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Sample records for diseases radiologic-pathologic correlation

  1. Spinal Metastases of Extramammary Paget Disease with Radiologic-Pathologic Correlation.

    PubMed

    Little, Jason T; Lehman, Vance T; Morris, Jonathan M; Lehman, Julia S; Diehn, Felix E

    2016-05-01

    Extramammary Paget disease (EMPD) is an uncommon malignancy. It manifests either in the primary form in the skin as an intraepithelial neoplasm, or in secondary form as pagetoid (intraepithelial) spread of an underlying internal carcinoma to the skin. Although local invasion and recurrence of primary extramammary Paget disease are relatively frequent, widespread metastases are rare. As such, there are very few reports and little characterization of the radiologic features of widespread spinal metastases. To our knowledge, there are no prior reports of a metastatic extramammary Paget disease presenting as a painful pathologic vertebral body compression fracture. We report the radiological features of a case of primary extramammary Paget disease with subsequent spinal metastases presenting as a painful compression fracture.

  2. The infected liver: radiologic-pathologic correlation.

    PubMed

    Mortelé, Koenraad J; Segatto, Enrica; Ros, Pablo R

    2004-01-01

    Recent technologic advances have significantly enhanced the role of imaging in the detection, characterization, and management of infectious diseases involving the liver. In addition, imaging-guided percutaneous drainage has greatly improved the clinical treatment of patients with focal liver abscess. Infectious liver diseases can be accurately evaluated with ultrasonography (US), computed tomography (CT), and magnetic resonance (MR) imaging. Characteristic changes in US echogenicity, CT attenuation, or MR imaging signal intensity and typical enhancement patterns can contribute to the diagnosis of specific infectious diseases, including abscesses, parasitic diseases, fungal diseases, granulomatous diseases, viral hepatitis, and other less common infections. CT is particularly helpful in revealing the presence of calcifications and gas and in detailing the enhancement pattern. The multiplanar capability of MR imaging and its sensitivity to small differences in tissue composition increase its specificity for certain hepatic infections, including hydatid cyst and candidiasis. Radiologic findings may be sufficient to obviate aspiration or histologic examination, although in most instances they are less specific. Nevertheless, imaging findings taken together with appropriate clinical information may provide the most likely diagnosis, even if biopsy is sometimes required for confirmation.

  3. Percutaneous transluminal angioplasty: radiological-pathological correlation

    SciTech Connect

    Saffitz, J.E.; Totty, W.G.; McClennan, B.L.; Gilula, L.A.

    1981-12-01

    Radiological and pathological assessment of the degree and extent of arterial injury caused by balloon angioplasty was performed in 20 renal arteries obtained at autopsy. Intact arteries were studied angiographically before and after dilatation and then examined histologically. Both normal and diseased arteries were subjected to varying degrees of dilatation. Damage ranged from minimal inimal disruption to major tears of the muscular media. Equivalent dilatory force created greater damage in the distal (muscular) than in the proximal (elastic) portion of the renal artery. There was no evidence of plaque remodling or compression.

  4. From the radiologic pathology archives imaging of osteonecrosis: radiologic-pathologic correlation.

    PubMed

    Murphey, Mark D; Foreman, Kristopher L; Klassen-Fischer, Mary K; Fox, Michael G; Chung, Ellen M; Kransdorf, Mark J

    2014-01-01

    Osteonecrosis is common and represents loss of blood supply to a region of bone. Common sites affected include the femoral head, humeral head, knee, femoral/tibial metadiaphysis, scaphoid, lunate, and talus. Symptomatic femoral head osteonecrosis accounts for 10,000-20,000 new cases annually in the United States. In contradistinction, metadiaphyseal osteonecrosis is often occult and asymptomatic. There are numerous causes of osteonecrosis most commonly related to trauma, corticosteroids, and idiopathic. Imaging of osteonecrosis is frequently diagnostic with a serpentine rim of sclerosis on radiographs, photopenia in early disease at bone scintigraphy, and maintained yellow marrow at MR imaging with a serpentine rim of high signal intensity (double-line sign) on images obtained with long repetition time sequences. These radiologic features correspond to the underlying pathology of osseous response to wall off the osteonecrotic process and attempts at repair with vascularized granulation tissue at the reactive interface. The long-term clinical importance of epiphyseal osteonecrosis is almost exclusively based on the likelihood of overlying articular collapse. MR imaging is generally considered the most sensitive and specific imaging modality both for early diagnosis and identifying features that increase the possibility of this complication. Treatment subsequent to articular collapse and development of secondary osteoarthritis typically requires reconstructive surgery. Malignant transformation of osteonecrosis is rare and almost exclusively associated with metadiaphyseal lesions. Imaging features of this dire sequela include aggressive bone destruction about the lesion margin, cortical involvement, and an associated soft-tissue mass. Recognizing the appearance of osteonecrosis, which reflects the underlying pathology, improves radiologic assessment and is important to guide optimal patient management.

  5. A history of radiologic pathology correlation at the Armed Forces Institute of Pathology and its evolution into the American Institute for Radiologic Pathology.

    PubMed

    Murphey, Mark D; Madewell, John E; Olmsted, William W; Ros, Pablo R; Neiman, Harvey L

    2012-02-01

    The evolution of the Armed Forces Institute of Pathology (AFIP) has played an important role in the history of pathology education and in radiologic pathology correlation in the United States. From its humble beginnings as a museum, showcasing dried and varnished morbid specimens--human relics of the Civil War, the institute became a leader in pathology. Later, it became a center of instruction for radiology residents seeking to understand the pathologic findings that underlay the radiologic appearance of disease. Images were gathered by the AFIP and the American Registry of Pathology (ARP) and have been used in research and education in radiology and other fields (ophthalmology, otalaryngology, dermatology, obstetrics and gynecology, and surgery). Despite the contributions of the AFIP, the ARP, and the Radiologic Pathology Correlation Course, high-ranking members of the military and the federal government frowned on a military-owned educational system that also served civilians. Although support from the radiology community dissuaded military officers and federal officials from taking action against the participation of civilians, the 2005 Base Realignment and Closure (BRAC) provisions mandated the disestablishment of the AFIP, forcing the redistribution of some of its resources to other military-only organizations and disbanding other AFIP functions. To ensure that the correlation course, known to radiology residents as the "rad-path" course, was not a casualty of the BRAC, the American College of Radiology (ACR) and leaders of the AFIP and ARP agreed that the ACR should continue this vital educational endeavor. In January 2011, the American Institute for Radiologic Pathology of the ACR debuted and successfully instructed 268 radiology residents, including 40 international residents. The faculty and staff, who had been part of the course at the AFIP, continue to help enrich and improve the course established by their predecessors.

  6. Radiologic-Pathologic Correlation of Hepatocellular Carcinoma Treated with Chemoembolization

    SciTech Connect

    Riaz, Ahsun; Lewandowski, Robert J.; Kulik, Laura; Ryu, Robert K.; Mulcahy, Mary F.; Baker, Talia; Gates, Vanessa; Nayar, Ritu; Wang, Ed; Miller, Frank H.; Sato, Kent T.; Omary, Reed A.; Abecassis, Michael; Salem, Riad

    2010-12-15

    To correlate posttreatment radiologic and pathologic findings in patients who underwent transarterial chemoembolization before transplantation or resection. Thirty-five patients with postchemoembolization follow-up imaging underwent liver transplantation/resection. Pre- and posttreatment contrast-enhanced magnetic resonance imaging were used to evaluate radiologic findings. Imaging characteristics using World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria after treatment were evaluated. Treated lesions were examined by pathology (gold standard) for the assessment of necrosis. Radiologic findings on magnetic resonance imaging were correlated to pathologic findings to assess the predictability by imaging of actual necrosis. Kappa ({kappa}) statistics were used to determine intermethod agreement between WHO and EASL criteria. Fourteen (40%) of 35 lesions had biopsy-proven hepatocellular carcinoma. Thirteen (37%) of 35 target lesions showed complete pathologic necrosis. Complete pathologic necrosis was seen in 35% of lesions with pretreatment size <3 cm. Complete pathologic necrosis was seen in 1 (100%) of 1, 6 (67%) of 9, 6 (33%) of 18, and 0 (0%) of 7 of the lesions that exhibited complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by WHO criteria, respectively. Complete pathologic necrosis was seen in 9 (82%) of 11, 4 (36%) of 11, 0 (0%) of 8, and 0 (0%) of 5 of the lesions that showed CR, PR, SD, or PD by EASL criteria, respectively. EASL CR and WHO response were shown to have {>=}85% specificity for predicting complete pathologic necrosis. The {kappa} coefficient for agreement between WHO and EASL was 0.29. EASL and WHO criteria had minimal intermethod agreement. EASL CR and WHO response were able to predict pathologic necrosis.

  7. CT of xanthogranulomatous pyelonephritis: radiologic-pathologic correlation

    SciTech Connect

    Goldman, S.M.; Hartman, D.S.; Fishman, E.K.; Finizio, J.P.; Gatewood, O.M.B.; Siegelman, S.S.

    1984-05-01

    A clinical-radiologic-patholoigc correlation study was performed in 18 (17 female) patients with xanthogranulomatous pyelonephritis (XGP) with CT scans available for analysis. In 14 patients, the disease was diffuse; the kidney was enlarged with preservation of the reniform outline in 13. The renal pelvis, lined with sheets of lipid-laden macrophages and surrounded by a marked fibrotic reaction, was contracted in 11 and contained pelvic calculi in 12. There was CT identification of unsuspected extension through the renal capsule with involvement of the perirenal space in 11 patients, the pararenal spaces in 13, and the psoas muscle in six. There were four cases of focal XGP that appeared on CT as low-density mass lesions with wall enhancement surrounding dilated, stone-filled calices or as focal masses occupying one pole of a duplication. The preoperative diagnosis of XGP was suspected in only 44% of cases. It is concluded that CT should play a role in diagnosis and preoperative planning to demonstrate the extent of extrarenal disease that is poorly depicted by other means.

  8. Eumycetoma Osteomyelitis of the Calcaneus in a Child: A Radiologic-Pathologic Correlation following Total Calcanectomy

    PubMed Central

    EL-Sobky, Tamer Ahmed; Haleem, John Fathy; Samir, Shady

    2015-01-01

    Fungi are unusual causes of pedal osteomyelitis in children and adolescents. Eumycetoma is a chronic cutaneous and subcutaneous infection caused by various genera of fungi. A provisional diagnosis of foot mycetoma is made after clinical assessment. Radiologic-pathologic correlation is an essential supplement for the accurate diagnosis of osteoarticular infections. This paper aims to sensitize orthopedic surgeons, radiologists, and pathologists to the importance of correlative imaging findings in relation to surgical and microscopic pathology in osteoarticular infections, specifically eumycetoma osteomyelitis of the foot. From our review of the published data, the present case is the first report of radiologic-pathologic correlation in eumycetoma osteomyelitis of the calcaneus. This paper describes a case of eumycetoma osteomyelitis of the calcaneus in a child in which diagnostic X-rays and magnetic resonance imaging (MRI) were correlated with the surgical and microscopic pathologic features, for establishing an appropriate diagnosis and treatment. We conclude that there is a significant agreement between radiologic and pathologic evaluation for assessment of eumycetoma osteomyelitis of the calcaneus. Radiologic-pathologic correlation amplified our interpretation of imaging information available on plain radiographs and MRI and augmented diagnostic confidence. Similarly, anatomic-histopathological correlations consolidated diagnostic accuracy. PMID:26483983

  9. Cystic lung lesions in Sjogren syndrome: analysis of lymphocyte subsets in tissue with clinico-radiologic-pathologic correlation.

    PubMed

    Jagirdar, Jaishree; Chikkamuniyappa, Shylashree; Sirohi, Deepika; McCarthy, Michael J; Peters, Jay I

    2013-02-01

    Pulmonary complications associated with Sjögren syndrome (SS) have attracted attention in recent years. Sjögren syndrome has been associated with small cyst formation in salivary glands, thymus, and lungs and has been recently brought to the forefront by radiologists due to high-resolution techniques. However, pathologists are less aware of this finding unless clinico-radiologic-pathologic correlation is sought. Formation of large bullae in SS is a rare complication with potential for confusion with other diseases. Here, we present the clinical, radiologic, and pathologic findings in 3 patients with SS associated with multiple pulmonary cystic lesions. All 3 patients had a variable mixed restrictive and obstructive component of the disease. There was good correlation with the pulmonary function tests (PFTs), high-resolution computed tomographic scan, and morphology with regard to the restrictive component. The small cysts appear to correlate with the extent of obstructive changes on the PFTs. However, the large bullae do not, implying noncommunication with the conducting airways. This noncorrelation between the PFTs and extent of bullous disease with predominant involvement of lower lobes in SS enables distinction from bullous emphysema. The mechanism of bulla formation in SS appears to be different from bullous emphysema. A check valve mechanism has been proposed previously in SS, which does not explain cyst formation in the thymus. Alternately, inflammation may play a role with the key suspects being CD4 T-helper cells and perhaps NK cells. This is the first report of a clinico-radiologic-pathologic correlation with analysis of lymphocyte subsets.

  10. Radiological-Pathological Correlations Following Blast-Related Traumatic Brain Injury in the Whole Human Brain Using ex Vivo Diffusion Tensor Imaging

    DTIC Science & Technology

    2014-01-01

    2-0072 TITLE: Radiological -Pathological Correlations Following Blast-Related Traumatic Brain Injury in the Whole Human Brain Using ex Vivo...January 2014 2. REPORT TYPE Annual 3. DATES COVERED (From - To) 1 January 2012-31 December 2013 4. TITLE AND SUBTITLE Radiological -Pathological... radiological -pathological correlations using whole human brains from civilian TBI fatalities and US military fatalities caused by blast-related

  11. Solid pseudopapillary neoplasm of the pancreas: CT imaging features and radiologic-pathologic correlation

    PubMed Central

    Anil, Gopinathan; Zhang, Junwei; Al-Hamar, Nawal Ebrahim; Nga, Min En

    2017-01-01

    PURPOSE We aimed to evaluate the imaging features of solid pseudopapillary neoplasm (SPN) of the pancreas with an emphasis on radiologic-pathologic correlation. METHODS Ten patients (all female; mean age, 32 years) with histologic or cytologic diagnosis of SPN encountered between January 2007 and December 2013 were included in this study. Preoperative computed tomography (CT) images were reviewed for location, attenuation, enhancement pattern, margin, shape, size, morphology, presence of capsule and calcification. CT appearances were correlated with histopathologic findings. RESULTS Tumors in the distal pancreatic body and tail had a tendency to be larger (mean size 12.6 cm vs. 4.0 cm). Six of the nine tumors that were resected had a fibrous pseudocapsule at histology, five of which could be identified on CT scan. Eight lesions had mixed hypoenhancing solid components and cystic areas corresponding to tumor necrosis and hemorrhage. The two smallest lesions were purely solid and nonencapsulated. Varied patterns of calcification were seen in four tumors. Three of the four pancreatic tail tumors invaded the spleen. At a median follow-up of 53 months, there was no evidence of recurrence in the nine patients who underwent surgical resection of the tumor. CONCLUSION A mixed solid and cystic pancreatic mass in a young woman is suggestive of SPN. However, smaller lesions may be completely solid. Splenic invasion can occur in pancreatic tail SPNs; however, in this series it did not adversely affect the long-term outcome. PMID:28089954

  12. Infantile hemangioendothelioma of the liver: a radiologic-pathologic-clinical correlation

    SciTech Connect

    Dachman, A.H.; Lichtenstein, J.E.; Friedman, A.C.; Hartman, D.S.

    1983-06-01

    Infantile hemangioendothelioma is the most common symptomatic vascular liver tumor of infancy. It is considered a benign tumor; however, aggressive behavior is occasionally seen microscopically, and rarely distant metastases have been reported. The exact incidence of infantile hemangioendothelioma is difficult to determine because often it has been either misdiagnosed or mislabeled as cavernous hemangioma in the literature. Cavernous hemangioma is the most common primary liver tumor in older age groups but is rarely found in infants as a clinically significant tumor. Levick and Rubie were the first to recognize an association between hemangioendothelioma of the liver and congestive heart failure, and there were subsequent reports substantiating this association. However, it is our impression and the finding of others that congestive heart failure is distinctly less common than abdominal mass or hepatomegaly as the presenting sign in infantile hemangioendothelioma. Congestive heart failure is rarely a feature of cavernous hemangioma. Because of the errors in terminology and questions regarding clinical presentation, a radiologic-pathologic-clinical correlation study of infantile hemangioendothelioma and review of the literature was undertaken.

  13. Bacterial, Fungal, and Parasitic Infections of the Central Nervous System: Radiologic-Pathologic Correlation and Historical Perspectives.

    PubMed

    Shih, Robert Y; Koeller, Kelly K

    2015-01-01

    Despite remarkable progress in prevention and treatment, infectious diseases affecting the central nervous system remain an important source of morbidity and mortality, particularly in less-developed countries and in immunocompromised persons. Bacterial, fungal, and parasitic pathogens are derived from living organisms and affect the brain, spinal cord, or meninges. Infections due to these pathogens are associated with a variety of neuroimaging patterns that can be appreciated at magnetic resonance imaging in most cases. Bacterial infections, most often due to Streptococcus, Haemophilus, and Neisseria species, cause significant meningitis, whereas the less common cerebritis and subsequent abscess formation have well-documented progression, with increasingly prominent altered signal intensity and corresponding contrast enhancement. Atypical bacterial infections are characterized by the development of a granulomatous response, classically seen in tuberculosis, in which the tuberculoma is the most common parenchymal form of the disease; spirochetal and rickettsial diseases are less common. Fungal infections predominate in immunocompromised hosts and are caused by yeasts, molds, and dimorphic fungi. Cryptococcal meningitis is the most common fungal infection, whereas candidiasis is the most common nosocomial infection. Mucormycosis and aspergillosis are characterized by angioinvasiveness and are associated with high morbidity and mortality among immunocompromised patients. In terms of potential exposure in the worldwide population, parasitic infections, including neurocysticercosis, toxoplasmosis, echinococcosis, malaria, and schistosomiasis, are the greatest threat. Rare amebic infections are noteworthy for their extreme virulence and high mortality. The objective of this article is to highlight the characteristic neuroimaging manifestations of bacterial, fungal, and parasitic diseases, with emphasis on radiologic-pathologic correlation and historical perspectives.

  14. Fungal diseases mimicking primary lung cancer: radiologic-pathologic correlation.

    PubMed

    Gazzoni, Fernando F; Severo, Luiz Carlos; Marchiori, Edson; Irion, Klaus L; Guimarães, Marcos D; Godoy, Myrna C; Sartori, Ana P G; Hochhegger, Bruno

    2014-04-01

    A variety of fungal pulmonary infections can produce radiologic findings that mimic lung cancers. Distinguishing these infectious lesions from lung cancer remains challenging for radiologists and clinicians. In such cases, radiographic findings and clinical manifestations can be highly suggestive of lung cancer, and misdiagnosis can significantly delay the initiation of appropriate treatment. Likewise, the findings of imaging studies cannot replace the detection of a species as the aetiological agent. A biopsy is usually required to diagnose the infectious nature of the lesions. In this article, we review the clinical, histologic and radiologic features of the most common fungal infections that can mimic primary lung cancers, including paracoccidioidomycosis, histoplasmosis, cryptococcosis, coccidioidomycosis, aspergillosis, mucormycosis and blastomycosis.

  15. Myofibroblastoma of the male breast: a rare entity with radiologic-pathologic correlation.

    PubMed

    Comer, John D; Cui, Xiaoyan; Eisen, Carolyn Sharyn; Abbey, Genevieve; Arleo, Elizabeth Kagan

    A 73-year old man with a history of multiple genitourinary malignancies was found to have a left retroareolar soft tissue mass on CT assessment of disease, and dedicated breast imaging was recommended. Diagnostic mammography and ultrasonography confirmed a solid mass, for which biopsy was recommended. Pathologic analysis demonstrated a spindle cell neoplasm with an immunoreactivity pattern consistent with myofibroblastoma. While this entity is benign, nonspecific imaging features necessitate tissue sampling for pathologic diagnosis, and, given pathologic rarity, open communication between the radiologist and pathologist is important to establish the correct diagnosis and to recommend appropriate management.

  16. Computed tomography of the anterior mediastinum in myasthemia gravis: a radiologic-pathologic correlative study

    SciTech Connect

    Fon, G.T.; Bein, M.E.; Mancuso, A.A.; Keesey, J.C.; Lupetin, A.R.; Wong, W.S.

    1982-01-01

    Chest radiographs and computed tomographic (CT) scans of the mediastinum were correlated with pathologic findings of the thymus following thymectomy in 57 patients with myasthenia gravis. Based on the patient's age and the overall morphology of the anterior mediastinum, CT scans were assigned one of four grades in an attempt to predict thymus pathologic findings. Using this grading, 14 of 16 cases of thymoma were suspected or definitely diagnosed. One of the two cases not diagnosed on CT was a microscopic tumor. There were no false-positive diagnoses in 11 cases graded as definitely thymoma. We conclude that thymoma can be sensitively diagnosed in patients older than 40 years of age. However, thymoma cannot be predicted with a high level of confidence in patients younger than 40 because of the difficulty in differentiating normal thymus or hyperplasia from thymoma. Recommendations for the use of CT in the preoperative evaluation of myasthenic patients are presented.

  17. From the archives of the AFIP: breast masses in children and adolescents: radiologic-pathologic correlation.

    PubMed

    Chung, Ellen M; Cube, Regino; Hall, Gregory J; González, Candela; Stocker, J Thomas; Glassman, Leonard M

    2009-01-01

    The spectrum of breast lesions in children and adolescents varies markedly from that for adults, with the former lesions being overwhelmingly benign. A breast mass in a young boy or girl may arise from normal and abnormal breast development. Other causes of masses include infection, trauma, and cyst formation. After onset of puberty, most cases of breast enlargement arise from benign fibroadenoma in girls and gynecomastia in boys. These conditions have specific imaging appearances, although juvenile (often giant) fibroadenoma cannot be distinguished from phyllodes tumor, which can be benign or malignant. In children, both conditions usually appear as well-circumscribed, hypoechoic masses at sonography and show diffuse enhancement except for nonenhancing septations at magnetic resonance imaging. A diagnosis of juvenile papillomatosis (a benign lesion) portends later development of breast cancer, and patients with this condition should be closely monitored. Malignant lesions of the breast in children are rare. The most common malignant lesions are metastases and are usually associated with widespread disease. The most common primary breast malignancy is malignant phyllodes tumor. Primary breast carcinoma is exceedingly rare in the pediatric age group, but its imaging appearance in children is the same as seen in adults and is different from that of almost all benign lesions. In girls, diagnostic interventions may injure the developing breast and cause subsequent disfigurement. Given this risk and the low prevalence of malignant disease in this population, a prudent course should be followed in the diagnosis of breast lesions. Imaging findings are very helpful for selecting patients for further diagnostic procedures. Although malignancy is rare, lesions with suspicious imaging findings or progressive growth should be subjected to cytologic or histologic examination.

  18. Ten uncommon and unusual variants of renal angiomyolipoma (AML): radiologic-pathologic correlation.

    PubMed

    Schieda, N; Kielar, A Z; Al Dandan, O; McInnes, M D F; Flood, T A

    2015-02-01

    Classic (triphasic) renal angiomyolipoma (AML) is currently classified as a neoplasm of perivascular epithelioid cells. For diagnosis of AML, the use of thin-section non-contrast enhanced CT (NECT) improves diagnostic accuracy; however, identifying gross fat within a very small AML is challenging and often better performed with chemical-shift MRI. Although the presence of gross intra-tumoural fat is essentially diagnostic of AML; co-existing intra-tumoural fat and calcification may represent renal cell carcinoma (RCC). Differentiating AML from retroperitoneal sarcoma can be difficult when AML is large; the feeding vessel and claw signs are suggestive imaging findings. AML can haemorrhage, with intra-tumoural aneurysm size >5 mm a more specific predictor of future haemorrhage than tumor size >4 cm. Diagnosis of AML in the setting of acute haemorrhage is complex; comparison studies or follow-up imaging may be required. Not all AML contain gross fat and imaging features of AML without visible fat overlap with RCC; however, homogeneity, hyperdensity at NECT, low T2-weighted signal intensity and, microscopic fat are suggestive features. Patients with tuberous sclerosis often demonstrate a combination of classic and minimal fat AML, but are also at a slightly increased risk for RCC and should be imaged cautiously. Several rare pathological variants of AML exist including AML with epithelial cysts and epithelioid AML, which have distinct imaging characteristics. Classic AML, although benign, can be locally invasive and the rare epithelioid AML can be frankly malignant. The purpose of this review is to highlight the imaging manifestations of 10 uncommon and unusual variants of AML using pathological correlation.

  19. Optical mammography: a new technique for visualizing breast lesions in women presenting non palpable BIRADS 4-5 imaging findings: preliminary results with radiologic-pathologic correlation.

    PubMed

    Athanasiou, Alexandra; Vanel, Daniel; Fournier, Laure; Balleyguier, Corinne

    2007-02-28

    The purpose of this prospective study is to determine the diagnostic accuracy of near-infrared breast optical absorption imaging in patients with Breast Imaging Reporting and Data System (BIRADS) 4-5 non-palpable lesions scheduled for biopsy, using pathology after core or excisional biopsy as a reference. The patient's breast was positioned onto a panel of red light-emitting diodes (640 nm). A soft membrane was inflated to exert a uniform pressure on the breast. Transmitted light was detected using a CCD camera. The entire acquisition sequence took 1 minute. Image processing generated dynamic images displayed in colour scale, to reveal time-dependent changes in the transmitted light intensity caused by the pressure change. Dynamic curves were classified in two categories: consistently decreasing intensity suspicious for malignancy, and sinusoidal increasing intensity considered as benign. Seventy-eight women consulting for non-palpable breast lesions were initially included in the study. An imaging-histology correlation was obtained for seventy-two patients, the remaining six patients were excluded for technical optical scan reasons. We experienced an overall sensitivity of 73% and specificity of 38%, the false negative results being mainly small size (<10 mm) infiltrating malignant lesions and ductal carcinoma in situ (DCIS). False positive results were seen in benign proliferative lesions. Dynamic optical breast imaging is a novel, low-cost, non-invasive technique yielding a new type of information about the physiology of breast lesions. Absorption is due to haemoglobin and its products, therefore reflecting the angiogenic status of breast tumours.

  20. [Dedifferentiated chondrosarcoma: radiologic-pathologic correlation].

    PubMed

    Bierry, G; Feydy, A; Larousserie, F; Pluot, E; Guerini, H; Campagna, R; Dufau-Andreu, C; Anract, P; Babinet, A; Dietemann, J L; Chevrot, A; Drapé, J L

    2010-03-01

    Dedifferentiated chondrosarcomas are highly malignant tumors characterized by conventional low-grade chondrosarcoma with abrupt transition to foci that have dedifferentiated into a higher-grade noncartilaginous more aggressive sarcoma. The dedifferentiated component, an osteosarcoma or fibrosarcoma, determines the prognosis. Its identification is key for management. A diagnosis of dedifferentiated chondrosarcoma should be suggested by the presence of "tumoral dimorphism" with cartilaginous component and aggressive lytic component invading adjacent soft tissues.

  1. Paratesticular Liposarcoma: A Radiologic Pathologic Correlation

    PubMed Central

    Pergel, Ahmet; Yucel, Ahmet Fikret; Aydin, Ibrahim; Sahin, Dursun Ali; Gucer, Hasan; Kocakusak, Ahmet

    2011-01-01

    Spermatic cord liposarcoma is an uncommon paratesticular tumor. Patients usually present with a painless scrotal or inguinal mass, mimicking inguinal hernia. Clinical examination suggested an inguinal hernia. Computed tomography demonstrated a fat-containing mass in the right inguinal region. The mass was surgically removed, along with the right testis and spermatic cord. Histopathological examination revealed a well-differentiated liposarcoma. No evidence of recurrence or metastases has been noted during the two-year follow-up with postoperative adjuvant therapy. PMID:22267992

  2. Radiology-pathology conference: cutaneous angiosarcoma of the leg.

    PubMed

    Linda, Dorota D; Harish, Srinivasan; Alowami, Salem; DeNardi, Franco; Deheshi, Benjamin M

    2013-01-01

    Cutaneous angiosarcoma is a rare aggressive vascular neoplasm with a poor prognosis, seen usually in the elderly population in a background of chronic lymphedema. We present a case of cutaneous angiosarcoma of the leg without any chronic lymphedema with clinicoradiological and histological correlation.

  3. Genitourinary schistosomiasis: life cycle and radiologic-pathologic findings.

    PubMed

    Shebel, Haytham M; Elsayes, Khaled M; Abou El Atta, Heba M; Elguindy, Yehia M; El-Diasty, Tarek A

    2012-01-01

    Genitourinary schistosomiasis is produced by Schistosoma haematobium, a species of fluke that is endemic to Africa and the Middle East, and causes substantial morbidity and mortality in those regions. It also may be seen elsewhere, as a result of travel or immigration. S haematobium, one of the five fluke species that account for most human cases of schistosomiasis, is the only species that infects the genitourinary system, where it may lead to a wide spectrum of clinical symptoms and signs. In the early stages, it primarily involves the bladder and ureters; later, the kidneys and genital organs are involved. It rarely infects the colon or lungs. A definitive diagnosis of genitourinary schistosomiasis is based on findings of parasite ova at microscopic urinalysis. Clinical manifestations and radiologic imaging features also may be suggestive of the disease, even at an early stage: Hematuria, dysuria, and hemospermia, early clinical signs of an established S haematobium infection, appear within 3 months after infection. At imaging, fine ureteral calcifications that appear as a line or parallel lines on abdominopelvic radiographs and as a circular pattern on axial images from computed tomography (CT) are considered pathognomonic of early-stage schistosomiasis. Ureteritis, pyelitis, and cystitis cystica, conditions that are characterized by air bubble-like filling defects representing ova deposited in the ureter, kidney, and bladder, respectively, may be seen at intravenous urography, intravenous ureteropyelography, and CT urography. Coarse calcification, fibrosis, and strictures are signs of chronic or late-stage schistosomiasis. Such changes may be especially severe in the bladder, creating a predisposition to squamous cell carcinoma. Genital involvement, which occurs more often in men than in women, predominantly affects the prostate and seminal vesicles.

  4. Ileostomy obstruction by ingested apricot stone with clinical-radiological-pathological correlation.

    PubMed

    George, A J; Fallaize, R C; Bennett, J; Shabbir, J

    2015-09-15

    Patients with stomas often present with bowel obstruction, often secondary to adhesions. This case describes the presentation, investigation and management of a 62-year-old woman with an end ileostomy, who presented to hospital with acute abdominal pain and subacute bowel obstruction. Further questioning revealed the recent ingestion of an apricot stone and this was identified by multimodality imaging as the cause of the luminal obstruction in the distal ileum, just proximal to the stoma. After a failed period of conservative management, examination under anaesthesia was performed and digital extraction attempted, but this was unsuccessful. Rather than surgical stoma revision, endoscopic removal was achieved. The patient improved and was discharged the following day. However, her small bowel obstruction relapsed within 48 h. She was readmitted and underwent stoma revision with no further problems.

  5. Tomosynthesis-detected Architectural Distortion: Management Algorithm with Radiologic-Pathologic Correlation.

    PubMed

    Durand, Melissa A; Wang, Steven; Hooley, Regina J; Raghu, Madhavi; Philpotts, Liane E

    2016-01-01

    As use of digital breast tomosynthesis becomes increasingly widespread, new management challenges are inevitable because tomosynthesis may reveal suspicious lesions not visible at conventional two-dimensional (2D) full-field digital mammography. Architectural distortion is a mammographic finding associated with a high positive predictive value for malignancy. It is detected more frequently at tomosynthesis than at 2D digital mammography and may even be occult at conventional 2D imaging. Few studies have focused on tomosynthesis-detected architectural distortions to date, and optimal management of these distortions has yet to be well defined. Since implementing tomosynthesis at our institution in 2011, we have learned some practical ways to assess architectural distortion. Because distortions may be subtle, tomosynthesis localization tools plus improved visualization of adjacent landmarks are crucial elements in guiding mammographic identification of elusive distortions. These same tools can guide more focused ultrasonography (US) of the breast, which facilitates detection and permits US-guided tissue sampling. Some distortions may be sonographically occult, in which case magnetic resonance imaging may be a reasonable option, both to increase diagnostic confidence and to provide a means for image-guided biopsy. As an alternative, tomosynthesis-guided biopsy, conventional stereotactic biopsy (when possible), or tomosynthesis-guided needle localization may be used to achieve tissue diagnosis. Practical uses for tomosynthesis in evaluation of architectural distortion are highlighted, potential complications are identified, and a working algorithm for management of tomosynthesis-detected architectural distortion is proposed.

  6. Soft-Tissue Sarcomas of the Abdomen and Pelvis: Radiologic-Pathologic Features, Part 1-Common Sarcomas: From the Radiologic Pathology Archives.

    PubMed

    Levy, Angela D; Manning, Maria A; Al-Refaie, Waddah B; Miettinen, Markku M

    2017-01-01

    Soft-tissue sarcomas are a diverse group of rare mesenchymal malignancies that can arise at any location in the body and affect all age groups. These sarcomas are most common in the extremities, trunk wall, retroperitoneum, and head and neck. In the adult population, soft-tissue sarcomas arising in the abdomen and pelvis are often large masses at the time of diagnosis because they are usually clinically silent or cause vague or mild symptoms until they invade or compress vital organs. In contrast, soft-tissue sarcomas arising from the abdominal wall come to clinical attention earlier in the course of disease because they cause a palpable mass, abdominal wall deformity, or pain that is more clinically apparent. The imaging features of abdominal and pelvic sarcomas and abdominal wall sarcomas can be nonspecific and overlap with more common pathologic conditions, making diagnosis difficult or, in some cases, delaying diagnosis. Liposarcoma (well-differentiated and dedifferentiated liposarcomas), leiomyosarcoma, and gastrointestinal stromal tumor (GIST) are the most common intra-abdominal primary sarcomas. Any soft-tissue sarcoma can arise in the abdominal wall. Knowledge of the classification and pathologic features of soft-tissue sarcomas, the anatomic locations where they occur, and their cross-sectional imaging features helps the radiologist establish the diagnosis or differential diagnosis so that patients with soft-tissue sarcomas can receive optimal treatment and management. In part 1 of this article, the most common soft-tissue sarcomas (liposarcoma, leiomyosarcoma, and GIST) are reviewed, with a discussion on anatomic locations, classification, clinical considerations, and differential diagnosis. Part 2 will focus on the remainder of the soft-tissue sarcomas occurring in the abdomen and pelvis.

  7. Radiologic-Pathologic Analysis of Contrast-enhanced and Diffusion-weighted MR Imaging in Patients with HCC after TACE: Diagnostic Accuracy of 3D Quantitative Image Analysis

    PubMed Central

    Chapiro, Julius; Wood, Laura D.; Lin, MingDe; Duran, Rafael; Cornish, Toby; Lesage, David; Charu, Vivek; Schernthaner, Rüdiger; Wang, Zhijun; Tacher, Vania; Savic, Lynn Jeanette; Kamel, Ihab R.

    2014-01-01

    standard error [RSEresidual standard error] = 6.38 and 6.33 for quantitative EASLEuropean Association for the Study of the Liver and quantitative ADCapparent diffusion coefficient, respectively), when compared with non-3Dthree-dimensional techniques (RSEresidual standard error = 12.18 for visual assessment). Conclusion This radiologic-pathologic correlation study demonstrates the diagnostic accuracy of 3Dthree-dimensional quantitative MR imaging techniques in identifying pathologically measured tumor necrosis in HCChepatocellular carcinoma lesions treated with TACEtransarterial chemoembolization. © RSNA, 2014 Online supplemental material is available for this article. PMID:25028783

  8. Ectopic Anterior Mediastinal Pathology in the Chest: Radiologic-pathologic Correlation of Unexpected Encounters with the “Terrible Ts”

    PubMed Central

    Rashidfarokhi, Mahsan; Gupta, Jessica; Leytin, Anatoly; Epelbaum, Oleg

    2016-01-01

    The complex embryology of the anterior mediastinum makes it home to an array of primary neoplasms tied to the presence of the thyroid and thymus glands in that compartment. While the occurrence of ectopic thyroid deposits in the extramediastinal thorax has not been convincingly established, the other three “Ts” of the classic “4T” mnemonic for the differential diagnosis of an anterior mediastinal mass have occurred in the lung parenchyma, pleural space, and endobronchially as primary tumors. Finding any of the three lesions – thymoma, teratoma, or B-cell lymphoma – in the chest outside the mediastinum is very unusual, but that possibility exists. Herein, we illustrate examples of this rare phenomenon. PMID:28123839

  9. Calcifying Epithelial Odontogenic Tumor of the Mandible (Pindborg Tumor) . RPC (Radiologic-Pathologic Correlation) from the AFIP

    DTIC Science & Technology

    radiolucent to chiefly radiopaque. The size of the slowly-growing lesion corresponds to its duration. The differential diagnosis should include adenoameloblastoma, odontoma , ossifying fibroma, and osteomyelitis.

  10. [Correlation of chronic periodontal disease and cardiovascular disease].

    PubMed

    Grudyanov, A I; Tkacheva, O N; Avraamova, T V

    2017-01-01

    The aim of the study was to assess correlative risk of progression of inflammatory periodontal lesions, the development of a systemic inflammatory reaction and cardiovascular diseases. The study involved 89 patients with chronic periodontal disease (CPD) of varying degrees. High cardiovascular disease risk was revealed in 8.8% of patients with moderate and 13.3% of patients with severe periodontal disease. It is proved that an additional factor contributing to the pathogenic relationship between periodontal inflammatory changes and the development of cardiovascular disease is systemic inflammatory response with increased hrC-reactive protein >3.4 mg/l and interleukin-6 to11.0±3.4 mg/l. Changes of blood lipid spectrum with a reduction in apolipoprotein A1 were associated with progression and development of the CPD. Correlations of somatic and dental pathology requires dentists and cardiologists joint efforts to modify common risk factors.

  11. Radiologic-pathologic findings of primary osseous adamantinoma with unusual metastasis to the posterior cul-de-sac in pregnancy.

    PubMed

    Flug, Jonathan A; Scalcione, Luke R; Hakima, Laleh; Ganson, George; Mazzie, Joseph P; Katz, Douglas S; Brooks, Michael

    2011-01-01

    Adamantinoma is a rare primary bone malignancy with a predilection for the tibial cortex. Metastases have been reported to the long bones, lung, pleura and spine. We present a 26-year-old pregnant woman with metastatic disease to the posterior cul-de-sac, lungs, liver and retroperitoneum, which collectively have not been previously reported in a single patient to our knowledge.

  12. Cognitive Correlates of Metamemory in Alzheimer's Disease

    PubMed Central

    Shaked, Danielle; Farrell, Meagan; Huey, Edward; Metcalfe, Janet; Cines, Sarah; Karlawish, Jason; Sullo, Elisabeth; Cosentino, Stephanie

    2014-01-01

    Objective Metamemory, or knowledge of one's memory abilities, is often impaired in individuals with Alzheimer's disease (AD), although the basis of this metacognitive deficit has not been fully articulated. Behavioral and imaging studies have produced conflicting evidence regarding the extent to which specific cognitive domains (i.e., executive functioning (EF), memory) and brain regions contribute to memory awareness. The primary aim of this study was to disentangle the cognitive correlates of metamemory in AD by examining the relatedness of objective metamemory performance to cognitive tasks grouped by domain (EF or memory) as well as by preferential hemispheric reliance defined by task modality (verbal or nonverbal). Method 89 participants with mild AD recruited at Columbia University Medical Center and the University of Pennsylvania underwent objective metamemory and cognitive testing. Partial correlations were used to assess the relationship between metamemory and four cognitive variables, adjusted for recruitment site. Results The significant correlates of metamemory included nonverbal fluency (r = .27 p = .02) and nonverbal memory (r = .24, p = .04). Conclusions Our findings suggest that objectively measured metamemory in a large sample of individuals with mild AD is selectively related to a set of inter-domain nonverbal tasks. The association between metamemory and the nonverbal tasks may implicate a shared reliance on a right-sided cognitive network that spans frontal and temporal regions. PMID:24819066

  13. Dermopathy of Graves' disease: Clinico-pathological correlation.

    PubMed

    Reddy, Sagili Vijaya Bhaskar; Gupta, Sushil Kumar; Jain, Manoj

    2012-05-01

    Dermopathy of Graves' disease is a classical, but uncommon extrathyroidal manifestation of Graves' disease. The images of a typical case of dermopathy of Graves' disease are presented along with clinico-pathological correlation.

  14. Neural correlates underlying micrographia in Parkinson's disease.

    PubMed

    Wu, Tao; Zhang, Jiarong; Hallett, Mark; Feng, Tao; Hou, Yanan; Chan, Piu

    2016-01-01

    Micrographia is a common symptom in Parkinson's disease, which manifests as either a consistent or progressive reduction in the size of handwriting or both. Neural correlates underlying micrographia remain unclear. We used functional magnetic resonance imaging to investigate micrographia-related neural activity and connectivity modulations. In addition, the effect of attention and dopaminergic administration on micrographia was examined. We found that consistent micrographia was associated with decreased activity and connectivity in the basal ganglia motor circuit; while progressive micrographia was related to the dysfunction of basal ganglia motor circuit together with disconnections between the rostral supplementary motor area, rostral cingulate motor area and cerebellum. Attention significantly improved both consistent and progressive micrographia, accompanied by recruitment of anterior putamen and dorsolateral prefrontal cortex. Levodopa improved consistent micrographia accompanied by increased activity and connectivity in the basal ganglia motor circuit, but had no effect on progressive micrographia. Our findings suggest that consistent micrographia is related to dysfunction of the basal ganglia motor circuit; while dysfunction of the basal ganglia motor circuit and disconnection between the rostral supplementary motor area, rostral cingulate motor area and cerebellum likely contributes to progressive micrographia. Attention improves both types of micrographia by recruiting additional brain networks. Levodopa improves consistent micrographia by restoring the function of the basal ganglia motor circuit, but does not improve progressive micrographia, probably because of failure to repair the disconnected networks.

  15. Electroencephalographic correlate of juvenile Huntington's disease.

    PubMed

    Ullrich, Nicole J; Riviello, James J; Darras, Basil T; Donner, Elizabeth J

    2004-07-01

    The spectrum of clinical disease in juvenile Huntington's disease differs from that seen in adults. Younger patients often present with seizures, dystonia and rigidity. The mechanism and type of seizures, timing of onset and electrographic features have not been well characterized in either adults or children. We describe the electroencephalographic findings observed in a young child with Huntington's disease who presented with motor regression and seizures. Recordings demonstrated bilateral posterior quadrant epileptiform discharges and occipital intermittent rhythmic delta activity, generally considered a nonspecific abnormality. These findings have not been reported in adult or juvenile Huntington's disease. Its presence in proximity to bilateral posterior spikes suggests that occipital intermittent rhythmic delta activity is an epileptiform abnormality, on a continuum with the posterior spike-and-wave discharges. Intermittent rhythmic delta activity can occur secondary to either the subcortical gray-matter disease or the associated seizure disorder. Huntington's disease should be considered in the differential diagnosis of young children who present with seizures and developmental regression.

  16. Data mining for correlations between diet and Crohn's disease activity.

    PubMed

    Cooper, Jason G; Purcell, Gretchen P

    2006-01-01

    Crohn's disease is a debilitating condition that affects the entire gastrointestinal tract and often requires aggressive and invasive therapies. Several studies have suggested dietary triggers for disease activity. We have created a web-based tool to allow participants to record both daily food intake and wellness (i.e., disease-specific quality of life). We seek to determine if measurable correlations exist between these events in patients with Crohn's disease. Advanced data mining techniques are employed to find such correlations and the efficacies of chosen techniques are assessed. We tested our web-based system in a pilot study involving 7 participants, and we found that traditional statistical techniques identified diet and disease activity correlations in short-term data sets.

  17. An Atlas of Genetic Correlations across Human Diseases and Traits

    PubMed Central

    Bulik-Sullivan, Brendan; Finucane, Hilary K; Anttila, Verneri; Gusev, Alexander; Day, Felix R.; Loh, Po-Ru; Duncan, Laramie; Perry, John R.B.; Patterson, Nick; Robinson, Elise B.; Daly, Mark J.; Price, Alkes L.; Neale, Benjamin M.

    2015-01-01

    Identifying genetic correlations between complex traits and diseases can provide useful etiological insights and help prioritize likely causal relationships. The major challenges preventing estimation of genetic correlation from genome-wide association study (GWAS) data with current methods are the lack of availability of individual genotype data and widespread sample overlap among meta-analyses. We circumvent these difficulties by introducing a technique – cross-trait LD Score regression – for estimating genetic correlation that requires only GWAS summary statistics and is not biased by sample overlap. We use this method to estimate 276 genetic correlations among 24 traits. The results include genetic correlations between anorexia nervosa and schizophrenia, anorexia and obesity and associations between educational attainment and several diseases. These results highlight the power of genome-wide analyses, since there currently are no significantly associated SNPs for anorexia nervosa and only three for educational attainment. PMID:26414676

  18. Prevalence and correlates of heart disease among adults in Singapore.

    PubMed

    Picco, Louisa; Subramaniam, Mythily; Abdin, Edimansyah; Vaingankar, Janhavi Ajit; Chong, Siow Ann

    2016-02-01

    Heart disease is one of the leading causes of morbidity and mortality worldwide and it has been well established that it is associated with both mental and physical conditions. This paper describes the prevalence of heart disease with mental disorders and other chronic physical conditions among the Singapore resident population. Data were from the Singapore Mental Health Study which was a representative, cross-sectional epidemiological survey undertaken with 6616 Singapore residents, between December 2009 and December 2010. The Composite International Diagnostic Interview Version 3.0 was used to establish the diagnosis of mental disorders, while a chronic medical conditions checklist was used to gather information on 15 physical conditions, including various forms of heart disease. Health-related quality of life was measured using the Euro-Quality of Life Scale (EQ-5D). The lifetime prevalence of heart disease was 2.8%. Socio-demographic correlates of heart disease included older age, Indian ethnicity, secondary education (vs. tertiary) and being economically inactive. After adjusting for socio-demographic variables and other comorbid physical and mental disorders, the prevalence of major depressive disorder and bipolar disorder were significantly higher among those with heart disease, as were diabetes, arthritis, kidney failure and lung disease. These findings highlight important associations between heart disease and various socio-demographic correlates, mental disorders and physical conditions. Given the high prevalence of mood disorders among heart disease patients, timely and appropriate screening and treatment of mental disorders among this group is essential.

  19. Radiologic-pathologic analysis of quantitative 3D tumour enhancement on contrast-enhanced MR imaging: a study of ROI placement

    PubMed Central

    Chockalingam, Arun; Duran, Rafael; Sohn, Jae Ho; Schernthaner, Rüdiger; Chapiro, Julius; Lee, Howard; Sahu, Sonia; Nguyen, Sonny; Lin, MingDe

    2015-01-01

    Objectives To investigate the influence of region-of-interest (ROI) placement on 3D tumour enhancement [Quantitative European Association for the Study of the Liver (qEASL)] in hepatocellular carcinoma (HCC) patients treated with transcatheter arterial chemoembolization (TACE). Methods Phase 1: 40 HCC patients had nine ROIs placed by one reader using systematic techniques (3 ipsilateral to the lesion, 3 contralateral to the lesion, and 3 dispersed throughout the liver) and qEASL variance was measured. Intra-class correlations were computed. Phase 2: 15 HCC patients with histosegmentation were selected. Six ROIs were systematically placed by AC (3 ROIs ipsilateral and 3 ROIs contralateral to the lesion). Three ROIs were placed by 2 radiologists. qEASL values were compared to histopathology by Pearson’s correlation, linear regression, and median difference. Results Phase 1: The dispersed method (abandoned in phase 2) had low consistency and high variance. Phase 2: qEASL correlated strongly with pathology in systematic methods [Pearson’s correlation coefficient=0.886 (ipsilateral) and 0.727 (contralateral)] and in clinical methods (0.625 and 0.879). However, ipsilateral placement matched best with pathology (median difference: 5.4 %; correlation: 0.89; regression CI: [0.904, 0.1409]). Conclusions qEASL is a robust method with comparable values among tested placements. Ipsilateral placement showed high consistency and better pathological correlation. PMID:25994198

  20. Neuropathologic correlates of trial-related instruments for Alzheimer's disease.

    PubMed

    Cummings, Jeffrey L; Ringman, John; Vinters, Harry V

    2014-01-01

    To advance disease-modifying therapies, it is critical to understand the relationship between the neuropathological changes of Alzheimer's Disease (AD) and the clinical measures used in therapeutic trials. We reviewed neuropathologically proven cases of AD from the National Alzheimer's Coordinating Center (NACC) and examined correlations between neuropathological changes and clinical-trial related instruments collected as part of the Uniform Dataset (UDS). We explored the relationships between neurofibrillary tangles, neuritic plaques, and total pathology burden with immediate and delayed recall, Clinical Dementia Rating-Sum of Boxes, Functional Activity Questionnaire, Neuropsychiatric Inventory Questionnaire, and Mini-Mental State Examination scores. 169 patients in NACC database had appropriate neuropathological and clinical data. All instruments correlated highly with neuritic plaques, Braak staging, and total pathology. Correlation coefficients for the relationships were relatively modest, suggesting that the pathologic burden examined accounts for between 13 and 40% of the variance of each of the instruments assessed. We conclude that there is a strong correlation between clinical trial-related measures and neuropathology identified at autopsy in AD. The amount of variance explained by the pathology is limited and other factors, both disease- and measurement-related, contribute to the variability observed in clinical measurements.

  1. Neuropathologic correlates of activities of daily living in Alzheimer disease.

    PubMed

    Marshall, Gad A; Fairbanks, Lynn A; Tekin, Sibel; Vinters, Harry V; Cummings, Jeffrey L

    2006-01-01

    Functional status, reflected by measures of activities of daily living (ADLs), deteriorates as Alzheimer disease (AD) progresses. Decline in activities of daily living may be mediated by executive and frontal lobe dysfunction. The objective of this study was to examine the relationship between activities of daily living and pathologic burden in Alzheimer disease. Twenty two subjects with definite Alzheimer disease were selected from the UCLA ADRC neuropathology database. A total activities of daily living score was derived from the Retrospective Collateral Dementia Interview-Revised (RCDI-R) questionnaire, which was administered to caregivers of autopsied subjects included in the study. Neuritic plaque (NP) and neurofibrillary tangle (NFT) counts were performed for 8 brain regions. There was a significant positive correlation between total activities of daily living score (higher scores indicate more disability) and mean neuritic plaques and neurofibrillary tangle counts (r = 0.671, P = 0.001, and r = 0.542, P = 0.009, resp), as well as CA1 and prosubiculum neuritic plaques and neurofibrillary tangle counts, right and left orbital frontal neuritic plaques counts, and occipital neuritic plaques count. Total activities of daily living score did not correlate with age at death, age at symptom onset, dementia duration, gender, or education. Deteriorating activities of daily living in Alzheimer Disease subjects correlate with greater overall pathologic burden and possibly selectively with involvement of the medial temporal, occipital, and orbital frontal regions.

  2. Paravertebral Well-Differentiated Liposarcoma with Low-Grade Osteosarcomatous Component: Case Report with 11-Year Follow-Up, Radiological, Pathological, and Genetic Data, and Literature Review

    PubMed Central

    Fuentes, Stéphane; Maues de Paula, André; Salas, Sébastien; Mattéi, Jean-Camille; Dupuis, Charlotte; Appay, Romain; Aurias, Alain; Dufour, Henry; Figarella-Branger, Dominique; Bouvier, Corinne

    2017-01-01

    Despite being one of the most frequent soft-tissue sarcomas, well-differentiated liposarcoma has never been reported near the spine. The authors present the case of a 67-year-old man with progressive history of back pain. Physical examination revealed a mass located within the right paravertebral muscles. MR and CT imaging showed a heavily ossified central mass surrounded by a peripheral fatty component. No connection with the underlying bone was detected on imagery and during surgery. After surgical resection, histopathological examination revealed a tumor harboring combined features of well-differentiated liposarcoma and low-grade osteosarcoma. Tumor cells displayed overexpression of MDM2, CDK4, and P16 by immunohistochemistry and CGH revealed amplification of 12q13-15 as the only genetic imbalance. MDM2 FISH analysis was performed but was inconclusive. The pathological, immunohistochemical, and genetic features, the differential diagnoses, and the therapeutic management of this unusual tumor are discussed. No complementary treatment was performed initially. Following first treatment, two recurrences occurred 6 and 9 years later, both displaying histological features similar to the first occurrence. Radiotherapy was started after the second recurrence. Follow-up shows no evidence of disease 11 years after initial diagnosis. This case was unusual due to the paravertebral location of the tumor and its divergent differentiation. PMID:28377828

  3. Neurocognitive Correlates of Apathy and Anxiety in Parkinson's Disease

    PubMed Central

    Bogdanova, Yelena; Cronin-Golomb, Alice

    2012-01-01

    Parkinson's disease (PD) is associated with various nonmotor symptoms including neuropsychiatric and cognitive dysfunction. We examined the relation between apathy, anxiety, side of onset of motor symptoms, and cognition in PD. We hypothesized that PD patients would show different neuropsychiatric and neurocognitive profiles depending on the side of onset. 22 nondemented PD patients (11 right-side onset (RPD) with predominant left-hemisphere pathology, and 11 LPD) and 22 matched healthy controls (NC) were administered rating scales assessing apathy and anxiety, and a series of neuropsychological tests. PD patients showed a higher anxiety level than NC. There was a significant association between apathy, anxiety, and disease duration. In LPD, apathy but not anxiety was associated with performance on nonverbally mediated executive function and visuospatial measures, whereas, in RPD, anxiety but not apathy correlated with performance on verbally mediated tasks. Our findings demonstrated a differential association of apathy and anxiety to cognition in PD. PMID:22203919

  4. Correlations of clinical, neuroimaging, and electrophysiological features in Hirayama disease

    PubMed Central

    Liao, Ming-Feng; Chang, Hong-Shiu; Chang, Kuo-Hsuan; Ro, Long-Sun; Chu, Chun-Che; Kuo, Hung-Chou; Lyu, Rong-Kuo

    2016-01-01

    Abstract Hirayama disease (HD) is characterized by development of asymmetric forearm muscle atrophy during adolescence with or without focal cervical spinal cord atrophy. The purpose of this study is to assess the correlation of clinical symptoms, disease progression, and electrophysiological findings with cervical spine magnetic resonance imaging (MRI) findings. The medical records, cervical spine MRIs, and electrophysiological findings of 44 HD patients were retrospectively reviewed and analyzed. Denervation changes in any single C5 to C7 root-innervated muscle (deltoid, biceps, triceps, or extensor digitorum communis) occurred more frequently in the 25 patients with cord atrophy than the 19 patients without cord atrophy (88% vs 53%, P = 0.02). Onset age, duration of disease progression, neurological examinations, nerve conduction study, and electromyographic findings from individual muscles were similar between patient groups. Compared with HD patients without cord atrophy, HD patients with cord atrophy experience a more severe denervation change in C5 to C7 root-innervated muscles. PMID:27428223

  5. Impaired Pain Processing Correlates with Cognitive Impairment in Parkinson's Disease

    PubMed Central

    Okada, Akinori; Nakamura, Tomohiko; Suzuki, Junichiro; Suzuki, Masashi; Hirayama, Masaaki; Katsuno, Masahisa; Sobue, Gen

    2016-01-01

    Objective Pain and cognitive impairment are important clinical features in patients with Parkinson's disease (PD). Although pain processing is associated with the limbic system, which is also closely linked to the cognitive function, the association between pain and cognitive impairment in PD is still not well understood. The aim of the study was to investigate the association between pain processing and cognitive impairment in patients with PD. Methods Forty-three patients with PD and 22 healthy subjects were studied. Pain-related somatosensory evoked potentials (SEPs) were generated using a thin needle electrode to stimulate epidermal Aδ fibers. Cognitive impairment was evaluated using the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery, and Japanese version of the Montreal Cognitive Assessment (MoCA-J), and their correlation with pain-related SEPs was investigated. Results The N1/P1 amplitude was significantly lower in PD patients than the controls. N1/P1 peak-to-peak amplitudes correlated with the MMSE (r=0.66, p<0.001) and MoCA-J scores (r=0.38, p<0.01) in patients with PD. These amplitudes also strongly correlated with the domains of attention and memory in the MMSE (attention, r=0.52, p<0.001; memory, r=0.40, p<0.01) and MoCA-J (attention, r=0.45, p<0.005; memory, r=0.48, p<0.001), but not in control subjects. Conclusion A good correlation was observed between the decreased amplitudes of pain-related SEPs and an impairment of attention and memory in patients with PD. Our results suggest that pathological abnormalities of the pain pathway are significantly linked to cognitive impairment in PD. PMID:27803403

  6. Soil Correlates and Mortality from Giraffe Skin Disease in Tanzania.

    PubMed

    Bond, Monica L; Strauss, Megan K L; Lee, Derek E

    2016-10-01

    Giraffe skin disease (GSD) is a disorder of undetermined etiology that causes lesions on the forelimbs of Masai giraffe ( Giraffa camelopardalis tippelskirchi) in Tanzania, East Africa. We examined soil correlates of prevalence of GSD from 951 giraffe in 14 sites in Tanzania, and estimated mortality using 3 yr of longitudinal mark-recapture data from 382 giraffe with and without GSD lesions, in Tarangire National Park (TNP). Spatial variation in GSD prevalence was best explained by soil fertility, measured as cation exchange capacity. We found no mortality effect of GSD on adult giraffe in TNP. Based on our findings, GSD is unlikely to warrant immediate veterinary intervention, but continued monitoring is recommended to ensure early detection if GSD-afflicted animals begin to show signs of increased mortality or other adverse effects.

  7. Neurochemical correlates of caudate atrophy in Huntington disease

    PubMed Central

    Padowski, Jeannie M.; Weaver, Kurt E.; Richards, Todd L.; Laurino, Mercy Y.; Samii, Ali; Aylward, Elizabeth H.; Conley, Kevin E.

    2014-01-01

    BACKGROUND The precise pathogenic mechanisms of Huntington disease (HD) are unknown, but can be tested in vivo using proton magnetic resonance spectroscopy (1H MRS) to measure neurochemical changes. OBJECTIVE To evaluate neurochemical differences in HD gene mutation-carriers (HGMC) vs. controls, and to investigate relationships among function, brain structure and neurochemistry in HD. Since previous 1H MRS studies have yielded varied conclusions about HD neurochemical changes, an additional goal was to compare two 1H MRS data analysis approaches. METHODS HGMC with pre-manifest to early HD and controls underwent evaluation of motor function, MR imaging and localized 1H MRS in caudate and frontal lobe. Analytical approaches tested included absolute quantitation (unsuppressed water signal as an internal reference) and relative quantification (calculating ratios of all neurochemical signals within a voxel). RESULTS We identified a suite of neurochemicals reduced in concentration proportionally to loss of caudate volume in HGMC. Caudate concentrations of NAA, creatine, choline, and caudate and frontal concentrations of glutamate+glutamine and glutamate correlated with caudate volume in HGMC subjects. The relative, but not the absolute quantitation approach revealed disease-related differences; the Glx signal was decreased relative to other neurochemicals in caudate of HGMC subjects vs. controls. CONCLUSIONS This is the first study to demonstrate correlation among structure, function and chemical measures in HD brain. Additionally, we demonstrate that a relative quantitation approach may enable magnification of subtle differences between groups. Observation of decreased glutamate-glutamine signals suggests that glutamate signaling may be disrupted relatively early in HD, with important implications for therapeutic approaches. PMID:24442623

  8. Neurochemical correlates of caudate atrophy in Huntington's disease.

    PubMed

    Padowski, Jeannie M; Weaver, Kurt E; Richards, Todd L; Laurino, Mercy Y; Samii, Ali; Aylward, Elizabeth H; Conley, Kevin E

    2014-03-01

    The precise pathogenic mechanisms of Huntington's disease (HD) are unknown but can be tested in vivo using proton magnetic resonance spectroscopy ((1)H MRS) to measure neurochemical changes. The objective of this study was to evaluate neurochemical differences in HD gene mutation carriers (HGMCs) versus controls and to investigate relationships among function, brain structure, and neurochemistry in HD. Because previous (1)H MRS studies have yielded varied conclusions about HD neurochemical changes, an additional goal was to compare two (1)H MRS data analysis approaches. HGMCs with premanifest to early HD and controls underwent evaluation of motor function, magnetic resonance imaging, and localized (1)H MRS in the caudate and the frontal lobe. Analytical approaches that were tested included absolute quantitation (unsuppressed water signal as an internal reference) and relative quantification (calculating ratios of all neurochemical signals within a voxel). We identified a suite of neurochemicals that were reduced in concentration proportionally to loss of caudate volume in HGMCs. Caudate concentrations of N-acetylaspartate (NAA), creatine, choline, and caudate and frontal lobe concentrations of glutamate plus glutamine (Glx) and glutamate were correlated with caudate volume in HGMCs. The relative, but not the absolute, quantitation approach revealed disease-related differences; the Glx signal was decreased relative to other neurochemicals in the caudate of HGMCs versus controls. This is the first study to demonstrate a correlation among structure, function, and chemical measures in HD brain. Additionally, we demonstrate that a relative quantitation approach may enable the magnification of subtle differences between groups. Observation of decreased Glx suggests that glutamate signaling may be disrupted relatively early in HD, which has important implications for therapeutic approaches.

  9. Ocular signs correlate well with disease severity and genotype in Fabry disease.

    PubMed

    Pitz, Susanne; Kalkum, Gisela; Arash, Laila; Karabul, Nesrin; Sodi, Andrea; Larroque, Sylvain; Beck, Michael; Gal, Andreas

    2015-01-01

    Ocular signs in Fabry disease have generally been regarded to be primarily of diagnostic value. We explored whether ocular findings, alone or in particular in combination with the α-galactosidase A gene mutation, have predictive value for disease severity. Data from the Fabry Outcome Survey (FOS), a large, global database sponsored by Shire, were selected for adult patients who had undergone ophthalmological examination. Three ocular signs were assessed: cornea verticillata, tortuous conjunctival and/or retinal vessels, and cataract. Fabry disease severity was measured using FOS Mainz Severity Score Index and modifications thereof. Ophthalmological data were available for 1203 (699 female, 504 male) adult patients with eye findings characteristic of Fabry disease in 55.1%. Cornea verticillata had a similar distribution in women (51.1%) and men (50.8%), whereas tortuous vessels and Fabry cataract were somewhat more frequent in men than in women. Patients with cornea verticillata, selected as the principal ocular sign for this study, had more severe disease (median score, 20.0) versus those without ocular signs (11.0; P<0.001). This finding could be confirmed by applying age adjusted severity scores. Moreover, the prevalence of cornea verticillata was significantly higher in patients with null (male, 76.9%; female, 64.5%) and missense (male, 79.2%; female, 67.4%) mutations versus mild missense (male, 17.1%; female, 23.1%) and the p.N215S (male, 15.0%; female, 15.6%) mutations (P<0.01). Our analyses show a correlation between the prevalence of ocular changes in Fabry disease and disease severity. Consequently, information on ocular findings and α-galactosidase A gene mutation may help assess the risk for more severe Fabry disease. These observed findings are of notable clinical importance, as Fabry disease is characterized by high clinical course variability and only weak genotype-phenotype correlation at the individual patient level. Further confirmatory studies

  10. Questionnaire about psychology/disease correlation – II

    PubMed Central

    Dragoş, D; Ojog, DG; Tănăsescu, MD

    2011-01-01

    Objective. To further evaluate the adequacy of the items in our questionnaire aimed at unraveling the possible correlations between psychological features and internal disorders. This paper is dedicated to the items exploring the individual’s interaction with other people. Method. The items are divided into several subdomains. For each subdomain, we have calculated the correlations between the items of the respective subdomain (inner associations) and with the items in other subdomains (outer associations) by means of chi square test or Fisher exact test as dictated by statistical reasons. We examined the answers from our first 10192 respondents. Results and conclusions. Many inter-item correlations are the consequence of higher or lesser degrees of synonymy. Those within a given subdomain confirm the adequate allocation of items. Those bridging different subdomains may point either to incorrect assignments, or to semantic inclusion relations. Other results are not explicable by semantic similarity, and probably reveal psychological subtleties, such as: most individuals have a sense of undeservedness when badly treated by other people; those easily hurt by insults and humiliations have a propensity to timidity and/or emotivity; the subjects who shun conflicts are more prone to persistent thoughts, brooding people are more sensitive and more prone to conflicts, injustice-indignant people frequently get into conflict although they declare to be bothered by dissent etc. But at the heart of all the PFs in the Interaction-with-other-people domain there seems to be the sense of being undervalued, which should probably be the key issue to be addressed by any therapeutic interventions for diseases psychoemotionally determined by disturbed interpersonal relationships. Abbreviations: PF = psychological feature; Chisq = chi-square; OdRa = odds ratio; OdRaCL = odds ratio confidence limits; ErrProb = probability of error PMID:22514567

  11. Clinical correlates of depressive symptoms in familial Parkinson's disease.

    PubMed

    Pankratz, Nathan; Marder, Karen S; Halter, Cheryl A; Rudolph, Alice; Shults, Cliff W; Nichols, William C; Foroud, Tatiana

    2008-11-15

    Depression is one of the most common nonmotor complications of Parkinson's disease (PD) and has a major impact on quality of life. Although several clinical factors have been associated with depression in PD, the relationship between depression and stage of illness as well as between depression and degree of disability remains controversial. We have collected clinical data on 1,378 PD cases from 632 families, using the Unified Parkinson's Disease Rating Scale (UPDRS) Parts II (activities of daily living) & III (motor), the Mini-Mental State Exam, the Geriatric Depression Scale (GDS), and the Blessed Functional Activity Scale (Blessed). Analyses were performed using the 840 individuals with verified PD and without evidence of cognitive decline. Logistic regression was used to identify study variables that individually and collectively best predicted the presence of depressive symptoms (GDS >or= 10). After correcting for multiple tests, depressive symptoms were significantly associated with Hoehn and Yahr stage and other clinical measures but not with any genetic variant (parkin, LRRK2, APOE). The Blessed score, education, presence of a first degree relative with signs of depression, and UPDRS Part II were found to best predict depressive symptomatology (R(2) = 0.33; P = 4 x 10(-48)). Contrary to several reports, the results from this large study indicate that stage of illness, motor impairment, and functional disability are strongly correlated with depressive symptoms.

  12. Correlating Photoreceptor Mosaic Structure to Clinical Findings in Stargardt Disease

    PubMed Central

    Razeen, Moataz M.; Cooper, Robert F.; Langlo, Christopher S.; Goldberg, Mara R.; Wilk, Melissa A.; Han, Dennis P.; Connor, Thomas B.; Fishman, Gerald A.; Collison, Frederick T.; Sulai, Yusufu N.; Dubra, Alfredo; Carroll, Joseph; Stepien, Kimberly E.

    2016-01-01

    Purpose To demonstrate a method for correlating photoreceptor mosaic structure with optical coherence tomography (OCT) and microperimetry findings in patients with Stargardt disease. Methods A total of 14 patients with clinically diagnosed Stargardt disease were imaged using confocal and split-detection adaptive optics scanning light ophthalmoscopy. Cone photoreceptors were identified manually in a band along the temporal meridian. Resulting values were compared to a normative database (n = 9) to generate cone density deviation (CDD) maps. Manual measurement of outer nuclear layer plus Henle fiber layer (ONL+HFL) thickness was performed, in addition to determination of the presence of ellipsoid zone (EZ) and interdigitation zone (IZ) bands on OCT. These results, along with microperimetry data, were overlaid with the CDD maps. Results Wide variation in foveal structure and CDD maps was seen within this small group. Disruption of ONL+HFL and/or IZ band was seen in all patients, with EZ band preservation in regions with low cone density in 38% of locations analyzed. Normality of retinal lamellar structure on OCT corresponded with cone density and visual function at 50/78 locations analyzed. Outer retinal tubulations containing photoreceptor-like structures were observed in 3 patients. Conclusions The use of CDD color-coded maps enables direct comparison of cone mosaic local density with other measures of retinal structure and function. Larger normative datasets and improved tools for automation of image alignment are needed. Translational Relevance The approach described facilitates comparison of complex multimodal data sets from patients with inherited retinal degeneration, and can be expanded to incorporate other structural imaging or functional testing. PMID:26981328

  13. Correlation of Cough With Disease Activity and Treatment With Cyclophosphamide in Scleroderma Interstitial Lung Disease

    PubMed Central

    Tseng, Chi-Hong; Li, Ning; Elashoff, Robert M.; Tashkin, Donald P.

    2012-01-01

    Background: Cough is a significant symptom in patients with scleroderma interstitial lung disease (SSc-ILD), affecting 73% of the 158 patients enrolled in the Scleroderma Lung Study (SLS), a multicenter randomized trial of oral cyclophosphamide (CYC) vs placebo (PLA) in patients with active interstitial lung disease. Methods: We examined the correlation of cough frequency and severity and phlegm production at baseline in 156 SLS participants with other baseline variables representing SSc-ILD disease activity and the cough response to 1 year of treatment with CYC vs PLA. Results: Patients with cough at baseline had significantly lower diffusing capacity of the lung for carbon monoxide, dyspnea, the quality-of-life physical component summary, and the maximal fibrosis score on high-resolution CT imaging compared with those without cough at baseline. Cough severity and frequency correlated with FVC % predicted. After 12 months of treatment, cough frequency decreased in the CYC group compared with the PLA group and was significantly different from the PLA group at 18 months (6 months after discontinuation of CYC). However, the decreases in cough frequency did not correlate with the changes in FVC or diffusing capacity of the lung for carbon monoxide observed in the CYC group. Treatment-related improvements in cough frequency, as well as in FVC, were no longer apparent 12 months after discontinuation of CYC. Conclusions: Cough is a common symptom in SSc-ILD and correlates with the extent of fibrosis. Cough frequency decreases significantly in response to treatment with CYC but returns to baseline 1 year after withdrawal of treatment. Cough may be a symptom of ongoing fibrosis and an independent variable in assessing therapeutic response to CYC. Trial registry: ClinicalTrials.gov; No.: NCT000004563; URL: www.clinicaltrials.gov PMID:22156609

  14. [A possible correlation between periodontitis and ischaemic heart disease].

    PubMed

    Hansen, Gorm Mørk; Holmstrup, Palle; Tolker-Nielsen, Tim; Køllgaard, Tania; Nielsen, Claus Henrik; Givskov, Michael; Hansen, Peter Riis

    2014-04-28

    Periodontitis is a prevalent chronic inflammatory disease induced by bacterial biofilm in the dental pocket resulting in destruction of the periodontal tissues. Periodontitis is associated with ischaemic heart disease and we here provide a summary of the current evidence linking these two disorders.

  15. Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes

    PubMed Central

    de Bie, P; Muller, P; Wijmenga, C; Klomp, L W J

    2007-01-01

    The trace metal copper is essential for a variety of biological processes, but extremely toxic when present in excessive amounts. Therefore, concentrations of this metal in the body are kept under tight control. Central regulators of cellular copper metabolism are the copper‐transporting P‐type ATPases ATP7A and ATP7B. Mutations in ATP7A or ATP7B disrupt the homeostatic copper balance, resulting in copper deficiency (Menkes disease) or copper overload (Wilson disease), respectively. ATP7A and ATP7B exert their functions in copper transport through a variety of interdependent mechanisms and regulatory events, including their catalytic ATPase activity, copper‐induced trafficking, post‐translational modifications and protein–protein interactions. This paper reviews the extensive efforts that have been undertaken over the past few years to dissect and characterise these mechanisms, and how these are affected in Menkes and Wilson disease. As both disorders are characterised by an extensive clinical heterogeneity, we will discus how the underlying genetic defects correlate with the molecular functions of ATP7A and ATP7B and with the clinical expression of these disorders. PMID:17717039

  16. [Possible correlations of Berger's disease and Schonlein-Henoch purpura].

    PubMed

    Maffei, S; Stefanelli, M; Germini, G; Bragetti, P; Riommi, R; Cesarini, A R; Rufini, S; Castellucci, G

    1989-01-01

    A case of IgA nephropathy is described. The patient had only an attack of Henoch-Schonlein purpura without renal involvement when she was 7 years old. After 6 years of normal urinalysis she developed repeated bouts of gross hematuria and proteinuria. In renal biopsy typical features of Berger's disease were found. This particular case permits to debate whether the two diseases suffered by our patient were related or quite different.

  17. MR Enterography of Inflammatory Bowel Disease with Endoscopic Correlation.

    PubMed

    Kaushal, Pankaj; Somwaru, Alexander S; Charabaty, Aline; Levy, Angela D

    2017-01-01

    Crohn disease (CD) and ulcerative colitis (UC) are the two main forms of idiopathic inflammatory bowel disease (IBD). CD is a transmural chronic inflammatory disorder that can affect any part of the gastrointestinal tract in a discontinuous distribution. UC is a mucosal and submucosal chronic inflammatory disease that typically originates in the rectum and may extend proximally in a continuous manner. In treating patients with CD and UC, clinicians rely heavily on accurate diagnoses and disease staging. Magnetic resonance (MR) enterography used in conjunction with endoscopy and histopathologic analysis can help accurately diagnose and manage disease in the majority of patients. Endoscopy is more sensitive for detection of the early-manifesting mucosal abnormalities seen with IBD and enables histopathologic sampling. MR enterography yields more insightful information about the pathologic changes seen deep to the mucosal layer of the gastrointestinal tract wall and to those portions of the small bowel that are not accessible endoscopically. CD can be classified into active inflammatory, fistulizing and perforating, fibrostenotic, and reparative and regenerative phases of disease. Although CD has a progressive course, there is no stepwise progression between these disease phases, and various phases may exist at the same time. The endoscopic and MR enterographic features of UC can be broadly divided into two categories: acute phase and subacute-chronic phase. Understanding the endoscopic features of IBD and the pathologic processes that cause the MR enterographic findings of IBD can help improve the accuracy of disease characterization and thus optimize the medication and surgical therapies for these patients. (©)RSNA, 2016.

  18. Cerebral correlates of psychotic syndromes in neurodegenerative diseases

    PubMed Central

    Jellinger, Kurt A

    2012-01-01

    Abstract Psychosis has been recognized as a common feature in neurodegenerative diseases and a core feature of dementia that worsens most clinical courses. It includes hallucinations, delusions including paranoia, aggressive behaviour, apathy and other psychotic phenomena that occur in a wide range of degenerative disorders including Alzheimer’s disease, synucleinopathies (Parkinson’s disease, dementia with Lewy bodies), Huntington’s disease, frontotemporal degenerations, motoneuron and prion diseases. Many of these psychiatric manifestations may be early expressions of cognitive impairment, but often there is a dissociation between psychotic/behavioural symptoms and the rather linear decline in cognitive function, suggesting independent pathophysiological mechanisms. Strictly neuropathological explanations are likely to be insufficient to explain them, and a large group of heterogeneous factors (environmental, neurochemical changes, genetic factors, etc.) may influence their pathogenesis. Clinico-pathological evaluation of behavioural and psychotic symptoms (PS) in the setting of neurodegenerative and dementing disorders presents a significant challenge for modern neurosciences. Recognition and understanding of these manifestations may lead to the development of more effective preventive and therapeutic options that can serve to delay long-term progression of these devastating disorders and improve the patients’ quality of life. A better understanding of the pathophysiology and distinctive pathological features underlying the development of PS in neurodegenerative diseases may provide important insights into psychotic processes in general. PMID:21418522

  19. Clinical and radiological correlations in patients with gestational trophoblastic disease*

    PubMed Central

    Lima, Lana de Lourdes Aguiar; Parente, Raphael Câmara Medeiros; Maestá, Izildinha; Amim Junior, Joffre; de Rezende Filho, Jorge Fonte; Montenegro, Carlos Antonio Barbosa; Braga, Antônio

    2016-01-01

    Gestational trophoblastic disease is an abnormality of pregnancy that encompasses a group of diseases that differ from each other in their propensity for regression, invasion, metastasis, and recurrence. In the past, it was common for patients with molar pregnancy to present with marked symptoms: copious bleeding; theca lutein cysts; uterus larger than appropriate for gestational age; early preeclampsia; hyperemesis gravidarum; and hyperthyroidism. Currently, with early diagnosis made by ultrasound, most patients are diagnosed while the disease is still in the asymptomatic phase. In cases of progression to trophoblastic neoplasia, staging-typically with Doppler flow studies of the pelvis and chest X-ray, although occasionally with computed tomography or magnetic resonance imaging-is critical to the choice of an appropriate antineoplastic therapy regimen. Because it is an unusual and serious disease that affects women of reproductive age, as well as because its appropriate treatment results in high cure rates, it is crucial that radiologists be familiar with gestational trophoblastic disease, in order to facilitate its early diagnosis and to ensure appropriate follow-up imaging. PMID:27777478

  20. Linguistic Correlates of Asymmetric Motor Symptom Severity in Parkinson's Disease

    ERIC Educational Resources Information Center

    Holtgraves, Thomas; McNamara, Patrick; Cappaert, Kevin; Durso, Raymond

    2010-01-01

    Asymmetric motor severity is common in Parkinson's Disease (PD) and provides a method for examining the neurobiologic mechanisms underlying cognitive and linguistic deficits associated with the disorder. In the present research, PD participants (N = 31) were assessed in terms of the asymmetry of their motor symptoms. Interviews with the…

  1. An Examination of the Demographic and Environmental Variables Correlated with Lyme Disease Emergence in Virginia.

    PubMed

    Seukep, Sara E; Kolivras, Korine N; Hong, Yili; Li, Jie; Prisley, Stephen P; Campbell, James B; Gaines, David N; Dymond, Randel L

    2015-12-01

    Lyme disease is the United States' most significant vector-borne illness. Virginia, on the southern edge of the disease's currently expanding range, has experienced an increase in Lyme disease both spatially and temporally, with steadily increasing rates over the past decade and disease spread from the northern to the southwestern part of the state. This study used a Geographic Information System and a spatial Poisson regression model to examine correlations between demographic and land cover variables, and human Lyme disease from 2006 to 2010 in Virginia. Analysis indicated that herbaceous land cover is positively correlated with Lyme disease incidence rates. Areas with greater interspersion between herbaceous and forested land were also positively correlated with incidence rates. In addition, income and age were positively correlated with incidence rates. Levels of development, interspersion of herbaceous and developed land, and population density were negatively correlated with incidence rates. Abundance of forest fragments less than 2 hectares in area was not significantly correlated. Our results support some findings of previous studies on ecological variables and Lyme disease in endemic areas, but other results have not been found in previous studies, highlighting the potential contribution of new variables as Lyme disease continues to emerge southward.

  2. Celiac Disease and Myointimal Proliferation: A Possible Correlation?

    PubMed Central

    Merra, Giuseppe; Lago, Antonio Dal; Roccarina, Davide; Gasbarrini, Giovanni; Gasbarrini, Antonio; Ghirlanda, Giovanni

    2008-01-01

    Celiac disease (CD) is an autoimmune disorder of the small bowel that occurs in genetically predisposed people of all ages, from middle infancy, and is caused by a reaction to gliadin, a gluten protein. Some patients are diagnosed with symptoms related to the decreased absorption of nutrients or with various symptoms which, although statistically linked, have no clear relationship with the malfunctioning bowel. Classic symptoms of CD include diarrhea, weight loss, and fatigue; bowel symptoms may be limited or even absent. In this article we describe the case of a young woman with CD who presents with myointimal proliferation. However multiple cases of vessel thrombosis have been reported in patients with CD. Despite the fact that no definitive relationship between these diseases could be explained, we think this association must be remembered especially in cases of young and tenuous women with these vascular abnormalities. PMID:21897789

  3. Cerebral correlates of psychotic symptoms in Alzheimer's disease

    PubMed Central

    Mega, M.; Lee, L.; Dinov, I.; Mishkin, F.; Toga, A.; Cummings, J.

