Elemental versus polymeric enteral nutrition in paediatric Crohn's disease: a multicentre randomized controlled trial

AIM: To compare the efficacy and safety of an elemental and a polymeric diet as the primary therapy for active Crohn's disease in children. METHODS: In a randomized, non-blind, multicentre, controlled trial in Sweden, 16 children with Crohn's disease received Elemental 028 Extra (E028E) and 17 Nutrison Standard (NuS). Remission rates (Paediatric Crohn's Disease Activity Index (PCDAI) < 10 or a PCDAI decrease of 40% or 15 points of initial level) were compared at 6 wk. RESULTS: There was no significant difference between the two groups in remission rate at 6 wk (intent-to-treat analysis): E028E 11/16 (69%) and NuS 14/17 (82%) (p = 0.438). There was no difference in the decrease in PCDAI and CDAI between patients treated with E028E and those treated with NuS from 0 to 6 wk. Patients treated with NuS gained significantly more weight than patients treated with E028E (+2.5 kg; 95% CI 0.9, 4.1; p = 0.004), this difference remained when adjusting for maximum caloric intake per kilogram bodyweight (+2.9 kg; 95% CI 1.4, 4.5; p = 0.001). Concomitant disease, complications and side effects were seen in 5/33 patients (pyelonephritis, pneumonia, intraabdominal abscess, perianal abscess and borborygmi). CONCLUSION: E028E and NuS did not differ in terms of remission rate. Patients treated with NuS gained more weight than patients with E028E. Polymeric diet may be superior to elemental diet in the treatment of paediatric Crohn's disease where the primary aim is to increase the patient's weight.     

Experience of percutaneous endoscopic gastrostomy in children with Crohn's disease

Accepted 4 November 1996
Enteral nutrition is an important mode of treatment for Crohn''s disease in children. Percutaneous endoscopic gastrostomy has been little used, even though it can facilitate the administration of an unpalatable elemental diet to an anorexic, undernourished patient. Its use is reported in 10 children with Crohn''s disease. The gastrostomy was found to be more acceptable than a nasogastric tube and was associated with only minor complications. As a consequence of improved delivery of enteral nutrition, in the year after the insertion of the gastrostomy there was a reduction in prednisolone dosage in all patients, with six patients being able to stop prednisolone completely. The SD score for height also improved significantly. It is suggested that percutaneous endoscopic gastrostomy is both useful and safe in the management of Crohn''s disease in children, particularly when compliance with an elemental diet is likely to be poor.

     

Comparative reliability of D-xylose absorption and serum beta-carotene measurements in small intestinal disease

Comparative reliability of D-xylose absorption and serum beta-carotene measurements was studied in 63 healthy and sick children suspected of having proximal small intestinal disease. Group 1 included children with newly diagnosed celiac disease (CD) who were on a normal diet (xylose, n = 46; carotene, n = 43); group 2 included children with CD in remission (xylose, n = 17; carotene, n = 15); group 3 included children with CD in remission, but who were exposed to a gluten-containing diet for an average of 1.4 years (xylose, n = 19; carotene, n = 17); and group 4 included 17 healthy children, insofar as this study is concerned, in whom serum carotene was examined. The means of serum xylose of groups 1 and 3 were significantly lower than the mean of group 2 (p less than 0.001 in both cases). D-Xylose had a sensitivity of 76.9% and a specificity of 100%. The mean serum carotene concentration for group 2 patients with CD in remission was equal to the mean of group 4, which included healthy children. The means of groups 1 and 3 were significantly lower than the means of groups 2 and 4 (p less than 0.001 in all cases). Serum beta-carotene had a sensitivity of 95% and a specificity of 87.5%. The use of these two serum tests in combination would give a specificity of 100% and a sensitivity of 94.1%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Immunosuppressive therapy of HBsAg-positive chronic active hepatitis in childhood: a multicentric retrospective study on 139 patients

