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Biomedical subjects

K O'Flynn

Publications and source records attributed to K O'Flynn.

At least 19 recordsLinked to original sources

Medical education in London during 1939-41, with special reference to the Blitz.

INTRODUCTION: This article is concerned with medical education in London during 1939-41. It is set against the London Blitz, an event that was then unique in its subjecting of civilians to an intense and prolonged aerial bombardment. Its very uniqueness ensured that medical students, like others in the capital, had no set rules of conduct with which to govern their response to death and destruction on such an unprecedented scale in an urban area. EVACUATION: For students at London's world-famous medical schools, the outbreak of war in 1939 resulted in the execution of evacuation plans formulated during the 1930s; these are outlined in the text. The London teaching hospitals and their attached medical schools were removed to sector hospitals and, in the case of the medical schools, to universities and colleges in areas deemed to be safe. MEDICAL TEACHING DURING THE WAR: Just as the schooling of children evacuated from Britain's big cities was subject to considerable disruption during this period, so was medical education. This article attempts to both chart the effects of these difficulties and study the manner in which the medical schools and, more particularly, London medical students, overcame them. Emphasis is placed on the dramatic months of the Blitz, not least because of the moulding effect such a sudden experience of warfare must have had on the very young, mainly male, students who lived through it. Finally, mention is made of some of the medical innovations the improvisations of the Blitz brought about.

Education, Medical↗

Comparison of the cellular molecular stress responses after treatments used in bladder cancer.

OBJECTIVE: To investigate the molecular stress responses related to the quality of recovery of normal tissue after various treatments for bladder cancer, i.e. hyperthermia, ionizing radiation, mitomycin-C and 5-aminolaevulinic acid photodynamic therapy (ALA-PDT). MATERIALS AND METHODS: The study focused particularly on intracellular fibroblast levels of heat-shock protein-47 (HSP47) and HSP72, which are associated with collagen metabolism and the development of tolerance to repeated treatment, respectively. Iso-effective treatment doses (50% clonogenic cell survival) of each method were delivered to a 3T6 murine fibroblast model. Intracellular extracts were analysed at 3, 6, 9, 12 and 24 h after treatment, using Western blot analysis to compare the levels of HSP47 and HSP72. Time-matched treatment and control groups were quantified by comparison with actin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression using appropriate software. RESULTS: There were various changes in levels of HSP expression with treatment method; HSP47 levels were significantly higher after hyperthermia and radiation but not with mitomycin-C or ALA-PDT. HSP72 levels were significantly higher with all methods except ALA-PDT. CONCLUSIONS: Hyperthermia and ionizing radiation are associated with early increases in levels of HSP47 (a marker of collagen metabolism), in contrast to ALA-PDT and mitomycin-C. These findings are compatible with clinical findings where fibrosis/scarring is common with the first two but not the last two methods. In addition, all methods except ALA-PDT are associated with an increase in HSP 72 (a protein associated with cellular tolerance) and this may help to explain, at a cellular level, why resistance to repeated ALA-PDT treatments does not seem to occur.

Animals↗

The growth hormone response to baclofen in obsessive compulsive disorder: does the GABA-B receptor mediate obsessive anxiety?

The growth hormone (GH) response to the gamma amino butyric acid type B (GABA-B) receptor agonist baclofen was measured in 10 Caucasian out-patients with DSM-III-R obsessive compulsive disorder (OCD) and 10 healthy comparison subjects. The patients also underwent a dexamethasone suppression test. The GH response was similar in both groups and there was a low rate of dexamethasone non-suppression in the patients. The data do not suggest that GABA-B receptor dysfunction is a feature of obsessive anxiety.

Adult↗

Secondary oxalosis and sperm granuloma of the epididymis.

A 30 year old man with a 20 year history of chronic renal failure who presented with a testicular lesion is described. The lesional pathology, secondary oxalosis, and associated sperm granuloma of the epididymis was clinically considered to be an intrascrotal tumour. The oxalate crystal deposition was present within the rete testis, the ductuli efferents, and the epididymis along with sperm granulomata. This seems to be a rare complication of secondary oxalosis associated with chronic renal failure and having both clinical and pathological implications.

Adult↗

Baclofen-induced growth hormone release in major depression: relationship to dexamethasone suppression test result.

Fifteen patients with DSM-III-R major depression and 15 matched comparison subjects underwent baclofen-induced growth hormone (GH) release and the dexamethasone suppression test (DST). The GH responses of the patients were significantly blunted, especially those of the patients who were DST nonsuppressors. These findings may indicate lower than normal responsivity of type B gamma-aminobutyric acid (GABA-B) receptors in depression and a relationship between GABA-B receptor abnormality and dysfunction of the hypothalamic-pituitary-adrenal axis.

Adult↗

Pyridostigmine-induced growth hormone responses in healthy and depressed subjects: evidence for cholinergic supersensitivity in depression.

