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The spectrum of irritable bowel syndrome: A clinical review.

BACKGROUND: Irritable bowel syndrome (IBS) is associated with a substantial burden on individual patients, health care systems, and society as a whole. OBJECTIVES: This review article provides an overview of the disease state and discusses treatment options. METHODS: The MEDLINE database was searched for original research and review articles published in English (from 1966 to July 2005) using the medical subject heading irritable bowel syndrome and the following subheadings: diagnosis, economics, pathophysiology, and therapy. Preference was given to articles that focused on new insights regarding pathophysiology and to those that addressed global symptom improvement for IBS. RESULTS: Symptoms of IBS vary with each patient and disease episode. Although improvement in individual IBS symptoms is desirable, the overall goal in managing patients with IBS is to achieve global symptom improvement. Traditional IBS therapies (ie, psychotherapy/behavioral therapy, bulking agents, antidiarrheals, antispasmodics, and tricyclic antidepressants) have lacked demonstrable efficacy in randomized controlled trials. Recent improvements in the understanding of IBS pathophysiology, particularly regarding the role of neurotransmitters and hormones in gastrointestinal motility, secretion, and visceral perception, have resulted in the development of novel treatments for IBS. In clinical trials, IBS-specific treatments (ie, agents that affect serotonergic pathways) have been associated with significant improvements in global symptoms. However, the added cost of treatment with these agents and the potential risks of serious adverse events (eg, severe constipation, severe diarrhea, ischemic colitis) may preclude their widespread use. Initial cost-effectiveness analyses with the novel IBS-specific agents suggest the benefits may outweigh the added costs. From a managed care perspective, the costs incurred by IBS-specific therapies may be offset by subsequent reductions in health care resource utilization by patients with IBS. CONCLUSIONS: IBS-specific agents offer an opportunity for patients with IBS to achieve global symptom improvement. However, when weighing the costs and potential risks against the potential benefits, clinicians should consider the nature and severity of the patient's symptoms, the degree of functional impairment, and the presence of psychosocial comorbidities.

Absenteeism↗

Determinants of persistence with bisphosphonates: a study in women with postmenopausal osteoporosis.

BACKGROUND: Although bisphosphonates are useful in the management of osteoporosis, patients often discontinue treatment. OBJECTIVES: The aims of this study were to investigate persistence with bisphosphonates, and to assess whether the dose interval influenced persistence, among women with postmenopausal osteoporosis. METHODS: Data were obtained from the PHARMO Record Linkage System, which includes, among other databases, drug-dispensing records from community pharmacies linked to hospital discharge records of > 1 million subjects in defined areas in The Netherlands. Women who were new users of alendronate (daily or weekly), etidronate (daily), or risedronate (daily) during the period from January 2000 through September 2003 were eligible for inclusion in the study if they were aged > or = 55 years or had been hospitalized for a menopausal disorder. One-year rates of persistence with treatment (defined as the percentage of patients who used the drug for > or = 365 days without failure to continue renewals) were determined by using episodes of bisphosphonate treatment. The association between persistence and dose intervals, type of bisphosphonate, and other determinants (including age, occurrence of gastrointestinal adverse events as measured by use of concomitant medications [eg, antacids, proton pump inhibitors, histamine2 (H2)-receptor antagonists, misoprostol, laxatives, antidiarrheals, bowel motility enhancers] and fractures) was assessed. To study whether persistence with bisphosphonates was associated with the former use of other antiosteoporosis medication or the presence of drug-induced osteoporosis, the use of hormone replacement therapy, raloxifene, and systemic corticosteroids in the 6 months before the index date were included as determinants. RESULTS: The study sample included 2124 women who were new users of bisphosphonates. The mean (SD) age of the study population was 71.6 (8.7) years. After 1 year, 51.9% of weekly alendronate users and 30.1% to 42.2% of daily bisphosphonate users were persistent. In the multivariate analysis (which included age, concomitant medication, and fractures), patients using alendronate weekly were significantly more likely to persist than those using alendronate daily (relative risk [RR], 1.56 [95% CI, 1.32-1.85]). The likelihood of persistence was similar among those who used the daily regimens of risedronate, etidronate, and alendronate. The occurrence of gastrointestinal adverse events was associated with decreased persistence with bisphosphonates (H2)-receptor antagonists: RR, 0.71 [95% CI, 0.53-0.94]; bowel motility enhancers: RR, 0.78 [95% CI, 0.65-0.94]). CONCLUSIONS: In this study, dose interval and the occurrence of gastrointestinal adverse events were independent determinants of persistence with bisphosphonate therapy. Although the likelihood of persistence with bisphosphonate use was significantly higher among those who used a less frequently administered regimen, persistence rates were still suboptimal.

