The epidemiology of hyperuricaemia and gout in Taiwan aborigines

To determine the prevalence of hyperuricaemia, gout and gout-related factors in Central Taiwan Atayal aborigines, 342 subjects over 18 yr old were interviewed and examined. A questionnaire was designed to screen for signs and symptoms of gout and gout-related risk factors. Serum uric acid, triglyceride and creatinine were measured in all subjects. The prevalence of hyperuricaemia was 41.4% and that of gout 11.7% in aborigines. The uric acid level was 7.9+/-1.7 mg/dl in males and 5.7+/-1.5 in females, and differed significantly under age 70 yr (P < 0.001). Significantly increased triglyceride, creatinine and alcoholism was found in gouty patients compared with non-gouty patients. In 40 cases with gout, 54% had tophi and 35% of their first- degree relatives had gout. The high prevalence of hyperuricaemia and gout in Taiwan Atayal aborigines, a significant family predisposition, increased creatinine level and alcoholism suggest multiple factors affecting the hyperuricaemia.      

Intestinal pseudo-obstruction as an initial presentation of systemic sclerosis in two children

Two children are reported in whom intestinal pseudo-obstruction was the initial manifestation of systemic sclerosis. Gastrointestinal symptoms and skin changes resolved or improved in both children following treatment with prednisone and penicillamine (case 1) or methotrexate (case 2), although radiological changes of the gastrointestinal tract persisted at 3 and 2 yr of follow-up, respectively.      

Age and bioavailability of alcohol

It has been shown that advanced age results in a decreased first pass metabolism (FPM) of ethanol with elevated serum ethanol concentrations (SECs). It is still unknown if this is due to age by itself or to other factors like for example atrophic gastritis with decreased activity of alcohol dehydrogenase (ADH). To study the effect of age on SECs and on bioavailability of ethanol, 15 volunteers with a mean age of 71 +/- 1 year (8males and 7 females) and 16 volunteers with a mean age of 37 +/- 2 years (8males and 8 females) showing normal gastric histology received ethanol (0.225 g/kg b. w.) intravenously (iv.) and orally.RESULTS: The difference between the SEC time curves after iv. and oral ethanol administration (so called FPM of ethanol) was significantly increased in elderly subjects (54 +/- 6 vs. 12 +/- 9 %, p < 0.001). The SEC time curves after iv. ethanol application were significantly increased in the elderly (p < 0.001), whereas SECs following oral alcohol administration were significantly lower in elderly as compared to younger individuals (p < 0.02). Peak SECs following iv. application was also significantly elevated with age (52 +/- 4 vs. 31 +/- 1 mg/100 ml, p < 0.001) and occurrence of peak SECs following oral ethanol intake was significantly delayed (47 +/- 4 vs. 28 +/- 4 min, p < 0.001). No gender effect at all was observed.CONCLUSION: FPM of ethanol is inexpectedly increased in elderly with normal gastric morphology compared to young people. The elevation of SECs after iv. ethanol administration in the elderly could be explained by the reduction of the water distribution space with age, whereas the increased FPM of ethanol in elderly subjects with normal gastric morphology is probably due to a deceleration of the speed of gastric emptying leading to an increased contact time of alcohol with gastric alcohol dehydrogenase (ADH). Our data do not confirm results from other research groups showing increased SECs in the elderly after alcohol consumption. Increased SECs are therefore not due to age by itself, but are probably caused by other factors as for example atrophic gastritis which is frequently found in the elderly people and which decreases FPM of ethanol.     

Hydroxychloroquine blood levels in stable lupus nephritis under low dose (2–3 mg/kg/day): 12-month prospective randomized controlled trial

Clinical Rheumatology - The American Academy of Ophthalmology (2016-AAO) recommended hydroxychloroquine (HCQ) dose not to exceed 5 mg/kg/day (real body weight). Recently, it was reported that...     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Steatosis recovery after treatment with a balanced sunflower or olive oil-based diet： Involvement of perisinusoidal stellate cells

