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Biomedical subjects

A J MacDonald

Publications and source records attributed to A J MacDonald.

33 records · Page 2Linked to original sources
PubMed1986

Enteral and systemic release of leukotrienes during anaphylaxis of Nippostrongylus brasiliensis-primed rats.

Rats with acquired immunity to the intestinal nematode Nippostrongylus brasiliensis develop anaphylaxis after i.v. challenge with an extract of worm antigen, with the small intestine being the primary shock organ. In the present study we have shown that these events were associated with significant elevations in intestinal and plasma concentrations of leukotrienes LTB4 and LTC4. The changes were observed in immune rats over 10-, 30-, and 60-min intervals after antigen challenge but were absent in control animals. These lipid mediators were identified both in the perfusate of the gut lumen, which contained large quantities of mucus, and in homogenates of intestinal tissue. In addition, significant elevations in the concentrations of plasma LTB4 and LTC4 were detected in immune challenged rats but not in controls. Leukotrienes were identified by radioimmunoassay and validated by reverse-phase high-performance liquid chromatography (RP-HPLC). RP-HPLC analysis of SRS-A leukotrienes in immune challenged rats indicated that LTC4 was the predominant sulfidopeptide leukotriene at 10 min, with almost complete biodegradation to LTD4 and LTE4 within 30 min. Infected rats also had significant increases in the numbers of intestinal mucosal mast cells (MMC) and eosinophils. Evidence of MMC activation during anaphylaxis was obtained by showing significant elevations of intestinal and systemic concentrations of their exclusive serine enzyme, rat mast cell proteinase II (RMCPII). Thus, the release of substantial amounts of leukotrienes in the gut and plasma of N. brasiliensis-primed rats after interaction with worm antigens suggests that these potent mediators may play an important role in allergic-type hypersensitivity known to occur during immune reactions against parasitic helminths.

Anaphylaxis↗
PubMed1986

Do general practitioners "miss" depression in elderly patients?

In a study of the prevalence of depression in 235 elderly patients who attended general practice surgeries less than 12% of the disagreement between the research assessment of depression and the general practitioner's assessment was due to "missed" depression. There were, however, low rates of referral and of treatment with antidepressant drugs. If these findings are confirmed the study of the management and outcome of depression in such patients may be more rewarding than attempts to improve the recognition of depression.

Adult↗
PubMed1986

Enhancement of leukocyte cytotoxicity after exercise-induced asthma.

We have previously shown that there were elevations of neutrophil chemotactic activity (NCA) and increases in the percentages of neutrophil and monocyte complement rosettes after exercise-induced asthma (EIA). These observations suggested that leukocyte activation may occur after EIA, possibly as a result of the release of mast-cell-associated mediators. In the present study, we have attempted to establish whether neutrophils and monocytes are functionally altered after EIA as assessed by changes in their cytotoxic capacity. Cytotoxicity was assessed by a direct visual killing assay using opsonized (complement-coated) schistosomula of Schistosoma mansoni as target organisms. Neutrophils and mononuclear cells obtained from 8 patients after exercise-induced asthma (EIA+ve) had increased cytotoxicity for opsonized schistosomula for as long as 60 min after exercise. These changes were preceded by elevations in the concentrations of serum high molecular weight NCA (which were maximal at 10 min after exercise). In asthmatic patients who did not develop exercise-induced asthma (EIA-ve), no significant increases in neutrophil or mononuclear cell killing of schistosomula, or serum NCA concentrations, were observed. There was a highly significant correlation (p less than 0.001) between the reduction in FEV1 and the increases in neutrophil cytotoxicity. In 5 EIA+ve patients, administration of disodium cromoglycate (cromolyn) prior to the exercise task inhibited both the enhancement in neutrophil and mononuclear cell cytotoxicity, as well as the elevations in circulating NCA and the reductions in FEV1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1986

Enhanced granulocyte cytotoxicity by mediators derived from anti-IgE-stimulated human leucocytes.

Basophil-containing leucocyte fractions stimulated with an anti-human IgE, F(ab')2, generated histamine and the leukotrienes LTB4 and LTC4 with significant correlations between LTB4 and histamine (P less than 0.01; n = 26) and LTC4 and histamine release (P less than 0.001; n = 29) in the cell-free supernatants (SN). SN from these anti-IgE-treated cells enhanced the cytotoxicity of eosinophils and neutrophils (against complement-coated schistosomula of Schistosoma mansoni) in vitro. When SN were fractionated by reverse phase-high performance liquid chromatography (RP-HPLC), the enhancing activity for neutrophils was almost totally confined to fractions having LTB4 immunoreactivity (co-eluting as a single peak with the synthetic LTB4 marker). In contrast, the LTB4-containing fraction had minimal effects on eosinophil cytotoxicity, whereas synthetic histamine gave comparable enhancement to the unfractionated SN. The generation of LTs (but not histamine), as well as enhanced neutrophil cytotoxicity from basophil-containing leucocytes by anti-IgE treatment, was maximally inhibited by the 5-lipoxygenase inhibitors U-60, 257 and BW755C. Conversely, the cyclooxygenase inhibitor indomethacin did not significantly affect LT release, nor did it affect the subsequent cytotoxicity enhancing activity of SN from such cells. These results indicate that LTB4 and LTC4 are released from basophils, together with histamine, by IgE-dependent mechanisms, LTB4 enhances the cytotoxicity of bystander neutrophils, and histamine (and to a lesser extent, LTB4) augments eosinophil cytotoxicity.

