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Biomedical subjects

S Murphy

Publications and source records attributed to S Murphy.

At least 37 records · Page 2Linked to original sources

Endogenous sex hormones and bone mineral density among community-based postmenopausal women.

In order to describe the relationships between endogenous sex hormones and bone mineral density in healthy postmenopausal women, we carried out a cross-sectional study of 90 community-based women, all at least one year since their last menstrual period (mean 9.6 +/- 4.9 years, range 1-22) and with a serum oestradiol level less than 100 pmol/l. None was currently using hormone replacement therapy. Serum oestradiol, testosterone, sex hormone binding globulin, dehydroepiandrosterone sulphate, and androstenedione were measured using standard techniques. Free oestradiol and testosterone indices were derived as the ratio of total hormone to sex hormone binding globulin, respectively. Total body, spine and hip bone mineral density (g/cm2) were measured by dual energy X-ray absorptiometry. Significant positive correlations were found between the free oestradiol and testosterone indices and bone mineral density at all sites. These relationships remained significant for the free oestradiol index after adjustment for age and body mass index. By stepwise multiple regression analysis, the free oestradiol index was an independent predictor of total body, spine and hip bone mineral density, accounting for 4-17% of the variance. These findings suggest an independent positive relationship between endogenous free oestradiol and total body, spine and hip bone mass even in the late postmenopause.

Aged

Polycythemia vera and myelofibrosis: correlation of MR imaging, clinical, and laboratory findings.

Magnetic resonance (MR) imaging was performed in 14 patients with biopsy-proved polycythemia vera (n = 4) or myelofibrosis (n = 10) to determine whether MR imaging findings can be correlated with the clinicopathologic diagnosis and established clinical parameters of severity (serum lactate dehydrogenase [LDH] and cholesterol levels) and chronicity (spleen size). Evaluation of marrow in the proximal femurs showed that patients could be categorized into three distinct groups based on anatomic patterns of normal fatty and abnormal low-signal-intensity (non-fatty) marrow in the femoral capital epiphysis (FCE) and greater trochanter (GT). Patients with nonfatty marrow in both the FCE and GT (n = 8) had significantly higher serum LDH (P less than .02) and lower serum cholesterol (P less than .02) levels than patients with fatty marrow in at least the GT (n = 6). Splenic volume, as measured from MR images, was significantly greater in the myelofibrosis group than in the polycythemia vera group (P less than .001). MR imaging provided a better understanding of these hematologic disorders and novel parameters for classification that are different from conventional histologic and laboratory data.

Adult

Beta-adrenergic agonists for acute, severe asthma.

OBJECTIVE: To critically review the use of beta-adrenergic agonists in acute, severe asthma with particular focus on aerosol administration. DATA SOURCES: English language articles published since 1971 on the use of beta-agonists for acute asthma. Studies were identified from bibliographies of book chapters, review articles, and other research articles. STUDY SELECTION: All studies (21 total) comparing systemic with inhaled beta-agonists were reviewed, regardless of their design or outcome. Selected studies highlighting specific aspects of beta-agonist use in acute asthma such as beta-agonists versus other bronchodilators, aerosol delivery, and intravenous beta-agonists were also reviewed. DATA EXTRACTION: Performed subjectively by the authors with specific aspects of quality discussed within the body of the article. DATA SYNTHESIS: The beta-agonists provide superior bronchodilation in acute severe asthma compared with either the methylxanthines and/or anticholinergics. The majority of studies found aerosolized beta-agonists to be either as effective as or more effective than parenteral beta-agonists and to produce fewer adverse cardiovascular effects. Studies showing preference for parenteral therapy have either been of poor design or used low doses of an aerosolized beta-agonist. Based on studies of aerosol delivery, there is no advantage of jet nebulization over metered-dose inhalers; however, other aspects, including ease of administration, favor nebulization as the delivery method of choice. The articles recommending intravenous beta-agonists consist of a series of uncontrolled cases. CONCLUSIONS: Aerosolized selective beta 2-agonists are the bronchodilator treatments of choice for acute, severe asthma. Attention to the details of dosing and delivery are required for optimal results. The final dose and dosing interval are determined by the patient's response. Intravenous beta-agonists are hazardous and cannot be recommended.

