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Don C Rockey

Publications and source records attributed to Don C Rockey.

At least 19 recordsLinked to original sources
PubMed2007

The effect of a low-carbohydrate, ketogenic diet on nonalcoholic fatty liver disease: a pilot study.

Nonalcoholic fatty liver disease is an increasingly common condition that may progress to hepatic cirrhosis. This pilot study evaluated the effects of a low-carbohydrate, ketogenic diet on obesity-associated fatty liver disease. Five patients with a mean body mass index of 36.4 kg/m(2) and biopsy evidence of fatty liver disease were instructed to follow the diet (<20 g/d of carbohydrate) with nutritional supplementation for 6 months. Patients returned for group meetings biweekly for 3 months, then monthly for the second 3 months. The mean weight change was -12.8 kg (range 0 to -25.9 kg). Four of 5 posttreatment liver biopsies showed histologic improvements in steatosis (P=.02) inflammatory grade (P=.02), and fibrosis (P=.07). Six months of a low-carbohydrate, ketogenic diet led to significant weight loss and histologic improvement of fatty liver disease. Further research is into this approach is warranted.

Adult↗
PubMed2007

Hepatic fibrosis 2006: report of the Third AASLD Single Topic Conference.

The Third American Associated for the Study of Liver Diseases (AASLD)-sponsored Single Topic Conference on hepatic fibrosis was held in June 2006. The conference was both international, with 6 countries represented, and cross-disciplinary, linking the basic molecular and cellular biology of fibrogenic cells to clinical trial design for emerging antifibrotic therapies. The specific goals of the conference were: (1) to consolidate knowledge about the natural history of fibrosis; (2) to clarify potential endpoints and markers; (3) to emphasize new antifibrotic targets developed on the basis of advances in basic science; and (4) to understand current critical issues pertaining to clinical trial design. Given the tremendous growth of the field and the constraints of a 2-day format, the selection of speakers was a challenge. A number of topics not included in the oral presentations were featured at poster sessions, lending breadth and depth to the meeting as a whole. Surprising new themes emerged about molecular, clinical, and regulatory aspects of the field, and a consensus emerged that hepatic fibrosis has matured into an integrated discipline that promises to significantly improve the prognosis of patients with fibrosing liver disease.

Animals↗
PubMed2006

Regulation of peroxisome proliferator-activated receptor-gamma in liver fibrosis.

The peroxisome proliferator-activated receptors (PPARs) impart diverse cellular effects in biological systems. Because stellate cell activation during liver injury is associated with declining PPARgamma expression, we hypothesized that its expression is critical in stellate cell-mediated fibrogenesis. We therefore modulated its expression during liver injury in vivo. PPARgamma was depleted in rat livers by using an adenovirus-Cre recombinase system. PPARgamma was overexpressed by using an additional adenoviral vector (AdPPARgamma). Bile duct ligation was utilized to induce stellate cell activation and liver fibrosis in vivo; phenotypic effects (collagen I, smooth muscle alpha-actin, hydroxyproline content, etc.) were measured. PPARgamma mRNA levels decreased fivefold and PPARgamma protein was undetectable in stellate cells after culture-induced activation. During activation in vivo, collagen accumulation, assessed histomorphometrically and by hydroxyproline content, was significantly increased after PPARgamma depletion compared with controls (1.28 +/- 0.14 vs. 1.89 +/- 0.21 mg/g liver tissue, P < 0.03). In isolated stellate cells, AdPPARgamma overexpression resulted in significantly increased adiponectin mRNA expression and decreased collagen I and smooth muscle alpha-actin mRNA expression compared with controls. During in vivo fibrogenesis, rat livers exposed to AdPPARgamma had significantly less fibrosis than controls. Collagen I and smooth muscle alpha-actin mRNA expression were significantly reduced in AdPPARgamma-infected rats compared with controls (P < 0.05, n = 10). PPARgamma-deficient mice exhibited enhanced fibrogenesis after liver injury, whereas PPARgamma receptor overexpression in vivo attenuated stellate cell activation and fibrosis. The data highlight a critical role for PPARgamma during in vivo fibrogenesis and emphasize the importance of the PPARgamma pathway in stellate cells during liver injury.

Adenoviridae↗
PubMed2006

The role of integrin-linked kinase in liver wound healing.

