Intravenous bevacizumab causes regression of choroidal neovascularization secondary to diseases other than age-related macular degeneration

PURPOSE: To investigate the safety, tolerability, and bioactivity of intravenous infusions of bevacizumab in patients with choroidal neovascularization (CNV) attributable to causes other than age-related macular degeneration. DESIGN: Nonrandomized clinical trial. METHODS: Ten patients with CNV received infusions of 5 mg/kg of bevacizumab. The primary efficacy outcome measure was change in visual acuity (VA; Early Treatment Diabetic Retinopathy Study letters read at 4 meters) at 24 weeks and secondary measures were changes from baseline in excess foveal thickness (center subfield thickness), area of fluorescein leakage, and area of CNV. RESULTS: Infusions were well tolerated and there were no ocular or systemic adverse events. At baseline, median VA was 25.5 letters read at 4 meters (20/80) and median foveal thickness was 346 mum. At the primary endpoint (24 weeks), median VA was 48.5 letters (20/32), representing four lines of improvement from baseline (P = .005), median foveal thickness was 248 mum representing a 72% reduction in excess foveal thickness (P = .007). Four of nine patients had complete elimination of fluorescein leakage, three had near complete elimination (reductions of 91%, 88%, and 87%), two had modest reductions, and one had no reduction. All patients except one showed a reduction in area of CNV with a median reduction of 43%. CONCLUSIONS: Despite the small number of patients studied, the marked improvement in VA accompanied by prominent reductions in foveal thickness, fluorescein leakage, and area of CNV suggest a beneficial effect. It may be worthwhile to consider further evaluation of systemic bevacizumab in young patients with CNV.     

Evaluation of diluted amniotic fluid effects on histological changes of intestine of rabbit fetus with gastroschisis

Amniotic fluid exchange is a method for prevention of intestinal damage in gastroschisis, but its techniques are different in studies. We investigated the effects of amnioinfusion exchange on histological changes of intestine and feasibility and safety of amniotic fluid exchange through central vein catheter (CVC) placed in pregnant rabbit uterus. A total of 15 pregnant New Zealand white rabbits were selected. Fetuses were randomly divided into three groups (case, control, sham). On gestational day 25, under general anesthesia with midline laparotomy, the graved bicornuate uterus was exposed. In controls, fetus abdomen was opened by a transverse incision in right lower quadrant region and intestines were eviscerated. In cases, after intestine evisceration, a central venous catheter was passed from mother skin and uterus and fixed to uterus wall. In shams, fetus was delivered on gestational day 32 and its abdomen was opened. In case group, after operation, 1–2 cc of warm saline solution was replaced through catheter every 6 h. On gestational day 32, fetuses of case and control groups were delivered. Mucosal and serosal thickness, muscle thickness, fibrin deposition, serosal collagen and ganglia were compared. Ten fetuses as shams, 7 fetuses as controls and 7 fetuses as case group were studied. Serosal thickness was 4.5 ± 3.6 μm in shams, 64.2 ± 28.7 μm in controls and 6 ± 4.1 μm in cases. Serosal thickness in control group was higher than sham (P < 0.001) and case (P < 0.002) groups. In case group, infiltration of inflammatory cells with mild edema without fibroblast infiltration was seen. Application of the CVC technique was found to be a simple procedure that effectively decreased serosal inflammatory response of intestine in gastroschisis.     

BRAF mutations are associated with increased iron regulatory protein‐2 expression in colorectal tumorigenesis

A role for iron in carcinogenesis is supported by evidence that iron metabolism proteins are modulated in cancer progression. To date, however, the expression of iron regulatory protein‐2 (IRP2), which is known to regulate several iron metabolism proteins, has not been assessed in colorectal cancer. Expression of IRP2 was assessed by quantitative RT‐PCR and immunohistochemistry in human colorectal cancer tissue. By interrogating The Cancer Genome Atlas (TCGA) database, expression of IRP2 and transferrin receptor‐1 (TfR1) was assessed relative to common mutations that are known to occur in cancer. The impact of suppressing IRP2 on cellular iron metabolism was also determined by using siRNA and by using the MEK inhibitor trametinib. IRP2 was overexpressed in colorectal cancer compared to normal colonic mucosa and its expression was positively correlated with TfR1 expression. In addition, IRP2 expression was associated with mutations in BRAF. The MEK inhibitor trametinib suppressed IRP2 and this was associated with a suppression in TfR1 and the labile iron pool (LIP). Moreover, epidermal growth factor stimulation resulted in decreased ferritin expression and an increase in the LIP which were independent of IRP2. Results presented here suggest that ablating IRP2 provides a therapeutic platform for intervening in colorectal tumorigenesis.     

Changing epidemiology of AA amyloidosis: clinical observations over 25 years at a single national referral centre

Objective: Systemic AA amyloidosis is a serious complication of chronic inflammation; however, there are relatively few published data on its incidence. We investigated the changing epidemiology of AA amyloidosis over a 25-year period at a single national referral centre.

Methods: We conducted a retrospective study of all patients diagnosed with AA amyloidosis who had attended the centre between 1990 and 2014 inclusive. Six hundred and twenty-five patients were studied in three cohorts: C1: 1990–1997; C2: 1998–2006; C3: 2007–2014.

Results: Mean age at presentation increased from 46 in C1 to 56 in C3 (p?p?=?.0006). Comparison of underlying diseases between C1 and C3 revealed a reduction in patients with juvenile idiopathic arthritis from 25% to 2% (p?p?p?<.0001). More patients were in end-stage renal failure at presentation in C3 (29%) than C1 (15%) (p?=?.0028). Median age at death was later in C3 (62 years) than C1 (54 years) (p?=?.0012).

Conclusion: These data suggest both falling incidence and better outcome in AA amyloidosis over a quarter of a century, reflecting advances in therapeutics and overall management of complex chronic disease in an ageing population. AA amyloidosis of uncertain aetiology presents an emerging major problem. Newer techniques such as next-generation sequencing may aid diagnosis and effective treatment, thereby improving overall survival.     

Components and determinants of therapeutic delay in patients with acute ST-elevation myocardial infarction: A tertiary care hospital-based study

Background

Delayed reperfusion is associated with worse outcomes in ST-segment elevation myocardial infarction (STEMI). This study was conducted to assess the components and determinants of therapeutic delay in STEMI patients of our state.