HRT and everyday memory at menopause: A comparison of two samples of mid-aged women

Research on the effect of hormone replacement therapy (HRT) on memory in mid-aged women is equivocal although findings indicate that oestrogen may enhance verbal memory. Mood may mediate the relationship between HRT and memory. This study examined the effect of HRT on mood and everyday memory in two samples of women between ages 40 and 60 years. In the cross-sectional comparison (N = 124), HRT users performed significantly better on tests of everyday and verbal memory. A within-woman comparison of 17 women showed that everyday memory, working memory, and delayed verbal memory improved after 3 months of HRT use. The improvement in memory was not mediated by mood. These results suggest that any effect of HRT on mood may be short-term but that some aspects of everyday memory are enhanced, particularly verbal memory. The development of the everyday memory construct and future investigation are discussed.

Endocrine-disrupting compounds: A review of their challenge to sustainable and safe water supply and water reuse

The relevance of endocrine-disrupting compounds as potential contaminants of drinking water is reviewed, particularly in the reuse of wastewater. Growing populations and increasing intensification of land and water use for industry and agriculture have increased the need to reclaim wastewater for reuse, including to supplement the drinking water supply. The variety of anthropogenic chemicals that have been identified as potential endocrine disruptors in the environment and the problems arising from their use as human and livestock pharmaceuticals, as agricultural chemicals and in industry are discussed. The potentially adverse impact of these chemicals on human health and the ecology of the natural environment are reviewed. Data for the removal of estrogenic compounds from wastewater treatment are presented, together with the comparative potencies of estrogenic compounds. The relative exposure to estrogens of women on oral contraceptives, hormone replacement therapy, and through food consumption is estimated. A brief overview of some methods available or under development for the assessment of estrogenic activity in environmental samples is provided. The review concludes with a discussion of the directions for further investigation, which include human epidemiology, methodology development, and wastewater monitoring. (C) 2006 Wiley Periodicals, Inc.

Change in lean body mass Is a major determinant of change in areal bone mineral density of the proximal femur: A 12-year observational study

Our objective was to assess the contribution of lean body mass (LBM) and fat body mass (FBM) to areal bone mineral density (aBMD) in women during the years surrounding menopause. We used a 12-year observational design. Participants included 75 Caucasian women who were premenopausal, 53 of whom were available for follow-up. There were two measurement periods: baseline and 12-year follow-up. At both measurement periods, bone mineral content and aBMD of the proximal femur, posterior-anterior lumbar spine, and total body was assessed using dual-energy X-ray absorptiometry (DXA). LBM and FBM were derived from the total-body scans. General health, including current menopausal status, hormone replace therapy use, medication use, and physical activity, was assessed by questionnaires. At the end of the study, 44% of the women were postmenopausal. After controlling for baseline aBMD, current menopausal status, and current hormone replacement therapy, we found that change in LBM was independently associated with change in aBMD of the proximal femur (P = 0.001). The cross-sectional analyses also indicated that LBM was a significant determinant of aBMD of all three DXA-scanned sites at both baseline and follow-up. These novel longitudinal data highlight the important contribution of LBM to the maintenance of proximal femur bone mass at a key time in women's life span, the years surrounding menopause.

Controversies regarding the effects of growth hormone on the heart

Growth hormone (GH) profoundly affects the developing and adult myocardium. Adult patients with GH deficiency (GHD) and GH excess (acromegaly) provide important models in which to understand the effects of GH in adult cardiac physiology. An increasing body of clinical and experimental evidence illustrates the specific physiological abnormalities that are likely associated with the excess cardiovascular mortality observed in both acromegaly and GHD. Because human GH replacement is now available to treat adults with GHD, new questions emerge about the long-term cardiovascular effects of replacement therapy. In multiple trials, GH therapy for congestive heart failure has been proved ineffective in the absence of preexisting GHD. Case reports suggest that, in the setting of GHD, GH therapy can exert a potent beneficial effect on congestive heart failure. Long-term studies addressing cardiovascular morbidity and mortality are needed to assess the role of GH therapy for GHD.

