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J Flynn

Publications and source records attributed to J Flynn.

At least 109 records · Page 6Linked to original sources
PubMed1984

Role of oxygen radicals in endotoxin-induced lung injury.

We tested the hypothesis that the increased permeability in the pulmonary microcirculation seen with endotoxin is caused by the release of oxygen radicals from activated neutrophils. We first compared the pulmonary injury in sheep caused by low-dose endotoxin with that produced by phorbol myristate acetate, an agent that selectively causes the release of oxygen radicals from neutrophils. We then determined the degree of lung tissue lipid peroxidation, a reflection of direct oxygen radical damage after endotoxin and phorbol myristate acetate. Both agents produced a nearly identical increase in protein permeability; however, peroxidation was only evident with phorbol myristate acetate. Higher doses of endotoxin did result in increased lung peroxidation as well as a more severe physiologic injury. We can conclude that oxygen radical release, most likely from neutrophils, occurs with endotoxin. However, the permeability injury may not be the direct result of increased lipid peroxidation, as increased permeability can be seen without measurable increases in this parameter.

Animals↗
PubMed1984

Catechol derivatives of 6-aminobenzocycloheptene: assessment of dopaminergic effects.

The title compounds were prepared as congeners of the dopaminergically potent 2-amino-5,6-dihydroxytetralin series ("A-5,6-DTN"). None of the variously nitrogen-substituted benzocycloheptenes demonstrated any dopamine-like effects in a variety of assays. The primary amine had alpha 1-adrenoceptor stimulant effects. This lack of dopaminergic effect parallels the inactivity found in 6-aminobenzocycloheptenes bearing no oxygen substitutents, those bearing a single phenolic group, and those bearing a resorcinol 1,3-diphenolic substitution pattern.

Animals↗
PubMed1984

Structure activity relationships of resorcinol substituted ring systems.

Dopamine receptor agonist activity was evaluated using resorcinol derivatives of the following ring systems: dopamine, aminotetralin, indan, benzocycloheptane, octahydrobenzo(f)quinoline and octahydrobenzo[g]quinoline. The compounds were evaluated for biological activity using in vitro binding assays, anesthetized cat blood pressure and heart rate, cat cardioaccelerator nerve preparation and rotations of rats with unilateral denervation of the caudate nucleus. Resorcinol substitutions were chosen because one hydroxyl group corresponded to the alpha-conformer of dopamine and the second hydroxyl group corresponded to the beta-conformer of dopamine. Dopamine receptor activity was found primarily with derivatives of aminotetralin and octahydrobenzo[f]quinoline while the other ring systems yielded compounds which were quite inactive. The active resorcinol derivatives were found in the same ring systems where catechol substitution was active in ring positions corresponding to either the alpha- or beta-conformer of dopamine. Likewise in those ring systems where catechol substitution corresponding to the beta-conformer of dopamine were quite inactive, resorcinol substitution in these series was not favorable for activity. The ring systems requirements for alpha- and beta-adrenoceptor agonist activity did not follow the same structural pattern as found for dopamine receptor agonist activity.

Animals↗
PubMed1984

TL-350, an ergoline derivative with dopamine receptor agonist properties.

Intravenous and intraduodenal injection of a new ergoline derivative, TL-350, produced dose-dependent inhibition of heart rate increase produced by cardioaccelerator nerve stimulation in anesthetized cats. ID50 values of TL-350 were 0.019 and 0.047 mumol/kg after i.v. and intraduodenal injection, respectively. This inhibition was reversed by either sulpiride (0.15 mumol/kg i.v.) or haloperidol (0.13 mumol/kg i.v.) but not by yohimbine (0.14 mumol/kg i.v.). TL-350 did not change isoproterenol-induced tachycardia and hypotensive responses. TL-350 caused dose-dependent decrease of arterial blood pressure and heart rate in anesthetized cats. Haloperidol (0.13 mumol/kg i.v.) prevented the hypotensive and bradycardic effects of the compound. TL-350 also produced concentration-dependent inhibition of heart rate responses to transmural stimulation of isolated cat right atria. IC50 value was 0.026 microM. Dopaminergic antagonists, haloperidol and sulpiride, antagonized the inhibitory effect of TL-350 in in vitro experiments. TL-350 did not stimulate presynaptic alpha-2 adrenergic receptors in rat vas deferens and guinea-pig ileum. TL-350 induced rotation for 3 hr in rats with unilateral denervated caudate nucleus. The compound was 0.5 as potent as apomorphine. In [3H]dopamine binding assays using rat caudate tissue, TL-350 had approximately the same activity as apomorphine in displacing the radioligand. It was concluded that TL-350 is a selective dopamine receptor agonist without possessing alpha and beta adrenergic receptor stimulating activity.

Animals↗
PubMed1983

Indomethacin improvement of septic acute respiratory failure in a porcine model.

