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Sample records for clinically significant macular

  1. [Clarifying some concepts and clinical significance of refractory or recurrent neovascular age-related macular degeneration].

    PubMed

    Zhao, Jingke; Sun, Xiaodong

    2015-11-01

    Anti-VEGF therapy is currently one of the main treatments for neovascular age-related macular degeneration (nAMD). Clinically, patients under standardized anti-VEGF therapy showed different responses, of which recurrences or even insensitivity were found in some patients. However, the specific definitions of these various clinical responses are still unclarified. Therefore, to consolidate and define these concepts are of great importance regarding to future efficacy comparison, treatment response clarification and novel drug switching therapies. PMID:26850580

  2. Updates on the Clinical Trials in Diabetic Macular Edema

    PubMed Central

    Demirel, Sibel; Argo, Colby; Agarwal, Aniruddha; Parriott, Jacob; Sepah, Yasir Jamal; Do, Diana V.; Nguyen, Quan Dong

    2016-01-01

    In this era of evidence-based medicine, significant progress has been made in the field of pharmacotherapeutics for the management of diabetic macular edema (DME). A. number of landmark clinical trials have provided strong evidence of the safety and efficacy of agents such as anti-vascular endothelial growth factors for the treatment of DME. Decades of clinical research, ranging from the early treatment of diabetic retinopathy study to the present-day randomized clinical trials (RCTs) testing novel agents, have shifted the goal of therapy from preventing vision loss to ensuring a maximum visual gain. Systematic study designs have provided robust data with an attempt to optimize the treatment regimens including the choice of the agent and timing of therapy. However, due to a number of challenges in the management of DME with approved agents, further studies are needed. For the purpose of this review, an extensive database search in English language was performed to identify prospective, RCTs testing pharmacological agents for DME. In order to acquaint the reader with the most relevant data from these clinical trials, this review focuses on pharmacological agents that are currently approved or have widespread applications in the management of DME. An update on clinical trials presently underway for DME has also been provided. PMID:26957834

  3. The clinical utility of aflibercept for diabetic macular edema

    PubMed Central

    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. PMID:26425104

  4. Cental Macular Thickness in Patients with Type 2 Diabetes Mellitus without Clinical Retinopathy.

    PubMed

    Demir, Mehmet; Dirim, Burcu; Acar, Zeynep; Yılmaz, Murat; Sendul, Yekta

    2013-01-01

    Objective. To compare central macular thickness (CMT) of diabetic patients with type 2 diabetes without clinical retinopathy and healthy subjects. Materials and Methods. Optical coherence tomography (OCT) measurements were performed in 124 eyes of 62 subjects with diabetes mellitus without clinical retinopathy (study group: 39 females, 23 males; mean age: 55.06 ± 9.77 years) and in 120 eyes of 60 healthy subjects (control group: 35 females, 25 males; mean age: 55.78 ± 10.34 years). Blood biochemistry parameters were analyzed in all cases. The data for central macular thickness (at 1 mm), the levels of fasting plasma glucose, and glycosylated hemoglobin (HbA1c) were compared in both groups. Results. The mean central macular thickness was 232.12 ± 24.41 µm in the study group and 227.19 ± 29.94 µm in the control group. The mean HbA1c level was 8.92 ± 2.58% in the study group and 5.07 ± 0.70% in the control group (P = 0.001). No statistically significant relationship was found between CMT, HbA1c, and fasting plasma glucose level in either group (P > 0.05). Conclusions. Central macular thickness was not significantly thicker in patients with type 2 diabetes without clinical retinopathy than in healthy subjects. PMID:23691279

  5. 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

  6. Multimodality imaging in clinical diagnosis and treatment of macular disease

    NASA Astrophysics Data System (ADS)

    Taibl, Jessica N.; Sayegh, Samir I.

    2013-03-01

    Accurate diagnosis and treatment of disease is a function of how well the pathology can be imaged. Coregistering images from different modalities can offer significant advantages. Multi-modal imaging is finding its place in Ophthalmology and we illustrate and analyze its use in macular disease. New technologies have provided the ability to simultaneously capture FA and OCT images, allowing dynamic analysis at the exact point of interest. We establish that the combined imaging protocol is easier and faster for both patient and technician, and ultimately and most importantly more capable of guiding the physician to a diagnosis and treatment.

  7. Macular amyloidosis complicating macroprolactinoma--a novel clinical association.

    PubMed

    Dutta, Deep; Ahuja, Arvind; Sharma, Lokesh; Bhardwaj, Minakshi; Kulshreshtha, Bindu

    2015-01-01

    Amyloid deposition in the pituitary gland is a rare localised form of amyloidosis, and most commonly reported with prolactinoma. Macular amyloidosis is a rare form of localised cutaneous amyloidosis of obscure aetiology. In contrast to most localised amyloidosis, the precursor protein(s) of both macular amyloidosis and prolactinoma are unknown. A 35-year-old man with chronic headache (six years), blurring of vision (three years), and hyperpigmented macular lesion involving arms, legs, and back (two years) was diagnosed to have hyperprolactinaemia (8927 ng/mL) and secondary adrenal insufficiency. MRI revealed pituitary macroadenoma compressing the optic chiasma, encasing the right carotid artery and extending into the sphenoid sinus. A biopsy of skin from the right upper arm revealed thickened stratum corneum, acanthosis, and deposition of pale eosinophilic material in papillary dermis that gave a rose pink colour under methyl-violet and appeared congophilic with Congo red stain, which under polarised light showed green birefringence, diagnostic of macular amyloidosis. Headache, bitemporal haemianopia, and skin lesion improved following cabergoline therapy. Temporal profile of the disease characterised by symptoms of macroprolactinoma preceding onset of macular amyloidosis with resolution of symptoms of macroprolactinoma, accompanied by reductions in prolactin, and concomitant improvement in macular amyloidosis with cabergoline therapy may suggest some link between macroprolactinoma and macular amyloidosis. This report intends to highlight this novel association of macular amyloidosis and macroprolactinoma. PMID:26662655

  8. Role of aflibercept for macular edema following branch retinal vein occlusion: comparison of clinical trials

    PubMed Central

    Oellers, Patrick; Grewal, Dilraj S; Fekrat, Sharon

    2016-01-01

    For years, the standard of care for branch-retinal-vein-occlusion-associated macular edema was initial observation followed by grid-pattern laser photocoagulation for persistent edema. Newer pharmacologic options have revolutionized the management of branch-retinal-vein-occlusion-associated macular edema, and the visual outcomes of these eyes are better than ever. However, a variety of available treatment options including intravitreal corticosteroids and intravitreal anti-vascular endothelial growth factor agents have established novel challenges with regard to appropriate drug selection. This review summarizes the available clinical studies with special emphasis on the comparison of intravitreal aflibercept with ranibizumab, bevacizumab, and steroid agents. PMID:27022238

  9. Clinical applications of the sustained-release dexamethasone implant for treatment of macular edema

    PubMed Central

    Herrero-Vanrell, Rocío; Cardillo, Jose Augusto; Kuppermann, Baruch D

    2011-01-01

    Macular edema is one of the leading causes of vision loss among patients with retinal vein occlusion, diabetic retinopathy, and posterior chamber inflammatory disease. However, the treatment of macular edema is considerably limited by the difficulty in delivering effective doses of therapeutic agents into the vitreous cavity. In recent years, the development of a sustained-release dexamethasone intravitreal implant (Ozurdex®) has enabled more controlled drug release at a stable rate over a long period of time, with a potentially lower rate of adverse events. Clinical studies indicate that this dexamethasone implant is a promising new treatment option for patients with persistent macular edema resulting from retinal vein occlusion, diabetic retinopathy, and uveitis or Irvine-Gass syndrome. PMID:21383939

  10. "Clinical" Significance: "Clinical" Significance and "Practical" Significance are NOT the Same Things

    ERIC Educational Resources Information Center

    Peterson, Lisa S.

    2008-01-01

    Clinical significance is an important concept in research, particularly in education and the social sciences. The present article first compares clinical significance to other measures of "significance" in statistics. The major methods used to determine clinical significance are explained and the strengths and weaknesses of clinical significance…

  11. Clinical trials on corticosteroids for diabetic macular edema

    PubMed Central

    Al Dhibi, Hassan A; Arevalo, J Fernando

    2013-01-01

    Diabetic macular edema (DME) is a common cause of visual impairment in diabetic patients. It is caused by an increase in the permeability of the perifoveal capillaries and a disruption of the blood retinal-barrier. The pathogenesis of DME is multifactorial. Several therapeutic modalities have been proposed for the treatment of DME. Corticosteroid treatments have emerged as an alternative therapy for persistent DME or refractory to conventional laser photocoagulation and other modalities, due to anti-inflammatory, anti-vascular endothelial growth factor and anti-proliferative effects. Many studies have demonstrated the beneficial therapeutic effect of corticosteroids with improvement to both retinal thickness and visual acuity in short-term on the treatment of DME. Peribulbar and intravitreal injections have been used to deliver steroids for DME with frequent injections due to the chronic and recurrent nature of the disease. Steroid-related side effects include elevated intraocular pressure, cataract, and injection related complications such as endophthalmitis, vitreous hemorrhage, and retinal detachment particularly with intravitreal steroid injections. In order to reduce the risks, complications and frequent dosing of intravitreal steroids, intravitreal implants have been developed recently to provide sustained release of corticosteroids and reduce repeated intravitreal injections for the management of DME. PMID:24379920

  12. 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

  13. Clinical effect of intravitreous injection of triamcinolone acetonide in treating cystoid macular edema.

    PubMed

    Yan, P S; Qian, C; Wan, G M; Wang, W Z; Dong, Y; Li, F Z

    2016-01-01

    Cystoid macular edema (CME), a commonly seen sign for multiple fundus diseases, is able to induce visual deterioration. The incidence rate of CME is constantly increasing; however, the existing clinical treatments cannot achieve satisfactory curative effects. To explore the curative effect of intravitreous injection of triamcinolone acetonide (TA) in treating CME, this study carried out a clinical test on 39 patients (42 eyes) from The First Affiliated Hospital of Zhengzhou University who developed CME induced by central retinal vein occlusion (CRVO). All 42 eyes received intravitreous injection of 40 mg/ml TA (0.1 ml) and then were followed up for 11-23.5 months. Eyes were examined by slit-lamp microscope, fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) and best corrected visual acuity (BCVA), and intraocular pressure (IOP) of those eyes were detected before and after treatment. Average vision of eyes was 0.1 before treatment, and the vision improved in one month (vision ≥ 0.2: 100%; vision ≥ 0.5: 42.9%) and three months (vision ≥ 0.2: 64.3%; vision ≥ 0.5: 21.4%) after treatment; but as time went on, the vision of some patients declined; at the last follow-up, patients with vision ≥ 0.2 accounted for 28.6% and those with vision ≥0.5 accounted for 7.1%; compared to before treatment, 71.4% patients had improved vision and the remaining 28.6% had declined vision. Some patients were observed with high IOP during treatment, and 7 eyes were found with secondary cataract in posterior capsule of lens at the last follow-up. Intravitreous injection of triamcinolone acetonide proved to have significant short-term curative effect on CEM which is non-sensitive to conventional therapies, but it is likely to induce high IPO and posterior capsular opacification. PMID:27049093

  14. 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

  15. 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

  16. 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

  17. Clinical significance of complement deficiencies.

    PubMed

    Pettigrew, H David; Teuber, Suzanne S; Gershwin, M Eric

    2009-09-01

    The complement system is composed of more than 30 serum and membrane-bound proteins, all of which are needed for normal function of complement in innate and adaptive immunity. Historically, deficiencies within the complement system have been suspected when young children have had recurrent and difficult-to-control infections. As our understanding of the complement system has increased, many other diseases have been attributed to deficiencies within the complement system. Generally, complement deficiencies within the classical pathway lead to increased susceptibility to encapsulated bacterial infections as well as a syndrome resembling systemic lupus erythematosus. Complement deficiencies within the mannose-binding lectin pathway generally lead to increased bacterial infections, and deficiencies within the alternative pathway usually lead to an increased frequency of Neisseria infections. However, factor H deficiency can lead to membranoproliferative glomerulonephritis and hemolytic uremic syndrome. Finally, deficiencies within the terminal complement pathway lead to an increased incidence of Neisseria infections. Two other notable complement-associated deficiencies are complement receptor 3 and 4 deficiency, which result from a deficiency of CD18, a disease known as leukocyte adhesion deficiency type 1, and CD59 deficiency, which causes paroxysmal nocturnal hemoglobinuria. Most inherited deficiencies of the complement system are autosomal recessive, but properidin deficiency is X-linked recessive, deficiency of C1 inhibitor is autosomal dominant, and mannose-binding lectin and factor I deficiencies are autosomal co-dominant. The diversity of clinical manifestations of complement deficiencies reflects the complexity of the complement system. PMID:19758139

  18. Macular telangiectasia type 2.

    PubMed

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

    2013-05-01

    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 non-neovascular 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 function

  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. Clinical significance of adaptive thermogenesis.

    PubMed

    Major, G C; Doucet, E; Trayhurn, P; Astrup, A; Tremblay, A

    2007-02-01

    The epidemic of obesity is developing faster than the scientific understanding of an efficient way to overcome it, as reflected by the low success rate of short- and long-term weight loss interventions. From a clinical standpoint, this suggests that the body tends to defend a set point of possible genetic origin in the context of a weight-reducing program. As described in this paper, this limited therapeutic success may depend on adaptive thermogenesis, which represents in this case the decrease in energy expenditure (EE) beyond what could be predicted from the changes in fat mass or fat-free mass under conditions of standardized physical activity in response to a decrease in energy intake. This issue has been documented in recent studies that have shown in obese individuals adhering to a weight reduction program a greater than predicted decrease in EE, which in some cases was quantitatively sufficient to overcome the prescribed energy restriction, suggesting a role for adaptive thermogenesis in unsuccessful weight loss interventions and reduced body weight maintenance. As also discussed in this paper, this 'adaptive thermogenesis' can be influenced by environmental factors, which have not been frequently considered up to now. This is potentially the case for plasma organochlorine concentration and oxygen desaturation in obstructive sleep apnea syndrome. It is concluded that health professionals should be aware that in some vulnerable individuals, adaptive thermogenesis can be multi-causal, and has the capacity to compensate, at least partly, for the prescribed energy deficit, possibly going beyond any good compliance of some patients. PMID:17260010

  1. 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)

  2. Randomised clinical trial evaluating best-corrected visual acuity and central macular thickness after 532-nm subthreshold laser grid photocoagulation treatment in diabetic macular oedema

    PubMed Central

    Pei-pei, W; Shi-zhou, H; Zhen, T; Lin, L; Ying, L; Jiexiong, O; Wen-bo, Z; Chen-jin, J

    2015-01-01

    Purpose To compare best-corrected visual acuity (BCVA) and central macular thickness (CMT) after 532-nm subthreshold laser grid photocoagulation and threshold laser grid photocoagulation for the treatment of diabetic macular oedema (DME). Patients and methods Twenty-three patients (46 eyes) with binocular DME were enroled in this study. The two eyes of each patient were divided into a subthreshold photocoagulation group and a threshold photocoagulation group. The eyes of the subthreshold group underwent 532-nm patter scan laser system (PASCAL) 50% end point subthreshold laser grid photocoagulation therapy, whereas the threshold photocoagulation group underwent short-pulse grid photocoagulation with a 532-nm PASCAL system. BCVA and CMT were assessed in all patients before treatment, 7 days after treatment, and 1, 3, and 6 months after treatment. Results After grid photocoagulation, the mean BCVA improved in both the subthreshold group, and the threshold group, and the two groups did not differ statistically significantly from each other. Similarly, the macular oedema diminished in both groups after treatment, and the two groups did not differ statistically significantly from each other with regard to CMT. Conclusion Both 532-nm subthreshold laser grid photocoagulation and threshold laser grid photocoagulation can improve the visual acuity and reduce CMT in DME patients. PMID:25697457

  3. Clinical significance of monocyte heterogeneity.

    PubMed

    Stansfield, Brian K; Ingram, David A

    2015-01-01

    Monocytes are primitive hematopoietic cells that primarily arise from the bone marrow, circulate in the peripheral blood and give rise to differentiated macrophages. Over the past two decades, considerable attention to monocyte diversity and macrophage polarization has provided contextual clues into the role of myelomonocytic derivatives in human disease. Until recently, human monocytes were subdivided based on expression of the surface marker CD16. "Classical" monocytes express surface markers denoted as CD14(++)CD16(-) and account for greater than 70% of total monocyte count, while "non-classical" monocytes express the CD16 antigen with low CD14 expression (CD14(+)CD16(++)). However, recognition of an intermediate population identified as CD14(++)CD16(+) supports the new paradigm that monocytes are a true heterogeneous population and careful identification of specific subpopulations is necessary for understanding monocyte function in human disease. Comparative studies of monocytes in mice have yielded more dichotomous results based on expression of the Ly6C antigen. In this review, we will discuss the use of monocyte subpopulations as biomarkers of human disease and summarize correlative studies in mice that may yield significant insight into the contribution of each subset to disease pathogenesis. PMID:25852821

  4. Macular Diplopia.

    PubMed

    Shippman, Sara; Cohen, Kenneth R; Heiser, Larissa

    2015-01-01

    Maculopathies affect point-to-point foveal correspondence causing diplopia. The effect that the maculopathies have on the interaction of central sensory fusion and peripheral fusion are different than the usual understanding of treatment for diplopia. This paper reviews the pathophysiology of macular diplopia, describes the binocular pathology causing the diplopia, discusses the clinical evaluation, and reviews the present treatments including some newer treatment techniques. PMID:26564922

  5. Krypton laser photocoagulation for neovascular lesions of age-related macular degeneration. Results of a randomized clinical trial. Macular Photocoagulation Study Group.

    PubMed

    1990-06-01

    The Age-Related Macular Degeneration Study-Krypton Laser (AMDS-K) is a multicenter controlled clinical trial designed to determine whether krypton red laser photocoagulation is of value in preventing visual acuity loss in eyes with macular degeneration that have either choroidal neovascularization 1 to 199 microns from the center of the foveal avascular zone or choroidal neovascularization 200 microns or farther from the foveal avascular zone center with blood and/or blocked fluorescence extending within 200 microns of the foveal avascular zone center. Recruitment ended in December 1987 after 247 patients had been assigned to photocoagulation and 249 patients had been assigned to no treatment. At 3 years after randomization, 49% (86/174) of treated eyes, in contrast to 58% (98/169) of untreated eyes, had lost six or more lines of visual acuity. The average visual acuity of treated and untreated eyes at that time was 20/200 and 20/250, respectively. The benefit of laser treatment was largest among patients without evidence of hypertension and diminished to no apparent benefit among patients who had highly elevated blood pressure and/or used antihypertensive medication. Treatment of lesions meeting the AMDS-K eligibility criteria in eyes of patients with no hypertension is recommended. However, treatment cannot be recommended uniformly for patients with definite hypertension having lesions similar to those of patients enrolled in the AMDS-K. PMID:1693496

  6. 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

  7. 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. PMID:26957835

  8. Functional and clinical data of Best vitelliform macular dystrophy patients with mutations in the BEST1 gene

    PubMed Central

    Zerbib, Jennyfer; Santacroce, Rossana; Margaglione, Maurizio; Delphin, Nathalie; Rozet, Jean-Michel; Kaplan, Josseline; Martinelli, Domenico; Delle Noci, Nicola; Soubrane, Gisèle; Souied, Eric H.

    2009-01-01

    Purpose To analyze functional and clinical data of Best vitelliform macular dystrophy (VMD) patients with mutations in the BEST1 gene. Methods Best VMD patients with BEST1 mutations were evaluated prospectively regarding age, age of onset, best-corrected visual acuity (BCVA), fundus autofluorescence, fluorescein angiography, optical coherence tomography, and electro-oculography. Mutations in BEST1 were established by direct sequencing. Results Forty-six eyes of 23 patients (10 male, 13 female) were included in the study. We identified nine different BEST1 mutations (3/9 novel), in ten unrelated families. The age of patients ranged between 3 and 75 years; age of onset varied between 2 and 67 years. BCVA ranged between 20/20 and 20/200. On the basis of fundus biomicroscopy with direct illumination, using one widely accepted classification, the macular lesions could be counted as follows: 1. no lesion (normal fovea): eight eyes, five patients carrying a mutation on the BEST1 gene; 2. previtelliform lesions: six eyes, three affected patients; 3. vitelliform lesions: four eyes, two affected patients; 4. pseudohypopyon: three eyes, three affected patients; 5. vitelliruptive lesions (scrambled egg aspect with dispersion of the vitelliform material without sign of atrophy or fibrosis): ten eyes, six affected patients; 6. atrophic lesions (atrophy with or without residual dispersed material): seven eyes, five patients; 7. fibrotic lesions: eight eyes, five patients. Two patients presented unilateral Best VMD. Both eyes of two patients presented multifocal Best VMD features on fundus examination. Six eyes of four patients have been treated for choroidal neovascularization by thermic photocoagulation [one eye], photodynamic therapy [three eyes], and intravitreal ranibizumab injection [two eyes]. Comparison of interfamilial and intrafamilial clinical data between patients did not reveal differences in age, BCVA, and stage of the disease as evaluated by fundus autofluorescence

  9. Retinal vein occlusion and macular edema – critical evaluation of the clinical value of ranibizumab

    PubMed Central

    Keane, Pearse A; Sadda, Srinivas R

    2011-01-01

    Retinal vein occlusions (RVOs) constitute the second most common cause of retinal vascular disease after diabetic retinopathy, with a prevalence of between 1% and 2% in persons older than 40 years of age. Despite the existence of numerous potential therapeutic options, none is entirely satisfactory, and many patients with RVO suffer irreversible visual loss. Fortunately however, the recent introduction of antivascular endothelial growth factor (VEGF) agents, such as ranibizumab (Lucentis®, Genentech, South San Francisco, CA) and bevacizumab (Avastin®, Genentech), offers a potentially new treatment approach for clinicians managing this disorder. The results of the BRAVO and CRUISE trials have provided the first definitive evidence for the efficacy and safety of ranibizumab in the treatment of RVO. As a result, ranibizumab has recently been approved by the US Food and Drug Administration for the treatment of RVO-associated macular edema. In this review, we provide a critical evaluation of clinical trial data for the safety and efficacy of ranibizumab, and address unresolved issues in the management of this disorder. PMID:21750610

  10. Critical Appraisal of Clinical Practice Guidelines for Age-Related Macular Degeneration

    PubMed Central

    Wu, Annie M.; Wu, Connie M.; Young, Benjamin K.; Wu, Dominic J.; Margo, Curtis E.; Greenberg, Paul B.

    2015-01-01

    Purpose. To evaluate the methodological quality of age-related macular degeneration (AMD) clinical practice guidelines (CPGs). Methods. AMD CPGs published by the American Academy of Ophthalmology (AAO) and Royal College of Ophthalmologists (RCO) were appraised by independent reviewers using the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, which comprises six domains (Scope and Purpose, Stakeholder Involvement, Rigor of Development, Clarity of Presentation, Applicability, and Editorial Independence), and an Overall Assessment score summarizing methodological quality across all domains. Results. Average domain scores ranged from 35% to 83% for the AAO CPG and from 17% to 83% for the RCO CPG. Intraclass correlation coefficients for the reliability of mean scores for the AAO and RCO CPGs were 0.74 and 0.88, respectively. The strongest domains were Scope and Purpose and Clarity of Presentation. The weakest were Stakeholder Involvement (AAO) and Editorial Independence (RCO). Conclusions. Future AMD CPGs can be improved by involving all relevant stakeholders in guideline development, ensuring transparency of guideline development and review methodology, improving guideline applicability with respect to economic considerations, and addressing potential conflict of interests within the development group. PMID:26106484

  11. 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.

  12. 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

  13. 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.

  14. Clinical significance of human papillomavirus genotyping

    PubMed Central

    Choi, Youn Jin

    2016-01-01

    Cervical cancer is the fourth most common cancer in women worldwide, and the human papillomavirus (HPV) is the main causative agent for its development. HPV is a heterogeneous virus, and a persistent infection with a high-risk HPV contributes to the development of cancer. In recent decades, great advances have been made in understanding the molecular biology of HPV, and HPV’s significance in cervical cancer prevention and management has received increased attention. In this review, we discuss the role of HPV genotyping in cervical cancer by addressing: clinically important issues in HPV virology; the current application of HPV genotyping in clinical medicine; and potential future uses for HPV genotyping. PMID:26768784

  15. Differences in the Genetic Susceptibility to Age-Related Macular Degeneration Clinical Subtypes

    PubMed Central

    Shen, Ling; Hoffmann, Thomas J.; Melles, Ronald B.; Sakoda, Lori C.; Kvale, Mark N.; Banda, Yambazi; Schaefer, Catherine; Risch, Neil; Jorgenson, Eric

    2015-01-01

    Purpose We compared across age-related macular degeneration (AMD) subtypes the effect of AMD risk variants, their predictive power, and heritability. Methods The prevalence of AMD was estimated among active non-Hispanic white Kaiser Permanente Northern California members who were at least 65 years of age as of June 2013. The genetic analysis included 5,170 overall AMD cases ascertained from electronic health records (EHR), including 1,239 choroidal neovascularization (CNV) cases and 1,060 nonexudative AMD cases without CNV, and 23,130 controls of non-Hispanic white ancestry from the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Imputation was based on the 1000 Genomes Project reference panel. Results The narrow-sense heritability due to common autosomal single nucleotide polymorphisms (SNPs) was 0.37 for overall AMD, 0.19 for AMD unspecified, 0.20 for nonexudative AMD, and 0.60 for CNV. For the 19 previously reported AMD risk loci, the area under the receiver operating characteristic (ROC) curve was 0.675 for overall AMD, 0.640 for AMD unspecified, 0.678 for nonexudative AMD, and 0.766 for CNV. The individual effects on the risk of AMD for 18 of the 19 SNPs were in a consistent direction with those previously reported, including a protective effect of the APOE ε4 allele. Conversely, the risk of AMD was significantly increased in carriers of the ε2 allele. Conclusions These findings provide an independent confirmation of many of the previously identified AMD risk loci, and support a potentially greater role of genetic factors in the development of CNV. The replication of established associations validates the use of EHR in genetic studies of ophthalmologic traits. PMID:26176866

  16. 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.

  17. Advances in the management of diabetic macular oedema based on evidence from the Diabetic Retinopathy Clinical Research Network

    PubMed Central

    Lim, Lik Thai; Chia, Seen Nee; Ah-kee, Elliott Yann; Chew, Nejia; Gupta, Manish

    2015-01-01

    The Diabetic Retinopathy Clinical Research Network (DRCR.net) performs studies on new treatments for diabetic retinopathy. This review aims to summarise recent findings from DRCR.net studies on the treatment of diabetic macular oedema. We performed a PubMed search of articles from the DRCR.net, which included all studies pertaining to the treatment of diabetic maculopathy. The main outcome measures were retinal thickening as assessed by central subfield thickness on optical coherence tomography and improvement of visual acuity on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Findings from each study were divided into modalities of treatment, namely photocoagulation, bevacizumab, triamcinolone, ranibizumab and vitrectomy. While modified ETDRS focal/grid laser remains the standard of care, intravitreal corticosteroids or anti-vascular endothelial growth factor agents have also proven to be effective, although they come with associated side effects. The choice of treatment modality for diabetic macular oedema is a clinical judgement call, and depends on the patient’s clinical history and assessment. PMID:26034315

  18. 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

  19. The clinical significance of marginal fit.

    PubMed

    Larson, Thomas D

    2012-01-01

    Clinical evaluation of restoration acceptability includes marginal adaptation, restoration and preservation of anatomic form, color match, cavosurface discoloration, and presence of marginal caries. This paper will review what is known about marginal fit of all materials relative to their acceptable fit. Some explanation will be given of how material properties affect marginal fit, what the expected longevity of different materials is relative to marginal fit, and how marginal fit affects development of secondary or marginal caries. Marginal fit is assumed to affect restoration longevity by either encouraging or discouraging microleakage and development of secondary or marginal caries. Marginal fit and its effect on the health of the gingival tissues have been reviewed in an earlier paper on polishing and will not be reviewed here. Is there some correlation between marginal fit of the various materials used in restorative dentistry and this assumption? This paper will review the literature found on Medline and present the science behind the clinical significance of marginal fit utilizing in vitro studies where necessary and in vivo studies whenever possible. Numerous authors replicating these studies are used to improve reliability and replicability. PMID:22439529

  20. 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

  1. Subchorionic hemorrhage: sonographic diagnosis and clinical significance.

    PubMed

    Abu-Yousef, M M; Bleicher, J J; Williamson, R A; Weiner, C P

    1987-10-01

    Twenty-one pregnancies with sonographic evidence of subchorionic hemorrhage were evaluated clinically and sonographically. Clinical evaluation included maternal age, gravidity, parity, gestational age, presence of pain, presence and amount of bleeding, and pregnancy outcome. Sonographic evaluation included the relative and absolute size of the hematoma, its echogenicity and location in relation to the placenta, the presence of marginal placental abruption, and progress on follow-up examinations. The outcome of these pregnancies was unfavorable in 15 cases (71%) and correlated well with the relative and absolute size of the hematoma, severity of vaginal bleeding, change in hematoma size on follow-up examination, and presence of pain. There was no significant correlation between the outcome and the echogenicity of the hematoma, presence of placental margin elevation, gestational and maternal age, gravidity, or parity. All hematomas extended to the margin of the placenta. Subchorionic hemorrhage is a frequent cause of first and second trimester bleeding and has a grave prognosis. Familiarity with the varied sonographic appearances and meticulous sonographic examination with special attention to the placental margins can be helpful in the diagnosis. PMID:3307354

  2. 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

  3. 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. PMID:8869690

  4. The clinical significance of small subarachnoid hemorrhages.

    PubMed

    Albertine, Paul; Borofsky, Samuel; Brown, Derek; Patel, Smita; Lee, Woojin; Caputy, Anthony; Taheri, M Reza

    2016-06-01

    With advancing technology, the sensitivity of computed tomography (CT) for the detection of traumatic subarachnoid hemorrhage (tSAH) continues to improve. Increased resolution has allowed for the detection of hemorrhage that is limited to one or two images of the CT exam. At our institution, all patients with a SAH require intensive care unit (ICU) admission, regardless of size. It was our hypothesis that patients with small subarachnoid hemorrhage experience favorable outcomes, and may not require the intensive monitoring offered in the ICU. This retrospective study evaluated 62 patients between 2011 and 2014 who presented to our Level I trauma center emergency room for acute traumatic injuries, and found to have subarachnoid hemorrhages on CT examination. The grade of subarachnoid hemorrhage was determined using previously utilized scoring systems, such as the Fisher, Modified Fisher, and Claassen grading systems. Electronic medical records were used to evaluate for medical decline, neurological decline, neurosurgical intervention, and overall hospital course. Admitting co-morbidities were noted, as were the presence of patient intoxication and use of anticoagulants. Patient outcomes were based on discharge summaries upon which the neurological status of the patient was assessed. Each patient was given a score based on the Glasgow outcome scale. The clinical and imaging profile of 62 patients with traumatic SAH were studied. Of the 62 patients, 0 % underwent neurosurgical intervention, 6.5 % had calvarial fractures, 25.8 % had additional intracranial hemorrhages, 27.4 % of the patients had significant co-morbidities, and 1.6 % of the patients expired. Patients with low-grade tSAH spent less time in the ICU, demonstrated neurological and medical stability during hospitalization. None of the patients with low-grade SAH experienced seizure during their admission. In our study, patients with low-grade tSAH demonstrated favorable clinical outcomes. This suggests

  5. Myopic Macular Retinoschisis in Teenagers: Clinical Characteristics and Spectral Domain Optical Coherence Tomography Findings.

    PubMed

    Sun, Chuan-Bin; You, Yong-Sheng; Liu, Zhe; Zheng, Lin-Yan; Chen, Pei-Qing; Yao, Ke; Xue, An-Quan

    2016-01-01

    To investigate the morphological characteristics of myopic macular retinoschisis (MRS) in teenagers with high myopia, six male (9 eyes) and 3 female (4 eyes) teenagers with typical MRS identified from chart review were evaluated. All cases underwent complete ophthalmic examinations including best corrected visual acuity (BCVA), indirect ophthalmoscopy, colour fundus photography, B-type ultrasonography, axial length measurement, and spectral-domain optical coherence tomography (SD-OCT). The average age was 17.8 ± 1.5 years, average refractive error was -17.04 ± 3.04D, average BCVA was 0.43 ± 0.61, and average axial length was 30.42 ± 1.71 mm. Myopic macular degenerative changes (MDC) by colour fundus photographs revealed Ohno-Matsui Category 1 in 4 eyes, and Category 2 in 9 eyes. Posterior staphyloma was found in 9 eyes. SD-OCT showed outer MRS in all 13 eyes, internal limiting membrane detachment in 7 eyes, vascular microfolds in 2 eyes, and inner MRS in 1 eye. No premacular structures such as macular epiretinal membrane or partially detached posterior hyaloids were found. Our results showed that MRS rarely occurred in highly myopic teenagers, and was not accompanied by premacular structures, severe MDC, or even obvious posterior staphyloma. This finding indicates that posterior scleral expansion is probably the main cause of MRS. PMID:27294332

  6. Myopic Macular Retinoschisis in Teenagers: Clinical Characteristics and Spectral Domain Optical Coherence Tomography Findings

    PubMed Central

    Sun, Chuan-bin; You, Yong-sheng; Liu, Zhe; Zheng, Lin-yan; Chen, Pei-qing; Yao, Ke; Xue, An-quan

    2016-01-01

    To investigate the morphological characteristics of myopic macular retinoschisis (MRS) in teenagers with high myopia, six male (9 eyes) and 3 female (4 eyes) teenagers with typical MRS identified from chart review were evaluated. All cases underwent complete ophthalmic examinations including best corrected visual acuity (BCVA), indirect ophthalmoscopy, colour fundus photography, B-type ultrasonography, axial length measurement, and spectral-domain optical coherence tomography (SD-OCT). The average age was 17.8 ± 1.5 years, average refractive error was −17.04 ± 3.04D, average BCVA was 0.43 ± 0.61, and average axial length was 30.42 ± 1.71 mm. Myopic macular degenerative changes (MDC) by colour fundus photographs revealed Ohno-Matsui Category 1 in 4 eyes, and Category 2 in 9 eyes. Posterior staphyloma was found in 9 eyes. SD-OCT showed outer MRS in all 13 eyes, internal limiting membrane detachment in 7 eyes, vascular microfolds in 2 eyes, and inner MRS in 1 eye. No premacular structures such as macular epiretinal membrane or partially detached posterior hyaloids were found. Our results showed that MRS rarely occurred in highly myopic teenagers, and was not accompanied by premacular structures, severe MDC, or even obvious posterior staphyloma. This finding indicates that posterior scleral expansion is probably the main cause of MRS. PMID:27294332

  7. 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.

  8. 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

  9. Two novel mutations in the bestrophin-1 gene and associated clinical observations in patients with best vitelliform macular dystrophy

    PubMed Central

    LIN, YING; GAO, HONGBIN; LIU, YUHUA; LIANG, XUANWEI; LIU, XIALIN; WANG, ZHONGHAO; ZHANG, WANJUN; CHEN, JIANGNA; LIN, ZHUOLING; HUANG, XINHUA; LIU, YIZHI

    2015-01-01

    The purpose of the current study was to investigate the 11 bestrophin-1 (BEST1) exons in patients with best vitelliform macular dystrophy (BVMD), and to characterize the associated clinical features. Complete ophthalmic examinations were conducted on two families, and two family members were diagnosed with BVMD. Genomic DNA was extracted from the leukocytes of peripheral blood collected from the patients and their family members, in addition to 100 unrelated control subjects recruited from the same population. The polymerase chain reaction was used to amplify a total of 11 exons of the BEST1 gene, which were directly sequenced. Ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination, fundus examination, fundus photography and fluorescein angiography imaging, as well as anterior segment analysis with Pentacam and optical coherence tomography, were conducted. The patients exhibited yellowish lesions in the macular area. A heterozygous mutation c.910_912delGAT (p.304del Asp) in exon 7 was identified in Case 1. A heterozygous BEST1 missense mutation c.685T>G (p.Trp229Gly) in exon 5 was identified in Case 2, but not in any of the unaffected family members or normal controls. Although BEST1 gene mutations and polymorphisms have previously been reported in various ethnic groups, the current study identified, for the first time to the best of our knowledge, two novel BEST1 gene mutations in patients with BVMD. PMID:25936525

  10. Two novel mutations in the bestrophin-1 gene and associated clinical observations in patients with best vitelliform macular dystrophy.

    PubMed

    Lin, Ying; Gao, Hongbin; Liu, Yuhua; Liang, Xuanwei; Liu, Xialin; Wang, Zhonghao; Zhang, Wanjun; Chen, Jiangna; Lin, Zhuoling; Huang, Xinhua; Liu, Yizhi

    2015-08-01

    The purpose of the current study was to investigate the 11 bestrophin-1 (BEST1) exons in patients with best vitelliform macular dystrophy (BVMD), and to characterize the associated clinical features. Complete ophthalmic examinations were conducted on two families, and two family members were diagnosed with BVMD. Genomic DNA was extracted from the leukocytes of peripheral blood collected from the patients and their family members, in addition to 100 unrelated control subjects recruited from the same population. The polymerase chain reaction was used to amplify a total of 11 exons of the BEST1 gene, which were directly sequenced. Ophthalmic examinations, including best-corrected visual acuity, slit-lamp examination, fundus examination, fundus photography and fluorescein angiography imaging, as well as anterior segment analysis with Pentacam and optical coherence tomography, were conducted. The patients exhibited yellowish lesions in the macular area. A heterozygous mutation c.910_912delGAT (p.304del Asp) in exon 7 was identified in Case 1. A heterozygous BEST1 missense mutation c.685T>G (p.Trp229Gly) in exon 5 was identified in Case 2, but not in any of the unaffected family members or normal controls. Although BEST1 gene mutations and polymorphisms have previously been reported in various ethnic groups, the current study identified, for the first time to the best of our knowledge, two novel BEST1 gene mutations in patients with BVMD. PMID:25936525

  11. [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. PMID:26847235

  12. Intracranial Artery Calcification and Its Clinical Significance

    PubMed Central

    Wu, Xiao Hong; Wang, Li Juan; Wong, Ka Sing

    2016-01-01

    Intracranial arterial calcification (IAC) is an easily identifiable entity on plain head computed tomography scans. Recent studies have found high prevalence rates for IAC worldwide, and this may be associated with ischemic stroke and cognitive decline. Aging, traditional cardiovascular risk factors, and chronic kidney disease have been found to be associated with IAC. The severity of IAC can be assessed using different visual grading scales or various quantitative methods (by measuring volume or intensity). An objective method for assessing IAC using consistent criteria is urgently required to facilitate comparisons between multiple studies involving diverse populations. There is accumulating evidence from clinical studies that IAC could be utilized as an indicator of intracranial atherosclerosis. However, the pathophysiology underlying the potential correlation between IAC and ischemic stroke—through direct arterial stenosis or plaque stability—remains to be determined. More well-designed clinical studies are needed to explore the predictive values of IAC in vascular events and the underlying pathophysiological mechanisms. PMID:27165425

  13. Drug chirality and its clinical significance.

    PubMed

    Hutt, A J; Tan, S C

    1996-01-01

    Approximately 1 in 4 therapeutic agents are marked as racemic mixtures, the individual enantiomers of which frequently differ in both their pharmacodynamic and pharmacokinetic profiles. The use of racemates has become the subject of considerable discussion in recent years, and an area of concern for both the pharmaceutical industry and regulatory authorities. The use of single enantiomers has a number of potential clinical advantages, including an improved therapeutic/pharmacological profile, a reduction in complex drug interactions, and simplified pharmacokinetics. In a number of instances stereochemical considerations have contributed to an understanding of the observed pharmacological effects of a drug administered as a racemate. However, relatively little is known of the influence of patient factors (e.g. disease state, age, gender and genetics) on drug enantiomer disposition and action in man. Examples may also be cited where the use of a single enantiomers, nonracemic mixtures and racemates of currently used agents may offer clinical advantages. The issues associated with drug chirality are complex and depend upon the relative merits of the individual agent. In the future it is likely that a number of existing racemates will be re-marketed as single enantiomer products with potentially improved clinical profiles and possible novel therapeutic indications. PMID:8922553

  14. Clinical Outcomes of Eyes with Submacular Hemorrhage Secondary to Age-related Macular Degeneration Treated with Anti-vascular Endothelial Growth Factor

    PubMed Central

    Kim, Kun Hae; Chang, Young Suk; Lee, Tae Gon; Kim, Jong Woo; Lew, Young Ju

    2015-01-01

    Purpose To evaluate the long-term outcomes of intravitreal anti-vascular endothelial growth factor (VEGF) monotherapy for patients diagnosed with submacular hemorrhage secondary to exudative age-related macular degeneration. Methods This retrospective, observational study included 49 patients (49 eyes) who initially presented with submacular hemorrhage associated with exudative age-related macular degeneration and who were followed-up for at least 24 months. Only eyes that were treated with intravitreal anti-VEGF monotherapy were included in the study. Best-corrected visual acuity (BCVA) measurements obtained at diagnosis, six months, and the final visit were compared. The associations of BCVA at the final visit with baseline BCVA, BCVA at six months, symptom duration, hemorrhage extent, and central foveal thickness were also analyzed. Results Over the course of follow-up (mean, 32.1 ± 8.5 months), an average of 5.1 ± 2.2 anti-VEGF injections were administered. Recurrent hemorrhage was noted in 13 eyes (26.5%). The mean logarithm of the minimal angle of resolution BCVA at diagnosis, six months, and the final visit were 1.40 ± 0.52, 0.87 ± 0.64, and 1.03 ± 0.83, respectively. Both baseline BCVA (p = 0.012) and BCVA at six months (p < 0.001) were significantly associated with BCVA at the final visit. Conclusions Improved visual acuity was maintained for more than two years with intravitreal anti-VEGF monotherapy. BCVA at six months is a useful clinical index to predict long-term visual prognosis. PMID:26457037

  15. 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

  16. 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

  17. Clinically significant factors in dowel design.

    PubMed

    Sorensen, J A; Martinoff, J T

    1984-07-01

    When a method of intracoronal reinforcement is selected, many factors must be weighed. The hazards include (1) the induced stresses and the risk of fracture during placement of the dowel, (2) the probability of root perforation during post space preparation, (3) the wedging action of tapered dowels, and (4) the incidence of fracture with self-threading pins in devitalized teeth. The amount of tooth structure that remains after endodontic therapy and post space preparation is paramount. Endodontic and restorative treatment must be aimed at preserving tooth structure to provide strength and resistance to fracture of the pulpless tooth. To fabricate a large-diameter dowel with a strength that greatly exceeds that of the endodontically treated root decreases the prognosis for clinical success. PMID:6379161

  18. 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

  19. Clinically detectable drusen domains in fibulin-5-associated age-related macular degeneration (AMD) : Drusen subdomains in fibulin-5 AMD.

    PubMed

    Kucukevcilioglu, Murat; Patel, Chetankumar B; Stone, Edwin M; Russell, Stephen R

    2016-08-01

    To evaluate whether drusen of subjects with fibulin-5 mutation-associated age-related macular degeneration (AMD) have clinically demonstrable drusen domains as evidenced by differences between color and fluorescein angiographic profiles. Of seven patients we identified with AMD due to mutations in the fibulin-5 gene (Fib-5 AMD), five had color fundus photography and fluorescein angiography (FA). One had bilateral choroidal neovascularization and no drusen. For each eye, the green channel (GC) of the digital RGB (Red-Green-Blue) color image and hyperfluorescent domain (HD) intensity of the FA image were registered and drusen were manually segmented and measured. Totally 75 small (≤62 μm), 110 intermediate (63-125 μm), and 30 large (>125 μm) drusen were measured in four patients within the 6 × 6 mm central macular areas. All four subjects demonstrated central or paracentral HDs within each drusen perimeter. HDs were found in association with each druse, with a HD/GC ratio of 0.82, 0.76, and 0.72 respectively for small, intermediate, and large drusen (Student T Test: P < 0.01, P < 0.01, P < 0.01). A statistical difference was found for the HD/GC ratios between small- and intermediate-sized drusen and small- and large-sized drusen but not between intermediate-sized and large-sized drusen (P = 0.001, P < 0.001, P > 0.05, respectively). AMD patients with mutations in fibulin-5 share drusen phenotypic structure and have HD/GC ratios that are similar to individuals with cuticular or basal laminar drusen. Drusen substructure may reflect similarities in drusen stage and/or genesis and appear to vary among AMD genotypes. PMID:26694911

  20. Macrolide antibacterials. Drug interactions of clinical significance.

    PubMed

    von Rosensteil, N A; Adam, D

    1995-08-01

    Macrolide antibiotics can interact adversely with commonly used drugs, usually by altering metabolism due to complex formation and inhibition of cytochrome P-450 IIIA4 (CYP3A4) in the liver and enterocytes. In addition, pharmacokinetic drug interactions with macrolides can result from their antibiotic effect on microorganisms of the enteric flora, and through enhanced gastric emptying due to a motilin-like effect. Macrolides may be classified into 3 different groups according to their affinity for CYP3A4, and thus their propensity to cause pharmacokinetic drug interactions. Troleandomycin, erythromycin and its prodrugs decrease drug metabolism and may produce drug interactions (group 1). Others, including clarithromycin, flurithromycin, midecamycin, midecamycin acetate (miocamycin; ponsinomycin), josamycin and roxithromycin (group 2) rarely cause interactions. Azithromycin, dirithromycin, rikamycin and spiramycin (group 3) do not inactivate CYP3A4 and do not engender these adverse effects. Drug interactions with carbamazepine, cyclosporin, terfenadine, astemizole and theophylline represent the most frequently encountered interactions with macrolide antibiotics. If the combination of a macrolide and one of these compounds cannot be avoided, serum concentrations of concurrently administered drugs should be monitored and patients observed for signs of toxicity. Rare interactions and those of dubious clinical importance are those with alfentanil and sufentanil, antacids and cimetidine, oral anticoagulants, bromocriptine, clozapine, oral contraceptive steroids, digoxin, disopyramide, ergot alkaloids, felodipine, glibenclamide (glyburide), levodopa/carbidopa, lovastatin, methylprednisolone, phenazone (antipyrine), phenytoin, rifabutin and rifampicin (rifampin), triazolam and midazolam, valproic acid (sodium valproate) and zidovudine. PMID:7576262

  1. [Microbiologic and clinical significance of cefotiam].

    PubMed

    Tauchnitz, C; Ezold, R; Bauer, I; Berger, H D; Buhl, C; Goedecke, A; Morawietz, I

    1985-03-01

    Modern cephalosporins are of considerable importance for the therapy of severe infections by multiresistant organisms. According to in-vitro-findings on ampicillin-resistant E. coli as well as Klebsiella spp., Proteus spp., and serratia spp., altogether 159 strains, instead of cefotaxime nearly always also cefotiam can be used. The two remedies are clearly superior to cephalothin. cefotiam is ineffective to Pseudomonas aeruginosa. But in this case also cefotaxime is clearly inferior to azlocillin. In 6 of 7 casuistic instances the clinical effectiveness of cefotiam could be confirmed with good tolerability. The contemporary establishment of staph. aureus in mixed infections of serratiastaphylococci proved as as particular advantage. A primary therapeutic failure referred to a necrotizing pancreatitis, when no causative organism was proved, in which case also cefotaxime remained without any effect. Despite the improved individual medical possibilities the control of the infectious hospitalism by critical administration of antibiotics and improved hospital hygiene, particularly strict non-infection, must remain the pre-eminent task. PMID:3857792

  2. Lupus thrombocytopenia: clinical implications and prognostic significance

    PubMed Central

    Ziakas, P; Giannouli, S; Zintzaras, E; Tzioufas, A; Voulgarelis, M

    2005-01-01

    Methods: 632 patients were reviewed retrospectively. Fifty patients with thrombocytopenia were included as cases and matched with 100 control patients. Clinical manifestations at first thrombocytopenic episode were recorded. Classification criteria at diagnosis, basic immunological profiles, disease activity (ECLAM), and end organ damage (SLICC) were recorded. Results: 29/50 (58%) had thrombocytopenia at diagnosis of lupus. Haemorrhagic manifestations were associated with the degree of thrombocytopenia (p<0.001). Anticardiolipin antibodies were not related to the degree of thrombocytopenia or the severity of haemorrhagic manifestations. Megakaryocytes were normal or increased in 26/28 (93%) bone marrow specimens, indicating peripheral platelet destruction. Patients with high disease activity were more thrombocytopenic than controls (OR = 2.61, 95% CI 1.13 to 5.96, p = 0.009). Patients with low C3 or CH50 were more likely to be thrombocytopenic (OR = 2.36, 95% CI 1.05 to 5.26, p = 0.029). Median SLICC for lupus patients with thrombocytopenia was 2 (range 0–11) compared with 1 (range 0–12) for controls (p<0.001). No deaths occurred during thrombocytopenic episodes. Conclusions: Thrombocytopenia is not directly associated with end organ damage and mortality, but defines a subgroup of patients with higher morbidity and is thus a major complication of systemic lupus erythematosus, affecting overall prognosis. PMID:16100344

  3. 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

  4. Critical appraisal of the clinical utility of the dexamethasone intravitreal implant (Ozurdex®) for the treatment of macular edema related to branch retinal vein occlusion or central retinal vein occlusion

    PubMed Central

    Chan, Annie; Leung, Loh-Shan; Blumenkranz, Mark S

    2011-01-01

    Macular edema is a common cause of visual loss in patients with retinal vein occlusions. Ozurdex®, a dexamethasone intravitreal implant, has been shown in randomized controlled trials to reduce macular edema and improve visual acuity in patients with either branch retinal vein occlusions or central retinal vein occlusions. It was approved in the United States in 2009. Since then, new therapeutic agents and clinical data have emerged. The purpose of this review is to critically evaluate the clinical utility of Ozurdex® in the current treatment strategy of macular edema related to retinal vein occlusion. PMID:21845032

  5. Management of pseudophakic cystoid macular edema.

    PubMed

    Guo, Suqin; Patel, Shriji; Baumrind, Ben; Johnson, Keegan; Levinsohn, Daniel; Marcus, Edward; Tannen, Brad; Roy, Monique; Bhagat, Neelakshi; Zarbin, Marco

    2015-01-01

    Pseudophakic cystoid macular edema (PCME) is a common complication following cataract surgery. Acute PCME may resolve spontaneously, but some patients will develop chronic macular edema that affects vision and is difficult to treat. This disease was described more than 50 years ago, and there are multiple options for clinical management. We discuss mechanisms, clinical efficacy, and adverse effects of these treatment modalities. Topical non-steroidal anti-inflammatory agents and corticosteroids are widely used and, when combined, may have a synergistic effect. Intravitreal corticosteroids and anti-vascular endothelial growth factor (anti-VEGF) agents have shown promise when topical medications either fail or have had limited effects. Randomized clinical studies evaluating anti-VEGF agents are needed to fully evaluate benefits and risks. When PCME is either refractory to medical therapy or is associated with significant vitreous involvement, pars plana vitrectomy has been shown to improve outcomes, though it is associated with additional risks. PMID:25438734

  6. Clinical significance of severe isolated diaphragm weakness.

    PubMed

    Laroche, C M; Carroll, N; Moxham, J; Green, M

    1988-10-01

    We studied six patients with isolated bilateral paralysis or severe weakness of the diaphragm, present for 2 to 60 months (mean = 25), to document the clinical and respiratory sequelae of the condition. Severe diaphragm dysfunction was confirmed by the demonstration of the very low maximal transdiaphragmatic pressure (Pdi) generated by either a sniff (13 +/- 6 cm H2O, normal 148 +/- 24) or a static inspiration (11 +/- 8, normal 108 +/- 30) and during bilateral phrenic nerve stimulation (0.8 +/- 2.0, normal 22 +/- 4). Resting arterial blood gases were normal (SaO2 = 95 to 97%) and no oxygen desaturation occurred during maximal exercise on a treadmill. Maximum voluntary ventilation was low and related to PImax (r = 0.89). Overnight sleep monitoring showed that time spent in rapid eye movement sleep was normal (mean 55 +/- 36 min, range 26 to 117 min). Mean maximum increment in transcutaneous CO2 was within normal limits (6 +/- 2 mm Hg, range 3 to 9 mm Hg). Three patients had occasional brief episodes of oxygen desaturation (mean maximal decrease 13 +/- 10%, range 2 to 27%); however, only two of these spent a measurable proportion of total sleep time (TST) with an SaO2 of less than 80% (1% and 3% TST, respectively). No patient has developed any symptoms of nocturnal hypoventilation or chronic respiratory failure during periods of observation of up to five yr. We conclude that bilateral paralysis or very severe weakness of the diaphragm does not of itself lead to respiratory failure unless weakness of other respiratory muscles is present. PMID:3202460

  7. [Review and expert opinion in age related macular degeneration. Focus on the pathophysiology, angiogenesis and pharmacological and clinical data].

    PubMed

    Weber, M; Sennlaub, F; Souied, E; Cohen, S-Y; Béhar-Cohen, F; Milano, G; Tadayoni, R

    2014-09-01

    Age related macular degeneration (AMD) is a pathological aging of the macula, brought about by the interaction of genetic and environmental factors. It induces geographic atrophy of the retina and/or choroidal neovascularization. In the latter, abnormal vessels develop from the choriocapillaris, with the involvement of VEGF (vascular endothelial growth factor). The VEGF family includes several factors, including VEGF-A, B, C, D, F and PlGF (placental growth factor). Their biological properties and their affinities to the VEGFR1, VEGFR2 and VEGFR3 receptors found on endothelial cells differ. Exudative AMD involves mainly VEGF-A and VEGF-R2. Anti-VEGF agents used in ophthalmology (ranibizumab, bevacizumab and aflibercept) are designed to primarily target this pathway. In vitro, all have sufficient affinity to their ligands. Their therapeutic efficacy must therefore be judged based on clinical criteria. In clinical practice, the minimum number of injections required for a satisfactory result appears to be comparable with all the three. The few available studies on therapeutic substitutions of anti-VEGF compounds suggest that some patients may benefit from substituting the anti-VEGF in cases of an unsatisfactory response to an initial molecule. Although local side effects, including increased risk of geographic atrophy, and systemic effects, including vascular accidents, have been suggested, these risks remain low, specially compared to the benefits of the treatment. Differences in safety between anti-VEGF are theoretically possible but unproven. PMID:25190312

  8. 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. PMID:24732758

  9. Effects of major ozonated autohemotherapy in the treatment of dry age related macular degeneration: a randomized controlled clinical study

    PubMed Central

    Borrelli, Emma; Diadori, Angelica; Zalaffi, Alessandro; Bocci, Velio

    2012-01-01

    AIM To evaluate the effect of systemic ozonated major autohaemotherapy (O3-AHT) in patients affected by dry age related macular degeneration (AMD). METHODS This study was a randomized, controlled clinical study. One hundred and forty patients with the diagnosis of AMD in both eyes, with the study eye presenting dry AMD and soft drusen, were randomly assigned in a 1:1 ratio to either receive 27 major ozonated autohemotherapy treatments during 12-month period, or a standardized multi-vitamin therapy. Primary outcome was the change in best corrected visual acuity (mean logMar change) between the baseline and 6 and 12 months, end point of the study. In addition, to investigate the safety of prolonged ozonated autohaemotherapy, we measured the routine haematochemical parameters and biochemical oxidative stress values at baseline and after 12 months treatment time. RESULTS The mean baseline best corrected visual acuity in study eyes was 0.36 in the treatment group and 0.38 in the control group (difference not statistically significant). At the primary endpoint, 6 months post-baseline, the mean logMAR change in the treated group improved by 0.1 and the values of the control group at the same time impaired by 0.2 respect to the baseline. Four percent and twenty-five percent of eyes in the group treated with O3-AHT gained 1 or more lines after 6 and 12 months respectively compared to 0% in the eyes which received no treatment (P<0.05 at 12 months). None of the treated patients experienced a loss in visual acuity in their study eye at 6 and 12 months, compared to 16% and 40 % of patients in the control group who lost 2 lines or more at 6 months and 12 months respectively (P<0.05 treated vs control group)). Major ozonated autohemotherapy was shown to be safe and well- tolerated by the patients. Moreover, the haematochemical parameters showed a decrease in the Reactive Oxygen Metabolites (300±10.1 UCARR at 12 months compared to a baseline value of 380±10.4 UCARR, P<0.05) and

  10. 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

  11. Scanning laser tomography Z profile signal width as an objective index of macular retinal thickening

    PubMed Central

    Hudson, C.; Flanagan, J.; Turner, G.; McLeod, D.

