Inhibin-A in Down's syndrome pregnancies: revised estimate of standard deviation.
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Biomedical subjects
Publications and source records attributed to L George.
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This paper reviews research on the psychological characteristics of patients suffering from anorexia nervosa and that examining the therapeutic relationship. The former research suggests that anorexic patients possess a psychological profile characterized by: a phobia of weight gain and fear of loss of control; alexithymia and lack of introceptive awareness; mistrust of self and others; cognitive dysfunction; low self-esteem; and often the presence of starvation-induced depression. The latter strongly suggests that in order for a relationship to be therapeutic it needs to be characterized by: empathy; positive regard and acceptance; warmth; commitment; trust; genuineness; and be non-judgemental. The implications of these research findings regarding the nurse's role in forming a therapeutic relationship with anorexic patients is then discussed. It is seen that it is vital that nurses receive adequate education before working with such patients, and that their knowledge is regularly updated. Nurses should receive regular clinical supervision and support, in order to ensure that they are able to provide therapeutic care for such patients.
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The value of measuring inhibin-A (a beta A dimer) with human chorionic gonadotrophin (total or the sub-units free a-hCG and free beta-hCG separately), alpha-fetoprotein (AFP), and unconjugated oestriol (uE3) was examined to determine the effect on the performance of serum screening for Down's syndrome between 15 and 22 weeks of pregnancy. The study was based on stored serum samples from 77 Down's syndrome singleton pregnancies and 385 unaffected singleton pregnancies, matched for maternal age, gestational age, and duration of storage of the sample, supplemented by data from 970 white women with unaffected pregnancies. Inhibin-A was elevated in the serum of women with Down's syndrome pregnancies with a median of 1.79 multiples of the median (MOM). Using the four serum markers AFP, uE3, total hCG, and inhibin-A, in addition to maternal age, 70 per cent of Down's syndrome pregnancies were detected for a 5 per cent false-positive rate compared with 59 per cent with the conventional triple test (AFP, uE3, and total hCG with maternal age). If the estimate of gestational age were based on an ultrasound scan examination, the detection rate would be 77 per cent [95 per cent confidence interval (CI) 69-85 per cent] using the four serum markers including inhibin-A, compared with 67 per cent with the triple test or 79 per cent (95 per cent CI 71-87 per cent) if marker values were adjusted for maternal weight. If the detection rate were kept at 70 per cent and the gestational age were estimated by an ultrasound scan examination, the four-marker test would reduce the false-positive rate from 6-1 per cent using the triple test to 2-9 per cent. The results were virtually the same if free beta-hCG was used instead of total hCG. The inhibin-A-based four-marker test is the most effective method of prenatal screening for Down's syndrome suitable for routine use. If the extra cost required to carry out the inhibin-A test were less than about [symbol: see text]3 per woman screened, the four-marker test including inhibin-A would be financially cost-effective.
A nested case-control study using stored serum samples collected as part of a prospective study of the outcome of pregnancy was performed to investigate concentrations of (dimeric) inhibin-A in maternal serum between 15 and 22 weeks of pregnancy in 126 pregnancies among 92 women with insulin-dependent diabetes mellitus (IDDM). Each IDDM pregnancy was matched with two control singleton pregnancies for gestational age (same completed week) and duration of sample storage (same calendar quarter). The median inhibin-A level in the IDDM pregnancies was 0.88 multiples of the median (MOM) for pregnancies without IDDM at the same gestational age (P = 0.05) (95 per cent confidence interval 0.78-1.00) or 0.91 MOM after adjustment for maternal weight. These results enable inhibin-A values to be adjusted so that prenatal screening for Down's syndrome can be performed using this marker in IDDM pregnancies as well as in non-diabetic pregnancies.
A nested case-control study using stored serum samples collected as part of a prospective study of the outcome of pregnancy was performed to investigate concentrations of (dimeric) inhibin-A in maternal serum between 15 and 22 weeks of pregnancy in 200 twin pregnancies and 600 singleton control pregnancies. Each twin pregnancy was matched with three singleton pregnancies for gestational age (same completed week) and duration of sample storage (same calendar year), although for one twin there was insufficient serum. The median inhibin-A level in the twin pregnancies was 1.99 multiples of the median (MOM) for singleton pregnancies (P < 0.001) [95 per cent confidence interval (CI) 1.83-2.16]. These results enable inhibin-A values to be adjusted so that prenatal screening for Down's syndrome can be performed using this marker in twin pregnancies as well as in singleton pregnancies.