Administration, Inhalation

Campylobacter jejuni enteritis mistaken for ulcerative colitis.

Campylobacter jejuni is the most common bacterial cause of gastroenteritis and is often missed by routine stool cultures. Patients may present with a clinical syndrome and endoscopic findings that are similar to acute ulcerative colitis. Ciprofloxacin is currently the recommended antibiotic therapy.

Adult

Delivery of aerosolized medication to intubated babies.

We studied the delivery of aerosolized cromolyn sodium to intubated babies, and evaluated the effect of changes in delivery techniques. In addition, we compared these results with an in vitro model of aerosol delivery. Cromolyn sodium was used as a marker because once the drug is absorbed, it is excreted unchanged, approximately 50% in urine and 50% in bile. We demonstrated that, in vitro, a conventional, jet-type nebulizer aerosolized 20.5% of a test dose of cromolyn, and only 5.5% of the dose was recovered after passage through 60 cm of ventilator tubing and an endotracheal tube adapter. This increased to 44.5% nebulized and 19% recovered when the volume nebulized was increased from 2 mL to 5 mL. A submicronic nebulizer aerosolized 40% and delivered 33.5% of the test dose. A 20 mg dose of nebulized cromolyn sodium was used as a test dose in infants, after which urine was collected for 4 hours. Forty-three urine samples were collected, after the delivery of cromolyn test doses, from nine babies (16-128 days old) intubated for bronchopulmonary dysplasia. Both the jet and submicronic nebulizers were tested in two positions: 1) in place of the ventilator humidifier, and 2) at the endotracheal tube adapter. There were no statistically significant differences in cromolyn delivery for any system configuration. In all situations, means of less than 0.1% of the test dose were recovered in the urine. We estimated that in all cases, less than 1% of the test dose (approximately 50-100 micrograms of cromolyn) had been deposited in the lung. These results show that although the submicronic nebulizer aerosolized cromolyn more efficiently, no additional cromolyn could be detected in infants. We speculate that a significant portion of the smaller particles are exhaled.

Administration, Inhalation

Cerebrovascular changes in a rat model of moderate closed-head injury.

We have developed and tested a rat (Wistar) model of moderate concussion. Concussion is produced by controlled and repeatable mechanical fixed, closed-head injury. Moderate concussion in this model is characterized by 4 to 10 minutes of unconsciousness, absence of skull fractures or brain contusions, and few, if any, acute neurologic symptoms. By 2 hours postinjury, the subsequent trauma is further characterized by regional and global increases in cerebrovascular permeability and decreases in cerebral blood flow. Such changes are accompanied by brain swelling and two phases of elevated intracranial pressure; one lasting about 5 hours with a peak of about 10 mmHg, the other lasting more than 3 days postinjury with a peak of about 30 mmHg. Regional neurohistologic damage detected between 3 and 4 days postinjury correlates for the most part with earlier changes in regional permeability and blood flow. Significant morphologic changes which are characterized by patchy neuronal degeneration can be found in numerous forebrain locations, particularly in the frontal (coup) and entorhinal (contre coup) cortices. These observations have important parallels in human head trauma and suggest that this reliable physiological model may be a useful, relatively simple and inexpensive tool for investigating the mechanisms and therapeutics of head trauma.

Animals

Astrocytes, not neurons, produce docosahexaenoic acid (22:6 omega-3) and arachidonic acid (20:4 omega-6).

