Effects of a standardised extract of Trifolium pratense (Promensil) at a dosage of 80mg in the treatment of menopausal hot flushes: A systematic review and meta-analysis.

OBJECTIVE: To critically assess the evidence for a specific standardised extract of Trifolium pratense isoflavones (Promensil) at a dosage of 80mg/day in the treatment of menopausal hot flushes. DATA SOURCES: Systematic literature searches were performed in Medline, Scopus, CINAHL Plus, Cochrane, AMED and InforRMIT and citations obtained from 1996 to March 2016. Reference lists were checked; corresponding authors contacted and the grey literature searched for additional publications. REVIEW METHODS: Studies were selected according to predefined inclusion and exclusion criteria. All randomised clinical trials of a specific standardised extract of Trifolium pratense isoflavones (Promensil) used as a mono-component at 80mg/day and measuring vasomotor symptoms were included. The data extraction and quality assessment were performed independently by one reviewer and validated by a second with any disagreements being settled by discussion. Weighted mean differences and 95% confidence intervals were calculated for continuous data using the fixed-effects model. RESULTS: Twenty potentially relevant papers were identified, with only five studies meeting the inclusion criteria. The meta-analysis demonstrated a statistical and clinically relevant reduction in hot flush frequency in the active treatment group compared to placebo. Weighted mean difference 3.63 hot flushes per day: [95% CI 2.70-4.56]; p˂0.00001). Due to a lack of homogeneity a priori defined sub-group analyses were performed demonstrating a substantive difference between cross-over and parallel-arm clinical trial designs. CONCLUSION: There is evidence for a statistical and clinically significant benefit for using a specific standardised extract of red clover isoflavones (Promensil) at 80mg/day for treating hot flushes in menopausal women across the 3 studies included in the meta-analysis. The preparation was safe over the short-term duration of the studies (3 months).

The effects of oral garlic on vaginal candida colony counts: a randomised placebo controlled double-blind trial.

OBJECTIVE: Garlic is effective against Candida species in vitro, and along with other alternative therapies, is used by women with vulvovaginal candidiasis. The objective of this study was to ascertain whether oral garlic reduced vaginal candida counts during the second half of the menstrual cycle in asymptomatic women colonised with Candida species. DESIGN: A simple randomised double-blinded controlled trial. SETTING: Melbourne, Australia. SAMPLE: Sixty-three asymptomatic women who were culture-positive for Candida species at screening. METHODS: Participants were randomised to three garlic tablets or placebo orally, twice daily, for 14 days. MAIN OUTCOME MEASURES: The primary outcome was the proportion of women with colony counts of candida >100 colony-forming units per ml in any given day during the last 7 days before menstruation, defined as a 'case'. Secondary outcomes included the mean quantitative colony counts of candida over 14 days prior to menses. RESULTS: There was no evidence of a difference between the proportion of cases in the garlic and placebo groups (76 versus 90%; relative risk, RR 0.85; 95% confidence interval, 95% CI 0.67-1.08), in the mean colony counts in both groups (ratio of geometric means of candidal colony counts 0.63; 95% CI 0.39-10.03; P = 0.74), or difference in the number of women reporting abnormal vaginal symptoms during the 2 weeks before menstruation (RR 1.03; 95% CI 0.67-1.58; P = 0.91). The garlic group reported more adverse effects (83% compared 43% in the placebo group; difference in proportions 39%; 95% CI 17-%; P < 0.01). CONCLUSIONS: This study provided data for sample size calculations in future studies on the antifungal effect of garlic, but provided no evidence to inform clinical practice regarding the use of garlic in vaginal candidiasis. Further studies might investigate longer courses or topical formulations.

The value of the Australian nutrition screening initiative for older australians--results from a national survey.

