Image of interest. Hepatobiliary and pancreatic: hepatic artery aneurysm.
Explore the source record for details and available documents.
Aneurysm↗
Biomedical subjects
A Lord
Publications and source records attributed to A Lord.
The value of asthma camps for young people in Victoria, Australia.
PURPOSE: This paper investigates the impact of the Asthma Foundation of Victoria's educational camp program on children's knowledge of asthma and its management, their feelings about asthma, and their attitudes toward physical and social activities. Parents' observations of changes in their child's behaviour and attitudes are also reported. DESIGN AND METHODS: This research was descriptive and applied. It used questionnaires atfour stages (directly pre- and post-camp, three-four months and ten-15 months post-camp) of an asthma education camp program to assess child asthma knowledge levels. At three months post-camp, parental observations of children's attitudes and behaviours were assessed using a questionnaire. Children's feelings toward asthma were also assessed using a questionnaire pre- and post-camp. RESULTS: The children surveyed displayed a better knowledge of asthma and how to manage their condition immediately after the camp. This knowledge tended to return to pre-camp levels after ten months. The children also reported less anxiety and fear about their illness, a greater sense of wellbeing, and more confidence in participating in a whole range of physical and social activities. Many parents also noted positive changes in their children in terms of activities and asthma management at three months post-camp. CLINICAL IMPLICATIONS: Although there were limitations to sustaining knowledge gained in the asthma camping program, the camping experience provided a benefit for children in terms of promoting their mental and social wellbeing. When readers consider modernising asthma education (e.g. shorter camps, education in everyday social settings such as schools), they need to consider retaining the key ingredients of the more traditional camping program that supports good asthma management, wellbeing and social participation.
Adolescent↗
Impaired humoral responses to subgenus D adenovirusenovirus infections in HIV-positive patients.
HIV-positive patients are at increased risk of developing adenovirus infection, particularly of the gastrointestinal tract and with unusual subgenus D strains. To investigate humoral immunity to these strains of adenoviruses, the humoral immune response was examined in longitudinal samples of serum against isolates collected from a prospective study of HIV-positive patients with subgenus D adenovirus infection. Of 10 HIV-positive patients developing adenovirus infection, 3 had chronic infection (8->27 months) with one serotype, 3 had chronic infection (>/=10 months) with changing serotypes and 4 had acute and self-limiting adenovirus infection (<1 month). Fifty-one sera were tested, and samples collected before adenovirus infection were available in 8 patients. Neutralising assays were performed against the patient's own isolate (adenoviruses 9, 17, 19, 19/23, 19/37, 23, 26, 23/26, 43 and 46) and common circulating strains of adenovirus 1-5. Indirect immunofluorescence tests were carried out against the autologous isolate and complement-fixation tests were undertaken using a standard assay. Immunofluorescence test antibodies were detected (titre >/=160) in all patients, and present to high titre (>/=320) in 8/10 patients. Complement-fixing antibodies were not detected in significant titre. Of particular note, there was no significant neutralising antibody response to the patient's own isolate after acute infection. Neutralising antibody to adenovirus 3 (titre 20) was transiently detected in two patients. In the remaining patients neutralising antibody directed against adenoviruses 1-5 was not detected. Persistent carriage of subgenus D adenoviruses in HIV-positive patients is probably the result of failure of cell-mediated immune responses to clear primary infection. Nevertheless, there is marked impairment of B cell responses resulting in poor neutralising and complement-fixing antibody production even though immunofluorescence test determined antibodies are produced in high titre. These possibly reflect impairment of effective B cell priming mechanisms within the germinal centres of lymph nodes, or the polyclonal activation of B cells driven by HIV infection.
AIDS-Related Opportunistic Infections↗
"The Great Arcana of the Deity": menstruation and menstrual disorders in eighteenth-century British medical thought.
Explore the source record for details and available documents.
England↗
Cloning and analysis of the glucosyl transferase gene encoding type I antigen in Shigella flexneri.
