CIC Edizioni Internazionali. Liver cirrhosis in patients newly diagnosed with neurological phenotype of Wilson s disease
|
|
- Rachel Lester
- 5 years ago
- Views:
Transcription
1 Liver cirrhosis in ptients newly dignosed with neurologicl phenotype of Wilson s disese Adm Przybyłkowski, MD, PhD Grżyn Gromdzk MD, PhD,b Grzegorz Chbik, MD b Agt Wierzchowsk, MD b Tomsz Litwin, MD, PhD b Ann Członkowsk, MD, PhD,b Deprtment of Experimentl nd Clinicl Phrmcology, Medicl University of Wrsw, Wrsw, Polnd b Second Deprtment of Neurology, Institute of Psychitry nd Neurology, Wrsw, Polnd Correspondence to: Adm Przybyłkowski E-mil: przybylkowski@wum.edu.pl Summry Wilson's disese (WD) cn mnifest itself in different clinicl forms, the neurologicl nd heptic ones being the most common. It is suggested tht neurologicl signs nd psychitric symptoms develop secondry to liver involvement. The im of this study ws to chrcterize the liver disese in ptients newly dignosed with the neurologicl form of WD. Tretment-nive ptients dignosed with WD were clssified into three phenotypic groups: heptic, neurologicl nd pre-symptomtic. Liver involvement ws scertined through surrogte mrkers: bdominl ultrsound nd lbortory prmeters. In ddition, study prticipnts were screened for esophgel vrices. Of 53 consecutively dignosed WD ptients, 23 individuls (43.4%) hd predominntly neurologicl presenttion. In this group, cirrhosis ws dignosed in 11 (47.8%) subjects. Esophgel vrices were present in ll of them. In every ptient with neurologicl WD, there ws t lest one sign of heptic disese on ultrsound exmintion, indicting universl presence of liver involvement. The prevlence of surrogte signs of cirrhosis ws similr in ptients with the neurologicl nd in those with the heptic phenotype. KEY WORDS: esophgel vrices, liver cirrhosis, Wilson s disese Introduction Wilson s disese (WD) is n utosoml recessive inborn error of metbolism which results in defective copper homeostsis nd systemic copper toxicosis. The metbolic defect is due to impired copper trnsport resulting from muttions in the ATP7B gene encoding P-type denosine triphosphtse (Tnzi et l., 1993). ATP7B is involved in excretion of copper from heptocytes into the bile. The billelic ATP7B muttion in WD ptients is responsible for copper ccumultion within the liver nd other orgns. This copper overlod leds to orgn dmge nd the clinicl mnifesttions of WD (Al et l., 2007). Three brod ctegories re recognized on the bsis of the signs nd symptoms: heptic, neurologicl nd pre-symptomtic (symtopmtic). Furthermore, there is wide clinicl spectrum even within ech of these phenotypic ctegories. For exmple, liver disese in ptients clssified s heptic WD rnges from symptomtic elevtion of liver enzymes to cute heptitis, occult cirrhosis nd fulminnt heptic filure. Similrly, neurogicl WD ptients show wide clinicl spectrum of neurologicl mnifesttions, which rnge from behviorl symptoms to incpcitting movement disorder (Al et l., 2007). The nturl history of WD is still not fully understood. It is not cler whether neurologicl signs nd symptoms occur erly in the course of the disese when liver involvement is mild (i.e., pre-cirrhotic) or whether they pper fter the development of liver dmge nd cirrhosis. It hs been suggested tht neuropsychitric symptoms in WD develop secondry to liver involvement (Hrris et l., 2007). However, there is pucity of informtion on the true prevlence nd stging of liver disese mong ptients with neurologicl symptomtology. Correct stging of liver disese, especilly the detection of dvnced liver fibrosis or cirrhosis in ptients with WD, is of therpeutic nd prognostic importnce. For exmple, the presence of cirrhosis lters the mngement of ptients s regrds monitoring for esophgel nd gstric vrices nd heptocellulr crcinom (D'Amico nd Luc, 1997; Schuppn nd Afdhl, 2008; Wlshe et l., 2003). Histologicl exmintion of percutneous biopsy specimens is the gold stndrd for ssessment of fibrosis nd cirrhosis; however, liver biopsy is n invsive procedure. Serum mrkers nd ultrsonogrphic chrcteristics of liver prenchym my be used s surrogte mrkers of cirrhosis (Schuppn nd Afdhl, 2008). Ultrsonogrphy (USG) is non-invsive nd inexpensive procedure for the dignosis of prenchyml diseses of the liver. The sensitivity nd specificity of USG in the detection of cirrhosis vry between uthors, showing tht this method Functionl Neurology 2014; 29(1):
2 A. Przybylkowski et l. is highly dependent on the exminer s experience. Nevertheless it is believed tht USG cn show liver cirrhosis with cceptble dignostic ccurcy (Aube et l., 2004). In this prospective study, we imed to determine the extent of liver disese through surrogte lbortory mrkers nd bdominl ultrsound in consecutive series of newly dignosed WD ptients with the neurologicl phenotype, compring the findings with those recorded in ptients showing predominntly heptic presenttion. In ddition, we present the results of endoscopic screening for portl hypertension signs. Mterils nd methods Ptients A consecutive series of 53 dult ptients dignosed with WD t the Second Deprtment of Neurology, Institute of Psychitry nd Neurology, Wrsw, Polnd, nd t the Deprtment of Gstroenterology, Sint Ann s Hospitl, Wrsw, Polnd, were included in this study. Blood smples were obtined on dmission to hospitl. USG nd endoscopy were performed during initil evlution for WD. The study ws pproved by the locl ethics committee nd informed consent ws obtined from ll the ptients. The study protocol conforms to the ethicl guidelines of the 1975 Declrtion of Helsinki s reflected in priori pprovl by the institution's humn reserch committee. All ptients met the WD dignostic criteri of the 8 th Interntionl Meeting on Wilson disese nd Menkes disese (Ferenci et l., 2003). No ptient enrolled in the study hd received ny tretment for WD. The extent of the disese ws scertined on the bsis of the presence of heptic, neurologicl or psychitric signs nd symptoms. The comprehensive evlution llowed the ptients to be clssified into three phenotypic ctegories ccording to criteri proposed by Ferenci et l. (2003): - ptients with symptomtic liver disese without neurologicl nd psychitric symptoms were clssified s hving heptic presenttion; - ptients in whom neurologicl nd/or psychitric symptoms were present t dignosis were clssified s neurologicl WD; - ptients without heptic nd neuropsychitric symptoms (siblings of ffected WD ptients dignosed through fmily screening) were clssified s presymptomtic WD. Liver function tests nd non-invsive mrkers of liver fibrosis/cirrhosis For the ssessment of liver involvement, bttery of blood tests ws performed in ll the ptients. Detoxifiction nd excretory functions of the liver were ssessed determining the ctivity of: lnine minotrnsferse (ALT), sprgine minotrnsferse (AST) nd gmm-glutmyl trnspeptidse (GGTP). In ddition, bilirubin concentrtion ws mesured. Biosynthetic function of the liver ws scertined by mesuring serum lbumin concentrtion nd interntionl normlized rtio (INR). Thrombocytopeni resulting from sequestrtion of pltelets in congested spleen is frequently present in ptients with chronic liver disese; therefore, pltelet count ws mesured in ll the ptients. All tests were performed using stndrd lbortory methods. The following non-invsive mrkers of liver fibrosis were clculted: i) AST/ALT rtio (AAR); ii) AST to pltelet rtio index (APRI). The APRI is routine biochemicl nd hemtologicl test creted by Wi et l. (2003) to