Preservation of Bile Ductules Mitigates Bile Duct Loss

The finer branches of the biliary tree (FBBT) contain a regenerative compartment. We hypothesized that preservation of the FBBT together with its microvasculature will lead to recovery of biliary damage and prolonged preservation of bile ductules during the development of chronic liver allograft rejection. The interlobular bile ducts, portal bile ductules and extraportal biliary cells with and without microvessels were studied in sequential biopsies in five patients who fulfilled the Banff criteria of early chronic rejection (CR) (imminence group). Biopsies of CR patients (n = 12) served as controls. Biopsies were double immunostained with CD34 (microvessels) and cytokeratin 7 (biliary structures). Proliferation and proangiogenic activity were assessed with Ki67 and VEGF-A immunostaining. Severe damage of bile ducts in the imminence group did not progress to significant bile duct loss. This was associated with a high proliferative activity in all biliary structures and preservation of the microvascular compartment. VEGF-A expression was increased in all but the reperfusion biopsies. In conclusion, both regenerative activity of the FBBT and an intact microvascular compartment are associated with less damage of the biliary tree and could therefore be prerequisites for biliary regeneration.     

The influence of different error estimates in the detection of post-operative cognitive dysfunction using reliable change indices with correction for practice effects.

The reliable change index (RCI) expresses change relative to its associated error, and is useful in the identification of post-operative cognitive dysfunction (POCD). This paper examines four common RCIs that each account for error in different ways. Three rules incorporate a constant correction for practice effects and are contrasted with the standard RCI that had no correction for practice. These rules are applied to 160 patients undergoing coronary artery bypass graft (CABG) surgery who completed neuropsychological assessments preoperatively and 1 week post-operatively using error and reliability data from a comparable healthy non-surgical control group. The rules all identify POCD in a similar proportion of patients, but the use of the within subject standard deviation, expressing the effects of random error, as an error estimate is a theoretically appropriate denominator when a constant error correction, removing the effects of systematic error, is deducted from the numerator in a RCI.     

A clinical approach to the management of a patient with suspected renovascular disease who presents with leg ischemia.

Atherosclerotic renal artery stenosis (ARAS) may cause hypertension, progressive renal failure, and recurrent pulmonary edema. It typically occurs in high risk patients with coexistent vascular disease elsewhere. Most patients with ARAS are likely to die from coronary heart disease or stroke before end-stage renal failure occurs. Recent controlled trials have shown that most patients undergoing angioplasty to treat renovascular hypertension still need antihypertensive agents 6 or 12 months after the procedure. Nevertheless, the number of antihypertensive agents required to control blood pressure adequately is lower following angioplasty than for medication alone. Trials assessing the value of revascularization for preserving renal function or preventing clinical events are only in the early recruitment phase. Revascularization should be undertaken in patients with ARAS and resistant hypertension or heart failure, and probably in those with rapidly deteriorating renal function or with an increase in plasma creatinine levels during angiotensin-converting enzyme inhibition. With or without revascularization, medical therapy using antihypertensive, hypolipidemic and antiplatelet agents is necessary in almost all cases.     

IFN-alpha1,8 inhibits tumor-induced angiogenesis in murine angiosarcomas.

Interferon-alpha (IFN-alpha) has proved effective in the treatment of hemangiomas, hemangioblastomas, and Kaposi's sarcoma. To investigate the ability of IFNs to inhibit angiosarcoma, we used two transformed murine endothelial cell lines that form angiosarcomas in vivo. SVR and MS1-VEGF cell lines express oncogenic H-ras or vascular endothelial growth factor (VEGF), respectively. IFN-alpha1,8, which is active against murine and human cells, inhibited SVR and MS1-VEGF proliferation in vitro by 40% at 10(3) U/mL (p = 0.028). In vivo, IFN-alpha1,8 inhibited SVR tumor volume by 71% (p = 0.047) and MS1-VEGF volume by 79% (p = 0.003). Tumor-induced angiogenesis was decreased in SVR tumors by 52% (p = 0.005) and in MS1-VEGF tumors by 58% (p = 0.001). Sera from IFN-alpha1,8-treated mice bearing either SVR or MS1-VEGF tumors demonstrated a 5-fold increase in IP-10/CXCL10 (p = 0.001), an IFN-induced antiangiogenic protein. Both recombinant IP-10 and IFN-alpha1,8 inhibited human umbilical vein endothelial cell (HUVEC) vessel formation in the fibrin gel assay, a three-dimensional culture model of angiogenesis, by 56% at 25 ng/mL and 50% at 1.2 ng/mL, respectively (p < 0.001). An IP-10 blocking antibody restored vessel formation to 80% of untreated controls (p = 0.001). Given the magnitude of the in vivo response, these data suggested that the antitumor effects of IFN-alpha1,8 were likely mediated through angiogenesis inhibition rather than solely by direct inhibition of tumor cell proliferation.     

