High frequency of Fredrickson's phenotypes IV and IIb in Brazilians infected by human immunodeficiency virus

Background  

Human immunodeficiency virus (HIV) infection is very prevalent in Brazil. HIV therapy has been recently associated with coronary heart disease (CHD). Dyslipidemia is a major risk factor for CHD that is frequently described in HIV positive patients, but very few studies have been conducted in Brazilian patients evaluating their lipid profiles.     

Hematologic and immunomodulatory effects of an interleukin-1 receptor antagonist coinfusion during low-dose endotoxemia in healthy humans

Endotoxin is a component of gram-negative bacteria that causes hematologic and immunologic changes through its induction of cytokines. Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1 that competes with IL-1 for occupancy of cell-surface receptors but possesses no agonist activity. We investigated the ability of human recombinant IL-1Ra to block the effects of low-dose endotoxin. Fourteen healthy male volunteers between 18 and 30 years old were injected intravenously with 3 ng/kg Escherichia coli endotoxin. Concurrent with the injections, nine volunteers received a 3-hour continuous intravenous infusion of IL-1Ra. The other five subjects were given a 3-hour infusion of saline. Volunteers injected with endotoxin experienced a threefold increase in circulating neutrophils over baseline. This neutrophilia was significantly reduced by 48% in subjects administered endotoxin plus IL-1Ra (P = .0253). Ex vivo mitogen-induced peripheral blood mononuclear cell proliferation decreased by greater than 60% at 3 and 6 hours after endotoxin injection (P = .0053). This endotoxin-induced reduction in mitogen response was reversed in subjects coinjected with IL-1Ra (P = .0253). Endotoxin-induced symptoms, fever, and tachycardia were unaffected by IL-1Ra. IL-1 appears to be an important mediator in endotoxemia because some of its hematologic and immunomodulatory effects can be blocked by IL-1Ra.     

Dependence of enhanced maximal exercise performance on increased peak skeletal muscle perfusion during long-term captopril therapy in heart failure

Maximal oxygen uptake (VO2), skeletal muscle blood flow by xenon-133 washout technique and femoral vein arteriovenous oxygen difference and lactate were measured at rest and during maximal bicycle exercise in eight patients with severe congestive heart failure before and after 8 weeks of therapy with captopril. During therapy, skeletal muscle blood flow at rest increased significantly from 1.5 +/- 0.6 to 2.6 +/- 1.0 ml/100 g per min (p less than 0.05), with a concomitant decrease in the femoral arteriovenous oxygen difference from 10.0 +/- 1.7 to 8.3 +/- 1.9 ml/100 ml (p less than 0.05). Maximal VO2 increased significantly from 13.4 +/- 3.0 to 15.5 +/- 4.1 ml/kg per min (p less than 0.05). In four patients, the increase in maximal VO2 averaged 3.7 ml/kg per min (range 2.7 to 4.9), whereas in the remaining four patients, it was less than 1 ml/kg per min. Overall, peak skeletal muscle blood flow attained during exercise did not change significantly during long-term therapy with captopril (19.6 +/- 6.2 versus 27.6 +/- 14.3 ml/100 g per min, p = NS). However, the four patients with a significant increase in maximal VO2 experienced substantial increases in peak skeletal muscle blood flow and the latter changes were linearly correlated with changes in maximal VO2 (r = 0.95, p less than 0.001). Femoral arteriovenous oxygen difference at peak exercise was unchanged (12.6 +/- 2.6 versus 12.6 +/- 2.4 ml/100 ml). Thus, improvement in maximal VO2 produced by long-term therapy with captopril is associated with an increased peripheral vasodilatory response to exercise, and this improvement only occurs when the peak blood flow is augmented.(ABSTRACT TRUNCATED AT 250 WORDS)     

Etoposide causes illegitimate V(D)J recombination in human lymphoid leukemic cells

Etoposide is one of the most widely used antineoplastics. Unfortunately, the same treatment schedules associated with impressive efficacy are associated with an increased risk of secondary acute myeloid leukemia (AML), which has prompted its withdrawal from some treatment regimens, thereby potentially compromising efficacy against the original tumor. Because etoposide-associated AML is characterized by site-specific illegitimate DNA recombination, we studied whether etoposide could directly cause site-specific deletions of exons 2 and 3 in the hprt gene. Human lymphoid CCRF-CEM cells were treated with etoposide for 4 hours, and DNA was isolated after subculturing. The deletion of exons 2 and 3 from hprt was assayed by a quantitative polymerase chain reaction (PCR) method. In the absence of etoposide treatment, the frequency of deletions of exons 2 and 3 was very low (5.05 x 10(-8)). After exposure to 10 mumol/ L etoposide, the frequency of the exon 2 + 3 deletion was increased immediately after and at 24 hours after etoposide treatment (65 to 89 x 10(-8)) and increased to higher levels (128 to 173 x 10(-8)) after 2 and 6 days of subculture (P < .001 overall). The frequency of the exon 2 + 3 deletion assessed at 6 days of subculture after 4 hours of 0, 0.25, 1, 2.5, 5, and 10 mumol/L etoposide treatment increased with etoposide concentration, ie, 5.05 x 10(-8), 89.2 x 10(-8), 108 x 10(-8), 142 x 10(-8), 163 x 10(-8), and 173 x 10(-8), respectively (P < .0001). Sequencing of a subset of amplified products confirmed the presence of DNA sequences at the breakpoints consistent with V(D)J recombination. By contrast, exon 2 + 3 deletions after etoposide treatment in the myeloid cell lines KG-1A and K562 showed no evidence of V(D)J recombinase in their genesis. We conclude that etoposide can induce the illegitimate site-specific action of V(D)J recombinase on an unnatural DNA substrate after a single treatment in human lymphoid cells.     

