Increased expression of epidermal growth factor receptor in normal epithelium adjacent to head and neck carcinomas independent of tobacco and alcohol abuse

In this study we examined if expression of the epidermal growth factor receptor (EGFR) in normal epithelium adjacent to head and neck squamous cell carcinomas (HNSCC) is increased and if this increase is due to the use of tobacco and alcohol. MATERIALS AND METHODS: Cut sections of formalin-fixed and paraffin-embedded material of histologically normal epithelium adjacent to HNSCC from 25 patients who smoke excessively and abuse alcohol, and 17 HNSCC patients who do not abuse tobacco and alcohol were compared with cut sections of normal epithelium from 27 control individuals. The sections were immu-nohistochemically stained for the EGFR. RESULTS: We show an elevation of the expression of the EGFR in patients who smoke and drink excessively, that could also be ascertained, to a lesser extent, in patients that do not have a history of smoking or drinking (P = 0.08). We also find that the closer the epithelium lies to the HNSCC the higher the expression of the EGFR is. CONCLUSIONS: Expression of the EGFR is increased in tumour-adjacent epithelium and this is not only due to the use of tobacco and/or alcohol. We suggest that paracrine effects of the HNSCC and migration of tumour cells may also play a role in this increased expression.     

Development of an infection-resistant bifunctionalized Dacron biomaterial

A novel infection-resistant biomaterial was created by applying the antibiotic Ciprofloxacin (Cipro) to a recently developed bifunctionalized polyethylene terephthalate ("polyester," Dacron) material using textile-dyeing technology. Dacron was modified via exposure to ethylenediamine (EDA) to create amine and carboxylic acid sites within the polymer backbone. Cipro was applied to the bifunctionalized Dacron construct under varied experimental conditions, with resulting antimicrobial activity determined via zone of inhibition. Dacron segments treated at a liquor ratio of 20:1, with 5% Cipro on weight of fabric (owf), at pH 8 for 4 h at 70 degrees C followed by autoclaving showed antimicrobial activity for 78 days (length of study). Segments treated similarly but without autoclaving lost activity within 1 day. Dyeing time and temperature did not significantly affect antibiotic release/activity, but segments dyed at pHs higher or lower than 8 had less antimicrobial activity. The long-term infection resistance provided by this technique may answer major problems of infection from which implantable Dacron biomedical devices suffer.     

The meiotic competence of in-vitro matured human oocytes is influenced by donor age: evidence that folliculogenesis is compromised in the reproductively aged ovary

The human oocyte appears to be particularly prone to meiotic errors, and the incidence of these errors is strongly influenced by maternal age. We have initiated studies of human oocytes from unstimulated ovaries and have observed age-related effects on the meiotic process in oocytes from unselected antral follicles. Specifically, in oocytes obtained from donors over the age of 35 years, the majority of oocytes that extruded a first polar body in culture and arrested at second meiotic metaphase had aberrations in spindle formation and chromosome alignment. Similarly, observations of a limited number of oocytes at first meiotic metaphase suggest disturbances at this stage of meiosis as well. Finally, preliminary results of non-disjunction studies suggest that the frequency of errors in chromosome segregation at the first meiotic division is influenced by donor age in in-vitro matured oocytes as it is in oocytes undergoing meiotic maturation in vivo. These data provide direct evidence that the meiotic competence of oocytes from unstimulated ovaries declines with donor age. Similarly, studies of in-vitro fertilization (IVF) pregnancies in older women indicate that the developmental competence of the human oocyte declines with age. Since both meiotic and developmental competence are acquired during the late stages of oocyte growth, we postulate that an age- related decline in the process of folliculogenesis results in reduced oocyte quality and that the well characterized age-related increase in meiotic non-disjunction is one symptom of compromised oocyte growth.      

Torque teno virus load as marker of rejection and infection in solid organ transplantation – A systematic review and meta-analysis

Balancing immunosuppression to prevent rejection in solid organ transplant (SOT) recipients remains challenging. Torque teno virus (TTV), a commensal non-pathogenic virus, has been proposed as marker of functional immunity: higher loads correspond to over-immunosuppression, and lower loads to under-immunosuppression. This review offers an overview of the current evidence of the association between TTV-load and infection and rejection after SOT. A systematic literature search strategy, deposited in the PROSPERO registry, resulted in 548 records. After screening, 23 original and peer-reviewed articles were assessed investigating the association between TTV-load, infection and/or rejection in SOT. The Quality in Prognostic Studies (QUIPS)-tool was used to assess the risk of bias. Meta-analysis with random-effects was performed on results with similar outcomes and exposure measures. Most of the included studies involved retrospective cohorts in which the TTV-load was measured longitudinally, within the first 2 years post-transplantation. Infection outcomes differed between studies and included viral, bacterial, parasitic and fungal infections. Rejection was defined by biopsy confirmation or initiation of rejection treatment. Twelve out of 16 studies reported an association between high TTV-load and infections, whereas 13 out of 15 reported an association between low TTV-load and rejection. Meta-analysis showed an increased risk of infection (OR: 1.16, 95% CI: 1.03–1.32; HR: 1.05, 95% CI: 0.97–1.14) and a decreased risk of rejection (OR: 0.90, 95% CI: 0.87–0.94; HR: 0.74, 95% CI: 0.71–0.76) per 1 log TTV-load increase. The qualitative assessment showed varying risks of bias in the included studies. This systematic review and meta-analysis indicates that blood TTV-load measured within the first 2 years after SOT is associated with the risk of infection or allograft rejection, although substantial risk of bias in the studies included warrant cautious interpretation. The results in this review provide a rationale for larger, prospective, studies into TTV as marker of infection and rejection after SOT.     

