Predictors of urinary tract infection after menopause: a prospective study.
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Biomedical subjects
Publications and source records attributed to Gregor Reid.
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OBJECTIVE: Gardnerella vaginalis has long been the most common pathogen associated with bacterial vaginosis (BV). We aimed to test our hypothesis that symptoms and signs of BV do not necessarily indicate colonization by this organism, and often will not respond to standard metronidazole or clindamycin treatment. METHODS: Using a relatively new molecular tool, PCR denaturing gradient gel electrophoresis (DGGE), the vaginal microflora of a woman with recalcitrant signs and symptoms of BV was investigated over a 6-week timeframe. RESULTS: The vagina was colonized by pathogenic enterobacteriaceae, staphylococci and Candida albicans. The detection of the yeast by PCR-DGGE is particularly novel and enhances the ability of this tool to examine the true nature of the vaginal microflora. The patient had not responded to antifungal treatment, antibiotic therapy targeted at anaerobic Gram-negative pathogens such as Gardnerella, nor daily oral probiotic intake of Lactobacillus rhamnosus GG. The failure to find the GG strain in the vagina indicated it did not reach the site, and the low counts of lactobacilli demonstrated that therapy with this probiotic did not appear to influence the vaginal flora. CONCLUSIONS: BV is not well understood in terms of its causative organisms, and further studies appear warranted using non-culture, molecular methods. Only when the identities of infecting organisms are confirmed can effective therapy be devized. Such therapy may include the use of probiotic lactobacilli, but only using strains which confer a benefit on the vagina of pre- and postmenopausal women.
Every minute of every day more and more children die of diarrheal diseases and women, and girls become infected by HIV. An estimated 7,000 women become infected each day. While many valiant efforts are being made to address these issues, until now they have proved to be markedly ineffective. The notion that lactic acid bacteria, formulated into food or dietary supplements, could have a role to play in slowing the morbidity and mortality associated with HIV/AIDS and gastroenteritis, is built upon sound clinical findings and scientific investigations, yet no international efforts have been placed in this approach, to date. We hereby summarize the reasons why such efforts should be made, provide an example of one model being set up in sub-Saharan Africa, and challenge the international community to consider the potential benefits of probiotics, especially for communities not reached by governmental and nongovernmental agencies.
Probiotics, defined as "Live microorganisms which when administered in adequate amounts confer a health benefit on the host" have many attributes including the lack of adverse side effects associated with their use. While probiotics have proven benefits, the optimism associated with their use is counterbalanced by the fact that many so-called "probiotic" products are unreliable in content and unproven clinically. Therefore much remains to be done to gain the acceptance of the broader medical community. Recognition of the obvious product inequality and the lack of any regulatory guidelines lead to the development of Operating Standards in 2002 (FAO/WHO), that would ensure product safety, reliability and a level playing field for all companies producing probiotic products. The guidelines constitute a set of parameters required for a product/strain to be termed "probiotic" and also the clinically relevant steps to be followed to move probiotics closer to being embraced by the medical community. These include i) implementation of Guidelines for use of probiotics; ii) phase I, II and III clinical trials to prove health benefits that are as good as or better than standard prevention or treatments for a particular condition or disease; iii) Good Manufacturing Practice and production of high quality products; iv) studies to identify mechanism of action in vivo; v) informative/ precise labelling; vi) development of probiotic organisms that can carry vaccines to hosts and/or anti- viral probiotics; vii) expansion of proven strains to benefit the oral cavity, nasopharynx, respiratory tract, stomach, vagina, bladder and skin as well as for cancer, allergies and recovery from surgery/ injury.
On August 29-31, 2004, 84 academic and industry scientists from 16 countries gathered in Copper Mountain, Colorado USA to discuss certain issues at the forefront of the science of probiotics and prebiotics. The format for this invitation only meeting included six featured lectures: engineering human vaginal lactobacilli to express HIV-inhibitory molecules (Peter Lee, Stanford University), programming the gut for health (Thaddeus Stappenbeck, Washington University School of Medicine), immune modulation by intestinal helminthes (Joel Weinstock, University of Iowa Hospitals and Clinics), hygiene as a cause of autoimmune disorders (G. A. Rook, University College London), prebiotics and bone health (Connie Weaver, Purdue University) and prebiotics and colorectal cancer risk (Ian Rowland, Northern Ireland Centre for Food and Health). In addition, all participants were included in one of eight discussion groups on the topics of engineered probiotics, host-commensal bacteria communication, 'omics' technologies, hygiene and immune regulation, biomarkers for healthy people, prebiotic and probiotic applications to companion animals, development of a probiotic dossier, and physiological relevance of prebiotic activity. Brief conclusions from these discussion groups are summarized in this paper.
