OBJECTIVETo compare the intervention effects of four traditional Chinese medicines (TCMs) with typical cold or hot property on body temperature and temperature-sensitive transient receptor potential ion channel proteins (TRPs) of rats with yeast-induced fever.

METHODThe pyrexia model was induced by injecting yeast suspension subcutaneously. Totally 108 male SD rats were randomly divided into the normal group, the model group, the Rhei Radix et Rhizoma treated group, the Coptidis Rhizoma treated group, the Euodiae Fructus treated group, and the Alpiniae Officinarum Rhizoma treated group, with 18 rats in each group. At the 4 h, 8 h and 12 h after injection of yeast, the rats were sacrificed to collect their hypothalamus and dorsal root ganglion. The expressions of TRPV1 and TRPM8 were detected by immunohistochemistry and Western blot method.

RESULTCompared with the normal group, after injection of yeast, the temperature of rats in the model group notably increased, and reached the peak at 8 h (P < 0.01). The TRPV1 level in hypothalamus and dorsal root ganglia (DRG) of the model group significantly increased, whereas the TRPM8 level significantly reduced. Compared with the model group, the Rhei Radix et Rhizoma group and the Coptidis Rhizoma group showed significant decrease in the high body temperature of rats caused by yeast, down-regulation in the expression of TRPV1, and up-regulation in the expression of TRPM8 (P < 0.05 or P < 0.01). Euodiae Fructus and Alpiniae Officinarum Rhizoma had no significant effect on either temperature or TRPs of fever rats.

CONCLUSIONRhei Radix et Rhizoma and Coptidis Rhizoma, both are TCMs with cold property, can reduce the temperature of fever rats induced by yeast, which may be related to their effective regulation of TRPV1 and TRPM8 in hypothalamus and DRG, while Euodiae Fructus and Alpiniae Officinarum Rhizoma had no relevant effect.

Animals ; Antipyretics ; administration & dosage ; chemistry ; Body Temperature Regulation ; drug effects ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Fever ; drug therapy ; immunology ; microbiology ; physiopathology ; Gene Expression Regulation ; drug effects ; Humans ; Male ; Rats ; Rats, Sprague-Dawley ; Saccharomyces cerevisiae ; immunology ; TRPM Cation Channels ; genetics ; immunology ; TRPV Cation Channels ; genetics ; immunology

In order to discover the mechanism of Xuebijing oral effervescent tablet (XBJOET) to treat infectious diseases, the effect of XBJOET on endotoxin induced rabbit fever and disseminated intravascular coagulation (DIC) was investigated. Auricle microcirculation in rabbit was detected by laser speckle blood perfusion imager system; coagulation function was measured by coagulation analyzer, fibrinolytic system was quantified by Elisa assay and micro thrombosis in tissues was observed with HE staining under light microscope. The results demonstrated that the body temperature of rabbit decreased significantly at 1-3 h after administration with 4.8, 2.4 and 1.2 g x kg(-1) XBJOET to endotoxin induced DIC rabbit model, the auricle microcirculation blood flow in model group (54.45 +/- 14.53) PU was lower than that in control group (77.18 +/- 12.32) PU. The auricle microcirculation blood flow increased markedly and there was significant difference between model group and 1.2 g x kg(-1) XBJOET group. There was significant difference between model group and control group in the content of PAI1 and FIB. The PAI1 levels in model and control groups were (30.48 +/- 2.46) ng x mL(-1) and (20.93 +/- 3.25) ng x mL(-1), respectively. The FIB levels in model and control group were (3.34 +/- 1.09) g x L(-1) and (4.84 +/- 1.10) g x L(-1), respectively. The content of PAI1 in rabbit plasma decreased notably, there were significant differences between model group and 4.8, 2.4 g x kg(-1) XBJOET groups. On the contrary the content of FIB increased. XBJOET possessed pharmacological activities of curing infectious fever and DIC, the mechanism of which is related to amelioration of microcirculation disturbance, inhibition of fibrinolytic system activation and coagulation and micro thrombosis elimination.
Administration, Oral ; Animals ; Blood Coagulation ; drug effects ; Body Temperature ; drug effects ; Disseminated Intravascular Coagulation ; blood ; chemically induced ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Ear Auricle ; blood supply ; Endotoxins ; Female ; Fever ; chemically induced ; drug therapy ; physiopathology ; Fibrinogen ; metabolism ; Male ; Microcirculation ; Partial Thromboplastin Time ; Plasminogen Activator Inhibitor 1 ; blood ; Prothrombin Time ; Rabbits ; Tablets ; Thrombosis ; pathology

