PubMed Health⌕ Search

Biomedical subjects

W Fink

Publications and source records attributed to W Fink.

At least 19 recordsLinked to original sources

Clinical phase II study of pegylated liposomal doxorubicin as second-line treatment in disseminated melanoma.

BACKGROUND: Stage IV melanoma has a poor prognosis with a median survival of 3-11 months from diagnosis of distant metastases. Response rates in first-line regimens range around 15-20%. Non-responders have a median survival around 6 months. Currently, no second-line treatment in advanced melanoma has been established. PATIENTS AND METHODS: In a clinical phase II study we evaluated the efficacy of liposomal doxorubicin (Caelyx) in 30 patients (17 m, 13 f) with progressing metastatic melanoma who had failed a previous chemotherapy. Liposomal doxorubicin was given in an outpatient setting at a dose of 50 mg/m2 i.v. on d1, d22, d43 and d64, subsequently at 40 mg/m2 at d85 before first staging and in 4-week intervals thereafter. Treatment was very well tolerated with 100 cycles given in total. Response rate, survival time, time-to-progression and toxicity were assessed. RESULTS: Erythrodysesthesia was the most severe toxicity in 6% at CTC grade 3. Liposomal doxorubicin was of limited clinical efficacy with 21 patients progressing within the first 12 weeks. However, 7 patients were treated 3-9 months and were stable for >90 days, achieving 5 SD, 1 PR and 1 CR. Median survival after initiation of second-line treatment was 214 days (95% CI: 151-304 days) with 7 patients surviving >300 and 5 patients >400 days. CONCLUSIONS: Liposomal doxorubin as monotherapy is well tolerated but of limited clinical efficacy. Whether the survival benefit of a significant proportion of patients (20%) holds true in larger cohorts and whether the efficacy of liposomal doxorubicin can be improved by combinations without compromising the low toxicity profile needs further studies.

Adult↗

Mucosal metastases in malignant melanoma.

BACKGROUND: We present the case of a patient with malignant melanoma stage IV according to the American Joint Committee on Cancer (AJCC) classification and an unusual pattern of metastasis to the mucosa of the esophagus, the stomach, the bladder and the palatine tonsil. CASE REPORT: A 38-year-old male patient with metastatic malignant melanoma of stage III (AJCC) was admitted for initiation of adjuvant therapy. 4 months earlier a primary melanoma of the left upper leg had been excised and 2 months later the patient had undergone a left inguinal lymph node dissection revealing 2 metastatic lymph nodes. On admission the patient complained of a sore throat and right cervical lymphadenopathy. He underwent a tonsillectomy and a lymphadenectomy which both revealed melanoma metastases. A PET scan using F-18-fluorodeoxyglucose (FDG) showed focal metabolic activity in the middle mediastinum. Two cycles of dacarbazine (DTIC) chemotherapy were performed during which the patient developed cutaneous metastases, dyspepsia, and mild hematemesis. Gastroscopy revealed bleeding from mucosal metastases of the esophagus and stomach. A few weeks later the patient developed macroscopic hematuria. A cystoscopy was performed and showed metastases to the mucosa of the bladder. Nutrient vessels of these bladder metastases were embolized in order to control bleeding. The patient is currently alive with progressive disease. RESULTS: This case presents common and uncommon sites of metastatic melanoma to the mucosa with the typical clinical manifestations in a single patient.

Adult↗

[Renaissance of general practice].

Special research work has taught that general practice (family medicine) is a specialization of its own. It requires specific education and vocational training. As far as universities and administrative bodies have accepted it no doctor can start practising family medicine unless he has passed a vocational training of many years duration. That fact together with a successful continued research concerning applied general practice should initiate a true renaissance of general practice.

Austria↗

Beam-deflection method of diagnosing impaired vision.

We describe a simple method to assign a diagnosis of cataract to patients with obscurely impaired vision as well as to those with mild lens opacities. When the narrowest slit is used in a slitlamp examination, a small beam of light appears on the macula. Routine fundoscopy with the 78.0 diopter lens or a 3-mirror glass is appropriate. If a cataract is present, the beam of light is scattered into several straight lines, distorted lines, or both. This has proved a useful diagnostic tool when the lens appears clear but the patient's vision is impaired, and extensive examinations such as computer tomography or nuclear magnetic resonance tomography for impaired vision may be avoided. The beam-deflection method uses devices that are generally available and can detect cataract in the early stages of development.

