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Necrolytic acral erythema: a cutaneous marker of viral hepatitis C.

BACKGROUND: Necrolytic acral erythema (NAE) is a distinctive skin lesion that was found to affect the dorsa of the feet of seven patients having active viral hepatitis C. Necrolytic acral erythema occurs in the form of well circumscribed dusky erythematous areas that develop flaccid blisters in their early stages and a hyperkeratotic surface in their chronic form. Microscopically, lesions of NAE are similar to those of other necrolytic erythemas such as necrolytic migratory erythema, pellagra, and zinc deficiency. METHOD: Seven patients with NAE were included in this study. These patients underwent microscopic examination of punch biopsy specimens of the affected skin, abdominal sonography, CT scan of pancreas, and a liver biopsy. Blood samples were obtained for complete blood picture, serum glucose, zinc, amino acids, liver function tests, and markers of hepatitis. RESULTS: All patients with NAE were found to have hepatitis C by ELISA and PCR. CONCLUSIONS: Necrolytic acral erythema is a distinctive type of necrolytic erythemas that was observed to occur almost exclusively with viral hepatitis C. Therefore, it should be considered an important cutaneous marker of hepatitis C, particularly in areas showing a high incidence of this form of hepatitis.

Adult↗

Inhibition of erythema induced by pro-inflammatory esters of 12-deoxyphorbol.

The pro-inflammatory tigliane esters 12-deoxyphorbolphenylacetate (12-DOPPA) and 12-deoxyphorbolphenylacetate-20-acetate (12-DOPPAA) at a dose of 0.1 microgram induced erythema in the mouse ear. Observations of ear redness were made both two and four hours after application. Indomethacin was only partly successful as an antagonist since 10% inhibition of 12-DOPPA and no inhibition of 12-DOPPAA induced erythema was produced four hours after application. The free radical scavengers, phenol, thioanisole and sodium benzoate all produced less than 30% inhibition of 12-DOPPA induced erythema and less than 15% inhibition of 12-DOPPAA, whereas aminopyrine produced 70% and 25% inhibition of 12-DOPPA and 12-DOPPAA respectively. The fact that free radical scavengers (with the exception of aminopyrine) and indomethacin, failed to markedly change the mouse ear reaction to 12-deoxyphorbol esters, indicated that this erythema is not entirely mediated via cyclooxygenase products. Mepyramine and cyproheptadine also failed to inhibit the erythema, whereas hydrocortisone produced a 55% inhibition of the 12-DOPPA and a 20% inhibition of the 12-DOPPAA reaction. The membrane stabilising agents trifluoperazine, promethazine, imipramine and desmethylimipramine were the most successful compounds used in inhibiting both 12-DOPPA and 12-DOPPAA induced erythema. In addition propranolol, which inhibits stimulus activation of phospholipase A2, produced 70% and 55% inhibition of the reaction of mice ears to 12-DOPPA and 12-DOPPAA.

Animals↗

A comparison of erythema efficacy of ultraviolet B irradiation from Philips TL12 and TL01 lamps.

The erythema efficacy of UVB irradiation from Philips TL12 and TL01 lamps has been evaluated and compared. Thirty-seven healthy Thai volunteers were irradiated on the previously unexposed lower back with TL12 and TL01 lamps in doses ranging 100 to 550 mJ/cm2 and 360 to 2020 mJ/cm2, respectively. Erythema was evaluated clinically and measured by a narrow-band spectrophotometer before exposure and 24 h after exposure. The threshold doses of UVB that induced barely perceptible erythema (MEDb) with well-defined border erythema (MEDw) and the steepness of the dose-response curves for erythema (DRAE) were compared. We found that MEDb and MEDw of the TL01 lamps were 4.19 and 4.52 times those of TL12 lamps, which were similar to those calculated from the CIE erythema action spectrum (4.2). However, the DRAE of the two lamps were quite similar. Because the initial dosage of UVB phototherapy is usually given as a percentage of a patient's MED, the initial exposure of TL01-UVB phototherapy should be about 4.2 times that of TL12-UVB.

Adolescent↗

The effects of heating and cooling on ultraviolet radiation-induced erythema and pigmentation in human skin.

