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Biomedical subjects

T O'Donnell

Publications and source records attributed to T O'Donnell.

At least 19 recordsLinked to original sources

Search for the invisible decay of neutrons with KamLAND.

The Kamioka Liquid scintillator Anti-Neutrino Detector is used in a search for single neutron or two-neutron intranuclear disappearance that would produce holes in the -shell energy level of (12)C nuclei. Such holes could be created as a result of nucleon decay into invisible modes (inv), e.g., n--> 3v or nn--> 2v. The deexcitation of the corresponding daughter nucleus results in a sequence of space and time-correlated events observable in the liquid scintillator detector. We report on new limits for one- and two-neutron disappearance: tau(n--> inv) > 5.8 x 10(29) years and tau (nn--> inv) > 1.4 x 10(30) years at 90% C.L. These results represent an improvement of factors of approximately 3 and >10(4) and over previous experiments.

Journal Article↗

Experimental investigation of geologically produced antineutrinos with KamLAND.

The detection of electron antineutrinos produced by natural radioactivity in the Earth could yield important geophysical information. The Kamioka liquid scintillator antineutrino detector (KamLAND) has the sensitivity to detect electron antineutrinos produced by the decay of 238U and 232Th within the Earth. Earth composition models suggest that the radiogenic power from these isotope decays is 16 TW, approximately half of the total measured heat dissipation rate from the Earth. Here we present results from a search for geoneutrinos with KamLAND. Assuming a Th/U mass concentration ratio of 3.9, the 90 per cent confidence interval for the total number of geoneutrinos detected is 4.5 to 54.2. This result is consistent with the central value of 19 predicted by geophysical models. Although our present data have limited statistical power, they nevertheless provide by direct means an upper limit (60 TW) for the radiogenic power of U and Th in the Earth, a quantity that is currently poorly constrained.

Journal Article↗

Noradrenergic mechanisms in the pathophysiology of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a serious psychiatric illness that may develop in individuals after exposure to a traumatic event. Recent data suggest that trauma and/or long-term stressors can cause alterations in the functioning of neuroanatomical structures and neural networks throughout the central nervous system. Specifically, dysregulation in central and perhaps, peripheral noradrenergic neural networks has been implicated as the cause of specific symptom clusters in the pathophysiology of PTSD. In this review, both clinical and preclinical data are presented to highlight types of noradrenergic dysfunction observed in individuals with PTSD. Additionally, the role of noradrenaline dysregulation in the acquisition/initiation, and maintenance of hyperarousal and reexperiencing symptom clusters in PTSD will be addressed.

Animals↗

Chronic lithium and sodium valproate both decrease the concentration of myoinositol and increase the concentration of inositol monophosphates in rat brain.

One of the mechanisms underlying lithium's efficacy as a mood stabilizer in bipolar disorder has been proposed to be via its effects on the phosphoinositol cycle (PI cycle), where it is an inhibitor of the enzyme converting inositol monophosphates to myoinositol. In contrast, sodium valproate, another commonly used mood stabilizer, appears to have no direct effects on this enzyme and was thus believed to have a different mechanism of action. In the present study, high-resolution nuclear magnetic resonance (NMR) spectroscopy was used to study the chronic effects of both lithium and sodium valproate on the concentrations of myoinositol and inositol monophosphates in rat brain. As predicted, lithium-treated rats exhibited a significant increase in the concentration of inositol monophosphates and a significant decrease in myoinositol concentration compared to saline-treated controls. However, unexpectedly, sodium valproate administration produced exactly the same results as lithium administration. These novel findings suggest that both lithium and sodium valproate may share a common mechanism of action in the treatment of bipolar disorder via actions on the PI cycle.

Animals↗

Effects of chronic lithium and sodium valproate on concentrations of brain amino acids.

