Therapy of severe aplastic anemia in young adults and children with allogeneic bone marrow transplantation

During an 8-year period, 28 young adults (median age 27 years) and 30 children (median age 10 years) with severe aplastic anemia have received allogeneic bone marrow transplantation (BMT) from major histocompatibility locimatched sibling donors after preparation with cyclophosphamide and total lymphoid irradiation (TLI). All recipients were previously transfused. Comparison of post-bone marrow transplantation events in adults and children reveals equivalent median time to engraftment, median duration of hospitalization, median Karnofsky assessment of activity, and equivalent low rejection rate. Although the incidence of moderate and severe acute graft-v-host disease (GVHD) and of extensive chronic GVHD was greater in adults than in children, the projected survival at 4 years of adults (67%; 95% confidence interval [CI] 49% to 85%) and of children (73%; 95% CI 57% to 89%) was equivalent. All survivors are transfusion-free and have normal peripheral blood counts. One of 28 adults and 2 of 30 children have experienced rejection, and 1 of these patients survives after a second transplant. No malignancies have been identified following transplantation. An unexpectedly high incidence of hypothyroidism has been detected and may be attributable to preparation of recipients with TLI. Therapy of severe aplastic anemia with allogeneic BMT after preparation with cyclophosphamide and TLI offers a high rate of transfusion-free survival and a low rejection rate in previously transfused young adults and children.     

Serological,genetic and clinical associations with increased health‐care resource utilization in inflammatory bowel disease

OBJECTIVE

Inflammatory bowel diseases (IBD) are associated with significant morbidity and economic burden. The variable course of IBD creates a need for predictors of clinical outcomes and health resource utilization (HRU) to guide treatment decisions. We aimed to identify clinical, serological or genetic markers associated with inpatient resource utilization in patients with ulcerative colitis (UC) and Crohn's disease (CD).

METHODS

Patients with IBD with available genetic and serological data who had at least one emergency department visit or hospitalization in a 3‐year period were included. The primary outcome measure was HRU, as measured by the All Patient Refined Diagnosis Related Group classification system. Univariate and multivariate linear and logistic regression models were used to identify the associations with HRU.

RESULTS

Altogether 858 (562 CD and 296 UC) patients were included. Anti‐CBir1 seropositivity (P = 0.002, effect size [ES]: 0.762, 95% confidence interval [CI] 0.512–1.012) and low socioeconomic status (P = 0.005, ES: 1.620 [95% CI 1.091–2.149]) were independently associated with a high HRU. CD diagnosis (P = 0.006, ES: –0.701 [95% CI –0.959 to –0.443]) was independently associated with a low inpatient HRU.

CONCLUSION

In patients with IBD who required at least one emergency department visit or hospitalization, anti‐CBir1 antibody status may be a useful biomarker of HRU when formulating management strategies to reduce disease complications and resource utilization.     

Quantitative estimations of the contribution of different bile acid pathways to total bile acid synthesis in the rat

BACKGROUND & AIMS: Cholesterol degradation to bile acids occurs via "classic" or "alternative" bile acid biosynthetic pathways. The aim of this study was to assess the contributions of these two pathways to total bile acid synthesis in vivo. METHODS: Rats with biliary fistulas were infused with squalestatin for 24 and 48 hours; specific activities of cholesterol 7 alpha-hydroxylase (C7 alpha H) and sterol 27- hydroxylase (S27H) and rates of bile acid synthesis were determined. RESULTS: Continuous squalestatin infusion (15 micrograms/h) decreased C7 alpha H specific activities to 4% and 12% of paired biliary fistula controls at 24 and 48 hours, respectively (P < 0.05) without any changes in S27H specific activities (82% and 95% of controls). At 24 hours, bile acid synthesis decreased to 43% (P < 0.05) but returned to 87% at 48 hours (P = NS). Cholic acid synthesis decreased at 24 hours but returned to control levels at 48 hours. Similar changes in C7 alpha H, S27H, and bile acid synthesis were observed in primary rat hepatocytes after addition of squalestatin (1.0 mumol/L). CONCLUSIONS: In the face of persistent suppression of C7 alpha H and the classic pathway, an alternative pathway becomes a main pathway of bile acid synthesis capable of generating cholic and chenodeoxycholic acids. The observed induction of bile acid synthesis via an alternative pathway or pathways represents an important mechanism for maintenance of cholesterol homeostasis in the rat. (Gastroenterology 1997 Dec;113(6):1949-57)     

7 alpha-dehydroxylating bacteria enhance deoxycholic acid input and cholesterol saturation of bile in patients with gallstones

BACKGROUND & AIMS: Excessive deoxycholic acid (DCA) in the bile acid pool with cholesterol supersaturation of bile is prevalent in patients with cholesterol gallstones (CGs). This study examined whether this is caused by enhanced conversion of cholic acid (CA) to DCA by intestinal bacteria. METHODS: Ten patients with CGs with DCA excess (DCA/CA pool ratio, > 1.5) and 10 patients with low DCA (ratio, < 1.0) were compared for CA and DCA kinetics, ileal absorption of 75-Se-homotaurocholic acid (75-SeHCAT), and CA-7 alpha-dehydroxylation activity of the fecal microflora; the effects of ampicillin treatment on DCA excess were studied in 7 patients. RESULTS: Patients with DCA excess and low DCA differed (P < 0.01) in the pool size of CA (mean, 5.8 vs. 34) and DCA (28 vs. 11 mumol/kg) and DCA input (8.8 vs. 3.5 mumol.kg-1.day-1. Whereas 75-SeHCAT excretion was similar, CA-7 alpha-dehydroxylation activity and levels of fecal 7 alpha-dehydroxylation bacteria were 3- fold and 1000-fold higher (P < 0.01) in patients with DCA excess, respectively. Ampicillin treatment decreased (P < 0.02) CA-7 alpha- dehydroxylation activity and DCA pool size, expanded the CA pool to normal size, and lowered cholesterol saturation of bile. CONCLUSIONS: Increased CA-7 alpha-dehydroxylation activity of the intestinal microflora may be an important factor for CG formation or growth in these patients. (Gastroenterology 1996 Dec;111(6):1611-20)     

PREVALENCE OF ENDEMIC GOITRE IN SCHOOL CHILDREN: SHIRUR (DIST. PUNE,MAHARASHTRA)

A survey for estimation of goitre in school children in the Rural Health Training Centre, Shirur area was undertaken. A total of 4664 students from 17 schools were surveyed. The goitre prevalence was found to be 59.8% with visible goitre rate of 6.2% in pre- and peri-adolescent (10–19 years) age group. Thus a highly endemic goitre focus was located in Shirur, area in Pune District (Maharashtra). This area is located on the eastern tail-end slopes of Sahyadri Hills in Balaghat ranges, situated at an altitude of 533 metres. The area is generally drought prone and receives scanty rain, with poor agricultural practices. Environmental deficiency of iodine was found to be the main cause for this high prevalence of goitre.KEY WORDS: Goitre endemic, Iodine