Colonic and anorectal function in constipated patients with anorexia nervosa

OBJECTIVES: Many patients with eating disorders complain of severe constipation. Previous studies have suggested that constipation in patients with anorexia nervosa may be associated with slow colonic transit. However, it is unclear whether a refeeding program will alter colonic transit in these patients. The aim of this study was to investigate colorectal function by measuring colonic transit and anorectal function in anorexic patients with constipation during treatment with a refeeding program. METHODS: We prospectively studied 13 female patients with anorexia nervosa who were admitted to an inpatient treatment unit and compared them to 20 previously studied, age-matched, healthy female control subjects. Patients underwent colonic transit studies using a radiopaque marker technique and anorectal manometry measuring anal sphincter function, rectal sensation, expulsion dynamics, and rectal compliance. Patients were studied both early (< 3 wk) and late (> 3 wk) in their admission. We restudied two patients who had slow colonic transit. All patients also underwent structured interviews. RESULTS: Four of six patients studied within the first 3 wk of their admission had slow colonic transit, defined as > 70 h (108.0 +/- 17.0 h, mean +/- SEM), on initial evaluation. In contrast, none of the seven patients studied later than 3 wk into their admission had slow colonic transit. Two of the four patients with slow transit were restudied later in their admission and were found to have normal transit times. Rectal sensation, internal anal sphincter relaxation threshold, rectal compliance, sphincter pressures, and expulsion pattern were normal in all subjects. CONCLUSIONS: Despite complaints of severe constipation, colonic transit is normal or returns to normal in the majority of patients with anorexia nervosa once they are consuming a balanced weight gain or weight maintenance diet for at least 3 wk.     

Failure to cure Mycobacterium gordonae peritonitis associated with continuous ambulatory peritoneal dialysis

Nontuberculous mycobacteria are increasingly recognized as important pathogens in peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD). Mycobacterium gordonae rarely causes human infection and is the least likely mycobacterium to produce clinical infection in CAPD patients. We describe a patient with persistent M. gordonae peritonitis acquired while undergoing CAPD. During 18 months of treatment, clinical improvement occurred but a microbiological cure could not be achieved. Principles of therapy for mycobacterial peritonitis developing during CAPD are reviewed, and potential explanations for our patient's failure to respond to therapy are discussed.     

Meshlaparostomy--a comparison between polypropylene mesh and indigenous nylon net

Polypropylene mesh, the routinely used material for mesh laparostomies is expensive. A economical and easily available substitute-nylon net was compared with polypropylene mesh with regard to efficacy and wound complications in a retrospective study. 51 patients, 25 in the polypropylene mesh group and 26 in the nylon net group were studied. The groups were matched with respect to age, sex, indication for surgery and mortality. The mean hospital stay (65 vs 54 days), fate of the wound, incidence of mesh extrusion (26% vs 20%), bowel perforation (1 vs none) and incisional hernia formation (21% vs 20%) in those with polypropylene mesh and nylon net respectively was similar. In conclusion, nylon net is an effective and inexpensive indigenous substitute for polypropylene mesh for mesh laparostomies.     

The surface of Toxoplasma tachyzoites is dominated by a family of glycosylphosphatidylinositol-anchored antigens related to SAG1

Toxoplasma gondii is an Apicomplexan parasite with a complex life cycle that includes a rapidly dividing asexual stage known as the tachyzoite. The tachyzoite surface has been reported to comprise five major antigens, the most abundant of which is designated SAG1 (for surface antigen 1). At least one of the other four (SAG3) and another recently described minor antigen (SRS1 [for SAG1-related sequence 1]) have previously been shown to be structurally related to SAG1. To determine if further SAG1 homologs exist, we searched a Toxoplasma expressed sequence tag (EST) database and found numerous ESTs corresponding to at least three new genes related to SAG1. Like SAG1, these new SRS genes encode apparently glycosylphosphatidylinositol-anchored proteins that share several motifs and a set of conserved cysteine residues. This family appears to have arisen by divergence from a common ancestor under selection for the conservation of overall topology. The products of two of these new genes (SRS2 and SRS3) are shown to be expressed on the surface of Toxoplasma tachyzoites by immunofluorescence. We also identified strain-specific differences in relative expression levels. A total of 10 members of the SAG1 gene family have now been identified, which apparently include three of the five major surface antigens previously described and one antigen expressed only in bradyzoites. The function of this family may be to provide a redundant system of receptors for interaction with host cells and/or to direct the immune responses that limit acute T. gondii infections.     

p53 and K-ras status in duodenal adenomas in familial adenomatous polyposis

BACKGROUND: The genetic alterations in patients with familial adenomatous polyposis (FAP) and duodenal adenomas are poorly characterized when compared with data relating to colorectal tumorigenesis in the same patients. METHODS: Point mutation of the K-ras oncogene and point mutation and overexpression of the TP53 tumour suppressor gene were investigated in 32 duodenal polyps (seven without mucosal pathology, 23 with mildly dysplastic adenomas and two with moderately dysplastic adenomas) from 21 patients with FAP. RESULTS: K-ras mutation, TP53 mutation or positive p53 staining were not found in duodenal polyps without histological abnormality. Of 25 duodenal adenomas, K-ras mutation was found in three (two mildly dysplastic, one moderately dysplastic), 20 showed positive p53 immunostaining, and mutation of the TP53 gene was found in one moderately dysplastic adenoma. p53 protein overexpression in duodenal adenomas was significantly more frequent than mutation of either K-ras or TP53 (P < 0.01). CONCLUSION: p53 dysfunction is a hallmark of duodenal adenomas in patients with FAP. Overexpression may indicate DNA damage and thus an early step in tumorigenesis.     