Adolescent↗

Efficacy of mifepristone followed on the same day by misoprostol for early termination of pregnancy: report of a randomised trial.

OBJECTIVE: To examine the clinical efficacy of mifepristone 600 mg followed on the same day or two days later by misoprostol 400 microg orally in women undergoing medical termination of pregnancy whose pregnancies have a gestational age up to 49 days. DESIGN: Prospective, randomised trial. SETTING: Clinical research office. PARTICIPANTS: Eighty-six women, requesting elective termination of a pregnancy which has a gestational age of < or = 49 days. METHODS: After administration of mifepristone 600 mg, participants were randomised to take misoprostol six to eight hours later (Group 1) or 48 hours later (Group 2). Women returned for a follow up evaluation 24 +/- 1 hours after taking the misoprostol. Participants in Group 1 who had not aborted received a second dose of misoprostol to take 48 hours after the mifepristone. All women returned approximately two weeks after receiving mifepristone. If termination of pregnancy had still not occurred and the pregnancy was non-viable, the woman returned again in three weeks. MAIN OUTCOME MEASURES: Rate of complete abortion 24 hours after administration of misoprostol. RESULTS: At 24 hours after receiving misoprostol, 21/42 (50%, 95% CI 35%, 65%) women in Group I and 40/44 (91%, 95% CI 82%, 99%) women in Group 2 had complete abortions. By follow up two weeks later after the administration of mifepristone, 40/42 (95%, 95% CI 89%, 100%) women in Group 1 and 43/44 (98%, 95% CI 93%, 99%) women in Group 2 were known to have complete abortions. Nausea, vomiting or diarrhoea in women using the standard regimen (Group 2) occurred in 68%, 36%, and 20%, respectively. CONCLUSIONS: After treatment with mifepristone 600 mg, administration of misoprostol 400 microg orally on the same day is not as effective at causing abortion within the first 24 hours compared with the standard time interval of 48 hours between medications.

Abortifacient Agents, Nonsteroidal↗

Immunohistochemical and molecular characterization of cultured keratinocytes after dispase-mediated detachment from the growth substratum.

Keratinocyte activation comprises changes in protein and gene expression pattern resulting in phenotypic and functional changes necessary for re-epithelialization such as the expression of urokinase-type plasminogen activator (uPA) and its cell surface receptor (uPA-R; CD87). As uPA and uPA-R are rapidly induced after dispase-mediated detachment of cultured normal human epidermal keratinocytes (NHEK) we hypothesized that dispase-mediated detachment may cause a similar "activation" of keratinocytes with uPA and uPA-R being only one aspect of a complex "activation reaction". To test this hypothesis we have comparatively analysed adherent versus detached keratinocyte sheets for selected indicators of keratinocyte activation by immunohistochemistry. Furthermore we have identified genes via subtraction cloning which are up-regulated upon dispase-induced detachment. The analyses provided evidence for an increased transcriptional and translational activity in detached keratinocytes, as indicated by over-expression of several ribosomal components (L3 and S10 ribosomal protein) and transcription factors (initiation factor 4A, elongation factor 1alpha). Increased proliferative activity was indicated by increased expression of the proliferation markers Ki67, keratin 6 and keratin 17. Finally, several markers of keratinocyte activation such as the integrin chain alpha(v), psoriasin, glutathion-S-transferase and heparin-binding epidermal growth factor-like growth factor were up-regulated. Furthermore mevalonate kinase, a molecule as yet unknown to be expressed in keratinocytes, was identified. The findings provide evidence that dispase-mediated detachment in cultured keratinocytes induces a reaction, which comprises the up-regulation of a complex array of proliferation- and migration-related molecules. The pattern of which resembles the activation reaction observed in the re-epithelializing keratinocytes in vivo.

