Complete remission of central nervous system manifestations of IgG4-related disease with rituximab - a case report.

IgG4-related disease (IgG4-RD) is an emerging immune-mediated chronic fibrotic disease characterized by tumour-like mass formation. Reports of brain parenchymal involvement in IgG4-RD are rare and complete treatment-related remission of lesions has never been reported. Here, we present a woman in her mid-50s who developed headache and seizures. Brain magnetic resonance imaging revealed frontal bilateral pachymeningitis and a left frontal lobe parenchymal lesion, and pathologic findings were consistent with an IgG4-RD central nervous system manifestation. She had a history of tumour-like growth around the right optic nerve, orbital and maxillary cavities treated successfully with corticosteroids 28 years ago, and was receiving infliximab as a maintenance therapy for uveitis for the last 14 years. After initial high-dose corticosteroid treatment, the patient was treated with rituximab, and after 3 months, the patient presented with complete remission of IgG4-RD lesions and associated symptoms. This case illustrates the chronic, decades-spanning nature of IgG4-RD, and a complete response to rituximab even with intracerebral mass lesions that had emerged despite the use of infliximab, a therapy previously reported successful in IgG4-RD.

HIV-1 transmission networks in high risk fishing communities on the shores of Lake Victoria in Uganda: A phylogenetic and epidemiological approach.

BACKGROUND: Fishing communities around Lake Victoria in sub-Saharan Africa have been characterised as a population at high risk of HIV-infection. METHODS: Using data from a cohort of HIV-positive individuals aged 13-49 years, enrolled from 5 fishing communities on Lake Victoria between 2009-2011, we sought to identify factors contributing to the epidemic and to understand the underlying structure of HIV transmission networks. Clinical and socio-demographic data were combined with HIV-1 phylogenetic analyses. HIV-1 gag-p24 and env-gp-41 sub-genomic fragments were amplified and sequenced from 283 HIV-1-infected participants. Phylogenetic clusters with ≥2 highly related sequences were defined as transmission clusters. Logistic regression models were used to determine factors associated with clustering. RESULTS: Altogether, 24% (n = 67/283) of HIV positive individuals with sequences fell within 34 phylogenetically distinct clusters in at least one gene region (either gag or env). Of these, 83% occurred either within households or within community; 8/34 (24%) occurred within household partnerships, and 20/34 (59%) within community. 7/12 couples (58%) within households clustered together. Individuals in clusters with potential recent transmission (11/34) were more likely to be younger 71% (15/21) versus 46% (21/46) in un-clustered individuals and had recently become resident in the community 67% (14/21) vs 48% (22/46). Four of 11 (36%) potential transmission clusters included incident-incident transmissions. Independently, clustering was less likely in HIV subtype D (adjusted Odds Ratio, aOR = 0.51 [95% CI 0.26-1.00]) than A and more likely in those living with an HIV-infected individual in the household (aOR = 6.30 [95% CI 3.40-11.68]). CONCLUSIONS: A large proportion of HIV sexual transmissions occur within house-holds and within communities even in this key mobile population. The findings suggest localized HIV transmissions and hence a potential benefit for the test and treat approach even at a community level, coupled with intensified HIV counselling to identify early infections.

Interaction of purified tear lipocalin with lipid membranes.

