Structural and functional changes associated with normal and abnormal fundus autofluorescence in patients with retinitis pigmentosa.

PURPOSE: To analyze the structure and visual function of regions bordering the hyperautofluorescent ring/arcs in retinitis pigmentosa. METHODS: Twenty-one retinitis pigmentosa patients (21 eyes) with rings/arcs and 21 normal individuals (21 eyes) were studied. Visual sensitivity in the central 10° was measured with microperimetry. Retinal structure was evaluated with spectral-domain optical coherence tomography. The distance from the fovea to disruption/loss of the inner outer segment (IS/OS) junction and thicknesses of the total receptor plus retinal pigment epithelial complex and outer segment plus retinal pigment epithelial complex layers were measured. Results were compared with measurements of the distance from the fovea to the inner and outer borders of the ring/arc seen on fundus autofluorescence. RESULTS: Disruption/loss of the inner outer segment junction occurred closer to the inner border of the ring/arc and it was closer to the fovea in eight eyes. For 19 eyes, outer segment plus and receptor plus RPE complex thicknesses were significantly decreased at locations closer to the fovea than the appearance of the inner border of hyperautofluorescence. Mean visual sensitivity was decreased inside, across, and outside the ring/arc by 3.5 ± 3.8, 8.9 ± 4.8, and 17.0 ± 2.4 dB, respectively. CONCLUSION: Structural and functional changes can occur inside the hyperfluorescent ring/arc in retinitis pigmentosa.

Histologic evaluation of an Nd:YAG laser-assisted new attachment procedure in humans.

This report presents histologic results in humans following a laser-assisted new attachment procedure (LANAP) for the treatment of periodontal pockets. Six pairs of single-rooted teeth with moderate to advanced chronic periodontitis associated with subgingival calculus deposits were treated. A bur notch was placed within the pocket at the clinically and radiographically measured apical extent of calculus. All teeth were scaled and root planed with ultrasonic and hand scalers. One of each pair of teeth received treatment of the inner pocket wall with a free-running pulsed neodymium:yttrium-aluminum-garnet (Nd:YAG) laser to remove the pocket epithelium, and the test pockets were lased a second time to seal the pocket. After 3 months, all treated teeth were removed en bloc for histologic processing. LANAP-treated teeth exhibited greater probing depth reductions and clinical probing attachment level gains than the control teeth. All LANAP-treated specimens showed new cementum and new connective tissue attachment in and occasionally coronal to the notch, whereas five of the six control teeth had a long junctional epithelium with no evidence of new attachment or regeneration. There was no evidence of any adverse histologic changes around the LANAP specimens. These cases support the concept that LANAP can be associated with cementum-mediated new connective tissue attachment and apparent periodontal regeneration of diseased root surfaces in humans.

A rare case of unifocal, unilateral pigmented paravenous retinochoroidal atrophy (PPRCA).

PURPOSE: To report an atypical case of unifocal, unilateral pigmented paravenous retinochoroidal atrophy (PPRCA) characterized by thickening and cystic degeneration of the retinal nerve fiber layer (RNFL). OBSERVATIONS: A 79-year old Asian woman presented with a large area of atrophic, pigmented change along the inferior arcade of her right eye. She denied nyctalopia and any other visual complaints. Visual acuity was 20/40 in both eyes and visual fields were significant for a large absolute peripheral scotoma superiorly in the affected eye corresponding to the atrophic area. Spectral domain optical coherence tomography through the lesion showed loss of choroid except for largest Haller's layer vessels, significant retinal pigment epithelium atrophy with migration and pigment clumping, outer retinal layer loss and RNFL thickening with cystic degeneration. Fundus autofluorescence imaging showed a large area of hypoautofluorescence corresponding to the area of atrophy. Full field electroretinogram demonstrated normal scotopic response and reduced photopic response in the right eye. CONCLUSIONS AND IMPORTANCE: PPRCA is typically bilateral and symmetric, affecting primarily the outer retina and choroid. However, in rare cases, this disease can present unilaterally and/or unifocally, with degeneration extending to the inner retinal layers.

