PRIKAZ SLUČAJA: BOLESNICA S PROTEINURIJUM NEPOZNATE ETIOLOGIJE?

PRIKAZ SLUČAJA:

BOLESNICA S PROTEINURIJUM NEPOZNATE ETIOLOGIJE?

Dr. sc. D. MATIŠIĆ Doc. dr. sc. B. JELAKOVIĆ

Dr. sc. M. LAGANOVIĆ

Djetinjstvo:

- vodene kozice, - uroinfekti, - negira enurezu

12.2.2008. Ambulanta za hipertenziju i nefrologiju – nefrotska proteinurija za koju zna unazad 5 godina (?).

Dolazi u pratnji supruga.

S.P., 1976. Zagreb, udana, majka 2 djece, profesorica u osnovnoj školi

Iz anamneze:

1999. operacija lijeve dojke – karcinom, zračena 5 ciklusa, bez kemoterapije

2001. ugrađen silikonski implantat, ostavljene mliječne žlijezde trudnoća - spontani pobačaj u 16-om tjednu

2002. trudnoća -spontani pobačaj u 18-om tjednu - tlak normalan, bez edema, - nema podataka o proteinuriju, - uroinfekt

2003. trudnoća – koncem trudnoće hipertenzija, proteinurija 3 gr porod carskim rezom, dijete teško 3100 gr - nema daljnjih kontrola (?)

2005. trudnoća - proteinurija 14 - 9,1 gr. Sumnja na HELLP sindrom – otklonjena. Liječena u Intenzivnoj jedinici u KB Sestre milosrdnice - proteinurija 0 gr (u 2 navrata) porod carskim rezom, dijete teško 2900 gr


Bolesnica dolazi:

u visokom stupnju trudnoće 24. 02. 2005. s proteinurijom od 9,1 g/dU –

ukupni proteini određeni BIURET reagensom

1.jut.urin: relativ. volumna masa: 1,025; pH=5,0; proteini 1,0 g/l; bakterije: 1+Klirens kreatinina korig: 0,746 ml/s (ref.raspon: 1,3-2,1) V= 1340 mlukupni proteini u serumu: 56,0 g/l

α-2-makroglobulin < 0,05 g/l

α-1-mikroglobulin < 5,22 mg/l

α-1-kiseli glikoprotein < 0,05 g/l

IgG < 3,38 mg/l

ß-2-mikroglobulin < 0,21 mg/l

Bjp-kvantitativno (κ i λ) 0,0

Albumin -nefelometrija 2,39 mg/l

28. 02. 2005. proteinurija: 13.26 g/dU – biuret V= 1020 mlukupni proteini u serumu: 58,0 g/l

Klirens kreatinina korig.: 0,352 ml/s (r.f. 1,3-2,1)

Elektroforeza proteina u urinu – fiziološka proteinurija

α-2-makroglobulin < 0,05 g/l

α-1-mikroglobulin < 5,22 mg/l

α-1-kiseli glikoprotein < 0,05 g/l

IgG < 3,38 mg/l

ß-2-mikroglobulin 0,28 mg/l

Bjp-kvantitativno (κ i λ) 0,0

Albumin -nefelometrija 3,87 mg/l

02. 03. 2005. - 2. JUTARNJI URIN

SDS PAGE –

slika ove elektroforeze pokazuje da urin (linija 8)

sadrži više različitih proteina,

a najviše su zastupljeni

albumin i proteini

molekulske mase oko 40 kDa

43 kDa40 kDa

Gel-kromatogram pokazuje više pikova od kojih je najjači onaj na mjestu izlaska albumina.

Vrhovi pikova su analizirani i imunoelektroforezom ali nisu dobivene vidljive precipitacije –najvjerojatnije zbog razrijeđenosti urina??????

Gelkromatografija na Sephacryl S-300

Imunoelektroforeza prema:

anti humanom serumu (AHS), anti humanom albuminu (anti Alb) i anti IgG, A, M (AH-IgG,A,M

Rezultati pokazuju da urin sadrži albumin i tragove IgG.

2005. hipotireoza – koloidna struma, citološka punkcija, uvedena th Euthyrox.

