Charles R. Smith

The histopathology of the hemolytic uremic syndrome associated with verocytotoxin-producing Escherichia coli infections

Verocytotoxin-producing Escherichia coli (VTEC) infection was present in three cases of hemolytic uremic syndrome (HUS), two fatal and one non-fatal, in which detailed histopathologic investigations were conducted. Two patients had a prodrome of bloody diarrhea, one of whom required a hemicolectomy for severe bleeding. The renal histopathology was characterized primarily by glomerular thrombotic microangiopathy (TMA) with greater than 95% of glomeruli showing changes of capillary wall thickening, endothelial cell swelling, and narrowing or thrombosis of the capillary lumen. Preglomerular arterioles were frequently thrombosed, and abnormalities of the medium-sized vessels, including endothelial cell damage and thrombosis, were also commonly observed. Gastrointestinal involvement was prominent in all three cases. The colon was most severely involved, with marked mucosal and submucosal edema and hemorrhage, in the absence of significant inflammation or widespread ulceration. Microvascular angiopathy was present in all cases, with changes ranging from endothelial cell damage to overt thrombosis. Similar pathology was seen throughout the small bowel, including the presence of TMA. In one patient, typical morphologic changes of pseudomembranous enterocolitis were found in the absence of infection with Clostridium difficile. The nature of vascular involvement in the kidneys and intestinal tract supports the hypothesis that HUS is mediated by systemic toxemia, and that endothelial cells are the primary target cells for the action of verocytotoxin.

Thoracic Aorta Injuries: Management and Outcome of 144 Patients

Rupture of the thoracic aorta from blunt injury is often lethal. Methods of operative repair vary, based on the surgeons preference and circumstances. The primary hypothesis of this study was that operative management choices would correlate with outcome. Data on demographics, injury mechanism, initial evaluation, diagnostic procedures, operative treatment, and outcome were obtained from chart review at the states eight trauma centers. Rates of paraplegia and survival were compared for different methods of operative repair. Of 63,507 hospitalized trauma patients, 144 patients sustained thoracic aortic injury (incidence = 0.23%). Sixty-four died (44.1%), most of whom died in the emergency department (26) or the operating room (12). Eighty-six patients had complete operative data for analysis, including cross-clamp time and methods of repair. No patient in the group with a cross-clamp time of less than 35 minutes developed paraplegia (p = 0.02). For the patients with longer cross-clamp times, 6 of 14 patients (42.9%) undergoing clamp and sew repair developed paraplegia, as compared to 2 of 37 patients (5.4%) repaired on bypass (p = 0.005). This study suggests that the rate of paraplegia after repair of thoracic aortic injury can be minimized with short cross-clamp times or the use of bypass when long cross-clamp times can be anticipated.

Congenital tracheal stenosis: A review of 22 patients from 1965 to 1987

Twenty-two infants with congenital tracheal stenosis (CTS) were treated in our hospital between 1965 and 1987. Diagnosis was confirmed by endoscopic and radiographic methods. Patients had a spectrum of tracheobronchial lesions from localized stenosis to more complex deformities involving the carina and bronchi. Other anomalies were found in all patients with the occurrence of vascular slings or rings in 11 patients (50%). Six infants treated nonoperatively died from severe CTS and other lethal anomalies. Five of 16 patients (31%) treated surgically survived. Localized CTS in four cases was treated by dilatation, tracheostomy, or tracheal resection with primary anastomosis (two survivors, 2 non-survivors). Funnel-shaped deformities and extensive tracheobroncial stenosis were treated by tracheal reconstruction using a variety of autogenous tissue and prosthetic grafts (three survivors, nine non-survivors). The overall mortality was 77%. A new intratracheal stent was used in two patients. The stent was a flexible steel spring covered with a silicone rubber sheath. In one patient, it was placed within the trachea at the time of repair and removed later with the bronchoscope. A stent was used in a second patient with intermittent airway obstruction following an esophageal tracheoplasty. In this case, the device failed to alleviate the obstruction, and the infant expired from progressive respiratory failure. Issues of importance in the management of infants with CTS are: (1) adequate evaluation of the tracheobronchial tree, (2) awareness that tracheobronchography may precipitate further respiratory decompensation, (3) assessment of vascular and other anomalies requiring surgical correction, and (4) selection of an appropriate therapeutic approach.

Immunohistochemical and electron microscopic assessment of childhood rhabdomyosarcoma. Increased frequency of diagnosis over routine histologic methods.