OBJECTIVES: A study was conducted to use new molecular technologies to identify the vaginal bacterial species of postmenopausal women under oral estrogen therapy (Premarin-conjugated equine estrogen, CEE). STUDY DESIGN: Nineteen postmenopausal women under CEE treatment were recruited and their vaginal flora were analyzed during 3 months, using polymerase chain reaction in combination with denaturing gradient gel electrophoresis (DGGE) and sequencing of DNA fragments. RESULTS: Sixty-eight percent of the women presented with a 'Normal' Nugent score at the first sampling time (d0). All the subjects had bacterial species detected in their vaginal flora. Lactobacillus species were detected in all samples. Moreover, 53% of the women had lactobacilli exclusively at d0. Two Lactobacillus species were dominant, and were recovered from the majority of samples (L. iners and L. crispatus). Forty-four percent of the samples also contained other bacterial species, which were potential urogenital pathogens. Candida albicans was detected in 26% of the subjects. The vaginal flora of the women under CEE treatment were different from that of postmenopausal women not receiving hormone therapy, but very similar to premenopausal women. CONCLUSIONS: The present study indicates that one benefit from hormone replacement therapy (HRT) is the restoration of a lactobacilli vaginal flora associated with a protective effect against urogenital infections.
Microbes make up a significant component of the human body, yet relatively little is known about how they influence health and disease. They colonize after birth by chance and circumstance, yet play a major role in immunity, digestion, and protection against disease. In relatively recent times, basic science and clinical studies have clearly shown the potential impact of indigenous and exogenous microbes on human health and well-being. Yet regulatory bodies, research funding agencies, and health care practitioners, perhaps disillusioned by too many unreliable, overhyped products that are marketed under the guise of probiotics or natural therapeutics, have lagged far behind in embracing this avenue of enquiry. As more scientifically proven probiotic products differentiate themselves from untested and unproven cure-alls, and as multidisciplinary research groups piece together the diverse components of the puzzle, humans will slowly begin to understand how best to optimize their coexistence with microbial organisms, thus perhaps prolonging and enhancing life.
Urogenital infections are a major reason that women visit their family physician and are referred to gastroenterology, gynecology, urology, and infectious disease specialists. The association between abnormal vaginal microbiota and increased risk for sexually transmitted infections, bladder and vaginal infections per se, and a higher rate of preterm labor indicate the need to better understand and manage urogenital health. The concept of probiotics arose from the realization that humans are inhabited with microbes from birth and that these organisms play a role in preventing disease. Defined as "live microorganisms, which when administered in adequate amounts confer a health benefit on the host," probiotic strains have already been shown to effectively prevent diarrhea and to hold potential in preventing and treating tonsillitis, caries, renal calculi, and respiratory infections. This review provides a rationale for the use of probiotics in maintaining female vaginal and bladder health and as a treatment option for recurrent bacterial vaginosis, urinary tract infection, yeast vaginitis, and sexually transmitted infections. We consider only probiotic strains that fulfill the United Nations/World Health Organization Guidelines for Probiotics in being fully characterized and clinically documented through scientific investigations describing known or presumed mechanisms of action. Although medical practitioners as yet are unable to access these probiotic strains, an awareness of recent and ongoing research for probiotics is important, as results are encouraging. The concept of probiotic therapy is familiar to many consumers and although it has historically lacked credibility in the medical community, perceptions are changing.
SELDI-TOF-MS is a highly sensitive protein-analysis tool capable of detecting minute protein profile differences between biological samples. As proteins have been associated with urinary tract calculi, protein-based urinalysis may offer insights into their diagnosis. The purpose of this study was to evaluate SELDI-TOF-MS as a potential method for identifying urinary biomarkers of urolithiasis. Midstream sterile urine samples were obtained from 25 male patients with a confirmed diagnosis of urolithiasis (test group) and 25 male subjects with no known history of the disease (controls). Urinary levels of oxalate, total protein, albumin, and osteopontin were determined. Protein profiles were generated using SELDI-TOF-MS.SELDI-TOF-MS profiling revealed a relationship between protein peak intensities at 67 and 24 kDa that differed between the two groups. The ratio of p67:p24 was found to be less than 1.0 in all of the control samples (mean 0.26), while 18 out of 25 (72%) of the test group samples displayed a ratio greater than 1.0 (total group mean 4.75, P<0.001). Albumin, total protein, and oxalate levels were higher in the test group than the controls. Although SELDI-TOF-MS is not yet in widespread use in hospital and diagnostic laboratories, this system represents a promising new method for rapidly identifying patients with urolithiasis.
