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Biomedical subjects

R Payne

Publications and source records attributed to R Payne.

At least 127 records · Page 7Linked to original sources

Role of epidural and intrathecal narcotics and peptides in the management of cancer pain.

The spinal administration of opioids may provide analgesia of long duration to patients with bilateral or midline lower abdominal or pelvic cancer pain. However, cross-tolerance to orally and parenterally administered narcotics and the rapid development of tolerance to spinal narcotics have limited their usefulness. Opioids have extensive distribution in the CSF and plasma when administered into the epidural or intrathecal space, and delivery of drug to brain stem sites may account for many of the toxic and therapeutic effects of spinal opioids. Further clinical and pharmacokinetic studies are required to provide the information regarding: the optimal opioids for use as spinal analgesics; equieffective dose ratios of spinal opioids in comparison to parenteral or oral opioids; strategies useful to forestall the development of tolerance of spinally administered opioids; the analgesic efficacy of this therapy in opioid-tolerant patients; and the role of spinally administered nonopioid analgesics in the management of cancer pain in the tolerant patient. These questions will need resolution before this therapy can be recommended for routine use in the management of cancer pain.

Analgesia↗

Inositol 1,4,5 trisphosphate releases calcium from specialized sites within Limulus photoreceptors.

We have investigated the subcellular distribution and identity of inositol trisphosphate (InsP3)-sensitive calcium stores in living Limulus ventral photoreceptor cells, where light and InsP3 are known to raise intracellular calcium. We injected ventral photoreceptor cells with the photoprotein aequorin and viewed its luminescence with an image intensifier. InsP3 only elicited detectable aequorin luminescence when injected into the light-sensitive rhabdomeral (R)-lobe where aequorin luminescence induced by light was also confined. Calcium stores released by light and InsP3 are therefore localized to the R-lobe. Within the R-lobe, InsP3-induced aequorin luminescence was further confined around the injection site, due to rapid dilution and/or degradation of injected InsP3. Prominent cisternae of smooth endoplasmic reticulum are uniquely localized within the cell beneath the microvillar surface of the R-lobe (Calman, B., and S. Chamberlain, 1982, J. Gen. Physiol., 80:839-862). These cisternae are the probable site of InsP3 action.

Aequorin↗

CSF distribution of opioids in animals and man.

The CSF distribution of opioids after subarachnoid administration is important in determining therapeutic and undesirable side-effects. There are many factors which influence CSF distribution of opioids including the age, position, anatomy of the spinal column of the patient or animal, and the physico-chemical properties of the opioid solution and of the CSF. Opioids are cleared from their site of administration in CSF by three mechanisms: 1) uptake into the spinal cord, 2) diffusion through the dura and uptake into the blood, and 3) rostral-caudal CSF distribution. Physico-chemical factors such as lipid solubility, degree of ionization in the CSF and the baricity of the opioid solution are important in determining the rate of clearance by these three routes. Opioids which are highly lipid soluble, have high affinity for delta and/or kappa opiate receptor subtypes, and are largely non-ionized at physiologic CSF pH, would have optimal pharmacokinetic properties for subarachnoid administration. These properties would allow administration of a small dose of opioid which would be rapidly taken up into the spinal cord, thereby limiting CSF and vascular distribution to supraspinal brain regions.

Analgesia↗

Novel routes of opioid administration in the management of cancer pain.

Administration of opioids by less conventional routes may produce pain relief of more rapid onset, of longer duration, and fewer side effects in comparison with conventional oral or parenteral administration. This review will discuss the indications, efficacy, complications and potential advantages of these novel routes of administration.

Analgesia, Epidural↗

Neck pain in the elderly: a management review. Part I.

Degenerative disease of the cervical spine is a common cause of neck pain in the elderly. This article reviews the pathogenesis, clinical features, and management of cervical spondylitic radiculopathy and myelopathy in the elderly.

Aged↗

Neck pain in the elderly: a management review. Part II.

