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Biomedical subjects

R Hornung

Publications and source records attributed to R Hornung.

At least 37 records · Page 2Linked to original sources
PubMed1999

Minimally-invasive debulking of ovarian cancer in the rat pelvis by means of photodynamic therapy using the pegylated photosensitizer PEG-m-THPC.

Interstitial photodynamic therapy (PDT) using the pegylated photosensitizer PEG-m-THPC was evaluated as a minimally-invasive procedure to selectively debulk unrespectable pelvic ovarian cancer (NuTu-19) in immunocompetent rats. To assess tumour selectivity, PEG-m-THPC at dosages of 0.3, 3.0 and 30 mg kg(-1) body weight was administered intravenously to 30 rats 4 weeks following tumour induction. Eight days later laser light at 652 nm and optical doses ranging from 100 to 900 J cm(-1) diffuser-length was delivered by an interstitial cylindrical diffusing fibre inserted blindly into the pelvis. Three days following light application, the volume of necrosis was measured and the damage to pelvic organs was assessed histologically on cross sections. For analysis of survival, 20 tumour-bearing rats received PDT using drug doses of 3 or 9 mg kg(-1) body weight and an optical dose of 900 J cm(-1) diffuser-length, whereas ten untreated tumour-bearing rats served as controls. The histological assessment of PDT induced necrosis showed a non-linear dose-response for both the photosensitizer dose and the optical dose. The lowest drug dose activated with the highest optical dose did not induce more necrosis than seen in tumour-bearing control animals. The same optical dose induced necrosis of 17 mm in diameter using 30 mg kg(-1) and 11 mm using 3 mg kg(-1) photosensitizer. The optical threshold for induction of significant necrosis was between 100 and 300 J cm(-1) diffuser-length for 30 mg kg(-1) and between 300 and 500 J cm(-1) for 3 mg kg(-1) PEG-m-THPC. Significant damage to normal pelvic organs was only seen if 30 mg kg(-1) photosensitizer was activated with optical doses of 700 J cm(-1) or more. In the survival study, all treated animals survived PDT for at least 2 weeks and the intestinal and urinary tract remained functional. No clinical signs of blood vessel or nerve injury were observed. Mean overall survival of untreated tumour-bearing rats was 25.0 +/- 4.5 days compared to 38.4 +/- 3.8 days and 40.0 +/- 3.6 days for rats treated with 3 mg kg(-1) or 9 mg kg(-1) PEG-m-THPC mediated PDT respectively (P < 0.05). We conclude that PEG-m-THPC mediated PDT has a favourable therapeutic window and that this minimally-invasive procedure can reduce pelvic cancer bulks effectively and selectively.

Animals↗
PubMed1999

Quantitative near-infrared spectroscopy of cervical dysplasia in vivo.

The aims of this study were: (i) to quantify near-infrared optical properties of normal cervical tissues and high-grade squamous intra-epithelial lesions (H-SIL); (ii) to assess the feasibility of differentiating normal cervical tissues from H-SIL on the basis of these properties; and (iii) to determine how cervical tissue optical properties change following photodynamic therapy (PDT) of H-SIL in vivo. Using the frequency domain photon migration technique, non-invasive measurements of normal and dysplastic ecto-cervical tissue optical properties, i.e. absorption (mu(a)) and effective scattering coefficients, and physiological parameters, i.e. tissue water and haemoglobin concentration, percentage oxygen saturation (%SO(2)), were performed on 10 patients scheduled for PDT of histologically-proven H-SIL. Cervix absorption and effective scattering parameters were up to 15% lower in H-SIL sites compared with normal cervical tissue for all wavelengths studied (674, 811, 849, 956 nm). Following PDT, all mu(a) values increased significantly, due to elevated tissue blood and water content associated with PDT-induced hyperaemia and oedema. Tissue total haemoglobin concentration ([TotHb]) and arterio-venous oxygen saturation measured in H-SIL sites were lower than normal sites ([TotHb]: 88.6 +/- 35.8 micromol/l versus 124.7 +/- 22.6 micromol/l; %SO(2): 76.5 +/- 14.7% versus 84.9 +/- 3.4%).

