Psoriasis is a chronic inflammato-

ry disease that affects primarily the

skin and some of these patients may

develop psoriatic arthritis. 1-3% of

the general population worldwide

were affected by psoriasis, with peak

onset occurs between the ages of 16

to 22 years old and at 57 to 60 years

old. The most common form of psori-

asis is chronic plaque psoriasis, also

known as psoriasis vulgaris. Its clini-

cal features include raised, well-

defined inflamed skin lesions

(plaques) with silvery – white scale.

Due to the increased loss of water

through the affected epidermis, the

lesions tend to be itchy. The lesions

may also turn into painful fissures or

cracks. Apart from physical discom-

fort, patients may suffer from psycho-

social issues because of the highly

visible nature of the disease impact-

ing on their daily activities, social in-

teractions and ability to work.

Pathophysiology of Psoriasis

The exact cause of psoriasis is not fully

understood yet, but current evidence

showed that it involves an autoimmune

process described below:

Trigger factors (see page 3) induce

clonal expansion of T cells in lymph

node.

When T cells being reactivated after

entering dermis and epidermis, they

release cytokines that cause hyper-

propliferation of keratinocytes.

Therefore, new skin cells differenti-

ate and mature over 7 days in psoria-

sis patients compared to 28 days for

normal people. The abnormal turno-

ver and buildup of skin cells cause

the formation of psoriatic plaques.

Decreased release of lipids at the

skin surface lead to flaking, scaly

presentation.

Increased number and size of dermal

blood vessels cause the redness be-

neath psoriatic plaques.

Figure 1 Pathophysiology of Psoria-

sis

PSORIASIS

I N S I D E T H I S

I S S U E :

PSORIASIS 1-7

ADR Sept–

Dis 2013

8

MADRAC

UPDATE

9-11

FDA SAFETY

UPDATE

12

ANNOUNCE-

MENT

13

ACTIVITY OF

PHARMACY

DEPARTMENT

14

BULLETIN PHARMACY V O L U M E 4 / 2 0 1 3

EDITORIAL

BOARD

Advisor : Pn Siti Asmah Basi-

min

Editor : Tan Lay Chai

Co-editor 1.Khoo Chee Shin

2.Tai Ann Nny

3.Nur Syahirah Bt

Abd Raof

HS

FARMASI

PHARMACY

DEPARTMENT

HOSPITAL

SEGAMAT

P A G E 2

Table 1: Classification of Psoriasis Type of

Psoriasis

Description

Psoriasis

vulgaris

Most common form (80-90% of patients)

Well-defined, inflamed plaques with silvery scale typically on

the lower back, knees and elbows

Flexural

psoriasis

Distinct reddened patches in body folds and flexures with min-

imal scaling because these areas tend to be moist

May occur alone or can be accompanied by plaques in other

body parts

Scalp psoriasis Present in about 50% of people with psoriasis

May present as discrete plaques or more profuse scale

extending beyond the hairline

Guttate

psoriasis

Acute form of psoriasis often triggered by upper respiratory

tract streptococcal infections

A sudden eruption of small inflamed lesions with a fine scale

usually develop over the trunk and limbs, and sometimes on

the face and scalp

May resolve spontaneously or require treatment

Nail psoriasis Can be associated with all types of psoriasis

Include yellow-brown discoloration, pitting, nail crumbling,

thickened nails

Fingernails are more commonly affected than toenails

Pustular

psoriasis

Localised: small, fluid-filled blisters (pustules) form on the

palms of the hands and soles of the feet, they do not rupture but

become a dark brown colour with scale as they reach the

surface and may be painful

Generalised: uncommon, but may be accompanied by fever and

tenderness, and requires immediate medical attention

Erythrodermic

psoriasis

Painful, generalised red rash develop over a large area of the

body and may be accompanied by a fever

Peeling and blistering of the skin can also occur

Rare but serious and needs urgent medical attention

May develop gradually from psoriasis vulgaris or acutely with

no previous skin lesions

Psoriatic arthritis Up to 50% of psoriasis patients may develop inflammatory

arthritis

Commonly affects joints in hands and lower spine

Symptoms include pain, swelling and stiffness

Similar to rheumatoid arthritis but rheumatoid factor antibody

is absent

Figure 2

Psoriasis vulgaris on

both knees

Figure 3

Flexural psoriasis at

armpit

Figure 4

Scalp psoriasis

Figure 5

Guttate psoriasis

P A G E 3

Risk and Trigger Factors

B U L L E T I N P H A R M A C Y

Figure 6

Nail changes in

psoriasis

Figure 7

Pustular psoriasis

on the palm of left

hand

Figure 8

Life-threatening

erythrodermic

psoriasis

Factors that may contribute to the

onset of psoriasis and trigger future

exacerbations:

