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PubMed1991

Acute heat exposure causes cellular alteration in cerebral cortex of young rats.

The possibility that prolonged heat exposure resulting in a failure of central thermoregulatory mechanism may induce cellular damage in brain was examined in young rats. Children exposed to Indian summer heat can develop sudden pathophysiological symptoms. Subjection of young animals to similar acute systemic heat exposure at 38 degrees C (relative humidity, 46%) for 4 h resulted in a profound hyperthermia, and behavioral stress symptoms e.g. salivation and prostration. Subsequent morphological examination of the brain tissue revealed profound cellular changes. In the cerebral cortex, dark neurons, swollen astrocytes, and expanded white and gray matter were quite frequent. At the ultrastructural level, collapse of microvessels, perivascular edema, vacuolation and damage to postsynaptic membrane was very common. Thus, profound hyperthermia can induce cellular changes by some direct or indirect (e.g. neurochemical) mechanism.

Animals↗
PubMed2005

Suppression of morphine withdrawal syndrome by interleukin-2 and its gene.

The naloxone-precipitated withdrawal syndrome in mice and rats after intrathecal injection of recombinant human interleukin-2 protein (rIL-2) or its gene was studied. The results showed that rIL-2 could significantly decrease the number of jumps in mice. In rats, rIL-2 significantly suppressed irritating, diarrhea, weight loss, abnormal posture and salivation. Tendencies towards reductions in teeth chewing and dog-shaking were also observed. Furthermore, pcDNA3-IL-2 (8 microg DNA) had a similar effect as 1x10 IU rIL-2 protein on inhibition of morphine withdrawal syndrome in mice, and the expression of rIL-2 protein in spinal cord could be detected for 6 days. These findings provided further evidence for the neuroregulatory function of an immunological molecule such as IL-2.

Animals↗
PubMed1997

Transient and intermittent oral dyskinesia appearing in a young woman ten days after neuroleptic treatment.

A 22-year-old woman was admitted to our hospital because she showed psychomotor excitement and signs of schizophrenia following psychological stress. Nine days after neuroleptic medication, she could not eat and exhibited high fever, diaphoresis, excessive salivation, and severe extrapyramidal signs with cogwheel rigidity and resting tremor of the upper extremities. The next day, bucco-linguomasticatory dyskinesia, which is quite similar to tardive dyskinesia, appeared. The dyskinesia lasted intermittently for 6 days. The present case shows that buccolingual dyskinesia can occur even after early neuroleptic exposure in certain patients.

Adult↗
PubMedDate not supplied

Transdermal administration of piribedil reverses MPTP-induced motor deficits in the common marmoset.

The ability of transdermal administration of the dopamine D2/D3 agonist piribedil (1-[3,4-methylenedioxybenzyl)]-4-[(2-pyrimidinyl)]piperazine) to reverse hypokinesia and other motor deficits observed in MPTP-treated common marmosets was investigated. Piribedil (2.5-10.0 mg/animal), applied directly to the skin of the abdomen as a paste, produced a long-lasting and concentration-dependent reversal of motor deficits. The antiparkinsonian actions of piribedil occurred within 10 minutes of drug administration and lasted as long as 10 hours. Transdermally applied piribedil produced a pattern of locomotor activity characteristic of normal motor behavior in this species. Symptoms of nausea (marked excessive salivation, retching, and/or vomiting) were not observed after transdermal application of piribedil. Additionally, pretreatment with the peripheral dopamine antagonist domperidone enhanced the antiparkinsonian effects of piribedil. Application to the skin of monolayer or bilayer patches impregnated with piribedil also produced a marked increase in locomotor activity and reversal of motor deficits. After application of various patch fractions (whole, one-half, or one-fourth), the increase in locomotor activity and reversal of disability correlated well with the surface area of skin covered. Measurement of serum levels of piribedil after single application of bilayer patches showed a positive relationship between drug levels and antiparkinsonian activity. Repeated daily application of piribedil bilayer patches for 5 days to MPTP-treated common marmosets primed to show dyskinesia by previous exposure to L-Dopa produced antiparkinsonian activity accompanied by dyskinetic movements. Transdermal administration of dopamine agonists such as piribedil may provide a useful means of producing a long-lasting reversal of motor deficits in Parkinson's disease while avoiding acute adverse effects such as nausea.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2002

Serotonin syndrome presenting as hypotonic coma and apnea: potentially fatal complications of selective serotonin receptor inhibitor therapy.

