COVID-19 preventive behaviours among people with anxiety and depressive symptoms: findings from Japan.

OBJECTIVES: The aim of the study was to examine COVID-19 preventive behaviours among individuals with mental health problems. STUDY DESIGN: This is a pooled cross-sectional study. METHODS: Online survey data were analysed from 2000 Japanese adults collected in April and May 2020. Information was obtained on 13 COVID-19 preventive behaviours and anxiety and depressive symptoms using the Generalized Anxiety Disorder 7-item scale and Patient Health Questionnaire-9, respectively. Linear regression analysis was used to examine the associations. RESULTS: In models adjusted for demographic and socio-economic factors, anxiety (coefficient: -0.77, 95% confidence interval [CI]: -1.30, -0.24) and depressive symptoms (coefficient: -0.82, 95% CI: -1.34, -0.30) were both associated with significantly lower engagement in COVID-19 preventive behaviours. CONCLUSION: Our results highlight the importance of facilitating the performance of preventive behaviours in individuals with mental health problems to prevent the spread of COVID-19 in this population.

Pituitary adenylate cyclase-activating polypeptide promotes eccrine gland sweat secretion.

BACKGROUND: Sweat secretion is the major function of eccrine sweat glands; when this process is disturbed (paridrosis), serious skin problems can arise. To elucidate the causes of paridrosis, an improved understanding of the regulation, mechanisms and factors underlying sweat production is required. Pituitary adenylate cyclase-activating polypeptide (PACAP) exhibits pleiotropic functions that are mediated via its receptors [PACAP-specific receptor (PAC1R), vasoactive intestinal peptide (VIP) receptor type 1 (VPAC1R) and VPAC2R]. Although some studies have suggested a role for PACAP in the skin and several exocrine glands, the effects of PACAP on the process of eccrine sweat secretion have not been examined. OBJECTIVES: To investigate the effect of PACAP on eccrine sweat secretion. METHODS: Reverse transcriptase-polymerase chain reaction and immunostaining were used to determine the expression and localization of PACAP and its receptors in mouse and human eccrine sweat glands. We injected PACAP subcutaneously into the footpads of mice and used the starch-iodine test to visualize sweat-secreting glands. RESULTS: Immunostaining showed PACAP and PAC1R expression by secretory cells from mouse and human sweat glands. PACAP immunoreactivity was also localized in nerve fibres around eccrine sweat glands. PACAP significantly promoted sweat secretion at the injection site, and this could be blocked by the PAC1R-antagonist PACAP6-38. VIP, an agonist of VPAC1R and VPAC2R, failed to induce sweat secretion. CONCLUSIONS: This is the first report demonstrating that PACAP may play a crucial role in sweat secretion via its action on PAC1R located in eccrine sweat glands. The mechanisms underlying the role of PACAP in sweat secretion may provide new therapeutic options to combat sweating disorders.

Compound heterozygotes for filaggrin gene mutations do not always show severe atopic dermatitis.

BACKGROUND: Mutations in FLG, which encodes profilaggrin, cause ichthyosis vulgaris (IV) and are an important predisposing factor for atopic dermatitis (AD). IV shows autosomal hemidominant (semidominant) inheritance, and patients with bi-allelic FLG mutations tend to have severe IV phenotypes. However, the effect of bi-allelic FLG mutations on AD incidence and severity remains a subject of controversy. OBJECTIVE: In this study, we studied individuals with bi-allelic null FLG mutations to elucidate the effect of bi-allelic FLG mutations on AD incidence and severity. METHODS: Six individuals with bi-allelic FLG null mutations from three families of IV/AD were investigated. We report the detailed clinical features of the individuals. The phenotype was confirmed by the clinical examinations and the severity of IV and AD was scored using ichthyosis score and Eczema Area and Severity Index (EASI). RESULT: It was found that five of the six patients had severe IV, and the remaining patient showed moderate IV. Two of the six had moderate AD and three of the six had mild AD. The remaining patient had no AD. CONCLUSION: Our results suggest that individuals with bi-allelic FLG mutations do not always have severe AD and confirm that not all individuals with bi-allelic FLG mutations have AD.

Utility of patch testing for patients with drug eruption.

