Evidence of an increased nitric oxide production in primary biliary cirrhosis

OBJECTIVE: Although possible implications of nitric oxide in the pathophysiology of liver cirrhosis have been extensively studied, until now few articles have addressed the assessment of nitric oxide production in primary biliary cirrhosis. This study was directed to evaluate circulating nitrosyl-hemoglobin levels as well as neutrophil elastase and soluble adhesion molecule concentrations in this condition, by assuming these parameters as possible markers of either inflammatory response or neutrophil activation. METHODS: Laboratory investigations were performed in 30 patients with primary biliary cirrhosis, in 13 patients with postviral and/or alcoholic cirrhosis, and in a group of eight subjects with chronic hepatitis. RESULTS: Although no difference was detected with respect to chronic hepatitis subjects, higher levels of nitrosyl-hemoglobin adducts were found in primary biliary cirrhosis patients than in postviral or alcoholic cirrhotics and in normal subjects (3.55+/-1.75 arbitrary units vs 1.95+/-0.57 and 0.84+/-0.34, p = 0.0004 and p < 0.0001, respectively). Similarly, more elevated concentrations of neutrophil elastase (213.7+/-192.0 microg/L vs 51.1+/-34.3 and 38.0+/-11.5, p < 0.0001 and p < 0.0001, respectively) as well as of soluble forms of intercellular adhesion molecule 1 and endothelial-leukocyte adhesion molecule 1 were shown in primary biliary cirrhosis patients than in subjects with cirrhosis of other etiologies and in controls. CONCLUSIONS: Highly enhanced nitric oxide production in primary biliary cirrhosis could be related to the development of strong inflammation and at least partially to neutrophil activation, thus suggesting a putative role of these cellular mediators in the development of liver damage owing to their ability to synthesize and release a wide variety of important factors, including elastase and nitric oxide.     

Nosocomial infections in critically ill infectious disease patients: Results of a 7-year focal surveillance

Summary An incidence study on nosocomial infections in critically ill infectious disease patients was carried out in the intensive care unit (ICU) of a university hospital for infectious diseases over a 7-year period (1 January 1990 to 31 December 1996). A total 660 patients who stayed in the ICU for over 48 h were prospectively observed. The patients were divided into two groups: one with central nervous system infections (442 patients) and the other with other severe infections (218 patients). The risk of nosocomial sepsis and pneumonia was significantly higher in patients suffering from severe central nervous system infections. The incidence of sepsis was 24.2% vs 11.4% (relative risk 1.95; 95% confidence interval 1.32–2.89); the incidence of pneumonia was 30.5% vs 14.7% (relative risk 2.09; 95% confidence interval 1.47–2.96). The incidence of urinary tract infection was 14.3% vs 13.3% (relative risk 1.07; 95% confidence interval 0.71–1.61). Density rates of nosocomial septic episodes were 21.1±37.1 vs 11.7±32.4 episodes/100 central venous-line days (P<0.006). Nosocomial pneumonia occurred only in mechanically ventilated patients (36.9±61.2 vs 28.5±65.8 episodes per 1000 ventilatory days, P=0.012). Nosocomial urinary tract infection occurred only in patients with urinary catheters (11.6±60.7 episodes/1000 urinary catheter days vs 18.7±90.1, P=0.886). Multivariate regression analysis identified age, diagnosis of CNS infection, duration of urinary tract catheterization, the use of central venous lines and mechanical ventilation as independent risk factors of nosocomial sepsis. Duration of mechanical ventilation, use of steroids and diagnosis of CNS infection were independent risk factors of nosocomial pneumonia. A subanalysis identified tetanus patients to be at particular risk of nosocomial infections.     

The in vitro treatment with vitamin D3 is ineffective on the expression of PKC isoenzymes,but decreases further the impaired production of IL-2 in the T lymphocytes of SLE patients

The objective of the study was to investigate the possibility whether the in vitro treatment with vitamin D₃ can restore the impaired expression of protein kinase C (PKC) isoenzymes and IL-2 production in the lymphocytes of patients with systemic lupus erythematosus (SLE). Purified T lymphocytes from 14 patients with SLE and 13 healthy controls were cultured for 48 h in the presence and absence of 1 and 100 nM doses of vitamin D₃. The expressions of various PKC isoenzymes were tested by Western blot analysis, and the amounts of various cytokines were detected by ELISA in the culture supernatants. Neither the low (1 nM) nor the high (100 nM) doses of vitamin D₃ (1α,-25-dihydroxyvitamin) applied in vitro for 48 h were able to restore the decreased expression of PKC isoenzymes in the T cells of SLE patients. However, 100 nM of vitamin D₃ significantly increased the release of IL-10, but suppressed the production of IL-2, IL-6, interferon γ and TNF α in the culture supernatants of both groups. As the low production of IL-2 is one of the main pathologic features of SLE, we recommend to avoid the use of high doses of vitamin D₃ for treatment of lupus patients with vitamin D₃ deficiency.     

Elderly deaths in Ankara,Turkey

According to World Health Organization, the life expectancy at birth is increasing. An increase in life expectancy might result in increased morbidity and mortality in elderly. The increase in the elderly population also leads to an increase in medico-legal problems, as well. Autopsy is of high importance for determination of cause of death in clinical and forensic cases. The purpose of this study was to find out general characteristics elderly deaths by examining forensic autopsy records.     

