Persistent mammalian orthoreovirus, coxsackievirus and adenovirus co-infection in a child with a primary immunodeficiency detected by metagenomic sequencing: a case report.

BACKGROUND: We report a rare case of Mammalian orthoreovirus (MRV) infection in a child with a primary immunodeficiency (PID). Infections with Mammalian orthoreovirus are very rare and probably of zoonotic origin. Only a few cases have been described so far, including one with similar pathogenesis as in our case. CASE PRESENTATION: The patient, age 11, presented with flu-like symptoms and persistent severe diarrhea. Enterovirus has been detected over several months, however, exact typing of a positive cell culture remained inconclusive. Unbiased metagenomic sequencing then detected MRV in stool samples from several time points. The sequencing approach further revealed co-infection with a recombinant Coxsackievirus and Adenovirus. MRV-specific antibodies detected by immunofluorescence proved that the patient seroconverted. CONCLUSION: This case highlights the potential of unbiased metagenomic sequencing in supplementing routine diagnostic methods, especially in situations of chronic infection with multiple viruses as seen here in an immunocompromised host. The origin, transmission routes and implications of MRV infection in humans merit further investigation.

Effect of growth factors on the activation of human Tenon's capsule fibroblasts.

PURPOSE: To investigate stimulatory effects of PDGF-AA, PDGF-AB, PDGF-BB, bFGF, IL-1beta, TGF-beta1 and TGF-beta2 on the proliferation and myofibroblast transformation of cultured human Tenon's capsule fibroblasts and to characterize expression of PDGF- and TGF-beta-receptors in these cells. METHODS: To determine cell proliferation, cell number of 2nd passage cultured human Tenon's capsule fibroblasts was measured before and after addition of growth factors using a computer-based cell counter system. Immunoblotting was used to detect and quantitate alpha-smooth-muscle actin (alpha-SMA) expression. Expression of PDGF- and TGF-beta-receptor mRNA was detected by RT-PCR, expression of the corresponding protein was demonstrated using Western blot. RESULTS: A significant increase in proliferation (p < or = 0.05) was detected after exogenous stimulation with PDGF-AA (10 ng/ml and 100 ng/ml), PDGF-AB (10 ng/ml and 100 ng/ml), PDGF-BB (10 ng/ml and 100 ng/ml), bFGF (100 ng/ml), IL-1beta (1 ng/ml and 10 ng/ml), TGF-beta1 (0.5 ng/ml) and TGF-beta2 (0.5 ng/ml). Both TGF-beta1 and TGF-beta2 stimulated expression of alpha-SMA in a dose dependent manner with peak activity at a concentration of 50 ng/ml (TGF-beta1) and 500 ng/ml (TGF-beta2). Protein and mRNA of PDGF-receptor type alpha and type beta and TGF-beta-receptors type I, II and III are expressed in cultured human Tenon's capsule fibroblasts. CONCLUSIONS: The present investigation strongly supports the hypothesis that PDGF-isoforms are major stimulators of proliferation of Tenon's capsule fibroblasts after glaucoma filtering surgery while TGF-beta-isoforms are essential for the transformation of Tenon's capsule fibroblasts into myofibroblasts.

[Correlation between glaucomatous hemifield scotomas in white-on-white perimetry and blue-on-yellow perimetry using the oculus twinfield perimeter]. / Korrelation zwischen glaukomatösen Halbfeldskotomen in der Weiss-Weiss-Perimetrie und in der Blau-Gelb-Perimetrie am Oculus-Twinfield-Perimeter.

INTRODUCTION: The "Twinfield Perimeter" can be used for white-on-white and blue-on-yellow perimetry. Since the normative database which is used fort the calculation of the visual field indices for both strategies is based on data from white-on-white perimetric evaluations of normal persons using the "Tübinger Automatikperimeter", the validity of this approach may be questioned. In the study presented here we compared the correlation of white-on-white (W/W) and blue-on-yellow (B/Y) visual fields in glaucoma patients with a hemifield scotoma. PATIENTS AND METHODS: One eye each from 40 normal persons and from 40 glaucoma patients was included in the study. Both W/W-perimetry and B/Y-perimetry was performed using the "Twinfield Perimeter" (Oculus, Modell 56 900, Wetzlar, Germany). From the sensitivity values determined with the 30/2 strategy, we calculated the mean sensitivity (MS), mean deviation (MD) of the total field and of both hemifields (HMS bzw. HMD) separately. Normal values derived from the normal persons of the present study were compared with the normal values used by the Twinfield Perimeter. To determine the strength of the association of B/Y- and W/W-hemifield scotoma, we calculated the linear correlation coefficient (Pearson's R) between the HMD of B/Y und W/W-hemifields. RESULTS: MS of both glaucoma patients and normal persons were determined to be significantly higher for B/Y visual fields (14.17 +/- 4.15 and 20.97 +/- 3.56) when compared with W/W-visual fields (10.70 +/- 3.19 or 15.98 +/- 3.3). When normal values from the Twinfield Perimeter were applied, the MD for normal persons was calculated to be - 4.69 +/- 3.22 compared with 0 +/- 3.6 when the MD was calculated with the normal values from the study. For both normal values we confirm a strong correlation between HMD-values of W/W- and B/Y-visual fields. CONCLUSIONS: Since the mean sensitivity of B/Y visual fields is higher than the mean sensitivity of W/W visual fields, calculations of the MD of B/Y visual fields of glaucoma patients should be based on normative databases which are derived from B/Y visual fields of normal persons.

[Frequency of reoperations after amniotic membrane transplantation]. / Reoperationsrate nach Amnionmembrantransplantation.

BACKGROUND: Retrospective evaluation of the frequency of reoperations after amniotic membrane transplantation for different pathologic entities. MATERIAL AND METHODS: We included 81 cases of amniotic membrane transplantation (AMT), which were operated on at the university eye clinic Tübingen since 1997 and which had been followed up for at least 12 months. Patient diagnoses were subdivided as follows: conjunctival defects after tumour excision (N = 2), bullous keratopathy (N = 5), external fistula after glaucoma filtering surgery (N = 3), recurrent pterygium (N = 5), symblepharon (N = 6), corneal ulcer with descemetocele (N = 3), non-perforated corneal ulcer (N = 51), perforated corneal ulcer (N = 1), other (n = 5). RESULTS: The overall reoperation rate was determined to be 42 % after a follow-up period of one year. Most frequently, a second AMT (N = 16) and a perforating keratoplasty (N = 16) were performed after the initial AMT. The following reoperation rates were determined for the subgroups: Conjunctival defects after tumour excision (0 %), Bullous keratopathy (60 %), External fistula after glaucoma filtering surgery (67 %), Recurrent pterygium (60 %), Symblepharon (67 %), Corneal ulcer with descemetocele (67 %), Non-perforated corneal ulcer (49 %), Perforated corneal ulcer (100 %). CONCLUSIONS: Particularly in patients with conjunctival defects after tumour excision and with non-perforated corneal ulcers, stabilisation of the ocular surface homeostasis can be achieved with a single amniotic membrane transplantation for at least one year.