Biomedical subjects
Publications and source records attributed to T R Weber.
Epididymo-orchitis is an unusual cause of acute scrotal swelling in early childhood. We report the coexistence of otitis media and epididymo-orchitis owing to Hemophilus influenzae, type b in 2 children.
This report concerns 60 children with documented Staphylococcus epidermidis sepsis. There were 34 boys and 26 girls, ages 2 weeks to 15 years. The primary diagnosis included malignancy (13), congenital (13) or acquired (11) gastrointestinal disorders, prematurity (7), cardiac defect (5), hydrocephalus (2) and miscellaneous (9). Clinical presentation included fever (54), tachycardia (15), lethargy (20), hypotension (8), irritability (6), increased gastric residuals (6) and apnea/bradycardia (3). A documented source of sepsis was noted in 56 patients, including percutaneous central venous catheters (23), Broviac catheters (17), umbilical arterial catheters (6), wound (3), V-P shunt (2), cardiac defect (2), cholangitis (1), chest tube (1) and peripheral arterial line (1). There were six sepsis-related deaths, four in premature infants. Two of six infected subclavian catheters were treated successfully with vancomycin. Infection was successfully cleared in 20 of 23 infected Broviac catheters with vancomycin through the line. However, six were eventually removed for tract infection (1), persistent fever (2), and Candida sp. infection (3). Although once considered a non-pathogenic skin contaminant, S. epidermidis has emerged as a serious pathogen in hospitalized, immunosuppressed, premature and malnourished pediatric patients. Indwelling catheters enhance the likelihood of infection in these patients. Aggressive antimicrobial therapy is vital in this potentially lethal infection. Vancomycin proved efficacious in this series.
Necrotizing enterocolitis (NEC) is a serious condition affecting the neonate that may be responsive to medical management. This study evaluates the efficacy of supplemental oxygen (FiO2 40% and 50%), systemic antibiotics (ampicillin and gentamicin, cephamandole) and oral antibiotics (trimethoprim-sulfamethoxazole, neomycin and gentamicin) in a weanling rat bowel ischemia model induced by a transient (one minute) occlusion of the superior mesenteric artery. Animals were evaluated for overall survival, duration of survival, presence of bowel necrosis or perforation at seven days. Mortality in ischemic controls was 83.8%. This was reduced to 52% by FiO2 of 50%, and 40% with systemic ampicillin and gentamicin (with or without FiO2 50%) (P less than .001). Length of survival was 3.4 days in controls and increased from 5.4 to 5.9 days in rats given FiO2 50% and/or ampicillin and gentamicin (P less than .001). The incidence of bowel necrosis in controls was 60% and was reduced to 25% in rats given systemic ampicillin and gentamicin and 23.3% with 50% FiO2 and the same antibiotics (P less than .001). Systemic cephamandole and oral antibiotics had no beneficial effects.
The differentiation of mediastinal masses caused by lymphoma from those caused by histoplasmosis may require thoracotomy. We reviewed the medical records of 37 children undergoing initial evaluation for anterior or middle mediastinal masses. Sixteen had biopsy-proved lymphoma, and 21 had histoplasmosis; seven with histoplasmosis underwent thoracotomy. Age, sex, fever, weight loss, duration of illness, anemia, erythrocyte sedimentation rate, nonspecific reactants, and lung infiltrates and calcifications were similar in both groups. Masses were in the middle mediastinum in all patients with histoplasmosis and in 69% with lymphoma. Masses were in the anterior mediastinum in one of 21 (5%) with histoplasmosis and 13 of 16 (81%) with lymphoma. Among patients with lymphoma, histoplasmal complement fixation antibody titers were less than 1:8 in 14 of 15 (93%); a single patient had a titer of 1:16. The CF titers were greater than or equal to 1:32 in 14 of 21 (67%) with histoplasmosis. In children with middle mediastinal masses, a histoplasmal CF yeast or mycelial titer greater than or equal to 1:32 is strongly suggestive of acute histoplasmosis and biopsy is not required. Children not fulfilling these criteria should undergo diagnostic biopsy.
