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Biomedical subjects

H Koren

Publications and source records attributed to H Koren.

At least 19 recordsLinked to original sources
PubMed1998

Experimental assessment of the influence of atmospheric pollutants on respiratory disease.

Asthma is a chronic respiratory disease characterized by inflammation, episodes of usually reversible airways obstruction, and bronchial hyperresponsiveness. The disease has significant health, societal and economic consequences. Experimental assessment methods, including controlled human exposure studies, human and animal dosimetry, as well as animal and in vitro toxicology, can shed light on how air pollutants may cause and/or worsen asthma. A brief summary background on selected classes of air pollutants is provided and selected experimental studies that exemplify novel approaches or suggest new hypotheses are highlighted. Possible directions for future research about the effects of particles, pesticides, ambient air toxicants, and pollutant mixtures on asthma, are also outlined.

Air Pollutants↗
PubMed1997

UVA II exposure of human skin results in decreased immunization capacity, increased induction of tolerance and a unique pattern of epidermal antigen-presenting cell alteration.

The risks incurred from increased exposure to UVA II (320-340 nm) (i.e. during sunscreen use and extended outdoor exposure, tanning parlors) are not well understood. Therefore, we explored the effects of UVA II on skin immune responses in humans. After a single local exposure (4 minimum erythemal dose [MED]) using a xenon are lamp filtered with a narrow bandpass filter (335 +/- 5 nm full width at half maximum), individuals were contact-sensitized with dinitrochlorobenzene (DNCB) through a UVA II exposure site or through normal skin. UVA II induced a marked decrease in the magnitude of skin immune responses (P < 0.0001). The UVA II group had only 29% successful sensitizations, as compared to 83% in the control group. The percentage of individuals who remained tolerant to DNCB after two sensitizations was 23.6% for the UVA II-exposed group, as compared to 3.8% in the controls (P = 0.006). UVA II also uniquely altered the type of antigen-presenting cells present in the epidermis. Human leukocyte antigen (HLA)-DR+ cells in control epidermal cell suspensions (C-EC) comprised a single, homogeneous population of Langerhans cells (LC) with the phenotype: CD1ahi DRmid CD11b CD36 (1.5 +/- 0.3% of EC). UVA II irradiation reduced the number of such LC to 0.6 +/- 0.2% of EC. Although cells expressing the macrophage phenotype: CD1a- DRhi CD11b+ CD36+ were increased in UVA II skin, relative to C-EC, these comprised only 10.1 +/- 6.1% of the DR+ cells, which is less than that after UVB exposure. Also distinct from UVB, a third population was found in UVA II-EC, which exhibited a novel phenotype: CD1a+ DR+ CD36+ CD11b+; these comprised 11.1 +/- 6.9% of the DR+ UVA II-EC. In conclusion, despite the above differences in infiltrating DR+ cells, both UVB and UVA II reduce the skin's ability to support contact sensitization, induce active suppression (tolerance) and induce a reduction in LC.

Adaptation, Physiological↗
PubMed1996

Induratio penis plastica: effectivity of low-dose radiotherapy at different clinical stages.

This study describes the treatment of Peyronie's disease by means of low-dose radiotherapy. We treated 265 men aged 24.5-79.4 years (median = 57.7 years). No previous therapy had been carried out in 214 patients, and 41 patients had been pretreated (systemic: potassium p-aminobenzoate, vitamins a, b, e; topical: corticosteroids, teleradiotherapy). The disease was classified using criteria proposed by Alth in 1984 location, number and size of foci, hardness of fibromatous foci and axis deviation, potentia coeundi and pain were evaluated). Radiotherapy was performed by local application of a special iridium-192 moulage developed at our institute. In 66.4% of the monitored patient group (n = 155) therapy was successful. We obtained complete regression of the fibromatous foci in 9% (n = 14), partial remission > 50% in 29.7% (n = 46) and partial remission < 50% in 27.7% (n = 43) of the patients. We found a significant correlation between hardness, size of the treated foci and therapeutic success. Eighty-three patients suffered from pain during penile erection before therapy, and in 61.4% (n = 51) of these patients the pain disappeared after treatment. Moreover, the patients confirmed that both loss of pain and regression of deviation related to foci regressions were correlated with improvement in erectile function. No serious side effects were observed in any of our patients.

Adult↗
PubMed1996

Hypericin in phototherapy.

