Confocal microscopy and corneal sensitivity in a patient with corneal manifestations of Tangier disease

PURPOSE: Tangier disease is an autosomal recessive disorder in which cholesterol-rich lipids are deposited at various tissues of the body including the cornea. In this case report, the corneal changes in a patient with Tangier disease are described. METHODS: A 72-year-old patient who was diagnosed with Tangier disease 25 years before received a complete eye examination including confocal microscopy and Cochet-Bonnet esthesiometry. RESULTS: Slit-lamp biomicroscopy and confocal microscopy showed bilateral corneal opacifications caused by lipid accumulation. Confocal microscopy showed that pathologic changes in the cornea in Tangier disease are limited to the stroma. Neither a reduced corneal sensation nor lid abnormalities as previously described in Tangier disease were found. CONCLUSION: Confocal microscopy helps to identify corneal changes in the stroma caused by Tangier disease easily missed in a slit-lamp examination. The ocular manifestations of Tangier disease do not necessarily include a reduced corneal sensitivity and lid abnormalities.     

Dependency of polychlorinated biphenyl and polycyclic aromatic hydrocarbon bioaccumulation in Mya arenaria on both water column and sediment bed chemical activities

The bioaccumulation of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) by the filter-feeding soft-shell clam Mya arenaria was evaluated at three sites near Boston (MA, USA) by assessing the chemical activities of those hydrophobic organic compounds (HOCs) in the sediment bed, water column, and organisms. Polyethylene samplers were deployed to measure the activities of HOCs in the water column. Sediment activities were assessed by normalizing concentrations with sediment-water sorption coefficient values, including adsorption to black carbon in addition to absorption by organic carbon. Likewise, both lipids and proteins were considered in biota-water partition coefficients used to estimate chemical activities in the animals. Chemical activities of PAHs in M. arenaria were substantially less than those of the corresponding bed sediments in which they lived. In contrast, chemical activities of PCBs in M. arenaria often were greater than or equal to activities in the corresponding bed sediments. Activities of PAHs, such those of pyrene, in the water column were undersaturated relative to the sediment. However, some PCBs, such as congener 52, had higher activities in the water column than in the sediment. Tissue activities of pyrene generally were in between the sediment and water column activities, whereas activity of PCB congener 52 was nearest to water column activities. These results suggest that attempts to estimate bioaccumulation by benthic organisms should include interactions with both the bed sediment and the water column.     

Ventricular rate stabilization for the prevention of pause dependent ventricular tachyarrhythmias: results from a prospective study in 309 ICD recipients

Reviews of stored electrograms from ICDs revealed a 5-30% incidence of short-long-short intervals preceding the onset of recurrent ventricular tachyarrhythmias. Rate stabilization by dedicated antibradycardia pacing algorithms has, therefore, been suggested to prevent onset of pause dependent tachyarrhythmias. However, the clinical efficacy of this approach has not been studied systematically. In a prospective multicenter crossover study, patients were randomized to activation or deactivation of an implemented ventricular rate stabilization algorithm (VRS) after first implant of a dual chamber ICD. After 3 months, all patients were crossed over to the alternate programming. The rate of appropriate spontaneous VA episodes was compared between VRS On and VRS Off. Stored electrograms were reviewed for evaluation of the mode of onset of tachyarrhythmias. Overall efficacy analysis was based on 309 patients enrolled in the study. Forty percent (124/309) of the patients experienced 4,973 VA episodes. Based on an intention-to-treat analysis, VRS Off and On arrhythmia incidence was 10.2 and 6.6 normalized to 3 months, respectively (risk reduction 35%; P = 0.18) On an on-treatment basis, a reduction from 9.0 episodes to 8.1 episodes (10% risk reduction, P = 0.24) was seen. In an extended Cox model adjusting for confounding variables, the relative risk for recurrent episodes was 0.92 during VRS On compared to Off (95% CI: 0.58-1.48; P = 0.74). During VRS Off, pause dependent onset was documented in only 36 (8%) of 427 visually analyzed episodes. There was no significant reduction in the incidence of recurrent ventricular tachyarrhythmias with VRS On compared to the Off programming in this prospective study.     

