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PubMed1996

Human brainstem preganglionic parasympathetic neurons localized by markers for nitric oxide synthesis.

Identification of human parasympathetic preganglionic neurons in pontomedullary regions has been largely based on studies using cholinesterase histochemical procedures, and so far there is no adequate account of the location of these cells. Nitric oxide synthase (NOS) is present in brainstem parasympathetic preganglionic salivatory neurons in the rabbit (Zhu et al., 1996). In the present study we have used histochemical and immunohistochemical staining for NOS to examine possible preganglionic parasympathetic neurons in the human brainstem. We examined, in five human brains, the distribution, through the caudal pons and rostral medulla, of NOS-positive neurons in serial sections stained with NADPH diaphorase for histochemistry, and with antibodies against neuronal NOS peptide for immunohistochemistry. In scattered pontomedullary regions (rostral to the dorsal motor nucleus and the nucleus ambiguus) known to contain parasympathetic preganglionic neurons in animals, we observed groups of NOS-positive neurons which correspond in morphology and distribution with NOS-positive parasympathetic preganglionic neurons in rabbits. These neurons are probably parasympathetic preganglionic neurons in the human brainstem, involved in the control of lacrimation, salivation, oral and nasopharyngeal secretion, as well as the control of the dilation of extra- and intracranial blood vessels.

Aged↗

PubMed2001

Oral appliances for the management of severe snoring: a randomized controlled trial.

The aim of this randomized controlled trial was to assess the effectiveness of a mandibular advancement appliance (MAA) in managing severe snoring. Twenty-eight adults with severe snoring and normal overnight oximetry were recruited from sleep disorder clinics. A maxillary placebo appliance and a MAA were worn by each subject for a period of 4-6 weeks each. Questionnaires at baseline and after each appliance period assessed bed partners' reports of snoring severity (loudness and number of nights per week), and patients' records of daytime sleepiness. Twenty-five subjects completed the entire trial. The MAA was significantly more effective than the placebo in reducing the frequency and loudness of snoring, the reported daytime sleepiness and the frequency of morning tiredness. Excessive salivation was the most commonly reported complication. It was concluded that the custom-made MAA was significantly more effective than the placebo in managing the main symptoms of severe snoring. However, not all subjects' partners reported an improvement with the MAA, with 84 per cent reporting a reduction in snoring loudness and 76 per cent reporting snoring on fewer nights per week.

Adult↗

PubMed2002

Mandibular advancement appliances and obstructive sleep apnoea: a randomized clinical trial.

This randomized placebo-controlled cross-over trial assessed the effectiveness of a mandibular advancement appliance (MAA) in managing obstructive sleep apnoea (OSA). Twenty-one adults, with confirmed OSA, were provided with a maxillary placebo appliance and a MAA for 4-6 weeks each, in a randomized order. Questionnaires at baseline and after each appliance assessed bed-partners' reports of snoring severity (loudness and number of nights per week), and patients' daytime sleepiness (Epworth Sleepiness Score, ESS). The Apnoea Hypopnoea Index (AHI) and Oxygen Desaturation Index (ODI) were measured at baseline and with each appliance during single night sleep studies. Seventy-nine per cent of subjects wore their MAA for at least 4 hours at night. Sixty-eight per cent of subjects wore their MAA for 6-7 nights per week. Excessive salivation was the most commonly reported complication. One subject was unable to tolerate the MAA and withdrew from the study. Among the remaining 20 subjects, the MAA produced significantly lower AHI and ODI values than the placebo. However, although the reported frequency and loudness of snoring and the ESS values were lower with the MAA than the placebo, these differences were not statistically significant. When wearing the MAA, 35 per cent of the OSA subjects had a reduction in the pre-treatment ODI to 10 or less, while 33 per cent had an AHI of 10 or less. The MAA was less effective in the subjects with the most severe OSA (pre-treatment ODI > 50 and/or pre-treatment AHI > 50).

Adult↗

PubMedDate not supplied

Sudden death following accidental ingestion of chlormequat.