We describe the first local use of hypericin as photosensitizer for photodynamic therapy in a patient with recurrent malignant mesothelioma. Hypericin is a polycyclic quinone, which has been shown to possess in vivo and in vitro antiretroviral and photosensitizing activity; moreover, it is used in depressive disorders. The semiquinone radical, singlet oxygen, and superoxide anion radical are reported to be the toxic agents in hypericin phototherapy. Our first experience with locally applied hypericin in a superficial tumor-plate was performed 8 weeks after the systemic administration of hematoporphyrin derivatives. For tumor light illumination we used an argon pumped dye laser tuned to 632 nm. Owing to satisfactory results, we repeated the same therapy 4 weeks later- and no therapeutic effect was noted. Following this, we proved the interstitial application of HPD and the combination of interstitial HDP and superficially applied hypericin. The subsequent light illumination 6 hours later had no efficacy in the HDP-photosensitized area but there was tumor destruction in the field with both administered photosensitizers. Our first experience suggests a potentiation of two photosensitizers: hematoporphyrin derivatives and hypericin.

Aged↗
PubMed1996

Photodynamic therapy in gynaecologic cancer.

We started photodynamic therapy in gynaecologic tumors in 1988. Seven patients with endometrial carcinomas stage FIGO 1a (restricted to the endometrium) were treated primarily and also 4 patients with recurrences of vaginal and vault cervix carcinoma, carcinoma of the corpus uteri and the vulva. Residual tumors after conventional therapy of cervix and vulvar carcinoma were treated in 2 patients. Tumor illumination was performed by an Argon dye laser 24-72 h following the intravenous administration of haematoporphyrin derivatives (HPD) (Photosan III, 2 mg kg-1 body weight). The intracavitary tumor irradiation by means of a glass fibre was controlled by ultrasound. Superficial and small lesions of vaginal and vulvar carcinomas were subjected to superficial light irradiation; whereas tumors exceeding 1 cm in depth were treated interstitially. Tumor response was estimated 1 month after therapy. Complete remission was achieved in 8 patients, partial remission in 2, and no remission in 3 cases. Subsequent radiotherapy was performed in 3 patients with bleeding endometrial cancer with consecutive complete response.

Adenocarcinoma↗
PubMed1996

Experiences of photodynamic therapy in dermatology.

From March 1988 to May 1994, 15 patients underwent the treatment protocol of superficial photodynamic therapy (PDT) in dermatological localized malignancies. Two tumours (one M. Queyrat of the penis, one basalioma) were treated primarily; the other 13 patients experienced relapses of underlying disease after treatment by surgery, radiotherapy or chemotherapy. Most of the patients (10/15) received doses of 2 mg Photosan III kg-1 body weight (BW), four received a lower dose of 1-1.5 mg kg-1 BW and one patient received 3 mg kg-1 BW. Only one remarkable side-effect (tachyarrhythmia) during Photosan III infusion occurred. All patients were treated by an argon dye laser system. The light dose was 200 J cm-2 (11 patients) and 150 J cm-2 (four patients). Complete response occurred in six lesions, including one M. Queyrat and five basaliomas. Two patients had significant partial response with distinct regression of tumour (one pretreated basalioma of the upper lip and one superficially spreading mesothelioma of the scrotum). Five patients (all basaliomas) demonstrated only local response and two patients gave no response (one basalioma, one melanoma metastasis). The results obtained from this small sample suggest the necessity of an optical dosimetric system. At present, PDT should be restricted for selected or pretreated cases.

Basal Cell Carcinoma↗
PubMed1996

Hearing-aid pre-selection through a neural network.

Selection of optimal hearing aids for a patient with a particular audiogram has become increasingly difficult as the number of available models on the market has grown considerably. In order to assist the hearing-aid fitter in this work, recent programming techniques using artificial neural networks have been investigated. Artificial neural networks are capable of recognizing audiograms and relating them to suitable hearing aids. A programme to assist in the early stage of hearing-aid selection was developed using these techniques.

Audiometry↗
PubMed1994

Photodynamic therapy--an alternative pathway in the treatment of recurrent breast cancer.

