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C Langer

Publications and source records attributed to C Langer.

At least 73 records · Page 4Linked to original sources
PubMed2001

Cell-derived apolipoprotein E (ApoE) particles inhibit vascular cell adhesion molecule-1 (VCAM-1) expression in human endothelial cells.

Sub-endothelial infiltration of monocytes occurs early in atherogenesis and is facilitated by cell adhesion molecules that are up-regulated on activated endothelium. Apolipoprotein E (apoE) helps protect against atherosclerosis, in part, because apoE particles secreted by macrophages have local beneficial effects at lesion sites. Here, we hypothesize that such protection includes anti-inflammatory actions and investigate whether cell-derived apoE can inhibit tumor necrosis factor-alpha-mediated up-regulation of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). Two models were used to mimic endothelial exposure to macrophage-derived apoE. In the first, HUVECs were transiently transfected to secrete apoE; VCAM-1 induction inversely correlated with secretion of apoE into the media (r = -0.76, p < 0.001). In the second, incubation of HUVECs with media from recombinant Chinese hamster ovary (CHO) cells expressing apoE (CHO(apoE)) also reduced VCAM-1 in a dose-dependent manner (r = -0.70, p < 0.001). Characterization of CHO(apoE) cell-derived apoE revealed several similarities to apoE particles secreted by human blood monocyte-derived macrophages. The suppression of endothelial activation by apoE most likely occurs via stimulation of endothelial nitric oxide synthase; apoE increased levels of intracellular nitric oxide and its surrogate marker, cyclic guanosine monophosphate, while the nitric oxide synthase inhibitor, ethyl-isothiourea, blocked its effect. We propose that apoE secreted locally at lesion sites by macrophages may be anti-inflammatory by stimulating endothelium to release NO and suppress VCAM-1 expression.

Animals↗
PubMed2001

UltraCision or high-frequency knife in transanal endoscopic microsurgery (TEM)? Advantages of a new procedure.

The potential advantages of ultrasound dissection using UltraCision (UC) an ultrasonically activated scalpel, rather than conventional electrosurgery (ES) were investigated retrospectively in 63 patients following transanal endoscopic microsurgery (TEM) in 22 cases of rectal carcinoma (16 pT1, four pT2, two pT3), 40 cases of rectal adenoma >2 cm, and one neurinoma. In all, 21 patients (13 adenomas, seven carcinomas, and one neurinoma) were operated with UltraCision (Ethicon, Norderstedt, Germany), whereas 42 patients (27 adenomas, 15 carcinomas) were treated with conventional electrocautery. All tumors were completely excised (R0) in both groups. We encountered a total of nine complications, seven after ES and two after UC use. Surgical reintervention was necessary in three cases (4.7%), exclusively following resection by ES. There were five cases of tumor recurrence (7.9%), once again only in the ES group. The advantages of ultrasound dissection are magnified under the particular conditions of minimally invasive endoscopic rectum surgery by means of TEM. In principle, all the known risks associated with the application of electric current can be avoided by using ultrasound technology.

Adenoma↗
PubMed2001

[Endosonography in epithelial rectal tumors. Value of a differentiated therapy concept].

INTRODUCTION: Endorectal ultrasound (EU) is the most important examination for pretherapeutic stratification of primary rectal tumors. Preoperative histology and endosonography determine the therapeutic strategy by using the criteria of depth of infiltration (uT) and lymph node status (uN). METHODS: The effectiveness of endoluminal ultrasound in the preoperative differentiation between locally restricted tumors (adenomas and "low-risk" carcinomas, uT0/1, G1-2) and advanced rectal carcinomas (uT3) was assessed in a retrospective study of 284 patients. In the examination period (UZ) from 3/94 to 12/97 (UZ I) 104 patients (group 1) were examined with a 7-MHz endoprobe, and from 1/98 to 12/99 (UZ II), 116 (group 2) with a 10-MHz endoprobe. Additionally, in 64 patients (group 3) with an advanced uT3/4 or uN + tumor we compared the accuracy of ultrasound with computed tomography (CT). In this group 32 patients were restaged by EU and CT after preoperative chemoradiation. The results of präoperative endorectal ultrasound were correlated with the postoperative histological data. RESULTS: Concerning the whole period (UZ I and II) we achieved a total hit rate of 83.6% for adenomas and "low-risk" carcinomas (uT0/1, G1/2) by EU (79.8% in UZ I, 87.1% in UZ II). For advanced rectal carcinoma (> or = uT3) we found a total accuracy of 87.3% (82.7% in UZ I, 91.4% in UZ II). In 62 cases endosonographic lymph node status was correlated with postoperative histology during UZ II, with a hit rate of 64.5%. In group 3 (n = 64), in 32 patients without preoperative chemoradiation we found an accuracy for depth infiltration of 93% (EU) and 82% (CT). Concerning lymph node status there was a correlation of 57% (EU) and 64% (CT). After preoperative chemoradiation (n = 32) we found an accuracy of 91% (EU) and 73% (CT) for depth infiltration--for lymph node status 70% (EU) and 82% (CT). CONCLUSIONS: High accuracy in endoluminal ultrasound leads to a secure and differentiated stratification of therapy in primary rectal tumors. The hit rate concerning depth of infiltration is higher for EU than for CT both before and after chemoradiation, but not regarding lymph node status.

