derm Flashcards
1
Q
Ehlers danos syndrome
A
group of genetically heterogenous connective tissue disorders linked with genetic defects affecting collagen or other extracellular matrix proteins
2
Q
Hereditary equine regional dermal asthenia (HERDA) is seen in what breed
A
American quarter horses
3
Q
Hereditary equine regional dermal asthenia (HERDA) gene mutation
A
PPIB: peptidyl prolyl isomerase B gene
** acts as a chaperone involved in proper folding of collagens
4
Q
Hereditary equine regional dermal asthenia (HERDA) C/S
A
usually seen at 2 years old when broken into saddle– skin tears, or wounds with prolonged healing times
**develop disfiguring scars
-skin is loose and hyperelastic
5
Q
What is the prevalence of Hereditary equine regional dermal asthenia (HERDA) in
Quarter horses?
A
3.5%
**inc prevalence in cutting horses (up to 28%)
**w/in pleasure/working-cow horses (up to 12.8%)
6
Q
Warmblood fragile foal syndrome gene mutation
A
PLOD1 (procollagen lysin, 2-oxglutarate 5- dioxygenase 1) gene
**codes enzyme for collagen biosynthesis
7
Q
Warmblood fragile foal syndrome C/S
A
is af atal defect of connective tissue involving severe skin malformations in enonatal foals
8
Q
Chronic progressive lymphadema is seen in what breeds?
A
draft breeds: clydesdales, belgian drafts and shires
9
Q
chronic progressive lymphadema lesions
A
start at early age
-progressive swelling of legs & development of severe chronic skin changes such as hyperkeratosis & dermal fibrosis with thick skin folds & nodules
-secondary skin infections– contrib to chronic changes
-severe discomfort
10
Q
Junctional epidermalysis bullosa gene mutations
A
- LAMA 3: american saddlebreds
- lamC3– belgian and other drafts
11
Q
Junctional epidermalysis bullosa clinical signs
A
mechanobullous dz: development of ulcers adn bilsters in the skin at pressure points (hocks/stifle) or mucocutaneous junctions (mouth & anus)
oral lesions: premature eruption of teeth & loss of enamel= bleeding mouth
12
Q
Hypotrichosis is a disease of what breeds?
A
curly coated breeds: american bashkir, culry horses and missouri fox trotters
13
Q
hypotrichosis clinical signs
A
alopecia @ birth or develops early during neonatal period
defects in ectodermal structures: teeth, hooves, eyes or seat glands
– normal shedding periods, some permanent loss of main & tail
14
Q
Pemphigous foliaceus describes a group of what disorders?
A
autoimmune vesiculobullous disorders characterized histologically by:
-intraepidermal acantholysis
-intercellular deposition of immunoglobulin
15
Q
What are the clinical lesions primarily recognized in Pemphigous foliaceus?
A
-scaling
-crusting
–>generalized exfoliative dermatitis, ventral or peripheral edema, fever depression
16
Q
What are characteristic histologic findings of Pemphigus foliaceus?
A
-intragranular to subcorneal cleft and vesicle formation assoc with acantholysis
17
Q
Why is recommended to review on slide exam of biopsies in cases of pemphigus foliaceus?
A
certain strains of Trichophyton spp of dermatophytes may also cause acantholysis
**any histology suggestive of pemphigus foliaceus must be stained for fungi
18
Q
What are recommended treatments for pemphigus foliaceus?
A
-immunosuppressive doses of corticosteroids
-prednisolone: 1 mg/kg
-dexamethasone: 0.08-0.1 mg/kg PO q24h, then tapering
-gold salts (historic tx)
-azathioprine: 1-3 mg/kgPO q24-48h
19
Q
Why is oral prednisole preferred to prednisone?
A
–some horses are unable to metabolize prednisone into active metabolite of prednisolone
20
Q
What is the prognosis for horses diagnosed with pemphigus foliaceus?
A
–lifelong administration of steroids required
21
Q
Pemphigus vulgaris is a rare autoimmune skin disease ancedotally reported in horses characterized by:
A
-circulating IgG directed against the epidermal transmembrane protein desmolgein-3
22
Q
What are clinical signs of pemphigus vulgaris?
A
vesicles
ulcerations– @ mucocutaneous & cutaneous areas
23
Q
What is bullous pemphigoid?