Gonadotrophin and prolactin secretion in castrated male sheep following subcutaneous or intracranial treatment with testicular hormones

Interactions between testosterone, estradiol, and inhibin in the control of gonadotrophin secretion in males are poorly understood. Castrated rams were treated with steroid-free bovine follicular fluid (bFF), testosterone, or estradiol and for 7 d (2 x 2 x 2 factorial design). Given independently, none of the exogenous hormones affected follicle-stimulating hormone (FSH) concentrations, but the combination of one or both steroids with bFF reduced FSH secretion. Testosterone and estradiol reduced luteinizing hormone (LH) pulse frequency (there was no synergism), and bFF had no effect. Plasma prolactin concentrations were not affected by any treatment. To locate the central sites of steroid action, castrated rams were bilaterally implanted in the preoptic area (POA), ventromedial nucleus (VMH), or arcuate nucleus (ARC). These implants did not affect FSH or prolactin concentrations, or LH pulse amplitude. The frequency of the LH pulses was not affected by testosterone in any site. Estradiol located in the ARC, but not the POA or VMH, decreased LH pulse frequency. In summary, FSH secretion is controlled by synergistic interactions between inhibin and estradiol or testosterone, whereas GnRH/LH pulse frequency is controlled by testicular steroids. Estradiol acts partly, at least, in the ARC, but the central site of action, testosterone remains unknown.

Estrogen replacement, muscle composition, and physical function: The health ABC study

Purpose: Although the beneficial effects of estrogen use on cardiovascular and cognitive function in postmenopausal women have been recently discredited, controversy remains regarding its usefulness for maintaining skeletal muscle mass or strength. Therefore, the purpose of this study was to determine whether estrogen use is associated with enhanced muscle composition and, if so, whether this translates into improved strength and physical function. Methods: Cross-sectional analysis of 840 well-functioning community-dwelling white women (current estrogen replacement therapy (ERT) users = 259, nonusers = 581) aged 70-79 yr participating in the Health, Aging and Body Composition Study. Muscle composition of the midthigh by computed tomography included cross-sectional area (CSA) of the quadriceps, hamstrings, intermuscular fat and subcutaneous fat, and muscle attenuation in Hounsfield units (HU) as a measure of muscle density. Isometric hand grip and isokinetic knee extensor strength were assessed by dynamometry. Physical function was assessed using a summary scale that included usual 6-m walk and narrow walk speed, repeated chair stands, and standing balance. Results: In analyses of covariance adjusted for relevant confounders. quadriceps muscle CSA and HU were greater in Current ERT than non-ERT women (P < 0.05). Grip strength was also greater (P < 0.05) in women taking ERT while knee extensor strength approached significance (P < 0.10). However, differences in muscle composition and strength were modest at <= 3.3%. There was no difference by ERT status for the hamstring, muscles. fat CSA. or for physical function. Conclusion: The associations between ERT and muscle composition and strength were minor and did not translate into improved physical function. Initiation of ERT for preservation of muscle composition and function may not be indicated.

The prospects for immunotherapy in smoking cessation

Context Smoking is a major preventable cause of death and disability that is maintained by dependence on nicotine. Smoking cessation reduces mortality and morbidity. Although existing pharmacological aids to smoking cessation and relapse prevention (nicotine replacement therapy and bupropion) improve on unassisted quitting and behavioural methods, they are only modestly effective. More effective pharmacological methods are required that improve compliance, reduce side-effects, and can be used in combination with existing cessation methods. Starting point A nicotine vaccine is a promising immunotherapeutic approach to smoking cessation and relapse prevention. Such a vaccine would induce the immune system to form specific antibodies to nicotine to prevent it from crossing the blood-brain barrier to act on receptor sites in the central nervous system. Recent studies in rats provide proof of principle by showing that nicotine-specific antibodies can prevent the reinstatement of nicotine self-administration (N Lindblom et al, Respiration 2002; 69: 254–60) and block dopamine release in the shell of the nucleus accumbens (Sde Villiers et al, Respiration 2002; 69: 247–53). A phase 1 trial of a human cocaine vaccine has also recently been successfully completed (T Kosten et al, Vaccine 2002; 20: 1196–204). A safe and effective human nicotine vaccine would potentially have fewer side-effects and better compliance than existing smoking-cessation pharmacotherapies. It could also be used in combination with some of them (eg, bupropion). Where next? The most promising clinical application of a human nicotine vaccine is likely to be in relapse prevention in abstinent smokers. A vaccine may also have a role in preparing smokers to quit. Clinical trials of safety and efficacy in human smokers and ex-smokers are warranted. If a nicotine vaccine proves to be safe and effective, the health-care system will need to ensure that it is registered for clinical use and that the poorer members of the community (among whom smoking prevalence is now highest in developed countries) have access to the vaccine. The community will need to be appropriately informed about the role of a nicotine vaccine to ensure that it is not prematurely used for preventive purposes in children and adolescents.