Adult↗
PubMed1999

Highly selective targeting of ovarian cancer with the photosensitizer PEG-m-THPC in a rat model.

Photodynamic therapy (PDT) uses light to activate a photosensitizer that has been absorbed or retained preferentially by cancer cells after systemic administration. The first pegylated photosensitizer, tetrakis-(m-methoxypolyethylene glycol) derivative of 7,8-dihydro-5,10,15,20-tetrakis(3-hydroxyphenyl)-21,23-[H]-porphyrin (PEG-m-THPC), was evaluated to target selectively unresectable pelvic ovarian cancer bulks. Our goals were two-fold: (1) to establish an ovarian cancer model suitable for the development of debulking techniques and (2) to characterize the pharmacokinetics and tumor selectivity of PEG-m-THPC by fluorescence microscopy. NuTu-19 ovarian cancer cells were injected into the caudal part of the right psoas muscle of Fisher rats. Five weeks later, 30 mg/kg body weight of PEG-m-THPC was injected intravenously. Necropsy was performed between 4 and 10 days following drug application, and fluorescence of the tumor and various abdominal organs was measured. All rats developed bulky pelvic tumors with an average diameter of 2.6 cm (+/- 0.6 SD). Tumor masses were encompassing and infiltrating pelvic organs in a similar manner to ovarian cancers in humans. Fluorescence of cancer tissue was maximal 8-10 days following drug application. At 8 days, the tumor-to-tissue ratio was 40:1 (+/- 12 SE) for most abdominal organs. We conclude that this tumor model may be used for the study of new pelvic debulking techniques, and that the tumor selectivity of PEG-m-THPC is exceptionally high 8 days after drug application. Based on these data, we are currently developing a PDT-based minimally invasive debulking technique for advanced ovarian cancer.

Animals↗
PubMed1999

Intrauterine light probe for photodynamic ablation therapy.

BACKGROUND: Endometrial ablation by means of photodynamic therapy is currently being evaluated as an outpatient treatment for dysfunctional uterine bleeding. Photodynamic therapy requires the activation of a photosensitizer by laser light. We describe a new device specifically designed to provide light delivery to the uterus for endometrial photodynamic therapy. INSTRUMENT: The intrauterine light probe consists of the three flexible optical fibers converging to one bundle resembling the shape of the uterine cavity. Each of the fibers contains a cylindrical light diffuser. EXPERIENCE: The intrauterine light probe was tested in removed human uteri for its capability to distribute light in a tissue-simulating scattering medium and to deliver sufficient light throughout the endometrium. The light distribution of the intrauterine light probe in the scattering medium is uniform on eight axes tested around the diffusing fibers. The pattern of light distribution in human uteri is similar to that in the medium. At the endomyometrial junction, there is still one third of the light applied to the endometrial surface whereas deeper in the myometrium, the light power drops to less than 10%. CONCLUSION: We propose a device that will deliver light to the uterine cavity to induce endometrial ablation by means of photodynamic therapy.

Endometrium↗
PubMed1998

Uptake of the photosensitizer benzoporphyrin derivative in human endometrium after topical application in vivo.

