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Biomedical subjects

B Lehner

Publications and source records attributed to B Lehner.

At least 19 recordsLinked to original sources

[The influence of jet-lavage systems on in vitro cement penetration].

The benefit of pulsatile lavage on cement penetration in femoral cancellous bone is well known. The aim of this study was to determine the influence of different jet-lavage systems on cement penetration in a standardized cadaver study. Four different jet-lavage systems were compared (right vs left) in 30 paired human femora. After broaching, the femoral canal was lavaged with 1 l saline. The specimens were embedded in plastic pots, bone cement was applied in a retrograde manner and cement was pressurized using a standard pressure protocol with a constant force of 3,000 N. Horizontal sections were obtained at predefined levels using an automatic saw. Microradiographs were taken and analysed using image analysis to assess the extent of cement penetration. There were no significant differences in cement penetration into cancellous bone using the different jet-lavage systems. This technique is of great importance for obtaining a good interdigitation with cancellous bone. The different jet-lavage systems investigated in our study, however, seemed to be equally effective.

Absorption↗

[V.A.C.-instill therapy in periprosthetic infection of hip and knee arthroplasty].

Periprosthetic infection represents a main complication of arthroplasty. In case of an early infection the implant often can be left in place. Whether instillation of antiseptic solution using a reticulated sponge in combination with negative pressure wound therapy (V.A.C.-Instill) can be useful was the aim of our investigation. Up to now the instillation of Lavasept in combination with negative pressure wound therapy could be performed in three patients. In two cases an early infection of a hip prosthesis and one infected knee implant had to be treated. Following surgical debridement V.A.C.-Instill therapy was performed for 4-7 days followed by closure of the wound or a repeated application. Lavasept was used for irrigation. In all three cases retention of the primary implant could be achieved. The follow up now is 8 to 22 weeks. No recurrence of the infection occurred. After salvage of the prosthesis the joint allowed full load bearing and painfree mobilisation. The V.A.C.-Instill system proved to be easy to use. With this system early periprosthetic infection with antiseptic irrigation in combination with negative pressure wound therapy decreasing the bacterial burden, salvage of prosthesis seems to be possible. The therapy is applicable in hip and knee prosthesis. Final conclusions about this therapy however can be done only after a larger series of patients.

Aged↗

[Effect of femoral cementing technique on results. Comparison between retrograde technique and vacuum application].

METHODS: To evaluate the penetration depth of cement into trabecular femoral bone, femora of 14 sheep were subjected to simultaneous bilateral cementing. After femoral neck osteotomy, preparation of the bone cavities and jet lavage, cement was applied simultaneously using the conventional retrograde method for one side and vacuum application for the contralateral limb. Bilateral simultaneous pressurisation was then applied. All femoral specimens were X-rayed, sawed into standardised, horizontal, stereometric, identical slices and microradiographed. Cement penetration was assessed using a morphometric software system. RESULTS: No significant differences in depth of cement penetration between sheep femora cemented with the vacuum application method and the standard retrograde method could be found or between the ratio of cement-consolidated and non-cement-consolidated cancellous bone. CONCLUSION: The more complicated and technically challenging method of cement application under vacuum had no advantage in terms of cement interdigitation over the standard retrograde method.

Animals↗

Radiation-induced impairment of osseous healing with vascularized bone transfer: experimental model using a pedicled tibia flap in rat.

Aim of this study was to establish an appropriate animal model for investigating the healing of vascularized osseous transplants to irradiated recipient sites applying metabolic, vascular and immunologic experimental studies. In 20 Wistar rats (male, weight 300-500 g), a pedicled osseous tibia flap was raised and transferred to a subcutaneous pocket in the ipsilateral groin. The remaining tibia was stabilized with a monocortical titanium miniplate. To create a pre-irradiated transplant bed, the donor-area including the adjacent bone of the tibia was irradiated with a total dose of 50Gy (5 x 10 Gy) in 10 animals. The interval between irradiation and retransfer of the non-irradiated pedicled tibia flap was 4 weeks. Ten animals received no radiation. Evaluation of osseous healing and the success of the transferred flap were based on a clinical and quantitative histomorphometric assessment. Testing for significant differences was performed using the non-parametric Mann-Whitney U-test. The rate of complete osseous healing in the non-irradiated animals was 90%. In contrast there was no significant bone union observed in the group of the pedicled flaps grafted to the pre-irradiated (50Gy) recipient site (P = 0.001). Similarly bone formation in the transitional zone between bone graft and recipient bone was significantly lower in the preirradiated group (P < 0.001) (16.9 +/- 3%) in contrast to the non-irradiated transplant bed (47.9 +/- 6%).

