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1.
Colloids Surf B Biointerfaces ; 108: 103-9, 2013 Aug 01.
Article in English | MEDLINE | ID: mdl-23524083

ABSTRACT

Textile-based drug delivery systems have a high potential for innovative medical and gerontechnological applications. In this study, the tribological behaviour and lubrication properties of a novel textile with drug delivery function/finishing was investigated by means of friction experiments that simulated cyclic dynamic contacts with skin under dry and wet conditions. The textile drug delivery system is based on a loadable biopolymer dressing on a polyester (PES) woven fabric. The fabrics were finished with low (LC) and highly cross-linked (HC) polysaccharide dressings and investigated in the unloaded condition as well as loaded with phytotherapeutic substances. The mechanical resistance and possible abrasion of the functional coatings on the textile substrate were assessed by friction measurements and scanning electron microscopical analyses. Under dry contact conditions, all investigated fabrics (PES substrate alone and textiles with loaded and unloaded dressings) showed generally low friction coefficients (0.20-0.26). Under wet conditions, the measured friction coefficients were typically higher (0.34-0.51) by a factor of 1.5-2. In the wet condition, both loaded drug delivery textiles exhibited 7-29% lower friction (0.34-0.41) than the PES fabric with unloaded dressings (0.42-0.51), indicating pronounced lubrication effects. The lubrication effects as well as the abrasion resistance of the studied textiles with drug delivery function depended on the degree of dilution of the phytotherapeutic substances. Lubricating formulations of textile-based drug delivery systems which reduce friction against the skin might be promising candidates for advanced medical textile finishes in connection with skin care and wound (decubitus ulcer) prevention.


Subject(s)
Drug Carriers/chemistry , Linoleic Acids/chemistry , Lubricants/chemistry , Plant Oils/chemistry , Polyesters/chemistry , Polysaccharides/chemistry , gamma-Linolenic Acid/chemistry , Friction , Humans , Microscopy, Electron, Scanning , Oenothera biennis , Skin Care , Surface Properties , Textiles
2.
J Biomed Mater Res A ; 101(3): 827-41, 2013 Mar.
Article in English | MEDLINE | ID: mdl-22968899

ABSTRACT

In this study, the in vivo recellularization and neovascularization of nanosized bioactive glass (n-BG)-coated decellularized trabecular bone scaffolds were studied in a rat model and quantified using stereological analyses. Based on the highest amount of vascular endothelial growth factor (VEGF) secreted by human fibroblasts grown on n-BG coatings (0-1.245 mg/cm(2)), decellularized trabecular bone samples (porosity: 43-81%) were coated with n-BG particles. Grown on n-BG particles at a coating density of 0.263 mg/cm(2), human fibroblasts produced 4.3 times more VEGF than on uncoated controls. After 8 weeks of implantation in Sprague-Dawley rats, both uncoated and n-BG-coated samples were well infiltrated with newly formed tissue (47-48%) and blood vessels (3-4%). No significant differences were found in cellularization and vascularization between uncoated bone scaffolds and n-BG-coated scaffolds. This finding indicates that the decellularized bone itself may exhibit growth-promoting properties induced by the highly interconnected pore microarchitecture and/or proteins left behind on decellularized scaffolds. Even if we did not find proangiogenic effects in n-BG-coated bone scaffolds, a bioactive coating is considered to be beneficial to impart osteoinductive and osteoconductive properties to decellularized bone. n-BG-coated bone grafts have thus high clinical potential for the regeneration of complex tissue defects given their ability for recellularization and neovascularization.


