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Biomedical subjects

Richard Payne

Publications and source records attributed to Richard Payne.

30 records · Page 2Linked to original sources

Reflective practice and palliative care education: a clerkship responds to the informal and hidden curricula.

The authors discuss the damaging influence of informal and hidden curricula on medical students and describe a two-week clerkship in palliative care and clinical ethics at their school (Weill Medical College of Cornell University). This required clerkship, begun in 1999, uses reflective practice and a special pedagogic technique, participant observation, to counteract the influences of the informal and hidden curricula. This technique seeks to immerse the participant observer in the context of care. In their role as participant observers, students are relieved of any direct clinical responsibilities for two weeks so they have time for the careful observation and reflection required and also can consider the humanistic dimensions of practice, which are often displaced by the need to master diagnostic and therapeutic skills. Course objectives include identifying psychosocial and contextual factors that influence care, principles of pain and symptom management, and ethical and legal issues at the end of life. Students are expected to learn how to apply ethical norms to patient care, describe methods of pain and symptom management, communicate in an effective and humanistic manner, and articulate models of patient-centered advocacy. The clerkship fosters professionalism in patient care, appreciation of cultural diversity, and the student's ability to assume responsibility for developing competency in these areas. Although it is too early to know whether this clerkship will ultimately affect the practice patterns of students who experience it, short-term evaluation has been very favorable.

Clinical Clerkship↗

Benefit-risk assessment of transdermal fentanyl for the treatment of chronic pain.

Transdermal fentanyl is effective and well tolerated for the treatment of chronic pain caused by malignancy and non-malignant conditions when administered according to the manufacturer's recommendations. Compared with oral opioids, the advantages of transdermal fentanyl include a lower incidence and impact of adverse effects (constipation, nausea and vomiting, and daytime drowsiness), a higher degree of patient satisfaction, improved quality of life, improved convenience and compliance resulting from administration every 72 hours, and decreased use of rescue medication. Transdermal fentanyl is a useful analgesic for cancer patients who are unable to swallow or have gastrointestinal problems. Transdermal fentanyl forms a depot within the upper skin layers before entering the microcirculation. Therapeutic blood levels are attained 12-16 hours after patch application and decrease slowly with a half-life of 16-22 hours following removal. Patients with chronic pain should be titrated to adequate relief with short-acting oral or parenteral opioids prior to the initiation of transdermal fentanyl in order to prevent exacerbations of pain or opioid-related adverse effects. Transdermal fentanyl can then be initiated based on the 24-hour opioid requirement once adequate analgesia has been achieved. The prolonged elimination of transdermal fentanyl can become problematic if patients develop opioid-related adverse effects, especially hypoventilation. Adverse effects do not improve immediately after patch removal and may take many hours to resolve. Patients who experience opioid-related toxicity associated with respiratory depression should be treated immediately with an opioid antagonist such as naloxone and closely monitored for at least 24 hours. Because of the short half-life of naloxone, sequential doses or a continuous infusion of the opioid antagonist may be necessary. Transdermal fentanyl should be administered cautiously to patients with pre-existing conditions such as emphysema that may predispose them to the development of hypoventilation. Transdermal fentanyl is indicated only for patients who require continuous opioid administration for the treatment of chronic pain that cannot be managed with other medications. It is contraindicated in the management of acute and postoperative pain, as pain may decrease more rapidly in these circumstances than fentanyl blood levels can be adjusted, leading to the development of life-threatening hypoventilation. Cognitive and physical impairments such as confusion and abnormal co-ordination can occur with transdermal fentanyl. Therefore, patients should be instructed to refrain from driving or operating machinery immediately following the initiation of transdermal fentanyl, or after any dosage increase. Patients may resume such activities once the absence of these potential adverse effects is documented.

Administration, Cutaneous↗

Neuropathic pain in patients with cancer.

We provide a detailed description of painful neural lesions in hospitalized patients with cancer. A total of 187 consecutive patients with cancer and pain, referred to the pain service of a cancer hospital, were evaluated within 24 hours by two neurologists and followed until discharge or death. Based on history, pain descriptors, physical examination, and radiological and electrophysiological studies, the pain was categorized as neuropathic in 103 patients. The most frequent sites of neurological injury were nerve roots, spinal cord and cauda equina, brachial and lumbosacral plexus, and peripheral nerves. There were no patients with pain caused by injury to the brain. In 93 of these patients, the pain was caused by ongoing neural injury, while, in 10 patients, the neural injury was old and stable. Within these two groups of patients with neuropathic pain, analgesic treatments differed. Prospective studies may determine if categorizing painful neurological injuries in cancer patients based on inferred pathophysiology is useful when deciding among different treatment options.

Adolescent↗

Protein kinase C-induced disorganization and endocytosis of photosensitive membrane in Limulus ventral photoreceptors.

Protein kinase C (PKC) desensitizes the light response in photoreceptors from the ventral optic nerve of the horseshoe crab Limulus. Photoisomerization of Limulus rhodopsin leads to phosphoinositide hydrolysis, resulting in the production of inositol trisphosphate and diacylglycerol (DAG). Inositol trisphosphate mobilizes intracellular stores of Ca(2+), resulting in photoreceptor excitation in Limulus, while DAG may activate PKC. We investigated whether PKC-mediated desensitization of the photoresponse is accompanied by ultrastructural changes in the rhodopsin-bearing photosensitive membrane (rhabdom) in Limulus ventral photoreceptors. PKC activation by (-)-indolactam V in darkness induces disorganization and swelling of the rhodopsin-containing microvilli and endocytosis of rhabdomeral membrane. The effects of (-)-indolactam V on dark-adapted photoreceptor ultrastructure are reversible, are stereospecific, are blocked by coapplication of PKC inhibitors, and closely match those induced by continuous, bright light. Rhabdom disorganization and endocytosis via PKC activation may, therefore, contribute to desensitization of the light-adapted photoreceptor.