Survival in second primary malignancies of patients with head and neck cancer

Second primary tumours occur frequently in patients with a history of head and neck malignancies. Delays in making an early and correct diagnosis can seriously affect the therapy management and survival. This was a retrospective study of 120 patients with a history of head and neck cancer, presenting with a second primary tumour. Current follow-up strategies and the use of routine sonographic imaging of the head and neck regions were evaluated, and the impact that tumour chronology, the tumour site and the various treatment modalities have on the survival were assessed. Forty-two per cent of patients developed a metachronous second malignancy more than five years after diagnosis of the index tumour. The accuracy of colour-duplex sonography in detection of second primaries in the head and neck was 82.3 per cent. First and second primary tumours located in the larynx were observed to have the highest five-year survival rate. Patients who developed metachronous tumours had a five-year survival rate of 68.9 per cent for the index tumours, and a 26 per cent five-year survival rate with the occurrence of a second neoplasm. With synchronous tumours a mean survival time of 18 months and a five-year survival rate of 11.9 per cent was found (p < 0.0001). Where clinically appropriate an aggressive treatment strategy was employed and yielded the most favourable results with a five-year survival rate of 66.8 per cent and 35.9 per cent for index tumours and second primary malignancies, respectively. Since more than 40 per cent of the metachronous second primaries in patients with a history of head and neck malignancy occur beyond the five-year follow-up period, an extended protocol with individually adjusted close monitoring of high-risk patients seems appropriate. Colour-duplex sonography is a valuable screening investigation for the early detection of second primary tumours. The treatment of a second primary is often less successful than for the same malignancy occurring primarily. The prognosis of synchronous tumours is significantly lower when compared to malignancies of a metachronous nature, despite some encouraging individual results. Only the early implementation of aggressive treatment methods for second primaries is successful in terms of survival.     

Optical biometry before and after excimer laser epithelial keratomileusis (LASEK) for myopia

PURPOSE: In order to select the correct intraocular lens (IOL) for implantation, it is important to measure the eye length (biometry). The IOL Master from Zeiss-Humphry is frequently used for such measurements. Because this instrument employs an optical method, any irregularities on the corneal surface or any disturbances in corneal transparency could lead to mistakes in the measurements. The aim of this study was to determine whether eye length measurements obtained at the University Eye Clinic Regensburg, Germany with the IOL Master before and after excimer laser epithelial keratomileusis (LASEK) show any changes. METHODS: Axial length was measured on 20 myopic eyes (-2.75 to -8.00 diopters) before and one month after LASEK using the IOL Master. RESULTS: The mean pre-operative eye length was 25.46 mm (SD +/- 1.03) and the post-operative mean length was 25.38 mm (SD +/- 0.99). There was a strong correlation between the pre- and post-operative eye lengths (Pearson correlation coefficient 0.998). CONCLUSIONS: Although LASEK can lead to increased light scattering due to irregularities of the corneal surface and changes in corneal transparency, there is no difference in biometry pre- and post-operatively.     

Tumor classification based on gene expression profiling shows that uveal melanomas with and without monosomy 3 represent two distinct entities

Uveal melanoma is the most common intraocular malignancy. About 50% of patients die of metastases, which almost exclusively originate from primary tumors that have lost one chromosome 3 (monosomy 3). To gain insight into the biological mechanisms that underlie the various metastasizing potential of uveal melanoma, we have determined gene expression levels in 20 primary tumors using oligonucleotide microarrays containing 12500 probe sets. The expression measurements of those 7902 genes that were expressed in more than 10% of tumors were analyzed using two different statistical approaches. We used a modified Wilcoxon rank-sum test to identify genes differentially expressed between tumors with and without monosomy 3. Seven genes showed complete loss of expression in tumors with monosomy 3 but were expressed in tumors with disomy 3. Two of them, CHL1 and fls485, are located within or close to the uveal melanoma susceptibility locus UVM2 at 3p25. However, mutation analysis of both genes in eight tumors with monosomy 3 did not reveal structural or epigenetic alteration. To identify tumor classes, we performed unsupervised hierarchical cluster analysis; this approach separated uveal melanomas into two groups. We found that this classification is strikingly robust because, when tested by "resampling," the same grouping is obtained from 47 of 50 subsamples of genes. In clusterings of the three remaining subsamples, the grouping of only one tumor does not conform with the original classification. Excluding this tumor, cluster analyses of subsamples containing as few as 300 randomly chosen genes consistently result in the same classification, thus indicating that the difference between the two tumor classes is pervasive. Interestingly, all of the tumors in one of the groups have disomy 3, whereas all of the others have monosomy 3. Our findings suggest that there are two distinct entities of uveal melanoma that were previously unrecognized because they are not obviously distinguishable by clinicopathological features.     

