Relationship between multiple water swallows and gastroesophageal reflux in patients with normal esophageal motility.

Multiple water swallows (MWS) stimulates neural inhibition, resulting in abolition of contractions in the esophageal body and complete lower esophageal sphincter relaxation, which is followed by peristalsis and the lower esophageal sphincter contraction. We assessed the relationship between MWS and gastroesophageal reflux in patients with esophageal symptoms and with normal findings by high-resolution manometry (HRM). We retrospectively reviewed the clinical records of patients who underwent HRM and a 24-hour ambulatory impedance-pH study. Correlation between the findings of the impedance-pH study and abnormal MWS responses without motility disorders was evaluated. Independent t-tests were used for statistical analysis. Of 28 patients, 20 (71%) had abnormal MWS responses: four (20%) had abnormal responses during MWS, six (30%) had abnormal responses after MWS, and 10 (50%) had abnormal responses both during and after MWS. Total acid exposure times were significantly longer in patients with abnormal MWS responses than in patients with normal MWS responses. In particular, upright acid exposure time and all reflux percent times were significantly longer in patients with abnormal MWS responses. However, bolus clearance time and longest reflux episode were not different between the two groups. Abnormal MWS responses predicted increased acid exposure times in patients with normal findings of HRM by the Chicago classification.

Orientational relationships and atomic arrangements of GaN nanorods grown on Al2O3 (0001) substrates by using hydride vapor phase epitaxy.

Scanning electron microscopy (SEM) images and transmission electron microscopy (TEM) images showed that the one-dimensional GaN nanorods were formed on Al2O3 (0001) substrates by using hydride vapor phase epitaxy without a catalyst. Selected area electron diffraction (SAED) pattern and high-resolution TEM (HRTEM) results showed that GaN nanorods grown on Al2O3 (0001) substrates had crystalline wurzite structures and (0001) preferential orientation. The morphologies of GaN nanorods were affected by the flow rates of the source materials. The orientational relationships between the GaN nanorods and the Al2O3 substrates were (0001)GaN perpendicular (0001) Al2O3 and [0110]GaN perpendicular [1120] Al2O3. Cross-sectional and plan-view atomic arrangements of the fully relaxed interfacial region are described on the basis of the TEM, the SAED pattern, and the HRTEM results.

Cell cycle and immune-related processes are significantly altered in chronic GVHD.

Currently, the pathogenesis of chronic GVHD is unclear. To elucidate the molecular characteristics underlying chronic GVHD, we analyzed the gene expression profiles of 21 mononuclear cell samples from allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Self organizing map (SOM) clustering showed that the entire expression profiles of chronic GVHD samples were clearly different from those of the non-GVHD samples, and significance analysis of microarray (SAM) demonstrated that 120 genes, including PTDSS1, VAV1 and CD3D, were up-regulated, and 5 genes, including calnexin, were down-regulated in GVHD patients. Gene ontology annotation revealed that these genes are related to the phosphorous metabolism and lipid biosynthesis. Quantitative real time polymerase chain reaction (qRT-PCR) experiments validated the up-regulation of PTDSS1, VAV1 and CD3D in separate samples. Pathway-wise global test revealed that differential gene expression in cell cycle and T cell immune-associated pathways were significant between GVHD patients and non-GVHD patients. Seventeen classifier genes selected using a PAM (prediction analysis of microarray) algorithm showed favorable performance (prediction accuracy=0.85) for identifying patients with chronic GVHD. In conclusion, we identified differentially expressed genes and pathways in chronic GVHD patients using microarray analysis, and we also selected diagnostic genes predicting chronic GVHD status.

Sequential isologous organ transplantation in inbred rats: pancreaticoduodenal transplants.