Animals↗

[Etiology of rotator-cuff-tears and consequences for legal assessment].

Traumatic or degenerative etiology of rotator-cuff-tears is a matter of controversial discussion in legal proceedings. This article presents a review on the literature about current knowledge of anatomy, biomechanics and pathogenesis of rotator-cuff pathology. According to this a catalogue of potentially adequate and inadequate trauma mechanisms is proposed. Furthermore clinical history and examination as well as sonographic and radiologic findings and intraoperative pathology may help to distinguish between traumatic and degenerative changes of rotator-cuff lesions. The keypoints for and against traumatic etiology of rotator-cuff-tears are mentioned that could help the expert in the preparation of an adequate expert opinion.

Diagnosis, Differential↗

[Post-traumatic loss of function and malunion of the elbow].

Post-traumatic contracture and malunion of the elbow in pediatric patients may result from a combination of injury-related, diagnostic-related and therapy-related factors. Typical pediatric elbow injuries are associated with different patterns of these risk factors. Etiological differentiation allows for initial risk prediction, improves diagnostic awareness and provides adequate treatment in order to prevent unsatisfactory results.

Child↗

Quantitative evaluation of skeletal tumours with dynamic FDG PET: SUV in comparison to Patlak analysis.

This study was carried out to evaluate bone lesions using fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) and to explore whether dynamic and quantitative PET data may help to differentiate benign lesions from malignant masses. Forty patients with primary bone lesions were studied. The final diagnosis was confirmed by histopathology. A 60-min dynamic FDG PET acquisition was undertaken in all subjects. From the dynamic PET images, indices such as the average and maximal standardised uptake values (SUVs), the tumour SUV-to-muscle SUV ratio (T/M) and the SUV at 60 min-to-SUV at 30 min ratio (averSUV60/30 min and maxSUV60/30 min) were produced. Patlak graphical analysis was used to obtain the influx constant (Ki), and the metabolic rate of FDG (MRFDG) was calculated. Based on the receiver operator characteristic curve, the sensitivity and specificity for each parameter in differentiating between malignant and benign lesions were evaluated. The histological results revealed 21 malignant tumours and 19 benign lesions in this group. The MRFDG and SUV indices in malignant lesions were significantly higher than those in benign lesions. However, each index showed a considerable overlap between benign and malignant lesions. Average SUV correlated positively with MRFDG (r=0.67). When a cut-off of 1.8 average SUV was used, the sensitivity and specificity for discrimination of malignancy from benign disease were 85% and 82.4%, respectively. MRFDG showed a similar sensitivity (82.4%) and a better specificity (92.9%). A combination consisting of a cut-off of average SUV (1.8) and averSUV60/30 min (1.1) resulted in an improvement of specificity to 93.3%, with a small reduction in sensitivity (81.3%) as compared with exclusive use of SUV. The results of this study indicate that a detectable difference in glucose metabolism exists between malignant and benign skeletal lesions. The static FDG uptake indices alone may not enable adequate differentiation between benign and malignant lesions. Quantitative dynamic imaging may provide more helpful information, but will not permit a definite diagnosis. The use of uptake indices may represent an alternative and interesting approach to the evaluation of bone lesions.

Adolescent↗

Cement penetration in the proximal femur does not depend on broach surface finish.

In a cadaver study, we prepared 29 paired human cadaver femora using 3 different broaches of identical geometry but different surface characteristics. In one group of 20 pairs, preparation with chipped-toothed broaches was compared to diamond-shaped broaches; in the other group of 9 pairs, polished tamps for compaction of cancellous bone were compared with chipped-tooth broaches. Cancellous bone was irrigated with 1 liter pulsed lavage. The specimens were embedded in specially-designed pots. Palacos R and Simplex bone cements were used. After vacuum mixing, the cement was applied in a retrograde manner and subjected to a standard pressure protocol with a constant force of 3,000 N. Radiographs were taken and horizontal sections were obtained at predefined levels using a diamond saw. Microradiographs were taken, digitized and analyzed to assess cement penetration into cancellous bone. In 6 of 9 femora prepared using smooth tamps, femoral fractures occurred despite careful preparation technique. The microradiographic evaluation showed no significant morphometric differences between diamond and chipped-tooth or between polished and chipped-tooth broaches with regard to cement penetration into cancellous bone. Therefore, in the presence of pulsed lavage, one finds no significant effect of broach surface characteristics on cement penetration into cancellous bone of the proximal end of the femur.

