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Results from pelvic exenteration for locally advanced colorectal cancer with lymph node metastases.

PURPOSE: We examined the survival benefit of pelvic exenteration for locally advanced colorectal cancer with lymph node metastases, because this issue remains controversial. METHODS: Medical records of 50 patients who underwent curative pelvic exenteration for colorectal cancer were reviewed retrospectively. Nodal metastases were examined by the clearing method in 29 patients and by the conventional manual method in 21 patients. RESULTS: Invasion to contiguous pelvic organs was present in 40 patients (80 percent) and absent in 10 patients (20 percent). Node metastases were present in 33 patients (66 percent). Operative morbidity and mortality rates were 22 percent (11 patients) and 6 percent (3 patients), respectively. Respective five-year survival rates were 60 and 80 percent in the groups with and without organ invasion (no significant difference). Five-year survival rates in patients with nodal metastases was 54.6 percent but was significantly higher, 82.4 percent, in patients without nodal metastases. Five-year survival in 28 patients with both organ invasion and nodal metastases was 53.6 percent. CONCLUSIONS: Long-term survival was afforded by pelvic exenteration for locally advanced colorectal cancer with nodal metastases.

Colorectal Neoplasms↗

Expression of multidrug resistance-related transporters in human breast carcinoma.

The expression levels of mRNA for multidrug resistance 1 (MDR1) gene, multidrug resistance protein 1 (MRP1), lung resistance-related protein (LRP) and breast cancer resistance protein (BCRP), which confer multidrug resistance in vitro, were examined in 43 untreated breast carcinoma patients, of whom 38 subsequently received doxorubicin-based chemotherapy after surgery, in order to elucidate the roles of these genes in drug resistance in vivo. The mRNA levels were determined using a semi-quantitative reverse-transcription polymerase chain reaction method in breast carcinoma tissues including at least 80% carcinoma cells. The expression level of BCRP gene was low and did not vary markedly in comparison with that of MDR1, MRP1 or LRP gene. The expressions of MDR1 and MRP1 genes were correlated with each other, but the expression of BCRP or LRP gene did not correlate with that of other genes. These four gene expressions were independent of age, TNM categories and the status of progesterone or estrogen receptor. The expression levels of these four genes were not related to the relapse or prognosis of the 38 patients treated with doxorubicin-based chemotherapy. P-glycoprotein (P-gp) / MDR1, MRP1 and LRP may play more important roles than BCRP in chemotherapy of human breast carcinoma.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Expression of glial cell line-derived neurotrophic factor (GDNF) and GDNF family receptor alpha1 in mouse taste bud cells after denervation.

Glial cell line-derived neurotrophic' factor (GDNF) has been isolated as a neurotrophic factor that affects the survival and maintenance of central and peripheral neurons. Using immunocytochemical methods, we examined whether the taste bud cells in mouse circumvallate papillae after transection of the glossopharyngeal nerves expressed GDNF and its receptor, GDNF family receptor alpha1 (GFRalpha1). By 5 and 10 days after denervation, the number of taste buds had decreased markedly; however, the remaining taste bud cells still expressed GDNF and GFRalpha1. By 14 days after denervation, most of the taste buds had disappeared and GDNF- and GFRalpha1-immunoreactive cells were not seen. By 4 weeks after denervation, numerous TrkB-immunoreactive nerve fibers had invaded the papilla and a few taste buds expressing GDNF and GFRalpha1 had regenerated. Thus, GDNF- and GFRalpha1-immunoreactive taste bud cells after denervation vanished following the disappearance of the taste buds and reappeared at the same time as the taste buds reappeared.

Animals↗

Antitumor efficacy of nedaplatin, a novel platinum complex, with cyclophosphamide in murine and human tumor model.