The O-antigen of most Shigella flexneri serotypes contains an identical tetrasaccharide repeating unit. Apart from serotype Y, the O-antigen is modified by addition of a glucosyl and/or O-acetyl residue to a specific position in the O-unit. In this study the glucosyl transferase gene from a serotype 1 a has been cloned and identified. The bacteriophage SfV integrase (int) gene was used to probe a S. flexneri Y53 (serotype 1 a) cosmid library and 18 unique clones were identified. Southern hybridisation of these clones indicated two unlinked regions of the chromosome contained the int homologue. When expressed in a live candidate vaccine strain of S. flexneri serotype Y (SFL124), clones with one region produced type I antigen, whereas clones containing the other region produced mainly type Y antigen. One of the cosmid clones positive for type I antigen by agglutination and Western blotting was selected for further study. Genes involved in O-antigen glucosyl modification were mapped on a 5.8 kb fragment and subclones were produced which fully or partially expressed the type I antigen, depending on the extent of the clone. Fully and partially expressing clones may be useful vaccine candidate strains for protection against disease caused by two serotypes of S. flexneri.
Antigens, Bacterial↗
Pharmacology of montelukast sodium (Singulair), a potent and selective leukotriene D4 receptor antagonist.
Montelukast sodium (Singulair), also known as MK-0476 (1-(((1(R)-(3-(2-(7-chloro-2-quinolinyl)-(E)-ethenyl)phenyl)(3-2-(1- hydroxy-1-methylethyl)phenyl)propyl)thio)methyl)cyclopropane) acetic acid sodium salt, is a potent and selective inhibitor of [3H]leukotriene D4 specific binding in guinea pig lung (Ki 0.18 +/- 0.03 nM), sheep lung (Ki 4 nM), and dimethylsulfoxide-differentiated U937 cell plasma membrane preparations (Ki 0.52 +/- 0.23 nM), but it was essentially inactive versus [3H]leukotriene C4 specific binding in dimethylsulfoxide-differentiated U937 cell membranes (IC50 10 microM) and [3H]leukotriene B4 specific binding in THP-1 cell membranes (IC50 40 microM). Montelukast also inhibited specific binding of [3H]leukotriene D4 to guinea pig lung in the presence of human serum albumin, human plasma, and squirrel monkey plasma with Ki values of 0.21 +/- 0.08, 0.19 +/- 0.02, and 0.26 +/- 0.02 nM, respectively. Functionally, montelukast antagonized contractions of guinea pig trachea induced by leukotriene D4 (pA2 value 9.3; slope 0.8). In contrast, montelukast (16 microM) failed to antagonize contractions of guinea pig trachea induced by leukotriene C4 (45 mM serine-borate), serotonin, acetylcholine, histamine, prostaglandin D2, or U-44069. Intravenous montelukast antagonized bronchoconstriction induced in anesthetized guinea pigs by i.v. leukotriene D4 but did not block bronchoconstriction to arachidonic acid, histamine, serotonin, or acetylcholine. Oral administration of montelukast blocked leukotriene D4 induced bronchoconstriction in conscious squirrel monkeys, ovalbumin-induced bronchoconstriction in conscious sensitized rats (ED50 0.03 +/- 0.001 mg/kg; 4 h pretreatment), and also ascaris-induced early and late phase bronchoconstriction in conscious squirrel monkeys (0.03-0.1 mg/kg; 4 h pretreatment). A continuous i.v. infusion of montelukast (8 micrograms.kg-1.min-1) resulted in a 70% decrease in the peak early response and a 75% reduction of the late response to ascaris aerosol in allergic conscious sheep. Montelukast, a potent and selective leukotriene D4 receptor antagonist with excellent in vivo activity is currently in clinical development for the treatment of asthma and related diseases.
Acetates↗
Detrusor hyperreflexia--are there two types?
The concept that elderly patients with urinary incontinence due to detrusor hyperreflexia can be divided into two groups with differing natural histories on the basis of the detrusor contractility found on cystometry is reassessed. Thirty patients shown to have hyperreflexia on urodynamic study for persistent urinary incontinence following a recent neurological lesion had their contractility measured by the suggested criteria of the residual urine following a hyperreflexic contraction and the rate of increase of detrusor pressure. The consistency of contractility on cystometry was also measured by repeating this three times on the same occasion. A spectrum of values for the post-contraction volumes and the rate of increase of detrusor pressure was found. On repetitive cystometry 11 out of 30 patients showed a variable post-contraction residual volume. While impaired contractility is common in detrusor hyperreflexia, the concept of two subgroups is not supported by these results. In some patients cystometric measures of contractility vary considerably on repeating the study on the same occasion.