Rod and cone photoreceptor function in patients with cone dystrophy.

PURPOSE: To determine the extent of rod and cone photoreceptor dysfunction in patients with cone dystrophy using psychophysical and electrophysiological tests. METHODS: Ten patients with cone dystrophy participated. Rod and cone system psychophysical thresholds were measured as a function of retinal eccentricity. Bright-flash full-field electroretinograms were obtained under dark-adapted (rod-mediated) and light-adapted (cone-mediated) conditions. The a-wave data were fitted with a model based on photopigment transduction to obtain values for log Rmax (maximum response) and log S (sensitivity). b-Wave parameters were also examined by fitting a nonlinear, saturating function (the Naka-Rushton equation) to the rod-mediated responses. Oscillatory potentials were measured to the cone-mediated high-intensity flashes. RESULTS: On average, the rod-mediated psychophysical thresholds were elevated by 0.5 log unit. These threshold elevations did not differ significantly with retinal eccentricity. In contrast, cone-mediated psychophysical thresholds were elevated up to 3.0 log units. Threshold elevation was greatest in the central retinal locations. For rod-mediated conditions, the a-wave Rmax parameter was significantly reduced in three patients; the a-wave log S parameter was within normal limits. The rod-mediated b-wave Rmax parameter was reduced in six patients; log k was abnormal in one patient. For cone-mediated conditions, the a-wave Rmax parameter was reduced in six patients and the a-wave log S parameter was reduced in two patients. The cone system oscillatory potentials were abnormal in nine patients. CONCLUSIONS: Patients with cone dystrophy show different patterns of psychophysical rod versus cone system sensitivity losses with retinal eccentricity. The full-field electrophysiological data indicate that most of the patients had abnormal cone photoreceptor function. Some patients also showed rod photoreceptor abnormalities. The rod system changes were smaller than the cone system changes.

Local cone and rod system function in progressive cone dystrophy.

PURPOSE: To compare the patterns of local cone and rod system impairment in patients with progressive cone dystrophy (CD) using psychophysical and electrophysiological techniques. METHODS: Local cone system function was assessed by measuring cone system thresholds (visual fields) and cone-mediated multifocal electroretinograms (mfERGs). Rod system function was assessed by measuring rod system thresholds (visual fields) and rod-mediated mfERGs. The results in a group of eight patients with CD were compared with those in an age-similar control group. RESULTS: All the patients had abnormal cone system visual field thresholds and cone-mediated mfERGs. Cone system psychophysical thresholds were elevated for targets presented within the central 10 degrees, but were within normal limits for targets at peripheral locations. Cone-mediated mfERG measures of amplitude scale and time scale were abnormal for most of the hexagons tested. Most of the rod-mediated psychophysical thresholds and mfERGs were within normal limits. Rod system losses tended to be patchy and scattered throughout the area tested. CONCLUSIONS: There was poor correspondence among local measures of cone and rod system losses in these patients with CD. The results suggest that the spatial pattern of cone system losses in this disease differs from the spatial pattern of rod system losses.

Multifocal electroretinography as a function of age: the importance of normative values for older adults.

PURPOSE: To determine the influence of age on local electroretinographic responses in humans. METHODS: Multifocal electroretinograms (mfERGs) were obtained from 62 normally sighted subjects ranging in age from 21 to 81 years. A stimulus array of 103 scaled hexagons was used to measure electrical signals within a retinal area approximately 46 degrees in diameter. Commonly reported mfERG methods were used to quantify the responses: peak-to-peak amplitudes and implicit times, scalar product amplitude, and amplitude and time scales derived from the algorithm of Hood and Li, published in 1997. RESULTS: Regression analysis showed significant linear relationships of amplitude and timing measures with age. The rates of losses were 10.5% per decade for peak-to-peak amplitude, 11.7% per decade for scalar product amplitude, and 9.5% per decade for a-scale. The rate of amplitude reduction was highest in the central 3 degrees. Age had less influence on implicit time measures. The rates of timing losses were 1.4% per decade for the N1 component and 1.0% per decade for both the P1 component and the t-scale measure. Using predicted interval ranges, the age was calculated at which 50% of the expected values would fall below the lower 95% prediction interval band of younger subjects. CONCLUSIONS: The age-associated mfERG alterations are presented to emphasize the importance of appropriate normative data in interpretation of mfERGs.

