Impact of Lanthanum Carbonate on Cortical Bone in Dialysis Patients with Adynamic Bone Disease

Among the most serious problems in patients with chronic kidney disease ( CKD ) is fragility of cortical bone caused by cortical thinning and increased cortical porosity; the cortical fragility is sometimes irreversible, with fractures generally initiating from cortical bone. Therefore, development of treatments for problems of cortical bone is urgently desired. Cortical bone has the three surfaces, including the periosteal surface, intracortical spaces and endocortical surface. Bone turnover at the endocortical surface and intracortical resorption spaces are increased as compared with that at cancellous surface. Bone growth sometimes depends on apposition at the periosteal surface. We treated hyperphosphatemia in two hemodialysis patients with adynamic bone disease with 750–1500 mg/day of lanthanum carbonate, which is a non‐calcium containing phosphate binder; the treatment resulted in a decrease of the serum phosphorus levels ( P levels), without significant change of the serum intact parathyroid hormone levels. We now report that treatment of these patients with lanthanum carbonate increased mineralization of the periosteal surface, increased bone mass within the intracortical resorption spaces and increased mineralization of the minimodeling surface at the endocortical surface. In addition, woven bone volume in cortical bone was decreased and mineralization of bone units, namely, osteons, was increased. Although these findings were not observed across all surfaces of the cortical bone in the patients, it is expected that lanthanum carbonate would increase the cortical stability in CKD patients, with consequent reduction in the fracture rate in these patients.

Sodium oxybate to treat alcohol dependence: 20 years of clinical experience

Detection of IgG and IgE reactivity to BP180 using the ISAC ® microarray system

Summary Background  Bullous pemphigoid (BP) is an autoimmune skin disease in which patient autoantibodies react with BP180 and BP230 proteins. In addition to IgG, IgE has been shown to play a role in the disease. Objectives  To evaluate the feasibility of detecting IgE and IgG against the immunodominant BP180 NC16A domain (BP180) using a microarray system. Methods  BP180 was immobilized on an experimental version of the ISAC ® microarray (Exp96). The BP study group and the controls were all tested on the commercial ISAC 103 version and on the Exp96. IgG and IgE were measured in a single run. BP180 IgG and IgE results were compared with those using an enzyme‐linked immunosorbent assay (ELISA). Results  All results obtained using the IgG ELISA on the 31 patients with BP were replicated with the ISAC IgG. Five of eight BP sera tested by ELISA showed similar results with ISAC IgE. Twenty‐nine (94%) and 19 (61%) of the 31 patients with BP were IgG and IgE positive to BP180, respectively, whereas four (3%) and six (4%) of 138 normal donors were IgG and IgE positive, respectively. Interestingly, the levels of IgG against BP180 detected using the ISAC system were related to the disease severity. Patients with BP showed a peculiar profile of IgE recognition toward some groups of allergens, which was absent in a group of allergic individuals. A significant, higher prevalence of hen’s egg recognition was observed in patients with BP who had specific IgE to BP180. Conclusions  The present preliminary study indicates that the ISAC microarray system is suitable for detecting IgG and IgE autoantibodies in patients with BP. Notably, this system allows the assessment of IgE and IgG autoantibodies at the same time, could be employed for the detection of autoantibodies to other autoantigens, and allows profiling for specific IgE to allergens.

Peamaclein – A new peach allergenic protein: similarities, differences and misleading features compared to Pru p 3

Summary Background Among the peach‐derived allergens which are already known, the lipid transfer protein (Pru p 3) seems to be the one to exert severe allergic reactions. Objective To identify and characterize a new peach allergen causing a clinical picture similar to that of Pru p 3. Methods Patients were selected on the basis of their severe clinical reactivity and negative results to a panel of peach allergens available on the ISAC 103 microarray. Several in‐house and commercial preparations were compared. Several methods were used to characterize the newly identified molecule. Specific IgE and inhibition assays were performed using the Allergen micro‐Beads Array ( ABA ) assay. Results Negative ISAC results to Pru p 3 were confirmed by additional testing in contrast with the positive results obtained by commercial Pru p 3‐enriched peach peel extracts. The analyses of one of these preparations led to the identification of Peamaclein, a new allergenic protein. It is a small, basic, cysteine‐rich, heat‐stable, digestion‐resistant protein, homologous to a potato antimicrobial peptide. Peamaclein was able to trigger positive skin test reactions and to bind IgE in the ABA assay. It displays an electrophoretic mobility and chromatographic behaviour similar to that of Pru p 3; therefore, it can be hidden in Pru p 3 preparations. In fact, Pru p 3‐enriched peach peel extracts were found to contain both Pru p 3 and Peamaclein by means of comparative in vivo testing, and by biochemical and immunochemical assays. Commercially available anti‐Pru p 3 polyclonal antibodies were found to have a double specificity for the two molecules. Conclusions and Clinical Relevance A new allergen from peach belonging to a new family of allergenic proteins has been identified and characterized. This knowledge on Peamaclein will improve our understanding on the clinical aspects of the peach allergy and the quality of diagnostic reagents.

