Plasma homocysteine level and functional outcome of patients with ischemic stroke

OBJECTIVE: To investigate the possible relationships between total plasma homocysteine level (tHcy) and functional outcome of stroke patients as evaluated by the FIM instrument. DESIGN: Retrospective chart analysis. SETTING: Inpatient stroke rehabilitation ward of a university-affiliated referral hospital. PARTICIPANTS: Consecutive patients (N=113) presenting with acute ischemic stroke. Patients were divided into 2 groups according to their tHcy levels (< or = 15 micromol/L, >15 micromol/L) and into 3 groups according to their FIM scores (low, < or =40; moderate, 41-80; high, >80). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The tHcy level was determined shortly after stroke onset by a high performance liquid chromatography method with fluorescence detection. Functional outcome was measured by the FIM instrument at admission and discharge. The tHcy level and FIM scores were obtained for all patients. Data outcomes were analyzed by t tests, 1-way analysis of variance, Mann-Whitney U, and Fisher exact tests, as well as by the 2 ordered polytomous logistic regression model. RESULTS: The 2 tHcy groups were similar in demographic, stroke, and comorbidity characteristics, differing only by higher frequency of hypertension in those with a tHcy greater than 15 micromol/L (51.7% vs 80.8%, respectively, P=.01). Compared with patients who had tHcy levels at 15 micromol/L or lower and were discharged from rehabilitation being in the highest FIM score group (>80), higher tHcy levels were not associated with a discharge FIM score of less than 40 (odds ratio [OR]=.77; 95% confidence interval [CI], 0.13-4.65; P=.77) or with a better functional outcome FIM score between 40 and 80 (OR=3.71; 95% CI, 0.73-18.99; P=.11). CONCLUSIONS: Our findings suggest that determination of tHcy level does not correlate with functional outcome in patients presenting for rehabilitation after acute ischemic stroke.     

Pregnancy outcome after in utero exposure to angiotensin converting enzyme inhibitors or angiotensin receptor blockers

ObjectiveTo examine first trimester safety of angiotensin-converting-enzyme-inhibitors (ACEIs) or angiotensin-receptor-blockers (ARBs).Study designProspective observational cohort regarding pregnancy ACEI/ARBs-exposure including contacts to two Teratology Information Services in Israel (1994–2007) and Italy (1990–2008), with two comparison groups: (1) exposed to other antihypertensives (OAH) (2) after non-teratogenic exposure (NTE) in similar time frames.Results252 ACEI/ARBs-exposed, 256 OAH-exposed and 495 NTE-exposed pregnancies were followed-up. The rate of major congenital anomalies was comparable between the groups (8/190, 4.2%, ACEI/ARB; 9/212, 4.2%, OAH; 18/471, 3.8% NTE; p = 0.954) among first trimester exposed pregnancies. The median gestational age at delivery was two weeks earlier, rate of preterm deliveries more than 2-fold higher, and median birth weight more than 200 g lower in the ACEI/ARB and OAH groups compared to the NTE group.ConclusionThe present study suggests that ACEI/ARBs are not major teratogens when used in the first trimester, and can reassure women with similar exposures.     

Molecular morphometric analysis shows relative intra-tumoural homogeneity for KRAS mutations in colorectal cancer

KRAS mutation status has a significant role determining anti-epidermal growth factor receptor (anti-EGFR) treatment response in colon carcinoma patients. Malignant transformation is a dynamic process and therefore, it is conceivable that, at a certain point, the tumor cells’ mass might be heterogeneous for particular mutations. Therefore, the fraction of tumor cells carrying a particular mutation may be more relevant for treatment than the simple determination of presence or absence of mutation. The purpose of this study is to assess whether or not KRAS mutation status is heterogeneous and, if so, to what extent in colon carcinoma samples. Deoxyribonucleic acid was extracted from formalin-fixed paraffin-embedded samples of colon carcinoma and analyzed for the presence of KRAS mutation. The relative fraction of mutated versus wild-type KRAS alleles was evaluated by real-time polymerase chain reaction. Additionally, the relative fraction of cancer cells in the tissue sample was evaluated using computer assisted morphometric analysis. Using this data, we calculated the fraction of mutation containing cells in the samples. Colon carcinoma (169 cases) were analyzed, and a KRAS mutation was found in 75 cases (44%), of which 42 were available for morphometric analysis. In 41 (97.6%) of these cases, the fraction of mutation containing tumor cells was 50% or higher, indicating the absence of significant KRAS mutation status heterogeneity. There was a strong positive correlation (R = 0.66, P < 0.0001) between the fraction of mutated KRAS alleles and the fraction of cancer cells in the samples. The strong positive correlation between the fraction of mutated KRAS alleles and the fraction of cancer cells in the samples indicate homogeneity of KRAS mutation status in colorectal carcinoma.     

