Acute demyelinating disorders of the central nervous system

Opinion statement  Acute demyelinating disorders of the central nervous system represent some of the most formidable management and therapeutic challenges to clinicians. These disorders include acute relapses of multiple sclerosis, neuromyelitis optica, acute disseminated encephalomyelitis, optic neuritis, and transverse myelitis. This paper summarizes clinical manifestations of these disorders, as well as treatment strategies. Currently, immunosuppression with corticosteroids for the acute events is the mainstay of treatment. Other experimental therapies, which may be effective in certain patients, are discussed.     

Analysis of the DYSF mutational spectrum in a large cohort of patients

Dysferlinopathies belong to the heterogeneous group of autosomal recessive muscular dystrophies. Mutations in the gene encoding dysferlin (DYSF) lead to distinct phenotypes, mainly Limb Girdle Muscular Dystrophy type 2B (LGMD2B) and Miyoshi myopathy (MM). Here, we analysed the mutational data from the largest cohort described to date, a cohort of 134 patients, included based on clinical suspicion of primary dysferlinopathy and/or dysferlin protein deficiency identified on muscle biopsy samples. Data were compiled from 38 patients previously screened for mutations in our laboratory (Nguyen, et al., 2005; Nguyen, et al., 2007), and 96 supplementary patients screened for DYSF mutations using genomic DHPLC analysis, and subsequent sequencing of detected variants, in a routine diagnostic setting. In 89 (66%) out of 134 patients, molecular analysis identified two disease causing mutations, confirming the diagnosis of primary Dysferlinopathy on a genetic basis. Furthermore, one mutation was identified in 30 patients, without identification of a second deleterious allele. We are currently developing complementary analysis for patients in whom only one or no disease-causing allele could be identified using the genomic screening procedure. Altogether, 64 novel mutations have been identified in this cohort, which corresponds to approximately 25% of all DYSF mutations reported to date. The mutational spectrum of this cohort significantly shows a higher proportion of nonsense mutations, but a lower proportion of deleterious missense changes as compared to previous series. (c) 2008 Wiley-Liss, Inc.     

Advanced modeling strategy for the analysis of heart valve leaflet tissue mechanics using high-order finite element method

Modeling soft tissue using the finite element method is one of the most challenging areas in the field of biomechanical engineering. To date, many models have been developed to describe heart valve leaflet tissue mechanics, which are accurate to some extent. Nevertheless, there is no comprehensive method to modeling soft tissue mechanics, This is because (1) the degree of anisotropy in the heart valve leaflet changes layer by layer due to a variety of collagen fiber densities and orientations that cannot be taken into account in the model and also (2) a constitutive material model fully describing the mechanical properties of the leaflet structure is not available in the literature. In this framework, we develop a new high-order element using p-type finite element formulation to create anisotropic material properties similar to those of the heart valve leaflet tissue in only one single element. This element also takes the nonlinearity of the leaflet tissue into consideration using a bilinear material model. This new element is composed a two-dimensional finite element in the principal directions of leaflet tissue and a p-type finite element in the direction of thickness. The proposed element is easy to implement, much more efficient than standard elements available in commercial finite element packages. This study is one step towards the modeling of soft tissue mechanics using a meshless finite element approach to be applied in real-time haptic feedback of soft-tissue models in virtual reality simulation.     

Relevance of Hepatocyte Growth Factor and Fibroblast Growth Factor on Mouse Preimplantation Embryo Development

Objective To explore the effect of hepatocyte growth factor （HGF） and fibroblast growth factor （FGF） on preimplantation embryo development of mouse.
Methods Mated mice were killed by cervical dislocation to collect two pronucleous （2 PN） zygotes from oviduct of pregnant 1 d NMRI mice and were cultured to the hatching blastocyst stage and the number of embryo in different stages was recorded under an invert microscope. The cleavage rates of formed 2 PN zygotes were compared with blastocyst and hatching blastocyst stage in drops of T6 medium with or without HGF or FGF （0 ng/ml, 10 ng/ml, 20 ng/ml, 50 ng/ml, 1 000 ng/ml）.
Results HGF and FGF enriched embryo culture media promotea the aevetopment from 2 PN stage embryos to blastocyst. Adding 20 ng/ml of FGF or HGF to the culture medium significantly increased the percentage of 2PN embryos that developed into blastocysts （P〈0.05）, but culture of embryos in drops of T6 medium with HGF （20 ng/ml） had no improvement in in-vitro hatching.
Conclusion Exogenous HGF and FGF at low concentrations promote in-vitro mouse blastocyst formation.     

