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Biomedical subjects

H Lang

Publications and source records attributed to H Lang.

At least 55 records · Page 3Linked to original sources

[Liver resection and liver transplantation in liver cell adenoma, hepatocellular carcinoma and fibrolamellar liver carcinoma].

Hepatocellular adenomas are rare benign conditions but represent an indication for resection due to their risk of rupture and malignant mutation. Surgical resection should include a safety margin according to oncologic principles. Surgical resection does represent the optimal treatment modality for hepatocellular carcinoma without accompanied cirrhosis of the liver. The rare fibrolamellar carcinoma has the best prognosis. Liver transplantation is usually not performed in HCC without cirrhosis. In case of HCC with cirrhosis in stage I and II the relapse free 5-year-survival rate is more than 50% after liver transplantation. In the UICC-stages III and IV the results of liver transplantation are worse, which points to the impact of exact preoperative staging. Liver resection in HCC and cirrhosis is indicated in stage I and II in case of good liver function. In case of liver resection the survival rates are worse with significantly higher relapses compared to liver transplantation. For small, functionally irresectable hepatocellular carcinoma in cirrhosis liver transplantation is the treatment of choice today.

Adenoma, Liver Cell↗

[Ex situ resection and resection of the in situ perfused liver: are there still indications?].

Most liver tumors can be removed with conventional resection techniques employing partial or total vascular occlusion when needed. Duration of tolerable warm ischemia has not yet been defined, but it seems to be well tolerated up to 60 min. In a few cases with extended vascular resection and reconstruction liver protection by hypothermic perfusion is advantageous. This can be achieved by in situ perfusion, ante situm resection or ex situ resection. Major reconstruction of hepatic vessels with good technical access should be performed under in situ hypothermic protection using veno-venous bypass. Tumors involving the hepatic venous confluence and/or retrohepatic vena cava should be approached by either the in situ, or preferentially, the ante situm resection technique. The indication for an ex situ liver resection resulting in autotransplantation of the remnant liver exists only in rare cases for oncological reasons.

Adult↗

[Donor risk in living-related liver transplantation - the surgeon's point of view].

Living-related liver transplantation is a successful clinical approach to overcome organ shortage in hepatic transplantation. Possible advantages for the recipient of a living-donor transplant are a much shorter waiting period until transplantation and an almost elective time of operation which results in a decreased operative risk. Furthermore graft function of a living-related transplant is better than in cadaveric transplantation because of the shorter ischemic time and a careful examination of graft quality before organ donation. Removal of even more than 50 % of liver volume during the donor operation does not lead to an impairment of liver function in the organ donor. Intraoperative blood loss can usually be managed by re-transfusion of donor's own blood. Postoperative morbidity is about 10 - 15 % depending on the extent of the removed liver lobe. Most frequent postoperative complications are biliary leckages, wound infections and gastric/duodenal ulcerations. Up till now in more than 1000 living-related liver donations only three deaths occured due to thromboembolic and septic complications (< 0,3 %) (until 12/1998).

Humans↗

Surgery as primary treatment in patients with liver metastases from carcinoid tumors: a retrospective, unicentric study over 13 years.

BACKGROUND: The heterogeneous nature of carcinoid tumors makes it difficult to develop a standardized treatment strategy for the primary tumor itself and for probable liver metastases. However, prolongation of the 5-year survival rate (5-ysr) and amelioration of the incapacitating symptoms after resection of the primary tumor and its metastases demonstrate that surgical intervention must be the treatment of choice in these tumors. METHODS: The data of 31 patients (17 patients with midgut carcinoids, 10 patients with an endocrine carcinoma (carcinoid) of the pancreas, and 4 patients with carcinoids of the lung) who underwent liver operation for metastatic carcinoid tumors between 1983 and 1996 were analyzed, with special regard to factors influencing postoperative survival. RESULTS: Ten patients underwent curative resection (5-ysr, 86%), and palliative operations were performed in 21 patients (5-ysr, 26%). The overall 5-ysr was 47%, with a mean postoperative follow-up of 3.5 years (range, 4 months to 10.8 years). Postoperative morbidity rate was 13%. Size of liver metastases, radicality of the operation and localization of the primary tumor were factors influencing postoperative survival. CONCLUSIONS: Surgery for metastatic carcinoid tumors may be curative or palliative, with a potential for cure in some cases and prolongation of survival and amelioration of symptoms in the majority of patients.

Adult↗

Characterization of a G protein-coupled receptor for nicotinic acid.

