Systematic review: probiotics in the management of lower gastrointestinal symptoms - an updated evidence-based international consensus.

BACKGROUND: In 2013, a systematic review and Delphi consensus reported that specific probiotics can benefit adult patients with irritable bowel syndrome (IBS) and other gastrointestinal (GI) problems. AIM: To update the consensus with new evidence. METHODS: A systematic review identified randomised, placebo-controlled trials published between January 2012 and June 2017. Evidence was graded, previously developed statements were reassessed by an 8-expert panel, and agreement was reached via Delphi consensus. RESULTS: A total of 70 studies were included (IBS, 34; diarrhoea associated with antibiotics, 13; diarrhoea associated with Helicobacter pylori eradication therapy, 7; other conditions, 16). Of 15 studies that examined global IBS symptoms as a primary endpoint, 8 reported significant benefits of probiotics vs placebo. Consensus statements with 100% agreement and "high" evidence level indicated that specific probiotics help reduce overall symptom burden and abdominal pain in some patients with IBS and duration/intensity of diarrhoea in patients prescribed antibiotics or H. pylori eradication therapy, and have favourable safety. Statements with 70%-100% agreement and "moderate" evidence indicated that, in some patients with IBS, specific probiotics help reduce bloating/distension and improve bowel movement frequency/consistency. CONCLUSIONS: This updated review indicates that specific probiotics are beneficial in certain lower GI problems, although many of the new publications did not report benefits of probiotics, possibly due to inclusion of new, less efficacious preparations. Specific probiotics can relieve lower GI symptoms in IBS, prevent diarrhoea associated with antibiotics and H. pylori eradication therapy, and show favourable safety. This study will help clinicians recommend/prescribe probiotics for specific symptoms.

Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice -- an evidence-based international guide.

BACKGROUND: Evidence suggests that the gut microbiota play an important role in gastrointestinal problems. AIM: To give clinicians a practical reference guide on the role of specified probiotics in managing particular lower gastrointestinal symptoms/problems by means of a systematic review-based consensus. METHODS: Systematic literature searching identified randomised, placebo-controlled trials in adults; evidence for each symptom/problem was graded and statements developed (consensus process; 10-member panel). As results cannot be generalised between different probiotics, individual probiotics were identified for each statement. RESULTS: Thirty seven studies were included; mostly on irritable bowel syndrome [IBS; 19 studies; treatment responder rates: 18-80% (specific probiotics), 5-50% (placebo)] or antibiotic-associated diarrhoea (AAD; 10 studies). Statements with 100% agreement and 'high' evidence levels indicated that: (i) specific probiotics help reduce overall symptom burden and abdominal pain in some IBS patients; (ii) in patients receiving antibiotics/Helicobacter pylori eradication therapy, specified probiotics are helpful as adjuvants to prevent/reduce the duration/intensity of AAD; (iii) probiotics have favourable safety in patients in primary care. Items with 70-100% agreement and 'moderate' evidence were: (i) specific probiotics help relieve overall symptom burden in some patients with diarrhoea-predominant IBS, and reduce bloating/distension and improve bowel movement frequency/consistency in some IBS patients and (ii) with some probiotics, improved symptoms have led to improvement in quality of life. CONCLUSIONS: Specified probiotics can provide benefit in IBS and antibiotic-associated diarrhoea; relatively few studies in other indications suggested benefits warranting further research. This study provides practical guidance on which probiotic to select for a specific problem.

The prenatal visit.

In their role as advocates for children and families, pediatricians are in an excellent position to support and guide parents during the prenatal period. Prenatal visits allow the pediatrician to gather basic information from parents, provide information and advice to them, and identify high-risk situations in which parents may need to be referred to appropriate resources for help. In addition, prenatal visits are the first step in establishing a relationship between the pediatrician and parents and help parents develop parenting skills. The prenatal visit may take several possible forms depending on the experience and preferences of the parents, competence and availability of the pediatrician, and provisions of the health care plan.

Assessment and treatment of dementia in medical patients.

