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PubMed2002

The role of histamine H(1) receptors in late-phase reaction of allergic conjunctivitis.

The role of histamine H(1) receptors in the late-phase reaction of allergic conjunctivitis was studied using histamine H(1) receptor-deficient mice. To clarify the eosinophil infiltration, which is a reliable indicator of late-phase reaction, eosinophil peroxidase activity in the conjunctiva was measured. Mice were actively immunized with ovalbumin, and conjunctivitis was induced by topical instillation of ovalbumin. A significantly high eosinophil peroxidase level in the conjunctiva was observed in sensitized wild-type mice, whereas sensitized histamine H(1) receptor-deficient mice showed no significant increase in the conjunctival eosinophil peroxidase level. In addition, the elevation of eosinophil peroxidase level observed in sensitized wild-type mice was significantly antagonized by pretreatment with anti-P-selectin antibody. From these findings, it was concluded that eosinophil infiltration into the conjunctival tissue in late-phase reaction of allergic conjunctivitis is mediated by P-selectin stored in endothelial cells via histamine H(1) receptors.

Animals↗
PubMedDate not supplied

Acute conjunctivitis associated with biofilm formation on a punctal plug.

BACKGROUND: Punctal plugs are used for the treatment of tear-deficient type dry eye. We recently examined a case of acute conjunctivitis associated with bacterial biofilm formation on a punctal plug. CASE: A 63-year-old woman diagnosed as having tear-deficient type dry eye came to our hospital with a complaint of soreness in her right eye. Punctal plugs had been inserted into this eye 5 1/2 months previously. On the day of her visit, she presented with acute conjunctivitis. OBSERVATIONS: In biomicroscopical examination, the top of the punctal plug was seen to be covered with a whitish soft material. Microbiological analysis performed on a part of this material was positive for Staphylococcus haemolyticus and Candida tropicalis. Scanning electron microscopy of the removed punctal plug revealed widespread bacterial colonization embedded within an extensive extracellular matrix. Treatment consisted of the replacement of the plug, and administration of a combination of antibacterial eyedrops and preservative-free artificial solution. As a result, the acute conjunctivitis cleared up within 1 month. CONCLUSIONS: This case suggests that a punctal plug poses a potential risk of causing the formation of bacterial biofilm. In such a case, replacement of the plug and/or removal of the accumulated materials should be considered.

Acute Disease↗
PubMedDate not supplied

Prevalence of Chlamydia trachomatis pooled serotypes BDE and FGK in children with chronic follicular conjunctivitis.

PURPOSE: To evaluate type-specific antichlamydial antibody IgG in children with chronic follicular conjunctivitis. METHODS: A total of 90 serum samples from juvenile patients with chronic follicular conjunctivitis were collected in the Southeastern Anatolian region of Turkey where trachoma is still endemic. These samples were investigated regarding Chlamydia trachomatis pooled serotype-specific IgG by using the micro-immunofluorescence test. A titer of 1/32 or higher was considered positive. RESULTS: Specific IgG seropositivity to Chlamydia trachomatis titer was found in 33 (36.1%) of the 90 subjects. A higher titer was observed frequently in the serotypes pooled in BDE (21 subjects), CHIJ (10 subjects), and FGK (2 subjects), respectively. CONCLUSIONS: The presence of antichlamydial antibodies in blood should always be interpreted in accordance with the history of the patient, the clinical picture, and the course of the disease. In the diagnosis of Chlamydia trachomatis infections in a patient with chronic follicular conjunctivitis, not only genus-specific antibodies but also the presence of the subspeciespecific antibodies should be investigated.

Antibodies, Bacterial↗
PubMed1984

Efficacy of topical antibiotic therapy in acute conjunctivitis in children.

We studied 102 children aged 1 month to 18 years in a randomized, double-blind trial designed to determine both the natural history of bacterial conjunctivitis and whether topical antibiotic therapy is beneficial. Affected eyes were treated four times a day for 7 days with drug (polymyxin-bacitracin ophthalmic ointment) or placebo. Eighty-four patients had proved bacterial conjunctivitis (Haemophilus influenzae 61, Streptococcus pneumoniae 22, both one); 66 of these received only topical therapy. By 3 to 5 days, 21 of 34 (62%) patients receiving topical antibiotic were clinically cured, whereas only nine of 32 (28%) patients given placebo were cured (P less than 0.02). By 8 to 10 days, 31 (91%) of the patients given antibiotic and 23 (72%) of the placebo group were cured (P = NS). The bacterial pathogen was eradicated by day 3 to 5 in 71% and by day 8 to 10 in 79% of patients given antibiotic, compared to 19% and 31% of the placebo group (P less than 0.001). Acute bacterial conjunctivitis is a self-limited disease, but topical antibiotic therapy with polymyxin-bacitracin shortens the duration of clinical disease and enhances eradication of the causative organism from the conjunctiva.

