Apoptosis of CD4+ T and natural killer cells in Alzheimer's disease

BACKGROUND: Immunotherapy appears to be a potent treatment against Alzheimer's disease (AD), but the mechanisms underlying neural-immune interaction are still not known. METHODS: Here, we determined cell death and distribution of lymphocyte subsets of peripheral blood mononuclear cells (PBMC) in AD and aging, e.g. T (CD4+ CD3+, CD8+ CD3+), B (CD19+) and NK (CD16++CD56+) cells. RESULTS: Increased apoptosis was found in CD4+ T and NK cells in AD, while in aging all subsets were affected. The expression of anti-apoptotic Bcl2 correlated with observed cell death in T-helper and B cells irrespective of dementia. The levels of Bcl2 in T-cells were significantly increased in mild AD. Apoptosis and Bcl2 levels were also elevated in the APP (751SL)xPS1 (M146L) transgenic mouse model. CONCLUSION: The mechanisms triggering apoptosis and activation of lymphocytes in AD appear therefore to be different than those in immunosenescence and possibly bear an important biomarker to monitor immunotherapy in AD.     

Revisiting Traditional Risk Factors for Rejection and Graft Loss After Kidney Transplantation

Single‐antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor‐specific antibody (DSA). We grouped 587 kidney transplants using clinical history and single‐antigen bead (SAB) testing of day of transplant serum as (1) unsensitized; PRA = 0 (n = 178), (2) third‐party sensitized; no DSA (n = 363) or (3) donor sensitized; with DSA (n = 46), and studied rejection rates, death‐censored graft survival (DCGS) and risk factors for rejection. Antibody‐mediated rejection (AMR) rates were increased with DSA (p < 0.0001), but not with panel reactive antibody (PRA) in the absence of DSA. Cell‐mediated rejection (CMR) rates were increased with DSA (p < 0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p = 0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization.     

Total mesorectal excision preserves male genital function compared with conventional rectal cancer surgery.

BACKGROUND: The introduction of total mesorectal excision (TME) has been shown to improve local recurrence rates in rectal cancer. The present study investigated the impact of this more extensive and radical procedure with regard to autonomic pelvic nerve function. METHODS: Patients with resected primary rectal cancer were interviewed by means of a questionnaire asking about preoperative and postoperative urinary bladder and genital function. The results in patients after rectal cancer surgery without TME (group 1; n = 29) were compared with those obtained after introduction of the TME technique (group 2; n = 31). Patients in group 2 were older and had a lower level of anastomosis than patients in group 1. Other patient, treatment and tumour characteristics were comparable between the groups. RESULTS: : Newly acquired and permanent symptoms of bladder dysfunction after rectal excision were present as follows (group 1 versus group 2): difficulty in bladder emptying 7 versus 19 per cent; sensation of incomplete bladder voiding 17 versus 17 per cent; urgency 17 versus 14 per cent; incontinence 10 versus 3 per cent; dysuria 7 versus 7 per cent; and dribbling 14 versus 8 per cent. Male patients stated the following sexual functions before operation/after operation in group 1 versus group 2: interest in sex 80 per cent/40 per cent versus 63 per cent/37 per cent; sexually active 67 per cent/7 per cent versus 53 per cent/22 per cent; impotence 75 per cent/6 per cent versus 58 per cent/26 per cent; ability to have intercourse 75 per cent/13 per cent versus 67 per cent/29 per cent; ability to achieve orgasm 88 per cent/13 per cent versus 76 per cent/47 per cent; and orgasm with ejaculation 88 per cent/9 per cent versus 76 per cent/53 per cent. CONCLUSION: While both conventional rectal cancer surgery and TME result in similarly favourable postoperative bladder function, both techniques decrease sexual function. However, TME offers a significant advantage with regard to preservation of postoperative sexual function in men and constitutes a true advance in rectal cancer surgery compared with conventional techniques.     

Prevalence of Y chromosome microdeletions in infertile men who consulted a tertiary care medical centre: the Münster experience

The long arm of the human Y chromosome is required for male fertility. Microdeletions in three different regions of the human Y chromosome, designated AZFa, AZFb and AZFc, respectively, are frequently associated with male infertility. The varying frequency of Y microdeletions found in cohorts of infertile men (0.4-55.5%) is probably related to the criteria by which the patients are selected. We report the diagnosis of Y chromosomal microdeletion in a total of 1,470 men who attended our infertility clinic, the largest sample of infertile patients to have been analysed to date. This cohort consists of three populations. The first subgroup comprises 228 selected patients with severely impaired spermatogenesis. Since microdeletions had also been reported in patients with less severe defects in spermatogenesis, we then intended to define the deletion frequency in unselected patients (population II: 378 patients). Population III comprises 864 prospectively selected patients and intracytoplasmic sperm injection candidates. Altogether, 19 patients with microdeletions were found (1.3%). The microdeletion frequencies in populations I, II and III were 3.5%, 0.3% and 1.2%, respectively. Our study helps to define a subgroup of infertile men at risk of Y chromosomal microdeletions, and strongly supports the recommendation that Y microdeletion analysis should be limited to azoospermic and severely oligozoospermic men and candidates for intracytoplasmic sperm injection.     