The incidence of dementia rises rapidly with age. Elderly people commonly have significant medical conditions that impact on cognition and functional ability. The diagnosis of dementia requires both a decline in cognition and loss of functional ability. Assessment of dementia in medical patients requires a holistic approach that encompasses the spectrum of disease from measuring impairment of specific mental abilities to evaluating handicap in the patient's normal social setting. Similarly, treatment can be aimed at any point in this spectrum. Recent licensing of new cholinesterase inhibitors for the treatment of Alzheimer's disease has introduced specific problems in the treatment of medical patients with dementia. This review provides a framework for clinicians to assess and treat dementia in medical patients and describe s a practical approach to the prescribing of cholinesterase inhibitors in patients with concomitant medical problems.

Hydroxyapatite composites designed for antibiotic drug delivery and bone reconstruction: a caprine model.

The purpose of this study was to investigate the feasibility of fabricating a drug delivery system that serves a dual function, to eradicate infection as well as to provide a scaffold for osseous integration. Two porous composite systems were fabricated using hydroxyapatite (HA) as the carrier for gentamicin sulfate (GS), an aminoglycoside antibiotic. Structural and mechanical properties of porous HA-GS composites were characterized and the in vitro release behavior of GS from fabricated composites was monitored and compared with the well-known polymethylmethacrylate (PMMA)-GS delivery system. Scanning electron microscopy revealed a macropore range of 150 to 200 microm and 100 to 190 microm for the sintered and unsintered HA-GS composites, respectively. The effect of GS inclusion on bone apposition and ingrowth was assessed using a caprine model. Plugs 10 mm x 6 mm of cylindrical tricalcium phosphate, sintered HA, and sintered HA-GS were implanted in the femoral diaphysis for a period of 6 weeks. Data collected during the in vitro study showed that GS can successfully be incorporated into HA and used as a drug delivery system to eradicate Staphylococcus aureus. In vivo data confirmed that the inclusion of GS within a ceramic matrix did not stimulate or inhibit osteointegration or bone apposition. In conclusion, the fabricated sintered HA-GS composite may be beneficial in the treatment of infected osseous sites as a drug delivery system.

Cell wall antigens of Pneumocystis carinii trophozoites and cysts: purification and carbohydrate analysis of these glycoproteins.

We have purified and biochemically analyzed individual cell wall glycoproteins of Pneumocystis carinii. Our results show that corresponding core glycoproteins constitute the cell wall antigens in both trophozoites and cysts, and glycosylation of these glycoproteins does not appear to be significantly altered during development. Cysts and trophozoites in rat-derived organism preparations were separated from each other by counterflow centrifugal elutriation, then treated with Zymolyase to obtain the cell wall fractions. Gel electrophoresis patterns of these fractions from both life-cycle stages were qualitatively similar. Ten major antigenic glycoproteins in these fractions were purified by preparative continuous elution gel electrophoresis. All ten glycoproteins from cysts and trophozoites contained mannose, glucose, galactose, and N-acetylglucosamine, and some contained traces of fucose. The glycoproteins of cysts had more mannose than their trophozoite counterparts. The trophozoite glycoproteins differed from those of the cyst by the presence of xylose. To examine the species-specificity of glycoprotein glycosylation, preparations of human-derived P. carinii (comprised of mixed life-cycle stages) were also examined and found to contain the same sugars as those found in rat-derived organisms. Most of the purified rat-derived glycoproteins bound Concanvalin A, which was abolished by treatment with N-glycanase. This suggested that the majority of the oligosaccharides were N-linked to the proteins, but attempts to identify carbohydrate linkage sites by amino acid sequencing were hampered by apparent modifications of residues. The peptides derived by cyanogen bromide cleavage revealed distinct size patterns for each glycoprotein, suggesting that they were distinct proteins. Most of the glycoproteins reacted with monoclonal antibodies which recognize a highly conserved epitope on rat P. carinii. Four of the individually purified glycoprotein preparations elicited in vitro cellular immune responses, implicating their involvement in the recognition of P. carinii by host T cells. The identification and characterization of P. carinii cell wall proteins will be helpful in analyzing the relationship of the organism to its mammalian host.

Fractionation of Pneumocystis carinii developmental stages by counterflow centrifugal elutriation and sequential filtrations.

Immunomagnetic sorting, sequential filtrations, and counterflow centrifugal elutriation were compared for their ability to obtain enriched populations of Pneumocystis carinii developmental stages from infected rat-lung homogenates. Elutriation combined with sequential filtrations resulted in highly (> 95%) enriched populations of P. carinii cysts and trophozoites with excellent viability. This approach offers advantages over previously described methods of obtaining enriched P. carinii cell populations and should have important applications to research on this organism.