The effects of indomethacin, a prostaglandin synthesis blocker, were tested in a porcine model of septic acute respiratory failure (ARF) produced by continuous infusion of live Ps. aeruginosa. Control groups received either indomethacin boluses (2 mg/kg) intravenously at 20 and 210 minutes or Ps. aeruginosa infusion (2 X 10(8) CFU/20 kg/min). The treatment group received both continuous Ps. aeruginosa infusion and indomethacin. Indomethacin alone transiently but significantly decreased cardiac indices, heart rate, and PaCO2. With Ps. aeruginosa infusion, significant pulmonary hypertension, hypoxemia, increased intrapulmonary shunt fraction, and systemic hypotension occurred. In this porcine model of septic ARF, indomethacin doubled the survival period and improved cardiopulmonary parameters.

Acute Disease↗
PubMed1983

Effect of thermal injury on endotoxin-induced lung injury.

We studied the effects of a burn injury on the response of the lung to endotoxin. Seventeen unanesthetized sheep with lung lymph fistulas were studied. Eight were given Escherichia coli endotoxin (1.5 micrograms/kg) alone and nine were given the same dose 72 hours after a 25% total body surface burn injury. At this time after burn, all physiologic parameters were at baseline levels. A characteristic two-phase lung injury was seen after administration of endotoxin with an initial hypertension phase, characterized by pulmonary artery hypertension, and a second or permeability phase, characterized by an increase in protein-rich lymph flow. all eight animals that underwent only endotoxin administration survived, whereas four of the nine burned animals died during the permeability phase in pulmonary edema. Major physiologic differences between the groups were noted during the permeability phase, including a more severe hypoxia, pulmonary hypertension, and increased postburn lymph flow. Major biochemical changes included significant increases in lymph thromboxane, thromboxane B2, and beta-glucuronidase activity in the burn group. We conclude that the lung is more sensitive to endotoxin after burn, probably as a result of an increased release of products of arachidonic acid metabolism and products of leukocyte activation caused by the body burn.

Animals↗
PubMed1982

OPEC otitis.

Explore the source record for details and available documents.

Adult↗
PubMed1982

Structure activity relationships of presynaptic dopamine receptor agonists.

Structure activity relationship (SAR) studies have identified many structural entities that interact with dopamine receptors. The aminotetralin structure may be regarded as an active moiety of apomorphine. An unanswered question concerns the SAR of the 4,7-dimethoxy indane derivatives. These agents do not appear to match well with models of dopamine receptors. At least there can be little doubt that SAR research has been a powerful stimulus during the past decade for understanding the function, distribution, and spatial aspects of dopamine receptors.

Animals↗
PubMed1982

Bone metabolism in chronic renal failure.

Quantitative bone histology was carried out on 37 haemodialysis patients. Hyperparathyroid bone disease (HPT) was diagnosed by an elevated osteoclast count, and high counts were associated with classic osteitis fibrosa. Osteomalacia (OM) was found in two distinct though frequently overlapping forms, both with increased osteoid surface. In classic OM (type 1), present in 19% of patients the osteoid seams were wide and the mineral apposition rate low, with the tetracycline bands wide and merging together. In the more common form of OM (type 2), present in 81%, the mineralising surface, as shown by tetracycline uptake, was reduced, but the mineral apposition rate was normal. Tetracycline surface was highly correlated with osteoblast surface, suggesting that osteoblasts play a role in mineralisation, and that type 2 OM is caused by a reduction in osteoblast surface. The osteoblast surface also correlated with serum parathyroid hormone, and so secondary hyperparathyroidism may obscure the diagnosis of type 2 OM, which may be almost universally present in haemodialysis patients. Type 1 OM is not obscured by secondary hyperparathyroidism. Of the 37 patients 5 had HPT, 9 OM and 22 HPT + OM. Only one had normal bone. Biochemical parameters had limited predictive value. The study also did not support the suggestion that endogenous calcitonin protects against HPT disease.

Adult↗
PubMed1981

Rare complications following ethmoidectomies: a report of eleven cases.

Intranasal ethmoidectomy is one of the most difficult operations to teach residents. An accurate knowledge of the regional topographic anatomy is of utmost importance. Friedman and Kerr reported complications of 1000 cases of consecutive intranasal ethmoidectomies performed at the Mayo Clinic from 1957 to 1972. The complication rate was 2.8%. Meningitis, cerebrospinal fluid rhinorrhea, loss of olfaction, and nasolacrimal duct obstruction were reported. No blindness, loss of occular motility, excision of brain tissue or intracranial vessel damage occurred in their series. We are reporting a series of 8 cases of very rare complications following intranasal ethmoidectomies: 1. Optic nerve damage resulting in total blindness (3 cases). 2. Loss of occular motility (2 cases). 3. Cerebrospinal fluid leak resulting in 8 episodes of pseudomonas meningitis and epidural abscess (1 case). 4. Cavernous sinus--internal carotid artery fistula (1 case). 5. Anterior cranial fossa brain damage resulting in death (1 case). These cases, which were either referred to us or came up for our review, are described in detail. A search of the world literature demonstrates a lack of emphasis on such complications. The pitfalls of intranasal ethmoidectomy are considered and ways to avoid such dreadful complications are discussed.

