Total colonic aganglionosis and Hirschsprung’s disease: shades of the same or different?

Total colonic aganglionosis is a relatively uncommon form of Hirschsprung’s disease (HSCR) occurring in approximately 2–13% of cases. It can probably be divided into total colonic aganglionosis (TCA; defined as aganglionosis extending from the anus to at least the ileocaecal valve, but no more than 50 cm proximal to the ileocaecal valve) and total colonic and small bowel aganglionosis, which may involve a very long segment of aganglionosis. Clinically, they appear to represent a different spectrum of disease in terms of presentation and difficulties in diagnosis which may be experienced, suggesting a different pathophysiology from the more common forms of HSCR. It is not yet clear whether TCA merely represents a long form of HSCR or a different expression of the disease. There are a number of differences between TCA and other forms of HSCR, which require an explanation if its ubiquitous clinical features are to be understood. There is some evidence suggesting that instead of being purely congenital, it may represent certain different pathophysiologic mechanisms, some of which may continue to be active after birth. This study reviews all that is known about the clinical, radiological and histopathologic differences between TCA and the more frequently encountered recto-sigmoid (or short-segment) and correlates them with what is currently known about the genetic and molecular biologic background to find possible pathogenetic mechanisms.     

Rotavirus diarrhea in Jewish and Bedouin children in the Negev region of Israel: epidemiology, clinical aspects and possible role of malnutrition in severity of illness

We conducted a 1-year prospective study in the Negev region of southern Israel to determine the epidemiologic and clinical patterns of rotavirus diarrhea. A total of 605 patients were studied, 392 Bedouins and 213 Jews, 441 of whom had diarrhea (449 episodes) and 164 did not. Rotavirus was the most common organism detected in children with diarrhea (63 of 444; 14%) but was rarely found in controls (3 of 163; 2%) (P less than 0.001). In 22% (12 of 54) of the rotavirus-positive patients, at least one other organism was also detected. The rate of rotavirus detection decreased as age increased, from 18% in the first year to 8% in the third year of life. Hospitalization with rotavirus diarrhea occurred more frequently in the summer. However, during winter, when diarrhea was less prevalent in the community, the proportion of cases associated with rotavirus was higher. Compared with controls, malnourished children were more likely to be hospitalized. However, rotavirus was detected in similar proportions among well-nourished and malnourished cases with diarrhea. The most prevalent rotavirus serotype was type 1 (in 69%), followed by types 4 and 2 (18 and 13%, respectively). We estimated that during the study period, approximately 2% of all Bedouin infants vs. only 0.2% of Jewish infants were hospitalized with rotavirus disease in their first year of life. Clinical signs and symptoms and stool appearance were not useful in predicting rotavirus detection. Malnutrition seems to be an important indicator of disease severity, which may explain why the toll of rotavirus-associated morbidity and mortality is particularly high among children in developing countries.     

Giardiasis in childhood.

Giardiasis is still regularly encountered in the United States, both as endemic cases from the local community as well as in patients returning from travel abroad. Giardiasis should be suspected in any child with steatorrhea, unexplained chronic diarrhea (especially if associated with growth failure), weight loss, or abdominal pain and bloating. Duodenal aspiration or small intestinal biopsy may be necessary to make a diagnosis because Giardia lamblia are not found by stool examination in 50% of symptomatic individuals. A diagnosis of giardiasis is important because the disease is curable.     

Etiology of chronic diarrhea

With worldwide use of oral rehydration solutions, the treatment of acute diarrhea does not pose much of a problem. However, chronic diarrhea is still harmful, especially for the growth and development status of the children. Between January 1993 to December 1996, patients who suffered from chronic diarrhea for more than one month duration and admitted to Dr. Sami Ulus Children’s Hospital were evaluated for epidemiological and etiologic factors. Seventy consecutive patients were evaluated. The mean age was 40.8 months and 52% were males. Malnutrition was detected in 80% of cases. Etiologic factors included celiac disease 30%, cow milk allergy 17%, bacterial and parasitic factors 26%, cystic fibrosis 10% and postinfectious gastroenteritis 10%. Eosinophilic gastroenteritis, chronic nonspecific diarrhea, pseudo-obstruction, neurofibromatosis and inflammatory bowel disease were rarely detected. Celiac disease and cow milk allergy were implicated as the most common causes of chronic diarrhea. The vicious cycle of faulty nutrition, malnutrition and infection and postinfectious enteropathy were also significant factors in the etiology of chronic diarrhea. It may be considered that cow milk protein prick test, sweat test, immunologic tests and mucosal biopsies should be performed for the definite diagnosis of chronic diarrhea.     

