Rigid bronchoscopy in the pediatric age group: diagnostic effectiveness. Over a 15-year period, 277 diagnostic bronchoscopic procedures were carried out at the Winnipeg Children's Hospital using rigid bronchoscopic instrumentation. The objective of the review is to examine contribution to final diagnosis made by the procedure. The patient population included 60% male and 40% female patients ranging from the first day of life to 18 years (mean age, 6 years). Indications for bronchoscopy fell into two large groups, including 60% of patients with evidence of lower airway disease and 30% of patients with evidence of upper airway obstruction. In patients with upper airway obstruction, half were found to have a congenital underlying cause and half were due to an acquired lesion. In 85% of patients, a specific diagnosis was reached and this proved to correlate positively with the preoperative diagnosis in 80% of patients and negatively in 20%. Definitive treatment in patients with upper airway obstruction included surgical intervention in one third of patients. Patients with lower airway disease were diagnosed as having consolidation in 43%, atelectasis in 39%, and bronchiectasis in 18%. Disease localized most frequently to the left lower and right upper lobes and in only 10 of 168 patients was a congenital cause determined. Among 168 patients, 30 had surgical treatment as the definitive management with the majority of patients treated medically. Bronchoscopy was shown to contribute to diagnosis in 88% of patients examined. Bronchoscopy was carried out with a complication rate of 3% and no mortality.


The use of indium 111 leukocyte scans in children with inflammatory bowel disease. Indium 111 leukocyte (WBC) scans have been used in the investigation of inflammatory bowel disease in recent years, but their use in children is not well described. We reviewed our experience with 281 indium 111 scans over an 8-year period in a total of 109 children with inflammatory bowel disease (Crohn's disease 70, ulcerative colitis 39). One hundred twenty-eight indium 111 scans done within 2 weeks of a radiographic contrast study, endoscopic examination, or surgical procedure were evaluated for diagnostic accuracy. Analysis showed that indium 111 scans were accurate when compared with conventional diagnostic tests and operative findings. This noninvasive imaging technique can play a useful role in the management of children with inflammatory bowel disease.


Diaphragm of the gallbladder: a case report. Gallbladder anomalies are rare and normally affect its shape, size, and position. We report on a 3-year-old boy with a gallbladder divided transversally by a windsock-type diaphragm, isolating the fundus from the rest of the biliary tree. Bilobed and multiseptated gallbladder have been described before, but this is the first isolated case of a congenital hourglass gallbladder.


Agenesis of the gallbladder in duodenal atresia: two case reports. Agenesis of the gallbladder not associated with biliary atresia is quite rare. We wish to report two patients with gallbladder agenesis in association with duodenal atresia without biliary atresia. Liver biopsy in one patient was notable for an absence of both inflammation and ductal pathology. The unremarkable postoperative course included normal direct bilirubins and a HIDA scan that demonstrated very good bile excretion into the duodenum. Both children are doing quite well in follow-up.


Cholelithiasis in newborns and infants.

Cholelithiasis in newborns and infants. Cholelithiasis in infants is rare, and has usually been associated with hemolysis, ileal disease, congenital anomalies of the biliary tree, hyperalimentation, and prolonged fasting. With the increased use of abdominal ultrasonography (US), more cases of cholelithiasis are being discovered. We report our experience with 13 infants diagnosed on abdominal US to have gallstones. There were 9 boys and 4 girls with an average age at diagnosis of 2.6 months (range, 0 to 9 months). Predisposing factors could be identified in only 6 of the 13 patients. Two patients with obstructive jaundice underwent cholecystectomy and common bile duct exploration. One patient with choledocolithiasis and common bile duct dilatation was observed. His stone passed spontaneously, with resolution of symptoms. Ten patients without cholestasis remained asymptomatic, with disappearance of lithiasis in five of them. Neonatal cholelithiasis is more common than previously suspected; it seems to affect males more often than females and is usually not associated with known predisposing factors. It appears to be a temporary, self-limiting phenomenon, and an aggressive approach is not warranted in the asymptomatic infant. Surgical or radiological intervention should be reserved for the symptomatic patients or those with underlying lithogenic disorders.


Coagulopathy associated with large sacrococcygeal teratomas. Twelve neonates with sacrococcygeal teratoma (SCT) have been treated at British Columbia Children's Hospital over the past 5 years. Clinically significant coagulopathy developed in four of these neonates and two died, one before surgical intervention could be undertaken. Disseminated intravascular coagulation (DIC) was found in one patient and thrombocytopenia in another on preoperative laboratory studies. Etiology of the coagulopathy is unclear, but appears to be multifactorial. Although several clinical reviews have noted mortalities due to exsanguinating hemorrhage, no study has focused solely on this issue. The diagnosis of SCT in the neonate at high risk for development of coagulopathy is usually made prenatally. Premature labor is often precipitated by associated polyhydramnios and large tumor size. Fetal distress, prematurity, and low birth weight are common. Presence of placentamegaly, hydrops fetalis, and congestive heart failure are ominous prognostic signs. Early identification of patients at increased risk for development of hemorrhagic complications may allow optimization of their management. Cesarean section should minimize trauma to the SCT during delivery. Expeditious resection of the lesion may improve survival.


Cystic neuroblastoma.

Cystic neuroblastoma. In the newborn, cystic masses of the adrenal gland are unusual findings and most are secondary to hemorrhage. We present a patient with a clinical history typical for adrenal hemorrhage who was found to have a thick walled cystic adrenal mass on both physical and ultrasound examination. During evaluation the mass decreased in size, but vanillylmandelic acid (VMA) and homovanillic acid (HVA) levels were elevated. Laparotomy and left adrenalectomy confirmed the diagnosis of a cystic neuroblastoma. Adrenal cyst, adrenal abscess, and cystic neuroblastoma are all rare entities in the newborn. We recommend that all cystic masses of the adrenal be evaluated by urinary VMA and HVA and that the possibility of cystic neuroblastoma be kept in mind when an adrenal cystic mass is followed nonoperatively.


Inguinal hernias in very low birth weight infants: incidence and timing of repair. Although the increased occurrence of inguinal hernias (IH) in premature children is well known, its incidence in the very low birth weight (VLBW, < 1,500 g) subpopulation has not been previously established. Additionally, because of associated problems, these children present the surgeon with a dilemma in regards to the most appropriate time for repair. We sought to determine the incidence of IH, rate of incarceration, perioperative problems, and to possibly define the ideal time for correction. Between 1977 and 1987, 1,933 children under 1,500 g birth weight were admitted to our neonatal intensive care unit. Of these, 1,391 lived for at least 28 days and were followed until 20 months corrected age. IH was diagnosed in 222 of 1,391 (16%) of those who survived 28 days or more. IH occurred in 174 of 670 (26%) of the boys and 48 of 721 (7%) of the girls. The incidence by side was right 19.8%, left 14.9%, bilateral 61.7%, and was unclear 3.6%. Of the 222 infants with IH, 192 were operated at our institution at a mean postnatal age of 28 weeks (range, 5 to 110 weeks). Of these, 35 were operated prior to neonatal discharge. One or more incarcerations occurred in 35 VLBW operated at this hospital. In only one infant, an emergency operation was needed because of irreducibility. There was no operative mortality and minimal morbidity. Five recurrences occurred during the 20 months' follow-up. This series establishes the incidence of IH in VLBW (during the first 20 months). The wide range in age at operation suggests that no single criterion can be established for ideal timing of repair.(ABSTRACT TRUNCATED AT 250 WORDS)


The nutrition of the fetus with intestinal atresia: studies in the chick embryo model. This article examines the effects of experimental prenatal intestinal obstruction on the growth and blood composition of chick embryos. Intestinal atresia (IA) was produced by bipolar bowel electrocoagulation in fertile eggs on the 14th day of incubation. The chicks killed on the 19th day were measured, weighed, and blood-sampled. Twenty-three control, 10 sham-operated, and 11 IA chicks were studied. Animals with IA were severely undernourished by weight (43.4 +/- 4.7 v 70.3 +/- 7.6% of egg weight, P < .001) and length (15.3 +/- 1.1 v 18.1 +/- 0.9 mm tibial length, P < .001) in comparison with sham-operated ones. Their hematocrit was slightly lower, and total protein increased. Prealbumin was absent in their sera and albumin, alpha and beta globulins were significantly decreased, whereas gamma-globulin was greatly increased. Sodium, potassium chloride, urea, and glucose remained within normal limits. The lack of placenta in the avian embryo precludes any supply of nutrients by this route and the ingestion of amniotic fluid, which is protein-rich after the 13th day of incubation, when the opening of the seroamniotic connection allows albumen to be mixed with it, becomes the main source of nutrients until hatching. Obstruction of the main incoming avenue by IA induces severe malnutrition in this model which relies on this route to a greater extent than the human fetus. In spite of the obvious biological differences between the avian embryo and the human fetus, the present evidence supports the hypothesis that prenatal interruption of the amniotic fluid transit contributes to fetal undergrowth in IA.


New techniques in fetal surgery.

New techniques in fetal surgery. Optimal fetal management during and after fetal surgery has been limited by an inability to reliably monitor the fetal heart rate and temperature, and by a lack of access to the fetal circulation. In order to solve these problems, we used early third trimester fetal sheep to develop: (1) an implantable radiotelemetry device that transmits the fetal electrocardiogram and temperature, and (2) an intraosseous access technique. A miniaturized radiotelemeter was implanted subcutaneously in the axilla of four fetal sheep. Safe implantation of the radiotelemeter was technically feasible and the device reliably recorded the fetal electrocardiogram and temperature both intraoperatively and postoperatively. Although many possible routes for access to the fetal circulation have been tried experimentally and clinically for both resuscitation and blood sampling, none have proven satisfactory. We assessed the use of intraosseous access in fetal sheep (n = 6) for both infusion and blood sampling. Access with an intraosseous needle was obtained in both sheep fetuses and human fetal cadavers. Blood gas values (pH, PCO2, and PO2) obtained from the medullary cavity of fetal sheep accurately reflected peripheral venous values. Resuscitation drugs reached the fetal circulation via the intraosseous route: sodium bicarbonate elevated venous bicarbonate levels from 28.4 +/- 1.7 to 31.8 +/- 2.1 mEq/dL (P < .05); injected glucose increased venous glucose levels by 520 +/- 108 mg/dL (P < .01); and injection of calcium chloride elevated venous calcium levels from 11.8 +/- 0.7 to 15.2 +/- 2.2 mEq/dL (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)


Management of catastrophic neonatal midgut volvulus with a silo and second-look laparotomy. The case of a neonate with midgut volvulus and severe intestinal ischemia extending from the ligament of Treitz to the midtransverse colon is presented. Management consisted of abdominal silo application at the initial exploration to obviate the adverse physiological consequences of increased intraabdominal pressure from reperfusion edema of the intestine. The majority of the intestine was salvaged, and a short segment of ileum was resected. This method of treatment resulted in optimal ventilatory status, renal function, and cardiac performance. The advantages of temporary prosthetic wound coverage in selected cases of midgut volvulus include greater physiologic stability through the avoidance of "intraabdominal hypertension" and the ability to monitor the status of the intestine at the bedside.