Effect of estrogen on vascular smooth muscle cells is dependent upon cellular phenotype

To investigate the growth-regulating action of estrogen on vascular smooth muscle cells (SMC), effects of beta-17-estradiol (beta-E-2) on phenotypic modulation and proliferation of rabbit aortic SMC were observed in vitro. At 10(-8) M, beta-E-2 significantly slowed the decrease in volume fraction of myofilaments (V(v)myo) of freshly dispersed SMCs in primary culture, indicating an inhibitory effect of beta-E-2 On spontaneous phenotypic modulation of SMC from a contractile to a synthetic phenotype. Freshly dispersed SMCs treated with beta-E-2 also had a relatively longer quiescent phase than control cells before intense proliferation occurred. This was in contrast to SMCs in passage 2-3 (synthetic state), where beta-E-2-treated cells replicated significantly faster than untreated cells. beta-E-2 also markedly enhanced the serum-induced DNA synthesis of synthetic SMCs in a concentration-dependent manner within physiological range (10(-10) to 10-8 M). These findings indicate that the growth-regulating effect of estrogen on vascular SMC is dependent on the cell's phenotypic stare. It delays the cell cycle re-entry of the contractile SMCs by retarding their phenotypic modulation however, once cells have modulated to the synthetic phenotype, it promotes their replication. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.

Polymorphisms of the renin-angiotensin system in patients with multifocal renal arterial fibromuscular dysplasia

Fibromuscular dysplasia (FMD) is an important cause of renal artery stenosis, particularly in young females. Polymorphisms of the renin-angiotensin (RA) system have been implicated in the pathogenesis of hypertension and atherosclerotic vascular disease, and may play a role in the development of FMD. Examination of polymorphisms by PCR for angiotensin-converting enzyme (ACE) I/D, angiotensin II type 1 receptor (AT(1)R) A1166C and angiotensinogen (AGT) M235T and T174M was undertaken in 43 patients with typical multifocal renal arterial FMD (MF-FMD) and in 89 controls. The age of NIF-FMD patients at the time of diagnosis of hypertension did not differ (38.6 + 11.1 years vs 35.5 +/- 10.3 years, P = 0.12) from controls and the proportion (95% vs 86%, P = 0.14) of females was similar. Allele frequencies did not differ significantly between groups, except that MF-FMD patients had a significantly higher frequency of the ACE I allele than control subjects (0.62 vs 0.47, P = 0.026). Since the ACE I allele is associated with lower circulating ACE levels and possibly lower tissue levels of angiotensin II (Ang II), and since Ang II modulates vascular smooth muscle cell growth and synthetic activity, the I allele might predispose to defective remodelling of the arterial media, and thus to the development of MF-FMD. This contrasts with atherosclerotic renal artery stenosis, coronary stent restenosis and carotid intimal thickening, which are diseases affecting the arterial intima, and which are associated with increased frequency of the D allele.

Pharmacokinetics of ciprofloxacin in ICU patients on continuous veno-venous haemodiafiltration