evlute the presence of liver cirrhosis. An AAR cutoff vlue of 1.0 ws set for predicting dvnced fibrosis (Mnning nd Afdhl, 2008), while the APRI threshold vlue for severe fibrosis ws set t 1.0. Abdominl ultrsound exmintion Ultrsound exmintion of the liver ws performed ccording to uniform protocol using Philips HD11XE (Philips Helthcre, Best, The Netherlnds), equipped with 2-5 MHz brodbnd curved rry trnsducer. The following seven vribles for dvnced liver fibrosis/cirrhosis were ssessed: nodulr liver surfce, inhomogeneity of liver prenchym, presence of collterl circultion, splenomegly, scites, portl vein dimeter nd men velocity of the flow in the portl vein (Aube et l., 1999). The surfce nodulrity vrible ws considered positive if, insted of stright nd regulr hyperechoic line, the liver surfce ppered s dotted or irregulr line. If the liver prenchym ws not homogeneous but showed res with different echogenicity, prenchyml inhomogeneity ws deemed to be present. Collterl circultion ws defined s umbilicl vein dimeter >3 mm or left gstric vein >5 mm or ny bnorml vein such s spleno-renl shunt. Spleen size ws ssessed by the longitudinl section nd the spleen ws considered enlrged when this ws >13 cm (Frnk et l., 1986). Ascites ws recorded when present. Portl vein dimeter ws considered bnorml when it ws >13 mm (Goyl et l., 2009). For portl vein ssessment, men flow velocity cut-off vlue of 15 cm/s ws used (Goyl et l., 2009). For the dignosis of cirrhosis, the following ultrsonogrphic criteri were rbitrrily estblished: presence of nodulr surfce ccompnied by t lest two other signs of liver fibrosis. Endoscopy Upper gstrointestinl trct endoscopy ws performed by two experienced endoscopists. The ptients were screened for the presence of esophgel vrices, portl-hypertensive gstropthy nd gstric vrices. Esophgel vrix stge ws defined ccording to the Itlin Liver Cirrhosis Project (ILCP) criteri (Merkel et l., 2000). ILCP group stging of vricel size is function of the percentge of the esophgel lumen occupied by the lrgest vrix: grde 1 vrix occupies <25% of the esophgel lumen, grde 2 vrix occupies 25-50% of the esophgel lumen, nd grde 3 vrix occupies > 50% of the esophgel lumen. 24 Functionl Neurology 2014; 29(1): 23-29
3 Liver involvement in neurologicl form of Wilson s disese Sttisticl nlysis The dt were nlyzed using STATISTICA 10.0 (SttSoft, Crcow, Polnd). The normlity of nlyzed vribles ws determined using the Kolmogorov- Smirnov nd Lilliefors tests. Normlly distributed vribles were presented s men nd stndrd devition. Vribles tht were not normlly distributed in the nlyzed popultion were presented s medin nd interqurtile rnge. Student s t-test nd the Mnn- Whitney U test were used for further nlysis of normlly/not-normlly distributed vribles, respectively. Ctegoricl vribles were compred between groups by Fisher s exct test. Reltionships between vribles were exmined using the Spermn rnk correltion coefficient. The significnce level ws set t Results Ptient chrcteristics Fifty-three consecutively dignosed ptients were phenotyped s heptic or neurologicl WD. The bseline chrcteristics of the ptients re presented in tble I. The symptoms nd signs suggestive of WD were neuropsychitric in 23 cses (43.4%) nd heptic in 19 cses (35.8%); the other 11 individuls were evluted for WD fter dignosis of the disese in sibling (20.7%). The study group comprised 25 (47.2%) women nd 28 (52.8%) men (Tble I). The men ge t dignosis of WD ws significntly lter in the neurologicl phenotype group compred with the heptic group: 35.3 yers (rnge 18-50) vs 26.3 yers (rnge 18-57; p<0.02). The men ge t dignosis of symptomtic ptients dignosed through fmily screening ws 27.8 yers (rnge 20-44). The men symptom durtion before dignosis did not differ between the groups. On physicl exmintion, heptic signs were present in 43.5% of the neurologicl group ptients, with peripherl edem being the most common sign (Tble I). Jundice ws present in three neurologicl ptients, while one subject presented fulminnt liver filure (Tble I). Tremor ws the most frequent neurologicl bnormlity, while 11 ptients complined of psychitric symptoms. Kyser-Fleischer (KF) ring ws detected in ll 23 ptients in the neurologicl group compred with 11 ptients in the heptic phenotype group (57.9%; p<0.0003). Four pre-symptomtic indi- Tble I - Bseline nd clinicl chrcteristics of the Wilson s disese ptients prticipting in the study. (n = 23) (n = 19) (n = 11) Age t dignosis (yers), men ± SD 35.3 ± ± ±8.0 Sex, n (%) - femle 10 (43.5) 8 (42.1) 7 (63.6) - mle 13 (56.5) 11 (57.9) 4 (36.4) Durtion of symptoms in yers, 1.0 (2.0) 1.0 (1.0) 0 medin (IQR) Heptic signs, n (%): 10 (43.5) 19 (100.0) - - heptomegly, n (%) 6 (26.1) 8 (42.1) - - jundice, n (%) 3 (13.0) 4 (21.1) - - scites, n (%) 2 (8.7) 3 (15.8) - - peripherl edem, n (%) 9 (39.1) 10 (52.6) - Neurologicl signs: - tremor, n (%) 15 (65.2) rigidity, n (%) 5 (21.7) dystoni, n (%) 5 (21.7) txi, n (%) 5 (21.7) - - Psychitric symptoms, n (%) 11 (47.8) - - Kyser-Fleischer ring; n (%) 23 (100.0) 11 (57.9) 4 (36.4) Serum ceruloplsmin in mg/dl 15.1 (28.5) 16.7 (37.5) 17.9 (24.4) (norml: 25-45); medin (IQR) Serum copper in µg/dl 42.7 (39.2) 46.0 (38.9) 63.9 (28.9) (norml: ); medin (IQR) Copper excretion in urine within 24 h in (297.0) (141.0) 83.0 (306.0) µg/24 h (norml: 0-50); medin (IQR) Abbrevitions: SD=stndrd devition; IQR=interqurtile rnge. p<0.05 for the comprison with the heptic group. Student s t-test or Mnn-Whitney U test for normlly/not normlly distributed vribles, respectively. Ctegoricl vribles were compred between groups by Fisher s exct test. Functionl Neurology 2014; 29(1):
4 A. Przybylkowski et l. viduls (16.4%) dignosed through fmily screening lso hd KF rings, finding tht underscores the insidiously progressive nture of WD. Tble II shows the results of muttion nlysis of the ATP7B gene. The H1069Q muttion ws the most common. Non-invsive mrkers of liver fibrosis/cirrhosis A significntly lower prevlence of bnorml liver function tests ws found mong the ptients exhibiting the neurologicl phenotype compred with the heptic phenotype; ALT nd AST were elevted in 30.4% of the neurologicl WD ptients compred with 63.2% of the heptic ptients (p<0.03); GGTP ws elevted in 17.4% vs 73.7%, respectively (p<0.0003). Moreover, the groups differed in bsolute vlues of lbortory tests (Tble III). Serum bilirubin, lbumin, INR nd pltelet count vlues did not differ significntly between the heptic phenotype group nd the neurologicl group. An AAR>1, positive for fibrosis, ws found in 16 (69.6%) neurologicl WD ptients nd in 10 (52.6%) ptients with the heptic phenotype. Six symptomtic subjects were lso positive for AAR. APRI>1 ws present in eight (34.8%) neurologicl ptients nd nine (47.4%) heptic ptients, but none from the fmily screening group. Abdominl ultrsound exmintion Irregulr liver surfce nd prenchyml inhomogeneity were present more frequently in the neurologicl WD ptients thn in the heptic WD ptients (Tble IV). Irregulr surfce ws not observed in ny ptient from the fmily screening group, but prenchyml inhomogeneity ws observed in three (27.3%) of them. Collterl circultion indicting underlying portl hypertension ws present in minority of WD ptients Tble II - Distribution of muttions of the ATP7B gene. (two ptients with the neurologicl nd two with the heptic phenotype). Splenomegly ws detected in seven (30.4%) neurologicl WD ptients nd in seven (36.8%) heptic WD ptients. Interestingly, sple - nomegly ws present in one symptomtic ptient dignosed through fmily screening. Free fluid in the peritonel cvity ws present in three (13.0%) neurologicl WD ptients compred with five (26.3%) ptients exhibiting the heptic phenotype. The frequency of portl vein dilttion nd the prevlence of decresed portl flow were similr in ptients with neurologicl nd heptic presenttion, but these signs were rre in siblings nd reltives of index cses. Ultrsonogrphic criteri for liver cirrhosis were fulfilled by 11 (47.8%) neurologicl ptients nd by seven (36.8%) heptic ptients. One ptient dignosed symptomticlly through fmily screening lso exhibited ultrsonogrphic signs of dvnced liver disese. In every ptient with neurologicl WD, there ws t lest one ultrsonogrphic sign, indicting universl presence of liver involvement. The number of ultrsonogrphic signs correlted significntly with APRI (ρ=0.5; p<0.05) nd with presence of esophgel vrices (ρ=0.3; p<0.05). No significnt correltion ws found between the AAR nd the number of ultrsonogrphic signs. Endoscopy None of the studied WD ptients suffered from vricel bleeding. However, grde 1-2 esophgel vrices were present in 47.8% of ptients with the neurologicl phenotype (Tble V). In heptic WD, grde 1-3 esophgel vrices were detected in 36.9% of ptients. Esophgel vrices were present in one symptomtic ptient dignosed through fmily screening (Tble V). Neither portlhypertensive gstropthy nor gstric vrices were detect- Muttion Exon Nucleotide chnge n of llelles Frequency (%) p.h1069q 14 c.3207c>a p.q1351x 20 c.4051c>t p.a1135fs 15 c.3402delc p.g1341d 20 c.4022g>a p.p1273l 18 c.3818c>t p.v1217_l1218del 17 c.3649_3654del p.ivs16-2a>g 17 c a>g p.g1186c 16 c.3556g>t p.g1158fs 16 c.3472_3482del p.w1353s 20 c.4058g>c p.i1148t 16 c.3443t>c p.r969fs 13 c.2905delc p.q544x 4 c.1630c>t p.a1135t 15 c.3403g>a The dt do not totl 100% s pthogenic muttions were not lwys identified in both lleles in ll 53 ptients. 26 Functionl Neurology 2014; 29(1): 23-29
5 Liver involvement in neurologicl form of Wilson s disese Tble III - Liver function tests nd indirect mrkers of liver fibrosis in ptients with Wilson s disese. (n = 23) (n = 19) (n = 11) ALT, IU/L (norml: 0-38), medin (IQR) 23.0 (19.0) 53.0 (51.0) 29.4 (29.0) Ptients with elevted ALT, n (%) 7 (30.4) 12 (63.2) 3 (27.3) AST, IU/L (norml: 0-40), medin (IQR) 27.0 (23.4) 46.0 (24.0) 30.0 (15.0) Ptients with elevted AST, n (%) 7 (30.4) 12 (63.2) 1 (9.1) GGTP (norml: ), medin (IQR) 35.9 (22.2) (86.4) 42.0 (48.2) Ptients with elevted GGTP, n (%) 4 (17.4) 14 (73.7) 3 (27.3) Bilirubin in mg/dl (norml: ), medin (IQR) 1.1 (0.3) 1.3 (1.0) 1.1 (0.2) Ptients with elevted bilirubin, n (%) 8 (34.8) 10 (52.6) 0 Serum lbumin in g/dl (norml: ), men ± SD 3.7 ± ± ± 0.8 Ptients with decresed serum lbumin, n (%) 9 (39.1) 8 (42.1) 1 (9.1) INR rtio (norml ), men ± SD 1.2 ± ± ± 0.2 Ptients with elevted INR, n (%) 15 (65.2) 9 (47.4) 0 Pltelet count x10 9 /L (norml: ), medin (IQR) (97.0) (128.0) (84.0),b Ptients with decresed pltelet count, n (%) 12 (52.2) 12 (63.2) 0 AAR >1, n (%) 16 (69.6) 10 (52.6) 6 (54.5) APRI > 1, n (%) 8 (34.8) 9 (47.4) 0 Abbrevitions: SD=stndrd devition; IQR=interqurtile rnge; AST= sprgine minotrnsferse; ALT=lnine minotrnsferse; GGTP=gmmglutmyl trnspeptidse; INR=interntionl normlized rtio; AAR=sprgine minotrnsferse/lnine minotrnsferse rtio; APRI= AST to pltelet rtio index. p<0.05 for the comprison with the heptic group; b p<0.05 for the comprison with the neurologicl group. Student s t-test or Mnn-Whitney U test for normlly/not normlly distributed vribles, respectively. Ctegoricl vribles were compred between groups by Fisher s exct test. Tble IV - Prevlence of ultrsonogrphic signs of liver cirrhosis in ptients with Wilson s disese. (n=23) (n=19) (n=11) Irregulr surfce, n (%) 15 (65.2) 7 (36.8) 0 Prenchyml inhomogeneity, n (%) 21(91.3) 10 (52.6) 3 (27.3) Collterl circultion, n (%) 2 (8.7) 2 (10.5) 0 Free peritonel fluid, n (%) 3 (13.0) 5 (26.3) 1 (9.1) Enlrgement of the spleen, n (%) 7 (30.4) 7 (36.8) 1 (9.1) Dilted portl vein, n (%) 11 (47.8) 11 (57.9) 1 (9.1) Decresed portl vein flow, n (%) 8 (34.8) 9 (47.4) 2 (18.2) p<0.05 for the comprison with the heptic group; ctegoricl vribles were compred between the heptic nd the neurologicl group by Fisher s exct test. Tble V - Prevlence of esophgel vrices. (n=23) (n=19) (n=11) Vrices grde 1; n (%) 8 (34.8) 4 (21.1) 1 (9.1) Vrices grde 2; n (%) 3 (13.0) 2 (10.5) 0 Vrices grde 3; n (%) 0 1 (5.3) 0 Itlin Liver Cirrhosis Project (ILCP) criteri were pplied to stge esophgel vrices. Functionl Neurology 2014; 29(1):
6 A. Przybylkowski et l. ed in ny ptient. Presence of esophgel vrices correlted significntly with number of ultrsonogrphic signs (s bove). Correltions with single ultrsonogrphic signs were significnt for liver homogeneity: ρ=0.4, p<0.05, collterl circultion: ρ=0.4, p<0.05, nodulr surfce: ρ=0.3, p<0.05, nd dilted portl vein: ρ=0.3, p<0.05. A significnt correltion ws lso found between esophgel vrices nd APRI 1.0: ρ=0.4, p<0.05. Discussion Although WD is single gene disorder, it is highly heterogeneous in its mnifesttions. The bsis of this phenotypic vrition is uncler s of yet. Thus when ptient is clssified s hving neurologicl WD with no clinicl evidence of liver disese, it is not known whether the ptient hrbors miniml liver involvement or, t the other extreme, dvnced liver disese tht is not reveled by stndrd criteri (i.e., liver function tests, liver synthetic function or clinicl signs of portl hypertension). In this series of consecutively evluted WD ptients, high prevlence of surrogte signs of dvnced liver disese ws found mong ll the ptients with symptomtic disese. It is importnt to note tht ptients with neurologicl WD nd no overt clinicl signs of liver disese hd high prevlence of surrogte mrkers of cirrhosis. It is suggested tht neurologicl symptoms in Wilsonin ptients typiclly develop secondry to liver involvement (Hrris et l., 2007). However, the true prevlence nd stging of liver disese mong ptients with neurologicl symptomtology re not yet clerly defined. In one utopsy study, heptitis nd micro-/mcronodulr cirrhosis were observed in ll ptients with neurologicl presenttion of the disese (Meenkshi-Sundrm et l., 2008). In nother cohort of 30 ptients, cirrhosis ws lso dignosed in ll the ptients presenting neurologicl symptoms; however, this group comprised only three subjects (Gow et l., 2000). Detection of cirrhosis is crucil for tretment plnning (qulifiction for liver trnsplnttion) nd from the perspective of surveillnce for cirrhosis complictions such s portl hypertension. Anlysis of deths in WD reveled tht liver filure nd vricel bleeding re common cuses (Wlshe, 2007; Czlonkowsk et l., 2005). USG-bsed dignosis of liver cirrhosis cn be bsed on heptic nd extr-heptic signs, nd the ccurcy of USG vries cross different studies lso becuse of the different prmeters exmined (Aube et l., 1999). There is no pproved score for ultrsonogrphic dignosis of cirrhosis, thus in common prctice the dignosis is mde t the exmining physicin s discretion (Bonekmp et l., 2009). In the present study, it ws decided on the bsis of the uthors experience tht the presence of t lest three ultrsonogrphic signs (one of which must be nodulr surfce of the liver) is relible for liver cirrhosis dignosis. Applying this criterion, liver cirrhosis ws observed in 11 of the 23 (47.8%) neurologicl ptients. All of them hd bnorml liver function tests