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Biomedical subjects

P Wyss

Publications and source records attributed to P Wyss.

At least 37 records · Page 2Linked to original sources
PubMed1996

Accumulation of 5-aminolevulinic acid-induced protoporphyrin IX in normal and neoplastic human endometrial epithelial cells.

The aim of this study was to evaluate 5-Aminolevulinic acid (ALA)-induced fluorescence of normal and neoplastic endometrial epithelial cells for diagnosis and photodynamic treatment. Fluorescence of ALA-induced PpIX in vitro was measured by flow cytometry in two different human endometrial adenocarcinoma cell lines and in normal cells cultivated from fresh endometrial tissue of three premenopausal patients. The cells were analysed after incubation with different concentrations of ALA during 3, 6, or 24 hours. Both tumor cell lines showed a statistically significant higher fluorescence of PpIX than normal epithelial cells after incubation with 1 mg ALA per ml medium during 24 hours. The well-differentiated cancer cells produced significantly more PpIX than the poorly differentiated cancer cells. Relative PpIX intensity of the two cancer cell lines correlated with cell proliferation rate as measured by the doubling times of the cells. Higher accumulation of Pp IX in neoplastic endometrium compared to normal endometrial epithelial cells may provide targeted biopsies and selective photodynamic destruction of neoplastic micro-lesions.

Adenocarcinoma↗
PubMed1996

Dosimetry model for photodynamic therapy with topically administered photosensitizers.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) based on topical application of photosensitizers has been under development over the last years. Typical applications are treatment of basal cell carcinoma of the skin and photoablation of the endometrium. The dosimetry for topically administered photosensitizers must take a time-dependent inhomogenous drug distribution into account together with the conventional parameters such as optical scattering, absorption, and photobleaching. STUDY DESIGN/MATERIALS AND METHODS: This study presents a dosimetry model where the cytotoxic dose is calculated in a stepwise procedure. The first step calculates the time-dependent distribution of 5-aminolevulinic acid (5-ALA) from diffusion theory. In skin this distribution is dependent on drug permeability through the stratum corneum, on the diffusivity of dermis and epidermis, on the drug clearance time, and on the conversion rate from 5-ALA to protoporphyrin IX (PpIX). In the second step the distribution of PpIX is calculated from the 5-ALA distribution found in the first step taking the dynamics of the biosynthesis of 5-ALA to PpIX and the clearance time of PpIX into account. In the third step the generation of cytotoxic singlet oxygen is calculated from the optical distribution during irradiation, taking a photobleaching mechanism into account. RESULTS: The distribution of cytotoxic oxygen is predicted from the optical dose, the drug dose, and the time between the application of the drug and the irradiation. CONCLUSION: The presented dosimetry model is made as simple as possible, yet composite enough to enable all relevant parameters to be taken into account. The model that is based on a linear theory in a semi-infinite medium can, if required, be extended to take nonuniform and nonlinear phenomena into account.

Administration, Topical↗
PubMed1996

Photosensitization of the rat endometrium following 5-aminolevulinic acid induced photodynamic therapy.

BACKGROUND AND OBJECTIVE: The impact of photodynamic therapy (PDT) on the endometrium following topical application of 5-aminolevulinic acid (ALA) was studied in a rat model. Study Design/ MATERIALS AND METHODS: Fluorescence microscopy revealed peak ALA to protoporphyrin IX (Pp IX) conversion 3-6 hours after application. Significantly higher Pp IX levels were observed in the endometrial glands compared with endometrial stroma and myometrium. RESULTS: Histological studies showed PDT-induced endometrial destruction with atrophy 7-10 weeks after treatment. Reproductive performance studies demonstrated significant implantation failure in the treated uterine horns compared with controls. The number of implantation sacs in the treated and untreated horns was 0.4 +/- 0.3 and 8.9 +/- 1.0, respectively (P < 0.01). CONCLUSION: We conclude that the high rate of Pp IX conversion in the endometrial glands can be exploited to treat dysfunctional uterine bleeding with PDT. In addition, this concept may also be applied to study endometrial regeneration and embryo implantation mechanisms.

