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Biomedical subjects

F E Kruse

Publications and source records attributed to F E Kruse.

At least 73 records · Page 4Linked to original sources

[Devitalization of lens epithelium cells by dye-enhanced therapy].

UNLABELLED: Hitherto secondary cataract has been usually treated by Nd:YAG laser, which results in a dissection of the capsule with possible complications e.g. retinal detachment. Selective removal of the epithelial cells from the posterior capsule has not been possible. By use of dyes in connection with laser light of a suitable wavelength, lens epithelial cells could potentially be selectively destroyed. We investigated the dye indocyanine green, which has a peak absorbtion at the emission wavelength of commercially available diode lasers. METHODS: Human lens epithelial cells and 3T3 cells (mouse embryonal fibroblasts) were grown in MEM with 10% FBS. Confluent and preconfluent layers were incubated with indocyanine green and treated with a diode laser attached to a slit lamp (810 nm, Zeiss VISULAS, Zeiss Oberkochen, Germany). RESULTS: Indocyanine green alone was toxic in concentrations above 5 mg/ml (60 min). Combined with laser treatment (200 mW, 100 ms, 160 microns), indocyanine green led to cell damage in preconfluent cultures at concentrations above 0.01 mg/ml (10 min). After about 2 days irradiated cells became necrotic and began to desquamate from the culture disc. Cells in confluent cultures could be devitalised at concentrations above 0.05 mg/ml (10 min) using the same power. In contrast, neither indocyanine green alone nor diode laser alone could interfere with epithelial proliferation. DISCUSSION: The experiments show the possibility of dye-enhanced therapy of lens epithelial cells with indocyanine green and diode laser. In contrast to other photosensitizers, indocyanine green is widely used in human function tests. Therefore its use for the treatment of secondary cataracts may merit discussion.

Cell Division↗

[Diagnosis and and differentiation of dry eye disorders].

Artificial tears often fail in dry eye patients. Our goal was to establish a diagnostic approach that involves alternatives that are more effective for the treatment. We examined 110 patients with dry eyes not stabilized by artificial tears: medical history, visual acuity, slit lamp examination, rose bengal stains and fluorescein stains, Schirmer test, break-up time (BUT), dye tests, impression cytology, and lid transillumination. This allowed disturbances of the three layers of the tear film (lipid, aqueous, mucin) to be differentiated. Cellular damage of the ocular surface was evaluated and scored by slit lamp examination, rose bengal staining, and impression cytology. Only 8% of the patients with "sicca syndrome" had exclusive aqueous deficiencies amenable to artificial tears. In contrast, lipid deficiencies (chronic blepharitis) were determined most frequently (78%). Twenty-six percent had disturbances in two or more layers of the tear film. The diagnostic strategy of differentiating disturbances of the layers of the tear film offers a more specific approach to the treatment of dry eyes.

Adult↗

[Fluconazole level in aqueous humor after oral drug administration in humans].

For 2 years fluconazole, a triazole antimycotic, has been available for treatment of systemic mycosis. Compared to amphotericin B fewer severe side effects have been reported. So far, no data have been published as to its penetration into the human eye. In the present study, 20 cataract patients were given 200 mg fluconazole (0.5 to 8 h preoperatively. During the cataract operation 0.1 ml of the aqueous was removed as well as 10 ml serum. With the help of high-pressure liquid chromatography (HPLC), the concentration of fluconazole in each of the samples was determine. If the aqueous humor was removed at least 2h after fluconazole application, concentrations between 2.7 and 5.4 micrograms/ml were reached (mean 3.7 +/- 2.17) In these cases the concentration in the aqueous humor was 80% of the concentration found in the serum at the same time. If the sample of the aqueous humor was collected only 1 h after application, 40% of the concentration in the serum was found in the aqueous humor. These data prove that fluconazole shows an extremely good penetration through the blood-aqueous barrier. After a single dose of 200 mg, a concentration is reached in the eye that surmounts the minimal inhibiting concentration found for Candida species sensitive to fluconazole. Therefore, fluconazole seems to be a good alternative to amphotericin B for the treatment of infections caused by such fungi.

Administration, Oral↗

[Comparison between local and systemic administration of cyclosporin A on the effective level in conjunctiva, aqueous humor and serum].