    1998-01-01

    AIMS—(i) To evaluate the relation between retinal thickness and the Z profile signal width of a scanning laser tomographer in selected patients exhibiting clinically manifest and circumscribed macular retinal thickening; (ii) to compare the Z profile signal width values of a group of age similar normal subjects with those of the patients with macular retinal thickening; and (iii) to present the methodology underlying the Z profile signal width derivation.
METHODS—Three patients with the following conditions were selected: widespread diabetic macular oedema; localised diabetic macular oedema; and macular hole. The patients were selected because they exhibited clinically manifest and circumscribed macular retinal thickening. Patients underwent fundus photography and a clinical examination which included fundus biomicroscopy. Fourteen age similar normal subjects were also assessed. The Heidelberg retina tomograph (HRT) was utilised to acquire seven topographic images of each macula. Z profile signal width data were analysed using custom software. Signal width was measured at 50% of the maximum intensity.
RESULTS—For each patient with macular retinal thickening, Z profile signal width analysis (after normalisation to reduce the influence of variation in reflectance intensity between successive images) revealed a significant (p<0.0001) localised increase of signal width which agreed with the HRT topographic analysis of retinal height, and also the clinical assessment of retinal thickness. The mean normalised Z profile signal width for the normal subjects (assessed over the whole image) ranged from 0.278 (SD 0.039) to 0.444 (0.063); these values compared with those obtained from patients in areas of macular retinal thickening of 0.761 (0.224) to 0.953 (0.194). Z profile signal width test-retest data for the patient with localised diabetic macular oedema were plus or minus 0.159 which compared with a mean signal width value of 0.761.

  12. Macular Degeneration

    MedlinePlus

    ... common early symptom. Dry AMD happens when the light-sensitive cells in the macula slowly break down. Your gradually lose your central vision. A common early symptom is that straight lines appear crooked. Regular comprehensive eye exams can detect macular degeneration before the disease ...

  13. 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 ...

  14. Progressive Macular Hypomelanosis in Korean Patients: A Clinicopathologic Study

    PubMed Central

    Hwang, Seon Wook; Hong, Soon Kwon; Kim, Sang Hyun; Park, Jeong Hoon; Seo, Jong Keun; Sung, Ho Suk

    2009-01-01

    Background Progressive macular hypomelanosis is characterized by ill-defined, non-scaly, hypopigmented macules primarily on the trunk of the body. Although numerous cases of progressive macular hypomelanosis have been reported, there have been no clinicopathologic studies of progressive macular hypomelanosis in Korean patients. Objective In this study we examined the clinical characteristics, histologic findings, and treatment methods for progressive macular hypomelanosis in a Korean population. Methods Between 1996 and 2005, 20 patients presented to the Department of Dermatology at Busan Paik Hospital with acquired, non-scaly, confluent, hypopigmented macules on the trunk, and with no history of inflammation or infection. The medical records, clinical photographs, and pathologic findings for each patient were examined. Results The patients included 5 men and 15 women. The mean age of onset was 21.05±3.47 years. The back was the most common site of involvement. All KOH examinations were negative. A Wood's lamp examination showed hypopigmented lesions compared with the adjacent normal skin. A microscopic examination showed a reduction in the number of melanin granules in the lesions compared with the adjacent normal skin, although S-100 immunohistochemical staining did not reveal significant differences in the number of melanocytes. Among the 20 patients, 7 received topical drug therapy, 6 were treated with narrow-band ultraviolet B phototherapy, 4 received oral minocycline, and 3 did not receive any treatment. Conclusion Most of the patients with progressive macular hypomelanosis had asymptomatic ill-defined, non-scaly, and symmetric hypopigmented macules, especially on the back and abdomen. Histologically, the number of melanocytes did not differ significantly between the hypopigmented macules and the normal perilesional skin. No effective treatment is known for progressive macular hypomelanosis; however, narrow-band ultraviolet B phototherapy may be a useful

  15. Assessing clinical significance of treatment outcomes using the DASS-21.

    PubMed

    Ronk, Fiona R; Korman, James R; Hooke, Geoffrey R; Page, Andrew C

    2013-12-01

    Standard clinical significance classifications are based on movement between the "dysfunctional" and "functional" distributions; however, this dichotomy ignores heterogeneity within the "dysfunctional" population. Based on the methodology described by Tingey, Lambert, Burlingame, and Hansen (1996), the present study sought to present a 3-distribution clinical significance model for the 21-item version of the Depression Anxiety Stress Scales (DASS-21; P. F. Lovibond & Lovibond, 1995) using data from a normative sample (n = 2,914), an outpatient sample (n = 1,000), and an inpatient sample (n = 3,964). DASS-21 scores were collected at pre- and post-treatment for both clinical samples, and patients were classified into 1 of 5 categories based on whether they had made a reliable change and whether they had moved into a different functional range. Evidence supported the validity of the 3-distribution model for the DASS-21, since inpatients who were classified as making a clinically significant change showed lower symptom severity, higher perceived quality of life, and higher clinician-rated functioning than those who did not make a clinically significant change. Importantly, results suggest that the new category of recovering is an intermediate point between recovered and making no clinically significant change. Inpatients and outpatients have different treatment goals and therefore use of the concept of clinical significance needs to acknowledge differences in what constitutes a meaningful change. PMID:23730826

  16. 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. PMID:24469116

  17. 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. PMID:26518628

  18. Clinical and biological significance of aneuploidy in human tumours.

    PubMed Central

    Friedlander, M L; Hedley, D W; Taylor, I W

    1984-01-01

    Aneuploidy is a well recognised feature of human tumours, but the investigation of its biological and clinical significance has been hampered by technological constraints. Quantitative DNA analysis reflects the total chromosomal content of tumour cells and can now be determined rapidly and reliably using flow cytometry; this has resulted in renewed interest in its potential clinical applications. This article reviews the accumulating evidence that tumour ploidy reflects the biological behaviour of a large number of tumour types and that diploid tumours in particular have a relatively good prognosis. The measurement of tumour ploidy is likely to become a valuable adjunct to the clinical and histopathological assessment of cancers. PMID:6381555

  19. Reversible mechanisms of enzyme inhibition and resulting clinical significance.

    PubMed

    Ring, Barbara; Wrighton, Steven A; Mohutsky, Michael

    2014-01-01

    Inhibition of a drug-metabolizing enzyme by the reversible interaction of a drug with the enzyme, thus decreasing the metabolism of another drug, is a major cause of clinically significant drug-drug interactions. This chapter defines the four reversible mechanisms of inhibition exhibited by drugs: competitive, noncompetitive, uncompetitive, and mixed competitive/noncompetitive. An in vitro procedure to determine the potential of a drug to be a reversible inhibitor is also provided. Finally, a number of examples of clinically significant drug-drug interactions resulting from reversible inhibition are described. PMID:24523108

  20. Imaging polarimetry of macular disease

    NASA Astrophysics Data System (ADS)

    Miura, Masahiro; Elsner, Ann E.; Petrig, Benno L.; VanNasdale, Dean A.; Zhao, Yanming; Iwasaki, Takuya

    2008-02-01

    Polarization properties of the human eye have long been used to study the tissues of the human retina, as well as to improve retinal imaging, and several new technologies using polarized light are in use or under development. 1-8 The most typical polarimetry technique in ophthalmology clinic is a scanning laser polarimetry for the glaucoma diagnosis. 1,2 In the original conceptualization, the thickness of the retinal nerve fiber layer is estimated using the birefringent component of light returning from the ocular fundus. More recently, customized software to analyze data from scanning laser polarimetry was developed to investigate the polarization properties of the macular disease. 5-8 In this study, we analyzed macular disease with imaging polarimetry, which provides a method for the noninvasive assessment of macular disease.

  1. Achondroplasia and Macular Coloboma

    PubMed Central

    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. PMID:26692730

  2. 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. PMID:26692730

  3. Assessing Clinical Significance: Does it Matter which Method we Use?

    ERIC Educational Resources Information Center

    Atkins, David C.; Bedics, Jamie D.; Mcglinchey, Joseph B.; Beauchaine, Theodore P.

    2005-01-01

    Measures of clinical significance are frequently used to evaluate client change during therapy. Several alternatives to the original method devised by N. S. Jacobson, W. C. Follette, & D. Revenstorf (1984) have been proposed, each purporting to increase accuracy. However, researchers have had little systematic guidance in choosing among…

  4. Clinical Significance of Mycobacterium kansasii Isolates from Respiratory Specimens

    PubMed Central

    Jeon, Kyeongman; Kim, Su-Young; Chung, Myung Jin; Huh, Hee Jae; Ki, Chang-Seok; Lee, Nam Yong; Shin, Sung Jae; Koh, Won-Jung

    2015-01-01

    The clinical significance of Mycobacterium kansasii respiratory isolates is uncertain. The aims of this study were to determine the clinical relevance of M. kansasii isolates and to identify the clinical features and outcomes of M. kansasii lung disease. We reviewed the medical records of 104 patients from whom at least one respiratory M. kansasii isolate was obtained from January 2003 to July 2014 at Samsung Medical Center, South Korea. Of these 104 patients, 54 (52%) met the diagnostic criteria for nontuberculous mycobacterial lung disease; among them, 41 (76%) patients received antibiotic treatment for a median time of 15.0 months (interquartile range [IQR], 7.0–18.0 months). The remaining 13 (24%) without overt disease progression were observed for a median period of 24.0 months (IQR, 5.0–34.5 months). Patients with M. kansasii lung disease exhibited various radiographic findings of lung disease, including the fibrocavitary form (n = 24, 44%), the nodular bronchiectatic form (n = 17, 32%), and an unclassifiable form (n = 13, 24%). The fibrocavitary form was more common in patients who received treatment (n = 23, 56%), while the nodular bronchiectatic form was more common in patients with M. kansasii lung disease who did not receive treatment (n = 9, 70%). None of the patients with a single sputum isolate (n = 18) developed M. kansasii disease over a median follow-up period of 12.0 months (IQR, 4.0–26.5 months). In total, 52% of all patients with M. kansasii respiratory isolates exhibited clinically significant disease. Moreover, patients with M. kansasii lung disease displayed diverse radiographic findings in addition to the fibrocavitary form. The nodular bronchiectatic form was more common in patients with M. kansasii lung disease with an indolent clinical course. Thus, since the clinical significance of a single M. kansasii respiratory isolate is not definite, strict adherence to recommended diagnostic criteria is advised. PMID:26431540

  5. Bilateral Chondroepitrochlearis Muscle: Case Report, Phylogenetic Analysis, and Clinical Significance.

    PubMed

    Palagama, Sujeewa P W; Tedman, Raymond A; Barton, Matthew J; Forwood, Mark R

    2016-01-01

    Anomalous muscular variants of pectoralis major have been reported on several occasions in the medical literature. Among them, chondroepitrochlearis is one of the rarest. Therefore, this study aims to provide a comprehensive description of its anatomy and subsequent clinical significance, along with its phylogenetic importance in pectoral muscle evolution with regard to primate posture. The authors suggest a more appropriate name to better reflect its proximal attachment to the costochondral junction and distal attachment to the epicondyle of humerus, as "chondroepicondylaris"; in addition, we suggest a new theory of phylogenetic significance to explain the twisting of pectoralis major tendon in primates that may have occurred with their adoption to bipedalism and arboreal lifestyle. Finally, the clinical significance of this aberrant muscle is elaborated as a cause of potential neurovascular entrapment and as a possible hurdle during axillary surgeries (i.e., mastectomy). PMID:27242928

  6. Bilateral Chondroepitrochlearis Muscle: Case Report, Phylogenetic Analysis, and Clinical Significance

    PubMed Central

    Palagama, Sujeewa P. W.; Tedman, Raymond A.; Barton, Matthew J.; Forwood, Mark R.

    2016-01-01

    Anomalous muscular variants of pectoralis major have been reported on several occasions in the medical literature. Among them, chondroepitrochlearis is one of the rarest. Therefore, this study aims to provide a comprehensive description of its anatomy and subsequent clinical significance, along with its phylogenetic importance in pectoral muscle evolution with regard to primate posture. The authors suggest a more appropriate name to better reflect its proximal attachment to the costochondral junction and distal attachment to the epicondyle of humerus, as “chondroepicondylaris”; in addition, we suggest a new theory of phylogenetic significance to explain the twisting of pectoralis major tendon in primates that may have occurred with their adoption to bipedalism and arboreal lifestyle. Finally, the clinical significance of this aberrant muscle is elaborated as a cause of potential neurovascular entrapment and as a possible hurdle during axillary surgeries (i.e., mastectomy). PMID:27242928

  7. Unexpected Findings in Magnetic Resonance Enterography and Their Clinical Significance

    PubMed Central

    Ravindran, Srivathsan; Hancox, Sarah Helen; Barlow, Neil; Dunk, Arthur; Howlett, David

    2016-01-01

    Aims. To identify the prevalence of colonic and extraenteric incidental findings in magnetic resonance enterography (MRE) and their clinical significance. Methods. We retrospectively analysed 470 MRE studies carried out between March 2012 and 2014. Incidental findings were defined as those not expected from or made apparent on the referral. MRE reports were reviewed for colonic and extraenteric findings, subcategorised into “clinically significant” and “insignificant.” Follow-up was identified from the electronic patient record. Results. The majority of MRE requests were made for inflammatory bowel disease (97%). In total, 114 incidental findings were noted in 94 (20%) scans performed. There were 29 “colonic” findings (25%) with 55% having a diagnosis of colitis. Out of 85 extraenteric findings, ovarian cysts (25%), renal cysts (10%), and abdominal lymphadenopathy (9%) were the commonest. Cumulatively, 59 cases were clinically significant (52%); of these, 30 findings were not previously diagnosed, amounting to 26% of all incidental findings. This led to intervention in seven patients. Conclusions. Incidental findings are common in MRE and there is a substantial proportion that is clinically significant and requires further investigation. There need to be stratification of risk and employment of local guidelines in order to achieve this. PMID:27446837

  8. One-year outcome of bevacizumab therapy for chronic macular edema in central and branch retinal vein occlusions in real-world clinical practice in the UK

    PubMed Central

    Lip, Peck Lin; Malick, Huzaifa; Damer, Kenan; Elsherbiny, Samer; Darrad, Kanupriya M; Mushtaq, Bushra; Mitra, Arijit; Stavrou, Panagiota; Yang, Yit

    2015-01-01

    Background The purpose of this study was to investigate the 12-month outcome of macular edema secondary to both chronic and new central and branch retinal vein occlusions treated with intravitreal bevacizumab in the real-life clinical setting in the UK. Methods Retrospective case notes analysis of consecutive patients with retinal vein occlusions treated with bevacizumab in 2010 to 2012. Outcome measures were visual acuity (measured with Snellen, converted into logMAR [logarithm of the minimum angle of resolution] for statistical calculation) and central retinal thickness at baseline, 4 weeks post-loading phase, and at 1 year. Results There were 56 and 100 patients with central and branch retinal vein occlusions, respectively, of whom 62% had chronic edema and received prior therapies and another 32% required additional laser treatments post-baseline bevacizumab. Baseline median visual acuity was 0.78 (interquartile range [IQR] 0.48–1.22) in the central group and 0.6 (IQR 0.3–0.78) in the branch group. In both groups, visual improvement was statistically significant from baseline compared to post-loading (P<0.001 and P=0.03, respectively), but was not significant by month 12 (P=0.058 and P=0.166, respectively); 30% improved by at least three lines and 44% improved by at least one line by month 12. Baseline median central retinal thickness was 449 μm (IQR 388–553) in the central group and 441 μm (IQR 357–501) in the branch group. However, the mean reduction in thickness was statistically significant at post-loading (P<0.001) and at the 12-month time point (P<0.001) for both groups. The average number of injections in 1 year was 4.2 in the central group and 3.3 in the branch group. Conclusion Our large real-world cohort results indicate that bevacizumab introduced to patients with either new or chronic edema due to retinal vein occlusion can result in resolution of edema and stabilization of vision in the first year. PMID:26445525

  9. Meconium in perinatal imaging: associations and clinical significance.

    PubMed

    Jerdee, Theodore; Newman, Beverley; Rubesova, Erika

    2015-04-01

    An abnormal location, distribution, volume, or appearance of meconium is associated with a spectrum of bowel abnormalities, including atresia, obstruction, perforation, fistula, aganglionosis, immaturity, and absorptive dysfunction. This review discusses the fetal and perinatal imaging of these entities, their differential diagnoses, clinical significance, and appropriate imaging workup. Understanding the spectrum of normal and abnormal, specific and nonspecific appearances of meconium and its associated abnormalities on imaging will provide a practical, useful framework for performing and interpreting imaging studies and guiding clinical management. PMID:26001945

  10. VITAMIN D DEFICIENCY IN NEOVASCULAR VERSUS NONNEOVASCULAR AGE-RELATED MACULAR DEGENERATION

    PubMed Central

    Itty, Sujit; Day, Shelley; Lyles, Kenneth W.; Stinnett, Sandra S.; Vajzovic, Lejla M.; Mruthyunjaya, Prithvi

    2014-01-01

    Purpose To compare 25-hydroxyvitamin D (25OHD) levels in patients with neovascular age-related macular degeneration (NVAMD) with patients with nonneovascular age-related macular degeneration and control patients. Methods Medical records of all patients diagnosed with age-related macular degeneration and tested for serum 25OHD level at a single medical center were reviewed. Control patients were selected from patients diagnosed with pseudophakia but without age-related macular degeneration. The lowest 25OHD level available for each patient was recorded. Results Two hundred sixteen patients with nonneovascular age-related macular degeneration, 146 with NVAMD, and 100 non–age-related macular degeneration control patients were included. The levels of 25OHD (mean ± SD) were significantly lower in NVAMD patients (26.1 ± 14.4 ng/mL) versus nonneovascular age-related macular degeneration (31.5 ± 18.2 ng/mL, P = 0.003) and control (29.4 ± 10.1 ng/mL, P = 0.049) patients. The prevalence of vitamin D insufficiency (<30 ng/mL 25OHD), deficiency (<20 ng/mL), and severe deficiency (<10 ng/mL) were highest in the NVAMD group. The highest quintile of 25OHD was associated with a 0.35 (95% confidence interval, 0.18– 0.68) odds ratio for NVAMD. Conclusion This is the largest study to compare 25OHD levels in patients with the different clinical forms of age-related macular degeneration. Mean 25OHD levels were lower and vitamin D deficiency was more prevalent in NVAMD patients. These associations suggest that further research is necessary regarding vitamin D deficiency as a potentially modifiable risk factor for the development of NVAMD. PMID:24946100

  11. 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.

  12. Clinical Significance of Endothelial Dysfunction in Essential Hypertension.

    PubMed

    Gkaliagkousi, Eugenia; Gavriilaki, Eleni; Triantafyllou, Areti; Douma, Stella

    2015-11-01

    The endothelium is recognized as a major determinant of vascular physiology and pathophysiology. Over the last few decades, a plethora of studies have implicated endothelial dysfunction in the progression of atherosclerosis and the subclinical target organ damage observed in essential hypertension. However, the clinical significance of diagnosing endothelial dysfunction in patients with essential hypertension remains under investigation. Although a number of vascular and non-vascular markers of endothelial dysfunction have been proposed, there is an ongoing quest for a marker in the clinical setting that is optimal, inexpensive, and reproducible. In addition, endothelial dysfunction emerges as a promising therapeutic target of agents that are readily available in clinical practice. In this context, a better understanding of its role in essential hypertension becomes of great importance. Here, we aim to investigate the clinical significance of endothelial dysfunction in essential hypertension by accumulating novel data on (a) early diagnosis using robust markers with prognostic value in cardiovascular risk prediction, (b) the association of endothelial dysfunction with subclinical vascular organ damage, and (c) potential therapeutic targets. PMID:26371063

  13. 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].

  14. Ocular features in Alport syndrome: pathogenesis and clinical significance.

    PubMed

    Savige, Judy; Sheth, Shivanand; Leys, Anita; Nicholson, Anjali; Mack, Heather G; Colville, Deb

    2015-04-01

    Alport syndrome is an inherited disease characterized by progressive renal failure, hearing loss, and ocular abnormalities. Mutations in the COL4A5 (X-linked), or COL4A3 and COL4A4 (autosomal recessive) genes result in absence of the collagen IV α3α4α5 network from the basement membranes of the cornea, lens capsule, and retina and are associated with corneal opacities, anterior lenticonus, fleck retinopathy, and temporal retinal thinning. Typically, these features do not affect vision or, in the case of lenticonus, are correctable. In contrast, the rarer ophthalmic complications of posterior polymorphous corneal dystrophy, giant macular hole, and maculopathy all produce visual loss. Many of the ocular features of Alport syndrome are common, easily recognizable, and thus, helpful diagnostically, and in identifying the likelihood of early-onset renal failure. Lenticonus and central fleck retinopathy strongly suggest the diagnosis of Alport syndrome and are associated with renal failure before the age of 30 years, in males with X-linked disease. Sometimes, ophthalmic features suggest the mode of inheritance. A peripheral retinopathy in the mother of a male with hematuria suggests X-linked inheritance, and central retinopathy or lenticonus in a female means that recessive disease is likely. Ocular examination, retinal photography, and optical coherence tomography are widely available, safe, fast, inexpensive, and acceptable to patients. Ocular examination is particularly helpful in the diagnosis of Alport syndrome when genetic testing is not readily available or the results are inconclusive. It also detects complications, such as macular hole, for which new treatments are emerging. PMID:25649157

  15. 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.…

  16. 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. PMID:23583982

  17. Clinical significance in COPD patients followed in a real practice

    PubMed Central

    2013-01-01

    Background Chronic obstructive pulmonary disease (COPD) is an important public health issue in many countries which is estimated to become the fifth cause of disability and the third cause of mortality in the world within 2020. The objective of this study was to identify the clinical characteristics in the real clinical practice of a sample of patients with COPD followed in a pulmonology clinic. Methods The initial sample contained 207 subjects with respiratory claims that searched for specialized treatment and initiated regular monitoring between 2004 and 2009 in a private clinic localized in Cascavel, in the state of Parana, Brazil. Demographic data (weight, height, body mass index - BMI), history of comorbidities, use of respiratory and non respiratory drugs were also registered. Results The main cause related to the development of COPD was current or prior smoking (92.0%); the most frequently reported symptom was dyspnea (95.0%), followed by cough (86.1%), wheezing (69.4%) and sputum production (40.0%). During the follow up, 51 patients developed the need for oxygen therapy (28.3%). In 96 patients, there were periods of acute exacerbation, resulting in 37 hospitalizations. In addition to COPD, a significant number of comorbidities were identified, being cardiovascular disease and neurological disorders the most prevalent ones. Conclusions Based on the data collected, we could outline the profile of patients with COPD, showing characteristics of an elderly population, with multiple comorbidities, suggesting a health related quality of life lower than expected. PMID:23806051

  18. INTRAVITREAL DICLOFENAC VERSUS INTRAVITREAL TRIAMCINOLONE FOR THE TREATMENT OF UVEITIC CYSTOID MACULAR EDEMA.

    PubMed

    Soheilian, Masoud; Eskandari, Armen; Ramezani, Alireza; Rabbanikhah, Zahra; Esmaeilpour, Nasim F; Soheilian, Roham

    2013-04-11

    PURPOSE:: To compare the effect of intravitreal diclofenac (IVD) versus intravitreal triamcinolone (IVT) on refractory uveitic cystoid macular edema. METHODS:: In this pilot, randomized, clinical trial, 15 eyes were randomly assigned to IVD group, patients (8 eyes) who received a single intravitreal injection of diclofenac (500 μg/0.1 mL), and IVT group (7 eyes) patients who received a single intravitreal injection of triamcinolone (2 mg). Change in best-corrected visual acuity in logarithm of the minimum angle of resolution at Week 36 was the primary outcome measure. Secondary outcomes included changes in best-corrected visual acuity (BCVA) at 12 weeks and 24 weeks, central macular thickness, macular leakage, and potential injection-related complications. RESULTS:: In the IVD group, BCVA was more than the baseline values in 4 eyes at 36 weeks; however, within-group analysis disclosed no statistically significant changes in the mean BCVA in this group. Nonetheless, in the IVT group, mean BCVA improved significantly at 12, 24, but not at 36 weeks compared with the baseline values. It was 0.86 ± 0.37 at baseline and 0.63 ± 0.48, 0.62 ± 0.42, and 0.43 ± 0.49 logarithm of the minimum angle of resolution at 12, 24, and 36 weeks, respectively. Mean central macular thickness diminished also significantly only in the IVT group. Nevertheless, comparing the mean BCVA and central macular thickness changes, macular leakage, and the occurrence of any injection-related complications, no significant difference was observed between the groups at any of the follow-up visits. CONCLUSION:: This pilot study demonstrated the superiority of IVT over IVD in the treatment of refractory uveitic cystoid macular edema regarding both functional and anatomical outcomes. Further studies are warranted to confirm potential benefit of IVD observed in this study. PMID:23584700

  19. Clinical significance of lymph node micrometastasis in gastric cancer.

    PubMed

    Arigami, Takaaki; Uenosono, Yoshikazu; Yanagita, Shigehiro; Nakajo, Akihiro; Ishigami, Sumiya; Okumura, Hiroshi; Kijima, Yuko; Ueno, Shinichi; Natsugoe, Shoji

    2013-02-01

    Recently, the existence of lymph node micrometastasis (LNM), including isolated tumor cells, has been focused on during the development of molecular diagnostic tools for lymph node metastasis in various malignant neoplasms. In particular, immunohistochemistry and reverse transcription-polymerase chain reaction have been reported to be available for the detection of LNM in gastric cancer. However, at present, the clinical significance of LNM remains unclear in patients with gastric cancer. Therefore, we cannot strategically make light of this issue in clinical management. Currently, minimally invasive treatments, such as endoscopic submucosal dissection and laparoscopic surgery with personalized lymphadenectomy, are widely performed in consideration of postsurgical quality of life (QOL). However, it is important to maintain the balance between QOL and curability when selecting surgical treatments for patients with gastric cancer. If minimally invasive surgery based on LNM status was established for patients with early gastric cancer, it could be performed safely. We reviewed the clinical significance of LNM as an important strategic target in patients with gastric cancer. PMID:22546997

  20. 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

  1. Visual prosthetic device for bilateral end-stage macular degeneration.

    PubMed

    Chun, Dal W; Heier, Jeffrey S; Raizman, Michael B

    2005-11-01

    Age-related macular degeneration is the leading cause of blindness in the USA. For the 1.8 million patients in the most advanced stages, there are currently no available treatments to improve vision. A visual prosthetic device that provides one eye with an enlarged retinal image of the central visual field has been developed with the goal of improving central vision in patients with bilateral end-stage macular degeneration. The other eye is left unimplanted to provide peripheral vision. This device is designed for implantation in the posterior chamber of the eye during an outpatient surgical procedure. In US Food and Drug Administration clinical trials, 72% of patients experienced an improvement in their level of visual impairment (profound or severe, to severe or moderate). This was accompanied by a clinically significant improvement in quality of life. PMID:16293092

  2. Lack of clinically significant drug interactions between nevirapine and buprenorphine.

    PubMed

    McCance-Katz, Elinore F; Moody, David E; Morse, Gene D; Ma, Qing; Rainey, Petrie M

    2010-01-01

    This study was conducted to determine whether drug interactions of clinical importance occur between buprenorphine, an opioid partial agonist medication used in treatment of opioid dependence, and the nonnucleoside reverse transcriptase inhibitor (NNRTI) nevirapine. Opioid-dependent, buprenorphine/naloxone-maintained, HIV-negative volunteers (n = 7) participated in 24-hour sessions to determine the pharmacokinetics of buprenorphine alone and of buprenorphine and nevirapine following administration of 200 mg nevirapine daily for 15 days. Opiate withdrawal symptoms, cognitive effects, and adverse events were determined prior to and following nevirapine administration. Modest decreases were observed for AUC for buprenorphine and its metabolites. There was a trend for more rapid clearance of both buprenorphine (p = .08) and buprenorphine-3-glucuronide (p = .08). While no single effect reached statistical significance, the joint probability that the consistent declines in all measures of exposure were due to chance was extremely low, indicating that nevirapine significantly reduces overall exposure to buprenorphine and buprenorphine metabolites. Clinically significant consequences of the interaction were not observed. Buprenorphine did not alter nevirapine pharmacokinetics. Dose adjustments of either buprenorphine or nevirapine are not likely to be necessary when these drugs are coadministered for the treatment of opiate dependence and HIV disease. PMID:20132119

  3. Clinical significance of pharmacokinetic interactions between antiepileptic and psychotropic drugs.

    PubMed

    Spina, Edoardo; Perucca, Emilio

    2002-01-01

    As antiepileptic drugs (AEDs) and psychotropic agents are increasingly used in combination, the possibility of pharmacokinetic interactions between these compounds is relatively common. Most pharmacokinetic interactions between AEDs and psychoactive drugs occur at a metabolic level, and usually involve changes in the activity of the cytochrome P450 mixed-function oxidases (CYP) involved in their biotransformation. As a consequence of CYP inhibition or induction, plasma concentrations of a given drug may reach toxic or subtherapeutic levels, and dosage adjustments may be required to avoid adverse effects or clinical failure. Enzyme-inducing AEDs, such as carbamazepine (CBZ), phenytoin (PHT), and barbiturates, stimulate the oxidative biotransformation of many concurrently prescribed psychotropics. In particular, these AEDs may decrease the plasma concentrations of tricyclic antidepressants, many antipsychotics, including traditional compounds, i.e., haloperidol and chlorpromazine, and newer agents, i.e., clozapine, risperidone, olanzapine, quetiapine, and ziprasidone, and some benzodiazepines. Conversely, new AEDs appear to have a lower potential for interactions with all psychotropic drugs. While antipsychotics and anxiolytics do not significantly influence the pharmacokinetics of most AEDs, some newer antidepressants, such as viloxazine, fluoxetine, and fluvoxamine, may lead to higher serum levels of some AEDs, namely CBZ and PHT, through inhibition of CYP enzymes. No significant pharmacokinetic interactions have been documented between AEDs and lithium. Information about CYP enzymes responsible for the biotransformation of individual agents and about the effects of these compounds on the activity of specific CYP enzymes may help in predicting and avoiding clinically significant interactions. Apart from careful clinical observation, serum level monitoring of AEDs and psychotropic drugs can be useful in determining the need for dosage adjustments, especially if

  4. Macular protection with IOLs

    NASA Astrophysics Data System (ADS)

    Soderberg, Per G.; Lofgren, Stefan; Ayala, Marcelo; Dong, Xiuqin; Kakar, Manoj; Mody, Vino; Meyer, Linda; Laurell, Carl-Gustaf

    2004-07-01

    The clinical outcome within one month after phacoemulsification cataract extraction with implantation of the blue-blocking SN60AT IOL was examined prospectively and compared to a retrospectively examined material of implantations of the equivalent SA30AL without blue-blocker. There was no difference in best corrected visual acuity gain between the two lenses. In addition, the subjective color perception was examined for with a questionnaire after the first implantation of blue-blocking IOL and after the second implantation of blue-blocking IOL. Only one patient noted a changed color perception. There are thus strong theoretical reasons to block blue light in IOLs and no short term clinical inconvenience. But, it remains to be proven in long term follow up studies that the blue-blocking IOL protects against macular degeneration.

  5. 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

  6. 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. PMID:25843911

  7. 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

  8. Macroscopic serosal classification of colorectal cancer and its clinical significance

    PubMed Central

    Wang, Yong-Peng; Guo, Peng-Tao; Zhu, Zhi; Zhang, Hao; Xu, Yan; Ma, Si-Ping; Wang, Zhen-Ning; Xu, Hui-Mian

    2015-01-01

    Background: Macroscopic serosal classification of gastric cancer has been reported in previous studies, but rarely reported about it of colorectal cancer. The purpose of this study was to propose a macroscopic serosal classification of colorectal cancer and to investigate clinical significance of this classification. Materials and methods: Morphologic features of colorectal cancer were analyzed according to the macroscopic serosal appearance and clinicopathologic characteristics of these patients were retrospectively reviewed. Microscopic serosal structure was compared between different types under light microscope and transmission electron microscope. Results: Macroscopic serosal classification was divided into normal type, reactive type, nodular type and colloid type according to the macroscopic serosal appearance and microscopic structure. There were significant differences in tumor size, tumor gross type, histological type, histological grade, tumor necrosis, pT stage, number of nodes metastasis, lymph node metastasis ratio, pN stage, M stage and peritoneal metastasis between patients with different serosal types. Univariate analysis of prognosis revealed macroscopic serosal classification as one of factors significantly correlated with patient survival. However, multivariate analysis only revealed TNM stage significantly correlated with patient survival, while macroscopic serosal classification did not, maybe due to insufficient samples. Conclusions: Macroscopic serosal classification of colorectal cancer is preliminarily defined and divided into four types. Different macroscopic serosal types indicate different clinicopathologic features and correlate with prognosis of patients with colorectal cancer, but still cannot be proven as an independent factor. PMID:26884925

  9. Expression and clinical significance of Nectin-4 in hepatocellular carcinoma

    PubMed Central

    Ma, Jie; Sheng, ZhiYong; Lv, Yang; Liu, WenBin; Yao, QiYang; Pan, TingTing; Xu, ZhiJun; Zhang, ChuanHai; Xu, GeLiang

    2016-01-01

    Objective Nectin-4 is a member of the Nectin family of four Ca+-independent immunoglobulin-like cell adhesion molecules and implicated in cell adhesion, movement, proliferation, differentiation, polarization, and survival. The aberrant expression of Nectin-4 has been found in a variety of tumors; however, its expression in hepatocellular carcinoma (HCC) is still poorly understood. This study was to investigate the expression of Nectin-4 and its clinical significance in the patients with HCC. Methods The expression of Nectin-4 was assessed at mRNA and protein levels by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting assays in 20 HCC specimens and adjacent non-tumor live tissues. Furthermore, the clinical significance of Nectin-4 in 87 cases of HCC was confirmed by immunohistochemistry. Results The mRNA and protein levels of Nectin-4 were higher in HCC tumor tissues than in the matched non-tumor tissues. Nectin-4 was located in the cytoplasm of tumor cells and over-expressed in 67.82% (59/87) HCC tissues by immunohistochemical staining. Positive Nectin-4 expression was significantly correlated with tumor size (P=0.029), status of metastasis (P=0.023), vascular invasion (P=0.018) and tumor-node-metastasis stage (P=0.003). In addition, Kaplan–Meier survival analysis indicated that positive Nectin-4 expression was associated with worse recurrence-free survival (RFS) and overall survival (OS) (P=0.006 and P=0.005, respectively). In multivariate analysis, Nectin-4 was an independent prognostic factor for RFS and OS in the patients with HCC. Conclusion Nectin-4 is upregulated in HCC and may be a novel prognostic biomarker for the patients after surgical resection. PMID:26793002

  10. Advances in the management of macular degeneration

    PubMed Central

    2014-01-01

    Current management of age-related macular degeneration (AMD) can be divided into two categories: first, anti-vasoendothelial growth factor (anti-VEGF) injection for wet macular degeneration; second, anti-oxidant vitamins for dry macular degeneration. New therapies are being developed for both of these diseases using novel technologies and different modes of administration. The hope is that some of these therapies will achieve significant improvement to current management and prevent future loss of vision in this devastating eye condition. PMID:24860651

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

    PubMed

    Nakamori, Kenji; Tomihara, Kei; Noguchi, Makoto

    2014-07-28

    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

  12. 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

  13. 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

  14. Imaging assessment and clinical significance of pneumatosis in adult patients.

    PubMed

    Lassandro, Francesco; Valente, Tullio; Rea, Gaetano; Lassandro, Giulia; Golia, Erica; Brunese, Luca; Laghi, Andrea

    2015-01-01

    Gas detection in the bowel wall and in portomesenteric venous vessels in adults has long been related to intestinal infarction and poor outcome; many case reports have shown that pneumatosis may be associated with a large variety of pathological situations, ranging from absolutely benign and asymptomatic forms to abdominal catastrophes. Several studies have been conducted on this topic with different conclusions, probably due to differences in population so that the clinical value of these signs is still questioned. Intestinal pneumatosis, especially if presenting with a band-like pattern and if associated with portomesenteric vein gas, when observed in an acute abdominal setting should raise the suspicion of mesenteric infarct and prompt a careful search for other signs of intestinal involvement, so as not to miss cases of life-threatening intestinal infarct or allow them to further evolve into extensive necrosis with worse prognosis. In this review we illustrate the most relevant aspects of these debated but significant radiological signs. PMID:25297049

  15. Clinical significance of serum claudin-1 levels in melanoma patients.

    PubMed

    Tas, Faruk; Bilgin, Elif; Erturk, Kayhan; Duranyildiz, Derya

    2016-08-01

    Claudins are the most important structural and functional components of tight-junction integral membrane proteins. They play roles in major cellular functions including growth and adhesion and are responsible for regulating the paracellular transport of molecules. The objective of this study was to determine the clinical significance of the serum levels of claudin-1, an oldest and important member of the claudin family, in melanoma patients. A total of 98 patients with a pathologically confirmed melanoma were enrolled into this study. Serum claudin-1 concentrations were determined by the solid-phase sandwich enzyme-linked immunosorbent assay method. Age-matched and sex-matched 43 healthy controls were included in the analysis. The median age at diagnosis was 51 years, ranging from 16 to 85 years. The majority of the patients were male (61%) and had axial localized (54%) and metastatic disease (61%). Moreover, most of the patients with metastatic disease had M1c (73%). The baseline serum claudin-1 levels of the melanoma patients were significantly lower than those of control subjects (median values 9.17 vs. 13.82 ng/ml, respectively, P<0.001). However, known clinical variables including age of the patient, sex, site of lesion, histology, lymph node involvement, stage of disease, serum lactate dehydrogenase levels, and response to chemotherapy were not found to be correlated with serum claudin-1 concentrations (P>0.05). Similarly, serum claudin-1 concentration was found to have no prognostic role in survival (P=0.524). In conclusion, serum levels of claudin-1 may have a diagnostic value in melanoma patients. However, its predictive and prognostic value has not been determined. PMID:26886788

  16. [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

  17. Expression and clinical significance of aquaglyceroporins in human hepatocellular carcinoma.

    PubMed

    Chen, Xiao-Feng; Li, Chuan-Fei; Lü, Lin; Mei, Zhe-Chuan

    2016-06-01

    Aquaglyceroporins (AQPs) are a subset of the aquaporin family, and are permeable to water and glycerol. The aim of the present study was to determine the expression and clinical significance of three AQPs, AQP3, 7 and 9 in hepatocellular carcinoma (HCC). Fresh HCC and adjacent non‑tumorous liver tissues were collected from 68 patients diagnosed with HCC. The expression levels of AQP3, 7 and 9 were detected by reverse transcription‑quantitative polymerase chain reaction, western blotting and immunohistochemical analysis. The association between the expression of AQPs and clinicopathological parameters of HCC were investigated. Compared with non‑tumorous liver tissue, HCC tissues exhibited a significant (P<0.05) increase in the expression of AQP3 and a concomitant reduction in the expression levels of AQP7 and AQP9, at both the mRNA and protein levels. Immunohistochemistry revealed that AQP9 was dominantly localized on the plasma membrane of hepatocytes, while AQP3 and AQP7 exhibited a predominantly cytoplasmic and nuclear distribution. High expression of AQP3 was significantly (P<0.05) associated with low expression levels of AQP7 and AQP9. High expression of AQP3 was correlated with tumor grade (P=0.017), tumor stage (P=0.010) and lymphatic metastasis (P=0.031). Low expression of AQP7 was correlated with tumor grade (P=0.043). AQP3 was upregulated, and AQP7 and AQP9 were downregulated in HCC. A high expression of AQP3 and low expression of AQP7 was significantly associated with the aggressive features of HCC. PMID:27121567

  18. 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.

  19. The clinical significance of patients’ sex in chronic lymphocytic leukemia

    PubMed Central

    Catovsky, Daniel; Wade, Rachel; Else, Monica

    2014-01-01

    We examined the prognostic influence of gender in chronic lymphocytic leukemia. Data from four randomized trials (involving 1821 patients) and three registration studies of stage-A disease (involving 1299 patients) were analyzed. Overall survival at 10 years was better for women than men in all trials (27% versus 15%; P=0.0001) and in the registration series (55% versus 43%; P<0.0001). More women than men in the trials were Binet stage A-progressive (26% versus 15%), but gender was an independent predictor of survival in multivariate analysis of clinical variables (P<0.0001). Women responded better to treatment (overall response 83%) than men (71%; P<0.0001), within each stage and age group, although fewer women than men received the full treatment dose (79% versus 85%; P=0.01). Women were more likely than men to experience toxicity (85% versus 78%, P=0.01), particularly gastro-intestinal toxicity (57% versus 42%, P<0.0001). Laboratory markers in the LRF CLL4 trial showed a significantly lower incidence in women than men of unmutated IGHV genes, raised beta-2 microglobulin, CD38 and Zap-70 positivity and TP53 deletions/mutations and/or 11q deletions. We also highlight the higher male:female ratios in randomized trials versus studies of early chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis. Chronic lymphocytic leukemia in women runs a more benign clinical course than in men. Gender was also an independent predictor of response, suggesting that pharmacokinetic differences between the sexes and a possible effect of estrogens may contribute to the better outcome. Understanding the reasons for the different outcome by gender may improve patients’ management. (LRF CLL4 controlled-trials.com identifier: ISRCTN58585610). PMID:24658818

  20. Clinical significance of circulating plasma DNA in gastric cancer.

    PubMed

    Fang, Wen-Liang; Lan, Yuan-Tzu; Huang, Kuo-Hung; Liu, Chien-An; Hung, Yi-Ping; Lin, Chien-Hsing; Jhang, Fang-Yu; Chang, Shih-Ching; Chen, Ming-Huang; Chao, Yee; Lin, Wen-Chang; Lo, Su-Shun; Fen-Yau Li, Anna; Wu, Chew-Wun; Chiou, Shih-Hwa; Shyr, Yi-Ming

    2016-06-15

    With the progression of molecular techniques, the detection of circulating plasma DNA (cpDNA) is clinically feasible. However, the role of the cpDNA levels in gastric cancer is not well understood. This study assessed the mutational profile in primary tumors and clarified the clinical utility of quantitative and qualitative cpDNA alterations in 277 patients with advanced gastric cancer. The concentrations of cpDNA were measured by TaqMan qPCR, and 68 mutations in 8 genes were studied for cpDNA mutations. The median cpDNA concentrations in patients with stages I, II, and III gastric cancer were 3979, 3390 and 4278 copies/mL, respectively, and increased to 11,380 copies/mL in patients with Stage IV gastric cancer (p < 0.001). Among the 35 patients harboring cpDNA mutations, Stage IV patients (100%) were more likely to display high cpDNA levels than were Stage I (33.3%), II (75%) and III patients (66.7%) (p = 0.037). Patients displaying high cpDNA levels were more likely to experience peritoneal recurrence and exhibited significantly lower 5-year overall survival rates (39.2% vs. 45.8%, p = 0.039) than did patients displaying low cpDNA levels. Only for late stage (Stages III or IV) gastric cancer, patients harboring cpDNA mutations were more likely to experience vascular invasion (20% vs. 2.4%, p = 0.036) and exhibited a lower 5-year overall survival rate than did those lacking cpDNA mutations (5.6% vs. 31.5%, p = 0.028). High cpDNA levels are associated with peritoneal recurrence and poor prognosis in patients with advanced gastric cancer; harboring cpDNA mutations is associated with poor prognosis among patients with late stage gastric cancer. PMID:26815009

  1. 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.

  2. 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

  3. Complications of Macular Peeling.

    PubMed

    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

  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. 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

  6. Clinical Significance of the Humoral Immune Response to Modified LDL

    PubMed Central

    Lopes-Virella, MF; Virella, G

    2009-01-01

    Human low density lipoprotein (LDL) undergoes oxidation and glycation in vivo. By themselves, oxidized LDL (oxLDL) and AGE-LDL have proinflammatory properties and are considered atherogenic. But the atherogenicity of these lipoproteins are significantly increased as a consequence of the formation of immune complexes (IC) involving autoantibodies spontaneously formed. OxLDL and AGE antibodies have been shown to be predominantly of the IgG1 and IgG3 isotypes. OxLDL antibodies are able to activate the complement system by the classical pathway and to induce FcR-mediated phagocytosis. In vitro and ex vivo studies performed with modified LDL-IC have proven their pro-inflammatory and atherogenic properties. Clinical studies have demonstrated that the levels of circulating modified LDL-IC correlate with parameters indicative of cardiovascular and renal disease in diabetic patients and other patient populations. The possibility that spontaneously formed or induced modified LDL antibodies (particularly IgM oxLDL antibodies) may have a protective effect has been suggested, but the data is unclear and needs to be further investigated. PMID:19427818

  7. The pathogenesis and clinical significance of traumatic subdural hygroma.

    PubMed

    Lee, K S

    1998-07-01

    Subdural hygroma (SDG) is a common post-traumatic lesion. Despite its common occurrence, the pathogenesis and clinical significance are uncertain. The author reviewed the literature to clarify the present knowledge on the pathogenic, diagnostic and therapeutic aspects of this controversial lesion. A trivial trauma can cause a separation of the dura-arachnoid interface, which is the basic requirement for the development of a SDG. If the brain shrinks due to brain atrophy, excessive dehydration or decreased intracranial pressure, fluid collection may develop by a passive effusion. Most SDGs resolve when the brain is well expanded. However, a few SDGs become chronic subdural haematomas, when the necessary conditions persist over several weeks. Since the majority of patients with a SDG do not show a mass effect, surgery is rarely required. Outcome is closely related to the primary head injury not to the SDG itself. The complexity of SDG depends on various factors including the dynamics of absorption and expansion, duration of observation, and indication and rate of surgery, besides variety of the primary head injury in types and severity. SDG is a common epiphenomenon of head injury. PMID:9653522

  8. 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. PMID:27215009

  9. No Clinically Significant Association Between CFH and ARMS2 Genotypes and Response to Nutritional Supplements

    PubMed Central

    Chew, Emily Y.; Klein, Michael L.; Clemons, Traci E.; Agrón, Elvira; Ratnapriya, Rinki; Edwards, Albert O.; Fritsche, Lars G.; Swaroop, Anand; Abecasis, Gonçalo R.

    2014-01-01

    Objective To determine whether genotypes at two major loci associated with late age-related macular degeneration (AMD), complement factor H (CFH) and Age-Related Maculopathy Susceptibility 2 (ARMS2), influenced the relative benefits of Age-Related Eye Disease Study (AREDS) supplements. Design Unplanned retrospective evaluation of a prospective, randomized, placebo-controlled clinical trial of vitamins and minerals for the treatment of AMD. Subjects AREDS participants (mean age of 69 years) who were at risk for developing late AMD and who were randomized to the 4 arms of the AREDS supplements. Methods Analyses were performed using the Cox proportional hazards model to predict progression to late AMD (neovascular or central geographic atrophy). Statistical models, adjusted for age, gender, smoking status and baseline AMD severity, were used to examine the influence of genotypes on the response to therapy with 4 randomly assigned arms of AREDS supplement components: placebo, antioxidants (vitamins C, E, beta-carotene), zinc with copper, or the combination. Main Outcome Measures The influence of the genotype on the relative treatment response to the randomized components of the AREDS supplement, measured as progression to late AMD. Results Of the 1237 genotyped AREDS participants of Caucasian ethnicity, 385 (31.1%) developed late AMD during the mean follow-up period of 6.6 years. As previously demonstrated, both CFH genotype (p=0.005), ARMS2 (<0.0001) and supplement were each individually associated with progression to late AMD. An interaction analysis found no evidence that the relative benefits of AREDS supplementation varied by genotype. Analysis of (1) CFH rs1061170 and rs1410996 combined with ARMS2 rs10490924, with the 4 randomly assigned arms of AREDS supplement and (2) analysis of the combination of CFH rs412852 and rs3766405 with ARMS2 c.372_815del443ins54 with the AREDS components resulted in no interaction (p=0.06 and p=0.45, respectively, before multiplicity

  10. Acute chorioamnionitis and funisitis: definition, pathologic features, and clinical significance.

    PubMed

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

    2015-10-01

    -term complications (ie, sterile inflammation in fetuses, 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 disease. Illustrations of the lesions and diagrams of the mechanisms of disease are provided. PMID:26428501

  11. Laser therapy and macular degeneration

    NASA Astrophysics Data System (ADS)

    Menchini, Ugo; Virgili, Gianni; Giansanti, Fabrizio; Giacomelli, Giovanni; Cappelli, Stefania

    2001-10-01

    Among macular diseases, choroidal neovascularization (CNV) is one of the most common causes of visual loss, especially in the form associated with age-related macular degeneration and pathologic myopia. Research on these diseases has recently evaluated new treatment modalities that use laser light differently; among these, photodynamic therapy (PDT) has been introduced in the clinical practice, allowing us to expand the possibility of reducing visual loss in patients affected by CNV. With PDT, a photosensitizer (verteporfin, VisudyneTM) is injected intravenously, and it selectively binds to new vessels; low-power laser light exposure then activates the drug, leading to oxidative damage of the endothelium and new vessels thrombosis. Yet, other therapies, such as transpupillary termotherapy, or the use of photocoagulation to cause feeder-vessel occlusion, could proof effective, but they need further investigation.

  12. The Clinical Significance of Optimality Theory for Phonological Disorders

    ERIC Educational Resources Information Center

    Gierut, Judith A.; Morrisette, Michele L.

    2005-01-01

    Linguistic theory has made important contributions to the clinical assessment and treatment of children with functional phonological disorders. In this article, Optimality Theory (OT) is introduced as a new linguistic model of grammar. Basic assumptions of the model are described and extended to clinical assessment and treatment. The aim is (1) to…

  13. 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. PMID:25994161

  14. 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

  15. Athletic Training Students' Perception of Significant Clinical Instructor Demographic Characteristics

    ERIC Educational Resources Information Center

    Mulholland, Carlen; Martin, Malissa

    2010-01-01

    Context: Characteristics of a model clinical instructor (CI) continue to be defined. However, certain characteristics are still unknown. Objective: To more fully define and describe quality clinical instruction by examining the impact of employment status, years of experience as a certified athletic trainer (AT), and employment setting on athletic…

  16. [Clinical significance of urinary enzymes in diabetes mellitus].

    PubMed

    Morita, E; Kaizu, K; Uriu, K; Eto, S

    1990-06-01

    The aim of this study was to clarify the clinical significance of urinary enzyme activity in patients with diabetes mellitus. Patients were divided into two groups: group A - 102 outpatients, group B-23 inpatients. Spot urine samples before breakfast from group A and aliquots of 24-hours urine collections at 4 degrees C from group B were used. Urinary enzyme activities (N-acetyl- beta-D-glucosaminidase: NAG, alkaline phosphatase: ALP, leucine aminopeptidase: LAP, gamma-glutamyl transpeptidase: gamma-GTP) were determined by spectrophotometric assay, rate assay, Tuppy method and Orlowski method, respectively. 1) In group A, the percentage of the cases which showed higher than the normal range (NAG: 1.3-8.7, ALP: 4.2-17.7, LAP: 0-22.9 U/g. cer.) was 42.2% in NAG, 21.6% in ALP, and 8.8% in LAP. In a multiple regression analysis, the predictor variables which contributed to NAG were HbA1c, age, urinary protein and the one that contributed to ALP, LAP, gamma-GTP was urinary beta 2-microglobulin. 2) In group B, 87% of NAG was above the normal range (Mean +/- 2 SD; 4.8 +/- 3.9 U/day). There was no difference in the NAG activity between patients with and without nephropathy. The percent of high activities of ALP, LAP and gamma-GTP were 17%, 17%, 4%, respectively. Most of them were patients with nephropathy. There were correlations among ALP, LAP and gamma-GTP, though no correlation existed between NAG and the other three enzymes. These results suggested: 1) NAG reflects lysosomal dysfunction of both glomerular and proximal tubular epithelial cells which may be caused by poor glycemic control.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1975116

  17. TRP channels and temperature in airway disease—clinical significance

    PubMed Central

    Millqvist, Eva

    2015-01-01

    Temperatures above and below what is generally regarded as “comfortable” for the human being have long been known to induce various airway symptoms, especially in combination with exercise in cold climate with temperatures below 0°C, which is naturally since exercise is followed by enhanced ventilation and thus greater amounts of inhaled cold air. The aim was to highlight the knowledge we have today on symptoms from the airways (here also including the eyes) arisen from various temperatures; the mechanisms, the pathophysiology and their clinical significance. The most common eye and airway conditions related to temperature changes are dry eye disease, rhinitis, laryngeal dysfunction, asthma, chronic obstructive pulmonary disease and chronic cough. Transient receptor potential (TRP) ion channels are probably involved in all temperature induced airway symptoms but via different pathways, which are now beginning to be mapped out. In asthma, the most persuasive hypothesis today is that cold-induced asthmatic bronchoconstriction is induced by dehydration of the airway mucosa, from which it follows that provocations with osmotic stimuli like hypertonic saline and mannitol can be used as a surrogate for exercise provocation as well as dry air inhalation. In chronic unexplained cough there seems to be a direct influence of cold air on the TRP ion channels followed by coughing and increased cough sensitivity to inhaled capsaicin. Revelations in the last decades of the ability of several airway TRP ion channels to sense and react to ambient air temperature have opened new windows for the understanding of the pathogenesis in a diversity of airway reactions appearing in many common respiratory diseases. PMID:27227021

  18. 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. PMID:25796101

  19. TRP channels and temperature in airway disease-clinical significance.

    PubMed

    Millqvist, Eva

    2015-01-01

    Temperatures above and below what is generally regarded as "comfortable" for the human being have long been known to induce various airway symptoms, especially in combination with exercise in cold climate with temperatures below 0°C, which is naturally since exercise is followed by enhanced ventilation and thus greater amounts of inhaled cold air. The aim was to highlight the knowledge we have today on symptoms from the airways (here also including the eyes) arisen from various temperatures; the mechanisms, the pathophysiology and their clinical significance. The most common eye and airway conditions related to temperature changes are dry eye disease, rhinitis, laryngeal dysfunction, asthma, chronic obstructive pulmonary disease and chronic cough. Transient receptor potential (TRP) ion channels are probably involved in all temperature induced airway symptoms but via different pathways, which are now beginning to be mapped out. In asthma, the most persuasive hypothesis today is that cold-induced asthmatic bronchoconstriction is induced by dehydration of the airway mucosa, from which it follows that provocations with osmotic stimuli like hypertonic saline and mannitol can be used as a surrogate for exercise provocation as well as dry air inhalation. In chronic unexplained cough there seems to be a direct influence of cold air on the TRP ion channels followed by coughing and increased cough sensitivity to inhaled capsaicin. Revelations in the last decades of the ability of several airway TRP ion channels to sense and react to ambient air temperature have opened new windows for the understanding of the pathogenesis in a diversity of airway reactions appearing in many common respiratory diseases. PMID:27227021

  20. Distress Screening in a Multidisciplinary Lung Cancer Clinic: Prevalence and Predictors of Clinically-Significant Distress

    PubMed Central

    Graves, Kristi D.; Arnold, Susanne M.; Love, Celia L.; Kirsh, Kenneth L.; Moore, Pamela G.; Passik, Steven D.