Neonatal gastrointestinal perforations.

Neonatal gastrointestinal perforations. Neonatal gastrointestinal perforation has been associated with mortality rates of 40% to 70%. Over the past 20 years, 81 infants (46 boys and 35 girls) were treated for a gastrointestinal perforation at this institution. Perforation occurred from birth to 50 days (average, 8.2 days). Etiologies included necrotizing enterocolitis (NEC) (68%), meconium ileus (10%), and idiopathic gastric perforation (7%). Seventy-six infants underwent surgical exploration and five infants, considered too small or too sick to withstand a laparotomy, were treated with peritoneal lavage only. There were 29 deaths, an overall mortality of 36%. Ninety percent of the death occurred in patients with NEC, while all patients with gastric perforations survived. There has not been a significant improvement in survival in recent years, partly because of an increase in the proportion of NEC-related perforations. However, there is a narrowing of the mortality gap between low birth weight and normal weight infants. As the risk inherent to laparotomy in neonates is decreasing, other factors, such as the underlying etiology or the site of perforation, play a more important prognostic role.


Clinical factors affecting mortality in children with malrotation of the intestine. In children with symptoms secondary to malrotation of the intestine, a retrospective statistical study was undertaken to identify factors associated with an increased risk of mortality. Between 1964 and 1989, laparatomy was performed on 182 children. For study purposes, the children were divided into three groups. Group I included 71 patients with an obstruction only in the duodenum. The remaining 111 children, all of whom had midgut volvulus, were further divided; those without gut necrosis (79) into group II, and those with necrosis (32) into group III. One child each died in groups I and II, and 15 in group III. In all children we evaluated the relationship between mortality and age at presentation, presence of associated serious abnormalities, time from onset of symptoms to surgery, and the presence of necrotic bowel. For group III, we considered the influence of percentage of bowel resected on mortality. In these 182 children the factors associated with an increased risk of mortality were presence of necrosis (P < .0001), presence of other abnormalities (P = .0008), and younger age (P = .0084). Time from onset of symptoms to surgery was not associated with statistically increased risk of mortality. The 1% mortality noted in children without intestinal necrosis (group I and II) was related to associated abnormality. For group III the estimated probability of survival ranged from .999 for patients with 10% of intestinal necrosis to .351 for whose with 75% of intestinal necrosis, assuming the best prognostic conditions (patient older than 3 months with no associated serious abnormalities).


Gastroschisis wringer clamp: a safe, simplified method for delayed primary closure. When primary abdominal wall closure in a newborn with gastroschisis cannot be accomplished safely, placement of a reinforced Silastic silo facilitates delayed primary closure (DPC). In this report we describe our experience with the gastroschisis wringer clamp (GWC). The GWC is an autoclavable, 140-g, aluminum alloy device reminiscent of an old wringer washing machine. It consists of two apposing serrated rollers that pull the Silastic silo through a slotted base plate. This protects the intestine and converts the circular defect into a vertical slit to ease DPC. The GWC is adjusted daily on the awake newborn in the nursery and the magnitude of each adjustment is gauged by the infant's cardiac and pulmonary status. For the past 10 years we have cared for 116 newborns with gastroschisis. The average birth weight was 2,530 g (range, 1,380 to 3,300 g). Eighty-six infants (74.1%) have undergone primary closure. The remaining 30 infants (25.9%) were treated by placement of a Silastic silo and application of the GWC, forming the basis of this report. The DPC operation was performed an average of 6.7 days (range, 3 to 23 days) following the application of the silo. Extubation was usually possible prior to the DPC, with the mean length of mechanical ventilation being 3.8 days. Three patients developed serious complications including two dehiscences of the silo-fascia interface. There were no deaths in this group of 30 patients. The GWC offers many technical advantages and can be easily reversed when the infant's cardiopulmonary status deteriorates. We advocate its adoption as a method of choice in the newborn with gastroschisis who requires DPC.


Unilateral leg edema caused by abdominoscrotal hydrocele: elegant diagnosis by MRI. A 5-month-old boy presented with bilateral hydroceles since birth and right leg edema. An ultrasound of the pelvis showed a 4-cm cystic mass that was diagnosed as a teratoma or cystic hygroma. Magnetic resonance imaging was performed, which showed a dumbbell shaped contiguous, fluid filled mass extending intraabdominally through the inguinal canal from the scrotum. The cystic portion in the right iliac fossa was lying on the right iliac vessels, which were patent. A bilateral hydrocelectomy was performed, and the intraperitoneal sac was completely excised through the inguinal incision. The edema of the right leg disappeared a few days after surgery.


Cloacal exstrophy: prenatal diagnosis before rupture of the cloacal membrane. Embryologically, cloacal exstrophy is thought to result from persistence and subsequent rupture of the infraumbilical cloacal membrane during the fifth embryonic week. We report a case of cloacal exstrophy in which a prenatal diagnosis was made prior to rupture of the cloacal membrane. A routine ultrasound at 17 weeks' gestation demonstrated monoamniotic twins. One twin was normal, but the other was found to have a sacral myelomeningocele, "rocker-bottom" feet, splaying of the pubic rami, and a large cystic mass protruding from the infraumbilical anterior abdominal wall. A repeat ultrasound was performed at 22 weeks, with the same findings. At 26 weeks, further examination showed disappearance of the abdominal cyst, a small omphalocele, no demonstrable bladder, and the suggestion of prolapsed bowel inferior to the umbilical cord insertion. After delivery at 34 weeks, the abnormal twin was found to have the typical findings of cloacal exstrophy, myelomeningocele, bilateral lower limb anomalies, and extremely foreshortened small bowel. Rupture of the presumed cloacal membrane after 22 weeks in this case is inconsistent with our current understanding of the embryology of this anomaly, and should stimulate a reexamination of the current concepts. If the characteristic features are recognized, cloacal exstrophy can be diagnosed by prenatal ultrasound, permitting prenatal counseling and appropriate perinatal management.


The kidney in the fetal rat model of congenital diaphragmatic hernia induced by nitrofen. This paper explores whether there is a correlation between kidney and lung growths in an experimental model of congenital diaphragmatic hernia (CDH) induced by intragastric administration of Nitrofen (115 mg/kg) in olive oil on time-dated pregnant Wistar rats at the 9th day of gestation. For comparison we used pregnant rats treated with olive oil alone. Twenty-nine normal fetuses from 3 control rats and 24 left CDH fetuses from 6 Nitrofen rats were studied. Fetal (3.6 +/- 0.8 v 4.9 +/- 0.4 g, P < .001) and total lung (2% +/- 0.5% v 2.6% +/- 0.3% of body weight, P < .001) weights were significantly decreased in animals with CDH. Kidneys were also smaller in CDH animals although not significantly (0.7% +/- 0.1% v 0.8% +/- 0.1% of body weight, P = .05) and were also histologically immature. Regression of kidney weight on body weight for both groups yielded regression lines that were identical at analysis of covariance and all data points from the CDH group were within the control group 95% confidence limits. After converting raw data into lung/body and kidney/body weight ratios, no inverse correlation suggesting a feedback mechanism of growth regulation between both organs could be found. Since nitrofen acts through modifications of the thyroid hormone status in both dam and fetus, altered maturation of several organs should be expected although some of them, like the lung, are the leading targets. The present CDH rodent model is probably different from the human malformation in spite of the striking anatomic similarities between them.(ABSTRACT TRUNCATED AT 250 WORDS)


A rare intrapericardial mass in a neonate. We describe a rare case of a neonate born with an intrapericardial mass composed of extralobar pulmonary sequestration and a cyst of bronchogenic origin. After an uneventful delivery, this full-term newborn was noted to be grunting and indrawing. He remained tachypneic despite adequate management for bilateral pneumothoraces. Diagnostic studies showed a 3 x 3 x 4 cm diameter cystic lesion in the anterior mediastinum causing posterior-lateral displacement of the superior vena cava. The heart itself was structurally normal. Bronchoscopy and esophagoscopy failed to detect any structural abnormalities. At 3 weeks of age, sternotomy and resection of the lesion was performed. The mass was clearly intrapericardial and consisted of sequestrated pulmonary tissue with a unilocular mucus filled bronchogenic cyst. Small systemic tributaries fed the lesion from the posterior-superior aspect. There was no connection with the heart or great vessels. Postoperative recovery was uneventful.


Rhabdomyosarcoma arising within congenital pulmonary cysts: report of three cases. Over the past 9 months, three cases of primary pulmonary rhabdomyosarcoma have been treated at British Columbia Children's Hospital. Two patients (aged 24 and 37 months) presented with spontaneous pneumothoraces and had cystic changes in the affected lung on chest radiograph. The third patient (aged 42 months) was evaluated for chronic cough, fever, and failure to thrive. Chest x-ray showed a large mass in the left lower lobe as well as mediastinal adenopathy. All three of these lesions originated within congenital lung cysts, one a peripheral bronchogenic cyst and the others cystic adenomatoid malformations. This report suggests that there is a significant risk for the development of rhabdomyosarcoma within malformed pulmonary tissue.


