Cimetidine and neonatal small bowel adaptation: an experimental study

Histamine2-blockers are being used more extensively in the pediatric short gut patient as an agent to accelerate small bowel adaptation. Reversal of lipid malabsorption and a direct trophic effect on the intestinal crypt cells have been postulated as the mechanism for the salutary influence of cimetidine. Weanling Sprague-Dawley rats underwent 85% small bowel resection. Controls had repair of a simple ileal transection. Rats received either a fat-defined rat chow only, or chow with high- or low-dose cimetidine, 2% cholestyramine, or cholestyramine/low-dose cimetidine. All animals were killed 2 weeks postresection, and ileal and jejunal sections were examined for changes in villous and crypt morphology. The animals receiving cimetidine showed earlier and more consistent weight gain than resected animals who received no adjunctive treatment. High- and low-dose regimens were equally efficacious. Cimetidine administered alone decreased fecal fat losses, but not when given with cholestyramine. The cimetidine/cholestyramine group showed increased weight gain when referenced to the resection controls despite continuing lipid malabsorption. Villous and crypt lengthening did not correlate with clinical evidence of adaptation. An augmented lymphocytic activity (plasma cell hyperplasia, enlargement Peyer's patches) was present in the hyperplastic ileal segments of the cimetidine-treated rats. Overall immunoreactivity was similar in all study groups. No significant differences in villous morphology or immunologic activity were seen in jejunal segments. The effects of H2-blockers on lipid absorption and intestinal hyperplasia are inadequate to explain the benefits of cimetidine in the short gut patient. Examination of the immunology of the short bowel complex merits further attention in elucidating cimetidine's action in this setting.     

Developmental sequelae in premature infants undergoing ligation of patent ductus arteriosus

One hundred sixteen infants who underwent on-unit ligation of patent ductus arteriosus (PDA) were examined for developmental sequelae. Mean gestational age of the study group was 29.1 weeks; mean birth weight, 1,232 gm; and mean duration of follow-up, 20.7 months (chronological age). Seven infants died of severe bronchopulmonary dysplasia (4) and severe central nervous system dysfunction (3) before they were 3 years old. Sixty-five percent of the remaining infants exhibited normal motor and mental development, although 58% showed some degree of postnatal growth retardation. There was no evidence of left arm dysfunction caused by the thoracic incision; 3 infants had minor problems with nonabsorbed sutures at 3 to 6 months of age. No infant demonstrated recurrence of ductal patency. Mild sensorineural handicaps not expected to be of long-term importance were noted in 20 infants. Eighteen other infants (15.5%) were classified as having moderate to severe impairments, which may have substantial impact on development and ability to function. Surgical ligation of PDA in premature infants has been shown to be safe and effective in the short run. Long-term follow-up suggests that infants who undergo PDA ligation do not appear to be at increased risk for sensorineural handicaps.     

Gastroschisis in 106 consecutive newborn infants

Primary tissue closure of gastroschisis remains controversial. Some surgeons routinely place a silicone rubber sheet silo over the exposed bowel, planning a staged closure. In the past 14 1/2 years, we have cared for 106 newborns with gastroschisis, closing the defect primarily in 80%. The success of this technique depends on enlarging the abdominal cavity and decreasing the volume of bowel that must be replaced in the peritoneal cavity. Thorough preoperative rectal irrigation should evacuate all meconium. After undermining the skin around the abdominal wall defect for only 1 cm, a midline subcutaneous fasciotomy is created from the xiphoid to the pubis. The abdominal wall is then stretched in all quadrants beginning at the flanks. The eviscerated small bowel can often be returned without enlarging the initial skin defect. The skin is closed with subcuticular absorbable sutures reinforced by long skin tapes. The small ventral hernia that results is closed at about 1 year of age. Fascia could be closed primarily in 28% of these patients, and 17% required a prosthetic pouch. The duration of postoperative ileus and length of hospital stay were statistically significantly shorter in the infants who underwent primary closure. Even though more complicated patients were included in the primary closure group, the incidence of mortality and morbidity was not higher than in patients treated with silicone rubber pouches. Deaths were inevitable in five infants with gangrenous bowel, multiple anomalies, and extreme prematurity. Deaths were related to sepsis in three infants and were the result of operative or anesthetic technique in four. Only two preoperative factors were prognostic of morbidity and mortality: gestational age (but not birth weight) and the presence of intestinal ischemia or atresia.     

