Pseudoathetosis: report of three patients.

We report on 3 patients with pseudoathetosis, which are involuntary, slow, writhing movements due to loss of proprioception.     

Serotonin-induced increase in cAMP in ganglia isolated from the myenteric plexus of the guinea pig small intestine: Mediation by a novel 5-HT receptor

Serotonin (5-HT) is a mediator (through 5-HT_1P receptors) of slow EPSPs in myenteric ganglia of the small intestine. The effect of 5-HT can be mimicked by elevating cAMP; therefore, we tested the hypothesis that the slow EPSP-like response to 5-HT is cAMP-mediated. Guinea pig gut was enzymatically dissociated; myenteric ganglia remained intact and were collected by filtration. Neurons in the isolated ganglia retained their ability to manifest the slow EPSP-like response to 5-HT. Exposure to 5-HT raised the ganglionic level of cAMP (ED₅₀ 0.3 μM). This effect was not antagonized by the 5-HT_1P antagonist, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (100.0 μM), or mimicked by the 5-HT_1P agonist, 5-hydroxyindalpine (10.0 μM). Increases in cAMP were also evoked by the 5-HT₁ agonist, 5-carboxyamidotryptamine (10.0 μM), the 5-HT₂ agonist, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 1.0–10.0 μM), and by the 5-HT₄ agonists, renzapride (1.0–10.0 μM) and 5-methoxytryptamine (1.0–10.0 μM); however, neither the 5-HT₁/5-HT₂ antagonists, spiperone, methysergide, and methiothepin, nor the 5-HT₄ antagonist, tropisetron (ICS 205–930; 10.0 μM), were able to inhibit the rise in cAMP evoked by these compounds or by 5-HT (0.1–10.0 μM). The 5-HT-evoked elevation of cAMP was antagonized by ketanserin (10.0 μM), which also blocked the effects of 5-methoxytryptamine and DOI, but not those of renzapride. The effective concentration of DOI, however, was higher than that needed for activation of 5-HT₂ receptors, and Northern analysis using a cDNA probe encoding the rat 5-HT₂ receptor failed to reveal the presence of 5-HT₂ mRNA in myenteric ganglia, although it hybridizes with mRNA of the right size in the guinea pig brain. Compounds that failed to change levels of cAMP or to antagonize the action of 5-HT included 8-hydroxy-di-n-propylamino tetralin, R58639, R88226, and sumatriptan. It is concluded that the receptor responsible for the 5-HT-induced rise in cAMP in ganglia isolated from the guinea pig myenteric plexus is not a known subtype of 5-HT receptor. Since the pharmacology of this novel receptor is different from that of the slow EPSP-like response to 5-HT, the receptor probably does not mediate the slow EPSP. © 1993 Wiley-Liss, Inc.     

Congenital diaphragmatic defects that present late.

Twenty two patients (age range: 1 month to 11 years) were treated for congenital diaphragmatic defects (excluding hiatus hernia) in the six year period 1983-8. Presenting features were failure to thrive (n = 7), abdominal pain and vomiting (n = 4), chronic respiratory symptoms (n = 3), and inability to wean from ventilatory support (n = 3). The defect was an incidental finding in five patients. Operative repair was performed with no mortality or serious postoperative morbidity. Dramatic improvement occurred in 15 of the 17 symptomatic patients. Awareness of the differential diagnosis should avoid delay in diagnosis or inappropriate treatment. Surgical correction is strongly recommended in all cases.     

The development of a comprehensive, institution-based patient risk evaluation program: II. Validity and reliability of questionnaire data

The accuracy of historical information derived from self-administered questionnaires must be confirmed. We report the results of studies conducted to assess the reliability and validity of data collected from a comprehensive cancer risk factor questionnaire developed at The University of Texas M.D. Anderson Cancer Center. A comparison of the basic demographic data of a randomly selected sample of 80 respondents and 70 nonrespondents revealed no fundamental ethnic or socioeconomic differences. We verified self-reported past illnesses, surgical procedures, and cancers by reviewing 72 patient charts, using stringent diagnostic criteria for verification. We noted substantial agreement between self-reported and documented illnesses and operations. With the exception of nine patients who misclassified metastatic disease, the verification of primary cancers was excellent. We determined reliability by interviewing 50 of these patients by telephone. Questions with a dichotomous outcome (e.g., smoking status) were reliably answered; however, those requiring quantification (e.g., amount of alcohol consumed) were less accurately reported on interview. While we recognize the limitations of self-administered questionnaires, we believe this program will develop into a comprehensive, standardized, easily accessible patient risk factor data base.     

