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Biomedical subjects

E Deutsch

Publications and source records attributed to E Deutsch.

At least 37 records · Page 2Linked to original sources
PubMed2000

Decreased DNA-PK activity in human cancer cells exhibiting hypersensitivity to low-dose irradiation.

Low-dose hyper-radiosensitivity (HRS) (below 0.5 Gy) has been extensively documented in the past few years. The molecular basis of this phenomenon remains largely unknown and the purpose of this study was to investigate the possible implication of the DNA repair DNA-PK complex. The activity of the DNA-PK complex, i.e. Ku DNA-end binding activity and kinase activity of the whole complex, was studied in 10 human cancer cell lines, 2 h after 0.2, 0.5 and 1 Gy irradiation. After low-dose irradiation (0.2 Gy), a marked decrease in DNA-PK activity was found in all six cell lines exhibiting HRS, whereas the DNA-PK activity was increased in the four cell lines which did not exhibit HRS. This modulation of DNA-PK activity was a rapid phenomenon occurring within the 2 h following low-dose radiation exposure. These data strongly suggest the implication of the DNA-PK repair complex in the HRS phenomenon.

Amino Acid Sequence↗
PubMed2000

Current and potential therapeutic uses of lanthanide radioisotopes.

In the last 25 years, diagnostic nuclear medicine has come to depend on the versatile chemistry of a single radioisotope, technetium-99m (Tc-99m). Different chelating molecules can be used to guide Tc-99m through various physiological pathways in the body to gain information about disease states. No single radioisotope similarly dominates therapeutic applications. In the field of radioisotope therapy, much discussion and debate have focused on what radioisotope might be "ideal" for treatment of malignant tumors. The ideal may not be a single radioisotope, but rather the class of very closely related radiolanthanides and lanthanide-like radioisotopes. These radioisotopes possess strikingly similar chemistries and thus all may be conjugated to biomolecules using a single chelate, the DOTA moiety (and its chemical analogs). They also provide a wide range of physical characteristics, such as half-lives and beta energies, that can be chosen to match the biological properties of the conjugated biomolecule and the malignant tumor. Thus, the radiolanthanide-DOTA bioconjugate model provides a set of physically diverse, but chemically very similar, therapeutic radiopharmaceutical agents, the individual members of which can be tailored to treat specific types of cancers.

Alpha Particles↗
PubMed2000

Pott's puffy tumor treated by endoscopic frontal sinusotomy.

Pott's puffy tumor is a serious extracranial complication of frontal sinusitis. The formation of this entity is facilitated by the close anatomic relationship between the paranasal sinuses and the frontal bone. Furthermore, the rich diploic venous drainage of the region enhances the spread of the infection. We report on successful functional endoscopic frontal sinusotomy in a series of four cases of Pott's puffy tumor following acute frontal sinusitis, between the years 1994 and 1997. We emphasize the advantages of this approach over the external approaches as follows: the technique treats the causative source of the disease, the morbidity is low, and it avoids facial cosmetic trauma and sequela.

Abscess↗
PubMed1999

Effectiveness of aspirin and clopidogrel combination therapy in coronary stenting.

Two hundred fifty consecutive patients underwent coronary stenting and received a 2-week course of clopidogrel (75 mg orally each day after a loading dose of 150 mg) and aspirin. There was 1 (0.4%) in-hospital death, 1 (0.4%) acute stent thrombosis, and 2 (0.8%) subacute stent thromboses. There were no Q-wave myocardial infarctions, vascular complications, or repeat interventions at 30-day follow-up.

Aged↗
PubMed1999

DnrD cyclase involved in the biosynthesis of doxorubicin: purification and characterization of the recombinant enzyme.