BACKGROUND: This national investigation of older Australians was conducted to explore the relationship between their health, lifestyle, use of dietary supplements and nutritional risk. OBJECTIVE: The objective of this study was to examine the extent of poor health status and nutritional risk among Australians aged 65 years and over, as determined by the Australian Nutrition Screening Initiative. DESIGN: The 12 statements that comprise the Australian Nutrition Screening Initiative (ANSI) were incorporated in a comprehensive, self-administered national postal survey designed to elicit information on the health and lifestyle practices of older Australians. In 2001, data were obtained from 1,263 individuals (641 males, 622 females) aged between 65 and 98 years, randomly chosen from the 2000 Australian Electoral roll. RESULTS: According to the ANSI, 59% (n=747) of the sample was at risk of poor nutritional status as well as poor health status. The most frequently occurring risk factors were; taking 3 or more different prescription or over-the-counter drugs each day (44%), having an illness that led to changes to the kind and/or amount of food consumed (34%), eating alone most of the time (28%), not eating dairy products most days (18%), and consuming 3 or more alcoholic beverages each day (18%). Gender differences were observed for several ANSI statements. CONCLUSION: These results suggest that because the ANSI may exaggerate the true extent of nutritional risk among community living older individuals it is of limited value as a screening tool per se. The future of the ANSI should be dependent on verifying its reliability as a public health measure.

The effect of St John's wort extracts on CYP3A: a systematic review of prospective clinical trials.

AIM: The aim of this systematic review was to assess the quality and outcomes of clinical trials investigating the effect of St John's wort extracts on the metabolism of drugs by CYP3A. METHODS: Prospective clinical trials assessing the effect of St John's wort (SJW) extracts on metabolism by CYP3A were identified through computer-based searches (from their inception to May 2005) of Medline, Cinahl, PsycINFO, AMED, Current Contents and Embase, hand-searches of bibliographies of relevant papers and consultation with manufacturers and researchers in the field. Two reviewers selected trials for inclusion, independently extracted data and recorded details on study design. RESULTS: Thirty-one studies met the eligibility criteria. More than two-thirds of the studies employed a before-and-after design, less than one-third of the studies used a crossover design, and only three studies were double-blind and placebo controlled. In 12 studies the SJW extract had been assayed, and 14 studies stated the specific SJW extract used. Results from 26 studies, including all of the 19 studies that used high-dose hyperforin extracts (>10 mg day(-1)), had outcomes consistent with CYP3A induction. The three studies using low-dose hyperforin extracts (<4 mg day(-1)) demonstrated no significant effect on CYP3A. CONCLUSION: There is reasonable evidence to suggest that high-dose hyperforin SJW extracts induce CYP3A. More studies are required to determine whether decreased CYP3A induction occurs after low-dose hyperforin extracts. Future studies should adopt study designs with a control phase or control group, identify the specific SJW extract employed and provide quantitative analyses of key constituents.

Naturopathic and Western herbal medicine practice in Australia-a workforce survey.

BACKGROUND: Despite substantial growth in the use of complementary medicine, no comprehensive national study has been undertaken of the naturopathic and Western herbal medicine component of the healthcare workforce in Australia. This study aimed to examine the nature of these practices and this currently unregulated workforce in Australia. METHODS: A comprehensive survey questionnaire was developed in consultation with the profession and distributed nationally to all members of the naturopathic and Western herbal medicine workforce. RESULTS: The practices of herbal medicine and naturopathy make up a sizeable component of the Australian healthcare sector, with approximately 1.9 million consultations annually and an estimated turnover of $AUD 85 million in consultations (excluding the cost of medicines). A large proportion of patients are referred to practitioners by word of mouth. Up to one third of practitioners work in multidisciplinary clinics with other registered sectors of the healthcare community. The number of adverse events associated with herbal medicines, nutritional substances and homoeopathic medicines recorded in Australia is substantial and the types of events reported are not trivial. Data suggest that practitioners will experience one adverse event every 11 months of full-time practice, with 2.3 adverse events for every 1000 consultations (excluding mild gastrointestinal effects). CONCLUSION: These data confirm the considerable degree of utilisation of naturopathic and Western herbal medicine practitioners by the Australian public. However, there is a need to examine whether statutory regulation of practitioners of naturopathy and Western herbal medicine is required to better protect the public.

The effects of homeopathic Argentum nitricum on test anxiety.