    2007-01-01

    Summary Screening for distress in cancer patients is recommended by the National Comprehensive Cancer Network, and a Distress Thermometer has previously been developed and empirically-validated for this purpose. The present study sought to determine the rates and predictors of distress in a sample of patients being seen in a multidisciplinary lung cancer clinic. Consecutive patients (N = 333) were recruited from an outpatient multidisciplinary lung cancer clinic to complete the Distress Thermometer, an associated Problem Symptom List, and two questions about interest in receiving help for symptoms. Over half (61.6%) of patients reported distress at a clinically significant level, and 22.5% of patients indicated interest in receiving help with their distress and/or symptoms. Problems in the areas of family relationships, emotional functioning, lack of information about diagnosis/treatment, physical functioning, and cognitive functioning were associated with higher reports of distress. Specific symptoms of depression, anxiety, pain and fatigue were most predictive of distress. Younger age was also associated with higher levels of distress. Distress was not associated with other clinical variables, including stage of illness or medical treatment approach. Similar results were obtained when individuals who had not yet received a definitive diagnosis of lung cancer (n = 134) were excluded from analyses; however, family problems and anxiety were no longer predictive of distress. Screening for distress in a multidisciplinary lung cancer clinic is feasible and a significant number of patients can be expected to meet clinical criteria for distress. Results also highlight younger age and specific physical and psychosocial symptoms as predictive of clinically-significant distress. Identification of the presence and predictors of distress are the first steps toward appropriate referral and treatment of symptoms and problems that contribute to cancer patients’ distress. PMID

  1. 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

  2. [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. PMID:25715554

  3. The detection of clinically significant erythrocyte alloantibodies using a human mononuclear phagocyte assay

    SciTech Connect

    Schanfield, M.S.; Stevens, J.O.; Bauman, D.

    1981-01-01

    Red blood cell (RBC) allo- or autoantibodies, which markedly reduce the survival of transfused or autologous RBC, are considered to be clinically significant antibodies. The occurrence of antibodies against high-incidence antigens, which are occasionally associated with clinically significant RBC destruction or are of unknown clinical significance, often creates delays in providing blood to patients. In the majority of cases these antibodies are benign; however, clinically significant examples of these antibodies have been reported. An in vitro homologous human mononuclear phagocyte assay (MPA) was used to study antibodies directed against specificities associated with variable clinical significance. Two antibodies reported to be clinically significant and 25 antibodies known to be clinically insignificant were tested by MPA. The results indicate that clinically significant antibodies have a significantly higher score than do clinically insignificant antibodies, with no overlap observed between the two groups. An additional eight antibodies with unknown clinical significance were tested. None of these antibodies had scores in the clinically significant range.

  4. 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.

  5. Clinical Significance of Microbial Infection and Adaptation in Cystic Fibrosis

    PubMed Central

    Hauser, Alan R.; Jain, Manu; Bar-Meir, Maskit; McColley, Susanna A.

    2011-01-01

    Summary: A select group of microorganisms inhabit the airways of individuals with cystic fibrosis. Once established within the pulmonary environment in these patients, many of these microbes adapt by altering aspects of their structure and physiology. Some of these microbes and adaptations are associated with more rapid deterioration in lung function and overall clinical status, whereas others appear to have little effect. Here we review current evidence supporting or refuting a role for the different microbes and their adaptations in contributing to poor clinical outcomes in cystic fibrosis. PMID:21233507

  6. Applications of the psychotherapy phase model to clinically significant deterioration.

    PubMed

    Swift, Joshua K; Callahan, Jennifer L; Heath, Christopher J; Herbert, Gregory L; Levine, Jason C

    2010-06-01

    While previous research on deterioration has focused on identifying individuals at risk for negative outcomes, little is known about the nature or pattern by which deterioration occurs. The problem of deterioration is especially salient in training clinics; a setting in which higher deterioration rates have been reported. Two studies were designed to test the applicability of the phase model to deterioration in a training clinic and to replicate the model with a training clinic referral-base sample. In Study 1, the course of therapy was monitored for 135 clients. For the 38 clients who deteriorated during therapy, a model where increased symptoms (demediation) reliably preceded both decreased functioning (dehabilitation) and decreased well-being (demoralization) was found. In Study 2, the same three phases were prospectively monitored for 914 undergraduate students on a weekly basis throughout a single semester. For the 158 individuals who deteriorated during this time, a model where demediation reliably preceded dehabilitation, which preceded demoralization was found. These results have clinical implications for the use of tailored intervention strategies focusing on the deterioration phases. PMID:22402050

  7. The significance of coronary reserve in clinical heart disease.

    PubMed

    Strauer, B E

    1990-03-15

    The clinical syndrome "coronary insufficiency with normal coronary arteriogram" is found in approximately 10% to 20% of patients with exercise-induced coronary insufficiency. In most of these cases, disturbances of the coronary microcirculation are present. They can appear in vascular diseases (arterial hypertension, systemic immunopathies, immune complex vasculitis), in rheologic diseases (paraproteinemia, hyperlipoproteinemia, polyglobulia) and in disturbances of transport and diffusion of oxygen (carbon monoxide intoxication, methemoglobinemia). The clinical diagnosis is based on the usual diagnostic procedures (electrocardiogram, exercise electrocardiogram, responsiveness to nitroglycerin), as well as on newer functionally oriented diagnostic procedures (determinations of coronary blood flow and coronary vascular reserve, production of lactate, serologic findings, histology and immune histology of peripheral arteries, measurements of viscosities in both plasma and blood). Many clinically relevant disturbances in the coronary microcirculation can thus be detected and treated on a rational basis by management of the underlying main disease, that is, by treatment of the vascular, rheologic and metabolic disorders. Persistent angina pectoris in the presence of a normal coronary arteriogram does not represent an end to coronary diagnostic procedures, but introduces the clinical task of using all diagnostic possibilities to enable functional and therapeutic assessment of the coronary microcirculation. PMID:2307786

  8. Clinical significance of microembolus detection by transcranial Doppler sonography in cardiovascular clinical conditions.

    PubMed

    Hudorović, Narcis

    2006-01-01

    Transcranial Doppler can detect microembolic signals, which are characterized by unidirectional high intensity increase, short duration, and random occurrence, producing a "whistling" sound. Microembolic signals have been proven to represent solid or gaseous particles within the blood flow. Microemboli have been detected in a number of clinical cardiovascular settings: carotid artery stenosis, aortic arch plaques, atrial fibrillation, myocardial infarction, prosthetic heart valves, patent foramen ovale, valvular stenosis, during invasive procedures (angiography, percutaneous transluminal angioplasty) and surgery (carotid, cardiopulmonary bypass). Despite numerous studies performed so far, clinical significance of microembolic signals is still unclear. This article provides an overview of the development and current state of technical and clinical aspects of microembolus detection. PMID:17462357

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

    PubMed Central

    Mantel, Irmela

    2015-01-01

    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

  10. Treatment-resistant panic disorder: clinical significance, concept and management.

    PubMed

    Chen, Mu-Hong; Tsai, Shih-Jen

    2016-10-01

    Panic disorder is commonly prevalent in the population, but the treatment response for panic disorder in clinical practice is much less effective than that in our imagination. Increasing evidence suggested existence of a chronic or remitting-relapsing clinical course in panic disorder. In this systematic review, we re-examine the definition of treatment-resistant panic disorder, and present the potential risk factors related to the treatment resistance, including the characteristics of panic disorder, other psychiatric and physical comorbidities, and psychosocial stresses. Furthermore, we summarize the potential pathophysiologies, such as genetic susceptibility, altered brain functioning, brain-derived neurotrophic factor, and long-term inflammation, to explain the treatment resistance. Finally, we conclude the current therapeutic strategies for treating treatment-resistant panic disorder from pharmacological and non-pharmacological views. PMID:26850787

  11. Molecular Analysis and Clinical Significance of Lactobacillus spp. Recovered from Clinical Specimens Presumptively Associated with Disease

    PubMed Central

    Martinez, Raquel M.; Hulten, Kristina G.; Bui, Uyen

    2014-01-01

    Lactobacillus spp. are part of the normal human flora and are generally assumed to be nonpathogenic. We determined the genotypic identification of >100 Lactobacillus isolates from clinical specimens in the context of presumed pathogenic potential (e.g., recovered as the single/predominant isolate from a sterile site or at ≥105 CFU/ml from urine). This study assessed the clinical significance and the frequency of occurrence of each Lactobacillus sp. We identified 16 species of Lactobacillus by 16S rRNA gene sequence analysis, 10 of which could not be associated with disease. While Lactobacillus rhamnosus, Lactobacillus gasseri, and Lactobacillus paracasei were associated with infections, L. gasseri was also a common colonizing/contaminating species. Lactobacillus casei, Lactobacillus johnsonii, and Lactobacillus delbrueckii were associated with at least one infection. Species commonly used in probiotic products (e.g., L. rhamnosus and L. casei) were identical, by 16S rRNA gene sequencing, to our isolates associated with disease. Human isolates of Lactobacillus spp. have differing site associations and levels of clinical significance. Knowing the niche and pathogenic potential of each Lactobacillus sp. can be of importance to both clinical microbiology and the food and probiotic supplement industry. PMID:24131686

  12. An exploration of comorbid symptoms and clinical correlates of clinically significant hoarding symptoms

    PubMed Central

    Hall, Brian J.; Tolin, David F.; Frost, Randy O.; Steketee, Gail

    2016-01-01

    Background Hoarding Disorder is currently being considered for inclusion in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, yet remains poorly understood. Consensus is building that hoarding may constitute a separate disorder, although comorbidity remains high and complicates the diagnostic picture. The purpose of this investigation was to explore patterns of comorbidity among people who engage in hoarding behavior in order to better understand its clinical presentation and phenomenology. Methods Data were collected from a large internet sample (N = 363) of people who self-identified as having hoarding problems, met criteria for clinically significant hoarding, and completed all measures for this study. Participants self-reported their symptoms of disorders commonly co-occurring with hoarding (obsessive compulsive disorder [OCD], depression, and attention deficit hyperactivity disorder [ADHD]), along with other clinical problems. Results: Latent class analysis results indicated that the participants were grouped into three classes: “non-comorbid” hoarding (42%), hoarding with depression (42%), and hoarding with depression and inattention (16%). Conclusions Depression symptoms were the most commonly co-occurring symptom in this sample. Contrary to previous theory relating to hoarding etiology, OCD symptoms were not significantly co-occurring and a large percentage of the study participants were free from comorbid symptoms of OCD, depression, and ADHD. This suggests that hoarding disorder is not primarily the consequence of other psychiatric conditions. Implications for DSM-5, clinical treatment, and future research directions are discussed. PMID:23213052

  13. [Persistent primitive trigeminal artery: critical review of the clinical significance].

    PubMed

    Oliveira, H A; Passos, J D; Barbosa, M B; Do Amorim, E A

    1991-09-01

    The authors report three cases of persistence of primitive trigeminal artery with no evidence of a relationship between its presence and any specific clinical syndrome. They discuss embryological aspects and establish the correlation between the presence of this malformation and other intracranial pathologies, such as "tic douloureux" and morphologic alteration of the circle of Willis. A critical review of the literature is also presented. PMID:1807233

  14. The clinical significance and management of microleakage. Part one.

    PubMed

    Larson, Thomas D

    2005-01-01

    This research reviews relevant articles related to microleakage from 1966 to the present. The review discusses what the sensation of microleakage is clinically; how dentin permeability is related to microleakage; how the quality of dentin affects permeability and microleakage; what the effects of bacterial infiltration from microleakage can be, as well as the body's defenses against bacterial infiltration within the tooth complex; how caries and microleakage are related; and how various materials and procedures can be used to limit microleakage. PMID:15807140

  15. 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

  16. 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

  17. 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. PMID:25716450

  18. Clinical significance of treatment delay in status epilepticus

    PubMed Central

    2013-01-01

    Background Status epilepticus (SE) is a medical emergency that requires immediate action. The clinical and demographic features of SE are known to be highly variable. The objective of this study was to analyze the effect of treatment delays on patient recovery and different clinical factors that are important in the determination of the acute prognosis in SE. Methods This population-based study included 109 consecutive visits of patients with the diagnosis of SE in the emergency department (ED) of Tampere University Hospital. The clinical features of SE were compared with the discharge condition. Results The treatment delays were long; in half of the patients, the delay for paramedic arrival was over 30 min, and in one-third of the cases, the delay was over 24 h. ED patients who had less than 1 h of delay before the administration of an antiepileptic drug (AED) had better outcomes compared to patients with a greater than 1 h delay (p < 0.05). The two major etiologies for the SE were cerebrovascular disease and alcohol misuse. A good immediate outcome was found in 46% of the patients. Epileptiform activity on the EEG, a history of epilepsy or SE, presence of cardiovascular disease, and alcohol misuse were associated with a poor outcome. Conclusions The results of this study emphasize the importance of an urgent response by emergency services and proper recognition of atypical phenotypes of SE. PMID:23445821

  19. Outcomes of pharmacological management of nocturia with non-antidiuretic agents: does statistically significant equal clinically significant?

    PubMed

    Smith, Ariana L; Wein, Alan J

    2011-05-01

    To evaluate the statistical and clinical efficacy of the pharmacological treatments of nocturia using non-antidiuretic agents. A literature review of treatments of nocturia specifically addressing the impact of alpha blockers, 5-alpha reductase inhibitors (5ARI) and antimuscarinics on reduction in nocturnal voids. Despite commonly reported statistically significant results, nocturia has shown a poor clinical response to traditional therapies for benign prostatic hyperplasia including alpha blockers and 5ARI. Similarly, nocturia has shown a poor clinical response to traditional therapies for overactive bladder including antimuscarinics. Statistical success has been achieved in some groups with a variety of alpha blockers and antimuscarinic agents, but the clinical significance of these changes is doubtful. It is likely that other types of therapy will need to be employed in order to achieve a clinically significant reduction in nocturia. PMID:21518417

  20. The clinical significance and management of microleakage. Part two.

    PubMed

    Larson, Thomas D

    2005-01-01

    This research reviews relevant articles related to microleakage from 1966 to the present. The review discusses what the sensation of microleakage is clinically; how dentin permeability is related to microleakage; how the quality of dentin affects permeability and microleakage; what the effects of bacterial infiltration from microleakage can be, as well as the body's defenses against bacterial infiltration within the tooth complex; how caries and microleakage are related; and how various materials and procedures can be used to limit microleakage. Part Two reviews the use of materials, technique, and procedures to limit microleakage, and specifically how the use of various dentin and enamel bonding materials can be used to limit microleakage. PMID:15934228

  1. 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

  2. Anticoagulative strategies in reconstructive surgery – clinical significance and applicability

    PubMed Central

    Jokuszies, Andreas; Herold, Christian; Niederbichler, Andreas D.; Vogt, Peter M.

    2012-01-01

    Advanced strategies in reconstructive microsurgery and especially free tissue transfer with advanced microvascular techniques have been routinely applied and continously refined for more than three decades in day-to-day clinical work. Bearing in mind the success rates of more than 95%, the value of these techniques in patient care and comfort (one-step reconstruction of even the most complex tissue defects) cannot be underestimated. However, anticoagulative protocols and practices are far from general acceptance and – most importantly – lack the benchmark of evidence basis while the reconstructive and microsurgical methods are mostly standardized. Therefore, the aim of our work was to review the actual literature and synoptically lay out the mechanisms of action of the plethora of anticoagulative substances. The pharmacologic prevention and the surgical intervention of thrombembolic events represent an established and essential part of microsurgery. The high success rates of microvascular free tissue transfer as of today are due to treatment of patients in reconstructive centers where proper patient selection, excellent microsurgical technique, tissue transfer to adequate recipient vessels, and early anastomotic revision in case of thrombosis is provided. Whether the choice of antithrombotic agents is a factor of success remains still unclear. Undoubtedly however the lack of microsurgical experience and bad technique can never be compensated by any regimen of antithrombotic therapy. All the more, the development of consistent standards and algorithms in reconstructive microsurgery is absolutely essential to optimize clinical outcomes and increase multicentric and international comparability of postoperative results and complications. PMID:22294976

  3. Brain death in ICU patients: Clinical significance of endocrine changes

    PubMed Central

    Bajwa, Sukhminder Jit Singh; Haldar, Rudrashish

    2014-01-01

    Numerous studies have been carried out among patients admitted in intensive care unit (ICU) having primary endocrine pathology, endocrine manifestations of systemic diseases or post-endocrine tissue surgery. However, minimal literary evidence is available highlighting the endocrine changes occurring during brain death in critically ill patients. A precise and timely diagnosis of brain death is required to convey the relatives about the prognosis and also to possibly plan for organ retrieval for transplantation purposes. The diagnosis of this condition as of today remains largely a clinical one. Brain death is associated with a multitude of endocrinological alterations which are yet to be completely unraveled and understood. Evaluating these endocrinological modifications lends us an added vista to add to the existing clinical parameters which might help us to confirm the diagnosis of brain death with a higher degree of precision. Moreover, since the efficacy of hormone replacement therapy to benefit in organ retrieval remains yet unproven, newer diagnostic modalities and research studies are definitely called for to strategize the optimal dosage and duration of such therapies. PMID:24741523

  4. Determination of serum lipid profile in patients with diabetic macular edema that referred to Shahid Beheshti and Ayatollah Rouhani Hospitals, Babol during 2011-2012

    PubMed Central

    Rasoulinejad, Seyed Ahmad; Iri, Habib-Ollah

    2015-01-01

    Background: Diabetes is a common metabolic disorder leading to the development of many complications, among which diabetic retinopathy and macular edema are the most significant. These complications can contribute to blindness if not diagnosed or treated properly, and several studies have been conducted to evaluate the methods for the prevention or slowing down their progression. Therefore, serum lipids, apparently play an effective role in the creation and acceleration of macular edema, we therefore determined the relationship of serum lipid level in patients with diabetic macular edema in the present study. Methods: 180 participants were selected from patients with the definite diagnosis of diabetes referred to the eye clinic of Shahid Beheshti and Ayatollah Rouhani Hospitals of Babol during 2011-2012, the patients with a history of taking lipid –lowering drugs and hypertension were excluded from the study. The study data were provided from the medical records of each patients. SPSS Version 18 was used for analyses. Results: In the present investigation, the mean age of participants was 53.22±with the age range of 18-77 years. Ninety patients with diabetic retinopathy and macular edema were compared with ninety patients with diabetic retinopathy without macular edema (control group) were compared. There was a significant difference in serum cholesterol and LDL-cholesterol between patients and groups (p<0.000). Conclusion: The results of this study indicate that high serum cholesterol and LDL-cholesterol is associated with severity of diabetic retinopathy particularly with macular edema PMID:26221504

  5. Clinical significance of multi-leaf collimator calibration errors.

    PubMed

    Norvill, Craig; Jenetsky, Guy

    2016-03-01

    This planning study investigates the clinical impact of multi-leaf collimator (MLC) calibration errors on three common treatment sites; head and neck (H&N), prostate and stereotactic body radiotherapy (SBRT) for lung. All plans used using either volumetric modulated adaptive therapy or dynamic MLC techniques. Five patient plans were retrospectively selected from each treatment site, and MLC errors intentionally introduced. MLC errors of 0.7, 0.4 and 0.2 mm were sufficient to cause major violations in the PTV planning criteria for the H&N, prostate and SBRT lung plans. Mean PTV dose followed a linear trend with MLC error, increasing at rates of 3.2-5.9 % per millimeter depending on treatment site. The results indicate that an MLC quality assurance program that provides sub-millimeter accuracy is an important component of intensity modulated radiotherapy delivery techniques. PMID:26819078

  6. 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

  7. The significance of Candida pulcherrima findings in human clinical specimens.

    PubMed

    Pospisil, L

    1989-11-01

    From 1971 to 1976 the author examined by cultivation on Sabouraud glucose agar, 1720 specimens of the most varied materials--skin scales, nails, hair, beard, sputum--obtained from patients suffering from skin problems. In no one single case did he find Candida pulcherrima. However, since 1977 he has found C. pulcherrima to be on an increase. From 1977 to 1984 in 4644 specimens C. pulcherrima was found in 44 cases. 38 strains, i.e. 86%, were isolated from patients with clinical diagnosis of mycotic infection. The most frequent diagnosis was onychomycosis, 36%. Cultivation findings were mostly profuse and massive relative to the number of germs, in some patients even occurring repeatedly. In view of these findings it may be necessary to revise the views purporting the finding of C. pulcherrima from human material to be insignificant. PMID:2615783

  8. Studies in the radiobiology of osteoradionecrosis and their clinical significance

    SciTech Connect

    Marx, R.E.; Johnson, R.P.

    1987-10-01

    The radiobiology of osteoradionecrosis is a complex of cellular death and cellular functional impairments from radiation energy transfers. Four studies of irradiated patients and a data base from 536 patients with osteoradionecrosis revealed separate pathophysiologic conditions for osteoradionecrosis induced by early trauma, osteoradionecrosis induced by late trauma, and spontaneous osteoradionecrosis. A large body of data suggested useful clinical guidelines for the management of irradiated patients. The guidelines, in part, include a recommendation for deferring radiation treatment for 21 days after tissue wounding, if possible; a relative contraindication to wounding tissue during a radiation course; a recommendation for the use of hyperbaric oxygen before wounding; and a strong recommendation to provide comprehensive dental care to the irradiated patient.

  9. Adverse effects of acupuncture. Which are clinically significant?

    PubMed Central

    Chung, Ainee; Bui, Luke; Mills, Edward

    2003-01-01

    OBJECTIVE: To review potentially serious adverse events associated with acupuncture. QUALITY OF EVIDENCE: Studies in the medical literature primarily provide level II evidence from retrospective reviews, case reports, and prospective surveys of practitioners. MAIN MESSAGE: Both the general public and physicians are becoming more interested in the ancient Chinese medical practice of acupuncture. This paper discusses the basic philosophy of acupuncture and describes adverse events that might be associated with acupuncture treatment. Some events, such as nausea and syncope, can be mild and transient, but rare events, such as septicemia and hepatitis C infection, can be fatal. As the role of acupuncture in today's multidisciplinary clinics increases, the complications of acupuncture, although infrequent, cannot be overlooked. CONCLUSION: Responsible clinicians practising acupuncture and seeing patients who use acupuncture should be aware of the adverse events associated with it. PMID:12943357

  10. Predictors of treatment attrition among an outpatient clinic sample of youths with clinically significant anxiety.

    PubMed

    Gonzalez, Araceli; Weersing, V Robin; Warnick, Erin M; Scahill, Lawrence D; Woolston, Joseph L

    2011-09-01

    Predictors of treatment attrition were examined in a sample of 197 youths (ages 5-18) with clinically-significant symptoms of anxiety seeking psychotherapy services at a community-based outpatient mental health clinic (OMHC). Two related definitions of attrition were considered: (a) clinician-rated dropout (CR), and (b) CR dropout qualified by phase of treatment (pre, early, or late phases) (PT). Across both definitions, rates of attrition in the OMHC sample were higher than those for anxious youths treated in randomized controlled trials, and comorbid depression symptoms predicted dropout, with a higher rate of depressed youths dropping out later in treatment (after 6 sessions). Using the PT definition, minority status also predicted attrition, with more African-American youths lost pre-treatment. Other demographic (age, gender, single parent status) and clinical (externalizing symptoms, anxiety severity) characteristics were not significantly associated with attrition using either definition. Implications for services for anxious youths in public service settings are discussed. Results highlight the important role of comorbid depression in the treatment of anxious youth and the potential value of targeted retention efforts for ethnic minority families early in the treatment process. PMID:20976618

  11. Clinical significance of serum adipokines levels in lung cancer.

    PubMed

    Kerenidi, Theodora; Lada, Martha; Tsaroucha, Agori; Georgoulias, Panagiotis; Mystridou, Parthena; Gourgoulianis, Konstantinos I

    2013-06-01

    Adipokines have a significant effect on metabolism, immunoinflammatory responses as well as on carcinogenesis; therefore, we aimed at evaluating their potential predictive and prognostic significance in lung cancer. Eighty patients--mean age 62.9 ± 9.2 years--with previously untreated lung cancer (61 NSCLC and 19 SCLC) of all stages and 40 healthy individuals were enrolled in this study. Serum levels of leptin, adiponectin and ghrelin were measured using human Radioimmunoassay kits. Serum leptin levels in lung cancer patients were lower compared to control (p < 0.0001), while adiponectin and ghrelin levels were significantly increased in patients (p = 0.0003 and p = 0.0043, respectively). Additionally, the leptin/adiponectin ratio was significantly lower in the patients group compared to controls (p < 0.0001]. There was no association between serum levels of adipokines and any of the patient clinicopathological characteristics or response to therapy. Nevertheless, patients with lower values of serum leptin had shorter overall survival (p = 0.014), whereas multivariate analysis revealed leptin levels as an independent prognostic factor for survival (p = 0.024, HR 0.452, CI 95 % 0.232-0.899). These results suggest that adipokines may play a role in the pathogenesis of lung cancer, while leptin serum levels might provide useful prognostic information. PMID:23430445

  12. Diabetic macular edema: New promising therapies

    PubMed Central

    Shamsi, Hanan N Al; Masaud, Jluwi S; Ghazi, Nicola G

    2013-01-01

    The treatment of diabetic macular edema is rapidly evolving. The era of laser therapy is being quickly replaced by an era of pharmacotherapy. Several pharmacotherapies have been recently developed for the treatment of retinal vascular diseases such as diabetic macular edema. Several intravitreal injections or sustained delivery devices have undergone phase 3 testing while others are currently being evaluated. The results of clinical trials have shown the superiority of some of these agents to laser therapy. However, with the availability of several of these newer agents, it may be difficult to individualize treatment options especially those patients respond differently to various therapies. As such, more effort is still needed in order to determine the best treatment regimen for a given patient. In this article, we briefly summarize the major new therapeutic additions for the treatment of diabetic macular edema and allude to some future promising therapies. PMID:24379924

  13. Bruch's membrane diffusivity for vascular endothelial growth factors may explain variable response to wet age-related macular degeneration treatment: clinical implications.

    PubMed

    Peddada, Ram R

    2014-12-01

    The hypothesis presented is that diffusivity of vascular endothelial growth factors (VEGF) across Bruch's membrane is an important parameter that distinguishes prompt and slow responders to anti-VEGF treatment in wet age-related macular degeneration (AMD). Accordingly, slow-responders have a high diffusivity and will attain peak VEGF levels on the choroidal side of Bruch's membrane rapidly, probably before or around the time of the next monthly anti-VEGF injection. If a fixed dose of anti-VEGF is used at each monthly treatment (as is the current practice), depending on the initial level of VEGF at that time of injection, VEGF with each treatment will vary. Therefore, diffusion will occur at a different concentration gradient in each treatment cycle subsequent to the injection. Hence, by Fick's Second Law of Diffusion, the slope of the concentration versus time curve for each treatment cycle will be different from the preceding cycle. This leads to a different peak concentration just prior to the next monthly injection. So, when a fixed dose of the anti-VEGF is used at each monthly treatment peak VEGF level fluctuates instead of going down continuously which prolongs the treatment. Thus, doses of anti-VEGF may have to be tapered to decrease the concentration gradient and to slow down the rate of diffusion of VEGF. Diffusivity of Bruch's membrane with regards to VEGF is a simple concept that can explain the variable response to anti-VEGF treatment in wet AMD. If validated through clinical trial the treatment protocol for wet AMD can be more precise and tailored to individual patients. PMID:25468789

  14. 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

  15. Laboratory aspects of clinically significant rapidly growing mycobacteria.

    PubMed

    Set, R; Shastri, J

    2011-01-01

    The pathogenic potential of the rapidly growing mycobacteria (RGM) has started being recognized. This is due to more sensitive and specific techniques in the laboratory. The RGM are generally defined as nontuberculous species of mycobacteria that show visible growth on agar media within 7 days. RGM are widely distributed in nature and have been isolated from natural water, tap water, and soil. Several biochemical tests, high performance liquid chromatography, and molecular techniques have been developed for rapid identification of these species. The American Thoracic Society and the Infectious Disease Society of America recommend that RGM should be identified to the species level using a recognized acceptable methodology such as polymerase chain reaction restriction enzyme analysis or biochemical testing and routine susceptibility testing of RGM should include amikacin, imipenem, doxycycline, the fluorinated quinolones, a sulphonamide or trimethoprim-sulphamethoxazole, cefoxitin, clarithromycin, linezolid, and tobramycin. The diseases caused by these organisms have varied manifestations. They have been responsible for a number of healthcare-associated outbreaks and pseudo-outbreaks. For recognition of outbreaks, it is important to be familiar with the causative organisms like RGM which are most frequently involved in healthcare-associated outbreaks and pseudo outbreaks. It is essential to intervene as soon as possible to interrupt this transmission. Large gaps still exist in our knowledge of RGM. Unquestionably more studies are required. Through this review, we wish to emphasize that reporting of RGM from clinical settings along with their sensitivity patterns is an absolute need of the hour. PMID:22120792

  16. Left-sided gallbladder: Its clinical significance and imaging presentations

    PubMed Central

    Hsu, Sheng-Lung; Chen, Tai-Yi; Huang, Tung-Liang; Sun, Cheuk-Kwan; Concejero, Allan M; Tsang, Leo Leung-Chit; Cheng, Yu-Fan

    2007-01-01

    AIM: To assess the importance of preoperative diagnosis and presentation of left-sided gallbladder using ultrasound (US), CT and angiography. METHODS: Retrospective review of 1482 patients who underwent enhanced CT scanning was performed. Left-sided gallbladder was diagnosed if a right-sided ligamentum teres was present. The image presentations on US, CT and angiography were also reviewed. RESULTS: Left-sided gallbladder was diagnosed in nine patients. The associated abnormalities on CT imaging included portal vein anomalies, absence of umbilical portion of the portal vein in the left lobe of the liver, club-shaped portal vein in the right lobe of the liver, and difficulty in identifying segment IV. Angiography in six of nine patients demonstrated abnormal portal venous system (trifurcation type in four of six patients). The main hepatic arteries followed the portal veins in all six patients. The segment IV artery was identified in four of six patients using angiography, although segment IV was difficult to define on CT imaging. Hepatectomy was performed in three patients with concomitant liver tumor and the diagnosis of left-sided gallbladder was confirmed intraoperatively. CONCLUSION: Left-sided gallbladder is an important clinical entity in hepatectomy due to its associated portal venous and biliary anomalies. It should be considered in US, CT and angiography images that demonstrate no definite segment IV, absence of umbilical portion of the portal vein in the left lobe, and club-shaped right anterior portal vein. PMID:18081230

  17. Variations of Gonadal Veins: Embryological Prospective and Clinical Significance

    PubMed Central

    Gupta, Raman; Aggarwal, Navita

    2015-01-01

    Introduction: An adequate knowledge of anomalies of gonadal veins will help the radiologists and surgeons in recognition and protection of these veins which play major roles in thermo-regulation that is essential for the efficient functioning of testis on which the survival of the human species depends. Aim: The aim of this work is to present an analysis of the anatomical variations of gonadal veins. An effort has also been made to explicate the possible embryological model of development of such variants and to present the variable clinical aspects concerning them. Materials and Methods: Gonadal veins in 60 dissection room cadavers were examined for variations from the classic anatomic description. Result: In the present study, out of 60 cases, male: female ratio was 2:1(40:20) in which no variation was found in ovarian veins. In the 18 (45%) cases, testicular veins showed variations which consist of duplication and atypical drainage. Discussion: Variations of drainage of gonadal vein are due to error of embryological development in venous shift and alteration in anastomotic channel of post-cardinal, supra-cardinal and sub cardinal veins. Conclusion: The gonadal veins present numeric variations as well as variations in its site of drainage, which attributed to the various pathological conditions as varicocele and pelvic congestion syndrome, leading to infertility in patients. Hence, in -depth knowledge of these developmental anomalies of gonadal veins is important. PMID:25859438

  18. Analysis of APC mutation in human ameloblastoma and clinical significance.

    PubMed

    Li, Ning; Liu, Bing; Sui, Chengguang; Jiang, Youhong

    2016-01-01

    As a highly conserved signaling pathway, Wnt/β-catenin signal transduction pathway plays an important role in many processes. Either in the occurrence or development of tumor, activation of this pathway takes an important place. APC inhibits Wnt/β-catenin pathway to regulate cell proliferation and differentiation. This study aimed to investigate the function of cancer suppressor gene. PCR amplification and sequencing method was used to analyze APC mutations of human clinical specimens. The pathological specimens were collected for PCR and clear electrophoretic bands were obtained after electrophoresis. The gene sequence obtained after purification and sequencing analysis was compared with the known APC gene sequence (NM_000038.5). Base mutations at APC 1543 (T → C), APC-4564 (G → A), APC-5353 (T → G), APC-5550 (T → A) and APC-5969 (G → A) locus existed in 22 (27.5 %), 12 (15 %), 5 (6.25 %), 13 (16.25 %) and 12 patients (15 %), respectively. Gene mutations existed in ameloblastoma, and the mutation loci were 1543 locus (T → C), 4564 locus (G → A), 5353 locus (T → G), 5550 locus (T → A) and 5969 locus (G → A) 15 %, respectively. APC mutation plays a certain role in monitoring the tumor malignant degree as it may indicate the transition process of ameloblastoma malignant phenotype. PMID:27065015

  19. 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

  20. Clinical significance of T cell metabolic reprogramming in cancer.

    PubMed

    Herbel, Christoph; Patsoukis, Nikolaos; Bardhan, Kankana; Seth, Pankaj; Weaver, Jessica D; Boussiotis, Vassiliki A

    2016-12-01

    Conversion of normal cells to cancer is accompanied with changes in their metabolism. During this conversion, cell metabolism undergoes a shift from oxidative phosphorylation to aerobic glycolysis, also known as Warburg effect, which is a hallmark for cancer cell metabolism. In cancer cells, glycolysis functions in parallel with the TCA cycle and other metabolic pathways to enhance biosynthetic processes and thus support proliferation and growth. Similar metabolic features are observed in T cells during activation but, in contrast to cancer, metabolic transitions in T cells are part of a physiological process. Currently, there is intense interest in understanding the cause and effect relationship between metabolic reprogramming and T cell differentiation. After the recent success of cancer immunotherapy, the crosstalk between immune system and cancer has come to the forefront of clinical and basic research. One of the key goals is to delineate how metabolic alterations of cancer influence metabolism-regulated function and differentiation of tumor resident T cells and how such effects might be altered by immunotherapy. Here, we review the unique metabolic features of cancer, the implications of cancer metabolism on T cell metabolic reprogramming during antigen encounters, and the translational prospective of harnessing metabolism in cancer and T cells for cancer therapy. PMID:27510264

  1. Diabetic Macular Edema: Options for Adjunct Therapy.

    PubMed

    Calvo, Pilar; Abadia, Beatriz; Ferreras, Antonio; Ruiz-Moreno, Oscar; Verdes, Guayente; Pablo, Luis E

    2015-09-01

    Diabetes mellitus (DM) is a chronic disease that affects 387 million people worldwide. Diabetic retinopathy (DR), a common complication of DM, is the main cause of blindness in the active population. Diabetic macular edema (DME) may occur at any stage of DR, and is characterized by vascular hyperpermeability accompanied by hard exudates within the macula. Medical and surgical therapies have dramatically reduced the progression of DR, and timely intervention can reduce the risk of severe vision loss by more than 90 %. In 2012, intravitreal ranibizumab became the first antivascular endothelial growth factor (anti-VEGF) agent approved for DME and, since then, many reports of the use of ranibizumab for DME have been promising. Randomized, prospective, multicenter clinical trials-most notably, RESOLVE, READ-2, RISE/RIDE, RESTORE, DRCR.net protocol I, and RETAIN-reported improvements in best-corrected visual acuity and decreased central retinal thickness as measured with optical coherence tomography in patients with DME. Similar treatment benefits have also been noted in clinical trials evaluating intravitreal aflibercept and bevacizumab (DAVINCI, VISTA/VIVID, and BOLT) and more recently DRCR.net protocol T. Intravitreal steroids (dexamethasone intravitreal implant and fluocinolone acetonide), particularly in refractory cases, also play a significant role in the management of DME (MEAD/CHAMPLAIN and FAMOUS/FAME studies). In summary, over the last 5 years, blocking VEGF and inflammation has been shown to improve visual outcomes in patients with macular edema due to DM, revolutionizing the treatment of center-involved DME and establishing a new standard of care. PMID:26242766

  2. Clinical significance of lactate in acute cardiac patients

    PubMed Central

    Lazzeri, Chiara; Valente, Serafina; Chiostri, Marco; Gensini, Gian Franco

    2015-01-01

    Lactate, as a metabolite of easy and quick assessment, has been studied over time in critically ill patients in order to evaluate its prognostic ability. The present review is focused on the prognostic role of lactate levels in acute cardiac patients (that is with acute coronary syndrome, cardiogenic shock, cardiac arrest, non including post cardiac surgery patients). In patients with ST-elevation myocardial infarction treated with mechanical revascularization, hyperlactatemia identified a subset of patients at higher risk for early death and in-hospital complications, being strictly related mainly to hemodynamic derangement. The prognostic impact of hyperlactatemia on mortality has been documented in patients with cardiogenic shock and in those with cardiac arrest even if there is no cut-off value of lactate to be associated with worse outcome or to guide resuscitation or hemodynamic management. Therapeutic hypothermia seems to affect per se lactate values which have been shown to progressively decrease during hypothermia. The mechanism(s) accounting for lactate levels during hypothemia seem to be multiple ranging from the metabolic effects of reduced temperatures to the hemodynamic effects of hypothermia (i.e., reduced need of vasopressor agents). Serial lactate measurements over time, or lactate clearance, have been reported to be clinically more reliable than lactate absolute value also in acute cardiac patients. Despite differences in study design, timing of lactate measurements and type of acute cardiac conditions (i.e., cardiogenic shock, cardiac arrest, refractory cardiac arrest), available evidence strongly suggests that higher lactate levels can be observed on admission in non-survivors and that higher lactate clearance is associated with better outcome. PMID:26322188

  3. Clinical Significance of Microcytosis in Patients with Primary Myelofibrosis

    PubMed Central

    Strati, Paolo; Pemmaraju, Naveen; Estrov, Zeev; Cardenas-Turanzas, Marylou; Pierce, Sherry; Newberry, Kate J.; Daver, Naval; Cortes, Jorge; Kantarjian, Hagop; Verstovsek, Srdan

    2014-01-01

    Microcytosis is a relatively frequent finding in primary myelofibrosis (PMF); however its prognostic significance is unknown. We identified factors associated with microcytosis in PMF and measured its impact on outcomes. Among 725 patients with PMF, 140 (19%) showed microcytosis. In multivariate analysis, factors associated with microcytosis were absence of prior therapy, low iron, low transferrin saturation (satTF), and splenomegaly. Among 375 untreated patients, low satTF and splenomegaly were associated with microcytosis. Overall, microcytosis was associated with a higher risk of transformation to leukemia (p=0.03), but not shorter leukemia-free survival. Microcytosis in PMF may be related to dysregulation of iron homeostasis. PMID:25217891

  4. Clinical significance of lymphadenectomy in patients with gastric cancer.

    PubMed

    Tóth, Dezső; Plósz, János; Török, Miklós

    2016-02-15

    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

  5. Expression and clinical significance of Sirt1 in colorectal cancer

    PubMed Central

    YU, DENG-FENG; JIANG, SU-JUAN; PAN, ZHI-PENG; CHENG, WEI-DONG; ZHANG, WEN-JUN; YAO, XIAO-KUN; LI, YU-CHENG; LUN, YONG-ZHI

    2016-01-01

    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. PMID:26893713

  6. Clinical significance of HOTAIR expression in colon cancer

    PubMed Central

    Luo, Zhi-Fen; Zhao, Dan; Li, Xi-Qing; Cui, Yong-Xia; Ma, Ning; Lu, Chuang-Xin; Liu, Ming-Yue; Zhou, Yun

    2016-01-01

    AIM: To detect the expression of the long noncoding RNA HOTAIR in colon cancer and analyze its relationship with clinicopathological parameters of colon cancer. METHODS: Total RNA was extracted from 80 colon cancer tissues and matched tumor-adjacent normal colon tissues and reverse transcribed. Quantitative polymerase chain reaction was used to detect the expression of HOTAIR. The relationship between the expression of HOTAIR and clinicopathological parameters of colon cancer was analyzed. RESULTS: The expression of HOTAIR was significantly higher in colon cancer tissues than in matched tumor-adjacent normal colon tissues (P < 0.05). HOTAIR expression was significantly higher in cases with lymph node metastasis than in those without metastasis; in lowly differentiated and undifferentiated cases than in highly and moderately differentiated cases; and in stages III + IV cases than in stages I + II cases (P < 0.05). CONCLUSION: HOTAIR expression is upregulated in colon cancer, suggesting that HOTAIR plays an important role in the tumorigenesis, development and metastasis of colon cancer. HOTAIR may act as an oncogene and represents a new molecular target for the treatment of colon cancer. PMID:27298568

  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. PMID:2066589

  8. 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

  9. Occult breast tumor reservoir: biological properties and clinical significance.

    PubMed

    Santen, Richard J; Yue, Wei; Heitjan, Daniel F

    2013-08-01

    Small, occult, undiagnosed breast cancers are found at autopsy in up to 15.6 % of women dying from unrelated causes with an average of 7 % from eight separate studies. The mammographic detection threshold of breast tumors ranges from 0.88 to 1.66 cm in diameter based on the patient's age. Tumor growth rates, expressed as "effective doubling times," vary from 10 to >700 days. We previously reported two models, based on iterative analysis of these parameters, to describe the biologic behavior of undiagnosed, occult breast tumors. Our models facilitate interpretation of the Women's Health Initiative (WHI) and antiestrogen breast cancer prevention studies. A nude mouse xenograft model was used to validate our assumption that breast tumors grow in a log-linear fashion. We then used our previously reported occult tumor growth (OTG) and computer-simulated tumor growth models to analyze various clinical trial data. Parameters used in the OTG model included a 200-day effective doubling time, 7 % prevalence of occult tumors, and 1.16 cm detection threshold. These models had been validated by comparing predicted with observed incidence of breast cancer in eight different populations of women. Our model suggests that menopausal hormone therapy with estrogens plus a progestogen (E + P) in the WHI trial primarily promoted the growth of pre-existing, occult lesions and minimally initiated de novo tumors. We provide a potential explanation for the lack of an increase in breast cancer incidence in the subgroup of women in the WHI who had not received E + P prior to randomization. This result may have reflected a leftward skew in the distribution of occult tumor doublings and insufficient time for stimulated tumors to reach the detection threshold. Our model predicted that estrogen alone reduced the incidence of breast cancer as a result of apoptosis. Understanding of the biology of occult tumors suggests that breast cancer "prevention" with antiestrogens or aromatase

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

    PubMed

    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

  11. Cohesin gene mutations in tumorigenesis: from discovery to clinical significance

    PubMed Central

    Solomon, David A.; Kim, Jung-Sik; Waldman, Todd

    2014-01-01

    Cohesin is a multi-protein complex composed of four core subunits (SMC1A, SMC3, RAD21, and either STAG1 or STAG2) that is responsible for the cohesion of sister chromatids following DNA replication until its cleavage during mitosis thereby enabling faithful segregation of sister chromatids into two daughter cells. Recent cancer genomics analyses have discovered a high frequency of somatic mutations in the genes encoding the core cohesin subunits as well as cohesin regulatory factors (e.g. NIPBL, PDS5B, ESPL1) in a select subset of human tumors including glioblastoma, Ewing sarcoma, urothelial carcinoma, acute myeloid leukemia, and acute megakaryoblastic leukemia. Herein we review these studies including discussion of the functional significance of cohesin inactivation in tumorigenesis and potential therapeutic mechanisms to selectively target cancers harboring cohesin mutations. [BMB Reports 2014; 47(6): 299-310] PMID:24856830

  12. Clinical and biological significance of precursor lesions of intrahepatic cholangiocarcinoma.

    PubMed

    Ettel, Mark; Eze, Ogechukwu; Xu, Ruliang

    2015-11-01

    Cholangiocarcinoma (CC) is primarily a malignant tumor of older adults most prevalent in Southeast Asia, where liver fluke infestation is high. However the etiology in western countries is unknown. Although the incidence of extrahepatic cholangiocarcinoma has remained constant, incidence of intrahepatic CC (ICC) which differs in morphology, pathogenesis, risk factors, treatment and prognosis is increasing. While this increase is associated with hepatitis C virus infection, chronic nonalcoholic liver disease, obesity, and smoking, the pathogenesis of ICC and molecular alterations underlying the carcinogenesis are not completely elucidated. Benign biliary lesions such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, von Meyenburg complex or bile duct hamartoma, and bile duct adenoma have been associated with ICC. For each of these entities, evidence suggests or supports a role as premalignant lesions. This article summarized the important biological significance of the precursor lesions of ICC and the molecular mechanisms that may be involved in intrahepatic cholangiocarcinogenesis. PMID:26557948

  13. Clinical and biological significance of precursor lesions of intrahepatic cholangiocarcinoma

    PubMed Central

    Ettel, Mark; Eze, Ogechukwu; Xu, Ruliang

    2015-01-01

    Cholangiocarcinoma (CC) is primarily a malignant tumor of older adults most prevalent in Southeast Asia, where liver fluke infestation is high. However the etiology in western countries is unknown. Although the incidence of extrahepatic cholangiocarcinoma has remained constant, incidence of intrahepatic CC (ICC) which differs in morphology, pathogenesis, risk factors, treatment and prognosis is increasing. While this increase is associated with hepatitis C virus infection, chronic nonalcoholic liver disease, obesity, and smoking, the pathogenesis of ICC and molecular alterations underlying the carcinogenesis are not completely elucidated. Benign biliary lesions such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, von Meyenburg complex or bile duct hamartoma, and bile duct adenoma have been associated with ICC. For each of these entities, evidence suggests or supports a role as premalignant lesions. This article summarized the important biological significance of the precursor lesions of ICC and the molecular mechanisms that may be involved in intrahepatic cholangiocarcinogenesis. PMID:26557948

  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. X-82 to Treat Age-related Macular Degeneration

    ClinicalTrials.gov

    2016-08-16

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

  16. Epidemiology and clinical significance of cervical erosion in women attending a family planning clinic.

    PubMed

    Goldacre, M J; Loudon, N; Watt, B; Grant, G; Loudon, J D; McPherson, K; Vessey, M P

    1978-03-25

    Women attending a family planning clinic were studied to determine the relation between cervical erosion and clinical and social characteristics. The appearance of the cervix was recorded without knowledge of the women's symptoms. The prevalence of erosion increased with parity but, when the effects of other factors were controlled, decreased in women aged 35 and over. Erosion was significantly more common in women taking the "pill" and less common in women using barrier methods of contraception than in others. There was considerable variation between doctors in the reporting of erosion. No association was found between erosion and postcoital bleeding, dyspareunia, backache, or dysuria. There was a significant but modest association between erosion and vaginal discharge and a suggestion that erosion may sometimes be associated with nocturia and frequency of micturition. Vaginal flora was similar in women with and without erosion. Cervical erosion should not be regarded as pathological in asymptomatic women, nor should it be assumed necessarily to be the cause of symptoms in women with genitourinary complaints. PMID:630328

  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 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. PMID:27084249

  19. 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

  20. Clinical significance of midkine expression in sporadic desmoid tumors

    PubMed Central

    KIM, HEE SUNG; KIM, JIN; NAM, KYUNG HAN; KIM, WOO HO

    2016-01-01

    The aim of the present study was to identify the prognostic factors for the propensity for recurrence in sporadic desmoid tumors. The catenin (cadherin-associated protein) β1 (CTNNB1) genotypes and expression of Wnt pathway proteins and midkine (also termed neurite growth-promoting factor 2) were investigated in 159 patients with sporadic desmoid tumors. Formalin-fixed paraffin-embedded tissues of the surgically resected desmoid tumors were examined by direct sequencing of CTNNB1 exon 3, and immunostained for the expression of β-catenin, T-cell factor 4 (TCF-4), phosphorylated protein kinase B (pAkt), midkine and menin using a tissue microarray method. Among the samples, 70% (111/159) exhibited point mutations of the CTNNB1 gene, including T41A (56%), S45F (8%), S45P (2%), S45N (2%) and T42A (1%). In addition, 100, 57, 24, 15 and 92% of the tumors expressed β-catenin, TCF-4, midkine, pAkt and menin, respectively. Positive midkine expression was significantly associated with the recurrence of tumors (P=0.001). The multivariate analysis of recurrence demonstrated that an extra-abdominal tumor site [hazard ratio (HR), 2.625; P=0.001] and midkine expression (HR, 2.077; P<0.009) were independent prognostic factors of tumor recurrence. In conclusion, the present results suggest that the tumor site and midkine expression may be predictive markers for the recurrence of sporadic desmoid tumors. PMID:26998061

  1. N-Cadherin in Neuroblastoma Disease: Expression and Clinical Significance

    PubMed Central

    Derycke, Lara; De Craemer, Annemie; De Brouwer, Sara; De Preter, Katleen; Van Roy, Nadine; Vandesompele, Jo; Speleman, Frank; Philippé, Jan; Benoit, Yves; Beiske, Klaus; Bracke, Marc; Laureys, Geneviève

    2012-01-01

    One of the first and most important steps in the metastatic cascade is the loss of cell-cell and cell-matrix interactions. N-cadherin, a crucial mediator of homotypic and heterotypic cell-cell interactions, might play a central role in the metastasis of neuroblastoma (NB), a solid tumor of neuroectodermal origin. Using Reverse Transcription Quantitative PCR (RT-qPCR), Western blot, immunocytochemistry and Tissue MicroArrays (TMA) we demonstrate the expression of N-cadherin in neuroblastoma tumors and cell lines. All neuroblastic tumors (n = 356) and cell lines (n = 10) expressed various levels of the adhesion protein. The N-cadherin mRNA expression was significantly lower in tumor samples from patients suffering metastatic disease. Treatment of NB cell lines with the N-cadherin blocking peptide ADH-1 (Exherin, Adherex Technologies Inc.), strongly inhibited tumor cell proliferation in vitro by inducing apoptosis. Our results suggest that N-cadherin signaling may play a role in neuroblastoma disease, marking involvement of metastasis and determining neuroblastoma cell viability. PMID:22355346

  2. Clinical significance of estrogen receptor beta in breast cancer.

    PubMed

    Saji, Shigehira; Hirose, Makiko; Toi, Masakazu

    2005-11-01

    Ever since the estrogen receptor (ER) beta was discovered in 1996, we have been trying to determine its value as a prognostic and/or predictive factor in breast cancer and its potential as a novel target for pharmacological intervention. Recent progress in cellular experiments has shown that ERbeta works as counter partner of ERalpha through inhibition of the transactivating function of ERalpha by heterodimerization, distinct regulation on several specific promoters by ERalpha or ERbeta, and ERbeta-specific regulated genes which are probably related to its anti-proliferative properties. Accumulated data from protein studies in breast cancer tissues indicate that positive expression of ERbeta appears to correlate with a favorable prognosis. Although the number of studies is small, a positive response to tamoxifen treatment is observed in both ERalpha- and ERbeta-positive populations. The significance of ERbeta2/cx, a splicing variant of ERbeta, remains controversial and needs to be analyzed in further studies. We postulate that a combined evaluation of ERbetacx with progesterone receptor may help the stratification of ERalpha-positive breast cancer. Epidemiological studies of hormone replacement therapy and isoflavone (genistein) consumption indicate the possible contribution of ERbeta-specific signaling in breast cancer prevention. A selective estrogen receptor modulator, which works as an antagonist of ERalpha and an agonist of ERbeta, may be a promising chemo-preventive treatment. PMID:16273360

  3. Therapeutic effect of intravitreal injections of ranibizumab for the treatment of macular choroidal neovascularization caused by pathological myopia

    PubMed Central

    JI, LEIBING; LV, WENJUAN; XIAO, YUN; XU, ZHENGHUA; ZHANG, XIAOLING; ZHANG, WEI

    2015-01-01

    The aim of the present study was to evaluate the clinical efficacy and safety of intravitreal ranibizumab injections for the treatment of macular choroidal neovascularization (CNV) caused by pathological myopia. Between one and four intravitreal injections of ranibizumab were administered to 61 eyes from 61 patients who were diagnosed with macular CNV caused by pathological myopia. Following injection, the best-corrected visual acuity (BCVA), central macular thickness (CMT) and fundus fluorescein angiography (FFA) findings were evaluated monthly for a period of 6 months. Among the 61 eyes, 10 eyes received one injection, 44 received two injections, six received three injections and one received four injections (average, 1.97 injections). The BCVA was 0.02±0.01 prior to treatment and 0.30±0.03 subsequent to treatment, and this difference was statistically significant (P<0.01). The CMT was reduced by an average of 45.1 µm. Regarding the FFA results, 56 eyes had no CNV fluorescence leakage and five eyes had CNV fluorescence leakage following treatment; however, the intensity of CNV fluorescence leakage in the five eyes following treatment was lower than that prior to treatment. As a treatment for pathological myopia-induced macular CNV, intravitreal injections of ranibizumab may improve eyesight as well as the macular retinal tissue structure; thus, this is a safe and effective treatment method. PMID:26622450

  4. Age-Related Macular Degeneration

    MedlinePlus

    ... this page please turn Javascript on. Age-related Macular Degeneration What is AMD? Click for more information Age-related macular degeneration, ... the macula allows you to see fine detail. AMD Blurs Central Vision AMD blurs the sharp central ...

  5. 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

  6. 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. PMID:24204114

  7. 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

  8. 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

  9. 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.

