Pierre Brochu

One-hour blood-xylose test in diagnosis of cow's milk protein intolerance.

In this prospective study, 18 consecutive children suspected of cows milk protein intolerance (C.M.P.I.) on clinical grounds were investigated before and after challenge with cows milk. One-hour blood-xylose, serum-IgE, eosinophil count, serum-complement (C3) and a jejunal biopsy specimen for histology and disaccharidase activity were obtained from all patients before challenge. Serum-complement was measured again 24 h after the beginning of the challenge and the first three tests were repeated on the fifth day. A second jejunal biopsy was obtained in 9 of the first 10 children. 15 of the 18 children were considered to have C.M.P.I. The one-hour blood-xylose test emerged as a simple and valuable test in the diagnosis of C.M.P.I. A significant drop (51--81%) in the one-hour blood-xylose level was observed in all 15 patients. In all patients but one it dropped below 25 mg/dl. Mean value (+/- S.D.) for the group was 47.5 +/- 11.1 mg/dl before and 17.2 +/- 4.2 mg/dl after cows milk ingestion.

Short-term cyclosporine induces a remission of autoimmune hepatitis in children

BACKGROUND/AIMS The current immunosuppressive treatment of patients with autoimmune hepatitis consists of prednisone and azathioprine. High doses of prednisone used to obtain the remission of the disease are associated with serious adverse effects. To avoid harmful consequences of prednisone therapy, we proposed to treat patients with oral cyclosporine to obtain the remission of the inflammatory process. METHODS This is a pilot, multinational, multicenter, clinical trial involving children with autoimmune hepatitis. Thirty-two children were recruited, who according to international criteria were considered as having definite autoimmune hepatitis. Cyclosporine alone was administered for 6 months, followed by combined low doses of prednisone and azathioprine for 1 month, after which cyclosporine was discontinued. Biochemical remission of the disease was established by the follow-up of serum transaminase activity levels. Growth parameters and adverse effects of the treatment were recorded. RESULTS Two patients were withdrawn from the study: one for non-compliance and the other for liver failure which did not improve with cyclosporine. Of the 30 remaining patients, 25 normalized alanine aminotransferase activity levels by 6 months and all the patients by 1 year of treatment. Z-scores for height showed a trend towards improvement during treatment. Adverse effects of cyclosporine were mild and disappeared during weaning off the medication. CONCLUSIONS Cyclosporine induced the biochemical remission of the hepatic inflammatory/necrotic process in children with autoimmune hepatitis, with few and well-tolerated adverse effects.

Hirschsprung's Disease in a Family with Multiple Endocrine Neoplasia Type 2

SummaryGastrointestinal symptoms are known to occur in association with multiple endocrine neoplasia (MEN) type 2. Patients with the variant 2b are at special risk and show diffuse intestinal ganglioneuromatosis. Megacolon is frequently an early X-ray finding and is associated with hyperplastic gang

Malabsorption, hypocholesterolemia, and fat-filled enterocytes with increased intestinal apoprotein B

Eight infants presented with a malabsorption syndrome, normal fasting triglycerides, hypocholesterolemia (64.3 +/- 10.0 mg/dl), and deficiency of vitamins A and E. Plasma low-density lipoprotein, apolipoprotein B, and apolipoprotein A-I were decreased. After a fatty meal, plasma triglycerides did not increase and chylomicrons could not be identified. Lipoprotein composition was characterized by normal apoproteins, high phospholipids, and low cholesterol. Increased triglycerides were present in low-density lipoproteins. Immunoperoxidase localization of apolipoprotein B on fasting biopsy specimens showed increased staining of the lipid-laden intestinal epithelial cells compared to normals. On electron microscopy after a fat load, the enterocytes contained large numbers of fat particles vesiculating the endoplasmic reticulum. These particles, morphologically similar to chylomicrons, were also present as aggregates of well-individualized lipid droplets within dilated vesicles in the Golgi zone, but were not seen in the intercellular spaces and lacteals. This recessively transmitted condition differs from abetalipoproteinemia and from the homozygous form of hypobetalipoproteinemia and may be caused by a defect in the final assembly of chylomicrons or in the mechanism of their exocytosis.