The use of spectral measures of heart rate variability to differentiate between male snorers and patients with sleep apnoea syndrome

Snoring is a characteristic feature of habitual snorers and patients with sleep apnoea syndrome. However, unlike snorers, sleep apnoea patients have an increased peri-operative morbidity. Presently available methods to differentiate between these two groups are either expensive, invasive or time consuming. As cardiac reflexes are impaired in sleep apnoea syndrome, we tested whether heart rate variability could discriminate between snorers and patients with sleep apnoea syndrome. Heart rate variability measurement detects cardiac autonomic dysfunction non-invasively in an ambulatory setting. We studied 32 male patients undergoing polysomnography for suspected sleep apnoea. Total, low- and high-frequency power were measured using a Holter electrocardiogram. Differences in night- and daytime variability were then calculated. Differences between day and night values were more pronounced in the sleep apnoea group and related to the apnoea-hypopnoea-index and low oxygen saturation. Higher values in sleep apnoea patients resulted from increasing variability at night. Heart rate variability might thus help to differentiate between snorers and patients with severe sleep apnoea syndrome.     

One-year results: palatal implants for the treatment of obstructive sleep apnea.

OBJECTIVE: To evaluate long-term effectiveness of palatal implants for treatment of mild to moderate obstructive sleep apnea (OSA). STUDY DESIGN: A prospective study of 26 referred patients with a pretreatment apnea-hypopnea index (AHI) of 10 to 30 and a body mass index of < or =30, representing an extended follow-up of a subset of 41 patients enrolled in previous short-term trials. RESULTS: Twenty-one of 26 patients (80.8%) experienced a decrease in AHI. Fifteen of 26 patients (57.7%) had a follow-up AHI <10 at 1 year, whereas 13 patients (50%) had a 50% or greater reduction to an AHI <10 at 1 year. Mean AHI was reduced from 16.5 +/- 4.5 at baseline to 12.5 +/- 10.5 at 3 months (P < 0.014) and to 12.3 +/- 12.7 at 1 year (P < 0.019). CONCLUSIONS: Patients initially responding to palatal implants with improved AHI maintained improvement through long-term follow-up at 1 year.     

A cross-specialty survey to assess the application of risk stratified surgery for differentiated thyroid cancer in the UK

Introduction

This study describes variability of treatment for differentiated thyroid cancer among thyroid surgeons, in the context of changing patterns of thyroid surgery in the UK.

Methods

Hospital Episodes Statistics on thyroid operations between 1997 and 2012 were obtained for England. A survey comprising six scenarios of varying ‘risk’ was developed. Patient/tumour information was provided, with five risk stratified or non-risk stratified treatment options. The survey was distributed to UK surgical associations. Respondent demographics were categorised and responses analysed by assigned risk stratified preference.

Results

From 1997 to 2012, the Hospital Episode Statistics data indicated there was a 55% increase in the annual number of thyroidectomies with a fivefold increase in otolaryngology procedures and a tripling of cancer operations. Of the surgical association members surveyed, 264 respondents reported a thyroid surgery practice. Management varied across and within the six scenarios, and was not related consistently to the level of risk. Associations were demonstrated between overall risk stratified preference and higher volume practice (>25 thyroidectomies per year) (p=0.011), fewer years of consultant practice (p=0.017) and multidisciplinary team participation (p=0.037). Logistic regression revealed fewer years of consultant practice (odds ratio [OR]: 0.96/year in practice, 95% confidence interval [CI]: 0.922–0.997, p=0.036) and caseload of >25/year (OR 1.92, 95% CI: 1.044–3.522, p=0.036) as independent predictors of risk stratified preference.

Conclusions

There is a substantial contribution to thyroid surgery in the UK by otolaryngology surgeons. Adjusting management according to established case-based risk stratification is not widely applied. Higher caseload was associated with a preference for management tailored to individual risk.     

Lymphokine-induced phagocytosis in angiocentric immunoproliferative lesions (AIL) and malignant lymphoma arising in AIL

A factor that augmented the phagocytosis of IgG-coated ox red blood cells by the human monocyte/macrophage line U937 was identified in cell culture supernatants from two of two patients with angiocentric peripheral T cell lymphomas, three of three patients with angiocentric immunoproliferative lesions that were not frankly malignant, and one of two patients with T lymphoblastic malignancies. The factor was not present in supernatants derived from 14 nonangiocentric peripheral T cell lymphomas of other histologic types nor in ten cases of B cell lymphoma and two cases of Hodgkin's disease. A similar factor was present in the supernatants of concanavalin A (Con A)-stimulated normal peripheral blood mononuclear cells and in the supernatants of IL-2- dependent T cell lines derived from normal peripheral blood. The factor had an apparent mol wt of greater than 50,000 daltons, was heat labile (100 degrees C for two minutes), and stable at pH 2.0. Its stimulation of phagocytosis was independent of any increase in number of Fc receptors. Thus, this factor is probably not gamma-interferon. This factor may play a pathogenetic role in the hemophagocytic syndromes associated with certain T cell malignancies and immunodeficient states.     

Acoustic evoked potentials and topical diagnosis in the central nervous system

Acoustic stimulation evokes about 15 waves, the so-called auditory evoked potentials (AEP). According to their appearance in time there are three groups: early auditory evoked potentials, middle latency AEP and late latency AEP. The shorter the latency of a wave, the more precise the coordination to a definable structure in the CNS. Therefore only EAEP allow besides an evaluation of hearing threshold a differential diagnosis between peripheral, neural and central hearing disturbances. Still unclear are questions such as exact origin of waves II to V and the difference of response due to rarefaction and condensation stimuli. The test, however, is a sensitive indicator to evaluate hearing disturbances and brainstem disorders.