Etiology of intestinal damage in gastroschisis, II. Timing and reversibility of histological changes, mucosal function, and contractility

Previous work in the fetal lamb examined the relative effects of amniotic fluid and bowel constriction in the etiology of bowel damage in gastroschisis. The present study used the same model to assess the timing and reversibility of these changes during gestation. Gastroschisis was created at 80 days' gestation, and a tape was placed around the bowel to cause gradual constriction with growth. Lambs were killed at 100 days, 120 days, and term. Bowel damage was assessed using histology, mucosal enzyme activity, and in vitro motility. In an additional "repaired" group, the constrictor was removed at 120 days, a silastic pouch placed over the bowel, and bowel damage assessed at term. Normal fetuses at each gestational age were used as controls. A fibrous peel was observed at all gestational ages. Mucosal villous atrophy and mesenteric venous and lymphatic dilation were mild at 100 and 120 days, but severe at term. These changes were present but mild in repaired animals at term. Mucosal enzyme activity decreased gradually with gestational age; inhibition of maltase activity was maximal at term, and was significantly reversed by repair, whereas inhibition of aminooligopeptidase activity was maximal at 120 days, and was not affected by repair. Protein/DNA, DNA/weight, and protein/weight ratios showed that repaired mucosal cells were significantly more proliferative, smaller, and less mature than control or gastroschisis cells. In vitro motility studies demonstrated a mild decrease in contractility at 100 and 120 days, and a large decrease at term. This deleterious effect at the end of gestation was only partially reversed by repair in utero.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combined topical and systemic antibiotic prophylaxis in experimental wound infection

The effectiveness of a combined topical and systemic antibiotic regimen was studied in an animal model previously shown to simulate clinical surgical wound infection. At a high level of bacterial contamination, the combination regimen produced a lower infection rate than either a placebo (p < 0.01), a topical antibiotic administered alone (p < 0.01), or a systemic antibiotic administered alone. At a lower level of bacterial contamination, no additional reduction in infection rates was produced by the combination regimen when compared with systemic antibiotic administered alone. These experimental results suggest that when wound contamination is great, a combination of topical and systemic antibiotics is the more effective regimen. Where wound contamination is less severe, systemic antibiotic prophylaxis is all that is required; no further benefit is obtained by the additional administration of topical antibiotics. Clinical trials appear justified to confirm or refute this hypothesis.     

Urinary tract stone after small bowel bypass for morbid obesity

There is a marked increase in the incidence of urinary tract stones in patients who have undergone intestinal bypass for obesity. Increased urinary excretion of oxalate is a regular finding in such patients. Taurine and cholestyramine did not influence hyperoxaluria in the two patients tested with each drug. In patients with small bowel bypass, caloric intake is an important factor in determining the magnitude of hyperoxaluria.We do not believe that the resultant susceptibility of these patients to renal calculi is a contraindication to intestinal bypass; however, it is a potential complication that should be considered preoperatively and brought to the attention of the patient.     

Etiology of intestinal damage in gastroschisis. I: Effects of amniotic fluid exposure and bowel constriction in a fetal lamb model

Gastroschisis is often complicated by damage to the herniated small bowel, resulting in motility and absorption disturbances and occasional intestinal necrosis and atresia. To study the pathophysiology of this process, a model of gastroschisis was developed in fetal lambs. At 80 days' gestation, the anterior abdominal wall was partially excised to create a small peritoneal cavity, and the small bowel was extruded through a Silastic ring to create a defect of uniform size. In one experimental group, a tie was placed around the herniated bowel at the level of the abdominal wall to provide gradual constriction as the fetus grew. In a second group, no tie was placed. Control animals had a simple laparotomy and no abdominal wall defect; some also had a constrictor placed around the base of the bowel. The animals were delivered near term, and the bowel was evaluated histologically and by an in-vitro bowel motility assay. Histologic examination showed normal ganglion cells in all groups and no evidence of ischemic injury. A fibrous peel was seen only in bowel exposed to amniotic fluid, with or without a constrictor. Lymphatic and venous dilation, smooth-muscle thickening, and focal mucosal blunting were seen in bowel subjected to chronic obstruction by a constrictor, regardless of whether it was exposed to amniotic fluid. Both constriction of the bowel and amniotic fluid exposure were associated with a decrease in motility; these two effects were independent and additive.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gunshot wounds of the colon: A review of 100 consecutive patients,with emphasis on complications and their causes

