Effects of miltefosine and other alkylphosphocholines on human intestinal parasite Entamoeba histolytica.
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The protozoan parasite Entamoeba histolytica is the cause of amoebic dysentery and liver abscess. It is therefore responsible for significant morbidity and mortality in a number of countries. Infections with E. histolytica are treated with nitroimidazoles, primarily with metronidazole. At this time, there is a lack of useful alternative classes of substances for the treatment of invasive amoebiasis. Alkylphosphocholines (alkyl-PCs) such as hexadecyl-PC (miltefosine) were originally developed as antitumor agents, but recently they have been successfully used for the treatment of visceral leishmaniasis in humans. We examined hexadecyl-PC and several other alkyl-PCs with longer alkyl chains, with and without double bond(s), for their activity against two strains of E. histolytica. The compounds with the highest activity were oleyl-PC, octadecyl-PC, and nonadecenyl-PC, with 50% effective concentrations for 48 h of treatment between 15 and 21 microM for strain SFL-3 and between 73 and 98 microM for strain HM-1:IMSS. We also tested liposomal formulations of these alkyl-PCs and miltefosine. The alkyl-PC liposomes showed slightly lower activity, but are expected to be well tolerated. Liposomal formulations of oleyl-PC or closely related alkyl-PCs could be promising candidates for testing as broad-spectrum antiprotozoal and antitumor agents in humans. (+info)
Flexible sigmoidoscopy.
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Flexible sigmoidoscopy remains a common tool used for the periodic screening of colorectal cancer. Most organizations recommend screening at three- to five-year intervals beginning at age 50 for persons with average risk. Extensive training in endoscopic maneuvering, colorectal anatomy and pathologic recognition is required. Most physicians report comfort performing the procedure unsupervised after 10 to 25 precepted sessions. The procedure involves the insertion of the sigmoidoscope through the anus and distal rectum and advancement of the scope tip to an average depth of 48 to 55 cm in the sigmoid colon. Once the sigmoidoscope has been appropriately advanced, the scope is slowly withdrawn, allowing for the inspection of colon mucosa during withdrawal. Polyps less than 5 mm in diameter should be biopsied. Polyps 5 to 10 mm or greater can be assumed to be adenomatous, and follow-up colonoscopy for complete polypectomy is required. Diverticulosis, hemorrhoids, nonspecific colitis and pseudomembranes may also be encountered during inspection. Use of preprocedural benzodiazepines can be helpful in reducing patient discomfort. 2001;63:1375-80,1383-4,1385-8.) (+info)
Characterization of AfaE adhesins produced by extraintestinal and intestinal human Escherichia coli isolates: PCR assays for detection of Afa adhesins that do or do not recognize Dr blood group antigens.
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Operons of the afa family are expressed by pathogenic Escherichia coli strains associated with intestinal and extraintestinal infections in humans and animals. The recently demonstrated heterogeneity of these operons (L. Lalioui, M. Jouve, P. Gounon, and C. Le Bouguenec, Infect. Immun. 67:5048-5059, 1999) was used to develop a new PCR assay for detecting all the operons of the afa family with a single genetic tool. This PCR approach was validated by investigating three collections of human E. coli isolates originating from the stools of infants with diarrhea (88 strains), the urine of patients with pyelonephritis (97 strains), and the blood of cancer patients (115 strains). The results obtained with this single test and those previously obtained with several PCR assays were closely correlated. The AfaE adhesins encoded by the afa operons are variable, particularly with respect to the primary sequence encoded by the afaE gene. The receptor binding specificities have not been determined for all of these adhesins; some recognize the Dr blood group antigen (Afa/Dr(+) adhesins) on the human decay-accelerating factor (DAF) as a receptor, and others (Afa/Dr(-) adhesins) do not. Thus, the afa operons detected in this study were characterized by subtyping the afaE gene using specific PCRs. In addition, the DAF-binding capacities of as-yet-uncharacterized AfaE adhesins were tested by various cellular approaches. The afaE8 subtype (Afa/Dr(-) adhesin) was found to predominate in afa-positive isolates from sepsis patients (75%); it was frequent in afa-positive pyelonephritis E. coli (55.5%) and absent from diarrhea-associated strains. In contrast, Afa/Dr(+) strains (regardless of the afaE subtype) were associated with both diarrhea (100%) and extraintestinal infections (44 and 25% in afa-positive pyelonephritis and sepsis strains, respectively). These data suggest that there is an association between the subtype of AfaE adhesin and the physiological site of the infection caused by afa-positive strains. (+info)
Co-administration of the health food supplement, bovine colostrum, reduces the acute non-steroidal anti-inflammatory drug-induced increase in intestinal permeability.