Mutations in the Streptomyces peucetius dnrD gene block the ring cyclization leading from aklanonic acid methyl ester (AAME) to aklaviketone (AK), an intermediate in the biosynthetic pathway to daunorubicin (DNR) and doxorubicin. To investigate the role of DnrD in this transformation, its gene was overexpressed in Escherichia coli and the DnrD protein was purified to homogeneity and characterized. The enzyme was shown to catalyze the conversion of AAME to AK presumably via an intramolecular aldol condensation mechanism. In contrast to the analogous intramolecular aldol cyclization catalyzed by the TcmI protein from the tetracenomycin (TCM) C pathway in Streptomyces glaucescens, where a tricyclic anthraquinol carboxylic acid is converted to its fully aromatic tetracyclic form, the conversion catalyzed by DnrD occurs after anthraquinone formation and requires activation of a carboxylic acid group by esterification of aklanonic acid, the AAME precursor. Also, the cyclization is not coupled with a subsequent dehydration step that would result in an aromatic ring. As the substrates for the DnrD and TcmI enzymes are among the earliest isolable intermediates of aromatic polyketide biosynthesis, an understanding of the mechanism and active site topology of these proteins will allow one to determine the substrate and mechanistic parameters that are important for aromatic ring formation. In the future, these parameters may be able to be applied to some of the earlier polyketide cyclization processes that currently are difficult to study in vitro.

Base Sequence↗
PubMed1999

Novel distal occluder washout method for prevention of no-reflow during stenting of saphenous vein grafts.

This study assessed safety of the distal occlusion washout (DOW) method for prevention of no-reflow during stenting of degenerated saphenous vein grafts (SVGs). The DOW method involves protection of distal native coronary circulation with an occlusive balloon during the pretreatment and washout steps prior to stenting. Outcomes of stenting of 23 grafts in 21 patients after pretreatment with the DOW method were evaluated. The mean graft age was 7.4 +/- 4.3 years. The mean treated lesion length was 53 +/- 28 mm. Total occlusions were treated in 6 grafts and thrombotic lesions in 10 nontotally occluded grafts. One non-Q-wave MI and one acute stent thrombosis were observed. No deaths, Q-wave MIs, or subacute thromboses occurred. Follow-up in 18/21 (85.7%) patients at 28 +/- 8 weeks demonstrated target graft revascularization in 1 (5%) patient. The DOW method prevented clinically significant no-reflow in all 23 degenerated SVGs stented.

Aged↗
PubMed1999

The expression of TGF-beta receptors in human atherosclerosis: evidence for acquired resistance to apoptosis due to receptor imbalance.

The degree of cellularity in vascular lesions is determined by the balance between the migration and proliferation of cells relative to their rate of egress and apoptosis. Transforming growth factor-beta(1) can act as a potent antiproliferative and apoptotic factor for proliferating vascular cells. Our laboratory has previously identified cells cultured from human vascular lesions that are resistant to the antiproliferative effect of TGF-beta(1) due to an acquired mutation in the Type II receptor for TGF-beta(1). In the present studies, the expression of the Type I and II receptors in coronary and carotid atherosclerotic lesions was analysed by immunostaining, RT-PCR, and in situ RT-PCR. Levels of the Type I and Type II receptors varied widely within lesions, with the highest levels in the fibrous cap and at discrete foci within the lesion. Regions of smooth muscle-like cells (SMC) were commonly found that were Type I positive but Type II receptor negative. In 43 cell lines cultured from 126 human lesions, 84% of the lesion-derived cell (LDC) cultures exhibited functional resistance to the antiproliferative effect of TGF-beta(1). This resistance was conferred against TGF-beta(1), TGF-beta(2), and TGF- beta(3), but not interferon-gamma or mimosine. While normal SMC exhibited a four-fold increase in the rate of apoptosis after TGF- beta(1) treatment, most LDC were resistant to apoptosis in response to TGF-beta(1). Resistant cells exhibited selective loss of Type II receptor expression, and retroviral transfection of Type II receptor cDNA partially corrected the functional deficit. Thus, resistance to apoptosis may lead to the slow proliferation of resistant cell subsets, thereby contributing to the progression of atherosclerotic and restenotic lesions.

Activin Receptors, Type I↗
PubMed1999

99mTc(L-L)3+ complexes containing ether analogs of DMPE.