EGFR Mutation Testing Practice in Advanced Non-Small Cell Lung Cancer

Purpose

Testing tumor samples for the presence of a mutation in the epithelial growth factor receptor (EGFR) gene is recommended for advanced non-squamous non-small cell lung cancer (NSCLC) patients. We aimed to collect data about common practice among Medical Oncologists treating lung cancer patients, regarding EGFR mutation testing in advanced NSCLC patients.

Methods

An internet-based survey was conducted among members of the Israeli Society for Clinical Oncology and Radiotherapy involved in the treatment of lung cancer patients.

Results

24 Oncologists participated in the survey. The participants encompass the Oncologists treating most of the lung cancer patients in Israel. 79 % of them use EGFR testing routinely for all advanced NSCLC patients. Opinions were split regarding the preferable biopsy site for EGFR testing material. 60 % of participants recommend waiting for EGFR test results prior to initiation of first-line therapy.

Conclusions

EGFR testing is requested in Israel routinely by most treating Oncologists for all advanced NSCLC patients, regardless of histology. In most cases, systemic treatment is deferred until the results of this test are received.     

Elevated levels of RDW is associated with non-valvular atrial fibrillation

Red cell distribution width (RDW) and neutrophil/lymphocyte ratio (NLR) have been found to be associated with cardiovascular diseases. Only a few trials have investigated the correlation of these parameters with postoperative atrial fibrillation (AF). However, the correlation of these parameters in non-valvular AF is still unclear. We retrospectively analyzed consecutive AF patients from medical records and included 117 non-valvular AF patients (103 paroxysmal and 14 chronic AF). All subjects underwent physical examination and echocardiographic imaging. Complete blood counts (CBCs) were analyzed for hemoglobin, RDW, neutrophil and lymphocyte counts as well as mean corpuscular volume. Results of CBC tests within the previous year were also included and the averages were used. The demographic and echocardiographic properties of non-valvular AF group were comparable to the control group except for left atrial volumes which were increased in AF (median 33.1, IQR 26.3–41.1 cm³ vs. median 26.4, IQR 24.2–28.9 cm³; p = 0.01). RDW levels were significantly higher in the AF group (median 13.4 %, IQR 12.9–14.1 %) compared to the control (median 12.6 %, IQR 12.0–13.1 %; p = 0.01). NLR was not statistically different in the AF group and the controls (2.04 ± 0.94 vs. 1.93 ± 0.64, respectively; p = 0.32). Hs-CRP levels were higher in the AF group compared to the controls (median 0.84, IQR 0.30–1.43 mg/L vs. median 0.29, IQR 0.18–0.50 mg/L, respectively; p = 0.01). Multivariate logistic regression analysis revealed RDW (OR 4.18, 95 % CI 2.15–8.15; p = 0.01), hs-CRP (OR 3.76, 95 % CI 1.43–9.89; p = 0.01) and left atrial volume (OR 1.31, 95 % CI 1.06–1.21; p = 0.01) as the independent markers of non-valvular AF. Multivariate linear regression analysis revealed that hemoglobin levels (standardized β coefficient = ?0.252; p = 0.01) and the presence of AF (standardized β coefficient = 0.336; p = 0.01) were the independent correlates of RDW levels. Elevated RDW levels, not NLR, may be an independent risk marker for non-valvular AF.     

“Vanishing liver metastases”—A real challenge for liver surgeons

Expanded surgical intervention in colorectal liver metastasis (LM) and improved chemotherapy led to increasing problem of disappearing liver metastases (DLM). Treatment of those continues to evolve and poses a real challenge for HPB surgeons. This review discusses a clinical approach to DLM, emphasizing crucial steps in clinical algorithm. Particular issues such as imaging, intraoperative detection and surgical techniques are addressed. A step-by-step algorithm is suggested.     

Evaluation of Systemic Levels of Neutrophilic Enzymes in Patients With Hypertension and Chronic Periodontitis

Background: Inflammation stimulates neutrophils to release their enzymes into the extracellular matrix. The aim of the present study is to investigate the serum levels of matrix metalloproteinase (MMP)‐8, MMP‐9, tissue inhibitor of MMP (TIMP)‐1, myeloperoxidase (MPO), and neutrophil elastase (NE) in patients with hypertension and chronic periodontitis (CP). Methods: A total of 95 patients were included in the study. Patients were categorized into three groups: healthy control (n = 29), hypertensive control (n = 32), and hypertensive CP (n = 34). Periodontal parameters were recorded, and serum samples were collected from each participant. Serum MMP‐8, MMP‐9, TIMP‐1, MPO, and NE levels in circulation were assessed by enzyme‐linked immunosorbent assay. Results: The hypertensive CP group had significantly higher serum MMP‐8, MMP‐9, and NE levels than the healthy control group (P <0.05). All study groups had similar serum TIMP‐1 levels (P >0.05). Significantly higher serum MPO levels were detected in patients with hypertension and CP than healthy controls and hypertensive controls (P <0.05); however, the difference in serum MPO levels was not significant between the healthy controls and hypertensive controls (P >0.05). There was no significant difference in MMP‐8/TIMP‐1 ratio among the study groups (P >0.05). MMP‐9/TIMP‐1 ratio was significantly higher in patients with hypertension and CP than healthy controls (P <0.05). Conclusions: The presence of hypertension along with CP has a considerable effect on serum neutrophilic enzyme levels, except TIMP‐1. However, the levels of these enzymes do not seem to be affected by the presence of hypertension only. Further studies including patients who have only CP might help illuminate the effect of CP on these enzymes in patients with hypertension.