Circulating Survivin Levels in Obstructive Sleep Apnoea

Introduction

Obstructive sleep apnoea (OSA) is characterised by a low-grade systemic and airway inflammation; however, the regulatory mechanisms of inflammation are poorly explored. Survivin (Birc5) is an anti-apoptotic protein which inhibits Type 1 inflammation; however, this molecule has not been investigated in OSA.

Methods

Forty-five patients with OSA and 31 non-OSA control subjects were involved. Venous blood was collected for plasma survivin measurements before and after diagnostic overnight polysomnography. Plasma survivin levels were compared between the two groups and correlated to OSA severity and comorbidities.

Results

Plasma survivin levels were lower in OSA in the evening (27.6?±?89.9 vs. 108.3?±?161.2 pg/ml, p?<?0.01) and in the morning (17.4?±?48.6 vs. 36.4?±?69.2 pg/ml, p?=?0.02) compared to the control group. This OSA-related decrease was also present when only the non-obese patients were analysed. Significant indirect relationships were observed between plasma survivin levels and measures of OSA severity such as the apnoea–hypopnoea index (r?=???0.45) or oxygen desaturation index (r?=???0.40, both p?<?0.01); however, when adjusting to BMI, these became insignificant (p?>?0.05). Low plasma survivin concentrations were associated with high BMI (r?=???0.35), high CRP (r?=???0.31), low HDL cholesterol (r?=?0.24) and high triglyceride levels (r?=???0.24, all p?<?0.05).

Conclusion

Plasma survivin levels are reduced in OSA, relate to disease severity, and are associated with high CRP levels. This suggests an impaired immunoregulation in this disorder which needs to be studied in further detail.

     

Biologics in oral medicine: ulcerative disorders

Oral Diseases (2012) 19 , 37–45 Inflammatory ulcerative diseases of the oral mucosa are wide ranging but include especially aphthous and aphthous‐like ulceration, vesiculobullous disorders and erosive lichen planus (LP). While most patients with these conditions respond to conventional topical and/or systemic immunosuppressive agents, treatment‐resistant cases remain challenging. In these, the use of biologics such as tumour necrosis factor alpha (TNF‐α) inhibitors or rituximab may be of benefit. This article reviews the use of biologics in ulcerative oral conditions, highlighting potential benefits, adverse effects and principles of use and future developments. TNF‐α inhibitors such as infliximab can be effective in inducing resolution in oral aphthous and aphthous‐like ulcers and may be an appropriate therapy in those patients in which disease is severe and refractory to, or patients are intolerant of, traditional immunomodulatory regimens. There would also seem support and rationale for use of biologics (mainly rituximab) in pemphigus but not in oral LP or other oral ulcerative conditions.     

Correlation of testicular sperm extraction with morphological, biophysical and endocrine profiles in men with azoospermia due to primary gonadal failure

To identify the predictive factors for testicular sperm extraction (TESE) and to understand the pathology associated with TESE, we carried out a prospective study in 40 consecutive men with azoospermia due to primary gonadal failure. The main outcome measure was the retrieval of at least one testicular spermatozoon. Endocrine and biophysical profiles, testicular histology, Johnsen score and testicular spermatids were used as predictors of sperm extraction. Spermatogenesis was quantified with the Johnsen score. A variable pattern of spermatogenesis was common, being present in 20 (50%) patients. Visualisation of testicular spermatids on testicular histology showed a strong association with TESE (P < 0.0001). Statistically significant differences were detected in plasma follicle stimulating hormone (FSH) and testicular volume between patients who had hypospermatogenesis and Sertoli cell-only or maturation arrest. There were no significant differences in Johnsen score, biophysical and endocrine profiles between the groups with successful and failed TESE. However, a statistically significant trend occurred with changes in histological pattern [chi2 for trend, P = 0.001; Pearson's coefficient (r) = 0.6], Johnsen score (P = 0.022; r = 0.5), testicular volume (P = 0.01; r = 0.5) and plasma FSH concentrations (P = 0.044; r = 0.4), albeit to a limited degree. Difference in the interpretation of histological patterns with different assessors was observed. The type of occupation or risk factors for azoospermia showed no association with testicular pathology or TESE. Variable histological patterns in different tubules in the same individual may explain the poor correlation of TESE with endocrine and biophysical profiles, Johnsen score and histological pattern. Differences in the amount of tissue used for TESE and histopathology, and misinterpretation of testicular histology rather than failure to quantify spermatogenesis may explain the poor correlation between histological patterns and TESE. Testicular spermatids predicted TESE. However, considerable overlap in values means that no single variable can provide a perfect discrimination between the groups with successful and failed TESE.      

