Dieulafoy lesion in a congenital double pylorus.
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Aged↗
Biomedical subjects
G Schwab
Publications and source records attributed to G Schwab.
An approach for new anticancer drugs: oncogene-targeted antisense DNA.
BACKGROUND: Ras oncogenes owe their transforming properties to single point mutations in the sequence coding for the catalytic part of the p21 protein. These mutations lead to changes in cellular proliferation and tumorigenic properties. Point mutations represent a defined target for antisense oligonucleotides which specifically suppress translation of the targeted mRNA. However, the use of oligonucleotides in vivo has, until now, been limited by their instability in serum. NEW TECHNIQUES: Different strategies have been developed to protect the oligonucleotides and increase their transport into the target cell. Linking intercalating agents, hydrophobic groups or polycations to oligonucleotides or encapsulating them in liposomes resulted in a higher resistance to exonucleases and increased oligonucleotide penetration into cells. The stability and cellular uptake of antisense oligonucleotides can also be improved by associating them with polyalkylcyanoacrylate nanoparticles. The polymeric nature renders these small particles more stable than liposomes in biological fluids and during storage. METHOD: Antisense oligonucleotides directed to the point mutation (G to T) in codon 12 of the Ha-ras mRNA were adsorbed to nanoparticles in the presence of hydrophobic cations. RESULTS: These stabilized oligonucleotides selectively inhibited the proliferation of cells expressing this point mutation and partially reversed their tumorigenicity in nude mice.
Antineoplastic Agents↗
Traumatic bilhemia.
BACKGROUND: Retrospective analysis was done of three cases with severe liver trauma and excessive serum bilirubin levels caused by a traumatic biliovenous fistula. The literature is reviewed. METHODS: Diagnostic measures included laboratory findings, computed tomography, ultrasonography, and endoscopic retrograde cholangiopancreatography (ERCP). RESULTS: The biliovenous fistula was detected by ERCP in two cases. In one case a left hemihepatectomy was carried out, and the patient was cured. The other patient received drainage of a huge necrotic cavity in the center of the liver. Ten months later the patient underwent reoperation, and left hepatic resection was performed. The patient died of liver function failure on postoperative day 7. In the third case the fistula subsided spontaneously. CONCLUSIONS: An excessively high serum level of direct bilirubin and only moderately elevated liver enzymes indicate bilhemia in trauma patients. ERCP is most reliable in localizing the fistula; computed tomography/ultrasonography are valuable in detecting the extension and localization of the parenchymal destruction. Conservative therapy is justified if the patient is in good condition or if the localization of the fistula is unclear. Spontaneous closure of the fistula may occur. Surgical treatment options are partial liver resection and suture of the fistula and T-tube drainage of the common bile duct and drainage of the rupture site.
Adolescent↗
Retropneumoperitoneum: an unusual case after colonoscopy.
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Aged↗
Benzoquinonoid ansamycins possess selective tumoricidal activity unrelated to src kinase inhibition.
The benzoquinonoid ansamycin antibiotics herbimycin A and geldanamycin have been shown to reverse the oncogenic phenotype of pp60v-src transformed cells as well as induce differentiation in a number of in vitro model systems, reportedly due to their inhibition of src family protein tyrosine kinases. We now report that these agents are potent cytotoxins in vitro against a panel of highly malignant human tumor cell lines possessing primitive neural features. Proliferation and/or survival of fibroblasts, primary neuronal cultures, and several leukemia cell lines are unaffected at concentrations resulting in greater than 99% cell loss in sensitive lines. The tumorigenicity in nude mice of sensitive cell lines can also be markedly reduced by either systemic or topical administration of these agents without apparent toxicity to the whole animal. The cytocidal action of these ansamycins is initiated very rapidly, is irreversible, and is clearly distinct from the delayed inhibition of src family kinases that has been reported previously. Due to their potency, relative selectivity, and novel mechanism(s) of action, these drugs could prove clinically useful in the therapy of a number of human cancers of neural derivation.
3T3 Cells↗
Incarcerated bariolith of the cecum eight months after a barium meal.
Barioliths consist of inspissated barium mixed with feces. They are a rare complication after barium contrast roentgenography and occur almost exclusively in the large bowel. Mostly asymptomatic or causing only slight symptoms and signs, they may persist for months or years. We report a severe case of cecal bariolith. Clinical symptoms and signs, radiological findings, intraoperative findings, and histology are presented and discussed with reference to the literature.
Aged↗
Primary squamous cell carcinoma of the stomach in a seventeen-year-old boy.
Primary squamous cell carcinoma (SCC) of the stomach is extremely rare and thought to arise from ectopic squamous epithelium, which in turn could either result from the squamous metaplasia of the gastric mucosa or be congenital in origin. We report herein a case of SCC of the stomach in a 17-year-old male, who died 1 year after undergoing a gastrectomy. To our knowledge, this is the youngest case of primary SCC of the stomach reported in the literature. Further speculative possibilities of the development of primary gastric SCC are discussed following the presentation of this case.
Adolescent↗
[Subcutaneous gas emphysema as an intraoperative complication in laparoscopic laser cholecystectomy].
