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Sample records for clinically significant macular

  1. [Transmissing electron microscopy of the vitreo-macular border in clinically significant diabetic macular edema].

    PubMed

    Synek, S; Pác, L; Synková, M

    2007-09-01

    The authors examined samples of the epimacular tissue in clinically significant macular edema by means of the transmissing electron microscopy. They did not found morphological differences between samples from patients already treated by means of laser photocoagulation before the pars plana vitrectomy and those without the laser treatment. Findings may be divided into three groups: (1) the inner limiting membrane (ILM) covered with collagen vitreous fibers, (2) cells' elements of the fibroblasts category, and (3) fibrous astrocytes in the vitreous cortex constituting one- or multilayer cellular membranes.

  2. Monoscopic versus stereoscopic photography in screening for clinically significant macular edema.

    PubMed

    Welty, Christopher J; Agarwal, Anita; Merin, Lawrence M; Chomsky, Amy

    2006-01-01

    The purpose of the study was to determine whether monoscopic photography could serve as an accurate tool when used to screen for clinically significant macular edema. In a masked randomized fashion, two readers evaluated monoscopic and stereoscopic retinal photographs of 100 eyes. The photographs were evaluated first individually for probable clinically significant macular edema based on the Early Treatment Diabetic Retinopathy Study criteria and then as stereoscopic pairs. Graders were evaluated for sensitivity and specificity individually and in combination. Individually, reader one had a sensitivity of 0.93 and a specificity of 0.77, and reader two had a sensitivity of 0.88 and a specificity of 0.94. In combination, the readers had a sensitivity of 0.91 and a specificity of 0.86. They correlated on 0.76 of the stereoscopic readings and 0.92 of the monoscopic readings. These results indicate that the use of monoscopic retinal photography may be an accurate screening tool for clinically significant macular edema.

  3. Macular pigment Raman detector for clinical applications

    PubMed Central

    Ermakov, Igor; Ermakova, Maia; Gellermann, Werner; Bernstein, Paul S.

    2011-01-01

    Clinical studies of carotenoid macular pigments (MP) have been limited by the lack of noninvasive, objective instruments. We introduce a novel noninvasive optical instrument, an MP Raman detector, for assessment of the carotenoid status of the human retina in vivo. The instrument uses resonant excitation of carotenoid molecules in the visible wavelength range, and quantitatively measures the highly specific Raman signals that originate from the single- and double-bond stretch vibrations of the π-conjugated carotenoid molecule’s carbon backbone. The instrument is a robust, compact device and suitable for routine measurements of MP concentrations in a clinical setting. We characterized and tested the instrument in clinical studies of human subjects to validate its function and to begin to establish its role as a possible screening test for macular pathologies. We also show that the MP Raman spectroscopy technology has potential as a novel, highly specific method for rapid screening of carotenoid antioxidant levels in large populations at risk for vision loss from age-related macular degeneration, the leading cause of blindness of the elderly in the developed world. PMID:14715066

  4. The clinical utility of aflibercept for diabetic macular edema.

    PubMed

    Stewart, Michael W

    2015-01-01

    The treatment of center-involving diabetic macular edema (DME) has improved because of the proven efficacy of drugs that inhibit the effects of vascular endothelial growth factor (VEGF). The newest anti-VEGF drug, aflibercept, has recently been approved by the United States Food and Drug Administration for the treatment of center-involving DME and for diabetic retinopathy in eyes with DME. In the pivotal Phase III VISTA and VIVID trials, intravitreal aflibercept 2 mg injections every 4 or 8 weeks (after 5 monthly loading doses) produced superior gains in BCVA compared to laser/sham injections. In the Diabetic Retinopathy Clinical Research Network Protocol T trial, which featured monthly anti-VEGF monotherapy for 6 months, followed by monthly pro re nata anti-VEGF injections with laser rescue therapy from months 6 through 12, aflibercept 2 mg monthly was superior to bevacizumab 1.25 mg and ranibizumab 0.5 mg in eyes with BCVA of 20/50 or worse (aflibercept versus bevacizumab: P<0.001; aflibercept versus ranibizumab: P=0.003), but the three regimens were comparable for eyes with VA of 20/40 or better. Only in the 20/50 or worse subgroup did aflibercept achieve clinical superiority (>5 letter difference) to bevacizumab. Each treatment regimen led to significant macular thinning, with aflibercept being superior to bevacizumab in both visual acuity subgroups (P<0.001 for each), but it was not statistically superior to ranibizumab in either group. In diabetic patients, aflibercept has an excellent safety profile that does not appear to differ from laser/sham or other VEGF inhibitory drugs.

  5. Macular thickness measured by stratus optical coherence tomography in patients with diabetes type 2 and mild nonproliferative retinopathy without clinical evidence of macular edema.

    PubMed

    Pires, Isabel; Santos, Ana Rita; Nunes, Sandrina; Lobo, Conceição

    2013-01-01

    To evaluate macular thickness in eyes with mild nonproliferative diabetic retinopathy (NPDR), patients with diabetes type 2, NPDR level 20 or 35, and without evidence of clinical macular edema underwent best-corrected visual acuity assessment, color fundus photography and Stratus optical coherence tomography. Mean center point thickness (CPT) and mean central subfield (CSF) thickness were compared with those of a healthy control population. 410 eyes/patients aged 61.2 ± 8.3 years, and with glycosylated hemoglobin of 7.9 ± 1.5% were included. Mean CPT and CSF were 186.6 ± 28.4 and 215.2 ± 25 µm, respectively, significantly increased compared to healthy subjects (p < 0.001). CSF thickness was abnormally increased in 17.6% of the patients, with values within the normal range in 79.5%, and abnormally decreased in 2.9%. CPT and CSF thickness were significantly thicker in men. No systemic factors showed a significant association. A significant increase in the macular thickness was found in eyes/patients with mild NPDR without clinical macular edema; however, only 17.6% of the eyes/patients had abnormally increased values and less than 3% abnormally decreased values.

  6. Comparative Effectiveness of Three Prophylactic Strategies to Prevent Clinical Macular Edema Following Phacoemulsification Surgery

    PubMed Central

    Shorstein, Neal H.; Liu, Liyan; Waxman, Michael D.; Herrinton, Lisa J.

    2015-01-01

    PURPOSE To study the relationship of chemoprophylaxis and other factors on the occurrence of acute, clinical postoperative macular edema. DESIGN Retrospective cohort study. The drug regimens consisted of postoperative topical prednisolone acetate (PA) alone or with nonsteroidal anti-inflammatory drug (PA+NSAID) or intraoperative subconjunctival injection of 2 mg triamcinolone acetonide (TA) alone. PARTICIPANTS Patients undergoing phacoemulsification at Kaiser Permanente, Diablo Service Area, Northern California, 2007–2013. METHODS Incident macular edema diagnoses recorded 5–120 days after phacoemulsification, with visual acuity 20/40 or worse and evidence of macular thickening by optical coherence tomography were identified. Odds ratios (OR) and 95% confidence intervals (95% CI) were obtained from logistic regression analysis, conditioned on the surgeon and adjusted for year, patient age and race, diabetic retinopathy, other ocular comorbidities, systemic comorbidity and posterior capsular rupture. MAIN OUTCOME MEASURES Incident rates of acute, clinical, postoperative macular edema. RESULTS We confirmed 118 cases among 16,070 cataract surgeries (incidence, 0.73%). Compared with PA alone, the OR for the relationship of macular edema with PA+NSAID was 0.45 (95% CI, 0.21–0.95) and for TA injection was 1.21 (95% CI, 0.48–3.06). The frequency of intraocular pressure spikes ≥30 mm Hg between postoperative days 16 – 45 was 0.6% in the topical PA group, 0.3% for topical PA+NSAID (p=0.13) and 0.8% for TA (p=0.52). African-American race was associated with risk of macular edema (OR, 2.86; 95% CI, 1.41–5.79). CONCLUSIONS Adding prophylactic NSAID to PA was associated with a reduced risk of macular edema with visual acuity 20/40 or worse. Risk and safety of TA injection was similar to PA alone. Further research is needed on the prognostic significance of postoperative macular edema, the role of prophylaxis, risk in African-Americans, and the effectiveness of

  7. Clinical effects and safety of treating diabetic macular edema with intravitreal injection of ranibizumab combined with retinal photocoagulation

    PubMed Central

    Yan, Panshi; Qian, Cheng; Wang, Wenzhan; Dong, Yi; Wan, Guangming; Chen, Yue

    2016-01-01

    Background This study was designed to examine the clinical effects of treating diabetic macular edema with an intravitreal injection of ranibizumab in combination with retinal photocoagulation. Methods Sixty-two cases (75 eyes) with confirmed severe proliferative diabetic retinopathy or proliferative diabetic retinopathy in combination with macular edema were randomly divided into the observation group (37 eyes were given an intravitreal injection of ranibizumab combined with retinal photocoagulation) and the control group (38 eyes received retinal photocoagulation only). Vision, fundus condition, central macular thickness, and the macular leakage area were recorded before and after treatment. Results The best-corrected visual acuity and macular leakage area were similar between the observation and control groups (P>0.05). The best-corrected visual acuity in the observation group was higher than that in the control group 3 and 6 months after treatment (P<0.05) and showed a rising tendency. The macular leakage area in the observation group was significantly lower than that in the control group 1 and 3 months after treatment (P<0.05). However, the macular leakage area was similar 6 months after treatment (P>0.05). The central macular thickness of the observation group was lower than that in the control group 1, 3, and 6 months after treatment (P<0.05). The laser energy used in the observation group was also smaller than that in the control group (P<0.05). The intraocular pressure was not significantly different between the groups (P<0.05). No patients in the two groups developed eye or systemic complications, such as glaucoma, cataract, or vitreous hemorrhage during treatment. Conclusion Intravitreal injection of ranibizumab combined with retinal photocoagulation was proven to be effective in treating diabetic macular edema as it improved vision and resulted in fewer complications. PMID:27103811

  8. [Macular serpiginous choroiditis complicated by macular hole].

    PubMed

    Brănişteanu, D; Moraru, Andreea

    2014-01-01

    Macular serpiginouschoroiditis is a rare variant of serpiginous choroiditis characterized by a severe recurrent inflammation of both central choroid and retinal pigment epithelium. Visual prognosis is severe due to subsequent distruction of retinal structures. Permanent central visual loss is the consequence of retinal pigment epithelium hyper or hypoplasia and/or subretinal neovascularization leading to fibrous scarring. This article reports the unusual case of rapid development of a macular hole soon after the onset of characteristic clinical features. Despite anti-inflammatory treatment and successful macular hole surgery the visual function remained significantly impaired by secondary central retinal pigment epithelium changes.

  9. Light and macular degeneration: a biophysical and clinical perspective.

    PubMed

    Mainster, M A

    1987-01-01

    The evidence linking photic retinopathy to ageing macular degeneration (AMD) is compelling but circumstantial. The biophysical foundations of ageing theory are presented, in addition to an analysis of retinal senescence and the potential contributory role of photochemical retinal damage. Although there is pressure to implement clinical therapy for AMD based on laboratory studies of photic retinopathy, there is no evidence at this time that any such therapy is effective. Nonetheless, until the relationship between photic retinopathy and AMD is better understood, it is appropriate for individuals to use ultraviolet and deep blue protective sunglasses in bright environments, particularly if they have reduced ocular pigmentation or if they are aphakes or pseudophakes without an ultraviolet-protective intraocular lens.

  10. Wet Macular Degeneration

    MedlinePlus

    Wet macular degeneration Overview By Mayo Clinic Staff Wet macular degeneration is a chronic eye disease that causes blurred vision ... of the retina responsible for central vision. Wet macular degeneration is one of two types of age-related ...

  11. Dry Macular Degeneration

    MedlinePlus

    Dry macular degeneration Overview By Mayo Clinic Staff Dry macular degeneration is a common eye disorder among people over 65. ... vision in your direct line of sight. Dry macular degeneration may first develop in one eye and then ...

  12. Clinical Investigation of the Posterior scleral contraction to Treat Macular Traction Maculopathy in Highly Myopic Eyes

    PubMed Central

    Pan, An-Peng; Wan, Ting; Zhu, Shuang-Qian; Dong, Liang; Xue, An-Quan

    2017-01-01

    Myopic traction maculopathy (MTM) can cause vision disabilities in highly myopic eyes. This retrospective case series investigated the clinical outcomes of posterior scleral contraction (PSC) using genipin-cross-linked sclera as the material to treat MTM in highly myopic eyes. In total, 32 eyes from 29 highly myopic patients who underwent PSC for MTM were recruited. The changes in best-corrected visual acuity (BCVA) and axial length were evaluated, macular reattachment and macular hole (MH) closure was assessed by optical coherence tomography, and complications were evaluated. At the final follow-up, the retina was completely reattached in 25 eyes (78.1%), essentially reattached in 4 eyes (12.5%), and partially reattached in 3 eyes (9.4%). The logMAR BCVA improved significantly from 1.18 ± 0.45 preoperatively to 0.87 ± 0.45 postoperatively (P < 0.001). The 32 eyes were further divided into the MH group (16 eyes) and the non-MH group (16 eyes) for comparison. The MH was closed in 9 eyes (56.3%). The retinal reattachment rate was 75.0% in the MH group and 81.25% in the non-MH group, and the logMAR BCVA improved significantly in both groups. The PSC using genipin-cross-linked sclera as the material can effectively treat MTM in highly myopic eyes, and significant visual improvement can be achieved with minimal complications. PMID:28220890

  13. Intravitreal diclofenac versus intravitreal bevacizumab in naive diabetic macular edema: a randomized double-masked clinical trial.

    PubMed

    Soheilian, Masoud; Karimi, Saeed; Ramezani, Alireza; Montahai, Talieh; Yaseri, Mehdi; Soheilian, Roham; Peyman, Gholam A

    2015-06-01

    The purpose of the study is to compare single injection of intravitreal diclofenac (IVD) with intravitreal bevacizumab (IVB) in the treatment of eyes with naïve diabetic macular edema (DME). In this randomized clinical trial, 57 eyes of 57 patients were randomly assigned to IVD group (30 eyes), cases who received a single intravitreal injection of diclofenac (500 μg/0.1 ml), and IVB group (27 eyes), cases who received a single intravitreal injection of bevacizumab (1.25 mg). Change in best-corrected visual acuity in logMAR at week 12 was the primary outcome measure. Secondary outcomes included changes in central macular thickness, macular leakage, and potential injection-related complications. Best-corrected visual acuity improved significantly more in the IVD group than in the IVB group (P = 0.033), from 0.57 ± 0.25 to 0.49 ± 0.31 versus 0.55 ± 0.24-0.59 ± 0.27 logMAR at 12 weeks, respectively. However, the difference of macular thickness changes was in favor of IVB, but not to a significant level. The amount of change in leakage was not significantly different between the groups either. None of the eyes, in either group, developed ocular hypertension (≥23 mmHg) or cataract progression. No important injection-related complication was observed during the study period. This study demonstrated the superiority of IVD over IVB in the treatment of naïve DME regarding functional, but not anatomical outcomes. Therefore, using IVD as an adjunct or even alternative to other treatments might enhance the functional outcomes in such cases. Further studies are warranted to confirm potential benefit of IVD observed in this study.

  14. Clinical evidence of intravitreal triamcinolone acetonide in the management of age-related macular degeneration.

    PubMed

    Becerra, E M; Morescalchi, F; Gandolfo, F; Danzi, P; Nascimbeni, G; Arcidiacono, B; Semeraro, F

    2011-02-01

    of cataract. Nevertheless, cataract surgery may stimulate the development of CNV (result in stimulating CNV). However, in large, randomized, clinical trials on combination therapy of TA and PDT, visual acuity failed to show an improvement, even though the lesion size and subretinal fluid had decreased, compared to controls treated with PDT alone. Some authors reported an increased risk of developing macular atrophy after the combination therapy with IVTA and PDT. Reduction of the PDT fluence rate in association with the use of steroids resulted in reducing the risk of macular atrophy and in a better visual acuity outcome. The introduction of anti-VEGF-based drugs has revolutionized the treatment of AMD and has replaced all the previous therapies used for CNV. Visual improvement becomes an expectation in a higher proportion of patients, previously limited to minimizing vision loss. Anti-VEGF therapy also resulted in superior visual improvement compared to all types of combination therapy with IVT and PDT. Nevertheless, anti-VEGF monotherapy also has many limitations due to the need of repetitive treatments, increased costs and tachyphylaxis. Treatment regimens involving TA in combination therapy with anti-VEGF and PDT may preserve benefits for substantially longer periods. A question remains open on whether a combination treatment with anti-VEGF, triamcinolone and/or PDT may be a treatment option in patients with exudative AMD, by offering, with one cycle of therapy, functional VA benefits comparable to those observed with continued monthly anti-VEGF therapy. Further trials, of higher scientific significance, are needed to study the potential of these treatment options.

  15. Prognostic implications of imaging in atrophic macular degeneration and its use in clinical practice and clinical trial design.

    PubMed

    Lim, Paul Cc; Layton, Christopher J

    2016-07-01

    Clinical prognostic markers in atrophic age-related macular degeneration include the extent of existing atrophy, fundus autofluorescence (FAF) patterns and optical coherence tomography changes in the outer retina/retinal pigment epithelium interface. The prognostic implications of these findings may be used to determine not just the rate of disease progression but also influence the likelihood, magnitude and clinical relevance of therapy responses. FAF phenotypes have been extensively investigated; however, the pathophysiological mechanisms behind their appearance have not been fully elucidated. Optical coherence tomography imaging is additive to FAF imaging in atrophic age-related macular degeneration, allowing the visualization of detail not available through FAF imaging whilst also displaying subtle changes correlating with the FAF phenotypes themselves, thereby giving clues to their histological determinates. The developing understanding of these imaging modalities and consequent development of prognostically useful classification systems have widespread implication in clinical care and clinical trial design.

  16. Bevacizumab for neovascular age-related macular degeneration in Chinese patients in a clinical setting

    PubMed Central

    Ng, Danny Siu-Chun; Kwok, Alvin Kwan-Ho; Tong, Justin Man-Kit; Chan, Clement Wai-Nang; Li, Walton Wai-Tat

    2016-01-01

    AIM To determine the outcome of non-investigational treatment with intravitreal bevacizumab (IVB) in neovascular age-related macular degeneration (AMD) patients. METHODS Retrospective chart review of 81 eyes with neovascular AMD followed-up for at least 12mo and received 3-monthly loading IVB injections. Re-treat was based upon the individual clinician's judgment. Best-corrected visual acuity (BCVA) and optical coherence tomography measurements of central foveal thickness outcomes were evaluated at 12, 24mo. RESULTS Eighty-one eyes (of 75 patients) completed 12mo of follow-up and 44 eyes (of 41 patients) completed 24mo of follow-up. The mean baseline logMAR BCVA significantly improved from 0.94±0.69 to 0.85±0.68 at 12mo (P<0.001) and from 0.91±0.65 to 0.85±0.60 (P=0.004) at 24mo. The proportion of eyes that lost <15 logMAR letters at 12mo was 90.1% and at 24mo was 81.8%. IVB was effective in improving visual acuity in both treatment naïve and previous photodynamic therapy (PDT)-treated subgroups. Treatment naive patients required significantly fewer injections than patients with prior PDT. Multiple regression analysis identified that poorer baseline visual acuity was associated with greater improvement in visual acuity (P=0.015). CONCLUSION Fewer injections in clinical practice may result in suboptimal visual outcomes compared with clinical trials of IVB in neovascular AMD patients. Poor baseline visual acuity and prior PDT treatment may also improve vision after IVB. The safety and durability of effect was maintained at 24mo. PMID:27158614

  17. [Hypertriglyceridemia: concept and clinical significance].

    PubMed

    Hirano, Tsutomu

    2013-09-01

    Hypertriglyceridemia is a common lipid disorder as well as hypercholesterolemia. However clinical significance of hypertriglyceridemia is not fully understood because of its heterogeneous lipoprotein phenotypes and complex etiology. Severe hypertriglyceridemia increases the risk for pancreatitis, whereas mild or moderate hypertriglyceridemia may be a risk factor for cardiovascular disease. Patients with hypertriglyceridemia are usually accompanied by other cardiovascular related disorders, such as central obesity, type 2 diabetes, and liver steatosis. Ectopic fat accumulation is often seen in hypertriglyceridemic subjects and various organ injuries are developed by the lipotoxicity. Hypertriglyceridemia is strongly associated with remnant lipoprotein accumulation, increased small dense LDL, and low HDL-cholesterol. All these lipid abnormalities are recognized as cardiovascular risk factors. The pathophysiology of lipoprotein metabolism related to the hypertriglyceridemia is summarized in this brief review.

  18. Prognostic significance of foveal capillary drop-out and previous panretinal photocoagulation for diabetic macular oedema treated with ranibizumab

    PubMed Central

    Ebneter, Andreas; Wolf, Sebastian; Zinkernagel, Martin S

    2016-01-01

    Aims To investigate the prognostic significance of macular capillary drop-out and previous panretinal laser photocoagulation in diabetic macular oedema treated with intravitreal ranibizumab. Methods Retrospective observational case series. Treatment-naive patients with diabetic macular oedema that had been treated with intravitreal ranibizumab as per the RESTORE study protocol for at least 12 months were included. Some patients (n=15) had previous panretinal laser photocoagulation. Best-corrected visual acuity and central retina thickness were recorded monthly. The foveal avascular zone and the perifoveal capillaries were quantitatively and qualitatively assessed on fluorescein angiography on two occasions during the observational period. Results From the 46 eyes (46 patients) in this study, 13 (28%) had evidence of perifoveal capillary drop-out. Central retinal thickness was significantly thinner at baseline (p=0.02) and throughout the study period in these eyes compared with those with normal perifoveal capillaries. Both groups responded with a significant gain of best-corrected visual acuity to ranibizumab treatment (7.6±3.3 and 6.3±1.3 ETDRS letters, respectively). Eyes with previous panretinal laser photocoagulation displayed a comparable final outcome regarding function and morphology, requiring a similar intensity of intravitreal injections. Conclusions Perifoveal capillary drop-out did not limit the gain of visual acuity from intravitreal ranibizumab treatment. The reduction of central retina thickness was similar to that seen in eyes with normal perifoveal capillaries. Central retinal thickness in eyes with perifoveal capillary drop-out was generally reduced. However, this did not affect their benefit from treatment. Ranibizumab did not increase the amount of perifoveal capillary loss. PMID:26187951

  19. Macular telangiectasia type 2

    PubMed Central

    Issa, Peter Charbel; Gillies, Mark C.; Chew, Emily Y.; Bird, Alan C.; Heeren, Tjebo F.C.; Peto, Tunde; Holz, Frank G.; Scholl, Hendrik P.N.

    2013-01-01

    Macular telangiectasia type 2 is a bilateral disease of unknown cause with characteristic alterations of the macular capillary network and neurosensory atrophy. Its prevalence may be underestimated and has recently been shown to be as high as 0.1% in persons 40 years and older. Biomicroscopy may show reduced retinal transparency, crystalline deposits, mildly ectatic capillaries, blunted venules, retinal pigment plaques, foveal atrophy, and neovascular complexes. Fluorescein angiography shows telangiectatic capillaries predominantly temporal to the foveola in the early phase and a diffuse hyperfluorescence in the late phase. High-resolution optical coherence tomography (OCT) may reveal disruption of the photoreceptor inner segment–outer segment border, hyporeflective cavities at the level of the inner or outer retina, and atrophy of the retina in later stages. Macular telangiectasia type 2 shows a unique depletion of the macular pigment in the central retina and recent therapeutic trials showed that such depleted areas cannot re-accumulate lutein and zeaxanthin after oral supplementation. There have been various therapeutic approaches with limited or no efficacy. Recent clinical trials with compounds that block vascular endothelial growth factor (VEGF) have established the role of VEGF in the pathophysiology of the disease, but have not shown significant efficacy, at least for the nonneovascular disease stages. Recent progress in structure–function correlation may help to develop surrogate outcome measures for future clinical trials. In this review article, we summarize the current knowledge on macular telangiectasia type 2, including the epidemiology, the genetics, the clinical findings, the staging and the differential diagnosis of the disease. Findings using retinal imaging are discussed, including fluorescein angiography, OCT, adaptive optics imaging, confocal scanning laser ophthalmoscopy, and fundus autofluorescence, as are the findings using visual

  20. Dry age-related macular degeneration: A currently unmet clinical need.

    PubMed

    Girmens, Jean-François; Sahel, José-Alain; Marazova, Katia

    2012-08-01

    Age-related macular degeneration (AMD) is a leading cause of severe visual impairment and disability in older people worldwide. Although considerable advances in the management of the neovascular form of AMD have been made in the last decade, no therapy is yet available for the advanced dry form of AMD (geographic atrophy). This review focuses on current trends in the development of new therapies targeting specific pathophysiological pathways of dry AMD. Increased understanding of the complex mechanisms that underlie dry AMD will help to address this largely unmet clinical need.

  1. Dry age-related macular degeneration: A currently unmet clinical need

    PubMed Central

    Girmens, Jean-François; Sahel, José-Alain; Marazova, Katia

    2012-01-01

    Summary Age-related macular degeneration (AMD) is a leading cause of severe visual impairment and disability in older people worldwide. Although considerable advances in the management of the neovascular form of AMD have been made in the last decade, no therapy is yet available for the advanced dry form of AMD (geographic atrophy). This review focuses on current trends in the development of new therapies targeting specific pathophysiological pathways of dry AMD. Increased understanding of the complex mechanisms that underlie dry AMD will help to address this largely unmet clinical need. PMID:25343081

  2. Macular Ganglion Cell -Inner Plexiform Layer Thickness Is Associated with Clinical Progression in Mild Cognitive Impairment and Alzheimers Disease

    PubMed Central

    Choi, Seong Hye; Park, Sang Jun

    2016-01-01

    Purpose We investigated the association of the macular ganglion cell-inner plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (RNFL) thicknesses with disease progression in mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Methods We recruited 42 patients with AD, 26 with MCI, and 66 normal elderly controls. The thicknesses of the RNFL and GCIPL were measured via spectral-domain optic coherent tomography in all participants at baseline. The patients with MCI or AD underwent clinical and neuropsychological tests at baseline and once every year thereafter for 2 years. Results The Clinical Dementia Rating scale-Sum of Boxes (CDR-SB) score exhibited significant negative relationships with the average GCIPL thickness (β = -0.15, p < 0.05) and the GCIPL thickness in the superotemporal, superonasal, and inferonasal sectors. The composite memory score exhibited significant positive associations with the average GCIPL thickness and the GCIPL thickness in the superotemporal, inferonasal, and inferotemporal sectors. The temporal RNFL thickness, the average and minimum GCIPL thicknesses, and the GCIPL thickness in the inferonasal, inferior, and inferotemporal sectors at baseline were significantly reduced in MCI patients who were converted to AD compared to stable MCI patients. The change of CDR-SB from baseline to 2 years exhibited significant negative associations with the average (β = -0.150, p = 0.006) and minimum GCIPL thicknesses as well as GCIPL thickness in the superotemporal, superior, superonasal, and inferonasal sectors at baseline. Conclusions Our data suggest that macular GCIPL thickness represents a promising biomarker for monitoring the progression of MCI and AD. PMID:27598262

  3. Macular Preprocessing of Linear Acceleratory Stimuli: Implications for the Clinic

    NASA Technical Reports Server (NTRS)

    Ross, M. D.; Hargens, Alan R. (Technical Monitor)

    1996-01-01

    Three-dimensional reconstructions of innervation patterns in rat maculae were carried out using serial section images sent to a Silicon Graphics workstation from a transmission electron microscope. Contours were extracted from mosaicked sections, then registered and visualized using Biocomputation Center software. Purposes were to determine innervation patterns of type II cells and areas encompassed by vestibular afferent receptive fields. Terminals on type II cells typically are elongated and compartmentalized into parts varying in vesicular content; reciprocal and serial synapses are common. The terminals originate as processes of nearby calyces or from nerve fibers passing to calyces outside the immediate vicinity. Thus, receptive fields of the afferents overlap in unique ways. Multiple processes are frequent; from 4 to 6 afferents supply 12-16 terminals on a type II cell. Processes commonly communicate with two type II cells. The morphology indicates that extensive preprocessing of linear acceleratory stimuli occurs peripherally, as is true also of visual and olfactory systems. Clinically, this means that loss of individual nerve fibers may not be noticed behaviorally, due to redundancy (receptive field overlap). However, peripheral processing implies the presence of neuroactive agents whose loss can acutely or chronically alter normal peripheral function and cause balance disorders. (Platform presentation preferred - Theme 11)

  4. Clinical and genetic characterization of a Danish family with North Carolina macular dystrophy

    PubMed Central

    Rosenberg, Thomas; Roos, Ben; Johnsen, Thorkild; Bech, Niels; Scheetz, Todd E.; Larsen, Michael; Stone, Edwin M.

    2010-01-01

    Purpose To describe the phenotype of a family with an autosomal dominant macular dystrophy and identify the chromosomal location of the gene that causes this phenotype. Methods Twelve members of a three-generation family underwent routine clinical examination, including fundus photography. Four of the patients underwent extended examination with Goldmann perimetry, full-field electroretinogram, dark adaptation, and color vision testing, and two patients underwent optical coherence tomography and fundus autofluorescence examination. DNA samples were obtained from 12 family members and 3 spouses and genotyped at the known North Carolina Macular Dystrophy (NCMD) locus on chromosome 6q (MCDR1: OMIM 136550) using short tandem repeat polymorphisms. DNA samples were subsequently examined with a genome-wide scan of single nucleotide polymorphisms and the genotypes that were produced were studied with linkage and haplotype analyses. Results The 10 affected family members had clinical findings of macular lesions that are typical for NCMD. The small drusen-like yellowish lesions of mild NCMD were hyperautofluorescent. Hyperpigmented foveal lesions were surrounded by a zone of confluent hyperautofluorescence. Linkage analysis of short tandem repeat polymorphism genetic markers excluded the NCMD locus on chromosome 6. However, analysis of single nucleotide polymorphism genotypes from a genome-wide scan showed that NCMD in our pedigree is linked to a region on chromosome 5p that overlaps the previously mapped macular dystrophy (MCDR3) locus with a maximum log of the odds (LOD) score of 2.69 at a recombination fraction of 0.00 (markers D5S406, D5S1987, and D5S2505). Discussion We report the first pedigree with NCMD from Scandinavia, and the first confirmation that a gene for this condition is located on chromosome 5p13-p15. The bright elements or lesions typical of NCMD differed from drusen in that no sign of accumulation of material between the retinal pigment epithelium and

  5. Macular pigmentation of uncertain aetiology revisited: two case reports and a proposed algorithm for clinical classification.

    PubMed

    Chandran, Veena; Kumarasinghe, Sujith Prasad

    2017-02-01

    Ashy dermatosis, erythema dyschromicum perstans, lichen planus pigmentosus and idiopathic eruptive macular pigmentation are various types of acquired macular hyperpigmentation disorders of the skin described in literature. However, a global consensus on the definitions of these entities is lacking. We report two cases of acquired macular (hyper)pigmentation of uncertain aetiology diagnosed as ashy dermatosis and attempt to clarify the various confusing nosologies based on existing literature. We infer that acquired small and large macular pigmentation of uncertain aetiology should be considered separate from that associated with lichen planus. We also propose a diagnostic algorithm for patients with acquired macular hyperpigmentation.

  6. Improving Function in Age-Related Macular Degeneration: A Randomized Clinical Trial

    PubMed Central

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Massof, Robert W.; Leiby, Benjamin E.; Ho, Allen C.; Tasman, William S.

    2013-01-01

    Purpose To compare the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) to improve Targeted Vision Function in Age-Related Macular Degeneration (AMD). Design Single-masked, attention controlled randomized clinical trial with outcome assessments at 3 months (main trial endpoint) and 6 months (maintenance effects). Participants Patients with AMD (N = 241) attending retina practices. Interventions PST uses a structured problem-solving approach to reduce vision-related task difficulty. ST is a standardized attention control treatment. Main Outcome Measures Targeted Vision Function (TVF); National Eye Institute Vision Function Questionnaire - 25 plus Supplement (NEI VFQ); Activities Inventory (AI); and Vision-Related Quality of Life. Results There were no significant between-group differences in TVF scores at 3 months (p = 0.47) or 6 months (p = 0.62). For PST subjects, mean [standard deviation (SD)] TVF scores improved from 2.71 (0.52) at baseline to 2.18 (0.88) at 3 months (p = 0.001) and were 2.18 (0.95) at 6 months (change from 3 to 6 months, p = .74). For ST subjects, TVF scores improved from 2.73 (0.52) at baseline to 2.14 (0.96) at 3 months (p = 0.001) and were 2.15 (0.96) at 6 months (change from 3 to 6 months, p = .85). Similar proportions of PST and ST subjects had less difficulty performing a TVF goal at 3 months (77.4% vs. 78.6%, respectively; p = 0.83) and 6 months (76.2% vs. 79.1%, respectively; p = 0.61). There were no significant changes in the NEI VFQ or AI. Vision-related quality-of-life improved for PST relative to ST subjects at 3 months [F (4,192) = 2.46; p = 0.05] and 6 months [F (4,178) = 2.55; p = 0.05)]. PST subjects also developed more adaptive coping strategies than ST subjects. Conclusions We found that PST was not superior to ST at improving vision function in patients with AMD but PST improved their vision-related quality of life. Despite the benefits of anti-vascular endothelial growth factor (anti-VEGF) treatments

  7. Neovascular age-related macular degeneration without drusen in the fellow eye: clinical spectrum and therapeutic outcome

    PubMed Central

    Chung, Wing H; van Dijk, Elon H C; Mohabati, Danial; Dijkman, Greet; Yzer, Suzanne; de Jong, Eiko K; Fauser, Sascha; Schlingemann, Reinier O; Hoyng, Carel B; Boon, Camiel J F

    2017-01-01

    Purpose To investigate the clinical characteristics and therapeutic outcome of patients with neovascular age-related macular degeneration (nAMD) in 1 eye, without drusen in the fellow eye. Patients and methods Medical records of 381 patients were analyzed to identify the cases. The main outcomes included Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) and change in central retinal thickness (CRT). These parameters were reviewed at baseline, first follow-up visit, and after 6, 12, and 24 months. Results Out of 381 patients, 29 cases (8%) were included (of whom 3 had polypoidal choroidal vasculopathy [PCV]) who were treated with anti-vascular endothelial growth factor (anti-VEGF) therapy which was supplemented by photodynamic therapy (PDT) in the PCV patients. Overall, no statistically significant change in mean BCVA was observed during follow-up. BCVA improved or remained stable (defined as a gain in BCVA, a stable BCVA, or a loss of <5 ETDRS letters) in 22 patients (76%), and 7 patients (23%) had lost ≥5 ETDRS letters at final follow-up. A gain of ≥15 ETDRS letters at final follow-up was seen in 5 patients (17%). Mean CRT had decreased significantly with 99 µm (P<0.001) at 24 months after the initial visit. Conclusion There is a clinical spectrum of nAMD that is not associated with drusen in the fellow eye. Patients with nAMD without drusen in the fellow eye respond to anti-VEGF treatment and, in cases of PCV, to supplemental PDT. The pathophysiology of this spectrum of nAMD may be different from drusen-associated age-related macular degeneration. PMID:28053502

  8. Significant results: statistical or clinical?

    PubMed Central

    2016-01-01

    The null hypothesis significance test method is popular in biological and medical research. Many researchers have used this method for their research without exact knowledge, though it has both merits and shortcomings. Readers will know its shortcomings, as well as several complementary or alternative methods, as such the estimated effect size and the confidence interval. PMID:27066201

  9. The rs2071559 AA VEGFR-2 genotype frequency is significantly lower in neovascular age-related macular degeneration patients.

    PubMed

    Lazzeri, Stefano; Orlandi, Paola; Figus, Michele; Fioravanti, Anna; Cascio, Elisa; Di Desidero, Teresa; Agosta, Elisa; Canu, Bastianina; Sartini, Maria Sole; Danesi, Romano; Nardi, Marco; Bocci, Guido

    2012-01-01

    In this prospective, case-control genetic study, 120 consecutive neovascular age-related macular degeneration (AMD) cases and 78 controls were enrolled. Two SNPs (rs2071559 and rs1870377) of VEGF-A receptor-2 (VEGFR-2) gene were analyzed with the technique of Real-Time PCR to investigate a genetic link between AMD and VEGFR-2 gene polymorphisms in Italian patients. The frequency of the VEGFR-2 genotype rs2071559 AA was significantly lower (18.33%) in patients with AMD than in the control subjects (34.62%; P = 0.0095, chi-square test; P(corr) = 0.038; OR = 0.42, 95% CI 0.22 to 0.82). In conclusion, although with the limitations of a small sample size and the few SNPs studied, this study demonstrates a lower frequency of VEGFR-2 rs2071559 AA genotype in an AMD patient population, suggesting future studies on the role VEGFR-2 SNPs.

  10. The rs2071559 AA VEGFR-2 Genotype Frequency Is Significantly Lower in Neovascular Age-Related Macular Degeneration Patients

    PubMed Central

    Lazzeri, Stefano; Orlandi, Paola; Figus, Michele; Fioravanti, Anna; Cascio, Elisa; Di Desidero, Teresa; Agosta, Elisa; Canu, Bastianina; Sartini, Maria Sole; Danesi, Romano; Nardi, Marco; Bocci, Guido

    2012-01-01

    In this prospective, case-control genetic study, 120 consecutive neovascular age-related macular degeneration (AMD) cases and 78 controls were enrolled. Two SNPs (rs2071559 and rs1870377) of VEGF-A receptor-2 (VEGFR-2) gene were analyzed with the technique of Real-Time PCR to investigate a genetic link between AMD and VEGFR-2 gene polymorphisms in Italian patients. The frequency of the VEGFR-2 genotype rs2071559 AA was significantly lower (18.33%) in patients with AMD than in the control subjects (34.62%; P = 0.0095, chi-square test; Pcorr = 0.038; OR = 0.42, 95% CI 0.22 to 0.82). In conclusion, although with the limitations of a small sample size and the few SNPs studied, this study demonstrates a lower frequency of VEGFR-2 rs2071559 AA genotype in an AMD patient population, suggesting future studies on the role VEGFR-2 SNPs. PMID:22919317

  11. Differentiating full thickness macular holes from impending macular holes and macular pseudoholes

    PubMed Central

    Tsujikawa, M.; Ohji, M.; Fujikado, T.; Saito, Y.; Motokura, M.; Ishimoto, I.; Tano, Y.

    1997-01-01

    AIMS—The reliability of scanning laser ophthalmoscope (SLO) microperimetry in differentiating full thickness macular holes from macular pseudoholes and impending macular holes was evaluated.
METHODS—106 eyes with the clinical diagnosis of full thickness macular holes, macular pseudoholes, and impending (stage 1) macular holes were examined for the presence of deep or relative scotoma using SLO microperimetry. The relation between these scotomas and the clinical diagnosis was studied.
RESULTS—Deep and relative scotomas were detected in all 57 eyes with clinically defined full thickness macular holes. In contrast, among 49 eyes diagnosed with macular pseudoholes or impending macular holes, no deep and only one relative scotoma was observed. The sensitivity of the presence of a deep scotoma as an indicator of the clinical diagnosis of a full thickness macular hole was 100% (57 of 57), and the specificity was 100% (49 of 49). The sensitivity of the presence of a relative scotoma was 100% (57 of 57) and the specificity was 98.0% (48 of 49).
CONCLUSION—With SLO microperimetry, full thickness macular holes can be precisely and objectively distinguished from other conditions that mimic macular holes.

 PMID:9059244

  12. Age-related macular degeneration-clinical review and genetics update.

    PubMed

    Ratnapriya, R; Chew, E Y

    2013-08-01

    Age-related macular degeneration (AMD) is the leading cause of central vision impairment in persons over the age of 50 years in developed countries. Both genetic and non-genetic (environmental) factors play major roles in AMD etiology, and multiple gene variants and lifestyle factors such as smoking have been associated with the disease. While dissecting the basic etiology of the disease remains a major challenge, current genetic knowledge has provided opportunities for improved risk assessment, molecular diagnosis and clinical testing of genetic variants in AMD treatment and management. This review addresses the potential of translating the wealth of genetic findings for improved risk prediction and therapeutic intervention in AMD patients. Finally, we discuss the recent advancement in genetics and genomics and the future prospective of personalized medicine in AMD patients.

  13. Prospects for clinical use of reprogrammed cells for autologous treatment of macular degeneration.

    PubMed

    Alvarez Palomo, Ana Belen; McLenachan, Samuel; Chen, Fred K; Da Cruz, Lyndon; Dilley, Rodney J; Requena, Jordi; Lucas, Michaela; Lucas, Andrew; Drukker, Micha; Edel, Michael J

    2015-01-01

    Since the discovery of induced pluripotent stem cells (iPSC) in 2006, the symptoms of many human diseases have been reversed in animal models with iPSC therapy, setting the stage for future clinical development. From the animal data it is clear that iPSC are rapidly becoming the lead cell type for cell replacement therapy and for the newly developing field of iPSC-derived body organ transplantation. The first human pathology that might be treated in the near future with iPSC is age-related macular degeneration (AMD), which has recently passed the criteria set down by regulators for phase I clinical trials with allogeneic human embryonic stem cell-derived cell transplantation in humans. Given that iPSC are currently in clinical trial in Japan (RIKEN) to treat AMD, the establishment of a set of international criteria to make clinical-grade iPSC and their differentiated progeny is the next step in order to prepare for future autologous cell therapy clinical trials. Armed with clinical-grade iPSC, we can then specifically test for their threat of cancer, for proper and efficient differentiation to the correct cell type to treat human disease and then to determine their immunogenicity. Such a rigorous approach sets a far more relevant paradigm for their intended future use than non-clinical-grade iPSC. This review focuses on the latest developments regarding the first possible use of iPSC-derived retinal pigment epithelial cells in treating human disease, covers data gathered on animal models to date and methods to make clinical-grade iPSC, suggests techniques to ensure quality control and discusses possible clinical immune responses.

  14. Clinical and genetic factors associated with progression of geographic atrophy lesions in age-related macular degeneration.

    PubMed

    Grassmann, Felix; Fleckenstein, Monika; Chew, Emily Y; Strunz, Tobias; Schmitz-Valckenberg, Steffen; Göbel, Arno P; Klein, Michael L; Ratnapriya, Rinki; Swaroop, Anand; Holz, Frank G; Weber, Bernhard H F

    2015-01-01

    Worldwide, age-related macular degeneration (AMD) is a serious threat to vision loss in individuals over 50 years of age with a pooled prevalence of approximately 9%. For 2020, the number of people afflicted with this condition is estimated to reach 200 million. While AMD lesions presenting as geographic atrophy (GA) show high inter-individual variability, only little is known about prognostic factors. Here, we aimed to elucidate the contribution of clinical, demographic and genetic factors on GA progression. Analyzing the currently largest dataset on GA lesion growth (N = 388), our findings suggest a significant and independent contribution of three factors on GA lesion growth including at least two genetic factors (ARMS2_rs10490924 [P < 0.00088] and C3_rs2230199 [P < 0.00015]) as well as one clinical component (presence of GA in the fellow eye [P < 0.00023]). These correlations jointly explain up to 7.2% of the observed inter-individual variance in GA lesion progression and should be considered in strategy planning of interventional clinical trials aimed at evaluating novel treatment options in advanced GA due to AMD.

  15. Update on Clinical Trials in Dry Age-related Macular Degeneration.

    PubMed

    Taskintuna, Ibrahim; Elsayed, M E A Abdalla; Schatz, Patrik

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future.

  16. Update on Clinical Trials in Dry Age-related Macular Degeneration

    PubMed Central

    Taskintuna, Ibrahim; Elsayed, M. E. A. Abdalla; Schatz, Patrik

    2016-01-01

    This review article summarizes the most recent clinical trials for dry age-related macular degeneration (AMD), the most common cause of vision loss in the elderly in developed countries. A literature search through websites https://www.pubmed.org and https://www.clinicaltrials.gov/, both accessed no later than November 04, 2015, was performed. We identified three Phase III clinical trials that were completed over the recent 5 years Age-Related Eye Disease Study 2 (AREDS2), implantable miniature telescope and tandospirone, and several other trials targeting a variety of mechanisms including, oxidative stress, complement inhibition, visual cycle inhibition, retinal and choroidal blood flow, stem cells, gene therapy, and visual rehabilitation. To date, none of the biologically oriented therapies have resulted in improved vision. Vision improvement was reported with an implantable mini telescope. Stem cells therapy holds a potential for vision improvement. The AREDS2 formulas did not add any further reduced risk of progression to advanced AMD, compared to the original AREDS formula. Several recently discovered pathogenetic mechanisms in dry AMD have enabled development of new treatment strategies, and several of these have been tested in recent clinical trials and are currently being tested in ongoing trials. The rapid development and understanding of pathogenesis holds promise for the future. PMID:26957835

  17. Quantitative assessment of macular thickness in normal subjects and patients with diabetic retinopathy by scanning retinal thickness analyser

    PubMed Central

    Oshima, Y.; Emi, K.; Yamanishi, S.; Motokura, M.

    1999-01-01

    AIMS—To evaluate the scanning retinal thickness analyser (RTA), a novel non-invasive imaging instrument, in diagnosing and quantitatively characterising diabetic macular oedema, and to investigate the relation between central macula thickness measured by RTA and other clinical examinations.
METHODS—Central macular thickness was measured using the RTA in 40 normal subjects and 60 patients with diabetic retinopathy. The reproducibility of the retinal thickness measurements was evaluated by calculating the mean of the inter- and intrasession variations. Central macular thickness was correlated with the results of visual acuity measurements, biomicroscopy, and fluorescein angiography.
RESULTS—Intra- and intersession reproducibility of the RTA in normal subjects was plus or minus 5.2% (16 µm) and plus or minus 6.1% (19 µm), respectively. The mean central macular thickness was 182 (SD 16) µm in normal subjects, 283 (116) µm in diabetic eyes without clinically significant macular oedema (CSMO), and 564 (168) µm in diabetic eyes with CSMO. Central macular thickness was significantly greater (p<0.001) in eyes with diabetic retinopathy than in normal subjects, even when macular thickening did not meet the standard for CSMO (p=0.019) measured by biomicroscopy. Although greater fluorescein leakage at the macula results in greater central macular thickness, only eyes with diffuse leakage had statistically significant macular thickening compared with normal subjects (p=0.022). Central macular thickness measured with the RTA was significantly correlated with the logarithmic converted visual acuity (r2= 0.76) in diabetic eyes.
CONCLUSION—Scanning RTA, which has good reproducibility, might be useful to quantitatively detect and monitor macular thickening in diabetic retinopathy. Central macular thickness was highly correlated with logarithmic converted visual acuity in diabetic macular oedema.

 Keywords: scanning retinal thickness analyser; macular

  18. What Is Macular Edema?

    MedlinePlus Videos and Cool Tools

    ... Español Eye Health / Eye Health A-Z Macular Edema Sections What Is Macular Edema? What Causes Macular ... Edema Diagnosis Macular Edema Treatment What Is Macular Edema? Dec. 01, 2010 Macular edema is swelling or ...

  19. Clinical outcomes and mechanism of action for rheopheresis treatment of age-related macular degeneration (AMD).

    PubMed

    Pulido, Jose; Sanders, Donald; Winters, Jeffrey L; Klingel, Reinhard

    2005-10-01

    The primary goals are to provide a comprehensive explanation of the potential role of therapeutic apheresis in the treatment of Age-Related Macular Degeneration (AMD). Initial clinical results with this technique and a summary of current literature that addresses the mechanism of action for the Rheopheresis approach are presented. Rheopheresis has been found to be a safe and effective application of double filtration plasmapheresis (DFPP) for extracorporeal hemorheotherapy. In this report, it is proposed that Rheopheresis results in an immediate decrease in the proportion of high molecular weight proteins that could combine with the TIMP-3 fibulin complex allowing for the barely functioning retinal pigment epithelial (RPE) cells to function better and diminish the release of vascular endothelial growth factor (VEGF). Interim results from the randomized, double-masked MIRA-1 clinical trial include (1) improved vision restoration; 28.0% of Treated Primary Eyes increased by > or = 2 lines of best corrected visual acuity (BCVA) compared to 18.2% of Placebo Eyes; (2) a decline in progressive vision loss; 0.0% of treated eyes progressing to worse than 20/200 vision over the 12-month study compared to 18.2% of Placebo Eyes; (3) 57.9% of Treatment Eyes obtained improvement in their BCVA to 20/40 or better (driver's license qualification), compared to only 14.3% of Placebo Eyes 12-month post-treatment. Rheopheresis treatment shows strong promise as a viable clinical option for patients suffering from the dry form of AMD in terms of minimizing vision loss, vision restoration, and overall quality of life factors. Expanded clinical outcomes from the ongoing MIRA-1 clinical study will be valuable in the assessment of this new clinical tool for ophthalmic applications.

  20. Improving function in age-related macular degeneration: design and methods of a randomized clinical trial.

    PubMed

    Rovner, Barry W; Casten, Robin J; Hegel, Mark T; Massof, Robert W; Leiby, Benjamin E; Tasman, William S

    2011-03-01

    Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD's prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population.

  1. Improving Function in Age-Related Macular Degeneration: Design and Methods of a Randomized Clinical Trial

    PubMed Central

    Rovner, Barry W.; Casten, Robin J.; Hegel, Mark T.; Massof, Robert W.; Leiby, Benjamin E.; Tasman, William S.

    2010-01-01

    Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD’s prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population. PMID:20974293

  2. Macular degeneration

    MedlinePlus Videos and Cool Tools

    ... at the center of the field of vision. Macular degeneration results from a partial breakdown of the insulating ... choroid layer of blood vessels behind the retina. Macular degeneration results in the loss of central vision only.

  3. Intravitreal Bevacizumab with or without Triamcinolone for Refractory Diabetic Macular Edema: Long-term Results of a Clinical Trial

    PubMed Central

    Shoeibi, Nasser; Ahmadieh, Hamid; Entezari, Morteza; Yaseri, Mehdi

    2013-01-01

    Purpose To report the long-term results of intravitreal bevacizumab (IVB) injection alone or combined, at the time of first IVB injection, with intravitreal triamcinolone acetonide (IVT) for treatment of refractory diabetic macular edema (DME). Methods In this randomized clinical trial, 115 eyes of 101 patients with refractory DME were enrolled and randomly assigned to one of the three study arms: the IVB group (41 eyes) received three consecutive injections of 1.25 mg IVB at 6-week intervals; the IVB/IVT group (37 eyes) additionally received 2 mg of IVT at the time of first IVB injection; and the control (sham injection) group. Patients in the IVB and IVB/IVT groups were followed for a mean of 13.3 months and received retreatment with IVB alone whenever indicated. Main outcome measures were best corrected visual acuity (BCVA) and central macular thickness (CMT). Results At the last follow up, CMT decreased significantly in the IVB group (p=0.013) but it was not significant (p=0.13) in the IVB/IVT group. Mean CMT improvement was 91 (95% CI, 20 to 161) microns and 57 (95% CI, -18 to 133) microns in the IVB and IVB/IVT groups, respectively. Mean BCVA improvement from baseline was 0.28 (95% CI, 0.18 to 0.38) logMAR (P=0.017) in the IVB group and 0.19 (95% CI, 0.08 to 0.30) logMAR (P=0.001) in the IVB/IVT group. There was no difference between the two groups in terms of visual improvment (p=0.42). In generalized linear mixed model, only the time interval between the last injection and CMT measurement was statistically significant (P=0.04). The same results were repeated for visual acuity (P=0.03). Conclusion Three loading doses of IVB (added doses if required) have long-term beneficial effects for treatment of refractory DME. Adding triamcinolone to this regimen provides no additional long-term benefit. PMID:23943683

  4. Effect of irradiation on neovascularization in rat skinfold chambers: Implications for clinical trials of low-dose radiotherapy for wet-type age-related macular degeneration

    SciTech Connect

    Hori, Katsuyoshi . E-mail: k-hori@idac.tohoku.ac.jp; Saito, Sachiko; Tamai, Makoto

    2004-12-01

    Purpose: Wet-type age-related macular degeneration is a refractory eye disease that involves choroidal neovascularization. Randomized controlled trials of low-dose radiotherapy for this disease performed in Japan showed that, at 12 months of follow-up, visual acuity was significantly well preserved and the neovascular membrane size decreased. Because understanding the effect of irradiation on new vascular networks is an important prerequisite for clinical trials, we used a rat skinfold chamber technique to investigate X-ray-induced changes in neovasculature microcirculation. Methods and materials: Neovascularization was induced in rat skinfold chambers via polyvinyl chloride resin plates. Neovessels were irradiated in a single 10-Gy dose, after which, changes in vascular density, blood velocity, tissue blood flow, and interstitial fluid pressure (IFP), were measured. Results: Vascular density, tissue blood flow, and IFP measurements in resin-induced inflammatory tissue were much higher than those measurements in normal tissue. Although overall blood velocity was low and sluggish or blood-flow stasis occurred in the neovascular network, after a single 10-Gy dose of radiation, the velocity increased, stasis improved markedly, and many dilated vessels narrowed. Thereafter, vascular density, blood flow, and IFP significantly decreased and approached normal values. Conclusion: These findings may help explain clinical results related to radiotherapy-induced changes in neovascular membranes in age-related macular degeneration. Both vascular morphology and vascular function in inflammatory tissue returned to normal, without vessel destruction, after an appropriate radiation dose.

  5. The use of weighted health-related Quality of Life scores in people with diabetic macular oedema at baseline in a randomized clinical trial

    PubMed Central

    Scanlon, P H; Loftus, J; Starita, C; Stratton, I M

    2015-01-01

    Aims To examine the relationship between visual acuity in each eye and Quality of Life (QoL) outcomes in people with diabetic macular oedema. Methods Cross sectional retrospective analysis of data collected at baseline in 289 people entered into a randomized clinical trial with diabetic macular oedema which investigated the safety and efficacy of a vascular endothelial growth factor inhibitor, pegaptanib sodium. At the baseline visit, visual acuity was measured through refraction and using retro-illuminated modified Early Treatment Diabetic Retinopathy Study Log MAR charts, and patient health-related QoL was determined using the European Quality of Life EQ–5D–3L and the Visual Functioning Questionnaire–25 (NEI–VFQ25). A regression analysis with QoL score from each vision-related domain as the dependent variable was fitted using linear and quadratic terms of the better and worse eye, age, gender, adjusted for number of concurrent conditions, ethnicity and level of diabetes control. Results For all vision-related QoL domains from NEI–VFQ25 and EQ–5D–3L except ocular pain, both visual acuity in the better-seeing and the worse-seeing eye gave a significant increase in correlation coefficient over that obtained from clinical and demographic data. The NEI–VFQ25 correlation was most closely associated with a weighted visual acuity measure of 0.75 in the better and 0.25 in the worse eye or 0.60 in the better and 0.40 in the worse eye. Conclusions We recommend that a weighted visual acuity measure from both eyes is considered in future diabetic macular oedema trials. PMID:25251842

  6. Clinical utility of intravitreal fluocinolone acetonide (Iluvien®) implant in the management of patients with chronic diabetic macular edema: a review of the current literature

    PubMed Central

    Saedon, Habiba; Anand, Astha; Yang, Yit C

    2017-01-01

    The first-line therapy for patients with center-involving diabetic macular edema (DME) is with intravitreal anti-vascular endothelial growth factor (VEGF) agents, with or without adjunctive macular laser treatment. However, a significant proportion of patients have persistent and recurrent edema despite repeated anti-VEGF injections. The fluocinolone acetonide (FA) 190 μg intravitreal implant has been shown in pivotal clinical trials to be efficacious for the treatment of DME and has been approved in many countries for use in patients who have not responded to first-line therapy. In this report, we have collated the latest data from the increasing number of studies to illustrate the pattern of usage of the Iluvien FA implant for DME during the current anti-VEGF era. We have shown that there is now a wealth of published evidence from real-world studies to support the clinical utility of the FA implant in achieving further resolution of edema and improving visual acuity outcomes in this challenging group of patients. PMID:28392675

  7. Statistical significance testing and clinical trials.

    PubMed

    Krause, Merton S

    2011-09-01

    The efficacy of treatments is better expressed for clinical purposes in terms of these treatments' outcome distributions and their overlapping rather than in terms of the statistical significance of these distributions' mean differences, because clinical practice is primarily concerned with the outcome of each individual client rather than with the mean of the variety of outcomes in any group of clients. Reports of the obtained outcome distributions for the comparison groups of all competently designed and executed randomized clinical trials should be publicly available no matter what the statistical significance of the mean differences among these groups, because all of these studies' outcome distributions provide clinically useful information about the efficacy of the treatments compared.

  8. [Pathopshysiological mechanisms in macular edema].

    PubMed

    Turlea, Cristian; Zolog, Ileana; Blăjan, Codruta; Roşca, C; Turlea, Magdalena; Munteanu, Mihnea; Boruga, Ovidiu

    2014-01-01

    The treatment of diabetic macular edema has known a fast development in the last 5 years where the transition from laser monotherapy to intravitreal pharmacotherapy is becoming standard practice. Intravitreal injections therapy is in a continuous development with promising positive results. The use of intratvitreal devices in the treatment of macular edema of vascular cause has become a viable alternative also in treating diabetic macular edema. Several clinical studies have revealed the superiority of intravitreal treatment versus laser monotherapy. This article is evaluating and reviewing present and future treatments used to combat diabetic macular edema. [corrected].

  9. [Macular dystrophies].

    PubMed

    Souied, E; Kaplan, J; Coscas, G; Soubrane, G

    2003-09-01

    Macular dystrophies are a group of hereditary disorders of the macula occurring in children or young adults. The most frequent in France will be presented in detail: Best disease, Stargardt macular dystrophy, cone dystrophy, X-linked retinoschisis, pattern dystrophy, and malattia leventinese. Molecular biology studies have now mapped and identified the genes involved in these macular dystrophies. Analysis of the features of fundus examination will lead to further examinations such as fluorescein angiography, indocyanine green angiography, optical coherent tomography, electroretinography, or electrooculography, in order to confirm the diagnosis. We will also present the differential diagnosis of each of these macular dystrophies.

  10. Macular posterior pigmentary incontinence: its relation to macular amyloidosis and notalgia paresthetica.

    PubMed

    Westermark, P; Ridderström, E; Vahlquist, A

    1996-07-01

    Patients with clinical features of dorsal macular amyloidosis but without subepidermal amyloid deposits were followed for 2-11 years. The clinical appearance was fairly stable during this period of time, with little tendency of healing. Only 2 of the patients developed typical macular amyloidosis during the follow-up. It is concluded that a condition strongly resembling macular amyloidosis but without amyloid is an entity, and the designation "macular posterior pigmentary incontinence" is proposed. The relationship between macular posterior pigmentary incontinence and the two conditions macular amyloidosis and notalgia paresthetica is discussed.

  11. Clinical Characteristics of Patients with Newly Diagnosed Diabetic Macular Edema in Turkey: A Real-Life Registry Study—TURK-DEM

    PubMed Central

    Ozdek, Sengul; Ozmert, Emin; Ulay, Esat; Nomak, Gulsah

    2017-01-01

    Purpose. To evaluate the clinical and diagnostic characteristics of patients with newly diagnosed diabetic macular edema (DME) in Turkey in a real-life setting. Methods. A total of 945 consecutive patients (mean (SD) age: 61.3 (9.9) years, 55.2% male) with newly diagnosed DME were included. Data on patient demographics, comorbidities, ocular history, ophthalmic examination findings including type of DME, central macular thickness (CMT) via time domain (TD) and spectral domain (SD) optical coherence tomography (OCT), and planned treatments were recorded. Results. OCT (98.8%) and fundoscopy (92.9%) were the two most common diagnostic methods. Diffuse and focal DMEs were detected in 39.2% and 36.9% of cases, respectively. Laser photocoagulation (32.1%) and antivascular endothelial growth factors (anti-VEGF; 31.8%) were the most commonly planned treatments. The median CMT in the right eye was significantly greater in untreated than in treated patients [376.5 μm (range: 160–840) versus 342 μm (range: 146–999) (p = 0.002)] and in the left eye [370 μm (range: 201–780) versus 329 μm (range: 148–999) (p < 0.001)]. Conclusions. This study is the first large-scale real-life registry of DME patients in Turkey. SD-OCT and fundoscopy were the most common diagnostic methods. Laser photocoagulation and anti-VEGF therapy were the most common treatments. PMID:28316835

  12. Clinically significant drug interactions with atypical antipsychotics.

    PubMed

    Kennedy, William Klugh; Jann, Michael W; Kutscher, Eric C

    2013-12-01

    Atypical antipsychotics [also known as second-generation antipsychotics (SGAs)] have become a mainstay therapeutic treatment intervention for patients with schizophrenia, bipolar disorders and other psychotic conditions. These agents are commonly used with other medications--most notably, antidepressants and antiepileptic drugs. Drug interactions can take place by various pharmacokinetic, pharmacodynamic and pharmaceutical mechanisms. The pharmacokinetic profile of each SGA, especially with phase I and phase II metabolism, can allow for potentially significant drug interactions. Pharmacodynamic interactions arise when agents have comparable receptor site activity, which can lead to additive or competitive effects without alterations in measured plasma drug concentrations. Additionally, the role of drug transporters in drug interactions continues to evolve and may effect both pharmacokinetic and pharmacodynamic interactions. Pharmaceutical interactions occur when physical incompatibilities take place between agents prior to drug absorption. Approximate therapeutic plasma concentration ranges have been suggested for a number of SGAs. Drug interactions that markedly increase or decrease the concentrations of these agents beyond their ranges can lead to adverse events or diminished clinical efficacy. Most clinically significant drug interactions with SGAs occur via the cytochrome P450 (CYP) system. Many but not all drug interactions with SGAs are identified during drug discovery and pre-clinical development by employing a series of standardized in vitro and in vivo studies with known CYP inducers and inhibitors. Later therapeutic drug monitoring programmes, clinical studies and case reports offer methods to identify additional clinically significant drug interactions. Some commonly co-administered drugs with a significant potential for drug-drug interactions with selected SGAs include some SSRIs. Antiepileptic mood stabilizers such as carbamazepine and valproate, as

  13. A Phase 2 Randomized Clinical Trial of Intravitreal Bevacizumab for Diabetic Macular Edema

    PubMed Central

    2008-01-01

    Objective To provide data on the short-term effect of intravitreal bevacizumab for diabetic macular edema (DME). Design Randomized phase 2 clinical trial. Participants 121 eyes of 121 subjects (109 eligible for analysis) with DME and Snellen acuity equivalent ranging from 20/32-20/320. Interventions Random assignment to one of five groups: focal photocoagulation at baseline (N=19, Group A), intravitreal injection of 1.25mg bevacizumab at baseline and 6 weeks (N=22, Group B), intravitreal injection of 2.5mg bevacizumab at baseline and 6 weeks (N=24, Group C), intravitreal injection of 1.25mg bevacizumab at baseline and sham injection at 6 weeks (N=22, Group D), or intravitreal injection of 1.25mg bevacizumab at baseline and 6 weeks with photocoagulation at 3 weeks (N=22, Group E). Main Outcome Measures Central subfield thickness (CST) on optical coherence tomography and best-corrected visual acuity (VA) were measured at baseline and after 3, 6, 9, 12, 18, and 24 weeks. Results At baseline, median CST was 411 microns and median Snellen VA equivalent was 20/50. Compared with Group A, Groups B and C had a greater reduction in CST at 3 weeks and about one line better median visual acuity over 12 weeks. There were no meaningful differences between Groups B and C in CST reduction or VA improvement. A CST reduction >11% (the reliability limit) was present at 3 weeks in 36/84 (43%) bevacizumab-treated eyes and in 5/18 (28%) eyes treated with laser alone, and at 6 weeks in 31/84 (37%) and 9/18 (50%) eyes, respectively. Combining focal photocoagulation with bevacizumab resulted in no apparent short-term benefit or adverse outcomes. Endophthalmitis developed in one eye. The following events occurred during the first 24 weeks in subjects treated with bevacizumab without attributing cause to the drug: myocardial infarction (N=2), congestive heart failure (N=1), elevated blood pressure (N=3), and worsened renal function (N=3). Conclusion These results demonstrate that

  14. Are Carotid Stent Fractures Clinically Significant?

    SciTech Connect

    Garcia-Toca, Manuel; Rodriguez, Heron E.; Naughton, Peter A.; Keeling, Aiofee; Phade, Sachin V.; Morasch, Mark D.; Kibbe, Melina R.; Eskandari, Mark K.

    2012-04-15

    Purpose: Late stent fatigue is a known complication after carotid artery stenting (CAS) for cervical carotid occlusive disease. The purpose of this study was to determine the prevalence and clinical significance of carotid stent fractures. Materials and Methods: A single-center retrospective review of 253 carotid bifurcation lesions treated with CAS and mechanical embolic protection from April 2001 to December 2009 was performed. Stent integrity was analyzed by two independent observers using multiplanar cervical plain radiographs with fractures classified into the following types: type I = single strut fracture; type II = multiple strut fractures; type III = transverse fracture; and type IV = transverse fracture with dislocation. Mean follow-up was 32 months. Results: Follow-up imaging was completed on 106 self-expanding nitinol stents (26 closed-cell and 80 open-cell stents). Eight fractures (7.5%) were detected (type I n = 1, type II n = 6, and type III n = 1). Seven fractures were found in open-cell stents (Precise n = 3, ViVEXX n = 2, and Acculink n = 2), and 1 fracture was found in a closed-cell stent (Xact n = 1) (p = 0.67). Only a previous history of external beam neck irradiation was associated with fractures (p = 0.048). No associated clinical sequelae were observed among the patients with fractures, and only 1 patient had an associated significant restenosis ({>=}80%) requiring reintervention. Conclusions: Late stent fatigue after CAS is an uncommon event and rarely clinically relevant. Although cell design does not appear to influence the occurrence of fractures, lesion characteristics may be associated risk factors.

  15. Quantifying the Clinical Significance of Cannabis Withdrawal

    PubMed Central

    Allsop, David J.; Copeland, Jan; Norberg, Melissa M.; Fu, Shanlin; Molnar, Anna; Lewis, John; Budney, Alan J.

    2012-01-01

    Background and Aims Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt. Methods and Results A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001). Conclusions Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes. PMID:23049760

  16. Clinically significant drug interactions with newer antidepressants.

    PubMed

    Spina, Edoardo; Trifirò, Gianluca; Caraci, Filippo

    2012-01-01

    After the introduction of selective serotonin reuptake inhibitors (SSRIs), other newer antidepressants with different mechanisms of action have been introduced in clinical practice. Because antidepressants are commonly prescribed in combination with other medications used to treat co-morbid psychiatric or somatic disorders, they are likely to be involved in clinically significant drug interactions. This review examines the drug interaction profiles of the following newer antidepressants: escitalopram, venlafaxine, desvenlafaxine, duloxetine, milnacipran, mirtazapine, reboxetine, bupropion, agomelatine and vilazodone. In general, by virtue of a more selective mechanism of action and receptor profile, newer antidepressants carry a relatively low risk for pharmacodynamic drug interactions, at least as compared with first-generation antidepressants, i.e. monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). On the other hand, they are susceptible to pharmacokinetic drug interactions. All new antidepressants are extensively metabolized in the liver by cytochrome P450 (CYP) isoenzymes, and therefore may be the target of metabolically based drug interactions. Concomitant administration of inhibitors or inducers of the CYP isoenzymes involved in the biotransformation of specific antidepressants may cause changes in their plasma concentrations. However, due to their relatively wide margin of safety, the consequences of such kinetic modifications are usually not clinically relevant. Conversely, some newer antidepressants may cause pharmacokinetic interactions through their ability to inhibit specific CYPs. With regard to this, duloxetine and bupropion are moderate inhibitors of CYP2D6. Therefore, potentially harmful drug interactions may occur when they are coadministered with substrates of these isoforms, especially compounds with a narrow therapeutic index. The other new antidepressants are only weak inhibitors or are not inhibitors of CYP isoforms at

  17. Clinical significance of MET in gastric cancer

    PubMed Central

    Inokuchi, Mikito; Otsuki, Sho; Fujimori, Yoshitaka; Sato, Yuya; Nakagawa, Masatoshi; Kojima, Kazuyuki

    2015-01-01

    Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC. Hepatocyte growth factor and its receptor, c-MET (MET), play key roles in tumor growth through activated signaling pathways from receptor in GC cells. Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC. Preclinical studies in animal models have shown that MET antibodies or small-molecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells. These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC. PMID:26600931

  18. Age-Related Macular Degeneration: Clinical Findings following Treatment with Antiangiogenic Drugs.

    PubMed

    Casaroli-Marano, Ricardo; Gallego-Pinazo, Roberto; Fernández-Blanco, Clemencia Torrón; Figueroa, Marta S; Pina Marín, Begoña; Fernández-Baca Vaca, Gustavo; Piñero-Bustamante, Antonio; Donate López, Juan; García-Arumí, José; Farrés Martí, Jordi

    2014-01-01

    Purpose. To survey the management of patients with neovascular age-related macular degeneration (nvAMD) in Spain. Methods. An observational retrospective multicenter study was conducted. The variables analyzed were sociodemographic characteristics, foveal and macular thickness, visual acuity (VA), type of treatment, number of injections, and the initial administration of a loading dose of an antiangiogenic drug. Results. 208 patients were followed up during 23.4 months in average. During the first and second years, patients received a mean of 4.5 ± 1.8 and 1.6 ± 2.1 injections of antiangiogenic drugs, and 5.4 ± 2.8 and 3.6 ± 2.2 follow-up visits were performed, respectively. The highest improvement in VA was observed at 3 months of follow-up, followed by a decrease in the response that stabilized above baseline values until the end of the study. Patients who received an initial loading dose presented greater VA gains than those without. Conclusions. Our results suggest the need for a more standardized approach in the management and diagnosis of nvAMD receiving VEGF inhibitors. To achieve the visual outcomes reported in pivotal trials, an early diagnosis, proactive approach (more treating than follow-up visits), and a close monitoring might be the key to successfully manage nvAMD.

  19. Assessing quality of life in the treatment of patients with age-related macular degeneration: clinical research findings and recommendations for clinical practice

    PubMed Central

    Yuzawa, Mitsuko; Fujita, Kyoko; Tanaka, Erika; Wang, Edward C Y

    2013-01-01

    Background The importance of incorporating quality-of-life (QoL) assessments into medical practice is growing as health care practice shifts from a “disease-based” to a “patient-centered” model. The prevalence of age-related macular degeneration (AMD) is increasing in today’s aging population. The purpose of this paper is: (1) to discuss, by reviewing the current literature, the impact of AMD on patients’ QoL and the utility of QoL assessments in evaluating the impact of AMD and its treatment; and (2) to make a recommendation for incorporating QoL into clinical practice. Methods We conducted a PubMed and an open Internet search to identify publications on the measurement of QoL in AMD, as well as the impact of AMD and the effect of treatment on QoL. A total of 28 articles were selected. Results AMD has been found to cause a severity-dependent decrement in QoL that is comparable to systemic diseases such as cancer, ischemic heart disease, and stroke. QoL impairment manifests as greater social dependence, difficulty with daily living, higher rates of clinical depression, increased risk of falls, premature admission to nursing homes, and suicide. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) is the most widely used eye disease-specific QoL instrument in AMD. It has been shown to correlate significantly with visual acuity (VA). QoL reflects aspects of AMD including psychological well-being, functional capacity, and the ability to perform patients’ valued activities, which are not captured by a single, numerical VA score. Conclusion The literature shows that the adverse impact of AMD on QoL is comparable to serious systemic disease. Eye disease-specific instruments for measuring QoL, such as the NEI VFQ-25, have shown a significant correlation of QoL decrement with measures of disease severity, as well as significant QoL improvement with treatment. The NEI VFQ-25 and other validated instruments provide a wide-ranging assessment

  20. AEG-1/MTDH/LYRIC: Clinical Significance

    PubMed Central

    Sarkar, Devanand; Fisher, Paul B.

    2014-01-01

    “Gain-of-function” and “loss-of-function” studies in human cancer cells and analysis of a transgenic mouse model have convincingly established that AEG-1/MTDH/LYRIC performs a seminal role in regulating proliferation, invasion, angiogenesis, metastasis, and chemoresistance, the salient defining hallmarks of cancer. These observations are strongly buttressed by clinicopathologic correlations of AEG-1/MTDH/LYRIC expression in a diverse array of cancers distinguishing AEG-1/MTDH/LYRIC as an independent biomarker for highly aggressive metastatic disease with poor prognosis. AEG-1/MTDH/LYRIC has been shown to be a marker predicting response to chemotherapy, and serum anti-AEG-1/MTDH/LYRIC antibody titer also serves as a predictor of advanced stages of aggressive cancer. However, inconsistent findings have been reported regarding the localization of AEG-1/MTDH/LYRIC protein in the nucleus or cytoplasm of cancer cells and the utility of nuclear or cytoplasmic AEG-1/MTDH/LYRIC to predict the course and prognosis of disease. This chapter provides a comprehensive analysis of the existing literature to emphasize the common and conflicting findings relative to the clinical significance of AEG-1/MTDH/LYRIC in cancer. PMID:23889987

  1. Clinical significance of epithelial-mesenchymal transition

    PubMed Central

    2014-01-01

    The concept of epithelial-mesenchymal transition (EMT), a process where cells change their epithelial towards a mesenchymal phenotype, has gained overwhelming attention especially in the cancer research community. Thousands of scientific reports investigated changes in gene, mRNA and protein expression compatible with EMT and their possible correlation with tumor invasion, metastatic spread or patient prognosis; however, up to now, a proof of clinical significance of the concept is still missing. This review, with a main focus on the role of EMT in tumors, will summarize the basic molecular events underlying EMT including the signaling pathways capable of its induction as well as changes in EMT-associated protein expression and will very briefly touch the role of microRNAs in EMT. We then outline protein markers that are used most frequently for the assessment of EMT in research and diagnostic evaluation of tumor specimens and depict the link between EMT, a cancer stem cell (CSC) phenotype and resistance to conventional antineoplastic therapies. Furthermore, we evaluate a possible correlation between EMT marker expression and patient prognosis as well as current therapeutic concepts targeting the EMT process to slow down or prevent metastatic spread of malignant tumors. PMID:25050175

  2. Significance of FISH in clinical cytogenetics

    SciTech Connect

    Gopal Rao, V.V.N.; Harris, S.; Roop, H.

    1994-09-01

    Ever since its discovery, FISH technology has become an invaluable adjunct to conventional cytogenetics. FISH has been instrumental in resolving previously unresolved cytogenetic dilemmas. FISH has been used to elucidate complex as well as subtle chromosomal translocations, in detection of microdeletions, to confirm duplications and inversions and to identify marker chromosomes. We report a few selected cases where FISH proved to be invaluable in not only confirming the anomaly, but also in arriving at an accurate diagnosis and appropriate counseling of the patients. These include 3 cases of prenatal and 3 cases of postnatal diagnosis. The results clearly demonstrate the significance of FISH in identifying and interpreting the difficult karyotype in clinical cytogenetics. In addition, FISH has been used to rule out microdeletions in Prader-Willi (16), Angelman (3), Miller-Dieker (7), DiGeorge (4) and Smith-Magenis (1) syndrome patients. Without FISH in the majority of these cases, it would not have been possible to accurately identify the karyotype and interpret the results. Hence, we recommend that FISH be used as a powerful adjunct to conventional cytogenetics in order to arrive at an accurate interpretation of the results but not to replace routine cytogenetic studies.