School-based clinic use and school performance.

School-based health clinics (SBCs) have been promoted as an innovative approach to providing adolescent health care. The present study examined the effect of a SBC on academic success. We studied the effect of clinic registration and use on students' absence, suspension, withdrawal, and graduation or promotion rates in an alternative high school for students who were not able to succeed in traditional educational programs. On average, these 322 high-risk students attended school only 56% of the time; 24% were suspended; and only 26% graduated or were promoted. The 189 (59%) students who were registered to use the clinic and the 159 (49%) who actually used the clinic were as likely to be absent or to be suspended as non-registered students. However, students who used the clinic were significantly more likely to stay in school, and to graduate or be promoted than students who were not registered for the clinic. This relationship was strongest for black males; those who used the clinic were nearly three times [odds ratio = 0.35; 95% confidence interval (CI) = (0.16-0.78)] more likely to stay in school than those who did not use the clinic. In multiple linear regression models predicting school performance, only clinic use and percent of enrolled days absent were significantly associated with graduation/promotion, and these two variables predicted 23% of the variance in promotion status.

Inhibitors of folic acid synthesis in the treatment of experimental Pneumocystis carinii pneumonia.

Inhibitors of folic acid synthesis were compared alone and in different combinations in the therapy of pneumocystosis in immunosuppressed rats. Sulfonamides (sulfamethoxazole, sulfadiazine, and sulfadoxine) and sulfones (dapsone) used alone were very active against Pneumocystis carinii, as judged by histologic examination of the lungs and by organism quantitation. Improved efficacy could not be demonstrated by the addition of an inhibitor of dihydrofolate reductase to the regimen. Dihydrofolate reductase inhibitors (trimethoprim, diaveridine, and pyrimethamine) used alone were ineffective against P. carinii. All drugs were well tolerated except pyrimethamine, which caused bone marrow depression; folinic acid ameliorated this adverse reaction but did not interfere with P. carinii treatment. These data have potential clinical implications but need to be interpreted with caution and in light of other systems of P. carinii drug evaluation.

Comparison of histologic and quantitative techniques in evaluation of therapy for experimental Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia was induced in rats by the administration of corticosteroids, and histologic and quantitative techniques were compared in the evaluation of the severity of the disease and response to therapy. A highly significant correlation was found between the histologic score of the extent of alveolar involvement (the standard method of assessment) and the number of P. carinii cysts and nuclei in lung homogenates, lung weight, and lung weight/body weight ratio. Clear differences were noted between rats which responded well and rats which responded poorly to therapy by all techniques. Quantitation of P. carinii cysts and nuclei revealed a 10(4)-fold reduction in organism burden with successful treatment. Thus, these techniques should be helpful in the development of testing of new antimicrobial agents in the rat model of pneumocystosis.

Effect of three loop diuretics and prostaglandins E2 & I2 on the isolated perfused rat mesenteric vasculature.

Rat superior mesenteric vascular bed was isolated, perfused by the artery with Krebs solution and the perfusion pressure monitored. Dose-response curves to noradrenaline and KCl administered as bolus doses were obtained. A 1 hr continuous infusion of either piretanide (10 micrograms ml-1) frusemide (40 micrograms ml-1) or bumetanide (2 micrograms ml-1) decreased the sensitivity of the preparation to noradrenaline but not to KCl. This effect was antagonized by flurbiprofen (12 micrograms ml-1) pretreatment. A 1 hr continuous infusion of prostaglandin (PG)E2 increased the sensitivity of the preparation to both noradrenaline and KCl. PGI2 (5 ng bolus) or diuretic perfusion antagonized the responses to noradrenaline but not those to KCl. PGI2 and diuretics in combination further decreased the responsiveness of the preparation to noradrenaline. KCl responses were unaffected by either PGI2 or diuretics, alone or combined. The results suggest that the loop diuretics decrease the responsiveness of the isolated rat superior mesenteric vascular bed preparation to noradrenaline, possibly by increasing the level of PGI2, an effect which may be an important factor in the cardiovascular activity of the diuretics.

Effect of bumetanide, frusemide and prostaglandin E2 on the isolated perfused kidney of rat and rabbit.

