Donor levels of serum alanine aminotransferase activity and antibody to hepatitis B core antigen associated with recipient hepatitis C and non- B, non-C outcomes

BACKGROUND: Hepatitis virus(es) that are neither hepatitis B (HBV) nor hepatitis C (HCV) (non-B, non-C [NBNC]) may be transmitted by transfusion. The present study assessed donor values for alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti- HBc) for their association with HCV and NBNC hepatitis outcomes among allogeneic blood recipients. STUDY DESIGN AND METHODS: Data on blood donors and recipients enrolled in the Transfusion- Transmitted Viruses Study in four United States cities from 1974 through 1980 were supplemented by anti-HBc testing of donors and anti-HCV evaluation of recipients. Two statistical approaches estimated the value of these indirect tests in detecting donors associated with HCV seroconversion and NBNC hepatitis in recipients. RESULTS: For HCV cases, donor ALT alone (at > or = 60 IU/L) had a sensitivity and a specificity of 30 and 96 percent, respectively, and anti-HBc alone (at > or = 60% inhibition) had a sensitivity and specificity of 53 and 86 percent, respectively. The two markers combined had a sensitivity and a specificity of 69 and 83 percent. For NBNC hepatitis cases, each measure had low sensitivity (20%) that was not improved by using both (28%) [corrected]. CONCLUSION: The indirect tests proved to be equal in sensitivity to the first-generation anti-HCV tests. The positive predictive power of these indirect tests in the 1980s was sufficient to affect HCV incidence in studies during that period. Improved anti-HCV assays, however, replaced the need for indirect tests. The sensitivity of indirect tests for NBNC hepatitis contributed little.     

Effect of autologous serum on human leucocyte Na+/H+ exchange and intracellular pH

1. Leucocyte Na+/H+ exchange and intracellular pH were investigated in physiological buffer containing bicarbonate. 2. The amiloride analogue 5-(N,N-hexamethylene) amiloride (1 x 10(-5) mol/l), an inhibitor of Na+/H+ exchange, had no significant effect on resting leucocyte pH, Na+ influx or Na+ content. 3. Ammonium chloride washout induced a profound intracellular acidosis, stimulating Na+/H+ exchange. This led to a 236% increase in Na+ influx. Eighty-eight per cent of this increase was inhibited by 5-(N,N-hexamethylene) amiloride. This demonstrates that 5-(N,N-hexamethylene) amiloride is an effective inhibitor of Na+/H+ exchange in human leucocytes. 4. The recovery from intracellular acidosis was shown to be dependent entirely on the presence of extracellular Na+. The Ki for inhibition by 5-(N,N-hexamethylene) amiloride of the recovery was 0.5 mumol/l. 5. Incubation with serum increased Na+ influx and Na+ content: the maximal effect was reached at 20% dilution. Serum (10%, v/v) increased influx by 40%, and 20% (v/v) serum by 102%, over resting levels. Only 43% of the serum-induced increase in Na+ influx was inhibited by 5-(N,N-hexamethylene) amiloride. This represented one-fifth of total Na+ influx. 6. Leucocyte intracellular pH increased on incubation with serum. This alkalinization was inhibited using 5-(N,N-hexamethylene) amiloride. 7. Studies of Na+/H+ exchange in leucocytes in physiological and pathological states are more likely to reflect the state in vivo if carried out in the presence of autologous serum.     

Induced sputum for the diagnosis of pulmonary tuberculosis: Is it useful in clinical practice?

BACKGROUND:

Diagnosing pulmonary tuberculosis (PTB) is challenging in patients who are unable to spontaneously expectorate. Published evidence suggests that induced sputum (IS) is the least invasive and most cost-effective method of diagnosis, and should be used before fibre-optic bronchoscopy (FOB).

