The role of adjuvant probiotics to attenuate intestinal inflammatory responses due to cancer treatments.

Chemotherapy and radiotherapy treatment regimens for gastrointestinal, peritoneal and pelvic tumours can disrupt the intestinal microbiome and intestinal epithelia. Such disturbances can provoke symptoms such as diarrhoea, nausea and vomiting. Chemotherapy and radiotherapy induced gastrointestinal toxicity aggravating intestinal microbiome dysbiosis is postulated to adversely alter the intestinal microbiome, with a consequent induced pro-inflammatory effect that disrupts the intestinal microbiome-epithelia-mucosal immunity axis. Although not widely recognised, the intestinal mucosa is the largest and most densely and dynamically populated immune-environment. Cancer treatment adverse effects that affect intestinal and mucosal cells inadvertently target and disrupt resident intestinal macrophages, the cells that marshal immune activity in the intestinal mucosa by shaping pro-inflammatory and anti-inflammatory activities to control and eradicate infectious insults and maintain local homeostasis. Pathobionts (bacteria capable of pathogenic pro-inflammatory activity) and noxious environmental and bacterial antigens use the intestinal epithelia and gap junctions as a point of entry into the systemic circulation. This translocation movement promotes toxic sequelae that obstruct intestinal macrophage functions resulting in uncontrolled local and systemic pro-inflammatory activity, loss of phagocytic function and loss of expression of tight junction proteins. Probiotic bacteria as an adjunctive treatment shows efficacy in ameliorating enteropathies such as mucositis/diarrhoea resulting from chemotherapy or radiotherapy regimens. As such we posit that an important benefit that warrants a further focused research effort is the administration of adjuvant probiotics to help reduce the incidence of febrile neutropenia.

Omega-3 fatty acids: a review of the effects on adiponectin and leptin and potential implications for obesity management.

An increase in adiposity is associated with altered levels of biologically active proteins. These include the hormones adiponectin and leptin. The marked change in circulating concentrations of these hormones in obesity has been associated with the development of insulin resistance and metabolic syndrome. Variations in dietary lipid consumption have also been shown to impact obesity. Specifically, omega-3 fatty acids have been correlated with the prevention of obesity and subsequent development of chronic disease sequalae. This review explores animal and human data relating to the effects of omega-3 fatty acids (marine lipids) on adiponectin and leptin, considering plausible mechanisms and potential implications for obesity management. Current evidence suggests a positive, dose-dependent relationship between omega-3 fatty acid intake and circulating levels of adiponectin. In obese subjects, this may translate into a reduced risk of developing cardiovascular disease, metabolic syndrome and diabetes. In non-obese subjects, omega-3 is observed to decrease circulating levels of leptin; however, omega-3-associated increases in leptin levels have been observed in obese subjects. This may pose benefits in the prevention of weight regain in these subjects following calorie restriction.

A review of the pharmacobiotic regulation of gastrointestinal inflammation by probiotics, commensal bacteria and prebiotics.

The idea that microbes induce disease has steered medical research toward the discovery of antibacterial products for the prevention and treatment of microbial infections. The twentieth century saw increasing dependency on antimicrobials as mainline therapy accentuating the notion that bacterial interactions with humans were to be avoided or desirably controlled. The last two decades, though, have seen a refocusing of thinking and research effort directed towards elucidating the critical inter-relationships between the gut microbiome and its host that control health/wellness or disease. This research has redefined the interactions between gut microbes and vertebrates, now recognizing that the microbial active cohort and its mammalian host have shared co-evolutionary metabolic interactions that span millennia. Microbial interactions in the gastrointestinal tract provide the necessary cues for the development of regulated pro- and anti-inflammatory signals that promotes immunological tolerance, metabolic regulation and other factors which may then control local and extra-intestinal inflammation. Pharmacobiotics, using nutritional and functional food additives to regulate the gut microbiome, will be an exciting growth area of therapeutics, developing alongside an increased scientific understanding of gut-microbiome symbiosis in health and disease.

Mind-body medicine: stress and its impact on overall health and longevity.

The belief that adverse life stressors and the emotional states that can lead to major negative impacts on an individual's body functions and hence health has been held since antiquity. Adverse health outcomes such as coronary heart disease, gastrointestinal distress, and cancer have been linked to unresolved lifestyle stresses that can be expressed as a negative impact on human survival and ultimately a decrease of the human life span. Psychological modulation of immune function is now a well-established phenomenon, with much of the relevant literature published within the last 50 years. Psychoneuroimmunology and psychoneuroendocrinology embrace the scientific evidence of research of the mind with that of endocrinology, neurology and immunology, whereby the brain and body communicate with each other in a multidirectional flow of information that consists of hormones, neurotransmitters/neuropeptides, and cytokines. Advances in mind-body medicine research together with healthy nutrition and lifestyle choices can have a significant impact on health maintenance and disease prevention and hence the prolongation of the human life span.

