Sensitive and accurate identification of PNH clones based on ICCS/ESCCA PNH Consensus Guidelines—A summary

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic stem cell disorder resulting from the somatic mutation of the X‐linked phosphatidyl‐inositol glycan complementation Class A (PIG‐A) gene. Depending on the severity of the mutation in the PIG‐A gene, there is a partial or absolute inability to make glycosylphosphatidyl‐inositol (GPI)‐anchored proteins including complement‐defense structures such as CD55 and CD59 on RBCs and WBCs. Flow cytometric detection of PNH clones has become the gold standard and has played an increasingly important role in the diagnosis, monitoring, and clinical management of patients with PNH. Recently, a 4‐part set of Consensus Guidelines have been published by flow experts in the field to address the key assay‐specific considerations for the identification of PNH clones in RBC and WBC, how to report such data and a full validation document for the assays described. Below, we have summarized the most significant aspects of this International effort.     

Immunocytochemical detection of carcinoembryonic antigen in fine-needle aspirates from patients with diverse breast diseases

Fine-needle aspirates and paraffin-embedded tissue sections from 91 cases with diverse breast diseases were immunostained with carcinoembryonic antigen (CEA) monoclonal antibody using a BioGenex StrAviGen kit based on the biotin-streptavidin amplified methodology. The results were compared with histopathologic tumor type and tumor stage. CEA was not expressed in fibrocystic changes with mild or florid epithelial hyperplasia (n = 23) and fibroadenomas (n = 8). On the other hand, 90% (56/60) of primary breast carcinomas showed positive cytoplasmic staining for CEA. No correlation was found between CEA expression, histopathologic tumor type, and tumor stage. We suggest that CEA immunocytochemistry will help in the accurate diagnosis of primary breast carcinoma in fine-needle aspirates in addition to the usual cytological criteria.     

Analysis of bipolar disorder using affected relatives

We have analyzed the GAW10 data from several studies of bipolar affective disorder (BPAD) using the software packages SimIBD and SIMWALK2. SimIBD implements a simulation-based affected-pedigree-member (APM) statistic, called SimAPM, as well as an APM-like statistic, also called SimIBD, that measures identical-by-descent (IBD) sharing. SIMWALK2 uses Markov chain Monte Carlo techniques to compute several IBD-based statistics on the degree of marker-allele clustering among all affected relatives. We have found no strong evidence of linkage to either chromosome 5 or 18. However, we did find that several markers showed p-values less than 0.01 and may deserve further study. © 1997 Wiley-Liss, Inc.     

Neuronavigated surgery of intracranial cavernomas--enthusiasm for high technologies or a gold standard?

AIM: The aim of this study was to investigate the effect of neuronavigation on the following parameters: "skin incision", "craniotomy", "intraoperative anatomical orientation", "dissection guiding", "localization of the pathological formation", "assessment of the degree of resection" and "duration of surgical procedure" in resections of intracranial cavernomas and to specify the indications for neuronavigation in their surgical treatment. PATIENTS AND METHODS: The present prospective study included 20 patients with intracranial cavernomas who underwent neuronavigated surgery between March 2003 and December 2005 at the Clinic of Neurosurgery of the "St. I. Rilsky" University Hospital, Medical University, Sofia. The female/male ratio in the series was 9/11 (45%-55%). The patients' mean age was 27.96 +/- 11.61 years (age range 1.2 to 44 years). The patients were examined and followed up in a standard manner. RESULTS: Cavernous malformations were totally removed in 19 patients. One patient with thalamic cavernoma underwent navigated endoscopic biopsy. There was no morbidity or mortality associated with the method. Neuronavigation allowed precise localization and individual design of the skin incision and craniotomy. Neuronavigated intraoperative anatomical orientation, dissection guiding, localization of the pathological formation, and assessment of degree of resection were evaluated as markedly useful. They resulted in excellent surgery results and reduced operation time in comparison with the conventional surgery. CONCLUSION: In intracranial cavernomas frameless stereotaxy provides the surgeon with useful feedback in the preoperative anatomical orientation, the planning and simulation of surgical approach, the intraoperative navigation, in avoiding vital neurovascular structures, in the assessment of the degree of resection and the identification of possible residual parts. That is why cavernous malformations are among the most common indications for cranial neuronavigation.     