Prevalence and Correlates of Hepatitis C Infection among Male Injection Drug Users in Detention,Tehran, Iran

For the benefit of planning for the future care and treatment of people infected with hepatitis C virus (HCV) and to help guide prevention and control programs, data are needed on HCV seroprevalence and associated risk factors. We conducted a cross-sectional sero-behavioral survey of injection drug users (IDU) detained for mandatory rehabilitation during a police sweep of Tehran, Iran, in early 2006. During the study period, a consecutive sample comprising 454 of 499 (91.0%) men arrested and determined to be IDU by urine test and physical examination consented to a face-to-face interview and blood collection for HCV antibody testing. Overall, HCV prevalence was 80.0% (95% confidence interval (CI) 76.2–83.6). Factors independently associated with HCV infection included history of incarceration (adjusted OR 4.35, 95% CI 1.88–10.08), age of first injection ≤25 years (OR 2.72, 95% CI 1.09–6.82), and history of tattooing (OR 2.33, 95% CI 1.05–5.17). HCV prevalence in this population of IDU upon intake to jail was extremely high and possibly approaching saturation. Findings support that incarceration is contributing to the increased spread of HCV infection in Iran and calls for urgent increased availability of HCV treatment, long-term preparation for the care of complications of chronic infection, and rapid scale-up of programs for the primary prevention of parenterally transmitted infections among drug users.     

Gastrointestinal Cancer Educational Case Series: Management of Metastatic Adenocarcinoma of Unknown Primary Origin in a Ph+ ALL Survivor

Introduction

Secondary malignancies and chronic end-organ sequelae are significant and steadily rising consequences of cancer therapy. The workup and management of a carcinoma of unknown primary must consider the patient’s clinical presentation, radiologic and pathologic findings, and comorbidities.

Case Report

We present the case of a 50-year-old female survivor of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with significant treatment-related end-organ sequelae who developed a metastatic adenocarcinoma of unknown primary 15 years following curative therapy for her ALL. The complex management issues related to the investigations and choice of therapy for this patient are reviewed.

Discussion

This case discusses key issues related to the workup and management of a carcinoma of unknown primary. In addition, it illustrates the importance of taking patient comorbidities into consideration and tailoring investigations and therapy accordingly.     

Serum Immunoglobulins in Patients with Iron Deficiency Anemia

Iron deficiency is a common cause of anemia worldwide. Documentation shows that these patients have impaired immunity and are prone to infections. The aim of this study was to confirm whether serum immunoglobulins change in adult nonpregnant females with iron deficiency anemia. Based on patients’ clinical history, CBC results, and serum ferritin, iron and total iron binding capacity, 45 healthy patients and 45 iron deficiency anemia (hypochrom microcytic) patients were entered into this case–control study. Serum IgG, IgA and IgM were measured in patient and control groups using the nephelometry method. Both of the groups were compared using suitable statistical test. Mean serum values of IgG, IgA and IgM in the patient group were 12.47 ± 7.67, 1.93 ± 0.92 and 1.35 ± 0.90 g/l respectively. Mean serum values for the control group were 12.51 ± 6.85, 2.14 ± 0.88 and 1.49 ± 0.73 g/l respectively. Although serum immunoglobulins were slightly lower in the patient group compared to the control group these differences were not significant with the t test. Our study showed serum immunoglobulin levels did not change in iron deficiency anemia.     

Should fine‐needle aspiration cytology be the first choice diagnostic modality for assessment of all nonpalpable breast lesions? The experience of a breast cancer screening center in Alexandria,Egypt

Fine‐needle aspiration cytology (FNAC) of breast masses has been replaced by ultrasound‐guided core‐needle biopsy (USG‐CNB) in many countries. However, in Egypt, breast FNAC continues to play the major role in diagnosing breast masses. In this prospective study, we evaluated the efficacy of USG‐FNACs performed at a breast cancer screening center by comparing the FNAC results with the corresponding definitive histological examination outcome. We also investigated the role that CNB can play as a complementary diagnostic tool for FNAC in selected cases. A total of 229 consecutive nonpalpable breast masses were included in this study. Each FNAC was placed into one of four categories: 3.5% nondiagnostic, 13.5% benign, 12.3% atypical/suspicious (indeterminate), and 70.7% malignant. The overall diagnostic accuracy was 98.9%, with a specificity and sensitivity of 99.3 and 96.7%, respectively. The overall positive predictive values and negative predictive values were 99.3 and 96.7%, respectively. Only 37 masses (16%) were converted to CNB, with the indeterminate cytology being the most common cause (54%) for this conversion. Two cases demonstrating the superior benefit of FNAC over CNB are illustrated. Although we started the study by reserving CNB as a first choice to assess microcalcifications without architectural distortion, we ended the study by deciding to perform combined FNAC and CNB for this type of lesions. In conclusion, aiming to maximize the preoperative diagnosis of cancer, it would be cost efficient and time saving to use FNAC as a first‐line investigation to benefit from the wealth of cytological information yielded, followed by CNB in selected cases. Diagn. Cytopathol. 2010;38:880–889. © 2010 Wiley‐Liss, Inc.