2006. -prometna nesreća – fraktura desne ruke (radii loco tipico) bez udarca u trbuh, bez hematurije - nastanak Sudeckove atrofije, preporučena artrodeza

-trudnoća – spontani pobačaj u 9-om tjednu, proteinurija 4 gr skraćen PV u jednom nalazu

-fibrozna reakcija na slikonski implantat – zamijenjen, uklonjene i mliječne žlijezde

2007. - trudnoća – spontani pobačaj u 2-om tjednu trudnoće, proteinurija 4 gr

Euthyrox povišen na 50 ug – iatrogena hipertireoza (?) UZV vrata – koloidna struma, protutijela negativna

2008. uroinfekt, proteinurija 5,8 gr


Nakon nekog vremena bolesnica se vraća i obrada se ponavlja 2006.:

Biokemija Kompletna pretraga urina Hematologija

Bilirubin 9,5 umol/l Rel.vol.masa 1,025 Eritrocit 3,92

Ureja 2,8 mmol/l pH 5,0 Hemoglobin 123

Kreatinin 82 umol/l Proteini 2+ HCT 0,364

Kreatinin u mokraći 3,52mmol/ 24h Nitriti 1+ MCV 93,0

Klirens kreatinina 0,5 ml/s Eritrociti(hemoglob.) 3+ Trombociti 207

Kalij-serum 4,0 mmol/l Sediment: eritrociti 100 Leukociti 8,41

Natrij 140 mmol/l Bakterije 1+ Neutrofili 72,3

AST 29 U/L Limfociti 1,85

ALT 28 U/L Koagulacija Monociti 0,328

GGT 17 U/L APTV 29 s Eosinofili 0,35

ALP 44 U/L PV 111 %

Basofili 0,117

Proteini-serum 59 g/l Fibrinogen 2,8 g/l

CRP 2,5 mg/l

Proteini u urinu 9,6 g/24 h

V 24h urin 1260 ml

Ista obrada ponavlja se 2007. i slažu se samo novi upitnici:

Biokemija Kompletna pretraga urina

Ureja-serum 2,5 mmol/l Rel.vol.masa 1,025

Ureja-urin 155 mmol/l pH 7,0

Kreatinin 56 umol/l Proteini 3+

Kreatinin u mokraći

4,5mmol/ 24h Nitriti neg

Klirens kreatinina 0,9 ml/s Eritrociti(hemoglob.) Neg

Kalcij 2,65 mmol/l Sediment: eritrociti 1

Fosfati 1,01 mmol/l Bakterije 1+

AST 29 U/L 24 satni urin

ALT 28 U/L Albumin - nefelometrijski < 3,0 mg/l

GGT 17 U/L IgG < 4,1 mg/l

ALP 44 U/L Alfa-1-mikroglobulin < 5,18 mg/l

Proteini-serum 49 g/l Transferin < 0,1 g/l

CRP 2,5 mg/l BJP kvantitativno -kapa 0,00 mg/l

Proteini u urinu 2,39 g/dU BJP kvantitativno -lambda 0,00 mg/l

V 24h urin 1520 ml

Nalaz elektroforeze u 24satnoj mokraći smo na kraju opisali:

Nađena miješana proteinurija koju ne možemo dokazati ni isključiti -

prisutne proteine nije moguće identificirati imunokemijskim

metodama

Proteini u urinu-

pirogalol – 2,39 g / 24 h

Albumin

Uzorak naše bolesnice

ß2m

Navike:

Mokrenje – mutnija, pjenušava; stolica - mekše konzistencije;

Menstruacije –obilne, redovite, OC ne troši (očito)

Apetit nakon 4-og pobačaja loš, ali se udebljala 20-tak kg, sada opet smršavila 20-tak kg uz dijetu.

Puši 5 cigareta dnevno

Od lijekova analgetici (Pentazocin, Analgin), gabapentin

Alergije negira.

U obitelji:

Nije bilo bubrežnih bolesnika.

Baka karcinom dojke, teta karcinom maternice, druga teta karcinom pluća

Ujak karcinom gušterače.


Mlada žena (32 godine) s nefrotskom proteinurijom,normalnom glomerularnom filtracijom (normalan serumski kreatinin)normotenzivna

Operiran karcinom dojke (zračena, bez kemoth.)Kontrolirana hipotireoza (koloidna struma)Učestali spontani pobačaji (4x)U jednoj trudnoći hipertenzija, proteinurija (eklampsija ?)

