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Biomedical subjects

R Engelhardt

Publications and source records attributed to R Engelhardt.

At least 55 records · Page 3Linked to original sources
PubMed1994

Screening for hereditary hemochromatosis in prospective blood donors.

Prospective blood donors (n = 1,265, mean age 26 years) were screened for elevated serum ferritin and serum iron. Final diagnosis for hereditary hemochromatosis was made by liver iron concentration (noninvasive biomagnetometry), transferrin saturation, and 59Fe absorption in 3 male subjects. This preliminary result confirms for the first time the current frequency estimation of homozygous hemochromatosis (0.2-0.6%) in a group of young North-Germans.

Adult↗
PubMed1992

Induction of circulating phospholipase A2 activity by intravenous infusion of endotoxin in patients with neoplasia.

The purpose of this study was to evaluate the impact of repeated intravenous infusions of endotoxin (EN) in patients with cancer on the systemic release of extracellular proinflammatory phospholipase A2 (PLA2) and its relationship to the release of tumor necrosis factor (TNF) and interleukin-6 (IL-6). Six patients received 15 infusion of EN isolated from Salmonella abortus equi at a dose of 4 ng/kg. Marked increase in the activity of circulating PLA2 was noted within 3 h after the first EN infusion and reached a maximal level of 20.4-fold greater than baseline 24 h after infusion. In five patients challenged with EN 2 weeks later, PLA2 reached peak levels 15.5-fold greater than baseline. In two patients who received three sequential daily infusions, the incremental increase in PLA2 activity after the second and third challenge reached maximum levels 6 h after EN infusion. PLA2 response followed those of TNF and IL-6 but was quantitatively different. Whereas maximal levels of TNF and IL-6 declined substantially after repeat EN challenges, no such decline occurred in PLA2 activity. Since, in the clinical setting of gram-negative sepsis, there is recurrent increase in circulating EN, our study approximates this clinical situation and shows that extracellular release of PLA2 follows temporally that of proximal cytokines such as TNF and IL-6. These cytokines may be related to PLA2 release and sustained high activity in the systemic circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Noninvasive liver-iron quantification by computed tomography in iron-overloaded rats.

RATIONALE AND OBJECTIVES: The benefit of computed tomography (CT) for the noninvasive determination of liver-iron concentration in human iron-overload diseases is a controversy in the literature. To study the sensitivity of CT for liver-iron quantification under experimental conditions, the authors measured single- and dual-energy CT numbers in vivo in the livers of iron-overloaded rats. METHODS: Thirty-five rats were subjected to an iron-rich diet for various periods, from 1 to 20 weeks, then scanned by single- and dual-energy CT. CT absorption was correlated to liver-iron content, which was determined by wet ashing and spectrophotometry. RESULTS: Whereas a good correlation (r = 0.99 at 96 kV; r = 0.95 at 125 kV) between CT numbers and liver-iron concentration was found, CT was insensitive to low concentrations of iron. Dual-energy CT scanning results showed greater scattering in liver-iron quantification compared with single-energy CT. CONCLUSIONS: In rats, the sensitivity of single- and dual-energy CT is too low to quantify liver iron in the diagnostically most relevant region of mild liver siderosis (1-3 mg iron/g wet weight [w.wt]).

Animals↗
PubMed1991

Modulating activity of interferon-gamma on endotoxin-induced cytokine production in cancer patients.

Intravenous (IV) administration of purified lipopolysaccharide (LPS) from Salmonella abortus equi to cancer patients induces the formation of high amounts of endogenous cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). On repeated administration of LPS at 2-week intervals, a marked downregulation of the cytokine response was observed, especially between the first and the second challenge. This study sought to determine whether it would be possible to prevent this downregulation by pretreating patients with interferon-gamma (IFN-gamma), which is known to enhance cytokine production by monocytes and macrophages in vitro. Ten patients with disseminated cancer received a first injection of 4.0 ng LPS/kg. Thereafter, patients were divided into two groups. One group received two further LPS injections (4.0 ng/kg) at 2-week intervals. The second group was pretreated (-12 hours) with 50 micrograms IFN-gamma subcutaneously (SC) before the second and third LPS challenge. To prevent constitutional side effects such as fever and chills, patients received 1,600 mg ibuprofen orally before LPS injection. The results of the current study demonstrate that apart from TNF-alpha and IL-6, two other cytokines, interleukin-8 (IL-8) and granulocyte colony-stimulating factor (G-CSF) are produced in cancer patients in response to LPS. LPS application at 2-week intervals resulted in a transient attenuation of all cytokines (TNF-alpha, IL-6, IL-8, G-CSF) on the second challenge. In the case of TNF-alpha, IL-6, and G-CSF, pretreatment with IFN-gamma not only prevented the downregulation, but enhanced the production of these cytokines to levels higher than those obtained after the first LPS challenge. In contrast, the downregulation of IL-8 remained unaffected by IFN-gamma pretreatment. Further studies are warranted to determine whether the prevention of cytokine downregulation by IFN-gamma following repeated LPS injections is of clinical relevance in respect to the antitumor activity of LPS.

