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Biomedical subjects

R Payne

Publications and source records attributed to R Payne.

At least 73 records · Page 4Linked to original sources
PubMed1997

High-dose epidural infusion of opioids for cancer pain: cost issues.

The safety and efficacy of intraspinal opioids as therapy for selected patients with cancer pain are well-established. The choice of the appropriate drug is influenced by many variables that are to date incompletely elucidated. The cost of therapy is an increasingly important component of decision-making. This report describes the management of a patient who achieved excellent pain control with the administration of epidural sufentanil and bupivacaine. Daily Average Wholesale Price for sufentanil was, however, $698. Until the data comparing the efficacy of different epidurally administered opioids in the treatment of cancer pain are available, we suggest that treatment with more costly opioids be reserved for patients for whom analgesia cannot be achieved after maximizing epidural morphine analgesia with aggressive side-effect management.

Adult↗
PubMed1997

Sickle cell-related pain: perceptions of medical practitioners.

Pain is the most common problem encountered by patients with sickle cell disease (SCD). We report the results of a survey sent to hematologists and emergency department (ED) physicians regarding their perceptions and practices concerning pain and its management. Hematologists and ED physicians differed considerably in their perceptions about the natural history of the pain, and about the percentage of patients who are addicted to analgesics. Fifty-three percent of the ED physicians and 23% of the hematologists thought that more than 20% of patients are addicted. These beliefs and perceptions about SCD-related pain and the prevalence of addiction must be addressed if clinical care is to be changed substantively.

Anemia, Sickle Cell↗
PubMed1997

Palliation of intractable cancer pain by MRI-guided cingulotomy.

CASE REPORT: Three cases of intractable pain arising from widespread metastatic cancer with poor response to opioids were treated with MRI-guided cingulotomy. RESULTS AND CONCLUSIONS: In most cases, MRI-guided cingulotomy was associated with significant pain relief and reduced opioid use. To provide insight into the role of MRI-guided cingulotomy in oncologic pain refractory to more conservative measures, the relative risks and benefits of cingulotomy are discussed, along with the course of one patient who experienced postoperative cognitive impairment. This report also describes the relevant neurosurgical and pharmacotherapeutic issues associated with management of pain in patients with widespread metastatic disease.

Adult↗
PubMed1996

Teaching cancer pain management: durability of educational effects of a role model program.

BACKGROUND: Inadequate management of cancer related pain has resulted primarily from attitudinal barriers and a lack of knowledge about clinical assessment, the administration of analgesics, and therapeutic interventions. METHODS: Fifty health-care providers (13 physicians, 21 nurses, and 16 pharmacists), working as a team, participated in a Role Model Program that presented principles of cancer pain management. A questionnaire that evaluated the fund of knowledge and attitudes regarding cancer pain management was administered prior to the 1-day workshop, at the end of the workshop, and at 4 and 12 months follow-up. The workshop consisted of lectures and discussion groups; in the discussion groups, concepts were clarified, cases presented, and barriers to optimal cancer pain management identified. RESULTS: Significant improvements in attitudes (P < 0.01), knowledge (P < 0.01), and total scores (P < 0.002) were observed when the preworkshop responses were compared with those obtained immediately after instruction. Scores on the questionnaire were the same or slightly better at both 4 and 12 months in follow-up, demonstrating no loss in acquired knowledge or attitude. Comparison of the postworkshop scores with those at 12 months follow-up were significantly better in attitude (P < 0.03), and in total score (P < 0.01); improvements in knowledge also approached significance (p < 0.06). These represented continuing improvements because significant differences in the attitude scores (P < 0.05) and the total score (P < 0.05) were observed when the 4-month and 12-month follow-up responses were evaluated. The effectiveness of the program in the transference of knowledge was also measured; in the first year of the program, more than 4500 health-care professionals were subsequently informed about cancer pain management from the Role Model Participants. CONCLUSIONS: Significant improvements were observed immediately in both attitude and knowledge of cancer pain management principles after the 1-day Role Model Workshop. These improvements continued, as determined at 4 and 12 months follow-up. The Role Model Participants were highly motivated to share the learned principles of cancer pain management with other health-care professionals. These results are consistent with other Role Model Programs that both instruct and involve the participants. The Role Model Program is an efficient and effective means of educating health-care professionals in the concepts of cancer pain management.

Analgesia↗
PubMed1996

Cerebrospinal fluid distribution of opioids after intraventricular & lumbar subarachnoid administration in sheep.

