PRIKAZ SLUAJA BOLESNICA S PROTEINURIJUM NEPOZNATE ETIOLOGIJE Dr

PRIKAZ SLUČAJA: BOLESNICA S PROTEINURIJUM NEPOZNATE ETIOLOGIJE? Dr. sc. D. MATIŠIĆ Doc. dr. sc. B. JELAKOVIĆ Dr. sc. M. LAGANOVIĆ

S. P. , 1976. Zagreb, udana, majka 2 djece, profesorica u osnovnoj školi 12. 2. 2008. Ambulanta za hipertenziju i nefrologiju – nefrotska proteinurija za koju zna unazad 5 godina (? ). Dolazi u pratnji supruga. Djetinjstvo: - vodene kozice, - uroinfekti, - negira enurezu

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/d. U – ukupni proteini određeni BIURET reagensom 1. jut. urin: relativ. volumna masa: 1, 025; p. H=5, 0; proteini 1, 0 g/l; bakterije: 1+ Klirens kreatinina korig: 0, 746 ml/s (ref. raspon: 1, 3 -2, 1) V= 1340 ml ukupni proteini u serumu: 56, 0 g/l 28. 02. 2005. proteinurija: 13. 26 g/d. U – biuret V= 1020 ml ukupni 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 02. 03. 2005. - 2. JUTARNJI URIN α-2 -makroglobulin < 0, 05 g/l α-1 -mikroglobulin < 5, 22 mg/l α-1 -kiseli glikoprotein < 0, 05 g/l Ig. G < 3, 38 mg/l ß-2 -mikroglobulin < 0, 21 mg/l ß-2 -mikroglobulin 0, 28 mg/l Bjp-kvantitativno (κ i λ) 0, 0 Albumin -nefelometrija 2, 39 mg/l Albumin -nefelometrija 3, 87 mg/l

SDS PAGE – slika ove elektroforeze pokazuje da urin (linija 8) sadrži više različitih proteina, a najviše su zastupljeni 40 k. Da 43 k. Da albumin i proteini molekulske mase oko 40 k. Da

Gelkromatografija na Sephacryl S-300 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? ? ?

Imunoelektroforeza prema: anti humanom serumu (AHS), anti humanom albuminu (anti Alb) i anti Ig. G, A, M (AH-Ig. G, A, M Rezultati pokazuju da urin sadrži albumin i tragove Ig. G.

S. P. , 1976. Zagreb, udana, majka 2 djece, profesorica u osnovnoj školi 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 p. H 5, 0 Hemoglobin 123 Kreatinin 82 umol/l Proteini 2+ HCT 0, 364 Kreatinin u mokraći 3, 52 mmol/ 24 h Nitriti 1+ MCV 93, 0 Klirens kreatinina 0, 5 ml/s Eritrociti(hemoglob. ) 3+ Trombociti 207 Kalij-serum 4, 0 mmol/l Sediment: eritrociti Ø 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 24 h urin 1260 ml

Ista obrada ponavlja se 2007. i slažu se samo novi upitnici: Biokemija Kompletna pretraga urina Proteini u urinu- Ureja-serum 2, 5 mmol/l Rel. vol. masa 1, 025 Ureja-urin 155 mmol/l p. H 7, 0 Kreatinin 56 umol/l Proteini 3+ Kreatinin u mokraći 4, 5 mmol/ 24 h 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 Ig. G < 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/d. U BJP kvantitativno -lambda 0, 00 mg/l V 24 h urin 1520 ml pirogalol – 2, 39 g / 24 h ß 2 m Albumin Uzorak naše bolesnice Nalaz elektroforeze u 24 satnoj mokraći smo na kraju opisali: Nađena miješana proteinurija koju ne možemo dokazati ni isključiti prisutne proteine nije moguće identificirati imunokemijskim metodama

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

S. P. , 1976. Zagreb, udana, majka 2 djece, profesorica u osnovnoj školi 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 (4 x) 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 (Ig. G) and the third component of complement (C 3).

