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Biomedical subjects

F Adams

Publications and source records attributed to F Adams.

At least 19 recordsLinked to original sources

Effects of substance P on extracellular dopamine in neostriatum and nucleus accumbens.

Microdialysis was used to monitor changes in dopamine release in the neostriatum and nucleus accumbens after peripheral administration of substance P in freely moving rats. Substance P in a dose of 50 micrograms/kg produced a steady moderate increase in dopamine levels in the neostriatum, which persisted for at least 5 h. In contrast, a dose of 250 micrograms/kg caused an acute increase in dopamine levels in the nucleus accumbens, which lasted about 2 h. These data suggest that the peripheral administration of substance P can influence dopamine release in mesolimbic and mesostriatal terminals.

3,4-Dihydroxyphenylacetic Acid

Lateralized changes in behavior and striatal dopamine release following unilateral tactile stimulation of the perioral region: a microdialysis study.

Intracranial microdialysis was used to measure dopamine (DA) release in the ventrolateral neostriatum of freely moving rats before and after unilateral tactile stimulation was applied to the orofacial region. Several behavioral parameters which have been linked to changes in nigrostriatal DA transmission (scanning, or snout contact with the walls of the observation chamber, turning and locomotion) were measured as well. Orofacial stimulation was followed by an asymmetrical increase in DA release with concentrations of transmitter higher in the neostriatum ipsilateral to the side of stimulation. Asymmetrical scanning behavior was observed during the time period when DA release was asymmetric, with rats favoring use of the side of the face contralateral to increased DA release. Increases in the DA metabolites DOPAC and HVA were found in the striatum ipsilateral to stimulation, but were delayed 40 min following the increase in DA.

Animals

On the use of laser microprobe mass spectrometry for the analysis of organic biomolecules.

Laser microprobe mass spectrometry has been applied to a variety of organic polyfunctional molecules, covering a wide range of polarity and mass spectrometric behaviour. The technique apparently combines desorption under relatively soft conditions with extensive fragmentation and hence allows much structural information from intactly released thermolabiles to be obtained. The mass spectra appear unfamiliar in comparison to conventional techniques. Interpretation is attempted in a purely empirical way by means of the evidence from our database and tentative hypotheses to rationalize the desorption and ionization by laser microbeam irradiation of organic solids. Selected examples are presented to illustrate the potential and limitations of the method in the field of biomolecules, such as pyridoxine and pyridoxal phosphate, nucleosides, nucleotides and related analogues, drugs and the corresponding N-oxides.

Flunarizine

Speciation of ionic alkyllead in potable water and soil.

Various potable water and soil samples have been analyzed for tri- and dialkyllead compounds using a sensitive speciation procedure based on diethyldithiocarbamate extraction, Grignard derivatization and gas chromatography-atomic absorption spectrometry. The species are generally present as ultra-trace contaminants, and their abundance is critically discussed. In addition, a degradation study of ionic alkyllead in ambient matrices is presented.

Gas Chromatography-Mass Spectrometry

Focal subdermal toxicity with subcutaneous opioid infusion in patients with cancer pain.

Few significant side effects have been reported from the treatment of cancer pain by subcutaneous infusion of opioids. In this prospective year-long study, 8 of 13 patients treated by this technique experienced painful chronic focal toxicity, manifested by induration, erythema and subdermal necrosis during subcutaneous analgesia therapy. A hydraulic-irritation effect is suggested.

Adult

Interferon-induced organic mental disorders associated with unsuspected pre-existing neurologic abnormalities.

Eleven patients ranging in age from 52 to 80 years, undergoing treatment for cancer with various preparations of interferon received neurobehavioral evaluations after experiencing unexpectedly severe organic mental disorders. The reactions ranged from delirium to extrapyramidal symptoms, mania, and neurasthenia with catatonic episodes. Computed tomographic (CT) scans of the brain disclosed unsuspected pre-existing neurologic abnormalities in all patients, including cerebral atrophy (6/11), brain metastases (4/11), and evidence of head injury incurred 40 years earlier (1/11). These findings suggest that cancer patients with pre-existing neurologic dysfunctions are at increased risk for severe interferon neurotoxicity.

Aged

Intraventricular microdialysis: a new method for determining monoamine metabolite concentrations in the cerebrospinal fluid of freely moving rats.

