Association of sleep‐disordered breathing with decreased cognitive function among patients with dementia

Sleep is known to be essential for proper cognitive functioning. Sleep disturbance, especially respiratory disturbance during sleep, is a risk factor for the development of dementia. However, it is not known whether hypopnoea during sleep is related to severity of cognitive function in patients already diagnosed with dementia. Considering the high prevalence of sleep problems in aged people, it is important to determine if hypopnoea during sleep contributes to dementia. In addition, it would be desirable to develop a feasible method for objectively evaluating sleep in patients with dementia. For this purpose, a simple sleep recorder that employs single or dual bioparameter recording, which is defined as a type‐4 portable monitor, is suitable. In this study, a type‐4 sleep recorder was used to evaluate respiratory function during sleep in 111 patients with dementia, and data suggesting a possible relationship with cognitive function levels were examined. Multivariate logistic regression was used to investigate the association of severity of dementia with sleep‐disordered breathing, age, diabetes, dyslipidaemia and hypertension. It was found that the respiratory disturbance index was associated with severity of cognitive dysfunction in our subjects. Furthermore, patients younger than 80 years were more susceptible to lower cognitive function associated with sleep‐disordered breathing than patients 80 years old or over, because an increase in the respiratory disturbance index was associated with deteriorated cognitive function only in the former age group. These results suggest that proper treatment of sleep apnea is important for the preservation of cognitive function, especially in patients with early‐stage dementia.     

Impact of CYP2C19 polymorphism on clinical outcome following coronary stenting is more important in non-diabetic than diabetic patients

Objective

The aim of this study was to examine the impact of CYP2C19 genotype on clinical outcome in coronary artery disease (CAD) patients with or without diabetes mellitus (DM).

Methods

CYP2C19 polymorphism and DM are associated with increased risk of cardiovascular events during antiplatelet therapy following stent implantation. Platelet reactivity during clopidogrel therapy and CYP2C19 polymorphism were measured in 519 CAD patients (males 70%, age 69 years) treated with stent placement. Patients were divided into two groups; DM (n = 249), and non-DM (n = 270), and clinical events were evaluated according to the carrier state, which included at least one CYP2C19 loss-of-function allele.

Results

The level of platelet reactivity and incidence of cardiovascular events were significantly different between Carriers and non-Carriers of the non-DM (platelet reactivity: 4501 +/− 1668 versus 3691 +/− 1714AUmin, P < 0.01; events, 32/178 versus 2/92, P < 0.01, respectively), however, there was no difference in clinical outcome in the DM group (events, 34/168 versus 14/81, respectively, P = 0.57). Multivariate analysis identified CYP2C19 loss-of-function allele carriage as an independent predictor of cardiovascular events in non-DM, but not in DM (non-DM, HR 7.180, 95% CI, 1.701 to 30.298, P = 0.007; DM, HR 1.374, 95% CI, 0.394 to 4.792, P = 0.618).

Conclusion

The impact of CYP2C19 polymorphism on clinical outcome seems to be more significant in non-DM compared with DM in patients with coronary stents.     

Chronic kidney disease status modifies the association of CYP2C19 polymorphism in predicting clinical outcomes following coronary stent implantation

Introduction

There is some controversy regarding the effect of CYP2C19 polymorphism on clinical outcome in patients with dual antiplatelet therapy. Chronic kidney disease (CKD) is associated with increased risk of cardiovascular event, but the association between the possession of CYP2C19 loss-of-function (LOF) alleles and clinical outcome according to the presence of CKD is poorly understood. The aim of this study was to investigate whether CKD status modifies the association of CYP2C19 polymorphism in predicting outcomes in a prospective cohort study.

Material and Methods

We enrolled 331 patients following coronary stent implantation. Patients were divided into two groups: CKD (n = 154) and non-CKD (n = 177). Platelet reactivity and CYP2C19 polymorphism were examined. The subjects were further divided into two groups according to the possession of CYP2C19 LOF alleles: carriers and non-carriers. Patients were followed up and clinical events were evaluated according to CKD and carrier status.

Results

The proportion of high platelet reactivity was significantly higher in carriers than in non-carriers in both CKD (42.4% versus 21.7%; P = 0.016) and non-CKD groups (34.3% versus 3.7%; P < 0.001). In the non-CKD group alone, the incidence of cardiovascular events was significantly higher in carriers than in non-carriers (13.7% versus 1.7%; P = 0.013). Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in carriers than in non-carriers in the non-CKD group (log-rank test: P = 0.013) and there was no significant difference in the CKD group (log-rank test: P = 0.591). Multivariate analysis identified carriers as an independent predictor of cardiovascular events only in the non-CKD group alone (hazard ratio: 8.048; 95% confidence interval: 1.066 to 60.757; P = 0.043).