A
an autoimmune vesiculobullous and ulcerative disorder that affects the cutaneous basement membrane zone (BMZ)
24
Q
What is the pathophysiology of bullous pemphigoid?
A
complement activaitng anti-BMZ antibodies bind to glycoprotein ag in lamina lucida of BMZ
–collagen activation results in degranulation of mast cells & chemotaxis of neuts &eos
-eosinphils release tissue destructive enzymes with resultant injury to the BMZ, loss of demoepidermal adherence & blister formation
25
Equine bullous pemphigoid is characterized clinically by:
-painful, crusted or ulcerated lesions of skin (face & axilla), mucous membrane and mucocutaneous junctions
26
Besides the skin, bullous pemphigoid lesions can occur where?
GI tract
27
in horses alopecia areata occurs in what areas?
--areas of nonpruritic alopecia
--most common affected i nhorses: mane, tail & face
28
What is seen in biopsy in cases of alopecia areata?
lymphocytic infiltrated surrounding the base of the hair follicle
29
In cases of alopecia areata does hair regrow?
most horses regrow hair, but this. may take up to 2 to 3 years
30
alopecia areata is often mistaken for what other differential?
ringworm
31
What is the definition of atopic dermatitis?
abnormal immunological response to environmental allergen like pollens, barn dust, and molds
32
What is the etiology of atopic dermatitis?
type I (immediate) hypersensitivity response mediated by IgE-- allergen specific IgE
33
What are clinical signs of atopic dermatitis?
-pruritus
-alopecia
-erythema
-urticaria
-papules
34
Confirmation to formulate allergen-specific immunotherapy is based on what diagnostic tests?
-intradermal testing (IDT)
-serum allergy testing
35
with intradermal skin testing, what does a positive reaction mean?
the horse has antibodies ot the allergen that , on intradermal exposure, cause wheals to form
-->does not necessarily mean the horses clin signs are caused by reacting allergen
36
What is the benefit of performing intradermal skin testing?
-hyposensitization
-- should be performed for 12 months to assess success
37
What are treatments recommended in atopic dermatitis?
-corticosteroid (dex, pred)
-antihistamine hydroxyzine pamoate: cetirizine, doxepin, diethylcarbamazine
-essential fatty acids
38
Urticaria is characterized by
transient focal swellings in the skin or mucous membranes (wheals-- areas of dermal edema)
39
Wheals result from:
vasodilation and transudation of fluid from capillaries and small blood vessels
40
What is the immunologic mechanism that causes urticaria?
type I hypersensitivity (IgE)
41
Non-immune mediated urticaria may be induced by:
Type II: cytotoxic, involving antibody and complement
Type III: immune complex
42
Urticaria can be seen in what other diseases?
--pemphigus foliaceus
-dermatophytosis
-vasculitis
43
Milk allergy is urticaria usually seen in cows when?
cows during the drying off period
44
What is the pathogenesis of milk allergy?
-INC intramammary pressure presumably causes milk proteins to gain access to circulation
-induce type 1 hypersenstiivity
45
Milk allergy is seen in what cattle breeds?
Channel Island breeds
46
Diagnosis of Milk allergy is made how?
by observing an edematous swelling at site of intradermal injection of cows milk or milk protein casein diluted 1:1000
47
What are recommended treatments for cattle with milk allergy?
antihistamines
**culling d/t cows are likely to suffer recurrence of milk allergy
48
Erythema multiform is an immunologic skin reaction, what is seen on skin bopsy?
programmed keratinocyte cell death (apoptosis) in prominent change seen on biopsy
49
What are clinical lesions of erythema multiform?
macules, papules, urticarial lesions, vesicular bullous lesions
--target-like lesions
-scaling, crusting, erosions or ulcers
--variable pruritus and pain
50
What are DDx for erythema multiforme?
-urticaria
-amyloidosis
-other nodular papuler diseases
--> drug eruption should be considered
51
What are characteristic histologic lesions of erythema multiforme?
lichenoid pattern with keraitnocyte apoptosis
52
describe the histopathologic changes seen iwth vasculitis
inflammatory changes in the walls of blood vessels
53
in what cases are cutaneous vasculitis seen?
-photoaggravated dermatitis
-drug reactions
-purpura hemmorrhagica
54
What are cutaneous lesions of vasculitis?
crusts
scales
edema
purpura
necrosis
ulceration
55
what are the treatment recommendations for vasculitis?
