Treatment for crusted scabies: limitations and side effects of treatment with ivermectin.

Skin eruption with mild itching of the hands and feet developed in a man in his 90s 1 month after he was hospitalized following a traffic accident. Scabies was diagnosed in an attending nurse 3 months after the patient's hospitalization, and infection from the patient was suspected. Cornification of the patient's soles and marked hypertrophy of the nails of both feet were observed. After a large number of scabies mites were detected on microscopic examination, crusted scabies was diagnosed. The patient was given oral ivermectin, 6 mg, once per week for 3 weeks, and crotamiton topical ointment containing 30% benzyl benzoate was applied on the body from the neck down. However, because a large number of scabies mites were detected again on microscopic examination, the dose of ivermectin was increased to 12 mg and administered 3 times. One week after the sixth dose of ivermectin was administered, hemorrhagic scabs around the mouth and erosion of the tongue developed. Mucosal drug eruption was suspected, and eruptions around the mouth and on the tongue resolved within 1 week after ivermectin being discontinued. 1% gamma-benzene hexachloride ointment was applied topically on the body from the neck down once a week, crotamiton ointment containing benzyl benzoate was applied daily, and the hypertrophic parts of the nails were removed. The patient subsequently achieved a full recovery.

Neutrophilic inflammation and CXC chemokines in patients with refractory asthma.

BACKGROUND: There is evidence that eosinophils and neutrophils are simultaneously increased in the airways of some patients with chronic refractory asthma. The mechanisms by which neutrophils accumulate in the airways of asthmatics remain to be elucidated, however, chemoattractants for neutrophils such as CXC chemokines may affect either the accumulation or functional status of neutrophils in such patients. The objective of the present study was to identify the CXC chemokine responsible for the neutrophilic and possibly eosinophilic inflammation observed in the airways of patients with refractory asthma. METHODS: Following the inhalation of hypertonic saline, induced sputum was obtained from 14 healthy controls, 16 patients with mild well-controlled nonrefractory asthma, and 14 patients with refractory asthma. Concentrations of CXC chemokines and differential inflammatory cell counts were determined. RESULTS: The percentages of induced sputum eosinophils were significantly higher both in patients with nonrefractory asthma and in patients with refractory asthma. On the other hand, the percentages of neutrophils were increased only in sputum from patients with refractory asthma. The concentration of IL-8, but not ENA-78 or GRO-alpha, was also significantly increased in induced sputum from patients with refractory asthma. The concentration of IL-8 correlated significantly with the percentages of neutrophils. CONCLUSIONS: The results of the present study suggest that IL-8, but not ENA-78 or GRO-alpha, may contribute to the observation of neutrophilic inflammation in patients with refractory asthma.

Usefulness and pharmacokinetic study of oral terbinafine for hyperkeratotic-type tinea pedis.

To study and establish an optimal administration method of oral antifungal, terbinafine (TBF), for hyperkeratotic-type tinea pedis from the pharmacokinetic point of view, 20 patients with hyperkeratotic-type tinea pedis were given TBF 125 mg once daily for 4 weeks and observed over time for improvement of dermatological symptoms and mycological efficacy. Targeting five of the patients, TBF concentration in the stratum corneum was measured using the LC-MS/MS method. TBF was detected in the stratum corneum of the sole 1 week after beginning the treatment in some cases and reached its peak 1 week after the completion of the treatment with a concentration of 247.8 ng g(-1), which was approximately more than 50 times higher than its minimal inhibitory concentration against dermatophytes. TBF was not detected at 8 weeks post-treatment, although its concentration was 50.73 ng g(-1) at 6 weeks post-treatment. All cases were subjected to analysis for final total efficacy, general safety and usefulness. Its effectiveness rate (effective + markedly effective) was 95% (19/20) with no adverse reactions, including abnormal changes in the laboratory test values, in any patients. From the above, it is noted that TBF showed excellent efficacy and safety for refractory hyperkeratotic-type tinea pedis, and also it was considered as a useful drug to treat cutaneous mycosis, including hyperkeratotic-type tinea pedis, from the pharmacokinetic point of view.