Family history of psoriasis

Recent infection eg.

streptococcal infection

Trauma/injury to the skin

Personal history of skin

disorder

Sunburn

Seasonal changes in weather

Obesity

Smoking

Emotional stress

Excessive alcohol intake

Medicines

Medicines that have been reported

to trigger or exacerbate psoriasis:

Beta blockers

Lithium

Hydroxychloroquine

ACE inhibitors

Indomethacin

Terbinafine

Interferon alfa-2b

Amiodarone

Oral corticosteroids (on

cessation)

Citalopram, escitalopram

Psoriasis is associated with an increased risk of numerous co-morbidities particularly

metabolic syndrome and atherosclerosis-related diseases. Psoriasis patients have

significant risk of developing metabolic abnormalities such as abdominal obesity,

dyslipidaemia and diabetes mellitus. Atherosclerosis-related diseases that are associ-

ated with psoriasis includes ischemic heart disease and stroke. It is postulated that the

increased risk of cardiovascular disease is due to coronary artery calcification caused

by the chronic inflammatory process involved in psoriasis.

Psoriasis is also linked with elevated risk of developing autoimmune diseases such as

inflammatory bowel disease. Besides that, patients with severe psoriasis have higher

risk of depression and anxiety which could lead to suicide. Although psoriasis has

been associated with greater chance of skin cancer, it is uncertain that this is caused

by the disease itself or the phototherapy treatment.

Medical Co-morbidities

Figure 9 Koebner phenomenon

Psoriatic lesion appear at a site

of injury after localised trauma

V O L U M E 4 / 2 0 1 3 P A G E 4

Management of Psoriasis Psoriasis can be managed by lifestyle modifications

such as stress management, and pharmacological

treatments which include topical treatments,

phototherapy and systemic therapies. Although

psoriasis is not curable, available treatments help to

control symptoms and induce remission.

The choice of treatment depends on the severity of the

disease, the sites affected and the impact of the disease

on the quality of life. Table 2 shows the assessment of

severity of psoriasis based on the body surface area

(BSA), Psoriasis Area & Severity Index (PASI), and

Dermatology Life Quality Index (DLQI). Mild to

moderate with minimal impact on the quality of life

can be managed with topical treatments either

monotherapy or a combination of therapies which have

different mechanisms of action. As for psoriasis which

is severe, involves extensive areas or greatly reduces

patients’ quality of life, dermatologists may

recommend phototherapy or systemic agents.

Table 2 Severity of Psoriasis

Severity BSA PASI DLQI

Mild < 10% < 10 < 6

Moderate 10-29% 10-19 6-17

Severe ≥ 30% ≥ 20 ≥ 18

Coal tar is used to treat limited or scalp psoriasis due

to its anti-inflammatory and anti-pruritic properties.

Coal tar formulated in shampoo may be used twice

weekly up to once daily for scalp psoriasis. Coal tar

cream, lotion or gel can be applied once to three times

daily but it should be avoided on face, skin flexures

and genitals due to possible irritation. It is important to

prevent sunlight exposure for 24 hours after

application of coal tar because it causes

photosensitivity. Patients may less likely to adhere to

coal tar therapy due to its unpleasant smell. It also

stains the skin, hair or clothing.

Dithranol is useful, for treating thick plaque psoriasis

as it helps to reduce the rate of epidermal cell

proliferation. Dithranol 0.1-0.5% in ointment or paste

is suitable for overnight treatment, while 1-2% is used

for short contact treatment up to 1 hour. It should be

avoided on face, skin flexures and genitals because it

may cause local burning sensation and irritation. Like

coal tar, it also stains the skin, hair and clothing.

Topical Therapies

Topical treatments have minimal side effects

compared to systemic therapies but their efficacy

highly depends on the adherence to the treatments.