Acute Disease↗
PubMed1996

Interaction between nitric oxide and prostaglandin synthesis in the acute phase of allergic conjunctivitis.

Both nitric oxide and prostaglandins induce vasodilatation which is an important feature of local inflammation. The purpose of the study described here was to investigate a possible interaction between these two types of mediators in an experimental model of allergic conjunctivitis. A conjunctival allergic reaction was induced with antigen in sensitized guinea pigs. Conjunctival vascular permeability changes were evaluated with the prophylactic use of an inhibitor of nitric oxide synthase (L-NAME) and a cycloxygenase inhibitor (indomethacin). To study a possible interaction between nitric oxide and prostaglandin synthesis in the acute phase of allergic conjunctivitis, the levels of nitrite and PGE2 were determined in lavage fluid. The prophylactic use of L-NAME on the formation of conjunctival edema in response to topical PGD2 administration was studied by measurement of albumin levels in lavage fluid. Both nitric oxide and PGE2 are synthesized in response to antigen provocation and after histamine administration. Nitric oxide and PGE2 are produced simultaneously in the conjunctiva and they showed identical synthesis profiles in response to antigen provocation. Pretreatment with L-NAME inhibited the synthesis of PGE2 whereas exogenous administration of nitric oxide increased the level of PGE2 in lavage fluid. Prophylactic treatment with L-NAME significantly inhibited the PGD2 induced albumin extravasation. Nitric oxide seems to play an important role in the acute phase of allergic conjunctivitis it may stimulate PGE2 production and acts as a secondary mediator in PGD2 and histamine induced conjunctival edema.

Administration, Topical↗
PubMed1998

A randomized, double-masked, placebo-controlled parallel study of 0.2% loteprednol etabonate in patients with seasonal allergic conjunctivitis.

BACKGROUND: Loteprednol etabonate is a site-active corticosteroid with efficacy and safety in treating ocular inflammation at the 0.5% concentration. Evidence from dose-response studies suggested that the 0.2% concentration might be effective in treating ocular allergy. OBJECTIVES: The objective of this study was to evaluate the effects of 0.2% loteprednol etabonate in reducing the signs and symptoms of seasonal allergic conjunctivitis. METHODS: This was a randomized, double-masked, placebo-controlled, parallel-group multicenter study. Patients with signs and symptoms of environmental seasonal allergic conjunctivitis received either loteprednol etabonate or placebo bilaterally four times daily for 42 days. RESULTS: Enrolled were 133 patients (66 receiving loteprednol etahonate; 67 receiving placebo). A reduction in severity was seen in both loteprednol etabonate and placebo groups for bulbar conjunctival injection (1.3 vs 0.9 units on a 0 to 3 scale) and itching (3.5 vs 3.1 units on a 0 to 4 scale) over the first 2 weeks. The treatment effect was -0.5 and -0.6 units in favor of loteprednol etabonate (P < .001). Resolution (the proportion of patients with the sign or symptom no longer present) at visit 4 (day 14) strongly favored loteprednol etabonate-treated patients over placebo-treated patients (31% and 9%, and 54% and 38%, for injection and itching, respectively). Both treatments were well tolerated. No patients in either treatment group (0 for loteprednol etabonate and 0 for vehicle) had an elevation of intraocular pressure of 10 mm Hg or greater during the 6 weeks of treatment. CONCLUSIONS: Loteprenol etabonate (0.2%) was more effective than placebo in the treatment of seasonal allergic conjunctivitis. Loteprednol etabonate (0.2%) had a safety profile comparable to placebo during this 6-week trial.

Adult↗
PubMed2002

Effect of airborne allergens on emergency visits by children for conjunctivitis and rhinitis.

