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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 325 records · Page 18Linked to original sources
PubMed1990

Hydrolysis of polyphosphoinositides in astrocytes by platelet-activating factor.

In primary astrocyte cultures, picomolar concentrations of platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF) evoked the formation of inositol phosphates (InsP), including inositol trisphosphate. This effect was not observed with the biologically inert lyso-PAF, nor in cells pretreated with phorbol myristate acetate to downregulate receptors. PAF at concentrations greater than or equal to 10(-9) M did not elevate InsP, suggesting some form of uncoupling of the receptor from phospholipase C. The responsiveness of astrocytes to PAF is further evidence for the role of these cells in the central nervous system response to trauma.

Animals↗
PubMed1990

Further characterisation of excitatory amino acid receptors coupled to phosphoinositide metabolism in astrocytes.

Excitatory amino acids stimulate phosphoinositide breakdown in astrocytes with the following rank order of effect: quisqualate greater than ibotenate = glutamate greater than kainate greater than N-methyl-D-aspartate. Quisqualate-induced responses were resistant to blockade with a range of receptor antagonists whereas those to glutamate were partially reversed by gamma-D-glutamylaminosulphonic acid and gamma-D-glutamylglycine. These antagonists were, however, more effective against kainate-stimulated phosphoinositide metabolism. These experiments together with those where combinations of agonists were used, suggest that the kainate-induced and, to some extent, the glutamate-induced responses were due to membrane depolarisation and that quisqualate activates a non-ionotropic class of receptor at which glutamate and ibotenate are partial agonists.

Astrocytes↗
PubMed1990

Serotonin inhibits ATP-induced mobilization of arachidonic acid but not phosphoinositide turnover in astrocytes.

In response to ATP, astrocytes accumulate inositol phosphates and release arachidonic acid (AA) from phospholipid stores, events which may be linked through intracellular calcium mobilization and activation of phospholipase A2. When cells were exposed to ATP in the presence of serotonin there was a dose-dependent inhibition of AA release, an effect which was reversed by methysergide. However, the accumulation of inositol phosphates due to ATP was elevated in the presence of serotonin, and this effect was again reversed by methysergide. The mechanism by which serotonin inhibits ATP-induced arachidonate mobilization does not, therefore, involve the purinergic receptor or its coupling to inositol phospholipid pools. The hydrolysis of polyphosphoinositides by serotonin and subsequent generation of inositol trisphosphate may deplete a specific intracellular calcium store normally available to ATP, the mobilization of which stimulates phospholipase A2 and thus AA release.

Adenosine Triphosphate↗
PubMed1990

Stimulation of thromboxane release from primary cell cultures derived from human astrocytic glioma biopsies.

Stimulation of primary cultures of rat astrocytes with appropriate agents results in the mobilization of arachidonic acid from intracellular lipid pools and the synthesis of eicosanoids. Thromboxane A2 is one of the major prostanoids released upon stimulation with calcium ionophore, phorbol esters, and ATP; but a number of other predicted effectors are inactive. In an attempt to understand the pathophysiological significance of eicosanoid release from astrocytes, primary cultures have been derived from human astrocytic glioma biopsies. The majority of cells in the cultures expressed glial fibrillary acidic protein (GFAP), frequently in conjunction with vimentin and fibronectin. Cell sorting revealed that a significant proportion of cells in the cultures from the high-grade (malignant) tumors expressed epidermal growth factor receptor, indicative of neoplastic cells. Both effective and ineffective agents in rat cultures were tested for their ability to stimulate release of thromboxane from these gliomas, and also from cultures of medulloblastoma and ependymoma which contained significant numbers of GFAP-positive cells. Only cells from the high-grade tumors released thromboxane in response to the known effective stimuli. While the muscarinic agonist carbachol was ineffective, norepinephrine evoked thromboxane release from malignant astrocytomas. These data show that cells derived from malignant human gliomas retain the ability to release thromboxane upon stimulation and suggest that a transformation in receptor coupling might accompany neoplasia, such that the cells now respond to a previously ineffective agonist.

