Ivandy Fam 22010112130089 Lap KTI BAB VII

DAFTAR PUSTAKA

1.

Prof. Chairuddin Rasjad, MD. P. Pengantar Ilmu Bedah Ortopedi. 2012.

2.

Pountos I, Georgouli T, Calori GM, Giannoudis P V. Do nonsteroidal antiinflammatory drugs affect bone healing? A critical analysis. Sci World J.
2012;2012:606404.

3.

Kalfas IH. Principles of bone healing. Neurosurg Focus. 2001;10(4):E1.

4.

Yamaji T, Ando K, Wolf S, Augat P, Claes L. The effect of micromovement
on callus formation. J Orthop Sci. 2001;6(6):571–5.

5.


Sathyendra V, Darowish M. Basic science of bone healing. Hand Clin.
2013;29(4):473–81.

6.

Pountos I, Georgouli T, Blokhuis TJ, Pape HC, Giannoudis P V.
Pharmacological agents and impairment of fracture healing: What is the
evidence? Int J Care Inj. 2008;39(4):384–94.

7.

Pountos I, Georgouli T, Bird H, Kontakis G, Giannoudis P V. The effect of
antibiotics on bone healing: current evidence. Expert Opin Drug Saf.
2011;10(6):935–45.

8.

Beck A, Krischak G, Sorg T, Augat P, Farker K, Merkel U, et al. Influence
of diclofenac (group of nonsteroidal anti-inflammatory drugs) on fracture

healing. Arch Orthop Trauma Surg. 2003;123(7):327–32.

9.

Cottrell J, O’Connor JP. Effect of non-steroidal anti-inflammatory drugs on
bone healing. Pharmaceuticals. 2010;3(5):1668–93.

10.

Krischak GD, Augat P, Sorg T, Blakytny R Kinzl L, Claes L, et al. Effects

37

of diclofenac on periosteal callus maturation in osteotomy healing in an
animal model. Arch Orthop Trauma Surg. 2007;127(1):3–9.
11.

Katzung BG. Katzung - Basic and Clinical Pharmacology 12th edition.
2012. 635-658 p.


12.

Zarghi A, Arfaei S. Selective COX-2 Inhibitors: A Review of Their
Structure-Activity Relationships. Iran J Pharm Res IJPR . 2011;10(4):655–
83.

13.

Permata VA. Penggunaan analgesik pasca operasi orthopedi di RSUP dr.
Kariadi semarang. 2014

14.

Tooley A, Vickers H. The adverse effects of intravenous ketorolac related to
postoperative hemorrhage and hematoma in adults aged 18 years and older:
a systematic review protocol. JBI Database Syst Rev Implement Reports .
2014;12(6):3.

15.


Reinhart DJ. Minimising the adverse effects of ketorolac. Drug Saf .
2000;22(6):487–97.

16.

Feldman HI, Kinman JL, Berlin JA, Hennessy S, Kimmel SE, Farrar J, et
al. Parenteral ketorolac: the risk for acute renal failure. Ann Intern Med .
1997;126(3):193–9.

17.

Fracon RN, Teófilo JM, Satin RB, Lamano T. Prostaglandins and bone:
potential risks and benefits related to the use of nonsteroidal antiinflammatory drugs in clinical dentistry. J Oral Sci. 2008;50(3):247–52.

18.

Barry S. Non-steroidal anti-inflammatory drugs inhibit bone healing: A
review. Vet Comp Orthop Traumatol . 2010;23(6):385–92. 19.

Estai


MA, Soelaiman NI, Shuid AN, Das S, Ali AM, Suhaimi FH. Histological
changes in the fracture callus following the administration of water extract
of Piper sarmentosum (Daun Kadok) in estrogen-deficient rats. Iran J Med
Sci. 2011;36(4):281–8.
20.

Zhang X, Schwarz EM, Young DA, Puzas JE, Rosier RN, O'Keefe
RJ. Cyclooxygenase-2 regulates mesenchymal cell differentiation into the
osteoblast lineage and is critically involved in bone repair. J Clin Invest .
2002;109(11):1405–15.

21.

Gerstenfeld LC, Einhorn T a. COX inhibitors and their effects on bone
healing. Expert Opin Drug Saf . 2004;3(2):131–6.

22.

Jurado S, Garcia-Giralt N, Díez-Pérez A, Esbrit P, Yoskovitz G, Agueda L,

et al. Effect of IL-1beta, PGE(2), and TGF-beta1 on the expression of OPG
and RANKL in normal and osteoporotic primary human osteoblasts. J Cell
Biochem. 2010;110(2):304–10.

