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Biomedical subjects

R H Harris

Publications and source records attributed to R H Harris.

At least 37 records · Page 2Linked to original sources
PubMed1981

Thromboxane, prostacyclin, and hemodynamic events in primate endotoxin shock.

Prostaglandins participate in the pathophysiology of septic shock; however, their exact role is unclear. In this study we investigated the possibility that thromboxane and prostacyclin, the most recently discovered prostaglandins, may be related to the pulmonary arterial hypertension (thromboxane) and systemic arterial hypotension (prostacyclin) during endotoxin shock in the baboon. There are no previously reported studies in the subhuman primate. In this study ten male baboons received an LD70 dose of E. coli endotoxin. Cardiac output, mean systemic arterial pressure, pulmonary arterial pressure, blood gases, WBC and platelet counts, and prostaglandins were determined at 0, 15, 60, 120, 180, and 240 minutes. Thromboxane and prostacyclin levels were significantly (P less than 0.05) increased after the endotoxin injection. Systemic arterial PGI values increased within 15 minutes, peaked at two hours, and was directly related to the fall in systemic arterial pressure (r = 0.93). In contrast, thromboxane values peaked at 15 minutes and directly related (r = 0.90) to the rise in pulmonary artery pressure. Thromboxane and prostacyclin are significantly increased in subhuman primate endotoxin shock. The temporal relationship of thromboxane and pulmonary arterial pressure suggests that thromboxane may mediate the effects of endotoxin on the pulmonary vasculature.

Animals↗
PubMed1980

Obstructive nephropathy in the rat: possible roles for the renin-angiotensin system, prostaglandins, and thromboxanes in postobstructive renal function.

Relief of unilateral ureteral obstruction (UUO) of 24 h duration in rats is followed by severe renal vasoconstriction in the postobstructive kidney (POK). The present study examined possible roles of renal prostaglandins (PG) and thromboxanes (TX), as well as the renin-angiotensin system, in this vasoconstriction. Administration of the cyclooxygenase inhibitor indomethacin, which blocks both PG and TX production, failed to improve POK hemodynamics in UUO rats. To explore the possible role of the TX compounds, which include the potent vasoconstrictor thromboxane A2 (TXA2), UUO rats were infused with imidazole, an agent that blocks synthesis of TX, but not of PG. Imidiazole led to two- to threefold increases in the clearance of both inulin and rho-aminohippuric acid by the POK. This effect of imidazole was abolished by indomethacin, suggesting that the amelioration of POK vasoconstriction by imidazole was a result of inhibition of vasoconstrictor TX synthesis (e.g. TXA2), with PG vasodilators (e.g. PGE2 or PG12) still active. Urea, infused in a solution whose osmolality and volume were identical to the imidazole infusion, failed to improve hemodynamics in the POK, making it unlikely that nonspecific effects of volume expansion or osmotic diuresis mediated the beneficial effect of imidazole. Further studies examined the possible role of the renin-angiotensin systems in the vasoconstriction of the POK. UUO rats infused with the angiotensin II antagonist, Saralasin, exhibited no significant improvement in POK function, a finding that might be at least partly attributable to agonist/vasoconstrictor properties of Saralasin. In other experiments, treatment of UUO rats with the angiotensin-converting enzyme blocker SQ 14225 (Captopril), in order to inhibit angiotensin II formation, led to at least twofold increases in the clearance of both inulin and rho-aminohippuric acid in the POK. It is unlikely that Captopril exerted this beneficial effect by potentiating the vasodilator kinins, because the effect was not diminished by administration of either carboxypeptidase B (which destroys the kinins) or Trasylol (which blocks kinin synthesis). Thus, these results suggest that both angiotensin II, as well as metabolites of the PG-TX system, may be important determinants of postobstructive renal hemodynamics in the rat.

Angiotensin II↗
PubMed1979

Cellular mechanisms of prostaglandin action.

The human platelet and erythrocyte differ quite dramatically in relation to the arachidonic acid cascade. The platelet synthesizes its own characteristic products, while the erythrocyte lacks cyclo-oxygenase activity but possesses other metabolic enzymes. In these and other cell types the metabolites are potentially determined by the cascade enzymes, the availability of cofactors, the presence of specific activators and inhibitors, and the selective binding or transport of intermediates. Endogenously synthesized metabolites may have intracellular actions or may be released and exert their effects extracellularly. Study of the cellular mechanisms mediating these effects, like study of the fast-acting hormones, has focused primarily on the cyclic nucleotides and calcium. Considering the diverse activities of several metabolites in the platelet however, these mechanisms seem to need reevaluation or refining. The released cascade metabolites may also act as intercellular signals over a short range. The range depends on their chemical stability in the absence of protective carriers and their selective uptake and metabolism by surrounding cells. Additionally, the effects will reflect the selective interaction of responsive cells with the spectrum of metabolites released. Answering these questions of complex intercellular interactions requires the identification and classification of characteristic responses and the metabolic profile of individual cell types in each tissue. Consequently, this type of analysis may best be done with isolated cells, such as the platelet and erythrocyte.