  10. Ascorbic acid repletion: A possible therapy for diabetic macular edema?

    PubMed

    May, James M

    2016-05-01

    Macular edema poses a significant risk for visual loss in persons with diabetic retinopathy. It occurs when plasma constituents and fluid leak out of damaged retinal microvasculature in the area of the macula, causing loss of central vision. Apoptotic loss of pericytes surrounding capillaries is perhaps the earliest feature of diabetic vascular damage in the macula, which is also associated with dysfunction of the endothelium and loss of the otherwise very tight endothelial permeability barrier. Increased oxidative stress is a key feature of damage to both cell types, mediated by excess superoxide from glucose-induced increases in mitochondrial metabolism, as well as by activation of the receptor for advanced glycation end products (RAGE). The latter in turn activates multiple pathways, some of which lead to increased oxidative stress, such as those involving NF-ĸB, NADPH oxidase, and endothelial nitric oxide synthase. Such cellular oxidative stress is associated with low cellular and plasma ascorbic acid levels in many subjects with diabetes in poor glycemic control. Whether repletion of low ascorbate in retinal endothelium and pericytes might help to prevent diabetic macular edema is unknown. However, cell culture studies show that the vitamin prevents high-glucose and RAGE-induced apoptosis in both cell types, that it preserves nitric oxide generated by endothelial cells, and that it tightens the leaky endothelial permeability barrier. Although these findings need to be confirmed in pre-clinical animal studies, it is worth considering clinical trials to determine whether adequate ascorbate repletion is possible and whether it might help to delay or even reverse early diabetic macular edema. PMID:26898503

  11. Biomarkers of treatment outcome in schizophrenia: Defining a benchmark for clinical significance.

    PubMed

    Levine, Stephen Z; Rabinowitz, Jonathan; Uher, Rudolf; Kapur, Shitij

    2015-10-01

    Emerging data from on imaging and genetic studies have generated interest in "clinically significant" biomarkers to predict response and prognosis. What constitutes "clinical significance" and how a biomarker would reach that threshold are unclear. To develop a benchmark we reviewed different approaches for defining "clinical significance" applied in schizophrenia research and identified that an improvement of 15 points on the PANSS Total is considered meaningful in clinical settings. Using this benchmark and we simulated thousands of schizophrenia trials, using characteristics derived from the NEWMEDS database with over 8000 patients with schizophrenia, to the kind of imaging, genetic, and other biomarkers that could attain clinical significance. We plotted the interaction between frequency-of-occurrence, the effect size of biomarkers and their relationship to the clinical significance threshold. Results show that categorical biomarkers are likely to attain clinical significance when they occur in 20-50% of the clinical population, and can predict at least a 8-10 point PANSS scale difference. Genetic markers are likely to have clinical significance when they occur in 20-50% of the population and can predict 7-9 points on the PANSS scale. A marker with a lower frequency or lesser effect size would find it hard to meet clinical significance thresholds for schizophrenia. The assumptions and limitations of this approach are discussed. Compared with standards in the rest of medicine, biomarkers that can attain this benchmark will be cost-effective and are likely to be adopted by clinical systems. PMID:26145487

  12. Clinical relevance vs. statistical significance: Using neck outcomes in patients with temporomandibular disorders as an example.

    PubMed

    Armijo-Olivo, Susan; Warren, Sharon; Fuentes, Jorge; Magee, David J

    2011-12-01

    Statistical significance has been used extensively to evaluate the results of research studies. Nevertheless, it offers only limited information to clinicians. The assessment of clinical relevance can facilitate the interpretation of the research results into clinical practice. The objective of this study was to explore different methods to evaluate the clinical relevance of the results using a cross-sectional study as an example comparing different neck outcomes between subjects with temporomandibular disorders and healthy controls. Subjects were compared for head and cervical posture, maximal cervical muscle strength, endurance of the cervical flexor and extensor muscles, and electromyographic activity of the cervical flexor muscles during the CranioCervical Flexion Test (CCFT). The evaluation of clinical relevance of the results was performed based on the effect size (ES), minimal important difference (MID), and clinical judgement. The results of this study show that it is possible to have statistical significance without having clinical relevance, to have both statistical significance and clinical relevance, to have clinical relevance without having statistical significance, or to have neither statistical significance nor clinical relevance. The evaluation of clinical relevance in clinical research is crucial to simplify the transfer of knowledge from research into practice. Clinical researchers should present the clinical relevance of their results. PMID:21658987

  13. 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

  14. Topical Latanoprost Does Not Cause Macular Thickening after Uncomplicated Cataract Surgery

    PubMed Central

    Moghimi, Sasan; Zandian, Mehdi; Latifi, Golshan; Amini, Heydar; Eslami, Yadollah; Zarei, Reza; Fakhraie, Ghasem; Nouri-Mahdavi, Kouros

    2012-01-01

    Purpose To explore changes in central macular thickness (CMT) after a two-month period of glaucoma therapy with topical latanoprost after uneventful phacoemulsification. Methods Forty-one eyes of 31 patients with primary open angle or pseudoexfoliative glaucoma who required glaucoma medications after cataract surgery were prospectively enrolled. All eyes had undergone uneventful phacoemulsification with intraocular lens implantation at least 4 months before initiation of latanoprost. After a complete ophthalmic examination, spectral-domain optical coherence tomography (SD-OCT) and fluorescein angiography (FA) were performed at baseline before starting latanoprost. All eyes received latanoprost for 2 months, and clinical examinations were repeated one and two months afterwards; OCT and FA were repeated after 2 months. Outcome measures were CMT and loss of more than 2 lines of best corrected visual acuity (BCVA). Results Mean patient age was 71.6±7.8 years. Intraocular pressure decreased from 21.5±3.4 mmHg to 14.4±2.6 mmHg (p<0.001) at 2 months. None of the eyes developed reduction of BCVA exceeding 2 lines, or angiographic cystoid macular edema (CME). Likewise no significant change was noted in CMT (249.9±29.8 vs 248.8±30.7µm), average macular thickness (274.5±15.0 vs 273.8±17.0µm), or macular volume (9.6±1.0 vs 9.6±1.1µm2) after treatment as compared to baseline (P>0.05 for all comparisons). Conclusion Topical use of latanoprost later than 4 months after uncomplicated cataract surgery does not seem to predispose to increased macular thickness or CME and may safely be used in this setting. PMID:23503128

  15. What Is Age-Related Macular Degeneration?

    MedlinePlus

    ... Degeneration Diagnosis: How is AMD diagnosed? Macular Degeneration Treatment: How is AMD Treated? Macular ... macular degeneration (AMD) is a deterioration or breakdown of the eye's macula. The macula is a small area in the ...

  16. Intraoperative Changes in Idiopathic Macular Holes by Spectral-Domain Optical Coherence Tomography

    PubMed Central

    Hayashi, Atsushi; Yagou, Takaaki; Nakamura, Tomoko; Fujita, Kazuya; Oka, Miyako; Fuchizawa, Chiharu

    2011-01-01

    Purpose To examine anatomical changes in idiopathic macular holes during surgery using handheld spectral-domain optical coherence tomography (SD-OCT). Methods Five eyes of 5 patients who underwent surgery for the repair of idiopathic macular holes were examined. The surgery included standard 25-gauge, 3-port pars plana vitrectomy, removal of the internal limiting membrane (ILM), fluid-air exchange, and 20% sulfur hexafluoride tamponade. Intraoperative SD-OCT images of the macular holes were obtained after ILM removal and under fluid-air exchange using a handheld SD-OCT. From SD-OCT images, the macular hole base diameter (MHBD) was measured and compared. Results All macular holes were successfully closed after the primary surgery. The mean MHBD under fluid-air exchange was significantly smaller than the mean MHBD after ILM removal and the preoperative mean MHBD. In 1 eye with a stage 3 macular hole, SD-OCT images revealed that the inner edges of the macular hole touched each other under fluid-air exchange. Conclusion Fluid-air exchange significantly reduced MHBD during surgery to repair macular holes. Fluid-air exchange may be an important step for macular hole closure as it reduces the base diameter of the macular hole. PMID:21677882

  17. Emerging Pharmacotherapies for Diabetic Macular Edema

    PubMed Central

    Javey, Golnaz; Schwartz, Stephen G.; Flynn, Harry W.

    2012-01-01

    Diabetic macular edema (DME) remains an important cause of visual loss in patients with diabetes mellitus. Although photocoagulation and intensive control of systemic metabolic factors have been reported to achieve improved outcomes in large randomized clinical trials (RCTs), some patients with DME continue to lose vision despite treatment. Pharmacotherapies for DME include locally and systemically administered agents. We review several agents that have been studied for the treatment of DME. PMID:22474425

  18. 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

  19. Macular Amyloidosis and Epstein-Barr Virus.

    PubMed

    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

  20. 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

  1. Intravitreal ketorolac for the treatment of chronic cystoid macular edema after cataract surgery

    PubMed Central

    Tsilimbaris, Miltiadis K; Tsika, Chrysanthi; Kymionis, George D

    2016-01-01

    Purpose To report two cases of chronic postoperative cystoid macular edema, resistant to topical therapy, treated with consecutive intravitreal injections of ketorolac tromethamine. Methods Four daily intravitreal injections of 500 μg/0.05 mL of ketorolac were given to each patient. Complete clinical examination and OCT were performed before every injection, 1, 2, 3 weeks, and 1, 3, and 6 months after the last injection. Fluorescein angiography was performed at baseline examination, 1, 3, and 6 months after the last injection. Results In both cases, the edema regressed and visual acuity increased. At 6 months after the last injection, the leakage was significantly reduced at the fluorescein angiography. Discussion Both cases responded favorably to the consecutive intravitreal administration of ketorolac tromethamine. The long-lasting remission of the macular edema in these chronic cases underlines the therapeutic potential of these agents when delivered intravitreally. PMID:26929630

  2. Macular Function in Macular Degenerations: Repeatability of Microperimetry as a Potential Outcome Measure for ABCA4-Associated Retinopathy Trials

    PubMed Central

    Swider, Malgorzata; Aleman, Tomas S.; Feuer, Willam J.; Schwartz, Sharon B.; Russell, Robert C.; Steinberg, Janet D.; Stone, Edwin M.; Jacobson, Samuel G.

    2012-01-01

    Purpose. To measure macular visual function in patients with unstable fixation, to define the photoreceptor source of this function, and to estimate its test-retest repeatability as a prerequisite to clinical trials. Methods. Patients (n = 38) with ABCA4-associated retinal degeneration (RD) or with retinitis pigmentosa (RP) were studied with retina-tracking microperimetry along the foveo-papillary profile between the fovea and the optic nerve head, and point-by-point test-retest repeatability was estimated. A subset with foveal fixation was also studied with dark-adapted projection perimetry using monochromatic blue and red stimuli along the horizontal meridian. Results. Macular function in ABCA4-RD patients transitioned from lower sensitivity at the parafovea to higher sensitivity in the perifovea. RP patients had the inverse pattern. Red-on-red microperimetric sensitivities successfully avoided ceiling effects and were highly correlated with absolute sensitivities. Point-by-point test-retest limits (95% confidence intervals) were ±4.2 dB; repeatability was not related to mean sensitivity, eccentricity from the fovea, age, fixation location, or instability. Repeatability was also not related to the local slope of sensitivity and was unchanged in the parapapillary retina. Conclusions. Microperimetry allows reliable testing of macular function in RD patients without foveal fixation in longitudinal studies evaluating natural disease progression or efficacy of therapeutic trials. A single estimate of test-retest repeatability can be used to determine significant changes in visual function at individual retinal loci within diseased regions that are homogeneous and those that are heterogeneous and also in transition zones at high risk for disease progression. PMID:22247458

  3. Age-related macular degeneration: choroidal ischaemia?

    PubMed Central

    Coleman, D Jackson; Silverman, Ronald H; Rondeau, Mark J; Lloyd, Harriet O; Khanifar, Aziz A; Chan, R V Paul

    2013-01-01

    Aim Our aim is to use ultrasound to non-invasively detect differences in choroidal microarchitecture possibly related to ischaemia among normal eyes and those with wet and dry age-related macular degeneration (AMD). Design Prospective case series of subjects with dry AMD, wet AMD and age-matched controls. Methods Digitised 20 MHz B-scan radiofrequency ultrasound data of the region of the macula were segmented to extract the signal from the retina and choroid. This signal was processed by a wavelet transform, and statistical modelling was applied to the wavelet coefficients to examine differences among dry, wet and non-AMD eyes. Receiver operating characteristic (ROC) analysis was used to evaluate a multivariate classifier. Results In the 69 eyes of 52 patients, 18 did not have AMD, 23 had dry AMD and 28 had wet AMD. Multivariate models showed statistically significant differences between groups. Multiclass ROC analysis of the best model showed an excellent volume-under-curve of 0.892±0.17. The classifier is consistent with ischaemia in dry AMD. Conclusions Wavelet augmented ultrasound is sensitive to the organisational elements of choroidal microarchitecture relating to scatter and fluid tissue boundaries such as seen in ischaemia and inflammation, allowing statistically significant differentiation of dry, wet and non-AMD eyes. This study further supports the association of ischaemia with dry AMD and provides a rationale for treating dry AMD with pharmacological agents to increase choroidal perfusion. ClinicalTrials.gov registration NCT00277784. PMID:23740965

  4. Calculating Clinically Significant Change: Applications of the Clinical Global Impressions (CGI) Scale to Evaluate Client Outcomes in Private Practice

    ERIC Educational Resources Information Center

    Kelly, Peter James

    2010-01-01

    The Clinical Global Impressions (CGI) scale is a therapist-rated measure of client outcome that has been widely used within the research literature. The current study aimed to develop reliable and clinically significant change indices for the CGI, and to demonstrate its application in private psychological practice. Following the guidelines…

  5. 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.…

  6. 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…

  7. 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

  8. The Association Between Subretinal Drusenoid Deposits in Older Adults in Normal Macular Health and Incident Age-Related Macular Degeneration

    PubMed Central

    Huisingh, Carrie; McGwin, Gerald; Neely, David; Zarubina, Anna; Clark, Mark; Zhang, Yuhua; Curcio, Christine A.; Owsley, Cynthia

    2016-01-01

    Purpose Subretinal drusenoid deposits (SDD) have been associated with the progression to late age-related macular degeneration (AMD). To determine whether SDD in eyes in normal macular health increases risk for early AMD, this study examined the association between presence of SDD at baseline in a cohort of older adults in normal macular health and incident AMD 3 years later. Methods Subjects enrolled in the Alabama Study on Early Age-Related Macular Degeneration (ALSTAR) were assessed for the presence of SDD using color fundus photos, infrared reflectance and fundus autofluorescence images, and spectral-domain optical coherence tomography volumes. The study sample included 799 eyes from 455 participants in normal macular health per grading of color fundus photographs using the 9-step Age-Related Eye Disease Study (AREDS) classification system. Age-related macular degeneration was defined as eyes having an AREDS grade ≥2 at the 3-year follow-up. Results Twenty-five percent of participants had SDD in one or both eyes at baseline. At follow-up visit, 11.9% of eyes in the sample developed AMD. Compared to eyes without SDD, those with SDD were 2.24 (95% confidence interval [CI] 1.36–3.70) times more likely to have AMD at follow-up. After adjusting for age, C-reactive protein quartile, and family history of AMD, the association persisted. Conclusions Results suggest that SDD in older eyes with normal macular health as defined by the AREDS scale is a risk factor for the development of early AMD. Older adults in seemingly normal macular health yet having SDD may warrant closer clinical monitoring for the possible onset of early AMD. PMID:26906160

  9. Expression and clinical significance of Beclin-1 in gastric cancer tissues of various clinical stages

    PubMed Central

    FEI, BINGYUAN; JI, FUJIAN; CHEN, XUEBO; LIU, ZHUO; LI, SHUO; MO, ZHANHAO; FANG, XUEDONG

    2016-01-01

    Autophagy is a common phenomenon in cancer metabolism. However the mechanism and guiding significance of autophagy in the development of gastric cancer has remained to be elucidated. In the present study, 75 gastric cancer tissue specimens were collected at The China Japan Union Hospital of Jilin University (Changchun, China). Of these samples, 16 cases were stage 1, 40 stage 2 and 19 stage 3. Polymerase chain reaction and western blotting were used to detect the messenger RNA and protein expression of Beclin-1, a significant protein associated with cellular autophagy. It was found that expression of Beclin-1 in cancer tissues from stages 1 and 2 was higher, while in stage 3 cases levels were significantly lower than that of adjacent normal tissues. In addition, the infiltration of inflammatory cytokines was also increased in stage 1 and 2 cases. In vitro studies revealed that following stimulation with interferon-γ (IFN-γ), autophagy-associated proteins Beclin-1 and microtubule-associated protein light chain 3 were activated. Furthermore, activation of autophagy inhibited xenograft growth in nude mice. The results of these in vivo and in vitro experiments indicated that in gastric cancer tissues, autophagy was downregulated following the development of cancer tissue and that inflammation may be a significant factor in this process. IFN-γ may be involved in the mediation of this process and thus present a novel target for the treatment of gastric cancer. PMID:26998161

  10. Prediction of spontaneous closure of traumatic macular hole with spectral domain optical coherence tomography

    PubMed Central

    Chen, Haoyu; Chen, Weiqi; Zheng, Kangken; Peng, Kun; Xia, Honghe; Zhu, Lei

    2015-01-01

    It has been known that some traumatic macular holes can close spontaneously. However, knowledge about the types of macular hole that can close spontaneously is limited. In this retrospective study, we investigated patients with traumatic macular hole who were followed-up for at least 6 months without any surgical intervention. Clinical data and spectral domain optical coherence tomography (SD-OCT) images were compared between groups with and without macular hole closure. Overall, 27 eyes were included. Spontaneous closure of macular hole was observed in 10 (37.0%) eyes. The holes with spontaneous closure had smaller minimum diameter (244.9 ± 114.4 vs. 523.9 ± 320.0 μm, p = 0.007) and less intraretinal cysts (10% vs. 76.5%, p = 0.001) compared to the holes that did not close spontaneously. The area under the curve of receiver operative characteristic was 0.812 and 0.832 for minimum diameter of macular hole and presence of intraretinal cysts respectively. Multivariate logistic regression showed that the presence of intraretinal cysts was an independent predictive factor for closure of macular holes. The group with spontaneous macular hole closure had a high chance of visual improvement. Our study suggests that the absence of intraretinal cysts on SD-OCT can predict spontaneous closure of traumatic macular hole. PMID:26196460

  11. Macular degeneration - age-related

    MedlinePlus

    Age-related macular degeneration (ARMD); AMD ... distorted and wavy. There may be a small dark spot in the center of your vision that ... leafy vegetables, may also decrease your risk of age-related macular degeneration. If you have wet AMD, ...

  12. Three-Month Outcome of Ziv-Aflibercept for Diabetic Macular Edema

    PubMed Central

    Marashi, Ameen

    2016-01-01

    Purpose Is to show the 3-month efficacy and safety of treatment diabetic macular edema treated with intravitreal ziv-aflibercept as studies have shown that Ziv-aflibercept does not cause retinal pigment epithelial toxicity and to study it cost effectiveness. Methods Ten eyes in eight patients diagnosed with central diabetic macular edema were enrolled for three consecutive intravitreal injection of ziv-aflibercept 1.25 mg every 4 weeks, a complete exam including BCVA and CRT at baseline and 12 weeks with evaluation of ocular and systemic complications. Results Improvement of best corrected visual acuity was clinically significant from baseline LogMAR 0.77 and 0.35 at 12 weeks and statistically significant (P<0.05) along with reduction of central retinal thickness from 562,4 μm and 317.7 μm at 12 weeks follow up (P<0.05) with no signs of ocular nor systemic complications. Conclusion Ziv aflibercept is a safe and effective in diabetic macular edema treatment for 12 weeks follow up with cost effectiveness especially in countries where aflibercept is not available. PMID:27347566

  13. Evidence of clinically significant change: the therapeutic alliance and the possibilities of outcomes-informed care.

    PubMed

    Manning, Walter H

    2010-11-01

    This article addresses the issue of clinically significant (or meaningful) change resulting from treatment for stuttering. Research in both medical and behavioral fields indicates that clients often have their own unique perspective of meaningful clinical change and that this perspective is often different from that of the professional administering the treatment. Among the variables that the client brings to the treatment session are their progression through stages of therapeutic change and the ways in which they believe they are capable of coping with their problem. Research has shown that how an individual interprets the meaning his or her therapeutic experience is central to clinically significant change. Procedures for obtaining feedback from clients concerning clinically significant change and the quality of the therapeutic alliance are described. PMID:21080293

  14. 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

  15. 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

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

    PubMed

    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

  17. 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

  18. Gut-directed hypnotherapy significantly augments clinical remission in quiescent ulcerative colitis

    PubMed Central

    Keefer, Laurie; Taft, Tiffany H; Kiebles, Jennifer L; Martinovich, Zoran; Barrett, Terrence A; Palsson, Olafur S

    2013-01-01

    Summary Background Psychotherapy is not routinely recommended for in ulcerative colitis (UC). Gut-directed hypnotherapy (HYP) has been linked to improved function in the gastrointestinal tract and may operate through immune-mediated pathways in chronic diseases. Aims To determine the feasibility and acceptability of hypnotherapy and estimate the impact of hypnotherapy on clinical remission status over a 1 year period in patients with an historical flare rate of 1.3 times per year. Methods 54 patients were randomized at a single site to 7 sessions of gut-directed hypnotherapy (N = 26) or attention control (CON; N = 29) and followed for 1 year. The primary outcome was the proportion of participants in each condition that had remained clinically asymptomatic (clinical remission) through 52 weeks post-treatment. Results One-way ANOVA comparing hypnotherapy and control subjects on number of days to clinical relapse favored the hypnotherapy condition [F = 4.8 (1, 48), p = .03] by 78 days. Chi square analysis comparing the groups on proportion maintaining remission at 1 year was also significant [X2(1) = 3.9, p = .04], with 68% of hypnotherapy and 40% of control patients maintaining remission for 1 year. There were no significant differences between groups over time in quality of life, medication adherence, perceived stress or psychological factors. Conclusions This is the first prospective study that has demonstrated a significant effect of a psychological intervention on prolonging clinical remission in patients with quiescent UC. Clinical Trial # NCT00798642 PMID:23957526

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

    PubMed Central

    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. Adolescents with eating disorders were expected to have higher levels of depression, anxiety, and trauma-related symptoms. Trauma-related symptoms were also examined in relation to BDD, in the absence of specific hypotheses. Method Participants completed the Body Dysmorphic Disorder Questionnaire (BDDQ) and reliable and valid self-report measures of suicidality, depression, anxiety, post-traumatic stress disorder (PTSD), dissociation, and sexual preoccupation/distress. Prevalence of BDD, eating disorders, and other clinically significant body image concerns was determined, and clinical correlates were examined. Results 6.7% (n = 14) of participants met DSM-IV criteria for definite (n = 10) or probable (n = 4) DSM-IV BDD, 3.8% (n = 8) met criteria for an eating disorder, and 22.1% (n = 46) had clinically significant shape/weight concerns (SWC) that did not clearly meet criteria for BDD or an eating disorder. Both the BDD and SWC groups scored significantly higher than the group with no significant body image concerns (no BDD/ED/SWC group) on measures of anxiety and suicidality. The BDD, SWC, and ED groups all had significantly higher levels of depression than the no BDD/ED/SWC group. Only the SWC group scored significantly higher than the no BDD/ED/SWC group on measures of PTSD, dissociation, and sexual preoccupation/distress. Conclusions A high proportion of participants had clinically significant body image concerns or a body image disorder. These concerns/disorders were associated with higher levels of depression, anxiety, and suicidality. In addition, the group concerned with body shape or weight had significantly greater

  20. Inpatient Treatment for Adolescents with Anorexia Nervosa: Clinical Significance and Predictors of Treatment Outcome.

    PubMed

    Schlegl, Sandra; Diedrich, Alice; Neumayr, Christina; Fumi, Markus; Naab, Silke; Voderholzer, Ulrich

    2016-05-01

    This study evaluated the clinical significance as well as predictors of outcome for adolescents with severe anorexia nervosa (AN) treated in an inpatient setting. Body mass index (BMI), eating disorder (ED) symptoms [Eating Disorder Inventory-2 (EDI-2)], general psychopathology and depression were assessed in 238 patients at admission and discharge. BMI increased from 14.8 + 1.2 to 17.3 + 1.4 kg/m(2). Almost a fourth (23.6%) of the patients showed reliable changes, and 44.7% showed clinically significant changes (EDI-2). BMI change did not significantly differ between those with reliable or clinically significant change or no reliable change in EDI-2. Length of stay, depression and body dissatisfaction were negative predictors of a clinically significant change. Inpatient treatment is effective in about two thirds of adolescents with AN and should be considered when outpatient treatment fails. About one third of patients showed significant weight gain, but did not improve regarding overall ED symptomatology. Future studies should focus on treatment strategies for non-responders. PMID:26603278

  1. Macular changes resulting from papilloedema.

    PubMed

    Morris, A T; Sanders, M D

    1980-03-01

    Six cases are presented with macular changes in association with papilloedema; 4 suffered permanent visual loss. The present paper emphasises this previously infrequent finding and discusses the haemodynamic and mechanical factors responsible. The macular changes consisted of haemorrhages situated in front, within, or behind the retina, and occasionally the results of neovascular membrane formation produced secondary visual loss. Changes in the pigment epithelium were seen in 3 cases associated with choroidal folds. Macular stars rarely produce visual loss. Recognition of these changes is important in the assessment of the visual loss in papilloedema. PMID:7387954

  2. [Clinical significance of prostate specific antigen and gamma-seminoprotein ratio for diagnosing prostate cancer].

    PubMed

    Akino, H; Suzuki, Y; Okada, K

    1998-08-01

    It has been reported that prostate specific antigen and gamma-seminoprotein ratio (PSA/gamma-Sm ratio) is an useful means for distinguishing benign prostatic hyperplasia and prostate cancer if serum PSA is measured by Eiken-PSA method. We studied the clinical significance of PSA/gamma-Sm ratio when using Markit-M-PSA method. PSA/gamma-Sm ratio had no superiority over PSA alone for detecting prostate cancer. The present results suggest that the clinical significance of PSA/gamma-Sm ratio can be varied by various PSA-assay kits. PMID:9750496

  3. 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. PMID:23463942

  4. 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 Central

    Beatty, Stephen; Perez-Salvador Garcia, Eduardo; Reynders, Stefaan; 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. PMID:24868458

  5. Effect of selective laser trabeculoplasty on macular thickness

    PubMed Central

    Koc, Mustafa; Durukan, Irfan; Koban, Yaran; Ceran, Basak Bastanci; Ayar, Orhan; Ekinci, Metin; Yilmazbas, Pelin

    2015-01-01

    Background To investigate the effects of selective laser trabeculoplasty (SLT) on macular thickness change. Methods Forty eyes of 40 consecutive patients with uncontrolled primary open-angle glaucoma with medical treatment were included in this prospective study. SLT was performed to the inferior 180°, and macular thickness was measured. Data were collected before SLT, and 1 week and 1 month after SLT. Macular thickness evaluation was performed in five quadrants, the central 1 mm quadrant (fovea = F), the nasal 3 mm quadrant surrounding F (NQ), temporal quadrant, superior quadrant (SQ), and inferior quadrant (IQ). The preoperative and postoperative thicknesses were compared. Results There was an increase in macular thickness in the NQ, IQ, and SQ on the first week after SLT compared to preoperative measurements. On the other hand, there was no significant increase in the F and temporal quadrant. On the first month after SLT, thickness in the NQ, IQ, and SQ was back to preoperative measurements, and there was no significant change between the preoperative measurements in any quadrant. Conclusion There was no significant increase in macular thickness shortly after SLT in our study. PMID:26719665

  6. 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...

  7. Bilateral choroidal excavation in best vitelliform macular dystrophy.

    PubMed

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

    2014-01-01

    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.]. PMID:24512759

  8. [Optical coherence tomography and fundus autofluorescence in Best macular dystrophy].

    PubMed

    Chebil, A; Charfi, H; Largueche, L; El Matri, L

    2016-06-01

    Best vitelliform macular dystrophy is the second most frequent hereditary maculopathy, with bilateral involvement and juvenile onset. It is clinically characterized by bilateral deposits of lipofuscin-like autofluorescent material in the subretinal space, with a typical phenotypic manifestation taking the form of a vitelliform macular lesion evolving gradually into more advanced stages. The purpose of our study was to describe fundus autofluorescence patterns and OCT findings in three patients (6 eyes) with several stages of Best vitelliform macular dystrophy. Optical coherence tomography (OCT) has become the first imaging technique to order when confronted with a hereditary maculopathy suggesting Best disease. Fundus autofluorescence combined with OCT allow for better diagnosis and management, which are necessary for any genetic analysis. PMID:27206620

  9. 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

  10. 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…

  11. 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…

  12. Clinical Significance: A Statistical Approach to Defining Meaningful Change in Psychotherapy Research.

    ERIC Educational Resources Information Center

    Jacobson, Neil S.; Truax, Paula

    1991-01-01

    Describes ways of operationalizing clinically significant change, defined as extent to which therapy moves someone outside range of dysfunctional population or within range of functional population. Uses examples to show how clients can be categorized on basis of this definition. Proposes reliable change index (RC) to determine whether magnitude…

  13. 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…

  14. Expression and clinical significance of cytochrome c oxidase subunit IV in colorectal cancer patients

    PubMed Central

    Zhang, Kun; Chen, Yibing; Huang, Xiaojun; Qu, Ping; Pan, Qiuzhong; Lü, Lin; Jiang, Shanshan; Su, Haichuan

    2016-01-01

    Introduction Previous studies have demonstrated that the expression of cytochrome c oxidase (COX) subunits encoded by mitochondrial DNA is elevated in colorectal cancer (CRC). However, the expression of nuclear DNA-encoded COX IV and its clinical significance have not yet been investigated in CRC. Material and methods We examined COX IV expression in paired CRC samples (cancer and pericancerous tissues) by quantitative real-time polymerase chain reaction (qPCR), Western blot and immunohistochemical staining and analyzed its clinical significance. Results qPCR and Western blot analyses showed that COX IV expression was significantly elevated at both the mRNA (p = 0.05) and protein levels in CRC tissue samples when compared with those in paired pericancerous tissues. Immunohistochemistry also revealed that COX IV expression was significantly increased in CRC tissues (p < 0.001). Association analyses showed that there was no significant association between COX IV expression and clinical parameters of CRC patients except for gender (p = 0.017). Moreover, we did not find any association between COX IV expression and overall survival or recurrence-free survival of CRC patients. Further analysis showed no significant relationship between the expression of COX IV and proliferating cell nuclear antigen (PCNA), a marker of cell proliferation. Conclusions Our findings suggest that elevated COX IV expression may play an important role in colorectal carcinogenesis, but not in progression, which warrants further investigation in future studies. PMID:26925120

  15. 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. PMID:26283461

  16. Fellow Eye Macular Edema Improvement after Intravitreal Bevacizumab for Radiation Retinopathy

    PubMed Central

    Brito, Isis A. S.; Zacharias, Leandro C.; Pimentel, Sérgio Luis G.

    2015-01-01

    Radiation retinopathy (RR) is a progressive, chronic condition directly related to the amount of radiation administered to the retina. We report a 37-year-old patient with medulloblastoma that was treated with external beam radiation and presented to us with bilateral cystoid macular edema. He was treated with monthly bevacizumab injections only in his worst seeing eye. There was a significant improvement in his fellow eye, with marked retinal thickness reduction. Therefore, we present clinical evidence of systemic absorption and fellow eye activity of the drug (bevacizumab). One must be aware of distant side effects after intravitreal injections. PMID:26635985

  17. Pharmacogenetics and age-related macular degeneration.

    PubMed

    Schwartz, Stephen G; Brantley, Milam A

    2011-01-01

    Pharmacogenetics seeks to explain interpatient variability in response to medications by investigating genotype-phenotype correlations. There is a small but growing body of data regarding the pharmacogenetics of both nonexudative and exudative age-related macular degeneration. Most reported data concern polymorphisms in the complement factor H and age-related maculopathy susceptibility 2 genes. At this time, the data are not consistent and no definite conclusions may be drawn. As clinical trials data continue to accumulate, these relationships may become more apparent. PMID:22046503

  18. Diabetic Macular Edema

    PubMed Central

    Gundogan, Fatih C.; Yolcu, Umit; Akay, Fahrettin; Ilhan, Abdullah; Ozge, Gokhan; Uzun, Salih

    2016-01-01

    Diabetic macular edema (DME), one the most prevalent causes of visual loss in industrialized countries, may be diagnosed at any stage of diabetic retinopathy. The diagnosis, treatment, and follow up of DME have become straightforward with recent developments in fundus imaging, such as optical coherence tomography. Laser photocoagulation, intravitreal injections, and pars plana vitrectomy surgery are the current treatment modalities; however, the positive effects of currently available intravitreally injected agents are temporary. At this point, further treatment choices are needed for a permanent effect. Sources of data selection: The articles published between 1985-2015 years on major databases were searched and most appropriate 40 papers were used to write this review article. PMID:27182271

  19. Clinical significance of immunohistochemically detected extracellular matrix proteins and their spatial distribution in primary cancer.

    PubMed

    Čunderlíková, B

    2016-09-01

    Our understanding of cancer has evolved mainly from results of studies utilizing experimental models. Simplification inherent to in vitro cell culture models enabled potential ways of cell behaviour in response to various external stimuli to be described, but it has led also to disappointments in clinical trials, presumably due to the lack of crucial tissue components, including extracellular matrix (ECM). ECM and its role in healthy and diseased tissues are being explored extensively and significance of ECM for cell behaviour has been evidenced experimentally. Part of the information gathered in such research that is relevant for natural conditions of a human body can be identified by carefully designed analyses of human tissue samples. This review summarizes published information on clinical significance of ECM in cancer and examines whether effects of ECM on cell behaviour evidenced in vitro, could be supported by clinically based data acquired from analysis of tissue samples. Based on current approaches of clinical immunohistochemical analyses, impact of ECM components on tumour cell behaviour is vague. Except of traditionally considered limitations, other reasons may include lack of stratification of analyzed cases based on clinicopathologic parameters, inclusion of patients treated postoperatively by different treatments or neglecting complexity of interactions among tumour constituents. Nevertheless, reliable immunohistochemical studies represent a source of crucial information for design of tumour models comprising ECM corresponding to real clinical situation. Knowledge gathered from such immunohistochemical studies combined with achievements in tissue engineering hold promise for reversal of the unfavourable trends in the current translational oncologic research. PMID:27443915

  20. Comparison and interchangeability of macular thickness measured with Cirrus OCT and Stratus OCT in myopic eyes

    PubMed Central

    Wang, Geng; Qiu, Kun-Liang; Lu, Xue-Hui; Zhang, Ming-Zhi

    2015-01-01

    AIM To investigate the difference of macular thickness measurements between stratus optical coherence tomography (OCT) and Cirrus OCT (Carl Zeiss Meditec, Dublin, CA, USA) in the same myopic patient and to develop a conversion equation to interchange macular thickness obtained with these two OCT devices. METHODS Eighty-nine healthy Chinese adults with spherical equivalent (SE) ranging from -1.13 D to -9.63 D were recruited. The macular thickness was measured by Cirrus OCT and Stratus OCT. The correlation between macular thickness and axial length and the agreement between two OCT measurements were evaluated. A formula was generated to interchange macular thickness obtained with two OCT devices. RESULTS Average macular thickness measured with Stratus OCT (r=-0.280, P=0.008) and Cirrus OCT (r=-0.224, P=0.034) were found to be negatively correlated with axial length. No statistically significant correlation was found between axial length and central subfield macular thickness (CMT) measured with Stratus OCT (r=0.191, P=0.073) and Cirrus OCT (r=0.169, P=0.113). The mean CMT measured with Cirrus OCT was 53.63±7.94 µm thicker than with Stratus OCT. The formula CMTCirrus OCT=78.328+0.874×CMTStratus OCT was generated to interchange macular thickness obtained with two OCT devices. CONCLUSION Macular thickness measured with Cirrus OCT were thicker than with Stratus OCT in myopic eyes. A formula can be used to interchange macular thickness measured with two OCT devices in myopic eyes. Studies with different OCT devices and larger samples are warranted to enable the comparison of macular values measured with different OCT devices. PMID:26682172

  1. Detection of Clinically Significant Retinopathy of Prematurity Using Wide-angle Digital Retinal Photography

    PubMed Central

    Chiang, Michael F.; Melia, Michele; Buffenn, Angela N.; Lambert, Scott R.; Recchia, Franco M.; Simpson, Jennifer L.; Yang, Michael B.

    2013-01-01

    Objective To evaluate the accuracy of detecting clinically significant retinopathy of prematurity (ROP) using wide-angle digital retinal photography. Methods Literature searches of PubMed and the Cochrane Library databases were conducted last on December 7, 2010, and yielded 414 unique citations. The authors assessed these 414 citations and marked 82 that potentially met the inclusion criteria. These 82 studies were reviewed in full text; 28 studies met inclusion criteria. The authors extracted from these studies information about study design, interventions, outcomes, and study quality. After data abstraction, 18 were excluded for study deficiencies or because they were superseded by a more recent publication. The methodologist reviewed the remaining 10 studies and assigned ratings of evidence quality; 7 studies were rated level I evidence and 3 studies were rated level III evidence. Results There is level I evidence from ≥5 studies demonstrating that digital retinal photography has high accuracy for detection of clinically significant ROP. Level III studies have reported high accuracy, without any detectable complications, from real-world operational programs intended to detect clinically significant ROP through remote site interpretation of wide-angle retinal photographs. Conclusions Wide-angle digital retinal photography has the potential to complement standard ROP care. It may provide advantages through objective documentation of clinical examination findings, improved recognition of disease progression by comparing previous photographs, and the creation of image libraries for education and research. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references. PMID:22541632

  2. [Further understanding on myocardial damage in the early stage post severe burn and its clinical significance].

    PubMed

    Huang, Y S

    2016-05-20

    A series of studies demonstrated that myocardial damage and cardiac dysfunction occurs immediately following severe burn, even before significant reduction in blood volume due to increased capillary permeability. Such myocardial damage and cardiac dysfunction leads to cardiac deficiency, and it is a precipitating factor for burn shock and ischemic/hypoxic injury. In recent years, many experimental and clinical studies elucidated the pathogenesis and confirmed the clinical importance of prevention and treatment of"shock heart"in the early stage post severe burn. PMID:27188482

  3. HyperModules: identifying clinically and phenotypically significant network modules with disease mutations for biomarker discovery

    PubMed Central

    Leung, Alvin; Bader, Gary D.; Reimand, Jüri

    2014-01-01

    Summary: Correlating disease mutations with clinical and phenotypic information such as drug response or patient survival is an important goal of personalized cancer genomics and a first step in biomarker discovery. HyperModules is a network search algorithm that finds frequently mutated gene modules with significant clinical or phenotypic signatures from biomolecular interaction networks. Availability and implementation: HyperModules is available in Cytoscape App Store and as a command line tool at www.baderlab.org/Sofware/HyperModules. Contact: Juri.Reimand@utoronto.ca or Gary.Bader@utoronto.ca Supplementary information: Supplementary data are available at Bioinformatics online PMID:24713437

  4. Clinical significance of Angiopoietin-1 in Behcet's disease patients with vascular involvement.

    PubMed

    Bassyouni, Iman H; Sharaf, Mohammed; Wali, Iman E; Mansour, Hossam M

    2016-06-01

    Behcet's disease (BD) is a chronic multisystem inflammatory disorder of unclear etiology. Vascular inflammation, endothelial dysfunction and angiogenesis may be in part responsible for the pathogenesis of BD. Angiopoietin-1 (Ang-1) is a recent angiogenic mediator. The aim of the present study was to assess Ang-1 in the plasma of BD patients as well as to analyze its association with clinical, and laboratory parameters of the disease. The present study included 47 BD patients and 30 age- and gender-matched healthy controls. Demographic, clinical, disease activity and severity were prospectively assessed. Plasma Ang-1 levels were measured using enzyme-linked immunosorbent assay. The plasma level of Ang-1 in BD patients was significantly lower than healthy controls (p = 0.005). Plasma Ang-1 level in patients with vascular affection was significantly lower than those without vascular affection (p = 0.045). Levels of Ang-1 showed a significant positive correlation with steroid dose. Patients who received cyclophosphamide or steroids showed a significant increase in plasma Ang-1 level. This was further confirmed by the results of the multivariate analysis. There was no significant association between plasma Ang-1 levels and other clinical manifestations or disease activity and severity. Plasma Ang-1 levels were diminished in our BD patients especially in patients with vascular involvement. Larger studies with further investigations of the precise role of Ang-1 in the pathogenesis of BD are needed and might lead to novel therapies for the clinical management of BD. PMID:25964071

  5. 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

  6. Clinical significance of RET mutation screening in a pedigree of multiple endocrine neoplasia type 2A.

    PubMed

    Ying, Rongbiao; Feng, Jun

    2016-08-01

    The clinical characteristics and RET proto-oncogene (RET‑PO) mutation status of a patient with multiple endocrine neoplasia type 2A pedigree (MEN2A) was analyzed with the aim of preliminarily exploring the molecular mechanisms and clinical significance of the disease. Clinical characteristics of a single MEN2A patient were analyzed. Genomic DNA was extracted from the peripheral blood of the proband and 10 family members. The 21 exons of RET‑PO were PCR amplified and the amplified products were sequenced. Of the family members, 5 exhibited a C634Y (TGC→TAC) missense mutation in exon 11 of RET‑PO, among which 2 family members were screened as mutation carriers, while the others did not exhibit clinical symptoms of the mutation. The screening and analysis of RET‑PO mutations for the MEN2A proband and the family members suggests potential clinical phenotypes and enables assessment of the risk of disease development, thus providing useful information for determining the surgical timing of preventive thyroid gland removal. PMID:27277749

  7. Clinical Significance of Histological Features of Thrombi in Patients with Myocardial Infarction

    PubMed Central

    Sebben, Juliana Canedo; Cambruzzi, Eduardo; Avena, Luisa Martins; Gazeta, Cristina do Amaral; Gottschall, Carlos Antonio Mascia; de Quadros, Alexandre Schaan

    2013-01-01

    Background Percutaneous Coronary Intervention (PCI) is the most common strategy for the treatment of Acute ST segment elevation Myocardial Infarction (STEMI), and thromboaspiration has been increasingly utilized for removal of occlusive thrombi. Objectives To analyze the influence of histopathological features of coronary thrombi in clinical outcomes of patients with STEMI, and the association of these variables with clinical, angiographic, and laboratory features and medications used in hospitalization. Methods Prospective cohort study. All patients were monitored during hospitalization and thirty days after the event. Aspirated thrombi were preserved in formalin and subsequently stained with hematoxylin-eosin and embedded in paraffin. Thrombi were classified as recent and old. The primary outcome was the occurrence of major cardiovascular events within thirty days. Results During the study period, 1,149 patients were evaluated with STEMI, and 331 patients underwent thrombi aspiration, leaving 199 patients available for analysis. It was identified recent thrombi in 116 patients (58%) and old thrombi in 83 patients (42%). Recent thrombi have greater infiltration of red blood cells than old thrombi (p = 0.02), but there were no statistically significant differences between other clinical, angiographic, laboratory, and histopathological features and medications in both group of patients. The rates of clinical outcomes were similar in both groups. Conclusions Recent thrombi were identified in 58% of patients with STEMI and it was observed an association with infiltration of red blood cells. There was no association between histopathological features of thrombi and clinical variables and cardiovascular outcomes. PMID:24162472

  8. Review of Ingested and Aspirated Foreign Bodies in Children and Their Clinical Significance for Radiologists.

    PubMed

    Pugmire, Brian S; Lim, Ruth; Avery, Laura L

    2015-01-01

    Ingested and aspirated foreign bodies are a common occurrence in children and are important causes of morbidity and mortality in the pediatric population. Imaging plays an important role in the diagnosis of ingested and aspirated foreign bodies in children and can be crucial to guiding the clinical management of these patients. Prompt identification and localization of ingested foreign bodies is essential to determining the appropriate treatment, as several types of commonly ingested foreign bodies require urgent removal and others can be managed conservatively. In particular, disk batteries impacted in the esophagus carry a high risk of esophageal injury or perforation; multiple ingested magnets can become attracted to each other across bowel walls and cause bowel perforation and fistula formation; and sharp objects commonly cause complications as they pass through the gastrointestinal tract. Accordingly, these ingested foreign bodies warrant aggressive clinical management and therefore radiologists must be familiar with their imaging appearances and clinical implications. Prompt recognition of secondary radiographic signs of foreign-body aspiration is also crucial, as clinical symptoms can sometimes be nonspecific and most aspirated foreign bodies are radiolucent. Overall, radiography is the most important modality in the evaluation of ingested or aspirated foreign bodies; however, fluoroscopy and computed tomography play an ancillary role in complicated cases. It is essential that every radiologist who interprets imaging examinations of children be aware of the imaging appearances of commonly ingested and aspirated foreign bodies and their clinical significance. PMID:26295734

  9. [Expression and clinical significance of Ki-67 in diffuse large B cell lymphoma].

    PubMed

    Zhou, Ying; Zhao, Yu; Bo, Jian; Li, Yan-Fen; Ma, Chao; Shi, Ya-Nan

    2013-10-01

    This study was aimed to evaluate the proliferation-associated antigen Ki-67 expression in diffuse large B cell lymphoma (DLBCL) and its clinical significance. The Ki-67 expression and its correlation with prognosis in 50 patients with DLBCL treated with rituximab plus CHOP (R-CHOP) between January 2008 and December 2010 were analyzed retrospectively. The results indicated that there was no significant relationship between Ki-67 expression and clinical features, including age, sex, staging, B symptoms, LDH level, IPI, extranodal site involvement, presence of bulky tumors (>10 cm in diameter), bone marrow involvement, GCG nor GCB type, or response to first line treatment. The median survival was 50 months and 15 months in low Ki-67 expression group (<85%) and in high Ki-67 expression group ( ≥ 85%) respectively. The overall survival (OS) and progress-free survival (PFS) in low Ki-67 expression group were obviously longer than that in high Ki-67 expression group (P = 0.001; P = 0.027). In univariate analysis, the clinical factors associated with OS included Ann Arbor staging and Ki-67 expression. The clinical factors associated with PFS included Ann Arbor staging. IPI and Ki-67 expression. In multivariate analysis. The Ki-67 expression level was an independent prognostic factor for OS (HR = 4.90; 95% CI, 1.456-16.511; P = 0.0103). It is concluded that Ki-67 expression level seems to be an effective marker for evaluation of DLBCL prognosis. PMID:24156426

  10. Macular Degeneration - Multiple Languages: MedlinePlus

    MedlinePlus

    ... Are Here: Home → Multiple Languages → All Health Topics → Macular Degeneration URL of this page: https://www.nlm.nih. ... V W XYZ List of All Topics All Macular Degeneration - Multiple Languages To use the sharing features on ...

  11. An unusual complication of blunt ocular trauma: A horseshoe-shaped macular tear with spontaneous closure

    PubMed Central

    Karaca, Umut; Durukan, Hakan A; Mumcuoglu, Tarkan; Erdurman, Cuneyt; Hurmeric, Volkan

    2014-01-01

    A case of horseshoe-shaped macular tear after blunt trauma with the course of the tear and the relevant findings obtained by spectral-domain optical coherence tomography (SD-OCT) is described. A 21-year-old man who had suffered blunt trauma 5 days previously visited our clinic complaining of vision loss in his left eye. Ophthalmic examination and SD-OCT images revealed a horseshoe-shaped macular tear. A month later at the second visit, the macular tear was found to have spontaneously closed. There have been many cases reported previously of the spontaneous closure of traumatic macular holes. A horseshoe-shaped macular tear is an atypical clinical presentation. However, the mechanism of spontaneous closure is hypothetically as same as that for a macular hole. High-resolution images and three-dimensional maps taken with SD-OCT can provide more details on macular diseases and are more useful than time-domain OCT images. PMID:24817754

  12. Quantifying clinically significant change: a brief review of methods and presentation of a hybrid approach.

    PubMed

    Mann, Barton J; Gosens, Taco; Lyman, Stephen

    2012-10-01

    Treatment outcome researchers in orthopaedics frequently report only tests of statistical significance between group means to evaluate the effectiveness of a given intervention. Although important in establishing that mean differences are not caused by chance, these methods do not reflect the extent to which an intervention produces improvements that are meaningful and represent a return to health. This is an issue that is often of great interest to patients and clinicians. Other methods use a percentage change in an outcome measure (eg, 25% reduction in pain score) to classify treatment responders but often do not indicate whether the treatment restored a patient to normal. Researchers have developed several indices that provide a metric for statistically defining the amount of change that patients consider to be important. In this article, we focus on the concept of "clinical significance" and the different methods that have been developed to define clinically significant change using statistics. We then present a hybrid method that can classify whether a patient has returned to normal function. We apply this method to real patient data to illustrate its use with different outcome instruments commonly used in orthopaedic sports medicine. We advocate that the addition of these methods to reports from clinical outcome studies can deepen our understanding of the impact of interventions on patients' lives. PMID:22962295

  13. Clinical Significance of Additional Ablation of Atrial Premature Beats after Catheter Ablation for Atrial Fibrillation

    PubMed Central

    Kim, In-Soo; Yang, Pil-Sung; Kim, Tae-Hoon; Park, Junbeum; Park, Jin-Kyu; Uhm, Jae Sun; Joung, Boyoung; Lee, Moon Hyoung

    2016-01-01

    Purpose The clinical significance of post-procedural atrial premature beats immediately after catheter ablation for atrial fibrillation (AF) has not been clearly determined. We hypothesized that the provocation of immediate recurrence of atrial premature beats (IRAPB) and additional ablation improves the clinical outcome of AF ablation. Materials and Methods We enrolled 200 patients with AF (76.5% males; 57.4±11.1 years old; 64.3% paroxysmal AF) who underwent catheter ablation. Post-procedure IRAPB was defined as frequent atrial premature beats (≥6/min) under isoproterenol infusion (5 µg/min), monitored for 10 min after internal cardioversion, and we ablated mappable IRAPBs. Post-procedural IRAPB provocations were conducted in 100 patients. We compared the patients who showed IRAPB with those who did not. We also compared the IRAPB provocation group with 100 age-, sex-, and AF-type-matched patients who completed ablation without provocation (No-Test group). Results 1) Among the post-procedural IRAPB provocation group, 33% showed IRAPB and required additional ablation with a longer procedure time (p=0.001) than those without IRAPB, without increasing the complication rate. 2) During 18.0±6.6 months of follow-up, the patients who showed IRAPB had a worse clinical recurrence rate than those who did not (27.3% vs. 9.0%; p=0.016), in spite of additional IRAPB ablation. 3) However, the clinical recurrence rate was significantly lower in the IRAPB provocation group (15.0%) than in the No-Test group (28.0%; p=0.025) without lengthening of the procedure time or raising complication rate. Conclusion The presence of post-procedural IRAPB was associated with a higher recurrence rate after AF ablation. However, IRAPB provocation and additional ablation might facilitate a better clinical outcome. A further prospective randomized study is warranted. PMID:26632385

  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. Clinicopathologic findings in Best vitelliform macular dystrophy

    PubMed Central

    Zhang, Qing; Small, Kent W.

    2012-01-01

    Purpose To correlate the clinical and histopathologic features of Best vitelliform macular dystrophy (BVMD). Methods Two eyes were obtained postmortem from a patient with BVMD. The patient’s clinical information was reviewed. Series sections of the globes were performed and sequentially stained with hematoxylin-eosin, periodic acid-Schiff or Masson trichrome. A section of the left macula was submitted for electron microscopic processing. Histopathologic findings were reconstructed in a scaled two-dimensional map and compared with fundus photography, fundus autofluorescence (FAF), fundus fluorescein angiography (FFA) and optical coherence tomography (OCT) images. Results The macular lesion of the right eye was identified as a well-demarcated region with pigment, elevated submacular yellow material and subretinal fluid. This corresponded histopathologically to a well-circumscribed area of RPE hyperplasia, accumulation of lipofuscin in the RPE, deposition of granular material in the photoreceptors, macrophages and drusen. The left eye displayed a 1 disc diameter chorioretinal scar with surrounding shallow fluid and submacular pigment. This corresponded to RPE changes and a fibrocellular proliferation in the choriocapillaris. Conclusion Histopathologic mapping revealed retinal edema, RPE abnormalities, drusen and a chorioretinal scar in BVMD that correlated with the fundus, FFA, FAF and OCT findings. PMID:21136072

  16. Twenty-five-gauge vitrectomy versus 23-gauge vitrectomy in the management of macular diseases: a comparative analysis through a Health Technology Assessment model.

    PubMed

    Grosso, Andrea; Charrier, Lorena; Lovato, Emanuela; Panico, Claudio; Mariotti, Cesare; Dapavo, Giancarlo; Chiuminatto, Roberto; Siliquini, Roberta; Gianino, Maria Michela

    2014-04-01

    Small-gauge vitreoretinal techniques have been shown to be safe and effective in the management of a wide spectrum of vitreoretinal diseases. However, the costs of the new technologies may represent a critical issue for national health systems. The aim of the study is to plan a Health Technology Assessment (HTA) by performing a comparative analysis between the 23- and 25-gauge techniques in the management of macular diseases (epiretinal membranes, macular holes, vitreo-macular traction syndrome). In this prospective study, 45-80-year-old patients undergoing vitrectomy surgery for macular disease were enrolled at the Torino Eye Hospital. In the HTA model we assessed the safety, clinical effectiveness, and cost and financial evaluation of 23-gauge compared with 25-gauge vitrectomies. Fifty patients entered the study; 14 patients underwent 23-gauge vitrectomy and 36 underwent 25-gauge vitrectomy. There was no statistically significant difference in post-operative visual acuity at 1 year between the two groups. No cases of retinal detachment or endophtalmitis were registered at 1-year follow-up. The 23-gauge technique was slightly more expensive than the 25-gauge: the total surgical costs were EUR1217.70 versus EUR1164.84 (p = 0.351). We provide a financial comparison between new vitreoretinal procedures recently introduced in the market and reimbursed by the Italian National Health System and we also stimulate a critical debate about the expensive technocratic model of medicine. PMID:24014147

  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. Cortical superficial siderosis: detection and clinical significance in cerebral amyloid angiopathy and related conditions.