Examining attitudes, beliefs and knowledge of effective practices in psychiatric rehabilitation in a hospital setting

OBJECTIVE: This brief report presents a staff training program based on psychiatric rehabilitation principles used in a hospital setting. The training program intervention significantly promoted the belief that mental illness does not necessarily limit functioning and also improved awareness of research findings, evidence-based practices and community services. METHODS: A randomized controlled study assessed the impact of the program on the staff's attitudes regarding psychiatric rehabilitation and recovery. RESULTS: Findings suggest that in-service training programs within a hospital setting can change staff attitudes in order to support psychiatric rehabilitation. CONCLUSIONS: A psychiatric rehabilitation forum, made up of representatives from all disciplines, including the medical directors of every ward, was set up in the hospital following the training program and has become the main avenue to disseminate information, messages, and goals to the staff at large and to the hospital administration. It is the forum that creates the shared vision about psychiatric rehabilitation within the hospital and has the task of facilitating implementation of services according to that vision.     

Allelic 'choice' governs somatic hypermutation in vivo at the immunoglobulin kappa-chain locus

Monoallelic demethylation and rearrangement control allelic exclusion of the immunoglobulin kappa-chain locus (Igk locus) in B cells. Here, through the introduction of pre-rearranged Igk genes into their physiological position, the critical rearrangement step was bypassed, thereby generating mice producing B cells simultaneously expressing two different immunoglobulin-kappa light chains. Such 'double-expressing' B cells still underwent monoallelic demethylation at the Igk locus, and the demethylated allele was the 'preferred' substrate for somatic hypermutation in each cell. However, methylation itself did not directly inhibit the activation-induced cytidine-deaminase reaction in vitro. Thus, it seems that the epigenetic mechanisms that initially bring about monoallelic variable-(diversity)-joining rearrangement continue to be involved in the control of antibody diversity at later stages of B cell development.     

Urinary soluble VCAM-1 in systemic lupus erythematosus: a clinical marker for monitoring disease activity and damage

OBJECTIVE: To determine the urinary levels of soluble vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in patients with systemic lupus erythematosus (SLE) and to assess their relationship with clinical and laboratory features and the degree of activity and damage associated with the disease. METHODS: The study sample included 24 consecutive patients with SLE. 24-hour urine samples were collected for the determination of soluble VCAM-1 and ICAM-1 levels by ELISA. Disease activity was defined by the SLE Disease Active Index (SLEDAI) and disease outcome by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ ACR) damage index. RESULTS: The urinary soluble VCAM-1 level was significantly higher in patients with SLE compared to normal controls (32.35+/-34.27 vs. 4.66+/-3.8 ng/mg creatinine, p = 0.0005) and statistically significantly correlated with disease activity (SLEDAI), a low serum C3 level, decreased creatinine clearance and albuminuria, as well as with disease damage (SLICC/ACR damage index). In contrast, the urinary soluble ICAM-1 level was not significantly higher in the patients' group compared with the controls (4.5+/-5.19 vs. 2.72+/-2.31 ng/mg creatinine, p=0.2), but was statistically significantly correlated with hematuria and albuminuria. CONCLUSION: Our data suggest that the urinary level of soluble VCAM-1 significantly correlates with overall disease activity and damage scores, but not with nephritis in SLE.     