STUDY OBJECTIVE: To determine both the time leading to maximum endometrial drug uptake and distribution of the photosensitizer benzoporphyrin derivative-monoacid ring A (BPD-MA) after intrauterine instillation (Canadian Task Force classification ). DESIGN: Assessment of histology specimens (Canadian Task Force classification I). SETTING: University-based facility. PATIENTS: Twenty-two women scheduled for hysterectomy. INTERVENTIONS: We instilled 1.5 ml of a 2 mg/ml of BPD-MA-Hyskon solution into the uterine cavity of 22 women before hysterectomy. The fluorescence induced was measured by fluorescence microscopy on frozen sections of uterine samples from 20 of 22 patients. Systemic uptake of BPD-MA was determined in plasma of six patients by spectrofluorometry. MEASUREMENTS AND MAIN RESULTS: The BPD-MA-induced fluorescence was maximum 1 hour after instillation, with significantly higher uptake in endometrial glands than in underlying stroma. Hormonal endometrial stimulation correlated with fluorescence intensity: atrophy < secretory phase < proliferative phase. Strongest fluorescence was seen in endometrial cancer. Drug uptake by endometrial glands was found at a depth of 2 mm from the surface. Systemic uptake of BPD-MA was under the detection level of 2 ng/ml after application. CONCLUSION: Fluorescence in human endometrial glands suggests that selective destruction of human endometrium with photodynamic therapy may be possible 1 hour after topical application of BPD-MA for benign and malignant lesions. No systemic drug uptake, side effects, or major technical difficulties were detected. Limited penetration of the drug and selective uptake by endometrial glands provided a high degree of safety for endometrial ablation.

Administration, Topical↗
PubMed1998

In vivo detection of metastatic ovarian cancer by means of 5-aminolevulinic acid-induced fluorescence in a rat model.

STUDY OBJECTIVES: To determine the feasibility of macroscopic visualization of small ovarian cancer metastases in vivo by fluorescence after intravenous administration of 5-aminolevulinic acid (ALA); to assess the time after drug injection when fluorescence of small metastases is maximum; and to correlate macroscopic in vivo fluorescence with both microscopic ex vivo fluorescence and histologic findings. DESIGN: Controlled animal study (Canadian Task Force classification I). SETTING: University-based facility. SUBJECTS: Twenty-four healthy, female Fischer rats. INTERVENTION: Diffuse peritoneal metastatic cancer was induced in Fischer 344 rats by intraperitoneal injection of 1 million syngeneic ovarian cancer cells (NuTu-19). Four weeks after induction ALA100 mg/kg was injected intravenously, and diagnostic laparotomy was performed 1, 3, 6, or 9 hours thereafter. MEASUREMENTS AND MAIN RESULTS: The peritoneal cavity was illuminated with the Wood's lamp (ultraviolet light). Fluorescence was determined by direct visualization and compared with a calibrated fluorescent disk. Tissues were collected, sectioned, and examined by fluorescence and conventional light microscopy. Within 1 to 3 hours after intravenous injection of ALA, in vivo fluorescence of tumor nodules (diameter 0.4-5.0 mm) was macroscopically visible. Tumor-free peritoneum did not show fluorescence and was significantly distinguishable from cancer nodules. Fluorescence from intestinal tissues was comparable with tumor nodules. Microscopic fluorescence analysis showed similar values for tumor nodules and peritoneum. Stained histologic specimens of peritoneal surface revealed a superficial layer of cancer cells responsible for fluorescence. The time course of the fluorescence curve in the intestine peaked twice, at 1 and 6 hours after ALA injection. Macroscopically fluorescing nodules were histology confirmed as malignant. CONCLUSIONS: Fluorescence detection of small cancer nodules after intravenous injection of ALA is feasible for nodules smaller than 0.5 mm on the peritoneum. One to 3 hours after drug injection is optimal for diagnosis of metastases.

Aminolevulinic Acid↗
PubMed1998

Exposure assessment for a study of workers exposed to acrylonitrile.

Procedures used to develop estimates of exposure to acrylonitrile for a cohort study (>25000 workers in 8 monomer, fiber, and resin companies from 1952 to 1983) are presented. Visits to the companies were made, interviews of workers were conducted, historical records were made, and measurements were taken. On the basis of similar tasks, locations, other exposures, and a similar distribution of exposures to acrylonitrile, 3600 exposure groups were formed. Special procedures were used to reduce the misclassification of workers performing tasks that varied in time but that were inadequately reflected in the job title. A software program organized and retained all exposure information on each exposure group. Quantitative estimates of acrylonitrile exposure were developed using a hierarchical approach in a software program that documented the derivation of each estimate and facilitated data review. Two of the estimation methods were evaluated in a comparison with measurement data.