The effect of fungal spores and pollen grains on morbidity from childhood conjunctivitis and rhinitis is mostly unknown. We therefore studied the association between daily concentrations of these airborne allergens and daily emergency visits to a children hospital between 1993 and 1997. An increase of 551 basidiomycetes spores per m(3), or of 72 ragweed grains per m(3), was associated with an increase of about 10% in visits for conjunctivitis and rhinitis (p<0.01). Our results suggest that conjunctivitis and rhinitis could be caused by fungal spores and pollens in the air.

Air Pollutants↗
PubMed2002

A comparison of the efficacy and tolerability of olopatadine hydrochloride 0.1% ophthalmic solution and cromolyn sodium 2% ophthalmic solution in seasonal allergic conjunctivitis.

BACKGROUND: Treatments for allergic conjunctivitis have various mechanisms of action. Cromolyn sodium stabilizes conjunctival mast cells by preventing calcium influx across the cell membrane, whereas olopatadine hydrochloride is both an antihistamine and a mast cell stabilizer. OBJECTIVE: This study compared the efficacy and tolerability of olopatadine and cromolyn in controlling the ocular signs and symptoms of seasonal allergic conjunctivitis. METHODS: This was a multicenter, randomized, double-masked, parallel-group trial. One group instilled olopatadine 0.1% ophthalmic solution and placebo BID, and the other instilled cromolyn 2% ophthalmic solution QID, both for 6 weeks. The formulation of cromolyn used in this study is currently available only in Europe and Australia. RESULTS: The intent-to-treat efficacy and safety analyses included 185 patients, 91 in the olopatadine group and 94 in the cromolyn group. At 30 minutes after the first instillation, respective decreases of approximately 30% and approximately 20% were reported in self-rated ocular itching and redness with both treatments; by 4 hours, itching had decreased by approximately 38% in both groups. Differences between treatments were not statistically significant. At 4 hours, redness had decreased by approximately 38% and approximately 26% in the respective treatment groups. By day 42, both treatments had produced significant reductions from baseline in ocular signs and symptoms; however, the reductions in itching and redness were significantly greater with olopatadine compared with cromolyn (both variables, P < 0.05). The difference in physicians' impression of overall improvement on days 30 and 42 significantly favored olopatadine over cromolyn (both days, P < 0.05). Most patients (62.2%) had reacted positively to grass pollen at baseline. The regression slopes correlating itching and redness with pollen count were 5 times lower for olopatadine compared with cromolyn (P = 0.002 and P = 0.016, respectively), indicating that olopatadine's efficacy increased as the pollen count increased. CONCLUSIONS: Six weeks' instillation of olopatadine 0.19% ophthalmic solution BID had a significantly greater effect on the ocular signs and symptoms of allergic conjunctivitis compared with 6 weeks' instillation of cromolyn 2% ophthalmic solution QID. Both treatments were well tolerated by patients in all age groups; however, olopatadine appeared to have better local tolerability in children aged <11 years.

Adolescent↗
PubMed2000

Evaluation of the onset and duration of effect of azelastine eye drops (0.05%) versus placebo in patients with allergic conjunctivitis using an allergen challenge model.