Cyclosporine is an important tool for the therapy of immunological diseases of the cornea and conjunctiva, as well as the treatment of patients with high-risk corneal grafts. However, potentially severe systemic side effects are disadvantageous. The purpose of our study was to determine if topical ocular application leads to about the same concentrations in ocular tissues as systemic application. Therefore, the concentration of cyclosporine in conjunctiva, aqueous humor and blood was measured by radioimmunoassay in six patients with systemic administration of cyclosporine and ten patients who received one drop of topical cyclosporine 2% four times prior to cataract surgery. All patients with systemic application showed measurable concentrations of cyclosporine in blood, as did four patients in the group receiving topical cyclosporine. There was no significant difference between both groups concerning cyclosporine concentration in aqueous humor. The level of cyclosporine in the conjunctiva was significantly higher after topical application (P < 0.02). In conclusion, therapy with cyclosporine eye drops results in levels in the conjunctiva and aqueous humor that are comparable to or even higher than those after systemic application if the last application was no more than 18h prior to the measurement. Therefore, topical ocular application of cyclosporine, which reduces or eliminates the drug's systemic side effects, can be used to induce local immunosuppressive activity, particularly in the treatment of superficial immunological diseases and after limbal allograft transplantation.

Administration, Oral↗

Reproducibility of the optic nerve head topography with a new laser tomographic scanning device.

BACKGROUND: Laser scanning tomography has been shown to be an accurate and reliable method for the assessment of the three-dimensional optic disc topography. The authors investigate the reliability of morphometric measurements with the Heidelberg retina tomograph, a new instrument which was designed based on this technology, which simplifies handling and is much smaller than the laser tomographic scanner. METHODS: Three independent measurements of the optic disc were performed in 39 eyes of 39 patients which were equally divided into the following three groups: glaucoma, glaucoma suspects, and controls. RESULTS: The mean coefficient of variation for measurement in the glaucoma, glaucoma suspect, and control groups was 2.9%, 5.0%, and 3.4%, respectively, for cup area; 4.9%, 4.6%, and 4.6%, respectively, for cup volume; 5.2%, 3.8% and 3.3%, respectively, for mean cup depth; and 5.2%, 4.1%, and 4.0%, respectively, for maximal cup depth. The mean standard deviation for one pixel of the total image was 30 +/- 6 microns, 28 +/- 7 microns, and 22 +/- 6 microns for the three groups, respectively. CONCLUSION: The Heidelberg retina tomograph enables fast and reliable measurement of the optic disc topography and therefore may allow exact follow-up of patients.

Adult↗

Stem cells and corneal epithelial regeneration.

Self-renewing tissues such as the corneal epithelium contain stem cells which represent the proliferative reserve. Studies of cellular differentiation and proliferation suggest that corneal epithelial stem cells are localised exclusively in the basal limbal epithelium. Although regulatory factors for the amplification of corneal stem cells are unknown, serum factors such as retinoic acid might induce differentiation of stem cells to transient amplifying cells which are responsible for cell amplification. These cells are regulated by various polypeptide growth factors and extracellular calcium. Loss or malfunction of stem cells does not permit maintenance or regeneration of the corneal epithelial mass but leads to conjunctivalisation of the corneal surface. Clinically, several ocular surface disorders such as chemical burns can cause limbal damage and consecutive limbal insufficiency. Treatment for these disorders is available only by transplantation of healthy stem cells, which can be performed as both autograft and allograft.

Cell Differentiation↗

[Therapy of dry eye disorders].

BACKGROUND: The treatment of dry eyes with artificial tears often fails. We differentiated the disturbances of the three layers of the tear film in 90 such patients. This showed that only 11.1% had aqueous deficiency, while 42.3% had combined disturbances of different layers of the tear film, and 76.7% had lipid deficiencies. PATIENTS AND METHODS: We now studied the efficacy of a therapeutic approach, which intended to stabilize each individual deficiency of the three layers of the tear film (follow-up > or = 6 months). The medical history, visual acuity, slit lamp examination, rose bengal stains and fluorescein stains, Schirmer test, break-up time (BUT), dye tests, impression cytology, and lid transillumination were analyzed. RESULTS: Therapy was beneficial in all patients (n = 90) with regard to the symptoms and the objective parameters. Artificial tears applied strictly were without preservatives. Patients with toxic conjunctivitis induced by high dosages of eye drops were often stabilized through withdrawing the medication. The frequency of applying artificial tears was significantly tapered by punctum plugs and -coagulation. Tarsorrhapies were helpful in the most severe cases. Topical retinoids significantly reduced the symptoms and increased the goblet cell density. Treating chronic blepharitis was very sufficient, when initiated by topical steroids and Tetracycline, and systemical Doxycycline. CONCLUSIONS: Differentiating the disturbances of the three tear film layers in "sicca syndrome", and stabilizing each component is more effective than artificial tears alone.

