Long-term treatment with autologous red blood cells loaded with dexamethasone 21-phosphate in pediatric patients affected by steroid-dependent Crohn disease.

BACKGROUND: Inflammatory bowel disease (IBD) present in childhood in 15% to 25% of cases. The aim of therapy in children is not only to guarantee normal growth but also to prevent relapse and to maintain remission. Steroids are effective to induce remission; however, resistance, dependency, and irreversible side effects can develop. The aim of this study was to determine whether treatment with repeated infusions of autologous red blood cells (RBCs) loaded with dexamethasone 21-phosphate (Dex 21-P) is safe and allows maintenance of long-term remission in children with steroid-dependent Crohn disease (CD). PATIENTS AND METHODS: Eighteen consecutive pediatric patients who met the inclusion criteria were admitted to the study. Infusions of autologous RBCs loaded with Dex 21-P were performed every 4 weeks; the mean duration of treatment was 24 months. At the beginning of treatment and after 6, 12, and 24 months, we performed clinical evaluation according to the Pediatric Crohn Disease Activity Index (pCDAI). Assessment of body mass in dexamethasone and bone mineral density by means of computerized bone mineralometry-dual energy x-ray absorptiometry, endoscopic evaluation, and hematic morning cortisol determination were also performed. RESULTS: During treatment, the mean pCDAI significantly decreased (P < 0.05); 78% of patients discontinued steroids. Determination of morning cortisol showed suppression only on the first day after infusion, followed by normalization of values. Endoscopic findings showed remission in 44% of patients. None of the patients experienced serious side effects. CONCLUSIONS: These data suggest that repeated infusions of RBCs loaded with Dex 21-P can be safe and useful to maintain long-term remission in pediatric patients with moderately active CD.

Chronic constipation in hemiplegic patients.

AIM: To assess the prevalence of bowel dysfunction in hemiplegic patients, and its relationship with the site of neurological lesion, physical immobilization and pharmacotherapy. METHODS: Ninety consecutive hemiplegic patients and 81 consecutive orthopedic patients were investigated during physical motor rehabilitation in the same period, in the same center and on the same diet. All subjects were interviewed >= 3 mo after injury using a questionnaire inquiring about bowel habits before injury and at the time of the interview. Patients' mobility was evaluated by the Adapted Patient Evaluation Conference System. Drugs considered for the analysis were nitrates, angiogenic converting enzyme (ACE) inhibitors, calcium antagonists, anticoagulants, antithrombotics, antidepressants, anti-epileptics. RESULTS: Mobility scores were similar in the two groups. De novo constipation (OR = 5.36) was a frequent outcome of the neurological accident. Hemiplegics showed an increased risk of straining at stool (OR: 4.33), reduced call to evacuate (OR: 4.13), sensation of incomplete evacuation (OR: 3.69), use of laxatives (OR: 3.75). Logistic regression model showed that constipation was significantly and independently associated with hemiplegia. A positive association was found between constipation and use of nitrates and antithrombotics in both groups. Constipation was not related to the site of brain injury. CONCLUSION: Chronic constipation is a possible outcome of cerebrovascular accidents occurring in 30% of neurologically stabilized hemiplegic patients. Its onset after a cerebrovascular accident appears to be independent from the injured brain hemisphere, and unrelated to physical inactivity. Pharmacological treatment with nitrates and antithrombotics may represent an independent risk factor for developing chronic constipation.

Long-term parenteral nutrition in pediatric autoimmune enteropathies.

Severe and protracted or persistent diarrhea (SPD) is the most severe form of diarrhea in infancy and has also been defined as intractable diarrhea when it leads to dependence on total parenteral nutrition (TPN). One of the rare causes of SPD is represented by autoimmune enteropathy that is characterized by life-threatening diarrhea mainly occurring within the first years of life, persistent villous atrophy in consecutive biopsies, resistance to bowel rest, and evidence of antigut autoantibodies. We evaluated 10 patients (seven boys, mean age at diagnosis 18 months; range: 0 to 160 months) fulfilling criteria of autoimmune enteropathy to assess dependence on TPN. TPN was first required in all patients to avoid dehydration and electrolytic imbalance. All patients were dependent on immunosuppressive therapy (steroid, azothioprine, cyclosporine, tacrolimus). Three patients died of sepsis: two during TPN while in the hospital, and one at home after he was weaned off TPN. Five patients are weaned off TPN after a mean period of 18 months; they are actually on oral alimentation with a cow milk-free diet after a period of enteral nutrition with elemental formula. One underwent total colectomy and bone marrow transplantation and one developed an IPEX syndrome. One patient is still dependent on TPN for 24 months. She is on home parenteral nutrition. Patients with diagnosis of IPEX syndrome require parenteral support with three or four infusion per week. TPN represents a fixed step in the management of autoimmune enteropathy, but it may be considered as an interim treatment while waiting for intestinal adaptation, at least in some selectioned case of autoimmune enteropathy. Bone marrow transplantation should be considered and reserved for those patients with severe complications due to home parenteral nutrition, or in those that are really dependent on parenteral nutrition.