Nefrotski sindrom – potrebna hospitalna obrada

Bubrežna bolest u sklopu :

sistemske bolesti (antifosfolipidni sy.) ?karcinom dojke – paraneoplastički ?silikonski implantati ?bolest štitnjače ?nesteroidni antireumatici ?


+ nejasan nalaz proteinurije

1. Karcinom dojke:

Breast cancer with nephrotic syndrome: report of two cases.Kijima et al. Surg Today. 2004;34(9):755-9

To our knowledge, there are only four other reported cases of paraneoplastic membranous nephropathy complicating breast cancer.

Paraneoplastic nephrotic syndrome in advanced breast cancer patient. A case report.

Valcamonico et al.Tumori. 2004 Jan-Feb;90(1):154-6.

A case of paraneoplastic nephrotic syndrome (NS) is described five years after the diagnosis of breast cancer.

Nephrotic syndrome associated with adenocarcinoma of the breast.Barton et al.Am J Med. 1980 Feb;68(2):308-12

The findings on renal biopsy were indicative of membranous nephropathy with positive immunofluorescent staining for immunoglobulin G (IgG) and the third component of complement (C3).

Primary amyloidosis of the breast associated with invasive breast cancer.

White et al.Oncol Rep. 2004 Apr;11(4):761-3.

A localised form can involve the breast and may mimic breast cancer. We report a case of primary amyloid deposit confirmed by immunohistochemistry, occurring in a patient with early breast cancer

Henoch-Schönlein syndrome associated with breast cancer. A case report.

Maestri et al. Angiology. 1995 Jul;46(7):625-7

The authors report a case of malignant breast tumor wherein cutaneous vasculitis appeared at the moment of the disease's progression

1. Karcinom dojke:

2. Silikonski implantati:

Multiple autoantibodies in patients with silicone breast implants.

Bar-Meir et al. J Autoimmun. 1995 Apr;8(2):267-77

All 250 sera were tested blindly using a panel of 20 autoantigens including SS-A, SS-B, RNP, cardiolipin (CL), collagen types I, II and IV, phosphatidylserine (PS), myeloperoxidase (MPO), sulfatides (sulf), thyroglobulin (TG), gangliosides (GDIa;GM2), proteinase-3 (PR3), Jo-1, Sm, HPRPP-ribosomal phosphate, histones (H2AH2B), Scl-70 and glomerular basement membrane (NC-1). There was a statistically significant greater

frequency of autoantibodies in women with implants

Association of silicone breast implants with immunologic abnormalities: a prospective study.

Karlson et al Am J Med. 1999 Jan;106(1):11-9

We found no increased frequency of any immunologic abnormalities in women exposed to silicone breast implants, except for anti-ssDNA, which has unknown clinical relevance


Silicone breast implants and the risk of connective-tissue diseases and symptoms.

Sanchez-Guerrero et al N Engl J Med. 1995 Jun 22;332(25):1666-70

In a large cohort study, we did not find an association between silicone breast implants and connective-tissue diseases, defined according to a variety of standardized criteria, or signs and symptoms of these diseases.

Autoimmune reactions in patients with silicone breast implants.

Zazgornik et al. Wien Klin Wochenschr. 1996 Dec 27;108(24):773-4.

none of the investigated women with silicone breast implants showed clinical symptoms or signs of connective tissue disease according to ARA criteria.

Do silicone breast implants cause rheumatologic disorders? A systematic review for a court-appointed national science panel.

Tugwell et al Arthritis Rheum. 2001 Nov;44(11):2477-84

The panel found no evidence to support expert testimony suggesting an association between silicone breast implants and connective diseases.


Meta-analyses of the relation between silicone breast implants and the risk of connective-tissue diseases.

Janowsky et al.N Engl J Med. 2000 Mar 16;342(11):781-90

There was no evidence of an association between breast implants in general, or silicone-gel-filled breast implants specifically, and any of the individual connective-tissue diseases, all definite connective-tissue diseases combined, or other autoimmune or rheumatic conditions

The association between silicone implants and both antibodies and autoimmune diseases.

Bekercioglu et al.Clin Rheumatol. 2008 Feb;27(2):147-50.

In conclusion, silicone materials do lead to an immune response consisting of antisilicone antibodies most evident immediately adjacent to the implant itself.

