Sorafenib prevents liver fibrosis in a non-alcoholic steatohepatitis (NASH) rodent model

Liver fibrosis occurring as an outcome of non-alcoholic steatohepatitis (NASH) can precede the development of cirrhosis. We investigated the effects of sorafenib in preventing liver fibrosis in a rodent model of NASH. Adult Sprague-Dawley rats were fed a choline-deficient high-fat diet and exposed to diethylnitrosamine for 6 weeks. The NASH group (n=10) received vehicle and the sorafenib group (n=10) received 2.5 mg·kg-1·day-1 by gavage. A control group (n=4) received only standard diet and vehicle. Following treatment, animals were sacrificed and liver tissue was collected for histologic examination, mRNA isolation, and analysis of mitochondrial function. Genes related to fibrosis (MMP9, TIMP1, TIMP2), oxidative stress (HSP60, HSP90, GST), and mitochondrial biogenesis (PGC1α) were evaluated by real-time quantitative polymerase chain reaction (RT-qPCR). Liver mitochondrial oxidation activity was measured by a polarographic method, and cytokines by enzyme-linked immunosorbent assay (ELISA). Sorafenib treatment restored mitochondrial function and reduced collagen deposition by nearly 63% compared to the NASH group. Sorafenib upregulated PGC1α and MMP9 and reduced TIMP1 and TIMP2 mRNA and IL-6 and IL-10 protein expression. There were no differences in HSP60, HSP90 and GST expression. Sorafenib modulated PGC1α expression, improved mitochondrial respiration and prevented collagen deposition. It may, therefore, be useful in the treatment of liver fibrosis in NASH.

[Reduction of astigmatism by arcuate incisions using the femtosecond laser after corneal transplantation]. / Korrektur des Astigmatismus nach Hornhauttransplantation durch bogenförmige Inzisionen mit dem Femtosekundenlaser.

AIM: We examined the effectiveness of arcuate incisions by femtosecond laser treatment for high astigmatism in corneal transplants. BACKGROUND: High astigmatism is a well known complication after corneal transplantation and is difficult to treat. At present, there are many surgical procedures for the correction of high astigmatism after PKP in case of an unsuccessful contact lens therapy. PATIENTS AND METHODS: Ten patients with a high postoperative astigmatism underwent arcuate keratotomy with the Femtec laser. We performed two arcuate incisions on each transplant. With the femtosecond laser technology it is possible to perform precise incisions where the depth and length of the arcus can be programmed. RESULTS: The best corrected visual acuity was improved in eight out of ten patients. The visual acuity of two patients did not change. The average corneal astigmatism was reduced by three dioptres. The average refractive astigmatism was reduced by four dioptres. CONCLUSION: Arcuate incisions with the femtosecond laser on patients with high astigmatism subsequent to corneal transplantation are an effective and safe treatment.

[Transpalpebral tonometry with a digital tonometer in healthy eyes and after penetrating keratoplasty]. / Transpalpebrale Tonometrie mit einem digitalen, tragbaren Tonometer in gesunden Augen und nach perforierender Keratoplastik.

PURPOSE: The Goldmann applanation technique established itself as gold standard for clinical intraocular pressure (IOP) measurement. But the device measures by corneal touch and presupposes corneal conditions within a normal range. So precise determination of IOP is crucial in corneal disorders and after corneal surgery. This pilot study presents tonometry data of normal and postkeratoplasty eyes measured transpalpebrally with a digital tonometer in comparison to Goldmann tonometry. METHOD: The TGDc-01 tonometer is based on a ballistic principle of measurement. IOP was measured in 50 healthy eyes (group 1) and 40 eyes after penetrating keratoplasty (group 2) first by the TGDc-01 and after 3 minutes by Goldmann tonometry (Haag-Streit). Subjective refraction, keratometry and ultrasonic pachymetry were performed in all eyes. The IOP measurements in the postkeratoplasty eyes were done when corneal epithelium was fully closed and only a medium suture edema could be observed. RESULTS: The Pearson's product-moment correlation was r=0,46 for group 1 and 0,65 for group 2. Using the concordance correlation coefficient the value showed a reproducibility index of r(c)=0,44 in group 1 and r(c)=0,60 in group 2. Following the Bland-Altman-analysis 58% of the cases in group 1 had a difference between the two instruments of maximum 3 mmHg. In group 2, 53,5% of the eyes showed an absolute difference between Goldmann and TDGc-01 of 3 mmHg or less. CONCLUSION: A transpalpebral measurement technique-avoiding corneal contact-seems to be an alternative choice in patients with corneal pathologies and after corneal surgery. The TGDc-01 tonometer provided mostly similar results compared to the Goldmann device, but with fluctuations. Keeping the deviations between the two methods in mind we recommend, however, the use of the transpalpebral approach only in combination with other techniques (palpation, indentation) to obtain enough reliability of IOP information in problem eyes.