  3. Photodynamic Therapy and Intravitreal Bevacizumab with Versus without Triamcinolone for Neovascular Age-related Macular Degeneration; a Randomized Clinical Trial

    PubMed Central

    Piri, Niloofar; Ahmadieh, Hamid; Taei, Ramin; Soheilian, Masoud; Karkhaneh, Reza; Lashay, Alireza; Golbafian, Faegheh; Yaseri, Mehdi; Riazi-Esfahani, Mohammad

    2014-01-01

    Purpose: To compare the outcomes of photodynamic therapy (PDT) combined with intravitreal bevacizumab (IVB) with versus without intravitreal triamcinolone (IVT) in neovascular age-related macular degeneration (AMD). Methods: Eighty-four eyes with active CNV secondary to AMD with no prior treatment were enrolled and followed for 1-year. Eligible eyes were randomly assigned to either PDT/IVB or PDT/IVB/IVT. The main outcome measure was change in best-corrected visual acuity (BCVA). Results: Mean patient age was 71 ± 9 years. BCVA changes from baseline were statistically significant in both study arms at all follow-up intervals, however no significant difference was observed between the two groups regarding BCVA changes at week 12 (95% CI:-0.11–0.12 LogMAR) and other time points (all P > 0.6). Mixed model analysis revealed a significant effect from age (P < 0.001), pigment epithelial detachment (P = 0.009) and baseline BCVA (P < 0.001) on visual improvement. Significant central macular thickness (CMT) reduction occurred at all-time points as compared to baseline in both groups which was comparable between the study arms. There was no significant difference between the study arms in terms of retreatment rate (P = 0.1) and survival to the first repeat IVB injection (P = 0.065). Conclusion: Additional low-dose IVT to a PDT/IVB regimen for neovascular AMD provided no beneficial effects in terms BCVA or CMT, yet demonstrated a trend toward extending the injection-free period. PMID:25709773

  4. Influence of Clinical Factors and Magnification Correction on Normal Thickness Profiles of Macular Retinal Layers Using Optical Coherence Tomography

    PubMed Central

    Higashide, Tomomi; Ohkubo, Shinji; Hangai, Masanori; Ito, Yasuki; Shimada, Noriaki; Ohno-Matsui, Kyoko; Terasaki, Hiroko; Sugiyama, Kazuhisa; Chew, Paul; Li, Kenneth K. W.; Yoshimura, Nagahisa

    2016-01-01

    Purpose To identify the factors which significantly contribute to the thickness variabilities in macular retinal layers measured by optical coherence tomography with or without magnification correction of analytical areas in normal subjects. Methods The thickness of retinal layers {retinal nerve fiber layer (RNFL), ganglion cell layer plus inner plexiform layer (GCLIPL), RNFL plus GCLIPL (ganglion cell complex, GCC), total retina, total retina minus GCC (outer retina)} were measured by macular scans (RS-3000, NIDEK) in 202 eyes of 202 normal Asian subjects aged 20 to 60 years. The analytical areas were defined by three concentric circles (1-, 3- and 6-mm nominal diameters) with or without magnification correction. For each layer thickness, a semipartial correlation (sr) was calculated for explanatory variables including age, gender, axial length, corneal curvature, and signal strength index. Results Outer retinal thickness was significantly thinner in females than in males (sr2, 0.07 to 0.13) regardless of analytical areas or magnification correction. Without magnification correction, axial length had a significant positive sr with RNFL (sr2, 0.12 to 0.33) and a negative sr with GCLIPL (sr2, 0.22 to 0.31), GCC (sr2, 0.03 to 0.17), total retina (sr2, 0.07 to 0.17) and outer retina (sr2, 0.16 to 0.29) in multiple analytical areas. The significant sr in RNFL, GCLIPL and GCC became mostly insignificant following magnification correction. Conclusions The strong correlation between the thickness of inner retinal layers and axial length appeared to result from magnification effects. Outer retinal thickness may differ by gender and axial length independently of magnification correction. PMID:26814541

  5. Clinical significance of autoantibodies in autoimmune hepatitis.

    PubMed

    Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego

    2013-10-01

    The accurate diagnosis and classification of autoimmune hepatitis (AIH) rely upon the detection of characteristic autoantibodies. Positivity for anti-nuclear (ANA) and/or anti-smooth muscle (SMA) autoantibodies defines AIH type 1 (AIH-1), whereas anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) define AIH type 2 (AIH-2). ANA and SMA, and less commonly anti-LKM1, have also been detected in de-novo autoimmune hepatitis developing after liver transplantation, a condition that may affect patients transplanted for non-autoimmune liver disease. The diagnostic autoantibodies associated with AIH-1 are also detected in the paediatric AIH/sclerosing cholangitis overlap syndrome, referred to as autoimmune sclerosing cholangitis (ASC). ASC, like adult primary sclerosing cholangitis, is often associated with atypical perinuclear anti-neutrophil cytoplasmic autoantibodies (p-ANCA), although p-ANCA are also detected in other autoimmune liver diseases. These associations highlight the necessity for simple and prompt diagnostic autoantibody testing, and the requirement for the accurate interpretation of the results of the tests in the clinical context. Fine-mapping of antigenic autoantibody targets has facilitated the development of rapid molecular assays that have the potential to revolutionise the field if properly standardised and when used in combination with classical immunofluorescence. Despite their diagnostic significance, the pathogenic role of the various autoantibodies and the mechanisms by which they can potentially inflict damage onto the liver cell remain a topic for further research.

  6. Bromfenac 0.09% bioavailability in aqueous humor, prophylactic effect on cystoid macular edema, and clinical signs of ocular inflammation after phacoemulsification in a Mexican population

    PubMed Central

    Palacio, Claudia; Fernández De Ortega, Lourdes; Bustos, Francisco R; Chávez, Eduardo; Oregon-Miranda, Aldo A; Mercado-Sesma, Arieh R

    2016-01-01

    Purpose The purpose of this study was to evaluate the aqueous humor bioavailability and clinical efficacy of bromfenac 0.09% vs nepafenac on the presence of cystoid macular edema (CME) after phacoemulsification. Material and methods A Phase II, double-blind, masked, active-controlled, multicenter, clinical trial of 139 subjects, randomized to either a bromfenac 0.09% ophthalmic solution (n=69) or nepafenac 0.1% (n=70). Subjects instilled a drop three times a day for a period of 30 days. Follow-up visits were on days 2, 7, 15, 30, and 60. Biomicroscopy, clinical ocular signs, and assessment of posterior segment were performed. The primary efficacy endpoints included the presence of CME evaluated by optical coherence tomography. Safety evaluation included intraocular pressure, transaminase enzymes, lissamine green, and fluorescein stain. Results The demographic and efficacy variables were similar between groups at baseline. The presence of pain, photophobia, conjunctival hyperemia, chemosis, cellularity, and corneal edema disappeared by day 30 in both groups. The central retinal thickness did not show significant changes after treatment when compared to baseline as follows: in the bromfenac group (247.2±32.9 vs 252.0±24.9 μm; P=0.958) and in nepafenac group (250.8±34 vs 264.0±34.1 μm; P=0.137), respectively. A statistically significant difference was observed between bromfenac and nepafenac group: (252.0±24.9 vs 264.0±34.1 μm; P=0.022), at day 30, respectively; even though there was no clinical relevance in the presentation of CME. There were no significant alterations in intraocular pressure, either lissamine green or fluorescein stains. The adverse events were not related to the interventions. Conclusion Bromfenac 0.09% ophthalmic solution showed similar clinical efficacy to reduce the presentation of CME after phacoemulsification compared to nepafenac 0.01%. PMID:26869758

  7. [The significance of biobanks for clinical development].

    PubMed

    Thomas, Marlene; Kiermaier, Astrid; Cannarile, Michael

    2016-03-01

    Access to samples in biobanks and collection of samples for evaluation of biomarkers in clinical trials are an essential basis for the identification and development of biomarkers. From the perspective of a research-based pharmaceutical company identification of biomarkers and the accompanying diagnostics are an essential prerequisite for the further evolution of personalised healthcare-and the key to more effective and efficient healthcare. Research-based pharmaceutical companies can basically use four types of biobanks: biobanks of university hospitals, commercial providers, collaborative groups and company-owned biobanks. Areas of application, arising from the use of biobanks in the context of clinical development, are collection of prevalence data, evaluation of biomarker stability in different disease stages, technical validation of assays, an optimized course of clinical studies by focusing on defined, biomarker-stratified groups of patients and pharmacogenetic research. Challenges are, in particular, the availability of clinically annotated samples and tissue matching blood samples, in addition to sample quality, number and amount. An acceptable legal and regulatory framework, as well as the positive perception of biomarker data by politicians and the public, are important prerequisites for translational research for identification of biomarkers in clinical studies. Also, the early establishment of research alliances between academia and the pharmaceutical industry are required to transfer research results in new strategies for prevention, diagnosis and treatment of patients.

  8. The clinical significance of pancreatic steatosis.

    PubMed

    Smits, Mark M; van Geenen, Erwin J M

    2011-03-01

    More research is now focused on pancreatic steatosis. Multiple definitions, clinical associations and synonyms for pancreatic steatosis are described in the literature and can be confusing. The integration and comparison of several studies concerning this topic is therefore challenging. In the past, pancreatic steatosis was considered an innocuous condition, a bystander of many underlying diseases (such as congenital syndromes, hemochromatosis and viral infection). However, evidence that pancreatic steatosis (strongly associated with obesity and the metabolic syndrome) has a role in type 2 diabetes mellitus, pancreatic exocrine dysfunction, acute pancreatitis, pancreatic cancer and the formation of pancreatic fistula after pancreatic surgery is emerging. This Review focuses on the different etiological factors and the clinical consequences of pancreatic steatosis.

  9. [Neuroplasticity: main mechanisms and their clinical significance].

    PubMed

    Damulin, I V

    2009-01-01

    Common mechanisms of neuroplasticity and their manifestations in different neurological diseases are reviewed. The ambiguity of physiological and clinical changes caused by neuroplasticity is emphasized. Special attention is drawn to the functional post-stroke rehabilitation. The author emphasizes the importance of "cerebral reserve" in normal ageing and Alzheimer's disease. Possibilities of neuroplasticity activation are reviewed. The efficacy of cerebrolysin in the treatment of dementia and stroke is mentioned.

  10. Clinical significance of feline heartworm disease.

    PubMed

    Dillon, R

    1998-11-01

    The clinical signs and diagnostic approach are different in the cat as compared with the dog, which has impaired the veterinarian's ability to detect this parasite in the cat. New techniques and methodologies have enabled the cat owner and veterinarian to recognize this potentially severe disease. Although much is now known about the pathophysiology and biology of this parasite in the cat, the practical application and rapid development of this information to daily practice has led to confusion.

  11. Macular thickness and macular volume measurements using spectral domain optical coherence tomography in normal Nepalese eyes

    PubMed Central

    Pokharel, Amrit; Shrestha, Gauri Shankar; Shrestha, Jyoti Baba

    2016-01-01

    Purpose To record the normative values for macular thickness and macular volume in normal Nepalese eyes. Methods In all, 126 eyes of 63 emmetropic subjects (mean age: 21.17±6.76 years; range: 10–37 years) were assessed for macular thickness and macular volume, using spectral domain-optical coherence tomography over 6×6 mm2 in the posterior pole. A fast macular thickness protocol was employed. Statistics such as the mean, median, standard deviation, percentiles, and range were used, while a P-value was set at 0.05 to test significance. Results Average macular thickness and total macular volume were larger in males compared to females. With each year of increasing age, these variables decreased by 0.556 μm and 0.0156 mm3 for average macular thickness and total macular volume, respectively. The macular thickness was greatest in the inner superior section and lowest at the center of the fovea. The volume was greatest in the outer nasal section and thinnest in the fovea. The central subfield thickness (r=−0.243, P=0.055) and foveal volume (r=0.216, P=0.09) did not correlate with age. Conclusion Males and females differ significantly with regard to macular thickness and macular volume measurements. Reports by other studies that the increase in axial length reduced thickness and volume, were negated by this study which found a positive correlation among axial length, thickness, and volume. PMID:27041990

  12. [Coat color in dogs. 2: Clinical significance].

    PubMed

    Laukner, A

    1998-04-01

    The meaning of the coat colour of the dog reaches further than only to the field of breeding for beauty. Besides aspects of destination (hunting dogs, herding dogs) the clinical meaning is of particular interest. Some colours can show certain defects. Diseases of allowed colours are the colour dilution alopecia (CDA) in diluted (mostly "blue") pigmentation with its subtype of Black hair follicular dysplasia (BHFD) in black pigmentation and congenital deafness in extreme piebalds. Not allowed coat colours, which are connected with defects, are the extreme dapple of the Merle-syndrome and the "grey" Collie with cyclic hematopoesis.

  13. Vasa Vasorum in Atherosclerosis and Clinical Significance

    PubMed Central

    Xu, Junyan; Lu, Xiaotong; Shi, Guo-Ping

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease that leads to several acute cardiovascular complications with poor prognosis. For decades, the role of the adventitial vasa vasorum (VV) in the initiation and progression of atherosclerosis has received broad attention. The presence of VV neovascularization precedes the apparent symptoms of clinical atherosclerosis. VV also mediates inflammatory cell infiltration, intimal thickening, intraplaque hemorrhage, and subsequent atherothrombosis that results in stroke or myocardial infarction. Intraplaque neovessels originating from VV can be immature and hence susceptible to leakage, and are thus regarded as the leading cause of intraplaque hemorrhage. Evidence supports VV as a new surrogate target of atherosclerosis evaluation and treatment. This review provides an overview into the relationship between VV and atherosclerosis, including the anatomy and function of VV, the stimuli of VV neovascularization, and the available underlying mechanisms that lead to poor prognosis. We also summarize translational researches on VV imaging modalities and potential therapies that target VV neovascularization or its stimuli. PMID:26006236

  14. The clinical significance of occult HBV infection

    PubMed Central

    Squadrito, Giovanni; Spinella, Rosaria; Raimondo, Giovanni

    2014-01-01

    The presence of hepatitis B virus (HBV) DNA in HBV surface antigen (HBsAg)-negative individuals is defined as occult HBV infection (OBI). OBI is related in some cases to infection with variant viruses (S-escape mutants) undetectable by HBsAg commercial kits. More frequently, however, it is due to infection with wild-type viruses that are strongly suppressed in their replication activity. OBI may be involved in different clinical contexts, including the transmission of the infection by blood transfusion or liver transplantation and its acute reactivation when an immunosuppressive status occurs. Moreover, much evidence suggests that it may contribute to the development of cirrhosis and may have an important role in hepatocarcinogenesis. PMID:24714731

  15. The clinical significance of command hallucinations.

    PubMed

    Hellerstein, D; Frosch, W; Koenigsberg, H W

    1987-02-01

    Patients with command hallucinations (voices ordering particular acts, often violent or destructive ones) are commonly assumed to be at high risk for dangerous behavior. The authors reviewed 789 consecutive inpatient admissions. Of 151 patients with auditory hallucinations, 58 (38.4%) heard commands. The presence of auditory hallucinations was significantly associated with diagnosis, demographic variables, and use of maximal observation and seclusion. However, patients with command hallucinations were not significantly different from patients without commands on demographic and behavioral variables, including suicidal ideation or behavior and assaultiveness. These findings suggest that command hallucinations alone may not imply greater risk for acute, life-threatening behavior.

  16. Macular degeneration (image)

    MedlinePlus

    Macular degeneration is a disease of the retina that affects the macula in the back of the eye. ... see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more ...

  17. [Base excess. Parameter with exceptional clinical significance].

    PubMed

    Schaffartzik, W

    2007-05-01

    The base excess of blood (BE) plays an important role in the description of the acid-base status of a patient and is gaining in clinical interest. Apart from the Quick test, the age, the injury severity score and the Glasgow coma scale, the BE is becoming more and more important to identify, e. g. the risk of mortality for patients with multiple injuries. According to Zander the BE is calculated using the pH, pCO(2), haemoglobin concentration and the oxygen saturation of haemoglobin (sO(2)). The use of sO(2 )allows the blood gas analyser to determine only one value of BE, independent of the type of blood sample analyzed: arterial, mixed venous or venous. The BE and measurement of the lactate concentration (cLac) play an important role in diagnosing critically ill patients. In general, the change in BE corresponds to the change in cLac. If DeltaBE is smaller than DeltacLac the reason could be therapy with HCO(3)(-) but also with infusion solutions containing lactate. Physician are very familiar with the term BE, therefore, knowledge about an alkalizing or acidifying effect of an infusion solution would be very helpful in the treatment of patients, especially critically ill patients. Unfortunately, at present the description of an infusion solution with respect to BE has not yet been accepted by the manufacturers.

  18. Age-related macular degeneration: clinical findings, histopathology and imaging techniques.

    PubMed

    Zarbin, Marco A; Casaroli-Marano, Ricardo P; Rosenfeld, Philip J

    2014-01-01

    Age-related macular degeneration (AMD) is the most common cause of blindness among people over age 55 years in industrialized countries. Known major risk factors for AMD include: age >55 years, history of smoking, white race, and mutations in various components of the complement system. Early AMD is characterized by the presence of drusen and pigmentary abnormalities. Late AMD is associated with central visual loss and is characterized by the presence of choroidal neovascularization and/or geographic atrophy. Early AMD is associated with a number of biochemical abnormalities including oxidative damage to retinal pigment epithelium (RPE) cells, complement deposition in the RPE-Bruch's membrane-choriocapillaris complex, lipidization of Bruch's membrane, and extracellular matrix abnormalities (e.g. collagen crosslinking, advanced glycation end product formation). Antiangiogenic drugs block the vascular leakage associated with choroidal new vessels, thus reducing retinal edema and stabilizing or restoring vision. At this time, there are no proven effective treatments for the nonexudative complications of AMD. Modern ocular imaging technologies (including spectral domain and phase variance optical coherence tomography, short- and long-wavelength fundus autofluorescence, adaptive optics-scanning laser ophthalmoscopy, and near-infrared reflectance) enable one to follow changes in the RPE, photoreceptors, and choriocapillaris quantitatively as the disease progresses. In addition, one can quantitatively assess the volume of drusen and areas of atrophy. These data, when correlated with the known histopathology of AMD, may provide useful measures of treatment efficacy that are likely to be more sensitive and reproducible than conventional end points such as visual acuity and rate of enlargement of geographic atrophy. As a result, these imaging technologies may be valuable in assessing the effects of cell-based therapy for patients with AMD.

  19. Clinical Significance and Pathogenesis of Osteoporosis*

    PubMed Central

    Nordin, B. E. C.

    1971-01-01

    The development of osteoporosis with advancing age in man is a widespread if not a universal phenomenon. The average loss between youth and old age amounts to about 15% of the skeleton but involves a much larger proportion of trabecular than of cortical bone. The principal clinical manifestation of osteoporosis is fracture, and three osteoporotic fracture syndromes can be defined: the lower forearm fracture, which predominantly affects women between the ages of 50 and 65; the fracture of the proximal femur, which affects both sexes over the age of 70; and the relatively rare vertebral crush fracture syndrome, which may present at any age but is most common in elderly women. The lower forearm fracture rate is inversely related to the mean normal lower forearm x-ray “density” of the wrist, which falls by about 30% in the 15 years following the menopause. This process, which is associated with corresponding trabecular bone loss elsewhere in the skeleton, is associated with a corresponding rise in the fasting urinary calcium excretion. Some degree of negative calcium balance, and consequent bone resorption, probably occurs in everyone during the later part of the night because calcium absorption is completed within about three to five hours of a meal. In postmenopausal women, however, the sensitivity of the bone to parathyroid hormone appears to be increased, and their nocturnal negative calcium balance therefore comes to exceed the positive balance which can be achieved during the waking hours. Femoral neck fractures in old people reflect the further progression of osteoporosis with advancing age since the fracture rate is inversely correlated with the mean thickness of the metacarpal cortex in the normal population. This progressive osteoporosis is associated with and could well result from a steady decline in calcium absorption which is at least partially attributable to vitamin-D deficiency and reversible on vitamin-D treatment. The vertebral crush fracture

  20. Anti-VEGF treatment of diabetic macular edema in clinical practice: effectiveness and patterns of use (ECHO Study Report 1)

    PubMed Central

    Blinder, Kevin J; Dugel, Pravin U; Chen, Sanford; Jumper, J Michael; Walt, John G; Hollander, David A; Scott, Lanita C

    2017-01-01

    Purpose To evaluate the efficacy, safety, and injection frequency of vascular endothelial growth factor (VEGF) inhibitors as used in clinical practice for the treatment of diabetic macular edema. Methods Multicenter (10 sites), retrospective chart review in patients (n=156) who received ≥3 anti-VEGF injections. Data collected for ≥6 months after the first injection included Snellen best-corrected visual acuity (BCVA) and central retinal thickness (CRT) by time-domain or spectral-domain optical coherence tomography (TD-OCT or SD-OCT). Results Mean number of anti-VEGF injections (627 bevacizumab, 594 ranibizumab, 1 aflibercept) was 5.8 (year 1), 5.0 (year 2), and 3.4 (year 3). Percentage of patients with BCVA of 20/40 or better and CRT ≤250 μm on TD-OCT or ≤300 μm on SD-OCT at the same visit (primary endpoint) ranged from 16.4% to 38.9% after the first 10 injections; 51.9%–62.3% achieved ≥20/40 BCVA and 26.2%–48.0% met CRT criteria. Therapy was well tolerated with 19 treatment-related adverse events (all ocular) reported. Conclusion Anti-VEGF injections were administered less frequently and were less effective than those in the ranibizumab registration trials. After each of the first 9 injections, <25% of patients achieved both BCVA of 20/40 or better and a dry macula. A substantial proportion of patients are suboptimal responders to anti-VEGF therapy; these patients may be candidates for other therapies, including intravitreal corticosteroid and laser therapy. PMID:28260851

  1. Association of age-related macular degeneration and reticular macular disease with cardiovascular disease.

    PubMed

    Rastogi, Neelesh; Smith, R Theodore

    2016-01-01

    Age-related macular degeneration is the leading cause of adult blindness in the developed world. Thus, major endeavors to understand the risk factors and pathogenesis of this disease have been undertaken. Reticular macular disease is a proposed subtype of age-related macular degeneration correlating histologically with subretinal drusenoid deposits located between the retinal pigment epithelium and the inner segment ellipsoid zone. Reticular lesions are more prevalent in females and in older age groups and are associated with a higher mortality rate. Risk factors for developing age-related macular degeneration include hypertension, smoking, and angina. Several genes related to increased risk for age-related macular degeneration and reticular macular disease are also associated with cardiovascular disease. Better understanding of the clinical and genetic risk factors for age-related macular degeneration and reticular macular disease has led to the hypothesis that these eye diseases are systemic. A systemic origin may help to explain why reticular disease is diagnosed more frequently in females as males suffer cardiovascular mortality at an earlier age, before the age of diagnosis of reticular macular disease and age-related macular degeneration.

  2. Effect of change in macular birefringence imaging protocol on retinal nerve fiber layer thickness parameters using GDx VCC in eyes with macular lesions.

    PubMed

    Dada, Tanuj; Tinwala, Sana I; Dave, Vivek; Agarwal, Anand; Sharma, Reetika; Wadhwani, Meenakshi

    2014-08-01

    This study evaluates the effect of two macular birefringence protocols (bow-tie retardation and irregular macular scan) using GDx VCC on the retinal nerve fiber layer (RNFL) thickness parameters in normal eyes and eyes with macular lesions. In eyes with macular lesions, the standard protocol led to significant overestimation of RNFL thickness which was normalized using the irregular macular pattern protocol. In eyes with normal macula, absolute RNFL thickness values were higher in irregular macular pattern protocols with the difference being statistically significant for all parameters except for inferior average thickness. This has implications for monitoring glaucoma patients who develop macular lesions during the course of their follow-up.

  3. Age-related macular degeneration.

    PubMed

    Lim, Laurence S; Mitchell, Paul; Seddon, Johanna M; Holz, Frank G; Wong, Tien Y

    2012-05-05

    Age-related macular degeneration is a major cause of blindness worldwide. With ageing populations in many countries, more than 20% might have the disorder. Advanced age-related macular degeneration, including neovascular age-related macular degeneration (wet) and geographic atrophy (late dry), is associated with substantial, progressive visual impairment. Major risk factors include cigarette smoking, nutritional factors, cardiovascular diseases, and genetic markers, including genes regulating complement, lipid, angiogenic, and extracellular matrix pathways. Some studies have suggested a declining prevalence of age-related macular degeneration, perhaps due to reduced exposure to modifiable risk factors. Accurate diagnosis combines clinical examination and investigations, including retinal photography, angiography, and optical coherence tomography. Dietary anti-oxidant supplementation slows progression of the disease. Treatment for neovascular age-related macular degeneration incorporates intraocular injections of anti-VEGF agents, occasionally combined with other modalities. Evidence suggests that two commonly used anti-VEGF therapies, ranibizumab and bevacizumab, have similar efficacy, but possible differences in systemic safety are difficult to assess. Future treatments include inhibition of other angiogenic factors, and regenerative and topical therapies.

  4. Macular thickness measurements with frequency domain-OCT for quantification of axonal loss in chronic papilledema from pseudotumor cerebri syndrome

    PubMed Central

    Monteiro, M L R; Afonso, C L

    2014-01-01

    Purpose To evaluate the ability of frequency domain-optical coherence tomography (FD-OCT)-measured macular thickness parameters to differentiate between eyes with resolved chronic papilledema and healthy eyes and to evaluate the correlation between FD-OCT measures and visual field (VF) loss on standard automated perimetry (SAP). Methods Fifty-two eyes from 29 patients suffering from pseudotumor cerebri syndrome (PTC) and 62 eyes from 31 normal controls underwent FD-OCT scanning and ophthalmic evaluation including VF with SAP. All patients had previously been submitted to treatment of PTC and had clinically resolved papilledema and stable VF for at least 6 months before the study. Macular and peripapillary retinal nerve fiber layer (RNFL) thickness measurements were determined for both groups. Comparisons were made using Generalized Estimated Equations. Correlations between FD-OCT and VF measurements were verified. Results In eyes with resolved papilledema, the macular thickness parameters corresponding to the inner and outer superior, temporal, inferior and nasal segments, average macular thickness and most RNFL thickness measurements were significantly reduced when compared with controls. The discrimination ability was similar for macular thickness measurements and RNFL thickness measurements. Both sets of OCT measurements correlated well with VF sensitivity loss. Conclusions Eyes with resolved chronic papilledema show a significant reduction in macular thickness, which is well correlated with the severity of VF loss. Macular thickness measurements can potentially be used to estimate and monitor the amount of ganglion cell loss in eyes with papilledema from patients with PTC. PMID:24406417

  5. Achondroplasia and Macular Coloboma.

    PubMed

    Ahoor, M H; Amizadeh, Y; Sorkhabi, R

    2015-01-01

    Achondroplasia is an autosomal dominant congenital disorder of enchondral ossification. It is clinically characterized by low stature, craniofacial deformity, and vertebral malformation. Associated ophthalmic features include telecanthus, exotropia, angle anomalies, and cone-rod dystrophy. A 24-year-old male presented with decreased vision bilaterally and typical achondroplasia. The best corrected visual acuity was 20/70 in both eyes. Anterior segment examination was normal. Fundus examination revealed a well-demarcated circular paramacular lesion in both eyes. As macular coloboma and achondroplasia are developmental disorders, the funduscopic examination is required in patients with achondroplasia.

  6. A review of ranibizumab clinical trial data in exudative age-related macular degeneration and how to translate it into daily practice.

    PubMed

    Monés, Jordi

    2011-01-01

    The results of randomized controlled clinical trials of ranibizumab for the treatment of age-related macular degeneration established a new standard of care with the prospect of improved vision in many patients. Subsequent trials have explored different strategies to increase response rates and reduce treatment frequency. This review analyzes the key clinical trial data for ranibizumab on the basis of which the author proposes a new treatment regimen with the aim of rationalizing treatment frequency without compromising improvements in vision--the FUSION regimen. This consists of an initiation phase followed by pro re nata (PRN) retreatment combined with fixed injections after a period of disease inactivity of 2-4 months (depending on the time elapsed since the last injection). A randomized clinical trial is recommended for comparing monthly, PRN and the FUSION regimens.

  7. [Initial Clinical Experiences Using Ocriplasmin for the Treatment of Vitreomacular Traction with or without a Macular Hole].

    PubMed

    Lenk, J; Matthé, E; Ventzke, S; Pillunat, L E; Sandner, D

    2017-03-10

    Purpose In vitreomacular traction (VMT), there is abnormal adhesion between the vitreous cortex and the retina, especially in the fovea. Symptoms of VMT include metamorphopsia and a decrease in visual acuity. Since 2013, ocriplasmin (Jetrea®) has been approved for treatment of symptomatic vitreomacular traction with or without macular holes (≤ 400 µm). Methods We retrospectively examined twenty-three eyes of twenty-one patients who underwent intravitreal ocriplasmin treatment for symptomatic vitreomacular traction with or without macular holes. Best corrected visual acuity and central retinal thickness (CRT) were measured in advance and after ocriplasmin treatment. The numbers of resolved vitreomacular traction and closed macular holes were documented. Results Vitreomacular traction was resolved in eight of twenty-three eyes (34.8 %); in fifteen eyes (65.2 %) it was persistent and two of four macular holes were found closed. The average best corrected visual acuity was 0.39 ± 0.25 logMAR at baseline and 0.41 ± 0.24 logMAR at the first follow-up visit after injection (p = 0.613). The average CRT was 453.3 ± 172.7 µm at baseline, with a slight decrease to 412.0 ± 212 µm (p = 0.124). Conclusion Intravitreal injection of ocriplasmin appears is an experimental therapy in patients with symptomatic vitreomacular traction. Patient selection seems to be critically important for the therapeutic outcome, whereas greater age, specific VMT morphology and missing chromatopsia seem to be negative predictors.

  8. Clinical significance of Bacillus species isolated from blood cultures.

    PubMed

    Weber, D J; Saviteer, S M; Rutala, W A; Thomann, C A

    1989-06-01

    To determine the clinical significance of blood isolates of Bacillus, we reviewed all blood cultures obtained at North Carolina Memorial Hospital between 1981 and 1985. Over the five-year study period the number of patients (incidence per 10,000 hospital admissions) from whom Bacillus was isolated increased from 4.97 in 1981 to 12.5 in 1985. The incidence per 1,000 blood cultures also increased from 1.12 in 1981 to 2.33 in 1985. Review of the medical records of 78 of the 95 patients (82%) with positive cultures allowed retrospective classification of five isolates (6.4%) as clinically significant, 33 isolates (42.3%) as possibly significant, and 40 isolates (51.3%) as nonsignificant. Underlying diseases in patients with clinically significant Bacillus bacteremia included burn trauma in two, leukemia in one, carcinoma in one, and gastrointestinal hemorrhage in one. All isolates judged to be clinically significant and the majority of possibly significant isolates were B cereus. We conclude that the isolation of Bacillus species from blood cultures is clinically significant in 5% to 10% of cases, that the incidence of Bacillus bacteremia is increasing, and that burn trauma should be added to the list of conditions known to predispose to clinically significant Bacillus bacteremia.

  9. Macular Degeneration Partnership

    MedlinePlus

    ... Age Related Macular Degeneration) Partnership Listen AMD Month Public Service Announcement To raise awareness of AMD, the Macular Degeneration Partnership (MDP) is distributing a public service announcement (PSA) nationwide. Seen through the eyes of a ...

  10. Children of Divorce: The Question of Clinically Significant Problems.

    ERIC Educational Resources Information Center

    Warren, Nancy J.; And Others

    1986-01-01

    Reports results of a study of a non-clinical sample of children (N=112) from families (N=86) after divorce filing using criteria to assess clinically significant levels of problems in children aged 7-12. Results suggest children may adapt better to divorce than some studies suggest. Children with behavior problems were less likely to have regular…

  11. A clinical study to evaluate the efficacy of intravitreal Anti-VEGF therapy in treating macular edema due to retinal venous occlusions

    PubMed Central

    Kumar, Poninder; Banarji, Ajay; Patyal, Sagarika; Gurunadh, V.S.; Ahluwalia, T.S.; Oli, Avadesh; Moulick, P.S.; Makker, Anuradha

    2013-01-01

    Background A non-randomized, interventional study was carried out various types of retinal venous occlusions with significant macular edema who required an Anti-VEGF injection. Method One hundred and one consecutive patients diagnosed as a case of CRVO/HCRVO/BRVO were enrolled in the study provided they had significant macular edema. Atleast three intra-vitreal injections of Anti-VEGFs were given and both the pre and post injections BCVA and CMT on OCT were observed and analyzed. Results 87 patients (86.14%) showed a significant improvement of vision of atleast two lines on the Snellen's and mean BCVA improved from log MAR +1.084 to log MAR +0.455. CMT on OCT showed reduction in thickness after Anti-VEGF therapy in 99 patients out of 101 and mean CMT decreased from 586.30 μ at baseline to 329.50 μ. Both of these findings were statistically very significant. Conclusions Anti-VEGF therapy had a marked improvement in BCVA along with a dramatic reduction in CMT in the vast majority of RVOs patients with no serious ocular or systemic side effects. PMID:24600120

  12. Update on clinically significant drug interactions in dermatology.

    PubMed

    Barranco, Vincent P

    2006-04-01

    Although there are thousands of drug interactions (DIs) listed in computers and manuals, only about 10% are clinically significant. Equally disturbing is these systems fail to detect up to one third of all dangerous DIs. This update on clinically significant DIs is current through September 2005 and discusses systemic drugs important to dermatologists. In addition, 4 aspects of DIs are discussed that are helpful in replacing rote memory with a step-by-step, logical approach based on scientific evidence.

  13. Macular Degeneration: An Overview.

    ERIC Educational Resources Information Center

    Chalifoux, L. M.

    1991-01-01

    This article presents information on macular degeneration for professionals helping persons with this disease adjust to their visual loss. It covers types of macular degeneration, the etiology of the disease, and its treatment. Also considered are psychosocial problems and other difficulties that persons with age-related macular degeneration face.…

  14. Risk factors of a reduced response to ranibizumab treatment for neovascular age-related macular degeneration – evaluation in a clinical setting

    PubMed Central

    2013-01-01

    Background To identify risk factors for being a “reduced responder” to ranibizumab treatment in a clinical setting in patients with neovascular age-related macular degeneration. Methods This retrospective study included 165 eyes of 165 consecutive patients with choroidal neovascularisation secondary to neovascular, age-related macular degeneration. Eyes were treated with three intravitreal injections of ranibizumab, followed by PRN (pro re nata) dosing thereafter. All patients were reevaluated every four weeks and then followed for six months. Reduced responders were defined as patients with a loss in visual acuity of at least 1 visual acuity line at the last follow-up and/or persistent intraretinal or subretinal fluid or detectable choroidal neovascularisation at the last follow-up, compared to baseline. Results Overall, 58 out of 165 eyes (35.2%) were considered to be reduced responders to treatment at the end of follow-up. The initial CNV size at baseline was correlated with the risk of being a reduced responder at the end of follow-up (p = 0.017). Conclusion We identified the initial lesion size as a predictor for a reduced response to treatment in this study. Patients with a large initial lesion size should be thoroughly informed about the possible poorer response to the intravitreal treatment. PMID:24359591

  15. Dementia Caregiver Intervention Research: In Search of Clinical Significance

    PubMed Central

    Schulz, Richard; O’Brien, Alison; Czaja, Sara; Ory, Marcia; Norris, Rachel; Martire, Lynn M.; Belle, Steven H.; Burgio, Lou; Gitlin, Laura; Coon, David; Burns, Robert; Gallagher-Thompson, Dolores; Stevens, Alan

    2008-01-01

    Purpose We reviewed intervention studies that reported dementia caregiver outcomes published since 1996, including psychosocial interventions for caregivers and environmental and pharmacological interventions for care recipients. Our goal was to focus on issues of clinical significance in caregiver intervention research in order to move the field toward a greater emphasis on achieving reliable and clinically meaningful outcomes. Design and Methods MEDLINE, PsycINFO, and Cumulative Index to Nursing & Allied Health databases from 1996 through 2001 were searched to identify articles and book chapters mapping to two medical subject headings: caregivers and either dementia or Alzheimer’s disease. Articles were evaluated on two dimensions, outcomes in four domains thought to be important to the individual or society and the magnitude of reported effects for these outcomes in order to determine if they were large enough to be clinically meaningful. Results Although many studies have reported small to moderate statistically significant effects on a broad range of outcomes, only a small proportion of these studies achieved clinically meaningful outcomes. Nevertheless, caregiving intervention studies have increasingly shown promise of affecting important public health outcomes in areas such as service utilization, including delayed institutionalization; psychiatric symptomatology, including the successful treatment of major and minor depression; and providing services that are highly valued by caregivers. Implications Assessment of clinical significance in addition to statistical significance is needed in this research area. Specific recommendations on design, measurement, and conceptual issues are made to enhance the clinical significance of future research. PMID:12351794

  16. Optical Coherence Tomography Updates on Clinical and Technical Developments. Age-Related Macular Degeneration: Drusen and Geographic Atrophy

    NASA Astrophysics Data System (ADS)

    Fleckenstein, Monika; Schmitz-Valckenberg, Steffen; Holz, Frank G.

    Age-related macular degeneration (AMD) is a complex disease with both genetic and environmental factors influencing its development. With the advent of high-resolution OCT imaging, the characterization of drusen in AMD has become possible. The in vivo morphologic characteristics imaged with SD-OCT may represent distinct subclasses of drusen variants, may relate closely to ultrastructural drusen elements identified in donor eyes, and may be useful imaging biomarkers for disease severity or risk of progression [Khanifar et al. Ophthalmology 115(11):1883-1890, 2008].

  17. Mass Spectrometric Immunoassays in Characterization of Clinically Significant Proteoforms

    PubMed Central

    Trenchevska, Olgica; Nelson, Randall W.; Nedelkov, Dobrin

    2016-01-01

    Proteins can exist as multiple proteoforms in vivo, as a result of alternative splicing and single-nucleotide polymorphisms (SNPs), as well as posttranslational processing. To address their clinical significance in a context of diagnostic information, proteoforms require a more in-depth analysis. Mass spectrometric immunoassays (MSIA) have been devised for studying structural diversity in human proteins. MSIA enables protein profiling in a simple and high-throughput manner, by combining the selectivity of targeted immunoassays, with the specificity of mass spectrometric detection. MSIA has been used for qualitative and quantitative analysis of single and multiple proteoforms, distinguishing between normal fluctuations and changes related to clinical conditions. This mini review offers an overview of the development and application of mass spectrometric immunoassays for clinical and population proteomics studies. Provided are examples of some recent developments, and also discussed are the trends and challenges in mass spectrometry-based immunoassays for the next-phase of clinical applications. PMID:28248223

  18. Potentially significant versus clinically significant drug interactions: pomegranate juice as a case in point.

    PubMed

    Andrade, Chittaranjan

    2014-04-01

    In vitro and in vivo laboratory data show that pomegranate juice consistently inhibits intestinal CYP2C9 and CYP3A4 enzymes. Pomegranate juice may therefore increase the bioavailability of drugs that are metabolized by these enzymes. However, studies in humans find that pomegranate juice does not increase exposure to either CYP2C9 or CYP3A4 substrates. These contradictory findings suggest that potential drug interactions identified in the laboratory may not necessarily translate into clinically significant drug interactions in humans, and hence that laboratory data are insufficient grounds upon which clinical decisions may be based.

  19. Cognitive Impairment in Individuals with Insomnia: Clinical Significance and Correlates

    PubMed Central

    Fortier-Brochu, Émilie; Morin, Charles M.

    2014-01-01

    Study Objectives: The aims of this study were to (1) investigate the nature of cognitive impairment in individuals with insomnia, (2) document their clinical significance, (3) examine their correlates, and (4) explore differences among individuals with insomnia with and without cognitive complaints. Design: Participants underwent 3 consecutive nights of polysomnography. On the morning following the third night, they completed a battery of questionnaires and neuropsychological tests. Participants: The sample included 25 adults with primary insomnia (mean age: 44.4 ± 11.5 y, 56% women) and 16 controls (mean age: 42.8 ± 12.9 y, 50% women) matched for sex, age, and education. Intervention: N/A. Measurement and Results: Participants completed neuropsychological tests covering attention, memory, working memory, and executive functions, as well as questionnaires assessing the subjective perception of performance, depression, anxiety, fatigue, sleepiness, and hyperarousal. There were significant group differences for the attention and episodic memory domains. Clinically significant deficits were more frequent in the insomnia group. Within the insomnia group, individuals with cognitive complaints exhibited significantly poorer performance on a larger number of neuropsychological variables. All impaired aspects of performance were significantly associated with either subjective or objective sleep continuity, and some were also independently related to sleep microstructure (i.e., relative power for alpha frequencies) or selected psychological variables (i.e., beliefs or arousal). Conclusions: These findings suggest clinically significant alterations in attention and episodic memory in individuals with insomnia. Objective deficits were more pronounced and involved more aspects of performance in a subgroup of individuals with cognitive complaints. These deficits appear associated with sleep continuity, and may also be related to sleep microstructure and dysfunctional beliefs

  20. Macular edema: definition and basic concepts.

    PubMed

    Coscas, Gabriel; Cunha-Vaz, José; Soubrane, Gisèle

    2010-01-01

    Macular edema is the result of an accumulation of fluid in the retinal layers around the fovea. It contributes to vision loss by altering the functional cell relationship in the retina and promoting an inflammatory reparative response. Macular edema may be intracellular or extracellular. Intracellular accumulation of fluid, also called cytotoxic edema, is an alteration of the cellular ionic distribution. Extracellular accumulation of fluid, which is more frequent and clinically more relevant, is directly associated with an alteration of the blood-retinal barrier (BRB). The following parameters are relevant for clinical evaluation of macular edema: extent of the macular edema (i.e., the area that shows increased retinal thickness); distribution of the edema in the macular area (i.e., focal versus diffuse macular edema); central foveal involvement (central area 500 microm); fluorescein leakage (evidence of alteration of the BRB or 'open barrier') and intraretinal cysts; signs of ischemia (broken perifoveolar capillary arcade and/or areas of capillary closure); presence or absence of vitreous traction; increase in retinal thickness and cysts in the retina (inner or outer), and chronicity of the edema (i.e., time elapsed since initial diagnosis and response to therapy). It is essential to establish associations and correlations of all the different images obtained, regardless of whether the same or different modalities are used.

  1. Vascular-targeted photodynamic therapy in the treatment of neovascular age-related macular degeneration: Clinical perspectives.

    PubMed

    Kawczyk-Krupka, A; Bugaj, A M; Potempa, M; Wasilewska, K; Latos, W; Sieroń, A

    2015-06-01

    Vascular targeted photodynamic therapy (VTP), with use of verteporfin as a photosensitizer is one of the few therapies, which has been shown to effectively slow the progression of the "wet" form of age-related macular degeneration (AMD), and even to stabilize visual acuity over many years. Although, due to considerable advance of AMD treatment, it is currently not recommended in monotherapy of AMD, however, its combination with steroids and anti-angiogenic biologic drugs may reveal high therapeutic potential in the treatment of neovascular AMD. The future of VTP as a method of AMD treatment is development of new selective and targeted photosensitizer and combination of this method with other therapeutic strategies targeting cellular structures or pathways involved in AMD progression.

  2. [Pharmacological therapy of age-related macular degeneration based on etiopathogenesis].

    PubMed

    Fischer, Tamás

    2015-11-15

    It is of great therapeutic significance that disordered function of the vascular endothelium which supply the affected ocular structures plays a major role in the pathogenesis and development of age-related macular degeneration. Chronic inflammation is closely linked to diseases associated with endothelial dysfunction, and age-related macular degeneration is accompanied by a general inflammatory response. According to current concept, age-related macular degeneration is a local manifestation of systemic vascular disease. This recognition could have therapeutic implications because restoration of endothelial dysfunction can restabilize the condition of chronic vascular disease including age-related macular degeneration as well. Restoration of endothelial dysfunction by pharmaacological or non pharmacological interventions may prevent the development or improve endothelial dysfunction, which result in prevention or improvement of age related macular degeneration as well. Medicines including inhibitors of the renin-angiotensin system (converting enzyme inhibitors, angiotensin-receptor blockers and renin inhibitors), statins, acetylsalicylic acid, trimetazidin, third generation beta-blockers, peroxisome proliferator-activated receptor gamma agonists, folate, vitamin D, melatonin, advanced glycation end-product crosslink breaker alagebrium, endothelin-receptor antagonist bosentan, coenzyme Q10; "causal" antioxidant vitamins, N-acetyl-cysteine, resveratrol, L-arginine, serotonin receptor agonists, tumor necrosis factor-alpha blockers, specific inhibitor of the complement alternative pathway, curcumin and doxycyclin all have beneficial effects on endothelial dysfunction. Restoration of endothelial dysfunction can restabilize chronic vascular disease including age-related macular degeneration as well. Considering that the human vascular system is consubstantial, medicines listed above should be given to patients (1) who have no macular degeneration but have risk factors

  3. Emerging Bacterial Infection: Identification and Clinical Significance of Kocuria Species

    PubMed Central

    Palange, Padmavali; Vaish, Ritu; Bhatti, Adnan Bashir; Kale, Vinod; Kandi, Maheshwar Reddy; Bhoomagiri, Mohan Rao

    2016-01-01

    Recently there have been reports of gram-positive cocci which are morphologically similar to both Staphylococci and the Micrococci. These bacteria have been identified as Kocuria species with the help of automated identification system and other molecular methods including 16S rRNA (ribosomal ribonucleic acid) evaluation. Kocuria belongs to the family Micrococcaceae which also includes Staphylococcus species and Micrococcus species. Isolation and clinical significance of these bacteria from human specimens warrant great caution as it does not necessarily confirm infection due to their ubiquitous presence, and as a normal flora of skin and mucous membranes in human and animals. Most clinical microbiology laboratories ignore such bacteria as laboratory and specimen contaminants. With increasing reports of infections associated with these bacteria, it is now important for clinical microbiologists to identify and enumerate the virulence and antibiotic susceptibility patterns of such bacteria and assist clinicians in improving the patient care and management. We review the occurrence and clinical significance of Kocuria species. PMID:27630804

  4. Complications of Macular Peeling

    PubMed Central

    Asencio-Duran, Mónica; Manzano-Muñoz, Beatriz; Vallejo-García, José Luis; García-Martínez, Jesús

    2015-01-01

    Macular peeling refers to the surgical technique for the removal of preretinal tissue or the internal limiting membrane (ILM) in the macula for several retinal disorders, ranging from epiretinal membranes (primary or secondary to diabetic retinopathy, retinal detachment…) to full-thickness macular holes, macular edema, foveal retinoschisis, and others. The technique has evolved in the last two decades, and the different instrumentations and adjuncts have progressively advanced turning into a safer, easier, and more useful tool for the vitreoretinal surgeon. Here, we describe the main milestones of macular peeling, drawing attention to its associated complications. PMID:26425351

  5. Accurate coding in sepsis: clinical significance and financial implications.

    PubMed

    Chin, Y T; Scattergood, N; Thornber, M; Thomas, S

    2016-09-01

    Sepsis is a major healthcare problem and leading cause of death worldwide. UK hospital mortality statistics and payments for patient episodes of care are calculated on clinical coding data. The accuracy of these data depends on the quality of coding. This study aimed to investigate whether patients with significant bacteraemia are coded for sepsis and to estimate the financial costs of miscoding. Of 54 patients over a one-month period with a significant bacteraemia, only 19% had been coded for sepsis. This is likely to lead to falsely high calculated hospital mortality. Furthermore, this resulted in an underpayment of £21,000 for one month alone.

  6. Compact single-channel Raman detector for macular pigments

    NASA Astrophysics Data System (ADS)

    Ermakov, Igor V.; Ermakova, Maia R.; Gellermann, Werner

    2004-07-01

    Raman detection of macular pigments (MP) holds promise as a novel noninvasive technology for the quantification of lutein and zeaxanthin carotenoids, which are thought to prevent or delay the onset of age-related macular degeneration. Using resonant excitation in the visible, we measure the Raman signals that originate from the double-bond stretch vibrations of the p-conjugated carotenoid molecule's carbon backbone. In this paper we describe the construction and performance of a new, compact, and low-cost MP Raman instrument using dielectric, angle-tuned band-pass filters for wavelength selection and single-channel photo-multiplier detection of carotenoid Raman responses. MP concentration measurements are fast and accurate, as seen in experiments with model eyes and living human eyes. The ease and rapidity of Raman MP measurements, the relative simplicity of the instrumentation, the high accuracy of the measurements, and the lack of significant systematic errors should make this technology useful for widespread clinical research.

  7. Prevalence and clinical significance of rare antinuclear antibody patterns.

    PubMed

    Vermeersch, Pieter; Bossuyt, Xavier

    2013-08-01

    While some of the more frequent antinuclear (auto)antibodies (ANA) patterns such as homogenous nuclear staining have been extensively studied, the prevalence and clinical significance of rare antinuclear antibody patterns are not well understood. For the purpose of this review, we defined rare patterns as patterns occurring in less than 1% of patients that test positive on indirect immunofluorescence. The prevalence of different ANA patterns was determined in 68,128 consecutive patients who attended the outpatient clinic or were hospitalized at the University Hospitals Leuven over a 14-year period (1998-2011). To avoid bias, we only included the first sample for each patient and patients who tested positive in the period 1980-1997 were excluded. There were 9268 patients who tested positive for ANA. With the exception of the clinical association of anti-multiple nuclear dots (at higher titers) and anti-nuclear envelope autoantibodies with autoimmune liver disease, there was no good clinical association of rare ANA patterns with the diagnosis of auto-immune disorders. The most important non-autoimmune cause of rare ANA patterns was carcinoma, particularly in patients with rare cell-cycle related ANAs.

  8. Macular pigment and lutein supplementation in choroideremia.

    PubMed

    Duncan, Jacque L; Aleman, Tomas S; Gardner, Leigh M; De Castro, Elaine; Marks, Daniel A; Emmons, Jessica M; Bieber, Michelle L; Steinberg, Janet D; Bennett, Jean; Stone, Edwin M; MacDonald, Ian M; Cideciyan, Artur V; Maguire, Maureen G; Jacobson, Samuel G

    2002-03-01

    Choroideremia is an incurable X-linked retinal degeneration caused by mutations in the gene encoding Rab escort protein-1. A group of clinically defined and genotyped patients were studied to determine: (1) the degree of rod and cone dysfunction and structural abnormality in the central retina and the level of macular pigment; and (2) the response of macular pigment and foveal vision to a 6 month trial of supplementation with oral lutein (at 20 mg per day). Rod and cone-mediated function was measured with dark-adapted static perimetry; in vivo retinal structure was determined with optical coherence tomography; and macular pigment optical density was measured with heterochromatic flicker photometry. In this cohort of patients (ages 15-65 years), both rod- and cone-mediated central function declined with age as did central retinal thickness. Macular pigment levels did not differ between patients and male control subjects. Supplementation of oral lutein in a subset of patients led to an increase in serum lutein and macular pigment levels; absolute foveal sensitivity did not change. It is concluded that macular pigment density can be augmented by oral intake of lutein in patients with choroideremia. There was no short-term change in the central vision of the patients on the supplement, but long-term influences of lutein supplementation on disease natural history warrant further study.

  9. Clinical significance of TIPE expression in gastric carcinoma

    PubMed Central

    Hu, Ruyi; Qiu, Xingfeng; Hong, Shifu; Meng, Luxi; Hong, Xinya; Qiu, Jinhua; Yang, Jingjing; Zhuang, Guohong; Liu, Zhongchen

    2016-01-01

    Background TNFAIP8, also known as TIPE, is a suppressor of apoptosis. High expression of both TIPE mRNA and protein has been detected in various cancer cell lines and clinical specimens compared to healthy tissues. Many reports have shown that there is a strong correlation between TIPE overexpression and cancer progression and poor prognosis in human solid cancers. Methods To illustrate the functional and clinical significance of TIPE in gastric cancer, we used reverse transcription polymerase chain reaction, quantitative real-time polymerase chain reaction, and immunohistochemistry to measure TIPE expression in clinical gastric specimens. Then, TIPE expression was knocked down by using shRNA and anti-DR5ScFv, to examine different expressions of TIPE in BGC823 cell lines, while cell proliferation and apoptosis were induced. Results We found that there was a strong correlation between TIPE expression and TNM stage (P=0.044), tumor depth (P=0.016), lymph node metastasis (P=0.026), and distant metastasis (P=0.045). No significant correlation was found between TIPE expression with the patients’ age (P=0.062) or sex (P=0.459). Anti-DR5ScFv induced TIPE depletion both in vitro and in vivo and resulted in apoptosis and suppression of proliferation. Conclusion Our results suggested that TIPE expression was associated with gastric cancer progression, and most importantly, suppressing TIPE expression might be an effective therapeutic strategy. PMID:27524904

  10. Worksite stress management training: moderated effects and clinical significance.

    PubMed

    Flaxman, Paul E; Bond, Frank W

    2010-10-01

    Psychologically healthy participants may dilute the observed effects of worksite stress management training (SMT) programs, therefore hiding the true effectiveness of these interventions for more distressed workers. To examine this issue, 311 local government employees were randomly assigned to SMT based on acceptance and commitment therapy (SMT, n = 177) or to a waitlist control group (n = 134). The SMT program consisted of three half-day training sessions, and imparted a mixture of mindfulness and values-based action skills. Across a 6-month assessment period, SMT resulted in a significant reduction in employee distress. As predicted, the impact of SMT was significantly moderated by baseline distress, such that meaningful effects were found only among a subgroup of initially distressed workers. Furthermore, a majority (69%) of these initially distressed SMT participants improved to a clinically significant degree. The study highlights the importance of accounting for sample heterogeneity when evaluating and classifying worksite SMT programs.

  11. [Circular RNA in human disease and their potential clinic significance].

    PubMed

    Chen, Yonghua; Li, Cheng; Tan, Chunlu; Mai, Gang; Liu, Xubao

    2017-02-10

    Circular RNAs (circ RNAs) are a novel type of RNA that, unlike linear RNAs, form a covalently closed continuous loop and are highly represented in the eukaryotic transcriptome. They share a stable structure, high expression and often exhibit tissue/developmental-stage-specific expression. Emerging evidence indicates that circRNAs might play important roles in human disease, such as cancer, neurological disorders and atherosclerotic vascular disease risk. The huge potentials of circRNAs are recently being discovered from the laboratory to the clinic. CircRNAs might be developed as a potential novel and stable biomarker and potential drugs used in disease diagnosis and treatment. Here, we review the current understanding of the roles of circRNAs in human disease and their potential clinic significance in disease.

  12. Teardrop shadow of the pelvis: anatomy and clinical significance

    SciTech Connect

    Bowerman, J.W.; Sena, J.M.; Chang, R.

    1982-06-01

    The teardrop shadow of the pelvis is poorly understood and as a result its clinical significance is not appreciated. The structure responsible for this shadow was pinpointed by removing sections from the hemipelvis of an anatomic specimen with an electric saw. This structure is located in the anteroinferior portion of the acetabular fossa at the acetabular notch and consists of cortical and medullary bone contributed primarily from the ischium with a much smaller contribution from the superior pubic ramus. The normal and abnormal appearances of the teardrop shadow of the acetabulum of three patients were demonstrated on both plain radiographs and computed tomographic (CT) scans.

  13. [The significance of mammographic symptoms in clinically occult findings].

    PubMed

    de Waal, J C; Steil, B; Baltzer, J; Vaillant, W; Zander, J

    1987-10-01

    The significance of various radiographic signs in 183 patients with clinically occult breast disease is described. 30.6% had a carcinoma of the breast or a carcinoma in situ. The radiological features have varying predictive values and there is variation in the incidence of lymph node metastases. It is considered useful to classify the radiological appearances under the headings of round foci, star-shaped opacities, diffuse opacities, opacities with calcification and groups of micro-calcification. Despite the early diagnosis, 24% of patients already had lymph node metastases.

  14. The role of proteases and inflammatory molecules in triggering neovascular age-related macular degeneration: basic science to clinical relevance.

    PubMed

    Balasubramanian, Sivaraman A; Krishna Kumar, Kaavya; Baird, Paul N

    2014-09-01

    Age-related macular degeneration (AMD) causes severe vision impairment in aged individuals. The health impact and cost of the disease will dramatically increase over the years, with the increase in the aging population. Currently, antivascular endothelial growth factor agents are routinely used for managing late-stage AMD, and recent data have shown that up to 15%-33% of patients do not respond to this treatment. Henceforth, there is a need to develop better treatment options. One avenue is to investigate the role proteases and inflammatory molecules might have in regulating and being regulated by vascular endothelial growth factor. Moreover, emerging data indicate that proteases and inflammatory molecules might be critical in the development and progression of AMD. This article reviews recent literature that investigates proteases and inflammatory molecules involved in the development of AMD. Gaining insights into the proteolytic and inflammatory pathways associated with the pathophysiology of AMD could enable the development of additional or alternative drug strategies for the treatment of AMD.

  15. Mechanism and clinical significance of prostaglandin-induced iris pigmentation.

    PubMed

    Stjernschantz, Johan W; Albert, Daniel M; Hu, Dan-Ning; Drago, Filippo; Wistrand, Per J

    2002-08-01

    The new glaucoma drugs latanoprost, isopropyl unoprostone, travoprost, and bimatoprost cause increased pigmentation of the iris in some patients. The purpose of the present article is to survey the available preclinical and clinical data on prostaglandin-induced iris pigmentation and to assess the phenomenon from a clinical perspective. Most of the data have been obtained with latanoprost, and it appears that there is a predisposition to latanoprost-induced iris pigmentation in individuals with hazel or heterochromic eye color. As latanoprost and travoprost are selective agonists for the prostaglandin F(2alpha) receptor, it is likely that the phenomenon is mediated by this receptor. Several studies indicate that latanoprost stimulates melanogenesis in iridial melanocytes, and transcription of the tyrosinase gene is upregulated. The safety aspects of latanoprost-induced iris pigmentation have been addressed in histopathologic studies, and no evidence of harmful consequences of the side effect has been found. Although a final assessment of the clinical significance of prostaglandin-induced iris pigmentation currently is impossible to make, it appears that the only clear-cut disadvantage is a potential heterochromia between the eyes in unilaterally treated patients because the heterochromia is likely to be permanent, or very slowly reversible.

  16. The Prostate Health Index Selectively Identifies Clinically Significant Prostate Cancer

    PubMed Central

    Loeb, Stacy; Sanda, Martin G.; Broyles, Dennis L.; Shin, Sanghyuk S.; Bangma, Chris H.; Wei, John T.; Partin, Alan W.; Klee, George G.; Slawin, Kevin M.; Marks, Leonard S.; van Schaik, Ron H. N.; Chan, Daniel W.; Sokoll, Lori J.; Cruz, Amabelle B.; Mizrahi, Isaac A.; Catalona, William J.

    2015-01-01

    Purpose The Prostate Health Index (phi) is a new test combining total, free and [-2]proPSA into a single score. It was recently approved by the FDA and is now commercially available in the U.S., Europe and Australia. We investigate whether phi improves specificity for detecting clinically significant prostate cancer and can help reduce prostate cancer over diagnosis. Materials and Methods From a multicenter prospective trial we identified 658 men age 50 years or older with prostate specific antigen 4 to 10 ng/ml and normal digital rectal examination who underwent prostate biopsy. In this population we compared the performance of prostate specific antigen, % free prostate specific antigen, [-2]proPSA and phi to predict biopsy results and, specifically, the presence of clinically significant prostate cancer using multiple criteria. Results The Prostate Health Index was significantly higher in men with Gleason 7 or greater and “Epstein significant” cancer. On receiver operating characteristic analysis phi had the highest AUC for overall cancer (AUCs phi 0.708, percent free prostate specific antigen 0.648, [-2]proPSA 0.550 and prostate specific antigen 0.516), Gleason 7 or greater (AUCs phi 0.707, percent free prostate specific antigen 0.661, [-2]proPSA 0.558, prostate specific antigen 0.551) and significant cancer (AUCs phi 0.698, percent free prostate specific antigen 0.654, [-2]proPSA 0.550, prostate specific antigen 0.549). At the 90% sensitivity cut point for phi (a score less than 28.6) 30.1% of patients could have been spared an unnecessary biopsy for benign disease or insignificant prostate cancer compared to 21.7% using percent free prostate specific antigen. Conclusions The new phi test outperforms its individual components of total, free and [-2]proPSA for the identification of clinically significant prostate cancer. Phi may be useful as part of a multivariable approach to reduce prostate biopsies and over diagnosis. PMID:25463993

  17. [Genomics of lung adenocarcinoma: pathogenetic significance and clinical applications.

    PubMed

    Palmirotta, Raffaele; Acquafredda, Silvana; Argentiero, Antonella; Carella, Claudia; Lanotte, Laura; Pappagallo, Nicla; Quaresmini, Davide; Silvestris, Franco

    2016-12-01

    Diagnostic and therapeutic approaches to non small cell lung cancer (NSCLC), especially adenocarcinoma, have recently undergone dramatic evolution according to the tremendous amount of molecular data collected on this cancer. In fact, the application of oncogenomics has identified novel molecular subtypes of NSCLC and led the way to diagnostic criteria based on the expression of specific genetic alterations that can provide prognostic and specific indications to the molecular targeted therapies. In NSCLC, several genes show "driver" molecular alterations that confer oncogenic potential to progenitor cells through the enrollment of metabolic pathways critical for cell proliferation and tumor development. On the other hand, clinical management of NSCLC with small molecules has undoubtedly provided optimistic results with both a significant increase in overall survival and reduction in therapy-related toxicity including relative complications. Thus, pharmacogenomics, as the newest tool for using the targeted therapy represents the most innovative approach for treatment of this cancer once the molecular aberrations are identified. In particular, the relative mutational status of several driver genes including EGFR, ALK, ROS1 and others, is directly correlated to a better response to thyrosin-kinase inhibitors. Furthermore, other therapeutic strategies with inhibitors of angiogenic receptors, PARP, histone-deacetylase, PI3K and HSP90, are intensively studied in pre-clinical models as well as in clinical trials for a potential adoption in clinical practice. The introduction of more advanced techniques for molecular profiling also allows to identify pathogenic variants of many other genes involved in the progression of lung adenocarcinoma with the aim to develop novel molecular targets for pharmacological research. In this review, we will revisit the current applications of oncogenomics in the diagnosis and treatment of this tumor.

  18. Clinical significance and prevalence of Blastocystis hominis in Van, Turkey

    PubMed Central

    Beyhan, Yunus E.; Yilmaz, Hasan; Cengiz, Zeynep T.; Ekici, Abdurrahman

    2015-01-01

    Objectives: To determine the associated clinical symptoms and prevalence of Blastocystis hominis (B. hominis). Methods: Stool samples of 50,185 patients (26,784 males and 23,401 females) who were received at the Parasitology Laboratory of Yuzuncu Yil University Faculty of Medicine, Van, Turkey in the last 5 years were inspected microscopically using saline and iodine-stained wet-mount preparations. Age, gender, and symptoms of patients were recorded and their significance was evaluated. Results: The prevalence of B. hominis in the total sample was 0.54% (275/50185). Out of 275 infected patients, 143 (52%) were males, and 132 (48%) were female (χ2=0.884; p=0.348). The distribution of B. hominis infection was high in 7-13 aged children (34.9%) (χ2=306.8; p=0.001). Blastocystis was higher among symptomatic patients (70.2%) compared with asymptomatic patients (29.8%) (χ2=107.13; p=0.001). The most frequent clinical symptoms associated with the disease were abdominal pain (27.3%) and diarrhea (19.6%) followed by anorexia, fever, saliva, anal itching, and nausea. Conclusion: Blastocystis hominis is considered a causative agent of human disease in patients with recurrent symptoms. Due to the significant risk for zoonotic transmission, molecular techniques must be used to determine the route and source of infection. PMID:26318472

  19. The clinical significance of keratinized gingiva around dental implants.

    PubMed

    Greenstein, Gary; Cavallaro, John

    2011-10-01

    Whether or not keratinized tissue is needed around dental implants to maintain peri-implant health is a controversial subject. To clarify this issue a search was conducted for clinical trials that appraised the significance ofkeratinized gingiva (KG) around teeth and dental implants. A critical assessment of the data revealed that the literature is replete with studies that contradict one another with respect to the need for KG as it relates to survivability of implants, gingival response to plaque, inflammation, probing depths, recession, and loss of bone. When groups of patients with and without KG were compared with respect to various clinical parameters, a statistically significant better result in the presence of KG could be interpreted to indicate that having KG is advantageous. However, quantitative differences between groups with and without KG were usually very small. Overall, the data was interpreted to indicate that some patients may need augmentation of keratinized tissue to maintain peri-implant health. Ultimately, the decision to augment KG is a judgment call that needs to be made by the treating clinician, because there are not enough data to facilitate development of definitive guidelines relevant to this subject. Apparently, the need for KG is patient specific, and at present there is no method to reliably predict who would benefit from tissue augmentation.

  20. Additional branches of celiac trunk and its clinical significance.

    PubMed

    Nayak, S R; Prabhu, Latha V; Krishnamurthy, A; Ganesh Kumar, C; Ramanathan, Lakshmi A; Acharya, Abhijith; Prasad Sinha, Abhishek

    2008-01-01

    The anatomical variations of the abdominal arteries are important due to its clinical significance. Various types of vascular anomalies are frequently found in human abdominal viscera, during cadaveric dissection and diagnostic radiological imaging. The present report describes a variation in the celiac trunk as found during routine dissection in a 59-year-old male cadaver. The celiac trunk (CT) was unusually lengthy and took origin from the left antero-lateral surface of the abdominal aorta. Altogether, there were five branches, including three classic branches of CT. The left phrenic artery (LPA) was the first branch of the CT. The remaining four branches were left gastric artery (LGA), splenic artery (SA), common hepatic artery (CHA) and gastroduodenal artery (GDA). There was an arterial loop between the posterior branches of the superior pancreatico-duodenal artery (SPDA), arising from the GDA, and the posterior branch of the inferior pancreatico-duodenal artery (IPDA), arising from the superior mesenteric artery (SMA). The arterial loop formed by the above arteries, supplied the head of the pancreas and duodeno-jejunal flexure. The embryological and clinical significance of above variations has been described.

  1. Clinical and Biological Significance of Tissue Transglutaminase in Ovarian Carcinoma

    PubMed Central

    Hwang, Jee Young; Mangala, Lingegowda S.; Fok, Jansina Y.; Lin, Yvonne G.; Merritt, William M.; Spannuth, Whitney A.; Nick, Alpa M.; Fiterman, Derek J.; Vivas-Mejia, Pablo E.; Deavers, Michael T.; Coleman, Robert L.; Lopez-Berestein, Gabriel; Mehta, Kapil; Sood, Anil K.

    2008-01-01

    Tissue type transglutaminase (TG2) is a unique multifunctional protein that plays a role in many steps in the cancer metastatic cascade. Here, we examined the clinical (n = 93 epithelial ovarian cancers) and biological (in vitro adhesion, invasion, and survival and in vivo therapeutic targeting) significance of TG2 in ovarian cancer. The overexpression of TG2 was associated with significantly worse overall patient survival in both univariate and multivariate analyses. Transfection of TG2 into the SKOV3ip1 cells promoted attachment and spreading on fibronectin-coated surfaces and increased the in vitro invasive potential of these cells. Conversely, TG2 silencing with siRNA of HeyA8 cells significantly decreased the invasive potential of the cells, and also increased docetaxel-induced cell death. In vivo therapy experiments using chemotherapy-sensitive (HeyA8) and resistant (HeyA8-MDR, RMG2) models demonstrated significant anti-tumor activity both with TG2 siRNA-DOPC alone and in combination with docetaxel chemotherapy. This anti-tumor activity was related to decreased proliferation, angiogenesis and increased tumor cell apoptosis in vivo. Taken together, these findings indicate that TG2 overexpression is an adverse prognostic factor in ovarian carcinoma and TG2 targeting may be an attractive therapeutic approach. PMID:18632639

  2. The questioned p value: clinical, practical and statistical significance.

    PubMed

    Jiménez-Paneque, Rosa

    2016-09-09

    The use of p-value and statistical significance have been questioned since the early 80s in the last century until today. Much has been discussed about it in the field of statistics and its applications, especially in Epidemiology and Public Health. As a matter of fact, the p-value and its equivalent, statistical significance, are difficult concepts to grasp for the many health professionals some way involved in research applied to their work areas. However, its meaning should be clear in intuitive terms although it is based on theoretical concepts of the field of Statistics. This paper attempts to present the p-value as a concept that applies to everyday life and therefore intuitively simple but whose proper use cannot be separated from theoretical and methodological elements of inherent complexity. The reasons behind the criticism received by the p-value and its isolated use are intuitively explained, mainly the need to demarcate statistical significance from clinical significance and some of the recommended remedies for these problems are approached as well. It finally refers to the current trend to vindicate the p-value appealing to the convenience of its use in certain situations and the recent statement of the American Statistical Association in this regard.

  3. HMGA2 Expression in Renal Carcinoma and its Clinical Significance

    PubMed Central

    Liu, Ying; Fu, Qi-Zhong; Pu, Lin; Meng, Qing-Guo; Liu, Xian-Feng; Dong, Sheng-Fang; Yang, Jian-Xun; Lv, Guang-Yao

    2015-01-01

    Summary Background The objective of this study is to detect HMGA2 expression in renal carcinoma to explore its relationship with clinicopathology and its significance in prognosis. Methods Expressions of HMGA2 mRNA and protein were detected in 50 renal carcinoma specimens, 50 corresponding adjacent normal kidney tissue samples and 40 renal benign tumour specimens via reverse transcription polymerase chain reaction and immunohistochemical assay. Expression analysis was performed along with clinical data analysis. Results The relative expression levels of HMGA2 mRNA in renal carcinoma, renal benign tumour tissues and adjacent normal renal tissues were 0.84±0.23, 0.19±0.06 and 0.08±0.04, respectively. HMGA2 protein positive rates were 68.0%, 7.5% and 2.0%, with a significant difference (P<0.05). HMGA2 expression was not significantly correlated with gender, age, tumour size and histological type (P>0.05), but was significantly correlated with TNM stages and lymph node metastasis (P<0.05). Conclusions The expressions of HMGA2 gene and protein in renal carcinoma were closely correlated with tumour formation, progression and metastasis. HMGA2 may become a powerful new pathological marker and prognostic factor for renal carcinoma. PMID:28356845

  4. [Age-related macular degeneration].

    PubMed

    Budzinskaia, M V

    2014-01-01

    The review provides an update on the pathogenesis and new treatment modalities for neovascular age-related macular degeneration (AMD). The impact of polymorphism in particular genes, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), and serine peptidase (HTRA1), on AMD development is discussed. Clinical presentations of different forms of exudative AMD, that is classic, occult, or more often mixed choroidal neovascularization, retinal angiomatous proliferation, and choroidal polypoidal vasculopathy, are described. Particular attention is paid to the results of recent clinical trials and safety issues around the therapy.

  5. Clinical and histological evaluation of large macular hole surgery using the inverted internal limiting membrane flap technique

    PubMed Central

    Kase, Satoru; Saito, Wataru; Mori, Shohei; Saito, Michiyuki; Ando, Ryo; Dong, Zhenyu; Suzuki, Tomohiro; Noda, Kousuke; Ishida, Susumu

    2017-01-01

    Purpose The aims of this study were to analyze optical coherence tomography (OCT) imaging of large macular holes (MHs) treated with inverted internal limiting membrane (ILM) flap technique and to perform a histological examination of an ILM-like membrane tissue obtained during vitrectomy. Patients and methods This is a retrospective observational case study. Nine patients, comprising of five males and four females, showing large and myopic MHs, underwent pars plana vitrectomy (PPV) with inverted ILM flap technique assisted by brilliant blue G (BBG) staining. Ophthalmological findings including visual acuity and OCT were investigated based on medical records. Formalin-fixed paraffin-embedded tissue section of an ILM-like membrane was submitted for immunohistochemistry with glial fibrillary acidic protein (GFAP). Results ILM was clearly stained with BBG in eight patients, whereas the ILM in one case revealed no staining with BBG during PPV. Visual acuities improved to >0.2 LogMAR in six patients. The complete closure of MH following PPV with inverted ILM technique was eventually achieved in all patients determined by OCT imaging (100%). Only one patient showed recovery of ellipsoid zone and interdigitation zone following the surgery. Elongation of outer nuclear layer was noted in three eyes. The ILM-like membrane not stained with BBG histologically revealed an amorphous structure admixed with GFAP-positive mononuclear cell infiltration. Conclusion PPV with inverted ILM flap technique achieved 100% closure rates with favorable configuration at an initial surgery in large MHs. Our histopathological data also suggest that even BBG staining-negative membrane may be a useful material for autologous transplantation to the hole. PMID:28031697

  6. Clinical significance of plasma metastin level in pancreatic cancer patients.

    PubMed

    Katagiri, Fumihiko; Nagai, Kazuyuki; Kida, Atsushi; Tomita, Kenji; Oishi, Shinya; Takeyama, Masaharu; Doi, Ryuichiro; Fujii, Nobutaka

    2009-03-01

    Metastin, which is a 54-residue peptide coded by KiSS-1 gene, is an endogenous ligand to a G-protein-coupled receptor GPR54. Metastin suppresses a malignant tumor to metastasize and regulates secretion of gonadotropine releasing hormone. Physiological action of metastin has been focused on in oncology. It is reported that less KiSS-1 gene and more hOT7T175 gene which codes GPR54 are expressed in pancreatic cancers than in normal pancreatic tissues; however, there is no study that investigates the relationship between clinicopathological characteristics and plasma metastin concentration in pancreatic cancer patients. The purpose of this study was to investigate the relationship between plasma metastin-like immunoreactive substance (LI) levels and clinical characteristics in pancreatic cancer patients. Thirty-three patients with pathologically confirmed pancreatic cancer before or just after treatments and 24 healthy volunteers were included in the study. Patients were grouped according to the International Union Against Cancer TNM classification. Plasma metastin-LI was measured by enzyme immunoassay. The plasma metastin-LI levels of cancer patients were significantly higher when compared with healthy volunteers. Significant relationship was not found between the plasma metastin-LI levels and the clinicopathological factors such as tumor size, invasion, lymph node metastasis and distant metastasis. The plasma metastin levels may be a significant biomarker to predict the presence of pancreatic cancer and could be used in pancreatic cancer screening.

  7. Clinical significance of computed tomography assessment for third molar surgery

    PubMed Central

    Nakamori, Kenji; Tomihara, Kei; Noguchi, Makoto

    2014-01-01

    Surgical extraction of the third molar is the most commonly performed surgical procedure in the clinical practice of oral surgery. Third molar surgery is warranted when there is inadequate space for eruption, malpositioning, or risk for cyst or odontogenic tumor formation. Preoperative assessment should include a detailed morphologic analysis of the third molar and its relationship to adjacent structures and surrounding tissues. Due to developments in medical engineering technology, computed tomography (CT) now plays a critical role in providing the clear images required for adequate assessment prior to third molar surgery. Removal of the maxillary third molar is associated with a risk for maxillary sinus perforation, whereas removal of the mandibular third molar can put patients at risk for a neurosensory deficit from damage to the lingual nerve or inferior alveolar nerve. Multiple factors, including demographic, anatomic, and treatment-related factors, influence the incidence of nerve injury during or following removal of the third molar. CT assessment of the third molar prior to surgery can identify some of these risk factors, such as the absence of cortication between the mandibular third molar and the inferior alveolar canal, prior to surgery to reduce the risk for nerve damage. This topic highlight presents an overview of the clinical significance of CT assessment in third molar surgery. PMID:25071882

  8. Effect of topical isopropyl unoprostone on macular atrophy progression in eyes with exudative age-related macular degeneration

    PubMed Central

    Shiragami, Chieko; Miyake, Masahiro; Fujiwara, Atsushi; Morizane, Yuki; Tsujikawa, Akitaka; Yamashita, Ayana; Shiraga, Fumio

    2017-01-01

    Abstract Background: To evaluate the efficacy and safety of topical isopropyl unoprostone (IU) in treating macular atrophy in age-related macular degeneration (AMD) patients. Methods: Fifty-two AMD patients with macular atrophy were included and randomly assigned (1:1) to the treatment (topical 0.15% IU) or placebo group. Subjects used study eye drops 3 times a day for 54 weeks. The macular atrophy was documented on fundus autofluorescence photographs and measured using RegionFinder. The enlargement rate of macular atrophy and the changes in visual acuity were examined statistically between baseline and 54 weeks. Results: Forty-eight subjects were included in the analyses because 4 subjects withdrew from the study. The differences between the IU and placebo groups in mean and median area of macular atrophy were not statistically significant at baseline. The baseline median lesion size of macular atrophy was 2.33 mm2 in the IU group and 1.63 mm2 in the placebo group (P = 0.51). The intergroup difference in the enlargement ratio of macular atrophy (21 ± 15% in the IU group and 111 ± 96% in the placebo group) was statistically significant (P < 0.001). Additionally, visual acuity tended to improve over baseline in the IU group. No serious adverse events were observed. Conclusions: Topical IU therapy is safe and effective for treating macular atrophy in AMD patients. PMID:28328847

  9. Clinical significance of Aeromonas species isolated from patients with diarrhea.

    PubMed

    Moyer, N P

    1987-11-01

    A total of 248 strains of Aeromonas spp. were isolated from 3,334 human fecal specimens submitted to a state public health laboratory over a 2-year period to be cultured for enteric pathogens. Cary-Blair transport medium, blood ampicillin agar, and alkaline peptone water enrichment provided optimal recovery of Aeromonas spp. A questionnaire requesting clinical and epidemiological information was sent to physicians, who submitted stool samples for testing, with each laboratory report for 107 consecutive stool isolates of Aeromonas spp. The 56 questionnaires which were completed and returned were analyzed to determine the seasonal distribution of illness and the age and sex distribution of patients; characteristic symptoms; and predisposing factors for gastrointestinal disease caused by Aeromonas spp. It was concluded that some A. hydrophila, A. sobria, and A. caviae strains are capable of causing diarrhea and that antibiotic therapy and the drinking of untreated water are significant risk factors for susceptible hosts.

  10. Biomarkers of Metabolic Syndrome: Biochemical Background and Clinical Significance.

    PubMed

    Robberecht, Harry; Hermans, Nina

    2016-03-01

    Biomarkers of the metabolic syndrome are divided into four subgroups. Although dividing them in groups has some limitations, it can be used to draw some conclusions. In a first part, the dyslipidemias and markers of oxidative stress are discussed, while inflammatory markers and cardiometabolic biomarkers are reviewed in a second part. For most of them, the biochemical background and clinical significance are discussed, although here also a well-cut separation cannot always be made. Altered levels cannot always be claimed as the cause, risk, or consequence of the syndrome. Several factors are interrelated to each other and act in a concerted, antagonistic, synergistic, or modulating way. Most important conclusions are summarized at the end of every reviewed subgroup. Genetic biomarkers or influences of various food components on concentration levels are not included in this review article.

  11. Evaluating clinical significance: incorporating robust statistics with normative comparison tests.

    PubMed

    van Wieringen, Katrina; Cribbie, Robert A

    2014-05-01

    The purpose of this study was to evaluate a modified test of equivalence for conducting normative comparisons when distribution shapes are non-normal and variances are unequal. A Monte Carlo study was used to compare the empirical Type I error rates and power of the proposed Schuirmann-Yuen test of equivalence, which utilizes trimmed means, with that of the previously recommended Schuirmann and Schuirmann-Welch tests of equivalence when the assumptions of normality and variance homogeneity are satisfied, as well as when they are not satisfied. The empirical Type I error rates of the Schuirmann-Yuen were much closer to the nominal α level than those of the Schuirmann or Schuirmann-Welch tests, and the power of the Schuirmann-Yuen was substantially greater than that of the Schuirmann or Schuirmann-Welch tests when distributions were skewed or outliers were present. The Schuirmann-Yuen test is recommended for assessing clinical significance with normative comparisons.

