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D C Rockey

Publications and source records attributed to D C Rockey.

At least 19 recordsLinked to original sources
PubMed2006

Interferon gamma-1b for the treatment of fibrosis in chronic hepatitis C infection.

Given that the complications of hepatitis C are due to fibrosis, we hypothesized that the antifibrotic effects of interferon gamma on stellate cells would lead to beneficial effects in patients with hepatitis C. Thus, we evaluated the safety and efficacy of interferon gamma-1b in patients with hepatitis C. A cohort of 20 patients with chronic hepatitis C who failed or were intolerant to previous interferon-alpha-based regimens received 200 mug of interferon gamma-1b subcutaneously three times weekly for 24 weeks. Liver biopsy was performed prior to and at the end of treatment. Biopsies were evaluated by a single blinded pathologist using the Knodell system modified by Ishak, and fibrosis was also quantitated by morphometric analysis. The study population was 75% male and 70% Caucasian. Mean age was 47.9 +/- 7.5 years. Eighteen of 20 patients completed therapy. One patient discontinued therapy because of constitutional symptoms. One patient discontinued therapy because of elevated aminotransferases greater than twice baseline. No serious adverse events occurred. Morphometric analysis revealed that six patients (30%) had >1% absolute reduction in fibrosis score. Four of 20 (20%) patients had improvement in Ishak fibrosis scores after treatment. In conclusion, interferon gamma therapy is safe and well tolerated in patients with chronic hepatitis C. Although we did not detect an overall reduction in fibrosis, interferon gamma-1b treatment led to a reduction in fibrosis in selected patients. These data provide a basis for further study of interferon gamma-1b in patients with chronic fibrosing liver disease.

Antiviral Agents↗
PubMed2003

Systematic review: terlipressin in acute oesophageal variceal haemorrhage.

BACKGROUND: Controversy exists surrounding pharmacological therapy in acute variceal bleeding. AIM: To determine the efficacy and safety of terlipressin. METHODS: Randomized trials were identified and duplicate, independent, review identified 20 randomized trials involving 1609 patients that compared terlipressin with placebo, balloon tamponade, endoscopic treatment, octreotide, somatostatin or vasopressin for treatment of acute oesophageal variceal haemorrhage. RESULTS: Meta-analysis showed that compared to placebo, terlipressin reduced mortality (relative risk 0.66, 95% CI 0.49-0.88), failure of haemostasis (relative risk 0.63, 95% CI 0.45-0.89) and the number of emergency procedures per patient required for uncontrolled bleeding or rebleeding (relative risk 0.72, 95% CI 0.55-0.93). When used as an adjuvant to endoscopic sclerotherapy, terlipressin reduced failure of haemostasis (relative risk 0.75, 95% CI 0.58-0.96), and had an effect on reducing mortality that approached statistical significance (relative risk 0.74, 95% CI 0.53-1.04). No significant difference was demonstrated between terlipressin and endoscopic sclerotherapy, balloon tamponade, somatostatin or vasopressin. Haemostasis was achieved more frequently with octreotide compared to terlipressin (relative risk 1.62, 95% CI 1.05-2.50), but this result was based on unblinded studies. Adverse events were similar between terlipressin and the other comparison groups except for vasopressin, which caused more withdrawals due to adverse events. CONCLUSIONS: Terlipressin is a safe and effective treatment for acute oesophageal variceal bleeding, with or without adjuvant endoscopic sclerotherapy. Terlipressin appears to reduce mortality in acute oesophageal variceal bleeding compared to placebo, and is the only pharmacological agent shown to do so. Future studies will be required to detect potential mortality differences between terlipressin and other therapeutic approaches.

Esophageal and Gastric Varices↗
PubMed2001

Terlipressin for acute esophageal variceal hemorrhage.