Nicotinic acid is a lipid-lowering agent widely used to treat hypertriglyceridemia and to elevate low high density lipoprotein levels. However, the underlying mechanisms are poorly understood. In this study, G protein activation by nicotinic acid and derivatives was assessed as stimulation of guanosine 5'-(gamma-[(35)S]-thio)triphosphate ([(35)S]GTPgammaS) binding, and [(3)H]nicotinic acid was used for specific labeling of binding sites. Nicotinic acid (EC(50) approximately 1 microM) stimulated [(35)S]GTPgammaS binding in membranes from rat adipocytes and spleen, but not from other tissues. G protein activation in adipocyte membranes in the presence of maximally activating concentrations of the selective A(1) adenosine receptor agonist 2-chloro-N(6)-cyclopentyladenosine and nicotinic acid was almost additive, indicating that G proteins of mostly distinct pools were activated by these agonists. G protein activation by nicotinic acid and related substances in spleen and adipocytes revealed identical pharmacological profiles. [(3)H]Nicotinic acid specifically detected guanine nucleotide-sensitive binding sites of identical pharmacology in adipocyte and spleen membranes. The site of action of nicotinic acid is distinct from other G protein-coupled receptors. These data indicate that nicotinic acid most probably acts on a specific G protein-coupled receptor.

Adenylyl Cyclase Inhibitors↗

High expression of the proliferation and apoptosis associated CSE1L/CAS gene in hepatitis and liver neoplasms: correlation with tumor progression.

The CSE1L/CAS protein (CAS) is a Ran-binding protein with a function as nuclear transport (export) factor. Like recently observed for ran and other ran-binding proteins, CSE1L/CAS simultaneously plays a role in the mitotic spindle checkpoint, which assures genomic stability during cell division. This checkpoint is frequently disturbed in neoplasias of various origin, including hepatic tumors. We have evaluated by immunohistology the expression of CAS in adult and embryonic liver, hepatitis, and in liver hyperplasias. Normal hepatocytes revealed no CAS expression while embryonic liver showed strong expression in all parenchymal cells. Bile ducts stained positive with anti-CAS antibodies, and strong CAS expression was also detected at the interface between bile ducts and hepatocytes under conditions associated with regenerative proliferation. The localization of these CAS expressing cells correlated with the distribution of putative liver stem-cells. In active viral (but not in inactive) hepatitis, strong hepatocytal CAS expression correlates in site and intensity with degree of inflammation. Neoplastic liver demonstrated different degrees of CAS expression: no remarkable expression in adenomas, moderate expression in a narrow rim of hepatocytes and in periseptal cholangiolar proliferations in focal nodular hyperplasia, and strong CAS expression in hepatocellular carcinoma. Less differentiated tumors stain stronger than well differentiated. Cholangio-cellular carcinomas show even stronger CAS expression than hepatocellular carcinomas. Our observation of strong expression of CAS in liver cells that are committed for proliferation among them possibly liver stem cells, and in liver neoplasms, is consistant with the fact that CAS functions not solely as a nuclear transport factor but that it is also essential for cell proliferation, particularly for the mitotic spindle checkpoint. Interestingly, genomic instability is frequently observed in hepatic tumors which we have shown here to express large amounts of CAS. Since the degree of CAS-expression correlates with the grade of tumor dedifferentiation, we suggest that CAS should also be further investigated as prognostic marker for hepatic neoplasms.

Adult↗

[Effect of cholesterol deficiency on the membrane fluidity of Jurkat T lymphocytes].

The mechanism of cholesterol deficiency on inhibiting the proliferation of T lymphocytes was investigated on cell membrane fluidity by using fluorescence polarization measurement, 3H-TdR incorporation test and flow cytometer analysis in Jurkat cells, in order to clarify the importance of cholesterol in maintaining the normal function of lymphocytes. The results showed that cell membrane fluidity was increased, cell proliferation was inhibited and blocked on G0/G1 phase in Jurkat cells after being cultured with lovastatin (an inhibitor of rate limiting enzyme for cholesterol synthesis) for 3 days. When the cells were treated with LDL. The changes could be partially buffered. These results suggest that the change of membrane fluidity may be caused by cholesterol deficiency on the proliferation of Jurkat cells.

Anticholesteremic Agents↗

[Post-traumatic rupture in ureteropelvic junction obstruction syndrome: two case reports].

Post-traumatic rupture of UPJ obstruction is a rare event, with few reported cases in the literature. Diagnosis is suggested on imaging studies, especially US and CT findings. The presence of an anterior pelvic hematoma associated with thinning of kidney parenchyma, very distended pelvis and non dilated ureter is suggestive of pre-existing pathology.

Adolescent↗

[Sequencing of E2 gene and comparison analysis of four strains hog cholera virus (HCV)].