They are formulated as creams, ointments, lotions, gels

and shampoos. The choice of formulation depends on

the site of application. For an instance, gels or lotions

may be preferred for hairy areas. Topical treatments

available for psoriasis include emollients, keratolytics,

coal tar, dithranol, corticosteroids and calcipotriol.

Emollients such as aqueous cream and white soft

paraffin should be used regularly as a soap or applied

to the skin twice daily. Emollients hydrate and soften

the plaques to reduce itchiness, scaling and cracking of

the skin.

Salicylic acid, a keratolytic, helps to remove scale on

the skin or scalp. Therefore, it increases penetration of

other topical agents such as coal tar, dithranol and

corticosteroids when used in combination with these

agents. However, it can cause skin irritation and

redness.

Topical corticosteroids are used in the treatment of

psoriasis because they inhibit cytokine production,

thus reducing inflammation and the rate of epidermal

cell proliferation. They act quicker to clear the plaques

than coal tar and dithranol but remission period may be

shorter. Less potent agent such as hydrocortisone 0.5-

1% may be applied to face and flexures once to twice

daily up to 1 week. More potent agents such as

betamethasone valerate 0.01-0.1% and clobetasol

propionate 0.05% may be applied to other areas once

to twice daily for no more than 4 weeks. Occasionally,

topical corticosteroids may be used with occlusive

dressing under supervision of dermatologist to help

increase penetration into thick plaque. The risk of local

side effects such as skin thinning and allergic contact

dermatitis increases with prolonged use of topical

corticosteroids. Although systemic side effects are rare

with topical corticosteroids, it is recommended to

reduce the frequency of application or change to less

potent agent once the condition is controlled. Topical

corticosteroids are contraindicated for patients who

have untreated bacterial, fungal or viral skin lesions.

Figure 10 Fingertip unit (FTU)

rule for topical corticosteroids

and calcipotriol

1 FTU = 0.5g and should cover

an area equivalent to the size of

two hand palms of the patient

V O L U M E 4 / 2 0 1 3 P A G E 5

Management of Psoriasis Calcipotriol is a synthetic analogue of vitamin D used

to treat chronic stable plaque psoriasis and scalp

psoriasis. It reduces the rate of epidermal cell division

by binding to vitamin D receptors. It is available as

50mcg/g cream or ointment to be applied once daily up

to 100g weekly. It is also available as 50mcg/ml scalp

solution to be used twice daily up to 60ml weekly. It

may take up to 6 weeks of continuous use to get

desired improvement in symptoms. Avoid use on face

because local adverse effects of calcipotriol include

itching, burning, dryness and erythema. However, they

usually subside with continued use. Systemic adverse

effects such as hypercalcaemia may occur due to

application more than recommended dosage or

existing renal impairment. Patients should be advised

to avoid exposure to sunlight and sunlamps because

ultraviolet A (UVA) radiation can inactivate

calcipotriol. There is also a combination product

containing calcipotriol 50mcg/g and betamethasone

dipropionate 0.5mg/g ointment which is indicated for

resistant plaque psoriasis. It can be applied once daily

to maximum 30% of body surface up to 4 weeks with

maximum 100g per week. This combination has been

shown to be more effective than calcipotriol or

betamethasone alone.

Phototherapy

Phototherapy is indicated for moderate to severe

psoriasis which is not adequately controlled by topical

therapies. During treatment, patients are exposed to

controlled doses of artificial UV radiation which have

local immunosuppressive and anti-inflammatory

actions. Phototherapy is usually administered 2 to 3

times per week for a total of 20 to 25 sessions. About 6

weeks of phototherapy can induce remission that lasts

for 3 to 6 months. Local side effects include itching,

burning, erythema and hyperpigmentation. Long term

cumulative doses may increase the risk of skin cancer.

Systemic Agents

If phototherapy fails, or is contraindicated/unavailable,

a systemic agent is an alternative option for moderate

to severe psoriasis. All systemic agents have serious

side effects, therefore patients should be assessed for

their risk of side effects by baseline laboratory tests

before starting the treatment and are monitored

regularly during treatment. Besides conventional

systemic agents such as methotrexate, acitretin and

cyclosporine, newer biological agents are also

available. Dosage and monitoring of these systemic

agents are listed in Table 3.