-corticosteroids: dexamethasone
-reducing UV light exposure
-topical corticosteroids
-pentoxyifylline
--antibiotics-- prone tos econdary bacterial infections
56
Drug eruptions can occur when:
--initial administration as a immunologically mediated hypersensitivity reactions
OR
--repeated exposure to a drug
57
What medications are seen to cause drug eruptions
-antibacterial agents (semisynthetic penicillins & sulfas)
-local anesthetics
-anticonvulsants
-antipyretics (esp phenylbutazone)
58
Drug eruptions can present as a wide variety of cutaneous manifestations including
-urticaria
-angioedema
-diffuse erythema
-papular rashes
-intense pruritus
-sharply demarcated ulcers secondary to vasculitidies
-vesicular & bullous eruptions
-photosensitization
59
When are drug eruptions typically seen?
--cutaneous lesions are typically seen 24 to 48 hours after drug administration
60
define irritant contact dermatitis
cutaneous reaction to an irritating concentration of an offending agent
**chemically damages skin
61
Define allergic contact dermatitis
represents cutaneous reaction in a sensitized animal to nonirritating concen of the offending agent
**delayed type hypersensitivity (type IV)
62
Treatment of contact dermatitis
-symptomatic treatment
-washing the affected region with water
-pentoxifylline
63
What is the causative agent of rain scald, lumpy wool, strawberry foot rot?
-gram-positive , non-acid-fast, branching filamentous, aerobic bacteria
**parallel rows of coccoid zoospores
64
What are the 3 conditions that must be present for Dermatophilus to manifest?
-carrier animal
-moisture
-skin abrasions
65
Mechanical transmission of dermatophilosis can be caused by:
-biting & non-biting flies, ticks and fomites
66
Distribution of dermatophilosis is worldwide, however what areas are predisposed?
areas with increased rainfall
67
Where are lesions caused by dermatophilus congolensis typically seen?
-dorsal surface of animal-- rain scald
-lower extremities-- dew poisoning
**body areas predisposed to infection are areas most susceptible to maceration & trauma
68
Diagnosis of dermatophilosis is made by?
"railroad-track" cocci on impression smears
--bacterial culture or histpathology
--removal of thick crusts, remove hair--> paintbrush lesions
69
What is the recommended treatment of rain scald?
-remove from wet environment
-removal painful crusts, wash with iodophors or lime sulfur
-antibiotics-TMS, oxytet
**make sure to have proper removal of crust lesions, they are important in contagion**
70
define bacterial folliculitis (superficial pyoderma)
inflammation of hair follicles secondary to bacterial infection
71
define furunculosis
follicular infection that breaks through the follicular wall ("boil")
72
define impetigo
bacterial infection that causes subcorneal pustules but does not involve hair follicles
73
Bacterial folliculitis is typically caused by what bacteria?
-coagulase-positive staphylococcus species
--Staph aureus, Staph pseudointermedius
74
What are C/S of folliculitis/furunculosis/impetigo
crusts
epidermal collarettes
encrusted papules
75
what is an uncommon manifestation of staph spp infection of the skin resulting in nodular lesions?
-botryomycosis
***may req sx excision as well as long-term antibiotics
76
What antibiotics are typically used for bacterial skin infections?
systemic:
-TMS
-enrofloxacin
-doxycycline
-ceftiofur sodium
-vancomycin
-aminoglycoside
local: mupirocin ointment 2%, SSD, tris EDTA/4% chlorhexidin
77
Define cellulitis
severe deep, suppurative process in which a poorly defined area of infection tends to dissect through tissue planes
78
What are the major pathogens for cause of cellulitis?
Staph aureus & Staph (pseud)intermedius
79
What are C/S of cellulitis?
-acute swelling
-lameness
**involving one or more limbs
-inc rectal temperature
-INC HR
-laminitis
-poss. sequelae-- osteomyelitis, bacteremia
80
cellulitis treatment
broad-spectrum antibiotics (ie TMS)
NSAIDS
hydrotherapy
support wraps
81
Causative agent of pigeon fever?
Corynebacterium pseudotuberculosis
82
What is a diagnostic that can be performed to help diagnose equine corynebacterium pseudotuberculosis internal abscesses?
synergistic hemolysis inhibition test
83
Does treatment of pigeon fever typically require antibiotics?