A total of 847 inbred Lewis rats of mixed sex were used in this pancreaticoduodenal (Pd) donor aging study. Pd grafts were taken from 9- to 12-month-old donors and transplanted into 3-month-old recipients (thus, the first generation Pd graft, or 1 Pd). After 9 to 12 months, the same Pd grafts were again harvested and transplanted into 3-month-old rats (thus the 2 Pd generation). This cycle was repeated to obtain the 3, 4, and 5 Pd series. Sequential transplantation was able to extend the Pd grafts' mean survival time to 32 months for fourteen 4 Pd grafts, and to 39.2 months for four 5 Pd grafts (the longest lived graft survived for 42 months). The pancreas and duodenal sections of the grafts remained normal throughout the entire study. However, the aortic sections of the grafts (which were harvested to include the superior mesenteric and celiac arteries) all exhibited moderate to massive atherosclerotic changes by the 5 Pd mean survival age of 39.2 months. Such histological changes commenced even before 21 months of Pd graft age in some animals, gradually progressing to dilation of the aorta (and subsequent narrowing of aortic tributaries), as well as formation of an eggshell-like inner membrane shielding the aortic intima, by 42 months. Such atherosclerotic changes precluded transplantations beyond the 5 Pd series.

Clinicopathologic characteristics of mucinous gastric adenocarcinoma.

There has been considerable controversy over the prognosis of mucinous gastric adenocarcinoma (MGC). In this study we analyzed the clinicopathologic differences between MGC and non-mucinous gastric carcinoma (NMGC). In addition, the relationship between mucin content and other clinicopathologic variables, including prognosis in MGC, was also investigated. We reviewed 2118 patients with pathologically-confirmed gastric cancer who underwent gastrectomy at the Department of Surgery, Yonsei University College of Medicine, during the period between Jan. 1987 and Dec. 1993. Among them, 130 patients had gastric carcinoma with extracellular mucin (MGC) and 1988 patients had gastric carcinoma without extracellular mucin (NMGC). We placed the MGC patients into two groups according to mucin content: mucin content involving over 50% of the tumor (dominant type, n = 94) and mucin content involving less than 50% of the tumor area (partial type, n = 36). The results were as follows: MGC was more common in males than NMGC. The size of the tumor in MGC (mean 5.3 cm) was larger than that of NMGC (mean 4.4 cm). The patients with MGC had a higher incidence of Borrmann type IV (MGC: 16.1%, NMGC: 9.9%), more frequent serosal invasion (MGC: 75.4%, NMGC: 48.6%), lymph-node metastasis (MGC: 75.4%, NMGC: 50.7%), and peritoneal metastasis (MGC: 10.0%, NMGC: 3.5%) than patients with NMGC. The patients with MGC were more advanced in stage at the time of diagnosis and had a worse overall 10-year survival rate (44.9%) than patients with NMGC (54.7%). However, the 10-year survival rate according to the stage of MGC was similar to that of NMGC. There were no significant differences between the mucin content and other pathologic variables, including prognosis, i.e. similar biologic behavior between dominant type MGC and partial type MGC. In conclusion, we suggest that MGC was more frequently diagnosed in advanced stage than NMGC with a poorer prognosis and that it is reasonable to consider the carcinoma with mucin content involving more than 30% of the tumor area as MGC.

Comparison of prognostic significance of nodal staging between old (4th edition) and new (5th edition) UICC TNM classification for gastric carcinoma. International Union Against Cancer.

The description of nodal staging for gastric cancer was changed in the new fifth edition of the International Union Against Cancer (UICC) TNM classification from the anatomic sites of metastatic lymph nodes to the number of metastatic lymph nodes, as pN1 is metastasis in 1 to 6 lymph nodes, pN2 is in 7 to 15 lymph nodes, and pN3 is in 16 or more lymph nodes. The purpose of this study was to investigate the prognostic significance of the new staging system based on the number of metastatic lymph nodes compared to the old staging system by anatomic site. From 1987 to 1994 a total of 2108 patients who underwent potentially curative resections with D2 or D3 lymph node dissection and with 15 or more lymph nodes retrieved were studied retrospectively. Lymph node metastases were found in 1018 patients (48.3%). A mean of 37.9 lymph nodes were retrieved per patient, and a mean of 7.2 lymph nodes were invaded by tumor cells. We found that the new nodal staging based on the number of metastatic lymph nodes closely correlated with the depth of cancer invasion and with the old nodal staging based on the anatomic site of the metastatic nodes, with statistical significance. The 5-year survival rates after gastrectomy decreased significantly by increasing the extent of the pN classification in both nodal staging methods. In a subgroup analysis of survivals between the old and new nodal staging, the new classification showed more homogeneous survival at the same stage than the old one. With a multivariate analysis of prognostic factors, including the old and new nodal staging, the depth of invasion and the new nodal stage were the most significant prognostic factors, followed by the old nodal stage. Our data suggested that the new nodal staging based on the number of metastatic lymph nodes is not only a reliable and objective method for nodal classification, but it is also a significant prognostic determinant for gastric cancer that can be used in practice.