Age Factors↗

Gastrointestinal pharmacology: irritable bowel syndrome.

Over the past 30 years, the main treatment of irritable bowel syndrome has aimed to normalize gastrointestinal transit using either laxatives or antidiarrheal agents, with or without the concurrent use of spasmolytics. The recent introduction of serotonin-related drugs has stimulated investigations into the pathophysiology of irritable bowel syndrome, including an evaluation of visceral sensitivity. At the same time, more information has been acquired on the status of the local immune system as a possible cause for sensitization of nerve terminals. Such investigations have stimulated the emergence of new concepts and original candidate drugs for the treatment of this functional disorder. Particular attention is devoted to the correction of visceral hyperalgesia.

Animals↗

(+)-Cannabidiol analogues which bind cannabinoid receptors but exert peripheral activity only.

Delta9-Tetrahydrocannabinol (Delta9-THC) and (-)-cannabidiol are major constituents of the Cannabis sativa plant with different pharmacological profiles: (-)-Delta9-tetrahydrocannabinol, but not (-)-cannabidiol, activates cannabinoid CB1 and CB2 receptors and induces psychoactive and peripheral effects. We have tested a series of (+)-cannabidiol derivatives, namely, (+)-cannabidiol-DMH (DMH-1,1-dimethylheptyl-), (+)-7-OH-cannabidiol-DMH, (+)-7-OH- cannabidiol, (+)-7-COOH- cannabidiol and (+)-7-COOH-cannabidiol-DMH, for central and peripheral (intestinal, antiinflammatory and peripheral pain) effects in mice. Although all (+)-cannabidiols bind to cannabinoid CB1 and CB2 receptors, only (+)-7-OH-cannabidiol-DMH was centrally active, while all (+)-cannabidiol analogues completely arrested defecation. The effects of (+)-cannabidiol-DMH and (+)-7-OH-cannabidiol-DMH were partially antagonized by the cannabinoid CB1 receptor antagonist N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716), but not by the cannabinoid CB2 receptor antagonist N-[-(1S)-endo-1,3,3-trimethil bicyclo [2.2.1] heptan-2-yl-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528), and had no effect on CB1(-/-) receptor knockout mice. (+)-Cannabidiol-DMH inhibited the peripheral pain response and arachidonic-acid-induced inflammation of the ear. We conclude that centrally inactive (+)-cannabidiol analogues should be further developed as antidiarrheal, antiinflammatory and analgesic drugs for gastrointestinal and other peripheral conditions.

Animals↗

Development of tolerance to the inhibitory effect of loperamide on gastrointestinal transit in mice.

The inhibitory effect of repetitiously administered loperamide, a peripheral mu-opioid receptor agonist and well-recognized antidiarrheal agent, on mouse gastrointestinal transit was compared with that of morphine in order to examine the development of tolerance to mu-opioid receptor agonist-induced constipation (antitransit effect). When administered subcutaneously 15 min before the oral injection of charcoal meal, loperamide (0.1-30 mg/kg) and morphine (1-8 mg/kg) dose-dependently and significantly inhibited gastrointestinal transit of charcoal with the ID(50) values of 1.6 (0.3-7.1) mg/kg and 3.6 (1.5-8.5) mg/kg, respectively. When loperamide (30 mg/kg) was administered twice daily for 2 days, the antitransit effect was significantly reduced. On the other hand, morphine did not develop tolerance in even more severe conditions than those of loperamide. It is known that P-glycoprotein, an ATP-dependent drug efflux pump, is involved in the development of tolerance to morphine analgesia. The tolerance observed with loperamide was significantly prevented by cyclosporin (30 mg/kg, i.p.), a P-glycoprotein inhibitor, thus the ID(50) value in loperamide-tolerant mice was markedly reduced from >1000 mg/kg to 40 (2.7-603.0) mg/kg by cyclosporin. These results indicate that loperamide, different from morphine, readily develops tolerance to the inhibitory effect on mouse gastrointestinal transit, and the P-glycoprotein may be involved in the development of tolerance to the antitransit effect of loperamide.