Extracellular fluid and total body water changes in neonates undergoing extracorporeal membrane oxygenation. After being placed on extracorporeal life support (ECLS), newborn patients typically weight 5% to 30% more than their birthweight. Recovery and eventual decannulation from ECLS is associated with a return to baseline weight or birthweight values after a pronounced diuresis. It has been assumed that the increases in weight in these patients are due to increases in extracellular fluid (ECF) and total body water (TBW). This study was undertaken to prove or disprove this hypothesis. ECF space was measured using the compound sodium bromide and TBW was determined with the use of deuterium oxide (nonradioactive heavy water). Fluid compartment measurements were made prior to the institution of ECLS, immediately after placement on bypass, approximately every other day while on bypass, and a final measurement was made once the patient was off bypass. Sodium bromide concentration was analyzed by high-pressure liquid chromatography, and deuterium oxide concentration was measured by the falling drop method. Eight newborns with respiratory failure were placed on either venoarterial (4 patients) or venovenous (4 patients) ECLS for an average of 106 hours (range, 71 to 219 hours). Pre-ECLS TBW was high in the neonates (87% of total body weight v the normal of 75% to 80%). Mean values for each fluid compartment were corrected for the additional volume of the bypass circuit when the patient was on bypass. ECF increased immediately after the institution of ECLS; however, both ECF and TBW decreased during the bypass run, and post-ECLS levels of ECF and TBW were similar to those found prior to ECLS.(ABSTRACT TRUNCATED AT 250 WORDS)


Resection of the primary tumor is appropriate for children with stage IV-S neuroblastoma: an analysis of 37 patients. Current recommendations for treatment of children with IV-S neuroblastoma (NB) indicate that "supportive care is the cornerstone of therapy" and resection of the primary tumor is not mandated. The presentation and clinical management of 37 IV-S NB patients from three pediatric oncology centers were retrospectively reviewed. The 22 boys and 15 girls presented at an average age of 107 days (range, 4 to 616 days). Primary tumor sites were identified in the adrenal gland in 19 children, the thorax in 5, the retroperitoneum in 4, and 1 each in the pelvis and kidney. At the time of presentation, metastatic disease was documented in the liver (27), bone marrow (19), skin (7), and regional lymph nodes (7). Massive hepatomegaly (below the umbilicus) was demonstrated in 18 patients. Twenty-eight children (76%) have survived on average 90 months following diagnosis. Eight patients (22%) died; six of disease and two of complications of therapy (mean, 9.6 months). One child was lost to follow-up. Only 3 of the 37 patients (8%) were managed solely by supportive care and all are alive. Extirpation of the primary tumor was accomplished in 24 individuals (65%). Twenty patients underwent excision at diagnosis and four had delayed resection with few postoperative complications and no deaths related to resection. One death resulted from progression of disease in a child who had tumor removal. Chemotherapy as a single treatment or in combination with radiation was used in 10 children with three children surviving (30%).(ABSTRACT TRUNCATED AT 250 WORDS)


Improved outcome utilizing spinal anesthesia in high-risk infants. The development of apnea following general anesthesia in high-risk infants (less than 60 weeks postconceptual age) has been reported up to 37%, prompting the routine admission of these children following minor surgical procedures. One hundred forty high-risk infants (American Society of Anesthesiologists category greater than or equal to 2) were prospectively evaluated after undergoing surgical procedures normally performed as outpatients in low-risk babies. All patients had spinal anesthesia for their operations. The mean gestational age for these infants was 30.8 +/- 3.7 weeks (minimum, 24 weeks) with a mean birth weight of 1,466.0 +/- 638.8 g. The mean postconceptual age and weight at the time of surgery were 44.8 +/- 7.8 weeks and 3,336 +/- 1,242 g, respectively. Difficulty in administering the spinal anesthetic occurred in 6 cases (4.2%). Postoperative complications occurred in 5 children (3.8%). They were: postoperative fever (2), transient bradycardia (2), and apnea (1). The four cases of postoperative fever and bradycardia were insignificant and required no medical intervention. The single case of apnea occurred in a premature infant who received a supplemental dose of intravenous midazolam. Length of operation in these cases ranged from 15 minutes to 95 minutes (mean, 53 minutes), with two incidents of inadequate anesthesia occurring in this cohort. Mean duration of anesthesia was 146 minutes (range, 50 to 240 minutes) and was directly dependent on dosage administration of the agents. These data indicate that the use of spinal anesthesia in high-risk infants is safe and effective for surgical procedures generally performed as outpatients (3.0% minor complication rate, 0.8% major complication rate).(ABSTRACT TRUNCATED AT 250 WORDS)


Growth hormone reverses impaired wound healing in protein-malnourished rats treated with corticosteroids. Corticosteroid (CS) administration amplifies the inhibitory effect of protein malnutrition (PM) on wound healing. Abdominal surgery in protein malnourished patients receiving corticosteroids (eg, advanced malignancy, transplant recipients) may be complicated by wound dehiscence or anastomotic breakdown. Although preoperative parenteral nutrition can reduce the incidence of these complications, this is not possible in patients requiring urgent surgical intervention. In a previous report we demonstrated that postoperative growth hormone (GH) administration could restore normal wound healing in PM rats. This study evaluates the effect of GH on wound healing in PM rats treated with CS. Forty-eight female Sprague-Dawley rats weighing 180 to 210 g were divided into four groups: (1) normally nourished; (2) PM only; (3) PM + CS; and (4) PM + CS + GH. PM rats (groups 2 to 4) received 5.5% protein chow every other day for 8 weeks. Control rats (group 1) received 23.4% protein chow for the same duration. Group 3 and 4 rats received prednisolone (2 mg/kg, intramuscularly) during the last 3 weeks of PM. All animals underwent precise 5-cm midline celiotomies. Postoperatively, rats in all groups were given 23.4% protein chow. Group 3 and 4 rats continued to receive CS postoperatively. Group 4 rats were given GH (0.5 mg/d, intraperitoneally) postoperatively for 5 days. Wound testing was performed on the 6th postoperative day after removal of the sutures. A balloon inserted into the peritoneal cavity through the vagina was gradually inflated. The pressure at which the wound disrupted was recorded as the wound bursting strength.(ABSTRACT TRUNCATED AT 250 WORDS)


Cultured epidermal autografts: a life-saving and skin-saving technique in children. The recent more widespread availability of cultured keratinocytes has increased their clinical applicability in pediatric surgical problems. In life threatening burns (3 patients) and in elective procedures (3 patients) we have used sheets of cultured epithelial autografts. Body surface area affected ranged from fifteen to 85%. Five patients were successfully treated in one grafting session and one required four sessions. Take of the cultured keratinocytes ranged from 75% to 95%. Follow-up as long as 30 months has shown the skin to be comparable to if not superior to conventional split thickness grafts. The use of cultured keratinocytes allows wound coverage without expansion of the affected body surface area seen with conventional split-thickness skin grafting. Although there is an initial delay in the preparation of the grafts, the overall results have been excellent and suggest the more frequent use of this method.


Early induction of IL-6 in infants undergoing major abdominal surgery. Cytokines are immunoregulatory molecules that are important mediators of the host response to stress and infection. Infants and children undergoing major surgery are particularly at risk of developing sepsis and have altered metabolic responses to surgical stress compared to adults. We have investigated the temporal sequence of cytokine responses in six infants (mean age, 11 +/- 7.5 months) undergoing pull-through operation for Hirschsprung's disease and correlated them with hemodynamic and biochemical parameters. Tumor necrosis factor (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6) were measured by ELISA preoperatively, intraoperatively (hourly), and 24 and 48 hours postoperatively. IL-6 levels increased significantly in all cases within 2 hours of commencement of the operation (P less than .01) and were maximal 24 hours postoperatively. No significant changes in IL-1 beta levels (mean range, 70 to 110 pg/mL) were seen in these patients. TNF levels were undetectable (less than 20 pg/mL) throughout the study. Cortisol levels were increased in all patients during operation. Serum C-reactive protein levels were first detected 24 hours postoperatively and continued to increase 48 hours postoperatively. Hemodynamically, heart rate increased during the first 3 hours of operation and correlated with increase in IL-6 levels. Blood pressure and temperature changes did not correlate with cytokine levels. This study identifies IL-6 as the earliest detectable cytokine response associated with major surgery in infants. It also suggests that IL-6 can be unregulated, independently of other cytokines, in response to surgical stress.


Experience with a nurse practitioner program in the surgical department of a children's hospital. Manpower limitations are occurring in residency programs because of fewer residency positions and increasing governmental regulations. This limitation prompted the development of a program to utilize pediatric nurse practitioners (PNPs) in our Department of Surgery. Two began in September 1989. Their role was similar to that of the junior resident and included collaborative management of patients, admission evaluations, discharges, and a variety of procedures. The impact of this program was evaluated by questionnaire to attending surgeons, house staff, and parents. There were 123 surveys mailed (12 attending surgeons, 46 residents, 65 parents). The overall response rate was 51% (100% attending surgeons, 57% residents, and 38% parents). Only two of the attending surgeons had previous experience working with a PNP. All attending surgeons were enthusiastic about the PNP role in managing their patients and felt the PNP had decreased the workload of the resident. Eighty-three percent did not feel the PNP interfered with resident learning; 17% were undecided. Eleven of 12 felt the PNP had helped communication between them and their patients; one was undecided. The resident responses were assessed by level of training. Among senior residents, 82% felt the PNP had decreased the workload of the junior resident and 91% viewed the PNP as a valuable resource, whereas 87% of the junior residents felt the PNP decreased their workload and 100% felt the PNP was a valuable resource. None of the residents felt the PNP interfered with their learning and 73% of the junior residents and 55% of the senior residents felt the PNP contributed to their learning.(ABSTRACT TRUNCATED AT 250 WORDS)


The splenic snood: an improved approach for the management of the wandering spleen. A wandering spleen is in constant danger of torsion and infarction. Splenectomy, the traditional treatment, leaves children in danger of postsplenectomy sepsis. Three children with wandering spleens were treated by a new splenopexy technique, the splenic snood. After detorsion, the spleens were wrapped in polyglycolic mesh and anchored by the mesh subdiaphragmatically in the left upper quadrant. All have retained their spleens which have remained where anchored up to a 4-year follow-up. The simplicity and technical ease of the splenic snood operation recommend it as an improved method to avoid splenectomy and safely normalize intraabdominal anatomy in the management of the wandering spleen.