    PubMed

    Charidimou, Andreas; Linn, Jennifer; Vernooij, Meike W; Opherk, Christian; Akoudad, Saloua; Baron, Jean-Claude; Greenberg, Steven M; Jäger, Hans Rolf; Werring, David J

    2015-08-01

    Cortical superficial siderosis describes a distinct pattern of blood-breakdown product deposition limited to cortical sulci over the convexities of the cerebral hemispheres, sparing the brainstem, cerebellum and spinal cord. Although cortical superficial siderosis has many possible causes, it is emerging as a key feature of cerebral amyloid angiopathy, a common and important age-related cerebral small vessel disorder leading to intracerebral haemorrhage and dementia. In cerebral amyloid angiopathy cohorts, cortical superficial siderosis is associated with characteristic clinical symptoms, including transient focal neurological episodes; preliminary data also suggest an association with a high risk of future intracerebral haemorrhage, with potential implications for antithrombotic treatment decisions. Thus, cortical superficial siderosis is of relevance to neurologists working in neurovascular, memory and epilepsy clinics, and neurovascular emergency services, emphasizing the need for appropriate blood-sensitive magnetic resonance sequences to be routinely acquired in these clinical settings. In this review we focus on recent developments in neuroimaging and detection, aetiology, prevalence, pathophysiology and clinical significance of cortical superficial siderosis, with a particular emphasis on cerebral amyloid angiopathy. We also highlight important areas for future investigation and propose standards for evaluating cortical superficial siderosis in research studies. PMID:26115675

  19. 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. PMID:20929114

  20. CLINICALLY SIGNIFICANT PSYCHOTROPIC DRUG-DRUG INTERACTIONS IN THE PRIMARY CARE SETTING

    PubMed Central

    English, Brett A.; Dortch, Marcus; Ereshefsky, Larry; Jhee, Stanford

    2014-01-01

    In recent years, the growing numbers of patients seeking care for a wide range of psychiatric illnesses in the primary care setting has resulted in an increase in the number of psychotropic medications prescribed. Along with the increased utilization of psychotropic medications, considerable variability is noted in the prescribing patterns of primary care providers and psychiatrists. Because psychiatric patients also suffer from a number of additional medical comorbidities, the increased utilization of psychotropic medications presents an elevated risk of clinically significant drug interactions in these patients. While life-threatening drug interactions are rare, clinically significant drug interactions impacting drug response or appearance of serious adverse drug reactions have been documented and can impact long-term outcomes. Additionally, the impact of genetic variability on the psychotropic drug’s pharmacodynamics and/or pharmacokinetics may further complicate drug therapy. Increased awareness of clinically relevant psychotropic drug interactions can aid clinicians to achieve optimal therapeutic outcomes in patients in the primary care setting. PMID:22707017

  1. Clinical significance of patterns of incidental thyroid uptake at (18)F-FDG PET/CT.

    PubMed

    Agrawal, K; Weaver, J; Ngu, R; Krishnamurthy Mohan, H

    2015-05-01

    Incidental uptake of 2-[(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) in the thyroid gland is not uncommonly encountered in day-to-day practice of oncological (18)F-FDG positron-emission tomography/computed tomography (PET/CT). These are often felt to be "nuisance lesions" by referring clinicians and radiologists alike. However, recognition of the importance of different patterns of FDG uptake in the thyroid gland and knowledge of the possible underlying aetiologies are crucial in ensuring that patients are managed appropriately in the clinical context of their primary diagnosis, as the underlying pathological condition may be clinically important in a significant minority of such cases. This review describes the various patterns of (18)F-FDG uptake within the thyroid and discusses the clinical significance and possible impact on patient management. Incidental low-grade homogeneous diffuse increased thyroid (18)F-FDG uptake is usually seen in the patients with chronic thyroiditis, Grave's disease, and hypothyroidism. Thyroid function tests and antibody profiling are advised in these patients. Incidental focal (18)F-FDG thyroid uptake should raise the possibility of underlying malignancy. Ultrasound with or without fine-needle aspiration cytology is usually recommended for the evaluation of these lesions. Heterogeneous uptake with prominent focal uptake in the thyroid should be further evaluated to exclude malignancy. PMID:25687827

  2. Two Functional Variants of IRF5 Influence the Development of Macular Edema in Patients with Non-Anterior Uveitis

    PubMed Central

    Cordero-Coma, Miguel; Ortego-Centeno, Norberto; Adán, Alfredo; Fonollosa, Alejandro; Díaz Valle, David; Pato, Esperanza; Blanco, Ricardo; Cañal, Joaquín; Díaz-Llopis, Manuel; de Ramón, Enrique; del Rio, María José; García Serrano, José Luis; Artaraz, Joseba; Martín-Villa, José Manuel; Llorenç, Víctor; Gorroño-Echebarría, Marina Begoña; Martín, Javier

    2013-01-01

    Objective Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes. Methods Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin. Results A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (PFDR=5.07E-03, OR=1.48, CI 95%=1.14-1.92 and PFDR=3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively). Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients. Conclusion Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies. PMID:24116155

  3. Clinical significance of B7-H6 protein expression in astrocytoma

    PubMed Central

    Guo, Jian-gui; Guo, Cheng-cheng; He, Zhen-qiang; Liu, Zhi-gang; Wang, Yang; Mou, Yong-gao

    2016-01-01

    Currently, immunotherapy by blocking the immune checkpoint inhibitors, such as anti-PD-1, has been carried out in many clinical studies on recurrent glioma, and the preliminary results are satisfactory, which provides a rationale for the exploration of immune checkpoint inhibitors in glioma. B7-H6 is a newly discovered member of the B7 family, which triggers antitumor of natural killer cell cytotoxicity and cytokine secretion by binding the NKp30 receptor. B7-H6 mRNA and protein expressions, which are not detected in normal tissues, are expressed mainly on the cell surface of various primary tumors and cell lines. However, up until now, there is no data about the clinical significance of B7-H6 expression in astrocytoma patients. The present study provides an investigation on the relationship between prognostic and clinical value of B7-H6 protein in astrocytoma tissues. All the astrocytic glioma tissues were stained for B7-H6. Immunohistochemistry stain of 122 astrocytoma samples showed that immunoreactivity of B7-H6 was seen predominantly in the cytoplasm. The B7-H6 expression did not show significant relevance with patient age, sex distribution, Karnofsky performance status score, extent of resection, and tumor location in astrocytoma patients, but B7-H6 positive expression is significantly associated with World Health Organization grade (P=0.046). However, the survival rate after operation presented no significant difference of B7-H6 expression in astrocytoma patients. Kaplan–Meier analysis and the log-rank test revealed that B7-H6 expression cannot predict the overall survival. In all, it seems that the B7-H6 expression might be a marker to differentiate the World Health Organization grade level of astrocytoma, but the prognosis value of B7-H6 in astrocytoma should be studied in detail. PMID:27330308

  4. Practice Guidelines for the Assessment of Clinically Significant Treatment Outcomes in the Children's Mental Health System.

    PubMed

    Chomycz, Suzanne; Schmidt, Fred

    2016-01-01

    The use of program evaluation to monitor client change and improve intervention effectiveness is gaining increasing importance in the mental health field. However, there is a lack of literature available in community-based clinics for those who desire to evaluate the effectiveness of services. Through this article the authors review the literature on the best methods to assess clinically significant treatment outcomes in community-based children's mental health services. The strengths and weaknesses of commonly recommended methods of evaluating change are discussed (i.e., reliable change index, percentage of improvement, normative comparisons, and effect size) using a dataset from a community-based parenting program (N = 308). PMID:26086975

  5. The clinical significance of autoantibodies to the proliferating cell nuclear antigen (PCNA).

    PubMed

    Mahler, Michael; Miyachi, Kiyomitsu; Peebles, Carol; Fritzler, Marvin J

    2012-08-01

    Autoantibodies targeting the proliferating cell nuclear antigen (PCNA) were first described over 30 years ago and are historically most commonly associated with systemic lupus erythematosus (SLE). The primary antigenic target is a 34 kDa protein that is part of the DNA polymerase delta multi-protein complex. A number of diagnostic platforms have incorporated PCNA into their diagnostic assays and algorithms. However, little is known about the clinical utility of autoantibodies to PCNA, especially with novel detection systems. This review will focus on the history of the discovery of the PCNA autoantigen and the current status of the diagnostic significance of anti-PCNA and suggest future studies that are required to strengthen our understanding of their clinical utility. PMID:22381917

  6. Disturbed eating behaviors and eating disorders in type 1 diabetes: clinical significance and treatment recommendations.

    PubMed

    Goebel-Fabbri, Ann E

    2009-04-01

    Girls and women with type 1 diabetes have increased rates of disturbed eating behaviors and clinically significant eating disorders than their nondiabetic peers. Type 1 diabetes is strongly associated with several empirically supported eating disorder risk factors (eg, higher body mass index, increased body weight and shape dissatisfaction, low self-esteem and depression, and dietary restraint). It may be that specific aspects of diabetes treatment increase the risk for developing disordered eating. Disturbed eating behaviors and clinical eating disorders predispose women with diabetes to many complex medical risks and increase risk of morbidity and mortality. For this reason, it is critical that diabetes clinicians understand more about eating disorders to improve the likelihood of early risk detection and access to appropriate treatment. This article presents a review of the current scientific literature on eating disturbances in type 1 diabetes and synthesizes the existent findings into recommendations for screening and treatment. PMID:19323958

  7. Clinical and prognostic significance of HIF-1α in glioma patients: a meta-analysis

    PubMed Central

    Liu, Qi; Cao, Peicheng

    2015-01-01

    Gliomas are the most common brain tumors, leading to significant cancer-related mortality worldwide. Hypoxia-inducible factor 1-alpha (HIF-1α) was shown to be involved in the pathophysiology and management of glioma, and might offer a therapeutic target. However, the results remain inconclusive. The purpose of this study was to systematically investigate the clinical and prognostic significance of HIF-1α expression in patients with glioma. Relevant studies published between 2000 and 2015 were searched in the electronic databases. The odds ratio (OR), risk ratio (RR) and mean difference (MD) with their 95% confidence intervals (CI) were employed to calculate the strength of significance. Finally, a total of 24 articles were retrieved, including 1422 glioma patients. No significant heterogeneity was presented between studies (I2<50%, P>0.01). Overall, our results showed that HIF-1α expression was significantly associated with high WHO grade (III+IV) of glioma (OR=8.59, 95% CI=6.56-11.24, P<0.00001). This significant relationship was also found between HIF-1α expression and microvascular density (MD=26.32, 95% CI=14.48-38.16, P<0.0001), overall survival (OS) (3-year OS: RR=0.48, 95% CI=0.35-0.66, P<0.00001; 2-year OS: RR=0.53, 95% CI=0.38-0.73, P<0.0001; 1-year OS: RR=0.79, 95% CI=0.66-0.95, P=0.01), and the cumulative survival time. However, HIF-1α expression was not associated with age and gender of glioma patients (P>0.05). In conclusions, our results suggested that HIF-1α expression was associated with high grade of glioma and OS, indicating that HIF-1α could predict prognosis and provide clinical insights into the therapeutic strategy for patients with glioma. More studies concerning other populations are also needed in the future research. PMID:26885182

  8. Incidental and Isolated Follicular Lymphoma In Situ and Mantle Cell Lymphoma In Situ Lack Clinical Significance.

    PubMed

    Bermudez, Glenda; González de Villambrosía, Sonia; Martínez-López, Azahara; Batlle, Ana; Revert-Arce, José B; Cereceda Company, Laura; Ortega Bezanilla, César; Piris, Miguel A; Montes-Moreno, Santiago

    2016-07-01

    Follicular lymphoma in situ (FLIS) and mantle cell lymphoma in situ (MCLIS) are histopathologic findings of undetermined clinical significance. We studied a series of 341 consecutive lymph node resection specimens from patients diagnosed with colorectal (201 cases) and breast (140 cases) adenocarcinoma between 1998 and 2000. Incidental and isolated FLIS was identified in 11/341 patients (3.23%), whereas incidental and isolated MCLIS was found in 2/341 patients (0.59%). None of these cases developed overt lymphoma. A second series of 17 cases of FLIS (16 cases) and MCLIS (1 case) from consultation files was analyzed. Five cases with incidental and isolated FLIS were identified. None of these cases developed overt lymphoma. Overall, none of the 16 cases with incidental and isolated FLIS in both series developed overt FL after a median follow-up of 54 months (range, 7 to 187 mo). However, 12 of these cases with a clinical suspicion of lymphoproliferative disorder showed the association (in different lymph nodes) or combination (in the same sample) of FLIS or MCLIS with other lymphoid neoplasms (FL, splenic marginal zone lymphoma, nodal marginal zone lymphoma, Hodgkin lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, multiple myeloma). In conclusion, the clinical relevance of FLIS and MCLIS seems to strictly depend on the clinical context. Incidental FLIS or MCLIS seem to have a very low risk for transformation, which recommends careful clinical examination after histopathologic diagnosis and conservative management with follow-up for a limited period of time. PMID:26945339

  9. Clinical Significance of Auditory Target P300 Subcomponents in Psychosis: Differential Diagnosis, Symptom Profiles, and Course

    PubMed Central

    Perlman, Greg; Foti, Dan; Jackson, Felicia; Kotov, Roman; Constantino, Eduardo; Hajcak, Greg

    2015-01-01

    Background Reduced auditory target P300 amplitude is a leading biomarker for psychotic disorders, although its relevance for differential diagnosis and link to specific clinical features (symptom profiles, functional impairment, and course) is unclear. This study aims to clarify the clinical significance of auditory target P300 using concurrent and retrospective clinical data from a longitudinal cohort with psychosis. Methods 92 cases from an epidemiological study of first-admission psychosis were assessed using an auditory oddball paradigm at 15-year follow-up along with 44 never-psychotic adults. Subcomponents of auditory target P300 amplitude (i.e., a central positive P3a, a parietal positive P3b, and a frontal negative slow wave) were isolated using temporal-spatial principal components analysis. Results P3a amplitude was blunted across psychotic disorders relative to non-psychotic adults. P3b amplitude was reduced in schizophrenia specifically, including cases initially misclassified at baseline. The frontal negative slow wave did not distinguish among groups. P3b amplitude reduction was associated with several clinical features at the concurrent assessment, as well as previous time points, including recovery from psychosis even 5 years earlier and functioning even 15 years earlier. Conclusions Auditory target P300 amplitude yields both a schizophrenia-specific component (i.e., P3b) and a transdiagnostic psychosis component (i.e., P3a). The P3b component may also shed light on prognosis, real-world functioning, and course, as well as help to reduce misdiagnosis of psychotic disorders. Prospective studies are needed to test whether P3b tracks or predicts clinical status. PMID:25934167

  10. 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:

  11. Clinical significance of serum protease-activated receptor-1 levels in gastric cancer patients

    PubMed Central

    TAS, FARUK; KARABULUT, SENEM; TASTEKIN, DIDEM; DURANYILDIZ, DERYA

    2016-01-01

    Protease-activated receptor-1 (PAR-1) has a significant role in the pathogenesis of various malignancies and its expression mainly affects the survivals of cancer patients. The aim of the present study was to determine the clinical significance of the serum concentrations of PAR-1 in patients with gastric carcinoma. A total of 63 pathologically confirmed gastric cancer patients were enrolled in this study, with a median age of 62 years. Serum PAR-1 concentrations were determined by the enzyme-linked immunosorbent assay method and no significant difference in the baseline serum PAR-1 concentrations was found between patients and normal controls (P=0.5). The investigated clinical variables, including patient age, gender, localization of lesion, histology, grade of pathology, disease stage and serum tumor markers (lactate dehydrogenase, carcinoembryonic antigen and carbohydrate antigen 19-9) were not correlated with serum PAR-1 levels (P>0.05). Furthermore, no association was identified between the serum PAR-1 level and chemotherapy responsiveness (P=0.43). Serum PAR-1 level also had no prognostic role for survival (P=0.27). In conclusion, the serum PAR-1 concentration has no diagnostic, predictive and prognostic values in gastric cancer patients. PMID:27073639

  12. 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

  13. 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

  14. [The pathogenetic and clinical significance of disorders in hemostatic homeostasis in diabetics].

    PubMed

    Lapchyns'ka, I I; Bielits'ka, H O; Kovalenko, S O

    1997-01-01

    DM patients who do not present with clinical manifestations of nephropathy exhibited significant reduction of urine fibrinolytic activity which is regarded as suggesting a preclinical stage of renal lesion in DM as well as hyperaggregation of platelets, enhanced activity of coagulative link of hemostasis and changes of different directions in the system of fibrinolysis. Among coagulologic methods, of most informative value is the turbidimetric method. In DM and low tolerability to glucosa, there is an increased incidence of gastroduodenal abnormalities, ulcer disease included, which fact warrants a gastroenterologic evaluation to be done in this patient population prior to prescribing anticoagulants. PMID:9491703

  15. The Clinical Significance and Potential Therapeutic Role of GPx3 in Tumor Recurrence after Liver Transplantation

    PubMed Central

    Qi, Xiang; Ng, Kevin Tak-Pan; Shao, Yan; Li, Chang Xian; Geng, Wei; Ling, Chang Chun; Ma, Yuen Yuen; Liu, Xiao Bing; Liu, Hui; Liu, Jiang; Yeung, Wai Ho; Lo, Chung Mau; Man, Kwan

    2016-01-01

    Background and Aims: Our previous study showed that small-for-size liver graft may provide favorable micro-environment for tumor growth. GPx3, an anti-oxidant, not only attenuates oxidative stress, but also suppresses liver tumor growth in our recent study. Here, we aimed to characterize the clinical significance and explore the functional role of GPx3 in HCC recurrence after liver transplantation. Methods: To explore the association between GPx3 expression and HCC invasiveness, a rat orthotopic liver transplantation model with tumor development was established. To investigate the clinical relevance of GPx3, 105 HCC patients who underwent liver transplantation were recruited. The suppressive role of GPx3 in HCC cells was studied using wound healing, Matrigel invasion assay and lung metastasis model. The real-time intravital imaging system was applied to directly visualize the tumor cells invasion in a living animal. The underlying mechanism was further explored. Results: GPx3 was identified as a down-regulated protein in small-for-size liver graft and significantly associated with invasive phenotype of tumor growth in a rat model. Plasma GPx3 was significantly lower in small-for-size graft group post-transplantation (day1: 33 vs 1147; day3: 3209 vs 4459; day7: 303 vs 2506; mU/mL, P<0.05) in rat model. Clinically, the plasma GPx3 was significantly lower in the recipients with HCC recurrence post-transplantation (day1: 4.16 vs 8.99 µg/mL, P<0.001; day7: 3.86 vs 9.99 µg/mL, P<0.001). Furthermore, lower plasma GPx3 was identified as an independent predictor (HR=4.528, P=0.046) for poor overall survival post-transplantation. Over-expression of GPx3 significantly suppressed migration, invasiveness and metastasis of HCC cells. Real-time intravital imaging showed that GPx3 significantly suppressed HCC invasiveness in a live animal. GPx3 suppressed the tumor invasiveness through inhibition of JNK-cJun-MMP2 pathway. Conclusion: GPx3 may possess prognostic and therapeutic

  16. Angiostrongylus cantonensis: a review of its distribution, molecular biology and clinical significance as a human pathogen.

    PubMed

    Barratt, Joel; Chan, Douglas; Sandaradura, Indy; Malik, Richard; Spielman, Derek; Lee, Rogan; Marriott, Deborah; Harkness, John; Ellis, John; Stark, Damien

    2016-08-01

    Angiostrongylus cantonensis is a metastrongyloid nematode found widely in the Asia-Pacific region, and the aetiological agent of angiostrongyliasis; a disease characterized by eosinophilic meningitis. Rattus rats are definitive hosts of A. cantonensis, while intermediate hosts include terrestrial and aquatic molluscs. Humans are dead-end hosts that usually become infected upon ingestion of infected molluscs. A presumptive diagnosis is often made based on clinical features, a history of mollusc consumption, eosinophilic pleocytosis in cerebral spinal fluid, and advanced imaging such as computed tomography. Serological tests are available for angiostrongyliasis, though many tests are still under development. While there is no treatment consensus, therapy often includes a combination of anthelmintics and corticosteroids. Angiostrongyliasis is relatively rare, but is often associated with morbidity and sometimes mortality. Recent reports suggest the parasites' range is increasing, leading to fatalities in regions previously considered Angiostrongylus-free, and sometimes, delayed diagnosis in newly invaded regions. Increased awareness of angiostrongyliasis would facilitate rapid diagnosis and improved clinical outcomes. This paper summarizes knowledge on the parasites' life cycle, clinical aspects and epidemiology. The molecular biology of Angiostrongylus spp. is also discussed. Attention is paid to the significance of angiostrongyliasis in Australia, given the recent severe cases reported from the Sydney region. PMID:27225800

  17. 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

  18. The clinical significance of dipstick-negative, culture-positive urines in a veterans population.

    PubMed

    Gutman, S I; Solomon, R R

    1987-08-01

    The consequences of omitting cultures in dipstick-negative urines submitted to the authors' microbiology laboratory were evaluated retrospectively in 1,079 clean-catch midstream samples. Using positive dipstick readings for leukocyte esterase, nitrite, and/or protein as evidence of a positive screen, the sensitivity, specificity, positive predictive value, and negative predictive value for specimens containing more than or 10(3) CFUs/mL (10(6)/L) were 80%, 71%, 48%, and 91%, respectively. Clinical data were reviewed in 38 patients with one or more dipstick-negative, culture-positive urines. Most of these patients lacked clinical or other laboratory evidence suggesting urinary tract infection. Problems with specimen collection were suspected in 19 neurologically compromised patients. Only two patients with dipstick-negative urines received treatment based on the culture reports. Symptoms persisted in both. The authors conclude that in their predominantly male veteran population, clinically significant bacteriuria is an unlikely finding in a dipstick-negative urine. PMID:3618553

  19. Detection methods and clinical significance of free peritoneal tumor cells found during colorectal cancer surgery

    PubMed Central

    Sibio, Simone; Fiorani, Cristina; Stolfi, Carmine; Divizia, Andrea; Pezzuto, Roberto; Montagnese, Fabrizio; Bagaglini, Giulia; Sammartino, Paolo; Sica, Giuseppe Sigismondo

    2015-01-01

    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. PMID:26425265

  20. 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. PMID:27135623

  1. Clinical significance of surgical margin status in patients subjected to radical prostatectomy.

    PubMed

    Dobruch, Jakub; Nyk, Lukasz; Skrzypczyk, Michał; Chłosta, Piotr; Dzik, Tomasz; Borówka, Andrzej

    2012-01-01

    The aim of this study is to evaluate the clinical value of positive surgical margins (PSM) in patients subjected to radical prostatectomy (RP). The data of men who were subjected to RP from the 1st of January, 2001 to the 30th of May, 2010 were analyzed. Specimens with PSM were again evaluated to confirm the presence of positive margins. PSM were found in 64 (25%) out of 255 analyzed patients. Out of all clinical features, only biopsy Gleason score and clinical stage of the disease were found to be predictive of PSM. Biochemical recurrence (BR) was found in 42 (16.5%) men, among them 17 (26.6%) had PSM and 25 (13.1%) had negative margins. The risk of BR in those with "focal" PSM (<3 mm) did not differ from the risk of BR observed in patients without PSM. In contrast, the likelihood of BR was significantly greater in cases of PSM in which maximum longitude exceeded 3 mm. Reevaluation of the PSM specimens revealed equivocal margins status in six cases. PSM are not inevitably associated with BR. The risk of failure is influenced by their length. Reevaluation of the prostate specimen may lead to surgical margins status modification. PMID:24578961

  2. 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

  3. Guided self-help CBT treatment for bulimic disorders: effectiveness and clinically significant change.

    PubMed

    Vaz, Ana Rita; Conceição, Eva; Machado, Paulo P P

    2013-01-01

    The aim of this study was to test the effectiveness of a cognitive-behavioral guided self-help treatment program for bulimia nervosa and similar disorders. Participants were assessed at the beginning and end of treatment, and at 6 months follow-up, using the Eating Disorder Examination Questionnaire (EDE-Q), the Outcome-Questionnaire-45 (OQ-45), and the Beck Depression Inventory (BDI). Forty-two participants from an eating disorders treatment service participated in this study. This study followed a one-group repeated measures naturalistic design with no control group. Results showed a significant reduction in EDE scores, OQ-45 and BDI. Clinically significant change occurred for the majority of participants. Cognitive-behavioral self-help treatment may be of value as an initial treatment for bulimia nervosa and similar disorders such as binge eating disorder. PMID:23701428

  4. Multiple mechanisms contribute to the development of clinically significant azole resistance in Aspergillus fumigatus

    PubMed Central

    Moye-Rowley, W. S.

    2015-01-01

    Infections caused by the filamentous fungus Aspergillus fumigatus are a significant clinical issue and represent the second most-common form of fungal infection. Azole drugs are effective against this pathogen but resistant isolates are being found more frequently. Infections associated with azole resistant A. fumigatus have a significantly increased mortality making understanding drug resistance in this organism a priority. The target of azole drugs is the lanosterol α-14 demethylase enzyme encoded by the cyp51A gene in A. fumigatus. Mutations in cyp51A have been described that give rise to azole resistance and been argued to be the primary, if not sole, contributor to azole resistance. Here, I discuss recent developments that indicate multiple mechanisms, including increased expression of ATP-binding cassette (ABC) transporter proteins, contribute to azole resistance. ABC transporters are well-established determinants of drug resistance in other fungal pathogens and seem likely to play a similar role in A. fumigatus. PMID:25713565

  5. The Clinical Significance of HbA1c in Operable Chronic Thromboembolic Pulmonary Hypertension

    PubMed Central

    Richter, Manuel Jonas; Milger, Katrin; Haase, Sarah; Sommer, Natascha; Tello, Khodr; Seeger, Werner; Mayer, Eckhard; Wiedenroth, Christoph Benjamin; Grimminger, Friedrich; George, Wolfgang; Ghofrani, Hossein Ardeschir; Guth, Stefan; Gall, Henning

    2016-01-01

    Background Glycosylated hemoglobin A1c (HbA1c) has been proposed as an independent predictor of long-term prognosis in pulmonary arterial hypertension. However, the clinical relevance of HbA1c in patients with operable chronic thromboembolic pulmonary hypertension (CTEPH) remains unknown. The aim of the present study was to investigate the clinical significance of HbA1c as a biomarker in CTEPH. Methods Prospectively, 102 patients underwent pulmonary endarterectomy (PEA) in our national referral center between March 2013 and March 2014, of which after exclusion 45 patients were analyzed. HbA1c- levels, hemodynamic and exercise parameters were analyzed prior and one-year post-PEA. Results 45 patients (BMI: 27.3 ± 6.0 kg/m2; age: 62.7 ± 12.3 years) with a mean pulmonary arterial pressure (mPAP) of 43.6 ± 9.4 mmHg, a pulmonary vascular resistance (PVR) of 712.1 ± 520.4 dyn*s/cm5, a cardiac index (CI) of 2.4 ± 0.5 l/min/m2 and a mean HbA1c-level of 39.8 ± 5.6 mmol/mol were included. One-year post-PEA pulmonary hemodynamic and functional status significantly improved in our cohort. Baseline HbA1c-levels were significantly associated with CI, right atrial pressure, peak oxygen uptake and the change of 6-minute walking distance using linear regression analysis. However, using logistic regression analysis baseline HbA1c-levels were not significantly associated with residual post-PEA PH. Conclusions This is the first prospective study to describe an association of HbA1c-levels with pulmonary hemodynamics and exercise capacity in operable CTEPH patients. Our preliminary results indicate that in these patients impaired glucose metabolism as assessed by HbA1c is of clinical significance. However, HbA1c failed as a predictor of the hemodynamic outcome one-year post-PEA. PMID:27031508

  6. Difference, significant difference and clinically meaningful difference: The meaning of change in rehabilitation

    PubMed Central

    Dvir, Zeevi

    2015-01-01

    The valid confirmation of a positive change (improvement) in a patient’s health status due to intervention has been at the core of medicine and rehabilitation since their very inception as clinicians always aspired to ensure that treating their patients had led to successful outcomes both in acute and chronic conditions. However what is change: either improvement or worsening (aggravation), is a complicated issue which involves clinical as well as statistical considerations. Change invariably relates to a difference in some measurable entity and almost always it relates to a time span. The confirmation of clinical change is important both for varying the treatment course (if necessary) and for the termination of treatment when the latter has reached wither its prescribed objective or a plateau. Since in the context of rehabilitation, the outcome measures (OM) are strongly linked to performance, determination of change in the latter is confounded by many factors, collectively known as the error of measurement, which render a decision regarding clinically meaningful change, highly involved. This is further complicated by the stability of the observed OM, the so-called reproducibility of the OM, and the accuracy of the measurement instrument. The higher the reproducibility the lower is the error. Moreover, in order to proclaim change, in most cases a positive one, it is necessary for the difference in outcome scores (i.e. the change) to surpass the error of measurement, in varying degree of rigor. This paper describes selected methods associated with determination of change and focuses predominantly on the difference between a simple difference in scores (‘simple change’), a significant difference in scores and the so-called clinically meaningful change in scores which is considered today as the benchmark for confirmation of a real change. PMID:25960978

  7. Posterior cerebral artery--variation in the origin and clinical significance.

    PubMed

    Dodevski, Ace; Tosovska Lazarova, Dobrila; Mitreska, Nadica; Aliji, Vjolca; Stojovska Jovanovska, Elizabeta

    2014-01-01

    With the introduction of new techniques in diagnostic and interventional radiology and progress in micro-neurosurgery, accurate knowledge of the brain blood vessels is essential in daily clinical work. The aim of this study was to describe the different types of PCA origin, their diameter, and to emphasize their clinical significance. In this study we examined radiographs of 53 patients who had CT angiography undertaken for a variety of clinical reasons, performed as a part of their medical treatment at the University Radiology Clinic in Skopje, R. Macedonia. This study included 24 females and 29 males, ranging in age from 32 to 73 years; mean age 55.3±11.5 years. The results showed that the diameter of the posterior cerebral artery was 1.74±0.317 mm on the right side and 1.98±0.408 mm on the left side. The adult configuration was present in 37 (69.81%); foetal configuration was present in 12 (22.64%) and transitional configuration was present in 4 (7.54%) of the patients. We found two patients with bilateral foetal type and ten with unilateral foetal type (six on the right side and four on the left side). Despite the limitations of the study, we found that the foetal variant was presented in 22.64% of patients. Thorough knowledge of the anatomy of the intracranial vessels is important to clinicians as well as basic scientists who deal with problems related to intracranial vasculature on a daily basis. PMID:24798602

  8. Clinical, Functional and Health-Related Quality of Life Correlates of Clinically Significant Symptoms of Anxiety and Depression in Patients with Systemic Sclerosis: A Cross-Sectional Survey

    PubMed Central

    Nguyen, Christelle; Ranque, Brigitte; Baubet, Thierry; Bérezné, Alice; Mestre-Stanislas, Caroline; Rannou, François; Papelard, Agathe; Morell-Dubois, Sandrine; Revel, Michel; Moro, Marie-Rose; Guillevin, Loïc; Poiraudeau, Serge; Mouthon, Luc

    2014-01-01

    Objectives To identify clinical, functional and health-related quality of life (HRQoL) correlates of clinically significant symptoms of anxiety and depression in patients with systemic sclerosis (SSc). Methods Three-hundred-and-eighty-one patients fulfilling the American College of Rheumatology and/or the Leroy and Medsger criteria for SSc were assessed for visceral involvement, disability and HRQoL (assessed by SF-36). Clinically significant symptoms of anxiety and depression were evaluated with the Hospital Anxiety Depression Scale (HAD) (defined cut-off≥8). Results 9.2% the patients had limited SSc, 50.5% limited cutaneous SSc (lcSSc), and 40.3% diffuse cutaneous SSc (dcSSc). Overall, 40.4% and 58.8% of the patients had clinically significant symptoms of depression and anxiety, respectively. Compared to patients without clinically significant symptoms of depression, patients with clinically significant symptoms of depression had poorer health status, HRQoL mental and physical component, and greater global disability, hand disability and aesthetic impairment. Compared to patients without clinically significant symptoms of anxiety, patients with clinically significant symptoms of anxiety had poorer SF-36 mental and physical component scores. On multivariable analysis, excluding mental component score of SF-36, variables independently associated with clinically significant symptoms of depression and anxiety were global disability and physical component of SF-36, plus female gender for clinically significant symptoms of anxiety only. Remarkably, patients with and without clinically significant psychiatric symptoms were comparable for all disease-related clinical features assessed. Conclusion High levels of clinically significant symptoms of anxiety and depression are observed among SSc patients. Clinically significant psychiatric symptoms are rather associated with increased disability and altered HRQoL, than with disease-specific organ manifestations. PMID

  9. Relevance and clinical significance of serum resistin level in obese T2DM rhesus monkey models.

    PubMed

    Qi, S-D; He, Z-L; Chen, Y; Ma, J; Yu, W-H; Li, Y-Y; Yang, F-M; Wang, J-B; Chen, L-X; Zhao, Y; Lu, S-Y

    2015-09-01

    Resistin is a type of hormone-like adipocytokines, which is secreted specifically by adipocytes. It may be a key factor in the development of type 2 diabetes mellitus (T2DM) from obesity- associated insulin resistance due to results that show that it has a close relationship with insulin resistance in rodents. We utilized the rhesus monkeys as study objects to preliminarily test the association with glucose metabolism and to conduct a correlation analysis for clinical parameters and serum resistin levels in obese rhesus monkey models of T2DM. The results suggested that resistin was significantly increased in T2DM monkeys (P <0.01), and that resistin had a positive correlation respectively with total cholesterol (TC), low-density lipoprotein (LDL-C), fasting plasma glucose (FPG), fasting insulin (FPI) and glycated hemoglobin (HbA1c), Insulin resistance index (HOA-IR), but a negative correlation with islet β-cell function (HOMA-β). In the course of glucose metabolism, reverse release change of resistin and insulin in T2DM monkeys occurred, but the phenomenon that was not observed in the control group, these findings indicated that resistin negatively regulated and interfered with carbohydrate metabolism in T2DM monkey models. The character of the releasing change of resistin might be a unique process in T2DM. Therefore, all of the results could provide references for clinical diagnostic criteria for human cases of T2DM, and could have clinical significance for obese T2DM diagnosis and degree of insulin resistance. PMID:26069076

  10. Clinical significance of programmed death ligand-1 (PD-L1) in colorectal serrated adenocarcinoma

    PubMed Central

    Zhu, Hailong; Qin, Huali; Huang, Ziling; Li, Shuai; Zhu, Xuyou; He, Jian; Yang, Jing; Yu, Xiaoting; Yi, Xianghua

    2015-01-01

    Preliminary research results with antibody of the negative costimulatory molecule programmed cell death ligand-1 (PD-L1) suggested its expression on tumor cells associated with various tumor grade and postoperative prognosis. However, to date, there is no information of PD-L1 expression in colorectal serrated adenocarcinoma (SAC) and its clinical relevance. Therefore, the purpose of this study is to investigate the clinical significance of PD-L1 expression in a large cohort of patients with SAC. Here, we first retrospectively identified all SAC collected at our institution between August 2008 and May 2013. The expression levels of PD-L1 were examined by immunohistochemistry in 120 patients with SAC. We further evaluated the correlation between expression data and clinical parameters, including patient age, sex, tumor size, location, grade, primary tumor classification (pT), lymph node metastasis (pN), distant metastases (pM), and vascular invasion. Strong PD-L1 expression was detected in 25% of SAC. Higher expression of PD-L1 was significantly associated with pN (P=0.003) and pM (P=0.014). Survival analysis showed that patients with higher expression of PD-L1 had a poorer prognosis (P=0.045). However, multivariate regression analysis did not support PD-L1 as an independent prognostic factor (P=0.430). Our data suggest that PD-L1 may represent a new biomarker of metastasis and prognosis for patients with SAC, but as a target in the treatment of SAC is less certain. PMID:26464688

  11. 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

  12. Frequency and clinical significance of placental histological lesions in an unselected population at or near term.

    PubMed

    Pathak, Sangeeta; Lees, Christoph C; Hackett, Gerald; Jessop, Flora; Sebire, Neil J

    2011-12-01

    Associations between specific placental histological abnormalities and obstetric outcomes are reported. However, most data are based either on high-risk cases or relate to case-control studies selected from those with abnormal placental histology findings, with the unavoidable biases that these approaches entail. This study reports the frequency of the several common, objective and predefined histological abnormalities of the placenta as identified by pathologists blinded to all clinical information. A total 1,153 women were recruited from an unselected population delivering at 34-43 weeks. Histological findings in common obstetric outcome groups were compared to those of the unselected population, and odds ratios and predictive values were calculated. Normal histological findings were present in 72.1% of pregnancies with normal outcomes and in 79.1%, 66.6%, 80%, and 74.8% of pregnancies affected by pre-eclampsia (PET), pregnancy-induced hypertension (PIH), gestational diabetes (GDM), and small for gestational age (SGA), respectively. Chronic placental underperfusion was seen more frequently in PIH (odds ratio (OR) 2) and SGA (OR 1.4), while villitis of unknown aetiology was observed more commonly in cases with PIH (OR 3.2). Fetal thrombotic vasculopathy was twice as common in cases with GDM whilst massive perivillous fibrin deposition was much more frequent in those with PET (OR 20.2) and SGA (OR 8.9). Chorangiomata were 13 times more common in pregnancies with PET. However, in all cases, positive predictive values were low, with the majority of cases with histological abnormalities being associated with normal outcome. At term, specific placental histological lesions are significantly more common in complicated pregnancies, but the clinical significance of such lesions in a specific case remains uncertain, since the majority will be identified from clinically uncomplicated normal pregnancies. PMID:22038509

  13. 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

  14. 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. PMID:26354809

  15. Clinical Significance and Characterization of Streptococcus tigurinus Isolates in an Adult Population

    PubMed Central

    Bourassa, Lori

    2015-01-01

    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. PMID:26354809

  16. Expression of endothelin-1 in laryngocarcinoma tissues and its clinical significance

    PubMed Central

    WANG, SHAOZHONG; WU, JIAN; SONG, YISA; ZHONG, HUILING

    2016-01-01

    In recent years, the incidence of laryngeal carcinoma has been on the increase. The aim of the present study was to examine the expression level of endothelin-1 (ET-1) in laryngeal carcinoma tissues and to establish its clinical significance. A total of 82 cases of laryngeal carcinoma tissues were examined, of which 27 cases were stage I, 34 were stage II, and 21 were stage III. The normal mucosal tissues beyond the surgical incision margin in the 82 laryngeal carcinoma patients were used as the normal control. An additional 80 tissue specimens collected from laryngeal carcinoma outpatients were used as benign lesions. ET-1 expression levels in different tissues were determined using streptavidin-peroxidase (SP) immunohistochemistry. The results showed that the ET-1 expression level was highest in laryngeal carcinoma tissues and was significantly higher than that in the other two groups (P<0.05). The ET-1 expression level was higher in stage III compared to that in stage I and II (P<0.05) and higher than that of the normal control (P<0.05). The ET-1 expression level was higher in stage II compared to that in stage I (P<0.05). In conclusion, ET-1 was strongly expressed in laryngeal carcinoma tissues and may play an important role in the pathogenesis and development of laryngeal carcinoma tissues. ET-1 expression in laryngeal carcinoma tissues was associated with the clinical staging of laryngeal carcinoma. PMID:27123118

  17. Classical and Novel Prognostic Markers for Breast Cancer and their Clinical Significance

    PubMed Central

    Taneja, Pankaj; Maglic, Dejan; Kai, Fumitake; Zhu, Sinan; Kendig, Robert D.; Fry, Elizabeth A.; Inoue, Kazushi

    2010-01-01

    The use of biomarkers ensures breast cancer patients receive optimal treatment. Established biomarkers such as estrogen receptor (ER) and progesterone receptor (PR) have been playing significant roles in the selection and management of patients for endocrine therapy. HER2 is a strong predictor of response to trastuzumab. Recently, the roles of ER as a negative and HER2 as a positive indicator for chemotherapy have been established. Ki67 has traditionally been recognized as a poor prognostic factor, but recent studies suggest that measurement of Ki67-positive cells during treatment will more effectively predict treatment efficacy for both anti-hormonal and chemotherapy. p53 mutations are found in 20–35% of human breast cancers and are associated with aggressive disease with poor clinical outcome when the DNA-binding domain is mutated. The utility of cyclin D1 as a predictor of breast cancer prognosis is controversial, but cyclin D1b overexpression is associated with poor prognosis. Likewise, overexpression of the low molecular weight form of cyclin E1 protein predicts poor prognosis. Breast cancers from BRCA1/2 carriers often show high nuclear grades, negativity to ER/PR/HER2, and p53 mutations, and thus, are associated with poor prognosis. The prognostic values of other molecular markers, such as p14ARF, TBX2/3, VEGF in breast cancer are also discussed. Careful evaluation of these biomarkers with current treatment modality is required to determine whether their measurement or monitoring offer significant clinical benefits. PMID:20567632

  18. Statistical controversies in clinical research: statistical significance-too much of a good thing ….

    PubMed

    Buyse, M; Hurvitz, S A; Andre, F; Jiang, Z; Burris, H A; Toi, M; Eiermann, W; Lindsay, M-A; Slamon, D

    2016-05-01

    The use and interpretation of P values is a matter of debate in applied research. We argue that P values are useful as a pragmatic guide to interpret the results of a clinical trial, not as a strict binary boundary that separates real treatment effects from lack thereof. We illustrate our point using the result of BOLERO-1, a randomized, double-blind trial evaluating the efficacy and safety of adding everolimus to trastuzumab and paclitaxel as first-line therapy for HER2+ advanced breast cancer. In this trial, the benefit of everolimus was seen only in the predefined subset of patients with hormone receptor-negative breast cancer at baseline (progression-free survival hazard ratio = 0.66, P = 0.0049). A strict interpretation of this finding, based on complex 'alpha splitting' rules to assess statistical significance, led to the conclusion that the benefit of everolimus was not statistically significant either overall or in the subset. We contend that this interpretation does not do justice to the data, and we argue that the benefit of everolimus in hormone receptor-negative breast cancer is both statistically compelling and clinically relevant. PMID:26861602

  19. 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

  20. Expression of AQP5 and AQP8 in human colorectal carcinoma and their clinical significance

    PubMed Central

    2012-01-01

    Background The aquaporins (AQPs) are a family of small membrane transport proteins whose overexpression has been implicated in tumorigenesis. However, the expression of AQP5 and AQP8 in colorectal cancer and the clinical significance remain unexplored. This study aimed to detect the expression of AQP5 and AQP8 in clinical samples of colorectal cancer and analyze the correlations of their expression with the clinicopathological features of colorectal cancer. Methods Forty pairs of colorectal cancer tissue and paraneoplastic normal tissue were obtained at the time of surgery from patients with colorectal cancer. The expression of AQP5 and AQP8 was detected by immunohistochemical staining and reverse transcriptase polymerase chain reaction. Results AQP5 was mainly expressed in colorectal carcinoma cells and barely expressed in paraneoplastic normal tissues. By contrast, AQP8 was mainly expressed in paraneoplastic normal tissues and barely expressed in colorectal carcinoma cells. AQP5 expression was not significantly associated with the sex or age of the patient with colorectal cancer (P>0.05), but was closely associated with the differentiation, tumor-nodes-metastasis stage and distant lymph node metastasis of colorectal carcinoma (P<0.05). Conclusions AQP5 might be a novel prognostic biomarker for patients with colorectal cancer. PMID:23148732

  1. Combination of vascular endothelial growth factor inhibitors and laser therapy for diabetic macular oedema: a review.

    PubMed

    Mehta, Hemal; Gillies, Mark C; Fraser-Bell, Samantha

    2016-05-01

    This review provides a perspective on published and ongoing clinical trials of vascular endothelial growth factor inhibitors (anti-VEGF agents) combined with laser therapy for diabetic macular oedema (DMO). Although there was little short-term benefit in combining prompt macular laser with anti-VEGF therapy for centre-involving DMO in the Diabetic Retinopathy Clinical Research Network (DRCRnet) Protocol I study, deferred macular laser was still required in over 40% of study eyes in DRCRnet Protocol T. Macular laser was applied in more than 30% of eyes with centre-involving DMO receiving ranibizumab in the RISE and RIDE studies. For non centre-involving DMO the evidence-base still supports use of focal macular laser alone, although clinicians should be cautious about applying laser too close to the foveal avascular zone with the availability of pharmacotherapy. Ongoing clinical trials are assessing whether selectively targeting areas of peripheral retinal ischaemia with laser reduces the number of anti-VEGF injections to stabilise DMO and whether combining macular micropulse laser with anti-VEGF therapy is beneficial in DMO. PMID:27061760

  2. 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. PMID:27140751

  3. 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.

  4. Clinical significance of Gremlin 1 in cervical cancer and its effects on cancer stem cell maintenance.

    PubMed

    Sato, Masakazu; Kawana, Kei; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Takahashi, Juri; Adachi, Katsuyuki; Nagasaka, Kazunori; Matsumoto, Yoko; Wada-Hiraike, Osamu; Oda, Katsutoshi; Osuga, Yutaka; Fujii, Tomoyuki

    2016-01-01

    Gremlin 1 is one of the bone morphogenetic protein (BMP) antagonists and is also related to differentiation in combination with BMPs and is associated with various types of diseases. Gremlin 1 is overexpressed in various types of human cancers and has been reported to play a role in cervical cancer oncogenesis. However, there is no report concerning the relationship between Gremlin 1 and cervical cancer stem cells (CSCs). The objective of the present study was to identify the clinical significance of Gremlin 1 in cervical cancer and its effects on CSC-like properties in vitro. Clinical samples were obtained. Gremlin 1 mRNA expression levels in the cervical cancer tissues were measured by RT-qPCR and assessed for correlation with their clinical prognosis [overall survival (OS), progression-free survival (PFS)] and with other prognostic factors. In vitro, cervical cancer, CaSki cells, exposed to Gremlin 1 (1,000 ng/ml) for 24 h were evaluated for expression of undifferentiated-cell markers (Nanog, Oct3/4, Sox2) by RT-qPCR, the population of ALDH-positive cells by flow cytometry and sphere-forming ability on a ultra-low attachment culture dish. Cervical cancer tissues from 104 patients were collected. A high mRNA expression level of Gremlin 1 was an independent poor prognostic factor of PFS but not of OS. A high mRNA expression level of Gremlin 1 was correlated with bulky (>4 cm) tumors. The Nanog mRNA expression level was significantly increased in the CaSki cells exposed to Gremlin 1 (P=0.0008) but not Oct3/4 and Sox2 mRNA expression levels. The population of ALDH-positive cells in the Gremlin 1-exposed cells was 1.41-fold higher compared with the control (P=0.0184). Sphere-forming ability was increased when 1,000 Gremlin 1-exposed cells were seeded (P=0.0379). In cervical cancer, it is suggested that Gremlin 1 may have a role in clinical recurrence and maintaining CSC-like properties. PMID:26530461

  5. Frequency, Types, and Potential Clinical Significance of Medication-Dispensing Errors

    PubMed Central

    Bohand, Xavier; Simon, Laurent; Perrier, Eric; Mullot, Hélène; Lefeuvre, Leslie; Plotton, Christian

    2009-01-01

    INTRODUCTION AND OBJECTIVES: Many dispensing errors occur in the hospital, and these can endanger patients. The purpose of this study was to assess the rate of dispensing errors by a unit dose drug dispensing system, to categorize the most frequent types of errors, and to evaluate their potential clinical significance. METHODS: A prospective study using a direct observation method to detect medication-dispensing errors was used. From March 2007 to April 2007, “errors detected by pharmacists” and “errors detected by nurses” were recorded under six categories: unauthorized drug, incorrect form of drug, improper dose, omission, incorrect time, and deteriorated drug errors. The potential clinical significance of the “errors detected by nurses” was evaluated. RESULTS: Among the 734 filled medication cassettes, 179 errors were detected corresponding to a total of 7249 correctly fulfilled and omitted unit doses. An overall error rate of 2.5% was found. Errors detected by pharmacists and nurses represented 155 (86.6%) and 24 (13.4%) of the 179 errors, respectively. The most frequent types of errors were improper dose (n = 57, 31.8%) and omission (n = 54, 30.2%). Nearly 45% of the 24 errors detected by nurses had the potential to cause a significant (n = 7, 29.2%) or serious (n = 4, 16.6%) adverse drug event. CONCLUSIONS: Even if none of the errors reached the patients in this study, a 2.5% error rate indicates the need for improving the unit dose drug-dispensing system. Furthermore, it is almost certain that this study failed to detect some medication errors, further arguing for strategies to prevent their recurrence. PMID:19142545

  6. 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. PMID:26252284

  7. Clinical significance of serum cytokine levels and thrombopoietic markers in childhood idiopathic thrombocytopenic purpura

    PubMed Central

    Del Vecchio, Giovanni Carlo; Giordano, Paola; Tesse, Riccardina; Piacente, Laura; Altomare, Maria; De Mattia, Domenico

    2012-01-01

    Background Biological markers useful for defining children with newly diagnosed immune thrombocytopenic purpura (ITP) who are likely to develop the chronic form of the disease are partially lacking. The purpose of this study was to assess the clinical role of both immunological and thrombopoietic markers in children with ITP and correlate their levels with different disease stages. Materials and methods We enrolled 28 children with ITP at the onset of their disease, who were followed-up for a whole year and divided according to whether their disease resolved within the 12 months (n=13) or became chronic (n=15), 11 subjects with chronic ITP off therapy for at least 1 month at the time of enrolment, and 30 healthy matched controls. Serum levels of T helper type 1 and 2 and T regulatory-associated cytokines, such as interferon γ, tumour necrosis factor α, interleukin (IL) 2, IL6, IL10, and thrombopoietin were measured in all children using quantitative immunoenzymatic assays, while reticulated platelets were evaluated by flow cytometric analysis. Results Serum IL10 levels were significantly higher in patients with an acute evolution of ITP than in either healthy controls (p<0.001) or patients with chronic progression of ITP (p<0.05). Reticulated platelet count and thrombopoietin levels were significantly higher in ITP patients at the onset of their disease, whether with acute resolution or chronic progression, than in healthy subjects (p<0.01; p<0.001), but did not differ between the groups of patients. Conclusion IL-10 seems to predict the clinical course of ITP, as it is significantly higher at the onset of disease in patients who obtain disease remission in less than 1 year. PMID:22153687

  8. Clinical significance of thymidine kinase in Egyptian children with acute lymphoblastic leukemia

    PubMed Central

    Hagag, Adel A.; Saad, Mohamed A.; Mohamed, Sohair A.

    2015-01-01

    Background: Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, representing one-third of pediatric cancers. Thymidine kinase-1 (TK-1) is expressed in proliferating cells so elevated TK-1 indicates active tumor growth. Objective: To study the clinical significance of TK-1 in children with ALL. Patients and Methods: This study was carried out on 40 children with newly diagnosed ALL who were admitted to Oncology Unit, Pediatric department, Tanta University (26 males and 14 females) with their ages ranged from 4 to 10 years and 30 healthy children of matched age and sex as a control group. For all patients the following were done: Complete blood picture, bone marrow examination, immunophenotyping and TK-1 serum levels. Results: Mean TK-1 level was significantly higher in patients at diagnosis than controls and significantly higher in patients with unfavorable outcome than patients with favorable outcome. Mean TK-1 level was significantly higher in patients in relapse than patients in remission and controls. No significant differences in mean TK-1 level between patients in remission and controls. There were statistically significant differences in disease free survival and overall survival between patients with favorable and unfavorable outcome. Conclusion: From this study we concluded that TK is a helpful marker in diagnosis and follow-up of patients with ALL. Recommendations: Thymidine kinase-1 should be routinely assessed at diagnosis and during follow-up in ALL patients for better diagnostic and prognostic assessment and should be taken in consideration in designing future therapeutic strategies based on patients-specific risk factors. PMID:25992345

  9. The Effect of Modified Eggs and an Egg-Yolk Based Beverage on Serum Lutein and Zeaxanthin Concentrations and Macular Pigment Optical Density: Results from a Randomized Trial

    PubMed Central

    Kelly, Elton R.; Plat, Jogchum; Haenen, Guido R. M. M.; Kijlstra, Aize; Berendschot, Tos T. J. M.

    2014-01-01

    Increasing evidence suggests a beneficial effect of lutein and zeaxanthin on the progression of age-related macular degeneration. The aim of this study was to investigate the effect of lutein or zeaxanthin enriched eggs or a lutein enriched egg-yolk based buttermilk beverage on serum lutein and zeaxanthin concentrations and macular pigment levels. Naturally enriched eggs were made by increasing the levels of the xanthophylls lutein and zeaxanthin in the feed given to laying hens. One hundred healthy volunteers were recruited and randomized into 5 groups for 90 days. Group one added one normal egg to their daily diet and group two received a lutein enriched egg-yolk based beverage. Group three added one lutein enriched egg and group four one zeaxanthin enriched egg to their diet. Group five was the control group and individuals in this group did not modify their daily diet. Serum lutein and zeaxanthin concentrations and macular pigment densities were obtained at baseline, day 45 and day 90. Macular pigment density was measured by heterochromatic flicker photometry. Serum lutein concentration in the lutein enriched egg and egg yolk-based beverage groups increased significantly (p<0.001, 76% and 77%). A strong increase in the serum zeaxanthin concentration was observed in individuals receiving zeaxanthin enriched eggs (P< 0.001, 430%). No changes were observed in macular pigment density in the various groups tested. The results indicate that daily consumption of lutein or zeaxanthin enriched egg yolks as well as an egg yolk-based beverage show increases in serum lutein and zeaxanthin levels that are comparable with a daily use of 5 mg supplements. Trial Registration ClinicalTrials.gov NCT00527553 PMID:24675775

  10. Subspecies Identification and Significance of 257 Clinical Strains of Mycobacterium avium

    PubMed Central

    Tran, Quynh T.

    2014-01-01

    Mycobacterium avium is abundant in the environment. It has four subspecies of three types: the human or porcine type, M. avium subsp. hominissuis; the bird type, including M. avium subsp. avium serotype 1 and serotype 2, 3 (also M. avium subsp. silvaticum); and the ruminant type, M. avium subsp. paratuberculosis. We determined the subspecies of 257 M. avium strains isolated from patients at the M.D. Anderson Cancer Center from 2001 to 2010 and assessed their clinical significance. An assay of multiplex PCR was used for the typing. Results showed M. avium subsp. hominissuis to be most common (n = 238, 92.6%), followed by M. avium subsp. avium serotype 1 (n = 12, 4.7%) and serotype 2, 3 (n = 7, 2.7%). No strains of M. avium subsp. paratuberculosis were found. Of the 238 patients with M. avium subsp. hominissuis, 65 (27.3%) showed evidence of definite or probable infections, mostly in the respiratory tract, whereas the rest had weak evidence of infection. The bird-type subspecies, despite being infrequently isolated, caused relatively more definite and probable infections (10 of 19 strains, 52.6%). Overall, women of 50 years of age or older were more prone to M. avium infection than younger women or men of all ages were. We therefore conclude that M. avium subsp. hominissuis is the dominant M. avium subspecies clinically, that the two bird-type subspecies do cause human infections, and that M. avium infects mainly postmenopausal women. The lack of human clinical isolation of the ruminant type subspecies may need further investigation. PMID:24501026

  11. Clinically significant pharmacokinetic drug interactions of antiepileptic drugs with new antidepressants and new antipsychotics.

    PubMed

    Spina, Edoardo; Pisani, Francesco; de Leon, Jose

    2016-04-01

    Antiepileptic drugs (AEDs) are frequently co-prescribed with new antidepressants (ADs) or new antipsychotics (APs). A PubMed search with no time limit was used to update the review of the clinically significant pharmacokinetic (PK) drug interactions DIs (DIs) between AEDs with new ADs and APs. Our best interpretation of what to expect regarding dosing changes in the average patient after combining AEDs with new ADs or new APs is summarized on updated tables that integrate the information on in vitro metabolism studies, therapeutic drug monitoring (TDM) studies, case report/series and prospective studies. There will be a need to periodically update these dose correction factors as new knowledge becomes available. These tables will provide some orientation to clinicians with no TDM access and may also encourage clinicians to further study TDM. The clinical relevance of the inductive properties of carbamazepine, phenytoin, phenobarbital and primidone on new ADs and new APs and the inhibitory properties of valproic acid and some new ADs, are relatively well understood. On the other hand, PK DI studies combining new AEDs with weak inductive properties (particularly oxcarbazepine doses≥1200mg/day), topiramate doses≥400mg/day, clobazam, eslicarbazepine, and rufinamide), with new ADs and new APs are needed. Valproic acid may be 1) an inhibitor and/or inducer of clozapine and olanzapine with potential for clinically relevant DIs, 2) an inhibitor of paliperidone, and 3) a weak inducer of aripiprazole. Fluoxetine and fluvoxamine are relevant inhibitors of phenytoin and valproic acid and possibly of clobazam, lacosamide, phenobarbital, or primidone. PMID:26896788

  12. Clinical significance of late gadolinium enhancement in patients<20 years of age with hypertrophic cardiomyopathy.

    PubMed

    Smith, Brandon M; Dorfman, Adam L; Yu, Sunkyung; Russell, Mark W; Agarwal, Prachi P; Mahani, Maryam Ghadimi; Lu, Jimmy C

    2014-04-01

    Late gadolinium enhancement (LGE) on cardiovascular magnetic resonance imaging is associated with adverse events in adults with hypertrophic cardiomyopathy (HC). However, limited data exist on the extent and clinical significance of LGE in the pediatric population. In 30 patients (aged 14.1±3.2 years) with clinically diagnosed HC who underwent cardiovascular magnetic resonance imaging from 2007 to 2012, segments with hypertrophy and LGE were identified by 2 experienced readers blinded to outcome. Radial, circumferential, and longitudinal strains were evaluated using feature tracking software. The composite outcome was defined as cardiac death, nonsustained ventricular tachycardia, ventricular fibrillation, or appropriate implantable cardioverter-defibrillator discharge. LGE was present in 17 of 30 patients (57%), all in a midmyocardial pattern, with median 3 segments per patient (interquartile range [IQR] 2 to 5). No LGE was detected in patients without phenotypic hypertrophy. Segments with LGE had decreased radial (basal segments 20.7% vs 70.9%, p=0.01), circumferential (basal segments -23.2% vs -29.3%, p=0.04), and longitudinal strains (basal segments -13.8% vs -20.9%, p=0.04). After median follow-up of 26.9 months (IQR 7.5 to 34.3), 7 patients who had an adverse outcome (5 ventricular tachycardia, 1 appropriate implantable cardioverter-defibrillator discharge, and 1 death) had more segments of LGE (median 4, IQR 2 to 7 vs 0, IQR 0 to 2, p=0.01). One patient without LGE had ventricular tachycardia on exercise test. In conclusion, LGE occurs in a similar pattern in pediatric patients with HC as in adults, associated with hypertrophy, decreased myocardial strain, and adverse clinical outcomes. Further longitudinal studies are necessary to evaluate the rate of development of LGE and relation to outcomes in a larger cohort. PMID:24513464

  13. Routine Testing for Anaerobic Bacteria in Cerebrospinal Fluid Cultures Improves Recovery of Clinically Significant Pathogens

    PubMed Central

    Pittman, Meredith E.; Thomas, Benjamin S.; Wallace, Meghan A.; Weber, Carol J.