OBJECTIVE: To describe a patient who developed serotonin syndrome on four separate occasions as a result of monotherapy with two different selective serotonin receptor inhibitors (fluoxetine and cetalopram). DESIGN: Case report. SETTING: Community hospital. PATIENTS: Single patient with four episodes of serotonin syndrome. MEASUREMENTS AND MAIN RESULTS: The syndrome was characterized by coma/unresponsiveness (four episodes), dilated pupils (four episodes), salivation (two episodes), dryness of mouth (two episodes), myoclonus like activity of eyelids (four episodes), oculogyric crisis (four episodes), flaccid paralysis of all extremities (four episodes), tremors (two episodes), apnea (two episodes), restlessness (one episode). Recovery occurred within 24 hrs, although muscle pain and weakness persisted for 2 months after stopping fluoxetine. Apnea occurred in both episodes associated with fluoxetine therapy. CONCLUSION: Apnea and coma may occur in serotonin syndrome.

Adult↗
PubMed1995

Randomized, double-blind, controlled trial of risperidone versus clozapine in patients with chronic schizophrenia.

This study compares the antipsychotic efficacy and the tolerability of risperidone and clozapine in patients with schizophrenia. Patients were randomized to double-blind treatment with risperidone, 4 mg (N = 20), risperidone, 8 mg (N = 19), or clozapine, 400 mg (N = 20), daily for 28 days. Efficacy was assessed by improvement of psychotic symptoms, measured on the Brief Psychiatric Rating Scale, and Clinical Global Impression. The tolerability was assessed by the Simpson and Angus scale for extrapyramidal side effects (EPS), the Association for Methodology and Documentation in Psychiatry (AMDP) scale for somatic side effects, spontaneous reports of adverse events, clinical laboratory assessments, and vital signs. All treatments reduced psychotic symptoms. The global tolerability was significantly better in the risperidone than in the clozapine-treated patients (p < 0.01). There were no differences between treatments on the AMDP scale. The most frequent spontaneously reported adverse effects were dizziness, fatigue, accommodation disturbance, and EPS in all treatment groups and increased salivation, mainly in the clozapine-treated patients. Although there were no changes in vital signs during risperidone treatment, clozapine was associated with a mean reduction in heart rate of 10 beats/minute. Risperidone tolerability at endpoint was classified as "very good" by 60 and 47% of patients treated with risperidone, 4 and 8 mg daily, respectively; the corresponding figure in clozapine-treated patients was 30%. The results suggest that risperidone is at least as effective as an antipsychotic as clozapine, providing a valuable new approach for the treatment of schizophrenia.

Adult↗
PubMed2000

Anticholinergic differences among patients receiving standard clinical doses of olanzapine or clozapine.