Animals↗

In vitro antiprotozoal activity of the leaves of Artemisia ludoviciana.

The inhabitants of Northeast of Mexico use an infusion of leaves from Artemisia ludoviciana as an antidiarrheal remedy. The aqueous, methanol, acetone and hexane leaf extracts from mature plants were found to be active in vitro against the parasitic protozoa Entamoeba histolytica and Giardia lamblia.

Animals↗

A modified inflammatory bowel disease questionnaire and the Vaizey Incontinence questionnaire are more sensitive measures of acute gastrointestinal toxicity during pelvic radiotherapy than RTOG grading.

PURPOSE: Simple scales with greater sensitivity than Radiation Therapy Oncology Group (RTOG) grading to detect acute gastrointestinal toxicity during pelvic radiotherapy, could be clinically useful. METHODS AND MATERIALS: Do questionnaires used in benign gastrointestinal diseases detect toxicity in patients undergoing radiotherapy? The patient-completed Inflammatory Bowel Disease (IBDQ) and Vaizey Incontinence questionnaires were compared prospectively at baseline and at Week 5 to physician-completed RTOG grading. RESULTS: A total of 107 patients, median age 63 years, were recruited. After 5 weeks of treatment, patients with gynecologic and gastrointestinal cancer were more symptomatic than urologic patients (p = 0.012; p = 0.014). Overall, 94% had altered bowel habits, 80% loose stool, 74% frequency, 65% difficult gas, 60% pain, >48% distress, 44% tenesmus, >40% restrictions in daily activity, 39% urgency, 37% fecal incontinence, and 40% required antidiarrheal medication. The median RTOG score was 1 (range, 0-2), median IBDQ score 204.5 (range, 74-224), and median Vaizey score 5 (range, 0-20). Chemotherapy preceding radiotherapy increased fecal incontinence (p = 0.002). RTOG scores stabilized after 3 weeks, IBDQ scores peaked at Week 4, and Vaizey scores worsened throughout treatment. IBDQ and Vaizey scores distinguished between groups with different RTOG scores. CONCLUSION: The IBDQ and Vaizey questionnaires are reliable and sensitive, offering greater insight into the severity and range of symptoms compared with RTOG grading.

Adult↗

Peripheral, but not central effects of cannabidiol derivatives: mediation by CB(1) and unidentified receptors.

Delta-9 tetrahydrocannabinol (Delta(9)-THC) and (-)-cannabidiol ((-)-CBD) are major constituents of the Cannabis sativa plant with different pharmacological profiles: (Delta(9)-THC activates cannabinoid CB(1) and CB(2) receptors and induces psychoactive and peripheral effects. (-)-CBD possesses no, or very weak affinity for these receptors. We tested a series of (+)- and (-)-CBD derivatives for central and peripheral effects in mice. None of the (-)-CBD derivatives were centrally active, yet most inhibited intestinal motility. Of the five (+)-CBD derivatives, all with CB(1) receptor affinity, only (+)-7-OH-CBD-DMH (DMH=1,1-dimethylheptyl), acted centrally, while all five arrested defecation. The effects of (+)-CBD-DMH and (+)-7-OH-CBD-DMH were inhibited by the CB(1) receptor antagonist SR141716. The CB(2) receptor antagonist SR144528, and the vanilloid TRPV1 receptor antagonist capsazepine, had no influence. Further, the (-)-CBD derivatives (-)-7-COOH-CBD and (-)-7-COOH-CBD-DMH, displayed antiinflammatory activity. We suggest that (+)-CBD analogues have mixed agonist/antagonist activity in the brain. Second, (-)-CBD analogues which are devoid of cannabinoid receptor affinity but which inhibit intestinal motility, suggest the existence of a non-CB(1), non-CB(2) receptor. Therefore, such analogues should be further developed as antidiarrheal and/or antiinflammatory drugs. We propose to study the therapeutic potential of (-)- and (+)-CBD derivatives for complex conditions such as inflammatory bowel disease and cystic fibrosis.

