Effects of domperidone therapy on symptoms and upper gastrointestinal motility in infants with gastroesophageal reflux

We evaluated the effect of domperidone, a novel prokinetic agent, on symptoms and esophageal and gastric motility in 15 infants (six boys), mean age 7.9 months, with moderate to severe gastroesophageal reflux (GER) and upper gastrointestinal motility disturbances. Patients received domperidone orally for 6 weeks and underwent weekly assessment of five GER-associated symptoms, weight change, and side effects. Mean total symptom scores significantly improved after treatment (P less than 0.01). Vomiting, "spitting," and coughing each improved significantly. Postprandial reflux time (defined as esophageal pH less than 4.0) and percent peristaltic esophageal contractions improved significantly (p less than 0.05). Gastric fundic contractions, present in only four infants before treatment, occurred in nine after domperidone administration. Although mean gastric emptying of isotope-labeled formula was not improved, it improved greater than or equal to 10% over baseline in nine patients. Peristaltic amplitude, lower esophageal sphincter pressure, and esophageal acid clearance time were unchanged. Side effects were minimal. We conclude that domperidone is a useful and safe agent for treatment of gastroesophageal reflex in infants because it addresses the motility abnormalities inherent in the pathophysiology of the disorder.     

Effect of cisapride on nocturnal transient lower oesophageal sphincter relaxations and nocturnal gastro-oesophageal reflux in patients with oesophagitis: a double-blind, placebo-controlled study

AIM: To investigate the effect of cisapride, a selective 5-hydroxytryptamine-4 receptor agonist, on the frequency of nocturnal transient lower oesophageal sphincter relaxations and oesophageal acid exposure in patients with gastro-oesophageal reflux disease. METHODS: In a double-blind, placebo-controlled study, 10 patients with gastro-oesophageal reflux disease (six male and four female; mean age, 54 +/- 10.4 years) were randomly assigned to 5-day treatments with cisapride, 10 mg q.d.s., or placebo, separated by a 2-day washout period before the treatment crossover. Sleep stages, lower oesophageal sphincter tone and oesophageal pH were monitored overnight at the end of each treatment regimen. Gastric emptying was assessed before treatment. RESULTS: Cisapride decreased the frequency of transient lower oesophageal sphincter relaxations during sleep (1.2 +/- 0.2/h vs. 2.7 +/- 0.5/h with placebo; P=0.004) and oesophageal acid exposure (17.2 +/- 9.9% with placebo vs. 7.2 +/- 4.2% with cisapride; P=0.4). Cisapride increased lower oesophageal sphincter tone from 12.7 +/- 2.8 mmHg with placebo to 16.9 +/- 3.9 mmHg (P=0.03), and decreased heartburn episodes and antacid consumption. All patients had normal gastric retention data over 4 h. CONCLUSIONS: In patients with gastro-oesophageal reflux disease, cisapride significantly decreased the frequency of transient lower oesophageal sphincter relaxations during sleep and increased lower oesophageal sphincter pressure without changing gastric emptying. We hypothesize, therefore, that 5-hydroxytryptamine-4 mechanisms are important in the control of transient lower oesophageal sphincter relaxations in humans.     

Vascular risk to late-life depression: evidence from a longitudinal community study

OBJECTIVE: To determine prospectively relationships between minor cerebrovascular episodes and depressive symptoms in a community cohort of older persons. METHOD: In 1988-1989, baseline measurements of vascular risk factors and depressive symptoms were obtained in older community residents (mean age = 67). At 10-year follow-up, three subgroups of subjects still residing in the community were re-assessed: those who had suffered a transient ischaemic attack (TIA) (n = 16) in the intervening period; those with hypertension but no TIAs (n = 38); and, those with neither TIAs nor hypertension (n = 40). RESULTS: Of the 16 persons with depressive symptoms at 10-year follow-up, only three had reported depressive symptoms initially. Subjects who had experienced TIAs during the longitudinal phase had higher rates of depressive symptoms than the subjects from the other two groups (38%vs 13%, p < 0.05). CONCLUSIONS: This study supports the notion that cerebrovascular incidents predispose to late-onset depression in older persons residing in the community. Intrinsically, this provides epidemiological support for the validity of the concept of 'vascular depression'.     

