Intraocular microsporidiosis due to Encephalitozoon cuniculi in a patient with idiopathic CD4+ T-lymphocytopenia

Encephalitozoon cuniculi was documented to cause disseminated microsporidial infection including an iris tumor and endophthalmitis in an adolescent with idiopathic CD4+ T-lymphocytopenia. The diagnosis was established by microscopic, serologic and molecular methods. E. cuniculi (rabbit strain) was identified from the iris tumor, as well as from urine, conjunctival, corneal, and nasal swabs. Treatment with oral albendazole led to rapid improvement. This case raises the possibility of disseminated microsporidial infection in the context of idiopathic CD4+ T-lymphocytopenia and possibly advanced human immunodeficiency virus (HIV) infection, and above all the possibility of intraocular infection with E. cuniculi in humans.

Late postoperative opacification of hydrogel intraocular lenses: analysis of 13 explanted lenses

PURPOSE: We report the clinical, morphological, and ultrastructural findings of 13 consecutively explanted opacified Hydroview(R) (hydrogel) intraocular lenses (IOLs). Our purpose was to provide a comprehensive account on the possible factors involved in late postoperative opacification of these IOLs. PATIENTS AND METHODS: Thirteen consecutive opacified hydrogel IOLs (Hydroview H 60 M, Bausch ; Lomb) were explanted due to the significant visual impairment they caused. The IOLs underwent macroscopical examination, transmission electron microscopy (TEM), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and electrophoresis for protein detection. Three unused control Hydroview IOLs served for comparison. RESULTS: Macroscopical examination showed a diffuse or localized grey-whitish opacification within the IOL optic. TEM confirmed the presence of lesions inside the optic in all the explanted IOLs and revealed 3 patterns of deep deposits: a) diffuse, thick, granular, electron-dense ones; b) small, thin, lattice-like ones, with prominent electron-lucent areas; and c) elongated electron-dense formations surrounded by electron-lucent halos. SEM showed surface deposits on four IOLs. EDS revealed oxygen and carbon in all IOLs and documented calcium, phosphorus, silicon and/or iron in the deposits. Two of the patients with iron in their IOLs had eye surgery prior to their phacoemulsification. Iron correlated well with the second TEM pattern of deep lesions, whereas calcium with the third TEM pattern. No protein bands were detected on electrophoresis. Control lenses did not show any ultrastructural or chemical abnormality. CONCLUSIONS: The present study supports the presence of chemical alterations inside the polymer of the optic in late postoperative opacification of Hydroview IOLs. This opacification does not follow a unique pathway but may present under different ultrastructular patterns depending on the responsible factors. Mechanical stress during surgery may initiate a sequence of events where ions such as calcium, phosphorus, silicon, and/or iron, participate in a biochemical cascade that leads to gradual alteration of the polymer network. Intraocular inflammation due to previous operation may be a factor inducing opacification through increase of iron-binding capacity in the aqueous humour. Calcification accounts only partially for the opacification noted in this type of IOL.

IVIg dose increase in multifocal motor neuropathy: a prospective six month follow-up

In this prospective, non-randomized 6-month observational study we evaluated the efficacy of intravenous immunoglobulin (IVIg) dose increase in patients with multifocal motor neuropathy (MMN). Diagnosis according to AAEM criteria, repetitive IVIg treatment for at least one year, persistent paresis and conduction block, stable symptoms and findings for at least six months were inclusion criteria. Nine patients (7 men) were identified and approved to standardized increase of IVIg dose. Patients were monitored using clinical scores and electrophysiological studies. Dose was increased from a baseline of 0.5 g/kg per month [mean, range: 0.1-1.1], given at variable intervals [4-12 weeks] to 1.2 g/kg per month given over 3 consecutive days planned for 6 cycles. If the patients' motor function did not improve after two cycles they entered step two: Dose was increased to 2 g/kg per month given over 5 consecutive days. The increased dose was maintained for 6 months. Assessments were performed by the same investigator, not involved in the patient's management, at baseline, after 2 and after 6 months. Following dose increase, motor function significantly improved in 6 patients (p = 0.014), 2 patients entered step two, 1 patient withdrew due to absent efficacy. Higher doses of IVIg caused more side effects, however, transient and rarely severe (p = 0.014). IVIg dose increase may improve motor functions in patients with stable MMN on long-term IVIg therapy independent of baseline dose. Improvement of motor function was associated with shorter disease duration (p = 0.008), but not with degree of muscle atrophy (p = 0.483). The treatment strategy to try to find the lowest effective dose and the longest tolerated interval might lead to underdosing in the long-term in many patients.