Not if abscesses are solitary, not causing pain or fever
84
Digital dermatitis of cattle is a major cause of lameness in cattle, stages of lesions
1st stage: small (~1-2 cm) focal lesions reddened, circumscribed area (strawberry heel warts) that are extremely painful, exudative
2nd stage: larger (2-6cm) ulcerations lesions
3rd stage: healing lesions, rough, encrusted surface, gray in color
4th stage: chronic proliferative lesions, hyperkeratosis, black papilliform projections
5th stage: healing of lesion
85
Washed surfaces of lesions with Digital Dermatitis appearance
-extremely painful
-red & granular
-white-yellow, gray, brown, black papillary areas with red, granular areas
-lesions bleed easily
86
What are differentials for individuals with Digital dermatitis?
interdigital necrobacillosis (foot rot; foul in the foot; interdigital phlegmon)
interdigital hyperplasia (corns, interdigital fibroma)
interdigital dermatitis
traumatic injury with granulation tissue
87
What are differentials for herd problems of lameness localized to the digit?
-digital dermatitis
-interdigital dermatitis
-laminitis
-excessive sole wear from caustic or abrasive flooring
-improper or no hoof trimming
88
Which herds of cattle are predisposed to developing digital dermatitis?
freestall herds-- more commonly affected than stanchion (tie stall) housed cattle or pastured cattle
**dairy cattle
89
Which bacteria is most commonly implicated in digital dermatitis?
Treponema spp spirochetes
90
What are histopathologic criteria to establish a diagnosis of digital dermatitis
-circumscribed plaque of eroded acantholytic epidermis attended by parakeratotic papilllomatous proliferation profusely colonized by spirochete-dominant bacterial flora
-loss of stratum granulosum
-invasion of stratum spinosum by spirochetes
-infiltration of neutrophils, plasma cells, lymphocytes, eosinophils into the dermis
91
treatment of digital dermatitis
-application of topical antibiotics: oxytetracycline, lincomycin
-systemic antibiotics-- PPG, ceftiofur, req milk withholding
-foot baths: 5% formalin, oxytetracycline, lincomycin, copper sulfate, zinc sulfate, sodium hydroxide
91
What are preventative measures for digital dermatitis?
-improve environmental hygiene
-providing dry, comfortable bedding
-improving ventilation
-sanitize --foot trimming equipment, mobile tilt tables, & livestock trailers
92
Interdigital dermatitis is a condition defined as
condition of acute or chronic inflammation confined to the epidermis of the interdigital skin
93
interdigital dermatitis lesions
small circular ulcers in the interdigital epithelium
severe cases: characterized by ulceration, necrosis & underrunning of the hoof horn
-varying degrees of lameness
-moist, white to gray serous exudate
-skin irritation results in hyeprtrophy
-inc growth rate of the axial hoof wall along excessive horn production along axial wall & sole
94
Which digits are most commonly affected with interdigital dermatitis: cattle in tied systems
hind digits are most commonly affected
95
How does interdigital dermatitis differ from interdigital necrobacillosis (foot rot)
infection extends into the dermis, leading to fissure formation, infection of deeper structure if left untreated, & cellulitis if the pastern & fetlock regions
96
Which bacteria commonly causes the virulent foot rot (VRF) in sheep?
D. nodosus-- gram-neg rod-shaped anaeorbic bacterium
97
in sheep interdigital necrobacillosis is characterized by:
inflammation of interdigital skin, resulting in lameness and loss of body condition
--skin appears pink, most, sensitive to touch
--characterized by underrunning of hoof horn leading to separation of hoof from underlying soft tissue
98
The occurrence of interdigital dermatitis is influenced by what?
local climatic conditions-- wet pasture required for transmission
99
What is the recommended time to rest pastures after interdigital dermatitis the outbreak?
-VFR (virulent foot rot) in sheep-- 14 days
-D nodosus cannot survive off host for more than 7 days
100
Papillomas are associated with what virus?
bovine papillomavirus (BPV)
101
Warts in horses are commonly seen on what locations?