Generalized BCG infection, expression of multifactorial deficiency of intramacrophage bactericidal action. Anatomo-clinical study of 11 cases

In France, because of routine vaccination, BCG infection is the rule and not the exception. It may thus incidentally reveal a latent immunodeficiency. Eleven cases (10 fatal) of generalized BCG infection observed from 1967 to 1981 at the H?pital des Enfants-Malades (Paris) are reviewed. The clinico-pathologic analysis of these 11 cases showed that the underlying immunodeficient states were of various natures. They could be grouped under 3 different headings: (1) Cellular immunodeficiency, as part of a severe combined immunodeficiency (5 cases) and Di George's syndrome (1 case); (2) Deficiency in the bactericidal activity of the macrophages, either isolated (2 cases) or associated with fatal granulomatous disease (1 case); (3) unclassified conditions, probably original, associated with chronic Salmonella infection. The heterogeneity of theses cases emphasizes the complexity and diversity of the mechanisms which lead to the elimination of the intracellular agents. Because they provide useful insight into the poorly understood mechanisms of bactericidal activity of macrophages, further investigations of infantile disseminated BCG infection are necessary.     

Diabetic microangiopathy

Microvascular complications of diabetes include retinopathy, nephropathy and neuropathy. The first signs of these complications may develop in children and adolescents, particularly if insulin treatment has been inadequate. The mechanisms by which diabetic microangiopathy develop are not known, but probably include genetic influences. Several biochemical changes may interact, one important change being increased protein glycation. Important functional changes are increased organ blood flow, increased vascular permeability, abnormal blood viscosity and abnormal platelet and endothelial function. The structural hallmark of diabetic microangiopathy is the thickening of the capillary basement membrane. These changes may lead to occlusive angiopathy and to tissue hypoxia and damage. Screening for microangiopathy should start in children and adolescents after 5-y duration of the disease and 10 y of age. The screening should include retinal examination through a dilated pupil or fundus photography, urinary albumin excretion rate, blood pressure measurement and neurological examination. Several intervention trials have shown that near normoglycaemia may reduce the risk of microangiopathy. There is a curvilinear association between the risk of development and progression of microangiopathy and mean blood glucose. Therefore, optimal insulin treatment is important in children and adolescents.     

Infant botulism: First two confirmed cases in Slovenia and literature review

In Europe, infant botulism is a rare but probably under-diagnosed disease. With the intent to spread the awareness of this potentially life-threatening disease, we present a review of the literature with the emphasis on European epidemiology and a practical approach to diagnosis. We also report the first two confirmed cases of infant botulism in Slovenia and describe our way to the final diagnosis in a clinical setting where all appropriate diagnostic tests and treatment options are not readily available. The second case is particularly interesting, presenting with profound diarrhea following initial constipation, an unlikely symptom for an infant with botulism and possibly caused by Bacteroides fragilis.     

Pathogenesis, treatment, and therapeutic trials in hemolytic uremic syndrome

Diarrhea-associated hemolytic uremic syndrome is one of the most common causes of acute renal failure in childhood. Nearly all cases are the result of an antecedent infection by Shiga toxin--producing strains of Escherichia coli, especially the O157:H7 serotype. Most cases occur after ingestion of contaminated meat; however, new food sources such as leaf lettuce, alfalfa sprouts, and goat's milk have been identified, and diarrhea-associated hemolytic uremic syndrome can occur after exposure to contaminated water in recreational swimming sites. Diarrhea-associated hemolytic uremic syndrome is a systemic disease with activation of a variety of inflammatory cytokines. Kidney injury may result from direct effects of the Shiga toxin on renal tubular epithelial cells as well as endothelial cells. Early diagnosis of diarrhea-associated hemolytic uremic syndrome may be expedited by the introduction of new techniques to rapidly detect toxin and microorganism in stool samples. Optimal therapy of diarrhea-associated hemolytic uremic syndrome includes intensive management of the renal failure and serious extrarenal complications that may occur during the course of disease. The role of antibiotics in prevention and amelioration of diarrhea-associated hemolytic uremic syndrome remains controversial. Experimental therapies that are undergoing evaluation in clinical trials include SYNSORB Pk (SYNSORB Biotech, Inc., Calgary, Alberta, Canada), a drug designed to bind Shiga toxin in the lumen of gastrointestinal tract. Immunization strategies are also being developed and tested. It is hoped that with continued progress in this field the incidence of diarrhea-associated hemolytic uremic syndrome in children will be substantially reduced in the coming years.     