PURPOSE: The principal lipid-interacting protein in human tears has been reported to be tear lipocalin (Tlc). Tlc has been suggested to scavenge harmful lipophilic substances from the corneal epithelium and to maintain the integrity of the anterior tear film lipid layer by binding and releasing lipid(s) that are accommodated within the protein. Although lipids can be extracted from Tlc, it is still unclear whether Tlc can actually bind to lipid membranes and accept membrane lipids and whether it possesses lipid transfer activity. The purpose of this study was to explore the interaction of Tlc with neutral, anionic, and cationic lipid membranes and to assess the potential of Tlc to facilitate the transfer of either polar or neutral lipids in a lipid transfer assay. METHODS: The binding of Tlc to lipid membranes was assessed by a monolayer technique and fluorescence spectroscopy. The polar lipid transfer activity of Tlc was assessed with a radiometric assay based on the transfer of (14)C-phosphatidylcholine (PC) from PC-liposomes to HDL(3). The neutral lipid transfer activity of Tlc was assayed by measuring the transfer of radioactive cholesteryl ester from LDL to HDL(3). RESULTS: Purified Tlc showed significant surface activity as evidenced by an increase in surface pressure at the air-buffer interface. Likewise, it interacted actively with neutral, anionic, and cationic lipid monolayers, as evidenced by an equal increase in surface pressure despite the surface charge. Enhanced quenching of the single tryptophan residue of Tlc by pyrene and I(-) anion suggested that different protein domains are involved in the interaction of Tlc with oppositely charged lipid membranes. Finally, radiometric assays revealed that Tlc does not possess any neutral or polar lipid transfer activity between lipid vesicles or/and lipoproteins. CONCLUSIONS: Tlc interacted with lipid membranes composed of neutral, cationic, or anionic membranes, which supports a role for Tlc in the maintenance of the tear film interfaces. Tlc did not show any neutral or polar lipid transfer activity whatsoever. The findings suggest that the notion of the role of Tlc as the major lipid-transferring protein in human tears should be revised.

Borderline intellectual functioning: a systematic literature review.

The literature related to people with borderline intellectual functioning (BIF) was systematically reviewed in order to summarize the present knowledge. Database searches yielded 1,726 citations, and 49 studies were included in the review. People with BIF face a variety of hardships in life, including neurocognitive, social, and mental health problems. When adults with BIF were compared with the general population, they held lower-skilled jobs and earned less money. Although some risk factors (e.g., low birth weight) and preventive factors (e.g., education) were reported, they were not specific to BIF. The review finds that, despite the obvious everyday problems, BIF is almost invisible in the field of research. More research, societal discussion, and flexible support systems are needed.

Interaction of fusidic acid with lipid membranes: Implications to the mechanism of antibiotic activity.

We have studied the effects of cholesterol and steroid-based antibiotic fusidic acid (FA) on the behavior of lipid bilayers using a variety of experimental techniques together with atomic-scale molecular dynamics simulations. Capillary electrophoretic measurements showed that FA was incorporated into fluid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine membranes. Differential scanning calorimetry in turn showed that FA only slightly altered the thermodynamic properties of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) bilayers, whereas cholesterol abolished all endotherms when the mole fraction of cholesterol (X(chol)) was >0.20. Fluorescence spectroscopy was then used to further characterize the influence of these two steroids on DPPC large unilamellar vesicles. In the case of FA, our result strongly suggested that FA was organized into lateral microdomains with increased water penetration into the membrane. For cholesterol/DPPC mixtures, fluorescence spectroscopy results were compatible with the formation of the liquid-ordered phase. A comparison of FA and cholesterol-induced effects on DPPC bilayers through atomistic molecular dynamics simulations showed that both FA and cholesterol tend to order neighboring lipid chains. However, the ordering effect of FA was slightly weaker than that of cholesterol, and especially for deprotonated FA the difference was significant. Summarizing, our results show that FA is readily incorporated into the lipid bilayer where it is likely to be enriched into lateral microdomains. These domains could facilitate the association of elongation factor-G into lipid rafts in living bacteria, enhancing markedly the antibiotic efficacy of FA.

Leukocyte rolling and extravasation in surgical inflammation after mechanical and laser-induced trauma in human patients.

