Juvenile polyposis in a tropical country

The clinical profile, malignant potential, and management of 17 children with juvenile polyposis (more than five juvenile polyps) were evaluated clinically and endoscopically. Colonoscopy and polypectomy were done three weekly until colonic clearance was achieved, and thereafter two yearly. All polyps were subjected to histological examination. Mean age was 7.7 years, with a male preponderance (3:1). Presentation was with rectal bleeding (94%), pallor (65%), stunted growth (53%), and oedema (47%), and the mean (SD) duration of symptoms was 33 (27) months. None had a positive family history or any congenital anomaly. Two children had six polyps up to the transverse colon; the rest had numerous polyps all over the colon. All children had juvenile polyps on histology and 10 (59%) had adenomatous changes (dysplasia). Total colectomy was done in six for intractable symptoms. Colon clearance was achieved in eight after an average 3.4 polypectomy sessions, and three were still on the polypectomy programme. In conclusion, juvenile polyposis is commonly associated with low grade dysplasia. Serial colonoscopic polypectomy is effective but colectomy is required for intractable symptoms and when clearance of the colon is not possible.     

Early amniocentesis for prenatal cytogenetic evaluation

Early amniocentesis at 11-14 weeks gestation was evaluated in 100 consecutive patients to see how this technique compares with later amniocentesis. There were no complications as a consequence of the procedure or related pregnancy losses of chromosomally normal fetuses. Samples obtained from three (3%) patients showed insufficient cell growth; two of these patients elected a repeat procedure, which yielded a normal karyotype in each case. There were five abnormal karyotypes, one of which was a culture artifact; in the latter case, repeat amniocentesis at 15 weeks yielded a normal result. Of the 95 pregnancies with normal karyotypes, 94 were progressing normally at follow-up, and one patient elected pregnancy termination because of maternal indications. It appears that early amniocentesis may be an attractive alternative to traditional amniocentesis, in that it provides results at an earlier gestational age and may avoid certain disadvantages of chorionic villus sampling.     

Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy

Radiocontrast-induced nephropathy (RCIN) is a common cause of hospital-acquired acute renal failure and is associated with a high mortality rate. RCIN is potentially preventable, because administration of the radiocontrast agent is predictable, and a high-risk population has been identified. This multicenter, prospective, randomized, double-blind, placebo-controlled trial was performed to evaluate the efficacy of intravenous atrial natriuretic peptide (anaritide, ANP 4-28) to prevent RCIN. Patients with stable chronic renal failure (serum creatinine greater than 1.8 mg/dL or serum creatinine between 1.5 and 1.8 mg/dL with estimated creatinine clearance of < or = 65 mL/min) were assigned to receive either placebo or one of three doses of anaritide (0.01 microg/kg/min, 0.05 microg/kg/min, or 0.1 microg/kg/min) for 30 minutes before and continuing for 30 minutes after radiocontrast administration. All patients were given intravenous 0.45% saline for 12 hours before the radiocontrast procedure and continuing for 12 hours after the last dose of radiocontrast. Both ionic and nonionic radiocontrast agents were administered. RCIN was defined as either an absolute increase of serum creatinine of > or = 0.5 mg/dL or a percent increase of > or = 25% over baseline. Of the 247 patients who completed the study, 50% had diabetes mellitus. There were no statistical differences in baseline serum creatinine, change in serum creatinine, or the incidence of RCIN. The incidence of RCIN was placebo, 19%; anaritide (0.01), 23%; anaritide (0.05), 23%; anaritide (0.1), 25%. Patients with diabetes mellitus had a significantly greater incidence of RCIN: placebo, 26% versus 9%; anaritide (0.01), 33% versus 13%; anaritide (0.05), 26% versus 21%; anaritide (0.1), 39% versus 8% (diabetic v nondiabetic, P < 0.002). There was no effect in the diabetic or nondiabetic groups by anaritide on the incidence of RCIN. Comparison of the highest-risk group of patients, defined as patients with diabetes mellitus and a baseline serum creatinine > or = 1.8 mg/dL, with the lowest-risk group, defined as patients without diabetes mellitus and a baseline serum creatinine of 1.8 mg/dL or less, did not show a beneficial effect of anaritide administration. In conclusion, administration of intravenous anaritide before and during a radiocontrast study did not reduce the incidence of RCIN in patients with preexisting chronic renal failure, with or without diabetes mellitus.     

