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Biomedical subjects

H Menzel

Publications and source records attributed to H Menzel.

At least 19 recordsLinked to original sources
PubMed2007

The RBE issues in ion-beam therapy: conclusions of a joint IAEA/ICRU working group regarding quantities and units.

This paper summarises the conclusions of a working group established jointly by the International Atomic Energy Agency (IAEA) and the International Commission on Radiation Units and Measurements (ICRU) to address some of the relative biological effectiveness (RBE) issues encountered in ion-beam therapy. Special emphasis is put on the selection and definition of the involved quantities and units. The isoeffective dose, as introduced here for radiation therapy applications, is the dose that delivered under reference conditions would produce the same clinical effects as the actual treatment in a given system, all other conditions being identical. It is expressed in Gy. The reference treatment conditions are: photon irradiation, 2 Gy per fraction, 5 daily fractions a week. The isoeffective dose D(IsoE) is the product of the physical quantity absorbed dose D and a weighting factor W(IsoE). W(IsoE) is an inclusive weighting factor that takes into account all factors that could influence the clinical effects like dose per fraction, overall time, radiation quality (RQ), biological system and effects. The numerical value of W(IsoE) is selected by the radiation-oncology team for a given patient (or treatment protocol). It is part of the treatment prescription. Evaluation of the influence of RQ on W(IsoE) raises complex problems because of the clinically significant RBE variations with biological effect (late vs. early) and position in depth in the tissues which is a problem specific to ion-beam therapy. Comparison of the isoeffective dose with the equivalent dose frequently used in proton- and ion-beam therapy is discussed.

Heavy Ion Radiotherapy↗
PubMed2005

[Improved osseointegration of titanium implants after surface coating with polymers in a rabbit model].

In this study we present the first results of the investigation of polymer-coated titanium implants implanted in the proximal tibia and distal femora of New Zealand white rabbits. The results of DEXA scans, micro-CT, and histological analysis showed an increase of osseointegration. We suggest that controlled release kinetics after coupling of these polymers with BMP-2 can additionally increase osseointegration.

Animals↗
PubMed2005

Lasting remission following multimodal treatment in a patient with metastatic breast cancer.

We report on a lasting remission from multimodal treatment in a patient with hepatic metastasized breast cancer. After surgical removal of a singular hepatic metastasis, the patient underwent leukapheresis of peripheral blood mononuclear cell (PBMCs). For induction chemotherapy, the patient received 2 cycles of epirubicin and paclitaxel (ET). After 1 cycle of epirubicin and ifosfamide (EI), peripheral blood stem cells were harvested. After a final cycle of ET, the patient underwent high-dose chemotherapy (HDCT; thiotepa 600 mg/m/melphalan 180 mg/m) and autologous stem cell transplantation. Once reconstitution was achieved, PBMCs were reinfused followed by i.v. application of a trifunctional antibody (TrAb) with specificities anti-EpCAMxanti-CD3. TrAbs are able to simultaneously bind tumor cells, T cells, and additionally FcgammaR type I and III+accessory cells via their Fc region. Side-effects during treatment were hematotoxicity, mucositis and gastrointestinal toxicity. TrAb treatment resulted in intermittent fever, chills, elevated liver enzymes, systemic inflammatory response syndrome and pulmonary leakage. With a follow-up period of more than 8 years the patient is still in remission (96+months). This case suggests the feasibility and efficacy of combining surgery, standard and HDCT, and subsequent immunotherapy in metastatic breast cancer. Further investigation of this approach is indicated in a subgroup of patients with oligometastatic breast cancer.

Adult↗
PubMed2004

CYP1A1 alleles in women with focal nodular hyperplasia of the liver (FNH).

OBJECTIVE: Disorders of steroid hormone metabolism might be related to the etiology of focal nodular hyperplasia of the liver (FNH), a benign tumor, especially prevalent in women. The cytochrome P450 1A1 (CYP1A1) enzyme is implicated in the bioactivation of multiple precarcinogens as well as in the metabolism of steroids. Genetic polymorphisms of CYP1A1 have been associated with altered catalytic activity in the hydroxylation of sex hormones and this may account for interindividual variability in exposure to hormone-mediated cell proliferation signals and reactive steroid metabolites. In the study at hand, we aimed to evaluate a possible association between CYP1A1*1, *2A, *2B, and *4 alleles and FNH. METHOD: Genotyping of 26 affected female patients of Caucasian origin was carried out using PCR/RFLP. RESULTS: Allele frequencies for the CYP1A1 variants *2A, *2B and *4 in 26 female patients with FNH were 0.058, 0.019 and 0.058, respectively. Crude odds ratios for the individual alleles were 0.75 (95% CI 0.23-2.44), 0.72 (95% CI 0.10-5.34) and 1.96 (95% CI 0.59-6.50), respectively. There were no significant differences between these values and corresponding allele frequencies obtained in a large German sample of unaffected Caucasian women. CONCLUSION: The present data do not suggest a relevant association between CYP1A1 polymorphisms and focal nodular hyperplasia of the liver in female Caucasians.