Histologic examination was carried out in 65 cases of childhood rhabdomyosarcoma (RMS), 53 embryonal, and 12 alveolar. Cross‐striations were seen on light microscopy in 12 (23%) embryonal and 4 (33%) alveolar tumors. The capacity of immunohistochemical staining (PAP technique) to increase diagnostic accuracy was assessed, using antibodies against myoglobin, the MM isoenzyme of creatine kinase, desmin, calcium magnesium‐dependent ATPase of sarcoplasmic reticulum and calsequestrin. Myoglobin was detected in 16 (30%) embryonal and eight (67%) alveolar RMS, higher numbers than obtained by viewing cross‐striations on light microscopy. The creatine kinase antibody was slightly better than the antibody to myoglobin and 15 of 25 (60%) embryonal RMS were positive when both specificities were used. The remaining three antibodies were less useful. Of 13 (two alveolar and 11 embryonal) RMS studied by electron microscopy, four showed cross‐striations, contained late myoblasts, and were positive for myoglobin. Three additional cases showed only late myoblasts and one of these was positive for myoglobin. Thus, 16 of 25 (64%) of the embryonal and seven of nine (78%) of the alveolar RMS showed either positive immunostaining or ultrastructural features of RMS. This study indicates that a combination of immunohistochemical staining, using antimyoglobin and anticreatine kinase (MM isoenzyme) antibodies, and electron microscopy are useful markers in the diagnosis of childhood RMS.

Clinical and molecular characteristics of pediatric gastrointestinal stromal tumors (GISTs).

To describe the clinical characteristics, molecular features, treatment, and outcome of six pediatric patients with gastrointestinal stromal tumors (GISTs).

Blunt cardiac injuries in children : A postmortem study

We reviewed the records of the Chief Coroner for all pediatric (< 16 years of age) trauma fatalities in Ontario (pediatric population of 2 million) for the period January 1, 1988 through December 31, 1990. Forty-one (14.5%) of 282 patients for which complete autopsy data were available had sustained cardiac injuries. Nineteen patients (46%) died at the scene of the accident, 15 patients (37%) died in an emergency department, and seven patients (17%) died during hospitalization. Rupture of a cardiac chamber occurred in 16 cases; it was the main cause of death in eight cases and a contributing factor in the remainder. Cardiac contusion without chamber rupture was present in 25 cases, but in none of the cases was it the cause of death. Brain injury was the cause of death in 16 (64%) of the cases of cardiac contusion. Cardiac injuries are more common among children who die from blunt trauma than previous reports have suggested. However, because these injuries are often rapidly fatal, many patients die before they reach a hospital. With improvements in emergency medical services and the resulting reduction in transit time, more patients may reach trauma centers alive. A high index of suspicion and rapid diagnosis and treatment of these injuries can save the lives of some of these patients.

Improvement in Post-traumatic Spinal Cord Blood Flow with a Combination of a Calcium Channel Blocker and a Vasopressor

We have recently shown that nimodipine, a calcium channel blocker, can increase spinal cord blood flow (SCBF) in normal rats and can improve SCBF after spinal cord trauma if the mean systemic arterial pressure (mSAP) is restored to normal levels by the vasopressor, adrenalin. The present study is a further analysis of the improvement in post-traumatic SCBF (measured with the hydrogen clearance technique) with the combination of adrenalin and nimodipine. In addition, image analysis was used to study the potential risk of this combination for exacerbating intramedullary hemorrhage in the injured spinal cord. SCBF, mSAP, and other physiologic parameters were measured preinjury, postinjury, and post-treatment. A 53.0-gram clip compression injury at the T1 spinal segment was delivered for 1 minute to three treatment groups (saline, adrenalin, and adrenalin plus nimodipine) comprised of five rats each. Injury caused a marked decline in SCBF and mSAP. Treatment with adrenalin alone or combined with nimodipine (1.5 micrograms/kg/min IV) improved mSAP to 100-125 mm Hg. However, adrenalin alone failed to improve SCBF, whereas nimodipine plus adrenalin produced a marked improvement of approximately 60% in post-traumatic SCBF. Morphometric analysis showed no significant difference between per cent area or volume of hemorrhage between the three treatment groups, although there was a trend for increased hemorrhage in the adrenalin-alone group perhaps due to the higher post-traumatic mSAP in this group. Further studies are required to find the minimal elevation in mSAP produced by a vasopressor that would still cause an improvement in post-traumatic SCBF by nimodipine, and to determine whether this combination improves function after spinal cord injury.