BACKGROUND: Terlipressin (triglycyl lysine vasopressin) is a synthetic analogue of vasopressin, which has been used in the treatment of acute variceal hemorrhage. In contrast to vasopressin, terlipressin can be administered as intermittent injections instead of continuous intravenous infusion and it has a safer adverse reactions profile. However, its effectiveness remains uncertain. OBJECTIVES: To determine if treatment with terlipressin improves outcome in acute esophageal variceal hemorrhage and is safe. SEARCH STRATEGY: Randomized clinical trials were identified by searching the following databases: MEDLINE, EMBASE, the Cochrane Controlled Trials Register, the Cochrane Hepato-Biliary Group Controlled Trials Register, Biosis, and Current Contents. The bibliographies of identified publications were checked. Experts in the field and the manufacturers of terlipressin were contacted. SELECTION CRITERIA: All randomized clinical trials which compared terlipressin with: (a) placebo or no treatment, (b) balloon tamponade, (c) endoscopic treatment, (d) octreotide, (e) somatostatin and (f) vasopressin, in the setting of acute variceal hemorrhage. DATA COLLECTION AND ANALYSIS: Eligibility, trial quality assessment and data extraction were done independently by two reviewers. The primary outcome measure was mortality. Secondary outcomes were failure of initial hemostasis, rebleeding, procedures required for uncontrolled bleeding or rebleeding, transfusion requirements and length of hospitalization. MAIN RESULTS: Twenty studies were identified for all the comparison groups, involving 1609 patients. There were seven studies (with 443 patients) comparing terlipressin to placebo, five of which were considered to be high quality studies based on the Jadad scale. The meta-analysis indicates that terlipressin was associated with a statistically significant reduction in all cause mortality compared to placebo (relative risk 0.66, 95% confidence interval 0.49 to 0.88). Three studies (with 302 patients) were identified comparing terlipressin to somatostatin, two of which were high quality studies; only one high quality study (219 patients) comparing terlipressin to endoscopic treatment was identified. Within the limited power provided by these small numbers of patients, no statistically significant difference was demonstrated between terlipressin and either somatostatin or endoscopic treatment in any of the outcomes. For the remaining comparison groups (terlipressin versus balloon tamponade, terlipressin versus octreotide and terlipressin versus vasopressin) only small, low quality studies were identified and no difference was demonstrated in any of the major outcomes. There was no difference between the terlipressin group and any of the comparison groups in the number of adverse events that caused death or withdrawal of medication. REVIEWER'S CONCLUSIONS: On the basis of a 34% relative risk reduction in mortality, terlipressin should be considered to be effective in the treatment of acute variceal hemorrhage. Further, since no other vasoactive agent has been shown to reduce mortality in single studies or meta-analyses, terlipressin might be the vasoactive agent of choice in acute variceal bleeding.

Acute Disease↗
PubMed2001

Cellular pathophysiology of portal hypertension and prospects for management with gene therapy.

In summary, regulation of sinusoidal blood flow in normal and injured liver involves structural, cellular, and humoral components. Available data suggest that stellate cells, resident perisinusoidal mesenchymal cells with a histologic orientation in the sinusoid analogous to [figure: see text] vasoregulatory pericytes, modulate sinusoidal blood flow. This regulation by stellate cells is most evident in the context of liver injury but may apply also to the normal liver. The endothelin and NO systems are important in modulating stellate cell contractility, and their degree of equilibrium is significant in determining the level of local intrahepatic resistance, especially in the injured liver. Manipulation of either or both of these systems is feasible and effective in experimental models. Such findings have obvious clinical implications and are expected to set the [figure: see text] stage for novel gene therapy approaches for treatment of patients with portal hypertension.

Endothelins↗
PubMed2001

Hepatic blood flow regulation by stellate cells in normal and injured liver.

Hepatic stellate cells have received considerable attention as key components of the fibrogenic response to injury. Beyond this feature, they also have been implicated as regulators of sinusoidal vascular tone, and in disease states, in the pathogenesis of intrahepatic portal hypertension. The basis for this latter concept is derived from the following: (a) stellate cells are situated in a perisinusoidal orientation within the sinusoid, optimized for sinusoidal constriction; (b) a series of studies performed over the past decade have demonstrated that perisinusoidal stellate cells exhibit a remarkable capacity for cellular contraction, a characteristic that is most prominent after liver injury and stellate cell activation; and (c) in vivo microscopy studies have revealed that stellate cells can mediate sinusoidal constriction. Available evidence indicates that liver injury leads to a vascular disorder in which endothelin-1 is overproduced by stellate cells and endothelial cell-derived nitric oxide production is reduced. These abnormalities, in the context of exaggerated stellate cell contractility after liver injury, set up a paradigm in which stellate cells contribute to the increased intrahepatic resistance typical of portal hypertension. Furthermore, because stellate cell contractility and the mediators that control this function are dynamic processes, strategies that target exaggerated contractility provide an opportunity for novel therapeutics in intrahepatic portal hypertension.

Cell Physiological Phenomena↗
PubMed2001

Comparison of patients' experiences during imaging tests of the colon.