Combined Modality Therapy↗

Retinoic acid regulates clonal growth and differentiation of cultured limbal and peripheral corneal epithelium.

PURPOSE: To determine if vitamin A could be one of the factors in serum responsible for the previously observed effect of 20% fetal bovine serum on stimulating clonal growth of an additional subpopulation in limbal cultures, possibly stem cells, but inhibiting that of transient amplifying cells in peripheral corneal cultures. METHODS: A reported serum-free clonal growth assay was used. The mitogenic response was measured by colony-forming efficiency (CFE), colony size, and BrdU labeling index; the differentiation was assessed by colony morphology, AE-5 monoclonal antibody staining, and cornified envelope formation. RESULTS: HPLC analyses revealed that added retinoic acid (RA) was rapidly taken up by cultured cells. As compared to the control without RA, low concentrations of RA (10(-9) M to 10(-7) M) stimulated the CFE of limbal cultures but did not change that of peripheral corneal cultures. Furthermore, 10(-8) M RA induced the emergence of two new types of colonies, one of which was almost exclusively present in limbal cultures, and allowed continuous clonal growth of some colonies in late limbal cultures. RA also dose dependently reduced colony size and BrdU labeling index in both limbal and peripheral corneal cultures. RA in concentrations above 10(-8) M stimulated normal differentiation of both limbal and peripheral corneal epithelial cells, as evidenced by increased AE-5 staining, but inhibited the formation of cornified envelopes, an index for abnormal, squamous metaplasia, in late cultures. CONCLUSION: These results suggest that RA has a differential dose-dependent effect on subpopulations of corneal and limbal epithelial cells. Although RA stimulates the conversion of limbal stem cells to transient amplifying cells, it inhibits the amplification of corneal and limbal transient amplifying cells and prevents abnormal terminal differentiation. These data further support the role of vitamin A as a physiological modulator of proliferation and differentiation of the ocular surface epithelium.

Animals↗

[Transforming growth factors beta 1 and 2 inhibit proliferation of limbus and corneal epithelium].

The role of the various isoforms of transforming growth factor-beta (TGF-beta) concerning the regulation of proliferation, differentiation and wound healing of the corneal epithelium is controversial. We investigated various concentrations of TGF-beta 1 and 2 in a serum-free, defined clonal growth assay concerning the proliferation of limbal and peripheral corneal epithelium. Concentrations between 0.05 and 5.0 ng/ml of either TGF-beta 1 or 2 caused a significant, dose-dependent decrease of both colony formation and colony proliferation in limbal and peripheral corneal epithelial cultures. These results suggest a physiological role for TGF-beta as a negative growth regulator targeting primarily the transient amplifying cells of the limbal and corneal epithelium.

Animals↗

[Coats syndrome in retinitis pigmentosa. Clinical aspects and therapeutic possibilities].

Coats disease itself is a rather rare condition, whereas Coats syndrome has been observed in about 1.2-4.9% of all retinitis pigmentosa (RP) patients. The spectrum of clinical presentations and our therapeutic experience are illustrated with reference to case reports of three patients with clinically and electrophysiologically verified RP and Coats syndrome. As in classic Coats disease, Coats-like changes with RP are defined by aneurysmatic and teleangiectatic vessels and intra- and subretinal lipid deposits leading to exudative retinal detachment. Both entities differ with regard to age of onset, gender, bilaterality and location of the retinal changes. The reports published up to now show that there is no consensus concerning the success of the different treatments of Coats syndrome associated with RP. Laser therapy, cryocoagulation, diathermy and buckling procedures have been suggested for treatment of this complex. As in the therapy of Coats disease, our results confirm that the outcome of laser therapy depends on early detection of Coats-type vascular abnormalities and early initiation of the treatment. Therefore, thorough fundus examination should be regularly performed in all RP patients.

Adolescent↗

[Prognosis of intralenticular lead foreign bodies].

BACKGROUND: The prognosis of intraocular foreign bodies consisting of lead remains controversial. While experiments have shown that infected lead becomes sterile when fired from rifles, both the total absence as well as presence of severe inflammation have been observed following perforating injuries with lead. Furthermore, alterations of the ERG have been described in experimental settings. This case report is presented in order to clarify the long term prognosis of intralenticular lead particles. PATIENT AND METHOD: The 69-year-old patient suffered from a bilateral perforating injury caused by a bullet during World War II (1942). The right lens was extracted due to a secondary cataract several weeks following the injury. The left lens remained clear despite a paracentrally located metallic foreign body. The patient underwent extracapsular cataract extraction in 1992 because of an opacity of the posterior capsule which was well separated from the foreign body. Preoperatively the ERG was normal. An energy dispersive X-ray microanalysis in a scanning electron microscope was performed in order to determine the chemical composition of the foreign body, and X-ray diffraction with a Gandolphi camera was used for its structural characterisation. The foreign body consists of lead. However, its surface is probably altered to lead oxide, hydroxide or carbonate, which hindered further reaction of the lead. Calcium phosphate was deposited on the walls of the foreign body. CONCLUSION: Our report shows that lead in the lens remains inert for several decades and does not cause alterations in the ERG. Therefore, intralenticular lead outside of the optical axis may be left in situ unless a secondary cataract develops.

