Biofeedback training in treatment of childhood constipation: a randomised controlled study

BACKGROUND: Because abnormal defaecation dynamics, which can be modified by biofeedback, are considered to be the underlying problem in constipation, biofeedback training may be a useful treatment for constipation. This treatment has mainly been studied in uncontrolled trials. We evaluated defaecation dynamics and clinical outcome in chronically constipated children in a randomised study comparing conventional treatment and conventional treatment with biofeedback training. METHODS: Patients, 5 to 16 years old, were referred to the Academic Medical Center in Amsterdam by general practitioners, school doctors, paediatricians, and psychiatrists. They had to fulfil at least two of four criteria for paediatric constipation and were included if they had been treated medically for at least one month before randomisation. Patients had a medical history, abdominal and rectal examination, and anorectal manometry at the start and end of the 6-week intervention period. The conventional group received laxative treatment with additional dietary advice, toilet training, and maintenance of a diary of bowel habits. The biofeedback group received the same conventional treatment and additionally five biofeedback training sessions. During the first 3 weeks, patients visited the outpatient clinic weekly; two subsequent visits were twice monthly. FINDINGS: 94 patients were randomised to conventional treatment (CT) and 98 to conventional treatment with additional biofeedback training (CT+BF). Normal defaecation dynamics increased in the CT group from 41% to 52% (not significant) and in the CT+BF group from 38% to 86% (p = 0.001). At 6 weeks, more patients in the CT+BF group showed normal defaecation dynamics, compared to the CT group (p < 0.001). This result was unaltered by controlling for baseline status in a logistic regression model. At 1 year, successful treatment (defaecation frequency > or = 3/week, soiling and/or encopresis < 2/month, and no laxatives) was accomplished in 59% of the CT and 50% of the CT+BF group (p = 0.24). The results were maintained after 1 1/2 years follow-up. No association was found between achievement of normal defaecation dynamics and clinical outcome. INTERPRETATION: Additional biofeedback training compared to conventional therapy did not result in higher success rates in chronically constipated children. Furthermore, achievement of normal defaecation dynamics was not associated with success: abnormal defaecation dynamics seem not to play a crucial role in the pathogenesis of childhood constipation. Intensive conventional laxative treatment should remain the first choice in chronically constipated children.     

Evidence that cellular immune responses to soluble and membrane associated antigens are independently regulated during human schistosomiasis mansoni

The glucagonoma syndrome is a rare disorder characterized by weight loss, necrolytic migratory erythema (NME), diabetes, stomatitis, and diarrhea. We identified 21 patients with the glucagonoma syndrome evaluated at the Mayo Clinic from 1975 to 1991. Although NME and diabetes help identify patients with glucagonomas, other manifestations of malignant disease often lead to the diagnosis. If the diagnosis is made after the tumor is metastatic, the potential for cure is limited. The most common presenting symptoms of the glucagonoma syndrome were weight loss (71%), NME (67%), diabetes mellitus (38%), cheilosis or stomatitis (29%), and diarrhea (29%). Although only 8 of the 21 patients had diabetes at presentation, diabetes eventually developed in 16 patients, 75% of whom required insulin therapy. Symptoms other than NME or diabetes mellitus led to the diagnosis of an islet cell tumor in 7 patients. The combination of NME and diabetes mellitus led to a more rapid diagnosis (7 months) than either symptom alone (4 years). Ten patients had diabetes mellitus before the onset of NME. No patients had NME clearly preceding diabetes mellitus. Increased levels of secondary hormones, such as gastrin (4 patients), vasoactive intestinal peptide (1 patient), serotonin (5 patients), insulin (6 patients, clinically significant in 1 only), human pancreatic polypeptide (2 patients), calcitonin (2 patients) and adrenocorticotropic hormone (2 patients), contributed to clinical symptoms leading to the diagnosis of an islet cell tumor before the onset of the full glucagonoma syndrome in 2 patients. All patients had metastatic disease at presentation. Surgical debulking, chemotherapy, somatostatin, and hepatic artery embolization offered palliation of NME, diabetes, weight loss, and diarrhea. Despite the malignant potential of the glucagonomas, only 9 of 21 patients had tumor-related deaths, occurring an average of 4.91 years after diagnosis. Twelve patients were still alive, with an average age follow-up of 3.67 years.     

