Robert H. Connors

Pulmonary embolism in children

The diagnosis of pulmonary embolism (PE) is seldom considered in the pediatric patient; however, pulmonary embolic phenomenon occur with a greater frequency than is generally recognized. Reports of all autopsies performed at the University of Michigan during the 25-yr period 1955 through 1979 were reviewed. All cases of pulmonary thromboembolism in infants and children ranging in age from 0 to 19 yr were studied; patients with emboli from fat or tumors and patients with primary pulmonary artery thrombosis were excluded. The records of 116 children with PE were evaluated. The sex distribution was equal and the average age was 8.0 yr. Age itself was not an independent risk factor for the development of PE. The primary disease processes of shunted hydrocephalus (15.2%), accidental trauma (8.4%), heart disease (4.5%), infection (4.4%), neoplasia (4.0%), and general medical illness (1.8%) were identified as significant risk factors for the development of pulmonary emboli. In the group with neoplasia, children with solid tumors (6.7%) were at an increased risk over the lymphomaleukemia group (2.6%) for the development of emboli. Children who had operation exclusive of the risk factors noted above (7.2%) were at an increased risk when compared to the nonoperative medical group (1.7%). Other risk factors including immobility, central venous catheterization, pre-existing hematologic disorders, and secondary infection were frequently seen. These factors, however, were not able to be studied epidemiologically. Venous thromboses were found in 40% of those children who had pulmonary emboli at the time of autopsy. Iliofemoral venous thrombosis was infrequently seen. The PE was deemed to be clinically important in 30% of the total series. In patients with clinically significant PE, only 50% had documented signs and symptoms of embolization and an antemortem diagnosis was considered in only one-third of these symptomatic patients. The total incidence of PE did not change over the 25-yr period, nor were there any significant trends in the associated risk factors. This study supports the concept that PE occurs in children with a greater frequency than is commonly recognized. Signs and symptoms of clinically significant pulmonary emboli occur in only 50% of the patients and even when the event presents clinically, it is an underdiagnosed entity. A heightened index of suspicion for PE in children is warranted.

Congenital duodenal obstruction: A 32-year review†

Although survival in infants with congenital intestinal obstruction has improved, duodenal obstruction continues to present unique challenges. One hundred thirty-eight newborns and infants (aged 0 to 30 days) were treated for congenital duodenal obstruction. Sixty-five were boys and 73 were girls. Sixty-one (45%) were premature. Forty-six had an intrinsic defect (atresia, web, stenosis, or duplication), 64 had an extrinsic defect (annular pancreas or malrotation with congenital bands), while 28 had various combinations of these. Presenting signs included vomiting (90%, bilious in 66%), abdominal distention (25%), dehydration (24%), and weight loss (17%). Although plain film abdominal x-ray was diagnostic in 58%, upper and/or lower gastrointestinal contrast studies were obtained in 71% of infants to confirm diagnosis. Thirty-eight percent of patients had associated anomalies, including Downs syndrome (11%), cardiac defects, other atresia, other trisomy syndrome, imperforate anus, and central nervous system anomalies. Fourteen patients (10%) had 3 or more other anomalies, many of which required additional surgical therapy. The operative repair of the various defects included Ladds procedure for malrotation (31%), duodenoduodenostomy (14%), duodenojejunostomy (22%), gastrojejunostomy or gastroduodenostomy (4%), excision of the web and duodenoplasty (3%), or combination of the above (22%). Gastrostomy was placed in 61%. One hundred twenty-eight patients survived (93%). The causes of death were combinations of sepsis, pneumonia, brain hemorrhage, short bowel, and cardiac anomaly. Eight of 10 (80%) who died had other serious anomalies. Twenty patients (14%) required reoperation 5 days to 4 years postoperatively for obstructing lesions (5), wound dehiscence (3), anastomotic leak or dysfunction (6), other atresias (2), choledochal cyst (1), pyloric stenosis (1), and gastroesophageal reflux (2).(ABSTRACT TRUNCATED AT 250 WORDS)

Exposure of the anterior spine. Technique, complications, and results in 85 patients.