Acrylonitrile↗
PubMed1998

m-THPC-mediated photodynamic therapy (PDT) does not induce resistance to chemotherapy, radiotherapy or PDT on human breast cancer cells in vitro.

Photodynamic therapy (PDT) uses laser light to activate a photosensitizer that has been absorbed preferentially by cancer cells after systemic administration. A phototoxic reaction ensues resulting in cell death and tissue necrosis. Some cells, however, may survive PDT. This study was performed to determine if surviving human breast cancer cells (MCF-7) can become resistant to PDT, chemotherapy or radiotherapy. The MCF-7 cells were cultured under standard conditions prior to being exposed to the photosensitizer, 5,10,15,20-meta-tetra(hydroxyphenyl)chlorin (m-THPC), for 24 h and then irradiated with laser light (652 nm). Surviving cells were allowed to regrow by allowing a 2 week interval between each additional PDT. After the third and final treatment, colony formation assays were used to evaluate the sensitivity of cultured cells to ionizing radiation and PDT and the ATP cell viability assay tested in vitro chemosensitivity. Flow cytometry was used to analyze the cell cycle. No alterations in the cell cycle were observed after three cycles of PDT with m-THPC. Similar responses to chemotherapy and ionizing radiation were seen in control and treatment groups. The m-THPC-sensitized PDT did not induce resistance to subsequent cycles of PDT, chemo- or radiotherapy. Photodynamic therapy with m-THPC may represent a novel adjunctive treatment of breast cancer that may be combined with surgery, chemotherapy or ionizing radiation.

Antineoplastic Agents↗
PubMed1997

In vitro effects and localisation of the photosensitizers m-THPC and m-THPC MD on carcinoma cells of the human breast (MCF-7) and Chinese hamster fibroblasts (V-79).

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) is the combination of a photosensitizer with laser light to induce preferential destruction of malignant cells. In this study two new photosensitizers--5,10,15,20-meta-tetra(hydroxyphenyl) chlorin (m-THPC) and m-THPC MethoxyPEG2000 derivative (m-THPC MD)--were tested, both for their dark toxicity, i.e., cytotoxicity in the absence of light, and for their light-induced cytotoxicity in mammalian cell cultures. STUDY DESIGN/MATERIALS AND METHODS: Cell lines used were MCF-7 (human breast carcinoma) and V-79 (Chinese hamster lung fibroblast). After cultivation under standard conditions, cells were administered the photosensitizers and 24 hr later exposed to various energy levels of laser light at a wavelength of 652 nm. Cell survival was monitored using a clonogenic assay and was expressed as the surviving fraction of the untreated control. RESULTS: Up to an m-THPC concentration of 1 microgram/ml, no dark toxicity was observed; at higher concentrations a rapid fall in survival occurred. m-THPC MD showed no dark toxicity up to 100 micrograms/ml. In vitro m-THPC was approximately 10 times more cytotoxic than m-THPC MD. The MCF-7 and V-79 cell lines displayed similar responses to PDT. CONCLUSIONS: Both m-THPC and m-THPC MD are very efficient photosensitizers in vitro. Up to the therapeutic dose, neither exhibited dark toxicity. There is clinical relevance of the photosensitizers by a large therapeutic index.

Animals↗
PubMed1997

Proposed model for estimating dose to inhabitants of 60Co contaminated buildings.