Liver wound healing is an integrated process in which hepatic stellate cells play a major role. We hypothesized that the cellextracellular signaling protein integrin-linked kinase (ILK) is important in transducing signals from the extracellular matrix to stellate cells and thus plays a critical role in stellate cell activation and fibrogenesis during liver injury. Liver injury and subsequent stellate cell activation led to a 3-fold increase in ILK expression and increased kinase activity. Overexpression of ILK in isolated stellate cells led to enhanced motility and adhesion as well as increases in smooth muscle alpha-actin and type I collagen mRNA expression. The effects of ILK on stellate cell phenotypes were phosphatidylinositol 3-kinase-dependent. Forced expression of ILK in vivo led to increases in type I collagen, smooth muscle alpha-actin, transforming growth factor-beta, and extra domain A (EDA) fibronectin mRNAs (by 3.2-, 3.5-, 2.5-, and 2.2-fold, respectively; n = 8, p < 0.05 for each versus the control), whereas inhibition of ILK in vivo led to significant reductions in these mRNAs. Morphometric analysis revealed that ILK overexpression led to a 31.4% increase in liver collagen content (n = 8, p < 0.05 versus the control); in contrast ILK knockdown in vivo led to a significant reduction in fibrogenesis. We conclude that ILK plays an important pathophysiological role in vivo in liver wound healing.

Animals↗
PubMed2006

Causes of errors in polyp detection at air-contrast barium enema examination.

PURPOSE: To retrospectively determine the cause of errors in air-contrast barium enema (ACBE) examination for detection of polyps 6 mm or larger. MATERIALS AND METHODS: The study had institutional review board approval. Informed consent was waived for this HIPAA-compliant study. ABCE findings in 41 subjects with 56 missed polyps were evaluated by two radiologists to determine if the cause of errors was perceptual or technical. A comparison was made between total number of polyps in the proximal and distal colon and those missed at each location (Fisher exact test). The 288 ACBE examinations were assessed on a scale of 0-4 (0, excellent; 4, very poor) for six colonic segments (paired t test). RESULTS: Of 17 polyps 1 cm or larger not detected in 15 subjects, 11 (65%) were missed because of technical errors and six (35%) because of perceptual errors. Eight (72%) technical and four (67%) perceptual errors occurred proximal to the splenic flexure. One 3.5-cm cecal carcinoma was not diagnosed prospectively (perceptual error). Of 39 6-9-mm polyps not detected in 26 subjects, 35 (90%) were missed because of technical errors and four (10%) because of perceptual errors. Eighty percent of technical and 75% of perceptual errors were in the proximal colon. When the proportion of polyps in the proximal and distal colon was compared, 22 (63%) of 35 polyps in the distal colon and 15 (26%) of 58 in the proximal colon were detected (P = .0009). There were no detectable differences in the quality of studies in subjects whose polyps were detected and subjects whose polyps were missed (P > .05). CONCLUSION: Technical errors were more common than perceptual errors. The majority of missed polyps were in the proximal colon. Detection rates of polypoid lesions might increase if the quality of ACBE examination can be improved, especially in the proximal colon.

Adult↗
PubMed2006

Noninvasive measures of liver fibrosis.

As novel therapies for liver fibrosis evolve, non-invasive measurement of liver fibrosis will be required to help manage patients with chronic liver disease. Although liver biopsy is the current and time-honored gold standard for measurement of liver fibrosis, it is poorly suited to frequent monitoring because of its expense and morbidity, and its accuracy suffers from sampling variation. At the current writing, serum markers and imaging methods are available and increasingly in use as alternatives to biopsy. However, many questions remain about their indications, accuracy, and cost-effectiveness, and more investigation is required before they are put into widespread use. The development of safe, inexpensive, and reliable noninvasive fibrosis measurement tools remains a research priority in clinical hepatology.

Biomarkers↗
PubMed2006

Pharmacologic therapy for gastrointestinal bleeding due to portal hypertension and esophageal varices.

Cirrhosis results in portal hypertension in many patients. The major complications of portal hypertension include development of ascites and esophageal or gastric varices. Varices lead to hemorrhage and death in a significant proportion of patients. This review focuses on the pharmacologic approach to management of portal hypertension in patients at risk of variceal hemorrhage, or those who have already had variceal bleeding. Pharmacologic therapy is used for 1) primary prevention of bleeding, 2) management of acute bleeding, and 3) prevention of recurrent bleeding (secondary prophylaxis). For acute esophageal variceal hemorrhage, a variety of pharmacologic agents are used, including somatostatin, octreotide, vapreotide, lanreotide, terlipressin, and vasopressin (with nitrates). For primary and secondary prevention of esophageal variceal hemorrhage, beta-blockers remain the mainstay therapy.

Adrenergic beta-Antagonists↗
PubMed2006

Prospective comparison of patient experience with colon imaging tests.