Usefulness and pharmacokinetic study of oral terbinafine for hyperkeratotic type tinea pedis.

To study and establish an optimal administration method of oral antifungal, terbinafine (TBF), for hyperkeratotic type tinea pedis, from the pharmacokinetic point of view, 20 patients with hyperkeratotic type tinea pedis were given TBF 125 mg once daily for 4 weeks and observed over time for improvement in dermatological symptoms and mycological efficacy. Targeting five of the patients, TBF concentration in the stratum corneum was measured using the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. TBF was detected in the stratum corneum of the sole 1 week after beginning the treatment in some cases and reached its peak 1 week after the completion of the treatment with a concentration of 247.8 ng g(-1), which was approximately more than 50 times higher than its minimal inhibitory concentration against dermatophytes. TBF was not detected at 8 weeks post-treatment, although its concentration was 50.73 ng g(-1) at 6 weeks post-treatment. Its effectiveness rate (effective + markedly effective) was 95% (19/20) with no adverse reactions, including abnormal changes in the laboratory test values, in any patient. These results suggest that TBF is a useful drug to treat hyperkeratotic tinea pedis from the pharmacokinetic point of view.

Systemic lupus erythematosus-associated cutaneous cryptococcosis treated successfully with an intermittent 3-day on/off cycle of itraconazole.

We describe a case of systemic lupus erythematosus (SLE)-associated cutaneous cryptococcosis. A 32-year-old woman with SLE and lupus nephritis presented with the erythematous maculae on the chest and the extremities, in which encapsulated yeasts were revealed, and was diagnosed with secondary cutaneous cryptococcosis. We administered fluconazole (FLCZ) and then itraconazole (ITCZ) instead of amphotericin B (AMPH-B) to avoid the risk of renal toxicity of AMPH-B in the patient. While treatment with FLCZ was not particularly effective, repeated intermittent administration of ITCZ on a "3-day on/off cycle" (i.e. medication on 3 consecutive days and suspension for the next 3 days in turn) achieved complete remission of the cryptococcosis.

Eosinophils do not enhance the trans-basement-membrane migration of neutrophils.

BACKGROUND: There is increasing evidence that both neutrophilic and eosinophilic inflammation persist in the airways of patients with severe asthma. We have reported a positive relationship between the concentrations of eosinophils and neutrophils in sputum from severe asthmatics, suggesting a possible role of eosinophils in regulating neutrophilic inflammation. The aim of this study was to investigate whether activated eosinophils modify the trans-basement membrane migration (TBM) of neutrophils. METHODS: Eosinophils and neutrophils were isolated from peripheral blood drawn from healthy donors. The TBM of neutrophils in response to a variety of chemoattractants was evaluated in the presence or absence of eosinophils by using the chambers with a Matrigel-coated Transwell insert. RESULTS: As expected, eotaxin (10 nM) and RANTES (10 nM), but not IL-8 (10 nM), induced the TBM of eosinophils. On the contrary, only IL-8 induced the TBM of neutrophils. When eosinophils were coincubated with neutrophils and stimulated with IL-8, the TBM of eosinophils was significantly augmented. On the other hand, when neutrophils were coincubated with eosinophils and stimulated with eotaxin or RANTES, the TBM of neutrophils was not modified. CONCLUSIONS: Neutrophils migrated by IL-8 may lead eosinophils to accumulate in the airways of patients with severe asthma. On the other hand, it is unlikely that eosinophils migrated by chemoattractants such as CC chemokines regulate neutrophilic inflammation.

Theophylline attenuates the neutrophil-dependent augmentation of eosinophil trans-basement membrane migration.

