Daily salivary cortisol patterns in midlife women with hot flashes.

OBJECTIVE: Diurnal salivary cortisol patterns in healthy adults are well established but have not been studied in midlife women with hot flashes. We hypothesized that frequent hot flashes are associated with aberrant cortisol patterns similar to sleep-deficient individuals. DESIGN: Cross-sectional. PARTICIPANTS: A total of 306 women, ages 40-62, randomized to a behavioural intervention for hot flashes. MEASUREMENTS: Baseline comparisons of cortisol geometric means (nmol/l) from four daily time points averaged over two consecutive days plus other calculated cortisol measures were made between groups defined by baseline: (i) mean daily hot flash frequency tertile (≤5·5, N = 103; >5·5-8·8, N = 103; >8·8, N = 100) and (ii) selected characteristics. Repeated-measures linear regression models of log-transformed cortisol evaluated group differences, adjusting for covariates. RESULTS: Women were 67% White and 24% African American, with 7·6 (SD 3·9) hot flashes per day. Salivary cortisol geometric means (nmol/l) among all women were as follows: 75·0 (SD 44·8) total, 8·6 (SD 5·6) wake, 10·0 (SD 7·5) wake +30 min, 3·7 (SD 3·3) early afternoon and 1·6 (SD 1·8) bedtime. Wake + 30-minute values showed an 18% median rise from wake values (interquartile range -24 to 96%), and means varied by hot flash frequency tertile, from lowest to highest: 11·4(SD 7·3), 10·3 (SD 6·5) and 8·6 (SD 7·8), respectively, P = 0·003. Beside the early afternoon value (P = 0·02), cortisol values did not vary by hot flash frequency. CONCLUSION: Taken together, these findings suggest that high frequency of moderate-to-severe hot flashes may be associated with subtle abnormalities in cortisol concentrations - a pattern consistent with chronic sleep disturbance.

Decreased NAA in gray matter is correlated with decreased availability of acetate in white matter in postmortem multiple sclerosis cortex.

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the central nervous system (CNS) which leads to progressive neurological disability. Our previous studies have demonstrated mitochondrial involvement in MS cortical pathology and others have documented decreased levels of the neuronal mitochondrial metabolite N-acetyl aspartate (NAA) in the MS brain. While NAA is synthesized in neurons, it is broken down in oligodendrocytes into aspartate and acetate. The resulting acetate is incorporated into myelin lipids, linking neuronal mitochondrial function to oligodendrocyte-mediated elaboration of myelin lipids in the CNS. In the present study we show that treating human SH-SY5Y neuroblastoma cells with the electron transport chain inhibitor antimycin A decreased levels of NAA as measured by HPLC. To better understand the significance of the relationship between mitochondrial function and levels of NAA and its breakdown product acetate on MS pathology we then quantitated the levels of NAA and acetate in MS and control postmortem tissue blocks. Regardless of lesion status, we observed that levels of NAA were decreased 25 and 32 % in gray matter from parietal and motor cortex in MS, respectively, compared to controls. Acetate levels in adjacent white matter mirrored these decreases as evidenced by the 36 and 45 % reduction in acetate obtained from parietal and motor cortices. These data suggest a novel mechanism whereby mitochondrial dysfunction and reduced NAA levels in neurons may result in compromised myelination by oligodendrocytes due to decreased availability of acetate necessary for the synthesis of myelin lipids.

Clinical relevance of laboratory-reported antibiotic resistance in acute uncomplicated urinary tract infection in primary care.