This study evaluated anticholinergic effects among patients with schizophrenia, schizoaffective disorder, or bipolar I disorder who were receiving either olanzapine (N = 12) or clozapine (N = 12) at standard clinical doses in a naturalistic setting. Serum anticholinergic levels were determined in adult male and female subjects using a radioreceptor binding assay. The Udvalg for Kliniske Undersogelser Scale was used to evaluate anticholinergic side effects clinically, and the Mini-Mental State Examination provided a global cognitive measure. Patients had achieved target doses that were stable at the time at which blood samples were obtained, and no other concomitant medicine with known anticholinergic potential was allowed. Patients receiving olanzapine (average dose, 15 mg/day) had serum anticholinergic levels of 0.96 (+/-0.55) pmol/ atropine equivalents compared with levels of 5.47 (+/-3.33) pmol/atropine equivalents for those receiving clozapine (average dose, 444 mg/day) (p < 0.001). Rates of increased and decreased salivation were significantly more common among the clozapine- and olanzapine-treated patients, respectively, whereas constipation, urinary disturbances, and tachycardia/palpitations were significantly more common among clozapine-treated patients. Neither group showed any global cognitive deficits. Olanzapine-treated patients had serum anticholinergic levels that were less than one fifth those of the clozapine-treated patients. Furthermore, clinical evaluations confirmed that clozapine-treated patients experienced more frequent and severe anticholinergic side effects (except dry mouth). However, none of the patients in either group expressed any desire to discontinue these medications as a result of the anticholinergic side effects.

Adult↗
PubMed1986

Esophageal acid clearance.

Esophageal acid clearance is an important defense against the development of reflux esophagitis. Acid clearance normally occurs in two sequential steps. One or two peristaltic sequences empty virtually all acid volume from the esophagus, leaving a minimal residual that sustains a low pH, and then the residual acid is neutralized by swallowed saliva. The ability of saliva to neutralize acid is primarily due to bicarbonate. Saliva flow normally increases concurrent with the onset of heartburn. Hypersalivation with heartburn, commonly referred to as waterbrash, may be a protective response to gastroesophageal reflux. Gastroesophageal reflux and esophageal acid clearance normally do not occur during sleep. Acid clearance may be delayed markedly in the event that a subject falls asleep before clearance of acid from the esophagus is complete. Esophageal acid clearance may be prolonged by abnormal esophageal emptying or impaired salivation in patients with gastroesophageal reflux disease.

Deglutition↗
PubMed1997

Trihexyphenidyl treatment of clozapine-induced hypersalivation.

The objective of this study was to investigate the efficacy of the anticholinergic agent trihexyphenidyl in the treatment of clozapine-induced hypersalivation. Fourteen chronic schizophrenic patients who exhibited nocturnal hypersalivation during clozapine treatment were coadministered trihexyphenidyl (5-15 mg/day, at bedtime) for 15 days. Salivation was assessed by a single-item 5-point scale. A reduction of 44% in the reported nocturnal hypersalivation was observed after trihexyphenidyl treatment. These results indicate that at least some chronic schizophrenic patients with clozapine-induced nocturnal hypersalivation may benefit from anticholinergic treatment.

Adult↗
PubMed2000

Potential use of ipatropium bromide for the treatment of clozapine-induced hypersalivation: a preliminary report.

Sialorrhea is reported by 31% of patients taking clozapine. Anticholinergic agents and adrenergic agonists are used for its treatment based on empirical evidence. In the present study, 10 patients who failed to respond to anticholinergic or adrenergic agents received intranasal ipatropium bromide (IPB) to minimize anticholinergic systemic absorption. Intranasal IPB was given to 10 patients for clozapine-induced sialorrhea who failed to respond to benztropine or clonidine. Pre-, post- and 6 month follow-up values were recorded on a single-item, 5-point Hypersalivation Rating Scale. The sign test was used for statistical comparison (P < 0.05). Eight patient reported initial improvement in sialorrhea values. Two patients reported no change and two patients discontinued IPB. At 6 months, six patients maintained improvement. Side-effects for IPB were minor. A significant trend was observed in the values pre- and post-treatment with IPB (P < 0.004). Improvement was maintained at 6 month follow-up (P < 0.008). This case series demonstrates the possible utility of intranasal IPB for clozapine-induced sialorrhea. Intranasal IPB lacks significant systemic anticholinergic effects when prescribed along with clozapine. This study shows only qualitative differences in salivation values and large controlled-comparative trials are needed.

Adult↗
PubMed2001

Ketamine sedation for pediatric gastroenterology procedures.