A 59-year-old white male accidentally ingested a mouthful of a plant growth chemical, Cycocel, containing 11.8% of the active ingredient (2-chloroethyl)trimethylammonium chloride (chlormequat). He was seen by a family physician and then transferred to a hospital where he died as a result of ventricular fibrillation, which progressed to asystole. Postingestion symptoms were typical of cholinergic crisis and included salivation, diaphoresis, bradycardia, visual disturbances, and seizure. Autopsy findings showed marked pulmonary edema, coronary atherosclerosis, atheromata of aorta, and localized adenocarcinoma of the prostate. Toxicological analyses of biological samples showed the presence of chlormequat in the stomach contents and urine.

Accidents, Occupational↗

PubMed1992

Multiple transmission of Plasmodium gallinaceum (Eucoccida: Plasmodiidae) during serial probing by Aedes aegypti (Diptera: Culicidae) on several hosts.

Mosquitoes salivate before ingesting blood, and sporozoites are transmitted during this phase of feeding. In the laboratory, malaria-infected Aedes aegypti were allowed to probe on a series of three chicks during a 5-min period. Probing on each host was interrupted after 10 s. Our results demonstrate that up to three hosts can be serially infected with avian malaria during a 5-min period.

Aedes↗

PubMed1993

Detection of Anaplasma marginale (Rickettsiales: Anaplasmataceae) in secretagogue-induced oral secretions of Dermacentor andersoni (Acari: Ixodidae) with the polymerase chain reaction.

The polymerase chain reaction (PCR) was used to detect Anaplasma marginale in secretagogue-induced oral secretions of male and female Dermacentor andersoni Stiles exposed as nymphs or adults by feeding on infected calves. A 409-bp DNA fragment derived from the A. marginale (Florida isolate) msp1 beta gene was amplified with oligonucleotide primers BAP-2 (5'-GTATGGCACGTAGTCTTGGGATCA-3') and AL34S (5'-CAGCAGCAGCAAGACCTTCA-3'). The target DNA was amplified in oral secretions of female ticks exposed to A. marginale as adults and stimulated to secrete by injection of dopamine. Conversely, A. marginale was detected in saliva from prefed female ticks exposed as nymphs only after stimulation with a combination of dopamine, gamma-aminobutyric acid, pilocarpine, and theophylline. Saliva from ticks exposed as nymphs and stimulated with ergot alkaloids did not contain the A. marginale target DNA. Saliva collected after 11 d of feeding from dopamine-stimulated male ticks contained A. marginale DNA. The results indicate that A. marginale is present in tick saliva and suggest that the parasite can be transmitted to cattle via saliva of feeding ixodid ticks. The variable appearance of A. marginale in saliva, regardless of the method used to induce salivation, suggests that transmission of A. marginale may be affected by the physiological state of the tick.

Anaplasma↗

PubMed1995

Depletion of total salivary gland protein in blood-fed Anopheles mosquitoes.

Reduction in total salivary gland protein from four anopheline vectors of human malaria, Anopheles stephensi Liston, An. albimanus Wiedmann, An. gambiae Giles, and An. freeborni Aitken, was quantified after mosquitoes blood-fed to repletion on human volunteers, hamsters or through a Baudruche artificial membrane. Total salivary gland protein from pools of six unfed mosquitoes ranged from 4.33 to 7.91 micrograms/ml. The difference between the total protein of glands from unfed and blood-fed mosquitoes for all species ranged from 1.77 to 3.12 (micrograms/ml for six pooled salivary glands. Total salivary gland protein for mosquitoes blood-fed to repletion was significantly less than that of unfed controls from the same cohort. Reduction in total salivary gland protein for An. freeborni and An stephensi blood fed to repletion on human volunteers, hamsters, and a Baudruche membrane ranged from 24 to 46%, from 43 to 56%, and from 24 to 51%, respectively. An. stephensi mosquitoes were allowed to blood feed on humans for 0 (unfed), 0.5-, 1.0-, 2.0-min time periods or to repletion (> 2-5 min). As feeding time increased, there was a significant decrease in total amount of protein in the salivary glands. This decrease was proportional over time, indicating that salivation occurred continuously from the beginning (probing) of blood feeding to withdrawal of the mosquito mouthparts at repletion. These data indicate that during blood feeding there difference between species in the salivary gland output measured as amount of protein depleted from the salivary glands and that depletion of salivary protein from the glands occurred continuously as mosquitoes fed to repletion.