Subject(s)
Bone Regeneration , Bone Substitutes/chemistry , Coated Materials, Biocompatible/chemistry , Femur/chemistry , Glass/chemistry , Neovascularization, Physiologic , Tissue Scaffolds/chemistry , Animals , Fibroblasts/cytology , Fibroblasts/metabolism , Humans , Materials Testing , Rats , Rats, Sprague-Dawley , Swine , Vascular Endothelial Growth Factor A/metabolism
3.
J Mech Behav Biomed Mater ; 14: 199-207, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23032327

ABSTRACT

Skin is a multilayer composite and exhibits highly non-linear, viscoelastic, anisotropic material properties. In many consumer product and medical applications (e.g. during shaving, needle insertion, patient re-positioning), large tissue displacements and deformations are involved; consequently large local strains in the skin tissue can occur. Here, we present a novel imaging-based method to study skin deformations and the mechanics of interacting skin layers of full-thickness skin. Shear experiments and real-time video recording were combined with digital image correlation and strain field analysis to visualise and quantify skin layer deformations during dynamic mechanical testing. A global shear strain of 10% was applied to airbrush-patterned porcine skin (thickness: 1.2-1.6mm) using a rotational rheometer. The recordings were analysed with ARAMIS image correlation software, and local skin displacement, strain and stiffness profiles through the skin layers determined. The results of this pilot study revealed inhomogeneous skin deformation, characterised by a gradual transition from a low (2.0-5.0%; epidermis) to high (10-22%; dermis) shear strain regime. Shear moduli ranged from 20 to 130kPa. The herein presented method will be used for more extended studies on viable human skin, and is considered a valuable foundation for further development of constitutive models which can be used in advanced finite element analyses of skin.


Subject(s)
Mechanical Phenomena , Molecular Imaging/methods , Skin , Animals , Biomechanical Phenomena , Humans , Image Processing, Computer-Assisted , Molecular Imaging/instrumentation , Stress, Mechanical , Swine , Time Factors , Uncertainty , Video Recording
4.
Gerontology ; 58(6): 513-7, 2012.
Article in English | MEDLINE | ID: mdl-22487874

ABSTRACT

BACKGROUND: Skin aging is a risk factor for a decubitus and biophysical skin properties could help to identify persons at risk. Whether such biophysical properties of aged human skin differ between areas is undetermined. OBJECTIVE: To investigate whether viscoelasticity, hydration or friction differ between important areas for decubitus risk. METHODS: Pilot study in 32 (18 female, 14 male) acute and subacute old patients aged 81.9 ± 5.9 years (±SD), without active skin disease after an average of 10 days of stay. Assessment of skin resilience/viscoelasticity (E) and hydration (H) at the volar forearm (VF), trochanter (TR) and the sacrum (SA), nutrition by a Mini Nutritional Assessment (MNA), total body water (TBW), lean body mass (LBM), % body fat (%F) by bioimpedance and routine laboratory parameters (hemoglobin, hematocrit, leukocytes, C-reactive protein, serum proteins and creatinine). RESULTS: Mean body mass index (27 ± 4.2), MNA (22.5 ± 2.9), Braden score (20 ± 2.5), E (68.5 ± 6.0%) and H (38.3 ± 6.7) at any site and laboratory parameters did not differ by sex. Men had more TBW (+12 ± 1.5 liters), LBM (+9 ± 2 kg), less %F (-8.8 ± 2.1%), increased H-TR (+7.11 ± 2.8) and H-SA (+5.68 ± 2.5). Overall E-VF correlated significantly with E-TR (r(2) = 0.40, p < 0.0001) and E-SA (r(2) = 0.40, p < 0.0001). In contrast, skin hydration was not correlated. CONCLUSION: Results of forearm elasticity experiments can be used as a model for other body sites at risk for the development of pressure ulcers.


Subject(s)
Aging/physiology , Skin Aging/physiology , Aged , Aged, 80 and over , Biomechanical Phenomena/physiology , Biophysical Phenomena , Body Composition , Body Water/metabolism , Elasticity , Female , Humans , Male , Nutrition Assessment , Pilot Projects , Pressure Ulcer/etiology , Pressure Ulcer/physiopathology , Risk Factors , Viscosity
5.
Skin Res Technol ; 15(3): 288-98, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19624425