Novel 99mTc(L-L)3+ complexes have been investigated for potential use in myocardial perfusion imaging. Bidentate chelators have been prepared that are based on substituent analogs of 1,2-bis(dimethylphosphino)ethane, onto which alkyl ether groups have been incorporated. The new ligands are: (1) MMPE, 1,2-bis(methyl methoxyethyl phosphino)ethane, (2) MIBPE, 1,2-bis(methyl methoxyisobutyl phosphino)ethane, (3) FURPE, 1,2-bis(methyl tetrahydrofuran phosphino)ethane, and (4) PYRPE, 1,2-bis(methyl tetrahydropyran phosphino)ethane. These ligands have been reacted with 99mTc and the resulting complexes evaluated for myocardial imaging properties. 99mTc(MMPE)3+ exhibited the most favorable myocardial imaging characteristics in animal models. Results indicate that pendent ether moieties can improve the myocardial imaging properties of cationic technetium complexes.

Animals↗
PubMed1999

Preparation and characterization of technetium complexes with Schiff base and phosphine coordination. 1. Complexes of technetium-99g and -99m with substituted acac2en and trialkyl phosphines (where acac2en = N,N'-ethylenebis[acetylacetone iminato]).

A series of 23 technetium(III) complexes of the type [TcL(PR3)2]+, where L represents a tetradentate Schiff base ligand in the equatorial plane and PR3 represents the axial phosphine ligands, are reported. Full ligand syntheses and characterizations are included. The technetium complexes were prepared with 99mTc to study the organ distribution in guinea pigs at 5 and 60 min postinjection. Four prototypical complexes of the series were also prepared with either 99gTc or 99gTc/99mTc (designated as carrier-added) to allow macroscopic characterization. Equivalence of the 99gTc and 99mTc complexes was demonstrated by dual detection high performance liquid chromatography (HPLC) techniques. The development of a one-step preparation from the standard two-step method is discussed for some complexes. Biodistribution data are related to structure and lipophilicity. None of the complexes in the series exhibited a tendency for in vivo reduction. Myocardial uptake was favorable for a number of complexes. The optimal agent from this series for further imaging development was chosen based on myocardial uptake, rapid blood and liver clearance, and ability to be formulated as a one-step kit.

Animals↗
PubMed1999

The emerging role of low-molecular-weight heparin and antiplatelet therapies in the cardiac catheterization laboratory.

The advent of new pharmacotherapies and interventional devices has exponentially increased the breadth of coronary procedures in a variety of clinical settings. The low-molecular-weight heparins, a new class of antithrombins, offer several advantages over unfractionated heparin as anticoagulants. New antiplatelet agents have also been developed that block components of the platelet aggregation pathway not inhibited by aspirin. The use of these new therapies has the potential to significantly improve the outcome of percutaneous coronary interventions. One low-molecular-weight heparin, enoxaparin, was shown in the ESSENCE trial to be significantly superior to unfractionated heparin in the medical management of unstable angina. Evidence from ESSENCE suggests that enoxaparin used in conjunction with percutaneous revascularization and stenting does not cause increased bleeding. Trials directly comparing the safety and efficacy of heparin and enoxaparin as adjunctive therapies in percutaneous interventions are in progress. In addition, intramural delivery of enoxaparin to achieve a locally high concentration is being investigated for the prevention of restenosis after coronary stenting. Aspirin together with ticlopidine, which inhibits adenosine diphosphate-induced platelet activation, has been shown to be superior to aspirin plus anticoagulation in trials of patients undergoing percutaneous revascularization with stenting. Clopidogrel has emerged as a possible alternative to ticlopidine. Antiplatelet therapies directed against the glycoprotein IIb/IIIa receptor, which plays a critical role in aggregation, have been tested in several clinical trials in patients undergoing percutaneous intervention. The combination of new antiplatelet and new anticoagulant therapies may offer added benefit not seen with the individual agents alone. The safety and effectiveness of such new regimens is currently being investigated in a number of clinical trials.

Anticoagulants↗
PubMed1999

Office-based insertion of pressure equalization tubes: the role of laser-assisted tympanic membrane fenestration.