PURPOSE: Patient experience varies with the currently available colon imaging tests, including air contrast barium enema, computed tomographic colonography, and colonoscopy. We examined differences in patient experience with colon imaging tests and whether they varied with gender, age, and race. SUBJECTS AND METHODS: Patients with fecal occult blood, hematochezia, iron-deficiency anemia, or a family history of colon cancer underwent air contrast barium enema followed 7 to 14 days later by computed tomographic colonography and colonoscopy. Validated patient experience questionnaires that measured the experience for each test and a separate questionnaire that obtained an overall summary measure were administered after testing. Eleven patient experiences including pain, embarrassment, difficulty with bowel preparation, and satisfaction with tests were examined. RESULTS: A total of 614 subjects completed all 3 imaging tests. The test most patients were willing to repeat was colonoscopy; it also was reported to be the least painful procedure. Patients were least satisfied with air contrast barium enema, and fewer would undergo air contrast barium enema compared with computed tomographic colonography or colonoscopy. There were limited racial and gender differences in perceptions of the tests. Younger adults perceived air contrast barium enema to be more painful than older adults. CONCLUSION: Taking into account a wide variety of patient experience measures, patients preferred colonoscopy to air contrast barium enema and computed tomographic colonography. This finding has important implications for physicians considering different colon imaging tests.

Barium Sulfate↗
PubMed2006

Hepatic fibrosis, stellate cells, and portal hypertension.

Hepatic fibrogenesis is the common result of injury to the liver. It is believed to be a critical factor that leads to hepatic dysfunction and may be important in portal hypertension. The fibrogenic response is a complex process in which accumulation of extracellular matrix proteins, tissue contraction, and alteration in blood flow are prominent. A critical event in fibrogenesis is activation of resident perisinusoidal cells that are termed "hepatic stellate cells". Stellate cell activation is characterized by many important phenotypes, including enhanced extracellular matrix synthesis and prominent contractility. Given the central role of stellate cell activation in hepatic fibrogenesis (and portal hypertension), effective therapy for hepatic fibrogenesis is most likely will be directed at this event.

Collagen↗
PubMed2006

New therapies in hepatitis C virus and chronic liver disease: antifibrotics.

Fibrotic liver disease occurs after any of the various forms of injury to the liver. Fibrosis is a critical factor leading to hepatic dysfunction and portal hypertension and its complications. The fibrogenic cascade is complex but leads to accumulation of extracellular matrix proteins, followed by nodular fibrosis, tissue contraction, and alteration in blood flow. A critical concept emerging is that activation of effector cells, which produce extracellular matrix, underlies the fibrogenic process. The aggregate data has not only helped lead to an understanding of the pathophysiologic basis of hepatic fibrogenesis, but it has also provided an important context with which to base novel antifibrotic therapy.

Colchicine↗
PubMed2006

Comparison of radiologists and technologists in the performance of air-contrast barium enemas.

OBJECTIVE: The purpose of this study was to determine whether the rate of polyp detection and the quality of air-contrast barium enema (ACBE) procedures performed by technologists differ from those performed by radiologists. CONCLUSION: Our results showed that well-trained certified technologists can perform ACBE similar in overall quality and accuracy to ACBE performed by attending physicians and residents. Training technologists to perform ACBE may help to alleviate the radiology staffing shortage in the United States.

Air↗
PubMed2005

A crucial role for GRK2 in regulation of endothelial cell nitric oxide synthase function in portal hypertension.

Nitric oxide (NO) production by endothelial cell nitric oxide synthase (eNOS) in sinusoidal endothelial cells is reduced in the injured liver and leads to intrahepatic portal hypertension. We sought to understand the mechanism underlying defective eNOS function. Phosphorylation of the serine-threonine kinase Akt, which activates eNOS, was substantially reduced in sinusoidal endothelial cells from injured livers. Overexpression of Akt in vivo restored phosphorylation of Akt and production of NO and reduced portal pressure in portal hypertensive rats. We found that Akt physically interacts with G-protein-coupled receptor kinase-2 (GRK2), and that this interaction inhibits Akt activity. Furthermore, GRK2 expression increased in sinusoidal endothelial cells from portal hypertensive rats and knockdown of GRK2 restored Akt phosphorylation and NO production, and normalized portal pressure. Finally, after liver injury, GRK2-deficient mice developed less severe portal hypertension than control mice. Thus, an important mechanism underlying impaired activity of eNOS in injured sinusoidal endothelial cells is defective phosphorylation of Akt caused by overexpression of GRK2 after injury.

Animals↗