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Biomedical subjects

R Payne

Publications and source records attributed to R Payne.

At least 19 recordsLinked to original sources
PubMed2000

Chronic pain: challenges in the assessment and management of cancer pain.

Assessing and managing pain while caring for the whole patient is a challenge for physicians. Barriers to pain management include clinician-, patient-, and health system-related issues. The traditional model of care is focused on disease-specific treatments. If these treatments fail, the focus shifts to palliation. A new model of care integrates disease-specific treatments with palliative care and rehabilitation. This model includes prevention and treatment of suffering. An essential element of this model is evaluation of the patient's concerns about the future and fear. Treating patient pain with quality pain management and palliative care involves a holistic pain assessment and management strategy.

Chronic Disease↗
PubMed1999

Protein kinase C activators inhibit the visual cascade in Limulus ventral photoreceptors at an early stage.

The phosphoinositide cascade mediates visual transduction in invertebrate photoreceptors. Phospholipase C (PLC) catalyzes the hydrolysis of phosphatidylinositol bisphosphate, producing inositol trisphosphate (InsP(3)) and diacylglycerol (DAG). Protein kinase C (PKC) is a major target of DAG in many cell types. We have used PKC activators to investigate the function of the kinase in the phototransduction cascade in Limulus polyphemus ventral photoreceptors. Extracellular application of (-)-indolactam V (0. 03-30 microM) or phorbol-12,13-dibutyrate (10 microM) reversibly reduced the sensitivity of the electrical response of the photoreceptors to light by up to 1000-fold. The inert stereoisomer (+)-indolactam V and 4alpha-phorbol had no effect. The effect of (-)-indolactam V was antagonized by the PKC inhibitors bisindolylmaleimide I and Gö 6976. Coapplication of bisindolylmaleimide V, used as a negative control compound for PKC inhibition, did not reduce the effectiveness of (-)-indolactam V. These findings are consistent with (-)-indolactam V activating PKC and desensitizing the light response. Furthermore, our pharmacological results indicate that PKC activation does not appear to play a role in light adaptation. We localized the position of the target of PKC in the visual cascade. We chemically excited the cascade at various stages to determine the kinase's target. PKC activation by (-)-indolactam V decreased the light-induced elevation of intracellular calcium but had no effect on the photoreceptor's excitatory response to intracellular injection of InsP(3). However, the PKC activator greatly reduced the excitation caused by GTP-gamma-S injection. We propose that PKC inhibits the visual transduction cascade at the G-protein and/or PLC stage.

Adaptation, Ocular↗
PubMed1999

Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in cancer patients: a controlled dose titration study.

Oral transmucosal fentanyl citrate (OTFC) is a novel opioid formulation in which the potent synthetic mu-agonist fentanyl is embedded in a sweetened matrix that is dissolved in the mouth. It is undergoing investigation as a treatment for cancer-related breakthrough pain, a prevalent phenomenon defined as a transitory flare of moderate to severe pain that interrupts otherwise controlled persistent pain. There have been no controlled trials of other treatments for this condition. To evaluate the safety and efficacy of ascending doses of OTFC, a novel controlled dose titration methodology was developed that applied blinding and randomization procedures to the evaluation of recurrent pains in the home environment. The study was a multicenter, randomized, double-blind dose titration study in ambulatory cancer patients. The sample comprised adult patients receiving a scheduled oral opioid regimen equivalent to 60-1000 mg oral morphine per day, who were experiencing at least one episode per day of breakthrough pain and had achieved at least partial relief of this pain by use of an oral opioid rescue dose. After collection of 2 days of baseline data concerning the efficacy of the usual rescue drug, patients were randomly treated with either 200 or 400 microg OTFC unit doses in double-blind fashion. Up to two breakthrough pains each day could be treated with up to four OTFC unit doses per pain. OTFC in unit doses containing 200, 400, 600, 800, 1200 or 1600 microg of fentanyl citrate were available for the study. The unit dose was titrated upward in steps until the patient had 2 consecutive days on which breakthrough pain could be treated with the single unit dose, titration was ineffective at a 1600 microg unit dose, or 20 days elapsed. To maintain the double-blind, orders to titrate up were ignored one-third of the time according to a pre-defined randomization schedule accessible only to an unblinded study pharmacist. Main outcome measures included, numeric or categorical measures of pain intensity, pain relief, and global assessment of drug performance. Dose response relationships were found suggesting that the methodology was sensitive to opioid effects. Seventy-four percent of patients were successfully titrated. There was no relationship between the total daily dose of the fixed schedule opioid regimen and the dose of OTFC required to manage the breakthrough pain. Although the study was not designed to provide a definitive comparison between OTFC and the usual rescue drug, exploratory analyses found that OTFC provided significantly greater analgesic effect at 15, 30 and 60 min, and a more rapid onset of effect, than the usual rescue drug. Adverse effects of the OTFC were typically opioid-related, specifically somnolence, nausea and dizziness. Very few adverse events were severe or serious. This study demonstrated the feasibility of controlled trial methodology in studies of breakthrough pain. OTFC appears to be a safe and effective therapy for breakthrough pain, and dose titration can usually identify a unit dose capable of providing adequate analgesia. If the lack of a relationship between the effective OTFC dose and fixed schedule opioid regimen is confirmed, dose titration may be needed in the clinical use of this formulation. Further investigation of OTFC as a specific treatment for breakthrough pain is warranted.

