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Biomedical subjects

P W Lin

Publications and source records attributed to P W Lin.

At least 37 records · Page 2Linked to original sources

Analysis of K-ras gene mutations in periampullary cancers, gallbladder cancers and cholangiocarcinomas from paraffin-embedded tissue sections.

Point mutations of the K-ras gene were analyzed in 25 periampullary cancers (21 ampulla vater cancers, two common bile duct cancers and two duodenal cancers), two gallbladder cancers and six cholangiocarcinomas. DNA extracted from the paraffin-embedded tissues was amplified with the polymerase chain reaction and subsequently analyzed by direct cycle sequencing at codons 12, 13 and 18 of the K-ras gene. Codon 61 was first screened with single strand conformation polymorphism and then sequenced by direct cycle sequencing. No point mutation was found in any of the 25 periampullary cancers or the two gallbladder cancers. These results are similar to previous reports. Mutation of the K-ras gene seems not to play an important role in tumorigenesis of periampullary cancer. In two of six (33%) cholangiocarcinoma patients, point mutations were found. Both mutations were transitions, GGT to GAT at codon 12. The incidence of mutation was greater than that in Thailand (about 8%) but less than that in Japan (about 60%). Mutation of the K-ras gene may play varied roles in the tumorigenesis of cholangiocarcinoma, depending on geographic area.

Adult↗

Portal hemodynamics and humoral factors involved in a portal hypertensive rabbit model.

Hemodynamic changes and certain humoral factors possibly responsible for splanchnic hyperemia in portal hypertensive rabbits created by partial portal vein ligation were studied. Portal pressure was significantly elevated after portal vein ligation and reached a climax on the second day. Then, it decreased but still remained at a plateau in a portal hypertensive state in the following days. Portal blood flow, measured with an electromagnetic flowmeter, had no significant change immediately after portal vein ligation and on post ligation day-1, but it increased significantly from the second day. Portal venous resistance rose significantly from the basal state immediately after portal vein ligation, then, it decreased from the second day, but still remained at a high resistance level as compared with the normal (p < 0.05). The levels of prostaglandin E2 and prostacyclin in the portal vein increased immediately after portal vein ligation but decreased on the second day. However, prostacyclin rose again on the fifth day. It is apparent from this study that once portal pressure or portal resistance increases, there is a surge of prostaglandin E2 and prostacyclin in the portal blood. Due to the vasodilation effect of prostacyclin, prostaglandin E2 and other possible vasodilators, portosystemic shunts are gradually produced, and splanchnic hyperemia develops in the portal hypertension. The initial mechanism of portal hypertension in this model was due mainly to an increase in resistance. At a later stage, increased splanchnic blood flow combined with increased resistance played an important role in the maintenance of portal hypertension.

Animals↗

Influence of paraesophageal venous collaterals on efficacy of endoscopic sclerotherapy for esophageal varices.

To determine the diagnostic accuracy of computer tomography in the detection of venous collaterals surrounding the esophagus in patients with portal hypertension, preoperative computer tomography interpretations of these veins in 15 patients who were candidates for the Sugiura procedure for treatment of esophageal varices were correlated with those of the intraoperative assessment. Laparotomy revealed severe paraesophageal varices in five patients; four of them were found to have paraesophageal varices in computer tomography films. The sensitivity and specificity of computer tomography in diagnosing severe paraesophageal varices were 80% and 100%, respectively. A second assessment was performed in 59 additional patients with esophageal variceal hemorrhage to investigate the influence of paraesophageal varices on the efficacy of endoscopic sclerotherapy in the treatment of varices. The patients were divided into two groups: Group A included 17 patients with and group B 42 patients without paraesophageal varices on presclerotherapy computer tomography. All patients underwent elective sclerotherapy after being deemed hemodynamically stable. Patients in group A required more treatment sessions, more sclerosant and longer periods to obliterate varices completely than did group B patients. Eight patients in group A and six in group B (57% vs. 16%, p < 0.05) had variceal recurrence after obliteration during mean follow-ups of 20.8 and 19.9 mo, respectively. The mean time elapsed before variceal reappearance was shorter for group A than for group B (4.1 +/- 3.3 vs. 11.8 +/- 2.7 mo, p < 0.05). Among patients who developed new varices, five patients in group A and one in group B experienced repeat bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)

Collateral Circulation↗

Measurement of organ volume by single photon emission computed tomography.