METHODS:

The medical records of 337 adults treated for PTB in northern Alberta between 1997 and 2007 were reviewed to determine whether local practice patterns reflect the evidence. Microbiological data were collected from the Provincial Laboratory for Public Health. Demographic information was collected from the patients’ charts.

RESULTS:

A total of 8.5% (26 of 307) of PTB patients had IS collected, whereas 35.8% (110 of 307) underwent FOB. Among FOB patients, 56.4% (62 of 110) had no sputum sent before the procedure and 29% (18 of 62) of these patients were smear positive. Only five patients referred for FOB had IS sent previously. There were no demographic factors predictive of IS use, whereas being an inpatient at a teaching facility or having a nodule or mass on chest x-ray was predictive of FOB referral. Because so few IS samples were available, not all patients had spontaneously expectorated sputum, IS and FOB tests performed; thus, the calculated yields were not comparable with one another.

CONCLUSIONS:

Despite published evidence recommending IS collection before FOB referral in suspected PTB patients, clinicians in our health region appeared to prefer early FOB over IS by a large margin. This practice pattern is less cost effective and exposes patients and health care workers to greater risk. Further research is needed to identify the reasons for the underuse of sputum induction.     

Treatment of obesity in the primary care setting: are we there yet?

Obesity is a significant public health issue in the US constituting an independent risk factor for morbidity and mortality as well as complicating the management of other medical conditions. Yet, traditionally most physicians receive little training in evidence-based obesity interventions. Previous literature suggests many physicians believe they do not have effective tools to address obesity and/or that obesity management is not within their scope of practice. Given the new emphasis from NIH and AAFP urging physicians to conceptualize and treat obesity as a chronic medical condition, we examined obesity-related knowledge and practices among military and civilian primary care physicians. Results were similar across these two physician groups in suggesting many physicians still may be ill-prepared to manage obesity in the primary care setting. Implications for patient care and future research are discussed.     

Cigarette use among two cohorts of U.S. Air Force recruits, compared with secular trends

This study provides a comparison of cigarette smoking among two cohorts of U.S. Air Force recruits. The first cohort, Air Force 1, entered the military between August 1995 and August 1996. The second cohort, Air Force 2, entered between October 1999 and September 2000. Cigarette use significantly increased among both men (7.0-percentage point increase) and women (7.3-percentage point increase) between the two cohorts. This difference remained statistically significant in models adjusted for demographic differences between the two groups of recruits. Direct standardization methods were then used to compare rates in both Air Force surveys with rates of current smoking reported for a national sample from the Behavioral Risk Factor Surveillance System surveys from the same years. Although the average number of cigarettes smoked and years of smoking decreased between the two cohorts, troops from Air Force 2 reported being less motivated to quit. This study suggests that efforts to reduce smoking among junior enlisted troops in the Air Force should be bolstered.     

Relationship between patterns of alcohol use and negative alcohol-related outcomes among U.S. Air Force recruits

The negative impact of alcohol use on workplace performance is of significant concern to the U.S. military, given the costs associated with recruiting, hiring, and training personnel. However, little is known about the extent of potential alcohol use problems of recruits. We examined the history of alcohol-related problems among recruits entering the Air Force (N=37858). Although the average age of recruits was <21 years, 78% reported consuming alcohol and 49% reported binging before basic military training. Recruits who drank reported having negative alcohol-related outcomes (NAROs). In fact, >95% reported that they or someone else had been injured as a result of their drinking and that a relative, friend, doctor, or other health care worker has been concerned about their drinking. The remaining NAROs were reported by approximately one-quarter of those who drank. However, recruits who reported binge drinking were substantially more likely to report more NAROs, such as morning drinking, inability to stop drinking, having others be concerned about their drinking, having blackouts, fighting, having injured or been injured, feeling guilty about their drinking, and wanting to reduce the amount they drink. Results suggest that alcohol-related problems are common among recruits before basic military training and screening for future problems may be beneficial.     

