PubMed Health⌕ Search

Biomedical subjects

J Haynes

Publications and source records attributed to J Haynes.

At least 55 records · Page 3Linked to original sources

U74500A inhibition of oxidant-mediated lung injury.

Toxic oxygen species are thought to play a primary role in the pathophysiological mechanisms responsible for a diverse group of lung diseases. In this study, isolated perfused rat lungs were subjected to oxidant injury induced by ischemia-reperfusion (IR) and t-butyl hydroperoxide (t-buOOH) challenge. Both forms of injury caused large increases in capillary permeability as assessed by the capillary filtration coefficient (Kfc). IR and t-buOOH challenge caused increases in the Kfc of 0.95 +/- 0.22 and 0.30 +/- 0.06 ml.min-1.cmH2O-1.100 g lung tissue-1, respectively. U74500A, a potent inhibitor of iron-mediated lipid peroxidation, significantly attenuated the endothelial damage seen in both forms of injury. In lungs pretreated with U74500A, the Kfc increased 0.01 +/- 0.02 and 0.11 +/- 0.03 ml.min-1.cmH2O-1.100 g lung tissue-1 following IR and t-buOOH challenge, respectively. In lungs pretreated with the iron binding protein transferrin the Kfc increased 0.31 +/- 0.11 and 0.19 +/- 0.03 ml.min-1.cmH2O-1.100 g lung tissue-1 following IR and t-buOOH challenge, respectively. In these studies, transferrin significantly attenuated permeability in the IR group only. However, the attenuation of injury in IR due to U74500A was significantly greater (P less than 0.05) than the attenuation provided by transferrin. Both forms of injury also caused small but statistically significant increases in pulmonary artery pressure. These results suggest that the increase in capillary permeability seen after IR and t-buOOH is in part mediated by iron-dependent mechanisms.

Animals↗

Normal versus sickle red blood cells: hemodynamic and permeability characteristics in reperfusion lung injury.

Decreased deformability and increased internal viscosity of the sickle red blood cell (SRBC) contribute to abnormal flow in the microcirculation. Since the lungs are commonly affected in sickle cell disease, we compared the hemodynamics of the normal human red blood cell (NRBC) with the SRBC in the pulmonary circulation. The SRBC has decreased antioxidant enzyme activities compared with the NRBC. Thus, using the capillary filtration coefficient (Kfc), we determined the ability of the NRBC and the SRBC to attenuate the increased permeability and resulting edema seen in the oxidant stress of reperfusion lung injury (RLI). We found that lungs perfused with a 5% SRBC perfusate had higher pulmonary arterial pressures (Ppa) and resistances than lungs perfused with a 5% NRBC perfusate. Lungs made ischemic and reperfused with a physiologic cell-free perfusate resulted in a significant increase (P less than .05) in Kfc compared with the preischemic Kfc (.45 +/- .06 to 1.4 +/- 22 mL.min-1.cm H2O.100 g-1). In lungs reperfused with 5% RBC-containing perfusates, the Kfc did not change from preischemic Kfc with NRBCs and decreased from the preischemic Kfc with SRBCs. These findings suggest that the SRBC causes physiologically significant increases in Ppa and resistances and the SRBC, like the NRBC, offers apparent protection in RLI.

Anemia, Sickle Cell↗

Vasopressin-induced pulmonary vasodilation in rats.

Experiments were performed to determine the pulmonary vascular responses to exogenous or endogenous arginine vasopressin (AVP) in rats. Both in vitro and in vivo approaches were used to examine the direct pulmonary vasoactive properties of AVP and how those properties affect pulmonary hemodynamics in the intact animal. In conscious, unrestrained rats, constant infusion of AVP (4.0 mU.kg-1.min-1 iv) resulted in a fall in mean pulmonary artery pressure (PAP), although systemic pressure was increased. Coincident with the fall in PAP were similar reductions in cardiac output and heart rate. Similarly, bolus administration of AVP reduced PAP, and this effect was augmented during hypoxia. Another series of experiments examined the effect of endogenous AVP released by arterial hypoxemia on pulmonary hemodynamics in conscious rats. Administration of a specific V1-vasopressinergic antagonist had no effect on the PAP response to hypoxia; however, systemic resistance tended to fall following V1-antagonism. To determine the vasoactive properties of AVP independent of these changes in blood flow, a series of experiments were performed on isolated, perfused rat lungs. Injection of 25, 200, or 2,000 mU of AVP into the circulation of the isolated lung was without effect under normoxic conditions. In contrast, 25 mU AVP elicited reproducible pulmonary vasodilation when injected during ongoing hypoxic pulmonary vasoconstriction. This vasodilatory response was unaffected by meclofenamate or by the platelet-activating factor receptor antagonist SRI 63-441, but was blocked by a specific V1-vasopressinergic antagonist. We conclude that although AVP exerts profound systemic vasoconstriction, the pulmonary circulation appears relatively unaffected by exogenous or endogenous AVP in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

Failure of prediction of liver function test abnormalities with the urine urobilinogen and urine bilirubin assays.