Rat and rabbit kidneys were isolated, perfused via the renal artery with Krebs solution and perfusion pressure monitored. Dose-response curves to noradrenaline administered as bolus doses or frequency-response curves from transmural arterial electrical stimulation were obtained. A 1 h continuous infusion of bumetanide (0.1 micrograms ml-1) increased the sensitivity of rat kidney vessels to noradrenaline, an effect also seen when bumetanide and flurbiprofen (6 micrograms ml-1) were simultaneously perfused. In the rabbit there was a decreased sensitivity to both electrical stimulation and noradrenaline. A 1 h continuous infusion of frusemide (6 micrograms ml-1) only altered the effects of electrical stimulation. An increased sensitivity in the rat (abolished by flurbiprofen) and a decreased sensitivity in the rabbit kidney was observed. A 1 h continuous infusion of prostaglandin (PG)E2 (2 ng ml-1) increased the sensitivity of rat kidney to both types of stimuli but caused a reduction in the responsiveness of the rabbit kidney to electrical stimuli only. Addition of flurbiprofen only slightly modified these results. The results emphasize and confirm the fundamental difference in reactivity of the rat and rabbit kidney. Bumetanide and frusemide, two ostensibly similar loop diuretics, show significantly different effects on these preparations suggesting that any modification by non-steroidal anti-inflammatory drugs cannot wholly be explained by similar PGE2 induced haemodynamic changes.

On the pharmacological actions of a diuretic, fenquizone, with particular reference to its site of action.

The pharmacological actions of a diuretic drug, fenquizone have been investigated and its effects compared with well characterized diuretics in rats, mice and rabbits. Changes in sodium and potassium excretion and urine volume were similar in magnitude and duration to those of the thiazide diuretics over dose range 0.05-100 mg kg-1. Free water clearance in rabbits was decreased indicating an action at the cortical diluting site in the nephron and since free water reabsorption was relatively unaffected it appears unlikely to have actions at other sites. Calcium and phosphate excretion studies also suggested that the predominant effects are those occurring at the cortical diluting segment of the nephron. Additional parameters not affected by the drug were blood flow to the cortex and medulla of the kidney (and other major organs), plasma glucose concentration and plasma urate concentration.

Glomerular filtration rate and kidney blood flow in alloxan and streptozotocin diabetic rats.

Glomerular filtration rate (GFR), cardiac output, regional blood flow and kidney weight were measured in alloxan and streptozotocin diabetic rats at different times after the administration of diabetogen. A high GFR was found together with increased kidney weight and reduced blood flow.

Comparison between spontaneously beating atria from control and streptozocin-diabetic rats.

Isolated spontaneously beating atria from streptozocin diabetic rats were compared with those from controls. Diabetic atria were found to have reduced rates, increased forces of contraction and reduced sensitivity to the inotropic effects of noradrenaline, isoprenaline, tyramine and calcium. Positive chronotropic responses to tyramine were also reduced but those to noradrenaline and isoprenaline were increased suggesting that tyramine releasable stores of noradrenaline were reduced. Elevation of glucose concentration in the medium from 5.6 to 27 mM resulted in decrease of inotropic sensitivity to the agents used in both control and diabetic rat atria. Resting contractile force of control rat atria was reduced by the inclusion of either 22 mM 2-deoxyglucose, 10(-3) i.u. insulin ml-1 or 5 mM acetate in the medium. The rate was also reduced by medium containing 2-deoxyglucose but increased by insulin. 2-Deoxyglucose also reduced inotropic but increased chronotropic sensitivity to isoprenaline. Possible mechanisms responsible for the changes observed are discussed.

Effects of experimental diabetes and genetic obesity on regional blood flow in the rat.

Blood flow through various tissues of streptozotocin- and alloxan-diabetic and genetically obese rats was compared with that of controls by a radioisotopically labeled microsphere technique. Total cardiac output per unit body weight was unchanged in the diabetic group but decreased in the obese animals. The proportion of cardiac output received by the kidney and organs of the gastrointestinal tract was increased in the diabetic animals. Tissue hyperplasia appeared to be largely responsible. Blood flow per unit weight was markedly increased in the fat tissue of diabetic rats but was reduced in that of the obese rats, indicating a positive relationship between fat mobilization and blood flow. Blood flow in the hindlimbs, tail, skin, and spleen were all reduced in at least one diabetic group. Most of the changes observed appeared to progress with the duration of diabetes. Possible hormonal and metabolic causes are discussed. Some of the experimental changes observed may form useful models for diabetic vasculopathy.