BACKGROUND: Patch testing is less dangerous than oral provocation testing for identification of the causative drug for patients with drug eruption; however, its usefulness for such identification is controversial. AIM: To clarify the rates of positive patch testing for patients with drug eruption, classified by causative drugs and clinical features. METHODS: We analysed results during the period 1990-2010 for 444 patients (151 men, 293 women; mean ± SD age 49.9 ± 18.6 years) who were tested for drug eruption. In the patient group, there were 309 people (69.1%) with maculopapular eruption and 31 (6.9%) with severe drug eruption. The test materials were applied to the back and left for 2 days under occlusion, then results were assessed by the International Contact Dermatitis Research Group (ICDRG) scoring system 3 days after application. Reactions of + to +++ were regarded as positive. RESULTS: Of the 444 patients, 100 (22.4%) had a positive patch test result to a suspected drug. Positive rates were 23.6% and 20.0% for maculopapular eruption and fixed drug eruption, respectively. The class of materials to which most patients reacted positively was contrast medium (n = 53; 41.1%), followed by drugs acting on the central nervous system (n = 18; 28.6%). In the latter group, 16 of the 18 patients were positive to antiepileptics. CONCLUSIONS: Positive rates depend on the causative drug rather than the clinical features of the drug eruption. Patch testing is useful when contrast medium or antiepileptics are suspected to be the causative drugs. However, standardization of patch test materials and method of reading is needed, as well as guidelines regarding when testing should be performed. Although patch testing for drug eruption has significant potential, it requires further validation.

Repeated episodes of fixed eruption 3 months after discontinuing pegylated interferon-alpha-2b plus ribavirin combination therapy in a patient with chronic hepatitis C virus infection.

We report a 73-year-old man who developed repeated episodes of erythematous, bullous plaques beginning 3 months after discontinuation of combination treatment with pegylated interferon (IFN)-alpha-2b and ribavirin for hepatitis C virus infection. The first episode resolved within a week without treatment, but the lesions recurred about once a month and were associated with high fever. Physical examination found darkly reddish, pigeon-egg-sized erythematous plaques with occasional flaccid blisters, predominantly on the trunk and proximal limbs, lip and penis. Histological examination showed well-demarcated foci of full-thickness epidermal necrosis and exocytosis of lymphoid cells. Pegylated IFN-alpha2b and ribavirin produced no response in lymphocyte stimulation tests. Systemic prednisolone led to rapid healing of skin lesions at the time of the fifth episode, leaving pigmented macules, but lesions recurred at the same sites within weeks of discontinuation of this treatment. It is uncertain whether this case represented a prolonged drug rash provoked by pegylated IFN-alpha2b or a fixed eruption in response to another antigen.

Effects of oral administration of ciclosporin A on skin carcinogenesis: a study using the two-stage carcinogenesis protocol in mice.

BACKGROUND: Development of malignant skin neoplasms in patients receiving cyclosporin A (CsA) has been reported. The relationship between the pathogenesis of skin carcinogenesis and the dose of CsA is still unclear. AIM: To clarify the effect of oral administration of CsA, especially its dose, on skin carcinogenesis. METHODS: Hr-1 hairless mice were assigned to the following four groups: (i) control group (n = 8), given vehicle intragastrically six times/week and acetone applied to the skin of the back; (ii) chemical-alone (n = 11), given vehicle intragastrically + application of 7,12-dimethylbenz[a]anthracene (DMBA) once week and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) twice week to the back; (iii) CsA-alone group (n = 8), given CsA intragastrically (10 mg/kg) six times/week and vehicle applied to the back twice week; and (iv) CsA + chemical group (n = 8), given 10 mg/kg CsA intragastrically + topical DMBA and TPA. The number of papules > 3 mm in diameter that had developed on the back after 15 weeks was counted. The mean epidermal thickness and number of dermal infiltrates were determined. The same experiments were performed using CsA at doses of 5 and 20 mg/kg. RESULTS: Oral administration of either 10 or 20 mg/kg CsA significantly enhanced the formation of papillomas by DMBA and TPA, but no enhancement was observed when 5 mg/kg CsA was administered. The mean epidermal thickness and number of dermal infiltrates were significantly greater in the CsA + chemical group than in the chemical-alone group. CONCLUSION: These data suggest that oral administration of CsA in excess of a certain dose can accelerate tumour development in mice.