Arachidonic Acids↗
PubMed1979

Slowly dialyzable stimulators of renal protein synthesis in urine.

Previously, we demonstrated that continuous intravenous reinfusion of half the urine output (1/2UR) in rats for 1 wk led to increased renal mass. This suggested that reduced renal excretory function, or the retention of urinary factors, was capable of stimulating renal growth. The present study was designed to examine renal protein synthesis during the early phase of this growth and to better define the nature of the stimuli. Compared with matched sham-manipulated control rats, rats subjected to 24 h of 1/2UR displayed significant increases in both the incorporation of tritiated leucine into protein and in the cellular uptake of leucine by renal cortical tissue in vitro. In addition, total protein content of the kidneys, but not of the liver, was significantly increased after 24 h of 1/2UR. Dialysis of urine prior to its reinfusion did not diminish, but rather augmented, the incorporation of leucine into renal protein. These results suggest that renal protein synthesis can be stimulated by the retention of factors in the urine that are poorly dialyzable.

Animals↗
PubMed1979

Ureteral catheter system for renal function studies in conscious rabbits.

To overcome the problem of obstruction of ureteral catheters with blood clots, a ureteral catheter was constructed which had a double lumen. Irrigation of blood from the catheter was accomplished by perfusion of heparinized saline through a small inner catheter. In renal function studies performed in 12 rabbits using this system, no instances of catheter obstruction occurred.

Animals↗
PubMed1977

Urine-reinfusion natriuresis: evidence for potent natriuretic factors in rat urine.

In awake rats the entire urine output was continuously reinfused i.v. Urine-reinfusion (UR) consistently led to the appearance, within one to two hours, of massive, sustained natriuresis and diuresis, suggesting the existence of potent natriuretic factors in the urine. At the time of maximal natriuresis, mean sodium excretion rate and urine flow rate were 25 and 15 times their respective values in control rats. Ths "urine-reinfusion natriuresis" could be demonstrated despite treatment with desoxycorticosterone acetate, blockage of prostaglandin synthesis by indomethacin or meclofenamate, reduction of plasma urea by pretreatment with a protein-free diet, or heating the urine to 100 degrees C. The natriuresis was not prevented by the absence of vasopressin (in Brattleboro rats) and was augmented by vasopressin infusion. In the Brattleboro rats, a marked increase in (CH2O + CNa)/GFR with only a slight rise in CH2O/GFR during UR suggests inhibition of both proximal and distal tubular reabsorption. Renal blood flow and plasma flow increased markedly during UR with a lesser rise in GFR, consistent with post-glomerular vasodilatation. Thus, the phenomenon of urine-reinfusion natriuresis suggests the presence in rat urine of potent, heat stable natriuretic factors, whose action is largely independent of changes in mineralocorticoids, prostaglandins, urea, or vasopressin. Renal vasodilatation with decreased sodium reabsorption at both proximal and distal nephron sites, appears to play an important role in the natriuresis.

Absorption↗
PubMed1976

Drinking water and cancer mortality in Louisiana.

Multivariant regression analysis indicates a statistically significant relation between cancer mortality rates in Louisiana and drinking water obtained from the Missippi River. This is true for total cancer, cancer of the urinary organs, and cancer of the gastrointestinal tract.

Breast Neoplasms↗
PubMed1976

Bilateral pulmonary hilar lymphadenopathy. An unusual manifestation of metastatic renal cell carcinoma.

Four patients with bilateral pulmonary hilar adenopathy secondary to lymphangitic spread from renal cell carcinoma were examined. Two additional cases had adenopathy secondary to nasopharyngeal carcinoma. Patients may initially present with bilateral pulmonary lymphadenopathy or as late as 3 1/2 years after the discovery of the primary renal tumor. The mechanism of lymphangitic spread probably is related to reflux of tumor emboli from the thoracic duct into the bronchomediastinal trunks because of incompetent lymphatic valves. In one case gallium imaging demonstrated bilateral hilar isotopic uptake as well as periaortic uptake.

Adenocarcinoma↗