OBJECTIVE: To describe the role of the hand-held otoscope combined with a flashscanner CO2 laser, OtoLAM (ESC/Sharplan, Yokneam, Israel), for pressure equalization tube (PET) insertion in an office setting. STUDY DESIGN: Prospective, multisite, clinical cohort trial (Institutional Review Board approved; informed consent) in the setting of pediatric otolaryngology outpatient departments at four tertiary care children's hospitals. METHODS: Selected for the study were 54 patients (96 ears), ages 6 months to 23 years, who met standard indications for PET insertion using cold-knife myringotomy and tube insertion under general anesthesia. PETs were indicated for recurrent otitis media, chronic otitis media with effusion, and eustachian tube dysfunction-all unresponsive to medical therapy. Topical anesthesia was achieved with iontophoresis (n = 1) or topical anesthesia: 8% tetracaine on an Otowick (Xomed Surgical Products, Jacksonville, FL, catalogue No. 400141) against the tympanic membrane for 45 to 180 minutes (n = 53). Laser-assisted tympanic membrane fenestration was performed with the OtoLAM set at single pulse, 2.0- to 2.6-mm spot size, and between 3 and 18 W. Insertion of grommets was accomplished using the otomicroscope and an "alligator" microforceps. Restraints with papoose were used in 79% of children with a mean age of 34.4 months (SD = 60.9 mo). Clinical, parent/patient, and physician satisfaction and comparative cost impact outcomes are described. RESULTS: All ears but three (3%) underwent successful placement of a PET. Pain was described as "absent" in 39%, "present but tolerable" in 30%, and "severe" in 30% of children at the time of procedure; 5 minutes after the procedure pain was described as "absent" in 75%, "present but tolerable" in 22%, and "severe" in 3%. Tube plugging (3 of 74 available ears; 4%) or persistent otorrhea (1 of 74 ears; 1.4%) occurred infrequently at the 1-month follow-up. Before PET insertion, hearing loss was noted in 66% of cases (mild, 38%; moderate, 22%; and severe, 6%). Mild hearing loss was noted in only 8% and moderate hearing loss in 2% of 47 (50%) of the ears at the 3-month follow-up. Ninety-two percent of parents were highly satisfied with the procedure in preference to PETs in the operating room under general anesthesia, and 97% preferred OtoLAM with PET insertion, rather than further courses of antibiotics; only one parent would rather have had the PET insertion under general anesthesia. Cost savings to health care organizations, particularly payers, and to parents are substantial (32%-48%) and warrant attention. Cost to the physician is manageable only if an appropriate approach to the third party payers results in a substantial increase in reimbursements. CONCLUSIONS: The data indicate excellent clinical effectiveness, reduced risk, and high parent and physician satisfaction. Strong incentives for physicians to use this technique are in all stakeholders' best interests. These incentives need to evolve as soon as possible for the more widespread acceptance of OtoLAM with PET insertion in an office setting for appropriately selected patients.

Adolescent↗
PubMed1999

Glucocorticoid resistance caused by reduced expression of the glucocorticoid receptor in cells from human vascular lesions.

Mechanisms that control the balance between cell proliferation and death are important in the development of vascular lesions. Rat primary smooth muscle cells were 80% inhibited by low microgram doses of hydrocortisone (HC) and 50% inhibited by nanogram concentrations of transforming growth factor-beta1 (TGF-beta1), although some lines acquired resistance in late passage. However, comparable doses of HC, or TGF-beta1, failed to inhibit most human lesion-derived cell (LDC) lines. In sensitive LDC, HC (10 microg/mL) inhibited proliferation by up to 50%, with obvious apoptosis in some lines, and TGF-beta1 inhibited proliferation by more than 90%. Collagen production, as measured by [3H]proline incorporation or RIA for type III pro-collagen, was either unaffected or increased in the LDCs by HC. These divergent responses between LDC lines were partially explained by the absence of the glucocorticoid receptor (GR) and heat shock protein 90 mRNA in 10 of 12 LDC lines, but the presence of the mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type II. Western blot analysis confirmed the absence of the GR protein in cells lacking GR mRNA. Immunohistochemistry of human carotid lesions showed high levels of GR in the tunica media, but large areas lacking GR in the fibrous lesion. Considering the absence of the GR in most lines, the effects of HC may be elicited through the mineralocorticoid receptor. Functional resistance to the antiproliferative and antifibrotic effects of HC may contribute to excessive wound repair in atherosclerosis and restenosis.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

The protection of the person in medical research in Germany.

