A large case-control study indicates a breed-specific predisposition to feline tooth resorption.

Tooth resorption (TR) is one of the most common dental diseases of cats. It is a painful condition leading to tooth loss. The etiology of TR remains unclear, but old age, breed, other oral and dental diseases, and environmental factors are suspected predisposing factors. In our study, we used part of the data from the extensive feline health online survey of 8115 Finnish cats. As TR is difficult to detect and as the feline health survey included diagnoses defined by both veterinarians and the owners, we limited our study to a subpopulation of cats diagnosed with oral or dental disease by a veterinarian and had dental examination or surgery under sedation (n=944). We utilized case-control study analysed by multivariable logistic regression to determine the risk factors and breed variation of feline TR. The 202 cats diagnosed with TR were defined as TR cases and the remaining 742 cats as controls. The frequency of veterinarian-diagnosed TR was 3.9% in the health survey data (316/8115) and 21% in the subpopulation (202/944). The risk of TR increased with age (14.7% in youngest and 25.3% in oldest age group). Our finding that TR was significantly associated with gingivitis or periodontitis in cats that had also calculus (OR: 2.49 and 3.70, respectively) suggests that inflammatory changes caused by calculus increase the risk of TR. We found that Cornish Rex, European, and Ragdoll are at higher risk for TR (OR: 2.44, 2.98 and 2.90, respectively). Exotic-Persians breed group had lower risk (OR: 0.28). TR was not observed in Turkish van or Devon Rex. The differences between breeds highlight a genetic contribution. In addition, female cats that had food available constantly had significantly less TR than female cats that had feeding times (OR: 0.44). The underlying reasons for this remain unexplained in our study.

Skin atrophy of the eyelid induced by topical ophthalmic corticosteroids.

A case of eyelid skin atrophy caused by long-term application of topical ophthalmic corticosteroids for chronic uveitis is reported. Skin punch biopsy of the uveitic eye showed moderate atrophy of both epidermis and dermis (compared to normal skin on the other eye) resulting from a reduction in the three main fibrous components of the skin, namely type I and type III collagens, and elastic fibers. To our knowledge, this is the first report of skin atrophy in this association.

beta-Amyloid protein immunoreactivity in skin is not a reliable marker of Alzheimer's disease. An autopsy-controlled study.

OBJECTIVES: As a possible diagnostic marker for Alzheimer's disease (AD), we investigated beta-amyloid protein (beta/A4) immunoreactivity in skin. Furthermore, we studied the presence of beta-amyloid precursor protein 695 immunoreactivity in skin. DESIGN: Lifetime skin biopsy specimens were stained for beta/A4 and beta-amyloid precursor protein 695. The follow-up period was 12 months. We determined the correlation between beta/A4 immunoreactivity in skin and brain in patients with a neuropathologic diagnosis. SETTING: All patients with dementia were hospitalized; most of them had moderate to severe dementia. Aged nondemented controls were residents of a nursing home. The Down's syndrome (DS) group included both hospitalized and ambulatory patients. Young nondemented controls were medical students or staff members who volunteered for the study. PATIENTS AND OTHER PARTICIPANTS: The study included a total of 111 subjects. Thirty-five patients had probable AD, nine had possible AD, 15 had multi-infarct dementia, one had idiopathic Parkinson's disease, and one had Parkinson's disease and possible AD. There were also 19 elderly nondemented controls, 23 patients with DS, and eight young nondemented controls. MAIN OUTCOME MEASURES: Immunohistochemical detection of beta/A4 in skin and correlation to the diagnosis of AD. RESULTS: Immunopositivity for beta/A4 antibody was present in and around the endothelium of dermal blood vessels in a proportion of patients with AD and multi-infarct dementia as well as elderly controls. The patients with sporadic AD displayed beta/A4 immunoreactivity significantly more frequently than did patients with familial AD, patients with multi-infarct dementia, and controls. The beta/A4 immunopositivity in skin was rare in the patients with DS and not present in young controls. Instead, 48% of patients with DS but none of other groups had beta-amyloid precursor protein 695 immunoreactivity in skin. Only four (31%) of 13 patients with neuropathologically confirmed AD had shown endothelial beta/A4 immunopositivity in skin biopsy specimens while alive. CONCLUSION: Our results do not support beta/A4 as a diagnostic marker for AD.