Administration, Topical↗
PubMed1996

Selective photosensitizer localization in the human endometrium after intrauterine application of 5-aminolevulinic acid.

OBJECTIVE: Our purpose was twofold: to determine the distribution of the endogenous photosensitizer protoporphyrin IX in the uterus and to ascertain the time interval leading to maximal endometrial fluorescence after intrauterine instillation of 5-aminolevulinic acid. STUDY DESIGN: One milliliter of a 400 mg/ml 5-aminolevulinic acid-Hyskon solution was instilled into the uterine cavity of 27 women before hysterectomy. On frozen sections of uterine samples 5-aminolevulinic acid-induced fluorescence was measured with fluorescence microscopy. RESULTS: 5-Aminolevulinic acid-induced fluorescence could first be detected in the superficial endometrial glands 75 minutes after drug injection. In the endometrial gland stumps fluorescence intensity peaked 4 to 8 hours after 5-aminolevulinic acid instillation and was > 48 times higher than in the underlying myometrium. CONCLUSIONS: Fluorescence in the endometrial glands suggests that selective photodynamic destruction of the endometrium may be possible 4 to 8 hours after intrauterine 5-aminolevulinic acid instillation.

Aminolevulinic Acid↗
PubMed1996

Axillary lymphadenectomy--just how radical should it be?

UNLABELLED: To determine whether local axillary recurrences correlate with the number of lymph nodes extirpated, 779 cases of breast cancer were analysed in retrospect. RESULTS: The number of lymph nodes extirpated varied between 1 and 42 per axilla. The axillary recurrence rate of 5.5% showed a minimal correlation between the frequency of these recurrences and the number of lymph nodes removed. There is an equally insignificant correlation between the percentage of positive histological findings and the number of lymph nodes extirpated: The trend analysis shows that with fewer than five lymph nodes extirpated, 40% of positive histological findings can be expected, whereas with over 20 lymph nodes extirpated the percentage is 45%. CONCLUSION: The number of lymph nodes extirpated is an unsuitable indicator as to how radical axillary clearance is. Surgeons should rely on anatomical boundaries rather than focusing on the number of lymph nodes removed.

Adult↗
PubMed1996

[Benzoporphyrin derivative mono acid for photodynamic therapy of the endometrium].

The aim was to study the impact of photodynamic therapy (PDT) on the endometrium after local intrauterine application of photosensitiser (Ps) and laser light without sensitising the skin. To our knowledge Benzoporphyrin Derivative Mono Acid (BPD) was used for the first time for this purpose in the rat model. The advantage of using BPD is the fact that light of 690 nm (maximum absorption) penetrates deeper into tissue and shows less absorption by haemoglobin. Low-light level tissue fluorescence imaging revealed a distinct positive endometrium-to-myometrium ratio within the first 12 hours. Relative fluorescence was highest in the endometrial glands and lowest in the myometrium. After 12 hours the intensity of fluorescence levelled off in all compartments and values of the glands approached close to those of the other layers. REPRODUCTIVE PERFORMANCE AFTER PDT: There was a significant difference in nidations (p < 0.03) in the treated left uterine horn as compared to the untreated right horn and the control animals (light/no drug and drug/no light). HISTOLOGICAL CHANGES: Following PDT a marked atrophy of the endometrial layer was observed in most animals leaving just a single cell epithelial layer covering the myometrium. SKIN PHOTOSENSITIVITY: None of the animals showed any alterations in the light treated skin area at any time. These promising results show that PDT of the endometrium is possible after topical application of the photosensitising drug and the laser light without provoking skin sensitivity.

Animals↗
PubMed1996

A mathematical model for light dosimetry in photodynamic destruction of human endometrium.