AIM: To analyze the relationship between perisinusoidal stellate cell (PSC) activation and the dietary fat quantity and composition in the treatment of hepatic steatosis. METHODS: Using an experimental rat model of steatosis based on the intake of a hyperlipidic diet (14% fat as olive oil or sunflower oil, HL-O and HL-S, respectively), we analyzed the liver's capability of recovery after the treatment with a normal-lipidic diet (5% fat as olive oil or sunflower oil, NL-O and NL-S, respectively) by immu-nocytochemical and Western blot analysis of glial fibril-lary acidic protein (GFAP) expression in PSCs, collagen quantification and serum aminotransferase determination. RESULTS: The fatty infiltration in the steatotic livers decreased after the treatment with both NL diets, indicating liver recovery. This decrease was accompanied with a lower collagen deposition and aminotransferase level as well as changes in the PSC population that increased the GFAP expression. The above-mentioned effects were more pronounced in animals fed on NL-O based diet. CONCLUSION: Treatment with a balanced diet enriched in olive oil contributes to the liver recovery from a steatotic process. The PSC phenotype is a marker of this hepatic-recovery model.     

Ultra‐deep T cell receptor sequencing reveals the complexity and intratumour heterogeneity of T cell clones in renal cell carcinomas

The recognition of cancer cells by T cells can impact upon prognosis and be exploited for immunotherapeutic approaches. This recognition depends on the specific interaction between antigens displayed on the surface of cancer cells and the T cell receptor (TCR), which is generated by somatic rearrangements of TCR α‐ and β‐chains (TCRb). Our aim was to assess whether ultra‐deep sequencing of the rearranged TCRb in DNA extracted from unfractionated clear cell renal cell carcinoma (ccRCC) samples can provide insights into the clonality and heterogeneity of intratumoural T cells in ccRCCs, a tumour type that can display extensive genetic intratumour heterogeneity (ITH). For this purpose, DNA was extracted from two to four tumour regions from each of four primary ccRCCs and was analysed by ultra‐deep TCR sequencing. In parallel, tumour infiltration by CD4, CD8 and Foxp3 regulatory T cells was evaluated by immunohistochemistry and correlated with TCR‐sequencing data. A polyclonal T cell repertoire with 367–16 289 (median 2394) unique TCRb sequences was identified per tumour region. The frequencies of the 100 most abundant T cell clones/tumour were poorly correlated between most regions (Pearson correlation coefficient, –0.218 to 0.465). 3–93% of these T cell clones were not detectable across all regions. Thus, the clonal composition of T cell populations can be heterogeneous across different regions of the same ccRCC. T cell ITH was higher in tumours pretreated with an mTOR inhibitor, which could suggest that therapy can influence adaptive tumour immunity. These data show that ultra‐deep TCR‐sequencing technology can be applied directly to DNA extracted from unfractionated tumour samples, allowing novel insights into the clonality of T cell populations in cancers. These were polyclonal and displayed ITH in ccRCC. TCRb sequencing may shed light on mechanisms of cancer immunity and the efficacy of immunotherapy approaches. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Experience with Levosimendan in 32 Paediatric Patients

The aim of this study was to describe the off-label conditions of use for levosimendan in the paediatric population of a tertiary referral hospital. This is a retrospective observational study conducted between January 2007 and January 2014. Inclusion criteria were as follows: 100 % of paediatric patients who received intravenous perfusions of levosimendan during the study period. The following data were gathered: age, sex, diagnosis, dose administered, duration and date of the perfusion, number of perfusions per patient, previous inotropic and concomitant treatment, side effects and survival. A total of 32 patients were included in the study (56 % male). The mean age at the moment of administration was 4 months (range 2 days–15 years). During the study period, a total of 70 infusions were recorded. Fifteen of the 32 patients (46.9 %) received repeat doses, with a mean interval between doses of 8 days (range 3–37 days). The doses used were between 0.05 and 0.2 mcg/kg/min. Loading doses were not used in any cases. At the moment of receiving the infusion, all of the patients were receiving conventional treatment without any response, including inotropic support in 88 % of the cases. The administration of levosimendan was only suspended in one case due to the appearance of severe hypotension. In the rest of the administrations, it was well tolerated, without registering any severe side effect during the infusion process. Levosimendan proved to be a safe, effective strategy in our paediatric population. The good tolerance observed may be related to the absence of an initial bolus or loading dose.