PURPOSE: Validity of photodynamic therapy for treatment of recurrent breast cancer. METHODS AND MATERIALS: Patients were intravenously administered with a metal-free haematoporphyrine derivative for tumor sensibilization. For irradiation both monochromatic and white light was used. Monochromatic light at a wavelength of 632 nm was supplied by an Argon-Dye laser, whereas a halogen lamp provided white light. Narrowband red light came into use in case of one patient. Therapy included recurrent diseases of breast carcinoma, especially disseminary skin metastases, local recurrences, and lymphangiosis. Classical pretreatment was ineffective for the therapeuted patient group. RESULTS: The healing potency of photodynamic therapy for our patient group is enumerated in detail. No differences in the therapeutic effect were seen using either Argon Dye laser or noncoherent light sources. CONCLUSION: Photodynamic therapy appears to be a valuable treatment to classical therapeutic intervention providing a selective destruction of tumor cells without further affecting life quality.

Adult↗
PubMed1993

A quantitative determination of singlet oxygen with horseradish peroxidase.

A singlet oxygen determination method based on the formation of dimethyl-(2,5)-2-methoxy-5-hydroperoxydihydrofuran (DMFO2) followed by acid hydrolysis with 0.1 N H2SO4 is described. Hydrogen peroxide is formed thereby as a product of hydrolysis which is then determined by the horseradish peroxidase-catalyzed formation of the homovanillic acid dimer. Since DMFO2 is a crystalline compound with sufficient stability it can be used as a primary standard for the determination. The peroxidase-catalyzed hydrogen peroxide determination allows detection of singlet oxygen concentrations as low as 10(-7) M.

Free Radicals↗
PubMed1993

Ambient ozone causes upper airways inflammation in children.

Ozone constitutes a major air pollutant in Western Europe. During the summer national air quality standards are frequently exceeded, which justifies concern about the health effects of ozone at ambient concentrations. We studied upper airways inflammation after ozone exposure in 44 children by repeated nasal lavages from May to October 1991. During this time period five to eight lavages were performed for each child. On 14 days following high ozone exposure (daily maximum > or = 180 micrograms/m3) 148 nasal lavages were performed, and on 10 days following low ozone exposure (daily maximum < or = 140 micrograms/m3) 106 nasal lavages were performed. A significant increase of intra-individual mean polymorphonuclear leukocytes (PMN) counts from low ozone days (median, 20.27 x 10(3)) to high ozone days (median, 27.38 x 10(3); p < 0.01) was observed. Concomitant with a decrease of ozone concentrations in the fall mean PMN counts showed a downward trend. Linear regression analysis of log-PMN counts yielded a significant effect for ozone (p = 0.017). In a subsample humoral markers of inflammation were measured for each child's highest and lowest exposure. A significant increase was observed for eosinophilic cationic protein (median, 77.39 micrograms/L on low ozone days versus 138.6 micrograms/L on high ozone days; p < 0.05). Thus we conclude that ozone at ambient concentrations initiates a reversible inflammatory response of the upper airways in normal children.

Air Pollutants↗
PubMed1992

UV exposure reduces immunization rates and promotes tolerance to epicutaneous antigens in humans: relationship to dose, CD1a-DR+ epidermal macrophage induction, and Langerhans cell depletion.

Increasing UVB radiation at the earth's surface might have adverse effects on in vivo immunologic responses in humans. We prospectively randomized subjects to test whether epicutaneous immunization is altered by prior administration of biologically equalized doses of UV radiation. Multiple doses of antigens on upper inner arm skin (UV protected) were used to elicit contact sensitivity responses, which were quantitated by measuring increases in skin thickness. If a dose of UVB sufficient to induce redness (erythemagenic) was administered to the immunization site prior to sensitization with dinitrochlorobenzene (DNCB), we noted a marked reduction in the degree of sensitization (P less than 0.0006) that was highly dose responsive (r = 0.98). Even suberythemagenic UV (less than a visible sunburn) resulted in a decreased frequency of strongly positive responses (32%) as compared to controls (73%) (P = 0.019). The rate of immunologic tolerance to DNCB (active suppression of a subsequent repeat immunization) in the groups that were initially sensitized on skin receiving erythemagenic doses of UV was 31% (P = 0.0003). In addition, a localized moderate sunburn appeared to modulate immunization with diphenylcyclopropenone through a distant, unirradiated site (41% weak responses) as compared to the control group (9%) (P = 0.05). Monitoring antigen presenting cell content in the epidermis revealed that erythemagenic regimens induced CD1a-DR+ macrophages and depleted Langerhans cells. In conclusion, relevant and even subclinical levels of UV exposure have significant down modulatory effects on the ability of humans to generate a T-cell-mediated response to antigens introduced through irradiated skin.

