Vogt-Koyanagi-Harada syndrome: a rare but important differential diagnosis of viral meningitis

Vogt-Koyanagi-Harada syndrome (VKHS) is an inflammatory syndrome affecting melanocyte-containing organs. The clinical onset is often acute with neurological and ophthalmological symptoms and there is considerable risk of sequelae if the condition is not promptly diagnosed and treated. We present a case illustrating that VKHS is a rare but important differential diagnosis of viral meningitis.     

Arabidopsis ARF-GTP exchange factor, GNOM, mediates transport required for innate immunity and focal accumulation of syntaxin PEN1

Penetration resistance to powdery mildew fungi, conferred by localized cell wall appositions (papillae), is one of the best-studied processes in plant innate immunity. The syntaxin PENETRATION (PEN)1 is required for timely appearance of papillae, which contain callose and extracellular membrane material, as well as PEN1 itself. Appearance of membrane material in papillae suggests secretion of exosomes. These are potentially derived from multivesicular bodies (MVBs), supported by our observation that ARA6-labeled organelles assemble at the fungal attack site. However, the trafficking components that mediate delivery of extracellular membrane material are unknown. Here, we show that the delivery is independent of PEN1 function. Instead, we find that application of brefeldin (BF)A blocks the papillary accumulation of GFP-PEN1-labeled extracellular membrane and callose, while impeding penetration resistance. We subsequently provide evidence indicating that the responsible BFA-sensitive ADP ribosylation factor-GTP exchange factor (ARF-GEF) is GNOM. Firstly, analysis of the transheterozygote gnom(B4049/emb30-1) (gnom(B)(/E)) mutant revealed a delay in papilla formation and reduced penetration resistance. Furthermore, a BFA-resistant version of GNOM restored the BFA-sensitive papillary accumulation of GFP-PEN1 and callose. Our data, therefore, provide a link between GNOM and disease resistance. We suggest that papilla formation requires rapid reorganization of material from the plasma membrane mediated by GNOM. The papilla material is subsequently presumed to be sorted into MVBs and directed to the site of fungal attack, rendering the epidermal plant cell inaccessible for the invading powdery mildew fungus.     

Neuroendocrine assessment of serotonergic, dopaminergic, and noradrenergic functions in alcohol-dependent individuals

Background: Alcohol dependence has been associated with reduced function of serotonin, dopamine as well as noradrenaline activities in several neuroendocrine studies. To our knowledge, there is, however, no study investigating all these 3 systems with the use of neuroendocrine methods in one and the same alcohol‐dependent individual. Methods: Alcohol‐dependent individuals (n = 42) and controls (n = 28) participated in the neuroendocrine test series. Central serotonergic neurotransmission was assessed by the prolactin (PRL) response to citalopram (CIT). The postsynaptic DRD2 function was measured by the growth hormone (GH) response to apomorphine (APO) and the postsynaptic α2‐adrenoceptor function by GH response to clonidine (CLON). Results: In the alcohol‐dependent individuals, the PRL concentrations were significantly lower at the time points 240 minutes and 300 minutes after CIT administration and mean delta PRL value was significantly reduced by 45% in comparison with controls. There were no significant differences in APO‐GH and CLON‐GH concentrations at any time points or in mean delta GH values between the groups. An impaired monoaminergic profile, including all 3 systems, was significantly more frequent in alcohol‐dependent individuals than controls (43% vs. 6% respectively). Conclusions: The monoaminergic dysfunction was restricted to an impairment of the serotonergic system, suggesting that this system is especially vulnerable to long‐term and excessive alcohol consumption. Moreover, impaired monoaminergic profiles, including low responses in 2 or 3 systems, were more frequently observed in alcohol‐dependent individuals than in controls. Such impaired profiles may be of clinical importance, but further studies are needed.     

Lactobacillus plantarum 299v Does Not Reduce Enteric Bacteria or Bacterial Translocation in Patients Undergoing Colon Resection

Background

Probiotics may exert beneficial effects in the gastrointestinal tract. This randomized trial investigated the effect of the probiotic Lactobacillus plantarum 299v on the intestinal load of potentially pathogenic bacteria, bacterial translocation, and cell proliferation in elective colon surgery.

Methods

Seventy-five patients were randomized to pre- and postoperative oral intake of Lactobacillus plantarum 299v or placebo. Rectal swabs and mucosal biopsies were taken before the start of intake, after 1 week, at surgery, and after 6 days, weeks, and months. Viable counts were quantified for clostridia, Enterobacteriaceae, Gram-negative anaerobes, and lactobacilli. Bacterial translocation was determined by the analysis of bacterial DNA genes in mesenteric lymph nodes. Ki-67 was used as a marker of cell proliferation in normal mucosa and tumor.

Results

Lactobacillus plantarum 299v was given without adverse effects. Lactobacillus plantarum 299v as well as Enterobacteriaceae and Gram-negative anaerobes increased in the colon 1 week after the administration of Lactobacillus plantarum 299v. There were no significant differences between patients receiving Lactobacillus plantarum 299v and placebo in the incidence of bacterial translocation (27 vs. 13 %) and postoperative complications (16 vs. 31 %).

Conclusions

Lactobacillus plantarum 299v was established in the intestine, but no inhibitory effect on enteric bacteria, bacterial translocation, or postoperative complications was found. The mechanism behind the protective effects of probiotics found in animal and some human studies remain elusive and require further explorations. No adverse effects were recorded after the administration of high doses of Lactobacillus plantarum 299v.     

Adult acute lymphoblastic leukaemia in Denmark. A national population‐based retrospective study on acute lymphoblastic leukaemia in Denmark 1998–2008

Since July 2008, children and adults 1–45 years, diagnosed with acute lymphoblastic leukaemia (ALL) in Denmark have been treated according to the common Nordic Society for Paediatric Haematology and Oncology ALL2008 protocol. To explore whether this strategy will improve survival compared with historical controls, we performed a retrospective national population‐based study of adult ALL between 1998 and 2008. Patients were identified through the Danish Patobank and the Danish Cancer Registry; data was collected from patient files, and included 277 patients (median age, 47 years, range 15–91 years). The 5‐year projected event‐free survival (pEFS_5y) and overall survival (pOS_5y) for the whole cohort was 27·5% [95% confidence interval (CI) 22·4–33·6] and 34·1% (95% CI 28·7–40·4), respectively. No patient above 65 years survived beyond 5 years from diagnosis. For patients receiving curatively intended treatment, the pEFS_5y and pOS_5y were 36·6% and 44·1%, respectively, with a significantly higher pOS_5y for patients 15–35 years compared with patients 36–65 years (50·7% vs. 38·9%, P = 0·006). Cox multiple regression analysis identified age (Hazard Ratio = 1·7, P < 0·006) as a statistically significant predictor of EFS. The cure rates, not least for the elderly, are unacceptably low, and call for new strategies in the treatment of adult ALL in all age groups.