Prognostic significance of CD44 and nm23 expression in patients with stage II and stage IIIA gastric carcinoma.

BACKGROUND AND OBJECTIVES: Predicting the prognosis in gastric carcinoma patients with intermediate stages is difficult. We investigated the prognostic impacts of CD44 and nm23 expression in a homogeneous group of patients with stage II and IIIA gastric carcinoma who had undergone curative resections. METHODS: A total of 261 paraffin-embedded gastric carcinomas were stained with the monoclonal antibodies CD44 and nm23 using the labeled streptovidin biotin method. RESULTS: The expression of CD44 and nm23 was detected, respectively, in 31.0% (81/261) and 70.1% (183/261) of all tumors. There was no correlation between CD44 expression and clinicopathological variables. However, nm23 was more frequently expressed in older patients with differentiated adenocarcinoma. A significant difference in 5-year survival rates was found between patients with CD44-positive (43.2%) and CD44-negative tumors (63.4%), (P = 0.0018). However, there was no significant difference in 5-year survival rates between patients with nm23-positive (54.7%) and nm23-negative tumors (62.7%) (P = 0.2734). CONCLUSIONS: CD44 expression was a significant adverse prognostic factor in gastric carcinoma and may be a predictor of metastatic potential of the primary tumor. By contrast, immunohistochemical detection of nm23 expression was not a predictor of outcome of patients with gastric carcinoma.

Recurrence following curative resection for gastric carcinoma.

BACKGROUND: The diagnosis and treatment of recurrent gastric cancer remains difficult. The aim of this study was to determine the risk factors for recurrence of gastric cancer and the prognosis for these patients. METHODS: Of 2328 patients who underwent curative resection for gastric cancer from 1987 to 1995, 508 whose recurrence was confirmed by clinical examination or reoperation were studied retrospectively. The risk factors that determined the recurrence patterns and timing were investigated by univariate and multivariate analysis. RESULTS: The mean time to recurrence was 21.8 months and peritoneal recurrence was the most frequent (45.9 per cent). Logistic regression analysis showed that serosal invasion and lymph node metastasis were risk factors for all recurrence patterns and early recurrence (at 24 months or less). In addition, independent risk factors involved in each recurrence pattern included younger age, infiltrative or diffuse type, undifferentiated tumour and total gastrectomy for peritoneal recurrence; older age and larger tumour size for disseminated, haematogenous recurrence; and older age, larger tumour size, infiltrative or diffuse type, proximally located tumour and subtotal gastrectomy for locoregional recurrence. Other risk factors for early recurrence were infiltrative or diffuse type and total gastrectomy. Reoperation for cure was possible in only 19 patients and the mean survival time after conservative treatment or palliative operation was less than 12 months. CONCLUSION: The risk factors for each recurrence pattern and timing of gastric cancer can be predicted by the clinicopathological features of the primary tumour. Since the results of treatment remain dismal, studies of perioperative adjuvant therapy in an attempt to reduce recurrence are warranted.

Early postoperative intraperitoneal chemotherapy with mitomycin C, 5-fluorouracil and cisplatin for advanced gastric cancer.