Adult↗
PubMed1991

Phase I trial of intravenously administered endotoxin (Salmonella abortus equi) in cancer patients.

We report a phase I study in cancer patients being treated with i.v. bolus injections of highly purified lipopolysaccharide (LPS) Salmonella abortus equi. Twenty-four patients with disseminated cancer received escalating doses of LPS at 2-week intervals. Dose escalation was performed in six dose levels treating 3-6 patients at each level. Dose levels 1 and 2 consisted of 0.15 and 0.3 ng/kg, respectively. Further dose escalation up to 5.0 ng/kg was enabled by pretreatment with ibuprofen, which attenuated the constitutional side effects of LPS. The maximum tolerated dose was 4.0 ng/kg with dose-limiting toxicity being World Health Organization grade III hepatic toxicity. Hematological changes included transient decreases in WBCs affecting granulocytes, monocytes, and lymphocytes in a marked different pattern. Endogenous cytokine release occurred in an LPS dose-dependent manner as measured by tumor necrosis factor-alpha, interleukin-6, and macrophage colony-stimulating factor serum levels. Moderate antitumor activity in colorectal cancer was observed in the case of 2 patients. Phase II trials of LPS are currently in progress.

Drug Administration Schedule↗
PubMed1991

A new concept for a realtime feedback system in angioplasty with a flashlamp pumped dye laser.

The feasibility of using a pulsed dye laser in angioplasty for detection and disintegration of calcified plaques was studied in vitro. A flashlamp-pumped dye laser (495 nm, 2 microseconds) was used as the exciting source for laser-induced-fluorescence (LIF) signals. Spectral data in the 520 nm to 800 nm region of normal intima, calcified plaque and fibro-fatty plaques were analyzed with an optical multichannel analyzer, using the same fiber for energy delivery and fluorescence diagnostic. Good signal to noise ratio and different spectra for different specimens were obtained within only 2 microseconds. The spectral difference is caused by selective reabsorption of oxyhemoglobin in the vessel wall. Time resolved LIF-spectroscopy shows that the fluorescence intensity reaches its maximum value before the maximum laser intensity is delivered. Fluorescence analysis can be performed in less than 300 ns and therefore the laser can be controlled before plasma threshold is reached. The described in vitro results can lead to a clinical useful feedbacksystem for energy control of microseconds lasers in angioplasty if the blood interference effects can be minimized by changing the laser excitation wavelength or staining the tissue.

Angioplasty, Laser↗
PubMed1991

Interspersion of fragmented fiber's splinters into tissue during pulsed alexandrite laser lithotripsy.

Laser induced shockwave lithotripsy (LISL) on artificially inserted human renal calculi was realized in explanted pig ureters. A pulse stretched Alexandrite solid state laser was used at 750nm. Pulses of 350ns and 1 microseconds duration were transmitted through a 250 microns all silica fiber onto a stone surface, keeping the fiber tip in contact with a stone close to the ureter wall. The high power density of the 350 ns pulses lead to an optical breakdown inside the distal fiber tip causing fiber fragmentation of about 28 mm/100 pulses. Deep penetration of the fiber fragments into the ureter wall was proven histologically. Fiber fragmentation was avoided by increasing the pulse duration up to 1 microseconds. Riks for patient treatment caused by short pulse lithotripsy are discussed.

Animals↗
PubMed1991

Treatment of cancer patients with endotoxin induces release of endogenous cytokines.

This study sought to determine whether endogenous tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and granulocyte-colony-stimulating factor (G-CSF) were detectable in sera of lipopolysaccharide (LPS)-treated cancer patients. Twenty patients received an intravenous bolus of purified LPS from Salmonella abortus-equi (4.0 ng/kg). Patients were pretreated with ibuprofen (1,600 mg) to prevent constitutional side effects like fever and chills. Serum TNF-alpha levels increased from less than 0.01 ng/ml before treatment up to maximal levels of 21 ng/ml, peaking 1.5 h after LPS injection. Similarly, serum IL-6 concentrations increased from less than 0.01 to 11 ng/ml, but peak levels were obtained 30 min later than TNF-alpha. Circulating G-CSF appeared still later than TNF-alpha and IL-6. It was detectable within 3 h and peaked 6 h after LPS injection. Parallel to the release of the above cytokines a marked increase in granulocyte counts was observed. In all patients administration of LPS led to an acute-phase response as measured by C-reactive protein.