A prospective observational study of 229 cases was conducted in a busy ambulatory care setting to evaluate the sensitivity, specificity, predictive values, and accuracy of spot urine urobilinogen and urine bilirubin assays as screening tests for serum liver function test (LFT) abnormalities. Both urine tests exhibited remarkably similar characteristics overall once they were adjusted to maximize accuracy and predictive values (occurring at a normal or abnormal "threshold," respectively, of 3.4 or 5.07 mumol/d for urobilinogen and 0 or 1+ for urine bilirubin). The percentage of cases correctly identified were 81% to 83% for serum bilirubin assays, 68% to 72% for other LFTs, but only 62% to 63% for screens for cases with at least one abnormal LFT finding. Poor sensitivities (47% to 49%) limited the detection of abnormal findings by the screen; both screens were reasonably specific (79% to 89%), but negative predictive values were suitable (89%) for serum bilirubin results only and were prohibitively lower (49% to 50%) in predicting all patients without LFT abnormalities. We conclude that spot urine urobilinogen and urine bilirubin determinations, although good screens for isolated serum bilirubin elevations, have unacceptable statistical properties as predictors of other LFT results due to a high proportion of false-negative results.

Bilirubin↗

Abnormalities of urine urobilinogen and urine bilirubin assays and their relation to abnormal results of serum liver function tests.

A prospective observational study of 324 cases was conducted in a busy ambulatory care setting to evaluate the sensitivity, specificity, predictive values, and accuracy of spot urine urobilinogen and urine bilirubin assays as screening tests for serum liver function test (LFT) abnormalities. High positive predictive values (88% for at least one abnormal LFT) make the evaluation of positive urine screens detected during routine health care maintenance examinations imperative. Because extraneous factors may influence both urine and serum test results, however, urine assays obtained as a screening parameter in clinical presentations (abdominal pain, jaundice, constitutional symptoms, etc) have only limited clinical utility. The high proportion of false-negative results for both urine assays renders their statistical properties unacceptable as screens in these clinical situations.

Adolescent↗

Alpha 1-and alpha 2-adrenoceptors of the circular myometrium from the dioestrous guinea-pig.

1. In order to investigate the nature of the alpha-adrenoceptors mediating contraction of circular myometrium from dioestrous guinea-pigs, the effects of several adrenoceptor antagonists upon log concentration curves to noradrenaline and phenylephrine have been examined. 2. In the presence of ICI 118,551 and nisoxetine both phenylephrine and noradrenaline produced concentration-dependent contractures of circular myometrium from virgin dioestrous guinea-pigs. Noradrenaline was the more potent and produced larger maximal contractions. Indomethacin (1 mumol/l) decreased the maximum effects of phenylephrine but not those of noradrenaline. Xylazine produced indomethacin-sensitive contractions which were not dose-related and which never exceeded 40% of those evoked by noradrenaline. Responses to xylazine and to noradrenaline, but not those to phenylephrine, were reduced in a low calcium solution. 3. Prazosin produced competitive antagonism of the effects of phenylephrine upon preparations of circular myometrium from virgin and parous dioestrous animals; pA2 values were both 8.1. Phentolamine also competitively antagonized the effects of phenylephrine (virgin animals, pA2=7.7). 4. Both prazosin and phentolamine antagonized the effects of noradrenaline upon preparations from virgin dioestrous animals, however, Schild plot analysis did not indicate a simple bimolecular interaction between agonist and receptors. In the presence of prazosin the alpha 2-adrenoceptor antagonist idazoxan produced dose-dependent parallel shifts in the positions of the log concentration-response curves to noradrenaline; the pA2 was 7.7. In the presence of idazoxan or of indomethacin prazosin competitively antagonized the effects of noradrenaline; the pA2 values were 8.5 and 8.2 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Platelet-activating factor antagonists increase vascular reactivity in perfused rat lungs.