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Bacterial vaginosis (BV) is a common condition in women that represents an imbalance of the vaginal microflora, lactobacilli depletion, and excess growth of mainly anaerobic Gram-negative pathogens. Diagnosis is made using a series of tests or a Gram stain of a vaginal smear. Treatment with antibiotics is quite effective, but recurrences are common. A study of 55 vaginal samples from 11 postmenopausal women showed the presence of BV by the Gram stain-based Nugent scoring system, and polymerase chain reaction-denaturing gradient gel electrophoresis showed that Bacteroides or Prevotella species were the most common isolates recovered (24 of 25), with Escherichia coli, Staphylococcus aureus, and Streptococcus agalactiae also found in some samples. In one case, only Gardnerella vaginalis was found. These findings illustrate that BV remains common even among otherwise healthy women, but it is not caused solely by either Gardnerella or Mobiluncus. Use of a FemExam system (Cooper Surgical, Shelton, CT), based upon elevated pH and trimethylamine levels, to screen vaginal smears from 59 healthy women showed poor correlation with the Gram stain method. A randomized, placebo-controlled trial of these subjects showed that the lactobacilli-dominant microbiota was restored in subjects with BV but not in controls, following 2 months of daily oral intake of Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14. These studies show that nucleic acid-based methods are effective at identifying bacteria responsible for BV. If such methods could be used to develop a commercially available, self-use kit, women would be much better placed to take control of their own health, for example, using medicinal food or dietary supplement products such as the clinically proven probiotic strains L. rhamnosus GR-1 and L. fermentum RC-14.
PURPOSE: As a result of endourological advances, biomaterials have become increasingly used within the urinary tract. This review article provides an update on the current status of urinary tract biomaterials, discussing issues of biocompatibility, biomaterials available for use, clinical applications and biomaterial related complications. Perspectives on future materials for use in the urinary tract are also provided. MATERIALS AND METHODS: We performed a comprehensive search of the peer reviewed literature on all aspects of biomaterials in the urinary tract using PubMed and MEDLINE. All pertinent articles were reviewed in detail. RESULTS: Any potential biomaterial must undergo rigorous physical and biocompatibility testing prior to its commercialization and use in humans. There are currently many different bulk materials and coatings available for the manufacturing of biomaterials, although the ideal material has yet to be discovered. For use in the urinary tract, biomaterials may be formed into devices, including ureteral and urethral stents, urethral catheters and percutaneous nephrostomy tubes. Despite significant advances in basic science research involving biocompatibility issues and biofilm formation, infection and encrustation remain associated with the use of biomaterials in the urinary tract and, therefore, limit their long-term indwelling time. CONCLUSIONS: Prosthetic devices formed from biomaterials will continue to be an essential tool in the practicing urologist's armamentarium. Ongoing research is essential to optimize biocompatibility and decrease biomaterial related complications such as infection and encrustation within the urinary tract. Future advances include biodegradables, novel coatings and tissue engineering.
For the survival of humankind, nothing can be as important as the health of a mother and a child. As the world's population grows to more than 6 billion, it might seem ridiculous to suggest that any real threat exists to the human species. Diseases have long ravaged populations, as have wars, poverty, and malnutrition. Life today is no different with new and emerging diseases such as SARS and Mad Cow Disease leaving a trail of concern around the planet. All that being said, the AIDS crisis is threatening humans like no other. In countries such as Botswana, close to half the population of pregnant women is infected. Of great concern, the disease is now prevalent among women and teenage girls, threatening not only their lives but those of their offspring. Efforts to control this spread are quite abysmal, albeit well intentioned. Likewise, the death of a child every 15 seconds from diarrheal disease is not being addressed with the same vigor as SARS, even though the risk of dying from the latter for most people is similar to being struck by lightning. In the end, it is the economy and politics that dictate health spending. Image and perception are everything. While deaths mount among women and children from AIDS and other infections, the potential to intervene with a low-risk natural concept of probiotics seemed all too distant. As evidence mounts of the attributes of certain probiotic strains to treat diarrhea and reduce the risk of urogenital and other diseases, the developing world has failed to embrace it, support its evaluation and implementation, and take it to where it is needed the most. In this review, the case for and against probiotics for urogenital and intestinal infections is presented based on current literature. The story is far from complete, but the potential for improving the health of the mother and child is significant. United Nations and World Health Organization guidelines have now been developed to vanquish the unproved marketing hype products that have given probiotics a bad name. It is now up to science to deliver the remedies, and to society to make sure that only proven products reach the marketplace and the people in most need.