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Eight infants were treated for massive symptomatic hemangioma over a 6-year period. The hemangiomas were located in the liver in five infants and in the upper arm, lower leg, and face in one newborn each. Symptoms included congestive heart failure in six infants and platelet trapping in three newborns. Prednisone and surgical excision were curative in six of the eight patients, while two of the eight died of sepsis, congestive heart failure, and continued platelet trapping. Radiation therapy and arteriographic embolization were of limited value.
Sepsis is a major cause of mortality in patients with common bile duct obstruction. To define possible contributing factors to this phenomenon, this study evaluates the effect of biliary obstruction on the intravascular clearance and organ trapping of viable Escherichia coli using a rat model. Adult male Sprague-Dawley rats were placed in three groups: Group I controls had sham operation, Group II had division and ligation of common bile duct (CDL), and Group III underwent splenectomy. At 21 days following operation 10(9) radiolabeled E. coli were injected intravenously. At varying intervals after infusion, blood samples were obtained for clearance study. At 10 minutes, bacterial distribution in the liver, spleen, kidneys, and lungs was determined (expressed as the mean percentage of injected viable E. coli). Intravascular clearance was similar in all groups. There was a significant decrease in the trapping of bacteria by the liver of CDL rats 14.5% +/- 4.95 (vs. control = 70.0% +/- 13.3) (p less than 0.005). A significant increase of bacterial trapping by the lung was observed in the CDL animals: 63.1% +/- 7.06 (vs. controls 1.4% +/- 0.82) (p less than 0.005). There was no significant change in bacterial localization in splenectomized rats. These data suggest that biliary obstruction decreases hepatic phagocytosis and increases pulmonary localization of viable E. coli. As the Kupffer cells of the liver are usually effective in removal of blood borne bacteria, this phagocytic dysfunction may contribute to the increased susceptibility to infection noted in instances of biliary obstruction.
Forty-two infants and children with retroperitoneal solid tumors underwent second operative procedures. Twenty-three children had stage III (4) or stage IV (19) neuroblastoma and 19 had Wilms' tumor. This report suggests that second-look procedures are quite beneficial in selected cases. In children with Wilms' tumor, second procedures are most useful in those patients inadequately staged with flank operations, in cases of bilateral tumors, and in children with initially unresectable tumors following cytoreduction. Patients with significant tumor spill at a previous procedure may also benefit from early reoperation. Late recurrence of tumor, especially in children with unfavorable histology and/or hematogenous liver metastases, carries an ominous prognosis. Ten of the 19 patients with Wilms' tumor are long-term survivors (52.6%). Patients with initially unresectable (stage III) neuroblastoma occurring in the pelvis respond well to second-look resection. Children with primary tumors surrounding the celiac axis eventually died despite subsequent resection. Although the efficacy of primary tumor resection in cases of metastatic neuroblastoma remains controversial, stage IV patients with tumor resection had a longer duration of survival. Our only long-term survivors had their primary tumors resected. Second-look or delayed abdominal operations in metastatic cases may be useful in assessing the effectiveness of treatment and for sampling of retroperitoneal lymph nodes as a prognostic indicator.
Although the diagnosis of bowel perforation is frequently straightforward, it may be difficult in the neonate. Clinical signs may be limited to abdominal distension. If the patient is on assisted ventilation, pneumoperitoneum may be due to air tracking down from the chest rather than perforation. The authors report 6 cases of bowel perforation in infants in whom the diagnosis could not readily be made from the clinical findings and plain radiographs but was apparent when oral metrizamide was employed. This suggests that metrizamide can be a valuable adjunct in some cases of neonatal bowel perforation.
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Acute peptic ulcers occurred in 39 infants and children, 22 girls and 17 boys. Eleven patients were less than one year of age. Peptic ulcers were secondary to systemic disease or ulcerogenic medications in 34 cases. Hemorrhage occurred in 27 patients, perforation in 12. Endoscopy was the most useful diagnostic procedure for hemorrhage. Free air was seen on abdominal roentgenogram in all perforated patients. Ligation of the ulcer bed, vagotomy, and pyloroplasty were performed in 25 patients with bleeding. One patient required total gastrectomy. Simple plication was performed in nine patients with perforation. Plication was combined with pyloroplasty and tube duodenostomy in one patient each, and vagotomy and antrectomy were required in one patient. Operative mortality was 5.2%. There were two late deaths (Reye's syndrome and burn sepsis). No ulcer has recurred.