ABSTRACT

BACKGROUND/PURPOSE: The mechanical properties of human skin are known to change with ageing, rendering skin less resistant to friction and shear forces, as well as more vulnerable to wounds. Until now, only few and contradictory results on the age-dependent friction properties of skin have been reported. This study has investigated in detail the influence of age on the friction of human skin against textiles. METHODS: In vivo skin-friction measurements on a force plate were combined with skin analyses concerning elasticity, hydration, pH value and sebum content. Thirty-two young and 28 aged persons rubbed their volar forearm in a reciprocating motion against various textiles on the force plate, using defined normal loads and sliding velocities, representing clinically relevant contact conditions. RESULTS: Mean friction coefficients ranged from 0.30 +/- 0.04 (polytetrafluoroethylene) to 0.43 +/- 0.04 (cotton/polyester). No significant differences in the friction properties of skin were found between the age groups despite skin elasticity being significantly lower in the aged persons. Skin hydration was significantly higher in the elderly, whereas no significant differences were observed in either skin pH value or sebum content. CONCLUSION: Adhesion is usually assumed to be the dominant factor in skin friction, but our observations imply that deformation is also an important factor in the friction of aged skin. In the elderly, lower skin elasticity and skin turgor are associated with more pronounced skin tissue displacements and greater shear forces during frictional contact, emphasizing the importance of friction reduction in wound-prevention programmes.


Subject(s)
Aging/physiology , Clothing , Skin Physiological Phenomena , Skin Tests/methods , Textiles , Adolescent , Adult , Aged , Aged, 80 and over , Elastic Modulus/physiology , Female , Friction , Humans , Male , Middle Aged , Surface Properties , Young Adult
6.
J R Soc Interface ; 5(28): 1317-28, 2008 Nov 06.
Article in English | MEDLINE | ID: mdl-18331977

ABSTRACT

Friction and shear forces, as well as moisture between the human skin and textiles are critical factors in the formation of skin injuries such as blisters, abrasions and decubitus. This study investigated how epidermal hydration affects the friction between skin and textiles.The friction between the inner forearm and a hospital fabric was measured in the natural skin condition and in different hydration states using a force plate. Eleven males and eleven females rubbed their forearm against the textile on the force plate using defined normal loads and friction movements. Skin hydration and viscoelasticity were assessed by corneometry and the suction chamber method, respectively.In each individual, a highly positive linear correlation was found between skin moisture and friction coefficient (COF). No correlation was observed between moisture and elasticity, as well as between elasticity and friction. Skin viscoelasticity was comparable for women and men. The friction of female skin showed significantly higher moisture sensitivity. COFs increased typically by 43% (women) and 26% (men) when skin hydration varied between very dry and normally moist skin. The COFs between skin and completely wet fabric were more than twofold higher than the values for natural skin rubbed on a dry textile surface.Increasing skin hydration seems to cause gender-specific changes in the mechanical properties and/or surface topography of human skin, leading to skin softening and increased real contact area and adhesion.


Subject(s)
Body Water/physiology , Friction , Skin Physiological Phenomena , Textiles , Adult , Biomechanical Phenomena , Female , Humans , Male , Sex Factors
7.
Skin Res Technol ; 14(1): 77-88, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18211605

ABSTRACT

BACKGROUND/PURPOSE: Prolonged pressure as well as friction and shear forces at the skin-textile interface are decisive physical parameters in the development of decubitus. The present article describes the contact phenomena at the skin-textile interface and the development of a purpose-built textile friction analyser (TFA) for the tribological assessment of skin-fabric interactions, in connection with decubitus prevention. METHODS: Interface pressure distributions were recorded in the pelvic and femoral regions between supine persons and a foam mattress. Fabrics made of various natural and synthetic yarns were investigated using the TFA. A vertical load of 7.7 kPa was applied to the swatches, simulating high interface pressures at the skin-fabric interface and clinical conditions of bedridden persons. Fabrics were rubbed in reciprocating motions against a validated skin-simulating material to determine static as well as dynamic friction coefficients (COFs). RESULTS: Maximum contact pressures ranged from 5.2 to 7.7 kPa (39-58 mmHg) and exceeded the capillary closure pressure (32 mmHg) in all investigated bedding positions. For both COFs, a factor of 2.5 was found between the samples with the lowest and highest values. Our results were in a similar range to COFs found in measurements on human skin in vivo. The results showed that our test method can detect differences of 0.01 in friction coefficients. CONCLUSION: TFA measurements allow the objective and reliable study of the tribology of the skin-textile biointerface and will be used to develop medical textiles with improved performance and greater efficacy for decubitus prevention.


