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M F Chen

Publications and source records attributed to M F Chen.

At least 37 records · Page 2Linked to original sources

Human REG I gene is up-regulated in intrahepatic cholangiocarcinoma and its precursor lesions.

The Reg I gene (regenerating gene) and its product (Reg protein) are a regenerating and/or proliferating factor(s) of pancreatic islet cells. The ectopic expression of REG Ialpha was shown in colorectal carcinomas, suggesting that REG Ialpha is related to their carcinogenesis. In this study, we examined the expression of REG I in intrahepatic cholangiocarcinoma (ICC) and its precursor lesion (biliary dysplasia). By polymerase chain reaction and in situ hybridization (ISH) studies using a total of 16 fresh liver specimens, REG Ialpha mRNA was demonstrated in 6 of 11 (55%) ICC cases, but in 0 of 5 (0%) normal livers. Immunohistochemistry for REG I protein was performed in 100 formalin-fixed, paraffin-embedded sections obtained from the 18 cases of ICC alone, 45 hepatolithiasis with ICC (n = 19) or biliary dysplasia (n = 26), 21 hepatolithiasis alone (all with hyperplasia), and 16 normal livers. In ICC, the expression of REG I protein was significantly dependent on the histologic differentiation; 12 of 13 (92%) cases in papillary and well-differentiated, 6 of 16 (38%) cases in moderately differentiated, and 0 of 8 (0%) cases in poorly differentiated types. Moreover, in the lesions of hyperplasia, low-grade dysplasia, and high-grade dysplasia in hepatolithiasis, REG I protein was expressed in 4 of 21 (19%), 7 of 12 (58%), and 13 of 14 (93%) cases, respectively. In normal liver, intrahepatic bile ducts were constantly negative for REG I protein. These findings suggest that neoexpression of REG I is a good marker for biliary mucosa at risk for development of ICC, and also that REG I plays a role in the early stages of biliary carcinogenesis, probably via a cell-proliferative effect.

Bile Duct Neoplasms↗

Intraductal papillary neoplasia of the liver associated with hepatolithiasis.

Intraductal papillary growth of neoplastic biliary epithelia with a fine fibrovascular stalk (intraductal papillary neoplasia of liver [IPN-L]) resembling intraductal papillary mucinous neoplasm of pancreas is occasionally associated with hepatolithiasis. In this study, 136 cases of hepatolithiasis in Taiwan, between January 1998 and March 2000, and an additional 21 cases of IPN-L before December 1998, were examined histologically. IPN-L was found in 41 of 136 hepatolithiasis cases (30.1%). Sixty-two IPN-L cases (42 women and 20 men; age range, 59.8 +/- 10 years) were divided into 4 types (type 1, IPN-L with low-grade dysplasia, 23 cases; type 2, IPN-L with high grade dysplasia, 11 cases; type 3, IPN-L with in situ and microinvasive carcinoma, 13 cases; and type 4, IPN-L of types 2 and 3 with distinct invasive carcinoma, 15 cases). Intraductal spreading and glandular involvement were commonly observed in all types. About half of types 3 and 4 cases had mucobilia, and mucinous carcinoma was variably found in two thirds of group 4 patients. IPN-L frequently showed variable gastroenteric differentiation such as goblet cells and foveolar and colon-like metaplasia. IPN-L with goblet cells and colon-like metaplasia was frequently associated with overproduction of mucin and mucobilia (P <.01). In Japan, IPN-L was not frequent in hepatolithiasis (12 of 135 cases). In conclusion, IPN-L forms a spectrum of biliary neoplasm in hepatolithiasis. It often displays variable gastroenteric metaplasia and significant intraductal spread. IPN-L tends to progress to mucinous carcinoma. Formerly reported "mucin-producing intrahepatic cholangiocarcinoma" with a favorable prognosis is included in IPN-L.

Adult↗

Effective treatment of small murine hepatocellular carcinoma by dendritic cells.