-on the face-- more common
102
Congenital warts in horses are termed?
hamartomatous lesions (epidermal nevus)
**not associated with a virus
103
Pseudocowpox is caused by
bovine herpesvirus-2 (BHV-2)
104
Pseudocowpox lesions can predispose to
**mastitis
105
Diagnosis of pseudocowpox
-isolation of the virus-- BHV-2 serum neutralization tester or histologic demonstration of herpesvirus particles
106
Dermatophytosis (ring worm) is caused by
microsporum and trichophyton spp
--refers to infections of the keratinized tissues of the skin
107
Describe ringworm lesions
lesions are circular, superficial or deep, thick crusts, diffuse moth-eaten appearance with desquamation & alopecia, small crust over follicle, hair is lost
-- usually of face, axillary/girth area may spread over the trunk, rump, neck, head & limbs
108
What is the most common and reliable method of diagnosing dermatophytosis?
fungal culture
**direct microscopic exam
109
Dermatophytosis treatment
-50% captan for tack
-lime sulfur
-bleach (1:10)
-shampoos-- containing miconazole, ketoconazole, and/or 3-4 % chlorhexidine
-20% sodium iodide (NaI)
110
Effective control of ringworm in cattle has been achieved in regions implementing what strategies?
-systemic vaccination
111
Sporotrichosis causative agent
-- yeast Sporothrix schenckii-- pathogenic b/c can switch from yeast to mycelial phase (branching, septate hyphae)
**zoonotic potential
112
what is the cause of equine epizootic lymphangitis in East Africa
Histoplasma capsulatum vaar farcimonsum (farcy)
113
Clinical manifestations of lice are most apparent during what season?
winter
114
What are recommended treatment for lice?
ivermectin-- sucking lice
-topical insecticide-- pyremthroids, permethrins, selenium sulfide, imidacloprid, phoxim, ifpronil
115
Tombiculidiasis is caused by larval stages of mites (harvest mites, chiggers), what are the most common species
Eutrombicula alfreddugesi (N. america)
116
What are the C/S of trombiculidiasis?
crusts & papules-- on face, neck and extremities
-variable pruritus
117
Describe the appearance of mites that cause trombiculidiasis
-red-orange larvae in the center of a papule
-- 6 legged larvae with round body
118
Where do psoroptes mites live?
-on surface of epidermis
119
horses with psoroptic mange have what lesions?
-pruritus
-papules, crusts, alopecia seen on the base of the mane, tail, ears & intermandibular rea
120
Describe appearance of psoroptic mites
-round bodies, long segemented pedicles
121
What is the treatment of psoroptic mange?
topical insecticides-- deltamethrin, coumaphos, diazinon, malathion, toxaphene & lime sulfur
**treat contaminated environment
122
Which breed of horses are predisposed to the development of chorioptic mange?
draft horses
123
in horses chorioptic mange can be treated with what?
-lime sulfur
-fipronil-- applied once weekly for at least 1 month
124
Which forms of mange are reportable in the US?
psroptic mange
chorioptic range
125
Demodectic mites usually live where?
in hair follicles and sebaceous and sweat glands
**host specific
126
Demodex caballi is a normal inhabitant of:
-pilosebaceous apparatus of the eyelids and muzzle and may found in skin scrapings of these areas on horses in the absence of skin lesions
127
What are the 3 most common species responsible for culicoides hypersensitivity?
1. Culicoides varipennis
2. Culicoides obsoletus
3. Culicoides nubeculosus
128
which breed of horse is predisposed to the culicoides sensitivity?
Icelandic horses
129
Culicoides hypersensitivity therapy is aimed at insect control, especially what:
1. stabling horses at sunrise and sunset, peak culicoides feeding hours
2. ultrafine setting or screens placed in windows (0 squares to the square inch)
3. fly control, especially keeping horses away from standing water and using permethrin repellants, usually 2% permethrin sprays. Freq spray, must be applied mroe often than label recommendations. have had success with nonpesticide herbal spray, or roll-on
4. Overhead or stall fans (drafts interfere with insects flight)
5. "dresses" that physically obstruct the insects from reaching the skin
6. hyposensitization is controversial; success may vary with hte presence of an adjuvant or the actual antigen used
7. oral prenisolone to manage pruritus
130
Ventral midline dermatitis in horses is caused by what ectoparasites
-onchocerca cervicalis infestation
-black flies (Simuliidae)
131
Screwworm infestation has been eliminated from the United States, through which methods?
release of sterile males-- d/t mating tendency of female fly
**reportable disease
132
What are management strategies to prevent blow fly strike?