Subject(s)
Biomechanical Phenomena/methods , Friction , Materials Testing/methods , Pressure/adverse effects , Textiles/adverse effects , Adult , Animals , Biomechanical Phenomena/instrumentation , Cellulose/adverse effects , Clothing/adverse effects , Cotton Fiber , Female , Humans , Male , Models, Biological , Pelvis/physiopathology , Polyesters/adverse effects , Polytetrafluoroethylene/adverse effects , Posture , Pressure Ulcer/etiology , Pressure Ulcer/physiopathology , Pressure Ulcer/prevention & control , Skin/physiopathology , Statistics, Nonparametric , Wool/adverse effects
8.
J Neurosci Methods ; 167(1): 51-62, 2008 Jan 15.
Article in English | MEDLINE | ID: mdl-17920134

ABSTRACT

Many studies over the past two decades have shown that people can use brain signals to convey their intent to a computer through brain-computer interfaces (BCIs). These devices operate by recording signals from the brain and translating these signals into device commands. They can be used by people who are severely paralyzed to communicate without any use of muscle activity. One of the major impediments in translating this novel technology into clinical applications is the current requirement for preliminary analyses to identify the brain signal features best suited for communication. This paper introduces and validates signal detection, which does not require such analysis procedures, as a new concept in BCI signal processing. This detection concept is realized with Gaussian mixture models (GMMs) that are used to model resting brain activity so that any change in relevant brain signals can be detected. It is implemented in a package called SIGFRIED (SIGnal modeling For Real-time Identification and Event Detection). The results indicate that SIGFRIED produces results that are within the range of those achieved using a common analysis strategy that requires preliminary identification of signal features. They indicate that such laborious analysis procedures could be replaced by merely recording brain signals during rest. In summary, this paper demonstrates how SIGFRIED could be used to overcome one of the present impediments to translation of laboratory BCI demonstrations into clinically practical applications.


Subject(s)
Brain/physiology , Signal Detection, Psychological/physiology , Signal Processing, Computer-Assisted , User-Computer Interface , Adult , Algorithms , Brain Mapping , Electrocardiography/methods , Electroencephalography/methods , Humans , Male , Man-Machine Systems , Normal Distribution , Online Systems , Software Validation
9.
Herzschrittmacherther Elektrophysiol ; 18(4): 250-8, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18084799

ABSTRACT

AIMS: Bifocal right atrial pacing (BP) has been reported to increase arrhythmia-free intervals in patients with paroxysmal atrial fibrillation (PAF) under antiarrhythmic drugs. This study compares AF burden with unifocal pacing (UP) vs BP under sotalol. METHODS: In 19 patients with PAF a DDDR pacemaker with right atrial lateral and CS ostial leads was implanted. Sotalol was initiated. After a 3 month back-up pacing period patients were randomized to continuous UP or BP for 3 months and crossed over for 3 more months. Primary endpoint was AF burden. Secondary endpoints included number of episodes, time to first recurrence and safety of BP. RESULTS: The intention to treat analysis revealed 12.4% AF during back-up, 6.2% during UP and BP (p=0.91 UP vs BP, p=0.08 back-up vs UP and p=0.07 back-up vs BP). Per protocol analysis showed no advantage of either pacing mode (UP 4.8% and BP 5.4% AF, p=0.64). Overdrive pacing reduced AF burden to 6.2 vs 8.8% during back-up (p=0.09). Septal lead dislodgement occurred in 3 patients. CONCLUSION: Atrial pacing tends to reduce AF burden in patients with PAF under sotalol. An incremental effect of BP vs UP cannot be confirmed. BP may be complicated by elevated lead dislodgement rates.