Astrocytes↗
PubMed1990

Retrotracheal goiter: a diagnostic and therapeutic problem.

A patient with chronic cough and recent dysphagia was found to have a retrotracheal mass extending into the visceral mediastinum on chest roentgenogram. A computed tomographic scan confirmed a retrotracheal lesion, which was believed to be of lymphatic origin. A thyroid scan demonstrated downward displacement of the left lobe but little uptake in the mass. Histological findings of mediastinal biopsies were inconclusive. A large retrotracheal thyroid adenoma was easily excised through a right thoracotomy. The approach to diagnosis and, in cases of doubt, the safety of surgical access through thoracotomy for thyroid lesions in this unusual site is discussed.

Adenoma↗
PubMed1990

Measurement of psychiatric disorder in rheumatoid arthritis.

In a detailed physical and psychiatric assessment of 80 patients with definite or classical rheumatoid arthritis (RA) different instruments were used to measure psychiatric disorder. The prevalence of psychiatric disorder was 21% when assessed by the PSE/CATEGO programme and 24% according to RDC criteria, but these figures were nearly doubled if a lower threshold was used to define psychiatric disorder. This study demonstrates how symptoms directly attributable to arthritis may inflate the estimated prevalence of psychiatric disorder in RA and erroneously indicate a direct relationship between severity if RA and psychiatric disorder. In fact, the best prediction of psychiatric disorder resulted from using a combination of measures of social stress and severity of RA.

Activities of Daily Living↗
PubMed1990

The Benzodiazepine Withdrawal Symptom Questionnaire.

A self-report questionnaire is described which records the main symptoms experienced during withdrawal from benzodiazepines in pharmacologically dependent patients. The questionnaire consists of 20 items; evidence is given that these are reasonably independent and are sensitive in detecting withdrawal symptoms from a study of 68 patients undergoing slow withdrawal from benzodiazepines.

Anti-Anxiety Agents↗
PubMed1990

The Nottingham Study of Neurotic Disorder: relationship between personality status and symptoms.

Two hundred and ten psychiatric patients with one of three DSM-III diagnoses, generalized anxiety disorder (N = 71), panic disorder (N = 74) or dysthymic disorder (N = 65), were included in a clinical trial in which diazepam, dothiepin or placebo tablets, cognitive and behaviour therapy, or a self-help package were given over ten weeks. Personality status was assessed independently using a structured interview, the Personality Assessment Schedule. One hundred and ninety-eight patients had personality assessments, 89% with a close informant. Thirty-six per cent had a personality disorder and these patients had more severe psychopathology than those with no personality disorder. Personality disorder was more common in patients with dysthymic disorder and this group responded less well to treatment. The category of personality disorder had no apparent influence on symptoms.

Anxiety Disorders↗
PubMed1990

ATP-evoked arachidonic acid mobilization in astrocytes is via a P2Y-purinergic receptor.

To reveal more of the mechanism whereby ATP induces arachidonic acid (AA) mobilization in astrocytes, primary cell cultures prelabeled with [3H]AA were exposed to ATP and various analogs. Release of 3H was dose and time dependent and was inhibited by blocking ATP binding. The potencies of a range of ATP analogs in mobilizing AA were consistent with that predicted for the involvement of a P2Y-purinergic receptor. Mobilization of AA was not due to non-specific cell permeabilization, as assessed by leakage of cytoplasmic lactate dehydrogenase. AA mobilization by ATP was reduced when mobilization of intracellular calcium was inhibited and in the absence of extracellular calcium. Thapsigargin, which induces release of intracellular calcium, evoked mobilization of AA and thromboxane formation, findings similar to the effects of ATP. These results suggest that ATP stimulates AA mobilization via a P2Y-purinergic receptor and that, although extracellular calcium is involved, mobilization of intracellular calcium activates phospholipase A2.