[SILK--Steroid-induced lamellar keratopathy. A case report]. / SILK-steroidinduzierte lamelläre Keratopathie. Ein Fallbericht.

CASE REPORT: After uneventful myopic LASIK, both interfaces of a 31-year-old, healthy male patient showed 5 days (right eye) and 7 days (left eye) postoperatively a diffuse, multifocal infiltration confined to the flap interface which was interpreted as a diffuse lamellar keratitis, stage 2-3. The routine postoperative treatment with local antibiotics and steroids was intensified to local steroids hourly. At that time intraocular pressure (IOP) was 19 mmHg (right) and 18 mmHg (left) (centrally measured by Goldmann applanation tonometry). Following 2 weeks under this therapy the keratitis did not resolve and IOP increased up to 30 mmHg. Local and systemic antiglaucomatosa were administered and IOP was reduced to 22 and 24 mmHg, respectively. Corneal interface infiltration, however, remained unchanged. Only the complete stop of the local corticosteroids induced a rapid regression and corneal transparency returned. IOP was normalized down to 10 mmHg without additional therapy. DISCUSSION: 1) It is essential to measure IOP in the early postoperative phase after LASIK, especially in cases of corneal haze. 2) After corneal refractive surgery with high corneal ablation, IOP data in the upper range has to be interpreted as pathological. 3) Steroid-induced lamellar keratopathy is postulated as being a separate entity. 4) In cases of stromal infiltration after LASIK and increased IOP, local steroids have to be reduced immediately.

[Prognosis of corneal transplantation after penetrating eye injury]. / Prognose von Korneatransplantationen nach Bulbusperforation.

BACKGROUND: The success of penetrating keratoplasty (PKP) after penetrating eye injuries is often worse than in keratoplasty with Fuchs' endothelial dystrophy. However, comparable investigations are rare. Therefore, we have retrospectively analyzed the results and complication rates of PKPs in patients who experienced penetrating eye injuries. PATIENTS AND METHODS: Between 1990 and 1997 forty-four patients who received a corneal transplant at Kiel University Eye Hospital after penetrating eye injury (study group S) were analyzed. 29 patients were re-examined (visual acuity testing, slit lamp microscopy, applanation tonometry, stereo testing, corneal TMS topography, keratometry, endothelial microscopy, perimetry, indirect retinoscopy, testing of the retinal visual acuity and probatory contact lens fitting). Postoperative follow-up ranged between 1 and 6 years (median 3 years). The results were compared to a group of corneal grafts performed in patients with Fuchs' endothelial dystrophy (K, n = 18 patients, 25 eyes, median follow-up 2.8 years). RESULTS: 38males and 6 women had had a bilateral visual acuity of 0.8 or better before the accident, except for three cases. At the time of eye injury the patients' age ranged from 4 to 76 years. The eye trauma was caused by splinters of metal (45 %), glass (20 %), wood (16 %) or stone (11 %). In 73 % of the cases the injury was confined to the anterior segment of the eye (S1). The posterior part of the eye was involved in 27 % (S2). BCVA of S before keratoplasty (KP) was 1/15 on average (K 0.2), at least one year after KP 0.25 (K 0.4); post KP S1 was better than S2 (p = 0.0234), and K better than S (p = 0.0009). In group S 29 patients received a graft at random because of a central corneal scar, 14 patients received an HLA-typed graft with 2.3 mismatches on average. 93 % of the grafts (41 patients) were clear at the last examination, 8 patients showed rejection episodes, half of them were reversible. 5 patients received a second graft because of an irreversible rejection or endothelial decompensation. BCVA improved by at least one line in 84 % in S (K 92 %). BCVA was unchanged after KP in 6.8 % (K 8 %). In 9.1 % of S BCVA after KP was worse (K 0 %). 32 out of 44 patients had a BCVA of 0.1 or better after the last check-up, 13 out of 44 patients presented with a BCVA of 0.5 or better (K40 %). 15 out of 29 patients separately tested showed stereopsis compared to 8 preoperatively in S. In 48 % of the patients studied stereovision could not be restored. 82 % of the patients suffered from topographical irregular astigmatism in S, the superficial geometry of recipient's cornea seems relevant for astigmatism of the graft. Frequent postsurgical complications consisted of secondary glaucoma (S 27 %, K 4 %), immunological rejections (S 18 %, K 0 %), and amblyopia (S 14 %, K 0 %). CONCLUSION: Compared to patients with Fuchs' dystrophy the results of grafting after eye injuries are significantly worse. This relates to BCVA, astigmatism, frequency of secondary glaucoma and graft rejection.