Subject(s)
Anti-Arrhythmia Agents/administration & dosage , Anti-Arrhythmia Agents/blood , Atrial Fibrillation/therapy , Bradycardia/therapy , Electrodes, Implanted , Heart Atria/physiopathology , Pacemaker, Artificial , Sick Sinus Syndrome/therapy , Sotalol/administration & dosage , Sotalol/blood , Aged , Atrial Fibrillation/physiopathology , Bradycardia/physiopathology , Combined Modality Therapy , Cross-Over Studies , Electrocardiography , Female , Follow-Up Studies , Hemodynamics/physiology , Humans , Male , Middle Aged , Recurrence , Sick Sinus Syndrome/physiopathology , Single-Blind Method , Sinoatrial Node/physiopathology
10.
J Neural Eng ; 4(3): 264-75, 2007 Sep.
Article in English | MEDLINE | ID: mdl-17873429

ABSTRACT

Signals from the brain could provide a non-muscular communication and control system, a brain-computer interface (BCI), for people who are severely paralyzed. A common BCI research strategy begins by decoding kinematic parameters from brain signals recorded during actual arm movement. It has been assumed that these parameters can be derived accurately only from signals recorded by intracortical microelectrodes, but the long-term stability of such electrodes is uncertain. The present study disproves this widespread assumption by showing in humans that kinematic parameters can also be decoded from signals recorded by subdural electrodes on the cortical surface (ECoG) with an accuracy comparable to that achieved in monkey studies using intracortical microelectrodes. A new ECoG feature labeled the local motor potential (LMP) provided the most information about movement. Furthermore, features displayed cosine tuning that has previously been described only for signals recorded within the brain. These results suggest that ECoG could be a more stable and less invasive alternative to intracortical electrodes for BCI systems, and could also prove useful in studies of motor function.


Subject(s)
Algorithms , Arm/physiology , Brain Mapping/methods , Cerebral Cortex/physiology , Electroencephalography/methods , Evoked Potentials, Motor/physiology , Movement/physiology , Adult , Female , Humans , Male
11.
J Mater Sci Mater Med ; 18(7): 1287-98, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17211724

ABSTRACT

Titanium dioxide (TiO(2)) nanoparticles were investigated for bone tissue engineering applications with regard to bioactivity and particle cytotoxicity. Composite films on the basis of poly(D,L lactid acid) (PDLLA) filled with 0, 5 and 30 wt% TiO(2) nanoparticles were processed by solvent casting. Bioactivity, characterised by formation of hydroxyapatite (HA) on the materials surface, was investigated for both the free TiO(2) nanoparticles and PDLLA/TiO(2) composite films upon immersion in supersaturated simulated body fluid (1.5 SBF) for up to 3 weeks. Non-stoichiometric HA nanocrystals (ns-HA) with an average diameter of 40 nm were formed on the high content (30 wt% TiO(2)) composite films after 2 weeks of immersion in 1.5 SBF. For the pure PDLLA film and the low content composite films (5 wt% TiO(2)) trace amounts of ns-HA nanocrystals were apparent after 3 weeks. The TiO(2) nanopowder alone showed no bioactivity. The effect of TiO(2) nanoparticles (0.5-10,000 microg/mL) on MG-63 osteoblast-like cell metabolic activity was assessed by the MTT assay. TiO(2) particle concentrations of up to 100 microg/mL had no significant effect on MG-63 cell viability.


Subject(s)
Biocompatible Materials/chemistry , Bone Substitutes/chemistry , Lactic Acid/chemistry , Nanoparticles/chemistry , Osteoblasts/physiology , Polymers/chemistry , Tissue Engineering/methods , Titanium/chemistry , Body Fluids/chemistry , Cell Culture Techniques/methods , Cell Line , Cell Proliferation , Cell Survival , Humans , Materials Testing , Nanoparticles/ultrastructure , Osteoblasts/cytology , Particle Size , Polyesters
12.
J Biomed Mater Res B Appl Biomater ; 73(2): 229-37, 2005 May.
Article in English | MEDLINE | ID: mdl-15756657