Animals↗

Acute diarrhea: a practical review.

This review provides a practical, simple, and logical approach to the diagnosis and management of patients with acute infectious diarrhea, one of the most common diagnoses in clinical practice. Diarrhea in the immunocompromised host, traveler's diarrhea, and diarrhea in the hospitalized patient are also discussed. Most episodes of acute diarrhea are self-limited, and investigations should be performed only if the results will influence management and outcome. After an adequate history and physical examination, the clinician should be able to classify the acute diarrheal illness, assess the severity, and determine whether investigations are needed. Most patients do not require specific therapy. Therapy should mainly be directed at preventing dehydration. Various home remedies frequently suffice in mild, self-limited diarrhea. However, in large-volume, dehydrating diarrhea, oral rehydration solutions should be used, as they are formulated to stimulate sodium and water absorption. Antidiarrheal agents can be useful in reducing the number of bowel movements and diminishing the magnitude of fluid loss. The most useful agents are opiate derivatives and bismuth subsalicylate. Antibiotic therapy is not required in most patients with acute diarrheal disorders. Guidelines for their use are presented.

AIDS-Related Opportunistic Infections↗

Functional outcome in handsewn versus stapled ileal pouch-anal anastomosis.

Eighty-eight of 119 patients who underwent ileal pouch-anal anastomosis for ulcerative colitis were evaluated. Forty patients had a handsewn anastomosis (Hs) with mucosectomy, and 48 had a stapled anastomosis (St). In each patient, we evaluated operative, morphologic, functional, and manometric features. The results in the Hs and St groups were similar when the anastomosis was within 1 cm of the dentate line. In particular, there was no correlation between the type of anastomosis and the number of bowel movements in a 24-hour period, the presence of the urge to defecate, and the use of antidiarrheal drugs. Leakage was significantly higher in the Hs group, even when the anastomosis was less than 1 cm from the dentate line. Pouchitis was more frequent in the Hs group, and, within this group, among those with a short distance between the anastomosis and the dentate line. No correlations were found between the presence of columnar epithelium or active colitis in the mucosa below the anastomosis, the functional outcomes, and the incidence of pouchitis.

Adenomatous Polyposis Coli↗

Similar functional results after restorative proctocolectomy in patients with familial adenomatous polyposis and mucosal ulcerative colitis.

Restorative proctocolectomy (RP) is generally considered to achieve better results in patients with familial adenomatous polyposis (FAP) than in those with mucosal ulcerative colitis (MUC). We studied 39 pairs of patients (FAP versus MUC), individually matched for surgeon (n = 4), types of ileal pouch (19 S-pouches and 20 J-pouches), technique of ileal pouch-anal anastomosis (21 stapled, 18 handsewn with mucosectomy), duration of follow-up after pouch function (median: 32 months; range: 6 months to 8.5 years), age (median: 30 years; range: 12 to 60 years), and gender (male-to-female ratio: 1.4:1.0). The median duration of operation (3.2 hours), hospital stay (9 days), and the amount of blood loss (about 650 mL) were similar between the two groups. The patients in the MUC group tended to have a higher overall complication rate (28% versus 21%) and more pouch-related septic complications (13% versus 8%, p = 0.6 by chi 2 analysis). Functional results were similar for daytime (median: 5 per day) and nighttime (median: 1 per night) stool frequency and the median duration that defecation could be deferred (median: about 1.5 hours). Perfect continence was present in 34 (87%) patients during the day and in 19 (49%) patients during the night in each group. The use of antidiarrheal medications did not differ between the two groups. According to an analogue scale (from 1 to 10, with 10 being best), the quality of life and health and satisfaction with outcome (median score: 9) were identical between the groups. Thus, in closely matched groups of patients with FAP and MUC, the functional outcome after RP was similar. However, pouchitis was more common in the MUC group (33% versus 10%, p < 0.05 by chi 2 analysis).