Treatment of dysfunctional uterine bleeding in the perimenopause: the effects of adding combined estradiol/norethisterone acetate therapy to goserelin acetate treatment--a randomized, placebo-controlled, double-blind trial.

OBJECTIVE: To assess the effects of adding combined estradiol/norethisterone acetate therapy (CENT) to goserelin acetate treatment (GA) of dysfunctional uterine bleeding (DUB) in perimenopausal women. METHODS: In a randomized, placebo-controlled, double-blind trial followed by an open follow-up study, 31 perimenopausal women with DUB were recruited from gynecological outpatient departments of two Dutch hospitals and randomized for treatment with either GA/placebo or GA/CENT for 6 months followed by 18 months of GA/CENT for all. The main outcome measures were abdominal pain, number of bleeding days, double-layer endometrial thickness (DET), Greene climacteric score (GCS), visual analog scale for well-being, bone mineral density (BMD) and mammographic density (BI-RAD score). RESULTS: Abdominal pain, number of bleeding days and DET decreased in both groups, the between-group difference in decrease not being statistically significant. GCS initially showed significant improvement in the GA/CENT group. BMD decreased significantly in the GA/placebo group (-4.1%) compared with the GA/CENT group (-0.3%). Another 18 months of GA/CENT did not result in a lasting difference in BMD between groups. BI-RAD scores did not differ significantly between or within the two groups. CONCLUSIONS: Adding CENT to GA treatment for DUB in perimenopausal women initially prevented BMD loss and improved climacteric complaints, while having no negative impact on vaginal bleeding, abdominal pain or BI-RAD scores. However, prolonged treatment did not result in a lasting prevention of bone loss.     

The Impact of Parity on Course of Labor in a Contemporary Population

Abstract: Background: Few studies have examined in depth the labor progression of multiparas to determine if there is any additional impact of being parous beyond the first birth. The objective of this study was to determine the effect of parity on labor progression in contemporary obstetric practice. Methods: Our sample consisted of all low‐risk women who delivered a term, live‐born infant from January 2002 to March 2004 at a single institution in Delaware, United States (n = 5,589). The median duration of labor by each centimeter of cervical dilation was computed for parity = 0 (n = 2,645); parity = 1 (n = 1,839); parity = 2 (n = 750); and parity = 3 + (n = 355). Results: Multiparas had a significantly faster labor progression from 4 to 10 cm (293, 300, and 313 min, respectively, for parity = 1, parity = 2, and parity = 3 +), compared with nulliparas (383 min for parity = 0), as well as a shorter second stage of labor. However, no significant differences were found in duration of the active phase or the second stage of labor among multiparas. Conclusions: Additional childbearing appears to have no effect of on the progression of labor among multiparous subgroups. The difference in duration of the active phase between nulliparas and multiparas is substantially smaller in a contemporary population. (BIRTH 33:1 March 2006)     

Pseudotumour cerebri in a young obese woman on oral contraceptives.

OBJECTIVES: Pseudotumour cerebri has been previously recognized as a neurological side effect of combined oral contraceptives but has not been diagnosed with a delay of 3 years after initiation of combined oral contraceptives. CASE REPORT: A 19-year-old obese woman developed visual impairment and headache, 4 months after starting combined oral contraceptives. Three years later symptoms deteriorated and she presented with prominent tendon-jerks and congested optical-discs. Normal CSF drained with high pressure from the spinal tap. Pseudotumour cerebri was diagnosed. Headache and visual impairment resolved within 3 weeks after discontinuation of combined oral contraceptives. CONCLUSIONS: Combined oral contraceptives-induced pseudotumour cerebri may remain undetected for years. Young, obese women with visual impairment and headache under combined oral contraceptives should undergo immediate neurological and ophthalmological investigation.