nd in ll of them esophgel vrices were detected. Interestingly, mong 11 reltives who hd never sought medicl dvice for heptic or neurologicl problems, subtle liver involvement signs (nd even esophgel vrices in one cse) were present. This observtion strongly supports the ide tht the fmily members of newly dignosed WD ptients should be screened s soon s possible nd immeditely strted on nticopper therpy if the dignosis of WD is confirmed in them. At present, liver biopsy is still the reference stndrd for the ssessment nd stging of liver disese. Therefore, n obvious limittion of the present study is the lck of verifiction of the exmined surrogte mrkers of liver cirrhosis with histologicl ssessment of the liver prenchym. In this study, liver biopsy ws not performed routinely in ll the WD ptients. However biopsy confirmtion of cirrhosis is not mndtory if cler signs of cirrhosis (scites, cogulopthy, shrunken nodulr-ppering liver on imging studies) re present (Schuppn nd Afdhl, 2008). Therefore, in some WD cses, conventionl ultrsound exmintion in combintion with endoscopy nd lbortory test results my be sufficient to dignose liver cirrhosis. In conclusion, using lbortory mrkers, ultrsonogrphic signs or endoscopy, cirrhosis ws dignosed in 47.8% of newly dignosed ptients with the neurologicl form of WD. Some of them hd liver dysfunction signs in their medicl history, but hd not been further evluted. In every ptient with neurologicl WD, there ws t lest one ultrsonogrphic sign of dvnced liver disese. These results indicte the need for detiled ssessment of the liver in ll newly dignosed ptients with neurologicl presenttion of WD even if they do not show obvious heptic signs nd symptoms. Creful observtion of liver function in these cses is essentil in order to prevent severe complictions (e.g. vricel bleeding) nd for tretment strtegy. Acknowledgments: This study ws supported by The Ntionl Science Centre (grnt no. NN ). References Al A, Wlker AP, Ashkn K, et l (2007). Wilson's disese. Lncet 369: Aube C, Oberti F, Korli N, et l (1999). Ultrsonogrphic dignosis of heptic fibrosis or cirrhosis. J Heptol 30: Aube C, Winkfield B, Oberti F, et l (2004). New Doppler ultrsound signs improve the non-invsive dignosis of cirrhosis or severe liver fibrosis. Eur J Gstroenterol Heptol 16: Bonekmp S, Kmel I, Solg S, et l (2009). Cn imging modlities dignose nd stge heptic fibrosis nd cirrhosis ccurtely? J Heptol 50: Członkowsk A, Trnck B, Litwin T, et l (2005). Wilson's disese-cuse of mortlity in 164 ptients during observtion period. J Neurol 252: D'Amico G, Luc A (1997). Nturl history. Clinicl-hemodynmic correltions. Prediction of the risk of bleeding. Billieres Clin Gstroenterol 11: Ferenci P, Cc K, Loudinos G, et l (2003). Dignosis nd 28 Functionl Neurology 2014; 29(1): 23-29
7 Liver involvement in neurologicl form of Wilson s disese phenotypic clssifiction of Wilson disese. Liver Int 23: Frnk K, Linhrt P, Kortsik C, et l (1986). [Sonogrphic determintion of spleen size: norml dimensions in dults with helthy spleen]. Ultrschll Med 7: Gow PJ, Smllwood RA, Angus PW, et l (2000). Dignosis of Wilson's disese: n experience over three decdes. Gut 46: Goyl N, Jin N, Rchplli V, et l (2009). Non-invsive evlution of liver cirrhosis using ultrsound. Clin Rdiol 64: Hrris S, Nin HV, Siddique S (2007). Wilson's disese. Lncet 369: Mnning DS, Afdhl NH (2008) Dignosis nd quntittion of fibrosis. Gstroenterology 134: Meenkshi-Sundrm S, Mhdevn A, Tly AB, et l (2008). Wilson's disese: clinico-neuropthologicl utopsy study. J Clin Neurosci 15: Merkel C, Zoli M, Siringo S, et l (2000). Prognostic indictors of risk for first vricel bleeding in cirrhosis: multicenter study in 711 ptients to vlidte nd improve the North Itlin Endoscopic Club (NIEC) index. Am J Gstroenterol 95: Schuppn D, Afdhl NH (2008). Liver cirrhosis. Lncet 371: Tnzi RE, Petrukhin K, Chernov I, et l. (1993). The Wilson disese gene is copper trnsporting ATPse with homology to the Menkes disese gene. Nt Genet 5: Wi CT, Greenson JK, Fontn RJ et l (2003). A simple noninvsive index cn predict both significnt fibrosis nd cirrhosis in ptients with chronic heptitis C. Heptology 38: Wlshe JM (2007). Cuse of deth in Wilson disese. Mov Disord 22: Wlshe JM, Wldenström E, Sms V, et l (2003). Abdominl mlignncies in ptients with Wilson's disese. QJM 96: Functionl Neurology 2014; 29(1):
Clinical Study Report Synopsis Drug Substance Naloxegol Study Code D3820C00018 Edition Number 1 Date 01 February 2013 EudraCT Number
EudrCT Number 2012-001531-31 A Phse I, Rndomised, Open-lbel, 3-wy Cross-over Study in Helthy Volunteers to Demonstrte the Bioequivlence of the Nloxegol 25 mg Commercil nd Phse III Formultions nd to Assess
More informationResults of the Tokyo Consensus Meeting Tokyo Guidelines
J Heptobiliry Pncret Surg (2007) 14:114 121 DOI 10.1007/s00534-006-1163-8 Results of the Tokyo Consensus Meeting Tokyo Guidelines Toshihiko Myumi 1, Tdhiro Tkd 2, Yoshifumi Kwrd 3, Yuji Nimur 4, Mshiro
More informationCase Report INTRODUCTION CASE REPORT. pissn eissn X
pissn 2287-2728 eissn 2287-285X Cse Report Clinicl nd Moleculr Heptology 2018;24:424-429 Complete cure of dvnced heptocellulr crcinom with right drenl glnd metstsis nd portl vein thrombosis by multiple
More informationFeeding state and age dependent changes in melaninconcentrating hormone expression in the hypothalamus of broiler chickens
Supplementry Mterils Epub: No 2017_23 Vol. 65, 2018 https://doi.org/10.183/bp.2017_23 Regulr pper Feeding stte nd ge dependent chnges in melninconcentrting hormone expression in the hypothlmus of broiler
More informationAssessment of Depression in Multiple Sclerosis. Validity of Including Somatic Items on the Beck Depression Inventory II
Assessment of Depression in Multiple Sclerosis Vlidity of Including Somtic Items on the Beck Depression Inventory II Peggy Crwford, PhD; Noh J. Webster, MA Signs nd symptoms of multiple sclerosis (MS)
More informationBody mass index, waist-to-hip ratio, and metabolic syndrome as predictors of middle-aged men's health
Originl Article - Sexul Dysfunction/Infertility pissn 2005-6737 eissn 2005-6745 Body mss index, wist-to-hip rtio, nd metbolic syndrome s predictors of middle-ged men's helth Jung Hyun Prk *, In-Chng Cho
More informationSupplementary Online Content
Supplementry Online Content Zulmn DM, Pl Chee C, Ezeji-Okoye SC, et l. Effect of n intensive outptient progrm to ugment primry cre for high-need Veterns Affirs ptients: rndomized clinicl tril. JAMA Intern
More informationImpact of Positive Nodal Metastases in Patients with Thymic Carcinoma and Thymic Neuroendocrine Tumors
Originl Article Impct of Positive Nodl Metstses in Ptients with Thymic Crcinom nd Thymic Neuroendocrine Tumors Benny Weksler, MD, Anthony Holden, MD, nd Jennifer L. Sullivn, MD Introduction: Thymic crcinoms
More informationSupplementary Online Content
Supplementry Online Content Rieckmnn N, Kronish IM, Shpiro PA, Whng W, Dvidson KW. Serotonin reuptke inhibitor use, depression, nd long-term outcomes fter n cute coronry : prospective cohort study. JAMA
More informationCorrelation between CT features and liver function and p53 expression in hepatitis, cirrhosis and hepatocellular carcinoma
ONCOLOGY LETTERS Correltion between CT fetures nd liver function nd p53 expression in heptitis, cirrhosis nd heptocellulr crcinom YAHUI HU, JING WU, SHA LI nd XIAOXIAO ZHAO Deprtment of Nucler Medicine,