BACKGROUNDThe lowering of body temperature is a common, almost reflexive step in the daily care of septic shock patient. However, the effect of different magnitudes of fever control on the outcome of refractory septic patients with a very poor outcome is controversial and has yet to be explored.

METHODSThis prospective trial examined sixty-five refractory septic shock patients with a core temperature higher than 38.5°C. Patients were randomly assigned to a group achieving a "low temperature" range (LT group: 36.0 - 37.5°C) or to a group achieving a "high temperature" range (HT group: 37.5 - 38.3°C) by physical methods including a water-flow cooling blanket and ice packs. A target core temperature was achieved in 1 - 2 hours post-treatment, and maintained for 72 hours. Averaged values of core temperature as well as hemodynamic, respiratory, and laboratory variables were analyzed at baseline and during the first 72 hours after fever control.

RESULTSThirty-four (52.31%) patients were assigned to the LT group and thirty-one (47.69%) patients were assigned to the HT group. The mean core temperature was significantly lower in the LT group than in the HT group (36.61 vs. 37.85°C, respectively; P < 0.0001). The average heart rate (HR) (75.5 vs. 91.9 beats/min, respectively; P < 0.0001) and the mean cardiac output (CO) (5.35 vs. 6.45 L/min, respectively; P = 0.002) were also statistically significant lower in the LT group than in the HT group. The averaged serum lactate level was significantly higher in the LT group compared to the HT group (5.59 vs. 2.82 mmol/L, respectively; P = 0.008). Fibrinogen and activated partial thromboplatin time were also different between the two groups. The 28 days mortality was significantly higher in the LT group than in the HT group (61.8 vs. 25.8%, respectively; P = 0.003). A Cox-regression model analysis showed that mean core temperature during the 72 h period was an independent predictor of 28 days mortality (odds ratio (OR) = 0.42, 95%CI 0.25, 0.6; P = 0.001).

CONCLUSIONControlling fever to a lower range (36.0 - 37.5°C) may be harmful to patients with refractory septic shock by worsening tissue perfusion, compared to controlling it within a higher range (37.5 - 38.3°C). An understanding of the mechanisms responsible for these observations requires further investigation.

Adult ; Aged ; Aged, 80 and over ; Female ; Fever ; drug therapy ; physiopathology ; Humans ; Male ; Middle Aged ; Prospective Studies ; Shock, Septic ; drug therapy ; physiopathology ; Temperature ; Young Adult

INTRODUCTIONFebrile neutropenia (FN) remains a major cause of morbidity and mortality in Oncology/Haematology units. We launched a new protocol for FN management that incorporates risk stratification at our institute from October 2008. An audit was performed concurrently to evaluate the protocol and to define the epidemiology of FN locally.

MATERIALS AND METHODSCase records of all inpatients with FN between October 2008 and June 2009 were reviewed prospectively. Clinical and microbiological characteristics were collated along with outcomes and programme adherence. Statistical testing was performed using Stata 10.1.

RESULTSThere were 178 FN episodes (50 in patients with solid cancers) from 131 patients. Forty-two (23.6%) episodes were classified as high-risk according to MASCC criteria. Initial blood cultures were positive in 49 (27.5%) episodes, of which gram-negative bacilli (GNB) predominated. Overall compliance to the protocol was 56.7%, with the main issue being disinclination to use oral antibiotics as fi rst-line empirical therapy for low-risk episodes. Overall mortality was 7.3% and infection-related mortality was 4.5%. High-risk FN and the presence of central venous catheters were independently associated with bacteraemia on multivariate analysis, but there were no independent predictors of infection-related mortality.