Hepatocellular carcinoma (HCC) is a common malignancy with a poor prognosis. This investigation examined whether dendritic cell-based immunotherapy can treat murine HCC effectively. Bone marrow-derived dendritic cells were propagated from C57BL/10J mice in GM-CSF (4 ng/mL) and interleukin (IL)-4 (1,000 micro/mL). The dendritic cells were pulsed with a Hepa1-6 lysate overnight and employed to treat murine HCC. For in vivo study, HCC was created by inoculation of hepa1-6, 5 x 10(5) cells, in the flank of C57BL/10J mice. HCC were categorized into small (3 x 3-mm) and large (5 x 5-mm) tumors. These HCC were treated by dendritic cells intravenously, twice at weekly intervals. The results revealed that lymphocytes could be gathered around small HCC after administration of Hepa1-6 lysate-pulsed dendritic cells. Seven of 12 (58.3%) small HCC could be eradicated completely by dendritic cell-based immunotherapy, and 33.3% of the small tumors responded to immunotherapy partially which were held in a stable condition for 34.0 +/- 7.4 days before the tumors regrew. For large HCC, lymphocytes did not gather around the tumors, and the tumors cannot be eradicated effectively by dendritic cells. However, dendritic cell-based immunotherapy could slow down the growth rate of large tumors (116.2 +/- 91.4 mm(3) vs. 234.0 +/- 149.1 mm(3) of the control on day 7, P =.043; and 280.3 +/- 224.7 mm(3) vs. 870.0 +/- 418.9 mm(3) of the control on day 17, P <.001). Conclusively, dendritic cells pulsed with a Hepa1-6 lysate can be employed to treat small HCC in vivo effectively. However, the efficacy of dendritic cell-based immunotherapy decreases while tumors grow.

Animals↗

Pulmonary structural maturation and pulmonary artery remodeling after reversible fetal ovine tracheal occlusion in diaphragmatic hernia.

PURPOSE: Congenital diaphragmatic hernia (CDH) is associated with thickened pulmonary arteries (PA) contributing to pulmonary hypertension. In the current study, the effects of antenatal glucocorticoids and reversible tracheal occlusion (TO) on PA structure were assessed in a hypoplastic lung model. METHODS: A left-sided CDH was created in fetal lambs at 80 days gestation, TO at 108 days, and release of the occlusion (TR) at 129 days. All were given 1 dose of maternal glucocorticoids at 135 days. At 136 days (term, 145 days), the fetus was delivered by cesarian section. CDH (n = 7), CDH + TO (n = 6), CDH + TO + TR (n = 6), and unoperated twin controls (n = 16) were compared. Outcome measurements were (1) lung growth, represented by lung weight to body weight ratio (LW/BW), (2) lung structural maturation, which is inversely proportional to mean terminal bronchiole density (MTBD), (3) PA medial and adventitial areas (square micrometers), (4) lung capillary load, which is the ratio of vessel surface area (SA) to tissue SA ratio. RESULTS: CDH lungs were hypoplastic with a low LW/BW and high MTBD. The small PAs (<75 microm) of CDH had an increased medial area, indicating increased muscle mass and an increased adventitial area. CDH + TO +/- TR increased LW/BW and achieved normal structural lung maturity with a low MTBD. Only CDH + TO thinned the PA medial area closer to control values. The adventitial area remained thick in CDH +/- TO +/- TR when compared with controls. All 4 groups had similar capillary load. CONCLUSIONS: TO may be especially important for PA remodeling in the latter part of gestation, because TR 1 week before delivery prevents thinning of the small PAs in CDH. The shaping achieved by TO in terms of lung growth, structural maturity, and pulmonary artery medial area thinning may prove beneficial in lessening the severity of the associated pulmonary hypertension in CDH.

Animals↗

The multiple facets of pulmonary sequestration.