Response to Haemophilus influenzae type B conjugate vaccine in children undergoing splenectomy. Asplenic children are at increased risk for serious infection with polysaccharide encapsulated bacteria including Haemophilus influenzae type b (HIB), Streptococcus pneumoniae, and Neisseria meningitidis. Immunization with polysaccharide vaccines is recommended for children undergoing splenectomy. In 1987 a new more immunogenic HIB vaccine was licensed in the US to replace the pure HIB polysaccharide vaccine that was licensed in 1985. This polysaccharide-conjugate vaccine consists of the HIB polysaccharide linked to a protein carrier, diphtheria toxoid. Therefore, we evaluated the immune response of children undergoing splenectomy to HIB-conjugate vaccine. Thirteen children (7 with Hodgkin's disease, 4 with idiopathic thrombocytopenia, 2 with hereditary spherocytosis) aged 3 to 19 years were immunized with HIB-conjugate vaccine prior to splenectomy and serum was obtained following splenectomy. In addition, 15 healthy control children aged 2 to 14 years were immunized with the pure polysaccharide HIB vaccine for comparison. The patients undergoing splenectomy who received the HIB-conjugate vaccine had a geometric mean IgG anti-HIB antibody concentration of 48,106 ng/mL versus 10,786 ng/mL for the control patients who received the pure polysaccharide vaccine (P = .01). The presumed protective level of antibody is 1,000 ng/mL and all children were well above this concentration. Therefore, we propose that children undergoing splenectomy be immunized with an HIB-conjugate vaccine.


Successful splenorenal shunt for emergent control of variceal bleeding in a small child. A 8.6-kg, 10-month-old boy with idiopathic cavernous transformation of the portal vein developed variceal hemorrhage refractory to nonoperative management. A distal splenorenal shunt was performed while the bleeding was controlled with balloon tamponade. Hemorrhage was successfully controlled with no recurrent bleeding and the shunt remains patent at 1 year of follow-up.


The risk of abdominal operations in children with ventriculoperitoneal shunts. Ventriculoperitoneal (VP) shunts are the operations of choice for patients with hydrocephalus in most pediatric hospitals. Children with VP shunts frequently undergo abdominal operations unrelated to their shunts, which might lead to shunt infections or to malfunctions related to adhesions. Although prophylactic antibiotics are usually used in this setting, there are few data to support their use, or to assess other risks to the shunt from the abdominal procedures. Consequently, we reviewed the records of 37 children with VP shunts who underwent a total of 44 abdominal operations. In 8 cases, the genitourinary (GU) tract was opened (ureteral reimplantation, bladder augmentation, nephrectomy), whereas in 18 patients the gastrointestinal (GI) tract was opened (appendectomy, gastrostomy, small/large bowel resection). In 18 operations neither GI nor GU tract was opened (lysis of adhesions, herniorrhaphy, orchiopexy). Antibiotic coverage was highly variable: 9 received no antibiotics, 9 received antibiotics only postoperatively, 4 were given antibiotics only preoperatively, and in 22 cases antibiotics were given both preoperatively and postoperatively. One shunt that was involved in a periappendiceal abscess was exteriorized and later successfully replaced. In the remaining cases, no episodes of shunt infection or malfunction occurred in 1 to 10 years of follow-up. Likewise, no abdominal cerebrospinal fluid pseudocysts formed as a result of abdominal adhesions. These data demonstrate that children with VP shunts can safely undergo abdominal operations, even when the GI or GU systems are opened, with minimal risk of shunt infection or malfunction. Rigid protocols of prophylactic antibiotics cannot be supported by this series.


Mycotic thromboaneurysmal disease of the abdominal aorta in preterm infants: its natural history and its management. Five infants with mycotic complications of umbilical artery catheterization were evaluated with abdominal ultrasound and followed serially to document their natural history. Methicillin-resistant Staphylococcus aureus was always the infecting organism. There were one female and four male infants and they weighed between 900 and 1,200 g at birth. While two of the catheters were positioned in the abdominal aorta, three were located above the diaphragm. The predominate signs and symptoms included: thrombocytopenia, unexplained anemia, renal failure, hypertension, and embolic phenomena to the toes. Real-time ultrasound always proved sufficient for diagnosis. Serial studies detected the initial aortic thrombosis in three patients and accurately documented its progression to aneurysmal disease over 10 days in one patient and 17 days in another. Three of the infants were diagnosed with aneurysms at their initial examination. Of the five patients, three were treated nonoperatively and died of complications of their aortic disease. One patient was discovered at operation to have necrotic ischemic intestine. Aortic repair was postponed and he died of septic complications. The remaining patient underwent a PTFE interposition graft and survived for 6 months, dying of pulmonary failure with autopsy confirmed graft patency.


Mucosal morphology in isolated bowel segments: importance of exposure to luminal contents. An isolated bowel segment (IBS) is a loop of intestine that has been freed from its mesenteric attachment after the development of vascular collaterals between the antimesenteric surface of the gut and the host organ. Surgical creation of such artificially vascularized isolated bowel segments is of interest to researchers for a variety of studies, and may be useful in the treatment of short bowel syndrome, allowing longitudinal division of the remaining small bowel to double its length. We created four surgical variants to study the ability of the collateral blood supply to maintain mucosal integrity in the presence or absence of normal luminal contents. In all groups, a collateral blood supply was created in a 5- to 7-cm segment of adult rat jejunum by hepatoenteropexy (Iowa model II). In Thiry-Vella (T-V) and isolated bowel segment (IBS) rats, this segment was exteriorized at both ends to exclude luminal contents. Control and IBS in continuity (IBS-C) loops were left in continuity. The mesentery of IBS and IBS-C rats was divided 5 weeks later, leaving the experimental segment entirely dependent on the collateral circulation. All animals were harvested at 7 weeks after the initial surgery. Tissues were analyzed for mucosal weight, protein content per centimeter of bowel, length of villi, depth of crypts, DNA content, and sucrase activity. We found that segments retaining luminal continuity had significantly higher mucosal weight and DNA content per centimeter of bowel compared with exteriorized loops.


Laparoscopic cholecystectomy in children: initial experience and recommendations. Our initial experience with laparoscopic cholecystectomy in children and the modification of techniques required for pediatric surgical patients is reported. Six children aged 6 to 17 years underwent laparoscopic cholecystectomy for symptomatic cholelithiasis. All patients had biliary colic and did not require concomitant intraabdominal surgical procedures. Average operative time was 89 minutes; none were converted to open cholecystectomy. One patient returned home the evening of surgery, two patients were discharged the following morning, and two patients were discharged 2 days following the procedure because of their distance from home. There were no complications. All patients have remained asymptomatic on follow-up of 1 to 5 months. Based on this initial experience, several changes in the technique as reported in adults are recommended. Due to the softness and laxity of the anterior abdominal wall, an infraumbilical incision for the 10-mm camera trocar is more cosmetically acceptable and just as efficient. There is a smaller intraabdominal space with which to work, tempting one to overinflate the abdomen for better visualization. Care should be taken to ensure that the intraabdominal pressure does not exceed 15 mm Hg despite the small volumes required to do so. Placement of the second epigastric incision is more inferior and lateral than the standard recommendation for adults. The cystic duct must be controlled as early as possible in the operative course to prevent egress of stones from the gallbladder into the common duct. In one patient, these migrating stones were milked back into the gallbladder and a second clip placed.


The atonic baggy rectum: a cause of intractable obstipation after imperforate anus repair. Three children with successful imperforate anus repairs had chronic, intractable obstipation and recurrent fecal impaction refractory to diligent medical therapy. All had massive stool-filled rectums up to 14 cm in diameter on abdominal radiographs. They responded well to resection of the baggy atonic rectum with low anterior anastomosis. The massively dilated atonic rectal pouch in some children with repaired imperforate anus can demonstrate abnormal motility characterized by poor peristalsis and propulsion. This results in recurrent obstipation, impaction, and soiling refractory to the usually successful medical management.


Sacrococcygeal teratoma: the experience of four decades. To determine the extent of progress in the treatment of sacrococcygeal teratomas (SCTs), we evaluated the experience with 73 patients over 40 years. The medical records of the children were reviewed for demographics, histology, clinical course, and outcome. Therapy differed depending on the type of SCT, histology, and decade of diagnosis. The female:male ratio was 4.2:1 and did not vary significantly with the histology of the tumor. Fifty-seven patients presented with benign disease. There were five recurrences in this group, only one of which did not have an initial coccygectomy. One tumor, originally thought to be benign with immature elements, had a local recurrence at 7 months, 10 months, and 16 months after the original operation and was discovered to have embryonal carcinoma with nodal involvement. This child was treated with chemotherapy and is disease-free at 7 years. Morbidity in the benign group included 3 postoperative wound infections. Three infants died, one before operation with beta-hemolytic Streptococcus sepsis. Two neonates died in the early postoperative period, one on day 1 with a ruptured subcapsular hematoma of the liver, and the second on day 2 with disseminated intravascular coagulation/sepsis. Benign SCT occurs at a younger age than malignant tumors. The average age of presentation of benign tumors is 20 days versus 468 days in children with malignant disease. The technique of wide resection of benign lesions with coccygectomy is helpful in preventing recurrence and has changed little over the last four decades. Malignant SCT occurred in 16 children (22%).(ABSTRACT TRUNCATED AT 250 WORDS)


Prognostic factors and outcome in patients 21 years and under with colorectal carcinoma. This study aims to identify significant predictors of survival in pediatric and adolescent colorectal carcinoma. We retrospectively analyzed our experience with 29 histologically verified cases, of which 20 were resected for cure. Variables analyzed as predictors of survival included: (1) resectability, (2) regional nodal involvement, (3) depth of invasion, (4) grade, and (5) interval from symptom onset to diagnosis. Signet ring or anaplastic lesions were considered high grade. Survival curves were generated on both the overall group and those resected for cure. Multivariate analysis was performed on the overall group. The median age at diagnosis was 19 years (range, 10 to 21). Median follow-up in survivors was 4.7 years. Signet ring tumors occurred in 45% and another 24% were poorly differentiated. Seventy-six percent presented with regional lymph node metastases. The median survival for the overall group was 16 months, whereas that for those undergoing complete resection was 33 months. In patients undergoing resection for cure, grade (P = .005), regional nodal involvement (P = .007), and depth of invasion (P = .03) were significant predictors of outcome in univariate analysis. In the overall group these variables as well as resectability and distant metastases were significant in univariate analysis. In multivariate analysis high-grade lesions and lymph node involvement were highly correlated, as were resectability and metastases. Thus, either variable (but not both) of each pair added information to the multivariate model. In patients resected for cure, positive nodes or high histological grade became the only significant predictors of survival.(ABSTRACT TRUNCATED AT 250 WORDS)


Transhiatal esophagectomy and colonic interposition for caustic esophageal stricture. From January 1986 through 1990, 70 children (42 boys, 28 girls) with esophageal stricture resulting from ingestion of caustic potash underwent simultaneous esophagectomy and colonic interposition utilizing the transhiatal esophageal approach. At the time of the procedure, their ages ranged from 14 months to 6 years (mean, 3.2 years). Thoracotomy was needed in one patient due to accidental injury to the tracheal during esophageal mobilization. There were 3 deaths from respiratory failure. Otherwise, morbidity was low, and there were satisfactory long-term functional results. The use of isoperistaltic left colon based on both ascending and descending branches of the left colic vessels resulted in survival of all grafts. End-to-side esophagocolic anastomosis decreased the incidence of both postoperative leak (2 instances) and late stenosis (1 case needed surgical revision). Construction of a length of colonic graft equal to the gap between the esophagus above the stricture and the stomach and fixation of the graft to the edge of the esophageal hiatus reduced the incidence of late colonic redundancy in the chest; this did occur in 4 cases but was not associated with dysphagia. Routine pyloroplasty and anterior cologastric anastomosis to the gastric antrum contributed to the absence of gastrocolic reflux and peptic ulceration in this series.


