Ontogeny of insulin-like growth factor 1 in a rabbit model of growth retardation.

Many cases of intrauterine growth retardation (IUGR) result from placental insufficiency, but the molecular signals accompanying this event are unknown. Insulin-like growth factor 1 (IGF-1) is a potent mitogen for fetal tissues and is lowered in the serum of human infants with IUGR. The rabbit provides an optimal model for the study of IUGR based on fetal position. To determine if IGF-1 expression is altered in the growth-retarded fetus, this naturally occurring rabbit model of IUGR was used. Four fetal rabbit pairs were harvested on Days 21, 23, 25, 27, 29, and 31 of their normal 31-day gestation; they were identified based on uterine position as normal or growth retarded. Fetal weight was recorded and the serum, amniotic fluid, liver, kidney, and small intestine (SI) were collected. The SI was divided into three equal segments: proximal, middle, and distal. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure IGF-1/beta-actin mRNA densitometric band ratios in all tissues. Radioimmunoassay (RIA) was used to measure IGF-1 protein levels in the serum and amniotic fluid. Statistical analysis was performed using ANOVA and the paired Student's t test. Weights were decreased in fetuses with IUGR at all time points (P < 0.05), further validating this rabbit model in the study of IUGR. Liver, proximal, and distal SI IGF-1 mRNA decreased during late gestation (P < 0.01). Kidney IGF-1 mRNA increased throughout late gestation (P < 0.01). Compared with their normal counterparts, fetuses with IUGR had a trend toward decreased IGF-1 mRNA in the kidney, liver, and SI at all time points, reaching significance in the liver on Day 27 (P = 0.002). Serum IGF-1 decreased throughout gestation in all fetuses (P < 0.05). Compared with normal fetuses, fetuses with IUGR had lower serum IGF-1 at all time points, reaching significance at Day 27 (P = 0.02). Amniotic fluid IGF-1 was lower in fetuses with IUGR than in normal fetuses, though not quite reaching significance. Compared with normal fetuses, growth-retarded fetal rabbits trend toward depressed liver, kidney, and intestinal expression of IGF-1 mRNA and lower serum and amniotic fluid IGF-1 protein. Serum IGF-1 levels correlate with fetal weight change. Further studies and potential manipulation of fetal IGF-1 are warranted to investigate potential prenatal intervention in the treatment of IUGR.

Effect of dexamethasone on insulin-like growth factor-1 expression in a rabbit model of growth retardation.

BACKGROUND/PURPOSE: The maternal administration of steroids promotes fetal maturative effects in the gastrointestinal tract. To determine if fetal insulin-like growth factor-1 (IGF-1) expression is altered in response to maternal dexamethasone administration, this rabbit model of intrauterine growth retardation (IUGR) was utilized. METHODS: Eight pregnant rabbits received either dexamethasone (Dex 0.1 mg/kg/d intramuscular), or normal saline (Cont) on gestational days 26 and 27. Fetuses were harvested on gestational day 28 or 29 and were identified as favored (Fav) or runt (Runt): DexFav, DexRunt, ContFav, and ContRunt. Fetal weight was recorded and the serum, amniotic fluid, liver, kidney, and small intestine (SI) were collected. Reverse transcription polymerase chain reaction (RT-PCR) was used to measure IGF-1/beta-actin mRNA densitometric band ratios in all tissues. Radioimmunoassay (RIA) was used to measure IGF-1 protein levels in the serum and amniotic fluid. RESULTS: Weight was decreased in the Runt fetuses at all time-points (P < .08). The percent weight accretion from day 28 to 29, was greatest in the DexRunt fetus (P < .001), suggesting "catch-up" growth. All Dex fetuses (Fav and Runt) had increased liver and proximal, middle and distal SI IGF-1 mRNA at day 28 and elevated levels in the liver, proximal and distal SI at day 29 compared with control fetuses. The DexRunt fetuses had serum IGF-1 protein surpassing that of the DexFav fetus at day 28. CONCLUSIONS: This report provides the first description of maternal steroid administration effecting a marked increase in fetal IGF-1 mRNA expression and IGF-1 protein levels in an in vivo rabbit model of IUGR. The growth-retarded fetus appears to be particularly responsive.

