Clinical characteristics and factors related to antibiotic-associated diarrhea in elderly patients with pneumonia: a retrospective cohort study.

BACKGROUND: Antibiotic-associated diarrhea (AAD) is a common problem among elderly inpatients because many elderly patients are admitted for pneumonia or other conditions that necessitate antibiotic treatment. In the super aging population, more patients are suffering from pneumonia than before, but the incidence or risk factors for AAD among many elderly patients have not been well scrutinized. METHODS: We conducted a retrospective cohort study of elderly patients diagnosed with pneumonia from April 2014 to March 2019 who were admitted to the Department of General Medicine of a Tertiary Care Hospital in Japan. Patients (≥ 65 years of age) who were diagnosed with bacterial pneumonia or aspiration pneumonia and treated with antibiotics were included. We defined AAD by diarrhea with more than three loose or watery stools per day and included patients who had these symptoms for either one day or two or more consecutive days. We also assessed the length of hospital stay and in-hospital mortality. The potential risk factors for AAD included age, sex, body weight, body mass index, smoking, alcohol, activities of daily living (ADL),　comorbidities, vital signs, laboratories, the severity of pneumonia, antibiotic and other medication use. RESULTS: There were 1,067 patients, the mean age was 83 years, and men accounted for 59 %. ß-Lactamase inhibitors were frequently prescribed antibiotics in 703 patients (66 %), and proton pump inhibitors (PPIs) were also commonly administered (48 %). AAD developed in 322 patients (30 %). The multivariate logistic regression model showed that ß-lactamase inhibitors (OR 1.43, 95 % CI 1.05-1.95) and PPIs (OR 1.37, 95 % CI 1.03-1.83) were associated with AAD as well as age (OR 1.03 per year, 95 % CI 1.01-1.05). CONCLUSIONS: AAD was common among elderly inpatients with pneumonia, and ß-lactamase inhibitors and PPIs were associated with AAD. Strict use of such medication should be considered to decrease the risk of AAD.

Steroid Resistant Hypereosinophilic Syndrome Suspected to Be Caused by Aberrant T-cell Subset.

A 53-year-old male presented with cough, skin rash and lymphadenopathies complicated with hypereosinophilia (HE) in the blood, and patchy shadows in both lungs on chest computed tomography. Reactive causes for HE were excluded, and no clinical or laboratory features of myeloproliferative disorders could be found. HE caused by aberrant T-cell subsets was suspected because of serum hyper-immunoglobulin E level, and organ involvement of skin and lungs, though we could show neither aberrant T-cell surface markers nor T-cell receptor gene rearrangement. In the course of steroid monotherapy, tolerable maintenance dose could not be attained and the steroid-sparing agents of hydroxycarbamide, cyclosporine and interferon-α were introduced. However, the therapeutic response was inadequate, and organ involvement of lungs and intestinal tract developed. HE caused by aberrant T-cell subsets has steroid resistance and a risk of malignant transition, and we considered this progressive steroid refractoriness to be a sign of such a transition. Cytotoxic chemotherapy or bone marrow transplantation will likely be the next treatment modality in this patient.

Severity of disease, rather than xerosis, correlates with pruritus in patients with atopic dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing skin disease characterized by xerosis and pruritus. As pruritus is an unpleasant sensation and the associated scratching aggravates the skin eruption considerably, it is important to control this symptom when treating AD. Dry skin is generally considered to be a potential cause of pruritus in xerotic skin diseases, but a clear correlation between pruritus and atopic xerosis has not been demonstrated. Aim To examine the contribution of atopic xerosis to the development of pruritus in AD. METHODS: Twenty-two patients with AD (12 males and 10 females; mean age, 27.5 years) were examined. Xerosis and the severity of disease were evaluated using the Objective Severity Assessment of Atopic Dermatitis (OSAAD) and the SCORing Atopic Dermatitis (SCORAD) index, respectively. A modified SCORAD index was calculated by removing the symptoms potentially associated with pruritus (intensity of itching and insomnia) from the standard SCORAD index. Pruritus was evaluated using both a visual analog scale and the Verbal Itch Score. RESULTS: The severity of AD (modified SCORAD index) correlated better than atopic xerosis (OSAAD score) with both pruritus scores, possibly indicating that the use of appropriate anti-inflammatory agents may be helpful in controlling pruritus as well as skin eruption in AD. CONCLUSION: Our data suggest that the severity of disease (or skin inflammation) provides a greater contribution than xerosis to the development of pruritus in AD.