Platelet-activating factor (PAF) administered to the pulmonary circulation in low dose (nanogram) has vasodilatory properties. Therefore, we investigated whether endogenous PAF plays a role in the control of tone in the pulmonary circulation. The PAF receptor antagonists, SRI 63-441 (2.6 X 10(-4) M) and L659,989 (1 X 10(-5) M), were the major investigative tools. In isolated perfused rat lungs, both agents caused a persistent increase in base-line perfusion pressure (Ppa), potentiated angiotensin II (ANG II) vasoconstriction, and potentiated hypoxic vasoconstriction (HPV). This potentiation of ANG II and HPV was found to be independent of circulating blood elements. Vasodilation in the presence of PAF blockade was also impaired. The combination of cyclooxygenase inhibition and PAF receptor blockade had an additive effect on ANG II vasoconstriction but did not cause more potentiation of HPV than achieved with PAF antagonism alone. In vivo, SRI 63-441 (10 mg/kg) caused only a transient increase in base-line Ppa without altering ANG II and hypoxic vasoconstriction. These findings support a vasodilatory role for endogenous PAF in the pulmonary circulation.

Angiotensin II↗

An outbreak of puerperal fever caused by group G streptococci.

An outbreak of puerperal fever caused by group G streptococci is described. Transmission of the organism may have occurred via contamination of automated douches. When these were disinfected and kept free of the organism the outbreak ended abruptly.

Adult↗

In vitro susceptibility of Capnocytophaga species to antimicrobial agents.

A total of 33 clinical isolates of Capnocytophaga spp. were susceptible to 4-quinolone antimicrobial agents. The antipseudomonal penicillins tested were equally active against all isolates, as were cefuroxime, ceftriaxone, ceftizoxime, cefotaxime, latamoxef, and ceftazidime. Most isolates were resistant to trimethoprim, and some were resistant to aztreonam. Most regimens for the empirical treatment of septic episodes in immunocompromised patients are suitable for the treatment of Capnocytophaga spp. infections.

Anti-Bacterial Agents↗

Electrohydraulic lithotripsy of gall stones--in vitro and animal studies.

Electrohydraulic lithotripsy of human gall stones was investigated in vitro in a bath of saline and in a saline perfused bile duct. The technique was effective--only two stones could not be shattered. Electrohydraulic lithotripsy power requirement correlated with mechanical strength of stones, but not with biochemical composition. A trend toward higher power requirement was recorded with larger stones and stones over 2 cm in diameter could not be fragmented. Safety studies indicated that electrohydraulic lithotripsy was safe, provided the probe tip was not in contact with the bile duct wall. In vivo studies did not show any late effects after 10 days. Electrohydraulic lithotripsy is likely to be useful in the management of biliary calculi.

Animals↗

Pulmonary edema. Complication in the management of sickle cell pain crisis.

Over a 12-month period, there were 51 admissions for sickle cell pain crisis. Of these, the course of four patients (two with hemoglobin SS, one with hemoglobin SC, and one with hemoglobin S-Thal) was complicated by the development of pulmonary edema. Pulmonary edema complicating the management of sickle cell pain crisis has not previously been described. Vigorous fluid replacement with hypotonic saline and parenteral narcotic analgesics are conventional modalities of therapy, but may contribute to the development of pulmonary edema. Narcotic analgesics causing increased permeability are well established. In pulmonary vascular beds predisposed to injury, hypotonic saline administration causing an increased hydrostatic pressure and decreased oncotic pressure may further compound pulmonary edema development. On the basis of the experience in this study, a conservative approach to the use of fluid administration and narcotic analgesics is advised.

Adult↗

Ambulatory esophageal pH monitoring in children as an indicator for surgery.

Twenty-four-hour esophageal pH monitoring was performed in 59 children with symptoms of gastroesophageal reflux using a miniature pH electrode and a portable recording system to establish the diagnosis. Significant reflux was seen in 26 (44%) of the patients and these were treated for six weeks with cimetidine, Gaviscon, and Nestargel. Five children who did not improve either symptomatically or on repeat pH monitoring while on treatment underwent antireflux surgery. The pretreatment reflux index in this group was 26.5 compared with a pretreatment reflux index of 11.2 in the 21 patients who improved on therapy (P less than 0.01). Esophageal pH monitoring has enabled selection of children for surgery and may be used as an early indicator of those who will not benefit from long-term medical therapy. Ambulatory and home monitoring techniques are more convenient and cost-effective and allow studies to be performed in the normal home environment.

Antacids↗