Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cefozopran (CZOP) was administered via intravenous injection to 9 patients (ages ranging from 1 month to 13 years) with pediatric bacterial infections, at daily dose levels between 56.7 and 200 mg/kg, divided into 3 or 4 doses. The following results were obtained. 1. Eight patients, including 1 with purulent meningitis, 1 with sepsis, 3 with acute pneumonia and 3 with lymphadenitis, were treated and subjected to clinical evaluation. Clinical effects were excellent in 6 cases and good in 2, with an overall efficacy rate of 100%. One case with pyoderma was not evaluated because of a combined use of an external antibiotic. 2. Organisms suspected as pathogens included 5 strains: 3 strains of Haemophilus influenzae, 1 strain of Staphylococcus aureus and 1 of Escherichia coli. Bacteriologically, all the strains were eradicated. 3. Side effects or abnormal laboratory test results were observed in 4 cases; wheal in 1 case, elevated GOT and GPT in 2 cases and eosinophilia in 1 case. 4. From the results described above, we considered that CZOP would be an effective drug for use in pediatric bacterial infections.
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PMID:[Clinical studies on cefozopran in pediatrics]. 785 86

We studied the clinical efficacy of biapenem (L-627), a new parenteral carbapenem beta-lactam antibiotic in the pediatric field. L-627 was administered intravenously to 11 patients with ages ranging 2 months to 10 years and 5 months with acute infectious diseases. Doses ranged 28.1 to 72.6 mg/kg/day. The diagnosed diseases included 7 respiratory tract infections, 1 purulent meningitis, 1 sepsis, 1 cervical lymphadenitis and 1 urinary tract infection. Two of these cases one with Mycoplasma infection and the other which had been administered with other antimicrobial agents were not evaluated. The clinical efficacy rate was 77.8% (7/9) and the bacteriological eradication rate was 66.7% (4/6). Laboratory examinations revealed that there was one case with elevated liver enzyme levels with showing elevation of GOT, GPT and LDH. No other side effects attributable to this drug were observed. Thus, it appears that L-627 is a useful antibiotic in treating moderate to severe acute bacterial infections in children.
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PMID:[Clinical evaluation of biapenem (L-627), a new carbapenem antibiotic in the pediatric field]. 793 26

We investigated the clinical efficacy of arbekacin (ABK) in patients with methicillin-resistant Staphylococcus aureus (MRSA) infections, and also studied coagulase types, beta-lactamase producing activity and drug sensitivity of MRSA isolated from various clinical specimens. A total of 23 patients with MRSA infections (13 cases of pneumonia, 1 case of sepsis, 1 case of pneumonia and sepsis and 8 cases of the others) who were hospitalized from April 1992 to September 1993 were enrolled in this study. They were 14 males and 9 females, and the mean age was 66.9 years (range, 18-91 years). All patients had underlying diseases (mainly malignant tumors and cerebrovascular diseases). ABK was given intravenously at doses ranging from 75 to 100 mg twice daily. The clinical efficacy rate was 90%; 8 cases showed excellent responses, 10 cases good, 1 case fair, 1 case poor and 3 cases were unevaluable. The eradication rate of MRSA was 81.8%; 16 cases were judged as eradicated, 3 cases decreased, 2 cases replaced, 1 case unchanged and in 1 case the bacteriological response was unknown. Side effects were not observed, but S-GPT was elevated in 1 case. Coagulase types of MRSA (123 strains) isolated at the institutes involved in the study were type II (56 strains), type IV (12 strains), type VII (13 strains) and other types (2 strains), but coagulase types of 40 strains could not be determined. Eighty-four strains (68.3%) produced beta-lactamases. MICs of ABK were 0.5 microgram/ml against 43 strains and 1 microgram/ml against 37 strains, and all of the MICs were under 4 micrograms/ml. In summary, ABK showed high antimicrobial activity against MRSA and clinical usefulness in the infections investigated.
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PMID:[Clinical efficacy of arbekacin in patients with methicillin-resistant Staphylococcus aureus infections. Research Group of MRSA Forum]. 807 80