The aim of this study was to develop a new algorithm for volume determination by single photon emission computed tomography (SPECT). Different algorithms were evaluated through phantom studies. The results show that the algorithm combining moment-preserving bilevel thresholding and best-fit Laplacian second derivative edge detection can provide the most accurate measurement of volume. Besides, this method can be utilized in different SPECT systems with no need for further phantom studies. In patient studies, the results of liver volume calculation have indicated that this is a useful technique in clinical medicine.

Algorithms↗

Effect of octreotide on hemodynamics and glucagon levels in portal hypertensive rabbits.

This study was designed to investigate the effect of octreotide (Sandostatin, Sandoz), an analogue of somatostatin, on the hemodynamics and glucagon level in portal hypertension. Sixteen portal hypertensive rabbits produced by partial ligation of the portal vein two weeks earlier received an intravenous infusion of octreotide at a dose of 30 micrograms/h. After infusion of octreotide, a significant reduction in portal venous pressure from 16.2 +/- 3.9 mmHg (mean +/- SD) to 13.3 +/- 4.3 mmHg at 21 minutes and 12.0 +/- 4.5 mmHg 42 minutes was noted. A persistent decrease in portal pressure to 11.0 +/- 4.5 mmHg 21 minutes after stopping infusion of octreotide was also observed. Portal venous blood flow was decreased significantly from 60.9 +/- 13.1 mL/min to 46.9 +/- 15.0 ml/min at 21 minutes and to 45.8 +/- 12.8 ml/min at 42 minutes. A slight elevation of portal blood flow to 49.0 +/- 14.1 ml/min was noted 21 minutes after cessation of octreotide infusion. Portal venous resistance was slightly elevated during infusion of octreotide (before infusion: 2.2 +/- 1.4 dyne.s.cm-5, 21 minutes after infusion: 2.4 +/- 1.4 dyne.s.cm-5 and 42 minutes after infusion: 2.3 +/- 1.3 dyne.s.cm-5), and decreased (1.9 +/- 1.0 dyne.s.cm-5, p < 0.1) with a forward significance after stopping infusion. There were no significant changes in systemic arterial pressure during this experiment. A significant decrease (p < 0.05) in glucagon level from 323 +/- 93 pg/dl to 267 +/- 62 pg/dl at 21 minutes and to 298 +/- 88 pg/dl at 42 minutes in the portal vein was noted during the infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of splenectomy, devascularization and esophageal transection on portal venous pressure and portal perfusion in cirrhotic patients with bleeding esophageal varices.

This investigation sought to determine the effects of splenectomy, devascularization and esophageal transection on portal venous pressure and portal perfusion in cirrhotic patients with a previous history of hemorrhage from esophageal varices. From June 1988 to June 1991, 54 patients with liver cirrhosis underwent this nonshunting procedure for esophageal varices. Of these patients, 24 patients (20 men and four women, 39 to 68 years of age, all in Child's class A) were examined for portal pressure before, during and after the nonshunting operations. Portal venous perfusion was assessed from the venous phase of the superior mesenteric arteriogram preoperatively and one year after surgery in 16 of these 24 patients. There was no significant change (p > 0.05) in cardiac output and systemic blood pressure after the operation. The portal venous pressure before surgery was 28.4 +/- 8.0 mmHg with a range from 18 to 44 mmHg. A statistically significant decrease (p < 0.05) in the portal pressure was observed after ligation of the splenic artery (26.6 +/- 8.9 mmHg), splenectomy (24.8 +/- 8.0 mmHg), and devascularization with transection (23.4 +/- 7.5 mmHg). No correlation between the portal pressure change and splenic weight was noted (p > 0.05). Postoperative portal perfusion remained the same or even improved in 15 of these 16 patients. Only in one patient was the portal perfusion worse after the operation; this patient developed encephalopathy about 18 months later. In conclusion, a significant reduction in portal pressure is noted after nonshunting procedures but a persistent, relatively high portal pressure is maintained. Good postoperative portal perfusion can also be maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effects of splenectomy and splenic artery ligation on the portal pressure in portal hypertensive rats.