Four cDNA fragments of envelope glycoprotoin E2 gene of SM strain, HCLV strain, F03 strain and F07 strain were amplified respectively with RT-PCR method. The amplified E2 fragments of four HCV strains were all 1273 bp in length by agarose gel electrophoresis. Four E2 fragments were cloned respectively into pGEM-T easy vector. 1273 bp cDNA fragment of Four HCV E2 gene were sequenced and 381 residues amino acid sequence of E2 glycoprotein were deduced. The signal peptide sequence (WLLLVTGA) located in the N-terminal residues 683-690 and the transmenbrane region (TMR) sequence located in the C-terminal residues 1031-1063 of Four E2 gene were highly conserved and hydrophobic region. The conserved sequence among the E2 protein of pestiviruses, RYLASLH which located in the N-terminal residues 753-759 of domains B and C, was hydrophilic, and none of them were variable among the pestiviruses, and the greatest values of antigenic in all E2 antigenic domain. This suggest that the conserved sequence RYLASLH are involved in E2 epitopes. The number and locations of 15 cysteine residues in E2 are conserved among pestiviruses, suggesting that the structure of this glycoprotein is similar in pestiviruses and the first six cysteines are critical for the correct folding of E2 and essential for all identified epitopes. It is showed epitopes. between HCLV strains and field strains are not variable obviously by analysising the varintion of some main amino acid residuse substitutions of E2 major antigenic domains.

Amino Acid Sequence↗

Synthesis and reaction of the novel complex [AsPh4][OsCl5(H2O). X-ray structure analysis of [AsPh4][OsCl5(H2O)].2EtOH and [AsPh4][OsCl5(EtOH)].EtOH.

The synthesis and characterization of the anionic mononuclear and homobinuclear osmium complexes [AsPh4][OsCl5L].xEtOH [L = H2O, x = 2 (9); L = EtOH, x = 1 (10a); L = py, x = 0 (10b)] and [AsPh4]2[Cl5Os(pyz)OsCl5] (12) (pyz = pyrazine) are described. Upon reduction in a chloride-containing medium, OsO4 (1) affords the osmium(IV) species [OsCl5(H2O)]- (2), which could be isolated by extraction with n-tributyl phosphate (TBP). Complex 9 is the first fully characterized chloroaquo complex of Os(IV). This complex is an effective starting material for the preparation of novel species, such as 10a, 10b, and 12. The X-ray structures of 9 and 10a were determined. Both compounds crystallize in the monoclinic space group P2(1)/n. 9: C28H34AsCl5O3Os, a = 10.910(4) A, b = 17.127(5) A, c = 17.555(7) A, beta = 103.77(2) degrees, V = 3186(2) A3, and Z = 4. 10a: C28H32AsCl5O2Os, a = 10.7762(2) A, b = 17.3939(1) A, c = 17.1477(3) A, beta = 103.645(1) degrees, V = 3123.45(8) A, and Z = 4. Complexes 9 and 10a crystallize with two and one molecule of EtOH and are bonded via hydrogen bridges to the H2O and EtOH ligand in 9 and 10a, respectively.

Journal Article↗

Evaluation of microsatellite analysis in urine sediment for diagnosis of bladder cancer.

Alterations at microsatellite DNA markers in cells exfoliated in urine have been correlated to the presence of bladder cancer. To check the feasibility of such noninvasive analysis to routinely diagnose bladder cancers, we have developed a highly sensitive method using fluorescent PCR to search for DNA microsatellite alterations in urine sediment compared with a blood paired sample. One hundred eighty-three patients were included in our study. This population comprised 103 bladder cancers (64 pTa stages), the complement representing controls and other benign or malignant diseases. Results of the analysis at 17 loci in a blinded study were compared with cystoscopy and/or pathology. The high reproducibility of this technique and the analysis of 26 control patients allowed us to determine for each microsatellite a cutoff characterizing a significant allelic imbalance. For bladder cancer detection, the overall sensitivity of the test was 84%. Using this procedure, we identified alterations in 81%, 84%, 91%, and 100% of pTa, pT1, pT2, and >pT2 stages, respectively. This corresponds to 79%, 82%, and 96% sensitivity for grades I, II, and III, respectively. Interestingly, for routine purposes, we observed an overall sensitivity of 80% (76% for pTa stages) when only the eight most rearranged microsatellites were considered. In conclusion, the noninvasive feature combined with the rapidity of this fluorescent and highly sensitive technique for the detection of early stages provides us with a useful help for the diagnosis of bladder cancer.

Adolescent↗

Cell proliferation and cell death in the developing chick inner ear: spatial and temporal patterns.