A method for comparing psychophysical and multifocal electroretinographic increment thresholds.

The multifocal electroretinogram (mfERG) has been commonly used as a method for obtaining objective visual fields. Although qualitative comparisons have been good, quantitative comparisons between the results from mfERG and the results from Humphrey Visual Field Analyser (HVFA) have found variable degrees of agreement depending upon the mfERG response parameter examined and/or the disease studied. Lack of agreement may be due to differences in methodology, differences in the sites of response generation, and/or differences derived from comparing suprathreshold versus threshold responses. In addition, the two procedures are performed at different levels of adaptation. We developed an approach for matching stimulus parameters and compared mfERG and psychophysical thresholds to assess the effects of technique and level of adaptation on the two responses. Psychophysical and mfERG thresholds were obtained as a function of the adaptation level (1.5-4.0 log td) and retinal location. The derived increment threshold-versus-intensity functions for both measures were fitted using the equation logT=logT(0)+log((A+A(0))/A(0))(n). We found that the values of A(0) for the mfERG data were one log unit higher than those for the psychophysical data. In addition, the value of the slope (n) for the mfERG data was shallower (0.8) than that of the psychophysical data (1.0). Predictions were made about comparisons of HVFA threshold and mfERG amplitude data in patients with retinal disease based upon a two-site model of adaptation. The data for some groups of patients could be best-fitted with a model of a disease acting at a site distal to all gain changes, whereas data from other patients were best fitted with a model of a disease acting at a site proximal to all retinal gain. The relationship between the Humphrey visual field threshold losses and mfERG amplitude reductions depends upon the site and mechanism of a particular disease process and the model of retinal gain assumed. In no case is a one-to-one relationship between the losses in the two measures predicted.

Adenoid ameloblastoma with dentinoid: a case report.

A man had a lesion of the anterior mandible that was initially diagnosed at 39 years of age as an adenomatoid odontogenic tumor. The lesion recurred 3 times over a span of 16 years. A consultative review of all histological findings was done and the tumor was reclassified as an ameloblastoma.

The central granular cell odontogenic tumor: report of 5 new cases.

This article reports 5 previously unreported cases of central granular cell odontogenic tumor and compares them with 25 cases from the literature. This lesion appears to be an uncommon benign odontogenic neoplasm of uncertain histogenesis; it occurs over a wide age range with a predilection for the mandibular premolar-molar region. Radiographically, it typically manifests as a well-defined unicystic or multilocular radiolucency, although it can be a mixed-density lesion as well. In our series, there was a narrow spectrum of histologic features consisting of fibrous tissue of altering density and cellularity with plentiful numbers of large eosinophilic granular cells, variable amounts of "inactive-appearing" odontogenic epithelium, and the variable presence of calcified tissue resembling cementum or dystrophic calcifications. The ultrastructural and immunohistochemical findings in this study support a mesenchymal origin for the granular cells. One recurrence was documented in the current series in contrast to no recurrences in the literature.

Periodontal regeneration following use of ABM/P-1 5: a case report.

ABM/P-15 is a combination of a natural anorganic bovine-derived hydroxyapatite matrix (ABM) and a synthetic cell-binding peptide (P- 15; PepGen P- 15) that has shown the capacity to encourage substantial clinical fill of periodontal infrabony defects. Human histology following its use has not been evaluated on pathologic root surfaces. A maxillary lateral incisor with advanced adult periodontitis that was treatment planned for extraction was treated with sulcular incisions, full-thickness flap reflection, debridement of granulomatous tissue from the defect, placement of a notch in the root at the apical extent of calculus, mechanical root planing, brief cleansing with citric acid, grafting with ABM/P-15, wound closure with sutures, and placement of a periodontal dressing. Biweekly to monthly recalls were made until removal of a small block section biopsy at about 6 months. Histologic evaluation of the region coronal to the apical edge of the calculus notch showed evidence of regeneration (new cementum, bone, and periodontal ligament). Graft particles were still present at 6 months, but no evidence of root resorption, ankylosis, or untoward inflammation was seen. This case report fulfills the proof of principle that use of ABM/P-15 can result in periodontal regeneration on previously diseased root surfaces in humans.

