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Biomedical subjects

R Engelhardt

Publications and source records attributed to R Engelhardt.

At least 19 recordsLinked to original sources
PubMed2004

Interaction of artificial metallic objects with biosusceptometric measurements.

In human subjects, metallic objects cause distortions of the magnetic fields used by magnetic resonance imaging (0.5 - 3.0 T) or by SQUID biomagnetic liver susceptometry (0.1 - 30 mT) and may lead to artifacts in the measurement of the relaxation rate or the magnetic susceptibility. In biosusceptometry, the measured signal will depend not only on the magnetic susceptibility of the object, but also on its distance to the sensor assembly, and in case of ferromagnetic objects, on the direction of its remanent field. The magnetic susceptibility of a vascular access port-a-cath and of surgical clips have been measured by a SQUID biosusceptometer. Additionally, the impact from port-a-caths and dental braces on liver iron concentration (LIC) measurements was measured in vivo with respect to their radial distance from the gradiometer center axis. For the port-a-cath, a mean magnetic volume susceptibility of (83.5 +/- 0.3).10(-6) SI-units was found, which may be compared with the magnetic susceptibility of titanium at room temperature of (180 +/- 2).10(-6) SI demonstrating the absence of ferromagnetic contamination. At a radial distance of 5 cm from the gradiometer center axis, the voltage amplitude is similar to the signal generated by a normal liver. Modern surgical clips have nearly no impact on LIC measurements. However, dental braces although further away from the center axis, often superimpose the signal even from an iron overloaded liver. Depending on the Ni-content, these objects reveal ferromagnetic properties and contribute in first order with a one parameter reciprocal distance function to the measured liver iron signal.

Artifacts↗
PubMed2001

[Biomorphometry of corneal epithelium with slit lamp-adapted optical coherence tomography].

INTRODUCTION: The purpose of this study was to evaluate the biomorphometry of the corneal epithelium with slitlamp-adapted optical coherence tomography (OCT). PATIENTS AND METHODS: In a clinical study, slitlamp-adapted OCT of the cornea was performed in 15 patients before and immediately after therapeutic corneal abrasion. Central corneal epithelium thickness measurements were compared to the pre- and postoperative central corneal thickness. RESULTS: Preoperatively, the corneal epithelium could be visualised from the highest OCT light reflections at the interfaces air-tear film and epithelium-Bowman's membrane. The preoperative mean geometrical central epithelial thickness determined with OCT ranged from 65 +/- 12 microns to 72 +/- 14 microns (45-92 microns). The mean difference of the pre- and postoperative central corneal thickness was 48 +/- 19 microns (9-79 microns). This resulted in a deviation from the direct epithelial thickness measurements of 26-33%. The reproducibility of the geometrical epithelial thickness was +/- 9 microns. CONCLUSIONS: Slitlamp-adapted OCT enabled a noncontact evaluation of the corneal epithelium. The difference between direct and indirect corneal epithelium thickness measurements could be related to the partial optical inclusion of the precorneal tear film and the Bowman's membrane. With some restrictions the biomorphometry of the corneal epithelium with slitlamp-adapted OCT seems to be a valuable technique to monitor therapeutical and refractive procedures of the cornea.

Adult↗
PubMed2001

[Examination of the cornea using optical coherence tomography].

INTRODUCTION: This study evaluated the clinical use of optical coherence tomography (OCT) for two-dimensional representation of the cornea. PATIENTS AND METHODS: Noncontact slitlamp-adapted OCT was used in selected cases to evaluate pathologically altered corneas and to measure the central corneal thickness and curvature. RESULTS: OCT provided correlation between differences in reflection and morphological changes. Scar tissue resulted in hyper-reflective light scattering, whereas cystic lesions were hyporeflective. Precise biomorphometry also allowed representation of intrastromal and retrocorneal changes. Central corneal thickness measured by OCT yielded reproducible values and corneal curvature could be calculated from the optical signals of the corneal surface. CONCLUSIONS: OCT provides high-resolution representation of the cornea and exact evaluation of its morphology, thickness, and curvature. Due to the noncontact, simple, and rapid examination using the slitlamp the corneal OCT method is a promising additional diagnostic modality.

Adolescent↗
PubMed2000

Slit-lamp-adapted optical coherence tomography of the anterior segment.

