Scrotal mass differential diagnosis: Difference between revisions
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{{CMG}};{{AE}}{{Preeti}} | {{CMG}};{{AE}}{{Preeti}} | ||
==Overview== | ==Overview== | ||
*The table below summarizes the findings that differentiates scrotal mass according to the clinical features, laboratory findings, imaging features, histological features, and genetic studies. | *The table below summarizes the findings that differentiates scrotal mass according to the clinical features, laboratory findings, imaging features, histological features, and genetic studies. |
Revision as of 20:34, 18 October 2019
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Preeti Singh, M.B.B.S.[2]
Overview
- The table below summarizes the findings that differentiates scrotal mass according to the clinical features, laboratory findings, imaging features, histological features, and genetic studies.
Diseases | Clinical manifestations | Para-clinical findings | Gold standard | Associated | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Symptoms | Physical examination | ||||||||||||||
Lab Findings | Past Medical History | Histopathology | |||||||||||||
Unilateral /Bilateral swelling | Onset | Fever | Urinary symptoms | Tender -ness |
Erythema | Discharge | Inguinal Lymphadenopathy | Cremasteric Reflex | Blood/Urine Analysis | Doppler U/S | |||||
Painful | |||||||||||||||
Epididymitis[1][2] [3][4][5][6][7][8] |
Unilateral | Gradual | ± | Dysuria, frequency, and/or urgency | + | - | +
(Pyuria Bacteriuria) |
Painful local lymphadenopathy | + |
|
|
|
|
|
|
Orchitis | Bilateral | Abrupt | ± | Dysuria | + | - | ± | Painful local lymphadenopathy | + |
|
|
|
|
|
|
Testicular Torsion[15][16][17][18][19][7] | Unilateral | Sudden | - | Absent | + | + | +
Blood in semen may be present |
Absent | - |
|
|
|
|
| |
Hematocele[20][21] [22][23][24] |
Unilateral or bilateral | Sudden | - | Absent | + | + | +
Blood in semen |
Absent | - |
|
Scrotal wall thickening and testicular hematoma | Testicular trauma related to:
|
|
|
_ |
Incarcerated Hernia[25][26] | Unilateral | Sudden | + | Absent | + | + | - | Absent | + |
|
|
- | - |
|
|
Brucellosis[27][28][29][30] | Unilateral or Bilateral | Sudden | ± | Dysuria | - | - | ± | Painful local lymphadenopathy | + |
|
|
- |
|
|
Antibodies are detected using:
|
Torsion of the appendix testis[31][32][33][34] | Unilateral or Bilateral | Sudden | - | Absent | + | - | - | Absent | + |
|
|
- |
|
|
|
Henoch-Schonlein purpura[35][36][37][38] | Unilateral | Sudden | - | Absent | + | + | - | - | - |
|
- |
|
|
Biopsy |
|
Fournier's gangrene[39][40][41][42] | Bilateral | Sudden | + | Absent | + | + | - | - | + |
|
- | - | - |
|
|
Diseases | Unilateral /Bilateral swelling | Onset | Fever | Urinary symptoms | Tender<be>-ness | Erythema | Discharge | Inguinal Lymphadenopathy | Cremasteric Reflex | Blood/Urine Analysis | Doppler U/S | Past Medical History | Histopathology | Gold standard | Additional findings |
Painless | |||||||||||||||
Fragile X Macroorchidism[43][44][45][46] | Bilateral | Gradual | - | Absent | - | - | + | Absent | + |
|
- | - | Increased volume of testis |
|
|
Testicular Tumors[47][48][49][50] | Unilateral or bilateral | Gradual | ± | Absent | ± | + | Present | + |
|
- | - | Seminoma shows findings such as:
|
|
| |
Hydrocele[51][52][53][54][55] | Bilateral | Gradual | - | Absent | - | - | - | Absent | + | - |
|
- | - |
|
|
Varicocele[56][57][58][59] | Unilateral
(Mainly left) |
Gradual | Local warmth | Absent | - | ± | - | Absent | + |
|
|
|
- |
|
|
Spermatocele[60][55][61] | Unilateral | Gradual | - | Absent | - | - | - | Absent | + | - |
|
|
|
|
|
Scrotal edema[62][63] | Bilateral and can extend to perineum | Gradual | - | Absent | - | - | - | Absent | + |
|
|
|
- |
|
|
Sebaceous cyst[64][65][66] | Unilateral | Gradual | - | Absent | - | - | - | Absent | + | - |
|
- |
|
|
|
Carcinoma of the scrotum[67][68][69] | - | Gradual | - | Absent | - | - | - | Absent | + | - |
|
- |
|
|
|
Chylocele (Filariasis)[70][71][72] | Unilateral or Bilateral | Gradually
Rapidly |
+ | Absent | - | - | - | Absent | + |
|
|
- | - |
|
|
Scrotoliths[73][74][75] | Unilateral | Gradual | - | Absent | - | - | - | Absent | + | - |
|
|
- |
|
|
References
- ↑ Yu KJ, Wang TM, Chen HW, Wang HH (2012). "The dilemma in the diagnosis of acute scrotum: clinical clues for differentiating between testicular torsion and epididymo-orchitis". Chang Gung Med J. 35 (1): 38–45. PMID 22483426.