Are supplementary services provided during methadone maintenance really cost-effective?

OBJECTIVE: Previous research has suggested that support services supplementing methadone maintenance programs vary in their cost-effectiveness. This study examined the cost-effectiveness of varying levels of supplementary support services to determine whether the relative cost-effectiveness of alternative levels of support is sustained over time. METHOD: A group of 100 methadone-maintained opiate users were randomly assigned to three treatment groups receiving different levels of support services during a 24-week clinical trial. One group received methadone treatment with a minimum of counseling, the second received methadone plus more intensive counseling, and the third received methadone plus enhanced counseling, medical, and psychosocial services. The results at the end of the trial period have been published elsewhere. This article reports the results of an analysis at a 6-month follow-up. RESULTS: The follow-up analysis reaffirmed the preliminary findings that the methadone plus counseling level provided the most cost-effective implementation of the treatment program. At 12 months, the annual cost per abstinent client was $16,485, $9,804, and $11,818 for the low, intermediate, and high levels of support, respectively. Abstinence rates were highest, but modestly so, for the group receiving the high-intensity, high-cost methadone with enhanced services intervention. CONCLUSIONS: This study suggests that large amounts of support to methadone-maintained clients are not cost-effective, but it also demonstrates that moderate amounts of support are better than minimal amounts. As funding for these programs is reduced, these findings suggest a floor below which supplementary support should not fall.     

Oral administration of rapamycin and cyclosporine differentially alter intestinal function in rabbits

The immunosuppressive drugs rapamycin (Rap) and cyclosporine A (CsA) are used clinically to modify or abolish immune-mediated functions. This study examined the effect of orally administered regimens of Rap, CsA, and a combination of Rap/CsA on intestinal function in male New Zealand white rabbits. Animals received oral doses of CsA (15 mg/kg/body weight/day), low-dose (LD) and high-dose (HD) Rap (0.25 or 1 mg/kg/body wt/day, respectively), or Rap/CsA (0.25 and 5 mg/kg/body wt/day, or 0.5 and 5 mg/kg/body wt/day, respectively) for 20 days. We measured in vitro uptake of nutrients and permeability, and morphometric measurements in the jejunum and ileum were made. Animals receiving HD-Rap or HD-Rap/CsA had decreased food intake, body weight, and intestinal weight, when compared with LD-Rap, LD-Rap/CsA, CsA, or controls. The maximal transport rate (Vmax) for the active jejunal uptake of D-glucose was increased in HD-Rap and CsA, but not in the HD-Rap/CsA-treated animals. The jejunal Vmax of D-glucose in the LD-Rap- or -Rap/CsA-treated animals was no different from controls. In the HD-Rap- and HD-Rap/ CsA-treated animals, jejunal rates of uptake of stearic, linoleic, and linolenic acids were reduced when compared with controls. Jejunal and ileal permeability (as assessed by the passive uptake of L-glucose, tissue conductance, and mucosal-to-serosal flux of [3H]inulin) was increased in animals treated with HD-Rap or HD-Rap/CsA, when compared with CsA or controls. These parameters of permeability were no different at lower doses of Rap or Rap/CsA. The jejunal and ileal villous surface area was increased in CsA, but decreased in HD-Rap or HD-Rap/CsA animals. Thus, HD-Rap given alone or in combination with CsA reduced body weight gain, in part due to reduced food intake and malabsorption of lipids, which was due at least in part to reduced intestinal surface area. The relevance of these findings to patients undergoing chronic immunosuppressive drug therapy needs to be established.     

Osteopontin in chronic puromycin aminonucleoside nephrosis

Increased expression of osteopontin (OPN) associated with interstitial monocyte infiltration has been demonstrated in the early phase of a variety of experimental renal diseases. Whether these changes occur in the chronic phase of progressive glomerular disease is unknown. Chronic puromycin aminonucleoside nephrosis (PAN) was induced in 16 rats by the injection of a single bolus of PA into the internal jugular vein, which results in a triphasic disease characterized by minimal glomerular change and marked proteinuria, peaking at about 10 to 14 d and subsiding by 28 d, followed by a quiescent 4-wk period of no or minimal proteinuria and then the development of progressive focal glomerulosclerosis (FGS) and increasing proteinuria. Fifteen rats injected similarly with normal saline served as controls. At 11 d after injection, PA rats demonstrated significantly greater urinary protein excretion (P = 0.0107), cortical tubular OPN expression (P = 0.0086), and intraglomerular (P = 0.0009) and interstitial (P = 0.0212) monocyte infiltration than did the controls. At 42 d, no significant differences between the two groups with respect to the above parameters were detected. At 98 d, PA rats had FGS and showed a definite trend to increased proteinuria, cortical tubular OPN, and intraglomerular monocyte infiltration. Although the cortical interstitial monocyte count was not elevated in PA rats compared with controls, there were significantly more monocytes around OPN-positive cortical tubules than around OPN-negative ones (P = 0.0011). Cortical tubular OPN expression correlated well with urinary protein excretion (r = 0.932, P < 0.0001), cortical tubular proliferating cell nuclear antigen (r = 0.796, P < 0.0001), and intraglomerular monocyte count (r = 0.552, P = 0.0013). The results are consistent with a monocyte chemoattractant role for OPN and suggest that OPN is upregulated in the chronic phase of PAN and that this increase in expression is a result of glomerular events.