[Implantation of toric intraocular lenses for correction of high post-keratoplasty astigmatism]. / Implantation torischer Intraokularlinsen zur Korrektur hoher postkeratoplastischer Astigmatismen.

BACKGROUND: High postkeratoplasty astigmatism remains a challenge for the surgeon. First experiences after implantation of a toric PMMA IOL in three eyes from patients with cataracts are reported. MATERIALS AND METHODS: After routine phacoemulsification we implanted an individually manufactured toric PMMA posterior chamber IOL via a sclerocorneal 6-mm tunnel incision in three postkeratoplasty eyes with high, topographically relatively regular astigmatism. One eye with the intraoperative aspect of circular zonular instability also received a capsular tension ring. A complete standard ocular examination was performed pre- and postoperatively including corneal topography, evaluation of anterior chamber depth, ultrasonic biomicroscopy and perimetry. RESULTS: Implantation and intraoperative alignment of the toric IOL were uneventful. The refractive astigmatisms of 5.0, 6.0 and 7.5 cyl D preoperatively, were reduced to 2.0, 1.75 and 3.0 cyl D, 10 and 12 months postoperation, respectively. The eye with the capsular tension ring showed no morphological or refractive changes during follow-up. In the other two eyes we observed IOL rotation of 20 and 30, respectively after 6 months. There were no posterior capsule opacification or capsular folds in the optical centre. CONCLUSION: Toric IOL technology allows enhancement of IOL surgery with improved refractive outcome. Simultaneous implantation of a capsular tension ring may improve long-term stability.

T cell cytokines determine the severity of experimental IgA nephropathy by regulating IgA glycosylation.

Hyperfunction of Th2 cells and aberrant glycosylation of IgA have been proposed independently as factors in the pathogenesis of IgA nephropathy (IgAN), the most common form of glomerulonephritis. To investigate the relationship between Th2 cytokines and IgA glycosylation in the genesis of IgAN, we induced IgAN in C3HeB and BALB/c mice by oral immunization and intranasal challenge with Sendai virus. Although both strains of mice developed microhaematuria and glomerular IgA immune deposits to similar degrees, only BALB/c mice developed significant renal insufficiency. More profound reductions of terminal galactosylation and sialylation occurred in Sendai virus-specific IgA from BALB/c versus C3HeB mice, and splenocytes from immunized BALB/c mice produced more Th2 and less Th1 cytokines compared to C3HeB mice when stimulated with antigen in vitro. Furthermore, the decreased glycosylation of IgA elicited by Th2 cytokines in vitro was blunted by the addition of IFN-gamma. We conclude that increased production of Th2 cytokines can lead to abnormalities in IgA glycosylation, which in turn promote heightened phlogistic responses to IgA immune complexes lodging in the glomerulus. We suggest that a relative or absolute increase in Th2 cytokine production in response to mucosal infection is a significant pathogenic factor in human IgAN.

Persisting diplopia after bilateral laser in situ keratomileusis.

We present a case of persisting diplopia after bilateral laser in situ keratomileusis in a patient with high anisometropia and amblyopia. Treatment of this complication by ocular-muscle surgery was not possible because of missing fusion. We suggest that, especially in cases with anisometropia, a complete examination of binocularity be performed before refractive surgery.

Might and magic, lust and language--the eye as a metaphor in literature. Notes on the hierarchy of the senses.

The special anatomy and physiology of the eye predestine it to function as the primary mediator between the world within us and the world without. The way we respond to and reflect on our world is strongly associated with our eyesight. Since antiquity literature, the most important medium for propagating knowledge, has abounded with symbols for the motif 'eye,' symbolizing the responsibility, independence and significance of the visual sense. Today the mechanisms of the modern information media engulf us with new and permanent stimuli. If we surrender ourselves uncritically to this profusion of images, we risk 'overstraining' our sense of sight and losing the connection between perception and cognition. In the following a few references to the international non-medical literature may explain and illustrate the functions of the eye as a metaphor for the mind and describe the past and the prospects of visual perception.