BACKGROUND/PURPOSE: As most biochemical systems are affected by temperature, thermal changes before or after ultraviolet (UV) irradiation could influence skin vascular blood flow changes and inflammatory responses. In this study, our aim was to investigate the influence of thermal changes on UV-induced acute skin reactions, namely, erythema and pigmentation. METHODS: Our volunteers consisted of 10 males, with ages ranging from 22 to 24 years and with Fitzpatrick's skin type III or IV. Skin temperatures were changed with a 45 degrees C heating pad or by ice pack application before or after UV irradiation (control, 1 minimal erythema dose (MED), 2 MED) and then changes in erythema and pigmentation were measured by a Minolta Spectrophotometer CM-2002. RESULTS: The present study demonstrates that both heating and cooling increase skin erythema and reduce pigmentation, and that the timing of heating and cooling influences the UV-induced skin reaction. Pre-heating and post-cooling groups showed more UV-induced erythema than the post-heating and pre-cooling groups, respectively. CONCLUSION: Our results indicate that alteration of skin surface temperature could modulate UV-induced erythema and pigmentation responses.

Adult↗

Mutational analysis of superantigen activity responsible for the induction of skin erythema by streptococcal pyrogenic exotoxin C.

Streptococcal pyrogenic exotoxin C (SPEC), when injected intradermally, induces erythema in unsensitized rabbits. In the present study, we examined whether this erythema induction is due to the T-cell stimulatory activity of SPEC as a superantigen. Analysis by using single-residue mutant SPECs indicated that mutant SPECs Y15I, A16E, and Y17I, in which tyrosine 15, alanine 16, and tyrosine 17 were replaced with isoleucine, glutamic acid, and isoleucine, respectively, exhibited significantly reduced mitogenic activity for Vbeta2(+) human T cells in vitro, and Y15I showed as much as a 1, 000-fold reduction. Y15I mutant SPEC, however, retained the ability to bind to major histocompatibility complex class II antigen and to form a homodimer, implying that residue 15 is critically important for the interaction of SPEC with T-cell antigen receptor beta chains. When injected intradermally into normal rabbits, wild-type SPEC induced a characteristic erythema after 3 h in a dose-dependent fashion, which was associated with polymorphonuclear and mononuclear cell infiltration. This erythema formation was found to be severely suppressed by systemic pretreatment with cyclosporin A, suggesting the involvement of host T cells. Y15I mutant SPEC exhibited nearly 1, 000-fold less erythema induction in vivo than wild-type SPEC. Altogether, the present results strongly suggest that erythema induction in rabbits by SPEC is attributable mostly to its T-cell stimulatory activity as a superantigen.

Amino Acid Sequence↗

The UV erythema test as a model to investigate the anti-inflammatory potency of topical preparations--reevaluation and optimization of the method.

BACKGROUND: The ultraviolet (UV) erythema test is one of the most frequently used methods to investigate the anti-inflammatory potency of topical dermatological preparations in vivo. METHODS: The following questions were addressed in four separate studies with healthy persons (skin types 2 and 3): (1) the optimal localization was determined by comparing light scales on the back, buttocks and volar forearms; (2) the optimal UV-B dose was determined by comparing the 1-fold, 1.5-fold and 2-fold minimal erythema doses (MEDs); (3) hydrocortisone and prednicarbate were evaluated as positive controls, and a sample size calculation was performed, and (4) betamethasone valerate and pimecrolimus were tested as further positive controls in the optimized study model. RESULTS: The back proved to be the best localization for the UV erythema test. It showed a good correlation between the light scale and the test areas. The 1.5-fold MED was the best irradiation dose. In contrast to prednicarbate and betamethasone valerate, hydrocortisone was a rather weak positive control. However, when the sample size was > or = 40 subjects, significant results were also obtained with hydrocortisone. Pimecrolimus was not effective in the UV erythema test. CONCLUSIONS: The UV erythema test should be performed on the back with at least 40 subjects using the 1.5-fold MED. It may be useful to include a potent corticosteroid, such as prednicarbate or betamethasone valerate, in addition to hydrocortisone. The UV erythema test seems to be suitable only for substances with corticosteroid-like effects, since in this test model the calcineurin inhibitor pimecrolimus was not effective.

Administration, Topical↗

Anti-SSA/Ro antibody as a risk factor for fluorouracil-induced drug eruptions showing acral erythema and discoid-lupus-erythematosus-like lesions.