ABSTRACT

This article deals with enzyme-induced biodegradation behavior of thermoplastic polyether-urethane (TPU). Porous scaffolds were processed by a new foaming method applied in hot pressing and injection molding. The scaffolds were subsequently gamma sterilized. The samples were incubated with cholesterol esterase (CE) for 28 days to simulate an enzymatic degradation order to assess polymer biostability. The main focus of degradation products was the most toxic one: methylene dianiline (MDA). LC/MS was used to separate the breakdown products and to identify possible MDA amounts. The results showed that (a) the hot-pressed sample released an MDA amount almost twice as large (0.26 ng +/- 0.008) as that of the injection-molded samples (0.15 ng +/- 0.003) after incubation with enzyme activity in the physiological range, and (b) a tenfold increase in CE activity revealed considerably higher MDA amounts (7540.0 ng +/- 0.004). This enzyme concentration is physiologically unlikely, however, but may occur for extreme high inflammation behavior. Even for extremely high levels of CE enzyme, the scaffold will not discharge MDA above toxic levels. The injection-molded samples sterilized at 25 kGy seem to represent the most promising processing method. Therefore, the new injection-molding foaming process of polyether-urethane can be considered appropriate for use as a biomaterial.


Subject(s)
Biocompatible Materials/radiation effects , Cholesterol Oxidase/metabolism , Gamma Rays , Polyurethanes/pharmacokinetics , Polyurethanes/radiation effects , Animals , Biocompatible Materials/pharmacokinetics , Biodegradation, Environmental , Cattle , Dose-Response Relationship, Radiation , Drug Stability , Kinetics , Mass Spectrometry , Pancreas/enzymology , Polyurethanes/toxicity , Spectroscopy, Fourier Transform Infrared , Thermodynamics
13.
Phys Rev Lett ; 92(7): 071102, 2004 Feb 20.
Article in English | MEDLINE | ID: mdl-14995836

ABSTRACT

We present the results of a search for point sources of high-energy neutrinos in the northern hemisphere using AMANDA-II data collected in the year 2000. Included are flux limits on several active-galactic-nuclei blazars, microquasars, magnetars, and other candidate neutrino sources. A search for excesses above a random background of cosmic-ray-induced atmospheric neutrinos and misreconstructed downgoing cosmic-ray muons reveals no statistically significant neutrino point sources. We show that AMANDA-II has achieved the sensitivity required to probe known TeV gamma-ray sources such as the blazar Markarian 501 in its 1997 flaring state at a level where neutrino and gamma-ray fluxes are equal.

14.
Phys Rev Lett ; 90(25 Pt 1): 251101, 2003 Jun 27.
Article in English | MEDLINE | ID: mdl-12857122

ABSTRACT

Data from the AMANDA-B10 detector taken during the austral winter of 1997 have been searched for a diffuse flux of high energy extraterrestrial muon neutrinos. This search yielded no excess events above those expected from background atmospheric neutrinos, leading to upper limits on the extraterrestrial neutrino flux measured at the earth. For an assumed E-2 spectrum, a 90% classical confidence level upper limit has been placed at a level E2Phi(E)=8.4 x 10(-7) cm(-2) s(-1) sr(-1) GeV (for a predominant neutrino energy range 6-1000 TeV), which is the most restrictive bound placed by any neutrino detector. Some specific predicted model spectra are excluded. Interpreting these limits in terms of the flux from a cosmological distributions of sources requires the incorporation of neutrino oscillations, typically weakening the limits by a factor of 2.

15.
Hist Cienc Saude Manguinhos ; 7(2): 465-79, 2000.
Article in Portuguese | MEDLINE | ID: mdl-16680898

ABSTRACT

Plant breeding has been a human practice for some thousands of years. However, this process of domestication has made plants more vulnerable to pests and diseases. Classic plant breeding has allowed the genetic manipulation of plants through crossings with a resulting increase in crop productivity. Recently, the recombinant DNA technology has increased the possibilities of integration of exogenous genes to the plant genome, resulting in the production of transgenic plants. Despite the great debate on this issue, such plants represent to date a promising avenue for plant breeding. There are many examples of gene transference strategies which have been successful in promoting resistance to herbicides, viruses, fungi, bacteria and insects, or in producing an increase in food quality. In addition to biotechnological applications, transgenic plants have made a significant contribution to the study of gene functioning, such as the analysis of genic expression regulation and the study of protein functions codified by distinct plant genes.