Immediate, short-, and long-term effects of splenectomy and splenic artery ligation on the portal pressure were studied in animal models experimentally created by partial portal vein ligation. The portal pressure of these animals would usually elevate immediately after partial ligation of the portal vein from a normal level of 6.0 +/- 0.5 to 14.8 +/- 1.3 mm Hg (P < 0.005), which could be maintained at least for 6 months. The portal pressure measured at 2 weeks, 4 weeks, and 6 months after portal vein ligation was 14.0 +/- 2.7, 15.2 +/- 2.7, and 12.7 +/- 2.0 mm Hg, respectively (P < 0.005, as compared with the normal). When splenectomy was performed on these animals at 2 weeks after partial portal vein ligation, the pressure dropped immediately but only transiently from 14.0 +/- 2.7 to 11.0 +/- 3.0 mm Hg, and bounced back to the presplenectomy level in 20 sec. After an additional 2 weeks, the portal pressure in these splenectomized rats was usually at 15.2 +/- 4.2 mm Hg, which was indistinguishable from that of rats whose portal vein was ligated but the spleen was not removed. Six months after splenectomy, however, the portal hypertensive rats had a portal pressure of 17.1 +/- 6.4 mm Hg, which was significantly higher than that of the controls. Splenic artery ligation, on the other hand, did not result in any immediate decrease in portal pressure (14.0 +/- 2.7 mm Hg vs 14.6 +/- 1.4 mm Hg; P > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pancreas divisum with early pancreatic cancer--presenting as chronic obstructive pancreatitis.

A 61-year-old man experienced four bouts of pancreatitis in 1 year. Detailed history taking and a series of examinations, including sonography, computed tomography scan, and endoscopic retrograde cholangiopancreatography (ERCP), revealed pancreas divisum on the first admission. He was treated conservatively. However, repeated ERCP on the fourth admission, 1 year later, showed a small filling defect in the tail of the pancreatic duct. A distal pancreatectomy was carried out. Pathological studies revealed a small papillary adenocarcinoma (1.5 x 1.0 x 0.5 cm) confined to the pancreatic duct grossly with minimal parenchymal invasion microscopically. He has been free from cancer and pancreatitis for 13 months since the operation.

Adenocarcinoma↗

Effects of splenectomy on portal pressure in short- and long-term portal hypertensive rats.

Different hemodynamic patterns were noted in short- and long-term portal hypertensive rats, induced by partial portal vein ligation (PVL) performed two weeks and six months earlier. In order to investigate the effect of splenectomy on the portal pressure of portal hypertensive rats with different hemodynamics, an operation was performed on these two groups of animals and the portal pressure measured thereafter at different time points. Splenectomy in the short-term group produced an immediate, but transient, drop in portal pressure from 14.1 +/- 2.7 to 11.0 +/- 3.0 mmHg, which bounced back to pre-splenectomy values in 20 seconds. Two weeks later, the portal pressure in these splenectomized rats was 15.2 +/- 4.2 mmHg, which was indistinguishable from that of the pre-splenectomy condition of the short-term group. However, after an additional two weeks, portal pressure in the splenectomized rats rose to 16.4 +/- 2.1 mmHg, which was significantly higher than that of the pre-splenectomy condition of the short-term group. This difference in portal pressure became even more pronounced at six months. Sustained portal hypertension was observed in the long-term group, but the pressure was significantly lower than that in the short-term group. Splenectomy in the long-term group produced neither an immediate drop nor a delayed rebound in portal pressure. We conclude that splenectomies in portal hypertensive rats at different stages of disease produce different effects.

Animals↗

A clinical pregnancy after a simple method of zona cutting, cryopreservation, and zygote intrafallopian transfer.

A 30-year-old nulliparous woman, who was infertile for greater than 3 years, conceived after the procedures of a simple method of zona cutting, cryopreservation, and ZIFT. This case illustrates: (1) acid medium, chymotrypsin, or sucrose are not needed for the procedure of zona cutting; (2) the zygotes resulting from zona cutting survive through freezing and thawing; and (3) oocyte retrieval can be done concomitant with conservative surgery for endometriosis.

