Urtica dioica pollen allergy: Clinical, biological, and allergomics analysis.

BACKGROUND: The most emblematic members of Urticaceae at allergic risk level are wall pellitories (Parietaria), whereas nettle (Urtica) pollen is considered as poorly allergenic. No allergen from nettle pollen has yet been characterized, whereas 4 are listed for Parietaria pollen by the International Union of Immunological Societies. Clinical and biological profiles of 2 adult men who developed symptoms against nettle pollen and/or leaves were studied. OBJECTIVE: To characterize the allergic reaction and identify the potential nettle pollen sensitizing allergens. METHODS: IgE-mediated reaction to nettle pollen extract was evaluated by skin prick test, immunoassay, nasal provocation, and basophil activation test. To characterize specific nettle pollen allergens, an allergomic (IgE immunoproteomic) analysis was performed combining 1- and 2-dimensional electrophoresis, IgE immunoblots of nettle pollen extract, identification of allergens by mass spectrometry, and database queries. RESULTS: The results of biological and immunochemical analyses revealed that the allergic rhinitis was due to Urtica dioica pollen in both patients. The allergomic analysis of nettle pollen extract allowed the characterization of 4 basic protein allergens: a thaumatin-like protein (osmotin) with a relative molecular mass of 27 to 29 kDa, a pectinesterase (relative molecular mass, 40 kDa), and 2 other basic proteins with relative molecular masses of 14 to 16 kDa and 43 kDa. There is no or only very weak allergen associations between pellitory and nettle pollen. CONCLUSION: Exposure to nettle pollen can be responsible of allergic symptoms, and several allergens were characterized. Unravelling the allergens of this underestimated allergy might help to improve diagnosis and care for patients, to predict cross-reactivities and design adapted specific immunotherapy.

Beyond hemostasis: the challenge of treating plasminogen deficiency. A report of three cases.

Congenital plasminogen deficiency is a rare autosomal recessive disorder, characterized by chronic mucosal membranous lesions. Although the most common clinical manifestation is eye involvement as ligneous conjunctivitis, extra-ocular lesions affecting other mucosal surfaces indicates a systemic disease. In this report we describe two cases with atypical extra-ocular involvement that includes pericarditis and recurrent hematocolpos, and one with paradoxical correlation between ocular lesions and plasminogen levels. In ligneous conjunctivitis, although different treatment strategies have been tried with mild success, the only effective therapy is topical or systemic plasminogen concentrates that are not commercially available. Unfortunately there is not either effective management for cases with multisystemic disease. Hence, treatment for plasminogen deficiency is still a challenge and the variability of the clinical spectrum in this pathology makes necessary a multidisciplinary approach.

Seasonal Local Allergic Rhinitis in Areas With High Concentrations of Grass Pollen.

BACKGROUND: Local allergic rhinitis (LAR) is a phenotype of allergic rhinitis characterized by the presence of a localized immune response in the nasal mucosa of patients with negative skin prick test (SPT) results and undetectable serum specific IgE (sIgE). It unknown whether LAR is limited to areas with low or moderate aeroallergen exposure. OBJECTIVE: To explore the presence of LAR and the clinical and immunological characteristics of this entity in geographic areas with high grass pollen loads. METHODS: A cross-sectional observational study was carried out in 2 hospitals in central Spain (Madrid and Ciudad Real). Sixty-one patients with seasonal rhinitis and negative SPT results and undetectable serum sIgE were evaluated using a clinical questionnaire, determination of serum total IgE, and a nasal allergen provocation test (NAPT) with Phleum species. The response to NAPT was monitored using assessment of nasal symptoms, acoustic rhinometry, and determination of sIgE, tryptase, and eosinophil cationic protein in the nasal cavity. RESULTS: Seasonal LAR was detected in 37 patients (61%) using the techniques described above. Eleven percent of patients with LAR were adolescents or children, and 14% reported onset of rhinitis in childhood. Most patients reported persistent-moderate seasonal nasal symptoms, and 41% reported worsening of the disease during the last 2 years. Conjunctivitis was the most common comorbidity, affecting 95% of cases. CONCLUSIONS: LAR to grass pollen is relevant in patients with seasonal symptoms indicative of allergic rhinitis but with a negative skin test result who live in areas with high allergenic pollen loads. This entity should be included the differential diagnosis of rhinitis.

