Obliterative portal venopathy: A comparative study of 184 cases of extrahepatic portal obstruction and 469 cases of idiopathic portal hypertension

Abstract A total of 184 cases of extrahepatic portal obstruction (EHPO), mostly demonstrated by intraoperative portography and studied at 17 institutes during the period 1957–1983, were compared with 469 cases of idiopathic portal hypertension (IPH) similarly studied. Of the cases of EHPO, there were 101 males and 83 females; 93 were under 20 years of age and the average age was 25.9 years (i.e. much younger than that of IPH cases). There were two age peaks, one before age 19 years and the other at age 40–49 years. One out of three adult cases had a history of abdominal surgery, but otherwise the aetiologic factor was difficult to elicit. Bleeding was the initial symptom in the majority, and splenectomy and haematological findings of hypersplenism were less pronounced compared with IPH. Liver function tests were almost always normal. The liver appeared normal macroscopically in 69% and histologically in 35%. The changes seen in the remainder were similar to those in IPH; they were less frequent in young patients than in cases above age 20 years. Compared with IPH, the wedged hepatic venous pressure in patients with EHPO was lower and the gradient from the portal venous pressure was greater. It is concluded that extrahepatic portal obstruction is less common compared with IPH in Japan, and that there are cases particularly among adults that present clinicopathological features very similar to those of IPH. It is unclear at present whether these two disorders represent two different disease entities, or whether they represent one disorder with differences in the site of involvement along the portal vein system.     

Effects of amlodipine on transient myocardial ischaemia in patients with a severe coronary condition treated with a beta-blocker

The purpose of this trial was to study the additional anti-ischaemiceffects of amlodipine in coronary patients with ambulant ischaemiadespite beta-blocker therapy. Beta-blockers are the most effectivedrug therapy for reducing the frequency and duration of ambulatoryischaemic episodes. However, the therapeutic advantage of combinedcalcium antagonist-beta-blocker treatment remains questionable. Three hundred and thirteen patients with documented coronaryartery disease, a positive exercise test within 6 months beforeentry and background beta-blocker therapy, were screened. Inclusioncriteria (4 episodes of transient ST segment depression of 1.0 mm and/or 20 min of ischaemia) were demonstrated in a 48h ECG during the placebo run-in period in 84 (25%) of the patients.Eighty-nine percent of the ischaemic episodes were silent. Theeligible patients were then randomized in a 2-week, double-blind,parallel group study comparing placebo to amlodipune 10 mg dailyadded to the beta-blocker. The anti-ischaemic efficacy of thecombination therapy was assessed by 48 h ECG monitoring andexercise tests. Compared to placebo, amlodipine did not significantly reduceeither the frequency (3.7±4.3 vs 4±4.8 episodesin the amlodipune group) or the duration of ambulatory ischaemia(mean duration: 43.9±57.1 vs 39.6±65.7 min, totalduration 3.1±6.7 vs 2.8±6.1 h). Exercise-inducedST segment depression tended to decrease with amlodipine (58%vs 73% in the placebo group) and the ischaemia-free workloadcapacity was increased (+1.7 stage vs 0.7 stage in the placebogroup, P=0.08). These results suggest that 2 weeks treatment with amlodipinemay not provide any additional anti-ischaemic benefit in patientswith ambulant ischaemia resistant to a beta-blocker therapy.     

p27 Protein and cancers of the gastrointestinal tract and liver: an overview

GOALS: The purpose of this review is to look at the evidence presented in the literature on the immunoexpression of p27 in cancers of the gastrointestinal tract and liver. BACKGROUND: Cell cycle proteins have been shown to play an important role in the oncogenesis of many tumors. Several of these proteins have been examined in concert and in isolation, and some have been put forward as putative tumor markers. p27, which is an important inhibitory protein in the cell cycle and belonging to a group of cyclin-dependent kinase inhibitors, has also been studied in several malignancies, most notably breast, lung, bladder, and prostate cancers. Considerable work has also been done on the expression of this protein in cancers occurring within the gastrointestinal tract. RESULTS: Cancers occurring in the major sites of the gastrointestinal tract (esophagus, stomach, and colorectum) and liver show a similar pattern with regard to p27 protein levels. p27 emerges as a statistically significant predictor of survival and tumor behavior. It has been suggested that p27 loss occurs early in the carcinogenesis process, with dysplastic epithelium having decreased expression. The more aggressive, metastasizing cancers tend to lack p27 expression as well. Some studies have also invoked the subcellular localization of p27 (cytoplasmic versus nuclear) as also being of prognostic value. CONCLUSION: Therefore, in gastrointestinal and hepatic cancers, low p27 expression is regarded as an important adverse prognostic factor.     