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Adult↗
Treatment of calculi of the common bile duct.
Endoscopic sphincterotomy (EST) is regarded as an alternative therapeutic approach to the surgical treatment of choledocholithiasis. To clarify the indication for each of these two methods, a prospective study has been performed comparing patients with calculi of the common bile duct who had undergone endoscopic or surgical treatment. Mortality, morbidity and stone clearance were used as criteria for the evaluation of the dependence of age on results achieved by the two modalities. Of 306 patients with choledocholithiasis, 199 underwent surgical exploration of the duct and 107 underwent endoscopic sphincterotomy. Patients who were more than 60 years of age and had previously undergone cholecystectomy underwent endoscopic sphincterotomy. All other patients had surgical treatment. There were no significant differences among the two groups with regard to mortality rates. The incidence of relevant complications as well as the incidence of surgical revisions related to postoperative complications in the operation group was, however, significantly higher (p less than 0.05). In contrast with this, the incidence of retained stones was significantly lower (p less than 0.01) in the group that underwent surgical treatment (2.5 percent) than in the group that had endoscopy (11.2 percent). When assessing the results in terms of stone clearance, complications and mortality rates, findings seem to indicate that a safe limit for the application of surgical treatment would be 60 years of age, whereas older patients should be primarily considered as candidates for EST.
Age Factors↗
Characterization of an interleukin-6-mediated autocrine growth loop in the human multiple myeloma cell line, U266.
It has been reported recently that freshly isolated human myeloma cell cultures proliferate in response to added interleukin-6 (IL-6). Endogenous levels of IL-6 found in the same cultures suggested that an autocrine growth loop may contribute to cell growth. However, the lack of homogenous cell populations in primary myeloma cultures has made it difficult to distinguish between paracrine and autocrine growth mechanisms. To precisely address the autocrine growth issue we have evaluated the growth of the human myeloma cell line, U266. We have found that a neutralizing anti-IL-6 monoclonal antibody can inhibit U266 proliferation. Furthermore, the addition of IL-6 antisense oligonucleotides also inhibits U266 proliferation. These effects are reversed by adding IL-6, suggesting the presence of an autocrine loop. Using bioassays with two different IL-6-dependent cell lines, we were able to detect IL-6 in concentrated U266 supernatants. IL-6 mRNA was detected by polymerase chain reaction amplification of cDNA. Cell cycle parameter analysis shows that IL-6 acts to release a block in G1. Taken together these results present conclusive evidence for IL-6-mediated autocrine growth in the U266 human myeloma cell line.
Base Sequence↗
Quantitative nuclear DNA content in fine needle aspirates of pancreatic cancer.
The quantitative nuclear DNA content of nuclei from fine needle aspirations from 70 patients with pancreatic cancer was measured using an image analyser system. Retrospective analysis of patients indicated that cases with tumour stemlines in the diploid region had the best chance for radical surgery (p less than 0.006) and the best probability of survival (p less than 0.0004). The prognosis for patients with tetraploid stemlines was intermediate and was poorest for patients with no stemlines in the diploid-tetraploid region. From those parameters assessed postoperatively, only the tumour stage added appreciable information on prognosis to the preoperative quantitative DNA content obtainable. Therefore, in patients with pancreatic cancer the quantitative DNA content should be taken into account in planning treatment and assessing prognosis. Furthermore, the quantitative DNA content may have a major role in stratification for further treatment trials.
Adult↗
Combined extracorporeal shock wave lithotripsy and laparoscopic cholecystectomy.
For many centers, laparoscopic cholecystectomy (LC) has become the treatment of choice in cholecystolithiasis. Sometimes, however, bile stones with a diameter of 1.5 cm and above can only be removed if the periumbilical incision is enlarged or the stone is crushed with a forceps intraoperatively. To keep the incision as small as possible, to be able to work with the smallest available trocars, and to shorten the operative procedure, patients in our center with stones larger than 1.5 cm are submitted to preoperative extracorporeal shock wave lithotripsy (ESWL). LC is performed the same or the next day. We have used this procedure in eight patients, and LC could be performed in all cases without enlargement of the periumbilical incision. Macromorphological changes of the gallbladder following ESWL, such as hematoma and edema, were not seen.
Cholangiography↗
Expression of the interleukin 6 receptor and interleukin 6 in prostate carcinoma cells.
We have probed for the presence of interleukin 6 (IL6) receptors in prostatic carcinoma cell lines (LNCaP, DU 145, and PC3) by examining their sensitivity to the cytotoxic effects of a chimeric toxin composed of IL6 and Pseudomonas exotoxin (PE). All three cell lines were killed by IL6-PE66(4)Glu, a version of IL6-PE in which the binding domain of native PE has been mutated to debilitate PE binding to its own receptor. This cytotoxic activity confirmed the presence of IL6 receptors on prostatic carcinoma cells. We have measured the number of IL6 receptors found on these cells and have further determined that they secrete IL6. These data provide evidence that IL6 and its receptor may play an important role in human prostate cancer.
