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Biomedical subjects

K Eichler

Publications and source records attributed to K Eichler.

At least 37 records · Page 2Linked to original sources

[Oligonodular hepatocellular carcinoma (HCC): MR-controlled laser-induced thermotherapy].

PURPOSE: To prospectively evaluate the therapeutic potential of MR-guided laser-induced thermotherapy (LITT) in patients with oligonodular hepatocellular carcinoma. MATERIAL AND METHODS: 39 patients with 61 intrahepatic lesions were treated with LITT. The Nd:YAG laser fiber was introduced with a percutaneously positioned irrigated laser application system. Qualitative and quantitative MR parameters and clinical data were evaluated. RESULTS: All patients tolerated the procedure well under local anesthesia. All observed complications were minor and no further treatment was necessary. Online MR thermometry allowed exact visualization. Lesions up to 2 cm in diameter could be efficiently treated with a single laser application, larger lesions were treated simultaneous multiapplication. In 97.5% we achieved a complete necrosis of the tumor and a 5 mm safety margin, resulting in a complete destruction of the tumor without local recurrences. Mean survival was 4.4 years (95% CI: 3.6-5.2 years) after the time of diagnoses of the HCC (Kaplan-Meier-method). CONCLUSION: In intrahepatic oligonodular involvement of hepatocellular carcinoma LITT appears to be an effective therapeutic procedure with a high tumor control rate and better survival data.

Adult↗

[Needle holder for reducing radiation burden of examiners in CT-assisted puncture. Technical contribution].

PURPOSE: To evaluate the use of a needle guide for CT guided puncture for the reduction of radiation dose of the interventional radiologist. MATERIAL AND METHODS: A total of 20 CT-guided punctures was performed. An approach from anterior was used in 12 cases and an approach from lateral was used in 8 cases. We evaluated the practicability, the precision and possible artifacts caused by the needle guide. RESULTS: All 20 punctures could be performed with the needle guide without any complications. We observed no artifacts on the images due to the needle guide. The ability to guide the puncturing needle was not affected by the needle guide. The use and the efficacy of the needle guide were best for the approach from anterior as well as a lateral approach. However, for angulated appraches from caudal to cranial there was no benifit regarding the distance of the hands of the interventional radiologist from the radiation beam of the CT unit. CONCLUSIONS: The use of the needle guide is reducing the radiation dose of the interventional radiologist during CT-guided punctures.

Biopsy, Needle↗

MR-guided laser-induced thermotherapy in recurrent extrahepatic abdominal tumors.

The aim of this study was to evaluate the feasibility of MR-guided laser-induced thermotherapy (LITT) for treatment of recurrent extrahepatic abdominal tumors. In 11 patients (6 women and 5 men; mean age 53 years, age range 29-67 years) with 14 lesions the following tumors were treated in this study: paravertebral recurrence of hypernephroma (n=1); recurrence of uterus carcinoma (n=1); recurrence of chondrosarcoma of the pubic bone (n=1); presacral recurrence of rectal carcinoma (n=1); recurrent anal cancer (n=1); metastases in the abdominal wall (n=1); and lymph node metastases from colorectal cancer (n=8). A total of 27 laser applications were performed. A fast low-angle shot 2D sequence (TR/TE/flip angle=102 ms/8 ms/70 degrees ) was used for nearly real-time monitoring during treatment. All patients had no other treatment option. Seventeen LITT sessions were performed using a conventional laser system with a mean laser power of 5.2 W (range 4.5-5.7 W), and 10 LITT session were performed using a power laser system with a mean laser power of 28.0 W. In 10 lesions total destruction could be achieved. In the remaining recurrent tumors, significant reduction of tumor volume by 60-80% was obtained. All patients tolerated the procedure well under local anesthesia. No complications occurred during treatment. Laser-induced thermotherapy is a practicable, minimally invasive, well-tolerated technique that can produce large areas of necrosis within recurrent tumors, substantially reducing active tumor volume if not resulting in outright destruction of tumor.

Abdominal Neoplasms↗

Laser-induced thermotherapy of malignant liver tumors: general principals, equipment(s), procedure(s)--side effects, complications and results.