OBJECTIVE: The long-term survival of patients who undergo surgery for stage IV gastric cancer is poor, due to metastatic spread of the tumor. Intraperitoneal chemotherapy (IPT) as a possible treatment for peritoneal dissemination has been investigated in a number of different tumors. The aim of this study was to investigate the toxicity and impact of early postoperative IPT on the survival of patients with advanced gastric cancer. METHODS: Between 1993 and 1997, a total of 91 patients with stage IV gastric cancer who underwent potentially curative or palliative resection received intraperitoneal mitomycin C before closure of the abdominal wound. 5-Fluorouracil and cisplatin were administered intraperitoneally on postoperative days 1-4, and this was repeated at 4-week intervals. RESULTS: All patients received a median of 3 IPT perfusions. There were 24 (26.4%) postoperative complications and 1 (1.1%) mortality. The most frequent hematologic toxicity (grade 3-4) was leukopenia. The major nonhematologic toxicities (grade 3-4) were emesis and nephrotoxicity. After a median follow-up period of 26 months, 14 patients remain alive without evidence of recurrence, whereas 75 patients died due to recurrence or progression of disease. The median survival period for all 91 patients was 15.4 months. When survival according to the residual tumor was analyzed, median survival was 36.0 months in the R0 (curative resection) group, 20.6 months in the R1 group (margins of resected specimens showing microscopic residual tumor or diameter of each residual tumor less than 3 mm) and 9.0 months in the R2 group (macroscopic residual tumor larger than 3 mm) (p < 0.001). CONCLUSIONS: IPT was found to be safe, and it appears to improve the prognosis in patients with minimal residual tumors. However, complete cytoreductive surgery is mandatory for achieving the beneficial effect of IPT.

An active noise control algorithm for controlling multiple sinusoids.

The filtered-x LMS algorithm and its modified versions have been successfully applied in suppressing acoustic noise such as single and multiple tones and broadband random noise. This paper presents an adaptive algorithm based on the filtered-x LMS algorithm which may be applied in attenuating tonal acoustic noise. In the proposed method, the weights of the adaptive filter and estimation of the phase shift due to the acoustic path from a loudspeaker to a microphone are computed simultaneously for optimal control. The algorithm possesses advantages over other filtered-x LMS approaches in three aspects: (1) each frequency component is processed separately using an adaptive filter with two coefficients, (2) the convergence parameter for each sinusoid can be selected independently, and (3) the computational load can be reduced by eliminating the convolution process required to obtain the filtered reference signal. Simulation results for a single-input/single-output (SISO) environment demonstrate that the proposed method is robust to the changes of the acoustic path between the actuator and the microphone and outperforms the filtered-x LMS algorithm in simplicity and convergence speed.

Proximal gastrectomy and jejunal pouch interposition: radiographic evaluation of postoperative findings.

BACKGROUND: We assessed the postoperative findings of proximal gastrectomy and jejunal pouch interposition with contrast radiography. METHODS: Eleven patients with proximal gastrectomy and jejunal pouch interposition for proximal gastric carcinoma underwent contrast radiography. We evaluated the radiographic findings of the remnant stomach and interposed jejunal pouch. RESULTS: The interposed jejunal pouch showed good expansion, and the motility of the remnant gastric antrum was normal in all patients. One patient had significant lumenal narrowing of the esophageal pouch anastomotic site. Leak at the anastomotic site was not found. Reflux into the esophagus from the pouch was observed in two patients. Gastric emptying time was considerably delayed in two patients. CONCLUSION: Follow-up upper gastrointestinal series of the proximal gastrectomy and jejunal pouch interposition showed different postoperative findings. Awareness of the normal and abnormal findings is essential in the accurate postoperative evaluation of these patients.

Transplantation of reproductive organs.