Aggravation of A lzheimer's disease symptoms after the earthquake in J apan: A comparative analysis of subcategories

We recently reported that patients with Alzheimer’s disease (AD) experienced a significant worsening of symptoms after the earthquake and tsunami that occurred in Japan on 11 March 2011. Our previous analysis showed that patients with AD who experienced the disaster had deteriorated with regard to both cognitive functions, and behavioral and psychological symptoms of dementia (BPSD) compared with those

Plasma trough levels of adalimumab and infliximab in terms of clinical efficacy during the treatment of psoriasis

We examined the relation between adalimumab and infliximab plasma trough levels, anti‐adalimumab and anti‐infliximab antibody formation. We analyzed plasma from 32 adalimumab‐treated and 20 infliximab‐treated psoriasis patients for evaluating trough levels of each drug. The presence of anti‐adalimumab and anti‐infliximab antibodies was analyzed and the severity of psoriasis was evaluated. At week 28, 25 out of 32 and at week 48, 21 out of 30 adalimumab‐treated patients maintained as more than PASI 75. At week 28, 12 out of 20 and at week 48, nine out of 18 infliximab‐treated patients were evaluated as more than PASI 75. In patients treated with 40 mg adalimumab every other week, the mean trough level was 7.62 μg/mL (range, 0.05–10.6) at week 48. In patients treated with 80 mg adalimumab every other week, the mean trough level was 8.61 μg/mL (range, 0.08–13.5) at week 48. Mean trough level of infliximab‐treated cases (4.1–5.2 mg/kg; mean, 4.6) was 4.64 μg/mL (range, 0.03–16.9) at week 48. Anti‐adalimumab antibody was detected in five out of 32 cases and anti‐infliximab antibody was detected in six out of 20 cases, respectively, at weeks 24 and 48. The optimal cut‐off values of adalimumab and infliximab concentration for more than PASI 75 were more than 7.84 μg/mL and more than 0.92 μg/mL, respectively. The trough levels of adalimumab and infliximab in psoriasis patients were positively associated with clinical response and were significantly lower in cases having anti‐adalimumab or anti‐infliximab antibodies.

Peptidoglycan‐induced T helper 2 immune response in mice involves interleukin‐10 secretion from Langerhans cells

Patients with atopic dermatitis (AD) have superficial skin colonization with Staphylococcus aureus and an increased number of T helper (Th)2 cells in their peripheral blood. The purpose of this study was to clarify the involvement of interleukin (IL)‐10 secretion from Langerhans cells (LCs) in staphylococcal peptidoglycan (PEG)‐induced Th2 immune responses in mice. Mice were primed with LCs pulsed with PEG (or LPS) and ovalbumin (OVA) and then given a booster OVA injection 2 days later in the hind footpad. Five days after the OVA injection, cytokine responses in the draining popliteal lymph nodes were investigated by RT‐PCR and ELISA. Production of both IL‐10 and IL‐12 by cultured LCs was detected by ELISA. Administration of PEG‐ or LPS‐stimulated LCs into the hind footpads of the mice induced Th2‐prone and Th1‐prone immune responses, respectively, as represented by expression of IL‐4 and interferon ‐γ . In vitro experiments showed that PEG induced greater production of IL‐12 p40 from LCs than did LPS, whereas LPS induced greater production of IL‐12 p70 from LCs than did PEG. Furthermore, it was found that PEG‐stimulated LCs induced greater production of IL‐10 than did LPS‐stimulated LCs, and that neutralization of IL‐10 augmented IL‐12 p70 production and inhibited Th2 development by PEG‐stimulated LCs. These results suggest that PEG can induce Th2 development through down‐regulation of IL‐12 p70 production by LCs in an IL‐10 production‐dependent manner and would explain the role of S. aureus colonization in patients with AD.

