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Ten healthy subjects (four male) of mean age 31 years (range 25-40) took part in a randomized double-blind four-way crossover study to examine the cognitive and psychomotor effects of repeated oral doses of dextropropoxyphene and morphine. Four treatments were compared: dextropropoxyphene napsylate 100 mg, morphine sulphate 10 mg, lorazepam 0.5 mg and placebo. Four doses of each drug were given at 4-h intervals to each subject on four separate study days at least 1 week apart. Cognitive function was assessed using choice reaction time, number vigilance, memory scanning, immediate and delayed word recall, word recognition, picture recognition, critical flicker fusion threshold (CFFT) and subjective measures of alertness, calmness and contentment. Lorazepam impaired the speed of responding on all tasks in which speed was recorded (except digit vigilance) and increased subjective ratings of calmness. Morphine had one major effect, which was to increase the accuracy of responding on the choice reaction time task, at every assessment. Morphine produced some sporadic effects in other tests and an increase in subjective calmness. Dextropropoxyphene impaired performance on choice reaction time and picture recognition. These data show that oral morphine may enhance performance in some measures of cognitive function, whereas dextropropoxyphene (in usual therapeutic doses) seems more likely to cause impairment. Neither opioid has substantial effects on cognition and psychomotor function compared with lorazepam.

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Paracetamol is a safe drug which has been used as an in-vivo probe to determine phase II metabolism in a HIV+/AIDS population. Due to the biohazard nature of HIV-infected samples, a high performance liquid chromatography (HPLC) assay which offers minimal sample manipulation and maximal specificity was developed. This reverse-phase HPLC method uses wavelength-switching UV detection for the simultaneous determination of paracetamol and its glucuronide and sulfate metabolites in HIV-infected urine samples. The solvent systems involves a simple isocratic elution with a composition of 50 mM sodium acetate buffer, pH adjusted to 3.5; acetonitrile (96:4 v/v) modified with 0.35% trifluroacetic acid. The validated method is highly reproducible with an inter-assay variation of < 7%. This method also shows good precision and sensitivity, making it an ideal assay for phenotyping studies to determine the extent of glucurondiation and sulfation activities.

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An accurate assessment and where possible a precise diagnosis of the underlying mechanism in necessary for the effective management of pain in cancer. The majority of patients respond to oral analgesics, and the range of drugs required is not vast. Adjuvant analgesic drugs will be needed for the treatment of bone pain, visceral pain and neuropathic pain. For the remaining patients who present with difficult and occasionally intractable pain, a multidisciplinary approach using drug and non-drug measures will usually allow significant relief of symptoms.

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Three contrasting views are presented in three short papers: that a short period of oncology training should be mandatory for trainees in palliative medicine; that many disciplines are important in palliative medicine and training programmes should be tailored to the needs of individuals while recognizing that there will always need to be close cooperation between oncology and palliative medicine; and that a short period of training in palliative medicine should be mandatory for those wishing to pursue a career in oncology.

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Twelve subjects (3 male) took part in a randomised double-blind four way crossover study designed to examine the cognitive and psychomotor effects of single doses of dextroproxyphene. On four study days one week apart each subject received each study product (i) dextropropoxyphene napsylate 100 mg, (ii) dextropropoxyphene napsylate 200 mg, (iii) lorazepam 2 mg and (iv) placebo. Performance measures were simple reaction time, choice reaction time, number vigilance, memory scanning, word recall (immediate and delayed), word recognition, picture recognition, critical flicker fusion threshold (CFFT) and visual analogue scales of alertness, calmness and contentment. Lorazepam had a marked effect on the range of tests used illustrating the sensitivity of the best battery. This was in contrast to the effects of dextropropoxyphene. A dose related effect in CFFT was detected, the 200 mg dose producing a significant decrease in CFFT throughout the testing period. Dextropropoxyphene also showed a tendency to improve scores on the verbal memory tasks. These data indicate that dextropropoxyphene in the usual doses does not produce significant impairment of cognitive and psychomotor function.

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Twelve subjects (8 male) took part in a randomised double blind four way crossover design study comparing four treatments: (i) morphine sulphate 10 mg, (ii) morphine sulphate 15 mg, (iii) lorazepam 1 mg (positive control) and (iv) placebo. Cognitive function was assessed using choice reaction time, number vigilance, memory scanning, immediate and delayed word recall, word recognition, picture recognition, critical flicker fusion threshold (CFFT) and subjective measures of alertness, calmness and contentment. Lorazepam produced a marked impairment in the tests of attention and memory. CFFT was reduced from 1-4 h but this only reached significance at 4 hours. The subjective measures suggested impaired alertness but this did not reach significance. The effects of morphine were less dramatic; both doses of morphine produced significant impairment at 1 hour on tests of secondary memory retrieval (delayed word recall and picture recognition sensitivity). CFFT was reduced for the whole observation period (6 h) achieving statistical significance at 4 hours. Morphine 15 mg produced a significant improvement in accuracy on the choice reaction time test at the 2, 4 and 6 h assessments. These results show minimal impairment of cognitive and psychomotor function after single oral doses of morphine and with possible improvement in one test. Further studies are required to examine the effect of repeated doses.