Adult↗
PubMed2000

B-cell lymphoma idiotypes chimerized by gene targeting can induce tumor immunity.

Immunization with modified immunoglobulin (Ig) idiotypes (Ids) of B-cell lymphomas is an attractive approach of experimental tumor immunotherapy. We show here that B-lymphoma cells can be gene-modified by homologous recombination at the Ig heavy chain locus. Although it has been demonstrated previously that a protein vaccine containing a mouse/human chimeric Ig had no immunostimulatory effect, we show that a xenogeneic Fc segment attached to the Id by gene targeting in autologous murine tumor cells can serve as an immunogenic carrier and is capable of inducing tumor protection. A prerequisite for successful vaccination is the delivery of tumor cells that have been engineered to express the Id in the chimeric form rather than administration of the soluble chimeric protein. Also DNA vaccination with plasmids encoding chimeric Ids was reported to induce an anti-idiotypic response, suggesting that there might be related mechanisms such as enhanced antigen presentation. Immunization with engineered lymphoma cells is a very potent protocol: in the cell-based setting, minute levels of expression in the gene-targeted cells are sufficient to confer tumor immunity. Because the titers of anti-Id antibodies induced do not reflect the degree of tumor protection, the immune mechanisms responsible for tumor rejection cannot be ascribed exclusively to a humoral response.

Adoptive Transfer↗
PubMed1999

Induction of tumor immunity by autologous B lymphoma cells expressing a genetically engineered idiotype.

A fusion protein containing a B cell lymphoma idiotype (Id) and granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent stimulator of tumor immunity. In three different tumor models we show that immunization with autologous lymphoma cells that have been engineered to express the Id in the context of GM-CSF is much more effective than immunization with an equivalent dose of the purified protein. The lymphoma Id could be modified by introducing the GM-CSF gene into the immunoglobulin (Ig) heavy chain locus via gene targeting. This approach circumvents the isolation of the rearranged immunoglobulin variable genes from the tumor and the preparation of tumor-specific vector constructs. The low production of Id/GM-CSF fusion proteins by transfected cells, which is a major obstacle in the use of purified fusion proteins for immunotherapy, is due to the presence of the cytokine gene in the immunoglobulin locus. Low production, however, is not limiting in the cell-based setting, because upon in vivo administration of the modified autologous cells, even minute expression levels are sufficient to induce tumor immunity.

Animals↗
PubMed1997

Effects of a low selenium state in patients with phenylketonuria.

Eighty-seven participants of the German Collaboratory Study for Children with Phenylketonuria (PKU) presented low plasma, whole blood and hair selenium (Se) values, reduced urinary selenium excretion, and decreased plasma and erythrocyte glutathione peroxidase activity in comparison with a healthy reference group (all figures p < 0.001). Aspartate amino transferase and thyroxine (T4) concentrations in plasma were inversely correlated with the selenium blood values of the PKU children. Somatic measurements showed a negative standard deviation score of body height in the PKU children compared with reference values. Despite the different Se supply, the infants did not present any specific Se deficiency symptoms.

Adolescent↗
PubMed1996

Bispecific antibodies target operationally tumor-specific antigens in two leukemia relapse models.