PURPOSE: To prospectively evaluate the therapeutic potential of MR-guided and ultrasound-guided laser-induced thermotherapy (LITT) in patients with liver metastases and oligonodular hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Between June 1993 and June 2000 a total of 1608 LITT sessions was performed to treat 1914 lesions in 676 consecutive patients. The Nd-YAG laser fiber was introduced with a percutaneously positioned cooled application set. Qualitative and quantitative ultrasound and magnetic resonance (MR) parameters, as well as clinical data were evaluated. RESULTS: All patients tolerated the procedure well under local anesthesia; no relevant clinical complications were observed. The mean laser power was 25 W and the mean duration was 25 min. MR proved to be superior over computed tomography and ultrasound due the thermosensitivity of the MR sequences allowing a better visualization of the volume of laser-induced changes and their relation to the neighboring geographical structures. The ultrasound-guided LITT should be restricted for patients with contraindications for MR imaging monitoring and for selected patients with low diameter oligonodular HCC. In 95% of cases, we achieved a complete necrosis of the tumor and a 5-mm safety margin, resulting in a complete destruction of the tumor without local recurrences. Mean survival in this group was 35 months (calculated with the Kaplan-Meier method). CONCLUSION: MR-guided, or ultrasound-guided, LITT appears to be a safe and effective treatment protocol for liver metastases and oligonodular HCC.

Carcinoma, Hepatocellular↗

[Modern alternatives to resection of metastases--MR-guided laser-induced thermotherapy (LITT) and other local ablative techniques].

In patients with liver metastases of different primaries modern local ablative techniques such as laser-induced thermotherapy (LITT) and radiofrequency ablation (RF) are minimal invasive therapy options, if the patients were no candidates for liver surgery. A maximum of 5 cm lesion diameter and not more than 5 metastases without extrahepatic are treatable. MR-guided LITT is currently performed by means of implantable percutaneous catheter systems in local anesthesia and with outpatient management. RF is performed sometimes in general anesthesia and a hospital admission for some days. Liquid irrigated application systems are available both for LITT and for radiofrequency therapy and realized necrosis diameter up to 6 cm. At present LITT enables a local tumor control better than 98% for localized liver metastases without extrahepatic spreading patterns. In a group of 846 patients the average survival times were 4.0 years for patients with liver metastasis from different primary tumors. The data for RF ablation confirm the high value for tumor control for hepatocellular carcinomas with poorer results for liver metastases. Percutaneous MR-guided LITT permits good tumor control of liver metastases smaller than 5 cm and less than 5 in number with an improvement of survival times.

Carcinoma, Hepatocellular↗

[Percutaneous laser ablation of malignant liver tumors].

PURPOSE: To present the technical data, methods and results of percutaneous laser ablation of malignant tumors. PATIENTS AND METHODS: In the period from June 1993 to April 2000 a collective of 600 patients with malignant liver tumors and liver metastases from different primary tumors were treated via MR-guided LITT. After sonographically or CT-guided puncture MR-compatible laser catheters were positioned. The tumor destruction was visualized via MR-thermometry. The checkup and the therapy accomplishment ensued in the course of an ambulant therapy concept. RESULTS: In the course of a local accomplished LITT of liver metastases and malignant liver tumors a local tumor control rate of 97.8 % was achieved. The complication rate was extremely low with a value of 2.2 % (1 441 treatments). The lethality rate was 0.1 %. The mean survival time referring to the whole patient collective was 47.7 months, in the case of liver metastases from a colorectal cancer a value of 46.8 months was achieved. CONCLUSION: MR-guided LITT is a local effective therapy with low morbidity in malignant liver tumors with a maximum quantity of 5 and a size of </= 5 cm.

Adult↗

[Renal enhancement and excretion of the hepatobiliary contrast agent Gd-EOB-DTPA].

