chondroitin-sulfates and Acute-Disease

Topics: Acute Disease; Anticoagulants; Brain Ischemia; Chondroitin Sulfates; Databases, Factual; Dermatan Sulfate; Drug Combinations; Enoxaparin; Heparin; Heparin, Low-Molecular-Weight; Heparinoids; Heparitin Sulfate; Humans; Odds Ratio; Pulmonary Embolism; Randomized Controlled Trials as Topic; Stroke; Treatment Outcome; Venous Thrombosis

The numerous drugs to which the acutely ill are exposed place these patients at a significant risk of developing drug-induced thrombocytopenia. Such patients tend to have preexisting hemostatic defects that place them at additional risk of complications as a result of the drug-induced thrombocytopenia. The clinical challenge is to provide rapid identification and removal of the offending agent before clinically significant bleeding or, in the case of heparin, thrombosis results. Drug-induced thrombocytopenic disorders can be classified into three mechanisms: bone marrow suppression, immune-mediated destruction, and platelet aggregation. Clinical characteristics, preliminary laboratory findings, and drug history specific to the mechanisms can assist clinicians in rapidly isolating the causative drug.

Topics: Acute Disease; Anticoagulants; Antineoplastic Agents; Chondroitin Sulfates; Critical Care; Dermatan Sulfate; Disease Management; Drug Combinations; Fibrinolytic Agents; Heparitin Sulfate; Hirudin Therapy; Hirudins; Humans; Interleukin-11; Recombinant Proteins; Thrombocytopenia; Thrombopoietin

We studied the feasibility and efficacy of intravesical instillations with 40 ml chondroitin sulfate 0.2% solution to prevent or reduce acute radiation cystitis in women undergoing pelvic radiotherapy.. In a comparative pilot study in 20 patients, half of the patients received instillations. Instillations' bother was measured with visual analog scores (VAS, 0-10); bladder pain, with VAS; micturition-related quality of life, with the urogenital distress inventory (UDI).. One of the instilled patients discontinued the instillations. The first median "acceptability"-VAS was 0 (range, 0-3); the last median was 1 (range, 0-3). "Bladder pain"-VAS peaked halfway in the treatment among controls (median, 1; range, 0-5) and after treatment in the instilled patients (median, 1; range, 1-3). UDI scores showed over time median follow-up scores at or above median baseline scores in controls and at or below median baseline scores in instilled patients.. Intravesical instillations with chondroitin sulfate 0.2% solution may decrease the bother related to bladder symptoms and are well tolerated.

Topics: Acute Disease; Administration, Intravesical; Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Cystitis; Female; Humans; Middle Aged; Pain Measurement; Patient Acceptance of Health Care; Pilot Projects; Quality of Life; Radiation Injuries; Radiotherapy; Surveys and Questionnaires; Urination; Urination Disorders; Uterine Cervical Neoplasms; Uterine Neoplasms

To delineate the frequency, course, risk factors, and neuroanatomy of hemispatial neglect in a large stroke cohort.. One thousand two hundred eighty-one patients with acute stroke were enrolled in a multicenter trial of an anticoagulant. Presence and severity of neglect were assessed with the NIH Stroke Scale (NIHSS) neglect item, assessing tactile extinction and visuospatial neglect at entry, daily for 1 week, and at 3 months. Head CT scans were obtained on day 7, and infarct location and size were characterized.. Neglect was common at presentation, occurring in 43% of right brain-lesioned (RBL) patients and 20% of left brain-lesioned (LBL) patients (p < 0.001). At 3 months, neglect was present in 17% of RBL patients and in 5% of LBL patients (p < 0.001). In RBL patients, neglect was most frequently associated with lesions involving the (in descending order) temporal, parietal, frontal, occipital lobes, basal ganglia, and thalamus. Neglect was more common and persistent with cortical than with subcortical lesions. Increasing age was associated with increased risk of neglect in RBL patients, whereas gender and handedness did not significantly affect neglect frequency.. This series confirms that hemispatial neglect may occur with damage to several supratentorial structures but is most common and persistent with lesions of the right temporoparietal cortex. Increasing age is associated with neglect, particularly after right brain lesions. Gender and handedness do not exert a marked effect on the likelihood of the occurrence of neglect.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Basal Ganglia; Brain Ischemia; Cerebral Cortex; Cerebral Infarction; Chondroitin Sulfates; Cohort Studies; Dermatan Sulfate; Dominance, Cerebral; Double-Blind Method; Drug Combinations; Female; Heparitin Sulfate; Humans; Incidence; Male; Middle Aged; Perceptual Disorders; Risk Factors; Severity of Illness Index; Thalamus