    2000-01-01

    BACKGROUND—Psychotic symptoms are produced by distributed neuronal dysfunction. Abnormalities of reality testing and false inference implicate frontal lobe abnormalities.
OBJECTIVES—To identify the functional imaging profile of patients with Alzheimer's disease manifesting psychotic symptoms as measured by single photon emission computed tomography (SPECT).
METHODS—Twenty patients with Alzheimer's disease who had SPECT and clinical evaluations were divided into two equal groups with similar mini mental status examination (MMSE), age, sex, and the range of behaviours documented by the neuropsychiatric inventory (NPI), except delusions and hallucinations. SPECT studies, registered to a probabilistic anatomical atlas, were normalised across the combined group mean intensity level, and subjected to a voxel by voxel subtraction of the non-psychotic minus psychotic groups. Subvolume thresholding (SVT) corrected random lobar noise to produce a three dimensional functional significance map.
RESULTS—The significance map showed lower regional perfusion in the right and left dorsolateral frontal, left anterior cingulate, and left ventral striatal regions along with the left pulvinar and dorsolateral parietal cortex, in the psychotic versus non-psychotic group.
CONCLUSION—Patients with Alzheimer's disease who manifest psychosis may have disproportionate dysfunction of frontal lobes and related subcortical and parietal structures.

 PMID:10896687

  4. Podoplanin Expression Correlates with Disease Progression in Mycosis Fungoides.

    PubMed

    Jankowska-Konsur, Alina; Kobierzycki, Christopher; Grzegrzółka, Jędrzej; Piotrowska, Aleksandra; Gomulkiewicz, Agnieszka; Glatzel-Plucinska, Natalia; Reich, Adam; Podhorska-Okołów, Marzenna; Dzięgiel, Piotr; Szepietowski, Jacek C

    2017-02-08

    The aim of this study was to investigate the role of lymphangiogenesis in the clinical progression and outcome of mycosis fungoides. Immunohistochemistry and Western blot techniques were used to assess the expression of podoplanin and vascular endothelial growth factor C in mycosis fungoides. Expression of vascular endothelial growth factor C measured by immunohistochemistry was significantly higher in mycosis fungoides samples in comparison with control cases (chronic benign dermatoses) (p = 0.0012). Increased expression of podoplanin was found in advanced vs. early mycosis fungoides (p < 0.0001), and was positively correlated with cutaneous and nodal involvement (p < 0.001, p < 0.0001; respectively). Higher podoplanin expression was also significantly associated with shorter survival (p < 0.001). Strong positive correlation was observed between expression of podoplanin analysed by immunohistochemistry and Western blot (r = 0.75, p < 0.0001). A similar association was shown regarding expression of vascular endothelial growth factor C (r = 0.68, p = 0.0007). In conclusion, these results suggest that increased expression of podoplanin is associated with poor clinical course, as well as shorter survival, of patients with mycosis fungoides.

  5. Disease-induced variability of genetic correlations: ascites in broilers as a case study.

    PubMed

    de Greef, K H; Janss, L L; Vereijken, A L; Pit, R; Gerritsen, C L

    2001-07-01

    Breeding against a production disease is complicated by multiple relationships between productivity, disease, and environment. Ascites in broilers is such a disease. The combination of the reasonably well understood etiology (a physiological/pathological cascade due to inadequate oxygen supply) and the practical relevance makes ascites a relevant case for demonstrating and partly revealing these complex relationships. Chickens (n = 2,788) were tested in an ascites-challenging (cold) environment. Genetic analysis of mortality and pathology in combination with performance and physiological traits (especially blood gas traits) revealed ample opportunities for selection against ascites expression. The genetic correlation structure indicated that different mortality traits and pathology traits roughly represent one common characteristic. Direct selection against pathology is more effective than selection on the basis of growth or blood gas traits. The observed negative correlation (-0.26) between productivity and ascites was unexpected. From the etiology of ascites (inadequate supply of oxygen relative to the demand), a positive (unfavorable) correlation was expected. To demonstrate that the actual disease occurrence caused this apparent contradiction, the data from the undiseased subpopulation were reanalyzed. In the undiseased subpopulation, the genetic correlation between productivity and ascites was positive (0.29). This discrepancy was confirmed by comparing regression of ascites expression on actual performance with regression of ascites on independently assessed performance breeding values. The lability of the genetic correlation was explained from complex interactions between productivity, disease susceptibility, and actual occurrence of the disease. The revealed mechanism can be generalized to other production-related diseases and results in systematically lower genetic correlations between disease and productivity. It was inferred that genetic correlations

  6. Pilot study of correlation of pulp stones with cardiovascular disease.

    PubMed

    Edds, A C; Walden, J E; Scheetz, J P; Goldsmith, L J; Drisko, C L; Eleazer, P D

    2005-07-01

    We propose that calcification of dental pulp may have a similar pathogenesis as calcified atheromas and could lead to use of routine dental radiographs as a rapid screening method for early identification of potential cardiovascular disease (CVD). Fifty-five dental patients ages 20 to 55 were chosen because pulp stones in pulpally noninflamed teeth were not expected in this age group. They completed a questionnaire regarding their CVD status and that of their parents and siblings. Entry criteria included at least one asymptomatic, minimally restored, noncarious molar and no history of gout, renal disease, or renal lithiasis. Patients' periapical radiographs of record were viewed to determine the presence of pulp stones. There was a significant relationship between pre-existing CVD and pulp stones (odds ratio of 4.4 with a 95% confidence interval of 1.1, 18.7), but no relationship was found for family history of CVD and pulp stones (odds ratio of 1.7 with a 95% confidence interval of 0.5, 5.5). Seventy-four percent (14/19) of patients with reported CVD had detectable pulp stones while only 39% (14/36) of patients without a history of CVD had pulp stones. This pilot study demonstrates that patients with CVD have an increased incidence of pulp stones in teeth with noninflamed pulps compared to patients with no history of CVD. No relationship was found between presence of pulp stones and family history of CVD. The findings suggest that dental radiographic determination of the presence or absence of pulp stones may have possibilities for use in CVD screening.

  7. Neuroimaging correlates of cognitive impairment and dementia in Parkinson's disease.

    PubMed

    Mak, Elijah; Su, Li; Williams, Guy B; O'Brien, John T

    2015-08-01

    There has been a gradual shift in the definition of Parkinson's disease, from a movement disorder to a neurodegenerative condition affecting multiple cognitive domains. Mild cognitive impairment (PD-MCI) is a frequent comorbidity in PD that is associated with progression to dementia (PDD) and debilitating consequences for patients and caregivers. At present, the pathophysiology underpinning cognitive impairment in PD is not established, although emerging evidence has suggested that multi-modal imaging biomarkers could be useful in the early diagnosis of PD-MCI and PDD, thereby identifying at-risk patients to enable treatment at the earliest stage possible. Structural MRI studies have revealed prominent grey matter atrophy and disruptions of white matter tracts in PDD, although findings in non-demented PD have been more variable. There is a need for further longitudinal studies to clarify the spatial and temporal progression of morphological changes in PD, as well as to assess their underlying involvement in the evolution of cognitive deficits. In this review, we discuss the aetiology and neuropsychological profiles of PD-MCI and PDD, summarize the putative imaging substrates in light of evidence from multi-modal neuroimaging studies, highlight limitations in the present literature, and suggest recommendations for future research.

  8. Examination of the Spatial Correlation of Statistics Information in the Ultrasonic Echo from Diseased Liver

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Tadashi; Hachiya, Hiroyuki; Kamiyama, Naohisa; Moriyasu, Fuminori

    2002-05-01

    To realize a quantitative diagnosis of liver cirrhosis, we have been analyzing the characteristics of echo amplitude in B-mode images. Realizing the distinction between liver diseases such as liver cirrhosis and chronic hepatitis is required in the field of medical ultrasonics. In this study, we examine the spatial correlation, with the coefficient of correlation between the frames and the amplitude characteristics of each frame, using the volumetric data of RF echo signals from normal and diseased liver. It is found that there is a relationship between the tissue structure of liver and the spatial correlation of echo information.

  9. Serum microRNA-125a-5p, a useful biomarker in liver diseases, correlates with disease progression.

    PubMed

    Zheng, Jianjian; Zhou, Zhenxu; Xu, Ziqiang; Li, Guojun; Dong, Peihong; Chen, Zhanguo; Lin, Dezhao; Chen, Bicheng; Yu, Fujun

    2015-07-01

    It has been demonstrated that liver microRNA-125a-5p (miR-125a-5p) is correlated with disease progression in different liver diseases, including liver fibrosis and hepatocellular carcinoma (HCC). The present study investigated whether serum miR-125a-5p correlated with the progression of different liver diseases. Serum samples were obtained from healthy individuals, patients with chronic hepatitis B who had undergone a liver biopsy, and patients with HCC and were analyzed for the levels of miR-125a-5p. Compared with the healthy controls, the serum levels of miR-125a-5p were significantly higher in the liver fibrosis serum, and were reduced in HCC. With the development of liver fibrosis, there was a significant increase in the expression of miR-125a-5p (P<0.05). In comparing histological activity index (HAI) scores, higher expression levels of miR125a-5p were observed in the high HAI score group (P<0.05). Furthermore, correlation between serum miR-125a-5p and viral replication (P<0.001) was observed. Notably, miR-125a-5p demonstrated significant correlation with other markers in the liver fibrosis group (P<0.001). In the patients with HCC, lower serum levels of miR-125a-5p were correlated with a poor prognosis, determined by Kaplan-Meier curve analysis (P=0.009). In the liver fibrosis and HCC groups, different expression levels of serum miR-125a-5p were observed, and were correlated with disease progression. The results of the present study suggested that serum miR-125a-5p may be used as a non-invasive biomarker for monitoring disease progression in liver diseases.

  10. No Geographic Correlation between Lyme Disease and Death Due to 4 Neurodegenerative Disorders, United States, 2001-2010.

    PubMed

    Forrester, Joseph D; Kugeler, Kiersten J; Perea, Anna E; Pastula, Daniel M; Mead, Paul S

    2015-11-01

    Associations between Lyme disease and certain neurodegenerative diseases have been proposed, but supportive evidence for an association is lacking. Similar geographic distributions would be expected if 2 conditions were etiologically linked. Thus, we compared the distribution of Lyme disease cases in the United States with the distributions of deaths due to Alzheimer disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Parkinson disease; no geographic correlations were identified. Lyme disease incidence per US state was not correlated with rates of death due to ALS, MS, or Parkinson disease; however, an inverse correlation was detected between Lyme disease and Alzheimer disease. The absence of a positive correlation between the geographic distribution of Lyme disease and the distribution of deaths due to Alzheimer disease, ALS, MS, and Parkinson disease provides further evidence that Lyme disease is not associated with the development of these neurodegenerative conditions.

  11. Does APO ε4 correlate with MRI changes in Alzheimer's disease?

    PubMed Central

    Doody, R; Azher, S; Haykal, H; Dunn, J; Liao, T; Schneider, L

    2000-01-01

    OBJECTIVE—To assess the relation between APO E genotype and MRI white matter changes in Alzheimer's disease. The APO ε4 allele is correlated with amyloid angiopathy and other neuropathologies in Alzheimer's disease and could be associated with white matter changes. If so, there should be a dose effect.
METHODS—104 patients with probable Alzheimer's disease (NINCDS-ADRDA criteria) in this Alzheimer's Disease Research Centre were studied. Patients received MRI and APO E genotyping by standardised protocols. Axial MRI was scored (modified Schelten's scale) for the presence and degree of white matter changes and atrophy in several regions by a neuroradiologist blinded to genotype. Total white matter and total atrophy scores were also generated. Data analysis included Pearson's correlation for regional and total imaging scores and analysis of variance (ANOVA) (or Kruskal-Wallis) and χ2 for demographic and disease related variables.
RESULTS—30 patients had no ε4, 53 patients were heterozygous, and 21 patients were homozygous. The three groups did not differ in sex distribution, age of onset, age at MRI, MMSE, clinical dementia rating, or modified Hachinski ischaemia scores. There were no significant correlations between total or regional white matter scores and APO E genotype (Pearson correlation).
CONCLUSIONS—No correlation between total or regional white matter scores and APO E genotype was found. The pathogenesis of white matter changes in Alzheimer's disease may be independent of APO E genotype.

 PMID:11032626

  12. Altered fractal dynamics of gait: reduced stride-interval correlations with aging and Huntington's disease

    NASA Technical Reports Server (NTRS)

    Hausdorff, J. M.; Mitchell, S. L.; Firtion, R.; Peng, C. K.; Cudkowicz, M. E.; Wei, J. Y.; Goldberger, A. L.

    1997-01-01

    Fluctuations in the duration of the gait cycle (the stride interval) display fractal dynamics and long-range correlations in healthy young adults. We hypothesized that these stride-interval correlations would be altered by changes in neurological function associated with aging and certain disease states. To test this hypothesis, we compared the stride-interval time series of 1) healthy elderly subjects and young controls and of 2) subjects with Huntington's disease and healthy controls. Using detrended fluctuation analysis we computed alpha, a measure of the degree to which one stride interval is correlated with previous and subsequent intervals over different time scales. The scaling exponent alpha was significantly lower in elderly subjects compared with young subjects (elderly: 0.68 +/- 0.14; young: 0.87 +/- 0.15; P < 0.003). The scaling exponent alpha was also smaller in the subjects with Huntington's disease compared with disease-free controls (Huntington's disease: 0.60 +/- 0.24; controls: 0.88 +/-0.17; P < 0.005). Moreover, alpha was linearly related to degree of functional impairment in subjects with Huntington's disease (r = 0.78, P < 0.0005). These findings demonstrate that strike-interval fluctuations are more random (i.e., less correlated) in elderly subjects and in subjects with Huntington's disease. Abnormal alterations in the fractal properties of gait dynamics are apparently associated with changes in central nervous system control.

  13. Quantitative EEG parameters correlate with the progression of human prion diseases

    PubMed Central

    Wehner, Tim; Lowe, Jessica; Porter, Marie-Claire; Kenny, Joanna; Thompson, Andrew; Rudge, Peter; Collinge, John; Mead, Simon

    2016-01-01

    Background Prion diseases are universally fatal and often rapidly progressive neurodegenerative diseases. EEG has long been used in the diagnosis of sporadic Creutzfeldt-Jakob disease; however, the characteristic waveforms do not occur in all types of prion diseases. Here, we re-evaluate the utility of EEG by focusing on the development of biomarkers. We test whether abnormal quantitative EEG parameters can be used to measure disease progression in prion diseases or predict disease onset in healthy individuals at risk of disease. Methods In the National Prion Monitoring Cohort study, we did quantitative encephalography on 301 occasions in 29 healthy controls and 67 patients with prion disease. The patients had either inherited prion disease or sporadic Creutzfeldt-Jakob disease. We computed the main background frequency, the α and θ power and the α/θ power ratio, then averaged these within 5 electrode groups. These measurements were then compared among participant groups and correlated with functional and cognitive scores cross-sectionally and longitudinally. Results We found lower main background frequency, α power and α/θ power ratio and higher θ power in patients compared to control participants. The main background frequency, the power in the α band and the α/θ power ratio also differed in a consistent way among the patient groups. Moreover, the main background frequency and the α/θ power ratio correlated significantly with functional and cognitive scores. Longitudinally, change in these parameters also showed significant correlation with the change in clinical and cognitive scores. Conclusions Our findings support the use of quantitative EEG to follow the progression of prion disease, with potential to help evaluate the treatment effects in future clinical-trials. PMID:27413165

  14. A scientific correlation between dystemprament in Unani medicine and diseases: a systematic review

    PubMed Central

    Miraj, Sepideh; Kiani, Sara

    2016-01-01

    Background Temperament or mezaj refers to four different humors differentiating in individuals and, as a result, proposes specific therapy for their diseases. Objective The aim of this study was to overview the scientific correlation between temperaments in Unani medicine and diseases. Methods This study was carried out from March 2015 to February 2016. A computerized search of published articles was performed using PubMed, Google Scholar, Scopus and Web of Science, and Medline databases as well as local and regional resources between 1983 and 2014. The search terms used were temperament, dystemprament, diseases, mizaj, sue mizaj. Additional sources were identified through cross-referencing. Results The result of this study indicated the relationship between dystemprament and incidence of some diseases such as muscle diseases, skin diseases, asthma, palpitation, bipolar disorder, hemodialysis hysteria, hypertension, sinusitis, aging, diabetes, diarrhea. However, further studies are needed to prove the role of dystemprament in incidence of other diseases. Conclusion The result of this study indicated the relationship between dystemprament and incidence of some disease such as muscle diseases, skin diseases, asthma, palpitation, bipolar disorder, hemodialysis hysteria, hypertension, sinusitis, aging, diabetes, diarrhea. These results are helpful for patients and physicians to change humors toward equilibrium to avoid diseases. Further studies are required to discover the relationship between dystemprament and other diseases. PMID:28070258

  15. High Interleukin 17 Expression Is Correlated With Better Cardiac Function in Human Chagas Disease

    PubMed Central

    Magalhães, Luisa M. D.; Villani, Fernanda N. A.; Nunes, Maria do Carmo P.; Gollob, Kenneth J.; Rocha, Manoel O. C.; Dutra, Walderez O.

    2013-01-01

    This study was designed to investigate whether the expression of interleukin 17 (IL-17) is associated with the indeterminate or cardiac clinical forms of Chagas disease and whether IL-17 expression can be correlated with patients' cardiac function. Our results demonstrated that cardiac Chagas patients have a lower intensity of expression of IL-17 by total lymphocytes and lower frequency of circulating T helper 17 cells. Correlative analysis showed that high IL-17 expression was associated with better cardiac function, as determined by left ventricular ejection fraction and left ventricular diastolic diameter values. Therefore, IL-17 expression can be a protective factor to prevent myocardial damage in human Chagas disease. PMID:23204182

  16. Correlation between ankle brachial index and coronary artery disease severity in elderly Egyptians.

    PubMed

    Amer, Moatasem S; Tawfik, Heba Mohamed; Elmoteleb, Ayman M Abd; Maamoun, Manar M A

    2014-11-01

    We investigated the association between ankle brachial index (ABI) and coronary heart disease (CHD) severity in elderly Egyptians using different measures. We conducted a case-control study from November 2010 to June 2012 including 200 male and female patients with ischemia≥60 years who were divided into 100 cases and 100 controls according to ABI and redivided according to age. They underwent coronary angiography followed by ABI measurement using a hand-held Doppler. The CHD severity was estimated using the SYNTAX and Jeopardy scores and number of diseased vessels, which increased significantly in patients with peripheral artery disease (P<.001) for all. All 3 measures had strong negative correlation with ABI (P≤.001 for Jeopardy, <.001 for SYNTAX scores, and .004 for number of diseased vessels) and were correlated with each other. We concluded that ABI can reflect CHD severity in elderly Egyptians.

  17. Calprotectin in gingival crevicular fluid correlates with clinical and biochemical markers of periodontal disease.

    PubMed

    Kido, J; Nakamura, T; Kido, R; Ohishi, K; Yamauchi, N; Kataoka, M; Nagata, T

    1999-10-01

    Clinical and biochemical markers of periodontal disease have been used for precise objective diagnosis of periodontal inflammation. Interleukin 1beta (IL-1beta) and prostaglandin E2 (PGE2), inflammatory factors, levels in gingival crevicular fluid (GCF) of patients with periodontal disease are elevated and have been studied as biochemical markers. The levels of calprotectin, a leukocyte protein, in body fluids of patients with some inflammatory diseases are raised. Recently, we detected calprotectin in GCF and its concentrations in periodontal pockets were higher than those in healthy gingival crevices. In this study, we investigated the correlations between GCF calprotectin levels and clinical indicators (probing depth and bleeding on probing, BOP), and the IL-1beta or PGE2 levels in GCE Probing depth and BOP at 130 sites of 110 subjects with periodontal or other oral diseases were examined, then GCF samples were collected and their calprotectin, IL-1beta and PGE2 were determined by ELISA. The calprotectin level correlated positively with the probing depth and was significantly higher at BOP-positive than BOP-negative sites. There were significant, positive correlations between the calprotectin and IL-1beta or PGE2 concentrations. These results indicate that the calprotectin level in GCF correlates well with clinical and biochemical markers of periodontal disease and suggest that calprotectin may be useful for evaluating the extent of periodontal inflammation.

  18. Specificity of immunoglobulin E in coccidioidomycosis and correlation with disease involvement.

    PubMed Central

    Cox, R A; Baker, B S; Stevens, D A

    1982-01-01

    Serum immunoglobulin E (IgE) antibodies were quantitated in 26 patients with active pulmonary coccidioidomycosis, 59 patients with active disseminated disease, 12 patients in clinical remission, and 91 healthy subjects. Significant differences were obtained in IgE serum levels of patients with active disease versus healthy subjects (P less than 0.0001). Patients with pulmonary coccidioidomycosis did not differ in their IgE levels when compared with patients with disseminated disease. However, serum IgE levels were significantly increased in patients with disease involving two or more organ systems when compared with patients with pulmonary disease or extrapulmonary disease involving a single organ system (P less than 0.02). Total serum IgE correlated with anti-Coccidioides IgE (P less than 0.001), but with only six exceptions, patients with anti-Coccidioides IgE also exhibited IgE antibodies to 1 or more of 12 common allergens. The correlation between hyperproduction of IgE and disease severity coupled with the depressed cell-mediated immune status of patients with this disease suggests a defect(s) in the T-lymphocyte population which functions to regulate IgE synthesis. PMID:7118252

  19. Neuroanatomical Correlates of Recognizing Face Expressions in Mild Stages of Alzheimer's Disease.

    PubMed

    Sapey-Triomphe, Laurie-Anne; Heckemann, Rolf A; Boublay, Nawele; Dorey, Jean-Michel; Hénaff, Marie-Anne; Rouch, Isabelle; Padovan, Catherine; Hammers, Alexander; Krolak-Salmon, Pierre

    2015-01-01

    Early Alzheimer's disease can involve social disinvestment, possibly as a consequence of impairment of nonverbal communication skills. This study explores whether patients with Alzheimer's disease at the mild cognitive impairment or mild dementia stage have impaired recognition of emotions in facial expressions, and describes neuroanatomical correlates of emotion processing impairment. As part of the ongoing PACO study (personality, Alzheimer's disease and behaviour), 39 patients with Alzheimer's disease at the mild cognitive impairment or mild dementia stage and 39 matched controls completed tests involving discrimination of four basic emotions-happiness, fear, anger, and disgust-on photographs of faces. In patients, automatic volumetry of 83 brain regions was performed on structural magnetic resonance images using MAPER (multi-atlas propagation with enhanced registration). From the literature, we identified for each of the four basic emotions one brain region thought to be primarily associated with the function of recognizing that emotion. We hypothesized that the volume of each of these regions would be correlated with subjects' performance in recognizing the associated emotion. Patients showed deficits of basic emotion recognition, and these impairments were correlated with the volumes of the expected regions of interest. Unexpectedly, most of these correlations were negative: better emotional facial recognition was associated with lower brain volume. In particular, recognition of fear was negatively correlated with the volume of amygdala, disgust with pallidum, and happiness with fusiform gyrus. Recognition impairment in mild stages of Alzheimer's disease for a given emotion was thus associated with less visible atrophy of functionally responsible brain structures within the patient group. Possible explanations for this counterintuitive result include neuroinflammation, regional β-amyloid deposition, or transient overcompensation during early stages of

  20. Kawasaki disease and the emerging coronary artery disease epidemic in India: is there a correlation?

    PubMed

    Singh, Surjit; Aulakh, Roosy; Kawasaki, Tomisaku

    2014-04-01

    Although Kawasaki disease (KD) is now being increasingly reported from India, the vast majority of children with KD are still not being diagnosed and treated. A recent study from Chandigarh has shown that the incidence of KD is at least 4.54/100,000 children below 15 y of age. Extrapolations of this figure suggest that a minimum of 17,417 new cases of KD would be occurring every year in our country. A significant proportion of these children may develop coronary artery abnormalities. These children would then be at risk of developing myocardial ischemia as young adults. It is authors' contention that (undiagnosed) KD in childhood may be contributing to the growing pool of coronary artery disease (CAD) in India. Similarly, a missed diagnosis of KD in childhood should be considered as a possibility while evaluating adults with CAD, especially when there are no overt risk factors and no family history of the disease.

  1. Correlation between PABPN1 genotype and disease severity in oculopharyngeal muscular dystrophy

    PubMed Central

    Trollet, Capucine; Stojkovic, Tanya; de Becdelievre, Alix; Perie, Sophie; Pouget, Jean; Eymard, Bruno

    2017-01-01

    Objective: Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant adult-onset disease characterized by progressive ptosis, dysphagia, and proximal limb weakness. The genetic cause is an expanded (GCN)n mutation in the PABPN1 gene encoding for the polyadenylate-binding protein nuclear 1. We hypothesized a potential correlation between the size of the (GCN)n expansion and the severity of the phenotype. To do this, we characterized the distribution of the genotypes as well as their correlation with age at diagnosis and phenotypical features in a large cohort of heterozygous and homozygous patients with OPMD in France with a confirmed molecular diagnosis of PABPN1. Methods: We explored 354 unrelated index cases recruited between 1999 and 2014 in several neuromuscular centers in France. Results: This cohort allowed us to characterize the frequency of mutated alleles in the French population and to demonstrate a statistical correlation between the size of the expansion and the mean age at diagnosis. We also confirmed that homozygous patients present with a more severe disease. Conclusions: It has been difficult to establish phenotype–genotype correlations because of the rare nature of this disease. Our work demonstrates that patients with OPMD with longer PABPN1 expansion are on average diagnosed at an earlier age than patients with a shorter expansion, confirming that polyalanine expansion size plays a role in OPMD, with an effect on disease severity and progression. PMID:28011929

  2. Correlation between calcium and phosphate levels to calculus accumulation on coronary heart disease patients

    NASA Astrophysics Data System (ADS)

    Cahaya, Cindy; Masulili, Sri Lelyati C.; Lessang, Robert; Radi, Basuni

    2017-02-01

    Coronary Artery Disease (CAD) or Coronary Heart Disease (CHD) is a disease that happened because of blood flow being blocked by atherosclerosis. Atherosclerosis is a process of hardening of the arteries which characterized by thickening and loss of elasticity of the intimal layer of vascular wall, by lipid deposit. Periodontitis is a chronic multifactorial inflammatory disease caused by microorganism and characterized by progressive destruction of the tooth supporting apparatus leading to tooth loss. Many studies use saliva as a valuable source for clinically information, as an asset for early diagnosis, prognostic and reviewer for pascatherapy status. Dental calculus had happened as a consequence of saliva supersaturation by calcium and phosphate. Salivary flow rate and its composition influence the formation of calculus. Increasing salivary calcium levels is characteristic of periodontitis patients. An important hipotesis in Cardiology is chronic infections contribute in atherosclerosis. Objective: To analyse the correlation between calcium and phosphate levels in saliva to calculus accumulation on CHD patients. Result: Correlation analysis between salivary calcium levels with calculus accumulation in patients with CHD and non-CHD showed no significant p value, p=0.59 and p=0.518. Correlation analysis between salivary phosphate levels and calculus accumulation showed no significant p value, p=0.836 for CHD patients and p=0.484 for non-CHD patients. Conclusion: There are no correlation between calcium levels and phosphate levels with calculus accumulation in CHD patients. Further research need to be done.

  3. Synchrotron radiation analysis of possible correlations between metal status in human cementum and periodontal disease

    SciTech Connect

    Martin, R.R.; Naftel, S.J.; Nelson, A.J.; Edwards, M.; Mithoowani, H.; Stakiw, J.

    2010-03-16

    Periodontitis is a serious disease that affects up to 50% of an adult population. It is a chronic condition involving inflammation of the periodontal ligament and associated tissues leading to eventual tooth loss. Some evidence suggests that trace metals, especially zinc and copper, may be involved in the onset and severity of periodontitis. Thus we have used synchrotron X-ray fluorescence imaging on cross sections of diseased and healthy teeth using a microbeam to explore the distribution of trace metals in cementum and adhering plaque. The comparison between diseased and healthy teeth indicates that there are elevated levels of zinc, copper and nickel in diseased teeth as opposed to healthy teeth. This preliminary correlation between elevated levels of trace metals in the cementum and plaque of diseased teeth suggests that metals may play a role in the progress of periodontitis.

  4. Correlation between erythrocyte sedimentation rate and C-reactive protein level in patients with rheumatic diseases

    PubMed Central

    Kotulska, Anna; Kopeć-Mędrek, Magdalena; Grosicka, Anida; Kubicka, Monika

    2015-01-01

    Objectives Erythrocyte sedimentation rate (ESR) and serum level of C-reactive protein (CRP) are the acute phase reactants most commonly determined in patients with rheumatic diseases. The indices are affected by different factors, but both of them are applied for evaluation of the disease activity in patients with inflammatory disorders of the musculoskeletal system. Material and methods The authors compared the results of ESR and CRP, which were carried out during routine diagnosis in 200 patients admitted to the Department of Rheumatology. Results A significant correlation between ESR and CRP was found (ESR after 1 h/CRP: correlation coefficient 0.6944, ESR after 2 h/CRP: correlation coefficient 0.6126). There was no difference in ESR or CRP between male and female patients, and patients older than 40 years had higher ESR and CRP. Conclusions The obtained results support the usefulness of both indices in the clinical practice of rheumatologists. PMID:27407254

  5. Correlation between hippocampal volumes and medial temporal lobe atrophy in patients with Alzheimer's disease

    PubMed Central

    Dhikav, Vikas; Duraiswamy, Sharmila; Anand, Kuljeet Singh

    2017-01-01

    Introduction: Hippocampus undergoes atrophy in patients with Alzheimer's disease (AD). Calculation of hippocampal volumes can be done by a variety of methods using T1-weighted images of magnetic resonance imaging (MRI) of the brain. Medial temporal lobes atrophy (MTL) can be rated visually using T1-weighted MRI brain images. The present study was done to see if any correlation existed between hippocampal volumes and visual rating scores of the MTL using Scheltens Visual Rating Method. Materials and Methods: We screened 84 subjects presented to the Department of Neurology of a Tertiary Care Hospital and enrolled forty subjects meeting the National Institute of Neurological and Communicative Disorders and Stroke, AD related Disease Association criteria. Selected patients underwent MRI brain and T1-weighted images in a plane perpendicular to long axis of hippocampus were obtained. Hippocampal volumes were calculated manually using a standard protocol. The calculated hippocampal volumes were correlated with Scheltens Visual Rating Method for Rating MTL. A total of 32 cognitively normal age-matched subjects were selected to see the same correlation in the healthy subjects as well. Sensitivity and specificity of both methods was calculated and compared. Results: There was an insignificant correlation between the hippocampal volumes and MTL rating scores in cognitively normal elderly (n = 32; Pearson Correlation coefficient = 0.16, P > 0.05). In the AD Group, there was a moderately strong correlation between measured hippocampal volumes and MTL Rating (Pearson's correlation coefficient = −0.54; P < 0.05. There was a moderately strong correlation between hippocampal volume and Mini-Mental Status Examination in the AD group. Manual delineation was superior compared to the visual method (P < 0.05). Conclusions: Good correlation was present between manual hippocampal volume measurements and MTL scores. Sensitivity and specificity of manual measurement of hippocampus was

  6. CSF tau markers are correlated with hippocampal volume in Alzheimer's disease.

    PubMed

    de Souza, Leonardo C; Chupin, Marie; Lamari, Foudil; Jardel, Claude; Leclercq, Delphine; Colliot, Olivier; Lehéricy, Stéphane; Dubois, Bruno; Sarazin, Marie

    2012-07-01

    Hippocampal atrophy as assessed by magnetic resonance imaging (MRI) and abnormal cerebrospinal fluid (CSF) biomarkers are supportive features for the diagnosis of Alzheimer's disease (AD) and are assumed to be indirect pathological markers of the disease. In AD patients, antemortem MRI hippocampal volumes (HVs) correlate with the density of neurofibrillary tangles (but not with senile plaques) at autopsy suggesting that HVs may better correlate with CSF tau and hyperphosphorylated tau (P-tau) levels than CSF amyloid beta protein (Aβ)(42) level. Here, we tested this hypothesis in a well-defined AD group. Patients were selected according to the New Research Criteria for AD, including specific episodic memory deficit and CSF AD profile (defined as abnormal ratio of Aβ(42):tau). MRI was performed within 6 months of lumbar puncture. HVs were obtained using automated segmentation software. Thirty-six patients were included. Left HV correlated with CSF tau (R = -0.53) and P-tau (R = -0.56) levels. Mean HVs correlated with the CSF P-tau level (R = -0.52). No correlation was found between any brain measurement and CSF Aβ(42) level. The CSF tau and P-tau levels, but not the CSF Aβ(42) level, correlated with HV, suggesting that CSF tau markers reflect the neuronal loss associated with the physiopathological process of AD.

  7. Correlation of Objective Audiometric and Caloric Function in Ménière's Disease.

    PubMed

    McMullen, Kyle P; Lin, Chen; Harris, Michael S; Adunka, Oliver F

    2017-02-01

    Objective Ménière's disease affects the vestibular and audiologic systems; however, little is known about the relationship between audiometric and caloric function with increasing duration of disease. We employed a novel methodology to understand the longitudinal correlation between audiometric and caloric function in Ménière's patients. Study Design Case series with chart review. Setting Neuro-otologic tertiary care practice. Subjects and Methods Charts of 19 patients with unilateral Ménière's disease, as classified by the 1995 American Academy of Otolaryngology-Head and Neck Foundation criteria, were examined. We included patients with ≥2 videonystagmograms and audiograms. We excluded those with bilateral Ménière's, prior audiovestibular destruction, or symptoms suggesting concomitant vestibular pathology. Spearman's rank correlation of audiometric status (pure tone average [PTA], low PTA, and word recognition score [WRS]) and vestibular function (bithermal calorics) was performed. The study was Institutional Review Board approved (protocol 2015H0266). Results A total of 112 audiograms and 42 videonystagmographies were performed. There was a decline in affected ear hearing PTA and WRS with duration of disease ( r = 0.602, P < .001, and r = -0.573, P < .001, respectively). Similarly, there was a decline in vestibular function with increasing duration of disease ( r = 0.709, P < .001). There were moderate correlations between vestibular weakness and PTA, low PTA, and WRS ( r = 0.464, P = .002; r = 0.498, P = .001; and r = -0.518, P = .001, respectively). Conclusions There is a correlation between decline in objective hearing and horizontal semicircular canal function with time. As expected, this correlation is not 1:1, indicating differential involvement of both systems. Understanding this relationship may assist in counseling patients with regard to prognosis, natural history, and therapeutic interventions.

  8. Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases

    PubMed Central

    Guerreiro, Rita; Escott-Price, Valentina; Darwent, Lee; Parkkinen, Laura; Ansorge, Olaf; Hernandez, Dena G.; Nalls, Michael A.; Clark, Lorraine; Honig, Lawrence; Marder, Karen; van der Flier, Wiesje; Holstege, Henne; Louwersheimer, Eva; Lemstra, Afina; Scheltens, Philip; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Ortega-Cubero, Sara; Pastor, Pau; Ferman, Tanis J.; Graff-Radford, Neill R.; Ross, Owen A.; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Maetzler, Walter; Berg, Daniela; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Compta, Yaroslau; Revesz, Tamas; Lees, Andrew; Cairns, Nigel J.; Halliday, Glenda M.; Mann, David; Pickering-Brown, Stuart; Powell, John; Lunnon, Katie; Lupton, Michelle K.; Dickson, Dennis; Hardy, John; Singleton, Andrew; Bras, Jose

    2016-01-01

    The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD. PMID:26643944

  9. Genome-wide analysis of genetic correlation in dementia with Lewy bodies, Parkinson's and Alzheimer's diseases.

    PubMed

    Guerreiro, Rita; Escott-Price, Valentina; Darwent, Lee; Parkkinen, Laura; Ansorge, Olaf; Hernandez, Dena G; Nalls, Michael A; Clark, Lorraine; Honig, Lawrence; Marder, Karen; van der Flier, Wiesje; Holstege, Henne; Louwersheimer, Eva; Lemstra, Afina; Scheltens, Philip; Rogaeva, Ekaterina; St George-Hyslop, Peter; Londos, Elisabet; Zetterberg, Henrik; Ortega-Cubero, Sara; Pastor, Pau; Ferman, Tanis J; Graff-Radford, Neill R; Ross, Owen A; Barber, Imelda; Braae, Anne; Brown, Kristelle; Morgan, Kevin; Maetzler, Walter; Berg, Daniela; Troakes, Claire; Al-Sarraj, Safa; Lashley, Tammaryn; Compta, Yaroslau; Revesz, Tamas; Lees, Andrew; Cairns, Nigel J; Halliday, Glenda M; Mann, David; Pickering-Brown, Stuart; Powell, John; Lunnon, Katie; Lupton, Michelle K; Dickson, Dennis; Hardy, John; Singleton, Andrew; Bras, Jose

    2016-02-01

    The similarities between dementia with Lewy bodies (DLB) and both Parkinson's disease (PD) and Alzheimer's disease (AD) are many and range from clinical presentation, to neuropathological characteristics, to more recently identified, genetic determinants of risk. Because of these overlapping features, diagnosing DLB is challenging and has clinical implications since some therapeutic agents that are applicable in other diseases have adverse effects in DLB. Having shown that DLB shares some genetic risk with PD and AD, we have now quantified the amount of sharing through the application of genetic correlation estimates, and show that, from a purely genetic perspective, and excluding the strong association at the APOE locus, DLB is equally correlated to AD and PD.

  10. Structural Imaging Changes and Behavioral Correlates in Patients with Crohn’s Disease in Remission

    PubMed Central

    Nair, Veena A.; Beniwal-Patel, Poonam; Mbah, Ifeanyi; Young, Brittany M.; Prabhakaran, Vivek; Saha, Sumona

    2016-01-01

    Background: Crohn’s disease (CD) is a subtype of inflammatory bowel disease caused by immune-mediated inflammation in the gastrointestinal tract. The extent of morphologic brain alterations and their associated cognitive and affective impairments remain poorly characterized. Aims: We used magnetic resonance imaging to identify structural brain differences between patients with Crohn’s disease in remission compared to age-matched healthy controls and evaluated for structural-behavioral correlates. Methods: Nineteen patients and 20 healthy, age-matched controls were recruited in the study. Group differences in brain morphometric measures and correlations between brain measures and performance on a cognitive task, the verbal fluency (VF) task, were examined. Correlations between brain measures and cognitive measures as well as self-reported measures of depression, personality, and affective scales were examined. Results: Patients showed significant cortical thickening in the left superior frontal region compared to controls. Significant group differences were observed in sub-cortical volume measures in both hemispheres. Investigation of brain-behavior correlations revealed significant group differences in the correlation between cortical surface area and VF performance, although behavioral performance was equivalent between the two groups. The left middle temporal surface area was a significant predictor of VF performance with controls showing a significant positive correlation between these measures, and patients showing the opposite effect. Conclusion: Our results indicate key differences in structural brain measures in patients with CD compared to controls. Additionally, correlation between brain measures and behavioral responses suggest there may be a neural basis to the alterations in patients’ cognitive and affective responses. PMID:27695405

  11. Polygenic risk of Parkinson disease is correlated with disease age at onset

    PubMed Central

    Escott‐Price, Valentina; Nalls, Mike A.; Morris, Huw R.; Lubbe, Steven; Brice, Alexis; Gasser, Thomas; Heutink, Peter; Wood, Nicholas W.; Hardy, John; Singleton, Andrew B.

    2015-01-01

    Objective We have investigated the polygenic architecture of Parkinson disease (PD) and have also explored the potential relationship between an individual's polygenic risk score and their disease age at onset. Methods This study used genotypic data from 4,294 cases and 10,340 controls obtained from the meta‐analysis of PD genome‐wide association studies. Polygenic score analysis was performed as previously described by the International Schizophrenia Consortium, testing whether the polygenic score alleles identified in 1 association study were significantly enriched in the cases relative to the controls of 3 independent studies. Linear regression was used to investigate the relationship between an individual's polygenic score for PD risk alleles and disease age at onset. Results Our polygenic score analysis has identified significant evidence for a polygenic component enriched in the cases of each of 3 independent PD genome‐wide association cohorts (minimum p = 3.76 × 10−6). Further analysis identified compelling evidence that the average polygenic score in patients with an early disease age at onset was significantly higher than in those with a late age at onset (p = 0.00014). Interpretation This provides strong support for a large polygenic contribution to the overall heritable risk of PD and also suggests that early onset forms of the illness are not exclusively caused by highly penetrant Mendelian mutations, but can also be contributed to by an accumulation of common polygenic alleles with relatively low effect sizes. Ann Neurol 2015;77:582–591 PMID:25773351

  12. Seasonal Distribution and Climatic Correlates of Dengue Disease in Dhaka, Bangladesh.

    PubMed

    Morales, Ivonne; Salje, Henrik; Saha, Samir; Gurley, Emily S

    2016-06-01

    Dengue has been regularly reported in Dhaka, Bangladesh, since a large outbreak in 2000. However, to date, we have limited information on the seasonal distribution of dengue disease and how case distribution correlates with climate. Here, we analyzed dengue cases detected at a private diagnostic facility in Dhaka during 2010-2014. We calculated Pearson cross-correlation coefficients to examine the relationship between the timing of cases and both rainfall and temperature. There were 2,334 cases diagnosed during the study period with 76% over the age of 15 years. Cases were reported in every month of the study; however, 90% of cases occurred between June and November. Increases in rainfall were correlated with increases in cases 2 months later (correlation of 0.7). The large proportion of adult cases is consistent with substantial population susceptibility and suggests Dhaka remains at risk for outbreaks. Although cases occurred year-round, public health preparedness should be focused during peak months.

  13. Dengue in Vietnamese infants--results of infection-enhancement assays correlate with age-related disease epidemiology, and cellular immune responses correlate with disease severity.

    PubMed

    Chau, Tran Nguyen Bich; Quyen, Nguyen Than Ha; Thuy, Tran Thi; Tuan, Nguyen Minh; Hoang, Dang Minh; Dung, Nguyen Thi Phuong; Lien, Le Bich; Quy, Nguyen Thien; Hieu, Nguyen Trong; Hieu, Lu Thi Minh; Hien, Tran Tinh; Hung, Nguyen Thanh; Farrar, Jeremy; Simmons, Cameron P

    2008-08-15

    The pathogenesis of severe dengue is not well understood. Maternally derived subneutralizing levels of dengue virus-reactive IgG are postulated to be a critical risk factor for severe dengue during infancy. In this study, we found that, in healthy Vietnamese infants, there was a strong temporal association between the Fc-dependent, dengue virus infection-enhancing activity of neat plasma and the age-related epidemiology of severe dengue. We then postulated that disease severity in infants with primary infections would be associated with a robust immune response, possibly as a consequence of higher viral burdens in vivo. Accordingly, in infants hospitalized with acute dengue, the activation phenotype of peripheral-blood NK cells and CD8+ and CD4+ T cells correlated with overall disease severity, but HLA-A*1101-restricted NS3(133-142)-specific CD8+ T cells were not measurable until early convalescence. Plasma levels of cytokines/chemokines were generally higher in infants with dengue shock syndrome. Collectively, these data support a model of dengue pathogenesis in infants whereby antibody-dependent enhancement of infection explains the age-related case epidemiology and could account for antigen-driven immune activation and its association with disease severity. These results also highlight potential risks in the use of live attenuated dengue vaccines in infants in countries where dengue is endemic.

  14. Functional network connectivity analysis based on partial correlation in Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Zhang, Nan; Guan, Xiaoting; Zhang, Yumei; Li, Jingjing; Chen, Hongyan; Chen, Kewei; Fleisher, Adam; Yao, Li; Wu, Xia

    2009-02-01

    Functional network connectivity (FNC) measures the temporal dependency among the time courses of functional networks. However, the marginal correlation between two networks used in the classic FNC analysis approach doesn't separate the FNC from the direct/indirect effects of other networks. In this study, we proposed an alternative approach based on partial correlation to evaluate the FNC, since partial correlation based FNC can reveal the direct interaction between a pair of networks, removing dependencies or influences from others. Previous studies have demonstrated less task-specific activation and less rest-state activity in Alzheimer's disease (AD). We applied present approach to contrast FNC differences of resting state network (RSN) between AD and normal controls (NC). The fMRI data under resting condition were collected from 15 AD and 16 NC. FNC was calculated for each pair of six RSNs identified using Group ICA, thus resulting in 15 (2 out of 6) pairs for each subject. Partial correlation based FNC analysis indicated 6 pairs significant differences between groups, while marginal correlation only revealed 2 pairs (involved in the partial correlation results). Additionally, patients showed lower correlation than controls among most of the FNC differences. Our results provide new evidences for the disconnection hypothesis in AD.

  15. Disease activity in Graves' ophthalmopathy: diagnosis with orbital MR imaging and correlation with clinical score.

    PubMed

    Tortora, Fabio; Cirillo, Mario; Ferrara, Marco; Belfiore, Maria Paola; Carella, Carlo; Caranci, Ferdinando; Cirillo, Sossio

    2013-10-01

    In Graves' ophthalmopathy (GO) it is important to distinguish acute inflammation at an early stage, responsive to immunosuppressive treatment, from inactive fibrotic end stage disease, unresponsive to the same treatment. The purpose of this study was to identify the most relevant signal intensities on orbital MR imaging with contrast administration both to classify patients according to their clinical activity score (defined by a cut-off value of 3) and to make a prediction of patient's CAS. Such threshold was considered as widely used in literature. Sixteen consecutive patients with a diagnosis of GO in different phases of thyroid disease based on clinical and orbital MR imaging signs, and six normal volunteers were examined. Orbital MR imaging was performed on a 1.5 Tesla MR Unit. MR scans were assessed by an experienced neuroradiologist, blinded to the clinical examinations. We found a statistical correlation between CAS and both STIR and contrast enhanced T1-weighted sequences. There was also a statistically significant correlation between STIR and contrast-enhanced T1 images disclosing the possibility of avoiding the injection of contrast medium. Our study proved that signal intensity values on STIR sequence increase in the inflammatory oedematous phase of disease. We confirmed the correlation between signal intensities on this sequence and CAS, showing an increase in signal intensity proportional to the CAS value. So we validated MRI use to establish the activity phase of disease more sensitively than CAS alone.

  16. CTX Correlation to Disease Duration and Adiponectin in Egyptian Children with T1DM

    PubMed Central

    Hashim, Amel A.; Emara, Ibrahim A.; El-Hefnawy, Mohamed H.

    2016-01-01

    Summary Background In this study, we investigated the relationship of adiponectin with bone marker changes in Egyptian children and adolescents with T1DM and the effect of disease duration on these markers, as well as the possible correlations between adiponectin and bone markers in these patients. Methods Sixty Egyptian children and adolescent patients with T1DM were studied. Serum adiponectin and collagen breakdown products (cross-linked C-terminal telopeptide of collagen type l »CTX«) were measured and compared to the results of 20 age-matched healthy controls. Results After adjustment for age, BMI, Tanner stage and gender; (total) adiponectin was significantly higher in all T1DM patients. Serum level of CTX and 25(OH)D showed a marked decrease in diabetics with disease duration > 5 years. Serum level of (total) calcium and inorganic phosphorus (Pi) did not show significant difference from control. CTX was inversely correlated to FBG and T1DM duration. Pi was inversely, while 25(OH)D was directly correlated to FBG. Total calcium showed an inverse correlation with HbA1c. FBG, TC, TAG, LDL-C were independent predictors of CTX in T1DM. Conclusions Adiponectin showed no correlation with either CTX or bone homeostatic indices. FBG, TC, TAG, LDL-C were independent predictors of CTX in T1DM. We recommend further investigation of adiponectin isoforms in a population-based study, to establish a good age- and sex-related reference.

  17. Correlation of Sleep Disturbance and Cognitive Impairment in Patients with Parkinson’s Disease

    PubMed Central

    Kim, Eun Ja; Baek, Joon Hyun; Shin, Dong Jin; Park, Hyeon-Mi; Lee, Yeong-Bae; Park, Kee-Hyung; Shin, Dong Hoon; Noh, Young; Sung, Young Hee

    2014-01-01

    Objective Cognitive impairment is a common nonmotor symptom of Parkinson’s disease (PD) and is associated with high mortality, caregiver distress, and nursing home placement. The risk factors for cognitive decline in PD patients include advanced age, longer disease duration, rapid eye movement sleep behavior disorder, hallucinations, excessive daytime sleepiness, and nontremor symptoms including bradykinesia, rigidity, postural instability, and gait disturbance. We conducted a cross-sectional study to determine which types of sleep disturbances are related to cognitive function in PD patients. Methods A total of 71 PD patients (29 males, mean age 66.46 ± 8.87 years) were recruited. All patients underwent the Mini- Mental State Examination (MMSE) and the Korean Version of the Montreal Cognitive Assessments (MoCA-K) to assess global cognitive function. Sleep disorders were evaluated with the Stanford Sleepiness Scale, Epworth Sleepiness Scale, Insomnia Severity Index (ISI), Pittsburg Sleep Quality Index, and Parkinson’s Disease Sleep Scale in Korea (PDSS). Results The ISI was correlated with the MMSE, and total PDSS scores were correlated with the MMSE and the MoCA-K. In each item of the PDSS, nocturnal restlessness, vivid dreams, hallucinations, and nocturnal motor symptoms were positively correlated with the MMSE, and nocturnal restlessness and vivid dreams were significantly related to the MoCA-K. Vivid dreams and nocturnal restlessness are considered the most powerful correlation factors with global cognitive function, because they commonly had significant correlation to cognition assessed with both the MMSE and the MoCA-K. Conclusions We found a correlation between global cognitive function and sleep disturbances, including vivid dreams and nocturnal restlessness, in PD patients. PMID:24926405

  18. Correlation of different bone markers with bone density in patients with rheumatic diseases on glucocorticoid therapy.

    PubMed

    Loddenkemper, Konstanze; Bohl, Nicole; Perka, Carsten; Burmester, Gerd-Rüdiger; Buttgereit, Frank

    2006-02-01

    Osteoporosis is a common concomitant disease in patients with rheumatic diseases on glucocorticoid (GC) therapy. Bone status is usually evaluated by determination of bone density in combination with clinical examinations and laboratory tests. However, the strength of individual biochemical bone makers in GC-induced osteoporosis has yet to be fully clarified. For this reason, different bone markers were investigated in correlation with bone density in patients with rheumatic diseases. Approximately 238 patients (212 women, 26 men) with a rheumatic disease and under GC therapy were examined consecutively for the first time with regard to bone density (BMD) and bone markers [osteocalcin, bone-specific alkaline phosphatase (precipitation method/tandem-MP ostase), crosslinks [pyridinoline (PYD), deoxypyridinoline (DPX), N-terminal telopeptide (NTX)

  19. CSF findings in adrenoleukodystrophy: correlation between measures of cytokines, IgG production, and disease severity.

    PubMed

    Phillips, J P; Lockman, L A; Shapiro, E G; Blazar, B R; Loes, D J; Moser, H W; Krivit, W

    1994-06-01

    The childhood-onset cerebral form of adrenoleukodystrophy has a devastating neurologic prognosis. Unfortunately, there is no early method of distinguishing it from the more benign forms of adrenoleukodystrophy, such as adrenomyeloneuropathy. To evaluate the manner in which this disease entity may be reflected in the cerebrospinal fluid, we studied a consecutive series of 19 patients, all with biochemically proved adrenoleukodystrophy. total protein, immunoglobulin production, cytokine levels, and cerebrospinal fluid pressure were measured. In this single sample of cerebrospinal fluid, a significant correlation existed between clinical stage of the illness and cerebrospinal fluid myelin basic protein. No correlation existed with total protein, cytokines, or measures of immunoglobulin production.

  20. Inflammatory Leukocyte Phenotypes Correlate with Disease Progression in Idiopathic Pulmonary Fibrosis

    PubMed Central

    Moore, Bethany B.; Fry, Chris; Zhou, Yueren; Murray, Susan; Han, MeiLan K.; Martinez, Fernando J.; Flaherty, Kevin R.

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by progressive deposition of extracellular matrix, worsening dyspnea, and eventual mortality. Pathogenesis of IPF is poorly understood and the role inflammation and activated leukocytes play in the disease process is controversial. Previous studies demonstrated that activated leukocyte subsets characterize IPF patients. We sought to validate this observation in a well-defined cohort of 35 IPF patients and to correlate the observed leukocyte phenotypes with robust parameters of disease progression. We demonstrate that in univariate and multivariate analyses, increases in the CD14hi, CD16hi subset of monocytes measured at baseline correlated with disease progression, with a threshold value >0.5% of the total peripheral blood mononuclear cells being a significant predictor for worse outcome. In addition, several T cell subsets, including CD25 expressing CD4 cells, and CXCR3 expressing CD4 and CD8 subsets correlated with disease progression when found in increased percentages in the peripheral blood of IPF patients when sampled at baseline. Somewhat surprising in comparison to previous literature, the CD4 T cells did not appear to have lost expression of the co-stimulatory molecule, CD28, but the CD8 T cells did. Taken together, these results are consistent with the presence of an inflammatory process in IPF patients who eventually progress. However, when longitudinal measurements of these same markers were examined, there was significant heterogeneity of expression and these biomarkers did not necessarily remain elevated in IPF patients with progressive disease. We interpret this heterogeneity to suggest that IPF patients experience episodic inflammatory events that once triggered, may lead to disease progression. This longitudinal heterogeneity in biomarker analyses may explain why such markers are not consistently measured in all IPF cohorts. PMID:25580363

  1. The Correlation of CD206, CD209, and Disease Severity in Behçet's Disease with Arthritis

    PubMed Central

    Suh, Chang-Hee; Kim, Hyoun-Ah

    2017-01-01

    The purpose of this study was to clarify the role of pattern recognition receptors in Behçet's disease (BD). The frequencies of several pattern recognition receptors (CD11b, CD11c, CD32, CD206, CD209, and dectin-1) were analyzed in patients with BD by flow cytometry, and cytokine levels, interleukin- (IL-) 18, IL-23, and IL-17A, were compared in plasma. The analysis was performed in active (n = 13) and inactive (n = 13) stages of BD patients. Rheumatoid arthritis patients (n = 19), as a disease control, and healthy control (HC) (n = 19) were enrolled. The frequencies of CD11b+ and CD32+ cells were significantly increased in active BD patients compared to HC. Disease severity score was correlated to CD11c+, CD206+, and CD209+ in whole leukocytes and CD11b+, CD11c+, CD206+, CD209+, and Dectin-1+ in granulocytes. The plasma levels of IL-17A were significantly different between HC and active BD. IL-18 showed significant difference between active and inactive BD patients. From this study, we concluded the expressions of several pattern recognition receptors were correlated to the joint symptoms of BD. PMID:28377641

  2. Cardiac Effect of Interstitial Lung Disease Correlated with Spirometry and Six Minute Walk Test

    PubMed Central

    Agrawal, Mitali Bharat

    2017-01-01

    Introduction The cardiac effect of different pulmonary functions, six minute walk distance, arterial blood gases and saturation in Interstitial Lung Disease (ILD) is not much known. So this study, a tertiary care hospital experience that entails to know the various factors in Pulmonary Hypertension (PH) mentioned above causing PH and their correlation with PH. Aim To study the correlation of PH in patients with ILD with spirometry and six minute walk test (6MWT). Materials and Methods All consecutive patients with confirmed diagnosis of ILD taken over a period of 1½year in tertiary care hospital. 6MWT and spirometry were performed as per the American Thoracic Guidelines. Percent predicted 6 minute walk distance was calculated using Enright et al., and Indian reference equation. PH was diagnosed using 2-D echo. The spirometry variables and 6MWT were then correlated with the mean pulmonary artery pressure. Results There were 75 patients. About 66.66 % had PH on 2-D echo. The mean% predicted six minute walk distance as per the Indian reference equation, pre- and post- exercise PaO2 as well as desaturation had a significant correlation with PH. Spirometry variables Forced Expiratory Volume in First Second (FEV1) and Forced Vital Capacity (FVC) did not correlate with PH. Conclusion Thus, the 6MWT correlated significantly with PH while spirometry did not. PMID:28384908

  3. Alveolar hydatid disease of the liver: computed tomography and transabdominal ultrasound with histopathological correlation.

    PubMed

    Choji, K; Fujita, N; Chen, M; Spiers, A S; Morita, Y; Shinohara, M; Nojima, T; Irie, G

    1992-08-01

    The appearances of alveolar hydatid disease of the liver (AHDL) on computed tomography (CT) and ultrasound (US) were retrospectively compared with histopathological appearances in 67 patients with 100 separate lesions. The radiological features were correlated directly with the pathological specimens obtained from each patient. We conclude that the CT appearances are more specific, but that US has a role to play in mass screening in endemic areas, and intraoperatively.

  4. Pathogenesis of aphthoid ulcers in Crohn's disease: correlative findings by magnifying colonoscopy, electron microscopy, and immunohistochemistry.

    PubMed Central

    Fujimura, Y; Kamoi, R; Iida, M

    1996-01-01

    BACKGROUND--The mechanism of ulceration in Crohn's disease remains unknown. AIMS--To clarify the role of the follicle associated epithelium (FAE) of colonic lymphoid nodules in the formation of ulcers in Crohn's disease. METHODS--After identification of colonic lymphoid nodules and aphthoid lesions by magnifying colonoscopy, 76 biopsy specimens were obtained from 10 patients with Crohn's disease and three patients with colonic lymphoid hyperplasia. This study correlated magnifying colonoscopic, electron microscopic, and immunohistochemical findings of biopsy specimens. RESULTS--In Crohn's disease, scanning electron microscopy of lymphoid nodules surrounded by a red halo without visible erosions by magnifying colonoscopy, showed surface erosions 150-200 microns in size. These lymphoid nodules with red halos had small erosions either light microscopically or electron microscopically in 18 of 21 specimens (86%). Correlation of scanning and transmission electron microscopy showed residues of FAE including M cells at the edges of the erosions. In immunohistochemical studies, HLA-DR antigen was limited in M cells of FAE in the patients with lymphoid hyperplasia without inflammatory bowel disease. In Crohn's disease patients in remission, however, HLA-DR antigen was strongly expressed over the entire FAE of lymphoid nodules with a red halo endoscopically, while the expression was weak and irregular in the mucosa surrounding the lymphoid nodules. HLA-DR was strongly expressed in the entire inflamed colonic mucosa in the active stage. CONCLUSION--The red halo appearance surrounding lymphoid follicles seems to precede visible aphthoid ulcers and suggests that ulcerations in Crohn's disease originate from FAE, possibly related to its physiological role as a portal of entry for potentially pathogenic agents. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8707119

  5. Self-reported dysphagia and its correlates within a prevalent population of people with Parkinson's disease.

    PubMed

    Walker, Richard W; Dunn, Janet R; Gray, William K

    2011-03-01

    Many people with Parkinson's disease (PD) experience dysphagia; however, the prevalence of dysphagia in people with PD is unknown. We studied a prevalent population of PD cases. All of those who consented to participate were assessed for anxiety, depression, cognitive function, and quality of life using standard rating scales. Anyone who answered "yes" to either one of the two questions: Do you have difficulty swallowing food/liquid or tablets? and Do you cough after eating/drinking? was considered to have dysphagia. Question 7 of the Unified Parkinson's Disease Rating Scale (UPDRS) was also used to identify dysphagia. Of 106 prevalent PD cases, 75 (38 males) patients consented to examination and assessment. The prevalence of dysphagia was 32.0% (n=24; 11 males). Using the response to UPDRS Question 7 as an indicator of the impact of swallowing problems on the patient, there were significant correlations with cognitive function, anxiety, depression, quality of life, and UPDRS-reported gait disturbance, postural instability and problems with falling. There was no correlation with disease duration, age, or gender. Almost one third of the participants reported dysphagia. There was a strong correlation between dysphagia and gross motor skills; patients reporting such problems should be screened for swallowing problems.

  6. Topoisomerase II{alpha} expression correlates with diminished disease-free survival in invasive breast cancer

    SciTech Connect

    O'Connor, John K. . E-mail: joconno@yahoo.com; Hazard, Lisa J.; Lee, R. Jeffrey; Fischbach, Jennifer; Gaffney, David K.

    2006-08-01

    Purpose: Topoisomerase II{alpha} (Topo II{alpha}) plays a role in DNA replication and is the molecular target for anthracyline-based chemotherapy. The purpose of this study was to evaluate the relationship between Topo II{alpha} expression and survival in patients with invasive breast cancer. Methods and Materials: Formalin-fixed, paraffin-embedded tumor specimens from 24 women with invasive breast cancer were stained for Topo II{alpha} expression. All women underwent mastectomy. Radiotherapy was given at University of Utah Department of Radiation Oncology. Of the patients, 23 (96%) received chemotherapy. The level of Topo II{alpha} expression within tumor cells was compared with clinical factors and overall survival. Results: The median percentage of tumor cells expressing Topo II{alpha} was 70%. Increased Topo II{alpha} tumor expression significantly correlated with diminished disease-free survival. Five-year disease-free survival was 100% for patients with <70% of breast cancer cells expressing Topo II{alpha} compared with 42% for patients with {>=}70% Topo II{alpha} expression (p 0.008). The level of Topo II{alpha} expression within tumor cells correlated with T stage (p = 0.008) but not with other pathologic factors. Conclusions: Increased Topo II{alpha} expression significantly correlated with diminished disease-free survival in patients with invasive breast cancer. These findings may indicate a role for Topo II{alpha} expression as a prognostic factor in breast cancer.

  7. Herpes zoster correlates with increased risk of Parkinson's disease in older people

    PubMed Central

    Lai, Shih-Wei; Lin, Chih-Hsueh; Lin, Hsien-Feng; Lin, Cheng-Li; Lin, Cheng-Chieh; Liao, Kuan-Fu

    2017-01-01

    Abstract Little is known on the relationship between herpes zoster and Parkinson's disease in older people. This study aimed to explore whether herpes zoster could be associated with Parkinson's disease in older people in Taiwan. We conducted a retrospective cohort study using the claim data of the Taiwan National Health Insurance Program. There were 10,296 subjects aged 65 years and older with newly diagnosed herpes zoster as the herpes zoster group and 39,405 randomly selected subjects aged 65 years and older without a diagnosis of herpes zoster as the nonherpes zoster group from 1998 to 2010. Both groups were followed up until subjects received a diagnosis of Parkinson's disease. This follow-up design would explore whether subjects with herpes zoster were at an increased risk of Parkinson's disease. Relative risks were estimated by adjusted hazard ratio (HR) and 95% confidence interval (CI) using the multivariable Cox proportional hazards regression model. The incidence of Parkinson's disease was higher in the herpes zoster group than that in the nonherpes zoster group (4.86 vs 4.00 per 1000 person-years, 95% CI 1.14, 1.29). After adjustment for confounding factors, the multivariable Cox proportional hazards regression model revealed that the adjusted HR of Parkinson's disease was 1.17 for the herpes zoster group (95% CI 1.10, 1.25), compared with the nonherpes zoster group. Older people with herpes zoster confer a slightly increased hazard of developing Parkinson's disease when compared to those without herpes zoster. We think that herpes zoster correlates with increased risk of Parkinson's disease in older people. When older people with herpes zoster seek help, clinicians should pay more attention to the development of the cardinal symptoms of Parkinson's disease. PMID:28207515

  8. Paget disease of the vulva: a histologic study of 56 cases correlating pathologic features and disease course.

    PubMed

    Shaco-Levy, Ruthy; Bean, Sarah M; Vollmer, Robin T; Papalas, John A; Bentley, Rex C; Selim, Maria Angelica; Robboy, Stanley J

    2010-01-01

    The Duke experience with 56 vulvar Paget disease patients was analyzed emphasizing pathologic features and controversial issues. Nearly all patients were Caucasian, and their mean age was 69 years. The average length of follow-up was 5.6 years. For each case, the following histologic features were evaluated and their association with disease course was examined: pseudo-invasion, adnexal involvement, signet-ring cells, cytologic atypia, glands formation, epidermal acantholysis, parakeratosis, hyperkeratosis, and chronic inflammation. The recurrence rate after surgical management was 32%, with epidermal acantholysis being the only statistically significant risk factor. Stromal invasion occurred in 10 patients (18%), and was not a statistically significant adverse prognostic indicator, although the single patient who died of the disease had the deepest stromal invasion. Recurrence was more common after resections with positive surgical margins, but this correlation was not statistically significant. Intraoperative frozen section analysis of the margins did not reduce recurrence rate, nor was it useful in attaining permanent free margins. The Paget cells were consistently reactive with cytokeratin-7 and carcinoembryonic antigen and unreactive with S-100 protein, HMB-45, and Mart-1. In addition, the tumor cells were usually positive for mucin stains. This profile helps distinguish vulvar Paget disease from its mimics, Pagetoid squamous cell carcinoma and malignant melanoma.

  9. Stressful life events and psychosocial correlates of pediatric inflammatory bowel disease activity

    PubMed Central

    Giannakopoulos, George; Chouliaras, George; Margoni, Daphne; Korlou, Sophia; Hantzara, Vassiliki; Panayotou, Ioanna; Roma, Eleftheria; Liakopoulou, Magda; Anagnostopoulos, Dimitris C

    2016-01-01

    AIM To investigate the association of psychiatric and psychosocial correlates with inflammatory bowel disease (IBD) activity in children and adolescents. METHODS A total of 85 pediatric IBD patients (in remission or active state of the disease) and their parents completed a series of questionnaires and semi-structured interviews measuring life events, depression, anxiety, family dysfunction, and parent mental health. Differences between the remission and the IBD active group and the association of any significant variable with the disease activity state were examined. RESULTS Parents of children being in active state of the disease reported more life events (P = 0.005) and stressful life events (P = 0.048) during the past year and more mental health symptoms (P < 0.001), while the children themselves reported higher levels of anxiety symptoms (P = 0.017) compared to the remission group. In the logistic regression multivariate analysis, the only predictor which had a significant positive effect on the probability of the patients being in active state was parent mental health symptoms (OR = 4.8; 95%CI: 1.2-25.8). CONCLUSION Life events, child anxiety and parent mental health symptoms may be important correlates of pediatric IBD activity and targets of thorough assessment and treatment. PMID:27679771

  10. Neural correlates of attention‐executive dysfunction in lewy body dementia and Alzheimer's disease

    PubMed Central

    Kobeleva, Xenia; Cherry, George; Killen, Alison; Gallagher, Peter; Burn, David J.; Thomas, Alan J.; O'Brien, John T.; Taylor, John‐Paul

    2015-01-01

    Abstract Attentional and executive dysfunction contribute to cognitive impairment in both Lewy body dementia and Alzheimer's disease. Using functional MRI, we examined the neural correlates of three components of attention (alerting, orienting, and executive/conflict function) in 23 patients with Alzheimer's disease, 32 patients with Lewy body dementia (19 with dementia with Lewy bodies and 13 with Parkinson's disease with dementia), and 23 healthy controls using a modified Attention Network Test. Although the functional MRI demonstrated a similar fronto‐parieto‐occipital network activation in all groups, Alzheimer's disease and Lewy body dementia patients had greater activation of this network for incongruent and more difficult trials, which were also accompanied by slower reaction times. There was no recruitment of additional brain regions or, conversely, regional deficits in brain activation. The default mode network, however, displayed diverging activity patterns in the dementia groups. The Alzheimer's disease group had limited task related deactivations of the default mode network, whereas patients with Lewy body dementia showed heightened deactivation to all trials, which might be an attempt to allocate neural resources to impaired attentional networks. We posit that, despite a common endpoint of attention‐executive disturbances in both dementias, the pathophysiological basis of these is very different between these diseases. Hum Brain Mapp 37:1254–1270, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26705763

  11. Parenchymal opacification in chronic infiltrative lung diseases: CT-pathologic correlation.

    PubMed

    Leung, A N; Miller, R R; Müller, N L

    1993-07-01

    To correlate areas of parenchymal opacification on thin-section computed tomographic (CT) scans with histologic findings in patients with chronic infiltrative lung disease, the CT and histologic findings were evaluated in 29 patients with 11 such diseases. Open-lung biopsy was performed after CT. The area of predominant involvement was classified as air space, interstitium, or a mixture of both. A pathologic score of disease activity was assigned, and the extent of fibrosis was assessed whenever fibrosis was present. Parenchymal opacification on CT scans corresponded to abnormalities that affected mainly the air spaces in three patients (10%), the interstitium in 13 patients (45%), or both to a similar degree in 13 patients (45%). In 25 of 29 patients (86%), parenchymal opacification was associated with potentially treatable or reversible disease. Abnormalities considered irreversible were seen in three patients with end-stage fibrosis and one patient with talcosis. Parenchymal opacification on thin-section CT scans is a nonspecific finding in diseases that affect the air spaces, interstitium, or both but usually indicates potentially treatable or reversible disease.

  12. Correlation of disease activity in proliferative glomerulonephritis with glomerular spleen tyrosine kinase expression.

    PubMed

    McAdoo, Stephen P; Bhangal, Gurjeet; Page, Theresa; Cook, H Terence; Pusey, Charles D; Tam, Frederick W K

    2015-07-01

    Spleen tyrosine kinase (SYK) is an important component of the intracellular signaling pathway for various immunoreceptors. Inhibition of SYK has shown promise in preclinical models of autoimmune and glomerular disease. However, the description of SYK expression in human renal tissue, which would be desirable ahead of clinical studies, is lacking. Here we conducted immunohistochemical analysis for total and phosphorylated SYK in biopsy specimens from >120 patients with a spectrum of renal pathologies, including thin basement membrane lesion, minimal change disease, membranous nephropathy, IgA nephropathy, lupus nephritis, ANCA-associated glomerulonephritis, antiglomerular basement membrane disease, and acute tubular necrosis. We found significant SYK expression in proliferative glomerulonephritis and that glomerular expression levels correlated with presenting serum creatinine and histological features of disease activity that predict outcome in IgA nephropathy, lupus nephritis, ANCA-associated glomerulonephritis, and antiglomerular basement membrane disease. SYK was phosphorylated within pathological lesions, such as areas of extracapillary and endocapillary proliferation, and appeared to localize to both infiltrating leucocytes and to resident renal cells within diseased glomeruli. Thus SYK is associated with the pathogenesis of proliferative glomerulonephritides, suggesting that these conditions may respond to SYK inhibitor treatment.

  13. Neural correlates of attention-executive dysfunction in lewy body dementia and Alzheimer's disease.

    PubMed

    Firbank, Michael; Kobeleva, Xenia; Cherry, George; Killen, Alison; Gallagher, Peter; Burn, David J; Thomas, Alan J; O'Brien, John T; Taylor, John-Paul

    2016-03-01

    Attentional and executive dysfunction contribute to cognitive impairment in both Lewy body dementia and Alzheimer's disease. Using functional MRI, we examined the neural correlates of three components of attention (alerting, orienting, and executive/conflict function) in 23 patients with Alzheimer's disease, 32 patients with Lewy body dementia (19 with dementia with Lewy bodies and 13 with Parkinson's disease with dementia), and 23 healthy controls using a modified Attention Network Test. Although the functional MRI demonstrated a similar fronto-parieto-occipital network activation in all groups, Alzheimer's disease and Lewy body dementia patients had greater activation of this network for incongruent and more difficult trials, which were also accompanied by slower reaction times. There was no recruitment of additional brain regions or, conversely, regional deficits in brain activation. The default mode network, however, displayed diverging activity patterns in the dementia groups. The Alzheimer's disease group had limited task related deactivations of the default mode network, whereas patients with Lewy body dementia showed heightened deactivation to all trials, which might be an attempt to allocate neural resources to impaired attentional networks. We posit that, despite a common endpoint of attention-executive disturbances in both dementias, the pathophysiological basis of these is very different between these diseases.

  14. Correlation between Serum RANTES Levels and the Severity of Parkinson's Disease

    PubMed Central

    Tang, Peng; Chong, Li; Li, Xiaoqing; Liu, Yue; Liu, Peng; Hou, Chen; Li, Rui

    2014-01-01

    Inflammatory mediators may reflect a role of systemic inflammation in the neurodegenerative process of Parkinson's disease (PD). Interleukin-6 (IL-6) and chemokine ligand 5 (CCL5), also known as RANTES (regulated on activation, normal T cell expressed and secreted), have been implicated in neurodegenerative diseases including PD. Serum levels of RANTES and IL-6 of 78 consecutive PD patients and age-matched 80 controls were measured. Patients with PD had higher RANTES and IL-6 levels compared with the controls. We found that serum RANTES levels strongly correlated with Hoehn-Yahr score and disease duration in PD patients. This study indicated that patients with PD have an on-going systemic inflammatory profile where the elevated peripheral production of RANTES may play a role in the neurodegenerative process. PMID:25587378

  15. Correlation between serum RANTES levels and the severity of Parkinson's disease.

    PubMed

    Tang, Peng; Chong, Li; Li, Xiaoqing; Liu, Yue; Liu, Peng; Hou, Chen; Li, Rui

    2014-01-01

    Inflammatory mediators may reflect a role of systemic inflammation in the neurodegenerative process of Parkinson's disease (PD). Interleukin-6 (IL-6) and chemokine ligand 5 (CCL5), also known as RANTES (regulated on activation, normal T cell expressed and secreted), have been implicated in neurodegenerative diseases including PD. Serum levels of RANTES and IL-6 of 78 consecutive PD patients and age-matched 80 controls were measured. Patients with PD had higher RANTES and IL-6 levels compared with the controls. We found that serum RANTES levels strongly correlated with Hoehn-Yahr score and disease duration in PD patients. This study indicated that patients with PD have an on-going systemic inflammatory profile where the elevated peripheral production of RANTES may play a role in the neurodegenerative process.

  16. Correlation of Visuospatial Ability and EEG Slowing in Patients with Parkinson's Disease

    PubMed Central

    Meyer, Antonia; Chaturvedi, Menorca; Hatz, Florian; Gschwandtner, Ute

    2017-01-01

    Background. Visuospatial dysfunction is among the first cognitive symptoms in Parkinson's disease (PD) and is often predictive for PD-dementia. Furthermore, cognitive status in PD-patients correlates with quantitative EEG. This cross-sectional study aimed to investigate the correlation between EEG slowing and visuospatial ability in nondemented PD-patients. Methods. Fifty-seven nondemented PD-patients (17 females/40 males) were evaluated with a comprehensive neuropsychological test battery and a high-resolution 256-channel EEG was recorded. A median split was performed for each cognitive test dividing the patients sample into either a normal or lower performance group. The electrodes were split into five areas: frontal, central, temporal, parietal, and occipital. A linear mixed effects model (LME) was used for correlational analyses and to control for confounding factors. Results. Subsequently, for the lower performance, LME analysis showed a significant positive correlation between ROCF score and parietal alpha/theta ratio (b = .59, p = .012) and occipital alpha/theta ratio (b = 0.50, p = .030). No correlations were found in the group of patients with normal visuospatial abilities. Conclusion. We conclude that a reduction of the parietal alpha/theta ratio is related to visuospatial impairments in PD-patients. These findings indicate that visuospatial impairment in PD-patients could be influenced by parietal dysfunction. PMID:28348918

  17. Anatomical correlates of sentence comprehension and verbal working memory in neurodegenerative disease.

    PubMed

    Amici, Serena; Brambati, Simona M; Wilkins, David P; Ogar, Jennifer; Dronkers, Nina L; Miller, Bruce L; Gorno-Tempini, Maria Luisa

    2007-06-06

    This study investigates whether sentence comprehension and nonsyntactic verbal working memory (vWM) are sustained by the same or by different neural systems. Scores in a sentence-picture matching task and in digits backward (DB) were correlated with magnetic resonance imaging voxelwise gray matter volumes using voxel-based morphometry in 58 patients with neurodegenerative diseases. Results showed that overall sentence comprehension scores, regardless of grammatical structure, correlated with gray matter volumes in the left temporoparietal region, whereas DB scores correlated with dorsolateral prefrontal and inferior parietal volumes. Comprehension of multiclausal relative sentences (type 3) significantly correlated with voxels in the dorsal portion of the left inferior and middle frontal gyri. When DB and multiclausal relative sentences were directly compared, they showed overlapping neural substrates in the dorsolateral left frontal region, supporting a single source of vWM for syntactic and nonsyntactic tasks. Within this large area of common involvement, a small portion of pars triangularis showed an independent effect of multiclausal sentences, whereas a region in the middle frontal gyrus showed greater correlation with DB. This study reconciles two opposing views, which hold that sentence comprehension and vWM rely on either the same or different anatomical resources.