Theorists have extrapolated the cholinergic supersensitivity theory of affective disorder from a convincing and broad spectrum of clinical observation and research. This hypothesis is tested using a neuroendocrine probe approach with the challenge drug pyridostigmine, an indirect cholinergic agent thought to release growth hormone (GH) by decreasing inhibitory somatostatin tone. The consequent increments in plasma GH were considered to reflect central acetylcholine responsivity. Fifty-four volunteers were tested: 27 DSM-III-R major depressives (18 women and 9 men) and 27 age- and sex-matched healthy controls. Subjects were cannulated at 9.00 h following an overnight fast and two baseline samples were taken at 15 min intervals. Pyridostigmine 120 mg was administered orally and thereafter samples were taken at the time points +60, +90, +120 and +180 min. GH responses were significantly greater in depressives than controls and this effect was more marked for men than women. These results support the proposal that muscarinic upregulation and/or supersensitivity is associated with depression.

Acetylcholine↗

Effect of fluoxetine on noradrenergic mediated growth hormone release: a double blind, placebo-controlled study.

Twelve patients with DSM-III-R major depressive illness were tested for growth hormone (GH) response to desipramine (DMI), a noradrenergic (NA) reuptake inhibitor. The response is mediated by NA alpha 2 receptors. They were then randomly assigned to treatment under double-blind conditions with either fluoxetine, the highly selective serotonin reuptake inhibitor or placebo. After 4 weeks they were retested. Fluoxetine but not placebo was effective in promoting recovery in four of the six patients treated. Patients treated with fluoxetine showed a significant decrease in DMI-mediated GH release irrespective of therapeutic outcome. This is consistent with marked alteration of NA function and raises questions as to the selectivity of fluoxetine.

Adult↗

Gender and age differences in the growth hormone response to pyridostigmine.

Thirty healthy subjects 12 males and 18 females were given the acetylcholinesterase inhibitor pyridostigmine (120 mg) orally. The growth hormone (GH) response was measured as the maximum GH level post-pyridostigmine relative to baseline. Twenty-six subjects increased their GH level in response to pyridostigmine. Responses in females were considerably greater than those in males and correlated closely with serum oestradiol levels. Overall there was a significant negative correlation between GH response and age.

Adult↗

Endoballoon rupture and stenting for pelviureteric junction obstruction: technique and early results.

Endoballoon rupture and stenting was performed on 31 patients with pelviureteric junction obstruction. A percutaneous antegrade approach was used in 20 patients, a retrograde technique in 11. Clinical and renographic improvement was seen in 21 patients. Four patients later underwent nephrectomy, all of whom had a GFR of less than 20% in the affected kidney. Endoballoon rupture is technically undemanding, easier and less invasive than endopyelotomy. In patients with adequate renal function it provides a suitable alternative to pyeloplasty.

Adolescent↗

Binding of monoclonal antibody to CD16 causes calcium mobilization in large granular lymphocytes but inhibits NK killing.

A monoclonal antibody (mAb), CLB/FcR gran I, reactive with the CD16 Fc receptor (FcRlo/FcRIII) of human cells, leads to calcium mobilization in large granular lymphocytes (LGL) but not in granulocytes. Identical responses are obtained with F(ab')2 fragments of this antibody, indicating that the response is independent of Fc-FcR binding, and that bivalent cross-linking of this receptor is adequate for optimal calcium mobilization. The calcium response was greater in CD3- LGL compared to CD3+ LGL, although the response was augmented in the latter cells by prior rosetting with sheep red blood cells (SRBC). Calcium mobilization in CD3- LGL induced by CLB/FcR gran I is associated with inhibition of natural killer cell (NK) killing, and inhibition of the enhanced NK killing induced by the anti-CD2 low-density monoclonal antibody, 9.1. This supports the view that the NK-enhancing activity of 9.1 is due to simultaneous binding to CD2 and CD16, and may in fact be transduced through the CD16 molecule. The variable reported effects of anti-CD16 antibodies on NK killing are likely to reflect the epitope bound rather than the isotype of antibody used, since F(ab')2 fragments of CLB/FcR gran I also inhibit NK killing.

Antibodies, Monoclonal↗

Mechanism of human monocyte activation via the 40-kDa Fc receptor for IgG.