**practices that decrease the incidence of wound or skin irritations
- sheep are clipped below the tail and between the hind limbs ("crutched")
-castration, shearing, docking & lambing avoided during the summer season
133
what is a common cause of filarial dermatitis?
cutaenous conchocerciasis
134
the incidence of cutaneous onchocerciasis has been decreased due to
ivermectin for routine deworming
135
Where are O. cervicalis is typically found where?
coiled in the funicular part of the ligamentum nchae, where they produce calcified nodules
136
What are preferential areas of microfilarial localization?
-ventral midline
-lower eyelid
-lateral limbus of the eye
137
cutaneous onchocerciasis is transmitted by what organism?
Culicoides (acts as an intermediate host)
138
What are the differentials for cutaneous onchocerciasis?
- H. irritans
-hypersensitivity reaction to culicoides
-dermatophytosis
-infestation with mange mites
139
What is the treatment for cutaneous onchocerciasis?
ivermectin or moxidectin
140
Cutaneous stephanofilariasis is seen what region of US?
-western & southwestern regions of US
141
Where do stephanofilaria inhabit what area of the skin?
epidermis
142
Stephanofilaria is transmitted by what organism
female horn fly (H. irritans)
143
What are two species of Hypoderma that parasitize cattle and cause warbles?
Hypoderma bovis
Hypoderma lineatum
144
Hypoderma cysts develop around the what larvae?
L1 larvae--> L3 larvae (grubs) that emerge through breathing pore, fall to the ground & pupate
145
How long does it take for hypoderma life cycle to complete?
1 year
146
Economical loss of hypoderma (warbles) infestation in cattle is due to?
-fly worry
-gadding-- stampede behavior
**stampede injury and decreased feeding & milk production
147
What are differentials for hypoderma warbles in horses?
-eosinophilic granuloma (nodualr collagenolytic granuloma, nodular necrobiosis)
-mastocytoma
-sterile nodular paniculitis
-amyloidosis
148
Why does care need to be taken to remove hypoderma larvae in their entirety?
-- because breaking the larvae & rupturing the cyst during removal can result in severe systemic reaction
149
What are medications to administer to prevent migrating hypoderma larvae?
**systemic insecticides only means of eliminating the migrating larvae
-organophosphates
-marcocyclic lactones
150
With systemic medications in the treatment of hypoderma (warbles), what is the recommended timing?
--not to administer systemic insectivides than 8 to 12 weeks before anticipated first appearance of grubs along the back
--northern US-- not recommended from Oct 1st to March 1st; this is when H. bovis larvae are in the esophagus
151
Sheep keds is caused by what organism?
Melophagus ovinus
--wingless fly approximately 6 to 7 mm in diameter with a ticklike appearance
152
The sheep ked Melophagus ovinus has been shown to be a vector for what organisms?
Rickettsia raoultii
Rickettsia slovaca
153
Melophagus ovinus life cycle occurs where in relation to the host?
-- entire life cycle is spent on the host
154
Infestation of sheep keds is more common in what months?
winter months
155
Sheep keds (melophagus ovinus) infestation results in economic loss form what:
-dec dressed carcass weight of lambs
-reduced clean dry weight of fleece, wool staining
-reduced value of sheep skins b/c of nodular defects
156
Treatment of sheep keds (melophagus ovinus)
-- shearing all sheep in affected flock
--two topical applicaitons of malathion, diazinon, or coumpahos 14 to 21 days intervals to kill emerging adults
157
Cutaneous habronemiasis (equine summer sore) is caused by larvae of what flies?
-harbonema microstoma
-Habronema muscae
-Draschia megastoma
158
What are common areas of cutaneous habronemiasis
--natural areas of body moisture: medial canthus of eye, male genitalia, nictitating membrane ("third eyelid") & distal extremities
159
Describe the life cycle of cutaneous habronemiasis?
-H. muscae and De. megastoma develop in the house fly, M domestica and H. microstoma
- L3 larvae are deposited around the horses mouth and swallowed to pass to the stomach where they mature as adults
160
Diagnosis of cutaneous habronemiasis is confirmed by:
-- confirmed by biopsy-- presence of calcified concretions (sulfur granules)