The impact of early transcranial Doppler ultrasonography (TCD) upon stroke subtype diagnosis is unknown and may affect therapeutic strategies. In this study, the diagnostic usefulness of TCD in stroke subtype diagnosis according to the criteria of the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) study was investigated in patients with acute cerebral ischemia.. TCD examination within 24 h of symptom onset was performed in 50 consecutive patients with acute cerebral ischemia. Of these 54% were female. Sixty percent of patients were black, 36% white, and 4% Asian. Initial TOAST stroke subtype diagnosis (ITSSD) was based upon clinical presentation and initial brain imaging studies. Modified TOAST stroke subtype diagnosis was determined subsequently after additional review of the TCD examination. Final TOAST stroke subtype diagnosis was determined at hospital discharge, incorporating all diagnostic studies. Using final TOAST stroke subtype diagnosis as the 'gold standard' ITSSD and modified TOAST stroke subtype diagnosis were compared in order to determine additional benefit from the information obtained by TCD. Data were collected retrospectively by a single investigator.. ITSSD classified 23 of 50 (46%) patients correctly. After TCD, 30 of 50 (60%) patients were classified correctly, for an absolute benefit of 14% and a relative benefit of 30% (p = 0.018). Most benefit from TCD was observed in the TOAST stroke subtype category large-artery atherosclerosis, in particular in patients with intracranial vascular disease. In this category, ITSSD had a sensitivity of 27% which increased to 64% after TCD (p = 0.002).. TCD within 24 h of symptom onset improves the accuracy of early stroke subtype diagnosis in patients with acute cerebral ischemia due to large-artery atherosclerosis. This may have clinical implications for early therapeutic interventions.

Topics: Acute Disease; Aged; Antifibrinolytic Agents; Brain Ischemia; Cerebrovascular Circulation; Chondroitin Sulfates; Dermatan Sulfate; Female; Heparitin Sulfate; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Risk Factors; Tomography, X-Ray Computed; Ultrasonography, Doppler, Transcranial

In diabetic patients, wound healing is impaired. We studied the pathogenesis behind this clinical observation by characterizing the pattern of deposition of extracellular matrix (ECM) molecules and the cellular infiltrate in chronic (>8 wk) diabetic wounds, compared with chronic venous ulcers and an acute wound healing model. Punch biopsies were obtained from the chronic ulcer margins and control samples were collected from upper leg skin 5, 19, 28 d and 12 and 18 mo postwounding (p.w.). T cells, B cells, plasma cells, granulocytes and macrophages, and the ECM molecules fibronectin (FN), chondroitin sulfate (CS), and tenascin (TN) were visualized using immunohistochemical techniques. Expression of FN, CS, and TN was detected in dermal tissue early in normal wound healing (5-19 d p.w.). Abundant staining was seen 3 mo p.w., returning to prewounding levels after 12-18 mo p.w. In the dermis of chronic diabetic and venous ulcers with a duration of 12 mo or more, a prolonged presence of these ECM molecules was noted. Compared with normal wound healing: (i) the CD4/CD8 ratio in chronic wounds was significantly lower (p < 0.0027) due to a relatively lower number of CD4+ T cells; (ii) a significantly higher number of macrophages was present in the edge of both type of chronic ulcers (p < 0.001 versus day 29 p.w.); and (iii) more B cells and plasma cells were detected in both type of chronic wounds compared with any day in the acute wound healing model (p < 0.04 for CD20+ and p < 0.01 for CD79a+ cells). These data indicate that important differences exist in the cellular infiltrate and ECM expression patterns of acute, healing versus chronic wounds, which may be related to the nonhealing status of chronic wounds.

Topics: Acute Disease; Adult; Aged; Basement Membrane; CD4-CD8 Ratio; CD8-Positive T-Lymphocytes; Cell Count; Chondroitin Sulfates; Chronic Disease; Diabetes Mellitus, Type 1; Diabetic Foot; Extracellular Matrix; Female; Fibronectins; Granulocytes; Humans; Lymphocytes; Macrophages; Male; Middle Aged; Tenascin; Varicose Ulcer; Wound Healing; Wounds and Injuries

Identification of risk factors for bleeding and prospective evaluation of two bleeding risk scores in the treatment of acute venous thromboembolism.. Secondary analysis of a prospective, randomized, assessorblind, multicenter clinical trial.. One university and 2 regional teaching hospitals.. 188 patients treated with heparin or danaparoid for acute venous thromboembolism.. The presenting clinical features, the doses of the drugs, and the anticoagulant responses were analyzed using univariate and multivariate logistic regression analysis in order to evaluate prognostic factors for bleeding. In addition, the recently developed Utrecht bleeding risk score and Landefeld bleeding risk index were evaluated prospectively.. Major bleeding occurred in 4 patients (2.1%) and minor bleeding in 101 patients (53.7%). For all (major and minor combined) bleeding, body surface area < or = 2 m2 (odds ratio 2.3, 95% CI 1.2-4.4; p = 0.01), and malignancy (odds ratio 2.4, 95% CI 1.1-4.9; p = 0.02) were confirmed to be independent risk factors. An increased treatment-related risk of bleeding was observed in patients treated with high doses of heparin, independent of the concomitant activated partial thromboplastin time ratios. Both bleeding risk scores had low diagnostic value for bleeding in this sample of mainly minor bleeders.. A small body surface area and malignancy were associated with a higher frequency of bleeding. The bleeding risk scores merely offer the clinician a general estimation of the risk of bleeding. In patients with a small body surface area or in patients with malignancy, it may be of interest to study whether limited dose reduction of the anticoagulant drug may cause less bleeding without affecting efficacy.