A historical review of the literature concerning replantation and transplantation of reproductive organs has included studies from this laboratory, using rats, over the past 25 years. From the basic observation of ischemic and traumatic injury due to the transplantation, syngeneic testicle transplants, resulting in a partner's impregnation and histological restoration of the testicles, led to human testicular transplantation. As to the ovarian transplants, granulosa-theca cell tumors may transform into malignancies if followed for a prolonged period as intrasplenic ovaries, and high doses (15 to 20 mg/kg b.w.) of azathioprine can produce such malignant tumors in a shorter period. By caval-portal shunt, ovarian hormones enter directly into the portal blood stream and no typical granulosa-theca cell tumors were produced, owing to the fact that the liver cannot degrade all the hormones secreted by both ovaries. While en-bloc vagino-utero-ovarian transplantation in the rat is possible, no impregnation has been yet achieved. Finally, it is hypothesized that those who have acquired microsurgical techniques and have a full understanding of the anatomy of the reproductive system will not only be able to perform replantation of the penis, but also will be capable of allogeneic transplantation of genital organs, whether ethically approved or not, and sooner than one may think. In such cases a penile part may be obtained at a sex-change surgery or from a cadaveric donor, similar to other vital organ transplantation practices.

Consecutive en-bloc liver (30%)-pancreas-duodenum-spleen-stomach transplant in Lewis rats.

It is well-known that 30% of the remaining liver mass, following partial hepatectomy, regenerates to full original mass within 2 weeks in rats. In order to carry the transplanted rat liver to repeated transplantation, a technique of combining 30% of the liver with the pancreaticoduodenum and spleen transplantation is performed in this consecutive organ transplantation study. Our laboratory observed several 37-month-old transplanted rats by carrying through 2-3 generations, and histological disclosure were made. Because the partial liver transplants did not regenerate after the transplantation with other splanchnic organs, this technique is not so difficult though subsequent surgical maneuvers are needed and the liver histology proved entirely normal in every aspect when followed beyond the rat's life span of 24 months.

Needles to promote ventricular blood into the ischemic myocardium applied in a rat heart transplant model: an acute observation [corrected].

Two needles were designed in order to revascularize an ischemic myocardium in the event of left coronary artery occlusion. This study was conducted by performing the Lee modified Fox-Montorsi heart-lung transplant on 25 San Diego Microsurgical Institute-bred Sprague Dawley rats that were subjected to left coronary artery ligation in each case. Of these 25 rats, a straight-porous (SP) needling procedure was applied to 9 heterotopically transplanted rat hearts, and a distinct horseshoe (HS)-shaped needle application was performed on the remaining 16 heterotopically transplanted rat hearts. This report represents an acute study on the efficiency of these two needles to transmit oxygen-rich blood from the left ventricle into the ischemic myocardium. Doppler readings for male vs. female transplants showed that the control peak (PK) and mean (MN) kHz values are on the average of 0.20 kHz higher in males than in females. However, control heart rate values in both sexes are approximately equal. Ligation of the left coronary artery caused a dramatic decrease of PK and MN kHz values in both sexes, while heart rate showed no significant decrease from the original control values in response to ischemia. Application of the SP needle showed only a slight return of PK and MN values in both sexes, but heart rate values increased to levels higher than the original control values. The HS needling procedure was able to recover approximately 80% of the control PK and MN kHz values in both sexes. Thus, these data indicate that the HS needle can successfully transmit left ventricular blood into the myocardium.

Observations of rat ovarian-splenic consecutive transplants.

We examined the results after implantation of ovarian follicles by various modes in a total of 82 cases. One or five ovarian follicles were implanted into spleens in castrated female rats. In 20 cases among these, each five follicles were implanted into native and transplanted spleens after spleen transplantation (double implantation of the ovary). Through consecutive spleen transplantation, we observed the results beyond the rat's life span for a limited period. In many cases, we found a more aggressive form of malignant tumor, i.e., dysgerminoma. We present the results and discuss the modes of implantations and possible pathogenetic mechanisms of tumor formation.

Structure-activity relationship study of asiatic acid derivatives against beta amyloid (A beta)-induced neurotoxicity.

8 Semi-synthetic derivatives of asiatic acid were prepared and their protective effect against A beta-induced neurotoxicity was evaluated. Among them, asiatic acid (2), and 4, 16 showed 97, 92 and 87% of protective effect, respectively.