Can we delay aging? The biology and science of aging.

Long before the fountain of youth, mankind has had an interest in staying young. As we move into the 21st century, that interest has not only continued, but it has become an obsession. While no one can really prevent normal, chronological aging, there are things we can do to slow down "pathological aging." After all, aging is about accelerated inflammation, depletion, and wear and tear. With the marked increase in life expectancy and life span, clinicians need to be aware of the effects of aging on the provision of treatment modalities. Appropriate interventions individualized to the patient can help to "compress morbidity" by shortening the period of functional decline common in old age. Therefore, the "health span" will come closer to matching the life span. Disease and disuse are far more likely explanations for functional decline and the onset of common chronic conditions in older persons than is "true" natural or normal aging. Regardless of your genetic inheritance, you can accelerate aging by lifestyle choices and environmental conditions to which you expose your genes. There are even ways to reverse the problems associated with aging. Getting older does not have to mean growing older. Welcome to the world of preventative gerontology, better known as anti-aging medicine!

An investigation into the acute nootropic effects of Hypericum perforatum L. (St. John's Wort) in healthy human volunteers.

Hypericum perforatum L. (St. John's Wort) is a complex herb that has been used for centuries for its putative medicinal properties, and has current therapeutic relevance as a treatment of mild to moderate depression. Recently, two studies in rodents have suggested that hypericum may also have memory-enhancing effects. It has a complex pharmacology, in that acute administration modulates numerous neurotransmitter systems that have previously been observed to either augment or impair a variety of memory processes in humans. This study aimed to examine whether acute administration of standardized hypericum extract could exert a nootropic effect in normal human subjects. The study employed a double-blind, crossover, repeated-measures design. Twelve healthy young subjects completed the Cognitive Drug Research (CDR) memory battery, following administration of placebo, 900 mg and 1800 mg hypericum (Blackmore's Hyperiforte). The findings suggested that hypericum does not have an acute nootropic effect in healthy humans at these doses. However, there was some evidence for an impairing effect on accuracy of numeric working memory and delayed picture recognition at the higher dose. This observed impairment could be due to a sensitivity of these specific tasks to modulation by neurotransmitters that have been noted to have memory-impairing effects (e.g. y-aminobutyric acid (GABA), serotonin).

Clinical outcomes in terminally ill patients admitted to hospice care: diagnostic and therapeutic interventions.

This study's aim was to determine the impact of medical technologies on patient comfort and survival time, through retrospective review of the clinical course, symptom profile, and illness trajectory in 102 consecutive patients (50 males and 52 females), and of diagnostic and therapeutic interventions delivered to them. The average age of males was 72.3 years and of females 73.1 years. Ninety-four patients were admitted for palliation of symptoms due to malignant disease and eight other patients for non-malignant diseases. The median survival time was 12 days. On admission, higher univariate hazard risks for survival were significantly associated with male gender, metastatic disease, and dyspnea. Higher adjusted Charlson comorbidity scores were associated with significantly decreased survival time, while de novo symptoms and diagnostic interventions were associated with lower univariate risk rates and increased survival times. Palliative therapeutic interventions were not significantly associated with increased patient survival. A multivariate analysis showed that pain, dyspnea, immobility, and adjusted Charlson comorbidity scores were independent risks for shorter patient survival times. Diagnostic interventions were significant for increased patient survival. No requests for euthanasia had been recorded, which may, in part, reflect the significant family support most of these patients had received.

Psychosocial interventions and cancer patients: psychological and immune responses may depend on cancer type.

Psychological and immunological responses of cancer patients to a psychosocial intervention program will be assessed over time. Previously it has been proposed that there are two large divisions in cancer histology (type I and II) and that the psychobiology of patients will vary accordingly.

A preliminary investigation on the acute pharmacodynamic effects of hypericum on cognitive and psychomotor performance.

