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C Davidson

Publications and source records attributed to C Davidson.

At least 19 recordsLinked to original sources

The effect of paroxetine on 5-HT efflux in the rat dorsal raphe nucleus is potentiated by both 5-HT1A and 5-HT1B/D receptor antagonists.

Serotonin (5-HT) efflux in slices of rat dorsal raphe nucleus (DRN) was evoked by pseudo one pulse electrical stimulation (20 pulses at 100 Hz, 190 ms train duration) and measured, along with 5-HT uptake, by fast cyclic voltammetry (FCV). The selective serotonin re-uptake inhibitor (SSRI) paroxetine (10(-7) M) increased 5-HT efflux to 147 +/- 6% of pre-drug values at maximum (mean +/- SEM, n = 5) and the half-life of uptake to 443 +/- 38%. The non-selective 5-HT1 antagonist methiothepin (2 x 10(-7) M) increased 5-HT efflux to 147 +/- 9% at maximum but had no effect on uptake half-life. In contrast, (+)-WAY 100135 (10(-6) M) and GR 127935 (5 x 10(-8) M), selective antagonists at 5-HT1A and 5-HT1B/D receptors, respectively, affected neither 5-HT efflux nor uptake. When given in combination with paroxetine, the antagonists significantly increased the effect of paroxetine on efflux: methiothepin to 228 +/- 24% (P < 0.001), (+)-WAY 100135 to 212 +/- 31% (P < 0.05) and GR 127935 to 203 +/- 23% (P < 0.01). These data suggest that, under these experimental conditions, DRN 5-HT autoreceptors are tonically activated in the presence of the uptake blocker and that the antagonists act by blocking this counteracting autoinhibitory tone. The data also strongly indicate that 5-HT efflux in the rat DRN is under the control not only of 5-HT1A but also of 5-HT1B/D receptors.

Animals

Delay times in the administration of thrombolytic therapy: the Brighton experience.

We reviewed the effectiveness of a strategy involving paramedic ambulances and community education to reduce the delay to thrombolytic therapy in patients admitted with acute myocardial infarction, by analysing delay times recorded during routine treatment. Rapid identification and treatment of patients with acute myocardial infarction who were eligible for thrombolysis was carried out in the Accident and Emergency and Cardiac Care Units. Two hundred seventy-four patients were admitted with acute myocardial infarction over an 18-month period and treated with anistreplase (168) or streptokinase (106). The following median times were recorded: symptom onset to administration of thrombolytic therapy, 142 min (range 43-980 min); symptom onset to ambulance arrival, 60 min; ambulance with patient to arrival in hospital, 35 min; time to treatment in hospital ('door to needle time'), 25 min; in-hospital delays were notably shorter for patients given anistreplase as opposed to streptokinase. Shortened delays for the delivery of thrombolytic therapy can be achieved by a strategy involving public education, the availability of resuscitation ambulances, and close liaison with the Accident and Emergency Department.

Ambulances

Evidence that 5-hydroxytryptamine release in rat dorsal raphé nucleus is controlled by 5-HT1A, 5-HT1B and 5-HT1D autoreceptors.

Electrically stimulated 5-hydroxytryptamine (5-HT) release was monitored in slices of rat dorsal raphé nucleus (DRN) by fast cyclic voltammetry. Pseudo-single pulse stimulations (5 pulses at 100 Hz) were used to enable the effect of various receptor agonists to be seen without competition from endogenously released transmitter. The selective 5-HT1A receptor agonist, (+)-8-OH-DPAT (1.0 microM) decreased stimulated 5-HT release to 31 +/- 3% of controls. This decrease was inhibited by the 5-HT1A receptor antagonists, (+)-WAY-100135 (1.0 microM) and WAY-100635 (0.1 microM) but not by the 5-HT1D/B antagonist, GR127935 (0.05 microM). The selective 5-HT1B receptor agonist, CP-93129 (0.3 microM) decreased stimulated 5-HT release to 61 +/- 4% of control. This effect was antagonized by the 5-HT1B receptor antagonist, isamoltane (0.5 microM) but not by (+)-WAY-100135. The 5-HT1D agonist, sumatriptan (0.5 microM) decreased stimulated 5-HT release to 52 +/- 2% of controls. This decrease was blocked by GR-127935 but not by WAY-100635. These results suggest that 5-HT release in the rat DRN is under the control of 5-HT1A, 5-HT1B and 5-HT1D autoreceptors.

