Flaxedil (gallamine triethiodide): evidence for a central action.

A central action of gallamine triethiodide has been demonstrated in cats with permanently implanted electrodes that permit direct repetitive stimulation and recording of afterdischarges from cerebral cortex. Systemically administered gallamine produced a consistent and reproducible augmentation of duration of afterdischarge at doses just sufficient to produce skeletal muscle paralysis. Simultaneous examination of expiratory carbon dioxide, blood pressure, body temperature, blood glucose, and direct cortical response to brief single stimuli failed to reveal any consistent peripheral change to which the centrally observed effecte Could be attributed.

Carbamazepine (Tegretol) as an anticonvulsant. A controlled double-blind comparison with diphenylhydantoin (Dilantin).

A large double blind crossover study of carbamazepine (CBZ) in comparison to diphenylhydantoin (DPH) is underway, and the results are presented for the first 20 patients to complete the protocol. The importance of preparatory steps is outlined-beginning with the gathering of preliminary kinetic data about half-life and peak-time in epileptic patients. A detailed pilot study was performed with open administration of the agents and hospitalization during the crossover. Detailed blood level monitoring and dose-equivalence calculations lead to the design of blind crossover protocol from the pilot study. Of the 20 patients reported on at this point, 12 had fewer seizures on CBZ, but 4 of these preferred DPH because of the CBZ side effects. Of the 8 having fewer seizures on DPH, 3 preferred CBZ - leading to a final disposition of 11 on CBZ and 9 on DPH. Mean serum levels were 34.1 mug/ml for DPH and 10.6 mug/ml for CBZ. The patients having fewer seizures on DPH had higher serum DPH levels than those doing better on CBZ, but the opposite was found for the CBZ levels. The implications of this difference are discussed. Over all, DPH and CBZ are effective anticonvulsants of the same general magnitude, but individual patient responses to effects and side-effects will influence their usefulness in any given case.

The effects of SCH 23390 and raclopride on cocaine-induced analepsis and EEG arousal in rabbits.

The effects of the dopamine D1 and D2 receptor antagonists on cocaine-induced, cholinergically-mediated analeptic and hippocampal theta activity in anesthetized rabbits were investigated. Cocaine (2 mg/kg, i.v.) reduced by 35% the duration of loss of righting reflex produced by a 25 mg/kg dose of pentobarbital. This shortening of narcosis time was blocked by pretreating the animals with the D1 antagonist, SCH 23390 (0.1 mg/kg) but not with the D2 antagonist raclopride (1-2 mg/kg). Cocaine (5 mg/kg, i.v.) also produced a short burst of increased hippocampal theta activity in urethane-anesthetized rabbits, which was also blocked by SCH 23390 but not by raclopride. An unexpected finding was that raclopride itself, at 2 mg/kg (i.v.), produced a marked activation of theta activity that lasted for 15-20 min. When cocaine was administered after this time it produced a potentiated theta response, both in duration and in magnitude. These results suggest that in the rabbit, cocaine exerts a cholinergically-mediated behavioral and EEG arousal through a D1 dopamine mechanism. The role of the D2 system is less clear but appears to be antagonistic to the D1-mediated response.

Analgesic drugs in the management of pain.

The use of potent narcotics to control severe pain should be of short duration and limited to patients with acute diseases or inoperable or metastatic cancer who require long-term relief. Continued and prolonged use of narcotics in patients with chronic benign pain is not recommended because of serious behavioral consequences, the development of tolerance, and addiction liability. Long-term use of analgesic drugs in chronic pain usually produces negative behavioral complications that are more difficult to manage than the pain it was desired to eliminate. The use of antidepressant drugs in the pain regimen has been found to provide increased relief of pain and often allows the dose of narcotic analgesic to be reduced or totally eliminated.

Perioperative complications of superior pharyngeal flap surgery in children.

A 7-year retrospective review of perioperative complications associated with surgical correction of velopharyngeal insufficiency was carried out. A total of 219 children who underwent surgery for velopharyngeal insufficiency between the years 1985 and 1992 were reviewed. Gender distribution was 58 percent male and 42 percent female. The mean age was 9.6 years, with a range of 4 to 22 years, at the time of surgery. Fourteen cases (6.4 percent) were considered a difficult intubation. There were 36 patients with early complications (16.4 percent incidence). Of these, 18 had postoperative bleeding and 20 developed airway obstruction. Most of these episodes occurred in the first 24 hours. Three patients required reintubation. Nine children developed sleep apnea after discharge. Four patients required take-down of the pharyngoplasty, while 7 others had revision of the flap. There was 1 death in the 219 patients. In summary, most complications following surgical correction of velopharyngeal insufficiency in our institution occur in the early postoperative period and are the result of bleeding and/or airway obstruction.

Gastroesophageal reflux: a significant association with central nervous system disease in children.

An association between gastroesophageal reflux (GER) and central nervous system (CNS) disease has been suggested, but not defined clearly in children. We report on 613 children (ages 1 week to 16 years; mean, 16 months) studied at three institutions who were referred to the pediatric surgical service for documentation of GER by an abnormal pH score derived from 18- to 24-hour esophageal pH monitoring. Follow-up (range, 1 to 115 months; mean, 25 months) was obtained in 368 patients. One hundred thirty-two children had CNS disease documented prior to the evaluation for GER. In children older than 1 year, there was an increased incidence of GER (31/45, 69%) in those children with CNS disease compared with those without CNS disease (38/81, 47%; P = .014). On follow-up, only 4.6% (14/282) of children who were not diagnosed initially with CNS disease were found later to have overt CNS disease. There was no significant difference in the prevalence of newly diagnosed CNS disease in children with and without GER in long-term follow-up. In conclusion, in the population of children referred to the pediatric surgeon for evaluation of GER, children older than 1 year with CNS disease are at high risk to have associated GER documented by extended esophageal pH monitoring. Despite this association, those children with GER and no obvious CNS disease do not appear to be at increased risk to develop CNS disease.