PURPOSE: The goal of this study was to identify the proportion of sequestrations that were atypical or associated with other entities, such as congenital cystic adenomatoid malformations, communicating bronchopulmonary foregut malformations, bronchogenic cyst, and scimitar syndrome. METHODS: All charts of patients with pulmonary sequestration admitted at 2 children's hospitals from 1982 to July 1999 were reviewed retrospectively. The authors included all anomalies with a systemic arterial supply or without bronchial connection. RESULTS: Only 22 of the 39 patients (56%) had a classic isolated extralobar or intralobar sequestration, whereas the others presented with a spectrum of anomalies. Of the 13 cases diagnosed prenatally, 85% were asymptomatic at birth. In contrast, 26 cases diagnosed postnatally were all symptomatic, with those patients less than 2 weeks old presenting with various degrees of respiratory distress, and those older than 2 weeks old presenting with respiratory infections. The correct diagnosis was made preoperatively in 59% of cases. Only 4 patients did not undergo resection of their lesion, of which, 1 underwent interventional radiology with embolization of the anomalous arterial supply. Follow-up issues of importance included pneumonia, asthma, gastroesophageal reflux, and pectus excavatum. CONCLUSIONS: Sequestrations represent a spectrum of anomalies that overlap with other lung lesions. To facilitate management, they should be described according to their (1) connection to the tracheobronchial tree, (2) visceral pleura, (3) arterial supply, (4) venous drainage, (5) foregut communication, (6) histology, (7) mixed/multiple lesions, and (8) whether there are associated anomalies. Surgeons should be aware that approximately 50% of sequestrations could be atypical or associated with other anomalies. This should be kept in mind when weighing the benefits of resection versus conservative management of pulmonary sequestrations.

Abnormalities, Multiple↗

Effect of gemfibrozil on the composition and oxidation properties of very-low-density lipoprotein and high-density lipoprotein in patients with hypertriglyceridemia.

Recent studies suggest that both oxidized very-low-density lipoprotein (VLDL) and oxidized high-density lipoprotein (HDL) may play a role in the pathogenesis of atherosclerosis. Gemfibrozil is widely used and is reported to decrease VLDL levels and increase HDL levels. The aim of this study was to investigate the effect of gemfibrozil on the chemical composition and oxidative susceptibility of VLDL and HDL and their relationship with atherosclerosis. Twenty patients with hypertriglyceridemia were treated with 300 mg gemfibrozil, 3 times daily, for 12 weeks. Venous blood samples were collected before treatment, at the end of treatment, and 4 weeks after the end of treatment. Gemfibrozil effectively lowered concentrations of plasma lipid, apolipoprotein (apo) B, and apo E. The lipid and protein content of VLDL were also decreased, but not by the same extent. The surface-to-core ratio and apo E/apo B ratio of VLDL particles were increased after gemfibrozil treatment. HDL(2) cholesteryl ester and HDL(3) apo A-II content were also increased. Gemfibrozil treatment lowered levels of lipid peroxides in both VLDL and HDL particles. The susceptibility of VLDL to oxidation was unchanged, whereas maximal peroxide production was decreased. The oxidative susceptibility of both HDL(2) and HDL(3) decreased with gemfibrozil treatment. These results indicate that after gemfibrozil treatment, VLDL and HDL particles in patients with hypertriglyceridemia are less atherogenic, which may explain why gemfibrozil treatment is beneficial in terms of coronary heart disease in hypertriglyceridemia.

Adult↗

Different fast-gate regulation by external Cl(-) and H(+) of the muscle-type ClC chloride channels.

The fast gate of the muscle-type ClC channels (ClC-0 and ClC-1) opens in response to the change of membrane potential (V). This gating process is intimately associated with the binding of external Cl(-) to the channel pore in a way that the occupancy of Cl(-) on the binding site increases the channel's open probability (P(o)). External H(+) also enhances the fast-gate opening in these channels, prompting a hypothesis that protonation of the binding site may increase the Cl(-) binding affinity, and this is possibly the underlying mechanism for the H(+) modulation. However, Cl(-) and H(+), modulate the fast-gate P(o)-V curve in different ways. Varying the external Cl(-) concentrations ([Cl(-)](o)) shifts the P(o)-V curve in parallel along the voltage axis, whereas reducing external pH mainly increases the minimal P(o) of the curve. Furthermore, H(+) modulations at saturating and nonsaturating [Cl(-)](o) are similar. Thus, the H(+) effect on the fast gating appears not to be a consequence of an increase in the Cl(-) binding affinity. We previously found that a hyperpolarization-favored opening process is important to determine the fast-gate P(o) of ClC-0 at very negative voltages. This [Cl(-)](o)-independent mechanism attracted little attention, but it appears to be the opening process that is modulated by external H(+).