  18. Muscle MRI Findings in Childhood/Adult Onset Pompe Disease Correlate with Muscle Function

    PubMed Central

    Figueroa-Bonaparte, Sebastián; Segovia, Sonia; Llauger, Jaume; Belmonte, Izaskun; Pedrosa, Irene; Alejaldre, Aída; Mayos, Mercè; Suárez-Cuartín, Guillermo; Gallardo, Eduard; Illa, Isabel; Díaz-Manera, Jordi

    2016-01-01

    Objectives Enzyme replacement therapy has shown to be effective for childhood/adult onset Pompe disease (AOPD). The discovery of biomarkers useful for monitoring disease progression is one of the priority research topics in Pompe disease. Muscle MRI could be one possible test but the correlation between muscle MRI and muscle strength and function has been only partially addressed so far. Methods We studied 34 AOPD patients using functional scales (Manual Research Council scale, hand held myometry, 6 minutes walking test, timed to up and go test, time to climb up and down 4 steps, time to walk 10 meters and Motor Function Measure 20 Scale), respiratory tests (Forced Vital Capacity seated and lying, Maximun Inspiratory Pressure and Maximum Expiratory Pressure), daily live activities scales (Activlim) and quality of life scales (Short Form-36 and Individualized Neuromuscular Quality of Life questionnaire). We performed a whole body muscle MRI using T1w and 3-point Dixon imaging centered on thighs and lower trunk region. Results T1w whole body muscle MRI showed a homogeneous pattern of muscle involvement that could also be found in pre-symptomatic individuals. We found a strong correlation between muscle strength, muscle functional scales and the degree of muscle fatty replacement in muscle MRI analyzed using T1w and 3-point Dixon imaging studies. Moreover, muscle MRI detected mild degree of fatty replacement in paraspinal muscles in pre-symptomatic patients. Conclusion Based on our findings, we consider that muscle MRI correlates with muscle function in patients with AOPD and could be useful for diagnosis and follow-up in pre-symptomatic and symptomatic patients under treatment. Take home message Muscle MRI correlates with muscle function in patients with AOPD and could be useful to follow-up patients in daily clinic. PMID:27711114

  19. Polysomnographic Findings and Clinical Correlates in Huntington Disease: A Cross-Sectional Cohort Study

    PubMed Central

    Piano, Carla; Losurdo, Anna; Della Marca, Giacomo; Solito, Marcella; Calandra-Buonaura, Giovanna; Provini, Federica; Bentivoglio, Anna Rita; Cortelli, Pietro

    2015-01-01

    Study Objectives: To evaluate the sleep pattern and the motor activity during sleep in a cohort of patients affected by Huntington disease (HD). Design: Cross-sectional cohort study. Setting: Sleep laboratory. Patients: Thirty HD patients, 16 women and 14 men (mean age 57.3 ± 12.2 y); 30 matched healthy controls (mean age 56.5 ± 11.8 y). Interventions: Subjective sleep evaluation: Epworth Sleepiness Scale (ESS); Berlin's Questionnaire, interview for restless legs syndrome (RLS), questionnaire for REM sleep behavior disorder (RBD). Clinical evaluation: disease duration, clinical severity (unified Huntington disease motor rating scale [UHDMRS]), genetic tests. Laboratory-based full-night attended video-polysomnography (V-PSG). Measurements and Results: The duration of the disease was 9.4 ± 4.4 y, UHMDRS score was 55.5 ± 23.4, CAG repeats were 44.3 ± 4.1. Body mass index was 21.9 ± 4.0 kg/m2. No patients or caregivers reported poor sleep quality. Two patients reported symptoms of RLS. Eight patients had an ESS score ≥ 9. Eight patients had high risk of obstructive sleep apnea. At the RBD questionnaire, two patients had a pathological score. HD patients, compared to controls, showed shorter sleep, reduced sleep efficiency index, and increased arousals and awakenings. Four patients presented with sleep disordered breathing (SDB). Periodic limb movements (PLMs) during wake and sleep were observed in all patients. No episode of RBD was observed in the V-PSG recordings, and no patients showed rapid eye movement (REM) sleep without atonia. The disease duration correlated with ESS score (P < 0.02). UHMDRS correlated positively with the ESS score (P < 0.005), and negatively with the percentage of REM sleep. Conclusions: Patients with Huntington disease showed a severe sleep disruption and a high prevalence of periodic limb movements, but no evidence of sleep disordered breathing or REM sleep behavior disorder. Citation: Piano C, Losurdo A, Della Marca G, Solito M

  20. Correlation of serum neutrophil gelatinase associated lipocalin with disease severity in hypertensive disorders of pregnancy

    PubMed Central

    Sachan, Rekha; Patel, ML; Gaurav, Amrita; Gangwar, Radheshyam; Sachan, Pushpalata

    2014-01-01

    Background: Vascular endothelial dysfunction is considered central to the pathogenesis of hypertensive disorders of pregnancy (HDP). Serum level of neutrophil gelatinase-associated lipocalin (NGAL) is closely related to endothelial injury. The aim of this study was to examine the correlation of serum NGAL with disease severity in HDP. Materials and Methods: This prospective case-control study was carried out for one year. After informed consent, ethical clearance, total 1,850 pregnant women were screened. Analysis was performed on 142 cases of HDP and 31 healthy controls. Quantitative measurement of serum NGAL levels was done by the enzyme linked immunosorbent assay (ELISA) technique, by using sandwich ELISA kit. Results: Mean serum NGAL value in patients with oliguria was significantly higher when compared with non-oliguric patients (P < 0.001). Serum NGAL had a positive correlation with systolic blood pressure (r ~ 0.5973), diastolic blood pressure (r ~ 0.6195), blood urea (r ~ 0.4392), serum creatinine (r ~ 0.6112), serum uric acid (r ~ 0.3878). Sensitivity and specificity of serum NGAL using a cut-off value of 545 pg/ml, for the diagnosis of HDP, was 97.89% and 93.55% respectively, using 95% confidence interval. Conclusion: Between the two groups, we found that serum NGAL had a positive correlation with disease severity and better sensitivity and specificity in the evaluation of HDP. PMID:25538909

  1. N30 Somatosensory Evoked Potential Is Negatively Correlated with Motor Function in Parkinson’s Disease

    PubMed Central

    Kang, Suk Yun; Ma, Hyeo-Il

    2016-01-01

    Objective The aim of this study was to investigate frontal N30 status in Parkinson’s disease (PD) and to examine the correlation between the amplitude of frontal N30 and the severity of motor deficits. Methods The frontal N30 was compared between 17 PD patients and 18 healthy volunteers. Correlations between the amplitude of frontal N30 and the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score of the more severely affected side was examined. Results The mean latency of the N30 was not significantly different between patients and healthy volunteers (p = 0.981), but the mean amplitude was lower in PD patients (p < 0.025). There was a significant negative correlation between the amplitude of N30 and the UPDRS motor score (r = -0.715, p = 0.013). Conclusions The frontal N30 status indicates the motor severity of PD. It can be a useful biomarker reflecting dopaminergic deficits and an objective measurement for monitoring the clinical severity of PD. PMID:26828214

  2. Hope and spirituality among patients with chronic kidney disease undergoing hemodialysis: a correlational study1

    PubMed Central

    Ottaviani, Ana Carolina; Souza, Érica Nestor; Drago, Natália de Camargo; de Mendiondo, Marisa Silvana Zazzetta; Pavarini, Sofia Cristina Iost; Orlandi, Fabiana de Souza

    2014-01-01

    Objective to analyze the relationship between the hope and spirituality of patients with chronic kidney disease undergoing hemodialysis. Method this is a cross-sectional, correlational study. The sample was composed of 127 patients of a Renal Replacement Unit. Data were collected through individual interviews guided by the following instruments: participant characterization, Herth Hope Index (HHI), and Pinto Pais-Ribeiro Spirituality Scale (PP-RSS). Results the average HHI score was 38.06 (±4.32) while the average PP-RSS score was 3.67 (±0.62) for "beliefs" and 3.21 (±0.53) for "hope/optimism". Spearman's coefficient indicated there was a moderate positive correlation between the HHI and PP-RSS dimensions of "beliefs" (r=0.430; p<0.001) and "hope/optimism" (r=0.376; p<0.001). Conclusion Since a relationship between the sense of hope and spirituality of patients with chronic kidney disease was found, these constructs should be taken into account at the time health professionals deliver care to help patients coping with the disease and treatment. PMID:26107832

  3. Mediastinal germ cell tumors: a radiologic-pathologic review.

    PubMed

    Drevelegas, A; Palladas, P; Scordalaki, A

    2001-01-01

    Germ cell tumors of the mediastinum are histologically identical to those found in the testes and ovaries. Early diagnosis and treatment improve the survival rate. Imaging studies of teratoma demonstrate a rounded, often lobulated heterogeneous mass containing soft tissue elements with fluid and fat attenuation. Calcification is present in 20-43% of cases. Seminomas are large masses of homogeneous soft tissue attenuation. Malignant nonseminomatous germ cell tumors are heterogeneous tumors with irregular borders due to invasion of adjacent structures. CT shows the location and extent of the tumors as well as intrinsic elements including soft tissue, fat, fluid, and calcification. CT is the modality of choice for the diagnostic evaluation of these tumors. MRI reveals masses of heterogeneous signal intensity, is more sensitive in depicting infiltration of the adjacent structures by fat plane obliteration, and is performed as an ancillary study.

  4. Primary Diffuse Leptomeningeal Gliomatosis: Radiological/Pathological Features

    PubMed Central

    Mohamed, Mohamed

    2016-01-01

    We present the case of a 43-year-old lady who presented with headaches, visual impairment, and seizures, progressing rapidly over the course of a few weeks. Extensive workup excluded an inflammatory or infectious cause. Imaging studies revealed diffuse thickening of the leptomeninges and serial CSF analysis showed raised opening pressures and increased protein levels. A diagnostic biopsy of the lower thoracic dura confirmed the diagnosis of primary diffuse leptomeningeal gliomatosis (PDGL). She was managed supportively for her symptoms and unfortunately she passed away a few weeks later. PMID:27891270

  5. Correlation between plasma angiopoietin-1, angiopoietin-2 and matrix metalloproteinase-2 in coronary heart disease

    PubMed Central

    Wu, Haoyu; Shou, Xiling; Liang, Lei; Yao, Xiaowei; Cheng, Gong

    2016-01-01

    Introduction Angiopoietin-2 (Ang-2) plays a critical role in inducing tumor cell infiltration, and this invasive phenotype is caused by up-regulation of matrix metalloproteinase (MMP)-2. The relationship between Ang-2 and MMP-2 in atherosclerosis has not been reported yet. The aim is to measure the plasma concentrations of Ang-1, Ang-2 and MMP-2 and assess the correlation between the concentrations of these factors in coronary heart disease (CHD) patients. Material and methods The testing was done in a cross-sectional study. We prospectively enrolled 42 individuals with acute myocardial infarction, 42 individuals with unstable angina pectoris, 42 individuals with stable angina pectoris and 45 healthy control subjects. Concentrations of Ang-1, Ang-2 and MMP-2 were measured using the enzyme-linked immunosorbent assay (ELISA) method. Spearman’s rank correlation was calculated to evaluate the relationships between MMP-2 and Ang-1, and MMP-2 and Ang-2 in patients with CHD. Results Patients with acute myocardial infarction and unstable angina pectoris had higher Ang-2 and MMP-2 levels compared with stable angina patients and healthy control subjects (p < 0.05), while concentrations of Ang-1 were not statistically different between the groups. Spearman’s rank correlation showed that Ang-2 levels positively correlated with MMP-2 in patients with CHD (r = 0.679, p < 0.001). Conclusions Plasma Ang-2 and MMP-2 levels but not Ang-1 levels were increased in patients with CHD. Ang-1 correlated weakly with MMP-2, whereas the Ang-2 and MMP-2 correlation was strong in patients with CHD. Ang-2 may play a role in atherosclerosis, and have an interaction with MMP-2. PMID:27904510

  6. Hippocampal phospho-tau/MAPT neuropathology in the fornix in Alzheimer disease: an immunohistochemical autopsy study.

    PubMed

    Plowey, Edward D; Ziskin, Jennifer L

    2016-10-28

    -MAPT progression from the hippocampal formation and underscore a need for additional clinical-radiologic-pathologic correlation studies.

  7. Correlating DWI MRI with pathological and other features of Jakob-Creutzfeldt disease

    PubMed Central

    Geschwind, Michael D.; Potter, Christopher A.; Sattavat, Mamta; Garcia, Paul A.; Rosen, Howard J.; Miller, Bruce L.; DeArmond, Stephen J.

    2009-01-01

    Diffusion-weighted (DWI) MRI is a highly sensitive and specific test for diagnosis of sporadic Jakob-Creutzfeldt disease (sCJD); however, the neuropathological origin of DWI signal abnormalities including other clinical features have not been well-defined. We describe a case of sCJD with brain MRI taken 15 days prior to death, which provided an opportunity to correlate clinical, EEG, MRI and neuropathological findings in order to better understand which sCJD-specific neuropathological changes underlie the DWI abnormalities. Clinical findings correlated well with both EEG and MRI changes. Neuropathological analysis showed that hyperintensities on DWI MRI correlated best with the vacuolation score (r=0.78, p=0.0005) and PrPSc load (r=0.77; p=0.0006), followed by reactive astrocytic gliosis (r=0.63, p=0.008). This case provides further evidence that DWI abnormalities correlate well with the clinical features and with PrPSc accumulation and vacuolation. PMID:19266702

  8. Correlation between Limb Muscle Endurance, Strength, and Functional Capacity in People with Chronic Obstructive Pulmonary Disease

    PubMed Central

    Törnberg, Anna; Wadell, Karin

    2016-01-01

    Purpose: To examine the correlation between limb muscle function (endurance and strength) and functional capacity in upper limbs (ULs) and lower limbs (LLs) of people with chronic obstructive pulmonary disease (COPD). Method: This article describes a secondary analysis of data from a randomized controlled trial. A stationary dynamometer was used to measure isokinetic muscle strength and endurance; the 6-minute walk test, the 6-minute pegboard and ring test, and the unsupported UL exercise test were used to measure functional capacity. Results: Participants were 44 adults with COPD. Muscle strength and endurance in ULs and LLs demonstrated a moderate to strong correlation with functional capacity. When controlling for muscle strength, muscle endurance was moderately correlated with functional capacity in ULs and LLs, but when controlling for muscle endurance, there was no positive and significant correlation between muscle strength and functional capacity for the ULs or LLs. Conclusions: Functional capacity seems to be more closely related to limb muscle endurance than to limb muscle strength in people with COPD. PMID:27504047

  9. The Geomagnetic Field and Correlations with Multiple Sclerosis: A Possible Etiology of Disease

    NASA Astrophysics Data System (ADS)

    Wade, Brett

    Multiple sclerosis (MS) is a complex autoimmune disease that results in a demyelinating process of the central nervous system. It is the most common, progressive, neurological disease affecting young adults, and there is no cure. A curious feature of MS is its distinct global prevalence with high rates of occurrence between 40 and 60 degrees latitude. While genetics may partially explain this phenomenon, studies have shown that the influence of genetics is modest. Many non-genetic variables, such as viruses, vitamin D, smoking, diet, hormones, etc., have been shown to be related to the expression of MS but none of these variables have been determined to be necessarily strong enough to exclude other factors. The geomagnetic field, which is a non-uniform, three dimensional entity which protects all living things from ionizing radiation, is suggested in this research to be related to global MS prevalence. This study hypothesized that either the total field, the vertical field, or the horizontal field strength of the geomagnetic field will be correlated with MS. Using secondary sources of prevalence studies (N=131) and geomagnetic data, the results supported all three hypotheses with the strongest correlation being an inverse relationship between the horizontal field and MS (r = -.607). The explanation for the inverse relationship being most strongly correlated with MS prevalence is explained by the fact that the horizontal aspect of the geomagnetic field has a protective effect from incoming cosmic radiation. Chronic exposure to high levels of background radiation can have deleterious health effects. This research suggests that living in areas of a weak horizontal field increases a person's exposure to ionizing radiation and therefore increases the risk for developing MS. While it was not the intention of this research, it became clear that an explanation which explained the results of this research and also attempted to unify the mechanisms of all non

  10. Correlates of Excessive Daytime Sleepiness in De Novo Parkinson's Disease: A Case Control Study

    PubMed Central

    Simuni, Tanya; Caspell-Garcia, Chelsea; Coffey, Christopher; Chahine, Lama M.; Lasch, Shirley; Oertel, Wolfgang H.; Mayer, Geert; Högl, Birgit; Postuma, Ron; Videnovic, Aleksandar; Amara, Amy Willis; Marek, Ken

    2016-01-01

    Objective This study was undertaken to determine the frequency and correlates of excessive daytime sleepiness in de novo, untreated Parkinson's disease (PD) patients compared with the matched healthy controls. Methods Data were obtained from the Parkinson's Progression Markers Initiative, an international study of de novo, untreated PD patients and healthy controls. At baseline, participants were assessed with a wide range of motor and nonmotor scales, including the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Excessive daytime sleepiness was assessed based on the Epworth Sleepiness scale (ESS), with a cutoff of 10. Results Four hundred twenty-three PD subjects and 196 healthy controls were recruited into the study. Mean ESS (min, max) score was 5.8 (0, 20) for the PD subjects and 5.6 (0, 19) for healthy controls (P = 0.54). Sixty-six (15.6%) PD subjects and 24 (12%) healthy controls had ESS of at least 10 (P = 0.28). No difference was seen in demographic characteristics, age of onset, disease duration, PD subtype, cognitive status, or utilization of sedatives between the PD sleepiness-positive versus the negative group. The sleepiness-positive group had higher MDS-UPDRS Part I and II but not III scores, and higher depression and autonomic dysfunction scores. Sleepiness was associated with a marginal reduction of A-beta (P = 0.05) but not alpha-synuclein spinal fluid levels in PD. Conclusions This largest case control study demonstrates no difference in prevalence of excessive sleepiness in subjects with de novo untreated PD compared with healthy controls. The only clinical correlates of sleepiness were mood and autonomic dysfunction. Ongoing longitudinal analyses will be essential to further examine clinical and biological correlates of sleepiness in PD and specifically the role of dopaminergic therapy. PMID:26095202

  11. Appearance of monoclonal plasma cell diseases in whole-body magnetic resonance imaging and correlation with parameters of disease activity.

    PubMed

    Kloth, Jost K; Hillengass, Jens; Listl, Karin; Kilk, Kerstin; Hielscher, Thomas; Landgren, Ola; Delorme, Stefan; Goldschmidt, Hartmut; Kauczor, Hans-Ulrich; Weber, Marc-André

    2014-11-15

    The aim of our study was to assess in which way different infiltration patterns of monoclonal plasma cell diseases in whole-body (wb) magnetic resonance imaging (MRI) are associated with clinical stages, plasma cell content in bone marrow samples and established serum markers of disease activity. Institutional review board approval was obtained. We performed wb-MRI in 547 consecutive, unselected and untreated patients with monoclonal gammopathy of undetermined significance (MGUS, n=138), smoldering myeloma (SMM, n=157) and multiple myeloma (MM, n=252) on two 1.5 T MRI-scanners with body array coils. The studies were evaluated in consensus by two experienced radiologists blinded to the diagnosis. We observed focal lesions in 23.9% (MGUS), 34.4% (SMM) and 81.3% (MM), respectively. A diffuse infiltration pattern was detected in 38.4%, 45.9% and 71%, respectively. The differences between all infiltration patterns were significant (p<0.0001). The presence of focal lesions and the presence of a diffuse bone marrow infiltration was associated with an increased plasma cell percentage in bone marrow samples (median 22% vs. 14%, 26% vs. 10%, both p<0.0001) and monoclonal protein concentration (median 18 g/dl vs. 13 g/dl, p=0.003, 20 g/dl vs. 11 g/dl, p<0.0001). Further categorization of the diffuse infiltration patterns in wb-MRI into "salt-and-pepper," moderate and severe identified significant associations with M-protein (median g/dl for S+P/moderate/severe 23/18/25, p=0.04), plasma cell percentage in the bone marrow (median 25%/24%/40%, p=0.02), and age (median years 67/60/57, p<0.0001). Bone marrow infiltration in wb-MRI is significantly different between the various stages of plasma cell disease and correlates well with established markers of disease activity.

  12. Homovanillic acid in CSF of mild stage Parkinson's disease patients correlates with motor impairment.

    PubMed

    Stefani, Alessandro; Pierantozzi, Mariangela; Olivola, Enrica; Galati, Salvatore; Cerroni, Rocco; D'Angelo, Vincenza; Hainsworth, Atticus H; Saviozzi, Valentina; Fedele, Ernesto; Liguori, Claudio

    2017-05-01

    In Parkinson's disease (PD), several efforts have been spent in order to find biochemical parameters able to identify the progression of the pathological processes at the basis of the disease. It is already known that advanced PD patients manifesting dyskinesia are featured by the high homovanillic acid (HVA)/dopamine (DA) ratio, suggesting the increased turnover of DA in these patients. Less clear is whether similar changes affect mild and moderate stages of the disease (between 1 and 2.5 of Hoehn & Yahr -H&Y- stage). Hence, here we tested whether cerebrospinal fluid (CSF) concentrations of DA and its major metabolites, either 3,4-dihydroxyphenylacetic acid (DOPAC) or HVA, correlate with motor performance in mild and moderate PD patients. CSF samples were collected after 2 days of anti-PD drugs washout, via lumbar puncture (LP) performed 130 min following administration of oral levodopa (LD) dose (200 mg). LP timing was determined in light of our previous tests clarifying that 2 h after oral LD administration CSF DA concentration reaches a plateau, which was un-respective of PD stage or duration. DA, DOPAC and HVA were assayed by high performance liquid chromatography in a group of 19 patients, distributed in two groups on the basis of the H&Y stage with a cut-off of 1.5. In these PD patients, HVA was correlated with DOPAC (R = 0,56, p < 0,01) and both HVA and DOPAC CSF levels increased in parallel with the motor impairment. More importantly, HVA correlated with motor impairment measured by the Unified Parkinson's Disease Score -III (UPDRS) (R = 0.61; p < 0.0001). The present findings showed the early alteration of the DA pre-synaptic machinery, as documented by the progressive increase of CSF HVA concentrations, which also correlated with PD motor impairment. Therefore, we suggest the potential use of measuring the CSF HVA level as a possible biomarker of PD stage changes in order to monitor the effectiveness of PD-modifying pharmacological therapies.

  13. Computed tomography, lymphography, and staging laparotomy: correlations in initial staging of Hodgkin disease

    SciTech Connect

    Castellino, R.A.; Hoppe, R.T.; Blank, N.; Young, S.W.; Neumann, C.; Rosenberg, S.A.; Kaplan, H.S.

    1984-07-01

    One hundred twenty-one patients with newly diagnosed, previously untreated Hodgkin disease underwent abdominal and pelvic computed tomographic (CT) scanning and bipedal lymphography. These studies were followed by staging laparotomy, which included biopsy of the liver, retroperitoneal and mesenteric lymph nodes, and splenectomy. Correlation of the results of the imaging studies with the histopathologic diagnoses revealed a small - but significant - increased accuracy of lymphography compared with CT in assessing the retroperitoneal lymph nodes. The theoretical advantages of CT scanning in detecting lymphomatous deposits in lymph nodes about the celiac axis and the mesentery, or in the liver and spleen, were not confirmed.

  14. [Correlation analysis of serum calcium level and cognition in the patients with Parkinson's disease].

    PubMed

    Liu, J; Zhou, X P; Zhang, L; Zhang, Q; Liu, C F; Luo, W F

    2016-11-08

    Objective: To investigate the relation between cognition and serum calcium in the patients with Parkinson's disease (PD), analyze the related factors of cognition, and evaluate the correlation of serum calcium with specific cognitive domains. Methods: A total of 77 patients with Parkinson's disease who was hospitalized in the Second Affiliated Hospital of Soochow University, from Dce 2013 to May 2015 were subjected to the cognitive, motor and depression function assessment, and the fasting blood calcium samples were collected from the PD patients and 75 normal control subjects. According to cognitive function, PD patients were divided into dementia group and without dementia group. Then the serum calcium levels of three groups and the related factors of the cognitive were analyzed by multiple linear regression. Results: (1) The level of serum calcium in PD group with dementia (2.21±0.09) mmol/L was significantly lower than the normal control group (2.30±0.09)mmol/L (P<0.001), and there was no difference between the level of serum calcium in PD group without dementia (2.27±0.13 mmol/L) and normal control group (P=0.144). The level of serum calcium in PD group with dementia was lower than PD group without dementia, and there was marked statistical significance (P=0.023). (2) In PD patients, the cognitive scores correlated with serum calcium levels, education, H-Y stages and Unified Parkinson's Disease Rating Scale (UPDRS) Ⅲ scores (P<0.05), but didn't with gender, age, disease duration, depression levels, Body Mass Index (BMI) and total equivalent levodopa doses (P>0.05). (3) In PD patients, serum calcium level correlated with the visuospatial and executive capability, calculation ability, language ability (P1=0.004; P2=0.027; P3=0.021). Conclusions: (1) There is correlation between the serum calcium and the cognitive impairment. Lower serum calcium level predicts worse cognitive scores. (2) In PD patients, the change of the cognitive function is affected by

  15. Radiotherapy as a cause of complete atrioventricular block in Hodgkin's disease. An electrophysiological-pathological correlation

    SciTech Connect

    Cohen, S.I.; Bharati, S.; Glass, J.; Lev, M.

    1981-04-01

    A 20-year-old man contracted Hodgkin's disease and was treated with mantle radiotherapy. Heart block developed 11 years later. Electrocardiograms revealed predominant atrioventricular (AV) block and occasional AV conduction. Intracardiac electrograms demonstrated that the site of AV block was above the level of the His bundle. A permanent transvenous pacemaker was implanted. Seven months later the patient died of complications from cryptococcal meningitis. Pathological study of the heart revealed marked arteriosclerosis with fibrosis of the epicardium, myocardium, and endocardium. Examination of the conduction system revealed extensive arteriolosclerosis of the sinoatrial node and its approaches. In addition, there was marked fibrosis of the approaches to the AV node, the AV bundle, and both bundle branches. There was no evidence of Hodgkin's disease. This case documents the rare occurrence of AV block due to tissue destruction by radiotherapy. There was a good correlation between block proximal to the His bundle recording site and fibrosis of the approaches to the AV node.

  16. Radiotherapy as a cause of complete atrioventricular block in Hodgkin's disease: an electrophysiological-pathological correlation

    SciTech Connect

    Cohen, S.I.; Bharati, S.; Glass, J.; Lev, M.

    1981-04-01

    A 20-year-old man contracted Hodgkin's disease and was treated with mantle radiotherapy. Heart block developed 11 years later. Electrocardiograms revealed predominant atrioventricular (AV) block and occasional AV conduction. Intracardiac electrograms demonstrated that the site of AV block was above the level of the His bundle. A permanent transvenous pacemaker was implanted. Seven months later the patient died of complications from cryptococcal meningitis. Pathological study of the heart revealed marked arteriosclerosis with fibrosis of the epicardium, myocardium, and endocardium. Examination of the conduction system revealed extensive arteriolosclerosis of the sinoatrial node and its approaches. In addition, there was marked fibrosis of the approaches to the AV node, the AV bundle, and both bundle branches. There was no evidence of Hodgkin's disease. This case documents the rare occurrence of AV block due to tissue destruction by radiotherapy. There was a good correlation between block proximal to the His bundle recording site and fibrosis of the approaches to the AV node.

  17. Correlation of mast cells in different stages of human periodontal diseases: Pilot study

    PubMed Central

    Agrawal, Raina; Gupta, Jagriti; Gupta, Krishna Kumar; Kumar, Vinod

    2016-01-01

    Aims and Objectives: The aim of this study was to evaluate and correlate the relationship between mast cells counts and different stages of human periodontal diseases. Materials and Methods: The study sample comprised 50 patients, which were divided into three groups, consisting of 10 cases of clinically healthy gingival tissues (control group) 20 cases of dental plaque-induced gingivitis with no attachment loss and 20 cases of localized chronic periodontitis (LCP) characterized by the loss of periodontal support. The samples for control group were obtained during tooth extractions for orthodontic reasons. The specimens were immediately fixed in 10% neutral buffered formalin. Conclusion: In this study, LCP cases had higher mast cell counts compared to gingivitis sites or healthy tissues. Increased mast cell counts in the progressing sites of periodontal diseases may indicate the importance of these cells in the progression of chronic periodontitis. PMID:27194868

  18. Prevalence and Correlates of Insomnia and Obstructive Sleep Apnea in Chronic Kidney Disease

    PubMed Central

    Ahmad, Shahbaj; Gupta, Manan; Gupta, Ravi; Dhyani, Mohan

    2013-01-01

    Background: Poor sleep quality, insomnia, and restless legs syndrome (RLS) and sleep apnea are common in patients with chronic kidney disease (CKD). Clinical correlates of these problems are poorly understood. Aims: This study was to find out the prevalence and correlates of insomnia and subjects with ‘high risk for obstructive sleep apnea (OSA)’ in adults with chronic kidney disease. Materials and Methods: One hundred and four adults with CKD were included. Their demographic data, details regarding kidney disease and hemodialysis (HD) were recorded. Presence of insomnia and its severity was assessed. They were screened for sleep apnea using a validated questionnaire. Results: Average age was 54.17 (± 12.96) years. 89.4% had stage 5 nephropathy and 78.8% subjects were on regular HD. Males outnumbered females. Insomnia was reported by 35.5%. Among these, 50% had chronic insomnia. Insomnia subjects had higher prevalence of diabetes (P = 0.01) and depression (P < 0.001). Fifty-one percent subjects were at “high risk for sleep apnea”. They had higher prevalence of diabetes (P < 0.001), coronary disease (P = 0.02), insomnia (P = 0.008), and experienced daytime symptoms of insomnia (P < 0.001). However, in the logistic regression, only male gender (odds ratio, OR = 13.59) and daytime symptoms of insomnia (OR = 7.34) were found to be associated with “higher risk for sleep apnea”. Conclusion: Insomnia was prevalent in CKD. Nearly half of these patients are at high risk for sleep apnea and a third of them suffer from insomnia. Hence, these patients should be screened for sleep disorders. PMID:24404542

  19. [Correlation between long-term proton pump ingibitor use, homocysteine and lipoproteins serum concentrations in patients with comorbidity of ischemic heart disease and acid peptic disease].

    PubMed

    Zharkova, A; Orlovsky, V

    2012-12-01

    Present article is devoted to the study of the correlation between vitamin B12 serum level, hyperhomocysteinaemia and dyslipidemia. During research there were discovered that the lowest vitamin B12 serum level and the highest homocysteine serum level have been registrated in associated pathology (ischemic heart disease and acid peptic disease according to long-term proton pump inhibitor use) patients. It was shown evident correlation between that changes and dyslipidemia. Тhe complex therapy that includes parenteral B12 supplementation leads to more effective correction of hyperhomocysteinaemia and dyslipidemia in patients with comorbidity of ischemic heart disease and acid peptic disease with long-term use of proton pump inhibitors.

  20. Metallothionein-1 and nitric oxide expression are inversely correlated in a murine model of Chagas disease

    PubMed Central

    Gonzalez-Mejia, Martha Elba; Torres-Rasgado, Enrique; Porchia, Leonardo M; Salgado, Hilda Rosas; Totolhua, José-Luis; Ortega, Arturo; Hernández-Kelly, Luisa Clara Regina; Ruiz-Vivanco, Guadalupe; Báez-Duarte, Blanca G; Pérez-Fuentes, Ricardo

    2014-01-01

    Chagas disease, caused by Trypanosoma cruzi, represents an endemic among Latin America countries. The participation of free radicals, especially nitric oxide (NO), has been demonstrated in the pathophysiology of seropositive individuals with T. cruzi. In Chagas disease, increased NO contributes to the development of cardiomyopathy and megacolon. Metallothioneins (MTs) are efficient free radicals scavengers of NO in vitro and in vivo. Here, we developed a murine model of the chronic phase of Chagas disease using endemic T. cruzi RyCH1 in BALB/c mice, which were divided into four groups: infected non-treated (Inf), infected N-monomethyl-L-arginine treated (Inf L-NAME), non-infected L-NAME treated and non-infected vehicle-treated. We determined blood parasitaemia and NO levels, the extent of parasite nests in tissues and liver MT-I expression levels. It was observed that NO levels were increasing in Inf mice in a time-dependent manner. Inf L-NAME mice had fewer T. cruzi nests in cardiac and skeletal muscle with decreased blood NO levels at day 135 post infection. This affect was negatively correlated with an increase of MT-I expression (r = -0.8462, p < 0.0001). In conclusion, we determined that in Chagas disease, an unknown inhibitory mechanism reduces MT-I expression, allowing augmented NO levels. PMID:24676665

  1. Pediatric Small Bowel Crohn Disease: Correlation of US and MR Enterography

    PubMed Central

    Smith, Ethan A.; Sanchez, Ramon J.; DiPietro, Michael A.; DeMatos-Maillard, Vera; Strouse, Peter J.; Darge, Kassa

    2015-01-01

    Small bowel Crohn disease is commonly diagnosed during the pediatric period, and recent investigations show that its incidence is increasing in this age group. Diagnosis and follow-up of this condition are commonly based on a combination of patient history and physical examination, disease activity surveys, laboratory assessment, and endoscopy with biopsy, but imaging also plays a central role. Ultrasonography (US) is an underutilized well-tolerated imaging modality for screening and follow-up of small bowel Crohn disease in children and adolescents. US has numerous advantages over computed tomographic (CT) enterography and magnetic resonance (MR) enterography, including low cost and no required use of oral or intravenous contrast material. US also has the potential to provide images with higher spatial resolution than those obtained at CT enterography and MR enterography, allows faster examination than does MR enterography, does not involve ionizing radiation, and does not require sedation or general anesthesia. US accurately depicts small bowel and mesenteric changes related to pediatric Crohn disease, and US findings show a high correlation with MR imaging findings in this patient population. ©RSNA, 2015 PMID:25839736

  2. Pediatric Small Bowel Crohn Disease: Correlation of US and MR Enterography.

    PubMed

    Dillman, Jonathan R; Smith, Ethan A; Sanchez, Ramon J; DiPietro, Michael A; DeMatos-Maillard, Vera; Strouse, Peter J; Darge, Kassa

    2015-01-01

    Small bowel Crohn disease is commonly diagnosed during the pediatric period, and recent investigations show that its incidence is increasing in this age group. Diagnosis and follow-up of this condition are commonly based on a combination of patient history and physical examination, disease activity surveys, laboratory assessment, and endoscopy with biopsy, but imaging also plays a central role. Ultrasonography (US) is an underutilized well-tolerated imaging modality for screening and follow-up of small bowel Crohn disease in children and adolescents. US has numerous advantages over computed tomographic (CT) enterography and magnetic resonance (MR) enterography, including low cost and no required use of oral or intravenous contrast material. US also has the potential to provide images with higher spatial resolution than those obtained at CT enterography and MR enterography, allows faster examination than does MR enterography, does not involve ionizing radiation, and does not require sedation or general anesthesia. US accurately depicts small bowel and mesenteric changes related to pediatric Crohn disease, and US findings show a high correlation with MR imaging findings in this patient population.

  3. Rainbow trout (Oncorhynchus mykiss) resistance to columnaris disease is heritable and favorably correlated with bacterial cold water disease resistance.

    PubMed

    Evenhuis, J P; Leeds, T D; Marancik, D P; LaPatra, S E; Wiens, G D

    2015-04-01

    Columnaris disease (CD), caused by Flavobacterium columnare, is an emerging disease affecting rainbow trout aquaculture. Objectives of this study were to 1) estimate heritability of CD resistance in a rainbow trout line (ARS-Fp-R) previously selected 4 generations for improved bacterial cold water disease (BCWD) resistance; 2) estimate genetic correlations among CD resistance, BCWD resistance, and growth to market BW; and 3) compare CD resistance among the ARS-Fp-R, ARS-Fp-S (selected 1 generation for increased BCWD susceptibility), and ARS-Fp-C (selection control) lines. Heritability of CD resistance was estimated using data from a waterborne challenge of 44 full-sib ARS-Fp-R families produced using a paternal half-sib mating design, and genetic correlations were estimated using these data and 5 generations of BCWD resistance, 9-mo BW (approximately 0.5 kg), and 12-mo BW (approximately 1.0 kg) data from 405 ARS-Fp-R full-sib families. The CD and BCWD challenges were initiated at approximately 52 and 84 d posthatch, or approximately 650 and 1,050 degree days (°C × d), respectively. Survival of ARS-Fp-R families ranged from 0 to 48% following CD challenge and heritability estimates were similar between CD (0.17 ± 0.09) and BCWD (0.18 ± 0.03) resistance, and the genetic correlation between these 2 traits was favorable (0.35 ± 0.25). Genetic correlations were small and antagonistic (-0.15 ± 0.08 to -0.19 ± 0.24) between the 2 resistance traits and 9- and 12-mo BW. Two challenges were conducted in consecutive years to compare CD resistance among ARS-Fp-R, ARS-Fp-C, and ARS-Fp-S families. In the first challenge, ARS-Fp-R families (83% survival) had greater CD resistance than ARS-Fp-C (73.5%; P = 0.02) and ARS-Fp-S (68%; P < 0.001) families, which did not differ (P = 0.16). In the second challenge, using an approximately 2.5-fold greater challenge dose, ARS-Fp-R families exhibited greater CD resistance (56% survival) than ARS-Fp-S (38% survival; P = 0.02) families

  4. Non linear approach to study the dynamics of neurodegenerative diseases by Multifractal Detrended Cross-correlation Analysis-A quantitative assessment on gait disease

    NASA Astrophysics Data System (ADS)

    Dutta, Srimonti; Ghosh, Dipak; Samanta, Shukla

    2016-04-01

    This paper studies the human gait pattern of normal people and patients suffering from Parkinson's disease using the MFDXA (Multifractal Detrended Cross-correlation Analysis) methodology. The auto correlation and cross correlation of the time series of the total force under the left foot and right foot were studied. The study reveals that the degree of multifractality (W) and degree of correlation (γ) are generally more for normal patients than the diseased set. It is also observed that the values of W and γ are nearly same for left foot and right. It is also observed that the study of autocorrelation alone is not sufficient, cross correlations should also be studied to get a better concept of neurodegenerative diseases.

  5. Grey and White Matter Clinico-Anatomical Correlates of Disinhibition in Neurodegenerative Disease

    PubMed Central

    Santillo, Alexander Frizell; Lundblad, Karl; Nilsson, Markus; Landqvist Waldö, Maria; van Westen, Danielle; Lätt, Jimmy; Blennow Nordström, Erik; Vestberg, Susanna; Lindberg, Olof; Nilsson, Christer

    2016-01-01

    Disinhibition is an important symptom in neurodegenerative diseases. However, the clinico-anatomical underpinnings remain controversial. We explored the anatomical correlates of disinhibition in neurodegenerative disease using the perspective of grey and white matter imaging. Disinhibition was assessed with a neuropsychological test and a caregiver information-based clinical rating scale in 21 patients with prefrontal syndromes due to behavioural variant frontotemporal dementia (n = 12) or progressive supranuclear palsy (n = 9), and healthy controls (n = 25). Cortical thickness was assessed using the Freesurfer software on 3T MRI data. The integrity of selected white matter tracts was determined by the fractional anisotropy (FA) from Diffusion Tensor Imaging. Disinhibition correlated with the cortical thickness of the right parahippocampal gyrus, right orbitofrontal cortex and right insula and the FA of the right uncinate fasciculus and right anterior cingulum. Notably, no relationship was seen with the thickness of ventromedial prefrontal cortex. Our results support an associative model of inhibitory control, distributed in a medial temporal lobe-insular-orbitofrontal network, connected by the intercommunicating white matter tracts. This reconciles some of the divergences among previous studies, but also questions the current conceptualisation of the “prefrontal” syndrome and the central role attributed to the ventromedial prefrontal cortex in inhibitory control. PMID:27723823

  6. Cardiac Magnetic Resonance-Verified Myocardial Fibrosis in Chagas Disease: Clinical Correlates and Risk Stratification

    PubMed Central

    Uellendahl, Marly; de Siqueira, Maria Eduarda Menezes; Calado, Eveline Barros; Kalil-Filho, Roberto; Sobral, Dário; Ribeiro, Clébia; Oliveira, Wilson; Martins, Silvia; Narula, Jagat; Rochitte, Carlos Eduardo

    2016-01-01

    Background Chagas disease (CD) is an important cause of heart failure and mortality, mainly in Latin America. This study evaluated the morphological and functional characteristics of the heart as well the extent of myocardial fibrosis (MF) in patients with CD by cardiac magnetic resonance (CMR). The prognostic value of MF evaluated by myocardial-delayed enhancement (MDE) was compared with that via Rassi score. Methods This study assessed 39 patients divided into 2 groups: 28 asymptomatic patients as indeterminate form group (IND); and symptomatic patients as Chagas Heart Disease (CHD) group. All patients underwent CMR using the techniques of cine-MRI and MDE, and the amount of MF was compared with the Rassi score. Results Regarding the morphological and functional analysis, significant differences were observed between both groups (p < 0.001). Furthermore, there was a strong correlation between the extent of MF and the Rassi score (r = 0.76). Conclusions CMR is an important technique for evaluating patients with CD, stressing morphological and functional differences in all clinical presentations. The strong correlation with the Rassi score and the extent of MF detected by CMR emphasizes its role in the prognostic stratification of patients with CD. PMID:27982271

  7. Neuropsychological and Emotional Correlates of Personality Traits in Parkinson’s Disease

    PubMed Central

    Koerts, Janneke; Tucha, Lara; Leenders, Klaus L.; Tucha, Oliver

    2013-01-01

    Parkinson’s disease (PD) is, apart from the well-known motor symptoms, also characterized by neuropsychological and emotional disturbances. However, patients also often present with a personality profile of low Novelty Seeking and high Harm Avoidance. This profile can be identified as the disease emerges, which raises the question whether these traits correlate with more fundamental neuropsychological and emotional disturbances. This study determined the neuropsychological and emotional correlates of Novelty Seeking, Harm Avoidance and two other personality traits that are often considered in PD, i.e. Reward Dependence and Persistence. Forty-three patients and 25 healthy participants were assessed with the Temperament and Character Inventory, a symptoms of depression questionnaire and neuropsychological tests. PD patients showed a higher Harm Avoidance than healthy participants, which was predicted by symptoms of depression. Groups did not differ regarding Novelty Seeking, Reward Dependence and Persistence. While cognitive flexibility was a predictor of Reward Dependence, Persistence was predicted by divergent thinking and inhibition. Novelty Seeking was not predicted by cognition or emotion. In conclusion, cognition and emotion are selectively related to personality traits in PD. Whereas Harm Avoidance covaries with emotional symptoms, Persistence and Reward Dependence are related to cognition. Alterations in personality, cognition and emotion in PD are thus not independent from each other. PMID:23242356

  8. New global map of Crohn's disease: Genetic, environmental, and socioeconomic correlations.

    PubMed

    Economou, Michael; Pappas, Georgios

    2008-05-01

    Seventy-five years after the initial characterization of Crohn's disease (CD), much remains obscure about its etiology. The authors sought to evaluate the incidence trends of the last 25 years worldwide, and the existence of potential correlations with genetic, environmental, and socioeconomic factors that could be etiologically implicated in the pathogenesis of CD. Relevant medical literature for individual countries on the incidence of CD, on the incidence of associated genetic mutations, and on the incidence of suggested etiologic infectious agents such as Mycobacterium avium paratuberculosis were retrieved from published medical literature, reports from relevant international congresses, and through official reports from national health authorities. Increasing trends have been observed almost worldwide, with a broad north-south gradient still prevailing in Europe. Distinct regions of New Zealand, Canada, Scotland, France, the Netherlands, and Scandinavia represent the highest incidence areas. Industrialized status and affluence are the common denominators between endemic areas, but are too broad as terms to strongly indicate any particular etiological role. The increasing trends observed in Asia still account for a low prevalence of the disease and may represent increased detection and diagnostic ability of local health systems. Genetic associations are variably reproduced worldwide, in a manner inconsistent with a strong etiologic relationship. Data on paratuberculosis incidence are scarce, and the existing ones are ambivalent regarding an even indirect correlation between CD and an infectious trigger.

  9. High Mobility Group Box Protein-1 correlates with renal function in chronic kidney disease (CKD).

    PubMed

    Bruchfeld, Annette; Qureshi, Abdul Rashid; Lindholm, Bengt; Barany, Peter; Yang, Lihong; Stenvinkel, Peter; Tracey, Kevin J

    2008-01-01

    Chronic kidney disease (CKD) is associated with inflammation and malnutrition and carries a markedly increased risk of cardiovascular disease (CVD). High Mobility Group Box Protein-1 (HMGB-1) is a 30-kDa nuclear and cytosolic protein known as a transcription and growth factor, recently identified as a proinflammatory mediator of tissue injury. Recent data implicates HMGB-1 in endotoxin lethality, rheumatoid arthritis, and atherosclerosis. The aim of this post-hoc, cross-sectional study was to determine whether HMGB-1 serum levels are elevated in CKD patients. The study groups were categorized as follows: 110 patients starting dialysis defined as CKD 5; 67 patients with moderately to severely reduced renal function or CKD 3-4; and 48 healthy controls. High-sensitivity C-reactive-protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor (TNF), serum-albumin (S-albumin), hemoglobin A(1c) (HbA(1c)), hemoglobin, subjective global nutritional assessment (SGA), and glomerular filtration rate (GFR) were analyzed. Kruskal-Wallis test was used to compare groups and Spearman's rank correlation test was used for continuous variables. HMGB-1, measured by Western blot, was significantly (P < 0.001) elevated in CKD 5 (146.7 +/- 58.6 ng/mL) and CKD 3-4 (85.6 +/- 31.8) compared with controls (10.9 +/- 10.5). HMGB-1 levels were correlated positively with TNF (Rho = 0.52; P < 0.001), hs-CRP (Rho = 0.38; P < 0.001), IL-6 (Rho = 0.30; P < 0.001), HbA(1c) (Rho = 0.14; P = 0.02) and SGA (Rho = 0.21; P = 0.002) and negatively correlated with GFR (Rho = -0.69; P = 0.0001), Hb (Rho = -0.60; P < 0.001), S-albumin (Rho = -0.31; P < 0.001). The current study has revealed that HMGB-1 is elevated significantly in CKD patients and correlates with GFR as well as markers of inflammation and malnutrition. Future studies may delineate whether HMGB-1 is also a marker of disease activity and severity as well as a predictor of outcome in CKD.

  10. Clinical Correlations With Lewy Body Pathology in LRRK2-Related Parkinson Disease

    PubMed Central

    Kalia, Lorraine V.; Lang, Anthony E.; Hazrati, Lili-Naz; Fujioka, Shinsuke; Wszolek, Zbigniew K.; Dickson, Dennis W.; Ross, Owen A.; Van Deerlin, Vivianna M.; Trojanowski, John Q.; Hurtig, Howard I.; Alcalay, Roy N.; Marder, Karen S.; Clark, Lorraine N.; Gaig, Carles; Tolosa, Eduardo; Ruiz-Martínez, Javier; Marti-Masso, Jose F.; Ferrer, Isidre; de Munain, Adolfo López; Goldman, Samuel M.; Schüle, Birgitt; Langston, J. William; Aasly, Jan O.; Giordana, Maria T.; Bonifati, Vincenzo; Puschmann, Andreas; Canesi, Margherita; Pezzoli, Gianni; De Paula, Andre Maues; Hasegawa, Kazuko; Duyckaerts, Charles; Brice, Alexis; Stoessl, A. Jon; Marras, Connie

    2015-01-01

    IMPORTANCE Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of genetic Parkinson disease (PD) known to date. The clinical features of manifesting LRRK2 mutation carriers are generally indistinguishable from those of patients with sporadic PD. However, some PD cases associated with LRRK2 mutations lack Lewy bodies (LBs), a neuropathological hallmark of PD. We investigated whether the presence or absence of LBs correlates with different clinical features in LRRK2-related PD. OBSERVATIONS We describe genetic, clinical, and neuropathological findings of 37 cases of LRRK2-related PD including 33 published and 4 unpublished cases through October 2013. Among the different mutations, the LRRK2 p.G2019S mutation was most frequently associated with LB pathology. Nonmotor features of cognitive impairment/dementia, anxiety, and orthostatic hypotension were correlated with the presence of LBs. In contrast, a primarily motor phenotype was associated with a lack of LBs. CONCLUSIONS AND RELEVANCE To our knowledge, this is the first report of clinicopathological correlations in a series of LRRK2-related PD cases. Findings from this selected group of patients with PD demonstrated that parkinsonian motor features can occur in the absence of LBs. However, LB pathology in LRRK2-related PD may be a marker for a broader parkinsonian symptom complex including cognitive impairment. PMID:25401511

  11. Oscillatory pallidal local field potential activity inversely correlates with limb dyskinesias in Parkinson's disease.

    PubMed

    Silberstein, Paul; Oliviero, Antonio; Di Lazzaro, Vincenzo; Insola, Angelo; Mazzone, Paolo; Brown, Peter

    2005-08-01

    Levodopa induced dyskinesias (LIDs) are poorly understood and yet are a major cause of disability in Parkinson's disease (PD). The activity of neurons in the basal ganglia of patients with PD tends to be strongly synchronized at frequencies under 30 Hz, leading to oscillatory local field potentials (LFPs). As dopaminergic therapy acutely suppresses this synchronization, we investigated whether this suppression may contribute to LIDs. Accordingly, we sought an inverse correlation between oscillatory synchronization and dyskinesia activity across time. To this end, we recorded pallidal LFPs in two Parkinsonian subjects exhibiting LIDs following surgery for deep brain stimulation. We correlated LFP power with simultaneously recorded EMG from the dyskinetic contralateral upper limb. We found highly significant inverse correlations between the oscillatory LFP activity under 30 Hz and dyskinetic EMG (maximum r = -0.65, P < 0.001 and r = -0.33, P < 0.001 for activities over 13-30 Hz in each subject). The inverse relationship between oscillatory pallidal LFP activity and dyskinetic EMG was maintained over time periods of a few seconds and was focal. This observation links the suppression of oscillatory synchronization in the pallidum with dyskinetic muscle activity in PD.

  12. NF-κB activity is inversely correlated to RNF11 expression in Parkinson's disease.

    PubMed

    Pranski, Elaine; Van Sanford, Carson D; Dalal, Nirjari; Orr, Adam L; Karmali, Dipan; Cooper, Deborah S; Gearing, Marla; Lah, James J; Levey, Allan I; Betarbet, Ranjita

    2013-06-28

    RING finger protein 11 (RNF11), a negative regulator of NF-κB signaling pathway, colocalizes with α-synuclein and is sequestered in Lewy bodies in Parkinson's disease (PD). Since persistent NF-κB activation is reported in PD, in this report we investigated if RNF11 expression level is correlated to activated NF-κB in PD. We examined RNF11 expression levels in correlation to phospho-p65, a marker for activated NF-κB, in control and PD brain tissue from cerebral cortex. In addition we performed double immunofluorescence labeling experiments to confirm this correlation. Our investigations demonstrated that the neuronal RNF11 expression was down-regulated in PD and was usually associated with increased expression of phospho-p65. Double labeling confirmed that loss of neuronal RNF11 was linked to increased phospho-p65 expression, suggesting that persistent presence of NF-κB activation could be due to decreased levels of its negative regulator. Our data exemplifies the relevance of RNF11 and persistent NF-κB activation in PD.

  13. Neuroanatomical correlates of verbal fluency in early Alzheimer's disease and normal aging.

    PubMed

    Rodríguez-Aranda, Claudia; Waterloo, Knut; Johnsen, Stein Harald; Eldevik, Petter; Sparr, Sigurd; Wikran, Gry C; Herder, Marit; Vangberg, Torgil Riise

    2016-01-01

    Verbal fluency (VF) impairments occur early in Alzheimer's disease (AD) and to a lesser extent also in normal aging. However, the neural underpinnings of these impairments are not fully understood. The present study evaluated whether VF impairments in early AD and normal aging rely upon common or different neuroanatomical correlates. We examined the association between VF performance and brain structure in 18 mild AD patients and 24 healthy elderly. Linear regressions were performed between accuracy and time intervals in VF scores and structural measurements of cerebral gray matter (GM) and white matter (WM) using MRI. Results showed that semantic VF correlated exclusively with GM in cerebellum, left temporal fusiform cortex, and WM in uncinate fasciculus, inferior fronto-occipital fasciculus and corpus callosum. Phonemic VF showed unique associations between intervals and WM in left-hemisphere tracts. The association between GM in hippocampus, subcortical structures and semantic accuracy differentiated patients from controls. Results showed that VF impairments are primarily associated with same structural brain changes in AD as in healthy elderly but at exaggerated levels. However, specific VF deficiencies and their underlying neural correlates exist and these clearly differentiate the initial stages of AD.

  14. White-Matter Changes Correlate with Cognitive Functioning in Parkinson’s Disease

    PubMed Central

    Theilmann, Rebecca J.; Reed, Jason D.; Song, David D.; Huang, Mingxiong X.; Lee, Roland R.; Litvan, Irene; Harrington, Deborah L.

    2013-01-01

    Diffusion tensor imaging (DTI) findings from emerging studies of cortical white-matter integrity in Parkinson’s disease (PD) without dementia are inconclusive. When white-matter changes have been found, their relationship to cognitive functioning in PD has not been carefully investigated. To better characterize changes in tissue diffusivity and to understand their functional significance, the present study conducted DTI in 25 PD patients without dementia and 26 controls of similar ages. An automated tract-based DTI method was used. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were analyzed. Neuropsychological measures of executive functioning (working memory, verbal fluency, cognitive flexibility, inhibitory control) and visuospatial ability were then correlated with regions of interest that showed abnormal diffusivity in the PD group. We found widespread reductions in FA and increases in MD in the PD group relative to controls. These changes were predominantly related to an increase in RD. Increased AD in the PD group was limited to specific frontal tracks of the right hemisphere, possibly signifying more significant tissue changes. Motor symptom severity did not correlate with FA. However, different measures of executive functioning and visuospatial ability correlated with FA in different segments of tracts, which contain fiber pathways to cortical regions that are thought to support specific cognitive processes. The findings suggest that abnormal tissue diffusivity may be sensitive to subtle cognitive changes in PD, some of which may be prognostic of future cognitive decline. PMID:23630517

  15. Genetic correlates of behavioral endophenotypes in Alzheimer disease: role of COMT, 5-HTTLPR and APOE polymorphisms.

    PubMed

    Borroni, B; Grassi, M; Agosti, C; Costanzi, C; Archetti, S; Franzoni, S; Caltagirone, C; Di Luca, M; Caimi, L; Padovani, A

    2006-11-01

    Several studies have been conducted to understand the genetic correlates of Alzheimer disease (AD)-related behavioral and psychological symptoms in dementia (BPSD). However, given that BPSD rarely occur in isolation, it has been suggested that targeting BPSD individually is too narrow of an approach if one wants to accurately define all the associated risk factors. To date, we know of no work on genetic polymorphisms related to behavioral endophenotypes in AD. The present study sought to evaluate the relationship between such behavioral endophenotypes in AD and genetic variations in dopamine- or serotonin-related genes, such as catechol-O-methyltransferase (COMT) or 5-HTT gene-linked promoter region (5-HTTLPR), and apolipoprotein E (APOE). Among 232 AD patients who underwent clinical and neuropsychological examination, a behavioral and psychiatric evaluation, and genotyping at COMT, 5-HTTPLR, and APOE; 66.4% showed more than one behavioral symptom. By Principal Component Analysis of Neuropsychiatric Inventory (NPI) symptoms four endophenotypes were identified, these were termed "psychosis", "moods", "apathy", and "frontal". Modeling NPI symptom-endophenotype-genotype relationships, and taking into account possible confounds (i.e. demographic characteristics, comorbidities, concomitant pharmacological treatments, and disease severity) by latent variable models, COMT and 5-HTTLPR genetic variations correlated with "frontal" and "psychosis" endophenotypes. APOE genotype did not correlate with any endophenotype. These findings suggest that the possibility of identifying distinct phenotypes on a genetic basis among AD patients exists, and suggest that clustering of BPSD into endophenotypes might provide a new strategy for guiding future research on this issue.

  16. Cognitive deficits in Machado-Joseph disease correlate with hypoperfusion of visual system areas.

    PubMed

    Braga-Neto, Pedro; Dutra, Lívia Almeida; Pedroso, José Luiz; Felício, André C; Alessi, Helena; Santos-Galduroz, Ruth F; Bertolucci, Paulo Henrique F; Castiglioni, Mário Luiz V; Bressan, Rodrigo Affonseca; de Garrido, Griselda Esther Jara; Barsottini, Orlando Graziani Povoas; Jackowski, Andrea

    2012-12-01

    Cognitive and olfactory impairments have previously been demonstrated in patients with spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD)-SCA3/MJD. We investigated changes in regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT) imaging in a cohort of Brazilian patients with SCA3/MJD. The aim of the present study was to evaluate the correlation among rCBF, cognitive deficits, and olfactory dysfunction in SCA3/MJD. Twenty-nine genetically confirmed SCA3/MJD patients and 25 control subjects were enrolled in the study. The severity of cerebellar symptoms was measured using the International Cooperative Ataxia Rating Scale and the Scale for the Assessment and Rating of Ataxia. Psychiatric symptoms were evaluated by the Hamilton Anxiety Scale and Beck Depression Inventory. The neuropsychological assessment consisted of Spatial Span, Symbol Search, Picture Completion, the Stroop Color Word Test, Trail Making Test (TMT), and Phonemic Verbal Fluency. Subjects were also submitted to odor identification evaluation using the 16-item Sniffin' Sticks. SPECT was performed using ethyl cysteine dimer labeled with technetium-99m. SCA3/MJD patients showed reduced brain perfusion in the cerebellum, temporal, limbic, and occipital lobes compared to control subjects (pFDR <0.001). A significant positive correlation was found between the Picture Completion test and perfusion of the left parahippocampal gyrus and basal ganglia in the patient group as well as a negative correlation between the TMT part A and bilateral thalamus perfusion. The visuospatial system is affected in patients with SCA3/MJD and may be responsible for the cognitive deficits seen in this disease.

  17. Thoracic involvement in Behçet's disease and its correlation with multiple parameters.

    PubMed

    Gunen, H; Evereklioglu, C; Kosar, F; Er, H; Kizkin, O

    2000-01-01

    In Behçet's disease (BD), controversy has existed over the incidence of thoracic involvement, which may be a direct threat to the patient's life. The aim of this study is to evaluate the incidence of thoracic involvement in BD and its correlation with the number of diagnostic BD criteria of The International Study Group (ISG), gender, disease duration, and the presence of symptoms. Forty-two BD patients, who had consecutively applied to different clinics in Turgut Ozal Medical Center Research Hospital, were included in the study. They were either newly diagnosed or already under treatment. All patients were examined by standard chest roentgenogram, spirometry, and thorax CT. Perfusion scintigraphies were obtained in patients with thoracic involvement. Thoracic pathologic conditions were found in five patients (11.9%). All thoracic pathologic conditions appeared in patients with at least four diagnostic criteria (26 patients) of the ISG for BD. In this subgroup, the rate of thoracic involvement was 19.2%. Also, 25% of the patients with pulmonary symptoms (12 patients) had thoracic lesions. Gender and the duration of the disease did not correlate with thoracic involvement. Our findings suggest that the rate of thoracic involvement in BD is greater than is generally believed. An increased number of diagnostic BD criteria of the ISG may indicate other organ system involvement and an increased risk of thoracic pathosis. All BD patients with at least four diagnostic criteria or any pulmonary symptoms should be evaluated for thoracic involvement, which is a major menace to life and necessitates early intervention.

  18. S1PR1 expression correlates with inflammatory responses to Newcastle disease virus infection.

    PubMed

    Li, Yaling; Xie, Peng; Sun, Minhua; Xiang, Bin; Kang, Yinfeng; Gao, Pei; Zhu, Wenxian; Ning, Zhangyong; Ren, Tao

    2016-01-01

    Newcastle disease virus (NDV) is the causative agent of Newcastle disease, which is characterized by inflammatory pathological changes in the organs of chickens. The inflammatory response to this disease has not been well characterized. Previous reports showed that the sphingosine-1-phosphate-1 receptor (S1PR1), a G protein-coupled receptor, is important to the activation of inflammatory responses. To understand better the viral pathogenesis and host inflammatory response, we analyzed S1PR1 expression during NDV infection. We observed a direct correlation between chicken embryo fibroblast (CEF) cellular inflammatory responses and S1PR1 expression. Virulent NDV-infected CEF cells also had elevated levels of pro-inflammatory cytokines (IL-1β, IL-6 and IL-18). When S1PR1 was inhibited by using the specific antagonist W146, pro-inflammatory cytokine production declined. Overexpression of S1PR1 resulted in increased virus-induced IL-1β production. S1PR1 expression levels did not impact significantly NDV replication. These findings highlight the important role of S1PR1 in inflammatory responses in NDV infection.

  19. Discriminative Learning for Alzheimer's Disease Diagnosis via Canonical Correlation Analysis and Multimodal Fusion

    PubMed Central

    Lei, Baiying; Chen, Siping; Ni, Dong; Wang, Tianfu

    2016-01-01

    To address the challenging task of diagnosing neurodegenerative brain disease, such as Alzheimer's disease (AD) and mild cognitive impairment (MCI), we propose a novel method using discriminative feature learning and canonical correlation analysis (CCA) in this paper. Specifically, multimodal features and their CCA projections are concatenated together to represent each subject, and hence both individual and shared information of AD disease are captured. A discriminative learning with multilayer feature hierarchy is designed to further improve performance. Also, hybrid representation is proposed to maximally explore data from multiple modalities. A novel normalization method is devised to tackle the intra- and inter-subject variations from the multimodal data. Based on our extensive experiments, our method achieves an accuracy of 96.93% [AD vs. normal control (NC)], 86.57 % (MCI vs. NC), and 82.75% [MCI converter (MCI-C) vs. MCI non-converter (MCI-NC)], respectively, which outperforms the state-of-the-art methods in the literature. PMID:27242506

  20. Genotype-phenotype correlations in von Hippel-Lindau (VHL) disease: Predisposition to pheochromocytoma

    SciTech Connect

    Maher, E.R.; Crossey, P.A.; Richards, F.M.

    1994-09-01

    VHL disease is a dominantly inherited familial cancer syndrome predisposing to a variety of neoplasms, most frequently retinal and CNS haemangioblastoma, renal cell carcinoma, and pheochromocytoma. Marked interfamilial differences in predisposition to pheochromocytoma are recognized. We identified germline mutations in 85 unrelated VHL disease patients (22 large germline deletions, 44 different intragenic mutations: 21 missense, 6 nonsense, 16 deletions or insertions, 1 splice donor site mutation), and correlated this information with phenotype in 65 kindreds. Large deletions or intragenic mutations predicted to cause a truncated protein were found in 36 of 53 families without pheochromocytoma but only 2 of 12 families with pheochromocytoma ({chi}{sup 2}=12.33 p<0.01). Of 12 families with pheochromocytoma, 10 had missense mutations compared to 13 of 53 kindreds without pheochromocytoma ({chi}{sup 2}=12.33 p<0.001). 5% of kindreds with large deletions or intragenic mutations predicted to cause a truncated protein were pheochromocytoma positive, compared to 43% of kindreds with misense mutations. In particular, substitution of an arginine at codon 238 (Arg{yields}Trp or Arg{yields}Gln) was associated with a high risk (62%) of pheochromocytoma. The identification of germline mutations in VHL disease not only allows presymptomatic diagnosis, but can also indicate the risk of pheochromocytoma. In addition these results provide a basis for screening for VHL gene mutations in patients with familial or sporadic pheochromocytoma. To date, VHL gene mutations have been identified in 2 families with familial pheochromocytoma.

  1. Multimodal Image Analysis in Alzheimer's Disease via Statistical Modelling of Non-local Intensity Correlations.

    PubMed

    Lorenzi, Marco; Simpson, Ivor J; Mendelson, Alex F; Vos, Sjoerd B; Cardoso, M Jorge; Modat, Marc; Schott, Jonathan M; Ourselin, Sebastien

    2016-04-11

    The joint analysis of brain atrophy measured with magnetic resonance imaging (MRI) and hypometabolism measured with positron emission tomography with fluorodeoxyglucose (FDG-PET) is of primary importance in developing models of pathological changes in Alzheimer's disease (AD). Most of the current multimodal analyses in AD assume a local (spatially overlapping) relationship between MR and FDG-PET intensities. However, it is well known that atrophy and hypometabolism are prominent in different anatomical areas. The aim of this work is to describe the relationship between atrophy and hypometabolism by means of a data-driven statistical model of non-overlapping intensity correlations. For this purpose, FDG-PET and MRI signals are jointly analyzed through a computationally tractable formulation of partial least squares regression (PLSR). The PLSR model is estimated and validated on a large clinical cohort of 1049 individuals from the ADNI dataset. Results show that the proposed non-local analysis outperforms classical local approaches in terms of predictive accuracy while providing a plausible description of disease dynamics: early AD is characterised by non-overlapping temporal atrophy and temporo-parietal hypometabolism, while the later disease stages show overlapping brain atrophy and hypometabolism spread in temporal, parietal and cortical areas.

  2. Correlation between enzyme activity and substrate storage in a cell culture model system for Gaucher disease.

    PubMed

    Schueler, U H; Kolter, T; Kaneski, C R; Zirzow, G C; Sandhoff, K; Brady, R O

    2004-01-01

    Gaucher disease, the most common sphingolipidosis, is caused by a decreased activity of glucosylceramide beta-glucosidase, resulting in the accumulation of glucosylceramide in macrophage-derived cells known as Gaucher cells. Much of the storage material is thought to originate from the turnover of cell membranes, such as phagocytosed red and white blood cells. In this study, an in vitro model of Gaucher disease was developed by treating the murine macrophage cell line J774 with a specific inhibitor of glucosylceramide beta-glucosidase, conduritol B-epoxide, and feeding red blood cell ghosts, in order to mimic the disease state. It was found in this model system that glucosylceramide beta-glucosidase activity could be reduced to about 11-15% of the normal control level before increased storage of glucosylceramide occurred. This in vitro system allows insight into the correlation between enzyme activity and lipid storage as predicted by the theory of residual enzyme activity that was proposed by Conzelmann and Sandhoff.

  3. Some anamnestic and clinical parameters correlated to longterm pulmonary hypertension development in patients with chronic obstructive lung disease.

    PubMed

    Mazzola, C; Ghiringhelli, G; Caspani, F; Cavallaro, G F

    1976-01-01

    A statistical correlation between anamnestic and hemodynamic data was performed in 40 patients with chronic obstructive lung disease and pulmonary hypertension at rest. Cardiopulmonary hemodynamic performance was significantly correlated with some of the assessed parameters, especially duration of illness and symptoms generally related with airway obstruction as dyspnea, cough and sputum.

  4. Neuronal and Physiological Correlation to Hemodynamic Resting-State Fluctuations in Health and Disease

    PubMed Central

    Murphy, Matthew C.; Kim, Seong-Gi

    2014-01-01

    Abstract Low-frequency, spatially coherent fluctuations present in functional magnetic resonance imaging time series have had a tremendous impact on brain connectomics. This work aims to explore the degree with which hemodynamic connectivity is associated with neuronal, metabolic, and vascular connectivity measures. For this purpose, GCaMP and nontransgenic mice were used to image neuronal activity and oxidative metabolism activity, respectively, along with blood-oxygenation- and cerebral blood volume (CBV)–sensitive hemodynamic changes from the same animals. Although network clusters calculated using either GCaMP (neuronal activity) or optical imaging of intrinsic signal (OIS)–BOLD (blood oxygenation) data did not exhibit strong spatial similarity, the strengths of node-to-node connectivity measured with these modalities were strongly correlated with one another. This finding suggests that hemodynamic connectivity as measured by blood oxygenation measurements, such as functional connectivity magnetic resonance imaging, is a valuable surrogate for the underlying neuronal connectivity. In nontransgenic animals, greater connectivity correlation was observed between tissue oxidative metabolism (flavoprotein autofluorescence imaging [FAI]) and blood oxygenation measurements, suggesting that metabolic contributions to hemodynamic signals are likely responsible for its significant correlation with neuronal connectivity. Lastly, a mouse model of Alzheimer's disease was used to explore the source of decreases in connectivity reported in these mice, a finding that is thought to be associated with amyloid load-driven metabolic decline. The intercluster connectivity measured by metabolic-sensitive measurements (FAI and OIS-BOLD) was maintained while vascular-only signals (OIS-CBV) provided negligible correlation. Therefore, metabolism-sensitive measurements as used in this work are better positioned to capture changes in neuronal connectivity, such that decreases in

  5. Genome-wide associations for birth weight and correlations with adult disease.

    PubMed

    Horikoshi, Momoko; Beaumont, Robin N; Day, Felix R; Warrington, Nicole M; Kooijman, Marjolein N; Fernandez-Tajes, Juan; Feenstra, Bjarke; van Zuydam, Natalie R; Gaulton, Kyle J; Grarup, Niels; Bradfield, Jonathan P; Strachan, David P; Li-Gao, Ruifang; Ahluwalia, Tarunveer S; Kreiner, Eskil; Rueedi, Rico; Lyytikäinen, Leo-Pekka; Cousminer, Diana L; Wu, Ying; Thiering, Elisabeth; Wang, Carol A; Have, Christian T; Hottenga, Jouke-Jan; Vilor-Tejedor, Natalia; Joshi, Peter K; Boh, Eileen Tai Hui; Ntalla, Ioanna; Pitkänen, Niina; Mahajan, Anubha; van Leeuwen, Elisabeth M; Joro, Raimo; Lagou, Vasiliki; Nodzenski, Michael; Diver, Louise A; Zondervan, Krina T; Bustamante, Mariona; Marques-Vidal, Pedro; Mercader, Josep M; Bennett, Amanda J; Rahmioglu, Nilufer; Nyholt, Dale R; Ma, Ronald C W; Tam, Claudia H T; Tam, Wing Hung; Ganesh, Santhi K; van Rooij, Frank J A; Jones, Samuel E; Loh, Po-Ru; Ruth, Katherine S; Tuke, Marcus A; Tyrrell, Jessica; Wood, Andrew R; Yaghootkar, Hanieh; Scholtens, Denise M; Paternoster, Lavinia; Prokopenko, Inga; Kovacs, Peter; Atalay, Mustafa; Willems, Sara M; Panoutsopoulou, Kalliope; Wang, Xu; Carstensen, Lisbeth; Geller, Frank; Schraut, Katharina E; Murcia, Mario; van Beijsterveldt, Catharina E M; Willemsen, Gonneke; Appel, Emil V R; Fonvig, Cilius E; Trier, Caecilie; Tiesler, Carla M T; Standl, Marie; Kutalik, Zoltán; Bonàs-Guarch, Sílvia; Hougaard, David M; Sánchez, Friman; Torrents, David; Waage, Johannes; Hollegaard, Mads V; de Haan, Hugoline G; Rosendaal, Frits R; Medina-Gomez, Carolina; Ring, Susan M; Hemani, Gibran; McMahon, George; Robertson, Neil R; Groves, Christopher J; Langenberg, Claudia; Luan, Jian'an; Scott, Robert A; Zhao, Jing Hua; Mentch, Frank D; MacKenzie, Scott M; Reynolds, Rebecca M; Lowe, William L; Tönjes, Anke; Stumvoll, Michael; Lindi, Virpi; Lakka, Timo A; van Duijn, Cornelia M; Kiess, Wieland; Körner, Antje; Sørensen, Thorkild I A; Niinikoski, Harri; Pahkala, Katja; Raitakari, Olli T; Zeggini, Eleftheria; Dedoussis, George V; Teo, Yik-Ying; Saw, Seang-Mei; Melbye, Mads; Campbell, Harry; Wilson, James F; Vrijheid, Martine; de Geus, Eco J C N; Boomsma, Dorret I; Kadarmideen, Haja N; Holm, Jens-Christian; Hansen, Torben; Sebert, Sylvain; Hattersley, Andrew T; Beilin, Lawrence J; Newnham, John P; Pennell, Craig E; Heinrich, Joachim; Adair, Linda S; Borja, Judith B; Mohlke, Karen L; Eriksson, Johan G; Widén, Elisabeth; Kähönen, Mika; Viikari, Jorma S; Lehtimäki, Terho; Vollenweider, Peter; Bønnelykke, Klaus; Bisgaard, Hans; Mook-Kanamori, Dennis O; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G; Pisinger, Charlotta; Pedersen, Oluf; Power, Christine; Hyppönen, Elina; Wareham, Nicholas J; Hakonarson, Hakon; Davies, Eleanor; Walker, Brian R; Jaddoe, Vincent W V; Järvelin, Marjo-Riitta; Grant, Struan F A; Vaag, Allan A; Lawlor, Debbie A; Frayling, Timothy M; Smith, George Davey; Morris, Andrew P; Ong, Ken K; Felix, Janine F; Timpson, Nicholas J; Perry, John R B; Evans, David M; McCarthy, Mark I; Freathy, Rachel M

    2016-10-13

    Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW (P < 5 × 10(-8)). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (Rg = -0.22, P = 5.5 × 10(-13)), T2D (Rg = -0.27, P = 1.1 × 10(-6)) and coronary artery disease (Rg = -0.30, P = 6.5 × 10(-9)). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P = 1.9 × 10(-4)). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.

  6. Correlates of dietary energy sources with cardiovascular disease risk markers in Mexican school-age children.

    PubMed

    Perichart-Perera, Otilia; Balas-Nakash, Margie; Rodríguez-Cano, Ameyalli; Muñoz-Manrique, Cinthya; Monge-Urrea, Adriana; Vadillo-Ortega, Felipe

    2010-02-01

    Dietary and lifestyle changes in Mexico have been linked to an increase in chronic diseases such as obesity and cardiovascular disease. Important dietary changes such as an increase in the consumption of energy-dense foods (high in oils, animal or processed fats, and sugars) have been recently reported. The objective of this study was to identify how key dietary energy sources correlated with other indexes of cardiovascular disease in a Mexican school-age population. From 2004 to 2006, a convenience sample (n=228) of 9- to 13-year-olds, 48.2% girls and 51.8% boys, from three public urban schools were included. Anthropometric, blood pressure, and dietary assessment (two multiple pass 24-hour recalls) were done. More than half of children did not meet the fruit and vegetable recommended intake. High-fat dairy foods (14% of total energy intake), refined carbohydrates (13.5%), red/processed meat (8.5%), added sugars/desserts (7%), corn tortilla (6.5%), and soft drinks/sweetened beverages (5%) were the highest dietary energy sources consumed. In a subgroup of children (n=185), a fasting blood sample was collected for biochemical analysis. A positive association was observed between glucose and diastolic blood pressure with the intake of soft drinks/sweetened beverages, insulin concentrations and the intake of white bread, and triglyceride concentrations with the intake of added fats. Unhealthful dietary energy sources are frequently consumed by these children. Culturally competent nutrition counseling should be offered to Mexican-American children and their families with a significant risk of cardiovascular disease. Efforts should be made to design and implement nutrition education and health promotion strategies in schools.

  7. Markers of Oxidative and Nitrosative Stress in Systemic Lupus Erythematosus: Correlation with Disease Activity

    PubMed Central

    Wang, Gangduo; Pierangeli, Silvia S.; Papalardo, Elizabeth; Ansari, G.A.S.; Khan, M. Firoze

    2010-01-01

    Objective Free radical-mediated reactions have been implicated as contributors in a number of autoimmune disease (ADs) including SLE. However, potential of oxidative/nitrosative stress in eliciting an autoimmune response, or in disease prognosis and pathogenesis in humans remains largely unexplored. This study investigates the status and contribution of oxidative/nitrosative stress in SLE. Methods Sera from 72 SLE patients with various SLE scores [SLE disease activity index (SLEDAI)] and 36 age- and gender-matched controls were evaluated for oxidative/nitrosative stress markers, such as anti-malondialdehyde (MDA)- and anti-4-hydroxynonenal (HNE)-protein adduct antibodies, MDA-/HNE-protein adducts, superoxide dismutase (SOD), nitrotyrosine and iNOS. Results Serum analysis showed significantly higher levels of both anti-MDA-/anti-HNE-protein adduct antibodies and MDA-/HNE-protein adducts in SLE patients. Interestingly, our data showed not only increased number of subjects positive for anti-MDA- or anti-HNE-protein antibodies, but also greater increases in both these antibodies in SLE patients with greater SLEDAI (≥ 6), which were significantly higher than the lower SLEDAI group (<6). Data also showed a significant correlation between anti-MDA or anti-HNE antibodies and SLEDAI (r = 0.734 and 0.647 for anti-MDA and anti-HNE antibodies, respectively) suggesting a possible causal relationship between these antibodies and SLE. Furthermore, sera from SLE patients had lower levels of SOD, and higher levels of iNOS and nitrotyrosine. Conclusion Our findings support an association between oxidative/nitrosative stress and SLE. Stronger response in samples with higher SLEDAI suggests that oxidative/nitrosative stress markers may be useful in evaluating the progression of SLE as well as in elucidating the mechanisms of disease pathogenesis. PMID:20201076

  8. Precise assembly and regulation of 26S proteasome and correlation between proteasome dysfunction and neurodegenerative diseases

    PubMed Central

    Im, Eunju; Chung, Kwang Chul

    2016-01-01

    Neurodegenerative diseases (NDs) often involve the formation of abnormal and toxic protein aggregates, which are thought to be the primary factor in ND occurrence and progression. Aged neurons exhibit marked increases in aggregated protein levels, which can lead to increased cell death in specific brain regions. As no specific drugs/therapies for treating the symptoms or/and progression of NDs are available, obtaining a complete understanding of the mechanism underlying the formation of protein aggregates is needed for designing a novel and efficient removal strategy. Intracellular proteolysis generally involves either the lysosomal or ubiquitin-proteasome system. In this review, we focus on the structure and assembly of the proteasome, proteasome-mediated protein degradation, and the multiple dynamic regulatory mechanisms governing proteasome activity. We also discuss the plausibility of the correlation between changes in proteasome activity and the occurrence of NDs. [BMB Reports 2016; 49(9): 459-473] PMID:27312603

  9. Precise assembly and regulation of 26S proteasome and correlation between proteasome dysfunction and neurodegenerative diseases.

    PubMed

    Im, Eunju; Chung, Kwang Chul

    2016-09-01

    Neurodegenerative diseases (NDs) often involve the formation of abnormal and toxic protein aggregates, which are thought to be the primary factor in ND occurrence and progression. Aged neurons exhibit marked increases in aggregated protein levels, which can lead to increased cell death in specific brain regions. As no specific drugs/therapies for treating the symptoms or/and progression of NDs are available, obtaining a complete understanding of the mechanism underlying the formation of protein aggregates is needed for designing a novel and efficient removal strategy. Intracellular proteolysis generally involves either the lysosomal or ubiquitin-proteasome system. In this review, we focus on the structure and assembly of the proteasome, proteasome-mediated protein degradation, and the multiple dynamic regulatory mechanisms governing proteasome activity. We also discuss the plausibility of the correlation between changes in proteasome activity and the occurrence of NDs. [BMB Reports 2016; 49(9): 459-473].

  10. Impaired finger dexterity in patients with parkinson's disease correlates with discriminative cutaneous sensory dysfunction.

    PubMed

    Lee, Myung Sik; Lyoo, Chul Hyoung; Lee, Myung Jun; Sim, Jaeeun; Cho, Hanna; Choi, Yun Ho

    2010-11-15

    To study the influence of discriminative cutaneous sensory dysfunction on impaired finger dexterity in Parkinson's disease (PD), we evaluated 48 right-handed PD patients during a practically defined off-medication period and 24 healthy age-matched controls. With visual deprivation, a finger tapping task (FTT) was performed to assess the speed of simple repetitive finger movements and a coin rotation task (CRT) was used to assess finger dexterity. The tasks were performed with the right hand. We measured the somesthetic temporal discrimination threshold (sTDT) in the right index finger. The mean ± SD FTT score of the patient group was lower than that of the control group (24.0 ± 8.0 vs. 29.8 ± 7.8; P < 0.01). The patient group performed worse on the CRT than the control group (8.5 ± 3.5 vs. 12.6 ± 1.7; P < 0.001). The mean sTDT value of the patient group was longer than that of the control group (124.0 ± 44.8 vs. 78.1 ± 26.2 ms; P < 0.001). The CRT scores correlated with the sTDT values (Pearson's correlation coefficient = -0.43; P < 0.01), but not with the Unified Parkinson's Disease Rating Scale (UPDRS) finger bradykinesia scores or FTT scores. Multiple regression analysis showed that the sTDT values (parameter estimate = -0.03, SE = 0.01; P < 0.01), but not patient age, UPDRS finger bradykinesia score, or FTT score, affected the CRT score. Slowness of simple repetitive finger movements did not have a strong impact on the impaired manual dexterity of PD. Discriminative sensory dysfunction and consequent abnormal sensorimotor integration seem to be involved in the impaired finger dexterity of PD.

  11. Anatomical Substrate and Scalp EEG Markers are Correlated in Subjects with Cognitive Impairment and Alzheimer's Disease.

    PubMed

    Moretti, Davide V; Frisoni, Giovanni B; Binetti, Giuliano; Zanetti, Orazio

    2011-01-01

    Dementia is a syndromic diagnosis, encompassing various stage of severity and different anatomo-physiological substrates. The hippocampus is one of the first and most affected brain regions affected by both Alzheimer's disease (AD) and mild cognitive impairment (MCI). Moreover, chronic cerebrovascular disease (CVD) is one of the major risk factor for developing dementia. Recent studies have demonstrated different relationship between the anatomical substrate and scalp electroencephalography (EEG) markers. Indeed, modifications of EEG rhythmicity is not proportional to the hippocampal atrophy, whereas changes in EEG activity are directly proportional to the load of subcortical CVD. The computation of the EEG spectral power and the analysis of the functional coupling of brain areas, through linear coherence, are two of the most known processing methods in EEG research. Two specific EEG markers, theta/gamma and alpha3/alpha2 frequency ratio have been reliable associated to the atrophy of amygdalo-hippocampal complex. Moreover, theta/gamma ratio has been related to MCI conversion in dementia and alpha3/alpha2 ratio has been specifically related to MCI conversion in AD. The functional coupling of brain areas is also modulated by hippocampal atrophy. In the MCI subjects, hippocampal atrophy is linked to an increase of interhemispheric coherence seen on frontal and temporal regions whereas subcortical CVD is linked to a decrease of coherence in fronto-parietal regions. In the present study the most significant results of recent studies on correlation between scalp EEG, cognitive decline, and anatomical substrate have been reviewed, with particular attention to the relationships between EEG changes and hippocampal atrophy. The following review is not intended to provide a comprehensive summary of the literature. Rather it identifies and discusses selected studies that are designed to find the specific correlation between scalp EEG markers and anatomo-pathological substrate

  12. Subthalamic nucleus phase–amplitude coupling correlates with motor impairment in Parkinson’s disease

    PubMed Central

    van Wijk, Bernadette C.M.; Beudel, Martijn; Jha, Ashwani; Oswal, Ashwini; Foltynie, Tom; Hariz, Marwan I.; Limousin, Patricia; Zrinzo, Ludvic; Aziz, Tipu Z.; Green, Alexander L.; Brown, Peter; Litvak, Vladimir

    2016-01-01

    Objective High-amplitude beta band oscillations within the subthalamic nucleus are frequently associated with Parkinson’s disease but it is unclear how they might lead to motor impairments. Here we investigate a likely pathological coupling between the phase of beta band oscillations and the amplitude of high-frequency oscillations around 300 Hz. Methods We analysed an extensive data set comprising resting-state recordings obtained from deep brain stimulation electrodes in 33 patients before and/or after taking dopaminergic medication. We correlated mean values of spectral power and phase–amplitude coupling with severity of hemibody bradykinesia/rigidity. In addition, we used simultaneously recorded magnetoencephalography to look at functional interactions between the subthalamic nucleus and ipsilateral motor cortex. Results Beta band power and phase–amplitude coupling within the subthalamic nucleus correlated positively with severity of motor impairment. This effect was more pronounced within the low-beta range, whilst coherence between subthalamic nucleus and motor cortex was dominant in the high-beta range. Conclusions We speculate that the beta band might impede pro-kinetic high-frequency activity patterns when phase–amplitude coupling is prominent. Furthermore, results provide evidence for a functional subdivision of the beta band into low and high frequencies. Significance Our findings contribute to the interpretation of oscillatory activity within the cortico-basal ganglia circuit. PMID:26971483

  13. Correlation of MRI Visual Scales with Neuropsychological Profile in Mild Cognitive Impairment of Parkinson's Disease

    PubMed Central

    Pereira, João Santos; Adachi, Marcelo; Greca, Denise; Cruz, Manuela; Malak, Ana Lara; Charchat-Fichman, Helenice; Spitz, Mariana

    2017-01-01

    Few studies have evaluated magnetic resonance imaging (MRI) visual scales in Parkinson's disease-Mild Cognitive Impairment (PD-MCI). We selected 79 PD patients and 92 controls (CO) to perform neurologic and neuropsychological evaluation. Brain MRI was performed to evaluate the following scales: Global Cortical Atrophy (GCA), Fazekas, and medial temporal atrophy (MTA). The analysis revealed that both PD groups (amnestic and nonamnestic) showed worse performance on several tests when compared to CO. Memory, executive function, and attention impairment were more severe in amnestic PD-MCI group. Overall analysis of frequency of MRI visual scales by MCI subtype did not reveal any statistically significant result. Statistically significant inverse correlation was observed between GCA scale and Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), semantic verbal fluency, Stroop test, figure memory test, trail making test (TMT) B, and Rey Auditory Verbal Learning Test (RAVLT). The MTA scale correlated with Stroop test and Fazekas scale with figure memory test, digit span, and Stroop test according to the subgroup evaluated. Visual scales by MRI in MCI should be evaluated by cognitive domain and might be more useful in more severely impaired MCI or dementia patients.