ADP Ribose Transferases↗
Nuclear DNA distribution pattern of the parenchymal cells in adenocarcinomas of the pancreas and in chronic pancreatitis. A study of archival specimens using both image and flow cytometry.
The nuclear DNA distribution pattern of the neoplastic parenchymal cells of 100 conventionally formalin-fixed and paraffin-embedded specimens from pancreatic adenocarcinomas and from 8 specimens of chronic pancreatitis was assessed by means of image cytometry. All material originated from pancreatic restrictions. Evaluable DNA histograms could be obtained for 77 carcinomas, and clinical data were available for 71 of these. In these 71 specimens, the nuclear DNA ploidy pattern was also investigated by means of flow cytometry. In 76 of the 77 cases, the image-cytometric DNA ploidy pattern obtained showed a "nondiploid" distribution with modal values as high as 8.5 c. In 21 cases, the neoplastic cells showed modal values in the "triploid" region. The analogous 71 flow-cytometric DNA histograms could only be evaluated in 50 cases because of excessively high amounts of background and/or excessively broad peaks. In 47 cases, the nuclear DNA histogram was nondiploid according to both techniques. The patients with carcinomas whose cell nuclei showed a triploid DNA distribution showed a significantly shorter survival time than those with tumor cell populations of nontriploid DNA distribution patterns. In the 8 specimens of chronic pancreatitis, the parenchymal cells were all equipped with nuclei showing diploid DNA distribution patterns.
Adenocarcinoma↗
[Peptic ulcer with a visible non-bleeding vascular wall--early elective surgery or endoscopic therapy?].
The records of 71 patients with the endoscopic finding of a peptic ulcer with a non-bleeding visible vessel, treated between 1982 and 1987 were retrospectively analysed. 16 patients underwent early surgical treatment (group I), 15 patients were treated conservatively (group II) and 40 patients by endoscopic haemostasis (group III). Recurrent bleeding was observed in 6.25% patients in group I, in 53.3% in group II and in 25% in group III, in which case endoscopy was performed again. The patients with arterial bleeding underwent early elective operation after endoscopic haemostasis. Deaths occurred only in the postoperative period: group I 6.25%, group II 13%, and group III 5%. These findings indicate that primary endoscopic treatment in selected patients leads to results equal to those achieved with early surgery. Conservative therapy cannot, however, be recommended.
Adult↗
[Tumor markers in the upper intestinal tract--stomach and pancreas].
Expectations of early diagnosis of carcinoma of the stomach and pancreas by using the tumour markers CEA and CA 19-9 have been disappointed. Although the sensitivity of CA 19-9 for pancreatic cancer is high, its field of application for screening is not efficient due to poor specificity of the marker. CEA and CA 19-9 are of great importance in the follow-up of pancreatic cancer. Results of tests of CEA and CA 19-9 in 100 patients with gastric cancer and 50 patients suffering from pancreatic cancer are reported.
Antigens, Tumor-Associated, Carbohydrate↗
High frequency of Ki-ras codon 12 mutations in pancreatic adenocarcinomas.
The frequency of Ki-ras gene mutations was studied in 100 paraffin-embedded sections obtained from 63 pancreatic adenocarcinomas by in vitro amplification of target sequences via polymerase chain reaction (PCR) and selective oligonucleotide hybridization. Forty-seven (75%) of the tumors contained a Ki-ras mutation at codon 12. No predominant amino acid substitution or nucleotide transition at this codon was observed. Two carcinomas exhibited 2 distinct Ki-ras mutations. No particular correlation could be established between the incidence of Ki-ras mutation and clinical parameters (sex, age, survival), tumor grade or tumor stage.
Adenocarcinoma↗
Methodological aspects of DNA image cytometry in formalin-fixed paraffin-embedded material from pancreatic adenocarcinoma.
Deparaffinized and disintegrated material from conventionally formalin-fixed and paraffin-embedded surgical specimens of 100 cases of ductal adenocarcinoma of the pancreas was Feulgen-stained, and the cytochemical DNA distribution patterns of at least 100 single tumour cells and 50 "control" cells (fibrocytes) were assessed by means of image cytometry (ICM). In 77 cases a sufficient number of neoplastic cells could be obtained for these DNA assessments. The fairly high number (23) of cases that had to be excluded due to too small amounts of disintegrated cells or cell nuclei may be explained by the high content of connective tissue stroma in these pancreatic adenocarcinomas. The tumour cell nuclei in 76 of these 77 cases showed cytochemically a clear-cut "non-diploid" DNA distribution pattern. This observation reflects the well-known highly malignant growth potential of this carcinoma. Despite the fact that about 1/4 of the tumours had to be excluded, the main result of our methodological study is, after all that conventionally formalin-fixed paraffin-embedded specimens of most pancreatic adenocarcinomas can be successfully used for the deparaffinization-disintegration procedure preceding the nuclear DNA assessments by means of ICM. Additional studies are, however, required to obtain the diagnostic and prognostic impact of the results of such cytochemical analyses of the DNA distribution pattern in adenocarcinomas of the pancreas.
Adenocarcinoma↗