[Evaluation of some immunological indexes in children with allergic diseases and obesity].

AIM: Study some immunological indexes in children with allergic diseases depending on bodyweight and clinical manifestations of allergy. MATERIALS AND METHODS: A correlation analysis of relationship of indexes of natural resistance (phagocytosis, complement), immunoglobulin level and main lymphocyte populations with body weight in 214 children aged 12 - 17 years with various allergic diseases (rhinitis/ rhinoconjunctivitis, atopic dermatitis, bronchial asthma) was carried out. The children were divided into groups based on body mass index (BMI): 73 (34%) children with normal weight, 74 (35%) overweight and 67 (31%) obese. RESULTS: The analysis has shown that the frequency of detection of children with obesity is the highest for age 12 - 14 years. With the increase of age the number of obese children decreases (OR - 9.0; 95% CI: 1.56 - 51.87; p = 0.008 and OR - 0.27; 95% CI: 0.08 - 0.94; p = 0.04, respectively). An interrelation of BMI with clinical exacerbations of allergy was detected. Out of 166 patients with allergic diseases combined with bronchial asthma excessive weight was detected in 62 (37%), obesit--in 57 (34%) and normal weigh--in 47 (28%). In a group of 48 children with allergy without asthma excessive weight was noted in 12 (25%), obesit--in 10 (21%) and normal weigh--in 26 (54%) of patients. In children with bronchial asthma excessive weight occurs almost 3 times more frequently than in children with allergy and without asthma. Differences could not be detected in 3 groups of children when immune status indexes were compared, except total IgE and NK cell levels. Total IgE level was the highest in obese children (2.7 log), differed significantly from the level in obese (2.46 log) and normal weight (2.37 log, r = 0.32, p < 0.05) children. The relative content of NK cells in blood of obese children was significantly higher than in children withnoormal and excessive weight (r = 0.41). The analysis of significant correlation coefficient indexes detected correlative associations of some immunological indexes with BMI. In overweight children a negative relation between the level of complement and BMI (r = -0.61) and positive relation with phagocytosis index (r = 0.58) were detected. CONCLUSION: Obesity in children with allergic diseases is associated with an increase of conjugation of immunological indexes manifesting in an increase of number of natural killers (NK), phagocytosis indexes, increased total IgE level against the background of negative interrelation with the main populations of lymphocytes, that in general influences aggravation of allergopathology in the form of a higher frequency of detection of atopic bronchial asthma.

Ketocarotenoid circulation, but not retinal carotenoid accumulation, is linked to eye disease status in a wild songbird.

Pathogenic or parasitic infections pose numerous physiological challenges to organisms. Carotenoid pigments have often been used as biomarkers of disease state and impact because they integrate multiple aspects of an individual's condition and nutritional and health state. Some diseases are known to influence carotenoid uptake from food (e.g. coccidiosis) and carotenoid use (e.g. as antioxidants/immunostimulants in the body, or for sexually attractive coloration), but there is relatively little information in animals about how different types of carotenoids from different tissue sources may be affected by disease. Here we tracked carotenoid accumulation in two body pools (retina and plasma) as a function of disease state in free-ranging house finches (Haemorhous mexicanus). House finches in eastern North America can contract mycoplasmal conjunctivitis (Mycoplasma gallisepticum, or MG), which can progress from eye swelling to eye closure and death. Previous work showed that systemic immune challenges in house finches lower carotenoid levels in retina, where they act as photoprotectors and visual filters. We assessed carotenoid levels during the molt period, a time of year when finches uniquely metabolize ketocarotenoids (e.g. 3-hydroxy-echinenone) for acquisition of sexually selected red plumage coloration, and found that males infected with MG circulated significantly lower levels of 3-hydroxy-echinenone, but no other plasma carotenoid types, than birds exhibiting no MG symptoms. This result uncovers a key biochemical mechanism for the documented detrimental effect of MG on plumage redness in H. mexicanus. In contrast, we failed to find a relationship between MG infection status and retinal carotenoid concentrations. Thus, we reveal differential effects of an infectious eye disease on carotenoid types and tissue pools in a wild songbird. At least compared to retinal sources (which appear somewhat more temporally stable than other body carotenoid pools, even to diseases of the eye evidently), our results point to either a high physiological cost of ketocarotenoid synthesis (as is argued in models of sexually selected carotenoid coloration) or high benefit of using this ketocarotenoid to combat infection.