Adult respiratory distress syndrome in pediatric patients. II. Management

Adult respiratory distress syndrome, a clinical syndrome of respiratory failure that follows many kinds of insults, often in patients with no previous pulmonary disease, occurs in pediatric patients. This group of disorders has a typical clinical, pathologic, and pathophysiologic course, the hallmark of which is injury to the alveolar-capillary membrane with increased permeability of the pulmonary vasculature and pulmonary edema. Resolution may occur at any stage, but most patients die and many develop chronic lung disease requiring respiratory support for weeks or months. Multiple organ system failure, secondary infection, and irreversible respiratory dysfunction are responsible for the poor outcome. The underlying mechanisms that relate injury to the development of pulmonary disease are unclear. In some cases there may be direct injury to the lung, but in others, such as septic shock, there are mediators that link the initial insult to the subsequent lung injury. The leukocyte may have a central role in this process, although this is uncertain. Therapeutic measures needed to support the patient, especially increased inspired oxygen, are additional factors in the progression of lung disease. Current therapy, as summarized in Table II, is primarily supportive. Efforts to treat ARDS after it is clinically apparent have been disappointing. The pathogenic mechanisms that lead to ARDS are probably well advanced by the time the syndrome is diagnosed on the basis of the usual clinical signs. Therefore an emphasis on understanding the mechanisms of lung injury so that specific markers can be used to predict which patients will develop ARDS, allowing intervention in the early stages of the process, may prove rewarding.     

Three cases of a rare disease, congenital chloride diarrhea, summons up the variation in the clinical course and significance of early diagnosis and adequate treatment in the prevention of intellectual disability

Congenital chloride diarrhea (CLD) (OMIM #214700) is a rare, autosomal recessive disease that is characterized by increased chloride loss in stool. As a result of electrolyte loss, surviving patients might have some complications, one of them being mental retardation. Here, we present three new Turkish patients with new mutations in the SLC26A3 gene. Although the clinical picture of the patients might be similar, consequences of the disease and complications might differ greatly among patients. Pediatricians should be aware of CLD as a potentially fatal or disabling disease if untreated. History of polyhydramnios, watery diarrhea, failure to thrive, poor growth, soiling, metabolic alkalosis and hypokalemia/hypochloremia should be an alarming set of findings for the diagnosis. Salt substitution therapy started early in life prevents early complications, allows normal growth and development, and favors good long-term prognosis.     

Reappraisal of the Peruvian and Brazilian lower titer tetravalent rhesus-human reassortant rotavirus vaccine efficacy trials: analysis by severity of diarrhea

OBJECTIVES AND METHODS: With the purpose of better understanding the efficacy of the lower titer [4 x 10(4) plaque-forming units (pfu)] tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) against diarrheal episodes of different severities, the Peruvian and Brazilian efficacy data were reanalyzed with a 20-point scoring system. Mild, moderate/severe and very severe rotavirus diarrhea were scored as 0 to 8, 9 to 14 and >14, respectively. RESULTS: In the Peruvian study one dose of vaccine yielded 64% (P = 0.04) protection against pure cases of rotavirus disease (i.e. those in which no other enteropathogen was found) with clinical scores ranging from 9 to 14. Protective efficacy against very severe rotavirus gastroenteritis could not be assessed because of the small number of cases. In Brazil there was a trend in preventing "all" and "pure" cases of rotavirus diarrhea scored 9 to 14 (44%, P = 0.06, and 45%, P = 0.08, respectively) and the vaccine was 75% (P = 0.02) protective against pure rotavirus diarrhea scored >14. No protection was observed for mild rotavirus diarrhea (scores <9). These data were compared with those from trials in Venezuela (4 x 10(5) pfu/dose), US (4 x 10(4) pfu/dose and 4 x 10(5) pfu/dose) and Finland (4 x 10(5) pfu/dose). Combining the Peruvian (one dose, pure cases) and Brazilian studies together, the levels of protection against 9- to 14-scored rotavirus diarrhea are comparable with those from the Venezuelan (47%) and American (57, 57 and 65%) efficacy trials. In Brazil the level of protection (75%) against pure, >14-scored rotavirus diarrhea is similar to the efficacy rates yielded in the three US trials (82, 80 and 69%) and the Finnish trial (100%) for episodes of the same severity. CONCLUSIONS: Our reanalysis provides evidence that, at least against moderate/severe rotavirus gastroenteritis, RRV-TV, 4 x 10(4) pfu/dose is potentially as efficacious as RRV-TV, 4 x 10(5) pfu/dose, even in settings with very high rotavirus disease burden. The reanalysis of the Peruvian data suggests that one and three vaccine doses may yield similar efficacy rates. It is also suggested that vaccine efficacy against most severe episodes in Peru and Brazil was not evident because of the trial design used in those studies (i.e. prospective, active home surveillance rather than a catchment trial), resulting in too few cases of severe disease even in the placebo group. To confirm these findings, future trials with this vaccine are necessary in developing countries with high diarrhea morbidity rates. These trials should use catchment designs and focus on the evaluation of the efficacy of one or three doses of RRV-TV against moderate to severe/very severe rotavirus diarrhea.     