A model to predict the time weighted exposures to gamma radiation was developed for buildings constructed with structural steel having some contamination from 60Co. Several buildings throughout sixteen city blocks in downtown Taipei were built about ten years ago with this material. These buildings were used for residential, business, and educational purposes with radiation levels ranging from background to five hundred times background. A comprehensive epidemiologic study by the National Yang Ming University Medical School in Taipei is underway to study the effects of this exposure to the building occupants. An evaluation of external radiation exposure was performed using survey instruments and thermoluminescent dosimeters. Exposure data from the survey instruments were used in a computer model developed to calculate cumulative radiation exposure estimates for the epidemiologic research. While the survey instrument data provided radiation levels at a point in time, the thermoluminescent dosimeters were placed in fixed locations and on several volunteers for a period of one month to verify the modeling results. The model itself is a mathematical algorithm that provides estimates with minimum and maximum range values by taking into account differences in the survey data between adults and children, variable occupancy patterns, background radiation, and radioactive decay. Several assumptions (background rates, height adjustment values, and occupancy factors) are easily adjusted to improve the estimated radiation exposures. The model predicted the exposures as measured by the thermoluminescent dosimeters with greater reliability for adults than for children. The differences between the two methods were about 10-15% for the adults and about 60% for the child. This strategy, its advantages, limitations, and its performance against actual thermoluminescent dosimeter measurements are presented.

Activities of Daily Living↗
PubMed1996

Risk of low red or white blood cell count related to estimated benzene exposure in a rubberworker cohort (1940-1975)

This study evaluated the relationship between benzene exposure and low white blood cell (WBC) and red blood cell (RBC) counts. Hematologic screening data collected over a 35 year period at a rubber hydrochloride manufacturing plant were analyzed; an increased risk of leukemia had been demonstrated previously among workers at the plant [Infante et al. (1977).' Lancet 2:76-78; Rinsky et al. (1981): Am J Ind Med 2:217-45 (1987): NEJM 316:1044-1050/. Hematologic screening data were available for 657 of 1,037 (63.3%) individuals employed at the plant from 1939 through 1976. There was a total of 21. 710 blood test records (range per individual 1-354). The study utilized a case-control design and estimated benzene exposures using the job exposure matrix developed by Rinsky et al. (1987): NEJM 316:1044-1050]. The effects of benzene exposure in the 30, 90, and 180 days before the blood test date, as well as cumulative exposure up until the blood test date, were examined using conditional logistic regression. For WBCs there was a strong exposure response and all of the exposure metrics selected showed a significant relationship with low blood count. For RBCs there was a weak positive exposure-response, which was significant (p = 0.03) for one of the dose metrics. The finding of an exposure-response relationship in the range of exposures represented in this study, where the maximum daily benzene exposure estimate was 34 ppm, is consistent with findings of several animal studies demonstrating a decrease in peripheral lymphocyte counts at benzene exposures as low as 10 ppm, and a stronger effect of benzene exposure on lymphocytes (as reflected in total WBC count) than on red cells. There was no evidence for a threshold for the hematologic effects of benzene exposure, suggesting that even exposure to relatively low levels of benzene (e.g., <5 ppm) may result in hematologic suppression.

Benzene↗
PubMed1996

[Evaluation of the smoking cessation course (1984-1990) of the Cancer and Lung Society of canton Zurich].

The present study is to evaluate the smoking cessation therapy of the working team of the Cancer Association and Lung Association of the State of Zurich. Roughly 1/3 of all 913 participants of the therapy from 1984 to July 1990 have responded to the survey. Of these 1/3, more than a quarter did not smoke any more one year after the therapy. An antismoking program with a 1-year smoking cessation rate of 20 to 30% is considered successful in professional circles. The smoking cessation rate of all 913 therapy participants is probably below the 27% obtained in as much as the share of the successful ones among those replying, by experience is bigger than the share of those failling. Also the more precise inquiry in the first 7 therapies of 1990 confirms these findings. There the rate of success is barely 15% after 1 to 1 1/2 year. It cannot be ascertained whether the smoking cessation rate of all therapy courses is that high or only at the time after the program restructurations at the beginning of 1990. Only a precise achievement control can guarantee a consequent and continuous therapy evaluation within the next years.