Giant-cell pneumonia caused by parainfluenza virus.

IN 1959, Enders and collaborators I isolated measles virus from the lungs of patients dying of giant cell pneumonia. Since then, this virus has been firmly established as a causative agent of this disease in patients with leukemia ~ or immunodeficiency diseases? A recent pathology textbook describes measles virus as the sole agent responsible for giant cell pneumonia/ We describe two patients with a severe combined immunodeficiency syndrome in whom we found giant cell pneumonia caused by a parainfiuenza type 3 virus. CASE REPORTS

Benign liver tumors in children: A 25-year experience

The most common benign liver tumors are hemangiomas and hamartomas, both of mesenchymal origin. Mortality for patients with these tumors has traditionally been substantial despite benign histology. Between 1965 and 1989, 22 patients were treated for a benign liver tumor. This represents 42% of all primary neoplasms of the liver observed during this period. Incidental findings of liver tumors at autopsy were excluded from this series. There were 9 boys and 13 girls with a mean age at presentation of 2.3 years (range, birth to 14 years). Sixteen had hemangiomas and presented earlier in life (mean age, 4.4 months). In this subgroup, high-output cardiac failure was present in 58% of the newborns. Seven hemangiomas were resected, four were observed, three were treated with digitalis, diuretics, and steroids, and one received epsilon-aminocaproic acid. Nonhemangiomatous tumors included four hamartomas, one focal nodular hyperplasia, and one nodular transformation. All six were resected. There was one death early in the series. At a mean follow-up of 38 months, 21 of the 22 patients are cured or asymptomatic. In the past, mortality rates of close to 90% have prompted many investigators to advocate resection of every symptomatic hemangioma. With the availability of more sophisticated imaging techniques and refinements in the treatment of cardiac failure, surgery can be used more selectively. Hepatic resections, once considered heroic, can now be performed with minimal morbidity and virtually no mortality. The 96% survival in this series of benign liver tumors contrasts with high mortality rates reported in the literature and illustrates the spectacular improvements that have been made in the diagnosis and management of these once ill-reputed tumors.

Human papillomavirus (HPV) study of 691 pathological specimens from Quebec by PCR-direct sequencing approach.

Human papillomaviruses (HPV) are etiological agents of cervical cancer. In order to address clinical demand for HPV detection and sequence typing, mostly in pre‐cancerous cervical lesions, we applied our two‐tier PCR‐direct sequencing (PCR‐DS) approach based on the use of both MY09/MY11 and GP5 + /GP6 + sets of primers. We tested 691 pathological specimens, all of which were biopsies, 75% of which were diagnosed histologically as cervical intraepithelial neoplasia (CIN) grades I–III. In total, 484 samples (70%) tested HPV‐positive, yielding 531 HPV sequences from 47 HPV types, including two novel types. Four most frequently found HPV types accounted for 52.9% of all isolates: HPV6, 16, 11, and 31 (21.5%, 20.0%, 7.0%, and 4.5%, respectively). Some interesting results are the following: all currently known high‐risk HPV (14 types) and low‐risk HPV (6 types) were detected; HPV18 was not the 1st or 2nd but rather the 4th–5th most frequent high‐risk HPV type; the highest detection rate for HPV (86%) among samples suspected to be HPV‐infected was found in the youngest age group (0–10 years old), including 70% (44/63) “genital” HPV types; HPV types of undetermined cervical cancer risk represented 19% and of the total HPV isolates but were strongly increased in co‐infections (36.5% of all isolates). To our knowledge, this is the largest sequencing‐based study of HPV. The HPV types of unknown cancer risk, representing the majority of the known HPV types, 27 of the 47 types detected in this study, are not likely to play a major role in cervical cancer because their prevalence in CIN‐I, II, and III declines from 16% to 8% to 2.5%. The two‐tier PCR‐DS method provides greater sensitivity than cycle sequencing using only one pair of primers. It could be used in a simple laboratory setting for quick and reliable typing of known and novel HPV from clinical specimens with fine sequence precision. It could also be applied to anti‐cancer vaccine development. J. Med. Virol. 63:284–292, 2001.