Methotrexate is the most commonly prescribed

systemic agent for plaque psoriasis. It is a folate

antagonist that has antiproliferative and

immunosuppressive actions. It is administered either

orally or intramuscularly/subcutaneously once weekly. It

has slow onset of action, taking at least 3 months to

induce remission. Folate supplementation (5mg daily

except on the day of methotrexate dosing) is required to

reduce bone marrow suppression and gastrointestinal

side effects such as nausea and stomatitis. Slow dose

titration and regular blood tests are essential to prevent

hematological and liver toxicity. Methotrexate is

contraindicated in pre-existing blood dyscrasias, liver

disease, severe renal impairment and pregnancy.

Acitretin is an oral vitamin A analogue which has anti-

inflammatory effect and reduces the rate of epidermal

cell turnover. As it is not immunosuppressive, it may be

an alternative treatment for HIV patients with psoriasis

where phototherapy is not feasible. Acitretin is used as

single agent or in combination with topical therapies.

Side effects include hair loss, skin peeling, elevated

fasting blood glucose, hypercholesterolemia and elevated

liver function tests. Women of childbearing age should

avoid pregnancy for at least 1 month before, during and

for at least 3 years after treatment due to teratogenic

effect. Other contraindications include concurrent use

with methotrexate or tetracycline, breastfeeding and

severe liver or renal impairment.

Cyclosporine is an oral calcineurin inhibitor which has

immunosuppressive action. It can rapidly induce

remission in 6 to 12 weeks of treatment and is useful for

resistant plaque psoriasis which is not responding to

methotrexate. Side effects including hypertension, renal

toxicity, hypercholesterolemia, hyperuricemia,

periodontal diseases and malignancy concern usually

limit the duration of cyclosporine therapy to maximum

of 2 years. Cyclosporine is contraindicated in abnormal

renal function, uncontrolled hypertension, malignancies,

and concurrent use with other immunosuppressive

agents, phototherapy or coal tar therapy.

Figure 11

Cabinet for phototherapy

to treat psoriasis that

affects extensive areas

Drug Initial Dose Maintenance dose Monitoring

Methotrexate 2.5-5mg once

weekly

Increased by 2.5 to 5mg

every 2-4 weeks based

on clinical response or

toxicity

Maximum 25mg once

weekly

FBC, LFT, RP

2 weeks after starting

Monthly for the first 3

months, then every 2-3

months

Acitretin 25-30mg once daily

for 2-4 weeks

Adjust based on

response

Usually within 25-50mg

daily

Maximum 75mg daily

LFT, lipid profile

Every 4 weeks until

stable, then every 6-12

weeks

Cyclosporine 2.5mg/kg/day

divided into two

doses

Increased by 0.5mg/kg/

day if insufficient

response after 4 weeks

Additional dose

increases may be made

every 2 weeks if

necessary

Maximum 4mg/kg/day

BP, LFT, RP, lipid

profile

Monthly for the first 3

months, then every 2-3

months

Adalimumab 80mg followed by

40mg 1 week later

40mg every other week Baseline FBC, LFT,

RP, hepatitis test, TB

test

Etanercept 50mg twice weekly

(72-96 hours apart)

for first 3 months

50mg weekly

Infliximab 5mg/kg at 0, 2 and 6

weeks

5mg/kg every 8 weeks

Ustekinumab Patients weighing

≤100kg: 45mg

>100kg: 90mg

Given at week 0 and

4

Same dose given every 12

weeks

Table 3 Dosage and Monitoring of Systemic Agents P A G E 6

Biological agents are monoclonal antibodies that

block specific molecules involved in the

immunologic process of psoriasis such as tumor

necrosis factor alpha (TNF-α) and interleukins.

There are 4 biological agents available in

Malaysia for psoriasis: adalimumab, etanercept

and infliximab which are TNF-α inhibitors, and

ustekinumab which is an interleukin-12 and

interleukin-23 inhibitor. Adalimumab, etanercept

and ustekinumab are administered

subcutaneously while infliximab is administered

as intravenous infusion. Theoretically, they may

be less toxic to the liver, kidney and bone marrow

compared to conventional systemic agents and

need less monitoring. However, they are

expensive and their long term safety profile is not

well-established yet. Therefore, biologic therapy

is only indicated for patients with severe psoriasis

defined by BSA ≥30 or PASI ≥20 or DLQI ≥18

and have failed, intolerance or contraindication to

conventional systemic treatment and

phototherapy. Most patients respond within 4

weeks and show a significant improvement in

symptoms by 12 weeks.