  14. Correlation of MRI Visual Scales with Neuropsychological Profile in Mild Cognitive Impairment of Parkinson's Disease.

    PubMed

    Vasconcellos, Luiz Felipe; Pereira, João Santos; Adachi, Marcelo; Greca, Denise; Cruz, Manuela; Malak, Ana Lara; Charchat-Fichman, Helenice; Spitz, Mariana

    2017-01-01

    Few studies have evaluated magnetic resonance imaging (MRI) visual scales in Parkinson's disease-Mild Cognitive Impairment (PD-MCI). We selected 79 PD patients and 92 controls (CO) to perform neurologic and neuropsychological evaluation. Brain MRI was performed to evaluate the following scales: Global Cortical Atrophy (GCA), Fazekas, and medial temporal atrophy (MTA). The analysis revealed that both PD groups (amnestic and nonamnestic) showed worse performance on several tests when compared to CO. Memory, executive function, and attention impairment were more severe in amnestic PD-MCI group. Overall analysis of frequency of MRI visual scales by MCI subtype did not reveal any statistically significant result. Statistically significant inverse correlation was observed between GCA scale and Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), semantic verbal fluency, Stroop test, figure memory test, trail making test (TMT) B, and Rey Auditory Verbal Learning Test (RAVLT). The MTA scale correlated with Stroop test and Fazekas scale with figure memory test, digit span, and Stroop test according to the subgroup evaluated. Visual scales by MRI in MCI should be evaluated by cognitive domain and might be more useful in more severely impaired MCI or dementia patients.

  15. Neuropsychological correlates of theory of mind in patients with early Parkinson's disease.

    PubMed

    Santangelo, Gabriella; Vitale, Carmine; Trojano, Luigi; Errico, Domenico; Amboni, Marianna; Barbarulo, Anna Maria; Grossi, Dario; Barone, Paolo

    2012-01-01

    The theory of mind is the ability to attribute mental states to oneself and others and to understand that others have beliefs, desires and intentions different from one's own. The aim of the study was to explore the neuropsychological correlates of theory of mind in patients affected by early Parkinson's disease (PD). Thirty-three PD patients and 33 age-, sex-, and education-matched control subjects underwent the Frontal Assessment Battery, as well as tasks assessing "cognitive" and "affective" theory of mind, and memory abilities; questionnaires evaluating behavioral disorders and quality of life were also administrated. Although the 2 groups did not differ on neuropsychological tasks, PD patients' performance on tasks assessing cognitive and affective theory of mind was significantly worse than controls. Moreover, PD patients had more behavioral disorders and worse quality of life than controls. After covarying for behavioral and quality of life scores, the differences between patients and controls on theory of mind tasks remained significant. "Cognitive" theory of mind was associated with Frontal Assessment Battery score and 2 domains of quality of life scale, whereas "affective" theory of mind scores correlated only with behavioral scales such as the Frontal Behavioral Inventory and Apathy Evaluation Scale. The results demonstrate that both affective and cognitive aspects of theory of mind are simultaneously impaired in early PD and suggest that deficits in the 2 subcomponents of theory of mind may be linked to dysfunction of different frontosubcortical circuitries in early PD.

  16. Structural and functional brain network correlates of depressive symptoms in premanifest Huntington's disease.

    PubMed

    McColgan, Peter; Razi, Adeel; Gregory, Sarah; Seunarine, Kiran K; Durr, Alexandra; A C Roos, Raymund; Leavitt, Blair R; Scahill, Rachael I; Clark, Chris A; Langbehn, Doug R; Rees, Geraint; Tabrizi, Sarah J

    2017-03-15

    Depression is common in premanifest Huntington's disease (preHD) and results in significant morbidity. We sought to examine how variations in structural and functional brain networks relate to depressive symptoms in premanifest HD and healthy controls. Brain networks were constructed using diffusion tractography (70 preHD and 81 controls) and resting state fMRI (92 preHD and 94 controls) data. A sub-network associated with depression was identified in a data-driven fashion and network-based statistics was used to investigate which specific connections correlated with depression scores. A replication analysis was then performed using data from a separate study. Correlations between depressive symptoms with increased functional connectivity and decreased structural connectivity were seen for connections in the default mode network (DMN) and basal ganglia in preHD. This study reveals specific connections in the DMN and basal ganglia that are associated with depressive symptoms in preHD. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  17. Seroprevalence of Bartonella henselae infection and correlation with disease status in cats in Switzerland.

    PubMed

    Glaus, T; Hofmann-Lehmann, R; Greene, C; Glaus, B; Wolfensberger, C; Lutz, H

    1997-11-01

    The prevalence of infection with Bartonella henselae was investigated in cats from different areas of Switzerland. Serum samples of 728 cats were examined for antibodies to B. henselae by immunofluorescent antibody testing, and the results were analyzed with a view to a possible correlation between a positive titer and signalment, clinical signs, infection with feline leukemia virus (FeLV), feline immunodeficiency virus (FIV), feline coronavirus (FCoV), or feline spumavirus (FeSFV), and the living environments of the cats. The seroprevalence in all cats was 8.3%. No significantly different prevalence was found in sick versus healthy cats (9.2 versus 7.2%); however, in sick cats seropositive for B. henselae, there was an increased frequency of stomatitis and a variety of diseases of the kidneys and the urinary tract. There was an increased prevalence of B. henselae in cats positive for FCoV (P = 0.0185) or FeSFV (P = 0.0235) and no statistically significant increased prevalence in cats infected with FeLV or FIV. There was no correlation between a positive titer and sex or breed. The same prevalence of B. henselae antibodies was found in cats with and without access to the outdoors and in cats from single- and multicat households. The seroprevalence was increased in cats living south of the Alps (12.1%); however, this difference was not significant (P = 0.0616).

  18. Brain perfusion correlates of visuoperceptual deficits in Mild Cognitive Impairment and mild Alzheimer’s disease

    PubMed Central

    Alegret, Montserrat; Vinyes-Junqué, Georgina; Boada, Mercè; Martínez-Lage, Pablo; Cuberas, Gemma; Espinosa, Ana; Roca, Isabel; Hernández, Isabel; Valero, Sergi; Rosende-Roca, Maitée; Mauleón, Ana; Becker, James T.; Tárraga, Lluís

    2012-01-01

    Background Visuoperceptual processing is impaired early in the clinical course of Alzheimer’s disease (AD). The 15-Objects Test (15-OT) detects such subtle performance deficits in Mild Cognitive Impairment (MCI) and mild AD. Reduced brain perfusion in the temporal, parietal and prefrontal regions have been found in early AD and MCI patients. Objectives To confirm the role of the 15-OT in the diagnosis of MCI and AD, and to investigate the brain perfusion correlates of visuoperceptual dysfunction (15-OT) in subjects with MCI, AD and normal aging. Methods Forty-two AD, 42 MCI and 42 healthy elderly control (EC) subjects underwent a brain Single Photon Emission Tomography (SPECT) and separately completed the 15-OT. An analysis of variance compared 15-OT scores between groups. SPM5 was used to analyse the SPECT data. Results 15-OT performace was impaired in the MCI and AD patients. In terms of the SPECT scans, AD patients showed reduced perfusion in temporal-parietal regions, while the MCI subjects had decreased perfusion in the middle and posterior cingulate. When MCI and AD groups were compared, a significant brain perfusion reduction was found in temporo-parietal regions. In the whole sample, 15-OT performance was significantly correlated with the clinical dementia rating scores, and with the perfusion in the bilateral posterior cingulate and the right temporal pole, with no significant correlation in each separate group. Conclusion Our findings suggest that the 15-OT performance provides a useful gradation of impairment from normal aging to AD, and it seems to be related to perfusion in the bilateral posterior cingulate and the right temporal pole. PMID:20555146

  19. Breath condensate nitrite correlates with hyperinflation in chronic obstructive pulmonary disease.

    PubMed

    Gessner, Christian; Hammerschmidt, Stefan; Kuhn, Hartmut; Hoheisel, Gerhard; Gillissen, Adrian; Sack, Ulrich; Wirtz, Hubert

    2007-11-01

    Estimating the degree of pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) is not always straight forward. Standard pulmonary function tests provide only a crude estimate of this important aspect of COPD. In addition, good patient cooperation cannot always be achieved and therefore adds to the uncertainties with regard to the extent of hyperinflation of the lung. The aim of this investigation was to characterize exhaled breath condensate nitrite in volunteers, healthy smokers, and stable COPD (GOLD-stages 0-4) and to compare this parameter with inflammatory markers in exhaled breath condensate and with lung function in order to test the hypothesis that elevated exhaled breath condensate nitrite reflects hyperinflation in COPD. We found a logarithmic correlation of exhaled breath condensate nitrite to residual volume (r=0.75, p<0.0001), total lung capacity (r=0.51, p<0.0001), and thoracic gas volume (r=0.71, p<0.0001) but no correlation of exhaled breath condensate nitrite concentrations with levels of inflammatory cytokines in exhaled breath condensate (interleukin (IL)-8, IL-1beta, IL-6, IL-10, IL-12, and tumor necrosis factor-alpha). Analysis of COPD subgroups revealed a logarithmic correlation of EBC nitrite to residual volume, total lung capacity, and intrathoracic gas volume exclusively for patients characterized by GOLD classes 2, and higher. Our results confirm a relation of exhaled breath condensate nitrite levels and hyperinflation measured by conventional pulmonary function tests. Investigations using isolated lung models and cells stretched in culture also provide insight into this relation. Exhaled breath condensate nitrite may be a biochemical indicator of pulmonary overdistension.

  20. Clinical Correlates of Apathy in Patients Recently Diagnosed with Parkinson's Disease: The ANIMO Study

    PubMed Central

    Cubo, Esther; Benito-León, Julián; Coronell, Carlos; Armesto, Diana

    2012-01-01

    Objective Little is known about apathy in the early stages of Parkinson's disease (PD). We determined the clinical correlates of apathy in a large representative sample of patients recently diagnosed with PD (ANIMO study). Methods PD patients, diagnosed within 2 years of inclusion, were recruited in 102 outpatient clinics situated in 82 populations throughout Spain. Apathy was quantified using the Lille Apathy Rating Scale (LARS). Clinical comparisons and correlations were performed using nonparametric tests. Regression analyses were used to test the association of clinical variables with apathy. Results We recruited 557 PD patients (60.3% men) with a mean age of 68.8 ± 9.7 years, and UPDRS motor score of 21.1 ± 10.8. Apathy only was diagnosed in 186 (33.4%), and apathy and depression in 215 patients (38.6%). Patients with higher comorbidity (OR = 1.10, 95% CI 1.01−1.20, p = 0.001), motor impairment (OR = 1.07, 95% CI 1.03−1.10, p < 0.0001), and lower education (OR = 2.16, 95% CI 1.21−;3.85, p = 0.009) had higher odds of having apathy, in contrast to patients living in a rural environment (OR = 0.35, 95% CI 0.32–0.85, p = 0.01), and left predominant PD motor laterality (OR = 0.34, 95% CI 0.13–0.88, p = 0.01). LARS scores were significantly correlated with UPDRS motor scores (rs = 0.44, p < 0.001), predominantly with axial score (rs = 0.43, p < 0.001). Conclusions In PD, apathy is a very common and disabling nonmotor symptom separable from depression. Patients living in a rural environment, with lower comorbidity and motor impairment, higher education background, and left predominant PD motor laterality are at lower risk of suffering from apathy. PMID:22236943

  1. Buccal Cell Cytokeratin 14 Correlates with Multiple Blood Biomarkers of Alzheimer's Disease Risk.

    PubMed

    Leifert, Wayne R; Nguyen, Tori; Rembach, Alan; Martins, Ralph; Rainey-Smith, Stephanie; Masters, Colin L; Ames, David; Rowe, Christopher C; Macaulay, S Lance; François, Maxime; Fenech, Michael F

    2015-01-01

    Mild cognitive impairment (MCI) may reflect early stages of neurodegenerative disorders such as Alzheimer's disease (AD). Our hypothesis was that cytokeratin 14 (CK14) expression could be used with blood-based biomarkers such as homocysteine, vitamin B12, and folate to identify individuals with MCI or AD from the Australian Imaging, Biomarkers and Lifestyle (AIBL) flagship study of aging. Buccal cells from 54 individuals were analyzed by a newly developed method that is rapid, automated, and quantitative for buccal cell CK14 expression levels. CK14 was negatively correlated with plasma Mg²⁺ and LDL, while positively correlated with vitamin B12, red cell hematocrit/volume, and basophils in the MCI group and positively correlated with insulin and vitamin B12 in the AD group. The combined biomarker panel (CK14 expression, plasma vitamin B12, and homocysteine) was significantly lower in the MCI (p = 0.003) and AD (p = 0.0001) groups compared with controls. Receiver-operating characteristic curves yielded area under the curve (AUC) values of 0.829 for the MCI (p = 0.002) group and 0.856 for the AD (p = 0.0003) group. These complex associations of multiple related parameters highlight the differences between the MCI and AD cohorts and possibly an underlying metabolic pathology associated with the development of early memory impairment. The changes in buccal cell CK14 expression observed in this pilot study supports previous results suggesting the peripheral biomarkers and metabolic changes are not restricted to brain pathology alone in MCI and AD and could prove useful as a potential biomarker in identifying individuals with an increased risk of developing MCI and eventually AD.

  2. Severity of atopic disease inversely correlates with intestinal microbiota diversity and butyrate-producing bacteria.

    PubMed

    Nylund, L; Nermes, M; Isolauri, E; Salminen, S; de Vos, W M; Satokari, R

    2015-02-01

    The reports on atopic diseases and microbiota in early childhood remain contradictory, and both decreased and increased microbiota diversity have been associated with atopic eczema. In this study, the intestinal microbiota signatures associated with the severity of eczema in 6-month-old infants were characterized. Further, the changes in intestinal microbiota composition related to the improvement of this disease 3 months later were assessed. The severity of eczema correlated inversely with microbiota diversity (r = -0.54, P = 0.002) and with the abundance of butyrate-producing bacteria (r = -0.52, P = 0.005). During the 3-month follow-up, microbiota diversity increased (P < 0.001) and scoring atopic dermatitis values decreased (P < 0.001) in all infants. This decrease coincided with the increase in bacteria related to butyrate-producing Coprococcus eutactus (r = -0.59, P = 0.02). In conclusion, the high diversity of microbiota and high abundance of butyrate-producing bacteria were associated with milder eczema, thus suggesting they have a role in alleviating symptoms of atopic eczema.

  3. Finding Leading Indicators for Disease Outbreaks: Filtering, Cross-correlation, and Caveats

    PubMed Central

    Bloom, Ronald M.; Buckeridge, David L.; Cheng, Karen E.

    2007-01-01

    Bioterrorism and emerging infectious diseases such as influenza have spurred research into rapid outbreak detection. One primary thrust of this research has been to identify data sources that provide early indication of a disease outbreak by being leading indicators relative to other established data sources. Researchers tend to rely on the sample cross-correlation function (CCF) to quantify the association between two data sources. There has been, however, little consideration by medical informatics researchers of the influence of methodological choices on the ability of the CCF to identify a lead–lag relationship between time series. We draw on experience from the econometric and environmental health communities, and we use simulation to demonstrate that the sample CCF is highly prone to bias. Specifically, long-scale phenomena tend to overwhelm the CCF, obscuring phenomena at shorter wave lengths. Researchers seeking lead–lag relationships in surveillance data must therefore stipulate the scale length of the features of interest (e.g., short-scale spikes versus long-scale seasonal fluctuations) and then filter the data appropriately—to diminish the influence of other features, which may mask the features of interest. Otherwise, conclusions drawn from the sample CCF of bi-variate time-series data will inevitably be ambiguous and often altogether misleading. PMID:17068353

  4. Fractal correlation property of heart rate variability in chronic obstructive pulmonary disease

    PubMed Central

    Carvalho, Tatiana D; Pastre, Carlos Marcelo; de Godoy, Moacir Fernandes; Fereira, Celso; Pitta, Fábio O; de Abreu, Luiz Carlos; Ramos, Ercy Mara Cipulo; Valenti, Vitor E; Vanderlei, Luiz Carlos Marques

    2011-01-01

    Background It was reported that autonomic nervous system function is altered in subjects with chronic obstructive pulmonary disease (COPD). We evaluated short- and long-term fractal exponents of heart rate variability (HRV) in COPD subjects. Patients and methods We analyzed data from 30 volunteers, who were divided into two groups according to spirometric values: COPD (n = 15) and control (n = 15). For analysis of HRV indices, HRV was recorded beat by beat with the volunteers in the supine position for 30 minutes. We analyzed the linear indices in the time (SDNN [standard deviation of normal to normal] and RMSSD [root-mean square of differences]) and frequency domains (low frequency [LF], high frequency [HF], and LF/HF), and the short- and long-term fractal exponents were obtained by detrended fluctuation analysis. We considered P < 0.05 to be a significant difference. Results COPD patients presented reduced levels of all linear exponents and decreased short-term fractal exponent (alpha-1: 0.899 ± 0.18 versus 1.025 ± 0.09, P = 0.026). There was no significant difference between COPD and control groups in alpha-2 and alpha-1/alpha-2 ratio. Conclusion COPD subjects present reduced short-term fractal correlation properties of HRV, which indicates that this index can be used for risk stratification, assessment of systemic disease manifestations, and therapeutic procedures to monitor those patients. PMID:21311690

  5. Gene regulations in HBV-related liver cirrhosis closely correlate with disease severity.

    PubMed

    Lee, Seram; Kim, Soyoun

    2007-09-30

    Liver cirrhosis (LC) is defined as comprising diffuse fibrosis and regenerating nodules of the liver. The biochemical and anatomical dysfunction in LC results from both reduced liver cell number and portal vascular derangement. Although several studies have investigated dysregulated genes in cirrhotic nodules, little is known about the genes implicated in the pathophysiologic change of LC or about their relationship with the degree of decompensation. Here, we applied cDNA microarray analysis using 38 HBsAg-positive LC specimens to identify the genes dysregulated in HBV-associated LC and to evaluate their relation to disease severity. Among 1063 known cancer- and apoptosis-related genes, we identified 104 genes that were significantly up- (44) or down- (60) regulated in LC. Interestingly, this subset of 104 genes was characteristically correlated with the degree of decompensation, called the Pugh-Child classification (20 Pugh-Child A, 10 Pugh-Child B, and 8 Pugh-Child C). Patient samples from Pugh-Child C exhibited a distinct pattern of gene expression relative to those of Pugh-Child A and B. Especially in Pugh-Child C, genes encoding hepatic proteins and metabolizing enzymes were significantly down-regulated, while genes encoding various molecules related to cell replication were up-regulated. Our results suggest that subsets of genes in liver cells correspond to the pathophysiologic change of LC according to disease severity and possibly to hepatocarcinogenesis.

  6. Pathological and Clinical Correlation between Celiac Disease and Helicobacter Pylori Infection; a Review of Controversial Reports

    PubMed Central

    Rostami-Nejad, Mohammad; Javad Ehsani-Ardakani, Mohammad; Assadzadeh, Hamid; Shahbazkhani, Bijan; Ierardi, Enzo; Losurdo, Giuseppe; Zojaji, Homayon; Alizadeh, Amirhoshang Mohammad; Naderi, Nosratollah; Sadeghi, Amir; Zali, Mohammad Reza

    2016-01-01

    There are overwhelming reports and descriptions about celiac associated disorders. Although there is a clear genetic association between celiac disease (CD) and some gastrointestinal disorders, there are controversial reports claiming an association between CD and Helicobacter pylori (H. pylori) infection. Different studies indicated the possible association between lymphocytic gastritis and both CD and H. pylori infection, although this evidence is not consistently accepted. Also it was shown that an increase in intraepithelial lymphocytes count is associated with both H. pylori infection and celiac disease. Therefore the following questions may raise: how far is this infection actually related to CD?, which are the underlying patho-mechanisms for these associations? what are the clinical implications? what is the management? and what would be the role of gluten free diet in treating these conditions? PubMed (PubMed Central), Ovid, ISI of web knowledge, and Google scholar were searched for full text articles published between 1985 and 2015. The associated keywords were used, and papers described particularly the impact of pathological and clinical correlation between CD and H. pylori infection were identified. In this review we tried to answer the above questions and discussed some of the recent developments in the pathological and clinical aspects of CD and H. pylori infection. PMID:27252814

  7. Pathological and Clinical Correlation between Celiac Disease and Helicobacter Pylori Infection; a Review of Controversial Reports.

    PubMed

    Rostami-Nejad, Mohammad; Javad Ehsani-Ardakani, Mohammad; Assadzadeh, Hamid; Shahbazkhani, Bijan; Ierardi, Enzo; Losurdo, Giuseppe; Zojaji, Homayon; Alizadeh, Amirhoshang Mohammad; Naderi, Nosratollah; Sadeghi, Amir; Zali, Mohammad Reza

    2016-04-01

    There are overwhelming reports and descriptions about celiac associated disorders. Although there is a clear genetic association between celiac disease (CD) and some gastrointestinal disorders, there are controversial reports claiming an association between CD and Helicobacter pylori (H. pylori) infection. Different studies indicated the possible association between lymphocytic gastritis and both CD and H. pylori infection, although this evidence is not consistently accepted. Also it was shown that an increase in intraepithelial lymphocytes count is associated with both H. pylori infection and celiac disease. Therefore the following questions may raise: how far is this infection actually related to CD?, which are the underlying patho-mechanisms for these associations? what are the clinical implications? what is the management? and what would be the role of gluten free diet in treating these conditions? PubMed (PubMed Central), Ovid, ISI of web knowledge, and Google scholar were searched for full text articles published between 1985 and 2015. The associated keywords were used, and papers described particularly the impact of pathological and clinical correlation between CD and H. pylori infection were identified. In this review we tried to answer the above questions and discussed some of the recent developments in the pathological and clinical aspects of CD and H. pylori infection.

  8. Neuropsychological Correlates of Capacity Determinations in Alzheimer’s Disease: Implications for Assessment

    PubMed Central

    Palmer, Barton W.; Ryan, Kerry A.; Kim, H. Myra; Karlawish, Jason H.; Appelbaum, Paul S.; Kim, Scott Y. H.

    2011-01-01

    Objectives To explore the neuropsychological correlates of the capacity to consent to research and to appoint a research proxy among persons with Alzheimer’s disease. Design, Setting, and Participants Interview study of 77 persons with Alzheimer’s disease recruited through an Alzheimer’s disease research center and a memory disorder clinic. Measurements The capacity to consent to two research scenarios (a drug randomized clinical trial and a neurosurgical clinical trial) and the capacity to appoint a research proxy were determined by five experienced consultation psychiatrists who rendered categorical judgments based on videotaped interviews of the MacArthur Competence Assessment Tool-Clinical Research (MacCAT-CR) and the Capacity to Appoint a Proxy Assessment (CAPA). Mattis Dementia Rating Scale-2 (DRS-2) was used to assess neuropsychological functioning. Results The capacity to appoint a proxy and to consent to the drug randomized clinical trial, as determined by a majority or greater opinion of the 5-psychiatrist panel, were predicted by Conceptualization and Initiation/Perseveration subscales whereas the capacity to consent to a neurosurgical randomized clinical trial was predicted by the Memory subscale. Furthermore, the more lenient individual psychiatrists’ judgments were predicted by the Conceptualization subscale whereas the stricter psychiatrists’ judgments were predicted by the Memory subscale. Conclusions How experienced psychiatrists view Alzheimer’s patients’ capacity for consenting to research and for appointing a proxy may be related to the patients’ conceptualization and memory functioning. More explicit and standardized guidance on the role of short term memory in capacity determinations may be useful. PMID:23498384

  9. Experiential and Doctrinal Religious Knowledge Categorization in Parkinson's Disease: Behavioral and Brain Correlates

    PubMed Central

    Modestino, Edward J.; O'Toole, Partrick; Reinhofer, AnnaMarie

    2016-01-01

    Recent studies suggest changes in religious cognition in a subgroup of patients with Parkinson's disease (PD e.g., Butler et al., 2011). It is unclear whether this deficit extends to both doctrinal and experiential categorization forms of religious cognition. Kapogiannis et al. (2009b) dissociated experiential and doctrinal religious knowledge to different neural networks using fMRI. We examined Kapogiannis' dissociation against the background of PD side of onset (LOPD, ROPD), assessing performance both On- and Off-medication. In the behavioral portion of the study, we used a statement classification task in combination with scholar derived test sets for experiential and doctrinal religious knowledge categorization in conjunction with neuropsychological measures. In the neuroimaging portion of the study, we expanded on Kapogiannis' study by examining the same networks in PD. The behavioral data revealed that all groups rated (categorized) the scholar derived tests of experiential and doctrinal significantly differently than the scholars. All groups, including the scholars, classified more phrases as doctrinal than experiential. Religious cognition differed in the PD groups: those with PD Off-medication and LOPD Off-medication comprehended scholar defined experiential phrases with more difficulty, making them more likely to be classified as mixed or doctrinal. This was in contrast to the subjective frequency of classification of phrases as experiential paired with a cognitive decline in PD Off-medication; whereas PD On-medication showed a positive correlation with cognitive state and subjective doctrinal classification. For ROPD, cognitive state was associated with subjective experiential and doctrinal frequency of classification. With more intact intellect, there was a greater likelihood of classifying phrases subjectively as mixed, and the converse for experiential. Furthermore, religiosity negatively predicted subjective doctrinal frequency in LOPD, with the

  10. Correlation of low levels of nitrite and high levels of fetal hemoglobin in patients with sickle cell disease at baseline

    PubMed Central

    Elias, Darcielle Bruna Dias; Rocha, Lilianne Brito da Silva; Cavalcante, Maritza Barbosa; Pedrosa, Alano Martins; Justino, Izabel Cristina Bandeira; Gonçalves, Romélia Pinheiro

    2012-01-01

    Background Sickle cell disease is a hemoglobinopathy characterized by hemolytic anemia, increased susceptibility to infections and recurrent vaso-occlusive crises that reduces the quality of life of sufferers. Objective To evaluate the correlation of the levels of lactate dehydrogenase, malonaldehyde and nitrite to fetal hemoglobin in patients with sickle cell disease not under treatment with hydroxyurea in outpatients at a university hospital in Fortaleza, Ceará, Brazil. Methods Forty-four patients diagnosed with sickle cell disease were enrolled at baseline. Diagnosis was confirmed by evaluating the beta globin gene using polymerase chain reaction-restriction fragment length polymorphism. The concentration of fetal hemoglobin was obtained by high-performance liquid chromatography. Serum levels of nitrite, malonaldehyde and lactate dehydrogenase were measured by biochemical methods. Results Significantly higher levels of lactate dehydrogenase, nitrite and malonaldehyde were observed in patients with sickle cell disease compared to a control group. The study of the correlation between fetal hemoglobin levels and these variables showed a negative correlation with nitrite levels. No correlation was found between fetal hemoglobin and malonaldehyde or lactate dehydrogenase. When the study population was stratified according to fetal hemoglobin levels, a decrease in the levels of nitrite was observed with higher levels of fetal hemoglobin (p-value = 0.0415). Conclusion The results show that, similar to fetal hemoglobin levels, the concentration of nitrite can predict the clinical course of the disease, but should not be used alone as a modulator of prognosis in patients with sickle cell disease. PMID:23049438

  11. Toxoplasmosis – A Global Threat. Correlation of Latent Toxoplasmosis with Specific Disease Burden in a Set of 88 Countries

    PubMed Central

    Flegr, Jaroslav; Prandota, Joseph; Sovičková, Michaela; Israili, Zafar H.

    2014-01-01

    Background Toxoplasmosis is becoming a global health hazard as it infects 30–50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this ‘asymptomatic infection’ may also lead to development of other human pathologies. Aims of the Study The purpose of the study was to collect available geoepidemiological data on seroprevalence of toxoplasmosis and search for its relationship with mortality and disability rates in different countries. Methods and Findings Prevalence data published between 1995–2008 for women in child-bearing age were collected for 88 countries (29 European). The association between prevalence of toxoplasmosis and specific disease burden estimated with age-standardized Disability Adjusted Life Year (DALY) or with mortality, was calculated using General Linear Method with Gross Domestic Product per capita (GDP), geolatitude and humidity as covariates, and also using nonparametric partial Kendall correlation test with GDP as a covariate. The prevalence of toxoplasmosis correlated with specific disease burden in particular countries explaining 23% of variability in disease burden in Europe. The analyses revealed that for example, DALY of 23 of 128 analyzed diseases and disease categories on the WHO list showed correlations (18 positive, 5 negative) with prevalence of toxoplasmosis and another 12 diseases showed positive trends (p<0.1). For several obtained significant correlations between the seroprevalence of toxoplasmosis and specific diseases/clinical entities, possible pathophysiological, biochemical and molecular explanations are presented. Conclusions The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests however that possible role of toxoplasmosis as a triggering

  12. Value of Computerized Tomography Enterography in Predicting Crohn’s Disease Activity: Correlation with Crohn’s Disease Activity Index and C-Reactive Protein

    PubMed Central

    Park, Eun Kyung; Han, Na Yeon; Park, Beom Jin; Sung, Deuk Jae; Cho, Sung Beom; Jeen, Yoon Tae; Keum, Bora; Kim, Min Ju

    2016-01-01

    Background The accurate evaluation of Crohn’s disease activity is important for the treatment of the disease and for monitoring the response. Computerized tomography (CT) enterography is a useful imaging modality that reflects enteric inflammation, as well as extramural complications. Objectives The aim of this study was to evaluate the correlation between CT enterographic (CTE) findings of active Crohn’s disease and the Crohn’s disease activity index (CDAI) and C-reactive protein (CRP). Patients and Methods Fifty CT enterographies of 39 patients with Crohn’s disease in the small bowel were used in our study. The CDAI was assessed through clinical and laboratory variables. Multiple CT parameters, including mural hyperenhancement, mural thickness, mural stratification, comb sign, and mesenteric fat attenuation, were evaluated with a four-point scale. The presence or absence of enhanced lymph nodes, fibrofatty proliferation, sinus or fistula, abscess, and stricture were also assessed. Two gastrointestinal radiologists independently reviewed all CT images, and inter-observer agreement was examined. Correlations between CT findings, CRP, and CDAI were assessed using Spearman’s rank correlation and logistic regression analysis. To assess the predictive accuracy of the model, a receiver-operating characteristic curve analysis for the sum of CT enterographic scores was used. Results Mural hyperenhancement, mural thickness, comb sign, mesenteric fat density, and fibrofatty proliferation were significantly correlated with CDAI and CRP (P < 0.05). The binary logistic regression model demonstrated that mesenteric fat density, mural stratification, and the presence of enhanced lymph nodes (P < 0.05) had an influence on CDAI severity. The area under the receiver operating characteristic curve (AUROC) of the CTE index for predicting disease activity was 0.85. Using a cut-off value of 8, the sensitivity and negative predictive values were 95% and 94%, respectively

  13. Adenosine plasma level correlates with homocysteine and uric acid concentrations in patients with coronary artery disease.

    PubMed

    Fromonot, J; Deharo, P; Bruzzese, L; Cuisset, T; Quilici, J; Bonatti, S; Fenouillet, E; Mottola, G; Ruf, J; Guieu, R

    2016-03-01

    The role of hyperhomocysteinemia in coronary artery disease (CAD) patients remains unclear. The present study evaluated the relationship between homocysteine (HCys), adenosine plasma concentration (APC), plasma uric acid, and CAD severity evaluated using the SYNTAX score. We also evaluated in vitro the influence of adenosine on HCys production by hepatoma cultured cells (HuH7). Seventy-eight patients (mean age ± SD: 66.3 ± 11.3; mean SYNTAX score: 19.9 ± 12.3) and 30 healthy subjects (mean age: 61 ± 13) were included. We incubated HuH7 cells with increasing concentrations of adenosine and addressed the effect on HCys level in cell culture supernatant. Patients vs. controls had higher APC (0.82 ± 0.5 μmol/L vs 0.53 ± 0.14 μmol/L; p < 0.01), HCys (15 ± 7.6 μmol/L vs 6.8 ± 3 μmol/L, p < 0.0001), and uric acid (242.6 ± 97 vs 202 ± 59, p < 0.05) levels. APC was correlated with HCys and uric acid concentrations in patients (Pearson's R = 0.65 and 0.52; p < 0.0001, respectively). The SYNTAX score was correlated with HCys concentration. Adenosine induced a time- and dose-dependent increase in HCys in cell culture. Our data suggest that high APC is associated with HCys and uric acid concentrations in CAD patients. Whether the increased APC participates in atherosclerosis or, conversely, is part of a protective regulation process needs further investigations.

  14. Correlation between the different pH-metry scores in gastroesophageal reflux disease in children

    PubMed Central

    Lupu, Vasile Valeriu; Ignat, Ancuţa; Paduraru, Gabriela; Ciubara, Anamaria; Moscalu, Mihaela; Marginean, Cristina Oana; Burlea, Marin

    2016-01-01

    Abstract The 24-hour esophageal pH-metry is the most widely used method to diagnose the gastroesophageal reflux disease (GERD). The study compares the different scores obtained during the 24-hour esophageal pH-metry. A retrospective study over 5 years including 234 children (1 month and 18 years old) admitted in a pediatric gastroenterology regional center in Northeast Romania, with suspicion of GERD. They underwent 24- hour esophageal pH-metry, and the scores obtained (Boix-Ochoa, DeMeester, Johnson-DeMeester) were compared. Out of the 234 children, 172 (73.50%) had positive Boix-Ochoa score and 62 (26.50%) had normal Boix-Ochoa score (<11.99). Based on the DeMeester score, 149 children (63.68%) were positive and 85 (36.32%) were negative. The correlation of the Demeester score with the Boix-Ochoa score was very high (r = 0.978, P <  < 0.01, 95% confidence interval). Considering the Johnson-DeMeester score, 120 cases (51.28%) had GERD and 114 (48.72%) did not. The correlation of the Johnson-DeMeester score with the Boix-Ochoa score was still high (r = 0.94, P <  < 0.01, 95% 95% confidence interval). As considered until now, the Boix-Ochoa score is the most accurate score to be used in pediatrics for the diagnosis of GERD. The use of the different scores—Boix-Ochoa, DeMeester, Johnson-DeMeester—showed a high sensitivity and specificity of the pH-metry measurements applied to the study lot, but the last score has a higher risk of false-negative results. PMID:27367982

  15. Correlation of Levels of Oncostatin M Cytokine in Crevicular Fluid and Serum in Periodontal Disease

    PubMed Central

    Thorat, ManojKumar; AR, Pradeep; Garg, Garima

    2010-01-01

    Aim The aim of this study was to measure the level of Oncostatin M (OSM) a gp130 cytokine in the gingival crevicular fluid (GCF) and serum of chronic periodontitis patients and to find any correlation between them before and after periodontal therapy (scaling and root planing, SRP). Methodology 60 subjects (age 25–50 years) were enrolled into three groups (n=20 per group), group I (healthy), group II (gingivitis) and group III (chronic periodontitis). Group III subjects were followed for 6–8 weeks after the initial periodontal therapy (SRP) as the group IV (after periodontal therapy). Clinical parameters were assessed as gingival index (GI), probing depth (PD), clinical attachment level (CAL), and radiographic evidence of bone loss. GCF and serum levels of OSM were measured by using Enzyme Linked Immunosorbent Assay (ELISA). Results It was found that mean OSM levels had been elevated in both the GCF and serum of chronic periodontitis subjects (726.65 ± 283.56 and 65.59 ± 12.37 pg·mL−1, respectively) and these levels were decreased proportionally after the periodontal therapy (95.50 ± 38.85 and 39.98 ± 16.69 pg·mL−1 respectively). However, OSM was detected in GCF of healthy subjects (66.15 ± 28.10 pg·mL−1) and gingivitis-suffering subjects (128.33 ± 22.96 pg·mL−1) and was found as below the detectable limit (≈0.0 pg·mL−1) in the serum of same subjects. Significant correlation has been found between clinical parameters and GCF-serum levels of OSM. Conclusion Increased OSM level both in the GCF and serum, and the decreased levels after initial periodontal therapy (SRP) may suggest a use as an inflammatory bio-marker in the periodontal disease. PMID:21404969

  16. Caregiver Burden in Alzheimer’s Disease: Cross Sectional and Longitudinal Patient Correlates

    PubMed Central

    Mohamed, Somaia; Rosenheck, Robert; Lyketsos, Kostas; Schneider, Lon S.

    2014-01-01

    Objectives Alzheimer disease (AD) imposes a severe burden upon patients and their caregivers. Although there is substantial evidence of the adverse impact of burden, considerably less is known about its specific correlates and potential causes. Design We use data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)-AD study to examine the relationship of burden and depression among AD caregivers to patient and caregiver sociodemographic characteristics, patients’ cognitive status, psychiatric and behavioral symptoms, functional abilities, quality of life, and intensity of care provided by caregivers. Setting CATIE-AD included outpatients in usual care settings, and assessed treatment outcomes over nine-months. Participants Data were examined from 421 ambulatory outpatients with a diagnosis of dementia of the Alzheimer's type or probable AD with agitation or psychosis. Measures The Burden Interview, the Beck Depression Inventory, and the Caregiver Distress Scale were used to evaluate caregiver burden. Results More severe psychiatric and behavioral problems and decreased patient quality of life, as well as lower functional capability were significantly associated with higher levels of burden and depression among caregivers at baseline. Six month changes showed that decreased symptoms and improved quality of life were associated with decreased burden and accounted for most of the explained variance in change in burden measures. Conclusion Severity of psychiatric symptoms, behavioral disturbances and patients’ quality of life are the main correlates of caregivers’ experience burden. Psychosocial and pharmacologic interventions targeting these two aspects of the disorder are likely to not only alleviate patient suffering but also promote caregiver well-being. PMID:20808108

  17. Correlation analysis between ApoM gene-promoter polymorphisms and coronary heart disease

    PubMed Central

    Zhang, Yao; Huang, Li-Zhu; Liu, Yan; Yang, Qing-Ling; Zhou, Xin

    2016-01-01

    Summary Objectives: Apolipoprotein M (ApoM), a 25-kDa plasma protein belonging to the lipocalin protein family, is predominantly associated with high-density lipoprotein cholesterol (HDL-C). Studies have suggested ApoM to be important for the formation of pre-β-HDL and to increase cholesterol efflux from macrophage foam cells. The aim of this study was to explore the association of single-nucleotide polymorphisms(SNPs) in the ApoM promoter with coronary atherosclerotic disease (CAD), and the contribution of latent factors. Methods: ApoM was measured in samples from two separate case–control studies, of whom 88 patients developed CAD and 88 were controls. Whole-blood samples from subjects were genotyped by PCR-restriction fragment length polymorphism (PCR-RFLP). Luciferase activities were measured for HepG2 cells with two SNPs, rs805296 (T-778C) and rs940494 (T-855C), and after interfering with or overexpressing the predicted transcription factors. The ability of the SNPs to combine with nucleoproteins was analysed by electophoretic mobility shift assay (EMSA). Results: Mean plasma ApoM concentrations in the CAD and non-CAD groups were 9.58 ± 4.30 and 12.22 ± 6.59 μg/ ml, respectively. Correlation studies of ApoM concentrations with several analytes showed a marked positive correlation with HDL-C, fasting plasma glucose and triglyceride levels. The CC genotype showed lower luciferase activities compared to the TC and TT genotypes. The ApoM-855 mutant-typecould bind to the AP-2α. Interference and overexpression of AP-2 increased and decreased luciferase activities of the wild and mutant types to different degrees. Conclusion:: ApoM may be a biomarker of CAD. ApoM- 855 T→C substitution provides binding sites for AP-2α and reduces ApoM transcription activity. PMID:27841911

  18. Rapid Eye Movement Sleep Behavior Disorder Symptoms Correlate with Domains of Cognitive Impairment in Parkinson's Disease

    PubMed Central

    Zhang, Jin-Ru; Chen, Jing; Yang, Zi-Jiao; Zhang, Hui-Jun; Fu, Yun-Ting; Shen, Yun; He, Pei-Cheng; Mao, Cheng-Jie; Liu, Chun-Feng

    2016-01-01

    Background: Rapid eye movement (REM) sleep behavior disorder (RBD) may be a risk factor for cognitive impairment in patients with Parkinson's disease (PD). However, little is known regarding the relation between the severity of RBD and the different domains of cognitive impairment. The aim of this study was: (1) to investigate the domains of cognitive impairment in patients with PD and RBD, and (2) to explore risk factors for PD-mild cognitive impairment (PD-MCI) and the relationship between RBD severity and impairment in different cognitive domains in PD. Methods: The participants were grouped as follows: PD without RBD (PD-RBD; n = 42), PD with RBD (PD + RBD; n = 32), idiopathic RBD (iRBD; n = 15), and healthy controls (HCs; n = 36). All participants completed a battery of neuropsychological assessment of attention and working memory, executive function, language, memory, and visuospatial function. The information of basic demographics, diseases and medication history, and motor and nonmotor manifestations was obtained and compared between PD-RBD and PD + RBD groups. Particular attention was paid to the severity of RBD assessed by the RBD Questionnaire-Hong Kong (RBDQ-HK) and the RBD Screening Questionnaire (RBDSQ), then we further examined associations between the severity of RBD symptoms and cognitive levels via correlation analysis. Results: Compared to PD-RBD subjects, PD + RBD patients were more likely to have olfactory dysfunction and their Epworth Sleepiness Scale scores were higher (P < 0.05). During neuropsychological testing, PD + RBD patients performed worse than PD-RBD patients, including delayed memory function, especially. The MCI rates were 33%, 63%, 33%, and 8% for PD-RBD, PD + RBD, iRBD, and HC groups, respectively. RBD was an important factor for the PD-MCI variance (odds ratio = 5.204, P = 0.018). During correlation analysis, higher RBDSQ and RBDQ-HK scores were significantly associated with poorer performance on the Trail Making Test-B (errors

  19. Correlation Between Bladder Pain Syndrome/Interstitial Cystitis and Pelvic Inflammatory Disease

    PubMed Central

    Chung, Shiu-Dong; Chang, Chao-Hsiang; Hung, Peir-Haur; Chung, Chi-Jung; Muo, Chih-Hsin; Huang, Chao-Yuan

    2015-01-01

    Abstract Pelvic inflammatory disease (PID) has been investigated in Western countries and identified to be associated with chronic pelvic pain and inflammation. Bladder pain syndrome/interstitial cystitis (BPS/IC) is a complex syndrome that is significantly more prevalent in women than in men. Chronic pelvic pain is a main symptom of BPS/IC, and chronic inflammation is a major etiology of BPS/IC. This study aimed to investigate the correlation between BPS/IC and PID using a population-based dataset. We constructed a case–control study from the Taiwan National Health Insurance program. The case cohort comprised 449 patients with BPS/IC, and 1796 randomly selected subjects (about 1:4 matching) were used as controls. A Multivariate logistic regression model was constructed to estimate the association between BPS/IC and PID. Of the 2245 sampled subjects, a significant difference was observed in the prevalence of PID between BPS/IC cases and controls (41.7% vs 15.4%, P < 0.001). Multivariate logistic regression analysis revealed that the odds ratio (OR) for PID among cases was 3.69 (95% confidence interval [CI]: 2.89–4.71). Furthermore, the ORs for PID among BPS/IC cases were 4.52 (95% CI: 2.55–8.01), 4.31 (95% CI: 2.91–6.38), 3.00 (95% CI: 1.82–4.94), and 5.35 (95% CI: 1.88–15.20) in the <35, 35–49, 50–64, and >65 years age groups, respectively, after adjusting for geographic region, irritable bowel syndrome, and hypertension. Joint effect was also noted, specifically when patients had both PID and irritable bowel disease with OR of 10.5 (95% CI: 4.88–22.50). This study demonstrated a correlation between PID and BPS/IC. Clinicians treating women with PID should be alert to BPS/IC-related symptoms in the population. PMID:26579800

  20. Clinical Correlates of Mass Effect in Autosomal Dominant Polycystic Kidney Disease

    PubMed Central

    Kim, Hyunsuk; Park, Hayne Cho; Ryu, Hyunjin; Kim, Kiwon; Kim, Hyo Sang; Oh, Kook-Hwan; Yu, Su Jong; Chung, Jin Wook; Cho, Jeong Yeon; Kim, Seung Hyup; Cheong, Hae Il; Lee, Kyubeck; Park, Jong Hoon; Pei, York; Hwang, Young-Hwan; Ahn, Curie

    2015-01-01

    Mass effect from polycystic kidney and liver enlargement can result in significant clinical complications and symptoms in autosomal dominant polycystic kidney disease (ADPKD). In this single-center study, we examined the correlation of height-adjusted total liver volume (htTLV) and total kidney volume (htTKV) by CT imaging with hepatic complications (n = 461) and abdominal symptoms (n = 253) in patients with ADPKD. “Mass-effect” complications were assessed by review of medical records and abdominal symptoms, by a standardized research questionnaire. Overall, 91.8% of patients had 4 or more liver cysts on CT scans. Polycystic liver disease (PLD) was classified as none or mild (htTLV < 1,600 mL/m); moderate (1,600 ≤ htTLV <3,200 mL/m); and severe (htTLV ≥ 3,200 mL/m). The prevalence of moderate and severe PLD in our patient cohort was 11.7% (n = 54/461) and 4.8% (n = 22/461), respectively, with a female predominance in both the moderate (61.1%) and severe (95.5%) PLD groups. Pressure-related complications such as leg edema (20.4%), ascites (16.6%), and hernia (3.6%) were common, and patients with moderate to severe PLD exhibited a 6-fold increased risk (compared to no or mild PLD) for these complications in multivariate analysis. Similarly, abdominal symptoms including back pain (58.8%), flank pain (53.1%), abdominal fullness (46.5%), and dyspnea/chest-discomfort (44.3%) were very common, and patients with moderate to severe PLD exhibited a 5-fold increased risk for these symptoms. Moderate to severe PLD is a common and clinically important problem in ~16% of patients with ADPKD who may benefit from referral to specialized centers for further management. PMID:26641645

  1. Olfactory functions in patients with psoriasis vulgaris: correlations with the severity of the disease.

    PubMed

    Aydın, Ersin; Tekeli, Hakan; Karabacak, Ercan; Altunay, İlknur Kıvanç; Aydın, Çigdem; Çerman, Aslı Aksu; Altundağ, Aytuğ; Salihoğlu, Murat; Çayönü, Melih

    2016-08-01

    It is well known that psoriasis is not only limited to skin, but a systemic autoimmune disease with various comorbidities. Olfactory dysfunction, one of as a common but lesser known symptom of patients with autoimmune diseases, often presents with smell loss. The aim of this study was to assess the olfactory functions in patients with psoriasis and to compare with healthy controls. A total of 50 patients with psoriasis and 43 control subjects were included to the study. The clinical severity of psoriasis was calculated by psoriasis area and severity index (PASI). Patients were classified into two groups according to PASI score as mild (PASI ≤10) and moderate-severe (PASI >10). Olfactory function was evaluated with "Sniffin'Sticks" test. Total test scores (max. 48 points) of threshold, discrimination, and identification (TDI) were classified as normal olfaction = normosmia (>30.3 points), decreased olfaction = hyposmia (16.5-30.3 points) and loss of olfaction = anosmia (<16.5 points). Psoriasis patients had significantly lower smell scores compared with healthy controls (p < 0.001). Of the 50 psoriasis patients, 40 (80 %) were hyposmic. We found negative correlation between TDI and PASI (r = -0.34, p = 0.014). The TDI scores of the patients with moderate-severe psoriasis (PASI score >10) were found to be significantly lower than the patients with mild psoriasis (PASI ≤10) (p < 0.001). Olfactory dysfunction in patients with psoriasis could be thought as a comorbidity as in other inflammatory disorders. Physicians should be aware of olfactory impairment when evaluating psoriasis patients in their clinical practice.

  2. Sphingolipid Metabolism Correlates with Cerebrospinal Fluid Beta Amyloid Levels in Alzheimer’s Disease

    PubMed Central

    Fonteh, Alfred N.; Ormseth, Cora; Chiang, Jiarong; Cipolla, Matthew; Arakaki, Xianghong; Harrington, Michael G.

    2015-01-01

    Sphingolipids are important in many brain functions but their role in Alzheimer’s disease (AD) is not completely defined. A major limit is availability of fresh brain tissue with defined AD pathology. The discovery that cerebrospinal fluid (CSF) contains abundant nanoparticles that include synaptic vesicles and large dense core vesicles offer an accessible sample to study these organelles, while the supernatant fluid allows study of brain interstitial metabolism. Our objective was to characterize sphingolipids in nanoparticles representative of membrane vesicle metabolism, and in supernatant fluid representative of interstitial metabolism from study participants with varying levels of cognitive dysfunction. We recently described the recruitment, diagnosis, and CSF collection from cognitively normal or impaired study participants. Using liquid chromatography tandem mass spectrometry, we report that cognitively normal participants had measureable levels of sphingomyelin, ceramide, and dihydroceramide species, but that their distribution differed between nanoparticles and supernatant fluid, and further differed in those with cognitive impairment. In CSF from AD compared with cognitively normal participants: a) total sphingomyelin levels were lower in nanoparticles and supernatant fluid; b) levels of ceramide species were lower in nanoparticles and higher in supernatant fluid; c) three sphingomyelin species were reduced in the nanoparticle fraction. Moreover, three sphingomyelin species in the nanoparticle fraction were lower in mild cognitive impairment compared with cognitively normal participants. The activity of acid, but not neutral sphingomyelinase was significantly reduced in the CSF from AD participants. The reduction in acid sphingomylinase in CSF from AD participants was independent of depression and psychotropic medications. Acid sphingomyelinase activity positively correlated with amyloid β42 concentration in CSF from cognitively normal but not impaired

  3. Domains and correlates of clinical balance impairment associated with Huntington's disease.

    PubMed

    Jacobs, Jesse V; Boyd, James T; Hogarth, Penelope; Horak, Fay B

    2015-03-01

    This study sought to (a) determine the domains of clinical balance impairments associated with Huntington's disease (HD), and (b) evaluate associations between balance test scores and other disease-related impairments. Eighteen subjects with genetically definite HD and 17 age-matched control subjects were evaluated on the Mini-BESTest for their clinical balance impairments as well as the Unified HD Rating Scale (UHDRS) motor and total functional capacity scales, Activity-Specific Balance Confidence (ABC) Scale-short form, Montreal Cognitive Assessment (MoCA), and Symbol Digit Modalities Test (SDMT). Results showed that subjects with HD exhibited significantly lower total Mini-BESTest scores than subjects without HD (mean (95% CI)=76 (64-87)% with HD, 98 (96-99)% without HD; p=0.0011). Mini-BESTest item scores were significantly lower for subjects with HD on one-leg stance, postural responses, standing with eyes closed on foam, and dual-task timed up-and-go. Mini-BESTest scores significantly correlated with UHDRS motor (r(2)=0.68; p=0.00003) and total functional capacity (r(2)=0.75; p=0.000006) scores as well as with scores on the ABC short form (r(2)=0.45; p=0.0024), SDMT (r(2)=0.42; p=0.0036), and MoCA (r(2)=0.23; p=0.046) assessments. This study, therefore, demonstrates that balance impairments associated with HD span domains of anticipatory postural adjustments, postural responses, stance in challenging sensory conditions, and gait. Although preliminary, clinical balance impairment appears to be an efficient proxy evaluation of multiple HD-related factors due to associations with functional capacity, other motor impairments, balance confidence, and cognitive abilities.

  4. Environmental water chemistry and possible correlation with Kaschin-Beck Disease (KBD) in northwestern Sichuan, China.

    PubMed

    Shi, Zeming; Pan, Pujing; Feng, Yanwei; Kan, Zezhong; Li, Zhonghui; Wei, Fei

    2017-02-01

    During the past several decades, etiological and geochemical studies tend to link the Kaschin-Beck Disease (KBD) to the deficiency of some specific trace elements (e.g., selenium and iodine) in the environment; however the link has been proven inconclusive. In this work, we have investigated the relationship between KBD and the environment in a broader scope by examining comprehensively the chemistry of the surface waters in northwestern Sichuan, China, in relation to the KBD prevalence. The surface waters in the study area were found to be near neutral to slightly alkaline (pH6.70 to 8.85 with a mean of 7.91) and mostly soft (total hardness 35.2 to 314.3mg/L, mean 118.8mg/L) with low salinity (total dissolved solids (TDS) 44.5mg/L to 376.6mg/L, mean 146.6mg/L). The waters were dominated by cations Ca(2+) and Mg(2+) and anion HCO3(-); whereas the alkali metal ions K(+) and Na(+) and the anions Cl(-) and S04(2-) were relatively scarce. Spatially, the hardness/salinity of the surface waters exhibited a characteristic of being lower towards the center of the study area where most severe KBD endemic has been observed. Even though it is not conclusive at this stage, a correlation between KBD prevalence and the salinity/hardness of the surface waters of an area has been demonstrated. As a postulate, the long-term consumption of such low salinity waters may lead to a deficiency of some essential elements such as Ca, Mg, Se and I in humans, which may be a factor in inducing KBD. However, other factors such as high altitude and cold climate, poor nutrition and sanitary conditions may play an important role in the disease endemic.

  5. Clinical Correlates of Mass Effect in Autosomal Dominant Polycystic Kidney Disease.

    PubMed

    Kim, Hyunsuk; Park, Hayne Cho; Ryu, Hyunjin; Kim, Kiwon; Kim, Hyo Sang; Oh, Kook-Hwan; Yu, Su Jong; Chung, Jin Wook; Cho, Jeong Yeon; Kim, Seung Hyup; Cheong, Hae Il; Lee, Kyubeck; Park, Jong Hoon; Pei, York; Hwang, Young-Hwan; Ahn, Curie

    2015-01-01

    Mass effect from polycystic kidney and liver enlargement can result in significant clinical complications and symptoms in autosomal dominant polycystic kidney disease (ADPKD). In this single-center study, we examined the correlation of height-adjusted total liver volume (htTLV) and total kidney volume (htTKV) by CT imaging with hepatic complications (n = 461) and abdominal symptoms (n = 253) in patients with ADPKD. "Mass-effect" complications were assessed by review of medical records and abdominal symptoms, by a standardized research questionnaire. Overall, 91.8% of patients had 4 or more liver cysts on CT scans. Polycystic liver disease (PLD) was classified as none or mild (htTLV < 1,600 mL/m); moderate (1,600 ≤ htTLV <3,200 mL/m); and severe (htTLV ≥ 3,200 mL/m). The prevalence of moderate and severe PLD in our patient cohort was 11.7% (n = 54/461) and 4.8% (n = 22/461), respectively, with a female predominance in both the moderate (61.1%) and severe (95.5%) PLD groups. Pressure-related complications such as leg edema (20.4%), ascites (16.6%), and hernia (3.6%) were common, and patients with moderate to severe PLD exhibited a 6-fold increased risk (compared to no or mild PLD) for these complications in multivariate analysis. Similarly, abdominal symptoms including back pain (58.8%), flank pain (53.1%), abdominal fullness (46.5%), and dyspnea/chest-discomfort (44.3%) were very common, and patients with moderate to severe PLD exhibited a 5-fold increased risk for these symptoms. Moderate to severe PLD is a common and clinically important problem in ~16% of patients with ADPKD who may benefit from referral to specialized centers for further management.

  6. Correlation between water hardness and cardiovascular diseases in Mostar city, Bosnia and Herzegovina.

    PubMed

    Knezović, Nevenka J; Memić, Mustafa; Mabić, Mirela; Huremović, Jasna; Mikulić, Ivanka

    2014-12-01

    The aim of this study was to determine the association of cardiovascular disease (CVD) of selected human subjects with the hardness of water they consume. Laboratory testing of physical and chemical parameters of water were made using standardized methods: Standard Methods 19th edn, 1995 (APHA, AWWA & WEF, Washington, DC), and ISO 7888:1985, ISO 10523:1998. Pearson's chi-squared test was used for the statistical analysis of data, with the significance level of 0.05. The obtained data were analysed using the statistical program SPSS 16.0. The study sample consisted of 1,021 individuals divided into two groups: soft water consumers, 603 individuals, and, hard water consumers, 618 individuals. Results indicate that a statistically significant (χ(2) = 5.315; df = 1; p = 0.021) number of individuals with CVD drink soft water. The prevalence of CVD in the age group 45-60 years in the study area where soft water is consumed was 21.3% and in the study area where hard water is consumed the prevalence of CVD was 13.7%. The summary results indicate significant correlation between the prevalence of CVD in the population group who drink soft water. The value of the relative risk is 1.127.

  7. Intravascular lymphoma: magnetic resonance imaging correlates of disease dynamics within the central nervous system

    PubMed Central

    Baehring, J; Henchcliffe, C; Ledezma, C; Fulbright, R; Hochberg, F

    2005-01-01

    Background: Intravascular lymphoma (IVL) is a rare non-Hodgkin's lymphoma with relative predilection for the central nervous system. In the absence of extraneural manifestations, the disease is not recognised until autopsy in the majority of cases underlining the need for new clinical markers. Methods: This is a retrospective series of five patients with IVL seen at a single institution over three years. An advanced magnetic resonance imaging (MRI) protocol was performed at various time points prior to diagnosis and during treatment. Results: MRI revealed multiple lesions scattered throughout the cerebral hemispheres; the brainstem, cerebellum, and spinal cord were less frequently involved. On initial presentation, hyperintense lesions were seen on diffusion weighted images suggestive of ischaemia in three of four patients in whom the images were obtained at that time point. In four patients lesions were also identifiable as hyperintense areas on fluid attenuated inversion recovery (FLAIR) sequences. Initial contrast enhancement was encountered in three cases. Diffusion weighted imaging lesions either vanished or followed the typical pattern of an ischaemic small vessel stroke with evolution of abnormal FLAIR signal followed by enhancement with gadolinium in the subacute stage and tissue loss in the chronic stage. Diffusion weighted imaging and FLAIR abnormalities proved to be partially reversible, correlating with the response to chemotherapy. Conclusion: We provide the first detailed description of the dynamic pattern of diffusion weighted MRI in IVL. These patterns in combination with systemic findings may facilitate early diagnosis and serve as a new tool to monitor treatment response. PMID:15774442

  8. Optimal control problem in correlation between smoking and epidemic of respiratory diseases

    NASA Astrophysics Data System (ADS)

    Aldila, D.; Apri, M.

    2014-02-01

    Smoking appears to be a risk factor that may increase the number of different pulmonary infections. This link is likely to be mediated by smoking adverse effects on the respiratory defenses. A mathematical model to describe correlation between the number of smokers and its effect on the number of infected people suffer from respiratory disease like influenza is constructed in this paper. Promotion of healthy life is accounted in the model as an optimal control problem to reduce the number of smokers. In this work, the transition rates from smokers to non-smokers and from non-smokers to smokers are regarded as the control variables. Assuming the control variables are constant, equilibrium points of the model can be obtained analytically. The basic reproductive ratio as the endemic threshold is taken from the spectral radius of the next-generation matrix. Using numerical simulation, we show that the healthy life promotion can reduce the number of infected person significantly by reducing the number of smokers. Furthermore, different initial conditions to show different situations in the field are also simulated. It is shown that a large effort to increase the transition rate from smokers to non-smokers and to reduce the transition from non-smokers to smokers should be applied in the endemic reduction scenario.

  9. Rab6 is increased in Alzheimer's disease brain and correlates with endoplasmic reticulum stress.

    PubMed

    Scheper, W; Hoozemans, J J M; Hoogenraad, C C; Rozemuller, A J M; Eikelenboom, P; Baas, F

    2007-10-01

    Alzheimer's disease (AD) is characterized by deposits of aggregated proteins. Accumulation of aggregation-prone proteins activates protein quality control mechanisms, such as the unfolded protein response (UPR) in the endoplasmic reticulum (ER). We previously reported upregulation of the UPR marker BiP in AD brain. In this study, we investigated the small GTPase Rab6, which is involved in retrograde Golgi-ER trafficking and may function as a post-ER quality control system. Using immunohistochemistry and semiquantitative Western blotting, the expression of Rab6 was analysed in hippocampus, entorhinal and temporal cortex of 10 AD patients and six nondemented control subjects. Rab6 is upregulated in AD temporal cortex from Braak stage 3/4, the same stage that UPR activation is found. We observe increased neuronal Rab6 immunoreactivity in all brain areas examined. Although some neurones show colocalization of immunoreactivity for Rab6 and hyperphosphorylated tau, strong Rab6 staining does not colocalize with tangles. We find a highly significant correlation between the Rab6 and BiP levels. In vitro data show that Rab6 is not upregulated as a result of UPR activation or proteasome inhibition indicating an independent regulatory mechanism. Our data suggest that ER and post-ER protein quality control mechanisms are activated early in the pathology of AD.

  10. Growth Patterns of Clostridium difficile – Correlations with Strains, Binary Toxin and Disease Severity: A Prospective Cohort Study

    PubMed Central

    Tschudin-Sutter, Sarah; Braissant, Olivier; Erb, Stefan; Stranden, Anne; Bonkat, Gernot; Frei, Reno; Widmer, Andreas F.

    2016-01-01

    A broad spectrum of symptoms has been associated with C. difficile infection (CDI). Several studies indicate that toxin-production correlates with growth rates of C. difficile. This study aimed to correlate growth rates of C. difficile with disease severity and strain characteristics. From 01/2003 to 10/2011, strains from a prospective cohort of all inpatients with CDI at the University Hospital Basel, Switzerland were analyzed regarding binary toxin, presence of the tcdC deletion and ribotype. Isothermal microcalorimetry was performed to determine growth rates, quantified by the Gompertz function. Ordered logistic regression models were used to correlate disease severity with strain features and clinical characteristics. Among 199 patients, 31 (16%) were infected with binary toxin-producing strains, of which the tcdC gene-deletion nt117 was detected in 9 (4%). Disease severity was classified as mild in 130 patients (65.3%), as severe in 59 patients (29.7%) and as severe/complicated in 10 patients (5.0%). Growth rates were inversely associated with disease severity in univariable (OR 0.514, 95%CI 0.29–0.91, p = 0.023) and multivariable analyses (OR 0.51, 95%CI 0.26–0.97, p = 0.040). While none of the strain characteristics such as presence of the tcdC gene deletion or binary toxin predicted CDI severity, growth rates were inversely correlated with disease severity. Further investigations are needed to analyze growth-regulators and respective correlations with the level of toxin production in C. difficile, which may be important determinants of disease severity. PMID:27598309

  11. Disease severity and viral load are correlated in infants with primary respiratory syncytial virus infection in the community.

    PubMed

    Houben, M L; Coenjaerts, F E J; Rossen, J W A; Belderbos, M E; Hofland, R W; Kimpen, J L L; Bont, L

    2010-07-01

    Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, with remarkable variability in disease severity. Factors determining severity of disease in previously healthy infants are still unclear. It was hypothesized that disease severity is correlated with viral load in primary RSV infection. Infants of a healthy birth cohort were included at signs of their first respiratory tract infection. Nasopharyngeal aspirate was obtained within 48-96 hr and disease severity was assessed with a previously published severity scoring model. PCR was applied to test the aspirates in a semi-quantitative way for the presence of 10 respiratory pathogens. In case of multiple infection, the pathogen with the highest load was defined as the primary pathogen. The correlation between disease severity and viral load was analyzed. A total of 82 infants were included over a period of 2 years. Median age at first respiratory tract infection was 3 months. Pathogens were detected in 77 (94%) infants; more than one pathogen was detected in 35 (43%) infants. RSV was present in aspirates of 30 infants; in 16 aspirates RSV was the primary pathogen. A negative correlation between RSV CT-value and disease severity was found in all RSV cases (rho = -0.52, P = 0.003) and in cases with RSV as the primary pathogen (rho = -0.54, P = 0.03). In conclusion, this is the first report on viral loads in previously healthy infants with RSV infection in the community. Disease severity correlated positively with viral load during primary RSV infection.

  12. Inflammatory cytokine levels correlate with amyloid load in transgenic mouse models of Alzheimer's disease

    PubMed Central

    Patel, Nikunj S; Paris, Daniel; Mathura, Venkatarajan; Quadros, Amita N; Crawford, Fiona C; Mullan, Michael J

    2005-01-01

    Background Inflammation is believed to play an important role in the pathology of Alzheimer's disease (AD) and cytokine production is a key pathologic event in the progression of inflammatory cascades. The current study characterizes the cytokine expression profile in the brain of two transgenic mouse models of AD (TgAPPsw and PS1/APPsw) and explores the correlations between cytokine production and the level of soluble and insoluble forms of Aβ. Methods Organotypic brain slice cultures from 15-month-old mice (TgAPPsw, PS1/APPsw and control littermates) were established and multiple cytokine levels were analyzed using the Bio-plex multiple cytokine assay system. Soluble and insoluble forms of Aβ were quantified and Aβ-cytokine relationships were analyzed. Results Compared to control littermates, transgenic mice showed a significant increase in the following pro-inflammatory cytokines: TNF-α, IL-6, IL-12p40, IL-1β, IL-1α and GM-CSF. TNF-α, IL-6, IL-1α and GM-CSF showed a sequential increase from control to TgAPPsw to PS1/APPsw suggesting that the amplitude of this cytokine response is dependent on brain Aβ levels, since PS1/APPsw mouse brains accumulate more Aβ than TgAPPsw mouse brains. Quantification of Aβ levels in the same slices showed a wide range of Aβ soluble:insoluble ratio values across TgAPPsw and PS1/APPsw brain slices. Aβ-cytokine correlations revealed significant relationships between Aβ1–40, 1–42 (both soluble and insoluble) and all the above cytokines that changed in the brain slices. Conclusion Our data confirm that the brains of transgenic APPsw and PS1/APPsw mice are under an active inflammatory stress, and that the levels of particular cytokines may be directly related to the amount of soluble and insoluble Aβ present in the brain suggesting that pathological accumulation of Aβ is a key driver of the neuroinflammatory response. PMID:15762998

  13. Amyloid Beta-Mediated Hypomethylation of Heme Oxygenase 1 Correlates with Cognitive Impairment in Alzheimer's Disease.

    PubMed

    Sung, Hye Youn; Choi, Byung-Ok; Jeong, Jee Hyang; Kong, Kyoung Ae; Hwang, Jinha; Ahn, Jung-Hyuck

    2016-01-01

    To identify epigenetically regulated genes involved in the pathogenesis of Alzheimer's disease (AD) we analyzed global mRNA expression and methylation profiles in amyloid precursor protein (APP)-Swedish mutant-expressing AD model cells, H4-sw and selected heme oxygenase-1 (HMOX1), which is associated with pathological features of AD such as neurofibrillary tangles and senile plaques. We examined the epigenetic regulatory mechanism of HMOX1 and its application as a diagnostic and prognostic biomarker for AD. Our results show that HMOX1 mRNA and protein expression was approximately 12.2-fold and 7.9-fold increased in H4-sw cells, respectively. Increased HMOX1 expression was also detected in the brain, particularly the hippocampus, of AD model transgenic mice. However, the methylation of specific CpG sites within its promoter, particularly at CpG located -374 was significantly decreased in H4-sw cells. Treatment of neuroglioma cells with the demethylating agent 5-aza-2'-deoxycytidine resulted in reduced methylation of HMOX1 promoter accompanied by enhanced HMOX1 expression strongly supporting DNA methylation-dependent transcriptional regulation of HMOX1. Toxic Aβ-induced aberrant hypomethylation of HMOX1 at -374 promoter CpG site was correlated with increased HMOX1 expression. In addition to neuroglioma cells, we also found Aβ-induced epigenetic regulation of HMOX1 in human T lymphocyte Jurkat cells. We evaluated DNA methylation status of HMOX1 at -374 promoter CpG site in blood samples from AD patients, patients with mild cognitive impairment (MCI), and control individuals using quantitative methylation-specific polymerase chain reaction. We observed lower methylation of HMOX1 at the -374 promoter CpG site in AD patients compared to MCI and control individuals, and a correlation between Mini-Mental State Examination score and demethylation level. Receiver operating characteristics analysis revealed good discrimination of AD patients from MCI patients and control

  14. The ratio of N-acetyl aspartate to glutamate correlates with disease duration of amyotrophic lateral sclerosis.

    PubMed

    Sako, Wataru; Abe, Takashi; Izumi, Yuishin; Harada, Masafumi; Kaji, Ryuji

    2016-05-01

    Glutamate (Glu)-induced excitotoxicity has been implicated in the neuronal loss of amyotrophic lateral sclerosis. To test the hypothesis that Glu in the primary motor cortex contributes to disease severity and/or duration, the Glu level was investigated using MR spectroscopy. Seventeen patients with amyotrophic lateral sclerosis were diagnosed according to the El Escorial criteria for suspected, possible, probable or definite amyotrophic lateral sclerosis, and enrolled in this cross-sectional study. We measured metabolite concentrations, including N-acetyl aspartate (NAA), creatine, choline, inositol, Glu and glutamine, and performed partial correlation between each metabolite concentration or NAA/Glu ratio and disease severity or duration using age as a covariate. Considering our hypothesis that Glu is associated with neuronal cell death in amyotrophic lateral sclerosis, we investigated the ratio of NAA to Glu, and found a significant correlation between NAA/Glu and disease duration (r=-0.574, p=0.02). The "suspected" amyotrophic lateral sclerosis patients showed the same tendency as possible, probable and definite amyotrophic lateral sclerosis patients in regard to correlation of NAA/Glu ratio with disease duration. The other metabolites showed no significant correlation. Our findings suggested that glutamatergic neurons are less vulnerable compared to other neurons and this may be because inhibitory receptors are mainly located presynaptically, which supports the notion of Glu-induced excitotoxicity.

  15. Correlations Between the Incidence of National Notifiable Infectious Diseases and Public Open Data, Including Meteorological Factors and Medical Facility Resources

    PubMed Central

    Jang, Jin-Hwa; Lee, Ji-Hae; Je, Mi-Kyung; Cho, Myeong-Ji; Bae, Young Mee; Son, Hyeon Seok; Ahn, Insung

    2015-01-01

    Objectives: This study was performed to investigate the relationship between the incidence of national notifiable infectious diseases (NNIDs) and meteorological factors, air pollution levels, and hospital resources in Korea. Methods: We collected and stored 660 000 pieces of publicly available data associated with infectious diseases from public data portals and the Diseases Web Statistics System of Korea. We analyzed correlations between the monthly incidence of these diseases and monthly average temperatures and monthly average relative humidity, as well as vaccination rates, number of hospitals, and number of hospital beds by district in Seoul. Results: Of the 34 NNIDs, malaria showed the most significant correlation with temperature (r=0.949, p<0.01) and concentration of nitrogen dioxide (r=-0.884, p<0.01). We also found a strong correlation between the incidence of NNIDs and the number of hospital beds in 25 districts in Seoul (r=0.606, p<0.01). In particular, Geumcheon-gu was found to have the lowest incidence rate of NNIDs and the highest number of hospital beds per patient. Conclusions: In this study, we conducted a correlational analysis of public data from Korean government portals that can be used as parameters to forecast the spread of outbreaks. PMID:26265666

  16. Quality of life of dogs with skin disease and of their owners. Part 2: administration of a questionnaire in various skin diseases and correlation to efficacy of therapy.

    PubMed

    Noli, Chiara; Colombo, Silvia; Cornegliani, Luisa; Ghibaudo, Giovanni; Persico, Paola; Vercelli, Antonella; Galzerano, Mario

    2011-08-01

    A previously validated 15-item questionnaire on dogs' life quality (QoL1) and that of their owners (QoL2) was applied in a multicentre study to owners of 200 dogs with different dermatological conditions, together with a question on the owner-perceived disease severity (S). Factor analysis was applied to the whole questionnaire. The correlation of S with QoL1 and QoL2 scores was evaluated using Spearman's rank correlation tests. Owner sex, age, educational level and willingness to pay for a potential definitive cure of the disease were recorded, and compared with quality of life (QoL) scores. In 23 atopic dogs, CADESI-03, pruritus Visual Analogue Scale and QoL scores were obtained before and after therapy, and their correlation was evaluated with linear regression. Factor analysis revealed that three factors (S, QoL1 and QoL2) explained 75% of the variance. Owner-perceived severity correlated significantly with QoL1 and QoL2 (P = 0.002 and P = 0.015, respectively). The five diseases with the worst QoL scores were scabies, pododermatitis, complicated atopic dermatitis, pemphigus foliaceus and endocrine alopecia. Pruritic diseases did not give significantly higher QoL1 or QoL2 scores compared with nonpruritic diseases (P = 0.19, Kruskall-Wallis test). Owner sex, age or educational level did not influence QoL scores. Female sex, a younger age and a higher educational level were significantly associated with more willingness to pay. In atopic dogs, all the scores decreased after therapy, but post-treatment CADESI-03 and Visual Analogue Scale scores did not correlate with QoL1 and QoL2. Questions related to the burden of maintenance therapy showed the lowest improvements in score.

  17. ADAMTS-13 metalloprotease abnormalities in systemic lupus erythematosus: is there a correlation with disease status?

    PubMed

    Klonizakis, P; Tselios, K; Sarantopoulos, A; Gougourellas, I; Rouka, E; Onufriadou, Z; Kapali, P; Kyriakou, D; Boura, P

    2013-04-01

    To clarify the role of ADAMTS-13 in the pathogenesis of thrombotic microangiopathy in systemic lupus erythematosus (SLE) we evaluated ADAMTS-13 profile (metalloprotease antigen levels, anti-ADAMTS-13 autoantibody levels, activity) in distinct patient groups according to disease activity, extent of cumulative tissue damage and history of antiphospholipid syndrome or end-organ damage. Forty-one lupus patients were analysed. ADAMTS-13 metalloprotease antigen levels and anti-ADAMTS-13 autoantibodies were evaluated by ELISA. ADAMTS-13 activity was measured by Fluorescence resonance energy transfer (FRET) technique. ADAMTS-13 metalloprotease antigen levels were significantly decreased in patients with Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) >1 (p<0.05). ADAMTS-13 metalloprotease antigen levels also exhibited a significant inverse correlation with anti-dsDNA levels (r= -0.60, p<0.05). Anti-ADAMTS-13 autoantibodies were marginally higher in patients with positive anti-dsDNA (p=0.08). Additionally, patients with positive anti-ADAMTS-13 autoantibodies exhibited the lowest activity levels (p<0.05). To our knowledge ADAMTS-13 profile in SLE has not been studied in regard to composite structured indices. The results of this study suggest that in patients with active SLE or considerable cumulative tissue damage, ADAMTS-13 levels may be decreased and anti-ADAMTS-13 autoantibodies may partially mediate this reduction. Further evaluation of ADAMTS-13 profile may explain its role in the pathogenesis of thrombotic microangiopathy in lupus patients and reveal a potential prognostic marker of microthrombotic manifestations in SLE.

  18. Disruption of pupil size modulation correlates with voluntary motor preparation deficits in Parkinson's disease.

    PubMed

    Wang, Chin-An; McInnis, Hailey; Brien, Donald C; Pari, Giovanna; Munoz, Douglas P

    2016-01-08

    Pupil size is an easy-to-measure, non-invasive method to index various cognitive processes. Although a growing number of studies have incorporated measures of pupil size into clinical investigation, there have only been limited studies in Parkinson's disease (PD). Convergent evidence has suggested PD patients exhibit cognitive impairment at or soon after diagnosis. Here, we used an interleaved pro- and anti-saccade paradigm while monitoring pupil size with saccadic eye movements to examine the relationship between executive function deficits and pupil size in PD patients. Subjects initially fixated a central cue, the color of which instructed them to either look at a peripheral stimulus automatically (pro-saccade) or suppress the automatic response and voluntarily look in the opposite direction of the stimulus (anti-saccade). We hypothesized that deficits of voluntary control should be revealed not only on saccadic but also on pupil responses because of the recently suggested link between the saccade and pupil control circuits. In elderly controls, pupil size was modulated by task preparation, showing larger dilation prior to stimulus appearance in preparation for correct anti-saccades, compared to correct pro-saccades, or erroneous pro-saccades made in the anti-saccade condition. Moreover, the size of pupil dilation correlated negatively with anti-saccade reaction times. However, this profile of pupil size modulation was significantly blunted in PD patients, reflecting dysfunctional circuits for anti-saccade preparation. Our results demonstrate disruptions of modulated pupil responses by voluntary movement preparation in PD patients, highlighting the potential of using low-cost pupil size measurement to examine executive function deficits in early PD.

  19. Endogenous nitric oxide in patients with stable COPD: correlates with severity of disease

    PubMed Central

    Clini, E.; Bianchi, L.; Pagani, M.; Ambrosino, N.

    1998-01-01

    BACKGROUND—Increased levels of exhaled nitric oxide (eNO) have been reported in asthmatic subjects but little information is available on eNO in patients with advanced chronic obstructive pulmonary disease (COPD). A study was undertaken to evaluate the levels of eNO in patients with stable COPD of different degrees of severity.
METHODS—Peak and plateau values of eNO (PNO and PLNO, respectively) were evaluated in 53 patients with COPD and analysed according to the level of forced expiratory volume in one second (FEV1) and the presence of cor pulmonale (CP) (group 1, FEV1 <35% predicted with CP, n = 15; group 2, FEV1 <35% predicted without CP, n =15; group 3, FEV1 >35% predicted, n = 23). Seventeen normal subjects served as controls.
RESULTS—All the patients with COPD had reduced levels of PLNO compared with the controls (mean (SD) 6.3 (3.0) and 9.4 (2.8) ppb, respectively). In groups 1 and 2 PLNO levels were significantly lower than in subjects in group 3 (5.5 (2.9), 5.7 (3.5), and 7.1 (2.7) ppb, respectively; p<0.01 ANOVA). In all subjects % predicted FEV1 correlated slightly with PLNO but not with PNO.
CONCLUSION—Patients with severe stable COPD have reduced levels of eNO compared with normal subjects. eNO levels are slightly related to the severity of airflow obstruction.