BACKGROUND: Recent evidence suggests that both neutrophilic and eosinophilic inflammation persist in the airways of patients with severe asthma. Neutrophils can secrete a variety of mediators which may augment the migration of eosinophils. We have reported that activated neutrophils augment the trans-basement membrane migration (TBM) of eosinophils in vitro. Theophylline has been shown to modulate some functions of both neutrophils and eosinophils. The objective of this study was to evaluate whether theophylline modulates the neutrophil-dependent augmentation of eosinophil TBM. METHODS: Eosinophils and neutrophils were isolated from peripheral blood collected from healthy donors and were then preincubated with either 0.1 mM theophylline or the medium control. The TBM of eosinophils in response to IL-8 was evaluated in the presence or absence of neutrophils by using the chambers with a Matrigel-coated Transwell insert. The generation of O(2)(-) was evaluated by the cytochrome c reduction assay. RESULTS: As previously reported, IL-8-stimulated neutrophils significantly augmented the TBM of eosinophils. Theophylline significantly attenuated the neutrophil-dependent augmentation of eosinophil TBM (p < 0.001) and did not directly modify the TBM of neutrophils in response to IL-8 or LTB4. Similarly, the LTB4-induced TBM of eosinophils was not modified by theophylline. Finally, theophylline attenuated the superoxide anion generation from IL-8-stimulated neutrophils on the Matrigel-coated plates. CONCLUSIONS: Our results show that theophylline can attenuate the neutrophil-dependent augmentation of eosinophil TBM. This effect is possibly attributable to the suppression of neutrophil activation provoked by the combination of basement membrane and IL-8.

Evaluation of the efficiency of a new file removal system in comparison with two conventional systems.

A novel file-removal system (FRS) was designed to address weak points of conventional file-removal methods. The purpose of this study was to compare file-removal time and dentin removal rates among the FRS, the Masserann kit (Micro-Mega, Besancon, France), and an ultrasonic file-removal method. Ninety extracted mandibular incisors with separated nickel titanium files were divided into 3 groups of 30 teeth each. Groups 1, 2, and 3 had file-removal attempts made by using the Masserann kit, a CPR-7 titanium ultrasonic tip (Obtura-Spartan Corp., Fenton, MO), and the FRS, respectively. Each group had three operators removing the separated files. Pre-/postoperative digital radiographs were downloaded into image analyzing software that calculated the amount of dentin removed. The FRS needed less time and had less dentin loss than the others (p<0.05). There were statistical differences between the experienced operator and less experienced operators regarding the file-removal time and the dentin removal rates (p<0.05).

Differential effects of salbutamol and montelukast on eosinophil adhesion and superoxide anion generation.

BACKGROUND: Beta2-agonists, a representative class of bronchodilators used for asthma, have been shown to modulate some functions of eosinophils, including cell adhesion. Similarly, a leukotriene receptor antagonist (LTRA) may be beneficial in controlling inflammation in asthma, as cysteinyl leukotrienes (cysLTs) can cause accumulation or activation of eosinophils. Recent evidence suggests that the addition of an LTRA, but not a long-acting beta2-agonist, to inhaled corticosteroid additionally reduces the number of eosinophils in sputum and blood from patients with asthma. The present study examined whether a beta2-agonist and an LTRA differentially modify eosinophil adhesion and activation induced by cysLTs and other activators. METHODS: Eosinophils were isolated from blood of healthy donors and then incubated in the presence or absence of salbutamol (albuterol) or montelukast. Eosinophils were then exposed to leukotriene D4 (LTD4) or another activator, and the generation of superoxide anion (O2-) was evaluated by cytochrome C reduction assay. Eosinophil adhesion was examined by an eosinophil peroxidase assay. RESULTS: Montelukast, but not salbutamol (both at 1 microM), inhibited LTD4-induced (100 nM) eosinophil adhesion to recombinant human intercellular adhesion molecule 1. Both drugs similarly and partially inhibited the 100 pM interleukin-5-induced adhesive response of eosinophils to recombinant human intercellular adhesion molecule 1. Montelukast, but not salbutamol, blocked LTD4-induced eosinophil O2- generation of eosinophils. Finally, neither salbutamol nor montelukast modified phorbol myristate acetate (1 ng/ml)-induced O2- generation from eosinophils. CONCLUSION: These results confirm that LTD4 directly induces activation of eosinophils via the cysLT1 receptor. Furthermore, the results suggest that a beta2-agonist has no effect on eosinophil adhesion and activation induced by cysLTs. These results explain the differential effects of an LTRA and a beta2-agonist in the treatment of eosinophilic inflammation in asthma.