PURPOSE: To evaluate the clinical value of the renal clearance using MR imaging with different doses of gadolinium ethoxybenzyl-DTPA (Gd-EOB-DTPA) in comparison to gadolinium DTPA (Gd-DTPA). MATERIAL AND METHODS: In a double-blind and randomized clinical phase II study. MR imaging at 1.5 T was performed in 61 patients with five different doses of Gd-EOB-DTPA (3, 6, 12.5, 25 and 50 micromol/kg b. w. as a bolus injection). The study protocol comprised T(1)- and T(2)-weighted spin-echo magnetic resonance and two-dimensional fast low-angle shot imaging before and at increasing intervals for up to 45 min after injection of Gd-EOB-DTPA. These images were compared with Gd-DTPA-enhanced imaging (0.1 mmol/kg b. w. as a bolus injection). RESULTS: After bolus injection of the hepatobiliary MR contrast agent Gd-EOB-DTPA a renal elimination was observed. Immediately after the injection of Gd-EOB-DTPA until the eighth minute a corticomedullary enhancement of the kidney was conspicuous. After the fourth minute a contrast enhancement could be seen in the renal pelvis. The best enhancement was noted after 20 minutes in the FLASH GRE and T(1)-weighted images with good pelvicaliceal contrast. After 45 minutes an outflow of Gd-EOB-DTPA into the ureter could be observed. CONCLUSION: In addition to the hepatobiliary secretion Gd-EOB-DTPA appears useful for the evaluation of renal structures and renal function on account of the renal excretion without diuretic preparation of the patients.

Adult↗

[Percutaneous interstitial thermotherapy of malignant liver tumors].

PURPOSE: Description of local ablative techniques such as laser-induced thermotherapy (LITT) and radiofrequency ablation in the percutaneous interstitial thermotherapy for malignant liver tumors. PATIENTS AND METHODS: MR-guided LITT is currently performed by means of implantable percutaneous catheter systems. CT is used to control the insertion of the catheter. Irrigated administration systems are available both for LITT and for radiofrequency therapy. RESULTS: At present LITT enables a local tumor control of 97.2% for localized liver metastases without extrahepatic spreading patterns. In a group of 381 patients the average survival times were 45.7 months for patients with liver metastasis, 42.7 months for those with colorectal liver metastases, and 32 months for HCC tumors. The data for radiofrequency ablation confirm the high value for tumor control of hepatocellular carcinomas with poorer results for liver metastases. CONCLUSIONS: Percutaneous, MR-guided LITT permits good tumor control of liver metastases smaller than 5 cm and less than 5 in number. For HCC, at present percutaneous injection of alcohol, radiofrequency ablation, and LITT are equally effective.

Breast Neoplasms↗

[CT-guided percutaneous intratumoral chemotherapy with a novel cisplatin/epinephrine injectable gel for the treatment of inoperable malignant liver tumors].

PURPOSE: To evaluate prospectively the volumetric changes of tumor and necrosis in unresectable malignant liver tumors and the clinical aspects after CT-guided direct intratumoral administration of a novel cisplatin/epinephrine injectable gel in a clinical phase II study. PATIENTS AND METHODS: 8 patients with 17 colorectal liver metastases with a mean volume of 42 ml were treated with a mean of 5.1 injections and 8 patients with 11 HCC nodules (mean volume of 22.1 ml) with a mean of 3.25 treatments with CT-guided local administration of a novel cisplatin/epinephrine gel. This method of administration provides a higher local and lower systemic drug concentration. Volumes of tumor and necrosis prior to and after treatment were measured by computer-generated volumetric analysis. RESULTS: Contrast-enhanced studies verified pretherapeutic tumor necrosis with a value of 12.6% in the metastases and 0.6% in the HCC nodules. Intratumoral drug administration resulted in a necrotic volume of 110% in metastases and 128% in HCC versus the mean initial tumor volume, at least 4 treatments resulted in 122% necrosis in metastases and 130% in HCC. Local therapy control rate for the follow-up to 6 months was 38% and 83.3% for the group of metastases and HCC, respectively. CONCLUSIONS: Direct intratumoral injection of a novel cisplatin/epinephrine injectable gel results in an induction of a relevant necrosis in malignant liver tumors, with a substantially higher local therapy control rate for HCC compared to colorectal metastases.

Adult↗

[Interventional MR-guided laser induced thermotherapy in oncologic indications. Status and prospects].

MR-guided LITT (laser-induced thermotherapy) is currently being evaluated for its effectiveness in clinical oncology. MR-guided LITT is defined as a minimally invasive technology based on the effects of the applied Nd-YAG laser on tumorous tissue. Due to specific characteristics of the laser-induced coagulative effect, online monitoring via MR thermometry is possible and extremely precise. In a period of 6 years 335 patients suffering from malignant soft tissue tumors were prospectively treated via MR-guided LITT. We evaluated the local tumor control rate, the rate of complications and the survival data from the clinical and MRI follow-up. Our results prove that MR-guided LITT results in a extremely low rate of side effects and an effective tumor control rate higher than 95%, depending on the size of the lesion. It is concluded that this therapeutic concept is of clinical value for patients with primary and secondary liver cancer, malignant lymph node involvement, abdominal recurrent tumors and tumors of the head and neck.