BACKGROUND: It is well known that fluorouracil (FU) agents frequently induce discoid-lupus-erythematosus (DLE)-like eruptions and acral erythema in Japan. However, the etiology of these drug eruptions caused by FU agents has not been clarified yet. OBJECTIVE: To determine if the existence of anti-SSA/Ro antibody may be a risk factor for FU-agent-induced DLE-like eruptions and acral erythema. PATIENTS AND METHODS: Six patients with FU-agent-induced drug eruptions showing DLE-like lesions and acral erythema were enrolled in this study. The titers of anti-SSA/Ro antibody in the sera and the histopathology of the skin lesions were examined. RESULTS: Biopsy specimens from DLE-like eruptions and all 5 examined acral erythema cases showed lichenoid change of the basal keratinocytes. Direct immunofluorescence studies revealed deposition of immunoglobulins along the basement membrane zone in the lesions of both DLE-like eruptions and acral erythema. Further, all 6 cases had high titers of serum anti-SSA/Ro antibody, which did not decline within 6 months after cessation of the causative drug. CONCLUSION: We propose that anti-SSA/Ro antibody may be a risk factor for FU-agent-induced drug eruptions showing acral erythema and DLE-like eruptions.

Aged↗

Evaluation of skin erythema by use of chromametry and image analysis of digital photographs after intradermal administration of histamine in dogs.

OBJECTIVE: To investigate whether the degree of erythema during an induced erythematous reaction, the histamine skin test reaction, can be assessed objectively by use of chromametry and image analysis of digital photographs. ANIMALS: 9 pet dogs (6 Golden Retrievers and 3 yellow Labrador Retrievers). PROCEDURE: Histamine phosphate was injected intradermally, and erythema of the wheal reaction was evaluated during the hour that followed. This was done by use of clinical scores, chromametry, and image analysis of digital photographs. Method reproducibility was tested for visual evaluation of printouts of digital photographs and for image analysis of the same photographs. RESULTS: The coefficient of variation of the technically derived erythema values was < 10%. The reproducibility of image analysis was high and the range of agreement between observers narrow. Using chromametry, it was not possible to differentiate between various degrees of erythema intensity as visually perceived. In contrast, use of image analysis of digital photographs enabled discrimination of slight erythema from moderate and marked erythema. The dynamics of reaction measured by chromametry followed the clinical observation. CONCLUSIONS AND CLINICAL RELEVANCE: Chromametric values are comparable to those obtained by visual inspection. As the result of standardized conditions, chromametry is preferred over digital photography.

Animals↗

Azithromycin compared with amoxicillin in the treatment of erythema migrans. A double-blind, randomized, controlled trial.

OBJECTIVE: To determine whether azithromycin or amoxicillin is more efficacious for the treatment of erythema migrans skin lesions, which are characteristic of Lyme disease. DESIGN: Randomized, double-blind, double-dummy, multicenter study. Acute manifestations and sequelae were assessed using a standardized format. Baseline clinical characteristics and response were correlated with serologic results. Patients were followed for 180 days. SETTING: 12 outpatient centers in eight states. PATIENTS: 246 adult patients with erythema migrans lesions at least 5 cm in diameter were enrolled and were stratified by the presence of flu-like symptoms (such as fever, chills, headache, malaise, fatigue, arthralgias, and myalgias) before randomization. INTERVENTION: Oral treatment with either amoxicillin, 500 mg three times daily for 20 days, or azithromycin, 500 mg once daily for 7 days. Patients who received azithromycin also received a dummy placebo so that the dosing schedules were identical. RESULTS: Of 217 evaluable patients, those treated with amoxicillin were significantly more likely than those treated with azithromycin to achieve complete resolution of disease at day 20, the end of therapy (88% compared with 76%; P=0.024). More azithromycin recipients (16%) than amoxicillin recipients (4%) had relapse (P=0.005). A partial response at day 20 was highly predictive of relapse (27% of partial responders had relapse compared with 6% of complete responders; P<0.001). For patients treated with azithromycin, development of an antibody response increased the possibility of achieving a complete response (81% of seropositive patients achieved a complete response compared with 60% of seronegative patients; P=0.043). Patients with multiple erythema migrans lesions were more likely than patients with single erythema migrans lesions (P<0.001) to have a positive antibody titer at baseline (63% compared with 17% for IgM; 39% compared with 16% for IgG). Fifty-seven percent of patients who had relapse were seronegative at the time of relapse. CONCLUSIONS: A 20-day course of amoxicillin was found to be an effective regimen for erythema migrans. Most patients were seronegative for Borrelia burgdorferi at the time of presentation with erythema migrans (65%) and at the time of relapse (57%).

