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Biomedical subjects

K M Foley

Publications and source records attributed to K M Foley.

At least 55 records · Page 3Linked to original sources
PubMed1991

Chronic nausea and morphine-6-glucuronide.

Morphine-6-glucuronide is an active metabolite of morphine that has analgesic properties and is measurable in the plasma and cerebrospinal fluid of patients treated with this opioid. Decreased clearance of the compound has been observed in patients with renal insufficiency, and this has been associated with an increase in the ratio of morphine-6-glucuronide to morphine. Clinical effects from accumulation of morphine-6-glucuronide have not been described with the exception of case reports in which patients with renal failure were noted to develop opioid toxicity with high plasma levels of the metabolite and low levels of the parent drug. We describe a patient who experienced chronic nausea and an episode of confusion while treated with a small, stable dose of oral morphine in the setting of mild renal insufficiency. Relatively high levels of morphine-6-glucuronide were measured and all symptoms resolved promptly as the concentration of this metabolite declined. This case provides suggestive evidence that morphine-6-glucuronide can produce clinically significant effects in patients with mild renal insufficiency.

Adenocarcinoma↗
PubMed1991

Chronic morphine therapy for cancer pain: plasma and cerebrospinal fluid morphine and morphine-6-glucuronide concentrations.

Morphine-6-glucuronide (M-6-G) is an active metabolite that may contribute to the clinical effects produced by systemic administration of morphine. To help clarify the extent to which M-6-G may cross the blood-brain barrier and exert effects, we employed high-performance liquid chromatography with electrochemical detection to measure the concentrations of M-6-G and morphine in the plasma and either ventricular (three patients) or lumbar (eight patients) CSF of cancer patients receiving chronic morphine therapy. The mean ratio of morphine in ventricular CSF:morphine in plasma was 0.71; the same ratio for M-6-G was only 0.077. The average molar ratio of M-6-G: morphine in ventricular CSF was 0.207, and the average molar ratio in plasma was 1.89. Although sampling problems render the lumbar CSF results less reliable, they were very similar. Thus, plasma contained approximately twice as much M-6-G as morphine, whereas CSF contained only one-fifth to one-third as much. These data confirm that M-6-G in plasma is distributed into CSF, but to a far lesser extent than morphine. They help explain animal data demonstrating much higher potency of M-6-G on administration into CSF than systemic administration and indicate that the degree to which M-6-G contributes to morphine effects in humans remains an unresolved question.

Adult↗
PubMed1990

Character of terminal illness in the advanced cancer patient: pain and other symptoms during the last four weeks of life.

There is a great variability among advanced cancer patients in the experience of symptoms and their impact on life's activities. A subgroup of difficult patients particularly tax the clinical skills and compassion of practitioners. Although the need for information about these patients is evident, their characteristics have not been explored heretofore. We describe our experience with such patients, a group referred to the Supportive Care Program of the Pain Service at Memorial Sloan-Kettering Cancer Center. Prevalence of pain and other symptoms, patterns of opioid use and routes of drug administration, and the prevalence of suicidal ideation and requests for euthanasia are discussed.

Adult↗
PubMed1990

Pharmacokinetic-pharmacodynamic relationships of methadone infusions in patients with cancer pain.

To determine the relationship between changes in plasma methadone concentration and pharmacodynamic effects, plasma methadone profiles and pharmacodynamics (analgesia and sedation) were measured during and after the continuous infusion of methadone for 180 to 270 minutes in 15 patients with pain caused by cancer. An increase in plasma methadone concentration resulted in a rapid increase in pain relief or sedation. The estimates of values of 50% of maximum effect (Css50) for pain relief and sedation obtained with a pharmacokinetic-pharmacodynamic model varied tenfold to twentyfold among patients; the mean Css50 value for pain relief (0.359 +/- 0.158 [SD] micrograms/ml) was virtually the same as the mean Css50 value for sedation (0.336 +/- 0.205 [SD] micrograms/ml). Similarly, the mean gamma (slope function) for pain relief (4.4 +/- 3.8 [SD]) and sedation (5.8 +/- 5.4 [SD]) did not differ. Examination of hysteresis plots of data obtained during the infusion and for 4 to 5 hours after cessation of the infusion revealed a very rapid equilibration between plasma methadone values and the sites mediating pain relief. There was no indication of the development of tolerance to the pharmacodynamic effects of methadone during the study. This report describes a method for quantitating the pharmacokinetic-pharmacodynamic relationships of the desirable and undesirable effects of opioid analgesics.

Adult↗
PubMed1990

Neurologic pain syndromes in patients with cancer.

One third of cancer patients in active therapy and two thirds of patients with far-advanced disease have significant pain. A series of specific neurologic pain syndromes occur in this population and are unique to this pain population. Early diagnosis and treatment are critical to prevent irreversible neurologic damage and chronic neuropathic pain.

