Endoscopic management of acute calculous cholangitis

Acute cholangitis is associated with significant morbidity and mortality. Endoscopic drainage procedures have been shown to be a safe and effective mode of treatment in acute cholangitis. As there is paucity of large series on endoscopic management of acute cholangitis, a study was performed to evaluate safety and efficiency of endoscopic biliary decompression in acute cholangitis. The study included 89 consecutive patients (mean age 55 ± 15 years; range 35–70 years; 50 males) with acute cholangitis requiring biliary drainage. Main presenting features were upper abdominal pain (84%), fever with chills (90%) and jaundice (74%). Altered sensorium, hypotension, features of peritonitis and acute renal failure were present in 15, 11, 18 and 5%, respectively. Endoscopic procedures performed were endoscopic sphincterotomy (ES) with stone extraction (n= 40); ES with endoscopic nasobiliary drainage (ENBD; n= 30); ENBD without ES (n= 8); and ES with stent placement (n= 11). Of the 89 patients, 85 (95%) responded within 48–72 h. Endoscopic common duct clearance could be achieved in 58 of 78 (74%) patients, whereas in 11 patients undergoing stent placement, stone extraction was not attempted. Complications included post-sphincterotomy bleed (n= 2), retroduodenal perforation (n= 1) and acute pancreatitis (n= 1) with an overall complication rate of 4.4%. All the complications were seen in patients undergoing ES with stone extraction. Mortality was 3.3%. In conclusion, endoscopic biliary drainage is a safe and effective mode of treatment for acute cholangitis. Endoscopic nasobiliary drainage or stent placement is safer than ES in acute cholangitis as an initial step.     

An immunocytochemical study of the distribution of proline-4- hydroxylase in normal, osteoarthritic and rheumatoid arthritic synovium at both the light and electron microscopic level

The monoclonal antibody 5B5 reacts with the beta subunit of proline-4- hydroxylase, the enzyme which catalyses the formation of 4-hydroxyl proline in collagen and other proteins with collagen-like amino acid sequences. This study aims to assess the production and tissue distribution of this enzyme in normal and diseased synovia from patients with various joint diseases, on the basis that it is a putative marker of collagen-producing cells and, therefore, in this context, of fibroblasts. Sections from five normal, 10 osteoarthritic (OA) and 26 rheumatoid arthritic (RA) synovia were labelled with a mouse monoclonal antibody to proline-4-hydroxylase. The enzyme was found to be expressed by a proportion of synovial intimal cells and by fibroblasts in the underlying connective tissue in normal, OA and RA synovia. Labelling was more pronounced in OA and RA cases. The intimal cells labelling positively showed type B synoviocyte morphology, which was confirmed by subsequent double immunolabelling with 5B5 and antibody against type IV collagen using immunocytochemistry and immunoelectron microscopy.      

Impaired right ventricular systolic function demonstrated by reduced atrioventricular plane displacement in adults with Marfan syndrome

AIMS: The right ventricle (RV) ejects the same volume of blood at the same rate as the left ventricle (LV). Mild LV dysfunction has been demonstrated in Marfan syndrome (MFS). However, little attention has been paid to the functioning of the RV. The aim of this study was to assess RV function in unoperated adult MFS patients. METHODS AND RESULTS: In 66 unoperated (15-58 years) MFS patients and 61 controls, rate of pressure rise (dp/dt) in RV, and tricuspid annular motion (TAM) were studied using conventional echocardiography and tissue Doppler imaging (TDI). When compared with controls, MFS patients showed impaired RV systolic function as expressed by a reduced dp/dt, TAM obtained by M-mode echocardiography, and peak TDI systolic velocities at the basal lateral wall (745.36+/-37.85 vs. 1103.30+/-27.30 mmHg, P<0.001; 2.2+/-0.05 vs. 2.5+/-0.05 cm, P<0.001; and 0.13+/-0.002 vs. 0.16+/-0.002 m/s, P<0.001, respectively). CONCLUSION: This study demonstrated a primary impairment of RV systolic function in MFS. This is the first study to report RV dysfunction in MFS. Such data could prove valuable during the peri-operative and long-term medical management of MFS patients.     