Predictors of the intima‐media thickness of carotid artery in asymptomatic newly detected severe hypercholesterolemic patients

Background: Data about predictors of intima‐media thickness (IMT) of common carotid artery (CCA) in asymptomatic subjects with newly detected severe hypercholesterolemia is scarce. Aim: This research is aimed at studying the predictors of the IMT of CCA among basic atherogenic risk biomarkers – lipid [total cholesterol (TC), triglycerides, high‐density lipoprotein cholesterol, low‐density lipoprotein (LDL) cholesterol, Apolipoprotein‐B, Apolipoprotein‐Ai, Apolipoprotein‐B/A₁ index] and non‐lipid, [asymmetric dimethylarginine (ADMA), total homocysteine, cell adhesion molecules] in asymptomatic subjects with newly detected severe hypercholesterolemia. Methods: Two hundred and fifty asymptomatic patients with severe, newly hypercholesterolemia and 200 controls were evaluated. Hypercholesterolemia was defined as TC > 7·5 mm and LDL cholesterol > 4·9 mm . The ADMA and cell adhesion molecules were determined by ELISA and total homocysteine by high‐performance liquid chromatography. Results: There was significant difference between the two groups in respect to all lipid biomarkers (P<0·001). Hypercholesterolemic patients had significantly higher level of ADMA, sVCAM‐1, sICAM‐1, IMT (P<0·001), whereas no significant difference was found between two groups with respect to total homocysteine, P‐selectin and E‐selectin (P>0·05). A strong positive correlation between IMT mean and age (r_xy = 0·714; P<0·001), Apolipoprotein‐B (r_xy = 0·706; r_xy < 0·001), Apolipoprotein‐B/A₁ (r_xy = 0·324; P<0·001), ADMA (r_xy = 0·603; P<0·001) was found. The subsequent linear and multiple regression analysis selected age and Apolipoprotein‐B as most significant factors in relation to IMT mean. Apolipoprotein‐B is a better factor for assessment of risk, as LDL cholesterol underestimates the risk in asymptomatic subjects with newly detected severe hypercholesterolemia, until more rapid and feasible methods for measurement of small and dense LDL are available.     

Prebypass histological and ultrastructural evaluation of the long saphenous vein as a predictor of early graft failure

BACKGROUND: Twenty percent of the long saphenous vein (LSV) grafts that are employed as coronary bypass conduits occlude during the first year after the operation. The aim of this study was to evaluate the morphological parameters of the LSV grafts before implantation as predictors for the early occlusion of the grafts. METHODS: Forty-two samples of LSV grafts were examined via light, transmission electron, and scanning electron microscopy and evaluated clinically and by angiography at 6 months and 2 years after the operation. Morphological parameters were statistically analyzed and examined for their significance on the viability of the vein grafts. RESULTS: Six (14.28%) of the examined grafts occluded within the first 6 months after the operation, and 11 grafts (26.19%) occluded within the first 2 years. The grafts that occluded at 6 months were characterized by thick intima (mean value, 206+/-32.29 vs. 67.44+/-10.17 in the group functioning normally and 98.42+/-34 in the group occluded within 2 years), low endothelial coverage (22.7+/-4.04 vs. 64.61+/-2.89 and 26.06+/-1.78 in the corresponding groups), and narrow lumen (46.73+/-9.69 vs. 527.18+/-45.78 and 204.26+/-16.5 in the corresponding groups). The presence of foam cells, edema, calcification, neovascularization, and thrombus in the lumen of the veins is frequently observed in the wall of the occluded vein grafts, whereas fibrosis does not seem to be related. CONCLUSIONS: LSV grafts with low endothelial cell coverage, stenosis of the lumen, and thick walls are at an increased risk of developing intrawall lesions that lead to early graft failure.