Despite improved procedures in chemotherapy and bone marrow transplantation (BMT), post-BMT leukemia relapse rates have remained rather constant in the last decade. Immunotherapy with monoclonal or bispecific antibodies (bsAb) is a promising approach to improve this situation, but is hampered by the absence of tumor-specific antigens on the majority of tumors. To evade this problem, we developed a new tumor-specific approach in which bispecific antibodies exploit chimerism after allogeneic BMT by redirecting donor T cells against recipient-specific antigens on tumor cells. Two different leukemia relapse models were established using a T-cell lymphoma (ST-1) and a B-cell lymphoma (BCL1) to evaluate the efficiency of such a therapy. In these experiments, irradiated BALB/c (Thy-1.2+, I-Ad) mice were transplanted with C57BL/6 Thy-1.1 (I-Ab) BM cells under the protection of graft-versus-host disease-preventing monoclonal antibodies. Forty-five days after BMT, the chimeric mice were injected with either 2 x 10(4) recipient-type, Thy-1.2+, CD3- ST-1 cells or major histocompatability complex (MHC) class II+ (I-Ad)-BCL1 cells. Four days later, the mice were treated with 8 microg bsAb G2 (anti-CD3 x anti-Thy-1.2) or 10 microg (+10 microg, day 6) bsAb BiC (anti-CD3 x anti-I-Ad), respectively. These combinations guaranteed exclusive binding of the bsAbs target arms to tumor cells, leaving the surrounding, donor-type hematopoietic cells unbound. Compared with the parental antibodies, the bsAbs markedly reduced tumor mortality. Between 34% and 83% of mice survived in the bsAb groups compared with 0% of the control groups treated with parental antibodies, clearly documenting the benefit of the redirection principle. Furthermore, cytokine release (interleukin-6) after anti-CD3 antibody or bsAb treatment was decreased by administering a low-dose antibody preinjection. We have shown (1) that 6 weeks after BMT, when donor T-cell reconstitution is still in progress, T-cell-redirecting bsAb are clearly superior to parental antibodies in terms of tumor cell elimination; and (2) that the polymorphism of a common antigen such as Thy-1 or a clinically more relevant target antigen such as MHC class II can be used as an operational tumor-specific antigen after allogeneic BMT.

Animals↗
PubMed1996

Selenium and glutathione peroxidase activity in Hungarian children.

Selenium (Se) in plasma, whole blood and erythrocytes as well as glutathione peroxidase (GSH-Px) activity in plasma and erythrocytes were investigated in 161 healthy Hungarian children aged 1-15 years. Se was determined by AAS with hydride generation. The estimation of GSH-Px activity was performed in plasma with tertbutyl-hydroperoxide (t-BOOH) and in erythrocytes with hydrogen peroxide (H2O2) as acceptor substrates. The Se content in plasma (0.63 +/- 0.12 mumol/L), whole blood (0.81 +/- 0.14 mumol/L) and erythrocytes (1.14 +/- 0.26 mumol/L, the GSH-Px activity in plasma (87 +/- 19 U/L) and erythrocytes (5.93 +/- 1.04 U/gHb) was low in Hungarian children in comparison to values for children from other European countries. Samples from a rural area in southeast Hungary showed even lower Se content than samples from an industrial city in the northwest or from the capital. The Se in plasma and whole blood as well as GSH-Px activity in the plasma exhibited a clear age dependency. There was a good correlation between plasma Se and GSH-Px activity in all children (r = 0.633, p < 0.001). In addition, in children from the northwestern city and from the capital a correlation was found between Se content and GSH-Px activity of erythrocytes (r = 0.625, p < 0.001). There is no indication that the high mortality in young Hungarian adults from cardiovascular diseases is mainly caused by a low Se supply because there are no corresponding findings in the surrounding countries of southeastern or central eastern Europe with similar low Se states.

Adolescent↗
PubMed1995

Trace mineral status of full-term infants fed human milk, milk-based formula or partially hydrolysed whey protein formula.

Plasma zinc, copper, and selenium concentrations were determined in 129 full-term infants at birth and at the age of four months by electrothermal or hydride generation atomic absorption spectrometry. Of these, 49 infants were exclusively breast-fed (HM), 45 received various commercially available cow's milk formulae (F) and 35 infants were fed partially hydrolysed whey protein formula (PHF). The results were correlated with hematological, biochemical and somatic data. Plasma zinc values decreased from birth to the age of four months in all three groups (p < 0.001). The plasma Zn level of the babies fed PHF were similar to those of breast-fed infants, whereas in F-fed children the zinc values were significantly lower (PHF, 807 +/- 106; HM, 794 +/- 112; F, 725 +/- 111 micrograms l-1; all the measurements were performed at the age of four months). In infants fed PHF formula there was a negative correlation between plasma zinc and weight or height increments. In agreement with the literature, plasma copper and ceruloplasmin increased significantly within the first four months of life. The plasma copper content was similar in either feeding group. Plasma selenium was low at birth (40 +/- 9 micrograms l-1) and remained constant in breast-fed infants. In infants on PHF there was a steeper decline of plasma Se (20 +/- 6 micrograms l-1) than in infants fed cow's milk formula (29 +/- 9 micrograms l-1). Other parameters of the Se status showed a similar pattern. Despite the different zinc, copper, and selenium supply, plus presumedly different bioavailability, all the infants thrived.(ABSTRACT TRUNCATED AT 250 WORDS)

Copper↗
PubMed1995

Selenium in German infants fed breast milk or different formulas.