Retrograde tubal embryo transfer in natural cycle in-vitro fertilization

Two modes of embryo transfer, uterine and tubal, were compared following natural cycle in-vitro fertilization (IVF). Only patients with patent Fallopian tubes were included in the study. Tubal embryo transfer was performed by retrograde tubal cannulation without analgesia on an outpatient basis. Tubal transfer conferred no benefit compared with uterine transfer in male factor infertility with positive fertilization (pregnancy rates of 15.8% in both groups). Although tubal embryo transfer in the patients with unexplained infertility improved the pregnancy rates from 7.8% in uterine transfer (5/64) to 17.6% in the tubal transfer group (13/74), this improvement was not statistically significant.      

Cytokines and immuno-endocrine factors in recurrent miscarriage

Recurrent miscarriage remains an enigma. The main aetiologiesare endocrinological, immunological and unexplained. With thegrowth in molecular biology, it is now possible to look at theeffect of these aetiologies in more detail, allowing greaterunderstanding of the underlying pathogenesis. Keywords: cytokines/recurrent miscarriage     

Longitudinal morphological change of acetabular subchondral bone cyst after total hip arthroplasty in developmental dysplasia of the hip

Purpose

The purpose of this study is to clarify morphological changes of acetabular subchondral bone cyst after total hip arthroplasty for osteoarthritis secondary to developmental dysplasia of the hip.

Methods

Two hundred and sixty-one primary cementless total hip arthroplasties of 208 patients, 18 males, 190 females, were retrospectively reviewed. Morphological changes of subchondral bone cyst were evaluated by computed tomography (CT). The mean cross-sectional area of the cyst from CT scans at 3 months postoperatively and after 7–10 years (average 8.4 years) were compared.

Results

Acetabular subchondral bone cysts were found in 49.0% of all cases in preoperative CT scans. There was no cyst which was newly recognized in CT scan performed after postoperative 7–10 years. All the cross-sectional areas of the cysts evaluated in this study were reduced postoperatively.

Conclusions

This study revealed that acetabular subchondral bone cysts do not increase or expand after total hip arthroplasty and indicated that the longitudinal morphological change of acetabular bone cysts in patients of developmental dysplasia of the hip do not influence long-term implant fixation in total hip arthroplasty.

     

The human homologue of rat NG2, a chondroitin sulfate proteoglycan, is not expressed on the cell surface of normal hematopoietic cells but is expressed by acute myeloid leukemia blasts from poor-prognosis patients with abnormalities of chromosome band 11q23

In our efforts to produce monoclonal antibodies that recognize cell- surface antigens expressed by hematopoietic precursor and stromal cells, we generated a monoclonal antibody, 7.1, which recognizes a 220- to 240-kD cell-surface protein whose N-terminal amino acid sequence is identical to the rat NG2 chondroitin sulfate proteoglycan molecule. This chondroitin sulfate proteoglycan, previously reported to be expressed by human melanoma cells, was not found to be expressed by normal hematopoietic cells, nor was it expressed on the cell surface of cell lines of hematopoietic origin including cell lines with 11q23 abnormalities. It was found on the cell surface of acute myeloid leukemia (AML) blasts and cell lines derived from nonhematopoietic tissues. Samples of leukemic marrow from 166 children with AML enrolled on Childrens Cancer Group protocol 213 were evaluated for cell-surface expression of this proteoglycan molecule. In 18 of 166 (11%) patient samples, greater than 25% of leukemic blasts expressed the NG2 molecule. These 18 patients had a poorer outcome with respect to survival (P = .002) and event-free survival (P = .035) with an actuarial survival at 4 years of 16.7%. Blast cell expression of the NG2 molecule was strongly associated with French-American-British M5 morphology (P < .0001) and abnormalities in chromosome band 11q23, site of the MLL gene. These results show that the NG2 molecule is expressed by malignant hematopoietic cells that have abnormalities in chromosome band 11q23, suggesting that antibody 7.1 may be useful in the rapid identification of this group of poor-prognosis patients.