Search PubMed⌕ Search

Biomedical subjects

C B Johnson

Publications and source records attributed to C B Johnson.

At least 19 recordsLinked to original sources

Depression of NMDA-receptor-mediated segmental transmission by ketamine and ketoprofen, but not L-NAME, on the in vitro neonatal rat spinal cord preparation.

Activation of spinal N-methyl-D-aspartate (NMDA) receptors and then the nitric oxide and the arachidonic acid pathways is important in pain transmission. This study assessed the effects of the NMDA receptor channel blocker ketamine, the nitric oxide synthase inhibitor L-NAME, and the cyclooxygenase inhibitor ketoprofen in nociceptive transmission using an in vitro neonatal rat spinal cord preparation. Supramaximal electrical stimulation of the dorsal root evoked the A-fibre- and C-fibre-mediated high intensity excitatory postsynaptic potential (EPSP) in the ipsilateral ventral root. Low intensity stimulation evoked the A-fibre-mediated monosynaptic compound action potential (MSR) superimposed on the low intensity EPSP. Both the low intensity EPSP and the high intensity EPSP contain NMDA-receptor-mediated components. Only ketamine and ketoprofen depressed the synaptic responses. Ketamine depressed all three spinal reflexes with IC(50) values (with 95% CI) of 10.80 microM (5.97 to 19.54 microM) for the MSR, 8.29 microM (4.53 to 14.17 microM) for the low intensity EPSP, and 5.35 microM (3.05 to 9.40 microM) for the high intensity EPSP. Ketoprofen depressed the low intensity EPSP and the high intensity EPSP only; IC(50) values (with 95% CI) were 354.5 microM (217.5 to 576.8 microM) and 302.7 microM (174.0 to 526.7 microM), respectively. Reflexes recovered after drug washout. These data demonstrated that ketamine and ketoprofen, but not L-NAME, depressed NMDA-mediated nociceptive transmission in spinal cord preparations from neonatal rats.

Afferent Pathways↗

Neurophysiological techniques to assess pain in animals.

Neurophysiological techniques are widely applied to animals, both in the search as a monitor for adequacy of anaesthesia, and studies to assess the efficacy of analgesic agents. Laboratory animals have been extensively used in models to investigate pain in man. However a substantial number of studies have also used neurophysiological techniques to increase knowledge of pain in specific animal species, with the aim of improving animal welfare. This review provides an overview of neurophysiological techniques involving the brain that have been used in the assessment of pain in animals. An explanation of the methodology of EEG recording, with particular emphasis on veterinary studies, is given. Neurophysiological models developed to assess pain in different species are described, and their relevance to advancements in animal welfare or best clinical practice indicated.

Animal Welfare↗

Cerebellar cortical abiotrophy in Wiltshire sheep.

AIM: To investigate the nature of a neurological disease in Wiltshire sheep. METHODS: Three affected lambs were examined, humanely killed and necropsied. Selected neurological tissues were examined by light and electron microscopy. RESULTS: Primary neurological lesions were confined to the cerebellum and were characterised by loss of Purkinje cells and the presence of large hypertrophied dendrites of surviving Purkinje cells. These contained stacks of smooth endoplasmic reticulum. There was hyperplasia and cell swelling of Bergmann glia. Mild Wallerian-type degeneration affected white matter in the cerebellum and spinal cord. CONCLUSION: The cerebellar lesions were of a degenerative and reactive rather than hypoplastic nature. These, and the history, suggest a genetic cause with putative inheritance as an autosomal recessive trait. Accordingly, the disorder is described as a cerebellar abiotrophy.

Animals↗

Effects of age on the electroencephalographic response to castration in lambs anaesthetised using halothane in oxygen.

AIM: To use the electroencephalogram (EEG) to ascertain whether the response of the cerebral cortex to the noxious stimulus of castration varied with age in lambs. METHODS: Two groups of East Friesian lambs were selected according to age; the mean age of the younger group (n=21) was 12 (SD 2) days and the older group (n=20) was 29 (SD 1) days. Anaesthesia was induced via mask using 4% halothane in oxygen, and maintained using 1.5% halothane in oxygen at a flow rate of 4 L/min. Once a stable plane of anaesthesia had been achieved, data collection of EEG and electrocardiographic (ECG) readings commenced, and the lambs were castrated 15 min later, using rubber rings. Median and 95% spectral edge frequencies (F95) and total EEG power (ptot) were derived from data from the EEG. RESULTS: Following castration, there was an increase in the median frequency (F50) in the younger lambs (p=0.002), and an increase in ptot in both groups (p=0.05), which was of greater magnitude in the older lambs. There were no significant changes in the F95. Both younger and older lambs exhibited a transient bradycardia (p=0.001 and p=0.01, respectively). CONCLUSIONS: These differences in the cortical response between the two groups suggest that 2-week-old lambs undergo a qualitatively different perception of the noxious stimulus of castration compared to 4-week-old lambs.