The cases of one hundred civilian patients with gunshot wounds of the colon treated at the Louisville General Hospital have been reviewed. Most injuries were in the transverse colon (44 per cent), followed by the ascending colon (27 per cent), rectosigmoid (19 per cent), and descending colon (10 per cent). Associated injuries occurred in 81 per cent of the patients; the small bowel was the most common structure injured.Primary closure was used in 52 per cent of the patients, with a resultant 19 per cent rate of wound infection and 14 per cent rate of serious complication. When the extent of contamination or tissue destruction required resection, an attempted primary anastomosis was followed by a high rate of wound infection (57 per cent) and serious complications (36 per cent) as compared with end-colostomy and mucous fistula, which resulted in a 24 per cent rate of wound infection and 24 per cent rate of serious complication. The rate of wound infection between these groups is significant (p = 0.05). Results with end-colostomy and mucous fistula were better than with attempted primary anastomosis.Primary closure of missile injuries of the colon is feasible but should not be attempted in the presence of gross fecal peritonitis or massive tissue destruction. If resection is undertaken, end-colostomy (or ileostomy) and distal mucous fistula should be performed in the presence of intra-abdominal contamination to reduce the incidence of postoperative wound infection and serious complications. Delayed primary closure should also reduce the rate of wound infection in these patients.     

Prevention and reversal of intestinal failure-associated liver disease in premature infants with short bowel syndrome using intravenous fish oil in combination with omega-6/9 lipid emulsions

Although premature infants with short bowel syndrome are at the highest risk of developing intestinal failure-associated liver disease (IFALD), they have great capacity for intestinal growth and adaptation if IFALD can be prevented. Conventional soybean oil-based intravenous lipid emulsions have been associated with IFALD. This study presents data on 5 premature neonates with short bowel syndrome treated with a combination of parenteral fish oil- and olive/soybean-based lipid emulsion for periods ranging between 7 and 17 months. Despite an enteral tolerance of less than 50% in 4 of these patients during their first year of life, direct bilirubin levels normalized while on this combination of ClinOleic (Baxter, Maurepas, France)/Omegaven (Fresenius Kabi, Bad Homburg, Germany) at a 1:1 ratio. None of our patients developed irreversible IFALD even though all of them were premature, had undergone multiple major surgical procedures, and had experienced several episodes of sepsis. Thus far, we have not seen any adverse effects of this mixed lipid emulsion in these preterm infants. All 5 patients are growing and developing well and have normal liver function.     

Erythrocyte sodium-potassium-stimulated adenosine triphosphatase activity is not related to obesity

Altered erythrocyte sodium potassium (Na,K)-stimulated adenosine triphosphatase (ATPase) activity has been cited as having pathophysiologic significance in morbidly obese man. Previous studies have failed to consider obese patients after weight loss and, therefore, did not clarify the role of ATPase deficiency as a cause or effect of the obese state. To define more completely the possible alteration of cellular thermogenesis in obesity, a study was made of three groups of people: (1) normal weight controls; (2) morbidly obese; and (3) formerly morbidly obese patients who had lost over 100 pounds after gastric bypass surgery. Erythrocyte ATPase activity was determined by use of an assay that coupled ATPase activity with NADH oxidation in the presence of excess pyruvate kinase, lactic dehydrogenase, and phosphoenolpyruvate. This coupled assay produced a continuous slope so that activity could be calculated from the initial, maximal, linear portion of the decay trace. Results did not demonstrate any statistically significant differences in Na,K-ATPase activity between groups by analysis of variance. A nonsignificant correlation of 0.086 was seen between obesity index and Na,K-ATPase activity. It is concluded that (1) erythrocyte Na,K-ATPase activity is similar in both normal and obese individuals, (2) erythrocyte Na,K-ATPase does not change with weight loss, and (3) therefore, disordered erythrocyte thermogenesis does not have a role in the development or maintenance of obesity.     

Factors associated with the resolution of postoperative ileus in newborn infants

Reliable indicators of ileus resolution following laparotomy have not been identified in newborn infants. The purpose of this study was to correlate commonly available clinical parameters with the resolution of postoperative ileus in newborn infants after abdominal procedures. The presentation, treatment, and postoperative abdominal examination of 60 consecutive newborn infants who underwent a heterogeneous group of primary abdominal operations were evaluated. No significant association was observed between the time to first bowel movement (resolution of ileus) and age, postconceptual age, weight, degree of intraabdominal contamination, duration of surgery, type of operative procedure, presence or absence of abdominal distension, and time to first bowel sounds. Opioid use was associated with a delay in the time to first bowel movement that was not accounted for by the effects of any other variable. Easily obtainable clinical parameters are not universally useful for predicting the duration of ileus in newborn infants after abdominal surgery. The use of opioids is associated with delayed resolution of ileus. Measures to limit the use of opioids may be effective in shortening the duration of postoperative ileus in newborn infants.     

