Cystoid macular edema in a patient with acquired immunodeficiency syndrome and past ocular history of cytomegalovirus retinitis after initiation of protease inhibitors

Purpose: To describe a patient with acquired immunodeficiency syndrome (AIDS) who presented with cystoid macular edema (CME) which was not associated with active cytomegalovirus (CMV) retinitis or AIDS-related microvasculopathy. Method: A 32-year-old man with AIDS and a past ocular history of inactive CMV retinitis was placed on protease inhibitors when his CD4⁺ T lymphocyte counts dropped to 8 cells/mm³. Three months later, after his CD4⁺ T lymphocyte counts had increased to 196 cells/mm³ he complained of micropsia and metamorphopsia in his right eye of 1 week duration. The patient had a complete ocular examination including fluorescein angiography (FA). Results: Visual acuity (VA) was 7/10 OD. Fundus examination revealed CME and inactive CMV retinitis, and FA demonstrated CME and a hot disc. Two transseptal injections of corticosteroids were administered 2 weeks apart in the right eye as treatment of the CME. The patient reported gradual visual improvement and 6 weeks later, his VA was 10/10^-2. CME had resolved clinically and angiographically. Conclusions: CME in our case is associated with inactive CMV retinitis and gradually increasing number of CD4⁺ T lymphocytes after initiation of treatment with protease inhibitors. It may be amenable to regional administration of corticosteroids without reactivation of retinitis. This revised version was published online in July 2006 with corrections to the Cover Date.     

An insertion/deletion polymorphism in the gene encoding angiotensin converting enzyme is not associated with generalised vitiligo in an English population

Vitiligo is an acquired hypomelanotic skin disorder characterised by circumscribed depigmented macules resulting from the loss of functional melanocytes from the cutaneous epidermis and autoimmunity has been suggested to play a role in the pathogenesis of the disease. Recently, an insertion/deletion (I/D) polymorphism of a 287-base pair repetitive sequence in intron 16 of the angiotensin converting enzyme (ACE) gene has been associated with autoimmune disease and with the development of vitiligo. In this study, the distribution of ACE gene I/D genotypes was investigated in a population of 106 English patients with generalised (non-segmental) vitiligo and 174 ethnically matched healthy controls using a restriction fragment length polymorphism-polymerase chain reaction genotyping method. No significant difference in the frequencies of II, ID and DD genotypes was detected between vitiligo patients and control subjects (P=0.35). The same result was evident for the genotype distribution in vitiligo patients with an autoimmune disease and for those without when compared with controls (P=0.33 and P=0.53, respectively). In addition, the results indicated that the D allele was not significantly over-represented in the group of patients with vitiligo compared with controls (P=0.42) and that this was also the case for patients with and without associated autoimmunity (P=0.40 and P=0.62, respectively).     

Course of macular edema in uveitis under medical treatment

OBJECTIVE: To describe the response of uveitic macular edema to various treatment methods using optical coherence tomography (OCT). METHODS: This is a prospective study of consecutive uveitis patients with macular edema in at least one eye. The patients received medical treatment. Best corrected Snellen Visual Acuity (BCVA) and tomographic features of the macula, including macular thickness measurement, were obtained at one, three, six, and 12 months after commencing treatment. RESULTS: Eighty-one eyes of 58 patients were analyzed. Complete resolution of macular edema occurred in 38 eyes (47%). The average BCVA was 20/34 logarithm of minimum angle of resolution (-logMAR, 0.2 +/- 0.3) upon study entry and 20/27 (-logMAR, 0.13 +/- 0.29) upon study completion. The difference was statistically significant (p = 0.04). The corresponding mean retinal thickness at the central fovea was 319 +/- 150 microm at the beginning of the study compared to 241 +/- 125 microm at 12 months (p < 0.001). A weak but statistically significant correlation between the reduction of macular thickness and the improvement of BCVA (r = 0.3, p = 0.01) was found. Thirteen of the 43 eyes (30%) with persistent macular edema had a more than 15% reduction of macular thickness compared to baseline, whereas 10 eyes (23, 3%) had a more than 15% increase in macular thickness. Statistical analysis indicated that the presence of an epiretinal membrane and an OCT pattern of diffuse macular edema was a significant factor associated with medical treatment failure. CONCLUSION: This study demonstrates the overall favorable visual prognosis of uveitic macular edema under medical treatment. The presence of an epiretinal membrane is an important factor associated with medical treatment failure.     

Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease).

OBJECTIVES: We tested the hypothesis that defective interactions between adhesion junctions and the cytoskeleton caused by the plakoglobin mutation in Naxos disease lead to remodeling of gap junctions and altered expression of the major gap junction protein, connexin43. BACKGROUND: Naxos disease, a recessive form of arrhythmogenic right ventricular cardiomyopathy, is associated with a high incidence of arrhythmias and sudden cardiac death. Naxos disease is caused by a mutation in plakoglobin, a protein that links cell-cell adhesion molecules to the cytoskeleton. METHODS: Myocardial expression of connexin43 and other intercellular junction proteins was characterized in 4 patients with Naxos disease. Immunohistochemistry was performed in all 4 patients, and immunoblotting and electron microscopy were performed in 1 patient who died in childhood before overt arrhythmogenic right ventricular cardiomyopathy had developed. RESULTS: Connexin43 expression at intercellular junctions was reduced significantly in both right and left ventricles in all patients with Naxos disease. Electron microscopy revealed smaller and fewer gap junctions interconnecting ventricular myocytes. Mutant plakoglobin was expressed but failed to localize normally at intercellular junctions. Localization of N-cadherin, alpha- and beta-catenins, plakophilin-2, desmoplakin-1, and desmocollin-2 at intercalated disks appeared normal. CONCLUSIONS: Remodeling of gap junctions occurs early in Naxos disease, presumably because of abnormal linkage between mechanical junctions and the cytoskeleton. Gap junction remodeling may produce a coupling defect which, combined with the subsequent development of pathologic changes in myocardium, could contribute to a highly arrhythmogenic substrate and enhance the risk of sudden death in Naxos disease.     

Isolated pituitary granuloma by atypical Mycobacterium in a nonimmunosuppressed woman

A 32-year-old woman presented with a 10-day history of fever (38.0 degrees C), headaches, nausea, vomiting and a 6-month history of diabetes insipidus and amenorrhoea. Two months previously she had undergone a surgical drilling of the right mastoid area because of mastoiditis. Endocrine investigation showed elevated serum prolactin levels, secondary adrenal and gonadal failure and a normal thyroid function. Cranial MRI scan revealed a contrast enhancing intrasellar mass (approximately 2 cm) of heterogeneous appearance with suprasellar extension and thickening of the pituitary stalk. Lumbar puncture was suggestive of aseptic meningitis. The Ziehl-Neelsen stain of cerebrospinal fluid (CSF) and the tuberculin skin test were both negative. The pituitary mass was removed with a transsphenoidal approach. Histological examination demonstrated destruction of the adenohypophysis by epithelioid granulomas with partial caseous necrosis and microabscess formation, suggestive of a mycobacterial infection. A polymerase chain reaction analysis performed on paraffin-embedded tissue was positive for mycobacterial DNA. According to the individual 16S sequence, it was identified as Mycobacterium malmoense, an atypical nontuberculous mycobacterium (NTM). In conclusion, this is the first case of an isolated pituitary granuloma caused by an NTM infection in a nonimmunosuppressed patient.     

Neurochemical underpinning of hemodynamic response to neuropsychiatric drugs: A meta- and cluster analysis of preclinical studies

Functional magnetic resonance imaging (fMRI) is an extensively used method for the investigation of normal and pathological brain function. In particular, fMRI has been used to characterize spatiotemporal hemodynamic response to pharmacological challenges as a non-invasive readout of neuronal activity. However, the mechanisms underlying regional signal changes are yet unclear. In this study, we use a meta-analytic approach to converge data from microdialysis experiments with relative cerebral blood volume (rCBV) changes following acute administration of neuropsychiatric drugs in adult male rats. At whole-brain level, the functional response patterns show very weak correlation with neurochemical alterations, while for numerous brain areas a strong positive correlation with noradrenaline release exists. At a local scale of individual brain regions, the rCBV response to neurotransmitters is anatomically heterogeneous and, importantly, based on a complex interplay of different neurotransmitters that often exert opposing effects, thus providing a mechanism for regulating and fine tuning hemodynamic responses in specific regions.