Primary prevention of ischemic stroke: A statement for healthcare professionals from the Stroke Council of the American Heart Association.
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Biomedical subjects
Publications and source records attributed to M Hill.
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This paper documents the resilience of medical and nursing profession-based subcultures and the extent of the differences between them. Against this background, we assess the capacity and willingness of medical and nursing managers to promote changes that will extend the accountability of clinicians and engender more evidence-based, financially driven and output-oriented approaches to service delivery.
Statistical software often offers a list of various descriptive statistics of location and scale, but rarely selects an efficient estimate that is statistically adequate for an actual univariate sample. The sample interval estimate for a specified degree of uncertainty seems to be more meaningful if it covers an unknown value of the population parameter. The concept of an interval estimate in medicine is then used for medical decision-making. The proposed methodology, which uses the S-Plus algorithm for biochemical, biological and clinical data analysis contains the following steps: (i) Exploratory data analysis identifies basic statistical features and patterns of the data, the distributions of which are mostly non-normal, non-homogeneous and often corrupted by outliers. (ii) Sample assumptions about data, independence of sample elements, normality and homogeneity are examined. (iii) Power transformation and the Box-Cox transformation to improve sample symmetry and stabilize the spread. (iv) Classical and robust statistics for both large (n>30) and medium-sized samples (15<n<30), point and interval estimates for the parameters of location, scale and shape. For an analysis of small samples (4<n<20) the Horn procedure of pivot measures is recommended. The proposed methodology is demonstrated in two case studies, a large sample analysis of mean pregnenolone concentrations in the umbilical blood of newborns, and a small sample analysis of mean haptoglobin concentrations in human serum.
The occurrence of acne in women with hyperandrogenemia is well known; a question remains, however, as to whether a further positive relationship can be detected between the intensity of acne and the levels of testosterone, androgen precursors and sex hormone binding globulin (SHBG). A procedure of interactive data analysis extracting relevant information from original data was applied. Exploratory data analysis (EDA) identifies basic statistical features and patterns of data using a variety of diagnostic displays. The need for this step is particularly acute in biochemical and clinical data, the distribution of which is mostly non-Gaussian and often corrupted by the outliers. The omission of EDA can lead to incorrect results and false conclusions. In the EDA (i) several graphical tools for summarizing data are applied, (ii) the peculiarities of a sample distribution are investigated, (iii) a construction of distribution is carried out, (iv) a graphical comparison of the sample distribution with selected theoretical distributions is employed. The proposed procedure is illustrated by typical case study in the evaluation of differences between mean values of serum levels of testosterone, androgen precursors and SHBG in a group of patients with mild and severe forms of acne. A knowledge of the interval estimate of the mean value in both groups enables their comparison at the chosen probability level. As will be apparent from the evaluation of inter-group SHBG differences, an incorrect approach to the determination of group mean values could result in a complete misinterpretation of the data. The results indicate that androgens are not significantly related to the intensity of acne, and that SHBG is higher in patients with more severe forms of acne.
Autoimmune thyroiditis with hypothyroidism is frequently accompanied by symptoms of psychiatric disorders and atherogenic changes in lipid metabolism. Recent studies suggest that some neuroactive steroids and homocysteine are involved in the pathophysiology of both disorders. Homocysteine metabolism may be affected by some steroids. We were interested if the treatment of hypothyroidism would affect the above factors. We studied plasma concentrations of allopregnanolone, pregnenolone sulfate, dehydroepiandosterone and its sulfate, progesterone, estradiol and homocysteine in 14 patients (12 women, 2 men) during the 3-month treatment with levothyroxine. Steroids and thyroid function were monitored by measuring thyrotropin, free triiodothyronine, free thyroxine and levels of thyroid antimicrosomal antibodies and antibodies to thyroglobulin. We have found that with the restoration of the thyrotropin level, free triiodothyronine, free thyroxine and homocysteine levels decreased, but the levels of steroids were not significantly altered. Steroid concentrations correlated negatively with the level of thyroid antimicrosomal antibodies.