OBJECTIVES: (1) To replicate a study of the efficacy of Argentum nitricum 12X in the reduction of test anxiety as demonstrated previously. (2) To investigate the correlation between individuals identified to match the A. nitricum profile and the reduction of test anxiety. To compare traditionally prepared homeopathic A. nitricum 12X with radionically-prepared A. nitricum 12X and placebo. DESIGN: A double blind, placebo-controlled, randomised clinical trial with three arms. SETTING: The study was conducted at Southern Cross University, Lismore, Australia. SUBJECTS: Sixty-two test anxious university students. INTERVENTIONS: Subjects were randomised to one of three groups: traditionally prepared homeopathic A. nitricum 12X, radionically-prepared A. nitricum 12X, or placebo. After screening, each group received treatment twice a day for 4 days after which they were re-tested. OUTCOME MEASURES: Primary: The Revised Test Anxiety Scale. Secondary: The Test Anxiety Scale; 36-item A. nitricum questionnaire. RESULTS: The results of this study did not replicate the Stanton study. No correlation between the reduction of test anxiety and the A. nitricum profile was demonstrated. No significant differences between treatments were demonstrated. CONCLUSION: This study demonstrated that homeopathic A. nitricum 12X does not reduce test anxiety in a general population of university students.

Risks associated with the practice of traditional Chinese medicine: an Australian study.

OBJECTIVE: To investigate the nature and frequency of adverse events that occur as a result of the practice of traditional Chinese medicine (acupuncture and Chinese herbal medicine) in Australia. METHODS: Data on adverse events were obtained as part of a comprehensive survey of all occupational health groups, government-registered and unregistered, who practiced traditional Chinese medicine or 1 of its main modalities. RESULTS: Practitioners reported numerous adverse events arising from the application of acupuncture (including fainting, nausea and vomiting, and increased pain), or the consumption of Chinese herbal medicines (including direct toxic effects and allergic reactions). Practitioners experienced an average of 1 adverse event every 8 to 9 months of full-time practice or 1 adverse event for every 633 consultations. The mean adverse event rate of nonmedical practitioners was less than half the mean adverse event rate of medical practitioners. CONCLUSIONS: The practices of acupuncture and Chinese herbal medicine are not risk-free and fatalities have occurred. Variation in adverse event rates between medical and nonmedical practitioners may reflect differences in relevant education or different reporting behaviors. These data represent the first step in the evaluation of adverse event rates in traditional Chinese medicine. Arch Fam Med. 2000;9:1071-1078

Malignant ependymomas in a patient with Turcot's syndrome: case report and management guidelines.

BACKGROUND: Turcot's Syndrome is the association of multiple adenomatous polyps of the colon with a primary tumor of the central nervous system. We present the first reported case of Turcot's Syndrome in a patient with malignant ependymomas. Recent advances in the elucidation of the genetic basis for the hereditary forms of colon cancer have provided a clearer understanding of the etiology of Turcot's Syndrome. This new information is relevant to the neurosurgical community and provides updated guidelines in the diagnosis and management of patients with this complex disease process. RESULTS: Turcot's Syndrome is related to two distinct genetic errors. The first involves a germ-line mutation in the adenomatous polyposis coli (APC) gene, which is postulated to act as a tumor suppressor gene. The second is a germ-line defect in one of a group of genes responsible for DNA nucleotide mismatch repair. CONCLUSION: The elucidation of the gene defects responsible for the hereditary forms of colon cancer has provided a clearer understanding of the molecular basis of Turcot's Syndrome. Patients with hereditary forms of colon cancer and neurologic symptoms require immediate and thorough investigation because of their significantly increased risk of developing CNS tumors. Previously healthy patients diagnosed with a CNS tumor with a family history of adenomatous polyposis coli should undergo screening and surveillance colonoscopy as the CNS lesion may precede colonic symptoms. CNS screening guidelines for asymptomatic patients with adenomatous polyposis coli requires further risk analysis studies. All patients diagnosed with Turcot's Syndrome should be tested for the gene defect, including the CNS tumor tissue to provide further data on the genetic relationship between Turcot's Syndrome and the hereditary forms of colon cancer.