  12. Clinical significance of Aeromonas species isolated from patients with diarrhea.

    PubMed Central

    Moyer, N P

    1987-01-01

    A total of 248 strains of Aeromonas spp. were isolated from 3,334 human fecal specimens submitted to a state public health laboratory over a 2-year period to be cultured for enteric pathogens. Cary-Blair transport medium, blood ampicillin agar, and alkaline peptone water enrichment provided optimal recovery of Aeromonas spp. A questionnaire requesting clinical and epidemiological information was sent to physicians, who submitted stool samples for testing, with each laboratory report for 107 consecutive stool isolates of Aeromonas spp. The 56 questionnaires which were completed and returned were analyzed to determine the seasonal distribution of illness and the age and sex distribution of patients; characteristic symptoms; and predisposing factors for gastrointestinal disease caused by Aeromonas spp. It was concluded that some A. hydrophila, A. sobria, and A. caviae strains are capable of causing diarrhea and that antibiotic therapy and the drinking of untreated water are significant risk factors for susceptible hosts. PMID:3693537

  13. [A new possible strategy for prevention and preventive treatment of age-related macular degeneration resting on recent clinical and pathophysiological observations].

    PubMed

    Fischer, Tamás

    2009-03-15

    The beneficial effect achieved by the treatment of endothelial dysfunction in chronic cardiovascular diseases is already an evidence belonging to the basic treatment of the disease. Given the fact that the vascular system is uniform and consubstantial both physiologically, pathophysiologically and in terms of therapy, and that it plays a key role in age-related macular degeneration (AMD)--a disease leading to tragic loss of vision with its etiology and therapy being unknown--endothelial dysfunction should be treated. The pleiotropic effects of ACE-inhibitors, AR-blockers and statins and third generation beta blockers help to restitute the balance between vasodilators and vasoconstrictors in endothelial dysfunction caused by oxidative stress, the balance of growth factors and their inhibitors, pro- and anti-inflammatory substances and prothrombotic and fibrinolytic factors, inhibit the formation of oxidative stress and its harmful effects; while aspirin with its pleiotropic effects acting as an antiaggregation substance on platelets helps to set the endothelial layer back to its normal balance regarding its vasodilating, antithrombotic, antiadhesive and anti-inflammatory functions; trimetazidine as an adjuvant agent helps to normalize, to restore the disturbed metabolism of the retinal tissue functioning insufficiently, in the end. The angiotensin II receptor blocker telmisartan with its peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist effect inhibits the development of choroidal neovascularisation (CNV) and improves it clinically favourably. The third generation beta adrenergic receptor blocker carvedilol and nebivolol as well as the peroxisome proliferator-activated receptor-gamma agonist pioglitazone elicit their antioxidant vascular protective effects mitochondrially. For the above reasons it is suggested that, as a part of long term primary and/or secondary prevention, the following groups of patients with AMD receive--taking into

  14. Relationship between macular thickness measurement and signal strength using Stratus optical coherence tomography

    PubMed Central

    Segal, Ori; Shapira, Yinon; Gershoni, Assaf; Vainer, Igor; Nemet, Arie Y; Geffen, Noa; Mimouni, Michael

    2016-01-01

    Purpose To examine the relationship between signal strength and macular thickness as measured by Stratus optical coherence tomography (OCT)’s fast macular thickness protocol in healthy subjects. Methods In this prospective cross-sectional study 79 eyes of 42 healthy subjects were enrolled. The age, gender, and eye (right vs left) of each subject were recorded. The Stratus OCT fast macular thickness scan protocol was used and the macular thickness was measured with retinal thickness map analysis. Each eye was imaged at least six times to acquire images with signal strengths of 4, 5, 6, 7, 8, and 9 out of 10 via adjustment of the focusing knob. The OCT parameters included in the analysis were thickness in the central 1 mm and in the different quadrants in the 3-mm area. Results Overall 79 eyes of 42 patients with a mean age of 38.4±12.4 were included. There was no significant difference between the signal strength measurements obtained with different signal strengths in the central thickness (P=0.20). In the superior, nasal, inferior, and temporal quadrants, a signal strength of 8 demonstrated up to 3 µm thicker measurements than a signal strength of 5 (P<0.05). In general linear regression analysis, after accounting for age and gender, signal strength did not remain a significant predictor of thickness in any quadrant. Conclusions When using fast map macular measurements, a signal strength of 5 is clinically as efficient as a signal strength of 8 in measuring macular thickness in all quadrants. Insisting on higher signal strength may not be necessary. PMID:27956823

  15. Clinical Manifestations, Complications and Treatment of Ocular Sarcoidosis: Correlation between Visual Efficiency and Macular Edema as Seen on Optical Coherence Tomography.

    PubMed

    Paovic, Jelena; Paovic, Predrag; Sredovic, Vojislav; Jovanovic, Svetlana

    2016-09-14

    Sarcoidosis is a chronic systemic autoimmune disease which belongs to a group of systemic granulomatous diseases. It can be confirmed through characteristic systemic and ocular manifestations and histological findings. Biopsy is the golden standard for diagnosing sarcoidosis. Ocular sarcoidosis can be confirmed, probable, or possible. Over a two-year period, ocular manifestations were studied on a sample of 52 patients, each followed for four months and diagnosed with some form of systemic sarcoidosis. Most frequent systemic manifestations in patients with ocular sarcoidosis were pulmonary, skin, glandular, and systemic generalized sarcoidosis. The disease was diagnosed four times more frequently in females than males (42:10, respectively; p < 0.05). Most frequent, and statistically significant, manifestation of ocular sarcoidosis is anterior uveitis (64.61%; p < 0.01). Macular edema and periphlebitis associated with periarteritis were frequent, and statistically significant (43.90% and 29.26%, respectively; p < 0.05). Overall, with regards to gender and location (right eye; left eye), visual acuity was >0.5 and of statistical significance (76.92%; p < 0.01). The most common therapy consisted of systemic corticosteroids (26.67%) and/or a combination of corticosteroids and immunosuppressive drugs (23.33%). In 16 eyes treated with repeated doses of sub-Tenon's injections, both initial and control visual acuity correlated with average thickness. There was positive correlation between several optical coherence tomography findings before and after treatment.

  16. The Clinical Effectiveness and Cost-Effectiveness of Screening for Age-Related Macular Degeneration in Japan: A Markov Modeling Study

    PubMed Central

    Tamura, Hiroshi; Goto, Rei; Akune, Yoko; Hiratsuka, Yoshimune; Hiragi, Shusuke; Yamada, Masakazu

    2015-01-01

    Objective To investigate the cost-effectiveness of screening and subsequent intervention for age-related macular degeneration (AMD) in Japan. Methods The clinical effectiveness and cost-effectiveness of screening and subsequent intervention for AMD were assessed using a Markov model. The Markov model simulation began at the age of 40 years and concluded at the age of 90 years. The first-eye and second-eye combined model assumed an annual state-transition probability, development of prodromal symptoms, choroidal neovascularization (CNV), and reduction in visual acuity. Anti–vascular-endothelial-growth-factor (anti-VEGF) intravitreal injection therapy and photodynamic therapy (PDT) were performed to treat CNV. Intake of supplements was recommended to patients who had prodromal symptoms and unilateral AMD. Data on prevalence, morbidity, transition probability, utility value of each AMD patient, and treatment costs were obtained from published clinical reports. Results In the base-case analysis, screening for AMD every 5 years, beginning at the age of 50 years, showed a decrease of 41% in the total number of blind patients. The screening program reduced the incidence of blindness more than did the additional intake of supplements. However, the incremental cost-effectiveness ratio (ICER) of screening versus no screening was 27,486,352 Japanese yen (JPY), or 259,942 US dollars (USD) per quality-adjusted life year (QALY). In the sensitivity analysis, prodromal symptom-related factors for AMD had great impacts on the cost-effectiveness of screening. The lowest ICER obtained from the best scenario was 4,913,717 JPY (46,470 USD) per QALY, which was approximately equal to the willingness to pay in Japan. Conclusions Ophthalmologic screening for AMD in adults is highly effective in reducing the number of patients with blindness but not cost-effective as demonstrated by a Markov model based on clinical data from Japan. PMID:26214804

  17. Clinical significance of giant negative T waves in hypertrophic cardiomyopathy

    SciTech Connect

    Alfonso, F.; Nihoyannopoulos, P.; Stewart, J.; Dickie, S.; Lemery, R.; McKenna, W.J. )

    1990-04-01

    To assess the clinical significance of giant negative T waves in patients with hypertrophic cardiomyopathy from Western nations, clinical, echocardiographic, radionuclide and 48 h electrocardiographic (ECG) monitoring findings were compared in 27 patients with and 56 patients without giant negative T waves. Patients with giant negative T waves were older at diagnosis (43 +/- 15 versus 32 +/- 14 years, p less than 0.005), had greater ECG voltage (SV1 + RV5 = 57 +/- 20 versus 37 +/- 18 mm, p less than 0.001) and had a more vertical frontal plane axis (38.4 +/- 34 versus 13.4 +/- 45 degrees, p less than 0.05). Left ventricular wall thickness on two-dimensional echocardiography was similar at the mitral valve level (mean 16.5 +/- 4 versus 16.6 +/- 3 cm), but was greater at the papillary muscle level (mean 20.7 +/- 5 versus 17.6 +/- 3 mm, p less than 0.01) and apex (mean 23.3 +/- 5 versus 17.3 +/- 3 mm, p less than 0.001) in patients with giant negative T waves. Fewer patients with giant negative T waves had asymmetric septal hypertrophy (12 (44%) of 27 versus 36 (64%) of 56, p = 0.08) or systolic anterior motion of the mitral valve (4 (14%) of 27 versus 25 (45%) of 56, p less than 0.01), whereas left ventricular end-diastolic (44.1 +/- 6 versus 39.6 +/- 5 mm, p = 0.01) and end-systolic dimensions (27.8 +/- 4 versus 24 +/- 6 mm, p less than 0.05) were greater in this group. Nonsustained ventricular tachycardia was seen on ECG monitoring in 21% of patients in both groups.

  18. Clinical significance of metallothioneins in cell therapy and nanomedicine

    PubMed Central

    Sharma, Sushil; Rais, Afsha; Sandhu, Ranbir; Nel, Wynand; Ebadi, Manuchair

    2013-01-01

    Mammalian metallothioneins (MTs) are low molecular weight (6–7 kDa) cysteine-rich proteins that are specifically induced by metal nanoparticles (NPs). MT induction in cell therapy may provide better protection by serving as antioxidant, anti-inflammatory, antiapoptotic agents, and by augmenting zinc-mediated transcriptional regulation of genes involved in cell proliferation and differentiation. Liposome-encapsulated MT-1 promoter has been used extensively to induce growth hormone or other genes in culture and gene-manipulated animals. MTs are induced as a defensive mechanism in chronic inflammatory conditions including neurodegenerative diseases, cardiovascular diseases, cancer, and infections, hence can serve as early and sensitive biomarkers of environmental safety and effectiveness of newly developed NPs for clinical applications. Microarray analysis has indicated that MTs are significantly induced in drug resistant cancers and during radiation treatment. Nutritional stress and environmental toxins (eg, kainic acid and domoic acid) induce MTs and aggregation of multilamellar electron-dense membrane stacks (Charnoly body) due to mitochondrial degeneration. MTs enhance mitochondrial bioenergetics of reduced nicotinamide adenine dinucleotide–ubiquinone oxidoreductase (complex-1), a rate-limiting enzyme complex involved in the oxidative phosphorylation. Monoamine oxidase-B inhibitors (eg, selegiline) inhibit α-synuclein nitration, implicated in Lewy body formation, and inhibit 1-methyl 4-phenylpyridinium and 3-morpholinosydnonimine-induced apoptosis in cultured human dopaminergic neurons and mesencephalic fetal stem cells. MTs as free radical scavengers inhibit Charnoly body formation and neurodegenerative α-synucleinopathies, hence Charnoly body formation and α-synuclein index may be used as early and sensitive biomarkers to assess NP effectiveness and toxicity to discover better drug delivery and surgical interventions. Furthermore, pharmacological

  19. Geriatric vision loss due to cataracts, macular degeneration, and glaucoma.

    PubMed

    Eichenbaum, Joseph W

    2012-01-01

    The major causes of impaired vision in the elderly population of the United States are cataracts, macular degeneration, and open-angle glaucoma. Cataracts and macular degeneration usually reduce central vision, especially reading and near activities, whereas chronic glaucoma characteristically attacks peripheral vision in a silent way, impacting balance, walking, and driving. Untreated, these visual problems lead to issues with regard to taking medications, keeping track of finances and personal information, walking, watching television, and attending the theater, and often create social isolation. Thus, visually impaired individuals enter nursing homes 3 years earlier, have twice the risk of falling, and have 4× the risk of hip fracture. Consequently, many elderly with low vision exercise greater demands on community services. With the prospect of little improvement and sustained visual loss, in the face of poor tolerance of low-vision services and not accepting magnification as the only way to read, clinical depression is common. In many instances, however, early and accurate diagnosis can result in timely treatment and can preserve quality of life. This review will look at current diagnostic and therapeutic considerations. Currently, about 20.5 million people in the United States have cataracts. The number will reach 30 million by 2020. About 1.75 million Americans currently have some form of macular degeneration, and the number is estimated to increase to 2.95 million in 2020. Approximately 2.2 million Americans have glaucoma, and by 2020 that number is estimated to be close to 3.4 million people. It is projected that by 2030 there will be 72.1 million seniors. With some overlap of the above 3 groups conservatively estimated (if you add the 2030 cataract group to the macular degeneration and glaucoma groups), then about 1 in 2 senior individuals by 2030 may have some significant ocular disease, which could account for about 50% of the healthcare budget for the

  20. Cytochrome P450 structure, function and clinical significance: A review.

    PubMed

    Palrasu, Manikandan; Nagini, Siddavaram

    2017-01-25

    The cytochrome P450 (CYP) enzymes are membrane-bound hemoproteins that play a pivotal role in the detoxification of xenobiotics, cellular metabolism and homeostasis. Induction or inhibition of CYP enzymes is a major mechanism that underlies drug-drug interactions. CYP enzymes can be transcriptionally activated by various xenobiotics and endogenous substrates through receptor-dependent mechanisms. CYP enzyme inhibition is a principal mechanism for metabolism-based drug-drug interactions. Many chemotherapeutic drugs can cause drug interactions due to their ability to either inhibit or induce the CYP enzyme system. Predictions based on in silico analyses followed by validation have identified several microRNAs that regulate CYPs. Genetic polymorphisms and epigenetic changes in CYP genes may be responsible for inter-individual and inter-ethnic variations in disease susceptibility and the therapeutic efficacy of drugs. Knowledge about the substrates, inducers, inhibitors of CYP isoforms, and the polymorphisms of CYP enzymes may be used as an aid by clinicians to determine therapeutic strategy, and treatment doses for drugs that are metabolized by CYP gene products. The present review is a comprehensive compilation of cytochrome P450 structure, function, pharmacogenetics, and pharmacoepigenetics and clinical significance.

  1. Update on clinical significance of coagulase-negative staphylococci.

    PubMed Central

    Kloos, W E; Bannerman, T L

    1994-01-01

    The clinical significance of coagulase-negative Staphylococcus species (CNS) continues to increase as strategies in medical practice lead to more invasive procedures. Hospitalized patients that are immunocompromised and/or suffering from chronic diseases are the most vulnerable to infection. Since CNS are widespread on the human body and are capable of producing very large populations, distinguishing the etiologic agent(s) from contaminating flora is a serious challenge. For this reason, culture identification should proceed to the species and strain levels. A much stronger case can be made for the identification of a CNS etiologic agent if the same strain is repeatedly isolated from a series of specimens as opposed to the isolation of different strains of one or more species. Strain identity initially can be based on colony morphology, and then one or more molecular approaches can be used to gain information on the genotype. Many of the CNS species are commonly resistant to antibiotics that are being indicated for staphylococcal infections, with the exception of vancomycin. The widespread use of antibiotics in hospitals has provided a reservoir of antibiotic-resistant genes. The main focus on mechanisms of pathogenesis has been with foreign body infections and the role of specific adhesins and slime produced by Staphylococcus epidermidis. Slime can reduce the immune response and opsonophagocytosis, thereby interfering with host defense mechanisms. As we become more aware of the various strategies used by CNS, we will be in a better position to compromise their defense mechanisms and improve treatment. Images PMID:8118787

  2. Cataracts and macular degeneration.

    PubMed

    Shoch, D

    1979-09-01

    The intraocular lens restores general vision and some degree of independence and mobility to patients with dense cataracts and macular degeneration. The patient, however, must be repeatedly warned that fine central vision, particularly reading, will not be possible after the surgery. An aphakic spectacle leaves such patients a narrow band of vision when superimposed over the macular lesion, and contact lenses are too small for the patient to manage insertion without help.

  3. Construction of databases: advances and significance in clinical research.

    PubMed

    Long, Erping; Huang, Bingjie; Wang, Liming; Lin, Xiaoyu; Lin, Haotian

    2015-12-01

    Widely used in clinical research, the database is a new type of data management automation technology and the most efficient tool for data management. In this article, we first explain some basic concepts, such as the definition, classification, and establishment of databases. Afterward, the workflow for establishing databases, inputting data, verifying data, and managing databases is presented. Meanwhile, by discussing the application of databases in clinical research, we illuminate the important role of databases in clinical research practice. Lastly, we introduce the reanalysis of randomized controlled trials (RCTs) and cloud computing techniques, showing the most recent advancements of databases in clinical research.

  4. Acute Chorioamnionitis and Funisitis: Definition, Pathologic Features, and Clinical Significance

    PubMed Central

    Kim, Chong Jai; Romero, Roberto; Chaemsaithong, Piya; Chaiyasit, Noppadol; Yoon, Bo Hyun; Kim, Yeon Mee

    2015-01-01

    ; however, in fetuses, it is a risk factor for short- and long-term complications (i.e. neonatal sepsis, bronchopulmonary dysplasia, periventricular leukomalacia, and cerebral palsy). This article reviews the definition, pathogenesis, grading and staging, and clinical significance of the most common lesions in placental pathology. Illustrations of the lesions and diagrams of the mechanisms of disease are provided. PMID:26428501

  5. Optimizing the Anti-VEGF Treatment Strategy for Neovascular Age-Related Macular Degeneration: From Clinical Trials to Real-Life Requirements.

    PubMed

    Mantel, Irmela

    2015-06-01

    This Perspective discusses the pertinence of variable dosing regimens with anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) with regard to real-life requirements. After the initial pivotal trials of anti-VEGF therapy, the variable dosing regimens pro re nata (PRN), Treat-and-Extend, and Observe-and-Plan, a recently introduced regimen, aimed to optimize the anti-VEGF treatment strategy for nAMD. The PRN regimen showed good visual results but requires monthly monitoring visits and can therefore be difficult to implement. Moreover, application of the PRN regimen revealed inferior results in real-life circumstances due to problems with resource allocation. The Treat-and-Extend regimen uses an interval based approach and has become widely accepted for its ease of preplanning and the reduced number of office visits required. The parallel development of the Observe-and-Plan regimen demonstrated that the future need for retreatment (interval) could be reliably predicted. Studies investigating the observe-and-plan regimen also showed that this could be used in individualized fixed treatment plans, allowing for dramatically reduced clinical burden and good outcomes, thus meeting the real life requirements. This progressive development of variable dosing regimens is a response to the real-life circumstances of limited human, technical, and financial resources. This includes an individualized treatment approach, optimization of the number of retreatments, a minimal number of monitoring visits, and ease of planning ahead. The Observe-and-Plan regimen achieves this goal with good functional results. Translational Relevance: This perspective reviews the process from the pivotal clinical trials to the development of treatment regimens which are adjusted to real life requirements. The article discusses this translational process which- although not the classical interpretation of translation from fundamental to clinical research

  6. Age-related macular degeneration

    PubMed Central

    Querques, Giuseppe; Avellis, Fernando Onofrio; Querques, Lea; Bandello, Francesco; Souied, Eric H

    2011-01-01

    Clinical question: Is there any new knowledge about the pathogenesis and treatment of age-related macular degeneration (AMD)? Results: We now understand better the biochemical and pathological pathways involved in the genesis of AMD. Treatment of exudative AMD is based on intravitreal injection of new antivascular endothelial growth factor drugs for which there does not yet exist a unique recognized strategy of administration. No therapies are actually available for atrophic AMD, despite some experimental new pharmacological approaches. Implementation: strategy of administration, safety of intravitreal injection PMID:21654887

  7. Identification and Clinical Significance of Helcococcus kunzii in Human Samples

    PubMed Central

    Vergne, Anne; Guérin, François; Lienhard, Reto; Le Coustumier, Alain; Daurel, Claire; Isnard, Christophe; Marty, Nicole; Poyart, Claire

    2015-01-01

    From 2008 to 2013, 39 Helcococcus kunzii strains were collected from human clinical specimens (79% from foot ulcers), and 85% of the 39 patients were infected. Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry and molecular methods accurately identified all isolates. This large study of clinical observations confirms the potential pathogenic role of H. kunzii. PMID:25994161

  8. Identification and Clinical Significance of Helcococcus kunzii in Human Samples.

    PubMed

    Vergne, Anne; Guérin, François; Lienhard, Reto; Le Coustumier, Alain; Daurel, Claire; Isnard, Christophe; Marty, Nicole; Poyart, Claire; Cattoir, Vincent

    2015-08-01

    From 2008 to 2013, 39 Helcococcus kunzii strains were collected from human clinical specimens (79% from foot ulcers), and 85% of the 39 patients were infected. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and molecular methods accurately identified all isolates. This large study of clinical observations confirms the potential pathogenic role of H. kunzii.

  9. Clinical significance of J-wave in elite athletes.

    PubMed

    Pelliccia, Antonio; Quattrini, Filippo M

    2015-01-01

    The J-wave pattern on 12-lead ECG is traditionally defined as a positive deflection at junction between the end of the QRS and the beginning of the ST-segment. This pattern has recently been associated with increased risk for idiopathic ventricular fibrillation in the absence of cardiovascular disease. The interest for the clinical significance of J-wave pattern as a potential ECG hallmark of high risk for cardiac arrest has recently been reinforced by the growing practice of ECG screening, such as occurs in large population of young competitive athletes. The available scientific evidence shows that the J-wave pattern is relatively common in trained athletes (ranging from 14% to 44%) and, differently from subjects who suffered from ventricular fibrillation, commonly localized in lateral leads while it is relatively rare to be found in inferior leads. Furthermore the J-wave pattern has been demonstrated to be a dynamic phenomenon related to the training status, with the larger prominence at the peak of training and with an inverse relation between magnitude of J-wave and heart rate. In addition the J-wave pattern is usually associated with other ECG changes, such as increased QRS voltages and ST-segment elevation, as well as LV remodeling, suggesting that it likely represents another expression of the physiologic athlete's heart. Finally the scientific data available demonstrated that during a medium follow-up period the J-wave pattern does not convey risk for adverse cardiac events, including sudden death or ventricular tachyarrhythmias.

  10. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2017-01-12

    Age-Related Macular Degeneration (AMD); Macular Degeneration; Exudative Age-related Macular Degeneration; AMD; Macular Degeneration, Age-related, 10; Eye Diseases; Retinal Degeneration; Retinal Diseases

  11. Optical Coherence Tomography Measurement of Macular and Nerve Fiber Layer Thickness in Normal and Glaucomatous Human Eyes

    PubMed Central

    Guedes, Viviane; Schuman, Joel S.; Hertzmark, Ellen; Wollstein, Gadi; Correnti, Anthony; Mancini, Ronald; Lederer, David; Voskanian, Serineh; Velazquez, Leonardo; Pakter, Helena M.; Pedut-Kloizman, Tamar; Fujimoto, James G.; Mattox, Cynthia

    2007-01-01

    Purpose To evaluate the hypothesis that macular thickness correlates with the diagnosis of glaucoma. Design Cross-sectional study. Participants We studied 367 subjects (534 eyes), including 166 eyes of 109 normal subjects, 83 eyes of 58 glaucoma suspects, 196 eyes of 132 early glaucoma patients, and 89 eyes of 68 advanced glaucoma patients. Methods We used optical coherence tomography (OCT) to measure macular and nerve fiber layer (NFL) thickness and to analyze their correlation with each other and with glaucoma status. We used both the commercial and prototype OCT units and evaluated correspondence between measurements performed on the same eyes on the same days. Main Outcome Measure Macular and NFL thickness as measured by OCT. Results All NFL parameters both in prototype and commercial OCT units were statistically significantly different comparing normal subjects and either early or advanced glaucoma (P < 0.001). Inner ring, outer ring, and mean macular thickness both in prototype and commercial OCT devices were found to be significantly different between normal subjects and advanced glaucomatous eyes (P < 0.001). The outer ring was the only macular parameter that could significantly differentiate between normal and early glaucoma with either the prototype or commercial OCT unit (P = 0.003, P = 0.008, respectively). The area under the receiver operator characteristic (AROC) curves comparing mean NFL thickness between normal and advanced glaucomatous eyes was 1.00 for both the prototype and commercial OCT devices for eyes scanned on both machines on the same day. The AROC comparing mean macular thickness in normal and advanced glaucomatous eyes scanned on both machines on the same day was 0.88 for the prototype OCT device and 0.80 for the commercial OCT. Conclusions Both macular and NFL thickness as measured by OCT showed statistically significant correlations with glaucoma, although NFL thickness showed a stronger association than macular thickness. There was

  12. Clinical Significance of Symptoms in Smokers with Preserved Pulmonary Function

    PubMed Central

    Woodruff, Prescott G.; Barr, R. Graham; Bleecker, Eugene; Christenson, Stephanie A.; Couper, David; Curtis, Jeffrey L.; Gouskova, Natalia A.; Hansel, Nadia N.; Hoffman, Eric A.; Kanner, Richard E.; Kleerup, Eric; Lazarus, Stephen C.; Martinez, Fernando J.; Paine, Robert; Rennard, Stephen; Tashkin, Donald P.; Han, MeiLan K.

    2016-01-01

    BACKGROUND Currently, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) of less than 0.70 as assessed by spirometry after bronchodilator use. However, many smokers who do not meet this definition have respiratory symptoms. METHODS We conducted an observational study involving 2736 current or former smokers and controls who had never smoked and measured their respiratory symptoms using the COPD Assessment Test (CAT; scores range from 0 to 40, with higher scores indicating greater severity of symptoms). We examined whether current or former smokers who had preserved pulmonary function as assessed by spirometry (FEV1:FVC ≥0.70 and an FVC above the lower limit of the normal range after bronchodilator use) and had symptoms (CAT score, ≥10) had a higher risk of respiratory exacerbations than current or former smokers with preserved pulmonary function who were asymptomatic (CAT score, <10) and whether those with symptoms had different findings from the asymptomatic group with respect to the 6-minute walk distance, lung function, or high-resolution computed tomographic (HRCT) scan of the chest. RESULTS Respiratory symptoms were present in 50% of current or former smokers with preserved pulmonary function. The mean (±SD) rate of respiratory exacerbations among symptomatic current or former smokers was significantly higher than the rates among asymptomatic current or former smokers and among controls who never smoked (0.27± 0.67 vs. 0.08±0.31 and 0.03±0.21 events, respectively, per year; P<0.001 for both comparisons). Symptomatic current or former smokers, regardless of history of asthma, also had greater limitation of activity, slightly lower FEV1, FVC, and inspiratory capacity, and greater airway-wall thickening without emphysema according to HRCT than did asymptomatic current or former smokers. Among symptomatic current or former smokers, 42% used

  13. Volcano like pattern in optical coherence tomography in chronic diabetic macular edema.

    PubMed

    Pai, Sivakami A; Hussain, Nazimul; Hebri, Sudhira P; Lootah, Afra M; Dekhain, Moza A

    2014-04-01

    In this article we herein report an interesting vitreo-macular interface abnormality associated with chronic diabetic cystoid macular edema. It is an observational case study of three diabetic patients examined in the diabetic clinic. All the patients had proliferative diabetic retinopathy with chronic macular edema. A serial cross sectional OCT examination and tracking of both the longitudinal progression of macular thickening and vitreo-macular interface revealed cystoid macular edema with a characteristic hyperreflective vitreous shadow emerging from the vitreofoveal interface. All the patients had dehiscence of inner retinal layers. This particular morphological feature at the vitreo-foveolar interface, which we name as "volcano sign", has not been described earlier. The probable mechanism of such a finding probably could be due to slow progressive leakage of chronic cytoid fluid into the vitreous with condensation of the overlying vitreous. Vitreo-macular traction followed by posterior vitreous detachment probably would have contributed to such a morphological event.

  14. Granulocyte antigen systems and antibodies and their clinical significance

    SciTech Connect

    McCullough, J.

    1983-03-01

    Granulocyte alloantibodies and autoantibodies have a key role in the pathophysiology of several clinical problems. These include febrile transfusion reactions, severe pulmonary reactions to transfusion, isoimmune neonatal neutropenia, failure of effective granulocyte transfusion, autoimmune neutropenia, drug-induced neutropenia, and neutropenias secondary to many other diseases. Although many techniques are available for detecting granulocyte antibodies, the optimal in-vitro tests for predicting the antibodies' clinical effects are not established. Use of indium-111-labeled granulocytes may provide valuable information regarding the in-vivo effects of different granulocyte antibodies. Granulocyte transfusions continue to be used for a limited number of severely infected neutropenic patients who do not respond to antibiotic therapy.

  15. Clinical significance of recent inversion of the nipple: a reappraisal.

    PubMed Central

    Neville, E M; Freeman, A H; Adiseshiah, M

    1982-01-01

    In a retrospective survey of 63 cases of inverted nipple, unaccompanied by a palpable mass, 3 histologically confirmed carcinomas were found on combined clinical and mammographic examination - an incidence of 5%. No carcinoma was found in those patients under 50 years of age. The problem of the false negative mammogram is discussed. PMID:7069669

  16. [Acute life threatening catatonia--clinical significance and therapeutic possibilities].

    PubMed

    Bridler, R; Hell, D

    1997-09-13

    Malignant catatonia, associated with different somatic and psychiatric disorders, is a rare, life-threatening syndrome. Immediate recognition and adequate treatment are essential and may be life-saving. We describe a case of malignant catatonia and discuss the clinical implications. Additionally, we review the recent literature regarding epidemiology, nosology, current pathophysiological concepts, differential diagnosis, and treatment recommendations.

  17. Macular holes: vitreoretinal relationships and surgical approaches.

    PubMed

    Bainbridge, J; Herbert, E; Gregor, Z

    2008-10-01

    Idiopathic full-thickness macular holes develop as a result of anteroposterior and tangential traction exerted by the posterior vitreous cortex at the fovea. Vitreoretinal relationships during the development of macular holes can be demonstrated in detail by ocular coherence tomography, facilitating an improved understanding of their pathogenesis and guiding clinical management. Surgical strategies for the repair of macular holes are designed to relieve vitreofoveal traction and to promote flattening and reapposition of the macular hole edges by intraocular gas tamponade. A period of face-down positioning postoperatively is conventionally advised. However, the evidence to support this recommendation is weak and practice varies considerably. Surgical removal of the inner limiting membrane (ILM) is advocated to ensure thorough removal of any tangential tractional components including any residual cortical vitreous. Current evidence suggests that ILM peeling can improve anatomical outcomes but the effect on visual function is less predictable; unsuccessful attempts to peel the ILM can be associated with poor visual outcome. The use of vital dyes can facilitate visualisation of the ILM and help achieve complete, atraumatic peeling. Indocyanine green dye can enable high rates of macular hole closure but has been associated with poorer visual outcomes suggesting a dose-dependent toxicity. Trypan blue dye offers an alternative that may have a more favourable risk profile. An improved understanding of vitreoretinal relationships may facilitate a tailored approach to surgery in individuals with macular holes. Vitrectomy to relieve anteroposterior traction is central in the management of all full-thickness holes. The use of long-acting gases, prolonged face-down positioning, and ILM peeling may be more valuable for larger holes, longstanding holes, and those that have failed to close following conventional surgery.

  18. Value of optical coherence tomography in the detection of macular pathology before the removal of silicone oil

    PubMed Central

    Rashad, Mohammad Ahmad; Mohamed, Ahmed Abdel Aliem; Ahmed, Asmaa Ismail

    2016-01-01

    Purpose To assess the pathological macular changes with optical coherence tomography (OCT) before the removal of silicone oil (SiO) in eyes that had undergone pars plana vitrectomy for complicated forms of retinal detachment (RD). Patients and methods Subjects included 48 patients (51 eyes) with complicated RD including proliferative vitreoretinopathy, proliferative diabetic retinopathy, recurrent RD, penetrating trauma, uveitis, giant retinal tears, and macular holes. All the eyes had undergone SiO injection. Furthermore, all eyes had been planned for the removal of SiO 6–12 months after the primary surgery. Finally, all eyes had a fundus examination and OCT examination before the silicone oil removal. Results OCT findings indicated epiretinal membrane in 41% of the eyes, macular edema in 17%, macular detachment in 13.5%, macular thinning in 13.5%, macular holes in 10%, and subretinal membranes in 2%. Preoperative OCT was normal in only 12% of the eyes, while a clinical fundus examination was normal in 43% (P<0.001). Eyes with normal OCT had significantly better mean logMAR (0.35) than eyes with pathological changes detected through OCT (1.28; P<0.001). Surgical modifications were made during the removal of SiO in 74.5% of the eyes. Conclusion OCT detected significantly more pathological changes than a clinical fundus examination. This had an impact on both surgical step modification during the removal of SiO and predictability of visual outcome after the removal of SiO. PMID:26855558

  19. Bilateral macular injury from a green laser pointer.

    PubMed

    Dirani, Ali; Chelala, Elias; Fadlallah, Ali; Antonios, Rafic; Cherfan, George

    2013-01-01

    We report the case of a 13-year-old boy who had a bilateral macular injury after playing with a green laser pointer for a duration of 1 minute. Clinical examination revealed a decrease in visual acuity and macular injury in both eyes, and imaging investigations revealed a bilateral macular lesion due to exposure to the laser pointer. At 3 months' follow up, visual function had improved but remained partially impaired. This case emphasizes the importance of cautious and appropriate use of laser pointer devices because of the potential vision-threatening hazards induced by mishandling of these devices.

  20. Clinical significance of occult hepatitis B virus infection.

    PubMed

    Romero, Miriam; Madejón, Antonio; Fernández-Rodríguez, Conrado; García-Samaniego, Javier

    2011-03-28

    Occult hepatitis B virus (HBV) infection (OBI) is defined as the presence of HBV DNA in the liver (with or without detectable HBV DNA in serum) for individuals testing HBV surface antigen negative. Until recently, the clinical effect of OBI was unclear on the progression of liver disease; on the development of hepatocellular carcinoma; and on the risk for reactivation or transmission of HBV infection. Several studies suggest a high prevalence of OBI among patients with cryptogenic chronic liver disease, but its role in the progression to cirrhosis remains unclear. Although OBI has been well documented in human immunodeficiency virus (HIV)-positive patients, especially among those coinfected with hepatitis C virus, further studies are needed to determine its current clinical impact in HIV setting.

  1. Acrophialophora, a Poorly Known Fungus with Clinical Significance

    PubMed Central

    Sandoval-Denis, Marcelo; Sutton, Deanna A.; Wiederhold, Nathan P.; Guarro, Josep

    2015-01-01

    Acrophialophora fusispora is an emerging opportunistic fungus capable of causing human infections. The taxonomy of the genus is not yet resolved and, in order to facilitate identification of clinical specimens, we have studied a set of clinical and environmental Acrophialophora isolates by morphological and molecular analyses. This set included the available type strains of Acrophialophora species and similar fungi, some of which were considered by various authors to be synonyms of A. fusispora. Sequence analysis of the large subunit (LSU) and internal transcribed spacer (ITS) regions of the nuclear ribosomal DNA and a fragment of the β-tubulin (Tub) gene revealed that Acrophialophora belongs in the family Chaetomiaceae and comprises three different species, i.e., A. fusispora, Acrophialophora levis, and Acrophialophora seudatica; the latter was previously included in the genus Ampullifera. The most prevalent species among clinical isolates was A. levis (72.7%), followed by A. fusispora (27.3%), both of which were isolated mostly from respiratory specimens (72.7%), as well as subcutaneous and corneal tissue samples. In general, of the eight antifungal drugs tested, voriconazole had the greatest in vitro activity, while all other agents showed poor in vitro activity against these fungi. PMID:25716450

  2. Acrophialophora, a poorly known fungus with clinical significance.

    PubMed

    Sandoval-Denis, Marcelo; Gené, Josepa; Sutton, Deanna A; Wiederhold, Nathan P; Guarro, Josep

    2015-05-01

    Acrophialophora fusispora is an emerging opportunistic fungus capable of causing human infections. The taxonomy of the genus is not yet resolved and, in order to facilitate identification of clinical specimens, we have studied a set of clinical and environmental Acrophialophora isolates by morphological and molecular analyses. This set included the available type strains of Acrophialophora species and similar fungi, some of which were considered by various authors to be synonyms of A. fusispora. Sequence analysis of the large subunit (LSU) and internal transcribed spacer (ITS) regions of the nuclear ribosomal DNA and a fragment of the β-tubulin (Tub) gene revealed that Acrophialophora belongs in the family Chaetomiaceae and comprises three different species, i.e., A. fusispora, Acrophialophora levis, and Acrophialophora seudatica; the latter was previously included in the genus Ampullifera. The most prevalent species among clinical isolates was A. levis (72.7%), followed by A. fusispora (27.3%), both of which were isolated mostly from respiratory specimens (72.7%), as well as subcutaneous and corneal tissue samples. In general, of the eight antifungal drugs tested, voriconazole had the greatest in vitro activity, while all other agents showed poor in vitro activity against these fungi.

  3. Bacterial resistance to tetracycline: mechanisms, transfer, and clinical significance.

    PubMed Central

    Speer, B S; Shoemaker, N B; Salyers, A A

    1992-01-01

    Tetracycline has been a widely used antibiotic because of its low toxicity and broad spectrum of activity. However, its clinical usefulness has been declining because of the appearance of an increasing number of tetracycline-resistant isolates of clinically important bacteria. Two types of resistance mechanisms predominate: tetracycline efflux and ribosomal protection. A third mechanism of resistance, tetracycline modification, has been identified, but its clinical relevance is still unclear. For some tetracycline resistance genes, expression is regulated. In efflux genes found in gram-negative enteric bacteria, regulation is via a repressor that interacts with tetracycline. Gram-positive efflux genes appear to be regulated by an attenuation mechanism. Recently it was reported that at least one of the ribosome protection genes is regulated by attenuation. Tetracycline resistance genes are often found on transmissible elements. Efflux resistance genes are generally found on plasmids, whereas genes involved in ribosome protection have been found on both plasmids and self-transmissible chromosomal elements (conjugative transposons). One class of conjugative transposon, originally found in streptococci, can transfer itself from streptococci to a variety of recipients, including other gram-positive bacteria, gram-negative bacteria, and mycoplasmas. Another class of conjugative transposons has been found in the Bacteroides group. An unusual feature of the Bacteroides elements is that their transfer is enhanced by preexposure to tetracycline. Thus, tetracycline has the double effect of selecting for recipients that acquire a resistance gene and stimulating transfer of the gene. PMID:1423217

  4. Resistance to antivirals in human cytomegalovirus: mechanisms and clinical significance.

    PubMed

    Pérez, J L

    1997-09-01

    Long term therapies needed for managing human cytomegalovirus (HCMV) infections in immunosupressed patients provided the background for the emergence of the resistance to antivirals active against HCMV. In addition, laboratory selected mutants have also been readily achieved. Both clinical and laboratory resistant strains share the same determinants of resistance. Ganciclovir resistance may be due to a few mutations in the HCMV UL97 gene and/or viral DNA pol gene, the former being responsible for about 70% of clinical resistant isolates. Among them, V464, V594, S595 and F595 are the most frequent mutations. Because of their less extensive clinical use, much less is known about resistance to foscarnet and cidofovir (formerly, HPMPC) but in both cases, it has been associated to mutations in the DNA pol. Ganciclovir resistant strains showing DNA pol mutations are cross-resistant to cidofovir and their corresponding IC50 are normally higher than those from strains harboring only mutations at the UL97 gene. To date, foscarnet resistance seems to be independent of both ganciclovir and cidofovir resistance.

  5. Scotopic Microperimetry in the Early Diagnosis of Age-Related Macular Degeneration: Preliminary Study

    PubMed Central

    Pescosolido, Nicola

    2014-01-01

    Background. Recent clinical studies have shown that, in some degenerative retinal diseases, like age-related macular degeneration (AMD), the sensitivity of the rods decreases more rapidly than the sensitivity of the cones. The aim of this study was to evaluate if there is a correlation between the presence of hard drusen at the macular level and the rod damage responsible for the reduction in scotopic retinal sensitivity in subjects at risk for AMD. Methods. The authors selected 24 subjects (14 men and 10 women) with an average age of 67.25 ± 5.7 years. Macular hard drusen were present in 50% of the subjects at the fundus oculi exam. The researchers evaluated the retinal sensitivity to light in mesopic and scotopic conditions of each subject with an MP-1 scotopic microperimeter (MP-1S). Results. In subjects with hard drusen in the fundus oculi examination, there was a statistically significant reduction in scotopic retinal sensitivity, while the mesopic retinal sensitivity was not compromised. Conclusion. This study revealed how the presence of hard drusen at the macular level is associated with a reduction in scotopic retinal sensitivity compared to a control group of healthy subjects. Retinal functionality in a scotopic setting examined with MP-1S could be useful in early diagnosis of AMD. PMID:25548774

  6. Airway hyperresponsiveness in asthma: mechanisms, clinical significance, and treatment.

    PubMed

    Brannan, John D; Lougheed, M Diane

    2012-01-01

    Airway hyperresponsiveness (AHR) and airway inflammation are key pathophysiological features of asthma. Bronchial provocation tests (BPTs) are objective tests for AHR that are clinically useful to aid in the diagnosis of asthma in both adults and children. BPTs can be either "direct" or "indirect," referring to the mechanism by which a stimulus mediates bronchoconstriction. Direct BPTs refer to the administration of pharmacological agonist (e.g., methacholine or histamine) that act on specific receptors on the airway smooth muscle. Airway inflammation and/or airway remodeling may be key determinants of the response to direct stimuli. Indirect BPTs are those in which the stimulus causes the release of mediators of bronchoconstriction from inflammatory cells (e.g., exercise, allergen, mannitol). Airway sensitivity to indirect stimuli is dependent upon the presence of inflammation (e.g., mast cells, eosinophils), which responds to treatment with inhaled corticosteroids (ICS). Thus, there is a stronger relationship between indices of steroid-sensitive inflammation (e.g., sputum eosinophils, fraction of exhaled nitric oxide) and airway sensitivity to indirect compared to direct stimuli. Regular treatment with ICS does not result in the complete inhibition of responsiveness to direct stimuli. AHR to indirect stimuli identifies individuals that are highly likely to have a clinical improvement with ICS therapy in association with an inhibition of airway sensitivity following weeks to months of treatment with ICS. To comprehend the clinical utility of direct or indirect stimuli in either diagnosis of asthma or monitoring of therapeutic intervention requires an understanding of the underlying pathophysiology of AHR and mechanisms of action of both stimuli.

  7. [Etiology, pathophysiology and clinical significance of hereditary fructose intolerance].

    PubMed

    Fauth, U; Halmágyi, M

    1991-10-01

    Due to repeatedly described incidents in patients with undiscovered hereditary fructose intolerance, the application of fructose and sorbit-containing parenteral solutions is a topic vehemently discussed. This paper presents a survey of the literature dealing with the inborn defect of fructose-1-phosphate aldolase. The physiology and pathophysiology of fructose metabolism are described as well as the clinical appearance and diagnostic possibilities. The acute course of a fructose incompatibility is determined by a threatening decrease in the blood glucose level, which is attributed to the inhibition of several enzymes of glycolysis and gluconeogenesis by an intracellular accumulation of fructose-1-phosphate. Within hours a global functional breakdown of organs, which normally have the enzyme, occurs. The impairment of the liver function finds expression in a severe coagulopathy, the damage of the kidney leads to anuria. In chronic oral fructose supply, damage of the liver and small intestinal mucosa with corresponding gastrointestinal symptoms determine the clinical course. Concerning diagnosis, contrary to the liver biopsy and the fructose tolerance test, the mucosal biopsy with determination of fructose-1-phosphate aldolase activity has the advantage of greater specificity and is better tolerated by the patient. A total abstinence to fructose and sorbitol-containing solutions is not considered to be necessary when the rarity of the illness is taken into account and certain precautions are taken. These include a specific anamnesis of nutrition as well as a total abstinence from fructose and sorbitol in infants and in the unconscious patient. For clinical routine a simple fructose tolerance test is suggested.

  8. The clinical significance of creativity in bipolar disorder

    PubMed Central

    Murray, Greg; Johnson, Sheri L.

    2012-01-01

    Clinical implications of the high rates of creativity within bipolar disorder (BD) have not been explored. The aim of this review is to outline these implications by (i) reviewing evidence for the link between creativity and BD, (ii) developing a provisional model of mechanisms underpinning the creativity–BD link, (iii) describing unique challenges faced by creative-BD populations, and (iv) systematically considering evidence-based psychosocial treatments in the light of this review. While more research into the creativity–BD nexus is urgently required, treatment outcomes will benefit from consideration of this commonly occurring phenotype. PMID:20579791

  9. Clinically significant drug interactions with antacids: an update.

    PubMed

    Ogawa, Ryuichi; Echizen, Hirotoshi

    2011-10-01

    One may consider that drug-drug interactions (DDIs) associated with antacids is an obsolete topic because they are prescribed less frequently by medical professionals due to the advent of drugs that more effectively suppress gastric acidity (i.e. histamine H(2)-receptor antagonists [H2RAs] and proton pump inhibitors [PPIs]). Nevertheless, the use of antacids by ambulant patients may be ever increasing, because they are freely available as over-the-counter (OTC) drugs. Antacids consisting of weak basic substances coupled with polyvalent cations may alter the rate and/or the extent of absorption of concomitantly administered drugs via different mechanisms. Polyvalent cations in antacid formulations may form insoluble chelate complexes with drugs and substantially reduce their bioavailability. Clinical studies demonstrated that two classes of antibacterials (tetracyclines and fluoroquinolones) are susceptible to clinically relevant DDIs with antacids through this mechanism. Countermeasures against this type of DDI include spacing out the dosing interval - taking antacid either 4 hours before or 2 hours after administration of these antibacterials. Bisphosphonates may be susceptible to DDIs with antacids by the same mechanism, as described in the prescription information of most bisphosphonates, but no quantitative data about the DDIs are available. For drugs with solubility critically dependent on pH, neutralization of gastric fluid by antacids may alter the dissolution of these drugs and the rate and/or extent of their absorption. However, the magnitude of DDIs elicited by antacids through this mechanism is less than that produced by H2RAs or PPIs; therefore, the clinical relevance of such DDIs is often obscure. Magnesium ions contained in some antacid formulas may increase gastric emptying, thereby accelerating the rate of absorption of some drugs. However, the clinical relevance of this is unclear in most cases because the difference in plasma drug concentration

  10. Diabetic Macular Edema

    NASA Astrophysics Data System (ADS)

    Lobo, Conceição; Pires, Isabel; Cunha-Vaz, José

    The optical coherence tomography (OCT), a noninvasive and noncontact diagnostic method, was introduced in 1995 for imaging macular diseases. In diabetic macular edema (DME), OCT scans show hyporeflectivity, due to intraretinal and/or subretinal fluid accumulation, related to inner and/or outer blood-retinal barrier breakdown. OCT tomograms may also reveal the presence of hard exudates, as hyperreflective spots with a shadow, in the outer retinal layers, among others. In conclusion, OCT is a particularly valuable diagnostic tool in DME, helpful both in the diagnosis and follow-up procedure.

  11. Molecular Pathology of Hepatic Neoplasms: Classification and Clinical Significance

    PubMed Central

    Walther, Zenta; Jain, Dhanpat

    2011-01-01

    Recent technological advances have enabled investigators to characterize the molecular genetics and genomics of hepatic neoplasia in remarkable detail. From these studies, an increasing number of molecular markers are being identified that correlate with clinically important tumor phenotypes. This paper discusses current knowledge relevant to the molecular classification of epithelial primary hepatic tumors that arise in adults, including focal nodular hyperplasia (FNH), hepatocellular adenoma (HCA), hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and combined HCC-CC. Genetic analysis has defined molecular subtypes of HCA that are clinicopathologically distinct and can be distinguished through immunohistochemistry. Gene expression studies have identified molecular signatures of progression from dysplastic nodules (DNs) to early HCC in cirrhosis. Analyses of the mutational spectra, chromosomal aberrations and instability, transcriptomics, and microRNA profiles of HCC have revealed the existence of biologically distinct subtypes of this common malignancy, with prognostic implications. Molecular characterization of biliary and hepatic progenitor cell phenotypes in liver cancer has shed new light on the histogenesis of these tumors and has focused attention on novel therapeutic targets. In coming years, the molecular classification of hepatic neoplasms will be increasingly valuable for guiding patient care, as targeted therapies for liver cancer are developed and brought into clinical practice. PMID:21559202

  12. Lipoprotein ratios: Physiological significance and clinical usefulness in cardiovascular prevention

    PubMed Central

    Millán, Jesús; Pintó, Xavier; Muñoz, Anna; Zúñiga, Manuel; Rubiés-Prat, Joan; Pallardo, Luis Felipe; Masana, Luis; Mangas, Alipio; Hernández-Mijares, Antonio; González-Santos, Pedro; Ascaso, Juan F; Pedro-Botet, Juan

    2009-01-01

    Low-density lipoprotein (LDL) cholesterol concentration has been the prime index of cardiovascular disease risk and the main target for therapy. However, several lipoprotein ratios or “atherogenic indices” have been defined in an attempt to optimize the predictive capacity of the lipid profile. In this review, we summarize their pathophysiological aspects, and highlight the rationale for using these lipoprotein ratios as cardiovascular risk factors in clinical practice, specifying their cut-off risk levels and a target for lipid-lowering therapy. Total/high-density lipoprotein (HDL) cholesterol and LDL/HDL cholesterol ratios are risk indicators with greater predictive value than isolated parameters used independently, particularly LDL. Future recommendations regarding the diagnosis and treatment of dyslipidemia, including instruments for calculating cardiovascular risk or action guidelines, should include the lipoprotein ratios with greater predictive power which, in view of the evidence-based results, are none other than those which include HDL cholesterol. PMID:19774217

  13. Clinicopathologic correlations and significance of clinically occult mammary lesions.

    PubMed

    Schwartz, G F; Feig, S A; Patchefsky, A S

    1978-03-01

    Experience with 189 clinically occult, i.e., nonpalpable breast lesions is presented. The described technique of localization and excision all but guarantees removal of even the smallest radiographically suspicious findings with an inconspicuous incision and minimal breast deformity. The incidence of carcinoma encountered in these 189 biopsies is 27.5%. Axillary node metastases were present in less than 25% of the invasive nonpalpable cancers, approximately half of what might have been expected if the lesions had been discovered in the usual manner. There were no patients with axillary node metastases among those with in situ ductal or microinvasive ductal carcinomas. This implies a better prognosis and lower death rate from breast cancer in these patients. Screening programs employing mammography, designed to detect breast cancers in this pre-palpable stage, are encountered as a means of uncovering a higher proportion of such cancers at an earlier stage in their natural histories.

  14. [Clinically significant drug-drug interactions between analgesics and psychotopics].

    PubMed

    Strobach, Dorothea

    2012-07-01

    Combining analgesic and psychotropic drugs can lead to pharmacodynamic and pharmacokinetic drug interactions. Under treatment with several serotonergic substances serotonin syndrome can occur, e.g., with certain opioids and antidepressant drugs. Serotonin reuptake inhibitors also affect the serotonin level in platelets, this can raise the risk for gastrointestinal bleeding especially in combination with non-steroidal antirheumatic drugs. Anticholinergic effects and sedation are common side effects of psychotropic but also analgesic drugs with possible additive results. A wide range of interactions between analgesics and psychotropics can occure during metabolism, especially via the cytochrome-P-system. The clinical relevance of warnings on drug interactions from data banks has always to be judged for the individual patient.

  15. Clinical and biochemical significance of toxin production by Aeromonas hydrophila.

    PubMed

    Kindschuh, M; Pickering, L K; Cleary, T G; Ruiz-Palacios, G

    1987-05-01

    Production of cytotoxin and enterotoxin by Aeromonas strains obtained from stools of 50 children in Mexico and Texas and from blood of 9 children with sepsis was determined. Results were correlated with clinical features of infected children as well as with biochemical traits of Aeromonas strains. Cytotoxin was produced by 40 of 42 Aeromonas strains (95%) isolated from stools of children with diarrhea, by all 8 isolates from stools of well children, and by all 9 isolates from children with sepsis. There was no difference in the quantities (amount of cytotoxin per milligram of protein required to kill 50% of the cells) of cytotoxin produced and in clinical manifestations among the groups. None of the isolates produced a toxin that could be neutralized by antiserum raised against Shiga toxin produced by Shigella dysenteriae 1 60R. Heat-labile-like enterotoxin (LT) was produced by 26 of 42 stool isolates (62%), while only 1 of the 42 isolates (2%) produced enterotoxinlike activity in suckling mice; 65% of the cytotoxin-producing strains also produced an LT-like material. All strains from blood produced LT-like material, and 2 of 6 (33%) produced activity in suckling mice. All strains produced hemolysin; 37 of 57 (65%) were Voges-Proskauer positive; 27 of 57 (47%) were lysine decarboxylase positive by API 20E strips, none were positive for lysine decarboxylose production by lysin-iron agar slants at 24 h, but 17 of 54 (31%) were positive at 48 h. There was no correlation between biochemical reactions and enterotoxin or cytotoxin production. There appears to be no correlation between toxin production by Aeromonas spp. and gastroenteritis.

  16. Microcurrent stimulation in the treatment of dry and wet macular degeneration

    PubMed Central

    Chaikin, Laurie; Kashiwa, Kellen; Bennet, Michael; Papastergiou, George; Gregory, Walter

    2015-01-01

    Purpose To determine the safety and efficacy of the application of transcutaneous (transpalpebral) microcurrent stimulation to slow progression of dry and wet macular degeneration or improve vision in dry and wet macular degeneration. Methods Seventeen patients aged between 67 and 95 years with an average age of 83 years were selected to participate in the study over a period of 3 months in two eye care centers. There were 25 eyes with dry age-related macular degeneration (DAMD) and six eyes with wet age-related macular degeneration (WAMD). Frequency-specific microcurrent stimulation was applied in a transpalpebral manner, using two programmable dual channel microcurrent units delivering pulsed microcurrent at 150 µA for 35 minutes once a week. The frequency pairs selected were based on targeting tissues, which are typically affected by the disease combined with frequencies that target disease processes. Early Treatment Diabetic Retinopathy Study or Snellen visual acuity (VA) was measured before and after each treatment session. All treatment was administered in a clinical setting. Results Significant increases were seen in VA in DAMD (P=0.012, Wilcoxon one-sample test), but in WAMD, improvements did not reach statistical significance (P=0.059). In DAMD eyes, twice as many patients showed increase in VA (52%) compared to those showing deterioration (26%), with improvements being often sizeable, whereas deteriorations were usually very slight. In WAMD eyes, five of six (83%) patients showed an increase and none showed deterioration. Conclusion The substantial changes observed over this period, combined with continued improvement for patients who continued treatment once a month, are encouraging for future studies. The changes observed indicate the potential efficacy of microcurrent to delay degeneration and possibly improve age-related macular degeneration, both wet and dry. However, this study has no control arm, so results should be treated with caution

  17. Clinical and prognostic significance of coagulation assays in lung cancer.

    PubMed

    Tas, Faruk; Kilic, Leyla; Serilmez, Murat; Keskin, Serkan; Sen, Fatma; Duranyildiz, Derya

    2013-03-01

    Activation of coagulation and fibrinolysis is frequently encountered among cancer patients. Such tumors are supposed to be associated with higher risk of invasion, metastases and eventually worse outcome. The aim of this study is to explore the prognostic value of blood coagulation tests for lung cancer patients. The study comprised 110 lung cancer patients. Pretreatment blood coagulation tests including PT, aPTT, PTA, INR, D-dimer, fibrinogen levels and platelet counts were evaluated. The plasma level of all coagulation tests revealed statistically significant difference between patient and control group (p < 0.001). There was a significant association between D-Dimer levels and histological subtypes of NSCLC, pointing an elevated plasma D-dimer level in squamous cell cancer (p = 0.035). Patients with extensive stage SCLC exhibited evidently higher levels of D-Dimer, INR and PLT (p = 0.037, p = 0.042, p = 0.04, respectively). Prolongation of PT and INR had statistically significant adverse effect on survival (p = 0.05 and p = 0.014, respectively). Although prolonged aPTT and high levels of D-dimer was associated with worse survival, the difference was not statistically significant (p = 0.117, p = 0.104). Multivariate analysis revealed INR as the sole independent prognostic variable among coagulation parameters (p = 0.05). In conclusion, elevation of PT and INR are associated with decreased survival in lung cancer patients.

  18. Equine cyathostomins: a review of biology, clinical significance and therapy

    PubMed Central

    Corning, Susan

    2009-01-01

    The small strongyles of horses, also known as cyathostomins, are considered the most prevalent and pathogenic parasites of horses today. The clinical syndrome of larval cyathostominosis which occurs as a result of mass emergence of inhibited stages has a high fatality rate despite the best standard of care given to affected horses. Management of the challenge level of cyathostomins to prevent the syndrome is preferable. Many different management programmes have been tried over the past two decades, with mixed success. Programmes have relied heavily on repeated use of anthelmintic treatments throughout the life of a horse. The widespread incidence of resistance to certain anthelmintics is reducing these options. An understanding of the biology of cyathostomins, risk factors for infection and appropriate strategic use of still effective anthelmintics is essential for the future management of this parasite group. This review highlights the necessity to use currently available anthelmintics that are appropriately suited to the biology of cyathostomins, and to maintain heir efficacy through an appropriate treatment strategy. PMID:19778462

  19. Platelet-mimicry of cancer cells: epiphenomenon with clinical significance.

    PubMed

    Tímár, József; Tóvári, József; Rásó, Erzsébet; Mészáros, Livia; Bereczky, Bíborka; Lapis, Károly

    2005-01-01

    Stem cell mimicry of cancer cells has been known for a long time and is considered to be responsible for ectopic gene expressions. The stem cell characteristics of tumor cells are shown to be involved in epithelial-mesenchymal transition and in the phenomenon of vascular mimicry. Certain cancer types acquire a geno-phenotype closely resembling the platelets and express several megakaryocytic genes (adhesion receptors alpha IIb beta 3, thrombin receptor and PECAM/CD 31 and/or platelet-type 12-LOX) able to activate the coagulation cascade or the platelets themselves. Here we define these potentials as platelet mimicry of cancer cells typical of pancreatic, breast, prostate, colorectal and urogenital cancers and melanoma. Data all support that platelet mimicry of certain cancer types is an important factor in their hematogenous dissemination and provides an attractive therapeutic target. Besides the long-available preclinical data, clinical trials have only recently provided evidence that targeting platelet mimicry of cancers is an efficient way to prevent tumor progression. The systematic discovery of the markers of platelet mimicry in various cancer types and their molecular targeting may provide new supportive therapeutic modalities for the management of the progressing disease.

  20. Mammalian aquaporins: diverse physiological roles and potential clinical significance

    PubMed Central

    Verkman, A. S.

    2013-01-01

    Aquaporins have multiple distinct roles in mammalian physiology. Phenotype analysis of aquaporin-knockout mice has confirmed the predicted role of aquaporins in osmotically driven transepithelial fluid transport, as occurs in the urinary concentrating mechanism and glandular fluid secretion. Aquaporins also facilitate water movement into and out of the brain in various pathologies such as stroke, tumour, infection and hydrocephalus. A major, unexpected cellular role of aquaporins was revealed by analysis of knockout mice: aquaporins facilitate cell migration, as occurs in angiogenesis, tumour metastasis, wound healing, and glial scar formation. Another unexpected role of aquaporins is in neural function – in sensory signalling and seizure activity. The water-transporting function of aquaporins is likely responsible for these roles. A subset of aquaporins that transport both water and glycerol, the ‘aquaglyceroporins’, regulate glycerol content in epidermal, fat and other tissues. Mice lacking various aquaglyceroporins have several interesting phenotypes, including dry skin, resistance to skin carcinogenesis, impaired cell proliferation, and altered fat metabolism. The various roles of aquaporins might be exploited clinically by development of drugs to alter aquaporin expression or function, which could serve as diuretics, and in the treatment of brain swelling, glaucoma, epilepsy, obesity and cancer. PMID:18482462

  1. [Clinical significance of betadine vaginal suppository treatment in pregnancy].

    PubMed

    Gimes, G; Péter, F

    1997-11-01

    Clinical experience proved the efficacy of Betadine suppository in the treatment of bacterial vaginosis and mycotic infections of the vagina. Vaginal infections, frequently observed in pregnancy, can led to maternal and fetal complications, thus Betadine should be used both for prevention and therapy. One can ask if iodine absorbed from the vagina can influence the fetal thyroid function? 64 pregnant women received 7 day Betadine suppository (200 mg polyvidonum-iodine PVP) treatment for colpitis on 37-40 gestational week with excellent therapeutic result. TSH levels were measured by immunoassay in the serum of newborns 4-5 days after delivery, no signs of hypothyroidism were observed. Authors recommended 7 day Betadine vaginal suppository regimen for the prevention of intrauterine infections, treatment of mixed (bacterial, mycotical) vaginal infections, and restoration of the normal vaginal equilibrium of bacterias, since the risk of hypothyroidism is negligeable in mature newborns. In case of prematurity hypothyroidism is more frequently found also without iodine treatment therefore TSH level control is recommended in each case.

  2. Ventricular arrhythmias in congestive heart failure: clinical significance and management.

    PubMed Central

    Khoshnevis, G R; Massumi, A

    1999-01-01

    The benefit of defibrillator therapy has been well established for patients with LV dysfunction (ejection fraction less than 35%), coronary artery disease, NSVT, and inducible and nonsuppressible ventricular tachycardia. Implantable cardioverter-defibrillator therapy is also indicated for all CHF patients in NYHA functional classes I, II, and III who present with aborted sudden cardiac death, or ventricular fibrillation, or hemodynamically unstable ventricular tachycardia--and also in patients with syncope with no documented ventricular tachycardia but with inducible ventricular tachycardia at electrophysiology study. The ongoing MADIT II trial was designed to evaluate the benefit of prophylactic ICD implantation in these patients (ejection fraction less than 30%, coronary artery disease, and NSVT) without prior risk stratification by PES. The CABG Patch trial concluded that prophylactic placement of an ICD during coronary artery bypass grafting in patients with low ejection fraction and abnormal SAECG is not justifiable. Except for the indications described above, ICD implantation has not been proved to be beneficial as primary or secondary therapy. Until more data are available, patients should be encouraged to enroll in the ongoing clinical trials. PMID:10217470

  3. Clinical significance of hepatitis B surface antigen mutants

    PubMed Central

    Coppola, Nicola; Onorato, Lorenzo; Minichini, Carmine; Di Caprio, Giovanni; Starace, Mario; Sagnelli, Caterina; Sagnelli, Evangelista

    2015-01-01

    Hepatitis B virus (HBV) infection is a major public health problem in many countries, with nearly 300 million people worldwide carrying HBV chronic infection and over 1 million deaths per year due to cirrhosis and liver cancer. Several hepatitis B surface antigen (HBsAg) mutations have been described, most frequently due to a single amino acid substitution and seldom to a nucleotide deletion. The majority of mutations are located in the S region, but they have also been found in the pre-S1 and pre-S2 regions. Single amino acid substitutions in the major hydrophilic region of HBsAg, called the “a” determinant, have been associated with immune escape and the consequent failure of HBV vaccination and HBsAg detection, whereas deletions in the pre-S1 or pre-S2 regions have been associated with the development of hepatocellular carcinoma. This review article will focus on the HBsAg mutants and their biological and clinical implications. PMID:26644816

  4. INTRAVITREAL CORTICOSTEROIDS IN DIABETIC MACULAR EDEMA

    PubMed Central

    Bailey, Clare; Loewenstein, Anat; Massin, Pascale

    2015-01-01

    Purpose: To review the relationship between kinetics, efficacy, and safety of several corticosteroid formulations for the treatment of diabetic macular edema. Methods: Reports of corticosteroid use for the treatment of diabetic macular edema were identified by a literature search, which focused on the pharmacokinetics, efficacy, and safety of these agents in preclinical animal models and clinical trials. Results: Available corticosteroids for diabetic macular edema treatment include intravitreal triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. Because of differences in solubility and bioavailability, various delivery mechanisms are used. Bioerodible delivery systems achieve higher maximum concentrations than nonbioerodible formulations. There is a relationship between visual gains and drug persistence in the intravitreal compartment. Safety effects were more complex; level of intravitreal triamcinolone acetonide exposure is related to development of elevated intraocular pressure and cataract; this does not seem to be the case for dexamethasone, where two different doses showed similar mean intraocular pressure and incidence of cataract surgery. With fluocinolone acetonide, rates of intraocular pressure elevations requiring surgery seem to be dose related; rates of cataract extraction were similar regardless of dose. Conclusion: Available corticosteroids for diabetic macular edema exhibit different pharmacokinetic profiles that impact efficacy and adverse events and should be taken into account when developing individualized treatment plans. PMID:26352555

  5. Characterization of two unusual clinically significant Francisella strains.

    PubMed Central

    Clarridge, J E; Raich, T J; Sjösted, A; Sandström, G; Darouiche, R O; Shawar, R M; Georghiou, P R; Osting, C; Vo, L

    1996-01-01

    We have isolated two phenotypically distinct nonfastidious Francisella strains (Fx1 and Fx2) from the blood of compromised patients with pneumonia and compared them with eight other Francisella strains, including Francisella tularensis biovar tularensis, F. tularensis biovar novicida, and F. philomiragia. Our isolates grew well on sheep blood agar, chocolate agar, modified Thayer-Martin agar, and Trypticase soy agar. Fx1 and Fx2 were determined to be within the Francisella genus by cellular fatty acid analysis and by the utilization of glucose, production of H2S and catalase, and lack of motility, oxidase, nitrate reductase, and gelatinase. They were additionally shown to belong to the species F. tularensis by sequencing of two variable regions comprising approximately 500 nucleotides of the 16S rRNA gene. Also, RNA probe hybridization confirmed their belonging to the species F. tularensis. However, the new strains, which are not identical, are distinguished from other F. tularensis strains by growth characteristics, repetitive extragenic palindromic PCR fragment pattern, and some biochemical tests. Key biochemical differences included the findings that Fx1 was positive for beta-galactosidase and arabinose hydrolysis and that both strains were citrulline ureidase positive and glycerol negative. Commercial F. tularensis antiserum agglutinated stock F. tularensis strains but not Fx1, Fx2, F. tularensis biovar novicida, or F. philomiragia; serum from either patient failed to agglutinate or only weakly agglutinated commercial antigen but showed agglutination when tested against each patient's respective isolate. Fx1 and Fx2 produced beta-lactamase. Because of their good growth, negative serology, and biochemical profile, the organisms could be misidentified in the clinical laboratory if standard strategies or commercial identification systems are used. PMID:8818897

  6. Structure, function and clinical significance of transferrin receptors.

    PubMed

    Feelders, R A; Kuiper-Kramer, E P; van Eijk, H G

    1999-01-01

    Iron plays an essential role in a spectrum of metabolic processes. Cellular iron uptake is facilitated by transferrin receptor (TfR)-mediated endocytosis. In recent years more insight has been obtained in TfR physiology and the regulation of cellular iron homeostasis. The synthesis of TfR and the iron storage protein ferritin is regulated reciprocally at the post-transcriptional level according to the cellular iron status. As a result of externalization of TfR during the endocytic cycle, a soluble form of TfR can be detected in serum. The serum TfR (sTfR) level is closely related to erythroid TfR turnover and the prime determinants of the sTfR concentration are cellular iron demands and erythroid proliferation rate. In the absence of a hyperplastic erythropoiesis the sTfR level is a sensitive parameter of early tissue iron deficiency. The entire spectrum of body iron status can be assessed by measurement of serum ferritin and sTfR levels, with ferritin as marker of tissue iron stores and sTfR as index of tissue iron needs. The sTfR may be a promising tool to detect iron deficiency in inflammatory states and in the anaemia of chronic disease as its concentration is, in contrast to ferritin levels, not influenced by the acute phase response. Determination of sTfR levels may also improve assessment of body iron stores during pregnancy and in neonates. Finally, the sTfR may be a useful parameter to monitor erythropoiesis in various clinical settings, for instance in the prediction of the haematological response to erythropoietin treatment. However, standardization of the sTfR assay, with definition of reference and pathological ranges, is necessary for the definitive introduction of the sTfR as major parameter of iron metabolism.

  7. [Clinical significance of gastrointestinal decontamination under protected environment].

    PubMed

    Nagao, T; Yonekura, S; Komatsuda, M; Nozaki, H; Arimori, S; Sawamura, S; Ozawa, A; Sasaki, S

    1991-01-01

    Many infections are caused by the patient's own oro-intestinal microbial flora under a protected environment. Thirty-eight patients with acute leukemia and two patients with blast crisis of chronic myelocytic leukemia were treated under a protected environment with or without prophylactic antibiotics. Antibiotics used for decontamination were vancomycin (V), polymyxin B (P) and nystatin (N). The number of patients in the VPN, PN and the no antibiotic group were 13, 13 and 14, respectively. While the intestinal microbial flora was almost completely eliminated in VPN group, the number of bacteria decreased slightly in PN group. The mean number of pharyngeal and anorectal bacterial species decreased most markedly in the VPN group, but there were no significant differences among the three groups. The number of febrile days was significantly lower in the VPN and PN group than the no antibiotics group with neutrophil counts of less than 100 microliters. The average number of episodes of infection per patient was lowest in VPN group and highest in the no antibiotic group. These data indicate that VPN administration is effective for eliminating intestinal bacterial flora and resultantly protecting endogenous infections.

  8. Evaluation of Clinical Significance of Dermoscopy in Alopecia Areata

    PubMed Central

    Guttikonda, Akhila Sai; Aruna, Chintaginjala; Ramamurthy, D V S B; Sridevi, K; Alagappan, Senthil Kumar L

    2016-01-01

    Background: Alopecia areata (AA) is a common, chronic inflammatory disease characterized by nonscarring hair loss on the scalp or any hair-bearing area of the body. Recently, dermoscopy, a noninvasive diagnostic procedure, has been employed for the diagnosis of AA. Aim: To evaluate various dermoscopic patterns in AA and correlate these patterns with the disease activity and severity. Materials and Methods: Dermoscopy was performed on AA patients using DL1 dermoscope (magnification ×10 was used). The dermoscopic patterns recorded were analyzed to identify any correlation with the disease activity and severity. Results: A total of fifty patients of AA were recruited in the study. Female outnumbered males with the ratio being 1.173:1. Mean age of the patients was 25.06 years. Mean duration of disease was 14 months. The most common site involved was scalp (80%) and type noted was patchy (84%). Various dermoscopic patterns noted were yellow dots (YD) (88%), short vellus hair (66%), black dots (BD) (58%), broken hairs (BHs) (56%), tapering hair (TH) (26%), Coudability hairs (14%), pigtail hair (14%), and Pohl-Pinkus constrictions (2%). Statistically significant correlation was observed between BD, BHs, THs, and disease activity. No significant correlation was found between severity and any of the dermoscopic features. Conclusion: The most common dermoscopic pattern in our study was YD. Presence of BDs, BHs, and THs indicate active disease. Dermoscopic patterns were not affected by severity of the disease. PMID:27904180

  9. Expression and clinical significance of Sirt1 in colorectal cancer.

    PubMed

    Yu, Deng-Feng; Jiang, Su-Juan; Pan, Zhi-Peng; Cheng, Wei-Dong; Zhang, Wen-Jun; Yao, Xiao-Kun; Li, Yu-Cheng; Lun, Yong-Zhi

    2016-02-01

    The objective of the present study was to examine the expression of Silent information regulator 1 (Sirt1) in colorectal cancer and peritumoral normal mucosa tissue, and therefore analyze the role and molecular mechanism of Sirt1 in the pathogenesis of colorectal cancer. Colorectal cancer tissue specimens were employed as the experimental group, and adjacent normal mucosa tissues >5 cm from tumor lesions were used as the control group. The expression of Sirt1 was detected by the immunohistochemical streptavidin peroxidase detection method in paraffin-embedded sections, whilst Sirt1 protein expression was examined by western blot analysis in the fresh tissues. Sirt1 protein was primarily expressed in the nuclei of the tumor cells, and positive staining was brownish-yellow in color. The relative expression quantities of Sirt1 in the peritumoral normal rectal mucosa and rectal carcinoma were 1.15 and 2.62, and the differences between the two groups were statistically significant (P<0.05). The expression level of Sirt1 in colorectal carcinoma was significantly associated with the depth of tumor invasion, differentiation and tumor size (P<0.05). Sirt1 expression was also found to be associated with tumor tissue type, lymph node metastasis, Duke's stage and patient age. These characteristics combined may therefore be used as markers for the early diagnosis of colorectal cancer pathogenesis.

  10. Clinical and biological significance of circulating tumor cells in cancer.

    PubMed

    Masuda, Takaaki; Hayashi, Naoki; Iguchi, Tomohiro; Ito, Shuhei; Eguchi, Hidetoshi; Mimori, Koshi

    2016-03-01

    accumulated, adding to our body of knowledge on CTCs. In this review, we will summarize recent approaches to detect or capture CTCs. Moreover, we will introduce recent studies of the clinical and biological importance of CTCs and host cells.

  11. Relative density of urine: methods and clinical significance.

    PubMed

    Pradella, M; Dorizzi, R M; Rigolin, F

    1988-01-01

    The physical properties and chemical composition of urine are highly variable and are determined in large measure by the quantity and the type of food consumed. The specific gravity is the ratio of the density to that of water, and it is dependent on the number and weight of solute particles and on the temperature of the sample. The weight of solute particles is constituted mainly of urea (73%), chloride (5.4%), sodium (5.1%), potassium (2.4%), phosphate (2.0%), uric acid (1.7%), and sulfate (1.3%). Nevertheless, urine osmolality depends only on the number of solute particles. The renal production of maximally concentrated urine and formation of dilute urine may be reduced to two basic elements: (1) generation and maintenance of a renal medullary solute concentration hypertonic to plasma and (2) a mechanism for osmotic equilibration between the inner medulla and the collecting duct fluid. The interaction of the renal medullary countercurrent system, circulating levels of antidiuretic hormone, and thirst regulates water metabolism. Renin, aldosterone, prostaglandins, and kinins also play a role. Clinical estimation of the concentrating and diluting capacity can be performed by relatively simple provocative tests. However, urinary specific gravity after taking no fluids for 12 h overnight should be 1.025 or more, so that the second urine in the morning is a useful sample for screening purposes. Many preservation procedures affect specific gravity measurements. The concentration of solids (or water) in urine can be measured by weighing, hydrometer, refractometry, surface tension, osmolality, a reagent strip, or oscillations of a capillary tube. These measurements are interrelated, not identical. Urinary density measurement is useful to assess the disorders of water balance and to discriminate between prerenal azotemia and acute tubular necrosis. The water balance regulates the serum sodium concentration, therefore disorders are revealed by hypo- and hypernatremia. The

  12. The clinical significance of cereblon expression in multiple myeloma.

    PubMed

    Schuster, Steven R; Kortuem, K Martin; Zhu, Yuan Xiao; Braggio, Esteban; Shi, Chang-Xin; Bruins, Laura A; Schmidt, Jessica E; Ahmann, Greg; Kumar, Shaji; Rajkumar, S Vincent; Mikhael, Joseph; Laplant, Betsy; Champion, Mia D; Laumann, Kristina; Barlogie, Bart; Fonseca, Rafael; Bergsagel, P Leif; Lacy, Martha; Stewart, A Keith

    2014-01-01

    Cereblon (CRBN) mediates immunomodulatory drug (IMiD) action in multiple myeloma (MM). We demonstrate here that no patient with very low CRBN expression responded to IMiD plus dexamethasone therapy. In 53 refractory MM patients treated with pomalidomide and dexamethasone, CRBN levels predict for decreased response rates and significant differences in PFS (3.0 vs. 8.9 months, p<0.001) and OS (9.1 vs. 27.2 months, p=0.01) (lowest quartile vs. highest three quartiles). While higher CRBN levels can serve as a surrogate for low risk disease, our study demonstrates that low CRBN expression can predict resistance to IMiD monotherapy and is a predictive biomarker for survival outcomes.

  13. Bone cysts in sarcoidosis: what is their clinical significance?

    PubMed

    Yanardağ, Halil; Pamuk, Omer Nuri

    2004-09-01

    The incidence of bone cysts in sarcoidosis, a multisystemic disease, varies in different series, and these cysts are generally asymptomatic. We evaluated bone cysts in 516 sarcoidosis patients with available hand X-rays and in 200 patients with foot X-rays. Bone cysts were present in 21 cases (19 females, two males). The cysts were localized in phalanges of the hand in all cases, in feet in five cases, and in nasal bone in one. Six patients with bone cysts also had lupus pernio. Among those with cystic bone lesions, females were more frequent; extrapulmonary and skin involvement and lupus pernio were significantly more common. We diagnosed cystic bone lesions in 3.6% of our sarcoidosis patients and conclude that cysts were more frequent in females and in patients with lupus pernio.

