Ferritin above 100 mcg/L could rule out colon cancer, but not gastric or rectal cancer in patients with involuntary weight loss

ABSTRACT: BACKGROUND: A tenth of patients with involuntary weight loss (IWL) have gastrointestinal cancer. Ferritin is the first parameter to be modified during the process leading to iron deficiency anaemia, therefore it should be the most sensitive. The aim of this study was to assess the ability of ferritin to rule out gastrointestinal cancer in patients with involuntary weight loss. METHODS: All consecutive patients with IWL admitted in a secondary care university hospital were prospectively studied. Ferritin, haemoglobin with erythrocyte indices and serum iron were recorded for all patients. The reference standard was bidirectional endoscopy and/or 6 months follow-up. RESULTS: 290 patients were included, a quarter had cancer, of which 22 (7.6%) had gastrointestinal cancer (8 gastric cancer, 1 ileum cancer, 13 colorectal cancer). Ferritin had the best area under the curve (AUC), both for gastrointestinal cancer (0.746, CI: 0.691-0.794), and colorectal cancer (0.765, CI: 0.713-0.813), compared to the other parameters of iron deficiency. In the diagnosis of colorectal cancer, ferritin with a cut-off value of 100 mcg/L had a sensitivity of 93% (CI: 69-100%), and negative likelihood ratio of 0.13, with a negative predictive value of 99% (96-100%), while for gastrointestinal cancer, the sensitivity was lower (89%, CI: 67-95%), with a negative likelihood ratio of 0.24. There were three false negative patients, two with gastric cancer, and one with rectal cancer. CONCLUSION: In patients with involuntary weight loss, a ferritin above 100mcg/L could rule out colon cancer, but not gastric or rectal cancer.     

A triple-blinded randomized trial comparing the hemostatic effects of large-dose 10% hydroxyethyl starch 264/0.45 versus 5% albumin during major reconstructive surgery

In Canada, hydroxyethyl starch 264/0.45 (HES 264/0.45; molar weight 264 kDa, molar substitution 0.45) has largely replaced albumin as the colloidal fluid of choice for perioperative intravascular volume expansion. The maximum recommended dose of HES 264/0.45 is 28 mL/kg; however, there are no clinical data supporting this limit. In this study we compared the hemostatic effects of HES 264/0.45 versus 5% albumin in doses up to 45 mL/kg over 24 h during major reconstructive head and neck surgery. Fifty patients were randomized to receive HES 264/0.45 or 5% human albumin from the induction of anesthesia until 24 h thereafter. Both albumin and HES 264/0.45 effectively maintained physiologic variables in the perioperative and postoperative periods. The partial thromboplastin time and international normalized ratio were significantly increased in the HES 264/0.45 group compared with the albumin group after infusion of 30 mL/kg and 45 mL/kg (P < 0.05). Factor VIII activity and von Willebrand factor level were significantly reduced in the HES 264/0.45 group compared with the albumin group after infusion of 15 mL/kg, 30 mL/kg, and 45 mL/kg (P < 0.05). Significantly more subjects in the HES 264/0.45 group received allogeneic red blood cell transfusions (P < 0.02). We conclude that HES 264/0.45 infusions >30 mL/kg over 24 h impair coagulation to a greater extent than albumin, possibly leading to more allogeneic transfusions.     

Patients’ preferences for enrolment into critical-care trials

Background  

Most critically ill patients are incapable of providing informed consent for research.     

Novel monoclonal antibodies against mouse C3 interfering with complement activation: description of fine specificity and applications to various immunoassays

The role of complement proteins in various pathophysiological settings has been studied primarily using mouse models of disease. However, the specific contribution of C3-derived fragments to these biologic processes has not been addressed in a rigorous manner because of a lack of antibodies that can selectively recognize mouse C3 or any of its degradation fragments. Here we report the generation and characterization of a panel of rat monoclonal antibodies reacting with mouse C3 and its degradation products. We describe their performance in various immunological assays such as ELISA, Western blotting, flow cytometry and immunohistochemistry. Of all the antibodies generated, one selectively recognized the C3a anaphylatoxin, and all other reacted with C3c. Furthermore, two monoclonal antibodies preferentially reacted with the cleaved C3 fragments C3b/iC3b/C3c but not native C3. Except for the one recognizing C3a, all antibodies were suitable for detecting C3 deposited on cells and tissues, two effectively inhibited the hemolytic activity of mouse complement and one enhanced C3-deposition to the cell membrane. These novel monoclonal antibodies may serve as useful reagents for elucidating functions mediated by C3-derived fragments in various pathophysiological conditions.     

Olanzapine in the treatment of pervasive developmental disorders: a case series analysis

Controlling the symptoms that are characteristic of patients with pervasive developmental disorders is often challenging. We report on the safety and efficacy of olanzapine in the treatment of 7 patients with pervasive developmental disorders. The patients were all male and ranged in age from 8 to 52 years. They received olanzapine doses of 5-10 mg/d along with their various other drug regimens. Patients were monitored and evaluated for a mean duration of 17.7 (range 12-26) months while on olanzapine therapy. Very few side effects were observed during treatment. All patients showed clinically significant improvement on the Clinical Global Impressions scale, as well as an improved score as measured by the Global Assessment of Functioning scale. Our observations support the use of long-term olanzapine therapy for symptom control in patients with pervasive developmental disorders.     

