The use of over-the-Counter (OTC) pharmaceuticals is a common phenomenon in today\'s society. We present a case of liver injury associated with long-term OTC use of vitamin A. The young patient took daily up to 15 capsules of a combined preparation for 2 years containing retinol palmitate 55 mg (100,000 IU) + Alpha-Tocopherol acetate 100 mg, the content of vitamin A in which significantly exceeded the recommended daily dose. Gradually, the patient noted the appearance of arthralgia, skin itching, hyperemia of the palms and feet, exfoliation of the skin on the soles, profuse hair loss, cracks in the corners of the mouth and in the area of the earlobes. Patient\'s condition worsened with the development of signs of liver cirrhosis in the form of portal hypertension (ascites, splenomegaly) and a decrease in the protein-synthetic function of the organ. Chronic viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, hemochromatosis, Wilson\'s disease, alcoholic liver disease were exclude. Liver biopsy showed characteristic signs of hypervitaminosis A without fibrosis. A complete regression of symptoms was observe within 8 months after discontinuation of the drug. A toxicity can lead to serious liver injury and should be considere in the differential diagnosis of chronic liver disease. Vitamin A should only be prescribe for medical reasons, for a limited period of time, and under close medical supervision.
Использование безрецептурных средств распространенное явление в современном обществе. Представляем случай поражения печени на фоне длительного безрецептурного приема витамина А. На протяжении 2 лет молодая пациентка ежедневно принимала до 15 капсул комбинированного препарата, содержащего ретинола пальмитат 55 мг (100 тыс. МЕ) + Альфа-Токоферола ацетат 100 мг, содержание витамина А в котором значительно превосходило рекомендуемую суточную дозу. Постепенно пациентка отметила появление артралгий, кожного зуда, гиперемии ладоней и стоп, отслоения кожи на подошвах, обильное выпадение волос, трещины в уголках рта и в области мочек уха. Состояние продолжало ухудшаться с развитием признаков цирроза печени в виде портальной гипертензии (асцит, спленомегалия) и снижения белково-синтетической функции органа. Исключались хронические вирусные гепатиты, аутоиммунный гепатит, первичный билиарный цирроз, гемохроматоз, болезнь Вильсона, алкогольная болезнь печени. При биопсии печени были обнаружены характерные признаки гипервитаминоза А без фиброза. В течение 8 мес после прекращения приема препарата наблюдали полный регресс симптомов. Хроническая токсичность витамина А может приводить к серьезным повреждениям печени и должна учитываться при дифференциальной диагностике хронических заболеваний печени. Назначение витамина А должно осуществляться только по медицинским показаниям, в течение ограниченного периода времени и под тщательным медицинским наблюдением.

Early studies of narcolepsy after AS03-adjuvanted pandemic A/H1N12009 vaccine (Pandemrix) could not define the duration of elevated risk post-vaccination nor the risk in children aged under 5 years who may not present until much older.
Clinical information and sleep test results, extracted from hospital notes at 3 large pediatric sleep centers in England between September 2017 and June 2018 for narcolepsy cases aged 4-19 years with symptom onset since January 2009, were reviewed by an expert panel to confirm the diagnosis. Vaccination histories were independently obtained from general practitioners (GPs). The odds of vaccination in narcolepsy cases compared with the age-matched English population was calculated after adjustment for clinical conditions that were indications for vaccination. GP questionnaires were returned for 242 of the 244 children with confirmed narcolepsy. Of these 5 were under 5 years, 118 were 5-11 years, and 119 were 12-19 years old at diagnosis; 39 were vaccinated with Pandemrix before onset. The odds ratio (OR) for onset at any time after vaccination was 1.94 (95% confidence interval [CI] 1.30-2.89), The elevated risk period was restricted to onsets within 12 months of vaccination (OR 6.65 [3.44-12.85]) and was highest within the first 6 months. After one year, ORs were not significantly different from 1 up to 8 years after vaccination. The ORs were similar in under five-year-olds and older ages. The estimated attributable risk was 1 in 34,500 doses. Our study is limited by including cases from only 3 sleep centers, who may differ from cases diagnosed in nonparticipating centers, and by imprecision in defining the centers\' catchment population. The potential for biased recall of onset shortly after vaccination in cases aware of the association cannot be excluded.
In this study, we found that vaccine-attributable cases have onset of narcolepsy within 12 months of Pandemrix vaccination. The attributable risk is higher than previously estimated in England because of identification of vaccine-attributable cases with late diagnoses. Absence of a compensatory drop in risk 1-8 years after vaccination suggests that Pandemrix does not trigger onsets in those in whom narcolepsy would have occurred later.