Animals↗

Simultaneous roles for Ca2+ in excitation and adaptation of Limulus ventral photoreceptors.

The ventral photoreceptors of Limulus have been one of the main preparations for the study of invertebrate phototransduction. The study of ventral photoreceptors has revealed that they have remarkable performance characteristics, most notably the very large amplification of the transduction process. This amplification is critically dependent upon the coupling of photoactivated rhodopsin to the phosphoinositide cascade, resulting in the release of Ca2+ from intracellular stores. The consequent elevation of Ca2+ within the photoreceptor's cytosol is amongst the most rapid and dramatic known to be activated by the phosphoinositide cascade. This review summarizes the evidence that intracellular Ca2+ is a key regulator of transduction in Limulus photoreceptors. The mechanisms that regulate Ca2+ as well as the possible targets of the action of Ca2+ are reviewed. Ca2+ elevation is critical for triggering both excitation and adaptation processes in the photoreceptor. The question of how a single second messenger can produce these two opposing effects is of obvious interest and is a topic dealt with throughout this review.

Animals↗

Pitfalls of opioid rotation: substituting another opioid for methadone in patients with cancer pain.

The successful use of methadone in cancer pain has been supported by numerous case reports and clinical studies. Methadone is usually used as a second or third line opioid medication. As the use of methadone increases we are facing the challenge of converting methadone to other opioids as part of sequential opioid trials. Data on the equianalgesic ratios for the substitution of other opioids for methadone are lacking. We present prospective data on 13 consecutive rotations from methadone to a different opioid. The opioid rotation was followed by escalation of pain and/or severe dysphoria, not controlled by a rapid increase in the dose of the second opioid, in 12 of the 13 patients. Only one patient was successfully maintained on the second opioid after the discontinuation of methadone, while 12 patients required a switch back to methadone. We conclude that opioid rotation from methadone to another opioid is often complicated by worsening pain and dysphoria. These symptoms may not improve despite upward titration of the second opioid. A uniformly accepted conversion ratio for substituting methadone with another opioid is currently not available. More data on the rotation from methadone to other opioids are needed.

Adult↗

Lymphomatous meningitis presenting as atypical cluster headache.

We report a woman who developed atypical cluster headache as the first manifestation of trigeminal dysfunction from leptomeningeal lymphoma. Progression to a complete trigeminal neuropathy led to resolution of her pain. The role of the trigeminal nerve in the expression of the signs and symptoms of cluster headache is discussed.

Brain Neoplasms↗

Direct decompressive surgical resection in the treatment of spinal cord compression caused by metastatic cancer: a randomised trial.

BACKGROUND: The standard treatment for spinal cord compression caused by metastatic cancer is corticosteroids and radiotherapy. The role of surgery has not been established. We assessed the efficacy of direct decompressive surgery. METHODS: In this randomised, multi-institutional, non-blinded trial, we randomly assigned patients with spinal cord compression caused by metastatic cancer to either surgery followed by radiotherapy (n=50) or radiotherapy alone (n=51). Radiotherapy for both treatment groups was given in ten 3 Gy fractions. The primary endpoint was the ability to walk. Secondary endpoints were urinary continence, muscle strength and functional status, the need for corticosteroids and opioid analgesics, and survival time. All analyses were by intention to treat. FINDINGS: After an interim analysis the study was stopped because the criterion of a predetermined early stopping rule was met. Thus, 123 patients were assessed for eligibility before the study closed and 101 were randomised. Significantly more patients in the surgery group (42/50, 84%) than in the radiotherapy group (29/51, 57%) were able to walk after treatment (odds ratio 6.2 [95% CI 2.0-19.8] p=0.001). Patients treated with surgery also retained the ability to walk significantly longer than did those with radiotherapy alone (median 122 days vs 13 days, p=0.003). 32 patients entered the study unable to walk; significantly more patients in the surgery group regained the ability to walk than patients in the radiation group (10/16 [62%] vs 3/16 [19%], p=0.01). The need for corticosteroids and opioid analgesics was significantly reduced in the surgical group. INTERPRETATION: Direct decompressive surgery plus postoperative radiotherapy is superior to treatment with radiotherapy alone for patients with spinal cord compression caused by metastatic cancer.

Combined Modality Therapy↗

Desensitization of the photoresponse in Limulus ventral photoreceptors by protein kinase C precedes rhabdomere disorganization and endocytosis.

Limulus photoreceptors utilize the phosphoinositide pathway to generate light-induced single photon events (quantum bumps) that sum to form the depolarizing receptor potential. The protein kinase C (PKC) activator, (-)-indolactam V (ILV) rapidly desensitizes the light response in Limulus ventral nerve photoreceptors. Within 10 min of extracellular application, 100 nM (-)-ILV caused a decrease in the mean amplitude of quantum bumps to 38% of control values. PKC activation by (-)-ILV also causes photosensitive membrane disorganization and endocytosis. To investigate whether this precedes desensitization of the electrical response, we fixed cells after 10-min incubation with 25 microM (-)-ILV, a concentration sufficient to cause a 1000-fold desensitization of the receptor potential. The photosensitive microvilli of these photoreceptors remained narrow, densely packed, and well organized. Increasing the incubation time to 60 min did, however, induce disorganization and swelling of the microvilli and endocytosis of the photosensitive membrane, as previously reported. Measurement of membrane capacitance did not indicate a significant reduction in membrane area accompanying desensitization by (-)-ILV. PKC-induced reduction in light sensitivity therefore precedes the detection of ultrastructural changes in the rhabdomeral membrane and is not due to a net loss of membrane.

Animals↗