Adult↗

Erythema migrans and serodiagnosis by enzyme immunoassay and immunoblot with three borrelia species.

There is wide divergence of opinion between physicians regarding the use of serological measures for the diagnosis and treatment of erythema migrans, the hallmark of Lyme borreliosis. We studied the outcome of an enzyme immunoassay and immunoblot (Western blot) used on the sera of patients who had suffered tick bite and erythema migrans, and had been subsequently treated with various antibiotics. Ninety-nine consecutive patients presenting with erythema migrans after tick bite were prospectively recruited at the outpatient department of two Vienna City hospitals and at the consultation office for Lyme borreliosis of the Institute of Hygiene. University Vienna. Blood samples were taken before antibiotic treatment and 3 and 6 months thereafter. Blood samples from 100 blood donors served as controls. Antibodies against Borrelia burgdorferi sensu lato were determined by enzyme immunoassay (IgG and IgM EIA) and by IgG immunoblot. The latter was performed with isolates of B. alzelii (H2) B. burgdorferi sensu stricto (Le) and B. garinii (W) from Austrian patients. The 4 interpretation criteria for immunoblot results were: A (3 bands out of 8), B (2 bands out of 9), C and D (1 band out of 6). In all patients, the erythema resolved within the treatment period. No complications secondary to the borrelia infection were registered. After treatment there was no significant change in titre, nor was there a difference in the immunoblot pattern between the first, second and third serum samples. Serum antibodies to B. burgdorferi were positive by EIA in 22.9% (IgG) and 2.5% (IgM). Immunoblot results offered by borrelia species and by the interpretation criteria, ranging between 8.3% (criterion A, strain Le) and 44.2% (criterion D, strain H2). By EIA, control samples were IgG and IgM positive in 5% and 1%, respectively. Positive immunoblot results with strain H2 were found in 9%, 13%, 18%, and 20% by the criteria A through D respectively. After antibiotic treatment of erythema migrans the immunological response appears to be abrogated. Thus, serological results are not supportive for the diagnosis of erythema migrans, not will they retrospectively prove successful antibiotic treatment of borrelia infection.

Adolescent↗

Testing the validity of erythema detection algorithms.

Dermatology has quantified skin color for monitoring progress of treatments. The most common and effective means of erythema detection is visual inspection of the skin. However, for people with darkly pigmented skin, erythema can be masked by melanin. Tissue Reflectance Spectroscopy (TRS) is a noninvasive method of quantifying skin color. Most commonly, TRS quantifies erythema caused by cosmetics, topical ointments, UV light, or other irritants. Recently, TRS has been used to characterize the presence of erythema due to reactive hyperemia or Stage I pressure ulcers. The objective of this study was to compare the reliability and validity of erythema detection algorithms by determining their sensitivity and specificity. Two algorithms, Diffey and Helen Hayes Hospital (HHH), had sensitivity exceeding 85% and specificity exceeding 75%, but most algorithms demonstrated adequate validity across all subjects. The validity of the HHH algorithm did not change with the skin pigmentation of the subject. The results of this comparison will be useful to researchers interested in using TRS to detect erythema in people with different skin pigment levels.

Algorithms↗

Analysis of localized erythema using clinical indicators and spectroscopy.