  14. TRP channels in skin: from physiological implications to clinical significances

    PubMed Central

    Ho, Ji-Chen; Lee, Chih-Hung

    2015-01-01

    TRP channels are expressed in various cells in skin. As an organ system to border the host and environment, many nonneuronal cells, including epidermal keratinocytes and melanocytes, express several TRP channels functionally distinct from sensory processing. TRPV1 and TRPV3 in keratinocytes of the epidermis and hair apparatus inhibit proliferation, induce terminal differentiation, induce apoptosis, and promote inflammation. Activation of TRPV4, 6, and TRPA1 promotes regeneration of the severed skin barriers. TRPA1 also enhances responses in contact hypersensitivity. TRPCs in keratinocytes regulate epidermal differentiation. In human diseases with pertubered epidermal differentiation, the expression of TRPCs are altered. TRPMs, which contribute to melanin production in melanocytes, serve as significant prognosis markers in patients with metastatic melanoma. In summary, not only act in sensory processing, TRP channels also contribute to epidermal differentiation, proliferation, barrier integration, skin regeneration, and immune responses. In diseases with aberrant TRP channels, TRP channels might be good therapeutic targets. PMID:27493510

  15. Clinical significance of lymphadenectomy in patients with gastric cancer

    PubMed Central

    Tóth, Dezső; Plósz, János; Török, Miklós

    2016-01-01

    Approximately thirty percent of patients with gastric cancer undergo an avoidable lymph node dissection with a higher rate of postoperative complication. Comparing the D1 and D2 dissections, it was found that there is a significant difference in morbidity, favoured D1 dissection without any difference in overall survival. Subgroup analysis of patients with T3 tumor shows a survival difference favoring D2 lymphadenectomy, and there is a better gastric cancer-related death and non-statistically significant improvement of survival for node-positive disease in patients with D2 dissection. However, the extended lymphadenectomy could improve stage-specific survival owing to the stage migration phenomenon. The deployment of centralization and application of national guidelines could improve the surgical outcomes. The Japanese and European guidelines enclose the D2 lymphadenectomy as the gold standard in R0 resection. In the individualized, stage-adapted gastric cancer surgery the Maruyama computer program (MCP) can estimate lymph node involvement preoperatively with high accuracy and in addition the Maruyama Index less than 5 has a better impact on survival, than D-level guided surgery. For these reasons, the preoperative application of MCP is recommended routinely, with an aim to perform “low Maruyama Index surgery”. The sentinel lymph node biopsy (SNB) may decrease the number of redundant lymphadenectomy intraoperatively with a high detection rate (93.7%) and an accuracy of 92%. More accurate stage-adapted surgery could be performed using the MCP and SNB in parallel fashion in gastric cancer. PMID:26909128

  16. Clinical significance of Her2/neu overexpression in urothelial carcinomas.

    PubMed

    Alexa, Aurora; Baderca, Flavia; Zăhoi, Delia Elena; Lighezan, Rodica; Izvernariu, D; Raica, M

    2010-01-01

    HER2/neu is a defective transmembrane tyrosine kinase receptor, homologue to the epidermal growth factor receptor, showing overexpression in a large variety of tumor cells. There are no studies published so far regarding HER2/neu overexpression and sensitivity of the urothelial tumors of the urinary bladder to anti-HER2/neu therapy. There are a relatively high number of articles in the literature referring to HER2/neu expression in urothelial tumors of the urinary bladder, but only two of them had investigated HER2/neu expression in patients with urothelial tumors of the upper urinary tract. We have studied HER2/neu overexpression in 59 patients with urothelial carcinomas of the urinary tract by immunohistochemistry. Normal urothelium and the elements of the neighboring renal parenchyma were negative. Out of the 59 cases of urothelial carcinomas, 38 were negative (0 and +1) and 21 were positive: eight were moderately and 13 were intensely positive (+2 and +3). The percentage of positive cases was 35.59%. The negative cases were mostly well-differentiated, G1 tumors, no matter the T-tumor stage. Most of the cases were diagnosed as papillary or, rarely, infiltrative. There is no correlation between HER2/neu overexpression and the tumor stage. The same was true for the lymph node status. The expression intensity, however, was significantly correlated with the differentiation grade. Overexpression was most likely present in tumors with high differentiation grade (p<0.05).

  17. Asbestos and other ferruginous bodies: their formation and clinical significance.

    PubMed Central

    Churg, A. M.; Warnock, M. L.

    1981-01-01

    Analyses of asbestos bodies from the general population have confirmed that these structures, like asbestos bodies from the lungs of asbestos workers, contain an asbestos core. In members of the general population this core is almost always an amphibole, whereas asbestos workers may have bodies formed on either amphibole or chrysotile. Most adults have a few bodies, and increasing numbers are seen in blue collar workers and others who handle small amounts of the fiber, with the highest levels being seen in asbestos workers. In men with minimal or extensive occupational exposure, asbestos bodies are formed on the commercial fibers, amosite and crocidolite, whereas women also form a significant number of bodies on the noncommercial fibers, anthophyllite and tremolite. These findings suggest that women may be exposed to specific asbestos-containing products, eg, cosmetic talc. The commercial fibers found in women and white collar men probably reflect atmospheric pollution with asbestos. At the highest levels of exposure, numbers of asbestos bodies correlate in a general way with the presence of asbestosis, although no precise value has been determined above which asbestosis is always found. In persons with much lower or environmental exposure, there does not appear to be any correlation between numbers of bodies and disease, in particular between numbers of bodies and carcinoma of the lung or gastrointestinal tract. The situation for mesothelioma is uncertain. Images Figure 1 Figure 2 Figure 3 PMID:6101235

  18. Clinical Significance of Enteric Protozoa in the Immunosuppressed Human Population

    PubMed Central

    Stark, D.; Barratt, J. L. N.; van Hal, S.; Marriott, D.; Harkness, J.; Ellis, J. T.

    2009-01-01

    Summary: Globally, the number of immunosuppressed people increases each year, with the human immunodeficiency virus (HIV) pandemic continuing to spread unabated in many parts of the world. Immunosuppression may also occur in malnourished persons, patients undergoing chemotherapy for malignancy, and those receiving immunosuppressive therapy. Components of the immune system can be functionally or genetically abnormal as a result of acquired (e.g., caused by HIV infection, lymphoma, or high-dose steroids or other immunosuppressive medications) or congenital illnesses, with more than 120 congenital immunodeficiencies described to date that either affect humoral immunity or compromise T-cell function. All individuals affected by immunosuppression are at risk of infection by opportunistic parasites (such as the microsporidia) as well as those more commonly associated with gastrointestinal disease (such as Giardia). The outcome of infection by enteric protozoan parasites is dependent on absolute CD4+ cell counts, with lower counts being associated with more severe disease, more atypical disease, and a greater risk of disseminated disease. This review summarizes our current state of knowledge on the significance of enteric parasitic protozoa as a cause of disease in immunosuppressed persons and also provides guidance on recent advances in diagnosis and therapy for the control of these important parasites. PMID:19822892

  19. Clinical significance of acquired somatic mutations in aplastic anaemia.

    PubMed

    Marsh, J C W; Mufti, G J

    2016-08-01

    Aplastic anaemia (AA) is frequently associated with other disorders of clonal haemopoiesis such as paroxysmal nocturnal haemoglobinuria (PNH), myelodysplastic syndrome (MDS) and T-large granular lymphocytosis. Certain clones may escape the immune attack within the bone marrow environment and proliferate and attain a survival advantage over normal haemopoietic stem cells, such as trisomy 8, loss of heterozygosity of short arm of chromosome 6 and del13q clones. Recently acquired somatic mutations (SM), excluding PNH clones, have been reported in around 20-25 % of patients with AA, which predispose to a higher risk of later malignant transformation to MDS/acute myeloid leukaemia. Furthermore, certain SM, such as ASXL1 and DNMT3A are associated with poor survival following immunosuppressive therapy, whereas PIGA, BCOR/BCORL1 predict for good response and survival. Further detailed and serial analysis of the immune signature in AA is needed to understand the pathogenetic basis for the presence of clones with SM in a significant proportion of patients.

  20. Visual outcome of laser treatment in diabetic macular edema: Study from an Urban Diabetes Care Center

    PubMed Central

    Alvi, Rashid; Memon, Muhammad Saleh; Shera, Samad; Mumtaz, Seema N.; Shaikh, Sikander Ali; Fahim, Muhammad Faisal

    2016-01-01

    Objective: To determine the visual outcome of laser treatment in clinically significant macular edema. Methods: This interventional and qausi experimental study was carried out at Diabetic Association of Pakistan (DAP) during January 2011 and December 2012. Approval was taken from Research Ethical Committee of Isra Postgraduate Institute of Ophthalmology. Records of 925 eyes of 464 patients with “Clinical Significant macular edema” (CSME), treated with laser photocoagulation were analyzed. Best-corrected visual acuity (BCVA) at the time of presentation and at the last follow up, minimum of one year and maximum of 45 months was recorded and compared. SPSS version 20.0 was used to analyze the data. Results: Diabetic retinopathy was found in 20.3% (1777) of 8742 diabetic attending DAP Hospital” amongst whom 39.6% (705) had Sight threatening diabetic retinopathy. Laser was advised in 96.4% (680) individuals, accepted by 70.5% (480) individuals. Amongst 960 eyes of 480 patients who accepted laser, 925 eyes had clinically significant macular edema and 35 eyes had PDR who are not included in this study. Amongst 925 eyes with CSME, Grid laser was done in 913 eyes (99%) and focal laser was done in 12 eyes (1%). After a follow up of 12 to 45 months, it was found that best corrected visual acuity had declined in 2.4% (22) eyes, stabilized in 67% (619) eyes and improved in 30.7% (284) eyes. One line improvement on Snellen’s chart was fond in 21.3% (197) eyes, 2 lines in 8% (74) eyes, 3 lines in 1.2% (12) eyes and 4 lines in one (0.1%) eye with p-value of 0.000. Conclusion: Laser therapy is an effective treatment in stabilizing/improving the vision in diabetic macular edema particularly at those centers where only Argon Laser is available and OCF, FFA facilities do not exist. PMID:27882027

  1. What Is Age-Related Macular Degeneration?

    MedlinePlus

    ... of Low Vision Age-Related Macular Degeneration Vision Simulator AMD Pictures and Videos: What Does Macular Degeneration ... degeneration as part of the body's natural aging process. There are different kinds of macular problems, but ...

  2. Genetics Home Reference: Stargardt macular degeneration

    MedlinePlus

    ... Genetics Home Health Conditions Stargardt macular degeneration Stargardt macular degeneration Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Stargardt macular degeneration is a genetic eye disorder that causes progressive ...

  3. Macular ischaemia: a contraindication for anti-VEGF treatment in retinal vascular disease?

    PubMed

    Manousaridis, Kleanthis; Talks, James

    2012-02-01

    Anti-vascular endothelial growth factor (anti-VEGF) therapy has been shown to be effective at improving vision in patients with macular oedema due to diabetic retinopathy and vein occlusions, but blocking VEGF at least in theory could be detrimental to vascular integrity. For this reason, some patients with macular ischaemia were excluded from studies showing the effectiveness of therapy. A considerable number of patients present with mixed pathology of macular oedema and macular ischaemia and it is often impossible to determine the degree to which ischaemia accounts for decreased vision. In this review, the authors have dealt with the specific question of whether or not there is evidence to support potential worsening of the macular perfusion and visual function after anti-VEGF treatment with bevacizumab or ranibizumab for macular oedema secondary to diabetic retinopathy or retinal vein occlusions, especially if there is coexisting macular ischaemia. The authors conclude that anti-VEGF therapy rarely seems to further compromise the retinal circulation; however, worsening of macular ischaemia in the long term cannot be definitely excluded, particularly in eyes with significant ischaemia at baseline and after repeated intraocular anti-VEGF injections. The decision to offer prolonged anti-VEGF treatment in cases of significant coexisting macular ischaemia should not be based only on measurements of macular thickness; instead repeat fluorescein angiograms should be performed.

  4. Macular Amyloidosis and Epstein-Barr Virus

    PubMed Central

    Nahidi, Yalda; Tayyebi Meibodi, Naser; Meshkat, Zahra; Nazeri, Narges

    2016-01-01

    Background. Amyloidosis is extracellular precipitation of eosinophilic hyaline material of self-origin with special staining features and fibrillar ultrastructure. Macular amyloidosis is limited to the skin, and several factors have been proposed for its pathogenesis. Detection of Epstein-Barr virus (EBV) DNA in this lesion suggests that this virus can play a role in pathogenesis of this disease. Objective. EBV DNA detection was done on 30 skin samples with a diagnosis of macular amyloidosis and 31 healthy skin samples in the margin of removed melanocytic nevi by using PCR. Results. In patients positive for beta-globin gene in PCR, BLLF1 gene of EBV virus was positive in 23 patients (8 patients in case and 15 patients in the control group). There was no significant difference in presence of EBV DNA between macular amyloidosis (3.8%) and control (23.8%) groups (P = 0.08). Conclusion. The findings of this study showed that EBV is not involved in pathogenesis of macular amyloidosis. PMID:26981113

  5. Current Management of Traumatic Macular Holes

    PubMed Central

    Grzybowski, Andrzej

    2017-01-01

    Traumatic macular hole (TMH) is not a rare clinical condition, especially in young population. Its prognosis is of complexity and uncertainty, with a relatively high rate of spontaneous closure in some cases. Modern vitrectomy surgery plays an important role in the treatment of TMH, although the functional outcomes may be compromised by the concomitant retinal pathologies. Decision-making about the time of vitrectomy, especially in pediatric patients, remains to be clarified further. PMID:28239490

  6. Combination of Anti-VEGF and Laser Photocoagulation for Diabetic Macular Edema: A Review

    PubMed Central

    Garcia-Arumi, Jose; Boixadera, Anna

    2017-01-01

    Diabetic macular edema (DME) is the most common cause of vision loss in diabetic patients. Thirty years ago, the Early Treatment Diabetic Retinopathy Study (ETDRS) demonstrated that focal/grid laser photocoagulation reduces moderate vision loss from DME by 50% or more; thus, macular photocoagulation became the gold standard treatment for DME. However, with the development of anti-VEGF drugs (bevacizumab, ranibizumab, and aflibercept), better outcomes were obtained in terms of visual acuity gain and decrease in macular thickness in some studies when antiangiogenic drugs were administered in monotherapy. Macular laser therapy may still play an important role as an adjuvant treatment because it is able to improve macular thickness outcomes and reduce the number of injections needed. Here, we review some of the clinical trials that have assessed the efficacy of macular laser treatment, either as part of the treatment protocol or as rescue therapy. PMID:28348882

  7. Combination of Anti-VEGF and Laser Photocoagulation for Diabetic Macular Edema: A Review.

    PubMed

    Distefano, Laura N; Garcia-Arumi, Jose; Martinez-Castillo, Vicente; Boixadera, Anna

    2017-01-01

    Diabetic macular edema (DME) is the most common cause of vision loss in diabetic patients. Thirty years ago, the Early Treatment Diabetic Retinopathy Study (ETDRS) demonstrated that focal/grid laser photocoagulation reduces moderate vision loss from DME by 50% or more; thus, macular photocoagulation became the gold standard treatment for DME. However, with the development of anti-VEGF drugs (bevacizumab, ranibizumab, and aflibercept), better outcomes were obtained in terms of visual acuity gain and decrease in macular thickness in some studies when antiangiogenic drugs were administered in monotherapy. Macular laser therapy may still play an important role as an adjuvant treatment because it is able to improve macular thickness outcomes and reduce the number of injections needed. Here, we review some of the clinical trials that have assessed the efficacy of macular laser treatment, either as part of the treatment protocol or as rescue therapy.

  8. The combination of phacoemulsification surgery and intravitreal triamcinolone injection in patients with cataract and diabetic macular edema

    PubMed Central

    Ozgur, Ozlen Rodop; Ozkurt, Yelda; Kulekci, Zeynep; Evciman, Tufan

    2015-01-01

    Purpose To assess the safety and efficiency of combined phacoemulsification (PHACO) surgery and intravitreal triamcinolone (IVTA) injection with or without macular grid laser photocoagulation in patients with cataract and diabetic macular edema. Material and methods This prospective study included 41 eyes of 36 diabetic patients with cataract and coexisting clinically significant macular edema (CSME). After PHACO and IVTA injection eyes were divided into two groups: the laser and IVTA group (Group 1) and only IVTA group (Group 2). Preoperative and postoperative best corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were recorded. Paired sample t-test was used to compare data in the groups and C square test for qualitative variables. Results Postoperative BCVA was significantly higher than the initial BCVA during the follow-up period in both groups (p < 0.01). The BCVA 6 months after surgery was significantly higher in group 1 than in group 2 (p < 0.01). There was no statistically significant difference in IOP between two groups preoperatively and postoperatively during the follow-up period (p > 0.05). There was no statistically significant difference between both groups in mean CMT preoperatively and 2nd week, 2nd month and 3rd month after surgery (p > 0.05). The mean CMT 6 months after surgery was statistically significantly lower in group 1 than in group 2 (p < 0.01). Conclusions PHACO surgery combined with IVTA injection improves BCVA and provides a decrease in CMT in diabetic patients with CSME. Additional macular grid laser photocoagulation after surgery helps to preserve this improvement in BCVA and decrease in CMT. PMID:26949356

  9. A brief history of macular grids: from Thomas Reid to Edvard Munch and Marc Amsler.

    PubMed

    Marmor, M F

    2000-01-01

    Metamorphopsia is a symptom of retinal distortion from intrinsic retinal disease. It has undoubtedly been experienced for millennia, but its clinical significance has been appreciated only in modern times. The Norwegian painter Edvard Munch recognized scotomas and metamorphopsia after suffering an intraocular hemorrhage in his 60th year. Drawings made during this illness show his changing perceptions, and also his attempts to document them with a grid of lines. The Scottish philosopher Thomas Reid may have been the first to write about metamorphopsia. He described distortion of his vision in 1764, after an episode of sungazing, and recognized that the problem was probably of retinal origin. Lines or grids to document metamorphopsia have appeared in ophthalmology textbooks for more than 100 years, but testing for macular degeneration did not become routine until the dissemination of Amsler's grids in the middle of the 20th century. This is in large measure a result of developments in ophthalmology that made therapy for macular disease possible.

  10. Genetics and age-related macular degeneration: a practical review for the clinician

    PubMed Central

    Schwartz, Stephen G; Hampton, Blake M; Kovach, Jaclyn L; Brantley, Milam A

    2016-01-01

    Age-related macular degeneration is a complex disease, with both genetic and environmental risk factors interacting in unknown ways. Currently, 52 gene variants within 34 loci have been significantly associated with age-related macular degeneration. Two well-studied major genes are complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2). There exist several commercially available tests that are proposed to stratify patients into high-risk and low-risk groups, as well as predict response to nutritional supplementation. However, at present, the bulk of the available peer-reviewed evidence suggests that genetic testing is more useful as a research tool than for clinical management of patients. PMID:27445455

  11. The Macular Degeneration and Aging Study: Design and Research Protocol of a Randomized Trial for a Psychosocial Intervention with Macular Degeneration Patients

    PubMed Central

    Sörensen, Silvia; White, Katherine; Mak, Wingyun; Zanibbi, Katherine; Tang, Wan; O’Hearn, Amanda; Hegel, Mark T.

    2015-01-01

    Age-related Macular Degeneration (AMD) is the leading cause of irreversible and predictable blindness among older adults and creates serious physical and mental health consequences for this population. Visual impairment is associated with negative future outlook and depression and has serious consequences for older adults’ quality of life and, by way of depression, on long-term survival. Psychosocial interventions have the potential to alleviate and prevent depression symptoms among older AMD patients. We describe the protocol of the Macular Degeneration and Aging Study, a randomized clinical trial of a psychosocial Preventive Problem-Solving Intervention. The intervention is aimed at enhancing well-being and future planning among older adults with macular degeneration by increasing preparation for future care. Adequate randomization and therapeutic fidelity were achieved. Current retention rates were acceptable, given the vulnerability of the population. Acceptability (adherence and satisfaction) is high. Given the high public health significance and impact on quality of life among older adults with vision loss, this protocol contributes a valid test of a promising intervention for maintaining mental and physical health in this population. PMID:25812482

  12. Dosage dependency of intravitreal triamcinolone acetonide as treatment for diabetic macular oedema

    PubMed Central

    Spandau, U H M; Derse, M; Schmitz-Valckenberg, P; Papoulis, C; Jonas, J B

    2005-01-01

    Aim: To evaluate the effect of different doses of intravitreal triamcinolone acetonide on diffuse diabetic macular oedema. Methods: The prospective, randomised, double masked, clinical interventional study included 27 eyes (27 patients) with diffuse diabetic macular oedema. They were randomly divided into three study groups receiving an intravitreal injection of filtered triamcinolone acetonide of about 2 mg (n = 8 eyes), 5 mg (n = 10), or 13 mg (n = 9), respectively. Dosage measurement was performed before filtration. Mean follow up was 6.6 (SD 2.4) months (3–12 months). Main outcome measures were visual acuity and intraocular pressure. Results: Maximal increase in visual acuity was significantly (p = 0.046; 95% CI: 0.032 to 2.99; r = 0.38) correlated with the dosage of intravitreal triamcinolone acetonide. Additionally, the duration of the effect of intravitreal triamcinolone acetonide increased significantly with the dosage of intravitreal triamcinolone acetonide (r = 0.45; p = 0.014). Increase in intraocular pressure during follow up was statistically not significantly associated with the dosage used (p = 0.77). Conclusions: In patients with diffuse diabetic macular oedema receiving intravitreal triamcinolone acetonide, treatment response may last longer and be more pronounced with a dosage of 13 mg than in lower doses of 5 mg or 2 mg. Triamcinolone acetonide induced increase in intraocular pressure may not be markedly associated with the dosage used. PMID:16024853

  13. Consecutive macular edema and visual outcome in branch retinal vein occlusion.

    PubMed

    Baek, Sung Uk; Kwon, Soon Il; Park, In Won; Choi, Kyung Jun

    2014-01-01

    Purposes. The study introduced the concept of "consecutive macular edema" and evaluated the validity of visual outcome in macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Methods. Patients were categorized into the gainer group and the nongainer group according to the final visual acuity. We analyzed clinical characteristics involving total and consecutive duration of ME between the two groups. Results. Among the total 71 eyes of 71 patients, intravitreal bevacizumab injection (26 patients), triamcinolone (21), and natural course (33) were enrolled. The consecutive duration of ME was shorter in the gainer group than in the nongainer group (3.33 ± 1.50 and 5.24 ± 2.39 months; P = 0.000). After exclusion of macular ischemia, consecutive duration of ME in gainer group was also significantly shorter than in nongainer group (3.62 ± 1.60 and 6.11 ± 4.20 months; P = 0.010). Conclusions. The duration of ME in the nongainer group was longer than in the gainer group. In particular, the consecutive duration was an important factor in determining the final visual outcome. Clinical Trial Registration. Approval by Hallym University Sacred Heart Hospital Institutional Review Board/Ethics Committee was obtained for this retrospective study.

  14. Consecutive Macular Edema and Visual Outcome in Branch Retinal Vein Occlusion

    PubMed Central

    Baek, Sung Uk; Kwon, Soon Il; Park, In Won; Choi, Kyung Jun

    2014-01-01

    Purposes. The study introduced the concept of “consecutive macular edema” and evaluated the validity of visual outcome in macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Methods. Patients were categorized into the gainer group and the nongainer group according to the final visual acuity. We analyzed clinical characteristics involving total and consecutive duration of ME between the two groups. Results. Among the total 71 eyes of 71 patients, intravitreal bevacizumab injection (26 patients), triamcinolone (21), and natural course (33) were enrolled. The consecutive duration of ME was shorter in the gainer group than in the nongainer group (3.33 ± 1.50 and 5.24 ± 2.39 months; P = 0.000). After exclusion of macular ischemia, consecutive duration of ME in gainer group was also significantly shorter than in nongainer group (3.62 ± 1.60 and 6.11 ± 4.20 months; P = 0.010). Conclusions. The duration of ME in the nongainer group was longer than in the gainer group. In particular, the consecutive duration was an important factor in determining the final visual outcome. Clinical Trial Registration. Approval by Hallym University Sacred Heart Hospital Institutional Review Board/Ethics Committee was obtained for this retrospective study. PMID:24967098

  15. Simple Raman Instrument for in Vivo Detection of Macular Pigments

    PubMed Central

    ERMAKOV, IGOR V.; ERMAKOVA, MAIA R.; GELLERMANN, WERNER

    2011-01-01

    Raman spectroscopy holds promise as a novel noninvasive technology for the quantification of the macular pigments (MP) lutein and zeaxanthin. These compounds, which are members of the carotenoid family, are thought to prevent or delay the onset of age-related macular degeneration, the leading cause of irreversible blindness in the elderly. It is highly likely that they achieve this protection through their function as optical filters and/or antioxidants. Using resonant excitation in the visible region, we measure and quantify the Raman signals that originate from the carbon double bond (C=C) stretch vibrations of the π-conjugated molecule backbone. In this manuscript we describe the construction and performance of a novel compact MP Raman instrument utilizing dielectric angle-tuned band-pass filters for wavelength selection and a single-channel photo-multiplier for the detection of MP Raman responses. MP concentration measurements are fast and accurate, as seen in our experiments with model eyes and living human eyes. The ease and rapidity of Raman MP measurements, the simplicity of the instrumentation, the high accuracy of the measurements, and the lack of significant systematic errors should make this technology attractive for widespread clinical research. PMID:16053555

  16. Effect of blue light-filtering intraocular lens on color vision in patients with macular diseases after vitrectomy.

    PubMed

    Mokuno, Kumiko; Asami, Tetsu; Nonobe, Norie; Ito, Hirotaka; Fujiwara, Kumi; Terasaki, Hiroko

    2016-12-01

    To evaluate the color vision of patients with macular diseases after implanting a blue light-filtering intraocular lens (IOL) during vitrectomy. Twenty-seven patients had a blue light-filtering IOL implanted during vitrectomy for macular diseases (macular disease group), and 40 patients without macular disease had the same type of IOL implanted (non-macular disease group). The postoperative best-corrected visual acuity (BCVA) was ≥ 16/20 in all patients. The Farnsworth-Munsell 100-hue test was used to determine total error scores (TES) and mean error scores under photopic and mesopic conditions in both groups. The TES under mesopic conditions was significantly higher than that under photopic conditions in both groups (P < 0.05). However, the TES in the macular disease group was not significantly different from that of the non-macular disease group under both photopic and mesopic conditions. The mean error scores under photopic conditions for hues 11, 14, 16, 17, 18, and 20 (yellowish-red to yellow) were significantly higher in the macular disease group than in the non-macular disease group. The mean error scores for hues 7 and 85 (red) were significantly higher in the non-macular disease group than in the macular disease group. Under mesopic conditions, the mean error scores for hues 30, 60, and 61 were significantly higher in the non-macular disease group than in the macular disease group (P < 0.05). Our results indicate that blue light-filtering IOLs do not alter color discrimination in eyes with macular diseases, and these patients had good postoperative BCVA even under mesopic conditions.

  17. Influence of anti-VEGF about cardiovascular biomarkers in age related macular degeneration.

    PubMed

    Manresa, N; Mulero, J; Losada, M; Zafrilla, P

    2015-02-01

    Systemic VEGF inhibition disrupts endothelial homeostasis and accelerates the atherogenesis, suggesting that these events contribute to the clinical cardiovascular adverse events of VEGF-inhibiting therapies. The objective of the current study was to analyze the effect of anti-VEGF therapy on cardiovascular risk factors in patients with exudative age related macular degeneration. A total of 73 patients with exudative age related macular degeneration (without previous anti-VEGF therapy) were treated with two anti-VEGF: Ranibizumab and Pegaptanib sodium. The follow up was 6 months. The following parameters were determined before and after treatment: homocysteine, lipids (total cholesterol, triglycerides, HDL-c, LDL-c), C-Reactive Protein and fibrinogen. There were not statistically significant differences in parameters studied before and after treatment with both Pegaptanib sodium and Ranibizumab, except C-Reactive Protein. Of all patients analyzed, only 3 of them have initially C-Reactive Protein levels above normal levels and after antiangiogenic therapy, there was a significant increase in C-Reactive Protein. We have not found results in our study who to suspect that treatment with anti-VEGF in the patients with exudative age related macular degeneration increases cardiovascular risk predictors. However, after therapy was increased the CRP and fibrinogen may mean that anti-VEGF contribute an alteration of endothelial homeostasis in exudative AMD.

  18. Macular sub-layer thinning and association with pulmonary function tests in Amyotrophic Lateral Sclerosis

    PubMed Central

    Simonett, Joseph M.; Huang, Russell; Siddique, Nailah; Farsiu, Sina; Siddique, Teepu; Volpe, Nicholas J.; Fawzi, Amani A.

    2016-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder that may have anterior visual pathway involvement. In this study, we compare the macular structure of patients with ALS to healthy controls, and examine correlations between macular sub-layer thickness measurements and pulmonary function tests and disease duration. ALS patients underwent optical coherence tomography (OCT) imaging to obtain macular cube scans of the right eye. Macular cube OCT data from age-matched healthy subjects were provided by the OCT reading center. Semi-automated retinal segmentation software was used to quantify macular sub-layers. Pulmonary function tests and time since symptom onset were collected retrospectively from the electronic medical records of ALS patients. Macular retinal nerve fiber layer was significantly thinner in ALS patients compared to healthy controls (P < 0.05). Total macular and other sub-layer thicknesses were not reduced in the ALS cohort. Macular retinal nerve fiber layer thickness positively correlated with forced vital capacity % predicted and forced expiratory volume in 1 second % predicted (P < 0.05). In conclusion, analysis of OCT measurements supports the involvement of the anterior visual pathway in ALS. Subtle structural thinning in the macular retinal nerve fiber layer correlates with pulmonary function tests. PMID:27383525

  19. A Randomized, Placebo-Controlled, Clinical Trial of High-Dose Supplementation With Vitamins C and E, Beta Carotene, and Zinc for Age-Related Macular Degeneration and Vision Loss

    PubMed Central

    2006-01-01

    Background Observational and experimental data suggest that antioxidant and/or zinc supplements may delay progression of age-related macular degeneration (AMD) and vision loss. Objective To evaluate the effect of high-dose vitamins C and E, beta carotene, and zinc supplements on AMD progression and visual acuity. Design The Age-Related Eye Disease Study, an 11-center double-masked clinical trial, enrolled participants in an AMD trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral geographic atrophy, or pigment abnormalities in 1 or both eyes, or advanced AMD or vision loss due to AMD in 1 eye. At least 1 eye had best-corrected visual acuity of 20/32 or better. Participants were randomly assigned to receive daily oral tablets containing: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg); (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo. Main Outcome Measures (1)Photographic assessment of progression to or treatment for advanced AMD and (2) at least moderate visual acuity loss from baseline (≥15 letters). Primary analyses used repeated-measures logistic regression with a significance level of .01, unadjusted for covariates. Serum level measurements, medical histories, and mortality rates were used for safety monitoring. Results Average follow-up of the 3640 enrolled study participants, aged 55–80 years, was 6.3 years, with 2.4% lost to follow-up. Comparison with placebo demonstrated a statistically significant odds reduction for the development of advanced AMD with antioxidants plus zinc (odds ratio [OR], 0.72; 99% confidence interval [CI], 0.52–0.98). The ORs for zinc alone and antioxidants alone are 0.75 (99% CI, 0.55–1.03) and 0.80 (99% CI, 0.59–1.09), respectively. Participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% 5-year probability of progression to

  20. Confidence Intervals for Effect Sizes: Compliance and Clinical Significance in the "Journal of Consulting and Clinical Psychology"

    ERIC Educational Resources Information Center

    Odgaard, Eric C.; Fowler, Robert L.

    2010-01-01

    Objective: In 2005, the "Journal of Consulting and Clinical Psychology" ("JCCP") became the first American Psychological Association (APA) journal to require statistical measures of clinical significance, plus effect sizes (ESs) and associated confidence intervals (CIs), for primary outcomes (La Greca, 2005). As this represents the single largest…

  1. Body Dysmorphic Disorder and Other Clinically Significant Body Image Concerns in Adolescent Psychiatric Inpatients: Prevalence and Clinical Characteristics

    ERIC Educational Resources Information Center

    Dyl, Jennifer; Kittler, Jennifer; Phillips, Katharine A.; Hunt, Jeffrey I.

    2006-01-01

    Background: This study assessed prevalence and clinical correlates of body dysmorphic disorder (BDD), eating disorders (ED), and other clinically significant body image concerns in 208 consecutively admitted adolescent inpatients. It was hypothesized that adolescents with BDD would have higher levels of depression, anxiety, and suicidality.…

  2. Age-Related Macular Degeneration

    MedlinePlus

    ... version of this page please turn Javascript on. Age-related Macular Degeneration About AMD Click for more ... a leading cause of vision loss among people age 60 and older. It causes damage to the ...

  3. Incidence and risk factors for cystoid macular edema following scleral buckling.

    PubMed

    Lai, T-T; Huang, J-S; Yeh, P-T

    2016-12-09

    PurposeTo investigate the incidence of cystoid macular edema (CME) after scleral buckling (SB) and verify the possible risk factors of CME.MethodsA retrospective, non-comparative, interventional case series study was conducted. Clinical charts of 130 consecutive patients who were underwent successful SB for primary retinal detachment (RD) from 2009 to 2013 were reviewed. Optical coherence tomography (OCT) was applied to detect CME. Data pertaining to patient demographics, pre- and postoperative visual acuity, surgical procedures, and postoperative OCT findings were recorded. Factors associated with CME were also analyzed.ResultsThe incidence of CME was 9/130 (6.9%). Risk factors for developing CME were older age (non-CME vs CME: 44.8±14.8 vs 57.3±5.3 years, P<0.05), more extensive RD (RD extent by clock hours; non-CME vs CME: 4.61±1.57 vs 5.78±1.39, P<0.05), macular detachment (non-CME vs CME: 51.2 vs 88.9%, P<0.05), and external drainage (non-CME vs CME: 38.8% vs 77.8%, P<0.05). There was no significant difference between patient with and without CME regarding the use of gas tamponade and the lens status. In patients with more extensive RD (macular detachment plus RD of more than 3 clock hours before surgery), 8 of 68 patients had CME after SB and only older age and external drainage factors were associated with CME.ConclusionsThe risk factors associated with CME after SB were older age, more extended RD, macular detachment, and external drainage. External drainage should be used with caution in older patients with more extensive RD.Eye advance online publication, 9 December 2016; doi:10.1038/eye.2016.264.

  4. Use of electronic data and existing screening tools to identify clinically significant obstructive sleep apnea

    PubMed Central

    Severson, Carl A; Pendharkar, Sachin R; Ronksley, Paul E; Tsai, Willis H

    2015-01-01

    OBJECTIVES: To assess the ability of electronic health data and existing screening tools to identify clinically significant obstructive sleep apnea (OSA), as defined by symptomatic or severe OSA. METHODS: The present retrospective cohort study of 1041 patients referred for sleep diagnostic testing was undertaken at a tertiary sleep centre in Calgary, Alberta. A diagnosis of clinically significant OSA or an alternative sleep diagnosis was assigned to each patient through blinded independent chart review by two sleep physicians. Predictive variables were identified from online questionnaire data, and diagnostic algorithms were developed. The performance of electronically derived algorithms for identifying patients with clinically significant OSA was determined. Diagnostic performance of these algorithms was compared with versions of the STOP-Bang questionnaire and adjusted neck circumference score (ANC) derived from electronic data. RESULTS: Electronic questionnaire data were highly sensitive (>95%) at identifying clinically significant OSA, but not specific. Sleep diagnostic testing-determined respiratory disturbance index was very specific (specificity ≥95%) for clinically relevant disease, but not sensitive (<35%). Derived algorithms had similar accuracy to the STOP-Bang or ANC, but required fewer questions and calculations. CONCLUSIONS: These data suggest that a two-step process using a small number of clinical variables (maximizing sensitivity) and objective diagnostic testing (maximizing specificity) is required to identify clinically significant OSA. When used in an online setting, simple algorithms can identify clinically relevant OSA with similar performance to existing decision rules such as the STOP-Bang or ANC. PMID:26083542

  5. Mouse genetics and proteomic analyses demonstrate a critical role for complement in a model of DHRD/ML, an inherited macular degeneration

    PubMed Central

    Garland, Donita L.; Fernandez-Godino, Rosario; Kaur, Inderjeet; Speicher, Kaye D.; Harnly, James M.; Lambris, John D.; Speicher, David W.; Pierce, Eric A.

    2014-01-01

    Macular degenerations, inherited and age related, are important causes of vision loss. Human genetic studies have suggested perturbation of the complement system is important in the pathogenesis of age-related macular degeneration. The mechanisms underlying the involvement of the complement system are not understood, although complement and inflammation have been implicated in drusen formation. Drusen are an early clinical hallmark of inherited and age-related forms of macular degeneration. We studied one of the earliest stages of macular degeneration which precedes and leads to the formation of drusen, i.e. the formation of basal deposits. The studies were done using a mouse model of the inherited macular dystrophy Doyne Honeycomb Retinal Dystrophy/Malattia Leventinese (DHRD/ML) which is caused by a p.Arg345Trp mutation in EFEMP1. The hallmark of DHRD/ML is the formation of drusen at an early age, and gene targeted Efemp1R345W/R345W mice develop extensive basal deposits. Proteomic analyses of Bruch's membrane/choroid and Bruch's membrane in the Efemp1R345W/R345W mice indicate that the basal deposits comprise normal extracellular matrix (ECM) components present in abnormal amounts. The proteomic analyses also identified significant changes in proteins with immune-related function, including complement components, in the diseased tissue samples. Genetic ablation of the complement response via generation of Efemp1R345W/R345W:C3−/− double-mutant mice inhibited the formation of basal deposits. The results demonstrate a critical role for the complement system in basal deposit formation, and suggest that complement-mediated recognition of abnormal ECM may participate in basal deposit formation in DHRD/ML and perhaps other macular degenerations. PMID:23943789

  6. Mouse genetics and proteomic analyses demonstrate a critical role for complement in a model of DHRD/ML, an inherited macular degeneration.

    PubMed

    Garland, Donita L; Fernandez-Godino, Rosario; Kaur, Inderjeet; Speicher, Kaye D; Harnly, James M; Lambris, John D; Speicher, David W; Pierce, Eric A

    2014-01-01

    Macular degenerations, inherited and age related, are important causes of vision loss. Human genetic studies have suggested perturbation of the complement system is important in the pathogenesis of age-related macular degeneration. The mechanisms underlying the involvement of the complement system are not understood, although complement and inflammation have been implicated in drusen formation. Drusen are an early clinical hallmark of inherited and age-related forms of macular degeneration. We studied one of the earliest stages of macular degeneration which precedes and leads to the formation of drusen, i.e. the formation of basal deposits. The studies were done using a mouse model of the inherited macular dystrophy Doyne Honeycomb Retinal Dystrophy/Malattia Leventinese (DHRD/ML) which is caused by a p.Arg345Trp mutation in EFEMP1. The hallmark of DHRD/ML is the formation of drusen at an early age, and gene targeted Efemp1(R345W/R345W) mice develop extensive basal deposits. Proteomic analyses of Bruch's membrane/choroid and Bruch's membrane in the Efemp1(R345W/R345W) mice indicate that the basal deposits comprise normal extracellular matrix (ECM) components present in abnormal amounts. The proteomic analyses also identified significant changes in proteins with immune-related function, including complement components, in the diseased tissue samples. Genetic ablation of the complement response via generation of Efemp1(R345W/R345W):C3(-/-) double-mutant mice inhibited the formation of basal deposits. The results demonstrate a critical role for the complement system in basal deposit formation, and suggest that complement-mediated recognition of abnormal ECM may participate in basal deposit formation in DHRD/ML and perhaps other macular degenerations.

  7. [Detection of cystoid macular edema with orally administered fluorescein].

    PubMed

    Hütz, W; Hessemer, V; Jacobi, K W

    1989-10-01

    To detect cystoid macular edema after extracapsular cataract extraction, the authors used indirect ophthalmoscopy after oral application of fluorescein, rather than intravenous fluorescein angiography. The patients drank 10-20 ml 10% fluorescein sodium in 250 ml orange juice. Ophthalmoscopy was performed 30-45 minutes later using an exciter filter. Twenty-five patients with a tentative clinical diagnosis of cystoid macular edema were examined in this way. In six of them a manifest edema was detected. The results were confirmed by intravenous fluorescein angiography.

  8. Late Closure of a Stage III Idiopathic Macular Hole after Pars Plana Vitrectomy

    PubMed Central

    Afrashi, Filiz; Öztaş, Zafer; Nalçacı, Serhad

    2015-01-01

    A 57-year-old female presented to our hospital with decreased vision in her right eye. Detailed ocular examination was performed, and a macular hole was detected in the right eye. The presence of a full-thickness stage III macular hole was confirmed with optical coherence tomography (OCT) imaging. Pars plana vitrectomy followed by long-acting gas tamponade (C3F8) was performed as treatment. One month after surgery, clinical examination revealed a persistent macular hole, confirmed by an OCT scan. Although the patient was scheduled for reoperation, the surgery was postponed due to personal reasons of the patient. Surprisingly, after five months, a closure pattern with accompanying epiretinal membrane was observed in the macular hole area. The closure of the macular hole was completed without any further intervention 8 months post-surgery. In cases of unclosed macular hole after the first surgery, if a second surgery cannot be performed, follow-up with OCT recommended due to the possibility of spontaneous closure. However, spontaneous closure of a persistent macular hole following PPV is rare, so early diagnosis and surgical repair of unclosed macular holes must remain the primary goal. PMID:27800248

  9. [Literature review: Diabetic macular edema. Repercussions and treatment].

    PubMed

    Carmona-Moxica, Luis Roberto; Hernández-Núñez, Fabiola

    2015-01-01

    In our country there is a report of prevalence of Diabetes Mellitus in the adult population of a 10%, occupying one of the first causes of morbidity-mortality, also visual and labor incapacity. Macular edema is the first cause of lost vision in the diabetic patient. There are classic methods to detect it, as the examination with biomicroscope, indirect ophthalmoscopy, fluorangiography (FAR), and the new and gold standard method for diagnostic and sequence examination, Ocular Coherence Tomography (OCT). With OCT had been possible the study of distinct types of macular edema, that could represent distinct clinical states, with specific treatments. The protocol of treatment of macular edema, continues changing. The traditional methods as metabolic control and fotocoagulation with Laser now have more options as intravitreal injection of triamcinolone, or antiangiogenic substances, even surgical treatment with vitrectomy. There are many prospective and randomized studies evaluating this methods, so until now is difficult to determine which treatment is the best.

  10. Bilateral choroidal excavation in best vitelliform macular dystrophy.

    PubMed

    Parodi, Maurizio Battaglia; Zucchiatti, Ilaria; Fasce, Francesco; Bandello, Francesco

    2014-02-14

    Focal choroidal excavation (FCE) has recently been described as one or more localized areas of choroidal excavation on spectral-domain optical coherence tomography (SD-OCT). The authors describe a case of bilateral FCE in Best vitelliform macular dystrophy (VMD). SD-OCT revealed FCE in both eyes characterized by interruption of the internal segment-outer segment junction and the presence of subretinal hyporeflective space. This is the first report describing bilateral FCE in a distinct macular disorder and specifically with VMD. Future investigations are warranted to ascertain the involvement of other macular dystrophies with atrophic evolution and the impact of FCE on the clinical course. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:e8-e10.].

  11. Nutritional modulation of age-related macular degeneration

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly worldwide. It affects 30-50 million individuals and clinical hallmarks of AMD are observed in at least one third of persons over the age of 75 in industrialized countries (Gehrs et al., 2006). Costs associated wi...

  12. Idiopathic eruptive macular pigmentation: report on two cases.

    PubMed

    Grover, Sanjiv; Basu, Atoshi

    2010-01-01

    Idiopathic eruptive macular pigmentation (IEMP) is a rather under-reported condition of unknown etiology. Clinically consisting of benign hyperpigmented macules, the condition is characterized histopathologically by dermal melanization. It must be differentiated from lichen planus pigmentosus, erythema dyschromicum perstans, fixed drug eruption and mastocytosis.

  13. IDIOPATHIC ERUPTIVE MACULAR PIGMENTATION: REPORT ON TWO CASES

    PubMed Central

    Grover, Sanjiv; Basu, Atoshi

    2010-01-01

    Idiopathic eruptive macular pigmentation (IEMP) is a rather under-reported condition of unknown etiology. Clinically consisting of benign hyperpigmented macules, the condition is characterized histopathologically by dermal melanization. It must be differentiated from lichen planus pigmentosus, erythema dyschromicum perstans, fixed drug eruption and mastocytosis. PMID:21063525

  14. Clinical significance of Staphylococcus saprophyticus identified on blood culture in a tertiary care hospital.

    PubMed

    Choi, Sang-Ho; Woo, Jun Hee; Jeong, Jin-Yong; Kim, Nam Joong; Kim, Mi-Na; Kim, Yang Soo; Ryu, Jiso

    2006-11-01

    Staphylococcus saprophyticus is a well-known cause of acute uncomplicated urinary tract infection in young women. However, the clinical significance of this organism isolated from blood culture has not been determined. We assessed the clinical significance and characteristics of S. saprophyticus identified on blood culture. A total of 24 patients were identified, and 7 patients (29.2%) were considered to have clinically significant bacteremia. Of the 7 patients with clinically significant bacteremia, hematologic malignancy was the most common underlying illness (5 patients), and tunneled-central venous catheter was the most common portal of entry (4 patients). In no case did S. saprophyticus bacteremia originate from the urinary tract. One patient died during hospitalization. However, the death was not directly related to bacteremia. In conclusion, our data suggest that bacteremia caused by S. saprophyticus is most commonly associated with tunneled-central venous catheter in patients with hematologic malignancies and may be associated with a lower risk of mortality.

  15. Topical bromfenac for prevention and treatment of cystoid macular edema following cataract surgery: a review

    PubMed Central

    Sheppard, John D

    2016-01-01

    Topical nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids, alone or in combination, have historically been used off label in the US to prevent and treat postoperative cystoid macular edema (CME). This literature review presents available data on the use of bromfenac 0.07% or 0.09% to prevent and treat CME following cataract surgery. Bromfenac is an NSAID approved to treat postoperative inflammation and reduce ocular pain following cataract surgery. Few cases of clinical CME were observed with bromfenac use in a total of 19 reviewed studies. There were no significant differences in CME incidence between bromfenac and corticosteroid-treated patients or between bromfenac- and bromfenac plus corticosteroid-treated patients. Bromfenac demonstrated comparable efficacy to other NSAIDs in preventing CME. Compared with corticosteroids, bromfenac alone or plus a corticosteroid showed similar or better efficacy in minimizing changes in retinal thickness and macular volume. In diabetic cataract surgery patients, bromfenac was comparable or superior to corticosteroids for minimizing changes in retinal thickness; also, combination therapy with bromfenac and corticosteroids may be associated with smaller changes in foveal thickness, macular thickness, and macular volume versus monotherapy with either treatment alone in this patient population. In two randomized, double-masked, placebo-controlled clinical trials with bromfenac 0.07%, CME was reported as an adverse event in 0.5% and 1.5% of patients receiving bromfenac and placebo, respectively. In an analysis of four placebo-controlled trials with bromfenac 0.09%, macular edema was reported in 0.7% and 1.4% of patients receiving bromfenac and placebo, respectively. When evaluated as treatment for acute or chronic CME, bromfenac was associated with improvement in visual acuity and reduction in retinal thickness, but few studies are available. Overall, published data suggest that bromfenac is safe and effective when

  16. A 2-Year, Phase IV, Multicentre, Observational Study of Ranibizumab 0.5 mg in Patients with Neovascular Age-Related Macular Degeneration in Routine Clinical Practice: The EPICOHORT Study.

    PubMed

    Pagliarini, Sergio; Beatty, Stephen; Lipkova, Blandina; Perez-Salvador Garcia, Eduardo; Reynders, Stefaan; Gekkieva, Margarita; Si Bouazza, Abdelkader; Pilz, Stefan

    2014-01-01

    Purpose. To assess the safety profile of ranibizumab 0.5 mg in patients with neovascular age-related macular degeneration (nAMD) in routine clinical practice. Methods. This 2-year, multicentre, observational study was conducted to capture real-world early practice and outcomes across Europe, shortly after European licensing of ranibizumab for nAMD. Being observational in nature, the study did not impose diagnostic/therapeutic interventions/visit schedule. Patients were to be treated as per the EU summary of product characteristics (SmPC) in effect during the study. Key outcome measures were incidence of selected adverse events (AEs), treatment exposure, bilateral treatment, compliance to the EU SmPC, and best-corrected visual acuity (BCVA) over 2 years. Results. 755 of 770 patients received treatment. Ranibizumab was generally well tolerated with low incidence of selected AEs (0%-1.9%). Patients received 6.2 (mean) injections and 133 patients received bilateral treatment over 2 years. Protocol deviation to treatment compliance was reported in majority of patients. The observed decline in mean BCVA (Month 12, +1.5; Month 24, -1.3 letters) may be associated with undertreatment as suggested by BCVA subgroup analysis. Conclusion. The EPICOHORT study conducted in routine clinical practice reinforces the well-established safety profile of ranibizumab in nAMD. In early European practice it appeared that the nAMD patients were undertreated.

  17. [Significance of clinical laboratory accreditation based on ISO 15189, and recent trend of international clinical laboratory accreditation program].

    PubMed

    Kawai, Tadashi

    2014-06-01

    ISO 15189 was first published in 2003, its second edition in 2007, and its third edition in 2012 by the ISO. Since 2003, through the approval of ILAC, ISO 15189 has been used for the accreditation of clinical/medical laboratories throughout the world, and approximately 5,000 clinical laboratories have now been accredited. In Japan, the JAB, in cooperation with the JCCLS, introduced the clinical laboratory accreditation program based on ISO 15189 in 2005, and 70 labs had been accredited by January 2014. It has been purely voluntary, without any governmental or regulatory involvement so far. However, it has been gradually accepted to be significant for maintaining quality management and for the improvement of clinical laboratory efficiency. The program will expand widely throughout the world in order to accomplish "one-stop testing" among clinical laboratories, at least regarding frequently-used routine laboratory tests.

  18. Macular Ganglion Cell Layer and Peripapillary Retinal Nerve Fibre Layer Thickness in Patients with Unilateral Posterior Cerebral Artery Ischaemic Lesion: An Optical Coherence Tomography Study

    PubMed Central

    Anjos, Rita; Vieira, Luisa; Costa, Livio; Vicente, André; Santos, Arnaldo; Alves, Nuno; Amado, Duarte; Ferreira, Joana; Cunha, João Paulo

    2016-01-01

    ABSTRACT The purpose of this study is to evaluate the macular ganglion cell layer (GCL) and peripapillary retinal nerve fibre layer (RNFL) thickness in patients with unilateral posterior cerebral artery (PCA) ischaemic lesions using spectral-domain optical coherence tomography (SD-OCT). A prospective, case-control study of patients with unilateral PCA lesion was conducted in the neuro-ophthalmology clinic of Centro Hospitalar Lisboa Central. Macular and peripapillary SD-OCT scans were performed in both eyes of each patient. Twelve patients with PCA lesions (stroke group) and 12 healthy normal controls were included in this study. Peripapillary RNFL comparison between both eyes of the same subject in the stroke group found a thinning in the superior-temporal (p = 0.008) and inferior-temporal (p = 0.023) sectors of the ipsilateral eye and nasal sector (p = 0.003) of the contralateral eye. Macular GCL thickness comparison showed a reduction temporally in the ipsilateral eye (p = 0.004) and nasally in the contralateral eye (p = 0.002). Peripapillary RNFL thickness was significantly reduced in both eyes of patients with PCA compared with controls, affecting all sectors in the contralateral eye and predominantly temporal sectors in the ipsilateral eye. A statistically significant decrease in macular GCL thickness was found in both hemiretinas of both eyes of stroke patients when compared with controls (p < 0.05). This study shows that TRD may play a role in the physiopathology of lesions of the posterior visual pathway. PMID:27928376

  19. Postoperative eccentric macular holes after vitrectomy and internal limiting membrane peeling.

    PubMed

    Brouzas, Dimitrios; Dettoraki, Maria; Lavaris, Anastasios; Kourvetaris, Dimitrios; Nomikarios, Nikolaos; Moschos, Marilita M

    2016-08-16

    The purpose of this study was to describe the incidence, clinical characteristics, and outcome of eccentric macular holes presenting after vitrectomy and internal limiting membrane (ILM) peeling for the treatment of macular pathology and discuss the pathogenesis of holes formation. A retrospective, noncomparative, interventional case-series study of five patients who developed eccentric macular holes postoperatively following vitrectomy in 198 consecutive patients who underwent ILM peeling for idiopathic macular hole and epiretinal membrane formation between 2008 and 2015. Five patients (2.5 %) developed full-thickness eccentric macular holes postoperatively. Three patients presented with a single eccentric macular hole, one patient had an eccentric hole after a failed idiopathic macular hole surgery and one patient developed four eccentric macular holes. The mean diameter of the holes was 584 μm (range 206-1317 μm) and the average time of holes formation after vitrectomy was 27.7 weeks (range 1-140 weeks). Postoperative best-corrected visual acuity ranged from "counting fingers" to 20/25. The eyes with the holes distant from the fovea had the best final visual acuity. No further intervention was attempted and no complications occurred. The mean follow-up time was 26.8 months. The postoperative macular holes after vitrectomy and ILM peeling were variable in number, size, and time of appearance but remained stable and were not associated with any complications. The pathogenesis of macular holes is most consistent with contraction of the residual ILM or secondary epimacular proliferation probably stimulated by ILM peeling.

  20. THE CLINICAL SIGNIFICANCE OF A POSITIVE AMNISURE TEST™ IN WOMEN WITH TERM LABOR WITH INTACT MEMBRANES

    PubMed Central

    LEE, Seung Mi; LEE, JoonHo; SEONG, Hyo Suk; LEE, Si Eun; PARK, Joong Shin; ROMERO, Roberto; YOON, Bo Hyun

    2009-01-01

    Objective The Amnisure ROM™ test is approved for the diagnosis of rupture of membranes (ROM). Yet, a fraction of patients with a positive test have intact membranes by sterile speculum examination. The objective of this study was to determine the clinical significance of this finding. Methods The study population consisted of 4 groups of nulliparous women at term: 1) not in labor without clinical evidence of ROM (n=125); 2) in labor without clinical ROM with a negative Amnisure test™ (n=56); 3) in labor without clinical ROM with a positive Amnisure test™ (n=25); and 4) in labor with clinical ROM (n=30). The Amnisure test™ was performed in cases without clinical ROM (Groups 1, 2 and 3). Results 1) The Amnisure test™ was positive more frequently in women in labor with intact membranes than in patients not in labor at term without ROM (30.9% (25/81 women) vs. 4.8% (6/125 women); p<0.001); 2) patients in labor without clinical ROM with a positive Amnisure test™ had a significantly shorter admission-to-delivery interval than those in labor without clinical ROM with a negative Amnisure test™ (p<0.05). Conclusion 1) A positive Amnisure test™ is present in about one-third nulliparous women at term presenting in labor with intact membranes; 2) Patients with a positive Amnisure test™ had a shorter admission-to-delivery interval than those with a negative test. PMID:19350444

  1. Elizabethkingia anophelis bacteremia is associated with clinically significant infections and high mortality.

    PubMed

    Lau, Susanna K P; Chow, Wang-Ngai; Foo, Chuen-Hing; Curreem, Shirly O T; Lo, George Chi-Shing; Teng, Jade L L; Chen, Jonathan H K; Ng, Ricky H Y; Wu, Alan K L; Cheung, Ingrid Y Y; Chau, Sandy K Y; Lung, David C; Lee, Rodney A; Tse, Cindy W S; Fung, Kitty S C; Que, Tak-Lun; Woo, Patrick C Y

    2016-05-17

    Unlike Elizabethkingia meningoseptica, the clinical importance of E. anophelis is poorly understood. We determined the clinical and molecular epidemiology of bacteremia caused by Elizabethkingia-like species from five regional hospitals in Hong Kong. Among 45 episodes of Elizabethkingia-like bacteremia, 21 were caused by Elizabethkingia, including 17 E. anophelis, three E. meningoseptica and one E. miricola; while 24 were caused by other diverse genera/species, as determined by 16S rRNA gene sequencing. Of the 17 cases of E. anophelis bacteremia, 15 (88%) were clinically significant. The most common diagnosis was pneumonia (n = 5), followed by catheter-related bacteremia (n = 4), neonatal meningitis (n = 3), nosocomial bacteremia (n = 2) and neutropenic fever (n = 1). E. anophelis bacteremia was commonly associated with complications and carried 23.5% mortality. In contrast, of the 24 episodes of bacteremia due to non-Elizabethkingia species, 16 (67%) were clinically insignificant. Compared to non-Elizabethkingia bacteremia, Elizabethkingia bacteremia was associated with more clinically significant infections (P < 0.01) and positive cultures from other sites (P < 0.01), less polymicrobial bacteremia (P < 0.01), and higher complication (P < 0.05) and mortality (P < 0.05) rates. Elizabethkingia bacteremia is predominantly caused by E. anophelis instead of E. meningoseptica. Elizabethkingia bacteremia, especially due to E. anophelis, carries significant morbidity and mortality, and should be considered clinically significant unless proven otherwise.

  2. Identifying Adult Dengue Patients at Low Risk for Clinically Significant Bleeding

    PubMed Central

    Wong, Joshua G. X.; Thein, Tun Linn; Leo, Yee-Sin; Pang, Junxiong; Lye, David C.

    2016-01-01

    Background Clinically significant bleeding is important for subsequent optimal case management in dengue patients, but most studies have focused on dengue severity as an outcome. Our study objective was to identify differences in admission parameters between patients who developed clinically significant bleeding and those that did not. We sought to develop a model for discriminating between these patients. Methods We conducted a retrospective study of 4,383 adults aged >18 years who were hospitalized with dengue infection at Tan Tock Seng Hospital, Singapore from 2005 to 2008. Patients were divided into those with clinically significant bleeding (n = 188), and those without (n = 4,195). Demographic, clinical, and laboratory variables on admission were compared between groups to determine factors associated with clinically significant bleeding during hospitalization. Results On admission, female gender (p<0.001); temperature >38°C (p<0.001); nausea/vomiting (p = 0.009) and abdominal pain/tenderness (p = 0.005); lower systolic blood pressure (p<0.001); higher pulse rate (p<0.001); increased absolute neutrophil count (ANC; p<0.001); reduced absolute lymphocyte count (ALC; p<0.001), haematocrit percentage (p<0.001) and platelet count (p = 0.04), and increased prothrombin time (p = 0.003) were significantly associated with clinically significant bleeding on univariate analysis. Multivariate analysis showed that independent variables in the final model were female gender (aOR 2.85; 95% CI: 1.9–4.33); temperature >38°C (aOR 1.81; 95% CI: 1.27–2.61), nausea/vomiting (aOR 1.39; 95% CI: 0.94–2.12), ANC (aOR 1.3; 95% CI: 1.15–1.46), ALC (aOR 0.4; 95% CI: 0.25–0.64), hematocrit percentage (aOR 0.96; 95% CI: 0.92–1.002) and platelet count (aOR 0.993; 95% CI: 0.988–0.998). At the cutoff of -3.919, the model achieved an AUC of 0.758 (sensitivity:0.87, specificity: 0.38, PPV: 0.06, NPV: 0.98). Conclusion Clinical risk factors associated with clinically significant

  3. Effectiveness of Telemetry Guidelines in Predicting Clinically Significant Arrhythmias in Hospitalized Patients

    PubMed Central

    Dhillon, Sandeep K.; JosephTawil; Goldstein, Baruch; Eslava-Manchego, Dayana; Singh, Jagdeep; Hanon, Sam; Schweitzer, Paul; Bergmann, Steven R.

    2012-01-01

    Background Cardiac rhythm monitoring is widely applied on hospitalized patients. However, its value has not been evaluated systematically. Methods This study considered the utility of our institutional telemetry guidelines in predicting clinically significant arrhythmias. A retrospective analysis was performed of 562 patients admitted to the telemetry unit. A total of 1932 monitoring days were evaluated. Patients were divided into 2 groups based on telemetry guidelines: “telemetry indicated” and “telemetry not indicated”. Results Differences in arrhythmia event rates and pre-defined clinical significance were determined. One hundred and forty-four (34%) vs. 16 (11%) patients had at least one arrhythmic event in the “telemetry indicated” group compared with the “telemetry not indicated” group, respectively (P = 0.001). No patient in the “telemetry not indicated” group had a clinically significant arrhythmia. In contrast, of patients in the “telemetry indicated” group who had at least one arrhythmic event, 36% were considered clinically significant (P < 0.05). Conclusion In conclusion, this study validates and supports the use of our institutional telemetry guidelines to allocate this resource appropriately and predict clinically significant arrhythmias.

  4. Bimatoprost Induced Serous Macular Detachment after Cataract Surgery

    PubMed Central

    Kaliaperumal, Subashini; Deb, Amit Kumar; Babu, K. Ramesh; Srinivasan, Renuka

    2016-01-01

    We report a case of bimatoprost induced serous macular detachment and choroidal folds following uneventful cataract surgery. A 66-year-old male using topical bimatoprost in both eyes for open angle glaucoma underwent uneventful cataract surgery in the right eye. Postoperatively, he was restarted on topical bimatoprost and antibiotic-steroids combination drops. One week after surgery, he presented with conjunctival hyperemia, serous macular detachment, and choroidal folds at the posterior pole. Fundus fluorescein angiography showed perifoveal leaks in early stage with pooling of dye in late stage. Discontinuation of bimatoprost led to resolution of serous detachment and choroidal folds within 3 weeks with significant improvement in visual acuity. Occurrence of serous macular detachment and choroidal folds in this case could be probably related to the proinflammatory property of bimatoprost. Hence, it should be used with caution in the immediate postoperative period after cataract surgery. PMID:27957367

  5. [Age related macular degeneration].

    PubMed

    Sayen, Alexandra; Hubert, Isabelle; Berrod, Jean-Paul

    2011-02-01

    Age-related macular degeneration (ARMD) is a multifactorial disease caused by a combination of genetic and environmental factors. It is the first cause of blindness in patients over 50 in the western world. The disease has been traditionally classified into early and late stages with dry (atrophic) and wet (neovascular) forms: neovascular form is characterized by new blood vessels development under the macula (choroidal neovascularisation) which lead to a rapid decline of vision associated with metamorphopsia and requiring an urgent ophtalmological examination. Optical coherence tomography is now one of the most important part of the examination for diagnosis and treatment. Patient with age related maculopathy should consider taking a dietary supplement such that used in AREDS. The treatment of the wet ARMD has largely beneficied since year 2006 of anti-VEGF (vascular endothelial growth factor) molecules such as ranibizumab or bevacizumab given as repeated intravitreal injections. A systematic follow up each 4 to 8 week in required for several years. There is no effective treatment at the moment for dry AMD. For patients with binocular visual acuity under 60/200 rehabilitation includes low vision specialist, vision aids and psychological support.

  6. What is the Clinical Significance of Cerebrospinal Fluid Biomarkers in Parkinson's disease? Is the Significance Diagnostic or Prognostic?

    PubMed

    Kim, Dana; Paik, Jin Hui; Shin, Dong-Woon; Kim, Hak-Su; Park, Chang-Shin; Kang, Ju-Hee

    2014-12-01

    The clinical diagnostic criteria of Parkinson's disease (PD) have limitations in detecting the disease at early stage and in differentiating heterogeneous clinical progression. The lack of reliable biomarker(s) for early diagnosis and prediction of prognosis is a major hurdle to achieve optimal clinical care of patients and efficient design of clinical trials for disease-modifying therapeutics. Numerous efforts to discover PD biomarkers in CSF were conducted. In this review, we describe the molecular pathogenesis of PD and discuss its implication to develop PD biomarkers in CSF. Next, we summarize the clinical utility of CSF biomarkers including alpha-synuclein for early and differential diagnosis, and prediction of PD progression. Given the heterogeneity in the clinical features of PD and none of the CSF biomarkers for an early diagnosis have been developed, research efforts to develop biomarkers to predict heterogeneous disease progression is on-going. Notably, a rapid cognitive decline followed by the development of dementia is a risk factor of poor prognosis in PD. In connection to this, CSF levels of Alzheimer's disease (AD) biomarkers have received considerable attention. However, we still need long-term longitudinal observational studies employing large cohorts to evaluate the clinical utility of CSF biomarkers reflecting Lewy body pathology and AD pathology in the brain. We believe that current research efforts including the Parkinson's Progression Markers Initiative will resolve the current needs of early diagnosis and/or prediction of disease progression using CSF biomarkers, and which will further accelerate the development of disease-modifying therapeutics and optimize the clinical management of PD patients.

  7. What is the Clinical Significance of Cerebrospinal Fluid Biomarkers in Parkinson's disease? Is the Significance Diagnostic or Prognostic?

    PubMed Central

    Kim, Dana; Paik, Jin Hui; Shin, Dong-Woon; Kim, Hak-Su; Park, Chang-Shin

    2014-01-01

    The clinical diagnostic criteria of Parkinson's disease (PD) have limitations in detecting the disease at early stage and in differentiating heterogeneous clinical progression. The lack of reliable biomarker(s) for early diagnosis and prediction of prognosis is a major hurdle to achieve optimal clinical care of patients and efficient design of clinical trials for disease-modifying therapeutics. Numerous efforts to discover PD biomarkers in CSF were conducted. In this review, we describe the molecular pathogenesis of PD and discuss its implication to develop PD biomarkers in CSF. Next, we summarize the clinical utility of CSF biomarkers including alpha-synuclein for early and differential diagnosis, and prediction of PD progression. Given the heterogeneity in the clinical features of PD and none of the CSF biomarkers for an early diagnosis have been developed, research efforts to develop biomarkers to predict heterogeneous disease progression is on-going. Notably, a rapid cognitive decline followed by the development of dementia is a risk factor of poor prognosis in PD. In connection to this, CSF levels of Alzheimer's disease (AD) biomarkers have received considerable attention. However, we still need long-term longitudinal observational studies employing large cohorts to evaluate the clinical utility of CSF biomarkers reflecting Lewy body pathology and AD pathology in the brain. We believe that current research efforts including the Parkinson's Progression Markers Initiative will resolve the current needs of early diagnosis and/or prediction of disease progression using CSF biomarkers, and which will further accelerate the development of disease-modifying therapeutics and optimize the clinical management of PD patients. PMID:25548535

  8. Macular function and morphological features in juvenile Stargardt disease: Longitudinal study

    PubMed Central

    Testa, Francesco; Melillo, Paolo; Iorio, Valentina Di; Orrico, Ada; Attanasio, Marcella; Rossi, Settimio; Simonelli, Francesca

    2014-01-01

    Purpose to evaluate disease progression in a cohort of patients with clinical and genetic diagnosis of Stargardt disease. Design longitudinal cohort study. Subjects 56 selected patients with a clinical and molecular diagnosis of Stargardt disease, an early age of onset and a median follow-up length of two years. Methods patients underwent routine examination including full-field electroretinography, microperimetry and optical coherence tomography. Main Outcome Measures best corrected visual acuity, mean retinal sensitivity, fixation stability, preferred retinal locus, inner-outer segment (IS/OS) junction loss, atrophic lesion area. Results 56 patients with a mean age of disease onset of 15.3 years (range: 3 - 28 years), a mean disease length of 12.1 years and a mean age at baseline of 27.4 years were analyzed. The median best corrected visual acuity was 20/200 in both eyes. Optical coherence tomography parameters (IS/OS alteration and retinal pigment epithelium lesion area) were obtained in 49 patients because signal quality was poor in the remaining 7 patients. Optical coherence tomography revealed a mean retinal pigment epithelium lesion area of 2.6 mm2, preserved foveal IS/OS in 4.1% of patients, loss of foveal IS/OS in 59.2%, and extensive loss of macular IS/OS in 36.7%. Microperimetric findings showed a reduced macular sensitivity (mean 10 dB) and an unstable fixation in half of the patient cohort. The longitudinal analysis showed a significant progressive reduction of best corrected visual acuity and macular sensitivity (at an estimated rate of 0.04 decimals and 1.19 dB per year, respectively) associated with a significant enlargement of retinal pigment epithelium lesion area (0.282 mm2 per year). No significant changes in ophthalmoscopic findings and electroretinographic responses were detected. Conclusions this study highlights the importance of microperimetry and optical coherence tomography in monitoring Stargardt patients. In fact, quantifying the

  9. [Age-related macular degeneration (AMD)].

    PubMed

    Michels, Stephan; Kurz-Levin, Malaika

    2009-03-01

    Today age-related macular degeneration (AMD) is the most frequent cause for legal blindness in western industrialized countries. The prevalence of this disease rises with increasing age. A multifactorial pathogenesis of AMD is postulated including genetic predisposition and environmental risk factors. The most relevant modifiable risk factor is smoking. Up to today there is no cure of this chronic disease. Prophylaxis, including a healthy diet and antioxidants as nutrional supplements for selected patients, aims to slow down the disease progression. Significant progress has been made in the treatment of the neovascular form of the disease using inhibitors of the vascular endothelial growth factor (VEGF).

  10. Comparison of Cysts in Red and Green Images for Diabetic Macular Edema

    PubMed Central

    Alhamami, Mastour A.; Elsner, Ann E.; Malinovsky, Victor E.; Clark, Christopher A.; Haggerty, Bryan P.; Ozawa, Glen Y.; Cuadros, Jorge A.; Baskaran, Karthikeyan; Gast, Thomas J.; Litvin, Taras V.; Muller, Matthew S.; Brahm, Shane G.; Young, Stuart B.; Miura, Masahiro

    2017-01-01

    ABSTRACT Purpose To investigate whether cysts in diabetic macular edema are better visualized in the red channel of color fundus camera images, as compared with the green channel, because color fundus camera screening methods that emphasize short-wavelength light may miss cysts in patients with dark fundi or changes to outer blood retinal barrier. Methods Fundus images for diabetic retinopathy photoscreening were acquired for a study with Aeon Imaging, EyePACS, University of California Berkeley, and Indiana University. There were 2047 underserved, adult diabetic patients, of whom over 90% self-identified as a racial/ethnic identify other than non-Hispanic white. Color fundus images at nominally 45 degrees were acquired with a Canon Cr-DGi non-mydriatic camera (Tokyo, Japan) then graded by an EyePACS certified grader. From the 148 patients graded to have clinically significant macular edema by the presence of hard exudates in the central 1500 μm of the fovea, we evaluated macular cysts in 13 patients with cystoid macular edema. Age ranged from 33 to 68 years. Color fundus images were split into red, green, and blue channels with custom Matlab software (Mathworks, Natick, MA). The diameter of a cyst or confluent cysts was quantified in the red-channel and green-channel images separately. Results Cyst identification gave complete agreement between red-channel images and the standard full-color images. This was not the case for green-channel images, which did not expose cysts visible with standard full-color images in five cases, who had dark fundi. Cysts appeared more numerous and covered a larger area in the red channel (733 ± 604 μm) than in the green channel (349 ± 433 μm, P < .006). Conclusions Cysts may be underdetected with the present fundus camera methods, particularly when short-wavelength light is emphasized or in patients with dark fundi. Longer wavelength techniques may improve the detection of cysts and provide more information concerning the early

  11. Bilateral macular cysts following electric burn.

    PubMed

    Sony, Parul; Venkatesh, Pradeep; Tewari, Hem Kumar; Garg, Sat Pal

    2005-02-01

    A 28-year-old man presented with bilateral acute loss of vision following a high-voltage injury. The visual acuity was 6/36 in the right eye and 6/24 in the left eye. Fundus examination revealed a well-defined round lesion simulating a full thickness macular hole in the right eye and yellow deposits in the macular area in the left eye. Optical coherence tomography (OCT) showed bilateral macular cysts, with intact outer and inner retinal layers. At 1 month follow up, OCT showed a persistent macular cyst in the right eye with spontaneous resolution of the macular cyst along with visual improvement in the left eye.

  12. Use of antivascular endothelial growth factor for diabetic macular edema

    PubMed Central

    Karim, Rushmia; Tang, Benjamin

    2010-01-01

    Background Diabetic macular edema (DME) is one of the manifestations of diabetic retinopathy leading to loss of central vision and visual acuity. It manifests itself with swelling around the central part of the retina, the area responsible for sharp vision. Current treatment includes laser therapy and intravitreal steroids with preventative measures including diabetes control. No one treatment has guaranteed control of diabetic macular edema which leads to deteriorating visual acuity, function and quality of life in patients. Vascular endothelial growth factor (VEGF) has been shown to be a critical stimulus in the pathogenesis of macular edema secondary to diabetes.1 Antiangiogenic therapy encompassed treatment with anti-VEGF which inhibits VEGF-driven neovascularization hence macular edema leading to decreased visual acuity. Objective For this review, we evaluated the effectiveness of intravitreal anti-VEGF in treating DME. Data sources We identified five trials (n = 525) using electronic databases (Cochrane Central Register of Controlled Trials [Central], Medline®, and Excerpta Medica Database [EMBASE®]) in October 2008, supplemented by hand searching of reference lists, review articles, and conference abstracts. Methods We included all randomized clinical trials (RCTs) evaluating any form of intravitreal anti-VEGF for treating DME. The main outcome factor was change in best-corrected visual acuity and central macular thickness. One author assessed eligibility, methodological quality, and extracted data. Meta analysis was performed when appropriate. Results We included three trials of adequate methodological quality in our meta-analysis. Patients treated with anti-VEGF showed improvement in visual acuity of −0.17 (95% confidence interval [CI]: −0.23, −0.10) and central macular thickness −84.69 (95% CI: −117.09, −52.30). Patients treated with combined anti-VEGF and intravitreal triamcinolone showed improvement of visual acuity of −0.19 (95% CI:

  13. Towards a model to predict macular dichromats' naming errors: effects of CIE saturation and dichromatism type.

    PubMed

    Lillo, J; Vitini, I; Caballero, A; Moreira, H

    2001-05-01

    Thirty macular dichromat children (12 protanopes + 18 deuteranopes) and 29 controls, between 5 and 9 years old, participated in a monolexemic denomination task. Their clinical status was determined after a repeated application of a chromatic test set (Ishihara, CUCVT, and TIDA). The stimuli to be named were 12 tiles from the Color-Aid set belonging to the green, blue, and purple basic categories. Results showed that: (a) Dichromats made more naming errors when low saturation stimuli were used; (b) protanopes made more errors that deuteranopes; and (c) pseudoisochromatic lines predicted accurately the type of most frequent naming errors but they underestimated macular dichromats' functional capacity to name colors. Results are consistent with a model of macular dichromats' vision that hypothesizes a residual third type of cone in the periphery of the retina. Implications of this fact for everyday use of colors by macular dichromats' and for the validity of standard clinical diagnoses are discussed.

  14. Evaluating research for clinical significance: using critically appraised topics to enhance evidence-based neuropsychology.

    PubMed

    Bowden, Stephen C; Harrison, Elise J; Loring, David W

    2014-01-01

    Meehl's (1973, Psychodiagnosis: Selected papers. Minneapolis: University of Minnesota Press) distinction between statistical and clinical significance holds special relevance for evidence-based neuropsychological practice. Meehl argued that despite attaining statistical significance, many published findings have limited practical value since they do not inform clinical care. In the context of an ever expanding clinical research literature, accessible methods to evaluate clinical impact are needed. The method of Critically Appraised Topics (Straus, Richardson, Glasziou, & Haynes, 2011, Evidence-based medicine: How to practice and teach EBM (4th ed.). Edinburgh: Elsevier Churchill-Livingstone) was developed to provide clinicians with a "toolkit" to facilitate implementation of evidence-based practice. We illustrate the Critically Appraised Topics method using a dementia screening example. We argue that the skills practiced through critical appraisal provide clinicians with methods to: (1) evaluate the clinical relevance of new or unfamiliar research findings with a focus on patient benefit, (2) help focus of research quality, and (3) incorporate evaluation of clinical impact into educational and professional development activities.

  15. Diabetic macular edema.

    PubMed

    Stefánsson, Einar

    2009-07-01

    A variety of treatment options are available for the treatment of diabetic macular edema. They include laser photocoagulation, anti-VEGF drugs, intravitreal steroids, and vitrectomy with or without release of vitreoretinal traction. A full understanding of the physiological mechanisms of these treatment modalities allows sensible combination of treatment options. Retinal photocoagulation has repeatedly been shown to improve retinal oxygenation, as does vitrectomy. Oxygen naturally reduces VEGF production and thereby decreases leakage of plasma proteins from capillaries into the tissue. In addition, vitrectomy allows faster clearance of cytokines, such as VEGF, from the retina into the vitreous cavity. The VEGF-lowering effect of photocoagulation and vitrectomy can be augmented with anti-VEGF drugs and corticosteroids reduce the effect of VEGF on capillary permeability. Starling's law explains vasogenic edema, which is controlled by osmotic and hydrostatic gradients between vessel and tissue. It explains how VEGF-induced vascular permeability causes plasma protein to leak into the tissue interstitial space, thus decreasing the osmotic pressure gradient between vessel and tissue, resulting in water accumulation, i.e. edema. This is reversed by reducing VEGF production, which is achieved with laser treatment; or by removing VEGF with antibodies or vitrectomy; or by reducing the permeability effect with steroids. At the same time, Starling's law takes into account hemodynamic changes that affect the hydrostatic gradient. High arterial blood pressure and hypoxic vasodilatation increase the hydrostatic pressure in the microcirculation, which increases water flux from vessel to tissue and induce edema. Treatment of arterial hypertension or reversal of retinal hypoxia with laser reverses this pathophysiology and reduces edema. Newton's third law explains, that vitreoretinal traction decreases hydrostatic tissue pressure in the retina, increases the pressure gradient

  16. The Functional Significance of Affect Recognition, Neurocognition, and Clinical Symptoms in Schizophrenia

    PubMed Central

    Hsiao, Sigmund

    2017-01-01

    Objectives The complex relationship and exact extent of the contribution of plausible indictors to social functional outcome in schizophrenia remain unclear. The present study aimed to explore the functional significance of clinical symptoms, neurocognition, and affect recognition simultaneously in schizophrenia. Methods The clinical symptoms, basic neurocognition, facial emotion recognition, and social functioning of 154 subjects, including 74 with schizophrenia and 80 nonclinical comparisons, were assessed. Results We observed that various subdomains of social functioning were extensively related to general intelligence, basic neurocognition, facial emotion recognition, and clinical symptoms, with different association patterns. Multivariate regression analyses revealed that years of education, age, sustained attention, working memory, and facial emotion recognition were significantly associated with global social functioning in schizophrenia. Conclusion Our findings suggest that affect recognition combined with nonsocial neurocognition demonstrated a crucial role in predicting global social function in schizophrenia. PMID:28099444

  17. Clinically Significant Change to Establish Benchmarks in Residential Drug and Alcohol Treatment Services

    ERIC Educational Resources Information Center

    Billingham, Daniel D.; Kelly, Peter J.; Deane, Frank P.; Crowe, Trevor P.; Buckingham, Mark S.; Craig, Fiona L.