Imaging of chronic recurrent multifocal osteomyelitis of childhood first presenting with isolated primary spinal involvement

OBJECTIVE: Initial presentation with primary spinal involvement in chronic recurrent multifocal osteomyelitis of childhood (CRMO) is rare. Our objective was to review the imaging appearances of three patients who had CRMO who initially presented with isolated primary spinal involvement. DESIGN AND PATIENTS: The imaging, clinical, laboratory and histology findings of the three patients were retrospectively reviewed. Imaging included seven spinal MR imaging scans, one computed tomography scan, nine bone scans, two tomograms and 16 radiographs. These were reviewed by two musculoskeletal radiologists and a consensus view is reported. All three patients presented with atraumatic spinal pain and had extensive bone spinal pathology. The patients were aged 11, 13 and 12 years. There were two females and one male. RESULTS AND CONCLUSIONS: The initial patient had thoracic T6 and T8 vertebra plana. Bone scan showed additional vertebral body involvement. Follow-up was available over a 3 year period. The second patient had partial collapse of T9 and, 2 years later, of C6. Subsequently extensive multifocal disease ensued and follow-up was available over 8 years. The third patient initially had L3 inferior partial collapse and 1 year later T8 involvement with multifocal disease. Follow-up was available over 3 years. The imaging findings of the three patients include partial and complete vertebra plana with a subchondral line adjacent to endplates associated with bone marrow MR signal alterations. Awareness of the imaging appearances may help the radiologist to include this entity in the differential diagnosis in children who present with spinal pathology and no history of trauma. Histopathological examination excludes tumor and infection but with typical imaging findings may not always be necessary.

Tunnelled versus straight intravitreal injection: intraocular pressure changes, vitreous reflux, and patient discomfort

PURPOSE: To compare tunnelled scleral intravitreal injection with straight scleral intravitreal injection concerning short-term intraocular pressure (IOP) changes, occurrence and amount of vitreous reflux, and patient discomfort. METHODS: Sixty patients were randomly allocated to two groups (tunnelled intravitreal injection and straight intravitreal injection). IOP was measured before and directly (<1 minute) after the injection of 0.05 mL of an antivascular endothelial growth factor agent and then every 5 minutes until IOP was <30 mmHg. Occurrence and amount of vitreous reflux were recorded. Patient discomfort during injection was assessed with a Wong-Baker faces pain rating scale. RESULTS: IOP (mmHg +/- SD) increased significantly directly after injection to 35.97 +/- 8.13 (tunnelled intravitreal injection) and 30.19 +/- 12.14 (straight intravitreal injection). These pressure spikes differed significantly between both groups (P = 0.01, mean difference: -7.11). Five minutes after injection, there was no significant difference in IOP increase between the groups. All IOP measurements were <30 mmHg after 15 minutes. Occurrence and amount of vitreous reflux were significantly higher with straight intravitreal injection. There was no significant difference in Wong-Baker faces pain rating scale score between both groups. CONCLUSION: Tunnelled intravitreal injection seems to be the technique of choice for low-volume intravitreal injection (0.05 mL). There is neither a difference in patient discomfort nor a difference in IOP increase 5 minutes after injection between both groups. Significantly less vitreous reflux with tunnelled intravitreal injection should lead to less postinjectional drug loss.

Incidence and outcome of progressive multifocal leukoencephalopathy over 20 years of the Swiss HIV Cohort Study