Computer-assisted three-dimensional reconstruction of human dermal dendrocytes.

We attempted to characterize the three-dimensional structure of dermal dendrocytes and to clarify the spatial relationships between dermal dendrocytes and mast cells, macrophages, and nerves. Normal human adult skin (breast, n = 2) was routinely processed for electron microscopy. Every other section (about 50 per data set) was collected at 80-nm intervals traversing about 8 microns of tissue. Grids showing the same cells were photographed by electron microscopy at a magnification of 4000x. Based on the 10-20 photographs per data set, cell outlines were digitized into the reconstruction program at appropriate layers and aligned. Thin, elongated cytoplasmic "dendrites" of dermal dendrocytes in two-dimensional micrographs proved to be thin, membrane-bound flaps in three-dimensional reconstruction. For dermal dendrocytes concentrated about superficial vessels (perivascular dendrocytes), the flaps enshrouded the vessel wall, and for dermal dendrocytes directly beneath the epidermis (subepidermal dendrocytes), these flaps were aligned parallel to the dermal-epidermal junction. The three-dimensional feature of dermal dendrocytes (perivascular and subepidermal) is quite similar to that of perivascular adventitial veil cells, suggesting ultrastructurally identified perivascular dendrocytes and veil cells must be identical cells. In conventional ultrathin sections, 20-40% of perivascular dendrocytes and occasional subepidermal dendrocytes were closely associated with mast cells. When viewed by computer-assisted three-dimensional reconstruction, membrane flaps of dermal dendrocytes consistently shrouded mast cell membranes for 50-90% of their perimeter; mast cells resembled a ball in a baseball glove (dermal dendrocytes). Occasional dermal dendrocytes surrounded non-myelinated nerves in the superficial dermis. Membrane flaps also enabled dermal dendrocytes to present extensive areas to the plasma membranes of adjacent monocyte/macrophages. These findings indicate that dermal dendrocytes are non-dendritic cells that are spatially related to mast cells, monocyte/macrophages, microvessels, and nerves by their membranous flaps. This suggests the need for further study of functional interactions between these cells.

Role of mast cells in early epithelial target cell injury in experimental acute graft-versus-host disease.

The skin is a major target organ for graft-versus-host disease (GVHD), the principal complication of allogeneic bone marrow transplantation. The purpose of the present study was to test whether mast cell degranulation might be related to early target cell injury in the development of acute GVHD. We employed two irradiated murine strain combinations, one in which disease was mediated by CD4+ effector T cells (B10.D2-->DBA/2), and the other by CD8+ effector T cells (B10.BR-->CBA). As compared to controls, both models exhibited mast cell degranulation of differing extents and patterns, as well as dyskeratosis in the epidermis before the influx of effector lymphocytes. These results suggested that factors produced and released by degranulated dermal mast cells might contribute to early target cell injury. Accordingly, the possible role of tumor necrosis factor (TNF)-alpha, a cytokine recently discovered in mast cell granules, was investigated by the injection of anti-TNF-alpha antibody during the course of disease mediated by either CD4+ or CD8+ T cells. Although overall survival of recipients undergoing CD4+ T-cell-mediated GVHD was only slightly improved and the extent of mast cell degranulation was not affected by anti-TNF-alpha antibody treatment, the skin exhibited a significant diminution in the number of dyskeratotic cells/linear mm at 3-4 weeks post-transplantation. In contrast, anti-TNF-alpha antibody failed to enhance survival or reduce the number of dyskeratotic cells in the skin during CD8+ T-cell-mediated disease. Finally, to determine whether CD8+ T-cell-mediated GVHD was at all dependent upon mast cell involvement, the C3H.SW-->B6WWv strain combination was utilized, in which recipients were genetically deficient in mast cells. Onset of GVHD was significantly delayed in B6WWv mice and was clearly correlated to the appearance and increase of de novo mast cells at later time points.

Antigenic characterization in ampiroxicam-induced photosensitivity using an in vivo model of contact hypersensitivity.

