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Biomedical subjects

C M Surawicz

Publications and source records attributed to C M Surawicz.

At least 37 records · Page 2Linked to original sources

Biotherapeutic agents. A neglected modality for the treatment and prevention of selected intestinal and vaginal infections.

OBJECTIVE: To evaluate the potential of biotherapeutic agents (microorganisms with therapeutic properties) for the prevention and/or treatment of selected intestinal and vaginal infections. DATA SOURCES: The MEDLINE database was searched for all relevant articles published between 1966 and September 1995. Search terms used were biotherapeutic agent, probiotic, Lactobacillus, Saccharomyces, Bifidobacterium, Candida, gastrointestinal- system, vaginitis, vaginosis-bacterial, and related terms. The bibliographies of obtained articles were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All placebo-controlled human studies on biotherapeutic agents were reviewed. English-language open trials, case series and reports, and animal studies were reviewed only if they were especially relevant to providing information on the potential efficacy, adverse effects, or mechanisms of action of these agents. DATA SYNTHESIS: Placebo-controlled studies have shown that biotherapeutic agents have been used successfully to prevent antibiotic-associated diarrhea (Lactobacillus caseiGG, bifidobacterium longum, B longum with L acidophilus, and Saccharomyces boulardii), to prevent acute infantile diarrhea (Bifidobacterium bifidum with Streptococcus thermophilus), to treat recurrent Clostridium difficile disease (S boulardii), and to treat various other diarrheal illnesses (Enterococcus faecium SF68, L caseiGG, and S boulardii). There is also evidence for Lactobacillus acidophilus in the prevention of candidal vaginitis. Few adverse effects have been reported. However, many of the studies tested only small numbers of patients or volunteers. CONCLUSIONS: There is now evidence that administration of selected microorganisms is beneficial in the prevention and treatment of certain intestinal and, possibly, treatment of vaginal infections. In an effort to decrease the reliance on antimicrobials, the time has come to carefully explore the therapeutic applications of biotherapeutic agents.

Adult↗

A parastomal hernia causing small-bowel obstruction.

A parastomal hernia is an incisional hernia that occurs at the site of an intestinal stoma on the abdominal wall. We report the case of a 52-year-old woman who had had ulcerative colitis and a total colectomy and ileostomy 9 years before being evaluated for a 2-year history of intermittent small-bowel obstruction thought initially to be due to Crohn's disease. On examination, a clear parastomal hernia was detected and confirmed by a small-bowel series. At surgery the hernia was corrected, and her intermittent episodes of small-bowel obstruction resolved. A parastomal hernia should be considered as a cause of intermittent small-bowel obstruction in anyone who has a stoma. Careful history and physical examination should suffice in establishing a diagnosis.

Colitis, Ulcerative↗

Clinical presentation of minimally invasive and in situ squamous cell carcinoma of the anus in homosexual men.

From January 1988 to December 1993, we identified six men with minimally invasive (stage I) squamous cell carcinoma of the anus and 10 men with anal carcinoma in situ (CIS). Of the six patients with invasive carcinoma, four were infected with human immunodeficiency virus (HIV), including one with AIDS. Of the 10 patients with CIS, eight were infected with HIV, including four with AIDS. Anal pain and bleeding were the most common symptoms of minimally invasive anal cancer and anal CIS. Anal irritation, burning, or pruritus occurred more frequently in patients with CIS, whereas anal ulcers, masses, or abscesses were more frequent in patients with minimally invasive cancer. Several patients with CIS had a discrete area of leukoplakia in the anal canal or a pigmented plaque of the anus and anal canal. These lesions were not observed in patients with minimally invasive anal cancer. The symptoms and signs of early-stage anal cancer in men at risk for developing HIV infection or men infected with HIV often resemble those of other common anorectal diseases in homosexual men. Anal cancer in HIV-infected men is not limited to those individuals with AIDS.

Adult↗

Prospective study of high grade anal squamous intraepithelial neoplasia in a cohort of homosexual men: influence of HIV infection, immunosuppression and human papillomavirus infection.