NZ51, a ring-expanded nucleoside analog,inhibits motility and viability of breast cancer cells by targeting the RNA helicase DDX3

DDX3X (DDX3), a human RNA helicase, is over expressed in multiple breast cancer cell lines and its expression levels are directly correlated to cellular aggressiveness. NZ51, a ring-expanded nucleoside analogue (REN) has been reported to inhibit the ATP dependent helicase activity of DDX3. Molecular modeling of NZ51 binding to DDX3 indicated that the 5:7-fused imidazodiazepine ring of NZ51 was incorporated into the ATP binding pocket of DDX3. In this study, we investigated the anticancer properties of NZ51 in MCF-7 and MDA-MB-231 breast cancer cell lines. NZ51 treatment decreased cellular motility and cell viability of MCF-7 and MDA-MB-231 cells with IC₅₀ values in the low micromolar range. Biological knockdown of DDX3 in MCF-7 and MDA-MB-231 cells resulted in decreased proliferation rates and reduced clonogenicity. In addition, NZ51 was effective in killing breast cancer cells under hypoxic conditions with the same potency as observed during normoxia. Mechanistic studies indicated that NZ51 did not cause DDX3 degradation, but greatly diminished its functionality. Moreover, in vivo experiments demonstrated that DDX3 knockdown by shRNA resulted in reduced tumor volume and metastasis without altering tumor vascular volume or permeability-surface area. In initial in vivo experiments, NZ51 treatment did not significantly reduce tumor volume. Further studies are needed to optimize drug formulation, dose and delivery. Continuing work will determine the in vitro-in vivo correlation of NZ51 activity and its utility in a clinical setting.     

Primary anetoderma: a cutaneous sign of antiphospholipid antibodies

Although a few reports in recent years have suggested that patients with antiphospholipid antibodies (aPL) are prone to developing primary anetoderma (PA), it is still unclear how often aPL are detected in unselected PA patients. We studied nine consecutive PA patients for the presence of autoimmune antibodies and disorders in general and the presence of aPL in particular. Six of the nine patients had clinical evidence of associated autoimmune disorders (Graves'disease and autoimmune haemolysis in one, systemic scleroderma in one, Hashimoto's thyroiditis in one, alopecia areata in one) and/or signs of hypercoagulability (recurrent fetal loss in two, recurrent stokes in one, recurrent deep vein thrombosis in one). In four ofthese six patients the onset of PA preceded these signs. Positive aPL was found in all: anticardiolipin (aCL) in six, anti-beta2-glycoprotein-I (a(beta)2GPI) in six and lupus anticoagulant (LAC) in four. The most frequent isotype was IgA. Among other autoantibodies found the most frequently was antinuclear antibodies. Four ofthe nine patients fulfilled the criteria for antiphospholipid syndrome (APS). It is concluded that PA is an important cutaneous sign for autoimmune disorders in general and the presence of aPL in particular. Hence, the work-up of these patients should include testing for LAC as well as for all different isotypes ofaCL and a(beta)2GPI. We recommend that PA be added to the list of the cutaneous manifestations of APS.     

Adherence to Guidelines of Pain Assessment and Intervention in Internal Medicine Wards

Proper management of pain reduces morbidity, assists in recovery, and increases patient satisfaction. The role of a nurse in an accurate pain evaluation is pivotal. It seems that pain evaluation guidelines are not fully adhered to by nurses. The aim of this study was to assess the performance of pain evaluation and management by nurses in patients admitted in internal medicine wards and to identify groups of patients in which pain evaluation was insufficient. In this cross-sectional study medical records of 59 randomly chosen patients were reviewed: age 64.5 ± 18.5 years, 55% women, and hopitalization length 3.9 ± 1.6 days. Data relating to pain evaluation and management were obtained for every patient–hospitalization day (total 213 patient-days) and compared with the guidelines. Pain was evaluated in 176 out of 213 encounters (66.2%): 84.3% upon admission and 72.7% daily routine evaluation in accordance with guidelines. In 23.7% of evaluations, pain level warranted alleviating treatment (visual analog scale ≥3). However, such treatment was administered in only 29.3% of these cases. Reevaluation after treatment and additional evaluations thereafter were performed in 33.3% and 22% of encounters, respectively. The independent factors associated with the reduced performance of pain evaluation were: widower (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.78-0.98; p = .024), reduced level of consicousnness (OR 0.77, 95% CI 0.63-0.95; p = .013), mental disorders as a cause of hospitalization (OR 0.81, 95% CI 0.71-0.94; p = .004), and isolation (OR 0.87, 95% CI 0.76-0.99; p = .03). Pain assessment and management in internal medicine wards is insufficient, especially in the above subgroups. Specific education programs targeted to the latter subgroups and to the unique pain assessment tools are warranted.