We analyzed retrospectively the effect of immunosuppressive therapy in 139 children with HBsAG-positive chronic active hepatitis (CAH) observed in four liver units in Italy from 1974 to 1982. All children had been observed for at least 12 months. Of these 139 patients, 38 were treated with steroids (prednisolone or prednisone from 1 to 2 mg/kg daily), 78 with combination therapy (prednisolone or prednisone 1 mg/kg daily in combination with azathioprine, 2 mg/kg daily) and 23 were not treated. The outcome of the disease was assessed by evaluating clinical, biochemical, and histological parameters on the basis of preselected criteria. Untreated patients deteriorated more frequently than those treated with steroids (34.8% versus 13.2%, p less than 0.05) or those receiving combination therapy (34.8% versus 10.3%, p less than 0.01). Remission or improvement was observed more frequently in steroid-treated and combination-treated patients than in the untreated ones (p less than 0.001 and p less than 0.01, respectively). At the end of the study, only one untreated patient had died of liver failure. Remission was observed in about 10% of patients in the two groups of treatment, but in the untreated one, this event never occurred. Although this study is retrospective and presents some shortcomings, the data clearly indicate that steroid and combination therapy are not deleterious, and are possibly helpful, to children with HBsAg-positive CAH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy and safety of oral alendronate treatment in children and adolescents with osteoporosis

OBJECTIVES: To evaluate the efficacy and safety of oral alendronate on bone mineral density (BMD) in children and adolescents with osteoporosis. METHODS: Oral alendronate was given to 22 patients with an average age of 13.3 +/- 3.9 years (range 4.3-19 years) and BMD z-score < or = -2. Thirteen of them were treated with steroids. Dual-energy X-ray absorptiometry (DEXA) was used to measure lumbar vertebral BMD before and 14 +/- 7.75 months after treatment. Auxological, biochemical (Ca, P, alkaline phosphatase [ALP]) and densitometric parameters before and after treatment were compared for all patients. Responses of the patients taking steroids were compared with those who did not. RESULTS: Post-treatment z-scores of patients were significantly higher than basal values (p < 0.001). Average annual BMD increase with treatment was 32.74 +/- 52.57% (5.17 to 255.42%). Z-score and annual BMD increase in patients taking no steroids were significantly higher than the others (p = 0.020 and p = 0.006, respectively). Post-treatment serum ALP levels were significantly lower than their pretreatment levels (p = 0.007). After 1 year of treatment, osteoporosis completely recovered in six patients (28.6%), improved to osteopenia levels in seven patients (33.3%), continued although the z-score was increased in six patients (28.6%), and worsened in two patients (9.5%). There was no significant difference between the height standard deviation scores (SDS) of patients before and after treatment (p = 0.022). No side effect was observed due to alendronate treatment during the study. CONCLUSION: It is concluded that oral alendronate increases BMD without any side effects in osteoporotic children and adolescents, and it is cheaper and is easier to use than i.v. bisphosphonates.     

Allogeneic bone marrow transplantation versus chemotherapy in children with acute leukemia in Sweden

All children in Sweden who underwent bone marrow transplantation (BMT) with an HLA-identical sibling during a 5-year period were compared to those who were treated with chemotherapy and survived at least 3 months after remission. All patients were observed for more than 2 years after diagnosis or relapse. All 11 children with acute myeloid leukemia in first remission who underwent BMT survived compared to only 1 of 15 treated with chemotherapy (p less than 0.001). In children with acute lymphoblastic leukemia (ALL), those relapsing while on chemotherapy and treated with BMT in second to fourth remission (n = 16) had a 5-year survival of 43% compared to 16% for those treated with chemotherapy (n = 53, p less than 0.05). In children with ALL relapsing after cessation of therapy, 4-year survival was 33% for BMT (n = 6) and 55% for chemotherapy (n = 15), p = 0.05).     

