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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An attractive approach to the treatment of inflammatory conditions such as osteo- and rheumatoid arthritis, inflammatory bowel disease, and sepsis is through the selective inhibition of human inducible nitric oxide synthase (hiNOS) since localized excess nitric oxide (NO) release has been implicated in the pathology of these diseases. A series of monosubstituted iminohomopiperidinium salts possessing lipophilic functionality at ring positions 3, 5, 6, and 7 has been synthesized, and series members have demonstrated the ability to inhibit the hiNOS isoform with an IC50 as low as 160 nM (7). Compounds were found that selectively inhibit hiNOS over the human endothelial constitutive enzyme (heNOS) with a heNOS/hiNOS IC50 ratio in excess of 100 and as high as 314 (9). Potencies for inhibition of hiNOS and the human neuronal constitutive enzyme (hnNOS) are comparable. Substitution in the 3 and 7 positions provides compounds that exhibit the greatest degree of selectivity for hiNOS and hnNOS over heNOS. Submicromolar potencies for 6 and 7 in a mouse RAW cell assay demonstrated the ability of these compounds to inhibit iNOS in a cellular environment. These latter compounds were also found to be orally bioavailable and efficacious due to their ability to inhibit the increase in plasma nitrite/nitrate levels in a rat LPS model.
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PMID:2-Iminohomopiperidinium salts as selective inhibitors of inducible nitric oxide synthase (iNOS). 955 68

The production of pro-inflammatory cytokines, such as interleukins 1 and 6 and tumour necrosis factors, occurs rapidly following trauma or invasion of the body by pathogenic organisms. The cytokines mediate the wide range of symptoms associated with trauma and infection, such as fever, anorexia, tissue wasting, acute phase protein production and immunomodulation. In part, the symptoms result from a co-ordinated response, in which the immune system is activated and nutrients released, from endogenous sources, to provide substrate for the immune system. Although the cytokine mediated response is an essential part of the response to trauma and infection, excessive production of pro-inflammatory cytokines, or production of cytokines in the wrong biological context, are associated with mortality and pathology in a wide range of diseases, such as malaria, sepsis, rheumatoid arthritis, inflammatory bowel disease, cancer and AIDS. Cytokine biology can be modulated by antiinflammatory drugs, recombinant cytokine receptor antagonists and nutrients. Among the nutrients, fats have a large potential for modulating cytokine biology. A number of trials have demonstrated the anti-inflammatory effects of fish oils, which are rich in n-3 polyunsaturated fatty acids, in rheumatoid arthritis, inflammatory bowel disease, psoriasis and asthma. Animal studies, conducted by ourselves and others, indicate that a range of fats can modulate pro-inflammatory cytokine production and actions. In summary fats rich in n-6 polyunsaturated fatty acids enhance IL1 production and tissue responsiveness to cytokines, fats rich in n-3 polyunsaturated fatty acids have the opposite effect, monounsaturated fatty acids decrease tissue responsiveness to cytokines and IL6 production is enhanced by total unsaturated fatty acid intake. There are a large number of potential cellular mechanisms which may mediate the effects observed. The majority relate to the ability of fats to alter the composition of membrane phospholipids. As a consequence of alterations in phospholipid composition, membrane fluidity may change, altering binding of cytokines to receptors and G protein activity. The nature of substrate for various signalling pathways associated with cytokine production and actions may also be changed. Consequently, alterations in eicosanoid production and activation of protein kinase C may occur. We have examined a number of these potential mechanisms in peritoneal macrophages of rats fed fats with a wide range of fatty acid composition. We have found that the total C18:2 and 20:4 diacyl species of phosphatidylethanolamine in peritoneal macrophages relates in a positive curvilinear fashion with dietary linoleic acid intake; that TNF induced IL1 and IL6 production relate in a positive curvilinear fashion to linoleic acid intake; that leukotriene B4 production relates positively with dietary linoleic acid intake over a range of moderate intakes and is suppressed at high intakes, while PGE2 production is enhanced. There was no clear relationship between linoleic acid intake and membrane fluidity, however fluidity was influenced in a complex manner by the type of fat in the diet, the period over which the fat was fed and the presence of absence of TNF stimulation. None of the proposed mechanisms, acting alone, can explain the positive effect of dietary linoleic acid intake on pro-inflammatory cytokine production. However each may be involved, in part, in the modulatory effects observed.
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PMID:Modulation of pro-inflammatory cytokine biology by unsaturated fatty acids. 955 30