BACKGROUND: The antitumor efficacy of the combination of Nedaplatin (NDP) with cyclophosphamide (CPM) was evaluated using murine and human carcinoma implanted mice. NDP was developed as a second generation platinum complex. Because of its superior antitumor activity and lower nephrotoxicity than Cisplatin (CDDP), we also compared the antitumor activity of NDP plus CPM with that of CDDP plus CPM. MATERIALS AND METHODS: Various doses of NDP or CDDP (1/4 to 1 maximum tolerated dose; MTD) and CPM (58 or 78 mg/kg) were injected once via the tail vein into mice implanted with Lewis murine lung carcinoma or Ma44 human lung carcinoma. RESULTS: Simultaneous administration of NDP or CDDP with CPM resulted in synergistically enhanced inhibition of tumor growth and prolonged survival in comparison with therapy using only NDP, CDDP or CPM. The combination therapy of NDP with CPM showed a superior survival effect with frequent long-term tumor-free survivors in comparison to that of CDDP plus CPM without increased hematotoxicity. The augmented antitumor efficacy of the combination of NDP with CPM was also demonstrated against Ma44 human lung carcinoma. CONCLUSION: The results suggested the effectiveness of using a combination of NDP with CPM for clinical therapy.

Animals↗

Trophic response of gut and pancreas after ileojejunal transposition.

OBJECTIVE: The authors determined whether ileojejunal transposition (IJT) stimulates the growth of the pancreas or the nontransposed segment of small intestine, and ascertained whether this trophic effect is altered by the location of transposed gut segment. SUMMARY BACKGROUND DATA: Transposition of the ileum to the proximal small intestine stimulates a marked mucosal growth of the transposed ileal segment; the cellular mechanisms responsible for this adaptive hyperplasia are not known. METHODS: The distal quarter of the small intestine (distal ileum) was transposed into the proximal (Type I), middle (Type II), or distal (Type III) portions of the remaining small intestine. On postoperative day 28, the pancreas and scraped mucosa from the segments of transposed ileum, proximal ileum, and duodenum were obtained, weighed, and examined for DNA and protein content. RESULTS: All types of IJT increased mucosal weight and DNA content of the transposed ileum. Types I and II IJT produced a significant proliferation of the pancreas and mucosa of the duodenum and proximal ileum. The magnitude of proliferative increases was greatest in Type I IJT. CONCLUSIONS: Ileojejunal transposition appears to be an excellent model to examine the mechanisms by which intestinal epithelial cells proliferate in response to luminal nutrients or humoral factors.

Adaptation, Physiological↗

The importance of the real-time fluoroscopic intraoperative direct cholangiogram in the laparoscopic cholecystectomy using a new instrument.

BACKGROUND/AIMS: Laparoscopic cholecystectomy (LC) has become an accepted standard operative technique for gallstone treatment worldwide. On the other hand, complications, such as bile duct injuries, have been reported recently with the expansion of indication for LC. Intraoperative cholangiogram (IOC), to minimize the risk of bile duct injury, is now considered to be essential for safe LC. There are disadvantages to IOC such as increased operating time, the possibility of bile duct injury and the difficulties of manipulation. MATERIAL AND METHODS: We have developed a method for real-time fluoroscopic cholangiograms using a new instrument designed by our group for safe LC. First, a round-tip stylet is inserted through a sheath to coax it gently through the spiral valves of the cystic duct. Secondly, the stylet is removed and the cholangiogram catheter is inserted smoothly. Digital C-arm fluoroscopy provides "real-time" imaging of biliary tree. As a result, we became able to obtain a clear cholangiogram easily in a very short time. RESULTS: In the first 136 patients, direct cholangiograms were attempted in 106 cases and successfully completed in 102 cases (96.2%). CONCLUSION: With the development of real-time fluoroscopic intraoperative direct cholangiogram, we are able to cope with bile duct injuries and anomalies, and unsuspected bile duct stones.

Adult↗

Quantification of estrogen receptor messenger RNA by quantitative polymerase chain reaction using internal standard fragment.