Topics: Acenocoumarol; Acute Disease; Adult; Aged; Body Surface Area; Chondroitin Sulfates; Comorbidity; Dermatan Sulfate; Drug Combinations; Female; Fibrinolytic Agents; Hemorrhage; Heparin; Heparitin Sulfate; Humans; Male; Middle Aged; Neoplasms; Odds Ratio; Prospective Studies; Risk Factors; Single-Blind Method; Thromboembolism; Thrombolytic Therapy

To compare the relative safety and efficacy of a low-molecular-weight heparinoid (ORG 10172) with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke.. Double-blind randomized trial.. Seven Canadian university-affiliated hospitals.. Eighty-seven patients with acute ischemic stroke resulting in lower-limb paresis.. Patients received either low-molecular-weight heparinoid, 750 anti-factor Xa units twice daily, or unfractionated heparin, 5000 units subcutaneously twice daily. Treatment was continued for 14 days or until hospital discharge if sooner.. Deep vein thrombosis was diagnosed using 125I-labeled fibrinogen leg scanning and impedance plethysmography. Venography was indicated if either test was positive. Overt hemorrhage, major or minor, was assessed clinically.. Venous thrombosis occurred in four patients (9%) given low-molecular-weight heparinoid and in 13 patients (31%) given heparin (relative risk reduction, 71%; 95% CI, 16% to 93%. The corresponding rates for proximal vein thrombosis were 4% and 12%, respectively (relative risk reduction, 63%; P greater than 0.2). The incidence of hemorrhage was 2% in both groups.. Low-molecular-weight heparinoid, given in a fixed dose of 750 anti-factor Xa units subcutaneously twice daily, is more effective than subcutaneous low-dose heparin for the prevention of deep vein thrombosis in patients with acute ischemic stroke.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Antithrombin III; Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Double-Blind Method; Female; Fibrinolytic Agents; Follow-Up Studies; Glycosaminoglycans; Hemorrhage; Heparin; Heparitin Sulfate; Humans; Male; Middle Aged; Thrombophlebitis

In a double-blind, randomised trial Org 10172 low-molecular-weight (LMW) heparinoid was compared with placebo in the prevention of deep-vein thrombosis in patients with acute thrombotic stroke. Prophylaxis was started within 7 days of the onset of stroke with a loading dose of 1000 anti-factor-Xa units intravenously followed by a fixed dose of 750 anti-factor-Xa units twice a day subcutaneously; it was continued for 14 days or until hospital discharge, if earlier. 50 patients were randomised to receive Org 10172 and 25 to receive placebo. All patients underwent surveillance with I125-fibrinogen leg scanning and impedance plethysmography. Venography was carried out if either test became positive. Venous thrombosis occurred in 2 of 50 patients (4.0%) given Org 10172 and 7 of 25 patients (28.0%) given placebo (p = 0.005); the corresponding rates of proximal-vein thrombosis were 0% and 16%, respectively (p = 0.01). There was one major haemorrhage in the Org 10172 group and one minor bleed in the placebo group.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Cerebrovascular Disorders; Chondroitin Sulfates; Clinical Trials as Topic; Dermatan Sulfate; Female; Fibrinolytic Agents; Follow-Up Studies; Glycosaminoglycans; Heparin; Heparinoids; Heparitin Sulfate; Humans; Injections, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Radiography; Random Allocation; Thrombosis; Time Factors