[Photo-therapeutic keratectomy (PTK)--a successful treatment for Thiel-Behnke dystrophy and its recurrence]. / Phototherapeutische Keratektomie (PTK). Eine erfolgreiche Therapiemethode bei Thiel-Behnke-Dystrophie und deren Rezidiven.

UNLABELLED: In recent years good results after treatment of different superficial corneal pathologies with the excimer laser 193 nm have been reported. Thiel-Behnke dystrophy is a hereditary form of anterior stromal dystrophy, a promising layer for successful phototherapeutic keratectomy (PTK). This type of dystrophy was first described in 1967 in Kiel. PATIENTS AND METHODS: Ten members of the original family of 1967 were re-examined at the University Eye Hospital, Kiel. A phototherapeutic keratectomy was performed in six eyes because of the typical honeycomb corneal surface irregularity and superficial haze. Two of these eyes had a recurrence of the primary disease on the graft. Four eyes had been untreated so far. The best spectacle corrected visual acuity preoperatively was between 20/200 and 20/40. For all treatments the MEL 60 excimer laser (Aesculap Meditec) was used. To even out the peaks and valleys of the irregular surfaces, modulating agents were applied in decreasing concentrations. The follow-up period is now between 8 months and 4 years. RESULTS: All eyes showed significant visual improvement postoperatively with a best spectacle corrected visual acuity of 20/32 and higher. In one of the postkeratoplasty eyes with the longest follow-up after PTK, the original disease has begun to recur. CONCLUSIONS: Phototherapeutic keratectomy is a successful therapy for Thiel-Behnke dystrophy; it results in quick recovery of patients and their vision. Stable visual acuity and corneal transparency have been observed that last for years. Recurrences after penetrating keratoplasty or after PTK can be positively retreated. A (re-) keratoplasty may be postponed or avoided.

[Mementos of the Berlin-Jewish ophthalmologist Oskar Fehr (1871-1959)]. / Eine Spurensuche, die in Wien begann: Der Berliner jüdische Augenarzt Oskar Fehr (1871-1959).

Anti-Semitism and National Socialism destroyed the existence of many individuals. Their names and biographies disappeared into oblivion. The bequest of ophthalmo--historical papers by Ms. Jutta Lauber, daughter of the Austrian ophthalmologist Hans Lauber (1876-1952), allowed us to trace the fate of the Jewish ophthalmologist Oskar Fehr (1871-1959). In the first decades of the 20th century Oskar Fehr was an internationally renowned ophthalmic surgeon and pathologist. Disregarding political adversities and ignoring personal losses and hardships he dedicated his life to the service of human health.

Relative or Absolute Standards in Assessing Medical Knowledge Using Progress Tests.

Norm-referenced pass/fail decisions are quite common in achievement testing in health sciences education. The use of relative standards has the advantage of correcting for variations in test-difficulty. However, relative standards also show some serious drawbacks, and the use of an absolute and fixed standard is regularly preferred. The current study investigates the consequences of the use of an absolute instead of a relative standard. The performance of the developed standard setting procedure was investigated by using actual progress test scores obtained at the Maastricht medical school in an episode of eight years. When the absolute instead of the relative standard was used 6% of the decisions changed: 2.6% of the outcomes changed from fail to pass, and 3.4% from pass to fail. The failure rate, which was approximately constant when using the relative standard, varied from 2% to 47% for different tests when an absolute standard was used. It is concluded that an absolute standard is precarious because of the variations in difficulty of tests.

Refractive changes after phototherapeutic keratectomy.

PURPOSE: To evaluate refractive error changes after phototherapeutic keratectomy (PTK). SETTING: University Eye Hospital, Kiel, and University Eye Hospital, Hulle, Germany. METHODS: The MEL 60 excimer laser (Aesculap Meditec) was used in all cases. To even out the peaks and valleys of irregular surfaces, modulating agents were applied. The study included 45 patients with various preoperative corneal diseases: central scars, recurrent erosions, corneal dystrophies, and surface irregularities. Subjective and objective refraction, keratometry, slitlamp photography, and corneal topography were performed preoperatively and postoperatively. The follow-up was up to 24 months. RESULTS: Twenty-six patients had stable postoperative refractions. Thirteen patients developed a hyperopic shift; the highest observed amount was +4.0 diopters. In seven patients, the astigmatic error increased, although no significant change in axis was measured. Three patients had a myopic shift. CONCLUSION: After PTK, all types of refractive change can occur. The greatest risk is that of a hyperopic shift. We saw a correlation between the degree of hyperopia and the ablation depth. Methods for preventing such changes include (1) a large treatment zone, (2) use of a polishing program involving a low viscosity fluid at the end of the laser procedure, (3) a two-step treatment in selected cases to avoid ablations that are too deep.