Animals↗

Intra-abdominal pressure monitoring as a guideline in the nonoperative management of blunt hepatic trauma.

BACKGROUND: Nonoperative management has been validated as a standard of care for patients with blunt hepatic trauma. We herein study the correlation of intra-abdominal pressure (IAP) and other clinical parameters to predict the failure of nonoperative management, and attempt to use IAP to determine further therapeutic options. METHODS: During a 9-month period, 25 hemodynamically stable patients sustaining grades III to V blunt hepatic injuries were prospectively studied. They were admitted to the intensive care unit for clinical reevaluation, and hemodynamic and IAP monitoring. If the patient developed an IAP greater than 25 cm H(2)O, then an emergent laparotomy or laparoscopy was performed to achieve hemostasis and decompression of intra-abdominal hypertension (IAH). On the basis of an IAP of 25 cm H(2)O, the correlation between the IAP and an estimated amount of liver-related transfusion, the Pao(2)/Fio(2) ratio and peritoneal signs were analyzed. RESULTS: Of the 25 patients being studied, 20 (80%) had an IAP below 25 cm H(2)O, 1 of whom was found to have a pelvic abscess from an amputated segment of liver. On the other hand, five other patients with an IAP greater than 25 cm H(2)O received decompression and laparoscopic examinations, and one needed an open hepatorrhaphy. In general, though, 19 patients (76%) were successfully treated without operation. All recovered well after different therapeutic regimens; however, two developed liver abscesses, for a morbidity rate of 8% (2 of 25). This analysis revealed a strong association between the IAP value and the presence of peritoneal signs (Phi coefficient = 0.890, p < 0.001), but not in the estimated amount of liver-related transfusion and Pao(2)/Fio(2) ratio. CONCLUSION: This preliminary investigation suggests that IAH or abdominal compartment syndrome can develop while patients receive nonoperative management for grade III to V blunt hepatic injuries. There were no parameters that precisely reflected ongoing hepatic hemorrhage or predicted hemodynamic instability. Although the amount of hepatic hemorrhage was not accurately measured by the IAP, it could be reflected by an increased IAP. During nonoperative management, IAP monitoring may be a simple and objective guideline to suggest further intervention for patients with blunt hepatic trauma. Laparoscopic hepatic evaluation and abdominal decompression may be helpful in this situation.

Abdominal Injuries↗

Prostacyclin analogue (OP-2507) induces delayed ex vivo neutrophil apoptosis and attenuates reperfusion-induced hepatic microcirculatory derangement in rats.

Leukocyte-endothelial adherence and changes of blood flow in microcirculation are associated with the development of ischemia-reperfusion injury in the liver. Polymorphonuclear neutrophil (PMN) apoptosis is essential to maintain homeostasis and plays a major role in limiting the reperfusion-related systemic effects. This study investigates the effects of a prostacyclin analogue (OP-2507) on hepatic ischemia-reperfusion injury. Adult, male Sprague-Dawley rats were used. Five groups were evaluated: (1) sham-operated control, n = 8; (2) ischemia control (1-h ischemia, 5-h reperfusion), n = 8; (3) intravenous infusion with OP-2507 ([15 cis-14-propylcyclohexyl]-16,17,18,19,20-pentanor-9-deoxy-9alpha,6-ni-trilo-PGF, methyl eater) at a dose of 1 microg/kg/min plus ischemia, n = 8; (4) intravenous infusion with OP-2507 at a dose of 0.1 microg/kg/min plus ischemia, n = 8, and (5) sham-operated control and intravenous infusion with OP-2507 at a dose of 1 microg/kg/min, N =8. Laser-Doppler flowmetry and an in vivo microscopy were used to investigate hepatic microcirculation. PMN apoptosis was quantitated by flow-cytometric labeling of DNA strand breaks. Tissue malondialdehyde and adenosine triphosphate were determined at the end of the experiment. Compared with the ischemia control group, OP-2507 significantly improved harmful insults following ischemia-reperfusion. The changes of mean systemic arterial pressure following ischemia-reperfusion have been significantly attenuated by OP- 2507 at both doses. OP-2507 lessened adherent leukocyte count in the post-sinusoid venules, and improved flow velocity in these areas. OP-2507 at both doses reduced malondialdehyde and increased adenosine triphosphate levels and this effect was dose-related. The activity of delayed ex vivo PMN apoptosis was significantly lower in the ischemia group than that of control and treatment groups. OP-2507 induced the activity of PMN apoptosis and its effect is dose-related, also. The PMN apoptosis activity is strongly correlated with parenchymal damages. This study demonstrates that OP-2507 treatment with ischemia may ameliorate the ischemia-reperfusion injury of the liver in the rat model, and increase spontaneous neutrophil apoptosis ex vivo.