Humans↗
PubMed1989

Controversies in cancer pain. Medical perspectives.

The treatment of pain in the patient with cancer has focused attention on a series of controversial issues involving medical, social, and moral factors. The medical factors include a lack of knowledge on the part of health care professionals regarding the rational use of opioid drugs. This is coupled with real limitations in the general understanding of the mechanisms of pain and its treatment using pharmacologic, anesthetic, and neurosurgical approaches. Several pharmacologic controversies, including the choice of drug, route and method of administration, and tolerance development and risk of substance abuse, have emerged with the use of opioids on a chronic basis in the cancer population. The social and moral implications involve the issue of who will pay for high technology pain management approaches for patients either at home or in hospice care and the ethical considerations in managing pain with opioid drugs. Carefully designed studies to assess these factors, coupled with broad educational programs, will improve the care of cancer patients in pain and expand our understanding of these important issues.

Analgesics, Opioid↗
PubMed1989

Pain control in breast cancer. A panel discussion.

Pain can be a prominent finding in breast cancer patients. It may occur in the setting of the postmastectomy period, related to the disruption of normal neural pathways or the development of lymphedema. In advanced disease, the management of pain from nerve compression or bone metastases requires special approaches. In this panel discussion, the participating physicians will discuss these topics and provide an up-to-date approach to pain control in breast cancer patients.

Analgesics, Opioid↗
PubMed1989

Cancer pain management with a controlled-release oral morphine preparation.

An open-label pilot study was conducted to assess the efficacy and acceptability of a controlled-release oral morphine formulation, MS Contin tablets, when administered "by the clock" two to three times daily as a substitute for opioids given on request to patients with pain caused by advanced cancer. Initially, four-hourly does of standard "immediate-release" oral morphine sulfate tablets were substituted for the patients' prior analgesic medication and titrated to individual needs. Forty of the 47 patients enrolled in the study were subsequently switched to an eight-hourly MS Contin regimen (three patients became too ill to continue the study, and four left the study during the immediate-release titration phase because of adverse reactions that may have been drug related). Small "rescue" doses of standard oral morphine were available to the patients, but they were taken infrequently. Twenty-one of the 37 patients maintained on the eight-hourly schedule consented to be treated with, and were subsequently stabilized on, MS Contin administered every 12 hr, with a reduction of over 20% in their average daily morphine dose. Most of the patients rated the controlled-release medication superior to the standard oral morphine tablets in terms of both convenience and adequacy of relief.

Administration, Oral↗
PubMed1989

Management of pain in pancreatic cancer.

Potentially useful modalities of pain control in pancreatic cancer include antitumor therapy, pharmacotherapy, celiac plexus block, splanchnic nerve block, intercostal nerve block, and psychological intervention. These modalities are often used concurrently in treating the multiple dimensions that affect pain. Although thorough assessments are lacking, preliminary data suggest that antitumor chemotherapy and radiotherapy and celiac plexus block are especially useful modalities of pain control in these patients. The optimal time in the disease course for intervention with celiac plexus block is not known. Further studies are needed to clarify the nature of pain syndromes involved and the role of the various therapeutic modalities.

Analgesics↗
PubMed1989

Neurologic pain syndromes in patients with cancer.

Recognizing and treating the cause of pain in the patient with cancer should be the initial approach to the management of this common symptom. Careful analysis of patients with cancer and pain has led to the elucidation of common neurologic pain syndromes unique to this disease process. Pain in patients with cancer is commonly the presenting symptom of neurologic involvement. Changes in the pattern of pain or neurologic deficits should be carefully evaluated to rule out the possibility that metastatic disease may be exacerbating existing neuropathic pain. This chronic intractable pain syndrome can markedly debilitate the patient and needs an aggressive approach with drug therapy as the first-line approach.

Chronic Disease↗
PubMed1989

Guidelines for use of controlled-release oral morphine in cancer pain management. Correlation with clinical experience.

An open study of 47 patients with cancer pain treated with repeated doses of a controlled-release oral morphine tablet was conducted to assess the acceptability of this drug and develop guidelines for its use. Each patient kept a detailed record of pain, analgesic intake, side effects, and other medications. A nurse observer/clinician followed these patients on a daily basis and kept similar records. Of 47 patients who began the study, 37 were successfully stabilized with standard morphine sulfate tablets and then switched to controlled-release morphine (CRM). Twenty-one patients who completed the study took CRM every 12 h, and 16 patients received a dose every 8 h. Doses of the CRM ranged from 30 mg every 12 h to 360 mg every 8 h. Less frequent doses and uninterrupted sleep were reported advantages. All of the patients completing the study chose to continue this method of pain management and extended care data were obtained from each patient poststudy through continued monitoring.