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The time has come to evaluate critically our practice of cancer pain management and the assumptions on which it is based. We owe it to our patients to maximize the quality of their lives and to provide evidence for them that is based on a scientific approach rather than anecdotal experience. From the information available, opioids do have effects on cognitive and psychomotor function, and although many of these effects diminish once the patient is on a stable dose, the evidence suggests that baseline pretreatment levels are not achieved. In addition, the relationship between measurable effects and the performance of everyday tasks such as driving is unclear. The challenge we now face is to continue the improvements in cancer pain control achieved over the last 25 years. The management of the central adverse effects of opioids must be focused on accurate assessment and careful titration of opioids against pain. Adjuvant analgesic drugs and non-drug measures should be used whenever possible, and drugs should be chosen that will not contribute to existing difficulties. The appropriate use of psychostimulants has yet to be established as has the relative benefit of one opioid over another in cancer pain.

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Back pain resulting from spinal instability in metastatic bone disease can be difficult to alleviate by pharmacological methods and surgical intervention is frequently required. This paper discusses the treatment options with three illustrative case reports.

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There is an increasing trend toward providing palliative care services within general hospitals. The history and work of three hospital palliative care teams is reviewed, one in New York, one in London, and one in Ontario, Canada. The evolution, leadership, structure, functioning, and financing of the teams is discussed. Indicators of success and survival, principally financial support, leadership, and acceptability within hospitals, are considered. It is recommended that the service traditionally limited to oncology patients be extended to other patient groups. It is also recommended that, taking into account cultural and institutional differences, standardized mechanisms be adopted so that services can be systematically audited and changes implemented. Research and education will become increasingly important if services within hospitals are to survive.

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The neuroleptic malignant syndrome is a serious and potentially fatal complication of neuroleptic and other dopamine antagonist drugs that are commonly used in symptom control in advanced cancer. Its true incidence is underestimated. Diagnosis may be difficult as its presentation may mimic infection or advancing malignant disease.

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The Renal Transplant Team at Tulane University Medical Center has been involved in training a multispecialty group of Guatemalan physicians to perform renal transplantations in Guatemala. The purpose is to train the physicians in their own country, using available equipment and personnel so that they can perform successful operations in our absence. This paper is a review of the considerations involved in the initial renal transplantation done in Guatemala by the Tulane Renal Transplant Team. The need for a preliminary site visit was paramount. Personnel, facilities, and both surgical and anesthesia equipment and supplies were carefully evaluated. The recipient was a 22-year-old man with end-stage renal disease due to chronic glomerulonephritis. The donor was a healthy 33-year-old brother. This article is not intended to review renal transplantation in the United States, but to show what is feasible in a developing country where many drugs and equipment are not available.

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Ten subjects with hypertension received medroxalol, which blocks both alpha- and beta-adrenergic receptors, has intrinsic sympathomimetic beta 2-agonist properties and is a direct vasodilator. Renal function tests consisting of inulin clearance and p-amino hippuric acid (PAH) clearance, plasma renin activity (PRA) in recumbent and upright postures, and aldosterone excretion rate were performed. After intravenous medroxalol, inulin clearance and PAH clearance rose, renal vascular resistance fell, recumbent PRA was unchanged, and the rise in PRA with upright posture was blunted. After 1 mo on oral medroxalol, blood pressure was controlled while inulin clearance, PAH clearance, and renal vascular resistance were unchanged. The rise in PRA with upright posture remained blunted. Urinary aldosterone excretion was unchanged after 1 mo on medroxalol.

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A 37-year-old man presented with biopsy-proved rapidly progressive glomerulonephritis and a strongly positive fluorescent treponemal antibody result. The patient was treated with hemodialysis, plasmapheresis, methylprednisolone, and penicillin, with rapid improvement and stabilization of renal function. Antibody was eluted from the frozen renal tissue and demonstrated a strongly positive reaction to the treponemal antigen when used in the fluorescent treponemal antibody test. In addition, when specific rabbit antitreponemal antiserum was applied to the frozen renal sections, there was a strongly positive reaction. Although syphilis has been associated with membranous glomerulopathy and post-infectious glomerulonephritis, this appears to be the first case of latent syphilis in which rapidly progressive glomerulonephritis has been identified. The presence within the glomeruli of treponemal antigen and antitreponemal antibody supports the association of these two entities.

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A 57-year-old man with legionnaires' disease had acute renal failure as a result of nontraumatic rhabdomyolysis. This report documents an association between legionnaires' disease and rhabdomyolysis, an association only rarely suggested previously. The mechanism of rhabdomyolysis is unknown. Rhabdomyolysis should be considered in patients with legionnaires' disease who have acute renal failure.

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Labetalol, an antihypertensive agent that blocks both beta- and alpha-adrenergic receptors, was administered intravenously to 19 patients with accelerated hypertension who required rapid lowering of blood pressure. Systolic blood pressure was lowered from 209 +/- 4 to 143 +/- 2 mm Hg; diastolic blood pressure was reduced from 140 +/- 2 to 93 +/- 2 mm Hg. Side-effects were minimal and included nausea, epigastric burning, rhinorrhea, and premature ventricular contractions. One patient became hypotensive and required treatment. Overall, the study demonstrates labetalol to be a safe and effective agent for the emergency lowering of blood pressure, with demonstrated results comparable to other parenteral agents.

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