- ↑ Manavi K, Turner K, Scott GR, Stewart LH (May 2005). "Audit on the management of epididymo-orchitis by the Department of Urology in Edinburgh". Int J STD AIDS. 16 (5): 386–7. doi:10.1258/0956462053888853. PMID 15949072.
- ↑ Lee YS, Kim SW, Han SW (2018). "Different managements for prepubertal epididymitis based on a preexisting genitourinary anomaly diagnosis". PLoS ONE. 13 (4): e0194761. doi:10.1371/journal.pone.0194761. PMC 5905873. PMID 29668706.
- ↑ Ralls PW, Jensen MC, Lee KP, Mayekawa DS, Johnson MB, Halls JM (June 1990). "Color Doppler sonography in acute epididymitis and orchitis". J Clin Ultrasound. 18 (5): 383–6. PMID 2161009.
- ↑ Michel V, Pilatz A, Hedger MP, Meinhardt A (2015). "Epididymitis: revelations at the convergence of clinical and basic sciences". Asian J. Androl. 17 (5): 756–63. doi:10.4103/1008-682X.155770. PMC 4577585. PMID 26112484.
- ↑ Tracy CR, Costabile RA (April 2009). "The evaluation and treatment of acute epididymitis in a large university based population: are CDC guidelines being followed?". World J Urol. 27 (2): 259–63. doi:10.1007/s00345-008-0338-0. PMID 19002691.
- ↑ 7.0 7.1 7.2 Pepe P, Panella P, Pennisi M, Aragona F (October 2006). "Does color Doppler sonography improve the clinical assessment of patients with acute scrotum?". Eur J Radiol. 60 (1): 120–4. doi:10.1016/j.ejrad.2006.04.016. PMID 16730939.
- ↑ 8.0 8.1 Ludwig M (April 2008). "Diagnosis and therapy of acute prostatitis, epididymitis and orchitis". Andrologia. 40 (2): 76–80. doi:10.1111/j.1439-0272.2007.00823.x. PMID 18336454.
- ↑ Davis NF, McGuire BB, Mahon JA, Smyth AE, O'Malley KJ, Fitzpatrick JM (April 2010). "The increasing incidence of mumps orchitis: a comprehensive review". BJU Int. 105 (8): 1060–5. doi:10.1111/j.1464-410X.2009.09148.x. PMID 20070300.
- ↑ CHARNY CW, MERANZE DR (July 1948). "Pathology of mumps orchitis". J. Urol. 60 (1): 140–6. PMID 18873054.
- ↑ Bjorvatn B (1973). "Mumps virus recovered from testicles by fine-needle aspiration biopsy in cases of mumps orchitis". Scand. J. Infect. Dis. 5 (1): 3–5. PMID 4580293.
- ↑ Beard CM, Benson RC, Kelalis PP, Elveback LR, Kurland LT (January 1977). "The incidence and outcome of mumps orchitis in Rochester, Minnesota, 1935 to 1974". Mayo Clin. Proc. 52 (1): 3–7. PMID 609284.
- ↑ Gall EA (July 1947). "The Histopathology of Acute Mumps Orchitis". Am. J. Pathol. 23 (4): 637–51. PMC 1934294. PMID 19970951.