Transventricular dilation for critical aortic stenosis in neonates. Critical aortic stenosis (CAOS) is not compatible with life when the ductus arteriosus closes. We have treated 11 consecutive cases with isolated CAOS. Symptom presentation was in the early neonatal period and diagnosis was made noninvasively at a mean age of 4 days. All were operated on with transventricular dilation (TVD) at a mean age of 4.7 days. There was no early mortality. There were two late deaths due to fibroelastosis. Both had the smallest aortic anulus diameter (5 mm). Two other patients had aortic root replacement, one at the age of 6.5 weeks due to intractable heart failure, and the other at the age of 3 months due to increasing gradient. In these two cases elective surgery was made possible by a successful TVD in the early neonatal period. TVD in this material was not associated with any early mortality, which makes this procedure a good alternative in the treatment of CAOS.


Prolonged extracorporeal support for nonneonatal respiratory failure. Extracorporeal membrane oxygenation (ECMO) is effective for newborns with pulmonary failure unresponsive to conventional therapy. However, ECMO for the older child and adult has been controversial and not widely utilized. Over 4 years, 24 patients (aged 4 months to 16 years; 11 boys, 13 girls) underwent venoarterial ECMO (duration, 7 to 19 days) for respiratory failure. The diagnoses were: viral pneumonia (7), hydrocarbon aspiration (6), sepsis with adult respiratory distress syndrome (ARDS) (2), bacterial pneumonitis (2), tracheal stenosis (1), bilateral pulmonary contusion (1), diaphragmatic hernia with ARDS (1), ketoacidosis with ARDS (1), pulmonary artery injection of hydrocarbon (1), drowning (1), and epiglottis with barotrauma (1). Pre-ECMO blood gas ranges (and means) were PO2 18 to 65 (46), and PCO2 47 to 112 (65). Nineteen patients received dopamine, dobutamine, or other inotrope for associated cardiac and/or renal failure. Cannulation for ECMO was through neck or groin vessels in 17, and sternotomy in 7. ECMO flow rates were 150 to 250 mL/kg/min, to maintain PO2 greater than 100 and PCO2 less than 40. Nine patients (41%) survived ECMO, with eight long-term survivors, (4 hydrocarbon aspiration or injection, 1 pulmonary contusion, 1 viral pneumonia, 1 ARDS, 1 barotrauma), three of whom have mild neurological deficit. All patients with sternotomy, and 8 of 15 with neck and/or groin cannulation, required 1 to 5 explorations for hemorrhage while on ECMO. All survivors had primarily pulmonary failure; patients with combinations of pulmonary, cardiac, and renal failure did not survive. ECMO can be life-saving in the child with isolated pulmonary failure, but its efficacy in patients with multiorgan failure is uncertain.


Surgical complications and procedures in neonates on extracorporeal membrane oxygenation. We report our experience from May 1985 to January 1991 with surgical complications and procedures performed in neonates on extracorporeal membrane oxygenation (ECMO) (218 venoarterial and 7 venovenous bypass). Eleven children older than 1 month were excluded. Total complications were 96 in 67 patients and included: bleeding (37), problems with initial cannula placement (17), thrombus formation (15), hemothorax, pneumothorax, or effusions (11), mechanical problems (11), and miscellaneous (5). Forty-eight procedures were performed in 37 patients while on ECMO. These were recannulation or reposition of cannulas (14), tube thoracostomy (11), cardiac surgery (6), cardiac catheterization (4), repair of congenital diaphragmatic hernia (5), thoracotomy (4), and others. Twenty-eight complications occurred in 15 of the 27 patients who died. Mortality rate was 12% for the entire group. Primary causes of death were hypoplastic lung (11), cardiac (8), sepsis (4), intraventricular hemorrhage (2), and pulmonary hypertension (2). No deaths were due solely to complications except for the two patients with intraventricular hemorrhage. Mortality in neonates who had complications while on ECMO was significantly higher (P less than .005) than in patients without complications. Hemorrhagic and thoracic complications were associated with higher mortality (P less than .001). Mortality was not affected by mechanical problems, thrombus formation, or catheter-related problems. While on ECMO cardiac defects, diaphragmatic hernia, lobar emphysema, and other conditions can be safely corrected. The use of echocardiography to position the cannulas, better control of coagulation factors and improvement in equipment may ultimately decrease complications.


Echocardiography in the preoperative evaluation of vascular rings. Vascular rings may produce tracheal and/or esophageal compression in infants and children. Traditionally recognized fluoroscopically, the exact anatomy of the ring and appropriate surgical correction are determined intraoperatively. The role of preoperative echocardiography was examined. Twenty patients with symptomatic vascular rings were evaluated preoperatively with echocardiography at this institution. Their ages ranged from 10 days to 11 years (mean, 17 months). There were 9 boys and 11 girls. Most (17/20) presented with respiratory symptoms in the first year of life, although in 3 patients dysphagia was the primary complaint (at birth, 4 months, 9 years). All underwent initial evaluation with a barium esophagogram prior to the echocardiogram. Surgical correction was subsequently performed and the exact anatomy identified. All barium esophagograms were interpreted prospectively as demonstrating a "vascular ring." Although often suspected fluoroscopically, the actual type of ring was correctly identified by echocardiogram in all cases including determination of the dominant arch and associated anomalies. The types of vascular rings included double aortic arch (10), right aortic arch with left ligamentum arteriosum and/or aberrant left subclavian artery (6); aberrant right subclavian artery (2), and pulmonary artery sling (2). Barium esophagogram remains the best screening test for children in whom a vascular ring is suspected. However, echocardiography is a useful noninvasive complementary examination to confirm the diagnosis, clarify anatomy, and exclude other major intracardiac pathology prior to surgical correction.


Pericardial flap interposition for the definitive management of recurrent tracheoesophageal fistula. From 1974 to 1988, six children with fistula recurrence following primary tracheoesophageal fistula (TEF) repair have been managed at our hospital. Reclosure of the fistula with pleural flap interposition was used as the initial corrective procedure in five patients, with an 80% incidence of second TEF recurrences. Due to these discouraging results, we have abandoned this technique and instead favor fistula reclosure with interposition of a pedicle of vascularized pericardium between the esophageal and tracheal suture lines. The pericardial pedicle is easy to mobilize, effectively isolates the tracheal and esophageal suture lines, and eliminates the often difficult task of finding sufficient pleural tissue for fistula interposition in small infants. Furthermore, the vascularized pedicle serves as a template for the ingrowth of neomucosa from the existing esophageal mucosa should an anastomotic leak occur. Since adopting this approach, we have used this technique on four children, three of whom had second recurrences after pleural interposition, and have had no evidence of recurrent fistula formation at follow-up ranging from 2 to 6 years. With at least a 20% incidence of second recurrences reported following conventional management with fistula closure and pleural interposition, we believe use of a pericardial flap in the management of the recurrent TEF is the most appropriate surgical procedure.


Delayed primary anastomosis for esophageal atresia: 18 months' to 11 years' follow-up. In 1977 we started treating babies with isolated esophageal atresia by delayed primary anastomosis and in 1981 reported our early experience in five cases treated between 1977 and 1979. Since 1979, 11 further consecutive cases have been managed by initial gastrostomy followed by delayed primary esophageal anastomosis. Their mean gestation was 35 weeks (range, 28 to 40 weeks) and mean birth weight was 2,040 g (range, 1,140 to 2,720 g). The esophageal gap between the two ends when assessed initially at fluoroscopy ranged from 2.2 to 4.5 cm (mean, 3.2 cm). Age at delayed primary anastomosis ranged from 6 to 20 weeks. Anastomotic leak occurred in three babies in the immediate postoperative period and all were successfully managed conservatively. Eight of the 11 patients developed anastomotic strictures; seven cases required 1 to 5 esophageal dilatations. One patient who did not respond to multiple esophageal dilatations required resection of an esophageal stricture. One patient died at 15 months of age of unrelated causes. The 10 surviving patients have been followed-up from 18 months to 11 years. At follow-up, seven patients were eating normally. Three patients had swallowing difficulties and all three were found to have esophageal strictures on barium swallow, two of them also had gross esophageal reflux and hiatus hernia. The height and weight in the 10 patients varied from 3rd centile to 75th centile. Delayed primary anastomosis is feasible in cases of isolated esophageal atresia and the patient's own esophagus is the best. A more aggressive approach should be applied to gastroesophageal reflux in these patients.


Repair of long tracheal defects with cryopreserved cartilaginous allografts. Tracheoplasties with various autografts (cartilage, periosteum, pericardium) have been used in the treatment of long-segment tracheal stenosis. Previous studies have shown that cartilage allografts survive transplantation on a long-term basis in various sites of the body. In this study we set out to determine if cryopreserved cartilage and cryopreserved tracheal allografts would survive when used to cover tracheal defects in animals. A rectangular defect (2.8 +/- 0.3 cm long and incorporating 50% of tracheal circumference) was created in the thoracic trachea of 18 piglets. The defect was covered with the excised tracheal segment in 6 (group A, control group), with a cryopreserved tracheal allograft in 6 (group B), and with a cryopreserved cartilage allograft harvested from the scapula in 6 (group C). The allografts were cryopreserved, by a standard slow-freezing technique, at -80 degrees C for more than 21 days. All animals survived the grafting procedure and were killed after 2 months. None had signs of airway obstruction. Using the trachea above the defect as the standard, the mean sagittal narrowing of the airway in the repaired trachea was 0.4 mm in group A, 0.7 mm in group B, and 0.6 mm in group C; the coronal diameter in normal and grafted trachea was similar. The lumen of all grafts was lined by regenerating respiratory epithelium, and cilia were seen in many. Some cartilage was reabsorbed in group A and B but cartilage islands were present in all. In group A, reabsorption of cartilage was minimal. These findings suggest that segments of trachea or cartilage allografts can be cryopreserved, stored, and, subsequently, used when necessary for tracheoplasty.


