Effect of interferon-gamma on hepatic fibrosis in chronic hepatitis B virus infection: a randomized controlled study.

BACKGROUND & AIMS: Hepatic fibrosis due to chronic HBV infection has enormous socioeconomic impact. Besides strategies targeting virus elimination, prevention or reversal of liver fibrosis is amenable. Given the antifibrotic activity of interferon-gamma (IFN-gamma), a randomized open-labeled multicenter trial was initiated to test IFN-gamma in HBV infection. METHODS: HBsAg-positive patients with biopsy proven hepatic fibrosis (n = 99, stages 2-4, Scheuer criterion) were treated with diammone-glycyrrhizinate and potassium-magnesium aspartate. Sixty-six randomly assigned patients were treated with 50 mug IFN-gamma intramuscularly on a daily basis for 3 months and on alternate days the subsequent 6 months. Efficacy was evaluated by liver biopsy and serologic markers. RESULTS: Fifty-four patients in the IFN-gamma group and 29 patients in the control group completed the study. The hepatic fibrosis score was significantly reduced in 63% of IFN-gamma treated patients compared with 24.1% in the control group by using a semiquantitative scoring system evaluating both liver architecture and fibrotic deposits. Mean values for the total fibrosis score decreased from 13.8 +/- 5.8 to 10.1 +/- 5.1 in the IFN-gamma group (P = .0001), whereas they were unchanged in control subjects (13.2 +/- 6.8 vs 12.6 +/- 4.8, P = .937). The Scheuer system showed 12 out of 54 patients improved >or=1 stage(s) in the IFN-gamma group compared with 1 of 29 in the control group. Antifibrotic activity might be attributed to decreased transforming growth factor-beta signaling via phosphorylated Smad2 and reduced number of activated, alpha-smooth muscle actin positive hepatic stellate cells. CONCLUSIONS: IFN-gamma treatment for 9 months improves fibrosis scores in patients with chronic HBV infection most likely by antagonizing profibrogenic transforming growth factor-beta effects.     

Pulmonary hypertension: new perspectives

The World Health Organization symposium offers a new treatment-oriented classification of pulmonary hypertension based on an improved understanding of its pathophysiology. Regardless of the etiology, severe or unrelieved pulmonary hypertension leads to right heart failure. Symptoms and signs of pulmonary hypertension are often subtle and nonspecific. As a result, a significant delay between the onset of symptoms and the diagnosis of pulmonary hypertension is common. Echocardiography with Doppler flow is the most useful study to evaluate patients suspected of having pulmonary hypertension. The suspected diagnosis of pulmonary hypertension should then be confirmed by right heart catheterization. If present, further evaluation may include oxygen assessment, pulmonary function testing, high resolution computed tomography of the chest, and ventilation-perfusion lung scanning. Treatment of pulmonary hypertension requires uncommon expertise. General measures include correction of the underlying cause, reversal of hypoxemia and judicious use of diuretics. Advances in vasodilator therapy have increased treatment options beyond calcium channel blockers and intravenous epoprostenol. Lung transplantation remains an option for select patients with pulmonary hypertension not responding to medical management.     

Historical development of ornithophily in the western North American flora.

The 129 ornithophilous plant species in western North America have floristic affinities with one or the other of four geofloras: the Arcto-Tertiary flora (101 species), Madro-Tertiary flora (19 species), Madrean-Tethyan flora (8 species), and Neotropical flora (1 species). The last three floras have been in continuous contact with hummingbirds since some time early in the Tertiary, and ornithophily is old in this subset of western ornithophilous plants. The Arcto-Tertiary flora had no contact with hummingbirds in Eurasia or in its early history in North America. Ornithophily is a new condition in Arcto-Tertiary plant groups, dating from the first significant contact of these plants with hummingbirds in the Eocene. Buildup of the hummingbird pollination system in the Arcto-Tertiary flora is expected to be gradual and stepwise for several reasons. Ornithophilous plant groups with Arcto-Tertiary affinities in the modern western flora form a graded series with respect to taxonomic rank, taxonomic size, and ecological diversity. The series consists of one large genus (Castilleja), three small genera (Zauschneria, etc.), species groups in several genera (Penstemon, Aquilegia, etc.), single ornithophilous species in otherwise nonornithophilous genera (seven genera--e.g., Pedicularis, Monardella), and ornithophilous races in otherwise nonornithophilous species (known in two species). It is suggested that the gradations in size of the groups approximately reflect stages in their development, with the largest ornithophilous genus being oldest, with single ornithophilous species being relatively recent, and with ornithophilous races being most recent. The observed distribution of numbers of ornithophilous species among genera is in agreement with the expectation of a gradual and stepwise development of ornithophily.     

Spatial distribution of mosquito larvae and the potential for targeted larval control in The Gambia

We examined the distribution of aquatic stages of malaria vectors in a 400-km(2) area in rural Gambia to assess the practicality of targeting larval control. During the rainy season, the peak period of malaria transmission, breeding sites were 70% more likely to have anopheline larvae in the floodplain of the Gambia River than upland sites (P < 0.001). However, mosquitoes were found in some examples of all habitats, apart from moving water. Habitats most often colonized by anopheline larvae were the largest water bodies, situated near the landward edge of the flood-plain, where culicine larvae were present. In the wet season, 49% of sites had anophelines versus 19% in the dry season (P < 0.001). Larval control targeted at specific habitats is unlikely to be successful in this setting. Nonetheless, larval control initiated at the end of the dry season and run throughout the rainy season could help reduce transmission.     