Elongated, highly polyunsaturated derivatives of linoleic acid (18:2 omega-6) and linolenic acid (18:3 omega-3) accumulate in brain, but their sites of synthesis are not fully characterized. To investigate whether neurons themselves are capable of essential fatty acid elongation and desaturation or are dependent upon the support of other brain cells, primary cultures of rat neurons and astrocytes were incubated with [1-14C] 18:2 omega-6, [1-14C]20:4 omega-6, [1-14C]18:3 omega-3, or [1-14C]20:5 omega-3 and their elongation/desaturation products determined. Neuronal cultures were routinely incapable of producing significant amounts of delta 4-desaturase products. They desaturated fatty acids very poorly at every step of the pathway, producing primarily elongation products of the 18- and 20-carbon precursors. In contrast, astrocytes actively elongated and desaturated the 18- and 20-carbon precursors. The major metabolite of 18:2 omega-6 was 20:4 omega-6, whereas the primary products from 18:3 omega-3 were 20:5 omega-3, 22:5 omega-3, and 22:6 omega-3. The majority of the long-chain fatty acids formed by astrocyte cultures, particularly 20:4 omega-6 and 22:6 omega-3, was released into the extracellular fluid. Although incapable of producing 20:4 omega-6 and 22:6 omega-3 from precursor fatty acids, neuronal cultures readily took up these fatty acids from the medium. These findings suggest that astrocytes play an important supportive role in the brain by elongating and desaturating omega-6 and omega-3 essential fatty acid precursors to 20:4 omega-6 and 22:6 omega-3, then releasing the long-chain polyunsaturated fatty acids for uptake by neurons.

Animals

Management of acute asthma.

The principal goal of treatment of the acute exacerbation of asthma is the rapid reversal of the airway obstruction which is best accomplished by the frequent administration of inhaled beta 2-agonists. In addition, the early addition of systemic corticosteroids improves the response in patients who incompletely respond to beta 2-agonists. If present, hypoxemia should be corrected with administration of supplemental oxygen. Close monitoring of the patient's response to treatment is essential and if the patient is over 4 years of age and can cooperate, this should include peak expiratory flow rate (PEFR) measurement.

Acute Disease

Co-localization of calcitonin gene-related peptide- and substance P-like immunoreactivity in mucosal intra-epithelial nerves in the toad colon.

Mucosal intra-epithelial nerve terminals have been found in the colon of the toad, Bufo marinus. Co-localized in the fibres are calcitonin gene-related peptide (CGRP)-like immunoreactivity (LI) and substance P (SP)-LI. The intraepithelial nerves are likely to be terminals of primary afferent sensory neurones. Fibres with vasoactive intestinal peptide (VIP)-LI or neuropeptide Y (NPY)-LI also supply the mucosa but do not penetrate the epithelium.

Afferent Pathways

TLC? Forget it.

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Consumer Behavior

Cerebral blood flow after treatment with ORG-2766, a potent analog of ACTH 4--9.

Regional cerebral blood flows (rCBF) were measured in conscious, male rats at 10, 30, 60 min and 24 hr after intravenous administration of a potent, behaviorally active analog of ACTH/MSH 4--9 (ORG-2766). Flows in the basal ganglia, hippocampus, septal area and frontal cortex were depressed significantly throughout the 60 min postinjection period. HYpothalamic and parietal flows were depressed at 10 and 30 min, but recovered by 60 min, whereas flow to the cerebellum was depressed between 30 and 60 min postinjection. The least changed and therefore relatively better perfused area throughout the first 60 min period was the occipital cortex. By contrast, at 24 hr, when perfusion of all brain regions had returned to near control levels, flow to the occipital cortex was elevated. During the first hour after treatment with either ORG-2766 or alphaMSH the patterns of regional circulation in the brain were qualitatively the same. The data suggest that ORG-2766 and, probably, alpha MSH trigger serially linked neurophysiologic changes in the brain lasting at least 24 hr, which organize the behavioral actions of this class of peptides on memory and attentional processes.

Adrenocorticotropic Hormone

Polycythemia vera. Increased expression of normal committed granulocytic stem cells in vitro after exposure of marrow to tritiated thymidine.