Nurse managers’ preferred and perceived leadership styles: a study at an Italian hospital

Aim  The aim of this cross‐sectional descriptive study was to compare the different leadership styles based on perceptions of nurse managers and their staff. Background  Nurse managers’ styles are fundamental to improving subordinates’ performance and achieving goals at health‐care institutions. Methods  This was a cross‐sectional study. A questionnaire developed by Ekvall & Arvonen, considering three leadership domains (Change, Production and Employee relations), was administered to all nurse managers and to their subordinates at a city hospital in north‐east Italy. Results  The comparison between the leadership styles actually adopted and those preferred by the nurse managers showed that the preferred style always scored higher than the style adopted, the difference reaching statistical significance for Change and Production. The leadership styles preferred by subordinates always scored higher than the styles their nurse managers actually adopted; in the subordinates’ opinion, the differences being statistically significant in all three leadership domains. Implication for nursing management  The study showed that nurse managers’ expectations in relation to their leadership differ from those of their subordinates. These findings should be borne in mind when selecting and training nurse managers and other personnel, and they should influence the hospital’s strategic management of nurses.

A novel stop codon mutation within the hepatitis B surface gene is detected in the liver but not in the peripheral blood mononuclear cells of HIV‐infected individuals with occult HBV infection

Summary.  To characterize occult HBV infection (OHB) in different compartments of HIV+ individuals. This retrospective study involved 38 consecutive HIV+ patients; 24 HBsAg negative (HBV−) and 14 HBsAg positive (HBV+). OHB was assessed in serum samples, liver tissue (LT) and peripheral blood mononuclear cells (PBMC) by genomic amplification of the partial S, X and precore/core regions. HBV genomic analysis was inferred by direct sequencing of PCR products. The intracellular HBV‐DNA was measured by a quantitative real‐time PCR. HBV+ patients were used as a control for HBV replication and genomic profile. In HBV− patients, HBV‐DNA was undetectable in all serum samples, while it was found positive in 7/24 (29%) LT in which genotype D prevailed (57%). HBV‐DNA was found in 6/7 (86%) PBMC of occult‐positive and none of occult‐negative LT. Significantly lower HBV‐DNA load was present in both compartments in OHB+ with respect to the HBV+ group (LT: P  = 0.002; PBMC: P  = 0.026). In the occult‐positive cases, HBV replication was significantly higher in LT than in PBMC ( P  = 0.028). A hyper‐mutated S gene in PBMC and a nucleotide mutation at position C695 in LT that produces a translational stop codon at amino acid 181 of the HBs gene characterized OHB. In this group of HIV+ persons, OHB is frequent and exhibits lower replication levels than chronic HBV in the different compartments examined. HBV‐DNA detection in PBMC may offer a useful tool to identify OHB in serum‐negative cases. The novel HBs gene stop codon found in LT could be responsible for reduced production leading to undetectability of HBsAg.

Postoperative recurrence of Crohn’s disease: impact of endoscopic monitoring and treatment step‐up

Aim  Eighty per cent of patients with Crohn’s disease require surgery, of whom 70% will require a further operation. Recurrence occurs at the anastomosis. Although often recommended, the impact of postoperative colonoscopy and treatment adjustment is unknown. Method  Patients with a bowel resection over a 10‐year period were reviewed and comparison made between those who did and did not have a postoperative colonoscopy within 1 year of surgery, and those who did or did not have a step‐up in drug therapy. Results  Of 222 patients operated on, 136 (65 men, mean age 33 years, mean disease duration 8 years, median follow‐up 4 years) were studied. Of 70 patients with and 66 without postoperative colonoscopy, clinical recurrence occurred in 49% and 48% (NS) and further surgery in 9% and 5% (NS). Eighty‐nine per cent of colonoscoped patients had a decision based on the colonoscopic findings: of these, 24% had a step‐up of drug therapy [antibiotics ( n  = 10), aminosalicylates ( n  = 2), thiopurine ( n  = 5), methotrexate ( n  = 1)] and 76% had no step‐up in drug therapy. In colonoscoped patients clinical recurrence occurred in 9 (60%) of 15 patients with, and 23 (49%) of 47 without step‐up and surgical recurrence in 2 (13%) of 15 and 4 (9%) of 47 (NS). Conclusion  Clinical recurrence occurs in a majority of patients soon after surgery. In this cohort, there was no clinical benefit from colonoscopy or increased drug therapy within 1 year after operation. However, the response to the endoscopic findings was not standardized and immunosuppressive therapy was uncommon. Standardizing timing of colonoscopy and drug therapy, including more intense therapy, may improve outcome, although this remains to be proven.