    2012-01-01

    There is increasing emphasis on the use routine outcome assessment measures to inform quality assurance initiatives. The calculation of reliable and clinically significant change indices is one strategy that organizations could use to develop both internal and externally focused benchmarking processes. The current study aimed to develop reliable…

  18. Reliability and Clinical Significance of Mobility and Balance Assessments in Multiple Sclerosis

    ERIC Educational Resources Information Center

    Learmonth, Yvonne C.; Paul, Lorna; McFadyen, Angus K.; Mattison, Paul; Miller, Linda

    2012-01-01

    The aim of the study was to establish the test-retest reliability, clinical significance and precision of four mobility and balance measures--the Timed 25-Foot Walk, Six-minute Walk, Timed Up and Go and the Berg Balance Scale--in individuals moderately affected by multiple sclerosis. Twenty four participants with multiple sclerosis (Extended…

  19. Investigation of Clinically Significant Change by Severity Level in College Counseling Center Clients

    ERIC Educational Resources Information Center

    Wolgast, Brad M.; Rader, Jill; Roche, Deborah; Thompson, C. Patricia; von Zuben, F. Christian; Goldberg, Allan

    2005-01-01

    The authors investigated the number of sessions necessary for college counseling center clients of different levels of severity of distress at intake to achieve clinically significant change (CS) in therapy. The Outcome Questionnaire-45 (M. J. Lambert, N. B. Hansen, et al., 1996) was used to categorize 914 clients by severity of distress. Analyses…

  20. Risk Factors for Clinically Significant Intimate Partner Violence among Active-Duty Members

    ERIC Educational Resources Information Center

    Smith Slep, Amy M.; Foran, Heather M.; Heyman, Richard E.; Snarr, Jeffery D.

    2011-01-01

    Hypothesized risk factors for men's and women's clinically significant intimate partner violence (CS-IPV) from four ecological levels (i.e., individual, family, workplace, community) were tested in a representative sample of active-duty U.S. Air Force members (N = 42,744). When considered together, we expected only individual and family factors to…

  1. Elizabethkingia anophelis bacteremia is associated with clinically significant infections and high mortality

    PubMed Central

    Lau, Susanna K. P.; Chow, Wang-Ngai; Foo, Chuen-Hing; Curreem, Shirly O. T.; Lo, George Chi-Shing; Teng, Jade L. L.; Chen, Jonathan H. K.; Ng, Ricky H. Y.; Wu, Alan K. L.; Cheung, Ingrid Y. Y.; Chau, Sandy K. Y.; Lung, David C.; Lee, Rodney A.; Tse, Cindy W. S.; Fung, Kitty S. C.; Que, Tak-Lun; Woo, Patrick C. Y.

    2016-01-01

    Unlike Elizabethkingia meningoseptica, the clinical importance of E. anophelis is poorly understood. We determined the clinical and molecular epidemiology of bacteremia caused by Elizabethkingia-like species from five regional hospitals in Hong Kong. Among 45 episodes of Elizabethkingia-like bacteremia, 21 were caused by Elizabethkingia, including 17 E. anophelis, three E. meningoseptica and one E. miricola; while 24 were caused by other diverse genera/species, as determined by 16S rRNA gene sequencing. Of the 17 cases of E. anophelis bacteremia, 15 (88%) were clinically significant. The most common diagnosis was pneumonia (n = 5), followed by catheter-related bacteremia (n = 4), neonatal meningitis (n = 3), nosocomial bacteremia (n = 2) and neutropenic fever (n = 1). E. anophelis bacteremia was commonly associated with complications and carried 23.5% mortality. In contrast, of the 24 episodes of bacteremia due to non-Elizabethkingia species, 16 (67%) were clinically insignificant. Compared to non-Elizabethkingia bacteremia, Elizabethkingia bacteremia was associated with more clinically significant infections (P < 0.01) and positive cultures from other sites (P < 0.01), less polymicrobial bacteremia (P < 0.01), and higher complication (P < 0.05) and mortality (P < 0.05) rates. Elizabethkingia bacteremia is predominantly caused by E. anophelis instead of E. meningoseptica. Elizabethkingia bacteremia, especially due to E. anophelis, carries significant morbidity and mortality, and should be considered clinically significant unless proven otherwise. PMID:27185741

  2. Clinical significance of GLUT-1 expression in patients with esophageal cancer treated with concurrent chemoradiotherapy.

    PubMed

    Chiba, Itaru; Ogawa, Kazuhiko; Morioka, Takamitsu; Shimoji, Hideaki; Sunagawa, Nao; Iraha, Shiro; Nishimaki, Tadashi; Yoshimi, Naomi; Murayama, Sadayuki

    2011-01-01

    This study aimed to investigate whether glucose transporter-1 (GLUT-1) expression in a pretreatment esophageal cancer biopsy was predictive of clinical outcomes in patients with esophageal cancer undergoing concurrent chemoradiotherapy (CRT). A total of 25 patients with esophageal cancer treated with concurrent CRT were reviewed. Radiotherapy was administered up to total doses of 40-66.6 Gy (median 66.6 Gy) with a single fraction of 1.8-2 Gy. Regarding chemotherapy, cisplatin (80 mg/m(2) on day 1) and 5-fluorouracil (800 mg/m(2) on days 2-6) were used concurrently with radiotherapy, every 3-4 weeks for a total of 1-2 courses. Tissue samples from esophageal carcinoma were obtained from the 25 patients by biopsy prior to concurrent CRT, and a semiquantitative analysis of GLUT-1 expression was performed using immunohistochemical staining. High GLUT-1 expression was observed in 7 of 25 (28%) patients, and GLUT-1 expression was significantly correlated with clinical T stage (p=0.0454), clinical N stage (p=0.0324) and initial response to CRT (p=0.0185). Patients with a high GLUT-1 expression had significantly poorer local control (LC) (5-year LC 28.6%) than those with a low expression (5-year LC 73.4%, p<005). Multivariate analysis revealed that GLUT-1 and the number of chemotherapy courses were independent prognostic factors for LC. Patients with a high GLUT-1 expression had significantly lower recurrence-free survival (RFS) compared to those with a low GLUT-1 expression (p=0.0405). Multivariate analysis revealed that GLUT-1, the number of chemotherapy courses and clinical M stage were independent prognostic factors for RFS. GLUT-1 expression was significantly correlated with clinical T stage, clinical N stage and initial response to concurrent CRT, and was predictive of LC and RFS for patients with esophageal cancer treated with concurrent CRT.

  3. Evaluation of Macular Retinal Ganglion Cell-Inner Plexiform Layer Thickness after Vitrectomy with Internal Limiting Membrane Peeling for Idiopathic Macular Holes

    PubMed Central

    Velázquez-Villoria, Álvaro; Zapata, Miguel A.; Figueroa, Marta S.; Suárez-Leoz, Marta; Arrevola, Luis; Teijeiro, María-Ángeles; García-Layana, Alfredo

    2014-01-01

    Purpose. To evaluate macular retinal ganglion cell-inner plexiform layer (GCIPL) thickness changes after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole repair using a high-resolution spectral-domain optical coherence tomography (SD-OCT). Methods. 32 eyes from 32 patients with idiopathic macular holes who underwent vitrectomy with internal limiting membrane peeling between January 2011 and July 2012 were retrospectively analyzed. GCIPL thickness was measured before surgery, and at one month and at six months after surgery. Values obtained from automated and semimanual SD-OCT segmentation analysis were compared (Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, CA). Results. No significant differences were found between average GCIPL thickness values between preoperative and postoperative analysis. However, statistical significant differences were found in GCIPL thickness at the temporal macular quadrants at six months after surgery. Quality measurement analysis performed by automated segmentation revealed a significant number of segmentation errors. Semimanual segmentation slightly improved the quality of the results. Conclusion. SD-OCT analysis of GCIPL thickness found a significant reduction at the temporal macular quadrants at 6 months after Brilliant Blue G-assisted internal limiting membrane peeling for idiopathic macular hole. PMID:25110679

  4. Fundus Autofluorescence in Age-related Macular Degeneration

    PubMed Central

    Ly, Angelica; Nivison-Smith, Lisa; Assaad, Nagi; Kalloniatis, Michael

    2017-01-01

    ABSTRACT Fundus autofluorescence (FAF) provides detailed insight into the health of the retinal pigment epithelium (RPE). This is highly valuable in age-related macular degeneration (AMD) as RPE damage is a hallmark of the disease. The purpose of this paper is to critically appraise current clinical descriptions regarding the appearance of AMD using FAF and to integrate these findings into a chair-side reference. A wide variety of FAF patterns have been described in AMD, which is consistent with the clinical heterogeneity of the disease. In particular, FAF imaging in early to intermediate AMD has the capacity to reveal RPE alterations in areas that appear normal on funduscopy, which aids in the stratification of cases and may have visually significant prognostic implications. It can assist in differential diagnoses and also represents a reliable, sensitive method for distinguishing reticular pseudodrusen. FAF is especially valuable in the detection, evaluation, and monitoring of geographic atrophy and has been used as an endpoint in clinical trials. In neovascular AMD, FAF reveals distinct patterns of classic choroidal neovascularization noninvasively and may be especially useful for determining which eyes are likely to benefit from therapeutic intervention. FAF represents a rapid, effective, noninvasive imaging method that has been underutilized, and incorporation into the routine assessment of AMD cases should be considered. However, the practicing clinician should also be aware of the limitations of the modality, such as in the detection of foveal involvement and in the distinction of phenotypes (hypo-autofluorescent drusen from small areas of geographic atrophy). PMID:27668639

  5. Group cognitive behavioural treatment of youth anxiety in community based clinical practice: Clinical significance and benchmarking against efficacy.

    PubMed

    Jónsson, H; Thastum, M; Arendt, K; Juul-Sørensen, M

    2015-10-01

    The efficacy of a group cognitive behavioural therapy (CBT) programme (Cool Kids) of youth anxiety has been demonstrated at university clinics in Australia and Denmark and similar CBT programmes have been found effective within community settings in other countries. However, most effectiveness studies of CBT for youth anxiety have either used a mixture of CBT guidelines, or translated protocols not previous tested in an efficacy trial. This study used a benchmarking strategy to compare outcomes from the same CBT programme used at a university research clinic (N=87) and community centres (N=82). There was a significant reduction on both clinical and self-report measures of youth anxiety over time with medium to large effect sizes within both samples. Treatment effects on self-report measures of youth anxiety were significantly larger within the university sample, while changes in clinical measures of youth anxiety were similar in the two samples. Overall these findings suggest that an efficacious CBT group treatment programme developed within research contexts is transportable to community centres. Despite being effective within the community, the results indicate that the treatment may lose some of its efficacy when disseminated to the community.

  6. Electrophysiological changes after 360° retinotomy and macular translocation for subfoveal choroidal neovascularisation in age related macular degeneration

    PubMed Central

    Luke, C.; Aisenbrey, S.; Luke, M.; Marzella, G.; Bartz-Schmidt, K. U.; Walter, P.

    2001-01-01

    AIM—To evaluate electrophysiological changes after 360° retinotomy and macular translocation for subfoveal choroidal neovascularisation in patients with age related macular degeneration (AMD).
METHODS—A consecutive series of 32 patients suffering from subfoveal choroidal neovascularisation secondary to AMD underwent 360° retinotomy and macular translocation. The ERG served as the main parameter of the study and was recorded 1 day before the translocation surgery and no earlier than 4 weeks after the silicone oil removal.
RESULTS—The scotopic ERG amplitudes were significantly reduced after translocation surgery. Depending on the applied flash luminance the mean b-wave amplitude reduction of the scotopic ERG varied between 67% (0.2 cd.s/m2) and 74% (0.03 cd.s/m2). The a-waves and b-waves of the saturating light response decreased significantly by 46% and 59%, respectively. The photopic a-wave and b-wave amplitudes were significantly lower after the translocation surgery resulting in a mean reduction of 27% and 43%, respectively.
CONCLUSIONS—Although macular translocation may provide the potential of preserving and even restoring vision in patients with subfoveal choroidal neovascular membranes secondary to AMD the present study indicates that a significant electrophysiological decrease is caused by surgical procedures associated with this technique. Further research is necessary to clarify if certain modifications of the surgical procedure are able to substantially reduce the neuroretinal trauma.

 PMID:11466247

  7. Technology needs for tomorrow's treatment and diagnosis of macular diseases

    NASA Astrophysics Data System (ADS)

    Soubrane, Gisèle

    2008-02-01

    Retinal imaging is the basis of macular disease's diagnosis. Currently available technologies in clinical practice are fluorescein and indocyanin green (ICG) angiographies, in addition to optical coherence tomography (OCT), which is an in vivo "histology-like" cross-sectional images of the retina. Recent developments in the field of OCT imaging include Spectral-Domain OCT. However OCT remains a static view of the macula with no direct link with dynamic observation obtained by angiographies. Adaptative optics is an encouraging perspective for fundus analysis in the future, and could be linked to OCT or angiographies. Treatments of macular disease have exploded these past few years. Pharmacologic inhibition of angiogenesis represents a novel approach in the treatment of choroidal neovascularization in eyes with age-related macular degeneration. The major action explored is the direct inhibition of the protein VEGF with antibody-like products. New anti-VEGF drugs are in development aiming at the VEGF receptors or synthesis of VEGF. But various components of the neovascular cascade, including growth factor expression, extracellular matrix modulation, integrin inhibition represent potential targets for modulation with drugs. Intra-vitreal injections are nowadays the main route of administration for these new treatments but they are potentially responsible of side effects such as endophtalmitis. Development of other routes of treatment would require new formulation of used drugs. The improvement of retinal imaging leads to a better understanding of macular disease mechanisms and will help to develop new routes and targets of treatment.

  8. Uveitic Macular Edema: Treatment Update

    PubMed Central

    Goldhardt, Raquel; Rosen, Bradley Simon

    2016-01-01

    The aim of this review is to summarize recent developments in the treatment of uveitic macular edema (ME). ME represent a major cause of visual loss in uveitis and adequate management is crucial for the maintenance of useful vision in patients with chronic uveitis. PMID:27347446

  9. Age-Related Macular Degeneration.

    PubMed

    Mehta, Sonia

    2015-09-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss in the elderly. AMD is diagnosed based on characteristic retinal findings in individuals older than 50. Early detection and treatment are critical in increasing the likelihood of retaining good and functional vision.

  10. Osteonectin-expressing cells in human stomach cancer and their possible clinical significance.

    PubMed

    Maeng, Hack-Young; Song, Seok Bean; Choi, Dong-Kug; Kim, Kyoon Eon; Jeong, Hyun Young; Sakaki, Yoshiyuki; Furihata, Chie

    2002-10-08

    The clinical significance of osteonectin in human stomach cancer was examined immunohistochemically and molecular biologically in 31 differentiated and eight undifferentiated stomach adenocarcinomas and 19 non-cancer stomach tissues. Osteonectin-mAb-stained cells were observed in stroma of 90% differentiated and 63% undifferentiated adenocarcinomas, and of 26% non-cancer stomach tissues. Competitive reverse transcriptase polymerase chain reaction results generally coincided with immunohistochemical data. The present results suggest that osteonectin is highly expressed in reactive stroma associated with invasive differentiated adenocarcinomas and that it may serve as a useful clinical diagnostic marker for stomach cancer.

  11. [SIRS (systemic inflammatory response syndrome): clinical entity, definitions, and the significance].

    PubMed

    Kushimoto, S; Yamamoto, Y

    1999-01-01

    The clinical entity, definitions, and the significance of SIRS (systemic inflammatory response syndrome) were reviewed. The term, SIRS was proposed to define sepsis and its sequelae clearly in 1991, in order to make early detection of the disease possible, and to improve the ability to compare innovative potential diagnostic and therapeutic modalities by standardizing terms. Although the criteria of SIRS is not strict and too sensitive, SIRS has been shown to be useful as a warning sign of severe condition in clinical setting. We also discussed about a new concept, CARS (compensatory anti-inflammatory response syndrome), which was characterized as anti-inflammatory mediators-dominant condition, in this issue.

  12. Mechanisms and clinical significance of early recurrences of atrial arrhythmias after catheter ablation for atrial fibrillation

    PubMed Central

    Liang, Jackson J; Dixit, Sanjay; Santangeli, Pasquale

    2016-01-01

    Early recurrence of atrial arrhythmias (ERAA) after ablation is common and strongly predicts late recurrences and ablation failure. However, since arrhythmia may eventually resolve in up to half of patients with ERAA, guidelines do not recommend immediate reintervention for ERAA episodes occurring during a 3-mo post-ablation blanking period. Certain clinical demographic, electrophysiologic, procedural, and ERAA-related characteristics may predict a higher likelihood of long-term ablation failure. In this review, we aim to discuss potential mechanisms of ERAA, and to summarize the clinical significance, prognostic implications, and treatment options for ERAA. PMID:27957250

  13. Structure tensor based automated detection of macular edema and central serous retinopathy using optical coherence tomography images.

    PubMed

    Hassan, Bilal; Raja, Gulistan; Hassan, Taimur; Usman Akram, M

    2016-04-01

    Macular edema (ME) and central serous retinopathy (CSR) are two macular diseases that affect the central vision of a person if they are left untreated. Optical coherence tomography (OCT) imaging is the latest eye examination technique that shows a cross-sectional region of the retinal layers and that can be used to detect many retinal disorders in an early stage. Many researchers have done clinical studies on ME and CSR and reported significant findings in macular OCT scans. However, this paper proposes an automated method for the classification of ME and CSR from OCT images using a support vector machine (SVM) classifier. Five distinct features (three based on the thickness profiles of the sub-retinal layers and two based on cyst fluids within the sub-retinal layers) are extracted from 30 labeled images (10 ME, 10 CSR, and 10 healthy), and SVM is trained on these. We applied our proposed algorithm on 90 time-domain OCT (TD-OCT) images (30 ME, 30 CSR, 30 healthy) of 73 patients. Our algorithm correctly classified 88 out of 90 subjects with accuracy, sensitivity, and specificity of 97.77%, 100%, and 93.33%, respectively.

  14. Covering all clinically significant areas of the colon surface in virtual colonoscopy

    NASA Astrophysics Data System (ADS)

    Kreeger, Kevin; Dachille, Frank; Wax, Mark R.; Kaufman, Arie E.

    2002-04-01

    We have developed a method that automatically displays, places in sized order and allows viewing of the areas of the colon surface not visualized during initial endoscopic navigational viewing. While complete surface visualization is possible, we demonstrate that all of these missed patches do not have to be reviewed to detect clinically significant colon polyps. CT scans are performed on 147 patients and volunteers after bowel preparation and colon distention with CO2. After automatic segmentation and electronic cleansing of the colon lumen, the medial axis (centerline) is extracted. Volume rendering fly-through along the centerline is performed and visualized surfaces are marked. To simulate optical colonoscopy, the virtual camera is passed in the antegrade direction. For virtual colonoscopy, the camera is passed both antegrade and retrograde, and the combined visible surface voxel count is recorded. After both fly-throughs, the total visualized surface is recorded and all 'patches' of connected surface area not yet seen are identified, measured, sorted by size, and counted. Clinically significant patches, defined as smallest diameter being > 5mm, are sequentially visualized by stepping through the sorted list until reaching the patch diameter of 5 mm.. for each. By enabling endoscopic navigation in both antegrade and retrograde directions, virtual colonoscopy is able to evaluate behind haustral folds and around sharp bends, thereby visualizing significantly more surface area than optical colonoscopy. Furthermore, automatic marking of the visualized surface area and identifying and viewing unseen patches allows examination of all clinically significant surfaces of the colon.

  15. Cross-reactivity of steroid hormone immunoassays: clinical significance and two-dimensional molecular similarity prediction

    PubMed Central

    2014-01-01

    Background Immunoassays are widely used in clinical laboratories for measurement of plasma/serum concentrations of steroid hormones such as cortisol and testosterone. Immunoassays can be performed on a variety of standard clinical chemistry analyzers, thus allowing even small clinical laboratories to do analysis on-site. One limitation of steroid hormone immunoassays is interference caused by compounds with structural similarity to the target steroid of the assay. Interfering molecules include structurally related endogenous compounds and their metabolites as well as drugs such as anabolic steroids and synthetic glucocorticoids. Methods Cross-reactivity of a structurally diverse set of compounds were determined for the Roche Diagnostics Elecsys assays for cortisol, dehydroepiandrosterone (DHEA) sulfate, estradiol, progesterone, and testosterone. These data were compared and contrasted to package insert data and published cross-reactivity studies for other marketed steroid hormone immunoassays. Cross-reactivity was computationally predicted using the technique of two-dimensional molecular similarity. Results The Roche Elecsys Cortisol and Testosterone II assays showed a wider range of cross-reactivity than the DHEA sulfate, Estradiol II, and Progesterone II assays. 6-Methylprednisolone and prednisolone showed high cross-reactivity for the cortisol assay, with high likelihood of clinically significant effect for patients administered these drugs. In addition, 21-deoxycortisol likely produces clinically relevant cross-reactivity for cortisol in patients with 21-hydroxylase deficiency, while 11-deoxycortisol may produce clinically relevant cross-reactivity in 11β-hydroxylase deficiency or following metyrapone challenge. Several anabolic steroids may produce clinically significant false positives on the testosterone assay, although interpretation is limited by sparse pharmacokinetic data for some of these drugs. Norethindrone therapy may impact immunoassay measurement

  16. Identifying risk factors for clinically significant diabetic macula edema in patients with type 2 diabetes mellitus.

    PubMed

    Kamoi, Kyuzi; Takeda, Keiji; Hashimoto, Kaoru; Tanaka, Reiko; Okuyama, Shinya

    2013-05-01

    It is known that clinic blood pressure (BP), gender, cigarette smoking, dyslipidemia, anemia and thiazolidenediones (TZD) treatment are predictors for clinically significant diabetic macula edema (CSDME). We examined a most risky factor for CSDME in Japanese patients with type 2 diabetes mellitus (T2DM) and diabetic retinopathy (DR) confirmed using optical coherence tomography by multiple regression analysis (MRA). As the risk factors, wakening-up BP was added to such factors. Seven diabetic Japanese patients with CSDME (group 1) and 124 subjects without CSDME (group 2) assonated with DR using optical coherence tomography were studied. The durations of T2DM in groups 1 and 2 were 15±10 years and 20±15 years, respectively. There was no statistically difference in means of gender, duration, age, body mass index (BMI), HbA1c, TC, LDL and TC/HDL, serum creatinine, urinary albumin excretion rate, and clinic BP between two groups. Morning systolic home BP (MSHBP), cigarette smoking and foveal thickness were significantly (p<0.001) higher in group 1 than group 2, whereas visual acuity was significantly (p<0.00?) lower in group 1 than in group 2. The patients in both groups had received various kinds of drugs for hyperglycemia, hypertension and others. There were no significant differences in the variables in both groups. MRA revealed that MSHBP, cigarette smoking and pioglitazone as TZD treatment were significantly positive predictors for CSDME, while BMI had a significantly negative predictor. Other variables were not significantly correlated to CSDME. The review summarizes a multiple regression analysis revealed that MSHBP makes an addition to predictive factors for CSDME among risk factors reported previously in patient with T2DM.

  17. A review of therapies for diabetic macular oedema and rationale for combination therapy

    PubMed Central

    Amoaku, W M K; Saker, S; Stewart, E A

    2015-01-01

    Diabetic macular oedema (DMO) is responsible for significant visual impairment in diabetic patients. The primary cause of DMO is fluid leakage resulting from increased vascular permeability through contributory anatomical and biochemical changes. These include endothelial cell (EC) death or dysfunction, pericyte loss or dysfunction, thickened basement membrane, loss or dysfunction of glial cells, and loss/change of EC Glycocalyx. The molecular changes include increased reactive oxygen species, pro-inflammatory changes: advanced glycation end products, intracellular adhesion molecule-1, Complement 5–9 deposition and cytokines, which result in increased paracellular permeability, tight junction disruption, and increased transcellular permeability. Laser photocoagulation has been the mainstay of treatment until recently when pharmacological treatments were introduced. The current treatments for DMO target reducing vascular leak in the macula once it has occurred, they do not attempt to treat the underlying pathology. These pharmacological treatments are aimed at antagonising vascular endothelial growth factor (VEGF) or non-VEGF inflammatory pathways, and include intravitreal injections of anti-VEGFs (ranibizumab, aflibercept or bevacizumab) or steroids (fluocinolone, dexamethasone or triamcinolone) as single therapies. The available evidence suggests that each individual treatment modality in DMO does not result in a completely dry macula in most cases. The ideal treatment for DMO should improve vision and improve morphological changes in the macular (eg, reduce macular oedema) for a significant duration, reduced adverse events, reduced treatment burden and costs, and be well tolerated by patients. This review evaluates the individual treatments available as monotherapies, and discusses the rationale and potential for combination therapy in DMO. A comprehensive review of clinical trials related to DMO and their outcomes was completed. Where phase III randomised

  18. Expression and clinical significance of Kelch-like epichlorohydrin-associated protein 1 in breast cancer.

    PubMed

    Zhang, L; Yang, W P; Wu, L Y; Zhu, X; Wei, C Y

    2016-05-12

    Our objective was to explore the expression and clinical significance of Kelch-like epichlorohydrin-associated protein 1 (Keap1) in breast cancer tissue. Eighty-one breast cancer patients having undergone surgical treatment in our hospital between March 2002 and December 2008 were enrolled in this study. Normal tissue adjacent to tumors was used for the control samples. Diagnoses for all patients were confirmed by postoperative pathological examination. Immunohistochemical assays were used to measure the expression of Keap1 protein in breast cancer tissue and adjacent normal tissue, and its clinical significance was explored. We observed that 24.6% breast cancer tissue samples were positive for Keap1, a significantly lower proportion than that seen with adjacent normal tissue specimens (80.2%; P < 0.05). The presence of Keap1 expression did not correlate with age, tumor size, pathological classification, or degree of differentiation. However, it was found to be significantly associated with tumor-node-metastasis stage and the presence of lymphatic metastasis. Kaplan-Meier survival analysis showed a remarkably higher five-year survival rate among patients with positive Keap1 expression than in those lacking detectable levels of the protein (P = 0.032). Keap1 expression is significantly decreased in breast cancer tissue; therefore, the early detection of its expression might have great significance in determining prognosis for breast cancer patients.

  19. Significance of frailty for predicting adverse clinical outcomes in different patient groups with specific medical conditions.

    PubMed

    Ritt, Martin; Gaßmann, Karl-Günter; Sieber, Cornel Christian

    2016-10-01

    Frailty is a major health burden in an aging society. It constitutes a clinical state of reduced physiological reserves that is associated with a diminished ability to withstand internal and external stressors. Frail patients have an increased risk for adverse clinical outcomes, such as mortality, readmission to hospital, institutionalization and falls. Of further clinical interest, frailty might be at least in part reversible in some patients and subject to preventive strategies. In daily clinical practice older patients with a complex health status, who are mostly frail or at least at risk of developing frailty, are frequently cared for by geriatricians. Recently, clinicians and scientists from other medical disciplines, such as cardiology, pulmonology, gastroenterology, nephrology, endocrinology, rheumatology, surgery and critical care medicine also discovered frailty to be an interesting instrument for risk stratification of patients, including younger patients. In this review we highlight the results of recent studies that demonstrated the significance of frailty to predict adverse clinical outcomes in patients with specific medical conditions, such as cardiac, lung, liver and kidney diseases as well as diabetes mellitus, osteoarthritis, trauma patients, patients undergoing surgery and critically ill patients. Multiple studies in patients with the aforementioned specific medical conditions could be identified demonstrating a predictive role of frailty for several adverse clinical outcomes. The association between frailty and adverse clinical outcomes reported in these studies was in part independent of several major potential confounder factors, such as age, sex, race, comorbidities and disabilities and were also detected in younger patients.

  20. Macular Surgery Using Intraoperative Spectral Domain Optical Coherence Tomography

    PubMed Central

    Riazi-Esfahani, Mohammad; Khademi, Mohammad Reza; Mazloumi, Mehdi; Khodabandeh, Alireza; Riazi-Esfahani, Hamid

    2015-01-01

    Purpose: To report the use of intraoperative spectral domain optical coherence tomography (SD-OCT) for detecting anatomical changes during macular surgery. Methods: In a consecutive case series, 32 eyes of 32 patients undergoing concurrent pars plana vitrectomy and intraoperative SD-OCT for macular hole (MH), epiretinal membrane (ERM) and vitreomacular traction (VMT) were enrolled. Intraoperative changes in retinal thickness and dimensions of the macular hole were measured in patients with ERM and VMT following surgical manipulation using a hand-held SD-OCT device (iVue, Optovue Inc., Fremont, CA, USA). Results: SD-OCT images of sixteen eyes with macular hole were subjected to quantitative and qualitative analysis. All MH dimensions remained stable during consecutive stages of surgery except for MH apex diameter, which showed a significant decrease after internal limiting membrane (ILM) peeling (P=0.025). Quantitative analysis of ten patients with ERM showed a significant decrease in retinal thickness after membrane removal (P=0.018) which did not remain significant until the end of the procedure (P=0.8). In three cases, subretinal fluid was formed after ILM peeling. Quantitative analysis of five patients with VMT showed a decrease in retinal thickness during consecutive steps of the surgery, although these changes were not significant. In two cases, subretinal fluid was formed after ILM peeling. Conclusion: Intraoperative SD-OCT is a useful imaging technique which provides vitreoretinal surgeons with rapid awareness of changes in macular anatomy during surgery and may therefore result in better anatomical and visual outcomes. PMID:26730318

  1. Clinical Significance of Nontuberculous Mycobacteria Isolated From Respiratory Specimens in a Chinese Tuberculosis Tertiary Care Center

    PubMed Central

    Duan, Hongfei; Han, Xiqin; Wang, Qingfeng; Wang, Jing; Wang, Jun; Chu, Naihui; Huang, Hairong

    2016-01-01

    The clinical relevance of non-tuberculous mycobacteria (NTM) has been reported to be different dramatically by species or by regions, however, no such evaluation has been performed in China.A retrospective study was performed in Beijing Chest Hospital. All the NTM strains isolated from respiratory specimens in the past 5 years, and patients’ clinical records (symptoms and radiographic information etc.) were investigated. The clinical relevance was evaluated according to the criteria recommended by the American Thoracic society. Totally 232 NTM strains were recruited, among them, M. intracellulare was the dominant species (40.5%), followed by M. abscessus (28.4%). 109 patients, with 185 total isolates, had full clinical records available for review. 84.4% (38/45), 85.7% (24/28%) and 63.6% (7/11) of patients with isolation of M. intracellulare, M. abscessus and M. kansasii, respectively, were categorized as definite NTM disease. Whereas all the 10 patients with isolation of M. gordonae were defined as unlikely NTM disease. The majority of NTMs isolates yielded from respiratory specimens in Beijing Chest Hospital were clinically significant, and M. intracellulare and M. abscessus was the dominated species of NTM lung disease. NTM lung infections demonstrated some specific chest radiograph characteristics. PMID:27808247

  2. Clinical significance of occult metastatic cells in bone marrow of breast cancer patients.

    PubMed

    Braun, S; Pantel, K

    2001-01-01

    The early and clinically occult spread of viable tumor cells to the organism is increasingly considered a hallmark in cancer progression, as emerging data suggest that these cells are precursors of subsequent distant relapse. Using monoclonal antibodies to epithelial cytokeratins or tumor-associated cell membrane glycoproteins, individual carcinoma cells can be detected on cytologic bone marrow preparations at frequencies of 10(-5) to 10(-6). Prospective clinical studies have shown that the presence of these immunostained cells in bone marrow, as a frequent site of overt metastases, is prognostically relevant with regard to relapse-free and overall survival. This screening approach may be, therefore, used to improve tumor staging and guide the stratification of patients for adjuvant therapy in clinical trials. Another promising application is monitoring the response of micrometastatic cells to adjuvant therapies, which, at present, can only be assessed retrospectively after an extended period of clinical follow-up. The present review summarizes the current data on the clinical significance of occult metastatic breast cancer cells in bone marrow.

  3. Clinical significance of molecular diagnosis for gastric cancer lymph node micrometastasis

    PubMed Central

    Sonoda, Hiromichi; Tani, Tohru

    2014-01-01

    Advances in molecular diagnostic tools have allowed the identification of lymph node micrometastasis (LNM), including isolated tumor cells, in cancer patients. While immunohistochemistry and reverse transcription-polymerase chain reaction have been used to identify LNM in patients with gastric cancer, the clinical significance of this finding remains unclear. Recently, minimally invasive treatments, such as endoscopic submucosal dissection and laparoscopic surgery, are widely performed to help improve postsurgical quality of life (QOL). However, it is important to maintain the balance between QOL and curability when making treatments decision for patients with gastric cancer. If minimally invasive surgery based on accurate intraoperative LNM diagnosis was established, it could be performed safely. Therefore, we reviewed the clinical significance of LNM detected by molecular techniques as an important target for treatment decision making with gastric cancer patients. PMID:25320510

  4. The clinical significance of brain microbleeds in patients with Alzheimer's disease: Preliminary study

    PubMed Central

    Heo, Jae-Hyeok; Im, Dong-Gyu; Lee, Seung-Hyeon; Ahn, Jin-Young

    2016-01-01

    Background: Microbleeds (MBs) are observed frequently in Alzheimer's disease (AD) and suggested to play a crucial role in the pathophysiology, but their clinical significance remains unclear. Materials and Methods: The study recruited 100 patients with AD who were diagnosed at the memory clinic in Seoul Medical Center in 2014. For each patient, baseline characteristics, neuropsychological tests, cerebrovascular risk factors, medial temporal lobe atrophy (MTLA), and severity of small vessel disease (SVD) according to the existence of MBs were evaluated. Results: The prevalence of MBs in patients with AD was 33%. The percentage of male gender, the severity of SVD and MTLA were significantly increased in MB(+) group. The MB(+) group showed more severe MTLA and SVD than MB(−) group. Conclusions: These results suggested that MBs might reflect the burden of amyloid and ischemic vascular pathology. PMID:27994360

  5. Clinically significant hemodynamic alterations after propacetamol injection in the emergency department: prevalence and risk factors.

    PubMed

    Bae, June-Il; Ahn, Shin; Lee, Yoon-Seon; Kim, Won Young; Lee, Jae Ho; Oh, Bum Jin; Lim, Kyung Soo

    2017-04-01

    Propacetamol, a water-soluble prodrug form of paracetamol, is hydrolyzed by esterase to generate paracetamol in the blood. Each gram of propacetamol is equal to 0.5 g of paracetamol. It has been reported to cause hypotension in critically ill patients with a fever. We aimed to investigate the hemodynamic effects of propacetamol for the control of fever in patients with diverse severities of illness who were managed in the emergency department (ED). We also aimed to identify clinical factors related to significant hemodynamic alterations in ED patients. This was a retrospective study of 1507 ED patients who received propacetamol. Significant hemodynamic alterations were defined as systolic blood pressure (SBP) <90 mmHg or diastolic blood pressure (DBP) <60 mmHg, or a drop in SBP >30 mmHg, which required treatments with a bolus of fluid or vasopressor administration. Postinfusion SBP and DBP were significantly lower than the preinfusion SBP and DBP. A clinically significant drop in BP occurred in 162 (10.7 %) patients, and interventions were necessary. Among the predictors assessed, congestive heart failure (OR 6.21, 95 % CI 2.67-14.45) and chills (OR 3.10, 95 % CI 2.04-4.70) were independent factors for a significant hemodynamic change. Administration of propacetamol can provoke a reduction in BP in ED patients. This reduction was clinically significant for 10 % of infusions. Clinicians should be aware of this potential deleterious effect, especially in patients with congestive heart failure or who experience chills prior to the administration of propacetamol.

  6. Significance of molecular identification and antifungal susceptibility of clinically significant yeasts and moulds in a global antifungal surveillance programme.

    PubMed

    Pfaller, Michael A; Woosley, Leah N; Messer, Shawn A; Jones, Ronald N; Castanheira, Mariana

    2012-10-01

    The increasing diversity of opportunistic fungi causing serious invasive fungal infections (IFI) has been documented. Accurate identification (ID) is important in guiding therapy, determining prognosis for IFIs and in epidemiological surveys. We assessed the utility of PCR-based methods for the ID of yeasts and moulds that either were uncommon, failed conventional ID, or represented unusual biochemical or phenotypic profiles of common species. Among 1,790 viable fungal clinical isolates received during the SENTRY Program in 2010, 322 strains from 40 study sites had ID confirmed by molecular methods. Isolates were previously identified in participant institutions. Yeasts that were not confirmed by morphology on CHROMagar, growth at 45 °C (Candida albicans/dubliniensis), or assimilation of trehalose (C. glabrata) as well as non-Candida yeasts and all moulds were amplified and sequenced using primers amplifying one or more of the following genes: ITS, 28S, β-tubulin (Aspergillus spp.), TEF (Fusarium spp.), IGS (Trichosporon spp.). The isolates selected for molecular ID included 149 isolates of Candida species, 77 of Aspergillus species, 73 non-Candida yeasts, and 23 other moulds (a total of 41 different species). Overall, the ID determined by the submitting site was confirmed for 189 isolates (58.7 %): Aspergillus spp. (64.1 % correct); Candida spp. (60.1 % correct); non-Candida yeasts (58.9 % correct); non-Aspergillus moulds (30.4 % correct). Species with high levels of concordance between conventional and molecular ID included A. fumigatus (95.0  %), C. lusitaniae (100 %), C. dubliniensis (92.3 %), C. kefyr (100 %), and C. neoformans (90.2 %). Only 50.0 % of isolates of C. albicans and 59.1 % of C. glabrata selected due to unusual phenotypic or biochemical features were found to be correctly identified by the submitting site. Molecular methods for the identification of fungal pathogens are an important adjunct to the conventional identification of

  7. MMSA-1 expression pattern in multiple myeloma and its clinical significance.

    PubMed

    Meng, Shan; Lu, Chenyang; Zhang, Wanggang; Shen, Wenjun; Wei, Yongchang; Su, Dan; Zhou, Fuling

    2016-11-01

    Multiple myeloma-associated antigen-1 (MMSA-1) is a novel multiple myeloma (MM)-associated antigen which has been recently identified. Herein, we have tried to examine its clinical significance by studying the relationship between its expression and selected clinicopathological features. We extracted mononuclear cells from the bone marrow of MM patients and healthy donors and compared the MMSA-1 expression by RT-PCR and Western blot analysis. In addition, we also analyzed MMSA-1 expression in patients that were grouped based on selected clinical parameters. Moreover, the impact of MMSA-1 on patients' survival was also explored. MMSA-1 mRNA and protein were significantly upregulated in MM patients in comparison with healthy donors. Moreover, among the newly diagnosed and relapsed/refractory patients, the MMSA-1 expression was higher in relapsed/refractory patients. In addition, MMSA-1 mRNA expression not only showed significantly higher correlation with clinical parameters such as age, Durie and Salmon stage, bone lesion condition, albumin, creatinine and lactate dehydrogenase but also has a close relationship with myeloma bone disease-related cytokines, genetic abnormalities and treatment response. Multivariate COX analysis predicted MMSA-1 and LDH levels to be independently associated with a poor progression-free survival and overall survival in myeloma patients. Our findings provide initial proof of concept that MMSA-1 is a potent gene that is specifically expressed in MM patients and could be a feasible biomarker and independent prognostic factor.

  8. Systemic oxygen therapy versus oral enalapril for treatment of diabetic macular ischemia: a randomized controlled trial.

    PubMed

    Sharifipour, Farideh; Razzaghi, Mohammadreza; Ramezani, Alireza; Azarmina, Mohsen; Yaseri, Mehdi; Soheilian, Roham; Soheilian, Masoud

    2016-04-01

    The purpose of this study was to evaluate the structural and functional effects of systemic oxygen therapy and enalapril in patients with diabetic macular ischemia (DMI). This randomized clinical trial consisted of 105 eyes with DMI divided into three groups. Group I received systemic oxygen by face mask at a flow rate of 10 L/min; Group II received 5 mg enalapril daily; and Group III received placebo tablets for 3 months. Best-corrected visual acuity (BCVA), central macular thickness (CMT) measured by optical coherence tomography (OCT), extent of foveal avascular zone (FAZ) on fluorescein angiograms, and electroretinograms (ERG) were obtained at baseline and after 3 and 6 months. Overall, 102 patients completed the study. Baseline characteristics were not significantly different among groups. Significant improvement in BCVA and decrease in CMT and FAZ occurred at months 3 and 6 in oxygen group compared to deterioration in enalapril and control groups (All P values <0.001). ERG parameters were significantly better in oxygen group compared to enalapril group at months 3 and 6 and better than those in control group at month 3. Normobaric oxygen therapy for 3 months in DMI decreased CMT and FAZ and improved BCVA and ERG parameters. Enalapril did not show any favorable effect.

  9. Overexpression and clinical significance of MYC-associated zinc finger protein in pancreatic carcinoma

    PubMed Central

    Zhu, Xiaonian; Luo, Wei; Liang, Wenjin; Tang, Fen; Bei, Chunhua; Ren, Yuan; Qin, Linyuan; Tan, Chao; Zhang, Ying; Tan, Shengkui

    2016-01-01

    This study aimed to investigate the expression and clinical significance of MYC-associated zinc finger protein (MAZ) in pancreatic carcinoma (PC), and the biological functions of MAZ in PC cells. MAZ expression was detected in 57 PC tissues and 41 paired adjacent nontumor tissues by immunohistochemistry. Compared to the expression in adjacent nontumor tissues, MAZ was significantly higher expressed in PC tissues (P<0.0001). In addition, MAZ expression had a significant correlation with certain clinical characteristics of PC patients, such as age, tumor diameter, tumor number, and the serum level of CA199 (P<0.05). The survival analysis showed that the survival time of PC patients with high expression of MAZ was significantly lower than patients with low expression of MAZ (P=0.0365). After MAZ was knocked down in PANC-1 cells by RNA interference, the cells’ ability to proliferate, invade, and migrate was decreased significantly (P<0.01). Moreover, MAZ expression was found to be associated with Ki-67, a cell proliferation marker, in PC tissues, further supporting the idea that MAZ promotes PC cell proliferation. Our study clarifies an oncogenic role of MAZ in pathogenesis of PC and provides MAZ as a biomarker in the treatment and prognosis of PC. PMID:28008270

  10. Oral and silent reading performance with macular degeneration.

    PubMed

    Lovie-Kitchin, J E; Bowers, A R; Woods, R L

    2000-09-01

    Previous studies have shown that reading rate for very large print (6 degrees, 1.86 logMAR character size) is a strong predictor of oral reading rate with low vision devices (LVDs). We investigated whether this would apply using large print sizes more readily available in clinical situations (e.g. 2 degrees, 1.4 logMAR), for subjects with macular degeneration. We assessed rauding rates--reading for understanding. A combination of near word visual acuity and large print reading rate (without LVDs) provided the best prediction of oral rauding rates (with LVDs). However, near word visual acuity alone was almost as good. Similarly, silent rauding rate was predicted best by near word visual acuity alone. We give near visual acuity limits as a clinical guide to expected oral and silent reading performance with LVDs for patients with macular degeneration.

  11. Gene Therapies for Neovascular Age-Related Macular Degeneration.

    PubMed

    Pechan, Peter; Wadsworth, Samuel; Scaria, Abraham

    2014-12-18

    Pathological neovascularization is a key component of the neovascular form (also known as the wet form) of age-related macular degeneration (AMD) and proliferative diabetic retinopathy. Several preclinical studies have shown that antiangiogenesis strategies are effective for treating neovascular AMD in animal models. Vascular endothelial growth factor (VEGF) is one of the main inducers of ocular neovascularization, and several clinical trials have shown the benefits of neutralizing VEGF in patients with neovascular AMD or diabetic macular edema. In this review, we summarize several preclinical and early-stage clinical trials with intraocular gene therapies, which have the potential to reduce or eliminate the repeated intravitreal injections that are currently required for the treatment of neovascular AMD.

  12. Vitamin E supplementation and macular degeneration: randomised controlled trial

    PubMed Central

    Taylor, Hugh R; Tikellis, Gabriella; Robman, Luba D; McCarty, Catherine A; McNeil, John J

    2002-01-01

    Objective To determine whether vitamin E supplementation influences the incidence or rate of progression of age related maculopathy (AMD). Design Prospective randomised placebo controlled clinical trial. Setting An urban study centre in a residential area supervised by university research staff. Participants 1193 healthy volunteers aged between 55 and 80 years; 73% completed the trial on full protocol. Interventions Vitamin E 500 IU or placebo daily for four years. Main outcome measures Primary outcome: development of early age related macular degeneration in retinal photographs. Other measures included alternative definitions of age related macular degeneration, progression, changes in component features, visual acuity, and visual function Results The incidence of early age related macular degeneration (early AMD 3) was 8.6% in those receiving vitamin E versus 8.1% in those on placebo (relative risk 1.05, 95% confidence interval 0.69 to 1.61). For late disease the incidence was 0.8% versus 0.6% (1.36, 0.67 to 2.77). Further analysis showed no consistent differences in secondary outcomes. Conclusion Daily supplement with vitamin E supplement does not prevent the development or progression of early or later stages of age related macular degeneration. What is already known on this topicAge related macular degeneration is the leading cause of loss of vision and blindness in elderly people; for people aged ⩾90 years, two out of every three will be affected and one in four will become blindCurrently, there are no methods of prevention or treatment in most cases, though a third of cases are due to cigarette smokingAntioxidant vitamins have been suggested as a possible preventionWhat this study addsDaily supplementation with 500 mg vitamin E for four years did not alter the incidence or progression of AMD PMID:12098721

  13. [Clinical diagnose and significance of congenital sensorineural hearing loss combined with BPES].

    PubMed

    Ao, Liying; Liu, Yongzhi

    2015-09-01

    To analyze congenital sensorineural hearing loss combined with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES). For the case of cochlear implantation to child with congenital sensorineural deafness combined BPES, accomplish routine examination and assessment, combining with literature to analyze the clinical diagnosis of this disease and its significance. Sensorineural hearing loss is a common congenital diseases with neonatal incidence of 1 per thousand - 3 per thousand, 50%-70% of deafness is associated with genetic factors, the incidence of congenital sensorineural hearing loss combined with eye disease is about 40%-60%, mainly reflected in ametropia and retinopathy. BPES's main clinical manifestations is blepharophimosis, ptosis, epicanthus inversus, and telecanthus. BPES is a rare autosomal dominant disease caused by FOXL 2 gene mutation, sometimes associated with retarded growth, delayed development, congenital heart disease, and microcephaly. Suffering from both sensorineural hearing loss and BPES is rare in reported literature. This case is diagnosed by clinical examination, without visual impairment. Facial nerve dysplasia has been found during the surgery. For congenital deafness patients with eye disease or other diseases, timely and correct diagnosis has important clinical significance, which can improve the diagnostic rate and make it coming true to early intervention, and then, effectively improve the quality of the patients. There are few literature reports, of patients with two kinds of genetic diseases. Our inference is that the cases are rare or the patients has visited different departments and ignored the other systems' signs. Therefore, in such doubtful cases, we should do the professional comprehensive examination in daily clinical work in order to avoid missed diagnosis or delayed treatment and intervention. By analyzing this case, the patient may also suffer from facial nerve dysplasia. Preoperatively viewing CT scan and

  14. Evolving approach and clinical significance of detecting DNA mismatch repair deficiency in colorectal carcinoma

    PubMed Central

    Shia, Jinru

    2016-01-01

    The last two decades have seen significant advancement in our understanding of colorectal tumors with DNA mismatch repair (MMR) deficiency. The ever-emerging revelations of new molecular and genetic alterations in various clinical conditions have necessitated constant refinement of disease terminology and classification. Thus, a case with the clinical condition of hereditary non-polyposis colorectal cancer as defined by the Amsterdam criteria may be one of Lynch syndrome characterized by a germline defect in one of the several MMR genes, one of the yet-to-be-defined “Lynch-like syndrome” if there is evidence of MMR deficiency in the tumor but no detectable germline MMR defect or tumor MLH1 promoter methylation, or “familial colorectal cancer type X” if there is no evidence of MMR deficiency. The detection of these conditions carries significant clinical implications. The detection tools and strategies are constantly evolving. The Bethesda guidelines symbolize a selective approach that uses clinical information and tumor histology as the basis to select high-risk individuals. Such a selective approach has subsequently been found to have limited sensitivity, and is thus gradually giving way to the alternative universal approach that tests all newly diagnosed colorectal cancers. Notably, the universal approach also has its own limitations; its cost-effectiveness in real practice, in particular, remains to be determined. Meanwhile, technological advances such as the next-generation sequencing are offering the promise of direct genetic testing for MMR deficiency at an affordable cost probably in the near future. This article reviews the up-to-date molecular definitions of the various conditions related to MMR deficiency, and discusses the tools and strategies that have been used in detecting these conditions. Special emphasis will be placed on the evolving nature and the clinical importance of the disease definitions and the detection strategies. PMID:25716099

  15. Mechanism of an unusual, but clinically significant, digoxin-bupropion drug interaction.

    PubMed

    He, Jiake; Yu, Yang; Prasad, Bhagwat; Chen, Xijing; Unadkat, Jashvant D

    2014-07-01

    An unusual, but clinically significant, digoxin (DIG)-bupropion (BUP) drug interaction (DDI), in which BUP increased DIG renal clearance by 80% is reported. To investigate the mechanism(s) of this unusual DDI, first the effect of BUP, its circulating metabolites or their combination on [(3) H]-DIG transport by cells expressing human P-gp or human OATP4C1 was determined. Second, the study asked whether this DDI could be replicated in the rat so that it could be used to conduct mechanistic studies. Then, the effect of BUP and its rat metabolites on [(3) H]-DIG transport were tested by cells expressing rat Oatp4c1. Bupropion and its metabolites had no effect on human P-gp mediated transepithelial transport of [(3) H]-DIG. Bupropion and hydroxybupropion (HBUP) significantly stimulated H-OATP4C1 mediated transport of [(3) H]-DIG. In addition, BUP cocktail (BUP plus its metabolites) significantly increased the H-OATP4C1 mediated transport of [(3) H]-DIG, and partially reversed the inhibition by 100 µm DIG. However, erythro-hydrobupropion (EBUP) and threo-hydrobupropion (TBUP) did not affect the [(3) H]-DIG uptake by H-OATP4C1 cells. Bupropion administration significantly increased digoxin renal clearance in rats. Surprisingly, bupropion significantly inhibited r-Oatp4c1 mediated transport of [(3) H]-DIG at clinically relevant unbound plasma concentrations of BUP or those observed in the rat study, while HBUP or TBUP did not. These data support our hypothesis that at clinically relevant plasma concentrations, bupropion and its metabolites activate H-OATP4C1 mediated DIG tubular secretion, and could possibly explain the increase in digoxin renal clearance produced by bupropion. While bupropion increased digoxin renal clearance in the rat, it appeared to do so by inhibiting r-Oatp4c1-mediated digoxin renal reabsorption.

  16. Clinical Significance of Commensal Gram-Positive Rods Routinely Isolated from Patient Samples.

    PubMed

    Leal, Sixto M; Jones, Melissa; Gilligan, Peter H

    2016-12-01

    Commensal bacteria from the skin and mucosal surfaces are routinely isolated from patient samples and considered contaminants. The majority of these isolates are catalase-positive Gram-positive rods from multiple genera routinely classified as diphtheroids. These organisms can be seen upon Gram staining of clinical specimens or can be isolated as the predominant or pure species in culture, raising a priori suspicion of a possible involvement in infection. With the development and adoption of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), suspicious isolates are now routinely identified to the species level. In this study, we performed a retrospective data review (2012 to 2015) and utilized site-specific laboratory criteria and chart reviews to identify species within the diphtheroid classification representative of true infection versus contamination. Our data set included 762 isolates from 13 genera constituting 41 bacterial species. Only 18% represented true infection, and 82% were deemed contaminants. Clinically significant isolates were identified in anaerobic wounds (18%), aerobic wounds (30%), blood (5.5%), urine (22%), cerebrospinal fluid (24%), ophthalmologic cultures (8%), and sterile sites (20%). Organisms deemed clinically significant included multiple Actinomyces species in wounds, Propionibacterium species in joints and cerebrospinal fluid associated with central nervous system hardware, Corynebacterium kroppenstedtii (100%) in breast, and Corynebacterium striatum in multiple sites. Novel findings include clinically significant urinary tract infections by Actinomyces neuii (21%) and Corynebacterium aurimucosum (21%). Taken together, these findings indicate that species-level identification of diphtheroids isolated with a priori suspicion of infection is essential to accurately determine whether an isolate belongs to a species associated with specific types of infection.

  17. Role of Barium Swallow in Diagnosing Clinically Significant Anastomotic Leak following Esophagectomy

    PubMed Central

    Roh, Simon; Iannettoni, Mark D.; Keech, John C.; Bashir, Mohammad; Gruber, Peter J.; Parekh, Kalpaj R.

    2016-01-01

    Background Barium swallow is performed following esophagectomy to evaluate the anastomosis for detection of leaks and to assess the emptying of the gastric conduit. The aim of this study was to evaluate the reliability of the barium swallow study in diagnosing anastomotic leaks following esophagectomy. Methods Patients who underwent esophagectomy from January 2000 to December 2013 at our institution were investigated. Barium swallow was routinely done between days 5–7 to detect a leak. These results were compared to clinically determined leaks (defined by neck wound infection requiring jejunal feeds and or parenteral nutrition) during the postoperative period. The sensitivity and specificity of barium swallow in diagnosing clinically significant anastomotic leaks was determined. Results A total of 395 esophagectomies were performed (mean age, 62.2 years). The indications for the esophagectomy were as follows: malignancy (n=320), high-grade dysplasia (n=14), perforation (n=27), benign stricture (n=7), achalasia (n=16), and other (n=11). A variety of techniques were used including transhiatal (n=351), McKeown (n=35), and Ivor Lewis (n=9) esophagectomies. Operative mortality was 2.8% (n=11). Three hundred and sixty-eight patients (93%) underwent barium swallow study after esophagectomy. Clinically significant anastomotic leak was identified in 36 patients (9.8%). Barium swallow was able to detect only 13/36 clinically significant leaks. The sensitivity of the swallow in diagnosing a leak was 36% and specificity was 97%. The positive and negative predictive values of barium swallow study in detecting leaks were 59% and 93%, respectively. Conclusion Barium swallow is an insensitive but specific test for detecting leaks at the cervical anastomotic site after esophagectomy. PMID:27066433

  18. Unusual Presentation of Type 1 Idiopathic Macular Telangiectasia

    PubMed Central

    Denis, Philippe

    2017-01-01

    Purpose. To report unusual presentation of type 1A idiopathic macular telangiectasia (IMT). Methods. Two middle-aged women with bilateral IMT were examined. Results. Both patients presented with a gradual vision loss in both eyes. Fundus examination was unremarkable in one case and showed small macular telangiectasia in both eyes in the other case. Fluorescein angiography (FA) revealed early bilateral macular punctuated hyperfluorescence corresponding to the dilated capillaries in both cases. FA and fundus examination confirmed also the absence of vascular abnormalities in the middle or anterior fundus periphery in one case. Spectral-domain optical coherence tomography (SD-OCT) showed cystoid macular edema in both cases. No signs of retinal vein occlusions were detected in both cases and other differential diagnoses were excluded. Based on these findings, the patients were diagnosed with bilateral type 1A IMT according to Gass and Blodi classification and were treated with intravitreal antivascular endothelial growth factor (anti-VEGF) injections and focal laser photocoagulation. Twelve months later, SD-OCT revealed partial regression of the exudative signs and significant VA improvement. Conclusion. We described two patients with an unusual presentation of type 1A IMT with bilateral presentation, affecting two middle-aged women, with occult and without peripheral involvement in one case. The description of more cases of bilateral type 1 IMT should be helpful to more precisely define the pathophysiologic mechanism that could be different from a localized Coats' disease of the macula area. PMID:28203470

  19. Occurrence and clinical significance of Aelurostrongylus abstrusus and other endoparasites in Danish cats.

    PubMed

    Hansen, Alice P; Skarbye, Line K; Vinther, Lene M; Willesen, Jakob L; Pipper, Christian B; Olsen, Caroline S; Mejer, Helena

    2017-01-30

    Feline endoparasites are highly prevalent worldwide and may cause a variety of clinical signs in infected cats. Prevalence rates are dynamic and there is limited knowledge of the current prevalence in Denmark and the clinical manifestation and significance of especially the lungworm Aelurostrongylus abstrusus. This study investigated the total and local prevalence of Aelurostrongylus abstrusus and other endoparasites in Danish cats. The clinical significance of feline aelurostrongylosis was also examined through identification of frequency and severity of selected clinical signs. Faecal samples (n=327) and clinical data (n=312) were collected from August to October 2015, primarily from outdoor cats located at shelters distributed across Denmark. A modified Baermann method and a concentration McMaster technique was used to diagnose A. abstrusus first stage larvae and eggs/oocysts of other endoparasites. The total A. abstrusus prevalence was 8.3% [95% CI: 5.6-11.9] but local prevalence rates varied from 0% [95% CI: 0.0-8.8] to 31.4% [95% CI: 16.9-49.3]. A rural habitat appeared to increase the risk of A. abstrusus and this accounted for most of the local variation. Furthermore, the risk of infection was lower in kittens younger than 11 weeks compared to older cats (p=0.002). The cats were also infected with Toxocara cati (44.4% [95% CI: 38.3-50.7]), taeniid species (8.9% [95% CI: 5.7-13.0]), Capillaria aerophila (3.1% [95% CI: 1.3-6.0]), Aonchotheca putorii (3.9% [95% CI: 1.9-7.0]), Cystoisospora felis (3.1% [95% CI: 1.3-6.0]) and Cystoisospora rivolta (2.3% [95% CI: 0.9-5.0]), but there was no difference in local distribution. Co-infection was common, as 66.7% of A. abstrusus infected cats were also infected with one or more other parasites, the most common being T. cati. However, none of these parasites were significantly associated with A. abstrusus. The vast majority of the A. abstrusus infected cats displayed mild to moderate clinical signs. The main symptoms

  20. Complement pathway biomarkers and age-related macular degeneration

    PubMed Central

    Gemenetzi, M; Lotery, A J

    2016-01-01

    In the age-related macular degeneration (AMD) ‘inflammation model', local inflammation plus complement activation contributes to the pathogenesis and progression of the disease. Multiple genetic associations have now been established correlating the risk of development or progression of AMD. Stratifying patients by their AMD genetic profile may facilitate future AMD therapeutic trials resulting in meaningful clinical trial end points with smaller sample sizes and study duration. PMID:26493033

  1. Early detection of age related macular degeneration: current status.

    PubMed

    Schwartz, Roy; Loewenstein, Anat

    2015-01-01

    Early diagnosis and treatment of choroidal neovascularization (CNV), a main cause of severe vision loss in age related macular degeneration (AMD), is crucial in order to preserve vision and the quality of life of patients. This review summarizes current literature on the subject of early detection of CNV, both in the clinic setting and mainly in the patient's home. New technologies are evolving to allow for earlier detection and thus vision preservation in AMD patients.

  2. [Therapeutic approach in persistent diabetic macular edema].

    PubMed

    Brănişteanu, Daniel; Moraru, Andreea

    2014-01-01

    Terminology of persistent diabetic macular edema has been initially reserved to cases unresponsive to conventional laser photocoagulation according to ETDRS criteria. While knowledge about pathophysiology of macular edema evolved and new drugs became available, the terminology of persistent diabetic macular edema expanded to include resistance to most current therapies. The purpose of this paper is to review medical and surgical options in the treatment of such difficult cases according to literature data and personal experience.

  3. Morphision: A method for subjective evaluation of metamorphopsia in patients with unilateral macular pathology (i.e., full thickness macular hole and epiretinal membrane)

    PubMed Central

    Ugarte, Marta; Shunmugam, Manoharan; Laidlaw, D Alistair H; Williamson, Tom H

    2013-01-01

    Background: Lack of clinical tests to quantify spatial components of distortion in patients with full thickness macular holes (FTMH) and epiretinal membranes (ERM). Aim: To develop a test for subjective evaluation of visual distortion in the central visual field around fixation in patients with unilateral FTMH or ERM. Settings and Design: Prospective case-control study carried out at tertiary referral center. Materials and Methods: Twenty-five patients with unilateral macular disease (13 macular epiretinal membranes, 12 full-thickness macular holes), and nine controls (without ocular pathology) underwent ophthalmological examination with logMAR ETDRS visual acuity, near vision and contrast sensitivity assessed. Macular optical coherence tomography and metamorphopsia assessment using Morphision test was also carried out. This test consists of a set of modified Amsler charts for detection, identification, and subjective quantification of visual distortion in the central visual field around fixation. Morphision test content and construct validity, and reliability (test-retest method) were evaluated. Sixteen patients completed an unstructured survey on test performance and preference. Results: Every patient with unilateral FTMH or ERM identified a particular chart using Morphision test (content validity). None of the normal subjects without symptoms of metamorphopsia identified any distortion (construct validity). Test-retest showed a 100% consistency for frequency and 67% for amplitude. The mean amplitude difference between measurements was 0.02 degrees (SD = 0.038). The coefficient of repeatability was 0.075. There was a correlation between Morphision amplitude score and visual acuity and contrast sensitivity, individually. Conclusions: Morphision test allowed detection and subjective quantification of metamorphopsia in the clinical setting in our patients with unilateral macular epiretinal membranes and full thickness macular holes. PMID:24008785

  4. Significant alterations in reported clinical practice associated with increased oversight of organ transplant center performance.

    PubMed

    Schold, Jesse D; Arrington, Charlotte J; Levine, Greg

    2010-09-01

    In the past several years, emphasis on quality metrics in the field of organ transplantation has increased significantly, largely because of the new conditions of participation issued by the Centers for Medicare and Medicaid Services. These regulations directly associate patients' outcomes and measured performance of centers with the distribution of public funding to institutions. Moreover, insurers and marketing ventures have used publicly available outcomes data from transplant centers for business decision making and advertisement purposes. We gave a 10-question survey to attendees of the Transplant Management Forum at the 2009 meeting of the United Network for Organ Sharing to ascertain how centers have responded to the increased oversight of performance. Of 63 responses, 55% indicated a low or near low performance rating at their center in the past 3 years. Respondents from low-performing centers were significantly more likely to indicate increased selection criteria for candidates (81% vs 38%, P = .001) and donors (77% vs 31%, P < .001) as well as alterations in clinical protocols (84% vs 52%, P = .007). Among respondents indicating lost insurance contracts (31%), these differences were also highly significant. Based on respondents' perceptions, outcomes of performance evaluations are associated with significant changes in clinical practice at transplant centers. The transplant community and policy makers should practice vigilance that performance evaluations and regulatory oversight do not inadvertently lead to diminished access to care among viable candidates or decreased transplant volume.

  5. Clinical and molecular significance of microvascular inflammation in transplant kidney biopsies.

    PubMed

    Gupta, Anjali; Broin, Pilib Ó; Bao, Yi; Pullman, James; Kamal, Layla; Ajaimy, Maria; Lubetzky, Michelle; Colovai, Adriana; Schwartz, Daniel; de Boccardo, Graciela; Golden, Aaron; Akalin, Enver

    2016-01-01

    The diagnostic criteria for antibody-mediated rejection (AMR) are continuously evolving. Here we investigated the clinical and molecular significance of different Banff microvascular inflammation (MVI) scores in transplant kidney biopsies. A total of 356 patients with clinically indicated kidney transplant biopsies were classified into three groups based on MVI scores of 0, 1, 2, or more for Groups 1-3, respectively. Gene expression profiles were assessed using arrays on a representative subset of 93 patients. The incidence of donor-specific anti-HLA antibodies was increased from 25% in Group 1 to 36% in Group 2 and to 54% in Group 3. Acute and chronic AMR were significantly more frequent in Group 3 (15% and 35%) compared with the Group 2 (3% and 15%) and Group 1 (0% and 5%), respectively. Gene expression profiles showed increased interferon-γ and rejection-induced, cytotoxic and regulatory T-cell, natural killer cell-associated and donor-specific antibody (DSA)-selective transcripts in Group 3 compared with Groups 1 and 2. There was no significant difference in gene expression profiles between the Groups 1 and 2. Increased intragraft expression of DSA-selective transcripts was found in the biopsies of C4d- Group 3 patients. Thus, an MVI score of 2 or more was significantly associated with a histological diagnosis of acute and chronic antibody-mediated rejection. Hence, increased intragraft DSA-selective gene transcripts may be used as molecular markers for AMR, especially in C4d- biopsies.

  6. Contextual cognitive-behavioral therapy for severely disabled chronic pain sufferers: effectiveness and clinically significant change.

    PubMed

    McCracken, Lance M; MacKichan, Fiona; Eccleston, Christopher

    2007-04-01

    Interdisciplinary pain management programs have an established record of significantly improving the functioning of persons disabled with chronic pain. There is a group of pain sufferers, however, who have difficulty accessing these programs and for whom the effectiveness of these treatments in unknown, these are patients whose mobility and self-care deficits leave them unable to meet the practical demands of many treatment environments. The purpose of this study was to examine the results of a treatment program designed to meet the needs of these highly disabled individuals (n=53) in comparison to results obtained from a standard less-disabled group attending treatment at the same facility (n=234). Results from the highly disabled patients showed statistically significant change after treatment in eight of nine outcome variables, including improvements in pain-related distress, disability, depression, pain-related anxiety, daytime rest, and performance during an activity tolerance test. Effect size calculations showed a number of large treatment effects, for psychosocial disability, depression, and acceptance of pain. Analysis of reliable change and clinical significance demonstrated that results were not merely statistically significant but clinically meaningful. Results appeared stable at three months following treatment. This research plays an important part in establishing an evidence base to inform service development, ensuring that chronic pain services do not exclude people on the basis of the severity of their disability.

  7. Clinical significance of a new autoantibody against a human eye muscle soluble antigen, detected by immunofluorescence.

    PubMed Central

    Mengistu, M; Laryea, E; Miller, A; Wall, J R

    1986-01-01

    The clinical significance of a circulating autoantibody against a recently identified soluble human eye muscle-derived antigen was studied in patients with Graves' ophthalmopathy and autoimmune thyroid disorders. Tests were positive in 73% of patients with Graves' ophthalmopathy, including six of seven with no associated thyroid disease (euthyroid Graves' disease). Tests were also positive in 27% of patients with hyperthyroidism but no clinically apparent eye disease, in 13% of patients with Hashimoto's thyroiditis without eye disease, in two of 12 patients with subacute thyroiditis, in one of 20 patients with nonimmunological thyroid disorders but in none of 39 normal subjects. There were significant positive correlations between serum levels of the antibody (expressed as a titre) and the severity of the eye muscle component quantified as an index as well as the duration of the eye disease. Antibodies were detected in three of five patients with only lid lag and state who subsequently developed active ophthalmopathy, in six of nine patients who developed eye disease after treatment of their hyperthyroidism and in one of eight first degree relatives of patients with Graves' ophthalmopathy. In addition three of the 12 patients with autoimmune thyroid disease without apparent eye involvement, but positive antibody tests, have developed ophthalmopathy since the time of testing. These findings suggest that tests for antibodies against a soluble human eye muscle antigen may be useful clinically as a diagnostic test and to predict the onset of eye disease in predisposed patients and subjects. PMID:3539423

  8. Anti-vascular endothelial growth factor therapy for diabetic macular edema

    PubMed Central

    Hopkins, J. Jill; Sorof, Jonathan; Ehrlich, Jason S.

    2013-01-01

    Diabetes mellitus is a serious health problem that affects over 350 million individuals worldwide. Diabetic retinopathy (DR), which is the most common microvascular complication of diabetes, is the leading cause of new cases of blindness in working-aged adults. Diabetic macular edema (DME) is an advanced, vision-limiting complication of DR that affects nearly 30% of patients who have had diabetes for at least 20 years and is responsible for much of the vision loss due to DR. The historic standard of care for DME has been macular laser photocoagulation, which has been shown to stabilize vision and reduce the rate of further vision loss by 50%; however, macular laser leads to significant vision recovery in only 15% of treated patients. Mechanisms contributing to the microvascular damage in DR and DME include the direct toxic effects of hyperglycemia, sustained alterations in cell signaling pathways, and chronic microvascular inflammation with leukocyte-mediated injury. Chronic retinal microvascular damage results in elevation of intraocular levels of vascular endothelial growth factor A (VEGF), a potent, diffusible, endothelial-specific mitogen that mediates many important physiologic processes, including but not limited to the development and permeability of the vasculature. The identification of VEGF as an important pathophysiologic mediator of DME suggested that anti-VEGF therapy delivered to the eye might lead to improved visual outcomes in this disease. To date, four different inhibitors of VEGF, each administered by intraocular injection, have been tested in prospective, randomized phase II or phase III clinical trials in patients with DME. The results from these trials demonstrate that treatment with anti-VEGF agents results in substantially improved visual and anatomic outcomes compared with laser photocoagulation, and avoid the ocular side effects associated with laser treatment. Thus, anti-VEGF therapy has become the preferred treatment option for the

  9. [Pathogenesis of age-related macular degeneration].

    PubMed

    Kaarniranta, Kai; Seitsonen, Sanna; Paimela, Tuomas; Meri, Seppo; Immonen, Ilkka

    2009-01-01

    Age-related macular degeneration is a multiform disease of the macula, the region responsible for detailed central vision. In recent years, plenty of new knowledge of the pathogenesis of this disease has been obtained, and the treatment of exudative macular degeneration has greatly progressed. The number of patients with age-related macular degeneration will multiply in the following decades, because knowledge of mechanisms of development of macular degeneration that could be subject to therapeutic measures is insufficient. Central underlying factors are genetic inheritance, exposure of the retina to chronic oxidative stress and accumulation of inflammation-inducing harmful proteins into or outside of retinal cells.

  10. Comparison of Central Macular Thickness Measured by Three OCT Models and Study of Interoperator Variability

    PubMed Central

    Bentaleb-Machkour, Zaïnab; Jouffroy, Eléonore; Rabilloud, Muriel; Grange, Jean-Daniel; Kodjikian, Laurent

    2012-01-01

    Purpose. To compare central macular thickness (CMT) measurement on healthy patient using 3 different OCT devices by two operators. Methods. Prospective, monocentricstudy. Right eye's central macular thickness (CMT) of 30 healthy patients has been measured three times using a time-domain (TD) OCT (Stratus OCT, Carl Zeiss Meditec, Dublin, Ca) and two spectral domain (SD) OCTs (Cirrus HD-OCT, Carl ZeissMeditec, Dublin, Ca) and 3D-OCT 1000 (Topcon, Tokyo, Japan) by two operators. Six measurements were taken randomly for each patient the same day. Results. No significant difference between measurements obtained by the two operators has been observed, whatever the studied OCT. P value was 0.164, 0.193, and 0.147 for Stratus OCT, Cirrus HD-OCT and 3D-OCT, respectively. Mean CMT significantly differed from instrument to instrument (P < 0.001) and was, respectively, 197 μm, 254 μm, and 236 μm using Stratus OCT, Cirrus HD-OCT, and 3D-OCT 1000. Using Cirrus OCT and 3D-OCT 1000, CMT was, respectively, 57 μm and 39 μm thicker than using Stratus OCT (P < 0.05). Conclusions. Whatever the OCT device, on healthy patients CMT was not operator dependent. CMT measurements obtained by SD-OCTs are greater than those obtained by TD-OCT. These data imply that the different OCT devices cannot be used interchangeably in clinical monitoring. PMID:22973177

  11. The clinical significance of the Ezrin gene and circulating tumor cells in osteosarcoma

    PubMed Central

    Zhong, Guang-Xian; Feng, Shao-Dan; Shen, Rongkai; Wu, Zhao-Yang; Chen, Fei; Zhu, Xia

    2017-01-01

    Purpose The aim of this study was to investigate the clinical significance of circulating tumor cells (CTCs) in the peripheral blood of an osteosarcoma and the Ezrin gene expressed in CTCs. Patients and methods CTC enrichment was done with CanPatrol™ CTC enrichment technique in 41 patients with osteosarcoma. The characterization of CTCs was performed using a multiple messenger RNA in situ analysis (MRIA). The expression of the Ezrin gene in CTCs was detected by RNA probe technology. The correlations of CTC counts, cell type and the expression level of the Ezrin gene with clinical stage and metastasis of osteosarcoma were analyzed using SPSS 16.0 software. Results The CTC counts correlated significantly with Enneking stage (P<0.001). The ratio of mesenchymal CTCs correlated with the distant metastases (P<0.001). Ezrin gene expression in CTCs correlated significantly with distant metastases (χ2=152.51, P=0.000). Conclusion The ratio of mesenchymal CTCs in the peripheral blood of osteosarcoma correlates with distant metastases. High expression of Ezrin gene in CTCs correlates with distant metastases. PMID:28223819

  12. Clinical significance of radiation-induced CD133 expression in residual rectal cancer cells after chemoradiotherapy.

    PubMed

    Kawamoto, Aya; Tanaka, Koji; Saigusa, Susumu; Toiyama, Yuji; Morimoto, Yuhki; Fujikawa, Hiroyuki; Iwata, Takashi; Matsushita, Kohei; Yokoe, Takeshi; Yasuda, Hiromi; Inoue, Yasuhiro; Miki, Chikao; Kusunoki, Masato

    2012-03-01

    CD133 and CD44 have been considered as markers for colorectal cancer stem cells (CSCs). The association of CD133 and CD44 expression with radiation has not been fully examined in rectal cancer. Both CD133 (PROM) and CD44 mRNA levels were measured in post-chemoradiotherapy (CRT) specimens of 52 rectal cancer patients using real-time RT-PCR and compared to clinicopathological variables and clinical outcome. Their protein levels were examined in the radiation-treated HT29 human colon cancer cell line. Post-CRT CD133 in residual cancer cells was significantly higher than matched pre-CRT CD133 in biopsy specimens (n=30). By contrast, CD44 was significantly lower in post-CRT specimens (P<0.01). CD133 was associated with distant recurrence after CRT followed by surgery (P<0.05). Patients with elevated CD133 in residual cancer cells showed poor disease-free survival (P<0.05). No significant association between post-CRT CD44 and clinical outcome was found. The in vitro study showed that CD133 protein was increased in a radiation dose-dependent manner, despite of the decreased number of clonogenic radiation-surviving cells. CD44 protein was decreased after irradiation. CD133, but not CD44, was increased in radiation-resistant surviving colon cancer cells. Post-CRT CD133 in residual cancer cells may predict metachronous distant recurrence and poor survival of rectal cancer patients after CRT.

  13. Managing clinically significant findings in research: the UK10K example.

    PubMed

    Kaye, Jane; Hurles, Matthew; Griffin, Heather; Grewal, Jasote; Bobrow, Martin; Timpson, Nic; Smee, Carol; Bolton, Patrick; Durbin, Richard; Dyke, Stephanie; Fitzpatrick, David; Kennedy, Karen; Kent, Alastair; Muddyman, Dawn; Muntoni, Francesco; Raymond, Lucy F; Semple, Robert; Spector, Tim

    2014-09-01

    Recent advances in sequencing technology allow data on the human genome to be generated more quickly and in greater detail than ever before. Such detail includes findings that may be of significance to the health of the research participant involved. Although research studies generally do not feed back information on clinically significant findings (CSFs) to participants, this stance is increasingly being questioned. There may be difficulties and risks in feeding clinically significant information back to research participants, however, the UK10K consortium sought to address these by creating a detailed management pathway. This was not intended to create any obligation upon the researchers to feed back any CSFs they discovered. Instead, it provides a mechanism to ensure that any such findings can be passed on to the participant where appropriate. This paper describes this mechanism and the specific criteria, which must be fulfilled in order for a finding and participant to qualify for feedback. This mechanism could be used by future research consortia, and may also assist in the development of sound principles for dealing with CSFs.