The outcome of research training during surgical residency.

BACKGROUND/PURPOSE: Graduates of a university surgical residency program were surveyed to identify the timing of specialty selection and the impact that studying in a research laboratory had on subsequent acceptance into a fellowship program. METHODS: Between 1975 and 1990, 86 residents completed general surgery training at UCLA Medical Center. A survey was sent to all graduates to determine the focus of their previous laboratory research and when they selected their eventual surgical specialty. Responses were received from 67 of the 86 graduates (78%). RESULTS: Forty-eight of the sixty-seven respondents (72%) took one or more years of surgical research during residency. Postresidency fellowship training was selected by 55 of 67 (82%); 50 applied to fewer than five programs; 49 of 55 (89%) received one of their top three choices. Twenty-seven of the sixty-seven residents pursued an academic career (40%). Residents who performed at least 2 years of research were more likely to become academicians (53%) than residents who did 1 year or less of research (22%). Only 39 of 67 residents (58%) had selected a specialty after 2 years of clinical training; 28 more made the selection after the third clinical year. All residents interested in cardiac surgery (n = 18) or plastic surgery (n = 4) prior to research were accepted into fellowships in those specialities, whereas only 37% of those who had an interest in other fields pursued the same specialty (P < 0.0001). Residents performing research in general surgery (n = 9), surgical oncology (n = 18), cardiac surgery (n = 14), and plastic surgery (n = 3) were more likely to practice in that specialty than those doing research in other specialty laboratories. CONCLUSIONS: General surgery residents performing research in a specialty laboratory are likely to pursue fellowship training relating to that field. Those who select a career in cardiac or plastic surgery prior to research are most likely to enter into these fields as their eventual specialty. Residents who perform 2 or more years of laboratory research publish more papers and often pursue an academic career.

Congenital gastrointestinal pacemaker cell tumor.

The interstitial cells of Cajal complex within the gut wall function as a pacemaker to direct peristalsis. Their neoplastic counterpart is the gastrointestinal pacemaker cell tumor, a spindle and/or epithelioid cell mesenchymal tumor previously known as gastrointestinal stromal tumor or incorrectly called leiomyosarcoma in some cases of older reports. Although numerous cases of gastrointestinal leiomyosarcomas have been documented in the English-language literature, no pediatric case of gastrointestinal stromal tumor or gastrointestinal pacemaker cell tumor has, to our knowledge, been recorded. Herein, we report a case of congenital gastrointestinal pacemaker cell tumor confirmed by immunohistochemistry and electron microscopy in a full-term male newborn.

Pulmonary arteriovenous malformation complicating coccidioidal pneumonia.

A patient was treated for lobar pneumonia due to coccidioidomycosis. When the pneumonia recurred, the patient was found to have an arteriovenous malformation, which had become infected. Complete resolution was achieved with resection and postoperative amphotericin B therapy.

Effect of prenatal dexamethasone administration: fetal rabbit intestinal nutrient uptake and disaccharidase development.

To examine the effect of prenatal steroids on fetal intestinal maturation, eight pregnant rabbits received either dexamethasone (Dex) or saline (Cont) on Days 25-27 of a 31-day gestation. As the rabbit provides a model of growth retardation based on uterine position, fetuses were identified as favored (Fav) or runt (Runt), generating four study groups: ContFav, ContRunt, DexFav, and DexRunt. On Day 31 the small intestinal uptake of glucose and proline was measured by an everted sleeve technique. Additionally, lactase and maltase activity was determined. Small intestinal length and nutrient uptake was significantly increased in the Dex fetuses. Control runts had a trend to decreased levels of nutrient uptake when compared to their favored counterparts. This trend reversed in the Dex fetuses with runt nutrient uptake surpassing that of the favored fetus. A trend to increased enzyme activity of both lactase and maltase was demonstrated. This report provides the first description of maternal steroid administration causing a marked increase in fetal small intestinal length and glucose and proline absorption in an in vivo model of intrauterine growth retardation.

Transamniotic fetal feeding: enhancement of growth in a rabbit model of intrauterine growth retardation.