["Coca-Koller" and hist friends. On the 140th birthday of the Vienna Jewish trio: Carl Koller (1857-1944), Sigmund Lustgarten (1857-1911) and Sigmund Freud (1856-1939)]. / "Coca-Koller" und seine Freunde. Zum 140. Geburtstag des jüdisch-wienerischen Trios: Carl Koller (1857-1944), Sigmund Lustgarten (1857-1911) und Sigmund Freud (1856-1939).

The lives of Carl Koller (1857-1944), Sigmund Lustgarten (1857-1911) and Sigmund Freud (1856-1939) are characterized by several interesting similarities. In their early achievements in medical research they were pathfinders of the first successful local anesthetic: cocaine. All three became later victims of antisemitism. Attention is paid to their personal relationship during their time in Vienna, on occasion of the 140th anniversary of their birth.

[Macular combined malformation (hamartoma) of the retina and retinal pigment epithelium]. / Makuläre kombinierte Malformation ("Hamartom") der Netzhaut und des retinalen Pigmentepithels.

BACKGROUND: Combined malformations (hamartomas) of the retina and the retinal pigment epithelium are extremely rare. Confusion of these pigmented lesions with choroidal melanomas or other malignancies is possible. MATERIALS AND METHODS: We present the cases of a 7-year-old girl who developed accommodative convergent strabism and the case of an 8-year-old boy with deterioration of visual acuity in the left eye. On examination the anterior segments were normal in both cases. Funduscopically both eyes showed a centrally located large, partly pigmented and slightly prominent tumor, which extended fanlike into the normal-appearing retina. Both lesions were partly obscured by grayish-white, semitranslucent and thickened retina with retinal folds and overlying tortuous vessels. On follow-up examination one lesion seemed to be slightly more pigmented whereas the other lesion remained unchanged. RESULTS AND DISCUSSION: Combined malformations of the retina and the retinal pigment epithelium were originally described as clinical entities (hamartomas) by Gass in 1973. A few additional cases were subsequently published by McLean in 1976, by Laqua and Wessing in 1979 and some other authors. Laqua and Wessing were the first to give a report of a histologic study in one case with a macular lesion that showed two distinguishable components. The outer pigmented portion consisted of hypertrophied retinal pigment epithelium; the inner unpigmented portion consisted of a malformed and thickened retina which, however, showed normal layering. The clinical characteristics are usually diagnostic. Fluorescein angiography is helpful in establishing the diagnosis and ruling out differential diagnoses. CONCLUSION: Although long-term follow-up did not show evidence of growth patients with combined malformation of the retina and retinal pigment epithelium should be followed up regularly.

Histopathological comparison of photorefractive keratectomy and laser in situ keratomileusis in rabbits.

BACKGROUND: After 193 nm excimer laser photorefractive keratectomy (PRK) for myopia, superficial opacities in the ablation zone and regression of refractive results can occur. Clinical studies have emphasized that corneal clarity and early refractive stability can be achieved with laser in situ keratomileusis (LASIK). We present clinical and histological results that compare PRK and LASIK for the treatment of myopia in rabbits. MATERIALS AND METHODS: We treated 12 New Zealand white rabbits with PRK and 12 with LASIK using a 193-nm excimer laser (Aesculap Meditec). In both techniques, the identical excimer software and ablation parameters of -10 D treatment depth were used. Six months after surgery, all eyes were removed and prepared for light, fluoresence and transmission electron microscopy. RESULTS: At the time of enucleation, nine eyes in the PRK group had a moderate to high degree of haze (grade 2 to 3), whereas after LASIK, all corneas showed an almost clear interface in the ablation zone. Correspondingly, all histological investigations after LASIK showed a regular stromal architecture, in contrast to the obvious anteri or stromal disorganization after PRK. CONCLUSION: The preserved integrity of the superficial corneal layers after LASIK ensures quick wound healing with minimal tissue proliferation, resulting in a transparent corneal interface. This technique appears especially suitable for correcting high myopia.