OBJECTIVE: To determine the risk of developing high grade anal squamous intraepithelial neoplasia (HG-AIN) in relation to HIV infection and immunosuppression, after controlling for the effects of human papillomavirus (HPV) infection. DESIGN: Prospective cohort study of 158 HIV-seropositive and 147 HIV-seronegative homosexual men presenting to a community-based clinic with initially negative anal cytologic and colposcopic findings. METHODS: Subjects completed self-administered questionnaires, underwent cytologic screening, and standardized unaided and colposcopic examination of the proximal anal canal for presence of abnormalities suggestive of AIN. Anal specimens were screened for HPV DNA. RESULTS: HG-AIN developed in eight (5.4%) and 24 (15.2%) HIV-seronegative and -seropositive men, respectively. Risk of HG-AIN among HIV-seronegative men was associated with detection of anal HPV types 16 or 18 by Southern transfer hybridization (STH), detection of HPV 16 or 18 at the lower levels by polymerase chain reaction but not by STH, and with number of positive HPV tests; HG-AIN risk among HIV-seropositive men was associated with detection of HPV 16 or 18 only by STH, detection of HPV types other than 16 or 18, CD4 count < or = 500 x 10(6)/l, and number of positive HPV tests. HIV-induced immunosuppression remained an independent predictor of HG-AIN after adjusting for type and level of detection of HPV; HIV infection predicted HG-AIN risk after adjustment for number of positive HPV tests. CONCLUSIONS: The association of HG-AIN with HIV, independent of HPV type, level of HPV detection and number of positive HPV tests, suggests that this increased risk cannot be entirely explained by an effect of HIV on HPV detection. Future studies focusing on factors more specific to the local microenvironment in the anal canal should help clarify these issues.

Adult↗

High grade anal dysplasia in visually normal mucosa in homosexual men: seven cases.

BACKGROUND: Anal cancer and anal human Papillomavirus (HPV) infection are increased in homosexual men. METHODS: We screened high risk homosexual men as part of a longitudinal study examining the effect of HIV infection on the risk of development of high grade anal intraepithelial neoplasia (AIN II, III). RESULTS: We found seven men who had histological evidence of AIN II-III with visually normal findings by anoscopy. Two men were HIV-seronegative, five were HIV-seropositive, and only one of the HIV-seropositive men had a low CD4 count < 200. Abnormal cytological results seen over follow-up periods of 3 months to 2.5 yr suggest the persistence of visually inapparent anal abnormalities. Two of the men had had small internal warts at earlier examinations, and three of the seven men subsequently developed visually abnormal anal findings. All men had HPV 16 DNA detected at some point. CONCLUSIONS: We hypothesize that high grade anal neoplasia may develop deep in the glands and can be detected by cytology before visible lesions are detected even with the aid of a colposcope. However, the implications of finding high grade anal cytology are not known at this time. Natural history studies are ongoing.

Adult↗

Prevention of beta-lactam-associated diarrhea by Saccharomyces boulardii compared with placebo.

OBJECTIVES: To determine the safety and efficacy of a new preventive agent for antibiotic-associated diarrhea (AAD) in patients receiving at least one beta-lactam antibiotic. METHODS: A double-blinded, placebo-controlled, parallel group study was performed in a high-risk group of hospitalized patients receiving a new prescription for a beta-lactam antibiotic and having no acute diarrhea on enrollment. Lyophilized Saccharomyces boulardii or placebo (1 g/day) was given within 72 h of the start of the antibiotic(s) and continued until 3 days after the antibiotic was discontinued, after which the patients were followed for 7 wk. RESULTS: Of the 193 eligible patients, significantly fewer, 7/97 (7.2%), patients receiving S. boulardii developed AAD compared with 14/96 (14.6%) on placebo (p = 0.02). The efficacy of S. boulardii for the prevention of AAD was 51%. Using a multivariate model to adjust for two independent risk factors for AAD (age and days of cephalosporin use), the adjusted relative risk was significantly protective for S. boulardii (RR = 0.29, 95% CI = 0.08, 0.98). CONCLUSION: The prophylactic use of S. boulardii given with a beta-lactam antibiotic resulted in a significant reduction of AAD with no serious adverse reactions.

Adult↗

Mucosal biopsy diagnosis of colitis: acute self-limited colitis and idiopathic inflammatory bowel disease.

BACKGROUND/AIMS: Rectal biopsy specimen changes distinguish acute self-limited colitis (ASLC) from idiopathic inflammatory bowel disease (IBD). This study aimed to determine whether these histological criteria are also valid for acute-onset IBD. METHODS: Blind analysis of colorectal biopsy specimens from 52 patients with ASLC, 51 patients with acute-onset (< 3 months) IBD, and 30 patients with chronic IBD was performed. RESULTS: Histological features of ASLC are normal crypt architecture and acute lamina propria inflammation, but mixed acute and chronic inflammation can be found. Histological features of IBD are diffusely abnormal crypt architecture, crypt atrophy, mixed lamina propria inflammation, basal plasmacytosis, basal lymphoid aggregates, basal lymphoid hyperplasia, isolated giant cells, epithelioid granulomas, goblet cell mucus depletion, and reactive epithelial hyperplasia. Changes of chronic IBD were present in biopsy specimens as early as 7 days after the onset of symptoms. CONCLUSIONS: Rectal biopsy specimens are useful in distinguishing ASLC from acute-onset IBD even if the biopsy specimens are not obtained during the first 4 days of the illness. There were no significant differences in histology between acute-onset and chronic IBD.