Release of superoxide anion from activated mouse peritoneal macrophages during Mycobacterium tuberculosis infection

Mouse peritoneal macrophage monolayers infected with M. tuberculosis were cultured in RPMI up to 7 days. Release of superoxide was assayed on different days in presence or absence of Phorbol myristate acetate (PMA), a known stimulator of NADPH oxidase which is involved superoxide production. Basal level of superoxide release was significantly higher in M. tuberculosis infected peritoneal mouse macrophages (P < 0.01) as compared to normal mouse macrophages. When normal and tuberculoid macrophage cultures were stimulated with PMA, increased superoxide anion release was observed in both the cultures but the increase of superoxide was significantly higher in normal macrophages as compared to tuberculoid stimulated macrophages. Superoxide release was maximum in 4 day old cultured macrophages and gradually it declined in older cultures by day 7, both in vitro and in vivo. A defective macrophage function in killing of M. tuberculosis bacilli was observed after 4 days of in vitro and in vivo cultures.     

Tetracycline inhibition and the cellular source of collagenase in gingival crevicular fluid in different periodontal diseases. A review article

The effectiveness of bibliotherapy as an adjunct to stimulant medication in the treatment of children with attention-deficit hyperactivity disorder was investigated. Subjects were randomly assigned to the experimental group, or the control group. Parents in the experimental group received a written protocol (bibliotherapy) outlining behavioral techniques for managing oppositional child behavior. Results indicated significant differences favoring the experimental group on standardized measures of the intensity of behavior problems in the home, parental knowledge of behavioral principles, and teacher ratings of behavior. This bibliotherapy approach appears to offer an inexpensive adjunct to stimulant medication in the treatment of attention-deficit hyperactivity disorder when individual or group behavior management training is not feasible.     

Tumor efficacy and bone marrow-sparing properties of TER286, a cytotoxin activated by glutathione S-transferase

TER286 is a latent drug activated by human glutathione S-transferase (GST) isoforms P1-1 and A1-1 to produce a nitrogen mustard alkylating agent. M7609 human colon carcinoma, selected for resistance to doxorubicin, and MCF-7 human breast carcinoma, selected for resistance to cyclophosphamide, both showed increased sensitivity to TER286 over their parental lines in parallel with increased expression of GST P1-1. In primary human tumor clonogenic assays, the spectrum of cytotoxic activity observed for TER286 was both broad and unusual when compared to a variety of current drugs. In murine xenografts of M7609 engineered to have high, medium, or low GST P1-1, responses to TER286 were positively correlated with the level of P1-1. Cytotoxicity was also observed in several other cell culture and xenograft models. In xenografts of the MX-1 human breast carcinoma, tumor growth inhibition or regression was observed in nearly all of the animals treated with an aggressive regimen of five daily doses. This schedule resulted in a 24-h posttreatment decline in bone marrow progenitors to 60% of control and was no worse than for a single dose of TER286. These studies have motivated election of TER286 as a clinical candidate.     

Reversal of advanced liver fibrosis in rabbits with Schistosomiasis japonica

Advanced liver fibrosis is generally considered to be irreversible. We studied the reversibility of marked liver fibrosis in rabbits infected with Schistosoma japonicum. We determined liver collagen content, collagen biosynthesis, and collagenase activity using serial biopsy specimens obtained 20, 40, and 60 weeks after infection. Reversibility of this process was investigated in rabbits cured of infection at 21 weeks; control rabbits not cured of infection were also studied. At 20 weeks, liver collagen content was 16-fold greater than normal, with accumulation of collagen types I, III, and V. Synthesis of collagen within fibrotic liver slices was 10-fold greater than normal. Liver collagenolytic activity for a type I substrate was 19-fold greater than normal. After parasitologic cure, a striking morphologic reversal of fibrosis occurred during the subsequent 40 weeks, with the return of liver collagen content to three-fold greater than normal and a 75% decrease in synthetic rates compared with those at 20 weeks (P < 0.01). Collagenolytic activity remained elevated to the same degree noted at 20 weeks. A similar but lesser resolution of fibrosis also occurred in untreated control rabbits, coincident with a spontaneous decrease in new egg deposition known to occur in this model system. We conclude that advanced liver fibrosis in S. japonicum-infected rabbits is slowly reversible after cure or senescence of the infection. A possible mechanism for this reversal is persistently increased collagenolysis as collagen synthesis diminishes.