Adenosine Triphosphate↗
PubMed1990

Evidence for an astrocyte-derived vasorelaxing factor with properties similar to nitric oxide.

To determine whether astrocytes release nonprostanoid vasodilators, cells on microcarrier beads were superfused with various agents in the presence of indomethacin, and the effluent was bioassayed and also analyzed for nitric oxide by a chemiluminescence technique. Bradykinin and A23187 induced release of a factor that relaxed arterial rings, an effect that was blocked by hemoglobin. The effluent contained either nitric oxide or a related compound that could be reduced to nitric oxide. Production of this factor was competitively inhibited by the arginine analogs NG-nitro-L-arginine and NG-methyl-L-arginine and could be restored with L-arginine. Quisqualate and norepinephrine were also effective in causing the release of nitric oxide from astroglial cells. Thus, astrocyte-derived relaxing factor has properties similar to those of an endothelium- and neuron-derived relaxing factor.

Animals↗
PubMed1990

Risk factors of female HIV-seropositive patients attending the clinic for sexually transmitted diseases at St Mary's Hospital, London.

Of 3450 women tested for antibodies to human immunodeficiency virus HIV-1 and HIV-2 between September 1985 and July 1989, 61 were positive (1.8%). Twenty-seven of these (44%) were presumed to have acquired their HIV infection by heterosexual contact and 23 (38%) were intravenous drug addicts. In geographical origin, 23 (38%) of the patients were from the UK and 19 (31%) from Africa. Amongst these 61 women, 2 (3%) have since died, one committed suicide and one was suspected of committing suicide.

Adolescent↗
PubMed1990

Should anticholinergics be used in acute severe asthma?

Anticholinergic drugs have been used in Western medicine for the treatment of asthma since the early 19th century. Studies evaluating drug efficacy in acute severe asthma over the last decade have renewed interest in the optimal use of anticholinergics in this condition. Unlike other bronchodilators (i.e., beta 2-agonists and methylxanthines), the anticholinergics produce bronchodilation only by inhibiting cholinergic-mediated bronchospasm. Therefore, anticholinergic drugs are more dependent on the mechanism of bronchospasm than other bronchodilators. The 18 clinical trials of anticholinergics in acute severe asthma are critically reviewed for design and endpoint measurements. Anticholinergics alone produce a modest bronchodilation in acute severe asthma but are not as consistently effective as beta 2-agonists. Anticholinergics consistently produce an added bronchodilation to aerosolized beta 2-agonists in single- and multiple-dose studies. This bronchodilation appears to be greater in the more severely obstructed patients. This bronchodilation is generally modest (10-20 percent), has not yet been shown to produce greater overall outcome, and has not been evaluated against high-dose frequent administration of aerosolized beta 2-agonists. Currently, only the quaternary amine derivatives are recommended for use in acute asthma. These agents should be reserved as second-line agents for acute severe asthma except possibly for those patients presenting with more severe obstruction (peak expiratory flow rate less than 35 percent of predicted).

Acute Disease↗
PubMed1990

Efficacy of combined antidepressant therapy in resistant neurotic disorder.

A 35-year-old woman with persistent affective and phobic symptoms responded dramatically to a combination of isocarboxazid and amitriptyline, and this improvement was maintained over the next three-and-a-half years. Isocarboxazid was replaced by placebo, using double-blind procedure. The change to placebo was accompanied by a marked increase in anxiety and depressive symptoms, which resolved when active isocarboxazid was reintroduced. It is suggested that combined antidepressant therapy still has a place in the treatment of resistant neurotic disorder.

Adult↗
PubMed1990

Magnetic resonance imaging of bone marrow: diagnostic value in diffuse hematologic disorders.