Adenomatous Polyposis Coli↗

Inflammatory bowel disease. Part II: Clinical and therapeutic aspects.

Once regarded as medical curiosities, ulcerative colitis and Crohn's disease have achieved a remarkable change in status recently and today are among the more compelling of all human illnesses. The cause(s) of inflammatory bowel disease (IBD) are not known. Genetic, environmental, microbial, and immunologic factors are involved, but the precise mechanisms are obscure. The incidence of ulcerative colitis is relatively stable, while Crohn's disease continues to increase in frequency. In 10% to 15% of patients, it is hard to differentiate between ulcerative colitis and Crohn's colitis, however, problems with diagnosis usually resolve with time and repeated examinations. In part I of his two-part monograph on IBD, Dr. Kirsner addressed the nature and pathogenesis of the disease. Increased study of ulcerative colitis and Crohn's disease in recent years has generated new knowledge regarding their etiology. Part I focused on microbial, immunologic, and genetic mechanisms of, and the inflammatory process involved in the disease. In this part, Dr. Kirsner deals with the clinical features, course, and management of IBD, based on the author's 55 years of experience with these problems and supplemented by critical examination of the recent (1988-1990) literature. Particular attention is directed to the symptoms and physical findings of ulcerative colitis and Crohn's disease. The laboratory, radiologic, endoscopic, and pathologic features, and the many systemic complications. IBDs are mimicked by several enterocolonic infections and other conditions making differential diagnosis necessary. Inflammatory bowel disease in children and the elderly conforms to conventional clinical patterns modified by the health circumstances of the respective age groups. Because the cause of IBD has not been established, current medical therapy is facilitative and supportive rather than curative. The principles of medical treatment are approximately the same for ulcerative colitis and Crohn's disease. Treatment emphasizes a program rather than a drug and also considers the individuality of the therapeutic response. A clearer understanding of dietary and nutritional needs, including hyperalimentation and electrolyte and fluid balance, aids treatment. Antidiarrheal and antispasmodal preparation and sedatives are prescribed for symptom relief. The bowel inflammation is controlled with sulfasalazine or the newer 5-amino-salicylic acid (5-ASA) compounds, antibacterial drugs for complications of Crohn's disease and IBD, adrenocortical steroids, and the immunosuppressive compounds 6-mercaptopurine (6MP), azathioprine, and cyclosporine, as determined in each patient. The surgical procedures available for treatment of ulcerative colitis include total proctocolectomy and ileostomy or ileoanal anastomosis.(ABSTRACT TRUNCATED AT 400 WORDS)

Colitis, Ulcerative↗

Involvement of K+ channel modulation in the proabsorptive effect of nitric oxide in the rat jejunum in vivo.

The role of K+ channels in the mediation of the nitric oxide(NO)-induced proabsorptive effect in intestinal fluid transport was investigated in a functional study, using a model of ligated jejunal loops of anaesthetized rats in vivo. The K+ channel opener cromakalim and the K+ channel blocker glibenclamide were administered under basal conditions as well as under conditions, when fluid secretion was influenced by N omega-nitro-L-arginine methyl ester (L-NAME), prostaglandin E2, Escherichia coli heat stable enterotoxin a (E. coli STa) or L-arginine. Intravenous infusion of cromakalim (63.5 micrograms/kg per min) significantly enhanced net fluid absorption compared to controls, totally abolished net fluid secretion induced by L-NAME (0.55 mg/kg per min), reversed net fluid secretion induced by intraluminal instillation of E. coli STa (10 units/ml) to absorption, but did not influence fluid secretion elicited by close i.a. infusion of prostaglandin E2 (79 ng/min). Close i.a. infusion of glibenclamide (0.16 mg/kg per min) reversed net fluid absorption to net secretion, blocked the absorptive effect of L-arginine (8.88 mg/kg per min) and reduced the proabsorptive effect of cromakalim. The secretory effect of L-NAME was not further enhanced by glibenclamide. These results suggest that modulation of basolateral K+ channels by NO is involved in the mediation of its proabsorptive effect, since opening and closure of K+ channels mimicked, respectively counteracted, the action of NO-donors and inhibitors of NO-synthesis on intestinal fluid transport. The role of prostaglandins in the proabsorptive effect of NO remains to be elucidated. These results furthermore support the role of K+ channel openers as potential new antidiarrheal drugs.