Biomarkers↗

Electronic Structure of the Aqueous Vanadyl Ion Probed by 9 and 94 GHz EPR and Pulsed ENDOR Spectroscopies and Density Functional Theory Calculations.

The aqueous vanadyl ion ([VO(H(2)O)(5)](2+)) has been investigated by X-band EPR, 94 GHz W-band EPR, and ESE-ENDOR. These experiments reveal information about the hyperfine (|A(xx)| = 208.5 MHz, |A(yy)| = 208.5 MHz, |A(zz)| = 547.0 MHz), and nuclear quadrupole coupling (|e(2)qQ| = 5.6 MHz) of the (51)V nucleus. The measured nuclear quadrupole coupling parameters are compared to values determined by density functional theory calculations (|e(2)qQ| = 5.2 MHz). These theoretical calculations illustrate that axial ligands and molecular distortions can alter the magnitude of the nuclear quadrupole interaction.

Journal Article↗

Scheimpflug records without distortion--a mythos?

The Scheimpflug principle was recommended as allowing distortion-free imaging; however, a detailed analysis reveals geometrical errors as well as distortions arising from absorption of light along the optical pathway. Correction formulas and factors will be presented and applied to the biometry of the eye.

Biometry↗

[Axial displacement of IOL and visual impairment].

BACKGROUND: After a cataract surgery procedure with vitreous loss a vitreous strand remained in the wound. An unusual visual impairment was observed. PATIENT: A shift in refraction depending on the pupillary diameter was observed. In miosis the refraction was estimated to +1.0 sph, in mydriasis -1.0 sph/ -0.5 cyl, respectively. METHOD: We presumed that the vitreous strand between the iris and the intraocular lens caused an axial displacement of the IOL during the change from miosis to mydriasis and v.v. Therefore the vitreous strand was surgically eliminated. After surgery the refractive changes by pupillary actions were overcome. In a computer simulation (ray tracing), the amount of axial displacement of the IOL was estimated to 1.5 mm. CONCLUSION: This paper reminds of considering other reasons for loss of VA than CME, e.g. axial displacement of IOL. An adequate method of examination is the measurement of refraction in miosis and mydriasis.

Aged↗

[R. N. Braun diagnostic programs: what prevents the general practitioner from using them? Results of a 1-year-study of indications, acceptance and failure to apply diagnostic programs].

In General Practice, a global measure for quality control has not yet been established. Procedures in this field of health care are usually not evidence based but rely on personal experience. In 1976, the "Diagnostic Protocols" (DP) had been introduced by Robert N. Braun to cover the most frequent and most important uncharacteristic complaints presented to the General Practitioner by the patient. In this study, the authors are showing how often the usage of DP may be useful in the management of cases in General Practice. Additionally, reasons are demonstrated that may lead the Family Physician not to apply DP in certain cases. In 2,084 new cases presented to a General Practitioner within one year (1-12/1994), 19 of 82 existing protocols were used. In every sixth new case (16%), the patient's history and physical examination were analyzed with the help of Diagnostic Protocols. However, their usage would have been beneficial in one of four cases (24.6%). Reasons for declining DP included "No need for further diagnostic investigation" and "Other diagnostic strategy chosen". Shortness of time only played a minor role.

Attitude of Health Personnel↗

[Visual image in high ametropia. Computer-assisted simulation with optic ray calculation].

PURPOSE: A computer program developed by the authors allows to calculate the path of light rays coming from an object through all the refractive surfaces of a Gullstrand model eye until it reaches the retina. METHOD: The program calculates several hundred light rays for every point of a given object. A menue allows to modify optical and morphological parameters in an interactive way. For instance, the indices of refraction, the radii of the cornea and of the cristalline lens, as well as the length of the bulbus can be modified. Further, one can add seeing aids such as eye glasses or a contact lens, or implant an artificial intraocular lens. The seeing aids may be decentered and/or tilted. RESULTS: The code calculates also the visual impression by projecting the image from the retina back to a screen at the distance of the object, where the human brain "sees" the object. For image interpretation we use a normal Gullstrand eye with a very small aperture stop. In this way we can simulate the visual mapping (visual impression) of a corrected or uncorrected ametropia. CONCLUSIONS: In this paper we present two nontrivial examples: we calculate the regional polyopia ("Bildverdoppelung") and the annular scotoma which appear whenever a high myopia or aphakia are corrected by eye glasses.