More informationAnalysis of Regulatory of Interrelated Activity of Hepatocyte and Hepatitis B Viruses
Interntionl Journl of Biomedicl Mterils Reserch 8 6(): -7 http://www.sciencepublishinggroup.com/j/ijbmr doi:.648/j.ijbmr.86. ISSN: 33-756 (Print) ISSN: 33-7579 (Online) Anlysis of Regultory of Interrelted
More informationMuhammad Shoaib, Muhammad Usman, Rabia Fatima, Sajid Aziz, Muhammad Wasif Malik, Muhammad Javaid Asad and Sikandar Khan Sherwani
Americn-Eursin Journl of Toxicologicl Sciences 7 (4): 214-219, 2015 ISSN 2079-2050 IDOSI Publictions, 2015 DOI: 10.5829/idosi.ejts.2015.7.4.9447 Reltionship Among Alnine Amino-Trnsferse (ALT), Prtil Thromboplstin
More informationStart ORKAMBI today. INDICATIONS AND USAGE IMPORTANT SAFETY INFORMATION. Sydney Age 4
F O R H E A L T H C A R E P R O F E S S I O N A L S For ptients ge 2 yers nd older who re homozygous for the F508del muttion 1,2 Modify the course. Strt tody. Sydney Age 4 F508del/F508del INDICATIONS AND
More informationHepatitis A virus (HAV) infection contributes approximately
Multiple Fctors Contribute to Positive Results for Heptitis A Virus Immunoglobulin M Antibody Adnn Altoom, MD, PhD; M. Qsim Ansri, MD; Jennifer Cuthbert, MD Context. In the United Sttes, successful vccintion
More informationBENIGN ulceration along the greater curvature of the pars media of the
BENIGN ULCERS OF THE GREATER CURVATURE OF THE STOMACH Report of Two Cses CHARLES H. BROWN, M.D. Deprtment of Gstroenterology nd ANTHONY D. INTRIERE, M.D.* BENIGN ulcertion long the greter curvture of the
More informationPrognostic significance of pretreatment serum levels of albumin, LDH and total bilirubin in patients with nonmetastatic
Crcinogenesis, 2015, Vol. 36, No. 2, 243 248 doi:10.1093/crcin/bgu247 Advnce Access publiction December 18, 2014 Originl Mnuscript originl mnuscript Prognostic significnce of pretretment serum levels of
More informationRisks for All-Cause Mortality: Stratified by Age, Estimated Glomerular Filtration Rate and Albuminuria
Clinicl Prctice: Mini-Review Received: My 20, 2016 Accepted fter revision: December 14, 2016 Published online: Jnury 27, 2017 Risks for All-Cuse Mortlity: Strtified by Age, Estimted Glomerulr Filtrtion
More informationDose-dependent effect of daptomycin on the artificial prolongation of prothrombin time in coagulation abnormalities: in vitro verification
Hshimoto et l. BMC Phrmcology nd Toxicology (2017) 18:74 DOI 10.1186/s40360-017-0180-3 RESEARCH ARTICLE Open Access Dose-dependent effect of dptomycin on the rtificil prolongtion of prothrombin time in
More informationSingle-Molecule Studies of Unlabelled Full-Length p53 Protein Binding to DNA
Single-Molecule Studies of Unlbelled Full-Length p53 Protein Binding to DNA Philipp Nuttll, 1 Kidn Lee, 2 Pietro Ciccrell, 3 Mrco Crminti, 3 Giorgio Ferrri, 3 Ki- Bum Kim, 2 Tim Albrecht 1* 1 Imperil College
More informationFactors affecting screening for hepatocellular carcinoma
204 Al Hsni F, et l., 2014; 13 (2): 204-210 ORIGINAL ARTICLE Mrch-April, Vol. 13 No. 2, 2014: 204-210 Fctors ffecting screening for heptocellulr crcinom Frh Al Hsni,* Mrin Knoepfli, Armin Gemperli, Attil
More informationR Martino 1, P Romero 1, M Subirá 1, M Bellido 1, A Altés 1, A Sureda 1, S Brunet 1, I Badell 2, J Cubells 2 and J Sierra 1
Bone Mrrow Trnsplnttion, (1999) 24, 283 287 1999 Stockton Press All rights reserved 0268 3369/99 $12.00 http://www.stockton-press.co.uk/bmt Comprison of the clssic Glucksberg criteri nd the IBMTR Severity
More informationClinical statistics analysis on the characteristics of pneumoconiosis of Chinese miner population
Originl Article Clinicl sttistics nlysis on the chrcteristics of pneumoconiosis of Chinese miner popultion Mei-Fng Wng 1 *, Run-Ze Li 2 *, Ying Li 2, Xue-Qin Cheng 1, Jun Yng 1, Wen Chen 3, Xing-Xing Fn
More informationEfficacy of Pembrolizumab in Patients With Advanced Melanoma With Stable Brain Metastases at Baseline: A Pooled Retrospective Analysis
Efficcy of Pembrolizumb in Ptients With Advnced Melnom With Stble Brin Metstses t Bseline: A Pooled Retrospective Anlysis Abstrct 1248PD Hmid O, Ribs A, Dud A, Butler MO, Crlino MS, Hwu WJ, Long GV, Ancell
More informationRecall Bias in Childhood Atopic Diseases Among Adults in The Odense Adolescence Cohort Study
Syddnsk Universitet Recll Bis in Childhood Atopic Diseses Among Adults in The Odense Adolescence Cohort Study Mørtz, Chrlotte G; Andersen, Klus Ejner; Bindslev-Jensen, Crsten Published in: Act Dermto-Venereologic
More informationSummary of Package Insert 1
Summry of Pckge Insert 1 For Sttes with Non-Published Policies Indictions Non-infected prtil nd full-thickness skin ulcers due to VSU 2 of greter thn 1 month durtion nd which hve not dequtely responded
More informationof comorbid conditions, interventions Diagnosis and treatment, treatment reduction of risk factors for CVD to slow disease progression,
Tble 5.1. NKF Clssifiction of Chronic Kidney Disese nd Clinicl Fetures Stge Description GFR (ml/ min/1.73 m 2 ) U.S. Prevlence, b # Affected (%) Clinicl Fetures Action Pln c At incresed risk for CKD >60
More informationRelationship between serum irisin, glycemic indices, and renal function in type 2 diabetic patients
J Renl Inj Prev. 2017; 6(2): 88-92. http://journlrip.com Journl of Renl Injury Prevention DOI: 10.15171/jrip.2017.17 Reltionship between serum irisin, glycemic indices, nd renl function in type 2 dibetic
More informationThe burden of cirrhosis and impact of universal coverage public health care system in Thailand: Nationwide study
862 Poovorwn K, et l., 2015; 14 (6): 862-868 ORIGINAL ARTICLE November-December, Vol. 14 No. 6, 2015: 862-868 The burden of cirrhosis nd impct of universl coverge public helth cre system in Thilnd: Ntionwide
More informationInvasive Pneumococcal Disease Quarterly Report. July September 2017
Invsive Pneumococcl Disese Qurterly Report July September 2017 Prepred s prt of Ministry of Helth contrct for scientific services by Rebekh Roos Helen Heffernn October 2017 Acknowledgements This report
More informationRheumatoid-susceptible alleles of HLA-DRB 1 are genetically recessive to non-susceptible alleles in the progression of bone destruction in the wrists
Annls of the Rheumtic Diseses 1994; 53: 587-592 587 Deprtment of Orthopedic Surgery, Knsi Medicl University, Otokoym Hospitl, Kyoto, Jpn Y Tod Y Mori Deprtment of Orthopedic Surgery, Knsi Medicl University,
More informationClinical manifestations in patients with alpha-fetoprotein producing gastric cancer
Curr Oncol, Vol. 21, pp. e394-399; doi: http://dx.doi.org/10.3747/co.21.1768 CLINICAL MANIFESTATIONS IN AFP PRODUCING GASTRIC CANCER ORIGINAL ARTICLE Clinicl mnifesttions in ptients with lph-fetoprotein
More informationPNEUMOVAX 23 is recommended by the CDC for all your appropriate adult patients at increased risk for pneumococcal disease 1,2 :
PNEUMOVAX 23 is recommended y the CDC for ll your pproprite dult ptients t incresed risk for pneumococcl disese 1,2 : Adults ged
More informationMetabolic Syndrome and Health-related Quality of Life in Obese Individuals Seeking Weight Reduction
Metbolic Syndrome nd Helth-relted Qulity of Life in Obese Individuls Seeking Weight Reduction Adm Gilden Tsi 1, Thoms A. Wdden 1, Dvid B. Srwer 1, Robert I. Berkowitz 1, Leslie G. Womble 1, Louise A. Hesson
More informationDiabetes mellitus secondary to pancreatic diseases (type 3c): The effect of smoking on the exocrine endocrine interactions of the pancreas