OBJECTIVES: To determine whether patients with an uncomplicated community-acquired urinary tract infection (UTI) and an isolate resistant to trimethoprim had worse clinical outcomes following empirical treatment with trimethoprim 200 mg twice daily for 3 days than did those with a susceptible isolate. PATIENTS AND METHODS: This was a prospective cohort study of clinical outcome. We enrolled 497 women (>or=18-70 years) presenting to general practitioner surgeries in Norwich and Gloucester with at least two symptoms of acute (<7 days) uncomplicated UTI. Significant bacteriuria was defined as >or=10(4) cfu/mL from a mid-stream urine (MSU). RESULTS: Of enrolled patients 75% (334/448) had significant bacteriuria, and trimethoprim resistance was present in 13.9% (44/317) of isolates. Patients with resistant isolates had a longer median time to symptom resolution (7 versus 4 days, P=0.0002), greater reconsultation to the practice (39% versus 6% in first week, P<0.0001), more subsequent antibiotics (36% versus 4% in first week, P<0.0001) and higher rates of significant bacteriuria at 1 month (42% versus 20% with susceptible isolate, P=0.04). Half of patients reconsulting in the first week had a resistant organism. CONCLUSIONS: Patients with uncomplicated UTI caused by trimethoprim-resistant organisms had significantly worse clinical outcomes than those with trimethoprim-susceptible organisms. Nevertheless, trimethoprim resistance was rarer than predicted from routine laboratory submissions and we calculate that 23 women require microbiological investigation to prevent one reconsultation arising from resistance-based treatment failure. We therefore suggest empirical antibiotic treatment in acute, uncomplicated UTIs. If patients reconsult in the first week, we suggest a change of antibiotic treatment with urine culture and susceptibility testing then done. More generally, laboratory resources should concentrate on resistance surveillance to inform empirical antibiotic choice.

A brief history of testosterone.

PURPOSE: We explore the history of testosterone in the context of medical and scientific developments. MATERIALS AND METHODS: A review of the scientific and historical literature was conducted. RESULTS: The origins and effects of testosterone have been recognized throughout the history of humankind. Hunter performed testicular transplantation experiments in 1767 while studying tissue transplantation techniques, and almost a century later Berthold linked the physiological and behavioral changes of castration to a substance secreted by the testes. Brown-Séquard gave birth to the field of organotherapy in 1889 when he announced that his auto-injection of testicular extracts resulted in rejuvenated physical and mental abilities. Steinach and Niehans expanded upon Brown-Séquard's work with rejuvenation treatments involving vasoligation, tissue grafts and cellular injections. In 1935 David et al isolated the critical ingredient in organotherapeutic treatments, testosterone. CONCLUSIONS: The effects of the powerful hormone testosterone continue to inspire research and controversy 65 years later.

The effect of dehydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profiles, lipid parameters, and health-related quality of life.

Dehydroepiandrosterone (DHEA), an androgenic steroid hormone, exhibits an age-related decline. Perimenopausal women have only approximately 50% of peak DHEA levels. Despite limited scientific data, DHEA has gained recognition as a dietary supplement to reduce the symptoms of aging and improve well-being. This randomized, double-blind placebo-controlled trial examined the effects of 50 mg/day of oral DHEA supplementation, for 3 months, on 60 perimenopausal women with complaints of altered mood and well-being. Changes in the serum endocrine profile of women in the DHEA group were significantly greater than the placebo group, including a 242% [95% confidence interval (CI) +60.1, +423.9] increase in DHEAS, a 94.8% (95% CI +34.2, +155.4) increase in testosterone, and a 13.2% (95% CI -27.88, +0.5) decline in cortisol compared to baseline. Women receiving DHEA had a 10.1% (95% CI -15.0, -5.1) decline in high-density lipoprotein and an 18.1% (95% CI -32.2, -3.9) decline in Lp(a) from baseline, but these declines did not significantly differ from women who received placebo. Women receiving DHEA did not have any improvements significantly greater than placebo in the severity of perimenopausal symptoms, mood, dysphoria, libido, cognition, memory, or well-being. DHEA supplementation significantly effects the endocrine profile, may affect the lipid profile, but does not improve perimenopausal symptoms or well-being compared to placebo.

Evaluating alternative treatments for HIV infection.

