Effects of acute liver injury on blood coagulation

Summary.  The mechanisms leading to the hemostatic changes of acute liver injury are poorly understood. To study these further we have assessed coagulation and immune changes in patients with acute paracetamol overdose and compared the results to patients with chronic cirrhosis and normal healthy controls. The results demonstrate that in paracetamol overdose coagulation factors (F)II, V, VII and X were reduced to a similar degree and were significantly lower than FIX and FXI (mean levels 0.28, 0.16, 0.13, 0.19, 0.51 and 0.72 IU mL⁻¹, respectively). In cirrhosis, by contrast, FII, FV, FVII, FIX and FX were equally reduced whilst FXI was lower than the other factors (mean levels 0.64, 0.69, 0.62, 0.60, 0.66 and 0.40 IU mL⁻¹, respectively). FVIII was raised in paracetamol overdose patients but normal in those with cirrhosis (mean levels 1.95 and 1.01 IU mL⁻¹, respectively). Interleukin-6 and tumor necrosis factor-α levels were raised in both patient groups, but higher levels were found in paracetamol overdose, compared to cirrhosis. Thrombin-antithrombin and soluble tissue factor levels were higher in those with acute liver injury but normal in cirrhosis. Antithrombin levels were reduced in both acute liver injury and cirrhosis. From these data we put forward a novel mechanism for the coagulation changes in acute paracetamol induced liver injury. We propose that immune activation leads to tissue factor-initiated consumption of FII, FV, FVII and FX, but that levels of FIX and FXI are better preserved because antithrombin inhibits the thrombin induced positive feedback loop that activates these latter factors.     

Influenza vaccination: incidence of symptoms and resulting absenteeism in hospital employees.

A convenience sample of hospital workers, those receiving influenza vaccine and those not receiving vaccine, were asked to complete questionnaires delineating the occurrence of symptoms (e.g., fever, headache, extreme tiredness, dry cough, sore throat, runny nose, stuffy nose, muscle aches) and absenteeism in the 7-day period post-vaccination if vaccinated. Those unvaccinated completed the questionnaire in a self-selected 7 consecutive day period during the study conducted from November 2004 to February 2005. Those receiving either Fluzone or FluMist reported significantly fewer symptoms and related absenteeism than the unvaccinated group (p < .05). Administration of influenza vaccine did not result in higher rates of post-vaccination symptoms as compared to an unvaccinated group. Further, vaccinated employees did not experience higher absenteeism rates as a result of receiving either influenza vaccine. However, for those reporting absenteeism as a result of symptoms, mean absenteeism days were highest in the FluMist group (4.5 days) compared to the unvaccinated group (2.1 days) and the Fluzone group (1.9 days).     

Popliteal artery pseudoaneurysm following total knee arthroplasty: a case report

Direct vascular injury after primary total knee arthroplasty is rare. This case report illustrates a 65-year-old female who was diagnosed with a pseudoaneurysm of the popliteal artery when she was investigated for increased leg swelling and pain 1 week after total knee arthroplasty. She had a percutaneous endovascular repair with a stent after thrombectomy.     

Influence of pain and urinary symptoms on quality of life in young men with chronic prostatitis-like symptoms

BACKGROUND: Our aims in the present study were to estimate the influences of pain and urinary symptoms on quality of life, and to determine which of these two variables has the most predictive power with respect to quality of life in young men with chronic prostatitis-like symptoms. METHODS: Chronic prostatitis-like symptoms were measured by the National Institutes of Health-Chronic Prostatitis Symptom Index. Of the 28,841 men aged 20 years who lived in the study community, 18,495 men (a response rate 64.1%) agreed to participate in the study. A total of 1057 men who complained of symptoms indicative of chronic prostatitis were included in the study. The influences of pain and urinary symptoms on quality of life were determined using logistic regression analysis. The receiver operating characteristic (ROC) curve was used to estimate the predictive ability of each of these variables with respect to quality of life. RESULTS: Results from multivariate analysis showed that both pain and urinary symptoms were associated with an increased likelihood of impaired quality of life, although pain contributed more to a reduced quality of life than urinary symptoms. Relative to men who experienced mild pain, men who experienced moderate pain had a 3.9-fold risk of poor quality of life (odds ratio [OR], 3.87; 95% confidence interval [CI], 2.86-5.23; P < 0.001) and those who experienced severe pain had a 15.7-fold risk of reduced quality of life (OR, 15.68; 95% CI, 6.59-37.35; P < 0.001). Moderate urinary symptoms were associated with a 1.4-fold risk of bother (OR, 1.41; 95% CI, 1.01-1.99; P < 0.001) and severe urinary symptoms were associated with 2.4-fold risk (OR, 2.39; 95% CI, 1.37-4.12; P < 0.001), relative to mild urinary symptoms. Comparison of the effects of pain and urinary symptoms showed that pain severity had the most predictive power for bother, quality of life, and quality-of-life impact. The areas under the ROC curves for bother, quality of life, and quality-of-life impact were 71.3%, 69.3% and 72.5%, respectively. CONCLUSION: Urinary symptoms and pain might be associated with an increased likelihood of impaired quality of life in young men with chronic prostatitis-like symptoms. In addition, our findings suggest that pain severity is the most influential variable for determining quality of life in this population.     

Ketotifen in asthma

Sixty children aged 5-13 years with moderately severe asthma took part in a double-blind, placebo-controlled trial of ketotifen. The design incorporated a 22 week study period, the addition of ketotifen or placebo to the current medication, and a controlled withdrawal of the regular therapy. Children receiving ketotifen showed significantly lower mean numbers of asthma attacks and less absence from school. The addition of ketotifen to existing treatment was associated with marginally significant changes in rates of day and night wheezing. In the second phase of study, additional therapy was withdrawn from both the ketotifen and placebo groups which resulted in a high (percentage) withdrawal. Children receiving ketotifen did not have a significantly lower failure rate than those given placebo.     

Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.

PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.