Severe tracheomalacia associated with esophageal atresia: results of surgical treatment. This study reviews our experience from 1977 to 1991 with 32 children born with esophageal atresia and tracheoesophageal fistula (EA-TEF) who later underwent surgery for severe tracheomalacia. Indications for surgery included dying spells (21), inability to extubate the airway (nasotracheal tube 5, tracheotomy 3), and recurrent pneumonia (3). Diagnosis was confirmed by chest x-ray, esophagogram, and bronchoscopy. Aortopexy was performed in 31 of 32 children; a splint without aortopexy was used in one older girl. Splinting was also necessary in two of the 31 at the initial operation, when aortopexy failed to prevent tracheal collapse. There were four initial failures. Currently, 29 children are well (median follow-up, 6.6 years). Two have a tracheostomy in place, and one, who had a vascular ring divided after aortopexy, died at home of unknown cause 1 month later. These findings indicate that aortopexy provides long-term relief of severe symptoms of tracheomalacia associated with EA-TEF in almost all affected children. When aortopexy fails, the insertion of an airway splint may succeed; otherwise, tracheostomy is necessary.


The balloon posterior tracheal split: a technique for managing tracheal stenosis in the premature infant. Congenital tracheal stenosis (CTS) in the premature infant almost invariably leads to death for lack of effective reconstructive techniques. We hypothesized that the complete or near complete cartilaginous rings of CTS have a weak point in the posterior portion. Aggressive balloon dilation would result in a posterior longitudinal disruption of the trachea, and an expanded tracheal wall would be created after an appropriate period of endotracheal stenting. Three premature infants with multiple anomalies and CTS were treated with endoscopic posterior tracheal splitting, dividing the trachea as predicted. Although two died of complications of congenital heart disease 2 weeks after the procedure, the third child is alive and well at 9 months of age without airway symptoms. The posterior tracheal wall also split when we performed the procedure in a fresh cadaveric CTS patient. We believe that balloon dilation may prove to be a valuable technique in the treatment of premature infants with congenital or acquired tracheal stenosis and/or in children with such complex diseases that major surgery is precluded.


Acquired lobar emphysema (overinflation): clinical and pathological evaluation of infants requiring lobectomy. Acquired lobar "emphysema" (overinflation) (ALE) is an increasingly recognized complication of advanced bronchopulmonary dysplasia (BPD). To refine current concepts regarding patient management and pathogenesis, we examined clinical and pathological features of six infants with ALE who did not have obstructing intraluminal lesions and who underwent lobectomy after failing nonoperative management. All had severe neonatal respiratory distress and required prolonged ventilatory support (average, 2 months) with peak inspiratory pressures greater than 30 mm Hg and 100% oxygen. ALE developed between 3 weeks and 20 months of age (median, 5 months), with lobar hyperinflation, atelectasis, and mediastinal shift. Selective bronchial intubation provided only transient benefit. Videobronchoscopy demonstrated no intraluminal obstructing lesions in five patients. In one child, ALE became clinically apparent only after laser excision of an endobronchial cicatrix. All infants had bronchomalacia with the involved lobar bronchus being most severely affected. Ventilation-perfusion scans demonstrated severe impairment of both ventilation and perfusion in the involved lobes. The decision to perform lobectomy was based on clinical parameters and failure of non-operative management. After lobectomy, all children dramatically improved. However, only three of six were alive 2 to 3 years later; one infant died of unrelated causes at 6 weeks; and two died of progressive respiratory insufficiency 13 and 24 months postlobectomy. Microscopic evaluation of the lung demonstrated findings of late-stage BPD with peribronchial and interstitial fibrosis, parenchymal overinflation, and alveolar septal disruption.(ABSTRACT TRUNCATED AT 250 WORDS)


Reduced-size lung transplantation from adult to neonatal sheep. Lung transplantation continues to be limited by donor availability. This shortage is particularly acute in the pediatric population. A model was developed in sheep to simulate human pulmonary transplantation from adults into newborns. Pulmonary allografts were performed in 8 neonatal lambs (less than 10 days old) weighing between 2.5 and 5 kg. Unrelated adult sheep donors were used (weighing 55 to 82 kg). The recipient body weight was approximately 6% that of the donor, but ranged from 4% to 8%. Ipsilateral or contralateral upper lobe allografts were used, although the latter required inversion prior to implantation. All venous anastomoses utilized left atrial cuffs. The pulmonary arterial and bronchial anastomoses were constructed end-to-end. Following implantation the lobes were further contoured to fit within the recipient hemithorax using a linear surgical stapler. Animals were immunosuppressed with cyclosporine. Two animals died 1 week postoperatively but the remaining six survived 1 to 5 months. Postoperative lung scans at 10 to 14 days confirmed satisfactory ventilation and perfusion of the allografts. All vascular anastomoses were intact at postmortem examination. Primary bronchial healing accomplished without an omental wrap. We conclude that successful lung transplantation can be performed from adult donors into neonatal recipients. Preservation of the maximal arterial and venous length during native pneumonectomy is essential to allow matching of the vascular cuffs. Short donor lobar bronchi may be responsible for the reliable primary healing. Improved immunosuppression will be required to assess long-term function and growth of these reduced-size allografts.


Experience with a total muscle-sparing approach for thoracotomies in neonates, infants, and children. We have adopted a total muscle-sparing technique for thoracotomies in infants and children. The technique preserves the latissimus dorsi and serratus anterior muscles and provides excellent exposure for most thoracic and mediastinal operations. Thirty-two such procedures have been performed with only one complication, a small wound seroma. Use of this technique may not only decrease postoperative pain and splinting, but may decrease the incidence of scoliosis and muscle dysfunction found in children having undergone thoracotomies as infants.


Biology of fetal wound healing: collagen biosynthesis during dermal repair. The rapid restoration of tissue integrity and breaking strength in healing fetal wounds is mainly a function of fetal wound collagen. In this study, the fetal and adult tissue responses to injury were characterized in terms of changes in collagen biosynthesis. Linear wounds and unwounded skin were incubated with radioactive proline, and collagen synthesis was measured as isotope incorporation into collagenase-sensitive protein. Likewise, noncollagen protein synthesis was represented by isotope incorporation into collagenase-resistant protein. Adult wounds demonstrated a preferential stimulation of collagen as compared with noncollagen protein synthesis after wounding. In contrast, both collagen and noncollagen protein synthesis were significantly elevated in the fetus during the first 5 days postwounding. Despite marked increases in fetal wound collagen synthesis above both unwounded fetal skin and adult wound levels, fetal wounds exhibited no evidence of excessive collagen deposition or scar formation after wounding. These findings suggest that the fetal response to tissue injury is a function of the distinctive qualities of fetal fibroblasts associated with the extracellular wound matrix and may involve rapid collagen turnover and degradation.


Fetoscopic surgery for the treatment of congenital anomalies. Fetoscopic techniques may broaden the indications for prenatal surgical intervention by obviating the risks of hysterotomy. For example, congenital obstructive uropathy has been treated by open vesicostomy and percutaneous catheter placement. The open approach is appropriate only for highly selected fetuses because of the inherent risks, whereas catheter drainage, though a safer procedure, is only useful for short-term therapy late in gestation due to frequent catheter obstruction and migration. The natural history of congenital obstructive uropathy mandates the need for improved therapy earlier in gestation, in order to salvage fetuses who would otherwise die of renal failure and pulmonary hypoplasia. We have developed a potential solution to this problem in which surgery is performed on the fetus without the risks of hysterotomy. Endoscopic fetal surgery uses a telescopic lens and operating instruments that are passed through small "ports" in the uterus. A bubble of CO2 is used to displace amniotic fluid and provides excellent visualization in a magnified field. This approach is considerably less invasive than open fetal surgery and, therefore, is less likely to provoke preterm labor. In this study we corrected obstructive uropathy in midgestation fetal lambs using a new, expandable wire mesh stent that is placed endoscopically and should provide more reliable bladder drainage than existing catheters. The fetoscopic surgical approach can potentially expand the indications for in utero surgery by decreasing fetal risks, facilitating intervention earlier in gestation, and reducing preterm labor. As a consequence, the potential now exists to correct non-life-threatening malformations in utero.


Postoperative apnea in infants.

Postoperative apnea in infants. This is a review of 127 neonates evaluated for postoperative apnea and bradycardia (A&B) after inguinal surgery. The patients could be divided into three groups based on postconceptional age (PCA) at operation. Ten of 29 patients operated on at PCA of 33 to 39 weeks developed episodes of A&B. Preoperative assessment was not reliable in their identification. In the second group of 54 patients at PCA 40 to 44 weeks, 8 developed A&B, whereas in the third group of 44 patients at PCA of 45 to 60 weeks 1 patient developed A&B. In the latter two groups preoperative assessment identified all patients at high risk. We conclude that after PCA of 40 weeks patients at risk for A&B can be identified preoperatively. Patients operated on up to 39 weeks PCA should all be observed in the hospital.


Operative intervention for pediatric liver injuries: avoiding delay in treatment. To identify the physiological and anatomic factors that characterize the need for operative management of blunt pediatric liver injuries, the case records of 106 pediatric trauma victims with liver injuries over a 6-year period were reviewed. Sixty-nine patients were managed without operation (nonoperative) and 37 underwent operation, 7 with penetrating and 30 with blunt liver injuries. Of these 30 patients, 21 underwent laparotomy due to blunt liver injuries (operative); the remaining 9 patients required operation due to associated intraabdominal injuries. Nine (45%) of the 21 operative patients had major hepatic vein or retrohepatic vena caval injuries, 7 of whom died. Overall mortality was 9.4% (10/106). When nonoperative and operative groups were compared, those who underwent laparotomy due to blunt liver injuries: (1) had significantly lower Champion and Pediatric Trauma Scores due to multisystem injury; (2) had 25% or greater lobar disruption with pelvic blood collections on computed tomography scan; (3) underwent early transfusion within 2 hours of admission (18/21); and (4) were frequently found to have a major hepatic vein or retrohepatic vena caval injury at the time of operation. Only one patient successfully managed without operation received greater than 30 mL/kg of blood products within 24 hours of admission. As selective nonoperative management of pediatric liver injuries gains widespread acceptance, the identification of factors that predict the need for operative intervention will limit the potential risks of delay in treatment.


