[Corneal staphyloma-anterior chamber agenesia-microphakia syndrome]. / Hornhautstaphylom-Vorderkammeragenesie-Mikrophakie-Syndrom (kongenitales anteriores Staphylom).

CASE REPORT: Shortly after birth, a massive enlargement of the right eye was observed in an otherwise healthy male child. The cornea of the affected eye was vascularized and completely cloudy without a sharp border between cornea and sclera. The diagnosis of a congenital glaucoma was made but an operation was not undertaken because of the difficult anatomical situation and the lost function. When the child was almost 3 years old enucleation was performed to prevent complications due to corneal exposure, and to improve the cosmetic aspect. RESULTS: The morphological investigations of the enucleated eye disclosed findings typical of what is called in the literature "congenital anterior staphyloma" or "congenital corneal staphyloma", namely a massively staphylomatous cornea with superficial neovascularization, destruction of Bowman's layer, and absence of Descemet's layer as well as corneal endothelium. Angle structures were completely absent, and the corneal back-side was lined by a pigment epithelial layer and focally by an additional inner layer of non-pigmented epithelium. There was no anterior chamber. The lens was markedly diminished in size (microphakia) and partly embedded in the corneal stroma. Pars muscularis and pars ciliaris of the ciliary body were separated. Elongated, thin ciliary processes were extended towards the small lens while the pars muscularis was fully covered by the retina. CONCLUSIONS: This rare, complex malformation syndrome which can be easily distinguished from primary congenital glaucoma should not be reduced conceptually to the corneal staphyloma because this staphyloma constitutes only a part of the whole. Taking the leading morphological aberrations into consideration we would rather propose the new term " corneal staphyloma- anterior chamber agenesia- microphakia syndrome (CSAMS). We hypothesize that CSAMS may be due to a pathological fusion of the early anterior optic cup. As the posterior eye segment is often normal in CSAMS, a staphyloma excision along with a sclero-keratoplasty might be an alternative therapeutic option to avoid enucleation and restore ambulatory vision.

[Is congenital superior oblique strabismus a paretic disorder?--A magnetic resonance tomographic study]. / Ist der einseitige Strabismus sursoadductorius eine paretische Störung? -- Kernspintomographische Untersuchungen.

BACKGROUND: Recent reports postulate that the concomitant vertical deviation found in congenital superior oblique palsy is due to mechanical abnormalities rather than a congenitally paretic muscle, and is overcome in most patients by fusion. On the basis of the clinical characteristics alone a primary paresis is indeed unlikely. Although intraoperatively a different elasticity of the superior oblique tendon exists in congenital versus acquired cases of superior oblique palsy, preoperatively performed MR imaging shows that the clinical findings in congenital superior oblique muscle malfunction could nevertheless be of paretic origin. MATERIALS AND METHODS: Seventeen consecutive patients (males: n = 13; females: n = 4) were examined. The vertical deviation in adduction was concomitant in vertical versions, the excyclotropia was small and concomitant in all directions of gaze and was less than 10 degrees even after diagnostic occlusion. All patients showed a positive Bielschowsky head tilt phenomenon and large fusional ability. We performed preoperative MR imaging of both orbits in high resolution 3 mm sections in coronal and axial orientations with and without contrast enhancement. RESULTS: In sixteen patients we found a significant reduction in muscle volume or even total aplasia of the superior oblique muscle of the affected side in comparison to the sound muscle on the other side. In contrast, two patients had a full blown clinical picture of a congenital superior oblique palsy but showed symmetrical muscle volumes on both sides in all coronal sections. CONCLUSIONS: Hypoplasia or aplasia of the superior oblique muscle on magnetic resonance imaging provides evidence for a primary paretic cause for the vertical squint found with congenital superior oblique dysfunction. It is not clear, however, whether this is caused by a primary hypoplasia or is of neurogenic origin. Our data together with the consistent difference in tendon morphology of the congenital and acquired forms of superior oblique palsy seem to exclude a purely neurogenic cause for the affection.