Soluble trail as a marker of efficacy of allergen-specific immunotherapy in patients with allergic rhinoconjunctivitis.

BACKGROUND: Allergic rhinitis is a common health problem affecting the immune system. The homeostasis of the immune system is regulated by apoptosis. In this study, serum circulating soluble TRAIL levels of allergic rhinoconjunctivitis patients before and after allergen-specific immunotherapy were evaluated. MATERIAL/METHODS: The sTRAIL levels of pre- and post-treated allergic rhinoconjunctivitis patients (n=25) were compared to age- and sex-matched healthy individuals (n=25). sTRAIL levels were measured by ELISA. The skin prick test (SPT) results were recorded before and after treatment. RESULTS: The sTRAIL levels between the pre-treated and control groups were significantly different (p<0.0001). However, there was no significant difference between the post-treated group and healthy individuals (p=0,801). SPT was a statistically significant difference between the values of the research group before and after immunotherapy (grasses mixture, barley mixture, Oleaauropeae, D. Pteronyssinus, D. farinae). CONCLUSIONS: The sTRAIL levels were decreased after allergen-specific immunotherapy to healthy levels and may be of use as a marker of efficacy of immunotherapy in allergic rhinoconjunctivitis patients.

Induction of bilateral ligneous conjunctivitis with the use of a prosthetic eye.

The purpose of this article to report a case of ligneous conjunctivitis in an anophthalmic socket, in respect of a 20-year-old woman. The subject woman had a history of left enucleation surgery presented with bilateral palpebral ligneous conjunctivitis and ligneous gingivitis. The hematologic study revealed a severe plasma plasminogen deficiency. The eyelid lesions were successfully treated with surgical excision, topical heparin and corticosteroid eyedrops. However, the ligneous lesions recurred bilaterally after she was fitted with a prosthetic eye and were refractory to intensive topical treatment with heparin and cyclosporin A eye drops. This case shows that the use of a prosthetic eye may induce ligneous conjunctivitis in an anophthalmic socket and normal eye which is refractory to topical treatment.

IgE Ratio in Tears: A Predictive Tool of Ocular Allergic Inflammation.

PURPOSE: To demonstrate the tear IgE (measured/exuded) ratio (R) as a useful biological marker of ocular allergy in order to distinguish severe from less severe inflammatory status. METHODS: Tear samples and sera from 78 ocular allergy patients and 19 control subjects were analyzed. Total IgE and albumin were measured for calculating the tear IgE-R defining two subgroups (SG) of samples: R ≥ 4-SG and R < 4-SG. Eosinophil cationic protein, Th1 and Th2 cytokines (IFN-γ, IL-4, -5, -6, -8 and -10) and protein electrophoretic profiles were also investigated in tears. RESULTS: The R < 4-SG compared to the R ≥ 4-SG shows higher levels of tear albumin, eosinophil cationic protein, and Th1 and Th2 cytokines. Moreover, each subgroup presents a specific protein profile. CONCLUSION: This study showed that an IgE-R lower than four must be carefully interpreted as a warning sign of a severe inflammatory context and should be also associated with an exploration of immunological profile.

Associations of adipokines with asthma, rhinoconjunctivitis, and eczema in German schoolchildren.

There is growing evidence for an association between obesity and asthma, but little is known about the underlying mechanisms. We hypothesized that high plasma leptin and low plasma adiponectin concentrations might be related to asthma and allergies in children. Plasma leptin and adiponectin concentrations were measured in a cross-sectional study involving 462 children aged 10 years. Information on disease symptoms and diagnosis was collected by parental questioning. Multivariate linear and logistic regression models were used to assess the association between biomarkers and disease. High leptin levels were associated with increased lifetime prevalence of asthma [odds ratio (OR): 3.76; 95% confidence interval (CI): 1.42-9.92]. The relationship was particularly strong for non-atopic asthma (OR: 5.51; 95% CI: 1.99-17.51). No associations were observed between plasma leptin levels and hay fever, and rhinoconjunctivitis. Low adiponectin levels were associated with increased prevalence of both symptoms of atopic dermatitis (OR: 3.23; 95% CI: 1.28-7.76) and ever-diagnosed eczema (OR: 2.35; 95% CI: 1.13-4.89). In girls and non-atopic children, stronger associations for both leptin and adiponectin levels with asthma than in boys and atopic children were observed. These results suggest that adipokines may contribute to increased asthma and allergy risk in obese subjects. Stronger associations among girls with non-atopic asthma may indicate diverse pathological mechanisms.