BACKGROUND: Although the dissociative sedative ketamine is used commonly for pediatric procedural sedation in other settings, the safety of this agent in pediatric gastroenterology is not well-studied. A 5-year experience with ketamine sedation for pediatric gastroenterology procedures was reviewed to document the safety profile of this agent and to identify predictors of laryngospasm during esophagogastroduodenoscopy (EGD). METHODS: The study was a retrospective consecutive case series of children receiving ketamine administered by pediatric gastroenterologists skilled in basic airway management to facilitate pediatric gastrointestinal procedures during a 5-year period. Patient's records were reviewed to determine indication, dosage, adverse effects, drugs, inadequate sedation, and recovery time for each sedation. A multiple logistic regression analysis was performed to identify predictors of laryngospasm during EGD. Outcome measures were descriptive features of sedation, including adverse effects and predictors of laryngospasm during EGD. RESULTS: During the study period pediatric gastroenterologists administered ketamine 636 times, primarily for EGD (86%) and primarily by the intravenous route (98%). The median loading dose and total dose were 1.00 mg/kg and 1.34 mg/kg, respectively. Inadequate sedation was noted in seven (1.1%) procedures. Adverse effects included transient laryngospasm (8.2%), emesis (4.1%), recovery agitation (2.4%), partial airway obstruction (1.3%), apnea and respiratory depression (0.5%), and excessive salivation (0.3%). There were no adverse outcomes attributable to ketamine. Nearly half (46%) the subjects had severe underlying illness (American Society of Anesthesiologists (ASA] class > or =3). All instances of laryngospasm occurred during EGD (9.5% incidence), and the only independent predictor of laryngospasm in this sample was decreasing age. The incidence of laryngospasm was 13.9% in preschool-aged (< or =6 years) children and was 3.6% in school-aged (>6 years) children (difference 10.3%, 95% confidence intervals 5.5-14.9%). No dose relationship was noted with laryngospasm, and the risk did not increase with underlying illness. CONCLUSION: Pediatric gastroenterologists skilled in ketamine administration and basic airway management can effectively administer this drug to facilitate gastrointestinal procedures. Transient laryngospasm occurred in 9.5% of children receiving ketamine for EGD, and its incidence was greater in preschool than in school-aged children.

Adolescent↗
PubMed1989

Carbamate and organophosphate poisoning in early childhood.

Twenty-five infants and young children intoxicated by carbamate and organophosphorus compounds are described. Presenting signs and symptoms in children differed from those described in adults and were mainly related to severe CNS depression, coma and stupor, dyspnea, and flaccidity. Other clinical signs such as miosis, excessive salivation and tearing, sweaty, cold skin, and gastrointestinal symptoms were less frequent, while fasciculations and bradycardia were quite uncommon on arrival. Only two patients presented with all typical signs of organophosphate poisoning as described in adults. Signs of carbamate poisoning were indistinguishable from those of organophosphate poisoning and included signs of myoneural and CNS cholinergic receptor involvement, in addition to parasympathetic muscarinic dysfunction. Atropine sulfate was found to have a clear beneficial CNS effect in addition to its known peripheral antimuscarinic effect. Our data suggest that the clinical presentation of carbamate and organophosphate poisoning in early childhood and its response to therapy are quite different from those of adults and older children.

Atropine↗
PubMed2001

Ketamine sedation for pediatric critical care procedures.