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Non-steroidal anti-inflammatory drugs (NSAIDs) are effective analgesics but cause gastrointestinal injury. Present prophylactic measures are suboptimal and novel therapies are required. Bovine colostrum is a cheap, readily available source of growth factors, which reduces gastrointestinal injury in rats and mice. We therefore examined whether spray-dried, defatted colostrum could reduce the rise in gut permeability (a non-invasive marker of intestinal injury) caused by NSAIDs in volunteers and patients taking NSAIDs for clinical reasons. Healthy male volunteers (n=7) participated in a randomized crossover trial comparing changes in gut permeability (lactulose/rhamnose ratios) before and after 5 days of 50 mg of indomethacin three times daily (tds) per oral with colostrum (125 ml, tds) or whey protein (control) co-administration. A second study examined the effect of colostral and control solutions (125 ml, tds for 7 days) on gut permeability in patients (n=15) taking a substantial, regular dose of an NSAID for clinical reasons. For both studies, there was a 2 week washout period between treatment arms. In volunteers, indomethacin caused a 3-fold increase in gut permeability in the control arm (lactulose/rhamnose ratio 0.36+/-0.07 prior to indomethacin and 1.17+/-0.25 on day 5, P<0.01), whereas no significant increase in permeability was seen when colostrum was co-administered. In patients taking long-term NSAID treatment, initial permeability ratios were low (0.13+/-0.02), despite continuing on the drug, and permeability was not influenced by co-administration of test solutions. These studies provide preliminary evidence that bovine colostrum, which is already currently available as an over-the-counter preparation, may provide a novel approach to the prevention of NSAID-induced gastrointestinal damage in humans. (+info)
Experimental evidence suggesting that nitric oxide diffuses from tissue into blood but not from blood into tissue.
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The aim of this study was to evaluate in vivo whether nitric oxide (NO) is able to diffuse from blood into tissues and vice versa from tissues into blood. We used an in vivo model of intestinal ischemia (superior mesenteric artery occlusion) selectively increasing NO levels in intestinal tissue and an infusion of L-arginine selectively increasing NO levels in blood. In this model we followed formation of nitrosyl complexes of hemoglobin (Hb-NO) in blood and nitrosyl-diethyldithiocarbamate-iron complexes (DETC--Fe--NO) in ischemic intestine and normoxic tissues by means of electron paramagnetic resonance spectroscopy. NO trapping by DETC--Fe in the tissues resulted in a reduction of Hb--NO levels in blood accompanied by the formation of water-insoluble DETC--Fe-NO complexes in ischemic intestine and normoxic tissues both during ischemia and during reperfusion. Administration of L-arginine increased NO levels in blood but neither in ischemic intestine nor in normoxic tissue. Our data suggest that NO released in blood from endothelial cells does not diffuse into tissue. In contrast, NO formed in tissue diffuses into blood. The latter indicates that NO formed in tissues may exert its biological activities systematically. (+info)
Surgical management of thrombotic acute intestinal ischemia.