Animals↗

Efficacy and safety of imidapril in patients with essential hypertension: a double-blind comparison with captopril.

In this 12-week, double-blind, parallel-group, comparative trial, 57 adult patients with mild-to-moderate hypertension were randomly allocated to receive imidapril or captopril, initially at a dose of 5 mg once a day and 25 mg twice daily, respectively. After 4 weeks of therapy, the dose of each drug was increased twice if diastolic blood pressure (DBP) remained > or =90 mm Hg. Both treatments effectively lowered DBP in a comparable manner. Mean changes from baseline in DBP at 12 weeks were -9.9 mm Hg for imidapril and -8.8 mm Hg for captopril (p = 0.488). Responder rates in patients receiving active treatment for at least 6 weeks were 53.9% for imidapril and 48% for captopril (p = 0.676). Both treatments were well tolerated. Adverse drug reactions were observed in 20.7% (6/29) of the imidapril group and 46.4% (13/28) of the captopril group (p < 0.05). A cough was the most frequent side effect, reported in 13.8% of the imidapril group and 35.7% of the captopril group. The results indicate that imidapril is as effective as captopril in the treatment of hypertension. Imidapril produces less adverse effects compared with captopril.

Adult↗

Comparison of ischemic patterns in myocardial bridge and syndrome X: evaluation by dobutamine stress echocardiography and stress thallium-201 SPECT.

BACKGROUND AND PURPOSE: Ischemic patterns in patients with syndrome X are thought to differ from those in patients with myocardial bridge, because the mechanisms of coronary flow reduction in these two diseases are different. The aim of this study was to compare the ischemic patterns in patients with syndrome X and those with myocardial bridge through the use of dobutamine stress echocardiography (DSE) and stress thallium-201 single-photon emission computed tomography (SPECT). METHODS: Twenty-six patients with typical angina and stress-induced ST-segment depression were enrolled. All patients underwent coronary angiography, DSE, and stress thallium-201 SPECT within 7 days after enrollment. RESULTS: Of the 26 patients enrolled, 10 had myocardial bridge of the left anterior descending artery and 16 had syndrome X. Among patients with myocardial bridge, myocardial dyssynergy was found by DSE in five patients and reversible or fixed thallium-201 perfusion defects were found in four. Seven patients with myocardial bridge had reverse redistribution patterns on thallium-201 scintigraphy. In the 16 patients with syndrome X, myocardial dyssynergy was found by DSE in only one patient (p = 0.018 vs myocardial bridge group) and reversible or fixed thallium-201 perfusion defects were found in nine (p > 0.05 vs myocardial bridge group). Four patients with syndrome X had reverse redistribution patterns on thallium-201 scintigraphy. The resting left ventricular end-diastolic pressure was higher in patients with myocardial bridge than in those with syndrome X (17 +/- 4 vs 12 +/- 5 mm Hg, p = 0.02). CONCLUSIONS: The most common ischemic patterns in patients with syndrome X were chest pain and stress-induced ST-segment depression, followed by myocardial perfusion defects. Dobutamine-induced dyssynergy was rare. Left ventricular end-diastolic pressure elevation and dobutamine-induced wall motion abnormalities were more common in patients with myocardial bridge than in those with syndrome X.

Adult↗

Laparoscopic cholecystectomy for polypoid lesions of the gallbladder: a clinicopathologic study.