The FGF14(F145S) mutation disrupts the interaction of FGF14 with voltage-gated Na+ channels and impairs neuronal excitability

Fibroblast growth factor 14 (FGF14) belongs to the intracellular FGF homologous factor subfamily of FGF proteins (iFGFs) that are not secreted and do not activate tyrosine kinase receptors. The iFGFs, however, have been shown to interact with the pore-forming (alpha) subunits of voltage-gated Na+ (Na(v)) channels. The neurological phenotypes seen in Fgf14-/- mice and the identification of an FGF14 missense mutation (FGF14(F145S)) in a Dutch family presenting with cognitive impairment and spinocerebellar ataxia suggest links between FGF14 and neuronal functioning. Here, we demonstrate that the expression of FGF14(F145S) reduces Na(v) alpha subunit expression at the axon initial segment, attenuates Na(v) channel currents, and reduces the excitability of hippocampal neurons. In addition, and in contrast with wild-type FGF14, FGF14(F145S) does not interact directly with Na(v) channel alpha subunits. Rather, FGF14(F145S) associates with wild-type FGF14 and disrupts the interaction between wild-type FGF14 and Na(v) alpha subunits, suggesting that the mutant FGF14(F145S) protein acts as a dominant negative, interfering with the interaction between wild-type FGF14 and Na(v) channel alpha subunits and altering neuronal excitability.     

Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation

B cell lymphoproliferative disorders (BLPD) developed in eight patients following bone marrow transplantation (BMT) for leukemia (five patients) or immunodeficiency (three patients). Recipients of T depleted marrow from a mismatched donor were at particularly high risk of this complication. Six of 25 (24%) recipients of mismatched T depleted bone marrow developed BLPD. In contrast, none of 47 matched T depleted transplants, one of ten (10%) who received non-depleted marrow from an unrelated donor, and only one of 424 matched non-depleted transplants were associated with BLPD. Epstein-Barr virus (EBV) specific serology and DNA hybridization studies demonstrating five to 50 copies of EBV genome/cell in involved tissues implicate this virus as an associated etiologic agent. Restriction fragment length polymorphism (RFLP) and cytogenetic analysis of involved tissue demonstrated donor origin (five of seven) or host origin (two of seven). Histologic appearance was similar to EBV-induced polymorphic B cell proliferations described following solid organ transplantation, or which occur de novo in primary immunodeficiency. Six of seven patients with adequate tissue available for study were found to have monoclonal proliferations by: in situ immunofluorescence (six of seven), and/or immunoglobulin gene rearrangement, (four of six). Cytogenetic analysis of involved tissues from four patients showed a normal karyotype, whereas two had multiple clonal chromosomal abnormalities. Seven patients died despite aggressive attempts at therapy with combinations of antiviral, immunologic, and chemotherapeutic agents.     

Activated factor XII type A predicts long‐term mortality in patients admitted with chest pain1

