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1.
J Small Anim Pract ; 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38679786

ABSTRACT

OBJECTIVES: To describe the diagnostic tests used and their comparative performance in dogs diagnosed with sinonasal aspergillosis in the United Kingdom. A secondary objective was to describe the signalment, clinical findings and common clinicopathologic abnormalities in sinonasal aspergillosis. MATERIALS AND METHODS: A multi-centre retrospective survey was performed involving 23 referral centres in the United Kingdom to identify dogs diagnosed with sinonasal aspergillosis from January 2011 to December 2021. Dogs were included if fungal plaques were seen during rhinoscopy or if ancillary testing (via histopathology, culture, cytology, serology or PCR) was positive and other differential diagnoses were excluded. RESULTS: A total of 662 cases were entered into the database across the 23 referral centres. Four hundred and seventy-five cases met the study inclusion criteria. Of these, 419 dogs had fungal plaques and compatible clinical signs. Fungal plaques were not seen in 56 dogs with turbinate destruction that had compatible clinical signs and a positive ancillary test result. Ancillary diagnostics were performed in 312 of 419 (74%) dogs with observed fungal plaques permitting calculation of sensitivity of cytology as 67%, fungal culture 59%, histopathology 47% and PCR 71%. CLINICAL SIGNIFICANCE: The sensitivities of ancillary diagnostics in this study were lower than previously reported challenging the clinical utility of such tests in sinonasal aspergillosis. Treatment and management decisions should be based on a combination of diagnostics including imaging findings, visual inspection, and ancillary testing, rather than ancillary tests alone.

2.
J Small Anim Pract ; 65(3): 198-205, 2024 03.
Article in English | MEDLINE | ID: mdl-37936527

ABSTRACT

OBJECTIVES: To describe the clinical presentation, diagnostic findings, surgical treatment and outcome of dogs diagnosed with parotid duct ectasia. MATERIALS AND METHODS: Medical records of dogs diagnosed with parotid duct ectasia between 2010 and 2023 at six small animal referral hospitals were retrospectively reviewed. Outcome was assessed by contacting the owners or referring veterinarians. RESULTS: Fourteen dogs were included. Lateral facial swelling was the most common clinical presentation. CT revealed a tortuous cavitary tubular fluid-filled structure consistent with a dilated parotid duct in all dogs. Surgical treatment included marsupialisation of the parotid duct papilla, surgical exploration of the duct alone, parotid duct marsupialisation with surgical exploration of the duct, parotidectomy or en-bloc parotid duct resection. The aetiology of parotid duct ectasia was not established in 13 of 14 dogs. In one case, a foreign body was retrieved from the duct. No recurrence of clinical signs was noted during the follow-up period (range 21 to 2900 days). CLINICAL SIGNIFICANCE: Parotid duct ectasia should be considered for dogs with a lateralised fluctuant non-painful tubular facial swelling. Surgical management was associated with a favourable prognosis without evidence of recurrence in all cases reported in the case series.


Subject(s)
Dog Diseases , Foreign Bodies , Dogs , Animals , Dilatation, Pathologic/surgery , Dilatation, Pathologic/veterinary , Retrospective Studies , Parotid Gland/diagnostic imaging , Parotid Gland/surgery , Foreign Bodies/veterinary , Treatment Outcome , Dog Diseases/diagnostic imaging , Dog Diseases/surgery
3.
J Small Anim Pract ; 63(2): 128-135, 2022 02.
Article in English | MEDLINE | ID: mdl-34937131