The efficacy, safety and usefulness of murine anti-endotoxin monoclonal IgM antibody "E5, an intravenous dose of 2 mg/kg" were evaluated in 88 patients with suspected Gram-negative sepsis from 37 institutes in Japan. Out of these, 74 patients were evaluable for the efficacy, 85 for safety and 75 for clinical usefulness. In assessing the efficacy, the patients were divided into 3 groups based on the plasma endotoxin levels (Endospecy with new PCA treatment of plasma): H group with a level of above 9.8 pg/ml and M group with a level of 3.0-9.8 pg/ml and L group with a level of below 3.0 pg/ml. 1. The efficacy rates as assessed following administration of E5 were 73.1% in the H group, 70.4% in the M group and 38.1% in the L group being higher in the groups with significantly high plasma endotoxin levels. 2. In both the H and M groups in whom plasma endotoxin levels were significantly high, the majority of the patients showed rapid reduction of the levels after administration of E5. 3. In all groups, improvement in body temperature, pulse rate, blood TNF-alpha and blood IL-6 was observed after treatment with E5. In the H and M groups with an endotoxin level of > or = 3.0 pg/ml, improvement in platelet count as well as in CRP was noted. The H group showed also improvement in WBC. 4. Improvement in the shock score was noted in all the groups but was more outstanding in the H and M groups in the early stage of treatment. 5. Side effects were seen in 5 (5.9%) of 85 patients and all thought to be allergic in symptoms such as rash, itching, fever and flare. 6. The reaction to the prick test performed before administration of E5 was negative in all these 5 patients. For 3 of the 5 patients, anti-E5 IgE antibody was measured. In all of them, the IgE levels were higher than those of healthy controls. Also, in 47.6% of patients, an elevation of anti-E5 IgG antibody was noted two weeks after the administration. 7. Clinical laboratory abnormalities were observed in 3 (3.5%) of 85 patients. They were an elevation of S-GOT.S-GPT and lowering of BUN, increased Al-p and decreased CH50, increased neutrophilia (%) and were all slight in the degree of the changes. 8. The clinical usefulness of E5 was evaluated for 75 patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Phase II study of edobacomab (E5) in the treatment of gram-negative sepsis]. 813 82

Following its introduction into the market, PAPM/BP (panipenem/betamipron) was clinically studied in 188 evaluable cases out of 207 cases primarily of respiratory infectious diseases treated at the pediatric departments of 15 hospitals. In the clinical evaluation, the drug proved effective in three of three cases of sepsis; three of three cases of suppurative meningitis; nine of ten cases of laryngopharyngitis, six of seven cases of tonsillitis, 56 of 63 cases of acute bronchitis, 90 of 98 cases of pneumonia, and one of one case of phyothorax, all of which are respiratory infectious diseases; one of one case of secondary infection of a chronic respiratory disease; and two of two cases of lymphadenitis, which is a disease of the soft dermal structure. The overall efficacy rate was 91.0% (171/188 cases). In the bacteriological study, Gram-positive bacteria were eliminated in five of five strains of S. aureus, 30 of 31 strains of S. pneumoniae (96.8%), and three of three strains of S. pyogenes. Gramnegative bacteria were eliminated in 15 of 17 strains of H. influenzae (88.2%), three of four strains of M. catarrhalis, and two of two strains of K. pneumoniae. The overall elimination rate was 92.1% (70/76 strains). In the 23 strains of S. pneumoniae that were examined, penicillin-resistant strains accounted for 56.5%, showing an elimination rate of 100%. No serious adverse effects were observed, and the incidence of adverse effects was 1.45%. As for abnormalities in laboratory tests, levels of GOT and GPT increased in eight cases (3.88%), LDH increased in one case (0.48%), and neutropenia occurred in one case (0.51%). These results suggest that PAMP/BP could be considered the first choice in the treatment of infectious diseases in pediatrics, due to its effectiveness and high level of safety.
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PMID:[Clinical and bacteriological studies on panipenem/betamipron in pediatrics. Kanagawa Research Group for Infectious Diseases of Children]. 964 2

