Transient chemotherapy-induced alopecia after successful reversal of 5-fluorouracil myelosuppression and neurotoxicosis in a 9-month-old dog.

BACKGROUND: 5-Fluorouracil (5-FU) cream is a common human topical chemotherapy agent with potentially fatal neurotoxic effects on dogs if accidentally ingested. There are seldom reports in veterinary literature describing the successful outcome of intervention after accidental ingestion of 5-FU cream. CASE SUMMARY: A 9-month-old spayed female labradoodle presented 14 h after ingesting an unknown amount of 40 g tube of Efudex cream (5% 5-FU). The dog presented in status epilepticus, which was managed with benzodiazepines and levetiracetam in conjunction with induced coma and mechanical ventilation. No further seizure activity occurred throughout the ensuing 5 days of hospitalisation; however, myelosuppression was featured. The dog was discharged home after 5 days of hospitalisation. Three days post discharge, the dog was noted to develop focal alopecia around the eyes and temporal region. 14 days after discharge, the alopecia progressed to a majority of the head and body. CONCLUSION: To the authors' knowledge, this is the first report that documents the enduring adverse effects of 5-FU cream after survival of the initial episode, including an earlier onset of myelosuppression and diffuse alopecia. Successful treatment of accidental 5-FU ingestion is possible several hours after the initial event with minimal long-term consequences.

Coherin: a new peptide of the bovine neurohypophysis with activity on gastrointestinal motility.

A factor with potent activity in the regulation of mammalian gastrointestinal motor function has been isolated from the bovine posterior pituitary gland by a process allowing minimal dissociation of neurophysin-bound complexes and the separation of free unbound peptides. This substance alters the frequency, amplitude, rhythm, and duration of peristaltic contraction.

Auditory brain-stem potentials with unilateral pontine hemorrhage.

Although there have been extensive anatomical and physiological studies in animals, the actual neural sources, or even the laterality, of some components of auditory brain-stem evoked potentials in humans are uncertain. We studied these responses in a 56-year-old patient who had a clearly demarcated pontine hemorrhage on the right side. The patient was somnolent, with dense left hemiplegia and signs of involvement of right cranial nerves V, VI, and VII. Stimulation of the left ear (ie, contralateral to the lesion) evoked a normal series of waves with clearly resolved positive components peaking at 2.0, 3.3, 4.8 (wave IV), and 6.0 ms (wave V). Stimulation of the right ear (ie, ipsilateral to the lesion) evoked only waves I, III, and IV. These results suggest that a pathway ipsilateral to the stimulated ear is necessary and sufficient for generation of auditory wave V and that wave IV is generated in bilateral pathways.

Peptide treatment of postgastrectomy obstruction.

Seventeen patients with symptoms of acute or chronic postgastrectomy obstruction of a life-threatening nature have been treated with a peptide substance that is isolated from the bovine neurohypophysis (coherin) and has a regularizing effect on the electromotor performance of the small intestine of the dog and man. All patients treated in this study were relieved of their obstructive symptoms. After weight gain began, the majority of patients with acute obstruction were able to discontinue coherin therapy. Five patients with chronic obstruction have required prolonged treatment with coherin to maintain normal alimentary function.

Lesion-produced telencephalic catecholamine imbalances and altered operant pecking rates in pigeons.

Pigeons with bilateral neurotoxic or electrolytic lesions within ventral mesencephalon, in nucleus tegmenti pedunculo pontinus (TP) (equivalent to substantia nigra) or area ventralis of Tsai (AVT), were found to have catecholamine (CA) depletion in the telencephalon, including the paleostriatum augmentatum (PA) and lobus parolfactorius (LPO), avian basal ganglia rich in CA. Joint telencephalic concentrations of dopamine (DA) and norepinephrine (NE) within individuals were found to vary with sustained fixed interval (FI) pecking rate increases or decreases following surgery. Low (below 75% of controls) DA/normal NE concentrations were found in individuals showing a marked reduction in their key pecking rates; low DA/low NE concentrations were found in individuals showing a marked increase in their pecking rates. The fit of these data with the NE-DA interaction hypothesis of Antelman and Caggiula [2] was acknowledged but the nature of that interaction remains to be clarified.

The physiologic properties and therapeutic potential of coherin.

Coherin, a peptide isolated from the bovine neurohypophysis, has been shown to be an effective therapeutic agent in post-gastric surgery physiologic obstruction and regional ileitis. Of twenty-four patients with post-gastric surgery physiologic obstruction, coherin relieved symptoms in twenty-three, a 96 per cent efficacy rate. The efficacy of coherin with ileitis was based on the fact that ten of twenty-seven patients treated have required coherin on a continuing basis to stay functional. These patients have requested coherin treatment for an average of five years each, and have each on multiple occasions tried to discontinue coherin treatment with prompt return of symptoms and cessation of symptoms when coherin was reinstituted. All of the ileitis patients had previously failed to respond to standard and usual medical treatment.