Because of its history Germany has many rules concerning the protection of persons in medical research. In fact Germany was the first state to issue a directive regulating medical experimentation with human beings in the year 1900. The ten principles of Nuremberg originated out of the medical case. Germany adheres to the Revised Declaration of Helsinki of the World Medical Association and will probably sign the European convention on biomedicine. The pharmaceutical act contains elaborate provisions for the protection of the patient or proband, e.g. informed consent, risk-benefit ratio, no experimentation on prisoners, approval of a local ethics committee. Moreover in pharmaceutical trials there has to be third party accident insurance for the experimental subject. There is no strict liability for medical experimentation, but the standard of care is high. In general the German law seems to be adequate for the protection of experimental subjects.

Confidentiality↗
PubMed1999

[Medical confidentiality and data protection in medical research-- legal aspects].

Medical confidentiality and data protection are important for medical research. They should not impede medical progress. Unfortunately, the German legal situation is not easy to understand. There are different statutes which have to be reconciled. It is necessary that by special statute the particular problems of medical research and confidentiality as well as data protection should be regulated.

Confidentiality↗
PubMed1998

Spontaneous spinal epidural hematoma with spinal cord compression complicating plasma cell myeloma. A case report.

STUDY DESIGN: A case is reported in which a patient had acute paraplegia with sensory loss caused by a spontaneous epidural hematoma that was ascribed to bleeding of pre-existing myeloma lesions of the thoracic vertebrae. OBJECTIVES: To highlight the causes of secondary epidural hematomas with special attention to pre-existing vertebral or epidural lesions. SUMMARY OF BACKGROUND DATA: There are no apparent previous reports of epidural spinal hematomas ascribed to underlying malignant diseases. Benign dysplasia, such as hemangioma or Paget's disease, has been implicated in a few cases. METHODS: A case of spontaneous dorsal epidural hematoma is reported in a patient followed up for plasma cell myeloma with osteolytic lesions in the lower thoracic spine. There was no history of major trauma or coagulation disorders. Complete loss of motor and sensory function in both lower limbs was noted, with sphincter dysfunction. Magnetic resonance imaging of the thoracic spine showed a large posterolateral epidural hematoma responsible for spinal cord compression. RESULTS: The patient failed to improve despite surgical decompression within 6 hours of symptom onset. He died 13 days later of refractory bacterial pneumonia. A large epidural hematoma adjacent to myelomatous lesions of the thoracic vertebrae was found at autopsy. CONCLUSIONS: This is the first reported case of spontaneous epidural hematoma ascribed to underlying malignant disease, with confirmation of the diagnosis by postmortem examination. Possible mechanisms include tumor-related epidural inflammation and fragility of epidural venous plexuses.

Aged↗
PubMed1998

[Workshop "Radio-oncology and the Law"].

From 25 to 27 Sept 1997, a workshop was organized at the Essen Medical School (Universitätsklinikum Essen), at which radiooncologists and jurists from universities and courts as well as lawyers contributed their views on mutual problems. The following topics were discussed by papers and in round table meetings: "Requirements on the patient's information", "definition of therapeutic guidelines-limits of clinical research and standard treatments", "treatment documentation", "liability of the physician for treatment faults" and "technical standard and preserve of quality". The consensual guidelines to the topics "patient's information", "therapeutic guidelines" and "liability" are presented here.

Documentation↗
PubMed1998

Cytokine evaluation in throat infections.

Inflammatory cytokines have been shown to play an important role in the pathogenesis of various inflammatory processes. In throat infections, intracellular inflammatory cytokines have been detected from the sites of inflammation. The present study aimed to evaluate serum cytokine levels of patients with throat infections and correlate them to the inflammatory parameters and type of inflammation. Significantly higher inflammatory cytokine levels (interleukin [IL]-6 > 7 pg/mL, IL-1 > 1 beta pg/mL, tumor necrosis factor alpha > 1 pg/mL) were detected in most of the patients as opposed to healthy controls. Clinical parameters of infection (fever > 38 degrees C, leukocytosis > 11,000 white blood cells per cubic millimeter, polymorphonuclear neutrophils > 75%) were significantly correlated with high levels of inflammatory cytokines: mainly IL-6 and tumor necrosis factor alpha, and to a lesser degree with IL-1 beta. No correlation, however, was found between the type of inflammation and cytokine levels. The present study indicates a role of inflammatory cytokines in the pathogenesis of throat infections and the need for an anti-inflammatory and anticytokine therapeutic approach.

Adolescent↗