The role of preexisting pathology in the development of neointimal hyperplasia in coronary artery bypass grafts

OBJECTIVE: Saphenous vein grafts (SVG) used for coronary artery bypass surgery (CABG) often develop a gradual luminal narrowing over the first year due to neointimal hyperplasia (NH). Although the basic science of NH is well studied, our clinical understanding of this issue is limited. The purpose of this cohort study was to investigate clinical risk factors for NH by monitoring luminal narrowing within SVG using multichannel CT angiography (CTA). METHODS: Thirty patients underwent CABG involving SVG (N = 44) and arterial grafts (N = 36). Patient variables were recorded and the baseline quality of each conduit determined intraoperatively by analyzing surplus segments for intima-media thickness ratio (IMT) by histology and matrix metalloproteinase-2 by enzyme-linked immunosorbent assay. Percent luminal narrowing (%LN) was calculated for each patent graft by comparing the CTA appearance on day 5 to a repeat study at 1 y. RESULTS: Compared with arterial grafts, SVG showed significantly higher IMT at baseline (0.9 +/- 0.65 versus 0.22 +/- 0.17, P < 0.0001) and more %LN over the first year (6.9 +/- 7.5 versus 25.3 +/- 13.3% LN, P< 0.0001). Of all of the measured variables, the only significant predictors of %LN included baseline IMT (r = 0.58, P = 0.002) and matrix metalloproteinase-2 levels (r = 0.60, P = 0.002) in SVG. CONCLUSIONS: The degree of NH at baseline, a phenomenon exclusive to SVG and not found in arterial grafts, was significantly related to the development of lumen loss in the conduit over the first year after CABG. The study of SVG using serial CTA may provide unique insights into the natural history of SVG remodeling and to identify factors that influence the long-term function of this conduit.     

3��,4��-Dihydroxyflavonol down-regulates monocyte chemoattractant protein-1 in smooth muscle: role of focal adhesion kinase and PDGF receptor signalling

Background and purpose:

We investigated the effects of a synthetic flavonol, 3′,4′-dihydroxyflavonol (DiOHF) on the expression of monocyte chemoattractant protein-1 (MCP-1) in rat vascular smooth muscle cells.

Experimental approach:

MCP-1 expression was assessed by quantitative real-time PCR and protein phosphorylation by immunoprecipitation and Western blots.

Key results:

DiOHF (1–30 µmol·L⁻¹) concentration-dependently reduced MCP-1 expression in both quiescent cells and cells stimulated with platelet-derived growth factor (PDGF) or interleukin 1-β. The effect of DiOHF was associated with a suppression of focal adhesion kinase (FAK)-mediated signalling. In vitro kinase assays demonstrated that DiOHF is a potent inhibitor of FAK kinase activity (EC₅₀= 2.4 µmol·L⁻¹). Expression of FAK-related non-kinase reduced basal MCP-1 expression, but not that induced by PDGF or interleukin 1-β. DiOHF also inhibited autophosphorylation of PDGF receptors. The PDGF receptor inhibitor AG-1296 potently suppressed basal and PDGF-induced MCP-1 expression. Inhibition of extracellular signal-regulated kinase activation by DiOHF, either directly or indirectly, may also be involved in its effects on MCP-1 expression. DiOHF had no inhibitory effect on either p38 or nuclear factor-κB activation. Moreover, DiOHF inhibited smooth muscle cell spreading (a FAK-mediated response) and proliferation.

Conclusions and implications:

This is the first report on a flavonoid compound (DiOHF) that is a potent FAK inhibitor. DiOHF also inhibits PDGF receptor autophosphorylation. These effects underlie the inhibitory action of DiOHF on MCP-1 expression in smooth muscle cells. Our results suggest that DiOHF might be a useful tool for dissection of the (patho)physiological roles of FAK signalling.British Journal of Pharmacology (2009) 157, 597–606; doi:10.1111/j.1476-5381.2009.00199.x; published online 9 April 2009