Subject(s)
DNA, Recombinant , Plants, Genetically Modified , Transgenes , Agriculture/history , History, 20th Century , Plants, Genetically Modified/immunology , Plants, Genetically Modified/microbiology
17.
J Clin Oncol ; 15(5): 2118-24, 1997 May.
Article in English | MEDLINE | ID: mdl-9164226

ABSTRACT

PURPOSE: In this phase II and pharmacokinetic study, chronic, low-dose, oral etoposide was evaluated for its efficacy in patients with AIDS-related Kaposi's sarcoma who were not previously exposed to cytotoxic therapy. PATIENTS AND METHODS: Of 28 patients accrued for the study, 25 were assessable for toxicity and response. Twenty-four patients were male (homosexual or bisexual cases) and one patient was female (partner of a bisexual male). All patients were human immunodeficiency virus (HIV)-positive, New York University (NYU) disease stage IIB to IVB, and most exhibiting skin and lymph node and/or visceral disease. Median age was 33 years (range, 21 to 50), and median World Health Organization (WHO) performance status was 2 (range, 0 to 3). The patients received a mean number of six treatment courses (range, four to 27). Prior therapy included local/regional irradiation, immunotherapy (interferon-alpha), local resection, and/or cryotherapy. No prior cytotoxic therapy was allowed. Etoposide was administered at a schedule of 25 mg/m2 orally, twice a day for 7 days, every 2 weeks. Plasma concentrations of the drug were measured in six patients by a high-performance liquid chromatography (HPLC) method, after chloroform extraction using teniposide as internal standard. RESULTS: The overall response rate was 32% (two complete and six partial responses), and the median progression-free survival was 8 weeks (range, 4 to 27). Five patients (20%) had stable disease, while 12 cases (48%) did not respond. Patients without a history of opportunistic infections seemed to respond better. The regimen was well tolerated. The main toxic effects consisted of mild to moderate nausea and vomiting in approximately half of the cases, and WHO grodes 3 to 4 leukopenia and thrombocytopenia in eight of 25 (36%) and five of 25 (20%) of cases, respectively. However, only two patients had to discontinue treatment because of prolonged and severe neutropenia. No toxic deaths were documented. The pharmacokinetic analyses revealed the achievement of potentially therapeutic and lowly myelosuppressive plasma etoposide concentrations (2.1 micrograms/mL; range, 1.3 to 2.6) for a significant period of time, ie, for approximately 4.6 hours postdosing. CONCLUSION: At the schedule applied, etoposide shows significant objective antitumor activity in advanced AIDS-related Kaposi's sarcoma, and induces acceptable clinical toxicity. This apparent efficacy of the regimen could be a result of the prolonged maintenance of cytotoxic plasma concentrations of etoposide during each treatment course, and the absence of toxic peak levels of the drug. These results, together with the appreciable bioavailability of oral etoposide, make the regimen feasible for outpatient treatment of patients with advanced AIDS-related Kaposi's sarcoma. Further studies using the above-mentioned approach are warranted.


Subject(s)
Acquired Immunodeficiency Syndrome/complications , Antineoplastic Agents, Phytogenic/therapeutic use , Etoposide/therapeutic use , Sarcoma, Kaposi/drug therapy , Adult , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/pharmacokinetics , Drug Administration Schedule , Etoposide/adverse effects , Etoposide/pharmacokinetics , Female , Humans , Male , Middle Aged , Neutropenia/chemically induced , Sarcoma, Kaposi/metabolism
18.
Leukemia ; 11 Suppl 1: S28-31, 1997 Mar.
Article in English | MEDLINE | ID: mdl-9130689