OBJECTIVE: To determine the value of serum screening for Down's syndrome at 8-14 weeks of pregnancy using seven potential serum markers (alpha-fetoprotein, unconjugated oestriol, total human chorionic gonadotrophin (hCG), free alpha-hCG, free beta-hCG, pregnancy associated plasma protein A (PAPP-A), and dimeric inhibin A). DESIGN: Stored blood samples collected from women at about 10 weeks of pregnancy, prior to having chorionic villus sampling procedure on account of advanced maternal age, were retrieved from pregnancies associated with Down's syndrome and from matched unaffected pregnancies. SETTING: Twenty-one obstetric centres in nine countries. SUBJECTS: Seventy-seven pregnancies associated with Down's syndrome each matched with five controls (except in two cases that were matched with four controls) for maternal age (same five year age groups), duration of storage of the serum sample (same calendar year), and gestational age (usually same week of pregnancy). RESULTS: The levels of two potential markers differed between affected and unaffected pregnancies sufficiently to be of value in screening--free beta-hCG and PAPP-A. The median free beta-hCG level in affected pregnancies was 1.79 times the median level for unaffected pregnancies, and the median PAPP-A level was 0.43 times the normal median. These two markers were combined with maternal age to estimate a woman's risk of having a fetus with Down's syndrome. A screening programme that used a risk cutoff level of 1:300 would detect 63% of affected pregnancies and also classify 5.5% of unaffected pregnancies as screen positive. None of the other five markers added more than 2% detection for the same false-positive rate. CONCLUSION: The performance of screening using maternal age and serum-free beta-hCG and PAPP-A at 10 weeks of pregnancy was better than the double test (alpha-fetoprotein and hCG with maternal age) and similar to the triple test (alpha-fetoprotein, unconjugated oestriol and hCG with maternal age) at 15-22 weeks.
The main objective of this study was to determine whether activin A concentrations in peripheral blood fluctuate during the normal human menstrual cycle and pregnancy. Blood samples were collected longitudinally from five regularly cycling volunteers (22-30 yr) throughout a spontaneous menstrual cycle and cross-sectionally from normal pregnant women attending the antenatal clinic (8-38 weeks gestation: 3-20 subjects/time point). Total (i.e. bound plus free) activin A concentrations were measured using a recently developed two-site enzyme immunoassay that employs an analyte denaturation/oxidation step to eliminate interference due to endogenous activin-binding proteins. During the menstrual cycle, mean serum activin A levels varied in a biphasic manner (by ANOVA, P = 0.02), with highest levels around midcycle (approximately 220 pg/mL) and the late luteal/early follicular phase (approximately 310 pg/mL) and nadirs in both midfollicular (approximately 125 pg/mL) and midluteal (approximately 120 pg/mL) phases. Between the mid- to late luteal phase, the activin A level increased progressively (approximately 2.5-fold; P < 0.05), whereas inhibin A, estradiol, and progesterone all decreased progressively (approximately 10-fold; P < 0.001). During pregnancy, serum activin A levels were much higher than those in nonpregnant subjects, with a value of 2.12 +/- 0.31 ng/mL recorded in week 8. Levels remained at approximately 2 ng/mL between weeks 8-24, but increased thereafter to reach 25.5 +/- 6 ng/mL by week 38, a value approximately 100 times greater than that during the normal menstrual cycle. Serum activin A levels during pregnancy were significantly correlated with inhibin A (r = 0.69; P < 0.001), estradiol (r = 0.55; P < 0.001), and progesterone (r = 0.74; P < 0.001) values. Gel permeation chromatography indicated that all of the detectable activin A in human follicular fluid, pregnancy serum, and term placental extract eluted with an apparent molecular mass between 70-200 kDa, indicating that little, if any, free activin (molecular mass, 25 kDa) is present in these samples. Although these results support a possible endocrine role for circulating activin A during the human menstrual cycle and pregnancy, the observation that all detectable activin A is associated with binding protein(s) raises questions about its relative bioavailability for action on peripheral target cells.