PURPOSE: To evaluate the diagnostic potential of a slit-lamp-adapted optical coherence tomography (OCT) system as an in vivo imaging device for routine clinical examination of the anterior segment of the eye. PATIENTS AND METHODS: In a pilot study, healthy volunteers and patients with different pathologies of the anterior segment were examined with a slit-lamp-adapted OCT system using 100-200 axial scans with 100-Hz line-scan frequency. The scan length is variable up to 7 mm, and the axial depth is 1.5 mm in tissue. RESULTS: The slit-lamp-adapted OCT system allowed direct biomicroscopic imaging of the measured area. Anatomic structures and morphological changes anterior to the attenuating iris pigment epithelium could be visualized with high accuracy. Biometric analyses of the cornea, the chamber angle, the iris and secondary cataract were possible. Complete demonstration of the chamber angle was difficult due to the backscattering properties of the anterior part of the sclera and the consequent shadowing of the most peripheral part of the iris. CONCLUSIONS: Slit-lamp-adapted OCT is a useful diagnostic tool which allows in vivo microscopic cross-sectional imaging of the anterior segment and precise measurement of ocular structures.

Anterior Eye Segment↗
PubMed2000

Corneal optical coherence tomography before and immediately after excimer laser photorefractive keratectomy.

PURPOSE: To investigate the representation of the corneal structure with optical coherence tomography before and immediately after excimer laser photorefractive keratectomy. METHODS: Twenty-four eyes of 24 patients with myopia and myopic astigmatism were prospectively studied. The corneal thickness and the corneal profile were assessed with slit-lamp-adapted optical coherence tomography preoperatively and immediately after excimer laser photorefractive keratectomy. RESULTS: The attempted mean spherical equivalent of the refractive corrections was -6.7 +/- 3.6 (mean +/- SD) diopters with a mean calculated stromal ablation depth of 91 +/- 38 microm. The corneal optical coherence tomography was reproducible in all patients, demonstrating a mean decrease of central corneal thickness after epithelial debridement and excimer laser photorefractive keratectomy of 118 +/- 45 microm. The comparison of the calculated stromal ablation depth and the corneal thickness changes determined by corneal optical coherence tomography revealed a significant linear relationship with a correlation coefficient of 0.88 (P <.001). The flattening of the corneal curvature was confirmed in all patients with the optical coherence tomography system and correlated with the attempted refractive correction (r =.82, P <.001). CONCLUSIONS: The slit-lamp-adapted optical coherence tomography system presented in this study allowed noncontact, cross-sectional, and high-resolution imaging of the corneal configuration. This initial clinical evaluation demonstrated that corneal optical coherence tomography could be a promising diagnostic modality to monitor corneal changes of thickness and curvature before and after excimer laser photorefractive keratectomy.

Adult↗
PubMed2000

Self-organization and evolution in a simulated cross catalyzed network.

Motivated by an alternative to the concept of a prebiotic soup in the form of interacting crystal growth close to hot vents, we investigate a model system in which the growth rate of a particular entity is modified (enhanced or reduced) by other entities present, thus forming a web of cross catalysis. Initially random interactions are imposed, but the entities compete for a common source, and some entities may thus vanish in the competition. New entities, or mutations (error copies), with randomly selected interactions to the web are then introduced, and the concentrations of the entities are followed as solutions to stiff ordinary differential equations. Entities with positive growth may create new related entities with slightly randomly modified interactions to the web. Extinctions, wild-type survival and replacement, and self-organization to sustain periodic external variations, are studied. It is shown that even systems with mostly cross-inhibition and no initial autocatalysis may eventually create highly stable self-organized systems. We find that an already established cross catalyzed system often wins over a selfreplicating invader (or mutant).

Crystallization↗
PubMed1999

Assessment of iron stores in children with transfusion siderosis by biomagnetic liver susceptometry.

To investigate the applicability of noninvasive Superconducting Quantum Interference Device (SQUID) biomagnetic liver susceptometry and its limitations in thalassemic children, 23 patients with beta-thalassemia major and other iron loading anemias (age: 4-16 years) and 16 age-related normal children were studied. Liver iron concentrations ranged from 600 to 11,000 microg/g(liver) for thalassemic patients and from 60 to 340 microg/g(liver) for normal patients. Measuring the respective organ volumes by sonography, liver and spleen iron stores, accounting for 80% of total body iron stores, were estimated. Nonliver contributions from the lung or intestine to the measured SQUID signals in the small-sized patients were not observed. Moreover, livers in thalassemia were found to be enlarged by 18% per 1,000 microg/g (r = 0.75, P < 10(-3)). Serum ferritin values correlate significantly with iron stores (r = 0.64, P < 10(-3)), but predict iron stores only within large error intervals of 4,000 microg/g(liver). Analyzing the experimental data from biomagnetometry and from related transfusion and chelation treatment data within the framework of a two-compartment model, we were able to derive additional information on total body iron elimination and chelation therapy efficacy. The exponential decline of iron stores allows forecast of steady-state conditions of the final iron load for a particular transfusion and chelation therapy regimen.