Under fives mortality in the urban slums of Lucknow

The main objective of this study was to elicit proportional cause specific mortality in the underfives in the urban slums of Lucknow in North India. The families with under five mortality in the 28 randomly selected slums in 1993 were located from the records of the slum health workers and verbal autopsy was conducted to assign a cause of death. There were 71 deaths among 2796 children. The annual under five mortality was 25.4 and the under five mortality rate was 126.7. After the neonatal period, “high fever” that could not be classified into any other disease incorporated in the verbal autopsy instrument, was the most common symptom associated with death, seen in 21.1% cases (95% C.I.: 15.5–34.4%) followed by these diseases: pheumonia in 19.7%, diarrhea in 18.3% and measles in 11.4%. “High fever” as the leading symptom associated with death is being reported for the first time from the urban slums of India. There is an urgent need to identify the underlying etiologies of death due to “high fever” and the policy implications are that children with fever must receive immediate and continued medical attention till the symptom persists.     

Crohn’s disease,autoimmune thyroiditis,and beta-thalassemia trait in an adolescent: an unusual combination of diseases

An adolescent with complaints of fatigue, tachycardia, abdominal discomfort, and blood-stained diarrhea is presented. Clinical and laboratory evaluation revealed a microcytemic anemia with iron deficiency, beta thalassemia, and thyrotoxicosis with thyroid antibodies. Crohn’s disease was confirmed on endoscopy. A rapid normalization of clinical and laboratory parameters was observed following the initiation of therapy and further exacerbation of her illness was prevented. Although the simultaneous occurrence of Crohn’s disease, autoimmune thyroiditis, and a beta-thalassemia trait is likely to be coincidental, the combination of an autoimmune thyroid disease and Crohn’s disease is rare in pediatrics. Several issues of importance in the treatment of these conditions are discussed. Rectal blood loss associated with Crohn’s disease may lead to severe iron deficiency, especially in patients with preexistent beta-thalassemia trait, and those with thyroiditis are prone to developing hypothyroidism following treatment, requiring that they be monitored closely.     

Educational paper

Improvements in our understanding of the genetic basis of human disease and increased utilization of genetic testing have identified a variety of heritable disorders associated with the onset of benign or malignant neoplasms during childhood. In many cases, the optimal management of affected children is dependent upon the early detection and treatment of tumors. Surveillance strategies based on the natural history of these lesions are often complex, requiring clinical examinations and radiologic and laboratory studies that evolve over a patient’s lifetime. A general pediatrician may be the first to suspect one of these disorders in a patient, or may be faced with questions regarding genetic testing, cancer risk, and cancer screening. The pediatrician may also coordinate and interpret the results of specific surveillance studies. In this review, we present the genetic etiology, presentation, natural history, and surveillance recommendations for four disparate hereditary tumor predisposing syndromes, including Beckwith–Wiedemann syndrome/idiopathic hemihyperplasia, von Hippel–Lindau disease, Li–Fraumeni syndrome, and rhabdoid tumor/schwannomatosis. These examples are meant to offer the clinician practical recommendations as well as a framework upon which to base the understanding and management of other conditions associated with an increased risk to develop tumors in childhood.     

Secondary carbohydrate intolerance during diarrhea-clinical features,detection and management

Of 110 cases having watery diarrhea,sugar intolerance was observed in 75 subjects (68%), majority of whom (97%) were below 2 years. While nutritional status was not associated with the occurrence of sugar intolerance, children from rural areas had a higher incidence than urban children. Stools in children with sugar intolerance were watery, moderate to large in quantity, often explosive with a sour odour, had a pH of 6 or less and were positive for sugar. Lactose with galactose andlor glucose were the most common sugars on stool chromatography, occurring in 56% of the cases. All 75 cases of sugar intolerance had monosaccharides in stool chromatograms. Chromatography often was not helpful in pinpointing the offending sugar and did not correlate well with clinical responses. Among children with sugar intolerance continued on breast or cow’s milk (control diet) twothirds responded, and the remaining responded to lactose-free milk (LFM). LFM was found effective in cases with sugar intolerance. Failures to it were due to feeding of breast or cow’s milk. LFM was required for 3–4 days for controlling diarrhea. Failures to control diet had a significantly longer duration of intravenous fluid treatment and hospital stay than responders. However, as failure to respond to control diet cannot be predicted at the time of admission, use of lactose-free formula may be indicated for the routine treatment of sugar intolerance.     