We report a 61-year-old Japanese man who died of complications of esophagus cancer surgery. He was well until his 55 years of the age, when he had an onset of speech disturbance and hand writing. He was seen by a neurologist who prescribed Menesit 600 mg/day. His symptoms improved with this medication. In 1993, three years after the onset, he started to show gait disturbance and easy to fall. In 1995, he noted difficulty in eye opening. He visited our clinic on October 26, 1996. On examination, he showed vertical gaze paresis, masked face, nuchal rigidity, small step gait, freezing phenomena, and festination. His mental status was normal. He was treated with 800 mg/day of Menesit, 800 mg/day of L-dops, and 10 mg/day of bromocriptine with little improvement in his symptoms. Cranial CT scan revealed some dilatation of the third ventricle. Subsequent clinical course was one of the slow progression of his parkinsonism. In September of 1997, he noted difficulty in swallowing. He was admitted to the gastrointestinal service of our hospital on October 14, 1997. On admission, neurologic status was essentially similar to the previous one, but he showed more advanced state of his parkinsonism. Upper gastrointestinal series revealed a mass lesion of about 11.5 cm in length protruding into the lower esophagus lumen. Subtotal esophagus resection including the mass was performed on December 2, 1997. The stomach was elevated for anastomosis with the upper esophagus. No metastases were found in the mediastinum except for two lymph nodes in the para-esophageal region. The subsequent course was complicated by marked elevation of GOT, GPT, LDH, total bilirubin as well as direct bilirubin, alkaliphosphatase, and amylase starting in the evening of the surgery. On December 7, leukocytosis and pneumonic shadow were seen involving his right lung. On December 10, he developed cardiopulmonary arrest. He was once resuscitated; however, he developed cardiac arrest again seven hours later and pronounced dead. He was discussed in a neurologic CPC. The chief discussant arrived at the conclusion that the patient had PSP and the cause of the death was ascribed to circulatory disturbance to the liver. The discussant also thought that the terminal course was complicated by cholangitis or cholecystitis, sepsis, and pulmonary embolism. Surgical specimen of the esophagus tumor revealed carcinosarcoma. Postmortem examination revealed yellowish discoloration of the peritoneum and mesenterium, and accumulation of clouded ascites indicating the presence of peritonitis. Inflammatory change extended to the mediastinum. On microscopic examination, various kinds of bacilli and candida spores were seen. The liver was enlarged and a perforation was noted in the gallbladder causing biliary necrosis in the adjacent liver. An extensive infarct was seen in the left lobe of the liver; this was found to be due to obstruction of the hepatic artery at the site of the duodenohepatic mesenterium and obstruction of intrahepatic portal vein secondary to retrograde intrahepatic cholangitis in the left lobe. A piece of surgical threads was seen adjacent to the hepatic artery; foreign body granulomatous reaction was seen surrounding the surgical thread. The rupture of the gallbladder appeared to be due to the obstruction of the left branch of the hepatic artery. Neuropathologic examination revealed extensive degeneration of the pallidum, the substantia nigra, and the subthalamic nucleus and presence of neurofibrillary tangles in the remaining neurons. The neuropathologic findings were consistent with progressive supranuclear palsy, although the pathologic changes in the midbrain tegmentum was only mild gliosis.
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PMID:[A 61-year-old man with progressive gait disturbance, freezing, and vertical gaze paresis who developed esophagus cancer]. 986 33

Pharmacokinetics, clinical efficacy and safety of teicoplanin (TEIC) were evaluated in pediatric and neonate patients with MRSA sepsis in the dosages approved in overseas. The administrated dose for pediatrics patients was 10 mg/kg once at hour 0, 12 and 24, followed by every 24 hours intervals. In neonates patients, first dose was 16 mg/kg, then 8 mg/kg every 24 hours intervals. 1. Pharmacokinetic results. All 17 patients (9 neonates and 8 pediatrics) who received TEIC were evaluated for pharmacokinetics. Trough concentrations were analyzed in 16 patients (9 neonates and 7 pediatrics) excluding one patient for lack of measurement of drug concentration at day 7. No patient with a concentration exceeding 60 micrograms/mL in peak or trough concentrations were reported. Mean concentrations in trough at day 3, 4 and 7 in neonates were 15.2, 14.7 and 17.8 micrograms/mL, and in pediatrics were 12.5, 12.2 and 13.1 micrograms/mL, respectively. These results were similar to those reported in foreign pediatrics and neonates patients. 2. Efficacy and safety results. Since no patient was excluded, all patients were evaluated for efficacy and safety. Microbiological efficacy as well as clinical cure were secondarily evaluated in 2 patients for whom MRSA was isolated from blood. Clinical efficacy rate was 76.5% (13/17) and number of cases in judgments of excellent, good, fairly improved and no change were 12, 1, 3 and 1 cases respectively. The patients for whom MRSA was isolated from blood were judged as MRSA eradicated case and cured without any additional anti-MRSA drugs. Adverse events were reported in 2 neonates and 3 pediatric patients. Possibly related adverse events to study drug (adverse drug reactions) were: 1 case of respiratory disorder, thrombocythemia, gamma-GTP increased, GOT increased and GPT increased in 3 pediatrics. These results suggest that an application of overseas dose regimen of TEIC for neonate and pediatrics is appropriate in Japan.
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PMID:[Pharmacokinetic and clinical studies on teicoplanin for sepsis by methicillin-cephem resistant Staphylococcus aureus in the pediatric and neonate field]. 1253 39