Clopidogrel administration prior to coronary artery bypass grafting surgery: the cardiologist's panacea or the surgeon's headache?

AIMS: Thrombotic complications after percutaneous coronary intervention procedures have decreased in past years mainly due to the use of clopidogrel antiplatelet therapy. However, the risk of bleeding due to enhanced and irreversible platelet inhibition in patients who will require surgical coronary revascularization instead has not been adequately addressed in the literature. The purpose of this study was to evaluate the effect of pre-operative clopidrogel exposure in haemorrhage-related re-exploration rates, peri-operative transfusion requirements, morbidity, and mortality in patients undergoing coronary artery bypass grafting (CABG) surgery. METHODS AND RESULTS: A study population of 2359 patients undergoing isolated CABG between January 2000 and June 2002 was reviewed. Of these, 415 (17.6%) received clopidogrel prior to CABG surgery, and 1944 (82.4%) did not. A risk-adjusted logistic regression analysis was used to assess the association between clopidogrel pre-medication (vs. no) and haemostatic re-operation, intraoperative and post-operative blood transfusion rates, and multiple transfusions received. Haemorrhage-related pre-operative risk factors identified from the literature and those found significant in a univariate model were used. Furthermore, a sub-cohort, matched-pair by propensity scores analysis, was also conducted. The clopidogrel group had a higher likelihood of haemostatic re-operation [OR = 4.9, (95% CI, 2.63-8.97), P < 0.01], an increase in total packed red blood cell transfusions [OR = 2.2, (95% CI, 1.70-2.84), P < 0.01], multiple unit blood transfusions [OR = 1.9, (95% CI, 1.33-2.75), P < 0.01] and platelet transfusions [OR = 2.6, (95% CI, 1.95-3.56), P < 0.01]. Surgical outcomes and operative mortality [OR = 1.5, (95% CI, 0.36-6.51), P = 0.56] were not significantly different. CONCLUSION: Pre-operative clopidogrel exposure increases the risk of haemostatic re-operation and the requirements for blood and blood product transfusion during, and after, CABG surgery.     

The future of proteomics in the study of alcoholism

This article represents the proceedings of a workshop at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The workshop organizers/chairpersons were Chinnaswamy Kasinathan and Paul Manowitz. The presentations were (1) Introduction to the field of proteomics, by Kent Vrana; (2) Use of proteomics in the identification of urinary biomarkers for alcohol intake, by Chinnaswamy Kasinathan, Paul Thomas, and Paul Manowitz; (3) Proteomics screening illuminates ethanol-mediated induction of HDL proteins in macaques, by Kent Vrana, Randy Gooch, Travis Worst, Stephen Walker, Aaron Xu, Peter Pierre, Heather Green, and Kathleen Grant; and (4) Proteomics applied to the study of the liver, by Laura Beretta.     

Defining Optimal Self-Management in Osteoarthritis: Racial Differences in a Population-Based Sample

The aim of this study was to examine optimal self-management in osteoarthritis and its association with patient-reported outcomes. We recruited a population-based sample of Medicare beneficiaries (n = 551) residing in Allegheny County, PA, USA and elicited an expanded set of self-management behaviors using open-ended inquiry. We defined optimal self-management according to clinical recommendations, including use of hot compresses on affected joints, alteration of activity, and exercise. Only 20% practiced optimal self-management as defined by two or more of these criteria. Optimal and suboptimal self-managers did not differ in sociodemographic features. Both white and African–Americans who practiced optimal self-management reported significantly less pain, but the benefit was greatest in severe disease for whites and for mild-moderate disease among African–Americans. This backdrop of naturally occurring self-management behaviors may be important to recognize in planning programs that seek to bolster self-management skills.     

Effect of acupuncture on gastric acid secretion in healthy male volunteers

Six randomized, placebo controlled studies were performed to investigate the effect of electroacupuncture on gastric acid output in 38 healthy males. Electroacupuncture decreased basal acid output when compared to placebo acupuncture [from 3.50±0.59 mmol/hr to 2.54±0.56 mmol/hr (P<0.05)] as well as sham feeding-stimulated acid output [from 18.52±2.25 mmol/hr to 5.38±2.11 mmol/hr (P<0.005)], but had no effect on the pentagastrin stimulated acid output. The inhibitory effect of acupuncture on sham feeding-stimulated acid output was not affected by local anesthesia of the acupoint, but was prevented by a prior intravenous naloxone injection. Acupuncture did not alter plasma gastrin levels (20.7±7.6 g/liter, vs control 21.2±7.2 g/liter) but naloxone increased it (26.1±14.5 g/liter) (P<0.05). We conclude that the antisecretory effects of electroacupuncture do not result from decreased gastrin release or decreased parietal cell sensitivity to gastrin, but are mediated through naloxone-sensitive opioid neural pathways and vagal efferent pathways.Dr. Tougas was supported by a Fellowship of the Medical Research Council of Canada.This work was presented in part at the Annual Meeting of The American Gastroenterological Association, New Orleans, May 1988; Washington, May 1989; and San Antonio, May 1990.