Eosinophil trans-basement membrane migration induced by interleukin-8 and neutrophils.

Neutrophilic inflammation observed with severe asthma is often associated with interleukin-8 (IL-8). Neutrophils can secrete a variety of mediators that may augment the migration of eosinophils. We have reported a positive correlation between the concentrations of neutrophils and eosinophils in sputum from subjects with severe asthma, suggesting a possible role of neutrophils in regulating eosinophilic inflammation. The aim of this study was to investigate whether neutrophils stimulated with IL-8 modify the trans-basement membrane migration (TBM) of eosinophils. Eosinophils and neutrophils were isolated from peripheral blood drawn from healthy donors or subjects with mild asthma. The TBM of eosinophils in response to IL-8 was evaluated in the presence or absence of neutrophils using the chambers with a Matrigel-coated transwell insert. Neither IL-8 alone nor the presence of neutrophils alone induced the TBM of eosinophils. However, when eosinophils were coincubated with neutrophils and stimulated with IL-8, the TBM of eosinophils was significantly augmented. This augmented TBM of eosinophils was inhibited by a matrix metalloproteinase-9 inhibitor, a leukotriene B4 receptor antagonist, platelet-activating factor antagonists, or an anti-TNF-alpha monoclonal antibodies. These results suggest that neutrophils migrated in response to IL-8 may lead eosinophils to accumulate in the airways of asthma and possibly aggravate this disease.

Usefulness of itraconazole for sporotrichosis in Japan: study of three cases and literature comparison of therapeutic effects before and after release on the market.

Potassium iodide, itraconazole (ITCZ), and terbinafine are widely known as oral antifungal agents for the treatment of sporotrichosis. Although potassium iodide has been used as the antifungal agent of first choice in Japan due to its high efficacy, its use is not covered by the health insurance programs. In this report, we present the disease course of 3 patients with sporotrichosis in which ITCZ was remarkably effective. By reviewing cases reported in the past, we found sufficient therapeutic effects of ITCZ against sporotrichosis. We also conducted a simple comparison of the efficacy of ITCZ in clinical trials with that of its post-market release; finding the latter to be lower. This seems to be attributable to the problem of compliance or the administration method.

Association between neutrophilic and eosinophilic inflammation in patients with severe persistent asthma.

BACKGROUND: Eosinophils are generally recognized as effector cells in asthma. Recently, neutrophils have been suggested to contribute to the development of chronic severe asthma. The mechanisms by which neutrophils contribute to the pathophysiology of asthma remain to be elucidated; however, neutrophils may affect either accumulation or functional status of eosinophils via the generation of inflammatory mediators. The objective of this study was to evaluate whether neutrophilic inflammation is associated with eosinophilic inflammation in severe asthma. METHODS: Following the inhalation of hypertonic saline, induced sputum was obtained from 12 healthy controls, 10 mild persistent asthmatics who were treated with low-dose inhaled corticosteroids, and 8 severe persistent asthmatics who were treated with combinations of drugs including high-dose inhaled corticosteroids and oral prednisolone. Subsequently, differential inflammatory cell counts were evaluated. RESULTS: The percentage of eosinophils in induced sputum was significantly higher in patients who showed airway neutrophilia. In severe persistent asthmatics, the percentage of neutrophils was significantly correlated with the percentage of eosinophils in induced sputum. CONCLUSIONS: The results of the present study suggest that accumulated neutrophils may contribute to the development of eosinophilic inflammation in severe persistent asthmatics who were treated with oral and high-dose inhaled corticosteroids. This effect may contribute to the eventual manifestation of airway inflammation in severe asthma.

Effect of the cysteinyl leukotriene antagonist pranlukast on transendothelial migration of eosinophils.