Pulse steroids as induction therapy for children with ulcerative colitis

Background: Corticosteroids therapy, classically the first‐line treatment for ulcerative colitis (UC), often causes serious side‐effects. Theoretically, pulse steroid therapy where high doses are given for a shorter period may have maximal beneficial effects and minimal side‐effects as induction therapy for UC. We have therefore retrospectively compared induction therapy using pulse steroids with conventional steroid treatment for children and adolescents with moderate‐to‐severe UC. Methods: We utilized conventional steroid treatment (prednisolone 1–1.5 mg/kg/day) as an induction treatment in 17 UC patients between 1985 and 2006. Alternatively we used a 3‐day megadose pulse steroid therapy (methylprednisolone intravenously 20–30 mg/kg/day, max. 1000mg/day) in 20 UC patients from 1993 to 2006. Results: Pulse steroid therapy successfully induced rapid remission in UC patients with moderate‐to‐severe disease compared with conventional treatment (13.2 days vs 25.1 days; P < 0.05). The amelioration of Pediatric Ulcerative Colitis Activity Index score between before and 1 week after pulse steroid therapy was significantly more than that of conventional treatment (P < 0.01). No serious adverse effects were observed in the patients treated with pulse steroid therapy. However, the rate of the relapse episodes during the next 12 months after pulse steroid therapy was not significantly different from that after conventional treatment. Conclusion: These findings suggest that pulse steroid therapy is an option to be considered in children with moderate‐to‐severe UC.     

Plasma enteroglucagon in the control of childhood celiac disease

To study whether or not plasma enteroglucagon reflects changes of the small intestinal mucosa during different phases of celiac disease, we studied fasting and postprandial concentrations of plasma enteroglucagon, as well as small intestinal mucosa morphology, in children with celiac disease and in a reference group of children without gastrointestinal disorders. The children with celiac disease were studied before dietary treatment, during gluten-free diet, and during gluten challenge. In untreated celiac children we found high mean basal and postprandial plasma enteroglucagon concentrations compared with the reference group (p less than 0.001). After a gluten-free diet period of 0.2-4.5 years (mean, 1.0 year), when the small intestinal histology was normal or only mildly abnormal, there was a decrease of both mean basal plasma enteroglucagon concentration (from 81 to 17 pmol/L; p less than 0.001) and mean postprandial plasma enteroglucagon concentration (from 129 to 39 pmol/L; p less than 0.001). During a subsequent gluten challenge, which resulted in a mucosal relapse, there was a rise in mean postprandial plasma enteroglucagon concentration (from 39 to 74 pmol/L; p less than 0.005), although there was a substantial overlap in values from treated and challenged patients. These findings suggest that plasma enteroglucagon levels, particularly after a mixed meal, are correlated with the small intestinal mucosal morphology in childhood celiac disease. Determination of plasma enteroglucagon may facilitate the control of the dietary adherence during gluten-free diet and may in some children indicate mucosal relapse during gluten challenge. Thus, the number of control biopsies may be reduced.     

Placebo Controlled Trial of Systemic Corticosteroids in Acute Childhood Asthma

ABSTRACT. In a randomised controlled trial 38 asthmatic children aged 2-11 yr who had not received regular oral or inhaled steroids during the previous year, were treated with a standard regime of nebulised salbutamol and intravenous aminophylline plus either hydrocortisone and oral prednisolone for 5 days, or placebo. The children were observed throughout their hospital stay and for 3 months afterwards. There was a greater fall in heart rates in the steroid treated group on the second day of treatment (mean diff. 16 beats/min) and at discharge (mean diff. 13 beats/min); p < 0.025. Peak Expiratory Flow Rates recorded in 26 children, 13 in each group, showed more improvement on day 2 in those given steroids (mean diff 16% predicted); p < 0.05. This difference was not apparent at discharge but 9 children treated with steroids were clinically wheeze-free when they left hospital compared with 3 in the placebo group, p < 0.05. There were no differences in respiratory rate, pulsus paradoxus and arterial oxygen saturation. Trends in duration of hospital stay and relapse rate during the succeeding 3 months favoured active treatment. These findings support the use of systemic corticosteroids in addition to high dose bronchodilators to treat 'non steroid dependent' children hospitalised with acute severe asthma.     