Adenoma↗
PubMed2001

[Problem of recurrent incisional hernia after mesh repair of the abdominal wall].

INTRODUCTION: Depending on the surgical technique, mesh material and follow-up, the figures for recurrences of incisional hernia vary from 0 to 31%. What are the reasons for recurrences, and which options exist for more successful therapy? METHODS: Fourteen operations for recurrences after mesh repair of incisional hernias were analyzed retrospectively and correlated with a literature review of the years 1990-2000. RESULTS: An inadequate surgical technique is the main reason for recurrences after the use of polypropylene or polyester, but with PTFE, it is instead the properties of the material. In our patients we found central mesh recurrences. The first results with laparoscopic technique are very promising. CONCLUSIONS: Open incisional hernia mesh repair should be performed with the sublay technique, preferably with polypropylene; the use of polyester can be recommended only with reservations and the use of PTFE ought to be limited to very few indications. The entire incision should always be prepared with safe fixation of the mesh and wide overlap of the hernia. Recurrences after polypropylene implantation can be treated with additional mesh; concerning PTFE, a different material is recommended. A final evaluation of laparoscopic mesh repair cannot be assessed yet.

Adult↗
PubMed2001

[Standardized sublay technique in polypropylene mesh repair of incisional hernia. A prospective clinical study].

INTRODUCTION: With the introduction of meshes to support hernia repairs the recurrence rates were reduced from 50% to less than 10%. Special complications such as scar plates with restriction of the mobility of the abdominal wall, pain and fistula formation are described. METHODS: In a prospective study trial 38 patients with incisional hernia were treated with Marlex mesh repair in the standard sublay technique. RESULTS: Within a mean follow-up period of 3 years most of the patients were free from pain and very satisfied. Two recurrences (5.2%) occurred and 2 hematomas (5.2%) had to be removed surgically. CONCLUSIONS: Using a standard operation technique with the mesh in sublay position, even with heavy-weight Marlex mesh, good clinical results can be achieved compared to published findings. To our surprise we found two central recurrences through the mesh.

Adult↗
PubMed2001

Central mesh recurrence after incisional hernia repair with Marlex--are the meshes strong enough?

The use of biomaterial meshes in the repair of incisional abdominal wall hernias is now widely accepted internationally. The introduction of synthetic meshes to achieve tension-free repair has led to a satisfactory reduction in the recurrence rate to less than 10%. However, the use of such biomaterials can result in the occurrence of undesirable complications such as increased risk of infection, seromas, restriction of the abdominal wall and failure caused by mesh shrinkage. Additionally, at the time of writing there is much discussion concerning the potential risk of a persistent foreign body reaction directly associated with the meshes with regard to possible malignant transformation. As such, the trend seems to be toward the use of lighter meshes utilizing less non-absorbable material. One particular novel mesh theoretically capable of guaranteeing the necessary mechanical stability uses 70% less biomaterial. Against this background, we report a central mesh recurrence through the mesh following incisional hernia repair with a Marlex mesh. To our knowledge, this is the first description of a central mesh recurrence, and we discuss a possible mechanism with particular emphasis on the required abdominal wall forces both physiologically and after incisional hernia repair.

Elasticity↗
PubMed2001

[Ultrasound diagnosis of Meckel diverticulitis in adults].

Meckel's diverticulitis is a rare disease. In addition to physical examination, abdominal ultrasound can help to pinpoint the diagnosis. By presenting a case report we would like to demonstrate the typical ultrasonographic findings in acute Meckel's diverticulitis and differentiate it from acute appendicitis. A 60-year-old patient was admitted to our hospital with the diagnosis of acute appendicitis. Abdominal ultrasound was performed and a blind ending, liquid-filled segment of small bowel in the right lower quadrant of the abdomen found. This segment was not compressible, no peristalsis was evident, nor was there any anatomical association with the cecum. Locally we found free fluid and hints of inflamed mesenteric fatty tissue. A perforated Meckel's diverticulum was diagnosed and confirmed intraoperatively. The major ultrasonographic difference between an inflamed Meckel's diverticulum and acute appendicitis is its anatomical location. In contrast to the appendix there is no association with the cecum. A diameter of up to 40 mm and a well-defined wall of small bowel with 3 definite layers visible by ultrasound may help to distinguish between a Meckel's diverticulum and the appendix.