Adolescent↗
PubMed1999

Standard- and high-dose etoposide, ifosfamide, carboplatin, and epirubicin in 100 patients with small-cell lung cancer: a mature follow-up report.

BACKGROUND: We conducted a phase I-II trial to assess the feasibility and activity of a combination chemotherapy regimen with etoposide, ifosfamide, cisplatin or carboplatin, and epirubicin in limited-disease (LD, stages I-IIIB) and extensive-stage (ED, stage IV) small-cell lung cancer (SCLC). PATIENTS AND METHODS: Standard-dose chemotherapy (SDC) consisting of etoposide (500 mg/m2), ifosfamide (4000 mg/m2), cisplatin (50 mg/m2) and epirubicin (50 mg/m2) (VIP-E), followed by granulocyte colony-stimulating factor (G-CSF), was given to 100 patients with SCLC. Thirty patients with qualifying responses to VIP-E proceeded to high-dose chemotherapy (HDC) with autologous peripheral blood stem-cell transplantation (PBSCT) after etoposide (1,500 mg/m2), ifosfamide (12,000 mg/m2), carboplatin (750 mg/m2) and epirubicin (150 mg/m2) (VIC-E) conditioning. RESULTS OF STANDARD-DOSE VIP-E: Ninety-seven patients were evaluable for response. The objective response rate was 81% in LD SCLC (33% CR, 48% PR; excluding patients in surgical CR) and 77% in ED SCLC (18% CR, 58% PR). The treatment-related mortality (TRM) of SDC was 2%. Two additional patients in CR from their SCLC developed secondary non-small-cell lung cancers (NSCLC), and both were cured by surgery. The median survival was 19 months in LD SCLC and 6 months in ED SCLC. The five-year survivals were 36% in LD and 0% in ED SCLC. RESULTS OF HIGH-DOSE VIC-E: HDC was feasible in 16% of ED-, and 58% of LD-patients. All HDC patients (n = 30) improved or maintained prior responses. Four patients died of early treatment-related complications (TRM 13%). Two additional patients in CR from their SCLC developed secondary malignancies (esophageal cancer, secondary chronic myelogenous leukemia). The median survivals were 26 months in LD SCLC, and 8 months in ED SCLC. The five-year survival was 50% in LD and 0% in ED SCLC. CONCLUSIONS: Despite high response rates, survival after VIP-E SDC and VIC-E HDC in patients with ED SCLC is not superior to that achieved with less toxic traditional regimens. The high five-year survival rates achieved with these protocols in LD SCLC probably reflect both patient selection (high proportion of patients with prior surgical resection) and the high activity of our chemotherapy regimen in combination with radiotherapy. A study comparing protocols using simultaneous radiation therapy and chemotherapy, and other dose-escalated forms of SDC with HDC is needed to further define the role of this treatment modality in SCLC. Given the high rate of secondary malignancies observed in patients in CR > 2 years in our study, close follow-up and early treatment of these neoplasms may contribute to maintaining overall survival in patients with SCLC.

Adult↗
PubMed1999

Standard- and high-dose etoposide, ifosfamide, carboplatin, and epirubicin in 107 patients with non-small-cell lung cancer: a mature follow-up report.

BACKGROUND: We conducted a phase I-II trial to assess the activity of standard-dose (SDC) and high-dose chemotherapy (HDC) with etoposide, ifosfamide, cis/carboplatin, and epirubicin (VIP-E, VIC-E) in 107 patients with limited-stage (LS, stage I-IIIB) and extensive stage (ES, stage IV) non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Updated results of a previously published trial are presented. RESULTS: Response rates and survival after VIP-E were comparable to those of other standard-dose combination chemotherapies in NSCLC. Treatment-related mortality (TRM) in SDC was 3% in LS-NSCLC, and 8% in ES-NSCLC. TRM was 4% in patients selected for HDC by response rate and performance score. Five-year survival in LS-NSCLC was 12% after SDC, and 18% after HDC; it was 0% for both treatment protocols in ES-NSCLC. CONCLUSIONS: The activity of VIP-E SDC and VIC-E HDC is not superior to that of established protocols in the treatment of NSCLC. In view of the toxicity and TRM associated with this protocol, less aggressive regimens should be preferred for most patients. Whether selected patients with chemosensitive disease could benefit from VIP-E SDC and/or VIC-E HDC in an adjuvant or neo-adjuvant setting could not be determined within the scope of this study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

A comparative efficacy trial in Germany in infants who received either the Lederle/Takeda acellular pertussis component DTP (DTaP) vaccine, the Lederle whole-cell component DTP vaccine, or DT vaccine.