Absorption↗

Purification, characterization, DNA sequence and cloning of a pimeloyl-CoA synthetase from Pseudomonas mendocina 35.

A pimeloyl-CoA synthetase from Pseudomonas mendocina 35 was purified and characterized, the DNA sequence determined, and the gene cloned into Escherichia coli to yield an active enzyme. The purified enzyme had a pH optimum of approximately 8.0, Km values of 0.49 mM for pimelic acid, 0.18 mM for CoA and 0.72 mM for ATP, a subunit Mr of approximately 80000 as determined by SDS/PAGE, and was found to be a tetramer by gel-filtration chromatography. The specific activity of the purified enzyme was 77.3 units/mg of protein. The enzyme was not absolutely specific for pimelic acid. The relative activity for adipic acid (C6) was 72% and for azaleic acid (C9) was 18% of that for pimelic acid (C7). The N-terminal amino acid was blocked to amino acid sequencing, but controlled proteolysis resulted in three peptide fragments for which amino acid sequences were obtained. An oligonucleotide gene probe corresponding to one of the amino acid sequences was synthesized and used to isolate the gene (pauA, pimelic acid-utilizing A) coding for pimeloyl-CoA synthetase. The pauA gene, which codes for a protein with a theoretical Mr of 74643, was then sequenced. The deduced amino acid sequence of the enzyme showed similarity to hypothetical proteins from Archaeoglobus fulgidus, Methanococcus jannaschii, Pyrococcus horikoshii, E. coli and Streptomyces coelicolor, and some limited similarity to microbial succinyl-CoA synthetases. The similarity with the protein from A. fulgidus was especially strong, thus indicating a function for this unidentified protein. The pauA gene was cloned into E. coli, where it was expressed and resulted in an active enzyme.

Acyl Coenzyme A↗

Biotin production under limiting growth conditions by Agrobacterium/Rhizobium HK4 transformed with a modified Escherichia coli bio operon.

The E. coli biotin (bio) operon was modified to improve biotin production by host cells: (a) the divergently transcribed wild-type bio operon was re-organized into one transcriptional unit; (b) the wild-type bio promoter was replaced with a strong artificial (tac) promoter; (c) a potential stem loop structure between bioD and bioA was removed; and (d) the wild-type bioB ribosomal binding site (RBS) was replaced with an artificial RBS that resulted in improved bioB expression. The effects of the modifications on the bio operon were studied in E. coli by measuring biotin and dethiobiotin production, and bio gene expression with mini-cells and two-dimensional polyacrylamide gel electrophoresis. The modified E. coli bio operon was introduced into a broad host-range plasmid and used to transform Agrobacterium/Rhizobium HK4, which then produced 110 mg L-1 of biotin in a 2-L fermenter, growing on a defined medium with diaminononanoic acid as the starting material. Biotin production was not growth-phase dependent in this strain, and the rate of production remained high under limiting (maintenance) and zero growth conditions.

Journal Article↗

Perfusion of colorectal liver metastases and uptake of fluorouracil assessed by H2(15)O and [18F]uracil positron emission tomography (PET).

Perfusion and fluorouracil (FU) accumulation were assessed using positron emission tomography (PET) with H2(15)O and 18FU in 36 patients with colorectal liver metastases. The tracers were injected intravenously and via the hepatic artery. Standard uptake values (SUV) were calculated using a region of interest (ROI) technique. The perfusion of non-tumorous liver tissue was similar after intravenous (i.v.) and intra-arterial (i.a.) assessment [mean of 2.67 (s = 0.61) and 2.2 (s = 0.45)]. Metastases were found to be hypoperfused compared to normal liver tissue after i.v. examinations [mean 1.73 (s = 0.77)]; i.a. injections revealed greater perfusion in metastases [mean 6.41 (s = 5.47)]. Single metastases showed up to 10 times greater perfusion with the i.a. injection route than with the i.v. one. However, lesions with no change or lower perfusion were also observed. Generally, accumulation of 18FU in metastases after i.v. infusion was less than after i.a.. Correlation of i.v. perfusion and uptake was moderate (r = 0.54, P = 0.0001); i.a. correlation was only slightly better (r = 0.61, P = 0.008). Perfusion as measured by H2(15)O-PET does not generally predict uptake of 18FU in colorectal liver metastases. To measure FU uptake using PET and 18F seems to be the most accurate method. It would allow one to identify individual patients with considerably greater accumulation of 18FU following i.a. administration who should profit from a cross-over to intrahepatic chemotherapy.