OBJECTIVES: To describe our experience using ketamine sedation to facilitate pediatric critical care procedures, and to document the safety profile of ketamine in this setting. DESIGN: Retrospective consecutive case series. SETTING: Pediatric intensive care unit of a tertiary children's hospital. PATIENTS: Children receiving ketamine for procedural sedation over a 5-year period. INTERVENTIONS: We reviewed patient records to determine indication, dosing, adverse events, inadequate sedation, and recovery time for each sedation. OUTCOME MEASURES: Descriptive features of sedation including adverse events. RESULTS: During the study period, children in our pediatric intensive care unit received ketamine at total of 442 times to facilitate a wide variety of critical care procedures, most commonly central line placement, esophagogastroduodenoscopy, and wound debridement. Most study children had substantial underlying illness (ASA > or = 3 in 88%; ASA > or = 4 in 39%). Inadequate sedation was noted in only nine (2%) procedures. Adverse effects included transient laryngospasm (n = 9), transient partial airway obstruction (n = 5), apnea with bradycardia (n = 1), emesis during the procedure (n = 2), emesis during recovery (n = 9), mild recovery agitation (n = 10), moderate-to-severe recovery agitation (n = 1), and excessive salivation (n = 4). There were no adverse outcomes attributable to ketamine. CONCLUSION: Pediatric intensivists skilled in ketamine administration can safely and effectively administer this drug to facilitate critical care procedures. Despite the ill nature of our patient sample, adverse effects were uncommon.

Adolescent↗
PubMed2004

Clozapine treatment of adolescents with posttraumatic stress disorder and psychotic symptoms.

This study investigates the efficacy of clozapine in treatment-resistant abused adolescents detained in a secure environment who present with chronic posttraumatic stress disorder and psychotic symptoms. All participants had received at least 2 trials of conventional neuroleptic medication prior to starting clozapine. Efficacy was assessed by using single case methodology across 6 participants employing predependent and postdependent measures of psychiatric symptoms and behavioral observations. Subjective self-reports were also sought after treatment had been established. Evaluation of the data suggests that 4 of the participants demonstrated substantial improvements in psychiatric symptoms and behavioral presentation once a therapeutic dose of clozapine had been achieved. Questionnaire responses from 5 participants indicated that clozapine treatment was associated with a reduction in hallucinatory experiences. The most troubling side effects were those of excessive salivation, dizziness, and weight gain. These findings indicate that clozapine may be effective in decreasing psychiatric symptoms and risk behaviors in traumatized adolescents presenting with psychotic symptoms.

Adolescent↗
PubMed2004

The morbidity of buccal mucosal graft harvest for urethroplasty and the effect of nonclosure of the graft harvest site on postoperative pain.

PURPOSE: We assess the medium and long-term morbidity of buccal mucosal graft (BMG) harvest for urethroplasty, and evaluate the effect of nonclosure of the graft harvest site on postoperative pain. MATERIALS AND METHODS: A questionnaire was mailed to 110 men who underwent BMG urethroplasty between January 1, 1997 and August 31, 2002. Demographic data and side effects of BMG harvest, including oral pain, sensation and intake, were assessed postoperatively. A prospective study was then performed to compare 20 unselected men whose BMG donor site was closed with a group of 20 men in whom it was left open using a 5-point analog pain score that was completed twice daily for the first 5 postoperative days. RESULTS: A total of 49 men with a median age of 49 years (range 23 to 73) returned questionnaires relating to 57 BMG harvests. Of the graft harvests 47 (83%) were associated with postoperative pain, which was worse than expected in 24 (51%). Of the 57 patients 51 (90%) resumed oral liquid intake within 24 hours and 44 (77%) resumed normal diet within 1 week. Postoperative side effects included perioral numbness in 39 (68%) patients with 15 (26%) having residual numbness after 6 months, initial difficulty with mouth opening in 38 (67%) with 5 (9%) having persistent problems, changes in salivation in 6 (11%) and mucous retention cyst that required excision in 1 (2%). The men in the prospective donor site study had a median age of 51 years (range 24 to 70). Mean pain score for patients with donor site closure was 3.68 and was significantly higher than that for patients without donor site closure (2.26, p < 0.01). CONCLUSIONS: Buccal mucosal graft harvest is not a pain-free procedure. Closure of the harvest donor site appears to worsen this pain and it may be best to leave harvest sites open. The main long-term complications are perioral numbness, persistent difficulty with mouth opening and change in salivary function.

Adult↗
PubMed2004

Demonstration of bladder selective muscarinic receptor binding by intravesical oxybutynin to treat overactive bladder.