Lipopolysaccharide is strongly associated with septic shock, leading to multiple organ failure. It can activate monocytes and macrophages to release proinflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and nitric oxide (NO). The present experiments were designed to induce endotoxin shock by an intravenous injection of Klebsiella pneumoniae lipopolysaccharide (LPS, 10 mg/kg) in conscious rats. Arterial pressure and heart rate (HR) were continuously monitored for 48 h after LPS administration. N-Acetylcysteine was used to study its effects on organ damage. Biochemical substances were measured to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-alpha, IL-1 beta, methyl guanidine (MG), and nitrites/nitrates. LPS caused significant increases in blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-alpha, IL-1 beta, MG levels, and HR, as well as a decrease in mean arterial pressure and an elevation of nitrites/nitrates. N-Acetylcysteine suppressed the release of TNF-alpha, IL-1 beta, and MG, but enhanced NO production. These actions ameliorate LPS-induced organ damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound in sepsis prevention and treatment.
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PMID:N-acetylcysteine ameliorates lipopolysaccharide-induced organ damage in conscious rats. 1496 65

Dextromethorphan (DM), an antitussive agent, has been claimed to have anti-inflammatory and immunomodulatory effects in vitro. Thus, the aim of this study was to evaluate the effects of DM on sepsis induced by intravenous (i.v.) administration of lipopolysaccharide (LPS) in anesthetized Wistar rats and by intraperitoneal administration in conscious ICR mice. Results demonstrated that pretreatment with DM (1, 5 and 10 mg/kg, i.v.) significantly attenuated the deleterious hemodynamic changes (e.g., hypotension and tachycardia) in rats treated with LPS. Meanwhile, DM (5 mg/kg) significantly inhibited the elevation of plasma tumor necrosis factor-alpha and interleukin-10 levels, as well as values of GOT and GPT (as an index of liver function), and BUN and creatinine (as an index of renal function) caused by LPS. The induction of inducible NO synthase and the overproduction of NO and superoxide anions by LPS were also reduced by DM. Moreover, infiltration of neutrophils into the lungs and liver of rats 6 h after treatment with LPS was also reduced by DM. In conclusion, the beneficial effects of DM on LPS-induced sepsis result from its anti-inflammatory and antioxidant effects. Thus, DM can possibly be used as a prophylactic agent for sepsis in the future.
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PMID:Dextromethorphan prevents circulatory failure in rats with endotoxemia. 1559 70

N-acetylcysteine (NAC) is an antioxidant and cytoprotective agent with scavenging action against reactive oxygen species and inhibitory effects on pro-inflammatory cytokines. In a previous study, we found that pretreatment with NAC attenuated organ dysfunction and damage, reduced the production of free radicals, tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) following endotoxemia elicited by administration of lipopolysaccharide (LPS). In the present study, we tested the effects of post-treatment with NAC on the sepsis-induced change. Post-treatment imitates clinical therapeutic regimen with administration of drug after endotoxemia. Endotoxin shock was induced by intravenous injection of Klebsiella pneumoniae LPS (10 mg/kg) in conscious rats. Mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 48 h after LPS administration. NAC was given 20 min after LPS. Measurements of biochemical substances were taken to reflect organ functions. Biochemical factors included blood urea nitrogen (BUN), creatinine (Cre), lactate dehydrogenase (LDH), creatine phosphokinase (CPK), aspartate transferase (GOT), alanine transferase (GPT), TNF-alpha, interleukin-6 (IL-6), and interleukin-10 (IL-10). LPS significantly increased blood BUN, Cre, LDH, CPK, GOT, GPT, TNF-alpha, IL-6, IL-10 levels and HR, and decreased MAP. Post-treatment with NAC diminished the decrease in MAP, increased the HR, and decreased the markers of organ injury (BUN, Cre, LDH, CPK, GOT, GPT) and inflammatory biomarkers (TNF-alpha, IL-6, IL-10) after LPS. We conclude that post-treatment with NAC suppresses the release of plasma TNF-alpha, IL-6, and IL-10 in endotoxin shock, and decreases the markers of organ injury. These beneficial effects protect against LPS-induced kidney, heart and liver damage in conscious rats. The beneficial effects may suggest a potential chemopreventive effect of this compound after sepsis.
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PMID:Post-treatment with N-acetylcysteine ameliorates endotoxin shock-induced organ damage in conscious rats. 1686 Mar 47


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