A simple and reliable polymerase chain reaction-based method for quantifying human and rat estrogen receptor (ER)-mRNA is described. This method involves co-amplification of cDNA transcribed from sample RNA with an internal standard to reduce tube to tube amplification variations. Human and rat internal standards were synthesized by insertion of a DNA fragment near the midportion of human and rat target ER cDNA molecules. After co-amplification, both products of target ER cDNA and internal standard were separated on agarose gel by electrophoresis and transferred onto a membrane filter. The radioactivity hybridized with 32P-labeled ER cDNA was counted. The ER mRNA content was calculated by linear regression analysis after obtaining a logarithm of ratios between the sample and the internal standard radioactivity. The coefficient of variation of this assay was 18.8%. An absolute amount of ER mRNA in less than 10(4) cultured cells could be measured.

Animals↗

Restricted use of T-cell receptor V beta genes in posttransfusion graft-versus-host disease.

BACKGROUND: Posttransfusion graft-versus-host disease (PT-GVHD) is a pathophysiological process of the immune system. Mature donor T cells that have survived the host defense mechanisms recognize recipient allo-antigens through antigen-specific T-cell receptors and mount an immune attack against certain host antigens. STUDY DESIGN AND METHODS: To characterize the T cells involved in PT-GVHD, expression of the T-cell receptor V beta genes in peripheral blood T cells isolated from four PT-GVHD patients was analyzed. T-cell receptor beta chain cDNA derived from mRNA extracted from peripheral blood lymphocytes was amplified by an inverse polymerase chain reaction method, and the cDNA was subsequently cloned and sequenced. RESULTS: The cDNA clones derived from patients with PT-GVHD showed remarkable differences in the distribution of T-cell receptor V beta gene use from that in normal controls. Very restricted T-cell receptor V beta gene repertoires and preferential expression of certain V beta gene segments were revealed in the peripheral blood lymphocytes of each patients. Shared V beta gene use among the patients was not observed, probably because of HLA differences among the patient-donor combinations. CONCLUSION: This restricted use reflected in vivo expansion of a limited number of engrafted T-cell clones at the onset of PT-GVHD and suggested that those oligoclonal donor T cells may be involved in the induction of PT-GVHD.

Aged↗

Herniation of cervical intervertebral disc: immunohistochemical examination and measurement of nitric oxide production.

STUDY DESIGN: Surgically obtained cervical herniated intervertebral discs were examined histologically and immunohistochemically. The production of nitric oxide (NO) in the local tissue was examined using the electron spin resonance (ESR) method. OBJECTIVES: To investigate the local histologic and immunohistochemical changes in cervical disc herniation, including NO production, and to compare such changes with those in autopsy cases. SUMMARY OF BACKGROUND DATA: Very little is known about the histopathologic processes of cervical disc herniation. In addition, no information is available on the level of in vivo NO production in cervical disc herniation. METHODS: Thirty-six herniated cervical discs obtained from 31 patients were immunohistochemically examined for localization of blood vessels, matrix metalloproteinase (MMP)-3, and inducible NO synthetase (iNOS). We also compared the production of NO, measured by the ESR method, in eight specimens with that of five control discs obtained from fresh cadavers. RESULTS: The presence of herniated discs correlated with the degeneration of cartilaginous endplate and torn anulus fibrosus. Formation of new blood vessels around the herniated discs was detected, using von Willebrand factor antibody, in seven uncontained hernias and 20 contained hernias. Immunohistochemical studies showed the presence of cells positive for MMP-3 (chondrocytes), iNOS (chondrocytes and granulation tissue) in cervical disc hernias. ESR analysis showed a significantly higher NO production in herniated cervical discs than in disc samples of fresh cadavers. CONCLUSIONS: Herniated cervical intervertebral disc is characterized by the presence of an inflammatory process associated with neovascularization and increased expression of MMP-3. Production of NO was markedly high in both contained- and uncontained-type hernias.

Adult↗

Percutaneous chronic epidural catheterization in the rabbit.