Age Factors↗

Effects of midazolam and sarmazenil on the equine electroencephalogram during anaesthesia with halothane in oxygen.

The electroencephalographic (EEG) effects of a rapid infusion of midazolam and sarmazenil following a bolus of midazolam were investigated in eight Welsh mountain ponies anaesthetized with 0.8% halothane in oxygen. The peak plasma concentration of midazolam was 2.13 +/- 0.34 ng/mL (mean +/- SD) occurring 5 min after the start of the infusion. Sarmazenil concentrations were not measured. The 95% spectral edge frequency of the EEG decreased by a maximum of 39.8 +/- 15.8%, 10 min after the start of the midazolam infusion. No changes were seen in median frequency of the EEG or the second differential of the middle latency auditory evoked response. The variability of median frequency (F50) and spectral edge frequency (F95) were reduced by a maximum of 80 +/- 7 and 84 +/- 7%, respectively. The sarmazenil infusion reversed the effects of a bolus of midazolam on the variability of F50 and the magnitude and variability of F95. The second differential of the middle latency auditory evoked potential (DD) was increased by 56.4 +/- 69.3%, 10 min after the start of the sarmazenil infusion. There were no statistically significant differences in EEG variables between the baseline of the midazolam infusion and 10 min after the start of the sarmazenil infusion. Midazolam infusion resulted in specific and unusual changes in the EEG of anaesthetized ponies. These changes were completely reversed by sarmazenil infusion. The data presented suggest that sarmazenil has no intrinsic effect upon the EEG.

Anesthesia↗

Comparison of detomidine and romifidine as premedicants before ketamine and halothane anesthesia in horses undergoing elective surgery.

OBJECTIVE: To compare detomidine hydrochloride and romifidine as premedicants in horses undergoing elective surgery. ANIMALS: 100 client-owned horses. PROCEDURE: After administration of acepromazine (0.03 mg/kg, IV), 50 horses received detomidine hydrochloride (0.02 mg/kg of body weight, IV) and 50 received romifidine (0.1 mg/kg, IV) before induction and maintenance of anesthesia with ketamine hydrochloride (2 mg/kg) and halothane, respectively. Arterial blood pressure and blood gases, ECG, and heart and respiratory rates were recorded. Induction and recovery were timed and graded. RESULTS: Mean (+/- SD) duration of anesthesia for all horses was 104 +/- 28 minutes. Significant differences in induction and recovery times or grades were not detected between groups. Mean arterial blood pressure (MABP) decreased in both groups 30 minutes after induction, compared with values at 10 minutes. From 40 to 70 minutes after induction, MABP was significantly higher in detomidine-treated horses, compared with romifidine-treated horses, although more romifidine-treated horses received dobutamine infusions. In all horses, mean respiratory rate ranged from 9 to 11 breaths/min, PaO2 from 200 to 300 mm Hg, PaCO2 from 59 to 67 mm Hg, arterial pH from 7.33 to 7.29, and heart rate from 30 to 33 beats/min, with no significant differences between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Detomidine and romifidine were both satisfactory premedicants. Romifidine led to more severe hypotension than detomidine, despite administration of dobutamine to more romifidine-treated horses. Both detomidine and romifidine are acceptable alpha2-adrenoceptor agonists for use as premedicants before general anesthesia in horses; however, detomidine may be preferable when maintenance of blood pressure is particularly important.

Adrenergic alpha-2 Receptor Agonists↗

Multidrug resistance-1 gene expression does not increase during tumor progression in the MGH-OGS murine osteosarcoma tumor model.