Acute Disease↗

Anal dysplasia in homosexual men: role of anoscopy and biopsy.

BACKGROUND: Both anal squamous cell cancer and human papilloma virus (HPV) are increased in homosexual men. This study evaluates histology of internal anal abnormalities in a high-risk population of human immunodeficiency virus (HIV) seropositive and seronegative homosexual men. METHODS: Ninety men with abnormalities of the internal anal canal (referred from a cross-sectional study of 512 homosexual men) were evaluated by anoscopy, anal cytology, and directed biopsy. CD4 cell counts from blood and HPV types from anal tissue were also obtained. RESULTS: Seventy-eight (86%) men had HPV-associated abnormalities: discrete warts in 39 (43%), a wart ring in 23 (26%), and flat white epithelium in 18 (20%). Dysplasia was detected by cytology in 36% and by biopsy in 92% (27% high grade). High-grade dysplasia was equally common in HIV-seropositive and -seronegative men. The morphology of anal lesions did not predict the presence of dysplasia. Both high- and low-risk HPV types were common in many of the biopsy specimens. CONCLUSIONS: Anal dysplasia is common in biopsy specimens from homosexual men with visible HPV-associated internal anal abnormalities. Natural history studies are needed to determine the clinical significance of anal dysplasia, rates of progression to cancer, and the role of screening and therapy.

AIDS-Related Opportunistic Infections↗

Recovery and elimination of the biotherapeutic agent, Saccharomyces boulardii, in healthy human volunteers.

Saccharomyces boulardii (Sb) is a nonpathogenic yeast used to treat intestinal illnesses such as pseudomembranous colitis and antibiotic associated diarrhea. The behavior of this biotherapeutic agent in humans was determined (1) in investigating the effect of dose on the steady-state level and recovery and (2) in quantitating the effect of ampicillin on the recovery and elimination profile. As the Sb dose increased, the mean steady-state concentration of Sb increased significantly. The percentage recovery was dose independent. When a single Sb dose was administered 24 hr after beginning a course of ampicillin, there was a significant increase (P < 0.01) in both the area under the concentration versus time curve and the maximum fecal concentration compared to values obtained without ampicillin. Ampicillin increased steady-state recovery of the drug about twofold (P < 0.05) and steady-state levels about 2.4 times (P < 0.01). These studies have shown that there is a relationship between the dose and the amount of Sb recovered and that perturbation of the GI flora by ampicillin increases steady-state levels of Sb.

Adult↗

Prevention of further recurrences of Clostridium difficile colitis with Saccharomyces boulardii.

A patient with six documented episodes of recurrent Clostridium difficile colitis over an eight-month period is described. Relapses of colitis occurred despite treatment with vancomycin, metronidazole, bacitracin, and cholestyramine. Each recurrence appeared to begin successively closer to the end of the previous course of treatment. Four episodes were sufficiently severe to require hospitalization for rehydration. Saccharomyces boulardii, a nonpathogenic yeast, was begun prior to discontinuing vancomycin therapy for the last recurrence and was continued for three months. Serial stool cultures and assays for C. difficile showed persistence of the organism but rapid reduction of high titers of cytotoxin. No further recurrences of diarrhea or colitis were encountered while the patient was taking Saccharomyces boulardii and for 18 months of follow-up after the yeast was discontinued.

Aged↗

Risk factors for Clostridium difficile carriage and C. difficile-associated diarrhea in a cohort of hospitalized patients.

A prospective cohort study of 399 consecutive patients in a single ward over an 11-month period was conducted to identify risk factors for nosocomial C. difficile colonization and diarrhea. The incidence of asymptomatic carriage was 13.0/100 patient admissions and the incidence of C. difficile-associated diarrhea was 7.8/100 patient admissions. Increased age and more severe underlying illness were associated with increased risk of C. difficile carriage and diarrhea. Multivariate models adjusting for age and severity of underlying disease associated two risk factors with asymptomatic C. difficile carriage: stool softeners (relative risk [RR] = 2.04) and antacids (RR = 1.80). Five risk factors were associated with C. difficile-associated diarrhea: cephalosporin use (RR = 2.07), penicillin use (RR = 3.41), enemas (RR = 3.26), gastrointestinal stimulants (RR = 3.06), and stool softeners (RR = 1.74). C. difficile was a common nosocomial infection on this ward, resulting in asymptomatic carriage more often than diarrhea and accounting for one-fifth of all cases of nosocomial diarrhea.