Localized erythema is regularly used as an indicator of post-ischemic events, including reactive hyperemia and Stage I pressure ulcers. The National Pressure Ulcer Advisory Panel definition of a Stage I ulcer includes both visual and nonvisual indicators in part to improve identification in darkly pigmented skin. A prospective, repeated-measures design was used to collect information on pressure-induced erythema that includes reactive hyperemia and Stage I pressure ulcers with an emphasis on distinguishing indicators in light and dark skin The relationships among clinical indicators (skin assessments) and results from tissue reflectance spectroscopy, as well as the clinical utility of spectroscopy for discerning tissue blanching status, were examined in a convenience sample of 76 inpatients and outpatients (95 test/control site pairs). Chi-square analysis and generalized logistic models were used to identify relationships and distinguishing characteristics of erythema. Analysis of variance was used to analyze blanching using spectroscopy. Nonblanching sites were more likely to be persistent erythema (c2=5.3; P = 0.021) but exhibited no relationships to temperature, tissue resilience, or disability. Erythema in subjects with dark skin was more likely to be nonblanching and have poor resilience. Spectrographic analysis of blanching found significant differences across skin pigmentation (P = 0.0001) and blanching status (P = 0.019). These results reinforce the belief that dark skin must be assessed differently than light skin and indicate that clinicians should use persistence of erythema rather than blanching status to judge incipient pressure ulcers. These results validate the use of visual and nonvisual indicators included in the National Pressure Ulcer Advisory Panel Stage I pressure ulcer definition.

Adult↗

[Time-dose relationship of erythema in high energy photon irradiation therapy].

Skin doses of 100 patients who were treated with high energy ionizing irradiation during conventional irradiation therapy were measured by thermoluminescence dosimeter (TLD). In 87 of the 100 patients, acute hyperemic change of the skin (erythema) of the irradiated region was observed. In the other 13 patients, alopecia of the scalp was observed. The following conclusions were reached. 1) The time-dose relationship was linear when erythema tolerance was used as an index, but not when alopecia was used. 2) The tolerance dose for erythema was lower than previously reported. The slope of the isoeffect curve on the log-log plot of total absorbed skin dose against total number of days after the first irradiation was 0.68 when erythema was used as an index. This number is larger than previously reported results. We considered that erythema is significantly influenced by fraction size and that hyperfractionation is a promising method of irradiation, especially in Japan. 3) Combined use of chemotherapeutic agents, such as 5-Fu, accelerated erythema. The slope of combined treatment was 0.86. Observing acute hyperemic change of skin is considered to be a useful method of investigating the combined effects of chemotherapeutic agents on irradiation.

Dose-Response Relationship, Radiation↗

[Pigmented erythema: a marker of alcoholism].

The aim of this paper is to describe the association between chronic alcoholism and pigmented erythema in the lower limbs. 489 patients were prospectively registered for this study; a significant association was observed between chronic alcoholism and pigmented erythema (prevalence 41,95 in alcoholics and 14.29 in nonalcoholics. x2 = 47.57; p less than 0.0001; OR = 4.274, confidence interval (CI) = 6.49-2.81); being more evident in patients under 60 years old (40% in alcoholics and 5.94 in non-alcoholics. x2 = 37.36; p less than 0.0001; OR = 9,21; IC = 4.29-19.77). Alcoholics with erythema tended to be the older ones, however, at the same time, they were younger than the non-alcoholic patients with erythema. Erythema was associated to the period time of ethanol addiction. Thus, we concluded that pigmented erythema can be considered a new alcoholism marker.

Adolescent↗

Erythema multiforme.

In summary, the diagnosis of erythema multiforme is appropriate for a self-limiting or episodic cutaneous or mucocutaneous illness with skin lesions morphologically and histologically compatible. With typical erythema multiforme minor, characterized by classic skin lesions with or without oral erosions, most patients' disease is associated with recurrent herpes simplex infections. This is particularly true with recurrent erythema multiforme. Symptomatic conservative care, antibiotic treatment for purulent secondarily infected oral lesions, and avoidance of systemic steroids are appropriate therapeutic guidelines. The more serious syndrome, erythema multiforme major, or Stevens-Johnson syndrome, is characterized by skin lesions that are somewhat atypical and different from those of erythema multiforme minor in association with erosions on multiple mucosal surfaces. Drugs and mycoplasmal infections are important precipitating factors for erythema multiforme major. Hospitalization and laboratory tests are often required because of the severity of the illness and the occasional damage to other organ systems. Conservative, symptomatic care, withdrawal of any drug that may have caused the illness, treatment of any mycoplasmal infection, and antibiotic therapy for purulent secondarily infected lesions are worthwhile therapeutic measures. Early treatment with systemic steroids may be helpful in preventing further damage, and the risks and potential benefits of such therapy must be evaluated on an individual basis.

Adrenal Cortex Hormones↗

[Clinical and etiological aspects of erythema multiforme. A propos of 40 cases].