In addition to its possible role in drug resistance, expression of the multidrug resistance-1 gene may also be associated with a more malignant phenotype and tumor progression. This study evaluated its expression during tumor progression in the MGH-OGS transplantable murine osteosarcoma tumor model. Three variables of tumor progression were analyzed: tumor size, local recurrence, and metastasis. With a highly sensitive reverse transcription-polymerase chain reaction method, mRNA levels of multidrug resistance-1 were compared in primary tumors of different sizes. In addition, the levels were compared in primary, locally recurrent, and metastatic tumors isolated from individual mice. No significant difference was found in the levels of expression with increasing primary tumor size. In addition, the levels in primary, locally recurrent, and metastatic tumors were not significantly different. Our results indicate that--at least in the MGH-OGS tumor model, which is analogous to the majority of spontaneously occurring human osteosarcomas in that it has low levels of multidrug resistance-1/P-glycoprotein and is sensitive to doxorubicin--there is no evidence of upregulation of multidrug resistance-1 expression during tumor progression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Comparison of detomidine/ketamine and guaiphenesin/thiopentone for induction of anaesthesia in horses maintained with halothane.

This prospective clinical study compared the physiological effects of two commonly used anaesthetic induction techniques in horses maintained with halothane. One hundred horses admitted for elective surgery were randomly allocated to receive either guaiphenesin (to effect) and thiopentone (5 mg/kg), or detomidine (20 microg/kg) and ketamine (2 mg/kg) for the induction of anaesthesia after acepromazine premedication. Anaesthesia was maintained with halothane in oxygen. There were no significant differences in breed, age, sex, weight, type of surgery and duration of anaesthesia between the groups. Immediately after induction of anaesthesia heart rate was higher after guaiphenesin and thiopentone, and arterial blood pressure was higher after detomidine and ketamine. Thereafter hypotension, often necessitating an infusion of dobutamine, developed in both groups. Arterial blood gases and respiratory rates were similar in the two groups. There were no significant differences between the groups in the subjectively scored quality of induction and recovery, or in recovery time.

Analgesics↗

Comparison of the effects of halothane, isoflurane and methoxyflurane on the electroencephalogram of the horse.

We have investigated in eight ponies the effects of three different end-tidal concentrations of halothane, isoflurane and methoxyflurane on median (F50) and 95% spectral edge (F95) frequencies of the EEG and the second differential (DD) of the middle latency auditory evoked potential (MLAEP). The three concentrations of each agent were chosen to represent approximately the minimum alveolar concentration (MAC), 1.25 MAC and 1.5 MAC for each agent. During halothane anaesthesia, F95 decreased progressively as halothane concentration increased, from mean 13.9 (SD 2.6) at 0.8% to 11.9 (1.1) at 1.2%. DD was lower during anaesthesia with the highest concentration (21 (6.5)) compared with the lowest (27.6 (11.4)). There were no significant changes in F50. During isoflurane anaesthesia, there was a small, but significant increase in F95 between the intermediate and highest concentrations (10.2 (1.5) to 10.8 (1.6)). There were no changes in F50 and DD. Values of F95, F50 and DD at all isoflurane concentrations were similar to those of halothane at the highest concentration. During methoxyflurane anaesthesia, F95 and F50 decreased progressively as methoxyflurane concentration was increased, from 21.3 (0.7) and 6.5 (1), respectively, at 0.26%, to 20.1 (0.6) and 5.6 (0.8), respectively, at 0.39%. DD was lower during anaesthesia with the highest concentration of methoxyflurane (25.7 (7.8)) compared with the lowest (39.7 (20.6)). Values of F95, F50 and DD at all methoxyflurane concentrations were higher than those seen with halothane at the lowest concentration. The different relative positions of the dose-response curves for EEG and MLAEP changes compared with antinociception (MAC) changes suggest differences in the mechanisms of action of these three agents. These differences may explain the incomplete adherence to the Meyer-Overton rule.

Anesthetics, Inhalation↗

Hospice: what gets in the way of appropriate and timely access.

Although hospice is viewed as highly effective in managing a good death, this service remains on the fringe of traditional medical care and is underutilized in the United States today. The same reimbursement criteria that facilitate access to hospice care for many also create barriers for others or exclude them altogether. The article examines who is and who is not receiving hospice care and why. Interventions and corrective actions are proposed.

Community-Institutional Relations↗

Cardiovascular effects of surgical castration during anaesthesia maintained with halothane or infusion of detomidine, ketamine and guaifenesin in ponies.

