Treatment escalation in patients not responding to pharmacotherapy, psychotherapy, and electro-convulsive therapy: experiences from a novel regimen using intravenous S-ketamine as add-on therapy in treatment-resistant depression.

A lack of response despite maximum therapy is common in patients fulfilling criteria of treatment-resistant depression. Therefore, innovative strategies for treatment escalation are warranted. Here, we report the clinical experiences associated with a novel therapeutic regimen combining electroconvulsive therapy and repeated intravenous S-ketamine treatment in three patients. The combined therapy was feasible and had no serious side effects. All patients responded to the new treatment option. The augmentative effect of sub-anesthetic S-ketamine on ECT is discussed.

Structural changes of the trabecular meshwork in different kinds of glaucoma.

The morphology of the trabecular meshwork in three types of open angle glaucoma: primary open angle glaucoma (POAG), corticosteroid-induced glaucoma and pigmentary glaucoma (PG) are described. Ageing is one major risk factor for development of POAG. It is assumed that preexisting age-related changes of the trabecular meshwork (TM) play a role for the development of increased outflow resistance and intraocular pressure (IOP) in various types of glaucoma. These age-related changes in the TM develop concomitant with that of presbyopia. Therefore the functional relationship between ciliary muscle (CM) and TM and the age-related changes in morphology of the outflow system are described first. One main finding in the ageing TM concerns changes of the elastic fiber network and the anterior elastic tendons of the CM. There is an increase in thickness of the sheath of the elastic fibers. Cross-sections through these fibers with their sheath appear as extracellular plaques and were therefore termed "sheath derived plaques" (SD-plaques). Morphologically, the TM changes in POAG resemble that of the ageing TM, but in POAG there is a significant increase in SD-plaques compared to age-matched controls. This increase is due to fine fibrils and other components of the extracellular matrix (ECM) that adhere to the sheaths of the elastic fibers and their connections to the inner wall endothelium. In POAG eyes there is also a marked loss of TM cells, at places leading to fusion and thickening of trabecular lamellae. In steroid-induced glaucoma there is also an increase in fine fibrillar material in the subendothelial region of SC. In contrast to POAG eyes these fibrils do not adhere to the sheath of the elastic fibers but are deposited underneath the inner wall endothelium. The main finding in steroid-induced glaucoma is an accumulation of basement membrane-like material staining for type IV collagen. These accumulations are found throughout all layers of the TM. In pigmentary glaucoma loss of cells was more prominent than in POAG eyes. Presumably, this cell loss occurs after overload of TM cells with pigment granules. Denuded TM lamellae fuse and the TM collapses. In the subendothelial region of these collapsed TM areas an increase in ECM presumably due to underperfusion was observed. At other places SC was occluded and the cribriform region appeared disorganized. In most parts of the circumference of the eye, the TM cells contained pigment granules. Occlusion of TM spaces by pigment granules or cells loaden with pigment was not seen in eyes with PG.

Digit ratio (2D:4D) and academic success as measured by achievement in the academic degree "Habilitation".

INTRODUCTION: Prenatal androgen exposure has important organizing effects on brain development and therefore on future behavior. Previous research has shown, that the ratio between index finger (2D) and ring finger (4D) (2D:4D) could function as a marker of prenatal androgen effects, with a relatively shorter 2D indicating a higher prenatal androgen exposure. 2D:4D is associated with status-seeking and competitive behavior but also with altruism. Therefore, 2D:4D should be related to academic success. METHODS: We examined the 2D:4D of both hands, as well as the difference between both variables (Dr-l), of 209 university graduates (74 women) employed at the Medical Faculty of the Friedrich-Alexander-University Erlangen-Nürnberg, Germany, and we assessed the relationship of these variables with academic career performance. Career performance was measured by the number of publications as first or last author, and by achievement of an academic degree used in many European countries, the so-called "Habilitation". RESULTS: In a within-sex analysis we found a non-monotonic association between the right hand digit ratio and the probability of having a "Habilitation" in females. Academic success, measured by the number of publications as first or last author and the probability of a "Habilitation", increases with age. In agreement with the literature, we found higher academic success in men. CONCLUSION: We found a non-monotonic relationship between right hand 2D:4D and academic success in females. However, the significance of this relationship was weak.

Ultrastructural changes associated with dexamethasone-induced ocular hypertension in mice.