Immunoregulation with levamisole in children with frequently relapsing steroid responsive nephrotic syndrome

The immunological and clinical effects of levamisole were studied in 10 children with frequently relapsing steroid responsive nephrotic syndrome (SRNS). The efficacy of the drug was tested during remission of the disease with all patients on alternate day steroid therapy. The lymphocyte proliferative response to phytohemagglutinin (PHA), concanavalin-A (Con-A) and pokeweed mitogen (PWM) were normal. The Con-A induced suppressor T-lymphocyte activity of 7 patients was low before treatment with levamisole 8 +/- 3.7% and increased to normal values during therapy 34 +/- 6%; p less than 0.001 (control 32 +/- 5%). In these 7 children prednisolone dosage could be decreased significantly or discontinued altogether (44.1 +/- 5.3%). Patients without immunoregulatory abnormalities did not respond to levamisole. In 3 out of 4 children tested the percentage of OKT8+ cells rose during levamisole therapy from 19.7 +/- 2.1 to 37 +/- 2.3 (p less than 0.001), thus correcting the elevated pre-treatment OKT4+/OKT8+ ratio from 3.1 +/- 0.2 to 1.5 +/- 0.2; p less than 0.001 (control 1.47 +/- 0.2). These data support the hypothesis that abnormal immunoregulation may play a role in the pathogenesis of SRNS. Treatment with levamisole can be useful in some patients with the frequently relapsing form of the disease.     

Tumor size and extent of disease at diagnosis predict the response to initial therapy for papillary thyroid carcinoma in children and adolescents

Treatment of papillary thyroid carcinoma (PTC) in children and adolescents is controversial. We previously showed that large tumor size, multifocal disease, and extensive disease at diagnosis predict recurrence. We examined 47 patients with PTC to determine whether these features predict response to treatment. Overall, 70% of the patients (33/47) remitted with initial treatment. 79% (15/19), of Class I, 86% (12/14) of Class II, and 100% (6/6) of Class III, but none of Class IV patients (n = 8) (p < 0.001) achieved remission. Tumor size for patients who entered remission (2.0 +/- 0.2 cm) was less than for patients with persistent disease (4.2 +/- 0.4) (p < 0.0005). Extent of disease at diagnosis correlated with the number of radioactive iodine (RAI) treatments (p = 0.022) and dose (p = 0.002) required to achieve first remission. We conclude that extensive disease at diagnosis and larger tumor size predict failure to remit after initial treatment of PTC in children and adolescents.     

Autoimmune hemolytic anemia

Objective  To study the clinico-hematological profile and treatment outcome in children suffering from auto immune hemolytic anemia (AIHA). Methods  Twelve children were diagnosed with auto immune hemolytic anemia over a period of four years. Direct antiglobulin test was positive in all the cases. Other causes of hemolytic anemia like thalassemia syndromes, hereditary spherocytosis, G6PD deficiency were excluded by appropriate tests. The children were followed up for 6 months to 4 years. Results  The age ranged from 7 mth to 9 yr with a mean age of 4.51 yr. All patients had pallor as the presenting complaint followed by splenomegaly (83.3%), jaundice (66.7%), fever (50%) and bleeding manifestations (16.7%). 9 patients had primary disease and 3 had secondary disease. Tubercular infection was seen in 2 patients with secondary disease. Jaundice was seen equally in both the groups. Oral prednisolone produced remission in 83.3% cases. 4 patients (3 in primary and one in secondary group) had relapse after initial response. All responded to a second course of steroids but had subsequent relapses and developed a chronic course. Conclusion  Autoimmune hemolytic anemia is an uncommon cause of hemolytic anemia in children. Tubercular infection is an underlying pathology in cases of secondary autoimmune hemolytic anemia. Although oral steroids induce remission in most of the cases, relapses are common.     

Remission induced by an elemental diet in small bowel Crohn's disease.

Seventeen children with active Crohn''s disease of the small intestine were entered into a randomised control trial comparing the efficacy of an elemental diet with that of a high dose steroid regimen. Eight children received an elemental diet (Flexical) through a nasogastric tube for six weeks, followed by reintroduction of food over six weeks during which the Flexical was stopped. Seven children were given intramuscular adrenocorticotrophic hormone followed by oral prednisolone with sulphasalazine. Two children were withdrawn from the trial. The elemental diet was equally effective in inducing an improvement in Lloyd-Still disease activity index, erythrocyte sedimentation rate, C reactive protein and albumin concentrations, and body weight as the high dose steroid regimen. Linear growth, assessed from height velocity over six months, was significantly greater in the children receiving an elemental diet.     