Sixteen colts were premedicated with acepromazine and anaesthesia was induced with detomidine and ketamine. Ponies were randomly allocated to receive halothane (HAL) or infusion of detomidine, ketamine and guaiphenesin (DKG) to maintain anaesthesia. Heart and respiratory rate, ECG, mean arterial blood pressure (MABP), cardiac index (CI), blood gases and plasma cortisol, ketamine and guaiphenesin were measured. Surgical castration took place between 45 and 75 min and anaesthesia lasted 90 min. MABP with DKG was significantly higher than with HAL, and, with HAL, MABP increased from pre-surgery (64 +/- 6 mmHg) to mid-surgery (80 +/- 5 mmHg) but did not change with DKG. At 30 min, CI was similar in both groups (57 +/- 7 ml/kg bwt/min); it decreased during surgery with HAL and remained low, but it increased slightly with DKG, and was higher than with HAL at 60 and 90 min. Plasma cortisol decreased in both groups until 40 min then increased with HAL only during surgery. Ketamine concentration reached a plateau (1.3-1.8 microg/ml) between 20 and 90 min and guaiphenesin concentration between 60 and 90 min (99-101 microg/ml). Recovery was generally smooth in both groups. This study demonstrated that during HAL the increase in blood pressure associated with surgical stimulus is accompanied by decreased CI; this did not occur during DKG which is likely to lead to better tissue perfusion than HAL. The adrenocortical activity seen during HAL was absent during DKG which may result from pituitary depression, analgesic effects of total intravenous anaesthesia (TIVA) or better perfusion.

Anesthesia, Intravenous↗

Isolation of cholesterol oxidation products from animal fat using aminopropyl solid-phase extraction.

Cholesterol oxidation products were separated from triglycerides and cholesterol in a single step on an aminopropyl solid-phase extraction column. The products were purified by subsequent transesterification and saponification, derivatized to trimethylsilyl ethers and analyzed by gas chromatography. Heated cholesterol-containing fat samples were autoxidized by bubbling air through them. When the flow-rate of air was set at 100 ml/min, the concentration of cholesterol oxidation products in the fat increased to a maximum after 1-2 h and then decreased to almost a zero level after 8 h. The concentration of cholesterol oxidation products in the fat increased over a similar time period, without reaching a maximum, when the flow-rate of air was decreased to 5 ml/min.

Adipose Tissue↗

Intra-articular morphine and saline injections induce release of large molecular weight proteoglycans into equine synovial fluid.

Both morphine and physiologic saline injected intra-articularly into healthy equine tarsocrural joints induced a release of large molecular size proteoglycan (PG) subunits into the synovial fluid (SF) analysed 24 h postinjection. High-performance liquid chromatography (HPLC) with a size-exclusion column was used to assess the high molecular weight proteoglycans in equine synovial fluid (SF). The PG peaks of SF samples eluated separately from SF hyaluronate and other molecular components of the SF in the HPLC chromatographies indicating no interaction between hyaluronate and PG in the SF. Individual elution profiles varied between joints and horses. The amount of PG release was measured by relative area index from the HPLC chromatograms. The synovial fluid PG content was significantly increased (P < 0.05) after morphine but not in saline injected joints compared with pretreatment but there were no significant differences between the two groups. It was concluded that intra-articular injections of both morphine and physiologic saline are able to elicit a marked PG release into the SF from articular cartilage within 24 h of injection.

Animals↗

Evaluation of a modification of the Hudson demand valve in ventilated and spontaneously breathing horses.

Hypoxaemia commonly develops during general anaesthesia and in the recovery period in horses. The Hudson demand valve has been used to increase arterial PO2, but it has been found to increase airway resistance considerably when used during spontaneous ventilation. This paper evaluates a modification of the valve designed to reduce this resistance. The effects of the valve and its modification on arterial oxygen (PaO2), and carbon dioxide (PaCO2) tensions were evaluated in four ponies anaesthetised by a total intravenous technique. The valve increased PaO2 from 8.3 +/- 1.1 to 32.7 +/- 7.6 kPa during spontaneous ventilation and to 44.2 +/- 7.4 kPa during intermittent positive pressure ventilation. With the modification, the PaCO2 was increased to 9.0 +/- 2.5 kPa during spontaneous ventilation PaO2 was unchanged by the valve (7.2 +/- 0.4 kPa to 7.1 +/- 0.7 kPa) but it was reduced to 6.4 +/- 0.9 kPa with the modification. The valve was also evaluated in 20 clinical cases during their recovery from halothane anaesthesia. It increased PaO2 from 7.4 +/- 2.1 kPa to 17 +/- 18.3 kPa during spontaneous ventilation and from 8.0 +/- 1.8 kPa to 23.4 +/- 22.2 kPa during positive pressure ventilation. With the modification, PaO2 was increased from 7.8 +/- 1.4 kPa to 10.4 +/- 3.8 kPa during spontaneous ventilation and from 7.6 +/- 1.5 kPa to 14.8 +/- 8.4 kPa during positive pressure ventilation. During spontaneous ventilation PaCO2 was increased from 5.9 +/- 0.4 kPa to 6.2 +/- 0.6 kPa with the unmodified valve and from 6.3 +/- 0.5 kPa to 6.6 +/- 0.5 kPa with the modification.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗

Analysis of the frequency spectrum of the equine electroencephalogram during halothane anaesthesia.

The electroencephalogram (EEG) has been used in human clinical anaesthesia as an indicator of cortical activity and as an indicator of the depth of anaesthesia. It would be useful if it provided a reliable indication of the depth of anaesthesia of horses. In this study anaesthesia was induced with thiopentone and maintained with halothane in nine ponies. The end tidal halothane concentration (PE-Hal) was monitored and 20 seconds of EEG were recorded at 0.8 per cent, 1.0 per cent and 1.2 per cent halothane, equivalent to the minimum alveolar concentration (MAC), 1.25 MAC and 1.5 MAC. Each 20 second block of data was divided into one second segments and averaged to give one second of averaged EEG from which a frequency spectrum was obtained by using a fast Fourier transformation. The power of the waveform at low frequency (1 to 3 Hz) was compared with that at higher frequency (9 to 11 Hz). The median frequency and 95th percentile (spectral edge) were also calculated. The spectral edge frequency had the best correlation with PE-Hal.

Anesthesia, General↗

Early adoption of cyclosporine and recombinant human erythropoietin: clinical, economic, and policy issues with emergence of high-cost drugs.

The discovery of new drugs and their introduction into US markets will become an intense area of focus should health care reform result in Medicare insurance coverage for prescription drugs. Particular attention will be focused on high-cost drugs. Two high-cost drugs, cyclosporine and recombinant human erythropoietin (rHuEPO), introduced into the clinical management of patients with kidney disease during the past decade, provide some experience concerning the forces affecting the use of expensive drugs in a cost-conscious health care system. The decision to prescribe a drug will depend on provider's judgements of the drug's clinical benefits and costs compared with those of other possible therapies. It may also depend on payment policy. Both cyclosporine and rHuEPO were adopted rapidly and extensively by providers of end-stage renal disease care following US Food and Drug Administration approval, despite their high costs. Both drugs were remarkably effective, relatively safe, and able to be administered without great difficulty compared with the therapies they have replaced. There was no additional payment to hospitals for the initial use of cyclosporine, which was introduced in 1983 at the time when Medicare's prospective payment was established, since choice of immunosuppressive agent did not affect the fixed, per-admission payment determined by the diagnosis-related group for kidney transplantation. Medicare coverage for continuing outpatient use of cyclosporine was not initially provided, in contrast to rHuEPO, which was introduced in 1989 with Medicare outpatient coverage and payment of 80% of the allowed charge. Despite their high costs and different methods of insurance payment both drugs achieved a rather quick and high penetration rate into their respective populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclosporine↗

Postoperative analgesia using phenylbutazone, flunixin or carprofen in horses.

Horses undergoing surgery were randomly assigned to one of three groups to receive phenylbutazone at 4 mg/kg (n = 72), flunixin at 1 mg/kg (n = 68) or carprofen at 0.7 mg/kg (n = 63) by slow intravenous injection at the end of surgery, just before they were disconnected from halothane. Pain was assessed by either of two resident surgical clinicians (who did not know which non-steroidal anti-inflammatory drug had been given) when the horses first stood up, two and four hours later and the next morning. If repeated doses of analgesic drugs were given the time was recorded and taken as an end point for the study. The presence or absence of side effects was also recorded. In the three groups there was no significant difference between the types of surgery performed, the numbers of horses requiring further analgesia or the pain scores at any time. In the horses needing further analgesia there was a significant difference in the time after surgery at which the further analgesia was given between those in the flunixin group, 12.8 +/- 4.3 hours (mean +/- sd) and those in the phenylbutazone group, 8.4 +/- 4.6 hours; the carprofen group had an intermediate interval of 11.7 +/- 6.9 hours. Significantly fewer of the horses that received butorphanol during surgery needed further analgesia than of those that did not receive any opioid.

Analgesia↗