Impaired B cell maturation in mice lacking Bruton's tyrosine kinase (Btk) and CD40

Mutations in Bruton's tyrosine kinase (Btk) gene, in mice, result in reduced numbers and responses of peripheral B cells. Surface Ig- mediated signaling is defective in Btk mutant B cells as they do not proliferate upon slg cross-linking and lack thymus-independent (TI) type II responses. Signals through sIg and CD40 play a critical role in B cell maturation. To investigate the consequences of the lack of both Btk and CD40 on B cell development and function, mice were generated that were homozygous for targeted mutations in the Btk and the CD40 genes (BtkMCD40M). The CD40 mutation (CD40M) had a synergistic effect on the BtkM defects. In BtkMCD40M mice the number of B cells was reduced 3- to 4-fold compared to BtkM mice and mature B cells (IgMlow/IgDhigh) were virtually absent; serum levels of all Ig isotypes were diminished; and antibody responses to TI-I TI-II and thymus- dependent antigens were impaired. Furthermore, although wild-type BtkM and CD40M mice produced germinal centers in response to TI-I antigen, the BtkMCD40M mice did not. Maturational and functional B cell defects in BtkMCD40M mice may result from a combination of intrinsic B cell defects, lack of CD40L-dependent T cell help and microenvironmental defects. These data suggest that signals through Btk and CD40 are necessary for the production and maintenance of the mature B cell.      

Health care use and costs associated with use of a health club membership benefit in older adults with diabetes

OBJECTIVE—The purpose of this study was to determine whether elective use of a health plan–sponsored health club membership had an impact on health care use and costs among older adults with diabetes.RESEARCH DESIGN AND METHODS—Administrative claims for 2,031 older adults with diabetes enrolled in a Medicare Advantage plan were obtained for this retrospective cohort study. Participants (n = 618) in the plan-sponsored health club benefit (Silver Sneakers [SS]) and control subjects (n = 1,413) matched on SS enrollment index date were enrolled in the plan for at least 1 year before the index date. Two-year health care use and costs of SS participants and control subjects were estimated in regressions adjusting for baseline differences.RESULTS—SS participants were more likely to be male, had a lower chronic disease burden, used more preventive services, and had a lower prevalence of arthritis (P ≤ 05). SS participants had lower adjusted total health care costs than control subjects in the first year after enrollment (−$1,633 [95% CI −$2,620 to −$646], P = 0.001), and adjusted total costs in year 2 trended lower (−$1,230 [−$2,494 to $33], P = 0.06). Participants who made on average ≥2 SS visits/week in year 1 had lower total costs in year 2 ($2,141 [−$3,877 to −$405], P = 0.02) than participants who made <2 visits/week.CONCLUSIONS—Use of a health club benefit by older adults with diabetes was associated with slower growth in total health care costs over 2 years; greater use of the benefit was actually associated with declines in total costs.Health care costs associated with diabetes account for 32% of total Medicare spending (1). Clinical practice guidelines recommend physical activity as an important component of diabetes management (2) and for prevention of cardiovascular complications (3), but only 16% of individuals aged 65–74 years engage in at least 30 min of moderate activity ≥5 days/week (4). The benefits of physical activity for older adults include better health, improved functioning, increased quality of life, lower health care costs, and longer survival (5–8). There is growing recognition that environmental conditions and policies that promote physical activity can have an impact on modifiable behavioral risks and chronic conditions (9,10).Health plan promotion and direct support of physical activity via sponsored exercise programs have the potential to reach many people because 61% of younger Americans had employment-based health insurance in 2004 (11) and nearly 100% of older Americans have Medicare coverage. Two previous studies of a health plan–sponsored community-based group exercise program (EnhanceFitness) for Medicare Advantage plan enrollees showed that participants in a general population (12) and in a subgroup of members with diabetes (13) who made greater use of the exercise program had lower adjusted health care costs than less active participants and control subjects. A third study examined the cost impact of a health club membership (Silver Sneakers [SS]) sponsored by the same Medicare Advantage plan with older adult members and found that SS use was associated with slower growth in total health care costs, particularly for the most active SS participants (14).This study extends prior studies by examining whether the health care use and cost impacts of SS participation found in older adults also apply to the subset of older adults with diabetes who have the most to gain from regular physical activity. We compared dose effects of SS participation on health care use and costs, based on a dose threshold of <2 or ≥2 visits/week. This study may provide further evidence of whether health plan–sponsored health club memberships provide a return on investment for older adults with chronic conditions and the level of participation needed to reduce health care costs.     

Sequential introduction of single room isolation and hand hygiene campaign in the control of methicillin-resistant <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> in intensive care unit

Background  

After renovation of the adult intensive care unit (ICU) with installation of ten single rooms, an enhanced infection control program was conducted to control the spread of methicillin-resistant Staphylococcus aureus (MRSA) in our hospital.