A new method is described to estimate the cerebrospinal fluid (CSF) concentrations of monoamine metabolites (dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA] in the lateral ventricle of freely moving rats by use of in vivo microdialysis. Both the baseline concentrations of these metabolites and the rate of dopamine (DA) turnover (estimated by the accumulation of total DA metabolites after 200 mg/kg probenecid) were within the range reported when other methods were used to sample CSF. A series of preliminary studies were conducted to demonstrate that this method can be used to repeatedly sample CSF, and to show that the method is sensitive to local changes in dopaminergic activity induced by lesions, drugs or grafts. (1) Unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra produced a significant decrease in the CSF concentrations of DOPAC and HVA ipsilateral to the lesion, relative to the contralateral side or to concentrations in animals without lesions. (2) When left and right lateral ventricles were sampled simultaneously in animals with a unilateral 6-OHDA lesion, haloperidol induced an increase in DOPAC and HVA concentrations in CSF on both sides of the brain. Interestingly, the haloperidol-induced increase in CSF concentrations of DA metabolites was greater adjacent to the intact striatum of rats with unilateral 6-OHDA lesions than in animals with no lesion. (3) Finally, in animals with adrenal medulla tissue grafted into the lateral ventricle there was an increase in the CSF concentration of DOPAC compared to pregraft values or to those of animals with control grafts.

3,4-Dihydroxyphenylacetic Acid

Emergency intravenous sedation of the delirious, medically ill patient.

More than 2,000 medically ill patients with delirium have been treated by intravenous administration of a combination of haloperidol and lorazepam. The protocol was developed over 8 years at two major cancer centers in the United States and Canada. The addition of the potent benzodiazepine to the neuroleptic produces rapid and safe symptomatic sedation in emergency conditions and allows the use of lower doses of haloperidol. The combination was first attempted when doses of haloperidol as high as 350 mg failed to provide rapid emergency neurobehavioral control. All patients treated to date had cancer, and all were suffering multisystem organ failure. Hourly doses of each drug as high as 10 mg for as long as 15 days have been shown to be safe and effective in the most critically ill patient with delirium. Patients generally respond to the first one or two doses and, in most cases, less than 100 mg/day of each drug is required. The addition of the opioid hydromorphone makes the combination ideal for the treatment of intractable pain in terminally ill cancer patients. This polypharmacological approach is advocated as the method of choice for emergency sedation of the delirious patient as well as for palliative care.

Critical Care

Treatment of severe, refractory agitation with a haloperidol drip.

A case of agitated delirium secondary to bilateral occipital cerebral infarctions in a cancer patient was refractory to trials of large doses of intravenous psychotropic agents, but continuous intravenous infusion of haloperidol controlled agitation rapidly and safely. A total haloperidol dose of 600 mg/day was used without complications. Haloperidol by continuous infusion should be considered in the management of severe, refractory agitation in patients who are medically ill.

Acute Disease

Phase I trial of caracemide using bolus and infusion schedules.

We conducted a phase I trial of caracemide, a new chemotherapeutic agent, which is active in the MX1 (mammary) and CX1 (colon) human tumor xenografts. Using a 5-day bolus schedule, dose-limiting toxicity consisting of burning perioral pain associated with flushing, nasal stuffiness, and excess lacrimation was seen at 650 mg/m2/day. Using a 5-day continuous-infusion schedule, dose-limiting toxicity in the form of changes in affect, lethargy, disorientation, and cognitive dysfunction with electroencephalogram abnormalities was noted at 800 mg/m2/day. The recommended phase II dose levels are 525 mg/m2/day using the 5-day bolus schedule and 650 mg/m2/day using the continuous-infusion schedule. Because of venous pain at the site of infusion, the drug must be delivered via central venous access. The pathophysiology of both the peripheral and central side effects of caracemide may be related to increased cholinergic activity.

Adult

Analgesic effect of alprazolam in patients with chronic, organic pain of malignant origin.

Effective analgesia is a crucial factor in promoting quality of life for cancer patients. While undergoing treatment with the minor tranquilizer alprazolam for a coincidental psychiatric disturbance, 39 patients with malignancies and an associated causalgic pain syndrome had a marked analgesic response. Diagnostic and treatment guidelines for organic pain syndromes are reviewed, as are indications for the use of anticonvulsants and benzodiazepines as analgesic adjuvants. The results of this study suggest that the use of benzodiazepines for patients with this refractory pain syndrome should be evaluated further.

Adjustment Disorders