Essential cryofibrinogenaemia, leukocytoclastic vasculitis and chronic purpura.

Cryofibrinogenaemia refers to the presence of cold-precipitable proteins in plasma but not in serum. It is usually associated with malignancy, thromboembolic diseases or various inflammatory processes; rarely it may be essential. The most common clinical presentations of cryofibrinogenaemia are cold-intolerance, purpura, skin necrosis and ulcers. We describe a middle-aged woman with essential cryofibrinogenaemia, leukocytoclastic vasculitis, and chronic purpura for over 25 years with several exacerbations. In patients with otherwise unexplained purpura or skin necrosis, determination of plasma cryofibrinogen should be considered.

Screening of effects of selenomethionine-enriched yeast supplementation on various immunological and chemical parameters of skin and blood in psoriatic patients.

Selenium (Se) is known to affect the immune system, and decreased Se-levels in blood of patients with moderate or severe psoriasis have been reported. In this study, the effect of Se-supplementation (400 micrograms/day for 6 weeks as Se-yeast, containing about 70% selenomethionine, SeMet) on skin and blood Se-content, on skin glutathione peroxidase activity and on various chemical and immunological parameters of blood and skin was investigated in 7 psoriatic patients. Before the SeMet-supplementation, serum and blood Se-levels were at the normal range, but they increased 42-45% during the Se-dosage, while zinc levels remained unchanged. Se-dependent glutathione peroxidase activity in both normal and lesional psoriatic skin remained unchanged during the trial, although a small net Se-uptake was detected. At the same time, a slight but statistically significant increase in the number of CD4+ T-cells was observed in the reticular dermis of the psoriatic lesions whereas the numbers of CD8+, CD11c+, and CD1+ cells were not significantly altered. Also, a relatively high number of patients (3 out of 7) showed a strongly reduced number of gamma/delta T-lymphocytes or increased CD8+ T-cells (2 patients) in peripheral blood. However, SeMet-supplementation was not related to these abnormalities or to the number of other peripheral blood immunocytes or to serum immunoglobulin levels. In addition, no marked effect on the clinical condition of the patients was observed. This pilot study suggests that SeMet may be able to modulate the immunological mechanism of psoriatic lesions by increasing the number of CD4+ T-cells.

Association of cutaneous mast cells and sensory nerves with psychic stress in psoriasis.

Association of stress with psoriatic skin symptoms was studied in 13 patients with psoriasis by dividing the patients into low- and high-stress groups based on their clinical examination and answers to three questionnaires (General Health Questionnaire, a somatization scale, and a life change questionnaire). This study focused on skin mast cells and sensory nerves which are the principal components in neurogenic inflammation. Mast cells were stained enzyme-histochemically for tryptase and chymase, and neuropeptides substance P (SP), vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP) were demonstrated immunohistochemically. Compared to the low-stress group (n = 7), the patients in the high-stress group (n = 6) had more severe skin and joint symptoms. Furthermore, mast cells positive for chymase activity were prominently reduced, but tryptase-positive mast cells only slightly decreased in the lesional skin of the high-stress group. A similar tendency was also observed in the nonlesional skin. In the papillary dermis of the lesional skin, both VIP- and CGRP-immunoreactive nerves could be observed in the high-stress group whereas in the low-stress group these nerve fibers were hardly visible in the corresponding area. No association of SP with stress was observed. This study suggests that psychic stress is associated with exacerbation of psoriasis, and stress may induce alterations in the psoriatic lesions by increasing the neuropeptide content with a concomitant decrease in the activity of neuropeptide-degrading enzymes, especially mast cell chymase.

Quantitation of tryptase- and chymase-containing mast cells in cutaneous lichen planus.