There is a growing interest in therapies that may augment motor recovery that could be initiated in the acute stroke unit and maintained through the rehabilitation period. Homogenization of the currently fragmented stroke clinicometrics is necessary before such multidisciplinary trials can be conducted. The supplementary motor scale of the NIH Stroke Scale (SMS-NIHSS) is a simple and reliable scale for assessing proximal and distal motor function in the upper and lower extremities. We hypothesized that the currently underutilized SMS-NIHSS is a valid tool for assessing motor recovery with prognosticative value.. We performed an analysis of SMS-NIHSS scores recorded in 1,281 patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST). We plotted the probability of a favorable outcome (FO) and very favorable outcome (VFO) at 3 months based on the baseline SMS-NIHSS scores. In order to better study the relationship between SMS-NIHSS and 3-month functional outcome, we performed multivariate logistic regression analyses using both FO and VFO as outcome measures. Analyses were adjusted for potential confounders such as age, sex, side of the lesion, time from symptom onset to emergency room arrival, temperature, systolic blood pressure, blood glucose level and treatment group assignment (ORG 10172 vs. placebo). We also calculated the Spearman correlation coefficient between the SMS-NIHSS, Barthel Index (BI) and Glasgow Outcome Score (GOS) obtained at the 3-month visit.. The mean SMS-NIHSS scores were 8.18 at baseline and 4.68 at 3 months. The SMS-NIHSS scores showed a gradual improvement during the first 3 months after stroke. There was a linear relationship between the baseline SMS-NIHSS scores and the probability of an FO or VFO at 3 months. The SMS-NIHSS baseline score was an independent predictor of FO (OR = 0.86; 95% CI 0.84-0.87; p < 0.0001) and VFO (OR = 0.85; 95% CI 0.84-0.87; p < 0.0001) at 3 months after adjusting for confounders. The degree of improvement in the SMS-NIHSS scores from baseline to 3 months was also independently associated with FO and VFO (p < 0.0001). At 3 months, SMS-NIHSS scores showed a strong correlation with the BI (r = -0.70; p < 0.0001) and GOS (r = 0.73; p < 0.0001).. The SMS-NIHSS is a valid scale for assessing motor recovery with prognosticative value, and may be sensitive to changes during recovery. Given that the SMS-NIHSS is an extension of the widely accepted NIHSS, it could be easily implemented in trials conducted in a variety of clinical research settings, including acute stroke hospitals and rehabilitation units.

Topics: Acute Disease; Anticoagulants; Brain Damage, Chronic; Brain Ischemia; Chondroitin Sulfates; Clinical Trials as Topic; Confounding Factors, Epidemiologic; Dermatan Sulfate; Female; Glasgow Outcome Scale; Heparitin Sulfate; Humans; Male; Middle Aged; Motor Activity; Movement Disorders; Multicenter Studies as Topic; Prognosis; Recovery of Function; Retrospective Studies; Severity of Illness Index; Stroke; Stroke Rehabilitation; Treatment Outcome

Herbal and dietary supplements are widely used as measures to improve and preserve health and well-being. Among the bestselling preparations are dietary supplement containing glucosamine and chondroitine sulfate taken to improve symptoms of osteoarthritis.. We here present a case of a male patient with biopsy-proven acute and severe autoimmune hepatitis subsequent to intake of a preparation containing glucosamine and chondroitine sulfate. Response to steroids was favorable and resulted in complete remission of the patient. Diagnostic work-up of the case revealed no other possible cause of liver injury, and causality assessment using the Roussel Uclaf Causality Assessment Method (RUCAM) resulted in a possible causal relationship between intake of glucosamine and chondroitine sulfate and the adverse hepatic reaction.. The present case recalls that products containing glucosamine and chondroitine sulfate can occasionally cause acute liver injury mimicking autoimmune hepatitis, and reminds of the potential dangers of compounds with poor efficacy and ill-defined safety records.

Topics: Acute Disease; Aged; Chemical and Drug Induced Liver Injury; Chondroitin Sulfates; Diagnosis, Differential; Dietary Supplements; Glucosamine; Hepatitis, Autoimmune; Humans; Male

Lymphatic dysfunction in lymphedema results in chronic accumulation of interstitial fluid and life-long tissue swelling. In the absence of restored lymphatic drainage via adequate lymphangiogenesis, the interstitial environment can remodel in ways that decrease the elevated interstitial stress. Presently, relatively little is known about the glycosaminoglycans (GAGs) that become upregulated in the interstitium during lymphedema. We employed a mouse tail model of acute lymphedema that reproduces important features of the chronic human condition to establish a relationship between hyaluronan (HA) and sulfated GAG concentration with tissue swelling. We found that HA was upregulated by tissue injury at day 5 and became upregulated again by skin swelling (HA content increasing by 27% relative to controls at days 15 and 20). Surprisingly, the second phase of HA expression was associated with the declining phase of the tail skin swelling (tail diameter significantly decreasing by 17% from day 10 peak to day 20), demonstrating that HA is upregulated by tissue swelling and may help to counteract the edema in the mouse tail. This finding was confirmed by intradermal injection of an HA degrading enzyme (hyaluronidase) to the swollen tail, which was found to worsen the tail swelling. Sulfated GAGs, including chondroitin sulfate (CS), were not regulated by tissue swelling. The results demonstrate that HA, but not sulfated GAGs, is upregulated in the interstitium by acute tissue swelling. We speculate that HA expression during lymphedema may be part of a natural adaptive mechanism of the interstitial environment to reduce capillary filtration and increase interstitial fluid outflow following lymphatic obstruction and fluid accumulation.