Aged↗
Characterization of specific binding sites for cysteinyl leukotrienes in sheep lung.
Specific binding sites for [3H]leukotriene (LT)D4 and [3H]LTC4 have been identified in sheep lung parenchymal membranes. [3H] LTD4 specific binding was of high affinity (KD = 0.56 nM), saturable (Bmax = 43 fmol/mg of protein), stimulated by divalent cations and inhibited by nonhydrolyzable GTP analogs. LTs and LTD4-receptor antagonists competed for [3H]LTD4 specific binding with the rank order of potency predicted for the LTD4 receptor: LTD4 > ONO-1078 > ICI 204,219 > MK-571 > LTE4 > LTC4 > BAY u9773 >> LTB4. In contrast, [3H]LTC4 specific binding was of lower affinity (KD = 27 nM), abundant (Bmax = 87 pmol/mg of protein) and although stimulated by divalent cations was unaffected by GTP analogs. LTs and LTC4 analogs competed for [3H]LTC4 specific binding with the following rank order of potency: LTC2 > LTC3 > LTC4 > LTC5 >> N-methyl-LTC4 >> LTD4 approximately LTB4 approximately LTB4. [3H]LTD4 specific binding to sheep lung membranes has, therefore, the characteristics of being to a G-protein-coupled LTD4 receptor, whereas the profile of [3H]LTC4 specific binding strongly suggests that these sites are not LT-receptor related. Photolabeling of sheep lung membranes using [125I]azido-LTC4, a photoactivable LTC4 analog, resulted in the selective photolabeling of two polypeptides migrating at 30 kDa and 19 kDa. The selective photolabeling of the 19 kDa polypeptide could be modulated in an identical manner to [3H]LTC4 specific binding. This protein is, therefore, a candidate for being the principal [3H]LTC4 specific site in sheep lung membranes and has a comparable molecular mass to microsomal glutathione S-transferase, recently shown to be the predominant LTC4 binding protein in cellular membranes.
Animals↗
Energy balance in healthy elderly women.
There is a paucity of data on which to base estimates of the energy requirements of the elderly. In general, ageing appears to be associated with a reduction in energy requirement arising from a reduction in physical activity and loss of fat-free mass. The aim of the present study was to measure the total energy expenditure (TEE), basal metabolic rate (BMR), and energy expended on physical activity (calculated as TEE-BMR) in a group of healthy elderly women living in the community in Southampton. Mean rates of TEE (9.21 (SD 1.48) MJ/d) and energy expended on physical activity (4.12 (SD 1.19) MJ/d) were higher than those observed in some studies of younger adults in the UK, and higher than the factors used to estimate the average energy requirement for the elderly. The results suggest that an age-related reduction in energy requirement is not inevitable and support the hypothesis that the effects of ageing on physical activity, body composition, and hence energy requirements, are variable.
Aged↗
The reflush effect--a prospective analysis of late perfusion.
This prospective randomized trial examines the effect of a "reflush" with preservation solution immediately prior to renal allograft implantation, using hyperosmolar citrate (HOC, n = 10) or phosphate-buffered sucrose (PBS140, n = 10) versus no reflush (n = 10). All kidneys had been stored in HOC. The HOC reflush did not alter the postpreservation intra- or extracellular electrolyte milieu, whereas the PBS140 reflush resulted in an apparent overall loss of both sodium and potassium from the kidney (P < 0.0005). A small amount of calcium was released into the venous effluent in both reflush groups. A similar amount of lactic acid was released into the venous effluent of the two reflush groups, reflected by a lower pH (P < 0.0005), and there was a similar loss of lactate dehydrogenase and creatine phosphokinase. An analysis of procoagulant activity in the first urine produced was performed as a marker of reperfusion injury. The median value was higher in the No Reflush group at 457.5 units, compared with 263.0 and 209.0 units for the PBS140 and HOC Reflush groups, respectively (P = 0.06). Reflushing the kidneys reduced the postoperative dialysis requirement (from 40% to 15%), but by the end of the first posttransplant week there was no significant difference between the renal functional analyses of the three groups, and there was no difference at one year. The proposed mechanism for the early renal functional improvement is a reduction in the calcium paradox and free radical formation, by release of calcium and ATP breakdown products into the venous effluent prior to implantation.