Morphogenesis of the inner ear is a complex process in which the balance of cell division and death is presumed to play an important role. Surprisingly, there are no reports of a systematic comparison of these two processes in individual ears at different stages of development. This study presents such an analysis for the chicken otocyst at stages 13-29 (embryonic days 2.5-6). To detect proliferating cells, we used exposure to bromodeoxyuridine. To detect apoptotic cells, we used nuclear condensation and fragmentation or terminal dUTP nick-end labeling (TUNEL). The spatial and temporal locations of proliferating and dying cells were mapped across serial sections, revealing regional differences in proliferation within the otocyst epithelium that are more complex than previously reported. In addition, almost all of the previously identified "hot spots" of cell death correspond spatially to regions of reduced cell proliferation. An exception is the ventromedial hot spot of cell death, which is intermingled with proliferating cells when it first appears at stages 19-23 before becoming a cold spot of proliferation. The results further show that the inferior part of the otocyst has a high level of proliferation, whereas the superior part does not. Since the superior part of the otocyst demonstrates outward expansion that is comparable to the inferior part, it appears that regional outgrowth of the otic vesicle is not necessarily coupled to cell proliferation. This study provides a basis for exploring the regulation and function of cell proliferation and cell death during inner ear morphogenesis.

Animals↗

Ex-vivo resection techniques in tissue-preserving surgery for liver malignancies.

Some primary and secondary liver tumours are not absolutely irresectable, but cannot be resected using a conventional approach because of the limited warm ischaemia tolerance of the liver or poor accessibility of the tumour region. In such situations, the techniques of ex vivo liver surgery, pioneered by Rudolf Pichlmayr some 10 years ago, offer new chances for R0 resection. All the three different approaches, namely "in situ"-, "ante situm"-, and "ex situ" resection, require the use of measures originally developed for transplantation, such as hypothermic liver perfusion and veno-venous bypass. They differ mainly in the extent to which major vessels are divided in order to achieve optimal mobility of the organ. The results show that radical resection can be achieved accomplished in many cases. If necessary, complex vascular reconstructions can be performed. Although perioperative morbidity and mortality are high, there are a number of long-term survivors. Tumour recurrence, however, remains the main problem over the long term. In conclusion, ex vivo liver surgery is an important extension of surgical treatment possibilities. However, the procedure is suitable only for a small number of carefully selected patients and should be reserved for use in specialised centres. Furthermore, in view of the fact that the results are not yet optimal, additive and adjuvant treatment modalities are needed.

Blood Loss, Surgical↗

Proximal versus distal gastric carcinoma--what are the differences?

BACKGROUND: The incidence of proximal gastric third carcinoma (PGC) has been rising in recent years. Classification and surgical therapy remain controversial. METHODS: Between May 1986 and October 1997, 532 patients were operated for primary gastric carcinoma. All patient data were analyzed retrospectively comparing findings in patients with PGC and those with distal gastric carcinoma (DGC). RESULTS: Two hundred fifty patients had a PGC, and 282 patients had a DGC. The rate of RO resections was 79.3% for PGC and 81.6% for DGC. In 93.9% of the patients with PGC total gastrectomy was performed; for DGC total gastrectomy was done in 74.5% of patients. Postoperative morbidity and mortality were 29.2% for PGC and 23.8% for DGC, and 3.2% for PGC and 3.5% for DGC, respectively. Patients with advanced tumor stages (stage III and IV) were more common in the PGC group (73.3% vs. 53.6% in DGC). After RO resection, the 5-year survival rate was 33.2% for PGC and 59.7% for DGC. CONCLUSIONS: There was no significant difference between the rates of RO resections for PGC and DGC. Total gastrectomy can be performed with low postoperative morbidity and mortality. PGC and DGC represent the same tumor entity, and prognosis is similar, but due to more advanced tumor stages, the long-term survival is worse for patients with PGC than for those with DGC. Left retroperitoneal lymphadenectomy may be indicated for PGC.

Adenocarcinoma↗

Thermodynamically distinct high and low affinity states of the A(1) adenosine receptor induced by G protein coupling and guanine nucleotide ligation states of G proteins.