Topics: Acute Disease; Animals; Chondroitin Sulfates; Disease Models, Animal; Glycosaminoglycans; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Lymphedema; Mice; Tail; Time Factors

Heat stroke is a condition characterized by high body temperature that can lead to hemorrhage and necrosis in multiple organs. Anticoagulants, such as danaparoid sodium (DA), inhibit various types of inflammation; however, the anti-inflammatory mechanism of action is not well understood. Given that heat stroke is a severe inflammatory response disease, we hypothesized that DA could inhibit inflammation from heat stress and prevent acute heat stroke.. Male Wistar rats were given a bolus injection of saline or DA (50 U/kg body weight) into the tail vein just prior to heat stress (42 °C for 30 min). Markers of inflammation were then determined in serum and tissue samples.. In rats pretreated with DA, induction of cytokines (interleukin [IL]-1β, IL-6, and tumor necrosis factor [TNF]-α), nitric oxide (NO), and high mobility group box 1 (HMGB1) protein were reduced compared with saline-treated rats. Histologic changes observed in lung, liver, and small intestine tissue samples of saline-treated rats were attenuated in DA-treated rats. Moreover, DA pretreatment improved survival in our rat model of heat stress-induced acute inflammation.. Collectively, our findings demonstrate that DA pretreatment may have value as a new therapeutic tool for heat stroke.

Topics: Acute Disease; Animals; Anticoagulants; Antithrombin III; Chondroitin Sulfates; Cytokines; Dermatan Sulfate; Disease Models, Animal; Fibrin Fibrinogen Degradation Products; Heat Exhaustion; Heat Stroke; Heparitin Sulfate; HMGB1 Protein; Inflammation; Intestine, Small; Liver; Lung; Male; Nitrates; Nitric Oxide; Nitrites; Peptide Hydrolases; Rats; Rats, Wistar; Survival Rate

In this study, we evaluated the utility of a dermal substitute for preserving maximal foot length after urgent surgical debridement. Patients referred to our Diabetic Foot Center with foot lesions were assessed for sensory-motor neuropathy, infection and critical limb ischaemia. The presence of acute foot infection indicated the need for immediate surgical debridement. The degree of amputation, if necessary, was based on the amount of apparently non infected vital tissue. When vital tendon/bone tissue remained exposed, the lesion was covered with a dermal substitute. From January to December 2008, 393 patients underwent surgical treatment for diabetic foot syndrome; 30 patients underwent immediate surgical debridement resulting in exposed tendon and/or bone tissues. An average of 4.4 +/- 2.1 days following surgical debridement, all 30 patients underwent dermal regeneration template grafting to cover-exposed healthy tendon and bone tissues, instead of achieving primary wound closure with a proximal amputation. After 21 days, a skin graft was performed. Complete wound healing occurred in 26 patients (86.7%). In these patients, the amputation level was significantly more distal (P < 0.003) with respect to that potentially required for immediate wound closure. The average healing time was 74.1 +/- 28.9 days. Four patients underwent a more proximal amputation. No patients underwent major amputation. The use of the dermal substitute for treating exposed tendon and bone tissues allowed timely wound healing and preserved maximal foot length. Continued follow-up will allow assessment of long-term relapse and complication rates. Such treatment could constitute part of the comprehensive management of diabetic wounds.

Topics: Acute Disease; Aged; Amputation, Surgical; Bacterial Infections; Chi-Square Distribution; Chondroitin Sulfates; Collagen; Debridement; Diabetic Foot; Emergencies; Female; Humans; Male; Retrospective Studies; Shoes; Skin Transplantation; Time Factors; Treatment Outcome; Wound Healing; Wound Infection

An 81-year-old woman was referred to our hospital with a diagnosis of acute cholangitis. Endoscopic retrograde cholangiography revealed a common bile duct (CBD) stone. In addition, CT showed thrombus of the right portal vein. Endoscopic sphincterotomy was performed to remove the CBD stone. Thrombosis was treated successfully with danaparoid sodium. It was speculated that the treatment of the acute cholangitis induced thrombolysis by the auto-fibrinolysis system and danaparoid sodium prevented the development of thrombus formation in this case.

Topics: Acute Disease; Aged, 80 and over; Anticoagulants; Cholangitis; Chondroitin Sulfates; Dermatan Sulfate; Female; Gallstones; Heparitin Sulfate; Humans; Portal Vein; Thrombosis