3. Štitnjača:

Autoimmune thyroiditis with associated proteinuria: report of two patients.

Agras et al J Pediatr Endocrinol Metab. 2005 Mar;18(3):319-22

Renal findings associated with autoimmune thyroiditis present more commonly as proteinuria ranging from mild to nephrotic levels

Proteinuria in autoimmune thyroid disease.

Proteinuria was found in 29.8% of patients with autoimmune thyroid disease and in 9.5% of patients attending the same clinic but without these conditions.

Weetman et al Acta Endocrinol (Copenh). 1985 Jul;109(3):341-7.

Thyroid antigen-mediated glomerulonephritis in Graves' disease.

Sato et al.Clin Nephrol. 1989 Jan;31(1):49-52.

Immune complex glomerulonephritis mediated by thyroid antigens.

Jordan et al Arch Pathol Lab Med. 1978 Oct;102(10):530-3.

These observations suggest development of immune complex glomerulonephritis mediated by thyroid antigens.

9.3.2008. hospitalizirana u Zavodu za nefrologiju i arterijsku hipertenziju

Iz statusa:

-oskudnije koštane i mišićne građe, TT 54 kg TV 168 cm ITM 20

-anikterična, eupnoična, uredno prokrvljenih sluznica, uredna izgleda kože

-slikinonski implantati, postoperativni ožiljci

-štitnjača nije palpatorno uvećana

-srce i pluća uredni RR 125/75 mmHg c=70/min

-trbuh uredan

-nema edema, Sudeckova atrofija desne šake i podlaktice


Iz nalaza:

SE 11 E 3,47 Hb 110 Hct 0,32 MCV 93,1 L 6,9 Tr 227PV 0,88-1,03 APTV 59,9-26,5-24,7 (N do 33) fibrinogen 2,2 lupus antikoagulant neg

urin: proteini – ; 2+; 4+; -;4+ E 0-2; masaurinokultura sterilna

GUK 3,9 urea 2,6 kreatinin 58-59 ac.uricum 310 AF 13 AST/ALT 13/7 gamaGT 19K 3,7-3,4-3,5 Na 144-133-142 Cl 105 Ca 2,35 P 1,39

Fe 6 UIBC 39 TIBC 45 feritin 85,7

Ukupni proteini 54 (34,5-2,5-5,6-5,3-6,0)IgA 1,35 IgG 5,59 (N 7,0-16,0) IgM 0,88Imunofiksacija – hipogamaglobulinemija

Transferin 1,98; beta2 mikrog 1,18; haptoglobin 1,47; ceruloplazmin 0,3


Tumorski biljezi:Cu 15,5

CA 15-3 8,2 (N<25)AFP 1,63 (N<13,4)CA 125 14,0 (N<35)CA 19-9 4,6 (N<37)

Endokrinološki:LH 7 (N za ovulacijsku fazu)FSH 4 - II -Prolaktin 8Testosteron 0,9Kortizol 248 Beta HCG < 0,10

TSH < 0,05 FT3 7,3 FT4 19,5Imunološki:ANA (ENA) negANCA PR3 1ANCA MPO 1Hu, Yo, Ri negaCl IgG 3aCl IgM 6AGBM negRF 10,8Komplement – norm; C3 0,73 (N 0,9-1,8) C4 0,31

CRP 3,1-5,4-1,1

Markeri hepatitisa:

HBsAg negAnti HBs pozitivan > 500Anti HBc pozitivan > 0,10Anti HBc IgM negativanAnti HBe 0,00Anti HCV negativan


Rtg srca i pluća – uredan nalaz; okruglaste sjene u području obje dojke odgovaraju implantatima

UZV bubrega – uredne veličine i debljine parenhima uredne ehogenosti

MSCT dojki - u obje aksile l.č. do 14,6 mm - desna dojka uredan implantat i žljezdano tkivo - lijeva dojka veća, bliže medijalno i prema sternumu, nepravilno oblikovana meka tkiva, promjene otvorene etiologije ?!