MMF and eye disease.

Immunosuppressive treatment has shown to be effective in various ocular inflammatory disorders. Factors limiting their use are the individual response and the rate of side effects. This report summarizes our knowledge about the use of mycophenolate mofetil (MMF) in the treatment of ocular cicatricial pemphigoid (OCP), uveitis, atopic keratoconjunctivitis (AKC), prevention of graft rejection after penetrating keratoplasty (PK) and scleritis. Controlled studies have been performed for prevention of graft rejection after PK, showing MMF as effective in the prevention of graft rejection as cyclosporine A. In experimental uveitis, MMF has been demonstrated to be highly effective in prevention of retinal destruction. A number of studies have now shown that MMF also seems effective in uveitis. There are also studies with smaller patient groups which point out the effectiveness of MMF in OCP, AKC, and scleritis. In most of the studies, the spectrum of side effects was small, compared to other immunosuppressives.

Subcutaneous tumor of the lower eyelid: a potential manifestation of a Dirofilaria repens infection.

PURPOSE: To report a case of Dirofilaria repens presenting as a subcutaneous tumor of the lower eyelid. METHODS: Interventional case report. RESULTS: A 29-year-old man of Greek origin without systemic symptoms presented with a 3-week history of a small painless mass localized in the medial part of the lower eyelid. There was no history of a preceding trauma, injury, or visual impairment; however, the patient had recently been on a holiday in Italy. The lesion persisted after systemic antibiotic treatment. Routine blood tests were normal and the efferent tear ducts were patent. Upon surgical intervention a yellowish, pea-sized cyst-like structure was found beneath the orbicularis muscle and removed in toto. Histologic examination revealed the presence of a wormlike structure with the characteristic features of a single adult Dirofilaria repens nematode. CONCLUSIONS: Infection with the nematode Dirofilaria repens has to be considered in the differential diagnosis of malignant and benign tumors of subcutaneous periocular tissues in patients who traveled to endemic areas.

[Relapsing, therapy refractory episcleritis, paraproteinemia and cutaneous-subcutaneous nodules on arm and hip: manifestations of a necrobiotic xanthogranuloma (NXG)]. / Rezidivierende, therapierefraktäre Episkleritis, Paraproteinämie und kutan-subkutane Knoten an Arm und Hüfte: Manifestationen eines nekrobiotischen Xanthogranuloms (NXG).

BACKGROUND: Necrobiotic xanthogranuloma is a rare granulomatous disease featuring nodular, sometimes ulcerating, skin lesions in association with paraproteinemia and variable organ disease. Eye involvement manifests itself often as periorbital plaque-like infiltrates but also as chronic episcleritis, conjunctivitis, keratitis and scleritis. CASE REPORT: A 49-year-old female patient presented to our hospital with a seven-year history of relapsing bilateral episcleritis refractory to treatment. Her past medical history included an IgG paraproteinemia and C4-deficiency of unknown etiology. A year prior to presentation the patient had undergone biopsy of a skin nodule on her arm which histologically was suspected to be an infectious granuloma. A recurrence of the lesion at the site of biopsy together with a new nodule on the hip prompted us to perform further histological analyses. RESULTS: The histological specimen displayed numerous giant cells of the foreign body and Touton type, some xanthomatous foam cells with cholesterol clefts and collagen necrosis, leading to the diagnosis of NXG. As part of the disease, serology showed an IgG lambda paraproteinemia, elevated cANCA values, a C4 deficiency and a negative rheumatoid factor. No other immunological dysfunction was detected. CONCLUSIONS: NXG is a severe multi-system disorder that may cause various chronic inflammatory conditions of the eye's anterior segment. Its early diagnosis is mandatory as potentially fatal organ complications may arise and the association with lymphoproliferative diseases has been described. Due to the relative rarity of the disease no binding therapeutic regimen exists. Options include alkylating agents in combination with corticosteroids, plasmapheresis and subcutaneous interferon alfa-2 b.