The mean duration of gastroesophageal reflux during sleep as an indicator of respiratory symptoms from gastroesophageal reflux in children.

The coexistence of gastroesophageal reflux (GER) and respiratory symptoms has been reported in children, but identifying a reliable indicator of reflux-induced respiratory symptoms has been difficult. The mean duration of reflux episodes during sleep (ZMD), extracted from a 18- to 24-hour esophageal pH recording, has been presented previously as a reliable correlate of respiratory symptoms caused by GER in infants. To reexamine the accuracy of the ZMD we report 519 consecutive children with respiratory symptoms (aged 1 week to 15 years) who were referred for documentation of GER by 18- to 24-hour esophageal pH monitoring. Follow-up information was obtained on 388 patients 1 to 115 months later (mean, 23 months). From the follow-up information, 259 children could be reliably classified; 128 as having reflux-related and 131 as having reflux-unrelated respiratory symptoms. None of the 131 children with reflux-unrelated respiratory symptoms had a prolonged ZMD (greater than 3.8 minutes). In comparison, 119 of the 128 children (93%) with reflux-related respiratory symptoms had a prolonged ZMD (P less than .001). The nine children who had a normal ZMD and improvement in their respiratory symptoms with the successful control of GER had advanced esophagitis (n = 4), central apnea (n = 3), or associated disorders in which respiratory symptoms improved with the avoidance of oral feedings (n = 2). In conclusion, the ZMD was confirmed to correlate directly with both the presence and absence of respiratory symptoms caused by GER in children.

The risk of sudden infant death from gastroesophageal reflux.

Gastroesophageal reflux (GER) has been a suspected cause of infant deaths and sudden infant death syndrome (SIDS). We examined our 10-year experience with 499 consecutive infants 6 months of age or less who had extended (18 to 24 hours) esophageal pH monitoring performed to evaluate for GER. The data extracted from the esophageal pH records included the pH score, the pattern of GER (type I, II, or III), and the mean duration of reflux during sleep (ZMD). All infants were followed to determine the occurrence and cause of death during the first year of life. Of the 19 deaths found in the series, three were classified as SIDS and two were in-hospital deaths caused by reflux-induced aspiration. All five of these infants who died had a prolonged ZMD (greater than 3.8 minutes) and received either basic medical (n = 4) or no (n = 1) antireflux therapy. Four infants also had the type I pattern of GER. There was a 9.1% (4/44; 95% confidence limits, 2.5% to 21.7%) incidence of reflux-related or SIDS deaths in infants with type I GER and a prolonged ZMD who were treated nonoperatively, compared with none (0/83, P = .03) in the same group of infants treated with antireflux surgery. The incidence of SIDS was higher in infants with type I GER and a prolonged ZMD who were treated nonoperatively (3/44, 6.8%) compared with all other infants treated nonoperatively (0/265, 0%; P = .003).(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous gastric pH monitoring in children: the effect of gastric emptying on the measurement of gastric acid secretion.

Continuous gastric pH monitoring offers the opportunity to evaluate gastric acid secretion in humans without the need for collection of gastric aspirates. However, gastric emptying may be an important variable for the accurate measurement of gastric acid secretion using continuous gastric pH monitoring. We conducted an in vitro study (phase I) to evaluate the effect of gastric emptying on gastric pH. The in vitro study used a laboratory model in which continuous pH monitoring of a standard formula (Nutramigen, 100 mL) in a reservoir was performed while varying both the reservoir emptying rate (10% to 80%) over 1 hour and the amount of added acid (2 to 15 mEq/h: in vivo equivalent of 6 to 45 mEq/m2 BSA/h). An in vivo study (phase II) was then performed in 28 infants less than 6 months of age who had gastroesophageal reflux (GER) documented by 18- to 24-hour esophageal pH monitoring. At the end of esophageal pH monitoring, the pH electrode was advanced into the stomach for measurement of gastric pH continuously for 2 hours after a feeding of Nutramigen formula (300 mL/m2 BSA). Each patient also had a radionuclide gastric emptying study performed with the same volume of Nutramigen formula. In the in vitro model, the reservoir pH (% time pH less than 4) was proportional to the reservoir emptying rate only when acid was added at less than 15 mEq/h (less than 45 mEq/m2 BSA/h). Reservoir pH was independent of reservoir emptying rate when acid was added at 15 mEq/h (45 mEq/m2 BSA/h).(ABSTRACT TRUNCATED AT 250 WORDS)

Prescribing practices for pain in drug dependence: a lesson in ignorance.

Chronic pain syndromes arise when usual strategies to treat pain and its underlying pathology fail, excessive reliance on medication is related to increased dysfunction and, there is suspicion of psychiatric component to the pain behaviors exhibited. Opiate and sedative medications are generally cited as a contributing factor in the development of chronic non-malignant pain. The recent proliferation of clinics specializing in treatment of chronic pain and related disorders is a new and interesting development. These units consider detoxification from sedatives and opiates mandatory if chronic pain is to be treated and function restored. A literature review shows an amazing paucity of rigorous research in chronic pain patients which supports the widely held belief that medications contribute to dysfunction in chronic pain thus patients require detoxification. The following discussion explores the data upon which are based current strategies for the use of narcotics in chronic pain.