PURPOSE: To determine whether dexamethasone (DEX)-induced ocular hypertension (OHT) in mice mimics the hallmarks of steroid-induced glaucoma (SIG) in humans, including reduced conventional outflow facility (C), increased extracellular matrix (ECM), and myofibroblasts within the outflow pathway. METHODS: Osmotic mini-pumps were implanted subcutaneously into C57BL/6J mice for systemic delivery of DEX (3-4 mg/kg/d, n = 31 mice) or vehicle (n = 28). IOP was measured weekly by rebound tonometry. After 3 to 4 weeks, mice were euthanized and eyes enucleated for ex vivo perfusion to measure C, for electron microscopy to examine the trabecular meshwork (TM) and Schlemm's canal (SC), or for immunohistochemistry to examine type IV collagen and α-smooth muscle actin. The length of basement membrane material (BMM) was measured along the anterior-posterior extent of SC by electron microscopy. Ultrastructural changes in BMM of DEX-treated mice were compared against archived human SIG specimens. RESULTS: Dexamethasone increased IOP by 2.6 ± 1.6 mm Hg (mean ± SD) over 3 to 4 weeks and decreased C by 52% ± 17% versus controls. Intraocular pressure elevation correlated with decreased C. Dexamethasone treatment led to increased fibrillar material in the TM, plaque-like sheath material surrounding elastic fibers, and myofibroblasts along SC outer wall. The length of BMM underlying SC was significantly increased in mice with DEX and in humans with SIG, and in mice decreased C correlated with increased BMM. CONCLUSIONS: Dexamethasone-induced OHT in mice mimics hallmarks of human SIG within 4 weeks of DEX treatment. The correlation between reduced C and newly formed ECM motivates further study using DEX-treated mice to investigate the pathogenesis of conventional outflow obstruction in glaucoma.

Characterization of the mucocutaneous junction of the human eyelid margin and meibomian glands with different biomarkers.

PURPOSE: To investigate the morphology of the human eyelid margin and the presence of different cytokeratins, mucins and stem cell markers within the skin epithelium, mucocutaneous junction (MCJ) and palpebral conjunctiva. METHODS: Eyelids of body donors were investigated histologically and ultrastructurally as well as by immunohistochemical methods using antibodies to cytokeratins 1, 4, 7, 8, 10, 13, 14, 15, and 19; mucins MUC1, MUC4, and MUC5AC and potential stem cell markers K15, BCRP/ABCG2, integrin ß1, and N-cadherin. RESULTS: The expression pattern of cytokeratins, mucins and stem cell markers varied across the different epithelia of the human eyelid. Within the MCJ, CK7, 15 and 19 were absent, whereas the epithelium reacted positive to antibodies to CK1, 4, 8, 10, 13 and 14. Reactivity was also observed for MUC1 and MUC4, but not for MUC5AC. No reactivity was determined for K15, BCRP/ABCG2 and integrin ß1 in the area of the MCJ epithelium but a strong reactivity was present for N-cadherin. CONCLUSIONS: The present immunohistochemical findings lead to a better characterization of the MCJ. Additionally, the knowledge of distribution of biomarkers like cytokeratins, mucins and stem cells can be useful in the investigation of MCJ disturbances which occur in several disorders of the meibomian glands and the lid epithelium in the course of dry eye syndrome and especially meibomian gland dysfunction.

Morphologic changes in the outflow pathways of bovine eyes treated with corticosteroids.

PURPOSE: To analyze morphologic changes in the trabecular meshwork (TM) of bovine eyes treated with topical prednisolone and exhibiting elevated intraocular pressure for 4 weeks. METHODS: The TM of four adult Braford cow eyes treated with 0.5% prednisolone eye drops three times daily for 7 weeks and their contralateral eyes treated with artificial tear preparation and that of two adult untreated Braford cows and untreated young calves eyes were analyzed with light and electron microscopy. Increased extracellular matrix (ECM) under the outflow loops was evaluated quantitatively. Additionally, deparaffinized tissue of treated eyes was labeled with an antibody against type VI collagen for immunocytochemistry. RESULTS: In steroid-treated eyes ECM (plaques) accumulated under the endothelium of the inner wall of the outflow loops. On electron microscopy, this material contained fine fibrils that labeled for type VI collagen. Plaques were also seen in the contralateral controls of the treated animals but here they were significantly less in amount. In the untreated Braford controls and in untreated calf eyes, plaques were nearly absent. In the TM cells of the treated eyes there was a loss of glycogen from the cytoplasm and an increase in basement membrane-like material. These changes were not seen in contralateral eyes or eyes of untreated animals. CONCLUSIONS: Accumulations of ECM in the treated eyes resembled morphologic changes in human eyes with primary open-angle glaucoma and steroid-induced glaucoma. This animal model, therefore, provides a good tool in which to further study the pathogenesis of TM changes in glaucoma.