Animals↗

PubMed1978

Arginine requirements in immature dogs.

Labrador Retriever puppies (3 kg) were fed L-amino acid (L-AA) diets, containing the equivalent of 14% protein, to determine dietary argnine requirements for optimal growth and maintenance of normal intermediary metabolism. Growth and food consumption were depressed by decreasing the dietary arginine concentration. Urinary citrate and orotate increased with decreasing dietary arginine. Elevated blood orotate, urea and NH4+-N were detected in arginine deficient dogs. More than 0.56% arginine was required to support optimum growth and prevent abnormal loss of urinary metabolites. The effect of dietary nitrogen concentration (14, 21, or 28% L-AA) on arginine requirements was examined in immature Beagles. All arginine deficient dogs and dogs fed the 28% L-AA with arginine showed signs of emesis, excessive salivation and muscle tremors. Hyperammonemia and hyperglycemia were observed 2 hours after force feeding an L-AA diet devoid of arginine. Only hyperammonemia was observed in the Labrador Retrievers fed the same diet but incorporated into a 2% agar gel. Dietary nitrogen concentration or dietary arginine content dit not significantly influence glucose tolerance response to oral glucose loading. These data show that dietary arginine is required in the immature dog and that the requirement is influenced by dietary nitrogen concentration.

Amino Acids↗

PubMed1979

Growth, appetite, sequence of pathological signs and survival following the induction of rapid, synchronous vitamin A deficiency in the rat.

Experiments were conducted to determine the sequence and reliability of appearance of key signs of vitamin A deficiency. Rapid and essentially synchronous vitamin A deficiency was induced by the withdrawal of retinoic acid from mature (190--210 g) stringently vitamin A-deficient male rats reared by feeding early growth plateau (60--70 g) vitamin A-deprived rats diets first supplemented with and then lacking in 2 micrograms retinoic acid per gram diet in repeating 18 day:10 day supplementation:deprivation cycles. Growth was depressed within 1 to 2 days of the withdrawal of retinoic aicid whether animals were force-fed or were fed ad libitum. Similar patterns were obtained when animals were fed 5 or 10 micrograms retinoic acid per gram diet. Appetite was depressed (1--2 days) whether animals were fed 18% casein diets, or were given 10% dextrose drinking solutions only. Decreased food intake was not due to impaired taste function or to poor palatability of the deficient diet. Bilateral electrolytic lesions in the ventromedial nucleus of the hypothalamus or anterior prepyriform cortex failed to prevent or to delay loss of appetite. Supplementation with antibiotics decreased body weight losses in the late stages of deficiency and increased survival time. Other signs of deficiency (days until onset following retinoate withdrawal; percent incidence) were: decreased intestinal goblet cell numbers (2--3; 80), decreased pilocarpine induced salivation (6--8; 80), tracheal metaplasia (6--8; 80), transient periocular porphyria (6--8; 60), altered salivary gland morphology (9--10; 80), decreased stomach emptying in force-fed animals (12; 70), twisting (12; 5) and leg crippling (12; 5). We conclude that the sequence of appearance of individual signs of deficiency following the induction of synchronous vitamin A deficiency is highly reproducible, and that the more general use of synchronously deficient animals would materially assist studies of cause-effect relationships in vitamin A deficiency.

Animals↗

PubMed1987

Cephalic reflexes: their role in digestion and possible roles in absorption and metabolism.