BACKGROUND: Although several epidural catheterizations in small animals have been reported, all of them were performed surgically and no percutaneous method has been reported. We have established a technique for percutaneous chronic epidural catheterization in rabbits. METHODS: Following pentobarbital anesthesia, the animals (n = 15) were fixed in a prone position using a fixing apparatus. A 19-gauge Tuohy needle was inserted in the lumbar region at an angle of about 30 degrees to the skin with the paramedian approach and advanced into the epidural space with the loss-of-resistance method. A 23-gauge Nylon catheter was advanced cephalad in the epidural space and the distal tip was extruded from the neck following the subcutaneous tunnelling. The effects of 0.5 ml of 1% lidocaine injected through the catheter were observed for 10 days. RESULTS: No behavioral or neurological abnormalities were observed after the catheterization except for one case of catheterization in the epidural vessel. Motor paralysis of hind-limbs became manifest at 1-2 min after injection of 0.5 ml of 1% lidocaine through the catheter, and lasted 15-25 min. Autopsy revealed that the catheter was located in the lumbar epidural space in all animals and the distribution of methylene blue was consistent with that of lidocaine. CONCLUSION: This rabbit model can be used to investigate the effects of epidurally administered drugs.

Animals↗

Effects of airway inflammation on cough response in the guinea pig.

We have developed a guinea pig model for cough related to allergic airway inflammation. Unanesthetized animals were exposed to capsaicin aerosols for 10 min, and cough frequency was counted during this period. The cough evaluation was performed by the following three methods: visual observation, acoustic analysis, and monitoring of pressure changes in the body chamber. These analyses clearly differentiated a cough from a sneeze. To elucidate the relationship between cough response and airway inflammation, animals were immunosensitized and multiple challenged. Sensitized guinea pigs presented no specific changes microscopically, but multiple-challenged animals showed an increased infiltration of inflammatory cells into the airway. Cough number in response to capsaicin increased significantly from 4.7 +/- 1.4 coughs/10 min in normal animals to 10.6 +/- 2.0 coughs/10 min in sensitized animals and further to 22.8 +/- 1.3 coughs/10 min in multiple-challenged animals. This augmented cough frequency was significantly inhibited by the inhalation of tachykinin-receptor antagonists and by oral ingestion, but not inhalation, of codeine phosphate. The results suggest that airway inflammation potentiates an elevation of cough sensitivity in this model.

Animals↗

Mechanisms for the aging-induced reduction of lead solubility in scrubber residues from municipal solid waste combustion.

This manuscript elucidates the mechanisms responsible for aging-induced reduction in lead leaching from scrubber residues. Leaching tests (JLT13) were conducted on 48 types of scrubber residues and lead solubility was found to be significantly reduced independent of incinerator type or type of gas treatment method. Reaction kinetics that result in lead solubility reduction were shown to be proportional to carbon dioxide partial pressure and in many cases were limited by mass transfer to the residue. With forced gas convection through the residue and a CO2 partial pressure of 0.3%, the concentration of lead in leachate was reduced from 84 mg L(-1) to < 0.5 mg L(-1) in two days. Ettringite analogs (Ca6Al2 (SO4) 3(OH)2 . 26H2O) were identified by X-Ray Diffraction in the wetted scrubber residues early in the aging process; these appear to have been converted into gypsum (CaSO4 . 2H2O) and vaterite (CaCO3) in the aged material. All of these solid phases are believed to substitute lead into their crystal structure and evidence for this attenuation mechanism is presented.

Air Pollution↗

Molecular cloning, characterization, and expression in Escherichia coli of a cDNA encoding mammalian choline kinase.