BACKGROUND: The goal of the trial was to determine the efficacy of a multicomponent acellular pertussis vaccine against Bordetella illnesses in comparison with a whole-cell product and DT. DESIGN: In a randomized, double-blind fashion, 2- to 4-month-old infants received 4 doses of either DTP or DTaP vaccine at 3, 4.5, 6, and 15 to 18 months of age. The controls received 3 doses (3, 4.5, 15 to 18 months of age) of DT vaccine. The DTP vaccine was Lederle adsorbed vaccine (licensed in the United States) and DTaP was Lederle/Takeda adsorbed vaccine. Follow-up for vaccine efficacy started 2 weeks after the third dose (DTP/DTaP) and at the same age (6.5 months) in DT recipients. Reactogenicity of all doses of all three vaccines was documented by standardized parent diary cards. In addition, all subjects were monitored for respiratory illnesses and serious adverse events by biweekly phone calls. RESULTS: From May 1991 to January 1993, a total of 10 271 infants were enrolled: 8532 received either DTP or DTaP and 1739 received DT. Specific efficacy against B pertussis infections with cough >/=7 days duration was 83% (95% confidence interval [CI]: 76-88) and 72% (95% CI: 62-79) for DTP and DTaP, respectively; results for DTP and DTaP based on >/=21 days of cough with either paroxysms, whoop or posttussive vomiting (PWV) were 93% (95% CI: 89-96) and 83% (95% CI: 76-88), respectively. For DTaP vaccine, efficacy was higher after the fourth dose as compared with its efficacy after the third dose (78% vs 62% for cough >/=7 days and 85% vs 76% for cough >/=21 days with PWV). For DTP vaccine, efficacy was less varied after the third and fourth dose (78% vs 85% for cough >/=7 days and 93% vs 93% for cough >/=21 days with PWV). In contrast with DTP, the DTaP vaccine had some efficacy against B parapertussis infection (point estimate for cough >/=7 days: 31% [95% CI: -10-56]). All vaccines were generally well-tolerated. However, side reactions were significantly less after DTaP compared with DTP. CONCLUSIONS: Like other multicomponent acellular pertussis vaccines, the Lederle/Takeda DTaP vaccine demonstrated good efficacy against mild and typical pertussis due to B pertussis infections. Interestingly, it also may have some efficacy against B parapertussis. Based on the results of this trial, the vaccine was licensed in the United States in December 1996 for all 5 doses of the currently recommended immunization schedule in this country.

Bordetella Infections↗
PubMed1998

Multimodality treatment including early high-dose chemotherapy with peripheral blood stem cell transplantation in limited-disease small cell lung cancer.

Combined-modality treatment for limited-disease small cell lung cancer using conventional chemotherapy and chest irradiation achieves high response rates, but most patients relapse over a period of 12 to 16 months. To improve current results, we performed a phase II trial including high-dose chemotherapy and peripheral blood progenitor cell transplantation (PBPCT) as part of an early intensification strategy after two cycles of induction therapy. Moreover, to reduce the risk of local recurrence, the protocol included surgical resection in stages I to IIIA patients as well as chest irradiation. Between January 1991 and July 1994, 16 consecutive patients (median age, 50 years; age range, 30 to 59 years) were treated in this single-center trial. The patients received two cycles of conventional chemotherapy consisting of etoposide 500 mg/m2, ifosfamide 4 g/m2, cisplatin 50 mg/m2, and epirubicin 50 mg/m2 plus granulocyte colony-stimulating factor 5 microg/kg at a 3-week interval, followed by PBPC collection and subsequent high-dose etoposide 1,500 mg/m2, ifosfamide 12 g/m2, carboplatin 750 mg/m2, and epirubicin 150 mg/m2 with PBPCT. The duration of the entire chemotherapy program was 9 weeks. Six of 10 patients in stages I to IIIA and one of six patients in stage IIIB received neoadjuvant or adjuvant surgery before high-dose chemotherapy, followed by thoracic (50 Gy) and prophylactic (30 Gy) cranial irradiation. Hematopoietic reconstitution after high-dose chemotherapy occurred within 11 days (range, 9 to 17 days) for both neutrophils (>0.5 x 10(9)/L) and platelets (>20 x 10(9)/L). Oral mucositis (World Health Organization grade 2 to 4) was the predominant nonhematologic toxicity, which was observed in 12 of 16 patients. One patient developed neutropenic septicemia with fatal multiorgan failure. At a median follow-up of 44 months (range, 32 to 77 months) after PBPCT, nine patients are alive and well, resulting in a disease-free and overall survival rate of 56.3% +/- 12.4%. The median overall survival has not yet been achieved. None of the patients who had surgery relapsed or died after therapy. All relapses occurred within the first 12 months after PBPCT. Patients in stages I to IIIA (10 patients) had a 70% +/- 14% overall survival rate at 4 years, while patients in stage IIIB (six patients) had a 33% +/- 19% survival rate at 4 years, with a median survival of 17 months posttransplant. These data demonstrate that a multimodality treatment including early high-dose chemotherapy with PBPCT may lead to a prolonged disease-free survival in the majority of patients. A randomized phase III study has now been initiated to prospectively investigate the role of high-dose chemotherapy, surgery, and chest irradiation in the multidisciplinary approach to limited-disease small cell lung cancer.

