A randomised double-blind placebo-controlled pilot trial of a combined extract of sage, rosemary and melissa, traditional herbal medicines, on the enhancement of memory in normal healthy subjects, including influence of age.

OBJECTIVE: To evaluate for the first time the effects of a combination of sage, rosemary and melissa (Salvia officinalis L., Rosmarinus officinalis L. and Melissa officinalis L.; SRM), traditional European medicines, on verbal recall in normal healthy subjects. To devise a suitable study design for assessing the clinical efficacy of traditional herbal medicines for memory and brain function. METHODS: Forty-four normal healthy subjects (mean age 61 ± 9.26y SD; m/f 6/38) participated in this study. A double-blind, randomised, placebo-controlled pilot study was performed with subjects randomised into an active and placebo group. The study consisted of a single 2-week term ethanol extract of SRM that was chemically-characterised using high resolution LC-UV-MS/MS analysis. Immediate and delayed word recall were used to assess memory after taking SRM or placebo (ethanol extract of Myrrhis odorata (L.) Scop.). In addition analysis was performed with subjects divided into younger and older subgroups (≤ 62 years mean age n = 26: SRM n = 10, Placebo n = 16; ≥ 63 years n = 19: SRM n = 13, Placebo n = 6). RESULTS: Overall there were no significant differences between treatment and placebo change from baseline for immediate or delayed word recall. However subgroup analysis showed significant improvements to delayed word recall in the under 63 year age group (p < 0.0123) with Cohen's effect size d = 0.92. No adverse effects were observed. CONCLUSION: This pilot study indicates that an oral preparation of SRM at the selected dose and for the period of administration is more effective than a placebo in supported verbal episodic memory in healthy subjects under 63 years of age. Short- and long- term supplementation with SRM extract merits more robust investigation as an adjunctive treatment for patients with Alzheimer's disease and in the general ageing population. The study design proved a simple cost effective trial protocol to test the efficacy of herbal medicines on verbal episodic memory, with future studies including broader cognitive assessment.

Application of the general health status questionnaire SF36 to patients with gastrointestinal dysfunction: initial validation and validation as a measure of change.

OBJECTIVE: To determine whether the Short Form (SF36) Health Status Survey is a valid measure of health status and health change for patients with irritable bowel syndrome (IBS). METHODS: The SF36 was self-administered by 116 patients with IBS at the commencement and end of a controlled clinical trial. Patients were recruited through two Sydney teaching hospitals and through private gastroenterologists during 1997 and treated with Chinese herbal medicine. RESULTS: The SF36 health concepts demonstrated internal consistency, construct validity and concurrent validity when applied to patients with significant bowel dysfunction. Patient scores on two health scales of the SF36 (bodily pain, general health) correlated significantly with the bowel symptom scores recorded by patients and gastroenterologists at the beginning and end of the trial period. Actively treated patients significantly improved their scores in four out of eight of the health scales of the SF36 and reported overall improvement compared with inactively treated patients. CONCLUSIONS: The SF36 is a valid measure of general health status in IBS patients, is sensitive to the presence of IBS, and is adequately sensitive to gastrointestinal change in IBS patients. IMPLICATIONS: While the SF36 general health measure is used by the Australian Bureau of Statistics and widely overseas, until recently no data have been available on the sensitivity of the SF36 to gastrointestinal dysfunction or numerous other disorders. The SF36 is not only sensitive to the presence of IBS, it also provides a useful adjunct to current methods of evaluating treatment outcomes for IBS, and potentially other disorders.

Treatment of irritable bowel syndrome with Chinese herbal medicine: a randomized controlled trial.

CONTEXT: Irritable bowel syndrome (IBS) is a common functional bowel disorder for which there is no reliable medical treatment. OBJECTIVE: To determine whether Chinese herbal medicine (CHM) is of any benefit in the treatment of IBS. DESIGN: Randomized, double-blind, placebo-controlled trial conducted during 1996 through 1997. SETTING: Patients were recruited through 2 teaching hospitals and 5 private practices of gastroenterologists, and received CHM in 3 Chinese herbal clinics. PATIENTS: A total of 116 patients who fulfilled the Rome criteria, an established standard for diagnosis of IBS. INTERVENTION: Patients were randomly allocated to 1 of 3 treatment groups: individualized Chinese herbal formulations (n = 38), a standard Chinese herbal formulation (n = 43), or placebo (n = 35). Patients received 5 capsules 3 times daily for 16 weeks and were evaluated regularly by a traditional Chinese herbalist and by a gastroenterologist. Patients, gastroenterologists, and herbalists were all blinded to treatment group. MAIN OUTCOME MEASURES: Change in total bowel symptom scale scores and global improvement assessed by patients and gastroenterologists and change in the degree of interference in life caused by IBS symptoms assessed by patients. RESULTS: Compared with patients in the placebo group, patients in the active treatment groups (standard and individualized CHM) had significant improvement in bowel symptom scores as rated by patients (P=.03) and by gastroenterologists (P=.001), and significant global improvement as rated by patients (P=.007) and by gastroenterologists (P=.002). Patients reported that treatment significantly reduced the degree of interference with life caused by IBS symptoms (P=.03). Chinese herbal formulations individually tailored to the patient proved no more effective than standard CHM treatment. On follow-up 14 weeks after completion of treatment, only the individualized CHM treatment group maintained improvement. CONCLUSION: Chinese herbal formulations appear to offer improvement in symptoms for some patients with IBS.