The present study was designed to determine if the mood stabilizers, lithium and valproate, have common effects on concentrations of amino acid neurotransmitters which may be related to their mechanisms of action. Two separate groups of rats were administered therapeutic doses of lithium, sodium valproate, or saline for 2 weeks. Whole brain extracts were then examined using either high-field 1H NMR spectroscopy or HPLC. Both drugs decreased whole brain concentrations of aspartate, glutamate, and taurine while brain concentrations of gamma-aminobutyric acid (GABA) and alanine decreased following chronic sodium valproate administration but not following chronic lithium administration. These findings indicate that lithium and sodium valproate share common effects on the concentrations of certain amino acid neurotransmitters in whole brain which may be related to their mechanisms of action in bipolar disorder.

Alanine↗

Treatment of anaemia in the polytrauma Jehovah's Witness.

The management of Jehovah's Witnesses can prove quite challenging to the surgeon who routinely uses blood and blood products in the treatment of anaemia and hypovolaemia. The medical and legal dilemmas are exacerbated when the patient has a critically low haemoglobin level or has suffered life-threatening blood loss following polytrauma. It is essential that the treating physician should have some knowledge and understanding of the beliefs of the Jehovah's Witness in order to effectively minimise and treat blood loss. This paper reviews the ethical and medicolegal aspects involved, as well as alternatives to allogenic blood products in the treatment of anaemia in the polytrauma Jehovah's Witness patient.

Anemia↗

Development of a model for occipital fixation--validation of an analogue bone material.

Several implant systems may be used to fuse the skull to the upper cervical spine (occipitocervical fusion). Current biomechanical evaluation is restricted by the limitations of human cadaveric specimens. This paper describes the design and validation of a synthetic testing model of the occipital bone. Data from thickness measurement and pull-out strength testing of a series of human cadaveric skulls was used in the design of a high-density rigid polyurethane foam model. The synthetic occipital model demonstrated repeatable and consistent morphological and biomechanical properties. The model provides a standardized environment for evaluation of occipital implants.

Biomechanical Phenomena↗

A prospective study for evaluation of knee effusion after hip surgery.

Knee effusion is a common occurrence in elderly patients following hip surgery. We prospectively studied 106 patients undergoing proximal femoral surgery. These patients were examined pre-operatively, on days 4 and 8, and six weeks post operatively for the presence of an ipsilateral knee effusion. 71 patients had undergone Total Hip Arthroplasty (THA), 26 Dynamic Hip Screw (DHS) insertion and 9 had hemiarthroplasty. The incidence of pre-operative ipsilateral knee effusion was 13% (14 patients). 42% (44 patients) had an effusion at one week post operatively and 12% (13 patients) at 6 weeks. 57% (60 patients) of the study group had radiological evidence of osteoarthritis in their knees. However, the incidence of effusion in patients with and without arthritis was the same. The majority of these effusions resolved after six weeks with no residual effects.

Aged↗

Treatment of vinorelbine-associated tumor pain.

Vinorelbine is a synthetic vinca alkaloid used for the treatment of Hodgkin's disease and metastatic breast, non-small-cell lung, and ovarian cancers. Vinorelbine-associated tumor pain can be so severe that patients are unable to complete therapy. We present a series of three patients who were premedicated with ketorolac in an attempt to control infusion-related pain. Two of our patients responded well and were able to complete their courses of vinorelbine therapy. The third had persistently severe pain, and therapy was terminated because of pain and lack of response to vinorelbine treatment. These three cases support the hypothesis that surgery or radiation therapy before the use of vinorelbine may increase the likelihood of experiencing associated tumor pain. Premedication with ketorolac and morphine before vinorelbine infusion is proposed as a reasonable prophylactic treatment for associated tumor pain.

Adult↗

Chronic lithium and sodium valproate both decrease the concentration of myo-inositol and increase the concentration of inositol monophosphates in rat brain.