ABSTRACT

OBJECTIVES: To describe the outcome and complications associated with the use of caudal superficial epigastric axial pattern flaps in dogs and cats. MATERIAL AND METHODS: Multicentre retrospective review and descriptive study of clinical records of dogs and cats having undergone caudal superficial epigastric axial pattern flaps between 2007 and 2020. Data retrieved included signalment, aetiology of surgical defect, tumour type, presence/absence of clean surgical margins, presence/absence of post-operative wound infection, use of peri- and post-operative antibiotics, duration of anaesthesia, duration of surgery, presence and duration of hypothermia, presence and duration of hypotension, presence/absence of post-operative surgical drain and length of caudal superficial epigastric axial pattern flap. The incidence of complications and outcomes were documented. RESULTS: Seventy cases met the inclusion criteria; 51 dogs and 19 cats. In dogs, 67% of cases developed complications (59% minor, 8% major) and 33% had uneventful wound healing. In cats, 53% of cases developed complications, (47% minor, 5% major) and 47% had uneventful wound healing. In dogs, the percentage of cases experiencing dehiscence, necrosis, seroma, oedema and post-operative infection was 31%, 29%, 26%, 26% and 16% respectively. In cats, this was 26%, 16%, 11%, 0% and 5% respectively. A good overall outcome was seen in 77% of dogs and 79% of cats. A poor overall outcome was seen in 4% of dogs and 0% of cats. CLINICAL SIGNIFICANCE: Caudal superficial epigastric axial pattern flaps are traditionally thought more robust than other flaps, yet complication rates remain high, despite a high overall success rate.


Subject(s)
Cat Diseases , Dog Diseases , Animals , Cat Diseases/surgery , Cats/surgery , Dog Diseases/surgery , Dogs , Retrospective Studies , Surgical Flaps/veterinary , Treatment Outcome
4.
J Vet Cardiol ; 23: 142-148, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31174724

ABSTRACT

A 2-year, 4-month-old neutered female Labrador retriever was brought for evaluation of right-sided congestive heart failure. Echocardiographic examination revealed tricuspid valve dysplasia with only two small orifices in the valve resulting in severe tricuspid stenosis. The dog underwent a right fifth lateral intercostal thoracotomy and surgical tricuspid valvulotomy, under cardiopulmonary bypass. The stenosis was relieved by dividing the valve leaflets between the two orifices with continuation to the commissures, creating a 'bileaflet' valve. The dog made a good recovery initially, with echocardiography at 48 h after surgery showing a reduction in tricuspid valve E and A wave velocities and pressure half-time (from 230 ms to 65 ms). She was discharged five days after surgery, and spironolactone, benazepril, pimobendan, and clopidogrel were prescribed. The dog was re-presented two days later having collapsed, with pyrexia, facial swelling, and pitting edema on the ventral neck and intermandibular region. Investigations did not reveal an underlying cause, and the clinical signs resolved with supportive therapy. Two years after surgery, the dog was free of clinical signs with normal exercise tolerance and only mild tricuspid regurgitation on echocardiography, with discontinuation of all medications.


Subject(s)
Dog Diseases/surgery , Tricuspid Valve Stenosis/veterinary , Vascular Surgical Procedures/methods , Animals , Cardiopulmonary Bypass/veterinary , Dog Diseases/diagnostic imaging , Dogs , Echocardiography/veterinary , Female , Treatment Outcome , Tricuspid Valve Stenosis/diagnostic imaging , Tricuspid Valve Stenosis/surgery
6.
J Small Anim Pract ; 59(11): 670-673, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30094894

ABSTRACT

OBJECTIVES: To assess the breed-specific prevalence of, and effects of corrective airway surgery on, gastrointestinal signs in French bulldogs, English bulldogs and pugs presenting with brachycephalic airway syndrome to a referral teaching hospital. MATERIALS AND METHODS: In this retrospective study, ptyalism, regurgitation and vomiting were graded at presentation using a previously established scoring system. Staphylectomy and nares resection were performed on all dogs. Gastrointestinal signs were re-assessed via telephone follow-up at least 6 weeks after surgery. RESULTS: Ninety-eight dogs were included: French bulldogs (n=43), English bulldogs (n=12) and pugs (n=43). Overall population prevalence of all gastrointestinal signs was 56%. Breed-specific prevalence for French bulldogs was 93%, English bulldogs 58% and pugs 16%. There was post-surgical clinical improvement in gastrointestinal signs for the whole study population, especially in French bulldogs. CLINICAL SIGNIFICANCE: The prevalence of gastrointestinal signs in dogs presenting with brachycephalic airway syndrome and improvement in these clinical signs following corrective surgery may vary between breeds.