Adult↗

Postirradiation angiosarcoma of the terminal ileum.

Sarcomas which develop after radiotherapy mainly involve the soft tissue and the bone. Postirradiation angiosarcomas involving the internal organs are exceedingly rare and so far only three cases have been reported. Here, a case of angiosarcoma of the terminal ileum in a 48-year-old female is reported. The tumor developed 39 months after radiotherapy for recurrent squamous cell carcinoma of the uterine cervix. Angiosarcoma recurred locally and metastasized to the liver eight months after initial resection of the primary lesion of the terminal ileum. The patient died from sepsis 23 days after the resection of the recurrent ileal and metastatic hepatic neoplasms. Hence, any patients complaining of new discomfort that occurs in an irradiated field two years or more after radiotherapy should be promptly searched for the presence of the postirradiation neoplasms.

Female↗

Lead, cadmium, arsenic, and mercury levels in maternal and fetal cord blood.

In this study the levels of lead, arsenic, cadmium and mercury were measured by the method of graphite-furnace atomic absorption spectrophotometry in paired maternal and fetal cord blood (n = 168) collected from three cities in Taiwan, (Kaohsiung, Taipei and Keelung). The mean values of those heavy metals were within normal limits. There was no difference in levels by maternal parity or fetal sex. The mean value for the level of lead in maternal blood was 64.8 micrograms/L, and 40.9 micrograms/L for the umbilical-cord blood; comparing the three locations by ANOVA analysis, there was no difference in maternal or fetal blood levels. Mean maternal As concentrations (6.8 +/- 0.58 micrograms/L) and umbilical cord blood levels (7.9 +/- 0.67 micrograms/L) were within reference levels. The mean Cd concentrations in maternal blood were (1.30 micrograms/L) significantly higher than that of the umbilical-cord blood concentrations (0.78 micrograms/L). The maternal Cd concentrations (1.62 micrograms/L) of Kaohsiung were significantly higher than that (1.24 micrograms/L) of Taipei. The fetal Cd concentrations of Kaohsiung (1.04 micrograms/L) were also significantly higher than those (0.7 micrograms/L, 0.6 micrograms/L) of Taipei and Keelung. The mean umbilical-cord blood Hg concentration (28.8 micrograms/L) was higher than that (19.4 micrograms/L) of maternal blood. The maternal Hg concentrations of Taipei were significantly higher than those of Keelung. The fetal Hg concentrations (28.8 micrograms/L) of Taipei were also marginally higher than that of Keelung and Kaohsiung.

Arsenic↗

Hemodynamic changes after hepatectomy in rats studied with radioactive microspheres.

It has been difficult to measure hepatic arterial blood flow and portal venous flow simultaneously, especially in small animals. Radioactive microspheres were used in this experiment to quantitate splanchnic hemodynamics after hepatectomy in rats. With a reference sample technique, a certain amount of radioactive microspheres was injected into the left ventricle. The reference sample was withdrawn from the femoral artery at a constant rate. The animal was killed with a bolus of saturated KCl. The kidneys and splanchnic organs were removed and weighed. The radioactivity of each organ was determined using a gamma scintillation counter. Organ blood flow was calculated by the following formula: [formula: see text] Immediately after partial hepatectomy, a decreased cardiac index from 32.31 +/- 10.12 to 23.44 +/- 3.21 ml/(min x 100g body weight) (p less than 0.05), decreased hepatic arterial blood flow from 0.40 +/- 0.12 to 0.33 +/- 0.03 ml/(min x g liver) (p less than 0.05), increased portal venous inflow from 0.90 +/- 0.30 to 2.20 +/- 0.26 ml/(min x g liver) (p less than 0.05) and increased total hepatic blood flow from 1.30 +/- 0.39 to 2.53 +/- 0.26 ml/(min x g liver) (p less than 0.005) were observed. With an intrasplenic injection of an additional amount of radioactive microspheres, the ratio of lung/(lung + liver) radioactivities indicated the degree of portal systemic shunt (PSS). Though the portal pressure was elevated after hepatectomy (8.80 +/- 0.7 vs 11.9 +/- 1.7 cm H2O, p greater than 0.05), the extent of PSS was negligible (0.02 +/- 0.01% vs 0.03 +/- 0.01%, p greater than 0.05). The radioactive microspheres with the reference sample technique is a simple, rapid, reliable and reproducible method for investigating the hemodynamic changes following partial hepatectomy.