Acute-Phase Reaction↗
PubMed1991

[Acute circulatory disorders of the eye. Clinical findings and results of Doppler sonography of the internal carotid artery].

Clinical and Doppler sonographic findings on the internal carotid artery of 218 patients with acute central retinal artery obstruction (42), branch retinal artery obstruction (43), anterior ischemic optic neuropathy (AION) (51), amaurosis fugax (AF) (21), and retinal vein occlusions (61) were evaluated. The most prominent finding was that only 1 out of 51 patients with AION and none of 61 patients with retinal vein occlusions showed a relevant stenosis or occlusion of the internal carotid artery. In contrast, however, patients with acute central retinal artery obstruction and branch retinal artery obstruction and those with AF revealed stenoses or occlusions of the internal carotid artery in approximative one-third to one-fourth of the cases. No excavation of the optic disc (cup) occurred in patients' eyes affected by AION or in the other eye. Fourteen of 51 patients with AION showed a "stuttering progression" of their visual function. The patients with progressive loss of vision were significantly younger on average than patients with permanent visual loss due to AION. Some of these cases with progressive field defects revealed an increase in edema of the optic discs and in hemorrhages. Patients with acute central retinal artery obstruction showed very high blood pressure values more often than patients with AION. Retinal emboli (Holenhorst plaques) were very often seen in patients with branch retinal artery obstruction (in 29 of 43 patients; 67%). However, they rarely occurred in patients with acute central retinal artery obstruction (5 of 42 patients). Only 1 of 51 cases with AION showed retinal emboli.

Adult↗
PubMed1990

[Colonic carcinoma localized in the chest in enterothorax due to congenital diaphragmatic hernia].

A 51-year-old man with congenital diaphragmatic hernia and enterothorax was found to have persisting leucocytosis (25,000/microliters), diarrhoea and weight loss (20 kg). Computed tomography (CT) revealed intrahepatic space-occupying lesions. CT-directed needle biopsy demonstrated adenocarcinoma metastases. Colon contrast enema was ambiguous. Since no primary tumour had been found, ambulatory treatment with 5-fluorouracil was started. After initial improvement diarrhoea and obstipation alternated so that the patient finally gave permission for coloscopy to which he had not consented at first. It revealed a carcinoma of the colon located in the thorax about 10 cm oral to the left colonic flexure. Progressive ileus necessitated an ileodescendostomy for palliation. The patient died three months later while on symptomatic treatment.

Adenocarcinoma↗
PubMed1990

Biological response to intravenously administered endotoxin in patients with advanced cancer.

The purpose of the study was to evaluate the toxicity and biological activity of highly purified lipopolysaccharide (LPS) administered intravenously to cancer patients in order to establish an optimum dosage scheme. An initial subtoxic dose was increased in weekly increments in accordance with individual regimens that maintained patient reaction at a safe and acceptable level. Purified LPS from Salmonella abortus equi was administered to 11 patients with advanced solid tumors on a weekly schedule with intraindividually escalating dosage as determined by patient response. Biological response was monitored by complete blood count, C-reactive protein, and cytokine measurements at different time points after LPS injection. Tumor necrosis factor-alpha (TNF) and interleukin-1 beta serum levels were measured by enzyme-linked immunosorbent assay and interleukin-6 (IL-6) by bioassay. Dose-limiting toxicities including chills and fever (WHO grade III) were reached at 1.0 ng/kg of body weight (maximal tolerated dose-1, MTD-1). Pretreatment with ibuprofen (1,600 mg) abrogated these side effects, allowing further escalation of LPS doses up to 10 ng/kg of body weight. At dose levels greater than 8.0 ng/kg of body weight (MTD-2), the aforementioned side effects occurred again and, additionally, hepatic toxicity (WHO grade III) was observed. Hematological changes included neutropenia followed by a pronounced neutrophilia contributed to by up to 30% bands, marked monocytopenia for 3 h, and retarded lymphopenia. By 24 h, all hematological parameters returned to pretreatment values. TNF serum levels increased from 10 pg/ml before treatment to 7,000 pg/ml as a function of dosage. Maximum serum levels were reached at 60 to 90 min after LPS injection. Similarly, IL-6 serum concentrations increased from less than 4 to 2,500 U/ml; peak levels were obtained 30 min after TNF peak values. Prior administration of ibuprofen had no effect on the above-mentioned hematological changes nor on cytokine release. LPS can be administered intravenously in weekly intervals at escalating doses from 0.15-10.0 ng/kg of body weight, when patients are protected by pretreatment with ibuprofen at dose levels above 1.0 ng/kg of body weight. Cytokine release as measured by TNF and IL-6 increased in a dose-dependent manner although the constitutional symptoms are completely attenuated.