A rat liver lambda gt11 cDNA library was screened with antibody against rat liver choline kinase. One of the putative phage clones obtained was found to express choline kinase activity in infected Escherichia coli cells and used for the isolation of fully extended cDNA clones by hybridization. The obtained clones had identical overlapping nucleotide sequences and gave a composite cDNA sequence of 2540 bases. Poly(A)+ tails were found at three different sites of the cDNA sequence. Within the sequence there was a large open reading frame encoding 435 amino acids with a molecular mass of 49,743 Da. When this open reading frame was placed after the trc promoter and introduced into E. coli cells, fully active choline kinase was produced. This enzyme was partially purified using a published choline kinase purification method and was found to mediate the phosphorylation of choline, N,N-dimethylethanolamine,N-monomethylethanolamine, and ethanolamine. Similar to the case with choline kinases from various sources, Km decreased as the number of N-methyl groups increased. The deduced amino acid sequence significantly resembled the yeast choline kinase sequence. It also showed local sequence similarity to protein kinases and some bacterial phosphotransferases. Northern blot analysis revealed that the cDNA probe hybridized to 2.8- and 1.8-kilobase RNA in various rat tissues. The sizes of the transcripts were fairly consistent with that of cDNA. The order of mRNA abundance was testis, brain, lung, kidney, and liver, but did not coincide with the order of the activity levels in these tissues. These results show that the cloned cDNA encodes one of the choline kinase isoforms present in mammalian tissues.

Amino Acid Sequence↗

A new evaluation of pancreatic function after pancreatoduodenectomy using secretin magnetic resonance cholangiopancreatography.

BACKGROUND: The remnant pancreatic function after pancreatoduodenectomy influences greatly postoperative quality of life. However, it has been difficult to evaluate the exocrine remnant pancreatic function postoperatively. The aim of this study was to assess the usefulness of secretin-stimulated magnetic resonance cholangiopancreatography (secretin MRCP) in evaluating the remnant pancreatic function and ascertaining the anastomotic patency after pancreatoduodenectomy. METHODS: Thirty-four patients who underwent pancreatoduodenectomy were evaluated with secretin MRCP. The results of MRCP were determined by the amount of exocrine pancreatic secretion, and were graded as follows: grade I (poor secretion), grade II (moderate secretion), and grade III (good secretion). RESULTS: Secretin MRCP could visualize the pancreatic secretion dynamically. MRCP grades were grade I in 11 patients, grade II in 12, and grade III in 11. There was a significant correlation between MRCP grade and glucose tolerance. We confirmed visually the patency of the anastomotic site in 24 patients (71%). MRCP grades correlated significantly with clinical symptoms. CONCLUSION: Our results demonstrated secretin MRCP was feasible for evaluating the remnant pancreatic function after pancreatoduodenectomy.

Adult↗

[Radial flap: a valuable fasciocutaneous flap for intra-oral reconstruction].

The radial forearm flap, or the forearm flap, is called "Chinese flap" for its development of the chinese doctors, and is originally designed for the correction to the post-burn contraction of the face and neck. The radial forearm flap is one of the fasciocutaneous flap, supplied by the radial artery, and transferred as a single-stage reconstruction micro-surgically. In oral and maxillofacial region, the deltopectral flap (D-P flap) and the pectralis major myocutaneous flap (P-M-M-C flap) are mainly used for the reconstruction. These flaps, however, are sometimes too bulky and limited to transfer, and more require two-stage operations. On the other hand, as the forearm flap being thin and pliable, some doctors use this flap micro-surgically at single-stage free flap reconstruction. Before two years, we have begun to transfer the radial forearm flap for the intra-oral reconstruction. The operation method is as follows. Design and Elevation of the Radial Forearm Flap 1. Using the ultrasonic doppler flow meter, the radial artery and the subcutaneous forearm veins are marked on the skin. 2. The flap is designed 20% larger according to the pattern to be reconstructed, with the distal section of the radial artery as an axis on the forearm and the median vein of forearm inclusively. 3. Before the operation, Allen test must be performed in order to determine whether the hand will survive without a radial arterial in-put. 4. The operation is performed with a arm tourniquet. The margin of the flap are incised down to the deep fascia, isolating and preserving the proximal subcutaneous veins as required.(ABSTRACT TRUNCATED AT 250 WORDS)

Forearm↗

Lymph node metastases detected in the mesorectum distal to carcinoma of the rectum by the clearing method: justification of total mesorectal excision.