Animals

The effect of age and liver disease on the pharmacokinetics of the calcium antagonist, nisoldipine.

Two studies were performed-one in elderly, hypertensive patients and one in patients with chronic liver disease-to investigate the effect of age and liver disease upon the pharmacokinetics of nisoldipine, a dihydropyridine-type calcium antagonist. The effect of acute and chronic administration of nisoldipine (once and twice daily) was investigated in 17 elderly hypertensive patients. Compared with previously published data from young healthy volunteers, the values for Cmax and AUC appear to be higher in elderly hypertensive patients while Tmax and half-life were unchanged. Nisoldipine significantly reduced both systolic and diastolic blood pressure when given acutely to elderly hypertensive patients. Major alterations in the pharmacokinetics of nisoldipine were found in 7 patients with chronic liver disease when compared with the elderly hypertensives and healthy volunteers. The values for AUC, Cmax, half-life and volume of distribution were all higher than expected from the volunteer data while clearance was lower. One patient receiving primidone had very low nisoldipine levels, suggesting that the concomitant administration of agents that may induce the metabolism of nisoldipine should be discouraged. Nevertheless, comparisons of nisoldipine plasma levels after acute and chronic administration showed no evidence of any accumulation in either patient population in the doses used. The drug was generally well tolerated although 1 patient with chronic liver disease was withdrawn due to fluid retention.

Administration, Oral

Role of cardiorespiratory abnormalities, smoking and dive characteristics in the manifestations of neurological decompression illness.

1. Blind analysis of contrast echocardiograms to detect intracardiac shunts, blind analysis of lung function tests for evidence of small airways disease, smoking history and dive characteristics were examined in an attempt to explain neurological symptoms that occurred within 5 min of surfacing from unprovocative dives. 2. Pulmonary abnormalities were significantly more frequent in those divers without intracardiac shunts (50%) than in those with shunts (0%). Smoking was more common in those divers without shunts (55% versus 15%), although this just failed to reach conventional significance levels. Divers without shunts experienced cerebral rather than spinal symptoms after significantly shallower dives with lower tissue nitrogen loads. Depths of dives, tissue nitrogen loads and clinical manifestations in those divers without shunts were similar to the findings in divers who had symptoms after rapid ascents. Despite conservative dive profiles, clinical manifestations in divers with shunts resembled those observed after missed decompression stops. 3. The findings suggest that occult lung disease, and probably smoking, increase the risk of neurological symptoms, even after unprovocative dives, and the similarity of the dive profiles and clinical manifestations to cases with rapid ascents suggest that pulmonary barotrauma and arterial gas embolism are responsible. In divers with intracardiac shunts the different dive profiles and clinical manifestations imply that there is another mechanism, involving different tissue and bubble nitrogen kinetics resulting in venous gas liberation and peripheral amplification in embolized tissues, rather than paradoxical embolism per se.

Adult

Campylobacter fetus diarrhea in a Hutterite colony: epidemiological observations and typing of the causative organism.

Following a case of Campylobacter fetus sepsis and meningitis in a 4-month-old female member of a Hutterite colony, an epidemiological investigation revealed at least 18 cases of diarrhea in other members of the colony. C. fetus was isolated from 7 of 15 fecal samples submitted from affected persons. A case control study suggested that persons who worked in the abattoir were 2.03 times more likely to have had diarrhea, but none of the risk factors studied were significant. The epicurve of the outbreak was inconclusive as to the likely mode of spread of C. fetus. All of the C. fetus strains isolated from the blood of the infant and from the fecal samples were the same by biochemical and antibiotic susceptibility tests. Pulsed-field gel electrophoresis showed that all isolates produced identical restriction endonuclease patterns and differed from other nonepidemiologically related strains of C. fetus.

Adult

Ambulatory pressure decreases on long-term placebo treatment in older patients with isolated systolic hypertension. Syst-Eur Investigators.