764062DVR0010.1177/1479164118764062Dibetes & Vsculr Disese ReserchŚliwińsk-Mossoń et l. reserch-rticle2018 Originl Article Dibetes mellitus secondry to pncretic diseses (type 3c): The effect of smoking
More informationCME/SAM. Study on Hyperuricemia in HBV-Associated Glomerulonephritis
AJCP / Originl Article Study on Hyperuricemi in HBV-Associted Glomerulonephritis Yongze Zhung, MD, PhD, 1 Yingho Yu, MD, PhD, 2 Yingfng Hung, MD, 3 nd Xiorong Zhong, MD 1 From the 1 Deprtment of Nephrology,
More informationENERGY CONTENT OF BARLEY
ENERGY CONTENT OF BARLEY VARIATION IN THE DIETARY ENERGY CONTENT OF BARLEY Shwn Firbirn, John Ptience, Hnk Clssen nd Ruurd Zijlstr SUMMARY Formultion of commercil pig diets requires n incresing degree
More informationA Comparison of Serum Magnesium Level in Pregnant Women with and without Gestational Diabetes Mellitus (GDM)
Brief Report J Bbol Univ Med Sci Vol 18, Issu 12; Dec 2016. P:71-75 A Comprison of Serum Mgnesium Level in Pregnnt Women with nd without Gesttionl Dibetes Mellitus (GDM) Z. Bouzri (MD) 1, F. Elmi(MD) 2,
More informationHandgrip exercise elevates basilic venous hemodynamic parameters in healthy subjects
interntionl journl of nursing sciences 1 (2014) 389e393 Avilble online t www.sciencedirect.com ScienceDirect journl homepge: http://www.elsevier.com/journls/interntionljournl-of-nursing-sciences/2352-0132
More informationAnalysis of alternatives for insulinizing patients to achieve glycemic control and avoid accompanying risks of hypoglycemia
284 Anlysis of lterntives for izing ptients to chieve glycemic control nd void ccompnying risks of hypoglycemi JIALIN GAO 1,2*, QIANYIN XIONG 1,2*, JUN MIAO 1*, YAO ZHANG 2,3, LIBING XIA 1, MEIQIN LU 1,
More informationSafety and Tolerability of Subcutaneous Sarilumab and Intravenous Tocilizumab in Patients With RA
Sfety nd Tolerbility of Subcutneous Srilumb nd Intrvenous Tocilizumb in Ptients With RA Pul Emery, 1 Jun Rondon, 2 Anju Grg, 3 Hubert vn Hoogstrten, 3 Neil M.H. Grhm, 4 Ming Liu, 4 Nncy Liu, 3 Jnie Prrino,
More informationOpioid Use and Survival at the End of Life: A Survey of a Hospice Population
532 Journl of Pin nd Symptom Mngement Vol. 32 No. 6 December 2006 NHPCO Originl Article Opioid Use nd Survivl t the End of Life: A Survey of Hospice Popultion Russell K. Portenoy, MD, Un Sibircev, BA,
More informationAbstract. Background. Aim. Patients and Methods. Patients. Study Design
Impct of the Use of Drugs nd Substitution Tretments on the Antivirl Tretment of Chronic Heptitis C: Anlysis of Complince, Virologicl Response nd Qulity of Life (CHEOBS). Melin, 1 J.-. Lng, D. Ouzn, 3 M.
More informationCheckMate 153: Randomized Results of Continuous vs 1-Year Fixed-Duration Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer
CheckMte 53: Rndomized Results of Continuous vs -Yer Fixed-Durtion Nivolumb in Ptients With Advnced Non-Smll Cell Lung Cncer Abstrct 297O Spigel DR, McCleod M, Hussein MA, Wterhouse DM, Einhorn L, Horn
More informationRisk Factors and Outcomes Stratified by Severity of Acute Kidney Injury in Malaria
Risk Fctors nd Outcomes Strtified by Severity of Acute Kidney Injury in Mlri Kvith Srvu 1 *, Kumr Rishikesh 1, Chirg R. Prikh 2 * 1 Deprtment of Medicine, Ksturb Medicl College, Mnipl University, Mnipl,
More informationOriginal Article. T Akter 1, N Islam 2, MA Hoque 3, S Khanam 4, HA khan 5, BK Saha 6. Abstract:
Fridpur Med. Coll. J. 214;9(2):61-67 Originl Article Nebuliztion by Isotonic Mgnesium Sulphte Solution with Provide Erly nd Better Response s Compred to Conventionl Approch ( Plus Norml Sline) in Acute
More information27 June Bmnly L. WALTER ET AL.: RESPONSE OF CERVICAL CANCERS TO IRRADIATION
27 June 1964 Bmnly MEDICAL JOURNAL L. WALTER ET AL.: RESPONSE OF CERVICAL CANCERS TO IRRADIATION x 1,638.) FIG. 2.-Foci of sme tumour s in Fig. 1 contining vible tumour cells with scnty cytoplsm, reltively
More informationOne of the most important biological mechanisms of
Brief Report Serum Thymidine Kinse 1 Activity in the Prognosis nd Monitoring of Chemotherpy in Lung Cncer Ptients: A Brief Report Benjmin Nismn, PhD,* Hovv Nechushtn, MD, PhD,* Him Birn, MD, Hds Gntz-Sorotsky,
More informationA review of the patterns of docetaxel use for hormone-resistant prostate cancer at the Princess Margaret Hospital
MEDICAL ONCOLOGY A review of the ptterns of docetxel use for hormone-resistnt prostte cncer t the Princess Mrgret Hospitl S.N. Chin MD,* L. Wng MSc, M. Moore MD,* nd S.S. Sridhr MD MSc* ABSTRACT Bckground
More informationMultiple sclerosis (MS) affects approximately. Triaging Patients with Multiple Sclerosis in the Emergency Department. Room for Improvement
Systemtic Review of Tools for Anxiety in MS MS CARE DELIVERY: CHALLENGES AND INVATIONS Triging Ptients with Multiple Sclerosis in the Emergency Deprtment Room for Improvement Heshm Abboud, MD, PhD; Krin
More informationImpact of left ventricular hypertrophy on survival in end-stage renal disease
Kidney Interntionl, Vol. 36 (1989), pp. 286 290 Impct of left ventriculr hypertrophy on survivl in end-stge renl disese JONATHAN S. SILBERBERG, PAUL E. BARRE, SARAH S. PRICHARD, nd ALLAN D. SNIDERMAN Divisions
More informationJournal of Hainan Medical University 2017; 23(2): Journal of Hainan Medical University.
Journl of Hinn Medicl University 2017; 23(2): 151-155 151 Journl of Hinn Medicl University http://www.hnykdxxb.com Reltionship between DEXA bone minerl density mesurement results nd serum cytokines s well
More informationC reactive protein: an aid to assessment and
C rective protein: n id to ssessment nd monitoring of cute pncretitis J Clin Pthol 1984;37:27-211 AD MAYR,* MJ McMAHON,* MARGART BOWN,t H COOPRt From the *University Deprtment ofsurgery, Generl Infrmry,
More informationNon-invasive Diagnosis of Liver Clinical Condition by Real-time Tissue Elastography and Shear Wave Measurement : Get More Accessible by One Probe
XXXXXXXXXX Non-invsive Dignosis of Liver Clinicl Condition y Rel-time Tissue Elstogrphy nd Sher Wve Mesurement : Get More Accessile y One Proe Norihis Yd Mstoshi Kudo Deprtment of Gstroenterology nd Heptology,
More informationIntroduction. These patients benefit less from conventional chemotherapy than patients identified as MMR proficient or microsatellite stable 3-5
Nivolumb + Ipilimumb Combintion in Ptients With DNA Mismtch Repir-Deficient/Microstellite Instbility-High Metsttic Colorectl Cncer: First Report of the Full Cohort From CheckMte-142 Abstrct 553 André T,
More informationA cross-sectional and follow-up study of leukopenia in tuberculosis patients: prevalence, risk factors and impact of anti-tuberculosis
Originl Article A cross-sectionl nd follow-up study of leukopeni in tuberculosis ptients: prevlence, risk fctors nd impct of nti-tuberculosis tretment Fei-Shen Lin 1 *, Mei-Ying Wu 2 *, Wen-Jun Tu 3, Hong-Qiu
More informationSerum γ-glutamyltransferase: Independent Predictor of Risk of Diabetes, Hypertension, Metabolic Syndrome, and Coronary Disease
nture publishing group Serum γ-glutmyltrnsferse: Independent Predictor of Risk of Dibetes, Hypertension, Metbolic Syndrome, nd Coronry Disese Altn Ont 1, Güny Cn 2, Ender Örnek 3, Gökhn Çiçek 4, Erkn Ayhn
More informationPredictors of Hospitalization in Male Marine Corps Recruits with Exertional Heat Illness
MILITARY MEDICINE, 169, 3:169, 2004 Predictors of Hospitliztion in Mle Mrine Corps Recruits with Exertionl Het Illness Gurntor: COL John W. Grdner, MC FS USA Contributors: Shilp Hkre, DrPH; COL John W.