Subject(s)
Airway Obstruction/veterinary , Craniosynostoses/veterinary , Dog Diseases/diagnosis , Gastrointestinal Diseases/veterinary , Airway Obstruction/diagnosis , Airway Obstruction/surgery , Animals , Craniosynostoses/diagnosis , Dogs , Female , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/epidemiology , Male , Prevalence , Retrospective Studies , Syndrome
7.
J Small Anim Pract ; 58(9): 495-503, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28762502

ABSTRACT

OBJECTIVES: The objectives of this study were to: (1) document the incidence of surgical site dehiscence after full-thickness gastrointestinal biopsy in dogs and cats and (2) identify potential risk factors. METHODS: Data relating to dogs and cats undergoing full-thickness gastrointestinal biopsy were reviewed retrospectively following submission of a completed questionnaire by 12 referral institutions. Outcome measures were definite dehiscence, possible dehiscence (clinical records suggestive of dehiscence but not confirmed), suspected dehiscence (definite and possible combined) and death within 14 days. Logistic regression was planned for analysis of association of dehiscence with low preoperative serum albumin, biopsy through neoplastic tissue, biopsy alongside another major abdominal surgical procedure and biopsy of the colon. RESULTS: Of 172 cats, two (1·2%) had definite dehiscence, and four (2·3%) had possible dehiscence. Low preoperative serum albumin was significantly associated with definite dehiscence in univariable analysis and with suspected dehiscence and death within 14 days in univariable analysis, but all odds ratios had wide 95% confidence intervals. A histopathological diagnosis of neoplasia was significantly associated with death within 14 days in univariable analysis. Of 195 dogs, two (1·0%) had definite dehiscence, and three (1·5%) had possible dehiscence. In dogs, there was no association between any outcome measure and the putative risk factors. CLINICAL SIGNIFICANCE: Incidence of dehiscence following full-thickness gastrointestinal biopsy was low in this study. When determining the appropriateness of biopsy in individual cases, this information should be balanced against the potentially life-threatening consequences of dehiscence.


Subject(s)
Cats/surgery , Digestive System Surgical Procedures/veterinary , Dogs/surgery , Surgical Wound Dehiscence/veterinary , Abdomen , Animals , Biopsy/methods , Biopsy/veterinary , Incidence , Retrospective Studies , Risk Factors , Surgical Wound Dehiscence/epidemiology
8.
J Obstet Gynaecol ; 33(6): 601-4, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23919859

ABSTRACT

A questionnaire-based study was undertaken to assess women's satisfaction with the home medical abortion service. Over a 15-month period, questionnaires were conducted at 24 h and 2 weeks following the procedure. A total of 127 women took part in the study and filled in a questionnaire at 24 h, with 77 completing the questionnaire at 2 weeks. At 24 h, over 95% of women who responded, agreed or strongly agreed that they felt prepared for the pain and bleeding that they experienced at home. At 2 weeks, 97.3% of respondents felt that they had had enough information and knew what to expect, and were therefore satisfied with the procedure. Only 15% of women were lost to clinical follow-up at 2 weeks. The majority of women are satisfied with the home medical abortion service. These high satisfaction rates are maintained at 2 weeks. Telephone follow-up 2 weeks after the abortion was safe and effective.


Subject(s)
Abortion, Induced , Patient Satisfaction/statistics & numerical data , Abortifacient Agents, Nonsteroidal/administration & dosage , Abortifacient Agents, Nonsteroidal/adverse effects , Abortifacient Agents, Steroidal/administration & dosage , Abortifacient Agents, Steroidal/adverse effects , Female , Humans , Mifepristone/administration & dosage , Mifepristone/adverse effects , Misoprostol/administration & dosage , Misoprostol/adverse effects , Pregnancy Tests , Self Care , Surveys and Questionnaires , Telephone , United Kingdom
9.
Domest Anim Endocrinol ; 43(3): 260-3, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22560177