OBJECTIVE: To determine whether urinary magnesium (Mg) values in patients with gut failure would be more helpful than serum Mg measurements in assessment of Mg deficiency. DESIGN: We compared serum and urinary Mg values in 16 patients with gut failure and 16 age- and sex-matched control subjects. MATERIAL AND METHODS: Sixteen patients with gut failure (nine women and seven men; mean age, 59 years) had serum and 24-hour urinary mg measured before Mg replacement therapy. Short bowel syndrome was present in 75%, and diffuse small bowel disease was present in 25%. RESULTS: The median value for serum Mg was 1.7 mg/dL for patients and 2.0 mg/dL for healthy control subjects (P < 0.001). The median values for urinary Mg were 19 mg and 127 mg per 24-hour specimen in patient and control groups, respectively (P < 0.001). A strong correlation was noted between serum Mg and urinary Mg levels. All patients had low urinary Mg values even though 9 of 16 (56%) had normal serum Mg values. Two patients with normal serum Mg concentrations had urinary Mg values of 20 mg/24 h (25% of normal). Serum, but not urinary, Mg correlated significantly with the length of remaining small bowel (P = 0.03). CONCLUSIONS: Urinary Mg declines before serum Mg and is an earlier and more reliable indicator of evolving Mg deficiency. On the basis of these observations and those showing beneficial effects of parenterally administered Mg supplements on urinary citrate excretion (and, presumably, formation of calcium oxalate stones), replacement of Mg in patients with gut failure should be targeted at normalizing urinary Mg.
OBJECTIVE: To evaluate measurement of serum prostate specific antigen as a potential screening test for future clinical prostate cancer among healthy men. DESIGN: Nested case-control study with stored serum samples collected from 49,261 men with follow up using national death and cancer registration systems. SUBJECTS: 265 asymptomatic men who subsequently developed clinical prostate cancer and 1055 controls matched for age, study centre, and duration of storage of samples. MAIN OUTCOME MEASURES: Distribution of concentrations of the antigen in men who developed prostate cancer and in controls. RESULTS: Prostate specific antigen concentrations were significantly higher in men who subsequently developed prostate cancer than in controls. In the first three years after blood collection the median concentration was 23 times greater in cases than in controls of the same age at the same centre (that is, 23 multiples of the median). A smaller difference persisted thereafter; 4.0 multiples of the median 3-6 years after blood collection, 3.6 6-10 years, and 1.8 after 10 years. In the first three years the proportion of men who developed prostate cancer and had raised levels of the antigen (> or = 12 multiples of the median) (detection rate or sensitivity) was 81% (95% confidence interval 54% to 96%). The proportion of men who did not develop prostate cancer but had levels this high (false positive rate) was only 0.5%. CONCLUSION: Prostate specific antigen measurement is a highly discriminatory screening test for prostate cancer among healthy men. In the general population, 60-74 year old men who had > or = 12 times the normal median level would have about a 50% chance of developing clinical prostate cancer in the next three years. Measurement of this antigen is a good enough screening test to justify a randomised controlled trial to determine any reduction in mortality from prostate cancer.
Previous studies have found lower mortality rates for AIDS-related Pneumocystis carinii pneumonia (PCP) in hospitals with higher levels of experience with PCP. It is not known if patients are selectively referred to better hospitals or if there is a learning curve whereby outcomes improve as physicians gain experience in treating PCP. We assessed cases of PCP at 140 Veterans Administration (VA) Medical Centers in the United States. During 1987-1991, 3,981 patients were hospitalized with first-episode AIDS-related PCP. Mortality at 30 days after admission. For these 3,981 hospitalizations at the 140 study hospitals, the 30-day mortality was 19%. Logistic regression models indicate that older age, race, geographic area, earlier year of treatment, hospitalization in the previous 12 months, and lower levels of hospital experience with AIDS were significant predictors of mortality at 30 days after admission. Compared with hospitals that had treated three cases or fewer of first-episode PCP, the odds of mortality at 30 days at hospitals that treated > 50 cases of first-episode PCP were 0.73 (95% confidence interval 0.58-0.91), after controlling for differences in characteristics of the patients, year, and region. Mortality of patients with AIDS-related PCP decreases as VA hospitals gain experience. Longitudinal analyses over a 5-year period suggest that a learning curve best explains this finding.