Association of clinical findings in Yusho patients with serum concentrations of polychlorinated biphenyls, polychlorinated quarterphenyls and 2,3,4,7,8-pentachlorodibenzofuran more than 30 years after the poisoning event.

BACKGROUND: The Yusho poisoning incident, which was caused by rice bran oil contaminated with polychlorinated biphenyls (PCBs), polychlorinated quarterphenyls (PCQs) and polychlorinated dibenzofurans (PCDFs) generated by heat denaturation of PCB, occurred in 1968 in western Japan. Annual physical, dermatological, dental, ophthalmological and laboratory examinations were conducted for Yusho patients after the incident. From 2001, blood levels of individual PCDF congeners were also measured. The blood levels of 2,3,4,7,8-pentachlorodibenzofuran (2,3,4,7,8-PeCDF), PCBs and PCQs in Yusho patients were found to be significantly higher than those of the general population. We investigated the relationships between blood concentrations of 2,3,4,7,8-PeCDF, PCBs and PCQs in Yusho patients and the items measured in the annual medical examination. METHODS: Medical and laboratory examination data from 501 Yusho patients enrolled in the study from 2001 to 2004 were analyzed. The relationships between blood 2,3,4,7,8-PeCDF, PCB and PCQ concentrations and medical/laboratory examination data were investigated using principal components and logistic regression analyses. RESULTS: Serum Concentrations of 2,3,4,7,8-PeCDF, PCBs and PCQs in blood tended to correlate with either acneform eruptions, black comedones, cutaneous and mucosal pigmentation, and hypersecretion of meibomian glands as well as general fatigue, headaches, cough/sputum, abdominal pain, arthralgia, increased blood sugar, increased serum gamma-GTP and decreased total bilirubin. The majority of these signs and symptoms are included in the diagnostic criteria for Yusho. CONCLUSION: After Yusho patients had suffered chronic exposure to these chlorinated compounds for more than 35 years, the serum concentration of 2,3,4,7,8-PeCDF in blood was significantly related to arthralgia and decreased albumin/globulin (A/G) ratio; the serum concentration of PCBs was significantly related to ophthalmologic symptoms; and the serum concentration of PCQ to increased total cholesterol. These findings suggest that the co-contaminants may affect other functions than those originally associated with Yusho.

Association factors for atopic dermatitis in nursery school children in Ishigaki islands - Kyushu University Ishigaki Atopic Dermatitis Study (KIDS).

Atopic dermatitis (AD) is a multifactorial disease that usually decreases the quality of life of affected patients. The purpose of this study was to evaluate the associated factors for atopic dermatitis, asthma, rhinitis, and food allergy by physical examination of the skin and a questionnaire in nursery school children in Ishigaki Island, Okinawa, Japan. Enrolled in this study were 460 children from 0 to 6 years of age. Physical examination of skin symptoms and blood tests were performed. Information on past history and family history of atopic dermatitis, asthma, rhinitis, and food allergy were collected by questionnaire. The prevalence of atopic dermatitis was 12.2% (56/460). The cumulative prevalence of asthma, rhinitis, and food allergy was 19.9% (91/458), 3.3% (15/457), and 5.5% (25/456), respectively. In multivariate analysis, maternal history of rhinitis, atopic dermatitis siblings, past history of asthma and food allergy, and elevation of total IgE were significantly related to atopic dermatitis. A high total IgE level was a strong risk factor specific for atopic dermatitis in this population.

Thymus and activation regulated chemokines in children with atopic dermatitis: Kyushu University Ishigaki Atopic Dermatitis Study (KIDS).

The purpose of this population-based study was to investigate the clinical significance of serum thymus and activation-regulated chemokine (TARC) in children with atopic dermatitis (AD). Between 2003 and 2004, 1359 Japanese children aged 5 years and under were prospectively followed. Serum levels of TARC by using an ELISA in each child were monitored throughout the study period. The first tested year, the mean serum level of TARC in children with sustained AD (mean; 691.7 pg/mL) was significantly higher than that of regressed AD children (569.9 pg/mL), newly developed AD children (380.1 pg/ mL), and healthy children (506.3 pg/mL). The changes of TARC levels in sustained AD children found no significance between 2003 (691.7 pg/mL) and 2004 (682.0 pg/mL). The mean levels of TARC of both regressed AD and healthy children significantly decreased from 2003 to 2004 (644.2 pg/mL to 448.7 pg/mL and 506.3 pg/mL to 442.1 pg/mL, respectively). The mean TARC level of newly developed AD children significantly increased from 2003 to 2004 (380.1 pg/mL to 491.8 pg/mL). We demonstrated strong associations between TARC levels and the natural course of childhood AD. Monitoring serum TARC levels of AD children may be useful for the biological evaluation of AD.

