Hepatotoxicity in HIV-infected children and adolescents on antiretroviral therapy.

CONTEXT AND OBJECTIVE: Adverse drug reactions are a significant problem in patients on antiretroviral therapy (ART). We determined liver enzyme elevation frequencies in HIV-infected children and adolescents receiving ART, and their association with risk factors. DESIGN AND SETTING: Cross-sectional study, at the Pediatrics Immunodeficiency Division, University Hospital, Universidade Estadual de Campinas. METHODS: Medical records of 152 children and adolescents (54.6% male; median age 7.48 years) were analyzed, with a mean of 2.6 liver enzyme determinations per patient. Clinically, patients were classified in categories N (6), A (29), B (78) and C (39). Serum levels of aspartate aminotransferase and alanine aminotransferase were evaluated. Hepatotoxicity was scored as grade 1 (1.1-4.9 times upper limit of normality, ULN), grade 2 (5.0-9.9 times ULN), grade 3 (10.0-15.0 times ULN) and grade 4 (> 15.0 times ULN). To assess hepatotoxicity risk factors, odds ratios (OR) and adjusted odds ratios (aOR) for age, gender, TCD4+ cell count, viral load and medication usage were calculated. RESULTS: We observed grade 1 hepatotoxicity in 19.7 % (30/152) patients. No cases of grade 2, 3 or 4 were detected. There was a significant association between hepatotoxicity and use of sulfonamides (OR, 3.61; 95% confidence interval (CI), 1.50-8.70; aOR, 3.58; 95% CI, 1.44-8.85) and antituberculous agents (OR, 9.23; 95% CI, 1.60-53.08; aOR, 9.05; 95% CI, 1.48-55.25). No toxicity was associated with ART. CONCLUSIONS: One fifth of patients experienced mild hepatotoxicity, attributed to antituberculous agents and sulfonamides. Our results suggest that ART was well tolerated.     

An evaluation of web-based informations about gastroesophageal reflux diseases in Korea]

BACKGROUND/AIMS: Internet has become an important source of medical information not only for medical personnels but also for patients. The aim of this study was to evaluate the quality of internet based medical information about 'gastroesophageal reflux' or 'reflux esophagitis' in Korea. METHODS: The first 15 internet sites using the key words 'gastroesophageal reflux' or 'reflux esophagitis' were retrieved from the 7 most frequently used internet search engines. The quality of information from a total of 108 websites was evaluated using a checklist. RESULTS: Among total 108 sites related to 'gastroesophageal reflux' or 'reflux esophagitis', fifty-six sites (51.8%) were made by hospitals or clinics and 94 sites (87.0%) were made for patients. Of the 108 sites, eleven web sites (10.1%) had more than three JAMA benchmarks (authorship, references, currency, and disclosure). Higher quality sites (at least three JAMA benchmarks) were less likely to contain inaccurate information than lower quality sites (fewer than three JAMA benchmarks)-3/11 (27.2%) vs. 60/97 (61.9%) (p<0.01). Despite the fact that articles in the literature emphasized an insufficient evidence to support an association between the lifestyle, dietary behaviors, and GERD, such guidelines continue to be recommended as first-line therapy in most websites. CONCLUSIONS: Informations about gastroesophageal reflux disease were incomplete in the majority of medical web sites. These would bring about confusion to patients seeking for an information about GERD through the internet. There is a need for better sources in evidence based informations about gastroesophageal reflux diseases on the web.     

The short-term effects of high-dose testosterone on sleep,breathing, and function in older men

Androgen therapy may precipitate obstructive sleep apnea in men. Despite increasing androgen use in older men, few studies have examined sleep and breathing. Randomized, double-blind, placebo-controlled studies examining effects of testosterone simultaneously on sleep, breathing, and function in older men are not available. Seventeen community-dwelling healthy men over the age of 60 yr were randomized to receive three injections of im testosterone esters at weekly intervals (500 mg, 250 mg, and 250 mg) or matching oil-based placebo and then crossed over to the other treatment after 8 wk of washout. Polysomnography, anthropometry, and physical, mental, and metabolic function were assessed at baseline and after each treatment period. Testosterone treatment reduced total time slept ( approximately 1 h), increased the duration of hypoxemia ( approximately 5 min/night), and disrupted breathing during sleep (total and non-rapid eye movement respiratory disturbance indices both increased by approximately seven events per hour) (all P < 0.05). Despite expected effects on body composition (increase in total and lean mass, reduction in fat mass, P < 0.05, bioimpedance method), upper airway dimensions did not change (acoustic reflectometry). Driving ability (computer simulation), physical activity (accelerometry, Physical Activity Scale in the Elderly), quality of life (SF36, Functional Outcomes of Sleep Questionnaire), mood (Profile of Mood States Questionnaire), sleepiness (Epworth, Stanford scales), and insulin resistance (homeostasis model) also were not changed by treatment. Short-term administration of high-dose testosterone shortens sleep and worsens sleep apnea in older men but did not alter physical, mental, or metabolic function. These changes did not appear to be due to upper airway narrowing. Further study of longer-term lower-dose androgen therapy on sleep and breathing is needed to evaluate its safety in older men.     

Tissue transglutaminase autoantibodies in children with newly diagnosed type 1 diabetes are related to human leukocyte antigen but not to islet autoantibodies: A Swedish nationwide prospective population-based cohort study

Abstract

Objectives: This study explored the association between tissue transglutaminase autoantibody (tTGA), high-risk human leucocyte antigen (HLA) genotypes and islet autoantibodies in children with newly diagnosed type 1 diabetes (T1D).