Ligneous conjunctivitis with oral mucous membrane involvement and decreased plasminogen level.

Ligneous conjunctivitis (MIM 217090) is a rare autosomal recessive hereditary disorder. We report a case with both ligneous conjunctivitis and ligneous periodontitis in association with plasminogen type I deficiency. Diagnosis was based on the clinical and histological findings and most importantly, decreased serum level of plasminogen type I.

Association of combined IL-13/IL-4R signaling pathway gene polymorphism with Stevens-Johnson syndrome accompanied by ocular surface complications.

PURPOSE: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute-onset mucocutaneous diseases induced by infectious agents or inciting drugs. The authors previously reported an association between SJS/TEN and IL-4R gene polymorphism that is essential for IL-4 and IL-13 signaling. To examine IL-4 and IL-13 gene polymorphisms and the combination of these polymorphisms with IL-4R polymorphism, the authors performed polymorphism analysis. METHODS: In 76 Japanese SJS/TEN patients with ocular surface complications and 160 healthy controls, the authors analyzed polymorphisms of the promoter -590C/T in the IL-4 gene and of the promoter -1111C/T and Arg110Gln in the IL-13 gene and assessed Gln551Arg in the IL-4R gene. Because Arg110Gln affects serum IL-13, plasma IL-13 levels were also examined. RESULTS: In the SJS/TEN patients, the Arg110Gln SNP of IL-13 was significantly associated with the disease, and the frequency of Arg110 alleles was significantly higher than that in the controls. Plasma IL-13 tended to be lower in SJS/TEN patients than in the controls. Analysis of the genotype pattern of IL-4R SNP Gln551Arg and IL-13 SNP Arg110Gln showed that the Gln551Gln(A/A)-Arg110Arg(G/G) genotype pattern was also associated with SJS/TEN. CONCLUSIONS: IL-13 gene polymorphisms might be associated with SJS/TEN with ocular surface complications. The present findings suggest that SJS/TEN is different from allergic diseases such as atopy and asthma because the ratio of each allele in the IL-13 SNP Arg110Gln was the opposite of the ratio in those diseases. They also reveal that combined polymorphisms in the IL-13/IL-4R signaling pathway were associated with SJS/TEN with ocular surface complications.

Plasminogen deficiency.

Plasminogen deficiency has emerged as a well-recognized disorder in which reduced levels of plasminogen lead to the development of pseudo membranes on mucosal surfaces, with subsequent end-organ damage of the affected tissue. Ligneous conjunctivitis is the most recognizable, well-documented, and common presentation of the clinical syndromes associated with plasminogen deficiency, although numerous other organs have been reported to be affected. Interestingly, while plasminogen deficiency was initially believed to be related to development of venous thromboembolic disease, more recent data suggest that decreased plasminogen levels may not, in and of themselves, increase the risk of thrombosis. Two types of plasminogen deficiency have been described in the literature. Type I represents a quantitative deficiency and type II a qualitative deficiency. It appears that hypoplasminogenaemia (type I deficiency) is the type most associated with pseudomembrane disease. A variety of genetic mutations has been identified recently and is reported to lead to these disorders. These defects have been identified in diverse populations, with no specific ethnic predilection. However, this disorder may have increased prevalence in areas and communities where consanguinity is more common. Despite the fact that the characteristic lesions are now better recognized and plasminogen levels are accurately and easily measured, adequate treatment of the clinical manifestations of this disorder is lacking. For ligneous conjunctivitis, a plasminogen concentrate formulated into an ophthalmologic preparation has been found to be an effective local therapy. Unfortunately, no plasminogen concentrate is currently available commercially for either systemic or local therapy.

Plasminogen Tochigi mice exhibit phenotypes similar to wild-type mice under experimental thrombotic conditions.