Rheumatoid arthritis and metastatic cancer occur commonly in the elderly, and may cause neck pain. Rheumatoid arthritis may produce cervical radiculopathy and myelopathy resulting from vertebral body subluxation, although radiological manifestations of subluxation are much more common than neurological dysfunction. Cervical spinal cord compression is a neurological emergency and may produce cervical radiculopathy as well as myelopathy. Careful neurological and radiological assessments are required to minimize pain and preserve neurological function in elderly patients suffering from neck pain complicating rheumatoid arthritis or cervical spinal metastasis.

Aged↗

Paraneoplastic opsoclonus-myoclonus. Association with medullary thyroid carcinoma and review of the literature.

The syndrome of opsoclonus-myoclonus (OM) is an infrequent but well-known "remote effect" of neuroblastoma in children. The OM syndrome is even less frequent in adults. A few cases of adult paraneoplastic OM have been described in association with several systemic neoplasms. We report the unique case of a 29-year-old man with metastatic medullary thyroid carcinoma in whom OM developed as part of a generalized transient encephalopathy. We outline the postulated anatomic lesions and pathophysiologic mechanisms underlying the OM syndrome, as well as examine the possible connections between the neuroendocrine derivation of medullary thyroid carcinoma and the neurotoxic and/or autoimmune theories of the causation of the OM syndrome in patients with systemic neoplasms.

Adult↗

A chronic sheep preparation for the study of drug pharmacokinetics in spinal and ventricular CSF.

We describe a sheep preparation utilizing chronic vascular and subarachnoid catheterization and ventriculocisternal perfusion. This preparation allows simultaneous, atraumatic sampling of plasma and CSF after drug administration by the intravenous, intracerebroventricular, or lumbar intrathecal (i.t.) routes in an unanesthesized animal. This sheep preparation provides a convenient means of studying the CSF distribution of exogenous and/or endogenous substances. During intravenous infusion at a rate of 2.2 micrograms/kg/min, morphine appears in cisternal CSF within 15 min. The steady-state plasma concentration and CSF flux (or appearance rate) of morphine was 0.037 and 0.009 micrograms/min, respectively. At steady state, 0.008% of the administered dose appears in CSF/min. The coadministration of morphine, methadone, and [14C]sucrose into the fifth lumbar subarachnoid space is associated with the simultaneous appearance of morphine and [14C]sucrose, but not methadone, in cisternal CSF. The ratio of [14C]sucrose to morphine increased by nearly sevenfold in cisternal CSF, indicating clearance of morphine relative to [14C]sucrose as the compounds ascend in the CSF axis. The simultaneous appearance of morphine and [14C]sucrose in cisternal CSF after lumbar subarachnoid administration indicates that morphine, like sucrose, is distributed within the CSF by bulk flow. This sheep preparation can be used to provide the quantitative data necessary for the development of pharmacokinetic-pharmacodynamic models that relate plasma and CSF concentrations of opiates to their pharmacological effects. These studies will help to provide the pharmacological rationale for the administration of opiates by novel routes for pain management in man.

Animals↗

Localization of the photocurrent of Limulus ventral photoreceptors using a vibrating probe.

We have used a vibrating probe to determine the profile of electrical current density around ventral photoreceptors of the horseshoe crab following flashes of light that uniformly illuminated the entire surface of the photoreceptor's cell body. The vibrating probe signal indicated that the density of inward current was greatest at the distal region of the cell, the region that is expected to contain the light-sensitive rhabdom. The density of inward current typically declined at the midpoint of the cell body and then reversed to an outward current flow in the proximal region of the cell body, close to the axon. The profile of local sensitivity of the photoreceptor to light closely matched the profile of inward current density, suggesting that the light-activated conductance is localized to the light-sensitive region of the cell.

Animals↗

The initial response of Limulus ventral photoreceptors to bright flashes. Released calcium as a synergist to excitation.