OBJECTIVE: To evaluate adrenal and ovarian steroidogenesis before and after long-term treatment with metformin in women with polycystic ovary syndrome (PCOS). DESIGN AND METHODS: Twenty-four women with PCOS were evaluated before and after treatment (27+/-4 weeks) with metformin (1000 mg/day) using adrenocorticotrophin (ACTH), GnRH analogue and oral glucose tolerance (oGTT) tests. For statistical evaluation, ANOVA and Wilcoxon's test were used. RESULTS: In 58% of the women a significant improvement in menstrual cyclicity was observed. No significant change in basal steroid levels was found. After ACTH stimulation, a significant decrease in the activity of 3 beta-hydroxysteroid dehydrogenase in C(21) steroids (P<0.05) and in 17 beta-hydroxysteroid dehydrogenase (P<0.01) was observed, as was an increase in the activity of C17,20-lyase in the Delta(4) pathway (P<0.01). A significant growth in the dehydroepiandrosterone (DHEA)/DHEA-sulfate ratio (P<0.05) was detected. With regard to ovarian steroidogenesis, a significant decrease in the stimulated levels of testosterone (P<0.05), index of free testosterone (P<0.01), LH (P<0.05) and oestradiol (P<0.01), and an increase in the levels of 17-hydroxypregnenolone (P<0.05) were detected. In the indices of ovarian enzyme activities, we observed a significant decrease in 3 beta-hydroxysteroid dehydrogenase in C21 steroids (P<0.01), in C17,20-lyase in the Delta 5 pathway (P<0.01), in 17 beta-hydroxysteroid dehydrogenase (P<0.05) and in aromatase. In glucose metabolism, a tendency towards reduction in the homeostasis model assessment (HOMA)-R (for insulin resistance) and HOMA-F (for beta cell function) was detected. In addition, an increase in the levels of C peptide during oGTT was observed (P<0.01). CONCLUSIONS: Long-term metformin treatment reduced various steroid enzymatic activities both in the ovary and the adrenal glands, without apparent changes in basal steroid levels and in insulin sensitivity.
The aim of this study was to investigate the effect of 7-oxo-DHEA (dehydroepiandrosterone) on the serum levels of steroid sexual hormones, gonadotropins, lipids and lipoproteins in men. 7-oxo-DHEA was applied onto the skin as a gel to 10 volunteers aged 27 to 72 years for 5 consecutive days. The single dose contained 25 mg 7-oxo-DHEA. Serum concentrations of testosterone, estradiol, cortisol, androstenedione, luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone binding globulin (SHBG), total cholesterol, HDL- and LDL-cholesterol, triglycerides, apolipoprotein A-I and B and lipoprotein(a) were measured before the beginning and shortly after the end of the steroid application. After the treatment, we noted the following significant changes: a decline of testosterone and estradiol levels, increase of LH, HDL-cholesterol and apolipoprotein A-I levels. The decrease of total cholesterol levels was of the borderline significance. A slight but significant increase was found in apolipoprotein B and lipoprotein(a). The most expressive was the fall of the atherogenic index. We suggest that the gel containing 7-oxo-DHEA might be a suitable drug for improving the composition of the steroid and lipid parameters in elderly men.
OBJECTIVE: In girls with Turner's syndrome a positive effect of growth hormone (GH) therapy on statutal growth has been well documented, in spite of the fact that the levels of GH and IGF-I in these patients are usually within the normal range. It is known that plasma levels of sex hormone-binding globulin (SHBG) are negatively associated with growth hormone (GH) and with [GF-I. Limited data on SHBG levels in these patients and only scarce reports on other than gonadal steroids in these patients are available so far. The major aim of this study was to find out whether SHBG does respond to GH treatment. METHODS: Plasma levels of SHBG, estradiol, progesterone, testosterone and the adrenal steroids and their precursors, namely cortisol, 17alpha-hydroxyprogesterone, androstenedione, dehydroepiandrosterone and its sulfate were determined in 65 patients aged 2-23 years with Turner's syndrome. The patients were divided into 4 groups according to their actual treatment (untreated, sex steroids only, GH only, GH and sex steroids) and the differences between the groups were evaluated. With respect to dependence of SHBG and of steroids studied on age (with exception of cortisol), their values were expressed as per cents of medians of the physiological values. RESULTS: As expected, low levels of sex steroids were found. As to the adrenal steroids, in general, their average levels were lower than in healthy subjects but still within the physiological limits. With one exception (androstenedione), no significant differences were found between the groups. The levels of cortisol were undistinguishable from healthy subjects. Absolute as well as relative SHBG levels in untreated group and in the group treated with estrogens were normal or even lower than those reported for normal subjects of the same chronological age. Significantly reduced absolute as well as relative SHBG levels in comparison to all other groups were found in GH treated children. CONCLUSION: The results indicate that SHBG may serve as a sensitive biochemical marker of the response to the GH administration.