Animals↗

Potentiation of anaphylaxis in guinea pig ileal mucosa by a selective delta-opioid receptor agonist.

Immediate hypersensitivity reactions in the intestinal mucosa evoke active chloride secretion which enhances the elimination of luminal antigens. The prosecretory actions of histamine and other soluble mediators of anaphylaxis are mediated by submucosal neurons, as are the antisecretory actions of opioid antidiarrheal medications. We tested the hypothesis that the selective delta-opioid receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) alters anaphylaxis-associated ileal anion secretion in vitro. Sheets of ileal mucosa with attached submucosa from guinea pigs sensitized to cow's milk were mounted in Ussing chambers under short-circuit conditions. Mucosal sheets responded to the serosal application of the milk protein, beta-lactoglobulin, with a rapid rise in transepithelial short-circuit current (Isc); in contrast, the egg protein, ovalbumin, was without effect. Pretreatment of tissues with the neuronal conduction blocker, saxitoxin, or the H1 histamine receptor antagonist, diphenhydramine, but not the opioid receptor antagonist, naloxone, significantly reduced mucosal responses to antigen. [D-Pen-2, D-Pen5]enkephalin (0.1 microM, serosal addition) decreased baseline Isc, but potentiated mucosal responses to antigen; its effects were abolished in tissues pretreated with naloxone. These results suggest that immediate hypersensitivity reactions in the guinea pig ileal mucosa are mediated by submucosal neural circuits that are phasically modulated by both mast cell products and opioids.

Analgesics↗

Efficacy of open-label bismuth subsalicylate for the treatment of microscopic colitis.

BACKGROUND & AIMS: The pathogenesis of the microscopic colitis syndrome is unknown but may involve bacteria, an intestinal luminal antigen, and/or autoimmunity. It was hypothesized that bismuth subsalicylate would resolve both diarrhea and colonic inflammation in microscopic colitis because it possesses antidiarrheal, antibacterial, and anti-inflammatory properties. METHODS: Thirteen patients with microscopic colitis (7 with subepithelial collagen deposition and 6 without) were treated with eight chewable 262-mg bismuth subsalicylate tablets per day for 8 weeks. Patients recorded the frequency of bowel movements daily. Forty-eight-hour stool collections and flexible sigmoidoscopy with 24 biopsies were performed before and after treatment in each patient. RESULTS: Twelve patients completed the trial. Eleven patients had a resolution of diarrhea and a reduction in fecal weight. The average time to respond was 2 weeks. In 9 patients, colitis resolved. When present before treatment, subepithelial collagen thickening disappeared. Those completing the trial experienced no side effects. Posttreatment follow-up for 7-28 months shows that 9 patients remain well having undergone no further treatment, 2 are well but required retreatment, and 1 has continued diarrhea. CONCLUSIONS: Bismuth subsalicylate treatment for 8 weeks is safe and well tolerated. This regimen appears to be efficacious for the treatment of microscopic colitis and is worthy of further study in a controlled trial.

Administration, Oral↗

Late effects after radiotherapy for prostate cancer in a randomized dose-response study: results of a self-assessment questionnaire.