Retroviral transduction and expression of the human alkyltransferase cDNA provides nitrosourea resistance to hematopoietic cells

Myelosuppression is the dose-limiting toxicity for nitrosourea chemotherapy. This toxicity predominantly involves modification of the O6 position of guanine with an alkyl moiety. The enzyme responsible for repair of O6-alkylguanine adducts, O6-alkylguanine-DNA alkyltransferase (alkyltransferase), is expressed at low levels in bone marrow (BM) cells. High alkyltransferase expression prevents the cytotoxicity and carcinogenicity of nitrosoureas in several transgenic and in vitro gene transfer models. We used gene transfer using a novel myeloproliferative sarcoma virus (MPSV) based retrovirus (vM5MGMT) to express the human alkyltransferase cDNA (MGMT) in human and murine hematopoietic cells. Transduced K562 cells had very high levels of alkyltransferase expression and significantly increased resistance to 1,3-bis (2- chloroethyl) nitrosourea (BCNU) as compared with untransduced K562 cells. Primary murine BM progenitors showed a high transduction efficiency with vM5MGMT and have increased BCNU resistance in vitro. After BM transplantation with vM5MGMT-transduced BM cells and BCNU treatment of these mice, BM, spleen and thymus had a 10- to 40-fold increase in alkyltransferase expression that persisted for at least 23 weeks posttransplantation. Progenitor cells procured from mice expressing high levels of alkyltransferase also had increased resistance to BCNU. Thus, an MPSV-based retroviral vector transduces mouse and human hematopoietic cells at high efficiency and results in high levels of gene expression both in vitro and in vivo. Overexpression of the alkyltransferase protein may protect hematopoietic progenitors from nitrosourea-induced myelosuppression.     

Fondaparinux combined with intermittent pneumatic compression vs. intermittent pneumatic compression alone for prevention of venous thromboembolism after abdominal surgery: a randomized, double-blind comparison

BACKGROUND: The benefit of combined mechanical and pharmacologic methods for venous thromboembolism prevention after abdominal surgery has not been clearly established. OBJECTIVES: To compare the efficacy and safety of fondaparinux in conjunction with intermittent pneumatic compression vs. intermittent pneumatic compression alone in this context. PATIENTS AND METHODS: This was a randomized, double-blind, placebo-controlled superiority trial. Patients aged at least 40 years undergoing abdominal surgery were randomized to receive either fondaparinux 2.5 mg or placebo s.c. for 5-9 days, starting 6-8 h postoperatively. All patients received intermittent pneumatic compression. The primary efficacy outcome was venous thromboembolism up to day 10. The main safety outcomes were major bleeding and all-cause mortality. Follow-up lasted 32 days. RESULTS: Of the 1309 patients randomized, 842 (64.3%) were evaluable for efficacy. The venous thromboembolism rate was 1.7% (7/424) in the fondaparinux-treated patients and 5.3% (22/418) in the placebo-treated patients (odds ratio reduction 69.8%; 95% confidence interval 27.9-87.3; P = 0.004). Fondaparinux significantly reduced the proximal deep vein thrombosis rate from 1.7% (7/417) to 0.2% (1/424; P = 0.037). Major bleeds occurred in 1.6% (10/635) and 0.2% (1/650) of fondaparinux-treated and placebo-treated patients, respectively (P = 0.006), none being fatal or involving a critical organ. By day 32, eight patients (1.3%) receiving fondaparinux and five (0.8%) receiving placebo had died. CONCLUSIONS: In patients undergoing abdominal surgery and receiving intermittent pneumatic compression, fondaparinux 2.5 mg reduced the venous thromboembolism rate by 69.8% as compared to pneumatic compression alone, with a low bleeding risk as compared to placebo.     

Nationwide HIV prevalence survey in general population in Niger

A national population-based survey was carried out in Niger in 2002 to assess HIV prevalence in the population aged 15-49 years. A two-stage cluster sampling was used and the blood specimens were collected on filter paper and tested according to an algorithm involving up to three diagnostic tests whenever appropriate. Testing was unlinked and anonymous. The refusal rate was 1.1% and 6056 blood samples were available for analysis. The adjusted prevalence of HIV was 0.87% (95% CI, 0.5-1.3%) and the 95% CI of the estimated number of infected individuals was 22 864-59 640. HIV-1 and HIV-2 represented, respectively, 95.6% and 2.9% of infections while dual infections represented 1.5%. HIV positivity rate was 1.0% in women and 0.7% in men. It was significantly higher among urban populations than among rural ones (respectively, 2.1% and 0.6%, P < 10(-6)). Using logistic regression, the variables significantly related to the risk of being tested positive for HIV were urban housing, increasing age and being either widowed or divorced. The estimate from the national survey was lower than the prevalence assessed from antenatal clinic data (2.8% in 2001). In the future, the representativeness of sentinel sites should be improved by increasing the representation of rural areas accounting for more than 80% of the population. Compared with other sub-Saharan countries, the HIV prevalence in Niger is still moderate. This situation represents a strong argument for enhancing prevention programmes and makes realistic the projects promoting an access to potent antiretroviral therapies for the majority.