In vitro investigation of the potential immunomodulatory and anti-cancer activities of black pepper (Piper nigrum) and cardamom (Elettaria cardamomum).

Although the immunomodulatory effects of many herbs have been extensively studied, research related to possible immunomodulatory effects of various spices is relatively scarce. Here, the potential immunomodulatory effects of black pepper and cardamom are investigated. Our data show that black pepper and cardamom aqueous extracts significantly enhance splenocyte proliferation in a dose-dependent, synergistic fashion. Enzyme-linked immunosorbent assay experiments reveal that black pepper and cardamom significantly enhance and suppress, respectively, T helper (Th)1 cytokine release by splenocytes. Conversely, Th2 cytokine release by splenocytes is significantly suppressed and enhanced by black pepper and cardamom, respectively. Experimental evidence suggests that black pepper and cardamom extracts exert pro-inflammatory and anti-inflammatory roles, respectively. Consistently, nitric oxide production by macrophages is significantly augmented and reduced by black pepper and cardamom, respectively. Remarkably, it is evident that black pepper and cardamom extracts significantly enhance the cytotoxic activity of natural killer cells, indicating their potential anti-cancer effects. Our findings strongly suggest that black pepper and cardamom exert immunomodulatory roles and antitumor activities, and hence they manifest themselves as natural agents that can promote the maintenance of a healthy immune system. We anticipate that black pepper and cardamom constituents can be used as potential therapeutic tools to regulate inflammatory responses and prevent/attenuate carcinogenesis.

Pediatric epithelial salivary gland tumors: spectrum of histologies and cytogenetics at a children's hospital.

There are conflicting reports regarding the relative frequency of benign and malignant epithelial salivary gland tumors in children. There are only a few reports of the cytogenetic abnormalities in the pleomorphic adenomas (PA) that arise in children, and even less information regarding the pleomorphic adenoma gene 1 (PLAG1) and high motility group A2 (HMGA2 ) histochemical staining in PAs, or their correlation with histologic types (stromal vs epithelial predominance). A retrospective 14 year review of epithelial salivary gland tumors encountered at a children's hospital identified 13 tumors: 12 PAs and 1 acinic cell carcinoma (ACC). No mucoepidermoid carcinomas were identified. Tumors arose in the parotid (7) and other sites (2 submandibular, 4 minor). Ten PAs in our cohort had cytogenetic studies. Four were normal, 5 involved 8q12, and 1 involved 12q13. Immunohistochemistry identified an additional 2 PAs with PLAG1 staining, and 5 additional PAs with HMGA2 staining. One tumor with ins(18;8)(q21.1;q12q22.2) had no PLAG1 staining, but stained with HMGA2. This ins(18;8) may not have involved the PLAG1 gene. There was no demonstrable correlation of 8q12/PLAG1 staining or 12q13/HMGA2 staining with histologic type. Thus we found abnormalities in either 8q12/PLAG1 staining or 12q13/HMGA2 staining in all PAs. The HMGA2 staining in 50% of PAs suggests that it may be more frequently involved in PAs than previously thought based on cytogenetic studies, at least in children.

Nigella sativa modulates splenocyte proliferation, Th1/Th2 cytokine profile, macrophage function and NK anti-tumor activity.