Objectives: To investigate the pharmacokinetics of intravenous ciprofloxacin 200 mg every 8 h in critically ill patients on continuous veno-venous haemodiafiltration (CVVHDF), one form of continuous renal replacement therapy (CRRT). Design and setting: Open, prospective clinical study in a multidisciplinary, intensive care unit in a university-affiliated tertiary referral hospital. Patients: Sis critically ill patients with acute renal failure on CVVHDF. Interventions: Timed blood and ultrafiltrate samples were collected to allow pharmacokinetics and clearances to be calculated of initial and subsequent doses of 200 mg intravenous ciprofloxacin. CVVHD was performed with 1 l/h of dialysate and 2 l/h of predilution filtration solution, producing 3 lih of dialysis effluent. The blood was pumped at 200 ml/min using a Gambro BMM-10 blood pump through a Hospal AN69HF haemofilter,. Measurements and results: Ten pharmacokinetic profiles were measured. The CVVHDF displayed a urea clearance of 42 +/- 3 ml/min, and removed ciprofloxacin with a clearance of 37 +/- 7 ml/min. This rate was 2-2.5 greater than previously published for ciprofloxacin in other forms of CRRT. On average the CVVHDF was responsible for clearing a fifth of all ciprofloxacin eliminated (21 +/- 10%). The total body clearance of ciprofloxacin was 12.2 +/- 4.3 l/h. The trough concentration following the initial dose was 0.7 +/- 0.3 mg/l. The area under the plasma concentration time curves over a 24-h period ranged from 21 to 55 mg .h l(-1). Conclusions: Intravenous ciprofloxacin 600 mg/day in critically ill patients using this form of CRRT produced adequate plasma levels for many resistant microbes found in intensive care units.

The effectiveness of personalized smoking cessation strategies for callers to a Quitline service

Aim To assess the effectiveness of a program of computer-generated tailored advice for callers to a telephone helpline, and to assess whether it enhanced a series of callback telephone counselling sessions in aiding smoking cessation. Design Randomized controlled trial comparing: (1) untailored self-help materials; (2) computer-generated tailored advice only, and (3) computer-generated tailored advice plus callback telephone counselling. Assessment surveys were conducted at baseline, 3, 6 and 12 months. Setting Victoria, Australia. Participants A total of 1578 smokers who called the Quitline service and agreed to participate. Measurements Smoking status at follow-up; duration of cessation, if quit; use of nicotine replacement therapy; and extent of participation in the callback service. Findings At the 3-month follow-up, significantly more (chi(2)(2) = 16.9; P < 0.001) participants in the computer-generated tailored advice plus telephone counselling condition were not smoking (21%) than in either the computer-generated advice only (12%) or the control condition (12%). Proportions reporting not smoking at the 12-month follow-up were 26%, 23% and 22%, respectively (NS) for point prevalence, and for 9 months sustained abstinence; 8.2, 6.0, and 5.0 (NS). In the telephone counselling group, those receiving callbacks were more likely than those who did not to have sustained abstinence at 12 months (10.2 compared with 4.0, P < 0.05). Logistic regression on 3-month data showed significant independent effects on cessation of telephone counselling and use of NRT, but not of computer-generated tailored advice. Conclusion Computer-generated tailored advice did not enhance telephone counselling, nor have any independent effect on cessation. This may be due to poor timing of the computer-generated tailored advice and poor integration of the two modes of advice.

The effect of adsorption, filter material and point of dilution on antibiotic elimination by haemofiltration - An in vitro study of levofloxacin

We studied an in vitro model of continuous venous-venous haemofiltration (CVVH), into which levofloxacin 100 mg was infused, to determine levofloxacin adsorption and to determine the effect of filter material and point of dilution (pre- or post-filter) on sieving coefficient. Mean (standard deviation; S.D.) adsorption was 18.7 (5.3) mg for the polyamide filter and 40.2 (2.0) mg for the polyacrylonitrile (PAN) filter (P < 0.001). Post-dilution resulted in a minor, but statistically significant, decrease in sieving coefficient (pre-dilution 0.96 (S.D. 0.10), post-dilution 0.88 (S.D. 0.11) with the PAN filter. These data indicate that the variability in published values for levofloxacin sieving coefficient are not due to variation in point of dilution or membrane type (PAN or polyamide). Significant adsorption of levofloxacin onto PAN filters occurs. (C) 2004 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Benign intracranial hypertension associated with acromegaly

This is the first reported case of benign intracranial hypertension (BIH) occurring with acromegaly and resolving after successful treatment of a growth hormone-secreting pituitary adenoma. BIH has been reported with recombinant human growth hormone (rhGH) therapy of GH deficient patients and insulin-like growth factor I (IGF-I) treatment of growth hormone (GH) insensitivity (Laron syndrome) in children. We postulate that the proposed mechanism causing BIH in rhGH-treated children and in acromegaly results from increased cerebrospinal fluid production from the choroid plexi secondary to elevated cerebrospinal fluid growth hormone concentrations that trigger local IGF-I secretion and activation of IGF-I receptors.