BACKGROUND: Transamniotic fetal feeding has been proposed as prenatal treatment for intrauterine growth retardation as substrates infused into the amniotic cavity are swallowed and absorbed. The rabbit provides an optimal model of intrauterine growth retardation in that a consistent weight ratio of the runt to the favored fetus is found at term. METHODS: Thirty growth-retarded rabbit fetuses underwent transamniotic catheterization in the third trimester with incremental infusion of either dextrose, dextrose plus amino acids, or bovine amniotic fluid. One week later fetal weights were determined. The ipsilateral favored fetus served as an operated, noninfused control. RESULTS: Fetuses receiving amniotic fluid showed significantly increased somatic growth when analyzed by absolute body weight and by weight ratio versus control. Increases in the liver, lung, and small intestinal weights of the fetuses receiving amniotic fluid paralleled the overall increase in somatic weight. No differences were found in the dextrose or dextrose plus amino acid-infused groups. CONCLUSIONS: The increased amount of ingested amniotic fluid, or fetal "force feeding," appears responsible for enhanced growth because bovine and native rabbit amniotic fluid have only negligible differences. This study provides the first report of successful growth augmentation of a fetal rabbit runt with prenatal transamniotic fetal feeding.

Impairment of nutrient uptake in a rabbit model of gastroschisis.

Infants with gastroschisis (GS) commonly require total parenteral nutrition and prolonged hospitalization because of intestinal dysfunction resulting from dysmotility and/or malabsorption. To investigate prepartum small intestinal (SI) nutrient absorption in GS, a fetal rabbit model was surgically created on gestational day 24 (term, 31 to 33 days) in 11 time-mated New Zealand White does in each left ovarian-end fetus. Each right ovarian-end fetus served as a control (C) and was manipulated only. All does, 10 of 11 GS fetuses (91%), and 8 of 11 C fetuses (73%) survived to gestational day 30. GS fetuses had significantly reduced total body weights, SI weights, and SI lengths compared with C fetuses. Using the everted mucosal sleeve technique, the uptakes of an amino acid (proline) and a sugar (glucose) were determined. The uptakes of proline per milligram SI, proline per centimeter SI, and glucose per milligram SI were significantly impaired in GS fetuses compared with C fetuses (P < .04 by Student's paired t test). The uptake of glucose per centimeter SI was also reduced in GS fetuses, but not significantly. Uptake capacities (a measure of the entire SI's ability to absorb a given nutrient) were significantly reduced in GS fetuses compared with C fetuses (proline, 2,670 +/- 612 nmol/min/entire SI v 6,842 +/- 399 nmol/min/entire SI, P < .008 by Student's paired t test; glucose, 402 +/- 69 nmol/min/entire SI v 950 +/- 103, P < .008 by Student's paired t test).

Assessment of alkaline reflux in children after Nissen fundoplication and pyloroplasty.

During an eight month period, 22 children less than 15 years of age (mean age of three years and seven months) who underwent operative treatment of gastroesophageal reflux (GER) were selected for study. All were symptomatic and unresponsive to medical therapy. Preoperative evaluation included esophageal pH probe monitoring in 18 patients, gastric isotope emptying study in 18 patients and contrast studies of the upper part of the gastrointestinal tract in ten patients. Four children with severe neurologic disorders who required placement of a feeding gastrostomy tube underwent fundoplication without preoperative evaluation. All 22 patients had GER and 14 had documented delayed gastric emptying (greater than 60 percent residual at 90 minutes) on radionuclide scan with appropriate meal for age. Each child underwent Nissen fundoplication and tube gastrostomy. Sixteen patients also had a modified pyloroplasty with a 2.5 to 4.0 centimeter vertical seromuscular incision on the antrum. When the patients achieved a full feeding schedule (postoperative day range three to 21 days, mean of 6.2 days), they were put on a fast for six hours and an aspirate was obtained from the gastrostomy tube. Analysis of pH and bile acid content served as indicators of alkaline reflux. The six children without pyloroplasty served as the control group. Intragastric pH ranged from 1.91 to 7.00 (mean of 3.71) and bile acid content ranged from 4 to 150 micrometers per liter (mean of 62 micrometers per liter). No significant differences were seen between patients with fundoplication alone and those with fundoplication and pyloroplasty (p = 0.97 for pH; p = 0.66 for bile acid content). Two patients with pyloroplasty showed slight elevation of intragastric bile acid content at the upper limits of normal. At follow-up evaluation from nine to 23 months (mean of 18 months), all patients were asymptomatic, with only two showing rare gagging. Additionally, nine patients have had complete resolution of their pulmonary symptoms. No patients demonstrated diarrhea, gas bloat or dumping. Nissen fundoplication combined with a modified pyloroplasty or "antroplasty" for delayed gastric emptying provides excellent clinical results with minimal demonstrable bile acid reflux and no change in intragastric pH at the one and one-half year follow-up evaluation.