CONCLUSIONSGNB accounted for the majority of bloodstream infections at our institute, unlike data from developed countries. Uptake of the new FN protocol was satisfactory, although the use of oral antibiotics as fi rst-line empirical therapy can be improved. A better method for predicting infections caused by antibiotic-resistant GNB is urgently required, and antibiotic resistance trends should be monitored to enable the implementation of more appropriate antibiotic regimens over time.

Adult ; Aged ; Aged, 80 and over ; Drug Resistance, Microbial ; Female ; Fever ; drug therapy ; physiopathology ; Gram-Negative Bacteria ; Hospitals, University ; Humans ; Male ; Medical Audit ; Middle Aged ; Neutropenia ; drug therapy ; physiopathology ; Outcome Assessment (Health Care) ; Prospective Studies ; Severity of Illness Index ; Singapore ; Young Adult

OBJECTIVETo study the antipyretic effect of baicalin in inhibiting yeast-induced fever in rats and the influence on inflammatory cytokine, then explore the possible mechanism of baicalin in inhibiting yeast-induced fever in rats.

METHODSRat modles of pyrexia were established by subcutaneous injection of yeast (2 g x kg(-1)); the rats of were divided into the normal control, model, baicalin high, medium and low-dose group and the effect of baicalin on the changes of the rats' temperature were observed. Dual antibody ELISA method was used to test the changes of IL-6, IL-1beta and TNF-alpha contents in in serum , hypothalamus and cerebral spinal fluid (CSF). Then analyze the correlation between the inhibition ratio of temperature heighten on three different dose of baicalin and the inhibition ratio of the contents heighten on IL-6, IL-1beta and TNF-alpha.

RESULTThe high dose of baicalin significantly inhibited the yeast-induced fever of rats, and decresesed IL-6, IL-1beta and TNF-alpha contents in serum, hypothalamus and CSF. The inhibition ratio of temperature heighten of baicalin had direct correlation with the inhibition ratio of the heighten on IL-1beta content in serum, hypothalamus and CSF (r = 0.873, P < 0.05), also dose TNF-alpha (r = 0.862, P < 0.01).

CONCLUSIONBaicalin may have obvious antipyretic effect by decreasing the increasing contents of IL-1beta and TNF-alpha in rats.

Animals ; Body Temperature ; drug effects ; Cytokines ; blood ; cerebrospinal fluid ; metabolism ; Fever ; blood ; cerebrospinal fluid ; drug therapy ; physiopathology ; Flavonoids ; pharmacology ; therapeutic use ; Hypothalamus ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Time Factors

Antitubercular Agents ; therapeutic use ; Child ; Child, Preschool ; Diagnostic Errors ; Female ; Fever ; etiology ; Humans ; Infant ; Male ; Pediatrics ; Tuberculosis ; drug therapy ; microbiology ; physiopathology ; X-Ray Film

This study examined the effect of experimentally induced fever on the pharmacokinetics of cefepime (75 mg/kg BW) administered intramuscularly to six rabbits. The study was carried out in two consecutive phases separated by a two-week washout period. An infection was induced by an intravenous inoculation of 5 x 10(8) colony-forming units of Escherichia coli 24 h before the pharmacokinetic investigation. A quantitative microbiological assay was employed to measure the plasma cefepime concentrations using an agar-gel diffusion method with Bacillus subtilis ATCC 6633 as the test organism. Twenty-four hour after the injection, the rectal temperature in the infected animals increased by 1degrees C. There was a significant reduction in the elimination halflife by 21.8% in the febrile rabbits compared to healthy animals. In addition, the infection significantly increased the peak plasma concentrations by 11.9%, the mean residence time by 19.9%, the area under the plasmaconcentration- time curve by 53.6% and the area under the moment curve by 62.3%. In conclusion, the endotoxin-induced febrile state produced significant changes in the plasma levels as well as some of the pharmacokinetic variables of cefepime in rabbits.
Animals ; Anti-Bacterial Agents/*administration&dosage/blood/*pharmacokinetics ; Area Under Curve ; Cephalosporins/*administration&dosage/blood/*pharmacokinetics ; Endotoxins/pharmacology ; Escherichia coli Infections/drug therapy/physiopathology ; Fever/chemically induced/*physiopathology ; Half-Life ; Injections, Intramuscular ; Male ; Rabbits