BACKGROUND: Evidence shows that leukotriene receptor antagonist (LTRA) can cause a partial reduction of eosinophils in the asthmatic airway. Although cysteinyl leukotrienes (CysLTs) can regulate the development of eosinophilic inflammation, LTRA might modulate the eosinophilic response to other inflammatory molecules involved in allergic inflammation. Montelukast is an LTRA that inhibits eosinophil transendothelial migration (TEM) in response to platelet-activating factor (PAF). The present study evaluates whether pranlukast (an LTRA) modifies eosinophil TEM in response to chemoattractants including PAF and C-C chemokines. METHODS: Eosinophils isolated from the blood of healthy individuals were incubated with or without pranlukast. We then evaluated eosinophil transmigration across human umbilical vein endothelial cells in response to LTD(4), eotaxin, RANTES and PAF. RESULTS: Pranlukast did not modify the spontaneous transmigration of eosinophils (n = 5). As reported, eosinophil TEM was significantly augmented by 0.1 microM LTD(4) and this enhancement was blocked by 1 microM pranlukast (p < 0.001; n = 6). On the other hand, pranlukast did not modify eosinophil transmigration in response to eotaxin, RANTES, or PAF (p > 0.1; n = 5). CONCLUSION: The inhibitory effect of pranlukast on eosinophil transmigration is highly specific for the CysLT1-dependent pathway.

Leukotriene D4 and eosinophil transendothelial migration, superoxide generation, and degranulation via beta2 integrin.

BACKGROUND: Evidence indicates that cysteinyl leukotriene (cysLT) 1 receptor antagonists possess anti-inflammatory properties in asthmatic patients in vivo. Although the exact mechanisms of these actions remain unknown, cysLTs regulate the locomotion and functions of eosinophils. We previously reported that leukotriene D4 augments the expression of eosinophil beta2 integrin and the adhesion of eosinophils to rh intercellular adhesion molecule 1 via beta2 integrin. OBJECTIVE: To examine whether leukotriene D4 modifies the transendothelial migration (TEM) and effector functions of eosinophils. METHODS: We evaluated the effects of leukotriene D4 on (1) eosinophil TEM across human umbilical vein endothelial cells, (2) superoxide anion (O2-) generation, and (3) eosinophil-derived neurotoxin release in eosinophils isolated from the blood of healthy individuals. RESULTS: Leukotriene D4 (0.1-1 microM) significantly induced eosinophil TEM, O2- generation, and eosinophil-derived neurotoxin release. Pranlukast, a cysLT1 receptor antagonist, significantly inhibited all of these parameters, although the inhibitory effect on O2- generation was partial. All of these responses were significantly inhibited by anti-beta2 integrin but not by anti-alpha4 integrin antibodies. CONCLUSIONS: Leukotriene D4 directly up-regulates the TEM and effector functions of eosinophils mainly via the cysLT1 receptor and beta2 integrin. These effects of leukotriene D4 probably contribute to the manifestation of eosinophil inflammation in asthmatic airways.

Immunotherapy attenuates eosinophil transendothelial migration induced by the supernatants of antigen-stimulated mononuclear cells from atopic asthmatics.

BACKGROUND: Eosinophil transendothelilal migration across vascular endothelial cells is an initial step of eosinophil accumulation in allergic inflammation. There is increasing evidence that specific immunotherapy (SIT) modulates the production of inflammatory molecules from mononuclear cells. OBJECTIVE: The present study was undertaken to examine whether SIT modifies eosinophil transendothelial migration induced by the supernatants of antigen-stimulated mononuclear cells from atopic asthmatics. METHODS: Dermatophagoides farinae (Df)-sensitive mild persistent asthmatics were divided into a SIT-treated group and a control group. Peripheral blood mononuclear cells (PBMC) were isolated before and after SIT using the rush protocol, and cultured for 96 h at 37 degrees C in the presence or absence of Df antigen. Eosinophils were isolated from the blood of healthy subjects, and put on transwell filters coated with pulmonary microvascular endothelial cell monolayers stimulated with IL-4 plus TNF-alpha. The supernatants of PBMC were applied to the lower compartment and the transmigration of eosinophils was examined. RESULTS: Df stimulation of PBMC resulted in an augmentation of eosinophil transendothelial migration. This enhancement was abrogated following SIT. In the control group, the antigen-induced effect on eosinophil transmigration did not show an interval change. CONCLUSION: SIT attenuates eosinophil transendothelial migration induced by antigen-stimulated mononuclear cells.