Adult↗

Interventional MR: interstitial therapy.

The rationale and results for interstitial therapies via interventional MRI in the treatment of tumors in various regions are presented. Different interstitial treatment techniques are presented based on varying technologies both for tumor ablation and treatment monitoring. Data are presented based on 335 patients, 29-84 years of age (mean age 59 years, 196 men and 139 women) with a total of 932 liver tumors, 16 head and neck tumors and 14 abdominal recurrent pelvic and lymphatic tumors. All lesions had been treated with MR-guided laser-induced interstitial thermotherapy (LITT) via 2516 laser applications and 1856 cannulations. Data in the literature are extremely varying depending on author experience, treatment technique, and the included patient material. In our patient material we were able to achieve a local tumor control of 96.7% depending on the size of the tumorous lesion, the topographical relationship, and the applied laser parameters. The overall cumulative survival rate of patients with liver metastases was 45.74 months (median 40.97 months, 95 % confidence interval 31.42-50.52). The cumulative survival rate of the patient group with hepatic metastases of colorectal carcinoma was 42.71 months (median 39.33 months, 95% confidence interval 33.26-45.37). In patients with head and neck tumors a relevant reduction in clinically relevant symptoms such as pain, swallowing disorders, or nervous compression was achieved in 11 of 15 patients treated with LITT. In 14 soft tissue tumors, such as pelvic tumor recurrence and lymph node metastases, a local tumor control was obtained in 68% of lesions. Interstitial therapies under interventional MRI guidance, such as LITT, results in a high local tumor control with an improved survival rate.

Abdominal Neoplasms↗

Positive co-regulation of the Escherichia coli carnitine pathway cai and fix operons by CRP and the CaiF activator.

Activation of the two divergent Escherichia coli cai and fix operons involved in anaerobic carnitine metabolism is co-dependent on the cyclic AMP receptor protein (CRP) and on CaiF, the specific carnitine-sensitive transcriptional regulator. CaiF was overproduced using a phage T7 system, purified on a heparin column and ran as a 15 kDa protein on SDS-PAGE. DNase I footprinting and interference experiments identified two sites, F1 and F2, with apparently comparable affinities for the binding of CaiF in the cai-fix regulatory region. These sites share a common perfect inverted repeat comprising two 11 bp half-sites separated by 13 bp, and centred at -70 and -127 from the fix transcription start site. They were found to overlap the two low-affinity binding sites, CRP2 and CRP3, determined previously for CRP. Gel shift assays and footprinting experiments suggest that CaiF and CRP bind co-operatively to the F1/CRP2 and F2/CRP3 sites of the intergenic cai-fix region. Moreover, they appeared to serve the simultaneous binding of each other, giving rise to an original multiprotein CRP-CaiF complex enabling RNA polymerase recruitment and local DNA untwisting, at least at the fix promoter. Using random mutagenesis, two CaiF mutants impaired in transcription activation were isolated. The N-terminal A27V mutation affected the structural organization of the activator, whereas the central I62N mutation was suggested to interfere with DNA binding.

Bacterial Proteins↗

Regulation of the carnitine pathway in Escherichia coli: investigation of the cai-fix divergent promoter region.

The divergent structural operons caiTABCDE and fixABCX of Escherichia coli are required for anaerobic carnitine metabolism. Transcriptional monocopy lacZ fusion studies showed that both operons are coexpressed during anaerobic growth in the presence of carnitine, respond to common environmental stimuli (like glucose and nitrate), and are modulated positively by the same general regulators, CRP and FNR, and negatively by H-NS. Overproduction of the CaiF specific regulatory protein mediating the carnitine signal restored induction in an fnr mutant, corresponding to its role as the primary target for anaerobiosis. Transcript analysis identified two divergent transcription start points initiating 289 bp apart. DNase I footprinting revealed three sites with various affinities for the binding of the cAMP-CRP complex inside this regulatory region. Site-directed mutagenesis experiments indicated that previously reported perfect CRP motif 1, centered at -41.5 of the cai transcriptional start site, plays a direct role in the sole cai activation. In contrast, mutation in CRP site 2, positioned at -69.5 of the fix promoter, caused only a threefold reduction in fix expression. Thus, the role of the third CRP site, located at -126.5 of fix, might be to reinforce the action of site 2. A critical 50-bp cis-acting sequence overlapping the fix mRNA start site was found, by deletion analysis, to be necessary for cai transcription. This region is thought to be involved in transduction of the signal mediated by the CaiF regulator.