Acute inflammations main characteristics are exudation of fluid and plasma proteins and emigration of leukocytes, predominantly neutrophils into inflamed tissue. We have previously demonstrated that leukocyte extravasation can be directly monitored in human patients in vivo after tunnel cataract operation, but at the same time we noticed that only certain manipulations trigger also leukocyte extravasation. To define the type of surgical manipulations triggering leukocyte extravasation, we tested a set of surgical manipulations affecting distinct anatomical components of the conjunctiva. This set included various combinations of epithelial, nerve, and/or blood vessel damage. Manipulations tested here were surgical conjunctival biopsy, low-energy Argon laser treatment (80 mJ) closing a venule temporarily, high-energy argon laser treatment (480 mJ) to occlude a venule firmly, and 193 nm eximer laser-based conjunctival phototherapeutic keratectomy (160 mJ). These manipulations were compared to previous findings on conjunctival inflammation following the standard cataract operation. In mechanical trauma models (cataract operation and conjunctival biopsy) clinical signs of inflammation, number of leukocytes rolling, and number of tissue emigrated leukocytes were notably higher compared to pre-operative levels on one day after the operation. No specific anatomical triggering component for inflammation, including epithelial, nerve, and/or blood vessel damage, was indentified, but rather the trauma mechanism itself appeared to be an essential factor. Surprisingly, in laser-induced traumas no increase in number of rolling cells, rolling velocity slowing, or elevation of tissue emigrated leukocytes took place compared to pre-operative levels. These findings suggest that laser-induced traumas differ fundamentally from the mechanical traumas at all levels of leukocyte extravasation cascade, and at least in our setup, inflammatory reaction can be avoided or triggered depending on surgical method used.

Unilateral photorefractive keratectomy for myopic anisometropia improves contrast sensitivity.

OBJECTIVE: To evaluate visual performance after unilateral photorefractive keratectomy (PRK) performed for >/=2.75-diopter (D) myopic anisometropia. DESIGN: Prospective observational case series. PARTICIPANTS: Eleven patients exhibiting >/=2.75-D myopic anisometropia appropriate for PRK. METHODS: Photorefractive keratectomy was performed on 11 eyes of 11 patients for myopic anisometropia ranging from -2.75 to -9.00 D. Best spectacle-corrected visual acuity (VA), contrast sensitivity (CS), and pattern visual evoked potentials (pVEPs) were measured preoperatively and at 3 and 6 months. MAIN OUTCOME MEASURES: Best spectacle-corrected VA; pVEPs; and CS, measured as the area under the CS curve. RESULTS: Best spectacle-corrected VA increased nonsignificantly 6 months after PRK. A tendency towards decreased latency time of pVEPs for both eyes was observed after PRK. A significant increase in CS occurred after PRK in the operated eye at 6 months, but a tendency toward decreased CS appeared in the unoperated eye at 3 months. Preoperative CS levels, however, were reached at 6 months. CONCLUSIONS: The adult central visual system is sensitive to visual deprivation caused by anisometropia. Imbalance between eyes may improve visual performance in the more emmetropic eye. Anisometropia appears to reduce visual performance in the more myopic eye, but this can probably be reversed by refractive correction.

Direct in vivo monitoring of acute allergic reactions in human conjunctiva.

Immediate allergic reactions are initiated by allergen-induced, specific IgE-mediated mast cell degranulation and involve leukocyte recruitment into the inflamed site. We compared conjunctival signs, symptoms, and in vivo leukocyte rolling and extravasation into sites of inflammation in five patients allergic to birch pollen and in 10 nonallergic controls who received a challenge to birch allergen or histamine. Both the specific allergen in allergic patients and histamine, both in patients and in healthy controls, induced symptoms and signs of an immediate allergic reaction together with leukocyte rolling within the conjunctival blood vessels. However, only allergen, not histamine, caused leukocyte extravasation into the site of inflammation in the allergic patients. Allergen also increased expression of endothelial P-selectin in conjunctival vessels and slowed the rolling of leukocytes which is required for their extravasation from blood circulation into the target tissue. Finally, i.v. heparin strongly reduced the number of slowly rolling cells during allergen- or histamine-induced reactions and this can probably hinder the leukocyte extravasation after allergen exposure. These findings suggest that slow rolling is required for leukocyte extravasation in acute allergic reactions, and it can be inhibited by heparin in vivo in therapeutically relevant conditions.