Reactive oxygen species (ROC) are the main causes of carbon tetrachloride (CCl4)-induced acute liver injury. Chondroitin-4-sulphate (C4S) is known to inhibit lipid peroxidation through antioxidant mechanisms. Activation of nuclear factor (NF)-kappaB and caspases may strongly intensify inflammation and cell damage, in addition to that directly exerted by ROS. We investigated whether treatment with C4S, besides exerting antioxidant activity, was able to modulate NF-kappaB and apoptosis activation in CCl4-induced liver injury in mice.. Acute hepatitis was induced in mice by an i.p. injection of CCl(4). Varying doses of C4S were administered i.p. 1 h before, 6 and 12 h after CCl4 injection. 24 h after CCl4 injection, the mice were killed for biochemical and histological analysis.. CCl4 injection produced: marked elevation of alanine aminotransferase and aspartate aminotransferase; hepatic membrane lipid peroxidation, assayed by 8-isoprostane levels; and depletion of reduced glutathione and superoxide dismutase. CCl4 also decreased NF-kappaB translocation and IkBalpha, and increased gene expression of mRNA and protein of metalloproteases (MMP)-2 and -9, and of pro- and cleaved forms of caspases-3 and -7. There was also increased liver polymorphonuclear infiltration, evaluated by elastase assay, and hepatic cell disruption.C4S treatment inhibited lipid peroxidation; blocked NF-kappaB activation and IkBalpha protein loss; decreased mRNA and proteins for MMPs and caspases; restored endogenous antioxidants; limited hepatic polymorphonuclear accumulation and tissue damage.. As antioxidants may inhibit NF-kappaB and caspase activation, we hypothesize that treatment with C4S was able to inhibit NF-kappaB and apoptosis activation in hepatic injury.

Topics: Acute Disease; Animals; Antioxidants; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Caspases; Chemical and Drug Induced Liver Injury; Chondroitin Sulfates; Enzyme Activation; Male; Mice; Mice, Inbred Strains; NF-kappa B; Random Allocation

Outcome measures in acute stroke trials are being refined. Changes in neurological deficits might be useful outcome measures because they can measure the entire spectrum of deficits.. We analyzed data from the acute stroke treatment trial Trial of Org 10172 in Acute Stroke Treatment (TOAST). Using logistic regression analysis, we modeled the probability of the TOAST predefined very favorable outcome (VFO; both Glasgow Outcome Scale 1 and modified Barthel Index 19 to 20) at 3 months. Within-subject changes (baseline-3 months) on the National Institutes of Health Stroke Scale (NIHSS) was the main predictor of interest.. The baseline median NIHSS for the entire TOAST cohort was 7, and it improved by 4 points (interquartile range 3 to 6) among 603 patient with VFO and by 2 points (interquartile range -1 to 5) among 638 patients without a VFO (P<0.001). The odds for VFO increased by 2.29 (95% CI, 2.06 to 2.54; P<0.001) for each 1-point improvement on the NIHSS. In receiver operating characteristic analysis, final NIHSS < or =2 was a good predictor of VFO, but no single NIHSS change cut point was a good predictor of VFO.. NIHSS change appears to be a useful outcome measure for acute stroke trials and is not fully comparable to dichotomized functional outcomes.

Topics: Acute Disease; Anticoagulants; Brain Ischemia; Chondroitin Sulfates; Clinical Trials as Topic; Cohort Studies; Data Interpretation, Statistical; Dermatan Sulfate; Heparitin Sulfate; Humans; National Institutes of Health (U.S.); Odds Ratio; Placebos; Regression Analysis; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Stroke; Treatment Outcome; United States

Wounds with large loss of deep tissue can be repaired using a dermis substitute. When wounds have an irregular fund, applying a skin graft on these one can be a failure. Integra Dermal Regeneration Template is a bilaminate material, a collagen chondroitin-sponge overlayed with silicone. It heals wounds where conventional methods of repair fail or are too risk. This study analizes Integra's use for chronic and pathological wounds in 7 patients. Applied to wounds reduces inflammation and protects it from a possible contamination or another injury. Imbibition, fibroblast migration, neovascularization, remodeling and maturation are distinct histologic phases of forming neodermis. Trough the silicon layer is possible to observe the histogenesis: the change in color of the matrix is a predictor of its vascularization. When the color has progressed from pink through pale yellow and finally to peach, the neodermis is fully vascolarized. The postoperative care is minimum. Integra is removed after three weeks regenerating a new dermal tissue. So it can be applied a thin skin graft until healing of all patients.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Chondroitin Sulfates; Chronic Disease; Collagen; Dermatologic Surgical Procedures; Female; Humans; Male; Middle Aged; Skin; Skin, Artificial; Wound Healing

Several reports have described a loss of endogenous antioxidants and molecular oxidative damage during acute pancreatitis. Since hyaluronic acid and chondroitin-4-sulfate possess antioxidant properties, the effect of the administration of these glycosaminoglycans in a cerulein-induced acute pancreatitis in rats was investigated. Cerulein administration produced pancreatic edema and a marked increase in serum lipase and amylase activity; induced a severe depletion of reduced glutathione, catalase, and superoxide dismutase levels; primed lipid peroxidation; and promoted neutrophil intervention. Intraperitoneal pretreatment of rats with hyaluronic acid or chondroitin-4-sulfate or with both compounds ameliorated pancreatic cell conditions; restored the endogenous antioxidants reduced glutathione, catalase and superoxide dismutase; limited cell membrane peroxidation; and reduced neutrophil activation. Our data confirm the antioxidant activity of these 2 glycosaminoglycans.