Primary malignant melanoma of the oesophagus: a clinical and pathological study with emphasis on the immunophenotype of the tumours for melanocyte differentiation markers and cancer/testis antigens

SUMMARY: Primary malignant melanomas of the oesophageal squamous mucosa are exceedingly rare. We present here the clinical and pathological findings of 10 patients (mean age 64 years) with primary oesophageal melanoma, with emphasis on the immunophenotype of the tumours. The majority of melanomas were located in the mid to distal oesophagus and were large (mean tumour size at the time of diagnosis 6.2 cm; mean depth of invasion 1.86 cm). All but two of the melanomas were associated with an extensive in situ component. Half of the tumours were amelanotic. The histological spectrum was wide, including appearances mimicking lymphoma, poorly differentiated adenocarcinoma or sarcoma. Immunohistochemical studies were performed on six tumours using monoclonal antibodies (MAb) to S100 protein, tyrosinase (MAb T311), Melan-A (MAb A103), and gp100 (MAb HMB-45), as well as antibodies to five cancer/testis (CT) antigens (MAb CT7-33 to CT7/MAGE-C1, MAb ESO121 to NY-ESO-1, MAb 57B to MAGE-A4, MAb MA454 to MAGE-A1, and MAb M3H67 to MAGE-A3). Seven patients had metastatic disease at the time of presentation. All but one patient underwent resection of the tumour with negative surgical margins. Survival was poor, with a mean survival of 19.8 months. One patient, however, whose tumour was limited to the submucosa, is still alive 108 months post-oesophagectomy. All six melanomas examined by immunohistochemistry were positive for all the melanocyte differentiation markers tested. In addition, they were all positive for CT antigens, with MA454 being the most commonly found, suggesting that CT antigens may be a promising immunotherapeutic target for oesophageal melanomas.     

In vitro studies indicate that miquelianin (quercetin 3-O-beta-D-glucuronopyranoside) is able to reach the CNS from the small intestine

Miquelianin (quercetin 3-O-beta-D-glucuronopyranoside) is one of the flavonoids of St. John's wort (Hypericum perforatum L.) whose antidepressant activity has been shown by the forced swimming test, an in vivo pharmacological model with rats. However, nothing is known about its ability to reach the CNS after oral administration. We examined the pathway of miquelianin from the small intestine to the central nervous system using three in vitro membrane barrier cell systems. In the Caco-2 cell line, miquelianin showed a higher uptake (1.93 +/- 0.9 pmol x min(-1) x cm(-2)) than hyperoside (quercetin 3-O-beta-D-galactopyranoside; 0.55 +/- 0.18 pmol x min(-1) x cm(-2)) and quercitrin (quercetin 3-O-alpha-L-rhamnopyranoside; 0.22 +/- 0.08 pmol x min(-1) x cm(-2)). The permeability coefficient of miquelianin (Pc = 0.4 +/- 0.19 x 10(-6) cm/sec) was in the range of orally available drugs assuming sufficient absorption from the small intestine. Uptake and permeability of the examined compounds was increased by the MRP-2 inhibitor MK-571 indicating a backwards transport by this membrane protein. Porcine cell cultures of brain capillary endothelial cells were used as a model of the blood-brain barrier (bbb) and epithelial cells of the plexus chorioidei as a model of the blood-CSF barrier (bcb). Results indicate no active transport in one direction. Although moderate, the permeability coefficients (bbb: Pc = 1.34 +/- 0.05 x 10(-6) cm/sec; bcb: Pc = 2.0 +/- 0.33 x 10(-6) cm/sec) indicate the ability of miquelianin to cross both barriers to finally reach the CNS.