Safety issues in herbal medicine: implications for the health professions.

The use of herbal medicines in Australia is widespread. A number of factors make assessment of adverse effects associated with these products more complex than for pharmaceuticals. Problems have resulted from contamination with heavy metals and adulteration with prescription drugs in overseas herbal products. A classification is proposed for adverse effects associated with herbal medicines, and medical practitioners are encouraged to include use of these preparations in a patient's drug history and in reports of suspected adverse drug reactions. It may be necessary to develop a separate database to promote adverse drug reaction reporting for herbal medicine and the wider field of complementary and alternative medicine.

Subfreezing volumetric behavior and stochastic modeling of intracellular ice formation in Drosophila melanogaster embryos.

Cryomicroscopic observations were made of the volumetric behavior and kinetics of intracellular ice formation (IIF) in Drosophila melanogaster embryos in a modified cell culture medium (BD.20) or BD.20 + 2 M ethylene glycol. After rapid cooling to a given temperature, transient volumetric contraction of the embryos during the isothermal period was quantified by computerized video image analysis. Fitting these data to the numerical solution of the volume flux equation yielded estimates of the hydraulic permeability coefficient (Lp) for individual embryos at various subfreezing temperatures. Lp approximately followed an Arrhenius relation between -2 and -9 degrees C, with a value of 0.168 microns/(min-atm) extrapolated to 0 degrees C and an apparent activation energy delta E of 38.9 kcal/mol. IIF during an isothermal period occurred at random times whose characteristic temperature range and kinetics were affected by the presence of ethylene glycol. A stochastic process model developed to fit these data indicated the influence of both time-dependent and instantaneous components of IIF, presumed to be the result of seeding and heterogeneous nucleation, respectively. The presence of 2 M ethylene glycol depressed the characteristic temperature of instantaneous IIF by about 12 degrees C and reduced the rate constant for time-dependent IIF. Comparison with observed incidences of IIF yielded an estimate of the supercooling tolerance of 3 to 5 degrees C.

Cryopreservation of Drosophila melanogaster embryos.

There is an urgent need to preserve the ever-increasing number (greater than 30,000) of different genetic strains of D. melanogaster that are maintained in national and international stock centres and in the laboratories of individual investigators. In all cases, the stocks are maintained as adult populations and require transfer to fresh medium every two to four weeks. This is not only costly in terms of materials, labour and space, but unique strains are vulnerable to accidental loss, contamination, and changes in genotype that can occur during continuous culture through mutation, genetic drift or selection. Although cryopreservation of Drosophila germ-plasm would be an enormous advantage, many attempts using conventional procedures have been unsuccessful. D. melanogaster embryos are refractory to conventional cryopreservation procedures because of the contravening conditions required to minimize mortality resulting from both intracellular ice formation and chilling injury at subzero temperatures. To overcome these obstacles, we have developed a vitrification procedure that precludes intracellular ice formation so that the embryos can be cooled and warmed at ultra-rapid rates to minimize chilling injury, and have recovered viable embryos following storage in liquid nitrogen. In a series of 53 experiments, a total of 3,711 larvae emerged from 17,280 eggs that were cooled in liquid nitrogen (18.4 +/- 8.8%). Further, using a subset from this population, approximately 3% of the surviving larvae (24/800) developed into adults. These adults were fertile and produced an F1 generation.

A two-step method for permeabilization of Drosophila eggs.