 PMID:10193378

  20. Correlates and heritability of nonalcoholic fatty liver disease in a minority cohort.

    PubMed

    Wagenknecht, Lynne E; Scherzinger, Ann L; Stamm, Elizabeth R; Hanley, Anthony J G; Norris, Jill M; Chen, Yii-Der I; Bryer-Ash, Michael; Haffner, Steven M; Rotter, Jerome I

    2009-06-01

    Nonalcoholic fatty liver disease (NAFLD) is associated with obesity and insulin resistance. The condition disproportionately affects Hispanic Americans. The aims of this study were to examine the risk factors and heritability of NAFLD in 795 Hispanic American and 347 African-American adults participating in the Insulin Resistance Atherosclerosis Study (IRAS) Family Study. Computed tomography (CT) scans of the abdomen were evaluated centrally for measures of liver-spleen (LS) density ratio and abdominal fat distribution. Other measures included insulin sensitivity (SI) calculated from a frequently sampled intravenous glucose tolerance test and various laboratory measures. Statistical models which adjust for familial relationships were estimated separately for the two ethnic groups. Heritability was calculated using a variance components approach. The mean age of the cohort was 49 years (range 22-84); 66% were female. NAFLD (LS ratio<1) was more common in Hispanic Americans (24%) than African Americans (10%). NAFLD was independently associated with SI and visceral adipose tissue (VAT) area in both ethnic groups, although the proportion of explained variance was considerably higher in the Hispanic models. Adiponectin contributed significantly in the African-American models whereas triglycerides (TGs) and plasminogen activator inhibitor 1 (PAI-1) contributed only in the Hispanic models. Liver density was modestly heritable in both ethnic groups (h2 approximately 0.35). In summary, the prevalence of NAFLD was twofold greater in Hispanic than African Americans. Certain correlates of NAFLD were similar between the ethnic groups, whereas others were distinct. NAFLD was modestly heritable. These findings suggest that NAFLD may have a differing environmental and/or genetic basis in these ethnic groups.

  1. Comprehensive Shoulder US Examination: A Standardized Approach with Multimodality Correlation for Common Shoulder Disease.

    PubMed

    Lee, Matthew H; Sheehan, Scott E; Orwin, John F; Lee, Kenneth S

    2016-10-01

    Shoulder pain is one of the most common musculoskeletal conditions encountered in primary care and specialty orthopedic clinic settings. Although magnetic resonance (MR) imaging is typically the modality of choice for evaluating the soft-tissue structures of the shoulder, ultrasonography (US) is becoming an important complementary imaging tool in the evaluation of superficial soft-tissue structures such as the rotator cuff, subacromial-subdeltoid bursa, and biceps tendon. The advantages of US driving its recent increased use include low cost, accessibility, and capability for real-time high-resolution imaging that enables dynamic assessment and needle guidance. As more radiologists are considering incorporating shoulder US into their practices, the development of a standardized approach to performing shoulder US should be a priority to facilitate the delivery of high-quality patient care. Familiarity with and comfort in performing a standardized shoulder US examination, as well as knowledge of the types of anomalies that can be evaluated well with US, will enhance the expertise of those working in musculoskeletal radiology practices and add value in the form of increased patient and health care provider satisfaction. This review describes the utility and benefits of shoulder US as a tool that complements MR imaging in the assessment of shoulder pain. A standardized approach to the shoulder US examination is also described, with a review of the basic technique of this examination, normal anatomy of the shoulder, common indications for shoulder US, and characteristic US findings of common shoulder diseases-with select MR imaging and arthroscopic correlation. Online supplemental material is available for this article. (©)RSNA, 2016.

  2. Brain–blood amino acid correlates following protein restriction in murine maple syrup urine disease

    PubMed Central

    2014-01-01

    Background Conventional therapy for patients with maple syrup urine disease (MSUD) entails restriction of protein intake to maintain acceptable levels of the branched chain amino acid, leucine (LEU), monitored in blood. However, no data exists on the correlation between brain and blood LEU with protein restriction, and whether correction in blood is reflected in brain. Methods To address this question, we fed intermediate MSUD mice diets of 19% (standard) and 6% protein, with collection of sera (SE), striata (STR), cerebellum (CE) and cortex (CTX) for quantitative amino acid analyses. Results LEU and valine (VAL) levels in all brain regions improved on average 28% when shifting from 19% to 6% protein, whereas the same improvements in SE were on average 60%. Isoleucine (ILE) in brain regions did not improve, while the SE level improved 24% with low-protein consumption. Blood-branched chain amino acids (LEU, ILE, and VAL in sera (SE)) were 362-434 μM, consistent with human values considered within control. Nonetheless, numerous amino acids in brain regions remained abnormal despite protein restriction, including glutamine (GLN), aspartate (ASP), glutamate (GLU), gamma-aminobutyric acid (GABA), asparagine (ASN), citrulline (CIT) and serine (SER). To assess the specificity of these anomalies, we piloted preliminary studies in hyperphenylalaninemic mice, modeling another large neutral aminoacidopathy. Employing an identical dietary regimen, we found remarkably consistent abnormalities in GLN, ASP, and GLU. Conclusions Our results suggest that blood amino acid analysis may be a poor surrogate for assessing the outcomes of protein restriction in the large neutral amino acidopathies, and further indicate that chronic neurotransmitter disruptions (GLU, GABA, ASP) may contribute to long-term neurocognitive dysfunction in these disorders. PMID:24886632

  3. Plasma Uromodulin Correlates With Kidney Function and Identifies Early Stages in Chronic Kidney Disease Patients

    PubMed Central

    Steubl, Dominik; Block, Matthias; Herbst, Victor; Nockher, Wolfgang Andreas; Schlumberger, Wolfgang; Satanovskij, Robin; Angermann, Susanne; Hasenau, Anna-Lena; Stecher, Lynne; Heemann, Uwe; Renders, Lutz; Scherberich, Jürgen

    2016-01-01

    Abstract Uromodulin, released from tubular cells of the ascending limb into the blood, may be associated with kidney function. This work studies the relevance of plasma uromodulin as a biomarker for kidney function in an observational cohort of chronic kidney disease (CKD) patients and subjects without CKD (CKD stage 0). It should be further evaluated if uromodulin allows the identification of early CKD stages. Plasma uromodulin, serum creatinine, cystatin C, blood-urea-nitrogen (BUN) concentrations, and estimated glomerular filtration rate (eGFR CKD-EPIcrea-cystatin) were assessed in 426 individuals of whom 71 were CKD stage 0 and 355 had CKD. Besides descriptive statistics, univariate correlations between uromodulin and biomarkers/eGFR were calculated using Pearson-correlation coefficient. Multiple linear regression modeling was applied to establish the association between uromodulin and eGFR adjusted for demographic parameters and pharmacologic treatment. Receiver-operating-characteristic (ROC) analysis adjusted for demographic parameters was performed to test if uromodulin allows differentiation of subjects with CKD stage 0 and CKD stage I. Mean uromodulin plasma levels were 85.7 ± 60.5 ng/mL for all CKD stages combined. Uromodulin was correlated with all biomarkers/eGFR in univariate analysis (eGFR: r = 0.80, creatinine: r = −0.76, BUN: r = −0.72, and cystatin C: r = −0.79). Multiple linear regression modeling showed significant association between uromodulin and eGFR (coefficient estimate β = 0.696, 95% confidence interval [CI] 0.603–0.719, P < 0.001). In ROC analysis uromodulin was the only parameter that significantly improved a model containing demographic parameters to differentiate between CKD 0° and I° (area under the curve [AUC] 0.831, 95% CI 0.746–0.915, P = 0.008) compared to creatinine, cystatin C, BUN, and eGFR (AUC for creatinine: 0.722, P = 0.056, cystatin C: 0.668, P = 0.418, BUN: 0.653, P

  4. Mother-daughter correlation of central obesity and other noncommunicable disease risk factors: Tehran Lipid and Glucose Study.

    PubMed

    Heidari, Zahra; Hosseinpanah, Farhad; Barzin, Maryam; Safarkhani, Maryam; Azizi, Fereidoun

    2015-03-01

    This study aimed to investigate the mother-daughter correlation for central obesity and other noncommunicable disease risk factors. The authors used metabolic and anthropometric data from the Tehran Lipid and Glucose Study, enrolling 1041 mother-daughter pairs for the current study. Three age strata were defined: 3 to 9 years for childhood (146 mother-daughter pairs), 10 to 17 years for adolescence (395 mother-daughter pairs), and 18 to 25 years for early adulthood (500 mother-daughter pairs). Familial associations for central obesity and other noncommunicable disease risk factors were assessed. The prevalence of central obesity was 44.7% in mothers and 11.2% in daughters (6.2% in the 3-9, 19.2% in the 10-17, and 6.4% in the 18-25 years groups). Mothers with central obesity were more likely than nonobese mothers to have daughters with central obesity (10.5% and 1.7%, respectively; P = .0001). Central obesity indices among daughters were positively correlated with those of their mothers in all 3 age strata. Correlations for other noncommunicable disease risk factors were analyzed before and after adjusting the risk factor levels for mothers' and daughters' waist circumferences (WCs) within each group to determine whether risk factor correlations were, in part, a result of the central obesity correlations. After the non-communicable disease risk factor levels of participants were adjusted for their WCs, the mother-daughter correlations remained significant. The consistent association of central obesity between mothers and daughters may indicate the key role that could be played by the mother in the primary prevention of central obesity, particularly in high-risk families.

  5. Macrophage Activation in Pediatric Nonalcoholic Fatty Liver Disease (NAFLD) Correlates with Hepatic Progenitor Cell Response via Wnt3a Pathway

    PubMed Central

    Renzi, Anastasia; De Stefanis, Cristiano; Stronati, Laura; Franchitto, Antonio; Alisi, Anna; Onori, Paolo; De Vito, Rita; Alpini, Gianfranco; Gaudio, Eugenio

    2016-01-01

    Non-alcoholic fatty liver disease is one of the most important causes of liver-related morbidity in children. In non-alcoholic fatty liver disease, the activation of liver resident macrophage pool is a central event in the progression of liver injury. The aims of the present study were to evaluate the polarization of liver macrophages and the possible role of Wnt3a production by macrophages in hepatic progenitor cell response in the progression of pediatric non-alcoholic fatty liver disease. 32 children with biopsy-proven non-alcoholic fatty liver disease were included. 20 out of 32 patients were treated with docosahexaenoic acid for 18 months and biopsies at the baseline and after 18 months were included. Hepatic progenitor cell activation, macrophage subsets and Wnt/β-catenin pathway were evaluated by immunohistochemistry and immunofluorescence. Our results indicated that in pediatric non-alcoholic fatty liver disease, pro-inflammatory macrophages were the predominant subset. Macrophage polarization was correlated with Non-alcoholic fatty liver disease Activity Score, ductular reaction, and portal fibrosis; docosahexaenoic acid treatment determined a macrophage polarization towards an anti-inflammatory phenotype in correlation with the reduction of serum inflammatory cytokines, with increased macrophage apoptosis, and with the up-regulation of macrophage Wnt3a expression; macrophage Wnt3a expression was correlated with β-catenin phosphorylation in hepatic progenitor cells and signs of commitment towards hepatocyte fate. In conclusion, macrophage polarization seems to have a key role in the progression of pediatric non-alcoholic fatty liver disease; the modulation of macrophage polarization could drive hepatic progenitor cell response by Wnt3a production. PMID:27310371

  6. Correlation of conventional and conformational anti-desmoglein antibodies with phenotypes and disease activities in patients with pemphigus vulgaris.

    PubMed

    Li, Zhiliang; Zhang, Jiechen; Xu, Haoxiang; Jin, Peiying; Feng, Suying; Wang, Baoxi

    2015-04-01

    Pemphigus is an autoimmune disease characterised by anti-desmoglein (Dsg) antibodies in the serum of patients. The disease can be divided into pemphigus foliaceus and pemphigus vulgaris. Anti-Dsg1 antibody is generally related to pemphigus with cutaneous lesion, and the anti-Dsg3 antibody is related to pemphigus with mucosa lesion. Twenty-nine patients with pemphigus vulgaris were selected in the clinical study. The severity of the cutaneous and mucosa lesions of these patients was evaluated using Pemphigus disease area index (PDAI). Conventional and conformational anti-Dsg index values were determined using enzyme-linked immunosorbent assay (ELISA) and ethylenediaminetetraacetic acid-treated ELISA. The relationship between clinical phenotypes and immunological profiles was analysed. In the correlation analysis, both the conventional and conformational anti-Dsg1 ELISA index values were correlated with the total and cutaneous PDAIs. In addition, conformational anti-Dsg3 ELISA index values exhibited a positive correlation with cutaneous PDAI in both types of pemphigus vulgaris, whereas no correlation was observed for the conventional anti-Dsg3 ELISA index values.

  7. Correlation of Promis Scales and Clinical Measures Among Chronic Obstructive Pulmonary Disease Patients With and Without Exacerbations

    PubMed Central

    Irwin, Debra E.; Atwood, Charles A.; Hays, Ron D.; Spritzer, Karen; Liu, Honghu; Donohue, James F.; Leidy, Nancy Kline; Yount, Susan E.; DeWalt, Darren A.

    2014-01-01

    Purpose The Patient-Reported Outcomes Measurement Information System (PROMIS®) initiative was developed to advance the methodology of PROs applicable to chronic diseases. Chronic obstructive pulmonary disease (COPD) is a progressive chronic disease associated with poor health. This study was designed to examine the correlation of PROMIS health-related quality of life (HRQOL) scales and clinical measures among COPD patients. Methods A cross-sectional analysis was conducted comparing patients who were stable (n = 100) with those currently experiencing a COPD exacerbation (n=85). All PROMIS measures for adults available at the time of the study (2008), disease-targeted and other HRQOL instruments, health literacy, percent predicted FEV1, and a 6-minute walk distance were assessed when patients were considered clinically stable. Results Stable COPD patients reported significantly (p≤0.05) better health-related quality of life on PROMIS domains than patients experiencing an exacerbation. PROMIS domain scores were significantly (p≤0.01) correlated with each of legacy measures. Six-minute walk scores were most highly correlated with the PROMIS physical function domain scores (r=0.53) followed by the fatigue (r=-0.26), social (r=0.24) and to a lesser extent depression (r=-0.23) and anxiety (r=-0.22) domain scores. Percent predicted FEV1 score was significantly associated with PROMIS physical function scores (r=0.27). Conclusion This study provides support for the validity of the PROMIS measures in COPD patients. PMID:25307510

  8. Correlation between decreased CSF α-synuclein and Aβ₁₋₄₂ in Parkinson disease.

    PubMed

    Buddhala, Chandana; Campbell, Meghan C; Perlmutter, Joel S; Kotzbauer, Paul T

    2015-01-01

    Accumulation of misfolded α-synuclein (α-syn) protein in Lewy bodies and neurites is the cardinal pathologic feature of Parkinson disease (PD), but abnormal deposition of other proteins may also play a role. Cerebrospinal fluid (CSF) levels of proteins known to accumulate in PD may provide insight into disease-associated changes in protein metabolism and their relationship to disease progression. We measured CSF α-syn, amyloid β₁₋₄₂ (Aβ₁₋₄₂), and tau from 77 nondemented PD and 30 control participants. CSF α-syn and Aβ₁₋₄₂ were significantly lower in PD compared with controls. In contrast with increased CSF tau in Alzheimer disease, CSF tau did not significantly differ between PD and controls. CSF protein levels did not significantly correlate with ratings of motor function or performance on neuropsychological testing. As expected, CSF Aβ₁₋₄₂ inversely correlated with [(11)C]-Pittsburgh compound B (PiB) mean cortical binding potential, with PiB(+) PD participants having lower CSF Aβ₁₋₄₂ compared with PiB(-) PD participants. Furthermore, CSF α-syn positively correlated with Aβ₁₋₄₂ in PD participants but not in controls, suggesting a pathophysiologic connection between the metabolisms of these proteins in PD.

  9. Complement effectors, C5a and C3a, in cystic fibrosis lung fluid correlate with disease severity

    PubMed Central

    Hair, Pamela S.; Sass, Laura A.; Vazifedan, Turaj; Shah, Tushar A.; Krishna, Neel K.

    2017-01-01

    In cystic fibrosis (CF), lung damage is mediated by a cycle of obstruction, infection, inflammation and tissue destruction. The complement system is a major mediator of inflammation for many diseases with the effectors C5a and C3a often playing important roles. We have previously shown in a small pilot study that CF sputum soluble fraction concentrations of C5a and C3a were associated with clinical measures of CF disease. Here we report a much larger study of 34 CF subjects providing 169 testable sputum samples allowing longitudinal evaluation comparing C5a and C3a with clinical markers. Levels of the strongly pro-inflammatory C5a correlated negatively with FEV1% predicted (P < 0.001), whereas the often anti-inflammatory C3a correlated positively with FEV1% predicted (P = 0.01). C5a concentrations correlated negatively with BMI percentile (P = 0.017), positively with worsening of an acute pulmonary exacerbation score (P = 0.007) and positively with P. aeruginosa growth in sputum (P = 0.002). C5a levels also correlated positively with concentrations of other sputum markers associated with worse CF lung disease including neutrophil elastase (P < 0.001), myeloperoxidase activity (P = 0.006) and DNA concentration (P < 0.001). In contrast to C5a, C3a levels correlated negatively with worse acute pulmonary exacerbation score and correlated negatively with sputum concentrations of neutrophil elastase, myeloperoxidase activity and DNA concentration. In summary, these data suggest that in CF sputum, increased C5a is associated with increased inflammation and poorer clinical measures, whereas increased C3a appears to be associated with less inflammation and improved clinical measures. PMID:28278205

  10. Perceived stress correlates with disturbed sleep: a link connecting stress and cardiovascular disease.

    PubMed

    Kashani, Mariam; Eliasson, Arn; Vernalis, Marina

    2012-01-01

    The association between stress and cardiovascular disease (CVD) risk is becoming established. A mechanistic link clarifying the intermediate steps between the experience of stress and the development of CVD would support this association. We sought to examine the role of perceived stress as a factor associated with disturbed sleep with the goal of providing an explanation for the stress-CVD connection. We performed a cross-sectional analysis of data recorded by subjects at entry to our CVD prevention program. Data collection included questionnaire surveys, anthropometrics, and a CVD-relevant laboratory panel. Of 350 consecutively enrolled subjects (mean age 54.4 ± 12.4 [SD] years, 138 men, 39%), 165 (47%) scored above the mean for stress measures. These high-stress subjects displayed an increased cardiovascular risk profile including elevated body mass index (mean ± SD 31.1 ± 5.9 vs. 29.0 ± 5.9, r(s) = 0.175), increased waist circumference (102 ± 17 cm vs. 98 ± 14, r(s) = 0.135), and elevated high-sensitivity serum C-reactive protein (0.384 mg/dl vs. 0.356, r(s) = 0.109). High-stress subjects also demonstrated greater daytime sleepiness (Epworth Sleepiness Scale: 10.4 ± 5.0 vs. 7.8 ± 4.8, r(s) < 0.316), greater fatigue (fatigue scale: 5.4 ± 2.2 vs. 3.4 ± 2.4, r(s) = 0.484), poorer sleep quality (Pittsburgh Sleep Quality Index: 8.5 ± 4.4 vs. 5.9 ± 4.0, r(s) = 0.416), and shorter sleep duration (20 min less/24 h, r(s) = negative 0.177) with a higher risk for sleep apnea (60% at high risk vs. 40%, p = 0.003) than low-stress subjects. High stress was associated with significant disturbances in sleep duration and sleep quality. Stress levels also correlated with daytime consequences of disturbed sleep. The stress-sleep connection may be an important mechanistic mediator of the association between stress and CVD.

  11. HIV antibody testing and its correlates among heterosexual attendees of sexually transmitted disease clinics in China

    PubMed Central

    2013-01-01

    Background This study was conducted to determine the prevalence of HIV antibody testing and associated factors among heterosexual sexually transmitted disease (STD) clinic attendees in China. Methods A self-administered questionnaire was administered among 823 attendees of 4 STD clinics of Zhejiang Province, China in October to December 2007. Psychosocial and behavioural factors associated with HIV antibody testing were identified in both genders using univariate and multivariate analyses. Results Of all 823 STD clinic attendees, 9.3% of male and 18.0% of female attendees underwent HIV antibody testing in the most recent 6 months, and 60% of the participants had gotten no educational/behavioral intervention related to HIV prevention. The correlates for HIV antibody testing in the most recent 6 months as identified by multivariate analysis were ever condom use [odds ratio (OR), 10.37; 95% confidence interval (CI), 1.32–81.22]; ever anal/oral sex (OR, 3.13; 95% CI, 1.03–9.50) during their lifetime; having ever received three to seven types of behavioural interventions in the most recent 6 months (OR, 3.70; 95% CI, 1.32–10.36) among male subjects; and ever condom use (OR, 12.50; 95% CI, 2.20–71.01), STD history (OR, 3.86; 95% CI, 1.26–11.86) over their lifetime, or having ever received three to seven types of behavioural interventions in the most recent 6 months (OR, 8.68; 95% CI, 2.39–31.46) in female subjects. A lifetime experience of casual/commercial sex partners was strongly negatively associated with HIV testing in female subjects (OR, 0.08; 95% CI, 0.01–0.83). Conclusion The low prevalence of HIV antibody testing and behavioural intervention among STD clinic attendees indicates a need for more targeted, intensive behavioural interventions to promote HIV antibody testing in this population. PMID:23327359

  12. Nigral Tau pathology and striatal amyloid-β deposition does not correlate with striatal dopamine deficit in Alzheimer's disease.

    PubMed

    Schauer, Tabea H; Lochner, Maximilian; Kovacs, Gabor G

    2012-12-01

    Extrapyramidal symptoms may appear in Alzheimer's disease (AD). In the present study, using morphometric immunohistochemistry in 34 cases with AD-related pathology, we evaluated whether nigral burden of tau pathology or striatal burden of amyloid-β deposition correlates with dopamine transporter (DAT) expression in the striatum. Our observations show a lack of correlation between these variables and support the notion that lower striatal DAT expression in AD patients suggests concomitant nigral α-synuclein pathology. Extrapyramidal symptoms may have a complex background in AD.

  13. Anti-serum amyloid component P antibodies in patients with systemic lupus erythematosus correlate with disease activity

    PubMed Central

    Zandman-Goddard, G; Blank, M; Langevitz, P; Slutsky, L; Pras, M; Levy, Y; Shovman, O; Witte, T; Doria, A; Rovensky, J; Shoenfeld, Y

    2005-01-01

    Objective: To determine the presence of raised titres of anti-serum amyloid P component (SAP) antibodies in patients with systemic lupus erythematosus (SLE) and to evaluate their correlation with clinical disease by the SLEDAI and clinical manifestations. Methods: 452 samples were screened for raised anti-SAP antibody titres by an ELISA. Clinical measures and SLEDAI scores were independently reviewed from medical records. 21 serial samples from 7 patients with SLE were assessed for a change in anti-SAP antibody titres after treatment. Results: Raised anti-SAP antibody titres were detected in 145/328 (44%) SLE samples. In 112 randomly selected samples, 69/112 (62%) patients had raised anti-SAP antibodies and anti-dsDNA antibody titres, whereas only 32/112 (28%) had raised anti-dsDNA antibody titres without raised anti-SAP antibody titres. The mean titre of anti-SAP antibodies in patients with active disease was higher than in patients with inactive disease and controls. SLEDAI scores, assessed in 54 patients, were raised in 26/31 (84%) patients with raised anti-SAP antibody titres. A SLEDAI score ⩾8 was found in 16/31 (52%) patients with raised anti-SAP antibody titres but in only 5/23 (22%) patients without raised titres. No specific pattern of disease was detected in patients with or without raised titres of anti-SAP antibodies. Serial sampling from patients with active SLE and raised anti-SAP antibody titres showed that anti-SAP antibody titres decreased after treatment and correlated with clinical improvement. Conclusion: Raised anti-SAP antibody titres detected in patients with SLE correlate with disease activity and decrease with improvement of clinical disease, and thus may serve as an additional prognostic marker. PMID:16014675

  14. Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer's and Parkinson's diseases correlate with disease status and features of pathology.

    PubMed

    Burgos, Kasandra; Malenica, Ivana; Metpally, Raghu; Courtright, Amanda; Rakela, Benjamin; Beach, Thomas; Shill, Holly; Adler, Charles; Sabbagh, Marwan; Villa, Stephen; Tembe, Waibhav; Craig, David; Van Keuren-Jensen, Kendall

    2014-01-01

    The discovery and reliable detection of markers for neurodegenerative diseases have been complicated by the inaccessibility of the diseased tissue--such as the inability to biopsy or test tissue from the central nervous system directly. RNAs originating from hard to access tissues, such as neurons within the brain and spinal cord, have the potential to get to the periphery where they can be detected non-invasively. The formation and extracellular release of microvesicles and RNA binding proteins have been found to carry RNA from cells of the central nervous system to the periphery and protect the RNA from degradation. Extracellular miRNAs detectable in peripheral circulation can provide information about cellular changes associated with human health and disease. In order to associate miRNA signals present in cell-free peripheral biofluids with neurodegenerative disease status of patients with Alzheimer's and Parkinson's diseases, we assessed the miRNA content in cerebrospinal fluid and serum from postmortem subjects with full neuropathology evaluations. We profiled the miRNA content from 69 patients with Alzheimer's disease, 67 with Parkinson's disease and 78 neurologically normal controls using next generation small RNA sequencing (NGS). We report the average abundance of each detected miRNA in cerebrospinal fluid and in serum and describe 13 novel miRNAs that were identified. We correlated changes in miRNA expression with aspects of disease severity such as Braak stage, dementia status, plaque and tangle densities, and the presence and severity of Lewy body pathology. Many of the differentially expressed miRNAs detected in peripheral cell-free cerebrospinal fluid and serum were previously reported in the literature to be deregulated in brain tissue from patients with neurodegenerative disease. These data indicate that extracellular miRNAs detectable in the cerebrospinal fluid and serum are reflective of cell-based changes in pathology and can be used to assess

  15. Correlation of spicule sign on computed tomography scans with peripheral lung cancers associated with interstitial lung disease and chronic obstructive pulmonary disease.

    PubMed

    Chen, L; Gao, L; Wu, W L

    2015-03-27

    The objective of this study was to investigate the correlation between spicular signs on computed tomography (CT) scans and peripheral lung cancer (PLC) that is associated with interstitial lung disease (ILD) and chronic obstructive pulmonary disease (COPD). We analyzed clinical data from 96 PLC cases and grouped patients based on whether they had interstitial pneumonia into either ILD/COPD group or non-ILD/COPD group. The occurrence rate of spicule sign was 90.3% in the ILD/COPD group and 61.8% in the non-ILD/COPD group, respectively. There was a significant difference between these groups (P < 0.05). There were no significant differences in the occurrence rate of spicular signs among patients with different pathological types of PLC. The severity of ILD affected the spicular morphology on CT scans directly. There was a significant correlation between the appearance of spicule sign on CT scans and PLC that was associated with ILD/COPD.

  16. Blood-Borne Activity-Dependent Neuroprotective Protein (ADNP) is Correlated with Premorbid Intelligence, Clinical Stage, and Alzheimer's Disease Biomarkers.

    PubMed

    Malishkevich, Anna; Marshall, Gad A; Schultz, Aaron P; Sperling, Reisa A; Aharon-Peretz, Judith; Gozes, Illana

    2016-01-01

    Biomarkers for Alzheimer's disease (AD) are vital for disease detection in the clinical setting. Discovered in our laboratory, activity-dependent neuroprotective protein (ADNP) is essential for brain formation and linked to cognitive functions. Here, we revealed that blood borne expression of ADNP and its paralog ADNP2 is correlated with premorbid intelligence, AD pathology, and clinical stage. Age adjustment showed significant associations between: 1) higher premorbid intelligence and greater serum ADNP, and 2) greater cortical amyloid and lower ADNP and ADNP2 mRNAs. Significant increases in ADNP mRNA levels were observed in patients ranging from mild cognitive impairment (MCI) to AD dementia. ADNP2 transcripts showed high correlation with ADNP transcripts, especially in AD dementia lymphocytes. ADNP plasma/serum and lymphocyte mRNA levels discriminated well between cognitively normal elderly, MCI, and AD dementia participants. Measuring ADNP blood-borne levels could bring us a step closer to effectively screening and tracking AD.

  17. Medicare Expenditure Correlates of Atrophy and Cerebrovascular Disease in Older Adults.

    PubMed

    Last, Briana S; García Rubio, Maria-José; Zhu, Carolyn W; Cosentino, Stephanie; Manly, Jennifer J; DeCarli, Charles; Stern, Yaakov; Brickman, Adam M

    2017-01-01

    Background/Study Context: Magnetic resonance imaging (MRI) markers of cerebrovascular disease and atrophy are common in older adults and are associated with cognitive and medical burden. However, the extent to which they are related to health care expenditures has not been examined. We studied whether increased Medicare expenditures were associated with brain markers of atrophy and cerebrovascular disease in older adults.

  18. Diagnosis of Sanfilippo disease correlating clinical, radiological and biochemical findings-a case report.

    PubMed

    Agrawal, Udit; Meshram, Ajay; Vagha, Jayant; Swarnkar, Kirti; Palandurkar, Kamlesh

    2012-10-01

    Mucopolysaccharidoses (MPS) are a group of genetic diseases and its diagnosis is a challenging task due to multiple differential diagnosis. We had combined clinical findings, radiological and ophthalmological features. Biochemical test for urine glycosaminoglycans (GAG) was done for confirmation of diagnosis in the patient. The case of Sanfilippo disease was characterized by slowly progressive, severe CNS involvement with mild somatic disease. Radiological features were suggestive of Sanfilippo disease and urine GAG test for MPS was positive in the case. With the clinical features we had multiple differential diagnoses. The radiological investigations minimized the list and the biochemical test confirmed GAG in urine. In this case the combination of clinical, radiological and biochemical findings confirmed the diagnosis of Sanfilippo disease.

  19. Examining the neural correlates of depressive and motor symptoms in Parkinson's disease using Frequency Component Analysis (FCA)

    NASA Astrophysics Data System (ADS)

    Song, Xiaopeng; Hu, Xiao; Zhou, Shuqin; Liu, Weiguo; Liu, Yijun; Zhu, Huaiqiu; Gao, Jia-Hong

    2016-03-01

    Depression is prevalent among patients with Parkinson's disease (PD); however the pathophysiology of depression in PD is not well understood. In order to investigate how depression and motor impairments differentially and interactively affect specific brain regions in Parkinson's disease, we introduced a new data driven approach, namely Frequency Component Analysis (FCA), to decompose the resting-state functional magnetic resonance imaging data of 59 subjects with Parkinson's disease into different frequency bands. We then evaluated the main effects of motor severity and depression, and their interactive effects on the BOLD-fMRI signal oscillation energy in these specific frequency components. Our results show that the severity of motor symptoms is more negatively correlated with energy in the frequency band of 0.10-0.25Hz in the bilateral thalamus (THA), but more positively correlated with energy in the frequency band of 0.01-0.027Hz in the bilateral postcentral gyrus (PoCG). In contrast, the severity of depressive symptoms is more associated with the higher energy of the high frequency oscillations (>0.1Hz) but lower energy of 0.01-0.027Hz in the bilateral subgenual gyrus (SGC). Importantly, the interaction between motor and depressive symptoms is negatively correlated with the energy of high frequency oscillations (>0.1Hz) in the substantia nigra/ventral tegmental area (SN/VTA), left hippocampus (HIPP), left inferior orbital frontal cortex (OFC), and left temporoparietal junction (TPJ), but positively correlated with the energy of 0.02-0.05Hz in the left inferior OFC, left TPJ, left inferior temporal gyrus (ITG), and bilateral cerebellum. These results demonstrated that FCA was a promising method in interrogating the neurophysiological implications of different brain rhythms. Our findings further revealed the neural bases underlying the interactions as well the dissociations between motor and depressive symptoms in Parkinson's disease.

  20. A molecular marker of disease activity in autoimmune liver diseases with histopathological correlation; FoXp3/RORγt ratio.

    PubMed

    Mitra, Suvradeep; Anand, Shashi; Das, Ashim; Thapa, Baburam; Chawla, Yogesh Kumar; Minz, Ranjana Walker

    2015-11-01

    Autoimmune liver diseases (AILDs) encompass a group of diseases with variable clinicopathological manifestations. Th17 and Treg cells have roles in the pathogenesis of AILDs with a balance shifted towards a relative increase in activity of the Th17 cells. In this study, the balance between the transcription factors of Treg and Th17 cells (FoXp3 and RORγt) was sought as a molecular marker of disease activity and to highlight the pathogenesis. The peripheral blood samples of 46 treatment-naive patients were collected and RNA was extracted. Real time PCR was performed and the ratio of gene expression was calculated. Histopathology of 18 patients was obtained and the activity score of these biopsies were also corroborated with their respective molecular (FoXp3/RORγt) (FRGT=FoXp3-ROR Gamma T) ratio. The FRGT ratio in healthy individuals was close to 1 and in disease the ratio changed significantly. This ratio (FRGT) was not significantly different in different varieties of AILD or in adult or paediatric form of the disease. However, the ratio remained consistently below 1 (mean 0.3) in acute disease and high (mean 224.7) in chronic or asymptomatic form of the disease (p < 0.001). The histopathological activity score also significantly correlated with the ratio. This signified the relative excess of Th17 (RORγt) in active disease as compared to Treg (FoXp3) and the reverse in chronic form. This ratio can be an important peripheral molecular marker to assess the disease activity without the necessity of performing a liver biopsy.

  1. An Evil Backstage Manipulator: Psychological Factors Correlated with Health-Related Quality of Life in Chinese Patients with Crohn's Disease

    PubMed Central

    Liu, Song; Hong, Zhiwu; Li, Xiaoting; Yao, Min; Yan, Dongsheng; Ren, Huajian; Wu, Xiuwen; Wang, Gefei; Gu, Guosheng; Xia, Qiuyuan; Han, Gang; Li, Jieshou

    2013-01-01

    Health-related quality of life (HRQoL) is recommended as one of essential parameters to evaluate treatment effect and clinical outcome in patients with Crohn's disease (CD). Recent studies reported that psychological factors might play a role in HRQoL in Western and American CD patients. Sufficient evidences in Chinese CD patients are still unavailable. This study is dedicated to investigate the correlation of various psychological factors with HRQoL in Chinese CD patients. We prospectively collected 40 active and 40 quiescent CD patients in China and found that psychological factors, especially neuroticism and anxiety, significantly correlate with and affect HRQoL in both active and quiescent CD groups. This is the first report revealing correlation between psychological factors and HRQoL in Chinese CD patients. Therefore, we assume that our results can contribute to a better understanding of etiology and tailoring of management in Chinese patients with Crohn's disease and are beneficial to our colleagues to compare the heterogeneous characteristics of Crohn's disease in different ethnic groups. PMID:24453858

  2. Dephosphorylation of circulating human Osteopontin correlates with severe valvular calcification in patients with Calcific Aortic Valve Disease

    PubMed Central

    Sainger, Rachana; Grau, Juan B.; Poggio, Paolo; Branchetti, Emanuela; Bavaria, Joseph E.; Gorman, Joseph H.; Gorman, Robert C.; Ferrari, Giovanni

    2011-01-01

    Context Calcific Aortic Valve Disease (CAVD) is an active pathological process leading to biomineralization of the aortic cusps. We characterized circulating and tissue Osteopontin (OPN) as a biomarker for CAVD. Objectives Here we investigate the post-translational modifications of circulating OPN and correlate the phosphorylation status with the ability to prevent calcification. Methods Circulating OPN levels were estimated in CAVD patients (n=51) and controls (n=56). In a subgroup of 27 subjects, OPN was purified and the phosphorylation status analyzed. Results Plasma OPN levels were significantly elevated in CAVD patients as compared to the controls and correlates with the aortic valve calcium score. Our study demonstrates that phospho-threonine levels of OPN purified from controls were higher when compared to CAVD subjects, while phosphoserine and phospho-tyrosine levels were comparable between the two groups. Conclusion The dephosphorylation of circulating OPN correlates with severe valvular calcification in patients with CAVD. PMID:22191734

  3. VENTRICULAR MAPS IN 804 SUBJECTS CORRELATE WITH COGNITIVE DECLINE, CSF PATHOLOGY, AND IMMINENT ALZHEIMER’S DISEASE

    PubMed Central

    Chou, Yi-Yu; Leporé, Natasha; Madsen, Sarah K.; Saharan, Priya; Hua, Xue; Jack, Clifford R.; Shaw, Leslie M.; Trojanowski, John Q.; Weiner, Michael W.; Toga, Arthur W.; Thompson, Paul M.

    2017-01-01

    There is an urgent need for neuroimaging biomarkers of Alzheimer’s disease (AD) that correlate with cognitive decline, and with accepted measures of pathology detectable in cerebrospinal fluid (CSF). Ideal biomarkers should also be able to predict future decline, and should be computable automatically from hundreds to thousands of images without user intervention. Here we used our multi-atlas fluid image alignment method (MAFIA [1]), to automatically segment parametric 3D surface models of the lateral ventricles in brain MRI scans from 184 AD, 391 MCI, and 229 healthy elderly controls. Radial expansion of the ventricles, computed pointwise, was correlated with measures of (1) clinical decline, (2) pathology from CSF, and (3) future deterioration. Surface–based correlation maps were assessed using a cumulative distribution function method to rank influential covariates according to their effect sizes. The resulting approach is highly automated, and boosts the power of fluid image registration by integrating multiple independent registrations to reduce segmentation errors.

  4. Serum levels of autoantibodies against monomeric C-reactive protein are correlated with disease activity in systemic lupus erythematosus

    PubMed Central

    Sjöwall, Christopher; Bengtsson, Anders A; Sturfelt, Gunnar; Skogh, Thomas

    2004-01-01

    This study was performed to investigate the relation between IgG autoantibodies against human C-reactive protein (anti-CRP) and disease activity measures in serial serum samples from 10 patients with systemic lupus erythematosus (SLE), of whom four had active kidney involvement during the study period. The presence of anti-CRP was analysed by enzyme-linked immunosorbent assay. The cut-off for positive anti-CRP test was set at the 95th centile of 100 healthy blood donor sera. Specificity of the anti-CRP antibody binding was evaluated by preincubating patient sera with either native or monomeric CRP. Disease activity was determined by the SLE disease activity index (SLEDAI), serum levels of CRP, anti-DNA antibodies, complement components and blood cell counts. Of 50 serum samples, 20 (40%) contained antibodies reactive with monomeric CRP, and 7 of 10 patients were positive on at least one occasion during the study. All patients with active lupus nephritis were positive for anti-CRP at flare. Frequent correlations between anti-CRP levels and disease activity measures were observed in anti-CRP-positive individuals. Accumulated anti-CRP data from all patients were positively correlated with SLEDAI scores and anti-DNA antibody levels, whereas significant inverse relationships were noted for complement factors C1q, C3 and C4, and for lymphocyte counts. This study confirms the high prevalence of anti-CRP autoantibodies in SLE and that the antibody levels are correlated with clinical and laboratory disease activity measures. This indicates that anti-CRP antibodies might have biological functions of pathogenetic interest in SLE. Further prospective clinical studies and experimental studies on effects mediated by anti-CRP antibodies are warranted. PMID:15059271

  5. Auditory- and Vestibular-Evoked Potentials Correlate with Motor and Non-Motor Features of Parkinson’s Disease

    PubMed Central

    Shalash, Ali Soliman; Hassan, Dalia Mohamed; Elrassas, Hanan Hani; Salama, Mohamed Mosaad; Méndez-Hernández, Edna; Salas-Pacheco, José M.; Arias-Carrión, Oscar

    2017-01-01

    Degeneration of several brainstem nuclei has been long related to motor and non-motor symptoms (NMSs) of Parkinson’s disease (PD). Nevertheless, due to technical issues, there are only a few studies that correlate that association. Brainstem auditory-evoked potential (BAEP) and vestibular-evoked myogenic potential (VEMP) responses represent a valuable tool for brainstem assessment. Here, we investigated the abnormalities of BAEPs, ocular VEMPs (oVEMPs), and cervical VEMPs (cVEMPs) in patients with PD and its correlation to the motor and NMSs. Fifteen patients diagnosed as idiopathic PD were evaluated by Unified Parkinson’s Disease Rating Scale and its subscores, Hoehn and Yahr scale, Schwab and England scale, and Non-Motor Symptoms Scale. PD patients underwent pure-tone, speech audiometry, tympanometry, BAEP, oVEMPs, and cVEMPs, and compared to 15 age-matched control subjects. PD subjects showed abnormal BAEP wave morphology, prolonged absolute latencies of wave V and I–V interpeak latencies. Absent responses were the marked abnormality seen in oVEMP. Prolonged latencies with reduced amplitudes were seen in cVEMP responses. Rigidity and bradykinesia were correlated to the BAEP and cVEMP responses contralateral to the clinically more affected side. Contralateral and ipsilateral cVEMPs were significantly correlated to sleep (p = 0.03 and 0.001), perception (p = 0.03), memory/cognition (p = 0.025), and urinary scores (p = 0.03). The oVEMP responses showed significant correlations to cardiovascular (p = 0.01) and sexual dysfunctions (p = 0.013). PD is associated with BAEP and VEMP abnormalities that are correlated to the motor and some non-motor clinical characteristics. These abnormalities could be considered as potential electrophysiological biomarkers for brainstem dysfunction and its associated motor and non-motor features. PMID:28289399

  6. Auditory- and Vestibular-Evoked Potentials Correlate with Motor and Non-Motor Features of Parkinson's Disease.

    PubMed

    Shalash, Ali Soliman; Hassan, Dalia Mohamed; Elrassas, Hanan Hani; Salama, Mohamed Mosaad; Méndez-Hernández, Edna; Salas-Pacheco, José M; Arias-Carrión, Oscar

    2017-01-01

    Degeneration of several brainstem nuclei has been long related to motor and non-motor symptoms (NMSs) of Parkinson's disease (PD). Nevertheless, due to technical issues, there are only a few studies that correlate that association. Brainstem auditory-evoked potential (BAEP) and vestibular-evoked myogenic potential (VEMP) responses represent a valuable tool for brainstem assessment. Here, we investigated the abnormalities of BAEPs, ocular VEMPs (oVEMPs), and cervical VEMPs (cVEMPs) in patients with PD and its correlation to the motor and NMSs. Fifteen patients diagnosed as idiopathic PD were evaluated by Unified Parkinson's Disease Rating Scale and its subscores, Hoehn and Yahr scale, Schwab and England scale, and Non-Motor Symptoms Scale. PD patients underwent pure-tone, speech audiometry, tympanometry, BAEP, oVEMPs, and cVEMPs, and compared to 15 age-matched control subjects. PD subjects showed abnormal BAEP wave morphology, prolonged absolute latencies of wave V and I-V interpeak latencies. Absent responses were the marked abnormality seen in oVEMP. Prolonged latencies with reduced amplitudes were seen in cVEMP responses. Rigidity and bradykinesia were correlated to the BAEP and cVEMP responses contralateral to the clinically more affected side. Contralateral and ipsilateral cVEMPs were significantly correlated to sleep (p = 0.03 and 0.001), perception (p = 0.03), memory/cognition (p = 0.025), and urinary scores (p = 0.03). The oVEMP responses showed significant correlations to cardiovascular (p = 0.01) and sexual dysfunctions (p = 0.013). PD is associated with BAEP and VEMP abnormalities that are correlated to the motor and some non-motor clinical characteristics. These abnormalities could be considered as potential electrophysiological biomarkers for brainstem dysfunction and its associated motor and non-motor features.

  7. Neural correlates of adaptive working memory training in a glycogen storage disease type-IV patient.

    PubMed

    Lee, Kristin; Ernst, Thomas; Løhaugen, Gro; Zhang, Xin; Chang, Linda

    2017-03-01

    Glycogen storage disease type-IV has varied clinical presentations and subtypes. We evaluated a 38-year-old man with memory complaints, common symptoms in adult polyglucosan body disease subtype, and investigated cognitive and functional MRI changes associated with two 25-sessions of adaptive working memory training. He showed improved trained and nontrained working memory up to 6-months after the training sessions. On functional MRI, he showed increased cortical activation 1-3 months after training, but both increased and decreased activation 6-months later. Working memory training appears to be beneficial to patients with adult polyglucosan body disease, although continued training may be required to maintain improvements.

  8. Herpes zoster correlates with increased risk of Parkinson's disease in older people: A population-based cohort study in Taiwan.

    PubMed

    Lai, Shih-Wei; Lin, Chih-Hsueh; Lin, Hsien-Feng; Lin, Cheng-Li; Lin, Cheng-Chieh; Liao, Kuan-Fu

    2017-02-01

    Little is known on the relationship between herpes zoster and Parkinson's disease in older people. This study aimed to explore whether herpes zoster could be associated with Parkinson's disease in older people in Taiwan.We conducted a retrospective cohort study using the claim data of the Taiwan National Health Insurance Program. There were 10,296 subjects aged 65 years and older with newly diagnosed herpes zoster as the herpes zoster group and 39,405 randomly selected subjects aged 65 years and older without a diagnosis of herpes zoster as the nonherpes zoster group from 1998 to 2010. Both groups were followed up until subjects received a diagnosis of Parkinson's disease. This follow-up design would explore whether subjects with herpes zoster were at an increased risk of Parkinson's disease. Relative risks were estimated by adjusted hazard ratio (HR) and 95% confidence interval (CI) using the multivariable Cox proportional hazards regression model.The incidence of Parkinson's disease was higher in the herpes zoster group than that in the nonherpes zoster group (4.86 vs 4.00 per 1000 person-years, 95% CI 1.14, 1.29). After adjustment for confounding factors, the multivariable Cox proportional hazards regression model revealed that the adjusted HR of Parkinson's disease was 1.17 for the herpes zoster group (95% CI 1.10, 1.25), compared with the nonherpes zoster group.Older people with herpes zoster confer a slightly increased hazard of developing Parkinson's disease when compared to those without herpes zoster. We think that herpes zoster correlates with increased risk of Parkinson's disease in older people. When older people with herpes zoster seek help, clinicians should pay more attention to the development of the cardinal symptoms of Parkinson's disease.

  9. Arylsulfatase a gene polymorphisms in relapsing remitting multiple sclerosis: genotype-phenotype correlation and estimation of disease progression.

    PubMed

    Baronica, Koraljka Bacić; Mlinac, Kristina; Ozretić, David; Vladić, Anton; Bognar, Svjetlana Kalanj

    2011-01-01

    Arylsulfatase A (ASA) is a lysosomal enzyme involved in catabolism of cerebroside-sulfate, major lipid constituent of oligodendrocyte membranes. Various polymorphisms in ASA gene have been described, leading to different levels of enzyme deficiency. Progressive demyelination occurs in metachromatic leukodystrophy (MLD), while the condition of ASA-pseudodeficiency (ASA-PD) is suggested to contribute to complex pathogenesis of multiple sclerosis (MS). This work presents usefulness of genotype-phenotype correlation in estimation of disease severity and progression. The presence of two most common mutations associated with ASA-PD was analyzed in 56 patients with diagnosis of relapsing-remitting multiple sclerosis, by polymerase chain reaction restriction fragment length polymorphism method. In MS patients confirmed as ASA-PD mutations carriers, arylsulfatase activity was determined in leukocyte homogenates by spectrophotometry. To determine whether there is a difference between disability level and/or disease progression in patients with or without mutations we have estimated disability level using Expanded disability status scale (EDSS) and disease progression using Multiple sclerosis severity score (MSSS). Correlation of genotypes and disease progression was statistically analyzed by Kruskal-Wallis test. Patients showing higher MSSS score and found to be carriers of both analyzed ASA-PD mutations were additionally examined using conventional magnetic resonance (MR) techniques. The presence of either one or both mutations was determined in 13 patients. Lower ASA activities were observed in all MS patients carrying the mutations. Nine of the mutations carriers had mild disability (EDSS=0-4.0), 1 had moderate disability (EDSS=4.5-5.5), and 3 had severe disability (EDSS > or = 6.0). On the other hand, only 3 MS patients who were mutation carriers showed MSSS values lower than 5.000 while in other MS patients-mutation carriers the MSSS values ranged from 5.267 to 9

  10. Antibodies to chondroitin sulfates A, B, and C: clinico-pathological correlates in neurological diseases.

    PubMed

    Briani, C; Santoro, M; Latov, N

    2000-08-01

    Anti-chondroitin sulfates (ChSs) antibodies have been reported in neuropathy and neurodegenerative diseases. Differences in specificities may account for their association with different diseases. Sera from 303 neurological patients were tested for antibodies to ChSs A, B, C. Titers >/=51,200 were found in 16 patients (eight peripheral neuropathy, three motor neuron disease, four multiple sclerosis, one myelitis). Three patients also had anti-sulfatides antibodies, which in two cases cross-reacted with ChSs. By indirect immunofluorescence, positive sera stained nuclei on normal human peripheral nerve sections. These findings indicate that human anti-ChSs antibodies are broadly reactive and not specific to any neurological disease.

  11. Thermal conductivity of biological cells at cellular level and correlation with disease state

    NASA Astrophysics Data System (ADS)

    Park, Byoung Kyoo; Woo, Yunho; Jeong, Dayeong; Park, Jaesung; Choi, Tae-Youl; Simmons, Denise Perry; Ha, Jeonghong; Kim, Dongsik

    2016-06-01

    This paper reports the thermal conductivity k of matched pair cell lines: two pairs of a normal and a cancer cell, one pair of a primary and metastatic cell. The 3ω method with a nanoscale thermal sensor was used to measure k at the single-cell level. To observe the difference in k between normal and cancer cells, the measurements were conducted for Hs 578Bst/Hs 578 T (human breast cells) and TE 353.Sk/TE 354.T (human skin cells). Then k of WM-115/WM-266-4, a primary and metastatic pair of human skin cell, was measured to find the effect of disease progression on k. The measured k data for normal and disease cell samples show statistically meaningful differences. In all cases, k decreased as the disease progressed. This work shows that thermal-analysis schemes, such as the 3ω method, have a potential to detect diseases at the cell level.

  12. [Coronary disease. II. Analysis of diastolic pressure-volume correlations and left ventricular elasticity in 110 patients].

    PubMed

    Strauer, B E; Bolte, H D; Heimburg, P; Riecker, G

    1975-04-01

    Left ventricular pressure-volume relationships as well as diastolic compliance were determined in 110 patients with coronary heart disease during routine right and left heart catheterization, coronary angiography and ventriculography. 1. Enddiastolic and endystolic volume of the left ventricle were increased in severe coronary heart disease dependent on the degree of coronary stenosis; left ventricular ejection fraction was consecutively reduced. 2. Left ventricular enddiastolic pressure, diastolic pressure difference and diastolic rate of pressure rise were increased in corrleation with coronary artery stenosis. In contrast, last diastolic volume inflow into the left ventricle was nearly the same in all groups. Left ventricular stiffness, expressed as dP/dV, was significantly increased dependent on the severity degree of coronary artery disease. 3. Diastolic pressure-volume relationships revealed greater steepness in coronary artery disease, significantly dependent, on the corresponding severity degree. 4. Hemodynamic measures (stroke volume, cardiac index, ejection fraction) were decreased parallel to the increased left ventricular wall stiffness. The results demonstrated decreased left ventricular compliance in coronary heart disease. There was a striking correlation between the severity degree of coronary heart disease and the decrease of left ventricular compliance. Validity and limitations of the techniques of estimating left ventricular compliance from diastolic pressures and volumes as well as the effects of a decrease of left ventricular compliance on cardiac mechanics are discussed.

  13. [Correlation between clinical parameters and quantitative analysis of inflammatory infiltrate. Importance in the diagnosis of active periodontal disease].

    PubMed

    Mendieta Fiter, C

    1989-05-01

    Recent studies have indicated that the destruction in chronic periodontal disease occurs in relatively short periods of time which are followed of prolonged periods of inactivity. These bursts of activity are characterized by an increase in the inflammatory reaction. It has been the purpose of this paper to study the correlation between the clinical measurements of periodontal disease and the histomorphometric quantification of areas of dense inflammatory infiltrate. The results of this study show that the clinical parameters that measure gingival inflammation or loss of periodontal attachment are useful to distinguish pathology from normal (p less than 0.003), but lack sensitivity to detect burst of periodontal disease activity (p greater than 0.05).

  14. Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Correlation of Histopathology and MRI in Prion Disease.

    PubMed

    Mente, Karin P; O'Donnell, James K; Jones, Stephen E; Cohen, Mark L; Thompson, Nicolas R; Bizzi, Alberto; Gambetti, Pierluigi; Safar, Jiri G; Appleby, Brian S

    2017-01-01

    Creutzfeldt-Jakob disease (CJD) and other prion diseases are rapidly progressive spongiform encephalopathies that are invariably fatal. Clinical features and magnetic resonance imaging, electroencephalogram, and cerebrospinal fluid abnormalities may suggest prion disease, but a definitive diagnosis can only be made by means of neuropathologic examination. Fluorodeoxyglucose positron emission tomography (FDG-PET) is not routinely used to evaluate patients with suspected prion disease. This study includes 11 cases of definite prion disease in which FDG-PET scans were obtained. There were 8 sporadic CJD cases, 2 genetic CJD cases, and 1 fatal familial insomnia case. Automated FDG-PET analysis revealed parietal region hypometabolism in all cases. Surprisingly, limbic and mesolimbic hypermetabolism were also present in the majority of cases. When FDG-PET hypometabolism was compared with neuropathologic changes (neuronal loss, astrocytosis, spongiosis), hypometabolism was predictive of neuropathology in 80.6% of cortical regions versus 17.6% of subcortical regions. The odds of neuropathologic changes were 2.1 times higher in cortical regions than subcortical regions (P=0.0265). A similar discordance between cortical and subcortical regions was observed between FDG-PET hypometabolism and magnetic resonance imaging diffusion weighted imaging hyperintensity. This study shows that there may be a relationship between FDG-PET hypometabolism and neuropathology in cortical regions in prion disease but it is unlikely to be helpful for diagnosis.

  15. Changes in cholesterol level correlate with the course of pulmonary nontuberculous mycobacterial disease

    PubMed Central

    Hong, Ji Young; Yang, Go Eun; Ko, Yousang; Park, Yong Bum; Sim, Yun Su; Park, Sung Hoon; Lee, Chang Youl; Jung, Ki-Suck

    2016-01-01

    Background Nutritional assessment is important in patients with pulmonary nontuberculous mycobacterial (PNTM) disease. The therapeutic effect of a cholesterol-rich diet in tuberculosis (TB) patients has been demonstrated, but the role of cholesterol in PNTM disease is unclear. This study evaluated the sequential changes in nutritional markers, including cholesterol, total lymphocyte count and visceral fat volume, according to the PNTM disease course. Methods This was an age-, sex- and number of comorbid diseases-matched case-control analysis of 89 patients with PNTM disease and 356 controls, who were participants in a Korean national survey. Results The median body mass index (BMI) and cholesterol level in the PNTM group [BMI =19.7 kg/m2; interquartile range (IQR): 17.8–21.6; cholesterol: 159 mg/dL; IQR, 135–185] were lower than those in controls (BMI: 23.1 kg/m2; IQR, 21.3–25.3; cholesterol: 188 mg/dL; IQR, 164-217; both P<0.001). In a multivariate analysis, Age more than 70 years (OR =3.38; 95% CI: 1.13–10.15, P=0.029), BMI <19.5 kg/m2 (OR =5.09; 95% CI: 1.67–15.48; P=0.004) and cavitary lesions (OR: 3.86; 95% CI: 1.30–11.47; P=0.015) were independently associated with extensive pulmonary lesions involving more than four lobes. The total cholesterol level, total lymphocyte count showed a tendency to decrease in PNTM patients with disease progression (both, P value <0.05), but not in those with a stable disease course. A decrease in cholesterol concentration of >20 mg/dL and a decrease in lymphocyte count more than 200/µL were predictive factors for disease progression (cholesterol: OR =10.50, 95% CI: 2.51–43.98, P=0.001; lymphocyte count: OR =5.32, 95% CI: 1.46–19.35, P=0.011). Conclusions These findings suggest that the change in cholesterol level may be a marker of disease progression in patients with PNTM disease. PMID:27867565

  16. Movement disorder society unified Parkinson disease rating scale experiences in daily living: longitudinal changes and correlation with other assessments.

    PubMed

    Lang, Anthony E; Eberly, Shirley; Goetz, Christopher G; Stebbins, Glenn; Oakes, David; Marek, Ken; Ravina, Bernard; Tanner, Caroline M; Shoulson, Ira

    2013-12-01

    The Movement Disorder Society (MDS) commissioned a revision of the UPDRS with the goals of improving instructions and definitions, more accurately evaluating milder features, and assessing patient-reported outcomes and nonmotor features. To date, no study has evaluated longitudinal changes in components of the MDS-UPDRS over time or correlated these with changes in other scales of various symptoms. We assessed Parts I and II of the MDS-UPDRS (non-Motor and Motor Experiences of Daily Living [nM-EDL, M-EDL]) as well as a number of other scales of motor, cognitive and behavioral function in a large population of patients (n = 383) with early- to mid-stage Parkinson's disease (PD) who had previously participated in a trial of a putative disease-modifying agent. Both parts of a MDS-UPDRS showed significant change over the 3-year follow-up period, with M-EDL scores declining to a greater extent than nM-EDL. Both the scores and their changes over time correlated relatively well with other rating scales of similar disease aspects. Modest correlations with the original version of the UPDRS supported the increased attention to nonmotor symptoms as well as milder levels of severity in the MDS-UPDRS. The M-EDL was much more sensitive to change over time in these early- to mid-stage patients than the original UPDRS Activities of Daily Living (ADL) scale. Finally, we showed no change over time in a small group of individuals with dopamine transporter single-photon emission computed tomography scans without evidence for dopamine deficiency. The nM-EDL and M-EDL components of the MDS-UPDRS provide an effective, relevant measure of change in the broad spectrum of symptoms of PD over the first decade of the disease.

  17. Pathologic and Radiologic Correlation of Adult Cystic Lung Disease: A Comprehensive Review

    PubMed Central

    Parimi, Vamsi; Taddonio, Michale; Kane, Joshua Robert; Yeldandi, Anjana

    2017-01-01

    The presence of pulmonary parenchymal cysts on computed tomography (CT) imaging presents a significant diagnostic challenge. The diverse range of possible etiologies can usually be differentiated based on the clinical setting and radiologic features. In fact, the advent of high-resolution CT has facilitated making a diagnosis solely on analysis of CT image patterns, thus averting the need for a biopsy. While it is possible to make a fairly specific diagnosis during early stages of disease evolution by its characteristic radiological presentation, distinct features may progress to temporally converge into relatively nonspecific radiologic presentations sometimes necessitating histological examination to make a diagnosis. The aim of this review study is to provide both the pathologist and the radiologist with an overview of the diseases most commonly associated with cystic lung lesions primarily in adults by illustration and description of pathologic and radiologic features of each entity. Brief descriptions and characteristic radiologic features of the various disease entities are included and illustrative examples are provided for the common majority of them. In this article, we also classify pulmonary cystic disease with an emphasis on the pathophysiology behind cyst formation in an attempt to elucidate the characteristics of similar cystic appearances seen in various disease entities. PMID:28270943

  18. Paget disease of the breast: mammographic, US, and MR imaging findings with pathologic correlation.

    PubMed

    Lim, Hyo Soon; Jeong, Su Jin; Lee, Ji Shin; Park, Min Ho; Kim, Jin Woong; Shin, Sang Soo; Park, Jin Gyoon; Kang, Heoung Keun

    2011-01-01

    Paget disease is a rare malignancy of the breast characterized by infiltration of the nipple epidermis by adenocarcinoma cells. The clinical features of Paget disease are characteristic and should increase the likelihood of the diagnosis being made. An important point is that more than 90% of cases of Paget disease are associated with an additional underlying breast malignancy. Paget disease is frequently associated with ductal carcinoma in situ (DCIS) in the underlying lactiferous ducts of the nipple-areolar complex; it may even be associated with DCIS or invasive breast cancer elsewhere in the breast, at least 2 cm from the nipple-areolar complex. Nevertheless, mammographic findings may be negative in up to 50% of cases. Magnetic resonance (MR) imaging can be useful in patients with Paget disease for evaluation of the nipple-areolar complex and identification of an additional underlying malignancy in the breast. The appropriate surgical treatment must be carefully selected and individualized on the basis of radiologic findings, especially those obtained with breast MR imaging.

  19. Spatial Correlation Analysis between Particulate Matter 10 (PM10) Hazard and Respiratory Diseases in Chiang Mai Province, Thailand

    NASA Astrophysics Data System (ADS)

    Trang, N. Ha; Tripathi, N. K.

    2014-11-01

    Every year, during dry season, Chiang Mai and other northern provinces of Thailand face the problem of haze which is mainly generated by the burning of agricultural waste and forest fire, contained high percentage of particulate matter. Particulate matter 10 (PM10), being very small in size, can be inhaled easily to the deepest parts of the human lung and throat respiratory functions. Due to this, it increases the risk of respiratory diseases mainly in the case of continuous exposure to this seasonal smog. MODIS aerosol images (MOD04) have been used for four weeks in March 2007 for generating the hazard map by linking to in-situ values of PM10. Simple linear regression model between PM10 and AOD got fair correlation with R2 = 0.7 and was applied to transform PM10 pattern. The hazard maps showed the dominance of PM10 in northern part of Chiang Mai, especially in second week of March when PM10 level was three to four times higher than standard. The respiratory disease records and public health station of each village were collected from Provincial Public Health Department in Chiang Mai province. There are about 300 public health stations out of 2070 villages; hence thiessen polygon was created to determine the representative area of each public health station. Within each thiessen polygon, respiratory disease incident rate (RDIR) was calculated based on the number of patients and population. Global Moran's I was computed for RDIR to explore spatial pattern of diseases through four weeks of March. Moran's I index depicted a cluster pattern of respiratory diseases in 2nd week than other weeks. That made sense for a relationship between PM10 and respiratory diseases infections. In order to examine how PM10 affect the human respiratory system, geographically weighted regression model was used to observe local correlation coefficient between RDIR and PM10 across study area. The result captured a high correlation between respiratory diseases and high level of PM10 in

  20. Correlation of the serum concentrations of tumour necrosis factor and nitric oxide with disease severity in chronic Chagas disease (American trypanosomiasis).

    PubMed

    Pérez-Fuentes, R; López-Colombo, A; Ordóñez-Toquero, G; Gomez-Albino, I; Ramos, J; Torres-Rasgado, E; Salgado-Rosas, H; Romero-Díaz, M; Pulido-Pérez, P; Sánchez-Guillén, M C

    2007-03-01

    Pro-inflammatory cytokines such as tumour necrosis factor (TNF) and nitric oxide (NO) are believed to play an important role in the severity of chronic disease. When evaluated in 71 patients who were seropositive for Trypanosoma cruzi and 50 apparently healthy controls, the mean (S.D.) serum concentrations of both TNF [7.65 (1.32) nu. 4.24 (1.53) ng/ml; P<0.001] and NO [114 (40) nu. 74 (21) microM; P<0.0001] were found to be significantly higher in the patients than in the controls. In addition, patients with chronic, symptomatic disease affecting their hearts--eight with dilated cardiomyopathy [8.82 (1.47) ng TNF/ml; 142 (45) microM NO] and 17 others with electrocardiographic alterations [8.37 (1.26) ng TNF/ml; 134 (53) microM NO]--had significantly higher serum concentrations of these cytokines than 34 patients who were in the asymptomatic, indeterminate phase of the disease [6.38 (1.35) ng TNF/ml; 99 (28) microM NO]. In those infected with T. cruzi, it therefore appears that serum concentrations of TNF and NO correlate with disease severity, indicating that these cytokines play some role in the pathogenesis of chronic Chagas disease.

  1. Regional distribution of synaptic markers and APP correlate with distinct clinicopathological features in sporadic and familial Alzheimer's disease.

    PubMed

    Shinohara, Mitsuru; Fujioka, Shinsuke; Murray, Melissa E; Wojtas, Aleksandra; Baker, Matthew; Rovelet-Lecrux, Anne; Rademakers, Rosa; Das, Pritam; Parisi, Joseph E; Graff-Radford, Neill R; Petersen, Ronald C; Dickson, Dennis W; Bu, Guojun

    2014-05-01

    Recent studies suggest that subcortical structures, including striatum, are vulnerable to amyloid-β accumulation and other neuropathological features in familial Alzheimer's disease due to autosomal dominant mutations. We explored differences between familial and sporadic Alzheimer's disease that might shed light on their respective pathogenic mechanisms. To this end, we analysed 12 brain regions, including neocortical, limbic and subcortical areas, from post-mortem brains of familial Alzheimer's disease (n = 10; age at death: 50.0 ± 8.6 years) with mutations in amyloid precursor protein (APP) or presenilin 1 (PSEN1), sporadic Alzheimer's disease (n = 19; age at death: 84.7 ± 7.8 years), neurologically normal elderly without amyloid-β accumulation (normal ageing; n = 13, age at death: 82.9 ± 10.8 years) and neurologically normal elderly with extensive cortical amyloid-β deposits (pathological ageing; n = 15; age at death: 92.7 ± 5.9 years). The levels of amyloid-β₄₀, amyloid-β₄₂, APP, apolipoprotein E, the synaptic marker PSD95 (now known as DLG4), the astrocyte marker GFAP, other molecules related to amyloid-β metabolism, and tau were determined by enzyme-linked immunosorbent assays. We observed that familial Alzheimer's disease had disproportionate amyloid-β₄₂ accumulation in subcortical areas compared with sporadic Alzheimer's disease, whereas sporadic Alzheimer's disease had disproportionate amyloid-β₄₂ accumulation in cortical areas compared to familial Alzheimer's disease. Compared with normal ageing, the levels of several proteins involved in amyloid-β metabolism were significantly altered in both sporadic and familial Alzheimer's disease; however, such changes were not present in pathological ageing. Among molecules related to amyloid-β metabolism, the regional distribution of PSD95 strongly correlated with the regional pattern of amyloid-β₄₂ accumulation in sporadic Alzheimer's disease and pathological ageing, whereas the

  2. Laser correlation spectroscopy in the diagnosis of tumor diseases of the female reproductive system (preliminary results)

    NASA Astrophysics Data System (ADS)

    Korneeva, A. A.; Sekerskaya, M. N.; Zhordaniya, K. I.; Sapezhinskiy, V. S.; Golubtsova, N. V.; Barmashov, A. E.; Gonchukov, S. A.; Ivanov, A. V.

    2017-01-01

    The study of blood serum of cancer patients by laser correlation spectroscopy to determine the possibility of differentiation of benign and malignant tumors of the female reproductive system. We analyzed the data and assessed the applicability of the method mentioned above target.

  3. Higher minor hemoglobin A2 levels in multiple sclerosis patients correlate with lesser disease severity

    PubMed Central

    Ozcan, Muhammed Emin; Ince, Bahri; Karadeli, Hasan Huseyin; Gedikbasi, Asuman; Asil, Talip; Altinoz, Meric A

    2016-01-01

    Objective To define whether minor adult hemoglobin A2 (HbA2, α2δ2) exerts any protective activity in multiple sclerosis (MS). Methods HbA2 levels were measured in 146 MS patients with high performance liquid chromatography and association with MS Severity Scores (MSSS) were determined. HbA2 associations with blood count parameters were also studied using blood counts evaluated on the same day of high performance liquid chromatography sampling. Routine biochemical parameters were also determined to rule out elusively influential factors, such as anemia and thyroid disorders. Results HbA2 levels negatively correlated with MSSS (Spearman correlation, R: −0.186, P=0.025). Exclusion of confounding factors with a generalized linear model revealed an even stronger negative correlation between HbA2 and MSSS (P<0.001). HbA2 positively correlated with red blood cells (RBCs) (R=0.350, P<0.001) and in turn, RBCs negatively correlated with MSSS (R=−0.180, P=0.031). Average HbA2 levels were highest among patients treated with interferon β1a. Conclusion RBC fragility is increased in MS, and recent data suggest that circulating free Hb contributes to neural injury in MS. HbA2 and its oxidative denaturation product hemichrome A2 enhance RBC membrane stability to a greater extent than do major HbA or hemichrome A. Reductions in ischemic cerebrovascular vascular events are reported in β-thalassemia carriers and HbA2 levels are considerably higher in this population. Episodic declines of cerebral blood flow were shown in bipolar disorder, and we have recently shown a protective role of HbA2 against postpartum episodes in females with bipolar disorder. HbA2’s erythroprotective functions may reduce free Hb and long-term neural injury in MS. PMID:27578976

  4. Nutritional and metabolic correlates of cardiovascular and bone disease in HIV-infected patients.

    PubMed

    Fitch, Kathleen; Grinspoon, Steven

    2011-12-01

    The treatment of HIV infection has dramatically reduced the incidence of AIDS-related illnesses. At the same time, non-AIDS-related illnesses such as cardiovascular and bone disease are becoming more prevalent in this population. The mechanisms of these illnesses are complex and are related in part to the HIV virus, antiretroviral medications prescribed for HIV infection, traditional risk factors exacerbated by HIV, and lifestyle and nutritional factors. Further prospective research is needed to clarify the mechanisms by which HIV, antiretroviral medications, and nutritional abnormalities contribute to bone and cardiovascular disease in the HIV population. Increasingly, it is being recognized that optimizing the treatment of HIV infection to improve immune function and reduce viral load may also benefit the development of non-AIDS-related illnesses such as cardiovascular and bone disease.

  5. Molecular phylogeny of the psittacid herpesviruses causing Pacheco's disease: correlation of genotype with phenotypic expression.

    PubMed

    Tomaszewski, Elizabeth K; Kaleta, Erhard F; Phalen, David N

    2003-10-01

    Fragments of 419 bp of the UL16 open reading frame from 73 psittacid herpesviruses (PsHVs) from the United States and Europe were sequenced. All viruses caused Pacheco's disease, and serotypes of the European isolates were known. A phylogenetic tree derived from these sequences demonstrated that the PsHVs that cause Pacheco's disease comprised four major genotypes, with each genotype including between two and four variants. With the exception of two viruses, the serotypes of the virus isolates could be predicted by the genotypes. Genotypes 1 and 4 corresponded to serotype 1 isolates, genotype 2 corresponded to serotype 2 isolates, and genotype 3 corresponded to serotype 3 isolates. The single serotype 4 virus mapped to genotype 4. DNA from a virus with a unique serotype could not be amplified with primers that amplified DNA from all other PsHVs, and its classification remains unknown. Viruses representing all four genotypes were found in both the United States and Europe, and it was therefore predicted that serotypes 1, 2, and 3 were present in the United States. Serotype 4 was represented by a single European isolate that could not be genetically distinguished from serotype 1 viruses; therefore, the presence of serotype 4 in the United States could not be predicted. Viruses of genotype 4 were found to be the most commonly associated with Pacheco's disease in macaws and conures and were least likely to be isolated in chicken embryo fibroblasts in the United States. All four genotypes caused deaths in Amazon parrots, but genotype 4 was associated with Pacheco's disease only in Amazons in Europe. Genotypes 2, 3, and 4, but not 1, were found in African grey parrots. Although parrots from the Pacific distribution represent a relatively small percentage of the total number of birds with Pacheco's disease, all four genotypes were found to cause disease in these species.

  6. DIVERGENCE, NOT DIVERSITY OF AN ATTENUATED EQUINE LENTIVIRUS VACCINE STRAIN CORRELATES WITH PROTECTION FROM DISEASE

    PubMed Central

    Craigo, Jodi K.; Barnes, Shannon; Cook, Sheila J.; Issel, Charles J.; Montelaro, Ronald C.

    2010-01-01

    We recently reported an attenuated EIAV vaccine study that directly examined the effect of lentiviral envelope sequence variation on vaccine efficacy. The study [1] demonstrated for the first time the failure of an ancestral vaccine to protect and revealed a significant, inverse, linear relationship between envelope divergence and protection from disease. In the current study we examine in detail the evolution of the attenuated vaccine strain utilized in this previous study. We demonstrate here that the attenuated strain progressively evolved during the six-month pre-challenge period and that the observed protection from disease was significantly associated with divergence from the original vaccine strain. PMID:20955830

  7. Antibody responses against SARS coronavirus are correlated with disease outcome of infected individuals.

    PubMed

    Zhang, Linqi; Zhang, Fengwen; Yu, Wenjie; He, Tian; Yu, Jian; Yi, Christopher E; Ba, Lei; Li, Wenhui; Farzan, Michael; Chen, Zhiwei; Yuen, Kwok-Yung; Ho, David

    2006-01-01

    Most of the SARS-CoV-infected patients spontaneously recovered without clinical intervention while a small percentage succumbed to the disease. Here, we characterized temporal changes in N protein-specific and S glycoprotein-specific neutralizing antibody (Nab) responses in infected patients who have either recovered from or succumbed to SARS-CoV infection. Recovered patients were found to have higher and sustainable levels of both N protein-specific and S glycoprotein-specific Nab responses, suggesting that antibody responses likely play an important role in determining the ultimate disease outcome of SARS-CoV-infected patients.

  8. Correlation between cell free DNA levels and medical evaluation of disease progression in systemic lupus erythematosus patients.

    PubMed

    Tug, Suzan; Helmig, Susanne; Menke, Julia; Zahn, Daniela; Kubiak, Thomas; Schwarting, Andreas; Simon, Perikles

    2014-01-01

    High levels of cell free DNA (cfDNA) in human blood plasma have been described in patients with autoimmune diseases. The aim of this study was to determine the levels of cfDNA in systemic lupus erythematosus (SLE) patients and to assess fluctuations of cfDNA concentrations compared to the course of disease progression under standard treatment. Therefore, nuclear cfDNA concentrations in plasma were measured in 59 SLE patients and 59 healthy controls. Follow-up blood plasma was collected from 27 of the 59 SLE patients. Patients were characterised by clinical parameters (antinuclear antibodies (ANA), anti-dsDNA-antibodies, C3, C4, and CRP), SLE disease activity index (SLEDAI) and medical therapy. Our results showed that cfDNA concentrations were significantly higher in SLE patients compared to healthy individuals. Levels of cfDNA assessed in serial samples correlated significantly with the medical evaluation of disease activity in SLE patients. Our results could implicate cfDNA as a global marker for disease activity.

  9. Cleft Palate, Retrognathia and Congenital Heart Disease in Velo-Cardio-Facial Syndrome: A Phenotype Correlation Study

    PubMed Central

    Friedman, Marcia A.; Miletta, Nathanial; Roe, Cheryl; Wang, Dongliang; Morrow, Bernice E.; Kates, Wendy R.; Higgins, Anne Marie; Shprintzen, Robert J.

    2011-01-01

    Objective Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion of approximately 40 genes from one copy of chromosome 22. Expression of the syndrome is a variable combination of over 190 phenotypic characteristics. As of yet, little is known about how these phenotypes correlate with one another or whether there are predictable patterns of expression. Two of the most common phenotypic categories, congenital heart disease and cleft palate, have been proposed to have a common genetic relationship to the deleted T-box 1 gene (TBX1). The purpose of this study is to determine if congenital heart disease and cleft palate are correlated in a large cohort of human subjects with VCFS. Methods This study is a retrospective chart review including 316 Caucasian non-Hispanic subjects with FISH or CGH microarray confirmed chromosome 22q11.2 deletions. All subjects were evaluated by the interdisciplinary team at the Velo-Cardio-Facial Syndrome International Center at Upstate Medical University, Syracuse, NY. Each combination of congenital heart disease, cleft palates, and retrognathia was analyzed by chi square or Fisher exact test. Results For all categories of congenital heart disease and cleft palate or retrognathia no significant associations were found, with the exception of submucous cleft palate and retrognathia (nominal p=0.0325) and occult submucous cleft palate and retrognathia (nominal p=0.000013). Conclusions Congenital heart disease and cleft palate do not appear to be correlated in human subjects with VCFS despite earlier suggestions from animal models. Possible explanations include modification of the effect of TBX1 by genes outside of the 22q11.2 region that may further influence the formation of the palate or heart, or the presence of epigenetic factors that may effect genes within the deleted region, modifying genes elsewhere, or polymorphisms on the normal copy of chromosome 22. Lastly, it is possible that TBX1 plays a role in palate formation in some

  10. Decreased Gaq expression in T cells correlates with enhanced cytokine production and disease activity in systemic lupus erythematosus

    PubMed Central

    Luo, Jiao; Yu, Bing; Qian, Hongyan; Duan, Lihua; Shi, Guixiu

    2016-01-01

    Aberrant T cell immune responses appear central to the development of systemic lupus erythematosus (SLE). We previously reported that Gαq, the alpha subunit of Gq, regulates T and B cell immune responses, promoting autoimmunity. To address whether Gαq contributes to the pathogenesis of SLE, Gαq mRNA expression was studied using real time-PCR in PBMCs and T cells from SLE patients as well as age- and sex-matched healthy controls. Our results showed that Gαq mRNA expression was decreased in PBMCs and T cells from SLE patients compared to healthy individuals. Correlation analyses showed that Gαq expression in T cells from SLE patients was associated with disease severity (as per SLE Disease Activity Index), the presence of lupus nephritis, and expression of Th1, Th2 and Th17 cytokines. In keeping with clinical results, T-helper cell subsets (Th1, Th2 and Th17) were over-represented in Gαq knockout mice. In addition, Gαq expression in SLE T cells was negatively correlated with the expression of Bcl-2, an anti-apoptotic gene, and positively correlated with the expression of Bax, a pro-apoptotic gene. These data suggest that reduced Gαq levels in T cells may promote enhanced and prolonged T cell activation, contributing to the clinical manifestations of SLE. PMID:27965465

  11. Significant positive correlation between sunshine and lactase nonpersistence in Europe may implicate both in similarly altering risks for some diseases.

    PubMed

    Szilagyi, Andrew; Leighton, Henry; Burstein, Barry; Shrier, Ian

    2011-01-01

    Decreasing latitude and increasing frequency of population lactase nonpersistence have been reported to diminish risks for several diseases, but the reason for overlap has not been explained. We evaluate, relationships between calculated national annual ultraviolet light B (UVB) exposure, latitude, and national lactose digestion frequencies. Annual UVB exposure and latitude were based on weighted averages from several cities in different countries. Lactase distribution status was based on published data that have been used previously to derive relations with diseases. We compare univariate regression analyses (r(2)(adj), slope) of percentage of lactase nonpersistence with UVB or latitude. We determine, differences between European and non-European sources by multiregression analysis of independent variables. Correlation between UVB and latitude is high (r(2) = 0.89), and between percentage of lactase nonpersistence and either latitude or UVB the correlation is moderately strong with r(2) = 0.51 and 0.46, respectively, with P ≤ 0.01 for both. A more detailed analysis shows that correlations between percentage of lactase nonpersistence and UVB are only significant in Europe, r(2) = 0.59, P < 0.001, whereas outside Europe: r(2) = 0.06, P = 0.16. These relationships raise hypothetical explanations to account for the observed overlap in similar risk modification by the 2 variables.

  12. Mixed-genotype white spot syndrome virus infections of shrimp are inversely correlated with disease outbreaks in ponds.

    PubMed

    Hoa, Tran Thi Tuyet; Zwart, Mark P; Phuong, Nguyen T; Oanh, Dang T H; de Jong, Mart C M; Vlak, Just M

    2011-03-01

    Outbreaks of white spot syndrome virus (WSSV) in shrimp culture and the relationship between the virus and virulence are not well understood. Here, we provide evidence showing that WSSV mixed-genotype infections correlate with lower outbreak incidence and that disease outbreaks correlate with single-genotype infections. We tested 573 shrimp samples from 81 shrimp ponds in the Mekong delta with outbreak or non-outbreak status. The variable number tandem repeat (VNTR) loci of WSSV were used as molecular markers for the characterization of single- and mixed-genotype infections. The overall prevalence of mixed-genotype WSSV infections was 25.7 %. Non-outbreak ponds had a significantly higher frequency of mixed-genotype infections than outbreak ponds for all VNTR loci, both at the individual shrimp as well as at the pond level. The genetic composition of WSSV populations appears to correlate with the health status of shrimp culture in ponds. The causal relationship between genotypic diversity and disease outbreaks can now be experimentally approached.

  13. Correlating reduction in fungicide sensitivity in C. beticola with loss of disease control

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Practical resistance can be defined as a situation in which reduced sensitivity (resistance) of a fungal pathogen to a fungicide results in poor disease control in the field and the resistance is confirmed by laboratory testing. Although we have many years of data showing reduced sensitivity of C. ...

  14. Behavioral and Neurophysiological Correlates of Striatal Dopamine Depletion: A Rodent Model of Parkinson's Disease

    ERIC Educational Resources Information Center

    Plowman, Emily K.; Kleim, Jeffrey A.