Administration, Oral↗
PubMed1999

Molecular cloning of a putative cyclic nucleotide-gated ion channel cDNA from Limulus polyphemus.

Cyclic nucleotide-gated channels have been proposed to mediate the electrical response to light in the ventral photoreceptor cells of the horseshoe crab, Limulus polyphemus. However, a cyclic nucleotide-gated channel has not been identified from Limulus. We have cloned a putative full-length cyclic nucleotide-gated channel cDNA by screening cDNA libraries constructed from Limulus brain using a probe developed from Limulus ventral eye nerves. The putative full-length cDNA was derived from two overlapping partial cDNA clones. The open reading frame encodes 905 amino acids; the sequence shows 44% identity to that of the alpha subunit of the bovine rod cyclic GMP-gated channel over the region containing the transmembrane domains and the cyclic nucleotide binding domain. This Limulus channel has a novel C-terminal region of approximately 200 amino acids, containing three putative Src homology domain 3 binding motifs and a putative coiled-coil domain. The possibility that this cloned channel is the same as that detected previously in excised patches from the photoreceptive membrane of Limulus ventral photoreceptors is discussed in terms of its sequence and its expression in the ventral eye nerves.

Animals↗
PubMed1998

Light-induced Mn2+ influx in Limulus ventral photoreceptors.

In contrast to insect species, light-activated influx of divalent ions into Limulus ventral photoreceptors has proven difficult to demonstrate. We used the quench of the fluorescent indicator dye, fura-2, to measure Mn2+ influx. Limulus ventral photoreceptors were injected with fura-2 and excited at 360 nm. When the photoreceptors were bathed in 1 mmol.l-1 Mn2+, an approximately 1% per 10 s decline in the fura-2 fluorescence during intervals between 50-ms flashes was taken as a measure of Mn2+ entry in darkness. Fluorescence decline during 10-s flashes was used to monitor Mn2+ entry during the photoresponse. During the 10-s flashes we observed a small rapid decline of the fura-2 fluorescence even in the absence of Mn2+. This reflected a contamination of the fluorescence signal arising from light-induced release of intracellular calcium stores. A subsequent slower decline in fluorescence during the 10-s flash, amounting to approximately 9% per 10 s, was only observed in the presence of extracellular Mn2+ and was attributed to Mn2+ influx. This light-activated influx was not through voltage-gated calcium channels since it persisted under voltage clamp, was not stimulated by depolarizing current injections, nor blocked by NiCl2. Depletion of internal calcium stores by cyclopiazonic acid treatment did not accelerate Mn2+ influx.

Animals↗
PubMed1998

Putative inositol 1,4,5-trisphosphate receptor localized to endoplasmic reticulum in Limulus photoreceptors.