Sarcomas of the flexor fossae in children: is amputation necessary? Successful management of sarcomas of the extremities in children implies not only achievement of local control but also satisfactory function and maintenance of the growth potential. The popliteal and antecubital fossae, because of their complex neurovascular anatomy, all of which is essential, make resection with satisfactory margins difficult. We reviewed our experience with 14 patients (3 to 20 years old; median, 13 years) with soft tissue sarcomas arising in the popliteal (11 patients) or antecubital (3 patients) fossae. There were four rhabdomyosarcomas (3 alveolar, 1 embryonal) and 10 other sarcomas, the most frequent being synovial sarcoma (5 patients). Chemotherapy was given to all patients with rhabdomyosarcomas. The one patient presenting with metastatic disease was treated, after biopsy of the primary, by chemotherapy and radiation and survived 21 months. In three patients, the primary management was an above-the-knee amputation and two of three survived (3 and 43 months). In 10 patients a wide local excision of the primary tumor was performed. Radiation therapy was administered to five, either as external beam (3 patients) or as brachytherapy (2 patients). In this group, there were no local recurrences. Four patients remain free of disease (4 months to 18 years) and one developed pulmonary metastasis. Among the five non-irradiated patients, three developed local recurrences, requiring above-the-knee amputation for disease. The fourth patient relapsed in the lung and only one of the five is free of disease at 36 months. Of the 8 patients not treated with amputation, one acquired a leg length discrepancy, which required correction, and one has a minimal extension deficit of the knee.(ABSTRACT TRUNCATED AT 250 WORDS)


Allopurinol prevents intestinal permeability changes after ischemia-reperfusion injury. Under normal conditions the intestinal mucosa is impermeable to potentially harmful materials from the intestinal lumen. Mucosal disruption promotes bacterial translocation, which is postulated to be a fuel source for sepsis and multiorgan failure. We have previously demonstrated that mesenteric ischemia-reperfusion (I/R) injury increases intestinal permeability (IP); however, the mechanism remains unclear. This study was designed to examine the hypothesis that changes in IP, after I/R injury, are mediated by xanthine oxidase-generated, oxygen-derived free radicals. Thirty-three Sprague-Dawley rats (weighing 300 to 400 g) were included in this study. Group 1 (n = 10) received enteral allopurinol, a xanthine oxidase inhibitor, 10 mg/kg daily for 1 week prior to mesenteric ischemia. Group 2 consisted of 11 untreated, ischemic animals. Groups 1 and 2 were subjected to superior mesenteric artery occlusion with interruption of collateral flow for 20 minutes to produce ischemic injury to the intestine. An additional 12 rats (group 3), served as nonischemic controls (sham). A loop of distal ileum was isolated and cannulated proximally and distally to allow luminal perfusion with warmed Ringer's lactate at 1 mL/min. IP was determined in all groups by quantitatively measuring the plasma-to-luminal clearance of chromium (51Cr)-labeled ethylenediaminetetraacetate (EDTA) at baseline, during ischemia and 20, 40, and 60 minutes after reperfusion. Complete ischemia produced significant increases in IP over baseline values in the untreated rats (group 2, baseline: 0.49 +/- 0.006, ischemia: 0.149 +/- 0.039) compared with sham rats (baseline: 0.41 +/- 0.006; ischemia: 0.047 +/- 0.009) or allopurinol-treated rats (baseline: 0.098 +/- 0.020, ischemia: 0.073 +/- 0.012, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)


Hypoxia-induced bacterial translocation in the puppy. Because hypoxia is one of the most common major stresses to which a neonate is exposed, we postulated that it alone might be the cause of intestinal bacterial translocation, which could be the underlying etiology of neonatal sepsis. An animal model, in which hypoxia is the sole stress, was developed in our laboratory and tested in 18 puppies to determine the effect of hypoxia and reoxygenation on intestinal bacterial translocation. In group I (n = 8), following laparotomy and cannulation of the superior mesenteric vein (SMV), the FIO2 was decreased from 21% to 9% for 90 minutes followed by reoxygenation at 21% for 120 minutes. The abdomen was closed and the animals were allowed to recover. After 24 hours the mesenteric lymph nodes (MLNs), spleen, and liver were harvested for bacterial determination and the ileum and jejunum for histological evaluation. Group II (n = 7) was treated the same as group I with the FIO2 maintained at 21%. Group III (n = 3) animals were killed, without intervention, for bacterial analysis. In group I, the systemic PO2 decreased by 75%, SMV PO2 decreased by 64%, and oxygen delivery to the small bowel decreased by 80% in comparison with group II. The mean arterial pressure and cardiac output were not significantly different between group I and group II; however, the mucosal blood flow was decreased by 60% (P less than .001) in group I. Arterial and SMV blood lactic acid levels were unchanged in group I in comparison with group II, suggesting that anaerobic metabolism was not initiated in the splanchnic circulation during hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)


Recognition of recurrent gastroesophageal reflux following antireflux surgery in the neurologically disabled child: high index of suspicion and definitive evaluation. Multiple symptoms suggestive of gastroesophageal reflux (GER) developed in 181 of 240 children (75%) with profound neurological impairment (NI) following operative management of GER. Diagnostic testing was performed in 102 children, 56% of patients with symptoms. Recurrent GER was evident on one or more diagnostic studies in 46% of children evaluated. Significant differences (P less than .05) were found in the testing protocols of children with studies positive for GER and those individuals with negative tests. Children with study-documented recurrent GER: (1) had testing conducted at a more remote time postoperatively; (2) received a greater number of total tests; (3) were evaluated by more than one type of diagnostic test; and (4) underwent upper endoscopy and pH monitoring more frequently. No single clinical symptom was predictive of study-documented recurrent GER. These results suggest that recognition of recurrent GER after an antireflux operation in a child with profound NI requires a high index of suspicion. Definitive evaluation of children with postoperative symptoms demands repeated testing over time and the use of more than one type of diagnostic test. A contrast study should be used to evaluate the mechanical properties of the fundoplication and esophagoscopy and/or esophageal pH monitoring to assess the physiological control of GER.


Quantitative and qualitative analysis of the extracellular matrix protein, laminin, in Hirschsprung's disease. Previous immunohistochemical studies have shown an abnormal distribution of extracellular matrix (ECM) proteins, including laminin, in the smooth muscle layer of muscularis externa in Hirschsprung's disease (HD) bowel. These findings supported the hypothesis that an abnormal ECM microenvironment may be responsible for the failure of migration and/or development of the neural crest cells in the gut in HD. In order to determine the cause of the abnormality in laminin distribution, solid-phase enzyme-linked immunosorbent assays and immunoblots were used to quantitate the ECM protein laminin and characterize its subunits, respectively, in extracts of the dissected smooth muscle layer of the muscularis externa. In the aganglionic bowel, laminin (median concentration, 32.4 ng/mg of tissue) was found to be present in significantly greater quantity than in both the normoganglionic bowel of the same specimen (median, 17.2 ng/mg, P less than or equal to .05) and the normal bowel of age-matched controls (median, 9.7 ng/mg, P less than or equal to .05). Laminin concentration was also found to be significantly higher in normoganglionic HD bowel (median, 17.2 ng/mg) than in age-matched control specimens (median, 10.8 ng/mg, P less than or equal to .05). No difference was observed in the subunit composition of laminin in HD and control extracts analysed by immunoblot after polyacrylamide gel electrophoresis. This study demonstrates a quantitative abnormality of laminin in the bowel in HD, supporting the hypothesis that "abnormal microenvironment" may have a role in the pathogenesis of HD.


Pulmonary growth and remodeling in infants with high-risk congenital diaphragmatic hernia. Infants born with congenital diaphragmatic hernia (CDH) have pulmonary hypoplasia, but the pattern of postnatal growth in these lungs has not been documented. The lungs of 21 children dying with CDH were analyzed to determine how the pulmonary morphology changed with age. The patients were stratified into three age groups for ANOVA analysis (less than 8 days, 8 to 21 days, greater than 21 days). Morphometric techniques previously described were used. Lung volume and weight as well as pulmonary artery length and diameter increased with age (P = .04), whereas the number of airway generations was similar for each group. Radial alveolar number also increased, particularly in the contralateral lung (P = .02). The percentage of intraacinar artery muscularization decreased with age (P = .02), while larger intraacinar arteries showed a nonmuscular structure, again particularly in the contralateral lung (P = .004). It is concluded that: (1) significant lung growth does occur postnatally at the alveolar level after CDH repair; and (2) there is postnatal vascular remodelling resulting in larger and less muscular arteries. These changes should contribute to a decrease in pulmonary arterial hypertension over time. However, the time period over which these changes occur exceeds the current limitations of invasive support measures such as extracorporeal membrane oxygenation. Elucidation of the factors responsible for this growth could result in new therapeutic strategies to enhance or accelerate postnatal pulmonary development in infants with CDH.


The challenge of transferring responsibility for diabetes management from parent to child. To emancipate from their parents, children and adolescents with diabetes eventually must assume responsibility for self-care. The challenge that parents and health care professionals face is deciding when and how to transfer this responsibility from parent to child. Inappropriate transfer of self-care responsibility can precipitate poor metabolic control and strain parent-child relationships. By planning the gradual transfer of this responsibility based on children's cognitive abilities, maturity level, demonstrated self-care skills, and family environment factors, health care providers can minimize these problems.


Relationships between parental ratings of infant temperament, risk status, and delivery method. One hundred forty parents rated the temperament of their infants between the ages of 4 and 8 months. Analyses of the data examined the relationships between temperament and infant risk status (high or low), delivery method (vaginal or cesarean section), and the combined effects of infant risk status and delivery method. Although high-risk and low-risk infants were similar on the easy-difficult profile ratings of the revised infant temperament questionnaire, high-risk infants were rated more adaptable and more positive in mood than were the low-risk infants. Low-risk infants delivered by cesarean section were rated less optimally on three of the temperament factor scores, including withdrawal, mood, and adaptability. Interpretations of these findings are discussed and suggestions are offered for nurse practitioners and their provision of pediatric care to infants and their families.