One of the mechanisms underlying lithium's efficacy as a mood stabilizer in bipolar disorder has been proposed to be via its effects on the phosphoinositol cycle (PI-cycle), where it is an inhibitor of the enzyme converting inositol monophosphates to myo-inositol. In contrast, sodium valproate, another commonly used mood stabilizer, appears to have no direct effects on this enzyme and was thus believed to have a different mechanism of action. In the present study, high resolution nuclear magnetic resonance (NMR) spectroscopy was used to study the chronic effects of both lithium and sodium valproate on the concentrations of myo-inositol and inositol monophosphates in rat brain. As predicted, lithium-treated rats exhibited a significant increase in the concentration of inositol monophosphates and a significant decrease in myo-inositol concentration compared to saline-treated controls. However, unexpectedly, sodium valproate administration produced exactly the same results as lithium administration. These novel findings suggest that both lithium and sodium valproate may share a common mechanism of action in the treatment of bipolar disorder via actions on the PI-cycle.

Animals↗

Screening for urinary tract infections in a gynaecological setting: validity and cost-effectiveness of reagent strips.

This study aims to test the validity and cost-effectiveness of reagent-strip analysis compared with microbiological laboratory testing for mass screening of urine for urinary tract infections in a gynaecological setting. Over a six-month period, urine samples from a convenient group of 228 women presenting in a gynaecological ward of an NHS Trust hospital were tested using Ames 8SG reagent strips to detect leucocyte esterase and nitrite. Total bacterial counts were also carried out; urine culture was recorded as positive if there was > 10(5) organisms/mL. Validity of the dipstick tests was measured, using four criteria (sensitivity, specificity, positive predictive value [PPV] and negative predictive value [NPV]), against the results of laboratory analysis. The combined use of the leucocyte esterase and nitrite tests produced results as follows: sensitivity, 96.4%; specificity, 88.5%; PPV, 54%; and NPV, 99.4%. Cost-effectiveness for visible costs was calculated as 48.6% for the 12.3% rate of infection in this study. The use of reagent strips in a mass-screening programme in a gynaecological setting proved both valid and cost-effective.

Cost-Benefit Analysis↗

Tritiated-naloxone binding to brainstem opioid receptors in the sudden infant death syndrome.

The sudden infant death syndrome (SIDS) is defined as the sudden death of an infant under 1 year of age that remains unexplained after a thorough case investigation, including a complete autopsy. We hypothesized that SIDS is associated with altered 3H - naloxone binding to opioid receptors in brainstem nuclei related to respiratory and autonomic control. We analyzed 3H - naloxone binding in 21 regions in SIDS and control brainstems using quantitative tissue receptor autoradiography. Three groups were analyzed: SIDS (n = 45); acute controls (n = 14); and a chronic group with oxygenation disorders (n = 15). Opioid binding was heavily concentrated in the caudal nucleus of the solitary tract, nucleus parabrachialis medialis, spinal trigeminal nucleus, inferior olive, and interpeduncular nucleus in all cases analyzed (n = 74). The arcuate nucleus on the ventral medullary surface contained negligible binding in all cases (n = 74), and therefore binding was not measurable at this site. We found no significant differences among the three groups in the age-adjusted mean 3H - naloxone binding in 21 brainstem sites analyzed. The only differences we have found to date between SIDS and acute controls are decreases in 3H - quinuclidinyl benzilate binding to muscarinic cholinergic receptors and in 3H - kainate binding to kainate receptors in the arcuate nucleus in alternate sections of this same data set. The present study suggests that there is not a defect in opioid receptor binding in cardiorespiratory nuclei in SIDS brainstems.

Autoradiography↗

Oesophagitis-induced changes in capsaicin-sensitive tachykininergic pathways in the ferret lower oesophageal sphincter.