These agents are contraindicated in the

following:

Active infection

Current and/or previous history of

tuberculosis

HIV infection

Hepatitis B/C

Current and/or previous history of

malignancy

Congestive cardiac failure

Demyelinating diseases

Intention to get pregnant

Pregnancy or breast-feeding

Patient who have had prior PUVA (>200

sessions) and UVB (>350 sessions)

1. Ministry of Health Malaysia. Clinical Practice Guideline: Management of psoriasis

vulgaris 2013.

2. Thompson M. Psoriasis. InPHARMation 2012; 13(1): 6-11. Pharmaceutical Society of

Australia.

3. Berth-Jones J. Psoriasis. In: Medical Progress. 2011. Available from: http://

www.mims.com/Malaysia/pub/topic/Medical%20Progress/2011-04/Psoriasis%20 4. Drugs for psoriasis. Australian Medicine Handbook. 2010.

5. Sullivan JR, Preda VA. Treatment for severe psoriasis. Aust Prescr. 2009; 32(1): 14-18.

References

P A G E 7

ADVERSE DRUG REACTION HOSPITAL SEGAMAT SEPTEMBER– DISEMBER 2013

DATE MEDICATIONS ADR TREATMENT REPORTER

2.9.13 calcium carbonate 500mg patient complained of dizziness and body weakness after taking Calcarb 1g bd, patient never had these problem while on calcium carbonate MPI 1g bd previously.

stop the drug Khoo Chee Shin

11.9.13 hepatitis B vaccine (2nd dose) patient developed urticaria rash starting from face, then spread to trunk and both lower limb also a/w bilateral foot swelling, but no rapid breathing/cyanosis dan tolerate orally

syrup prednisolone Dr Nor Hamraa binti Saruan

26.9.13 glucovance 1 tab 500mg bd (suspect glibenclamide cause increasing ALT & AST level as metformin given in the ward and both level showing decreasing trend)

patient's ALT 974.80-->636.9 --> 443.3 AST 520.90--> 88.7 --> 35.6 patient has acute hepatitis

discontinue gluco-vance, only start metformin without glibenclamide

Lee Ley Chen

27.9.13 T. Chlopromazine 100mg Atlantic laboratories corporation Ltd.

patient claimed insomnia since switching from T. Chlopromazine 100mg (Idaman pharma manufac-turing) to (atlantic laboratories cor-poration Ltd.) Patient never had this problem while on T. Chlopromazine idaman pharma manuf.

exchange to T. chlo-promazine 100mg (idaman pharma manuf)

Noziyani Abu Hassan

8.10.13 T. Eperisone 50mg patient complained of difficulty in breathing, tired, insomnia, depres-sion, suicidal thoughts and panic attack

stop medication Soh Wei San

8.10.13 S/C Mixtard patient developed urticaria rash all over the back of body since switch-ing from S/C humulin 30/70 to S/C Mixtard 30 (Novonordisk)

change to Novomix Tan Lay Chai

14.11.13 I.v metoclopramide Oculogyric crisis Procyclidine 10mg stat

Lee Ley Chen

15.11.13 Sy. Erythromycin urticaria,itchiness, redness and eye swelling

Change to Sy. Chlor-pheniramine

Dr. Nur Liyana Omar

19.11.13 Dapsone Following lab and ultrasound inves-tigation: it was diagnosed as gall-stone pancreatitis with paralytic ile-us

. Khoo Chee Shin

26.12.13 T.Cloxacillin 250 mg tds and Di-clofenac sodium SR I/I OD

generalized itchiness and rash and shortness of breath for 1 hour

iv Hyrocortisone 200 mg stat, IV piriton 10 mg stat and T. piriton 4 mg tds for 3 days

Dr. Raja Nur Atikah bt Raja Azman

P A G E 8

P A G E 9

V O L U M E 4 / 2 0 1 3

P A G E 1 0

V O L U M E 4 / 2 0 1 3

P A G E 1 1

V O L U M E 4 / 2 0 1 3

FDA Drug Safety Communication: FDA limits usage of

Nizoral (ketoconazole) oral tablets due to potentially fatal

liver injury and risk of drug interactions and adrenal

The U.S. Food and Drug Administration (FDA) is taking several actions related to Nizoral (ketoconazole) oral tablets, including limiting the drug’s use, warning that it can cause severe liver injuries and adrenal gland problems and advising that it can lead to harmful drug interac-tions with other medications. FDA has approved label changes and added a new Medication Guide to address these safety issues. As a result, Nizoral oral tablets should not be a first-line treatment for any fungal infection. Nizoral should be used for the treatment of certain fungal infections, known as endemic mycoses, only when alternative antifungal therapies are not available or tolerated.