The size and number of gallbladder polyps are used to differentiate between benign and malignant lesions before surgery and to determine whether surgery is necessary for the lesion. Since 1987, laparoscopic cholecystectomy has been widely used as the management method of choice for gallbladder lesions. The results of a clinicopathologic study of polypoid lesions of the gallbladder, based completely on laparoscopically resected gallbladder tissue, have not yet been evaluated fully. Data from 123 patients with polypoid lesions of the gallbladder treated by laparoscopic cholecystectomy were reviewed retrospectively. The gallbladders were classified into four histologic groups. Clinical features, maximal diameter, and the number of lesions were compared among the groups. The mean age of patients with adenoma and cancer was significantly greater than that of patients with cholesterol polyps and other lesions. More women than men had a neoplasm (adenoma and cancer). Patients in the neoplasm group tended to have a single lesion. The mean maximal diameter of neoplasms was significantly larger than that of lesions in the nonneoplasm group. All seven malignant lesions that were detected measured at least 1.5 cm. Univariate analysis showed that polypoid lesions of the gallbladder with neoplastic lesions correlated significantly with age, sex, size, and number of the lesions. Univariate analysis also showed that malignancy in polypoid lesions of the gallbladder correlated significantly with age, size, and number of the lesions. Multivariate logistic regression analysis showed that the age of the patient and the size of the lesion (> or = 1.0 cm) are two independent factors in predicting neoplastic lesions in polypoid lesions of the gallbladder. The size of the lesion (> or = 1.5 cm) is the only independent factor in predicting malignancy in the polypoid lesions of the gallbladder as shown by multivariate logistic regression analysis. Laparoscopic cholecystectomy is a safe and feasible method for gallbladder polypoid lesions. Neoplastic change in polypoid lesions of the gallbladder should be considered when a patient older than 50 years of age has a polypoid lesion larger than 1.0 cm. Cancer should be suspected when a polypoid lesion of the gallbladder is larger than 1.5 cm, and an aggressive surgical approach is warranted so that early gallbladder cancer can be detected and patients can have an increased chance of cure.

Adenocarcinoma↗

Groove pancreatitis: case report and literature review.

Groove pancreatitis is a form of chronic pancreatitis affecting the groove between the head of the pancreas, the duodenum and the common bile duct. It was first described by Becker in 1973. Differentiation between groove pancreatitis and pancreatic head carcinoma is often difficult. Herein, we report a 24-year-old man with groove pancreatitis presenting with epigastralgia, jaundice, fever and vomiting. The diagnosis was confirmed by computed tomography of the abdomen, endoscopic retrograde cholangiopancreatography and surgical exploration. The operative procedures involved were pancreatic biopsy and choledochotomy with T-tube drainage. The patient had an uneventful postoperative course.

Adult↗

A Piscirickettsia salmonis-like bacterium associated with mortality of white seabass Atractoscion nobilis.

Mortality among hatchery-reared juvenile white seabass Atractoscion nobilis in southern California, USA, was associated with infections by a Piscirickettsia salmonis-like organism (WSPSLO). Infected fish had no consistent external signs other than pale gills, lethargy and impaired swimming behavior. Internally, the kidney and spleen were enlarged, and some fish had livers with multiple pale foci. Smears from infected kidney, liver, and spleen stained with Wright-Giemsa had intracytoplasmic coccoid organisms, often in pairs, that ranged in size from 0.5 to 1.0 microm. Microscopic lesions included multifocal hepatic, renal, and splenic necrosis, and intralesional macrophages often contained the WSPSLO. The bacterium was isolated from infected fish on cell lines of salmonid (CHSE-214) and white seabass (WSBK) origin. The WSPSLO induced plaque formation and destroyed the cell monolayers within 10 to 14 d incubation at temperatures of 15 and 20 degrees C. The bacterium retained infectivity for cell lines up to 14 d at 4 and 13 degrees C, up to 7 d at 20 degrees C, but it was inactivated at 37 and 56 degrees C within 24 and 1 h, respectively. Freezing at -20 degrees C reduced infectivity by 100-fold. Dehydration and resuspension in distilled water completely inactivated the bacterium. In contrast, the WSPSLO retained nearly all of its infectivity for CHSE-214 cells following a 72 h period in seawater at 20 degrees C. Polyclonal rabbit antibodies made to the WSPSLO reacted specifically in indirect fluorescent antibody tests (IFAT) with the bacterium in cell cultures and smears from infected fish tissues. Tissue smears from infected salmon or CHSE-214 cells with P. salmonis reacted weakly with the anti-WSPSLO serum. Conversely, polyclonal anti-P. salmonis serum produced a weakly positive reaction with the WSPSLO from infected CHSE-214 cells. The WSPSLO as propagated in CHSE-214 cells was highly virulent for juvenile coho salmon Oncorhynchus kisutch, inducing 80% mortality within 10 d of intraperitoneal injection of 10(2.5)-50% tissue culture infectious doses per fish. We conclude that the bacterium from white seabass possesses antigenic differences from P. salmonis yet possesses virulence for salmon equal to known strains of P. salmonis.