We are involved in the development of photodynamic therapy (PDT) as a minimally invasive method for treating dysfunctional uterine bleeding, one of the primary clinical indications for hysterectomy. In this paper, we analyse light propagation through the uterus in order to specify the requirements for a light delivery system capable of effectively performing endometrial PDT. Our approach involves developing an analytical model based on diffusion theory to predict optical fluence rate distributions when cylindrical and spherical optical applicators are placed in the uterine cavity. We apply the results of our model calculations to estimate the thermal effects of optical irradiation and the effective photodynamic optical dose. Theoretical fluence rate calculations are compared to fluence rate measurements made in fresh, surgically removed human uteri. Our results show that a trifurcated cylindrical optical applicator inserted into the human uterus can provide a light dose that is sufficient to cause photodynamic destruction of the entire endometrium. When the optical power per unit length of each cylindrical applicator is 100 mW cm-1 (at 630 nm), a fluence rate of 40 mW cm-2 is delivered to the boundary layer between the endometrium and the myometrium (a depth of about 4-6 mm). The optical fluence delivered to the boundary layer after 20 min of exposure is 50 J cm-2, a level that is generally accepted to cause tissue damage throughout the endometrium in most patients.

Dose-Response Relationship, Radiation↗
PubMed1996

Regeneration processes in rabbit endometrium: a photodynamic therapy model.

The origin and process of regeneration in rabbit endometrium was evaluated following photodynamic epithelial destruction using topically applied aminolevulinic acid (ALA). Selective destruction of endometrial epithelium was performed using photodynamic therapy (PDT). ALA was diluted to 200 mg/ml dextran 70 shortly prior to administration. A volume of 1.2 ml was injected into the left uterus. Intrauterine illumination (wavelength 630 nm, light dose 40-80 J/cm2) was performed 3 h after drug administration. Tissue morphology was evaluated by light and scanning electron microscopy 1, 3, 7 and 28 days post-treatment (three animals at each time-point). Regeneration of the endometrium following epithelial ablation by PDT was fully activated after 24 h and was completed after 72 h. Endometrial surface generation occurred by proliferation, originating primarily in deeper regions of the glands. Findings from our morphological follow-up study support the origin of endometrial regeneration being mainly from undifferentiated stem cells and residual glandular epithelium.

Aminolevulinic Acid↗
PubMed1995

Photomedicine of the endometrium: experimental concepts.

Gynaecological photomedicine offers new diagnostic and therapeutic methods based on the interaction of light with the reproductive organs. One example is photodynamic therapy (PDT) in which photosensitizers are applied systemically or topically for selective endometrial ablation. Several studies describing the potential use of PDT for this application are reviewed. Basic experimental and clinical aspects of PDT, such as photosensitizer types, application modes, irradiation parameters, optical properties of tissues and photodegradation of photosensitizers are discussed.

Animals↗
PubMed1995

Rat reproductive performance following photodynamic therapy with topically administered Photofrin.

A rat animal model was used for comparing the photodynamic efficacy of two formulations of topically administered Photofrin in the uterus: 0.7 mg/kg Photofrin and 0.7 mg/kg Photofrin + 4% Azone, a penetration-enhancing agent. Uterine structure and reproductive performance were evaluated following illumination with 80 J/cm2 of 630 nm light. Fluorescence microscopy was employed to determine drug localization in frozen uterine sections at various times after drug administration. Functionality studies demonstrated a significant reduction in the number of implantations per treated uterine horn compared to controls. The mean number of implantations decreased systematically on increasing the interval between Photofrin administration and light application. At 72 h, 0.88 +/- 0.52 gestational sacs per rat were recorded with Photofrin therapy, compared with 8.1 +/- 1.12 (P = 0.01) on the untreated side, indicating nearly complete loss of reproductive capability. Similar results were achieved after only 3 h treatment with Photofrin + Azone (0.38 +/- 0.26 sacs per rat versus 7.5 +/- 1.07 on the untreated side; P = 0.01). This indicates that the effect of Photofrin can be enhanced either by extending the drug incubation period from 3 to 72 h or by adding the penetration-enhancing drug Azone. Fluorescence pharmacokinetic studies suggest that both forms of topically administered Photofrin are diffusely distributed throughout the endometrium at virtually the same rate. However, Azone may enhance the selectivity of photodynamic therapy by facilitating drug targeting to critical endometrial structures.