[Intraocular non-Hodgkin's lymphoma and its therapy-- a case series of ten patients]. / Das intraokulare Non-Hodgkin-Lymphom und seine Therapie -- eine Fallserie mit 10 Patienten.

BACKGROUND: The timely and correct diagnosis of intraocular non-Hodgkin's lymphoma represents a huge challenge to clinicians. Two thirds of intraocular lymphomas are a manifestation of a primary CNS lymphoma (PCNSL) arising outside the lymphatic system and are localized in the brain, the meninges or the spinal chord. Ten to twenty percent commence as vitreous or retinal infiltrates mimicking uveitis. Ninety five percent of PCNSL are B cell lymphomas. PATIENTS: Three exemplary cases from a group of ten patients treated between 1998 and 2002 are presented. A table provides a summary of the relevant details of all ten patients. RESULTS: The mean age at presentation was 63.5 years with a female to male ratio of 6 to 4. Nine patients were diagnosed as having intermediate or posterior uveitis, in one patient choroidal metastases were suspected. Six patients had a concomitant CNS lesion while four patients showed isolated intraocular lymphoma only. The presence of a highly malignant B cell lymphoma was proven by vitreous biopsy in nine cases and by stereotactic biopsy of a CNS lesion in one patient. All patients were treated by intravenous chemotherapy, however, no binding recommendations with regard to treatment exist to date. CONCLUSIONS: We give an overview of all current treatment regimens and their pitfalls. At present it is recommended that all patients with proven PCNSL be entered in a multicenter randomized study under the auspices of the Department of Internal Medicine III of the Benjamin-Franklin-University-Hospital, Berlin and the Department of Neurology of the University Hospital of Tuebingen.

[Familial uveitis. Forms and incidence in patients at the University Eye Hospital Tubingen]. / Familiäre Uveitis. Formen und Häufigkeit im Patientengut der Universitäts-Augenklinik Tübingen.

OBJECTIVE: A familial accumulation in some forms of uveitis has rarely been described. The objective of this study was to identify such cases and to examine both clinical course and similarities in the HLA-pattern. METHODS: From 1993 to 2000 all new uveitis patients, who were examined in the uveitis clinic of the University Eye Hospital Tuebingen, were asked about a positive family history. If possible, all affected family members underwent an ophthalmological examination and HLA-typing was performed. RESULTS: In 7 families we found a familial accumulation of uveitis. The underlying etiologies were anterior uveitis in ankylosing spondylitis with HLA-B27 association, anterior uveitis in Blau syndrome with no HLA association, anterior and intermediate uveitis in sarcoidosis with no HLA association, and panuveitis in Behçet's disease with HLA-B51 association. For familial uveitis we calculated an incidence of 0.03 cases per 100,000 persons and year. CONCLUSION: Our data confirm that familial forms of uveitis are very rare. We suggest that these may be subgroups of known uveitis syndromes (e.g. sarcoidosis, ankylosing spondylitis). The factors causing the inheritance are still unknown. By genetic examination of families with uveitis it may be possible to identify single uveitis genes or possible antigens.

Rewiring of CD40 is necessary for delivery of rescue signals to B cells in germinal centres and subsequent entry into the memory pool.

Memory B-cell development is impaired by in vivo blockade of the CD40-CD40 ligand (CD40L) interaction using human Fc immunoglobulin G1 (IgG1)-mouse CD40 fusion protein (CD40-Ig); however, germinal centre (GC) formation is not. We show here that the block in B-cell differentiation in these mice is at the stage of rescue from apoptosis and exit from the GC. Thus, GC from CD40-Ig-treated mice contain a three- to fourfold higher level of apoptotic cells than found in control mice injected with human IgG1 alone. This increase in apoptosis is not caused by a blockade of the CD40L-mediated rescue signal but is the result of an intrinsic defect of GC B cells in CD40-Ig-treated mice to receive rescue signals via CD40. While anti-CD40 stimulation maintained the viability in culture of GC B cells from control mice, it did not rescue GC B cells from CD40-Ig-treated mice. This data is consistent with the notion that a 'rewiring' of the CD40 molecule is induced by CD40 ligation early in the response and is necessary to allow B-cell rescue from apoptosis when they subsequently enter the GC.