BACKGROUND: Total mesorectal excision effectively reduces the local recurrence rate of carcinoma of the rectum. This study was undertaken to clarify the rationale for total mesorectal excision. STUDY DESIGN: We retrospectively reviewed the records of 198 patients who underwent resection of a carcinoma of the rectum. The presence of nodal metastases in the mesorectum distal to the primary tumor was examined by the clearing method. RESULTS: The metastatic rate in the distal mesorectum was 20.2 percent. The metastatic rates according to the extent and site of the tumor were as follows: pT1, 0 percent; pT2, 0 percent; pT3, 21.9 percent; pT4, 50 percent; rectosigmoid, 10 percent; upper rectum, 26.3 percent; and lower rectum, 19.2 percent. The longest distal spread from the primary tumor to the metastatic node was 2 cm in carcinoma of the rectosigmoid, 4 cm in carcinoma of the upper rectum, and 3 cm in carcinoma of the lower rectum. CONCLUSIONS: Total mesorectal excision is required for patients with T3 and T4 tumors in the lower rectum, and excision of all mesorectal tissue down to at least 5 cm below the tumor is required for patients with T3 and T4 tumors in the upper rectum.

Humans↗

Combined transjugular intrahepatic portosystemic shunt and segmental Lipiodol hepatic artery embolization for the treatment of esophagogastric varices and hepatocellular carcinoma in patients with cirrhosis: preliminary report.

PURPOSE: To evaluate the feasibility of combining placement of a transjugular intrahepatic portosystemic shunt (TIPS) and transcatheter hepatic segmental artery chemoembolization with Lipiodol (Seg-Lp-TAE) in patients with cirrhosis, esophagogastric varices, and hepatocellular carcinoma (HCC). METHODS: Five patients with bleeding or large, high-flow esophagogastric varices and HCC were treated by TIPS and Seg-Lp-TAE. RESULTS: The mean portosystemic pressure gradient decreased from 20.8 cm H2O to 7.8 cm H2O after TIPS. The direct portogram and endoscopic examination revealed reduction of varices. At 6 months, one shunt had functionally occluded and could not be reopened; the other TIPS remained functional. Follow-up CT and the changes of alpha fetoprotein indicated effective therapy of Seg-Lp-TAE for HCC. Four patients are in stabile clinical condition at 9, 6, 1, and 1 months after the combined therapy; one died after 14 months due to decompensated liver cirrhosis. CONCLUSION: The combined therapy of TIPS and Seg-Lp-TAE will become a new interventional approach for patients with HCC and esophagogastric varices.

Aged↗

Serum cystatin C concentration as a marker of glomerular filtration rate in patients with various renal diseases.

OBJECTIVE: The present study was undertaken to evaluate clinical application of serum cystatin C as a new marker of glomerular filtration rate (GFR) in patients with various renal diseases. PATIENTS AND METHODS: A total of 140 patients were enrolled in the study. We measured the serum cystatin C levels and compared them with creatinine clearance (Ccr) and inulin clearance (Cin) as an indicator of GFR. RESULTS: There was a significant positive correlation between serum cystatin C and creatinine levels (r=0.928). Serum cystatin C was inversely correlated with creatinine clearance. Moreover, the reciprocal serum cystatin C level was positively correlated with Cin (r=0.882). The receiver-operating characteristic curve of serum cystatin C and creatinine demonstrated that the diagnostic accuracy of the serum cystatin C level is superior to that of creatinine in identifying individuals with reduced GFR. CONCLUSION: These results indicated that measurement of serum cystatin C is useful to estimate GFR, and in particular, to detect a mild reduction of GFR in patients with renal diseases.

Adult↗