Animals↗

Comparison of simultaneous dobutamine echocardiography and thallium-201 stress-reinjection single-photon emission computed tomography in predicting improvement of chronic myocardial dysfunction after revascularization.

Previous studies have shown that ultrasonic integrated backscatter is valuable in characterizing stunned myocardium. Recent investigations have demonstrated that resting cardiac cycle-dependent variation of integrated backscatter closely paralleled the contractile reserve in patients with chronic left ventricular ischemic dysfunction. The purpose of this study was to validate whether ultrasonic tissue characterization (UTC) compared with dobutamine stress echocardiography (DSE) and thallium-201 stress-reinjection single-photon emission computed tomography (Tl-SPECT) could predict reversible myocardial dyssynergy in patients with chronic coronary artery disease. Forty-eight patients with stable coronary artery disease underwent UTC, DSE, and Tl-SPECT simultaneously before successful coronary revascularization and were followed up with echocardiograms at rest >3 months later. Among the 58 investigated segments, the weighted amplitude, a composite parameter derived from the integrated backscatter power curve, was larger for those groups with greater functional recovery (p <0.001). For the persistent akinetic segments, the weighted amplitudes were small with large deviations of the nadir ratios that represented the asynchrony between the intramural contractile events and the global systole. Using the cut-off value 2.0 of the weighted amplitude, the sensitivity and specificity for predicting functional improvement after revascularization were both 82.8% (kappa = 0.66) and comparable to the sensitivity and specificity of DSE and Tl-SPECT. UTC, delineating the myocardial physical state and intramural contraction, can be a novel approach in predicting functional improvement of chronic dyssynergy after revascularization.

Adult↗

Mutational analysis of the p27(kip1) gene in hepatocellular carcinoma.

p27(Kip1) is an inhibitor of cyclin-dependent kinase. It has been reported that reduced p27(Kip1) expression is present in human hepatocellular carcinoma. To determine the role of p27(Kip1) in hepatocarcinogenesis, 46 cases with hepatocellular carcinomas were studied. p27(Kip1) mutation was first screened by single strand conformation polymorphism, and direct DNA sequencing was then performed on those cases with mobility shifts. Two polymorphism sites were found. One is a previously described polymorphism at codon 109 (GTC-->GGC) which was found in two cases. The second polymorphism was identified at codon 55 (GCG-->GCA) in six of the 46 cases. However, the polymorphism at codon 55 was also present in seven of 93 healthy controls (7.5%), indicating that it is not associated with a predisposition for development of hepatocellular carcinoma (Fisher's exact test, 0.05). These results show that p27(Kip1) mutation is not a frequent event in human hepatocellular carcinoma, and suggest that it may be inactivated predominantly by transcriptional and/or posttranscriptional regulation rather than genomic aberrations.

Adult↗

Dedifferentiation of human hepatocellular carcinoma up-regulates telomerase and Ki-67 expression.