OBJECTIVE: This long-term study investigated the widely accepted hypothesis that ambulatory pressure does not decrease in patients given placebo. METHODS: One hundred and twelve older (> or = 60 years) outpatients with isolated systolic hypertension were recruited. Treatment consisted of a placebo during a 3-month baseline period and long-term follow-up. RESULTS: At baseline, on placebo treatment, clinic systolic/diastolic (SBP/DBP) blood pressure (+/- SD) averaged 176 +/- 12/86 +/- 7 mmHg and 24-h SBP/DBP 151 +/- 15/81 +/- 10 mmHg. These pressures were unaltered in 51 patients in whom the baseline measurements were repeated after a further month on placebo. After the 112 patients had received placebo for 1 year (median), clinic SBP/DBP fell by 6.6 +/- 15.9 (P < 0.001)/1.4 +/- 7.4 (P = 0.06)mmHg and 24-h SBP by 2.4 +/- 10.7 mmHg (P < 0.05), whereas 24-h DBP did not change significantly. The 24-h SBP decreased more with higher baseline level and longer follow-up (5-21 months). CONCLUSIONS: These findings in older patients with isolated systolic hypertension suggest that in long-term studies the ambulatory pressure may slightly but significantly decrease on a placebo. Like those using conventional sphygmomanometry, long-term studies using non-invasive ambulatory monitoring require a placebo-controlled design.

Aged

Simultaneous "real-time" electrochemical and electrophysiological recording in brain slices with a single carbon-fibre microelectrode.

Many previous studies have demonstrated the value of carbon-fibre microelectrodes (CFMs) for single-unit activity recording and for fast cyclic voltammetry. In this report we show that these two independent methodologies can be combined at a single CFM and used to study simultaneous electrochemical and electrophysiological events in brain slices. In superfused slices of rat locus coeruleus, dorsal raphe and substantia nigra, we were able to record stable electrophysiological signals and stimulated monoamine efflux for periods of at least 2 h, thereby allowing quantitative pharmacological interventions. The simultaneous recording of amine efflux and unit activity at the same locus facilitates comparison of drug effects at pre- and post-synaptic sites. Furthermore, the system described here uses commercially available instrumentation. The circuitry is described and examples of its application are shown.

Animals

A decision aid for diagnosis of liver lesions on MRI.

Abdominal magnetic resonance imaging (MRI) plays an important role in the evaluation of liver abnormalities. The interpretation of MR images requires expert training in a rapidly changing field. DAFODILL (Decision Aid for Diagnosing Liver Lesions) is a decision-support tool designed to aid radiologists in the diagnosis of hepatic lesions seen on MRI. DAFODILL uses a knowledge base of MRI findings and a belief-network inference engine to generate probabilistic differential diagnoses of the most commonly encountered hepatic lesions. DAFODILL performs limited image processing to identify clinically relevant features, which are presented to the user for confirmation before they are used by the network. Preliminary evaluation of an initial version of the system suggests that DAFODILL may be a useful tool for radiology residents and nonexpert radiologists in interpreting MR images of the liver.

Artificial Intelligence

Histopathology of spontaneous brain herniations into the middle ear.

Two patients with spontaneous brain herniation into the middle ear have been operated on with a combined otoneurological approach. In case No. 1, two 2 x 3 mm arachnoid tissue herniations were found in the tegmen antri of the left ear. Six years later, a 8 x 9 mm mass consisting of prolapsed brain was removed from the right ear. The histological examination showed normal but disorganized nervous tissue. The surface consisted of middle ear mucosa or modified glial cells. More deeply numerous well preserved neurons and synapses were observed. In case No. 2, a 2 x 1 cm herniation was found in contact with the ossicles and the bony walls of the middle ear. The herniation consisted of partly degenerated nervous tissue which could explain the episode of temporal lobe seizure the patient experienced 8 years before surgery. In the world literature during the last 40 years, 29 cases of spontaneous or idiopathic brain herniation into the middle ear and mastoid have been reported. In 10, the herniations were multiple, as in our case No. 1. Case No. 1 is interesting also because the spontaneous brain herniation was bilateral.

Cerebrospinal Fluid Otorrhea

Very far-advanced otosclerosis.

The term very far-advanced otosclerosis is proposed to indicate otosclerotic patients with both bone and air conduction thresholds nonmeasurable on a standard clinical audiometer (blank audiogram). Three of these patients have undergone stapedotomy with satisfactory results. This confirms that cochlear implantation is not the best treatment for all profoundly deaf patients at least with implants available today. Some of the patients with a blank audiogram are better off with exploratory tympanotomy and stapedotomy.

Adult