Reduction of wound infection in high-risk surgical patients.

During a 9-year period, 183 consecutive patients underwent total colectomy and the endorectal ileal pull-through procedure (ERIPT) for ulcerative colitis (UC) (n = 156), familial polyposis (n = 25), or Hirschsprung's disease (n = 2). The average age was 29.4 years (range 7.1-59.1 years). All patients with UC were steroid-dependent at the time of operation. Two groups were retrospectively reviewed based on the management of their midline abdominal wounds. Ninety consecutive patients underwent the ERIPT procedure between 1983 and 1987 with stapled skin closure and perioperative intravenous antibiotics (group 1A). Between 1988 and 1992, 93 patients had abdominal wall closure in the same manner, however, the wounds were probed daily in four to six sites for the first five postoperative days with a Q-tip moistened with 2 per cent aqueous mercurachrome solution (group 2A). Approximately four months after ERIPT, ileostomy closure was performed on 176 of the patients, of whom 89 had no wound probing (group 1B), and 87 had probing (group 2B). Following colectomy and the ERIPT procedure, 22/90 group 1A patients (24.4%) and 4/93 group 2A patients (4.3%) developed wound infections. Following ileostomy closure only 3/89 (3.4%) group 1B patients and 1/87 (1.2%) group 2B patients developed wound infections. No group 2A or B patients required wound packing, and none had prolonged hospitalization. In contrast, 17 group 1A patients spent more than 1 extra day of hospitalization (mean 2.8 days) and required wound packing a mean of 22.6 days after hospital discharge. This wound infection rate is significantly lower for group 2A versus 1A patients (P < 0.0001, ANOVA).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of esophageal ligation on the development of fetal rabbit intestinal lactase.

To investigate the effect of normal fetal swallowing and amniotic fluid ingestion on small intestinal disaccharidase development, 13 pregnant New Zealand White rabbits underwent operation on day 24 of a normal 31-day gestation. The right ovarian fetus in the bicornuate uterus underwent esophageal ligation (EL), while the contralateral left fetus underwent cervical exploration only, and served as the control (C). Rabbits were sacrificed on gestational day 31, fetal somatic measurements obtained, and the midjejunum removed for determination of disaccharidase activity and protein content. There was one maternal death, and 9 of 12 fetal pairs survived the entire study period (75%). Results are reported as mean +/- SEM, analyzed by two-tailed Student's t testing with P < .05 being considered significant. Fetal weight was decreased in EL (48.6 +/- 2.7 g) versus C (51.4 +/- 3.2 g) (P = .06). Small intestinal length decreased in EL (49.2 +/- 2.0 cm) versus C (54.9 +/- 1.1 cm) (P = .01). Midjejunal protein content (mg/mL homogenate) was also significantly decreased in EL (38.4 +/- 3.4) versus C (46.2 +/- 3.7) (P = .05). Sucrase activity was not detectable in either group. Lactase activity in jejunal mucosa was not effected when expressed as units of enzyme per milliliter of homogenate (EL = 0.357 +/- 0.03 v C = 0.373 +/- 0.04; P = .70) and units enzyme per gram of protein (EL = 38.8 +/- 4.2 v C = 34.2 +/- 4.6; P = .44). We have confirmed previous studies demonstrating decreases in somatic growth, small intestinal length, and mucosal nutrient transport in rabbit fetuses following esophageal ligation.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of transamniotic administration of epidermal growth factor on fetal rabbit small intestinal nutrient transport and disaccharidase development.