Efficacy of nebulized budesonide compared to oral prednisolone in acute bronchial asthma

To evaluate the efficacy of nebulized budesonide compared to oral prednisolone early in the emergency room management of acute asthma, we conducted a double-blind, placebo-controlled trial. Eighty children, 2 years to 12 years of age, with acute moderate attacks of asthma, were randomized into two groups. One group received nebulized salbutamol (0.15 mg/kg) and placebo at half-hourly intervals for three doses, and a single dose of oral prednisolone (2 mg/kg) (prednisolone group) and other group received three doses of nebulized salbutamol and budesonide (800 microg) at half-hourly intervals and a single dose of placebo tablets (budesonide group). The baseline characteristics of the two groups were similar, but after three doses of nebulization oxygen saturation, respiratory rate, pulmonary index and respiratory distress score were significantly improved in the budesonide group compared to prednisolone group (p < 0.01). The proportion of patients who were fit for discharge at the end of 2 h after the third dose of nebulization was significantly higher in the budesonide group than in the prednisolone group (22/ 41, 54% vs 7/39, 18%, p < 0.001). The data suggest that a combination of nebulized salbutamol and budesonide should be preferred in the emergency room management of children with acute moderate to severe exacerbation of asthma and who are not on prior oral or inhaled steroid therapy.     

Do inhaled steroids differ from cromones in terms of hospital admission rates for asthma in children?

AIM: The aim of the present study was to investigate the characteristics of hospital admissions in two child populations receiving different types of drugs as their regular medication for steady-state asthma. METHODS: Annual data on children aged under 16 y treated for asthma, including consumption of regular medication for asthma, numbers of hospital periods, lengths of hospitalizations and annual proportions of readmissions, were collected using patient-specific medical records from 1995 to 1999. In the Kuopio province, on average, 35.6-36.7/1000 children were on maintenance for asthma, of which 23% were receiving cromones, 51% were taking inhaled steroids and 26% were treated with cromones plus intermittent steroids. In the Oulu province, the respective prevalence was 32.7-34.9/1000, and the respective proportions were 5%, 93% and 2%. RESULTS: Total and first admissions, as well as hospital days were clearly less in the Oulu province. In the children aged > or = 6y, the average annual total admissions were 0.3/1000 (Oulu) vs 1.2/1000 (Kuopio) (p < 0.001). Similarly, the first admissions were 0.2/1000 vs 1.0/1000 (p < 0.001), proportions of readmissions 6.3% vs 19.3% (p < 0.05), and numbers of hospital days 0.7/1000 vs 3.8/1000 (p < 0.001). The differences were in the same direction, though less prominent, also among children 2-5 y of age. CONCLUSION: Our results suggest that inhaled steroids are better than cromones in preventing admissions for asthma when two provinces with different practices for maintenance medication of steady-state asthma were compared.     

Immunoregulation with Levamisole in Children with Frequently Relapsing Steroid Responsive Nephrotic Syndrome

ABSTRACT. The immunological and clinical effects of levamisole were studied in 10 children with frequently relapsing steroid responsive nephrotic syndrome (SRNS). The efficacy of the drug was tested during remission of the disease with all patients on alternate day steroid therapy. The lymphocyte proliferative response to phytohemagglutinin (PHA), concanavalin-A (Con-A) and pokeweed mitogen (PWM) were normal. The Con-A induced suppressor T-lymphocyte activity of 7 patients was low before treatment with levamisole 8±3.7% and increased to normal values during therapy 34±6%; p <0.001 (control 32±5%). In these 7 children prednisolone dosage could be decreased significantly or discontinued altogether (44.1±5.3%). Patients without immunoregulatory abnormalities did not respond to levamisole. In 3 out of 4 children tested the percentage of OKT8⁺ cells rose during levamisole therapy from 19.7±2.1 to 37±2.3 ( p <0.001), thus correcting the elevated pre-treatment OKT4⁺/OKT8⁺ ratio from 3.1±0.2 to 1.5±0.2; p <0.001 (control 1.47±0.2). These data support the hypothesis that abnormal immunoregulation may play a role in the pathogenesis of SRNS. Treatment with levamisole can be useful in some patients with the frequently relapsing form of the disease.     