The effect of improvement in diabetic control on plasma and whole blood viscosity

Summary Rheological studies were made on the blood of 12 diabetic patients after a period of poor diabetic control (HbA₁ 12.6±0.7% (mean ± SD); mean home capillary blood glucose level 11.7±1.2 mmol/l), and after at least three months of improved control (HbA₁ 9.1±0.4%, p<0.01; mean home capillary blood glucose level 9.2±0.6 mmol/l). There were significant decreases in plasma fibrinogen levels (4.1±0.6 to 3.7±0.6 g/l, p <0.01), plasma viscosity (1.31±0.1 to 1.25±0.04, p<0.001), and whole blood viscosity at low (22.8±2.7 to 20.2±2.9, p<0.01) and high shear rates (3.4 ±0.2 to 3.1±0.2, p<0.01). Ten diabetics with clinically evident complications were matched with diabetics of similar age, sex, duration and current control of diabetes. There were no significant differnces in plasma or whole blood viscosities between the two groups. Hyperviscosity in diabetes seems strongly related to hyperglycaemia and to be influenced by the quality of diabetic control.     

Cholangiocarcinoma and High-Grade Dysplasia in Young Patients with Primary Sclerosing Cholangitis

Introduction

Cholangiocarcinoma (CCA) is very often an adulthood disease with primary sclerosing cholangitis (PSC) as one of the risk factors. It is rarely seen in the pediatric population, and when it is diagnosed before adulthood, it can be associated with PSC as well as HIV infection, biliary atresia, radiation therapy, and choledochal cyst. Although there have been some case reports of pediatric CCA, cases of childhood CCA associated with PSC are still relatively rare.

Aim

To describe the clinical and pathologic features of CCA in pediatric patients with previously diagnosed PSC.

Methods

Retrospective study

Results

Four patients with PSC (age range 15–18, mean 17 years) were included in this study. All patients underwent ERCP for diagnosis. Tissue samples obtained included routine cytology and FISH. ERCP was used to target sites for tissue acquisition in all patients. 3/4 of patients have inflammatory bowel disease (two Crohn’s disease and one ulcerative colitis). Alkaline phosphatase was elevated in 3/4 patients, aspartate aminotransferase/alanine aminotransferase were elevated in 2/4 patients, and total bilirubin/direct bilirubin were elevated in 2/4 patients. 4/4 patients had positive FISH studies, and 3/4 patients had brush cytology concerning for CCA. 2/4 patients received chemotherapy, one patient underwent orthotopic liver transplant, and one patient underwent Whipple procedure. Two patients died soon after being diagnosed.

Conclusions

Young patients with PSC can develop CCA. This finding has implications for both screening and surveillance for cancer in pediatric patients with PSC.     

Recruitment evaluation of a preschooler obesity-prevention intervention

The aim of this paper was to compare the recruitment strategies of two recent studies that focused on the parental influences on childhood obesity during the preschool years. The first study was a randomised controlled trial (RCT) of the Mind, Exercise, Nutrition?…?Do It! 2–4 obesity prevention programme and the second was a longitudinal cohort study. For both studies, the desired population were families with preschool children at risk of developing overweight or obesity. Hence, families from diverse ethnic and socio-economic backgrounds were sought. Funding for the RCT provided the resources to adopt a targeted approach to recruitment whereas for the longitudinal study, recruitment was random and opportunistic, rather than specific and targeted. The RCT reported higher child body mass index-for-age z scores, more families not from an Australian or New Zealand background, and more families in the lowest income bracket, suggesting that strategically targeted approaches to recruitment are more likely to achieve the desired sample.     

Significance of atypia in pancreatic and bile duct brushings: Follow‐Up analysis of the categories atypical and suspicious for malignancy

Brushing cytology is frequently utilized for the investigation of pancreatic and biliary strictures but is associated with low diagnostic sensitivity. The Papanicolaou Society of Cytopathology has presented a system for diagnostic classification which includes the categories benign, atypical, suspicious for malignancy and malignant. We studied a series of 216 pancreatic and biliary brushings with either histologic follow‐up or a minimum of 6 months clinical follow‐up to determine outcomes for the diagnostic categories (“benign,” “atypical, favor reactive,” “atypical, not otherwise specified,” “atypical, suspicious” and “malignant”). Eighty‐six of the 216 (39.8%) were designated “atypical” with 10 of these designated as “atypical favor reactive.” Forty‐five were called “atypical not otherwise specified” and 31 were interpreted as “atypical suspicious for malignancy.” On follow‐up, 2 of 10 (20%) “atypical favor reactive” were eventually associated with a malignant diagnosis and 23 of 31 (74.2%) “atypical, suspicious for malignancy” demonstrated a malignant outcome. The remaining 45 brushings in the “atypical” category were “atypical not otherwise specified,” and 62% of these were associated with malignancy on follow‐up. Stratification of the “atypical” category into “atypical favor reactive,” “atypical, not otherwise specified” and “atypical, suspicious for malignancy” improves diagnostic accuracy. The “atypical suspicious for malignancy” category has a follow‐up similar to the “malignant” category while the “atypical favor reactive” category is associated with a clinical outcome similar to that of the “benign” category. Diagn. Cytopathol. 2014;42:285–291. © 2013 Wiley Periodicals, Inc.