Elevated plasma levels of vasoactive intestinal polypeptide in short bowel syndrome

Short bowel syndrome is a complex disease that is almost always seen with diarrhea. VIP is known to act powerfully on gut motility, and elevated VIP plasma levels have been reported in several diarrheal conditions. In this study VIP plasma levels were measured by radioimmunoassay in 8 patients with short bowel syndrome versus 30 healthy control subjects under basal conditions. VIP plasma levels were significantly higher in the short bowel syndrome group (p less than 0.05). The explanations that could account for these elevated levels are (1) an increased gastric acid load in the residual bowel, (2) a compensatory increase in blood supply to the gut, (3) removal of an inhibitory factor arising from the small intestine, or (4) mucosal stress due to unadsorbed food. An etiologic role of VIP in the occurrence of diarrhea in patients with short bowel syndrome seems to be an unproved hypothesis.     

Inefficient substrate utilization: A mechanism of cachexia in cancer

Definition of mechanisms of cachexia and inanition in cancer should improve treatment. To determine the interrelationships between tumor substrate metabolism, caloric intake, and body weight, 24 Buffalo rats were studied. Twelve rats had Morris 7777 tumors implanted and twelve were controls. Animals had daily weights and rat chow intake measured. When tumor-bearing animals lost significant weight (P < 0.05, t test), they were sacrificed with a control animal. The liver from experimental and control animals and the hepatoma from the thigh were excised, homogenized, and mitochondria were isolated. The adenosine diphosphate (ADP)-stimulated respiratory activity (state 3) and ADP-independent respiratory activity (state 4) of mitochondria were determined. The Respiratory Control Index (RCI) was calculated as the most sensitive indicator of mitochondrial oxygen-substrate metabolism. Tumor-burdened rats and controls had statistically equivalent chow consumption (P > 0.05). Tumor mitochondria demonstrated reduced rates of state 3 and state 4 oxygen consumption and RCIs were statistically less than control liver tissue (P < 0.05). From these data we conclude: (1) weight loss in this tumor model is not due to inadequate intake; (2) hepatoma mitochondria are inefficient in use of substrates; and (3) exhaustion of substrates in an inefficient manner may contribute to the catabolism of cancer.     

Low molecular weight dextran in the treatment of necrotizing enterocolitis and midgut volvulus in infants

Because of its abilities to reduce thrombus formation, low molecular-weight dextran was administered to eight newborns with necrotizing enterocolitis and two infants with midgut volvulus. The enterocolitis group which received dextran when compared with an otherwise similarly treated group which did not receive dextran, revealed the following differences: half of the dextran-treated group did not require operation while all of the patients not receiving dextran did. Although repeated perforation and late intestinal strictures occurred commonly in the group which did not receive dextran, no dextran-treated infant demonstrated either of these complications. The patients with midgut volvulus receiving dextran demonstrated remarkable recovery of bowel at reexploration, despite the widespread ischemic appearance of bowel at initial operation. No complications from the use of dextran were encountered.     

The significance of the ileocecal valve in massive resection of the gut in puppies.

Clinical observations suggest that retention of the ileocecal valve is vital for survival in neonates who undergo resection of small bowel to the extent that less than 40 cm remain. Twenty-four puppies underwent 90% resection of small bowel and 12 of these also had a destructive procedure performed on the ileocecal valve. Survival and weight patterns were used to assess results when it was found both parameters supported the clinical observations. The practical application is that all attempts should be made to retain the ileocecal valve in situations in which only short lengths of small bowel remain.     

Lethal short-bowel syndrome

Infants with short-bowel syndrome are difficult to manage. Despite supportive measures with parenteral nutrition and surgery to lengthen remaining bowel or increase functional absorptive surface area, the outcome for many of these infants is poor. We have reviewed a series of seven infants diagnosed with severe short bowel. Causes included volvulus (3), multiple atresias (2), and total intestinal aganglionosis (2). Survival time ranged from 15 days to 8 months. During the hospital course, each infant underwent one to three operative procedures to diagnose and manage the short bowel and all received total parenteral nutrition (TPN) ranging from 10 days to 6 months. One infant died of liver failure and two others developed significant liver dysfunction secondary to TPN. Most infants remained hospitalized until their death. Death occurred at an average of 9 weeks following the diagnosis of short-bowel syndrome. This review suggests that infants with less than 6 cm of small bowel beyond the Ligament of Treitz will inevitably die of their disease or treatment complications. Until bowel transplant becomes a viable alternative, operative intervention and nutritional support may prolong survival but will not change the outcome of these infants and will only contribute to additional morbidity. A decision to withhold further therapy would be reasonable at the time the diagnosis is established.     