    2011-01-01

    Both limb and cranial motor functions are adversely impacted by Parkinson's disease (PD). While current pharmacological and surgical interventions are effective in alleviating general limb motor symptoms of PD, they have failed to provide significant benefit for cranial motor functions. This suggests that the neuropathologies mediating limb and…

  15. Physiological Correlates of Intellectual Function in Children with Sickle Cell Disease: Hypoxaemia, Hyperaemia and Brain Infarction

    ERIC Educational Resources Information Center

    Hogan, Alexandra M.; Pit-ten Cate, Ineke M.; Vargha-Khadem, Faraneh; Prengler, Mara; Kirkham, Fenella J.

    2006-01-01

    Lowered intelligence relative to controls is evident by mid-childhood in children with sickle cell disease. There is consensus that brain infarct contributes to this deficit, but the subtle lowering of IQ in children with normal MRI scans might be accounted for by chronic systemic complications leading to insufficient oxygen delivery to the brain.…

  16. Correlates of lung/heart ratio of thallium-201 in coronary artery disease

    SciTech Connect

    Homma, S.; Kaul, S.; Boucher, C.A.

    1987-10-01

    We studied 306 patients with chest pain (262 with coronary artery disease and 44 with no coronary artery disease) to determine which of 23 clinical, exercise, thallium, and angiographic variables best discriminate between patients with increased lung/heart ratios of thallium versus those with normal ratios. Normal lung/heart ratio values were defined using an additional 45 subjects with less than 1% probability of coronary artery disease. The number of diseased vessels was the best discriminator between patients with increased ratios versus those with normal ratios. Double product at peak exercise, number of segments with abnormal wall motion, patient gender, and duration of exercise were also significant discriminators. Using discriminant function analysis these variables could correctly identify 81% of cases with increased lung/heart ratios and 72% of cases with normal ratios. These results indicate that an increased lung/heart ratio of thallium reflects exercise-induced left ventricular dysfunction and affords a better understanding of why this thallium parameter is a powerful prognostic indicator in patients with chest pain.

  17. Bancroftian filariasis: spatial patterns, environmental correlates and landscape predictors of disease risk.

    PubMed

    Hassan, Ali N

    2004-08-01

    Lymphatic filariasis has been identified as the second leading cause of permanent and long-term disability. This article is an attempt to discuss the disease spatial context in light of current interest in GIS and satellite remote sensing. Field validation of outputs obtained through the application of these technologies in the Nile Delta, Egypt is also summarized.

  18. Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy.

    PubMed

    Fall, Brent; Scott, C Ronald; Mauer, Michael; Shankland, Stuart; Pippin, Jeffrey; Jefferson, Jonathan A; Wallace, Eric; Warnock, David; Najafian, Behzad

    2016-01-01

    Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for podocyturia. Most of the Fabry patients and many healthy subjects had podocyturia. The number of podocytes per gram of urine creatinine (UPodo/g Cr) was 3.6 fold greater in Fabry patients (3,741 ± 2796; p = 0.001) than healthy subjects (1,040 ± 972). Fabry patients with normoalbuminuria and normoproteinuria had over 2-fold greater UPodo/g Cr than healthy subjects (p = 0.048). UPodo/gCr was inversely related to eGFR in male patients (r = -0.69, p = 0.003). UPodo/gCr was directly related to urine protein creatinine ratio (r = 0.33; p = 0.04) in all Fabry patients. These studies confirm increased podocyturia in Fabry disease, even when proteinuria and albuminuria are absent. Podocyturia correlates with clinical severity of Fabry nephropathy, and potentially may be of prognostic value.

  19. Mining Outcome-relevant Brain Imaging Genetic Associations via Three-way Sparse Canonical Correlation Analysis in Alzheimer's Disease.

    PubMed

    Hao, Xiaoke; Li, Chanxiu; Du, Lei; Yao, Xiaohui; Yan, Jingwen; Risacher, Shannon L; Saykin, Andrew J; Shen, Li; Zhang, Daoqiang

    2017-03-14

    Neuroimaging genetics is an emerging field that aims to identify the associations between genetic variants (e.g., single nucleotide polymorphisms (SNPs)) and quantitative traits (QTs) such as brain imaging phenotypes. In recent studies, in order to detect complex multi-SNP-multi-QT associations, bi-multivariate techniques such as various structured sparse canonical correlation analysis (SCCA) algorithms have been proposed and used in imaging genetics studies. However, associations between genetic markers and imaging QTs identified by existing bi-multivariate methods may not be all disease specific. To bridge this gap, we propose an analytical framework, based on three-way sparse canonical correlation analysis (T-SCCA), to explore the intrinsic associations among genetic markers, imaging QTs, and clinical scores of interest. We perform an empirical study using the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort to discover the relationships among SNPs from AD risk gene APOE, imaging QTs extracted from structural magnetic resonance imaging scans, and cognitive and diagnostic outcomes. The proposed T-SCCA model not only outperforms the traditional SCCA method in terms of identifying strong associations, but also discovers robust outcome-relevant imaging genetic patterns, demonstrating its promise for improving disease-related mechanistic understanding.

  20. Erythrocyte glutathione transferase: a non-antibody biomarker for systemic sclerosis, which correlates with severity and activity of the disease

    PubMed Central

    Fabrini, R; Rosato, E; Gigante, A; Bocedi, A; Cianci, R; Barbano, B; Del Grosso, E; Ricci, F; Zingaretti, V; Salsano, F; Ricci, G

    2013-01-01

    Erythrocyte glutathione transferase (e-GST) is a detoxifying enzyme hyper-expressed in nephropathic patients and used recently as a biomarker for blood toxicity. Systemic sclerosis (SSc) is characterized by endothelial dysfunction and fibrosis of the skin and internal organs. Renal involvement is frequent in SSc patients. Here we show that e-GST is hyper-expressed in SSc patients (n=102) and correlates (R2=0.49, P<0.0001) with the Medsger DSS and DAI Valentini indices that quantify the severity and activity of this disease. Interestingly, e-GST does not correlate with the impairment of kidney or other specific organs taken separately. e-GST hyper-expression seems to be linked to the presence of a factor (i.e., toxin) that triggers the autoimmune disease, and not to the damage of specific organs or to oxidative stress. e-GST may be proposed as an innovative non-antibody biomarker for SSc useful to check the progress of this disease and the efficiency of new therapeutic strategies. PMID:23887627

  1. Urinary Podocyte Loss Is Increased in Patients with Fabry Disease and Correlates with Clinical Severity of Fabry Nephropathy

    PubMed Central

    Fall, Brent; Scott, C. Ronald; Mauer, Michael; Shankland, Stuart; Pippin, Jeffrey; Jefferson, Jonathan A.; Wallace, Eric; Warnock, David; Najafian, Behzad

    2016-01-01

    Chronic kidney disease is a major complication of Fabry disease. Podocytes accumulate globotriaosylceramide inclusions more than other kidney cell types in Fabry patients. Podocyte injury occurs early in age, and is progressive. Since injured podocytes detach into the urine (podocyturia), we hypothesized that podocyturia would increase in Fabry patients and correlate with clinical severity of Fabry nephropathy. Urine specimens from 39 Fabry patients and 24 healthy subjects were evaluated for podocyturia. Most of the Fabry patients and many healthy subjects had podocyturia. The number of podocytes per gram of urine creatinine (UPodo/g Cr) was 3.6 fold greater in Fabry patients (3,741 ± 2796; p = 0.001) than healthy subjects (1,040 ± 972). Fabry patients with normoalbuminuria and normoproteinuria had over 2-fold greater UPodo/g Cr than healthy subjects (p = 0.048). UPodo/gCr was inversely related to eGFR in male patients (r = -0.69, p = 0.003). UPodo/gCr was directly related to urine protein creatinine ratio (r = 0.33; p = 0.04) in all Fabry patients. These studies confirm increased podocyturia in Fabry disease, even when proteinuria and albuminuria are absent. Podocyturia correlates with clinical severity of Fabry nephropathy, and potentially may be of prognostic value. PMID:27992580

  2. Cirrhotic cardiomyopathy: is there any correlation between the stage of cardiac impairment and the severity of liver disease?

    PubMed Central

    Hammami, Rania; Boudabbous, Mouna; Jdidi, Jihen; Trabelsi, Fatma; Mroua, Fakher; Kallel, Rahma; Amouri, Ali; Abid, Dorra; Tahri, Nabil; Abid, Leila; Kammoun, Samir

    2017-01-01

    ABSTRACT Cirrhotic cardiomyopathy is associated with poor prognosis and risk of acute heart failure after liver transplantation or interventional procedures. We aimed to assess the relationship between the severity of cardiac impairment and hepatic disease. Eighty patients and eighty controls underwent echocardiography, tissue Doppler imaging and speckle tracking measures. We assess the correlation between echocardiographic parameters and Child and MELD scores. Systolic parameters function (s wave, p < 0.001) and global longitudinal strain (p < 0.001) as well as diastolic parameters were significantly more impaired in cirrhotic patients compared to controls. There were no differences among the different groups in ‘Child score’ regarding systolic function as well as diastolic function. Paradoxically, the left atrium size correlated positively to both Child (p = 0.01, r = 0.26) and MELD scores (p = 0.02, r = 0.24). Left ventricular ejection fraction was significantly lower in decompensated patients as compared to compensated patients(p = 0.02).. We did not identify any association between severity of liver disease and cardiac dysfunction. Therefore, a transthoracic echocardiography should be performed in all cirrhotic patients before interventional and surgical procedures regardless of the severity of liver disease. PMID:28245727

  3. Fractal mechanisms and heart rate dynamics. Long-range correlations and their breakdown with disease

    NASA Technical Reports Server (NTRS)

    Peng, C. K.; Havlin, S.; Hausdorff, J. M.; Mietus, J. E.; Stanley, H. E.; Goldberger, A. L.

    1995-01-01

    Under healthy conditions, the normal cardiac (sinus) interbeat interval fluctuates in a complex manner. Quantitative analysis using techniques adapted from statistical physics reveals the presence of long-range power-law correlations extending over thousands of heartbeats. This scale-invariant (fractal) behavior suggests that the regulatory system generating these fluctuations is operating far from equilibrium. In contrast, it is found that for subjects at high risk of sudden death (e.g., congestive heart failure patients), these long-range correlations break down. Application of fractal scaling analysis and related techniques provides new approaches to assessing cardiac risk and forecasting sudden cardiac death, as well as motivating development of novel physiologic models of systems that appear to be heterodynamic rather than homeostatic.

  4. Increased 8,12-iso-iPF2alpha-VI in Alzheimer's disease: correlation of a noninvasive index of lipid peroxidation with disease severity.

    PubMed

    Praticò, D; Clark, C M; Lee, V M; Trojanowski, J Q; Rokach, J; FitzGerald, G A

    2000-11-01

    The isoprostane 8,12-iso-iPF2alpha-VI is a sensitive and specific marker of in vivo lipid peroxidation. We found elevated levels in the urine, blood, and cerebrospinal fluid of patients with Alzheimer's disease (AD) that correlated with measures of cognitive and functional impairment, established biomarkers of AD pathology (cerebrospinal fluid tau and amyloid) and the number of apolipoprotein E epsilon4 alleles. These results suggest that 8,12-iso-iPF2alpha-VI is a useful biomarker of oxidative damage in AD.

  5. Correlation of toddlers' serum lipoprotein(a) concentration with parental values and grandparents' coronary heart disease: the STRIP baby study.

    PubMed

    Routi, T; Rönnemaa, T; Jokinen, E; Viikari, J; Niinikoski, H; Leino, A; Simell, O

    1996-04-01

    The correlation between lipoprotein(a) (Lp(a)) concentrations in children aged 7-24 months and their family members was determined and the association between the Lp(a) values of the children and a family history of coronary heart disease (CHD) was assessed. The Lp(a) values of the children correlated strongly with midparent Lp(a) values as early as at 7 months of age (r = 0.54 to 0.59, p < 0.0001). This correlation was stronger than the correlation of serum total cholesterol and total cholesterol corrected for Lp(a)-cholesterol between children and parents. None of the parents had CHD. The median Lp(a) concentration of the parents with a family history of CHD was significantly higher than that of parents with no such history (111 vs 87 mg/1, p = 0.024). However, the children's Lp(a) levels were not associated with CHD in their grandparents. The genetic dependence of the Lp(a) concentration is already evident in infancy. The Lp(a) concentration in young parents, but not in their 24-month-old children, is associated with CHD in grandparents. This may be explained by a dilution of the genetic influence on Lp(a) over two generations.

  6. Nocturnal Oxygen Desaturation Index is Inversely Correlated with Airflow Limitation in Patients with Chronic Obstructive Pulmonary Disease.

    PubMed

    Tamai, Koji; Matsuoka, Hirofumi; Suzuki, Yujiro; Yoshimatsu, Harukazu; Masuya, Daiki; Nakashima, Nariyasu; Okada, Nobuhiko; Oda, Nao; Inoue, Sayaka; Koma, Yasuko; Otsuka, Akiko

    2016-01-01

    The concurrent diagnosis of chronic obstructive pulmonary disease (COPD) and sleep apnoea-hypopnoea syndrome (SAHS) (overlap syndrome), can contribute to worsening respiratory symptoms, but whether the severity of COPD is associated with co-morbid SAHS is unknown. We investigated whether the severity of COPD is associated with the complication of SAHS by examination of nocturnal oximetry as an alternative to polysomnography. Patients with COPD concurrently completed nocturnal oximetry, pulmonary function tests, a COPD assessment test, an Epworth sleepiness scale and a hospital anxiety and depression scale to evaluate the severity of COPD and possible concurrent presence of SAHS. We retrospectively analysed the data to assess correlation between the oxygen desaturation index (ODI) and each clinical variables and evaluated the predictors of ODI ≥ 15. This study included 103 patients (91 males, 88%) with a mean age of 72 ± 8 years and body mass index of 22 ± 3 kg/m(2). ODI was positively correlated with FEV1, FEV1/FVC and FEV1% predicted, which meant that ODI was inversely correlated with airflow limitation. Univariate logistic regression analysis revealed that FEV1% predicted and FEV1/FVC were predictors of ODI ≥ 15. ODI is inversely correlated with airflow limitation and milder COPD patients may have co-morbid SAHS.

  7. Correlation of stress with outcome of radioiodine therapy for Graves disease

    SciTech Connect

    Stewart, T.; Rochon, J.; Lenfestey, R.; Wise, P.

    1985-06-01

    Between November 1965 and December 1983, 293 patients were treated for Graves disease using /sup 131/I. All patients were asked to identify a stressful event antedating the onset of overt clinical symptoms. Eighty-one patients were able to do this (27.6%). Two hundred forty-four patients received a single treatment, 49 required two or more treatments. Patients with stress initiating the symptoms of Graves disease became hypothyroid earlier, 50% at 12 mo compared with 36 mo for the nonstress group. At 10 yr 5% of the stress group remained euthyroid compared with 17% nonstress. The authors conclude that stress in the 12 mo or less before the onset of clinical symptoms potentiates the development of hypothyroidism induced by a standard dose of radioiodine.

  8. The genetic background of inflammatory bowel disease: from correlation to causality.

    PubMed

    Uniken Venema, Werna Tc; Voskuil, Michiel D; Dijkstra, Gerard; Weersma, Rinse K; Festen, Eleonora Am

    2017-01-01

    Recent studies have greatly improved our insight into the genetic background of inflammatory bowel disease (IBD). New high-throughput technologies and large-scale international collaborations have contributed to the identification of 200 independent genetic risk loci for IBD. However, in most of these loci, it is unclear which gene conveys the risk for IBD. More importantly, it is unclear which variant within or near the gene is causal to the disease. Using targeted GWAS, imputation, resequencing of risk loci, and in silico fine-mapping of densely typed loci, several causal variants have been identified in IBD risk genes, and various pathological pathways have been uncovered. Current research in the field of IBD focuses on the effect of these causal variants on gene expression and protein function. However, more elements than only the genome must be taken into account to disentangle the multifactorial pathology of IBD. The genetic risk loci identified to date only explain a small part of genetic variance in disease risk. Currently, large multi-omics studies are incorporating factors ranging from the gut microbiome to the environment. In this review, we present the progress that has been made in IBD genetic research and stress the importance of studying causality to increase our understanding of the pathogenesis of IBD. We highlight important causal genetic variants in the candidate genes NOD2, ATG16L1, IRGM, IL23R, CARD9, RNF186, and PRDM1. We describe their downstream effects on protein function and their direct effects on the gut immune system. Furthermore, we discuss the future role of genetics in unravelling disease mechanisms in IBD. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  9. Assessment of Interleukin 16 Serum Levels and Skin Expression in Psoriasis Patients in Correlation with Clinical Severity of the Disease

    PubMed Central

    Purzycka-Bohdan, Dorota; Szczerkowska-Dobosz, Aneta; Zablotna, Monika; Wierzbicka, Justyna; Piotrowska, Anna; Zmijewski, Michal A.; Nedoszytko, Boguslaw; Nowicki, Roman

    2016-01-01

    Interleukin 16 (IL-16) has been described as a significant cytokine involved in the recruitment of CD4+ cells during inflammation; however, its potential role in psoriasis has not been defined. Our aim was to investigate the IL-16 serum levels and IL-16 mRNA skin expression in psoriasis patients in correlation with disease severity and mRNA skin expression for CD4. Moreover, the IL-16 skin localization was assessed and the -295 T/C IL-16 polymorphism was analyzed. For this exploratory, observational, and cross-sectional study, 97 unrelated patients with chronic plaque type psoriasis and 104 healthy controls were enrolled. IL-16 serum levels were significantly increased in patients compared with controls (P = 0.000022) and positively correlated with Psoriasis Area and Severity Index (r = 0.34, P = 0.0007), Body Surface Area (r = 0.34, P = 0.01) and were significantly higher in individuals with moderate to severe psoriasis (P = 0.0029). There was no significant correlation between IL-16 serum levels and Dermatology Quality of Life Index and no differences in genotype and allele frequencies for -295 T/C IL-16 polymorphism. The expression of IL-16 (mRNA and protein) was elevated in the margin of psoriatic skin while statistically significant increase in IL-16 immunoreactivity, but not in mRNA level, was observed within plaques. Furthermore, the IL-16 mRNA levels within psoriatic lesions positively correlated with the levels of CD4 mRNA, but not with Psoriasis Area and Severity Index. In conclusion, our data revealed an association between circulating IL-16 and severity of psoriasis which indicates that this cytokine could serve as a potential marker of disease activity. However, further investigations are required. PMID:27788245

  10. Profile and Correlates of Health-related Quality of Life in Chinese Patients with Coronary Heart Disease

    PubMed Central

    Wang, Ling; Wu, Yi-Qun; Tang, Xun; Li, Na; He, Liu; Cao, Yang; Chen, Da-Fang; Hu, Yong-Hua

    2015-01-01

    Background: Although coronary heart disease (CHD) is one of the major cardiovascular diseases, risk factors associated with the health-related quality of life (HRQoL) of CHD patients remain unclear. The present study was designed to determine the profile and significant factors of the HRQoL in CHD patients. Methods: A cross-sectional study was conducted in rural communities of Fangshan District, Beijing, China. Socio-demographic, lifestyle, and comorbidity information of CHD patients were collected by a structured questionnaire and medical records. HRQoL was measured using European Quality of Life 5-dimensions (EQ-5D) scale and EQ Visual Analog Scale (EQ-VAS). Multiple linear and logistic regressions were performed to explore the association of potential risk factors with HRQoL scores and each EQ-5D, respectively. Results: Totally, 1928 CHD patients (mean age 61.64 ± 9.24 years; female:male = 2.4:1) were enrolled in the study. The mean score of EQ-5D index and EQ-VAS were 0.889 ± 0.172 and 71.56 ± 17.65, respectively. Multiple linear regression revealed that marital status, physical activity, moderate alcohol drinking, and family's population were positive independent correlates of EQ-VAS, whereas diabetes mellitus and stroke were negative independent correlates (all P < 0.05). Age and stroke were negatively while physical activity, moderate alcohol drinking, family's population and household income were positively correlated with EQ-5D index (all P < 0.05) independently. In addition, each of the five HRQoL dimensions had various specific determinants, including obesity, underweight, smoking or education. Conclusions: Findings of the study highlight certain socio-demographic, lifestyle factors, and comorbid stroke or diabetes mellitus as correlates of HRQoL in Chinese CHD patients. Large-scale cohort studies should be carried out to confirm our results in the future. PMID:26168822

  11. Radiographic Evaluation of Valvular Heart Disease With Computed Tomography and Magnetic Resonance Correlation.

    PubMed

    Lempel, Jason K; Bolen, Michael A; Renapurkar, Rahul D; Azok, Joseph T; White, Charles S

    2016-09-01

    Valvular heart disease is a group of complex entities with varying etiologies and clinical presentations. There are a number of imaging tools available to supplement clinical evaluation of suspected valvular heart disease, with echocardiography being the most common and clinically established, and more recent emergence of computed tomography and magnetic resonance imaging as additional supportive techniques. Yet even with these newer and more sophisticated modalities, chest radiography remains one of the earliest and most common diagnostic examinations performed during the triage of patients with suspected cardiac dysfunction. Recognizing the anatomic and pathologic features of cardiac radiography including the heart's adaptation to varying hemodynamic changes can provide clues to the radiologist regarding the underlying etiology. In this article, we will elucidate several principles relating to chamber modifications in response to pressure and volume overload as well as radiographic appearances associated with pulmonary fluid status and cardiac dysfunction. We will also present a pattern approach to optimize analysis of the chest radiograph for valvular heart disease, which will help guide the radiologist down a differential diagnostic pathway and create a more meaningful clinical report.

  12. Gallstones: A Worldwide Multifaceted Disease and Its Correlations with Gallbladder Carcinoma

    PubMed Central

    Sharma, Raj Kumar; Sonkar, Kanchan; Sinha, Neeraj; Rebala, Pradeep; Albani, Ahmad Ebrah; Behari, Anu; Reddy, Duvvuri Nageshwar; Farooqui, Alvina; Kapoor, Vinay Kumar

    2016-01-01

    Background Gallstones (GS) associated diseases are among the most recurrent and frequent diseases delineated in India and United Arab Emirates. Several reports suggest that the association of GS with gallbladder cancer (GBC) is very high in Northern part of India; however, its occurrence in UAE and Southern part of India is notably low. Therefore, in the present study, we aimed to perform compositional analysis of GS in three different geographical areas by Solid State Nuclear Magnetic Resonance and Fourier Transformed Infrared spectroscopy. Methods Natural abundance 13C cross polarization magic angle spinning Nuclear Magnetic Resonance and Fourier Transform Infrared spectroscopy is employed for the analysis of human gallstone. Results Cholesterol, bilirubin and calcium carbonate were present in variant concentrations in GS obtained from three different geographical regions. Cholesterol was present predominantly in gallstones from North India. Bilirubin was found to be a main constituent in gallstones pertaining to South India. Whereas GS from UAE showed both cholesterol and bilirubin as their major constituents. Calcium carbonate was found in varying concentrations in gallstones acquired from different regions. Conclusion Variation in environmental condition and dietary habits may contribute and affect the GS formation. Alterations in bile composition influence the GB and augment the crystallization of cholesterol. Analysis of different geographical regions GS could be an important stride to understand the etiology of GS diseases. PMID:27832205

  13. Using a data mining approach to discover behavior correlates of chronic disease: a case study of depression.

    PubMed

    Yoon, Sunmoo; Taha, Basirah; Bakken, Suzanne

    2014-01-01

    The purposes of this methodological paper are: 1) to describe data mining methods for building a classification model for a chronic disease using a U.S. behavior risk factor data set, and 2) to illustrate application of the methods using a case study of depressive disorder. Methods described include: 1) six steps of data mining to build a disease model using classification techniques, 2) an innovative approach to analyzing high-dimensionality data, and 3) a visualization strategy to communicate with clinicians who are unfamiliar with advanced statistics. Our application of data mining strategies identified childhood experience living with mentally ill and sexual abuse, and limited usual activity as the strongest correlates of depression among hundreds variables. The methods that we applied may be useful to others wishing to build a classification model from complex, large volume datasets for other health conditions.

  14. Germ-line mutations in the neurofibromatosis 2 gene: Correlations with disease severity and retinal abnormalities

    SciTech Connect

    Parry, D.M.; Kaiser-Kupfer, M.; Eldridge, R.

    1996-09-01

    Neurofibromatosis 2 (NF2) features bilateral vestibular schwannomas, other benign neural tumors, and cataracts. Patients in some families develop many tumors at an early age and have rapid clinical progression, whereas in other families, patients may not have symptoms until much later and vestibular schwannomas may be the only tumors. The NF2 gene has been cloned from chromosome 22q; most identified germ-line mutations result in a truncated protein and severe NF2. To look for additional mutations and clinical correlations, we used SSCP analysis to screen DNA from 32 unrelated patients. We identified 20 different mutations in 21 patients (66%): 10 nonsense mutations, 2 frameshifts, 7 splice-site mutations, and 1 large in-frame deletion. Clinical information on 47 patients from the 21 families included ages at onset and at diagnosis, numbers of meningiomas, spinal and skin tumors, and presence of cataracts and retinal abnormalities. We compared clinical findings in patients with nonsense or frameshift mutations to those with splice-site mutations. When each patient was considered as an independent random event, the two groups differed (P {le} .05) for nearly every variable. Patients with nonsense or frameshift mutations were younger at onset and at diagnosis and had a higher frequency and mean number of tumors, supporting the correlation between nonsense and frameshift mutations and severe NF2. When each family was considered as an independent random event, statistically significant differences between the two groups were observed only for mean ages at onset and at diagnosis. A larger data set is needed to resolve these discrepancies. We observed retinal hamartomas and/or epiretinal membranes in nine patients from five families with four different nonsense mutations. This finding, which may represent a new genotype-phenotype correlation, merits further study. 58 refs., 2 tabs.

  15. Muscle histopathology in nebulin-related nemaline myopathy: ultrastrastructural findings correlated to disease severity and genotype

    PubMed Central

    2014-01-01

    Nemaline myopathy (NM) is a rare congenital myopathy characterised by hypotonia, muscle weakness, and often skeletal muscle deformities with the presence of nemaline bodies (rods) in the muscle biopsy. The nebulin (NEB) gene is the most commonly mutated and is thought to account for approximately 50% of genetically diagnosed cases of NM. We undertook a detailed muscle morphological analysis of 14 NEB-mutated NM patients with different clinical forms to define muscle pathological patterns and correlate them with clinical course and genotype. Three groups were identified according to clinical severity. Group 1 (n = 5) comprises severe/lethal NM and biopsy in the first days of life. Group 2 (n = 4) includes intermediate NM and biopsy in infancy. Group 3 (n = 5) comprises typical/mild NM and biopsy in childhood or early adult life. Biopsies underwent histoenzymological, immunohistochemical and ultrastructural analysis. Fibre type distribution patterns, rod characteristics, distribution and localization were investigated. Contractile performance was studied in muscle fibre preparations isolated from seven muscle biopsies from each of the three groups. G1 showed significant myofibrillar dissociation and smallness with scattered globular rods in one third of fibres; there was no type 1 predominance. G2 presented milder sarcomeric dissociation, dispersed or clustered nemaline bodies, and type 1 predominance/uniformity. In contrast, G3 had well-delimited clusters of subsarcolemmal elongated rods and type 1 uniformity without sarcomeric alterations. In accordance with the clinical and morphological data, functional studies revealed markedly low forces in muscle bundles from G1 and a better contractile performance in muscle bundles from biopsies of patients from G2, and G3. In conclusion NEB-mutated NM patients present a wide spectrum of morphological features. It is difficult to establish firm genotype phenotype correlation. Interestingly, there was a correlation

  16. Clinical correlations of infliximab trough levels and antibodies to infliximab in South Korean patients with Crohn’s disease

    PubMed Central

    Oh, Eun Hye; Ko, Dae-Hyun; Seo, Hyungil; Chang, Kiju; Kim, Gwang-Un; Song, Eun Mi; Seo, Myeongsook; Lee, Ho-Su; Hwang, Sung Wook; Yang, Dong-Hoon; Ye, Byong Duk; Byeon, Jeong-Sik; Myung, Seung-Jae; Yang, Suk-Kyun; Park, Sang Hyoung

    2017-01-01

    AIM To investigate the clinical implications of infliximab trough levels (IFX-TLs) and antibodies to infliximab (ATI) levels in Crohn’s disease (CD) patients in Asian countries. METHODS IFX-TL and ATI level were measured using prospectively collected samples obtained with informed consent from CD patients being treated at Asan Medical Center, South Korea. We analyzed the correlations between IFX-TLs/ATI levels and the clinical activity of CD (quiescent vs active disease) based on the CD activity index, C-reactive protein level, and physician’s judgment of patients’ clinical status at enrollment. The impact of concomitant immunomodulators was also investigated. RESULTS This study enrolled 138 patients with CD (84 with quiescent and 54 with active disease). In patients with quiescent and active diseases, the median IFX-TLs were 1.423 μg/mL and 0.163 μg/mL, respectively (P < 0.001) and the median ATI levels were 8.064 AU/mL and 11.209 AU/mL, respectively (P < 0.001). In the ATI-negative and -positive groups, the median IFX-TLs were 1.415 μg/mL and 0.141 μg/mL, respectively (P < 0.001). In patients with and without concomitant immunomodulator use, there were no differences in IFX-TLs (0.632 μg/mL and 1.150 μg/mL, respectively; P = 0.274) or ATI levels (8.655 AU/mL and 9.017 AU/mL, respectively; P = 0.083). CONCLUSION IFX-TL/ATI levels were well correlated with the clinical activity in South Korean CD patients. Our findings support the usefulness of IFX-TLs/ATI levels in treating CD patients receiving IFX in clinical practice. PMID:28293096

  17. Disease quantification in dermatology: in vivo near-infrared spectroscopy measures correlate strongly with the clinical assessment of psoriasis severity

    NASA Astrophysics Data System (ADS)

    Greve, Tanja Maria; Kamp, Søren; Jemec, Gregor B. E.

    2013-03-01

    Accurate documentation of disease severity is a prerequisite for clinical research and the practice of evidence-based medicine. The quantification of skin diseases such as psoriasis currently relies heavily on clinical scores. Although these clinical scoring methods are well established and very useful in quantifying disease severity, they require an extensive clinical experience and carry a risk of subjectivity. We explore the opportunity to use in vivo near-infrared (NIR) spectra as an objective and noninvasive method for local disease severity assessment in 31 psoriasis patients in whom selected plaques were scored clinically. A partial least squares (PLS) regression model was used to analyze and predict the severity scores on the NIR spectra of psoriatic and uninvolved skin. The correlation between predicted and clinically assigned scores was R=0.94 (RMSE=0.96), suggesting that in vivo NIR provides accurate clinical quantification of psoriatic plaques. Hence, NIR may be a practical solution to clinical severity assessment of psoriasis, providing a continuous, linear, numerical value of severity.

  18. Sonographic assessment of carpal tunnel syndrome in rheumatoid arthritis: prevalence and correlation with disease activity.

    PubMed

    Karadag, Omer; Kalyoncu, Umut; Akdogan, Ali; Karadag, Yesim Sucullu; Bilgen, Sule Apras; Ozbakır, Senay; Filippucci, Emilio; Kiraz, Sedat; Ertenli, Ihsan; Grassi, Walter; Calgüneri, Meral

    2012-08-01

    Carpal tunnel syndrome (CTS) is one of the most frequent extra-articular manifestations of rheumatoid arthritis (RA). High frequency ultrasonography (US) is a sensitive and specific method in diagnosis of CTS. This study is aimed to: firstly assess diameter frequency of CTS in RA with US and compare with a control group; secondly, investigate relationship of CTS with disease activity. One hundred consecutive RA patients (women/men: 78/22) fulfilling ACR 1987 RA criteria and 45 healthy controls (women/control: 34/11) were enrolled into study. Disease activity parameters, RA and CTS patient global assessment and health assessment questionnaire (HAQ-DI) were recorded. Both patient and control group were questioned about secondary causes of CTS, and Katz hand diagram, Boston CTS questionnaire and Phalen ve Tinel tests were applied once for each hand. Wrist joint and carpal tunnel were assessed with US grey scale and power Doppler US, then cross-sectional area of median nerve (CSA) was calculated. Patients with median nerve CSA between 10.0 and 13.0 mm(2) were evaluated with electromyography (EMG). CTS was diagnosed if CSA of median nerve >13.0 mm(2) or CTS was shown with NCS. Although there was no difference between RA patients and controls in age, sex, history of DM (+) and goitre, CTS was more frequent in RA group (respectively, 17.0% vs. 4.4%, P = 0.038). In RA group with CTS, age, history of DM, disease duration, HAQ-DI score, CTS patient global score, Boston symptom severity and functional status scores were elevated compared to without CTS [respectively, 57 (36-73) vs. 50 (24-76), P = 0.041; 35.3% vs. 6.0%, P < 0.001; 108 (12-396) months vs. 72 (6-360) months, P = 0.036; 1.93 (0.75-2.87) vs. 1.125 (0-2.75), P = 0.013; 52 (1-97) vs. 25 (0-91), P = 0.001; 2.81 (1.18-4.17) vs. 2.0 (1.0-4.01), P = 0.01; 3.37 (1.37-5.0) vs. 2.25 (1.0-5.0), P = 0.008]. No difference was found between CTS (+) and (-) RA patients in acute phase reactants, disease activity and US findings

  19. Prevalence and Correlates of Post-traumatic Stress Disorder in Adults With Congenital Heart Disease.

    PubMed

    Deng, Lisa X; Khan, Abigail May; Drajpuch, David; Fuller, Stephanie; Ludmir, Jonathan; Mascio, Christopher E; Partington, Sara L; Qadeer, Ayesha; Tobin, Lynda; Kovacs, Adrienne H; Kim, Yuli Y

    2016-03-01

    Post-traumatic stress disorder (PTSD) is associated with adverse outcomes and increased mortality in cardiac patients. No studies have examined PTSD in the adult congenital heart disease (ACHD) population. The objectives of this study were to assess the prevalence of self-reported symptoms of PTSD in patients with ACHD and explore potential associated factors. Patients were enrolled from an outpatient ACHD clinic and completed several validated measures including the Impact of Event Scale-Revised, PTSD Checklist-Civilian Version, and the Hospital Anxiety and Depression Scale. Clinical data were abstracted through medical data review. A total of 134 participants (mean age 34.6 ± 10.6; 46% men) were enrolled. Of the 127 participants who completed the Impact of Event Scale-Revised, 14 (11%) met criteria for elevated PTSD symptoms specifically related to their congenital heart disease or treatment. Of the 134 patients who completed PTSD Checklist-Civilian Version, 27 (21%) met criteria for global PTSD symptoms. In univariate analyses, patients with congenital heart disease-specific PTSD had their most recent cardiac surgery at an earlier year (p = 0.008), were less likely to have attended college (p = 0.04), had higher rates of stroke or transient ischemic attack (p = 0.03), and reported greater depressive symptoms on the Hospital Anxiety and Depression Scale (7 vs 2, p <0.001). In multivariable analysis, the 2 factors most strongly associated with PTSD were depressive symptoms (p <0.001) and year of most recent cardiac surgery (p <0.03). In conclusion, PTSD is present in 11% to 21% of subjects seen at a tertiary referral center for ACHD. The high prevalence of PTSD in this complex group of patients has important implications for the medical and psychosocial management of this growing population.

  20. Reciprocal Transcriptional Regulation of Metabolic and Signaling Pathways Correlates with Disease Severity in Heart Failure

    PubMed Central

    Barth, Andreas S; Kumordzie, Ami; Frangakis, Constantine; Margulies, Kenneth B; Cappola, Thomas P; Tomaselli, Gordon F

    2012-01-01

    Background Systolic heart failure (HF) is a complex systemic syndrome that can result from a wide variety of clinical conditions and gene mutations. Despite phenotypic similarities, characterized by ventricular dilatation and reduced contractility, the extent of common and divergent gene expression between different forms of HF remains a matter of intense debate. Methods and Results Using a meta-analysis of 28 experimental (mouse, rat, dog) and human HF microarray studies, we demonstrate that gene expression changes are characterized by a coordinated and reciprocal regulation of major metabolic and signaling pathways. In response to a wide variety of stressors in animal models of HF, including ischemia, pressure overload, tachypacing, chronic isoproterenol infusion, Chagas disease, and transgenic mouse models, major metabolic pathways are invariably downregulated, while cell signaling pathways are upregulated. In contrast to this uniform transcriptional pattern observed in experimental animal models which recapitulates a fetal gene expression program, human HF microarray studies displayed a greater heterogeneity, with some studies even showing upregulation of metabolic and downregulation of signaling pathways in end-stage human hearts. These discrepant results between animal and human studies are due to a number of factors, prominently cardiac disease and variable exposure to cold cardioplegic solution in non-failing human samples which can downregulate transcripts involved in oxidative phosphorylation (OXPHOS) within the first 6h, thus mimicking gene expression patterns observed in failing samples. Additionally, beta-blockers and ACE-inhibitor use in end-stage human HF was associated with higher levels of myocardial OXPHOS transcripts, thus partially reversing the fetal gene expression pattern. In human failing samples, downregulation of metabolism was associated with hemodynamic markers of disease severity. Conclusions Irrespective of the etiology, gene

  1. Central core disease. A correlated genetic, histochemical, ultramicroscopic, and biochemical study.

    PubMed Central

    Isaacs, H; Heffron, J J; Badenhorst, M

    1975-01-01

    Two patients suffering from central core disease are presented. The condition is associated with musculoskeletal abnormalities which have been traced back over five generations. In addition to the typical histochemical findings, electronmicroscopic study has revealed the presence of both structured and non-structured cores in adjacent areas. The calcium uptake by the sarcoplasmic reticulum was reduced to one-third of normal. Phosphorylase activity was normal in the one case and reduced to 63% in the other. Actomyosin Mg2+-activated ATPase activity was decreased, as was the Ca2+-dependent ATPase of the sarcoplasmic reticulum. Images PMID:130467

  2. Characterising the grey matter correlates of leukoaraiosis in cerebral small vessel disease

    PubMed Central

    Lambert, Christian; Sam Narean, Janakan; Benjamin, Philip; Zeestraten, Eva; Barrick, Thomas R.; Markus, Hugh S.

    2015-01-01

    Cerebral small vessel disease (SVD) is a heterogeneous group of pathological disorders that affect the small vessels of the brain and are an important cause of cognitive impairment. The ischaemic consequences of this disease can be detected using MRI, and include white matter hyperintensities (WMH), lacunar infarcts and microhaemorrhages. The relationship between SVD disease severity, as defined by WMH volume, in sporadic age-related SVD and cortical thickness has not been well defined. However, regional cortical thickness change would be expected due to associated phenomena such as underlying ischaemic white matter damage, and the observation that widespread cortical thinning is observed in the related genetic condition CADASIL (Righart et al., 2013). Using MRI data, we have developed a semi-automated processing pipeline for the anatomical analysis of individuals with cerebral small vessel disease and applied it cross-sectionally to 121 subjects diagnosed with this condition. Using a novel combined automated white matter lesion segmentation algorithm and lesion repair step, highly accurate warping to a group average template was achieved. The volume of white matter affected by WMH was calculated, and used as a covariate of interest in a voxel-based morphometry and voxel-based cortical thickness analysis. Additionally, Gaussian Process Regression (GPR) was used to assess if the severity of SVD, measured by WMH volume, could be predicted from the morphometry and cortical thickness measures. We found significant (Family Wise Error corrected p < 0.05) volumetric decline with increasing lesion load predominately in the parietal lobes, anterior insula and caudate nuclei bilaterally. Widespread significant cortical thinning was found bilaterally in the dorsolateral prefrontal, parietal and posterio-superior temporal cortices. These represent distinctive patterns of cortical thinning and volumetric reduction compared to ageing effects in the same cohort, which exhibited

  3. Correlation of Immunomodulatory and Therapeutic Activities of Interferon and Interferon Inducers in Metastatic Disease

    DTIC Science & Technology

    1988-01-01

    acid solubilized with poly-L-Iysine in carboxy methyl cellulose (pICLC) in treating metastatic disease was investigated by comparing effector cell...polycytidylic acid, poly(l.C)-LC or pICLC, poly(lC) solubilized with poly-L- lysine in carboxymethyl cellulose . Paul L. Black’s present address is Virology...with poly-L-lysine and solubilized with carboxymethyl cellulose [poly(IC)-LC] alleviates this problem [44,45]. Both recombinant murine interferon-gamma

  4. Pain in Alzheimer's disease: A study of behavior and neural correlates

    NASA Astrophysics Data System (ADS)

    Beach, Paul Anthony

    Alzheimer's disease (AD) is a devastating neurodegenerative disease characterized by insidious and progressive impairment of cognition, emotion, and memory. Though pain in patients with AD is a major medical concern it is under diagnosed and under treated in patients, compared to cognitively healthy elderly. Further complicating matters, subjective self-report of pain by becomes increasingly compromised with disease progression; this often leaves clinicians and caregivers no choice but to rely on discerning pain from behavior alone. Patients also report pain at a lower frequency and intensity than healthy seniors (HS). These findings, coupled with recognition that AD pathology affects many pain processing brain regions, have prompted examination of whether AD alters pain perception. While there is evidence that AD actually predisposes heightened perception of pain, several issues remain: experimental work is limited to a handful of studies, whose results have been inconsistent; few examinations of pain in AD have included patients with advanced disease; the neural mechanism underlying altered pain in AD is not clear. I addressed these gaps in the literature by examining subjective, behavioral, and autonomic pain responses in 33 HS and 38 patients with varying severities of AD. A subset of these subjects (24 HS and 20 AD) were scanned, using fMRI. I then determined how the functional connectivity of various resting-state networks (RSNs) were associated with measured pain responses. I found that AD patients rated low-level stimuli as more painful than HS. Also, patients, regardless of severity, showed greater degrees of pain behaviors than HS - both with respect to global behaviors as measured by a clinical pain scale and facial responses as measured by an experimental tool. In contrast, autonomic responses were blunted with advancing AD. Altered pain responses in AD were associated with altered function of RSNs involved in attention and internal mentation, affect

  5. Characterising the grey matter correlates of leukoaraiosis in cerebral small vessel disease.

    PubMed

    Lambert, Christian; Sam Narean, Janakan; Benjamin, Philip; Zeestraten, Eva; Barrick, Thomas R; Markus, Hugh S

    2015-01-01

    Cerebral small vessel disease (SVD) is a heterogeneous group of pathological disorders that affect the small vessels of the brain and are an important cause of cognitive impairment. The ischaemic consequences of this disease can be detected using MRI, and include white matter hyperintensities (WMH), lacunar infarcts and microhaemorrhages. The relationship between SVD disease severity, as defined by WMH volume, in sporadic age-related SVD and cortical thickness has not been well defined. However, regional cortical thickness change would be expected due to associated phenomena such as underlying ischaemic white matter damage, and the observation that widespread cortical thinning is observed in the related genetic condition CADASIL (Righart et al., 2013). Using MRI data, we have developed a semi-automated processing pipeline for the anatomical analysis of individuals with cerebral small vessel disease and applied it cross-sectionally to 121 subjects diagnosed with this condition. Using a novel combined automated white matter lesion segmentation algorithm and lesion repair step, highly accurate warping to a group average template was achieved. The volume of white matter affected by WMH was calculated, and used as a covariate of interest in a voxel-based morphometry and voxel-based cortical thickness analysis. Additionally, Gaussian Process Regression (GPR) was used to assess if the severity of SVD, measured by WMH volume, could be predicted from the morphometry and cortical thickness measures. We found significant (Family Wise Error corrected p < 0.05) volumetric decline with increasing lesion load predominately in the parietal lobes, anterior insula and caudate nuclei bilaterally. Widespread significant cortical thinning was found bilaterally in the dorsolateral prefrontal, parietal and posterio-superior temporal cortices. These represent distinctive patterns of cortical thinning and volumetric reduction compared to ageing effects in the same cohort, which exhibited

  6. Sleep/wake problems in Parkinson's disease: pathophysiology and clinicopathologic correlations.

    PubMed

    Ondo, William G

    2014-08-01

    In his initial description of shaking palsy, James Parkinson first noted that sleep became disturbed with advancing paralysis agitans. More recent studies have confirmed that the majority of patients with Parkinson's disease (PD) suffer from some sleep disturbances. This can manifest as difficulty in falling or staying asleep, fractionated sleep, specific parasomnias, and daytime sleepiness. In this article, we will explore the pathophysiology of these varied sleep disorders. In most cases, however, the definitive etiology is debated, and phenotypes are often felt to be multifactorial. Some of these may be associated with dopaminergic dysfunction, some presumed to arise from varied non-dopaminergic PD pathology, and some from PD treatments.

  7. Visual dysfunction and its correlation with retinal changes in patients with Parkinson's disease: an observational cross-sectional study

    PubMed Central

    Polo, V; Satue, M; Rodrigo, M J; Otin, S; Alarcia, R; Bambo, M P; Fuertes, M I; Larrosa, J M; Pablo, L E; Garcia-Martin, E

    2016-01-01

    Objectives To evaluate visual dysfunction and its correlation with structural changes in the retina in patients with Parkinson's disease (PD). Methods Patients with PD (n=37) and controls (n=37) were included in an observational cross-sectional study, and underwent visual acuity (VA), colour vision (using the Farnsworth and Lanthony desaturated D15 colour tests) and contrast sensitivity vision (CSV; using the Pelli-Robson chart and CSV 1000E test) evaluation to measure visual dysfunction. Structural measurements of the retinal nerve fibre layer (RNFL), and macular and ganglion cell layer (GCL) thicknesses, were obtained using spectral domain optical coherence tomography (SD-OCT). Comparison of obtained data, and correlation analysis between functional and structural results were performed. Results VA (in all different contrast levels) and all CSV spatial frequencies were significantly worse in patients with PD than in controls. Colour vision was significantly affected based on the Lanthony colour test. Significant GCL loss was observed in the minimum GCL+inner plexiform layer. A clear tendency towards a reduction in several macular sectors (central, outer inferior, outer temporal and superior (inner and outer)) and in the temporal quadrant of the RNFL thickness was observed, although the difference was not significant. CSV was the functional parameter most strongly correlated with structural measurements in PD. Colour vision was associated with most GCL measurements. Macular thickness was strongly correlated with macular volume and functional parameters (r>0.70, p<0.05). Conclusions Patients with PD had visual dysfunction that correlated with structural changes evaluated by SD-OCT. GCL measurements may be reliable indicators of visual impairment in patients with PD. PMID:27154474

  8. Historical Mammal Extinction on Christmas Island (Indian Ocean) Correlates with Introduced Infectious Disease

    PubMed Central

    Wyatt, Kelly B.; Campos, Paula F.; Gilbert, M. Thomas P.; Kolokotronis, Sergios-Orestis; Hynes, Wayne H.; DeSalle, Rob; Daszak, Peter; MacPhee, Ross D. E.; Greenwood, Alex D.

    2008-01-01

    It is now widely accepted that novel infectious disease can be a leading cause of serious population decline and even outright extinction in some invertebrate and vertebrate groups (e.g., amphibians). In the case of mammals, however, there are still no well-corroborated instances of such diseases having caused or significantly contributed to the complete collapse of species. A case in point is the extinction of the endemic Christmas Island rat (Rattus macleari): although it has been argued that its disappearance ca. AD 1900 may have been partly or wholly caused by a pathogenic trypanosome carried by fleas hosted on recently-introduced black rats (Rattus rattus), no decisive evidence for this scenario has ever been adduced. Using ancient DNA methods on samples from museum specimens of these rodents collected during the extinction window (AD 1888–1908), we were able to resolve unambiguously sequence evidence of murid trypanosomes in both endemic and invasive rats. Importantly, endemic rats collected prior to the introduction of black rats were devoid of trypanosome signal. Hybridization between endemic and black rats was also previously hypothesized, but we found no evidence of this in examined specimens, and conclude that hybridization cannot account for the disappearance of the endemic species. This is the first molecular evidence for a pathogen emerging in a naïve mammal species immediately prior to its final collapse. PMID:18985148

  9. A correlation of pregnancy term, disease activity, serum female hormones, and cytokines in uveitis

    PubMed Central

    Chan, C-C; Reed, G F; Kim, Y; Agrón, E; Buggage, R R

    2004-01-01

    Background/aims: Pregnancy and the postpartum period are associated with the activity of autoimmune diseases including uveitis. Although the exact mechanism is unknown, hormones are reported to alter inflammatory cytokines and influence disease activity. The authors studied ocular inflammation, female hormones, and serum cytokine levels during and after pregnancy. Methods: A prospective, observational case study was conducted. Four pregnant women in their first trimester with chronic non-infectious uveitis were followed monthly until 6 months after delivery. Serum female hormones (oestrogen, progesterone, prolactin) and various cytokines (IL-2, IL-4, IL-5, IL-6, IL-10, IFN-γ, and TGF-β) were measured by ELISA. Results: The four patients had five full term pregnancies. Uveitis activity decreased after the first trimester but flared in the early postpartum period. Serum female hormones, highly elevated during pregnancy, drastically dropped post partum. Cytokine levels except TGF-β were mostly undetectable. Conclusion: Female hormones and TGF-β may contribute to the activity of uveitis during pregnancy and the postpartum period. PMID:15548800

  10. Prevalence and correlates of coronary heart disease: first population-based study in Lebanon

    PubMed Central

    Zeidan, Rouba Karen; Farah, Rita; Chahine, Mirna N; Asmar, Roland; Hosseini, Hassan; Salameh, Pascale; Pathak, Atul

    2016-01-01

    Background Lebanon is experiencing a growing epidemic of coronary heart diseases (CHDs), as most low- and middle-income countries currently are. However, this growth can be attenuated if effective preventive strategies are adopted. Purpose To provide the first national population-based prevalence of CHD and to describe the profile of Lebanese adults with prevalent CHD. Methods We carried out a cross-sectional study using a multistage cluster sample across Lebanon. We interviewed residents aged 40 years and older using a questionnaire that captured the presence of CHDs and their risk factors (RFs). Results Our study showed that 13.4% of the Lebanese population aged ≥40 years suffer from a prevalent CHD. CHD seemed to appear more prematurely than in developed countries, and males seemed to be more subject to CHD than females until a certain age. CHD was associated with older age, male sex, a lower economic situation, hypercholesterolemia, hypertension, having a family history of premature cardiovascular diseases, and suffering from diabetes. However, smoking and waist circumference did not seem to have an independent effect on CHD, but rather an effect mediated by biological RFs. Conclusion This is the first nationwide endeavor conducted in Lebanon to assess the prevalence of CHD. This study also confirms the relevance of the classic RFs of CHD and their applicability to the Lebanese population, thus allowing for prevention strategies. PMID:27051290

  11. Hepatic angiosarcoma mimicking sinusoidal obstruction syndrome/venoocclusive disease: a pathologic-radiologic correlation.

    PubMed

    Wiland, Homer O; Pai, Rish K; Purysko, Andrei S

    2012-08-01

    We present a case of a 63-year-old man with liver dysfunction and biopsy findings of venoocclusive disease (VOD) who, at autopsy, was discovered to have multifocal hepatic angiosarcoma. After double lung transplantation, he initially presented with signs of liver failure and portal hypertension resulting in recurrent high-volume ascites. Clinically, VOD was considered, and tacrolimus was discontinued, due to its known association with VOD. This, however, did not result in clinical improvement, and computed tomography eventually revealed the development of multiple low-attenuating hepatic lesions over the course of several months. Biopsies of the masses and background liver demonstrated changes most consistent with VOD, characterized by sinusoidal congestion affecting the centrilobular areas with associated hepatocyte atrophy and dropout. A reticulin stain highlighted deposition of reticulin fibers within the sinusoids and central veins. Scattered sinusoidal atypical cells were identified; however, a definitive diagnosis of malignancy was not possible. He eventually passed away because of complications of liver disease. At autopsy, there were multiple firm, red-brown masses identified throughout both hepatic lobes. Upon histologic review, the masses were shown to be angiosarcoma. Away from the tumor, the liver also demonstrated features of VOD. It is likely that the histologic appearance of VOD in the background liver probably represents secondary changes due to injury to the hepatic sinusoids by the primary malignancy. We conclude that it is necessary to consider the possibility of unsampled vascular malignancy when hepatic masses are identified on imaging and histology is consistent with VOD.

  12. The Prevalence and Extent of Gastroesophageal Reflux Disease Correlates to the Type of Lung Transplantation

    PubMed Central

    Fisichella, Piero Marco; Davis, Christopher S.; Shankaran, Vidya; Gagermeier, James; Dilling, Daniel; Alex, Charles G.; Kovacs, Elizabeth J.; Joehl, Raymond J.; Love, Robert B.

    2013-01-01

    Background Evidence is increasingly convincing that lung transplantation is a risk factor of gastroesophageal reflux disease (GERD). However, it is still not known if the type of lung transplant (unilateral, bilateral, or retransplant) plays a role in the pathogenesis of GERD. Study Design The records of 61 lung transplant patients who underwent esophageal function tests between September 2008 and May 2010, were retrospectively reviewed. These patients were divided into 3 groups based on the type of lung transplant they received: unilateral (n=25); bilateral (n=30), and retransplant (n=6). Among these groups we compared: (1) the demographic characteristics (eg, sex, age, race, and body mass index); (2) the presence of Barrett esophagus, delayed gastric emptying, and hiatal hernia; and (3) the esophageal manometric and pH-metric profile. Results Distal and proximal reflux were more prevalent in patients with bilateral transplant or retransplant and less prevalent in patients after unilateral transplant, regardless of the cause of their lung disease. The prevalence of hiatal hernia, Barrett esophagus, and the manometric profile were similar in all groups of patients. Conclusions Although our data show a discrepancy in prevalence of GERD in patients with different types of lung transplantation, we cannot determine the exact cause for these findings from this study. We speculate that the extent of dissection during the transplant places the patients at risk for GERD. On the basis of the results of this study, a higher level of suspicion of GERD should be held in patients after bilateral or retransplantation. PMID:22318059

  13. ALS patients' regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity.

    PubMed

    Beers, David R; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R; Alsuliman, Abdullah S; Shpall, Elizabeth J; Rezvani, Katy; Appel, Stanley H

    2017-03-09

    Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression.

  14. ALS patients’ regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity

    PubMed Central

    Beers, David R.; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R.; Alsuliman, Abdullah S.; Shpall, Elizabeth J.; Rezvani, Katy

    2017-01-01

    Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression. PMID:28289705

  15. Strong Expression of Chemokine Receptor CXCR4 by Renal Cell Carcinoma Correlates with Advanced Disease

    PubMed Central

    Wehler, Thomas C.; Graf, Claudine; Biesterfeld, Stefan; Brenner, Walburgis; Schadt, Jörg; Gockel, Ines; Berger, Martin R.; Thüroff, Joachim W.; Galle, Peter R.; Moehler, Markus; Schimanski, Carl C.

    2008-01-01

    Diverse chemokines and their receptors have been associated with tumor growth, tumor dissemination, and local immune escape. In different tumor entities, the level of chemokine receptor CXCR4 expression has been linked with tumor progression and decreased survival. The aim of this study was to evaluate the influence of CXCR4 expression on the progression of human renal cell carcinoma. CXCR4 expression of renal cell carcinoma was assessed by immunohistochemistry in 113 patients. Intensity of CXCR4 expression was correlated with both tumor and patient characteristics. Human renal cell carcinoma revealed variable intensities of CXCR4 expression. Strong CXCR4 expression of renal cell carcinoma was significantly associated with advanced T-status (P = .039), tumor dedifferentiation (P = .0005), and low hemoglobin (P = .039). In summary, strong CXCR4 expression was significantly associated with advanced dedifferentiated renal cell carcinoma. PMID:19266088

  16. Correlation between the Movement Disorders Society Unified Parkinson's Disease rating scale (MDS-UPDRS) and the Unified Parkinson's Disease rating scale (UPDRS) during L-dopa acute challenge.

    PubMed

    Merello, Marcelo; Gerschcovich, Eliana Roldan; Ballesteros, Diego; Cerquetti, Daniel

    2011-11-01

    While Movement Disorders Society Unified Parkinson's Disease rating scale (MDS-UPDRS) validation has been exhaustive; performance evaluation to detect acute changes arising after administration of a single dose of L-dopa has yet to be explored. To determine the correlation between UPDRS and MDS-UPDRS during the acute challenge with Ldopa and the MDS-UPDRS equivalent to 30% cutoff score of UPDRS for defining responsiveness, 64 patients were assessed. Consecutive assessments were performed immediately before and after administration of a single dose of L-dopa/carbidopa 250/25 mg using the motor section of the UPDRS and the MDS-UPDRS. Good diagnostic accuracy, consistent with published findings of high correlation between scales was observed. Area under the curve (AUC) was 0.99 (CI = 0.97-1.00, P < 0.001) and maximum Youden index (Y = 0.905) corresponded to a cutoff of 24.5%. In conclusion we have found an excellent correlation between UPDRS and MDS-UPDRS and that the 30% of variation in UPDRS score used for predicting sustained long term L-dopa response was equivalent to 24% in MDS-UPDRS.

  17. Yeast Cells Expressing the Human Mitochondrial DNA Polymerase Reveal Correlations between Polymerase Fidelity and Human Disease Progression*

    PubMed Central

    Qian, Yufeng; Kachroo, Aashiq H.; Yellman, Christopher M.; Marcotte, Edward M.; Johnson, Kenneth A.

    2014-01-01

    Mutations in the human mitochondrial polymerase (polymerase-γ (Pol-γ)) are associated with various mitochondrial disorders, including mitochondrial DNA (mtDNA) depletion syndrome, Alpers syndrome, and progressive external opthamalplegia. To correlate biochemically quantifiable defects resulting from point mutations in Pol-γ with their physiological consequences, we created “humanized” yeast, replacing the yeast mtDNA polymerase (MIP1) with human Pol-γ. Despite differences in the replication and repair mechanism, we show that the human polymerase efficiently complements the yeast mip1 knockouts, suggesting common fundamental mechanisms of replication and conserved interactions between the human polymerase and other components of the replisome. We also examined the effects of four disease-related point mutations (S305R, H932Y, Y951N, and Y955C) and an exonuclease-deficient mutant (D198A/E200A). In haploid cells, each mutant results in rapid mtDNA depletion, increased mutation frequency, and mitochondrial dysfunction. Mutation frequencies measured in vivo equal those measured with purified enzyme in vitro. In heterozygous diploid cells, wild-type Pol-γ suppresses mutation-associated growth defects, but continuous growth eventually leads to aerobic respiration defects, reduced mtDNA content, and depolarized mitochondrial membranes. The severity of the Pol-γ mutant phenotype in heterozygous diploid humanized yeast correlates with the approximate age of disease onset and the severity of symptoms observed in humans. PMID:24398692

  18. 13C-methacetin breath test correlates with clinical indices of liver disease severity in patients with primary biliary cirrhosis.

    PubMed

    Kochel-Jankowska, A; Hartleb, M; Jonderko, K; Kaminska, M; Kasicka-Jonderko, A

    2013-02-01

    This prospective study intended to ascertain if cytochrome P450 dependent liver function is affected in early and late histological stages of primary biliary cirrhosis (PBC). The study included 32 female PBC patients (mean age 55.4 years, range 33-70) and 16 aged-matched healthy women (mean age 52.6 years, range 38-65). In every subject a 13(C)-methacetin breath test (13(C)-MBT) was applied, and the results were related to histological Ludwig's staging system and several indices of liver disease severity comprising the MAYO-1, MAYO-2, MELD, and Child-Pugh score. The 13(C)-MBT differentiated healthy controls from the patients with Ludwig IV and Ludwig III histopathological stages of PBC. The most significant relationships (i.e. explaining >50% of the variance) were found between measurements of the momentary breath 13(C) elimination from 6 to 18 minutes as well as the 15-min or 30-min cumulative elimination and the MAYO-1 or MAYO-2 scores. The breath test poorly correlated with histopathological features of PBC, however, it accurately discriminated cirrhotic from non-cirrhotic patients (momentary breath 13(C) elimination at 40 min, AUROC 0,958). In conclusion, 13(C)-MBT correlates with clinical scoring systems, especially those specifically designed for PBC (Mayo model) and accurately recognizes the disease at the stage of cirrhosis up to 40 minutes of the test duration.

  19. The Expression of NOX4 in Smooth Muscles of Small Airway Correlates with the Disease Severity of COPD

    PubMed Central

    2016-01-01

    Airway smooth muscle (ASM) remodeling is a hallmark in chronic obstructive pulmonary disease (COPD), and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases (NOXs) produced reactive oxygen species (ROS) play a crucial role in COPD pathogenesis. In the present study, the expression of NOX4 and its correlation with the ASM hypertrophy/hyperplasia, clinical pulmonary functions, and the expression of transforming growth factor β (TGF-β) in the ASM of COPD small airways were investigated by semiquantitative morphological and/or immunohistochemistry staining methods. The results showed that an elevated expression of NOX4 and TGF-β, along with an increased volume of ASM mass, was found in the ASM of small airways in COPD patients. The abundance of NOX4 protein in the ASM was increased with disease severity and inversely correlated with the pulmonary functions in COPD patients. In addition, the expression of NOX4 and ASM marker α-SMA was colocalized, and the increased NOX4 expression was found to accompany an upregulated expression of TGF-β in the ASM of small airways of COPD lung. These results indicate that NOX4 may be a key regulator in ASM remodeling of small airway, in part through a mechanism interacting with TGF-β signaling in the pathogenesis of COPD, which warrants further investigation. PMID:27656649

  20. Subthalamic nucleus stimulation-induced regional blood flow responses correlate with improvement of motor signs in Parkinson disease.

    PubMed

    Karimi, M; Golchin, N; Tabbal, S D; Hershey, T; Videen, T O; Wu, J; Usche, J W M; Revilla, F J; Hartlein, J M; Wernle, A R; Mink, J W; Perlmutter, J S

    2008-10-01

    Deep brain stimulation of the subthalamic nucleus (STN DBS) improves motor symptoms in idiopathic Parkinson's disease, yet the mechanism of action remains unclear. Previous studies indicate that STN DBS increases regional cerebral blood flow (rCBF) in immediate downstream targets but does not reveal which brain regions may have functional changes associated with improved motor manifestations. We studied 48 patients with STN DBS who withheld medication overnight and underwent PET scans to measure rCBF responses to bilateral STN DBS. PET scans were performed with bilateral DBS OFF and ON in a counterbalanced order followed by clinical ratings of motor manifestations using Unified Parkinson Disease Rating Scale 3 (UPDRS 3). We investigated whether improvement in UPDRS 3 scores in rigidity, bradykinesia, postural stability and gait correlate with rCBF responses in a priori determined regions. These regions were selected based on a previous study showing significant STN DBS-induced rCBF change in the thalamus, midbrain and supplementary motor area (SMA). We also chose the pedunculopontine nucleus region (PPN) due to mounting evidence of its involvement in locomotion. In the current study, bilateral STN DBS improved rigidity (62%), bradykinesia (44%), gait (49%) and postural stability (56%) (paired t-tests: P < 0.001). As expected, bilateral STN DBS also increased rCBF in the bilateral thalami, right midbrain, and decreased rCBF in the right premotor cortex (P < 0.05, corrected). There were significant correlations between improvement of rigidity and decreased rCBF in the SMA (r(s) = -0.4, P < 0.02) and between improvement in bradykinesia and increased rCBF in the thalamus (r(s) = 0.31, P < 0.05). In addition, improved postural reflexes correlated with decreased rCBF in the PPN (r(s) = -0.38, P < 0.03). These modest correlations between selective motor manifestations and rCBF in specific regions suggest possible regional selectivity for improvement of different motor

  1. Towards identification of immune and genetic correlates of severe influenza disease in Indigenous Australians.

    PubMed

    Clemens, E Bridie; Grant, Emma J; Wang, Zhongfang; Gras, Stephanie; Tipping, Peta; Rossjohn, Jamie; Miller, Adrian; Tong, Steven Y C; Kedzierska, Katherine

    2016-04-01

    Indigenous populations, including Indigenous Australians, are highly susceptible to severe influenza disease and the underlying mechanisms are unknown. We studied immune and genetic factors that could predicate severe influenza disease in Indigenous Australians enrolled in the LIFT study: looking into influenza T-cell immunity. To examine CD8(+) T-cell immunity, we characterised human leukocyte antigen (HLA) profiles. HLA typing confirmed previous studies showing predominant usage of HLA-A*02:01, 11:01, 24:02, 34:01 and HLA-B*13:01, 15:21, 40:01/02, 56:01/02 in Indigenous Australians. We identified two new HLA alleles (HLA-A*02:new and HLA-B*56:new). Modelling suggests that variations within HLA-A*02:new (but not HLA-B56:new) could affect peptide binding. There is a relative lack of known influenza epitopes for the majority of these HLAs, with the exception of a universal HLA-A*02:01-M158 epitope and proposed epitopes presented by HLA-A*11:01/HLA-A*24:02. To dissect universal CD8(+) T-cell responses, we analysed the magnitude, function and T-cell receptor (TCR) clonality of HLA-A*02:01-M158(+)CD8(+) T cells. We found comparable IFN-γ, TNF and CD107a and TCRαβ characteristics in Indigenous and non-Indigenous Australians, suggesting that the ~15% of Indigenous people that express HLA-A*02:01 have universal influenza-specific CD8(+) T-cell immunity. Furthermore, the frequency of an influenza host risk factor, IFITM3-C/C, was comparable between Indigenous Australians and Europeans, suggesting that expression of this allele does not explain increased disease severity at a population level. Our study indicates a need to identify novel influenza-specific CD8(+) T-cell epitopes restricted by HLA-A and HLA-B alleles prevalent in Indigenous populations for the rational design of universal T-cell vaccines.

  2. Physiopathology of Chagas' heart disease: correlations between clinical and experimental findings*

    PubMed Central

    Anselmi, Alfonso; Moleiro, Federico

    1971-01-01

    In penetrating the heart and developing in it, Trypanosoma cruzi produces an immunoallergic reaction that leads to changes in the histological structure of the myocardium; these changes alter the fundamental properties of the heart, causing fundamental dynamic disorders and morphological changes in the organ. In Chagas' cardiomyopathy, the velocity of impulse propagation diminishes in the auricular and ventricular musculature, altering the activation mechanism, this being shown by changes in the P-wave and in ventricular focal blocks. The functional refractory period (FRP) is shortened in the auricular and ventricular tissue and constitutes, together with changes in conductivity, the physiopathological basis that explains the circus movement—the fundamental factor of the arrhythmias of this stage of the disease. Localization of the inflammation in the A-V conduction system increases the duration of the FRP, producing all types of A-V block. The oedema and the cellular interstitial infiltration seen during this acute phase reduce the distensibility of the fibres; this, in turn, limits their contractility, producing a decrease in systolic volume and an increase in the final diastolic pressure in the chambers of the heart—fundamental factors in reducing kinesia and in increasing the heart's volume. In the chronic phase, destruction of the contractile tissue and fibroblastic proliferation bring into play compensatory mechanisms that maintain the strength of cardiac contractions; the elongation of the fibres and the nature of the dynamic pressure—volume curves explain the dilatation of the chambers of the heart and the dynamic changes seen in this phase of the disease. PMID:5003721

  3. Radionuclide brain imaging correlates of cognitive impairment in Parkinson's disease (PD).

    PubMed

    Nobili, Flavio; Morbelli, Silvia; Arnaldi, Dario; Ferrara, Michela; Campus, Claudio; Brugnolo, Andrea; Mazzei, Debora; Mehrdad, Naseri; Sambuceti, Gianmario; Rodriguez, Guido

    2011-11-15

    A subtle cognitive impairment can be detected early in the course of Parkinson's disease (PD). Executive, memory and visuospatial functions are specifically affected, but the underlying pathophysiological basis is not well elucidated yet and may be heterogeneous. The recent identification of a PD-related cognitive metabolic pattern (PDCP), including hypometabolism in associative frontal, parietal and posterior limbic structures, has integrated the classical notion of a striato-frontal syndrome at the basis of cognitive dys-function. Recent evidence suggests that whilst executive dys-function is seen in virtually all PD patients, visuospatial and memory impairment may share a higher risk for the subsequent development of dementia. By means of perfusion SPECT and [18F]FDG-PET, cortical dys-function may be highlighted since the early stages, it is more evident in PD patients with Mild Cognitive Impairment (MCI), and reaches the maximum in PD dementia (PDD). Posterior temporo-parieto-occipital dys-function in associative and limbic cortex, closely resembling that found in Alzheimer's disease patients, is found in PDD, with a more severe occipital hypometabolism and a relatively milder hypometabolism in medial temporal lobe structures. Furthermore, deficit of acetylcholinesterase (AchE) can be found by means of [11C]MP4A-PET already in early stage of PD, especially in posterior regions, then becoming more severe in PDD and in dementia with Lewy bodies (DLB). Administration of AchE inhibitors to PDD patients increased brain metabolism in bilateral frontal and left parietal regions, and left posterior cingulate. Finally, the recent availability of radiopharmaceuticals able to disclose amyloid brain deposition has allowed to demonstrate amyloid load in a part of patients with PDD, possibly due to diffuse rather than neuritic plaques. Brain PET and SPECT have strongly contributed to the understanding of the pathophysiology of cognitive impairment in PD and may serve as

  4. Elevated level of HSPA1L mRNA correlates with graft-versus-host disease.

    PubMed

    Atarod, Sadaf; Turner, Brie; Pearce, Kim Frances; Ahmed, Shaheda S; Norden, Jean; Bogunia-Kubik, Katarzyna; Wang, Xiao-nong; Collin, Matthew; Dickinson, Anne Mary

    2015-06-01

    Graft-versus-host disease (GVHD) can be a fatal complication of allogeneic stem cell transplantation (allo-HSCT). GVHD can be classified as acute (aGVHD: up to 100 days) or chronic (cGVHD: after 100 days) based on the time-point of disease occurrence. At present there are a limited number of biomarkers available for use in the clinic. Thus, the aim of this research was to evaluate the biomarker potential of the extensively studied Heat Shock Protein 70 family members (HSPA1A/HSPA1B and HSPA1L) at the messenger RNA (mRNA) level in acute and cGVHD patient cohorts. In the skin biopsies, HSPA1L mRNA expression was lower in patients with severe aGVHD (grades II-III) when compared to those with none or low grade aGVHD (grades 0-I) and normal controls. In whole blood, HSPA1L mRNA expression level was significantly (p = 0.008) up-regulated at 28 days post-transplant in cGVHD patients with a significant area under the curve (AUC = 0.773). In addition, HSPA1B expression in whole blood was significantly higher at 3 months post-transplant in both the aGVHD grade II-III (p = 0.012) and cGVHD (p = 0.027) patients. Our initial results in this small cohort show that quantifying HSPA1L mRNA expression in the whole blood of allo-HSCT patients at day 28 post-allo-HSCT may be a useful predictive biomarker for cGVHD.

  5. Clinicopathological correlates of chronic kidney disease of unknown etiology in Sri Lanka

    PubMed Central

    Selvarajah, M.; Weeratunga, P.; Sivayoganthan, S.; Rathnatunga, N.; Rajapakse, S.

    2016-01-01

    Chronic kidney disease of unknown etiology (CKDu) is a major healthcare issue in Sri Lanka. This study included 125 consecutive patients with a diagnosis of CKDu undergoing renal biopsy at one hospital from 2008 to 2012. Associations between renal outcome parameters, epidemiological data, and histopathological findings were examined and regression models constructed based on univariate associations with outcome variables as serum creatinine >1.2 and stage of CKD >3. The mean patient age was 46.21 years (standard deviation = 11.64). A marked male predominance was noted. A positive family history of CKD was seen in 35.8%. Prominent histopathological features were glomerular sclerosis (94.8%), interstitial infiltration (76%) with lymphocytic infiltration, interstitial fibrosis (71.2%), and tubular atrophy (70.4%). Importantly, significant histological changes were seen in patients with early CKDu. For CKD stage >3 independent associations were: interstitial fibrosis [P = 0.005; odds ratio (OR) =0.153] and interstitial infiltrate (P = 0.030; OR = 0.2440. For serum creatinine >1.2, independent predictors were >50% glomerular sclerosis (P = 0.041; OR = 0.92), tubular atrophy (P = 0.034; OR = 0.171, and more than 40 residential life years (P = 0.009; OR = 9.229). Chronic tubulointerstitial nephritis (TIN) appears to be the predominant histopathological finding in patients with CKDu, with significant renal pathology established early on in the course of the disease. Interstitial infiltration appears to be an independent association of advancing CKD, CKDu, histopathology, histology, and TIN. PMID:27795631

  6. Childhood overweight-obesity and periodontal diseases: is there a real correlation?

    PubMed Central

    Sfasciotti, Gian Luca; Marini, Roberta; Pacifici, Andrea; Ierardo, Gaetano; Pacifici, Luciano; Polimeni, Antonella

    2016-01-01

    Summary Objective The association between obesity and periodontitis has been extensively investigated in adults but not in young people. The aim of this study was to examine the association between overweight-obesity and periodontal disease in pediatric subjects. Methods Controlled cross-sectional study involving 100 school children of both gender (50 M and 50 F) between 7 and 12 years of age (mean age 9,19±1,57). Two groups were formed based on Body Mass Index value: test group with BMI ≥ 25 Kg/m2 and control group with BMI ≤ 24 Kg/m2. Diet intake and oral hygiene habits were recorded by a specific questionnaire and the periodontal clinical parameters were evaluated. Results The periodontal examination in the control group revealed a full-mouth plaque score (FMPS) value equal to 21.86% against 50.08% in the group of patients overweight/obese; the full-mouth bleeding score (FMBS) in the control group amounted to 12.7% against 26.24% of test group. No patient in either group included in the study presented a probing pocket depth (PPD) ≥3, so a significant difference regarding this value was not found. Regarding the frequency and quantity of food consumption, the number of obese patients who did not follow a balanced diet largely exceeded the number of normal-weight patients (70 versus 20%). Conclusions These results focus the attention on the negative impact of obesity on gingival health in young subjects, probably due to a combination of metabolic and inflammatory profiles and the result of a careless attitude towards prevention diseases of the oral cavity. PMID:28149453

  7. Studies on the correlation with olfactory dysfunction in a transgenic mice model of Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Rasheed, Ameer; Lee, Ji Hye; Suh, Yoo-Hun; Moon, Cheil

    2013-05-01

    Alzheimer's disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the presence of proteinaceous deposits in the brain. AD often results in olfactory dysfunction and impaired olfactory perceptual acuity may be a potential biomarker for early diagnosis of AD. Until recently, there is no Alzheimer's nanoscope or any other high-end microscope developed to be capable of seeing buried feature of AD clearly. Modern neuroimaging techniques are more effective only after the occurrence of cognitive impairment. Therefore, early detection of Alzheimer's disease is critical in developing effective treatment of AD. H and E (Haematoxyline and Eosin) staining is performed for examining gross morphological changes, while TUNEL (transferase (TdT)-mediated dUTP nick end labeling) staining for monitoring neuronal death in the olfactory epithelium (OE). Furthermore, immunohistochemistry and western blot are performed to examine β-amyloid protein expression. AD model animals were Tg2576 (transgenic mice that overexpress a mutated form of the Aβ precursor protein), and 6 month (before onset of AD symptoms) and 14 month (after onset of AD symptoms) old WT (wild type) and transgenic mice were compared in their olfactory system. We found that in OE of Tg2576 mice, thickness and total number of cells were decreased, while the numbers of TUNEL-positive neurons, caspase-3 activation were significantly increased compared with age-matched WT. Our results demonstrate that the olfactory system may get deteriorated before onset of AD symptoms. Our findings imply that an olfactory biopsy could be served as an early and relatively simple diagnostic tool for potential AD patients.

  8. National Institutes of Health chronic graft-versus-host disease staging in severely affected patients: organ and global scoring correlate with established indicators of disease severity and prognosis.

    PubMed

    Baird, Kristin; Steinberg, Seth M; Grkovic, Lana; Pulanic, Drazen; Cowen, Edward W; Mitchell, Sandra A; Williams, Kirsten M; Datiles, Manuel B; Bishop, Rachel; Bassim, Carol W; Mays, Jacqueline W; Edwards, Dean; Cole, Kristen; Avila, Daniele N; Taylor, Tiffany; Urban, Amanda; Joe, Galen O; Comis, Leora E; Berger, Ann; Stratton, Pamela; Zhang, Dan; Shelhamer, James H; Gea-Banacloche, Juan C; Sportes, Claude; Fowler, Daniel H; Gress, Ronald E; Pavletic, Steven Z

    2013-04-01

    Between 2004 and 2010, 189 adult patients were enrolled on the National Cancer Institute's cross-sectional chronic graft-versus-host disease (cGVHD) natural history study. Patients were evaluated by multiple disease scales and outcome measures, including the 2005 National Institutes of Health (NIH) Consensus Project cGVHD severity scores. The purpose of this study was to assess the validity of the NIH scoring variables as determinants of disease severity in severely affected patients in efforts to standardize clinician evaluation and staging of cGVHD. Out of 189 patients enrolled, 125 met the criteria for severe cGVHD on the NIH global score, 62 of whom had moderate disease, with a median of 4 (range, 1-8) involved organs. Clinician-assigned average NIH organ score and the corresponding organ scores assigned by subspecialists were highly correlated (r = 0.64). NIH global severity scores showed significant associations with nearly all functional and quality of life outcome measures, including the Lee Symptom Scale, Short Form-36 Physical Component Scale, 2-minute walk, grip strength, range of motion, and Human Activity Profile. Joint/fascia, skin, and lung involvement affected function and quality of life most significantly and showed the greatest correlation with outcome measures. The final Cox model with factors jointly predictive for survival included the time from cGVHD diagnosis (>49 versus ≤49 months, hazard ratio [HR] = 0.23; P = .0011), absolute eosinophil count at the time of NIH evaluation (0-0.5 versus >0.5 cells/μL, HR = 3.95; P = .0006), and NIH lung score (3 versus 0-2, HR = 11.02; P < .0001). These results demonstrate that NIH organs and global severity scores are reliable measures of cGVHD disease burden. The strong association with subspecialist evaluation suggests that NIH organ and global severity scores are appropriate for clinical and research assessments, and may serve as a surrogate for more complex subspecialist examinations. In this

  9. Correlation between Patient-Reported Symptoms and Ankle-Brachial Index after Revascularization for Peripheral Arterial Disease

    PubMed Central

    Je, Hyung Gon; Kim, Bo Hyun; Cho, Kyoung Im; Jang, Jae Sik; Park, Yong Hyun; Spertus, John

    2015-01-01

    Improvement in quality of life (QoL) is a primary treatment goal for patients with peripheral arterial disease (PAD). The current study aimed to quantify improvement in the health status of PAD patients following peripheral revascularization using the peripheral artery questionnaire (PAQ) and ankle-brachial index (ABI), and to evaluate possible correlation between the two methods. The PAQ and ABI were assessed in 149 symptomatic PAD patients before, and three months after peripheral revascularization. Mean PAQ summary scores improved significantly three months after revascularization (+49.3 ± 15 points, p < 0.001). PAQ scores relating to patient symptoms showed the largest improvement following revascularization. The smallest increases were seen in reported treatment satisfaction (all p’s < 0.001). As expected the ABI of treated limbs showed significant improvement post-revascularization (p < 0.001). ABI after revascularization correlated with patient-reported changes in the physical function and QoL domains of the PAQ. Twenty-two percent of PAD patients were identified as having a poor response to revascularization (increase in ABI < 0.15). Interestingly, poor responders reported improvement in symptoms on the PAQ, although this was less marked than in patients with an increase in ABI > 0.15 following revascularization. In conclusion, data from the current study suggest a significant correlation between improvement in patient-reported outcomes assessed by PAQ and ABI in symptomatic PAD patients undergoing peripheral revascularization. PMID:25993299

  10. Correlated responses of respiratory disease and immune capacity traits of Landrace pigs selected for Mycoplasmal pneumonia of swine (MPS) lesion.

    PubMed

    Okamura, Toshihiro; Maeda, Kouki; Onodera, Wataru; Kadowaki, Hiroshi; Kojima-Shibata, Chihiro; Suzuki, Eisaku; Uenishi, Hirohide; Satoh, Masahiro; Suzuki, Keiichi

    2016-09-01

    Five generations of Landrace pigs selected for average daily gain, backfat thickness, Mycoplasmal pneumonia of swine (MPS) lesion score, and plasma cortisol levels, was executed to decrease the MPS lesion score. Genetic parameters and correlated genetic responses for respiratory disease and peripheral blood immune traits were estimated in 1395 Landrace pigs. We estimated the negative genetic correlation of MPS lesion score with phagocytic activity (PA) at 7 weeks of age (-0.67). The breeding values of PA at 7 weeks of age and 105 kg body weight and the correlated selection response of the ratio of granular leukocytes to lymphocytes at 105 kg body weight were significantly increased, and sheep red blood cell-specific antibody production (AP) was significantly decreased in a selection-dependent manner. Increasing of natural immunological indicators (e.g. PA) and decreasing of humoral immunological indicator (e.g. AP) were observed due to genetically decreasing MPS lesion score.