More informationCharacteristics of hip involvement in patients with ankylosing spondylitis in Korea
ORIGINAL ARTICLE Koren J Intern Med 2017;32:158-164 Chrcteristics of hip involvement in ptients with nkylosing spondylitis in Kore Hyemin Jeong, Yeong Hee Eun, In Young Kim, Hyungjin Kim, Jejoon Lee, Eun-Mi
More informationLipase and Pancreatic Amylase Activities in Tissues and in Patients with Hyperamylasemia
CLINICAL CHEMISTRY Originl Article Lipse nd Pncretic Amylse Activities in Tissues nd in Ptients with Hypermylsemi FRED APPLE, PH.D, PETER BENSON, M.D., LYNNE PREESE, MT, M.B.A., STEVEN EASTEP, M.D., LAURA
More informationOriginal Research Article. Dement Geriatr Cogn Disord 2007;24: DOI: /
Originl Reserch Article Dement Geritr Cogn Disord 2007;24:288 293 DOI: 10.1159/000107592 Accepted: June 26, 2007 Published online: August 24, 2007 A Normtive Study of the Revised Hsegw Dementi Scle: Comprison
More informationHealth-Related Quality of Life and Symptoms of Depression in Extremely Obese Persons Seeking Bariatric Surgery
Oesity Surgery, 15, 3-39 Helth-Relted Qulity of Life nd Symptoms of Depression in Extremely Oese Persons Seeking Britric Surgery Anthony N. Frictore, PhD; Thoms A. Wdden, PhD; Dvid B. Srwer, PhD; Myles
More informationGlobal Intellectual Deficits in Cystinosis
Americn Journl of Medicl Genetics 49:83-87 (1994) Globl Intellectul Deficits in Cystinosis Brbr L.H. Willims, Jerry A. Schneider, nd Doris A. Truner Deprtments of Neurosciences (B.L.H.W.. D.A.T.) nd Peditrics
More informationComparative effectiveness of the tumour diagnostics,
Gut, 1987, 28, 323-329 Comprtive effectiveness of the tumour dignostics, C 19-9, C 125 nd crcinoembryonic ntigen in ptients with diseses of the digestive system K SKMOTO, Y HG, R YOSHIMR, H GMI, Y YOKOYM,
More informationEOSINOPHILIC PLEURAL EFFUSION IN ADULTS AT SRINAGARIND HOSPITAL
EOSINOPHILIC PLEURAL EFFUSION IN ADULTS AT SRINAGARIND HOSPITAL Wip Reechipichitkul nd Kittisk Chueskoolvnich Deprtment of Medicine, Sringrind Hospitl, Fculty of Medicine, Khon Ken University, Khon Ken,
More informationJournal of Cystic Fibrosis 1 (2002)
Journl of Cystic Fibrosis 1 (2002) 276 280 Assessment of nutritionl sttus in children with cystic fibrosis: conventionl nthropometry nd bioelectricl impednce nlysis. A cross-sectionl study in Dutch ptients,
More informationComparison of three simple methods for the
J. clin. Pth. (1967), 2, 5 Comprison of three simple methods for the ssessment of 'free' thyroid hormone T. M. D. GIMLETTE1 From the Rdio-Isotope Lbortory, St. Thoms's Hospitl, London SYNOPSIS A dilysis
More informationEFFECTS OF INGREDIENT AND WHOLE DIET IRRADIATION ON NURSERY PIG PERFORMANCE
Swine Dy 21 EFFECTS OF INGREDIENT AND WHOLE DIET IRRADIATION ON NURSERY PIG PERFORMANCE J. M. DeRouchey, M. D. Tokch, J. L. Nelssen, R. D. Goodbnd, S. S. Dritz 1, J. C. Woodworth, M. J. Webster, B. W.
More informationSYNOPSIS Final Abbreviated Clinical Study Report for Study CA ABBREVIATED REPORT
Finl Arevited Clinicl Study Report Nme of Sponsor/Compny: Bristol-Myers Squi Ipilimum Individul Study Tle Referring to the Dossier (For Ntionl Authority Use Only) Nme of Finished Product: Yervoy Nme of
More informationEffects of physical exercise on working memory and prefrontal cortex function in post-stroke patients
Effects of physicl exercise on working memory nd prefrontl cortex function in post-stroke ptients M Moriy, C Aoki, K Sktni Grdute School of Helth Sciences Reserch, Mjor of Physicl Therpy, TeikyoHeisei
More informationThe Association of Gender With Quality of Health in Peripheral Arterial Disease Following Peripheral Vascular Intervention
The Assocition of Gender With Qulity of Helth in Peripherl Arteril Disese Following Peripherl Vsculr Intervention Sudrshn Pudel, MD 1 ; Anwr Zitoun, MD 1 ; Sif Al-Njfi, MD 2 ; Ther Mus, MD 3 ; Susn Szpunr,
More informationBMI and Mortality: Results From a National Longitudinal Study of Canadian Adults
nture publishing group BMI nd Mortlity: Results From Ntionl Longitudinl Study of Cndin Adults Hether M. Orpn 1, Jen-Mrie Berthelot 2,3, Mrk S. Kpln 4, Dvid H. Feeny 5,6, Bentson McFrlnd 7 nd Nncy A. Ross
More informationTHE CHB TREATMENT GUIDELINE NAVIGATOR REVIEW AN ONLINE INTERACTIVE GUIDE FOR CLINICIANS FEATURING EXPERT AUDIO COMMENTARY
The Americn Assocition for the Study of Liver Diseses () nd the Europen Assocition for the Study of Liver Disese () provide clinicl prctice guidelines for the mngement nd tretment of chronic heptitis B
More informationOriginal Article Serum tumor markers used for predicting esophagogastric junction adenocarcinoma in esophageal malignancy
Int J Clin Exp Med 2016;9(6):11859-11864 www.ijcem.com /ISSN:1940-5901/IJCEM0025330 Originl Article Serum tumor mrkers used for predicting esophgogstric junction denocrcinom in esophgel mlignncy Yongkng
More informationHypertension, hyperinsulinaemia and obesity in middle-aged Finns with impaired glucose tolerance
Journl of Humn Hypertension (1998) 12, 265 269 1998 Stockton Press. All rights reserved 0950-9240/98 $12.00 ORIGINAL ARTICLE Hypertension, hyperinsulinemi nd obesity in middle-ged Finns with impired glucose
More informationXII. HIV/AIDS. Knowledge about HIV Transmission and Misconceptions about HIV
XII. HIV/AIDS Knowledge bout HIV Trnsmission nd Misconceptions bout HIV One of the most importnt prerequisites for reducing the rte of HIV infection is ccurte knowledge of how HIV is trnsmitted nd strtegies
More informationThe Acute Time Course of Concurrent Activation Potentiation
Mrquette University e-publictions@mrquette Exercise Science Fculty Reserch nd Publictions Exercise Science, Deprtment of 1-1-2010 The Acute Time Course of Concurrent Activtion Potentition Luke Grceu Mrquette
More informationEFFECTS OF AN ACUTE ENTERIC DISEASE CHALLENGE ON IGF-1 AND IGFBP-3 GENE EXPRESSION IN PORCINE SKELETAL MUSCLE
Swine Dy 22 Contents EFFECTS OF AN ACUTE ENTERIC DISEASE CHALLENGE ON IGF-1 AND IGFBP-3 GENE EXPRESSION IN PORCINE SKELETAL MUSCLE B. J. Johnson, J. P. Kyser, J. D. Dunn, A. T. Wyln, S. S. Dritz 1, J.