Acute Disease↗
PubMed2001

Atherosclerosis in apolipoprotein E-deficient mice is decreased by the suppression of endogenous sex hormones.

To elucidate the influence of gonadotropins, endogenous sex hormones and testosterone on atherosclerosis, 4-week-old male and female apoE-deficient mice received either 100 microg subcutaneous injections of the gonadotropin-releasing hormone (GnRH) antagonist Cetrorelix every 48 hours or a subcutaneous implantation of a permeable silastic tube with 35 mg of testosterone. Control mice received either subcutaneous injections of saline, a silastic implant with saline, or no treatment. The animals were sacrificed after eight weeks of treatment; blood was obtained by cardiac puncture and the aorta was taken out and prepared. The suppression of testosterone led to an increase in atherosclerosis in both the sinus aortae and the ascending aorta despite increases of cholesterol in male and decreases of HDL cholesterol in female mice. Treatment with testosterone led to small but significant increases of cholesterol levels and atherosclerotic lesions in male mice. Female mice showed no change in lipids and fewer atherosclerotic lesions. In conclusion, the suppression of gonadotropins appears to have a moderate anti-atherogenic effect. The effect of testosterone appears to be either neutral or opposed by gonadotropins.

Animals↗
PubMed2001

ATP binding cassette transporter ABCA1 modulates the secretion of apolipoprotein E from human monocyte-derived macrophages.

Apolipoprotein E (apoE) produced by macrophages in the arterial wall protects against atherosclerosis, but the regulation of its secretion by these cells is poorly understood. Here we investigated the contribution of the adenosine triphosphate binding cassette transporters ABCA1 and ABC8 to the secretion of apoE from either primary human monocyte-derived macrophages (HMDM) or human THP1 macrophages. During incubations of up to 6 h, apoE secretion from both THP1 macrophages and HMDM was stimulated by 8-Br-cAMP, which activates ABCA1 expression. The putative ABCA1 inhibitor glyburide and antisense oligonucleotides directed against ABCA1 mRNA significantly reduced apoE secretion from THP1 macrophages and HMDM. Antisense oligonucleotides directed against ABC8 mRNA also inhibited apoE secretion, although this inhibition was less pronounced and consistent than in the case of ABCA1. ApoE secretion from HMDM of ABCA1-deficient patients with Tangier disease was also decreased. ApoE mRNA expression was not affected by inhibition of ABCA1 or ABC8 in normal HMDM or the lack of functional ABCA1 in HMDM from Tangier disease patients. Inhibition of ABCA1 in HMDM prevented the occurrence of anti-apoE-immunoreactive granular structures in the plasma membrane. We conclude that ABCA1 and, to a lesser extent, ABC8 both promote secretion of apoE from human macrophages.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed2001

Lack of efficacy of topotecan in the treatment of metastatic or recurrent squamous carcinoma of the head and neck: an Eastern Cooperative Oncology Group Trial (E3393).

Recurrent or metastatic squamous carcinoma of the head and neck (RMSCHN) is a modestly chemoresponsive tumor; however, currently available agents have failed to improve survival. New active agents are needed for the treatment of this disease. Topotecan is a topoisomerase inhibitor that demonstrated initial promising activity in squamous carcinoma of the head and neck. The Eastern Cooperative Oncology Group conducted a phase II trial of topotecan to determine the efficacy and toxicity of a weekly treatment schedule in patients with RMSCHN. Patients with metastatic or locally recurrent squamous carcinoma of the head and neck were treated with topotecan 1.5 mg/m2 x 24 hours by continuous infusion on days 1, 8, 15, and 22 of each 35-day cycle. Patients were stratified in two cohorts: chemonaive and previously treated. Sixteen chemonaive and 16 previously treated patients were registered on study. Grade III/IV neutropenia and anemia occurred in 16% and 18% of patients, respectively. No responses were observed in either cohort. Median survival for previously untreated patients was 4.6 months and 3.2 months for previously treated patients. Topotecan failed to demonstrate efficacy in patients with RMSCHN. Further evaluation of this agent is not planned.

Adult↗
PubMed2000

Phase II, two-arm RTOG trial (94-11) of bischloroethyl-nitrosourea plus accelerated hyperfractionated radiotherapy (64.0 or 70.4 Gy) based on tumor volume (> 20 or < or = 20 cm(2), respectively) in the treatment of newly-diagnosed radiosurgery-ineligible glioblastoma multiforme patients.