BACKGROUND: Physical discomfort, anxiety, embarrassment, and other aspects of patient experience impact on future compliance for colonic imaging tests. Therefore, a prospective study was performed comparing patient experiences during air contrast barium enema (ACBE), flexible sigmoidoscopy, and colonoscopy. METHODS: Immediately after each procedure, patients completed a questionnaire assessing pretest anxiety, difficulty with preparation, pain, cramping, bloating, overall discomfort, loss of dignity, willingness to repeat the test, and overall satisfaction. A follow-up questionnaire was administered within 48 hours. Nurses and physicians also completed questionnaires to assess the provider impression of patient experience. RESULTS: Four hundred ten patients (80 ACBE, 202 sigmoidoscopy, 128 colonoscopy) were prospectively enrolled. Sigmoidoscopy caused more pain than ACBE (Odds ratio [OR] 2.64: 95% CI [1.63, 4.27]) or colonoscopy (OR 1.83: 95% CI [1.21, 2.77]). ACBE and colonoscopy did not differ in the degree of pain. Although overall satisfaction appeared to be similar for all tests, patients were less willing to repeat ACBE than sigmoidoscopy (OR 1.85: 95% CI [1.13, 3.02]) or colonoscopy (OR 1.82: 95% CI [1.07, 3.09]). Initial and follow-up pain ratings by patients were highly correlated (Spearman correlation 0.81); however, correlation of pain assessments between staff and patients was poor (Spearman correlation 0.48). CONCLUSIONS: Sigmoidoscopy was more painful than other colonic imaging modalities. Although ACBE and colonoscopy caused similar pain, patients were less willing to repeat ACBE. In aggregate, the data suggest that patients perceive colonoscopy as the most acceptable colonic imaging procedure. Better methods are required to allow staff to adequately assess discomfort experienced by patients during these procedures.

Adult↗
PubMed2001

Hepatobiliary infections.

The major hepatobiliary infections (excluding the viral hepatitides) include amebic and pyogenic liver abscess and cholangitis. Little new information has been published in the area of cholangitis during the last several years. In contrast, the clinical presentation and management of liver abscess have evolved considerably, not only in the last several years but also during a more extended period spanning the last two decades. In the United States, amebic liver abscess occurs largely in individuals from endemic areas or in those traveling to endemic areas. Recent data suggest that patients with human immunodeficiency virus (HIV) infection are at an increased incidence of amebic liver abscess. New serologic tests and molecular techniques are being added to the diagnostic armamentarium for amebic liver abscess. In most cases, amebic liver abscess is associated with an excellent prognosis (up to 100% survival) if properly managed. Pyogenic liver abscess, although commonly occurring in patients with known biliary tract disease, is often cryptogenic in origin (ie, no clear causal factor can be identified) or often is caused by underlying medical disorders. An emerging population of patients with pyogenic liver abscess includes those with complications of aggressive interventions (hepatic chemoembolization, cryoablation, liver transplantation). Pyogenic liver abscess was predominantly managed by surgical methods up until the early 1980s, but almost entirely has changed to being managed by interventional techniques; in 2000, this trend has continued. In contrast to amebic liver abscess, pyogenic liver abscess is associated with greater morbidity and mortality, ostensibly caused by the severity of the underlying disease in many patients. However, it should be emphasized that the prognosis of patients with pyogenic liver abscess, who do not have underlying comorbid conditions, is excellent.

Journal Article↗
PubMed2001

Endoscopic therapy of acute diverticular hemorrhage.

OBJECTIVE: Diverticular hemorrhage is a common cause of lower GI bleeding and can be diagnosed acutely during colonoscopy. However, whether early diagnosis leads to effective intervention remains controversial. The aim of this study was to evaluate whether urgent colonoscopic therapy is effective as acute and long term treatment for diverticular bleeding with stigmata of hemorrhage. METHODS: We reviewed the medical records of all patients who underwent endoscopic therapy for diverticular bleeding from January, 1994 to June, 2000 at Duke University Medical Center. Patients or their families were contacted to obtain complete follow-up including data on subsequent bleeding. RESULTS: We identified 13 patients who underwent colonoscopic hemostatic management for the treatment of acute diverticular bleeding. Therapy consisted of epinephrine injection and/or multipolar electrocoagulation. Five patients (38%) experienced early rebleeding, within 30 days of the index bleed, four of whom required surgery, and three patients (23%) had late rebleeding. There were no complications of endoscopic therapy. CONCLUSIONS: Endoscopic therapy can provide early hemostasis in some cases of acute diverticular hemorrhage. However, its value in preventing subsequent diverticular bleeding is unclear.

Aged↗
PubMed2000

Ischemic hepatitis: clinical presentation and pathogenesis.