The influence of the receptor-G protein coupling state and the guanine nucleotide ligation state of the G protein on the binding mechanism of A(1) adenosine receptor ligands has been investigated in [(3)H]-1,3-dipropyl-8-cyclopentylxanthine ([(3)H]-DPCPX) binding studies in rat brain membranes. Thermodynamic parameters of binding of A(1) adenosine receptor ligands of different intrinsic activities were determined in the absence or presence of GDP and compared to the binding mechanism after receptor-G protein uncoupling. In agreement with previous studies, it was found that xanthine and non-xanthine antagonists showed an enthalpy- or enthalpy- and entropy-driven binding mechanism under all conditions. In contrast to antagonists, the binding mechanism of agonists was strongly affected by the G protein coupling state or the absence or presence of guanine nucleotides. Binding of full and partial agonists to the high-affinity state of the A(1) receptor was entropy-driven in the absence of GDP, and a good correlation between intrinsic activities and the contribution of entropy was observed. In the absence of GDP, binding of full and partial agonists and antagonists to the high affinity state of the receptor was thermodynamically discriminated. In contrast, no such discrimination was found in the presence of GDP. The binding mechanism of agonists to the low-affinity state of the receptor was identical to that of antagonists only after uncoupling of the receptor from G proteins by pretreatment with N-ethylmaleimide or guanosine-5'-(gamma-thio)-triphosphate (GTPgammaS). These results indicate the existence of two thermodynamically distinct high- and low-affinity states of the A(1) adenosine receptor.

Animals↗

Allogeneic bone marrow transplantation from unrelated donors using in vivo anti-T-cell globulin.

Despite improvements in HLA typing, graft-versus-host disease (GVHD) continues to impair the results after volunteer unrelated donor bone marrow transplantation (VUD-BMT) in adult patients compared with matched sibling BMT. Here, the outcome after VUD-BMT using a specific regimen with high-dose anti-T-lymphocyte globulin (ATG) was analysed. Fifty-five adult patients, median age 34 years (range 17-55 years), with acute or chronic leukaemia or myelodysplastic syndrome (MDS) were transplanted in first complete remission (CR1)/first chronic phase (CP1) (early disease) (n = 21) or in advanced (CR2/CP2, no remission) disease (n = 34) from an unrelated marrow donor. GVHD prophylaxis consisted of ATG-S (Fresenius) 60-90 mg/kg b.w. prior to transplantation, in addition to cyclosporin A and short-course methotrexate. Graft failure did not occur and white blood cell count (WBC) > 1.0 x 10(9)/l was reached at median day +16. The cumulative incidence of acute (a)GVHD grade II-IV was 15% [95% CI (8%, 28%)] and of chronic GVHD was 51% [95% CI (38%, 68%)]. The cumulative incidence of relapse within 1 year was 0% [95% CI (0%, 19%)] and 21% [95% CI (11%, 40%)] for patients with early and advanced disease respectively. With a median follow-up of 28 months (range 16-45 months), 2-year disease-free and overall survival for patients transplanted in CR1/CP1 was 81% and 81% [95% CI (64%, 98%)], respectively, and for patients with advanced disease was 33% [95% CI (17%, 50%)] and 40% [95% CI (23%, 57%)] respectively. Complete and persistent donor chimaerism was seen in 77.5% of 40 patients evaluated. All 14 chronic myeloid leukaemia (CML)-CP1 patients became bcr-abl negative within 250 d. High-dose ATG pretransplant results in a low incidence of severe aGVHD without compromising donor chimaerism or elimination of minimal residual disease. Our results are similar to data obtained after matched sibling donor transplantation.

Acute Disease↗

Retrospective analysis of prognostic factors after liver resection and transplantation for cholangiocellular carcinoma.

BACKGROUND: Cholangiocellular carcinoma is an uncommon primary liver cancer, which may be mixed with hepatocellular carcinoma. A retrospective analysis was undertaken to evaluate the results of surgical treatment and to identify prognostic factors. METHODS: Between 1978 and 1996, 162 patients underwent surgery for cholangiocellular carcinoma: liver resection (n = 95), liver transplantation (n = 24) and exploratory laparotomy with and without drainage (n = 43). Univariate and multivariate analyses of prognostic factors were performed. RESULTS: Overall survival was 47 per cent at 1 year, 28 per cent at 2 years and 13 per cent at 5 years. Survival rates for patients with resectable tumours were 64, 43 and 21 per cent respectively, and for those who underwent liver transplantation 21, 8 per cent and zero respectively. Univariate analysis showed that the following variables had an effect on survival: age, jaundice, liver resection, T, N and M stage in the tumour node metastasis classification, Union Internacional Contra la Cancrum (UICC) tumour stage, tumour-free margins, vascular infiltration, tumour number, tumour size and serum level of carcinoembryonic antigen. Multivariate analysis identified jaundice, N and M category, and UICC tumour stage as independent prognostic factors. CONCLUSION: The data underscore the importance and prognostic value of the UICC tumour classification for cholangiocellular carcinoma. The prognosis of mixed tumours is no different. Liver resection remains the treatment of choice; transplantation offers no solution for otherwise unresectable tumours.

Aged↗