    2014-01-01

    In North America, the widespread use of vaccines targeting Haemophilus influenzae type b and Streptococcus pneumoniae have dramatically altered the epidemiology of bacterial meningitis, while the methodology for culturing cerebrospinal fluid (CSF) specimens has remained largely unchanged. The aims of this study were 2-fold: to document the current epidemiology of bacterial meningitis at a tertiary care medical center and to assess the clinical utility of routinely querying for anaerobes in CSF cultures. To that end, we assessed CSF cultures submitted over a 2-year period. A brucella blood agar (BBA) plate, incubated anaerobically for 5 days, was included in the culture procedure for all CSF specimens during the second year of evaluation. In the pre- and postimplementation years, 2,353 and 2,302 CSF specimens were cultured, with 49 and 99 patients having positive culture results, respectively. The clinical and laboratory data for patients with positive cultures were reviewed. Anaerobic bacteria were isolated in the CSF samples from 33 patients post-BBA compared to two patients pre-BBA (P = 0.01). The anaerobic isolates included Bacteroides thetaiotaomicron (n = 1), Propionibacterium species (n = 15), and Propionibacterium acnes (n = 19) isolates; all of these isolates were recovered on the BBA. Eight of the 35 patients from whom anaerobic organisms were isolated received antimicrobial therapy. Although six of these patients had central nervous system hardware, two patients did not have a history of a neurosurgical procedure and had community-acquired anaerobic bacterial meningitis. This study demonstrates that the simple addition of an anaerobically incubated BBA to the culture of CSF specimens enhances the recovery of clinically significant anaerobic pathogens. PMID:24622102

  14. Clinical significance of up-regulated ID1 expression in Chinese de novo acute myeloid leukemia

    PubMed Central

    Zhou, Jing-Dong; Yang, Lei; Zhu, Xiao-Wen; Wen, Xiang-Mei; Yang, Jing; Guo, Hong; Chen, Qin; Yao, Dong-Ming; Ma, Ji-Chun; Lin, Jiang; Qian, Jun

    2015-01-01

    To investigate the clinical significance of ID1 expression in Chinese de novo AML patients. Real-time quantitative PCR was carried out to detect the status of ID1 expression in 102 de novo AML patients and 28 controls. ID1 transcript level was significantly increased in AML compared to normal controls (p=0.029). The age in the patients with high ID1 expression is significantly older than in those with low ID1 expression (p=0.044). ID1 overexpression occurred with the highest frequency in the patients with poor karyotype (7/7, 100%), lower frequency in the patients with intermediate karyotype (28/60, 47%), and the lowest frequency in the patients with favorable karyotype (12/31, 39%). Both whole AML and non-M3 patients with high ID1 expression had significantly lower rate of complete remission than those with low ID1 expression (p=0.007 and 0.038). ID1 high-expressed patients showed significantly shorter overall survival (OS) than ID1 low-expressed patients in both whole AML and non-M3 according to Kaplan-Meier analysis (p=0.007 and 0.040). However, multivariate analysis indicated that ID1 overexpression was not an independent risk factor in both whole AML and non-M3 patients. However, the adverse impact of ID1 overexpression on outcome was revealed by both Kaplan-Meier analysis and multivariate analysis in the non-M3 patients less than 60 years old. Our study reveals that ID1 overexpression may be associated with higher risk karyotype classification and act as an independent risk factor in young non-M3 patients. PMID:26191235

  15. 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

  16. 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. PMID:26292645

  17. Factors influencing the magnitude and clinical significance of drug interactions between azole antifungals and select immunosuppressants.

    PubMed

    Saad, Aline H; DePestel, Daryl D; Carver, Peggy L

    2006-12-01

    The magnitude of drug interactions between azole antifungals and immunosuppressants is drug and patient specific and depends on the potency of the azole inhibitor involved, the resulting plasma concentrations of each drug, the drug formulation, and interpatient variability. Many factors contribute to variability in the magnitude and clinical significance of drug interactions between an immunosuppressant such as cyclosporine, tacrolimus, or sirolimus and an antifungal agent such as ketoconazole, fluconazole, itraconazole, voriconazole, or posaconazole. By bringing similarities and differences among these agents and their potential interactions to clinicians' attention, they can appreciate and apply these findings in a individualized patient approach rather than follow only the one-size-fits-all dosing recommendations suggested in many tertiary references. Differences in metabolism and in the inhibitory potency of cytochrome P450 3A4 and P-glycoprotein influence the onset, magnitude, and resolution of drug interactions and their potential effect on clinical outcomes. Important issues are the route of administration and the decision to preemptively adjust dosages versus intensive monitoring with subsequent dosage adjustments. We provide recommendations for the concomitant use of these agents, including suggestions regarding contraindicated combinations, those best avoided, and those requiring close monitoring of drug dosages and plasma concentrations. PMID:17125435

  18. Clinical significance and management of Barrett's esophagus with epithelial changes indefinite for dysplasia.

    PubMed

    Thota, Prashanthi N; Kistangari, Gaurav; Esnakula, Ashwini K; Gonzalo, David Hernandez; Liu, Xiu-Li

    2016-08-01

    Barrett's esophagus (BE) is defined as the extension of salmon-colored mucosa into the tubular esophagus ≥ 1 cm proximal to the gastroesophageal junction with biopsy confirmation of intestinal metaplasia. Patients with BE are at increased risk of esophageal adenocarcinoma (EAC), and undergo endoscopic surveillance biopsies to detect dysplasia or early EAC. Dysplasia in BE is classified as no dysplasia, indefinite for dysplasia (IND), low grade dysplasia (LGD) or high grade dysplasia (HGD). Biopsies are diagnosed as IND when the epithelial abnormalities are not sufficient to diagnose dysplasia or the nature of the epithelial abnormalities is uncertain due to inflammation or technical issues. Specific diagnostic criteria for IND are not well established and its clinical significance and management has not been well studied. Previous studies have focused on HGD in BE and led to changes and improvement in the management of BE with HGD and early EAC. Only recently, IND and LGD in BE have become focus of intense study. This review summarizes the definition, neoplastic risk and clinical management of BE IND. PMID:27602241

  19. 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. PMID:21032978

  20. What is the clinical significance of pulmonary hypertension in acute respiratory distress syndrome? A review

    PubMed Central

    Lai, Peggy S.; Mita, Carol; Thompson, B. Taylor

    2014-01-01

    Elevated pulmonary arterial pressures appear to be a prominent feature of the acute respiratory distress syndrome (ARDS). Current clinical guidelines for the management of ARDS do not specifically address treatment of pulmonary hypertension or associated right ventricular dysfunction because the clinical significance of this entity remains unclear. Interpretation of elevated pulmonary arterial pressures, pulmonary vascular resistance, and transpulmonary gradient as well as signs of right ventricular dysfunction is confounded by the effects of positive pressure ventilation. There does not appear to be a consistent relationship between the diagnosis of pulmonary hypertension or right ventricular failure and mortality in patients with ARDS, but it is unclear if right ventricular failure contributes to the mortality risk per se or if the underlying cause of pulmonary hypertension, including intravascular micro and macro thrombosis, are simply markers for systemic dysregulation of coagulation and fibrinolysis that may lead to multiorgan failure in ARDS. While studies of pulmonary vasodilator therapies have not shown a mortality benefit in ARDS, such trials have targeted improved oxygenation rather than improved pulmonary hemodynamics so that the possible contribution of improved right ventricular function to better outcomes has not been directly tested in large trials. Future studies are needed to determine if treatment of pulmonary hypertension and associated right ventricular dysfunction will affect mortality in patients with ARDS. PMID:24193181

  1. Clinical significance and management of Barrett’s esophagus with epithelial changes indefinite for dysplasia

    PubMed Central

    Thota, Prashanthi N; Kistangari, Gaurav; Esnakula, Ashwini K; Gonzalo, David Hernandez; Liu, Xiu-Li

    2016-01-01

    Barrett’s esophagus (BE) is defined as the extension of salmon-colored mucosa into the tubular esophagus ≥ 1 cm proximal to the gastroesophageal junction with biopsy confirmation of intestinal metaplasia. Patients with BE are at increased risk of esophageal adenocarcinoma (EAC), and undergo endoscopic surveillance biopsies to detect dysplasia or early EAC. Dysplasia in BE is classified as no dysplasia, indefinite for dysplasia (IND), low grade dysplasia (LGD) or high grade dysplasia (HGD). Biopsies are diagnosed as IND when the epithelial abnormalities are not sufficient to diagnose dysplasia or the nature of the epithelial abnormalities is uncertain due to inflammation or technical issues. Specific diagnostic criteria for IND are not well established and its clinical significance and management has not been well studied. Previous studies have focused on HGD in BE and led to changes and improvement in the management of BE with HGD and early EAC. Only recently, IND and LGD in BE have become focus of intense study. This review summarizes the definition, neoplastic risk and clinical management of BE IND. PMID:27602241

  2. 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.

  3. 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

  4. Ultrasonography-Based Thyroidal and Perithyroidal Anatomy and Its Clinical Significance.

    PubMed

    Ha, Eun Ju; Baek, Jung Hwan; Lee, Jeong Hyun

    2015-01-01

    Ultrasonography (US)-guided procedures such as ethanol ablation, radiofrequency ablation, laser ablation, selective nerve block, and core needle biopsy have been widely applied in the diagnosis and management of thyroid and neck lesions. For a safe and effective US-guided procedure, knowledge of neck anatomy, particularly that of the nerves, vessels, and other critical structures, is essential. However, most previous reports evaluated neck anatomy based on cadavers, computed tomography, or magnetic resonance imaging rather than US. Therefore, the aim of this article was to elucidate US-based thyroidal and perithyroidal anatomy, as well as its clinical significance in the use of prevention techniques for complications during the US-guided procedures. Knowledge of these areas may be helpful for maximizing the efficacy and minimizing the complications of US-guided procedures for the thyroid and other neck lesions. PMID:26175574

  5. A Mutation-Sensitive Switch Assay to Detect Five Clinically Significant Epidermal Growth Factor Receptor Mutations

    PubMed Central

    Liu, Bin; Zhou, Lin; Wang, Qian

    2015-01-01

    Epidermal growth factor receptor (EGFR) mutations can affect the therapeutic efficacy of drugs used to treat nonsmall-cell lung cancer (NSCLC). We aimed to develop methods to detect five common EGFR somatic mutations in tumor tissues from NSCLC patients by using a nanoscale mutation-sensitive switch consisting of a high-fidelity polymerase and phosphorothioate-modified allele-specific primers. The five clinically significant EGFR mutations examined here are S768I, T790M, L858R, and 15- and 18-bp deletion mutations in exon 19. Our assays showed sensitivities of 100 copies and specificities of more than three log scales for matched templates relative to mismatched templates by routine polymerase chain reaction (PCR), real-time PCR, and multiplex PCR. This assay would be superior to DNA sequencing in situations where mutant DNA is not abundant. PMID:25918867

  6. Clinical significance of elevated serum and urine amylase levels in patients with appendicitis.

    PubMed

    Swensson, E E; Maull, K I

    1981-12-01

    During the 45 month period beginning January 1977, 251 patients with a pathologically confirmed diagnosis of acute appendicitis underwent celiotomy at the Medical College of Virginia Hospital. A preoperative serum or urine amylase determination was recorded in 155 of the patients (62 percent). Of this group, 15 patients (10 percent) had elevation of serum amylase or 2 hour urine amylase. Hyperamylasemia or hyperamylasuria directly led to misdiagnosis or treatment delay in 5 of the 15 patients. Appendiceal rupture occurred in three patients, two of whom had prolonged (greater than 1 month) hospitalizations directly attributable to the misdiagnosis. As a result of this study, we conclude that (1) acute appendicitis and elevated amylase levels may occur concurrently, (2) hyperamylasemia or hyperamylasuria should not dissuade the surgeon from early operation if other clinical features suggest appendicitis, and (3) abdominal pain and elevation of amylase level define significant intraabdominal disease, not specifically pancreatic disease. PMID:6172043

  7. Ultrasonography-Based Thyroidal and Perithyroidal Anatomy and Its Clinical Significance

    PubMed Central

    Ha, Eun Ju; Lee, Jeong Hyun

    2015-01-01

    Ultrasonography (US)-guided procedures such as ethanol ablation, radiofrequency ablation, laser ablation, selective nerve block, and core needle biopsy have been widely applied in the diagnosis and management of thyroid and neck lesions. For a safe and effective US-guided procedure, knowledge of neck anatomy, particularly that of the nerves, vessels, and other critical structures, is essential. However, most previous reports evaluated neck anatomy based on cadavers, computed tomography, or magnetic resonance imaging rather than US. Therefore, the aim of this article was to elucidate US-based thyroidal and perithyroidal anatomy, as well as its clinical significance in the use of prevention techniques for complications during the US-guided procedures. Knowledge of these areas may be helpful for maximizing the efficacy and minimizing the complications of US-guided procedures for the thyroid and other neck lesions. PMID:26175574

  8. Quantitative analysis of macular contraction in idiopathic epiretinal membrane

    PubMed Central

    2014-01-01

    Background We aimed to quantify the displacement of macular capillaries using infrared fundus photographs and image processing software (ImageJ) in patients with idiopathic epiretinal membrane (ERM) who have undergone vitrectomy and to analyze the correlation between vessel displacement and retinal thickness. Methods This prospective study included 16 patients who underwent vitrectomy for idiopathic ERM. Ophthalmic examination and optical coherence tomography (OCT) were performed before and 3 months after surgery. The length of radial vessel segment included in each area (VLA) and the length from the foveola to the vessel branching point (FBL) depending on the superior, inferior, nasal, and temporal areas of the macula were measured using infrared fundus images and image processing software (ImageJ). Preoperative and postoperative parameters were compared and correlations between VLA, FBL, macular thickness, and visual acuity were assessed. Results The VLA of superior, inferior, and temporal areas showed a significant postoperative reduction. VLA differences showed a positive correlation with differences in macular thickness, which corresponded to the superior, inferior, and temporal areas; however, no correlation was observed in the nasal area. The FBL of the superior and inferior areas was significantly increased postoperatively. A positive correlation was observed between FBL differences and macular thickness differences in the superior area. Postoperative change in VLA and FBL did not show a significant correlation with postoperative best corrected visual acuity (BCVA) and BCVA differences. Conclusions Infrared fundus photographs and image processing software can be useful for quantifying progressive changes in retinal surface distortion after surgical removal of ERM. Macular edema and vascular distortion showed significant improvement after surgery. Furthermore, a correlation was observed between topographic and tomographic changes. PMID:24735324

  9. 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

  10. Clinical significance of serum claudin-1 and claudin-7 levels in patients with colorectal cancer

    PubMed Central

    KARABULUT, MEHMET; ALIS, HALIL; BAS, KORAY; KARABULUT, SENEM; AFSAR, CIGDEM USUL; OGUZ, HILAL; GUNALDI, MERAL; AKARSU, CEVHER; KONES, OSMAN; AYKAN, NURI FARUK

    2015-01-01

    The present study aimed to investigate the serum levels and clinical relevance of claudin (CLDN) 1 and CLDN7 in patients with colorectal cancer (CRC). A total of 140 patients with a pathologically confirmed diagnosis of CRC were enrolled in this study. The serum levels of CLDN1 and CLDN7 were determined using the solid-phase sandwich ELISA method. A total of 40 healthy age- and gender-matched controls were included in the analysis. The median age of the patients was 60 years (range, 24–84 years). The localization of the tumor in the majority of the patients was the colon (n=81, 58%). Of the 55 metastatic patients who received palliative chemotheraphy, 31% were chemotherapy-responsive. The baseline median serum CLDN1 and CLDN7 levels were significantly lower in non-metastatic and metastatic patients compared with those in healthy controls (CLND1, P=0.008 and 0.002; and CLND7, P=0.002 and 0.002, respectively). Moreover, known clinical variables, including poor performance status and high carcinoembryonic antigen (CEA) levels were found to be associated with lower serum CLDN1 concentrations for all patients (P=0.03 and P=0.03, respectively). High T stage and high CEA levels were found to be correlated with lower serum CLDN7 concentrations for all patients (P=0.04 and 0.03, respectively). A correlation was identified between CLDN1 and CLDN7 levels in non-metastatic and metastatic CRC patients (both P-values <0.001). Our study results did not reveal any statistical significance for serum CLDN1 or CLND7 concentrations regarding progression-free and overall survival rate. Therefore, reduced serum levels of CLDN1 and CLND7 may be useful markers in the differential diagnosis of CRC. PMID:26807230

  11. 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

  12. 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

  13. Clinical significance of accurate identification of lymph node status in distant metastatic gastric cancer

    PubMed Central

    Zhang, Jingwen; Wang, Hongqiang; Su, Yuqi; Huang, Na; Shi, Min; Bin, Jianping; Liao, Yulin; Liao, Wangjun

    2016-01-01

    PURPOSE The clinical consequences of accurately identifying lymph node (LN) status in distant metastatic gastric cancer (DMGC) are unclear. We aimed to determine the prognostic significance of N stage, positive LN (PLN) count, and the positive LN ratio (LNR). We also retrospectively compared survival outcomes of DMGC patients stratified by LN dissection (LND). RESULTS LND was performed in 1593 patients. The CSS was significantly different between groups divided according to N stage, PLN, and LNR in DMGC patients who underwent LND. Lower LNR was an independent predictor of longer survival in all kinds of patients cohorts, whereas PLN was not such a predictor. PLN count correlated with LND number and LNR. No correlation existed between LNR and LND number. Undergoing LND and having a higher number of dissected LNs were associated with superior CSS. MATERIALS AND METHODS Data from 1889 DMGC patients treated between 2004 and 2009, and documented in the Surveillance, Epidemiology, and End Results (SEER) registry, were reviewed. Pearson's correlation coefficient and the Chi-square test were used to study the relationships between LND number, PLN count, N stage, and the LNR. Cancer-specific survival (CSS) was evaluated using Kaplan-Meier analysis, with the log-rank test performed for univariate analysis (UVA) and the Cox proportional hazards model employed for multivariate analysis (MVA). CONCLUSION LN metastatic variables play important roles in the prognostic evaluation and treatment decisions of DMGC patients. Accurate identification of LN status in DMGC patients is critical. LND performance is associated with increased survival and has clinical practicability. PMID:26556854

  14. Biological and clinical significance of PARP1 protein expression in breast cancer.

    PubMed

    Green, Andrew R; Caracappa, Daniela; Benhasouna, Ahmed A; Alshareeda, Alaa; Nolan, Christopher C; Macmillan, R Douglas; Madhusudan, Srinivasan; Ellis, Ian O; Rakha, Emad A

    2015-01-01

    Poly(ADP-ribose) polymerase-1 (PARP1) is a key facilitator of DNA repair. PARP inhibitors have gained recent attention as promising therapeutic agents for the treatment of solid tumours including breast cancer (BC). However, the biological and clinical significance of PARP1 expression in BC and its role in DNA-damage response (DDR) remain to be defined. We investigated the expression of PARP1 expression, cleaved (PARP1c) and non-cleaved (PAR1nc) forms, in a large and well-characterised cohort of clinically annotated stage I-III operable BCs (n = 1,269) and 43 BRCA1-mutated BCs using immunohistochemistry. PARP1 expression was correlated to clinicopathological variables, outcome and expression of other key DNA repair proteins (BRCA1, RAD51, Ku70/80, PIASγ and CHK1). Expression of PARP1 was exclusively nuclear. 49 and 85 % of sporadic BC showed expression PARP1nc and PARP1c, respectively. In BRCA1-mutated tumours, PARP1nc/PARP1c was highly expressed (95 and 79 %, respectively). PARP1nc expression was positively associated with premenopausal younger age patients, larger size and higher tumour grade. PARP1 was positively associated with DDR-proteins; RAD51, BRCA1, CHK1 and PIASγ (p < 0.001). Negative association was found between PARP1nc and Ki67. PARP1c was associated with ER (p < 0.001). Different associations between PARP1 and DDR-proteins were observed when stratified based on ER/BRCA1 status. PARP1 was not an independent predictor of outcome in sporadic or BRCA1-mutated BC. Our results demonstrate a potential biological role for PARP1c and PARP1nc in DNA repair in BC based on the significant association with other key DNA damage repair proteins. These associations were not restricted to ER-negative or triple-negative subgroup. PMID:25528020

  15. AB029. The clinical significance of RigiScan plus detection

    PubMed Central

    Gao, Bing; Mu, Hongtao; Zhang, Zhichao; Yuan, Yiming; Peng, Jing; Xin, Zhongcheng; Guo, Yinglu

    2016-01-01

    Erectile dysfunction (ED) is a common disease in male outpatient service, the penis hardness testing of ED in the clinical diagnosis has important significance, past some detection methods, such as nocturnal penile tumescence monitoring (NPT) due to time-consuming is not easy in outpatient service and a vasodilator agent intervention tests such as color Doppler detection due to the injection of drugs in the penis is difficult for patients to accept. In 1965 night rapid eye movement sleep phase 3–5 times of penile erection phenomenon was first reported by Fisher, in 1970 the night monitoring instrument of penis erectile hardness is used for evaluation of male erectile function. In 1985 researchers reported the RigiScan plus software was used to record of nocturnal erection, 1994 this method was gradually improved and used in clinical application by Levine. Sol reported that after taking sildenafil the patient was given audio-visual stimulation to induce the penis erects, then the RigiScan plus was used to record erection hardness in 2006. Due to the complexity of the etiology of ED, for the evaluation of penile erectile function should also be in many ways any single check has its limitations, the drug combined with audio-visual sense stimulation induced penile erection hardness monitoring (AVSS + RigiScan plus) in newly diagnosed patients with erectile function has a certain significance. Compared with AVSS + RigiScan examination, NPT is more expensive, time-consuming, and cumbersome, and patients feel unwell. And AVSS + RigiScan is simple, effective, easy, cheap, and the diagnostic accuracy rate matching to NPT, it is suitable for routine examination of patients with newly diagnosed ED.

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

    PubMed

    Pechan, Peter; Wadsworth, Samuel; Scaria, Abraham

    2015-07-01

    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. PMID:25524721

  17. 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. PMID:11045244

  18. 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

  19. The significance of the determination of lymphocytes with clinical manifestation of ophthalmic zoster sine herpete

    PubMed Central

    Marumoto, Tatsuya; Hiratsuka, Yoshimune; Murakami, Akira

    2010-01-01

    Objective: To examine the significance of VZV-IgG (IgG) enzyme immunoassay (EIA) and the determination of peripheral blood lymphocyte counts in the diagnosis of ophthalmic zoster sine herpete (ophthalmic ZSH). Method: Clinical case-control study with a sample of 65 patients with ophthalmic ZSH (16 males and 49 females; mean age 56 ± 18 years) in whom pressure elicited pain in tender points of Valleix (tender points of sites at which the trigeminal nerve appears subcutaneously). A total of 41 healthy controls (17 males and 24 females, mean age 48 ± 21 years) were also recruited. In each group, IgG and lymphocyte count were determined upon receiving the consent of patients. Multiple logistic regression analysis was used to evaluate the factors associated with diagnosis of ophthalmic ZSH. Odds ratios and 95% confidence intervals (CI) were determined for each variable. Results: Lymphocyte count in the patients with ophthalmic ZSH was significantly low, though there were no significant differences in age, gender, and IgG between the two groups. Multiple logistic regression analysis revealed that lymphocytes pose a significant prognostic factor, and in case of 1,800 lymphocytes/μl or more, the odds ratio to less than1,800 lymphocytes/μl was 0.29 (95% CI: 0.12–0.72). Conclusion: Patients with orbital pain should be suspected as having ophthalmic ZSH as this allows for the determination of lymphocyte counts after tender points were confirmed. The swift diagnosis of ophthalmic ZSH and the administration of antiviral drugs from an early stage improve the subjective symptoms of the patient and is regarded as necessary to reduce the risk of severe complications. PMID:20689799

  20. Clinical Significance of Positive Pelvic Washings in Uterine Papillary Serous Carcinoma Confined to an Endometrial Polyp.

    PubMed

    Hanley, Krisztina Z; Fadare, Oluwole; Fisher, Kevin E; Atkins, Kristen A; Mosunjac, Marina B

    2016-05-01

    Uterine papillary serous carcinoma (UPSC) represents 10% of endometrial carcinomas. Significant number of patients initially present with extrauterine disease. The role of adjuvant treatment in low stage, especially polyp-confined UPSC is controversial. This multi-institutional study evaluated the significance of positive pelvic washing (PW) and adjuvant treatment on disease recurrence in a setting of endometrial polyp-confined UPSC. Surgical pathology files from 3 institutions were searched for cases of endometrial polyp-confined UPSC. Following histologic review, cases were clinically staged as Stage I, without myoinvasion or lymphovascular invasion. Clinicopathologic characteristics, results of PW, and type of adjuvant therapy were recorded. Statistical analysis using the Kaplan-Meier method for survival and Fisher exact test were performed. Thirty-three patients were included in the study. All patients were diagnosed with polyp-confined UPSC. The size of the polyp ranged from 0.3 to 4.3 cm. PW was positive for tumor cells in 8/33 (24%) patients. Twenty-two patients (66.6%) received some type of adjuvant treatment. Six patients (18%) developed recurrent disease. There was no significant difference in disease-free survival in the patients receiving adjuvant treatment versus not (P=0.375). However, there was significant association (P=0.0013) between positive PW and disease recurrence. Data are conflicting whether positive PW affects prognosis in low-stage endometrial carcinomas. Our study showed that in UPSC, malignant cells can be present in PW without lymphovascular invasion or myoinvasion and may have negative prognostic implication. Our data also reflect the controversies in the role of adjuvant treatment in endometrium-confined UPSC. PMID:26535985

  1. Polycystic ovary syndrome: aggressive or protective factor for the retina? Evaluation of macular thickness and retinal nerve fiber layers using high-definition optical coherence tomography.

    PubMed

    de Souza-Júnior, José Edvan; Garcia, Carlos Alexandre de Amorim; Soares, Elvira Maria Mafaldo; Maranhão, Técia Maria Oliveira; Lemos, Telma Maria Araújo Moura; Azevedo, George Dantas

    2015-01-01

    Objective. To compare macular thickness (MT) and retinal nerve fiber layers (RNFL) between women with polycystic ovary syndrome (PCOS) and healthy women. Materials and Methods. The study included 45 women with PCOS and 47 ovulatory women undergoing clinical-gynecological and ophthalmic evaluations, including measurement of MT, RNFL, and optic disc parameters using optical coherence tomography. Results. The superior RNFL around the optic nerve was significantly thicker in PCOS than in healthy volunteers (P = 0.036). After stratification according to insulin resistance, the temporal inner macula (TIM), the inferior inner macula (IIM), the nasal inner macula (NIM), and the nasal outer macula (NOM) were significantly thicker in PCOS group than in control group (P < 0.05). Both the presence of obesity associated with insulin resistance (P = 0.037) and glucose intolerance (P = 0.001) were associated with significant increase in the PC1 mean score, relative to MT. A significant increase in the PC2 mean score occurred when considering the presence of metabolic syndrome (P < 0.0001). There was a significant interaction between obesity and inflammation in a decreasing mean PC2 score relative to macular RNFL thickness (P = 0.034). Conclusion. Decreased macular RNFL thickness and increased total MT are associated with metabolic abnormalities, while increased RNFL thickness around the optic nerve is associated with hormonal changes inherent in PCOS. PMID:25763280

  2. Interventions for the treatment of uveitic macular edema: a systematic review and meta-analysis

    PubMed Central

    Karim, Rushmia; Sykakis, Evripidis; Lightman, Susan; Fraser-Bell, Samantha

    2013-01-01

    Background Uveitic macular edema is the major cause of reduced vision in eyes with uveitis. Objectives To assess the effectiveness of interventions in the treatment of uveitic macular edema. Search strategy Cochrane Central Register of Controlled Trials, Medline, and Embase. There were no language or data restrictions in the search for trials. The databases were last searched on December 1, 2011. Reference lists of included trials were searched. Archives of Ophthalmology, Ophthalmology, Retina, the British Journal of Ophthalmology, and the New England Journal of Medicine were searched for clinical trials and reviews. Selection criteria Participants of any age and sex with any type of uveitic macular edema were included. Early, chronic, refractory, or secondary uveitic macular edema were included. We included trials that compared any interventions of any dose and duration, including comparison with another treatment, sham treatment, or no treatment. Data collection and analysis Best-corrected visual acuity and central macular thickness were the primary outcome measures. Secondary outcome data including adverse effects were collected. Conclusion More results from randomized controlled trials with long follow-up periods are needed for interventions for uveitic macular edema to assist in determining the overall long-term benefit of different treatments. The only intervention with sufficiently robust randomized controlled trials for a meta-analysis was acetazolamide, which was shown to be ineffective in improving vision in eyes with uveitic macular edema, and is clinically now rarely used. Interventions showing promise in this disease include dexamethasone implants, immunomodulatory drugs and anti-vascular endothelial growth-factor agents. When macular edema has become refractory after multiple interventions, pars plana vitrectomy could be considered. The disease pathophysiology is uncertain and the course of disease unpredictable. As there are no clear guidelines from

  3. Expression of O6-methylguanine DNA methyltransferase (MGMT) and its clinical significance in gastroenteropancreatic neuroendocrine neoplasm

    PubMed Central

    Yang, Qiu-Chen; Wang, Yu-Hong; Lin, Yuan; Xue, Ling; Chen, Yuan-Jia; Chen, Min-Hu; Chen, Jie

    2014-01-01

    O6-methylguanine-DNA methyltransferase (MGMT) is a widespread DNA repair enzyme defending against mutation caused by guanine O6-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 (χ2 = 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. PMID:25120800

  4. The clinical significance of the neutrophil-to-lymphocyte ratio in multiple sclerosis.

    PubMed

    Demirci, Seden; Demirci, Serpil; Kutluhan, Suleyman; Koyuncuoglu, Hasan Rifat; Yurekli, Vedat Ali

    2016-08-01

    Multiple sclerosis (MS) is one of the main chronic inflammatory diseases of the central nervous system that causes functional disability in young people. The aim of this study was to investigate the neutrophil-to-lymphocyte ratio (NLR) in patients with MS and the relationship between the NLR and the severity of the disease. One hundred and two MS patients (31 patients were in relapse; 71 patients were in remission) and 56 healthy controls were included. Complete blood counts as well as demographic and clinical data from MS patients were evaluated retrospectively. The NLRs were calculated for all participants and were compared; the cut-off value was also determined for the NLR and Expanded Disability Status Scale (EDSS). MS patients had a significantly higher NLR (p < 0.001) than the control group. The NLR levels were significantly higher in patients who were in relapse than patients in remission (p = 0.039). The cut-off value for the NLR to predict an MS diagnosis and activity were determined to be 2.04 and 3.90, respectively. The NLRs were directly correlated with erythrocyte sedimentation rate levels (r = 0.795, p < 0.001). Logistic regression analysis with dichotomous EDSS score showed that a high NLR was an independent predictor of the progression of disability. The NLR may be a biomarker that has simple, quick, inexpensive and reproducible properties in MS to predict patient's prognosis. PMID:26000934

  5. Potential clinical significance of ERβ ON promoter methylation in sporadic breast cancer.

    PubMed

    Božović, Ana; Markićević, Milan; Dimitrijević, Bogomir; Jovanović Ćupić, Snežana; Krajnović, Milena; Lukić, Silvana; Mandušić, Vesna

    2013-01-01

    The aim of the study was to assess how hypermethylation of the ON promoter of the estrogen receptor beta (ERβ) gene affects its expression (at the mRNA and protein level) and to correlate these with some clinical and histopathological parameters. A total of 131 samples of frozen breast cancer tissue was analyzed. A custom-designed, two-step PCR method was used to measure the methylation index of the ERβ gene ON promoter region. Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed to quantify mRNA of the ERβ1 isoform, while ERβ1 protein was determined using the Western blot method. There was a significant difference in the methylation index of the ERβ gene ON promoter between the groups of patients with negative and positive axillary lymph node status (P = 0.03). In addition, the methylation index of the ON promoter was positively correlated with estrogen receptor alfa (ERα) protein levels (ρ = 0.31, P = 0.02). There was a significant difference in the methylation index of the ON promoter between the progesterone receptor (PR)-negative and PR-positive groups of patients (P = 0.01). ERβ1 protein levels were negatively correlated with ERα protein (ρ = -0.27, P < 0.01). The methylation index of the ON promoter could be a more reliable additional parameter for prediction and/or prognosis in breast cancer than ERβ1-mRNA and/or protein levels. PMID:23794253

  6. Relationship between ultrasound elastography and myofibroblast distribution in breast cancer and its clinical significance.

    PubMed

    Hao, Yi; Guo, Xia; Ma, Binlin; Zhu, Lin; Liu, Lisha

    2016-01-01

    The study investigated the relationship between ultrasound elastography (USE) scoring and myofibroblast distribution with expression features of α-SMA +/CD34- in patients of Uyghur and Han ethnicities with breast masses in Xinjiang, China. The data was used to evaluate its clinical significance in the early diagnosis of breast cancer. A total of 300 patients with breast masses were included in the study, which involved conventional sonography and USE, with histopathologic diagnosis as the reference standard. Myofibroblast distribution was investigated by detecting the expression levels of α-SMA and CD34 in lesions using immunohistochemistry and real-time PCR. Out of 300 lesions, 185 were histologically malignant and 115 benign. The mean elasticity score for malignant lesions was significantly higher than for benign lesions. The expression level of α-SMA was elevated while the expression level of CD34 was lower in malignancies, compared with benign lesions. The expression of α-SMA was positively associated with the USE scores, while a negative relationship was observed between CD34 expression and USE scoring. The combination of USE and molecular diagnosis provides a promising modality for the early diagnosis and evaluation of the risks in particular types of breast cancer. PMID:26846996

  7. Biological and clinical significance of epigenetic silencing of MARVELD1 gene in lung cancer

    PubMed Central

    Shi, Ming; Wang, Shan; Yao, Yuanfei; Li, Yiqun; Zhang, Hao; Han, Fang; Nie, Huan; Su, Jie; Wang, Zeyu; Yue, Lei; Cao, Jingyan; Li, Yu

    2014-01-01

    Epigenetic silence in cancer frequently altered signal-transduction pathways during the early stages of tumor development. Recent progress in the field of cancer epigenetics has led to new opportunities for diagnosis and treatment of cancer. We previously demonstrated that novel identified nuclear factor MARVELD1 was widely expressed in human tissues, but down-regulated by promoter methylation in multiple cancers. This study was carried out to determine the biological and clinical significance of MARVELD1 gene silencing in lung cancer. Here, we found the reduced MARVELD1 expression significantly correlated with diagnostic histopathology and malignant degree of lung cancers. DNA hypermethylation and histone deacetylation synergistically inactivated MARVELD1 gene in lung cancer cells. Moreover, MARVELD1 modulated the efficiency of nonsense-mediated mRNA decay (NMD) through interaction with NMD core factor SMG1. The decreased MARVELD1 level in lung cancer reduces NMD efficiency through diminishing the association between NMD complex component UPF1/SMG1 and premature termination codons containing mRNA (PTC-mRNA). The results suggested that MARVELD1 silencing is an appealing diagnostic biomarker for lung cancer and epigenetic silencing of MARVELD1 gene links with the regulatory mechanism of NMD pathway in lung cancer, which may be required for tumorigenesis. PMID:25520033

  8. Relationship between ultrasound elastography and myofibroblast distribution in breast cancer and its clinical significance

    PubMed Central

    Hao, Yi; Guo, Xia; Ma, Binlin; Zhu, Lin; Liu, Lisha

    2016-01-01

    The study investigated the relationship between ultrasound elastography (USE) scoring and myofibroblast distribution with expression features of α-SMA + /CD34− in patients of Uyghur and Han ethnicities with breast masses in Xinjiang, China. The data was used to evaluate its clinical significance in the early diagnosis of breast cancer. A total of 300 patients with breast masses were included in the study, which involved conventional sonography and USE, with histopathologic diagnosis as the reference standard. Myofibroblast distribution was investigated by detecting the expression levels of α-SMA and CD34 in lesions using immunohistochemistry and real-time PCR. Out of 300 lesions, 185 were histologically malignant and 115 benign. The mean elasticity score for malignant lesions was significantly higher than for benign lesions. The expression level of α-SMA was elevated while the expression level of CD34 was lower in malignancies, compared with benign lesions. The expression of α-SMA was positively associated with the USE scores, while a negative relationship was observed between CD34 expression and USE scoring. The combination of USE and molecular diagnosis provides a promising modality for the early diagnosis and evaluation of the risks in particular types of breast cancer. PMID:26846996

  9. Immunohistochemical Expression and Clinical Significance of Suggested Stem Cell Markers in Hepatocellular Carcinoma

    PubMed Central

    Sung, Jong Jin; Noh, Sang Jae; Bae, Jun Sang; Park, Ho Sung; Jang, Kyu Yun; Chung, Myoung Ja; Moon, Woo Sung

    2016-01-01

    Background: Increasing evidence has shown that tumor initiation and growth are nourished by a small subpopulation of cancer stem cells (CSCs) within the tumor mass. CSCs are posited to be responsible for tumor maintenance, growth, distant metastasis, and relapse after curative operation. We examined the expression of CSC markers in paraffin-embedded tissue sections of hepatocellular carcinoma (HCC) and correlated the results with clinicopathologic characteristics. Methods: Immunohistochemical staining for the markers believed to be expressed in the CSCs, including epithelial cell adhesion molecule (EpCAM), keratin 19 (K19), CD133, and CD56, was performed in 82 HCC specimens. Results: EpCAM expression was observed in 56% of the HCCs (46/82) and K19 in 6% (5/82). EpCAM expression in HCC significantly correlated with elevated α-fetoprotein level, microvessel invasion of tumor cells, and high histologic grade. In addition, EpCAM expression significantly correlated with K19 expression. The overall survival and relapsefree survival rates in patients with EpCAM-expressing HCC were relatively lower than those in patients with EpCAM-negative HCC. All but two of the 82 HCCs were negative for CD133 and CD56, respectively. Conclusions: Our results suggest that HCCs expressing EpCAM are associated with unfavorable prognostic factors and have a more aggressive clinical course than those not expressing EpCAM. Further, the expression of either CD133 or CD56 in paraffin-embedded HCC tissues appears to be rare. PMID:26581206

  10. Clinical significance of topoisomerase 2A expression and gene change in operable invasive breast cancer.

    PubMed

    Qiao, Jiang-Hua; Jiao, De-Chuang; Lu, Zhen-Duo; Yang, Sen; Liu, Zhen-Zhen

    2015-09-01

    This study aims to investigate clinical significance of topoisomerase 2A (TOP2A) expression and TOP2A gene change in operable invasive breast cancer. This is a retrospective analysis, which includes 256 patients diagnosed as operable invasive breast cancer. All postoperational waxed specimens were subjected to resectioning for staining. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), KI-67, TOP2A expression, and TOP2A gene changes were detected by immunohistochemistry (IHC) and fluorescent in situ hybridization technique (FISH), respectively. Correlation between TOP2A expression and clinicopathological characteristics was also investigated. Effects of TOP2A protein or gene changes on survival rate were detected. Results indicated that 165 were TOP2A positive (64.5 %), and 31 were gene amplification positive (12.1 %). Positive rate of TOP2A expression showed significant correlations with ER, KI-67, and HER-2. The difference of 5-year overall survival (OS) between TOP2A-positive and TOP2A-negative groups did not reach statistical significance (OS: P = 0.321, 85.9 vs. 79.6 %; disease-free survival [DFS]: P = 0.247, 83.3 vs. 75.3 %). Five-year OS in TOP2A amplification group was 68.8 %, which is lower than deficiency and control group (P > 0.05). Subgroup analysis showed no significant differences of OS and DFS either between TOP2A-positive and TOP2A-negative groups or between TOP2A amplification and control group in population of patients with HER-2 amplification, triple negative breast cancer, or hormone-positive breast cancer. In conclusion, positive rate of TOP2A expression correlates significantly with ER, KI-67, and HER-2. However, prognostic significance of either TOP2A expression or TOP2A gene changes in breast cancer and its various subtypes is limited. PMID:25846735

  11. 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

  12. Polymorphism of human cytochrome P450 2D6 and its clinical significance: part II.

    PubMed

    Zhou, Shu-Feng

    2009-01-01

    Part I of this article discussed the potential functional importance of genetic mutations and alleles of the human cytochrome P450 2D6 (CYP2D6) gene. The impact of CYP2D6 polymorphisms on the clearance of and response to a series of cardiovascular drugs was addressed. Since CYP2D6 plays a major role in the metabolism of a large number of other drugs, Part II of the article highlights the impact of CYP2D6 polymorphisms on the response to other groups of clinically used drugs. Although clinical studies have observed a gene-dose effect for some tricyclic antidepressants, it is difficult to establish clear relationships of their pharmacokinetics and pharmacodynamic parameters to genetic variations of CYP2D6; therefore, dosage adjustment based on the CYP2D6 phenotype cannot be recommended at present. There is initial evidence for a gene-dose effect on commonly used selective serotonin reuptake inhibitors (SSRIs), but data on the effect of the CYP2D6 genotype/phenotype on the response to SSRIs and their adverse effects are scanty. Therefore, recommendations for dose adjustment of prescribed SSRIs based on the CYP2D6 genotype/phenotype may be premature. A number of clinical studies have indicated that there are significant relationships between the CYP2D6 genotype and steady-state concentrations of perphenazine, zuclopenthixol, risperidone and haloperidol. However, findings on the relationships between the CYP2D6 genotype and parkinsonism or tardive dyskinesia treatment with traditional antipsychotics are conflicting, probably because of small sample size, inclusion of antipsychotics with variable CYP2D6 metabolism, and co-medication. CYP2D6 phenotyping and genotyping appear to be useful in predicting steady-state concentrations of some classical antipsychotic drugs, but their usefulness in predicting clinical effects must be explored. Therapeutic drug monitoring has been strongly recommended for many antipsychotics, including haloperidol, chlorpromazine, fluphenazine

  13. Clinical significance of glycoprotein nonmetastatic B and its association with HER2 in breast cancer

    PubMed Central

    Kanematsu, Masako; Futamura, Manabu; Takata, Masafumi; Gaowa, Siqin; Yamada, Atsuko; Morimitsu, Kasumi; Morikawa, Akemi; Mori, Ryutaro; Hara, Hideaki; Yoshida, Kazuhiro

    2015-01-01

    Glycoprotein nonmetastatic B (GPNMB) is a potential oncogene that is particularly expressed in melanoma and breast cancer (BC). To clarify its clinical significance in BC, we measured serum GPNMB in vivo and investigated its cross talk with human epidermal growth factor 2 (HER2). GPNMB was expressed in four of six breast cell lines (SK-BR-3, BT-474, MDA-MD-231, and MDA-MD-157), two of six colorectal cell lines, and two of four gastric cancer (GC) cell lines. We established a GPNMB quantification system using enzyme-linked immunosorbent assay (ELISA) for these cell lines. We measured serum GPNMB in vivo in 162 consecutive BC patients and in 88 controls (50 colorectal cancer [CC] and 38 GC patients). The GPNMB concentration in BC, CC and GC was 8.163, 5.751 and 6.55 ng/mL, respectively. The GPNMB level was significantly higher in BC patients than in CC patients (P = 0.021). The HER2-rich subtype of BC patients had significantly higher GPNMB levels than other subtypes (vs. Luminal; P = 0.038; vs. DCIS; P = 0.0195). These high GPNMB levels decreased after treatment (surgery/chemotherapy). Next, we examined the relationship between GPNMB and HER2 in vitro using SK-BR3 and BT-474 (HER2-positive/GPNMB-positive) cells. GPNMB depletion by small interfering RNA (siRNA) increased both HER2 expression and phosphorylation. Trastuzumab (Tra) in combination with docetaxel promoted cell growth inhibition, and treatment with Tra or an Extracellular signal-related kinase (ERK) inhibitor enhanced GPNMB expression. These results indicate that GPNMB might be a surrogate marker for BC and may cross talk with the HER2 signal pathway. GPNMB may therefore emerge as an important player in anti-HER2 therapy. PMID:26077887

  14. The clinical significance of forkhead box protein A1 and its role in colorectal cancer

    PubMed Central

    Ma, Wenqi; Jiang, Jue; Li, Miao; Wang, Hua; Zhang, Hongli; He, Xin; Huang, Lili; Zhou, Qi

    2016-01-01

    Forkhead box protein A1 (FOXA1) is a transcription factor; recent studies have reported that FOXA1 has an oncogenic or tumor suppressive role in human malignancies, and its expression is associated with the prognosis of patients with cancer. However, further studies are required to determine the clinical significance of FOXA1 and its role in colorectal cancer (CRC). In the present study, FOXA1 expression was detected in 90 samples of CRC tissues and matched noncancerous tissues using immunohistochemistry. In these cases, FOXA1 expression was detected in 57.8% (52/90) of the CRC samples, whereas only 37.8% (34/90) of the noncancerous specimens exhibited a positive FOXA1 signal. In addition, the present study demonstrated that the mRNA expression levels of FOXA1 were significantly increased in CRC tissues compared with in matched tumor-adjacent tissues. Furthermore, the positive expression of FOXA1 was associated with poor clinicopathological characteristics of CRC, including poor tumor differentiation, large tumor size, lymph node metastases and advanced tumor-node-metastasis tumor stage. Notably, patients with CRC with positive FOXA1 expression exhibited a significantly reduced 5-year survival rate compared with those with negative FOXA1 expression. Multivariate Cox regression analysis revealed that FOXA1 expression was an independent prognostic indicator for patients with CRC. In addition, FOXA1 knockdown evidently inhibited cell proliferation and induced apoptosis in SW480 and HCT116 CRC cells. Notably, FOXA1 knockdown also prominently reduced the expression of yes-associated protein (YAP) in SW480 and HCT116 cells. In conclusion, the results of the present study indicated that FOXA1 may be considered a potential prognostic marker, and may promote tumor growth of CRC by upregulating YAP expression. PMID:27484093

  15. Clinical and epidemiological significance of enterococci intrinsically resistant to vancomycin (possessing the vanC genotype)

    PubMed Central

    Toye, B; Shymanski, J; Bobrowska, M; Woods, W; Ramotar, K

    1997-01-01

    Constitutive low-level vancomycin resistance is found intrinsically in certain enterococcal species and is encoded by vanC ligase genes. These intrinsically vancomycin-resistant enterococci (VRE) will be referred to as VANC VRE. A prospective study to determine the clinical and epidemiologic significance of VANC VRE was conducted. VANC VRE were recovered from the stools of 34 of 601 (5.7%) patients, a rate similar to that obtained for the stools of 100 outpatients in the community (5%). VANC VRE were also isolated from the nonstool specimens of 9 of 538 patients (1.7%), including two patients with bacteremia. No VRE of the vanA or vanB genotypes were detected in nonstool specimens. Eighty-two hospital contacts of the first 23 patients found to be colonized or infected with VANC VRE were screened, and 6 contacts were found to be gastrointestinal carriers of VANC VRE. However, typing of isolates from these 6 contacts by pulsed-field gel electrophoresis with SmaI showed the isolates to be unique and different from those recovered from the index patients. In fact, all VANC VRE isolates from different patients in this study were unique. A case-control study with patients who were negative when screened for VANC VRE as controls failed to identify any risk factor associated with colonization or infection with this organism. VANC VRE were infrequently recovered from clinical specimens but were occasionally found as part of the normal stool flora. Since no transmission between patients was documented, additional isolation procedures may not be necessary for patients colonized or infected with VANC VRE. PMID:9399514

  16. 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

  17. 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

  18. Incidence Rates of Clinically Significant Tinnitus: 10-Year Trend From a Cohort Study in England

    PubMed Central

    Wallenhorst, Christopher; McFerran, Don; Hall, Deborah A.

    2015-01-01

    Objective: To investigate the incidence of tinnitus that burdens the health service in England. Design: This was an observational study of 4.7 million residents of England under 85 years of age who were at risk for developing clinically significant tinnitus (sigT). SigT was defined by a discharge from hospital with a primary diagnosis of tinnitus, or a primary care recording of tinnitus with subsequent related medical follow-up within 28 days. The database used was the Clinical Practice Research Datalink and individual records were linked to additional data from the Hospital Episode Statistics. The observational period was from January 1, 2002 to December 31, 2011. Age-, gender-, and calendar year-specific incidence rates for and cumulative incidences of sigT were estimated and a projection of new cases of sigT between 2012 and 2021 was performed. Results: There were 14,303 incident cases of sigT identified among 26.5 million person-years of observation. The incidence rate was 5.4 new cases of sigT per 10,000 person-years (95% confidence interval: 5.3 to 5.5). The incidence rate did not depend on gender but increased with age, peaking at 11.4 per 10,000 in the age group 60 to 69 years. The annual incidence rate of sigT increased from 4.5 per 10,000 person-years in 2002 to 6.6 per 10,000 person-years in 2011. The 10-year cumulative incidence of sigT was 58.4 cases (95% confidence interval: 57.4 to 59.4) per 10,000 residents. Nearly 324,000 new cases of sigT are expected to occur in England between 2012 and 2021. Conclusions: Tinnitus presents a burden to the health care system that has been rising in recent years. Population-based studies provide crucial underpinning evidence; highlighting the need for further research to address issues around effective diagnosis and clinical management of this heterogeneous condition. PMID:25470370

  19. Trends in Clinically Significant Pain Prevalence Among Hospitalized Cancer Patients at an Academic Hospital in Taiwan

    PubMed Central

    Wang, Wei-Yun; Ho, Shung-Tai; Wu, Shang-Liang; Chu, Chi-Ming; Sung, Chun-Sung; Wang, Kwua-Yun; Liang, Chun-Yu

    2016-01-01

    Abstract Clinically significant pain (CSP) is one of the most common complaints among cancer patients during repeated hospitalizations, and the prevalence ranges from 24% to 86%. This study aimed to characterize the trends in CSP among cancer patients and examine the differences in the prevalence of CSP across repeated hospitalizations. A hospital-based, retrospective cohort study was conducted at an academic hospital. Patient-reported pain intensity was assessed and recorded in a nursing information system. We examined the differences in the prevalence of worst pain intensity (WPI) and last evaluated pain intensity (LPI) of ≥4 or ≥7 points among cancer inpatients from the 1st to the 18th hospitalization. Linear mixed models were used to determine the significant difference in the WPI and LPI (≥4 or ≥7 points) at each hospitalization. We examined 88,133 pain scores from the 1st to the 18th hospitalization among cancer patients. The prevalence of the 4 CSP types showed a trend toward a reduction from the 1st to the 18th hospitalization. There was a robust reduction in the CSP prevalence from the 1st to the 5th hospitalization, except in the case of LPI ≥ 7 points. The prevalence of a WPI ≥ 4 points was significantly higher (0.240-fold increase) during the 1st hospitalization than during the 5th hospitalization. For the 2nd, 3rd, and 4th hospitalizations, there was a significantly higher prevalence of a WPI ≥ 4 points compared with the 5th hospitalization. We also observed significant reductions in the prevalence of a WPI ≥ 7 points during the 1st to the 4th hospitalizations, an LPI ≥ 4 points during the 1st to the 3rd hospitalizations, and an LPI ≥ 7 points during the 1st to the 2nd hospitalization. Although the prevalence of the 4 CSP types decreased gradually, it is impossible to state the causative factors on the basis of this observational and descriptive study. The next step will examine the factors that determine the CSP prevalence among

  20. Correlating MDCT Liver Injury Grade and Clinical Outcome in Patients Without Significant Extra-hepatic Injury.

    PubMed

    Kumar, Ravi; Kumar, Atin; Baliyan, Vinit; Gamanagatti, Shivanand; Bhalla, Ashu Seith; Sharma, Raju; Gupta, Amit; Kumar, Subodh; Misra, M C

    2016-08-01

    The aim of the study was to correlate multi-detector computed tomography (MDCT) grading with clinical severity and outcome in liver trauma patients without significant extrahepatic injury. Over a period of 2 years (2011-2013), all patients showing evidence of liver injury on contrast-enhanced CT (CECT) abdomen and without significant extrahepatic trauma were prospectively included in the study. Correlation between the CT injury grade and outcome in terms of mortality, duration of ICU/hospital stay, fluid and blood requirements, need for intervention and complications were assessed. The significance of the difference in mortality, duration of ICU/hospital stay, fluid requirement and blood requirements among the patients with various injury grades was assessed by Kruskal-Wallis test. The significance of the difference in need for intervention and complications among the patients with various injury grades was assessed by Fisher's exact test. A total of 198 patients were found to have evidence of hepatic injury on CECT. Out of 198 patients, 117 had insignificant extrahepatic trauma. The overall mean age for these 117 patients was 25.74 ± 15.53 (age range 2-84 years). Death rates according to AAST grades were 0 % in grades II and III, 6.89 % in grade IV and 9.09 % in grade V (p = 0.053). The mean ICU and total hospital stay for grade II was 1.32 and 5.91 days, for grade III was 1.76 and 8.48, for grade IV was 2.86 and 10.31 days and for grade V was 6.54 and 12 days, respectively (p = 0.0001 for ICU, p = 0.0003 for total stay). Mean input and fluid deficit according to various grades were 8634/2607 ml for grade II, 9535/2555 ml for grade III, 15,549/6242 ml for grade IV and 19,958/8280 ml for grade V (p value input-0.0016, output-input (fluid deficit)-0.0001). Average unit of RBC and sum of the blood products transfused were 1.73 and 2.26 for grade II, 2.18 and 2.72 for grade III, 3.03 and 6.27 for grade IV, 6.85 and 38.12 for grade V

  1. Cystoid Macular Edema in Bietti's Crystalline Retinopathy

    PubMed Central

    2014-01-01

    A 27-year-old man with progressive bilateral visual decline was diagnosed to have Bietti's crystalline dystrophy (BCD). Fluorescein angiography revealed bilateral petaloid type late hyperfluorescence implicating concurrent cystoid macular edema (CME). Optical coherence tomography exhibited cystoid foveal lacunas OU. During the follow-up of six years, intraretinal crystals reduced in amount but CME persisted angiographically and tomographically. CME is among the rare macular features of BCD including subfoveal sensorial detachment, subretinal neovascular membrane, and macular hole. PMID:24949209

  2. Short-term safety and efficacy of intravitreal 0.7-mg dexamethasone implants for pseudophakic cystoid macular edema

    PubMed Central

    Al Zamil, Waseem M.