Fas-Fas ligand-mediated apoptosis within aqueous during idiopathic acute anterior uveitis.

PURPOSE: Despite ocular immune privilege, (auto)immune-mediated acute anterior uveitis (AAU) is relatively common. However, although relapses of AAU are usually self-limiting, possible regulatory mechanisms remain undefined in humans. Experimentally, Fas-Ligand (FasL)-mediated apoptosis of Fas+ inflammatory cells contributes to the immune privilege within the anterior chamber and provides an explanation for the success of corneal allograft transplantation. Therefore, whether such mechanisms regulate the immune response in AAU was investigated. METHODS: Aqueous and peripheral blood samples from consecutive patients presenting with idiopathic AAU were obtained with consent. Leukocytic phenotype was analyzed by flow cytometry, and apoptosis was determined by both flow cytometry and TdT-dUTP terminal nick-end labeling analysis. Presence of soluble Fas and FasL was determined by western blot analysis and enzyme-linked immunosorbent assay and compared with control aqueous from patients undergoing cataract surgery. The ability of the aqueous to induce apoptosis in a Fas+ Jurkat cell line was also determined. RESULTS: During AAU aqueous-infiltrating Fas+ cells included CD3+ T cells and granulocytes, whereas FasL+ cells comprised predominantly of non-CD3+ T cells. Higher levels of functional soluble FasL were found in aqueous of AAU patients than in normal aqueous, capable of inducing apoptosis in 68.9% +/- 7.6% of Fas+ lymphoid cells. Compared with peripheral blood, the CD4+ T cells infiltrate within aqueous showed significantly increased CD69 and CD25(IL-2r) expression. Flow cytometric analysis of aqueous showed that 9.32% +/- 1.2% of infiltrating non-granulocyte CD45+ cells were apoptotic, confirmed as T cells on subsequent three-color flow cytometric analysis. CONCLUSIONS: Taken together with published experimental data, the present study provides evidence for FasL-mediated apoptotic cell death contributing to the local immune regulation of ocular inflammatory disease and provides a mechanism to account for the self-limiting clinical course of AAU.

[Hyperplasia of sebaceous glands (Fordyce's disease) in an oral mucocutaneous graft: 45-year follow-up]. / Talgdrüsenhyperplasie (Fordyce-Erkrankung) in einem konjunktivalen Mundschleimhauttransplantat: Verlauf über 45 Jahre.

BACKGROUND: Diffuse sebaceous gland hyperplasia in transplanted buccal mucosa is a very rare condition. We report on a further patient with this entity. PATIENT: In 1953, a now 68-year-old man suffered a severe alkali burn. Transplantation of oral mucosa was performed that same day in order to prevent perforation of the eye. Over the following 45 years, the patient developed multiple yellowish nodules within the grafts. Histologically, these nodules proved to be normally differentiated sebaceous glands. CONCLUSIONS: Diffuse sebaceous gland hyperplasia originating from within oral mucosa and developing over an extended period of time is a clinical entity known as Fordyce's disease. It is this a late complication of mucocutaneous transplantation, and although it constitutes mainly a problem of cosmesis, functionally it can lead to aberrant secretion of sebum.

Observations on memory B-cell development.