As fetal swallowing is documented in utero, supplementation of the ingested amniotic fluid with nutrients or hormones has been postulated as a potential prenatal treatment for intrauterine growth retardation (IUGR). To study the effect of epidermal growth factor (EGF) on the developing fetal small intestine, 12 pregnant rabbits underwent operation on day 24 of a normal 31-day gestation. Bilateral ovarian end fetuses underwent catheterization of their respective amniotic cavities with attachment to a miniosmotic pump. Study fetuses received recombinant human EGF at approximately 300 micrograms/kg/d for 1 week; controls received carrier solution only at an equivalent rate. On gestational day 31, fetuses were delivered by cesarean section and somatic measurements were recorded. The small intestine was harvested and proximal, middle, and distal regions were analyzed for lactase and maltase enzyme activity. Additionally, the uptake of radiolabeled glucose and proline was measured by a standard everted mucosal sleeve technique for each segment. Results were analyzed by Student's paired t test and reported as mean +/- SEM. Nine fetal pairs survived (75%). Small intestinal (SI) length was increased in EGF fetuses (54.8 +/- 1.9 cm) versus control (50.4 +/- 2.7 cm) (P = .02). Lactase activity, reported as UE/g protein, was significantly increased in the proximal segments in the EGF-infused fetuses; maltase was significantly increased in both the proximal and middle segments (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of anabolic steroids on ameliorating the adverse effects of chronic corticosteroids on intestinal anastomotic healing in rabbits.

The ability of anabolic steroids to reverse the deleterious effects of chronic corticosteroids on intestinal anastomotic healing was studied in 32 rabbits. Rabbits received once daily intramuscular injections of saline solution (controls), 0.1 milligram per kilogram of dexamethasone, dexamethasone plus low-dose anabolic steroids (2 milligrams per kilogram of nandrolone decanoate) or dexamethasone plus high-dose anabolic steroid (10 milligrams per kilogram of nandrolone decanoate). Two weeks later, the rabbits underwent small intestinal (SI) or large intestinal (LI) anastomoses. Postoperatively, injections were continued as before with the addition of high-dose anabolic steroids (20 milligrams per kilogram of nandrolone decanoate) to one-half of the dexamethasone only group. Seven days postoperatively, the rabbits had in situ assessment of anastomotic bursting pressure (ABP) and histologic examination using a modified Ehrlich/Hunt scale. Results demonstrated that dexamethasone severely impaired the healing of SI and LI anastomoses, with decreases in ABP to almost 50 percent of normal values and with similar reduction in histologic parameters. High-dose anabolic steroids reversed this inhibitory effect when initiated preoperatively or post-operatively, with increase in ABP to 72 percent of normal for SI anastomoses and 83 percent of normal for LI. No adverse effect of anabolic steroid administration was evident.

Upregulation of nutrient transport in fetal rabbit intestine by transamniotic substrate administration.

Delivery of nutrients to the developing fetal gastrointestinal tract has been advocated as a potential prenatal treatment for intrauterine growth retardation. To examine the effect of intrauterine nutrient administration on the uptake capacity of the intestine, 16 maternal rabbits underwent bilateral ovarian-end transamniotic catheter placement on gestational Day 24. Study fetuses received a galactose solution; the contralateral controls received mannitol, a physiologically inert carbohydrate. Infusions were continued until Day 30 when an everted sleeve technique was used to measure radiolabeled uptake of both galactose and glucose in the proximal, middle, and distal small intestine. Mucosal scrapes were obtained, weighed, and the percentage of weight was calculated. Results were analyzed by ANOVA and Student's t test with P less than 0.05 being considered significant. There were 2 maternal deaths with 11 fetal pairs surviving (79%). There was increased uptake of galactose in the study fetuses compared to controls reaching significance in the middle and distal segments. Similarly, glucose uptake was significantly increased in the proximal and distal segments. Mucosal weight was increased in all regions, reaching significance in the proximal segment. Total intestinal uptake of galactose and glucose was significantly increased in the study fetuses compared to controls. Intraamniotic galactose infusion caused not only upregulation of its own mucosal transport but also that of glucose, along the entire fetal small intestine, achieving statistical significance particularly in distal segments. Fetal implications for transamniotic feeding are under investigation.