AIM OF THE STUDY: Nigella sativa, also known as blackseed, has long been used in traditional medicine for treating various conditions related to the respiratory and gastrointestinal systems as well as different types of cancers. In this study, the potential immunomodulatory effects of Nigella sativa are investigated in light of splenocyte proliferation, macrophage function, and NK anti-tumor activity using BLAB/c and C57/BL6 primary cells. MATERIALS AND METHODS: Splenocyte proliferation was assessed by [(3)H]-thymidine incorporation. Griess assay was performed to evaluate NO production by macrophages. ELISA was performed to measure the level of cytokines secreted by splenocytes and macrophages. NK cytotoxic activity against YAC-1 tumor cells was examined by JAM assay. RESULTS: We demonstrate that the aqueous extract of Nigella sativa significantly enhances splenocyte proliferation in a dose-responsive manner. In addition, the aqueous extract of Nigella sativa favors the secretion of Th2, versus Th1, cytokines by splenocytes. The secretion of IL-6, TNFalpha, and NO; key pro-inflammatory mediators, by primary macrophages is significantly suppressed by the aqueous extract of Nigella sativa, indicating that Nigella sativa exerts anti-inflammatory effects in vitro. Finally, experimental evidence indicates that the aqueous extract of Nigella sativa significantly enhances NK cytotoxic activity against YAC-1 tumor cells, suggesting that the documented anti-tumor effects of Nigella sativa may be, at least in part, attributed to its ability to serve as a stimulant of NK anti-tumor activity. CONCLUSIONS: Our data present Nigella sativa as a traditionally used herb with potent immunomodulatory, anti-inflammatory, and anti-tumor effects. We anticipate that Nigella sativa ingredients may be employed as effective therapeutic agents in the regulation of diverse immune reactions implicated in various conditions and diseases such as cancer.

A comparison of fundus autofluorescence and retinal structure in patients with Stargardt disease.

PURPOSE: To improve the understanding of Stargardt disease by comparing structural changes seen on spectral domain optical coherence tomography (SD-OCT) to those visible on fundus autofluorescence (FAF). METHODS: FAF and SD-OCT were performed on 22 eyes of 11 patients with Stargardt disease. SD-OCT images were obtained at the fovea and at the eccentric preferred retinal locus (PRL). The diameters of absent (hypoautofluorescence) and abnormal FAF areas were measured. The extent of the transverse defect of the junction between the inner and outer segments of the photoreceptors (IS-OS) was measured in the foveal area. The PRL was evaluated with fundus photography and microperimetry. RESULTS: Twenty-one of 22 eyes showed defective FAF. In 17 eyes, FAF was absent in the fovea and in four eyes, FAF was abnormal. All eyes showed disorganization and/or loss of the IS-OS junction in the foveal area on SD-OCT. The diameter of the absent FAF area was smaller than the measurement of the IS-OS junction loss; the latter was closer to the diameter of the abnormal FAF area. Seventeen eyes had an eccentric PRL associated with a retinal area with no defects on FAF. CONCLUSIONS: In the majority of eyes, changes shown by SD-OCT correlated well with changes in FAF. However, in three patients, photoreceptor abnormalities were seen in the fovea on SD-OCT without an equivalent abnormality on FAF. This result suggests that in these patients, the structural integrity of the photoreceptors may be affected earlier than changes in the RPE at least as detected by FAF.

Test-retest reliability of the multifocal electroretinogram and humphrey visual fields in patients with retinitis pigmentosa.

We examined the reliability of Humphrey visual field thresholds and multifocal electroretinogram (mfERG) amplitudes and timing in a group of patients with Retinitis Pigmentosa (RP). Eight patients with RP and seven control subjects were tested five times: at baseline (visit #0), at three weekly follow-up visits (visits #1 - #3), and at three months (visit #4). For the Humphrey thresholds, differences between dB values on repeat visits were obtained. Differences between log values on repeat visits were calculated for mfERG amplitude and implicit time. We used the standard deviations of these difference scores as a measure of reliability and the means of the difference scores as a measure of progression. We found that the majority of the patients' repeat data were more variable than that of the control subjects for both the Humphrey and mfERG. We found no single factor that predicted the magnitude, or the variance, of the SD of differences scores for the patients. We recommend that each patient's reliability be assessed individually. Ultimately, the choice of an outcome measure must be guided by its reliability, as well as its ability to assess the visual function of interest.