1. Karcinom dojke: 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

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; GM 2), proteinase-3 (PR 3), Jo-1, Sm, HPRPP-ri bosomal phosphate, histones (H 2 AH 2 B), Scl-70 and There was a statistically glomerular basement membrane (NC-1). 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-ss. DNA, which has unknown clinical relevance

2. Silikonski implantati: 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.

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

S. P. , 1976. Zagreb, udana, majka 2 djece, profesorica u osnovnoj školi 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 mm. Hg c=70/min -trbuh uredan -nema edema, Sudeckova atrofija desne šake i podlaktice

S. P. , 1976. Zagreb, udana, majka 2 djece, profesorica u osnovnoj školi Iz nalaza: SE 11 E 3, 47 Hb 110 Hct 0, 32 MCV 93, 1 L 6, 9 Tr 227 PV 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; masa urinokultura sterilna GUK 3, 9 urea 2, 6 kreatinin 58 -59 ac. uricum 310 AF 13 AST/ALT 13/7 gama. GT 19 K 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) Ig. A 1, 35 Ig. G 5, 59 (N 7, 0 -16, 0) Ig. M 0, 88 Imunofiksacija – hipogamaglobulinemija Transferin 1, 98; beta 2 mikrog 1, 18; haptoglobin 1, 47; ceruloplazmin 0, 3

S. P. , 1976. Zagreb, udana, majka 2 djece, profesorica u osnovnoj školi 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 8 Testosteron 0, 9 Kortizol 248 Beta HCG < 0, 10 TSH < 0, 05 FT 3 7, 3 FT 4 19, 5 Imunološki: ANA (ENA) neg ANCA PR 3 1 Markeri hepatitisa: ANCA MPO 1 Hu, Yo, Ri neg HBs. Ag neg a. Cl Ig. G 3 Anti HBs pozitivan > 500 a. Cl Ig. M 6 Anti HBc pozitivan > 0, 10 AGBM neg Anti HBc Ig. M negativan RF 10, 8 Anti HBe 0, 00 Komplement – norm; C 3 0, 73 (N 0, 9 -1, 8) C 4 0, 31 Anti HCV negativan CRP 3, 1 -5, 4 -1, 1

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

S. P. , 1976. Zagreb, udana, majka 2 djece, profesorica u osnovnoj školi 24 h proteinurija kod dolaska na odjel: 8, 4 – 15 – 4, 3 gr/d. U 20. 3. 2008. biopsija bubrega Svjetlosna mikroskopija: 2 cilindra, 36 glomerula 3 sklerozirana 33 mjestimice proširen mezangij U intersticiju se ne vidi patoloških promjena U arterijama nema patoloških promjena Na kanalićima se ne vidi patoloških promjena Imunoflorescencija: Svi serumi su negativni osim Ig. M u tragovima u mezangiju Srednje obilni C 3 i fibrin u stjenkama krvnih žila Zaključak patologa: U ovom materijali osim mjestimice proširenog mezangija u glomerulima ne vidi se drugih patološih promjena.

S. P. , 1976. Zagreb, udana, majka 2 djece, profesorica u osnovnoj školi 24 h proteinurija kod dolaska na odjel: 8, 4 – 15 – 4, 3 gr/d. U Nakon biopsije – hematom bubrega - mirovanje 24 h proteinurija - 0, 12 g/d. U Postavljen urinarni kateter 24 h proteinurija – 0, 08 g/d. U

S. P. , 1976. Zagreb, udana, majka 2 djece, profesorica u osnovnoj školi Amb Prijem u V. int rodilište intenzivna V. int kateter

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

ß 2 m Albumin Uzorak br. 1. : proteinurija 0, 5 g/l Uzorak br. 1 + otop. belanjak Otopina čistog bjelanjka Uzorak naše bolesnice 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

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

S. P. , 1976. Zagreb, udana, majka 2 djece, profesorica u osnovnoj školi c-creatinine umol/l u- volume ml clearence ml/s clearence ml/min MDRD 4 C-G proteinuria g/d. U 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 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 datum 2000

S. P. , 1976. Zagreb, udana, majka 2 djece, profesorica u osnovnoj školi Egzogeni protein namjerno dodavan u mokraću 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 poteškoća Iz psihičkog profila: prisvjesna, orijentirana, urednog kontakta bez pishotičnih sadržaja Negira suicidalne ideje, nije heteroagresivna. Suradljiva, dobrog uvida u svoje stanje. Dg F 43. 2 (Poremećaj prilagodbe: PTSP, mobing) Preporuča se psihoterapijski tretman.

Münchausen Sy. -prvi puta opisan 1951. godine (Asher) 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 √

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

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. 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, 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.

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.

Sutcliffe et al Clin Chem. 1988 S. P. , 1976. Zagreb

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 !