Very little has been written concerning the use of laparoscopic techniques in inflammatory bowel disease. Its most useful indications appear to be in Crohn's disease, especially for intestinal diversions when severe perineal/perianal sepsis occurs. In this instance, avoidance of a laparotomy is a major advantage, and the simplicity of a laparoscopic stoma formation makes this a procedure that most surgeons may perform, even with minimal laparoscopic experience. Laparoscopic techniques may also be used for the limited resections required in Crohn's ileal or ileocolonic disease and for diagnostic purposes when indicated. The laparoscopic approach to the surgical treatment of ulcerative colitis (total abdominal colectomy, possibly with proctectomy and ileoanal pouch formation) remains to be evaluated before it can be contemplated as an alternative to conventional procedures.
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PMID:Laparoscopic Techniques for Inflammatory Bowel Disease. 1040 Oct 91

Intravenous cyclosporine therapy followed by oral cyclosporine therapy reduce the need for urgent surgery in steroid-refractory inflammatory bowel disease (IBD). Our objective is to report short- and long-term results of cyclosporine therapy in IBD patients. Thirteen patients with steroid-refractory IBD, seven patients with ulcerative colitis (UC), and six patients with Crohn's disease (CD) were treated with intravenous cyclosporine (4 mg/kg/day) for a mean period of 11.4+/-2.8 days (range, 4-15 days). Subsequently the patients were started on oral cyclosporine (8 mg/kg/day) and followed for a mean of 10.3+/-10 months (range, 1-30 months). Twelve patients responded to intravenous cyclosporine therapy. One patient with UC developed sepsis on the fourth day of intravenous cyclosporine therapy and needed urgent colectomy. Nine of 12 initial responders (6 patients with UC and 3 patients with CD) relapsed during follow-up despite oral cyclosporine and underwent elective surgery. One patient with CD relapsed 3 months after discontinuation of oral cyclosporine. Only two patients with CD are in long-term remission. There were no long-term side effects in any of the 13 treated patients. In conclusion, intravenous cyclosporine was effective in inducing remission or significant improvement in 12 of 13 patients with steroid-refractory IBD. However, with subsequent oral cyclosporine the remission could be maintained only for a short while. Each of the six patients with UC needed colectomy and three of the five patients with CD had intestinal resection within 12 months despite oral cyclosporine therapy.
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PMID:Cyclosporine therapy in inflammatory bowel disease: short-term and long-term results. 1047 68

The purpose of this study was to observe the prevalence of hypocholesterolaemia in a hospital population and also the causes and clinical outcome of this condition. Fifty-seven patients were found with a plasma cholesterol of < or = 3.0 mmol/L, which was less than 0.50% of all plasma cholesterol requests; there were 39 men and 18 women (P < 0.05, Chi-squared test). The mean age was 53.8 [21.3] (range 3-83 years). The mean plasma cholesterol concentration was 2.28 [0.56] mmol/L (1.16-3.0) and the mean triglyceride concentration was 1.58 [1.09] mmol/L (0.49-7.35). There was a significant correlation between plasma cholesterol concentration and plasma albumin (Rs = 0.48, P < 0.01) and between plasma total protein concentration (Rs = 0.49, P < 0.01). However, there was no relationship between the concentrations of plasma cholesterol and triglyceride (Rs = 0.10, P > 0.05). Eighteen per cent of patients with hypocholesterolaemia died during their hospitalization. Thirty-nine per cent of those who had a plasma cholesterol of < or = 2.0 mmol/L died whereas 71% of those who had a plasma cholesterol concentration of < 1.5 mmol/L died. Hypocholesterolaemia was more commonly seen in the intensive care unit and in post-operative patients, those with malignancy, sepsis, acute myocardial infarction, those who had inflammatory bowel disease and diabetics on insulin. Hypocholesterolaemia may be a useful predictor of mortality in hospital patients.
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PMID:Hypocholesterolaemia in a hospital population. 1050 11

In adults, toxic megacolon is a relatively uncommon but potentially lethal complication of inflammatory bowel disease (IBD), infectious colitis, or ischemic colitis caused by cancer chemotherapeutic agents. Patients have distension of the colon and signs of toxicity such as elevated temperature, hypotension, decreased level of consciousness and electrolyte imbalances. Factors thought to increase the risk include premature discontinuation of IBD medications; procedures that increase colon trauma, such as barium enema and colonoscopy; medications that decrease gastrointestinal motility; and electrolyte imbalances, especially hypokalemia. Differential diagnosis is made based on the patient's history and results of stool cultures and assay for Clostridium difficile toxin. Medical management in the intensive care unit includes careful monitoring, fluid volume and electrolyte replacement, bowel rest and decompression, antibiotic therapy, and cessation of medications that slow gastric motility. Surgical management may be necessary if there are signs of deterioration, perforation, hemorrhage, or sepsis.
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PMID:Toxic megacolon: diagnosis and treatment challenges. 1086 33