ABSTRACT

In this study, total RNA was collected from abdominal adipose tissue samples obtained from 10 broiler chickens at 3, 4, 5, and 6 wk of age and prepared for quantitative real-time PCR analysis. Quantitative real-time PCR analysis was used to examine the influence of age on the expression of the adipose tissue genes for IL-1ß, -6, -10, -15, -18; brain-derived neurotropic factor; ciliary neurotropic factor; interferon γ, neuropeptide Y receptor Y1; neuropeptide Y; nucleobindin 2; growth hormone receptor; leptin receptor; and visfatin. Between 3 and 6 wk of age, leptin receptor expression decreased (P=0.013) with age, whereas expression of IL-15 (P=0.015) and growth hormone receptor (P=0.002) increased. Furthermore, IL-18 (P<0.001) and visfatin (P=0.007) expression increased between 4 and 6 wk of age. This is a unique exhibition of age-related changes in cytokine gene expression in chicken adipose tissue. Future studies are needed to elucidate the role of adipose tissue cytokines in growth and, possibly, disease resistance.


Subject(s)
Adipose Tissue/metabolism , Chickens/metabolism , Interleukins/metabolism , Neuropeptides/metabolism , Receptors, Leptin/metabolism , Receptors, Somatotropin/metabolism , Animals , Chickens/genetics , Chickens/growth & development , Female , Gene Expression Regulation, Developmental/physiology , Interleukins/genetics , Male , Neuropeptides/genetics , RNA/genetics , RNA/metabolism , Real-Time Polymerase Chain Reaction , Receptors, Leptin/genetics , Receptors, Somatotropin/genetics
10.
Transfus Med ; 12(3): 173-9, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12071873

ABSTRACT

We evaluated the effectiveness, ease of use and safety of five machines for blood salvage during coronary artery surgery. All were equally effective in concentrating red cells. We measured haemoglobin, packed cell volume, free haemoglobin, white cells, neutrophil elastase, platelets, thrombin-antithrombin complex (TAT), prothrombin activation peptide F1.2, fibrin degradation product (d-dimers), tissue plasminogen activator (tPA) and heparin in wound blood, in washed cell suspensions and in a unit of bank blood prepared for each patient. All machines were equally safe and easy to use and were equally effective in removing heparin and the physiological components measured. There were no adverse effects on patients. Clotting factors are severely depleted both in salvaged blood, even before washing, and in bank blood. Cell savers are a valuable adjunct to coronary artery surgery, but careful monitoring of coagulation is required when the volumes of either bank blood or salvaged blood are large.


Subject(s)
Blood Loss, Surgical/prevention & control , Cardiopulmonary Bypass/instrumentation , Myocardial Revascularization/instrumentation , Adult , Aged , Aged, 80 and over , Blood Transfusion, Autologous/instrumentation , Cardiopulmonary Bypass/adverse effects , Female , Hematocrit , Hematologic Tests , Hemoglobins/analysis , Humans , Male , Middle Aged , Myocardial Revascularization/adverse effects
11.
Life Support Biosph Sci ; 8(1): 23-31, 2001.
Article in English | MEDLINE | ID: mdl-11725782

ABSTRACT

Ammonium ions are byproducts of the oxidation of nitrogen-containing substances occurring in the initial treatment steps of water recovery systems. Removal of ammonium ions from the effluent stream from 1000 ppm to less than 0.25 ppm is an imperative need as a part of the space life support infrastructure. Drawbacks associated with processes proposed in the past include the generation of a secondary waste, cost, size, and/or the use of consumables that need to be stored or supplied. Lynntech has developed a technology that is based on an innovative, environmentally friendly electrochemical process for the effective removal of ammonium ions. The process does not use consumables except for oxygen gas from air, and does not generate a secondary waste. By controlling operational conditions, the ammonium ions may be transformed to nitrogen gas and/or to nitrate ions. Other advantages of the process include: it is energy efficient, operates at room temperature, and is microgravity compatible. Grant numbers: NAS9-00013.