HYPOTHESIS: Dedifferentiation of human hepatocellular carcinoma (HCC) may influence telomerase activation and Ki-67 expression. DESIGN: Laboratory study using human HCC specimens. SETTING: University hospital. PATIENTS: Twelve patients with HCC with specific morphologic patterns (nodule-in-nodule [n = 4] or confluent multinodular [n = 8] type) and histological heterogeneity and who had undergone curative hepatectomy were studied. Of these, 8 patients had 2 different histological grades of HCC cells distributed at various nodules but within the same tumor; 3 patients, 3 different histological grades; and 1 patient, all 4 different histological grades. INTERVENTION: Tissue samples were retrieved from each nodule of the tumor and not mixed with one another. A total of 42 cancerous tissues from different distinctive nodules of the 12 patients were taken for telomerase and Ki-67 study, and corresponding noncancerous counterparts (n = 12) served as healthy control samples. Telomerase activity was assayed by the telomerase repeat amplification protocol. Expression of messenger RNA (mRNA) by the human telomerase catalytic subunit human telomerase reverse transcriptase (hTERT) was determined using reverse transcription polymerase chain reaction. The relative telomerase activity and hTERT mRNA in each tissue sample was quantified using densitometry and expressed as a percentage of the standardized HeLa cell line. Immunostaining with anti-Ki-67 antibody was used to detect Ki-67 and was expressed as Ki-67 labeling index. MAIN OUTCOME MEASURES: Telomerase activity, hTERT mRNA, and Ki-67 labeling index stratified by different histological gradings in each patient was analyzed. The correlations between telomerase activity and hTERT mRNA and between telomerase activity and expression of Ki-67 were plotted. RESULTS: Telomerase activity increased from more to less differentiated foci of HCC cells in each case (generalized linear model, P<.001). Mean +/- SD expression of hTERT mRNA in 43 cancerous tissue samples, even those 4 with negative telomerase activity, was distinguishable from that of the noncancerous controls (0.84 + 0.23 vs 0.41 + 0.11; t test, P =.008). Telomerase activity was correlated to hTERT mRNA expression (Pearson correlation, r(2) = 0.56; P<.001). The Ki-67 labeling index increased from more to less differentiated foci of HCC in each case (generalized linear model, P<.001). Expression of Ki-67 correlated with telomerase activity within differently graded areas within individual tumors (Pearson correlation, r(2) = 0.38; P<. 001). CONCLUSION: Using the model of human HCC with histological heterogeneity, we determined that dedifferentiation of human HCC induces telomerase activation and Ki-67 expression.

Carcinoma, Hepatocellular↗

Hepatectomy for hepatitis B-, hepatitis C-, and dual hepatitis B- and C-related hepatocellular carcinoma in Taiwan.

To evaluate the surgical results of patients with hepatitis B-, hepatitis C- and dual hepatitis B- and C-related hepatocellular carcinoma (HCC), we reviewed the clinical records 252 patients (196 men and 56 women) with complete profiles of hepatitis B and hepatitis C infection who had hepatectomies to treat HCC from March, 1992, to August, 1998. The patients were divided into four groups, 30 patients (11.9%) without either hepatitis B surface antigen or anti-hepatitis C antibody (N-HCC group), 133 patients (52.8%) with hepatitis B infection only (B-HCC group), 66 patients (26.2%) with hepatitis C infection only (C-HCC group), and 23 patients (9.1%) with dual hepatitis B and C infection (BC-HCC group). Compared with the patients in the other groups, the patients in the C-HCC group were older and had more severe cirrhotic change of the liver. The surgical complication rates and hospital mortalities in the C-HCC and BC-HCC groups were 30.3% and 12.1% and 30.4% and 17.4%, respectively, which were higher than those in the N-HCC (13.3%, 3.3%) and B-HCC (15.8%, 3.8%) groups. The mean disease-free survivals for the N-HCC, B-HCC, C-HCC, and BC-HCC groups were 31.4, 25.4, 38.9 and 13.8 months, respectively, with the difference between the four groups being significant (P < 0.05). However, the mean overall survival times, 38.3 months for the N-HCC group, 37.2 months for the B-HCC group, 52.1 months for the C-HCC group, and 32.7 months for the BC-HCC group, were not significantly different (P = 0.146). In conclusion, surgical treatments for HCC related to hepatitis C or dual hepatitis B and C infection were associated with a higher surgical complication rate and hospital mortality. Hepatocellular carcinoma related to dual hepatitis B and C infection recurred earlier after hepatectomy, but the overall survival of the four groups was not significantly different.

Adult↗