We recently presented associations between serum-based biomarkers of carotenoid and tocopherol intake and chronic disease risk in a Women\'s Health Initiative (WHI) Measurement Precision subcohort (n = 5488). Questions remain as to whether self-reported dietary data can usefully augment such biomarkers or can be calibrated using biomarkers for reliable disease association estimation in larger WHI cohorts.
The aims were to examine the potential of FFQ data to explain intake variation in a WHI Feeding Study and to compare association parameter estimates and their precision from studies based on biomarker-calibrated FFQ intake in larger WHI cohorts, with those previously presented.
Serum-based intake measures were augmented by using FFQ data in a WHI Feeding Study (n = 153). Corresponding calibration equations were generated, both in a companion Nutritional Biomarker Study (n = 436) and in the previously mentioned subcohort (n = 5488), by regressing these intake measures on dietary data and participant characteristics, for α- and β-carotene, lutein plus zeaxanthin, and α-tocopherol. The supplemental value of FFQ data was considered by examining the fraction of feeding study intake variation explained by these regression models. Calibrated intake and disease association analyses were evaluated by comparisons with previously reported subcohort results.
The inclusion of FFQ data led to some increases in feeding study intake variation explained (total R2 of ∼50%). Calibrated intake estimates explained 25-75% of serum-based intake variation, whether developed using either of the 2 cohort subsamples. Related disease associations for micronutrients were precisely estimated in larger WHI cohorts (n = 76,691) but were often closer to the null compared with previously reported associations.
FFQ data may usefully augment blood concentrations in estimating the intake of carotenoids and tocopherols. Calibrated intake estimates using FFQ, dietary supplement, and participant characteristics only may require further justification to ensure reliable estimation of related disease associations.

Background: We aimed to determine dietary intake and serum concentration of α-tocopherol and lycopene in subjects with knee osteoarthritis (KOA) in relation to pain intensity and functional status and comparing them with healthy controls. Methods: This case-control study was conducted among 35 patients with primary KOA and 35 matched healthy subjects selected using convenience sampling method. Dietary intakes of alpha-tocopherol and lycopene were estimated from 24-hour dietary records. Visual Analogue Scale (VAS) and Western Ontario and McMaster (WOMAC) index were used to assess the pain and functional status, respectively. Results: Serum concentrations of alpha-tocopherol (0.024 ± 0.005 vs. 0.028 ± 0.007 μmol/ml, p-value =  0.021) and lycopene (0.616 ± 0.191 vs. 0.727 ± 0.159 μmol/l, p-value = 0.011) were significantly lower in OA patients in comparison with healthy controls. Dietary intake of alpha-tocopherol was negatively associated with total WOMAC score (r = -0.401, p-value = 0.021) and pain (r = -0.356, p-value = 0.042) and physical function (r = -0.355, p-value = 0.043) subscales. Dietary intake of lycopene was negatively associated with total WOMAC score (r = -0.616, p-value < 0.001) and pain (r = -0.348, p-value = 0.047) and physical function (r = -0.606, p-value < 0.001) subscales. Additionally, serum concentration of alpha-tocopherol was negatively associated with total WOMAC score (r = -0.574, p-value < 0.001) and physical function subscale (r = -0.571, p-value < 0.001). Serum concentration of lycopene was negatively associated with total WOMAC score (r = -0.360, p-value = 0.040) and physical function subscale (r = -0.350, p-value = 0.046) Conclusion: Serum concentrations of α-tocopherol and lycopene were significantly lower in patients with KOA than in healthy controls. Significant negative association was detected between serum concentration and dietary intake of α-tocopherol and lycopene with functional disability in patients with KOA.