It is shown that a mAb specific for the human 40-kDa FcR (FcRII) leads to activation of human monocytic cells but that extensive cross-linking of the receptor is required. Calcium mobilization can be induced in immature monocytic cells (undifferentiated U937 cells) and peripheral blood monocytes with an intact IgG1 anti-FcRII antibody (CIKM5) but not by F(ab')2 fragments of this antibody. The intact antibody can bind in a tripartite manner by its two F(ab') sites and its Fc-binding site whereas the F(ab')2 fragments of this antibody can only bind in a divalent fashion. A rise in intracellular free calcium ion concentration occurs when F(ab')2 fragments are cross-linked with F(ab')2 anti-mouse Ig indicating that more extensive cross-linking of FcRII is required rather than an obligatory requirement for an Fc-FcRII interaction. Calcium mobilization in response to intact or cross-linked F(ab')2 fragments of CIKM5 is associated with superoxide production only in IFN-gamma-primed peripheral blood monocytes and IFN-gamma differentiated U937 cells indicating that the activation signal produced via FcRII is inadequate to fully stimulate non-"primed" cells. A second mAb reactive with FcRII (2E1) does not cause calcium mobilization in monocytes or U937 cells, and partially blocks the effects of CIKM5. 2E1 also blocks CIKM5 superoxide production in IFN-gamma-primed monocytes and differentiated U937 cells. This may be explained in part by the fact that 2E1 is an IgG2a antibody and can only participate in bipartite binding with FcRII. When 2E1 is cross-linked with F(ab')2 anti-mouse Ig there is a small calcium response. This does not cause superoxide generation in IFN-primed monocytes but does do so in IFN-gamma differentiated U937 cells. FcRII is also expressed on granulocytes and some B cells but the effects of cross-linking the receptor on these cells differ from those seen in monocytes.

Antibodies, Monoclonal↗

Interactions between prostacyclin analogue ZK 36374 and heparin in their effects upon platelet function.

Prostacyclin and heparin can be administered to patients concurrently, with the aim of maximizing anticoagulant effect. It has been suggested that the two agents may interact in their effects upon platelet function. We have therefore studied this parameter in the presence of ZK 36374, a chemically stable analogue of prostacyclin and heparin, alone and in combination. Platelet responses to ADP and thrombin have been studied by standard aggregometry, and intra-platelet calcium mobilization has simultaneously been recorded after loading the cells with the fluorescent calcium indicator, Quin 2. ZK 36374 alone consistently inhibited platelet aggregation and calcium mobilization in response to ADP and thrombin, in a dose-dependent fashion. Heparin alone did not significantly alter the responses to ADP but consistently reduced those to thrombin. Pre-mixture of ZK36374, with heparin, was shown to interfere with the ability of the prostacyclin analogue to inhibit platelet aggregation and calcium flux in response to ADP. In contrast, ZK 36374 inhibition of platelet responses was markedly enhanced when thrombin was the agonist.

Adenosine Diphosphate↗

The relationship between mitogen-induced membrane potential changes and intracellular free calcium in human T-lymphocytes.

We have investigated the effects of mitogenic lectins on human T-lymphocytes, isolated from peripheral blood, and cells from the T-cell clone, HPB-ALL, using the fluorescent dyes, bis-thiobarbiturate tri-methineoxonol (bisoxonol) and quin2 to sense changes in membrane potential and intracellular free [Ca2+], respectively. The resting potential of both cell types is close to the K+ equilibrium potential. Changes from the resting level occur when mitogenic concentrations of either concanavalin A or phytohaemagglutinin are added. T-lymphocytes undergo a decrease in emission, maximal at 1 to 2 min, corresponding to a small membrane hyperpolarization. This is followed by a depolarization to approximately the resting level. HPB-ALL cells, on the other hand, respond to the mitogens by a sustained increase in fluorescence, denoting a depolarization, that is maximal at 4 to 5 min and 7 to 9 min, respectively. The Ca2+-dependence of these phenomena indicates that the membrane potential response, in both cell types, is the resultant of two opposing effects: a Ca2+-sensitive ion movement tending to hyperpolarize the cells and a Ca2+-insensitive effect that generates a depolarization. Our results suggest that Ca2+-activated K+ channels are responsible for the first effect and that an inward Na+ movement accounts for the depolarization signal in T-lymphocytes. In HPB-ALL cells only part of the depolarization is Na+-dependent. Although the effects elicited by phytohaemagglutinin occur more slowly than those produced by concanavalin A, similar membrane potential and [Ca2+]i changes occur.

Aminoquinolines↗

CD2 and CD3 antigens mobilize Ca2+ independently.

Antigen-induced stimulation of T cells is mediated via the CD3 antigen receptor (Ti) complex and monoclonal antibodies (mAb) reacting with CD3 and Ti result in rapid intracellular Ca2+ mobilization, followed by monocyte-dependent proliferation. Combinations of mAb to CD2, the sheep red blood cell receptor, also mobilize calcium and induce mitogenesis and purified phytohemagglutinin (PHA) stimulates T cells predominantly by interaction with this molecule. It has been suggested that activation via CD2 requires the presence of CD3 and that the hydrophobic epsilon chain of CD3 is the T cell calcium channel. To investigate this further we have obtained large numbers of natural killer (NK) cells which express CD2 but not CD3 from a patient with a chronic expansion of this lymphocyte subpopulation. It is shown that calcium mobilization can be induced in these cells by mAb to CD2 and purified PHA but not by anti-CD3 mAb. This indicates that calcium mobilization can be induced via the CD2 molecule in NK cells not expressing CD3 and that activation through CD2 is separate from the antigen receptor CD3 pathway.

Aminoquinolines↗