The distribution and density of tryptase- and chymase-positive mast cells in lesional and non-lesional cutaneous lichen planus (LP) was analysed. For this, enzyme-histochemical staining techniques and morphometrical measurements were applied. In non-lesional LP skin, chymase-positive cells (TC mast cells) showed a distribution similar to that found in both non-lesional psoriatic skin and in normal skin. Tryptase-positive cells (reflecting both T and TC mast cells), however, were increased in number in the upper dermis of non-lesional LP skin. In lesional LP skin, there were fewer chymase-positive cells in the upper dermis, whereas there were more tryptase-positive cells. In the upper dermis, no differences in the number of tryptase containing cells were detected between lesional and nonlesional LP skin. In lesions of LP and psoriasis, tryptase-positive mast cells are increased but differ in their distribution in the papillary dermis. In psoriatic lesions, tryptase-positive cells are frequently observed in epidermal contact, a feature very rarely seen in LP lesions. The present results suggest that the increased numbers of T mast cells in the upper dermis of nonlesional LP skin may be involved in initiating the LP lesion. It seems unlikely that mast cells could be responsible for the epidermal basal cell damage, though T mast cells do participate in the general inflammatory reaction.

Quantitative enzyme-histochemical analysis of tryptase- and chymase-containing mast cells in psoriatic skin.

Tryptase-containing mast cells have recently been found to be increased in the upper dermis of psoriatic lesions. In the present study, the distribution of chymase- and tryptase-containing mast cells was morphometrically analysed at different dermal levels of lesional and non-lesional psoriatic skin (12 patients) as well as normal human skin. Mast cell tryptase was identified enzyme-histochemically, using Z-Gly-Pro-Arg-MNA as the substrate. For demonstrating mast cell chymase, a simple and specific enzyme-histochemical staining method was developed, using Suc-Val-Pro-Phe-MNA as the substrate. All mast cells positive for chymase were also positive for tryptase and Giemsa stain. Although the number of tryptase-positive mast cells was slightly increased throughout the dermis of lesional psoriatic skin, this increase was most pronounced in the upper dermis immediately beneath, and in close contact with, the epidermis. In contrast, the number of chymase-positive mast cells was clearly decreased in the upper dermis of psoriatic lesions, but not in the deeper dermis, as compared with non-lesional psoriatic skin. In addition, all chymase-positive mast cells observed in the upper dermis were very weakly stained when compared with those in the deeper dermis. No differences were found between non-lesional psoriatic skin and normal skin in which the number of mast cells containing chymase was 72-73% of the number containing tryptase. The present results suggest that T mast cells particularly, containing tryptase but no chymase, proliferate in psoriatic lesions, and that the increase in tryptase activity and the decrease in chymase activity in the upper dermis may lead to an imbalance in the biochemical regulatory systems.

Effect of handling of plasma samples on histamine radio-enzyme assay.

1. Freeze-thawing of plasma samples increased the histamine level at physiological histamine concentrations as analyzed by radio-enzyme assay, but not by high performance liquid chromatography. 2. Heating of plasma samples decreased the histamine levels. 3. Enzymatic or non-enzymatic formation of histamine during handling of plasma samples was not detected. 4. Some albumin preparations contain histamine.

Biochemical and histochemical evaluation of tryptase in various human tissues.

The distribution of tryptase in various human tissue high-salt extracts (skin, lung, pancreas, liver, kidney, and spleen) was studied. Tryptase activity was compared with tissue histamine concentration, chymase activity, and cathepsin D, and histamine-N-methyltransferase (HMT) activities. Tryptase activity, found biochemically in tissue extracts, was localized in tissue sections by an enzyme-histochemical method using peptide 4-methoxy-2-naphthylamide substrates and Fast Garnet GBC as the chromogen. The highest levels of tryptase activity were found in lung and skin extracts. Liver, kidney, and spleen extracts displayed only a little activity. The distribution of histamine was similar to that of tryptase, whereas distributions of cathepsin D and HMT were quite different from that of tryptase. High-salt extracts of lung contained no detectable chymase activity, but in skin extracts this activity was high. Using an enzyme-histochemical method, the tryptase activity in tissue sections seemed solely to be confined to cells, which were granular and Giemsa positive after the red azo dye had been removed with Tween 20. Skin and lung sections contained the highest number of positively stained cells. The inhibition properties of tryptase, found in both tissue extracts and sections, and the substrate profile in tissue sections were identical. Human leukocyte preparation was negative for tryptase when stained enzyme-histochemically. The present results suggest that tryptase in human tissues is found only in the mast cells. The enzyme seems to be identical in the various human tissues studied because the different high-salt extracts were immunologically cross-reactive when tested with a rabbit polyclonal antibody against skin tryptase.