This article summarizes the histories of six patients with different solid tumors treated with a new strategy based on tumor burden reduction and immune evasion as potential targets. All six patients were at a high risk of relapse and were likely to have a minimal residual disease following conventional therapy: biochemical recurrence (BCR) following radical prostatectomy (RP) (two prostate cancers patients), removal of distant metastases (one colorectal and one breast cancer), and complete response (CR) of distant metastases to conventional therapy (one breast cancer and one esophageal-gastric junction cancer). Four of the patients, two after RP and BCR, one after removal of a single pulmonary metastasis from breast cancer, and one after CR to chemotherapy of peritoneal metastases and ascites from an esophageal-gastric junction primary cancer, regularly received cycles of a new drug schedule with the aim of inhibiting immune suppression (IT). In these four patients, preliminary laboratory tests of peripheral blood suggested an interleukin (IL)-2/IL-12 mediated stimulation of cellular immune response with a concomitant decrease in vascular endothelial growth factor (VEGF) immune suppression. The fifth case was a breast cancer patient with distant metastases in CR, while receiving beta-interferon and interleukin-2 in addition to conventional hormone therapy. To date, all five patients are alive and doing well and they have been unexpectedly disease-free for 201 and 78 months following BCR, 28 months following the removal of a single pulmonary metastases, 32 months following CR to chemotherapy of peritoneal metastases and ascites, and 140 months following diagnosis of multiple bone metastases, respectively. The sixth patient, who had colorectal cancer and multiple synchronous liver metastases and underwent nine surgical interventions for metastatic disease, although not disease-free, is doing well 98 months after primary surgery. Our six cases reports can be interpreted with the hypothesis that immune manipulation and/or a concomitant low tumor burden favored their clinical outcome.

To elucidate the roles of vitrification of stabilizers/matrix formers for the redispersibility of drug nanocrystal powder after solidification at storage stress, the influence of different drying methods and storage stresses on stability of drug nanocrystals was systemically investigated. A poorly soluble drug, baicalin, used as model drug was converted into baicalin nanocrystals (BCN-NC). The residual moisture contents of BCN-NC were applied at two different stress conditions defined as \"conservative\" (<1%) and \"aggressive\" (>1%), respectively. The influence of different stabilizers, matrix formers, and storage stresses on the redispersibility of BCN-NC powder was systemically investigated, respectively. The results showed that storage stresses had significantly influence the redispersibility of BCN-NC. Aggressive storage temperature and residual moisture could be unfavorable factors for stability of drug nanocrystals, due to the exacerbation of aggregation of BCN-NC induced by vitrification. It was demonstrated that vitrification of spray-dried BCN-NC was dependent on temperature and time. The polymeric stabilizers hydroxypropylmethylcellulose (HPMC) and sodium carboxymethyl starch (CMS-Na) with high glass transition temperature (T g) played more important role in protecting the BCN-NC from breakage during storage, compared to the surfactants Tween 80, D-α-tocopherol acid polyethylene glycol 1000 succinate (TPGS), or RH 40. Besides, the polyvinylpyrrolidone K30 (PVP K30) and lactose with high T g were effective matrix formers for preserving the redispersibility of BCN-NC. It was concluded that the vitrification transition of stabilizers/matrix formers could be responsible for aggregation of drug nanocrystals during storage, which was a time-dependent process. The suitable residual moisture contents (RMC) and T g were very important for preserving the stability of drug nanocrystals during storage.

Immunoglobulin G4 (IgG4)-related disease is a distinct group of disorders that are characterised by intense infiltration of an organ with IgG4(+) cells, subsequent inflammation, fibrosis, and masses. We report a new treatment of orbital IgG4-related disease with pentoxyphylline and α-tocopherol, both of which are anti-inflammatory and antifibrotic agents.