Prolonged oesophageal acidification may impair lower oesophageal sphincter (LOS) function in reflux disease. The aim of this study was to investigate aspects of altered LOS innervation in a model of oesophagitis. Oesophagitis was induced by acid (HCl, 0.15 M) and pepsin (0.1% w/v) infusions in anaesthetized ferrets. LOS muscle strip responses to the following stimuli were measured in vitro from control and acid/pepsin-treated ferrets: electrical field stimulation (EFS; 1-50 Hz), potassium chloride KCl; 20 mM), substance P, [beta-Ala8]-neurokinin A 4-10, [Sar9, Met (O2)11]-substance P (all 10(-10) to 10(-6) M) and capsaicin (10(-8) to 10(-6) M). LOS relaxation occurred in response to all stimuli except [beta-Ala8]-neurokinin A 4-10, which evoked contraction. In muscle strips from acid/pepsin-treated animals there were no differences in amplitude or sensitivity of relaxation following EFS, KCl or substance P vs controls. However, the inhibitory response to capsaicin was increased four-fold (10(-8) M; P < 0.05) and an increased sensitivity of the inhibitory response to [Sar9, Met (O2)11]-substance P occurred (pD2 = 8.64 +/- 0.12 acid/pepsin-treated vs 7.94 +/- 0.24 control, P < 0.05). We conclude that in acute oesophagitis, increased sensitivity of capsaicin-activated inhibitory pathways occurs in which activation of NK-1 receptors plays an integral role in the ferret LOS.

Animals↗

A scientific plan for the evaluation of alternative medicine in the treatment of HIV/AIDS.

The Bastyr University AIDS Research Center was established in October 1994 through a 3-year cooperative grant with the Office of Alternative Medicine, National Institutes of Health. The mission of the Center is to (1) describe forms and patterns of use of alternative medical therapies for HIV infection and AIDS prescribed by practitioners and self-administered by HIV-positive patients in the United States, (2) screen and evaluate therapies for HIV/AIDS from five program areas of alternative medicine, and (3) provide consultation and support in the scientific evaluation of alternative therapies. To meet these goals, the Center has established a network of cooperating alternative medicine clinics and is recruiting HIV-positive men and women who are using alternative medicine to participate in the study. It is collecting data every 6 months from 1500 HIV-positive patients throughout the United States and has created a centralized database to compare outcomes (CD4+ lymphocytes, HIV RNA, CDC class progression, weight, quality of life, and survival) for a variety of alternative therapies. The Center will determine whether patients who use both conventional medicine and alternative medicine have different outcomes from patients who use only conventional medicine. The occurrence of AIDS-related opportunistic infections and neoplasms in HIV-positive patients who are using specific alternative therapies will be compared with the incidence in those who use other medical treatment. This article describes the scientific plan for the study.

Acquired Immunodeficiency Syndrome↗

Onset of menses in two adult patients with Prader-Willi syndrome treated with fluoxetine.

Prader-Willi syndrome (PWS) is characterized by hypotonia at birth, hypogonadism, early childhood obesity, and mental deficiency. Hypogonadotropic hypogonadism is a major characteristic of patients with PWS, and it is speculated to be due to hypothalamic insufficiency. Two adult female patients with PWS and no prior history of menses are presented. Both of these patients were treated with fluoxetine for psychopharmacologic management of obsessive features in the form of food preoccupation and hyperphagia or for compulsive behaviors in the form of severe self-injurious behaviors. The two female patients with PWS who had primary amenorrhea developed vaginal bleeding believed to be menses following at least 6 months of treatment with fluoxetine. Mature hypothalamic function is characterized by pulsatile release of gonadotropin-releasing hormone (GnRH) in a critical range of frequency and amplitude. Central nervous system neurotransmitters may modify GnRH secretion. Fluoxetine specifically inhibits the reuptake of serotonin which may impact the hypothalamic-pituitary-ovarian system in female patients with PWS.

Adult↗

Treatment of upper airway obstruction associated with goiter.

The authors examined the resolution of spirometric indices of upper airway obstruction (UAO) following surgical treatment for goiter. The results of a recent study suggest that the integrity of the upper airway remains intact but prolonged recovery is required.

Adult↗

Pulmonary complications of acute myelogenous leukemia.

Pulmonary complications of acute myelogenous leukemia are attributed to infection, hemorrhage, or toxicity from chemotherapeutic agents. Rarely, damaged leukemic blast cells in lung parenchyma result in chest x-ray abnormalities and respiratory symptoms.

Antineoplastic Combined Chemotherapy Protocols↗