Subject(s)
Bioreactors , Life Support Systems/instrumentation , Quaternary Ammonium Compounds/chemistry , Space Flight/instrumentation , Water Purification/methods , Dialysis , Electrochemistry , Electrolysis , Equipment Design , Evaluation Studies as Topic , Life Support Systems/economics , Nitrates/chemistry , Nitrogen/chemistry , Oxidation-Reduction , Space Flight/economics , Weightlessness
12.
Life Support Biosph Sci ; 8(1): 33-41, 2001.
Article in English | MEDLINE | ID: mdl-11725783

ABSTRACT

In spacecraft water recovery systems there is a need to develop a postprocessor water polishing system to remove organic impurities to levels below 250 micrograms/L (ppb) with a minimum use of expendables. This article addresses the development of a photocatalytic process as a postprocessor water polishing system that is microgravity compatible, operates at room temperature, and requires only a minimal use of both oxygen gas (or air) and electrical power for low energy UV-A (315-400 nm) lamps. In the photocatalytic process, organic contaminants are degraded to benign end products on semiconductor surfaces, usually TiO2. Some challenging issues related to the use of TiO2 for the degradation of organic contaminants have been addressed. These include: i) efficient and stable catalytic material; ii) immobilization of the catalyst to produce a high surface area material that can be used in packed-bed reactors, iii) effective light penetration, iv) effective, microgravity-compatible, oxidant delivery; v) reduced pressure drop, and vi) minimum retention time. The research and development performed on this photocatalytic process is presented in detail. Grant numbers: NAS9-97182.


Subject(s)
Life Support Systems/instrumentation , Space Flight/instrumentation , Titanium/chemistry , Water Purification/methods , Weightlessness , Catalysis , Ecological Systems, Closed , Evaluation Studies as Topic , Ions , Light , Organic Chemicals/chemistry , Photochemistry , Spacecraft/instrumentation , Ultraviolet Rays , Water Pollutants, Chemical , Water Purification/instrumentation
13.
Environ Sci Technol ; 35(1): 216-21, 2001 Jan 01.
Article in English | MEDLINE | ID: mdl-11352016

ABSTRACT

A method has been developed for removing chromium from alkaline high-level radioactive tank waste. Removing chromium from these wastes is critical in reducing the volume of waste requiring expensive immobilization and deep geologic disposition. The method developed is based on the oxidation of insoluble chromium(III) compounds to soluble chromate using ferrate. This method could be generally applicable to removing chromium from chromium-contaminated solids, when coupled with a subsequent reduction of the separated chromate back to chromium(III). The tests conducted with a simulated Hanford tank sludge indicate that the chromium removal with ferrate is more efficient at 5 M NaOH than at 3 M NaOH. Chromium removal increases with increasing Fe(VI)/Cr(II) molar ratio, but the chromium removal tends to level out for Fe(VI)/ Cr(III) greaterthan 10. Increasingtemperature leadsto better chromium removal, but higher temperatures also led to more rapid ferrate decomposition. Tests with radioactive Hanford tank waste generally confirmed the simulant results. In all cases examined, ferrate enhanced the chromium removal, with a typical removal of around 60-70% of the total chromium present in the washed sludge solids. The ferrate leachate solutions did not contain significant concentrations of transuranic elements, so these solutions could be disposed as low-activity waste.


Subject(s)
Chromium/isolation & purification , Iron , Radioactive Waste/analysis , Hydrogen-Ion Concentration , Methods , Sodium Hydroxide , Temperature , Washington
14.
Thromb Haemost ; 85(2): 195-7, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11246531

ABSTRACT

A 66 year old male, referred for cardiac surgery, was found to have high molecular weight kininogen deficiency (activity <1%). Apart from activated partial thromboplastin time (APTT) >300 s, tests of haemostasis were otherwise normal (factors VIII, IX, XI, XII and prekallikrein). No inhibitor of coagulation was found. The activated coagulation time (ACT) was 800 s pre-operatively and >1000 s after heparin. Heparin levels were measured directly by an anti-Xa chromogenic assay, with values of between 2.9 and 3.2 u/ml during cardiopulmonary bypass. Thrombin-antithrombin levels rose from 2.3*g/l before surgery to a peak of 83.5*g/l at the end of cardiopulmonary bypass. Cross linked fibrin d-dimers (XDP) levels rose from 100 ng/ml before operation to 600 ng/ml after protamine administration. The patient had no excess bleeding and no thrombotic complications from surgery. This patient shows that high molecular weight kininogen is not required for thrombin formation or fibrinolysis during cardiac surgery and illustrates the need to measure heparin directly in patients with such contact factor deficiencies.