Summary. Background: We assessed the relation between admission levels of activated factor XII type A (XIIaA), and long‐term all‐cause and cardiac mortality and recurrent troponin T (TnT) positive cardiovascular events in a consecutive cohort of 870 patients admitted with a clinically strongly suspected acute coronary syndrome (ACS). Methods and results: After a 24‐month follow‐up period, 138 patients (15.8%) had died and 155 (17.8%) had suffered from a recurrent TnT positive (TnT > 0.05 ng mL^?1) event. XIIaA levels were significantly lower in long‐term survivors than in patients who died (22.9 (17.7–32.1) vs. 27.2 (20.0–39.7) pmol L^?1 [median, 25 and 75% percentiles], P < 0.001). The unadjusted hazard ratio for death within 2 years in patients with XIIaA in the highest quartile was 2.49 (95% confidence interval (CI), 1.52–4.06) as compared with patients with XIIaA in the lowest quartile. In a stepwise Cox regression model for death within 2 years, XIIaA added prognostic information for all‐cause mortality (HR 2.05; 95% CI, 1.21–3.47) above and beyond age, a history of heart failure, ST‐segment elevation, TnT and B‐type natriuretic peptide (BNP). In the subgroup of patients with an admission TnT ≤ 0.05 ng mL^?1, XIIaA provided independent prognostic information for all‐cause mortality (HR 3.88; 95% CI, 1.66–9.08) and for the combined endpoint of death or recurrent TnT positive event (HR 2.46; 95% CI, 1.34–4.50). Conclusion: XIIaA, a recently identified in vivo form of activated factor XII is an independent indicator of long‐term all‐cause mortality in patients admitted with chest pain, providing prognostic information above and beyond conventional risk factors.     

In vitro characteristics of white cell-reduced single-unit platelet concentrates stored in syringes

BACKGROUND: Platelet concentrates (PCs) for premature infants may be subjected to filtration, centrifugation, and various storage conditions before transfusion. STUDY DESIGN AND METHODS: As there are few data on the cumulative effect of these procedures on PCs, platelet properties (including biochemical and functional in vitro assays) were evaluated after the processing of single units of PCs through a 1-unit-capacity high-efficiency white cell (WBC)-reduction filter followed by syringe storage at either 22 or 37 degrees C for 6 hours. Two- and 5-day-old PCs, volume-reduced PCs, and prestorage WBC-reduced PCs were evaluated. RESULTS: WBC filtration consistently resulted in a 3 to 4 log10 reduction in WBCs, with less than 15-percent platelet loss. No adverse effects of platelet function or evidence of increased platelet activation as determined by the percentage of P-selectin positivity were noted. A decrease in pH associated with increased lactate production and consumption of glucose was observed following syringe storage under all conditions tested. Such changes were most pronounced, however, with volume-reduced PCs stored at 37 degrees C (pH 6.31 +/− 0.15, lactate 23.0 +/− 3.06 mmol/L). All pH levels at the end of storage were above the minimum Food and Drug Administration requirement (pH 6.0). CONCLUSION: The in vitro data suggest that single units of PCs can undergo WBC filtration followed by syringe storage for up to 6 hours and still maintain acceptable storage characteristics. The practice of maintaining volume-reduced PCs in syringes for 6 hours at 37 degrees C in isolettes during transfusion should, however, be avoided.     

Selection of platelets for refractory patients by HLA matching and prospective crossmatching

A multi-site clinical study compared platelets chosen for refractory patients by prospective platelet crossmatching using stored donor platelets and HLA-based selection. Seventy-three patients who were refractory to random-donor platelets received two plateletpheresis components, one chosen by HLA-based criteria and the other by crossmatching. Patients were carefully evaluated to exclude nonimmune factors that could adversely affect transfusion results. Each of the five study sites used a crossmatch procedure with which it had experience. Results from this study indicate the following: 1) The overall rate of successful transfusion was similar when an HLA-based method of donor selection that includes all grades of matching and mismatching was compared to a crossmatch-based method of donor selection. 2) HLA-based selection that restricts recipients to grade A and BU matches was superior to a selection method based upon crossmatching alone. Donor selection based on HLA matching (grades A or BU) was also superior to selection based on any degree of HLA mismatching (grades BX, C, or D). 3) Selection of donors based on HLA-cross-reactive groups (defined by in vitro serologic crossreactivity) was no more successful than that based on grade C and D mismatches and was no more successful than selection by crossmatching alone. 4) Lymphocytotoxic and platelet antibodies were not detected in many of the enrolled patients, even though patients demonstrating nonimmune factors were eliminated from the study. It can be concluded that HLA-compatible (grades A and BU) platelets provide optimal support for refractory patients, but that crossmatch-selected platelets are acceptable as an alternative component.     

Strengthen international academic cooperation and exchanges: prospects in the 21st century Summary of the First World Chinese Congress of Digestion

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