The leading edge of the response of Limulus ventral photoreceptors to brief flashes was investigated using a voltage clamp. The leading edge of responses increases linearly with flash intensity when dim flashes produce less than one photoisomerization per square micron of cell surface. Brighter flashes accelerate the initial portion of the response, resulting in a fourth-power relationship between the magnitude of the response at brief times after the flash and the flash intensity. The onset of this nonlinearity with increasing flash intensity is determined by the local density of photoisomerizations within the receptor. Responses to bright 10-15-mum-diam spots therefore rise faster than responses to diffuse flashes producing the same number of photoisomerizations within the receptor. Background illumination shortens the response latency and suppresses the initial nonlinearity. These phenomena can be explained by a model of transduction in which light activates two parallel cascades of reactions. Particles released by the first of these cascades open ionic channels, while the second produces an agent that accelerates the rate of production of particles by the first. Injection of the calcium buffer EGTA slows the initial portion of the response to bright flashes and suppresses its nonlinearity, which suggests that the accelerating agent released by the second cascade is calcium.

Animals↗

Pressure injection of calcium both excites and adapts Limulus ventral photoreceptors.

Single pressure injections of 1-2 mM calcium aspartate into the light-sensitive region of Limulus ventral photoreceptors resulted in a rapid, 20-40-mV depolarization lasting approximately 2 s. The depolarization closely followed the rise in intracellular free calcium caused by the injection, as indicated by aequorin luminescence. The depolarization was followed by reversible desensitization (adaptation) of responses to both light and inositol 1,4,5 trisphosphate. Similar single injections of calcium into the light-insensitive region of the receptor were essentially without effect, even though aequorin luminescence indicated a large, rapid rise in intracellular free calcium. The depolarization caused by injection of calcium arose from the activation of an inward current with rectification characteristics and a reversal potential between +10 and +20 mV that were similar to those of the light-activated conductance, which suggests that the same channels were activated by light and by calcium. The reversal potentials of the light- and calcium-activated currents shifted similarly when three-fourths of the extracellular sodium was replaced by sucrose, but were not affected by a similar replacement of sodium by lithium. The current activated by calcium was abolished by prior injection of a calcium buffer solution containing EGTA. The responses of the same cells to brief light flashes were slowed and diminished in amplitude, but were not abolished after the injection of calcium buffer. Light adaptation and prior injection of calcium diminished the calcium-activated current much less than they diminished the light-activated current.

Adaptation, Physiological↗

Excitation and adaptation of Limulus ventral photoreceptors by inositol 1,4,5 triphosphate result from a rise in intracellular calcium.

Single pressure injections of 1-10 pl of inositol 1,4,5 triphosphate (IP3) or inositol 4,5 bisphosphate [I(4,5)P2] excite Limulus ventral photoreceptors by inducing rapid bursts of inward current. After excitation by IP3, responses to subsequent injections of IP3 or light flashes are often reversibly diminished (adapted). Single injections of IP3 and I(4,5)P2 are effective at concentrations in the injecting pipette of 20 microM to 1 mM. Single injections of inositol 1,4 bisphosphate are ineffective at concentrations of 100-500 microM. Excitation by IP3 or I(4,5)P2 is accompanied by a rise in intracellular free calcium, as indicated by aequorin luminescence. Prior injection of calcium buffer solutions containing 100 mM EGTA greatly diminishes the total charge transferred across the plasma membrane during excitation by IP3 or I(4,5)P2, which suggests that a rise in Cai is necessary for excitation by the inositol polyphosphates. Adaptation of the response to light by IP3 is also abolished by prior injection of EGTA. In the same cells, the response to brief light flashes is slowed and diminished in amplitude by the injection of calcium buffer, but the charge transferred during the response is not significantly diminished. This suggests that light has access to a pathway of excitation in the presence of EGTA that is not accessible to intracellularly injected IP3.

Adaptation, Physiological↗

Back pain in the elderly: updated diagnosis and management.