Inflammation is a complex reaction of the organism which develops as a response to invasion of an infectious subject or as a response to injury to cells or tissues. Correct and early localization of infection or an inflammatory lesion allows removing the inflammatory cause quickly. Over the recent thirty years, a wide range of radiopharmaceuticals, more or less applicable in scintigraphic imaging of inflammatory and infectious diseases, have been developed. The aim has been to develop new substances that are non-toxic, do not provoke immune reactions, and produce a minimal absorbed radioactive dose. Furthermore, these substances should accumulate significantly in the target tissue (i.e. in inflammation), while the accumulation in non-target tissues should be minimal or the elimination of radiopharmaceuticals from non-target tissues must be quick. The goal is that these substances may also be easily available and inexpensive. Another purpose is to develop such substances that could possess not only sufficient sensitivity but also specificity in relation to certain types of inflammation and infection. The main indications for radionuclide imaging are as follows: inflammatory bowel disease, soft tissue sepsis, predominantly abdominal sepsis, musculoskeletal infection, and fever of unknown origin.
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PMID:[A review of radiodiagnosis of inflammations]. 1124 30

Despite improvements in the supportive care of immunosuppressed patients controversy still surrounds the surgical management and outcome of anorectal sepsis in these patients. We reviewed 83 immunocompromised patients with diagnosis of perianal sepsis from 1995 to 1997. Sixty-six patients (80%) were followed for a mean of 15 months. Mean age was 44 years and 76 per cent were males. Twenty-eight per cent were HIV+, 34 per cent had inflammatory bowel disease on steroids, 20 per cent had malignancies, and 18 per cent had diabetes. Twenty-eight per cent had anal fistula, 2 per cent had perianal abscess, and 40 per cent had both. Primary sites of fistula were: transsphincteric (38%), intersphincteric (33%), superficial (20%), and suprasphincteric (3%), and multiple tracks (6%). Horseshoeing was present in 14 per cent of cases. The most commonly practiced surgical procedures were primary fistulotomy (n = 23) and fistulotomy plus drainage (n = 28). Seven patients underwent fistulotomy and ostomy and eight patients were treated with fistulectomy plus drainage. Most wounds (91%) healed within 8 weeks. Incontinence (6%) and recurrence (7%) were the most commonly observed complications. These results are similar to those seen in the general population. Perianal sepsis can be safely managed in immunocompromised patients, with high rates of healing and low complication rates. An aggressive sphincter-preserving approach in the management of these patients may be undertaken.
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PMID:Management of perianal sepsis in immunosuppressed patients. 1137 55

Patients with a wide variety of anorectal lesions present to family physicians. Most can be successfully managed in the office setting. A high index of suspicion for cancer should be maintained and all patients should be questioned about relevant family history or other indications for cancer screening. Patients with condylomata acuminata must be examined for human papillomavirus infection elsewhere after treatment of the presenting lesions. Their sexual partners should also be counseled and screened. Both surgical and nonsurgical treatments are available for the pain of anal fissure. Infection in the anorectal area may present as different types of abscesses, cryptitis, fistulae or perineal sepsis. Fistulae may result from localized infection or indicate inflammatory bowel disease. Protrusion of tissue through the anus may be due to hemorrhoids, mucosal prolapse, polyps or other lesions.
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PMID:Common anorectal conditions: Part II. Lesions. 1145 37

Patients with a wide variety of anorectal lesions present to family physicians. Most can be successfully managed in the office setting. A high index of suspicion for cancer should be maintained and all patients should be questioned about relevant family history or other indications for cancer screening. Patients with condylomata acuminata must be examined for human papillomavirus infection elsewhere after treatment of the presenting lesions. Their sexual partners should also be counseled and screened. Both surgical and nonsurgical treatments are available for the pain of anal fissure. Infection in the anorectal area may present as different types of abscesses, cryptitis, fistulae or perineal sepsis. Fistulae may result from localized infection or indicate inflammatory bowel disease. Protrusion of tissue through the anus may be due to hemorrhoids, mucosal prolapse, polyps or other lesions.
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PMID:Common anorectal conditions. 1175 66


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