Ranitidine and somatostatin. Their effects on bleeding from the upper gastrointestinal tract.

In a randomized, double-blind placebo-controlled clinical trial, the effect of ranitidine was compared with the effect of somatostatin in the control of massive gastrointestinal tract bleeding. Ninety-six patients completed the study. Rates of continuing bleeding and death, incidence of surgery, and blood transfusion requirements were not significantly different in the three treatment groups. Eighteen of the 96 patients presented with a visible vessel at endoscopy. In this group the percent of patients with continuing bleeding, mean transfusion requirements, and mortality were significantly higher than in patients without a visible vessel. Seven patients with a visible vessel underwent surgery and six survived; 11 patients underwent conservative measures and eight died. Ranitidine and somatostatin do not seem to alter the clinical course of patients with upper gastrointestinal tract hemorrhage.

Structure of biliary phosphatidylcholine in cholesterol gallstone patients.

The fatty acid composition of biliary phosphatidylcholine was analyzed in 13 patients with radiolucent gallstones undergoing elective cholecystectomy, and in 11 normolipemic patients without gallstone undergoing abdominal surgery. The only difference in the percentage fatty acid composition between the two groups was a significantly (p less than 0.05) higher percentage arachidonic acid in the first group. This acid was exclusively located in the sn-2 position of phosphatidylcholine (PC), accounting for 13.0 +/- 4.9% in the first group and 8.2 +/- 4.9% in the second (p less than 0.05). The percentage arachidonic acid of PC was negatively correlated (p less than 0.001) with the percentage biliary chenodeoxycholate in gallstone patients, but not in controls. Explanation of these findings is, at present, only speculative.

Preliminary report of electrogastrography in pediatric gastroresection: can it be predictive of alteration of gastric motility?

BACKGROUND/PURPOSE: Gastric resection is an infrequent surgical procedure in childhood. However, the use of the stomach for bladder augmentation and substitution is well documented. Partial gastrectomy performed in gastrocystoplasty (GCP) involves the greater curvature of the stomach, the same area in which gastric pace-maker cells are known to be placed. The aim of this study was to assess, by electrogastrography (EGG), if subtotal gastric resection can alter gastric motility in children submitted to partial gastrectomy for GCP. METHODS: Gastric electrical activity (GEA) was evaluated in 25 children using EGG: 10 patients (4 boys, 6 girls; mean age, 11.6 years) previously submitted to GCP, and 15 normal subjects (12 boys, 3 girls; mean age, 8.62 +/- 2.77 years) as controls. All patients were submitted to cutaneous EGG; recording GEA for 30 minutes before and after a standard test meal. The percentage of 3 cycles per minute (3CPM), bradygastria, tachygastria, DFIC (dominant frequency instability coefficient), DPIC (dominant power instability coefficient), PDP (period dominant power), PDF (period dominant frequency) were recorded and analyzed using Wilcoxon matched-pair test. Data were considered statistically significant if P <.05. RESULTS: Normal subjects as well as operated patients showed a statistically significant difference in bradygastria (P =.05), PDP and PDF (P =.05) percentage, comparing pre versus postprandial period. In the normal group, 3CPM (P =.0012) and DFIC (P =.0008) were statistically different between the pre- and postprandial period. Patients who underwent GCP did not show any statistically significant difference in 3CPM and DFIC pre- and postprandial. CONCLUSIONS: In normal subjects, GEA showed a complete variation after the meal, whereas in operated patients GEA was impaired and only partially modified after the meal. This observation suggests that in patients with gastric resection, adaptation of the stomach to food ingestion is present but incomplete with respect to normal subjects; it can be caused by surgical removal of the pace-maker cells of the greater curvature. For this reason a follow-up analysis of gastric function is recommended for all patients undergoing GCP.

Role of electrogastrography in detecting motility disorders in children affected by chronic intestinal pseudo-obstruction and Crohn's disease.