BACKGROUND: We investigated the incidence and outcome of progressive multifocal leukoencephalopathy (PML) in human immunodeficiency virus (HIV)-infected individuals before and after the introduction of combination antiretroviral therapy (cART) in 1996. METHODS: From 1988 through 2007, 226 cases of PML were reported to the Swiss HIV Cohort Study. By chart review, we confirmed 186 cases and recorded all-cause and PML-attributable mortality. For the survival analysis, 25 patients with postmortem diagnosis and 2 without CD4+ T cell counts were excluded, leaving a total of 159 patients (89 before 1996 and 70 during 1996-2007). RESULTS: The incidence rate of PML decreased from 0.24 cases per 100 patient-years (PY; 95% confidence interval [CI], 0.20-0.29 cases per 100 PY) before 1996 to 0.06 cases per 100 PY (95% CI, 0.04-0.10 cases per 100 PY) from 1996 onward. Patients who received a diagnosis before 1996 had a higher frequency of prior acquired immunodeficiency syndrome-defining conditions (P = .007) but similar CD4+ T cell counts (60 vs. 71 cells/microL; P = .25), compared with patients who received a diagnosis during 1996 or thereafter. The median time to PML-attributable death was 71 days (interquartile range, 44-140 days), compared with 90 days (interquartile range, 54-313 days) for all-cause mortality. The PML-attributable 1-year mortality rate decreased from 82.3 cases per 100 PY (95% CI, 58.8-115.1 cases per 100 PY) during the pre-cART era to 37.6 cases per 100 PY (95% CI, 23.4.-60.5 cases per 100 PY) during the cART era. In multivariate models, cART was the only factor associated with lower PML-attributable mortality (hazard ratio, 0.18; 95% CI, 0.07-0.50; P < .001), whereas all-cause mortality was associated with baseline CD4+ T cell count (hazard ratio per increase of 100 cells/microL, 0.52; 95% CI, 0.32-0.85; P = .010) and cART use (hazard ratio, 0.37; 95% CI, 0.19-0.75; P = .006). CONCLUSIONS: cART reduced the incidence and PML-attributable 1-year mortality, regardless of baseline CD4+ T cell count, whereas overall mortality was dependent on cART use and baseline CD4+ T cell count.

JC virus-specific immune responses in human immunodeficiency virus type 1 patients with progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a frequently fatal disease caused by uncontrolled polyomavirus JC (JCV) in severely immunodeficient patients. We investigated the JCV-specific cellular and humoral immunity in the Swiss HIV Cohort Study. We identified PML cases (n = 29), as well as three matched controls per case (n = 87), with prospectively cryopreserved peripheral blood mononuclear cells and plasma at diagnosis. Nested controls were matched according to age, gender, CD4(+) T-cell count, and decline. Survivors (n = 18) were defined as being alive for >1 year after diagnosis. Using gamma interferon enzyme-linked immunospot assays, we found that JCV-specific T-cell responses were lower in nonsurvivors than in their matched controls (P = 0.08), which was highly significant for laboratory- and histologically confirmed PML cases (P = 0.004). No difference was found between PML survivors and controls or for cytomegalovirus-specific T-cell responses. PML survivors showed significant increases in JCV-specific T cells (P = 0.04) and immunoglobulin G (IgG) responses (P = 0.005). IgG responses in survivors were positively correlated with CD4(+) T-cell counts (P = 0.049) and negatively with human immunodeficiency virus RNA loads (P = 0.03). We conclude that PML nonsurvivors had selectively impaired JCV-specific T-cell responses compared to CD4(+) T-cell-matched controls and failed to mount JCV-specific antibody responses. JCV-specific T-cell and IgG responses may serve as prognostic markers for patients at risk.

Multifocal posterior uveitis in Crohn's disease

PURPOSE To report a case of rare posterior eye manifestation of Crohn's disease preceding recurrence of inflammatory bowel disease. METHODS Case report with ophthalmoscopic findings, fluorescein/indocyanin green angiograms, automated perimetry and multifocal-ERG. RESULTS The perimetry revealed absolute and relative scotomas corresponding to multifocal inflammatory lesions in the retina and choroid, reduced a/b amplitudes in multifocal-ERG and hypofluorescent dots in angiography. Under oral prednisolone visual defects, ophthalmoscopic and angiographic findings resolved, while a/b amplitudes remained mildly reduced. The ocular changes occurred without systemic hypertension and were followed by a new episode of intestinal symptoms. CONCLUSION Multifocal inflammatory lesions in the retina and choroid in patients with Crohn's disease may occur and may precede a recurrent intestinal episode. Crohn's patients should be carefully followed up in collaboration with internal medicine specialists.

Taking Digital Microphotography and Videos through a Microscope without any Special Lens

Introduction: Photography through a microscope is virtually identical to that used with an astronomical telescope. For years, the 35mm camera was the choice for microphotography, but we live in a digital camera age now. We describe a custom homemade adapter that can be fit most of the cameras and microscopes. [See PDF for complete abstract]

Progressive multifocal leukoencephalopathy in a patient without apparent immunosuppression.

An 80-year-old man with no history of an immune-compromising disorder was diagnosed with progressive multifocal leukoencephalopathy (PML). He presented with dysphagia and left-sided weakness; magnetic resonance imaging demonstrated marked signal abnormality in the subcortical white matter of the left frontal lobe and in the posterior limb of the right internal capsule. Polymerase chain reaction (PCR) analysis of the cerebrospinal fluid (CSF) was negative for John Cunningham (JC) virus. On brain biopsy, foamy macrophages infiltrating the white matter were identified, staining positive for anti-simian virus 40 antibodies. Postoperatively, PCR for JC viral DNA in the CSF was positive, establishing the diagnosis of PML. Extensive investigation for an occult immunocompromising disorder was negative. The patient's neurologic deficits rapidly increased throughout his hospital stay, and he died 3.5 months after his diagnosis.