Acyltransferases↗

New markers on bovine chromosome 1 are closely linked to the polled gene in Simmental and Pinzgauer cattle.

In this study, four new markers located on bovine Chromosome 1 were tested for linkage with the polled condition in the Simmental and Pinzgauer breeds. The microsatellites INRA212 (D1S42) and the gene for keratin-associated protein 8 (KAP8) show significant linkage with polled at theta = 0.00 (Lod = 6.92), and theta = 0.033 (Lod = 6. 52) respectively. The microsatellite INRA117 (D1S20) and the gene for interferon-alpha receptor (IFNAR) show maximum Lod scores of 2.1 and 1.8 at a recombination rate of zero.

Animals↗

Identification and characterization of the caiF gene encoding a potential transcriptional activator of carnitine metabolism in Escherichia coli.

Expression of the Escherichia coli caiTABCDE and fixABCX operons involved in carnitine metabolism is induced by both carnitine and anaerobiosis. When cloned into a multicopy plasmid, the 3' region adjacent to the caiTABCDE operon was found to increase levels of carnitine dehydratase activity synthesized from the chromosomal caiB gene. The nucleotide sequence was determined, and it was shown to contain an open reading frame of 393 bp named caiF which is transcribed in the direction opposite that of the cai operon. This open reading frame encodes a protein of 131 amino acids with a predicted molecular mass of 15,438 Da which does not have any significant homology with proteins available in data libraries. In vivo overexpression consistently led to the synthesis of a 16-kDa protein. The caiF gene was transcribed as a monocistronic mRNA under anaerobiosis independently of the presence of carnitine. Primer extension analysis located the start site of transcription to position 82 upstream of the caiF initiation codon. It was preceded by a cyclic AMP receptor protein motif centered at position -41.5. Overproduction of CaiF resulted in the stimulation of transcription of the divergent cai and fix operons in the presence of carnitine. This suggested that CaiF by interacting with carnitine plays the role of an activator, thereby mediating induction of carnitine metabolism. Moreover, CaiF could complement in trans the regulatory defect of laboratory strain MC4100 impaired in the carnitine pathway. Expression of a caiF-lacZ operon fusion was subject to FNR regulator-mediated anaerobic induction and cyclic AMP receptor protein activation. The histone-like protein H-NS and the NarL (plus nitrate) regulator acted as repressors. Because of the multiple controls to which the caiF gene is subjected, it appears to be a key element in the regulation of carnitine metabolism.

Acyltransferases↗

The fix Escherichia coli region contains four genes related to carnitine metabolism.

Anaerobic carnitine metabolism in Escherichia coli was recently shown to involve six genes organized in the cai operon and located at the first minute on the chromosome. The DNA sequence lying at the 5' end of the cai locus was further investigated. It contains four open reading frames organized as an operon. In vivo overexpression of this DNA region revealed four polypeptides with apparent molecular masses of 27, 33, 45 and 6 kDa. These proteins displayed significant amino acid sequence homologies with polypeptides encoded by the fixABCX operons from Azorhizobium caulinodans and Rhizobium meliloti. The four ORFs were thus named fixABCX. The first two gene products were also found to share a high degree of sequence similarity with the subunits beta and alpha, respectively, of mammalian electron transfer flavoproteins, suggesting a role for these proteins in a redox reaction. A singly polycistronic 5 kb mRNA transcript was detected in Northern blots under anaerobic conditions in the presence of DL-carnitine. Expression of a fixA-lacZ transcriptional fusion was induced by L(-)-carnitine and crotonobetaine but not by D(+)-carnitine, gamma-butyrobetaine, glycinebetaine and choline as found previously for the carnitine pathway. Similarly, the fix operon was repressed by glucose and nitrate. Moreover, expression of the fix operon was induced by the global regulatory proteins CRP and FNR and repressed by the histone-like protein H-NS. All these regulatory proteins have been shown also to control expression of carnitine enzymes. Results from Northern blots and lacZ fusion studies indicate a common regulation of expression of fix and cai operons, which implies a physiological linkage between these two loci.

Anaerobiosis↗