PURPOSE: The current study was done to elucidate the in vivo mechanism of action of intravesical instillation of oxybutynin to treat overactive bladder. MATERIALS AND METHODS: In rats receiving oral and intravesical oxybutynin we measured muscarinic receptors in the bladder and other tissues by radioligand binding assay using [3H]NMS ([N-methyl-3H] scopolamine methyl chloride) with the simultaneous measurement of plasma concentrations of oxybutynin and its active metabolite N-desethyl-oxybutynin. Pilocarpine induced salivary secretion was also measured. RESULTS: Following oral administration of oxybutynin there was a significant increase in the apparent dissociation constant (Kd) for specific [3H]NMS binding in the bladder, submaxillary gland, heart and colon of rats at 1 and 3 hours with a consistent decrease in the maximal number of binding sites (Bmax) in the submaxillary gland. Furthermore, a marked and prolonged decrease in pilocarpine induced salivary secretion in rats was observed by oral oxybutynin. In contrast, intravesical instillation of oxybutynin produced a significant increase in Kd for specific [3H]NMS binding in the bladder of rats at 0.5 to 4 hours later and also in the submaxillary gland only at 0.5 hours later. The enhancement in Kd was much larger and longer lasting in the bladder than in the submaxillary gland. Moreover, intravesical oxybutynin had little muscarinic receptor binding activity in the heart and colon, and little significant suppression of pilocarpine induced salivation in rats. The plasma concentrations of oxybutynin and N-desethyl-oxybutynin were much higher in rats receiving oxybutynin orally than intravesically. CONCLUSIONS: Intravesical oxybutynin in rats may cause selective binding of bladder muscarinic receptors via a direct local effect, while oral oxybutynin may exert predominant binding of salivary gland receptors.

Administration, Intravesical↗
PubMed2004

Update on botulinum toxin use in facial plastic and head and neck surgery.

PURPOSE OF REVIEW: The purpose of this review is to discuss current trends in the medicinal use of botulinum toxin in head and neck and facial plastic surgery. The basic science of botulinum toxin is presented along with a comparison of the subtypes currently available on the market. Site-specific applications of botulinum toxin in the head and neck region are presented. RECENT FINDINGS: The use of botulinum toxin continues to expand, both in volume and in number of applications. The main application of botulinum toxin in facial plastic surgery is in the effacement of dynamic or hyperkinetic facial lines. The granting of US Food and Drug Administration approval for the use of Botulinum Toxin type A in the treatment of glabella lines marks a major milestone for the more widespread usage of this product in cosmetic settings. Additional cosmetic applications include crow's feet, marionette lines, and platysma banding. Noncosmetic applications in the head and neck include dystonias (including torticollis), facial and generalized muscle spasms, migraine headaches, hyperhidrosis, spasmodic dysphonia, sialorrhea, gustatory sweating, and involuntary movement disorders. SUMMARY: The use of botulinum toxin in the treatment of hyperkinetic conditions and disorders of excessive salivation is well established and enjoys an excellent safety profile. The cosmetic use of botulinum toxin continues to expand. The chronic use of botulinum toxin specifically for cosmetic purposes is worthy of additional study.

Botulinum Toxins↗
PubMed2006

A review of the surgical and medical treatment of Frey syndrome.

Frey syndrome represents a fascinating example of how nerve regeneration can go awry. The syndrome is characterized by profuse facial sweating and flushing that occurs when salivation is stimulated. It can develop following a variety of insults but is most commonly encountered as a complication of parotidectomy. Consequently, it is mainly head and neck surgeons who see and treat this disorder; however, it is important for other clinicians to recognize what these unusual symptoms represent. Diagnosis may be based either on clinical presentation or through objective testing methods. Potential negative social and psychologic implications of this condition can be significant, and treatment ranging from topical agents to local injections of botulinum toxin (Botox) to surgical intervention should be offered to patients. In this article, we present an up-to-date review of the surgical and medical treatment of this syndrome.

Drug Therapy↗