Stimulation of the oral cavity immediately elicits salivation, gastric acid secretion and pancreatic exocrine and endocrine secretions that serve to prepare the alimentary canal for digestion, transport and utilization of ingested nutrients. Oropharyngeal-stimulated responses are reliably initiated by the taste and smell of food. These gastrointestinal reflexes, often referred to as anticipatory or cephalic phase responses, are mediated by the autonomic nervous system and are believed to be independent of the postabsorptive effects of ingested nutrients. A common pathway used by cephalic phase responses to trigger gastrointestinal secretions is the vagus. Several studies have also demonstrated that cephalic stimulation activates both the sympathetic and parasympathetic nervous systems and thus, many cephalic-metabolic reflexes may arise indirectly from more general physiological changes that accompany oropharyngeal stimulation. The present studies suggest that oral stimulation results in alterations in intestinal function. Specifically, oropharyngeal stimulation of conscious, unrestrained rats with sucrose increases the uptake of radioactive glucose from the small intestine into the hepatic portal blood.

Animals↗

PubMed2000

Oral preanaesthetic medication for children: double-blind randomized study of a combination of midazolam and ketamine vs midazolam or ketamine alone.

Anxiolysis and sedation with oral midazolam are common practice in paediatric anaesthesia. However, good or excellent results are seen in only 50-80% of cases. For this reason, we investigated if addition of a low dose of oral ketamine (MIKE: ketamine 3 mg kg-1, midazolam 0.5 mg kg-1) resulted in better premedication compared with oral midazolam 0.5 mg kg-1 or ketamine 6 mg kg-1 alone, in a prospective, randomized, double-blind study. We studied 120 children (mean age 5.7 (range 2-10) yr) undergoing surgery of more than 30 min duration. After oral premedication in the ward and transfer, the child's condition in the induction room was evaluated by assigning 1-4 points to the quality of anxiolysis, sedation, behaviour at separation from parent and during venepuncture (transfer score). On days 1 and 7 after operation, parents were interviewed for changes in behaviour (eating, sleep, dreams, toilet training), recollection and satisfaction, using a standardized questionnaire. The groups were similar in age, sex, weight, intervention and duration of anaesthesia. The transfer score was significantly better in the MIKE group (12.5 (95% confidence interval (CI) 11.9-13.1)) than in the ketamine or midazolam groups (10.6 (9.8-11.4) and 11.5 (10.7-12.3), respectively). Success rates for anxiolysis and behaviour at separation were greater than 90% with the combination, approximately 70% with midazolam and only 51% with ketamine alone. The incidence of salivation, excitation and psychotic symptoms was low in all groups. Vertigo and emesis before induction were significantly more frequent after ketamine premedication. During recovery, there were no differences in sedation or time of possible discharge. After 1 week, parents reported nightmares (ketamine five, midazolam three, MIKE one), restless sleep (five/four/four) or negative memories (three/four/one). There were no major or continuing disturbances in behaviour or development. In summary, significantly better anxiolysis and separation were observed with a combination of ketamine and midazolam, even in awake children (sedation was not successful according to the preset criteria), than with midazolam or ketamine alone. Duration of action and side effects of the combination were similar to those of midazolam. The combination of both drugs in strawberry flavoured glucose syrup (pH 4.5 approximately) is chemically stable for 8 weeks.

Anesthesia Recovery Period↗

PubMed1999

Dental side effects of an oral device to treat snoring and obstructive sleep apnea.