Neurolog – uredan nalaz


24h proteinurija kod dolaska na odjel: 8,4 – 15 – 4,3 gr/dU

20.3.2008. biopsija bubrega

Svjetlosna mikroskopija:2 cilindra, 36 glomerula3 sklerozirana33 mjestimice proširen mezangijU intersticiju se ne vidi patoloških promjenaU arterijama nema patoloških promjenaNa kanalićima se ne vidi patoloških promjena

Imunoflorescencija:Svi serumi su negativni osim IgM u tragovima u mezangijuSrednje obilni C3 i fibrin u stjenkama krvnih žila

Zaključak patologa:U ovom materijali osim mjestimice proširenog mezangija u glomerulima ne vidi se drugih patološih promjena.


Nakon biopsije – hematom bubrega - mirovanje

24h proteinurija - 0,12 g/dU

Postavljen urinarni kateter


24h proteinurija kod dolaska na odjel: 8,4 – 15 – 4,3 gr/dU

24h proteinurija – 0,08 g/dU

proteinuira

0

2

4

68

10

12

14

16

14.2.05

24.2.05

28.2.05

2.3.05

4.3.05

14.6.06

3.7.06

4.12.07

5.12.07

5.2.08

6.2.08

7.2.08

11.2.08

19.2.08

10.3.08

11.3.08

13.3.08

14.3.08

19.3.08

20.3.08

21.3.08

date

g/d

U

rodilište intenzivna

Prijem u V.int

V.int

kateter

Amb


proteinuira & albuminuria

02468

10121416

14.2.

05

28.2.

05

4.3.

05

3.7.

06

5.12

.07

6.2.

08

11.2.

08

10.3.

08

13.3.

08

19.3.

08

21.3.

08

date

g/d

U

g/m

l

proteinuria albuminuria


mixtneselct neselct

mixt select

Uzorak br.1. : proteinurija 0,5g/l

Uzorak br.1 + otop. belanjak

Otopina čistog bjelanjka

Uzorak naše bolesnice

ß2m

Albumin

Linija 10,11,12-serumi pileta

HPLC- kromatogram je sličan onom dobivenom sa Sephacryl-a S-300. Prema ovom nalazu urin sadrži i neki protein manji od albumina skoro u istoj količini kao i albumin

total prot&albumin

01020304050607080

14.2.05

28.2.05

4.3.05

3.7.06

5.12.07

6.2.08

11.2.08

10.3.08

13.3.08

19.3.08

21.3.08

date

g/l

total protein albumin

N

N



datumc-creatinine

umol/lu-creatinine

umol/lu- volume

mlclearenc

e ml/sclearence

ml/min MDRD4 C-Gproteinuria

g/dU

14.2.05. 52 2470 975 0,55 33 127,1 134,2 4,87

24.2.05. 56 3609 1340 0,74 44,4 116,6 124,6 9,1

28.2.05. 59 1765 1020 0,35 21 109,8 118,3 13,26

6.7.06. 82 2793 1260 0,5 30 74,6 84,3 9,6

4.12.07. 56 2960 1520 0,9 54 115,1 122,4 1,57

7.2.08. 79 1590 880 0,29 17,4 77,8 85,9 5,8

11.3.08. 64 2000 99,2 100,1 8,4

13.3.08. 59 2526 1900 1,35 81 109 110 4,3

21.3.08. 58 8500 1000 2,44 146,4 111,2 118,2 0,12

Nema dokumentacije o operativnom zahvatu dojki ???

– pitanje estetike ili ?

Namjerno izazvana “hipotireoza” (samo TSH trajno snižen) ?

Psihijatar:

Niz traumatskih i stresnih događaja tijekom života.Teško podnosi odvojenost od djece, zabrinuta i glede zdravstvenih poteškoćaIz psihičkog profila:prisvjesna, orijentirana, urednog kontakta bez pishotičnih sadržajaNegira suicidalne ideje, nije heteroagresivna.Suradljiva, dobrog uvida u svoje stanje.Dg F43.2 (Poremećaj prilagodbe: PTSP, mobing)Preporuča se psihoterapijski tretman.


Egzogeni protein namjerno dodavan u mokraću

Münchausen Sy.

Ireland i ostali – 8 kriterija:

1. dramatska prezentacija bolesti 2. lažiranje dokumentacije o bolesti 3. višestruke medicinske intervencije 4. patološka lažljivost 5. agresivno ponašanje 6. napuštanje bolnice/dg. ili th. postupka unatoč savjetu 7. višestruke hospitalizacije na raznim lokacijama 8. nema podatka o postizanju neke koristi

-prvi puta opisan 1951. godine (Asher)

√ √ √ √ √

√

√

[Three cases of Munchausen's syndrome mimicking connective tissue diseases]

Tacahashi et al .Ryumachi. 1998 Aug;38(4):618-22

The patients with Munchausen syndrome sometimes show various symptoms and signs of multisystem inflammatory diseases, which mimick the clinical feature of connective tissue diseases

Urological aspects of Munchausen's syndrome.