As a first step in developing a procedure for the cryopreservation of Drosophila melanogaster embryos, we have established a method for permeabilization of the eggcase and have initiated studies of the hydraulic conductivity of permeabilized embryos and the permeation of selected cryoprotective agents. The eggcase of D. melanogaster embryos has a wax layer that precludes any flux of water. A two-step procedure employing organic solvents was developed to effect removal of the wax layer with minimal deleterious effects on the embryos. Dechorionated embryos (Oregon-R strain P2, 12 to 13 hr old) were rinsed sequentially in isopropanol and hexane. After removal of solvent, embryos were held in a modified cell culture medium for further manipulation. This procedure routinely yielded 80 to 95% of the eggs permeabilized (as determined by osmotic contraction in 1 M sucrose) and 75 to 90% survival (incidence of hatching). Hydraulic conductivity of permeabilized embryos and permeation of cryoprotectants were determined using a microdiffusion chamber and computerized video microscopy. Regression analysis of the volumetric data from individual embryos yielded the Boyle-van't Hoff function FVeq = 0.124 (osm-1) + 0.541 with the standard deviations of slope and intercept (Vb) being 0.010 and 0.040, respectively. Permeabilized embryos exhibited ideal osmotic behavior over the range of 0.265 to 2.00 osm. The mean hydraulic conductivity coefficient (Lp) was 0.722 +/- 0.366 micron/(min.atm) at 20 degrees C, based on observations of contraction following a step change in concentration of Ringer's solution.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of intracellular ice formation in Drosophila melanogaster embryos.

Cryomicroscopy and differential scanning calorimetry (DSC) were used to characterize the incidence of intracellular ice formation (IIF) in 12- to 13-hr-old embryos of Drosophila melanogaster (Oregon-R strain P2) as influenced by the state of the eggcase (untreated, dechorionated, or permeabilized), the composition of the suspending medium (with and without cryoprotectants), and the cooling rate. Untreated eggs underwent IIF over a very narrow temperature range when cooled at 4 or 16 degrees C/min with a median temperature of intracellular ice formation (TIIF50) of -28 degrees C. The freezable water volume of untreated eggs was approximately 5.4 nl as determined by DSC. IIF in dechorionated eggs occurred over a much broader temperature range (-13 to -31 degrees C), but the incidence of IIF increased sharply below -24 degrees C, and the cumulative incidence of IIF at -24 degrees C decreased with cooling rate. In permeabilized eggs without cryoprotectants (CPAs), IIF occurred at much warmer temperatures and over a much wider temperature range than in untreated eggs, and the TIIF50 was cooling rate dependent. At low cooling rates (1 to 2 degrees C/min), TIIF50 increased with cooling rate; at intermediate cooling rates (2 to 16 degrees C/min), TIIF50 decreased with cooling rate. The total incidence of IIF in permeabilized eggs was 54% at 1 degree C/min, and volumetric contraction almost always occurred during cooling. Decreasing the cooling rate to 0.5 degree C/min reduced the incidence of IIF to 43%. At a cooling rate of 4 degrees C/min, ethylene glycol reduced the TIIF50 by about 12 degrees C for each unit increase in molarity of CPA (up to 2.0 M) in the suspending medium. The TIIF50 was cooling rate dependent when embryos were preequilibrated with 1.0 M propylene glycol or ethylene glycol, but was not so in 1.0 M DMSO. For embryos equilibrated in 1.5 M ethylene glycol and then held at -5 degrees C for 1 min before further cooling at 1 degree C/min, the incidence of IIF was decreased to 31%. Increasing the duration of the isothermal hold to 10 min reduced the incidence of IIF to 22% and reduced the volume of freezable water in embryos when intracellular ice formation occurred. If the isothermal hold temperature was -7.5 or -10 degrees C, a 10- to 30-min holding time was required to achieve a comparable reduction in the incidence of IIF.

The fatty acid content and drug binding characteristics of commercial albumin preparations.

The fatty acid contents of thirteen commercial preparations of human albumin were found to be in the range 0.03 to 9 mol of fatty acid/mol albumin. Marked differences were found between the preparations in the binding of the fluorescent probes, 5-dimethylamino-naphthalene-1-sulfonamide (DNSA) and dansylsarcosine. The displacement of these probes by ibuprofen and phenylbutazone also showed marked differences between preparations. The differences between the commercial albumin samples correlated well with their fatty acid contents and were abolished by treatment with charcoal. They were similar to the changes observed when oleic acid was added to fatty acid free albumin. The source and fatty acid content of commercial albumin preparations should be considered when comparing studies of the binding of drugs to human albumin.