- ↑ Başekim CC, Kizilkaya E, Pekkafali Z, Baykal KV, Karsli AF (2000). "Mumps epididymo-orchitis: sonography and color Doppler sonographic findings". Abdom Imaging. 25 (3): 322–5. PMID 10823460.
- ↑ Hazeltine M, Panza A, Ellsworth P (2017). "Testicular Torsion: Current Evaluation and Management". Urol Nurs. 37 (2): 61–71, 93. PMID 29240370.
- ↑ Estremadoyro V, Meyrat BJ, Birraux J, Vidal I, Sanchez O (February 2017). "[Diagnosis and management of testicular torsion in children]". Rev Med Suisse (in French). 13 (550): 406–410. PMID 28714632.
- ↑ Sharp VJ, Kieran K, Arlen AM (December 2013). "Testicular torsion: diagnosis, evaluation, and management". Am Fam Physician. 88 (12): 835–40. PMID 24364548.
- ↑ Mikuz G (1985). "Testicular torsion: simple grading for histological evaluation of tissue damage". Appl Pathol. 3 (3): 134–9. PMID 3842075.
- ↑ Gunther P, Schenk JP, Wunsch R, Holland-Cunz S, Kessler U, Troger J, Waag KL (November 2006). "Acute testicular torsion in children: the role of sonography in the diagnostic workup". Eur Radiol. 16 (11): 2527–32. doi:10.1007/s00330-006-0287-1. PMID 16724203.
- ↑ Bowen DK, Gonzalez CM (2014). "Intratesticular hematoma after blunt scrotal trauma: a case series and algorithm-based approach to management". Cent European J Urol. 67 (4): 427–9. doi:10.5173/ceju.2014.04.art24. PMC 4310892. PMID 25667770.
- ↑ Askari R, Khouzam RN, Dishmon DA (2017). "Image Diagnosis: Rapidly Enlarging Scrotal Hematoma: A Complication of Femoral Access?". Perm J. 21. doi:10.7812/TPP/16-111. PMC 5469436. PMID 28609265.
- ↑ Mizutani Y, Miyakawa M (February 1991). "[A case of idiopathic chronic scrotal hematocele]". Hinyokika Kiyo (in Japanese). 37 (2): 199–201. PMID 2048502.
- ↑ Kratzik C, Hainz A, Kuber W, Donner G, Lunglmayr G, Frick J, Schmoller HJ (November 1989). "Has ultrasound influenced the therapy concept of blunt scrotal trauma?". J. Urol. 142 (5): 1243–6. PMID 2681835.
- ↑ Rao MS, Arjun K (October 2012). "Sonography of scrotal trauma". Indian J Radiol Imaging. 22 (4): 293–7. doi:10.4103/0971-3026.111482. PMC 3698892. PMID 23833421.
- ↑ Jenkins JT, O'Dwyer PJ (2008). "Inguinal hernias". BMJ. 336 (7638): 269–72. doi:10.1136/bmj.39450.428275.AD. PMC 2223000. PMID 18244999.
- ↑ Berger D (2016). "Evidence-Based Hernia Treatment in Adults". Dtsch Arztebl Int. 113 (9): 150–7, quiz 158. doi:10.3238/arztebl.2016.0150. PMC 4802357. PMID 26987468.
- ↑ Kaya F, Kocyigit A, Kaya C, Turkcuer I, Serinken M, Karabulut N (March 2015). "Brucellar Testicular Abscess Presenting as a Testicular Mass: Can Color Doppler Sonography be used in Differentiation?". Turk J Emerg Med. 15 (1): 43–6. doi:10.5505/1304.7361.2014.82698. PMC 4909939. PMID 27331193.
- ↑ Navarro-Martínez A, Solera J, Corredoira J, Beato JL, Martínez-Alfaro E, Atiénzar M, Ariza J (December 2001). "Epididymoorchitis due to Brucella mellitensis: a retrospective study of 59 patients". Clin. Infect. Dis. 33 (12): 2017–22. doi:10.1086/324489. PMID 11698991.
- ↑ Colmenero JD, Muñoz-Roca NL, Bermudez P, Plata A, Villalobos A, Reguera JM (April 2007). "Clinical findings, diagnostic approach, and outcome of Brucella melitensis epididymo-orchitis". Diagn. Microbiol. Infect. Dis. 57 (4): 367–72. doi:10.1016/j.diagmicrobio.2006.09.008. PMID 17141451.