Ampiroxicam (APX), a prodrug of piroxicam (PXM), has been reported to induce photosensitivity. Antigenic characterization of these photosensitivities, however, is still insufficient. The purpose of the present study was to elucidate further mechanism of photosenstivity induced by APX and PXM using an in vivo model of contact hypersensitivity in guinea pigs. Animals sensitized with ultraviolet-A (UVA)-irradiated 1% APX showed positive reaction in the patch testing to UVA-irradiated 1% APX and 1% thiosalicylate (TOS), while they were negative in challenge with UVA-irradiated 1% PXM, non-irradiated APX and PXM, whereas none of UVA-irradiated or non-irradiated APX and PXM showed positive patch test reaction in animals sensitized with UVA-irradiated 1% PXM or control vehicles. Animals sensitized with 1% TOS were successfully challenged by 1% TOS and cross-reacted with UVA-irradiated 1% APX; however, they failed to react with UVA-irradiated PXM, non-irradiated APX and PXM. Indeed, the in vitro study revealed that the concentration of APX was easily reduced by the increase of UVA irradiation dose, as compared with that of PXM. Interestingly, absorption spectrum of UVA-irradiated APX was similar to that of TOS, which is thought to be an active hapten of PXM. In the present study, we succeeded in the development of a novel animal model reflecting the clinical observations. Furthermore, these results suggested that contact hypersensitivity induced by UVA-irradiated APX is developed by photoproducts of APX itself, but not by the biotransformation of APX to PXM.

Hairless guinea pig skin: anatomical basis for studies of cutaneous biology.

In order to characterize the microscopic anatomy of hairless guinea pig (HL-GP) skin, we utilized light microscopy with a computer-assisted image analysis system, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). SEM revealed that the hair shafts of HL-GPs were thin, short, extremely irregular in diameter and often twisted and curled. The HL-GP epidermis was of similar thickness to that of human skin with distinct strata, serrated/non-serrated basal keratinocytes and shallow dermal papillae. The density of Langerhans cells in epidermal sheets, visualized by adenosine-s-triphosphatase staining, was similar to that of normal-haired guinea pigs (HD-GPs), although the dendrites of HL-GPs were thicker and shorter than those of HD-GPs. The dermal vasculature of HL-GPs was well-developed and similar to that of humans, demonstrating a network of vertically oriented capillary loops. HL-GPs had significantly more dendritic or spindle-shaped dermal interstitial cells than humans and HD-GPs. Collectively, these data suggest that HL-GP skin is more similar to human skin than to the skin of HD-GPs and other rodents and, therefore, the HL-GP may be a useful animal for studying cutaneous biology, experimental pathology, pharmacology and toxicology.

Simultaneous development of insulin dependent diabetes mellitus and alopecia areata universalis.

Alopecia areata universalis developed gradually over nine months in a 25-year-old woman. When her scalp hairs were totally lost and other body hair began to fall out, the symptoms of insulin dependent diabetes mellitus, an organ-specific autoimmune disease, developed rapidly and progressed to diabetic coma. Alopecia did not regress after the metabolic state improved following insulin therapy. Biopsy of the scalp skin revealed significant reduction of the total number of hair bulbs and prominent lymphocyte infiltration into the remaining hair follicles. Insulin dependent diabetes mellitus and alopecia areata universalis are both thought to be related to the autoimmune mechanism and sometimes coexist. However, simultaneous development of these two disorders is extremely rare.

Glycosylated proteins of skin, nail and hair: application as an index for long-term control of diabetes mellitus.

The purpose of the present study was to compare the degrees of nonenzymatically glycosylated proteins in the skin (stratum corneum), the nail, the hair, and hemoglobin obtained simultaneously from the same subject and to evaluate the most useful sample for management of diabetic complications. Fifty-one diabetic patients and 20 control patients were examined, utilizing furosine determination. Furosine value of the skin in diabetics was 2.14 +/- 1.70%, whereas that in controls was 1.65 +/- 0.47%. Furosine value of the nail in diabetics was 6.67 +/- 3.30%, whereas that in controls was 4.16 +/- 1.62%. Furosine value of the hair in diabetics was 1.30 +/- 1.11%, whereas that in controls was 1.29 +/- 1.71%. Close correlations were detected between HbA1 (glycosylated hemoglobin) and furosine of the nail (r = 0.58, p less than 0.001), HbA1 and furosine of the skin (r = 0.48, p less than 0.001), and HbA1 and furosine of the hair (r = 0.43, p less than 0.01); however, poor correlations were found between furosine of the hair and the skin (r = 0.35, p less than 0.05) and furosine of the nail and the hair (r = 0.33, p less than 0.05). Furosine of the nail was significantly correlated with the FBS (fasting blood sugar) of the same time, previous 6, and previous 12 months. Furosine value of the nail, we believe, is the most useful indicator for evaluating long term control of diabetics and may provide useful information for management of diabetic complications.