Sanitation in developing countries: A review through a gender lens

Sanitation has evolved from a purely technical discipline to one that includes social, environmental, economic and, increasingly, gender considerations. However, blurry notions of gender are frequently offered in the sanitation literature. Although it has been recognized that gender-responsive sanitation does not mean ‘toilets for women’, substantial alternatives are rarely debated. We structure our review of sanitation in developing countries along three lines: we start by fine-tuning the concept of gender both from the academic and the practitioner's perspective, analyse relevant developments in gender-specific policies and programming, and finally review the most appropriate toilet room and menstrual hygiene technologies. We argue that strategies to make technologies gender-responsive need to be based upon a thorough analysis of the social arrangements of the intimate, and how these are negotiated and institutionalized in a specific context. A lack of robust gender-segregated data on sanitation policies and technologies, along with reductionist framings of gender are to blame for limited progress in verifying the need for, and impact of, gender-responsive sanitation. Technology and policy development and implementation would benefit from gender-considerate interpretations of shame, dignity, safety and status. Further progress could be achieved by improving the translation process between different academic framings of the sanitation crisis. Keywords: appropriate technology; development; gender; menstrual hygiene management (MHM); sanitation

Noninvasive referencing of intraocular tumors for external beam radiation therapy using optical coherence tomography: a proof of concept.

PURPOSE External beam radiation therapy is currently considered the most common treatment modality for intraocular tumors. Localization of the tumor and efficient compensation of tumor misalignment with respect to the radiation beam are crucial. According to the state of the art procedure, localization of the target volume is indirectly performed by the invasive surgical implantation of radiopaque clips or is limited to positioning the head using stereoscopic radiographies. This work represents a proof-of-concept for direct and noninvasive tumor referencing based on anterior eye topography acquired using optical coherence tomography (OCT). METHODS A prototype of a head-mounted device has been developed for automatic monitoring of tumor position and orientation in the isocentric reference frame for LINAC based treatment of intraocular tumors. Noninvasive tumor referencing is performed with six degrees of freedom based on anterior eye topography acquired using OCT and registration of a statistical eye model. The proposed prototype was tested based on enucleated pig eyes and registration accuracy was measured by comparison of the resulting transformation with tilt and torsion angles manually induced using a custom-made test bench. RESULTS Validation based on 12 enucleated pig eyes revealed an overall average registration error of 0.26 ± 0.08° in 87 ± 0.7 ms for tilting and 0.52 ± 0.03° in 94 ± 1.4 ms for torsion. Furthermore, dependency of sampling density on mean registration error was quantitatively assessed. CONCLUSIONS The tumor referencing method presented in combination with the statistical eye model introduced in the past has the potential to enable noninvasive treatment and may improve quality, efficacy, and flexibility of external beam radiotherapy of intraocular tumors.

Developing Psychosis and Its Risk States Through the Lens of Schizotypy

Starting from the early descriptions of Kraepelin and Bleuler, the construct of schizotypy was developed from observations of aberrations in nonpsychotic family members of schizophrenia patients. In contemporary diagnostic manuals, the positive symptoms of schizotypal personality disorder were included in the ultra high-risk (UHR) criteria 20 years ago, and nowadays are broadly employed in clinical early detection of psychosis. The schizotypy construct, now dissociated from strict familial risk, also informed research on the liability to develop any psychotic disorder, and in particular schizophrenia-spectrum disorders, even outside clinical settings. Against the historical background of schizotypy it is surprising that evidence from longitudinal studies linking schizotypy, UHR, and conversion to psychosis has only recently emerged; and it still remains unclear how schizotypy may be positioned in high-risk research. Following a comprehensive literature search, we review 18 prospective studies on 15 samples examining the evidence for a link between trait schizotypy and conversion to psychosis in 4 different types of samples: general population, clinical risk samples according to UHR and/or basic symptom criteria, genetic (familial) risk, and clinical samples at-risk for a nonpsychotic schizophrenia-spectrum diagnosis. These prospective studies underline the value of schizotypy in high-risk research, but also point to the lack of evidence needed to better define the position of the construct of schizotypy within a developmental psychopathology perspective of emerging psychosis and schizophrenia-spectrum disorders