- ↑ Reisman EM, Colquitt LA, Childers J, Preminger GM (April 1990). "Brucella orchitis: a rare cause of testicular enlargement". J. Urol. 143 (4): 821–2. PMID 2313817.
- ↑ Rakha E, Puls F, Saidul I, Furness P (August 2006). "Torsion of the testicular appendix: importance of associated acute inflammation". J. Clin. Pathol. 59 (8): 831–4. doi:10.1136/jcp.2005.034603. PMC 1860437. PMID 16569689.
- ↑ Kadish HA, Bolte RG (July 1998). "A retrospective review of pediatric patients with epididymitis, testicular torsion, and torsion of testicular appendages". Pediatrics. 102 (1 Pt 1): 73–6. PMID 9651416.
- ↑ Okui N, Tomita K, Kimura A, Uekane K, Kawamura T, Teshima S (September 1994). "[Heterochronic occurrence of bilateral torsion of appendix testis a case report]". Nippon Hinyokika Gakkai Zasshi (in Japanese). 85 (9): 1395–8. PMID 7967303.
- ↑ Lev M, Ramon J, Mor Y, Jacobson JM, Soudack M (October 2015). "Sonographic appearances of torsion of the appendix testis and appendix epididymis in children". J Clin Ultrasound. 43 (8): 485–9. doi:10.1002/jcu.22265. PMID 25704247.
- ↑ Choong CS, Liew KL, Liu PN, Kuo TU, Su CM (July 2000). "Acute scrotum in Henoch-Schönlein purpura". Zhonghua Yi Xue Za Zhi (Taipei). 63 (7): 577–80. PMID 10934812.
- ↑ Modi S, Mohan M, Jennings A (May 2016). "Acute Scrotal Swelling in Henoch-Schonlein Purpura: Case Report and Review of the Literature". Urol Case Rep. 6: 9–11. doi:10.1016/j.eucr.2016.01.004. PMC 4855902. PMID 27169017.
- ↑ Dayanir YO, Akdilli A, Karaman CZ, Sönmez F, Karaman G (2001). "Epididymoorchitis mimicking testicular torsion in Henoch-Schönlein purpura". Eur Radiol. 11 (11): 2267–9. doi:10.1007/s003300100843. PMID 11702171.
- ↑ Akgun C (2012). "A case of scrotal swelling mimicking testicular torsion preceding Henoch-Schönlein vasculitis". Bratisl Lek Listy. 113 (6): 382–3. PMID 22693978.
- ↑ Voelzke BB, Hagedorn JC (April 2018). "Presentation and Diagnosis of Fournier Gangrene". Urology. 114: 8–13. doi:10.1016/j.urology.2017.10.031. PMID 29146218.
- ↑ Huang CS (March 2017). "Fournier's Gangrene". N. Engl. J. Med. 376 (12): 1158. doi:10.1056/NEJMicm1609306. PMID 28328332.
- ↑ Yücel M, Özpek A, Başak F, Kılıç A, Ünal E, Yüksekdağ S, Acar A, Baş G (September 2017). "Fournier's gangrene: A retrospective analysis of 25 patients". Ulus Travma Acil Cerrahi Derg. 23 (5): 400–404. doi:10.5505/tjtes.2017.01678. PMID 29052826.
- ↑ Namkoong H, Ishii M, Koizumi M, Betsuyaku T (February 2016). "Fournier's gangrene: a surgical emergency". Infection. 44 (1): 143–4. doi:10.1007/s15010-015-0816-4. PMID 26138056.
- ↑ Hagerman RJ, McBogg P, Hagerman PJ (June 1983). "The fragile X syndrome: history, diagnosis, and treatment". J Dev Behav Pediatr. 4 (2): 122–30. PMID 6348096.
- ↑ de Vries BB, Halley DJ, Oostra BA, Niermeijer MF (July 1998). "The fragile X syndrome". J. Med. Genet. 35 (7): 579–89. PMC 1051369. PMID 9678703.
- ↑ Lachiewicz AM, Dawson DV (June 1994). "Do young boys with fragile X syndrome have macroorchidism?". Pediatrics. 93 (6 Pt 1): 992–5. PMID 8190590.