BACKGROUND: Host antioxidant defense, consisting of enzymatic antioxidant activity and nonenzymatic antioxidant micronutrients, is implicated in asthma pathogenesis. Studies of antioxidant defense and adult incident asthma have either used measures of antioxidants estimated from questionnaires or not considered enzymatic aspects of host defense.
OBJECTIVE: We conducted the first study designed and powered to investigate the association of antioxidant defenses on adult incident asthma.
METHODS: In a nested case-control study, we followed Shanghai women (aged 40-70 years) without prevalent asthma at baseline, over 8 years. Subjects with incident asthma were ascertained prospectively by gold standard testing of symptomatic women and matched to two asymptomatic control subjects.
RESULTS: Baseline urinary F2-isoprostanes, plasma concentrations of antioxidant micronutrients (tocopherols, xanthines, carotenes, and lycopene), and antioxidant enzyme activity (platelet-activating factor acetylhydrolase [PAF-AH] and superoxide dismutase) were measured from samples collected before disease onset. Among 65,372 women, 150 (0.24%) developed asthma. F2-isoprostane levels before asthma onset were not different between cases and control subjects. Doubling of α-tocopherol concentrations and PAF-AH activity was associated with 50 and 37% decreased risk of incident asthma (α-tocopherol: adjusted odds ratio = 0.52; 95% confidence interval, 0.32-0.84; PAF-AH: adjusted odds ratio = 0.63; 95% confidence interval, 0.42-0.93).
CONCLUSIONS: In this prospective study, α-tocopherol, within normal reference ranges, and PAF-AH enzymatic activity were associated with decreased asthma development. These modifiable risk factors may be an effective strategy to test for primary asthma prevention.

BACKGROUND: Noma is a poorly studied disease that leads to severe facial tissue destruction in children in developing countries, but the cause remains unknown. We aimed to identify the epidemiological and microbiological risk factors associated with noma disease.
METHODS: We did a prospective, matched, case-control study in Niger between Aug 1, 2001, and Oct 31, 2006, in children younger than 12 years to assess risk factors for acute noma. All acute noma cases were included and four controls for each case were matched by age and home village. Epidemiological and clinical data were obtained at study inclusion. We undertook matched-paired analyses with conditional logistic regression models.
RESULTS: We included 82 cases and 327 controls. Independent risk factors associated with noma were: severe stunting (odds ratio [OR] 4·87, 95% CI 2·35-10·09) or wasting (2·45, 1·25-4·83); a high number of previous pregnancies in the mother (1·16, 1·04-1·31); the presence of respiratory disease, diarrhoea, or fever in the past 3 months (2·70, 1·35-5·40); and the absence of chickens at home (1·90, 0·93-3·88). After inclusion of microbiological data, a reduced proportion of Fusobacterium (4·63, 1·61-13·35), Capnocytophaga (3·69, 1·48-9·17), Neisseria (3·24, 1·10-9·55), and Spirochaeta in the mouth (7·77, 2·12-28·42), and an increased proportion of Prevotella (2·53, 1·07-5·98), were associated with noma. We identified no specific single bacterial or viral pathogen in cases.
CONCLUSIONS: Noma is associated with indicators of severe poverty and altered oral microbiota. The predominance of specific bacterial commensals is indicative of a modification of the oral microbiota associated with reduced bacterial diversity.
BACKGROUND: Gertrude Hirzel Foundation.

OBJECTIVE: The present study assess the effect of consumption of alcohol on oxidative stress and antioxidant status in patients suffering from different types of cancer.
METHODS: This hospital based case control study conducted in the Western part of Nepal covered a total of 93 cancer patients with or without alcohol intake and smoking habits, along with 94 age, sex and habit-matched individuals serving as controls. Plasma thiobarbituric acid reacting substances (TBARS), total antioxidant activity (TAA), vitamin C, α-tocopherol and erythrocyte reduced glutathione (GSH) were estimated and compared.
RESULTS: The TBARS level was found to be significantly higher (p≤0.001) in all types of cancer patients when compared to controls, being aggravated in alcoholics with a smoking habit. No statistical significance (p≥0.05) was observed in the level of vitamin C and α-tocopherol. GSH and TAA level were significantly decreased (p≤0.001) in all the groups except those who consumed both branded as well as homemade alcohol and non-alcoholics without smoking habit.
CONCLUSIONS: Alcohol, irrespective of its commercial brand, increases oxidative stress in all types of cancer patients. This is even higher when alcohol intake is combined with a smoking habit. Decreased TAA and GSH are major risk factors for cancer development.