In previous studies of two patients with polycythemia vera (PV) and heterozygous at the X-linked locus for glucose-6-phosphate dehydrogenase (G-6-PD), only type A isoenzyme was found in non-lymphoid hematopoietic cells. However, some granulocytic and erythrocytic colonies grown in vitro had type B G-6-PD and therefore arose from presumably normal progenitors. In this study we exposed marrow cells from these same two patients to high-specific activity tritiated thymidine (3HTdR) before culture to kill cells actively synthesizing DNA. Individual granulocytic colonies were plucked and tested for G-6-PD after 14 d of culture. The frequency of type B colonies rose after exposure to 3HTdR from 8/101 to 11/36 in patient 1 and from 0/32 to 6/31 in patient 2 (P less than 0.003). No increase in the frequency of normal erythroid bursts after 3HTdR exposure was seen, implying that in PV, early granulopoiesis, and erythropoiesis are regulated differently. The results demonstrated that only type A granulocytic colonies, arising from the abnormal clone, were removed by the 3HTdR. In addition, for patient 2, statistical analysis indicated there was an absolute increase in normal granulocytic colonies detected in culture. Thus, PV clonal colony-forming units in culture (CFU-C) cycle more rapidly than do normal CFU-C and may suppress proliferation of normal CFU-C in vitro.

Cell Division

Synthesis of DNA and lecithin in tissue culture and oestrogen receptor activity in rat mammary tumours dependent on and independent of the ovary.

Dimethylbenz(alpha)anthracene (DMBA)-induced and transplanted rat mammary tumours (2 lines) were examined for oestrogen receptor activity, and for sensitivity to hormones in vivo (by ovariectomy) and in vitro (by tissue culture). In vivo, the growth of all tumours induced by the administration of DMBA in random-bred Sprague-Dawley rats was found to be dependent on the ovary, whilst in all transplanted tumours (12 TG-3 and six TG-5 lines), maintained in an inbred strain of Sprague-dawley rats, growth was found to be independent of the ovary. In vitro, the capacity for DNA synthesis in DMBA-induced tumours was better maintained after 24 h when insulin (10 microgram/ml) and corticosterone (5 microgram/ml) or insulin, corticosterone and prolactin (each 5 microgram/ml) were present in the medium (five out of 12 and eight out of 11 tumours respectively); no effect of hormones in the media was detected after 48 h. In the transplanted tumours, no effect of hormones on DNA synthesis was detected after either 24 or 48 h of culture. Synthesis of lecithin was not detectably influenced by the presence of hormones in either DMBA-induced or transplanted tumours. Oestrogen receptor concentrations were, on average, significantly higher in the DMBA-induced tumours than in either line of transplanted tumour. For 22 DMBA-induced tumours and 15 transplanted tumours, the effect of hormones in vitro ('response') was directly correlated with receptor concentration at time 0 (Spearman's rho = +0.59) and inversely correlated with the rate of DNA synthesis ('basal') at time 0 (Spearman's rho = -0.62). No single parameter or pair of parameters permitted accurate distinction between the tumour types.

9,10-Dimethyl-1,2-benzanthracene

Postnatal amino acid uptake by the rat small intestine. Changes in membrane transport systems for amino acids associated with maturation of jejunal morphology.

The uptake of a number of amino acids by the developing small intestine of the rat was investigated in vitro. L-valine, L-leucine, L-methionine, L-phenylalanine, L-arginine and L-lysine were all taken up by active transport and concentrated within the jejunal mucosa. GABA was not actively transported by the jejunum. The kinetics of carrier transport of amino acids was determined from birth to maturity. The Michaelis constant (Km) of the L-leucine, L-methionine, L-arginine and l-lysine transport systems was found to be low postnatally and increased with age, particularly after the time of weaning. The rate of l-leucine, L-methionine, L-phenylalanine and L-lysine transport (Vmax) was high postnatally but decreased after weaning. Neutral amino acids were transported at higher rates than basic amino acids. l-arginine was poorly transported by the jejunum. The specificity of transport systems for amino acids was investigated in inhibition studies. Amino acid transport systems appeared to be polyfunctional in the postnatal period but were more specific in post-weaned animals. The changes in kinetics and specificity of amino acid transport in the small intestine are discussed with reference to their possible functional significance and to the maturational changes in the jejunum, particularly with the appearance of a functionally distinct absorptive cell lining the intestinal villi during the third postnatal week (the time of weaning).

Aging