Colorectal Neoplasms↗

In vitro and clinical characterisation of a Newcastle disease virus-modified autologous tumour cell vaccine for treatment of colorectal cancer patients.

A virus-modified autologous tumour cell vaccine prepared from human colorectal cancer cells is described. After dissociation an average of 5 x 10(7) cells/g tissue were obtained from primary tumours and 9 x 10(7)/g tissue from metastases with an average viability of 72% and 51%, respectively. Following irradiation (200 Gy), inactivation of the proliferative activity of the cells was demonstrated by their degeneration in tissue culture and the absence of incorporation of 3H-labelled thymidine. One third of the cells were still metabolically active, as shown by the incorporation of 3H-uridine and a mixture of 3H-aminoacids. The dissociated cells expressed MHC class I and II antigens in a qualitatively similar way to tissue sections. Epithelium-specific antigens (detected by MAb HEA125) were expressed on an average of more than 75% cells of the suspension, while leucocyte-specific antigens (detected by MAb CD53) were expressed on an average of less than 25% cells. The vaccine was prepared by admixing the nonlytic strain Ulster of Newcastle disease virus (NDV) with the tumour cell suspension. The NDV adsorption at tumour cells was shown by electron microscopy. Clinically, the treatment with the vaccine was associated with an increased sensibilisation against autologous tumour cells, measured by DTH skin reactivity. First results in 23 patients with colorectal liver metastases who underwent "curative" liver resection followed by vaccination show a clear correlation between the induced increase of DTH skin reaction against autologous tumour cells and the recurrence-free interval. No correlation was found for DTH reaction caused by standard antigens (Mérieux test), NDV alone or autologous normal liver tissue. The results demonstrate the possibility of preparing immunogenic virus-modified autologous tumour cell vaccine from colorectal cancer tissue, which could be used for cancer therapy.

Adult↗

Postoperative active specific immunization in curatively resected colorectal cancer patients with a virus-modified autologous tumor cell vaccine.

Active specific immunotherapy was performed in a phase I study in 20 colorectal cancer patients after surgical resection of the tumor. An autologous tumor cell vaccine surface modified by Newcastle disease virus (NDV) was used, which showed the following characteristics. After mechanical and enzymatic dissociation of the tumor tissue an average of 5 x 10(7) cells/g tissue was obtained. According to trypan blue dye exclusion assay the average viability was 72%. Following irradiation (200 Gy) the inactivation of proliferative activity of the cells could be demonstrated by the absence of incorporation of 3H-labelled thymidine. The cells were, however, still metabolically active as shown by the incorporation of [3H]-uridine and a mixture of 3H-labelled amino acids. Epithelium-specific antigens (detected by mAb HEA125) were expressed on more than 75% cells of the cell suspension indicating a high amount of (epithelium-derived) tumor cells. In order to increase the immunogenicity of the tumor cells the suspended cells were infected by the nonlytic, apathogenic Ulster strain of NDV. The successful modification of tumor cells with NDV could be shown by electron microscopy. Three weeks postoperatively cells were thawed, virus-modified, and inoculated intradermally in the upper thigh. Several cell and virus concentrations were tested in each patient. As control, tumor cells without NDV, NDV alone and normal colon mucosa were used. The number of tumor cells ranged from 2 x 10(6) up to 2 x 10(7) cells and NDV concentrations from 4 to 64 hemagglutination units (HU) were tested. Sixteen patients responded with a delayed-type hypersensitivity (DTH) skin reaction to the vaccine. The best DTH reaction, measured 24 h following vaccination, was obtained using a vaccine consisting of 1 x 10(7) tumor cells and 32 HU NDV (median induration of 8 mm). Response to NDV alone was seen in 2 patients only (median induration of 3 mm); 12 patients responded to tumor cells (1 x 10(7) alone (median induration of 4 mm). Of 10 patients tested with normal colorectal mucosa, 4 responded with a median induration of 3.5 mm. DTH responses to the vaccine of 1 x 10(7) tumor cells and 32 HU NDV increased throughout the repeated vaccinations to a median induration of 9.5 mm at the end of the therapy. No severe side-effects in the course of the immunotherapy, except for mild fever in 4/20 patients, were observed. The results of our phase I study show that this type of autologous colorectal tumor cell vaccine is ready for a large clinical trial to prove its efficacy.