Men with nonobstructive azoospermia have Leydig cell hypertrophy but not hyperplasia

PURPOSE: We determined whether testicular histology in men with spermatogenic failure due to nonobstructive azoospermia shows true Leydig cell hyperplasia. MATERIALS AND METHODS: Testicular biopsy specimens from 17 patients evaluated for infertility were retrospectively analyzed. Interstitial, tubular and Leydig cell volume were quantitatively evaluated. The total volume and number of Leydig cells per testicle were then calculated. RESULTS: In 10 patients with obstructive azoospermia testicular histology showed normal spermatogenic function, while 7 had nonobstructive azoospermia. Average testicular volume plus or minus standard deviation was significantly larger in those with obstructive versus nonobstructive azoospermia (18.0 +/- 7.0 versus 9.3 +/- 8.7 cc, p = 0.025). Interstitial versus tubular volume was 32% of the total testis in the obstructive and 63% in the nonobstructive groups (p = 0.003). Although Leydig cell volume was proportionally greater in men with nonobstructive versus obstructive azoospermia (13.3% versus 0.05%, p = 0.045), there was no significant difference in the average number of Leydig cells per testicle (3.96 x 10 and 6.17 x 10, respectively, p = 0.16). The average volume of individual Leydig cells was significantly greater in men with the nonobstructive condition (253.0 +/- 98.7 versus 174.0 +/- 57.7 microm., p = 0.045). CONCLUSIONS: These results suggest that men with nonobstructive azoospermia and those with normal spermatogenesis have an equivalent number of Leydig cells. However, the Leydig cells are hypertrophic and occupy a larger proportion of total testis volume in men with nonobstructive azoospermia. Therefore, patients with spermatogenic failure show Leydig cell hypertrophy but not hyperplasia.     

Comparison of intussusception pull-through end-to-side and conventional end-to-side microsurgical vasoepididymostomy: prospective randomized controlled study in male wistar rats

PURPOSE: Vasoepididymostomy is a technically challenging and complex microsurgical procedure. Recently a new triangulation end-to-side microsurgical technique was reported that allows intussusception of the epididymal tubule into the vasal lumen, resulting in a higher clinical patency rate of 92% with shorter operative time in preliminary clinical studies. We performed a prospective controlled randomized study comparing the patency rate, postoperative sperm granuloma rate and operating time of conventional and intussusception end-to-side vasoepididymostomy in previously vasectomized rats. MATERIALS AND METHODS: We randomized 42, 6-week-old male Wistar rats into 4 groups, including 6 into the sham operation, and 12 each into the control, conventional end-to-side and intussusception end-to-side vasoepididymostomy groups. Bilateral 2-clip vasectomy was performed in all animals except those in the sham operation group. Bilateral intussusception or conventional end-to-side vasoepididymostomy was performed in the assigned animals 2 weeks after vasectomy. Animals in the control group underwent vasectomy only. In the sham operation group the testes were mobilized out of the scrotum and then returned. Rats were sacrificed at 8, 12, 16 and 24 weeks, respectively. The anastomosis and vasectomy sites were inspected for sperm granuloma. To assess patency the abdominal end of the vas was transected and intraluminal fluid was examined microscopically at 400x magnification for the presence of motile sperm. Patency was further confirmed by performing retrograde indigo carmine vasography through the anastomoses. RESULTS: In the intussusception and conventional groups the patency rate was 91.7% and 54.2% (p = 0.004), the sperm granuloma rate was 20.8% and 58.4% (p = 0.035), and average operative time was 65.8 and 67.7 minutes (p = 0.197), respectively. CONCLUSIONS: Intussusception end-to-side vasoepididymostomy is superior to conventional end-to-side vasoepididymostomy with respect to the patency and postoperative sperm granuloma rates. Further investigations are required to confirm such findings clinically in humans.     