In vivo release of interleukin-1 beta into hypothalamic extracellular fluid in rats: effects of repeated sampling.

Interleukin-1 beta (Il-1 beta) concentrations in extracellular fluid (ECF) withdrawn at 10-min intervals through a push-pull cannula (PPC) located in the hypothalamus were studied in freely behaving male rats for 1 h at 24 and 72 h and again at 7 days after PPC implantation. Il-1 beta concentrations in ECF were similar in the latter. However, when ECF was sampled at 3 h and again 7 days after PPC implantation, Il-1 beta concentrations were greatly elevated at 7 days when compared to all other intervals. These results demonstrate how the relationships between Il-1 beta measured in ECF and the conditions of measurement appear to be integral parts of a whole intracerebral system: cytokine concentrations appear to be inextricably bound to intrahypothalamic conditions created by the sampling device presence and frequency of use.

Interleukin-1 beta stimulates adrenocorticotropin and corticosterone release in 10-day-old rat pups.

Interleukin-1 (IL-1) is a cytokine secreted in response to immunological challenge which has effects in many physiological systems in adult models. Among the central nervous system effects of IL-1 are its ability to alter sleep patterns, body temperature, and certain neuroendocrine parameters including the release of ACTH and corticosterone (B) in vivo. This study investigated the ability of IL-1 to induce ACTH and B release in 10-day-old rats. This age was chosen due to a well documented phenomenon, the stress hyporesponsive period (SHRP), in which rodents display a blunted pituitary-adrenal response to stressors during the first 2 postnatal weeks (postnatal days 3-14). Administration of IL-1 to rat pups during the SHRP resulted in robust ACTH and B increases. Data are discussed in terms of the site of action and ontogeny of negative feedback mechanisms in the hypothalamic-pituitary-adrenal axis.

Effects of exercise on immune functions of undernourished mice.

Regular moderate exercise may modulate the response to a stressor and thus improve immune functions in conditions commonly associated with immunodepression and elevated levels of stress hormones. For example, anorexia nervosa patients, many of whom engage in regular aerobic exercise, generally have normal immune function and viral disease resistance in spite of their severe undernutrition. To test the hypothesis that exercise can prevent undernutrition-induced immunodepression, mice were fed a nutritionally complete, semi-purified diet, either ad libitum or in restricted quantities to induce 25% loss of initial weight over 3 weeks. Half the animals from each dietary group were run on a treadmill for 30 min/day, 5 days/week. Exercise had no effect on several measures of nutritional status. Spleen weight and blastogenic response to lipopolysaccharide were significantly increased by exercise in undernourished mice. In vivo antibody response to sheep red blood cells, and in vitro splenic responses to concanavalin A and phytohemagglutin were not significantly affected by exercise. Serum corticosterone level was increased by food restriction and significantly decreased by exercise in the undernourished mice. Within a treatment group there were no significant correlations between serum corticosterone level and any immune system measure. Hypothalamic concentration of uric acid was increased in food restriction groups and concentration of norepinephrine was increased in exercise groups. The results suggest that regular exercise may help prevent undernutrition-induced immunodepression, possibly through modulation of the stress response.

Adaptation of methicillin-resistant Staphylococcus aureus during antibiotic therapy.

Colonization of a patient by methicillin-resistant Staphylococcus aureus (MRSA) of a single phage-type for over four years is described. During this period we observed the appearance and disappearance of resistance to erythromycin, clindamycin, gentamicin, kanamycin, tobramycin, neomycin and mupirocin. We also saw stepwise increases in methicillin resistance and reversible changes in physical appearance and the colonizer pathogen role. Correlation of clinical observations, details of antibiotic therapy and laboratory studies demonstrated that adaptation of MRSA during antibiotic therapy favoured MRSA establishment and predominance.