Invertebrate microvillar photoreceptors utilize the phosphoinositide cascade to transduce light stimuli and inositol 1,4,5-trisphosphate is thought to be one of the messengers that triggers the electrical response by mobilizing intracellular stored calcium. To further characterize the role of the phosphoinositide signaling pathway in invertebrate phototransduction, we have examined the distribution of inositol 1,4,5-trisphosphate receptors in Limulus lateral eye and ventral nerve photoreceptors using an immunohistochemical approach combined with confocal microphotolysis of caged inositol 1,4,5-trisphosphate. We have localized the inositol 1,4,5-trisphosphate receptor using an antibody raised against a highly conserved region of the N-terminal of the protein. In lateral eye photoreceptors, the antibody intensely stains cytoplasm directly beneath the photoreceptive microvilli, containing subrhabdomeral cisternae of endoplasmic reticulum. In ventral nerve photoreceptors, the distribution of immunostaining was more homogeneous than within the lateral eye photoreceptors. Simultaneous confocal microphotolysis of caged inositol 1,4,5-trisphosphate and Ca2+ measurements using the fluorescent indicator Calcium Green 5N were performed to estimate inositol 1,4,5-trisphosphate-induced Ca2+ release in functionally distinct areas of the ventral nerve photoreceptors. This is the first direct demonstration of the localization of putative inositol 1,4,5-trisphosphate receptor in invertebrate visual cells. The inositol 1,4,5-trisphosphate receptor appears to be localized predominantly to endoplasmic reticulum and taken in conjunction with earlier physiological data from other workers, our result supports a central role for the phosphoinositide pathway in visual transduction in Limulus photoreceptors.

Animals↗
PubMed1998

Presenting symptoms in patients referred to a multidisciplinary clinic for bone metastases.

Symptom control is the goal of palliative irradiation. Approximately 1 month is required before symptomatic relief is accomplished with radiotherapy. However, many patients with cancer-related pain do not receive adequate analgesics, and opioids are often not prescribed until patients fail to respond to palliative irradiation. The presenting symptoms of 108 patients who were referred to a multidisciplinary clinic for bone metastases were evaluated with the Wisconsin Brief Pain Inventory (BPI). This validated instrument evaluates the severity of pain using a 0-10 scale; 10 represents the worst pain imaginable. The population comprised 65 men (60%) and 43 women whose ages ranged from 33 years to 81 years; median age was 55 years, and 69% of patients were less than 65 years of age. Despite the presence of metastatic disease, 21% of patients were working full-time outside the home, and 6% were employed part-time outside the home; 13% were homemakers. Only 17 patients (16%) were unemployed. The time since diagnosis ranged from 2 weeks to 23 years; the median time since diagnosis was 22 months, and 30% of patients had been diagnosed with the past 6 months. Pain was a presenting symptom in 74% (N = 80) of patients at diagnosis. At its worst, the pain was rated as severe (levels 7-10) by 78% and intolerable (level 10) in 22% of the patients in the 24 hr prior to the clinic appointment. On average, the pain was rated moderate to severe (levels 4-10) in 79% and severe in 23% of patients. Only 45% of patients experienced good relief from the prescribed analgesics, and 23% of patients indicated that the prescribed analgesics were ineffective. This survey demonstrates that bone metastases incur significant pain that is often undertreated with analgesics before antineoplastic therapy is administered.

Adult↗
PubMed1998

Radiotherapy residents' knowledge of and attitudes toward management of cancer pain.