Aged↗

[Determination of retinal nerve fiber density in vivo using laser polarimetry].

BACKGROUND: A direct in vivo measurement of the retinal nerve fiber layer thickness enables new possibilities for the detection of nerve fiber defects. Using the principle of polarimetry the Nerve Fiber Analyzer has been told to measure directly the nerve fiber layer thickness in vivo. PATIENTS AND METHODS: We measured the nerve fiber layer thickness along a peripapillary circle and investigated the reproducibility in 10 independent measurements of 10 left eyes of ten normals. RESULTS: The nerve fiber layer thickness measurements varied between 10 and 130 microns for single pixel measurements. The coefficient of variation was 11.9 +/- 2.6 percent for a peripapillary circle while the temporal, nasal, superior and inferior quandrants were 19.2 +/- 3.6%, 19.5 +/- 4.7, 14.3 +/- 5.6 and 16.4 +/- 5.5 percent, respectively. Mean coefficient of variation in 10 time evaluation of 5 single examinations of 5 different eyes was 1.8 +/- 1.1%. CONCLUSIONS: The first investigations demonstrate a good reproducibility of the measurements observed by the Nerve Fiber Analyzer. Supplementary to three-dimensional optic disc topography and perimetry, nerve fiber layer thickness assessment may become an additional tool for diagnosis and follow-up of early glaucoma. The option of measuring along circle segments or areas instead a peripapillary circle consisting of a single pixel would increase the clinical value and reproducibility. Further studies are warranted to evaluate the accuracy of this new method of polarimetry.

Equipment Design↗

[Bilateral choroid osteoma].

BACKGROUND: Choroidal Osteoma is a rare, typically monolateral benign ossifying tumor of the choroid found in healthy females aged 10 to 30 years. In contrast, multiple idiopathic sclerochoroidal calcifications occur in elderly otherwise healthy subjects. Local or generalized distortions of calcium phosphate metabolism may cause secondary choroidal calcifications. PATIENT: We report on a 56-year-old woman, who underwent removal of a histologically verified osteoma 2 years ago. Ophthalmoscopically, there were multiple prominent choroidal tumors in the inferior midperiphery of both eyes. Ultrasonography showed high reflectivity and marked shadowing posterior to the lesion. CT-scan demonstrated the presence of calcifications. The patient neither belonged to the age group, in which choroidal osteomas are typically found, nor were the lesions located in the typical manner as reported in literature. The location in the inferior choroid has not yet been described for idiopathic sclerochoroidal calcifications. The presence of secondary choroidal calcifications was very unlikely, as there was no history of ocular inflammation or systemic disease such as hyperparathyreoidism or chronic renal failure. CONCLUSION: Thus, despite the lack of histologic examination, one may assume the rare incidence of bilateral choroidal osteomas in atypical inferior localisation in our patient.

Choroid↗

A tumor promoter-resistant subpopulation of progenitor cells is larger in limbal epithelium than in corneal epithelium.

PURPOSE: In the epidermis, proliferative basal cells can be divided into two subpopulations according to their response to phorbol ester tumor promoters. The tumor promoter-sensitive subpopulation ceases mitosis and initiates terminal differentiation and, thus, represents more differentiated transient amplifying cells. In contrast, the tumor promoter-resistant subpopulation that continues to proliferate may be the target of neoplastic transformation by chemical carcinogens and may contain stem cells. Based on this concept, we examined the differential response of stem cell-containing limbal epithelium and transient amplifying cell-containing corneal epithelium to phorbol 12-myristate 13-acetate (PMA) treatment. METHODS: A reported serum-free clonal growth assay was used. The mitogenic response was measured by colony-forming efficiency (CFE), colony size, bromodeoxyuridine (BrdU) labeling index; the differentiation was assessed by colony morphology, AE-5 monoclonal antibody staining. RESULTS: The addition of PMA dose dependently inhibited the clonal proliferation of both limbal and corneal epithelial cultures with respect to CFE, colony size, and BrdU labeling index, suggesting that both cultures contain PMA-sensitive subpopulations. Nevertheless, the magnitudes of a decrease in CFE and colony size in peripheral corneal cultures were significantly greater than those in limbal cultures, indicating that the size of the PMA-resistant subpopulation is larger in the limbal epithelium. The inhibitory effect of PMA on clonal proliferation was partially reversible upon its early withdrawal, indicating that its inhibitory effect is continuous and coupled with progressive differentiation of progenitor cells in this culture system. CONCLUSION: These results further suggest that the cell cycle length of progenitor cells correlates with the mitogenic pathway mediated via calcium- and phospholipid-dependent protein kinase C, the receptor inhibited by prolonged treatment of phorbol ester tumor promoters.