Practice MRI: Reducing the need for sedation and general anaesthesia in children undergoing MRI

The aim of this study was to evaluate the effectiveness of a practice magnetic resonance unit, in preparing children to undergo magnetic resonance procedures without general anaesthesia (GA) or sedation. The records of children who attended the practice MRI between February 2002 and April 2004 were retrospectively reviewed. Each record was assessed as to whether the child had passed or failed the practice MRI intervention. Those children who were considered to have passed and were proceeded to a clinical non‐GA MRI had the report of the clinical scan reviewed. If the scan had been reported as non‐diagnostic because of movement artefact it was classified as a failed scan, otherwise it was considered a pass. One hundred and thirty‐four children undertook a practice MRI (age range 4.1–16.1 years, median age 7.7 years, 47% boys) and 120/134 (90%) passed the practice session. In all, 117/120 (98%) subsequently had a clinical non‐GA MRI and 110/117 (94%) passed (median age 7.8 years, 47% boys). Preparation is a safe and effective method to reduce the need for sedation and GA in children undergoing a clinical MRI scan. It provides a positive medical experience for children, parents and staff, and results in cost savings for the hospital.     

Exposure to alcohol in utero: Influence on cognitive function and learning in a northern elementary school population

OBJECTIVES:

To establish the prevalence of fetal alcohol exposure; to compare physical, behavioural and learning patterns of children with significant alcohol exposure in utero with those of a group of children exposed to minimal alcohol; to assess the usefulness of a fetal alcohol syndrome (FAS)/fetal alcohol effect (FAE) score; and to provide feedback to parents, schools and communities.

DESIGN:

Parent questionnaire, complete physical examinations of children, psychometric tests of the children using elements of the Pediatric Early Elementary Examination (PEEX) and the Pediatric Examination of Educational Readiness (PEER), ADD-H comprehensive teachers rating scale (ACTeRS) score, the newly developed FAS/FAE Score, and the Brigance Comprehensive Inventory of Basic Skills to assess language and mathematical achievement. Testers were blinded to the results of the assessments and questionnaires.

SETTING:

Grades 1 to 3 at Sir Alexander MacKenzie School in Inuvik, Northwest Territories.

RESULTS:

Twenty-four per cent of mothers reported frequent or binge drinking, and 76% of mothers reported abstinence or moderate alcohol intake. There were significant ethnic differences; none of the Caucasian mothers reported frequent or binge drinking during pregnancy compared with 40% of Inuvialuit and 33% of Indian mothers. Children with exposure to frequent or binge drinking in utero had smaller palpebral fissures (2.3±0.1 cm versus 2.5±0.3 cm, P<0.01), smaller palpebral fissure to intercanthal distance ratios (0.77±0.05 versus 0.86±0.10, P<0.01) and smaller head circumferences (52.1±1.6 cm versus 53.6±1.6 cm, P<0.01) than those exposed to moderate drinking or abstinence. Children exposed to frequent or binge drinking in utero also demonstrated poorer coordination (P<0.005) and cortical function (P<0.01), attention problems, hyperactivity (ACTeRS), and poorer scholastic achievement in language (P<0.001) and mathematics (P<0.01) than their minimally exposed counterparts. In children in grades 2 and 3, a significant negative correlation was found between FAS/FAE scores and language (r=–0.55, P<0.001) and mathematical achievement (r=–0.28, P=0.20).

CONCLUSIONS:

The prevalence of drinking during pregnancy in the northern population studied was high, and exposure in utero was associated with physical abnormalities, difficulties with coordination and cortical function, and significant delays in language and mathematical achievement. The FAS/FAE score may be useful in predicting success or failure in language development.     

Whole body protein metabolism in children with cancer

Whole body protein synthesis and catabolism were measured using the [ring-2H5]phenylalanine and [1-13C]leucine primed constant infusion technique in 32 paediatric patients with cancer at different stages of treatment. Rates of synthesis (S) and catabolism (C) derived from the [ring-2H5]phenylalanine and [1-13C]leucine models were 4.7 (SD 1.3) (S) and 6.0 (1.5) (C) g/d/kg, and 5.5 (0.8) (S) and 6.8 (1.2) (C) g/d/kg, respectively. These results show that these two tracer techniques give similar results in this study population. Comparison of these values with results previously reported for groups of control children using the [ring-2H5]phenylalanine model (S = 3.69 and 3.93; C = 4.09 and 4.28 g/d/kg) and the [1-13C]leucine model (S = 4.32; C = 4.85 g/d/kg) show that rates of synthesis and catabolism were higher in cancer patients than in controls. Thus whole body protein turnover is increased in children under treatment for cancer. Other indices of metabolism such as plasma amino acids and intermediary metabolites were also measured and showed that, although subjects were in isotopic steady state, there were significant metabolic changes during the course of the primed constant infusions used to measure protein turnover.