STUDY OBJECTIVES: Snoring and obstructive sleep apnea (OSA) are common and related conditions--with major social and health implications--which can be treated successfully with dental devices that reposition the mandible. Despite wide use, side effects of these devices have not yet been systematically evaluated. The purpose of the study was to evaluate side effects of a mandibular advancement splint (MAS) previously described by the authors. DESIGN: Questionnaire survey and dental examination of a consecutive case series of patients treated with the MAS SETTING: Dental outpatient clinic PATIENTS: Attempts were made to contact all 191 patients treated over a 5-year period. All had snored loudly and habitually with or without OSA prior to treatment. MEASUREMENTS AND RESULTS: Of 191 patients treated, 132 agreed to complete the questionnaire. All were scheduled to attend for dental examination and 106 underwent examination. Of the 132 interviewed, patient and partner report indicated that the device was well tolerated and controlled snoring satisfactorily in 100 after 31 +/- 18 (mean +/- SD) months of use. Dental side effects were reported in 107 patients, although these were mostly minor, and only 10 patients ceased using the device because of them. Side effects included excess salivation (in 40), xerostomia (in 30), temporomandibular joint pain (in 35), dental discomfort (in 35), myofacial discomfort (in 33) and bite changes (in 16). Of 106 patients examined, 30 had increased maximal opening and 76 had no change compared with pretreatment records. Temporomandibular joint noises were found in 9 patients, and occlusal changes (12 m mylar strip and wax bite, relative to pretreatment) in 15. None of these effects could be related to degree of opening or protrusion produced by the MAS. CONCLUSION: Dental side effects occur in a significant proportion of patients using the MAS. In most cases these are minor and their importance must be balanced against the efficacy of the MAS in treating snoring and OSA.

Adult↗

PubMed2003

Association between nocturnal bruxism and gastroesophageal reflux.

STUDY OBJECTIVE: To examine the relationship between nocturnal bruxism and gastroesophageal reflux. DESIGN: Controlled descriptive study and double-blind, placebo-controlled, clinical study. SETTING: Portable pH monitoring, electromyography, and audio-video recordings were conducted during the night in the subjects' home. PARTICIPANTS: Ten patients with bruxism and 10 normal subjects were matched for height, weight, age, and sex. They did not have symptoms of gastroesophageal reflux disease. INTERVENTION: Medication with a proton pump inhibitor (ie, a gastric-acid-inhibiting drug). MEASUREMENTS AND RESULTS: The bruxism group showed a significantly higher frequency of nocturnal rhythmic masticatory muscle activity (RMMA) episodes (mean +/- SD: 6.7 +/- 2.2 times per hour) and a higher frequency and percentage of time of gastroesophageal reflux episodes with a pH less than 4.0 and 5.0 (0.5 +/- 0.9 and 3.6 +/- 1.6 times per hour and 1.3% +/- 2.5% and 7.4% +/- 12.6%, respectively) than the control group (RMMA episodes: 2.4 +/- 0.9 times per hour; gastroesophageal reflux episodes: 0.0 +/- 0.0 and 0.1 +/- 0.3 times per hour and 0.0% +/- 0.0% and 0.0% +/- 0.0%, respectively). In the bruxism group, 100% of the gastroesophageal reflux episodes with a pH less than 3.0 and 4.0 included both an RMMA episode and an electromyographic burst, the duration of which was approximately 0.5 to 1.0 seconds, probably representing swallowing of saliva. The majority of gastroesophageal reflux episodes with a pH of 4.0 to 5.0 also included both an RMMA episode and an electromyographic burst in the control and bruxism groups (100% +/- 0.0% vs 70.7% +/- 16.5%), again probably due to swallowing of saliva. The remaining minority of gastroesophageal reflux episodes with a pH of 4.0 to 5.0 contained only an electromyographic burst (swallowing of saliva). The frequency of RMMA episodes after the release of the medication from the proton pump inhibitor, which increased the gastric and esophageal pH, was significantly lower than that after administration of the placebo in the control and bruxism groups (1.0 +/- 0.6 vs 1.9 +/- 3.2 times per hour, and 3.7 +/- 1.9 vs. 6.0 +/- 2.2 times per hour, respectively). CONCLUSIONS: Nocturnal bruxism may be secondary to nocturnal gastroesophageal reflux, occurring via sleep arousal and often together with swallowing. The physiologic link between bruxism and the increase in salivation needs to be investigated.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2001

Preclinical safety evaluation of avasimibe in beagle dogs: an ACAT inhibitor with minimal adrenal effects.