Research has indicated that the herb St John's Wort (Hypericum perforatum) has comparable efficacy to conventional antidepressants in the treatment of depression. Although clinical studies have demonstrated that hypericum has a superior side-effect profile compared to standard antidepressants, no study has directly compared the cognitive and psychomotor effects of hypericum with those of other antidepressants. The aim of the current study was to examine the acute effects of hypericum on cognitive and psychomotor function, and to compare its effects with those of amitriptyline. Thirteen healthy volunteers received an acute dose of placebo, amitriptyline (25 mg, positive control) or hypericum (900 mg or 1800 mg) in a double-blind, placebo-controlled design. Cognitive and psychomotor tests and subjective measures of sedation were administered before and 1, 2 and 4 hours after drug administration. Amitriptyline impaired performance on a battery of psychological tests, which included critical flicker fusion (CFF), choice reaction time (CRT), digit symbol substitution test (DSST), profile of mood states (POMS) and the line analogue rating scale (LARS), while hypericum had neutral effects on performance in these tests. However, hypericum induced a dose-related impairment on DSST. Current findings suggest that clinical doses of hypericum do not impair attention, sensorimotor function or information processing.

Bacterial infections in terminally ill hospice patients.

Terminally ill patients are very susceptible to infections, which are the result of disease-related processes and/or therapy-induced mechanisms. These patients are already subject to multiple severe symptoms and associated comorbid conditions, with much resultant distress. Infection increases this symptom burden and further reduces quality of life. We have retrospectively investigated the prevalence of infection and clinical course in 102 consecutive patients who died after admission to a tertiary palliative care unit and assessed the site-specific frequency of infection, pathogenic organisms involved, and the pattern of antibiotic agents used. The prevalence of symptoms and comorbid conditions on admission and during the progress phase of care were noted. Median overall survival of the total cohort was 12 days. The median survival of patients with infections was 22 days. Thirty-seven patients (36.3%) were diagnosed with 42 separate infections. The sites of infections were the urinary tract (42.5%), the respiratory tract (22.9%), blood (12.5%), skin and subcutaneous tissues (12.5%), and the eyes (10.0%). There were 20 separate positive cultures isolated from specimens obtained from 13 individual patients. Three isolates were obtained from 1 patient, 2 isolates obtained from 5 patients, and 1 isolate was obtained from each of the 7 remaining patients. Escherichia coli was the most common pathogen isolated. Eleven patients with infections (31.4%) were diagnosed on admission, and antibiotic treatment was commenced within 48 hours of admission in 21 patients (60%). Overall antibiotic response and symptom control of infections was observed to be a minimum of 40%. Psychological distress was common in this group of patients (P = 0.001) as were disabling symptoms on admission, such as pain, immobility, and weakness. Symptoms indicating poor survival, such as severe pain and dyspnea, were not significantly associated with infection. Decreased patient survival in this cohort was not significantly associated with the presence of bacterial infection (P = 0.07), irrespective of whether or not a positive culture isolate was obtained. We conclude that appropriate management of infection resulted in enhanced palliative symptom control.

Single and multiple cholesterol gallstones and the influence of bacteria.

Single and multiple cholesterol gallstones constitute at least 80% of the gallstone population observed at cholecystectomy in Western countries. While supersaturation of bile with cholesterol is necessary for gallstone growth, the kinetic determinant of crystal nucleation is perhaps the critical factor leading to the incidence of gallstones. Nucleation involves aggregation of nidus-forming materials like pigment precipitates and mucus proteins. In combination with cholesterol precipitates and crystal formation, gallstone propagation is enhanced. Bacterial species may augment the process of nucleation and gallstone growth by contributing specific enzyme activities resulting in the formation of insoluble precipitates in bile, or by acting as a nidus upon which the deposition of cholesterol crystals may initiate gallstone formation. The utilization of Raman microscopic techniques permits detailed mapping of the distribution of the gallstone components leading to identification and characterization of the site of nucleation. This, when coupled to molecular genetic tools such as PCR DNA amplification, would permit elucidation of the role of bacteria in vivo gallstone propagation mechanisms.

Gallstones and gall bladder carcinoma.