Plasminogen (Plg) is a precursor of plasmin that degrades fibrin. A race-specific A620T mutation in Plg, also known as Plg-Tochigi, originally identified in a patient with recurrent venous thromboembolism, causes dysplasminogenemia with reduced plasmin activity. The Plg-A620T mutation is present in 3-4% of individuals in East Asian populations, and as many as 50,000 Japanese are estimated to be homozygous for the mutant 620T allele. In the present study, to understand the changes of thrombotic phenotypes in individuals with the mutant 620T allele, we generated knock-in mice carrying the homozygous Plg-A622T mutation (PlgT/T), an equivalent to the A620T mutation in human Plg. PlgT/T mice grew normally but showed severely reduced plasmin activity activated by urokinase, equivalent to ~8% of that in wild-type mice. In vitro fibrin clot lysis in plasma was significantly slower in PlgT/T mice than in wild-type mice. However, all experimental models of electrolytic deep vein thrombosis, tissue factor-induced pulmonary embolism, transient focal brain ischaemic stroke, or skin-wound healing showed largely similar phenotypes between PlgT/T mice and wild-type mice. Protein S-K196E mutation (Pros1E/E) is a race-specific genetic risk factor for venous thromboembolism. Coexistence in mice of PlgT/T and Pros1E/E did not affect pulmonary embolism symptoms, compared with those in Pros1E/E mice. Hence, the present study showed that the Plg-A622T mutation, which confers ~8% plasmin activity, does not increase the risk of thrombotic diseases in mice under experimental thrombotic conditions and does not modify the thrombotic phenotype observed in Pros1E/E mice. PlgT/T mice can be used to investigate the potential pathophysiological impact of the Plg-A620T mutation.

Novel plasminogen gene mutations in Turkish patients with type I plasminogen deficiency.

The plasminogen (Plg) protein is the inactive proenzyme form of plasmin that dissolves fibrin thrombi by a process called fibrinolysis. It has been shown that homozygous or compound-heterozygous deficiency of this protein is a major cause of a rare inflammatory disease affecting mainly mucous membranes found in different body sites. In this study, five individual Turkish patients and nine Turkish families with type 1 Plg deficiency were investigated for PLG gene mutations. All of the coding regions of the PLG gene mutations were screened for mutations using denaturing high-pressure liquid chromatography (DHPLC). Samples showing a different DHPLC profile were subjected to DNA sequencing analysis. Here, we described five novel mutations namely, Cys49Ter, +1 IVS6 G>A, Gly218Val, Tyr283Cys, and Gly703Asp. Previously identified five nonsynonymous (Lys38Glu, Glu180Lys, Gly420Asp, Asp453Asn, Pro763Ser), five synonymous (330 C>T, 582 C>T, 771 T>C, 1083 A>G, 2286 T>G), and a 3' untranslated region (3' UTR) mutation (c.*45 A>G) were also reported in this present study. In this study, we have identified a total of eight mutations, five of which are novel. The mutations/polymorphisms identified in eight of the patients do not explain the disease phenotype. These cases probably carry other pathological mutations (homozygous or compound heterozygous) that cannot be detected by DHPLC.

Human homozygous type I plasminogen deficiency and ligneous conjunctivitis.

On the basis of a questionnaire sent to the ophthalmology departments of hospitals throughout Germany, 10 patients with ligneous conjunctivitis or pseudomembranous disease, ranging in age from 1 to 71 years were identified. All 10 patients had severely reduced plasminogen levels. Genetic analysis revealed homozygous type I plasminogen deficiency (which had not previously been described in humans) in 7 patients and compound heterozygous plasminogen deficiency in 1 patient. Clear differentiation was not possible in 2 patients. Most of the parents had heterozygous plasminogen deficiency. None of the patients had experienced any episodes of thrombosis. Additionally, the following observations were made: 1) Levels of polymorphonuclear (PMN)-elastase protein were markedly elevated in 6 of 6 patients and 10 of 11 parents tested, and levels were higher in homozygotes than in heterozygotes. 2) Hereditary factor XII deficiency was found in 3 of 6 patients tested. 3) C1-inhibitor was elevated in 2 of 4 patients, prekallikrein was elevated in 1 of 4 patients, and plasminogen activator inhibitor type 1 was elevated in 1 of 4 patients. Infusions of lys-plasminogen concentrate induced pronounced fibrinolytic activity as indicated by high levels of D-dimer, increases in plasmin-antiplasmin complex and decreases in polymorphonuclear elastase. C1-inhibitor, prekallikrein and PAI-1 normalized after repeated infusions of lys-plasminogen. In contrast to dysplasminogenemia, severe type I plasminogen deficiency might be seen as a problem of extravascular space, in particular of the mucous membranes, possibly triggered by mechanically induced or inflammatory lesions of the vessels supplying the tissue.