The authors analyse 40 cases of erythema multiforme (including twenty children under fifteen) seen over a five-year period at the Sick Children's Hospital in Bordeaux, Bullous erythematous target lesions of the skin were associated, in most cases, with pluri-orificial ulcerations on the mucous membranes and, less frequently, with more or less severe systemic or visceral symptoms. Borderline cases were observed, associating features of erythema multiforme simplex and of Lyell disease with variable degrees of dermoepidermal blistering and epidermal necrosis. Infection (32.5% of cases) is a more common etiology in children than in adults; the main pathogens are herpes simplex virus, vaccinia pox virus, and Mycoplasma pneumoniae. Drug-induced forms (37% of cases), which are more often seen in adults than in children, are usually due to sulfonamides or antiinflammatory agents. In 30% of cases, no etiology could be demonstrated. Attention is drawn to the frequency of facial vespertilial erythema, as well as the possible occurrence of severe conjunctival sequellae. The connections between erythema multiforme, fixed drug-induced eruptions, and Lyell disease are discussed: only the last, which implies dermoepidermal cleavage, can be categorized with erythema multiforme. The staphylococcal scalded skin syndrome, in which the epidermolysin of Staphylococcus aureus type II 71 is responsible for a superficial cleavage, proceeds from entirely different mechanisms and should be regarded as totally distinct from erythema multiforme.

Adolescent↗

[Effects of anti-inflammatory drugs on the arachidonic acid induced erythema in guinea pigs (author's transl)].

The inhibitory effects of anti-inflammatory drugs on th erythema induced by arachidonic acid in guinea pigs were studied. Values of ED50 (mg/kg, p.o.) were; diclofenac sodium (19.9), indomethacin (28.1), naproxen (52.4), phenylbutazone (67.1), ibuprofen (81.3), aspirin (92.6). These drugs, however, were ineffective on the erythema induced by prostaglandin E2. Basic nonsteroidal and steroidal anti-inflammatory drugs and anti-oxidants were negative in the inhibition of arachidonic acid-induced erythema. Cyproheptadine as an anti-histamine and -serotonin agent and morphine as a CNS acting agent were also negative. Erythema did not occur following treatment with linoleic acid, linolenic acid and gamma-linolenic acid. Bishomo-gamma-linolenic acid-induced erythema was inhibited by diclofenac sodium. The inhibition of acidic nonsteroidal anti-inflammatory drugs in this system seemed to be the result of a block of the enzymatic conversion of arachidonic acid to prostaglandins. The arachidonic acid-induced erythema in guinea pigs can serve as a new animal model for evaluating prostaglandins biosynthesis inhibitors such as anti-inflammatory drugs.

Animals↗

Reduction of erythema in hairless guinea pigs after cutaneous sulfur mustard vapor exposure by pretreatment with niacinamide, promethazine and indomethacin.

Erythema is the initial symptom that occurs after sulfur mustard (HD) cutaneous exposure. The time course of HD-induced erythema is similar to that observed after UV irradiation, which can be reduced by indomethacin. Sulfur mustard lethality is decreased by using promethazine, which is an antihistamine. Niacinamide can reduce microvesication after HD vapor exposure in hairless guinea pig (HGP) skin. The present study examines the effect of the combined administration of niacinamide, indomethacin and promethazine used alone or in all possible combinations on the degree of erythema and histopathologic skin damage after HD exposure in HGP. Niacinamide (750 mg kg-1, i.p.), promethazine (12.5 mg kg-1, i.m.) or indomethacin (4 mg kg-1, p.o.) used singly or in combination was given as a 30-min pretreatment before an 8-min HD vapor cup skin exposure. Using a combination pretreatment of niacinamide, promethazine and indomethacin, erythema was reduced at 4 (91%) and 6 (55%) h, but not 24 h after HD. The incidence of histopathological skin changes (microvesicles, follicular involvement, epidermal necrosis, intracellular edema and pustular epidermatitis) 24 h after HD was not reduced. This study indicates that HD-induced erythema may result from several different mechanisms, including inflammation, histamine release and DNA damage. It is suggested that two phases of inflammation may occur: an early phase sensitive to antihistamines and non-steroidal antiinflammatory drugs and a late phase of extensive cell damage that was not sensitive to these drug pretreatments.

Animals↗