Adolescent↗
Pharmacology of the leukotriene antagonist verlukast: the (R)-enantiomer of MK-571.
Verlukast (MK-679) (3-[(3-(2-(7-chloro-2-quinolinyl)-(E)-ethenyl)phenyl)[3-(dimethylamino)- 3- oxopropyl)thio)methyl)-thio)propionic acid) is a potent and selective inhibitor of [3H]leukotriene D4 binding in guinea-pig (IC50 = 3.1 +/- 0.5 nM) and human (IC50 = 8.0 +/- 3.0 nM) lung homogenates and dimethyl sulfoxide differentiated U937 cell membrane preparations (IC50 = 10.7 +/- 1.6 nM) but is essentially inactive versus [3H]leukotriene C4 binding in guinea-pig lung homogenates (IC50 values of 19 and 33 microM). Functionally, when tested at 60 nM, it antagonized contractions of guinea-pig trachea (GPT) induced by leukotriene C4, leukotriene D4, and leukotriene E4 (respective-log KB values of 8.6, 8.8, and 8.9) and contractions of human trachea (HT) induced by leukotriene D4 (-log KB value 8.3 +/- 0.2). In contrast, verlukast (20-200 nM) failed to antagonize contractions of GPT induced by leukotriene C4 in the presence of 45 mM L-serine borate. Intravenous (i.v.) and aerosol verlukast antagonized bronchoconstriction (BC) induced in anaesthetized guinea pigs by i.v. leukotriene D4 but did not block BC to arachidonic acid or histamine. Intraduodenal verlukast (0.25 mg/kg) antagonized leukotriene D4 (0.2 micrograms/kg) induced BC in guinea pigs. Oral and aerosol administration blocked leukotriene D4-induced BC in conscious squirrel monkeys. Orally administered compound also blocked ovalbumin-induced BC in conscious sensitized rats treated with methysergide (3 micrograms/kg). The pharmacological profile for verlukast is similar to that of the racemic compound, MK-571. Verlukast is currently in clinical development for the treatment of asthma and related diseases.
Animals↗
Stereospecific synthesis, assignment of absolute configuration, and biological activity of the enantiomers of 3-[[[3-[2-(7-chloroquinolin-2-yl)-(E)-ethenyl]phenyl] [[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid, a potent and specific leukotriene D4 receptor antagonist.
The enantiomers of the leukotriene D4 antagonist 3-[[[3-[2-(7-chloroquinolin-2-yl)-(E)-ethenyl]phenyl] [[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid (L-660,711)(MK-571) have been prepared, their absolute stereochemistry has been assigned as S for (+)-1 and R for (-)-1 by X-ray analysis of a synthetic intermediate (5), and the biological activity of the enantiomers has been explored. Unexpectedly, the enantiomers are both comparably biologically active with (+)-1 slightly more intrinsically active at the LTD4 receptor in vitro.
Animals↗
Fractional conversion of thromboxane A2 and B2 to urinary 2,3-dinor-thromboxane B2 and 11-dehydrothromboxane B2 in the cynomolgus monkey.
