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Biomedical subjects

J O'Brien

Publications and source records attributed to J O'Brien.

At least 235 records · Page 13Linked to original sources
PubMed1985

Acylmorphinans. A novel class of potent analgesic agents.

A series of novel 2- and 3-acylmorphinans (8-14) was synthesized in our search for a potent analgesic agent with low addiction potential. The compounds were evaluated for antinociceptive potency and receptor binding affinity. Among these compounds, the levorotatory 3-acetyl-N-(cyclopropylmethyl)morphinan (12) was found to be an orally active analgesic, comparable in potency to morphine (1), yet only weakly able to substitute for morphine (1) in morphine-dependent rats.

Analgesia↗
PubMed1985

T-cell chronic lymphocytic leukaemia: anomalous cell markers, variable morphology, and marked responsiveness to pentostatin (2'-deoxycoformycin).

4 men with an unusual variant of T-cell chronic lymphocytic leukaemia are reported. The clinical features differed from the virus-associated T-cell disease reported from Japan, the Caribbean, and the southeastern United States. Cytology was pleiomorphic: cells with cerebriform nuclei resembling Sézary cells and lymphocytes with cytoplasmic granules resembling T-suppressor cells occurred in the same patients. Immunofluorescence studies with monoclonal antibodies suggested that the leukaemia cells expressed determinants of both helper- (OKT4+) and suppressor-(OKT8+) related antigens. The cells were TdT-negative. In all patients the disease was very refractory to conventional cytotoxic agents, but there was prompt and extensive response to the adenosine deaminase inhibitor pentostatin (2'-deoxycoformycin). This agent merits further study in the treatment of T-cell chronic lymphocytic leukaemia.

Adult↗
PubMed1985

Use of adjuvants for enhancement of rectal absorption of cefoxitin in humans.

The biological availability of cefoxitin administered rectally in the form of suppositories was examined in six human subjects by a cross-over design. Four different suppository systems containing adjuvants expected to enhance the absorption of the drug were studied. The presence of sodium salicylate and a nonionic surface-active agent, Brij 35, gave increased bioavailability as high as 20% compared with 3% for a system without adjuvants. The quantity of sodium salicylate was found to have an influence on the quantity of cefoxitin absorbed, and the salicylate was absorbed over an extended period of time from the rectum. The suppositories were well tolerated, and there were no adverse effects on bowel flora.

Biological Availability↗
PubMed1985

Effects of anthrax toxin components on human neutrophils.

The virulence of Bacillus anthracis has been attributed to a tripartite toxin composed of three proteins designated protective antigen, lethal factor, and edema factor. The effects of the toxin components on phagocytosis and chemiluminescence of human polymorphonuclear neutrophils were studied in vitro. Initially, it was determined that the avirulent Sterne strain of B. anthracis (radiation killed) required opsonization with either serum complement or antibodies against the Sterne cell wall to be phagocytized. Phagocytosis of the opsonized Sterne cells was not affected by the individual anthrax toxin components. However, a combination of protective antigen and edema factor inhibited Sterne cell phagocytosis and blocked both particulate and phorbol myristate acetate-induced polymorphonuclear neutrophil chemiluminescence. These polymorphonuclear neutrophil effects were reversible upon removal of the toxin components. The protective antigen-edema factor combination also increased intracellular cyclic AMP levels. These studies suggest that two of the protein components of anthrax toxin, edema factor and protective antigen, increase host susceptibility to infection by suppressing polymorphonuclear neutrophil function and impairing host resistance.

Anthrax↗
PubMed1985

Extra intestinal influences on exhaled breath hydrogen measurements during the investigation of gastrointestinal disease.

During the clinical investigation of patients with gastrointestinal disease by exhaled breath hydrogen measurement, the occurrence of inexplicable variations in recorded hydrogen values led to a search for extra intestinal factors which were capable of adversely influencing breath hydrogen concentration and impairing the diagnostic accuracy of the test. Serial breath samples were collected from normal subjects under a variety of conditions which might occur during routine clinical study, including, hyperventilation, exercise, cigarette smoking, and carbohydrate ingestion. Breath hydrogen concentrations were consistently reduced by hyperventilation (p less than 0.01) and exercise (p less than 0.05). Cigarette smoking, in contrast, caused a marked rise in measured breath hydrogen (p less than 0.01), as did oral carbohydrate (p less than 0.05). Prior bactericidal mouthwash abolished this carbohydrate associated rise, suggesting that the hydrogen was the result of fermentation by oropharyngeal bacteria. Because, in all instances, the changes in breath hydrogen were of sufficient magnitude to interfere with data interpretation, it is recommended that these factors are eliminated, whenever possible, from conditions of study.

Bacteria, Anaerobic↗
PubMed1985

Inhibition of rat liver glutathione S-transferases by piriprost: kinetics of the inhibition and preliminary evidence that piriprost may be a poor alternative substrate for these enzymes.