More informationDifferent type 2 diabetes risk assessments predict dissimilar numbers at high risk :
Reserch Benjmin J Gry, Richrd M Brcken, Dniel Turner, Kerry Morgn, Michel Thoms, Slly P Willims, Meurig Willims, Sm Rice nd Jeffrey W Stephens on behlf of the Prosiect Sir Gâr Group Different type 2 dibetes
More informationThe RUTHERFORD-2 trial in heterozygous FH: Results and implications
The RUTHERFORD-2 tril in heterozygous FH: Results nd implictions Slide deck kindly supplied s n eductionl resource by Professor Derick Rl MD PhD Crbohydrte & Lipid Metbolism Reserch Unit University of
More informationImpact of endoscopy-based research on quality of life in healthy volunteers
Online Submissions: http://www.wjgnet.com/17-9327office wjg@wjgnet.com doi:1.3748/wjg.v16.i4.467 World J Gstroenterol 21 Jnury 28; 16(4): 467-473 ISSN 17-9327 (print) 21 Bishideng. All rights reserved.
More informationWSU Tree Fruit Research and Extension Center, Wenatchee (509) ext. 265;
FINAL REPORT WTFRC Project # AH-1-5 WSU Project # 13C-355-3 Project title: PI: Orgniztion: Coopertors: of Sunburn in Apples with RAYNOX Lrry Schrder, Horticulturist WSU Tree Fruit Reserch nd Extension
More informationAmerican Joint Committee on Cancer Staging and Clinicopathological High-Risk Predictors of Ocular Surface Squamous Neoplasia
Americn Joint Committee on Cncer Stging nd Clinicopthologicl High-Risk Predictors of Oculr Surfce Squmous Neoplsi A Study From Tertiry Eye Center in Indi Sheetl Chuhn, MSc; Seem Sen, MD; Anjn Shrm, PhD;
More informationImpact of Pharmacist Intervention on Diabetes Patients in an Ambulatory Setting
Impct of Phrmcist Intervention on Dibetes Ptients in n Ambultory Setting Julie Stding, PhrmD, CDE, Jmie Herrmnn, PhrmD, Ryn Wlters, MS, Chris Destche, PhrmD, nd Aln Chock, PhrmD Dibetes is the seventh-leding
More informationA Comparative Study of Eating Habits and Food Intake in Women with Gestational Diabetes according to Early Postpartum Glucose Tolerance Status
Originl Article http://dx.doi.org/10.4093/dmj.2011.35.4.354 pissn 2233-6079 eissn 2233-6087 D I A B E T E S & M E T A B O L I S M J O U R N A L A Comprtive Study of Eting Hbits nd Food Intke in Women with
More informationHematology TOONYA TURNER. IDEXX Services: Senior Profile with Heartworm -Standard CBC. RBC M/µL. Hematocrit
TOONYA TURNER PET OWNER: TURNER SPECIES: Cnine BREED: GENDER: Femle AGE: 1 Yers PATIENT ID: 17047 Fmily Pet Helth Cre 3623 Indin Hills Rod Dectur, Albm 35603 256-341-0200 ACCOUNT #: 87040 ATTENDING VET:
More informationLung cancer is the leading cause of cancer death worldwide, EGFR Mutation and Brain Metastasis in Pulmonary Adenocarcinomas
Originl Article EGFR Muttion nd Brin Metstsis in Pulmonry Adenocrcinoms Dong-Yeop Shin, MD,* Im Il N, MD,* Cheol Hyeon Kim, MD, PhD, Sunhoo Prk, MD, PhD, HeeJong Bek, MD, PhD, nd Sung Hyun Yng, MD, PhD*
More informationEfficacy of Sonidegib in Patients With Metastatic BCC (mbcc)
AAD 216 eposter 3368 Efficcy of Sonidegib in Ptients With Metsttic BCC (mbcc) Colin Morton, 1 Michel Migden, 2 Tingting Yi, 3 Mnish Mone, 3 Dlil Sellmi, 3 Reinhrd Dummer 4 1 Stirling Community Hospitl,
More informationCommunity. Profile Big Horn County. Public Health and Safety Division
Community Helth Profile 2015 Big Horn County Public Helth nd Sfety Division Tble of Contents Demogrphic Informtion 1 Communicble Disese 3 Chronic Disese 4 Mternl nd Child Helth 10 Mortlity 12 Behviorl
More informationa a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a a
346 Cldwell SH, et l.,, 2009; 8 (4): 346 3 2 ORIGINAL ARTICLE October-December, Vol. 8 No.4, 2009: 346-352 NASH nd cryptogenic cirrhosis: A histologicl nlysis Stephen H. Cldwell,* Vness D. Lee,* Dvid E.
More informationThe accuracy of creatinine clearance with and without
Postgrd Med J (1991) 67, 42-46 ) The Fellowship of Postgrdute Medicine, 1991 The ccurcy of cretinine clernce with nd without urine collection s mesure of glomerulr filtrtion rte D.G. Wller,' J.S. Fleming,2
More informationJ Neurogastroenterol Motil, Vol. 24 No. 4 October, 2018
JNM J Neurogstroenterol Motil, Vol. 24 No. 4 October, 18 pissn: 93-879 eissn: 93-887 https://doi.org/1.556/jnm185 Journl of Neurogstroenterology nd Motility Originl Article Quntittive Anlysis of Distribution
More informationResults of improvement in adequacy of intermittent hemodialysis in uremic patients
314 Grzegorzewsk AE, et l. Roczniki Akdemii Medycznej w Biłymstoku Vol. 50, 2005 Annles Acdemie Medice Bilostocensis Results of improvement in dequcy of intermittent hemodilysis in uremic ptients Grzegorzewsk
More informationORIGINAL ARTICLE. Diagnostic Signs of Accommodative Insufficiency. PILAR CACHO, OD, ÁNGEL GARCÍA, OD, FRANCISCO LARA, OD, and M A MAR SEGUÍ, OD
1040-5488/02/7909-0614/0 VOL. 79, NO. 9, PP. 614 620 OPTOMETRY AND VISION SCIENCE Copyright 2002 Americn Acdemy of Optometry ORIGINAL ARTICLE Dignostic Signs of Accommodtive Insufficiency PILAR CACHO,
More informationEvaluation of the TEST 1 erythrocyte sedimentation rate system and intra- and inter-laboratory quality control using new latex control materials
Clin Chem Lb Med 2010;48(7):1043 1048 2010 by Wlter de Gruyter Berlin New York. DOI 10.1515/CCLM.2010.162 Evlution of the TEST 1 erythrocyte sedimenttion rte system nd intr- nd inter-lbortory qulity control
More informationStandardized Ultrasound Hepatic/Renal Ratio and Hepatic Attenuation Rate to Quantify Liver Fat Content: An Improvement Method
nture publishing group Open Stndrdized Ultrsound Heptic/Renl Rtio nd Heptic Attenution Rte to Quntify Liver Ft Content: An Improvement Method Ming-Feng Xi 1, Hong-Mei Yn 1, Wn-Yun He 2, Xio-Ming Li 1,
More informationGlucose is the most commonly used osmotic agent in
Peritonel Dilysis Interntionl, Vol. 32, pp. 545 551 doi: 10.3747/pdi.2011.00048 0896-8608/12 $3.00 +.00 Copyright 2012 Interntionl Society for Peritonel Dilysis ULTRAFILTRATION AND DIALYSIS ADEQUACY WITH
More information8/1/2017. Correlating Radiomics Information with Clinical Outcomes for Lung SBRT. Disclosure. Acknowledgements
Correlting Rdiomics Informtion with Clinicl Outcomes for Lung SBRT Fng-Fng Yin, PhD Duke University Medicl Center AAPM 2017 Denver CO Disclosure This reserch is prtilly funded by reserch grnt from Vrin
More informationCorrelations Between Cytogenetic and Molecular Monitoring Among Patients With Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase
Originl Articles Correltions Between Cytogenetic nd Moleculr Monitoring Among Ptients With Newly Dignosed Chronic Myeloid Leukemi in Chronic Phse Post Hoc Anlyses of the Rtionle nd Insight for Gleevec
More informationEffects of 6-Month Sitagliptin Treatment on Insulin and Glucagon Responses in Korean Patients with Type 2 Diabetes Mellitus
Originl Article Others Dibetes Metb J 215;39:335-341 http://dx.doi.org/1.493/dmj.215.39.4.335 pissn 2233-679 eissn 2233-687 DIABETES & METABOLISM JOURNAL Effects of 6-Month Sitgliptin Tretment on Insulin
More informationSeasonal influenza vaccination programme country profile: Ireland
Sesonl influenz vccintion progrmme country profile: Irelnd 2012 13 Seson Bckground informtion Influenz immunistion policy nd generl fcts bout Irelnd Volume indices of GDP per cpit in 2011 nd 2013 (EU-
More information