Following the intravenous administration of thromboxane (TX) B2, the stable hydration product of TXA2, to human and nonhuman primates the most abundant urinary metabolites are 2,3-dinor-TXB2 and 11-dehydro-TXB2. However, it is not known whether fractional conversion of TXB2 to its enzymatic metabolites is an accurate representation of TXA2 metabolism. Thus, we have compared the metabolic disposition of synthetic TXA2 and TXB2 via the beta-oxidation and 11-OH-dehydrogenase pathways in vivo in the monkey. TXA2 or TXB2 (20 ng/kg) was intravenously administered to four cynomolgus monkeys pretreated with aspirin in order to suppress endogenous TXA2 production. Urinary TXB2, 2,3-dinor-TXB2 and 11-dehydro-TXB2 were measured before, during and up to 24 h after thromboxane administration by means of reversed-phase high-performance liquid chromatography radioimmunoassay. Aspirin treatment suppressed urinary 2,3-dinor-TXB2 and 11-dehydro-TXB2 by approx. 75%. A similar fractional conversion of TXA2 and TXB2 into 2,3-dinor-TXB2 and 11-dehydro-TXB2 was found. These results suggest that TXA2 is hydrolyzed to TXB2 prior to enzymatic degradation and that metabolites of the latter represent reliable indices of TXA2 biosynthesis. Due to the variability in the conversion of thromboxanes into 2,3-dinor-TXB2 and 11-dehydro-TXB2, the measurement of both metabolites seems to represent a more reliable index of acute changes in TXA2 production.
Animals↗
The pharmacology of L-670,596, a potent and selective thromboxane/prostaglandin endoperoxide receptor antagonist.
L-670,596 ((-)6,8-difluoro-9-rho-methylsulfonyl benzyl-1,2,3,4- tetrahydrocarbazol-1-yl-acetic acid) has been shown to be a potent receptor antagonist as evidenced by the inhibition of the binding of 125I-labeled PTA-OH to human platelets (IC50, 5.5 x 10(-9) M), inhibition of U-44069 induced aggregation of human platelet rich plasma (IC50, 1.1 x 10(-7) M), and competitive inhibition of contractions of the guinea pig tracheal chain induced by U-44069 (pA2,9.0). The compound was also active in vivo as shown by inhibition of arachidonic acid and U-44069 induced bronchoconstriction in the guinea pig (ED50 values, 0.04 and 0.03 mg/kg i.v., respectively), U44069 induced renal vasoconstriction in the pig (ED50, 0.02 mg/kg i.v.), and inhibition of ex vivo aggregation of rhesus monkey platelets to U-44069 (active 1-5 mg/kg p.o.). The selectivity of the compound was indicated by the failure to inhibit, first, ADP-induced human or primate platelet aggregation and, second, bronchoconstriction in the guinea pig in vivo and contraction of the guinea pig tracheal chain in vitro to a variety of agonists. It is concluded that L-670,596 is a potent, selective, orally active thromboxane A2/prostaglandin endoperoxide receptor antagonist.
Anesthesia↗
The use of synthetic thromboxane A2 (TXA2-S) and a new class of thromboxane antagonists, indole-2-propanoic acids to characterize the thromboxane receptor.
Explore the source record for details and available documents.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Tetrahydrocarbazol-1-acetic acids: new class of thromboxane receptor antagonists.
Explore the source record for details and available documents.
Acetates↗
The affinities of prostaglandin H2 and thromboxane A2 for their receptor are similar in washed human platelets.
Both thromboxane A2 (TXA2) and its precursor prostaglandin H2 (PGH2) are labile and share a common receptor. The affinities of these two compounds for their putative common receptor are unknown. We compared the potencies of TXA2 and PGH2 to aggregate human platelets and bind to the TXA2/PGH2 receptor. TXA2 was more potent than PGH2 in initiating aggregation in platelet-rich plasma, EC50 of 66 +/- 15 nM and 2.5 +/- 1.3 microM, respectively. In washed platelets, however, PGH2 was more potent than TXA2 with EC50 values of 45 +/- 2 nM and 163 +/- 21 nM, respectively. The affinity of these two compounds in washed platelets was determined in radioligand competition binding assays employing [125I]-PTA-OH. The Kd values for PGH2 and TXA2 were 43 nM and 125 nM, respectively. The results demonstrate that the affinity of PGH2 for the platelet TXA2/PGH2 receptor is greater than previously thought. The data raise the possibility that PGH2 may significantly contribute to the responses attributed to TXA2 in vivo.
Binding, Competitive↗