Hemolytic uremic syndrome related to cryptosporidium infection in an immunocompetent child

Hemolytic‐uremic syndrome (HUS) is characterized by the clinical and laboratory manifestations of acute renal failure, thrombocytopenia and microangiopathic hemolytic anemia. In children, the majority of cases occur after an infectious diarrhea mainly associated with the serotype Escherichia coli O157:H7. We present a case of a 5‐year‐old boy with post‐diarrhea HUS due to cryptosporidium. The child remained on peritoneal dialysis for 24 days. However, he had a full recovery of his renal function and 6 months later, his overall condition was still very good. This is a particularly interesting case, not only due to the exceptionally rare cause of HUS, that is, the cryptosporidium, but also because of the serious gastroenteritis caused by the cryptosporidium in an immunocompetent child. It seems that in cases of post‐diarrhea HUS, apart from E. coli O157:H7, even the rarest causes of gastroenteritis should be investigated.     

Cerebral Mantle Thickness: A Measurement Useful in Anatomic Diagnosis of Fetal Ventriculomegaly

The ultrasonographic diagnosis of cerebral ventriculomegaly carries grave implications, in that affected fetuses may suffer abnormal postnatal development or therapeutic abortion. It is important for pathologists to corroborate the clinical diagnosis, but because diagnostic methodologies and criteria differ so radically, this can be problematic. The clinical diagnosis is made primarily by serial ultrasound examinations of the cerebral ventricles, spaces that can be altered postmortem, particularly when the brain is autolysed or deformed artifactually. We therefore sought to learn if examination of tissue, rather than spaces, can identify accurately those fetuses diagnosed with cerebral ventriculomegaly by prenatal ultrasound. The thickness of the cerebral mantle was obtained in 100 control fetuses aged 14 to 26 postmenstrual weeks. Statistical analysis revealed significant correlation of cerebral mantle thickness with crown–rump length, foot length, and head circumference. Twenty fetuses diagnosed with ventriculomegaly showed mantle thicknesses that were less than the control mean. In a few cases, mantle thickness fell between the mean and −1 SD; in several others, thickness was diminished by −1 SD to −2 SD; in one-half of cases, mantle thickness was 2 SDs or more below the expected mean. Head circumference was within 2 SDs of the control mean in most cases, and increased beyond 2 SDs in only two cases. Head circumference is an unreliable indicator of ventriculomegaly in the midgestational fetus. By contrast, cerebral mantle thickness is a simple and useful way of corroborating ultrasonographic diagnoses at autopsy and may also prove useful in clinical settings. Received February 13, 1998; accepted July 20, 1998.     

Non-infective pulmonary disease in HIV-positive children

It is estimated that over 90% of children infected with human immunodeficiency virus (HIV) live in the developing world and particularly in sub-Saharan Africa. Pulmonary disease is the most common clinical feature of acquired immunodeficiency syndrome (AIDS) in infants and children causing the most morbidity and mortality, and is the primary cause of death in 50% of cases. Children with lung disease are surviving progressively longer because of earlier diagnosis and antiretroviral treatment and, therefore, thoracic manifestations have continued to change and unexpected complications are being encountered. It has been reported that 33% of HIV-positive children have chronic changes on chest radiographs by the age of 4 years. Lymphocytic interstitial pneumonitis is common in the paediatric HIV population and is responsible for 30–40% of pulmonary disease. HIV-positive children also have a higher incidence of pulmonary malignancies, including lymphoma and pulmonary Kaposi sarcoma. Immune reconstitution inflammatory syndrome is seen after highly active antiretroviral treatment. Complications of pulmonary infections, aspiration and rarely interstitial pneumonitis are also seen. This review focuses on the imaging findings of non-infective chronic pulmonary disease.     

Timing of surgery for common pediatric surgical conditions

Depending upon various factors the surgical procedures in childhood are divided into three groups—immediate, intermediate and elective. The timing of surgery is probably the most important factor governing the outcome of surgical correction in pediatric surgery. With continuing research and clinical experience our understanding of the various conditions have improved and with that has come a change in the optimum timing of many surgical procedures. This paper highlights the best timing of surgery for some of the commoner pediatric surgical procedures and the reasons behind these so that the children may be referred to pediatric surgeons in time.