Gastrointestinal motility disorders are frequently found in several pathologies. The aim of this study was to assess, by means of electrogastrography, the presence of gastrointestinal motility abnormalities in children affected by Crohn's disease (CD) or Chronic Intestinal Pseudo-Obstruction (CIPO). Patients and Methods. We studied 34 subjects; 20 control subjects (M = 15, mean age = 10 +/- 3.5 yrs), 8 patients (M = 4, mean age = 18 +/- 7 yrs) with Crohn's disease in a quiescent phase and 6 patients (M = 6, mean age = 10 +/- 3.5 yrs) with Chronic Intestinal Pseudo-Obstruction. Results. Analysis of gastric electrical activity (GEA) parameters demonstrated that in the control group physiological post-prandial changes are represented by an increase of 3 Cycles Per Minute (3 CPM) activity, Period Dominant Power (PDP) and Period Dominant Frequency (PDF) and by the reduction of bradygastria. Crohn patients showed an insignificant increase of 3 CPM and PDP; CIPO patients showed an abnormal variation of 3 CPM, PDP and post-prandial bradygastria. Moreover, CD patients showed a significant difference in post-prandial values of PDP compared to normal subjects. CIPO patients revealed a significant difference in the values of either preprandial PDF with tachygastria or the post-prandial value of 3 CPM, compared to normal subjects. Conclusions. EEG is a non-invasive method to study gut motility related to GEA alterations present in CIPO as well as in CD patients.

[Return to the home environment and to work of the patient treated with portacaval anastomsosis]. / Sul reinserimento nell'ambiente familiare e di lavoro dell'operato di anastomosi porto-cava.

Social and occupational reinsertion is examined with reference to a series of 137 patients subjected to side-to-side porto-cava anastomosis for portal hypertension due to cirrhosis of the liver. Postoperative occupational reinstatement was possible in a group of patients (39.42%) who had been compelled to work less on account of haemorrhages. Considering the seriousness of the operation and the long convalescence required, there was a good overall recommencement of occupational activity (73.72%). The view is expressed that continuous contact with the hospital is essential, since this will more readily ensure that the basic hygienic and dietetic rules applicable to the patient are respected. In addition, it is felt that the patient should be required to lead as normal a life as possible, in spite of his underlying liver alteration.

[The Denver peritoneojugular shunt. Current indications]. / Shunt peritoneo-giugulare sec. Denver. Attuale indicazione.

Personal experience of 31 patients suffering from intractable ascites due to advanced liver cirrhosis between 1978 and 1987 is reported. Seventeen patients were selected for a peritoneojugular shunt: in 3 patients the Le Veen shunt was performed and in 14 the Denver shunt was preferred. The high postoperative morbidity and mortality due to liver failure, DIC, hepatorenal syndrome, bleeding, sepsis and cerebral thrombosis is pointed out. Careful selection of patients to be submitted to this surgical procedure is essential because of the high morbidity due to ascites reinfusion. DIC has to be diagnosed as soon as possible and, when severe, the prompt interruption of the peritoneojugular shunt is mandatory.

[Assessment of platelet survival before and after latero-lateral portacaval shunt]. / La valutazione della sopravvivenza piastrinica prima e dopo shunt porto-cavale latero-laterale.

On the basis of a group of 175 patients affected by liver cirrhosis and submitted to side-to-side porto-caval shunt, we have examined the presence of hypersplenism in 49.7% and its changes after splenectomy. In order to find out a suitable method to value the changes of the platelets, we observed platelet survival in seven patients either before or after porto-caval shunt. The results obtained encourage in affirming that: 1) Hypersplenism improves after a simple shunt. 2) Hypersplenism is not severe even if it persists with an open shunt. 3) The possible onset of shunt thrombosis worsens hypersplenism. 4) Platelet survival is surely effective in the study of hypersplenism.

Operative morbidity after shunt surgery for portal hypertension.

The operative morbidity observed in a consecutive series of 286 patients who underwent shunt surgery for portal hypertension is reported. 149 patients out of 286 (52.1%) had a postoperative complication, which required reoperation in 11 cases (5 intestinal perforations, 2 bleeding peptic ulcers, 1 eventratio, 1 cholestasis, 1 acute pancreatitis, 1 strangulated hernia). 42 patients out of the 149 with complications died of the complication (operative mortality 14.6%). Operative morbidity and mortality appeared higher in patients operated as emergencies. Whereas elective shunts gave better results. The problem involved in preventing and treating the serious complications following shunt surgery for portal hypertension are discussed.