BACKGROUND: Amphotericin B dexoycholate is currently the standard empirical antifungal therapy for neutropenic patients with hematologic malignancies and who also have persistent fever that does not respond to antibacterial therapy. The antifungal triazoles offer a potentially safer and effective treatment alternative to Amphotericin B dexoycholate. METHODS: We assessed the efficacy and safety of intravenous itraconazole, as compared with the efficacy and safety of amphotericin B deoxycholate, as an empirical antifungal therapeutic agent in a matched case-control clinical trial from June 2004 to August 2005. RESULTS: Efficacy was evaluated in 96 patients (48 received itraconazole and 48 received amphotericin B deoxycholate) and all the patients who received the study drugs were evaluated for safety. The baseline demographic characteristics were well matched. The overall success rates were 47.9% for itraconazole and 43.8% for amphotericin B deoxycholate (% difference: 4.1 % [95% confidence interval for the difference: -15.8 to 24]), which fulfilled the statistical criteria for the non-inferiority of itraconazole. The proportions of patients who survived for at least seven days after discontinuation of therapy or who were prematurely discontinued from the study were not significantly different between the two groups. The rates of breakthrough fungal infections and resolution of fever during neutropenia were similar in both groups. More patients who received amphotericin B deoxycholate developed nephrotoxicity, hypokalemia or infusion-related events than did those patients who received itraconazole (nephrotoxicity: 16.7% vs. 1.8%, hypokalemia: 66.7% vs. 24.6%, and infusion-related events: 41.7% vs. 3.5%, respectively). CONCLUSIONS: Intravenous itraconazole is as effective as amphotericin B deoxycholate and it is generally better tolerated than amphotericin B deoxycholate when it is given as empirical antifungal therapy for Korean patients with persistent neutropenic fever.
Neutropenia/drug therapy/*physiopathology ; Male ; Itraconazole/*administration & dosage/therapeutic use ; Infusions, Intravenous ; Humans ; Hematologic Neoplasms/*drug therapy/physiopathology ; Fever/drug therapy/*physiopathology ; Female ; Chronic Disease ; Case-Control Studies ; Antifungal Agents/*administration & dosage/therapeutic use ; Amphotericin B/*administration & dosage/therapeutic use ; Adult

OBJECTIVEThe study was designed to investigate the clinical characteristics and the effects of therapeutic proposal on Kawasaki disease (KD).

METHODSClinical features, diagnosis and treatment for totally 942 patients with KD hospitalized during Jan, 2000 to Dec, 2004 were reviewed. Clinical features of typical and incomplete KD were compared. Also, influential factors for KD resistant to intravenous immune globulin (IVIG) therapy were analyzed. Five hundred and ten cases were followed up for analyzing the prognosis of coronary artery lesion (CAL).