Adult↗
PubMed1981

Pulmonary microvascular injury from lipoxygenase infusion: comparison with endotoxemia.

We compared the response of the pulmonary microcirculation to a 5-hr infusion of soybean lipoxygenase with that seen after endotoxin. We monitored microvascular integrity using lung lymph flow QL and lymph/plasma (L/P) protein ratio in unanesthetized sheep. We noted a twofold to threefold increase in QL and a slight decrease in L/P ratio beginning about 1 hr after onset of the lipoxygenase infusion. Leukocyte count decreased significantly and lymph lysosomal enzyme activity increased. Pulmonary artery pressure initially increased from 16 to 31 mm Hg, then decreased to 25 mm Hg during continued infusion. Platelet count remained constant. Parameters returned to baseline several hours after infusion. This pulmonary vascular pressure and lymph flow response was very similar to that seen in the increased permeability phase of endotoxin. A decrease on the L/P ratio and a constant rather than a decreased platelet count were findings different from those seen after endotoxin.

Animals↗
PubMed1981

The effect of prostacyclin infusion on endotoxin-induced lung injury.

Lung injury produced by endotoxin is characterized by both pulmonary hypertension and increased pulmonary vascular permeability. Prostacyclin (PGI2) has been found to be a vasodilator and a membrane stabilizer. The purpose of this study was to determine the effectiveness of PGI2 in preventing endotoxin injury. Eight sheep with chronic lung lymph fistula were given both Escherichia coli endotoxin (2 microgram/kg) alone and endotoxin plus an immediate infusion of PGI2 (0.1 to 0.2 microgram/kg/min) for a 5-hour period; the studies were performed 4 days apart. The endotoxin injury was characterized by early severe pulmonary hypertension, with pulmonary artery pressure increasing from 18 +/- 0.6 to 40 +/- 3.1 mm Hg and lung lymph flow (QL) increasing threefold. This was followed in about 3 hours by an increase in permeability characterized by an increasing lymph to plasma protein ratio (0.63 to 0.74) and a threefold increase in QL. In seven of eight animals infused with PGI2 the pulmonary hypertension and alteration in QL in the early and later phases were significantly decreased. In four paired studies, prostaglandins PGE, PGF2 alpha, and PGI2 as 6-keto PGF1 alpha were measured in lymph and plasma. PGF2 alpha and PGI2 were significantly increased in lung lymph during the early hypertensive phase immediately after endotoxin injection, but returned to baseline during the later phase. In the PGI2 infusion studies, PGF2 alpha showed the same pattern of response, but PGI2 was increased to much higher levels in lymph and plasma, as compared to values of endotoxin alone. The higher plasma values corresponded with less severe lung injury. The one animal not protected by PGI2 had the lowest plasma PGI2 level. We therefore found PGI2 to protect the lung against injury from endotoxin.

Animals↗
PubMed1981

Leukocytes, platelets, and thromboxane A2 in endotoxin-induced lung injury.

The relationship of leukocytes, platelets, and thromboxane A2 (TxA2) to endotoxin-induced lung injury was studied by use of chronic pulmonary lymph fistula in 12 adult female sheep. Endotoxin-induced lung injury in sheep was characterized by an early pulmonary hypertensive phase followed by a phase of increased capillary permeability. A profound leukopenia occurred early after endotoxin infusion and persisted during both phases of the injury. TxA2 levels (measured as its metabolite thromboxane B2) were significantly increased during the hypertensive phase and then returned rapidly to baseline. Levels were higher in lymph than in plasma, implying local generation in lung. Platelet count decreased transiently later in the permeability phase, rapidly returning toward baseline in animals that survived. The decrease in platelets occurred after TxA2 levels had returned to baseline, suggesting that TxA2 may be coming from sources other than platelets. We conclude that leukocytes appear to play a major role in initiating endotoxin-induced lung injury, and TxA2 may be contributing to pulmonary hypertension. Platelets, on the other hand, seem to be transiently sticking to an already damaged endothelium, with the degree of sequestration indicative of the severity of the injury.

Animals↗
PubMed1980

Giardiasis in infancy diarrhoea.

Of 435 infants with diarrhoea aged under one year, 6% were found to have Giardia lamblia; the incidence ranged from 3% housed infants to 12% in itinerant infants. All infants had duodenal fluid and faeces examined. Infants under 12 weeks may experience severe diarrhoea in association with infection by this parasite, but seem more likely to respond to metronidazole than older infants.

Diarrhea, Infantile↗