The anterior approach to the spine is necessary for correction of some congenital spinal deformities and other conditions, including spinal trauma, infection, and tumor. The morbidity associated with this procedure has not been extensively reviewed in the literature. Between 1981 and 1986, 85 patients (41 male and 44 female) aged 1 to 77 years underwent anterior spinal fusion by an orthopedic or general surgery team (33 pediatric patients and 52 adult patients). Thirty-four patients had scoliosis, 8 had kyphosis, 24 had spinal trauma, 9 had tumor, and 10 had infection. Fifteen patients had restrictive lung disease diagnosed by pulmonary function testing (10 children and 5 adults). The thoracoabdominal approach was used in 50 patients, thoracotomy in 22 patients, and the lumbar approach in 10 patients. Two incisions were used in three patients. Correction was accomplished by interbody fusion in 36 patients (17 with instrumentation) and strut graft in 49 patients (6 with instrumentation). Twelve strut grafts were vascularized ribs and 37 were free ribs. Eighty-two patients survived (96 percent). Seventy-four complications occurring in 50 patients all resolved prior to discharge. These included 28 pulmonary complications, 27 urinary complications, and 5 gastrointestinal complications. Three patients required prolonged mechanical ventilation. Solid fusion was seen in 78 of 85 patients, whereas pseudoarthrosis developed in 7.

CONGENITAL TRACHEAL STENOSIS WITH UNILATERAL PULMONARY AGENESIS

Cogenital tracheal stenosis with unilateral pulmonary agenesis is a rate and frequent fetal combination. In an 8-year period, 5 infants (ages 2 to 6 months) with these anomalies were treated. The presenting signs and symptoms consisted of wheezing, stridor, and tachypnea and included frank respiratory failure requiring emergency therapy in several patients. The operative repair consisted of segmental resection and anastomosis in one patient, and rib-cartilage tracheoplasty in the other four. Two infants died, one of cerebral hypoxia, and the other of aortotracheal fistula. Long-term follow-up in the three survivors is satisfactory.

Newborn duodenal atresia: An improving outlook

From 1973 through 1983, 20 newborns with congenital duodenal atresia were treated. These patients are compared with our previous series and with other published series. There were no fatalities among the 19 patients who underwent operation, an improvement from the 72 percent survival rate in our previous series. Fifty-five percent of the patients had associated congenital anomalies, which frequently complicated their management. The use of a transanastomotic jejunal feeding tube resulted in delayed oral feeding and prolonged hospitalization, and cannot be recommended.

Malignancy associated with ureterosigmoidostomy: Detection by mucosa ornithine decarboxylase

Urinary diversion into the gastrointestinal tract (ureterosigmoidostomy) is associated with stepwise malignant degeneration of colonic mucosa. Early detection of such malignancy can be difficult. Ornithine decarboxylase (ODC) is an enzyme that initiates polyamine synthesis that is elevated in malignant colonic mucosa, but its level in premalignant mucosa after ureterosigmoidostomy is unknown. Ten Wistar rats underwent urinary diversion (bladder trigone to sigmoid colon), and were maintained on a regular diet with antibiotics for 6 months, then killed. All animals developed metaplastic changes histologically at the anastomosis. Mean ODC levels of colonic mucosa at the anastomosis v normal colon 8 cm proximal were 515 +/- 177 pmole v 24.5 +/- 4.4 (P less than .01). These data show that premalignant changes in colonic mucosa after ureterosigmoidostomy can be detected by elevated colonic biopsy ODC levels. Periodic sigmoidoscopy with colon mucosa biopsy for histology and ODC levels in children with ureterosigmoidostomy is recommended.

Corticosteroid therapy in hemorrhagic and septic shock in puppies

The efficacy of corticosteroid therapy in the treatment of shock remains controversial. In order to evaluate this question, the following controlled experimental study was undertaken. There were 44 puppies (2-6 kg) used to examine the effects of methylprednisolone (30 mg/kg) in both hemorrhagic and live Escherichia coli septic shock. In order to isolate the effects of steroid treatment, no volume or antibiotic therapy was given. Arterial, venous, and pulmonary artery catheterization allowed continuous hemodynamic and metabolic monitoring. One control group received steroid treatment and was not subjected to shock. Septic shock was achieved by a rapid bolus infusion of 10(9) live E. coli organisms. Hemorrhagic shock was produced by bleeding the puppy an average of 43% of his blood volume. Four septic and four hemorrhagic shock groups received either no treatment, steroids at the time of shock, or steroids 30 min before or after shock. Cardiac outputs of less than 50% of control values and significant lactic acidosis were documented in all of the shock animals. The septic groups showed more profound alterations in these parameters and a decreased overall survival. No statistically significant differences could be found, however, in the hemodynamic, metabolic or survival figures among the different septic shock groups, or among the various hemorrhagic shock animals. The anticipated preservation of cardiac output and decrease in leakage of lysosomal acid phosphatase were not seen with any treatment schedule. The theoretical benefits of corticosteroid treatment in shock could not be documented in these two models of severe septic and hemorrhagic shock in puppies.