Administration, Oral↗
PubMed1988

Leukemic relapse presenting as sciatic nerve involvement by chloroma (granulocytic sarcoma).

A relapse of acute nonlymphocytic leukemia in a child presented as subacute mononeuropathy involving the sciatic nerve. Surgical exploration showed a chloroma (granulocytic sarcoma) of the distal sciatic nerve, but resection and irradiation did not lead to recovery of nerve function or complete resolution of the patient's symptomatic neuropathic pain. This case represents a rare neurologic complication of what is currently an uncommon presentation for leukemic relapse, and may be the only reported case of chloromatous involvement of the peripheral nervous system (PNS) without coexisting epidural or leptomeningeal leukemia.

Child↗
PubMed1988

Sublingual absorption of selected opioid analgesics.

Ongoing interest in the improvement of pain management with opioid analgesics had led to the investigation of sublingual opioid absorption. The present report determined the percent absorption of selected opioid analgesics from the oral cavity of normal subjects under conditions of controlled pH and swallowing when a 1.0 ml aliquot of the test drug was placed under the tongue for a 10-minute period. Compared with morphine sulfate at pH 6.5 (18% absorption), buprenorphine (55%), fentanyl (51%), and methadone (34%) were absorbed to a significantly greater extent (p less than 0.05), whereas levorphanol, hydromorphone, oxycodone, heroin, and the opioid antagonist naloxone were not. Overall, lipophilic drugs were better absorbed than were hydrophilic drugs. Plasma morphine concentration-time profiles indicate that the apparent sublingual bioavailability of morphine is only 9.0% +/- 11.9% (SD) of that after intramuscular administration. In the same subjects the estimated sublingual absorption was 22.4% +/- 9.2% (SD), indicating that the sublingual absorption method may overestimate apparent bioavailability. When the oral cavity was buffered to pH 8.5, methadone absorption was increased to 75%. Thus, an alkaline pH microenvironment that favors the unionized fraction of opioids increased sublingual drug absorption. Although absorption was found to be independent of drug concentration, it was contact time dependent for methadone and fentanyl but not for buprenorphine. These results indicate that although the sublingual absorption and apparent sublingual bioavailability of morphine are poor, the sublingual absorption of methadone, fentanyl, and buprenorphine under controlled conditions is relatively high.

Administration, Sublingual↗
PubMed1988

Pain syndromes in multiple sclerosis.

To determine the prevalence and nature of pain in multiple sclerosis, we evaluated by questionnaire, interview, and chart review 159 patients residing in Middlesex County and followed in the MS Clinic at University Hospital, London, Ontario, Canada. Eighty-eight patients (55%) had either an acute or chronic pain syndrome at some time during their disease. Fifteen patients (9%) with acute pain syndromes had episodes of paroxysmal tic-like pain diagnosed in seven as trigeminal neuralgia. Chronic pain syndromes, present for a mean duration of 4.9 years, occurred in 76 patients (48%) and included dysesthetic extremity pain (29%), back pain (14%), painful leg spasms (13%), and abdominal pain (2%). MS patients with pain were similar to the pain-free group in mean age of onset (34.0 versus 31.9 years), average duration of disease (13.3 versus 12.1 years), spinal cord involvement (97% for each group), and mean rating on Kurtzke Disability Status Scale (4.2 versus 3.5). They differed in sex ratio with a higher female-to-male ratio in the pain group (3:1 versus 1.4:1). Chronic pain is a common feature of well-established MS and is usually associated with a myelopathy. Therapy must be individualized for each specific pain syndrome.

Acute Disease↗
PubMed1988

Vitamin A is stored as fatty acyl esters of retinol in the lacrimal gland.

Many tissues which require vitamin A store the vitamin as long-chain fatty acyl esters of retinol. As part of a study designed to characterize vitamin A metabolism in the lacrimal gland, which transports retinol from blood to lacrimal gland fluid, extracts from lacrimal glands of rabbits and rats were analyzed by non-aqueous high performance liquid chromatography. Retinyl linoleate, retinyl palmitate, and retinyl stearate were identified in these extracts by their co-elution with standards, their retention time relative to retinyl palmitate, and their susceptibility to hydrolysis by saponification. Retinyl palmitate was present in rabbit lacrimal gland at 51.0 +/- 10.1 ng/g tissue. After treatment of vitamin A-deficient rabbits with orally administered [11,12-3H] retinyl acetate, the radiolabeled esters retinyl linoleate, palmitate, and stearate were extracted from the lacrimal glands. These data show that the lacrimal gland stores vitamin A as fatty acyl esters of retinol.

Animals↗