  14. Managing clinically significant findings in research: the UK10K example

    PubMed Central

    Kaye, Jane; Hurles, Matthew; Griffin, Heather; Grewal, Jasote; Bobrow, Martin; Timpson, Nic; Smee, Carol; Bolton, Patrick; Durbin, Richard; Dyke, Stephanie; Fitzpatrick, David; Kennedy, Karen; Kent, Alastair; Muddyman, Dawn; Muntoni, Francesco; Raymond, Lucy F; Semple, Robert; Spector, Tim

    2014-01-01

    Recent advances in sequencing technology allow data on the human genome to be generated more quickly and in greater detail than ever before. Such detail includes findings that may be of significance to the health of the research participant involved. Although research studies generally do not feed back information on clinically significant findings (CSFs) to participants, this stance is increasingly being questioned. There may be difficulties and risks in feeding clinically significant information back to research participants, however, the UK10K consortium sought to address these by creating a detailed management pathway. This was not intended to create any obligation upon the researchers to feed back any CSFs they discovered. Instead, it provides a mechanism to ensure that any such findings can be passed on to the participant where appropriate. This paper describes this mechanism and the specific criteria, which must be fulfilled in order for a finding and participant to qualify for feedback. This mechanism could be used by future research consortia, and may also assist in the development of sound principles for dealing with CSFs. PMID:24424120

  15. Expression of HIF-2α and VEGF in Cervical Squamous Cell Carcinoma and Its Clinical Significance

    PubMed Central

    Zhang, Lixia; Chen, Qiang; Hu, Jing; Chen, Yue; Liu, Chenglong; Xu, Changshui

    2016-01-01

    CSCC is a systemic disease involving polygenic alteration and multiple steps, and HIF and VEGF are closely associated with tumorigenesis. Specimens surgically resected from 64 cases of CSCC and 22 cases of normal cervical tissue were selected randomly to detect the expression of HIF-2α and VEGF in CSCC for exploring their clinical significance; information regarding the age, lymph node metastasis, and FIGO staging were collected as well; expression of HIF-2α and VEGF was detected by qPCR and immunohistochemistry. We found that the expression of HIF-2α and VEGF mRNA in CSCC was significantly higher than that of normal cervical tissues and showed a positive correlation between them. The positive rates of HIF-2α and VEGF protein expression in CSCC and normal cervical tissues were 93.8% and 18.2%, respectively, with correlation between them. The expression of both HIF-2α and VEGF mRNA did not relate closely to age but the FIGO staging and lymph node metastasis. Compared with the counterpart control group, CSCC tissues with high FIGO staging and lymph node metastasis had a higher level of HIF-2α and VEGF mRNA expression. So, HIF-2α and VEGF were overexpressed in CSCC, which has a great clinical significance for its diagnosis. PMID:27413748

  16. Clinically Significant Behavior Problems among Young Children 2 Years after the Great East Japan Earthquake

    PubMed Central

    Fujiwara, Takeo; Yagi, Junko; Homma, Hiroaki; Mashiko, Hirobumi; Nagao, Keizo; Okuyama, Makiko

    2014-01-01

    Background On March 11, 2011, a massive undersea earthquake and tsunami struck East Japan. Few studies have investigated the impact of exposure to a natural disaster on preschool children. We investigated the association of trauma experiences during the Great East Japan Earthquake on clinically significant behavior problems among preschool children 2 years after the earthquake. Method Participants were children who were exposed to the 2011 disaster at preschool age (affected area, n = 178; unaffected area, n = 82). Data were collected from September 2012 to June 2013 (around 2 years after the earthquake), thus participants were aged 5 to 8 years when assessed. Severe trauma exposures related to the earthquake (e.g., loss of family members) were assessed by interview, and trauma events in the physical environment related to the earthquake (e.g. housing damage), and other trauma exposure before the earthquake, were assessed by questionnaire. Behavior problems were assessed by caregivers using the Child Behavior Checklist (CBCL), which encompasses internalizing, externalizing, and total problems. Children who exceeded clinical cut-off of the CBCL were defined as having clinically significant behavior problems. Results Rates of internalizing, externalizing, and total problems in the affected area were 27.7%, 21.2%, and 25.9%, respectively. The rate ratio suggests that children who lost distant relatives or friends were 2.36 times more likely to have internalizing behavior problems (47.6% vs. 20.2%, 95% CI: 1.10–5.07). Other trauma experiences before the earthquake also showed significant positive association with internalizing, externalizing, and total behavior problems, which were not observed in the unaffected area. Conclusions One in four children still had behavior problems even 2 years after the Great East Japan Earthquake. Children who had other trauma experiences before the earthquake were more likely to have behavior problems. These data will be

  17. Prevalence and Clinical Significance of Night Eating Syndrome in University Students

    PubMed Central

    Runfola, Cristin D.; Allison, Kelly C.; Hardy, Kristina K.; Lock, James; Peebles, Rebecka

    2014-01-01

    Purpose Most studies of night eating syndrome (NES) fail to control for binge eating, despite moderate overlap between the two conditions. Establishing the independent clinical significance of NES is imperative for it to be considered worthy of clinical attention. We compared students with and without NES on eating disorder symptomatology, quality of life, and mental health, while exploring the role of binge eating in associations. Methods Students (N=1636) ages 18 to 26 (M=20.9) recruited from ten U.S. universities completed an online survey including the Night Eating Questionnaire (NEQ), Eating Disorder Examination-Questionnaire (EDE-Q), Project Eating Among Teens, and the Health-Related Quality of Life-4. NES was diagnosed according to endorsement of proposed diagnostic criteria on the NEQ. Groups (NES vs. non-NES) were compared on all dependent variables and stratified by binge eating status in secondary analyses. Results The prevalence of NES in our sample was 4.2%; it was 2.9% after excluding those with binge eating. Body mass index did not differ between groups, but students with NES were significantly more likely to have histories of underweight and anorexia nervosa. In students with NES, EDE-Q scores were significantly higher; purging, laxative use, and compulsive exercise were more frequent; quality of life was reduced; and histories of depression, attention-deficit/hyperactivity disorder, and self-injury were more common. Binge eating did not account for all of these differences; the presence of it and NES was associated with additive risk for psychopathology on some items. Conclusions NES may be a distinct clinical entity from other DSM-5 eating disorders. PMID:24485551

  18. The Clinical Significance of CD169-Positive Lymph Node Macrophage in Patients with Breast Cancer

    PubMed Central

    Yamamoto-Ibusuki, Mutsuko; Yamamoto, Yutaka; Iwase, Hirotaka; Takeya, Motohiro; Komohara, Yoshihiro

    2016-01-01

    The immune status of patients can impact on the clinical course of cancer. Lymph node (LN) macrophages play critical roles in anti-cancer immunity via the activation of cytotoxic T-lymphocytes (CTLs). In this study, the prognostic significance of CD169+ LN macrophages was examined in patients with breast cancer. For this purpose the number of CD169+ cells and their ratio relative to total macrophages (CD68+) in regional LNs (RLNs), as well as the number of CD8+ CTLs in tumor tissues, were investigated using immunohistochemistry of paraffin-embedded tissue samples from 146 patients with breast cancer. The association of these data with clinicopathological factors was then analyzed. The number of cells positive for the pan-macrophage marker CD68 remained relatively uniform, while the number of CD169+ cells varied across all cases. Moreover, a high density of CD169+ cells correlated with early clinical stage and no LN metastasis, while a higher CD169+ to CD68+ ratio was significantly associated with small tumor size and a low Ki-67+ rate. There was also a significant correlation between the number of CD8+ CTLs and that of CD169+ macrophages in high grade breast cancer cases with a Ki-67 index greater than 40%. However, neither the density nor the ratio of CD169+ cells, nor the density of CD8+ CTLs, were associated with relapse-free survival, distant relapse-free survival, or breast cancer-specific survival. These findings suggest that CD169+ macrophages in RLNs might be a useful marker for assessing clinical stage, including LN states, in patients with breast cancer. PMID:27861544

  19. Diagnostic value and clinical significance of stress hormones in patients with tinnitus.

    PubMed

    Kim, Dong-Kee; Chung, Dae Young; Bae, Seung Chun; Park, Kyoung-Ho; Yeo, Sang Won; Park, Shi-Nae

    2014-11-01

    Tinnitus has been found to be modulated by stress and is also closely related to the emotional state and the limbic system. In the present study, we evaluated the diagnostic and clinical values of several stress hormones in a large number of tinnitus patients. This study included 344 patients with sensorineural tinnitus and 87 normal controls. A questionnaire about tinnitus was administered to the participants, and blood levels of norepinephrine (NE), epinephrine (Epi), a metabolite of serotonin (5-hydroxyindoleacetic acid, 5-HIAA) and cortisol were compared between groups. In results, the mean values of Beck's depression inventory (BDI), Brief Encounter Psychosocial Instrument (BEPSI), NE, and 5-HIAA levels were higher in the tinnitus group, although there was no statistical significance. But, the proportion of participants with elevated 5-HIAA was significantly higher in the tinnitus group (21.8 vs. 8.0 %, P < 0.05), and the 5-HIAA level significantly correlated with the duration of tinnitus, NE and cortisol. Elevated stress-related hormones, as well as hearing loss, BDI, and BEPSI were the most related factors with tinnitus in multiple regression test with age adjustment. However, levels of stress-related hormones did not correlate with subjective measures including BDI, BEPSI and severity of tinnitus. In conclusion, blood stress hormones seemed to have some diagnostic and clinical value in patients with tinnitus, and serotonin is supposed to be the most important hormone in tinnitus. Further studies about the values of stress and stress hormones in tinnitus patients may lead to new approaches regarding diagnosis and clinical management of the disease.

  20. [Rethinking clinical significance of tear osmolarity measurement for dry eye diagnosis and therapeutic efficacy evaluation].

    PubMed

    Liang, Lingyi; Ke, Hongming; Liu, Zuguo

    2014-09-01

    Increased tear osmolarity is one of the core mechanisms of dry eye and has been considered as an important diagnostic criterion, if not"gold standard", of dry eye. However, recent studies showed the limitations of tear osmolarity measurement not only in the diagnosis, but also in the therapeutic efficacy evaluation of dry eye. The clinical significance of tear osmolarity measurement has become a hot topic of argument. Herein, we review the publications on this topic and try to find the underlying causes of such argument.

  1. Environmental pollution and DNA methylation: carcinogenesis, clinical significance, and practical applications.

    PubMed

    Cao, Yi

    2015-09-01

    Environmental pollution is one of the main causes of human cancer. Exposures to environmental carcinogens result in genetic and epigenetic alterations which induce cell transformation. Epigenetic changes caused by environmental pollution play important roles in the development and progression of environmental pollution-related cancers. Studies on DNA methylation are among the earliest and most conducted epigenetic research linked to cancer. In this review, the roles of DNA methylation in carcinogenesis and their significance in clinical medicine were summarized, and the effects of environmental pollutants, particularly air pollutants, on DNA methylation were introduced. Furthermore, prospective applications of DNA methylation to environmental pollution detection and cancer prevention were discussed.

  2. A Case of Traumatic Unilateral Internuclear Ophthalmoplegia: Clinical Significance of Susceptibility-Weighted Imaging

    PubMed Central

    Lee, Shin-heon; Park, Yong-sook; Kwon, Jeong-taik

    2016-01-01

    A 43-year-old man was admitted for head trauma after falling backward. The patient complained of diplopia. Unilateral internuclear ophthalmoplegia (INO) was diagnosed during the neurologic examination. Initially, no specific finding was shown on T2-weighted, T1-weighted, and fluid attenuated inversion recovery brain magnetic resonance image (MRI) or brain computed tomography (CT). However, susceptibility-weighted imaging (SWI) definitively demonstrated a tiny hemorrhage at the midline of the pontomesencephalic junction. The patient's symptom improved after 12 weeks. We discuss the clinical significance of SWI when traumatic INO due to a tiny hemorrhage is suspected. PMID:27857923

  3. [Clinical significance and distribution of BRCA genes mutation in sporadic high grade serous ovarian cancer].

    PubMed

    Liu, W L; Wang, Z Z; Zhao, J Z; Hou, Y Y; Wu, X X; Li, W; Dong, B; Tong, T T; Guo, Y J

    2017-01-25

    Objective: To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance. Methods: Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1) The BRCA genes were detected by next-generation sequencing (NGS) method. (2) The serum tumor markers included carcinoembryonic antigen (CEA), CA(125), CA(199), and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailed t-tests, Pearson's chi square test, Fisher's exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics (FIGO) stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM) . Results: (1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA(199), and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found (P>0.05), but the level of CA(125) was much higher in BRCA mutation group than that in controls (t=-3.536, P=0.003). Further linear regression analysis found that there was a significant linear correlation between CA(125) and HE4 group (r=0.494, P<0.01), and the same correlation as CEA and CA(199) group (r=0.897, P<0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA(+) and BRCA(-) group (P>0

  4. Macular dazzling test on normal subjects.

    PubMed Central

    Gomez-Ulla, F; Louro, O; Mosquera, M

    1986-01-01

    The macular dazzling test was performed on 240 healthy eyes, classified into six groups according to the ages of the subjects. The test was used to assess both long distance and short distance vision with a simultaneous study of the influence of mydriasis and miosis. The MDT is a test easy to perform, requires a minimum of co-operation by the subject, and gives repeatable results. The MDT values increase significantly as the age of the subject increases. The sex of the subject has no influence on it, and there are no significant differences between a subject's right and left eyes. Mydriasis does not affect the MDT, but miosis reduces the recovery period. All the values are statistically greater for long distance vision than for short distance vision. PMID:3954979

  5. Characterisation of a C1qtnf5 Ser163Arg Knock-In Mouse Model of Late-Onset Retinal Macular Degeneration

    PubMed Central

    Shu, Xinhua; Luhmann, Ulrich F. O.; Aleman, Tomas S.; Barker, Susan E.; Lennon, Alan; Tulloch, Brian; Chen, Mei; Xu, Heping; Jacobson, Samuel G.; Ali, Robin; Wright, Alan F.

    2011-01-01

    A single founder mutation resulting in a Ser163Arg substitution in the C1QTNF5 gene product causes autosomal dominant late-onset retinal macular degeneration (L-ORMD) in humans, which has clinical and pathological features resembling age-related macular degeneration. We generated and characterised a mouse “knock-in” model carrying the Ser163Arg mutation in the orthologous murine C1qtnf5 gene by site-directed mutagenesis and homologous recombination into mouse embryonic stem cells. Biochemical, immunological, electron microscopic, fundus autofluorescence, electroretinography and laser photocoagulation analyses were used to characterise the mouse model. Heterozygous and homozygous knock-in mice showed no significant abnormality in any of the above measures at time points up to 2 years. This result contrasts with another C1qtnf5 Ser163Arg knock-in mouse which showed most of the features of L-ORMD but differed in genetic background and targeting construct. PMID:22110650

  6. Characterisation of a C1qtnf5 Ser163Arg knock-in mouse model of late-onset retinal macular degeneration.

    PubMed

    Shu, Xinhua; Luhmann, Ulrich F O; Aleman, Tomas S; Barker, Susan E; Lennon, Alan; Tulloch, Brian; Chen, Mei; Xu, Heping; Jacobson, Samuel G; Ali, Robin; Wright, Alan F

    2011-01-01

    A single founder mutation resulting in a Ser163Arg substitution in the C1QTNF5 gene product causes autosomal dominant late-onset retinal macular degeneration (L-ORMD) in humans, which has clinical and pathological features resembling age-related macular degeneration. We generated and characterised a mouse "knock-in" model carrying the Ser163Arg mutation in the orthologous murine C1qtnf5 gene by site-directed mutagenesis and homologous recombination into mouse embryonic stem cells. Biochemical, immunological, electron microscopic, fundus autofluorescence, electroretinography and laser photocoagulation analyses were used to characterise the mouse model. Heterozygous and homozygous knock-in mice showed no significant abnormality in any of the above measures at time points up to 2 years. This result contrasts with another C1qtnf5 Ser163Arg knock-in mouse which showed most of the features of L-ORMD but differed in genetic background and targeting construct.

  7. Clinical significance of home blood pressure measurements for the prevention and management of high blood pressure.

    PubMed

    Imai, Yutaka; Hosaka, Miki; Elnagar, Noha; Satoh, Michihiro

    2014-01-01

    1. Ambulatory blood pressure (ABP) monitoring (M) provides BP information at many points on any particular day during unrestricted routine daily activities, whereas home blood pressure (HBP) monitoring provides a lot of BP information obtained under fixed times and conditions over a long period of time, thus mean values of HBP provide high reproducibility, and thus an overall superiority compared with ABP.  2. HBP is at least equally or better able than ABP to predict hypertensive target organ damage and prognosis of cardiovascular disease.  3. HBPM allows for ongoing disease monitoring by patients, improves adherence to antihypertensive treatment, and can provide health-care providers with timely clinical data and direct and immediate feedback regarding diagnosis and treatment of hypertension.  4. HBPM provides BP information in relation to time; that is, BP in the morning, in the evening and at night during sleep, and it is an essential tool for the diagnosis of white-coat and masked hypertension.  5. HBPM yields minimal alerting affects and no or minimal placebo effect, and can therefore distinguish small, but significant, serial changes in BP. It is thus the most practical method for monitoring BP in the day-to-day management of hypertension. 6. The superiority of HBPM over ABPM and clinic BPM is apparent from almost all practical and clinical research perspectives.

  8. Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation.

    PubMed

    Viloria, Katrina; Hill, Natasha J

    2016-05-01

    Matricellular proteins influence wide-ranging fundamental cellular processes including cell adhesion, migration, growth and differentiation. They achieve this both through interactions with cell surface receptors and regulation of the matrix environment. Many matricellular proteins are also associated with diverse clinical disorders including cancer and diabetes. Alternative splicing is a precisely regulated process that can produce multiple isoforms with variable functions from a single gene. To date, the expression of alternate transcripts for the matricellular family has been reported for only a handful of genes. Here we analyse the evidence for alternative splicing across the matricellular family including the secreted protein acidic and rich in cysteine (SPARC), thrombospondin, tenascin and CCN families. We find that matricellular proteins have double the average number of splice variants per gene, and discuss the types of domain affected by splicing in matricellular proteins. We also review the clinical significance of alternative splicing for three specific matricellular proteins that have been relatively well characterised: osteopontin (OPN), tenascin-C (TNC) and periostin. Embracing the complexity of matricellular splice variants will be important for understanding the sometimes contradictory function of these powerful regulatory proteins, and for their effective clinical application as biomarkers and therapeutic targets.

  9. Clinical Significance of Community- and Healthcare-Acquired Carbapenem-Resistant Enterobacteriaceae Isolates

    PubMed Central

    Tang, Hung-Jen; Hsieh, Cheng-Fang; Chang, Ping-Chin; Chen, Jyh-Jou; Lin, Yu-Hsiu; Lai, Chih-Cheng; Chao, Chien-Ming; Chuang, Yin-Ching

    2016-01-01

    This study was conducted to investigate the clinical significance, manifestations, microbiological characteristics and outcomes of carbapenem-resistant Enterobacteriaceae (CRE) isolates, and compare the clinical features of community- and healthcare-acquired CRE isolates. A total of 78 patients were identified to have CRE. Klebsiella pneumoniae was the most common pathogens (n = 42, 53.8%), followed by Enterobacter cloacae (n = 24, 30.8%), and Escherichia coli (n = 11, 14.1%). Most of the patients acquired CRE from healthcare settings (n = 55, 70.5%), and other cases got CRE from community settings (n = 23, 29.5%). Nine cases (11.5%) were classified as CRE colonization. Among the remaining 69 cases of CRE infections, pneumonia (n = 28, 40.6%) was the most common type of infections, followed by urinary tract infection (n = 24, 34.8%), and intra-abdominal infection (n = 16, 23.2%). The patients acquired CRE from community settings were more likely to be elderly, female, and had more urinary tract infections than from healthcare settings. In contrast, the patients acquired CRE from healthcare settings had more intra-abdominal infections, intra-abdominal surgery, and presence of indwelling device than from community settings. In conclusion, community-acquired CRE are not rare, and their associated clinical presentations are different from healthcare-acquired CRE. PMID:26999356

  10. Clinical Significance of an Alloantibody against the Kell Blood Group Glycoprotein

    PubMed Central

    Mattaloni, Stella Maris; Arnoni, Carine; Céspedes, Rosario; Nonaka, Claudia; Trucco Boggione, Carolina; Luján Brajovich, Melina Eliana; Trejo, Andrea; Zani, Néstor; Biondi, Claudia Silvia; Castilho, Lilian; Cotorruelo, Carlos Miquel

    2017-01-01

    Background Kell null (K0) individuals can produce anti-Ku, an antibody against many epitopes in the Kell glycoprotein, after transfusion and/or pregnancy. Since sensitized K0 patients are rare, little is known about anti-Ku clinical relevance and in particular about its association to hemolytic disease of the fetus and newborn. Case Report This work describes a case of neonatal hyperbilirubinemia due to immune-mediated erythrocyte destruction by an alloantibody directed against the Kell glycoprotein. Serologic and molecular approaches identified an anti-Ku alloantibody in maternal serum. A homozygous IVS3 + 1g>a point mutation (KEL*02N.06 allele) was found to be responsible for the lack of Kell antigen expression in the mother's red blood cell and subsequent alloimmunization after a previous pregnancy. Even though in most cases Kell antibodies are clinically severe and may cause suppression of erythropoiesis, in our case the newborn had a moderate anemia and hyperbilirubinemia that was successfully treated with phototherapy without requiring exchange transfusion. Serological and molecular studies performed in the proband's family members allowed us to provide them with proper counseling regarding alloimmunization after transfusion and/or pregnancy. Conclusions This case enlarges the understanding of the clinical significance of alloantibodies against Kell blood group antigens.

  11. Detection methods and clinical significance of free peritoneal tumor cells found during colorectal cancer surgery.

    PubMed

    Sibio, Simone; Fiorani, Cristina; Stolfi, Carmine; Divizia, Andrea; Pezzuto, Roberto; Montagnese, Fabrizio; Bagaglini, Giulia; Sammartino, Paolo; Sica, Giuseppe Sigismondo

    2015-09-27

    Peritoneal washing is now part of the standard clinical practice in several abdominal and pelvic neoplasias. However, in colorectal cancer surgery, intra-peritoneal free cancer cells (IFCC) presence is not routinely investigated and their prognostic meaning is still unclear. When peritoneal washing results are positive for the presence of IFCC a worse outcome is usually expected in these colorectal cancer operated patients, but it what is not clear is whether it is associated with an increased risk of local recurrence. It is authors' belief that one of the main reasons why IFCC are not researched as integral part of the routine staging system for colon cancer is that there still isn't a diagnostic or detection method with enough sensibility and specificity. However, the potential clinical implications of a routine research for the presence IFCC in colon neoplasias are enormous: not only to obtain a more accurate clinical staging but also to offer different therapy protocols, based on the presence of IFCC. Based on this, adjuvant chemotherapy could be offered to those patients found to be positive for IFCC; also, protocols of proactive intraperitoneal chemotherapy could be applied. Although presence of IFCC appears to have a valid prognostic significance, further studies are needed to standardize detection and examination procedures, to determine if there are and which are the stages more likely to benefit from routine search for IFCC.

  12. Significance of Image Guidance to Clinical Outcomes for Localized Prostate Cancer

    PubMed Central

    Zhong, Qiuzi; Gao, Hong; Li, Gaofeng; Xiu, Xia; Wu, Qinhong; Li, Ming; Xu, Yonggang

    2014-01-01

    Purpose. To compare toxicity profiles and biochemical tumor control outcomes between patients treated with image-guided intensity-modulated radiotherapy (IG-IMRT) and non-IGRT intensity-modulated radiotherapy (IMRT) for clinically localized prostate cancer. Materials and Methods. Between 2009 and 2012, 65 patients with localized prostate cancer were treated with IG-IMRT. This group of patients was retrospectively compared with a similar cohort of 62 patients who were treated between 2004 and 2009 with IMRT to the same dose without image guidance. Results. The median follow-up time was 4.8 years. The rectal volume receiving ≥40 and ≥70 Gy was significantly lower in the IG-IMRT group. Grade 2 and higher acute and late GI and GU toxicity rates were lower in IG-IMRT group, but there was no statistical difference. No significant improvement in biochemical control at 5 years was observed in two groups. In a Cox regression analysis identifying predictors for PSA relapse-free survival, only preradiotherapy PSA was significantly associated with biochemical control; IG-IMRT was not a statistically significant indicator. Conclusions. The use of image guidance in the radiation of prostate cancer at our institute did not show significant reduction in the rates of GI and GU toxicity and did not improve the biochemical control compared with IMRT. PMID:25110701

  13. Perceptual learning in patients with macular degeneration.

    PubMed

    Plank, Tina; Rosengarth, Katharina; Schmalhofer, Carolin; Goldhacker, Markus; Brandl-Rühle, Sabine; Greenlee, Mark W

    2014-01-01

    Patients with age-related macular degeneration (AMD) or hereditary macular dystrophies (JMD) rely on an efficient use of their peripheral visual field. We trained eight AMD and five JMD patients to perform a texture-discrimination task (TDT) at their preferred retinal locus (PRL) used for fixation. Six training sessions of approximately one hour duration were conducted over a period of approximately 3 weeks. Before, during and after training twelve patients and twelve age-matched controls (the data from two controls had to be discarded later) took part in three functional magnetic resonance imaging (fMRI) sessions to assess training-related changes in the BOLD response in early visual cortex. Patients benefited from the training measurements as indexed by significant decrease (p = 0.001) in the stimulus onset asynchrony (SOA) between the presentation of the texture target on background and the visual mask, and in a significant location specific effect of the PRL with respect to hit rate (p = 0.014). The following trends were observed: (i) improvement in Vernier acuity for an eccentric line-bisection task; (ii) positive correlation between the development of BOLD signals in early visual cortex and initial fixation stability (r = 0.531); (iii) positive correlation between the increase in task performance and initial fixation stability (r = 0.730). The first two trends were non-significant, whereas the third trend was significant at p = 0.014, Bonferroni corrected. Consequently, our exploratory study suggests that training on the TDT can enhance eccentric vision in patients with central vision loss. This enhancement is accompanied by a modest alteration in the BOLD response in early visual cortex.

  14. Markers of Collagen Remodeling Detect Clinically Significant Fibrosis in Chronic Hepatitis C Patients

    PubMed Central

    Nielsen, Mette J.; Kazankov, Konstantin; Leeming, Diana J.; Karsdal, Morten A.; Krag, Aleksander; Barrera, Francisco; McLeod, Duncan; George, Jacob; Grønbæk, Henning

    2015-01-01

    Background and Aim Detection of advanced fibrosis (Metavir F≥3) is important to identify patients with a high urgency of antiviral treatments vs. those whose treatment could be deferred (F≤2). The aim was to assess the diagnostic value of novel serological extracellular matrix protein fragments as potential biomarkers for clinically significant and advanced fibrosis. Methods Specific protein fragments of matrix metalloprotease degraded type I, III, IV and VI collagen (C1M, C3M, C4M, C6M) and type III and IV collagen formation (Pro-C3 and P4NP7S) were assessed in plasma from 403 chronic hepatitis C patients by specific ELISAs. Patients were stratified according to Metavir Fibrosis stage; F0 (n = 46), F1 (n = 161), F2 (n = 95), F3 (n = 44) and F4 (n = 33) based on liver biopsy. Results Pro-C3 was significantly elevated in patients with significant fibrosis (≥F2) compared to F0-F1 (p<0.05), while the markers C3M, C4M, C6M and P4NP7S were significantly elevated in patients with advanced fibrosis (≥F3) compared to F0-F2 (p<0.05). C1M showed no difference between fibrosis stages. Using Receiver Operating Characteristics analysis, the best marker for detecting ≥F2 and ≥F3 was Pro-C3 with AUC = 0.75 and AUC = 0.86. Combination of Pro-C3 and C4M with age, BMI and gender in a multiple ordered logistic regression model improved the diagnostic value for detecting ≥F2 and ≥F3 with AUC = 0.80 and AUC = 0.88. Conclusion The Pro-C3 protein fragment provided clinically relevant diagnostic accuracy as a single marker of liver fibrosis. A model combining Pro-C3 and C4M along with patient’s age, body mass index and gender increased the diagnostic power for identifying clinically significant fibrosis. PMID:26406331

  15. Clinical significance of multidetector-row computed tomography in breast surgery.

    PubMed

    Doihara, Hiroyoshi; Fujita, Takeo; Takabatake, Daisuke; Takahashi, Hirotoshi; Ogasawara, Yutaka; Shimizu, Nobuyoshi

    2006-01-01

    Several reports support the association of higher ipsilateral breast tumor recurrence rates with positive or intermediate margins compared with negative pathologic margins. Precise evaluation of tumor extension and adequate surgical margin are important factors affecting tumor recurrence after breast-conserving surgery (BCS). Many studies have reported the utility of magnetic resonance imaging (MRI) for diagnosing the tumor extension of breast cancer, but few have evaluated the utility of multidetector-row computed tomography (MDCT). The results of this study show the clinical significance of MDCT for detecting cancer extension and demonstrate the clinical role of MDCT in BCS. Subjects comprised 136 patients grouped into two categories based on whether or not tumor extension was evaluated with MDCT preoperatively. The positive surgical margin rate and breast conservation rate were analyzed in each group and the clinical role of MDCT in BCS was evaluated. Moreover, evaluation of intraductal extension was done both with MDCT and histologically, and computed tomography (CT)-pathologic correlations were examined retrospectively. Finally, the margin-positive cases were analyzed in relation to their clinical characteristics. Sensitivity, specificity, positive predictive value, and negative predictive value for detection of the intraductal component were 71.8%, 85.7%, 82.1%, and 76.9%, respectively. The positive surgical margin rate and conservation rate are 7.46% and 81.9%, respectively, for those who were diagnosed with MDCT preoperatively; their corresponding rates without MDCT were 16.67% and 67.9%. Most margin-positive patients have remarkable lymphatic space invasion. Positive surgical margins were often recognized toward the nipple. For diagnosing the intraductal extension, MDCT shows sufficient diagnosability. Moreover, MDCT can provide appropriate information for the determination of adequate surgical margins and contribute to increases in breast conservation

  16. Clinical Significance of Pre- and Post-Transplant BAFF Levels in Kidney Transplant Recipients

    PubMed Central

    Min, Ji Won; Kim, Kyoung Woon; Kim, Bo-Mi; Doh, Kyoung Chan; Choi, Min Seok; Choi, Bum Soon; Park, Cheol Whee; Yang, Chul Woo; Kim, Yong-Soo

    2016-01-01

    It is well known that pre-transplant B cell activating factor (BAFF) levels are associated with the development of de novo anti-HLA antibodies and antibody mediated rejection post-transplant. However, the clinical significance of BAFF values at allograft rejection has not been determined. In this study, we investigated the clinical significance of pre-transplant BAFF level as well as post-transplant BAFF levels measured when indication biopsy was done. We checked for anti-HLA antibodies in 115 kidney transplant recipients who required allograft biopsy due to an increase in serum creatinine. With the same serum specimen, we measured BAFF levels, and in 78 of these patients, pre-transplant BAFF and anti-HLA antibody levels were detected as well. Patients in each group were divided into tertiles according to BAFF levels. We investigated the relationship between BAFF levels and the occurrence of anti-HLA antibodies. Pre-transplant BAFF levels showed significant association with pre-transplant sensitization, and also with early rejection (Tertile 3, 26.9% vs. Tertile 1, 11.5%; P<0.05). Post-transplant BAFF levels showed significant association with pre-transplant sensitization, but did not show association with anti-HLA antibodies and positive donor-specific antibodies at the time of biopsy. We did not find any association between post-transplant BAFF levels and allograft biopsy results, Banff scores and microvascular inflammation scores. In conclusion, pre-transplant BAFF levels are associated with pre-transplant sensitization and are useful in predicting allograft rejection. But post-transplant BAFF levels measured at the time of indication biopsy are not associated with the appearance of de novo HLA-DSA, allograft rejection, biopsy findings and other allograft outcomes. PMID:27631619

  17. Clinical Significance of Asthma Clusters by Longitudinal Analysis in Korean Asthma Cohort

    PubMed Central

    Kim, Sujeong; Yoon, Sun-young; Kwon, Hyouk-Soo; Chang, Yoon-Seok; Cho, You Sook; Jang, An-Soo; Park, Jung Won; Nahm, Dong-Ho; Yoon, Ho-Joo; Cho, Sang-Heon; Cho, Young-Joo; Choi, ByoungWhui; Moon, Hee-Bom; Kim, Tae-Bum

    2013-01-01

    Background We have previously identified four distinct groups of asthma patients in Korean cohorts using cluster analysis: (A) smoking asthma, (B) severe obstructive asthma, (C) early-onset atopic asthma, and (D) late-onset mild asthma. Methods and Results A longitudinal analysis of each cluster in a Korean adult asthma cohort was performed to investigate the clinical significance of asthma clusters over 12 months. Cluster A showed relatively high asthma control test (ACT) scores but relatively low FEV1 scores, despite a high percentage of systemic corticosteroid use. Cluster B had the lowest mean FEV1, ACT, and the quality of life questionnaire for adult Korean asthmatics (QLQAKA) scores throughout the year, even though the percentage of systemic corticosteroid use was the highest among the four clusters. Cluster C was ranked second in terms of FEV1, with the second lowest percentage of systemic corticosteroid use, and showed a marked improvement in subjective symptoms over time. Cluster D consistently showed the highest FEV1, the lowest systemic corticosteroid use, and had high ACT and QLQAKA scores. Conclusion Our asthma clusters had clinical significance with consistency among clusters over 12 months. These distinctive phenotypes may be useful in classifying asthma in real practice. PMID:24391784

  18. Lipoprotein Subfractions in Metabolic Syndrome and Obesity: Clinical Significance and Therapeutic Approaches

    PubMed Central

    Nikolic, Dragana; Katsiki, Niki; Montalto, Giuseppe; Isenovic, Esma R.; Mikhailidis, Dimitri P.; Rizzo, Manfredi

    2013-01-01

    Small, dense low density lipoprotein (sdLDL) represents an emerging cardiovascular risk factor, since these particles can be associated with cardiovascular disease (CVD) independently of established risk factors, including plasma lipids. Obese subjects frequently have atherogenic dyslipidaemia, including elevated sdLDL levels, in addition to elevated triglycerides (TG), very low density lipoprotein (VLDL) and apolipoprotein-B, as well as decreased high density lipoprotein cholesterol (HDL-C) levels. Obesity-related co-morbidities, such as metabolic syndrome (MetS) are also characterized by dyslipidaemia. Therefore, agents that favourably modulate LDL subclasses may be of clinical value in these subjects. Statins are the lipid-lowering drug of choice. Also, anti-obesity and lipid lowering drugs other than statins could be useful in these patients. However, the effects of anti-obesity drugs on CVD risk factors remain unclear. We review the clinical significance of sdLDL in being overweight and obesity, as well as the efficacy of anti-obesity drugs on LDL subfractions in these individuals; a short comment on HDL subclasses is also included. Our literature search was based on PubMed and Scopus listings. Further research is required to fully explore both the significance of sdLDL and the efficacy of anti-obesity drugs on LDL subfractions in being overweight, obesity and MetS. Improving the lipoprotein profile in these patients may represent an efficient approach for reducing cardiovascular risk. PMID:23507795

  19. Characterization of Change and Significance for Clinical Findings in Radiology Reports Through Natural Language Processing.

    PubMed

    Hassanpour, Saeed; Bay, Graham; Langlotz, Curtis P

    2017-01-03

    We built a natural language processing (NLP) method to automatically extract clinical findings in radiology reports and characterize their level of change and significance according to a radiology-specific information model. We utilized a combination of machine learning and rule-based approaches for this purpose. Our method is unique in capturing different features and levels of abstractions at surface, entity, and discourse levels in text analysis. This combination has enabled us to recognize the underlying semantics of radiology report narratives for this task. We evaluated our method on radiology reports from four major healthcare organizations. Our evaluation showed the efficacy of our method in highlighting important changes (accuracy 99.2%, precision 96.3%, recall 93.5%, and F1 score 94.7%) and identifying significant observations (accuracy 75.8%, precision 75.2%, recall 75.7%, and F1 score 75.3%) to characterize radiology reports. This method can help clinicians quickly understand the key observations in radiology reports and facilitate clinical decision support, review prioritization, and disease surveillance.

  20. Clinical Significance and Characterization of Streptococcus tigurinus Isolates in an Adult Population.

    PubMed

    Bourassa, Lori; Clarridge, J E

    2015-11-01

    Streptococcus tigurinus is a newly described member of the Streptococcus mitis group. Due to the difficulty in distinguishing viridans group streptococci (VGS) by phenotype, analysis of 16S rRNA sequences is necessary for the accurate identification of most species. Through a laboratory policy of analyzing all clinically significant isolates from the VGS group by16S rRNA gene sequencing, we identified 14 S. tigurinus isolates from 11 patients. The Vitek 2 system most commonly gave an excellent rating to an incorrect identification (e.g., Streptococcus mitis), as did matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) (e.g., Streptococcus oralis). S. tigurinus strains were recovered from numerous body sites, including the blood, peritoneal fluid, bone, synovial fluid, a perianal abscess, and an arm wound. Retrospective chart review indicated that most isolates were clinically significant, with bacteremia (n = 5), soft tissue infections (n = 3) osteomyelitis (n = 2), infected joint prosthesis (n = 2), and peritonitis (n = 2) being the most common, thus expanding the spectrum of disease associated with S. tigurinus.

  1. Detection and Classification of Cancer from Microscopic Biopsy Images Using Clinically Significant and Biologically Interpretable Features

    PubMed Central

    Kumar, Rajesh; Srivastava, Subodh

    2015-01-01

    A framework for automated detection and classification of cancer from microscopic biopsy images using clinically significant and biologically interpretable features is proposed and examined. The various stages involved in the proposed methodology include enhancement of microscopic images, segmentation of background cells, features extraction, and finally the classification. An appropriate and efficient method is employed in each of the design steps of the proposed framework after making a comparative analysis of commonly used method in each category. For highlighting the details of the tissue and structures, the contrast limited adaptive histogram equalization approach is used. For the segmentation of background cells, k-means segmentation algorithm is used because it performs better in comparison to other commonly used segmentation methods. In feature extraction phase, it is proposed to extract various biologically interpretable and clinically significant shapes as well as morphology based features from the segmented images. These include gray level texture features, color based features, color gray level texture features, Law's Texture Energy based features, Tamura's features, and wavelet features. Finally, the K-nearest neighborhood method is used for classification of images into normal and cancerous categories because it is performing better in comparison to other commonly used methods for this application. The performance of the proposed framework is evaluated using well-known parameters for four fundamental tissues (connective, epithelial, muscular, and nervous) of randomly selected 1000 microscopic biopsy images. PMID:27006938

  2. Clinical significance of pharmacogenomic studies in tardive dyskinesia associated with patients with psychiatric disorders

    PubMed Central

    Chang, Florence CF; Fung, Victor SC

    2014-01-01

    Pharmacogenomics is the study of the effects of genetic polymorphisms on medication pharmacokinetics and pharmacodynamics. It offers advantages in predicting drug efficacy and/or toxicity and has already changed clinical practice in many fields of medicine. Tardive dyskinesia (TD) is a movement disorder that rarely remits and poses significant social stigma and physical discomfort for the patient. Pharmacokinetic studies show an association between cytochrome P450 enzyme-determined poor metabolizer status and elevated serum antipsychotic and metabolite levels. However, few prospective studies have shown this to correlate with the occurrence of TD. Many retrospective, case-control and cross-sectional studies have examined the association of cytochrome P450 enzyme, dopamine (receptor, metabolizer and transporter), serotonin (receptor and transporter), and oxidative stress enzyme gene polymorphisms with the occurrence and severity of TD. These studies have produced conflicting and confusing results secondary to heterogeneous inclusion criteria and other patient characteristics that also act as confounding factors. This paper aims to review and summarize the pharmacogenetic findings in antipsychotic-associated TD and assess its clinical significance for psychiatry patients. In addition, we hope to provide insight into areas that need further research. PMID:25378945

  3. Serum BAFF and APRIL levels in patients with autoimmune hemolytic anemia and their clinical significance.

    PubMed

    Xu, Zi-Zhen; Zhao, Bing-Bing; Xiong, Hong; Wei, Bei-Wen; Wang, Ye-Fei

    2015-10-01

    B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) play crucial roles in B cell development, survival, and antibody production. Autoimmune hemolytic anemia (AIHA) is an acquired autoimmune disease that occurs when antibodies target autologous red blood cells. Here, we analyzed the serum levels of BAFF and APRIL and their respective clinical associations in patients with AIHA. Serum BAFF and APRIL levels in patients with AIHA were significantly higher (P < 0.01) than in healthy individuals. Serum BAFF and APRIL levels were significantly augmented in patients with lower hemoglobin levels (hemoglobin was <8 g/dL) and higher LDH activity (LDH > 480 IU/mL). Glucocorticoid treatment dramatically reduced serum levels of BAFF and APRIL. Thus, serum BAFF and APRIL levels may reflect the clinical activity of this disease. Our results indicate that analysis of serum concentrations of BAFF and APRIL potentially represents a useful tool for the assessment of AIHA disease activity and progression.

  4. [Prevalence and clinical significance of interactions drug-enteral nutrition in Intensive Care Units].

    PubMed

    Reis, Adriano Max Moreira; de Carvalho, Rhanna Emanuela Fontenele Lima; de Faria, Leila Marcia Pereira; de Oliveira, Regina Célia; Zago, Karine Santana de Azevedo; Cavelagna, Milena Ferreira; Silva, Adriano Gomes; Neto, Manoel Luis; Cassiani, Silvia Helena de Bortoli

    2014-01-01

    This is a multicenter, cross-sectional retrospective study, which aimed to determine the prevalence of interactions drug-enteral nutrition (EN) in Intensive Care Units (ICU) of seven teaching hospitals in Brazil, and to analyze the clinical significance of them. Information on medications and EN administered with 24 hours and 120 hours of hospitalization were collected. For identification of drug-EN interaction was employed software Drug Reax®. It was investigated 1.124 records. Of these, 320 patients, with 24 hours of hospitalization, were on EN, and 20 (6.3%) had drug-EN interaction. Of the 504 patients with 120 hours of hospitalization, 39 (7.7%) had drug-EN interaction. The most frequent drug-EN interactions of clinical significance were phenytoin-EN, warfarin-EN and levothyroxine-EN. Drug-EN interactions may interfere with the quality and cost effectiveness of care in ICU, so it is essential that the health team has knowledge about them.

  5. Clinical significance of incidental FDG uptake in the prostate gland detected by PET/CT

    PubMed Central

    Sahin, Ertan; Elboga, Umut; Kalender, Ebuzer; Basıbuyuk, Mustafa; Demir, Hasan Deniz; Celen, Yusuf Zeki

    2015-01-01

    The value of FDG-positron emission tomography/computed tomography (PET/CT) for detecting prostate cancer is unknown. We aimed to investigate the clinical value of incidental prostate FDG uptake on PET/CT scans. We reviewed 6128 male patients who underwent FDG-PET/CT scans and selected cases that reported hypermetabolic lesion in the prostate. The patients who have prior history of prostate carcinoma or prostate surgery were excluded from the study. We have analyzed the correlation between PET/CT findings and serum prostate-specific antigen (PSA) levels, imaging (USG), urological examinations and biopsy. Incidental 18F-FDG uptake of the prostate gland was observed in 79 patients (1.3%). While sixteen of them were excluded due to inadequate clinical data, the remaining 63 patients were included for further analysis. The patients were divided into two groups; 8 patients (12.7%) in the malignant group and 55 patients (87.3%) in the benign group. The SUVmax values were not significantly different between the two groups. In 6 (75%) patients with prostate cancer, FDG uptake was observed focally in the peripheral zone of the prostate glands. There was no significant correlation between the SUVmax and the PSA levels. Incidental 18F-FDG uptake in the prostate gland is a rare condition, but a substantial portion of it is associated with the cancer. Benign and malignant lesions of the prostate gland in FDG-PET/CT imaging could not be reliably distinguished. The peripheral focally FDG uptake of prostate glands should be further examined with the clinical and labaratory evaluations. PMID:26379847

  6. Clinical significance in oral cavity squamous cell carcinoma of pathogenic somatic mitochondrial mutations.

    PubMed

    Lai, Chih-Hsiung; Huang, Shiang-Fu; Liao, Chun-Ta; Chen, I-How; Wang, Hung-Ming; Hsieh, Ling-Ling

    2013-01-01

    Somatic mutations affecting the mitochondrial DNA (mtDNA) have been frequently observed in human cancers and proposed as important oncological biomarkers. However, the clinical significance of mtDNA mutations in cancer remains unclear. This study was therefore performed to explore the possible clinical use in assessing oral squamous cell carcinoma (OSCC) of pathogenic mtDNA mutations. The entire mitochondrial genome of 300 OSCC with their matched control DNAs was screened by direct sequencing and criteria were set to define a pathogenic somatic mutation. The patients' TP53 R72P genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The relationships between pathogenic somatic mutations, clinicopathogical features, TP53 R72P genotype and clinical prognosis were analyzed. Overall, 645 somatic mtDNA mutations were identified and 91 of these mutations were defined as pathogenic. About one quarter (74/300) of the OSCC tumor samples contained pathogenic mutations. Individuals with the TP53 R allele had a higher frequency of pathogenic somatic mutation than those with the PP genotype. Kaplan-Meier analysis indicated that TP53 R allele patients with pathogenic somatic mutations demonstrated a significant association with a poorer disease-free survival than other individuals (HR = 1.71; 95% CI, 1.15-2.57; p = 0.009) and this phenomenon still existed after adjusting for mtDNA haplogroup, tumor stage with treatment regimens, differentiation and age at diagnosis (HR = 1.59; 95% CI, 1.06-2.40; p = 0.03). Subgroup analyses showed that this phenomenon was limited to patients who received adjuvant radiotherapy/chemo-radiotherapy after surgery. The results strongly indicated that pathogenic mtDNA mutations are a potential prognostic marker for OSCCs. Furthermore, functional mitochondria may play an active role in cancer development and the patient's response to radiotherapy/chemo-radiotherapy.

  7. Wearable diagnostic system for age-related macular degeneration.

    PubMed

    Mohaghegh, N; Zadeh, E Ghafar; Magierowski, S

    2016-08-01

    This paper presents a novel head-mounted point-of-care diagnostic system for detection and continuous monitoring of Age-related Macular Degeneration (AMD). This wearable embedded open-source platform enables accurate monitoring of AMD by taking advantage of multiple standard graphical interface techniques such as Amsler Grid, Threshold Amsler Grid, Macular Computerized Psychophysical Test and Preferential Hyperacuity Perimeter (PHP). Here, we describe the proposed multi-Grid or so-called NGRID software and elaborate on the hardware prototype. This prototype includes a commercially available Oculus HMD incorporated with a single board computer. As the first step towards a fully integrated wearable system, this paper successfully proves the functionality of head-mounted graphical interface device ready for a live demonstration. Participants can experience this device and take a 10-minute AMD eye-exam. Furthermore, NGRID has been approved and permitted for an in-hospital clinical trial.

  8. Gene therapy in age related macular degeneration and hereditary macular disorders.

    PubMed

    Kinnunen, Kati; Yla-Herttuala, Seppo

    2012-06-01

    In ophthalmology, administration of the therapeutic agent can be difficult due to the tight barriers in the eye. Multiple injections may be needed to allow the therapeutic agent to reach adequate levels in retina and choroidea which may increase the risk of complications including endophthalmitis, cataract and haemorrhages. Optimal methods for the delivery of therapeutic agents to the posterior segments of the eye have not yet been developed. Gene therapy offers an alternative where the therapeutic protein or proteins can be induced in the target tissue for a prolonged period of time after a single injection. The eye is a promising target for gene therapy due to its small size and tissue boundaries preventing leakage of the therapeutic material to other tissues or systemic circulation. However, most of the work in ocular gene therapy is still at the preclinical phase; only three vectors have reached phase 1/2 clinical trials. This review summarizes basic principles and current status of gene therapy in age related macular degeneration and hereditary macular disorders.

  9. Evaluation of an oral telomerase activator for early age-related macular degeneration - a pilot study

    PubMed Central

    Dow, Coad Thomas; Harley, Calvin B

    2016-01-01

    Purpose Telomere attrition and corresponding cellular senescence of the retinal pigment epithelium contribute to the changes of age-related macular degeneration. Activation of the enzyme telomerase can add telomeric DNA to retinal pigment epithelium chromosomal ends and has been proposed as a treatment for age-related macular degeneration. We report the use of a small molecule, oral telomerase activator (TA)-65 in early macular degeneration. This study, focusing on early macular degeneration, provides a model for the use of TAs in age-related disease. Method Thirty-eight (38) patients were randomly assigned to a 1-year, double-blinded, placebo-controlled interventional study with arms for oral TA-65 or placebo. Macular functions via micro-perimetry were the primary measured outcomes. Results The macular function in the arm receiving the TA-65 showed significant improvement relative to the placebo control. The improvement was manifest at 6 months and was maintained at 1 year: macular threshold sensitivity (measured as average dB [logarithmic decibel scale of light attenuation]) improved 0.97 dB compared to placebo (P-value 0.02) and percent reduced thresholds lessened 8.2% compared to the placebo arm (P-value 0.04). Conclusion The oral TA significantly improved the macular function of treatment subjects compared to controls. Although this study was a pilot and a larger study is being planned, it is noteworthy in that it is, to our knowledge, the first randomized placebo-controlled study of a TA supplement. PMID:26869760

  10. Meta-Analysis of Prognostic and Clinical Significance of CD44v6 in Esophageal Cancer.

    PubMed

    Hu, Bangli; Luo, Wei; Hu, Rui-Ting; Zhou, You; Qin, Shan-Yu; Jiang, Hai-Xing

    2015-08-01

    CD44v6 is a cell adhesion molecule that plays an important role in the development and progression of esophageal cancer. However, the prognostic value and clinical significance of CD44v6 in esophageal cancer remains controversial. In the present study, we aimed to clarify these relationships through a meta-analysis.We performed a comprehensive search of studies from PubMed, EMBASE, Ovid library database, Google scholar, and Chinese National Knowledge Infrastructure databases that were published before June 2015. The odds ratio (OR) and pooled hazard ratio (HR) with the 95% confidence intervals (CI) were used to estimate the effects.Twenty-one studies including 1504 patients with esophageal cancer were selected to assess the prognostic value and clinical significance of CD44v6 in these patients. The results showed that the expression of CD44v6 was higher in esophageal cancer tissue than in normal colorectal tissue (OR=9.19, 95% CI=6.30-13.42). Moreover, expression of CD44v6 was higher in patients with lymphoid nodal metastasis, compared to those without (OR=6.91, 95% CI=4.81-9.93). The pooled results showed that CD44v6 was associated with survival in patients with esophageal cancer (HR = 2.47, 95% CI = 1.56-3.92). No significant difference in CD44v6 expression was found in patients with different histological types and tumor stages (both P>0.05). Moreover, no publication bias was found among the studies (all P > 0.05).This meta-analysis demonstrates that CD44v6 is associated with the metastasis of esophageal cancer and a poor prognosis, but is not associated with the histological types and tumor stages.

  11. Statins for age-related macular degeneration

    PubMed Central

    Gehlbach, Peter; Li, Tianjing; Hatef, Elham

    2016-01-01

    Background Age-related macular degeneration (AMD) is a progressive late onset disorder of the macula affecting central vision. Age-related macular degeneration is the leading cause of blindness in people over 65 years in industrialized countries. Recent epidemiologic, genetic, and pathological evidence has shown AMD shares a number of risk factors with atherosclerosis, leading to the hypothesis that statins may exert protective effects in AMD. Objectives The objective of this review was to examine the effectiveness of statins compared with other treatments, no treatment, or placebo in delaying the onset and progression of AMD. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 6), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2014), EMBASE (January 1980 to June 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to June 2014), PubMed (January 1946 to June 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov), and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 June 2014. Selection criteria We included randomized controlled trials (RCTs) that compared statins with other treatments, no treatment, or placebo in participants who were either susceptible to or diagnosed as having early stages of AMD. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently evaluated the search results against the selection criteria, abstracted data, and assessed risk of bias. We did not perform meta-analysis due to heterogeneity in the interventions and outcomes among the

  12. The genetics of inherited macular dystrophies

    PubMed Central

    Michaelides, M; Hunt, D; Moore, A

    2003-01-01

    The aim of this paper is to review current knowledge relating to the monogenic macular dystrophies, with discussion of currently mapped genes, chromosomal loci and genotype-phenotype relationships. Inherited systemic disorders with a macular dystrophy component will not be discussed. PMID:12960208

  13. The Incidence of Rhegmatogenous Retinal Complications in Macular Surgery After Prophylactic Preoperative Laser Retinopexy

    PubMed Central

    Tosi, Gian Marco; Esposti, Pierluigi; Romeo, Napoleone; Marigliani, Davide; Cevenini, Gabriele; Massimo, Patrizio; Nuti, Elisabetta; Esposti, Giulia; Ripandelli, Guido

    2016-01-01

    Abstract The aim of the study is to evaluate the clinical characteristics of intraoperative retinal breaks (RBs) and postoperative retinal detachment (RRD) in patients undergoing pars plana vitrectomy (PPV) for macular disorders, who were treated preoperatively with prophylactic peripheral laser retinopexy. This observational cohort study comprised of 254 patients who underwent macular surgery and were preoperatively subjected to prophylactic laser retinopexy anterior to the equator. The main outcome measures were the incidence and characteristics of intraoperative RBs and postoperative RRD. Intraoperative RBs occurred in 14 patients (5.5%). Ten patients presented a sclerotomy-related RB (3.9%) and 4 patients a nonsclerotomy-related RB (1.6%). Two patients showed postoperative RRD (0.7%). Neither of the 2 patients with postoperative RRD was macula-off at presentation: one of them was successfully operated on with scleral buckling and the other was managed by observation alone. A significantly increased risk for the intraoperative development of sclerotomy-related RB was found in 20-gauge PPV compared with 23/25-gauge PPV. Preoperative prophylactic peripheral laser retinopexy does not guarantee the prevention of intraopertaive RBs or postoperative RRD. However, it might prevent the involvement of the macula when RRD occurs postoperatively. PMID:27057893

  14. Macular Thickness in Subjective Memory Complaints and Mild Cognitive Impairment: A Non-Invasive Biomarker

    PubMed Central

    Giménez Castejón, Domingo; Dudekova, Miriama; Gómez Gallego, Maria; Lajara Blesa, Jerónimo

    2016-01-01

    ABSTRACT Alzheimer’s disease (AD) is the main cause of dementia worldwide, which implies an important socioeconomic problem in developed countries. Efforts to find biomarkers to diagnose AD have been intensified, especially, to detect cognitive impairment in its early stages, also known as mild cognitive impairment (MCI). Besides, there are individuals referring memory loss that is unnoticeable in the family environment and presenting normal neuropsychological tests. The former patients are included in a clinical picture that has been recently called subjective memory complaints (SMC). To achieve an early diagnosis, optical coherence tomography (OCT) has been used to measure macular thickness in patients diagnosed with MCI (supported by neuropsychological tests) and SMC (not based on neuropsychological battery). Statistically significant differences have been found in the macular thickness of the control group (274.96 ± 17.61 µm) and for both MCI (259.48 ± 22.39 µm) and SMC (261.45 ± 24.26 µm) patients. In the near future, OCT could become a reliable biomarker and a useful tool for AD screening as well as for the monitoring of the cognitive impairment associated with AD. PMID:27928377

  15. Prevalence, predictors and clinical significance of Blastocystis sp. in Sebha, Libya

    PubMed Central

    2013-01-01

    Background Blastocystis sp. has a worldwide distribution and is often the most common human intestinal protozoan reported in children and adults in developing countries. The clinical relevance of Blastocystis sp. remains controversial. This study was undertaken to determine the prevalence of Blastocystis infection and its association with gastrointestinal symptoms among outpatients in Sebha city, Libya. Methods A total of 380 stool samples were collected from outpatients attending the Central Laboratory in Sebha, Libya for routine stool examination. The presence of Blastocystis sp. was screened comparing light microscopy of direct smears against in vitro cultivation. Demographic and socioeconomic information were collected with a standardized questionnaire. Results The overall prevalence of Blastocystis infection was 22.1%. The prevalence was significantly higher among patients aged ≥18 years compared to those aged < 18 years (29.4% vs 9.9%; x2 = 19.746; P < 0.001), and in males compared to females (26.4% vs 17.5%; x2 = 4.374; P = 0.036). Univariate analysis showed significant associations between Blastocystis infection and the occupational status (P = 0.017), family size (P = 0.023) and educational level (P = 0.042) of the participants. Multiple logistic regression analysis confirmed that the age of ≥ 18 years (OR = 5.7; 95% CI = 2.21; 9.86) and occupational status (OR = 2.2; 95% CI = 1.02, 4.70) as significant predictors of Blastocystis infection among this population. In those who had only Blastocystis infection but no other gastrointestinal parasitic infections, the prevalence of gastrointestinal symptoms was higher compared to those without Blastocystis infection (35.3% vs 13.2%; x2 = 25.8; P < 0.001). The most common symptoms among these patients were abdominal pain (76.4%), flatulence (41.1%) and diarrhoea (21.5%). Conclusions Blastocystis sp. is prevalent and associated with

  16. Age and sex distribution of some retinal macular diseases: senile and presenile macular degeneration and central serous retinitis.

    PubMed

    Knave, B; Tengroth, B; Voss, M

    1984-01-01

    The age and sex distribution of senile macular degeneration (SMD) was investigated at the Low Vision Clinic in Stockholm. SMD increased with age and was found to be more common among women than men. This difference was not due to the fact that women live longer than men or related to women consulting ophthalmologists more often than men because of visual handicap. The age and sex distribution of presenile macular degeneration ( PSMD ) and central serous retinitis (CSR) was investigated at the Department of Ophthalmology of Falun Hospital. Also PSMD increased with age and was found to be more common among women than men, even if the sex difference was not as clear as for SMD. CSR was found to be more frequent at younger ages and, contrary to SMD and PSMD , more common among men. The reasons for these sex differences in frequencies of SMD, PSMD and CSR are not known.

  17. Visual function 5 years or more after macular translocation surgery for myopic choroidal neovascularisation and age-related macular degeneration

    PubMed Central

    Takeuchi, K; Kachi, S; Iwata, E; Ishikawa, K; Terasaki, H

    2012-01-01

    Purpose To evaluate the changes in the best-corrected visual acuity (BCVA) after 1 year and after ≥5 years after macular translocation for age-related macular degeneration (AMD) or myopic choroidal neovascularisation (mCNV). Methods The medical records of 61 consecutive patients who underwent macular translocation with 360° retinotomy for AMD (35 eyes) or mCNV (26 eyes) were reviewed. Overall, 40 patients, 17 mCNV and 23 AMD, were followed for at least 5 years. BCVA and area of the Goldmann visual field (VF) measured before, 12 months after surgery, and at the final visit. Results In the 23 AMD eyes followed for ≥5 years, the mean preoperative BCVA was 1.149±0.105 logMAR units, which significantly improved to 0.69±0.06 logMAR units at 1 year (P<0.001). This BCVA was maintained at 0.633±0.083 logMAR units on their final examination. In the 17 eyes with mCNV followed for ≥5 years, the mean preoperative BCVA was 1.083±0.119 logMAR units, which was significantly improved to 0.689±0.121 logMAR units at 1 year (P=0.001). This BCVA was maintained at 0.678±0.142 logMAR units on their final examination. The area of the VF was significantly decreased at 12 months and did not change significantly thereafter. Conclusions Our results show that macular translocation surgery significantly improves the BCVA and significantly decreases the VF area of eyes with mCNV or AMD after first 1 year. The BCVA and VF area do not change significantly from the values at 1 year for at least 5 years. PMID:22173070

  18. Clinical significance of noncalcified lung nodules in patients with breast cancer.

    PubMed

    Li, Feng; Armato, Samuel G; Giger, Maryellen L; MacMahon, Heber

    2016-09-01

    Patients with breast cancer are increasingly likely to have chest computed tomography (CT) performed. In many cases, small lung nodules will be detected, raising concern for metastases and causing considerable patient anxiety. The majority of these nodules, however, are benign, though the specific probability of malignancy is uncertain in any given case. Therefore, we analyzed the results of chest CT scans of a large number of patients with breast cancer, to determine characteristics and clinical significance of noncalcified lung nodules. 3313 patients were investigated, and 4889 CT scans from 1325 patients were retrospectively reviewed. Among the 1325 patients, 812 (59 %) had at least one noncalcified lung nodule, of which 330 (41 %) had malignant nodules, 197 (24 %) had large (≥10 mm) nodules, and 586 (72 %) had multiple nodules. Large nodules were more often malignant than benign (P < 0.001). In patients with multiple large nodules, the rate of malignancy rate was 83 %, and most of these were metastases. In the case of very small (2-4 mm) nodules, the malignancy rates for solitary and multiple nodules were 8 and 20 %, respectively. Lung metastases were more likely with breast cancer cell grade 3 (22 %) than grade 1-2 (10 %) (P < 0.001) and when patients were clinical stage 2-3 (14 %) than stage 0-1 (7.9 %) (P = 0.03). Lung metastases are highly likely in patients with multiple nodules greater than 10 mm. Higher cancer cell grades and clinical stage are also related to an increased likelihood of lung metastases. The great majority of small lung nodules in breast cancer patients are benign.

  19. Automatic segmentation of microcystic macular edema in OCT

    PubMed Central

    Lang, Andrew; Carass, Aaron; Swingle, Emily K.; Al-Louzi, Omar; Bhargava, Pavan; Saidha, Shiv; Ying, Howard S.; Calabresi, Peter A.; Prince, Jerry L.

    2014-01-01

    Microcystic macular edema (MME) manifests as small, hyporeflective cystic areas within the retina. For reasons that are still largely unknown, a small proportion of patients with multiple sclerosis (MS) develop MME—predominantly in the inner nuclear layer. These cystoid spaces, denoted pseudocysts, can be imaged using optical coherence tomography (OCT) where they appear as small, discrete, low intensity areas with high contrast to the surrounding tissue. The ability to automatically segment these pseudocysts would enable a more detailed study of MME than has been previously possible. Although larger pseudocysts often appear quite clearly in the OCT images, the multi-frame averaging performed by the Spectralis scanner adds a significant amount of variability to the appearance of smaller pseudocysts. Thus, simple segmentation methods only incorporating intensity information do not perform well. In this work, we propose to use a random forest classifier to classify the MME pixels. An assortment of both intensity and spatial features are used to aid the classification. Using a cross-validation evaluation strategy with manual delineation as ground truth, our method is able to correctly identify 79% of pseudocysts with a precision of 85%. Finally, we constructed a classifier from the output of our algorithm to distinguish clinically identified MME from non-MME subjects yielding an accuracy of 92%. PMID:25657884

  20. Idiopathic eruptive macular pigmentation with papillomatosis: Report of nine cases.

    PubMed

    Joshi, Rajiv

    2007-01-01

    Nine patients, seven males and two females aged 6-14 years, presented with extensive, asymptomatic, brown-black macules and mildly elevated, pigmented lesions of a few months' duration. The sites affected were the face, trunk and proximal extremities. The skin lesions were discrete and individual lesions were less than 2 cm in size. The clinical diagnoses rendered by the referring physicians were lichen planus pigmentosus, urticaria pigmentosa, erythema dyschromicum perstans and postinflammatory hyperpigmentation. Histology in all nine cases showed papillomatosis of the dermis with prominent pigmentation of the basal layer (pigmented papillomatosis) without any significant dermal inflammation. Two cases had spores of Pityrosporum ovale in the thickened horny layer, one of which also had, in addition, bacterial colonies in the stratum corneum. The pigmentation resolved on its own over several months. This presentation is similar to the previously described idiopathic eruptive macular pigmentation with the additional histological finding of papillomatosis that is being described for the first time and may be nosologically related to acanthosis nigricans and confluent and reticulate papillomatosis.

  1. Expression and clinical significance of obesity-associated gene STEAP4 in obese children.

    PubMed

    Xu, H M; Cui, Y Z; Wang, W G; Cheng, H X; Sun, Y J; Zhao, H Y; Yan, Y Q

    2016-10-05

    The aim of this study was to investigate the expression and clinical significance of the obesity-associated gene STEAP4 in obese children. Fifty-three obese children and 33 children with a standard body weight (control) from our hospital were recruited to this study. The expression of STEAP4 mRNA and protein in the adipose tissue were detected by reverse transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay, respectively, in order to analyze the relationship between STEAP4 mRNA and protein levels and blood pressure, blood lipid profile, blood glucose levels, and inflammation in obese children. Obese children showed significantly lower levels of STEAP4 mRNA and protein in the adipose tissue compared to the control subjects (P < 0.05). The obese subjects exhibited significantly higher diastolic blood pressure (DBP), systolic blood pressure (SBP), total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), fasting plasma glucose (FPG), interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels, and a significantly lower high-density lipoprotein (HDL) level, compared to the control subjects (P < 0.05). Correlation analysis revealed that STEAP4 expression was negatively correlated with the DBP, SBP, TC, TG, LDL, FPG, IL-6, and TNF-α levels, and was positively correlated with the HDL level (P < 0.05). In conclusion, the expression of STEAP4 was significantly downregulated in the adipose tissue of obese children and was closely related to the blood pressure, blood lipid, blood glucose, and inflammation in these patients; therefore, these results could provide a theoretical basis for the treatment of childhood obesity.

  2. Clinical significance of serum laminin and type-IV collagen levels in cutaneous melanoma patients.

    PubMed

    Tas, Faruk; Bilgin, Elif; Karabulut, Senem; Duranyildiz, Derya

    2016-07-01

    Laminin and type-IV collagen constitute a significant portion of the extracellular matrix. The objective of the present study was to evaluate whether the serum concentrations of laminin and type-IV collagen may serve as biomarkers for cutaneous melanoma. Sixty pathologically confirmed melanoma patients were enrolled in the study. Serum laminin and type-IV collagen levels were assessed using an ELISA. Thirty healthy controls were also examined. No significant differences in the baseline serum levels of laminin were identified between melanoma patients and healthy controls (P=0.45). However, the baseline serum levels of type-IV collagen were significantly elevated in melanoma patients compared with those in the control group (P<0.001). Clinical parameters, including patient age, gender, localization of lesion, histopathology, stage of disease, serum lactate dehydrogenase concentrations and responsiveness to chemotherapy were found not to be associated with the serum levels of laminin and type-IV collagen (P>0.05). Furthermore, the serum levels of laminin and type-IV collagen had no prognostic value regarding the outcome for melanoma patients (P=0.36 and P=0.26, respectively). While laminin levels showed no diagnostic value, the serum concentrations of type-IV collagen were indicated to serve as a diagnostic marker in patients with cutaneous melanoma. In conclusion, type-IV collagen levels may be used as a diagnostic marker for cutaneous melanoma, while being void of any prognostic value.

  3. The clinical significance of CDK1 expression in oral squamous cell carcinoma

    PubMed Central

    Chen, Xin; Chen, Qiao-Er; Wang, Yuan-Yin; Wang, Yin-Long; He, Jia-Cai; Zhou, Jian

    2015-01-01

    Objectives: To evaluate the clinical significance of cyclin-dependent kinase 1 (CDK1) in 77 oral squamous cell carcinomas (OSCC) using immunohistochemical methods. Study Design: Immunohistochemical expression of CDK1 was compared with various clinicopathological features in 77 OSCC and 60 controlled epithelia adjacent to the tumours. In addition, correlation of CDK1 expression and prognostic and the 5-year accumulative survival rate of OSCC were investigated. Results: The CDK1 protein was expressed in 52 cases of 77 tumor tissues (67.5%), compared with 21 cases of 60 controlled (35.0%). The expression of CDK1 was significantly correlated with the histological grade of OSCC (P<0.05). The CDK1 protein was over-expressed in recurrent tumors or in those with lymph node metastasis. Statistical analysis showed a significant reduction in the 5-year accumulative survival rate in CDK1 positive cases compared with CDK1 negative cases (P<0.05). Namely, the CDK1 positive patients had poor prognosis. Conclusions: The expression of CDK1 might serve as malignant degree and prognostic markers for the survival of OSCC. Key words:Cyclin-dependent kinase 1 (CDK1), oral squamous cell carcinoma (OSCC), immunohistochemistry, cell proliferation. PMID:25129248

  4. Clinical significance of serum laminin and type-IV collagen levels in cutaneous melanoma patients

    PubMed Central

    TAS, FARUK; BILGIN, ELIF; KARABULUT, SENEM; DURANYILDIZ, DERYA

    2016-01-01

    Laminin and type-IV collagen constitute a significant portion of the extracellular matrix. The objective of the present study was to evaluate whether the serum concentrations of laminin and type-IV collagen may serve as biomarkers for cutaneous melanoma. Sixty pathologically confirmed melanoma patients were enrolled in the study. Serum laminin and type-IV collagen levels were assessed using an ELISA. Thirty healthy controls were also examined. No significant differences in the baseline serum levels of laminin were identified between melanoma patients and healthy controls (P=0.45). However, the baseline serum levels of type-IV collagen were significantly elevated in melanoma patients compared with those in the control group (P<0.001). Clinical parameters, including patient age, gender, localization of lesion, histopathology, stage of disease, serum lactate dehydrogenase concentrations and responsiveness to chemotherapy were found not to be associated with the serum levels of laminin and type-IV collagen (P>0.05). Furthermore, the serum levels of laminin and type-IV collagen had no prognostic value regarding the outcome for melanoma patients (P=0.36 and P=0.26, respectively). While laminin levels showed no diagnostic value, the serum concentrations of type-IV collagen were indicated to serve as a diagnostic marker in patients with cutaneous melanoma. In conclusion, type-IV collagen levels may be used as a diagnostic marker for cutaneous melanoma, while being void of any prognostic value. PMID:27330797

  5. Refractory anemia with severe dysplasia: clinical significance of morphological features in refractory anemia.

    PubMed

    Matsuda, A; Jinnai, I; Yagasaki, F; Kusumoto, S; Minamihisamatsu, M; Honda, S; Murohashi, I; Bessho, M; Hirashima, K

    1998-04-01

    Refractory anemia (RA) in myelodysplastic syndromes (MDS) are very heterogeneous diseases regarding their morphology, clinical features and survival. We proposed the new designations 'RA with severe dysplasia (RASD)' and 'RA with minimal dysplasia (RAminiD)'. In our criteria, RASD is considered present if a bone marrow (BM) examination shows Pseudo-Pelger-Huet anomalies of mature neutrophils > or =3% and/or micromegakaryocytes (mMgk) of megakaryocytes > or =10% in RA patients. RAminiD is defined as RA cases other than RASD. After the reclassification of 58 primary RA patients, the group was composed of 45 RAminiD and 13 RASD patients. The blast percentage in the BM and the frequency of cytogenetic abnormalities observed in the RASD patients were intermediate between those in the RAminiD and RAEB patients. The analysis of survival curves revealed differences among the three groups; the RASD patients had lower survival probabilities than those of the RAminiD group, and significantly higher probabilities than those of the RAEB group. (RAminiD vs RASD, P=0.06; RASD vs RAEB, P=0.004.) Our data indicate that in RA patients, RASD is a distinct subset of RA with an unfavorable clinical outcome.

  6. Clinical features of congenital adrenal insufficiency including growth patterns and significance of ACTH stimulation test.

    PubMed

    Koh, Ji Won; Kim, Gu Hwan; Yoo, Han Wook; Yu, Jeesuk

    2013-11-01

    Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency.

  7. Clinical Features of Congenital Adrenal Insufficiency Including Growth Patterns and Significance of ACTH Stimulation Test

    PubMed Central

    Koh, Ji Won; Kim, Gu Hwan; Yoo, Han Wook

    2013-01-01

    Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency. PMID:24265530

  8. Clinical significance of sleep bruxism on several occlusal and functional parameters.

    PubMed

    Ommerborn, Michelle A; Giraki, Maria; Schneider, Christine; Fuck, Lars Michael; Zimmer, Stefan; Franz, Matthias; Raab, Wolfgang Hans-michael; Schaefer, Ralf

    2010-10-01

    The aim of this study was to evaluate the association between various functional and occlusal parameters and sleep bruxism. Thirty-nine (39) sleep bruxism patients and 30 controls participated in this investigation. The assessment of sleep bruxism was performed using the Bruxcore Bruxism-Monitoring Device (BBMD) combined with a new computer-based analyzing method. Sixteen functional and/or occlusal parameters were recorded. With a mean slide of 0.95 mm in the sleep bruxism group and a mean slide of 0.42 mm in the control group (Mann Whitney U test; p<0.003), results solely demonstrated a significant group difference regarding the length of a slide from centric occlusion to maximum intercuspation. The results suggest that the slightly pronounced slide could be of clinical importance in the development of increased wear facets in patients with current sleep bruxism activity. Following further evaluation including polysomnographic recordings, the BBMD combined with this new analyzing technique seems to be a clinically feasible instrument that allows the practitioner to quantify abrasion over a short period.

  9. The clinical significance and biological function of olfactomedin 4 in triple negative breast cancer.

    PubMed

    Xiong, Bin; Lei, Xuefeng; Zhang, Lei; Fu, Jia

    2017-02-01

    Olfactomedin 4 abnormal expression has been observed in several types of human cancer, but the status of olfactomedin 4 in triple negative breast cancer is still unknown. The aim of our study is to explore the clinical significance and biological function of olfactomedin 4 in triple negative breast cancer. The mRNA and protein expression of olfactomedin 4 in triple negative breast cancer tissues and cell lines was detected, and the correlation between olfactomedin 4 expression and clinicopathological factors was analyzed by immunohistochemistry. The biological function of olfactomedin 4 on tumor-metastasis was explored by Transwell migration assay and invasion assay in vitro. In our results, olfactomedin 4 mRNA and protein expression is decreased in triple-negative breast cancer tissues and cell lines. Olfactomedin 4 protein low-expression associated with lymph node metastasis, distant metastasis, clinical stage and poor prognosis of triple-negative breast cancer patients. Up-regulation of olfactomedin 4 suppresseed triple-negative breast cancer cells migration and invasion, and reduced cell metastasis-associated protein MMP 9 expression. In conclusion, olfactomedin 4 is a novel biomarker of triple-negative breast cancer for predicting prognosis and developing targeted molecular therapies.

  10. Clinical significance of cytomegalovirus infection in patients with inflammatory bowel disease.

    PubMed

    Garrido, Elena; Carrera, Elisa; Manzano, Rebeca; Lopez-Sanroman, Antonio

    2013-01-07

    Cytomegalovirus (CMV) infection is common in humans. The virus then enters a "latency phase" and can reactivate to different stimuli such as immunosuppression. The clinical significance of CMV infection in inflammatory bowel disease is different in Crohn's disease (CD) and ulcerative colitis (UC). CMV does not interfere in the clinical course of CD. However, CMV reactivation is frequent in severe or steroid-resistant UC. It is not known whether the virus exacerbates the disease or simply appears as a bystander of a severe disease. Different methods are used to diagnose CMV colitis. Diagnosis is classically based on histopathological identification of viral-infected cells or CMV antigens in biopsied tissues using haematoxylin-eosin or immunohistochemistry, other tests on blood or tissue samples are currently being investigated. Polymerase chain reaction performed in colonic mucosa has a high sensitivity and a positive result could be associated with a worse prognosis disease; further studies are needed to determine the most appropriate strategy with positive CMV-DNA in colonic mucosa. Specific endoscopic features have not been described in active UC and CMV infection. CMV colitis is usually treated with ganciclovir for several weeks, there are different opinions about whether or not to stop immunosuppressive therapy. Other antiviral drugs may be used. Multicenter controlled studies would needed to determine which subgroup of UC patients would benefit from early antiviral treatment.

  11. Are all significant P values created equal? The analogy between diagnostic tests and clinical research.

    PubMed

    Browner, W S; Newman, T B

    1987-05-08

    Just as diagnostic tests are most helpful in light of the clinical presentation, statistical tests are most useful in the context of scientific knowledge. Knowing the specificity and sensitivity of a diagnostic test is necessary, but insufficient: the clinician must also estimate the prior probability of the disease. In the same way, knowing the P value and power, or the confidence interval, for the results of a research study is necessary but insufficient: the reader must estimate the prior probability that the research hypothesis is true. Just as a positive diagnostic test does not mean that a patient has the disease, especially if the clinical picture suggests otherwise, a significant P value does not mean that a research hypothesis is correct, especially if it is inconsistent with current knowledge. Powerful studies are like sensitive tests in that they can be especially useful when the results are negative. Very low P values are like very specific tests; both result in few false-positive results due to chance. This Bayesian approach can clarify much of the confusion surrounding the use and interpretation of statistical tests.

  12. Macular thickness in healthy Saudi adults

    PubMed Central

    Al-Zamil, Waseem M.; Al-Zwaidi, Fahad M.; Yassin, Sanaa A.

    2017-01-01

    Objectives: To determine the macular thickness in the eyes of healthy Saudi adults using spectral-domain optical coherence tomography (SD-OCT). Methods: This is a prospective, cross-sectional study, including 158 healthy participants between August and December 2015. Mean subject age was 29.9 ± 7.85 years old. All participants underwent full ophthalmic evaluation, including SD-OCT imaging, and axial length measurement. Data from the right eye were included. Mean retinal thickness was determined. Correlations between retinal thickness and gender, age, axial length, and spherical equivalence were analyzed. Results: Mean central retinal thickness was 244.76 ± 23.62 µm, mean axial length was 23.8 ± 1.062 mm (range: 20.5-29 mm) and mean spherical equivalent was -0.31 ± 1.75 diopters (D) (range: -5.50 to +4.25 D). Central subfield (CSF) thickness and foveal volume were significantly lower in women than in men (both p<0.001). Data from the various age groups did not show statistically significant differences in the CSF thickness (p=0.389) or foveal volume (p=0.341). A positive correlation between CSF thickness and axial length (p<0.001) was observed. Conclusion: The normal macular thickness values in healthy Saudi individuals is different from that reported in other ethnic groups, as obtained by SD-OCT. Saudi men had thicker CSF than Saudi women and axial length was positively correlated to the central foveal thickness. PMID:28042632

  13. Assessment of clinical significance of anti-Ge in an untransfused man

    SciTech Connect

    Pearson, H.A.; Richards, V.L.; Wylie, B.R.; Bruce, D.; Watt, J.M.; Wilkie, D.; Kronenberg, H. )

    1991-03-01

    A 19-year-old, untransfused Melanesian man from Papua New Guinea was admitted to the hospital for repair of an atrial septal defect. His serum contained an alloantibody that reacted strongly on the indirect antiglobulin test and was identified as anti-Ge. Gerbich-negative blood was transfused following urgent surgery. A 51Cr red cell survival study performed 2 weeks after surgery yielded zero survival of Gerbich-positive cells after 24 hours. A monocyte-driven, antibody-dependent, cell-mediated cytotoxicity assay performed on both pretransfusion and posttransfusion serum samples and on concentrated serum showed less than 1 percent specific lysis of Gerbich-positive cells. This did not correlate with the indication of clinical significance predicted by the 51Cr study. Red cell adherence and phagocytosis, not evident in a monocyte monolayer assay using native serum, were demonstrable in 16 percent of monocytes by the use of concentrated serum.