BACKGROUND: The present study reviewed the occurrence of gall bladder carcinoma in patients who underwent a cholecystectomy for gallstone disease. METHODS: A retrospective study of demographical and clinical information for patients who underwent a cholecystectomy and operative cholangiogram for gallstones predominantly in three major hospitals located in the northern area of Melbourne was carried out. RESULTS: Gall bladder carcinomas were observed in 14 patients (3.2%; 95% confidence interval (CI): 1.8-5.3%) consisting of 11 women and three men of median age 78.5 years (interquartile range: 77-81) from a series of 439 patients with a male-to-female ratio of 1-2. The results of the present study show that primary carcinoma of the gall bladder in this descriptive retrospective cohort was always associated with single or multiple cholesterol gallstones that were impacting on the gall bladder wall. Cholesterol 'solitaire' gallstones were ovoid in shape with diameters > 3 cm along their longest axis, whereas multiple cholesterol gallstones varied in size and number from two or three large stones (1-2 cm), to numerous smaller stones (variable size to 0.5 cm). No patient with gall bladder carcinoma had either brown or black pigment gallstones. CONCLUSION: It is postulated that gall bladder carcinoma may be intimately associated with large or numerous cholesterol gallstones that in the first instance may interfere with the mechanical functioning of the gall bladder. The size as well as the number of gallstones present in the gall bladder may contribute significantly to the promotion of a gallstone filling defect of the gall bladder that may cause chronic mechanical damage to the gall bladder mucosa. The present report supports the hypothesis that gall bladder carcinoma is an age-dependent malignancy, present mostly in women, that may be intimately associated with long-standing benign gallstone disease of the gall bladder.

Psychological morbidity and quality of life in Australian women with early-stage breast cancer: a cross-sectional survey.

OBJECTIVE: To determine the prevalence of psychological morbidity and describe quality of life in women with early-stage breast cancer. DESIGN: Cross-sectional descriptive study (3 months after conservative breast surgery or mastectomy) of patients from nine general hospitals in Melbourne, Victoria, October 1994 to March 1997. PARTICIPANTS: 303 women with early-stage breast cancer entering a randomised trial of adjuvant psychological group therapy; mean age, 46 years (SD, 8). MAIN OUTCOME MEASURES: Diagnostic and Statistical Manual of Mental Health (DSM)-IV psychiatric diagnoses generated by the Monash Interview for Liaison Psychiatry; quality-of-life data based on the the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (QLQ)-C30 (core) and QLQ-BR23 (breast module) instruments. RESULTS: 45% of the women (135/303) had a psychiatric disorder; 42% (127) of the sample had depression or anxiety, or both; there was minor depression in 82 (27.1%), an anxiety disorder in 26 (8.6%), major depression in 29 (9.6%) and a phobic disorder in 21 (6.9%). 20% of women (61) had more than one disorder. On quality-of-life measures nearly one-third of the women felt less attractive and most had lost interest in sexual activity. There was substantial distress about hair loss. Symptoms of lymphoedema were described by 13 women (4.3%). Breast conservation surgery was associated with a better body image (P<0.01). CONCLUSION: Women recently diagnosed with early-stage breast cancer have high rates of psychiatric and psychological disturbance. Quality of life is substantially affected. Clinicians should actively explore their patients' psychological adjustment to enable early recognition and treatment of these disorders.

Oral and pharyngeal cancer, diet, smoking, alcohol, and serum vitamin A and beta-carotene levels: a case-control study in men.

A case-control study was conducted in Melbourne, Australia. Forty-one men with histologically confirmed squamous cell oral or pharyngeal cancer were compared with 398 male community controls. A statistically significant increase in risk was found for alcohol (ethanol) consumption and for smoking, and there was a synergistic effect for these two exposures. Statistically significant protection was noted with increasing intake of dietary vitamin C, dietary beta-carotene, fruit, vegetables, and dietary fiber. The mean serum levels of beta-carotene and vitamin A were statistically significantly lower when the cases were compared with another set of 88 male controls of a similar age who were hospitalized for minor surgical operations. This study confirms a causal effect of smoking and alcohol and a protective role for a high dietary intake of fruit, vegetables, cereals, and, particularly, beta-carotene- and vitamin C-containing foods.

Smoking and colorectal cancer risk: data from the Melbourne Colorectal Cancer Study and brief review of literature.

Lifetime smoking data were obtained from 715 colorectal cancer cases and 727 age/sex matched community controls as one part of a large, comprehensive, population-based study of colorectal cancer aetiology and survival in Melbourne, Australia, The Melbourne Colorectal Cancer Study. Statistically significant associations were found for those males smoking handrolled cigarettes and for cigar-/pipe-smoking males with colon cancer. Review of 18 previous case control studies of colorectal cancer showed an elevated risk for cigar-smoking black males in one study, a statistically non-significant increased risk for current smokers in one of 3 cohort studies and a statistically significant elevation of risk for smokers in 2 of 3 studies of adenomatous large-bowel polyps. Although at present there is insufficient evidence to link smoking with large-bowel cancer, the possibility that ingested tobacco is in some way carcinogenic for the colorectal mucosa may be worth further study.