RESULTS(1) 774 cases were diagnosed as typical KD, and 168 cases as incomplete KD. The incidence of infants with incomplete KD was higher than that of infants with typical KD (18.5% vs. 10.1%, P < 0.01). As compared with typical KD, the cases of incomplete KD had a long duration of fever before final diagnosis [(7.7 +/- 2.9) d vs. (7.0 +/- 2.4) d, P < 0.01], high hemoglobin level [Hb, (106.6 +/- 13.4) g/L vs. (103.5 +/- 12.3) g/L, P < 0.01], high hematocrit [Hct, (32.0 +/- 4.3)% vs. (31.0 +/- 4.0)%, P < 0.01], and high prevalence of CAL (23.8% vs. 16.8%, P < 0.05), respectively. The occurrence rate and emerging time of clinical manifestations in incomplete KD and in typical KD were presented, respectively: non-exudative conjunctivitis [occurrence rate, 64.9% vs. 93.5%; emerging time, (4.4 +/- 1.4) d vs. (4.0 +/- 1.6) d, respectively (P < 0.05 or P < 0.01)], erythema and cracking of lips [occurrence rate, 50.6% vs. 94.8%; emerging time, (4.9 +/- 1.4) d vs. (4.5 +/- 1.6) d, respectively (P < 0.05 or P < 0.01)], rash [occurrence rate, 35.1% vs. 87.7%; emerging time, (3.9 +/- 1.9) d vs. (3.4 +/- 1.7) d, respectively (P < 0.05 or P < 0.01)], erythema and edema of extremity [occurrence rate, 26.8% vs. 71.4%; emerging time, (6.7 +/- 1.5) d vs. (5.3 +/- 1.7) d, respectively (P < 0.01)], cervical lymphadenopathy [occurrence rate, 34.5% vs. 68.0%; emerging time, (4.3 +/- 2.5) d vs. (3.6 +/- 2.2) d, respectively (P < 0.05 or P < 0.01)], strawberry tongue [occurrence rate, 31.0% vs. 59.8%; emerging time, (5.6 +/- 2.2) d vs. (4.9 +/- 1.8) d, respectively (P < 0.05 or P < 0.01)], membranous desquamation of fingertips [occurrence rate, 34.5% vs. 56.3%; emerging time, (11.7 +/- 3.3) d vs. (10.3 +/- 2.7) d, respectively (P < 0.01)], and desquamation peri-anus [occurrence rate, 42.9% vs. 50.0%; emerging time, (6.7 +/- 2.7) d vs. (6.9 +/- 2.5) d, respectively (P > 0.05)]. Except for peri-anus desquamation, other clinical manifestations in incomplete KD were sporadical as compared to typical KD. (2) Six per cent (51/857) of cases were resistant to the IVIG therapy. As compared to the group responding to IVIG therapy, high prevalence of CAL (31.4% vs. 17.1%, P < 0.05), long fever duration [(10.6 +/- 3.9) d vs. (7.5 +/- 2.3) d, P < 0.01], low Hb level [(99.9 +/- 14.1) g/L vs. (104.3 +/- 12.4) g/L, P < 0.01], low Hct [(30.1 +/- 4.5)% vs. (31.2 +/- 4.0)%, P < 0.05], low platelet [PLT, (256.9 +/- 142.4) x 10(9)/L vs. (309.7 +/- 131.5) x 10(9)/L, P < 0.05], and low albumin level [ALB, (27.8 +/- 8.4) g/L vs. (33.5 +/- 6.7) g/L, P < 0.01] were found in the group resistant to IVIG therapy, respectively. (3) In patients who received IVIG 1 g/kg and 2 g/kg, the recovery rates from CAL were 83.1% and 89.7% (P > 0.05), respectively. The prevalence of CAL in those without CAL in acute and subacute stages was 0.9% and 3.5% (P > 0.05), respectively, during 2 year-follow-up period.

CONCLUSION(1) Infants appeared to have more chances to suffer from incomplete KD. Incomplete KD had high prevalence of CAL. The peri-anus desquamation might be an important clue for early diagnosis of incomplete KD. (2) In acute stage, the influential factors for KD resistance to IVIG therapy included prolonged fever, non-elevated PLT, and persistent decrease in Hb, Hct and ALB levels. (3) Children receiving IVIG 1 g/kg and 2 g/kg had the similar effects on recovery and prevention from CAL within the first two years after KD onset.

Adolescent ; Blood Platelets ; drug effects ; Child ; Child, Preschool ; China ; Coronary Aneurysm ; drug therapy ; epidemiology ; etiology ; prevention & control ; Coronary Artery Disease ; complications ; diagnosis ; drug therapy ; physiopathology ; Dose-Response Relationship, Drug ; Female ; Fever ; drug therapy ; physiopathology ; Follow-Up Studies ; Humans ; Immunoglobulins, Intravenous ; administration & dosage ; therapeutic use ; Immunologic Factors ; Infant ; Infant, Newborn ; Male ; Prognosis ; Retrospective Studies ; Risk Factors ; Treatment Outcome

Anticonvulsants ; therapeutic use ; Child ; Child, Preschool ; Diagnosis, Differential ; Electroencephalography ; Epilepsies, Myoclonic ; complications ; diagnosis ; drug therapy ; physiopathology ; Female ; Fever ; complications ; physiopathology ; Humans ; Infant ; Male ; Prognosis ; Seizures ; drug therapy ; etiology ; physiopathology ; Severity of Illness Index