- ↑ Saldarriaga W, Tassone F, González-Teshima LY, Forero-Forero JV, Ayala-Zapata S, Hagerman R (2014). "Fragile X syndrome". Colomb. Med. 45 (4): 190–8. PMC 4350386. PMID 25767309.
- ↑ Shen J, Bi Y, Wang X, Lu L, Tang L, Liu Y, Chen H, Zhang B (December 2017). "Epidemiologic study of 230 cases of testicular/paratesticular tumors or masses: 15-year experience of a single center". J. Pediatr. Surg. 52 (12): 2056–2060. doi:10.1016/j.jpedsurg.2017.08.027. PMID 28967388.
- ↑ Hohšteter M, Artuković B, Severin K, Kurilj AG, Beck A, Šoštarić-Zuckermann IC, Grabarević Ž (August 2014). "Canine testicular tumors: two types of seminomas can be differentiated by immunohistochemistry". BMC Vet. Res. 10: 169. doi:10.1186/s12917-014-0169-8. PMC 4129470. PMID 25096628.
- ↑ McDonald MW, Reed AB, Tran PT, Evans LA (2012). "Testicular tumor ultrasound characteristics and association with histopathology". Urol. Int. 89 (2): 196–202. doi:10.1159/000338771. PMID 22677786.
- ↑ Naouar S, Braiek S, El Kamel R (June 2017). "Testicular tumors of adrenogenital syndrome: From physiopathology to therapy". Presse Med. 46 (6 Pt 1): 572–578. doi:10.1016/j.lpm.2017.05.006. PMID 28549629.
- ↑ Costantino E, Ganesan GS, Plaire JC (May 2017). "Abdominoscrotal hydrocele in an infant boy". BMJ Case Rep. 2017. doi:10.1136/bcr-2017-220370. PMID 28551604.
- ↑ Kaefer M, Agarwal D, Misseri R, Whittam B, Hubert K, Szymanski K, Rink R, Cain MP (October 2016). "Treatment of contralateral hydrocele in neonatal testicular torsion: Is less more?". J Pediatr Urol. 12 (5): 306.e1–306.e4. doi:10.1016/j.jpurol.2015.07.009. PMID 26708803.
- ↑ Yang DM, Kim HC, Lim JW, Jin W, Ryu CW, Kim GY, Cho H (2007). "Sonographic findings of groin masses". J Ultrasound Med. 26 (5): 605–14. PMID 17460003.
- ↑ Chen Y, Wang F, Zhong H, Zhao J, Li Y, Shi Z (December 2017). "A systematic review and meta-analysis concerning single-site laparoscopic percutaneous extraperitoneal closure for pediatric inguinal hernia and hydrocele". Surg Endosc. 31 (12): 4888–4901. doi:10.1007/s00464-017-5491-3. PMID 28389795.
- ↑ 55.0 55.1 Rioja J, Sánchez-Margallo FM, Usón J, Rioja LA (June 2011). "Adult hydrocele and spermatocele". BJU Int. 107 (11): 1852–64. doi:10.1111/j.1464-410X.2011.10353.x. PMID 21592287.
- ↑ Clavijo RI, Carrasquillo R, Ramasamy R (September 2017). "Varicoceles: prevalence and pathogenesis in adult men". Fertil. Steril. 108 (3): 364–369. doi:10.1016/j.fertnstert.2017.06.036. PMID 28865534.
- ↑ Yang DM, Kim HC, Lim JW, Jin W, Ryu CW, Kim GY, Cho H (2007). "Sonographic findings of groin masses". J Ultrasound Med. 26 (5): 605–14. PMID 17460003.
- ↑ Locke JA, Noparast M, Afshar K (October 2017). "Treatment of varicocele in children and adolescents: A systematic review and meta-analysis of randomized controlled trials". J Pediatr Urol. 13 (5): 437–445. doi:10.1016/j.jpurol.2017.07.008. PMID 28851509.
- ↑ Shridharani A, Owen RC, Elkelany OO, Kim ED (2016). "The significance of clinical practice guidelines on adult varicocele detection and management". Asian J. Androl. 18 (2): 269–75. doi:10.4103/1008-682X.172641. PMID 26806081.