Complementary and alternative medicine (CAM) offers views of disease and its treatment that may not compatible with western medicine. In this review of CAM, the authors provide a strategy by which to evaluate CAM in advanced nursing practice. The strategy is shaped by critiques of how to study CAM in light of the relationships that nurses share with their patients. Expert nursing knowledge of HIV-infected patients, in combination with acquired understandings of CAM, offer nurses additional interventions to use in the management of HIV-related symptoms.

A clinician's guide to the premenstrual syndrome.

Many women have menstrual symptoms, but relatively few have severe PMS. PMS is a well-defined premenstrual cluster of predominantly affective symptoms that disrupt a woman's daily functioning. PMS is diagnosed with prospective charting of symptoms and should be differentiated from nondisruptive menstrual symptoms, major affective disorders, and other common medical and gynecologic conditions. Most women with PMS can be helped. The serotonin reuptake inhibitors are becoming the first line of therapy for PMS because they are effective, easily tolerated, and free of major side effects. There is also evidence supporting the role of other antidepressants, anxiolytics, and GnRH agonists in the treatment of PMS. Although increasing control of one's life, promoting a healthy diet, the avoidance of salt and caffeine, vitamin supplementation, and exercise have not been proved as effective treatment for PMS, they should be promoted for their obvious general health benefits. No one treatment fits the heterogeneous PMS population. A trial of medication should be continued for two or three menstrual cycles with appropriate dose adjustments. If relief is not sufficient, other agents or other treatments should be initiated.

Effects of gold salts on experimental periodontitis. I. Histometric evaluation of periodontal destruction.

Systemic administration of gold salts for treatment of arthritis is thought to limit tissue destruction through alteration of inflammatory cell function. The present study ascertained if gold salts could modify the tissue destruction associated with an experimental marginal periodontitis. Therapeutic levels of serum gold salts were established in four squirrel monkeys (experimental) by intramuscular injection of Myochrisine (gold sodium thiomalate 25 mg/ml) at 5 mg/kg/body weight at 4-day intervals for 12 days. Marginal periodontitis was then induced around mandibular bicuspids by tying plaque retentive ligatures at the gingival margins. Periodontitis was induced around corresponding teeth in four control animals which had not received gold salts. Serum levels of gold salts were maintained in experimental animals, and all animals were killed 2 weeks after induction of periodontitis. Progression of periodontitis was evaluated histometrically on step-serial sections, and the results analyzed statistically. Specimens from gold-receiving animals had significantly smaller areas of infiltrated supracrestal connective tissue, and less loss of connective tissue attachment and coronal alveolar bone. Quantitation of total plaque around the ligatures showed no differences; however, there was less plaque located apical to the ligatures in gold-receiving specimens. Although the study design did not permit identification of the relative importance of cellular or microbial factors, it was concluded that administration of systemic gold salts was associated with significantly less periodontal destruction.

Effects of gold salts on experimental periodontitis. II. Cell population characteristics.

A previous study showed that the systemic administration of soluble gold salts (gold sodium thiomalate) resulted in significantly less periodontal destruction after 2 weeks of experimentally induced periodontitis. In order to provide information on the possible mechanisms of action of gold salts in the experimental periodontitis situation, the present study analyzed and compared the characteristics of the inflammatory cell populations in animals receiving gold salts with those present in animals which had not received gold salts. Maxillary gingival biopsy specimens were obtained from the buccal aspect of ligatured teeth after 2 weeks of experimental periodontitis. Cell populations were characterized and enumerated, on 1-micron sections, in an epithelial and superficial connective tissue zone, and a deep connective tissue zone. Significantly fewer inflammatory cells were present in experimental (gold receiving) specimens, and this reduction was due primarily to fewer polymorphonuclear leucocytes (PMNs). No significant reduction occurred in any other inflammatory cell-type. The reduction in number of PMNs in experimental specimens was associated with a decreased number of morphologically altered, degenerating fibroblasts in the connective tissue compared to the PMN-dominated lesion of control specimens. Mechanisms whereby gold salts can reduce chemotaxis and functional capabilities of inflammatory cells are discussed.