The study of opioid distribution in blood and cerebrospinal fluid (CSF) is required to understand pharmacokinetic-pharmacodynamic relationships following lumbar intrathecal (it) and intracerebroventicular (i.c.v.) administration, and to investigate the contributions of spinal or supraspinal sites of action. The sheep model developed for pharmacokinetic study of analgesics allows atraumatic sampling of plasma and CSF after drug administration by the intravenous (i.v.), i.c.v., and it routes in an unanesthetized animal. Five adult female sheep were prepared with femoral vascular catheters, lumbar it and epidural cannulae, i.c.v. cannulae, and cisterna magna cannulae. Hydromorphone, methadone, naloxone, and [14C] sucrose were injected and collected by two methods: 1) injection into the i.c.v. cannula with lumbar CSF samples collected via the lumbar cannula and 2) injection into the lumbar cannula and cisternal CSF samples collected via ventriculocisternal cannula. Hydromorphone, morphine, and [14C] sucrose were detected at 90-105 min in lumbar CSF after i.c.v. injection. Hydromorphone and [14C] sucrose were detected in i.c.v. cerebrospinal fluid at 50 min after lumbar i.t. injection. Methadone was not detected in i.c.v. cerebrospinal fluid after i.t. injection, nor was methadone significantly detected in lumbar CSF after i.c.v. injection. These data indicate that i.c.v. and i.t. administration of lipophilic opioids produces CSF distributions different from those of hydrophilic opioids. This suggests that lipophilic opioids such as methadone or naloxone exert their effects predominantly on tissues near the site of injection. The study of i.t. and i.c.v. opiate administration and CSF pharmacokinetics may therefore have direct clinical implications.

Analgesics, Opioid↗
PubMed1996

Inappropriate use of naloxone in cancer patients with pain.

Opioid overdose is rarely the primary cause of altered mental status in cancer patients receiving opioid therapy. The inappropriate administration of naloxone to reverse an abnormal mental status can cause severe withdrawal symptoms and pain. To illustrate this problem, we report the case of a patient inappropriately treated with naloxone and the results of a retrospective review of the medical records of 15 consecutive patients with cancer treated with naloxone in the emergency department over a 5-month period. We offer guidelines for a more thoughtful approach to the management of patients with cancer who present with encephalopathy.

Aged↗
PubMed1996

Latencies of calcium elevation and depolarization in Limulus ventral photoreceptors injected with GDP-beta S.

We have used confocal fluorescence microscopy and fluorescent calcium indicators to investigate the relationship between light-induced elevation of intracellular calcium ion concentration (Cai) and depolarization in small volumes of cytosol close to the microvillar plasma membrane of the ventral photoreceptor of Limulus polyphemus. We prolonged the latency of the light response by treatment of cells with hydroxylamine and injection of the G-protein blocker, guanosine-5'-O-(2-thiodiphosphate (GDP-beta S). Such treatment increased the latency of the cell's response from approximately 20 to 50 ms. In both treated and untreated cells we observed a close correlation between the times at which we first detected the electrical response and the elevation of Cai. We obtained 18 out of 54 and 12 out of 22 recordings, in untreated and treated cells respectively, for which the elevation of Cai was detected simultaneous with, or 1-4 ms prior to, the electrical response to light. The prolonged latent period exhibited by treated cells may make possible future investigation of the effects on the initial response to light of local photolytic release of caged compounds at the microvillar membrane.

Aniline Compounds↗
PubMed1996

Limulus ventral photoreceptors contain two functionally dissimilar inositol triphosphate-induced calcium release mechanisms.

Injections of inositol 1,4,5 triphosphate (InsP3) into Limulus ventral photoreceptors give rise to a rapid depolarization and an elevation of intracellular calcium concentration (Cai). This response to InsP3 is followed by a period of desensitization that persists as long as Cai remains elevated (feedback inhibition). Limulus ventral photoreceptors have two types of lobe: a light-sensitive rhabdomeric lobe (R lobe), and a light-insensitive arhabdomeric lobe (A lobe). Evidence showing the presence of feedback inhibition has been so far demonstrated only in the R lobe. In this study, simultaneous measurements of Cai were made using aequorin and double-barreled calcium-sensitive electrodes in each type of lobe. We carefully checked the location of the R lobe and A lobe by scanning a microspot of light across the whole photoreceptor. We then inserted a double-barreled calcium-sensitive microelectrode with InsP3 in either type of lobe. In the R lobe, injections of InsP3 led to a large Cai increase, a rapid depolarization and feedback inhibition; a brief flash of light induced a rapid depolarization and a Cai increase measured by both aequorin and the calcium-sensitive electrode. In the A lobe, injection of InsP3 led to an increase in Cai measured by the calcium-sensitive electrode but to no depolarization or aequorin luminescence. Further there was no evidence of feedback inhibition in the A lobe; the elevation of Cai caused by the first injection did not desensitize the photoreceptor to a second injection of InsP3 3 s later. To verify that the aequorin and the cell membrane respond to an increase in Cai, we presented a brief flash of light. Following a uniform illumination, there is indeed a typical large luminescence increase and a receptor potential. The calcium-sensitive electrode measures a small and slow Cai increase because its tip is located in the A lobe and it is measuring Ca2+ diffusing from the R lobe. Our observation that the InsP3-induced Cai increase in the A lobe is not apparently accompanied by a subsequent desensitization to InsP3 may suggest that there are more than one type of InsP3 receptor in the same cell. Alternatively, the InsP3 receptor could be the same but some additional factor, which confers feedback inhibition, could be missing in the A lobe.