  14. Trombone tongue: a new clinical sign for significant medullary compression at the craniovertebral junction. Case report.

    PubMed

    Lee, Cheong H; Casey, Adrian T H; Allibone, James B; Chelvarajah, Ramesh

    2006-12-01

    The authors describe a previously unreported clinical sign that may indicate the onset of significant compression of the medulla oblongata in cases of craniovertebral junction abnormalities. This 17-year-old boy presented with mild bilateral leg weakness. Imaging studies revealed severe basilar invagination and a marked Chiari malformation. While awaiting surgery, his tongue developed an involuntary constant protrusion-intrusion repetitive motion. The onset of this so-named "trombone tongue" sign was followed shortly afterward by rapidly progressive spastic tetraparesis. After the authors performed a transmaxillary clivectomy, foramen magnum decompression, and occipitocervical fusion, they noted that the abnormal tongue motion promptly resolved and the tetraparesis gradually improved. The authors discuss their current understanding of the central control of tongue movements and present a hypothesis on the pathogenesis of trombone tongue based on the neuroanatomical basis of another abnormal tongue movement sign, lingual myoclonus.

  15. WW domain-containing oxidoreductase's role in myriad cancers: clinical significance and future implications.

    PubMed

    Gardenswartz, Aliza; Aqeilan, Rami I

    2014-03-01

    The WW domain-containing oxidoreductase (WWOX) gene, encodes a tumor suppressor located on 16q23.1, spanning FRA16D, one of the most active common fragile sites in the human genome, that is altered in numerous types of cancer. WWOX's alteration in these myriad cancers is due to disparate mechanisms including loss of heterozygosity, homozygous deletion and epigenetic changes. In vitro, WWOX has been found to be reduced or absent in numerous cancer cell lines and WWOX restoration has been found to inhibit tumor cell growth and invasion. Wwox knockout mice developed femoral focal lesions resembling osteosarcomas within one month of their life and aging Wwox heterozygous mice have an increased incidence of spontaneous lung and mammary tumors as well as B-cell lymphomas. We herein review WWOX's role that has been unearthed thus far in different types of malignancies, its clinical significance and future implications.

  16. Clinical significance of in vivo cytarabine-induced gene expression signature in AML.

    PubMed

    Lamba, Jatinder K; Pounds, Stanley; Cao, Xueyuan; Crews, Kristine R; Cogle, Christopher R; Bhise, Neha; Raimondi, Susana C; Downing, James R; Baker, Sharyn D; Ribeiro, Raul C; Rubnitz, Jeffrey E

    2016-01-01

    Despite initial remission, ∼60-70% of adult and 30% of pediatric patients experience relapse or refractory AML. Studies so far have identified base line gene expression profiles of pathogenic and prognostic significance in AML; however, the extent of change in gene expression post-initiation of treatment has not been investigated. Exposure of leukemic cells to chemotherapeutic agents such as cytarabine, a mainstay of AML chemotherapy, can trigger adaptive response by influencing leukemic cell transcriptome and, hence, development of resistance or refractory disease. It is, however, challenging to perform such a study due to lack of availability of specimens post-drug treatment. The primary objective of this study was to identify in vivo cytarabine-induced changes in leukemia cell transcriptome and to evaluate their impact on clinical outcome. The results highlight genes relevant to cytarabine resistance and support the concept of targeting cytarabine-induced genes as a means of improving response.

  17. Role of multifaceted regulators in cancer glucose metabolism and their clinical significance

    PubMed Central

    Zhao, Luqing; Mao, Yitao; Zhao, Yuelong; Cao, Ya; Chen, Xiang

    2016-01-01

    Aberrant glucose metabolism, “aerobic glycolysis” or “Warburg effect”, is a hallmark of human cancers. There is a cluster of “multifaceted regulators”, which plays a pivotal role in the regulation of glucose metabolism. They can not only modulate the activities of specific enzymes, but also act as transcriptional activators to regulate the expression of metabolism related genes. Additionally, they can crosstalk with other key factors involved in glucose metabolism and work together to initiate multiple oncogenic processes. These “multifaceted regulators”, especially p53, HIF-1, TIGAR and microRNA, will be focused in this review. And we will comprehensively illustrate their regulatory effects on cancer glucose metabolism, and further elaborate on their clinical significance. In-depth elucidation the role of “multifaceted regulators” in cancer glucose metabolism will provide us novel insights in cancer research field and offer promising therapeutic targets for anti-cancer therapies. PMID:26934324

  18. Perspectives on the clinical significance of functional pain syndromes in children

    PubMed Central

    Basch, Molly C; Chow, Erika T; Logan, Deirdre E; Schechter, Neil L; Simons, Laura E

    2015-01-01

    Functional pain syndromes (FPS) characterize a subset of individuals who experience pain and related symptoms and disability without clear structural or disease etiology. In the pediatric population, FPS hold high clinical importance due to significant prevalence rates and potential to persist into adulthood. Although extensive research has been executed to disambiguate FPS, the syndromes that fall within its spectrum remain conceptually complex and sometimes ill-defined. This paper provides an overview of available research on the classification and multifaceted etiology of FPS in youth and their effects on interpersonal, psychological, and familial function. Vital aspects of a successful multidisciplinary approach to treating this population are described; however, it is evident that future research requires more longitudinal studies. PMID:26504406

  19. Paraneoplastic syndromes in patients with laryngeal neuroendocrine carcinomas: clinical manifestations and prognostic significance.

    PubMed

    Ferlito, Alfio; Rinaldo, Alessandra; Bishop, Justin A; Hunt, Jennifer L; Vander Poorten, Vincent; Williams, Michelle D; Triantafyllou, Asterios; Devaney, Kenneth O; Gnepp, Douglas R; Kusafuka, Kimihide; Halmos, Gyorgy B; Westra, William H; Takes, Robert P; Thompson, Lester D R

    2016-03-01

    Paraneoplastic syndromes are associated with a variety of malignant neoplasms and are systemic and non-metastatic manifestations that develop in a minority of cancer patients. This review examines all published cases of paraneoplastic syndromes associated with neuroendocrine carcinomas of the larynx. There are a total of ten patients reported with paraneoplastic syndromes associated with laryngeal neuroendocrine carcinomas in the literature. Of these, nine died and the tenth is alive with liver metastases. There were five cases of small-cell neuroendocrine carcinoma, four cases of moderately differentiated neuroendocrine carcinoma, and one case of well-differentiated neuroendocrine carcinoma associated with paraneoplastic syndromes. As these syndromes have significant clinical relevance, physicians should be aware of the possible presence of paraneoplastic syndromes in the diagnostic process of patients with neuroendocrine carcinoma of the larynx.

  20. [Viridans streptococci isolated from cerebrospinal fluid. Clinical significance of 9 cases].

    PubMed

    Alba, D; Guerra, A; Peña, P; Molina, F

    1997-02-01

    Viridans streptococci (VS) are often isolated from cerebrospinal fluid (CSF). However, the significance of such isolates is poorly understood. In the present study we carry out a retrospective analysis of 9 patients in whom VS were isolated from CSF during a 1-year period at La Paz Hospital. Two patients (22.2%) had meningitis diagnosed through clinical, laboratory and bacteriologic findings. Both patients had predisposition diseases (previous difficult spinal tap, ventriculo-peritoneal shunt). The other isolations were considered as contaminants. Three patients (33.3%) with no VS meningitis had other different serious disease (sepsis without bacteriologic confirmation). VS are isolated with relative frequency from CSF, although they cause meningitis in less than one-quarter of the cases (those who have a predisposition disease). In the other cases, VS are isolated as contaminants of CSF and other disease should be search as cause of patient symptoms.

  1. The clinical significance of small copy number variants in neurodevelopmental disorders

    PubMed Central

    Asadollahi, Reza; Oneda, Beatrice; Joset, Pascal; Azzarello-Burri, Silvia; Bartholdi, Deborah; Steindl, Katharina; Vincent, Marie; Cobilanschi, Joana; Sticht, Heinrich; Baldinger, Rosa; Reissmann, Regina; Sudholt, Irene; Thiel, Christian T; Ekici, Arif B; Reis, André; Bijlsma, Emilia K; Andrieux, Joris; Dieux, Anne; FitzPatrick, David; Ritter, Susanne; Baumer, Alessandra; Latal, Beatrice; Plecko, Barbara; Jenni, Oskar G; Rauch, Anita

    2014-01-01

    Background Despite abundant evidence for pathogenicity of large copy number variants (CNVs) in neurodevelopmental disorders (NDDs), the individual significance of genome-wide rare CNVs <500 kb has not been well elucidated in a clinical context. Methods By high-resolution chromosomal microarray analysis, we investigated the clinical significance of all rare non-polymorphic exonic CNVs sizing 1–500 kb in a cohort of 714 patients with undiagnosed NDDs. Results We detected 96 rare CNVs <500 kb affecting coding regions, of which 58 (60.4%) were confirmed. 6 of 14 confirmed de novo, one of two homozygous and four heterozygous inherited CNVs affected the known microdeletion regions 17q21.31, 16p11.2 and 2p21 or OMIM morbid genes (CASK, CREBBP, PAFAH1B1, SATB2; AUTS2, NRXN3, GRM8). Two further de novo CNVs affecting single genes (MED13L, CTNND2) were instrumental in delineating novel recurrent conditions. For the first time, we here report exonic deletions of CTNND2 causing low normal IQ with learning difficulties with or without autism spectrum disorder. Additionally, we discovered a homozygous out-of-frame deletion of ACOT7 associated with features comparable to the published mouse model. In total, 24.1% of the confirmed small CNVs were categorised as pathogenic or likely pathogenic (median size 130 kb), 17.2% as likely benign, 3.4% represented incidental findings and 55.2% remained unclear. Conclusions These results verify the diagnostic relevance of genome-wide rare CNVs <500 kb, which were found pathogenic in ∼2% (14/714) of cases (1.1% de novo, 0.3% homozygous, 0.6% inherited) and highlight their inherent potential for discovery of new conditions. PMID:25106414

  2. Clinical significance of COX-2, GLUT-1 and VEGF expressions in endometrial cancer tissues

    PubMed Central

    Ma, Xiaoping; Hui, Yuzuo; Lin, Li; Wu, Yu; Zhang, Xian; Liu, Peishu

    2015-01-01

    Objective: To analyze the clinical significance of COX-2, GLUT-1 and VEGF expressions in endometrial cancer tissues. Methods: One hundred and eight tissue samples from the patients with endometrial cancer enrolled in our hospital from August 2011 to July 2014 were selected, including 60 normal tissue samples (normal group), 60 neoplastic tissue samples (neoplastic group) and 60 cancer tissue samples (cancer group). All the samples were subjected to immunohistochemical assay to detect the expressions of COX-2, GLUT-1 and VEGF. The clinical data were also investigated for correlation analysis. Results: The positive rates of COX-2 in normal group, neoplastic group and cancer groups were 3.3%, 21.7% and 55.0% respectively. The positive rates of GLUT-1 in normal group, neoplastic group and cancer groups were 3.3%, 25.0% and 70.0% respectively. The positive rates of VEGF in normal group, neoplastic group and cancer groups were 1.7%, 23.3% and 63.3% respectively. With increasing stage of such cancer, decreasing degree of differentiation and lymphatic metastasis, the positive expression rates of COX-2, GLUT-1 and VEGF proteins were raised significantly (P<0.05). Spearman’s correlation analysis showed that the expressions of COX-2 and GLUT-1 (r=0.207, P<0.05), COX-2 and VEGF (r=0.243, P<0.05), as well as GLUT-1 and VEGF (r=0.758, P<0.05) were positively correlated. Conclusion: COX-2, GLUT-1 and VEGF were highly prominent in endometrial cancer, especially in the patients with low degree of differentiation, late stage and metastasis. They functioned synergistically in the onset and progression of this cancer. PMID:26101475

  3. The clinical significance of platelet microparticle-associated microRNAs.

    PubMed

    Provost, Patrick

    2017-05-01

    Circulating blood platelets play a central role in the maintenance of hemostasis. They adhere to subendothelial extracellular matrix proteins that become exposed upon vessel wall damage, which is followed by platelet activation, further platelet recruitment, platelet aggregation and formation of an occlusive, or non-occlusive, platelet thrombus. Platelets host a surprisingly diverse transcriptome, which is comprised of ~9500 messenger RNAs (mRNAs) and different classes of non-coding RNAs, including microRNAs, as well as a significant repertoire of proteins that contribute to their primary (adhesion, aggregation, granule secretion) and alternative (RNA transfer, mRNA translation, immune regulation) functions. Platelets have the propensity to release microparticles (MPs; 0.1-1 μm in diameter) upon activation, which may mediate inflammatory responses and contribute to exacerbate inflammatory diseases and conditions. Carrying components of the platelets' cytoplasm, platelet MPs may exert their effects on recipient cells by transferring their content in platelet-derived bioactive lipid mediators, cytokines, mRNAs and microRNAs. Platelet MP-associated microRNAs may thus function also outside of platelets and play an important role in intercellular signaling and gene expression programming across the entire circulatory system. The role and importance of platelet MP-associated microRNAs in various aspects of biology and pathophysiology are increasingly recognized, and now provide the scientific basis and rationale to support further translational research and clinical studies. The clinical significance, pathophysiological role as well as the diagnostic and therapeutic potential of platelet MP-associated microRNAs in cardiovascular diseases, platelet transfusion and cancer will be discussed.

  4. Distinguishing between statistical significance and practical/clinical meaningfulness using statistical inference.

    PubMed

    Wilkinson, Michael

    2014-03-01

    Decisions about support for predictions of theories in light of data are made using statistical inference. The dominant approach in sport and exercise science is the Neyman-Pearson (N-P) significance-testing approach. When applied correctly it provides a reliable procedure for making dichotomous decisions for accepting or rejecting zero-effect null hypotheses with known and controlled long-run error rates. Type I and type II error rates must be specified in advance and the latter controlled by conducting an a priori sample size calculation. The N-P approach does not provide the probability of hypotheses or indicate the strength of support for hypotheses in light of data, yet many scientists believe it does. Outcomes of analyses allow conclusions only about the existence of non-zero effects, and provide no information about the likely size of true effects or their practical/clinical value. Bayesian inference can show how much support data provide for different hypotheses, and how personal convictions should be altered in light of data, but the approach is complicated by formulating probability distributions about prior subjective estimates of population effects. A pragmatic solution is magnitude-based inference, which allows scientists to estimate the true magnitude of population effects and how likely they are to exceed an effect magnitude of practical/clinical importance, thereby integrating elements of subjective Bayesian-style thinking. While this approach is gaining acceptance, progress might be hastened if scientists appreciate the shortcomings of traditional N-P null hypothesis significance testing.

  5. Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation

    NASA Astrophysics Data System (ADS)

    Brivio, D.; Zygmanski, P.; Arnoldussen, M.; Hanlon, J.; Chell, E.; Sajo, E.; Makrigiorgos, G. M.; Ngwa, W.

    2015-12-01

    This work uses Monte Carlo radiation transport simulation to assess the potential benefits of gold nanoparticles (AuNP) in the treatment of neovascular age-related macular degeneration with stereotactic radiosurgery. Clinically, a 100 kVp x-ray beam of 4 mm diameter is aimed at the macula to deliver an ablative dose in a single fraction. In the transport model, AuNP accumulated at the bottom of the macula are targeted with a source representative of the clinical beam in order to provide enhanced dose to the diseased macular endothelial cells. It is observed that, because of the AuNP, the dose to the endothelial cells can be significantly enhanced, allowing for greater sparing of optic nerve, retina and other neighboring healthy tissue. For 20 nm diameter AuNP concentration of 32 mg g-1, which has been shown to be achievable in vivo, a dose enhancement ratio (DER) of 1.97 was found to be possible, which could potentially be increased through appropriate optimization of beam quality and/or AuNP targeting. A significant enhancement in dose is seen in the vicinity of the AuNP layer within 30 μm, peaked at the AuNP-tissue interface. Different angular tilting of the 4 mm beam results in a similar enhancement. The DER inside and in the penumbra of the 4 mm irradiation-field are almost the same while the actual delivered dose is more than one order of magnitude lower outside the field leading to normal tissue sparing. The prescribed dose to macular endothelial cells can be delivered using almost half of the radiation allowing reduction of dose to the neighboring organs such as retina/optic nerve by 49% when compared to a treatment without AuNP.

  6. Relationship between macular pigment and visual function in subjects with early age-related macular degeneration

    PubMed Central

    Nolan, John M; Peto, Tunde; Stack, Jim; Leung, Irene; Corcoran, Laura; Beatty, Stephen

    2017-01-01

    Purpose To investigate the relationship between macular pigment (MP) and visual function in subjects with early age-related macular degeneration (AMD). Methods 121 subjects with early AMD enrolled as part of the Central Retinal Enrichment Supplementation Trial (CREST; ISRCTN13894787) were assessed using a range of psychophysical measures of visual function, including best corrected visual acuity (BCVA), letter contrast sensitivity (CS), mesopic and photopic CS, mesopic and photopic glare disability (GD), photostress recovery time (PRT), reading performance and subjective visual function, using the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25). MP was measured using customised heterochromatic flicker photometry. Results Letter CS, mesopic and photopic CS, photopic GD and mean reading speed were each significantly (p<0.05) associated with MP across a range of retinal eccentricities, and these statistically significant relationships persisted after controlling for age, sex and cataract grade. BCVA, NEI VFQ-25 score, PRT and mesopic GD were unrelated to MP after controlling for age, sex and cataract grade (p>0.05, for all). Conclusions MP relates positively to many measures of visual function in unsupplemented subjects with early AMD. The CREST trial will investigate whether enrichment of MP influences visual function among those afflicted with this condition. Trial registration number ISRCTN13894787. PMID:27091854

  7. The Clinical Significance of Interleukin–1 Receptor Antagonist +2018 Polymorphism in Rheumatoid Arthritis

    PubMed Central

    Ismail, Endom; Nofal, Omimah Khaled Jaber; Sakthiswary, Rajalingham; Shaharir, Syahrul Sazliyana; Sridharan, Radhika

    2016-01-01

    Objective Interleukin-1 receptor antagonist (IL-1Ra) acts as an inhibitor of IL-1; which is one of the culprit cytokines in rheumatoid arthritis (RA). Although +2018 polymorphism of IL-1Ra has been implicated in the pathogenesis of RA, its importance remains poorly understood. Hence, the purpose of this study was to determine the clinical significance of interleukin-1 receptor antagonist (IL-1Ra) +2018 polymorphism in RA. Methods Polymerase chain reaction (PCR) and sequencing were used to determine the genotypes of the IL-1Ra +2018 for 77 RA patients and 18 healthy controls. All RA patients were assessed for the disease activity score that includes 28 joints (DAS28) and radiographic disease damage based on Modified Sharp Score (MSS). Results The frequency of the T/T and C/T genotypes did not differ significantly (p = 0.893) between the RA patients and the controls. The C/T genotype had significantly higher mean disease activity (DAS 28) and disease damage (MSS) scores with p values of 0.017 and 0.004, respectively. Additionally, the ESR (erythrocyte sedimentation rate), CRP (C-reactive protein), the number of swollen and tender joints were higher for the C/T individuals. On multivariate analysis the CRP, swollen joint count and MSS remained significant with the following p values i.e. 0.045, 0.046 and less than 0.05. Conclusions C/T genotype of IL-1Ra +2018 prognosticates more aggressive disease in RA. PMID:27105431

  8. Clinical significance of Cox-2, Survivin and Bcl-2 expression in hepatocellular carcinoma (HCC).

    PubMed

    Yang, Yu; Zhu, Jiang; Gou, Hongfeng; Cao, Dan; Jiang, Ming; Hou, Mei

    2011-09-01

    Cox-2, Survivin and Bcl-2 are frequently overexpressed in numerous types of cancers. They are known to be the important regulators of apoptosis. This study was designed to investigate the correlation between the clinical characteristics and the expression of Cox-2, Survivin and Bcl-2 in hepatocellular carcinoma. A total of 63 postoperative hepatocellular carcinoma (HCC) samples, 10 adjacent non-tumor samples and 10 normal liver samples were immunochemically detected for the expression of Cox-2, Survivin and Bcl-2. A median follow-up of 4 years for the 63 HCC patients was conducted. Univariate tests and multivariate Cox regression were performed for statistical analysis. The Kaplan-Meier method was used to analyze the survival. Positive expression of Cox-2 (84.3%) and Survivin (77.8%) was detected significantly more frequently in the HCC samples than in the normal liver tissues (30% and 0, respectively). Bcl-2 was highly expressed in the adjacent non-tumor tissue. Cox-2 was positively correlative to Survivin. Survivin and Bcl-2 were significantly associated with the pathological grade of HCC (P<0.05). Expression of both Cox-2 and Survivin was significantly associated with the poor overall survival (OS) (P=0.0141, P=0.0039). Furthermore, multivariate analysis confirmed the independent prognostic value of Survivin expression, along with tumor size and hepatic function. Cox-2 and Survivin were highly expressed in the HCC tissue. Survivin and Bcl-2 were significantly associated with the pathological grade of HCC. The expression of Survivin was an independent prognostic factor for HCC after a hepatectomy. Treatment that inhibits Survivin may be a promising targeted approach in HCC.

  9. Clinical significance of putative markers of cancer stem cells in gastric cancer: A retrospective cohort study

    PubMed Central

    He, Du; Lu, Zheng-Hao; Liu, Kai; Zhang, Wei-Han; Wang, Wei; Li, Chang-Chun; Xue, Lian; Zhao, Lin-Yong; Yang, Kun; Liu, Jian-Ping; Zhou, Zong-Guang; Hu, Jian-Kun; Mo, Xian-Ming

    2016-01-01

    Cancer stem cells (CSCs) are thought as the source of tumor maintaining and many CSCs markers have been identified. Regarding the heterogeneity in gastric cancer (GC), TNM stage is not enough to accurately predict the prognosis. The aim of this study was to investigate the clinical significance of CSCs markers (Lgr5, Oct4, CD133, EpCAM, CD54 and Sox2) and establish a new model based on these markers to accurately predict prognosis of GC. We retrospectively enrolled 377 GC tissues from January 2006 to October 2012 to perform immunohistochemistry (IHC), and 93 pairs of GC tissues and corresponding adjacent normal gastric tissues to perform quantitative PCR (qPCR) from December 2011 to October 2012. The clinicopathological and follow-up characteristics were collected. In IHC, Oct4, CD133 and EpCAM were independently related to tumor progression, while Sox2 were associated with well or moderate differentiation (all p<0.05). Cox regression showed that Oct4-EpCAM was an independently prognostic factor, indicating that double low expression of Oct4-EpCAM group had significantly better prognosis than control group (p=0.035). Regarding qPCR, CD133 was an independent prognostic factor, showing that the prognosis of patients with CD133 high expression was significantly worse than that of patients with CD133 low expression (p<0.001). The prognostic prediction accuracy of nomogram based on Oct4-EpCAM expression in IHC was significantly better than TNM stage alone (p=0.003). Low expressions of Oct4-EpCAM in IHC and CD133 in qPCR were favorable prognostic factors in GC. The nomogram based on Oct4-EpCAM was valuable in prognostic prediction of GC patients. PMID:27557490

  10. Smoking as a risk factor for cystoid macular edema complicating intermediate uveitis

    PubMed Central

    Thorne, Jennifer E.; Daniel, Ebenezer; Jabs, Douglas A.; Kedhar, Sanjay R.; Peters, George B.; Dunn, James P.

    2008-01-01

    Purpose To describe risk factors for the presence of cystoid macular edema (CME) among patients presenting with intermediate uveitis. Design Cross-sectional study. Methods Setting: Single-center, academic practice. Study population: 208 patients with intermediate uveitis evaluated from 1984 through September 2006. Procedures: Clinical and demographic data were entered retrospectively into a database and analyzed. Outcome measures: Presence of CME at presentation to our clinic; risk factors for presenting with CME. Results Of the 208 patients, 74% had bilateral intermediate uveitis, yielding 363 affected eyes. 89 patients (43%) had CME in at least one eye at the time of presentation to our clinic. After controlling for potentially confounding variables including demographics, duration of disease, active intraocular inflammation, history of diabetes mellitus or hypertension, and presence of epiretinal membrane, actively smoking at presentation was associated with a 4-fold increased risk of CME at presentation versus never smoking (OR = 3.90, 95% CI: 1.43, 10.66, P = 0.008). Former smoking also appeared to increase the risk CME at presentation in the multivariate analysis, but the result was of borderline statistical significance (OR = 1.97; 95% CI: 0.99, 3.94, P = 0.055). After adjusting for confounding, there was a 4% increased risk of CME at presentation for each cigarette smoked per day (OR = 1.04, 95%CI: 1.01, 10.7, P = 0.005). Conclusions Cystoid macular edema was a common structural ocular complication observed in our cohort. Current smoking was associated with a dose-dependent increased risk of having CME at the time of presentation to our clinic. PMID:18321467

  11. Clinical significance of circulating dendritic cells in patients with systemic lupus erythematosus.

    PubMed Central

    Robak, E; Smolewski, P; Woźniacka, A; Sysa-Jedrzejowska, A; Robak, T

    2004-01-01

    Dendritic cells are a complex group of mainly bone-marrow-derived leukocytes that play a role in autoimmune diseases. The total number of circulating dendritic cells (tDC), and their plasmacytoid dendritic cell (pDC) and myeloid dendritic cell (mDC1 and mDC2) subpopulations were assessed using flow cytometry. The number of tDC and their subsets were significantly lower in systemic lupus erythematosus patients than in the control group. The count of tDC and their subsets correlated with the number of T cells. The number of tDC and pDC subpopulation were lower in the patients with lymphopenia and leukopenia than in the patients without these symptoms. Our data suggest that fluctuations in blood dendritic cell count in systemic lupus erythematosus patients are much more significant in pDC than in mDC, what may be caused by their migration to the sites of inflammation including skin lesions. Positive correlation between dendritic cell number and TCD4+, TCD8+ and CD19+ B cells, testify of their interactions and influence on SLE pathogenesis. The association between dendritic cell number and clinical features seems to be less clear. PMID:15223608

  12. Expression of O(6)-methylguanine DNA methyltransferase (MGMT) and its clinical significance in gastroenteropancreatic neuroendocrine neoplasm.

    PubMed

    Yang, Qiu-Chen; Wang, Yu-Hong; Lin, Yuan; Xue, Ling; Chen, Yuan-Jia; Chen, Min-Hu; Chen, Jie

    2014-01-01

    O(6)-methylguanine-DNA methyltransferase (MGMT) is a widespread DNA repair enzyme defending against mutation caused by guanine O(6)-alkylating agents. Until now, we know only little about the expression of MGMT in gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). To study the expression of MGMT and its clinical significance in GEP-NEN, 174 specimens of GEP-NEN were examined, of which 152 specimens came from The First Affiliated Hospital, Sun Yat-sen University during October 1995 to November 2013, 22 specimens came from Peking Union Medical College Hospital during September 2004 to April 2010. MGMT protein was detected with EnVision immunohistochemical staining method. Clinicopathological factors were also collected and analyzed. We observed that the overall expression rate of MGMT was 83.9%. Over expression of MGMT protein was not associated with sex, age, functional status, primary tumor location, grading, classification, TNM stage and metastasis (P > 0.05). Kaplan-Meier analysis revealed that there was no significant difference in survival between MGMT-positive and MGMT-negative tumors of GEP-NEN patients (χ(2) = 0.887, P = 0.346). In multivariate analyses carried out by Cox proportional hazards regression model, MGMT expression was also not an independent predictors of survival. These results demonstrated that MGMT protein was highly expressed in GEP-NEN. MGMT deficiency rate was similar in pancreatic NEN and in gastrointestinal NEN. MGMT expression was not correlated with prognosis of GEP-NEN.

  13. Clinical significance of serum vascular endothelial growth factor in young male asthma patients

    PubMed Central

    Lee, Hea Yon; Min, Kyung Hoon; Lee, Sang Min; Lee, Ji Eun; Rhee, Chin Kook

    2017-01-01

    Background/Aims Vascular endothelial growth factor (VEGF) is an important mediator of angiogenesis. However, little is known about the potential use of serum levels of VEGF as a biomarker for asthma. We investigated the differences in VEGF levels among normal controls, stable asthma patients, and those with exacerbation of acute asthma. All subjects were young males. Methods We measured VEGF levels in each patient group, and examined any serial changes in those with acute exacerbation. Results VEGF levels were significantly higher in stable asthmatic patients and even more so in acute asthmatic patients, compared to healthy controls. However, there was no correlation between VEGF levels and forced expiratory volume in 1 second in patients with stable asthma. In addition, there were no correlations between VEGF levels and asthma control test scores. In patients with acute exacerbation, VEGF levels significantly increased during the acute period; their levels decreased gradually at 7 and 14 days after treatment. Conclusions Compared to normal control patients, the serum levels of VEGF were elevated in stable asthma patients and even more elevated in patients with acute exacerbation. However, the role of VEGF as a biomarker in stable asthma is limited. In patients with acute exacerbation, VEGF levels were associated with clinical improvements. PMID:26996348

  14. Expression and clinical significance of matrix metalloproteinase-17 and -25 in gastric cancer

    PubMed Central

    WANG, YING; YU, SHI-JIE; LI, YAN-XIA; LUO, HE-SHENG

    2015-01-01

    The aim of the present study was to investigate the expression and clinicopathological features of matrix metalloproteinase 17 (MMP17; also known as MT4-MMP) and MMP25 (also known as MT6-MMP) in gastric cancer. Immunohistochemistry and reverse transcription-quantitative polymerase chain reaction were used to detect the expression of MMP17 and MMP25 in 42 cases of gastric carcinoma and normal tissues, and 40 cases of atrophic gastritis. The expression of MMP17 in the normal gastric and atrophic gastritis tissues was significantly lower than that in the gastric cancer tissues (P<0.05). The expression of MMP25 in the gastric cancer and atrophic gastritis tissues was markedly higher compared with the normal gastric tissues (P<0.05). The expression of MMP17 and MMP25 was significantly associated with the depth of tumor invasion, lymph node metastasis and serous membrane involvement (P<0.05), but not with patient age and gender, or lesion length, site and histological grade (P>0.05). Therefore, this indicates that the expression of MMP17 and MMP25 is increased with the degree of progress of gastric carcinoma. The detection of MMP17 and MMP25 expression may have clinical value in predicting the prognosis of patients with gastric cancer. PMID:25621036

  15. Clinical and biological significance of CXCR5 expressed by prostate cancer specimens and cell lines.

    PubMed

    Singh, Shailesh; Singh, Rajesh; Singh, Udai P; Rai, Shesh N; Novakovic, Kristian R; Chung, Leland W K; Didier, Peter J; Grizzle, William E; Lillard, James W

    2009-11-15

    Chemokines and chemokine receptors have been shown to be involved in metastatic process of prostate cancer (PCa). In this study, we show primary PCa tissues and cell lines (LNCaP and PC3) express CXCR5, a specific chemokine receptor for CXCL13. Expression of CXCR5 was significantly higher (p < 0.001) in PCa cases than compared to normal match (NM) tissues. CXCR5 intensity correlated (R(2) = 0.97) with Gleason score. While prostate tumor tissues with Gleason scores >or= 7, displayed predominantly nuclear CXCR5 expression patterns, PCa specimens with Gleason scores significantly more CXCR5 than normal prostatic epithelial cells (PrECs), and CXCR5 expression was distributed among intracellular and extracellular compartments. Functional in vitro assays showed higher migratory and invasive potentials toward CXCL13, an effect that was mediated by CXCR5. In both PCa cell lines, CXCL13 treatment increased the expression of collagenase-1 or matrix metalloproteinase-1 (MMP-1), collagenase-3 (MMP-13), stromelysin-1 (MMP-3), stromelysin-2 (MMP-10) and stromelysin-3 (MMP-11). These data demonstrate the clinical and biological relevance of the CXCL13-CXCR5 pathway and its role in PCa cell invasion and migration.

  16. Clinical significance of serum anti-annexin V antibodies in Egyptian patients with scleroderma.

    PubMed

    El Serougy, Iman M; Shahin, Amira A; Soliman, Doaa A; Akhnoukh, Amany F; Mousa, Somaia M

    2009-01-01

    The pathogenesis of scleroderma encompasses vascular, immunological, and fibrotic processes, which contribute to clinical manifestations. We investigated the prevalence of anti-annexin V IgG and IgM antibodies in sera of scleroderma patients and their relation to the presence of other antibodies and development of disease morbidity. Sera of 40 scleroderma patients and 15 healthy controls were examined for IgG and IgM anti-annexin V antibodies by ELISA and anticentromere antibodies by indirect immunofluorescence. Serum level of anti-annexin V IgG antibodies in scleroderma patients was significantly higher than that of the control (P < 0.001) and correlated significantly with the presence of digital ischemia (P = 0.023) and pulmonary fibrosis (P = 0.02). IgM isotype was comparable between patients and controls (P = 0.317). Anticentromere antibodies are more prevalent in the limited cutaneous subtype (P = 0.017). In conclusion, measurement of serum anti-annexin V IgG antibodies in scleroderma patients may be important for early diagnosis of vascular and pulmonary complications.

  17. Clinical significance of peripheral blood erythroblastosis after hematopoietic stem cell transplantation.

    PubMed

    Goyama, Susumu; Kanda, Yoshinobu; Nannya, Yasuhito; Ogawa, Seishi; Asano-Moki, Yuki; Ogawa, Natsu; Nakagawa, Masahiro; Sakata-Yanagimoto, Mamiko; Kawazu, Masahito; Komeno, Yukiko; Imai, Yoichi; Hangaishi, Akira; Kurokawa, Mineo; Tsujino, Shiho; Aoki, Katsunori; Chiba, Shigeru; Motokura, Toru; Hirai, Hisamaru

    2004-12-01

    Erythroblasts (EBL) are normally not observed in peripheral blood, but may be found in patients suffering from a variety of severe diseases. The detection of EBL in peripheral blood has been shown to be associated with a poor prognosis. However, the clinical significance of peripheral erythroblastosis after hematopoietic stem cell transplantation (HSCT) has not been evaluated. We retrospectively analyzed the records of 161 patients who underwent HSCT at our hospital from June 1995 to October 2001. EBL at any level were detected in 94% of the patients. Forty-four and 11 patients experienced erythroblastosis exceeding 200 and 1,000/ul, respectively. The erythroblast count was higher in patients who died than in the survivors (geometric mean value 184 vs. 100/ul, P=0.01). High-level erythroblastosis ( >1,000/ul) within 180 days after HSCT was associated with an extremely poor prognosis (median survival 22.5 days). Among the possible confounding factors, the use of total body irradiation (RR 2.35, 95% CI 1.22 - 4.54, P=0.011) and the disease status before transplantation (RR 2.51, 95% CI 1.15 - 5.49, P=0.021) were independent significant factors for erythroblastosis after HSCT. As for post-transplant events, a high EBL concentration was frequently preceded by graft-vs.-host disease, thrombotic microangiopathy, hypoxia, and hematological relapse.

  18. Clinical significance of vascular endothelial growth factor in hepatitis C related hepatocellular carcinoma in Egyptian patients

    PubMed Central

    Atta, Mohamed Magdi El-Sadek Ali; Atta, Hazem Mahmoud; Gad, Magdy Abdel-Mawgoud; Rashed, Laila Ahmad; Said, Ebada M; Hassanien, Sharaf El-Sayed Ali; Kaseb, Ahmed O

    2016-01-01

    Background and aims Several angiogenic factors are involved in the development and progression of hepatocellular carcinoma (HCC), a hypervascular tumor. Vascular endothelial growth factor (VEGF) is a primary driving force for angiogenesis, and its overexpression has been reported in HCC. However, the significance of plasma and tissue VEGF levels in HCC in Egyptian patients with chronic hepatitis C (CHC) infection is understudied. The aim of this study was to evaluate the role of VEGF (measured in plasma and liver tissue) in patients with hepatitis C virus-related HCC and to assess its significance in the diagnosis and prognosis of HCC. Materials and methods A total of 90 subjects were studied. Among 90 subjects, 60 with CHC were examined and were subdivided into two groups: 30 patients with CHC-related HCC (HCC group) and 30 patients with CHC without HCC (non-HCC group). Thirty apparently healthy subjects served as the control group. VEGF was estimated in plasma by enzyme-linked immunosorbent assay and its expression in liver tissue was evaluated by real-time polymerase chain reaction. VEGF expression level and its relationship to tumor parameters, patients’ liver function profile, and patients’ clinical parameters were also investigated. Results Plasma VEGF levels in the HCC group were significantly higher than those of the non-HCC group, and both groups had significantly higher plasma VEGF levels than did the control group. Liver tissue VEGF expression was significantly higher in the HCC group than in the non-HCC group and positively correlated with plasma VEGF in the HCC group. The plasma VEGF levels were positively correlated with patients’ age, aspartate aminotransferase levels, serum alpha-fetoprotein levels, the presence of portal vein thrombosis, and the number of hepatic focal lesions in the HCC group. However, plasma VEGF levels were not significantly correlated with the Child-Pugh score, alanine aminotransferase levels, the size of focal lesions

  19. The clinical significance of preoperative brain magnetic resonance imaging in pediatric cochlear implant recipients.

    PubMed

    Moon, Il Joon; Kim, Eun Yeon; Park, Ga-Young; Jang, Min Seok; Kim, Ji Hye; Lee, Jeehun; Chung, Won-Ho; Cho, Yang-Sun; Hong, Sung Hwa

    2012-01-01

    Although central nervous system abnormalities are incidentally detected in preoperative brain magnetic resonance imaging (MRI) studies in pediatric cochlear implant (CI) candidates, the clinical significance of the abnormalities remains unclear. We aimed to assess post-implantation auditory and speech performance in patients with brain lesions seen on MRI. Pediatric CI recipients (n = 177) who underwent preoperative MRI scans of the brain between January 2002 and June 2009 were included in this study. Patients with brain lesions on MRI were reviewed and categorized into the following groups: brain parenchymal lesions (focal vs. diffuse), ventriculomegaly, and extra-axial lesion. The main communication mode as well as progress in auditory perception and speech production were evaluated preoperatively and at 3, 6, 12, and 24 months postoperatively. Performance in patients with brain lesions was compared with the age- and sex-matched control group. Various brain lesions were found in 27 out of 177 patients. Children with brain lesions who received CIs showed gradual progress in auditory and speech outcomes for 2 years, though performance was reduced compared with the control group. In addition, there was a significant difference in the main communication mode between the two groups at 2 years following cochlear implantation. This difference was especially significant in patients with diffuse brain parenchymal lesions after further stratification of the brain lesion group. Preoperative brain MRI may have a role in improving the prediction of adverse outcomes in pediatric CI recipients. In particular, children with diffuse brain parenchymal lesions should be counseled regarding the poor prognosis preoperatively, and followed up with special attention.

  20. Clinical significance of antibody to hepatitis B core antigen in multitransfused hemodialysis patients

    PubMed Central

    Elghannam, Doaa M.; Aly, Rabab M.; Goda, Enas F.; Eltoraby, Ehab E.; Farag, Raghda E.

    2009-01-01

    Background: In spite of the progress made in the prevention of transfusion transmitted infections over the last few years, transmission of HBV infection through transfusion of HBsAg negative blood has been documented. Objectives: To assess the frequency and clinical significance of anti-HBc in multitransfused hemodialysis patients. Materials and Methods: One hundred and forty-three hemodialysis patients who had been receiving blood regularly with an average of 39.4 ± 7.579 months on hemodialysis were enrolled in this study. HBV markers (HBsAg, anti-HBc, anti-HBs) were measured in these patients and in 100 healthy controls by the ELISA technique. The following data were obtained for all patients: socio demographic data, number of blood transfusions and some laboratory investigations. Results: In our patients, anti-HBc was positive in 9%, anti HBs in 7%, coexistant HbsAg/anti-HBc in 2.8% and anti HBc/anti HBs in 18.9%, meanwhile no patients were positive for HBsAg alone. In patients with only positive anti-HBc, the levels of anti-HBc were significantly related to abnormal results of liver function. In patients with positive anti-HBs/anti-HBc (n = 27), 18 patients had abnormal liver function, and 9 patients had normal liver function with no significant difference between them. Conclusions: This study suggests that hepatitis B prevalence in our multitransfused hemodialysis patients is far in excess of that anticipated on the basis of HBsAg prevalence. Absence of HBsAg in the blood of hemodialyzed patients may not be sufficient to ensure lack of circulating HBV, and isolated positivity of anti-HBc may be a possible indicator of active hepatitis B infection. PMID:20041091

  1. Expression pattern and clinical significance of DNA methyltransferase 3B variants in gastric carcinoma.

    PubMed

    Su, Xianwei; Lv, Chengyu; Qiao, Fengchang; Qiu, Xuemei; Huang, Wenbin; Wu, Qingxiang; Zhao, Zhujiang; Fan, Hong

    2010-03-01

    The aim of this study was to detect the expression pattern of DNA methyltransferase 3B (DNMT3B) variants in primary gastric cancer (GC) and to explore the clinical significance of DNMT3B variants in gastric carcinogenesis. Specific polymerase chain reaction (PCR) primer sets were designed to distinguish individual DNMT3B variants according to their splicing patterns. Expression levels of DNMT3B variants were assessed by quantitative real-time RT-PCR in gastric cancer tissue, normal gastric mucosae and GC cell lines. The relationship between the expression patterns of the DNMT3B variants and corresponding clinical information was analyzed by observing the expression levels of different variants in the tumors. These results demonstrate that DNMT3B overexpression is related to late phase invasion (P=0.029) and intestinal type (P=0.012) in GC. DNMT3B3 expression was higher in normal tissue, compared to tumor tissue (P=0.033). In contrast, only 18, 32 and 35% of the patient tumors overexpressed DNMT3B1, DNMT3B4 and DNMT3B5, respectively. While taking into account environmental factors (H. pylori, Epstein-Barr virus infection), H. pylori infection elevated DNMT3B1 and DNMT3B3 variants in tumors, while increasing DNMT3B4 in both tumor and non-cancerous tissues. Our findings indicated that the expression of DNMT3B3 is the major splice variant in normal gastric mucosae and may be affected by H. pylori infection. Elevated DNMT3B variants may influence the progression of gastric cancer and may possibly be a powerful indicator for the disease.

  2. Identification of major rice allergen and their clinical significance in children

    PubMed Central

    Jeon, You Hoon; Oh, Se Jo; Yang, Hyeon Jong; Lee, Soo Young

    2011-01-01

    Purpose Recently, an increase in the number of patients sensitized to rice allergen with or without clinical symptoms has been reported. This study was designed to determine the major allergens in rice and their clinical significance. Methods Twenty-four children (15 boys and 9 girls; mean age, 16.3 months) with allergic disease, who were sensitized to rice antigen (by UniCAP) in the Pediatric Allergy Respiratory Center at Soonchunhyang University Hospital, were enrolled in this study. The allergenicity of various types of rice (raw, cooked, and heat-treated, simulated gastric fluid [SGF], and simulated intestinal fluid [SIF]) was investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoglobulin E (IgE) immunoblots. The patients' medical records, including laboratory data and allergy symptoms after ingestion of rice were reviewed. Results Patients were sensitized to an average of 13.5 food antigens and their mean total IgE was 6,888.7 kU/L. In SDS-PAGE, more than 16 protein bands were observed in the raw rice, whereas only 14-16 kDa and 31-35 kDa protein bands were observed in cooked rice. The common SDS-PAGE protein bands observed in SGF-, SIF-, and heat-treated rice were 9, 14, and 31 kDa. In a heated-rice IgE immunoblot, protein bands of 9, 14, and 31-33 kDa were found in 27.8%, 38.9%, and 38.9% of all sera, respectively, and in 50%, 50%, and 75%, of ser a from the 4 symptomatic patients, respectively. Conclusion The 9-, 14-, and 31-kDa protein bands appeared to be the major allergens responsible for rice allergy symptoms. PMID:22232624

  3. Clinical significance of antibodies against neutrophils in patients with inflammatory bowel disease and primary sclerosing cholangitis.

    PubMed Central

    Seibold, F; Weber, P; Klein, R; Berg, P A; Wiedmann, K H

    1992-01-01

    The presence of perinuclear antibodies against neutrophils (pANCA) has been detected recently in sera of patients with inflammatory bowel disease and primary sclerosing cholangitis. In order to evaluate their clinical significance, sera from 126 patients with inflammatory bowel disease (80 Crohn's disease and 46 ulcerative colitis and 22 patients with primary sclerosing cholangitis were examined for pANCA by indirect immunofluorescence on liver sections and cytocentrifuge slides of neutrophils and by immunoblot. Perinuclear antibodies against neutrophils were found in 83% of patients with ulcerative colitis in 88% of patients with primary sclerosing cholangitis and inflammatory bowel disease, in 40% of patients with primary sclerosing cholangitis but without inflammatory bowel disease, and in 25% of patients with Crohn's disease using the immunofluorescence test. Titres of pANCA ranged from 1:10 to 1:1000 in ulcerative colitis and primary sclerosing cholangitis (median 1:100), whereas in Crohn's disease only four patients had titres of more than 1:10. The occurrence of pANCA did not correlate with clinical activity of Crohn's disease and primary sclerosing cholangitis whereas in ulcerative colitis high titres of pANCA were found mainly in active disease. Using an immunoblot system with sonified neutrophils as antigen, 82% of sera from patients with primary sclerosing cholangitis reacted with up to five different determinants, whereas only 12% of sera from patients with Crohn's disease and 11% of sera with ulcerative colitis detected one of the determinants, suggesting different antigens involved in pANCA reaction. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:1612483

  4. Internight sleep variability: its clinical significance and responsiveness to treatment in primary and comorbid insomnia.

    PubMed

    Sánchez-Ortuño, María M; Edinger, Jack D

    2012-10-01

    Although sleep diary and actigraphy data are usually collected daily for 1 or 2 weeks, traditional analytical approaches aggregate these data into mean values. Internight variability of sleep often accompanies insomnia. However, few studies have explored the relevance of this 'construct' in the context of diagnosis, clinical impact, treatment effects and/or whether having 'variable sleep' carries any prognostic significance. We explored these questions by conducting secondary analyses of data from a randomized clinical trial. The sample included primary (PI: n = 40) and comorbid insomnia (CMI: n = 41) sufferers receiving four biweekly sessions of cognitive-behavioural therapy (CBT) or sleep hygiene education. Using the within-subject standard deviations of diary- and actigraphy-derived measures collected for 2-week periods [sleep onset latency (SOL), wake after sleep onset (WASO), total sleep time (TST) and sleep efficiency (SE)], we found that CMI sufferers displayed more variable self-reported SOLs and SEs than PI sufferers. However, higher variability in diary and actigraphy-derived measures was related to poorer sleep quality only within the PI group, as measured by the Pittsburgh Sleep Quality Index (PSQI). Within both groups, the variability of diary-derived measures was reduced after CBT, but the variability of actigraphy-derived measures remained unchanged. Interestingly, the variability of actigraphy measures at baseline was correlated with PSQI scores at 6-month follow-up. Higher SOL variability was associated with worse treatment outcomes within the PI group, whereas higher WASO variability was correlated with better treatment outcomes within the CMI group. Sleep variability differences across insomnia diagnoses, along with their distinctive correlates, suggest that mechanisms underlying the sleep disruption/complaint and treatment response in both patient groups are distinct. Further studies are warranted to support variability as a useful metric in

  5. Proteasome inhibition rescues clinically significant unstable variants of the mismatch repair protein Msh2

    PubMed Central

    Arlow, Tim; Scott, Kristan; Wagenseller, Aubrey; Gammie, Alison

    2013-01-01

    MSH2 is required for DNA mismatch repair recognition in eukaryotes. Deleterious mutations in human MSH2 account for approximately half of the alleles associated with a common hereditary cancer syndrome. Previously, we characterized clinically identified MSH2 missense mutations, using yeast as a model system, and found that the most common cause of defective DNA mismatch repair was low levels of the variant Msh2 proteins. Here, we show that increased protein turnover is responsible for the reduced cellular levels. Increasing gene dosage of more than half of the missense alleles fully restored function. A titration experiment revealed that raising the expression level of one variant to less than wild-type levels restored mismatch repair, suggesting that overexpression is not always required to regain function. We found that the ubiquitin-mediated proteasome degradation pathway is the major mechanism for increased turnover of the Msh2 variants and identified the primary ubiquitin ligase as San1. Deletion of San1 restored protein levels for all but one variant, but did not elevate wild-type Msh2 levels. The unstable variants interacted with San1, whereas wild-type Msh2 did not. Additionally, san1Δ suppressed the mismatch repair defect of unstable variants. Of medical significance, the clinically approved drug Bortezomib partially restored protein levels and mismatch repair function for low-level variants and reversed the resistance to cisplatin, a common chemotherapeutic. Our results provide the foundation for an innovative therapeutic regime for certain mismatch-repair-defective cancers that are refractory to conventional chemotherapies. PMID:23248292

  6. Clinical significance of the appearance of abnormal protein band in patients with multiple myeloma.

    PubMed

    Jo, Jae-Cheol; Yoon, Dok Hyun; Kim, Shin; Lee, Kyoungmin; Kang, Eun Hee; Jang, Seongsoo; Park, Chan-Jeoung; Chi, Hyun-Sook; Huh, Jooryung; Park, Chan-Sik; Suh, Cheolwon

    2014-03-01

    Multiple myeloma (MM) is characterized by clonal expansion of malignant bone marrow cells producing a unique monoclonal immunoglobulin. The appearance of abnormal protein band (APB) in MM has been reported during follow-up. We aimed to evaluate the clinical characteristics and outcomes of patients with APB in a single center cohort. A total of 377 consecutive MM patients were treated at the Asan Medical Center between January 2002 and December 2012. We compared clinical characteristics and survival outcome between those with and without APB. Of the 377 patients, 34 (9 %) experienced APB. They comprised 18.2 % (27/148) of patients treated with autologous stem cell transplantation (ASCT) and 3.1 % (7/229) of those not receiving ASCT. APB occurred after a median of 7.9 months (range, 2.2-95.7 months) from diagnosis. Immunoglobulin isotypes at diagnosis were as follows: IgG (n = 10), IgA (n = 8), IgD (n = 5), free κ (n = 4), and free λ (n = 7). Nine patients experienced a second APB. With a median follow-up of 54.1 months, the median overall survival (OS) has not been reached in patients with APB and was 38.3 months in patients without (P < 0.001). Multivariate analysis indicated that the development of APB was a significant favorable prognostic factor for OS (hazard ratio 0.21; 95 % confidence interval 0.08-0.52). Serum β₂-microglobulin, albumin, creatinine, and ASCT were also independent prognostic factors for OS. Further investigation is required to establish the mechanisms underlying APB in MM.

  7. [Monoclonal gammopathies of indetermined significance: diagnosis and clinical follow-up guidelines].

    PubMed

    Parreira, Joana; Lúcio, Paulo; João, Cristina; Macedo, Ana; Sarmento, Ana Bela; Geraldes, Catarina; Gonçalves, Cristina; Esteves, Graça

    2014-01-01

    The Portuguese group of multiple myeloma of the Portuguese Society of Hematology proposes a national protocol for diagnosis and clinical follow-up of monoclonal gammopathies. The proposed protocol aims to standardize clinical management of monoclonal gammopathies. Furthermore, it would also define the major risk factors for progression to Multiple Myeloma that require a precocious close articulation between general practitioners and a Hematology Clinic.

  8. Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions

    PubMed Central

    2016-01-01

    Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies suggest that DME, DR and AMD are inflammatory conditions characterized by a breakdown of the blood-retinal barrier, inflammatory processes and an increase in vascular permeability. Key factors that seem to have a dominant role in DME, DR and AMD are angiotensin II, prostaglandins and the vascular endothelial growth factor and a deficiency of anti-inflammatory bioactive lipids. The imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DME, DR and AMD. This implies that bioactive lipids that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DME, DR and AMD. PMID:27695506

  9. Diabetic macular edema, retinopathy and age-related macular degeneration as inflammatory conditions.

    PubMed

    Das, Undurti N

    2016-10-01

    Diabetic macular edema (DME) and diabetic retinopathy (DR) are complications affecting about 25% of all patients with long-standing type 1 and type 2 diabetes mellitus and are a major cause of significant decrease in vision and quality of life. Age-related macular degeneration (AMD) is not uncommon, and diabetes mellitus affects the incidence and progression of AMD through altering hemodynamics, increasing oxidative stress, accumulating advanced glycation end products, etc. Recent studies suggest that DME, DR and AMD are inflammatory conditions characterized by a breakdown of the blood-retinal barrier, inflammatory processes and an increase in vascular permeability. Key factors that seem to have a dominant role in DME, DR and AMD are angiotensin II, prostaglandins and the vascular endothelial growth factor and a deficiency of anti-inflammatory bioactive lipids. The imbalance between pro- and anti-inflammatory eicosanoids and enhanced production of pro-angiogenic factors may initiate the onset and progression of DME, DR and AMD. This implies that bioactive lipids that possess anti-inflammatory actions and suppress the production of angiogenic factors could be employed in the prevention and management of DME, DR and AMD.

  10. [Abnormality of blood coagulation indexes in patients with de novo acute leukemia and its clinical significance].

    PubMed

    Xiao, Fang-Fang; Hu, Kai-Xun; Guo, Mei; Qiao, Jian-Hui; Sun, Qi-Yun; Ai, Hui-Sheng; Yu, Chang-Lin

    2013-04-01

    To explore hemorrhage risk and the clinical significance of abnormal change of prothrombin time (PT), activated partial thromboplastin time (APTT), plasma fibrinogen (FIB), plasma thrombin time (TT) and d-dimer (D-D) in de novo acute leukemia (except for APL), the different bleeding manifestations of 114 cases of de novo acute leukemia with different coagulation indexes were analyzed retrospectively. The correlation between these blood coagulation indexes and the possible correlative clinical characteristics were analysed, including age, sex, type of acute leukemia, initial white blood cell(WBC) and platelet(Plt) count, the proportion of blast cells in bone marrow and cytogenetic abnormality of patients at diagnosis. The results indicated that the incidence of abnormal blood coagulation was as high as 78.1% for de novo AL patients. These patients with 5 normal blood coagulation indexes may have mild bleeding manifestation, but the more abnormal indexes, the more severe bleeding. Both PT and D-D were sensitive indexes for diagnosis of level II bleeding. Incidence of abnormal blood coagulation significantly correlates with the proportion of blast cells in bone marrow (χ(2) = 4.184, OR = 1.021, P < 0.05) and more with D-D (P < 0.01), while age, sex, type of AL, WBC count, Plt count and abnormality of cytogenetics did not correlate with abnormal blood coagulation. It is concluded that the coagulation and fibrinolysis are abnormal in most patients with de novo acute leukemia. More abnormal indexes indicate more severe bleeding, and both PT and D-D are sensitive indexes for diagnosis of level II bleeding. Higher proportion of blast cells in bone marrow predicts higher incidence of abnormal blood clotting. Acute leukemia with elderly age, high white blood cell count and adverse cytogenetics do not predict severer abnormal blood clotting. Detection of PT, APTT, TT, FIB, and D-D may help to judge whether the patients are in a state of hypercoagulability or disseminated

  11. [Possible mechanism of production of the musical second heart sound and its clinical significance].

    PubMed

    Fukuda, N; Hosoi, K; Iuchi, A; Ogawa, S; Kageji, Y; Hayashi, M; Yoshimoto, K; Tanimoto, M; Oki, T

    1991-01-01

    To investigate the predisposing factors and the clinical significance of the musical aortic component of the second heart sound (musical S2), 18 patients with musical S2 (musical group) among the consecutive 2,000 patients with phonocardiographic examination were noninvasively studied by analyzing underlying diseases, phonocardiographic findings, organic changes of the aortic valve, severity of aortic regurgitation and left ventricular dysfunction. Organic changes of the aortic valve were assessed by two-dimensional echocardiography, and aortic regurgitation was assessed by color Doppler flow imaging. Twenty-two normal subjects (normal group) and 17 patients with essential hypertension (hypertensive group) served as controls. Mean ages were matched among the three groups. 1. Left ventricular dilatation (seven patients) and hypertension (six patients) were the dominant part of underlying disease in the musical group. 2. Musical S2 was classified in the following two types based on the phonocardiographic characteristics; musical vibrations followed immediately after the accentuated S2, and the S2 which was replaced by regular vibratory waves. 3. Frequency of the musical vibrations ranged from 120 to 200 Hz, and its duration ranged from 60 to 120 msec. Amplitude of the musical vibrations decreased by inhalation of amyl nitrite, but increased by infusion of methoxamine. In a case with mild rheumatic valve disease, methoxamine induced marked intensification of the amplitude and prolongation of the duration of the musical vibrations, finally giving a typical cooing murmur. 4. Echo intensity of the aortic valve tended to be higher in the musical group than in the other two groups. 5. Echocardiographically, aortic regurgitation appeared more frequently in the musical group (88%) than in the normal (36%) and hypertensive (41%) groups. Area of the aortic regurgitant signal was significantly larger in the musical group (4.1 +/- 1.4 cm2) than in the normal (1.2 +/- 0.8 cm2

  12. Clinical significance of para-aortic lymph node dissection and prognosis in ovarian cancer.

    PubMed

    Li, Xianxian; Xing, Hui; Li, Lin; Huang, Yanli; Zhou, Min; Liu, Qiong; Qin, Xiaomin; He, Min

    2014-03-01

    Lymph node metastasis has an important effect on prognosis of patients with ovarian cancer. Moreover, the impact of para-aortic lymph node (PAN) removal on patient prognosis is still unclear. In this study, 80 patients were divided into groups A and B. Group A consisted of 30 patients who underwent PAN + pelvic lymph node (PLN) dissection, whereas group B consisted of 50 patients who only underwent PLN dissection. Analysis of the correlation between PAN clearance and prognosis in epithelial ovarian cancer was conducted. Nineteen cases of lymph node metastasis were found in group A, among whom seven cases were positive for PAN, three cases for PLN, and nine cases for both PAN and PLN. In group B, 13 cases were positive for lymph node metastasis. Our study suggested that the metastatic rate of lymph node is 40.0%. Lymph node metastasis was significantly correlated with FIGO stage, tumor differentiation, and histological type both in groups A and B (P < 0.05). In groups A and B, the three-year survival rates were 77.9% and 69.0%, and the five-year survival rates were 46.7% and 39.2%, respectively. However, the difference was not statistically significant (P > 0.05). The three-year survival rates of PLN metastasis in groups A and B were 68.5% and 41.4%, and the five-year survival rates were 49.7% and 26.4%, respectively. Furthermore, PLN-positive patients who cleared PAN had significantly higher survival rate (P = 0.044). In group A, the three-year survival rates of positive and negative lymph nodes were 43.5% and 72.7%, and the five-year survival rates were 27.2% and 58.5%, respectively. The difference was statistically significant (P = 0.048). Cox model analysis of single factor suggested that lymph node status affected the survival rate (P < 0.01), which was the death risk factor. Consequently, in ovarian carcinoma cytoreductive surgery, resection of the para-aortic lymph node, which has an important function in clinical treatment and prognosis of patients with

  13. Radiation-induced bystander effect in healthy G(o) human lymphocytes: biological and clinical significance.

    PubMed

    Belloni, Paola; Latini, Paolo; Palitti, Fabrizio

    2011-08-01

    To study the bystander effects, G(0) human peripheral blood lymphocytes were X-irradiated with 0.1, 0.5 and 3 Gy. After 24h, cell-free conditioned media from irradiated cultures were transferred to unexposed lymphocytes. Following 48 h of medium transfer, viability, induction of apoptosis, telomere shortening, reactive oxygen species (ROS) levels and micronuclei (after stimulation) were analyzed. A statistically significant decrement in cell viability, concomitant with the loss of mitochondrial membrane potential, telomere shortening, increases in hydrogen peroxide (H(2)O(2)) and superoxide anion (O(2)(-)) with depletion of intracellular glutathione (GSH) level, and higher frequencies of micronuclei, were observed in bystander lymphocytes incubated with medium from 0.5 and 3 Gy irradiated samples, compared to lymphocytes unexposed. Furthermore, no statistically significant difference between the response to 0.5 and 3 Gy of irradiation in bystander lymphocytes, was found. However, when lymphocytes were irradiated with 0.1 Gy, no bystander effect with regard to viability, apoptosis, telomere length, and micronuclei was observed, although a high production of ROS level persisted. Radiation in the presence of the radical scavenger dimethyl sulfoxide (DMSO) suppressed oxidative stress induced by 3 Gy of X-rays with the effective elimination of bystander effects, suggesting a correlation between ROS and bystander signal formation in irradiated cells. The data propose that bystander effect might be mostly due to the reactions of radiation induced free radicals on DNA, with the existence of a threshold at which the bystander signal is not operative (0.1 Gy dose of X-rays). Our results may have clinical implications for health risk associated with radiation exposure.

  14. Clinical significance of the muscle-retracting sign during colorectal endoscopic submucosal dissection

    PubMed Central

    Toyonaga, Takashi; Tanaka, Shinwa; Man-I, Mariko; East, James; Ono, Wataru; Nishino, Eisei; Ishida, Tsukasa; Hoshi, Namiko; Morita, Yoshinori; Azuma, Takeshi

    2015-01-01

    Background and study aims: During colorectal endoscopic submucosal dissection (ESD), the feature of a muscle layer being pulled toward a neoplastic tumor is sometimes detected. We call this feature the muscle-retracting sign (MR sign). The aim of this study was to evaluate whether the MR sign is associated with particular types of neoplastic lesions and whether it has any clinical significance for ESD sessions. Patients and methods: A total of 329 patients underwent ESD for 357 colorectal neoplasms. The frequency of positivity for the MR sign was evaluated in different morphologic and histopathologic types of neoplasm. The success rate of complete resection and the incidence of complications were also evaluated according to whether lesions were positive or negative for the MR sign. Results: The rates of positivity for the MR sign in the various lesion types were as follows: laterally spreading tumor – granular nodular mixed type (LST-G-M), 9.6 %; laterally spreading tumor – granular homogeneous type (LST-G-H) and laterally spreading tumor – nongranular type (LST-NG), 0 %; sessile type, 41.2 %. The resection rate was 100 % (329 /329) in lesions negative for the MR sign; however, it was 64.3 % (18 /28) in lesions positive for the MR sign, which was significantly lower (P < 0.001). Conclusions: The MR sign was present only in some protruding lesions, and more importantly, it was associated with a high risk of incomplete tumor removal by ESD. Our data indicate that lesions positive for the MR sign lesions should be dissected with great caution; alternatively, based on the features of the individual case, a switch to surgery should be considered for the benefit of the patient. PMID:26171438

  15. Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

    PubMed Central

    Pistelli, Mirco; Caramanti, Miriam; Biscotti, Tommasina; Santinelli, Alfredo; Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano

    2014-01-01

    Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target. PMID:24978437

  16. Expression and clinical significance of erb-B receptor family in hepatocellular carcinoma

    PubMed Central

    Ito, Y; Takeda, T; Sakon, M; Tsujimoto, M; Higashiyama, S; Noda, K; Miyoshi, E; Monden, M; Matsuura, N

    2001-01-01

    In order to elucidate the clinical significance of the erbB family, epidermal growth factor receptor (EGF-R), c-erbB-2, c-erbB-3 and c-erbB-4 in hepatocellular carcinoma (HCC), we investigated the expression of these proteins by means of immunohistochemistry for HCC as well as adjacent noncancerous lesions. EGF-R was expressed in 68% of the HCC examined and showed correlation with the proliferating activity, stage, intrahepatic metastasis and carcinoma differentiation. c-erbB-2 was expressed in only 21% of the cases and showed no relationships with the clinicopathological parameters. c-erbB-3 protein was observed in 84% of the HCC and 38.1% of the noncancerous lesions. Its expression in HCC was equal to or greater than noncancerous lesions in 90.5% of the cases, and was related to the stage, portal invasion, cell proliferating activity, tumour size, intrahepatic metastasis and carcinoma differentiation. c-erbB-4 protein was expressed in 61.0% of HCC and in as much as 86.1% of the noncancerous lesions. Unlike the expression of c-erbB-3, that of c-erbB-4 in HCC was less than that of the adjacent noncancerous lesions in 51.2% of the cases. No statistical significance could be established between this protein expression in HCC and clinicopathological features. EGF-R and c-erbB-3 affected disease-free survival, but were not recognized as independent prognostic factors by multivariate analysis. The present study suggests that, of the four receptors, EGF-R and c-erbB-3 play important roles in the progression of HCC. © 2001 Cancer Research Campaign www.bjcancer.com PMID:11355950

  17. Look what else we found - clinically significant abnormalities detected during routine ROP screening

    PubMed Central

    Jayadev, Chaitra; Vinekar, Anand; Bauer, Noel; Mangalesh, Shwetha; Mahendradas, Padmamalini; Kemmanu, Vasudha; Mallipatna, Ashwin; Shetty, Bhujang

    2015-01-01

    Purpose: The purpose of this study was to report the spectrum of anterior and posterior segment diagnoses in Asian Indian premature infants detected serendipitously during routine retinopathy of prematurity (ROP) screening during a 1 year period. Methods: A retrospective review of all Retcam (Clarity MSI, USA) imaging sessions during the year 2011 performed on infants born either <2001 g at birth and/or <34.1 weeks of gestation recruited for ROP screening was performed. All infants had a minimum of seven images at each session, which included the dilated anterior segment, disc, and macula center and the four quadrants using the 130° lens. Results: Of the 8954 imaging sessions of 1450 new infants recruited in 2011, there were 111 (7.66%) with a diagnosis other than ROP. Anterior segment diagnoses seen in 31 (27.9%) cases included clinically significant cataract, lid abnormalities, anophthalmos, microphthalmos, and corneal diseases. Posterior segment diagnoses in 80 (72.1%) cases included retinal hemorrhages, cherry red spots, and neonatal uveitis of infective etiologies. Of the 111 cases, 15 (13.5%) underwent surgical procedures and 24 (21.6%) underwent medical procedures; importantly, two eyes with retinoblastoma were detected which were managed timely. Conclusions: This study emphasizes the importance of ocular digital imaging in premature infants. Visually significant, potentially life-threatening, and even treatable conditions were detected serendipitously during routine ROP screening that may be missed or detected late otherwise. This pilot data may be used to advocate for a possible universal infant eye screening program using digital imaging. PMID:26139795

  18. Expression of RUNX3 gene in pancreatic adenocarcinoma and its clinical significance.

    PubMed

    Xue, L-N; Bai, F H; Wang, X-Y; Lin, M; Tan, Y; Yao, X-Y; Xu, K-Q

    2014-05-23

    We investigated the clinical significance of RUNX3 gene expression in human pancreatic carcinoma. Five samples of pancreatic tissues and 30 samples of pancreatic cancer tissues and paracancerous tissues were collected. RUNX3 expression was detected by real-time PCR and immunohistochemistry. The relationships between clinicopathological findings and the expression of RUNX3 were analyzed. The relative quantification level of RUNX3 mRNA expression in human pancreatic carcinoma tissues and paracancerous tissues was 2.60 (0.42-12.82) and 1.02 (0.19-3.58), respectively (P < 0.05). The percentage of positive cells expressing RUNX3 protein in human pancreatic tissues and paracancerous tissues was 45.5 ± 26.2 and 6.9 ± 6.0%, respectively (P < 0.01). The high RUNX3 group (N = 9) with 45.5% or more of the cancer cells staining for RUNX3 and the low RUNX3 group (N = 21) with less than 45.5% cancer cells staining for RUNX3. Low expression of RUNX3 correlated significantly with an advanced TNM stage (χ(2) = 6.897, P = 0.045), lymph node metastasis (χ(2) = 4.739, P = 0.029) and neural invasion (χ(2) = 5.44, P = 0.020). On the other hand, no association could be found between RUNX3 expression and clinicopathological variables including age, gender, tumor location, tumor size, tumor differentiation or the serum concentration of CEA and CA199. The expression of RUNX3 in pancreatic cancer tissues was obviously higher than that in the paracancerous tissues. Low expression of RUNX3 may have an important role in aggressiveness, lymph node metastasis and neural invasion in pancreatic cancer. In pancreatic carcinoma tissues, low expression of RUNX3 may indicate a poor prognosis.

  19. Locations and Clinical Significance of Non-Hemorrhagic Brain Lesions in Diffuse Axonal Injuries

    PubMed Central

    Chung, Sang Won; Nam, Taek Kyun; Kwon, Jeong Taik; Min, Byung Kook; Hwang, Sung Nam

    2012-01-01

    Objective Detection of focal non-hemorrhagic lesion (NHL) has become more efficient in diffuse axonal injury (DAI) patients using an MRI. The aims of this study are to find out the radiological distribution, progress of NHL and its clinical significance. Methods Between September 2005 and October 2011, 32 individuals with NHLs on brain MRI were enrolled. NHLs were classified by brain location into 4 major districts and 13 detailed locations including cortical and subcortical, corpus callosum, deep nuclei and adjacent area, and brainstem. The severity of NHL was scored from grades 1 to 4, according to the number of districts involved. Fourteen patients with NHL were available for MRI follow-up and an investigation of the changes was conducted. Results Thirty-two patients had 59 NHLs. The most common district of NHL was cortical and subcortical area; 15 patients had 20 NHSs. However the most common specific location was the splenium of the corpus callosum; 14 patients had 14 lesions. The more lesions patients had, the lower the GCS, however, this was not a statistically meaningful difference. On follow-up MRI in 14 patients, out of 24 lesions, 13 NHLs resolved, 5 showed cystic change, and 6 showed atrophic changes. Conclusion NHLs were located most commonly in the splenium and occur frequently in the thalamus and the mesial temporal lobe. Because most NHS occur concomitantly with hemorrhagic lesions, it was difficult to determine their effects on prognosis. Since most NHLs resolve completely, they are probably less significant to prognosis than hemorrhagic lesions. PMID:23133728

  20. Compression Angle of Ossification of the Posterior Longitudinal Ligament and Its Clinical Significance in Cervical Myelopathy

    PubMed Central

    Lee, Nam; Yoon, Do Heum; Kim, Keung Nyun; Shin, Hyun Chul; Shin, Dong Ah

    2016-01-01

    Objectives The correction of clinical and radiologic abnormalities in patients with symptomatic ossification of the posterior longitudinal ligament (OPLL) is the current mainstay of treatment. This study aimed to identify radiographic predictors of severity of myelopathy in patients with symptomatic OPLL. Methods Fifty patients with symptomatic cervical OPLL were enrolled. Based on Japanese Orthopedic Association (JOA) scores, patients were divided into either the mild myelopathy (n=31) or severe myelopathy (n=19) group. All subjects underwent preoperative plain cervical roentgenogram, computed tomography (CT), and MR imaging (MRI). Radiological parameters (C2–7 sagittal vertical axis, SVA; C2–7 Cobb angle; C2–7 range of motion, ROM; OPLL occupying ratio; and compression angle) were compared. Compression angle of OPLL was defined as the angle between the cranial and caudal surfaces of OPLL at the maximum level of cord compression Results The occupying ratio of the spinal canal, C2–7 Cobb angle, C2–7 SVA, types of OPLL, and C2–7 ROM of the cervical spine were not statistically different between the two groups. However, the OPLL compression angle was significantly greater (p=0.003) in the severe myelopathy group than in the mild myelopathy group and was inversely correlated with JOA score (r=-0.533, p<0.01). Furthermore, multivariate regression analysis demonstrated that the compression angle (B=-0.069, p<0.001) was significantly associated with JOA scores (R=0.647, p<0.005). Conclusion Higher compression angles of OPLL have deleterious effects on the spinal cord and decrease preoperative JOA scores. PMID:27651865

  1. Incidence, Prevalence, and Clinical Significance of Abnormal Hematologic Indices in Compensated Cirrhosis

    PubMed Central

    Qamar, Amir A.; Grace, Norman D.; Groszmann, Roberto J.; Garcia–Tsao, Guadalupe; Bosch, Jaime; Burroughs, Andrew K.; Ripoll, Cristina; Maurer, Rie; Planas, Ramon; Escorsell, Angels; Garcia–Pagan, Juan Carlos; Patch, David; Matloff, Daniel S.; Makuch, Robert; Rendon, Gabriel

    2011-01-01

    Background & Aims Patients with cirrhosis develop abnormal hematologic indices (HI) from multiple factors, including hypersplenism. We aimed to analyze the sequence of events and determine whether abnormal HI has prognostic significance. Methods We analyzed a database of 213 subjects with compensated cirrhosis without esophageal varices. Subjects were followed for approximately 9 years until the development of varices or variceal bleeding or completion of the study; 84 subjects developed varices. Abnormal HI was defined as anemia at baseline (hemoglobin, ≤13.5 g/dL for men and 11.5 g/dL for women), leukopenia (white blood cell counts, ≤4000/mm3), or thrombocytopenia (platelet counts, ≤150,000/mm3). The primary end points were death or transplant surgery. Results Most subjects had thrombocytopenia at baseline. Kaplan–Meier analysis showed that leukopenia occurred by 30 months (95% confidence interval, 18.5–53.6), and anemia occurred by 39.6 months (95% confidence interval, 24.1–49.9). Baseline thrombocytopenia (P = .0191) and leukopenia (P = .0383) were predictors of death or transplant, after adjusting for baseline hepatic venous pressure gradient (HVPG), and Child–Pugh scores. After a median of 5 years, a significant difference in death or transplant, mortality, and clinical decompensation was observed in patients who had leukopenia combined with thrombocytopenia at baseline compared with patients with normal HI (P < .0001). HVPG correlated with hemoglobin and white blood cell count (hemoglobin, r = −0.35, P < .0001; white blood cell count, r = −0.31, P < .0001). Conclusions Thrombocytopenia is the most common and first abnormal HI to occur in patients with cirrhosis, followed by leukopenia and anemia. A combination of leukopenia and thrombocytopenia at baseline predicted increased morbidity and mortality. PMID:19281860

  2. Calcareous concretions and psammoma bodies in sputum smears: do these similar structures have different clinical significance?

    PubMed

    Martínez-Girón, Rafael; Martínez-Torre, Santiago; Tamargo-Peláez, María Luisa; López-Cabanilles, María Dolores; Torre-Bayón, Concepción

    2014-09-01

    Different noncellular elements, such as round concentric calcified laminated structures, may be found in sputum smears. If these structures appear isolated on the background of the smear, the term usually used to describe them is "calcareous concretions" (CC). On the contrary, when the structures are part of epithelial cell groups or small tissue fragments, the term used to describe them is "Psammoma bodies" (PB). The aim of this work is to establish the relationship between these structures and pulmonary disease, especially lung carcinoma, by searching for the presence of CC and/or PB in sputum smears. Our study has taken as a basis 16.716 sputum smears from 696 patients obtained during a 7-year period (2003-2009). After reviewing them, it was found that from the total, 66 cases (0.39%) contained round calcified structures, 57 of them (0.34%) corresponding to CC, and the remaining 9 ones (0.05%) corresponding to PB. From these 57 CC cases, 56 corresponded to benign entities, and only one was found with lung carcinoma. On the other hand, from the 9 PB cases all of them (100%) were related to lung adenocarcinoma. We conclude that, even having a similar morphological structure, these aforementioned calcified structures we have observed in sputum smears have different and relevant clinical significance.

  3. Clinical significance of leukocyte-associated immunoglobulin-like receptor-1 expression in human cervical cancer

    PubMed Central

    Wang, Yue; Zhang, Xueshan; Miao, Fang; Cao, Yanning; Xue, Jiangnan; Cao, Qizhi; Zhang, Xiaoshu

    2016-01-01

    Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is broadly expressed on the majority of immune cells; however, the biological role of LAIR in solid tumors has yet to be elucidated. In the present study, using immunohistochemical staining analysis, the expression of LAIR-1 in human cervical cancer (HCC) and nontumor-adjacent tissue specimens was determined, and the results indicated that the expression of LAIR-1 in HCC tissue was higher compared with that in noncancerous tissue. The χ2 test was used to analyze the correlation between the expression of LAIR-1 in tumor tissues with clinicopathological parameters. The results showed that the expression of LAIR-1 in the cancer cell nucleus was significantly associated with tumor size, pathological differentiation, T classification and clinical stage. In addition, the expression in the cytoplasm was evidently associated with the number of positive lymph nodes. The HCC cell line, ME-180, which does not express LAIR-1, was stably transfected using LAIR-1 cDNA. Cell Counting Kit-8 and an annexin V assay showed that the overexpression of LAIR-1 in ME-180 cells suppressed the proliferation and anti-apoptosis capacity of the cells. These findings demonstrated that LAIR-1 is markedly overexpressed in HCC tissue, and that its expression status is associated with tumor progression. LAIR-1 may be a biomarker and target in the diagnosis and treatment of patients with HCC. PMID:28105100

  4. The Vital Capacity Is Vital: Epidemiology and Clinical Significance of the Restrictive Spirometry Pattern.

    PubMed

    Godfrey, Mark S; Jankowich, Matthew D

    2016-01-01

    Epidemiologic research has revealed a substantial portion of the general population with abnormal spirometry results that are characterized by decreased FEV1 and FVC but a preserved FEV1/FVC ratio. This restrictive spirometry pattern (RSP) is inconsistently defined in the literature and not well addressed by current guidelines; there is an accumulating body of evidence, however, that RSP is prevalent to a similar degree as airflow obstruction. Genetic and other risk factors for RSP, such as inhalational injuries and early life exposures, continue to be actively described. Although it seems that RSP is closely associated with the metabolic syndrome, diabetes, and systemic inflammation, it is not a simple marker of obesity. RSP is associated with adverse cardiovascular outcomes, as well as mortality, and it may be an underappreciated cause of functional impairments and respiratory symptoms. Improvement in outcomes in this population will require that clinicians have an appreciation for the significance of this spirometry pattern; additional research into the clinical and radiologic phenotype of these subjects is also needed. This article provides an overview of the recent developments in our understanding of this prevalent and highly morbid spirometry pattern.