Administration, Topical↗
PubMed1995

Generation of RAPD-PCR primers for the identification of isolates of Glomus mosseae, an arbuscular mycorrhizal fungus.

Mycorrhizal fungi are usually identified on the basis of the morphological characters shown by fruit bodies, spores, vegetative mycelia or symbiotic structures. The development of molecular techniques provides a valuable and alternative approach to identify mycorrhizal fungi, especially when it is difficult to gather a sufficient number of data on morphological features. Short arbitrary oligonucleotides were used as primers for the amplification of genomic DNA extracted from spores of arbuscular fungi. The RAPD fingerprints showed banding patterns which allowed us to distinguish between species and even isolates within Glomales. In order to identify mycorrhizal fungi during their symbiotic phase, a nonpolymorphic RAPD band identified as marker for some isolates of Glomus mosseae was purified from agarose gels and cloned in a bluescript vector. The fragment was sequenced and specific primers (PO-M3) were designed for the mycorrhizal fungus. They specifically and successfully amplified the DNA not only from G. mosseae spores, but also from roots of pea, clover, leek and onion plants when they were colonized by G. mosseae isolates.

Base Sequence↗
PubMed1994

Photodynamic destruction of endometrial tissue with topical 5-aminolevulinic acid in rats and rabbits.

OBJECTIVE: The goal of this study was to determine the optimal parameters for photodynamic endometrial destruction with topically applied 5-aminolevulinic acid, a precursor for the endogenous synthesis of the fluorescent photosensitizer protoporphyrin IX. STUDY DESIGN: 5-Aminolevulinic acid pharmacokinetics were measured in rat and rabbit models by analyzing tissue frozen sections 3 to 12 hours after topical administration. Dose-response studies were conducted for 100 to 400 mg/ml 5-aminolevulinic acid. Photodynamic therapy was performed intraluminally, and tissue morphologic features were evaluated 3 and 7 days after treatment. RESULTS: Peak fluorescence was observed 3 hours after topical administration. Glandular fluorescence significantly exceeded stromal and myometrial in all studies, particularly for 200 mg/ml 5-aminolevulinic acid. Histologic studies revealed persistent epithelial destruction with minimal regeneration. CONCLUSION: Topical 5-aminolevulinic acid photodynamic therapy can be used for highly effective, long-lasting destruction of endometrial epithelium. However, optical dosimetry can vary, particularly in the rabbit model, and this appears to have an impact on long-term reepithelialization.

Administration, Topical↗
PubMed1994

[Unilateral, sensorimotor femoral nerve paralysis following abdominal gynecological operation].

Unilateral or bilateral femoral nerve functional deficiency deficit occurs as a rare iatrogenic complication of gynaecological abdominal or vaginal surgery. Self-retaining abdominal retractors, that exert a constant pressure on the femoral nerve during the operation, are the most frequent cause. This situation occurs especially, if retractors of unsuitable size are used on very slender patients with thin abdominal walls. The favourable prognosis of the femoral nerve sensory and motor deficiencies can be complicated by damage to the knee joint resulting from leg muscle paresis. A personal observation and a literary review on sensomotor paresis after gynaecological abdominal surgery are discussed.

Adult↗
PubMed1994

Determination of the optical properties of the human uterus using frequency-domain photon migration and steady-state techniques.