- ↑ Yang DM, Kim HC, Lim JW, Jin W, Ryu CW, Kim GY, Cho H (2007). "Sonographic findings of groin masses". J Ultrasound Med. 26 (5): 605–14. PMID 17460003.
- ↑ Yeh HC, Wang CJ, Liu CC, Wu WJ, Chou YH, Huang CH (July 2007). "Giant spermatocele mimicking hydrocele: a case report". Kaohsiung J. Med. Sci. 23 (7): 366–9. doi:10.1016/S1607-551X(09)70423-1. PMID 17606432.
- ↑ Geffre M, Maki C, Maier S (March 2017). "Acute Scrotal Edema in Cirrhotic after Laparoscopic Cholecystectomy". Am Surg. 83 (3): e93–95. PMID 28316300.
- ↑ Esposito F, Sanchez O, Siebert JN, Manzano S (October 2018). "Acute scrotal idiopathic edema: A misleading erythema". CJEM. 20 (S2): S37. doi:10.1017/cem.2017.343. PMID 28625172.
- ↑ Solanki A, Narang S, Kathpalia R, Goel A (September 2015). "Scrotal calcinosis: pathogenetic link with epidermal cyst". BMJ Case Rep. 2015. doi:10.1136/bcr-2015-211163. PMC 4593290. PMID 26400592.
- ↑ Prasad KK, Manjunath RD (August 2014). "Multiple epidermal cysts of scrotum". Indian J. Med. Res. 140 (2): 318. PMC 4216510. PMID 25297369.
- ↑ Ząbkowski T, Wajszczuk M (July 2014). "Epidermoid cyst of the scrotum: a clinical case". Urol J. 11 (3): 1706–9. PMID 25015622.
- ↑ Casasola Chamorro J, Gutiérrez García S, de Blas Gómez V (July 2011). "Scrotal carcinoma". Arch. Esp. Urol. 64 (6): 541–3. PMID 21791720.
- ↑ Halfya A, Elmortaji K, Redouane R, Fethi M, Rafik A, Mohamed E, Abdessamad C (2015). "[Squamous cell carcinomas of the scrotum: about 7 cases with review of the literature]". Pan Afr Med J (in French). 20: 163. doi:10.11604/pamj.2015.20.163.5991. PMC 4469445. PMID 26113906.
- ↑ Armas-Alvarez AL, Salinas-Sánchez AS, Atienzar-Tobarra M, Virseda-Rodríguez JA (March 2016). "Scrotal tumors". Arch. Esp. Urol. 69 (2): 86–9. PMID 26959967.
- ↑ Otabil KB, Tenkorang SB (March 2015). "Filarial hydrocele: a neglected condition of a neglected tropical disease". J Infect Dev Ctries. 9 (5): 456–62. doi:10.3855/jidc.5346. PMID 25989164.
- ↑ Janssen KM, Willis CJ, Anderson M, Gelnett MS, Wickersham EL, Brand TC (July 2017). "Filariasis Orchitis-Differential for Acute Scrotum Pathology". Urol Case Rep. 13: 117–119. doi:10.1016/j.eucr.2017.04.002. PMC 5426035. PMID 28507911.
- ↑ Yagain K, Mathew M (February 2011). "Filariasis presenting as a scrotal nodule in a 2 year old child: a case report". Asian Pac J Trop Med. 4 (2): 167–8. doi:10.1016/S1995-7645(11)60062-X. PMID 21771446.
- ↑ Khallouk A, Yazami OE, Mellas S, Tazi MF, El Fassi J, Farih MH (2011). "Idiopathic scrotal calcinosis: a non-elucidated pathogenesis and its surgical treatment". Rev Urol. 13 (2): 95–7. PMC 3176555. PMID 21935341.
- ↑ Noël B, Bron C, Künzle N, De Heller M, Panizzon RG (July 2006). "Multiple nodules of the scrotum: histopathological findings and surgical procedure. A study of five cases". J Eur Acad Dermatol Venereol. 20 (6): 707–10. doi:10.1111/j.1468-3083.2006.01578.x. PMID 16836500.
- ↑ Polk P, McCutchen WT, Phillips JG, Biggs PJ (September 1996). "Polypoid scrotal calcinosis: an uncommon variant of scrotal calcinosis". South. Med. J. 89 (9): 896–7. PMID 8790314.