Broviac central venous catheters were utilized in 101 infants and children for total parenteral nutrition, administration of chemotherapy and antibiotics, and venous blood sampling over a 30 month period. A low sepsis rate (6 percent) despite the immunosuppressed condition of many of the patients and the demonstrated versatility of each catheter attests to its wide and safe applicability in this age group. Three infected catheters were sterilized by infusion of specific antibiotics through the catheter, a technique which may prove particularly valuable in patients with limited venous access.
Although protein-energy malnutrition is common in the cancer patient, the efficacy of aggressive nutritional therapy is unclear. This study evaluates the effects of protein deficiency on tumor growth, response, and chemotherapy complications in primary and metastatic rat hepatoma. Seventy-two ACI rats (200-250 g) with implanted Morris hepatoma were divided into four groups (N = 18 for each group): 1, regular diet; 2, regular diet plus cyclophosphamide (CPM) (100 mg/kg/ip); 3, protein-free diet; and 4, protein-free diet + CPM. Forty additional rats in similar groups (5-8, ten in each group) underwent intravenous injection of 6 X 10(3) tumor cells to produce pulmonary metastases. Animals were assessed for survival, tumor size, serum albumin, number of pulmonary metastases, and hemorrhagic cystitis at 2 weeks. Survival was 50% in groups 4 and 8, and 100% in the others. Serum albumin was significantly lower in rats on protein free diets (2.59 +/- 0.37 vs 3.35 +/- 0.40 g%, P less than 0.01). Tumor volume was significantly reduced by CPM (26.0 +/- 4.2 cm3 vs 1.2 +/- 0.4 cm3, P less than 0.01). Protein-free diets resulted in lower total body weight, and reduced tumor volume without, but not with CPM (14 +/- 1.6 cm3 P less than 0.05, 1.1 +/- 0.3 cm3, P less than 0.05 vs above controls). CPM reduced the number of pulmonary metastases in regular diet groups (307.2 +/- 108.3 vs 36 +/- 11, P less than 0.01), while protein free diets did not significantly affect metastases, without or with CPM (251.7 +/- 71.4 and 22.3 +/- 12.4, P greater than 0.05 vs controls). Hemorrhagic cystitis was much more common in protein free groups compared to rats on regular diets (55 vs 11%, P less than 0.01). These data indicate that protein deficiency did not affect response to chemotherapy in a primary or metastatic rat hepatoma model. However, protein deficiency results in a significantly increased rate of mortality, weight loss, and hemorrhagic cystitis which may lead to delay or cessation of cancer therapy.
Recent data suggest that the free-radical anion superoxide (O-2), an unstable, cytotoxic form of oxygen, is implicated in the pathogenesis of ischemic bowel injury. This study evaluates the role of superoxide dismutase (SOD), an enzyme specific for enzymatic conversion of O-2 in protecting the bowel from an ischemic insult. At laparotomy, the superior mesenteric artery was occluded for 1 min in 90-g weanling rats (n = 144). Animals were divided into four groups: I, untreated controls (n = 41); II, received aminophylline (AMN) 40 mg/kg ip, a substrate for (O-2) generation (n = 21); III, received superoxide dismutase (SOD) 2.5 mg/kg iv (n = 20); IV, received both AMN and SOD (n = 22). Rats were evaluated for bowel infarction, perforation, and mortality over a 7-day observation period. In 40 additional rats (10 per group) bowel ultrastructure was evaluated by scanning electron microscopy (EM) during occlusive ischemia and at various time intervals following reperfusion. Mortality was 63.4% in controls (26/41) with necrosis noted in 19 and perforation in 7. AMN resulted in a 90% mortality (19/21) (chi 2, P less than 0.05 vs control), with necrosis in 15 and perforation in 4. SOD reduced mortality to 25% (5/20) with necrosis in 4 and perforation in 1 (chi 2, P less than 0.02 vs controls) and, when added to AMN, 45.5% (10/22) (chi 2, P less than 0.01 vs AMN alone). On EM, tissue damage was minimal during occlusive ischemia, worsened by duration of reperfusion, enhanced by AMN, and reduced by SOD. These data suggest that following hypoxia, the injured bowel may be unable to appropriately handle reoxygenation. Tissue damage was related to duration of reperfusion and was worse following AMN, a xanthine derivative that might generate (O-2), a cytotoxic free radical. SOD detoxifies O2-, increases survival, and protects the bowel during reperfusion.