Aequorin↗
PubMed1996

Commissural myelotomy for intractable cancer pain: report of two cases.

PATIENTS: We describe two patients with cancer-related low back and bilateral lower extremity pain that failed pharmacologic treatment. RESULTS: In both cases, commissural myelotomy provided significant pain relief. The role of myelotomy in the management of cancer pain is discussed.

Carcinoma, Hepatocellular↗
PubMed1995

Light activated calcium release in Limulus ventral photoreceptors as revealed by laser confocal microscopy.

Using confocal imaging and fluorescent calcium indicators, light-induced elevation of intracellular Ca2+ concentration ([Ca2+]i) in Limulus ventral photoreceptors was shown to be initiated within 4 microns of the light-sensitive plasma membrane. Within 500 ms, elevation of [Ca2+]i spread throughout the light-sensitive rhabdomeral lobe of the photoreceptor, but barely penetrated the arhabdomeral lobe. During saturating illumination of measurement spots near the plasma membrane, [Ca2+]i rose at rates of 1-2 mM/s after a latent period of 14-40 ms, reaching peak concentrations of approximately 150 microM. Rapid elevation of [Ca2+]i persisted in the absence of extracellular Ca2+ and was therefore ascribed to release from intracellular stores. The elevation of [Ca2+]i was always detectable within 5 ms of the electrical response of the photoreceptor to light. In 14 out of 54 measurements, detection of elevated calcium preceded the electrical response. Cyclopiazonic acid, an inhibitor of endoplasmic reticulum Ca-pumps, greatly reduced the elevation of [Ca2+]i during bright flashes and the sensitivity of the electrical response to dim flashes. However, the maximal response to bright flashes was not diminished. Therefore, although the calcium release that we detect may be fast enough to contribute to the electrical response we are unable to demonstrate that it is absolutely required.

Animals↗
PubMed1995

Measurement of cytosolic Ca2+ concentration in Limulus ventral photoreceptors using fluorescent dyes.

Several Ca-sensitive fluorescent dyes (fura-2, mag-fura-2 and Calcium Green-5N) were used to measure intracellular calcium ion concentration, Cai, accompanying light-induced excitation of Limulus ventral nerve photoreceptors. A ratiometric procedure was developed for quantification of Calcium Green-5N fluorescence. A mixture of Calcium Green-5N and a Ca-insensitive dye, ANTS, was injected in the cell and the fluorescence intensities of both dyes were used to calculate the spatial average of Cai within the light-sensitive R lobe of the photoreceptor. In dark-adapted photoreceptors, the initial Cai was 0.40 +/- 0.22 microM (SD, n = 7) as measured with fura-2. Cai peaked in the light-sensitive R lobe at 700-900 ms after the onset of an intense measuring light step, when the spatial average of Cai within the R lobe reached 68 +/- 14 and 62 +/- 37 microM (SD, n = 5) as measured with mag-fura-2 and Calcium Green-5N, respectively. The rate of Cai rise was calculated to be approximately 350 microM/s under the measuring conditions. The resting level of Mg2+ was estimated to be 1.9 +/- 0.9 mM, calculated from mag-fura-2 measurements. To investigate the effect of adapting light on the initial Cai level in the R lobe, a 1-min step of 420 nm background light was applied before each measurement. The first significant (P < 0.05) change in the initial level of Cai occurred even at the lowest adapting light intensity, which delivered approximately 3 x 10(3) effective photons/s. The relative sensitivity of the light-adapted photoreceptors was linearly related to the relative Cai on a double log plot with slope between -4.3 and -5.3. We were unable to detect a Cai rise preceding the light-activated receptor potential. The Cai rise, measured with Calcium Green-5N, lagged 14 +/- 5 ms (SD, n = 32) behind the onset of the receptor potential at room temperature in normal ASW. In the absence of extracellular Ca2+ and at 10 degrees C, this lag increased to 44 +/- 12 ms (SD, n = 17).