  11. Striatal Atrophy in the Behavioural Variant of Frontotemporal Dementia: Correlation with Diagnosis, Negative Symptoms and Disease Severity

    PubMed Central

    Walterfang, Mark; Vestberg, Susanna; Velakoulis, Dennis; Wilkes, Fiona A.; Nilsson, Christer; van Westen, Danielle; Looi, Jeffrey C. L.; Santillo, Alexander Frizell

    2015-01-01

    Introduction Behavioural variant frontotemporal dementia (bvFTD) is associated with changes in dorsal striatal parts of the basal ganglia (caudate nucleus and putamen), related to dysfunction in the cortico-striato-thalamic circuits which help mediate executive and motor functions. We aimed to determine whether the size and shape of striatal structures correlated with diagnosis of bvFTD, and measures of clinical severity, behaviour and cognition. Materials and Methods Magnetic resonance imaging scans from 28 patients with bvFTD and 26 healthy controls were manually traced using image analysis software (ITK-SNAP). The resulting 3-D objects underwent volumetric analysis and shape analysis, through spherical harmonic description with point distribution models (SPHARM-PDM). Correlations with size and shape were sought with clinical measures in the bvTFD group, including Frontal Behavioural Inventory, Clinical Dementia Rating for bvFTD, Color Word Interference, Hayling part B and Brixton tests, and Trail-Making Test. Results Caudate nuclei and putamina were significantly smaller in the bvFTD group compared to controls (left caudate 16% smaller, partial eta squared 0.173, p=0.003; right caudate 11% smaller, partial eta squared 0.103, p=0.023; left putamen 18% smaller, partial eta squared 0.179, p=0.002; right putamen 12% smaller, partial eta squared 0.081, p=0.045), with global shape deflation in the caudate bilaterally but no localised shape change in putamen. In the bvFTD group, shape deflations on the left, corresponding to afferent connections from dorsolateral prefrontal mediofrontal/anterior cingulate and orbitofrontal cortex, correlated with worsening disease severity. Global shape deflation in the putamen correlated with Frontal Behavioural Inventory scores—higher scoring on negative symptoms was associated with the left putamen, while positive symptoms were associated with the right. Other cognitive tests had poor completion rates. Conclusion Behavioural

  12. Lung ultrasound in systemic sclerosis: correlation with high-resolution computed tomography, pulmonary function tests and clinical variables of disease.

    PubMed

    Gigante, Antonietta; Rossi Fanelli, Filippo; Lucci, Silvio; Barilaro, Giuseppe; Quarta, Silvia; Barbano, Biagio; Giovannetti, Antonello; Amoroso, Antonio; Rosato, Edoardo

    2016-03-01

    Interstitial lung disease (ILD) is a hallmark of systemic sclerosis (SSc). Although high-resolution computed tomography (HRCT) is the gold standard to diagnose ILD, recently lung ultrasound (LUS) has emerged in SSc patients as a new promising technique for the ILD evaluation, noninvasive and radiation-free. The aim of this study was to evaluate if there is a correlation between LUS, chest HRCT, pulmonary function tests findings and clinical variables of the disease. Thirty-nine patients (33 women and 6 men; mean age 51 ± 15.2 years) underwent clinical examination, HRCT, pulmonary function tests and LUS for detection of B-lines. A positive correlation exists between the number of B-lines and the HRCT score (r = 0.81, p < 0.0001), conversely a negative correlation exists between the number of B-lines and diffusing capacity of the lung for carbon monoxide (DLCO) (r = -0.63, p < 0.0001). The number of B-lines increases along with the progression of the capillaroscopic damage. A statistically significant difference in the number of B-lines was found between patients with and without digital ulcers [42 (3-84) vs 16 (4-55)]. We found that the number of B-lines increased with the progression of both HRCT score and digital vascular damage. LUS may therefore, be a useful tool to determine the best timing for HRCT execution, thus, preventing for many patients a continuous and useless exposure to ionizing radiation.

  13. Correlation of serum hepcidin levels with disease progression in hepatitis B virus-related disease assessed by nanopore film based assay

    PubMed Central

    Wang, Jing; Dong, Ailian; Liu, Gang; Anderson, Gregory J.; Hu, Tony Y.; Shi, Jian; Hu, Yulin; Nie, Guangjun

    2016-01-01

    Chronic hepatitis B virus (HBV) infection often develop into cirrhosis, and both are major risk factors of hepatocellular carcinoma. However, effective approaches for the monitoring of HBV-related disease progress are still in need. Increased iron storage has an important role in HBV-related diseases. Hepcidin is a key regulator of iron homeostasis whose expression changes are often indicative of abnormal iron metabolism. There are few reports of hepcidin levels in patients with HBV infections, and the available results are inconsistent. In this study, using a recently validated nanopore silica film based method, we measured serum hepcidin levels in 46 HBV-related patients and 20 healthy controls. Patients were divided into three groups: chronic hepatitis B without cirrhosis; HBV-related cirrhosis; and HBV-related cirrhosis with hepatocellular carcinoma. Compared to healthy controls, the mean serum hepcidin level was significantly higher in CHB patients without cirrhosis, and in those with hepatocellular carcinoma, but not in those with cirrhosis. Iron-loading, viral infection and liver dysfunction are determined to be the major regulators of hepcidin in these patients. These observations suggest correlations between serum hepcidin and progression of chronic HBV infection, and may shed a new light on the development of biomarkers for HBV-related disease surveillance. PMID:27694815

  14. Multimodal Image Analysis in Alzheimer’s Disease via Statistical Modelling of Non-local Intensity Correlations

    NASA Astrophysics Data System (ADS)

    Lorenzi, Marco; Simpson, Ivor J.; Mendelson, Alex F.; Vos, Sjoerd B.; Cardoso, M. Jorge; Modat, Marc; Schott, Jonathan M.; Ourselin, Sebastien

    2016-04-01

    The joint analysis of brain atrophy measured with magnetic resonance imaging (MRI) and hypometabolism measured with positron emission tomography with fluorodeoxyglucose (FDG-PET) is of primary importance in developing models of pathological changes in Alzheimer’s disease (AD). Most of the current multimodal analyses in AD assume a local (spatially overlapping) relationship between MR and FDG-PET intensities. However, it is well known that atrophy and hypometabolism are prominent in different anatomical areas. The aim of this work is to describe the relationship between atrophy and hypometabolism by means of a data-driven statistical model of non-overlapping intensity correlations. For this purpose, FDG-PET and MRI signals are jointly analyzed through a computationally tractable formulation of partial least squares regression (PLSR). The PLSR model is estimated and validated on a large clinical cohort of 1049 individuals from the ADNI dataset. Results show that the proposed non-local analysis outperforms classical local approaches in terms of predictive accuracy while providing a plausible description of disease dynamics: early AD is characterised by non-overlapping temporal atrophy and temporo-parietal hypometabolism, while the later disease stages show overlapping brain atrophy and hypometabolism spread in temporal, parietal and cortical areas.

  15. COPD is associated with production of autoantibodies to a broad spectrum of self-antigens, correlative with disease phenotype

    PubMed Central

    Packard, Thomas A.; Li, Quan Z.; Cosgrove, Gregory P.; Bowler, Russell P.

    2014-01-01

    The role of autoimmune pathology in development and progression of chronic obstructive pulmonary disease (COPD) is becoming increasingly appreciated. In this study, we identified serum autoantibody reactivities associated with chronic bronchitis or emphysema, as well as systemic autoimmunity and associated lung disease. Using autoantigen array analysis, we demonstrated that COPD patients produce autoantibodies reactive to a broad spectrum of self-antigens. Further, the level and reactivities of these antibodies, or autoantibody profile, correlated with disease phenotype. Patients with emphysema produced autoantibodies of higher titer and reactive to an increased number of array antigens. Strikingly, the autoantibody reactivities observed in emphysema were increased over those detected in rheumatoid arthritis patients, and included similar reactivities to those associated with lupus. These findings raise the possibility that autoantibody profiles may be used to determine COPD risk, as well as provide a diagnostic and prognostic tool. They shed light on the heterogeneity of autoantibody reactivities associated with COPD phenotype and could be of use in the personalization of medical treatment, including determining and monitoring therapeutic interventions. PMID:22941590

  16. Multimodal Image Analysis in Alzheimer’s Disease via Statistical Modelling of Non-local Intensity Correlations

    PubMed Central

    Lorenzi, Marco; Simpson, Ivor J.; Mendelson, Alex F.; Vos, Sjoerd B.; Cardoso, M. Jorge; Modat, Marc; Schott, Jonathan M.; Ourselin, Sebastien

    2016-01-01

    The joint analysis of brain atrophy measured with magnetic resonance imaging (MRI) and hypometabolism measured with positron emission tomography with fluorodeoxyglucose (FDG-PET) is of primary importance in developing models of pathological changes in Alzheimer’s disease (AD). Most of the current multimodal analyses in AD assume a local (spatially overlapping) relationship between MR and FDG-PET intensities. However, it is well known that atrophy and hypometabolism are prominent in different anatomical areas. The aim of this work is to describe the relationship between atrophy and hypometabolism by means of a data-driven statistical model of non-overlapping intensity correlations. For this purpose, FDG-PET and MRI signals are jointly analyzed through a computationally tractable formulation of partial least squares regression (PLSR). The PLSR model is estimated and validated on a large clinical cohort of 1049 individuals from the ADNI dataset. Results show that the proposed non-local analysis outperforms classical local approaches in terms of predictive accuracy while providing a plausible description of disease dynamics: early AD is characterised by non-overlapping temporal atrophy and temporo-parietal hypometabolism, while the later disease stages show overlapping brain atrophy and hypometabolism spread in temporal, parietal and cortical areas. PMID:27064442

  17. Prominent effects and neural correlates of visual crowding in a neurodegenerative disease population

    PubMed Central

    Shakespeare, Timothy J.; Cash, Dave; Henley, Susie M. D.; Nicholas, Jennifer M.; Ridgway, Gerard R.; Golden, Hannah L.; Warrington, Elizabeth K.; Carton, Amelia M.; Kaski, Diego; Schott, Jonathan M.; Warren, Jason D.; Crutch, Sebastian J.

    2014-01-01

    Crowding is a breakdown in the ability to identify objects in clutter, and is a major constraint on object recognition. Crowding particularly impairs object perception in peripheral, amblyopic and possibly developing vision. Here we argue that crowding is also a critical factor limiting object perception in central vision of individuals with neurodegeneration of the occipital cortices. In the current study, individuals with posterior cortical atrophy (n = 26), typical Alzheimer’s disease (n = 17) and healthy control subjects (n = 14) completed centrally-presented tests of letter identification under six different flanking conditions (unflanked, and with letter, shape, number, same polarity and reverse polarity flankers) with two different target-flanker spacings (condensed, spaced). Patients with posterior cortical atrophy were significantly less accurate and slower to identify targets in the condensed than spaced condition even when the target letters were surrounded by flankers of a different category. Importantly, this spacing effect was observed for same, but not reverse, polarity flankers. The difference in accuracy between spaced and condensed stimuli was significantly associated with lower grey matter volume in the right collateral sulcus, in a region lying between the fusiform and lingual gyri. Detailed error analysis also revealed that similarity between the error response and the averaged target and flanker stimuli (but not individual target or flanker stimuli) was a significant predictor of error rate, more consistent with averaging than substitution accounts of crowding. Our findings suggest that crowding in posterior cortical atrophy can be regarded as a pre-attentive process that uses averaging to regularize the pathologically noisy representation of letter feature position in central vision. These results also help to clarify the cortical localization of feature integration components of crowding. More broadly, we suggest that posterior cortical

  18. Correlation between plasma lipoprotein-associated phospholipase A2 and peripheral arterial disease.

    PubMed

    Li, Shuai-Bing; Yang, Fan; Jing, Li; Ma, Juan; Jia, Ya-Dan; Dong, Shao-Ying; Zheng, Wei-Feng; Zhao, Luo-Sha

    2013-05-01

    Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a recently identified and potentially useful plasma biomarker for cardiovascular diseases. However, its role in peripheral arterial disease (PAD) remains unclear. The objective of this study was to assess the independent association of Lp-PLA2 and other inflammatory markers with the reduced ankle-brachial blood pressure index (ABI), a marker of PAD. We performed a cross-sectional study in 982 individuals aged ≥40 years who were recruited from the First Affiliated Hospital of Zhengzhou University. PAD was defined as an ABI <0.9 in at least one leg. The individuals were further divided into two groups, 145 with PAD and 837 without PAD. Following adjustment for traditional cardiovascular risk factors, the odds ratios of PAD when comparing the highest to the lowest quartiles were 3.24 (95% CI, 1.68-3.94) for Lp-PLA2, 2.14 (95% CI, 1.07-3.11) for homocysteine, 1.93 (95% CI, 1.02-4.01) for fibrinogen, 2.26 (95% CI, 1.32-5.74) for apolipoprotein B and 1.3 (95% CI, 0.75-2.49) for high-sensitivity C-reactive protein (hsCRP). When Lp-PLA2 and inflammatory markers were simultaneously included in the full model, the corresponding odds ratios were 1.81 (95% CI, 1.14-3.68) for Lp-PLA2, 1.15 (95% CI, 0.49-2.69) for homocysteine, 1.21 (95% CI, 0.88-5.57) for fibrinogen, 0.98 (95% CI, 0.51-3.85) for apolipoprotein B and 1.23 (95% CI, 1.12-3.51) for hsCRP. Lp-PLA2 levels were significantly and independently associated with PAD following adjustment for other inflammatory markers. These findings reflect the potential role of circulating Lp-PLA2 as a marker of atherosclerosis.

  19. Prominent effects and neural correlates of visual crowding in a neurodegenerative disease population.

    PubMed

    Yong, Keir X X; Shakespeare, Timothy J; Cash, Dave; Henley, Susie M D; Nicholas, Jennifer M; Ridgway, Gerard R; Golden, Hannah L; Warrington, Elizabeth K; Carton, Amelia M; Kaski, Diego; Schott, Jonathan M; Warren, Jason D; Crutch, Sebastian J

    2014-12-01

    Crowding is a breakdown in the ability to identify objects in clutter, and is a major constraint on object recognition. Crowding particularly impairs object perception in peripheral, amblyopic and possibly developing vision. Here we argue that crowding is also a critical factor limiting object perception in central vision of individuals with neurodegeneration of the occipital cortices. In the current study, individuals with posterior cortical atrophy (n=26), typical Alzheimer's disease (n=17) and healthy control subjects (n=14) completed centrally-presented tests of letter identification under six different flanking conditions (unflanked, and with letter, shape, number, same polarity and reverse polarity flankers) with two different target-flanker spacings (condensed, spaced). Patients with posterior cortical atrophy were significantly less accurate and slower to identify targets in the condensed than spaced condition even when the target letters were surrounded by flankers of a different category. Importantly, this spacing effect was observed for same, but not reverse, polarity flankers. The difference in accuracy between spaced and condensed stimuli was significantly associated with lower grey matter volume in the right collateral sulcus, in a region lying between the fusiform and lingual gyri. Detailed error analysis also revealed that similarity between the error response and the averaged target and flanker stimuli (but not individual target or flanker stimuli) was a significant predictor of error rate, more consistent with averaging than substitution accounts of crowding. Our findings suggest that crowding in posterior cortical atrophy can be regarded as a pre-attentive process that uses averaging to regularize the pathologically noisy representation of letter feature position in central vision. These results also help to clarify the cortical localization of feature integration components of crowding. More broadly, we suggest that posterior cortical atrophy

  20. Behavioral and Electrophysiological Correlates of Memory Binding Deficits in Patients at Different Risk Levels for Alzheimer's Disease.

    PubMed

    Pietto, Marcos; Parra, Mario A; Trujillo, Natalia; Flores, Facundo; García, Adolfo M; Bustin, Julian; Richly, Pablo; Manes, Facundo; Lopera, Francisco; Ibáñez, Agustín; Baez, Sandra

    2016-06-30

    Deficits in visual short-term memory (VSTM) binding have been proposed as an early and specific marker for Alzheimer's disease (AD). However, no studies have explored the neural correlates of this domain in clinical categories involving prodromal stages with different risk levels of conversion to AD. We assessed underlying electrophysiological modulations in patients with mild cognitive impairment (MCI), patients in the MCI stages of familial AD carrying the mutation E280A of the presenilin-1 gene (MCI-FAD), and healthy controls. Moreover, we compared the behavioral performance and neural correlates of both patient groups. Participants completed a change-detection VSTM task assessing recognition of changes between shapes or shape-color bindings, presented in two consecutive arrays (i.e., study and test) while event related potentials (ERPs) were recorded. Changes always occurred in the test array and consisted of new features replacing studied features (shape-only) or features swapping across items (shape-color binding). Both MCI and MCI-FAD patients performed worse than controls in the shape-color binding condition. Early electrophysiological activity (100-250 ms) was significantly reduced in both clinical groups, particularly over fronto-central and parieto-occipital regions. However, shape-color binding performance and their reduced neural correlates were similar between MCI and MCI-FAD. Our results support the validity of the VSTM binding test and their neural correlates in the early detection of AD and highlight the importance of studies comparing samples at different risk for AD conversion. The combined analysis of behavioral and ERP data gleaned with the VSTM binding task can offer a valuable memory biomarker for AD.

  1. Depressive symptoms in prodromal Huntington's Disease correlate with Stroop-interference related functional connectivity in the ventromedial prefrontal cortex

    PubMed Central

    Unschuld, Paul G.; Joel, Suresh E.; Pekar, James J.; Reading, Sarah A.; Oishi, Kenichi; McEntee, Julie; Shanahan, Megan; Bakker, Arnold; Margolis, Russell L.; Bassett, Susan S.; Rosenblatt, Adam; Mori, Susumu; van Zijl, Peter C.; Ross, Christopher A.; Redgrave, Graham W.

    2012-01-01

    Huntington's Disease (HD) is a neurodegenerative disorder caused by a cytosine-adenine-guanine (CAG) triplet repeat-expansion in the Huntingtin (HTT) gene. Diagnosis of HD is classically defined by the presence of motor symptoms; however cognitive and depressive symptoms frequently precede motor manifestation, and may occur early in the prodromal phase. There are sparse data so far on functional brain correlates of depressive symptoms in prodromal-HD. A Stroop color-naming test was administered to 32 subjects in the prodromal phase of HD and 52 expansion-negative controls while performing functional magnetic resonance imaging at 3 Tesla. Networks of functional connectivity were identified using group independent component analysis, followed by an analysis of functional network interactions. A contrast of temporal regression-based beta-weights was calculated as a reflection of Stroop-interference related activity and correlated with Center for Epidemiologic Studies Depression (CES-D) scores. For secondary analysis, patients were stratified in two subgroups by median split of CAG repeat-length. Stroop-performance was independent of HTT mutation-carrier-status and CES-D score. Stroop-interference related activity of the ventromedial prefrontal cortex-node of the default-mode network, calculated by temporal-regression beta-weights, was more highly correlated with depressive symptoms in subjects in the prodromal phase of HD than in controls, differing significantly. The strength of this correlation and its difference from controls increased when a subgroup of patients with longer CAG repeat lengths was analyzed. These findings suggest that depressive symptoms in prodromal-HD subjects may reflect altered functional brain network activity in the context of early HD related brain alterations. PMID:22974690

  2. Biomarkers of the osteoprotegerin pathway: clinical correlates, subclinical disease, incident CVD and mortality

    PubMed Central

    Lieb, Wolfgang; Gona, Philimon; Larson, Martin G.; Massaro, Joseph M; Lipinska, Izabella; Keaney, John F.; Rong, Jian; Corey, Diane; Hoffmann, Udo; Fox, Caroline S; Vasan, Ramachandran S.; Benjamin, Emelia J.; O’Donnell, Christopher J; Kathiresan, Sekar

    2011-01-01

    Objective Experimental evidence identified the osteoprotegerin [OPG]/receptor activator of nuclear factor–kappa-B [RANK]/RANK ligand [RANKL] pathway as a candidate system modulating vascular remodeling and cardiovascular disease (CVD). Methods and Results Serum concentrations of OPG and RANKL were measured in 3250 Framingham Study participants (54% women, 61±9 years). During a median follow-up of 4.6 years, 143 (of 3084 free of CVD at baseline) participants developed a first CVD event and 235 died. In multivariable models OPG was associated with increased hazards for incident CVD and mortality (HR: 1.27; 95% CI, 1.04 to 1.54 and HR: 1.25; 95% CI, 1.07 to 1.47 per one-SD increment in log-OPG, respectively). Log-OPG was positively related to multiple CVD risk factors including age, smoking, diabetes, systolic blood pressure and prevalent CVD. In a subsample (n=1264), the prevalence of coronary artery calcification, measured by computed tomography, increased non-significantly with OPG-quartiles. RANKL concentrations displayed inverse associations with multiple CVD risk factors including smoking, diabetes and antihypertensive treatment, and were not related to coronary artery calcification or incident CVD or mortality. Conclusions Our prospective data reinforce OPG as marker for CVD risk factor burden and predictor for CVD and mortality in the community. PMID:20448212

  3. Apathy in Parkinson’s Disease: Diagnosis, Neuropsychological Correlates, Pathophysiology and Treatment

    PubMed Central

    Santangelo, Gabriella; Trojano, Luigi; Barone, Paolo; Errico, Domenico; Grossi, Dario; Vitale, Carmine

    2013-01-01

    Apathy has been defined as lack of motivation. It has been traditionally considered as a symptom of psychiatric disorders, such as major depression and schizophrenia, but more recently it has been recognized as a specific neuropsychiatric syndrome associated with neurodegenerative such as Parkinson’s disease (PD). As a consequence the reported prevalence of apathy in PD ranges from 13.9% to 70%; the mean prevalence is 35%. Prevalence of “pure apathy” (i.e., of apathy without comorbid depression and dementia) seems to be substantially lower, from 3 to 47.9%. High levels of apathy in PD are associated with decreased daily function, specific cognitive deficits and increased stress for families. Although neuroimaging studies do not provide a unique anatomic pattern, several data suggest that the ventromedial prefrontal cortex and the basal ganglia connected through frontal-subcortical circuits, are particularly involved in the genesis of apathy. At present, there are no approved medications for the treatment of apathy in and no proof of efficacy exists for any drug in current use. Further studies and innovative pharmacologic approaches are thus needed to ameliorate our understanding and treatment of apathy in PD. PMID:23242365

  4. Deficiency of ganglioside GM1 correlates with Parkinson's disease in mice and humans.

    PubMed

    Wu, Gusheng; Lu, Zi-Hua; Kulkarni, Neil; Ledeen, Robert W

    2012-10-01

    Several studies have successfully employed GM1 ganglioside to treat animal models of Parkinson's disease (PD), suggesting involvement of this ganglioside in PD etiology. We recently demonstrated that genetically engineered mice (B4galnt1(-/-) ) devoid of GM1 acquire characteristic symptoms of this disorder, including motor impairment, depletion of striatal dopamine, selective loss of tyrosine hydroxylase-expressing neurons, and aggregation of α-synuclein. The present study demonstrates similar symptoms in heterozygous mice (HTs) that express only partial GM1 deficiency. Symptoms were alleviated by administration of L-dopa or LIGA-20, a membrane-permeable analog of GM1 that penetrates the blood-brain barrier and accesses intracellular compartments. Immunohistochemical analysis of paraffin sections from PD patients revealed significant GM1 deficiency in nigral dopaminergic neurons compared with age-matched controls. This was comparable to the GM1 deficiency of HT mice and suggests that GM1 deficiency may be a contributing factor to idiopathic PD. We propose that HT mice with partial GM1 deficiency constitute an especially useful model for PD, reflecting the actual pathophysiology of this disorder. The results point to membrane-permeable analogs of GM1 as holding promise as a form of GM1 replacement therapy.

  5. A systematic review of the psychological correlates of adjustment outcomes in adults with inflammatory bowel disease.

    PubMed

    Jordan, Cheryl; Sin, Jacqueline; Fear, Nicola T; Chalder, Trudie

    2016-07-01

    Inflammatory bowel disease (IBD) is a chronic long term condition which poses significant psychosocial adjustment challenges. The purpose of this review was to systematically identify psychological factors related to adjustment in adults with IBD with the aim of suggesting evidence based targets that may be modifiable though psychological intervention. Twenty five studies met inclusion criteria and were included in the systematic review and a narrative synthesis was conducted. A wide range of psychological variables were addressed covering six broad categories; personality traits, interpersonal traits, stress and coping, emotions and emotional control, IBD related cognitions and non IBD related cognitions. The most consistent relationship was found between certain emotion focused coping strategies and worse adjustment outcomes in IBD. Some evidence also hi-lighted a relationship between personality traits (such as neuroticism,) perceived stress, emotions and emotional control (such as alexithymia) and IBD related cognitions (such as illness perceptions) and negative adjustment outcomes. The results of this review suggest that interventions to improve adjustment in IBD may benefit from a focus on coping strategies, perceived stress and IBD related cognitions.

  6. Gene expression correlates of neurofibrillary tangles in Alzheimer’s disease

    PubMed Central

    Dunckley, Travis; Beach, Thomas G.; Ramsey, Keri E.; Grover, Andrew; Mastroeni, Diego; Walker, Douglas G.; LaFleur, Bonnie J.; Coon, Keith D.; Brown, Kevin M.; Caselli, Richard; Kukull, Walter; Higdon, Roger; McKeel, Daniel; Morris, John C.; Hulette, Christine; Schmechel, Donald; Reiman, Eric M.; Rogers, Joseph; Stephan, Dietrich A.

    2008-01-01

    Neurofibrillary tangles (NFT) constitute one of the cardinal histopathological features of Alzheimer’s disease (AD). To explore in vivo molecular processes involved in the development of NFTs, we compared gene expression profiles of NFT-bearing entorhinal cortex neurons from 19 AD patients, adjacent non-NFT-bearing entorhinal cortex neurons from the same patients, and non-NFT-bearing entorhinal cortex neurons from 14 non-demented, histopathologically normal controls (ND). Of the differentially expressed genes, 225 showed progressively increased expression (AD NFT neurons > AD non-NFT neurons > ND non-NFT neurons) or progressively decreased expression (AD NFT neurons < AD non-NFT neurons < ND non-NFT neurons), raising the possibility that they may be related to the early stages of NFT formation. Immunohistochemical studies confirmed that many of the implicated proteins are dysregulated and preferentially localized to NFTs, including apolipoprotein J, interleukin-1 receptor-associated kinase 1, tissue inhibitor of metalloproteinase 3, and casein kinase 2, beta. Functional validation studies are underway to determine which candidate genes may be causally related to NFT neuropathology, thus providing therapeutic targets for the treatment of AD. PMID:16242812

  7. Computed tomography findings of hepatic veno-occlusive disease caused by Sedum aizoon with histopathological correlation

    PubMed Central

    Shao, H.; Chen, H. Z.; Zhu, J. S.; Ruan, B.; Zhang, Z. Q.; Lin, X.; Gan, M. F.

    2015-01-01

    This study investigated the value of computed tomography (CT) in the diagnosis and treatment of hepatic veno-occlusive disease (HVOD) caused by Sedum aizoon (SA). The clinical manifestations, treatment results, imaging findings, and histological findings of the liver were analyzed in 39 patients with HVOD caused by SA. Hepatomegaly, liver dysfunction, abdominal effusion, and geographic density changes on liver CT scans were found in all 39 patients. The pathological findings of histological liver examination included swelling and point-like necrosis of liver cells, significant expansion and congestion of the sinuses, endothelial swelling, and wall thickening with incomplete lumen occlusion of small liver vessels. CT geographic density changes were confirmed by histological examination of the liver in 18 patients. Sixteen patients with small amounts of ascites that started within 4 weeks of treatment recovered completely or significantly improved after symptomatic and supportive treatment. However, only 43.75% of the patients with larger amounts of ascites improved following symptomatic and supportive treatment. In conclusion, liver CT examination is a valuable, safe, and noninvasive tool for the diagnosis of HVOD caused by SA. In selected cases, liver CT examination may replace liver biopsy and histological analysis. PMID:26517336

  8. CLINICAL CORRELATES OF PERIODIC LIMB MOVEMENTS IN SLEEP IN PARKINSON’S DISEASE

    PubMed Central

    Covassin, Naima; Neikrug, Ariel B.; Liu, Lianqi; Corey-Bloom, Jody; Loredo, Jose S.; Palmer, Barton W.; Maglione, Jeanne; Ancoli-Israel, Sonia

    2012-01-01

    Objective The aim of the current study was to investigate the frequency of periodic limb movements in sleep (PLMS) in Parkinson’s disease (PD) and their impact on nocturnal sleep and daytime functioning. Methods Forty-five PD patients (mean age 68.5±8.7 years; 32 males) underwent one night of polysomnography (PSG). Clinical assessment and questionnaires evaluating sleep disturbance and quality of life (QoL) were completed. Patients were divided into two groups based on their PLMS index (PLMSI): PLMSI ≥15 (PLMS+) and PLMSI <15 (PLMS−). Results There were 26 (57.8%) PD patients in the PLMS+ group and 19 (42.2%) patients in the PLMS− group. Subjective assessment revealed an association between PLMS+ status and greater PD symptom severity, more subjective sleep disturbance, and decreased QoL. All patients showed poor sleep, and no significant group differences were detected on PSG measures. Conclusion We observed that PLMS occurred frequently in PD and increased with more severe PD. Although PLMS did not affect objective sleep, it was associated with increased sleep complaints and reduced QoL. Overall, our findings support the association between PLMS and PD as well as the clinical relevance of sleep disturbances in PD. PMID:22277375

  9. Positron emission tomographic scan investigations of Huntington's disease: cerebral metabolic correlates of cognitive function

    SciTech Connect

    Berent, S.; Giordani, B.; Lehtinen, S.; Markel, D.; Penney, J.B.; Buchtel, H.A.; Starosta-Rubinstein, S.; Hichwa, R.; Young, A.B.

    1988-06-01

    Fifteen drug-free patients with early to mid-stage Huntington's disease (HD) were evaluated with positron emission tomographic (PET) scans of /sup 18/F-2-fluoro-2-deoxy-D-glucose uptake and quantitative measures of neurological function, learning, memory, and general intelligence. In comparison with a group of normal volunteers, the HD patients showed lower metabolism in both caudate (p less than 0.001) and putamen (p less than 0.001) on PET scans. A significant and positive relationship was found between neuropsychological measures of verbal learning and memory and caudate metabolism in the patient group but not in the normal group. Visual-spatial learning did not reflect a similar pattern, but performance intelligence quotient was positively related to both caudate and putamen metabolism in the HD group. Vocabulary level was unrelated to either brain structure. Discussion focuses on these and other observed brain-behavior relationships and on the implications of these findings for general behaviors such as those involved in coping and adaptation.

  10. Festination Correlates with SNCA Polymorphism in Chinese Patients with Parkinson's Disease

    PubMed Central

    Yang, Xinglong; Huang, Hongyan

    2017-01-01

    The genetic basis of festination, a common motor symptom in Parkinson's disease (PD), remains unclear. Since polymorphism in the alpha-synuclein (SNCA) gene is associated with PD phenotype, we examined whether such polymorphism is also associated with festination. SNCA polymorphisms rs11931074 and rs894278 were genotyped in a consecutive series of 258 patients with PD, of whom 122 (47.3%) suffered festination. Univariate analysis revealed significant differences in genotype and minor allele frequencies at rs11931074 or rs894278 between patients with festination and those without it (all p < 0.05). Based on logistic regression, a GG or GT genotype at rs11931074 was associated with higher risk of festination among patients with PD (OR 2.077, 95% CI 1.111–3.883, p = 0.022), as was the TT genotype at rs894278 (OR 2.271, 95% CI 1.246–4.139, p = 0.007). Therefore, we conclude that festination is associated with polymorphism at rs11931074 or rs894278 among patients with PD. PMID:28357149

  11. Clinical-physiologic correlates of Alzheimer's disease and frontal lobe dementia

    SciTech Connect

    Jagust, W.J.; Reed, B.R.; Seab, J.P.; Kramer, J.H.; Budinger, T.F. )

    1989-01-01

    Thirty patients with degenerative dementia underwent clinical evaluation, neuropsychological testing, and single photon emission computed tomography (SPECT) with the blood flow tracer ({sup 123}I)-N-isopropyl-p-iodoamphetamine. Five of these patients were clinically and psychologically different from the others, demonstrating predominant behavioral disturbances with relative preservation of memory function. These five patients, who were felt to have a frontal lobe dementia (FLD), showed SPECT perfusion patterns which differed from the remaining 25 patients, who were diagnosed as having Alzheimer's disease (AD), and from 16 healthy control subjects. The FLD patients showed diminished perfusion in orbitofrontal, dorsolateral frontal, and temporal cortex relative to controls, while the AD patients showed lower perfusion in temporal and parietal cortex than controls. The FLD patients also showed hypoperfusion in both frontal cortical regions relative to AD patients. The pattern of performance on neuropsychological testing paralleled these differences in regional perfusion. These results suggest that clinical evaluation and physiological imaging may enable the differentiation of groups of degenerative dementia patients during life.

  12. Trends, correlates, and disease patterns of antidepressant use among children and adolescents in Taiwan.

    PubMed

    Chien, I-Chia; Hsu, Yuan-Chang; Tan, Happy Kuy-Lok; Lin, Ching-Heng; Cheng, Shu-Wen; Chou, Yiing-Jenq; Chou, Pesus

    2013-06-01

    The authors used a population-based database to investigate antidepressant use among children and adolescents in Taiwan. The National Health Research Institutes provided a database of 1 000 000 random subjects for study. The authors adopted this sample of subjects who were younger than 18 years during 1997 to 2005. Subjects with at least 1 antidepressant prescription were identified. Trends, prevalence, associated factors, and disease patterns of antidepressant use were detected. The 1-year prevalence of pediatric antidepressant use increased from 0.27% in 1997 to 0.47% in 2005. The 1-year prevalence of tricyclic antidepressant, selective serotonin reuptake inhibitor, and other antidepressant use among pediatric population was 0.23%, 0.20%, and 0.08%, respectively, in 2005. The prevalence of pediatric antidepressant use increased from 1997 to 2005. Among pediatric subjects with antidepressant use, selective serotonin reuptake inhibitors, and other antidepressants were used the most for psychiatric disorders, whereas tricyclic antidepressant was used the most for nonpsychiatric disorders.

  13. Detecting sarcasm from paralinguistic cues: anatomic and cognitive correlates in neurodegenerative disease.

    PubMed

    Rankin, Katherine P; Salazar, Andrea; Gorno-Tempini, Maria Luisa; Sollberger, Marc; Wilson, Stephen M; Pavlic, Danijela; Stanley, Christine M; Glenn, Shenly; Weiner, Michael W; Miller, Bruce L

    2009-10-01

    While sarcasm can be conveyed solely through contextual cues such as counterfactual or echoic statements, face-to-face sarcastic speech may be characterized by specific paralinguistic features that alert the listener to interpret the utterance as ironic or critical, even in the absence of contextual information. We investigated the neuroanatomy underlying failure to understand sarcasm from dynamic vocal and facial paralinguistic cues. Ninety subjects (20 frontotemporal dementia, 11 semantic dementia [SemD], 4 progressive non-fluent aphasia, 27 Alzheimer's disease, 6 corticobasal degeneration, 9 progressive supranuclear palsy, 13 healthy older controls) were tested using the Social Inference - Minimal subtest of The Awareness of Social Inference Test (TASIT). Subjects watched brief videos depicting sincere or sarcastic communication and answered yes-no questions about the speaker's intended meaning. All groups interpreted Sincere (SIN) items normally, and only the SemD group was impaired on the Simple Sarcasm (SSR) condition. Patients failing the SSR performed more poorly on dynamic emotion recognition tasks and had more neuropsychiatric disturbances, but had better verbal and visuospatial working memory than patients who comprehended sarcasm. Voxel-based morphometry analysis of SSR scores in SPM5 demonstrated that poorer sarcasm comprehension was predicted by smaller volume in bilateral posterior parahippocampi (PHc), temporal poles, and R medial frontal pole (pFWE<0.05). This study provides lesion data suggesting that the PHc may be involved in recognizing a paralinguistic speech profile as abnormal, leading to interpretive processing by the temporal poles and right medial frontal pole that identifies the social context as sarcastic, and recognizes the speaker's paradoxical intentions.

  14. Vertically acquired hepatitis C virus infection: Correlates of transmission and disease progression

    PubMed Central

    Tovo, Pier-Angelo; Calitri, Carmelina; Scolfaro, Carlo; Gabiano, Clara; Garazzino, Silvia

    2016-01-01

    The worldwide prevalence of hepatitis C virus (HCV) infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, mother-to-child transmission (MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance (SVC) that usually occurs within 6 years of life. IL-28B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare. PMID:26819507

  15. Correlation of serum alanine aminotransferase and aspartate aminotransferase with coronary heart disease

    PubMed Central

    Shen, Jianying; Zhang, Jingying; Wen, Jing; Ming, Qiang; Zhang, Ji; Xu, Yawei

    2015-01-01

    Objective: This study aimed to explore the relationship between different risk factors (especially serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST]) and coronary heart disease (CHD). Methods: A total of 610 inpatients were recruited. Initial coronary angiography (CAG) was performed to evaluate the severity of coronary lesions. On the basis of findings from CAG, patients were divided into control group (n=260) and CHD group (n=350). Logistic regression analysis was employed for the evaluation of clinical characteristics and biochemical parameters, aiming to explore the relationship between risk factors (including AST and ALT) and CHD. Results: Results showed type 2 diabetes, hypertension, dyslipidemia, smoking and family history of CHD were clinical risk factors of CHD. Laboratory examinations showed the serum levels of triglycerides, low-density lipoprotein, AST and ALT in CHD group were significantly higher than those in control group (P<0.05). Of these parameters, the AST was 50.98±8.12 U/L in CHD group and 20.14±3.94 U/L in control group (P<0.01); the ALT was 42.31±8.34 U/L in CHD group and 18.25±6.38 U/L in control group (P<0.01). Conclusion: The serum levels of AST and ALT in CHD patients are higher than those in controls. High serum AST and ALT are biochemical markers which can be used to predict the severity of CHD and are also independent risk factors of CHD. PMID:26064360

  16. Neurofunctional correlates of attention rehabilitation in Parkinson's disease: an explorative study.

    PubMed

    Cerasa, Antonio; Gioia, Maria Cecilia; Salsone, Maria; Donzuso, Giulia; Chiriaco, Carmelina; Realmuto, Sabrina; Nicoletti, Alessandra; Bellavia, Gabriele; Banco, Aurelia; D'amelio, Marco; Zappia, Mario; Quattrone, Aldo

    2014-08-01

    The effectiveness of cognitive rehabilitation (CR) in Parkinson's disease (PD) is in its relative infancy, and nowadays there is insufficient information to support evidence-based clinical protocols. This study is aimed at testing a validated therapeutic strategy characterized by intensive computer-based attention-training program tailored to attention deficits. We further investigated the presence of synaptic plasticity by means of functional magnetic resonance imaging (fMRI). Using a randomized controlled study, we enrolled eight PD patients who underwent a CR program (Experimental group) and seven clinically/demographically-matched PD patients who underwent a placebo intervention (Control group). Brain activity was assessed using an 8-min resting state (RS) fMRI acquisition. Independent component analysis and statistical parametric mapping were used to assess the effect of CR on brain function. Significant effects were detected both at a phenotypic and at an intermediate phenotypic level. After CR, the Experimental group, in comparison with the Control group, showed a specific enhanced performance in cognitive performance as assessed by the SDMT and digit span forward. RS fMRI analysis for all networks revealed two significant groups (Experimental vs Control) × time (T0 vs T1) interaction effects on the analysis of the attention (superior parietal cortex) and central executive neural networks (dorsolateral prefrontal cortex). We demonstrated that intensive CR tailored for the impaired abilities impacts neural plasticity and improves some aspects of cognitive deficits of PD patients. The reported neurophysiological and behavioural effects corroborate the benefits of our therapeutic approach, which might have a reliable application in clinical management of cognitive deficits.

  17. Wilson disease: novel mutations in the ATP7B gene and clinical correlation in Brazilian patients.

    PubMed

    Deguti, Marta M; Genschel, Janine; Cancado, Eduardo L R; Barbosa, Egberto R; Bochow, Bettina; Mucenic, Marcos; Porta, Gilda; Lochs, Herbert; Carrilho, Flair J; Schmidt, Hartmut H-J

    2004-04-01

    Wilson disease (WD) is a rare inherited autosomal recessive disorder caused by a defect in a metal transporting P-type ATPase, resulting in copper overload in various tissues and cells. The aim was to assess both the phenotype in Brazilian WD patients and the corresponding ATP7B genotype. Sixty subjects belonging to 46 pedigrees diagnosed as WD were included in this study. Direct sequencing of all 21 exons within ATP7B and their flanking introns was performed. Demographic, clinical, laboratory and histopathological data at the time of diagnosis were obtained. We identified twenty-five mutations, twelve of them reported for the first time. The c.3402delC mutation had the highest allelic frequency (30.8%), followed by the c.2123T>C (p.L708P) (16.7%). Exons 8 and 15 were the site of 62.5% of the mutations. The common European mutation c.3207C>A (p.H1069Q) was not present at all. Phenotype varied greatly among individuals with the same ATP7B genotype. Our data confirm the heterogeneity of ATP7B genotype in Brazilian WD patients. The mutational spectrum is compatible with the Brazilian history of Mediterranean immigration; however, new mutations, and different frequencies and phenotype associated with the previously known mutations characterize this population. Exons 8 and 15 should be preferentially screened in WD cases from Brazil. Phenotype variation among subjects with the same ATP7B genotype suggests that modifying factors play an additional role in the pathogenesis of WD.

  18. Correlation between single nucleotide polymorphism of FCRL-3 gene and Graves’ disease in Han population of northern Anhui province, China

    PubMed Central

    Jin, Guo-Xi; Zhou, Yu-Ye; Yu, Lei; Bi, Ya-Xin

    2015-01-01

    Objective: The frequency distribution of A/G genotype at position-169 in promoter of FCRL3 gene (Fc receptor-like 3) was identified in Han population of northern Anhui Province. The correlation between single nucleotide polymorphism (SNP) at this site and genetic susceptibility of Graves disease (GD) was discussed. How the genotype at this position correlated to age, gender, severity of goiter, presence or absence of exophthalmos, levels of thyrotrophin receptor antibody (TRab), thyroid peroxidase antibody (TpoAb) and anti-thyroglobulin antibody (TgAb) and thyroid function was analyzed in details. Method: Peripheral venous blood was collected for DNA extraction. SNP at position-169 in the promoter of FCRL3 gene was determined by using PCR-RELP among 180 GD cases and 146 normal subjects. Thyroid function tests and antibody detection were performed. Results: The frequency of GG genotype of position-169 in promoter of FCRL3 gene was higher in GD group than in control group. The frequency was 28.9% and 13.8%, respectively, showing significant differences in intergroup comparison (χ2=6.618, P=0.046). The G allele frequency of GD group and control group was 49.4% and 40.4%, respectively, also showing significant differences between the groups (χ2=5.308, P=0.021). GD cases with AA, AG and GG genotypes at position-169 in FCRL3 promoter had significant differences in serum level of TRAb (χ2=7.319, P=0.026). However, no significant differences in gender, severity of goiter, TpoAb and TgAb level, presence or absence of exophthalmos and thyroid function (FT3, FT4, TSH) were found between the three genotypes (P>0.05). Conclusion: A/G SNP at position-169 in promoter of FCRL3 gene was correlated with susceptibility to GD among Han population in northern Anhui Province. G allele may contribute to the susceptibility to GD and correlate to positive TRAb result in thyroid diseases, but not to age of onset, gender, presence or absence of exophthalmos, thyroid function, TpoAb and Tg

  19. Nailfold capillaroscopic changes in patients with systemic lupus erythematosus: correlations with disease activity, skin manifestation and nephritis.

    PubMed

    Shenavandeh, S; Habibi, S

    2017-01-01

    Introduction The clinical expression of systemic lupus erythematosus (SLE) is the consequence of endothelial cell damage leading to serious multiple organ dysfunction. The aim of this study was to assess the association between nailfold capillaroscopic changes and disease activity, skin and renal involvement in patients with SLE. Methods Demographic variables, clinical manifestations and laboratory data of 108 patients with SLE were investigated. Nailfold capillaroscopy (NFC) was performed in all patients. Result Morphological changes in NFC were observed in 102 out of 108 (94.4%) SLE patients. Minor changes were found in 33 (30.6%) and major changes in 69 (63.9%) cases. The disease activity was significantly higher in the patients with major changes ( p < 0.002). A higher incidence of microhaemorrhages was seen in patients with active SLE disease ( p < 0.04). In SLE patients with active skin involvement, the disturbed distribution ( p < 0.004) was more frequent and subtle changes ( p < 0.009) were less frequently observed as compared with patients without active skin involvement. In the group of SLE patients with renal involvement, no correlation was found between the capillary abnormalities and the presence of renal involvement ( p > 0.05), except for the elongated capillary loops, which were seen more often in patients with renal involvement than in patients without it ( p < 0.03). Conclusion The results of the study showed that capillary changes (abnormal capillaroscopy) were very common in patients with SLE, although there were no specific patterns like the ones in scleroderma patients, and some changes may be associated with disease activity, especially in patients with active skin involvement.

  20. Kingella kingae Expresses Four Structurally Distinct Polysaccharide Capsules That Differ in Their Correlation with Invasive Disease

    PubMed Central

    Porsch, Eric A.; Seed, Patrick C.; Heiss, Christian; Naran, Radnaa; Amit, Uri; Yagupsky, Pablo; Azadi, Parastoo; St. Geme, Joseph W.

    2016-01-01

    Kingella kingae is an encapsulated gram-negative organism that is a common cause of osteoarticular infections in young children. In earlier work, we identified a glycosyltransferase gene called csaA that is necessary for synthesis of the [3)-β-GalpNAc-(1→5)-β-Kdop-(2→] polysaccharide capsule (type a) in K. kingae strain 269–492. In the current study, we analyzed a large collection of invasive and carrier isolates from Israel and found that csaA was present in only 47% of the isolates. Further examination of this collection using primers based on the sequence that flanks csaA revealed three additional gene clusters (designated the csb, csc, and csd loci), all encoding predicted glycosyltransferases. The csb locus contains the csbA, csbB, and csbC genes and is associated with a capsule that is a polymer of [6)-α-GlcpNAc-(1→5)-β-(8-OAc)Kdop-(2→] (type b). The csc locus contains the cscA, cscB, and cscC genes and is associated with a capsule that is a polymer of [3)-β-Ribf-(1→2)-β-Ribf-(1→2)-β-Ribf-(1→4)-β-Kdop-(2→] (type c). The csd locus contains the csdA, csdB, and csdC genes and is associated with a capsule that is a polymer of [P-(O→3)[β-Galp-(1→4)]-β-GlcpNAc-(1→3)-α-GlcpNAc-1-] (type d). Introduction of the csa, csb, csc, and csd loci into strain KK01Δcsa, a strain 269–492 derivative that lacks the native csaA gene, was sufficient to produce the type a capsule, type b capsule, type c capsule, and type d capsule, respectively, indicating that these loci are solely responsible for determining capsule type in K. kingae. Further analysis demonstrated that 96% of the invasive isolates express either the type a or type b capsule and that a disproportionate percentage of carrier isolates express the type c or type d capsule. These results establish that there are at least four structurally distinct K. kingae capsule types and suggest that capsule type plays an important role in promoting K. kingae invasive disease. PMID:27760194

  1. Positive correlation between variants of lipid metabolism-related genes and coronary heart disease

    PubMed Central

    ZHANG, LI-NA; LIU, PAN-PAN; ZHOU, JIANQING; HUANG, R. STEPHANIE; YUAN, FANG; FEI, LI-JUAN; HUANG, YI; XU, LIMIN; HAO, LING-MEI; QIU, XU-JUN; LE, YANPING; YANG, XI; XU, WEIFENG; HUANG, XIAOYAN; YE, MENG; LIAN, JIANGFANG; DUAN, SHIWEI

    2013-01-01

    Four gene variants related to lipid metabolism (including the rs562338 and rs503662 variants of the APOB gene, the rs7767084 variant of the LPA gene and the rs2246942 variant of the LIPA gene) have been shown to be associated with coronary heart disease (CHD). The aim of the present study was to assess their association with CHD in the Han Chinese population and to assess the contribution of these gene variants to CHD. Using the standardized coronary angiography method, we enrolled 290 CHD patients and 193 non-CHD patients as non-CHD controls from Lihuili Hospital (Ningbo, China). In addition, we recruited 330 unrelated healthy volunteers as healthy controls from the Xi Men Community (Ningbo, China). Our results demonstrated that the rs503662 and rs562338 variants of the APOB gene were extremely rare in the Han Chinese population (minor allele frequency <1%). Genotype rs2246942-GG of the LIPA gene was associated with an increased risk of CHD [CHD cases versus healthy controls: P=0.04; odds ratio (OR)=1.63; 95% confidence interval (CI)=1.02–2.60). Genotype rs7767084-CC of the LPA gene was identified as a protective factor against CHD in females (CHD cases versus non-CHD controls: P=0.04, OR=0.21; CHD cases versus healthy controls: P=0.02, OR=0.21). The results of our meta-analysis indicated that rs7767084 was not associated with a high risk of CHD (P=0.83; combined OR=0.93; 95% CI=0.47–1.85). In the present study, two single nucleotide polymorphisms (SNPs) of genes involved in lipid metabolism (rs2246942 and rs7767084) were identified to be significantly associated with CHD in the Han Chinese population. Specifically, rs2246942-GG of the LIPA gene was a risk factor for CHD, while rs7767084-CC of the LPA gene was a protective factor against CHD in females. However, our meta-analysis indicated that rs7767084 is not associated with a higher risk of CHD. PMID:23653095

  2. DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2

    PubMed Central

    Poirier, John T.; Gardner, Eric E.; Connis, Nick; Moreira, Andre L.; de Stanchina, Elisa; Hann, Christine L.; Rudin, Charles M.

    2015-01-01

    Small cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastasis, rapid development of resistance to chemotherapy, and genetic instability. This study profiles DNA methylation in SCLC, patient-derived xenografts (PDXs) and cell lines at single nucleotide resolution. DNA methylation patterns of primary samples are distinct from those of cell lines, while PDXs maintain a pattern closely consistent with primary samples. Clustering of DNA methylation and gene expression of primary SCLC revealed distinct disease subtypes among histologically indistinguishable primary patient samples with similar genetic alterations. SCLC is notable for dense clustering of high-level methylation in discrete promoter CpG islands, in a pattern clearly distinct from other lung cancers and strongly correlated with high expression of the E2F target and histone methyltransferase gene EZH2. Pharmacologic inhibition of EZH2 in a SCLC PDX markedly inhibited tumor growth. PMID:25746006

  3. DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2.

    PubMed

    Poirier, J T; Gardner, E E; Connis, N; Moreira, A L; de Stanchina, E; Hann, C L; Rudin, C M

    2015-11-26

    Small cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastasis, rapid development of resistance to chemotherapy and genetic instability. This study profiles DNA methylation in SCLC, patient-derived xenografts (PDX) and cell lines at single-nucleotide resolution. DNA methylation patterns of primary samples are distinct from those of cell lines, whereas PDX maintain a pattern closely consistent with primary samples. Clustering of DNA methylation and gene expression of primary SCLC revealed distinct disease subtypes among histologically indistinguishable primary patient samples with similar genetic alterations. SCLC is notable for dense clustering of high-level methylation in discrete promoter CpG islands, in a pattern clearly distinct from other lung cancers and strongly correlated with high expression of the E2F target and histone methyltransferase gene EZH2. Pharmacologic inhibition of EZH2 in a SCLC PDX markedly inhibited tumor growth.

  4. Correlation between myeloid-derived suppressor cells and S100A8/A9 in tumor and autoimmune diseases.

    PubMed

    Zheng, Ruoting; Chen, Shiyi; Chen, Shenren

    2015-12-01

    Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that constitute an important component of immune regulatory system. Two calcium-binding proteins S100A8 and S100A9 act as important mediators in acute and chronic inflammation. In recent years, many researchers have found that MDSCs and S100A8/A9 operated with one another through a positive feedback loop to promote tumor development and metastasis. However, the correlation between MDSCs and S100A8/A9 in autoimmune diseases (AIDs) remains unknown. In this review, we discussed the co-operation of MDSCs and S100A8/A9 in tumor environment, and also, the role of these two components in AIDs.

  5. Fatty acid composition in serum correlates with that in the liver and non-alcoholic fatty liver disease activity scores in mice fed a high-fat diet.

    PubMed

    Wang, Xing-He; Li, Chun-Yan; Muhammad, Ishfaq; Zhang, Xiu-Ying

    2016-06-01

    In this study, we investigated the correlation between the serum fatty acid composition and hepatic steatosis, inflammation, hepatocellular ballooning scores, and liver fatty acids composition in mice fed a high-fat diet. Livers were collected for non-alcoholic fatty liver disease score analysis. Fatty acid compositions were analysed by gas chromatography. Correlations were determined by Pearson correlation coefficient. Exposed to a high-fat diet, mice developed fatty liver disease with varying severity without fibrosis. The serum fatty acid variation became more severe with prolonged exposure to a high-fat diet. This variation also correlated significantly with the variation in livers, with the types of fatty acids corresponding to liver steatosis, inflammation, and hepatocellular ballooning scores. Results of this study lead to the following hypothesis: the extent of serum fatty acid variation may be a preliminary biomarker of fatty liver disease caused by high-fat intake.

  6. Ivy Sign on Fluid-Attenuated Inversion Recovery Images in Moyamoya Disease: Correlation with Clinical Severity and Old Brain Lesions

    PubMed Central

    Seo, Kwon-Duk; Suh, Sang Hyun; Kim, Yong Bae; Kim, Ji Hwa; Ahn, Sung Jun; Kim, Dong-Seok

    2015-01-01

    Purpose Leptomeningeal collateral, in moyamoya disease (MMD), appears as an ivy sign on fluid-attenuated inversion-recovery (FLAIR) images. There has been little investigation into the relationship between presentation of ivy signs and old brain lesions. We aimed to evaluate clinical significance of ivy signs and whether they correlate with old brain lesions and the severity of clinical symptoms in patients with MMD. Materials and Methods FLAIR images of 83 patients were reviewed. Each cerebral hemisphere was divided into 4 regions and each region was scored based on the prominence of the ivy sign. Total ivy score (TIS) was defined as the sum of the scores from the eight regions and dominant hemispheric ivy sign (DHI) was determined by comparing the ivy scores from each hemisphere. According to the degree of ischemic symptoms, patients were classified into four subgroups: 1) nonspecific symptoms without motor weakness, 2) single transient ischemic attack (TIA), 3) recurrent TIA, or 4) complete stroke. Results TIS was significantly different as follows: 4.86±2.55 in patients with nonspecific symptoms, 5.89±3.10 in patients with single TIA, 9.60±3.98 in patients with recurrent TIA and 8.37±3.39 in patients with complete stroke (p=0.003). TIS associated with old lesions was significantly higher than those not associated with old lesions (9.35±4.22 vs. 7.49±3.37, p=0.032). We found a significant correlation between DHI and motor symptoms (p=0.001). Conclusion Because TIS has a strong tendency with severity of ischemic motor symptom and the presence of old lesions, the ivy sign may be useful in predicting severity of disease progression. PMID:26256975

  7. Correlation between congenital heart disease complicated with pulmonary artery hypertension and circulating endothelial cells as well as endothelin-1

    PubMed Central

    Li, Xiaofei; Qiu, Jun; Pan, Min; Zheng, Dongdong; Su, Yamin; Wei, Meifang; Kong, Xiangqing; Sun, Wei; Zhu, Jiahua

    2015-01-01

    Objective: To investigate changes in the level of circulating endothelial cells (CECs) and endothelin-1 (ET-1) in peripheral venous blood of the patients with congenital heart disease (CHD) complicated with pulmonary artery hypertension (PAH), and research on their effects in the onset and progress of CHD complicated with PAH. Methods: A case-control study including 30 cases of healthy controls, 15 cases of left-to-right shunt CHD without PAH, 26 cases of CHD complicated with mild PAH, and 17 cases of CHD complicated with moderate-severe PAH was performed. We used flow cytometry to measure the percentage of CECs accounting for nucleated cells in whole blood, and enzyme linked immunosorbent assay (ELISA) to measure the level of ET-1 in serum. The differences of above-mentioned biomarkers between different groups were compared. Results: (1) The level of CECs and ET-1in the group of moderate-severe PAH was significantly higher than those in the group of mild PAH and the group of CHD without PAH. Significantly difference was also observed between the level of CECs and ET-1 in the group of mild PAH and those in the group of CHD without PAH and the control group. Meanwhile, the level of CECs and ET-1 in the group of large shunt was significantly higher than those in the group few shunt and few-medium shunt. (2) Strong positive correlations were observed between pulmonary artery systolic pressure and percentage of CECs as well as ET-1 production. Mean pulmonary artery pressure also positively correlated with percentage of CECs as well as ET-1 production. (3) Arterial partial pressure of oxygen as well as arterial oxygen saturation negatively correlated with the level of CECs, whereas the volume of left-to-right shunt positively correlated with the level of ET-1. (4) The level of CECs and ET-1 were positively correlated as well in CHD patients. Conclusions: CHD complicated with PAH is associated with increased CEC counts and ET-1 production. This study suggests that CECs

  8. Slowing of Hippocampal Activity Correlates with Cognitive Decline in Early Onset Alzheimer's Disease. An MEG Study with Virtual Electrodes.

    PubMed

    Engels, Marjolein M A; Hillebrand, Arjan; van der Flier, Wiesje M; Stam, Cornelis J; Scheltens, Philip; van Straaten, Elisabeth C W

    2016-01-01

    Pathology in Alzheimer's disease (AD) starts in the entorhinal cortex and hippocampus. Because of their deep location, activity from these areas is difficult to record with conventional electro- or magnetoencephalography (EEG/MEG). The purpose of this study was to explore hippocampal activity in AD patients and healthy controls using "virtual MEG electrodes". We used resting-state MEG recordings from 27 early onset AD patients [age 60.6 ± 5.4, 12 females, mini-mental state examination (MMSE) range: 19-28] and 26 cognitively healthy age- and gender-matched controls (age 61.8 ± 5.5, 14 females). Activity was reconstructed using beamformer-based virtual electrodes for 78 cortical regions and 6 hippocampal regions. Group differences in peak frequency and relative power in six frequency bands were identified using permutation testing. For the patients, spearman correlations between the MMSE scores and peak frequency or relative power were calculated. Moreover, receiver operator characteristic curves were plotted to estimate the diagnostic accuracy. We found a lower hippocampal peak frequency in AD compared to controls, which, in the patients, correlated positively with MMSE [r(25) = 0.61; p < 0.01] whereas hippocampal relative theta power correlated negatively with MMSE [r(25) = -0.54; p < 0.01]. Cortical peak frequency was also lower in AD in association areas. Furthermore, cortical peak frequency correlated positively with MMSE [r(25) = 0.43; p < 0.05]. In line with this finding, relative theta power was higher in AD across the cortex, and relative alpha and beta power was lower in more circumscribed areas. The average cortical relative theta power was the best discriminator between AD and controls (sensitivity 82%; specificity 81%). Using beamformer-based virtual electrodes, we were able to detect hippocampal activity in AD. In AD, this hippocampal activity is slowed, and correlates better with cognition than the (slowed) activity in cortical areas. On the other

  9. The neural correlates of naming and fluency deficits in Alzheimer’s disease: an FDG-PET study

    PubMed Central

    Melrose, Rebecca J.; Campa, Olivia M.; Harwood, Dylan G.; Osato, Sheryl; Mandelkern, Mark A.; Sultzer, David L.

    2009-01-01

    Summary Objective To examine the neural processes associated with language deficits in Alzheimer’s disease (AD), and in particular to elucidate the correlates of confrontation naming and word retrieval impairments. Methods Sixty patients with probable AD were included. Confrontation naming was assessed using the number of words spontaneously named correctly on the Boston Naming Test. We recorded the number of additional words stated following phonemic cuing. We also assessed phonemic (FAS) and semantic (supermarket items) fluency. We then correlated performance on each measure with resting cortical metabolic activity using FDG-PET images. Results We found that poorer ability to spontaneously name an object was associated with hypometabolism of bilateral inferior temporal lobes. In contrast, when a phonemic cue was provided, successful naming under this condition was associated with higher metabolic activity in bilateral inferior frontal gyrus (IFG), right superior frontal gyrus (SFG), left temporal, and occipital regions. Consistent with these findings, we found that poorer semantic fluency was associated with hypometabolism in regions including both IFG and temporal regions, and poorer phonemic fluency was associated with hypometabolism in only left IFG. Across analyses, measures that required cued retrieval were associated with metabolism in the left IFG, whereas measures taxing semantic knowledge were associated with metabolic rate of left temporal cortex. Conclusions Naming deficits in AD reflect compromise to temporal regions involved in the semantic knowledge network, and frontal regions involved in the controlled retrieval of information from that network. PMID:19296551

  10. Single-nucleotide polymorphisms and haplotypes of non-coding area in the CP gene are correlated with Parkinson's disease.

    PubMed

    Zhao, Na; Xiao, Jianqiu; Zheng, Zhiyong; Fei, Guoqiang; Zhang, Feng; Jin, Lirong; Zhong, Chunjiu

    2015-04-01

    Our previous studies have demonstrated that ceruloplasmin (CP) dysmetabolism is correlated with Parkinson's disease (PD). However, the causes of decreased serum CP levels in PD patients remain to be clarified. This study aimed to explore the potential association between genetic variants of the CP gene and PD. Clinical features, serum CP levels, and the CP gene (both promoter and coding regions) were analyzed in 60 PD patients and 50 controls. A luciferase reporter system was used to investigate the function of promoter single-nucleotide polymorphisms (SNPs). High-density comparative genomic hybridization microarrays were also used to detect large-scale copy-number variations in CP and an additional 47 genes involved in PD and/or copper/iron metabolism. The frequencies of eight SNPs (one intronic SNP and seven promoter SNPs of the CP gene) and their haplotypes were significantly different between PD patients, especially those with lowered serum CP levels, and controls. However, the luciferase reporter system revealed no significant effect of the risk haplotype on promoter activity of the CP gene. Neither these SNPs nor their haplotypes were correlated with the Hoehn and Yahr staging of PD. The results of this study suggest that common genetic variants of CP are associated with PD and further investigation is needed to explore their functions in PD.

  11. Plasma cathepsin D correlates with histological classifications of fatty liver disease in adults and responds to intervention

    PubMed Central

    Walenbergh, Sofie M. A.; Houben, Tom; Rensen, Sander S.; Bieghs, Veerle; Hendrikx, Tim; van Gorp, Patrick J.; Oligschlaeger, Yvonne; Jeurissen, Mike L. J.; Gijbels, Marion J. J.; Buurman, Wim A.; Vreugdenhil, Anita C. E.; Greve, Jan Willem M.; Plat, Jogchum; Hofker, Marten H.; Kalhan, Satish; Pihlajamäki, Jussi; Lindsey, Patrick; Koek, Ger H.; Shiri-Sverdlov, Ronit

    2016-01-01

    Non-alcoholic steatohepatitis (NASH) is characterized by liver lipid accumulation and inflammation. The mechanisms that trigger hepatic inflammation are poorly understood and subsequently, no specific non-invasive markers exist. We previously demonstrated a reduction in the plasma lysosomal enzyme, cathepsin D (CatD), in children with NASH compared to children without NASH. Recent studies have raised the concept that non-alcoholic fatty liver disease (NAFLD) in adults is distinct from children due to a different histological pattern in the liver. Yet, the link between plasma CatD to adult NASH was not examined. In the current manuscript, we investigated whether plasma CatD in adults correlates with NASH development and regression. Biopsies were histologically evaluated for inflammation and NAFLD in three complementary cohorts of adults (total n = 248). CatD and alanine aminotransferase (ALT) were measured in plasma. Opposite to our previous observations with childhood NASH, we observed increased levels of plasma CatD in patients with NASH compared to adults without hepatic inflammation. Furthermore, after surgical intervention, we found a reduction of plasma CatD compared to baseline. Our observations highlight a distinct pathophysiology between NASH in children and adults. The observation that plasma CatD correlated with NASH development and regression is promising for NASH diagnosis. PMID:27922112

  12. Elevated angiopoietin 2 in aqueous of patients with neovascular age related macular degeneration correlates with disease severity at presentation

    PubMed Central

    Ng, Danny S.; Yip, Yolanda W.; Bakthavatsalam, Malini; Chen, Li J.; Ng, Tse K.; Lai, Timothy Y.; Pang, Calvin P.; Brelén, Mårten E.

    2017-01-01

    Angiopoietin 2 (ANG2) is a proangiogenic cytokine which may have an implication in neovascular age related macular degeneration (nAMD). In 24 eyes of 24 subjects presenting with treatment naïve nAMD and 26 eyes of 26 control patients, aqueous humor samples were collected at the time of intervention (intravitreal injection of anti-vascular endothelial growth factor or cataract extraction). Best corrected visual acuity (BCVA) with and central macular thickness (CMT) using optical coherence tomography (OCT) were measured before each injection in the nAMD group. Aqueous cytokine levels were determined by immunoassay using a multiplex array (Quansys Biosciences, Logan, UT). Levels of ANG2 in the aqueous were significantly higher in nAMD patients than those of the control group (p < 0.0001), so were hepatocyte growth factor (HGF), interleukin-8 (IL-8) and tissue inhibitor of metalloproteinase 1 (TIMP 1), all with p < 0.001. ANG2 correlated with worse BCVA (r = 0.44, p-value = 0.027) and greater CMT (r = 0.66, p-value < 0.0001) on optical coherence tomography (OCT). ANG2 is upregulated in patients with nAMD and correlates with severity of disease at presentation. PMID:28345626

  13. Clear correlation of genotype with disease phenotype in very-long-chain acyl-CoA dehydrogenase deficiency.

    PubMed Central

    Andresen, B S; Olpin, S; Poorthuis, B J; Scholte, H R; Vianey-Saban, C; Wanders, R; Ijlst, L; Morris, A; Pourfarzam, M; Bartlett, K; Baumgartner, E R; deKlerk, J B; Schroeder, L D; Corydon, T J; Lund, H; Winter, V; Bross, P; Bolund, L; Gregersen, N

    1999-01-01

    Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the initial rate-limiting step in mitochondrial fatty acid beta-oxidation. VLCAD deficiency is clinically heterogenous, with three major phenotypes: a severe childhood form, with early onset, high mortality, and high incidence of cardiomyopathy; a milder childhood form, with later onset, usually with hypoketotic hypoglycemia as the main presenting feature, low mortality, and rare cardiomyopathy; and an adult form, with isolated skeletal muscle involvement, rhabdomyolysis, and myoglobinuria, usually triggered by exercise or fasting. To examine whether these different phenotypes are due to differences in the VLCAD genotype, we investigated 58 different mutations in 55 unrelated patients representing all known clinical phenotypes and correlated the mutation type with the clinical phenotype. Our results show a clear relationship between the nature of the mutation and the severity of disease. Patients with the severe childhood phenotype have mutations that result in no residual enzyme activity, whereas patients with the milder childhood and adult phenotypes have mutations that may result in residual enzyme activity. This clear genotype-phenotype relationship is in sharp contrast to what has been observed in medium-chain acyl-CoA dehydrogenase deficiency, in which no correlation between genotype and phenotype can be established. PMID:9973285

  14. Correlation of echocardiographic epicardial fat thickness with severity of coronary artery disease in patients with acute myocardial infarction.

    PubMed

    Wang, Tao; Liu, Qiang; Liu, Cuixia; Sun, Ling; Li, Daixu; Liu, Aihua; Jia, Ruyi

    2014-11-01

    The aim of this study was to test the hypotheses that epicardial adipose tissue (EAT) can be a marker of severe coronary artery disease in patients with acute myocardial infarction. Overall, 373 cases who underwent coronary angiography were classified into 2 groups by SYNTAX score: low-score and high-score group. EAT was measured by transthoracic echocardiography. Obtained data were compared using Pearson correlation analyses and univariate and multiple logistic regression analysis. The results showed that EAT in the high-score group was significantly greater than in the normal group (5.6 ± 1.1 vs. 4.1 ± 1.0 mm, P < 0.01). EAT had a positive correlation with SYNTAX score (r = 0.61, P < 0.01). Receiver operating characteristic (ROC) curve analyses showed that EAT could reliably discriminate patients with high SYNTAX score (≥ 33) [AUC: 0.86, 95% confidence interval (CI): 0.822-0.898, P < 0.01]. Multivariate regression analyses showed that EAT was an independent predictor for major in-hospital events. These data showed an association between EAT and SYNTAX score.

  15. δ-Aminolevulinate Dehydratase Activity is Stimulated in a MPTP Mouse Model of Parkinson's Disease: Correlation with Myeloperoxidase Activity.

    PubMed

    Sampaio, Tuane Bazanella; Marcondes Sari, Marcel Henrique; Pesarico, Ana Paula; Nogueira, Cristina Wayne

    2016-09-21

    Myeloperoxidase (MPO) is an inducible heme peroxidase responsive to some stress situations. It is already known that its activity is stimulated in neurodegenerative disorders and in the animal model of parkinson's disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). By contrast, the role of δ-aminolevulinate dehydratase (δ-ALA-D), an essential enzyme for heme synthesis, has not been investigated in the MPTP model. The aim of this study was to investigate the involvement of striatal δ-ALA-D activity in an acute model of PD, induced by MPTP, in C57Bl/6 mice and its correlation with MPO activity. Animals received four MPTP injections (20 mg/kg, i.p.) or saline (vehicle) to induce a PD model. 7 days after MPTP administration, the motor function was evaluated through rotarod and challenging beam tests in mice. Afterward, mice were killed, and the striata were removed for biochemical analyses. MPTP-treated mice showed impairment in motor skills, such as balance and motor coordination. Furthermore, there was a reduction of tyrosine hydroxylase levels in these animals, which characterizes the dopaminergic lesion. Striatal δ-ALA-D activity was stimulated by MPTP, as well as the MPO activity, and a significant positive correlation between δ-ALA-D and MPO activities was also demonstrated. These data suggest that δ-ALA-D activity could be stimulated due to the requirement of heme groups by peroxidases. Therefore, this study demonstrated for the first time the involvement of striatal δ-ALA-D activity in the MPTP model and its correlation with the MPO activity.

  16. Large-scale resting state network correlates of cognitive impairment in Parkinson's disease and related dopaminergic deficits

    PubMed Central

    Lebedev, Alexander V.; Westman, Eric; Simmons, Andrew; Lebedeva, Aleksandra; Siepel, Françoise J.; Pereira, Joana B.; Aarsland, Dag

    2014-01-01

    Cognitive impairment is a common non-motor feature of Parkinson's disease (PD). Understanding the neural mechanisms of this deficit is crucial for the development of efficient methods for treatment monitoring and augmentation of cognitive functions in PD patients. The current study aimed to investigate resting state fMRI correlates of cognitive impairment in PD from a large-scale network perspective, and to assess the impact of dopamine deficiency on these networks. Thirty PD patients with resting state fMRI were included from the Parkinson's Progression Marker Initiative (PPMI) database. Eighteen patients from this sample were also scanned with 123I-FP-CIT SPECT. A standardized neuropsychological battery was administered, evaluating verbal memory, visuospatial, and executive cognitive domains. Image preprocessing was performed using an SPM8-based workflow, obtaining time-series from 90 regions-of-interest (ROIs) defined from the AAL brain atlas. The Brain Connectivity Toolbox (BCT) was used to extract nodal strength from all ROIs, and modularity of the cognitive circuitry determined using the meta-analytical software Neurosynth. Brain-behavior covariance patterns between cognitive functions and nodal strength were estimated using Partial Least Squares. Extracted latent variable (LV) scores were matched with the performances in the three cognitive domains (memory, visuospatial, and executive) and striatal dopamine transporter binding ratios (SBR) using linear modeling. Finally, influence of nigrostriatal dopaminergic deficiency on the modularity of the “cognitive network” was analyzed. For the range of deficits studied, better executive performance was associated with increased dorsal fronto-parietal cortical processing and inhibited subcortical and primary sensory involvement. This profile was also characterized by a relative preservation of nigrostriatal dopaminergic function. The profile associated with better memory performance correlated with increased

  17. Geographic Variation of Chronic Kidney Disease Prevalence: Correlation with the Incidence of Renal Cell Carcinoma or Urothelial Carcinoma?

    PubMed Central

    Yap, Yit-Sheung; Chuang, Kai-Wen; Chiang, Chun-Ju; Chuang, Hung-Yi; Lu, Sheng-Nan

    2015-01-01

    Background. The aim of this study is to evaluate whether geographic variations in the prevalence of late-stage chronic kidney disease (CKD) exist and are associated with incidence rates of renal cell carcinoma (RCC), upper tract urothelial carcinoma (UTUC), or lower tract urothelial carcinoma (LTUC). Methods. Prevalence rates of late-stage CKD for 366 townships (n > 30) in Taiwan were calculated for 1,518,241 and 1,645,151 subjects aged 40 years or older in years 2010 and 2009, respectively. Late-stage CKD prevalence in year 2010 was used as a training set and its age-adjusted standardized morbidity rates (ASMR) were divided into three groups as defined <1.76%, 1.76% ≤ ASMR < 2.64%, and ≥2.64%, respectively. Year 2009, defined as the validation set, was used to validate the results. Results. The ASMR of late-stage CKD in years 2010 and 2009 were 1.76%, and 2.09%, respectively. Geographic variations were observed, with notably higher rates of disease in areas of the central, southwestern mountainside, and southeastern seaboard. There were no significant differences among different combined risk groups of RCC, UTUC, and LTUC incidence. Conclusion. The substantial geographic variations in the prevalence of late-stage CKD exist, but are not correlated with RCC, UTUC, or LTUC incidence. PMID:26605329

  18. Altered Fecal Microbiota Correlates with Liver Biochemistry in Nonobese Patients with Non-alcoholic Fatty Liver Disease

    PubMed Central

    Wang, Baohong; Jiang, Xiangyang; Cao, Min; Ge, Jianping; Bao, Qiongling; Tang, Lingling; Chen, Yu; Li, Lanjuan

    2016-01-01

    Increasing evidence suggests a role of intestinal dysbiosis in obesity and non-alcoholic fatty liver disease (NAFLD). But it remains unknown in nonobese NAFLD. This prospective, cross-sectional study sought to characterize differences in fecal microbiota between nonobese adult individuals with and without NAFLD and their potential association with metabolic markers of disease progression. A total of 126 nonobese subjects were enrolled: 43 NAFLD and 83 healthy controls (HC). The microbial community was profiled by denaturing gradient gel electrophoresis and examined by 454 pyrosequencing of the 16S ribosomal RNA V3 region. Lower diversity and a phylum-level change in the fecal microbiome were found in NAFLD. Compared with HC, patients had 20% more phylum Bacteroidetes (p = 0.005) and 24% less Firmicutes (p = 0.002). Within Firmicutes, four families and their 8 genera, which were short-chain fatty acids-producing and 7α-dehydroxylating bacteria, were significantly decreased. Moreover, Gram-negative (G−) bacteria were prevalent in NAFLD (p = 0.008). Furthermore, a significant correlation with metabolic markers was revealed for disturbed microbiota in NAFLD. This novel study indicated that intestinal dysbiosis was associated with nonobese NAFLD and might increase the risk of NAFLD progression. PMID:27550547

  19. Intra-epidemic evolutionary dynamics of a Dengue virus type 1 population reveal mutant spectra that correlate with disease transmission

    PubMed Central

    Hapuarachchi, Hapuarachchige Chanditha; Koo, Carmen; Kek, Relus; Xu, Helen; Lai, Yee Ling; Liu, Lilac; Kok, Suet Yheng; Shi, Yuan; Chuen, Raphael Lee Tze; Lee, Kim-Sung; Maurer-Stroh, Sebastian; Ng, Lee Ching

    2016-01-01

    Dengue virus (DENV) is currently the most prevalent mosquito-borne viral pathogen. DENVs naturally exist as highly heterogeneous populations. Even though the descriptions on DENV diversity are plentiful, only a few studies have narrated the dynamics of intra-epidemic virus diversity at a fine scale. Such accounts are important to decipher the reciprocal relationship between viral evolutionary dynamics and disease transmission that shape dengue epidemiology. In the current study, we present a micro-scale genetic analysis of a monophyletic lineage of DENV-1 genotype III (epidemic lineage) detected from November 2012 to May 2014. The lineage was involved in an unprecedented dengue epidemic in Singapore during 2013–2014. Our findings showed that the epidemic lineage was an ensemble of mutants (variants) originated from an initial mixed viral population. The composition of mutant spectrum was dynamic and positively correlated with case load. The close interaction between viral evolution and transmission intensity indicated that tracking genetic diversity through time is potentially a useful tool to infer DENV transmission dynamics and thereby, to assess the epidemic risk in a disease control perspective. Moreover, such information is salient to understand the viral basis of clinical outcome and immune response variations that is imperative to effective vaccine design. PMID:26940650

  20. Characteristic laryngoscopic findings in Parkinson's disease patients after subthalamic nucleus deep brain stimulation and its correlation with voice disorder.

    PubMed

    Tsuboi, Takashi; Watanabe, Hirohisa; Tanaka, Yasuhiro; Ohdake, Reiko; Yoneyama, Noritaka; Hara, Kazuhiro; Ito, Mizuki; Hirayama, Masaaki; Yamamoto, Masahiko; Fujimoto, Yasushi; Kajita, Yasukazu; Wakabayashi, Toshihiko; Sobue, Gen

    2015-12-01

    Speech and voice disorders are one of the most common adverse effects in Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS). However, the pathophysiology of voice and laryngeal dysfunction after STN-DBS remains unclear. We assessed 47 PD patients (22 treated with bilateral STN-DBS (PD-DBS) and 25 treated medically (PD-Med); all patients in both groups matched by age, sex, disease duration, and motor and cognitive function) using the objective and subjective voice assessment batteries (GRBAS scale and Voice Handicap Index), and laryngoscopy. Laryngoscopic examinations revealed that PD-DBS patients showed a significantly higher incidence of incomplete glottal closure (77 vs 48 %; p = 0.039), hyperadduction of the false vocal folds (73 vs 44 %; p = 0.047), anteroposterior hypercompression (50 vs 20 %; p = 0.030) and asymmetrical glottal movement (50 vs 16 %; p = 0.002) than PD-Med patients. On- and off-stimulation assessment revealed that STN-DBS could induce or aggravate incomplete glottal closure, hyperadduction of the false vocal folds, anteroposterior hypercompression, and asymmetrical glottal movement. Incomplete glottal closure and hyperadduction of the false vocal folds significantly correlated with breathiness and strained voice, respectively (r = 0.590 and 0.539). We should adjust patients' DBS settings in consideration of voice and laryngeal functions as well as motor function.

  1. CD39 Expression on T Lymphocytes Correlates With Severity of Disease in Patients With Chronic Lymphocytic Leukemia

    PubMed Central

    Pulte, Dianne; Furman, Richard R.; Broekman, M. Johan; Drosopoulos, Joan H. F.; Ballard, Harold S.; Olson, Kim E.; Kizer, Jorge R.; Marcus, Aaron J.