Heimbach et al. Eur Urol. 1997;31(3):371-5

In urology, the 'hemorrhagic type', the 'abdominal type' and the 'neurological type' are predominant.

[The Munchausen syndrome: a diagnosis not to be forgotten in urology]

Nephritic colitis, false gall stones, addition of fecal matter or of food and saliva in the urine or the bladder, neurogenic bladder and urinary infections have all been reported as possible manifestations of Münchausen's syndrome.

Hermieu et al Presse Med. 2002 Jan 26;31(3):119-21

Munchausen's syndrome and prophylactic mastectomy.

Grenga et al Plast Reconstr Surg. 1987 Jul;80(1):119-20.

A patient sought bilateral prophylactic mastectomies because of a strongly positive family history of breast cancer.

Nephrectomy and solitary kidney biopsy in a patient with Munchausen's syndrome.

Schmist et al. Nephrol Dial Transplant. 1996 May;11(5):890-2

Munchausen's syndrome and the laboratory. Self-injection of human chorionic gonadotropin.

Schwartz et al. Arch Pathol Lab Med. 1995 Jan;119(1):85-8

Although the patient's sonogram was negative for an intrauterine pregnancy, an ectopic pregnancy could not be ruled out and the patient was taken to surgery…

… medical history revealed that she had 30 previous surgical procedures,

Exogenous protein as the cause of nephrotic-range proteinuria.

Mitas, Am J Med. 1985 Jul;79(1):115-8

Quantitatively, the proteinuria was in the nephrotic range, but other manifestations of the nephrotic syndrome were absent.

Urine protein electrophoresis confirmed severe proteinuria with a spike in the gamma region.

Factitious proteinuria in a young girl.

Tojo et al. Clin Nephrol. 1990 Jun;33(6):299-302.

It appears that the proteinuria was factitious and that egg proteins were injected into the bladder, as they were also present in the bladder urine.

Electrophoresis of the urinary protein showed two abnormal fractions at the alpha and beta globulins. Immunoelectrophoresis demonstrated that these abnormal proteins were not derived from human serum proteins,

Factitious proteinuria: diagnosis and protein identification by use of isoelectric focusing.

Sutcliffe et al Clin Chem. 1988 Aug;34(8):1653-5.

By isoelectric focusing we identified it as egg-white, a finding confirmed by immunofixation with antiserum to egg-albumen.

urine creatinine umol/l

0

1000

2000

3000

4000

5000

6000

7000

8000

9000

1 2 3 4 5 6 7 8 9

urine volume ml

0

500

1000

1500

2000

2500

1 2 3 4 5 6 7 8 9

Glomerular filtration

020406080

100120140160

1 2 3 4 5 6 7 8 9

date

ml/m

in

creatinine clearence MDRD 4 C-G formula

proteinurija g/dU

0

2

4

6

8

10

12

14

1 2 3 4 5 6 7 8 9

g/dU

S.P., 1976. ZagrebSutcliffe et al Clin Chem. 1988

Serial factitious disorder and Munchausen by proxy in pregnancy.

Thabuy et al Rev Med Interne. 2008 Nov;29(11):924-8

We report on a 44-year-old woman who, over a period of two decades, self-induced labour and delivery in five consecutive pregnancies

She precipitated labour by rupturing her own amniotic sac with a fingernail or cervical manipulation, or misappropriating and self-administering prostaglandin suppositories

Munchausen's syndrome: a medico-legal dilemma.

Mydlo et al Med Sci Law. 1997 Jul;37(3):198-201

In his or her life-long career, the physician will eventually encounter a patient with factitious disorder, or Munchausen's syndrome.

SVE NAJBOLJE ZA NADOLAZEĆE BLAGDANE,

ZDRAVLJA I SREĆE

A sve ostalo već nekak bu !

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PRIKAZ SLUČAJA: BOLESNICA S PROTEINURIJUM NEPOZNATE ETIOLOGIJE?