Subject(s)
Kininogen, High-Molecular-Weight/deficiency , Aged , Blood Coagulation Tests/standards , Cardiac Surgical Procedures/standards , Drug Monitoring , Heparin/blood , Humans , Kininogen, High-Molecular-Weight/blood , Male , Whole Blood Coagulation Time
15.
Learn Mem ; 6(3): 284-91, 1999.
Article in English | MEDLINE | ID: mdl-10492010

ABSTRACT

Neocortical pyramidal neurons respond to prolonged activity blockade by modulating their balance of inward and outward currents to become more sensitive to synaptic input, possibly as a means of homeostatically regulating firing rates during periods of intense change in synapse number or strength. Here we show that this activity-dependent regulation of intrinsic excitability depends on the neurotrophin brain-derived neurotrophic factor (BDNF). In experiments on rat visual cortical cultures, we found that exogenous BDNF prevented, and a TrkB-IgG fusion protein reproduced, the change in pyramidal neuron excitability produced by activity blockade. Most of these effects were also observed in bipolar interneurons, indicating a very general role for BDNF in regulating neuronal excitability. Moreover, earlier work has demonstrated that BDNF mediates a different kind of homeostatic plasticity present in these same cultures: scaling of the quantal amplitude of AMPA-mediated synaptic inputs up or down as a function of activity. Taken together, these results suggest that BDNF may be the signal controlling a coordinated regulation of synaptic and intrinsic properties aimed at allowing cortical networks to adapt to long-lasting changes in activity.


Subject(s)
Brain-Derived Neurotrophic Factor/physiology , Cerebral Cortex/physiology , Neurons/physiology , Animals , Brain Chemistry/physiology , Brain-Derived Neurotrophic Factor/metabolism , Cerebral Cortex/cytology , Electrophysiology , In Vitro Techniques , Membrane Potentials/physiology , Neuronal Plasticity/drug effects , Neurons/metabolism , Patch-Clamp Techniques , Rats , Synapses/physiology , Tetrodotoxin/pharmacology , Visual Cortex/cytology , Visual Cortex/physiology , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology
16.
Nat Neurosci ; 2(6): 515-20, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10448215

ABSTRACT

During learning and development, the level of synaptic input received by cortical neurons may change dramatically. Given a limited range of possible firing rates, how do neurons maintain responsiveness to both small and large synaptic inputs? We demonstrate that in response to changes in activity, cultured cortical pyramidal neurons regulate intrinsic excitability to promote stability in firing. Depriving pyramidal neurons of activity for two days increased sensitivity to current injection by selectively regulating voltage-dependent conductances. This suggests that one mechanism by which neurons maintain sensitivity to different levels of synaptic input is by altering the function relating current to firing rate.


Subject(s)
Cerebral Cortex/physiology , Neuronal Plasticity/physiology , Pyramidal Cells/physiology , Animals , Animals, Newborn/physiology , Cells, Cultured , Cerebral Cortex/cytology , Electric Conductivity , Electrophysiology , Ions , Rats
17.
Neuron ; 21(3): 521-30, 1998 Sep.
Article in English | MEDLINE | ID: mdl-9768839

ABSTRACT

Recently, we have identified a novel form of synaptic plasticity that acts to stabilize neocortical firing rates by scaling the quantal amplitude of AMPA-mediated synaptic inputs up or down as a function of neuronal activity. Here, we show that the effects of activity blockade on quantal amplitude are mediated through the neurotrophin brain-derived neurotrophic factor (BDNF). Exogenous BDNF prevented, and a TrkB-IgG fusion protein reproduced, the effects of activity blockade on pyramidal quantal amplitude. BDNF had opposite effects on pyramidal neuron and interneuron quantal amplitudes and modified the ratio of pyramidal neuron to interneuron firing rates. These data demonstrate a novel role for BDNF in the homeostatic regulation of excitatory synaptic strengths and in the maintenance of the balance of cortical excitation and inhibition.