OBJECTIVE: The trial evaluated the effectiveness of the investigational antihistaminic and antiallergic compound Azelastine Eye Drops (AZE) in the treatment of allergic conjunctivitis using an allergen challenge model. DESIGN: Randomized, double-blind, placebo-controlled, paired-eye study. PARTICIPANTS: Adults with a history of allergic conjunctivitis (>/=2 years) who were asymptomatic throughout the trial, had a positive skin test (cat dander, grass, or ragweed pollen within the last year), and had a positive conjunctival reaction (score 2+ or more for itching and redness in both eyes on a 0-4 scale) during two separate conjunctival provocation tests (CPT) before randomization. METHODS: Eighty patients underwent a 2-week screening period (visits 1 and 2) that included a CPT during visit 1 to establish the allergen threshold dose and a second confirmatory CPT performed at visit 2. Eye symptom assessments for itching (evaluated by patient) and conjunctival redness (evaluated by physician) were performed 5 and 10 minutes after CPT using a 5-point scale (from 0 = none to 4+ = severe). Qualified patients were randomized to receive one drop of AZE (0.015 mg of azelastine hydrochloride) in one eye and one drop of placebo in the other eye 20 minutes before CPT at visit 3 (onset) and 8 or 10 hours before CPT at visit 4 (duration). MAIN OUTCOME MEASURES: Individual severity scores for itching (evaluated by patient) and conjunctival redness (evaluated by physician) for each eye at 3, 5, and 10 minutes after CPT at visits 3 and 4 using a 5-point scale (0 = none to 4+ = very severe). RESULTS: Each of the 80 randomized patients completed the trial. Mean itching and conjunctival redness scores at visit 3 (onset) were significantly lower (P: < 0.001) in the AZE-treated eyes than in the placebo-treated eyes. At visit 4 (duration), mean itching and conjunctival redness scores (P: </= 0.003) for the 8-hour group and mean itching scores (P: </= 0.001) for the 10-hour group were significantly lower in the AZE-treated eyes than in the placebo-treated eyes. Significant differences in mean tearing and chemosis severity scores were also seen at visit 3 (onset) and visit 4 (duration) in the AZE-treated eyes when compared with the placebo-treated eyes. Treatment with AZE was well tolerated. CONCLUSIONS: Therapy of experimentally induced allergic conjunctivitis with AZE was highly effective, with an onset of action seen within 3 minutes and a duration of effect of at least 8 to 10 hours.

Adolescent↗
PubMed2000

Effect of eye rubbing on signs and symptoms of allergic conjunctivitis in cat-sensitive individuals.

OBJECTIVE: To evaluate the effect of eye rubbing on signs and symptoms of allergic conjunctivitis in cat-sensitive individuals. DESIGN: Two prospective, nonrandomized comparative studies. PARTICIPANTS: Thirteen patients in the first study and 20 patients in the second study with a documented history of acute allergic conjunctivitis induced by exposure to cats were enrolled. INTERVENTION: In the first trial, all patients had one eye rubbed 15 times by the investigator without exposure to airborne allergens. Both eyes were evaluated after 5, 15, 30, and 60 minutes using subject questionnaires and slit-lamp examination. At least 1 week later, each patient was exposed to cat dander for 75 minutes; 15 minutes after entering the cat room, each patient had one eye rubbed 15 times by the examiner. Subjects' eyes were then evaluated using questionnaires and slit-lamp examination. In the second trial, the visits were identical to the first trial, except that the rubbed eye in each visit was rubbed 20 times and with more force, and that patients wore masks during exposure to cat dander. MAIN OUTCOME MEASURES: In both studies, the difference between patients' rubbed and nonrubbed eyes with respect to ocular itching, chemosis, and hyperemia was noted 5, 15, 30, and 60 minutes after controlled eye rubbing. RESULTS: Without exposure to the cat room, rubbed eyes exhibited increased itching at 5 minutes in both studies and at 15 minutes in the second study (P < 0.05), increased chemosis at 5 and 15 minutes in the second study (P < 0.05), and increased hyperemia at 5 minutes in the second study (P < 0.05) compared with nonrubbed eyes. During exposure to cat dander, rubbed eyes consistently exhibited increased itching at 5, 15, and 30 minutes in the first and second study as well as at 60 minutes in the second study compared with nonrubbed eyes. Furthermore, during exposure to cat dander, rubbed eyes consistently exhibited increased chemosis at 5 and 15 minutes (P < 0.05) and increased hyperemia at 5, 15, and 30 minutes (P < 0.05) in the second study compared with nonrubbed eyes. CONCLUSIONS: Firm eye rubbing causes a mild and transient increase in ocular itching, chemosis, and hyperemia. However, after exposure to cat allergens in cat-sensitive individuals, the effects of eye rubbing are longer and more dramatic. Eye rubbing may play a role in ocular signs and symptoms of allergic conjunctivitis in cat-sensitive individuals, especially after exposure to cat dander.

Acute Disease↗
PubMed1978

Giant papillary conjunctivitis induced by hard or soft contact lens wear: quantitative histology.