Placebo controlled trial of systemic corticosteroids in acute childhood asthma

In a randomised controlled trial 38 asthmatic children aged 2-11 yr who had not received regular oral or inhaled steroids during the previous year, were treated with a standard regime of nebulised salbutamol and intravenous aminophylline plus either hydrocortisone and oral prednisolone for 5 days, or placebo. The children were observed throughout their hospital stay and for 3 months afterwards. There was a greater fall in heart rates in the steroid treated group on the second day of treatment (mean diff. 16 beats/min) and at discharge (mean diff. 13 beats/min); p less than 0.025. Peak Expiratory Flow Rates recorded in 26 children, 13 in each group, showed more improvement on day 2 in those given steroids (mean diff 16% predicted); p less than 0.05. This difference was not apparent at discharge but 9 children treated with steroids were clinically wheeze-free when they left hospital compared with 3 in the placebo group, p less than 0.05. There were no differences in respiratory rate, pulsus paradoxus and arterial oxygen saturation. Trends in duration of hospital stay and relapse rate during the succeeding 3 months favoured active treatment. These findings support the use of systemic corticosteroids in addition to high dose bronchodilators to treat 'non steroid dependent' children hospitalised with acute severe asthma.     

Differential protein clearances and response to treatment in Nigerian nephrotic children.

Remission followed prednisolone therapy in 9 out of 21 Nigerian children with the nephrotic syndrome who had highly selective proteinuria (CG/CA less than 15%). Of these, 5 patients have remained well off all treatment during a follow-up of nearly 5 years, 4 have relapsed more than once but have responded to further courses of prednisolone. 3 of 21 with less selective proteinuria also remitted but all relapsed and only one of these has responded again. The other two have relapsed and further courses of prednisolone have not totally abolished their proteinuria though they are asymptomatic and in good health. Toxicity (hypertension, sometimes with encephalopathy and infection) was commoner in the patients with less selective proteinuria treated with steroids than in those with highly selective proteinuria. 3 steroid-sensitive patients who had had repeated relapses became free from relapse off all treatment after a course of cyclophosphamide, given during steroid-maintained remission. All but 2 of the renal biopsies taken were regarded as abnormal. The lesions were less severe in those who responded than in those who did not. There is some evidence to suggest that Plasmodium malariae may be a cause of some of the steroid-sensitive disease, as well as the steroid-resistant.     

Prognosis and treatment of polymyositis with particular reference to steroid resistant patients.

Eight boys and six girls with polymyositis examined between 1967 and 1982 were studied. The mean age of disease onset was 5 years 5 months. The initial regimen was prednisolone, 1.2 to 2.3 mg/kg/day, and after four weeks this dose was decreased gradually to a maintenance level of 5 to 20 mg on alternate days. The total treatment period was 3 years 6 months on average. Eleven of the 14 children had a uniphasic course, and steroids were stopped without a resurgence of the disease: three were refractory to steroid treatment. One of these died of a cardiomyopathy seven years after the onset of the illness despite treatment with steroids and cyclophosphamide; the second was treated with adrenocorticotrophic hormone after prednisolone, but without benefit; and in the third a series of treatment with lympho-plasmapheresis and cyclophosphamide resulted in some improvement. As cardiac involvement in polymyositis may become overt if the disease persists for many years, patients refractory to steroids should be given alternative treatment.     

Corticosteroids in primary tuberculosis with bronchial obstruction.

The usefulness of prednisolone in combination with the modern potent antituberculous drugs has been studied in 29 children with primary lung tuberculosis and hilar adenopathy causing bronchial obstruction. These children were divided at random in two groups of 15 and 14 patients. Both groups were treated similarly except that one group received prednisolone. Both groups were very similar before the onset of treatment for most variables. Tuberculous infection healed in both groups but the group on steroids improved earlier and had significantly fewer complications, both on radiography and bronchoscopy. Only two of the patients on steroids still had progressive lesions: a very young baby probably because he developed two severe viral infections consecutively, and another infant of 7 months whose treatment was unreliable, as the parents were not very compliant. Some patients initially not treated with prednisolone improved only after it was given. Prednisolone treatment is not recommended when the reliability of the treatment cannot be guaranteed, as the hazard of harm would exceed the expected benefit.