Detection of autoantibodies to desmoplakin in a patient with oral erythema multiforme.

Anti-desmoplakin (DP) I and II are detected in patients with paraneoplastic pemphigus. However, these autoantibodies have also been detected in patients with other disorders. A 73-year-old woman presented with a 20-year history of erosions and ulcers of the tongue and oral mucosa. Biopsy specimens of the oral mucosa showed several necrotic keratinocytes in the mucosal epithelium. The patient's serum was negative for anti-desmoglein 1 and anti-desmoglein 3 antibodies by ELISA, although anti-keratinocyte cell surface antibodies were detected by indirect immunofluorescence. On immunoblotting using protein extracts of normal human epidermis, the patient's serum was found to contain autoantibodies to 250 kDa and 210 kDa proteins, indicating the presence of autoantibodies to DP I and II. Based on these results, the diagnosis of erythema multiforme was made. An immunofluorescence and immunoblotting are crucial for the differential diagnosis between an erythema multiforme which is positive for anti-DP I and II antibodies and other autoimmune bullous diseases.

Expression of the p38 MAPK, NF-kappaB and cyclin D1 in extramammary Paget's disease.

BACKGROUND: The p38 mitogen-activated protein kinase (MAPK)/nuclear factor kappaB (NF-kappaB)/cyclin D1 signaling pathway has recently been shown to play an important part in the pathogenesis of many human tumors. However, the role of this signal transduction pathway in extramammary Paget's disease (EMPD) remains unknown. OBJECTIVE: This study was designed to investigate the expression of phosphorylated p38 MAP kinasealpha (p-p38 MAPKalpha), phosphorylated NF-kappa B p65 (p-NF-kappaB p65) and cyclin D1 proteins in EMPD and to evaluate the relationship among them. METHODS: Thirty-five tissue samples from 30 primary EMPD cases were analyzed by immunohistochemical staining in formalin-fixed, paraffin-embedded tissue sections for p-p38 MAPKalpha, p-NF-kappaB p65 and cyclin D1. RESULTS: Among the 35 specimens of EMPD, p-p38 MAPKalpha, p-NF-kappaB p65 and cyclin D1 were expressed in 30, 28 and 27, respectively. Moreover, in five metastatic lymph node specimens, all were positive for p-p38 MAPKalpha and p-NF-kappaB p65, four were positive for cyclin D1. There were significant correlations between expression of p-p38 MAPKalpha, p-NF-kappaB p65, and cyclin D1 in EMPD. CONCLUSION: This study provides evidence that p-p38 MAPKalpha, p-NF-kappaB p65, and cyclin D1 was overexpressed in EMPD, suggesting that the p38 MAPK/NF-kappaB/cyclin D1 signaling pathway might participate in the oncogenesis of EMPD.

Incidence of atopic dermatitis in nursery school children - a follow-up study from 2001 to 2004, Kyushu University Ishigaki Atopic Dermatitis Study (KIDS).

Atopic dermatitis (AD) is a multifactorial disease that usually decreases the quality of life of affected patients. We monitored the incidence of AD and serum total IgE levels annually among nursery school children in Ishigaki Island, Okinawa, Japan, from 2001 to 2004. A total of 1731 children were enrolled. The prevalence of AD ranged from 3.7 to 11% in each year, with no significant difference between boys and girls. 869 children were examined at least twice. 71.6% (53/74) of AD patients regressed spontaneously, whereas 5.5% (44/795) of non-AD individuals developed AD during the 3-year follow-up. Increases in total IgE levels were greater and more rapid in children with long-term AD than in those who had spontaneously regressed, had newly-developed AD or did not have AD. The regression rate of AD was > 70% while new-onset AD occurred at a rate of 3.67%/person year in nursery school children of Ishigaki Island.

Anti-CXCR3 staining is useful for detecting human cutaneous and mucosal mast cells.

Human synovial mast cells (MC) can be immunolabelled with antihuman CXCR3 antibody (Ab) (clone 49801). We have investigated whether cutaneous and mucosal MC are stained with anti-CXCR3 Ab in paraffin-embedded sections. Immunohistochemical staining and immunofluorescence double staining assays were performed with anti-CXCR3, anti-tryptase, and anti-chymase Ab using normal skin, psoriatic skin lesions, and normal colon. When compared with tryptase and chymase staining, 100% of the cutaneous and 98% of the mucosal MC were positive for CXCR3. Anti-CXCR3 staining is a useful marker for human cutaneous and mucosal MC in paraffin-embedded sections.