  5. Clinical significance and prognostic value of Vav1 expression in Non-small cell lung cancer

    PubMed Central

    Qi, Yao; Kong, Fan-Ming; Deng, Qi; Li, Jing-Yi; Cui, Rui; Pu, Ye-Di; Zhai, Qiong-Li; Jia, Ying-Jie; Li, Yu-Ming

    2015-01-01

    Vav1 has been reported to be involved in human cancers, however, the expression and clinical significance of Vav1 in NSCLC are not fully understood. In the present study, we examined the expression of Vav1 in 170 NSCLC patients who underwent radical resection by the immunohistochemical analyses. The association between the Vav1 expression and clinicopathological variables was analyzed. The multivariate Cox proportional hazards model was conducted to determine the prognostic value of Vav1 on the long-term survival. The results showed that the elevated Vav1 expression was correlated positively with lymph node metastasis (P<0.001), T stage (P<0.001) and poor histological differentiation (P<0.001). Patients with negative or low Vav1 expression had better prognoses than those with high Vav1 expression (P<0.001). Multivariate analysis indicated that Vav1 was independent prognostic factor for overall survival (OS) (HR 2.079, 95% CI 1.564 to 2.762, P<0.001) and disease-free survival (DFS) (HR 1.810, 95% CI 1.391 to 2.356, P<0.001). Our findings showed that overexpressed Vav1 was correlated with aggressive tumor behavior. Val1 was an independent factor for NSCLC prognosis, which may serve as a novel prognostic factor and potential target to improve the long-term outcome of NSCLC. PMID:26396925

  6. Lymph node, peritoneal and bone marrow micrometastases in gastric cancer: Their clinical significance.

    PubMed

    Griniatsos, John; Michail, Othon; Dimitriou, Nikoletta; Karavokyros, Ioannis

    2012-02-15

    The 7th TNM classification clearly states that micrometastases detected by morphological techniques (HE stain and immunohistochemistry) should always be reported and calculated in the staging of the disease (pN1mi or M1), while patients in whom micrometastases are detected by non-morphological techniques (e.g., flow cytometry, reverse-transcriptase polymerase chain reaction) should still be classified as N0 or M0. In gastric cancer patients, micrometastases have been detected in lymph nodes, the peritoneal cavity and bone marrow. However, the clinical implications and/or their prognostic significance are still a matter of debate. Current literature suggests that lymph node micrometastases should be encountered for the loco-regional staging of the disease, while skip lymph node micrometastases should also be encountered in the total number of infiltrated lymph nodes. Peritoneal fluid cytology examination should be obligatorily performed in pT3 or pT4 tumors. A positive cytology classifies gastric cancer patients as stage IV. Although a curative resection is not precluded, these patients face an overall dismal prognosis. Whether patients with a positive cytology should be treated similarly to patients with macroscopic peritoneal recurrence should be evaluated further. Gastric cancer cells are detected with high incidence in the bone marrow. However, the published results make comparison of data between groups almost impossible due to severe methodological problems. If these methodological problems are overcome in the future, specific target therapies may be designed for specific groups of patients.

  7. Lymph node, peritoneal and bone marrow micrometastases in gastric cancer: Their clinical significance

    PubMed Central

    Griniatsos, John; Michail, Othon; Dimitriou, Nikoletta; Karavokyros, Ioannis

    2012-01-01

    The 7th TNM classification clearly states that micrometastases detected by morphological techniques (HE stain and immunohistochemistry) should always be reported and calculated in the staging of the disease (pN1mi or M1), while patients in whom micrometastases are detected by non-morphological techniques (e.g., flow cytometry, reverse-transcriptase polymerase chain reaction) should still be classified as N0 or M0. In gastric cancer patients, micrometastases have been detected in lymph nodes, the peritoneal cavity and bone marrow. However, the clinical implications and/or their prognostic significance are still a matter of debate. Current literature suggests that lymph node micrometastases should be encountered for the loco-regional staging of the disease, while skip lymph node micrometastases should also be encountered in the total number of infiltrated lymph nodes. Peritoneal fluid cytology examination should be obligatorily performed in pT3 or pT4 tumors. A positive cytology classifies gastric cancer patients as stage IV. Although a curative resection is not precluded, these patients face an overall dismal prognosis. Whether patients with a positive cytology should be treated similarly to patients with macroscopic peritoneal recurrence should be evaluated further. Gastric cancer cells are detected with high incidence in the bone marrow. However, the published results make comparison of data between groups almost impossible due to severe methodological problems. If these methodological problems are overcome in the future, specific target therapies may be designed for specific groups of patients. PMID:22403737

  8. The clinical significance of the gut microbiota in cystic fibrosis and the potential for dietary therapies.

    PubMed

    Li, Li; Somerset, Shawn

    2014-08-01

    Cystic fibrosis (CF) is characterised by many comorbidities related to aberrant mucosa and chronic inflammation in the respiratory and digestive systems. The intestinal mucosa serves as the primary interface between the gut microbiota and endocrine, neural and immune systems. There is emerging evidence that aberrant intestinal mucosa in CF may associate with an altered gut microbiota. Compared to healthy subjects, the overall bacterial abundance and species richness seems to be reduced in CF, accompanied by a trend in suppression of Firmicutes and Bacteroidetes spp. and an augmentation of potentially pathogenic species. There is also some concordance of gut and respiratory microbiotas in CF infants over time. The clinical significance of these observations awaits investigation. The gut microbiota have some potential in CF management by affecting inflammatory and immune responses, and influencing aberrant mucosa. As an important modifiable factor, diet therapies such as probiotics and prebiotics have shown initial promise in improving CF related conditions associated with chronic inflammation. More studies are needed to confirm this, as well as the efficacy of other dietary strategies such as modulating dietary fat and indigestible carbohydrate. Similarly, dietary modification of gut microbiota to optimise nutritional status in CF may be feasible, although more CF-specific studies are warranted.

  9. The prevalence and clinical significance of intestinal parasites in HIV-infected patients in Denmark.

    PubMed

    Stensvold, Christen Rune; Nielsen, Susanne Dam; Badsberg, Jens-Henrik; Engberg, Jørgen; Friis-Møller, Nina; Nielsen, Sanne Søgaard; Nielsen, Henrik Vedel; Friis-Møller, Alice

    2011-02-01

    To investigate the prevalence and clinical significance of intestinal parasites in human immunodeficiency virus (HIV)-infected patients, faecal specimens from 96 HIV-infected patients were submitted to microbiological analyses, including microscopy and polymerase chain reaction for protozoa and enteropathogenic bacteria. Results of microbiological analyses were compared with self-reported gastrointestinal complaints collected using a validated questionnaire. Thirty-two (33%) patients were positive for parasites. However, opportunistic parasites (Isospora and Cryptosporidium) were detected in only 2 instances. Entamoeba dispar was detected in 10 cases, 9 of which represented men who have sex with men (MSM). Despite generally low HIV RNA loads and high CD4+ T-cell counts, 42% of the 76 patients reporting symptoms complained of diarrhoea, 31% of whom were parasite-positive. The presence of diarrhoea was not associated with the presence or absence of parasites; neither was it associated with receiving highly active anti-retroviral therapy (HAART) in general, or protease inhibitors (PI) in particular. A CD4+ T-cell count <200 cells/mm³ was not associated with parasitic infection or with diarrhoea. The data show that diarrhoea is a common symptom among HIV-infected patients in Denmark, but do not indicate that the diarrhoea is due to intestinal parasites.

  10. Blastocystis: unravelling potential risk factors and clinical significance of a common but neglected parasite.

    PubMed

    Stensvold, C R; Lewis, H C; Hammerum, A M; Porsbo, L J; Nielsen, S S; Olsen, K E P; Arendrup, M C; Nielsen, H V; Mølbak, K

    2009-11-01

    Two independent studies were conducted to describe symptoms and potential risk factors associated with Blastocystis infection. Isolates were subtyped by molecular analysis. In the NORMAT study (126 individuals randomly sampled from the general population) 24 (19%) were positive for Blastocystis. Blastocystis was associated with irritable bowel syndrome (P=0.04), contact with pigs (P<0.01) and poultry (P=0.03). In the Follow-up (FU) study (follow-up of 92 Blastocystis-positive patients), reports on bloating were associated with subtype (ST) 2 (P<0.01), and blood in stool to mixed subtype infection (P=0.06). ST1 was more common in FU individuals (32%) than in NORMAT individuals (8%), whereas single subtype infections due to ST3 or ST4 were seen in 63% of the NORMAT cases and 28% of the FU cases. Only FU individuals hosted ST7, and ST6/7 infections due to ST7 or ST9 were characterized by multiple intestinal symptoms. The data indicate subtype-dependent differences in the clinical significance of Blastocystis.

  11. DNA methylation Profiles in Primary Cutaneous Melanomas are Associated with Clinically Significant Pathologic Features

    PubMed Central

    Thomas, Nancy E.; Slater, Nathaniel A.; Edmiston, Sharon N.; Zhou, Xin; Kuan, Pei-Fen; Groben, Pamela A.; Carson, Craig C.; Hao, Honglin; Parrish, Eloise; Moschos, Stergios J.; Berwick, Marianne; Ollila, David W.; Conway, Kathleen

    2014-01-01

    Summary DNA methylation studies have elucidated a methylation signature distinguishing primary melanomas from benign nevi and provided new insights about genes that may be important in melanoma development. However, it is unclear whether methylation differences among primary melanomas are related to tumor pathologic features with known clinical significance. We utilized the Illumina Golden Gate Cancer Panel array to investigate the methylation profiles of 47 primary cutaneous melanomas. Array-wide methylation patterns revealed a positive association of methylation with Breslow thickness and mutated BRAF, a negative association with mitotic rate, and a weak association with ulceration. Hierarchical clustering on CpG sites exhibiting the most variable methylation (n=235) divided the melanoma samples into three clusters, including a highly-methylated cluster that was positively associated with Breslow thickness and an intermediately-methylated cluster associated with Breslow thickness and mitotic rate. Our findings provide support for the existence of methylation-defined subsets in melanomas, with increased methylation associated with Breslow thickness. PMID:24986547

  12. Clinical and biological significance of glucocorticoid receptor (GR) expression in breast cancer.

    PubMed

    Abduljabbar, Rezvan; Negm, Ola H; Lai, Chun-Fui; Jerjees, Dena A; Al-Kaabi, Methaq; Hamed, Mohamed R; Tighe, Patrick J; Buluwela, Lakjaya; Mukherjee, Abhik; Green, Andrew R; Ali, Simak; Rakha, Emad A; Ellis, Ian O

    2015-04-01

    The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily of transcription factors, which exerts anti-proliferative and anti-apoptotic activities. The GR is expressed in a large proportion of breast cancer (BC) although levels generally decrease during cancer progression. This study aimed to determine the clinical and biological significance of GR expression using a large series of early-stage BC with long-term follow-up and BC cell lines. Immunohistochemistry was used to assess the expression of GR in 999 cases of primary invasive BC prepared as tissue microarrays. Reverse phase protein microarray was used to assess the expression of GR in MCF7 and MDA-MB-231 cell lines. Nuclear expression of GR was observed in 61.6 % of breast tumours and was associated with features of good prognosis including smaller tumour size and lower grade with less pleomorphism and low mitotic count. GR expression was positively correlated with expression of oestrogen (ER) and progesterone receptors. In ER-positive tumours, GR was associated with other features of favourable outcome including FOXA1, GATA3 and BEX1 expression, while low GR expression was associated with high Ki67, p53 and CD71 expression. GR expression is associated with features of good outcome but does not provide prognostic information independent of size, stage and grade. Understanding the receptor and its effects on BC behaviour is essential for avoiding any unwanted effects from the use of glucocorticoids in routine oncology practice.

  13. Clinical Significance of Molecular Diagnostic Tools for Bacterial Bloodstream Infections: A Systematic Review

    PubMed Central

    Nyirahabimana, Therese

    2016-01-01

    Bacterial bloodstream infection (bBSI) represents any form of invasiveness of the blood circulatory system caused by bacteria and can lead to death among critically ill patients. Thus, there is a need for rapid and accurate diagnosis and treatment of patients with septicemia. So far, different molecular diagnostic tools have been developed. The majority of these tools focus on amplification based techniques such as polymerase chain reaction (PCR) which allows the detection of nucleic acids (both DNA and small RNAs) that are specific to bacterial species and sequencing or nucleic acid hybridization that allows the detection of bacteria in order to reduce delay of appropriate antibiotic therapy. However, there is still a need to improve sensitivity of most molecular techniques to enhance their accuracy and allow exact and on time antibiotic therapy treatment. In this regard, we conducted a systematic review of the existing studies conducted in molecular diagnosis of bBSIs, with the main aim of reporting on clinical significance and benefits of molecular diagnosis to patients. We searched both Google Scholar and PubMed. In total, eighteen reviewed papers indicate that shift from conventional diagnostic methods to molecular tools is needed and would lead to accurate diagnosis and treatment of bBSI. PMID:27974890

  14. [Measurement of the reserve function of inspiratory muscle and its clinical significance].

    PubMed

    Xiao, X; Luo, Y; Chen, W; Yuan, Y; He, T; Zeng, J

    1995-06-01

    The principles of measuring inspiratory muscle tension-time index (TTim) and the ratio of the works of inspiration over the maximal works of inspiration (Wi/Wi(max)) were investigated and their formulae were deduced, i.e. TTim = (Pi x Ti)/(MIP x Ttot) and Wi/Wi(max) = (Pi x VT)/(MIP x IC). The importance of the inspiratory pressure and the maximal inspiratory pressure (MIP) measured at function residual capacity (FRC) level was emphasized. Both TTim and Wi/Wi(max) were measured in 35 normal subjects and 89 patients with chronic obstructive pulmonary disease (COPD). The results showed that normal value of TTim was 0.0253 +/- 0.0055 which corresponds to the normal value of the diaphragm tension-time index (TTdi = 0.02-0.03) reported by Bellemare. Patients with COPD had a mean TTim much higher than that of normals (P < 0.01). The works of inspiration (Wi) in patients with COPD increased, while the maximal works of inspiration (Wi(max)) declined, so Wi/Wi(max) became significantly greater than that of normals (P < 0.01). The results also showed that there was a linear relationship between Pi/Pimax and TTim or Wi/Wimax (r = 0.7891, 0.9738, 0.6459, 0.9327, P < 0.01). Therefore, we suggest that both TTim and Wi/Wimax can be used as clinical indices to reflect the reserve function of inspiratory muscles.

  15. The different functions and clinical significances of caveolin-1 in human adenocarcinoma and squamous cell carcinoma

    PubMed Central

    Fu, Pin; Chen, Fuchun; Pan, Qi; Zhao, Xianda; Zhao, Chen; Cho, William Chi-Shing; Chen, Honglei

    2017-01-01

    Caveolin-1 (Cav-1), a major structural protein of caveolae, is an integral membrane protein which plays an important role in the progression of carcinoma. However, whether Cav-1 acts as a tumor promoter or a tumor suppressor still remains controversial. For example, the tumor-promoting function of Cav-1 has been found in renal cancer, prostate cancer, tongue squamous cell carcinoma (SCC), lung SCC and bladder SCC. In contrast, Cav-1 also plays an inhibitory role in esophagus adenocarcinoma, lung adenocarcinoma and cutaneous SCC. The role of Cav-1 is still controversial in thyroid cancer, hepatocellular carcinoma, gastric adenocarcinoma, colon adenocarcinoma, breast cancer, pancreas cancer, oral SCC, laryngeal SCC, head and neck SCC, esophageal SCC and cervical SCC. Besides, it has been reported that the loss of stromal Cav-1 might predict poor prognosis in breast cancer, gastric cancer, pancreas cancer, prostate cancer, oral SCC and esophageal SCC. However, the accumulation of stromal Cav-1 has been found to be promoted by the progression of tongue SCC. Taken together, Cav-1 seems playing a different role in different cancer subtypes even of the same organ, as well as acting differently in the same cancer subtype of different organs. Thus, we hereby explore the functions of Cav-1 in human adenocarcinoma and SCC from the perspective of clinical significances and pathogenesis. We envision that novel targets may come with the further investigation of Cav-1 in carcinogenesis. PMID:28243118

  16. Endocannabinoid system as a regulator of tumor cell malignancy – biological pathways and clinical significance

    PubMed Central

    Pyszniak, Maria; Tabarkiewicz, Jacek; Łuszczki, Jarogniew J

    2016-01-01

    The endocannabinoid system (ECS) comprises cannabinoid receptors (CBs), endogenous cannabinoids, and enzymes responsible for their synthesis, transport, and degradation of (endo)cannabinoids. To date, two CBs, CB1 and CB2, have been characterized; however, orphan G-protein-coupled receptor GPR55 has been suggested to be the third putative CB. Several different types of cancer present abnormal expression of CBs, as well as other components of ECS, and this has been shown to correlate with the clinical outcome. Although most effects of (endo)cannabinoids are mediated through stimulation of classical CBs, they also interact with several molecules, either prosurvival or proapoptotic molecules. It should be noted that the mode of action of exogenous cannabinoids differs significantly from that of endocannabinoid and results from the studies on their activity both in vivo and in vitro could not be easily compared. This review highlights the main signaling pathways involved in the antitumor activity of cannabinoids and the influence of their activation on cancer cell biology. We also discuss changes in the expression pattern of the ECS in various cancer types that have an impact on disease progression and patient survival. A growing amount of experimental data imply possible exploitation of cannabinoids in cancer therapy. PMID:27486335

  17. Unilateral ectopic insertion of the pectoralis minor: Clinical and functional significance.

    PubMed

    Goldman, E; Vasan, C; Lopez-Cardona, H; Vasan, N

    2016-03-01

    During routine dissection of a 70-year-old female, we observed a unilateral ectopic insertion of the left pectoralis minor muscle. The tendon was cord-like and passed through a tendon sheath superior to the coracoid process to insert on the greater tubercle of the humerus. Additionally, an aponeurosis extended from the distal aspect of the muscle's tendon and passed medially to insert near the base of the coracoid process. This is the first report of an additional aponeurosis extending from the tendon of the pectoralis minor and attaching to the coracoid process. We also observed that the pectoralis minor tendon caused an unusually smooth deep indentation on the superior aspect of the coracoid process; considering its insertion on the humerus, we hypothesize that the muscle acted as an abductor of the shoulder along with the supraspinatus. The medial extension of an aponeurotic tendon from the pectoralis minor tendon near its insertion, to the base of the coracoid process further suggests that the muscle provided stability to the glenohumeral joint while acting as an abductor. Pectoralis minor variations have been described since 1897; however, few studies have demonstrated functional or clinical significance. The redundancy of the actions of this muscle along with its long tendon suggests a potential source for autograft.

  18. Effects of triamcinolone acetonide on microglial morphology and quantitative expression of MHC-II in exudative age-related macular degeneration.

    PubMed

    Penfold, P L; Wong, J G; Gyory, J; Billson, F A

    2001-06-01

    Animal models, in vitro assays and pilot clinical studies suggest that intravitreal triamcinolone acetonide may be useful in the treatment of age-related macular degeneration. The present case study reports the effect of intravitreal triamcinolone acetonide injection on a subretinal neovascular lesion, microglial morphology and quantitative expression of MHC-II antigens. Triamcinolone acetonide significantly decreased MHC-II expression consistent with immunocytochemical observations which revealed condensed microglial morphology. The modulation of subretinal oedema and microglial morphology correlates with in vitro observations suggesting that downregulation of inflammatory markers and endothelial cell permeability are significant features of the mode of action of triamcinolone acetonide.

  19. Clinical significance of the fractional excretion of anions in metabolic acidosis.

    PubMed

    Kim, H Y; Han, J S; Jeon, U S; Joo, K W; Earm, J H; Ahn, C; Kim, S; Lee, J S; Kim, G H

    2001-06-01

    The fractional excretion of anions has been proposed as a new index for the differential diagnosis of metabolic acidosis, identifying the properties of the conjugate base by examining the renal handling of the anion. Here, we investigated clinical significance of the fractional excretion of anions in pathophysiologic diagnosis of metabolic acidosis by measuring urine ammonium (NH4+) excretion, the ratio of A plasma anion gap/delta plasma HCO3- concentration (deltaAG/deltaHCO3-), and fractional excretion of anions in three different groups of metabolic acidosis: acid overproduction (8 patients with lactic acidosis, 8 with diabetic ketoacidosis, 3 with hippuric acidosis following glue sniffing), acid underexcretion (10 patients with chronic renal failure) and normal controls (10 normal volunteers who underwent 3-day NH4Cl loading). As expected, urine NH4+ excretion was higher in overproduction acidosis than in acid-loaded normal controls (88.1 +/- 12.3 vs. 54.0 +/- 3.7 mmol/day, p < 0.05), and it was lower in chronic renal failure than in acid-loaded normal controls (12.8 +/- 1.7 vs. 54.0 +/- 3.7 mmol/day, p < 0.05). The fractional excretion of anions had no difference between overproduction acidosis and chronic renal failure (41.2 +/- 42.8% vs. 41.0 +/- 8.1%). However, the fractional excretion of anions showed significant differences between the subgroups in acid overproduction (lactic acidosis, 4.7 +/- 0.3%; diabetic ketoacidosis, 45.8 +/- 3.1%; hippuric acidosis, 126.0 +/- 14.4%; p < 0.05). The ratio of plasma deltaAG/deltaHCO3- also exhibited significant differences between the subgroups in acid overproduction (lactic acidosis, 1.5 +/- 0.1; diabetic ketoacidosis, 1.0 +/- 0.1; hippuric acidosis, 0.3 +/- 0.1; p < 0.05). There was an inverse linear correlation between the fractional excretion of anions and the ratio of plasma deltaAG/deltaHCO3- (r2 =-0.89, p < 0.05). In conclusion, determination of the fractional excretion of anions may provide a useful clue to the

  20. The Frequency and Clinical Significance of IDH1 Mutations in Chinese Acute Myeloid Leukemia Patients

    PubMed Central

    Wang, Lili; Li, Meng; Yin, Yue; Yu, Li; Gao, Chunji

    2013-01-01

    Objective Mutations in the gene encoding isocitrate dehydrogenease 1 (IDH1) occur in various hematopoietic tumors including acute myeloid leukemia (AML), myeloproliferative neoplasms and myelodysplastic syndromes. IDH1 mutations are significant in both diagnosis and prognosis of these conditions. In the present study we determined the prevalence and clinical significance of IDH1 mutations in 349 samples from newly diagnosed AML patients. Results Of the 349 AML patient specimens analyzed, 35 (10.03%) were found to have IDH1 mutations including 4 IDH1 R132 mutations and 31 non-R132 mutations. IDH1 non-R132 mutations were largely concentrated within AML-M1 (35.72%, p<0.01). We identified five IDH1 mutations that were novel to AML: (1) c.299 G>A, p.R100Q; (2) c.311G>T, p.G104V; (3) c.322T>C, p.F108L; (4) c.356G>A, p.R119Q; and (5) c.388A>G, p.I130V. In addition, we identified three IDH1 mutations that were previously described in AML. The frequency of IDH1 mutations in AML patients with normal karyotype was 9.9%. IDH1 non-R132 mutations were concurrent with mutations in FLT3-ITD (p<0.01), CEBPA (p<0.01), and NRAS (p<0.01), as well as the overexpression of MN1 (p<0.01) and WT1(p<0.01). The overall survival (OS) in the patients with IDH1 non-R132 mutations compared to patients without IDH1 mutations don't reach statistically significance (median 521 days vs median: not reached; n.s.). Conclusion IDH1 non-R132 mutations occurred frequently in newly diagnosed adult Chinese AML patients, and these mutations were associated with genetic alterations. The OS was not influenced by IDH1 non-R132 mutations in the present study. PMID:24376688

  1. Markers of stem cells in human ovarian granulosa cells: is there a clinical significance in ART?

    PubMed Central

    2012-01-01

    Background The purpose of the study was to determine the incidence of gene expression of Oct-4 and DAZL, which are typical markers for stem cells, in human granulosa cells during ovarian stimulation in women with normal FSH levels undergoing IVF or ICSI and to discover any clinical significance of such expression in ART. Methods Twenty one women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded separately and granulosa cells were analyzed for each patient separately using quantitative reverse-transcription–polymerase chain reaction analysis for Oct-4 and DAZL gene expression with G6PD gene as internal standard. Results G6PD and Oct-4 mRNA was detected in the granulosa cells in 47.6% (10/21). The median of Oct-4 mRNA/G6PD mRNA was 1.75 with intra-quarteral range from 0.10 to 98.21. The OCT-4 mRNA expression was statistically significantly correlated with the number of oocytes retrieved; when the Oct-4 mRNA expression was higher, then more than six oocytes were retrieved (p=0.037, Wilcoxon rank-sum). No detection of DAZL mRNA was found in granulosa cells. There was no additional statistically significant correlation between the levels of Oct-4 expression and FSH basal levels or estradiol peak levels or dosage of FSH for ovulation induction. No association was found between the presence or absence of Oct-4 mRNA expression in granulosa cells and ovarian response to gonadotropin stimulation. Also, no influence on pregnancy was observed between the presence or absence of Oct-4 mRNA expression in granulosa cells or to its expression levels accordingly. Conclusions Expression of OCT-4 mRNA, which is a typical stem cell marker and absence of expression of DAZL mRNA, which is a typical germ cell marker, suggest that a subpopulation of luteinized granulosa cells in healthy ovarian follicles (47.6%) consists of stem cells

  2. Clinically significant drug interactions among HIV-infected patients receiving antiretroviral therapy.

    PubMed

    So-Ngern, Apichot; Montakantikul, Preecha; Manosuthi, Weerawat

    2014-09-01

    We conducted a cross sectional study of the outpatient medical records of 1000 HIV-infected patients receiving antiretroviral therapy (ART) in 2011 to determine the incidence of clinically significant drug interactions (CSDI). The severities of the CSDI were graded following the Micromedex" 2.0 database and the Department of Health and Human Services (DHHS) 2012 HIV treatment guidelines. Three hundred thirty-five patients (34%) had 554 episodes of CSDI. Of which 337 episodes (61%), 163 episodes (29%) and 54 episodes (10%) had grades 2, 3 and 4 severity CSDI, respectively. The CSDI were caused by protease inhibitor (PI)-based drug regimens in 79%, by efavirenz-based regimens in 34% and by nevirapine-based regimens in 10% (p<0.001). The three most common grade 4 CSDI were: a PI with simvastatin (n=24), simvastatin with gemfibrozil (n=24) and didanosine with allopurinol (n=2). The three most common grade 3 CSDI were: a PI with a statin drug except simvastatin (n=56), fenofibrate with a statin drug (n=28) and amlodipine with simvastatin (n=14). On multivariate analysis, risk factors associated with CSDI were: receiving a PI-based regimen (OR 14.44; 95% CI: 9.10-22.88), having dyslipidemia (OR 3.94; 95% CI: 1.89-8.21), having >5 items prescribed at a time (OR 1.80; 95% CI: 1.23-2.63), seeing a doctor >4 times a year (OR 1.72; 95% CI: 1.20-2.46), having hypertension (OR 0.60; 95% CI: 0.37-0.98), having a duration of receiving ART of >5 years (OR 0.46; 95% CI: 0.28-0.77) and having a CD4 count of >200 cells/mm3 (OR 0.46; 95%CI: 0.26-0.84). CSDI were common among HIV-infected patients receiving ARV in our outpatient clinic. Patients having a low CD, count, having dyslipidemia, receiving PI-based ART, having a frequent number of visits per year and having a large number of items prescribed at each visit had a greater chance of a CSDI.

  3. [The significance, development and prospects of healthcare data integration in new drug clinical trials].

    PubMed

    Cai, Hong-wei; Li, Yan-hong; Zhang, Zi-bao; Deng, Ya-zhong

    2015-11-01

    With the deployment of electronic medical records systems, more and more routine clinical data are recorded electronically, which become a potential data source for new drug clinical trials. In this paper, we summarized the opportunities, challenges, obstacles and the latest development in this field.

  4. Efficacy of single bevacizumab injection as adjuvant therapy to laser photocoagulation in macular edema secondary to branch retinal vein occlusion

    PubMed Central

    Kartasasmita, Arief S; Takarai, Siska; Switania, Astriviani; Enus, Sutarya

    2016-01-01

    Background Macular grid laser photocoagulation remains the standard treatment for macular edema secondary to branch retinal vein occlusion (BRVO). One possible strategy for treating macular edema is to inhibit VEGF activity by competitive binding of VEGF with an anti-VEGF antibody, suggesting the therapy option with bevacizumab. However, multiple injections of anti-VEGF may lead to complications and high cost. Purpose The aim of this study was to evaluate the improvement in visual acuity and central macular thickness after combination therapy of laser photocoagulation with single intravitreal bevacizumab injection in macular edema secondary to BRVO. Methods Nineteen patients with macular edema secondary to BRVO were assigned to either the group of nine patients in combination therapy of laser photocoagulation with intravitreal bevacizumab or the group of ten patients in the laser photocoagulation therapy. Complete ophthalmologic examinations were performed just before the therapy and at 1 month following the therapy. Changes in visual acuity were tested with the logarithm of minimum angle of resolution (logMAR), and central macular thickness was measured by optical coherence tomography (OCT). Results Combination therapy of laser photocoagulation and single intravitreal bevacizumab injection resulted in a significantly better visual acuity compared to laser photocoagulation therapy (0.35 versus 0.13 logMAR; P=0.041) and reduced macular thickness by 120.33 µm versus 71.50 µm (P=0.277), although this difference was not significant. Conclusion Laser photocoagulation combined with a single intravitreal bevacizumab has a substantial effect on increasing visual acuity in macular edema secondary to BRVO. PMID:27826179

  5. Progressive macular hypomelanosis among Egyptian patients: a clinicopathological study

    PubMed Central

    Selim, Mohamed Khaled; Ahmed, El-Shahat Farag; Abdelgawad, Mamdouh Morsy; El-Kamel, Mohammed Fawzy

    2011-01-01

    Background: Progressive macular hypomelanosis (PMH) is a disease of unclear etiology. Propionbacterium acnes (P. acnes) was claimed to be an etiological factor. Objectives: The purpose of this study was to document the clinicopathological features of PMH in Egyptian patients and to evaluate the therapeutic outcome. Methods: Patients with clinical features of PMH were recruited. Wood’s lamp examination, skin scrapings for fungi, and skin biopsy specimens were obtained. Biopsies were stained with hematoxylin and eosin, PAS, Fontana-Masson, and S100 protein. Patients received either narrow-band UVB (nbUVB) or nbUVB plus daily topical clindamycin 1% and benzoyl peroxide gel 5% (bcUVB). The period of active treatment was 14 weeks followed by a follow-up period of 24 weeks. Results: Twenty-nine patients were included. Microscopic evaluation of skin biopsy specimens showed no significant differences between lesional and normal skin. Fontana-Masson stained sections showed overall reduction of melanin granules in the basal layer of lesional skin only and S100 staining did not detect significant differences in the number of melanocytes in lesional and normal skin. Nearly complete repigmentation was reported in 10 patients treated with bcUVB compared to 9 patients treated with nbUVb with no significant differences between both groups after 14 weeks. Only 2 patients in each group retained the pigmentation and the remaining patients returned to the baseline color before treatment. Conclusions: This study documented the clinicopathological features of PMH among Egyptians. No permanently effective treatment is available. Further studies are needed to prove or disprove the pathogenic role of P. acnes in PMH. PMID:24396712

  6. Vitrectomy for center-involved diabetic macular edema

    PubMed Central

    Browning, David J; Lee, Chong; Stewart, Michael W; Landers, Maurice B

    2016-01-01

    Purpose To determine the effect of vitrectomy for center-involved diabetic macular edema (CI-DME). Methods This was a retrospective study of 53 eyes of 45 patients who had vitrectomy for CI-DME and were followed up for at least 12 months. Charts were reviewed for visual acuity (VA), central subfield mean thickness measured by optical coherence tomography, presurgical and postsurgical interventions for CI-DME, and number of office visits in the first 12 months after surgery. Preoperative spectral domain optical coherence tomography was performed on 38 patients, and they were graded for ellipsoid zone (EZ) intactness by three independent graders with assessment of agreement between graders using intraclass correlation coefficients and Bland–Altman analysis. Results The median VA improved from 20/100 (interquartile range [IQR], 20/63–20/200) at baseline to 20/63 (IQR, 20/32–20/125) at 12 months. The median central subfield mean thickness improved from 505 μm (IQR, 389–597 μm) at baseline to 279 μm (IQR, 246–339 μm) at 12 months. Intergrader agreement for EZ intactness was moderate (intraclass correlation coefficients 0.4294–0.6356). There was no relationship between preoperative intactness of the EZ and the 12-month change in VA. Conclusion Vitrectomy consistently thins the macula in CI-DME and, on average, leads to clinically significant improvement in VA comparable in size to that reported with serial intravitreal anti-vascular endothelial growth factor injections. A large, comparative, prospective, randomized clinical trial of these two treatments is needed to determine which is more effective and cost-effective. PMID:27175056

  7. Biological and clinical significance of tryptophan-catabolizing enzymes in cutaneous T-cell lymphomas

    PubMed Central

    Maliniemi, Pilvi; Dettmer, Katja; Lipsanen, Tuomas; Jeskanen, Leila; Bessede, Alban; Oefner, Peter J.; Kadin, Marshall E.

    2017-01-01

    ABSTRACT Indoleamine 2,3-deoxygenase 1 (IDO1) induces immune tolerance in the tumor microenvironment (TME) and is recognized as a potential therapeutic target. We studied the expression of both IDO1 and the related tryptophan 2,3-dioxygenase (TDO) in several different subtypes of cutaneous T-cell lymphoma (CTCL), and evaluated the kynurenine (KYN) pathway in the local TME and in patient sera. Specimens from the total of 90 CTCL patients, including mycosis fungoides (MF, n = 37), lymphomatoid papulosis (LyP, n = 36), primary cutaneous anaplastic large cell lymphoma (pcALCL, n = 4), subcutaneous panniculitis-like T-cell lymphoma (SPTCL n = 13), and 10 patients with inflammatory lichen ruber planus (LRP), were analyzed by immunohistochemistry (IHC), immunofluorescence (IF), quantitative PCR, and/or liquid chromatography–tandem mass spectrometry (LC–MS/MS). Three CTCL cell lines also were studied. Expression of both IDO1 and TDO was upregulated in CTCL. In MF specimens and in the MF cell line MyLa2000, IDO1 expression exceeded that of TDO, whereas the opposite was true for LyP, ALCL, and corresponding Mac1/2A cell lines. The spectrum of IDO1-expressing cell types differed among CTCL subtypes and was reflected in the clinical behavior. In MF, SPTCL, and LyP, IDO1 was expressed by malignant cells and by CD33+ myeloid-derived suppressor cells, whereas in SPTCL CD163+ tumor-associated macrophages also expressed IDO1. Significantly elevated serum KYN/Trp ratios were found in patients with advanced stages of MF. Epacadostat, an IDO1 inhibitor, induced a clear decrease in KYN concentration in cell culture. These results show the importance of IDO1/TDO-induced immunosuppression in CTCL and emphasize its role as a new therapeutic target.

  8. Pathogenic features of clinically significant coagulase-negative staphylococci in hospital and community infections in Benin.

    PubMed

    Nanoukon, Chimène; Argemi, Xavier; Sogbo, Frédéric; Orekan, Jeanne; Keller, Daniel; Affolabi, Dissou; Schramm, Frédéric; Riegel, Philippe; Baba-Moussa, Lamine; Prévost, Gilles

    2017-01-01

    In West Africa, very little consideration has been given to coagulase negative Staphylococci (CNS). Herein, we describe the features contributing to the pathogenicity of 99 clinically-significant independent CNS isolates associated with infections encountered at the National Teaching Hospital Center of Cotonou (Benin). The pathogenic potentials of nosocomial strains were compared with community strains. S. haemolyticus (44%), S. epidermidis (22%) and S. hominis (7%) were the most frequently isolated while bacteremia (66.7%) and urinary tract infections (24.2%) were the most commonly encountered infections. Most strains were resistant to multiple antibiotics, including penicillin (92%), fosfomycin (81%), methicillin (74%) and trimethoprim-sulfamethoxazole (72%). The most frequently isolated species were also the most frequently resistant to methicillin: S. hominis (100%), S. haemolyticus (93%) and S. epidermidis (67%). Screening of toxic functions or toxin presence revealed hemolytic potential in 25% of strains in over 50% of human erythrocytes in 1h. Twenty-six percent of strains exhibited protease activity with low (5%), moderate (10%) and high activity (11%), while 25% of strains displayed esterase activity. Three percent of strain supernatants were able to lyse 100% of human polymorphonuclear cells after 30min. Polymerase chain reaction and latex agglutination methods revealed staphylococcal enterotoxin C gene expression in 9% of S. epidermidis. A majority of hospital-associated CNS strains (68%) had at least one important virulence feature, compared with only 32% for community-acquired strains. The present investigation confirms that these microorganisms can be virulent, at least in some individual cases, possibly through genetic transfer from S. aureus.

  9. Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML.

    PubMed

    DiNardo, Courtney D; Ravandi, Farhad; Agresta, Sam; Konopleva, Marina; Takahashi, Koichi; Kadia, Tapan; Routbort, Mark; Patel, Keyur P; Mark Brandt; Pierce, Sherry; Garcia-Manero, Guillermo; Cortes, Jorge; Kantarjian, Hagop

    2015-08-01

    The pathophysiology of IDH mutations in tumorigenesis is increasingly described, yet the prognostic significance of IDH1 and IDH2 mutations in AML remains controversial. The primary objective of this study was to define the natural history and prognosis of patients with AML and IDH1 or IDH2 mutations and provide historical survival expectations. A total of 826 patients treated from 2010 to 2014 at a single institution were evaluated, including 167 patients (20%) with AML and IDH1 or IDH2 mutations. Median age was 62 years (range 18-92). There were 59 IDH1-R132, 83 IDH2-R140, and 23 IDH2-R172 mutations. Clinicopathologic characteristics associated with IDH-mutations included older age, less frequent therapy-related status, and increased incidence of intermediate-risk cytogenetics, FLT3-ITD mutations, and NPM1 mutations. Remission rates (CR/CRi) by AML treatment status were: induction, 68%; Salvage-1 (S1), 42%; and Salvage-2 and beyond (S2+), 27%. No difference in response was identified by IDH mutation status. Similarly, overall survival (OS) was not dependent on IDH status within any cohort. The median OS was 15.4 months in induction, 8.7 months in S1, and 4.8 months in S2+. This analysis defines the clinical outcome associated with IDH-mutations in both the front-line and salvage AML treatment settings, and confirms that response rate and OS for both IDH-mutated and IDH wild-type AML patients is comparable. This provides contemporary data to be used for comparison with results of novel investigational (e.g., selective IDH inhibitor) strategies.

  10. Clinical significance of systematic retroperitoneal lymphadenectomy during interval debulking surgery in advanced ovarian cancer patients

    PubMed Central

    Takada, Toshio; Iitsuka, Chiaki; Nomura, Hidetaka; Abe, Akiko; Taniguchi, Tomoko; Takizawa, Ken

    2015-01-01

    Objective To investigate the clinical significance of systematic retroperitoneal lymphadenectomy during interval debulking surgery (IDS) in advanced epithelial ovarian cancer (EOC) patients. Methods We retrospectively reviewed the medical records of 124 advanced EOC patients and analyzed the details of neoadjuvant chemotherapy (NACT), IDS, postoperative treatment, and prognoses. Results Following IDS, 98 patients had no gross residual disease (NGRD), 15 had residual disease sized <1 cm (optimal), and 11 had residual disease sized ≥1 cm (suboptimal). Two-year overall survival (OS) and progression-free survival (PFS) rates were 88.8% and 39.8% in the NGRD group, 40.0% and 13.3% in the optimal group (p<0.001 vs. NGRD for both), and 36.3% and 0% in the suboptimal group, respectively. Five-year OS and 2-year PFS rates were 62% and 56.1% in the lymph node-negative (LN-) group and 26.2% and 24.5% in the lymph node-positive (LN+) group (p=0.0033 and p=0.0024 vs. LN-, respectively). Furthermore, survival in the LN+ group, despite surgical removal of positive nodes, was the same as that in the unknown LN status group, in which lymphadenectomy was not performed (p=0.616 and p=0.895, respectively). Multivariate analysis identified gross residual tumor during IDS (hazard ratio, 3.68; 95% confidence interval, 1.31 to 10.33 vs. NGRD) as the only independent predictor of poor OS. Conclusion NGRD after IDS improved prognosis in advanced EOC patients treated with NACT-IDS. However, while systematic retroperitoneal lymphadenectomy during IDS may predict outcome, it does not confer therapeutic benefits. PMID:26197771

  11. Clinical significance of sunitinib-associated macrocytosis in metastatic renal cell carcinoma.

    PubMed

    Bourlon, Maria T; Gao, Dexiang; Trigero, Sara; Clemons, Julia E; Breaker, Kathryn; Lam, Elaine T; Flaig, Thomas W

    2016-12-01

    Increases in the mean corpuscular volume (MCV) have been observed in patients with metastatic renal cell carcinoma (mRCC) on tyrosine kinase inhibitor (TKI) treatment; however, its association with progression-free-survival (PFS) is unknown. We aimed to characterize TKI-associated macrocytosis in mRCC and its relationship with PFS. Retrospective review of data on macrocytosis and thyroid dysfunction on mRCC patients treated with sunitinib and/or sorafenib. These results are evaluated in the context of our previous report on the association of hypothyroidism in this setting. We assessed PFS as clinically defined by the treating physician. Seventy-four patients, 29 of whom received both drugs, were included. A treatment period was defined as time from initiation to discontinuation of either sunitinib or sorafenib; 103 treatment periods [sorafenib (47), sunitinib (56)] were analyzed. Macrocytosis was found in 55 and 8% of sunitinib- and sorafenib-treated patients, respectively, P < 0.001. The median time to developing macrocytosis was 3 months (m, range 1-7). Median PFS in sunitinib-treated patients was 11 m (95% CI: 6-19). Median PFS was higher among those with macrocytosis compared to normocytosis (21 m [95% CI: 11-25] vs. 4 m [95% CI: 3-8] P = 0.0001). Macrocytosis and hypothyroidism were two significant predictors of PFS. The greatest difference in PFS among all patients was observed in patients with both macrocytosis and hypothyroidism (25 m), compared to the normocytic and euthyroid patients (5 m) (P < 0.0001). Sunitinib-related macrocytosis was associated with prolonged PFS, and concurrent development of hypothyroidism and macrocytosis further prolonged PFS. Increased MCV may have a role as a predictive biomarker for sunitinib. Prospective studies accounting for other known prognostic factors are needed to confirm this finding.

  12. Comparison of Modified-ETDRS and Mild Macular Grid Laser Photocoagulation Strategies for Diabetic Macular Edema

    PubMed Central

    2008-01-01

    more extensively evaluated current mETDRS laser photocoagulation approach. However, the visual acuity outcome with both approaches is not substantially different. Given these findings a larger long-term trial of the MMG technique is not justified. Application to Clinical Practice Modified ETDRS focal photocoagulation should continue as a standard approach for treating diabetic macular edema. PMID:17420366

  13. [Macular coloboma type Leber's congenital amaurosis].

    PubMed

    Kiratli, H; Bozkurt, B

    2002-01-01

    Three brothers, with the macular coloboma type Leber's congenital amaurosis aged 10, 8, and 6 years respectively, are described in this report. Only the two elder brothers were symptomatic while the third patient had no complaint at the time of diagnosis. The patients had no associated systemic or ocular disorders, including nystagmus. They had mild myopic astigmatism. All three had a relatively well-circumscribed bilateral macular atrophy with a seemingly normal peripheral retina. The electroretinogram was non recordable but the visualy evoked potential responses were within normal limits. During three years of follow-up, the macular lesions did not progress and the visual acuity did not deteriorate further. Our experience with these three familial cases supports the general view that the macular coloboma variant does not necessarily have the typical signs and symptoms and perhaps also the dismal prognosis of classic Leber's congenital amaurosis, and as such should stand as a distinct subtype of the disease.

  14. Genetics Home Reference: vitelliform macular dystrophy

    MedlinePlus

    ... faces. Vitelliform macular dystrophy causes a fatty yellow pigment (lipofuscin) to build up in cells underlying the ... structures in these cells that contain light-sensing pigments. It is unclear why PRPH2 mutations affect only ...

  15. Managed care implications of diabetic macular edema.

    PubMed

    Holekamp, Nancy M

    2016-07-01

    Diabetic retinopathy (DR) is both the leading cause of blindness among adults aged 20 to 74 in the United States, and the leading ocular complication associated with diabetes mellitus (DM). An estimated 4.4% of adults with DM over 40 years of age have the more advanced form of DR: diabetic macular edema (DME), which significantly increases the risk of blindness. Medical costs for Medicare patients with DME are a third higher than for patients without DME. The majority of these costs stem from other DM-related complications, as DME is a marker for poorly controlled DM overall. Commercially insured patients with DME incur direct and indirect costs up to 75% higher than for those with DR without DME. Early detection, treatment, and improved glycemic control can limit the onset or progression of microvascular complications of DR, including DME, resulting in significant savings for payers. However, there are significant gaps in adherence to national guidelines regarding DM control and early identification of DR. In addition, patients face several barriers to screening. Improving screening for and management of early DR could decrease progression to DME, which would provide significant savings for payers, as well as improve the quality of care and outcomes for patients with DM. Managed care organizations and employers should also consider the cost-effectiveness of currently available treatments for DME: focal laser photocoagulation, vascular endothelial growth factor inhibitors, and intravitreal corticosteroid injections and implants, in their formulary design; they should also identify opportunities to improve patient adherence to treatment.

  16. Flicker fusion thresholds in Best macular dystrophy.

    PubMed

    Massof, R W; Fleischman, J A; Fine, S L; Yoder, F

    1977-06-01

    Flicker fusion threshold intensities were measured as a function of flicker frequency for patients with Best macular dystrophy having normal or near-normal Snellen visual acuity. These data were found to differ from normal in ways that may be interpreted to be an abnormal elevation of the foveal cone threshold, a loss of cone temporal resolution, or both. The results led to the conclusion that Best macular dystrophy affects the neurosensory retina even when Snellen visual acuity is normal.

  17. De Garengeot's hernia in an 82-year-old man: a case report and clinical significance

    PubMed Central

    Leite, Túlio F.; Chagas, Carlos A.A.; Pires, Lucas A.S.; Cisne, Rafael; Babinski, Márcio A.

    2016-01-01

    The presence of the appendix within a femoral hernia (FH) sac is known as Garengeot's hernia (GH). We report on current study a rare case of an elderly man with a combined inguinal and Garengeot's hernia and discuss the clinical aspects. An 82-year-old man clinically stable, presented history of pain at the right inguinal region for over a week, without vomit, nausea, fever or any alteration of intestinal or urinary eliminations. Clinical examination revealed a FH and the ultrasonography confirmed the hernia sac. During the surgery, the appendix was recognized within the sac, and then, the patient underwent appendectomy and hernia repair. In conclusion, the presence of the vermiform appendix in a FH sac is rare, thus, requiring knowledge of the surgeon regarding this clinical entity. Prompt diagnosis and appropriate surgical treatment is the key to avoid complications. PMID:27381019

  18. Lies, damned lies and statistics: Clinical importance versus statistical significance in research.

    PubMed

    Mellis, Craig

    2017-02-28

    Correctly performed and interpreted statistics play a crucial role for both those who 'produce' clinical research, and for those who 'consume' this research. Unfortunately, however, there are many misunderstandings and misinterpretations of statistics by both groups. In particular, there is a widespread lack of appreciation for the severe limitations with p values. This is a particular problem with small sample sizes and low event rates - common features of many published clinical trials. These issues have resulted in increasing numbers of false positive clinical trials (false 'discoveries'), and the well-publicised inability to replicate many of the findings. While chance clearly plays a role in these errors, many more are due to either poorly performed or badly misinterpreted statistics. Consequently, it is essential that whenever p values appear, these need be accompanied by both 95% confidence limits and effect sizes. These will enable readers to immediately assess the plausible range of results, and whether or not the effect is clinically meaningful.

  19. Overview of diabetic macular edema.

    PubMed

    Holekamp, Nancy M

    2016-07-01

    Diabetes mellitus (DM) is a rapidly growing epidemic in the United States, and it is expected to affect 592 million individuals within the next 20 years. Diabetic retinopathy (DR) and diabetic macular edema (DME) are the 2 most common ophthalmic complications of DM. DR is the leading cause of blindness among working-age adults around the world, and development of DR is tied to DM disease duration. With the only identifier of early markers of DR being a complete ophthalmic exam, early signs of the disease are asymptomatic. Yearly, or at least every other year, ophthalmic exams are recommended for all patients with DM; but often, individuals with DM have not undergone screening exams and do not have regular eye exams until vision loss has occurred. With spending estimates of $490 million to treat the vision complications of DM, it is clear that DR and DME impose a substantial burden for patients, caregivers, and healthcare systems.

  20. [The Coordinating Centres for Clinical Trials Network. Objectives and significance for research sites].

    PubMed

    Bruns, I; Maier-Lenz, H; Wolff, S

    2009-04-01

    In the late 1990s a funding program was set up by the federal German government to help keep stride with developments in the international research arena. Within this programme, Coordinating Centres for Clinical Trials ("Koordinierungszentren für Klinische Studien", KKS) were established at 12 German universities aiming at supporting all processes of academic clinical trials according to international standards. A close network infrastructure was chosen in order to reap maximum benefit from synergy effects and to promote the harmonisation of standards. Continuing to grow, the KKS Network currently has 16 research institutions as members. More than 400 employees within the KKS Network provide scientific services to clinical trials at universities, hospitals and in industry. In cooperation with study clinics, surgeries, study groups and competence networks in medicine within Europe and beyond, the KKS supports many different research projects covering all areas of medicine. The KKS Network contributes expertise to legislative processes within Germany and Europe through its work in professional committees and working groups. A wide range of education and training concepts supports clinical research as a scientific field in its own right. After nearly ten years the KKS Network has established itself as an indispensable partner in the field of clinical research.

  1. Advanced image processing for optical coherence tomographic angiography of macular diseases

    PubMed Central

    Zhang, Miao; Wang, Jie; Pechauer, Alex D.; Hwang, Thomas S.; Gao, Simon S.; Liu, Liang; Liu, Li; Bailey, Steven T.; Wilson, David J.; Huang, David; Jia, Yali

    2015-01-01

    This article provides an overview of advanced image processing for three dimensional (3D) optical coherence tomographic (OCT) angiography of macular diseases, including age-related macular degeneration (AMD) and diabetic retinopathy (DR). A fast automated retinal layers segmentation algorithm using directional graph search was introduced to separates 3D flow data into different layers in the presence of pathologies. Intelligent manual correction methods are also systematically addressed which can be done rapidly on a single frame and then automatically propagated to full 3D volume with accuracy better than 1 pixel. Methods to visualize and analyze the abnormalities including retinal and choroidal neovascularization, retinal ischemia, and macular edema were presented to facilitate the clinical use of OCT angiography. PMID:26713185

  2. [Role of immunological factors in peripheral vitreo-chorioretinal dystrophies and macular ruptures of the retina].

    PubMed

    Balashova, L M; Saksonova, E O; Zaĭtseva, N S; Slepova, O S; Teplinskaia, L E; Il'nitskiĭ, V V; Grishin, V L

    1995-01-01

    The authors analyze the results of clinical and immunological examinations of patients with peripheral vitreo-chorioretinal dystrophies (PVCRD) and macular ruptures of the retina. No antibodies to S-AG were detected in the lacrimal fluid in 87.5% of patients with PVCRD without retinal defects. In patients with PVCRD with retinal defects antibodies to S-AG were detected in 70% of cases. These antibodies were absent in the patients with macular ruptures of the retina. In none of the patients were these antibodies detected in the blood serum. The levels of circulating immune complexes were normal in the patients PVCRD and increased in those with macular ruptures of the retina. These data permit a hypothesis on the development of local autoimmune reactions in PVCRD patients in response to the appearance of AG of the injured tissues.

  3. Autologous Induced Stem-Cell-Derived Retinal Cells for Macular Degeneration.

    PubMed

    Mandai, Michiko; Watanabe, Akira; Kurimoto, Yasuo; Hirami, Yasuhiko; Morinaga, Chikako; Daimon, Takashi; Fujihara, Masashi; Akimaru, Hiroshi; Sakai, Noriko; Shibata, Yumiko; Terada, Motoki; Nomiya, Yui; Tanishima, Shigeki; Nakamura, Masahiro; Kamao, Hiroyuki; Sugita, Sunao; Onishi, Akishi; Ito, Tomoko; Fujita, Kanako; Kawamata, Shin; Go, Masahiro J; Shinohara, Chikara; Hata, Ken-Ichiro; Sawada, Masanori; Yamamoto, Midori; Ohta, Sachiko; Ohara, Yasuo; Yoshida, Kenichi; Kuwahara, Junko; Kitano, Yuko; Amano, Naoki; Umekage, Masafumi; Kitaoka, Fumiyo; Tanaka, Azusa; Okada, Chihiro; Takasu, Naoko; Ogawa, Seishi; Yamanaka, Shinya; Takahashi, Masayo

    2017-03-16

    We assessed the feasibility of transplanting a sheet of retinal pigment epithelial (RPE) cells differentiated from induced pluripotent stem cells (iPSCs) in a patient with neovascular age-related macular degeneration. The iPSCs were generated from skin fibroblasts obtained from two patients with advanced neovascular age-related macular degeneration and were differentiated into RPE cells. The RPE cells and the iPSCs from which they were derived were subject to extensive testing. A surgery that included the removal of the neovascular membrane and transplantation of the autologous iPSC-derived RPE cell sheet under the retina was performed in one of the patients. At 1 year after surgery, the transplanted sheet remained intact, best corrected visual acuity had not improved or worsened, and cystoid macular edema was present. (Funded by Highway Program for Realization of Regenerative Medicine and others; University Hospital Medical Information Network Clinical Trials Registry [UMIN-CTR] number, UMIN000011929 .).

  4. Neuroblastoma and bone metastases: clinical significance and prognostic value of Dickkopf 1 plasma levels.

    PubMed

    Granchi, Donatella; Corrias, Maria Valeria; Garaventa, Alberto; Baglìo, Serena Rubina; Cangemi, Giuliana; Carlini, Barbara; Paolucci, Paolo; Giunti, Armando; Baldini, Nicola

    2011-01-01

    The critical role of the Wnt pathway inhibition in sustaining the onset of bone lesions has been demonstrated in a variety of bone diseases and tumors, and it has been associated with cancer aggressiveness. We have previously demonstrated that neuroblastoma cells express Dickkopf 1 (Dkk1), an inhibitor of the canonical Wnt pathway which prevents the differentiation of bone-forming cells. Since Dkk1 is a secreted factor, it could have potential clinical application as tumor marker for detecting bone metastasis and monitoring of disease. In this study, we investigated the diagnostic and prognostic value of Dkk1 plasma levels in 92 children affected by neuroblastoma, including 32 with bone metastases. Fifty-seven children hospitalized for minor surgical problems served as control group. Circulating levels of Dkk1 were higher in healthy children than in normal adults and were comparable to those found in adult patients with aggressive tumors. No significant differences were found between neuroblastoma patients and controls and between patients with and without bone metastases. However, when only patients with metastatic neuroblastoma were considered, the highest Dkk1 levels were detected in patients that poorly responded to induction chemotherapy and in subjects with unamplified MYCN and three or more different metastatic sites. The 'Receiver Operating Characteristic' curve enabled us to identify a threshold value to distinguish patients who were unresponsive to induction treatment. The relationship between Dkk1 and drug resistance was supported by in vitro experiments, since an increased sensitivity to doxorubicin was found in neuroblastoma cells releasing low Dkk1 levels, either constitutively or experimentally following the treatment with specific siRNA. In conclusion, Dkk1 is released by neuroblastoma cells and is able to affect the balance between osteoblastogenesis and osteoclastogenesis, thus favoring the onset of osteolytic metastases. Nevertheless, Dkk1 plasma

  5. Clinically significant differences in acute pain measured on self-report pain scales in children

    PubMed Central

    Tsze, Daniel S.; Hirschfeld, Gerrit; von Baeyer, Carl L.; Bulloch, Blake; Dayan, Peter S.

    2015-01-01

    Objectives The objective was to determine the minimum and ideal clinically significant differences (MCSD, ICSD) of the Faces Pain Scale–Revised (FPS-R) and the Color Analog Scale (CAS) in children and to identify any differences in these estimates based on patient characteristics. Methods This was a prospective study of children aged 4 to 17 years with acute pain presenting to two urban pediatric emergency departments. Participants self-reported their pain severity using the FPS-R and CAS and qualitatively described their changes in pain. Changes in pain score reported using the FPS-R and CAS that were associated with “a little less” and “much less” pain (MCSD and ICSD, respectively) were identified using a receiver operating characteristic–based method and expressed as raw change score and percent reductions. Estimates of MCSD and ICSD were determined for each category of initial pain severity (mild, moderate, and severe) and patient characteristics (age, sex, and ethnicity). Post hoc exploratory analyses evaluated categories of race, primary language, and etiology of pain. Results A total of 314 children with acute pain were enrolled; mean (±SD) age was 9.8 (±3.8) years. The FPS-R raw change score and percent reduction MCSD estimates were 2/10 and 25%, with ICSD estimates of 3/10 and 60%. For the CAS, raw change score and percent reduction MCSD estimates were 1/10 and 15%, with ICSD estimates of 2.75/10 and 52%. For both scales, raw change score and percent reduction estimates of the MCSD remained unchanged in children with either moderate or severe pain. For both scales, estimates of ICSD were not stable across categories of initial pain severity. There was no difference in MCSD or ICSD based on age, sex, ethnicity, race, primary language, or etiology of pain. Conclusions The MCSD estimates can be expressed as raw change score and percent reductions for the FPS-R and CAS. These estimates appear stable for children with moderate to severe pain

  6. Long-term effectiveness of ranibizumab for age-related macular degeneration and diabetic macular edema.

    PubMed

    Fong, Angie H C; Lai, Timothy Y Y

    2013-01-01

    Neovascular age-related macular degeneration (AMD) and diabetic macular edema (DME) are major causes of visual impairment in the elderly population worldwide. With the aging population, the prevalence of neovascular AMD and DME has increased substantially over the recent years. Vascular endothelial growth factor (VEGF) has been implicated as playing an important role in the pathogenesis of both neovascular AMD and DME. Since its introduction in 2006, ranibizumab, a recombinant, humanized, monoclonal antibody fragment against all isoforms of VEGF-A, has revolutionized the treatment of neovascular AMD and DME. The efficacy and safety of ranibizumab in neovascular AMD has been demonstrated in the ANCHOR and MARINA trials. Further studies including the PIER, PrONTO, and SUSTAIN trials have also evaluated the optimal dosing regimen of ranibizumab in neovascular AMD. The CATT and IVAN trials compared the safety and efficacy of ranibizumab with off-label use of bevacizumab. Studies such as SUSTAIN and HORIZON have shown that ranibizumab has a good safety profile and is well tolerated for over 4 years with very few serious ocular and systemic adverse events. For DME, Phase II RESOLVE study and Phase III RISE and RIDE studies have demonstrated superiority of ranibizumab treatment in improving vision over placebo controls. Phase II READ and Phase III RESOLVE and REVEAL studies have shown that ranibizumab is more effective both as monotherapy and in combination with laser compared with laser monotherapy. The 3-year results from the DRCRnet protocol I study found that ranibizumab with deferred laser resulted in better long-term visual outcome compared with ranibizumab with prompt laser. This review summarizes various important clinical trials on the long-term efficacy and safety of ranibizumab in the treatment of neovascular AMD and DME. The pharmacological properties of ranibizumab, its cost effectiveness, and impact on quality of life will also be discussed.

  7. Diminishing risk for age related macular degeneration with nutrition: A current view

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly. Clinical hallmarks of AMD are observed in one third of the elderly in industrialized countries. Preventative interventions through dietary modification are attractive strategies because they are more affordable...

  8. Significance of Kampo, Japanese traditional medicine, in the treatment of obesity: basic and clinical evidence.

    PubMed

    Yamakawa, Jun-Ichi; Moriya, Junji; Takeuchi, Kenji; Nakatou, Mio; Motoo, Yoshiharu; Kobayashi, Junji

    2013-01-01

    The cause of obesity includes genetic and environmental factors, including cytokines derived from adipocytes (adipo-cytokines). Although drug therapy is available for obesity, it is highly risky. Our main focus in this review is on the traditional form of Japanese medicine, Kampo, in the treated of obesity. Two Kampo formulas, that is, bofutsushosan () and boiogito (), are covered by the national health insurance in Japan for the treatment of obesity. Various issues related to their action mechanisms remain unsolved. Considering these, we described the results of basic experiments and presented clinical evidence and case reports on osteoarthritis as examples of clinical application of their two Kampo medicine. Traditional medicine is used not only for treatment but also for prevention. In clinical practice, it is of great importance to prove the efficacy of combinations of traditional medicine and Western medicine and the utility of traditional medicine in the attenuation of adverse effects of Western medicine.

  9. Randomization in clinical trials in orthodontics: its significance in research design and methods to achieve it.

    PubMed

    Pandis, Nikolaos; Polychronopoulou, Argy; Eliades, Theodore

    2011-12-01

    Randomization is a key step in reducing selection bias during the treatment allocation phase in randomized clinical trials. The process of randomization follows specific steps, which include generation of the randomization list, allocation concealment, and implementation of randomization. The phenomenon in the dental and orthodontic literature of characterizing treatment allocation as random is frequent; however, often the randomization procedures followed are not appropriate. Randomization methods assign, at random, treatment to the trial arms without foreknowledge of allocation by either the participants or the investigators thus reducing selection bias. Randomization entails generation of random allocation, allocation concealment, and the actual methodology of implementing treatment allocation randomly and unpredictably. Most popular randomization methods include some form of restricted and/or stratified randomization. This article introduces the reasons, which make randomization an integral part of solid clinical trial methodology, and presents the main randomization schemes applicable to clinical trials in orthodontics.

  10. Progress in Metabolomics Standardisation and its Significance in Future Clinical Laboratory Medicine

    PubMed Central

    Koal, Therese

    2016-01-01

    Today, the technology of ‘targeted’ based metabolomics is pivotal in the clinical analysis workflow as it provides information of metabolic phenotyping (metabotypes) by enhancing our understanding of metabolism of complex diseases, biomarker discovery for disease development, progression, treatment, and drug function and assessment. This review is focused on surveying and providing a gap analysis on metabolic phenotyping with a focus on targeted based metabolomics from an instrumental, technical point-of-view discussing the state-of-the-art instrumentation, pre- to post- analytical aspects as well as an overall future necessity for biomarker discovery and future (pre-) clinical routine application. PMID:28149265

  11. Face-to-Face vs. Real-Time Clinical Education: No Significant Difference

    ERIC Educational Resources Information Center

    Mohammed, Y. Q.; Waddington, G.; Donnan, P.

    2007-01-01

    The main objective of this pilot research project was to determine whether the use of an internet broadband link to stream physiotherapy clinical education workshop proceedings in "real-time" is of equivalent educational value to the traditional face-to-face experience. This project looked at the benefits of using the above technology as…

  12. Statistical, Practical, Clinical, and Personal Significance: Definitions and Applications in Speech-Language Pathology

    ERIC Educational Resources Information Center

    Bothe, Anne K.; Richardson, Jessica D.

    2011-01-01

    Purpose: To discuss constructs and methods related to assessing the magnitude and the meaning of clinical outcomes, with a focus on applications in speech-language pathology. Method: Professionals in medicine, allied health, psychology, education, and many other fields have long been concerned with issues referred to variously as practical…

  13. Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer.

    PubMed

    Wilczynski, Milosz; Danielska, Justyna; Dzieniecka, Monika; Szymanska, Bozena; Wojciechowski, Michal; Malinowski, Andrzej

    2016-01-01

    Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients' clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker.

  14. Prognostic and Clinical Significance of miRNA-205 in Endometrioid Endometrial Cancer

    PubMed Central

    Wilczynski, Milosz; Wojciechowski, Michal; Malinowski, Andrzej

    2016-01-01

    Endometrial cancer is one of the most common malignancies of the reproductive female tract, with endometrioid endometrial cancer being the most frequent type. Despite the relatively favourable prognosis in cases of endometrial cancer, there is a necessity to evaluate clinical and prognostic utility of new molecular markers. MiRNAs are small, non-coding RNA molecules that take part in RNA silencing and post-transcriptional regulation of gene expression. Altered expression of miRNAs may be associated with cancer initiation, progression and metastatic capabilities. MiRNA-205 seems to be one of the key regulators of gene expression in endometrial cancer. In this study, we investigated clinical and prognostic role of miRNA-205 in endometrioid endometrial cancer. After total RNA extraction from 100 archival formalin-fixed paraffin-embedded tissues, real-time quantitative RT-PCR was used to define miRNA-205 expression levels. The aim of the study was to evaluate miRNA-205 expression levels in regard to patients’ clinical and histopathological features, such as: survival rate, recurrence rate, staging, myometrial invasion, grading and lymph nodes involvement. Higher levels of miRNA-205 expression were observed in tumours with less than half of myometrial invasion and non-advanced cancers. Kaplan-Maier analysis revealed that higher levels of miRNA-205 were associated with better overall survival (p = 0,034). These results indicate potential clinical utility of miRNA-205 as a prognostic marker. PMID:27737015

  15. Antibiotic use in acne vulgaris and rosacea: clinical considerations and resistance issues of significance to dermatologists.

    PubMed

    Del Rosso, James Q; Leyden, James J; Thiboutot, Diane; Webster, Guy F

    2008-08-01

    Antibiotics are commonly prescribed in dermatology practice for a variety of disorders, including acne vulgaris and rosacea. Importantly, they often are used long-term for these inflammatory dermatoses. Changes in bacterial ecology related to antibiotic prescribing have led to the decreased sensitivity of some bacterial organisms, such as Propionibacterium acnes, to antibiotics commonly prescribed by dermatologists. The potential clinical outcomes of altered bacterial sensitivities may vary among specific disease states and include decreased therapeutic response and the need to alter approaches in disease management. Additionally, changing patterns of antibiotic sensitivity and the emergence of more virulent pathogens, such as community-acquired methicillin-resistant Staphylococcus aureus, macrolide-resistant staphylococci and streptococci, and mupirocin-resistant S aureus, have led to marked changes in how clinicians use antibiotics in clinical practice. This article reviews antibiotic prescribing in dermatology practice and provides important clinical perspectives and recommendations to preserve the therapeutic value of antibiotics based on a thorough review of current literature and clinical experience.

  16. Significant roadblocks exist in developing sputum sample libraries for clinical validation of novel in vitro diagnostics

    PubMed Central

    Dollow, Joshua M; Green, Justin A

    2014-01-01

    With the continuing rise of multiresistant pathogens, reliable, cost-effective, and novel diagnostics are urgently required by clinicians and clinical trialists to diagnose conditions such as respiratory tract infections to enable rational antimicrobial choice and enhance clinical outcomes. However, during product development, validation of these in vitro diagnostic devices, a key regulatory hurdle, requires sputum samples in large numbers. The Rapid Point-of-Care test Platform for Infectious Diseases (RAPP-ID) consortium is tasked with producing point of care test (POCT) platforms for rapid diagnosis of lower respiratory tract infections, including tuberculosis and blood stream infections. Validation of diagnostic platforms would ideally use well-characterized samples in a sputum library taken from a range of clinical settings to allow for a wide panel of pathogens to be assessed. These samples would be stored in specific stable conditions (monitored temperature, specific medium) until required for validation. Therefore we reviewed the current literature for details of storage conditions of sputum samples and for previous validation studies of other diagnostic tests using this methodology. However, we conclude that little data exists, and thus the acquisition and successful storage of good quality clinical samples are major roadblocks in the validation of novel POCT platforms, and that while not without limitations, spiked sputum samples appear the best solution until sputum library laboratory techniques allowing careful preservation of pathogens are improved. PMID:24489460

  17. The geyser sign and torn rotator cuff: clinical significance and pathomechanics.

    PubMed

    Craig, E V

    1984-12-01

    The geyser radiographic sign on shoulder arthrogram is characterized by leakage of dye from the glenohumeral joint into the subdeltoid bursa. The dye outlines the acromioclavicular joint. It is usually an indication of a full-thickness cuff tear of long duration. The clinical occurrence and pathomechanics of this finding indicate that repair is generally difficult.

  18. The antiplatelet effects of nitrates: is it of clinical significance in patients with cardiovascular disease?

    PubMed

    Zhou, Rui-Hai; Frishman, William H

    2010-01-01

    Organic nitrates have been used for over a century in cardiovascular therapy and are still widely used in the treatment of acute coronary syndromes, chronic angina pectoris, and congestive heart failure. Nitrates, together with sodium nitroprusside, generally referred to as nitrovasodilators, exert their biologic effects via the release of nitric oxide. They are also known as nitric oxide donors. The mechanism of action of these drugs is traditionally believed to lie in their arterial vasodilation and venodilation effects, resulting in an improvement of coronary artery blood supply and/or reduction of cardiac workload in the treatment of coronary artery disease and congestive heart failure. Recently it has been recognized that these drugs also have intrinsic antiplatelet and antithrombotic effects, demonstrated both in vitro and in vivo, which would add further rationale for the use of these drugs in atherothrombotic diseases. Research has shown that nitrovasodilators can nonselectively inhibit platelet aggregation induced by multiple stimuli. However, clinical trials have yielded conflicting results regarding clinical outcome, especially with long-term nitrate use. The potentially beneficial effects of nitrates could be negated by the development of tolerance and the generation of deleterious oxidative stress causing endothelial dysfunction during continuous nitrate administration. Much progress has been made in the development of new nitric oxide donors devoid of oxidant-generating properties. Novel combination therapies with nitrovasodilators plus antioxidants or agents with antioxidant properties have shown promise in reducing or reversing tolerance, potentiating antiplatelet effects, and improving clinical outcome. It is expected that clinical introduction of novel nitrovasodilator regimens will provide a new approach to the prevention and treatment of atherothrombotic diseases. Large-scale clinical trials will ultimately provide the evidence-based answers.

  19. New Computer Simulations of Macular Neural Functioning

    NASA Technical Reports Server (NTRS)

    Ross, Muriel D.; Doshay, D.; Linton, S.; Parnas, B.; Montgomery, K.; Chimento, T.

    1994-01-01

    We use high performance graphics workstations and supercomputers to study the functional significance of the three-dimensional (3-D) organization of gravity sensors. These sensors have a prototypic architecture foreshadowing more complex systems. Scaled-down simulations run on a Silicon Graphics workstation and scaled-up, 3-D versions run on a Cray Y-MP supercomputer. A semi-automated method of reconstruction of neural tissue from serial sections studied in a transmission electron microscope has been developed to eliminate tedious conventional photography. The reconstructions use a mesh as a step in generating a neural surface for visualization. Two meshes are required to model calyx surfaces. The meshes are connected and the resulting prisms represent the cytoplasm and the bounding membranes. A finite volume analysis method is employed to simulate voltage changes along the calyx in response to synapse activation on the calyx or on calyceal processes. The finite volume method insures that charge is conserved at the calyx-process junction. These and other models indicate that efferent processes act as voltage followers, and that the morphology of some afferent processes affects their functioning. In a final application, morphological information is symbolically represented in three dimensions in a computer. The possible functioning of the connectivities is tested using mathematical interpretations of physiological parameters taken from the literature. Symbolic, 3-D simulations are in progress to probe the functional significance of the connectivities. This research is expected to advance computer-based studies of macular functioning and of synaptic plasticity.

  20. [New perspectives in the approach to diabetic macular edema. Aflibercept therapy].

    PubMed

    Ruiz-Moreno, J M

    2015-03-01

    The VISTA and VIVID trials were conducted to compare the safety and efficacy of two intravitreal injection (IVI) regimens of aflibercept versus macular laser photocoagulation for the treatment of diabetic macular edema (DME). These double-masked, phase III clinical trials randomized (461/402) patients with DME to receive either 2mg aflibercept IVI every 4 weeks (2q4) or 2mg aflibercept IVI every 8 weeks (2q8) after 5 initial monthly doses vs macular laser photocoagularion. The primary efficacy endpoint was the mean change in best corrected visual acuity (BCVA) from baseline to week 52. Secondary efficacy endpoints were the change in central retinal thickness (CRT), the proportion of patients who gained ≥10 amd ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, and the change in the National Eye Institute Visual Function Questionnaire (NEI VFQ-25) in near and distance vision. The mean BCVA gains in the 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (p<0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (p<0.0001) in VIVID. The proportions of patients gaining ≥ 15 letters and the proportion of patients with an improvement of > 2 levels in the severity of diabetic retinopathy was significant in the treatment groups versus the laser group. Mean reductions in CRT in the 2q4 and 2q8 groups vs the laser group were 185.9 and 183.1 versus 73.3 μm (p<0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm (p<0.0001) in VIVID. The incidences of ocular and nonocular adverse events were similar in all groups. In conclusion, IIV aflibercept demonstrated statistically significant superiority in improvement in BCVA and reduction in DME over laser, with similar efficacy in the 2q4 and 2q8 groups in VISTA and VIVID.

  1. Polarization sensitive changes in the human macula associated with normal aging and age-related macular degeneration

    NASA Astrophysics Data System (ADS)

    VanNasdale, Dean Allan, Jr.

    2011-12-01

    The human macula occupies a relatively small, but crucial retinal area, as it is the location responsible for our most acute spatial vision and best color discrimination. Localizing important landmarks in the retina is difficult even in normal eyes where morphological inter-individual variability is high. This becomes even more challenging in the presence of sight-threatening pathology. With respect to the human macula, there remains a significant gap in the understanding of normal structure and function. Even less is known about the pathological mechanisms that occur in sight-threatening diseases including age-related macular degeneration. Because relatively little is known about normal aging changes, it is also difficult to differentiate those changes from changes associated with retinal disease. To better understand normal and pathological changes in the macula, imaging techniques using specific optical signatures are required. Structural features in the macula can be distinguished based on their intrinsic properties using specific light/tissue interactions. Because of the high degree of structural regularity in the macula, polarization sensitive imaging is potentially a useful tool for evaluating the morphology and integrity of the cellular architecture for both normal individuals and those affected by disease. In our investigations, we used polarization sensitive imaging to determining normal landmarks that are important clinically and for research investigations. We found that precision and accuracy in localizing the central macula was greatly improved through the use of polarization sensitive imaging. We also found that specific polarization alterations can be used to demonstrate systematic changes as a function of age, disproportionately affecting the central macular region. When evaluating patients with age-related macular degeneration, we found that precision and accuracy of localizing the central macula was also improved, even when significant pathology

  2. Clinical Significance of Langerhans Cells in Squamous Cell Carcinoma of the Larynx

    PubMed Central

    Esteban, Francisco; Ruiz-Cabello, Francisco; Gonzalez-Moles, Miguel Angel; Lopez-Gonzalez, Miguel Angel; Funez, Rafael; Redondo, Maximino

    2012-01-01

    Langerhans cells (LCs) may be involved in the immunosurveillance against tumors as antigen-presenting cells. Our objective has been to determine the relevance of LC in progression of larynx squamous cell carcinomas and their relationship with different subpopulations of tumor-infiltrating cells. LCs were investigated by immunohistochemical methods using anti-CD1 antibody. LCs were detected in most of the primary tumors studied (44 out of 50) and also in metastases (6 out of 10) and recurrences (2 out of 3), but we did not find any statistical association between number of LCs and clinical-pathological parameters or survival. However, the number of LCs was increased in patients with evident infiltration of lymphocytes, mainly cytotoxic T cells. We can conclude that although LCs did not show clinical utility as prognostic marker, they may play a role in releasing an active immune response in larynx carcinomas, according to their ability to present antigens to sensitized T cells. PMID:22481933

  3. Digit Symbol-Incidental Learning in the WAIS-III: construct validity and clinical significance.

    PubMed

    Joy, Stephen; Kaplan, Edith; Fein, Deborah

    2003-05-01

    We analyzed WAIS-III/WMS-III standardization data for evidence of the construct validity and clinical utility of the Digit Symbol-Incidental Learning procedures (Pairing and Free Recall). Scores on both tests correlated moderately with WMS-III memory index scores (mean r=.38 for Pairing and .36 for Free Recall). Cutoff scores can be used to identify younger and older adults likely to suffer from memory impairment. In the standardization sample (which excludes neurological patients), these have moderate positive predictive power (averaging .56 if either test yields a positive finding), moderate negative predictive power (.76), and high specificity (.88), but low sensitivity (.35). In a clinical sample, the same cutoff scores were much more sensitive, correctly identifying 88% of a group of patients with Alzheimer's Disease. Examinees who obtain these low scores should receive follow-up memory testing. Very high scores are associated with a reduced risk of memory impairment.

  4. Current perspectives on the epidemiology and pathogenesis of clinically significant Vibrio spp.

    PubMed Central

    Janda, J M; Powers, C; Bryant, R G; Abbott, S L

    1988-01-01

    Recent taxonomic advances have now implicated several different Vibrio species as human pathogens. While the most common clinical presentation of Vibrio infection continues to be gastroenteritis, an increasing number of extraintestinal infections are being reported, particularly in immunocompromised individuals. Detection of Vibrio infections requires a good clinical history and the use of appropriate isolation and identification procedures by the laboratory to confirm illnesses attributed to Vibrio species. Except for Vibrio cholerae O1 and Vibrio parahaemolyticus, there is little direct evidence linking the production of a myriad of cell-associated or extracellular factors produced by each species with human disease and pathogenesis. Many questions regarding pathogenic Vibrio species remain unanswered, including their frequency and distribution in environmental specimens (water, shellfish), infective doses, virulence potential of individual isolates, and markers associated with such strains. Images PMID:3058295

  5. Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

    PubMed Central

    Becker, Karsten; Löffler, Bettina

    2016-01-01

    SUMMARY Sma