    2012-01-01

    Introduction Chronic lymphocytic leukemia (CLL) is a B-cell disorder, but it is also associated with abnormalities in T-lymphocyte function. In this study we examine changes in T-lymphocyte CD39 and CD73 expression in patients with CLL. Methods Blood samples were drawn from 34 patients with CLL and 31 controls. The cells were stained for CD3, CD4, CD8, CD19, CD39, and CD73 and analyzed by flow cytometry. Results Overall, patients with CLL had a higher percentage of CD39+ T lymphocytes than did controls. The percentage of cells expressing CD39 was higher in both CD4+ cells and CD8+ cells. Higher CD3/CD39 expression was associated with a later disease stage. No correlations between T-lymphocyte CD39 levels and CD38 or Zap-70 expression were observed. In contrast, the percentage of T lymphocytes and B lymphocytes that expressed CD73 was decreased in patients with CLL. Average B-lymphocyte CD73 expression was decreased in CLL because the majority of CLL clones were CD73. However a minority of CLL clones were CD73+, and patients with CD73+ clones tended to have earlier stage disease. Conclusion T-lymphocyte CD39 and CD73 expression may be useful prognostic markers in patients with CLL. Expression of CD73 on the malignant cell population in CLL may be a marker of better prognosis. PMID:21816376

  2. Correlation of Vitamin E, Uric Acid and Diet Composition with Histologic Features of Pediatric Nonalcoholic Fatty Liver Disease

    PubMed Central

    Vos, Miriam B.; Colvin, Ryan; Belt, Patricia; Molleston, Jean P.; Murray, Karen F.; Rosenthal, Philip; Schwimmer, Jeffrey; Tonascia, James; Unalp, Aynur; Lavine, Joel E.

    2011-01-01

    Objectives Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children in the United States. Although changes in diet are often recommended to improve NAFLD, little is known regarding diet influence on histologic features of the disease. Methods This was a prospective, cross-sectional registry based study. Children (n=149) enrolled in the multi-center NASH Clinical Research Network had demographic, anthropometric, clinical, laboratory and histology data obtained, including the Block Brief Food Questionnaire. Subjects were grouped by presence or absence of steatohepatitis and grades of histologic features according to NASH-CRN criteria. Results No significant differences were found between children with steatosis compared to steatohepatitis for fraction of calories from fat, carbohydrates, and protein. Sugar sweetened beverage consumption was low and did not correlate with histologic features, although uric acid, a surrogate marker for fructose intake, was significantly increased in those with definite NASH (p=.008). For all groups, vitamin E consumption was insufficient compared to the recommended daily allowance. Median consumption of vitamin E was lower in children with higher grade of steatosis (8.4 vs 6.1 vs 6.9 for grade I, II and III respectively, p = .05). Those consuming less vitamin C had increased ballooning degeneration (p = 0.05). Conclusions Children with NAFLD have a diet that is insufficient in vitamin E and this may contribute to the pathophysiology of NAFLD. In children with NAFLD, reported sugar sweetened beverage consumption is low; however uric acid, which may reflect total fructose consumption, was significantly associated with NASH and should be further evaluated. PMID:22197855

  3. Hepatocellular carcinoma in chronic HBV-HCV co-infection is correlated to fibrosis and disease duration.

    PubMed

    Zampino, Rosa; Pisaturo, Maria A; Cirillo, Grazia; Marrone, Aldo; Macera, Margherita; Rinaldi, Luca; Stanzione, Maria; Durante-Mangoni, Emanuele; Gentile, Ivan; Sagnelli, Evangelista; Signoriello, Giuseppe; Miraglia Del Giudice, Emanuele; Adinolfi, Luigi E; Coppola, Nicola

    2015-01-01

    Hepatocellular carcinoma (HCC) is a development of severe liver disease frequently due to HBV and/or HCV infection. The aim of this retrospective study was to evaluate the development of HCC in patients with HBV-HCV chronic infection compared with patients with single HBV or HCV infection and the viral and host factors correlated to HCC in co-infected patients. We studied 268 patients with histology proven chronic hepatitis: 56 had HBV-HCV co-infection (HBV-HCV group), 46 had HBV infection (HBV group) and 166 had HCV infection (HCV group). Patients were followed up for at least 3 years. Viral and host factors were studied. HCC was more frequent in HBV-HCV group (14%) compared with HBV (2%, p = 0.006) and HCV monoinfected (4%, p = 0.006). The Mantel-Haenszel test used to investigate the relationship between HBV-HCV co-infection and development of HCC indicated an association between development of HCC and HBV-HCV co-infection (p < 0.001). In the HBV-HCV group, patients with HCC were significantly older (p = 0.000), had longer disease duration (p = 0.001), higher blood glucose levels (p = 0.001), lower levels of steatosis (p = 0.02), higher levels of fibrosis (p = 0.000), higher HCV RNA (p = 0.01) than those without HCC. ALT, lipid profile, PNPLA3 variant distribution and HBV viral load did not differ among co-infected patients with or without HCC. In conclusion HCC was more frequent in our patients with HBV-HCV co-infection, than in those with HBV or HCV mono-infection; possible associated risk factors for HCC development seem a long duration of disease, high levels of fibrosis and carbohydrate intolerance.

  4. Correlation between cognitive impairment and the Rey auditory-verbal learning test in a population with Alzheimer disease.

    PubMed

    Barzotti, T; Gargiulo, A; Marotta, M G; Tedeschi, G; Zannino, G; Guglielmi, S; Dell'Armi, A; Ettorre, E; Marigliano, V

    2004-01-01

    Patients affected by Alzheimer disease (AD) need an accurate diagnosis, to the extent allowing us to find the best therapy or polytherapy, in order to take under control their cognitive impairment. In our Alzheimer Evaluation Units (from the Italian name abbreviated: UVA), the patients undergo a multidimensional evaluation, which can address us towards a proper diagnosis and of other weakening, or even dementia-related diseases. The patients are also subject to neuropsychometric and neuropsychological evaluations, allowing a more focused analysis on cognitive impairments. Among the tests, we use the Rey auditory-verbal learning test (RAVLT), evaluating the patient's verbal memory. A list of 15 words is read to each patient. N the first part of the test, the clinician repeats 5 times such a list. the patient is hen asked, at the end of every repetition, to tell all words he/she remembers. This part is useful to evaluate the immediate recall (IR) ability. The score, i.e., the total number of recalled words, ranges from 0 to 75. After 15 minutes, the delayed recall (DR) ability is evaluated: the patient is newly asked to repeat as many words as he can recall from the list. The score for this part ranges from 0 to 15 minutes. The score is corrected of rage and education, with a cut-off of 28.5 for IR and 4.7 for DR. We made a survey with the purpose of deciding if there was a correlation between cognitive impairment and verbal memory lack, whose deficiency appears earlier in AD. To this aim, we selected several patients with AD, diagnosed during the period between September 2002 and February 2003. We only considered those patients whose AD was not associated with other weakening diseases, and whose clinical dementia rating scale (CDR) score was between 0.5-2.0. A sample of 35 individuals (11 men and 24 women) could be obtained. A meaningful correlation was observed between CDR and IR (r = -0.725, p < 0.01), as well as between CDR and DR (r = -0.470; p < 0.05). Such a

  5. Southern leaf blight disease severity is correlated with decreased maize leaf epiphytic bacterial species richness and the phyllosphere bacterial diversity decline is enhanced by nitrogen fertilization.

    PubMed

    Manching, Heather C; Balint-Kurti, Peter J; Stapleton, Ann E

    2014-01-01

    Plant leaves are inhabited by a diverse group of microorganisms that are important contributors to optimal growth. Biotic and abiotic effects on plant growth are usually studied in controlled settings examining response to variation in single factors and in field settings with large numbers of variables. Multi-factor experiments with combinations of stresses bridge this gap, increasing our understanding of the genotype-environment-phenotype functional map for the host plant and the affiliated epiphytic community. The maize inbred B73 was exposed to single and combination abiotic and the biotic stress treatments: low nitrogen fertilizer and high levels of infection with southern leaf blight (causal agent Cochliobolus heterostrophus). Microbial epiphyte samples were collected at the vegetative early-season phase and species composition was determined using 16S ribosomal intergenic spacer analysis. Plant traits and level of southern leaf blight disease were measured late-season. Bacterial diversity was different among stress treatment groups (P < 0.001). Lower species richness-alpha diversity-was correlated with increased severity of southern leaf blight disease when disease pressure was high. Nitrogen fertilization intensified the decline in bacterial alpha diversity. While no single bacterial ribotype was consistently associated with disease severity, small sets of ribotypes were good predictors of disease levels. Difference in leaf bacterial-epiphyte diversity early in the season were correlated with plant disease severity, supporting further tests of microbial epiphyte-disease correlations for use in predicting disease progression.

  6. Southern leaf blight disease severity is correlated with decreased maize leaf epiphytic bacterial species richness and the phyllosphere bacterial diversity decline is enhanced by nitrogen fertilization

    PubMed Central

    Manching, Heather C.; Balint-Kurti, Peter J.; Stapleton, Ann E.

    2014-01-01

    Plant leaves are inhabited by a diverse group of microorganisms that are important contributors to optimal growth. Biotic and abiotic effects on plant growth are usually studied in controlled settings examining response to variation in single factors and in field settings with large numbers of variables. Multi-factor experiments with combinations of stresses bridge this gap, increasing our understanding of the genotype-environment-phenotype functional map for the host plant and the affiliated epiphytic community. The maize inbred B73 was exposed to single and combination abiotic and the biotic stress treatments: low nitrogen fertilizer and high levels of infection with southern leaf blight (causal agent Cochliobolus heterostrophus). Microbial epiphyte samples were collected at the vegetative early-season phase and species composition was determined using 16S ribosomal intergenic spacer analysis. Plant traits and level of southern leaf blight disease were measured late-season. Bacterial diversity was different among stress treatment groups (P < 0.001). Lower species richness—alpha diversity—was correlated with increased severity of southern leaf blight disease when disease pressure was high. Nitrogen fertilization intensified the decline in bacterial alpha diversity. While no single bacterial ribotype was consistently associated with disease severity, small sets of ribotypes were good predictors of disease levels. Difference in leaf bacterial-epiphyte diversity early in the season were correlated with plant disease severity, supporting further tests of microbial epiphyte-disease correlations for use in predicting disease progression. PMID:25177328

  7. Postoperative executive function in adult moyamoya disease: a preliminary study of its functional anatomy and behavioral correlates.

    PubMed

    Lei, Yu; Li, Yan-Jiang; Guo, Qi-Hao; Liu, Xing-Dang; Liu, Zhuang; Ni, Wei; Su, Jia-Bin; Yang, Heng; Jiang, Han-Qiang; Xu, Bin; Gu, Yu-Xiang; Mao, Ying

    2017-02-01

    OBJECTIVE Chronic frontal hemodynamic disturbances are associated with executive dysfunction in adult patients with moyamoya disease (MMD). However, the impact of surgical revascularization on executive dysfunction and its underlying mechanism remains unclear. The aim of the present study was to examine the postoperative radiological correlates of cognitive improvement and thereby explore its underlying mechanism. METHODS Fourteen patients who met the inclusion criteria were identified at Huashan Hospital, were operated on, and were successfully followed up for 6 months. Postoperative changes in cortical perfusion and regional amplitude of low-frequency fluctuations (ALFF) were examined by SPECT and resting-state functional MRI, respectively. Executive function was evaluated by 2 tests (Trail Making Test Part B and the summation of executive subtests of Memory and Executive Screening [MES-EX]). Follow-up neuropsychological outcomes were then correlated with radiological changes to identify nodes functioning as leading contributors to postoperative executive outcomes. RESULTS All patients underwent successful unilateral bypass procedures, with some operations performed on the left side and some on the right side. At the 6-month follow-up, the baseline and follow-up test scores for the different sides did not differ significantly. The group with good collaterals (Matsushima Grade A, 9 patients) exhibited significantly increased postoperative perfusion (change in [△] hemodynamics) in bilateral frontal (left, p = 0.009; right, p = 0.003) and left parietal lobe (p = 0.014). The Spearman's correlation test suggested that only the right frontal lobe exhibited significant positive postoperative radiological correlates with cognitive performance (△MES-EX vs △hemodynamics, r = 0.620, p = 0.018; △MES-EX vs △ALFF, r = 0.676, p = 0.008; △hemodynamics vs △ALFF, r = 0.547, p = 0.043). Subsequent regional ALFF analysis revealed that the right dorsolateral prefrontal

  8. Human papillomavirus infection in Bowen disease: negative p53 expression, not p16(INK4a) overexpression, is correlated with human papillomavirus-associated Bowen disease.

    PubMed

    Murao, Kazutoshi; Yoshioka, Rika; Kubo, Yoshiaki

    2014-10-01

    Genital Bowen disease (BD) has been linked to the high-risk types of human papillomavirus (HPV) infection. Recently, it has been recognized that HPV also can be associated with extragenital BD. HPV oncoproteins E6 and E7 interfere with the function of p53 and pRb, respectively, leading carcinogenesis. p16(INK4a) overexpression induced by inactivation of pRb is recognized as a surrogate marker for HPV-associated cervical cancer. In this study, we examined the presence of HPV DNA in 142 BD lesions by polymerase chain reaction (PCR), and determined the type of HPV by PCR restriction fragment length polymorphism or direct DNA sequencing. HPV DNA was detected in 66.7% of genital BD and 8.3% of extragenital BD. The types of HPV detected were HPV types 6, 16, 33, 52, 56, 58 and 59. We also investigated the expression of p16(INK4a) , pRb and p53 by immunohistochemistry. Positive expression was detected in 88.6% for p16(INK4a) , 25.2% for pRb, and 63.8% for p53. There was no significant difference in p16(INK4a) and pRb expression between HPV-positive and -negative BD. However, a strong correlation of HPV positivity with p53 negativity was found. A total of 66.7% of HPV-positive BD showed no p53 expression, whereas the corresponding rate was 32.8% of HPV-negative BD. This study demonstrated that HPV can participate in the development of BD, not only in the genital lesion, but also in extragenital lesion. p16(INK) (4a) overexpression is not a marker for HPV infection in BD. Instead, negative p53 expression is correlated with HPV-associated BD.

  9. Feline heartworm disease: correlations of clinical signs, serology, and other diagnostics--results of a multicenter study.

    PubMed

    Dillon, A R; Brawner, A R; Robertson-Plouch, C K; Guerrero, J

    2000-01-01

    In cooperation with 15 practices in Florida, South Carolina, Tennessee, and Texas, data were collected on 215 cats with signs consistent with feline heartworm disease (FHD). Cats included in the study were over 6 months of age and presented with primary complaints of coughing or dyspnea, vomiting unrelated to eating, or acute death. Detailed signalment, thoracic radiographs, CBC, Knott or DIFIL test, DiroCHEK antigen test (Ag), and antibody (Ab) tests performed by Animal Diagnostics (AD) and Heska Corp (HC) were collected on each cat. Any cat that had positive antibody or antigen tests, and any cat with radiographic signs suggestive of FHD was scheduled for recheck examinations at 30 to 45 days and/or 60 to 90 days after initial presentation. This study was designed to identify cats with concurrent or previous FHD, and to better characterize the presentation of this disease by following their progress. Of the 215 cats, 94 (44%) were Ab positive based on one or both tests. This indicated that the cat had been successfully infected with third-stage heartworm larvae and those larvae had developed to at least the fourth stage. Of the Ab-positive cats, 23/94 (24%) presented with vomiting; 39/94 (41%) presented with respiratory signs; and 27/94 (29%) had vomiting and respiratory signs. Discordant results between the AD and HC antibody tests occurred, with the AD test detecting a higher number of antibody-positive cats. When comparing results of these Ab tests, no correlation was seen between the intensity of Ab level measured by the two tests, suggesting that different Ab is detected. One cat that died acutely with signs associated with FHD had relatively low Ab detected on both tests but had a positive DiroCHEK antigen test. No correlation between the level of antibody and the severity of clinical signs or radiographic pattern was found. Eleven cars were DiroCHEK Ag positive on initial presentation. Of the Ag-positive cats, 2 were AD negative and 3 were HC negative. One

  10. Atrial natriuretic factor in chronic obstructive lung disease with pulmonary hypertension. Physiological correlates and response to peptide infusion.

    PubMed Central

    Adnot, S; Andrivet, P; Chabrier, P E; Piquet, J; Plas, P; Braquet, P; Roudot-Thoraval, F; Brun-Buisson, C

    1989-01-01

    To investigate the physiological role of atrial natriuretic factor (ANF) in patients with hypoxic pulmonary hypertension secondary to chronic obstructive lung disease (COLD), we infused synthetic alpha-human ANF in seven such patients, and investigated the physiological correlates to circulating peptide levels in 24 patients with COLD. ANF infusion, at incremental rates of 0.01, 0.03, and 0.1 micrograms/kg.min, increased basal plasma immunoreactive (ir) ANF (136 +/- 38 pg/ml) by 3-, 10-, and 26-fold, respectively, and reduced pulmonary artery pressure (from 33 +/- 3 to 25 +/- 2 mmHg, P less than 0.001) and systemic arterial pressure (from 88 +/- 4 to 79 +/- 4 mmHg, P less than 0.001) in a dose-related fashion. Cardiac index increased by 13.5% (P less than 0.01) while heart rate was unchanged. Cardiac filling pressures decreased at 0.1 micrograms/kg.min ANF. Pulmonary and systemic vascular resistance fell by 37% (P less than 0.001) and 19% (P less than 0.001), respectively. Arterial oxygenation was impaired during ANF infusion, suggesting partial reversal of hypoxic pulmonary vasoconstriction. Plasma renin activity remained unchanged but aldosterone fell by 44% (P less than 0.01). The levels of plasma irANF in 24 patients correlated directly with the degree of hemoconcentration (r = 0.67, P less than 0.001), respiratory acidosis (r = -0.65, P less than 0.001), and pulmonary hypertension (r = 0.52, P less than 0.01). The results suggest that ANF may serve as a potent pulmonary vasodilator involved in the circulatory homeostasis of patients with COLD. PMID:2522105

  11. Expression of hepatic Fibroblast Growth Factor 19 is enhanced in Primary Biliary Cirrhosis and correlates with severity of the disease.

    PubMed

    Wunsch, Ewa; Milkiewicz, Małgorzata; Wasik, Urszula; Trottier, Jocelyn; Kempińska-Podhorodecka, Agnieszka; Elias, Elwyn; Barbier, Olivier; Milkiewicz, Piotr

    2015-08-21

    Cholestasis induces adaptive mechanisms protecting the liver against bile acids (BA) toxicity including modulation of BA synthesis. Whether fibroblast growth factor 19 (FGF19) or farnesoid X receptor (FXR) dependent signaling are involved in the regulation of BA homeostasis in primary biliary cirrhosis (PBC) remains unknown. Here we analyzed hepatic expression of FGF19 and other genes relevant to the adaptive response to cholestasis in tissues from non-cirrhotic (n = 24) and cirrhotic (n = 21) patients along with control tissues (n = 21). Moreover we searched for relationships between serum FGF19 and laboratory/clinical findings in 51 patients. Hepatic FGF19 mRNA expression was increased in non-cirrhotic and cirrhotic tissues (9-fold,p = 0.01; 69-fold,p < 0.0001, respectively). Protein levels of FGF19, FGF receptor 4, FXR and short heterodimer partner were increased in cirrhotic livers (9-fold, p < 0.001; 3.5-fold,p = 0.007; 2.4-fold,p < 0.0001; 2.8-fold,p < 0.0001 vs controls, respectively) which was accompanied by down-regulation of CYP7A1 (50% reduction, p = 0.006). Serum and liver levels of FGF19 correlated with worse liver biochemistry, BAs, quality of life and Mayo Risk Score. Serum FGF19 was elevated in UDCA non-responders. We conclude that PBC induces characteristic changes in liver expression of BAs synthesis regulatory molecules. FGF19 correlates with severity of liver disease and can potentially serve as an indicator of chronic cholestatic liver injury.

  12. Uncovering Molecular Biomarkers That Correlate Cognitive Decline with the Changes of Hippocampus' Gene Expression Profiles in Alzheimer's Disease

    PubMed Central

    Gómez Ravetti, Martín; Rosso, Osvaldo A.; Berretta, Regina; Moscato, Pablo

    2010-01-01

    Background Alzheimer's disease (AD) is characterized by a neurodegenerative progression that alters cognition. On a phenotypical level, cognition is evaluated by means of the MiniMental State Examination (MMSE) and the post-morten examination of Neurofibrillary Tangle count (NFT) helps to confirm an AD diagnostic. The MMSE evaluates different aspects of cognition including orientation, short-term memory (retention and recall), attention and language. As there is a normal cognitive decline with aging, and death is the final state on which NFT can be counted, the identification of brain gene expression biomarkers from these phenotypical measures has been elusive. Methodology/Principal Findings We have reanalysed a microarray dataset contributed in 2004 by Blalock et al. of 31 samples corresponding to hippocampus gene expression from 22 AD subjects of varying degree of severity and 9 controls. Instead of only relying on correlations of gene expression with the associated MMSE and NFT measures, and by using modern bioinformatics methods based on information theory and combinatorial optimization, we uncovered a 1,372-probe gene expression signature that presents a high-consensus with established markers of progression in AD. The signature reveals alterations in calcium, insulin, phosphatidylinositol and wnt-signalling. Among the most correlated gene probes with AD severity we found those linked to synaptic function, neurofilament bundle assembly and neuronal plasticity. Conclusions/Significance A transcription factors analysis of 1,372-probe signature reveals significant associations with the EGR/KROX family of proteins, MAZ, and E2F1. The gene homologous of EGR1, zif268, Egr-1 or Zenk, together with other members of the EGR family, are consolidating a key role in the neuronal plasticity in the brain. These results indicate a degree of commonality between putative genes involved in AD and prion-induced neurodegenerative processes that warrants further investigation

  13. Angiographic correlations of patients with small vessel disease diagnosed by adenosine-stress cardiac magnetic resonance imaging.

    PubMed

    Pilz, Guenter; Klos, Markus; Ali, Eman; Hoefling, Berthold; Scheck, Roland; Bernhardt, Peter

    2008-01-31

    Cardiac magnetic resonance imaging (CMR) with adenosine-stress myocardial perfusion is gaining importance for the detection and quantification of coronary artery disease (CAD). However, there is little knowledge about patients with CMR-detected ischemia, but having no relevant stenosis as seen on coronary angiography (CA). The aims of our study were to characterize these patients by CMR and CA and evaluate correlations and potential reasons for the ischemic findings. 73 patients with an indication for CA were first scanned on a 1.5T whole-body CMR-scanner including adenosine-stress first-pass perfusion. The images were analyzed by two independent investigators for myocardial perfusion which was classified as subendocardial ischemia (n = 22), no perfusion deficit (n = 27, control 1), or more than subendocardial ischemia (n = 24, control 2). All patients underwent CA, and a highly significant correlation between the classification of CMR perfusion deficit and the degree of coronary luminal narrowing was found. For quantification of coronary blood flow, corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (TFC) was evaluated for the left anterior descending (LAD), circumflex (LCX) and right coronary artery (RCA). The main result was that corrected TFC in all coronaries was significantly increased in study patients compared to both control 1 and to control 2 patients. Study patients had hypertension or diabetes more often than control 1 patients. In conclusion, patients with CMR detected subendocardial ischemia have prolonged coronary blood flow. In connection with normal resting flow values in CAD, this supports the hypothesis of underlying coronary microvascular impairment. CMR stress perfusion differentiates non-invasively between this entity and relevant CAD.

  14. Correlations between immunogenicity, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab.

    PubMed

    Benucci, Maurizio; Meacci, Francesca; Grossi, Valentina; Infantino, Maria; Manfredi, Mariangela; Bellio, Emanuele; Bellio, Valerio; Li Gobbi, Francesca; Bazzichi, Laura; Moscato, Paolo; Caputo, Dario; Saviola, Gianantonio; Talotta, Rossella; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola

    2016-01-01

    The aim of this study was to evaluate the real-life immunogenicity of anti-drug antibodies, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab (TCZ). We evaluated 126 TCZ-treated patients with rheumatoid arthritis (16 males and 110 females; mean age 59±12 years, range 26-83; mean disease duration 11±5 years) with inadequate 12-week response to any synthetic and biological disease-modifying anti-rheumatic drugs, in a retrospective analysis. One-hundred and seven patients were treated with methotrexate mean dose 12.6±1.3 mg/week in combination with TCZ, 13 received TCZ monotherapy, and six received leflunomide 20 mg/day plus TCZ; all patients were treated with prednisone mean dose 6.4±1.2 mg/day. They had a 28-joint Disease Activity Score (DAS28) of >3.2, an erythrocyte sedimentation rate (ESR) of >30 mm/hour, and CRP levels of >1.0 mg/dL. We evaluated at baseline and after 6 months of treatment: DAS28; rheumatoid factor (RF) IgM, IgA, and IgG; anti-citrullinated peptide antibody; ESR; CRP; TNF-α; and IL-6. TCZ and anti-TCZ antibodies were detected using LISA-TRACKER Duo TCZ. TCZ levels of <10 µg/mL were considered low and >10 µg/mL high. After 6 months of treatment only one patient was positive for anti-TCZ antibodies. There were correlations between DAS28, ESR, and CRP and IL-6 levels in all patients. Comparison of the 84 patients with TCZ levels of <10 µg/mL and the 42 with TCZ levels of >10 µg/mL showed the following differences: DAS28: 3.09±1.32 vs 2.78±1.32, P=0.0005; ESR: 27±14.8 vs 14±12 mm/hour, P=0.0001; CRP: 1.47±1.05 vs 0.65±0.80 mg/dL, P=0.0086; TNF-α: 10.2±1.2 vs 9.9±1.1 pg/mL, P=0.999; IL-6: 3.65±4.75 vs 3.62±4.41 pg/mL, P=0.97; anti-citrullinated peptide antibody: 85.2±93.7 vs 86.7±90.3 IU/mL, P=0.94; RF IgM: 72.4±62.7 vs 68.3±61.6 IU/mL, P=0.754; RF IgA: 41.7±36.4 vs 47.8±42.1 U/mL, P=0.449; and RF IgG: 46.4±46.1 vs 59.3±58.2 U/mL, P=0.212. These findings show

  15. Correlations between immunogenicity, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab

    PubMed Central

    Benucci, Maurizio; Meacci, Francesca; Grossi, Valentina; Infantino, Maria; Manfredi, Mariangela; Bellio, Emanuele; Bellio, Valerio; Li Gobbi, Francesca; Bazzichi, Laura; Moscato, Paolo; Caputo, Dario; Saviola, Gianantonio; Talotta, Rossella; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola

    2016-01-01

    The aim of this study was to evaluate the real-life immunogenicity of anti-drug antibodies, drug levels, and disease activity in an Italian cohort of rheumatoid arthritis patients treated with tocilizumab (TCZ). We evaluated 126 TCZ-treated patients with rheumatoid arthritis (16 males and 110 females; mean age 59±12 years, range 26–83; mean disease duration 11±5 years) with inadequate 12-week response to any synthetic and biological disease-modifying anti-rheumatic drugs, in a retrospective analysis. One-hundred and seven patients were treated with methotrexate mean dose 12.6±1.3 mg/week in combination with TCZ, 13 received TCZ monotherapy, and six received leflunomide 20 mg/day plus TCZ; all patients were treated with prednisone mean dose 6.4±1.2 mg/day. They had a 28-joint Disease Activity Score (DAS28) of >3.2, an erythrocyte sedimentation rate (ESR) of >30 mm/hour, and CRP levels of >1.0 mg/dL. We evaluated at baseline and after 6 months of treatment: DAS28; rheumatoid factor (RF) IgM, IgA, and IgG; anti-citrullinated peptide antibody; ESR; CRP; TNF-α; and IL-6. TCZ and anti-TCZ antibodies were detected using LISA-TRACKER Duo TCZ. TCZ levels of <10 µg/mL were considered low and >10 µg/mL high. After 6 months of treatment only one patient was positive for anti-TCZ antibodies. There were correlations between DAS28, ESR, and CRP and IL-6 levels in all patients. Comparison of the 84 patients with TCZ levels of <10 µg/mL and the 42 with TCZ levels of >10 µg/mL showed the following differences: DAS28: 3.09±1.32 vs 2.78±1.32, P=0.0005; ESR: 27±14.8 vs 14±12 mm/hour, P=0.0001; CRP: 1.47±1.05 vs 0.65±0.80 mg/dL, P=0.0086; TNF-α: 10.2±1.2 vs 9.9±1.1 pg/mL, P=0.999; IL-6: 3.65±4.75 vs 3.62±4.41 pg/mL, P=0.97; anti-citrullinated peptide antibody: 85.2±93.7 vs 86.7±90.3 IU/mL, P=0.94; RF IgM: 72.4±62.7 vs 68.3±61.6 IU/mL, P=0.754; RF IgA: 41.7±36.4 vs 47.8±42.1 U/mL, P=0.449; and RF IgG: 46.4±46.1 vs 59.3±58.2 U/mL, P=0.212. These findings show

  16. Asymmetric dimethylarginine but not osteoprotegerin correlates with disease severity in patients with moderate-to-severe psoriasis undergoing anti-tumor necrosis factor-α therapy.

    PubMed

    Pina, Trinitario; Genre, Fernanda; Lopez-Mejias, Raquel; Armesto, Susana; Ubilla, Begoña; Mijares, Veronica; Dierssen-Sotos, Trinidad; Corrales, Alfonso; Gonzalez-Lopez, Marcos A; Gonzalez-Vela, Maria C; Blanco, Ricardo; Hernández, Jose L; Llorca, Javier; Gonzalez-Gay, Miguel A

    2016-04-01

    Patients with psoriasis, in particular those with severe disease, have an increased risk of cardiovascular (CV) events compared with the general population. The aim of the present study is to determine whether correlation between asymmetric dimethylarginine (ADMA) and osteoprotegerin (OPG), two biomarkers associated with CV disease, and disease severity may exist in patients with moderate-to-severe psoriasis. We also aimed to establish if baseline serum levels of these two biomarkers could correlate with the degree of change in the clinical parameters of disease severity following the use of anti-tumor necrosis factor (TNF)-α therapy in these patients. This was a prospective study on a series of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α-adalimumab. Patients with kidney disease, hypertension or body mass index of 35 kg/m(2) or more were excluded. Metabolic and clinical evaluation was performed immediately prior to the onset of treatment and at month 6. Twenty-nine patients were assessed. Unlike OPG, a significant positive correlation between ADMA and resistin serum levels was found at the onset of adalimumab and also after 6 months of biologic therapy. We also observed a positive correlation between the percent of body surface area affected (BSA) and ADMA levels obtained before the onset of adalimumab and a negative correlation between baseline ADMA levels and a 6-month BSA change compared with baseline results. In patients with moderate-to-severe psoriasis, ADMA levels correlate with clinical markers of disease severity.

  17. Autonomic Response to a Visceral Stressor is Dysregulated in Irritable Bowel Syndrome and Correlates with Duration of Disease

    PubMed Central

    Cheng, Paul; Shih, Wendy; Alberto, Melissa; Presson, Angela P.; Licudine, Arlene; Mayer, Emeran A.; Naliboff, Bruce D.; Chang, Lin

    2013-01-01

    Background Previous studies reported altered autonomic nervous system (ANS) responses in IBS at baseline and to colonic balloon distension. This study examined heart rate variability (HRV) and plasma catecholamines as an index of ANS responsiveness in IBS during flexible sigmoidoscopy (FS) and explored associations of HRV with clinical measures. Methods Rome III positive IBS patients and healthy controls completed questionnaires measuring GI and psychological symptoms. HRV measures were calculated using electrocardiogram (ECG) data at rest and during FS. Plasma catecholamines were measured before and after the FS. Linear mixed effects models were used to compare HRV with IBS status and IBS duration across six time points. Significance was assessed at the 0.05 level. Results 36 IBS patients (53% F, mean age 37.89) and 31 controls (58% F, mean age 37.26) participated. After adjusting for age, sex, BMI, and HAD anxiety, IBS patients had a non-significant lower cardiovagal tone (p=0.436) and higher cardiosympathetic balance (p=0.316) at rest. During FS, controls showed a transient increase in cardiosympathetic balance and decrease in cardiovagal tone. However, IBS patients had significantly less cardiosympathetic and cardiovagal responsiveness both leading up to (p=0.003, p=0.005) and following (p=0.001, p=0.001) this stimulus. Those with longer duration of disease had less cardiosympathetic (p=0.014) and cardiovagal (p=0.009) responsiveness than those with shorter duration. No differences in catecholamines between IBS and controls were found. Conclusion IBS demonstrated dysregulated ANS responses to a visceral stressor which could be related to disease duration. Therefore, autonomic dysregulation is an objective physiologic correlate of IBS. PMID:23822743

  18. Differentiation of monocytes into CD1a- dendritic cells correlates with disease progression in HIV-infected patients.

    PubMed

    Sacchi, Alessandra; Cappelli, Giulia; Cairo, Cristiana; Martino, Angelo; Sanarico, Nunzia; D'Offizi, Gianpiero; Pupillo, Leopoldo Paolo; Chenal, Henri; De Libero, Gennaro; Colizzi, Vittorio; Vendetti, Silvia

    2007-12-15

    Monocyte differentiation into dendritic cells (DCs) depends on microenvironmental conditions. In this study, the capacity of human monocytes to differentiate into mature DCs and their ability to induce an antiviral immune response was investigated in HIV-infected patients. In healthy subjects, monocytes differentiate into CD1a+ DCs in the presence of granulocyte macrophage colony-stimulating factor and interleukin (IL)-4 and matured in the presence of lipopolysaccharide. Here, we found that in 30% and 45% of HIV-infected white and African subjects, respectively, monocytes gave rise to a homogeneous CD1a* DC population. In the patients who gave rise only to the CD1a* DCs, this population spontaneously produced IL-10 but not IL-12, and induced a T helper 2-like immune response when cultured with human T cells isolated from cord blood mononuclear cells. In patients with monocytes differentiated into CD1a* DCs, a high percentage of HIV-specific CD4 T cells producing IL-4 were seen in the peripheral blood. Furthermore, differentiation of monocytes into DCs with CD1a* phenotype correlated with low CD4 T-cell counts and high viral loads in HIV-infected subjects. These results suggest that the differentiation of monocytes into CD1a* DCs may be a phenotypic marker associated with progression of the disease.

  19. Expression of decorin in intestinal tissues of mice with inflammatory bowel disease and its correlation with autophagy

    PubMed Central

    Zhao, Huazhou; Xi, Hongqing; Wei, Bo; Cai, Aizhen; Wang, Ting; Wang, Yi; Zhao, Xudong; Song, Yanjing; Chen, Lin

    2016-01-01

    The aim of this study was to investigate the expression of decorin (DCN) in the intestinal tissues of mice with inflammatory bowel disease (IBD) and its correlation with autophagy. The IBD mouse model was created by intrarectal injection of trinitrobenzene sulfonic acid. The pathology of colon tissues of the mice was examined using hematoxylin and eosin staining. Expression of DCN and the proteins associated with autophagy was detected using immunohistochemistry. Normal human colon mucosal epithelial cells (NCM460 cells) were transfected with DCN expression plasmid and the expression of DCN and autophagy-associated proteins was detected by western blot analysis. Cell apoptosis was studied using an Annexin V apoptosis detection assay and intracellular autophagosomes were observed using electron microscopy. The IBD mouse model was successfully established. Thickening, edema and inflammatory cell infiltration of the intestinal wall were observed in the IBD mice. The expression of DCN as well as the autophagy-associated proteins beclin 1 and LC3B, was increased in the intestinal tissues of the IBD mice. Furthermore, in the NCM460 cells transfected with DCN, the expression of beclin 1 and LC3B was upregulated, while p62 expression was downregulated. Intracellular autophagosomes were increased and apoptosis was decreased in the cells with DCN overexpression. Inhibition of autophagy reversed the effects of DCN on apoptosis. Therefore, DCN is able to induce autophagy and protect intestinal cells during the occurrence and development of IBD. PMID:28105121

  20. B-cell-attracting chemokine-1 (BCA-1/CXCL13) in systemic lupus erythematosus, its correlation to disease activity and renal involvement.

    PubMed

    Hafez, Sawsan Said; Saad, Wessam El Sayed; Shedid, Noha Hussien

    2014-01-01

    Systemic lupus erythematosus (SLE) is a prototype of systemic autoimmune disease in which cytokines such as B lymphocyte chemoattractant (BLC or CXCL13) may play important roles in pathogenesis. The aim of our study was to investigate the implications of CXCL13 in SLE diagnosis and its correlation with disease activity and renal involvement. The study included 50 adult female patients with SLE and 30 age-matched female healthy individuals serving as a control group. Patients' Group was further subdivided according to disease activity calculated by SLE Disease Activity Index (SLEDAI). All studied individuals were subjected to assessment of serum CXCL13 by ELISA. A highly significant stepwise progressive increase in CXCL 13 level was recorded through controls, inactive SLE and active disease (P < 0.01). Moreover, it correlated positively with SLEDAI and proteinuria (P < 0.01). At a cut- off level 80 pg/mL, CXCL13 could discriminate active SLE from inactive (AUC = 0.989, sensitivity 100% & specificity 96%). In conclusion, an increased level of CXCL13 is a distinctive feature in SLE. CXCL13 correlates with disease activity and renal involvement.

  1. Beak and feather disease virus: correlation between viral load and clinical signs in wild Cape parrots (Poicepahlus robustus) in South Africa.

    PubMed

    Regnard, Guy L; Boyes, Rutledge S; Martin, Rowan O; Hitzeroth, Inga I; Rybicki, Edward P

    2015-01-01

    Psittacine beak and feather disease (PBFD), the most prevalent viral disease affecting psittacines, is caused by beak and feather disease virus (BFDV). This study assessed viral load using qPCR in a wild Cape parrot population affected by PBFD and compared it to overall physical condition based on clinical signs attributable to PBFD. A significant inverse correlation between viral load and overall physical condition was found, which confirmed that clinical signs may confidently be used to diagnose the relative severity of BFDV infections in wild populations. This is the first assessment of BFDV viral load in a wild psittacine population.

  2. Pattern of disease after murine hepatitis virus strain 3 infection correlates with macrophage activation and not viral replication.

    PubMed Central

    Pope, M; Rotstein, O; Cole, E; Sinclair, S; Parr, R; Cruz, B; Fingerote, R; Chung, S; Gorczynski, R; Fung, L

    1995-01-01

    Murine hepatitis virus strain (MHV-3) produces a strain-dependent pattern of disease which has been used as a model for fulminant viral hepatitis. This study was undertaken to examine whether there was a correlation between macrophage activation and susceptibility or resistance to MHV-3 infection. Peritoneal macrophages were isolated from resistant A/J and susceptible BALB/cJ mice and, following stimulation with MHV-3 or lipopolysaccharide (LPS), analyzed for transcription of mRNA and production of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), mouse fibrinogen-like protein (musfiblp), tissue factor (TF), leukotriene B4, and prostaglandin E2 (PGE2). Macrophages from BALB/cJ mice produced greater amounts of IL-1, TNF-alpha, TGF-beta, leukotriene B4, and musfiblp following MHV-3 infection than macrophages from resistant A/J mice, whereas in response to LPS, equivalent amounts of IL-1, TNF-alpha, TGF-beta, and TF were produced by macrophages from both strains of mice. Levels of mRNA of IL-1, TNF-alpha, and musfiblp were greater and more persistent in BALB/cJ than in A/J macrophages, whereas the levels and kinetics of IL-1, TNF-alpha, and TF mRNA following LPS stimulation were identical in macrophages from both strains of mice. Levels of production of PGE2 by MHV-3-stimulated macrophages from resistant and susceptible mice were equivalent; however, the time course for induction of PGE2, differed, but the total quantity of PGE2 produced was insufficient to inhibit induction of musfiblp, a procoagulant known to correlate with development of fulminant hepatic necrosis in susceptible mice. These results demonstrate marked differences in production of inflammatory mediators to MHV-3 infection in macrophages from resistant A/J and susceptible BALB/cJ mice, which may explain the marked hepatic necrosis and fibrin deposition and account for the lethality of MHV-3 in susceptible mice. PMID:7636967

  3. Amyloid Beta-Mediated Hypomethylation of Heme Oxygenase 1 Correlates with Cognitive Impairment in Alzheimer’s Disease

    PubMed Central

    Sung, Hye Youn; Choi, Byung-Ok; Jeong, Jee Hyang; Kong, Kyoung Ae; Hwang, Jinha; Ahn, Jung-Hyuck

    2016-01-01

    To identify epigenetically regulated genes involved in the pathogenesis of Alzheimer’s disease (AD) we analyzed global mRNA expression and methylation profiles in amyloid precursor protein (APP)-Swedish mutant-expressing AD model cells, H4-sw and selected heme oxygenase-1 (HMOX1), which is associated with pathological features of AD such as neurofibrillary tangles and senile plaques. We examined the epigenetic regulatory mechanism of HMOX1 and its application as a diagnostic and prognostic biomarker for AD. Our results show that HMOX1 mRNA and protein expression was approximately 12.2-fold and 7.9-fold increased in H4-sw cells, respectively. Increased HMOX1 expression was also detected in the brain, particularly the hippocampus, of AD model transgenic mice. However, the methylation of specific CpG sites within its promoter, particularly at CpG located −374 was significantly decreased in H4-sw cells. Treatment of neuroglioma cells with the demethylating agent 5-aza-2′-deoxycytidine resulted in reduced methylation of HMOX1 promoter accompanied by enhanced HMOX1 expression strongly supporting DNA methylation-dependent transcriptional regulation of HMOX1. Toxic Aβ-induced aberrant hypomethylation of HMOX1 at −374 promoter CpG site was correlated with increased HMOX1expression. In addition to neuroglioma cells, we also found Aβ-induced epigenetic regulation of HMOX1 in human T lymphocyte Jurkat cells. We evaluated DNA methylation status of HMOX1 at −374 promoter CpG site in blood samples from AD patients, patients with mild cognitive impairment (MCI), and control individuals using quantitative methylation-specific polymerase chain reaction. We observed lower methylation of HMOX1 at the −374 promoter CpG site in AD patients compared to MCI and control individuals, and a correlation between Mini-Mental State Examination score and demethylation level. Receiver operating characteristics analysis revealed good discrimination of AD patients from MCI patients and

  4. High avidity HSV-1 antibodies correlate with absence of amnestic Mild Cognitive Impairment conversion to Alzheimer's disease.

    PubMed

    Agostini, Simone; Mancuso, Roberta; Baglio, Francesca; Cabinio, Monia; Hernis, Ambra; Costa, Andrea Saul; Calabrese, Elena; Nemni, Raffaello; Clerici, Mario

    2016-11-01

    Amnestic Mild Cognitive Impairment (aMCI) is an alteration in cognitive abilities that can progress to Alzheimer's disease (AD), a condition in which herpes simplex type 1 (HSV-1) infection might play a pathogenetic role. Prognostic indexes capable of predicting aMCI conversion to AD are only partially understood. The objective of the present work is to verify whether HSV-1 immune responses is involved in conversion of aMCI to AD and correlate with grey matter brain morphometry. Two homogeneous groups of individuals who did or did not convert to AD over a 24-months period were selected after retrospective analysis of a cohort of patients with a diagnosis of aMCI. The selection of subjects was based on: a) clinical follow-up; b) neurocognitive evaluation at baseline and after 24months; c) availability of serum and DNA samples at baseline. 36 aMCI individuals, 21 of whom did (aMCI-converters) and 15 of whom did not (aMCI-non-converters) convert to AD, were included in the study. HSV-1 antibody (Ab) titers, avidity index and APOE genotyping were performed in all the enrolled individuals at baseline. Brain magnetic resonance imaging (MRI) by 1.5T scanner results at baseline were available as well in most (29/36) of these individuals. HSV-1-specific Ab titers were increased at baseline in aMCI-non-converters, and the avidity of these Ab was significantly higher in aMCI-non-converter compared to aMCI-converter (p=0.0018). Receiver operating characteristics analysis showed that HSV-1 avidity had a predictive value in distinguishing between aMCI-non-converters and aMCI-converters (p<0.0001). Notably, a positive correlation was detected as well between HSV-1 antibody titers and MRI-evaluated cortical volumes in the left hippocampus and amigdala (pcorr<0.05). In conclusion, stronger HSV-1-specific humoral responses associate with protection against AD conversion and better-preserved cortical volumes. These results reinforce the hypothesis for a role for HSV-1 in the

  5. CD28⁻ CD8⁺ T cells are significantly reduced and correlate with disease duration in juveniles with type 1 diabetes.

    PubMed

    Yarde, Danielle N; Lorenzo-Arteaga, Kristina; Corley, Kevin P; Cabrera, Monina; Sarvetnick, Nora E

    2014-10-01

    Type 1 diabetes (T1D) is a chronic disease caused by autoimmune destruction of insulin-producing pancreatic β-cells. T1D is typically diagnosed in children, but information regarding immune cell subsets in juveniles with T1D is scarce. Therefore, we studied various lymphocytic populations found in the peripheral blood of juveniles with T1D compared to age-matched controls (ages 2-17). One population of interest is the CD28(-) CD8(+) T cell subset, which are late-differentiated cells also described as suppressors. These cells are altered in a number of disease states and have been shown to be reduced in adults with T1D. We found that the proportion of CD28(-) cells within the CD8(+) T cell population is significantly reduced in juvenile type 1 diabetics. Furthermore, this reduction is not correlated with age in T1D juveniles, although a significant negative correlation between proportion CD28(-) CD8(+) T cells and age was observed in the healthy controls. Finally, correlation analysis revealed a significant and negative correlation between the proportion of CD28(-) CD8(+) T cells and T1D disease duration. These findings show that the CD28(-) CD8(+) T cell population is perturbed following onset of disease and may prove to be a valuable marker for monitoring the progression of T1D.

  6. Vascular pathology in Alzheimer disease: correlation of cerebral amyloid angiopathy and arteriosclerosis/lipohyalinosis with cognitive decline.

    PubMed

    Thal, Dietmar Rudolf; Ghebremedhin, Estifanos; Orantes, Mario; Wiestler, Otmar D

    2003-12-01

    Sporadic, late-onset Alzheimer disease (AD) constitutes the most frequent cause of dementia in the elderly population. AD-related pathology is often accompanied by vascular changes. The predominant vascular lesions in AD are cerebral amyloid angiopathy (CAA) and arteriosclerosis/lipohyalinosis (AS/LH). The present study was carried out to examine the coincidence of these small vessel pathologies during the development of cognitive deficits, amyloid beta-protein (A beta) deposition, and neurofibrillary tangle (NFT) formation in sporadic late-onset AD. We correlated the clinical dementia rating (CDR) score, the sequential extension of AD-related A beta deposition into different parts of the brain, and the extension of NFTs to involve more brain regions with the distribution of CAA and AS/LH in 52 human autopsy brains. The extension of CAA and AS/LH to involve different areas of the brain was associated with a rise of CDR scores and an increase in the extension of A beta deposition and NFT generation. AD cases showed a higher number of regions with CAA and AS/LH compared to nondemented patients with AD-related pathology and controls. Moreover, we demonstrated a hierarchical sequence in which the different regions of the brain exhibited CAA and AS/LH-affected vessels, allowing the distinction of 3 stages in the development of CAA and AS/LH. The first stage of CAA involved leptomeningeal and neocortical vessels. The second stage was characterized by additional A beta deposition in allocortical and midbrain vessels. Finally, in a third stage, CAA was observed in the basal ganglia, the thalamus, and in the lower brainstem. In contrast, AS/LH initially affected the basal ganglia in stage A. In stage B this pathology made inroads into the deep white matter, the leptomeningeal arteries of the cortex, the cerebellum, and into the thalamus. Stage C was characterized by AS/LH in brainstem vessels. Our results demonstrate widespread CAA and AS/LH to be associated with the

  7. A Laboratory Phenotype/Genotype Correlation of 1167 French Patients From 670 Families With von Willebrand Disease

    PubMed Central

    Veyradier, Agnès; Boisseau, Pierre; Fressinaud, Edith; Caron, Claudine; Ternisien, Catherine; Giraud, Mathilde; Zawadzki, Christophe; Trossaert, Marc; Itzhar-Baïkian, Nathalie; Dreyfus, Marie; d’Oiron, Roseline; Borel-Derlon, Annie; Susen, Sophie; Bezieau, Stéphane; Denis, Cécile V.; Goudemand, Jenny

    2016-01-01

    Abstract von Willebrand disease (VWD) is a genetic bleeding disease due to a defect of von Willebrand factor (VWF), a glycoprotein crucial for platelet adhesion to the subendothelium after vascular injury. VWD include quantitative defects of VWF, either partial (type 1 with VWF levels <50 IU/dL) or virtually total (type 3 with undetectable VWF levels) and also qualitative defects of VWF (type 2 variants with discrepant antigenic and functional VWF levels). The most bleeding forms of VWD usually do not concern type 1 patients with the mildest VWF defects (VWF levels between 30 and 50 IU/dL). The French reference center for VWD performed a laboratory phenotypic and genotypic analysis in 1167 VWD patients (670 families) selected by their basic biologic phenotype: type 3, type 2, and type 1 with VWF levels <30 IU/dL. In these patients indeed, to achieve an accurate diagnosis of VWD type and subtype is crucial for the management (treatment and genetic counseling). A phenotype/genotype correlation was present in 99.3% of cases; 323 distinct VWF sequence variations (58% of novel) were identified (missense 67% versus truncating 33%). The distribution of VWD types was: 25% of type 1, 8% of type 3, 66% of type 2 (2A: 18%, 2B: 17%, 2M: 19%, 2N: 12%), and 1% of undetermined type. Type 1 VWD was related either to a defective synthesis/secretion or to an accelerated clearance of VWF. In type 3 VWD, bi-allelic mutations of VWF were found in almost all patients. In type 2A, the most frequent mechanism was a hyper-proteolysis of VWF. Type 2B showed 85% of patients with deleterious mutations (distinct from type 2B New York). Type 2M was linked to a defective binding of VWF to platelet glycoprotein Ib or to collagen. Type 2N VWD included almost half type 2N/3. This biologic study emphasizes the complex mechanisms for both quantitative and qualitative VWF defects in VWD. In addition, this study provides a new epidemiologic picture of the most bleeding forms of VWD in which

  8. Plasma zinc levels inversely correlate with vascular cell adhesion molecule-1 concentration in children with sickle cell disease.

    PubMed Central

    Kuvibidila, Solo R.; Sandoval, Manuel; Lao, Juan; Velez, Maria; Yu, Lolie; Ode, David; Gardner, Renée; Lane, Gerald; Warrier, Raj P.

    2006-01-01

    Zinc deficiency has been implicated in impaired cell-mediated immunity of children with sickle cell disease (SCD). However, its influence on the expression of vascular cell-adhesion molecule-1 (VCAM-1) on endothelial cells, a protein involved in vasoocclusion, has not been previously investigated. We therefore measured (soluble) sVCAM-1 and zinc in 76 SCD children and 96 non-SCD children, mean age 7.73 years and 11.24 years, respectively. Although mean zinc levels of both groups were within the normal range (approximately 14.5 micromol/l), 14.5 % of SCD and 11% of non-SCD children (without inflammation) had levels below normal (10.7 micromol/L). Mean sVCAM-1 concentrations of SCD children (837 microg/l) were significantly higher than those of controls (627 microg/l) (p < 0.001). Differences persisted after taking into account age, hemoglobin phenotype, and inflammation (alpha-l acid glycoprotein >l g/l and C-reactive protein >10 mg/I). sVCAM-1 negatively correlated with serum (r = -0.444) and red blood cells zinc (r = -0.242, p < 0.05) but not with acute-phase proteins. Mean sVCAM-1 tended to be higher in SCD children with than in those without a history of a health problem (infection, pain crisis or were transfused; not significant). Data suggest that zinc may modulate the clinical status of SCD children through VCAM-1 expression, and zinc supplementation may be beneficial in these patients. PMID:16916123

  9. The Cerebrospinal Fluid Neurogranin/BACE1 Ratio is a Potential Correlate of Cognitive Decline in Alzheimer’s Disease

    PubMed Central

    De Vos, Ann; Struyfs, Hanne; Jacobs, Dirk; Fransen, Erik; Klewansky, Tom; De Roeck, Ellen; Robberecht, Caroline; Van Broeckhoven, Christine; Duyckaerts, Charles; Engelborghs, Sebastiaan; Vanmechelen, Eugeen

    2016-01-01

    Background: In diagnosing Alzheimer’s disease (AD), ratios of cerebrospinal fluid (CSF) biomarkers, such as CSF Aβ1-42/tau, have an improved diagnostic performance compared to the single analytes, yet, still a limited value to predict cognitive decline. Since synaptic dysfunction/loss is closely linked to cognitive impairment, synaptic proteins are investigated as candidate CSF AD progression markers. Objective: We studied CSF levels of the postsynaptic protein neurogranin and protein BACE1, predominantly localized presynaptically, and their relation to CSF total-tau, Aβ1-42, Aβ1-40, and Aβ1-38. All six analytes were considered as single parameters as well as ratios. Methods: Every ELISA involved was based on monoclonal antibodies, including the BACE1 and neurogranin immunoassay. The latter specifically targets neurogranin C-terminally truncated at P75, a more abundant species of the protein in CSF. We studied patients with MCI due to AD (n = 38) and 50 dementia due to AD patients, as well as age-matched cognitively healthy elderly (n = 20). A significant subset of the patients was followed up by clinical and neuropsychologically (MMSE) examinations for at least one year. Results: The single analytes showed statistically significant differences between the clinical groups, but the ratios of analytes indeed had a higher diagnostic performance. Furthermore, only the ratio of CSF neurogranin trunc P75/BACE1 was significantly correlated with the yearly decline in MMSE scores in patients with MCI and dementia due to AD, pointing toward the prognostic value of the ratio. Conclusion: This is the first study demonstrating that the CSF neurogranin trunc P75/BACE1 ratio, reflecting postsynaptic/presynaptic integrity, is related to cognitive decline. PMID:27392859

  10. Serum IL-6 and IL-23 Levels and Their Correlation with Angiogenic Cytokines and Disease Activity in Ankylosing Spondylitis, Psoriatic Arthritis, and SAPHO Syndrome

    PubMed Central

    Przepiera-Będzak, Hanna; Fischer, Katarzyna; Brzosko, Marek

    2015-01-01

    Objectives. To assess serum interleukin-6 (IL-6) and interleukin-23 (IL-23) and their correlation with angiogenic cytokines and disease activity in ankylosing spondylitis (AS), psoriatic arthritis (PsA), and SAPHO syndrome. Patients and Methods. We studied 152 spondyloarthritis (SpA) patients: 69 PsA, 61 AS, 22 SAPHO, and 29 controls. We recorded age, sex, disease duration, and treatment. We assessed BASDAI, VAS, and PASI scores. Serum IL-6, IL-23, VEGF, EGF, FGFb, and FGFa levels were determined using ELISA. We estimated ESR and CRP. Results. Serum IL-6 and IL-23 levels were higher in SpA than in control (P < 0.00001 and P = 0.0004, resp.). There was a positive correlation between serum IL-6 and CRP in AS (P = 0.000001), PsA (P = 0.000001), and SAPHO (P = 0.0003) patients. There was a positive correlation between serum IL-6 and ESR in AS (P = 0.000001), PsA (P = 0.002), and SAPHO (P = 0.02) patients. There was no correlation of serum IL-6 and IL-23 with VAS, BASDAI, and angiogenic cytokines in SpA. Conclusions. Serum IL-6 but not serum IL-23 correlated with ESR and CRP in SpA. No correlation was found of serum IL-6 and IL-23 with VAS, BASDAI, and angiogenic cytokines. PMID:26339141

  11. State of the art in the diagnosis and management of interstitial lung disease.

    PubMed

    Buzan, Maria T A; Pop, Carmen Monica

    2015-01-01

    The interstitial lung diseases (ILDs) are a diverse group of disorders characterized by a varying combination of inflammation and fibrosis of the pulmonary parenchyma. Treatment and prognosis of ILD typically depend on the underlying ILD subtype, highlighting the importance of accurate classification and diagnosis. Besides a thorough history and clinical examination, the protocol should include a 6-minute walk test, chest radiography, high-resolution computed tomography, biochemical analysis, pulmonary function tests, blood gas analysis, bronchoalveolar lavage, and, when necessary, a lung biopsy. The final diagnosis of ILD entities requires dynamic interaction between clinicians, radiologists and pathologists to reach a clinico-radiologic-pathologic diagnosis, the gold standard no longer being the histology but rather a multidisciplinary approach.

  12. Aerobic capacity correlates to self-assessed physical function but not to overall disease activity or organ damage in women with systemic lupus erythematosus with low-to-moderate disease activity and organ damage.

    PubMed

    Boström, C; Dupré, B; Tengvar, P; Jansson, E; Opava, C H; Lundberg, I E

    2008-02-01

    The present aim is to investigate the relationships between aerobic capacity and disease activity, organ damage, health-related quality of life (HRQL) and physical activity in 34 women with systemic lupus erythematosus (SLE) with low-to-moderate disease activity and organ damage. Mean age was 51 (SD 10) years, disease duration 17 (SD 11) years. Aerobic capacity (maximal oxygen uptake/VO2 max) was measured with a bicycle ergometer exercise test. Overall disease activity was assessed with Systemic Lupus Activity Measure (SLAM) and the modified Systemic Lupus Erythematosus-Disease Activity Index (modified SLE-DAI), overall organ damage with the Systemic Lupus International Collaboration Clinics/American College of Rheumatology-Damage Index, [SLICC/(ACR)-DI], HRQL with the 36-item Short-form health-survey (SF-36) and physical activity with a self-assessed question. The women who were low-to-moderately physically active had 89-92% (P < or = 0.001) of VO2 max predicted for sedentary women. Maximal oxygen uptake (L/min, mL/min/kg) correlated to SF-36 physical function (rs = 0.49, rs = 0.72) (P < or = 0.01), but not (rs < or = 0.25) to other HRQL scales, overall disease activity or organ damage or physical activity. The correlation between aerobic capacity and physical function and the absence of correlation between aerobic capacity and physical activity, suggest a possible disease-related factor behind the low aerobic capacity. However, with no correlation between aerobic capacity and overall disease activity and organ damage, low physical activity may contribute to the low aerobic capacity in our sample.

  13. Correlations between skin lesions induced by anti-tumor necrosis factor-α and selected cytokines in Crohn's disease patients

    PubMed Central

    Włodarczyk, Marcin; Sobolewska, Aleksandra; Wójcik, Bartosz; Loga, Karolina; Fichna, Jakub; Wiśniewska-Jarosińska, Maria

    2014-01-01

    AIM: To investigate the correlation between the appearance of skin lesions and concentration of interleukin (IL)-17A, IL-23 and interferon-γ (IFN-γ) in Crohn’s disease (CD) patients during anti-tumor necrosis factor-α (TNF-α) therapy METHODS: A prospective study included 30 adult patients with CD of Caucasian origin (19 men and 11 women; mean age ± SD 32.0 ± 8.6 years) during biological therapy with anti-TNF-α antibodies from January 2012 to March 2013. Eighteen patients were treated with infliximab, seven with adalimumab and five with certolizumab. Inclusion criteria were exacerbation of the underlying disease, Crohn’s Disease Activity Index over 300 and the ineffectiveness of previously used non-biological therapies. Patients with a history of psoriasis, atopic dermatitis and other autoimmune skin lesions were excluded from the study. The control group consisted of 12 healthy subjects. A diagnostic survey was carried out, blood tests and careful skin examination were performed, and the serum levels of IL-17, IL-23 and IFN-γ were measured using an enzyme-linked immunosorbent assays technique. Dermatoses that have developed in the course of biological therapy in patients who had no pre-existing skin lesions of similar character were qualified as skin lesions induced by anti-TNF-α therapy. RESULTS: Skin manifestations occurred in 18 of CD patients during the anti-TNF-α therapy (60%), in the average time of 10.16 ± 3.42 mo following the beginning of the 52-wk treatment cycle. Skin lesions observed in CD patients during biological therapy included psoriasiform lesions (44.4%), and eczema forms lesions (22.2%). In CD patients with drug induced skin lesions significantly higher levels of hemoglobin (13.3 ± 1.5 g/dL vs 10.8 ± 1.9 g/dL, P = 0.018) and hematocrit (39.9% ± 4.5% vs 34.3% ± 5.4%, P = 0.01), as well as a significantly lower level of platelets (268 ± 62 × 103/μL vs 408 ± 239 × 103/μL, P = 0.046) was observed compared with CD patients

  14. Bovine coronavirus antibody titers at weaning negatively correlate with incidence of bovine respiratory disease in the feed yard

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine respiratory disease complex (BRDC) is a multifactorial disease caused by complex interactions among viral and bacterial pathogens, stressful management practices and host genetic variability. Although vaccines and antibiotic treatments are readily available to prevent and treat infection caus...

  15. Positive correlation between replication rate and pathotype of Marek’s disease virus strains in maternal antibody negative chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Marek’s disease (MD) is a highly contagious lymphoproliferative disease of chickens associated with large economic losses worldwide. The etiological agent, Marek’s disease virus (MDV), can be divided into three pathotypes: virulent (v), very virulent (vv), and very virulent plus (vv+). While previou...

  16. Correlation between the Modified Systemic Lupus Erythematosus Disease Activity Index 2000 and the European Consensus Lupus Activity Measurement in juvenile systemic lupus erythematosus.

    PubMed

    Sato, J O; Corrente, J E; Saad-Magalhães, C

    2016-11-01

    Objective The objective of this study was to assess Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and European Consensus Lupus Activity Measurement (ECLAM) disease activity correlation in addition to their respective correlation to Pediatric Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (Ped-SDI), in juvenile systemic lupus erythematosus (JSLE). Methods The activity indices were scored retrospectively and summarized by adjusted means during follow-up. The Ped-SDI was scored during the last visit for those with more than six months follow-up. Pearson correlation between the Modified SLEDAI-2K and ECLAM, as well as Spearman correlations between the Modified SLEDAI-2K, ECLAM, and Ped-SDI were calculated. The receiver operating characteristic (ROC) curve was calculated for both activity indices discriminating damage measured by Ped-SDI. Results Thirty-seven patients with mean age at diagnosis 11 ± 2.9 years and mean follow-up time 3.2 ± 2.4 years were studied. The Modified SLEDAI-2K and ECLAM adjusted means were highly correlated ( r = 0.78, p < 0.001). Similarly, Spearman correlation between the activity indices was also high ( rs > 0.7, p < 0.001), but Modified SLEDAI-2K and ECLAM correlation with Ped-SDI was only moderate. ROC analysis discriminant performance for both activity indices resulted in area under curve (AUC) of 0.74 and 0.73 for Modified SLEDAI-2K and ECLAM, respectively. Conclusion The high correlation found between the Modified SLEDAI-2K and ECLAM adjusted means indicated that both tools can be equally useful for longitudinal estimates of JSLE activity.

  17. The role of interleukin 17-mediated immune response in Chagas disease: High level is correlated with better left ventricular function

    PubMed Central

    Gomes, Juliana A. S.; Damasio, Marcos Paulo S.; Nunes, Maria Carmo P.; Costa, Henrique S.; Medeiros, Nayara I.; Fares, Rafaelle C. G.; Chaves, Ana Thereza; Corrêa-Oliveira, Rodrigo; Rocha, Manoel Otávio C.

    2017-01-01

    Interleukin 17A (IL-17A) has been associated with protective rather than pathogenic response in Chagas disease (ChD). However, it is not established whether or not IL-17A-mediated immune response is correlated with patient’s left ventricular (LV) function in ChD. To address this question we have gathered cardiac functional parameters from ChD patients and analysed the possible relationship between their plasma IL-17A levels and LV function. Plasma IL-17A levels were measured by BD Cytometric Bead Array (CBA) in 240 patients with positive specific serology for Trypanosoma cruzi (T. cruzi) grouped as indeterminate (IND) and Chagas cardiomyopathy (CARD) forms. The levels of IL-17A in ChD patients were compared with 32 healthy individuals, mean age of 39 years, 50% male, that were also included as a control group (non-infected [NI]). The overall mean age of ChD patients was 46 years and 52% were male. The IND group included 95 asymptomatic patients, with ages ranging from 27 to 69 years (mean of 43 years), and 42.1% of them were male. The CARD group included 145 patients, which 58.6% were male, with ages ranging from 23 to 67 years (mean of 49). The IND group presented substantially higher levels of IL-17A, median of 26.16 (3.66–48.33) as compared to both the CARD group, median of 13.89 (3.87–34.54) (P <0.0001), and the NI group, median of 10.78 (6.23–22.26) (P <0.0001). The data analysis demonstrated that the IND group comprises a significantly greater proportion (P <0.001) of high IL-17A producers (52.6%, 50 of 95 subjects) than do the other groups. A significant direct correlation was verified between IL-17A levels and cardiac function expressed by LV ejection fraction (LVEF), LV diastolic diameter (LVDd), and body surface area (BSA)-indexed LVDd as well as ratio of the early diastolic transmitral flow velocity to early diastolic mitral annular velocity (E/e’) in both groups. We demonstrated that plasma IL-17A levels has an accurate sensitivity and

  18. Correlation between glomerular filtration rate and urinary N acetyl-beta-D glucosaminidase in children with persistent proteinuria in chronic glomerular disease

    PubMed Central

    Hong, Jeong Deok

    2012-01-01

    Purpose Urinary excretion of N acetyl-beta-D glucosaminidase (NAG) and β2-microglobulin (β2-M) was increased in the presence of proximal tubular damage. Based on these urinary materials, we investigated the ability of expecting renal function in chronic glomerular diseases. In this study, we evaluated the relationship between glomerular filtration rate (GFR) urinary NAG, and urinary β2-M. Methods We evaluated 52 children with chronic kidney disease at the Chung-Ang University Hospital between January 2003 and August 2009. We investigated the 24-hour urinalysis and hematologic values in all 52 patients. Serum creatinine, creatinine clearance (Ccr), serum cystatin C, urinary β2-M and urinary NAG were measured. Results Out of 52 patients, there were 13 children with minimal change in disease, 3 children with focal segmental glomerulosclerosis, 17 children with immunoglobulin A nephropathy, 15 children with Henoch-Schönlein purpua nephritis, 3 children with poststreptococcal glomerulonephritis, and 1 child with thin glomerular basement membrane disease. In these patients, there were significant correlation between the Ccr and urinary NAG (r=-0.817; P<0.01), and between the GFR (as determined by Schwartz method) and urinary NAG (r=-0.821; P<0.01). In addition, there was a significant correlation between the GFR (as determined by Bokencamp method) and urinary NAG (r=-0.858; P<0.01). Conclusion In our study, there was a significant correlation between the GFR and urinary NAG, but there was no correlation between the GFR and urinary β2-M, suggesting that the GFR can be predicted by urinary NAG in patients with chronic glomerular disease. PMID:22574074

  19. Antibodies against Apoptotic Cells Present in End-stage Lung Disease Patients Do Not Correlate with Clinical Outcome after Lung Transplantation

    PubMed Central

    Budding, Kevin; van de Graaf, Eduard A.; Kardol-Hoefnagel, Tineke; Oudijk, Erik-Jan D.; Kwakkel-van Erp, Johanna M.; Hack, C. Erik; Otten, Henny G.

    2017-01-01

    Antibodies against HLA and non-HLA are associated with transplantation outcome. Recently, pretransplant serum IgG antibody levels against apoptotic cells were found to correlate with kidney allograft loss. We investigated the presence of these antibodies in lung transplantation (LTx) patients and evaluated the correlation of pre-LTx serum levels of IgG antibodies against apoptotic cells with LTx outcome. These cells included donor lung endothelial cells (ECs) obtained from lung perfusion fluid collected during LTx procedure. Cells were isolated, expanded in vitro, and analyzed as targets for antiapoptotic cell reactivity. Cultured cells exhibited EC morphology and were CD31+, CD13+, and vWF+. End-stage lung disease patients showed elevated serum IgG levels against apoptotic lung EC (p = 0.0018) compared to healthy controls. Interestingly, the levels of circulating antibodies directed against either apoptotic Jurkat cells or apoptotic lung ECs did not correlate, suggesting a target cell specificity. We observed no correlation between chronic or acute rejection and pre-LTx serum levels of antiapoptotic antibodies. Also, these levels did not differ between matched patients developing chronic rejection or not during follow-up or at the time of diagnosis, as they remained as high as prior to transplantation. Thus, circulating levels of antiapoptotic cell antibodies are elevated in end-stage lung disease patients, but our data do not correlate with outcome after LTx. PMID:28377770

  20. Elevated Expression of Immunoreceptor Tyrosine-Based Inhibitory Motif (TIGIT) on T Lymphocytes is Correlated with Disease Activity in Rheumatoid Arthritis

    PubMed Central

    Luo, Qing; Deng, Zhen; Xu, Chuxin; Zeng, Lulu; Ye, Jianqing; Li, Xue; Guo, Yang; Huang, Zikun; Li, Junming

    2017-01-01

    Background It is well known that lymphocytes play an important role in rheumatoid arthritis (RA). T cell immunoreceptors with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (TIGIT) have immunosuppressive co-stimulatory molecules that mediate inhibitory effects, but their roles in RA are poorly understood. Material/Methods Were recruited 76 patients with RA and 33 healthy controls (HC). Clinical manifestations, laboratory measurements, physical examination, and medical history of RA patients were recorded. The expression of TIGIT on CD3+ T lymphocytes, B lymphocytes, monocytes, neutrophils, CD3+CD4+ T lymphocytes, and CD3+CD8+ T lymphocytes was determined using flow cytometry. The expression of TIGIT on T lymphocytes in patients with RA was further analyzed to investigate its correlations with markers of autoimmune response, inflammation, and disease activity in RA. Results Compared with HC, the expression levels of TIGIT on CD3+CD4+ T lymphocytes and CD3+CD8+ T lymphocytes were significantly increased in patients with RA (P < 0.01). The frequency of TIGIT-expressing CD3+CD4+ T lymphocytes was positively correlated with RF, increased ACPA, ESR, and CRP levels. The frequency of TIGIT-expressing CD3+CD8+ T lymphocytes was positively correlated with RF and ESR levels. Furthermore, the expression level of TIGIT on CD3+CD4+ T lymphocytes was positively correlated with the DAS28 score in RA. Conclusions The expression levels of TIGIT on T lymphocytes were elevated and correlated with disease activity in RA. PMID:28282368

  1. Correlations between mean echogenicity and material properties of normal and diseased equine superficial digital flexor tendons: an in vitro segmental approach.

    PubMed

    Crevier-Denoix, N; Ruel, Y; Dardillat, C; Jerbi, H; Sanaa, M; Collobert-Laugier, C; Ribot, X; Denoix, J-M; Pourcelot, P

    2005-11-01

    The objective of this study was to test the hypothesis that tendon echogenicity is associated with the material properties of the corresponding tendon site, especially in case of lesions, due to local changes in tendon matrix composition. Four normal and nine spontaneously injured equine superficial digital flexor tendons (SDFT) were isolated then ultrasonographically examined under tension, in a special device placed in a water bath. Ultrasonographic transversal images (7.5MHz linear transducer) of five segments along each tendon were digitized, and analyzed in order to measure the mean cross-sectional area (MCSA) and mean echogenicity (ME) of each segment. The tendons were then tested in traction until rupture in a testing machine. For each segment, stress and strain were determined throughout the test, and the elastic modulus (EM) was evaluated. The tendon lesions were also documented by histology. No correlation was found between ME and the material properties of normal tendon segments. At the rupture sites of the nine diseased tendons, ME was positively correlated with maximal stress and EM, whereas no correlation was demonstrated with maximal strain. Besides, a positive correlation was demonstrated between ME and both MCSA and EM, when the three metacarpal segments of the diseased tendons were considered. Although ME gives only rough information about tendon matrix structure, it does show, under these in vitro conditions, significant correlations with material properties of pathological tendon segments, which may improve the functional significance and therefore the prognostic value of the ultrasonographic examination of tendon lesions.

  2. Mapping correlations between ventricular expansion and CSF amyloid and tau biomarkers in 240 subjects with Alzheimer’s disease, mild cognitive impairment and elderly controls

    PubMed Central

    Chou, Yi-Yu; Leporé, Natasha; Avedissian, Christina; Madsen, Sarah K.; Parikshak, Neelroop; Hua, Xue; Shaw, Leslie M.; Trojanowski, John Q.; Weiner, Michael W.; Toga, Arthur W.; Thompson, Paul M.

    2009-01-01

    Automated ventricular mapping with multi-atlas fluid image alignment reveals genetic effects in Alzheimer’s disease, NeuroImage 40(2): 615–630); with this method, we calculated minimal numbers of subjects needed to detect correlations between clinical scores and ventricular maps. We also assessed correlations between emerging CSF biomarkers of Alzheimer’s disease pathology and localizable deficits in the brain, in 80 AD, 80 mild cognitive impairment (MCI), and 80 healthy controls from the Alzheimer’s Disease Neuroimaging Initiative. Six expertly segmented images and their embedded parametric mesh surfaces were fluidly registered to each brain; segmentations were averaged within subjects to reduce errors. Surface-based statistical maps revealed powerful correlations between surface morphology and 4 variables: (1) diagnosis, (2) depression severity, (3) cognitive function at baseline, and (4) future cognitive decline over the following year. Cognitive function was assessed using the mini-mental state exam (MMSE), global and sum-of-boxes clinical dementia rating (CDR) scores, at baseline and 1-year follow-up. Lower CSF Aβ1–42 protein levels, a biomarker of AD pathology assessed in 138 of the 240 subjects, were correlated with lateral ventricular expansion. Using false discovery rate (FDR) methods, 40 and 120 subjects, respectively, were needed to discriminate AD and MCI from normal groups. 120 subjects were required to detect correlations between ventricular enlargement and MMSE, global CDR, sum-of-boxes CDR and clinical depression scores. Ventricular expansion maps correlate with pathological and cognitive measures in AD, and may be useful in future imaging-based clinical trials. PMID:19236926

  3. Natriuretic Peptide and High-Sensitive Troponin T Concentrations Correlate with Effectiveness of Short-Term CPAP in Patients with Obstructive Sleep Apnea and Coronary Artery Disease

    PubMed Central

    Strehmel, Ralf; Valo, Misa; Teupe, Claudius

    2016-01-01

    The risk of cardiovascular complications is increased in patients with obstructive sleep apnea (OSA). Continuous positive airway pressure (CPAP) is the most effective way to treat clinically significant OSA. We hypothesized that the concentrations of the cardiac risk markers N-terminal brain natriuretic peptide (NT-proBNP) and high-sensitive troponin T (hs-TropT) correlate with the effectiveness of CPAP therapy in patients with OSA and coexisting coronary artery disease (CAD). Twenty-one patients with severe OSA and coexisting CAD (group 1) and 20 control patients with severe OSA alone (group 2) were treated with CPAP and monitored by laboratory-based polysomnography. NT-proBNP and hs-TropT levels were measured before and after CPAP. Apnea–hypopnea index (AHI) and oxygen desaturation were similar in both groups. In group 1, hs-TropT levels correlated with AHI and oxygen desaturation upon CPAP. Elevated NT-proBNP levels in group 1 were significantly reduced by CPAP. NT-proBNP levels correlated with AHI and showed negative correlation with ST-segment depression. No such correlations were found in group 2. CPAP has the potential to normalize elevated NT-proBNP serum levels in patients with severe OSA and coexisting CAD. Levels of NT-proBNP and hs-TropT correlated with AHI and oxygen desaturation. PMID:27980444

  4. Correlation of serum toll like receptor 9 and trace elements with lipid peroxidation in the patients of breast diseases.

    PubMed

    Karki, Kanchan; Pande, Deepti; Negi, Reena; Khanna, Seema; Khanna, Ranjana S; Khanna, Hari D

    2015-04-01

    Toll-like receptors are recognized as redox sensitive receptor proteins and have been implicated in cellular response to oxidative stress. Altered pro-oxidant-antioxidant balance leads to an increased oxidative damage and consequently play an important role in breast diseases. The study was designed to access the oxidative stress status by quantification of byproducts generated during lipid peroxidation and inadequate trace elements during oxidative damage and its effects on the toll like receptor (TLR) activity in patients of breast diseases. Decreased levels of selenium, copper, zinc, magnesium and iron with elevated levels of malondialdehyde (marker of lipid peroxidation) were accompanied by decreased TLR activity in patients of benign breast diseases as well as breast carcinoma. A similar pattern was observed with the advancement of disease and its subsequent progression in breast carcinoma patients. Results of multinomial regression analysis suggest benign breast disease patients are at higher risk of developing breast cancer with high odds ratio of lipid damage.

  5. Serum levels of interleukin 6 in recently hospitalized tick-borne encephalitis patients correlate with age, but not with disease outcome

    PubMed Central

    Toporkova, M G; Aleshin, S E; Ozherelkov, S V; Nadezhdina, M V; Stephenson, J R; Timofeev, A V

    2008-01-01

    Infection with many encephalitic viruses is associated with the induction of the proinflammatory cytokine interleukin (IL)-6. In some situations, induction of high levels of this cytokine is associated with a protective response, but in others it can be linked to tissue damage and disease. In the studies reported here, levels of serum IL-6 and virus-specific antibodies were measured on admission to hospital and correlated with clinical outcomes. Only some patients demonstrated raised levels of serum IL-6, and there was no correlation between high levels of this cytokine and either gender or the severity of clinical disease. A statistically significant association between raised IL-6 and age was observed, with all individuals below the age of 26 showing normal levels of serum IL-6, regardless of clinical presentation. Furthermore, not all patients had detectable levels of virus-specific serum immunoglobulin G (IgG) antibodies, but an inverse and statistically significant correlation between raised IL-6 levels and IgG titre was observed. Consequently, serum levels of IL-6 cannot be used as a reliable indicator of disease outcome. PMID:18462209

  6. Condom use and correlates of African American adolescent females' infrequent communication with sex partners about preventing sexually transmitted diseases and pregnancy.

    PubMed

    Crosby, Richard A; DiClemente, Ralph J; Wingood, Gina M; Cobb, Brenda K; Harrington, Kathy; Davies, Susan L; Hook, Edward W; Oh, M Kim

    2002-04-01

    This study of 522 African American female adolescents, ages 14 to 18, investigated associations between condom use and infrequently communicating with sex partners about sexually transmitted diseases (STDs) and pregnancy prevention. Correlates of infrequent communication were identified. Sexually active adolescents were recruited from schools and adolescent medicine clinics in low-income neighborhoods of Birmingham, Alabama. Adolescents completed a self-administered survey and face-to-face interview. Communication frequency was assessed using a five-item scale. Infrequent communication was significantly associated with lower odds of condom use. Multivariate correlates of infrequent communication were less frequent communication with parents about STD/pregnancy prevention, recent sex with a nonsteady partner, low perceived ability to negotiate condom use and fear of this negotiation, and low motivation to use condoms. Given the importance of partner communication in promoting safer sex behaviors, STD and pregnancy prevention programs may benefit adolescents by addressing the identified psychosocial correlates of infrequent communication with their partners.

  7. Comparison of two screening tests in Alzheimer's disease. The correlation and reliability of the Mini-Mental State Examination and the modified Blessed test.

    PubMed

    Fillenbaum, G G; Heyman, A; Wilkinson, W E; Haynes, C S

    1987-09-01

    The Mini-Mental State Examination (MMSE) and the Blessed Orientation-Memory-Concentration test (BOMC), a six-item derivative of the Blessed Information-Memory-Concentration Test, were each administered to 36 patients with a clinical diagnosis of Alzheimer's disease. In 24 patients, both tests were readministered a month later. The correlation between the MMSE and BOMC was -0.83 with a test-retest correlation of 0.89 (MMSE) and 0.77 (BOMC). Factor analysis indicated that the multiple MMSE cognitive components could be explained by two factors, which together accounted for 66% of the variance. These factors are conceptually similar to the components of the BOMC, and so may explain the substantial correlation between the two tests. Since these cognitive status tests seem to be equivalent for Alzheimer patients, the briefer measure (BOMC), which offers additional advantages, may be preferred.

  8. Assessment and Correlation of Urea and Creatinine Levels in Saliva and Serum of Patients with Chronic Kidney Disease, Diabetes and Hypertension– A Research Study

    PubMed Central

    Nagrajappa, Anil Kumar; Ravi, K.S

    2016-01-01

    Introduction Serum urea and creatinine are most widely accepted parameters to assess Chronic Kidney Disease (CKD)status as well as to assess renal status in susceptible diabetic and hypertensive subjects. Aim To assess and correlate the serum and salivary urea and creatinine levels of CKD, diabetes mellitus and hypertensive subjects. Materials and Methods This cross-sectional study was done on 120 subjects involving 30 CKD, 30 diabetic, 30 hypertensive subjects and 30 healthy controls. After collection of saliva and blood samples, urea was analyzed by enzymatic ca