OBJECTIVE: The objective of this study was to examine the receptivity for probiotic products among premenopausal female students in an African university. GOAL: The goal of this study was to determine the local knowledge in Nigeria of probiotics and the willingness of young women to use them should they be introduced. STUDY: Closed-ended questionnaires were administered to a sample of 280 participants and these addressed age, marital status, perceived risk of HIV infection for the next 3 years, and history of urogenital infections. The participants were also asked whether they would welcome a probiotic product in oral/vaginal form and in milk-based food products, willingness to purchase and use, how often they would use these products, preference of form, price, and where they would like to buy the products. The second questionnaire was open-ended. It asked the participants to freely list any concerns or worries they had in relation to probiotic products. RESULTS: Of the 280 participants, 55.3% indicated that they believed they were at risk of acquiring HIV within the next 3 years, illustrating the enormity of the problem in Africa and the feelings among women that they cannot easily control sexual relationships and have partners use condoms. Eighty-two percent of the subjects stated they would welcome probiotic products in capsular form for vaginal instillation or to be taken orally to improve vaginal health. Over one third (36%) of women indicated they would be willing to use the probiotic products as part of their daily self-care. One hundred nine (39.6%) respondents were willing to purchase the probiotic products at a reasonable price of 0.08 US dollars per dose, whereas 71.5% were willing to pay up to 0.38 US dollars. Some subjects (25%) raised some concern over safety of probiotics. CONCLUSIONS: The findings revealed that female university students are receptive to probiotic products in Nigeria and indicate strongly a need to consider women's concerns about urogenital health. Furthermore, the study identified a need for appropriate educational materials about probiotics, including benefits and safety information, in an African country suffering severely from the HIV epidemic.
We sequenced 16S rRNA genes from the vaginal swab contents of a postmenopausal woman with asymptomatic bacterial vaginosis (BV). Sequences from Atopobium vaginae were the most commonly detected. In a survey of 35 other postmenopausal women, this organism was detected in 44% with BV but not in any subjects deemed healthy.
BACKGROUND: Probiotics--live microorganisms that confer a health benefit when taken in adequate amounts, usually as food supplements--are receiving renewed attention in the medical community. Some have been found to play a role in disease remediation. However, mainstream medicine and science remain divided about the validity of health claims made about them. METHODS: To clarify the potential value of probiotics, we reviewed the scientific data on their role in preventing and treating surgical infections as well as some of our own studies of the effects of certain strains of lactobacilli on surgical implant infections. PRINCIPAL FINDINGS: There is little rigorous evidence that probiotics may be beneficial in the prevention and treatment of wound infections. However, data from 3 clinical trials and from our laboratory indicate that certain strains of probiotic lactobacilli and their byproducts may help reduce infection rates in surgical patients and may ameliorate staphylococcus-related infections of surgical implants. CONCLUSION: Although there is good clinical evidence that certain probiotics may be beneficial in conditions such as diarrheal and inflammatory bowel diseases, more studies are required to apply these concepts to the prevention and treatment of wound and other surgical infections.
Urogenital infections afflict an estimated one billion people each year. The size of this problem and the increased prevalence of multi-drug resistant pathogens make it imperative that alternative remedies be found. A randomized, placebo-controlled trial of 64 healthy women given daily oral capsules of Lactobacillus rhamnosus GR-1 and Lactobacillus fermentum RC-14 for 60 days showed no adverse effects. Microscopy analysis showed restoration from asymptomatic bacterial vaginosis microflora to a normal lactobacilli colonized microflora in 37% women during lactobacilli treatment compared to 13% on placebo (P=0.02). Lactobacilli were detected in more women in the lactobacilli-treated group than in the placebo group at 28 day (P=0.08) and 60 day (P=0.05) test points. Culture findings confirmed a significant increase in vaginal lactobacilli at day 28 and 60, a significant depletion in yeast at day 28 and a significant reduction in coliforms at day 28, 60 and 90 for lactobacilli-treated subjects versus controls. The combination of probiotic L. rhamnosus GR-1 and L. fermentum RC-14 is not only safe for daily use in healthy women, but it can reduce colonization of the vagina by potential pathogenic bacteria and yeast.