    2014-01-01

    Aims To determine the feasibility, safety, and clinical efficacy of intravitreal 0.7-mg dexamethasone implants (Ozurdex) in patients with refractory cystoid macular edema after uncomplicated cataract surgery. Methods and materials In this study, 11 eyes of 11 patients affected by pseudophakic cystoid macular edema refractory to medical treatment were treated with a single intravitreal injection of a dexamethasone implant. Follow-up visits involved Early Treatment Diabetic Retinopathy Study visual acuity testing, optical coherence tomography imaging, and ophthalmoscopic examination. Results The follow-up period was six months. The mean duration of cystoid macular edema before treatment with Ozurdex was 7.7 months (range, 6–10 months). The baseline mean best corrected visual acuity (BCVA) was 0.58 ± 0.17 logarithm of the minimum angle of resolution (logMAR). The mean BCVA improved to 0.37 ± 0.16 logMAR (p = 0.008) and 0.20 ± 0.13 logMAR (p = 0.001) after 1 and 3 months, respectively. At the last follow-up visit (6-month follow-up), the mean BCVA was 0.21 ± 0.15 logMAR (p = 0.002). The mean foveal thickness at baseline (513.8 μm, range, 319–720 μm) decreased significantly (308.0 μm; range, 263–423 μm) by the end of the follow-up period (p < 0.0001). Final foveal thickness was significantly correlated with baseline BCVA (r = 0.57, p = 0.002). No ocular or systemic adverse events were observed. Conclusions Short-term results suggest that the intravitreal dexamethasone implant is safe and well tolerated in patients with pseudophakic cystoid macular edema. Treated eyes had revealed a significant improvement in BCVA and decrease in macular thickness by optical coherence tomography. PMID:25892932

  3. Clinical significance of bax/bcl-2 ratio in chronic lymphocytic leukemia.

    PubMed

    Del Principe, Maria Ilaria; Dal Bo, Michele; Bittolo, Tamara; Buccisano, Francesco; Rossi, Francesca Maria; Zucchetto, Antonella; Rossi, Davide; Bomben, Riccardo; Maurillo, Luca; Cefalo, Mariagiovanna; De Santis, Giovanna; Venditti, Adriano; Gaidano, Gianluca; Amadori, Sergio; de Fabritiis, Paolo; Gattei, Valter; Del Poeta, Giovanni

    2016-01-01

    In chronic lymphocytic leukemia the balance between the pro-apoptotic and anti-apoptotic members of the bcl-2 family is involved in the pathogenesis, chemorefractoriness and clinical outcome. Moreover, the recently proposed anti-bcl-2 molecules, such as ABT-199, have emphasized the potential role of of bcl-2 family proteins in the context of target therapies. We investigated bax/bcl-2 ratio by flow cytometry in 502 patients and identified a cut off of 1.50 to correlate bax/bcl-2 ratio with well-established clinical and biological prognosticators. Bax/bcl-2 was 1.50 or over in 263 patients (52%) with chronic lymphocytic leukemia. Higher bax/bcl-2 was associated with low Rai stage, lymphocyte doubling time over 12 months, beta-2 microglobulin less than 2.2 mg/dL, soluble CD23 less than 70 U/mL and a low risk cytogenetic profile (P<0.0001). On the other hand, lower bax/bcl-2 was correlated with unmutated IGHV (P<0.0001), mutated NOTCH1 (P<0.0001) and mutated TP53 (P=0.00007). Significant shorter progression-free survival and overall survival were observed in patients with lower bax/bcl-2 (P<0.0001). Moreover, within IGHV unmutated (168 patients) and TP53 mutated (37 patients) subgroups, higher bax/bcl-2 identified cases with significant longer PFS (P=0.00002 and P=0.039). In multivariate analysis of progression-free survival and overall survival, bax/bcl-2 was an independent prognostic factor (P=0.0002 and P=0.002). In conclusion, we defined the prognostic power of bax/bcl-2 ratio, as determined by a flow cytometric approach, and highlighted a correlation with chemoresistance and outcome in chronic lymphocytic leukemia. Finally, the recently proposed new therapies employing bcl-2 inhibitors prompted the potential use of bax/bcl-2 ratio to identify patients putatively resistant to these molecules. PMID:26565002

  4. Clinical significance of bax/bcl-2 ratio in chronic lymphocytic leukemia

    PubMed Central

    Del Principe, Maria Ilaria; Bo, Michele Dal; Bittolo, Tamara; Buccisano, Francesco; Rossi, Francesca Maria; Zucchetto, Antonella; Rossi, Davide; Bomben, Riccardo; Maurillo, Luca; Cefalo, Mariagiovanna; De Santis, Giovanna; Venditti, Adriano; Gaidano, Gianluca; Amadori, Sergio; de Fabritiis, Paolo; Gattei, Valter; Del Poeta, Giovanni

    2016-01-01

    In chronic lymphocytic leukemia the balance between the pro-apoptotic and anti-apoptotic members of the bcl-2 family is involved in the pathogenesis, chemorefractoriness and clinical outcome. Moreover, the recently proposed anti-bcl-2 molecules, such as ABT-199, have emphasized the potential role of of bcl-2 family proteins in the context of target therapies. We investigated bax/bcl-2 ratio by flow cytometry in 502 patients and identified a cut off of 1.50 to correlate bax/bcl-2 ratio with well-established clinical and biological prognosticators. Bax/bcl-2 was 1.50 or over in 263 patients (52%) with chronic lymphocytic leukemia. Higher bax/bcl-2 was associated with low Rai stage, lymphocyte doubling time over 12 months, beta-2 microglobulin less than 2.2 mg/dL, soluble CD23 less than 70 U/mL and a low risk cytogenetic profile (P<0.0001). On the other hand, lower bax/bcl-2 was correlated with unmutated IGHV (P<0.0001), mutated NOTCH1 (P<0.0001) and mutated TP53 (P=0.00007). Significant shorter progression-free survival and overall survival were observed in patients with lower bax/bcl-2 (P<0.0001). Moreover, within IGHV unmutated (168 patients) and TP53 mutated (37 patients) subgroups, higher bax/bcl-2 identified cases with significant longer PFS (P=0.00002 and P=0.039). In multivariate analysis of progression-free survival and overall survival, bax/bcl-2 was an independent prognostic factor (P=0.0002 and P=0.002). In conclusion, we defined the prognostic power of bax/bcl-2 ratio, as determined by a flow cytometric approach, and highlighted a correlation with chemoresistance and outcome in chronic lymphocytic leukemia. Finally, the recently proposed new therapies employing bcl-2 inhibitors prompted the potential use of bax/bcl-2 ratio to identify patients putatively resistant to these molecules. PMID:26565002

  5. Clinical Significance and Epidemiologic Analyses of Mycobacterium avium and Mycobacterium intracellulare among Patients without AIDS

    PubMed Central

    Han, Xiang Y.; Tarrand, Jeffrey J.; Infante, Rosa; Jacobson, Kalen L.; Truong, Mylene

    2005-01-01

    The clinical significance and prevalence of Mycobacterium avium and Mycobacterium intracellulare were analyzed in a cohort of 7,472 patients who, from 1999 to 2003, sought care at the University of Texas M.D. Anderson Cancer Center, Houston, and had cultures performed for mycobacteria. Patients were stratified for age, sex, and underlying diseases, and bacteria were identified by 16S rRNA gene sequencing. M. avium was isolated in 62 (0.83%) of 7,472 patients and M. intracellulare in 65 (0.87%). Clinically, only 10 of the 62 (16.2%) patients with M. avium had probable to definite evidence of infection, whereas the majority (83.8%) had weak evidence of infection. Sex and age did not affect the isolation or infection of M. avium. Hematological tumors predisposed to M. avium colonization but not infection. In contrast, 41 of the 65 (63.1%) patients with M. intracellulare had probable to definite infection, a level much higher than those with M. avium (P < 0.001). M. intracellulare was more prevalent in women (1.33% of 3,311) than in men (0.50% of 4,161) (P < 0.001), and underlying diseases had no effect in women. Men with lung cancer had a higher prevalence (1.37%) than men without (0.34%) (4.0-fold; P < 0.001), but it was similar to that in women. A marked age trend for the isolation of M. intracellulare among women was noted: 0.27% (1-fold) for ages of <50 years, 0.85% (3.1-fold) for ages 50 to 59 years, 1.50% (5.6-fold) for ages 60 to 69 years, and 3.74% (13.9-fold) for ages ≥70 years (trend, P < 0.001). The combined rate for women ≥50 was 1.86% (95% confidence interval [1.30 to 2.42%]) (6.9-fold). Together, these results suggest that, among non-AIDS patients, M. intracellulare is more pathogenic and tends to infect women increasingly beyond menopause (age ≥50 years) regardless of underlying disease. The prevalence rate of 1.86% in postmenopausal women suggests the need to further investigate the public health significance of M. intracellulare. PMID:16145084

  6. 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

  7. Pachychoroid neovasculopathy and age-related macular degeneration

    PubMed Central

    Miyake, Masahiro; Ooto, Sotaro; Yamashiro, Kenji; Takahashi, Ayako; Yoshikawa, Munemitsu; Akagi-Kurashige, Yumiko; Ueda-Arakawa, Naoko; Oishi, Akio; Nakanishi, Hideo; Tamura, Hiroshi; Tsujikawa, Akitaka; Yoshimura, Nagahisa

    2015-01-01

    Pachychoroid neovasculopathy is a recently proposed clinical entity of choroidal neovascularization (CNV). As it often masquerades as neovascular age-related macular degeneration (AMD), it is currently controversial whether pachychoroid neovasculopathy should be distinguished from neovascular AMD. This is because its characteristics have yet to be well described. To estimate the relative prevalence of pachychoroid neovasculopathy in comparison with neovascular AMD and to investigate the phenotypic/genetic differences of the two diseases, we evaluated 200 consecutive Japanese patients who agreed to participate in the genetic study and diagnosed with pachychoroid neovasculopathy or neovascular AMD. Pachychoroid neovasculopathy was observed in 39 individuals (19.5%), which corresponds to one fourth of neovascular AMD. Patients with pachychoroid neovasculopathy were significantly younger (p = 5.1 × 10−5) and showed a greater subfoveal choroidal thickness (p = 3.4 × 10−14). Their genetic susceptibility to AMD was significantly lower than that of neovascular AMD; ARMS2 rs10490924 (p = 0.029), CFH rs800292 (p = 0.013) and genetic risk score calculated from 11 AMD susceptibility genes (p = 3.8 × 10−3). Current results implicate that the etiologies of the two conditions must be different. Thus, it will be necessary to distinguish these two conditions in future studies. PMID:26542071

  8. Clinically Significant Depressive Symptoms as a Risk Factor for HIV Infection Among Black MSM in Massachusetts

    PubMed Central

    Reisner, Sari L.; Skeer, Margie; Bright, Donna; Cranston, Kevin; Isenberg, Deborah; Bland, Sean; Barker, Thomas A.; Mayer, Kenneth H.

    2013-01-01

    High rates of depression have been observed among men who have sex with men (MSM) relative to the general adult male population; however, a dearth of research has explored depression among Black MSM. Black MSM (n = 197) recruited via modified respondent-driven sampling between January and July 2008 completed an interviewer-administered quantitative assessment and voluntary HIV counseling and testing. Bivariate and multivariable logistic regression procedures examined the associations of demographics, behavioral HIV risk factors, and psychosocial variables with depressive symptoms by severity, using the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Adjusting for demographic and behavioral variables, significant factors associated with (1) clinically significant depressive symptoms (33%; CES-D score ≥ 16): being publicly insured by Medicaid, having serodiscordant anal sex with a casual male partner, and being diagnosed with an STD in the prior 12 months; (2) moderate depressive symptoms (19%; CES-D score 16–26): having serodiscordant unprotected anal sex with a casual male partner and being diagnosed with an STD in the prior 12 months; (3) severe depressive symptoms (14%; CES-D score 27+): being publicly insured by Medicaid and reporting difficulty accessing healthcare in the past 12 months. Moderately depressed Black MSM may be more likely to engage in behaviors that place them at increased risk for HIV and other STDs. HIV prevention interventions for Black MSM may benefit from incorporating screening and/or treatment for depression, allowing MSM who are depressed to respond more effectively to behavioral change approaches. PMID:19462228

  9. Clinical significance of subepithelial growth patterns in non-muscle invasive bladder cancer

    PubMed Central

    2011-01-01

    Background We evaluated the clinical significance and prognostic value of histopathological features of bladder cancer, such as subepithelial growth patterns and tumor growth pattern at the invasion front. Methods In total, 130 patients newly diagnosed with non-muscle invasive bladder cancer and underwent transurethral resection between 1998 and 2009 were enrolled. Subepithelial growth patterns consisting of endophytic growth pattern (EGP) and von Brunn's nest involvement (VBNI) were investigated using hematoxylin and eosin-stained slides, and their frequency of occurrence, prognostic value, and correlation with other clinicopathological features was evaluated. Results EGP and VBNI were found in 40 (30.8%) and 5 (3.9%) of the 130 cases, respectively. Of the 26 pT1 tumors, the growth pattern at the invasion front was trabecular in 17 (65.4%) and infiltrative in 9 (34.6%). Although 8 (47.1%) of 17 trabecular tumors coexisted with EGP, no cases with infiltrative tumors had EGP (p = 0.023). VBNI correlated with high tumor grades (p = 0.006) and lymphovascular involvement (p = 0.026). The multivariate Cox proportional hazards analysis revealed that tumor diameter less than 3 cm (p = 0.04) and intravesical bacillus Calmette-Guérin therapy (p = 0.004) were independent favorable prognostic factors for recurrence-free survival, whereas tumor stage was an independent poor prognostic factor for disease progression (p = 0.006). Conclusions Subepithelial growth patterns were not a significant prognostic factor in this study. Additionally, no tumors with an infiltrative growth pattern coexisted with EGP, suggesting that determining the presence of EGP might be helpful for managing non-muscle invasive bladder cancers. PMID:21816111

  10. PCDH8 is Frequently Inactivated by Promoter Hypermethylation in Liver Cancer: Diagnostic and Clinical Significance

    PubMed Central

    Zhang, Cheng; Peng, Yunfei; Yang, Fan; Qin, Ruixi; Liu, Wenjun; Zhang, Cuijuan

    2016-01-01

    AIM: Protocadherin-8 (PCDH8) plays an important role in signaling pathways of cell adhesin, proliferation, and migration. It has been reported that PCDH8 is mutated or methylated in several human cancers. However, little is known about PCDH8 in liver cancer. The aim of this study was to investigate the protein expression and promoter methylation status of PCDH8 in liver cancer and evaluate the association between PCDH8 methylation and the clinicopathological features. METHODS: The methylation status of PCDH8 in 42 hepatocellular carcinoma (HCC), 8 Cholangiocarcinoma (CC) and 50 normal liver tissues were examined using methylation-specific PCR (MSP) and the protein expression of PCDH8 was detected by immunohistochemistry. The relationships between PCDH8 methylation and clinicopathological features as well as overall survival of patients were evaluated. RESULTS: The PCDH8 methylation was more frequent in liver cancer tissues than that in the normal liver tissues (88% vs. 32%, P < 0.001), and is significantly associated with loss of its protein expression (P = 0.004). Moreover, there is a significant correlation between PCDH8 methylation and the alpha-fetoprotein (AFP) level (P = 0.008). Kaplan-Meier survival analysis revealed that patients with PCDH8 methylation have shorter OS and PFS than those without PCDH8 methylation (P = 0.041 and P = 0.028, respectively). CONCLUSION: PCDH8 is often inactivated by promoter methylation in liver cancer. PCDH8 methylation can serve as a valuable diagnostic biomarker for early detection of liver cancer and might be useful to predict an unfavorable clinical feature. PMID:26918058

  11. Assigning site of origin in metastatic neuroendocrine neoplasms: a clinically significant application of diagnostic immunohistochemistry.

    PubMed

    Bellizzi, Andrew M

    2013-09-01

    The neuroendocrine epithelial neoplasms (NENs) include well-differentiated neuroendocrine tumors (WDNETs) and poorly differentiated neuroendocrine carcinomas (PDNECs). Whereas PDNECs are highly lethal, with localized Merkel cell carcinoma somewhat of an exception, WDNETs exhibit a range of "indolent" biologic potentials-from benign to widely metastatic and eventually fatal. Within each of these 2 groups there is substantial morphologic overlap. In the metastatic setting, the site of origin of a WDNET has significant prognostic and therapeutic implications. In the skin, Merkel cell carcinoma must be distinguished from spread of a visceral PDNEC. This review intends to prove the thesis that determining the site of origin of a NEN is clinically vital and that diagnostic immunohistochemistry is well suited to the task. It will begin by reviewing current World Health Organization terminology for the NENs, as well as an embryologic and histologic pattern-based classification. It will present population-based data on the relative frequency and biology of WDNETs arising at various anatomic sites, including the frequency of metastases of unknown primary, and comment on limitations of contemporary imaging techniques, as a means of defining the scope of the problem. It will go on to discuss the therapeutic significance of site of origin. The heart of this review is a synthesis of data compiled from >100 manuscripts on the expression of individual markers in WDNETs and PDNECs, as regards site of origin. These include proteins that are considered "key markers" and others that are either useful "secondary markers," potentially very useful markers that need to be further vetted, or ones that are widely applied despite a lack of efficacy. It will conclude with my approach to the metastatic NEN of unknown origin. PMID:23939147

  12. 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

  13. 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

  14. Chemokine receptor CXCR4 and its ligand CXCL12 expressions and clinical significance in bladder cancer.

    PubMed

    Yang, D L; Xin, M M; Wang, J S; Xu, H Y; Huo, Q; Tang, Z R; Wang, H F

    2015-01-01

    It is well known that chemokine receptors and their ligands play important roles in mediating the invasion and metastasis of malignant tumors. This aim of this study was to investigate the expression and clinical significance of chemokine receptor CXCR4 and its ligand CXCL12 in bladder tumor tissues. Cancerous and adjacent normal bladder tissues were collected from 42 patients. The expressions of CXCR4 and CXCL12 proteins were then detected by immunohistochemistry, and the expressions of CXCR4 and CXCL12 mRNAs were detected by RT-PCR. Bladder cancer tissues showed higher positive expressions of CXCR4 and CXCL12 than those in normal bladder mucosal tissues (z = 7.332, 6.758, P < 0.001). Positive expressions of CXCR4 and CXCL12 were related to the differentiation degree and invasive depth of cancer tissues (z = 2.598-4.594, P < 0.05), but not to patient gender or age (z = 0.273-0.554, P > 0.05). The expression of CXCR4 was positively correlated to CXCL12 expression in bladder cancer tissues (r = 0.661, P < 0.05). RT-PCR revealed that CXCR4 and CXCL12 mRNAs were not expressed in normal tissues. Moreover, with increased depth of invasion, CXCR4 and CXCL12 mRNA expressions gradually increased in bladder cancer tissues and showed significant intergroup differences (F = 56.642, 67.928, P < 0.01). Taken together, these results indicate that the chemokine receptor CXCR4 and its ligand CXCL12 play important roles in the occurrence and development of bladder cancer. PMID:26782415

  15. Clinical significance, antimicrobial susceptibility and molecular identification of Nocardia species isolated from children with cystic fibrosis.

    PubMed

    Betrán, Ana; Villuendas, M Cruz; Rezusta, Antonio; Pereira, Javier; Revillo, M José; Rodríguez-Nava, Verónica

    2016-01-01

    Nocardia is an opportunistic pathogen that causes respiratory infections in immunocompromised patients. The aim of this study was to analyze the epidemiology, clinical significance and antimicrobial susceptibility of Nocardia species isolated from eight children with cystic fibrosis. The isolated species were identified as Nocardia farcinica, Nocardia transvalensis, Nocardia pneumoniae, Nocardia veterana and Nocardia wallacei. N. farcinica was isolated in three patients and all of them presented lung affectation with a chronic colonization and pneumonia. N. farcinica showed resistance against gentamicin, tobramycin, cefotaxime, but was susceptible to trimethoprim-sulfamethoxazole and amikacin. N. transvalensis, which was isolated from two patients, showed an association with chronic colonization. N. transvalensis was resistant to tobramycin and amikacin, but susceptible to ciprofloxacin, trimethoprim-sulfamethoxazole and cefotaxime. N. veterana, N. pneumoniae and N. wallacei were isolated from three different patients and appeared in transitory lung colonization. N. veterana and N. pneumoniae were susceptible to imipenem, trimethoprim-sulfamethoxazole, amikacin, tobramycin, and cefotaxime. N. wallacei was resistant to amikacin, tobramycin, imipenem, and trimethoprim-sulfamethoxazole and susceptible to ciprofloxacin and cefotaxime. All the isolates were identified up to species level by 16S rRNA gene sequencing. The presence of Nocardia in the sputum of patients with cystic fibrosis is not always an indication of an active infection; therefore, the need for a treatment should be evaluated on an individual basis. The detection of multidrug-resistant species needs molecular identification and susceptibility testing, and should be performed for all Nocardia infections. PMID:27155949

  16. The biological significance and clinical applications of exosomes in ovarian cancer.

    PubMed

    Dorayappan, Kalpana Deepa Priya; Wallbillich, John J; Cohn, David E; Selvendiran, Karuppaiyah

    2016-07-01

    Exosomes are nano-sized (20-100nm) vesicles released by a variety of cells and are generated within the endosomal system or at the plasma membrane. There is emerging evidence that exosomes play a key role in intercellular communication in ovarian and other cancers. The protein and microRNA content of exosomes has been implicated in various intracellular processes that mediate oncogenesis, tumor spread, and drug resistance. Exosomes may prime distant tissue sites for reception of future metastases and their release can be mediated by the tumor microenvironment (e.g., hypoxia). Ovarian cancer-derived exosomes have unique features that could be leveraged for use as biomarkers to facilitate improved detection and treatment of the disease. Further, exosomes have the potential to serve as targets and/or drug delivery vehicles in the treatment of ovarian cancer. In this review we discuss the biological and clinical significance of exosomes relevant to the progression, detection, and treatment of ovarian cancer. PMID:27058839

  17. 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. PMID:26356330

  18. Clinical significance of automatic warning function of cardiac remote monitoring systems in preventing acute cardiac episodes

    PubMed Central

    Chen, Shou-Qiang; Xing, Shan-Shan; Gao, Hai-Qing

    2014-01-01

    Objective: In addition to ambulatory Holter electrocardiographic recording and transtelephonic electrocardiographic monitoring (TTM), a cardiac remote monitoring system can provide an automatic warning function through the general packet radio service (GPRS) network, enabling earlier diagnosis, treatment and improved outcome of cardiac diseases. The purpose of this study was to estimate its clinical significance in preventing acute cardiac episodes. Methods: Using 2 leads (V1 and V5 leads) and the automatic warning mode, 7160 patients were tested with a cardiac remote monitoring system from October 2004 to September 2007. If malignant arrhythmias or obvious ST-T changes appeared in the electrocardiogram records was automatically transferred to the monitoring center, the patient and his family members were informed, and the corresponding precautionary or therapeutic measures were implemented immediately. Results: In our study, 274 cases of malignant arrhythmia, including sinus standstill and ventricular tachycardia, and 43 cases of obvious ST-segment elevation were detected and treated. Because of early detection, there was no death or deformity. Conclusions: A cardiac remote monitoring system providing an automatic warning function can play an important role in preventing acute cardiac episodes. PMID:25674124

  19. Clinical significance of regulatory B cells in the peripheral blood of patients with oesophageal cancer

    PubMed Central

    Qian, Li; Bian, Guang-Rong; Wang, Yan; Hu, Juan; Liu, Xia; Xu, Yan

    2015-01-01

    B cell subsets have been found to exhibit a negative regulatory function, like Tregs. The present study investigates the effects of CD5+CD19+ interleukin (IL)-10 (B10) on the occurrence and development of oesophageal carcinoma by analysing B10 levels in the peripheral blood of patients with oesophageal carcinoma. Peripheral blood of 120 oesophageal cancer patients and 120 healthy controls were collected, and regulatory B cell counts were determined by flow cytometry. The level of B10 cells in the peripheral blood of patients with oesophageal carcinoma was significantly higher than that in healthy controls (p < 0.05). In addition, B10 levels in stage III-IV patients (3.5 ±0.7%) were higher than those in stage I-II patients (2.5 ±0.6%), which were in turn higher than those in the healthy controls (1.3 ±0.3%). The level of B10 increased with clinical progression of oesophageal cancer, suggesting that B10 cells may influence the development or progression of oesophageal cancer. PMID:26557042

  20. Clinical significance of preoperative thrombocytosis in patients who underwent radical nephrectomy for nonmetastatic renal cell carcinoma

    PubMed Central

    Choi, Jae Young; Ko, Young Hwii

    2016-01-01

    Purpose The aim of this study was to examine the association of preoperative thrombocytosis with the prognosis of patients with nonmetastatic renal cell carcinoma (RCC). Materials and Methods We conducted a retrospective analysis of 187 patients who underwent a radical nephrectomy for nonmetastatic RCC between July 1997 and June 2009. Thrombocytosis was defined as a platelet count≥400,000 µL, and patients were divided into 2 groups according to presence of preoperative thrombocytosis, and the cancer-specific survival rates and overall survival rates of the 2 groups after radical nephrectomy were compared. Results The mean age of the patients was 56.0±11.7 years and the mean follow-up period was 59.3±42.1 months; there were 20 patients with preoperative thrombocytosis. Thirty patients developed metastases and 9 patients died during the follow-up period. In Kaplan-Meier analysis using a univariate log-rank test, both cancer-specific survival rate (p=0.013) and overall survival rate (p=0.012) showed significant association with preoperative thrombocytosis. Controlling for pathological TNM stage, Fuhrman grade and tumor diameter, the Cox proportional hazards model for cancer-specific survival rates showed that preoperative thrombocytosis was an independent prognostic factor (p=0.025). Conclusions Preoperative thrombocytosis was associated with poorer prognosis in patients with nonmetastatic RCC. Thus, preoperative platelet count may be clinically useful for risk stratification of patients undergoing surgery for nonmetastatic RCC.

  1. 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

  2. Lead Clinical and Preclinical Antimalarial Drugs Can Significantly Reduce Sporozoite Transmission to Vertebrate Populations

    PubMed Central

    Upton, L. M.; Brock, P. M.; Churcher, T. S.; Ghani, A. C.; Gething, P. W.; Delves, M. J.; Sala, K. A.; Leroy, D.; Sinden, R. E.

    2014-01-01

    To achieve malarial elimination, we must employ interventions that reduce the exposure of human populations to infectious mosquitoes. To this end, numerous antimalarial drugs are under assessment in a variety of transmission-blocking assays which fail to measure the single crucial criteria of a successful intervention, namely impact on case incidence within a vertebrate population (reduction in reproductive number/effect size). Consequently, any reduction in new infections due to drug treatment (and how this may be influenced by differing transmission settings) is not currently examined, limiting the translation of any findings. We describe the use of a laboratory population model to assess how individual antimalarial drugs can impact the number of secondary Plasmodium berghei infections over a cycle of transmission. We examine the impact of multiple clinical and preclinical drugs on both insect and vertebrate populations at multiple transmission settings. Both primaquine (>6 mg/kg of body weight) and NITD609 (8.1 mg/kg) have significant impacts across multiple transmission settings, but artemether and lumefantrine (57 and 11.8 mg/kg), OZ439 (6.5 mg/kg), and primaquine (<1.25 mg/kg) demonstrated potent efficacy only at lower-transmission settings. While directly demonstrating the impact of antimalarial drug treatment on vertebrate populations, we additionally calculate effect size for each treatment, allowing for head-to-head comparison of the potential impact of individual drugs within epidemiologically relevant settings, supporting their usage within elimination campaigns. PMID:25385107

  3. [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. PMID:7490035

  4. Endocannabinoid system as a regulator of tumor cell malignancy - biological pathways and clinical significance.

    PubMed

    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

  5. Comparison of the activities of the lantibiotics nisin and lacticin 3147 against clinically significant mycobacteria.

    PubMed

    Carroll, James; Draper, Lorraine A; O'Connor, Paula M; Coffey, Aidan; Hill, Colin; Ross, R Paul; Cotter, Paul D; O'Mahony, Jim

    2010-08-01

    The aim of this study was to use the microtitre alamarBlue assay to investigate and compare the antimycobacterial potential of the lantibiotics nisin and lacticin 3147 against a representative cohort of clinically significant mycobacteria, i.e. Mycobacterium tuberculosis H37Ra, Mycobacterium avium subsp. paratuberculosis (MAP) ATCC 19698 and Mycobacterium kansasii CIT11/06. Lacticin 3147 displayed potent activity against all strains of mycobacteria, with MIC(90) values (lowest concentration of lantibiotic that prevented growth of >90% of the bacterial population) of 60 mg/L and 15 mg/L for M. kansasii and MAP, respectively. Lacticin 3147 was particularly effective against M. tuberculosis H37Ra, with a MIC(90) value of 7.5mg/L. Nisin, although inhibitory, was generally less potent against all strains of mycobacteria, with MIC(90) values of 60 mg/L for M. kansasii and >60 mg/L for MAP and M. tuberculosis H37Ra. Thus, lacticin 3147 is a potent antimycobacterial peptide that shows superior activity compared with nisin at physiological pH. PMID:20547041

  6. Expression and clinical significance of glucose transporter-1 in pancreatic cancer

    PubMed Central

    LU, KAI; YANG, JIAN; LI, DE-CHUN; HE, SONG-BING; ZHU, DONG-MING; ZHANG, LI-FENG; ZHANG, XU; CHEN, XIAO-CHEN; ZHANG, BING; ZHOU, JIAN

    2016-01-01

    Increasing evidence has demonstrated that malignant cells exhibit increased glucose uptake, which facilitates survival and growth in a hypoxic environment. The glucose transporter-1 (GLUT-1) is overexpressed in a variety of malignant tumors. However, the association between GLUT-1 expression and clinicopathological factors, 18F-fluorodeoxyglucose uptake and tumor proliferation in pancreatic cancer has not been investigated to date. In the present study, the expression of GLUT-1 in 53 pancreatic cancer tissues was analyzed, which revealed that GLUT-1 was overexpressed in pancreatic tissue and correlated with poor prognosis and clinicopathological characteristics, including increased tumor size, clinical stage and lymph node metastasis, maximum standardized uptake value (SUVmax) and Ki-67 expression. The receiver operating characteristic curve analysis indicated that a cut-off SUVmax value of 4.830 was associated with optimal sensitivity (88%) and specificity (71.4%) for the detection of strong positive GLUT-1 expression. In addition, as the expression of GLUT-1 was found to correlate with Ki-67 expression, GLUT-1 may exhibit a significant effect on cell proliferation in pancreatic cancer. Overall, these findings indicate that GLUT-1 may represent a prognostic indicator, and a potential therapeutic target for pancreatic cancer. PMID:27347132

  7. Nutritional supplements for macular degeneration.

    PubMed

    2006-02-01

    Age-related macular degeneration is the commonest cause of blindness in developed countries and the third most common worldwide. Each year in the UK, around 17,000 people become blind or partially sighted as a result of this condition, and its prevalence is likely to increase with an ageing population. Laser therapy and rarely surgery, can slow disease progression in a minority of patients but is unlikely to restore lost vision. A wide range of nutritional supplements are now on sale with promotional claims that they improve eye health. While some specialists recommend their use to patients with advanced disease, these supplements are also increasingly promoted to people with early or no signs of disease. Consequently, GPs come under pressure from patients to recommend, or even prescribe, a nutritional supplement. Here we examine the evidence for nutritional supplements in the management of age-related macular degeneration and consider which, if any, can be recommended. PMID:16550811

  8. Simplified ultrasound protocol for the exclusion of clinically significant carotid artery stenosis

    PubMed Central

    Högberg, Dominika; Dellagrammaticas, Demosthenes; Kragsterman, Björn; Björck, Martin; Wanhainen, Anders

    2016-01-01

    Objectives To evaluate a simplified ultrasound protocol for the exclusion of clinically significant carotid artery stenosis for screening purposes. Material and methods A total of 9,493 carotid arteries in 4,748 persons underwent carotid ultrasound examination. Most subjects were 65-year-old men attending screening for abdominal aortic aneurysm. The presence of a stenosis on B-mode and/or a mosaic pattern in post-stenotic areas on colour Doppler and maximum peak systolic velocity (PSV) in the internal carotid artery (ICA) were recorded. A carotid stenosis was defined as The North American Symptomatic Carotid Endarterectomy Trial (NASCET) >20% and a significant stenosis as NASCET >50%. The kappa (κ) statistic was used to assess agreement between methods. Sensitivity, specificity, positive predictive (PPV), and negative predictive (NPV) values were calculated for the greyscale/mosaic method compared to conventional assessment by means of PSV measurement. Results An ICA stenosis was found in 121 (1.3%) arteries; 82 (0.9%) were graded 20%–49%, 16 (0.2%) were 50%–69%, and 23 (0.2%) were 70%–99%. Eighteen (0.2%) arteries were occluded. Overall, the greyscale/mosaic protocol showed a moderate agreement with ICA PSV measurements for the detection of carotid artery stenosis, κ = 0.455. The sensitivity, specificity, PPV, and NPV for detection of >20% ICA stenosis were 91% (95% CI 0.84–0.95), 97% (0.97–0.98), 31% (0.26–0.36), and 97% (0.97–0.97), respectively. The corresponding figures for >50% stenosis were 90% (0.83–0.95), 97% (0.97–0.98), 11% (0.08–0.15), and 100% (0.99–1.00). Conclusion Compared with PSV measurements, the simplified greyscale/mosaic protocol had a high negative predictive value for detection of >50% carotid stenosis, suggesting that it may be suitable as a screening method to exclude significant disease. PMID:27379448

  9. Aqueous Levels of Pigment Epithelium-Derived Factor and Macular Choroidal Thickness in High Myopia

    PubMed Central

    Chen, Wei; Guan, Yubo; He, Guanghui; Li, Zhiwei; Song, Hui; Xie, Shiyong; Han, Quanhong

    2015-01-01

    Purpose. To investigate the correlation between aqueous and serum levels of pigment epithelium-derived factor (PEDF) and macular choroidal thickness in high myopia patients, both with and without choroidal neovascularization (CNV). Methods. Serum and aqueous levels of PEDF were measured by enzyme-linked immunosorbent assay in 36 high myopia patients (36 eyes) with no CNV (non-CNV group), 14 high myopia patients (14 eyes) with CNV (CNV group), and 42 nonmyopia patients (42 eyes) (control group). Macular choroidal thickness was measured by enhanced-depth imaging optical coherence tomography. Results. Aqueous levels of PEDF were significantly higher in CNV group compared with non-CNV (P < 0.001) and control (P < 0.001) groups. Macular choroidal thicknesses were significantly decreased in the non-CNV and CNV groups compared with the control (P < 0.001) group. A statistically significant difference (P = 0.012) was found between the CNV and non-CNV groups. There was a positive correlation between aqueous PEDF and macular choroidal thickness in the non-CNV group (P = 0.005), but no correlation with the CNV group. No correlation between serum PEDF and macular choroidal thickness was detected in the three groups. Conclusion. Variations in aqueous PEDF levels coincide with changes in macular choroidal thickness in high myopia patients with no CNV, while no such relationship exists in high myopia patients with CNV. PMID:26491554

  10. VMD2 mutations in vitelliform macular dystrophy (Best disease) and other maculopathies.

    PubMed

    White, K; Marquardt, A; Weber, B H

    2000-01-01

    Mutations in the gene VMD2 are associated with autosomal dominant vitelliform macular dystrophy (Best disease). VMD2 is expressed in the retinal pigment epithelium and codes for a 585 amino acid putative transmembrane protein with undetermined functional properties. To date, 48 different mutations, predominantly missense, have been described in Best disease families. These mutations generally affect amino acids in the first 50% of the protein, and occur in four distinct clusters possibly representing regions of functional importance. VMD2 has also been investigated in other macular diseases. Mutations have been documented in a significant percentage of patients with adult vitelliform macular dystrophy (AVMD) and in a single case of "bull's-eye" maculopathy. Results of analysis in two large series of individuals with age-related macular degeneration (AMD) suggest that VMD2 does not play a major role in this prevalent disorder. PMID:10737974

  11. [Neurotrophic keratopathy--studies on substance P and the clinical significance of corneal sensation].

    PubMed

    Nishida, T; Nakamura, M; Konma, T; Ofuji, K; Nagano, K; Tanaka, T; Enoki, M; Reid, T W; Brown, S M; Murphy, C J; Mannis, M J

    1997-12-01

    Neurotrophic keratopathy, which often follows damage to the trigeminal nerve, is clinically characterized by various types of epithelial disorders and melting of corneal stroma. To understand both the pathology of neurotrophic keratopathy and the physiological significance of corneal sensation, we investigated both the cellular and molecular functions of a sensory neurotransmitter, substance P, in corneal epithelial cells. Our findings prompted us to try a new mode of treatment for neurotrophic keratopathy. Substance P, a member of the tachykinin family, is an 11-amino-acid peptide. In an organ culture system using rabbit corneas, substance P alone had no effect on corneal epithelial migration. In the presence of insulin-like growth factor-1 (IGF-1), however, substance P synergistically facilitated corneal epithelial migration in proportion to the concentration of substance P or of IGF-1. Other neurotransmitters (acetylcholine, norepinephrine, serotonin etc.) or tachykinins (neurokinin A, eledoisin etc.) did not show this synergistic effect with IGF-1. Among receptors for the tachykinin family (NK-1, NK-2, or NK-3) only the NK-1 receptor system was involved in the synergistic effect of substance P and IGF-1 on corneal epithelial migration. IGF-1 affected neither the binding constant nor the number of sites of substance P receptors in corneal epithelial cells, suggesting that the synergistic effect was not regulated at the receptor level. Various extracellular signals activate the intracellular signal transduction system, thus amplifying specific biological functions. We found that the addition of inhibitors of protein kinase C or tyrosine kinase clearly inhibited the synergistic effect of substance P and IGF-1 on corneal epithelial migration, demonstrating that protein kinase C and tyrosine kinase are involved in the synergistic effect. During corneal epithelial wound healing, epithelial cells must attach to a provisional, extracellular fibronectin matrix. We

  12. Transfusion of murine RBCs expressing the human KEL glycoprotein induces clinically significant alloantibodies

    PubMed Central

    Stowell, Sean R.; Girard-Pierce, Kathryn R.; Smith, Nicole H.; Henry, Kate L.; Arthur, C. Maridith; Zimring, James C.; Hendrickson, Jeanne E.

    2013-01-01

    Background Red blood cell (RBC) alloantibodies to non-self antigens may develop following transfusion or pregnancy, leading to morbidity and mortality in the form of hemolytic transfusion reactions or hemolytic disease of the newborn. A better understanding of the mechanisms of RBC alloantibody induction, or strategies to mitigate the consequences of such antibodies, may ultimately improve transfusion safety. However, such studies are inherently difficult in humans. Study Design and Methods We recently generated transgenic mice with RBC specific expression of the human KEL glycoprotein, with the KEL2 or KEL1 antigens. Herein, we investigate recipient alloimmune responses to transfused RBCs in this system. Results Transfusion of RBCs from KEL2 donors into wild type recipients (lacking the human KEL protein but expressing the murine KEL orthologue) resulted in dose dependent anti-KEL glycoprotein IgM and IgG antibody responses, enhanced by recipient inflammation with poly (I:C). Boostable responses were evident upon repeat transfusion, with morbid appearing alloimmunized recipients experiencing rapid clearance of transfused KEL2 but not control RBCs. Although KEL1 RBCs were also immunogenic following transfusion into wild type recipients, transfusion of KEL1 RBCs into KEL2 recipients or vice versa failed to lead to detectable anti-KEL1 or anti-KEL2 responses. Conclusions This murine model, with reproducible and clinically significant KEL glycoprotein alloantibody responses, provides a platform for future mechanistic studies of RBC alloantibody induction and consequences. Long term translational goals of these studies include improving transfusion safety for at risk patients. PMID:23621760

  13. 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

  14. Clinical and prognostic significance of lung thallium uptake on rest imaging in acute myocardial infarction

    SciTech Connect

    Jain, D.; Lahiri, A.; Raftery, E.B. )

    1990-01-15

    Exercise-induced pulmonary uptake of thallium-201 in patients with ischemic heart disease is probably due to transient pulmonary edema and left ventricular failure induced by exercise. The significance of increased lung uptake of thallium-201 at rest after acute myocardial infarction (AMI) has not been described. Ninety-six patients admitted with chest pain for suspected AMI or unstable angina underwent thallium-201 imaging at rest. Using conventional diagnostic criteria, 62 had AMI, 12 had unstable angina and 22 had neither. Increased lung uptake of thallium-201 was present in 24 of the total 96 (25%) patients, 20 of the 62 (32%) patients with AMI and 4 of 34 (13%) patients with no evidence of infarction. In the AMI group, those with increased lung thallium-201 uptake had a higher mean +/- standard deviation segmental thallium-201 defect score (22 +/- 7 vs 12 +/- 8, p less than 0.0001), lower ejection fraction (35 +/- 14 vs 49 +/- 14%, p less than 0.002), higher peak creatine kinase levels (2,410 +/- 1,247 vs 1,496 +/- 1,228 IU/liter, p less than 0.01), higher wall motion abnormality score (25 +/- 13 vs 13 +/- 12, p less than 0.0001), increased incidence of clinical in-hospital heart failure (15 of 20 vs 7 of 42, p less than 0.0001) and higher short-term mortality (4 of 20 vs 1 of 42, p less than 0.02) compared to those without increased lung thallium-201 uptake.

  15. Selection of human p75NTR tag SNPs and its biological significance for clinical association studies.

    PubMed

    Wang, Yong-Tang; Lu, Xiu-Min; Shu, Ya-Hai; Xiao, Lan; Chen, Kai-Ting

    2014-01-01

    To select tag single nucleotide polymorphisms (SNPs) within and around human p75 neurotrophin receptor (p75NTR) gene in Chinese Han population, the sequence involving p75NTR gene as well as the upstream and downstream of the gene was identified according to the data from National Center for Biotechnology Information (NCBI) GenBank database, and the SNP genotype data involving 63 SNPs in the regions were obtained from Chinese Han Beijing (CHB) population of HapMap database. Then, Haploview (version 4.2) was used to calculate linkage disequilibrium (LD) statistics for the selected 32 common SNPs with a minor allele frequence (MAF) more than 0.05. Haplotype blocks were constructed throughout the p75NTR gene according to the upper and the lower 95% confidence bound of D' value, and the tag SNPs were selected based on the r2 and LOD values between SNPs as well as the results of bioinformatics analysis. The results indicated that five haplotype blocks were constructed within and around p75NTR gene and 12 tag SNPs including rs2537710, rs603769, rs614455, rs2537706, rs534561, rs2072445, rs2072446, rs7219709, rs734194, rs741071, rs741073 and rs2671641 were selected to represent the other 51 SNPs in p75NTR gene. Therefore, the 12 selected SNPs may act as tag SNPs for the entire p75NTR gene in Chinese Han population, which will provide an effective way to select tag SNPs in a whole gene, and its biological significance is to further guide the clinical association studies between the candidate gene and disease susceptibility. PMID:25227100

  16. A clinical algorithm for triaging patients with significant lymphadenopathy in primary health care settings in Sudan

    PubMed Central

    El Hag, Imad A.; Elsiddig, Kamal E.; Elsafi, Mohamed E.M.O; Elfaki, Mona E.E.; Musa, Ahmed M.; Musa, Brima Y.; Elhassan, Ahmed M.

    2013-01-01

    Abstract Background Tuberculosis is a major health problem in developing countries. The distinction between tuberculous lymphadenitis, non-specific lymphadenitis and malignant lymph node enlargement has to be made at primary health care levels using easy, simple and cheap methods. Objective To develop a reliable clinical algorithm for primary care settings to triage cases of non-specific, tuberculous and malignant lymphadenopathies. Methods Calculation of the odd ratios (OR) of the chosen predictor variables was carried out using logistic regression. The numerical score values of the predictor variables were weighed against their respective OR. The performance of the score was evaluated by the ROC (Receiver Operator Characteristic) curve. Results Four predictor variables; Mantoux reading, erythrocytes sedimentation rate (ESR), nocturnal fever and discharging sinuses correlated significantly with TB diagnosis and were included in the reduced model to establish score A. For score B, the reduced model included Mantoux reading, ESR, lymph-node size and lymph-node number as predictor variables for malignant lymph nodes. Score A ranged 0 to 12 and a cut-off point of 6 gave a best sensitivity and specificity of 91% and 90% respectively, whilst score B ranged -3 to 8 and a cut-off point of 3 gave a best sensitivity and specificity of 83% and 76% respectively. The calculated area under the ROC curve was 0.964 (95% CI, 0.949 – 0.980) and -0.856 (95% CI, 0.787 - 0.925) for scores A and B respectively, indicating good performance. Conclusion The developed algorithm can efficiently triage cases with tuberculous and malignant lymphadenopathies for treatment or referral to specialised centres for further work-up.

  17. Clinical significance of changes in the corrected QT interval in stress-induced cardiomyopathy

    PubMed Central

    Lee, Jung-Hee; Uhm, Jae-Sun; Shin, Dong Geum; Joung, Boyoung; Pak, Hui-Nam; Ko, Young-Guk; Hong, Geu-Ru; Lee, Moon-Hyoung

    2016-01-01

    Background/Aims: Although transient changes in the electrocardiogram (ECG) of patients with stress-induced cardiomyopathy (SCMP) are common, there are little data about ECG changes in patients with SCMP and the clinical implications of these variations. Methods: We investigated a total of 128 patients (age, 63.2 ± 15.4 years; female, 60.9%) diagnosed with SCMP. We compared the ECGs taken after SCMP diagnosis and during the recovery phase to those taken before SCMP diagnosis under baseline conditions. All patients were divided into two groups according to corrected QT (QTc) interval changes: recovered QTc group (QTc in SCMP > QTc in recovery phase, n = 77) and nonrecovered QTc group (QTc in SCMP ≤ QTc in recovery phase, n = 51). Results: In comparison of baseline, SCMP, and recovery phase, we found the mean heart rate (81.5 ± 18.7, 96.8 ± 25.3, and 83.0 ± 19.4/min, respectively; p < 0.001), frequencies of ST segment elevation (0.0%, 8.6%, and 1.6%, p = 0.004), ST segment depression (0.0%, 6.3%, and 1.6%, p = 0.007), T wave inversion (4.4 %, 43.8%, and 61.7%, p < 0.001), and QTc (447.4 ± 35.3, 488.9 ± 67.1, and 468.0 ± 49.5, p < 0.001) showed significant changes. In-hospital mortality (9.1% vs. 25.5%, p = 0.012) and critical care (54.5% vs. 72.5%, p = 0.040) occurred more frequently in the nonrecovered QTc group than in recovered QTc group. Conclusions: The QTc can be prolonged in patients with SCMP. Short-term mortality was increased in patients where the QTc did not recover. PMID:27052264

  18. Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma

    PubMed Central

    Yu, Ji-wei; Wu, Ju-gang; Zheng, Lin-hai; Zhang, Biao; Ni, Xiao-chun; Li, Xiao-qiang; Jiang, Bo-jian

    2009-01-01

    Background To investigate influencing factors of the metastatic lymph nodes ratio (MLR) and whether it is related to survival in patients with gastric adenocarcinoma. Methods We retrospectively evaluated the clinical features of 121 patients with gastric adenocarcinoma enrolled in our hospital between 2000 and 2007. The receiver operating characteristic (ROC) curve was used to determine the cutoff of the MLR, and CK20 immunohistochemical staining was used to detect micrometastasis of the lymph nodes. Results The areas under the ROC curve of MLR used to predict the death of 3-year and 5-year postoperative patients were 0.826 ± 0.053 and 0.896 ± 0.046. Thus MLR = 30.95% and MLR = 3.15% were designated as cutoffs. The MLR was then classified into three groups: MLR1 (MLR<3.15%); MLR2(3.15% ≤ MLR ≤ 30.95%); and MLR3 (MLR>30.95%). We found that patients with a higher MLR demonstrated a much poorer survival period after radical operation than those patients with a lower MLR (P = 0.000). The COX model showed that MLR was an independent prognostic factor (P = 0.000). The MLR could also discriminate between subsets of patients with different 5-year survival periods within the same N stage (P < 0.05). The MLR has been shown to be 34.7% (242/697) by HE staining and 43.5% (303/697) by CK staining (P = 0.001). The clinicopathological characteristics of lymph vessel invasion and the depth of invasion could significantly affect the MLR. Conclusion MLR is an independent prognostic factor in gastric cancer. The combined ROC curve with MLR is an effective strategy to produce a curve to predict the 3-year and 5-year survival rates. PMID:19393100

  19. Decreased expression of hsa_circ_001988 in colorectal cancer and its clinical significances

    PubMed Central

    Wang, Xuning; Zhang, Yue; Huang, Liang; Zhang, Jiajin; Pan, Fei; Li, Bing; Yan, Yongfeng; Jia, Baoqing; Liu, Hongyi; Li, Shiyou; Zheng, Wei

    2015-01-01

    Circular RNA (circRNA) is a type of RNAs which, unlike the better known linear RNA, forms a covalently closed continuous loop. They have emerged recently as a new player in governing fundamental biological processes. However it remains elusive about the correlation of hsa_circ_001988 abundance with colorectal cancer. To investigate the circular RNA expression in colorectal cancer, the targeted hsa_circ_001988 was selected from next generation sequence data base generated in house and then designed divergent primers to amplify hsa_circ_001988 and sequenced it for validation. The expression of hsa_circ_001988 in 31 matched colorectal cancer tissue and normal colon mucosa was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). We used ΔCt method and investigated the differences between tumor tissues and normal colon mucosa by paired t-test. One-way analysis of variance was conducted to analyze the relationship between hsa_circ_001988 expression level and clinic pathological factors of patients. Receiver operating characteristic (ROC) curve was built by SPSS to evaluate the diagnostic values. The expression of hsa_circ_001988 was significantly correlated with differentiation (P<0.05) and perineural invasion (P<0.05). The area under ROC curve of hsa_circ_001988 was 0.788 (P<0.05). Those results indicate that hsa_circ_001988 may become a novel potential biomarker in the diagnosis of colorectal cancer and a potential novel target for the treatment of colorectal cancer. PMID:26884878

  20. Clinical Significance of a Point Mutation in DNA Polymerase Beta (POLB) Gene in Gastric Cancer

    PubMed Central

    Tan, Xiaohui; Wang, Hongyi; Luo, Guangbin; Ren, Shuyang; Li, Wenmei; Cui, Jiantao; Gill, Harindarpal S.; Fu, Sidney W.; Lu, Youyong

    2015-01-01

    Gastric cancer (GC) is a major cause of global cancer mortality. Genetic variations in DNA repair genes can modulate DNA repair capability and, consequently, have been associated with risk of developing cancer. We have previously identified a T to C point mutation at nucleotide 889 (T889C) in DNA polymerase beta (POLB) gene, a key enzyme involved in base excision repair in primary GCs. The purpose of this study was to evaluate the mutation and expression of POLB in a larger cohort and to identify possible prognostic roles of the POLB alterations in GC. Primary GC specimens and their matched normal adjacent tissues were collected at the time of surgery. DNA, RNA and protein samples were isolated from GC specimens and cell lines. Mutations were detected by PCR-RFLP/DHPLC and sequencing analysis. POLB gene expression was examined by RT-PCR, tissue microarray, Western blotting and immunofluorescence assays. The function of the mutation was evaluated by chemosensitivity, MTT, Transwell matrigel invasion and host cell reactivation assays. The T889C mutation was detected in 18 (10.17%) of 177 GC patients. And the T889C mutation was associated with POLB overexpression, lymph nodes metastases and poor tumor differentiation. In addition, patients with- the mutation had significantly shorter survival time than those without-, following postoperative chemotherapy. Furthermore, cell lines with T889C mutation in POLB gene were more resistant to the treatment of 5-fluorouracil, cisplatin and epirubicin than those with wild type POLB. Forced expression of POLB gene with T889C mutation resulted in enhanced cell proliferation, invasion and resistance to anticancer drugs, along with increased DNA repair capability. These results suggest that POLB gene with T889C mutation in surgically resected primary gastric tissues may be clinically useful for predicting responsiveness to chemotherapy in patients with GC. The POLB gene alteration may serve as a prognostic biomarker for GC. PMID

  1. 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

  2. Dark adaptation in patients with Best vitelliform macular dystrophy.

    PubMed Central

    Baca, W; Fishman, G A; Alexander, K R; Glenn, A M

    1994-01-01

    Psychophysical dark adaptation studies were performed in six patients with Best vitelliform macular dystrophy (BVMD) using a Goldmann-Weekers dark adaptometer. Prebleach thresholds were determined before obtaining a postbleach full recovery curve. Unlike patients with Stargardt macular dystrophy, all patients with BVMD showed a normal time to reach their baseline dark adapted thresholds after bleaching of their rod visual pigment when tested in clinically normal appearing retina. Although a lipofuscin material accumulates within retinal pigment epithelial cells in patients with either Best or Stargardt dystrophy, functional findings pertaining to recovery of rod dark adaptation thresholds as well as electro-oculogram light peak to dark trough ratios are different in these two disorders. PMID:8060924

  3. Dark adaptation in patients with Best vitelliform macular dystrophy.

    PubMed

    Baca, W; Fishman, G A; Alexander, K R; Glenn, A M

    1994-06-01

    Psychophysical dark adaptation studies were performed in six patients with Best vitelliform macular dystrophy (BVMD) using a Goldmann-Weekers dark adaptometer. Prebleach thresholds were determined before obtaining a postbleach full recovery curve. Unlike patients with Stargardt macular dystrophy, all patients with BVMD showed a normal time to reach their baseline dark adapted thresholds after bleaching of their rod visual pigment when tested in clinically normal appearing retina. Although a lipofuscin material accumulates within retinal pigment epithelial cells in patients with either Best or Stargardt dystrophy, functional findings pertaining to recovery of rod dark adaptation thresholds as well as electro-oculogram light peak to dark trough ratios are different in these two disorders. PMID:8060924

  4. Anti-VEGF therapy for diabetic macular edema.

    PubMed

    Stewart, Michael W

    2014-08-01

    Vascular endothelial growth factor (VEGF) plays a pivotal role in the development of diabetic macular edema (DME), the leading cause of vision loss among working-aged individuals. A decade of clinical trials demonstrated that drugs that bind soluble VEGF restore the integrity of the blood-retinal barrier, resolve macular edema, and improve vision in most patients with DME. Four drugs (pegaptanib, ranibizumab, bevacizumab, and aflibercept) effectively treat DME when administered by intravitreal injections. Only ranibizumab has received U.S. Food and Drug Administration (FDA) approval for DME, but bevacizumab is commonly used off-label, and an FDA application for aflibercept is pending. Effective treatment requires repeated injections, although recent data suggest that the treatment burden diminishes after 1 year. Intravitreal therapy is generally safe, although the incidence of systemic thromboembolic events varies among trials. PMID:24919750

  5. Expression and clinical significance of SALL4 and β-catenin in colorectal cancer.

    PubMed

    Hao, Liliang; Zhao, Yan; Wang, Zhen; Yin, Hongzhuan; Zhang, Xin; He, Tao; Song, Shanshan; Sun, Shaolong; Wang, Baosheng; Li, Zhijie; Su, Qi

    2016-04-01

    Previous studies on the expression of Sal-like 4 (SALL4), a zinc finger transcription factor, had conflicting results in colorectal cancer (CRC). The main aim of this study was to investigate the expression of SALL4 and its relationship with β-catenin in CRC. Immunohistochemistry was performed to examine the expression of SALL4 and β-catenin in a cohort of 149 patients with CRC, 12 with atypical hyperplasia, 25 with benign tumor and 38 with normal tissue. Expression patterns of SALL4 and β-catenin and correlation with clinicopathological features were investigated. The relationship between SALL4 and β-catenin was examined by immunofluorescence and co-immunoprecipitation using CRC cell lines, SW480, SW620, HCT116 and HT29. Immunohistochemical analysis revealed significantly lower expression of SALL4 in CRC (46.3 %) than atypical hyperplasia (68.0 %, p < 0.05) and normal tissue (78.9 %, p < 0.01). Well-differentiated CRC seemed to express more SALL4 (47.6 %) than moderately (45.8 %) and poorly-differentiated cancers (18.8 %) (p < 0.05). However, SALL4 expression positively correlated with lymph node metastasis and tumor-node-metastasis (TNM) and Dukes stages (all p < 0.05) suggesting a new mechanism involved in the function of SALL4 in CRC. β-catenin was expressed significantly higher in CRC (69.1 %) than normal tissue (21.1 %, p < 0.01), and positively correlated with CA19-9 level in serum (p < 0.05). SALL4 and β-catenin were positively correlated in CRC (Spearman correlation coefficient R = 0.536, p < 0.01). The group of co-expression of the two molecules showed advanced lymph node metastasis, TNM stage and Dukes stage (all p < 0.05). Double-labeling immunofluorescence and co-immunoprecipitation indicated that SALL4 and β-catenin co-localized in the nucleus and cytoplasm and interacted. Taken together, our results revealed that SALL4 and β-catenin were positively correlated in CRC. In CRC cells, SALL4 and β-catenin co-localized and interacted. The function

  6. Clinical significance of SPRR1A expression in progesterone receptor-positive breast cancer.

    PubMed

    Chen, Guanglei; Li, Gang; Luo, Minna; Wei, Xiaofei; Wang, Dan; Zhang, Hao; Zhao, Xinhan; Chen, Bo; Liu, Caigang

    2015-04-01

    Small proline-rich repeat protein 1A (SPRR1A) is a marker for terminal squamous cell differentiation. Previous studies showed that SPRR1A expression increases in squamous cell carcinoma of the skin, but decreases in esophageal squamous cell carcinoma. This study focuses on the expression of SPRR1A protein in breast cancers (BCs) in China. A total of 111 patients with histologically confirmed BC, who underwent radical surgery between January 2006 and September 2007 in China Medical University, were enrolled. The relationship between SPRR1A expression and clinicopathological factors as well as BC prognoses was also determined. Overall, SPRR1A expression was detected in more than half of the BC specimens by immunohistochemistry (56/111, 53.8%), but there was no significant difference between age groups (≥50 vs. <50 years) in terms of SPRR1A expression (P = 0.915), as well as no differences between SPRR1A expression and the clinical stage (0-I vs. II-III) or nodal status (P = 0.234 and 0.632, respectively). Moreover, human epidermal growth factor receptor 2 overexpression was not correlated with SPRR1A expression, whereas Ki67 was associated with SPRR1A expression (P = 0.155 and 0.028, respectively). Interestingly, SPRR1A expression was significantly associated with progesterone receptor-positive (P = 0.010) rather than estrogen receptor-positive (0.778) BCs. The 5-year survival rate in patients did not differ with the presence or absence of SPRR1A expression (P = 0.753), whereas the combination of SPRR1A expression, progesterone receptor status, and menopausal status allowed identification of a subgroup of BC patients with a good long-term prognosis. Thus, the SPRR1A status might play an important role in the prognosis of postmenopausal breast carcinoma patients, especially that of progesterone receptor-positive subgroups. PMID:25424702

  7. 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

  8. 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

  9. Reading performance with various lamps in age-related macular degeneration.

    PubMed

    Eperjesi, F; Maiz-Fernandez, C; Bartlett, H E

    2007-01-01

    The purpose of this study was to determine if there was an objective difference in reading between four commonly available lamps, of varying spectral radiance, for 13 subjects with age-related maculopathy (ARM) or non-exudative age-related macular degeneration (AMD)--logMAR visual acuity between 0.04 and 0.68. At a constant illuminance of 2000 lux, there was no interaction between ARM and AMD subgroups and no statistically significant difference between the lamps: standard (clear envelope) incandescent, daylight simulation (blue tint envelope) incandescent, compact fluorescent and halogen incandescent, for any reading outcome measure (threshold print size p = 0.67, critical print size p = 0.74, acuity reserve p = 0.84 and mean reading rate p = 0.78). For lamps typically used in low-vision rehabilitation, a clinically significant effect of spectral radiance on reading for people with ARM or non-exudative AMD is unlikely. PMID:17239195

  10. 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.