The administration of tritiated piriprost, an inhibitor of leukotriene formation, to rats resulted in its rapid excretion. Some 90 percent of the initial dose was excreted in the feces and only five to six percent were recovered in the urine, regardless of the route of administration of the compound. The finding of significant, though low, residual activity in the liver even seven days after dosing (0.016 and 0.072% of dose in orally and iv-treated animals, respectively) suggested that piriprost may be bound by proteins in liver which play a role in detoxification. The finding that piriprost is a potent inhibitor of several partially purified cytosolic liver glutathione S-transferases ( EC 2.5.1.18) is consistent with this suspicion. Kinetic studies indicate that the inhibition may be competitive with the chromogenic substrate, chloro-2,4-dinitrobenzene (Ki 1-2 microM) and non-competitive with respect to glutathione when the second substrate was present at saturating concentration. Incubation of one to four micromolar radiolabeled tritiated piriprost with glutathione resulted in the gradual formation of a series of products which could be detected by high pressure liquid chromatography. The formation of these products was stimulated by the presence of glutathione S-transferase although the same products were also formed in the absence of the enzyme.

Animals↗
PubMed1984

Dipyridamole-thallium-201 scintigraphy in the prediction of future cardiac events after acute myocardial infarction.

To evaluate the safety and usefulness of serial thallium scanning immediately after intravenous dipyridamole, we studied 51 patients recovering from acute myocardial infarction. Eight patients experienced angina during the procedure, but there were no serious complications. Patients were followed for a mean period of 19 months after hospital discharge. Eleven of 12 patients who died during follow-up or had another infarction had shown transient defects (redistribution) on their predischarge scan, as had 22 of the 24 patients who needed readmission for management of angina. Among all the other clinical or scintigraphic criteria tested, the presence of redistribution on the dipyridamole-thallium scan was the only significant predictor of these serious cardiac events. Twenty-six patients were also given a submaximal exercise test before discharge, of whom 13 subsequently had serious cardiac events. The exercise test had been positive in only 6 of these 13 patients, whereas the dipyridamole-thallium scan had shown a redistribution pattern in 12 (P less than 0.001). We conclude from this preliminary study that dipyridamole-thallium scintigraphy after myocardial infraction is relatively safe. It appears to be a more sensitive predictor of subsequent cardiac events than a submaximal exercise test and may therefore prove useful in evaluating patients after recovery from a myocardial infarction.

Aged↗
PubMed1984

The effect of glucagon on urine amylase in various animal species.

Glucagon effects on the kidney include increased water, creatinine, and amylase clearance. We have compared these effects in several laboratory animal species. Although every species responded to glucagon, 1 mg iv, by some alteration in renal function there were differences in the degree and direction of the changes. Glucagon caused an increase in amylase clearance in four of the six species studied and an increase in creatinine clearance in four. An increase in urine flow tended to occur in all species. An increased amylase clearance is a feature of acute pancreatitis, and raised glucagon levels have been found during attacks. It is possible that the two are causally related. In the experimental situation, timing of urine collections and species differences were found to be of critical importance in exploring this possibility.

Amylases↗
PubMed1984

Amylase excretion after exercise.

Increase in amylase excretion in the urine in response to 8 days of aerobic running is delayed until after the athletes have rested for 24-48 h. In contrast, the amylase creatinine ratio is increased immediately after intense short-term exercise. The mechanism for these differences is unknown, but the timing of the amylase excretion pattern after long- and short-term exercise is similar to the urinary amylase after continuous and single bolus intravenous glucagon.

Amylases↗
PubMed1982

Role of veiled cells in lymphocyte activation.

Peripheral blood lymphocytes from normal rabbits or from rabbits hyperimmunized with human immunoglobulin were cultured in 20-microliters hanging droplets. The cultures were stimulated with concanavalin A or, in the case of cells from sensitized animals, with human immunoglobulin. The addition to the cultures of small numbers of autologous or allogeneic veiled cells separated from afferent lymph increased the responses to low doses of the stimulants, particularly when the cells were cultured at low cell densities or for short periods of time. At high cell densities or at longer periods of culture, stimulation occurred in the absence of added veiled cells and was associated with clumping of the lymphoid cells and development of cells which morphologically resembled veiled cells found in afferent lymph. The enhanced responses upon addition of small numbers of veiled cells were also correlated with the formation of lymphoid aggregates which were frequently held together by the elongated processes of a single veiled cell. The observations support the view that the veiled cells are lymph-borne precursors of dendritic cells in the lymph nodes. This may provide an in vitro model for the cellular relationships which occur in paracortical cords of lymph nodes following antigenic stimulation.

Animals↗
PubMed1982

Assessing methods for measuring compliance with a fat-controlled diet.

This study assessed the relative validity of the following non-laboratory measures of compliance with a fat-controlled diet by hypercholesterolemic males: quantitative and qualitative measures of compliance derived from three-day food records and structured interviews, and summary ratings by nutritionists and interviewers. The quantitative measures of consumption referred to: saturated fat, linoleic acid, polyunsaturated fat, P/S ratio and cholesterol. The non-laboratory measures were assessed using the following two laboratory measures as criteria of validity: serum cholesterol concentration and the proportion of linoleic acid among the fatty acids of the serum cholesteryl esters. The results showed that, with respect to quantitative measures, the food record and interview manifested approximately equal validity, with the former marginally more valid. However, under certain conditions qualitative measures, such as patients' self-ratings, were about as valid as the more rigorous and expensive quantitative measures. Characteristics of the patient influenced the validity of the various measures. Validity was enhanced by the simultaneous use of certain combinations of measures.

Adult↗