Animals↗
PubMed1995

Guidelines for the clinical use of transdermal fentanyl.

Transdermal (TTS) fentanyl therapy has emerged as an effective alternative to the use of oral opioids for the control of pain in certain cancer patients. These patients are those with moderate to severe chronic pain, with a stable baseline pain pattern. Patients receiving this treatment should first be titrated to stable pain relief with oral opioids and should have recourse during therapy to fast-acting, short-duration analgesics for the control of incident pain. TTS fentanyl dosing schedules should be based upon the patient's requirement for rescue dosing and duration of effective pain control. The average requirement to change fentanyl patches is every 72 h, although 48-h dosing is necessary in a few patients. This novel route of fentanyl administration allows convenient outpatient treatment, the possibility of a lower incidence of side effects, and may thus aid compliance.

Administration, Cutaneous↗
PubMed1995

Subarachnoid neurolytic block under general anesthesia in a 3-year-old with neuroblastoma.

CASE REPORT: A 3-year-old boy with neuroblastoma complained of severe pain in the left lower extremity. Pharmacologic management had previously been attempted, but severe pain continued, and further upward titration was complicated by sedative effects. METHODS AND RESULTS: Because the focus of treatment had become the controlling of pain, a lumbosacral subarachnoid neurolytic block was performed under general anesthesia. One-time neurolysis was more acceptable to the family than a procedure like epidural analgesia, that requires greater management. Contrast medium was used to monitor the spread of the neurolytic. An epidural catheter was inserted during the neurolytic block procedure for possible future use. The short-term results were good--pain reports and opioid doses decreased greatly, although with increased incontinence. The boy had new abdominal distention and pain 5 days after neurolysis. Opioid doses and sedatives were increased. He died 3 days later.

Anesthesia, General↗
PubMed1994

Unambiguous total synthesis of the enantiomers of myo-inositol 1,3,4-trisphosphate: 1L-myo-inositol 1,3,4-trisphosphate mobilizes intracellular Ca2+ in Limulus photoreceptors.

Syntheses of the enantiomers of myo-inositol 1,3,4-trisphosphate are described. 1,4-Di-O-allyl-myo-inositol was regioselectively p-methoxybenzylated at the 3-position to give 1,4-di-O-allyl-3-O-(p-methoxybenzyl)-myo-inositol followed by benzylation of the remaining free hydroxyl groups to give the key intermediate 1,4-di-O-allyl-2,5,6-tri-O-benzyl-3-O-(p-methoxybenzyl)-myo-inositol. Removal of the p-methoxybenzyl and allyl groups gave 2,4,5-tri-O-benzyl-myo-inositol which was phosphitylated with bis(benzyloxy)(diisopropylamino)phosphine to give the fully protected trisphosphite triester. Oxidation using tert-butyl hydroperoxide gave 2,5,6-tri-O-benzyl-1,3,4-tris(dibenzylphospho)-myo-inositol, and deprotection using sodium in liquid ammonia gave racemic myo-inositol 1,3,4-trisphosphate. Deprotection of the key intermediate 1,4-di-O-allyl-2,5,6-tri-O-benzyl-3-O-(p-methoxybenzyl)-myo-inositol by isomerization of allyl groups followed by mild acid hydrolysis gave 2,4,5-tri-O-benzyl-1-O-(p-methoxybenzyl)-myo-inositol, which was converted to the diastereoisomeric (bis-(-)-camphanates. The diastereoisomers were separated by column chromatography and the camphanates and the p-methoxybenzyl group removed by saponification and acid hydrolysis, respectively, for each diastereoisomer to give the enantiomers of 2,4,5-tri-O-benzyl-myo-inositol. The absolute configurations of the latter were established by conversion of 1L-2,5,6-tri-O-benzyl-3-O-(p-methoxybenyl)-myo-inositol to the known 1L-1,2,4,5,6-penta-O-benzyl-myo-inositol. Phosphorylation and deblocking gave the D- and L-enantiomers of myo-inositol 1,3,4-trisphosphate. Biological evaluation in Limulus photoreceptors showed that 1L-myo-inositol 1,3,4-trisphosphate was much more active than the D-enantiomer, producing repetitive bursts of depolarization due to mobilization of intracellular calcium.

Animals↗