23.

J.E. Puzas, R.J. O’Keefe, E.M. Schwarz XZ. Pharmacologic modulators of
fracture healing: The role of cyclooxygenase inhibition. J Musculoskel
Neuron Interact. 2003;3(4):308–12.

24.

McAdam BF, Catella-Lawson F, Mardini IA, Kapoor S, Lawson JA,
FitzGerald GA. Systemic biosynthesis of prostacyclin by cyclooxygenase
(COX)-2: the human pharmacology of a selective inhibitor of COX-2. Proc
Natl Acad Sci U S A . 1999;96(1):272–7.

25.

Warner TD, Mitchell J a. Cyclooxygenases: new forms, new inhibitors, and

lessons from the clinic. FASEB J. 2004;18(7):790–804.

26.

FitzGerald G a. COX-2 and beyond: Approaches to prostaglandin inhibition
in human disease. Nat Rev Drug Discov. 2003;2(11):879–90.

27.

Beck A, Salem K, Krischak G, Kinzl L, Bischoff M, Schmelz A.
Nonsteroidal anti-inflammatory drugs (NSAIDs) in the perioperative phase
in traumatology and orthopedics Effects on bone healing. Oper Orthop
Traumatol . 2005;17(6):569–78.

28.

Holdgate A, Pollock T. Systematic review of the relative efficacy of nonsteroidal anti-inflammatory drugs and opioids in the treatment of acute
renal colic. BMJ Br Med J . 2004;328(7453):1401.

29.


Monzón DG, Vazquez J, Jauregui JR, Iserson K V. Pain treatment in posttraumatic hip fracture in the elderly: Regional block vs. systemic nonsteroidal analgesics. Int J Emerg Med. 2010;3(4):321–5.

30.

Holdgate A, Pollock T. Nonsteroidal anti-inflammatory drugs (NSAIDs)
versus opioids for acute renal colic. Cochrane Database Syst Rev.
2005;(2):CD004137.

31.

Ketorolac

Dosage.

[cited

2016

Jan


24].

Available

from:

http://www.drugs.com/dosage/ketorolac.html
32.

Gerstenfeld LC, Thiede M, Siebert K, Mielke C, Phippard D, Svagr B, et
al. Differential inhibition of fracture healing by non-selective and
cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs. J
Orthop Res. 2003;21(4):670–5.

33.

Gerstenfeld LC, Al Ghawas M, Alkhiary YM, Cullinane DM, Krall E a,
Fitch JL, et al. Selective and Nonselective Cyclooxygenase-2 Inhibitors and


Experimental Fracture-Healing. J Bone Jt Surgery, Am Vol

.

2007;89(1):114–25.
34.

Huntjens DRH, Danhof M, Della Pasqua OE. Pharmacokineticpharmacodynamic correlations and biomarkers in the development of
COX-2 inhibitors. Rheumatology. 2005. p. 846–59.

35.

Langford RM, Mehta V. Selective cyclooxygenase inhibition: its role in
pain and anaesthesia. Biomed Pharmacother. 2006;60(7):323–8.

36.

Capello T, Lauing KL, Jagodzinski JE, Callaci JJ. Ketorolac Administration
Does Not Delay Early Fracture Healing in a Juvenile Rat Model: J Pediatr
Orthop. 2014;33(4):415–21.


37.

Woolf CJ: Evidence for a central component of postinjury pain
hypersensitivity. Nature 1983; 308: 686–8

38.

Vadivelu N, Mitra S, Schermer E, Kodumudi V, Kaye AD, Urman RD.
Preventive analgesia for postoperative pain control: a broader concept.
Local and Regional Anesthesia . 2014;7:17-22.

Lampiran 1

METODE BAKU HISTOLOGIS PEMERIKSAAN JARINGAN
(TjartaAchmad, 1992)
A. Cara pengambilan jaringan dan fiksasi
1) Mengambil jaringan sesegera mungkin setelah tikus Wistar dewasa
diterminasi dengan cara pemberian Choloroform dosis sangat
tinggi.
2) Kemudian memasukkan ke dalam larutan fiksasi dan dekalsifier
dengan urutan sebagai berikut :
a) Fiksasi dalam larutan formalin 10%
b) Dekalsifikasi menggunakan TBD-1 rapid declacifier selama 24
jam untuk melunakkan tulang sebelum di masukkan dalam blok
parafin.
c) Xylol paraffin 1:1 selama 20 menit/24 jam dengan dipanaskan
dalam oven 600C.
d) Embedding dan blocking : paraffin 1, 2, 3 selama 20 menit, lalu
jaringan dicetak blok paraffin kemudian didinginkan, sehingga
cetakan dapat dibuka.
e) Trimming : memotong balok-balok paraffin sehingga jaringan
mudah dipotong dengan mikrotom.
B. Cara pemotongan blok (sectioning)
1) Menyiapkan kaca objek bersih.
2) Kaca objek diberi albumin ditengahnya dan direkatkan.
3) Blok yang sudah disiapkan dipotong dengan ketebalan 5