Photooxidation of Parenteral Multivitamins Induces Hepatic Steatosis in a Neonatal Guinea Pig Model of Intravenous Nutrition

Photooxidation of multivitamin solutions results in the generation of peroxides. Because peroxides are associated with hepatic steatosis and fibrosis as well as cholestasis, we questioned whether multivitamins are implicated in hepatic complications of parenteral nutrition. Guinea pig pups were assigned to groups receiving intravenously either total parenteral nutrition, photo-protected or not, or a control solution (5% dextrose + 0.45% NaCl) supplemented with either a) multivitamins; b) photo-protected multivitamins; c) multivitamins without riboflavin; or d) peroxides (H2O2, tert-butylhydroperoxide). After 4 d, liver was sampled for histology and isoprostane-F2α levels, a marker of radical attack. Multivitamins as well as total parenteral nutrition were associated with steatosis (scored 0–4), the severity of which was reduced (p < 0.05) by photo protection. Although H2O2 is the major peroxide contaminating multivitamins, it did not induce steatosis scores different than the controls. Compared with controls, hepatic isoprostane-F2α content increased in animals infused with H2O2 (p < 0.05), but not in those infused with Multi-12 pediatric multivitamins or total parenteral nutrition. Results suggest that peroxides and/or free radicals are not mediators of the induction of steatosis observed with infusion of photo-exposed multivitamins, as there was no correspondence between histologic findings and hepatic levels of isoprostanes. It is suspected that a component of the multivitamin solution becomes hepato-toxic after photo-exposure, as indicated by the protective effect observed when withdrawing riboflavin. Photo-oxidation of multivitamins might be the common link between reports involving amino acids, lipids, and light exposure in the ethiology of hepatic complications of parenteral nutrition.

Epstein-Barr virus polymorphic B-cell lymphoma associated with leukemia and with congenital immunodeficiencies.

Polymorphic B-cell lymphoma seen in four patients with congenital immunodeficiencies and in two patients with leukemia receiving chemotherapy was associated with the Epstein-Barr virus (EBV). The tumors had characteristic histologic features: they were polymorphic consisting of a mixture of lymphoblasts and differentiated cells including plasma cells, and areas of hemorrhagic necrosis were prominent. The tumors were either polyclonal, monoclonal, or multiclonal. Patients with congenital immunodeficiencies who developed these tumors died despite radiotherapy, corticosteroids plus acyclovir, or a combination of intravenous (IV) immunoglobulins and alpha 2 interferon. Patients with leukemia recovered when immunosuppressive drugs were discontinued and leukemia has not recurred over a period of 2 and 4 years, respectively, in the two patients.

Meconium ileus and its equivalent as a risk factor for the development of cirrhosis: an autopsy study in cystic fibrosis

Although dehydrated obstructing mucus is thought to account for the obstructive pathology involving the lungs, the pancreas, the reproductive system, and the intestinal tract, its relationship with CF-associated liver disease remains largely hypothetical and little is known about possible risk factors. Complete clinical and autopsy records were available in 38 of 73 deaths occurring over a 10-year period. The liver was normal in only five cases, and they were all infants. Steatosis was the only lesion present in 9, hypoxic liver disease was documented in 8, and biliary cirrhosis in 16 (focal in 10 and multilobular in 6). There was no relationship between the presence of cirrhosis, gallbladder abnormalities, age at death, and clinical status recorded during the year precoding their demise. Mucus plugs characterized by amorphous eosinophilic material within proliferated bile ductules were present in 75% of children with focal or multilobular biliary cirrhosis as opposed to 14% in those without (p = 0.015). A history of meconium ileus or its equivalent was recorded more frequently (p = 0.038) in those with cirrhosis. Finally, biliary cirrhosis was invariably present when there was a history of meconium ileus or its equivalent and when mucus plugs were noted. These findings suggest that patients with intestinal obstruction are at greater risk for the development of cirrhosis and that strategies should be developed to increase the detergent capacity of bile and its flow in order to decrease the viscosity of mucus in the biliary tree.