OBJECTIVES: To evaluate the late effects more than 2 years after radiotherapy using a patient-reported questionnaire in patients with prostate cancer enrolled in a randomized dose-response study comparing 70 Gy (conventional) and 78 Gy (conformal) radiotherapy (RT). METHODS: The first 112 patients in the study were sent questionnaires to evaluate late bladder, rectal, and sexual function. There were 101 evaluable responses, with 50 in the conventional (Conven-RT) arm and 51 in the conformal (3DCRT) arm. RESULTS: The overall rate of persistent incontinence was 29%, with 36% reporting urgency-related and 8% stress-related incontinence at some time after radiation. Use of a urinary protective device was required in 2%. The majority noticed leakage less than once per day (52%). In comparing the Conven-RT group with the 3DCRT group, similar incontinence rates were seen. However, fewer of those who received 3DCRT reported daily leakage of urine (33% versus 63%, P = 0.044). The majority (78%) of patients experienced no or mild change in bowel function after RT. Urgency of bowel movements (BMs) was of concern for 27% of patients; however, 90% reported their BMs were controlled without accidents, and 1% were taking antidiarrheal medications once a week or daily. The Conven-RT group had more moderate or major changes in bowel function than the 3DCRT group (34% versus 10%), more frequent BMs (47% versus 27%), and more urgent BMs (37% versus 18%) (P < or = 0.040 for all three comparisons). Hematochezia was uncommon, occurring once a week in 7% and daily in 4% of patients. Before RT, 80% of patients were potent, with erections adequate for intercourse at least a few times over the prior year. After RT, potency was decreased to 51%, with erections adequate for intercourse at least a few times since the completion of RT. CONCLUSIONS: The overall rates of significant complications were extremely low. Although 30% reported incontinence, relatively few patients (2%) required pads. This rate compares favorably with the 31% of patients requiring protection after radical prostatectomy reported previously. Despite the higher treatment doses in the 3DCRT arm, slightly fewer long-term bowel side effects were noted. These data indicate that 78 Gy may safely be delivered using the conformal RT boost treatment technique described.

Dose-Response Relationship, Radiation↗

Patient perspective of long-term outcome of augmentation cystoplasty for neurogenic bladder.

OBJECTIVES: Although the urologic outcomes of augmentation cystoplasty for neurogenic bladder dysfunction are well known, additional information about the patient perspective is needed. The aim of this study was to assess patient perspective using a standardized questionnaire. METHODS: Fifty-nine patients, who had undergone augmentation enterocystoplasty as part of reconstruction mainly to correct hyperactive bladders and incontinence, were subjected to a questionnaire after a median of 76.1 postoperative months. The questionnaire addressed medications, catheterization, incontinence, bowel dysfunction, and satisfaction with urinary tract management. The urologic outcomes regarding upper and lower tract changes, complications, and reinterventions were documented as well. RESULTS: The patients experienced a significant increase in bladder capacity and decrease in pressure at capacity (P < 0.0001). Normal upper tracts remained normal and there was either improvement or stabilization of hydronephrosis. Twenty-four patients (40.6%) had one or more complications, with 21 requiring reinterventions. Twenty-five percent of patients required the reintervention within the first 25 months, and the median time to reintervention was almost 10 years. Thirty-five patients took medications such as anticholinergics, antidiarrheals, or antibiotics. Fifty-six patients were treated with clean intermittent catheterization (CIC) at a mean interval of 4.6 hours. Seven patients had some difficulty with CIC. Thirty-nine patients (67%) were dry, and 17 had mild and 3 severe incontinence. Eleven patients (18.6%) reported bowel dysfunction, although 7 had it preoperatively. Almost all patients were very satisfied with their urologic management. CONCLUSIONS: The high degree of patient satisfaction attests to the value of the procedure. The complication and reintervention rates underscore the importance of long-term follow-up.

Adult↗

Pharmacologic management of common gastrointestinal health problems in women.

A wide variety of drugs are available for the treatment of common gastrointestinal health problems in women, including minor or serious as well as acute or chronic conditions. The midwife needs to be current in the pharmacology of over-the-counter as well as prescriptive agents for both pregnant and nonpregnant women. The drug classifications reviewed in this article include antacids, H2 receptor antagonists, antimicrobials, proton pumps, antiemetics, emetics, cholinergics, laxatives, prokinetics, and antidiarrheals. In addition, the physiologic principles are reviewed to enhance the understanding of how these drugs work.

Drug Therapy, Combination↗