PURPOSE: To compare survivorship, and acute and delayed toxicities following radiation therapy (RT) of radiosurgery-ineligible glioblastoma multiforme (GBM) patients treated with tumor volume-influenced, high-dose accelerated, hyperfractionated RT plus bischloroethyl-nitrosourea (BCNU), using prior RTOG malignant glioblastoma patients as historical controls. METHODS AND MATERIALS: One hundred four of 108 patients accrued from June 1994 through May 1995 from 26 institutions were analyzable. Patients were histologically confirmed with GBM, and previously untreated. Treatment assignment (52 patients/arm) was based on tumor mass (TM), defined as the product of the maximum diameter and greatest perpendicular dimension of the titanium-gadolinium-enhanced postoperative MRI: Arm A, 64 Gy, TM > 20 cm(2); or Arm B, 70.4 Gy, TM < or = 20 cm(2). Both Arms A and B received BCNU (80 mg/m(2), under hyperhydration) days 1-3, 56-58, then 4 cycles, each 8 weeks, for a total of 6 treatment series. RESULTS: During the 24 months immediately post-treatment, the overall median survival was 9.1 months in Arm A (64 Gy) and 11.0 months in Arm B (70.4 Gy). Median survival in recursive partitioning analysis (RPA) Class III/IV was 10.4 months in Arm A and 12.2 months in Arm B, while RPA Class V/VI was 7.6 months in Arm A and 6.1 months in Arm B. There were no grade 4 neurological toxicities in Arm A; 2 grade 4 neurological toxicities were observed in Arm B (1 motor deficit, 1 necrosis at 157 days post-treatment). CONCLUSION: This strategy of high-dose, accelerated hyperfractionated radiotherapy shortens overall RT treatment times while allowing dose escalation, and it provides the potential for combination with currently available, as well as newer, chemotherapy agents. Survival is comparable with previously published RTOG data, and toxicities are within acceptable limits.

Antineoplastic Agents, Alkylating↗
PubMed2000

Experimental entanglement of four particles

Quantum mechanics allows for many-particle wavefunctions that cannot be factorized into a product of single-particle wavefunctions, even when the constituent particles are entirely distinct. Such 'entangled' states explicitly demonstrate the non-local character of quantum theory, having potential applications in high-precision spectroscopy, quantum communication, cryptography and computation. In general, the more particles that can be entangled, the more clearly nonclassical effects are exhibited--and the more useful the states are for quantum applications. Here we implement a recently proposed entanglement technique to generate entangled states of two and four trapped ions. Coupling between the ions is provided through their collective motional degrees of freedom, but actual motional excitation is minimized. Entanglement is achieved using a single laser pulse, and the method can in principle be applied to any number of ions.

Journal Article↗
PubMed2000

Endogenous apolipoprotein E modulates cholesterol efflux and cholesteryl ester hydrolysis mediated by high-density lipoprotein-3 and lipid-free apolipoproteins in mouse peritoneal macrophages.

We investigated the effect of endogenous apolipoprotein (apo) E synthesis in mouse peritoneal macrophages on cholesterol efflux and intracellular cholesteryl ester hydrolysis mediated by high-density lipoprotein-3 (HDL3) and lipid-free apolipoproteins (apo). After loading with acetylated LDL (acLDL) peritoneal macrophages from wild-type (apoE(+/+)) and apoE-deficient (apoE(-/-)) mice were incubated with medium alone or with liposomes, HDL3, lipid-free apoA-I, or lipid-free apoE3. Cholesterol and cholesteryl esters in the cells and culture media were quantified by HPLC. Incubation of apoE(+/+) or apoE(-/-) macrophages for 18 h with medium alone or with liposomes did not cause significant changes in cellular cholesterol. Addition of HDL3, apoA-I, or apoE3 to the medium led to significant cholesterol efflux, which was less efficient in apoE(-/-) macrophages than in apoE(+/+) macrophages. HDL and lipid-free apolipoproteins were more effective in reducing the cellular content of cholesteryl esters of apoE(+/+) macrophages than of apoE(-/-) macrophages, suggesting that endogenous apoE stimulates cholesteryl ester hydrolysis. The difference in the mass of cholesteryl esters was more pronounced for cholesteryl arachidonate and linoleate than for cholesteryl oleate or palmitate. Furthermore, in [(14)C]arachidonate labeling experiments cholesterol arachidonate hydrolysis was higher in apoE(+/+) macrophages than in apoE(-/-) macrophages in the presence of cholesterol efflux mediated by HDL3 or apoA-I. In contrast, in the absence of cholesterol efflux cholesterol arachidonate synthesis was higher in apoE(+/+) macrophages than in apoE-/- macrophages. Taken together, our data suggest that endogenous apoE stimulates cholesterol efflux and intracellular cholesteryl ester hydrolysis mediated by HDL3 and lipid-free apolipoproteins in mouse peritoneal macrophages. This may contribute to the antiatherogenic effect of apoE.

Animals↗