Flame figures associated with bullous pemphigoid.

We report a case of bullous pemphigoid showing the histological features of flame figures. An 80-year-old man was admitted with multiple, tense, thumb-sized blisters among erythematous plaques on his trunk and limbs. A biopsy showed accumulations of eosinophil granules on the collagen fibers, forming characteristic "flame figures", in addition to the features of bullous pemphigoid. We retrospectively examined biopsy specimens from 34 patients with bullous pemphigoid treated in our department over the last 10 years for the presence of flame figures. They were observed in 3 of these patients (8.8%), all of whom were more than 80 years of age. Our retrospective study indicates that the association of flame figures with bullous pemphigoid is not rare, considering the fact that the present case is only the third report of this association. Our data also suggest that the degree of dermal eosinophilia and the formation of flame figures could be related.

Safe pleural contraction employing a new tip for electrosurgical units. An ex vivo experiment.

BACKGROUND: Certain pulmonary lesions are treated by lung tissue contraction induced by heat administered by laser or electrosurgical unit (ES). ESs are comparatively less expensive, less complicated and more ubiquitous than a lasers but with their conventional tip carries the a risk of damaging the pleura. We developed a large ball tip (M-tip) for ES and evaluated its effect on the pleura in comparison with that of Nd:YAG laser in ex vivo lung. METHOD: We employed lobes obtained through surgical resection. Using the Nd:YAG laser, the lung was irradiated for 2 seconds at levels of 5, 10 and 20 watts (10, 20 and 40 Joules). Using the M-tip ES, the pleura received treatment at levels of 10, 20 and 40 watts for 2 seconds (20, 40 and 80 Joules) in spray coagulation mode. Upon completion of these procedures, 144 tissue specimens obtained from 24 lobes were examined under light microscopy. RESULTS: Upon the application of Nd:YAG at 20 Joules, 22 (92%) of 24 visceral pleura demonstrated amorphous degeneration. With the application of ES at 40 Joules watts, 24 (100%) samples examined demonstrated amorphous degeneration (P = 0.47). Of the samples where pleural destruction was evident (Nd:YAG; 40 Joules, ES; 80 Joules), an accompanying air leak pattern (pleural destruction associated with slight parenchymal contraction) was observed in 5 (21%) of the samples treated with Nd:YAG and in 10 (42%) of those treated with the M-tip ES (p = 0.12). CONCLUSION: The M-tip ES induced proper contraction of the pleura with relatively little destructive damage to the pleura at 40 Joules. Accordingly, it may be possible to induce pleural contraction using this new device with the same degree of safely that the Nd:YAG laser provides.

Intrapulmonary mature teratoma.

Intrapulmonary teratoma is reported in a 22-year-old male. A chest X-ray in a physical examination showed a round shadow in the left hilum of a 22-year-old man who, on admission, reported slight malaise and a decrease in body weight. Computed tomographic scan and magnetic resonance imaging of the chest showed a heterogeneously dense cystic lesion. The preoperative diagnosis was anterior mediastinal teratoma, and the tumor was located in the anterior segment of the left upper lobe after thoracotomy. Segmentectomy of the left upper division showed a 4.0 x 3.5 cm tumor diagnosed as an intrapulmonary mature teratoma--the 27th such case reported in the English-language literature. This is, to the best of our knowledge, the first intrapulmonary teratoma involving magnetic resonance imaging.

Unsuspected lung cancer accompanied by catamenial pneumothorax.