Conclusions

CYP2C19 polymorphism significantly correlates with clinical outcome in non-CKD patients, and CKD status modifies the association of CYP2C19 polymorphism in predicting clinical outcomes following coronary stent implantation.     

Tumor initiating but differentiated luminal-like breast cancer cells are highly invasive in the absence of basal-like activity

The majority of human breast cancers exhibit luminal epithelial differentiation. However, most aggressive behavior, including invasion and purported cancer stem cell activity, are considered characteristics of basal-like cells. We asked the following questions: Must luminal-like breast cancer cells become basal-like to initiate tumors or to invade? Could luminally differentiated cells within a basally initiated hierarchy also be tumorigenic? To answer these questions, we used rare and mutually exclusive lineage markers to isolate subsets of luminal-like and basal-like cells from human breast tumors. We enriched for populations with or without prominent basal-like traits from individual tumors or single cell cloning from cell lines and recovered cells with a luminal-like phenotype. Tumor cells with basal-like traits mimicked phenotypic and functional behavior associated with stem cells assessed by gene expression, mammosphere formation and lineage markers. Luminal-like cells without basal-like traits, surprisingly, were fully capable of initiating invasive tumors in NOD SCID gamma (NSG) mice. In fact, these phenotypically pure luminal-like cells generated larger and more invasive tumors than their basal-like counterparts. The tumorigenicity and invasive potential of the luminal-like cancer cells relied strongly on the expression of the gene GCNT1, which encodes a key glycosyltransferase controlling O-glycan branching. These findings demonstrate that basal-like cells, as defined currently, are not a requirement for breast tumor aggressiveness, and that within a single tumor there are multiple “stem-like” cells with tumorigenic potential casting some doubt on the hypothesis of hierarchical or differentiative loss of tumorigenicity.     

Fulminant candidemia diagnosed by prompt detection of pseudohyphae in a peripheral blood smear

A 77-year-old man treated with prednisolone for pemphigus developed severe sepsis by Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus. Several antibiotics were administered. A peripheral blood smear showed growth of a large number of yeast extending pseudohyphae which could be seen both inside and outside of leucocytes. Antifungal agents were added immediately; however, he did not recover. Several days later, blood culture showed Candida albicans septicemia. The autopsy revealed microabscesses in the lung, heart, liver and kidney. A large amount of neutrophil invasion and yeast with pseudohyphae were also detected.     

Class II high angle case for which titanium screws were added after mandibular posterior rotation

In skeletal Class II patients with a high mandibular plane angle, it is well known that posterior rotation of the mandible often occurs during treatment using a preadjusted edgewise appliance. In this case, posterior rotation of the mandible with increased overjet occurred after the buccal inclination of the mandibular 2nd molars. This case report describes a Class II high angle case for which titanium screws were added as an absolute anchorage to improve the posterior rotation of the mandible. To correct the posterior rotation of the mandible, mandibular molars were intruded and the mandibular arch was mesially moved using titanium screws. The treatment results show that titanium screws were useful for improving the posterior rotation of the mandible during treatment using a preadjusted edgewise appliance.     

CD48 as a novel molecular target for antibody therapy in multiple myeloma

Monoclonal antibody (mAb) drugs are desirable for the improvement of multiple myeloma (MM) treatment. In this study, we found for the first time that CD48 was highly expressed on MM plasma cells. In 22 out of 24 MM patients, CD48 was expressed on more than 90% of MM plasma cells at significantly higher levels than it was on normal lymphocytes and monocytes. CD48 was only weakly expressed on some CD34(+) haematopoietic stem/progenitor cells, and not expressed on erythrocytes or platelets. We next examined whether CD48 could serve as a target antigen for mAb therapy against MM. A newly generated in-house anti-CD48 mAb induced mild antibody-dependent cell-mediated cytotoxicity and marked complement-dependent cytotoxicity against not only MM cell lines but also primary MM plasma cells in vitro. Administration of the anti-CD48 mAb significantly inhibited tumour growth in severe combined immunodeficient mice inoculated subcutaneously with MM cells. Furthermore, anti-CD48 mAb treatment inhibited growth of MM cells transplanted directly into murine bone marrow. Finally and importantly, we demonstrated that the anti-CD48 mAb did not damage normal CD34(+) haematopoietic stem/progenitor cells. These results suggest that the anti-CD48 mAb has the potential to become an effective therapeutic mAb against MM.