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Pulmonary artery distortion is a risk factor among candidates for the Fontan procedure. In 57 patients evaluated by catheterization after successful cavopulmonary anastomosis, 8 had proximal left pulmonary artery (LPA) stenosis, either discrete (4 patients) or long segment (4 patients). Median age was 27 months (range 19 to 60 months). Median weight was 11.4 kg (range 9.1 to 20.0). Mean diameter at LPA stenosis was 4.4 +/- 0.4. Proximal right pulmonary artery mean diameter was 10.4 +/- 1.0 mm. After angiographic and hemodynamic assessment, short 11F sheaths were placed in the right internal jugular (6 patients) or subclavian veins (2 patients). Pulmonary artery angioplasty and stent placement were performed. LPA stenoses were enlarged using 10 Palmaz stents dilated to 10 mm (7 patients) or to 12 mm (3 patients). Poststent angiograms showed that narrowest LPA dimensions were significantly enlarged to 9.9 mm +/- 1.0 mm, p < 001). There were no complications. Follow-up studies (catheterizations in 4 patients, echocardiograms in 8 patients) were performed 4 to 9 months after stent implantation. No restenosis was observed. Five patients had completion of their Fontan procedures; three patients are pending Fontan completion. This study demonstrates the efficacy and safety of the percutaneous use of Palmaz stents to correct pulmonary artery stenosis in young children after cavopulmonary anastomosis.
OBJECTIVE: The aims were to measure concentrations of inhibin-A (alpha-beta A dimer) in peripheral serum during normal human pregnancy, to establish which molecular weight form(s) are present in pregnancy serum and to relate the concentrations of inhibin-A to those of oestradiol and progesterone. DESIGN: In a retrospective cross-sectional study 211 serum samples collected at 2-week intervals from week 8 to 38 of gestation were analysed for inhibin-A by enzyme immunoassay and oestradiol and progesterone by radioimmunoassay. Pooled samples corresponding to first, second and third trimester were subsequently used for fast protein liquid chromatography chromatographic analysis of inhibin forms present. PATIENTS: Blood samples were obtained from normal pregnant women attending the antenatal clinic. RESULTS: Concentrations of inhibin-A in peripheral serum gradually decreased from 1.76 +/- 0.15 microgram/l in week 8 of gestation to 0.86 +/- 0.12 microgram/l in week 16 (P < 0.01). Concentrations remained low during the second trimester but increased markedly (P < 0.01) during the third trimester reaching a maximal value of 5.68 +/- 0.89 microgram/l in week 36. Chromatographic analysis of pooled serum samples from the first, second and third trimester showed that the fully processed 31-kDa molecule is the predominant circulating form of inhibin-A throughout human gestation. Likewise, only the 31-kDa form was identified in extracts of term placenta which contained approximately 20 micrograms inhibin-A/kg tissue. CONCLUSION: Inhibin-A, principally the 31-kDa form, is present in peripheral blood throughout human gestation at concentrations up to 50 times greater than maximum values found during the spontaneous menstrual cycle (approximately 100 ng/l). The finding of highest serum values during the third trimester and of significant concentrations in term placenta firmly support a placental rather than luteal origin for this material.
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The Military Health Service System (MHSS) provides health care for the Department of Defense (DOD). This system operates on an annual budget of $15 Billion, supports 127 medical treatment facilities (MTFs) and 500 clinics, and provides support to 8.7 million beneficiaries worldwide. To support these facilities and their patients, the MHSS uses more than 125 different networked automated medical systems. These systems rely on a heterogeneous telecommunications infrastructure for data communications. With the support of the Defense Medical Information Management (DMIM) Program Office, our goal was to identify the network requirements for DMIM migration and target systems and design a communications infrastructure to support all systems with an integrated network. This work used tools from Business Process Reengineering (BPR) and applied it to communications infrastructure design for the first time. The methodology and results are applicable to any health care enterprise, military or civilian.
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