  11. Kilovoltage radiosurgery with gold nanoparticles for neovascular age-related macular degeneration (AMD): a Monte Carlo evaluation.

    PubMed

    Brivio, D; Zygmanski, P; Arnoldussen, M; Hanlon, J; Chell, E; Sajo, E; Makrigiorgos, G M; Ngwa, W

    2015-12-21

    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. PMID:26576672

  12. De Garengeot's hernia in an 82-year-old man: a case report and clinical significance.

    PubMed

    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

  13. Cell and tissue interactions in carcinogenesis and metastasis and their clinical significance.

    PubMed

    Tarin, David

    2011-04-01

    This review describes a new vision for future directions in the study of metastatic cancer biology and pathology. It is based upon clinical and experimental observations on the constituent cell lineages within a neoplasm and on tumour-host interactions. The vision incorporates information from studies in population biology, developmental biology and experimental pathology as well as investigations upon human malignant disease. The assembled information reveals that invasion and metastasis are supra-cellular manifestations of "emergent behavior" among combinations of normal and malignant cell lineages in vivo. Emergent behavior is a combinatorial interactive process in which a population displays new traits which cannot be achieved by individuals acting separately and which subside when the specific population mix disaggregates. Disruption of such pathological interactions in the field of a developing primary or secondary tumour is, therefore, required to disable the malignant population and arrest progression without tissue destruction. These conclusions originate, in part, from principles which govern the sociobiology and group behavior of bees, ants, fish, birds and human societies. In all these social organisms, external factors can disrupt signaling mechanisms and induce expanding self-perpetuating rogue behavior, leading to social disintegration. These principles also apply to cellular societies composing higher animals, which likewise need intrinsic rules to maintain social order and avoid anarchy, and recognition of this is essential for advancing future research on the mechanisms involved in carcinogenesis and metastasis. Summarised evidence is presented here to support the conclusion that miscommunications between cells and tissues in the region of the developing tumour and its metastases are the main direct perpetrators of malignant disease. Genetic lesions (mutations, deletions, translocations, reduplications, etc.), commonly seen in cancers, can

  14. Clinical conditions and patient factors significantly influence diagnostic utility of D-dimer in venous thromboembolism.

    PubMed

    Qasim, Asghar; Duggan, Mary; O'Connell, Niamh; O'Driscoll, Anne

    2009-06-01

    Determining D-dimer levels remains important in the diagnostic algorithms for venous thromboembolism (VTE). The present study aimed to identify factors influencing D-dimer utility in diagnosing VTE. Consecutive symptomatic medical patients, who attended our emergency department from 1 November 2006 to 31 December 2006, had D-dimer levels measured as fibrinogen equivalent units (FEU), following clinical risk assessment. Diagnosis of VTE was established by venous compression ultrasonography and computed tomographic pulmonary angiography. VTE-negative patients were followed for 2 months to detect future occurrence of thromboembolism. Impact of various factors on D-dimer levels was analyzed. Four thousand and twenty-six patients attended our emergency department, and 525 patients (median age 52 years) had D-dimer assessed. Final diagnosis of VTE was established in 25 (4.7%) patients on radiological investigations. Median D-dimer levels for VTE-negative patients less than 60 years old, with normal renal function and chest radiology were 0.38 microgFEU/ml (range 0.19-2.3), 0.39 microgFEU/ml (range 0.17-3.5) and 0.39 microgFEU/ml (range 0.1-4.3), respectively. Similar figures for those at least 60 years, with renal impairment and abnormal chest radiology, were 0.75 microgFEU/ml (range 0.22-4.3), 0.52 microgFEU/ml (range 0.17-4.4) and 0.92 microgFEU/ml (range 0.26-5.6), respectively. Factors including patient age, renal function and chest radiology had significant influence on D-dimer levels (P < 0.01). A triad of patient age at least 60 years, renal impairment (modification of diet in renal disease stage 2-5) and abnormal chest radiology had a false positive D-dimer in 96% of patients (n = 72). Use of D-dimer in patients with a triad of advanced age, renal impairment and abnormal chest radiology has no practical diagnostic value in VTE. PMID:19276796

  15. Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance.

    PubMed

    Saunus, Jodi M; Quinn, Michael C J; Patch, Ann-Marie; Pearson, John V; Bailey, Peter J; Nones, Katia; McCart Reed, Amy E; Miller, David; Wilson, Peter J; Al-Ejeh, Fares; Mariasegaram, Mythily; Lau, Queenie; Withers, Teresa; Jeffree, Rosalind L; Reid, Lynne E; Da Silva, Leonard; Matsika, Admire; Niland, Colleen M; Cummings, Margaret C; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Anderson, Matthew J; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Kassahn, Karin S; Narayanan, Vairavan; Taib, Nur Aishah; Teo, Soo-Hwang; Chow, Yock Ping; kConFab; Jat, Parmjit S; Brandner, Sebastian; Flanagan, Adrienne M; Khanna, Kum Kum; Chenevix-Trench, Georgia; Grimmond, Sean M; Simpson, Peter T; Waddell, Nicola; Lakhani, Sunil R

    2015-11-01

    Treatment options for patients with brain metastases (BMs) have limited efficacy and the mortality rate is virtually 100%. Targeted therapy is critically under-utilized, and our understanding of mechanisms underpinning metastatic outgrowth in the brain is limited. To address these deficiencies, we investigated the genomic and transcriptomic landscapes of 36 BMs from breast, lung, melanoma and oesophageal cancers, using DNA copy-number analysis and exome- and RNA-sequencing. The key findings were as follows. (a) Identification of novel candidates with possible roles in BM development, including the significantly mutated genes DSC2, ST7, PIK3R1 and SMC5, and the DNA repair, ERBB-HER signalling, axon guidance and protein kinase-A signalling pathways. (b) Mutational signature analysis was applied to successfully identify the primary cancer type for two BMs with unknown origins. (c) Actionable genomic alterations were identified in 31/36 BMs (86%); in one case we retrospectively identified ERBB2 amplification representing apparent HER2 status conversion, then confirmed progressive enrichment for HER2-positivity across four consecutive metastatic deposits by IHC and SISH, resulting in the deployment of HER2-targeted therapy for the patient. (d) In the ERBB/HER pathway, ERBB2 expression correlated with ERBB3 (r(2)  = 0.496; p < 0.0001) and HER3 and HER4 were frequently activated in an independent cohort of 167 archival BM from seven primary cancer types: 57.6% and 52.6% of cases were phospho-HER3(Y1222) or phospho-HER4(Y1162) membrane-positive, respectively. The HER3 ligands NRG1/2 were barely detectable by RNAseq, with NRG1 (8p12) genomic loss in 63.6% breast cancer-BMs, suggesting a microenvironmental source of ligand. In summary, this is the first study to characterize the genomic landscapes of BM. The data revealed novel candidates, potential clinical applications for genomic profiling of resectable BMs, and highlighted the possibility of therapeutically targeting

  16. [New drug VEGF Trap-Eye--Eylea--and its use in the treatment of age-related macular degeneration, central retinal vein occlusion, diabetic macular edema, and choroidal neovascularization secondary to pathologic myopia].

    PubMed

    Rejdak, Robert; Szkaradek, Małgorzata; Taslaq, Wesam; Kałuzny, Jakub J; Grieb, Pawel; Jünemann, Anselm G M

    2012-01-01

    Vascular endothelial growth factor (VEGF) plays an important role in the pathogenesis of choroidal and retinal neovascularization. Anti-VEGF therapy changed the standard-of-care for ocular disease with neovascularisation. This article presents one promising new drug--VEGF Trap-Eye--and results of clinical trials evaluating its efficacy in the treatment of wet age-related macular degeneration, central retinal vain occlusion, diabetic macular edema and choroidal neovascularization secondary to pathologic myopia. PMID:23461161

  17. Outer Retinal Structure in Best Vitelliform Macular Dystrophy

    PubMed Central

    Kay, David B.; Land, Megan E.; Cooper, Robert F.; Dubis, Adam M.; Godara, Pooja; Dubra, Alfredo; Carroll, Joseph; Stepien, Kimberly E.

    2014-01-01

    Objective To characterize outer retinal structure in Best Vitelliform Macular Dystrophy (BVMD), using spectral domain optical coherence tomography (SD-OCT) and adaptive optics scanning light ophthalmoscopy (AOSLO). Methods Four symptomatic members of a family with BVMD with known BEST1 gene mutation were recruited. Thickness of two outer retinal layers corresponding to photoreceptor inner and outer segments were measured using SD-OCT. Photoreceptor mosaic AOSLO images within and around visible lesions were obtained, and cone density was assessed in two subjects. Results Each subject was at a different stage of BVMD, with photoreceptor disruption evident by AOSLO at all stages. When comparing SD-OCT and AOSLO images from the same location, AOSLO images allowed for direct assessment of photoreceptor structure. A variable degree of retained photoreceptors was seen within all lesions. The photoreceptor mosaic immediately adjacent to visible lesions appeared contiguous and was of normal density. Fine hyperreflective structures were visualized by AOSLO, and their anatomical orientation and size are consistent with Henle fibers. Conclusions AOSLO findings indicate substantial photoreceptor structure persists within active lesions, accounting for good visual acuity in these patients. Despite previous reports of diffuse photoreceptor outer segment abnormalities in BVMD, our data reveal normal photoreceptor structure in areas adjacent to clinical lesions. Clinical Relevance This study demonstrates the utility of AOSLO for understanding the spectrum of cellular changes that occur in inherited degenerations such as BVMD. Photoreceptors are often significantly affected at various stages of inherited degenerations, and these changes may not be readily apparent with current clinical imaging instrumentation. PMID:23765342

  18. Retinal Crystals in Type 2 Idiopathic Macular Telangiectasia

    PubMed Central

    Sallo, Ferenc B; Leung, Irene; Chung, Mina; Wolf-Schnurrbusch, Ute EK; Dubra, Alfredo; Williams, David R; Clemons, Traci; Pauleikhoff, Daniel; Bird, Alan C; Peto, Tunde

    2012-01-01

    Purpose To characterize the phenotype and investigate the associations of intraretinal crystalline deposits in a large cohort of Type 2 Idiopathic Macular Telangiectasia (MacTel) Design Case-control study Participants Patients with and without retinal crystals from the Macular Telangiectasia Project, an international multi-centre prospective study of Type 2 MacTel. Methods Grading of stereoscopic 30° colour fundus (CF), confocal blue light reflectance (CBR), red-free (RF) and infrared (IR) images was performed according to the MacTel Natural History Study protocol and staged using the classification system devised by Gass & Blodi. SD-OCT and adaptive optics imaging were used for a finer analysis of the phenotype. Associations between crystals and other characteristics of the disease as well as potential risk factors were investigated. Main outcome measures Presence of crystals, fundus signs of MacTel, clinical characteristics, presence of potential risk factors of MacTel. Results Out of 443 probands enrolled in the MacTel study, 203 (46%) had crystalline deposits present; 60% of the cases were bilateral at baseline. Eyes with crystals had a mean letter score of 70.7 (SD=15.9) while those without crystals had a mean of 66.5 letters (SD=15.5, p<0.001). Crystals were present at all stages of the disease and showed high reflectivity within a wide wavelength range. They were located at the anterior surface of the nerve fibre layer, arranged along the nerve fibres, within an annular area centred on the fovea. Significant associations of crystalline deposits were found with a loss of retinal transparency, MPOD loss, fluorescein leakage, retinal thickness and a break in the IS/OS junction line. Associations with environmental risk factors were not found. Conclusions Intraretinal crystals are a frequent phenomenon associated with type 2 MacTel, they may appear at all stages and may aid in the early diagnosis of the disease. Their morphology further implicates Müller cells

  19. The clinical significance of radionuclide bone and gallium scanning in osteomyelitis of the head and neck

    SciTech Connect

    Noyek, A.M.; Kirsh, J.C.; Greyson, N.D.; Wortzman, G.; Jazrawy, H.; Freeman, J.L.; Blair, R.L.; Chapnik, J.S.

    1984-05-01

    Osteomyelitis of the head and neck remains a difficult clinical problem both in diagnosis and treatment evaluation. The purpose of this manuscript is to review our clinical experience with 25 cases of osteomyelitis distributed evenly among the temporal bone and skull base, the paranasal sinuses, and the mandible. Radionuclide bone and gallium scan images accurately depicted the biologic activity of the disease process and permitted accurate treatment evaluation and patient monitoring. This work demonstrates the potentials and limitations of radionuclide imaging with bone and gallium scan agents and attempts to define a role for their contemporary use in the management of osteomyelitis of the head and neck.

  20. 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…

  1. 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

  2. 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. PMID:6499313

  3. 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…

  4. Macular findings on optical coherence tomography in cat-scratch disease neuroretinitis

    PubMed Central

    Habot-Wilner, Z; Zur, D; Goldstein, M; Goldenberg, D; Shulman, S; Kesler, A; Giladi, M; Neudorfer, M

    2011-01-01

    Purpose To describe the macular findings on optical coherence tomography (OCT) in patients with cat-scratch disease (CSD) neuroretinitis. Methods Medical records of all patients diagnosed with CSD neuroretinitis at the Tel Aviv Medical Center between April 2006 and May 2010 were retrospectively reviewed. All patients underwent Stratus OCT macular examination. Results Eight eyes of seven patients with confirmed CSD neuroretinitis, (mean age 33±9.9 years, range 6–48 years) were included in the study. All patients presented clinically with optic nerve swelling and macular edema or macular exudates. OCT demonstrated flattening of the foveal contour, thickening of the neurosensory retina, and accumulation of subretinal fluid (SRF) in all studied eyes. Retinal exudates appeared as multiple hyper-reflective foci in the outer plexiform layer. The average central macular thickness was 460 μm (range 170–906 μm) and the average maximal retinal thickness was 613 μm (range 387–1103 μm), at presentation. The macula appeared normal on repeated exams during follow-up. Conclusion Similar OCT findings were demonstrated in patients with CSD neuroretinitis. SRF was found in all eyes, although was not visible on clinical examination or fluorescein angiography. OCT may be used as an adjunct imaging tool in the diagnosis and follow-up of patients with CSD neuroretinitis. PMID:21660065

  5. Statistical Versus Clinical Significance for Infants with Brain Injury: Reanalysis of Outcome Data from a Randomized Controlled Study

    PubMed Central

    Badr, Lina Kurdahi

    2009-01-01

    By adopting more appropriate statistical methods to appraise data from a previously published randomized controlled trial (RCT), we evaluated the statistical and clinical significance of an intervention on the 18 month neurodevelopmental outcome of infants with suspected brain injury. The intervention group (n =32) received extensive, individualized cognitive/sensorimotor stimulation by public health nurses (PHNs) while the control group (n = 30) received standard follow-up care. At 18 months 43 infants remained in the study (22 = intervention, 21 = control). The results indicate that there was a significant statistical change within groups and a clinical significance whereby more infants in the intervention group improved in mental, motor and neurological functioning at 18 months compared to the control group. The benefits of looking at clinical significance from a meaningful aspect for practitioners are emphasized. PMID:19276403

  6. Persistent Left Superior Vena Cava: A Rare Case with Clinical Significance

    PubMed Central

    Kumar, Raj; Yadav, Sankalp; Verma, Deepak

    2016-01-01

    Persistent Left Superior Vena Cava (PLSVC) is a rare congenital vascular anomaly (incidence of 0.3-0.5% of the general population) which being mostly asymptomatic in its presentation, is usually detected incidentally. There are many practical clinical implications associated with it including arrhythmias. We report a rare case of PLSVC with absent Right Superior Vena Cava (RSVC) (isolated PLSVC), in a 55-year-old lady who had complete heart block followed by sepsis and was diagnosed to have this condition during the permanent cardiac pacemaker implantation and central venous catheter insertion showing an abnormal path of the catheter/pacing leads. The authors also give an insight into its clinical relevance. PMID:27437282

  7. Tests of pancreatic exocrine function - clinical significance in pancreatic and non-pancreatic disorders.

    PubMed

    Keller, Jutta; Aghdassi, Ali Alexander; Lerch, Markus M; Mayerle, Julia V; Layer, Peter

    2009-01-01

    The pancreas functions as the main factory for digestive enzymes and therefore enables food utilisation. Pancreatic exocrine insufficiency, partial or complete loss of digestive enzyme synthesis, occurs primarily in disorders directly affecting pancreatic tissue integrity. However, other disorders of the gastrointestinal tract, such as coeliac disease, inflammatory bowel disease, Zollinger-Ellison syndrome or gastric resection can either mimic or cause pancreatic exocrine insufficiency. The overt clinical symptoms of pancreatic exocrine insufficiency are steatorrhoea and maldigestion, which frequently become apparent in advanced stages. Several direct and indirect function tests are available for assessment of pancreatic function but until today diagnosis of excretory insufficiency is difficult as in mild impairment clinically available function tests show limitations of diagnostic accuracy. This review focuses on diagnosis of pancreatic exocrine insufficiency in pancreatic and non-pancreatic disorders. PMID:19505669

  8. Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections.

    PubMed

    Kahl, Barbara C; Becker, Karsten; Löffler, Bettina

    2016-04-01

    Small colony variants (SCVs) were first described more than 100 years ago for Staphylococcus aureus and various coagulase-negative staphylococci. Two decades ago, an association between chronic staphylococcal infections and the presence of SCVs was observed. Since then, many clinical studies and observations have been published which tie recurrent, persistent staphylococcal infections, including device-associated infections, bone and tissue infections, and airway infections of cystic fibrosis patients, to this special phenotype. By their intracellular lifestyle, SCVs exhibit so-called phenotypic (or functional) resistance beyond the classical resistance mechanisms, and they can often be retrieved from therapy-refractory courses of infection. In this review, the various clinical infections where SCVs can be expected and isolated, diagnostic procedures for optimized species confirmation, and the pathogenesis of SCVs, including defined underlying molecular mechanisms and the phenotype switch phenomenon, are presented. Moreover, relevant animal models and suggested treatment regimens, as well as the requirements for future research areas, are highlighted. PMID:26960941

  9. Clinical significance and new detection system of autoantibodies in myositis with interstitial lung disease.

    PubMed

    Nakashima, R; Hosono, Y; Mimori, T

    2016-07-01

    Anti-aminoacyl-tRNA synthetase (ARS) and anti-melanoma differentiation-associated gene 5 (MDA5) antibodies are closely associated with interstitial lung disease in polymyositis and dermatomyositis. Anti-ARS-positive patients develop common clinical characteristics termed anti-synthetase syndrome and share a common clinical course, in which they respond well to initial treatment with glucocorticoids but in which disease tends to recur when glucocorticoids are tapered. Anti-MDA5 antibody is associated with rapidly progressive interstitial lung disease and poor prognosis, particularly in Asia. Therefore, intensive immunosuppressive therapy is required for anti-MDA5-positive patients from the early phase of the disease. New enzyme-linked immunosorbent assays to detect anti-ARS and anti-MDA5 antibodies have recently been established and are suggested to be efficient and useful. These assays are expected to be widely applied in daily practice. PMID:27252271

  10. 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

  11. 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

  12. Electrocardiographic right and left bundle branch block patterns in athletes: prevalence, pathology, and clinical significance.

    PubMed

    Kim, Jonathan H; Baggish, Aaron L

    2015-01-01

    Differentiating benign electrocardiographic (ECG) patterns in athletes from those representative of underlying cardiac pathology is both clinically relevant and challenging. Complete right (RBBB) and left (LBBB) bundle branch block are relatively rare in asymptomatic athletic populations, and current expert consensus guidelines recommend further clinical investigation upon detection of either ECG pattern. However, present data suggest that typical RBBB is not associated with structural cardiac pathology and may alternatively represent an ECG marker of exercise-induced right ventricular remodeling. In accordance with current guidelines, the presence of asymptomatic LBBB in athletes is not associated with normal exercise physiology and more likely indicative of underlying cardiac pathology. While long-term outcomes for asymptomatic athletes with RBBB or LBBB remain unknown, current evidence regarding these ECG patterns should be considered to improve the specificity of future athlete-specific ECG interpretation guidelines. PMID:25836379

  13. Biologic and clinical significance of molecular profiling in Chronic Lymphocytic Leukemia

    PubMed Central

    Tom, Butler; Gribben, J.G.

    2010-01-01

    CLL is extremely heterogeneous in its clinical course, with some patients living decades with no need for treatment whilst others have a rapidly aggressive clinical course. A major focus of research has been to try to identify those biological factors that influence this heterogeneity. The goal of therapy has been to maintain the best quality of life and treat only when patients become symptomatic from their disease. For the majority of patients this means following a “watch and wait” approach to determine the rate of progression of the disease and assess for development of symptoms. Any alteration to this approach will require identification of criteria that define patients sufficiently “high-risk” that they gain benefit by introduction of early therapy. The use of molecular profiling to suggest particular therapies is currently appropriate only in defining the treatment of the minority of patients with 17p deletions or p53 mutations and in all other circumstances remains a clinical trial question. PMID:20398985

  14. The significance of clinical practice guidelines on adult varicocele detection and management

    PubMed Central

    Shridharani, Anand; Owen, Ryan C; Elkelany, Osama O; Kim, Edward D

    2016-01-01

    Varicoceles are the most common correctable etiology of male factor infertility. However, the detection and management of varicoceles have not been standardized. This has led to decades of debate regarding the effect of varicocele on male infertility and subsequently whether repair leads to an improved fertility status. The current body of evidence investigating the role of varicocele and varicocelectomy is weak and conflicting. The stance taken by the AUA and ASRM suggests that there is insufficient outcomes data to support evidenced-based guidelines, citing evidence used to provide current recommendations are generally of a low quality level. On the other hand, the EAU Guidelines give a level 1a of evidence for management of varicoceles that are clinically palpable, associated with subnormal semen analyses and having otherwise unexplained fertility. Besides aiding with clinical varicocele detection and management, clinical practice opinion statements and guidelines aim to direct and strengthen the infrastructure of future studies. We review the current status of opinion statements and guidelines in varicocele and management detection with focus on their application in practice. PMID:26806081

  15. Peripheral neuropathy associated with monoclonal IgG of undetermined significance: clinical, electrophysiologic, pathologic and therapeutic study of 14 cases.

    PubMed

    Hermosilla, E; Lagueny, A; Vital, C; Vital, A; Ferrer, X; Steck, A; Julien, J

    1996-01-01

    Fourteen patients with peripheral neuropathy and monoclonal IgG of undetermined significance are reported with a retrospective study of the clinical features, electrophysiologic and sural nerve biopsy findings. There were two groups. Five patients had a relapsing chronic sensorimotor polyneuropathy with clinical (5/5), electrophysiologic (4/5) and pathologic (5/5) features compatible with chronic inflammatory demyelinating polyneuropathies (CIDP). The nine others had a slowly progressive sensory (5/9) (SPNP) or sensorimotor (4/9) (SMPNP) axonal polyneuropathy. Four patients of the first group were treated with intravenous human immunoglobulin (400 mg/kg/day for five days) with significant clinical improvement. The motor conduction velocities and distal latencies of two of these patients improved following treatment, thus matching the clinical improvement. Our results on peripheral nerve biopsies confirm the differentiation of patients with CIDP from those with SMPNP and SPNP. There was no specific immunologic serologic reactivity in any of the cases. PMID:10975722

  16. Comparative Safety and Tolerability of Anti-VEGF therapy in Age-Related Macular Degeneration

    PubMed Central

    Modi, Yasha S.; Tanchon, Carley; Ehlers, Justis P

    2015-01-01

    Neovascular age-related macular degeneration (NVAMD) is one of the leading causes of blindness. Over the last decade, the treatment of NVAMD has been revolutionized by the development intravitreal anti-vascular endothelial growth factor (VEGF) therapies. Several anti-VEGF medications are used for the treatment of NVAMD. The safety and tolerability of these medications deserve review given the high prevalence of NVAMD and the significant utilization of these medications. Numerous large randomized clinical trials have not shown any definitive differential safety relative to ocular or systemic safety of these medications. Intravitreal anti-VEGF therapy does appear to impact systemic VEGF levels, but the implications of these changes remain unclear. One unique safety concern relates drug compounding and the potential risks of contamination, specifically for bevacizumab. Continued surveillance for systemic safety concerns, particularly for rare events is merited. Overall these medications are well tolerated and effective in the treatment of NVAMD. PMID:25700714

  17. MACULAR COLOBOMA IN A CHILD WITH USHER SYNDROME.

    PubMed

    Ishaq, Mazhar; Mukhtar, Ahsan; Khan, Saim

    2015-01-01

    Macular coloboma is a rare entity and its concomitance with Usher syndrome is described here. A 14 years male child was studied in detail along with other family members. He underwent two complete ophthalmologic examinations (4-years follow-up), including visual assessment, orthoptic evaluation, colour vision test, visual fields, corneal topography, Optical coherence tomography, fluorescein angiography, and electroretinography. Detailed ophthalmic examination was also conducted on other asymptomatic members of the same family. Patient had sensorineural deafness, poor visual acuity, and progressive visual field impairment in both eyes, bilaterally presenting macular coloboma and atypical retinitis pigmentosa pattern. The other investigated relatives did not show any specific and/or significant ocular disorder. This concurrence represents no genetic pattern and is observed in sporadic cases. PMID:26411142

  18. Classification, Identification, and Clinical Significance of Haemophilus and Aggregatibacter Species with Host Specificity for Humans

    PubMed Central

    2014-01-01

    SUMMARY The aim of this review is to provide a comprehensive update on the current classification and identification of Haemophilus and Aggregatibacter species with exclusive or predominant host specificity for humans. Haemophilus influenzae and some of the other Haemophilus species are commonly encountered in the clinical microbiology laboratory and demonstrate a wide range of pathogenicity, from life-threatening invasive disease to respiratory infections to a nonpathogenic, commensal lifestyle. New species of Haemophilus have been described (Haemophilus pittmaniae and Haemophilus sputorum), and the new genus Aggregatibacter was created to accommodate some former Haemophilus and Actinobacillus species (Aggregatibacter aphrophilus, Aggregatibacter segnis, and Aggregatibacter actinomycetemcomitans). Aggregatibacter species are now a dominant etiology of infective endocarditis caused by fastidious organisms (HACEK endocarditis), and A. aphrophilus has emerged as an important cause of brain abscesses. Correct identification of Haemophilus and Aggregatibacter species based on phenotypic characterization can be challenging. It has become clear that 15 to 20% of presumptive H. influenzae isolates from the respiratory tracts of healthy individuals do not belong to this species but represent nonhemolytic variants of Haemophilus haemolyticus. Due to the limited pathogenicity of H. haemolyticus, the proportion of misidentified strains may be lower in clinical samples, but even among invasive strains, a misidentification rate of 0.5 to 2% can be found. Several methods have been investigated for differentiation of H. influenzae from its less pathogenic relatives, but a simple method for reliable discrimination is not available. With the implementation of identification by matrix-assisted laser desorption ionization–time of flight mass spectrometry, the more rarely encountered species of Haemophilus and Aggregatibacter will increasingly be identified in clinical microbiology

  19. Comparison of intravitreal bevacizumab with macular photocoagulation for treatment of diabetic macular edema: a systemic review and Meta-analysis

    PubMed Central

    Liu, Xiang-Dong; Zhou, Xiao-Dong; Wang, Zhi; Shen, Hong-Jie

    2014-01-01

    AIM To further evaluate the efficacy and safety of intravitreal bevacizumab (IVB) versus macular photocoagulation (MPC) in treatment of diabetic macular edema (DME) by Meta-analysis. METHODS Pertinent publications were identified through systemic searches of PubMed, Medline, EMBASE, and the Cochrane Controlled Trials Register up to 30 November, 2013. Changes in central macular thickness (CMT) in µm and best-corrected visual acuity (BCVA) in logMAR equivalents were extracted at 1, 3, 6, 12 and 24mo after initial treatment, and a Meta-analysis was carried out to compare results between groups receiving IVB and MPC. RESULTS Five randomized controlled trial (RCTs) and one high-quality comparative study were identified and included. Our Meta-analysis revealed that both IVB and MPC resulted in the improvements of CMT and BCVA in eyes with DME at 1mo after initial treatment, with IVB being significantly superior to MPC (P=0.01 and 0.02, respectively). The improvements of both measure outcomes at 3, 6, 12 and 24mo after treatment did not vary significantly between the IVB groups and MPC groups (CMT at 3mo, P=0.85; at 6mo, P=0.29; at 12mo, P=0.56; at 24mo, P=0.71; BCVA at 3mo, P=0.31; at 6mo, P= 0.30; at 12mo, P=0.23; at 24mo, P=0.52). However, the number of observed adverse events was low in all studies. CONCLUSION Current evidence shows IVB treatment trends to be more effective in improvements of macular edema and vision in eyes with DME at an earlier follow up (1mo) compared with MPC. At other time, both interventions have comparable efficacy without statistical significances. PMID:25540764

  20. Predicting visual outcomes for macular disease using optical coherence tomography

    PubMed Central

    Keane, Pearse A.; Sadda, Srinivas R.

    2011-01-01

    In recent years, the management of macular disease has undergone radical changes, in part because of new therapeutic approaches, but also due to the introduction of a new imaging modality – optical coherence tomography (OCT). The application of OCT imaging has clarified many aspects of chorioretinal disease pathophysiology and elucidated many hitherto unrecognized disease characteristics. From an early stage in its development, OCT has also been revolutionary in attempting to extract clinically useful measurements from image data in an automated fashion. As a result, OCT-derived measurements of retinal thickness have been rapidly embraced in clinical and research settings. However, as knowledge of OCT image analysis has developed, it has become increasingly clear that even accurate measurements of retinal thickness may fail to predict visual outcomes for many diseases. As a result, the focus of much current clinical imaging research is on the identification of other OCT-derived anatomic biomarkers predictive of visual outcomes – such biomarkers could serve as surrogate endpoints in clinical trials and provide prognostic information in clinical practice. In this review, we begin by highlighting the importance of accurate visual function assessment and describing the fundamentals of OCT image evaluation, before describing the current state-of-the-art with regard to predicting visual outcomes, for a variety of macular diseases, using OCT. PMID:23960916

  1. Clinical significance of brain phenylalanine concentration assessed by in vivo proton magnetic resonance spectroscopy in phenylketonuria.

    PubMed

    Leuzzi, V; Bianchi, M C; Tosetti, M; Carducci, C L; Carducci, C A; Antonozzi, I

    2000-09-01

    Recent studies using in vivo proton magnetic resonance spectroscopy (1H MRS) have suggested that plasma phenylalanine (Phe) may not be a reliable indicator of brain Phe level in subjects with phenylketonuria (PKU). Interindividual variation in cerebral Phe can contribute to the phenotypic variability of the disease. We report the results of the direct assessment of brain Phe by 1H MRS in 10 off-diet PKU patients (aged 15.5-30.5 years), 4 detected and treated early, 6 late. In a single patient, brain Phe was evaluated before and 15 days after diet discontinuation. FLAIR MRI and 1H MRS were performed in the same setting by a 1.5 T clinical MR scanner. MR images were scored according to the extent of the lobar white-matter hyperintensity. Brain 1H MRS Phe signal (resonating at 7.36 ppm) was evaluated as a ratio to the creatine+phosphocreatine signal. Brain Phe was correlated with clinical, biochemical and MRI findings. Results were as follows. (1) An abnormal concentration of brain Phe was detected in all 10 PKU subjects (ranging from 0.030 to 0.074), associated with a wide interindividual variability of concurrent plasma Phe (ranging from 724 to 2800 micromol/L). (2) In late-detected subjects, brain Phe concentration correlated with clinical phenotype better than did plasma Phe. The discrepancy between brain and plasma Phe was relevant from a clinical point of view in two cases: in one, a late-detected patient with normal mental development, a high level of plasma Phe was associated with a relatively low concentration of brain Phe; in the other, a late-detected subject with severe neurological impairment, a very high level of brain Phe was associated with plasma Phe compatible with the diagnosis of mild PKU. (3) White-matter alterations were detected in all patients. FLAIR MRI sequences disclosed an involvement of optic chiasma and tracts in 7 subjects. No correlation was found between white-matter alterations and concurrent brain Phe concentrations. (4) In the only

  2. [Age-related macular degeneration].

    PubMed

    Garcia Layana, A

    1998-01-01

    Age-related macular degeneration (ARMD) is the leading cause of blindness in the occidental world. Patients suffering this process have an important reduction on their quality of life being handicapped to read, to write, to recognise faces of their friends, or even to watch the television. One of the main problems of that disease is the absence of an effective treatment able to revert the process. Laser treatment is only useful in a limited number of patients, and even in these cases recurrent lesions are frequent. These facts and the progressive ageing of our society establish the ARMD as one of the biggest aim of medical investigations for the next century, and currently is focus of attention in the most industrialised countries. One of the most promising pieces of research is focused in the investigation of the risk factors associated with the age-related macular degeneration, in order to achieve a prophylactic treatment avoiding its appearance. Diet elements such as fat ingestion or reduced antioxidant intakes are being investigated as some of these factors, what open a new possibility for a prophylactic treatment. Finally, research is looking for new therapeutic modalities such as selective radiotherapy in order to improve or maintain the vision of these patients. PMID:10420956

  3. The clinical significance of classical and new emerging determinants of adenomyosis

    PubMed Central

    Bodur, Serkan; Dundar, Ozgur; Pektas, Mine Kanat; Babayigit, Mustafa Alparslan; Ozden, Okan; Kucukodacı, Zafer

    2015-01-01

    Objective: The present study aims to analyze the diagnostic accuracy of clinical characteristics together with new emerging laboratory markers of adenomyosis. Methods: This study was a retrospective analysis of clinical and laboratory characteristics of 99 women who underwent hysterectomies with (study group) or without (control group) a diagnosis of adenomyosis, 56 and 43 patients in each group, respectively. Results: The women with adenomyosis were more likely to have younger age (OR = 1.14, 0.789-0.971 95% CI, P = 0.010), higher parity (OR = 1.81, 0.308-0.988 95% CI, P = 0.046), higher number of curettage (OR = 1.90, 1.189-3.041 95% CI, P = 0.007), dysmenorrhea (OR = 117.49, 2.715-5084.883 95% CI, P = 0.013) and elevated mean platelet volume (OR = 5.17, 2.054-13.028 95% CI, P = 0.000). After receiver-operating-characteristics curve analysis, using a cut-point of 8.5 fL, the preoperative mean platelet volume predicted adenomyosis with a sensitivity of 56.6% and specificity of 82.6%. Conclusions: Those findings suggest gynecologists to give priority on adenomyosis when premenopausal paraous patient with a history of curettages admitted with a complaint of dysmenorrhea and elevated levels of MPV. PMID:26221354

  4. Incidence and Clinical Significance of De Novo Donor Specific Antibodies after Kidney Transplantation

    PubMed Central

    Panagiotellis, Konstantinos; Iniotaki, Aliki; Boletis, John N.

    2013-01-01

    Kidney transplantation has evolved over more than half a century and remarkable progress has been made in patient and graft outcomes. Despite these advances, chronic allograft dysfunction remains a major problem. Among other reasons, de novo formation of antibodies against donor human leukocyte antigens has been recognized as one of the major risk factors for reduced allograft survival. The type of treatment in the presence of donor specific antibodies (DSA) posttransplantation is largely related to the clinical syndrome the patient presents with at the time of detection. There is no consensus regarding the treatment of stable renal transplant recipients with circulating de novo DSA. On the contrast, in acute or chronic allograft dysfunction transplant centers use various protocols in order to reduce the amount of circulating DSA and achieve long-term graft survival. These protocols include removal of the antibodies by plasmapheresis, intravenous administration of immunoglobulin, or depletion of B cells with anti-CD20 monoclonal antibodies along with tacrolimus and mycophenolate mofetil. This review aims at the comprehension of the clinical correlations of de novo DSA in kidney transplant recipients, assessment of their prognostic value, and providing insights into the management of these patients. PMID:24348683

  5. Clinical significance of de Garengeot's hernia: A case of acute appendicitis and review of the literature

    PubMed Central

    Piperos, Theodoros; Kalles, Vasileios; Al Ahwal, Yousef; Konstantinou, Evangelos; Skarpas, George; Mariolis-Sapsakos, Theodoros

    2011-01-01

    Introduction The presence of the appendix in a femoral hernia sac is known as de Garengeot's hernia. We report a rare case of an elderly woman with femoral hernia appendicitis and discuss the surgical pitfalls and considerations through a literature review. Presentation of case An 83-year-old woman presented with fever and right lower quadrant abdominal pain. Clinical examination revealed a femoral hernia. Ultrasonography confirmed bowel was present in the hernia sac. In the operation room, an acutely inflamed appendix was recognized within the sac. The patient underwent appendectomy and hernia repair with sutures. Discussion Acute appendicitis within a femoral hernia is rare and multiple dilemmas exist regarding its treatment. An incision below the inguinal ligament is a reasonable choice in order to access the hernia sac. A mesh should be placed in non-infectious appendectomy while herniorrhaphy is preferred in cases of appendicitis. Conclusion The presence of the vermiform appendix in a femoral hernia sac is rare but the surgeon should be aware of this clinical entity. Prompt diagnosis and appropriate surgical treatment is the key to avoid complications. PMID:22288062

  6. Clinical significance of microRNAs in chronic and acute human leukemia.

    PubMed

    Yeh, Chien-Hung; Moles, Ramona; Nicot, Christophe

    2016-01-01

    Small non-coding microRNAs (miRNAs) are epigenetic regulators that target specific cellular mRNA to modulate gene expression patterns and cellular signaling pathways. miRNAs are involved in a wide range of biological processes and are frequently deregulated in human cancers. Numerous miRNAs promote tumorigenesis and cancer progression by enhancing tumor growth, angiogenesis, invasion and immune evasion, while others have tumor suppressive effects (Hayes, et al., Trends Mol Med 20(8): 460-9, 2014; Stahlhut and Slack, Genome Med 5 (12): 111, 2013). The expression profile of cancer miRNAs can be used to predict patient prognosis and clinical response to treatment (Bouchie, Nat Biotechnol 31(7): 577, 2013). The majority of miRNAs are intracellular localized, however circulating miRNAs have been detected in various body fluids and represent new biomarkers of solid and hematologic cancers (Fabris and Calin, Mol Oncol 10(3):503-8, 2016; Allegra, et al., Int J Oncol 41(6): 1897-912, 2012). This review describes the clinical relevance of miRNAs, lncRNAs and snoRNAs in the diagnosis, prognosis and treatment response in patients with chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML) and acute adult T-cell leukemia (ATL). PMID:27179712

  7. Clinical significance of the isolation of Candida species from hospitalized patients

    PubMed Central

    Magalhães, Yankee C.; Bomfim, Maria Rosa Q.; Melônio, Luciane C.; Ribeiro, Patrícia C.S.; Cosme, Lécia M.; Rhoden, Cristianne R.; Marques, Sirlei G.

    2015-01-01

    In this study, we isolated and phenotypically identified 108 yeast strains from various clinical specimens collected from 100 hospitalized patients at three tertiary hospitals in São Luís-Maranhão, Brazil, from July to December 2010. The isolates were analyzed for their susceptibility to four of the most widely used antifungal agents in the surveyed hospitals, amphotericin B, fluconazole, 5-flucytosine and voriconazole. The species identified were Candida albicans (41.4%), Candida tropicalis (30.1%), C. glabrata (7.4%), Candida parapsilosis (5.5%), Candida krusei (4.6%), Cryptococcus neoformans (4.6%), Trichosporon spp . (3.7%), Candida norvegensis (0.9%), Rhodotorula glutinis (0.9%) and Pichia farinosa (0.9%). A higher isolation rate was observed in the following clinical specimens: urine (54 isolates; 50%), respiratory tract samples (21 isolates; 19.4%) and blood (20 isolates; 18.6%). Candida albicans isolates were 100% sensitive to all antifungal agents tested, whereas Candida krusei and Crytococcus neoformans displayed intermediate resistance to 5-flucytosine, with Minimal Inhibitory Concentration (MIC) values of 8 mg/mL and 16 mg/mL, respectively. Both strains were also S-DD to fluconazole with an MIC of 16 mg/mL. C. tropicalis was resistant to 5-flucytosine with an MIC of 32 μg/mL. This study demonstrates the importance of identifying the yeast species involved in community and nosocomial infections. PMID:26221096

  8. Clinical significance of the isolation of Candida species from hospitalized patients.

    PubMed

    Magalhães, Yankee C; Bomfim, Maria Rosa Q; Melônio, Luciane C; Ribeiro, Patrícia C S; Cosme, Lécia M; Rhoden, Cristianne R; Marques, Sirlei G

    2015-03-01

    In this study, we isolated and phenotypically identified 108 yeast strains from various clinical specimens collected from 100 hospitalized patients at three tertiary hospitals in São Luís-Maranhão, Brazil, from July to December 2010. The isolates were analyzed for their susceptibility to four of the most widely used antifungal agents in the surveyed hospitals, amphotericin B, fluconazole, 5-flucytosine and voriconazole. The species identified were Candida albicans (41.4%), Candida tropicalis (30.1%), C. glabrata (7.4%), Candida parapsilosis (5.5%), Candida krusei (4.6%), Cryptococcus neoformans (4.6%), Trichosporon spp . (3.7%), Candida norvegensis (0.9%), Rhodotorula glutinis (0.9%) and Pichia farinosa (0.9%). A higher isolation rate was observed in the following clinical specimens: urine (54 isolates; 50%), respiratory tract samples (21 isolates; 19.4%) and blood (20 isolates; 18.6%). Candida albicans isolates were 100% sensitive to all antifungal agents tested, whereas Candida krusei and Crytococcus neoformans displayed intermediate resistance to 5-flucytosine, with Minimal Inhibitory Concentration (MIC) values of 8 mg/mL and 16 mg/mL, respectively. Both strains were also S-DD to fluconazole with an MIC of 16 mg/mL. C. tropicalis was resistant to 5-flucytosine with an MIC of 32 μg/mL. This study demonstrates the importance of identifying the yeast species involved in community and nosocomial infections. PMID:26221096

  9. Immunological and clinical significance of HLA class I antigen processing machinery component defects in malignant cells.

    PubMed

    Concha-Benavente, Fernando; Srivastava, Raghvendra; Ferrone, Soldano; Ferris, Robert L

    2016-07-01

    Experimental as well as clinical studies demonstrate that the immune system plays a major role in controlling generation and progression of tumors. The cancer immunoediting theory supports the notion that tumor cell immunogenicity is dynamically shaped by the immune system, as it eliminates immunogenic tumor cells in the early stage of the disease and then edits their antigenicity. The end result is the generation of a tumor cell population able to escape from immune recognition and elimination by tumor infiltrating lymphocytes. Two major mechanisms, which affect the target cells and the effector phase of the immune response, play a crucial role in the editing process. One is represented by the downregulation of tumor antigen (TA) processing and presentation because of abnormalities in the HLA class I antigen processing machinery (APM). The other one is represented by the anergy of effector immune infiltrates in the tumor microenvironment caused by aberrant inhibitory signals triggered by immune checkpoint receptor (ICR) ligands, such as programmed death ligand-1 (PD-L1). In this review, we will focus on tumor immune escape mechanisms caused by defects in HLA class I APM component expression and/or function in different types of cancer, with emphasis on head and neck cancer (HNC). We will also discuss the immunological implications and clinical relevance of these HLA class I APM abnormalities. Finally, we will describe strategies to counteract defective TA presentation with the expectation that they will enhance tumor recognition and elimination by tumor infiltrating effector T cells. PMID:27264839

  10. Iron deficiency anemia presenting with macular star.

    PubMed

    Trivedi, Bhakti P; Ravindran, Meenakshi; Pawar, Neelam; Ramakrishnan, Rengappa; Shelke, Vijaysai

    2015-10-01

    We report the case of 16-year-old girl who presented with sudden painless decreased vision in her right eye of 5 days' duration. Anterior segment examination in both eyes showed conjunctival pallor. Results of ophthalmoscopic examination and optical coherence tomography were consistent with macular preretinal hemorrhage in both eyes with macular star in the left eye. Hematologic investigation disclosed severe iron deficiency anaemia. After 2 months, with oral substitution therapy with ferrous ascorbate and improved iron levels, the patient's visual acuity improved and macular preretinal hemorrhage resolved in both eyes. PMID:26486041

  11. 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

  12. 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

  13. Clinically Significant Fatigue: Prevalence and Associated Factors in an International Sample of Adults with Multiple Sclerosis Recruited via the Internet

    PubMed Central

    Weiland, Tracey J.; Jelinek, George A.; Marck, Claudia H.; Hadgkiss, Emily J.; van der Meer, Dania M.; Pereira, Naresh G.; Taylor, Keryn L.

    2015-01-01

    Background Fatigue contributes a significant burden of disease for people with multiple sclerosis (PwMS). Modifiable lifestyle factors have been recognized as having a role in a range of morbidity outcomes in PwMS. There is significant potential to prevent and treat fatigue in PwMS by addressing modifiable risk factors. Objectives To explore the associations between clinically significant fatigue and demographic factors, clinical factors (health-related quality of life, disability and relapse rate) and modifiable lifestyle, disease-modifying drugs (DMD) and supplement use in a large international sample of PwMS. Methods PwMS were recruited to the study via Web 2.0 platforms and completed a comprehensive survey measuring demographic, lifestyle and clinical characteristics, including health-related quality of life, disability, and relapse rate. Results Of 2469 participants with confirmed MS, 2138 (86.6%) completed a validated measure of clinically significant fatigue, the Fatigue Severity Scale. Participants were predominantly female from English speaking countries, with relatively high levels of education, and due to recruitment methods may have been highly pro-active about engaging in lifestyle management and self-help. Approximately two thirds of our sample (1402/2138; 65.6% (95% CI 63.7–67.7)) screened positive for clinically significant fatigue. Bivariate associations were present between clinically significant fatigue and several demographic, clinical, lifestyle, and medication variables. After controlling for level of disability and a range of stable socio-demographic variables, we found increased odds of fatigue associated with obesity, DMD use, poor diet, and reduced odds of fatigue with exercise, fish consumption, moderate alcohol use, and supplementation with vitamin D and flaxseed oil. Conclusion This study supports strong and significant associations between clinically significant fatigue and modifiable lifestyle factors. Longitudinal follow-up of this

  14. Cutaneous vasculitis in primary Sjögren syndrome: classification and clinical significance of 52 patients.

    PubMed

    Ramos-Casals, Manuel; Anaya, Juan-Manuel; García-Carrasco, Mario; Rosas, José; Bové, Albert; Claver, Gisela; Diaz, Luis-Aurelio; Herrero, Carmen; Font, Josep

    2004-03-01

    To analyze the different clinical and histologic types of cutaneous vasculitis in patients with primary Sjögren syndrome (SS), we investigated the clinical and immunologic characteristics of 558 consecutive patients with primary SS from our units and selected those with clinical evidence of cutaneous lesions, excluding drug reactions and xeroderma. All patients fulfilled 4 or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. A total of 89 (16%) patients presented with cutaneous involvement (88 female patients and 1 male; mean age, 51.8 yr). The main cutaneous involvement was cutaneous vasculitis, present in 52 (58%) patients. There were 51 (98%) female patients and 1 (2%) male, with a mean age at diagnosis of cutaneous vasculitis of 51 years (range, 20-80 yr). Fourteen presented with cryoglobulinemic vasculitis, 11 with urticarial vasculitis, and the remaining 26, with cutaneous purpura not associated with cryoglobulins. A skin biopsy specimen was obtained in 38 patients (73%). Involvement of small-sized vessels was observed in 36 (95%) patients (leukocytoclastic vasculitis), while the remaining 2 (5%) presented with medium-sized vessel vasculitis (necrotizing vasculitis). Patients with cutaneous vasculitis had a higher prevalence of articular involvement (50% vs 29%, p = 0.044), peripheral neuropathy (31% vs 4%, p < 0.001), Raynaud phenomenon (40% vs 15%, p = 0.008), renal involvement (10% vs 0%, p = 0.028), antinuclear antibodies (88% vs 60%, p = 0.002), rheumatoid factor (78% vs 48%, p = 0.004), anti-Ro/SS-A antibodies (70% vs 43%, p = 0.011), and hospitalization (25% vs 4%, p = 0.005) compared with SS patients without vasculitis. Six (12%) patients died, all of whom had multisystemic cryoglobulinemia.In conclusion, cutaneous involvement was detected in 16% of patients with primary SS, with cutaneous vasculitis being the most frequent process. The main characteristics of SS-associated cutaneous vasculitis were the

  15. Clinical Significance of the Glasgow Prognostic Score for Survival after Colorectal Cancer Surgery.

    PubMed

    Eren, Tunc; Burcu, Busra; Tombalak, Ercument; Ozdemir, Tugrul; Leblebici, Metin; Ozemir, Ibrahim Ali; Ziyade, Sedat; Alimoglu, Orhan

    2016-06-01

    Glasgow prognostic score (GPS) has been found to be a useful tool in various cancer types. Our aim was to evaluate the significance of GPS in patients operated on for colorectal cancer (CRC). Patients with CRC who underwent radical resections between April 2010 and January 2015 were retrospectively evaluated. GPS was estimated based on the preoperative measurement of C-reactive protein and serum albumin levels. Data including demographics, laboratory and pathological parameters, surgical outcomes, and late-term follow-up results were analyzed. The study group of 115 patients consisted of 51 (44 %) women and 64 (56 %) men with a median age of 66 (range 32-91) years. The mean follow-up period was 20 (range 7-41) months. Tumor size and wound infection rates were significantly increased in patients with higher GPS (p = 0.019 and p = 0.003, respectively). According to multivariate analyses, CEA and GPS were found to be independent risk factors significantly effecting mortality (p = 0.001 and p = 0.009, respectively). At the end of the late-term follow-up period, it was detected that cancer-specific survival significantly decreased as the GPS increased (p = 0.016). The GPS is a significant prognostic factor in CRC and should be included in the routine preoperative assessment of all surgically treated CRC patients. PMID:26925798

  16. Genetic and Chromosomal Aberrations and Their Clinical Significance in Renal Neoplasms

    PubMed Central

    Yap, Ning Yi; Rajandram, Retnagowri; Ng, Keng Lim; Pailoor, Jayalakshmi; Fadzli, Ahmad; Gobe, Glenda Carolyn

    2015-01-01

    The most common form of malignant renal neoplasms is renal cell carcinoma (RCC), which is classified into several different subtypes based on the histomorphological features. However, overlaps in these characteristics may present difficulties in the accurate diagnosis of these subtypes, which have different clinical outcomes. Genomic and molecular studies have revealed unique genetic aberrations in each subtype. Knowledge of these genetic changes in hereditary and sporadic renal neoplasms has given an insight into the various proteins and signalling pathways involved in tumour formation and progression. In this review, the genetic aberrations characteristic to each renal neoplasm subtype are evaluated along with the associated protein products and affected pathways. The potential applications of these genetic aberrations and proteins as diagnostic tools, prognostic markers, or therapeutic targets are also assessed. PMID:26448938

  17. [Expression and Clinical Significance of Lymphoid Enhancer-Binding Factor 1 in Acute Leukemias].

    PubMed

    Huo, Wan-Ying; Gao, Ju

    2015-06-01

    Lymphoid enhancer-binding factor 1 (LEF1), a key downstream effector of Wnt/β-catenin signal transduction pathway, plays a crucial role in the maintenance, proliferation and differentiation of normal hematopoietic stem/progenitor cells through regulating the transcription of its target genes. Aberrant LEF1 expression has been documented in a variety of leukemias, and implicated in the prediction of prognosis. Nevertheless, discrepancies exist regarding the expression level and clinical implication of LEF1 in different