Animals↗

Serum differentially modulates the clonal growth and differentiation of cultured limbal and corneal epithelium.

PURPOSE: The stem cell-containing limbal epithelium is in proximity with highly vascularized tissue, as opposed to the transient amplifying cell-containing corneal basal epithelium, which resides on top of avascular corneal stroma. We therefore speculate that limbal stem cells are preferentially under the modulation of serum-derived factors. METHODS: Using a previously reported serum-free, chemically defined culture system for ocular surface epithelium, a culture condition primarily supporting transient amplifying cells of both corneal and limbal epithelia, we compared the clonal growth measured by colony-forming efficiency (CFE), colony size, and BrdU labeling, as well as colony differentiation measured by colony morphology and immunofluorescence staining, with the monoclonal antibody AE-5 against keratin K3 when fetal bovine serum (FBS) was added at different concentrations. RESULTS: The addition of 1% FBS decreased CFE and colony size in peripheral corneal cultures but had no effect in limbal cultures. Both cultures showed no obvious difference in colony morphology or BrdU labeling and AE-5 staining. In contrast, at 10% or 20% FBS, CFE and colony size increased in limbal cultures, but dose dependently decreased in peripheral corneal cultures. The presence of a unique subpopulation of progenitor cells in limbal cultures different from transient amplifying cells in corneal cultures was further supported by the emergence of a higher proportion of a unique type (B) colonies in limbal cultures that had high BrdU labeling and heterogeneous or negative AE-5 staining, indicative of their being in a proliferating, undifferentiated state. These colonies showed continuous growth in late cultures and could be passaged into serum-free medium. CONCLUSION: These results indicate that serum contains factors responsible for stimulating limbal progenitor cells into clonal proliferation.

Animals↗

[Goniotrepanation combined with sinus surgery as a transitional measure in spontaneous carotid artery-cavernous sinus fistulas].

Two patients with spontaneous, angiographically proven fistulas showed progressive ocular symptoms which precluded waiting for spontaneous occlusion of the fistulas. On the other hand, endovascular therapy of the carotid-cavernous fistulas was not possible because the arterial supply of the fistulas came from both internal carotids. Therefore filtering surgery was performed in the affected eyes. Postoperatively, intraocular pressure decreased to normal values in both patients and the symptoms resolved. The visual acuity increased in one patient and remained the same in the other. In conclusion, filtering surgery is an important therapeutic tool to preserve visual function in eyes with carotid-cavernous fistulas that display progressive ocular symptoms but cannot be treated by embolization.

Aged↗

[Retinoic acid inhibits the proliferation of dividing cells in peripheral corneal epithelium].

The regulation of proliferation of transient amplifying cells from the corneal epithelium by all-trans-retinoic acid was investigated by means of a serum-free clonal growth assay. While retinoic acid did not alter cell attachment, a dose-dependent and significant inhibition of both colony formation and clonal proliferation was observed. The data indicate that retinoic acid inhibits the proliferation of corneal transient amplifying cells. Therefore, retinoic acid might also play a role in regulating the proliferation of the corneal epithelium in vitro.

Cell Differentiation↗

[Differing regulation of proliferation of limbus and corneal epithelium caused by serum factors].

The basal limbal epithelium contains corneal stem cells, which are responsible for the maintenance of the corneal epithelial mass. In our study of the regulation of limbal progenitor cells, we investigated the proliferation of limbal and corneal epithelial cells in a defined single-cell clonal culture system. In a serum-free defined medium the limbal epithelium generated significantly fewer colonies than the cornea, which also proliferated more slowly. The addition of fetal calf serum resulted in the stimulation of a unique subpopulation of progenitor cells at the limbus. In contrast, proliferation of the peripheral corneal epithelium was inhibited by serum. These results further support the concept of a limbal location of corneal stem cells and suggest that limbal progenitor cells might be regulated preferentially by serum factors.

Cell Count↗