[Lymphovenous anastomosis in severe ascites]. / L'anastomosi linfovenosa nell'ascite difficile.

The authors dealt with 37 patients suffering from advanced liver cirrhosis with ascites. Eighteen patients out of them underwent Denver peritoneum-jugular shunt as a first choice procedure, the other 19 patients underwent lymphovenous anastomosis. The extremely advanced hepatic damage and the general conditions of these patients discouraged us to perform a portocaval shunt. In the 19 patients who underwent lymphovenous anastomosis we had no mortality rate. Two patients showed post-operative complications: 1 patient complained which hoarseness regressed in 5 months and the other patient suffered from a spleno-mesenteric-portal thrombosis with digestive hemorrhage from gastro-esophageal varices. In 6 patients out of 19 who underwent lymphovenous anastomosis, we did not obtain any immediate positive effects on ascites. In 4 patients, after 3 months, the ascites came back ingravescent and in the other 9 patients the positive effects on ascites were still evident after 1 year. Despite failure to obtain very comforting results, they suggest to employ this technique at any rate, as the first procedure, to make ascites more "manageable", because of its safety.

Thalidomide as rescue therapy for acute severe ulcerative colitis.

INTRODUCTION: Acute severe exacerbations of Ulcerative Colitis (UC) represent a medical emergency in children and adults. Intravenous steroids remain the first line therapy for this condition, although the steroid refractoriness is common. Second-line therapy, based on the infliximab or thiopurines should be started if no response to corticosteroids is noted. The use of infliximab in children with acute severe UC, nevertheless, does not avoid the colectomy in all cases. METHODS: We present a case of severe acute UC in a paediatric patient successfully treated with thalidomide following the failed treatment with infliximab and a review of the literature. CONCLUSIONS: This is the first case of a patient presenting with acute severe UC who was treated with thalidomide, with favorable evolution. In our case the use of this drug was able to avoid the colectomy that represent the conventional but very invasive recommended therapeutic option of this condition. Therefore, thalidomide may be considered as rescue therapy in selected and carefully monitored cases of acute severe CU.

Association between celiac disease and primary lactase deficiency.

Primary lactase deficiency (PLD) is a common inherited condition caused by a reduced activity of lactase. Two single-nucleotide polymorphisms C/T(-13910) and G/A(-22018) upstream of the lactase gene are associated with lactase nonpersistence. In celiac disease (CD) patients, lactose intolerance could be due to secondary lactase deficiency and to PLD. The aim of this study were to evaluate the association of PLD and CD using genetic test, and to define the prevalence of PLD in celiac subjects compared with a control population. A total of 188 controls and 92 biopsy-proven CD patients were included in the study. More than 70% of all subjects were found homozygous for the polymorphisms. Differences in the prevalence of PLD were not found between CD patients and controls.In conclusions, the hereditary lactase deficiency is frequent in Italian CD children as in control population.

Diagnostic work-up of inflammatory bowel disease in children: the role of calprotectin assay.

BACKGROUND: Some reports highlight the potential application of fecal calprotectin as a direct biomarker of intestinal inflammation and, therefore, as support in choosing candidates for endoscopy. The value of 100 µg/g was recently assumed as the best cutoff for this assay. The purpose of this study was to assess the diagnostic precision of the fecal calprotectin assay, compared to histology, as a stool-screening biomarker for inflammatory bowel disease (IBD) among a group of prospectively identified patients referred for recurrent abdominal pain and altered bowel habits. METHODS: Between 1999 and 2007 we prospectively evaluated the calprotectin assay in a cohort of patients with recurrent abdominal pain and altered bowel habits associated or not with other symptoms suggestive of IBD. All patients suspected of IBD, according to Rome and Porto criteria, provided stool specimens for the calprotectin assay and subsequently underwent endoscopic procedures. RESULTS: Compared to histology, the cutoff of 100 µg/g reached a sensitivity and specificity of 100% and 68%, respectively, and a likelihood ratio (LR) of 3.1. The cutoff value of 160 µg/g, however, in our series produced the best joint estimate of sensitivity and specificity: 100% and 80%, respectively, with an LR of 5. CONCLUSIONS: In pediatric patients with recurrent abdominal pain and changes in stool habits, a positive calprotectin assay is closely associated with IBD; its systematic employment, therefore, seems to improve the process of endoscopy referral. This test, simple and inexpensive, could be included in the first noninvasive phase of an IBD diagnostic work-up.