[Clinical analysis of 22 cases with syphilis racenta in Department of Dermatology, Nippon Medical School].

Forty-nine patients with syphilis were seen from January 1996, to June 2000 at the Dermatological Clinic of Nippon Medical School Hospital. The frequency of syphilis among all outpatients was 0.17%, and the number of male syphilis patients was almost twice that of female syphilis patients. Many sexual contacts (especially with female prostitutes) were considered to be the source of the infection in a large proportion of the syphilis patients. Chancres were observed in 50% of the 6 patients with primary syphilis. Macular or papular syphilide and psoriasis syphilitica were the most frequently observed symptoms in the patients with secondary syphilis. The Jarisch-Herxheimer reaction was observed in 18.8%. The titer of IgM-TPHA responded well to the therapy, and decreased or even disappeared after treatment. The titer of TPHA did not change markedly upon treatment. A retrospective study of syphilis from 1980 revealed that the incidence of syphilis, especially early infectious syphilis, in patients at our clinic has decreased markedly since 1991.

Theophylline attenuates the adhesion of eosinophils to endothelial cells.

BACKGROUND: Bronchial asthma is characterized by infiltration of eosinophils and other inflammatory cells into the airways. Binding to adhesion molecules expressed on endothelial cells is an initial step of eosinophil accumulation in the airways of asthmatic patients. Theophylline has been widely used in the treatment of bronchial asthma mainly due to its bronchodilating effect. It has recently been suggested that theophylline induces modulating effects on the survival or functional status of eosinophils. The objective of this study was to determine whether theophylline modifies the adhesive interaction between eosinophils and endothelial cells. METHODS: Eosinophils were isolated from blood of patients with mild asthma. The effects of theophylline on eosinophil adhesion to human umbilical vein endothelial cells (HUVEC) or recombinant adhesion proteins were evaluated. The effect of theophylline on the expression of adhesion molecules on HUVEC was also examined. RESULTS: Theophylline significantly inhibited the eosinophil adhesion induced by formyl-methionyl-leucil-phenylalanine (FMLP) or interleukine-5 (IL-5) at a concentration within the therapeutic range. The effect of theophylline on eosinophil adhesion was mimicked by rolipram, a selective phosphodiesterase inhibitor, and N6,2'-O-dibutyladenosine 3'5'-cyclic monophosphate (Db-cAMP; cAMP analogue). Finally, theophylline inhibited the expression of ICAM-1 and VCAM-1 on HUVEC stimulated with IL-4 plus TNF-alpha. CONCLUSION: Theophylline showed inhibitory effects on both the adhesive property of eosinophils and the expression of adhesion molecules on endothelial cells, thus suggesting that theophylline attenuates the adhesive interaction between eosinophils and endothelial cells.

An experimental study on the vasoconstriction effect of calcium hydroxide using rat mesentery.

Calcium hyroxide has been used for eliminating persistent intracanal exudation. In order to address the mechanism behind this action, we investigated whether calcium hydroxide solutions cause the constriction of microvessels in the mesenteric microcirculation bed of rats. The exteriorised mesentery from anaesthetised rats was spread in a chamber, and arterioles, venules and capillaries were viewed under a digital microscope. Various concentrations of calcium hydroxide solutions were applied for 10 sec, and the diameter of the microvessels was recorded. In arterioles, calcium hydroxide solutions caused rapid and transient constriction. A statistically significant difference versus original diameter was detected 1 min after the application of 4.0 x 10(-3) mol/l and 1.0 x 10(-2) mol/l solutions (p < 0.05, one-way analysis of variance and Tukey-Kramer test). No statistically significant constriction occurred in capillaries and venules. It was concluded that the arteriolar constriction might be an explanation for the exudation-controlling effect of intracanal calcium hyroxide dressings.