Carcinoembryonic Antigen↗

[The value of positron emission tomography in the diagnosis of recurrent rectal cancer].

In 21 patients with clinically suspected recurrent rectal cancer showing a mass in the pelvic CT scan, Positron Emission Tomography (PET) was performed to measure metabolic rate of the mass. In 13 of the 21 patients an increased F-18-Fluorodeoxyglucose (FDG) uptake in the suspect tissue could be found. All of these patients were proven to suffer recurrent cancer by biopsy. 8 of the 21 patients showed normal uptake and 7 of them revealed scar tissue by histology. Therefore PET could distinguish clearly between cancer and scar tissue.

Deoxyglucose↗

Scar or recurrent rectal cancer. Positron emission tomography is more helpful for diagnosis than immunoscintigraphy.

We used positron emission tomography and fludeoxyglucose F 18 to assess metabolic activity of a pelvic mass in 18 patients who had suspected recurrent rectal cancer. Computed tomography could not differentiate tumor from scar. All patients presenting increased uptake of fludeoxyglucose F 18 by the mass were proved by histologic studies to suffer from recurrent tumor. Six of seven patients with low fludeoxyglucose uptake had nonmalignant lesions. Using immunoscintigraphy in 14 patients with elevated carcinoembryonic antigen levels, only four of ten recurrences could be identified by increased antibody accumulation in the mass. On the other hand, two of four benign lesions were interpreted as being recurrent tumor because of high uptake. Therefore, only positron emission tomography seems to be a useful diagnostic tool in the differentiation of recurrent rectal cancer and scar by providing information about the metabolic activity of a mass.

Antibodies, Monoclonal↗

Recurrence of colorectal tumors: PET evaluation.

Positron emission tomography (PET) was used in the follow-up of patients with colorectal malignancies to differentiate between recurrent colorectal tumor and scar. Patients were examined with oxygen-15-labeled water and with fluorine-18-labeled deoxyglucose (FDG). FDG was injected intravenously to assess tumor metabolism. The tracer concentration was quantitatively evaluated by means of a region-of-interest technique and standardized for both injected dose and body volume. Of 29 patients, 21 had recurrent colorectal malignancy, and eight had a nonmalignant mass. All malignancies were seen on the PET cross sections. Nonmalignant lesions had a low FDG accumulation on images obtained 60 minutes after injection. While the tumor-soft tissue ratio was highest shortly after the intravenous injection of FDG, the tumor-scar ratio was highest 60 minutes after injection. It was possible to differentiate tumor from non-malignant tissue with FDG with the use of standardized concentration values and tumor-soft tissue ratios. Imaging with O-15-labeled water gave no additional information.

Adult↗

Results of liver angiography and perfusion scintigraphy do not correlate with response to hepatic artery infusion chemotherapy.

Liver angiography and liver perfusion scintigraphy with Tc-99m-labeled macroaggregated albumin (MAA) were performed in 36 patients with liver metastases from colorectal cancer prior to continuous 5-fluorouracil hepatic artery infusion (HAI) hemotherapy. Of the 26 patients showing metastases on arteriogram, five revealed increased tumor vascularisation, five had normal vascularisation, and 16 showed decreased vascularisation of the metastases relative to liver. In liver perfusion scintigraphy, 15 of the 36 patients showed increased perfusion of the metastases, four had normal perfusion, and 17 had decreased tumor perfusion. The observed differences in survival in the different groups were not statistically significant: patients survived 15 months in the group with increased tumor vascularisation, 8 months for normal vascularisation, and 14 months for decreased tumor vascularisation; survival was 28 months for the group of increased, and 13 and 14 months for the normal and decreased tumor perfusion groups respectively. Also, response rates with 80%, 40%, and 75% responders in the group of increased, normal, and decreased tumor vascularisation, respectively, and 80%, 50%, and 59% responders in the group of increased, normal, and decreased perfusion, respectively, were not significantly different. These results indicate that there is no possibility to discriminate potential responders from nonresponders by results of liver angiography or perfusion scintigraphy.

Hepatic Artery↗