The topical formulations of Nizoral have not been associated with liver damage, adrenal prob-

lems, or drug interactions. These formulations include creams, shampoos, foams, and gels ap-

plied to the skin, unlike the Nizoral tablets, which are taken by mouth.

Liver Injury (Hepatotoxicity)

Nizoral tablets can cause liver injury, which may potentially result in liver transplantation or death. FDA has revised the Boxed Warning, added a strong recommendation against its use (contraindication) in patients with liver disease, and included new recommendations for as-sessing and monitoring patients for liver toxicity.

Serious liver damage has occurred in patients receiving high doses of Nizoral for short periods of time as well as those receiving low doses for long periods. Some of these patients had no obvious risk factors for liver disease. The liver injury is sometimes reversible upon stopping the drug, but that is not always possible.

Adrenal Gland Problems (Adrenal Insufficiency)

Nizoral tablets may cause adrenal insufficiency by decreasing the body’s production of hor-mones called corticosteroids. Corticosteroids are produced by the adrenal glands, which are small glands located on top of each kidney. Corticosteroids affect the body’s balance of water and salts and minerals (electrolytes). Health care professionals should monitor adrenal func-tion in patients taking Nizoral tablets who have existing adrenal problems or in patients who are under prolonged periods of stress such as those who have had a recent major surgery or who are under intensive care in the hospital.

V O L U M E 4 / 2 0 1 3 P A G E 1 2

Drug Interactions Nizoral tablets may interact with other drugs a patient is taking and can result in serious and potentially life-threatening outcomes, such as heart rhythm problems. All medications that a patient is currently tak-

ing should be assessed for possible interactions with Nizoral tablets.

In summary, the drug label for Nizoral tablets has been updated to include the following information:

Limitation of the usage of Nizoral tablets by removing indications in which the risk outweighs the ben-efits. The use of ketoconazole tablets in Candida and dermatophyte infections is no longer indicated. Nizoral tablets should be used only when other antifungal drugs are not available or tolerated by the pa-tient.

Nizoral tablets are indicated only for the treatment of the following fungal infections: blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis in patients in whom other treatments have failed or who are intolerant to other therapies.

Nizoral tablets are not indicated for the treatment of fungal infections of the skin or nails.

A new contraindication that Nizoral tablets should not be used in patients with acute or chronic liver disease.

For more information, please review: http://www.fda.gov/Drugs/DrugSafety/ucm362415.htm

Pegawai Farmasi U41 (FRP)

1) Mira Marina Binti Mahfodz

2) Wan Farhah Adiba Binti Wan Abd Ghafar

3) Tan Yew Jin

Pegawai Farmasi U41 (PRP)

1) Noorul Atiqah bt. Ibrahim

2) Chin Mei Ping

3) Norliana Bt Rosli 4) Ummu Zahidah Bt Abu Bakar

5) Syahrina Bt Syahlan

6) Noor Syafika Bt Mohd Ibrahim

7) Zulaikha Bt Ramlee

8) Mohd Azmer B Lias

9) Ahmad Fawwazuddin B. Rozaki 10) Nur Izzati Dhamirah Bt Mohd Yusof

11) Nur Syahirah Bt Abd Raof

Noorulhida Bt. Ishak

for her newnborn baby

P A G E 1 3 V O L U M E 4 / 2 0 1 3

.

ACTIVITIES OF PHARMACY

DEPARTMENT

One booth was opened on Diabetes day

( 18.2.2013)

by pharmacy department to educate patients

about diabetes and its management.

Pharmacists explain to the

participant about diabetes dis-

ease and its management.

Some quiz and gifts also

provided for

participant who can answer

questions correctly.

V O L U M E 4 / 2 0 1 3 P A G E 1 4

P A G E 1 5

V O L U M E 4 / 2 0 1 3