The association between thrombotic and inflammatory biomarkers and lower‐extremity peripheral artery disease

Lower‐extremity peripheral artery disease (LEAD) is associated with increased rates of mortality and morbidity. The aim of this study was to evaluate the associations among inflammatory and thrombotic markers and lower‐extremity peripheral disease. A total of 280 patients were enrolled in this study. Of these patients, 152 patients had LEAD on peripheral angiography that was performed because of suspected lower‐extremity peripheral disease based on history, physical examination, and non‐invasive tests. The control group consisted of 128 patients without LEAD on peripheral angiography. Patients with LEAD were classified according to trans‐atlantic inter‐society consensus (TASC) II classification. Subsequently, patients in TASC A to B were defined as having mild to moderate peripheral artery disease, and those in TASC C to D were defined as having advanced peripheral artery disease. Thrombotic and inflammatory markers, such as the neutrophil‐to‐lymphocyte ratio (NLR), the high‐sensitivity C (hs‐C) reactive protein level, the monocyte‐to‐high‐density lipoprotein‐cholesterol ratio, the fibrinogen to albumin ratio (FAR), and whole‐blood viscosity at high shear rate (HSR) and low shear rate (LSR), were evaluated in this population. The NLR, the monocyte‐to‐high‐density lipoprotein‐cholesterol ratio, the FAR, and whole‐blood viscosity, both at a LSR and a HSR, were significantly higher in patients with lower‐extremity peripheral disease compared with patients without lower‐extremity peripheral disease. We determined that lower‐extremity peripheral disease severity was correlated with the NLR, monocyte‐to‐high‐density lipoprotein‐cholesterol ratio, FAR, whole‐blood viscosity at LSR, and whole‐blood viscosity at HSR (r = 0.719, P = .004; r = 0.25, P = .008; r = 0.691, P = .002; r = 0.546, P < .001; and r = 0.448, P = .001, respectively). However hs‐C reactive protein levels were similar between patients with or without LEAD (2.47 ± 1.32 1.61 ± 0.91 P = .685). In addition, there was no correlation between the severity of LEAD and hs‐C reactive levels. In this study, we determined that the levels of inflammatory and thrombotic biomarkers are elevated in peripheral artery disease, and these levels predict disease severity.     

The liver in infectious mononucleosis

Summary 1. Twenty-two patients with infectious mononucleosis were studied by liver biopsy and paper electrophoresis of the serum proteins. The findings were compared with a similar group of 30 patients with infectious hepatitis.2. The essential histologic features of infectious mononucleosis were the presence in the hepatic sinusoids and portal tracts of chronic inflammatory cells resembling small lymphocytes, with essentially no parenchymal cell damage. Admixed with this lymphocytic infiltrate, but in relatively minimal numbers, were a few plasma cells and polymorphonuclear leukocytes. In addition, in infectious mononucleosis there were, with rare exceptions, no lipochrome-containing Kupffer cells. Thus, in the majority of cases, the histologic picture was distinct from that seen in infectious hepatitis. Only in comparing a few of the more severe infectious mononucleosis cases with subsiding infectious hepatitis cases was there any tendency for the two pictures to merge, and the distinction on histologic grounds between the two entities could be made in the great majority of cases.3. The most commonly seen abnormalities in the paper electrophoretic patterns of sera obtained from patients with infectious mononucleosis were decreased albumin, increased gamma globulin, not infrequent but variable changes in alpha₂ globulin, and the presence of abnormal proteins migrating with mobilities intermediate to alpha₂ and beta, and beta and gamma globulins. The abnormalities observed in infectious hepatitis were similar to those of infectious mononucleosis, except that in hepatitis alpha₂ globulin was decreased more consistently, gamma globulin increased less frequently, and beta globulin, which was normal in practically all the cases of infectious mononucleosis, was increased in a considerable number of cases.4. Treatment of patients with infectious mononucleosis need not include prolonged bed rest and restriction of activity in an effort to avoid the development of chronic liver disease.     

Common sense in the treatment of pilonidal disease

Summary The management of pilonidal cyst disease in a large military hospital is described. Of special interest to the military practice is the “buddy” system, in which patients help one another to keep their wounds clean and dry. The specific objectives of our technic are: 1) obtaining excellent hemostasis by the use of zinc peroxide paste; 2) avoiding recurrences by an open-wound method of treatment; 3) preservation of a pad of subcutaneous tissue over the postsacral fascia, thus reducing long-term morbidity by insuring a mobile scar; 4) decreasing the duration of hospitalization, achieved by frequently drying the wounds with warm air. Read at the meeting of the American Proctologic Society, Hollywood, Florida, April 12 to 16, 1970. The opinions or assertions contained herein are those of the authors and are not to be construed as official or as reflecting the views of the Navy Department.     

Sustained seroconversion of chronic hepatitis B infection after stem cell transplantation

Serap A, Funda O, Bengu K, Mehmet K, Nazan C, Rasit Y, Savas K. Sustained seroconversion of chronic hepatitis B infection after stem cell transplantation.
Pediatr Transplantation 2011: 15: E92–E95. © 2010 John Wiley & Sons A/S. Abstract: We present an 18‐yr‐old adolescent with acute lymphocytic leukemia, who underwent peripheral blood SCT with serologically and histologically documented chronic hepatitis B infection. Prior and during the transplant process, lamivudine was administered orally and he underwent SCT with a twofold decrease in viral load at the time of transplant from his HLA full matched, HBV natural immune (anti‐HBs and anti‐HBc positive) donor. Successful engraftment was achieved and three months after SCT, HBV seroconversion was documented accompanied with an ALT flare. Chronic graft‐versus‐host disease coincided after the transplantation, and he has been on immunosuppressive treatment for 25 months with sustained HBV seroconversion. We assume that adoptive immunity transfer combined with antiviral treatment might also constitute sustained seroconversion in chronic HBV, besides the reported risk of reactivation.     

