Flow Cytometric Evaluation of Traditional and Novel Surface Markers for the Diagnosis of Plasma Cell Dyscrasias.

Increasing interest has been expressed for flow cytometric immunophenotyping for diagnosis and monitoring in plasma cell dyscrasias over the last decades. The aim of this investigation was to compare the expression strength of various cell surface markers used traditionally or currently under investigation on normal and abnormal PC populations. We enrolled 295 consecutive patients undergoing bone marrow aspiration in the workup of monoclonal gammopathies, selecting 54 normal and 241 abnormal PC populations via flow cytometry to characterize the expression of CD45, CD38, CD138, CD19, CD56, CD20, CD27, CD28, CD81, CD117 and CD200 on the cell surface of PCs. We observed significant differences in the expression strength of all assessed markers between normal and abnormal PC populations in all markers except for CD20. While none of them was conclusive on its own, the combination of CD81 positivity and CD117 negativity was present in 98.1% of normal PC populations tested. In contrast, particularly CD117 positivity, but also CD81 negativity was indicative of an abnormal PC phenotype. Our results highlight the descriptive value of CD81 and CD117 for the allocation of bone marrow PCs to a normal or abnormal phenotype.

Using the Wharton-Sheares-George method to create a neovagina in patients with Mayer-Rokitansky-Küster-Hauser syndrome: a step-by-step video tutorial.

OBJECTIVE: To provide a review of the literature regarding this technique as well as a step-by-step description with the goal of increasing its use as a safe surgical option. Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is characterized by vaginal agenesis and a variety of mullerian duct anomalies. To date, a variety of procedures have been described for creating a neovagina, but the best treatment remains debated. The Wharton-Sheares-George method, a minimally invasive surgical approach for the creation of a neovagina, is remarkably simple to perform. DESIGN: Surgical video tutorial. SETTING: University hospital and referral center for pediatric and adolescent gynecology. PATIENT(S): A 20-year-old woman with MRKH syndrome who underwent Wharton-Sheares-George neovaginoplasty. INTERVENTION(S): With the Wharton-Sheares-George neovaginoplasty the rudimentary müllerian ducts are dilated incrementally by pushing Hegar dilators in the direction of the pelvic axis, and the resulting median raphe is then intersected using diathermy. Subsequently a vaginal mold is inserted into the newly created cavity and held in position by two sutures. MAIN OUTCOME MEASURE(S): Discussion of the surgical steps according to the Wharton-Sheares-George method and review of the anatomic and functional results. RESULTS: Reviewing the existing literature shows that a mean vaginal length and width of 8.3 and 3.3 cm, respectively, can be achieved, and so far no major intraoperative or postoperative complications or prolapse of the neovagina has been reported. Patients can achieve a high degree of general well-being as well as sexual and psychosocial functioning. However, as with most other methods, the presented method requires diligent patient compliance due to the lifelong need to actively avoid contraction of the neovagina. Also, as revealed by vaginal cultures and biopsies, the neovaginas remarkably resemble natural vaginas with regard to type of bacterial colonization and structure of epithelium. The process of spontaneous epithelialization of the neovagina is not fully understood, but has been observed to begin at the vaginal orifice and take several months to reach the apex. This leads to the assumption that the nonkeratinizing, stratified squamous epithelium originates from the preexisting vaginal epithelium of the vaginal dimple and migrates in a cranial direction. Alternatively, epithelialization might arise from pluripotent stem cells located in the obliterated müllerian ducts. CONCLUSION(S): The creation of a neovagina using the Wharton-Sheares-George method does not require allogenic or autologous transplants, nor does it require traction devices or specialized surgical equipment. Furthermore, the procedure is comparatively simple to perform and easy to learn. By following our step-by-step description of this technique, surgeons can offer a minimally invasive, quick, and safe surgical option that provides long-term results that are both functionally and anatomically satisfying. We believe that this technique represents a valuable alternative for the creation of a neovagina in patients with MRKH syndrome and thus should be investigated on a broader scale in the future.

Subclinical hypothyroidism and mortality in a large Austrian cohort: a possible impact on treatment?

BACKGROUND: Clinical implications of subclinical hypothyroidism (SCH) are still matter of intense debate, resulting in the controversial discussion whether subclinical hypothyroidism should be treated. We performed a cohort study to evaluate the impact of subclinical hypothyroidism on vascular and overall mortality. METHODS: Between 02/1993 and 03/2004, a total of 103,135 persons attending the General Hospital Vienna with baseline serum thyrotropin (TSH, thyroid-stimulating hormone) and free thyroxin (fT4) measurements could be enrolled in a retrospective cohort study. Subclinical hypothyroidism was defined by elevated TSH ranging from 4.5 to 20.0 mIU/L and normal fT4 concentration (0.7-1.7 ng/dL). Overall and vascular mortality as primary endpoints were assessed via record linkage with the Austrian Death Registry. RESULTS: A total of 80,490 subjects fulfilled inclusion criteria of whom 3934 participants (3.7%) were classified as SCH (868 males and 3066 females, median age 48 years). The mean follow-up among the 80,490 subjects was 4.1 years yielding an observation period of 373,301 person-years at risk. In a multivariate Cox regression model adjusted for age and gender TSH levels showed a dose-dependent association with all-cause mortality. The association between SCH and overall or vascular mortality was stronger in men below 60 years compared to older males or females. CONCLUSION: Our data support the hypothesis that SCH might represent an independent risk factor for overall and vascular mortality, especially in men below 60 years. Whether this group would benefit from replacement therapy should be evaluated in interventional studies.

Mean platelet volume may represent a predictive parameter for overall vascular mortality and ischemic heart disease.

OBJECTIVE: An increased mean platelet volume (MPV), as an indicator of larger, more reactive platelets resulting from an increased platelet turnover, may represent a risk factor for overall vascular mortality, including myocardial infarction. We intended to identify patients at higher risk of dying from vascular disease in a large, hospital-based cohort. METHODS AND RESULTS: A total of 206 554 first-ever admissions to the Allgemeines Krankenhaus Wien for determination of MPV between January 1996 and July 2003 were included. Primary end points were overall vascular mortality and death due to ischemic heart disease. Multivariate Cox regression adjusted for sex, age, and platelet count was applied for analysis. MPV values were categorized into quintiles, with the lowest quintile serving as the reference category. Compared with individuals with lower MPV (<8.7 fL), hazard ratios for overall vascular mortality gradually increased to 1.5 in the highest category (≥11.01 fL). The relationship of MPV to ischemic heart disease was even stronger and increased from 1.2 (8.71 to 9.60 fL category) to 1.8 in the highest category (≥11.01 fL). CONCLUSIONS: Our results indicate that patients with an increased MPV (≥11.01 fL) are at higher risk of death due to ischemic heart disease, with hazard ratios comparable to those reported for obesity or smoking.