Psychiatric disorders in the first-degree relatives of probands with bulimia nervosa

Data from a family study of psychiatric disorders showed higher rates of major affective disorders, eating disorders, and alcoholism in first-degree relatives of 40 bulimic probands than in first-degree relatives of 24 control subjects. More importantly, the data showed higher rates of major affective disorders in relatives of bulimic probands who themselves had no history of major affective disorders than in relatives of control subjects. This significant finding indicates a familial relationship between bulimia nervosa and major affective disorders, which suggests the possibility of a common diathesis.     

Study of the drug release mechanism from tyrphostin AG-1295-loaded nanospheres by in situ and external sink methods.

The present study focused on in vitro release of polylactide-nanoencapsulated tyrphostin AG-1295, a potential agent for local therapy of restenosis. The drug was formulated in matrix-type nanoparticles, termed nanospheres (NS) using the nanoprecipitation method. AG-1295 is a model for low-molecular weight lipophilic compounds, the release behavior of which cannot be adequately characterized by existing methods. An in vitro release technique suitable for optimizing the nanoparticulate formulation release behavior was developed through a novel external sink method and an in situ release method utilizing the environmental sensitivity of the AG-1295 fluorescence spectrum. Similar tendencies were demonstrated by both methods in drug release studied as a function of selected NS preparation variables. The release properties of the drug fractions varying in their binding mode to the carrier particles were studied by the external sink method. The NS surface-adsorbed drug exhibited a significantly higher release rate compared to the drug entrapped in the polymeric matrix. The in situ release of the encapsulated drug was analyzed using the diffusion models of release from a matrix-type sphere. The release was shown to be a composite process, with a burst phase attributed largely to the rapid dissociation of the surface-bound AG-1295. The diffusion-controlled phase exhibited an alteration in kinetic pattern obviously due to the drug distribution between polymeric matrix compartments differing in their permeability. Drug in vitro release investigation may be effectively used to characterize the drug-carrier interaction and internal carrier structure in nanoparticulate formulations, as well as optimize the release behavior in respect to their therapeutic application.     

Gastric transposition for esophageal substitution in children.

Fifty-four gastric transposition procedures have been carried out for esophageal substitution in the 10-year period 1981 through 1990. The indication for esophageal replacement was esophageal atresia in 36 (19 long-gap atresia with distal fistula and 17 isolated atresia), caustic stricture in 9, intractable peptic reflux stricture in 3, 2 achalasia and 1 each of prolonged foreign body impaction, diffuse leiomyoma, congenital esophageal stenosis, and congenital short esophagus. Eight patients had previously undergone an unsuccessful colonic replacement procedure. The age at gastric transposition ranged from 4 months to 16 years. The procedure of choice was posterior mediastinal transposition without thoracotomy in 37 cases. The esophagogastric anastomosis leaked in 7 patients (12.9%), all of which closed spontaneously, whereas 5 patients developed an anastomotic stricture that responded to bouginage. There were 5 deaths (9.2%). Major complications developed postoperatively in 12 patients: 4 required additional gastric drainage procedures, 2 required temporary tracheostomy, 2 developed adhesion obstruction, and 1 each developed paraesophageal hernia, leakage of the jejunal feeding tube, tracheomalacia, and major hemorrhage following resection of a colonic graft. Major but temporary feeding problems were encountered in 12 children. Medium-term results were assessed as excellent in 67%, good in 20%, fair in 6%, and poor in 6% of the 34 patients surviving longer than 1 year postoperatively (ie, excluding 7 patients lost to follow-up).     

Gastro-oesophageal reflux and intestinal malrotation in children

In a series of 74 children undergoing Nissen fundoplication for persistent gastro-oesophageal reflux unresponsive to intensive medical treatment, there was an unexpectedly high incidence (54 per cent, n = 40) of intestinal malrotation. The series was not homogeneous, 25 of the children having reflux as a complication of a serious congenital abnormality (48 per cent incidence of intestinal malrotation), and 49 presenting with 'idiopathic' reflux (57 per cent incidence of intestinal malrotation). Intestinal malrotation is best detected pre-operatively by careful barium radiology, requiring clinicians to be aware of the association. In our experience, in children over the age of 3 months, both an antireflux operation and Ladd's procedure are often necessary to stop gastro-oesophageal reflux when an intestinal malrotation is present.