The optical properties (absorption and transport scattering coefficients) of freshly excised, bulk human uterine tissues were measured at 630 nm using frequency-domain and steady-state photon migration techniques. Measurements were made on both normal (pre- and post-menopausal) and non-neoplastic fibrotic tissues. The absorption coefficient of normal post-menopausal tissue (approximately 0.06 mm(-1)) was found to be significantly greater than that of normal pre-menopausal tissue (0.02-0.03 mm(-1)) and pre-menopausal fibrotic tissue (0.008 mm(-1)). The transport scattering coefficient was similar in all three tissue types considered (0.6-0.9 mm(-1)). From the preliminary results presented here, we conclude that optical properties can be reliably calculated either from the frequency-dependent behaviour of diffusely propagating photon density waves or by combining the frequency-independent photon density wave phase velocity with steady-state light penetration depth measurements. Instrument bandwidth and tissue absorption relaxation time ultimately determine the useful frequency range necessary for frequency-domain photon migration (FDPM) measurements. Based on the optical properties measured in this study, we estimate that non-invasive FDPM measurements of normal uterine tissue require modulation frequencies in excess of 350 MHz.

Algorithms↗
PubMed1994

Relevance of the miscarriage-new pregnancy interval.

There is a wide divergence of opinion concerning the interval a woman should wait after a miscarriage before attempting a new pregnancy ("pregnancy interval"). Many authors recommend waiting 3-4 months in order to reduce the risk of another miscarriage [3, 6, 17, 21]. This retrospective study investigated whether a longer pregnancy interval lowers the risk of repeat miscarriage (R-risk) and/or prematurity. The association between parity and R-risk was also analyzed. Results showed that there are no proven reasons to recommend a waiting period between a miscarriage and a subsequent pregnancy, because the R-risk was around 20% irrespective of interval duration. Prematurity too is not influenced by a waiting period after miscarriage. There was, however, an association between parity and R-risk and risk of prematurity: nulliparae were more likely to have a repeat miscarriage (p < 0.05) or a preterm delivery in the next pregnancy (p < 0.05) than women who had already given birth to a child.

Abortion, Spontaneous↗
PubMed1994

Benzoporphyrin derivative: a potent photosensitizer for photodynamic destruction of rabbit endometrium.

OBJECTIVES: To determine the optimal pharmacokinetic characteristics for photodynamic endometrial destruction using topically applied benzoporphyrin derivative and to evaluate long-term morphologic effects in a rabbit model. METHODS: Benzoporphyrin derivative pharmacokinetics were measured by analyzing frozen tissue sections 1.5-12 hours following topical administration. Photodynamic therapy was induced intraluminally 1.5 hours after drug application, and tissue morphology was evaluated by light and scanning electron microscopy 1 and 4 weeks after treatment. RESULTS: The highest glandular and stromal fluorescence was observed 1.5 hours after topical administration. Relative fluorescence of the endometrial glands significantly exceeded that of stroma and myometrium mainly at 1.5 and 3 hours (P < .0001). Histology revealed persistent epithelial destruction with minimal regeneration. Stroma resembled scar tissue in the majority of sections. The bordering myometrium was loosened and invaded by connective tissue. CONCLUSION: Topically applied benzoporphyrin derivative can be used for highly effective, long-lasting photodynamic destruction of rabbit endometrium. However, optical dosimetry can vary, particularly in the rabbit model, and this appears to affect long-term reepithelialization.

Administration, Topical↗
PubMed1993

DNA probes for identification of the ectomycorrhizal fungus Tuber magnatum Pico.

The random amplified polymorphic DNA (RAPD) technique was used to develop DNA probes for the identification of ectomycorrhizal fungi belonging to the genus Tuber. RAPD fingerprinting revealed a high degree of interspecific variability and a low degree of intraspecific variability. One band (approximately 1.5 kb), consistently appearing when genomic DNA was amplified with an aspecific primer (OPA-18), was found to be a good marker for Tuber magnatum, and was used as a probe in Southern hybridization experiments. The specificity of the results suggests that this probe may be useful in developing specific primers for PCR amplifications.

Ascomycota↗