Avasimibe, a novel inhibitor of acyl coenzyme A:cholesterol acyltransferase (ACAT), is currently being developed as an antiatherosclerotic agent. The preclinical safety and toxicokinetics of the compound were assessed in beagle dogs in an escalating-dose study and in repeated-dose studies of 2-, 13-, and 52-week duration. Oral (capsule) doses up to 1000 mg/kg b.i.d. were assessed in the escalating dose study and once-a-day doses up to 300 mg/kg, 1000 mg/kg, and 1000 mg/kg were assessed in the 2-, 13-, and 52-week studies, respectively. Avasimibe was found to be a substrate and inducer of hepatic CYP 3A, producing pronounced decreases in plasma drug concentrations subsequent to Day 1. Plasma drug concentrations plateaued markedly at doses above 100 mg/kg. Significant toxicologic findings were restricted to the higher doses (> or =300 mg/kg) and included emesis, fecal consistency changes, salivation, body weight loss, microscopic and clinical pathologic evidence of hepatic toxicity, and red blood cell (RBC) morphology changes. Mortality occurred at 1000 mg/kg due to hepatic toxicity. Toxicity was more closely associated with the exaggerated pharmacodynamic effects of the compound (e.g., marked serum cholesterol decreases) seen at the high doses of avasimibe used in these studies rather than with measures of systemic exposure (Cmax or AUC). Adrenal effects were noted only in the 52-week study and consisted of minimal to mild cortical cytoplasmic vacuolization and fibrosis at doses > or =300 mg/kg, with no change in adrenal weight. In conclusion, avasimibe is an ACAT inhibitor that has minimal adrenal effects in dogs, with dose-limiting toxicity defined by readily monitored and reversible changes in hepatic function.

Acetamides↗

PubMed1988

Comparison of MAC and the rate of rise of alveolar concentration of sevoflurane with halothane and isoflurane in the dog.

The anesthetic requirements for sevoflurane, isoflurane, and halothane were determined in mongrel dogs. The MACs (minimum alveolar concentration) of sevoflurane, isoflurane, and halothane were 2.36 +/- 0.46% (n = 18), 1.39 +/- 0.25% (n = 10), and 0.89 +/- 0.20% (n = 12), respectively (mean +/- SD). In agreement with sevoflurane's low blood/gas partition coefficient (0.6), the rate of rise of alveolar concentration toward that inspired (FA/FI) for sevoflurane was significantly faster than that for either halothane or isoflurane. Thirty seconds after breathing a constant inspired concentration FA/FI was 0.75 for sevoflurane, which was 2.96 times higher than that with halothane (0.25 +/- 0.02) and 1.29 times higher than that with isoflurane (0.6 +/- 0.05). Induction with sevoflurane was smooth, with no struggling nor excessive salivation.

Anesthesia, Inhalation↗

PubMed1990

Dexmedetomidine, an alpha 2-adrenoceptor agonist, reduces anesthetic requirements for patients undergoing minor gynecologic surgery.

The effects of dexmedetomidine, an alpha 2-adrenoceptor agonist, on vigilance, thiopental anesthetic requirements, and the hemodynamic, catecholamine, and hormonal responses to surgery were investigated in healthy (ASA physical status 1) women scheduled for dilatation and curettage (D & C) of the uterus. Fifteen minutes before induction they received single iv doses of either dexmedetomidine (0.5 micrograms/kg; n = 19) or saline (n = 20) in a double-blind fashion. Anesthesia was induced with thiopental and maintained with N2O/O2 (70/30%) and thiopental. Dexmedetomidine was well tolerated and no serious drug-related subjective side-effects or adverse events were observed. The most prominent subjective effects were fatigue and decreased salivation. The total amount of thiopental needed to perform D & C of the uterus was reduced approximately 30% (from 456 +/- 141 mg [mean +/- SD] after saline to 316 +/- 79 mg after dexmedetomidine). This was mostly due to a smaller induction dose in the group receiving dexmedetomidine. Dexmedetomidine appeared to improve the recovery from anesthesia as measured by visual analogue scales (VAS) on fatigue and nausea. The plasma concentration of norepinephrine was decreased by 56% after dexmedetomidine implying decreased sympathetic nervous activity. Systolic and diastolic blood pressure were moderately reduced after dexmedetomidine administration. The authors conclude that dexmedetomidine preanesthetic medication decreases thiopental anesthetic requirements and improves the recuperation from anesthesia with no serious hemodynamic or other adverse effects. Further studies in patients undergoing more stressful surgery are indicated.