Adolescent↗
PubMed1996

A comparison of dermatologists and generalists. Management of childhood atopic dermatitis.

BACKGROUND AND DESIGN: To compare the approaches of generalist physicians and dermatologists in the management of childhood atopic dermatitis (AD), a 6-page questionnaire was developed to assess specific practice characteristics and therapeutic preferences. Surveys were mailed to all board-certified dermatologists in North Carolina (n = 173) and to a sample of pediatricians (n = 200) and family medicine physicians (n = 300) randomly selected from the North Carolina Health Professions Database. There were 307 eligible respondents, defined as those who see children with AD, and 112 ineligible respondents. The response rate of eligible respondents was 62%. The specialty-specific response rates were as follows: 76% for dermatologists, 70% for pediatricians, and 49% for family medicine physicians. RESULTS: Dermatologists reported seeing the largest number of patients with AD, followed by pediatricians and family medicine physicians. Dermatologists also reported seeing the highest percentage of pediatric patients with moderate or severe AD (59%), followed by pediatricians (27%) and family medicine physicians (19%). Regardless of the severity of the AD, dermatologists consistently indicated a greater preference for more intensive therapy compared with generalists, as demonstrated by their preference for prescribing more potent topical steroids. Also, dermatologists were more likely than pediatricians (22%) and family medicine physicians (8%) to report "frequent use" of oral antibiotics for AD (63%). CONCLUSIONS: These striking interspecialty differences are likely to affect the outcome and cost of care of childhood AD. The data support the argument for conducting further studies of generalists' and dermatologists' approach to childhood AD, correlating therapeutic approaches with clinical outcomes and costs.

Child↗
PubMed1995

Two new applications for the first dorsal metacarpal artery pedicle in the treatment of severe hand injuries.

Two new indications for the use of the first dorsal metacarpal artery (1st DMA) in reconstruction following severe hand injury are reported. In the first case, a primary pollicization of the index finger was based solely on the dorsal arterial network. The second case involves a microvascular arterial revascularisation of a 1st dorsal metacarpal artery island flap. Neither procedure has previously been described.

Arteries↗
PubMed1995

Psychosocial factors predict medical outcome following a first myocardial infarction. Working Group on Cardiac Rehabilitation of the Swiss Society of Cardiology.

BACKGROUND: The aim of this study was to identify psychosocial variables that, in addition to known medical factors, predict the long-term outcome after a first myocardial infarction. PATIENTS AND METHODS: The study population consisted of 222 men aged 30-60 years who entered an inpatient rehabilitation program a mean of 7 weeks after a first myocardial infarction. Medical data and completed questionnaires for psychosocial variables were obtained from the patients and their family physicians at entry to the rehabilitation center and 1 year later. Further data, including answers to a detailed questionnaire, were collected at the beginning of rehabilitation and after one year; this follow-up was 99% complete. RESULTS: The 1-year mortality was 2.2%, the reinfarction rate 1.8%, hospital readmissions for cardiac reasons occurred in 25%, and 13% of the patients underwent a subsequent revascularization procedure. At baseline and after 1 year, respectively, 84 and 83% of the patients were asymptomatic. A poor medical outcome, defined as death, reinfarction, severe symptoms or poor exercise capacity, was seen in 9% of the patients. The most important physiological predictors for an unfavourable medical outcome, found in bivariate and multivariate analyses, were age, severity of infarction, and major coronary risk factors. In addition, some of the psychosocial variables were significantly related to a poor medical outcome: lack of a stable partnership, high work load, poor general well-being with multiple chronic non-specific health complaints, and a low external locus of control (failure to identify disease-promoting factors within own surroundings or lifestyle). CONCLUSIONS: The medical course of coronary artery disease was predicted not only by medical variables but also by psychological and social variables. As well as being addressed directly, these factors may help to identify patients who need to be followed more closely, so that medical complications can be reduced by treating early signs of disease progression more aggressively.

Adult↗