At birth and at 4 months of age, selenium (Se) values of 129 term infants on three different diets were determined: 50 infants were breast fed (HM), 44 received formula based on cow's milk (F) and 35 were fed "hypoallergenic formula" (PHF) (partially hydrolysed whey protein). The Se status of a group of twins (n = 12) fed "hypoallergenic formula" was compared with the respective group of singletons. All infants had low plasma Se values during early infancy. The plasma Se of breast-fed infants remained stable (plasma Se 43 +/- 8 ng/ml at birth and at 4 months), whereas plasma glutathione peroxidase (GSH-Px) decreased (birth: 107 +/- 29 U/l; 4 months: 62 +/- 11 U/l). The formula-fed infants showed a reduction in plasma Se levels from birth to 4 months (38 +/- 10 ng/ml and 29 +/- 9 ng/ml, respectively). The decrease was even more pronounced in infants fed the "hypoallergenic formula". This group presented the lowest Se values (plasma Se 39 +/- 9 ng/ml at birth; 20 +/- 6 ng/ml at 4 months). Renal excretion of Se was found to be lower in the formula-fed infants (F and PHF) compared with the HM group. There was a significant correlation between plasma and urinary Se (r = 0.62, p = 0.0001). Urinary Se (microgram Se/g creatinine) appeared to be a good indicator of Se intake. Measurements of urine Se might be used as a screening method for the estimation of the Se supply. Weight and length increases in all infants were within the normal range. There were no differences between the different feeding groups.

Bottle Feeding↗
PubMed1993

Selenium status and lipoproteins in healthy and diabetic children.

Selenium and the selenium-dependent glutathione peroxidase (GSH-Px) were measured in healthy and diabetic children from Germany and Hungary. Hyperglycemia and hyperlipidemia are present in diabetes mellitus and they are associated with increased lipid peroxidation. The selenium content of erythrocytes, whole blood and plasma, as well as of plasma glutathione peroxidase activity, were found to be low in the healthy Hungarian children compared to the healthy Germans. Both groups of diabetics had significantly higher blood selenium (1.05 +/- 0.14 versus 0.86 +/- 0.1 mumol/L in Hungarians, 1.34 +/- 0.21 versus 1.12 +/- 0.22 mumol/L in Germans) and higher plasma selenium (0.89 +/- 0.15 versus 0.68 +/- 0.01 mumol/L in Hungarians and 1.01 +/- 0.2 versus 0.88 +/- 0.19 mumol/L in Germans) than the healthy children of the same countries. In all diabetic children the plasma glutathione peroxidase activity and triglycerides were higher and the plasma HDL-cholesterols (HDLC = high density lipoprotein-cholesterol) lower than those in healthy controls. The patients showed linear correlations between blood glucose and plasma glutathione peroxidase activity, as well as in erythrocyte glutathione peroxidase activity with triglycerides (TG) and an inverse correlation with HDL-cholesterol. Plasma selenium correlated only in healthy children with triglycerides, cholesterol and HDL-cholesterol. Irrespective of the geographical region diabetics had a higher selenium status than healthy children. In addition, we found correlations between selenium and lipoproteins in the reference group. The mode of glycation, oxidative procedures and the selenium binding to lipoproteins could explain the different associations in the healthy and diabetic children.

Adolescent↗
PubMed1990

Studies on the efficacy of lipoate and dihydrolipoate in the alteration of cadmium2+ toxicity in isolated hepatocytes.