Animals↗

Prostacyclin mediates splanchnic vascular response to norepinephrine in portal hypertension.

Portal hypertension is characterized by increased splanchnic blood flow. This hyperemia may be related to the documented in vitro impaired sympathetic response in portal hypertension. Because prostacyclin (PGI2) has been shown to be elevated in portal hypertensive rabbits, we studied whether PGI2 could mediate the reduced sympathetic response. We measured the change in the superior mesenteric artery resistance (Rsma) to norepinephrine infusion in chronic portal vein ligated (PHT) and normotensive rabbits, in both portal hypertensives and normals following cyclooxygenase blockade with 8 mg/kg indomethacin, and finally in portal hypertensive, cyclooxygenase-blocked rabbits with a constant IV infusion of PGI2 at 200 or 300 ng/kg/min. Dose-response curves were obtained and statistical comparisons were based on the dose of norepinephrine producing 50% of maximal Rsma response (ED50). Portal hypertensive rabbits had significantly higher ED50 (310 +/- 4.1 mg/kg) than normotensive rabbits (150 +/- 4.1 mg/kg, P less than 0.01). Cyclooxygenase blockade resulted in marked reduction of the ED50 in both groups and ablated the difference between normotensive and PHT rabbits (20 +/- 2.4 and 20 +/- 2.8 mg/kg/min, respectively). Prostacyclin infusion at 200 ng/kg/min increased the ED50 (80 +/- 2.5 mg/kg) and PGI2 infusion at 300 ng/kg/min increased the ED50 further (160 +/- 7.5 mg/kg/min, P less than 0.01 vs cyclooxygenase-blocked only rabbits). These results provide the first in vivo evidence of reduced splanchnic sensitivity to norepinephrine in portal hypertension and demonstrate that PGI2 will cause a dose-related decrease in sympathetic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A method for hepatic arterial perfusion studies in the rat.

The current model for selective hepatic arterial infusion therapy was evaluated for its suitability for short-term pharmacokinetic experiments. This preparation consists of selective cannulation of the common hepatic artery via the gastroduodenal artery of the rat. Radioactive microspheres were injected to determine hepatic or extrahepatic sites of perfusion. Radioactive microsphere determination of hepatic arterial flow and cardiac output were also performed. Our data indicate that at high flow rates (2 ml/min), significant loss of drug would occur due to retrograde flow. Modification of the model to include temporary proximal hepatic artery occlusion ensures hepatic delivery of greater than 95% of drug. Furthermore, temporary hepatic artery occlusion does not alter cardiac output or hepatic arterial blood flow. Selective hepatic arterial infusion in rats with synchronous temporary hepatic artery occlusion is an adequate model for short-term pharmacokinetic studies.

Animals↗

Simple, effective procedure with few complications for esophageal varices.

The surgical morbidity, mortality, and effectiveness of a modified nonshunting operation that includes splenic artery division instead of splenectomy, devascularization, and esophageal transection (SAD group) were evaluated. Eighteen cirrhotic patients with varices who underwent this modified procedure were compared with 54 patients treated with a conventional nonshunting operation (splenectomy group). Results show that immediate effects on portal pressure and preservation of portal perfusion between the two groups were similar. The operative time is shorter (p < 0.05), and the bleeding amount is less (p < 0.005) in the SAD group than in the splenectomy group. No surgical mortality and no major complications were noted in the SAD group. A surgical mortality of 2.3% and 30% was noted for the elective and emergency operations of the splenectomy group, respectively. There was no encephalopathy in the SAD group but one in the splenectomy group. Recurrent bleeding occurred in three patients of the splenectomy group 1 year after surgery but none in the SAD group. These data indicate that this modified procedure is a simple and effective operation with few complications for esophageal varices.

Adult↗