Adult↗
PubMed1997

Downregulation of the proinflammatory cytokine response to endotoxin by pretreatment with the nontoxic lipid A analog SDZ MRL 953 in cancer patients.

Interfering with the endotoxin-mediated cytokine cascade is thought to be a promising approach to prevent septic complications in gram-negative infections. The synthetic lipid A analog SDZ MRL 953 has been shown to be protective against endotoxic shock and bacterial infection in preclinical in vivo models. As part of a trial of unspecific immunostimulation in cancer patients, we conducted a double-blind, randomized, vehicle-controlled phase I trial of SDZ MRL 953 to investigate, first, its biologic effects and safety of administration in humans and, second, its influence on reactions to a subsequent challenge of endotoxin (Salmonella abortus equi). Twenty patients were treated intravenously with escalating doses of SDZ MRL 953 or vehicle control, followed by an intravenous application of endotoxin (2 ng/kg of body weight [BW]). Administration of SDZ MRL 953 was safe and well-tolerated. SDZ MRL 953 itself increased granulocyte counts and serum levels of granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6), but not of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), IL-1beta, and IL-8. Compared with vehicle control, pretreatment with SDZ MRL 953 markedly reduced the release of TNF-alpha, IL-1beta, IL-8, IL-6, and G-CSF, but augmented the increase in granulocyte counts to endotoxin. Induction of tolerance to the endotoxin-mediated cascade of proinflammatory cytokines by pretreatment with SDZ MRL 953 in patients at risk may help to prevent complications of gram-negative sepsis.

Adjuvants, Immunologic↗
PubMed1997

Early-onset secondary malignancies after high-dose chemotherapy and autologous hematopoietic stem cell transplantation.

We treated 500 patients with high-dose chemotherapy (HDC) and autologous bone marrow (ABMT) or autologous peripheral blood stem cell transplantation (PBSCT). Treated conditions included leukemia, lymphomas, breast cancer, lung cancer, germ-cell carcinomas, and other solid tumors. In order to assess relapse of primary malignancy or occurrence of new neoplasms, routine screening after ABMT or PBPCT was performed at regular and close intervals. With a total follow-up of 1358 person-years and a median follow-up of 34 months (range 9-91), 10/500 (2%) patients developed second malignancies after PBSCT or ABMT; i.e., one new cancer occurred every 136 person-years. All malignancies were detected at routine follow-up examinations; and 7/10 diagnoses were made in an asymptomatic phase; 6/10 neoplasms were amenable to complete surgical resection, five of which remain in CR at a median of 23+ months after autotransplantation. We conclude that regular and close follow-up examination of patients after autologous hematopoietic stem cell transplantation may be beneficial, since successful treatment of second malignancies is possible in selected cases after early detection.

Adult↗
PubMed1997

High-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with second primary malignancies.

We treated 500 patients with high-dose chemotherapy and autologous bone marrow or autologous peripheral blood stem cell transplantation. Treated conditions included leukemia, lymphoma, breast cancer, lung cancer, germ-cell carcinoma, and other solid tumors. 10/500 (2%) of patients were treated for a second malignancy diagnosed 12 months to 25 years after their initial neoplasm. Four of these ten patients are in complete remission (CR) of both malignancies at a median follow-up of 29+ months after high-dose chemotherapy and autotransplantation. None of these patients would have been eligible for high-dose chemotherapy and autotransplantation by conventional selection criteria which usually excluded patients with a history of prior malignancies. Conclusion. Conventional exclusion criteria for high-dose chemotherapy and autotransplantation may not adequately reflect the prognosis of patients with second or secondary malignancies treated with this therapeutic modality. High-dose chemotherapy and autologous hematopoietic stem cell transplantation may be of true benefit in selected cases of secondary malignancies.

Adult↗