Adult↗
PubMed1989

Treatment of human clonogenic tumor cells and bone marrow progenitor cells with bleomycin and peplomycin under 40.5 degrees C hyperthermia in vitro.

Tumor cells derived from 13 different individual human tumors were plated in a colony forming monolayer assay. The effect of bleomycin and peplomycin on colony formation was assessed in normothermic conditions and after a hyperthermic treatment at 40.5 degrees C for 2 h at the beginning of the culture. In three out of the 13 tumor samples (two colon carcinomas, one malignant melanoma), hyperthermic incubation resulted in a thermal enhancement of the effects of bleomycin and peplomycin. In addition, human bone marrow progenitor cells (CFU-C) were subjected to the same procedure. Peplomycin proved to be less toxic to CFU-C than bleomycin. In samples from eight different donors, homogeneous dose-response curves were observed. There was no difference between normo- and hyperthermic incubation.

Bleomycin↗
PubMed1988

Plasmablastic immunoglobulin-secreting lymphoma. Report of a case and a glimpse at the prognosis.

The case of a 57-year-old patient with a plasmablastic lymphoma is described. The primary diagnosis was an ordinary plasmacytoma, type IgG kappa. The final course of the disease involved almost all of the organs. The clinical aspect was determined by multiple skin infiltrations. The present report has in common with other published cases the fact that multiple secondary skin involvement of immunoglobulin-secreting tumors, regardless of their origin, have a very poor prognosis. In comparison, primary multiple cutaneous immunoglobulin-secreting tumors have a better prognosis.

Aged↗
PubMed1988

The pulsed dye laser versus the Q-switched Nd:YAG laser in laser-induced shock-wave lithotripsy.

To date, there are two fairly well-established alternatives for laser-induced shock-wave lithotripsy in clinical practice. The Q-switched Nd:YAG laser is distinguished by the high-stone selectivity of its coupler systems. The necessity of a coupler system and its fairly small conversion rate of light energy into mechanical energy present serious drawbacks. Furthermore, the minimal outer diameter of the transmission system is 1.8 mm. The pulsed-dye laser can be used with a highly flexible and uncomplicated 200-micron fiber. However, the laser system itself is more complicated than the Q-switched Nd:YAG laser and requires a great deal of maintenance. Biological evaluation of damage caused by direct irradiation shows that both laser systems produce minor damage of different degrees. YAG laser lithotripsy with the optomechanical coupler was assessed in 31 patients with ureteral calculi. The instability and limited effectiveness of the fiber application system necessitated auxiliary lithotripsy methods in 14 cases. Dye-laser lithotripsy is currently being tested in clinical application. Further development, such as systems for blind application or electronic feedback mechanisms to limit adverse tissue effects, have yet to be optimized. Nevertheless, laser-induced shock-wave lithotripsy has the potential to become a standard procedure in the endourologic management of stone disease.

Animals↗
PubMed1988

A rapid in vitro assay for predicting thermochemosensitivity of human cancer: comparison with clonogenic assay.

We previously reported a rapid in vitro assay based on morphological changes in the nucleus in order to predict response to thermochemotherapy. It was strongly suggested that this simple method may be clinically useful. In the present study, a comparison with the clonogenic assay was carried out on eight different human tumors (three malignant melanomas, two lung carcinomas, two colon carcinomas and one leukemia). Melphalan, mitomycin C and vincristine were tested. Correlation between the two test systems was dependent upon the criteria for each test system. At the level of less than 50% survival of colony as compared with normothermic dishes in clonogenic assay, there was a high correlation between the two test systems for sensitive tumor to 43 degrees C. In respect of response to thermochemotherapy, when only karyorrhexis changes in the nucleus were selected as an activity criteria in our cytotoxic test, parallel data between the two test systems were obtained.

Antineoplastic Agents↗