Lipoate (thioctic acid) is presently used in therapy of a variety of diseases such as liver and neurological disorders. However, nothing is known about the efficacy of lipoate and its reduced form dihydrolipoate in acute cadmium (Cd2+) toxicity which involves severe liver disturbances. Therefore, we investigated the effects of these redox compounds on Cd2(+)-induced injuries in isolated rat hepatocytes. The cells were coincubated with 150 microM Cd2+ and either 1.5-6.0 mM lipoate or 17-89 microM dihydrolipoate for up to 90 min and Cd2+ uptake as well as viability criteria were monitored. Both exposure regimens diminished Cd2+ uptake in correspondence to time and concentration. They also ameliorated Cd2(+)-induced cell deterioration as reflected by the decrease in Cd2(+)-induced membrane damage (leakage of aspartate aminotransferase), by the lessening of the Cd2(+)-stimulated lipid peroxidation (TBA-reactants) and by the increase in Cd2(+)-depleted cellular glutathione (GSH + 2 GSSG). Half-maximal protection was achieved at molar ratios of 9.9 to 19 (lipoate vs. Cd2+) and 0.25 to 0.74 (dihydrolipoate vs. Cd2+), indicating a 19.5 to 50.6 lower protective efficacy of lipoate as compared to dihydrolipoate. Lipoate induced an increase in extracellular acid-soluble thiols different from glutathione. It is suggested that dihydrolipoate primarily protects cells by extracellular chelation of Cd2+, whereas intracellular reduction of lipoate to the dihydro-compound followed by complexation of both intra- and extracellular Cd2+ contributes to the amelioration provided by lipoate.

Animals↗
PubMed1989

Selenium status in Sudanese children with protein-calorie malnutrition.

In 68 Sudanese children with severe protein-energy malnutrition, age 1-4 years, the selenium status was investigated and the results were compared with those of healthy Sudanese and German children. The median selenium content in plasma of healthy Sudanese children (x = 59 micrograms/L) and with those of marasmus (x = 57 micrograms/L) were found to be in the same range. It was lower than in healthy German children (x = 82 micrograms/L). Patients with marasmic kwashiorkor exhibited still lower values (x = 42 micrograms/L. Within each group of malnourished children (marasmus, marasmic kwashiorkor, kwashiorkor) there were patients with low and with "normal" selenium values (taking the values of healthy German children as normal). Hair selenium values were not different between marasmic Sudanese children and healthy German children, probably due to reduced hair growth in malnourished children. Plasma glutathione peroxidase activity was reduced concomitantly with plasma selenium in the patients with protein-calorie malnutrition. There was a good correlation between plasma selenium and plasma glutathione peroxidase activity. A follow-up study showed that plasma selenium decreased during rehabilitation in those patients who had a "normal" value before treatment. This is probably due to the low selenium content of the two dietary formulae used, which contained 18 and 25 micrograms/L Se of formula,. It remains questionable whether the low selenium states and low selenium intake exhibit a healthy risk inhibiting further rehabilitation of the patients with severe protein-calorie malnutrition.

Child, Preschool↗
PubMed1987

Acute selenium poisoning of a 2-year-old child.

After ingestion of an unknown amount of a gun blueing compound containing selenious acid (11 ml from the bottle fluid were missing, equivalent to 2.9 g Se) a 2-year-old girl suffered from continuous hyper-salivation, vomiting, diarrhoea, restlessness and muscle spasm. Blood pressure and pulse rate were increased. Symptomatic treatment was performed by parenteral fluid administration. The plasma Se concentration was increased to 20 times normal 5 h after ingestion. Erythrocyte Se exceeded plasma Se, 24 h after intoxication. Urinary Se excretion decreased parallel to the plasma Se concentration. Ten weeks later, the Se content of hair had risen to 10 times normal. The plasma glutathione peroxidase activity showed only a slight increase during the first 36 h, erythrocyte glutathione peroxidase, catalase and superoxide dismutase activities were not significantly altered. The child fully recovered.

Child, Preschool↗
PubMed1987

[Significance of an angiogenic factor (in omental lipid) for the vascularization of the cornea].

The existence of an angiogenic factor in the omental lipid was verified by injecting four different test materials in dosages of 50 microliters into the corneas of New Zealand rabbits. The test substances were: 1) phosphate-buffered saline solution; 2) chloroform-methanol solution; 3) phosphate-buffered saline homogenate of the chloroform-methanol extract of the lipid cake from the rabbit omentum. The experimental results show that the modes of neovascularization after injection of lipid and nonlipid materials into rabbit corneas are very similar. For angiogenesis to be stimulated, the noxious substances must be retained in the cornea for several days. One day after injection the phosphate-buffered saline solution is totally resorbed. The other test substances (2-4), are retained within the cornea for days or weeks. Test substance 1 does not induce any corneal vascularization. The injection of test substances 2-4 causes similar corneal neovascularization: the proliferation of vessels always starts from that segment of the limbus closest to the stimulation. Since the extent of vascularization after injection of chloroform-methanol solution alone is similar to that which occurs after injection of an omental lipid extract, the hypothesis of a specific angiogenic factor is not supported. Fluorescein angiography reveals a large outflow of fluid (leakage) out of the neovascularization.

Angiogenesis Inducing Agents↗