Both hard and soft lens wearers develop a syndrome of decreased tolerance, increased mucus, mild itching, and giant papillary excrescences in the upper tarsal conjunctiva that resemble a varnal conjunctivitis. In the fully developed syndrome, the upper tarsal plate has an increase in stringy mucus and is covered by large papillae crowded together. The syndrome develops after months to years of otherwise successful lens wear and occurs in users of all types of soft and hard lenses. Histologic examination of tissues from 55 patients with well-developed giant papillary conjunctivitis compared with tissue from 15 normal people showed three findings characteristic of the syndrome: (1) mast cells in the epithelium, (2) eosinophils in the epithelium and substantia propria, and (3) basophils in the epithelium and substantia propria. Plasma cells and lymphocytes per cubic millimeter were not increased in detailed counts of 15 patients and 15 normal individuals. It is proposed that the number of plasma cells and lymphocytes cannot increase much beyond the level already present in normal conjuctiva and further influx of mononuclear inflammatory cells is the impetus for growth of the papillae. It is proposed that giant papillary conjunctivitis is a generalized response of the upper tarsal conjunctiva.

Adolescent↗
PubMed1980

Tear histamine levels in vernal conjunctivitis and other ocular inflammations.

Histamine levels were measured in tears from normal volunteers (geometric mean, 5 ng/ml), patients with vernal conjunctivitis (16 ng/ml), and patients with a wide variety of external ocular inflammatory disease (3 ng/ml). Histamine levels were significantly higher in patients with vernal conjunctivitis than in normal subjects (P < 0.01) or patients with other types of ocular inflammation (P < 0.001). We postulate that histamine is an important mediator in the expression of the inflammatory response in vernal conjunctivitis, and that its elevation may be caused by abnormalities in the number of mast cells, the stability of the mast cells or in the system that regulates histamine.

Conjunctivitis↗
PubMed1992

Role of Staphylococcus aureus in chronic allergic conjunctivitis.

A study was undertaken to test the hypothesis that Staphylococcus aureus colonization of the lid margins could determine the expression of allergic eye disease in atopic patients. The authors compared lid isolates of S. aureus from 23 adults who had both atopic dermatitis and chronic conjunctivitis and isolates from 14 patients who had atopic dermatitis but who lacked ocular disease. No significant difference was found in either the staphylococcal protein A or hemolytic toxin production by isolates from the two disease groups, and there was no difference between groups in the quantity of serum IgG nor IgE antibodies to staphylococcal ribitol-teichoic acid. In seven patients with chronic allergic conjunctivitis who were challenged with staphylococcal protein A or heat-killed S. aureus, delayed-type hypersensitivity was not enhanced. These results suggest that although S. aureus colonization of the lids is common in atopic patients, neither the pattern of toxin production nor humoral or cell-mediated immunity to S. aureus play a role in the expression of chronic allergic conjunctivitis.

Adolescent↗
PubMed1992

Paraneoplastic pemphigus, cicatricial conjunctivitis, and acanthosis nigricans with pachydermatoglyphy in a patient with bronchogenic squamous cell carcinoma.

A 77-year-old man with chronic conjunctivitis, acanthosis nigricans with pachydermatoglyphy, and pemphigus-like mucocutaneous lesions was found to have a well-differentiated bronchogenic squamous cell carcinoma. Histopathologic and immunofluorescence studies confirmed the diagnosis of paraneoplastic pemphigus. Skin lesions resolved with oral prednisone and azathioprine therapy, but the conjunctivitis and mucous membrane erosions persisted. The conjunctiva later became scarred with foreshortening of the fornices and development of symblepharon. External beam irradiation arrested the growth of the tumor but did not have any effect on the diseased conjunctiva and other mucous membranes. This case demonstrates that cicatrizing conjunctivitis with bullous mucocutaneous lesions may be a clinical sign associated with an occult neoplasm.

Acanthosis Nigricans↗
PubMed1995

Dry eye with only decreased tear break-up time is sometimes associated with allergic conjunctivitis.