Subject(s)
Brain-Derived Neurotrophic Factor/pharmacology , Interneurons/physiology , Pyramidal Cells/physiology , Synapses/physiology , Visual Cortex/physiology , Animals , Cells, Cultured , Excitatory Postsynaptic Potentials/drug effects , Excitatory Postsynaptic Potentials/physiology , Gene Expression Regulation/drug effects , Humans , Immunoglobulin G/biosynthesis , Interneurons/drug effects , Models, Neurological , Pyramidal Cells/drug effects , Quantum Theory , Rats , Receptor Protein-Tyrosine Kinases/biosynthesis , Receptor Protein-Tyrosine Kinases/genetics , Receptor, Ciliary Neurotrophic Factor , Receptors, Nerve Growth Factor/biosynthesis , Receptors, Nerve Growth Factor/genetics , Recombinant Fusion Proteins , Recombinant Proteins/pharmacology , Synapses/drug effects , Tetrodotoxin/pharmacology , Visual Cortex/cytology , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology , gamma-Aminobutyric Acid/pharmacology
18.
Nature ; 391(6670): 892-6, 1998 Feb 26.
Article in English | MEDLINE | ID: mdl-9495341

ABSTRACT

Information is stored in neural circuits through long-lasting changes in synaptic strengths. Most studies of information storage have focused on mechanisms such as long-term potentiation and depression (LTP and LTD), in which synaptic strengths change in a synapse-specific manner. In contrast, little attention has been paid to mechanisms that regulate the total synaptic strength of a neuron. Here we describe a new form of synaptic plasticity that increases or decreases the strength of all of a neuron's synaptic inputs as a function of activity. Chronic blockade of cortical culture activity increased the amplitude of miniature excitatory postsynaptic currents (mEPSCs) without changing their kinetics. Conversely, blocking GABA (gamma-aminobutyric acid)-mediated inhibition initially raised firing rates, but over a 48-hour period mESPC amplitudes decreased and firing rates returned to close to control values. These changes were at least partly due to postsynaptic alterations in the response to glutamate, and apparently affected each synapse in proportion to its initial strength. Such 'synaptic scaling' may help to ensure that firing rates do not become saturated during developmental changes in the number and strength of synaptic inputs, as well as stabilizing synaptic strengths during Hebbian modification and facilitating competition between synapses.


Subject(s)
Neuronal Plasticity/physiology , Pyramidal Cells/physiology , Synaptic Transmission/physiology , Visual Cortex/physiology , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism , 2-Amino-5-phosphonovalerate/pharmacology , Animals , Bicuculline/pharmacology , Cells, Cultured , Excitatory Amino Acid Antagonists/pharmacology , GABA Antagonists/pharmacology , Glutamic Acid/pharmacology , Membrane Potentials , Pyramidal Cells/cytology , Rats , Receptors, N-Methyl-D-Aspartate/drug effects , Receptors, N-Methyl-D-Aspartate/metabolism , Tetrodotoxin/pharmacology , Visual Cortex/cytology
19.
J Neurosci ; 17(12): 4527-35, 1997 Jun 15.
Article in English | MEDLINE | ID: mdl-9169513