CT of compression fractures is a useful adjunct to the plain x-ray in excluding signs of metastasis. However, increased bone density on CT may not distinguish osteoporotic fractures from neoplastic disease, in which case radioiodine scan, bone and marrow biopsies, or myelography may be necessary. Surgery for painful osteoarthritic spinal disease is controversial. The potential advantages of surgery must be weighted against the risk of anesthesia, the length and tolerance of postoperative immobility, and the effect of laminectomy and fusion on the biomechanics of the spine. Furthermore, the elderly are at increased risk for postoperative complications.

Aged↗

CSF distribution of morphine, methadone and sucrose after intrathecal injection.

The lumbar to cisternal CSF distribution of morphine and methadone were compared to C-14 sucrose, a standard marker of CSF bulk flow, after lumbar subarachnoid injections in a sheep preparation. Morphine appeared and peaked simultaneously with C-14 sucrose in cisternal CSF at 90 to 190 minutes. The mean peak cisternal CSF morphine concentrations were sustained for 30-40 minutes, and averaged 148 ng/ml, representing 0.3% of the administered dose. Methadone was not detectable in cisternal CSF up to 240-300 minutes after lumbar subarachnoid administration. The C-14 sucrose/morphine ratio was increased an average of 6.7 times in cisternal CSF as compared to the ratio of the two compounds injected into the lumbar subarachnoid space. These studies demonstrate that morphine, a hydrophilic opioid, given intrathecally moves rostrally and appears in cisternal CSF by bulk flow. Furthermore the rostral redistribution of morphine is associated with the clearance of morphine from CSF. Methadone, a lipophilic opioid, appears to be completely cleared from CSF before it reaches the cisterna magna. These pharmacokinetic studies support a contribution of supraspinal sites to the analgesic and adverse effects produced by morphine given by spinal routes of administration. In contrast methadone appears to exert its effects predominantly at spinal sites.

Animals↗

The postnatal functional development of muscle stretch receptors in the rat.

The response to a 5-sec stretch of the triceps muscle was studied in dorsal root filaments L5 of 72 infant rats (1-19 days old) under urethane anesthesia. More than 50% of all units in 1-day-old rats responded by repetitive firing until the end of the 5-sec stretch (slowly adapting or SA receptors), while the rest ceased to fire earlier (relatively rapidly adapting or 1/2 SA receptors), or gave an "on" response only. The number of units exhibiting an SA response increased with age and attained 80% in 5-day-old rats. By the 10th day of life, almost 90% of endings behaved as SA receptors. During development, the maximal discharge frequencies at the peak of stretch increased markedly, and their values in 18-day-old rats were comparable to those in adult rats. The phasic component of the response to stretch, although less well defined in the younger animals, was already present even in 1-day-old rats. Adaptation of the static response during maintained stretch was relatively steep in all the age groups studied. The results indicate that, in the rat, large numbers of muscle stretch receptors are capable of responding to sustained stretch as SA receptors, even at an age when their morphological and ultrastructural maturation is not yet fully accomplished.

Adaptation, Physiological↗

Aetiology of pneumonia in children in Goroka Hospital, Papua New Guinea.

To determine the aetiology of pneumonia in 83 children admitted to Goroka Hospital, Papua New Guinea, lung aspirates and blood were cultured for bacteria. Haemophilus infuenzae, Streptococcus pneumoniae, or both, were isolated from 43 (52%) of the children, other bacteria from 8 (10%), and no bacteria from 32 (39%). Of the 32 strains of H influenzae tested, 18 (56%) were non-serotypable, 8 (25%) were serotypes other than type b, and only 6 (19%) were type b. Viruses were isolated from lung or nasopharyngeal aspirates from 18 (29%) of the 62 children for whom viral cultures were done. It seems that, although viruses may initiate infection, death from pneumonia in children in developing countries is often due to H influenzae, S pneumoniae, or both. Antibiotic therapy would prevent many of these deaths. There is an urgent need for vaccines, effective in children less than 6 months old, that protect against all strains of H influenzae, and S pneumoniae.

Biopsy, Needle↗