Epidemiologic characteristics of blood donors with antibody to human immunodeficiency virus

From March 1985 through July 1986, blood donors who were positive for antibody to human immunodeficiency virus (HIV) were evaluated at three major blood centers in the United States. Of 818,629 donations, 450 (0.05%) were HIV antibody-positive. The seroprevalence decreased from 0.07 to 0.04 percent during the study period, due perhaps to a decline in repeat donors. HIV-seropositive donors tended to be 20 to 29 years old (52%) and male (88%). HIV seroprevalence among white donors (2/10,000 donations) was less than that among Hispanic (9/10,000; p less than 0.0001) and black donors (31/10,000; p less than 0.0001). Of 152 seropositive men interviewed, 77 percent reported sexual contact with men; of this latter group, 53 percent were bisexual. Fifteen (44%) of 34 seropositive women had apparently acquired infection from heterosexual contact, and an equal number denied having any known risk factors for HIV infection. Educational efforts must address women and bisexual men who do not perceive themselves to be at risk for HIV infection and should be specifically designed for the mores of different racial and ethnic groups.     

Molecular analysis of clonality and bcr rearrangements in Philadelphia chromosome-positive acute lymphoblastic leukemia

Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) patients consistently show a rearrangement in a 5.8-kilobase length of chromosome 22, referred to as the breakpoint cluster region (bcr). In Ph1-positive acute lymphoblastic leukemia (ALL), the breakpoint in chromosome 22 is more heterogeneous and, in some instances, does not occur within this region. In such cases the cell of origin of the neoplastic clone and the relationship of the disease to CML has remained obscure. We have analyzed the bcr rearrangement in the malignant cells from three patients who presented with Ph1-positive ALL and who in cytogenetic studies had shown evidence of variable involvement of myeloid cells in the Ph1-positive clone. Rearrangements in bcr typical of most cases of CML were detected in purified granulocyte preparations from two of the ALL patients (nos. 1 and 2) and in the blasts from patient 3 at the time of her terminal relapse. In the same analysis the simultaneously obtained granulocytes from patient 3, however, did not show any evidence of bcr rearrangement. Patient 3 was also heterozygous for the BamHI polymorphism in the X- linked hypoxanthine phosphoribosyltransferase (HPRT) gene, thus permitting a different method of clonal analysis based on methylation differences in active and inactive alleles. When DNA from her granulocytes that had shown no bcr rearrangement was hybridized to an HPRT probe, a pattern typical of a polyclonal population was seen. A similar pattern was exhibited by her marrow fibroblasts. In marked contrast, her simultaneously isolated blasts showed an unambiguous monoclonal pattern. These findings demonstrate the origin of the disease in the first two patients in a cell with myelopoietic as well as lymphopoietic potential and confirm the restricted lymphoid cell origin of the neoplastic clone in the third Ph1-positive ALL patient. Furthermore, they indicate that different target cells for transformation within the hematopoietic system may be affected by very similar bcr rearrangements.     

Endoscopic management of postoperative bile leak

Significant bile leak is an uncommon but serious complication of biliary tract surgery. Of twenty-five patients presenting with postoperative bile leak, 11 had complete tie-off of common bile duct and required surgery, while the remaining 14 had injury without complete obstruction and could be managed by endoscopic methods. Of these 14 cases, bile leak occurred from the cystic duct in 11 patients and from the common hepatic duct, right hepatic duct and left hepatic duct in one patient each. Endoscopic procedures performed included sphincterotomy alone (four patients), sphincterotomy and stent placement (seven patients) and sphincterotomy followed by nasobiliary catheter drainage (three patients). There was no technical failure and bile leak was stopped in all patients. One patient died of haemobilia 5 days after stent placement. When technically feasible, postoperative bile leak can be managed safely and effectively by endoscopic methods, obviating the need for surgical reexploration.     