PURPOSE: To evaluate the fund of knowledge of and attitudes toward cancer pain management of radiotherapy residents across the nation. METHODS: Radiotherapy (XRT) residents who had completed at least a year of training were surveyed by questionnaire. Residents (n = 10) from a training program who had been given instructional resources in cancer pain management skills were compared with residents from across the nation (n = 61). A validated survey used in national Cancer Pain Initiative Role Model Programs was administered by mail. The survey contained 30 questions that evaluated attitude alone (A), knowledge alone (K), and how attitude affects the application of knowledge (A/K). RESULTS: The residents from the training program scored significantly higher in K (p < 0.005) and A/K (p < 0.04) than did the residents across the nation. No difference in scores evaluating A were detected (p = 0.26). Compared with the baseline knowledge of physicians in practice who had attended a workshop on cancer pain management, the national XRT residents had significantly lower scores in A (p < 0.006) and K (p < 0.001); however, no difference was found in A/K scores. After the workshop, the physicians in practice had significant gains in cancer pain management skills (p < 0.006). When the post-instruction survey was compared with the national XRT resident scores, there were marked differences in A (p < 0.00001), K (p < 0.00001) and A/K (p < 0.01). CONCLUSIONS: XRT residents in the United States are empathetic, but knowledge of cancer pain management is lacking. Instruction in the principles of cancer pain management can make a profound difference in knowledge and attitude. There is a need to recognize cancer pain management as a significant aspect of radiotherapeutic practice.

Attitude of Health Personnel↗
PubMed1998

Quality of life and cancer pain: satisfaction and side effects with transdermal fentanyl versus oral morphine.

PURPOSE: To compare pain-related treatment satisfaction, patient-perceived side effects, functioning, and well-being in patients with advanced cancer who were receiving either transdermal fentanyl (Duragesic, Janssen Pharmaceuticals, Titusville, NJ) or sustained-release oral forms of morphine (MS Contin, Perdue Frederick Co, Norwalk, CT, or Oramorph SR, Roxanne Laboratories, Columbus, OH). PATIENTS AND METHODS: A total of 504 assessable cancer patients participated in this cross-sectional, quality-of-life study. Relevant elements of four validated scales were used--the Functional Assessment of Cancer Therapy-General (FACT-G) scale, the Brief Pain Inventory (BPI), the Medical Outcomes Study (MOS) questionnaire, and the Memorial Symptom Assessment Scale (MSAS)--as well as original scales that were developed and validated for this study. RESULTS: The majority of patients in both treatment groups had late-stage (IV/D) cancer. Patients who received transdermal fentanyl were more satisfied overall with their pain medication than those who received sustained-release oral forms of morphine (P = .035). Fentanyl patients also experienced a significantly lower frequency (P < .002) and impact (P < .001) of pain medication side effects. These results occurred despite the fact that cancer patients who received fentanyl were significantly older (P < .001) and had significantly lower functioning and well-being scores (P = .001). Measures of pain intensity, sleep adequacy, and symptoms demonstrated no significant differences between treatment groups. CONCLUSION: These data suggest that patients are more satisfied with transdermal fentanyl compared with sustained-release oral forms of morphine. A lower frequency and reduced impact of side effects with transdermal fentanyl may be one reason cancer patients who receive fentanyl are more satisfied with their pain management.

Administration, Cutaneous↗
PubMed1998

Practice guidelines for cancer pain therapy. Issues pertinent to the revision of national guidelines.

The high prevalence of pain in cancer patients has been appreciated for a long time. However, despite release of cancer pain management guidelines by the Agency for Health Care Policy and Research (AHCPR) in 1994, pain is still undertreated. Recent reports in the literature have identified multiple factors that influence analgesic response and pain management, such as the ethnicity, gender, and age of the patient. Recognition of these factors, and the availability of new drugs, alternative delivery methods, and an enhanced understanding of pain mechanisms and receptor pharmacology compel a revision of the existing cancer pain management guidelines. Assessment and management of pain and other symptoms in cancer patients that influence the quality of survival are increasingly being incorporated into randomized-controlled clinical trials. Strategies should be developed by the National Comprehensive Cancer Network (NCCN) to develop and implement extant and revised pain management guidelines into clinical practice and test new hypotheses regarding pain management treatments in clinical trials.

Analgesics↗
PubMed1998

Factors influencing quality of life in cancer patients: the role of transdermal fentanyl in the management of pain.

