. Temporally associated with the rise in plasma cortisol was a reversal of the early granulocytopenia to a significant granulocytosis (p less than 0.01 versus preinfusion mean), whereas a marked lymphocytopenia (p less than 0.01) was observed from one to six hours after infusion. During the period of hypercortisolemia, CD2, CD3, and CD4 lymphocyte percentages were decreased (p less than 0.01) while CD20 and HLA-DR lymphocyte percentages were increased (p less than 0.01). There was a small percentage decrease in CD8 lymphocytes from one to 24 hours after infusion (p less than 0.01), although relative to the one-hour nadir, there was a significant rise in the percentage during the time of elevated plasma cortisol concentrations. A six-hour infusion of epinephrine (30 ng/kg/min) administered to six healthy volunteers resulted in a monocytosis (p less than 0.05) and granulocytosis (p less than 0.01) without a change in lymphocyte number or lymphocyte subset percentage. Previous reports have shown that in vivo corticosteroid infusion causes a prominent granulocytosis, monocytopenia, and lymphocytopenia with a decrease in the percentages of CD3 and CD4 lymphocytes. The peripheral blood leukocyte dynamics documented in the current study are similar to patterns observed following in vivo corticosteroid administration. This study suggests that the acute adrenocortical response to endotoxemia primarily mediates the subsequent changes in leukocyte subsets.

Adult↗

PubMedDate not supplied

Chronic pathophysiologic elevation of corticosterone after thermal injury or thermal injury and burn wound infection adversely affects body mass, lymphocyte numbers, and outcome.

The purpose of the present studies was to investigate the effect of glucocorticoids on catabolism and lymphocyte numbers in a rat model of thermal injury or thermal injury plus burn wound infection. Thermal injury alone caused only an acute increase in plasma corticosterone concentrations. Furthermore, body weight declined moderately (5%), and lymphocyte numbers in lymph nodes draining the burn wound and blood increased markedly, whereas splenic lymphocyte numbers declined by about 60%. By contrast uninjured rats subjected to chronic elevation of corticosterone by corticosterone pellet implantation showed large decreases in body weight and lymphocyte numbers in all tissues examined. The combination of injury and chronic corticosterone elevation resulted in body weight and lymphocyte changes intermediate between injury alone and corticosterone treatment alone. Chronic elevation of corticosterone for 4 days before burn wound infection significantly decreased survival time and survival. Burn wound infection immediately after injury caused chronic elevation of endogenous plasma corticosterone and body weight and numeric lymphocyte changes that were remarkably similar to those of uninjured rats treated with corticosterone. Finally, the glucocorticoid receptor antagonist RU 486 significantly increased survival time in thermally injured, burn wound-infected rats. These results lend support to a hypothesis that chronic elevation of plasma cortisol concentrations as observed in patients with burns may be deleterious.

Analysis of Variance↗