mikron, lalu dimasukkan dalam air panas kurang lebih 600C.
Setelah jaringan mengembang jaringan diambil dengan kaca
objek yang sudah diberi albumin.
4) Kemudian dikeringkan.
5) Paraffin yang ada pada kaca objek atau jaringan dihilangkan
dengan dipanaskan dalam oven 600C atau dengan tungku.
B. Pewarnaan HE
Slide jaringan dimasukkan dalam :
1) Xylol 1, 2, 3 masing-masing 10 menit.
2) Rehidrasi dengan alkohol xylol selama 5 menit.
3) Bilas alkohol 30-96% masing-masing kurang lebih 30 menit.
4) Bilas aquades 1 kali kurang lebih 10 menit.
5) Rendam dalam hematoksilin kurang lebih 10 menit.
6) Bilas dengan air mengalir sampai bersih.
7) Bilas aquades, lalu acid alcohol (alkohol+NaCl 0,9%).
8) Bilas alkohol 50-96%.
9) Eosin kurang lebih 2-5%.
10) Bilas alkohol 96% sebanyak 2 kali.
11) Bilas alkohol xylol.
12) Keringkan dengan kertas saring langsung dibersihkan kotorankotoran yang ada di sekitar jaringan.
13) Xylol 1 (5 menit), xylol 2 (5 menit) tetesi asam canada,
langsung ditutup kaca penutup.
14) Preparat sudah siap untuk diamati di atas mikroskop.

Lampiran 2

Lampiran 3

Lampiran 4. Hasil Pembacaan Slide Penelitian

Lapangan Pandang
Tikus
I

II

III

Kontrol 1

5

5

4

Kontrol 2

5

4

5

Kontrol 3

5

3

4

Kontrol 4

4

4

5

Kontrol 5

5

5

4

Kontrol 6

5

4

4

Kontrol 7

5

3

4

Perlakuan 1

3

3

4

Perlakuan 2

3

4

4

Perlakuan 3

4

4

3

Perlakuan 4

4

4

3

Perlakuan 5

4

3

5

Perlakuan 6

3

3

4

Perlakuan 7

4

4

4

Lampiran 5. Analisis data menggunakan program SPSS

Descriptives
Statistic
Kontrol

Mean

4.3814

95% Confidence Interval for Mean

Lower Bound

4.1024

Upper Bound

4.6604

5% Trimmed Mean

4.3866

Median

4.3300

Variance

.11403

.091

Std. Deviation

.30169

Minimum

4.00

Maximum

4.67

Range

.67

Interquartile Range

.67

Skewness

Perlakuan

Std. Error

-.333

.794

Kurtosis

-1.842

1.587

Mean

3.6671

.10339

95% Confidence Interval for Mean

Lower Bound

3.4142

Upper Bound

3.9201

5% Trimmed Mean

3.6674

Median

3.6700

Variance

.075

Std. Deviation

.27354

Minimum

3.33

Maximum

4.00

Range

.67

Interquartile Range

.67

Skewness
Kurtosis

-.033

.794

-1.200

1.587

Tests of Normality
Kolmogorov-Smirnov
Statistic
Kontrol
Perlakuan

df
.259
.218

a

Shapiro-Wilk
Sig.

Statistic

df

Sig.

7

.170

.818

7

.062

7

*

.858

7

.144

.200

*. This is a lower bound of the true significance.
a. Lilliefors Significance Correction

Group Statistics
Kelompok
Derajat Penyembuhan Fraktur

N

Mean

Std. Deviation

Std. Error Mean

1.00

7

3.6671

.27354

.10339

2.00

7

4.3814

.30169

.11403

Lampiran 6. Dokumentasi Penelitian dan Gambaran Mikroskopis Kalus

Pemberian label pada tikus

Anestesi dengan ketamine IM

Frakturisasi tertutup

Injeksi ketorolac intraperitoneal hari pertama

Blok Paraffin

Pengecatan HE

Skor Allen 3

Skor Allen 4

Skor Allen 5

Skor Allen 5