Alpha-fluoromethylhistidine in the treatment of idiopathic cold urticaria.

Alpha-fluoromethylhistidine (alpha-FMH), a new irreversible inhibitor of mammalian histidine decarboxylase, was tested in the treatment of idiopathic cold urticaria in 11 patients. In the initial trial with 50 mg b.i.d., a significant decrease (about 30%) in the total blood histamine level was found after 3 weeks of treatment but clinically there was no improvement in the symptoms of ten cold urticaria patients nor in the responses to the ice-cube test. In the second trial with three patients suffering from severe idiopathic cold urticaria, a higher dose of up to 500 mg b.i.d. of alpha-FMH for 3 weeks resulted in a marked decrease in the total blood histamine level as well as in an apparent inhibition of histamine synthesis in the skin previously exposed several times to cold water. The symptoms of cold urticaria and the responses in the ice-cube tests also decreased simultaneously. No clinical side effects nor changes in laboratory analysis were seen during the treatment with alpha-FMH. These results suggest that alpha-FMH may be useful in the treatment of severe cold urticaria especially in combination with histamine exhaustion of mast cells using cold water.

The BB-isoenzyme is a major component of creatine kinase in skin blister fluid.

We measured levels of creatine kinase and its three isoenzymes in serum and blister fluid from 16 healthy volunteers. The BB-isoenzyme was found to be the predominant form in blister fluid while only the MM isoenzyme was found in serum. The levels of BB-isoenzyme in blister fluid decreased as the blisters aged. The source of BB-isoenzyme in blister fluid is most probably the damaged epidermis.

Comparison of the new antihistamine acrivastine (BW 825C) versus cyproheptadine in the treatment of idiopathic cold urticaria.

A double-blind, crossover trial with a new triprolidine derivative, acrivastine (BW 825C; 8 mg 3 times daily), cyproheptadine (4 mg 3 times daily) and placebo was carried out in 18 patients suffering from idiopathic cold urticaria. Acrivastine and cyproheptadine significantly (p less than 0.01) reduced weal areas following ice cube challenge when compared to placebo. Acrivastine was found to be significantly more effective (p less than 0.01) than cyproheptadine in reducing weal areas. Furthermore, cyproheptadine caused significantly more drowsiness than acrivastine (p = 0.021) or placebo (p = 0.013), which did not differ from each other. This study shows that acrivastine is an effective agent in the treatment of cold urticaria and suggests that acrivastine in the dose used lacks adverse effects, such as drowsiness, traditionally associated with antihistamine therapy.

Cold urticaria. Clinical findings in 220 patients.

Patients with cold urticaria, a total of 220, were studied in Finland. Sixty-three percent of the patients were female. The diagnosis was based on a positive ice cube test in 90% of cases, and the other cold tests were needed to certify the diagnosis for the remainder of patients. The mean age at the onset of the disease was 25.1 years (range, 1-74), and the mean duration of symptoms was 6.3 years (range, 3 weeks to 37 years). Cold urticaria symptoms had disappeared in fifty-three patients (24%), but there was a recurrence of the disease in twelve. Idiopathic (primary acquired) cold urticaria was present in 96% of the patients. Only two patients had a secondary acquired cold urticaria. Two patients had cold-induced, "cholinergic" urticaria, and four patients had a delayed type of cold urticaria. Twenty-one percent of the patients had dermatographism, 8% had cholinergic urticaria, and two patients (1%) had heat urticaria concurrently with cold urticaria.

Comparison of the short-duration dithranol and Dithrocream therapy in the treatment of psoriasis.

Short-duration dithranol therapy (SDDT) was compared to Dithrocream therapy in an open trial for the treatment of psoriasis. SDDT is based on the application of highly concentrated (1-2%) dithranol (anthralin) for a short period of time (10-20 min) and appeared to be clearly less staining and more comfortable than Dithrocream (0.1-0.5%). Both treatment methods appeared to be clinically effective; the SDDT method was slightly more effective than Dithrocream in this study.