PURPOSE: The authors' clinical experience has suggested that there is a form of dry eye with only decreased tear break-up time, which is associated with allergic conjunctivitis. The current study was performed to verify this hypothesis. METHOD: The authors recruited patients with two types of dry eye syndrome, those with only decreased tear break-up (BUT type) and those with positive vital staining (staining type). Individuals without any symptoms or signs served as controls. All subjects were compared regarding symptoms, Schirmer and tear clearance test results, conjunctival papillary formation, antigen-specific serum-IgE level (s-IgE), and goblet cell density of the palpebral conjunctiva. Antigen-induced allergic conjunctivitis was produced in guinea pigs, and histopathologic changes of the conjunctiva were examined. RESULTS: Patients with the BUT-type dry eye syndrome were younger and their symptoms were as severe as the staining type. The Schirmer and tear clearance test results were better, and the papillary formation and s-IgE were observed more than in the BUT type. The average goblet cell density in the BUT-type syndrome was 625.4 +/- 193.2/mm2, which was significantly less than 1005.6 +/- 294.5/mm2 in the controls (P < 0.01). The average goblet cell density was significantly decreased in the allergic animals (10.40 +/- 1.11/0.2 mm) compared with that of the controls (16.21 +/- 0.26/0.2 mm) or the anti-allergic drug-treated group (13.69 +/- 0.30/0.2 mm) (P < 0.01). CONCLUSION: These results support the authors' hypothesis that decreased break-up time is in part associated with the decreased goblet cell density caused by allergic conjunctivitis.

Adult↗
PubMed1999

A randomized, double-masked, placebo-controlled parallel study of loteprednol etabonate 0.2% in patients with seasonal allergic conjunctivitis.

OBJECTIVE: To evaluate the effects of loteprednol etabonate (LE) 0.2% in reducing the signs and symptoms of seasonal allergic conjunctivitis. DESIGN: Randomized, double-masked, placebo-controlled, parallel group multicenter study of 6 weeks duration. PARTICIPANTS: A total of 135 patients with signs and symptoms of seasonal allergic conjunctivitis participated. INTERVENTION: All patients received either LE 0.2% or placebo (vehicle) four times a day in both eyes for 42 days. MAIN OUTCOME MEASURES: Bulbar conjunctival injection (primary sign) and itching (primary symptom) over the first 2 weeks of treatment was measured. RESULTS: A reduction in severity was seen in both LE and placebo groups for bulbar conjunctival injection (1.5 vs. 1.0 units on a 0-3 scale) and itching (3.4 vs. 3.0 units on a 0-4 scale) over the first 2 weeks. The treatment effect by these measures was -0.5 and -0.4 units in favor of LE (P < or = 0.008). Resolution (i.e., the proportion of patients with signs or symptoms no longer present) at day 14 strongly favored LE-treated patients (36% and 15%; 58% and 38%, for injection and itching, respectively). Both treatments were well tolerated. One patient in each treatment group (1 of 67 and 1 of 68, respectively) had an elevation of intraocular pressure of 10 mmHg or greater during the 6 weeks of treatment. CONCLUSIONS: Loteprednol etabonate 0.2% was more effective than placebo in the treatment of seasonal allergic conjunctivitis. Loteprednol etabonate 0.2% had a safety profile comparable to placebo.

Adult↗
PubMed1999

Conjunctival lymphoma masquerading as chronic conjunctivitis.

OBJECTIVE: Malignant lesions of the conjunctiva may present with slowly evolving signs resembling inflammation. The authors describe the clinical and histopathologic findings of two patients with bilateral conjunctival lymphoma who presented with a history of chronic conjunctivitis without clinically noticeable subconjunctival nodules. DESIGN: Case report. PARTICIPANTS: Two patients. INTERVENTION: Both patients underwent conjunctival biopsy for evaluation of persistent conjunctival inflammation that did not respond to various medical treatment methods. RESULTS: Histopathologic examination revealed extranodal marginal zone B-cell lymphoma (mucosa-associated lymphoid tissue type) in one patient and follicle center lymphoma in the other patient. Both patients subsequently received radiation therapy and achieved a complete remission with no evidence of recurrence in the follow-up period of 20 and 16 months, respectively. CONCLUSIONS: Conjunctival lymphoma should be included in the differential diagnoses of chronic conjunctivitis. Persisting signs and symptoms of conjunctivitis not responding to standard treatment should prompt biopsy.

Adult↗
PubMed2003

Otolaryngological manifestations of ligneous conjunctivitis.

Ligneous conjunctivitis is a rare condition that can involve the mucous membranes of the upper and lower airways and temporal bone extensively. This can lead to life threatening airway obstruction. Involvement of the middle ear and mastoid may cause significant conductive hearing loss. This is the first reported case with temporal bone sections of ligneous conjunctivitis, and awareness of the associated obstructive hydrocephalus may prevent death in this condition. Evidence suggests that plasminogen deficiency may be a causative factor in ligneous conjunctivitis, and this finding may offer new prospects for management.

Autopsy↗