Topics: Acute Disease; Amylases; Animals; Antioxidants; Chondroitin Sulfates; Edema; Hyaluronic Acid; Lipase; Male; Pancreatitis; Peroxidase; Rats; Rats, Sprague-Dawley

We sought to improve the reliability of the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification of stroke subtype for retrospective use in clinical, health services, and quality of care outcome studies. The TOAST investigators devised a series of 11 definitions to classify patients with ischemic stroke into 5 major etiologic/pathophysiological groupings. Interrater agreement was reported to be substantial in a series of patients who were independently assessed by pairs of physicians. However, the investigators cautioned that disagreements in subtype assignment remain despite the use of these explicit criteria and that trials should include measures to ensure the most uniform diagnosis possible.. In preparation for a study of outcomes and management practices for patients with ischemic stroke within Department of Veterans Affairs hospitals, 2 neurologists and 2 internists first retrospectively classified a series of 14 randomly selected stroke patients on the basis of the TOAST definitions to provide a baseline assessment of interrater agreement. A 2-phase process was then used to improve the reliability of subtype assignment. In the first phase, a computerized algorithm was developed to assign the TOAST diagnostic category. The reliability of the computerized algorithm was tested with a series of synthetic cases designed to provide data fitting each of the 11 definitions. In the second phase, critical disagreements in the data abstraction process were identified and remaining variability was reduced by the development of standardized procedures for retrieving relevant information from the medical record.. The 4 physicians agreed in subtype diagnosis for only 2 of the 14 baseline cases (14%) using all 11 TOAST definitions and for 4 of the 14 cases (29%) when the classifications were collapsed into the 5 major etiologic/pathophysiological groupings (kappa=0.42; 95% CI, 0.32 to 0.53). There was 100% agreement between classifications generated by the computerized algorithm and the intended diagnostic groups for the 11 synthetic cases. The algorithm was then applied to the original 14 cases, and the diagnostic categorization was compared with each of the 4 physicians' baseline assignments. For the 5 collapsed subtypes, the algorithm-based and physician-assigned diagnoses disagreed for 29% to 50% of the cases, reflecting variation in the abstracted data and/or its interpretation. The use of an operations manual designed to guide data abstraction improved the reliability subtype assignment (kappa=0.54; 95% CI, 0.26 to 0.82). Critical disagreements in the abstracted data were identified, and the manual was revised accordingly. Reliability with the use of the 5 collapsed groupings then improved for both interrater (kappa=0.68; 95% CI, 0.44 to 0.91) and intrarater (kappa=0.74; 95% CI, 0.61 to 0.87) agreement. Examining each remaining disagreement revealed that half were due to ambiguities in the medical record and half were related to otherwise unexplained errors in data abstraction.. Ischemic stroke subtype based on published TOAST classification criteria can be reliably assigned with the use of a computerized algorithm with data obtained through standardized medical record abstraction procedures. Some variability in stroke subtype classification will remain because of inconsistencies in the medical record and errors in data abstraction. This residual variability can be addressed by having 2 raters classify each case and then identifying and resolving the reason(s) for the disagreement.

Topics: Acute Disease; Algorithms; Anticoagulants; Chondroitin Sulfates; Data Collection; Dermatan Sulfate; Diagnosis, Computer-Assisted; Drug Combinations; Heparitin Sulfate; Humans; Medical Records Systems, Computerized; Observer Variation; Reproducibility of Results; Retrospective Studies; Stroke

Early excision and prompt coverage in severely burned patients are the best way to lessen morbidity and improve survival. Repair of full-thickness burns requires replacement of both dermal and epidermal components of skin and treatment with split thickness autografts replaces both of them. But healthy skin is not sufficient in extensive burns. Alternative to split thickness skin grafts have been studied by several groups including epidermis, dermis or a complete replacement comprising epidermis and dermis. Because of the difficulties in homografts supplying, a new way was use to replace the dermis. In 1981, Yannas and Burke were the first to develop such a matrix. Intégra is available in France since 1997 and was used in our service for the treatment of both acute and reconstructive surgery for burned patients. Twenty patients were treated for acute surgery. Nineteen patients were treated for reconstructive surgery of burn scar contractures. Fifty-one grafts of Intégra were performed. Long-term final results seem to show that Intégra improve cosmetical and functional results and is a new surgical alternative for the treatment of burns in the acute phase as well as in late surgery of deformities.