Isoperistaltic bowel lengthening for short bowel syndrome in children

BACKGROUND: Short bowel syndrome, secondary to a variety of causes, can be lethal in infancy and childhood. Isoperistaltic bowel lengthening, performed by longitudinal division of dilated small bowel with end-to-end anastomosis, has shown early promise but long-term outcome is unknown. METHODS: Sixteen infants and children (aged 3 months to 14 years) had short bowel syndrome from necrotizing enterocolitis (8), gastroschisis (4), atresia (2), and volvulus (2). All of these patients were partially or totally dependent on parenteral nutrition and have undergone isoperistaltic bowel lengthening for short bowel syndrome (length <100 cm). Bowel length was increased by 22% to 85% (mean 42%) with the procedure. Studies of intestinal function were performed preoperatively and postoperatively. RESULTS: Isoperistaltic bowel lengthening resulted in significant improvement in stool counts, intestinal transmit time, intestinal clearance of barium, D-xylose absorption, and fat absorption at 6 months and 12 months postoperatively. Fourteen of 16 patients (88%) have been weaned from parenteral nutrition. CONCLUSIONS: These data show that isoperistaltic bowel lengthening can be an effective operation for short bowel syndrome in children, improving absorption and motility, and allowing weaning from parenteral nutrition.     

Assessment of gastric motility using meal labeled with technetium-99m sulfur colloid

During a 2 year period, 83 patients with gastric motility problems were evaluated using radionuclide imaging. The patients presented with epigastric distress, postprandial fullness, pain, nausea, vomiting, and diarrhea; signs and symptoms suggestive of either gastroparesis or gastric outlet obstruction. Upper gastrointestinal series or endoscopy, or both, demonstrated no mechanical obstruction. After oral administration of a 300 g meal labeled with 600 muCi of technetium-99m sulfur colloid, a gastric emptying study consisting of serial images and data acquisition was performed. Of the patients studied, 52 had had peptic ulcer surgery, 17 were suspected of having gastroesophageal reflux, 8 were diabetic and suspected of having visceral enteropathy, and 6 had a history of irritable bowel syndrome. The normal mean gastric half emptying time was 77 +/- 16 minutes. Of the patients who had had gastric surgery, 90.4 percent had abnormal emptying: 69.2 percent had delayed gastric emptying and 21.2 percent had rapid gastric emptying time; 9.6 percent had normal emptying time. Of the gastroesophageal reflux group, all but two had normal gastric emptying time; 65 percent demonstrated gastroesophageal reflux within 15 minutes. Two of the patients with irritable bowel syndrome had prolonged emptying; the rest had normal emptying. All diabetic patients with gastroparesis had prolonged gastric emptying time, and all responded favorably to metoclopramide. Of the patients who previously had peptic ulcer surgery and had prolonged emptying time, 72 percent also responded favorably to metoclopramide. We conclude that radionuclide gastric imaging is a useful diagnostic test for the measurement of gastric emptying in patients with a variety of gastrointestinal motility disorders and may be helpful in assessing medical therapy and selecting those who may be candidates for surgery.     

Notice from the Southern Thoracic Surgical Association

Fifty infants ranging in age from 13 days to 18 months (mean age 6 months) and weighing from 1.7 to 8.2 kg (mean weight 4.5 kg) underwent patch closure of a ventricular septal defect (VSD) with use of deep hypothermic circulatory arrest. Seventeen infants were under 3 months of age. The principal indication for operation was intractable chronic congestive heart failure. All infants were below the third percentile for weight preoperatively. Three patients (6%) died postoperatively within the second month of life. There was no late mortality. Seven infants (14%) had seizures; these were associated with a low output state in 2 infants, with hypoxic episodes in 4 infants, and occurred postoperatively in 1 infant. Postoperatively, 8 (17%) of the surviving infants developed right bundle-branch block and left anterior hemiblock, and 16 (32%) developed right bundle-branch block alone. One year postoperatively, catheterization studies in 24 children revealed normal pulmonary artery pressure and pulmonary vascular resistance in all; there were no significant residual ventricular septal defects. Because of these results we continue to be enthusiastic about primary closure of VSD irrespective of age or weight.