BACKGROUND: The pathophysiology of ischemic hepatitis, otherwise known as "shock liver," is poorly understood, although it is believed to be the result of a reduction in systemic blood flow as typically occurs in shock. The aim of this study was to investigate the importance of this phenomenon as well as other clinical features in patients with ischemic hepatitis. METHODS: We identified a cohort of 31 patients (case group) who met the most commonly accepted definition of ischemic hepatitis (an acute reversible elevation in either the serum alanine or aspartate aminotransferase level of at least 20 times the upper limit of normal, excluding known causes of acute hepatitis or hepatocellular injury, in an appropriate clinical setting). We also evaluated the clinical features and serum aminotransferase levels in a cohort (the control group) of 31 previously healthy patients who sustained major nonhepatic trauma at San Francisco General Hospital, a major trauma center. Both groups of patients had documented systolic blood pressures <75 mm Hg for at least 15 minutes. Clinical and hemodynamic (invasive and noninvasive) data were recorded. RESULTS: Despite the marked reduction in blood pressure, no patient in the control group developed ischemic hepatitis. The mean (+/- SD) peak serum aspartate aminotransferase level in the control group was only 78 +/- 72 IU, in contrast with a mean peak of 2,088 +/- 2,165 IU in the case group. All 31 patients with ischemic hepatitis had evidence of underlying organic heart disease, 29 (94%) of whom had right-sided heart failure. CONCLUSIONS: Systemic hypotension or shock alone did not lead to ischemic hepatitis in any patient. The vast majority of patients with ischemic hepatitis had severe underlying cardiac disease that had often led to passive congestion of the liver. These data lead us to propose that right-sided heart failure, with resultant hepatic venous congestion, may predispose the liver to hepatic injury induced by a hypotensive event.

Acute Disease↗
PubMed2000

Expression of the integrin alpha8beta1 during pulmonary and hepatic fibrosis.

The fibrotic response after diverse forms of injury is characterized by the accumulation of extracellular matrix proteins, proliferation of myofibroblast-like cells, and organ contraction. Myofibroblasts are key effector cells in the development of the fibrotic response. They contribute to fibrosis through both increased cell number (proliferation) and enhanced matrix synthesis. Integrins, a class of cell adhesion molecules, are mediators of cell-extracellular matrix protein interactions that are important in the proliferative and migratory response of cells to matrix proteins. We have previously cloned the human integrin subunit alpha8, documented its high expression in lung tissue, and established it as a receptor for the matrix proteins fibronectin, vitronectin, and tenascin. We now demonstrate that alveolar interstitial cells are the primary cell type expressing alpha8beta1 in the lung parenchyma. Expression of alpha8beta1 is concentrated primarily along the thinned extensions of cells and at the tips of filopodia. Because of its unique distribution in alveolar interstitial cells, we hypothesized that it may play a role in the fibrotic response after injury. In bleomycin-induced pulmonary fibrosis, there is increased expression of alpha8beta1 by interstitial fibroblasts, the majority of which coexpress alpha smooth muscle actin, a marker of tissue myofibroblasts. To establish a more general role for alpha8beta1 during organ fibrosis, we further examined its expression in two rat models of liver fibrosis. During hepatic injury due to either carbon tetrachloride injury or bile duct ligation, we demonstrate de novo expression of alpha8beta1 in activated hepatic stellate cells, the myofibroblast equivalent in liver. Taken together, the data localize alpha8beta1 to myofibroblast-like cells during wound healing and suggest that signal transduction through the alpha8beta1 integrin may contribute to the fibrotic response of organs to injury.

Animals↗
PubMed2000

The cell and molecular biology of hepatic fibrogenesis. Clinical and therapeutic implications.

Much has been learned in the past 2 decades about the cellular and molecular mechanisms underlying hepatic fibrogenesis and about potential therapeutic approaches in patients with liver disease. The central event in fibrogenesis seems to be the activation of hepatic stellate cells. Stellate cell activation is characterized by several important features, including enhanced matrix synthesis and a prominent contractile phenotype, processes that probably contribute to the physical distortion and dysfunction of the liver in advanced disease. It is important to emphasize that the factors controlling activation are multifactorial and complex. The extracellular matrix is a dynamic, active constituent of the fibrogenic response and undergoes active remodeling, including synthesis and degradation. Effective therapy for hepatic fibrogenesis will probably also be multifactorial, based on the basic mechanisms underlying the fibrogenic process. The most effective therapies will probably be directed at the stellate cell. Approaches that address matrix remodeling (i.e., by enhancing matrix degradation or by inhibiting factors that prevent matrix breakdown) may be effective.

Cytokines↗
PubMed2000

Diagnosis and management of lower gastrointestinal bleeding.

There are few randomized, prospective trials evaluating the optimal diagnostic and therapeutic strategies in the management of lower gastrointestinal bleeding. However, recent data suggest that urgent colonoscopy represents a safe and effective initial diagnostic approach. The role of tagged erythrocyte scintigraphy is yet to be defined, but it may be of utility as a screening test for visceral angiography. Colonoscopy and angiography both offer substantial therapeutic options but remain of unproved benefit from a treatment standpoint; surgery continues to play an important role in the management of lower gastrointestinal bleeding. Obscure gastrointestinal bleeding, which often presents as lower gastrointestinal bleeding, continues to be one of the most challenging diagnostic and therapeutic problems in gastroenterology. Occult gastrointestinal bleeding, often arising from the lower gastrointestinal tract, usually mandates gastrointestinal evaluation.

Journal Article↗