Topics: Activities of Daily Living; Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Biocompatible Materials; Biopsy; Burns; Child; Chondroitin Sulfates; Collagen; Contracture; Female; Follow-Up Studies; France; Humans; Injury Severity Score; Male; Middle Aged; Plastic Surgery Procedures; Porosity; Skin Transplantation; Transplantation, Autologous; Transplantation, Homologous; Treatment Outcome; Wound Healing

1. Orbital accumulation of hydrophilic, interstitial glycosaminoglycans (GAGs) and subsequent expansion of retrobulbar tissue lead to the clinical manifestation of exophthalmos in patients with Graves' eye disease. 2. A highly specific method to determine the concentration and biochemical composition of different GAGs was developed in order to obtain a sensitive test system for the activity of the disease. By means of this method, GAG excretion in 24 h urine collections of 56 patients and 21 controls was analysed by precipitation with cetylpyridinium chloride and potassium acetate in ethanol, followed by sequential enzymic hydrolysis with chondroitin AC lyase, chondroitin ABC lyase and hyaluronate lyase, with HPLC analysis of the resulting alpha, beta-unsaturated disaccharides by anion-exchange chromatography. 3. Concentrations of GAG, chondroitin sulphate A (CA), dermatan sulphate (DS) and hyaluronic acid (HA) were determined in patients and controls, with high recovery rates [72.2 +/- 5.3%, mean +/- SEM; detection limit, 4.2 micrograms/l (0.01 mumol/l)], revealing marked differences in urinary concentrations of total GAG and HA, as well as an elevation of CA in patients compared with controls. 4. Method sensitivity was 0.86 for patients with active Graves' eye disease, and 0.87 for patients with untreated ophthalmopathy, whereas specificity was 1.0 for patients with inactive disease. Patients with increased GAG concentration responded well to steroids and/or orbital irradiation (before therapy: GAG, 111.49 +/- 40.32; CA, 59.58 +/- 21.34; DS, 25.05 +/- 8.12; HA, 26.88 +/- 11.63 mg/24 h; during therapy: GAG, 54.22 +/- 10.94; CA, 20.52 +/- 4.58; DS, 17.65 +/- 3.46; HA, 16.05 +/- 3.69 mg/24 h), whereas GAG excretion increased markedly 2-3 months after stopping prednisone therapy in patients with still active eye disease (GAG, 109.9 +/- 10.51; CA, 63.8 +/- 7.34; DS, 24.1 +/- 5.07; HA, 22.0 +/- 6.28 mg/24 h). 5. This sensitive method determines the nature of renally excreted GAGs, reflecting the aberrant synthesis pattern of fibroblasts in patients with Graves' disease.

Topics: Acute Disease; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Chondroitin Sulfates; Chromatography, High Pressure Liquid; Dermatan Sulfate; Female; Glycosaminoglycans; Graves Disease; Humans; Hyaluronic Acid; Male; Middle Aged; Prednisolone; Sensitivity and Specificity

Although standard heparin has been demonstrated to reduce endothelial cell dysfunction in acute ischemia-reperfusion injury, its mechanism of action remains unknown. We hypothesized that heparin's salutary endothelial effects are independent of its conventional anticoagulant activity and are not caused by nonspecific polyanion effects.. Isolated rat hindlimbs were perfused at constant pressure with an albumin-enriched crystalloid buffer. After 60 minutes of normothermic ischemia, endothelial function was assessed by measurement of endothelial-dependent vasodilation by log increment infusion of acetylcholine. Endothelial-independent vasodilation was measured by exposure to nitroprusside. Some groups were pretreated with heparinoids possessing minimal or intermediate anticoagulant activity.. Treatment with heparinoids with low anticoagulant activity significantly increased endothelial-dependent vasodilation when compared with the nontreated ischemic group and were statistically indistinguishable from the nonischemic control. Treatment with dextran sulfate, a randomly sulfated polymer with size and charge characteristics similar to heparin, did not change postischemic vasodilation. Endothelial-independent vasodilation was largely unaffected by ischemia-reperfusion or drug treatment.. A heparinoid with negligible antithrombin-binding activity (Astenose) attenuated postischemic endothelial dysfunction, suggesting that its mechanism of action was independent of anticoagulant activity. Failure of dextran sulfate to be protective implied that the effect was not caused by nonspecific polyanion action.

Topics: Acute Disease; Animals; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Dextran Sulfate; Endothelium, Vascular; Heparin; Heparitin Sulfate; Hindlimb; In Vitro Techniques; Ischemia; Male; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Vasodilation

Topics: Acute Disease; Brain Ischemia; Chondroitin Sulfates; Dermatan Sulfate; Fibrinolytic Agents; Glycosaminoglycans; Heparitin Sulfate; Humans; Randomized Controlled Trials as Topic

Topics: Acute Disease; Anterior Chamber; Cataract Extraction; Chondroitin; Chondroitin Sulfates; Choroid Hemorrhage; Drug Combinations; Humans; Hyaluronic Acid; Intraocular Pressure; Intraoperative Complications