ABSTRACT

The authors report on the preliminary results of an ongoing phase II trial whereby the combination of the new DNA hypomethylating agent, 5-Aza-deoxycytidine (DAC), plus daunorubicin was given as first-line induction therapy to non-pretreated patients with acute myeloid leukemia (except FAB M3). DAC was given as a 4-h intravenous infusion at the dose of 90 mg/m2 daily from days 1-5, while daunorubicin was administered at the dose of 50 mg/m2 on days 1-3. A maximum of two courses were given to the patients with an interval of 4-6 weeks. Up to now, eight patients were accrued, of those six were evaluable for toxicity and response. The main toxic effects were bone marrow suppression, mucositis, nausea and vomiting, and alopecia. All six patients achieved a complete remission after one (five cases) or two (one case) courses. The trial is open for patient accrual.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Azacitidine/analogs & derivatives , Leukemia, Myeloid, Acute/drug therapy , Adult , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Azacitidine/administration & dosage , Azacitidine/adverse effects , Azacitidine/therapeutic use , Bone Marrow/drug effects , Bone Marrow/pathology , Daunorubicin/administration & dosage , Decitabine , Drug Administration Schedule , Female , Humans , Immunophenotyping , Infusions, Intravenous , Karyotyping , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/immunology , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged
19.
FEBS Lett ; 419(1): 69-75, 1997 Dec 08.
Article in English | MEDLINE | ID: mdl-9426222

ABSTRACT

Endochitinases are widely distributed among higher plants, including a number of important crop species. They are generally considered to be involved in plant defence against potential pathogens. We have cloned a class IV chitinase gene (AtchitIV) from Arabidopsis thaliana. Southern blot analysis allowed the detection of two cross-hybridising genes in the A. thaliana genome. AtchitIV transcripts are detected in seedpods, but not in roots, inflorescence stems, leaves and flowers of healthy plants. The transcripts accumulated very rapidly in leaves after inoculation with Xanthomonas campestris. Maximum mRNA accumulation was reached one hour after infection and decreased to very low levels 72 hours after induction. This result suggests an involvement of AtchitIV in the initial events of the hypersensitive reaction. Nevertheless, A. thaliana plants transformed with the gus gene under the control of a class IV chitinase bean promoter, showed GUS activity in seed embryos. These data, together with the constitutive expression of the endogenous gene in the seedpods, points to additional physiological roles for this protein.


Subject(s)
Arabidopsis/genetics , Chitinases/genetics , Gene Expression Regulation, Plant/physiology , Xanthomonas campestris/physiology , Arabidopsis/enzymology , Arabidopsis/microbiology , Base Sequence , Chitinases/biosynthesis , Cloning, Molecular , DNA, Plant/analysis , Enzyme Induction , Gene Dosage , Genes, Plant/genetics , Molecular Sequence Data , RNA, Messenger/analysis , RNA, Plant/analysis , Recombinant Fusion Proteins , Restriction Mapping , Sequence Analysis, DNA , Sequence Homology, Amino Acid
20.
Rev Med Chir Soc Med Nat Iasi ; 85(4): 581-9, 1981.
Article in Romanian | MEDLINE | ID: mdl-25528799

ABSTRACT

Cholesterolemia in a population of 100482 inhabitants of the Bihor district, subjected to screening for the risk factors in ischemic cardiopathy were studied. Together with hyperlipidemias other risk factors were detected: arterial hypertension, obesity, diabetes mellitus, smoking, ischemic alterations of the electrocardiogram, the influence of the noxious agents present at the working place, of the blood groups and disturbances of the menstrual cycle. The mean cholesteremia is of 205 ± 43.7 mgr% (M = 207 ± 43.7 mgr%; F = 204 ± 43.5 mgr%). The prevalence of cholesterolemia, in comparison with the higher normal limits in each age group over 15 years of age, is in the entire studied series, of 13.5%. The population in whom cholesterolemia exceeds 250 mgr% represents 13.92%.


Subject(s)
Hyperlipidemias/complications , Hypertension/complications , Myocardial Ischemia/etiology , Obesity/complications , Adolescent , Adult , Age Factors , Aged , Blood Group Antigens , Body Mass Index , Diabetes Complications/epidemiology , Electrocardiography , Environmental Pollution/adverse effects , Female , Humans , Hyperlipidemias/epidemiology , Hypertension/epidemiology , Male , Mass Screening , Middle Aged , Myocardial Ischemia/epidemiology , Obesity/epidemiology , Prevalence , Risk Factors , Romania/epidemiology , Smoking/adverse effects
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