Image-guided percutaneous biopsy of musculoskeletal lesions in children

BackgroundPercutaneous core needle biopsy (PCNB) of musculoskeletal lesions can provide early and definitive diagnosis and guide decisions on management. The technique is less invasive than open biopsy and has a low complication rate.ObjectivesThe purpose of this study was to assess the diagnostic accuracy and safety of image-guided PCNB of musculoskeletal lesions in children.Materials and methodsRetrospective review of the medical records of patients referred for PCNB of musculoskeletal lesions was performed. Data collected included tumor type and complication rates. Lesion “hit” or “missed”, and core adequacy and ability to reach a definitive pathological diagnosis were reviewed and used to determine whether the biopsy was overall successful or unsuccessful.ResultsA total of 127 biopsies were performed in 111 patients. Of the 127 PCNB procedures, 114 “hit” the lesion and 13 “missed,” and 120 of the cores provided for analysis were deemed adequate for pathological interpretation and 7 were deemed inadequate. A definitive pathological diagnosis was possible in 97 of the 127 PCNB preocedures and not possible in 30. Overall 76% of the PCNB procedures were successful. The diagnostic success of biopsy in primary malignant tumors was significantly higher (92%) than in primary benign tumors (65%; P = 0.008). Six minor complications resulted from PCNB.ConclusionThis study showed that PCNB is accurate and safe for the diagnosis of musculoskeletal lesions in pediatric patients, and its results are comparable to those in adult studies.

Sudden Unexpected Death in Children with Heart Disease

OBJECTIVE To review a mortality database, and identify all sudden unexpected deaths in patients followed by the cardiac program. DESIGN Retrospective review of prospectively maintained database. RESULTS Over 8 years, we identified 80 sudden unexpected deaths, among which there were sufficient data in 69 (24 females). Patients died at a median age of 17.2 months (28 days-18.8 years). Forty-six patients had 2 functional ventricles and 23 had received palliation for a single-functional ventricle. Patients with a single ventricle died at a younger age (median 120 days; 28 days-17.2 years) and sooner after last assessment (median 27 days; 1-146 days) than patients in the biventricular group (median age 2 years; 43 days-18.8 years; median time since last assessment 49 days, 1 days-1 year) (P < .01; P = .01). Thrombosis was the most common cause (61%) of death in the single-ventricle group. Arrhythmia or presumed arrhythmia was the most common cause (46%) of death in the biventricular group. Fifty-one patients had undergone surgery. Six patients had primary electrophysiological disease, and 5 had cardiomyopathy. Eight deaths occurred in patients with pulmonary vascular disease. CONCLUSION Our study demonstrates that sudden unexpected death occurred at a frequency of at least 10 patients per year over an 8-year period with 55,730 patient encounters. We were able to determine a clinical cause of death in most patients. Arrhythmias (30%) and pulmonary vascular disease (13%) are important causes of sudden death. Simple aortic valve disease and hypertrophic cardiomyopathy are rare (4%) causes of sudden death in childhood. Infants and young children with surgical shunts comprise 23% of sudden unexpected deaths that occur within a month of the last evaluation. Close surveillance of these patients is warranted.

Sonographically Guided Percutaneous Liver Biopsy in Infants: A Retrospective Review

OBJECTIVE The purpose of our study was to assess the technical success and complication rate of sonographically guided percutaneous liver biopsies performed in infants under 1 year old at a tertiary pediatric center. MATERIALS AND METHODS Retrospective analysis of 65 biopsies performed in 61 infants between January 1999 and December 2003 was conducted. Data collected included patient demographics; details of the biopsy procedure including indication, needle type and size, number of passes, and samples; pathology results; and procedure-related complications. RESULTS The 61 infants studied included 37 males and 24 females with a mean age of 119 days (age range, 7-348 days; median age, 83 days) and a mean weight of 4.5 kg (1.9-8.3 kg). A total of 65 biopsies were performed in these 61 infants. General anesthesia was used in 66.1% of procedures. An 18-gauge needle was used in 47 (72.3%) procedures. Coaxial technique was used in seven procedures, and five biopsy tracts were embolized. In 63 of 65 procedures, the mean number of passes was 1.8. In two procedures, using a coaxial technique, 11 and 12 passes were made. One biopsy was considered technically unsuccessful, and 64 of 65 (98.5%) of the biopsies provided adequate tissue for pathologic analysis. There were three (4.6%) major complications related to bleeding: one requiring a blood transfusion, one requiring surgery, and one arteriobiliary fistula requiring transarterial embolization. Three (4.6%) minor complications also occurred. There were no deaths. CONCLUSION Sonographically guided percutaneous liver biopsy in infants is a good and effective diagnostic tool. The complication rate, however, even when performed by an experienced physician, is not insignificant in this age group of patients.