Three neonates with lung abscess unresponsive to antibiotic therapy underwent successful resection of infected lobes with the aid of one-lung anesthesia. This was accomplished by selective endobronchial intubation of the opposite lung and obstruction of the ipsilateral main bronchus with a Fogarty balloon-tipped catheter. This valuable technique provides protection against tracheobronchial spillage of purulent material and results in the rapid recovery of these seriously ill neonates.
This study evaluates the effects of Indomethacin (IND), Prostaglandin E1 (PGE1), and Ibuprofen (IBP) in a bowel ischemia model. Laparotomy was performed in 80-gram rats (n = 260). Transient ischemia was induced by a one minute occlusion of the superior mesenteric artery. Animals were placed in five experimental groups: (I) ischemic controls (n = 80), (II) PGE1, 80 micrograms/kg IV (n = 20), (III) IBP, 12.5 mg/kg IV (n = 60), (IV) IND 15 mg/kg IV (n = 80) and (V) PGE1 + IND (n = 20). All medications were given just prior to laparotomy. Animals were evaluated for survival, length of survival and the presence of bowel necrosis and/or perforation at seven days. Survival was 18% in controls and was reduced to 5% by IND (p less than .005). Improved survival was observed with PGE1 (35%), TBP (31%) and PGE1 + IND (35%). IND resulted in early death, while PGE1, IBP, and PGE1 + IND all increased the length of survival (p less than .05). IND-treated rats had a high incidence of bowel perforation (greater than 40%). PGE1 reversed this effect when given concomitantly with IND. IBP had a significantly lower incidence of intestinal necrosis. These data suggest that infants treated with IND who are at risk for NEC should be carefully monitored for evidence of bowel necrosis. PGE1 and IBP may have a cytoprotective role in subjects at risk for bowel ischemia.
Recent data indicates that the free-radical anion superoxide (O2-), an unstable cytotoxic form of oxygen, is implicated in the pathogenesis of ischemic bowel following reperfusion after low flow states. This report evaluates the effect of free radical scavengers on survival in an animal model with bowel ischemia. At laparotomy, the superior mesenteric artery (SMA) of 79 weanling rats (90 g) was occluded for one minute and released. Animals were divided into three experimental groups: group I acted as controls (n = 41), group II, received thiopental 5 mg/kg IV (n = 19), group III, received methohexital 2.5 mg/kg IV (n = 19). At one week animals were evaluated for mortality, mean survival time, evidence of bowel necrosis or perforation, and bowel appearance on scanning electron microscopy (EM). Mortality was 63.5% (26/41) in group I, 19 had necrotic bowel and 7 had gross perforation; 31.6% in group II (6/19) (p less than .05 versus control), with one necrotic bowel and 5 perforations; and 57.9% in group III (11/19) where 7 had necrotic bowel and 4 had perforations (p NS v control). Survival time (mean +/- SD in days) post SMA occlusion was 3.2 +/- 1.9 for group I; 4.0 +/- 1.7 for group II; and 2.5 +/- 2.0 for group III. EM showed mucosal destruction worsened by the duration of reperfusion, decreased by thiopental but not by methohexital. Thiopental, a free radical anion scavenger was cytoprotective in this animal model, as it decreased mortality and the incidence of bowel necrosis and perforation. These data support the thesis that following low flow states bowel ischemia may be related to a reperfusion injury due to the release of toxic free radical anions.
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