A transdermal fentanyl patch for the treatment of chronic cancer-related pain is available in four dosages (25, 50, 75, and 100 microg/hr). Fentanyl is released from a 72-hour reservoir by diffusion through a controlled-release membrane to the skin, through which it is absorbed into the microcirculation. The pharmacokinetics of fentanyl differ markedly as a function of the route of administration. Unlike intravenous administration, in which peak plasma levels occur within minutes and the plasma elimination half-life is 2 to 3 hours, after initial transdermal fentanyl patch application, peak levels occur within 14 hours and the elimination half-life exceeds 24 hours. When compared with oral morphine at doses effecting the same degree of pain relief, fewer gastrointestinal disturbances (nausea, vomiting, and constipation) and better alertness and sleep quality have been reported in two studies. The transdermal fentanyl patch is as effective as oral opioids in relieving cancer-related pain, with a safety and side effect profile equal to or better than that of oral opioids. The convenient, once-every-72 hours dosing regimen is easily adjusted to the individual's need for around-the-clock pain control, and provides stable and predictable therapeutic drug plasma concentrations. Patient acceptability is high and the cost is lower than other methods required to deliver parenteral opioids. The recent development of an oral transmucosal fentanyl citrate delivery system for the treatment of breakthrough pain will further expand the use of transdermal fentanyl patches for the treatment of chronic pain.

Administration, Cutaneous↗
PubMed1997

Growth cone interactions with purified cell and substrate adhesion molecules visualized by interference reflection microscopy.

The migration of growth cones on substrates consisting of naturally occurring cell adhesion molecules has been extensively studied in cell culture. However, relatively little is known about how growth cones contact the substrate or how the patterns of contact change as growth cones move forward. We have examined the interactions of chick retinal ganglion cell growth cones with laminin, merosin, N-cadherin, L1 and poly-L-lysine by time-lapse interference reflection microscopy (IRM) using a laser scanning confocal microscope. In images obtained by IRM, areas of a cell that are closely apposed to the substrate appear dark whereas areas that are farther away appear light. Growth cones on Jaminin and merosin were almost uniformly light, indicating that very little of the membrane was in close contact with the substrate. Growth cones on N-cadherin had a mottled appearance with some relatively large dark gray areas. The proximal portions of filopodia often were dark, in contrast to those on laminin and merosin which were light. In addition, growth cones on N-cadherin had numerous dark gray punctate regions of close association with the substrate. Growth cones on L1 had darker regions than growth cones on other substrates and these comprised a larger fraction of their area. There also were differences in the temporal dynamics of growth cone interactions with different substrates and these differences correlated with differences in rates of growth. None of the contacts observed in growth cones were as dark or stable as focal contacts of fibroblasts.

Animals↗
PubMed1997

Rapid coupling of calcium release to depolarization in Limulus polyphemus ventral photoreceptors as revealed by microphotolysis and confocal microscopy.

Microphotolysis and confocal microscopy were used to investigate the timing of calcium release and of the electrical response in Limulus polyphemus ventral photoreceptors. The fluorescent dyes Fluo-3 and Calcium Green-5N were used to monitor local Ca2+ elevations. Photolysis of caged inositol trisphosphate (InsP3) close to the plasma membrane of the light-sensitive rhabdomeral (R-) lobe resulted in Ca2+ elevation within 10-20 msec, 20-45 msec before the physiological response to light normally would be detected. Inward ionic current flow and depolarization followed InsP3-induced calcium release within 2.5 +/- 3.3 msec. Voltage-clamping the cells and removal of extracellular Ca2+ did not affect the timing of the Ca2+ elevation that followed the photolysis of caged InsP3 or its relationship to the electrical response. In contrast to the physiological response to light, which only released calcium within the R-lobe, photolysis of InsP3 elevated Cai in both lobes, although with much greater effect in the R-lobe, as compared with the bulk of the A-lobe, suggesting the presence of InsP3-sensitive calcium stores in both lobes. Photolysis of caged calcium [o-nitrophenyl EGTA (NPE)] at the edge of the R-lobe activated an inward ionic current within 1.8 +/- 0.7 msec. This NPE-induced current reversed at a membrane potential of 10 +/- 6 mV in the range typical of that of the light-activated current under physiological conditions. Calcium release, therefore, activates an inward current rapidly enough to contribute to the electrical response to light.

Action Potentials↗