Patients and methods: Dried blood spots and serum samples were taken at diagnosis from children <18?years of age participating in Better Diabetes Diagnosis (BDD), a Swedish nationwide prospective cohort study of children newly diagnosed with T1D. We analyzed tTGA, high-risk HLA DQ2 and DQ8 (DQX is neither DQ2 nor DQ8) and islet auto-antibodies (GADA, IA-2A, IAA, and three variants of Zinc transporter; ZnT8W, ZnT8R, and ZnT8QA).

Results: Out of 2705 children diagnosed with T1D, 85 (3.1%) had positive tTGA and 63 (2.3%) had borderline values. The prevalence of tTGA was higher in children with the HLA genotypes DQ2/2, DQ2/X or DQ2/8 compared to those with DQ8/8 or DQ8/X (p?=?.00001) and those with DQX/X (p?≤?.00001). No significant differences were found in relation to islet autoantibodies or age at diagnosis, but the presence of tTGA was more common in girls than in boys (p?=?.018).

Conclusion: tTGA at T1D diagnosis (both positive and borderline values 5.4%) was higher in girls and in children homozygous for DQ2/2, followed by children heterozygous for DQ2. Only children with DQ2 and/or DQ8 had tTGA. HLA typing at the diagnosis of T1D can help to identify those without risk for CD.     

Decidualization of intranodal endometriosis in a postmenopausal woman

Here we describe an unusual case of decidualized endometriosis detected in pelvic lymph nodes. The presence of intranodal ectopic decidua in pregnant women has been described. A few cases of decidualization of endometriotic foci in the pelvic or para-aortic lymph nodes have also been associated with pregnancy. However, decidualized intranodal endometriosis occurring in a postmenopausal woman has not been described. A 52-year-old woman presented with a very large adnexal mass. Menopause occurred at the age of 47, and she had been treated with hormone replacement therapy. She received a total abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic and para-aortic lymphadenectomy for clear cell carcinoma of the right ovary. Histological examination revealed the presence of ectopic decidua in several pelvic lymph nodes. The deciduas consisted of sheets of loosely cohesive, large, uniform, round cells with abundant eosinophilic cytoplasm. Typical of decidualization of intranodal endometriosis, a few irregularly shaped, inactive endometrial glands lined by single layers of columnar to cuboidal epithelium were present within the decidua. An immunohistochemical study revealed that the decidual cells were positive for CD10, vimentin, estrogen receptor and progesterone receptor, which indicated that progestin-induced decidualization had occurred in the intranodal endometriotic stroma. To the best of our knowledge, this case represents the first report of decidualized intranodal endometriosis occurring in association with hormone replacement therapy in a postmenopausal woman. Misdiagnosis of this condition as a metastatic tumor can be avoided by an awareness of these benign inclusions, supported by immunohistochemical staining results.     

Analysis of clinical outcomes of patients with adenoid cystic carcinoma of Bartholin glands

Adenoid cystic carcinoma of Bartholin glands (BG-ACC) is a rare, slow-growing but a highly aggressive tumor with remarkable capacity for local recurrence and distant metastasis. The purpose of this study was to elucidate our experiences of the diagnosis and treatment of BG-ACC and to analyze the clinical outcomes and prognosis of patients with BG-ACC. A retrospective chart review was performed to assess the demographic information, chief complaints, pathologic features of tumors, primary treatment, and development of local recurrence or distant metastasis, as well as the patient outcome. All patients received surgical excision as the primary treatment, and the diagnosis of BG-ACC was confirmed histopathologically. Three of four patients whose tumors showed pathologic features indicating a high probability of recurrence received adjuvant radiotherapy. These patients did not develop local recurrence, in contrast, one patient who did not receive adjuvant radiotherapy developed local recurrence and distant metastasis on several occasions. All patients who received primary surgical treatment are alive to date. When patients who are more than 40 years of age and who present with symptomatic BG lesions, BG-ACC should be included in the differential diagnosis and biopsy should be performed for histopathologic confirmation. Radical local excision with sufficient negative margins seems to be beneficial for primary treatment. Adjuvant radiotherapy is a reasonable treatment option for patients with high risk factors after surgery or for patients who develop local recurrence.     

Primary ovarian carcinoid tumor showing unusual histology and nuclear accumulation of β-catenin

Carcinoid tumor of the ovary is uncommon. We herein report a very rare case of primary ovarian carcinoid tumor with aggressive histology and an unusual immunophenotype. A 21-year-old woman presented with a palpable abdominal mass. Computed tomographic scan revealed a large, extensively necrotic solid mass in the left ovary. The patient underwent a left salpingo-oophorectomy. Grossly, the left adnexa showed a large, vaguely lobulated ovarian tumor measuring 22×15×13 cm. Histologically, the tumor had a readily identifiable neuroendocrine growth pattern, but some areas showed solid growth pattern associated with mild nuclear pleomorphism and multiple foci of punctate necrosis. Furthermore, mitotic figures were recognized in 8 per 10 high-power fields, and a few foci of large coagulative tumor necrosis were also noted. In addition, the tumor tissue exhibited uniform, strong nuclear β-catenin immunoreactivity, indicating the nuclear accumulation of β-catenin in the individual tumor cells. In summary, we described the first case of primary ovarian carcinoid tumor with loss of neuroendocrine growth pattern, increased mitotic activity and large areas of coagulative tumor necrosis. According to the WHO classification of pulmonary carcinoid tumor, this case may be classified as “atypical” carcinoid. However, currently, no primary ovarian atypical carcinoid exists in the classification system. Due to its rarity, there are no established diagnostic criteria and clinical data on patient outcomes for ovarian carcinoid tumors with aggressive histology. Additional reports are clearly necessary. We also showed for the first time the nuclear accumulation of β-catenin in carcinoid tumor cells, suggestive of a role for β-catenin in the tumorigenesis of ovarian atypical carcinoid tumor or its aggressive histology.