Amphetamine and apomorphine induced stereotyped behavior in adult pigeons.

Induced pecking by apomorphine has been reported in the past in pigeons. Research has supported the view that its mechanisms are, at least in part, dopaminergic in nature. This study tested the ability of amphetamine to induce stereotyped pecking. Amphetamine was found effective within a narrow dose range, displaying a relatively low potency for stereotyped pecking and high toxicity compared with apomorphine. The latter drug produced appreciable pecking rates that were proportional to dose over a wide range. The description of other stereotyped responses of the head and mouth, including swallowing, mandibulating and head shaking, which are produced by both of these drugs, supports the idea that common neural mechanisms are involved. It was suggested that the qualitative and quantitative measures afforded by pecking and non-pecking stereotyped behavior in the pigeon make this a useful animal model for the study of the mechanisms of stereotyped behavior.

Dopaminergic nature of feeding-induced behavioral stereotypies in stressed pigeons.

Dopamine dependence of feeding-induced behavioral stereotypies (FIBS) was demonstrated by FIBS facilitation following chronic treatment with a dopamine (DA) agonist, apomorphine, and by FIBS inhibition following the administration of haloperidol, a DA antagonist. However, individuals that emitted FIBS were differentiated from those not emitting FIBS not by assayed telencephalic DA concentrations alone but by a higher stereotyping index (SI), a score positively related to the ratio of telencephalic DA-norepinephrine (NE) concentrations. These latter findings support the hypothesis of Antelman and Caggiula [3] which indicates that a catecholamine interaction in the brain serves to facilitate or inhibit some behavioral actions associated with stress.

Corticotropin-releasing factor and defensive withdrawal: inhibition of monoamine oxidase prevents habituation to chronic stress.

There is growing evidence for a role of extrahypothalamic corticotropin-releasing factor (CRF) in the pathogenesis of anxiety. A modified form of the defensive withdrawal test was used to test the anxiogenic effects of acute administration of intracerebroventricular (1 microg, i.c.v.) CRF in adult male rats. Habituation to the mild stress of daily handling and subcutaneous (s.c.) saline injection over 2-6 weeks abolished the anxiogenic effects of exogenous CRF. At 6 weeks this habituation also resulted in attenuation of baseline withdrawal behavior. CRF receptor binding was significantly decreased in the amygdala of chronically handled animals and may have been responsible for this habituation phenomenon. Comparison of rats treated with the monoamine oxidase (MAO) inhibitor, phenelzine [3 mg/kg, s.c., daily for 2-6 weeks] to the saline-treated groups revealed a failure to habituate to the chronic handling, as the baseline withdrawal (after injection of artificial CSF) by the phenelzine-treated animals was not different from the baseline withdrawal by unhandled rats. In comparison to rats treated chronically with saline, phenelzine treatment enhanced the anxiogenic effect of CRF. In summary, habituation to a mild chronic stress decreased baseline defensive withdrawal. Intraventricular administration of CRF produced an anxiogenic response as measured in the defensive withdrawal test, which was lost through exposure to mild chronic stress. Two or 6 weeks of daily handling and SC saline injection caused a downregulation of CRF receptors in the amygdala, which could account for the behavioral habituation and the loss of CRF-induced defensive withdrawal. Phenelzine treatment concurrent with mild chronic stress prevented habituation and maintained the anxiogenic effect of CRF in spite of the downregulation of CRF receptors in the amygdala.

Switching from oral cholinesterase inhibitors to the rivastigmine transdermal patch.

Oral cholinesterase inhibitors (ChEIs) are associated with side effects such as nausea and vomiting. The use of transdermal patches for ChEI delivery may help to minimize these problems. The objective of this review was to consider available data from patients switching from oral ChEIs to transdermal rivastigmine treatment, and to suggest practical guidelines for patients wishing to do this. Literature database and reference list searches were performed to identify suitable publications. Data from two clinical trials and a series of open observational studies, in which patients were switched to the rivastigmine patch from oral rivastigmine, donepezil tablets, or galantamine, were evaluated. Adverse events were tabulated. In the studies reported here, nausea was reported in up to 3.2% and vomiting in up to 1.9% of patients switching to the rivastigmine patch from oral rivastigmine. Similar rates (up to 3.8% of patients for nausea and 0.8% of patients for vomiting) were reported when switching to the rivastigmine patch from donepezil tablets, and no nausea or vomiting was reported in a case study of patients switching to the rivastigmine patch from galantamine tablets. Switching regimes used in clinical trials appeared well tolerated. Data support recommendations for patients on high rivastigmine capsule doses to switch directly to the 9.5 mg/24 h rivastigmine patch, while those on lower oral rivastigmine doses should start on the 4.6 mg/24 h patch for 4 weeks before increasing to the 9.5 mg/24 h patch. This latter regimen is recommended for patients on other oral cholinesterase inhibitors if switching is medically indicated or requested by the patient or the caregiver.