Negotiating with clinical agencies for nurse practitioner student experiences. Selecting appropriate agencies and preceptors for pediatric nurse practitioner (PNP) students is vital for an optimal clinical educational experience. Agencies that are committed to the role of the nurse practitioner are usually willing to teach students. This article explores the process of negotiating clinical placement for PNP students. Those PNPs who wish to serve as preceptors may also benefit from this information.


Implementation of "Open Airways" as an educational intervention for children with asthma in an HMO. This article describes the adaptation and implementation of an existing pediatric asthma-management educational program, Open Airways, for members of a large group practice health maintenance organization. Seventy-four children ages 4 to 14 years and their families were randomized into one of seven class cohorts as part of a larger study of pediatric asthma management. The Open Airways program was modified to increase the emphasis on behavioral change and medication information and to reflect the different sociodemographic makeup of the population, compared with that for which the program was developed. Of the 74 families, 62 attended at least one class, and 47 of these attended five or more classes. Evaluations after classes suggest an increase in parental confidence in managing their child's asthma and an earlier use of medications. Health care providers may be able to adapt similar programs for successful use with their populations.


School injuries: what we know, what we need. Schools are the site of a substantial number of unintentional injuries each year. Current knowledge regarding the study of causes and implications of school injury is summarized in a review of the research literature. A discussion of future investigations and better management of school injuries focuses on research issues, practical management, and nursing concerns. Operational definitions and reporting mechanisms are emphasized as research needs. Practical management and nursing concerns include routine reporting, student supervision, treatment of injuries, communication with parents, and legal (liability) responsibilities.


Physiologic sequelae of prematurity: the nurse practitioner's role. Part VIII. Neurologic conditions. Advances in neonatal care enable smaller and sicker babies to survive. These babies are at increased risk for long-term neurologic sequelae: intraventricular hemorrhage, hydrocephalus, and seizures. This article, the eighth in a series, deals with the follow-up of premature infants with these sequelae, including recognition of shunt infections and failure, recognition and treatment of seizures, and immunization of preterm infants with neurologic problems.


Modulation of human gingival fibroblast cell metabolism by methyl mercaptan. Methyl mercaptan (CH3SH) is a malodorous compound whose levels are elevated in mouth and crevicular air of individuals with active periodontal disease. Since it may play a role in the disease process, its effects were evaluated using human gingival fibroblast cultures and viable porcine unkeratinized oral mucosal tissue sections. Results showed that the protein content of CH3SH-exposed cell cultures pulsed with [14C]-labelled glycine and proline was decreased by approximately 25%. Furthermore, this deleterious effect was irreversible in test cultures subsequently incubated for 24 h in a control 95% air/5% CO2 mercaptan-free environment. The supporting slab-gel electrophoresis profiles yielded evidence that exposure to CH3SH caused an alteration in collagen metabolism and a pooling of Type I procollagens. In addition, DNA synthesis was suppressed in CH3SH-exposed cultures by 44.1% at the 24 to 26 h peak of DNA synthesis. This is a true inhibition and not a shift in peak of maximum DNA synthesis as the shape and location of time-course curves of control and test systems is very similar. Proline transport study using [14C]-proline indicated a reduction in proline transport in the range of 40 to 50% in cultures exposed for 24 to 30 h to CH3SH. Significantly even 15 min exposure to 6.7 ng CH3SH/ml of incubating atmosphere suppressed proline transport by approximately 24%. This indicates that even brief exposure to low concentrations of CH3SH has a significant adverse effect on proline transport. Fluorescent staining of tissue sections exposed to mercaptan indicated that the agent elevated the number of cells stained with vital dye.(ABSTRACT TRUNCATED AT 250 WORDS)


Analysis of chondroitin sulfate isomers in the periodontium of the monkey using high-performance liquid chromatography. Glycosaminoglycan (GAG) was extracted from monkey periodontium, consisting of gingiva, periodontal ligament, alveolar bone and cementum, and from dental pulp and dentin by digestion with Pronase E. Unsaturated disaccharide isomers formed by chondroitinase AC digestion from chondroitin sulfate were labeled with dansylhydrazine and analyzed by high-performance liquid chromatography. These tissues showed different molar ratios of the unsaturated chondroitin sulfate disaccharides. The ratio of delta Di-4S to delta Di-6S was lowest in the dental pulp, followed by the gingiva, periodontal ligament, dentin, alveolar bone, and cementum, in that order. It was greater in the calcified than in the uncalcified tissues.


Platelet-derived growth factor reduces the inhibitory effects of lipopolysaccharide on gingival fibroblast proliferation. Lipopolysaccharide from a variety of bacterial sources is known to inhibit gingival fibroblast proliferation and synthetic activity and has been implicated in the pathogenesis of periodontal inflammation. However, it may be involved not only in pathogenesis but also be responsible for delayed wound healing following periodontal therapy. The aim of this investigation was to determine whether the inhibitory effect of LPS on gingival fibroblast proliferation could be reversed by growth factors. Human gingival fibroblasts were cultured in the presence of varying concentrations of platelet-derived growth factor (PDGF) or Salmonella enteritidis LPS to determine the optimal concentrations for stimulation and inhibition of proliferation respectively. The effect of PDGF on LPS inhibition of fibroblast proliferation was studied by combining PDGF and LPS together at the outset of the experimental period or adding PDGF to cells which had been previously primed with LPS. Cell proliferation was monitored by incorporation of 3H-thymidine into precipitable DNA. The results indicated that maximal inhibition of fibroblast proliferation was obtained with 50 micrograms/ml LPS and maximal stimulation of proliferation with 5 ng/ml PDGF. PDGF was found to restore the proliferative activity of the cells exposed to LPS to approximately 60% of their control counterparts. A similar value was obtained for cultures exposed to PDGF after an extended priming period of LPS exposure. Subtle differences were noted in the time taken for cells to complete their cell cycle in the various culture conditions and this may reflect variations in subpopulations of cells in their response to various mitogenic stimuli. Overall the results indicate that PDGF has the capacity to significantly negate and reverse the inhibitory effects of LPS on human gingival fibroblast proliferation.


Inhibition of human endothelial cell proliferation in vitro in response to n-butyrate and propionate. The study aimed to investigate the effects of n-butyrate and propionate on the proliferation and viability of human endothelial cells in culture. Proliferation was assessed by a 24-hour bromodeoxyuridine pulse labelling and immunoperoxidase method and viability was assessed by a colorimetric viability (MTT) assay. Endothelial cells were isolated from human umbilical vein by collagenase digestion. Experiments were performed on 96-well plates and cultures were exposed to different concentrations of n-butyrate and propionate for 2 days. n-butyrate and propionate caused significant reductions in the proliferation of endothelial cells at concentrations of 1.25 mM and 10 mM respectively (p less than 0.05); the reduction in proliferation was dose-dependent for both agents. n-butyrate was a more potent inhibitor of proliferation than propionate. However, there were no significant effects on the viability of the cells with both agents up to the highest concentrations tested (25 mM). The data indicate that n-butyrate and propionate inhibit endothelial cell proliferation which may contribute to the pathogenic effects of dental plaque in periodontal disease.


Longitudinal monitoring of humoral antibody in subjects with destructive periodontal diseases. Fifty-one subjects (16-61 years old) with evidence of prior destructive periodontal disease were monitored clinically and immunologically at bi-monthly intervals for up to 5 yr. Periodontal disease activity, determined as new attachment loss, was detected in 33 of these subjects. Only 4 of 51 subjects failed to show an elevated serum antibody level to any of the 18 subgingival species tested. The antibody level threshold established for periodontally healthy subjects was exceeded most often in diseased subjects with serum antibody to Actinobacillus sp., P. gingivalis, E. corrodens, C. concisus, F. nucleatum and P. intermedia in that order. In general, most serum antibody levels to subgingival species remained relatively consistent for periods as long as 5 yr. However, major increases and decreases in antibody could be detected to at most one or two species in individual subjects. In addition, prolonged, steady increases and decreases in antibody to specific species could be detected in certain subjects. These findings suggest that major changes occurring in serum antibody may reflect fluctuations in the nature of the infection. Differences were observed in the antibody level to specific species when subjects were divided into subsets on the basis of clinical criteria. These included high levels of antibody to A. actinomycetemcomitans Y4 in LJP and RPP subjects and to A. actinomycetemcomitans 29523 in LJP and GJP subjects.


A preliminary evaluation of the use of a redox agent in the treatment of chronic periodontitis. A small-scale clinical trial was carried out to evaluate the effect of a redox agent, methylene blue, on microbiological and clinical indices of chronic periodontitis. Methylene blue was applied subgingivally on a daily basis for 7 d to 25 test sites in 7 patients and the sites evaluated clinically and microbiologically for up to 14 d: 25 control sites in the same patients received sterile water. The test sites showed statistically significant differences from the control sites in terms of changes in a number of clinical and microbiological indices. In the test sites the proportions of anaerobes, Gram-negative anaerobes, spirochetes and motile bacteria decreased, as did the crevicular fluid flow, while the proportions of facultative anaerobes and cocci increased. These changes are indicative of a shift towards periodontal health. No significant differences were observed between the test and control sites in terms of bleeding on probing or pocket depth. The encouraging results of this preliminary study suggest that the use of redox agents in the treatment of chronic periodontitis warrants further investigation.


Phospholipase A2 in rat gingival tissue. Phospholipase A2 (PLA2) is a proinflammatory enzyme in the synovial fluids of all--and sera of some--patients with rheumatoid arthritis. Due to the similarities in pathogenesis between rheumatoid arthritis and periodontitis, we sought to study the enzymatic properties of PLA2 in periodontal tissue. In this study, we demonstrated PLA2 activity in rat gingival tissue, about 80% of which was present in the cytosolic fraction. We characterized the cytosolic PLA2 enzyme with respect to substrate specificity, sensitivity to detergent, Ca2+ ion dependency and optimum pH. We found that phosphatidylethanolamine, rather than phosphatidylcholine, was the preferred substrate, the Ca2+ ion was essential for the expression of PLA2 activity, the enzyme was active over a broad pH range, with the optimum at pH 9.0, and sodium-deoxycholate inhibited the enzyme activity strongly in a concentration-dependent manner. These results are consistent with those which have been obtained with synovial fluid PLA2 and suggest that gingival PLA2 may be involved in the pathogenic processes of gingivitis and periodontitis.