Association between TNF-alpha -308G>A polymorphism and the development of acute coronary syndromes in Greek subjects: the CARDIO2000-GENE Study.

PURPOSE: We investigated the association of a polymorphism within the promoter of TauNuF-alpha locus at the position -308 on the likelihood of having acute coronary syndromes (ACS) in Greek adults. METHODS: We studied demographic, lifestyle, and clinical information in 237 hospitalized patients (185 males) with a first event of an ACS and 237 matched by age and sex (controls) without any clinical evidence of coronary heart disease. Genotyping was performed by PCR-RFLP analysis. RESULTS: The genotype frequencies were in patients, 87% (n = 206), 12% (n = 29), and 1% (n = 2) for G/G, G/A, and A/A, and in controls, 96% (n = 227), 4% (n = 10), and 0% (n = 0) for G/G, G/A, and A/A, respectively (P = 0.04). After adjusting for age and sex, as well as various potential confounders, we observed that G/A or A/A genotypes were associated with 1.94-fold higher odds (95% CI 1.06 to 3.68) of ACS compared to G/G homozygotes. No gene to-gender or to-clinical syndrome interactions were observed. Further subgroup analysis showed that the distribution of TNF-alpha -308G>A polymorphism was associated with the presence of family history of CHD in patients, but not in controls. In particular, in G/A and A/A patients 17.2% reported family history of CHD, whereas in G/G patients, 34.5% reported family history (P = 0.036). CONCLUSIONS: Our findings may state a hypothesis of an association between the -308G>A TNF-alpha polymorphism the development of ACS and the presence of family history of CHD, in Greece.     

P-glycoprotein-mediated multidrug resistance and lymphokine-activated killer cell susceptibility in ovarian carcinoma

The sensitivity of tumor cells to lysis by natural killer (NK) and interleukin-2 (IL-2)-activated killer (LAK) cells was studied in three ovarian carcinoma cell lines (2780.9S, SKOV-3, and CHOAUXB1), four multidrug-resistant (MDR) variants, and a melphalan-resistant line. The antitumor activity of LAK cells was evaluated both by⁵¹Cr release and by conjugate formation assays. Four of four P-glycoprotein-positive (P-gp⁺) MDR ovarian carcinoma cell line variants were lysed by human LAK cells to a greater extent than were their drug-sensitive counterparts. In contrast, a melphalan-resistant ovarian carcinoma cell line that does not overexpress P-gp (P-gp^–) did not exhibit an increased susceptibility to LAK cells relative to its parental cell line. Two of the four P-gp⁺ MDR ovarian carcinoma cell line variants were tested for human NK cell susceptibility and this was found to be unchanged or decreased. The P-gp⁺ MDR ovarian carcinoma cell line 2780.AD645 showed a higher frequency of tumor cell binding to LAK cells than did the drug-sensitive parental line. A monoclonal antibody (mAb) against a cell surface epitope of P-gp, MRK16, used at 1 g/ml, enhanced the LAK susceptibility of P-gp⁺ MDR ovarian carcinoma cell lines. However, when incubation with 10 g/ml MRK-16 antibody (Ab) was followed by 12.5 g/ml F(ab)₂ goat anti-mouse (GAM) immunoglobulin (Ig), the increased LAK susceptibility of P-gp⁺ MDR cell lines was inhibited. These data strongly suggest that P-glycoprotein-positive MDR ovarian carcinoma cells not only are targets for LAK cells, but are more sensitive than their drug-sensitive parental lines. This is in contrast to their susceptibility to NK cells, which is low to start with and remains unchanged or even decreased in MDR cells. It is postulated here that P-gp or associated changes result in a greater frequency of effector-target cell binding, leading to increased LAK cell cytotoxicity.     

Oxidative stress and enzymatic antioxidant status in patients with nonalcoholic steatohepatitis

Oxidative stress is an important pathophysiological mechanism in nonalcoholic steatohepatitis (NASH). To assess whether there are relationships between oxidative stress and antioxidant enzymes in the development of NASH, we investigated oxidative stress by measuring serum malondialdehyde (MDA) and nitric oxide (NO) and antioxidant status by measuring serum glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and superoxide dismutase (SOD). The study included 18 patients (13 men, 5 women; mean age 42 yr) with biopsy proven NASH and 16 healthy volunteers (10 men, 6 women; mean age 38 yr). Serum levels of MDA, NO, GSH, GSH-Px, GR and SOD were determined by spectrophotometric methods. Serum levels (mean +/- SD) of MDA (6.7 +/- 1.6 vs 2.8 +/- 1.7 nmol/ml, p 0.0001), NO (135 +/- 28 vs 113 +/- 35 mmol/L, p 0.04), GSH (919 +/- 137 vs 770 +/- 128 mmol/L, p 0.003) were increased in patients with NASH vs controls. Serum levels of GSH-Px (1063 +/- 152 vs 1000 +/- 94 U/L) and GR (47 +/- 22 vs 40 +/- 21 U/L) were not singnificantly different in the patients vs controls. However, the serum level of SOD (1.24 +/- 0.32 vs 1.51 +/- 0.37 U/ml, p: 0.04) was significantly decreased. Impaired antioxidant defense mechanisms may be an important factor in the pathogenesis of NASH. Treatment approaches that affect the antioxidant enzymes may be beneficial in patients with NASH.