Cataract Surgery in HIV Seropositive Patients: Long-Term Follow-Up

Purpose: To study epidemiology and clinical findings of cataract in HIV+ patients.

Methods: A total of 32 HIV+ patients, 11 with uveitis/retinitis before surgery and 21 without, mean follow-up 44.9 ± 36.6 months, and 114 HIV- patients, 57 with uveitis/retinitis before surgery and 57 without, were retrospectively compared.

Results: Visual acuity improved in all HIV+ patients (p < 0.001), who were younger (p = 0.01) and more frequently males (p = 0.027). HIV+ patients with uveitis prior surgery improved less (p = 0.046) than HIV- (p < 0.001); their anterior chamber inflammation was similar to baseline. Male sex (p = 0.005), younger age (p < 0.001), dyslipidaemia (p = 0.058), HBV+ (p = 0.037), and unilateral cataract (p = 0.001) were more frequent in HIV+ patients with senile cataract, but they showed the same postoperative course as HIV- patients.

Conclusion: Cataract surgery in HIV+ patients is safe and effective. Uveitis prior to surgery did not significantly affect the postoperative course. Systemic comorbidities are more frequent in HIV+ patients with senile cataract than in HIV- subjects.     

Evaluation of <i>MGMT</i> Gene Methylation in Neuroendocrine Neoplasms

Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O6 -methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in welldifferentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.     

Human antibody against C domain of tenascin-C visualizes murine atherosclerotic plaques ex vivo.

Targeting proteins that are overexpressed in atherosclerotic plaques may open novel diagnostic applications. The C domain of tenascin-C is absent from normal adult tissues but can be inserted during tumor progression or tissue repair into the molecule by alternative splicing. We tested the ability of the human antibody G11, specific to this antigen, to reveal murine atherosclerotic plaques ex vivo. The antibody directed against the extra domain B of fibronectin (L19) was used as a reference. METHODS: We intravenously injected (125)I-labeled G11 or L19 antibodies into apolipoprotein E-deficient (ApoE(-/-)) mice and harvested the aortae 4 or 24 h later. En face analyses of distal aortae and longitudinal sections of the aortic arch were performed to compare antibody uptake using autoradiography with plaque staining using oil red O. Plaque macrophages were detected by immunohistochemistry (anti-CD68 staining). Biodistribution of injected antibodies was investigated in aortae and blood at 4 and 24 h. RESULTS: En face analyses revealed a significant correlation between radiolabeled G11 and fat-stained areas, increasing from 4 to 24 h, with a correlation coefficient of 0.92 (P < 0.0001) and an average signal-to-noise ratio of 104:1 at 24 h. Plaque imaging using L19 showed similar results (r = 0.86; P < 0.0001; signal-to-noise ratio, 72:1 at 24 h). Uptake of radiolabeled antibodies in histologic sections colocalized with fat staining and activated macrophages in aortic plaques. Biodistribution analyses confirmed specific accumulation in aortic plaques as well as rapid blood pool clearance of the antibodies 24 h after injection. Immunofluorescence analyses revealed increased expression of tenascin and fibronectin isoforms in macrophage-rich plaques. CONCLUSION: The antibody G11, specific to the C domain of tenascin-C, visualizes murine atherosclerotic plaques ex vivo. In conjunction with the increased expression of the C domain of tenascin-C in macrophage-rich plaques, the colocalization of G11 uptake with activated macrophages, and the favorable target-to-blood ratio at 24 h, this antibody may be useful for molecular imaging of advanced atherosclerotic plaques in the intact organism.     

Taylor-type focal cortical dysplasia: is the epilepsy always resistant to medical treatment?

Patients with Taylor-type focal cortical dysplasia (TTFCD) generally present with medically intractable epilepsy and impaired neurological and/or intellectual functioning. Surgery usually proves to be the only treatment approach leading to control of seizures. We describe a 17-year-old girl with TTFCD who exhibited a very long period of seizure remission. Combined clinical and neuroimaging findings were compatible with a diagnosis of a balloon cell-subtype TTFCD. As for the clinical course, partial motor seizures began at one year of age and ceased at five: our patient has had no seizure recurrence over a 12-year-follow-up. Moreover, throughout the 15-year follow-up, neurological examinations and cognitive abilities always remained within normal limits. Neuropsychological assessment clearly showed no impairments in executive functions: planning abilities, working memory, attention and impulse control, or constructive aspects of motor coordination. The predominant deficits pertained to verbal abilities in the context of borderline intellectual performances. To our knowledge, this case report documents the longest duration of seizure remission in a patient with TTFCD, thus emphasizing the possible benign course of such dysplastic lesions which usually have a poor prognosis, leading to early surgical treatment.     

Cavernous angiomas of the spinal district: surgical treatment of 11 patients

Cavernous angiomas, also called cavernous malformations or cavernomas, are vascular hamartomas accounting for 3–16% of all angiomatous lesions of the spinal district. Although histologically identical, these vascular anomalies may exhibit different clinical behavior and radiological features, depending on their location, hinting at different managements and therapeutic approaches. The authors report 11 cases of symptomatic spinal cavernous angiomas diagnosed and surgically treated over the past 18 years. Age of patients ranged from 15–75 years; males outnumbered females. Three patients had vertebral cavernous malformations, secondarily invading the epidural space; two had pure epidural lesions; two patients had intradural extramedullary lesions, and four intramedullary lesions. Surgical removal was completely achieved in four patients with intramedullary lesions, in two with subdural extramedullary lesions, and in one with a pure epidural lesion. Subtotal excision of another one epidural and three vertebral cavernous angiomas was followed by radiotherapy. There was no morbidity related to surgery; the mean follow-up was 2 years. The outcome was excellent in two cases, good in six, and unchanged in the other three. The authors discuss the different modalities of treatment of these vascular lesions variously placed along the spine.     

Comparison of self-reports and biological measures for alcohol, tobacco, and illicit drugs consumption in psychiatric inpatients

BACKGROUND: Asking psychiatric in-patients about their drug consumption is unlikely to yield reliable results, particularly where alcohol and illicit drug use is involved. The main aim of this study was to compare spontaneous self-reports of drug use in hospitalized psychiatric patients to biological measures of same. A secondary aim was to determine which personal factors were associated with the use of tobacco, alcohol, and illicit drugs as indicated by these biological measures. METHODS: The consumption of substances was investigated using biological measures (urine cotinine, cannabis, opiates, cocaine, amphetamines and barbiturates; blood carbohydrate-deficient transferrin [CDT] and gamma-glutamyl transferase [GGT]) in 486 consecutively admitted psychiatric patients, one day following their hospitalization. Patients' self-reports of alcohol, tobacco and illicit drugs consumption were recorded. Socio-professional and familial data were also recorded. RESULTS: The results show a low correlation between biological measures and self-reported consumption of alcohol and illicit drugs. Fifty-two percent of the patients under-reported their consumption of illicit drugs (kappa=.47). Patients with schizophrenia and personality disorders were more likely to disclose their illicit drug consumption relative to patients suffering from mood disorders and alcohol dependence. Fifty-six percent of patients underreported alcohol use, as evaluated by CDT (kappa=.2), and 37% underreported when using the CDT+GGT measure as an indicator. Smoking appeared to be reported adequately. In the study we observed a strong negative correlation between cannabis use and age, a strong correlation between tobacco and cannabis use, and correlations between tobacco, cannabis and alcohol consumption. CONCLUSION: This study is the first to compare self-reports and biological measures of alcohol, tobacco and illicit drug uses in a large sample of inpatients suffering from various categories of psychiatric illnesses, allowing for cross-diagnosis comparisons.