Randomized comparison of busulfan and hydroxyurea in chronic myelogenous leukemia: prolongation of survival by hydroxyurea. The German CML Study Group

In a randomized multicenter study the influence of hydroxyurea versus busulfan on the duration of the chronic phase and on survival of chronic myelogenous leukemia (CML) was determined. In addition cross resistance and adverse reactions of the drugs were analyzed. From July 1983 to January 1991, 441 CML patients were randomized to receive hydroxyurea or busulfan. Of these, 90.7% were Philadelphia positive; 25.7% were low, 38.2% intermediate, and 36.2% high risk patients according to Sokal's score. The median survival of the busulfan treated Philadelphia-positive patients is 45.4 months and of the hydroxyurea group 58.2 months (P = .008). The survival advantage for the hydroxyurea treated patients is recognized in all risk groups. Sixty four patients reached therapy resistance before blast crisis and were crossed over to the alternative drug. The 23 patients with primary hydroxyurea had a median survival of 5.6 years, the 41 patients with primary busulfan therapy a median survival of 2.7 years (P = .02). Adverse reactions were less frequent with hydroxyurea with no severe adverse effects (lung fibrosis, long lasting bone marrow aplasia). The analysis of white blood cell counts in the course of treatment showed lower counts in the hydroxyurea patients. We conclude that hydroxyurea is superior to busulfan in therapy of CML in chronic phase and should be used as first line therapy. Busulfan may have a role as secondary therapy after hydroxyurea resistance or intolerance.     

SIRT1 as a potential biomarker of response to treatment with glatiramer acetate in multiple sclerosis

SIRT1, a NAD dependent histone and protein deacetylase, is a member of the histone deacetylase class III family. We previously showed that SIRT1 mRNA expression is significantly lower in peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients during relapses than in stable patients. We have now investigated SIRT1 as a possible biomarker to predict relapse as well as responsiveness to glatiramer acetate (GA) treatment in relapsing-remitting MS (RRMS) patients. Over the course of 2 years, a cohort of 15 GA-treated RRMS patients were clinically monitored using the Expanded Disability Status Scale and assessed for MS relapses. Blood samples collected from MS patients were analyzed for levels of SIRT1 and histone H3 lysine 9 (H3K9) acetylation and dimethylation. During relapses, MS patients had a lower expression of SIRT1 mRNA than did stable MS patients. In addition, there was a significant decrease in H3K9 dimethylation (H3K9me2) during relapses in MS patients when compared to stable patients (p = 0.01). Responders to GA treatment had significantly higher SIRT1 mRNA (p = 0.01) and H3K9me2 levels than did non-responders (p = 0.018). Receiver operating characteristic analysis was used to assess the predictive power of SIRT1 and H3K9me2 as putative biomarkers: for SIRT1 mRNA, the predictive value for responsiveness to GA treatment was 70% (p = 0.04) and for H3K9me2 was 71% (p = 0.03). Our data suggest that SIRT1 and H3K9me2 could serve as potential biomarkers for evaluating patients' responsiveness to GA therapy in order to help guide treatment decisions in MS.     

A rapid assay for evaluation of iron-chelating agents in rats

The animal assay of potential new iron-chelating agents is at present dependent on cumbersome and imprecise iron balance studies in hypertransfused rodents. We report the development of a radioisotope assay in intact rats based on the transient labeling by ferritin 59Fe of the main source of chelatable iron within hepatocytes. The isotope was maximally available to chelators during the first 6 hr after its injection, nearly all the excretion being in the bile. The bile 59Fe/total iron ratio was independent of both the chelator and its dose. However, in iron-loaded rats, the ratio was reduced, and the isotope excretion was a less sensitive measure of intrahepatic chelation. In the proposed assay, test chelators were given to normal rats 2 hr after an intravenous injection of 59Fe-ferritin. Four hours later, the radioiron in the liver and in the gut gave a sensitive measure of the mobilization of hepatic iron to the bile. In addition, chemical iron determinations identified a small alternative source of urinary chelate with agents known to promote urine excretion in man. The assay gave a rapid and precise screen for chelators given by parenteral and oral routes.