Adrenergic alpha-Agonists↗

PubMed1995

Characteristics of the analgesic effects and drug interactions of intrathecal carbachol in rats.

BACKGROUND: Intrathecal carbachol produces consistent analgesia in animals without appreciable adverse effects. Little is known about the ability of this drug to provide analgesia as stimulus intensity is increased. Likewise, there are few data regarding interactions between carbachol and other intrathecal analgesics. METHODS: Using two different noxious radiant heat intensities, one applied to each hind limb, analgesic effects of 1, 3, 10, and 30 micrograms intrathecal carbachol on paw withdrawal latencies were measured. Similar testing was done for intrathecal morphine and clonidine. ED50 fractions (1/2, 1/4, 1/8, 1/16) of drug combinations of carbachol-morphine and carbachol-clonidine were administered, responses to the low intensity stimulus were recorded, and the ED50 of each combination was established and isobolographic analysis of the drug interactions was carried out. RESULTS: The 30-micrograms dose of carbachol was associated with transient agitation, salivation, and hind limb weakness. No other adverse effects were noted. The ED50 (95% confidence interval) of intrathecal carbachol was 2.34 micrograms (1.34-4.04) for low intensity stimulation and 12.64 micrograms (4.18-38.25) for high intensity. There was no significant difference between high- and low-intensity ED50 values for intrathecal morphine and clonidine. The analgesic effect of the carbachol-morphine and carbachol-clonidine combinations were significantly greater than the calculated additive effects. The ED50 for the carbachol-morphine combination was 12% of the expected additive value and the ED50 for the carbachol-clonidine combination was 30% of the expected additive value. CONCLUSIONS: Intrathecal carbachol provides analgesia to noxious thermal stimulation of the hind paw in rats. It is relatively less effective at providing analgesia than intrathecal morphine or clonidine when stimulus intensity is raised. Intrathecal carbachol is synergistic when combined with intrathecal morphine or clonidine.

Analgesics, Non-Narcotic↗

PubMed2000

A dose-ranging study of rapacuronium in pediatric patients.

BACKGROUND: The aim of this study was to determine the dose or doses of the new rapid-onset, short-acting, neuromuscular blocking drug rapacuronium that would provide satisfactory conditions for tracheal intubation at 60 s in infants and children. METHODS: Sixty-five infants (< 1 yr), 51 younger children (1-6 yr), and 49 older children (7-12 yr) were studied. Anesthesia was induced with thiopental-nitrous oxide-oxygen. Tracheal intubation was attempted 60 s after administration of one of five doses of rapacuronium (0.5, 1.0, 1.5, 2.0, or 2.5 mg/kg) and intubating conditions were assessed using a four-point scale. Following tracheal intubation, anesthesia was maintained with nitrous oxide-oxygen and alfentanil (12.5-50 microg/kg) as necessary. Neuromuscular transmission was monitored in an uncalibrated fashion using an acceleromyograph. RESULTS: Intubating conditions were good or excellent at 60 s in all infants after doses of 1.5 mg/kg or more and in all younger and older children after doses of 2.0 mg/kg or more. The duration of action of rapacuronium was dose- and age-dependent. Mean times to reappearance of the third twitch of the train-of-four (TOF; T3) were less than 10 min in infants at doses of 1.5 mg/kg or less and in younger and older children at doses of 2.0 mg/kg or less. Recovery of T3 after 1.0-2.0 mg/kg rapacuronium was significantly slower in infants compared with younger (P = 0.001) and older (P = 0.02) children. Five adverse experiences were related to rapacuronium administration: Bronchospasm (two instances), tachycardia (one instance), and increased salivation (two instances). None were serious. CONCLUSIONS: Doses of 1.5 and 2.0 mg/kg rapacuronium can produce satisfactory intubating conditions at 60 s in anesthetized infants and children, respectively, and are associated with a short duration of action.

Age Factors↗