A common variant of the LHbeta subunit has a varying prevalence in various ethnic groups. The consequences of the presence of mutated luteinizing hormone (LH) concern borderline alterations in pituitary/gonadal function that could be mediated by an altered action of variant LH on gonadal steroidogenesis. A comparison of plasma concentrations of gonadal steroid sex hormones was completed in women heterozygous for variant LH and in women with the wild type of LH in three different age ranges. The sample was a randomly selected group of 177 normal women 16 to 72 years old. Variant LH was determined by immunofluorimetric methods using two combinations of monoclonal antibodies. The ratios of LH measured by the two assays indicated whether the subject was wild type homozygote, heterozygote or homozygote for the variant LHbeta allele. The carriers of the variant LH allele in the group of postmenopausal women showed higher serum testosterone levels than those with the wild type LH. This is in agreement with the clinical observations made previously showing a slightly higher androgenic action in the population with variant LH. No differences were detected in serum LH, FSH, epitestosterone and sex hormone binding globulin (SHBG).
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Today within the United States, CVD is the leading cause of death in women with the highest mortality being seen in African-American women. A review of literature revealed that over the last decade, within the United States, there has been an overall reduction in the death rate due to CVD. However, the rate of decline has been less for women than for men and less for African-American women than for White women. Findings from some studies indicate that African-American women have increased risk factors as compared to other ethnic groups for CVD based upon conditions and behaviors affecting lifestyle. Fortunately, most of the CVD risk factors are modifiable and their occurrence can be widely prevented. Therefore, it is imperative that health care providers approach the issue of risk factors for CVD in African-American women as a heart disease epidemic. This approach is necessary if the United States is going to improve the health of all Americans, eliminate disparities, and improve the quality of life.
Seminal fluid represents a milieu enabling spermatozoa to break the ovum membrane and suppress its immune response and, at the same time, to protect male germ cells against infection. Among constituents of the seminal fluid, various steroids, including dehydroepiandrosterone (DHEA) and its sulphate, were detected. With respect to immunomodulatory and antioxidative properties of the latter steroid and its 7-hydroxylated metabolites, believed to be at least in some instances the locally active species, their presence in seminal fluid is of particular interest. Here for the first time unconjugated 3beta,7alpha-dihydroxy-5-androsten-17-one (7alpha-OH-DHEA) and its 7beta-hydroxyisomer have been detected and quantified in semen. Eight semen samples were extracted with diethyl ether and following evaporation and solvent partition both isomers were detected by gas chromatography-mass fragmentometry using the ions m/z 358 and 343 for quantification. Another portion was separated by HPLC and in the fractions corresponding to 7-OH-DHEA isomers the steroids were measured by recently developed specific radioimmunoassays (RIA). Mean concentrations of 7-OH-DHEA as measured by RIA amounted 5.75+/-1.29 and 5.39+/-0.75 nmol/l (mean+/-SEM) for 7alpha- and 7beta-OH-DHEA, respectively.
A rapid method for the identification and measurement of four pregnanolone isomers and their polar conjugates in human plasma was developed using a simple quadrupole GC/MS system with electron impact ionization. Steroid levels were measured in the plasma of 13 and three women at delivery with subarachnoidal and epidural analgesia, respectively, and in corresponding samples of umbilical plasma. A good correlation (r=0.94, P<0.001, n=8) was found between the allopregnanolone in maternal plasma determined by GC/MS and that measured by RIA. Epipregnanolone (3beta-hydroxy-5beta-pregnan-20-one) was identified and measured for the first time in human plasma; its concentration in both maternal and umbilical plasma was much lower than that of other pregnanolone isomers. The levels of 3beta-hydroxy-pregnanolone isomers were significantly higher in the umbilical plasma than in the maternal plasma, while the differences in 3alpha-hydroxy-isomers were insignificant. The differences in conjugates were insignificant except in the case of allopregnanolone, the levels of which were lower in umbilical plasma. In all of the pregnanolone isomers, a significantly lower conjugated/unconjugated steroid ratio was found in the umbilical plasma than in the maternal plasma. The possible role of the sulfatation of pregnanolone isomers around parturition is discussed.