Antigens, CD↗
PubMed1990

Tissue factor and factor VII messenger RNAs in human alveolar macrophages: effects of breathing ozone.

This study was performed to determine if genes for tissue factor and factor VII proteins are expressed and regulated in vivo in lung macrophages during inflammation. Human alveolar macrophages and alveolar fluids were obtained 18 hours after healthy male adults were exposed, for 2 hours during intermittent exercise, to either air or air with 0.4 ppm ozone, added as a model toxic respiratory agent. Messenger RNA (mRNA) for both tissue factor and factor VII were demonstrated in macrophages isolated after subjects were exposed to unpolluted control air. With the same subjects examined after breathing ozone, the following changes were observed: tissue factor mRNA concentration in macrophages increased 2.6 +/- 0.47-fold. Factor VII mRNA concentration was reduced 0.64 +/- 0.24-fold. Total numbers of macrophages recovered did not change significantly. Ratios of nuclear:cytoplasmic areas of cytocentrifuged macrophages were augmented by 24.8% +/- 3%, giving morphometric evidence that immature cell forms increased in the population. In the lavage, tissue factor activity was increased 2.1 +/- 0.3-fold, while amounts of lipid phosphorous, which estimate total membrane lipids, and estimated volumes of alveolar fluid were not significantly changed. Factor VII activity and fibrinopeptide A levels in lavage were increased approximately twofold. These results using rapidly isolated, noncultured cells indicate that tissue factor and factor VII mRNA are synthesized in the alveolar macrophage population in vivo. In addition, evidence was found that as a result of breathing ozone, a shift in alveolar macrophage maturity occurred in association with tissue factor mRNA, tissue factor activity, and factor VII activity increases, and with formation of fibrinopeptide A in alveolar fluids.

Adult↗
PubMed1990

Phase I studies of recombinant interferon-gamma.

A phase I study of the effects of intravenous administration of interferon-gamma on 31 patients was performed. The effects of dose, schedule, and chronic administration were studied. In the first phase of the study, a dose range of 0.01-500 MU/m2 (0.0002-25 mg/m2) was tested and we found the maximum tolerated dose to be 400 MU/m2; the dose-limiting toxicity with this preparation was hypotension. In the second phase, three different schedules of administration were tested. There were no significant differences in toxicity between a 20 min, a 4 h, or a 24 h infusion of 60 MU/m2 (3 mg/m2). In the third phase, patients received chronic administration of either 1 or 30 MU/m2. Patients given 30 MU/m2 twice a week for 4 weeks showed more symptoms--fever, nausea, and orthostasis--than those treated with 1 MU/m2. No significant changes were seen in natural killer cell activity, antibody-dependent complement cytotoxicity, or monocyte cytotoxicity at any dose. Maximal stimulation of 2',5'-oligodenylate synthetase occurred at low doses (12 MU/m2). Depressed bone marrow colony formation for CFU-GM, BFU-E, and CFU-GEMM in vivo was noted. No objective antitumor responses were noted. This preparation of recombinant interferon-gamma can be given in doses as high as 400 MU/m2. Chronic administration would appear to be limited to 30 MU/m2. However, lower doses may give maximal biologic responses. These studies provide further information on the biologic effects of a wide dose range and a variety of schedules of recombinant interferon-gamma.

2',5'-Oligoadenylate Synthetase↗
PubMed1989

A method for comparison of animal and human alveolar dose and toxic effect of inhaled ozone.

Present models for predicting the pulmonary toxicity of O3 in humans from the toxic effects observed in animals rely on dosimetric measurements of O3 mass balance and species comparisons of mechanisms that protect tissue against O3. The goal of the study described was to identify a method to directly compare O3 dose and effect in animals and humans using bronchoalveolar lavage fluid markers. The feasibility of estimating O3 dose to alveoli of animals and humans was demonstrated through assay of reaction products of 18O-labeled O3 in lung surfactant and macrophage pellets of rabbits. The feasibility of using lung lavage fluid protein measurements to quantify the O3 toxic response in humans was demonstrated by the finding of significantly increased lung lavage protein in 10 subjects exposed to 0.4 ppm O3 for 2 h with intermittent periods of heavy exercise. The validity of using the lavage protein marker to quantify the response in animals has already been established. The positive results obtained in both the 18O3 and the lavage protein studies reported here suggest that it should be possible to obtain a direct comparison of both alveolar dose and toxic effect of O3 to alveoli of animals or humans.

Administration, Inhalation↗