ABSTRACT

The excitability of cortical circuits is modulated by interneurons that release the inhibitory neurotransmitter GABA. In primate and rodent visual cortex, activity deprivation leads to a decrease in the expression of GABA. This suggests that activity is able to adjust the strength of cortical inhibition, but this has not been demonstrated directly. In addition, the nature of the signal linking activity to GABA expression has not been determined. Activity is known to regulate the expression of the neurotrophin brain-derived neurotrophic factor (BDNF), and BDNF has been shown to influence the phenotype of GABAergic interneurons. We use a culture system from postnatal rat visual cortex to test the hypothesis that activity is regulating the strength of cortical inhibition through the regulation of BDNF. Cultures were double-labeled against GABA and the neuronal marker MAP2, and the percentage of neurons that were GABA-positive was determined. Blocking spontaneous activity in these cultures reversibly decreased the number of GABA-positive neurons without affecting neuronal survival. Voltage-clamp analysis of inhibitory currents demonstrated that activity blockade also decreased GABA-mediated inhibition onto pyramidal neurons and raised pyramidal neuron firing rates. All of these effects were prevented by incubation with BDNF during activity blockade, but not by neurotrophin 3 or nerve growth factor. Additionally, blockade of neurotrophin signaling mimicked the effects of activity blockade on GABA expression. These data suggest that activity regulates cortical inhibition through a BDNF-dependent mechanism and that this neurotrophin plays an important role in the control of cortical excitability.


Subject(s)
Brain-Derived Neurotrophic Factor/pharmacology , Nerve Growth Factors/pharmacology , Neurons/physiology , Receptors, Nerve Growth Factor/physiology , Visual Cortex/physiology , gamma-Aminobutyric Acid/metabolism , Animals , Animals, Newborn , Carbazoles/pharmacology , Cell Survival/drug effects , Cells, Cultured , Indole Alkaloids , Interneurons/drug effects , Interneurons/physiology , Membrane Potentials/drug effects , Microtubule-Associated Proteins/biosynthesis , Neurons/cytology , Neurons/drug effects , Neurotrophin 3 , Patch-Clamp Techniques , Pyramidal Cells/drug effects , Pyramidal Cells/physiology , Rats , Receptors, Nerve Growth Factor/antagonists & inhibitors , Signal Transduction , Tetrodotoxin/pharmacology , Visual Cortex/cytology
20.
Aust N Z J Surg ; 67(12): 846-8, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9451338

ABSTRACT

BACKGROUND: Melanoma occurring in the anorectal region is recognized to be an uncommon tumour with a poor prognosis. Queensland has the highest incidence rate of cutaneous melanoma in the world. The purpose of the present study was to determine if the very high incidence of cutaneous melanoma in Queensland has any bearing on the incidence of anorectal melanoma, and to compare this with published studies from other parts of the world. An assessment of the authors' results in the treatment of anorectal melanoma was made by a review of patients presenting during the last decade throughout Queensland. METHODS: All cases of melanoma occurring in Queensland are accumulated in the Melanoma Register, administered by the Queensland Melanoma Project, and data from this were used to derive the results in the present study. Queensland population data were provided by the Australian Bureau of Statistics. RESULTS: During the study period 1985-95 in Queensland there were 21,391 cases of cutaneous melanoma which occurred in an average population, during that time, of 2.89 million. During the same time there were nine cases of anorectal melanoma, giving a relative incidence therefore of 0.04%. This contrasts with published relative incidences of 0.2% for white people in North America, 11% for Southwestern Native Americans, and 14.2% for Northern Pakistan (P < 0.0001). However, the population-based incidence rates of anorectal melanoma for Queensland, United States white people, Southwestern Native Americans and Northern Pakistan are not significantly different from each other. All patients in the present series presented with large tumours, and none survived beyond 25 months despite standard surgical and adjuvant therapy. CONCLUSIONS: The protection against cutaneous melanoma afforded by skin pigmentation is not apparent in the anal area. Anorectal melanoma is no more or less frequent in Queensland, even with the very high incidence rate of cutaneous melanoma. Sun exposure appears to be neither protective nor a risk factor. The outcome of therapy for this condition remains disappointing in the authors' experience.


Subject(s)
Anus Neoplasms/epidemiology , Melanoma/epidemiology , Rectal Neoplasms/epidemiology , Adult , Aged , Anus Neoplasms/mortality , Anus Neoplasms/surgery , Female , Humans , Incidence , Male , Melanoma/mortality , Melanoma/surgery , Middle Aged , Prognosis , Queensland/epidemiology , Rectal Neoplasms/mortality , Rectal Neoplasms/surgery , Skin Neoplasms/epidemiology , Sunlight/adverse effects , Survival Rate
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