Basophils↗
PubMed1985

Enhancement of human eosinophil- and neutrophil-mediated killing of schistosomula of Schistosoma mansoni by reversed type (IgE-mediated) anaphylaxis, in vitro.

Using human peripheral blood leucocytes we have developed a model for studying the effect of in vitro anaphylaxis on granulocyte-mediated killing of helminthic larvae (schistosomula (Sch) of Schistosoma mansoni). Leucocytes were incubated with either an F(ab')2 rabbit anti-human IgE (alpha E) or a control F(ab')2 prepared from non-specific rabbit IgG (alpha Ec). A time-dependent enhancement of eosinophil- and neutrophil-mediated complement (C) or antibody- (Ab) dependent killing of Sch was observed following incubation with alpha E, but not alpha Ec. Optimal enhancement of granulocyte killing was dependent on the concentration of alpha E, pre-incubation of granulocytes with alpha E prior to addition to C coated Sch, as well as the granulocyte: Sch ratio. Baseline killing of Ab and/or C coated Sch by eosinophil rich cells was significantly greater than neutrophil rich suspensions and both were proportionally increased following incubation with alpha E. Enhanced eosinophil and neutrophil killing by alpha E required the presence of mononuclear cells containing basophils, whereas there was no difference in the killing of C or Ab coated Sch when eosinophils or neutrophils alone were incubated with alpha E or alpha Ec. This IgE and leucocyte-dependent model might facilitate the isolation and identification of the pharmacological mediator(s) of hypersensitivity which enhance eosinophil or neutrophil killing of appropriately opsonized helminthic larvae.

Anaphylaxis↗
PubMed1983

Use of cupric oxide needles in the prophylaxis of induced copper deficiency in lambs grazing improved hill pastures.

Cuprix oxide needles as a single oral dose were administered to ewes in the prepartum period, and to one member of each pair of twin lambs at between three and five weeks of age when grazing hill pastures improved by liming and reseeding. Lambs derived from dosed or undosed ewes and treated at three to five weeks of age were maintained in normocupraemia and showed no signs of ill-thrift. Lambs derived from dosed or undosed ewes but not themselves dosed showed hypocupraemia and ill-thrift. The lambs derived from the dosed ewes took longer to become hypocupraemic, but showed only a transient benefit from the ewe treatment. The dosed ewes showed a delay in the onset of hypocupraemia compared with the undosed ewes but there were no definable differences in performance between the two groups.

Administration, Oral↗
PubMed1981

Symptom relief and the placebo effect in the trial of an anti-peptic drug.

In order to determine some of the factors involved in the response of duodenal ulcers to placebo treatment, the following factors were studied prospectively during a double-blind, placebo-controlled trial: demographic data; duration of illness and effect of treatment; expectation of success or failure of the new drug; presence of psychiatric problems; and suggestibility. Healing (measured by endoscopy) occurred in 37 patients, 17 of whom were receiving placebo; relief of symptoms occurred in 35 patients, 16 of whom were receiving placebo. There was no significant difference between drug and placebo. Healing was significantly associated with relief of symptoms but with no other variable. Relief of symptoms was more common in male patients and in those from higher social classes, as well as in patients who expected a complete cure and those without evidence of psychiatric problems. the natural history of the disease may be different in these patients. Unexpectedly, suggestibility was not associated with healing or relief of symptoms in the patients receiving placebo.

Adult↗
PubMed1980

Non-organic gastrointestinal illness: a medical and psychiatric study.

One hundred consecutive referrals to a general medical out-patient clinic were evaluated psychiatrically under blind conditions in order to investigate the nature and occurrence of non-organic disease presenting as gastrointestinal illness. Twenty-eight patients had marked psychiatric illness with or without physical illness, and there was an association between psychiatric illness and the absence of organic disease, as determined by outcome at follow-up of 4-11 months. Patients with obsessional traits were more at risk of non-organic illness. Historical items indicating a likelihood of non-organic gastrointestinal illness included "nerves", "depression", unhappy childhood, early parental loss and early separations from parents during childhood. Psychiatric illness often persisted after treatment for physical symptoms. Some of the techniques used in this study to identify psychiatric illness could be usefully employed in everyday practice.

Adult↗
PubMed1977

Pharmacokinetic aspects of protriptyline plasma levels.

Plasma levels of protriptyline have been determined in 30 patients undergoing antidepressant therapy. After 3 1/2 weeks treatment at dosage levels of 40 mg/day, protriptyline plasma levels ranged from 430 to 1430 nmol/l. During this period only two-thirds of the subjects had definitely achieved asymptotic concentrations. Single dose studies in 5 volunteers suggest that the volume of distribution of protriptyline shows little intersubject variation. The half life of the drug, however, may vary appreciably from subject to subject, ranging from 54 to 198 h. The effects of two sedatives on mean protriptyline plasma levels have been determined. Mean plasma levels for nitrazepam recipients are indistinguishable from those for patients receiving no night sedation. The mean plasma levels for a group of patients receiving sodium amylobarbitone were significantly reduced. The problems of choice and early adjustment of dosages in order to achieve satisfactory plasma levels is discussed. For practical purposes it is suggested that early values may be of predictive significance in allowing early dosage adjustments to be made.

Administration, Oral↗
PubMedDate not supplied

Review: children and companion animals.

The literature concerning the relationship between the child and companion animal is reviewed including the possible use of companion animals as aids in the psychotherapy of children. The literature pertaining to cruelty to animals is also discussed. It is concluded that the evidence available is sufficient to justify further research into interactions between children and companion animals both in therapy and in the population generally, and some possible approaches are suggested.

Adolescent↗