We dissect in this article the roles of CD40 and its ligand in memory B-cell formation. Our data indicate that CD40 ligation does not directly lead to GC formation but it plays an indirect role related to maturation of helper T cells; signalling is bidirectional, to B cells, via CD40, upregulating cytokine receptor expression and to T cells, via CD40L, causing secretion of cytokines necessary for GC initiation. Later in the GC, CD40 selects mutated B cells for entry into the memory pool. This second T-cell-mediated CD40 ligation has consequences distinct from the first (rescue versus proliferation) that arise from rewiring of CD40 signal transduction pathways.

CD40-mediated regulation of interleukin-4 signaling pathways in B lymphocytes.

The importance of cytokines in controlling immunoglobulin isotype switching is well known. Given the defect in switching to IgG, IgA and IgE isotypes in mice and humans that carry mutations in the CD40 and CD40 ligand genes, we have investigated the role of CD40 ligation in controlling B cell responses to interleukin (IL)-4. We have found that CD40-mediated signals cause a fivefold upregulation of IL-4 receptor (IL-4R) on the B cell surface and that this is associated with a 100-1000-fold increase in the cells' responsiveness to the cytokine. While we found no evidence of increased affinity or structural change of the receptor, we do find that prestimulation of B cells with anti-CD40 antibodies brings about several changes in the IL-4 signaling pathways. Subsequent delivery of IL-4 to CD40-prestimulated cells provokes intracellular signals distinct from those induced in resting B cells in response to IL-4. While resting B cells phosphorylate Jak3 kinase shortly after IL-4 activation, cells pre-incubated with anti-CD40 exhibit active dephosphorylation of this molecule and phosphorylation of proteins of around 45 kDa upon addition of IL-4. The common gamma chain, Jak3 and Jak1 can all be immunoprecipitated in normal amounts with the IL-4R chain after CD40 prestimulation. We show that the observed dephosphorylation of Jak3 may be due to a stable association with the src-homology protein tyrosine phosphatase SH-PTP2. In contrast, the enzyme appears to be inactive and to dissociate very quickly from the signaling complex in cells that are stimulated with IL-4 alone.

CD40 ligation in B cell activation, isotype switching and memory development.

Interaction of CD40 on B cells with its ligand on activated T helper cells is crucial for the generation of mature T-dependent antibody responses. Experimental observations suggest that CD40 ligation acts at several points in B cell differentiation; however, it is not clear whether the consequences of ligation are direct or indirect. While its role in B cell activation is clearly direct we discuss the several ways in which it might drive isotype switching, the influence that it has on the development of memory B cells and the possibility that certain types of T-dependent antibody response are CD40L-independent. Experiments in which the ligation of CD40 is blocked in vivo reveal that early CD40 signals are important for the development of memory B cells but this may only reflect the ability of 'memory precursors' generated by CD40 ligation to accept subsequent programming or survival signals.

Introducing an acute pain service.

An acute pain service in a new district general hospital is described. We have reported incidence of severe pain, common postoperative anaesthetic problems and patient satisfaction in relation to the analgesic technique. Over half the patients were treated by intermittent intramuscular injection of opioid, but increase in the use of continuous intravenous therapy and in particular patient-controlled analgesia, was welcomed by both medical and nursing staff.

[Therapeutic stereotypes among the mentally ill]. / Therapeutische Stereotypien bei psychiatrischen Erkrankungen.

Using mathematical models described by Overall, the authors investigated in a sample of 301 psychiatric inpatients the therapeutic stereotypes in medicating psychotropic drugs and its dependence on symptom, syndrome and diagnostic level. The psychotropic drugs were described in a dimensional representation of psychopathology ('symptomatic space'). Besides dependencey from patient's characteristics as age and clinician's characteristics as special orientation, the therapeutic stereotype is mostly influenced by the symptom level. Only lithium therapy and electroconvulsive therapy are keyed to diagnosis. Getting more familiar with a psychotropic drug increases indications and contraindications on symptom level, the therapeutic stereotype gets more differentiated. The comparison between the therapeutic stereotypes of German and French psychiatrists shows a satisfactory congruence relating to dimensionality and relationships among the drugs.