Pediatric TPN: Efficacy and Toxicity of a New Fat Emulsion

Fat emulsions are particularly valuable in pediatric total parenteral nutrition (TPN) because they provide an isotonic solution rich in calories. Little is known about the ideal composition of fatty acid emulsions, however, and very few formulations are commercially available. A new fat emulsion using a safflower oil base has recently been approved. We have used this new emulsion to provide a significant percentage of the nonprotein caloric requirements (24 to 42%) in 4 patients requiring TPN. These patients ranged in age from 1 to 15 years and received no enteral nutrition during the 3-week course of the study. Nutritional improvement without major toxic effects was documented in each patient.

Mucosal proliferation characteristics in ureterosigmoidostomy: Effect of calcium supplement

Ureterosigmoidostomy, frequently performed in children for urinary diversion, is a known premalignant condition. Dietary calcium supplements have been shown to normalize mucosal proliferative patterns in other human premalignant colonic conditions, which might decrease the risk of cancer. However, calcium supplementation has not been investigated in ureterosigmoidostomy. We used a rat model to study the effects of increased dietary calcium on the progression to carcinoma in ureterosigmoidostomy. Twenty-five Wister rats underwent ureterosigmoidostomy by anastomosis of bladder trigone and ureters to sigmoid, and were divided into two groups: group 1, regular diet (14); and group 2, calcium supplemented (2%) diet (11). All animals received the diet for 9 months. At death the anastomosis was weighed and examined histologically. In addition, ornithine decarboxylase (ODC), an enzyme involved in polyamine synthesis that becomes elevated in neoplastic and proliferative disorders, was determined at the anastomosis and 8 cm proximal (normal colon). All animals developed proliferative metaplastic polyposis at the anastomosis. Tumor weights were 2.6 +/- 1.1 g for group 1 and 4.8 +/- 1.2 g for group 2 (P less than .05). The ODC levels were: group 1, normal colon 78.2 +/- 15.6 and tumor 321.3 +/- 58.8 (P less than .002); and group 2, normal colon 425.8 +/- 65.4 and tumor 568.0 +/- 40.9 (P = NS). The difference between group 1 normal colon and group 2 normal colon was significant (P less than .001), as was group 1 tumor and group 2 tumor (P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of perfluorochemicals on tumor growth and chemotherapy response

Hypoxia, leading to cells in resting or slow replication phases may be a cause of chemotherapy and radiation therapy resistance in some tumors. Perfluorochemicals (PFC) may potentiate response to these therapies by increasing oxygen delivery to the tumor, forcing cells into more therapy-responsive replicating phases. To assess the effects of PFC on tumor growth and chemotherapy response, 91 ACI rats bearing 1 cc flank Morris hepatoma tumors were divided into groups: Group I, control; Group II, Adriamycin (ADR) 10 mg/kg intraperitoneally (IP); Group III, Cytoxan (CTX) 100 mg/kg IP; Group IV, PFC 20 mL/kg IV; Group V, ADR and PFC; Group VI, CTX and PFC. Animals were kept in 0.5 FiO2 for 24 hours after treatment, and mortality and tumor volumes determined 2 weeks later. Tumor DNA turnover was measured using opposing pathways assay of 14C-thymidine uptake and degradation. In a separate group, tumor tissue pO2 was measured polarographically with an oxygen microelectrode before and after injection of PFC (20 mL/kg). The survival was significantly reduced in group IV (4%) compared with group I, control (73%). Both ADR and CTX slowed the growth of the tumor, while PFC alone significantly accelerated tumor growth. The tumor response to ADR was potentiated by the addition of PFC. These results were confirmed by DNA synthesis evaluation. The mean pO2 level prior to injection was 6.6 +/- 1.96 mmHg compared with 18.92 +/- 1.00 mmHg after PFC injection (P less than or equal to .01).(ABSTRACT TRUNCATED AT 250 WORDS)