Adult↗

Prevention of antibiotic-associated diarrhea by Saccharomyces boulardii: a prospective study.

Saccharomyces boulardii, a nonpathogenic yeast, has been widely used in Europe to prevent antibiotic-associated diarrhea (AAD). We performed a prospective double-blind controlled study to investigate AAD in hospitalized patients and to evaluate the effect of S. boulardii, a living yeast, given in capsule form concurrently with antibiotics. Over 23 mo, 180 patients completed the study. Of the patients receiving placebo, 22% experienced diarrhea compared with 9.5% of patients receiving S. boulardii (p = 0.038). Risk factors found to be associated with AAD were multiple antibiotic combinations (containing clindamycin, cephalosporins, or trimethoprim-sulfamethoxazole) and tube feeding. Clostridium difficile, an anaerobe found in the stools of most patients with pseudomembranous colitis, was variably associated with AAD. We evaluated the role of C. difficile in AAD in the study population and found no significant association between the presence of C. difficile or cytotoxin with AAD. Approximately 33% of the patients without diarrhea harbored at least one C. difficile-positive stool and nearly 50% of these patients had detectable cytotoxin. Similar values were obtained in patients with diarrhea. Of C. difficile-positive patients, 31% (5/16) on placebo developed diarrhea compared with 9.4% (3/32) on S. boulardii; this difference was not statistically significant (p = 0.07). There were no discernable adverse effects of yeast administration. We conclude that S. boulardii reduces the incidence of antibiotic-associated diarrhea in hospitalized patients.

Adult↗

Treatment of recurrent Clostridium difficile colitis with vancomycin and Saccharomyces boulardii.

Recurrence of Clostridium difficile-associated diarrhea and pseudomembranous colitis occurs in up to 20% of patients after standard therapy. In these patients, subsequent recurrences are even more frequent. Saccharomyces boulardii, a nonpathogenic yeast, was found to be effective in preventing clindamycin cecitis recurrence in an animal model. We performed an open trial of S. boulardii to evaluate its efficacy in treating recurrences of C. difficile-associated colitis in humans. Thirteen patients with recurring C. difficile cytotoxin-positive diarrhea (who had an average of 3.6 previous recurrences) were treated with 10 days of vancomycin and a 30-day course of S. boulardii. Eleven (85%) had no further recurrences. S. boulardii may have a role in treating recurrent C. difficile diarrhea and colitis.

Antidiarrheals↗

Diffuse excess mucosal collagen in rectal biopsies facilitates differential diagnosis of solitary rectal ulcer syndrome from other inflammatory bowel diseases.

Solitary rectal ulcer syndrome (SRUS) is sufficiently uncommon that the clinician or general pathologist may lack familiarity with the disorder and may confuse it with other inflammatory bowel diseases. To evaluate the role of collagen staining in facilitating the differential diagnosis of SRUS, an initial open review was undertaken on 1672 consecutive patients whose 4780 colorectal biopsies were stained with H&E with added saffron to demonstrate collagen. Excess mucosal collagen was present in 39 (2.3%) of these patients. Twenty patients with a diffuse excess of mucosal collagen in biopsies from rectal ulcer margins or from otherwise abnormal rectal mucosa had SRUS; in the remaining 19 patients, excess mucosal collagen was focal (seven ischemic colitis, five collagenous colitis, three adenocarcinoma, and four chronic idiopathic ulcerative colitis). Diffuse excess mucosal collagen never was seen in idiopathic inflammatory bowel disease (128 Crohn's colitis and 446 ulcerative colitis). Blinded reviews then were performed on rectal biopsies from 33 patients with a variety of diagnoses (14 SRUS and 19 controls). Diffuse excess collagen by saffron staining was consistently observed in SRUS but was absent in all 19 controls. Additional blinded reviews were carried out because the collagen staining pattern in ischemic colitis, although focal, could potentially be confused with SRUS. It was possible to differentiate these two diseases blindly from one another by using additional histologic criteria (14 SRUS and 12 ischemic colitis). We conclude that the demonstration of a diffuse excess of mucosal collagen in rectal biopsies facilitates the diagnosis of SRUS and differentiates it from idiopathic ulcerative colitis and Crohn's disease, with which SRUS is often confused, and other inflammatory bowl diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