Dysfunctional autogenous hemodialysis fistulas: outcomes after angioplasty--are there clinical predictors of patency?

PURPOSE: To determine the primary and secondary patency rates for fistulas treated with angioplasty, as well as clinical predictors of fistula patency after angioplasty. MATERIALS AND METHODS: The authors reviewed their institutional experience with autogenous fistulas from June 1997 to June 2002. A total of 104 men and 36 women were treated. Mean age +/- standard deviation of patient cohort was 62.4 years +/- 15.6. Patient age and sex, age of fistula at initial intervention, presence of diabetes, side and location of fistula, location of stenosis, and number of venous stenoses dilated were examined. Patency after angioplasty was estimated by using the Kaplan-Meier method, and predictors of patency were examined by using a Cox proportional hazards model. RESULTS: One hundred fifty-one dysfunctional fistulas (94 radiocephalic and 57 brachiocephalic) were treated with angioplasty initially. Clinical success rate was 98.0% (297 of 303 interventions). At 3, 6, and 12 months, respectively, primary patency rates +/- standard errors of the estimate were 73% +/- 6, 51% +/- 7, and 39% +/- 7 for brachiocephalic fistulas and 85% +/- 4, 75% +/- 5, and 62% +/- 5 for radiocephalic fistulas; secondary patency rates were 96% +/- 2.4, 89% +/- 4, and 85% +/- 5 for brachiocephalic fistulas and 91% +/- 3, 88% +/- 3, and 86% +/- 4 for radiocephalic fistulas. For all time points, there was a significant difference in primary (P =.004) but not secondary (P =.45) patency between radiocephalic and brachiocephalic fistulas. Stenosis was most prevalent within 3 cm of the arteriovenous anastomosis in 74 (64%) of the 116 dysfunctional radiocephalic fistulas and at the cephalic arch in 22 (30%) of the 74 dysfunctional brachiocephalic fistulas. The clinical variables examined did not influence outcome. Complications occurred in seven (2.3%) of 303 interventions. CONCLUSION: Patency after angioplasty in dysfunctional autogenous hemodialysis fistulas exceeds that observed in hemodialysis grafts. None of the clinical or anatomic variables examined affected patency outcome.     

Study of emulsion stabilization by graft copolymers using the optical analyzer Turbiscan

Oil-in-water nanoemulsions were prepared using a series of synthetic graft copolymers with a backbone of dextran (DEX) and a number of side chains of poly-epsilon-caprolactone (PCL). In this paper, we focus on the o/w emulsion stabilizing abilities of these novel PCL-DEX copolymers, using a recently developed optical analyzer (Turbiscan). The main advantage of Turbiscan is to detect the destabilization phenomena in non-diluted emulsion, much earlier than the naked eye's operator, especially in the case of an opaque and concentrated system. This study shows that PCL-DEX copolymers successfully stabilized ethyl acetate-in-water emulsions, even in the absence of additional surfactants, whereas they were not efficient in stabilizing methylene chloride-in-water emulsions which coalesced fast and irreversibly. The ethyl acetate-in-water emulsion stabilizing ability of PCL-DEX seemed to be related to the localization of their blocks with regard to the oil-water interface.     

Interactions between a macrophage cell line (J774A1) and surface-modified poly (D,L-lactide) nanocapsules bearing poly(ethylene glycol)

The interactions of naked and surface-modified poly(D,L-lactic acid) (PLA) nanocapsules (NC), where polyethyleneglycol (PEG) was adsorbed or covalently attached, have been studied with a macrophage-like cell line. The fluorescent oil marker, DiD, was successfully encapsulated in NCs in order to follow their interactions with cells. The cell-associated fluorescence obtained with PEG-PLA NC was about 3- to 13-fold lower than that obtained with naked-PLA NC. The effects of PEG chain length, its content as a percentage of total polymer and NC concentration in the culture medium were evaluated. PEG-PLA NC showed dramatically reduced fluorescence association with cells during an 18 h incubation compared with naked-PLA NC, showing that covalent attachment of PEG is important for the persistence of low uptake. The best results in reducing cell-associated fluorescence were obtained with a surface-modified PEG-PLA NC bearing a chain with 20000 MW. Increasing the percentage of PEG produced a reduction in marker association for a given PEG chain length. Moreover, when the PEG-containing poloxamer was simply adsorbed, marker association was dependent on the extent of dilution and the type of serum in the culture medium. Serum proteins, especially immunoglobulins, increased cell-associated fluorescence for PEG-adsorbed NC, but had very little effect on PEG-PLA NC. Marker association was only partially inhibited in the presence of cytochalasin B. The mechanisms of cell-NC interaction depended on the characteristics of the NC surface in each formulation. When the NC was physically separated from cells no diffusion of fluorescent marker in aqueous medium occurred. Nevertheless, collision-mediated transfer of DiD from NC to J774 cells was a non-negligible route of marker transfer, mainly for naked NC. However, this collision-mediated transfer was reduced for the PEG-PLA NC probably due to the restricted contact between NC and cells afforded by PEG steric hindrance at the surface.