Magnetic resonance imaging (MRI) has value in characterizing normal and abnormal bone marrow because of its ability to distinguish fat from other tissues. Due to this advantage, hematologic disorders resulting in alterations of the normal cellular and fatty marrow distribution can be appreciated. In this article, the role of MRI in diffuse hematologic disorders is emphasized. At birth, almost all marrow is cellular, but by age 25, cellular marrow is restricted to the axial skeleton and proximal femoral and humeral metaphysis. The remainder is fatty, consisting of 80% fat, 15% water, and 5% protein. With increased need for hematopoiesis, reconversion from fatty to cellular marrow occurs in many diffuse disease states. Diffuse diseases that affect bone marrow production are divided into four categories representing conditions that affect the pluripotent hematopoietic stem cell. These include stem cell failure resulting in aplastic anemia, uncontrolled stem cell proliferation as exemplified by polycythemia vera, stem cell dysplasia such as sickle cell anemia, and malignant transformations or replacement. The MRI appearance of these disorders is discussed in this article. The use of spin-echo (SE) sequences is the most common approach to bone marrow imaging. With T1-weighted SE images, fatty marrow will appear bright and cellular marrow, with lower fat content, will exhibit a lower density signal. With T2-weighted SE pulse sequences, contrast between fatty marrow and cellular marrow decreases. Contrast between fatty and cellular marrow is enhanced with chemical shift imaging, including Dixon out-of-phase imaging, as emphasized in this article. MRI presents a more global view of the bone marrow than biopsy material and should provide a better understanding of diffuse hematologic disease progression and resolution.

Bone Marrow↗
PubMed1990

Platelet abnormalities in myeloproliferative disorders.

A large number of various platelet abnormalities are described in patients with MPD. These abnormalities serve diagnostic purposes only. They appear to have little or no predictive value regarding the clinical manifestations of the patients or the progress of the disease. Those platelet characteristics most consistently reported to be defective include a decrease in the platelet content of serotonin and adenine nucleotides, decreased platelet density, an abnormal ultrastructure characterized by paucity of granules and hypertrophy of the surface connecting canicular system, an altered membrane glycoprotein profile that includes reduced levels of GPIb, and reduced lipoxygenase activity and aggregation response with epinephrine. These abnormalities may originate at the megakaryocyte level. Furthermore, the released abnormal platelets may undergo modification of their functional and biochemical characteristics as a result of episodes of intravascular thrombosis or aging in circulation or as a result of the progression and treatment of the disease, thus creating the paradoxic and often conflicting relationship between the thrombotic and hemorrhagic events and the results of platelet functional tests as observed in this disorder.

Blood Platelets↗
PubMed1990

Safety of frequent high dose nebulized terbutaline in children with acute severe asthma.

Forty-four Pediatric Intensive Care Unit (PICU) admissions for acute severe asthma in 27 children between 8/80 and 10/86 were reviewed to determine the safety of prolonged administration of frequently nebulized terbutaline. The mean dose of nebulized terbutaline was 0.2 mg/kg/dose (range = 0.1 to 0.4 mg/kg/dose) given at a mean frequency of 2.4 +/- 1.2 hours. Seven patients received continuous nebulization at a dose of 0.4 +/- 0.2 mg/kg/h. All patients were placed on continuous cardiorespiratory monitoring. Emergency room therapy was determined by the primary emergency room physicians. Upon admission to the PICU, the mean +/- SD heart rate was 150 +/- 21 bpm and the respiratory rate was 44 +/- 16 bpm. After institution of therapy, these parameters decreased to a similar degree in parallel. The maximum decrease after 36 hours was 28% and 37% for heart rate and respiratory rate, respectively. No cardiac arrhythmias were noted. The initial PaCO2 upon admission to the PICU was 32 mm Hg (range = 24 to 44 mm Hg), the maximum decrease in PaCO2 generally occurred during the 6-hour to 12-hour time interval following admission. We conclude that frequent administration of high doses of nebulized terbutaline is safe in the management of acute severe childhood asthma even in the setting of prolonged administration to the hospitalized child.

Acute Disease↗