A 45-year-old nonsmoking woman with repeated coughing and dyspnea on effort was admitted to our hospital diagnosed with right-sided pneumothorax on chest X-ray. Chest computed tomography showed neither bullae nor nodules. Chest drainage failed to completely reexpand the lung, necessitating video-assisted thoracic surgery. Thoracoscopy showed pleural thickening in the apical segment without bullae or air leakage, dark-brown pigmentation of the diaphragm, and an unsuspected small nodule about 5 mm in diameter on the diaphragmatic surface of the right lower lobe. Pneumothorax was treated by mechanical abrasion of parietal pleura and upper lobe wedge resection. The lower lobe and nodule were wedge-resected using staplers. The nodule was bronchioloalveolar carcinoma of Noguchi's type B. To improve curability and check for diaphragmatic lesions, right posterolateral thoracotomy was conducted on post-video-assisted thoracic surgery day 28. Aggressive intraoperative lymph node exploration yielded no remarkable histological findings. Nonanatomical lower lobe wedge resection was done and the diaphragm with pinhole-like perforations was partially resected. The resected lung showed no cancerous tissue. Endometrial tissue was histologically confirmed in the resected diaphragm. The patient has remained asymptomatic in 14-month follow-up. This is, to our knowledge, the first lung cancer accompanied by catamenial pneumothorax.

[The role of surgery for chronic empyema of the advanced ages].

Chronic empyema, a sequelae of pulmonary tuberculosis, is now a only tuberculosis-related disease which was remained to be treated surgically. The candidates who have basically poor respiratory function are now attained advanced age. Over a 15 years period (1980-95), 22 patients 70 years of age or older underwent surgical intervention for chronic empyema at our hospital. There were 17 men and 5 women, ranging from 70 to 80 years of age (median age 75.0). They were 15.3% of all 145 surgically treated patients during same period. The empyema continued latent from 25 to 58 years (average 39.8 years). On admission they complained of productive cough (9), fever (9), hemosputam (5) and mass on the chest wall. Their Hugh-Johnes classification for dyspnea was I.: 4, II.: 6, III.: 11, IV.: 1 respectively. Their %VC ranged from 31.5 to 79.0 (average 54.8). In fifteen patients, tubercle bacilli (5), aspergillus (3) and other bacteria (9) were discovered in the empyema space. Surgical procedures consisted of 1 pneumonectomy (4.5%), 12 decortication or curettage of empyema wall (54.5%), 4 extraperiosteal air plombage (18%) and 5 other procedures (muscle or omental plombage, thoracoplasty, fenestration and others) (22.7%). There were no operative death and no lethal postoperative complication. In contrast, lethal postoperative complications such as GVIID, MOF and gastrointestinal bleeding occurred in the younger group. There were 2 cases of late respiratory failure in 70 years or older and 6 cases in younger group. Seventy-four years man who, preoperative %VC 33.0, underwent pneumonectomy died of asphyxia 6 month postoperatively. Another 74 years man who, preoperative %VC 76.1, developed respiratory failure after relapse of pulmonary tuberculosis. Four patients of younger group who developed late respiratory failure had all received thoracoplasty as a second operation. Other 2 patients, preoperative %VC 33.0 and 27.4 respectively, had undergone pneumonectomy. The risk of lethal postoperative complication or late respiratory failure were dependent mainly on preoperative respiratory function or surgical procedure selected rather than the age of patients.

[Two cases of metastasizing benign leiomyomatosis from myoma uteri].

Case 1. A 50-year-old woman was referred to our hospital because of multiple bilateral small round lesion on chest radiography. She had undergone total hysterectomy for myoma uteri at the age of 33. She underwent thoracoscopic tumor excision at left lung. The lesion was proved benign. Right side lesions were laterly excised using thoracotomy. Case 2. A 49-year-old woman was referred to us because of two ovoid lesion at left lung area of chest radiography. She also had undergone total hysterectomy for myoma uteri at the age of 37. She underwent tumor extirpation using thoracotomy. All samples of two patients revealed, pathologically, lesions were consisted of benign spindle-like calls similar to those of myoma uteri. Therefore, we consider these lesions were pulmonary metastasis of myoma uteri. Myoma uteri has certain potential of metastasizing to the lung, in spite of benign disease.