The true prevalence of müllerian duct abnormalities is not well established. We used standard ultrasound examinations to establish the prevalence of müllerian duct abnormalities in girls and women who were evaluated for reasons unrelated to the presence of uterine anomalies. Prospective ultrasound examinations for nonobstetric indications in 2,065 consecutive girls and women (aged 8-93) showed that 8 had anomalies, including bicornuate uterus, septate uterus, and double uterus. In this first attempt to determine the prevalence of uterine anomalies in the general population, using noninvasive methodology, the rate of anomalies was 3.87 per 1,000 women (exact 95% confidence interval: 1.67-7.62), or approximately 1 in 250 women. This prevalence estimate may be greater than the true rate if selection biases are strong, or less than the true prevalence if ultrasound detection rates are low. As a first attempt to establish the prevalence by pelvic ultrasound in a consecutive series, these data may serve as a baseline estimate.
Four important changes have been introduced in the revised guidelines for the management of women with abnormal cervical smears, 1998. 1. For the purposes of management, atypical squamous cells of undetermined significance (ASCUS) and atypical glandular cells of undetermined significance (AGUS) have been included with low grade squamous intraepithelial lesions (LSIL/CIN1/HPV) except where the smear raises the possibility of a high grade squamous intraepthelial lesion (HSIL) or favours glandular dysplasia. 2. Women with low grade cytological and histological intraepithelial abnormalities will, after initial follow-up, revert to three yearly screening. 3. Requirements for those practising colposcopy have been defined. 4. A formal review of all cases of invasive cervical cancer is advocated.
We have used bidirectional transfer methods in concert with SMART total cDNA complex probes to sequentially screen differential display arrays. In this report we show the utility of this methodology in examining a manganese superoxide dismutase cDNA fragment which we detected while evaluating the effects of the proinflammatory cytokines IL1-beta, TNF-alpha, and IL6 on human umbilical vein endothelial cell (HUVEC) gene expression. By using parallel hybridization of the bidirectional blots with SMART total cDNA (32)P probes derived from untreated or cytokine-treated HUVECs, differential expression between cell treatments can be clearly evaluated. Subsequent screening using this bidirectional blot method results in detection of modulated cDNA clones. Northern and total cDNA blot hybridization with the cDNA clonal fragment confirmed both modulated expression and the efficacy of this screening method. These procedures allow one to use bidirectional blots to evaluate band modulation on agarose gels which are initially run to evaluate the reamplification of display fragments or to confirm cloned cDNA fragments. Thus, bidirectional blot analysis using SMART total cDNA probes allows direct evaluation of differential display bands from the initial reamplification through plasmid insert cloning, increasing the investigator's ability to eliminate false-positive bands during each step of analysis.
Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 3 genes that are homologous to cellular chemokines. vMIP-III, the product of open reading frame K4.1, is the most distantly related to human chemokines and has yet to be characterized. We have examined the interaction of vMIP-III with chemokine receptors, its expression in KS lesions, and its in ovo angiogenic properties. We show expression of vMIP-III in KS lesions and demonstrate the stimulation of angiogenesis by this chemokine, like vMIP-I and vMIP-II, in the chick chorioallantoic membrane assay. vMIP-III does not block human immunodeficiency virus entry through the coreceptors CCR3, CCR5, or CXCR4. However, vMIP-III is an agonist for the cellular chemokine receptor CCR4. CCR4 is expressed by TH2-type T cells. Consistent with this, vMIP-III preferentially chemoattracts this cell type. Because of these biologic properties and because it is expressed in KS lesions, vMIP-III may play an important role in the pathobiology of KS. (Blood. 2000;95:1151-1157)
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