Does pre-treatment with micronized progesterone affect the ovarian response to a gonadotropin releasing hormone agonist flare-up protocol?

The purpose of this study was to investigate the ovarian response and the receptivity of the endometrium in women pre-treated with micronized progesterone. Eighty-two normogonodotropic women undergoing in vitro fertilization were studied. Thirty received micronized progesterone 1500 mg/day from day 21 of the cycle for a minimum of 2 weeks, and 52 did not receive micronized progesterone (control group). A gonadotropin releasing hormone agonist (GnRH-a) was administered to all the patients in the follicular phase (flare-up). Twenty-five cycles were cancelled for fertilization failure due to male factor, 12 (40%) in the progesterone group and 13 (25%) in the control group (p = 0.271). There was no difference in the number of oocytes retrieved (7.3 +/- 5 vs. 8.2 +/- 4), fertilization rate (50.8% vs. 65%), clinical pregnancy rate (16.6% vs. 25%) or implantation rate (8% vs. 14%). In the progesterone group cases without fertilization, we performed two biopsies to evaluate the receptivity of the endometrium. Pinopode expression was noted 7 days after oocyte retrieval. It seems that the administration of micronized progesterone in the previous cycle does not affect the ovarian response to the combination of follicular phase GnRH-a and gonadotropins, nor the receptivity of the endometrium.     

Arthroscopic Shoulder Stabilization: Is There Ever a Need to Open?

Recent studies show comparable results of arthroscopic shoulder stabilization techniques compared with the gold standard open Bankart reconstruction. Great technical advances and ever-increasing surgeon experience have rendered pathology once deemed an indication for open surgery as treatable by arthroscopic means. With this movement toward a more universal application of all-arthroscopic techniques, we might consider the following question: Is there ever a need to open? To answer this question, we must first consider normal anatomy and then appreciate the contribution of deranged pathoanatomy to recurrent instability in each individual case. The surgeon must then determine whether this is best addressed via an arthroscopic or open technique. Arthroscopy, as compared with open stabilization procedures, holds the potential benefits of decreased morbidity rates, early functional rehabilitation, and improved range of motion. Despite potential advantages, arthroscopic stabilization is clearly contraindicated when a significant pathologic lesion contributing to recurrent instability cannot be adequately addressed as a result of the limitations of current techniques or instrumentation. On the basis of this principle, we believe that sizable glenohumeral bone defects remain the only absolute contraindication to an all-arthroscopic approach. Many complicating issues, such as attenuated capsule, humeral avulsion of the glenohumeral ligament lesions, cases of revision surgery, and collision or contact athletes, exist and warrant close attention. We prefer to think of these situations as “challenges” for which both arthroscopic and open surgery should be considered, rather than as true contraindications to arthroscopic shoulder stabilization. We are, by no means, advocating arthroscopic treatment in all cases of shoulder instability, because this would represent a gross oversimplification of the issues at hand. However, we do acknowledge that the steadfast contraindications to arthroscopic shoulder stabilization are decreasing every day.     

The human CD40 gene lies within chromosome 20q deletions associated with myeloid malignancies

Deletions of chromosome 20q are associated with myeloid malignancies and have been previously shown to arise in a multipotent progenitor of both myeloid and B cells. However, B-cell differentiation from the abnormal progenitor was impaired. The CD40 antigen is a surface glycoprotein which is expressed in B cells and haemopoietic stem cells and is important for B-cell growth and development. Following the recent mapping of CD40 to chromosome 20q we sought to determine its position relative to 20q deletions. Analysis of lymphoblastoid cell lines carrying 20q deletions placed CD40 within a 19–21 cM interval which is almost coincidental with the common deleted region defined by previous analysis of patient samples. Our results raise the possibility that genetic alteration of this locus may contribute to the pathogenesis of myeloid disorders associated with 20q deletions.     

Thrombophilia in hemodialysis patients: Transfer to peritoneal dialysis is life saving

The majority of vascular access thrombosis episodes in hemodialysis patients are due to anatomic abnormalities. Thrombophilias are inherited, acquired or mixed disorders which also predispose to venous thromboembolism. They include protein C, protein S and antithrombin deficiencies, as well as gene mutations for prothrombin and factor V Leiden. The most important of the mixed cases is hyperhomocysteinemia, which includes both a genetic and an acquired substrate. We report two patients undergoing hemodialysis who suffered from multiple thrombotic events, the first due to factor V Leiden heterozygosity and the second because of hyperhomocysteinemia due to homozygosity for MTHFR C677T mutation. As no site for vascular access was left, transfer to peritoneal dialysis for both patients improved solute clearance and quality of life with no additional thrombotic events noted.     

Clonal haemopoiesis in normal elderly women: implications for the myeloproliferative disorders and myelodysplastic syndromes

Studies of X chromosome inactivation patterns are central to many aspects of our understanding of the pathogenesis of haematological malignancies. In patients with myeloproliferative disorders and myelodysplastic syndromes the demonstration of skewed X inactivation patterns in multiple haemopoietic lineages has been taken to indicate a stem cell origin for these groups of diseases. However, stem cell depletion or selection pressures can also produce skewed X inactivation patterns and might increase with age. We have therefore used the HUMARA assay to study X inactivation patterns of elderly patients with myeloproliferative disorders together with an age-matched control group of normal elderly women.   A clonal pattern (clonal granulocytes and polyclonal T cells) was observed in 23.1% of normal women and 63.4% of patients with myeloproliferative disorders. This is the first report of X inactivation patterns in purified subpopulations of blood cells in normal elderly women. These results have three significant implications. Firstly, the finding of clonal granulocytes and polyclonal T cells in normal elderly women is likely to reflect age-related stem cell depletion or selection pressures. Secondly, the demonstration of clonal granulocytes and polyclonal T cells is not a useful diagnostic marker for myeloproliferative disorders or myelodysplastic syndromes in elderly women. Thirdly, our data raise the possibility that clonal blood cell patterns may precede rather than follow mutations which subsequently give rise to myelodysplastic or myeloproliferative phenotypes.     

Bone structure and geometry in young men: The influence of smoking,alcohol intake and physical activity

BackgroundThe development of osteoporosis is influenced by peak bone mass attained in youth — the influence of lifestyle factors upon which is poorly described, especially amongst males. We sought to address this issue in a large scale study.MethodsHip bone mineral density (dual X-ray absorptiometry, DXA), bone microarchitecture (calcaneal quantitative ultrasound, QUS) and femoral geometry (magnetic resonance imaging, MRI) were characterised in 723 healthy male military recruits (mean ± S.E. age 19.92 ± 0.09 years [range 16–18 years], height 177.67 ± 0.24 cm, weight 73.17 ± 0.37 kg) on entry to UK Army training. Association was sought with prior physical activity, smoking status and alcohol intake.ResultsDXA measures were made in 651, MRI measures in 650, and QUS measures in 572 recruits. Increasing levels of weight-bearing physical activity enhanced periostial bone apposition, increases in both total hip and femoral neck bone mineral density (BMD; p ≤ 0.0001 in both cases), and cortical [p < 0.0001] and periostial bone volumes [p = 0.016]. Smoking habit was associated with preserved bone geometry, but worse BMD [p = 0.0001] and QUS characteristics [p ≤ 0.0005]. Moderate alcohol consumption was associated with greater BMD [p ≤ 0.015].ConclusionsWhilst exercise (and perhaps moderate alcohol intake) is beneficial to bone morphometry, smoking is detrimental to bone mineral density in young males notable for the likely short duration of smoking to influence skeletal properties. However, differences in socio-economic status, lifestyle and related environmental factors may to some extent confound our results.