Red eyes in renal failure.

Of 57 patients with chronic renal failure who all had deposition of calcium salts in the conjunctival and corneal tissue two developed a brief episode of painful irritation and redness of the conjunctiva and subconjunctiva. This hyperaemia was adjacent to erosions of the corneal epithelium of the eye as a consequence of exfoliation of calcium concretions from the superficial corneal epithelium. Eight patients showed inflammatory reactions of the conjunctivae that were clinically identical to inflamed pingueculae. Three patients showed an inflammatory reaction of the eye that was characterised by a waxy red, more or less diffuse, episcleral and conjunctival hyperaemia extending beyond the palpebral fissure. The average value of the serum calcium concentration in these patients was particularly high and statistically significantly higher than in patients with calcification but without inflammatory signs and also higher than in patients who showed pingueculitis. We propose to reserve the term 'red eye of renal failure' for the latter group of patients.

Ligneous conjunctivitis: biochemical evidence for hypofibrinolysis.

Ligneous conjunctivitis (LC) is a rare disease of unknown etiology characterized by the growth of "woody" plaques on ocular and extraocular mucosa. These lesions are comprised of fibrin and both direct and indirect evidence implicates hypofibrinolysis as the primary defect in LC. To further elucidate the pathophysiology of LC we investigated the biochemical aspects of ligneous lesions with respect to the fibrinolytic system. Ligneous lesions were obtained from the right eye of a 15 year-old female patient with longstanding LC since age 2.5 year. Ligneous conjunctivitis in this patient has exhibited a chronic recurrent coarse and has involved multiple muscosal sites. Samples analyzed included an abundant mucoid thread from the conjunctival fornix and the ligneous plaque attached to the inferior tarsus. Samples were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to characterize protein profiles and by a variety of zymographic methods to visualize fibrinolytic enzymes. We found that mucoid and ligneous samples were distinct entities. Specifically, ligneous samples contained polypeptides with electrophoretic profiles characteristic of intact fibrin, and were replete in fibrin-bound tissue plasminogen activator (t-PA). Despite the presence of ample t-PA, ligneous samples were essentially devoid of fibrinolytic activity. In contrast, neither proteins nor t-PA could be detected in mucoid samples when fractionated by 7.5-15% SDS-PAGE or analyzed by fibrin zymography, respectively. Despite the absence of t-PA, mucoid samples were replete in fibrinolytic activity. This activity was plasminogen independent, heterogenous and inhibited by PMSF. Degradation profiles suggested that this activity represented in part alpha-chymotrypsin, consistent with this patient's treatment regime, as well as plasmin, elastase and an unidentified neutrophil-derived activity. Interestingly, ligneous samples contained both latent and activated forms of matrix metalloproteinase-9 (MMP-9), whereas mucoid samples contained predominantly activated forms of MMP-9. LC is characterized by defective fibrinolysis, despite the presence of ample t-PA and intact fibrin, and by an abundant mucoid thread which binds both endogenous and exogenous enzymes including serine protease(s) and collagenase(s). The implications of these results with respect to a role for exuberant mucus production or abnormal mucins in the development of a relative mucosal-site specific plasmin(ogen) deficiency is discussed.

[Vitamin A and carotene concentration in serum in persons with chronic conjunctivitis and pterygium]. / Vitamin-A-und Carotinkonzentrationen im Serum bei Personen mit chronischer Conjunctivitis und Pterygium

In 41 persons with chronic conjunctivitis, 28 persons with pterygium and 61 eye-healthy persons the Vitamin A and carotene blood level have been examined. All persons with chronic conjunctivitis and pterygium have subjective eye disturbances. In persons with chronic conjunctivitis the vitamin A blood level was lower (men 32 mcg%, women 20 mcg%). In almost all persons with chronic conjunctivitis and pterygium delayed dark adaptation was recorded and the skin-mucosal changes are more frequent.

Hematology of fledgling Manx shearwaters (Puffinus puffinus) with and without 'puffinosis'.

Hematological parameters were measured in 14 fledgling Manx shearwaters (Puffinus puffinus), with the disease puffinosis and in 10 birds that did not have the disease, on the Island of Skomer between 2 and 11 September 1991. The mean plasma fibrinogen concentration was significantly higher in the diseased birds and some of these had abnormally elevated monocyte counts. No other significant differences were observed.