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OBJECTIVE: To evaluate the University of Kentucky experience in treating acute intestinal ischemia to elucidate factors that contribute to survival. SUMMARY BACKGROUND DATA: Acute intestinal ischemia is reported to have a poor prognosis, with survival rates ranging from 0% to 40%. This is based on several reports, most of which were published more than a decade ago. Remarkably, there is a paucity of recent studies that report on current outcome for acute mesenteric ischemia. METHODS: A comparative retrospective analysis was performed on patients who were diagnosed with acute intestinal ischemia between May 1993 and July 2000. Patients were divided into two cohorts: nonthrombotic and thrombotic causes. The latter cohort was subdivided into three etiologic subsets: arterial embolism, arterial thrombosis, and venous thrombosis. Patient demographics, clinical characteristics, risk factors, surgical procedures, and survival were analyzed. Survival was compared with a collated historical series. RESULTS: Acute intestinal ischemia was diagnosed in 170 patients. The etiologies were nonthrombotic (102/170, 60%), thrombotic (58/170, 34%), or indeterminate (10/170, 6%). In the thrombotic cohort, arterial embolism accounted for 38% (22/58) of the cases, arterial thrombosis for 36% (21/58), and venous thrombosis for 26% (15/58). Patients with venous thrombosis were younger. Venous thrombosis was observed more often in men; arterial thrombosis was more frequent in women. The survival rate was 87% in the venous thrombosis group versus 41% and 38% for arterial embolism and thrombosis, respectively. Compared with the collated historical series, the survival rate was 52% versus 25%. CONCLUSIONS: These results indicate that the prognosis for patients with acute intestinal ischemia is substantially better than previously reported. (+info)
Colorectal patients and cardiac arrhythmias detected on the surgical high dependency unit.
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INTRODUCTION: Surgical high dependency unit (SHDU) care is becoming an integral feature of colorectal surgical practice. Routine ECG monitoring is a feature of surgical care in this setting. The aim of this study was to determine the incidence and outcome of cardiac arrhythmias detected in an SHDU population of colorectal patients. PATIENTS AND METHODS: 226 patients over a 12 month period were admitted to a 6-bedded SHDU under the care of 3 colorectal surgeons. A total of 29 patients (13%) had significant arrhythmias on ECG monitoring (median age 74 years, range 35-88 years). Pre-existing ischaemic heart disease was present in 9 patients--colorectal cancer and inflammatory bowel disease accounted for the underlying problem in the majority of these patients. RESULTS: Equal numbers of supraventricular and ventricular arrhythmias were detected--atrial fibrillation being the most commonly detected abnormality. Therapeutic intervention (electrolyte correction and anti-arrhythmic agents) was required in 23 patients. One patient required DC shock for ventricular fibrillation. Seven patients were transferred to the heart care unit or intensive care unit to manage their cardiac problems. Two patients died as a result of their cardiac problem, 27 were discharged home alive--3 on long-term anti-arrhythmic therapy. CONCLUSIONS: The postoperative environment of colorectal patients has been radically altered by the introduction of the SHDU. If colorectal surgeons are to remain central to the postoperative care of their patients, all surgical staff will require training in the recognition and protocol prevention and management of cardiac arrhythmias. Certification of colorectal surgeons in advanced life support is more relevant to colorectal surgery than certification in trauma care. (+info)
Diverticular disease of the large intestine in Northern Norway.
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In 280 unselected necropsies on patients over 20 years of age in Northern Norway, diverticular disease was present in 25% of the males and 43% of the females. The frequency of diverticular disease increased in both sexes by age. Both the frequency of diverticular disease and the average number of diverticula per case with diverticular disease were higher in females than in males in all age groups. The sigmoid was the most frequent site of diverticula in both sexes and for all ages, and the average number of diverticula per diverticulum-bearing segment was also highest in the sigmoid for all ages and in both sexes. The average number of diverticula in the sigmoid of affected individuals increased with age and with the number of segments involved. Diverticular disease was not associated with adenomas of the large intestine or with malignant or benign neoplasms elsewhere in the body or with any of the common diseases thought to be related to a Western type of diet, except with cerebrovascular disease. (+info)