Computer Simulation↗

A ray tracer for ophthalmological applications.

Ray tracing with a personal computer allows realistic simulation of optical properties of the human eye. Patterns of point sources are used as objects. The path of light rays is calculated between the point source and the retina for a Gullstrand eye model with improved parameters; the normal eye model has a resolution limit close to the natural resolution limit of the human eye. The image formed on the retina is projected back to a screen at the distance of the object so as to simulate image interpretation by the brain. Refractive errors are modeled by a change in eye parameters and corrected by eyeglasses or/and contact lenses or by an artificial intraocular lens. For optic correction the parameters of seeing aids can be fitted automatically by a least-squares routine. The effect of faulty eye correction on image quality is visualized by using a photograph of a realistic scene as an object.

Aphakia↗

Multi-layered perceptron as a model for the pupillary pathway.

Derived from models of neural networks, a model for the pupillary pathway is introduced that can easily be handled computationally and analytically. To model the binocular pupillary reactions we use a feed-forward network, namely, a multi-layered perception. It is possible to calculate the pupillary reactions analytically as a function of the light stimuli of the retinal hemifields, on the one hand, and the set of neural couplings between the neural layers, on the other. Several lesions, e.g., lesions of the intercalated neurons between the afferent and efferent pupillary pathways, can be simulated within the model and the corresponding pupillary reactions such as anisocoria or relative afferent pupillary defects (RAPD) can be calculated analytically. Due to its neural network structure the model described herein can easily be extended to much more complex pupillary pathways while remaining calculable computationally and analytically.

Humans↗

A comparative study of one-year weight gain among users of medroxyprogesterone acetate, levonorgestrel implants, and oral contraceptives.

With the recent introduction and growing popularity of Depo-Provera Contraceptive Injection, concern about the potential for weight gain during treatment has been raised. The purpose of the present study was to determine whether or not Depo-Provera Contraceptive Injection is associated with greater weight gain, and incidence thereof, than Norplant implants or oral contraceptives. A retrospective chart review of patients seen at a state- and federally-funded clinic was conducted. Fifty women in each treatment group who met the study criteria were identified and included in the study evaluation. Mean one-year weight gain for subjects in each group was as follows: -2.0 pounds in the oral contraceptive group, -1.8 pounds in the Norplant implants group, and +0.1 pounds in the Depo-Provera Contraceptive Injection group. While results among treatment groups differed slightly, no significant weight change occurred in any of the treatment groups.

Adolescent↗

Chitinases and beta-1,3-Glucanases in the Apoplastic Compartment of Oat Leaves (Avena sativa L.).

To isolate chitinases and beta-1,3-glucanases from the intercellular space of oats (Avena sativa L.), primary leaves were infiltrated with buffer and subjected to gentle centrifugation to obtain intercellular washing fluid (IWF). Approximately 5% of the chitinase and 10% of the beta-1,3-glucanase activity of the whole leaf were released. Only small amounts (0.01-0.03%) of the intracellular marker malate-dehydrogenase were released into the IWF during infiltration. Activities of chitinase and beta-1,3-glucanase in the IWF and in the leaf extract were compared by different chromatographic methods. On Sephadex G-75, chitinase appeared as a single peak (M(r) 29.8 kD) both in IWF and homogenate. beta-1,3-Glucanase, however, showed two peaks in the IWF (M(r) 52 and 31.3 kD), whereas the elution pattern of the homogenate showed only one major peak at 22 kD. Chromatofocusing indicated that the IWF contained four chitinases and five beta-1,3-glucanases. The elution pattern of the homogenate and IWF were similar with regard to the elution pH, but the peak intensities were distinctly different. Our results demonstrate that extracellular beta-1,3-glucanases are different from those located intracellularly. Extracellular and intracellular chitinases do not differ in molecular properties, except for one isozyme which seems to be confined to the extracellular space. We suggest that both enzymes might play a special role in pathogenesis during fungal infection.

Journal Article↗