Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic associated metabolic disorders represent 5% of the indications for orthotopic liver transplantation (OLTX) according to the European Liver Transplant Registry. We studied the outcome of this group at our institution after OLTX and combined liver/kidney transplantation. Between September 1988 and January 1997, 837 OLTXs were performed in 735 patients. Patient survival and graft function at 1 yr were 91.3 and 86%, respectively. Thirty-nine OLTXs were performed in 38 patients (15 female/23 male, median age +/- SD: 35 +/- 14 yr, range 4-60 yr) due to liver associated metabolic disorders (4.7%). Indications included Wilson's disease (n = 14), alpha-1-anti-trypsin-deficiency (n = 7), hemochromatosis (n = 4), erythropoetic protoporphyria (n = 4), cystic fibrosis (n = 2), Crigler-Najjar syndrome type I (n = 1), glycogenosis type I (n = 1), ornithine-transcarbomylase-deficiency (n = 1). In addition 4 patients suffering from primary hyperoxaluria type I received combined liver/kidney grafts. Survival rate the 1 yr after OLTX and combined OLTX/NTX was 91.8%. Twenty patients received cyclosporin A (55%) and 17 patients tacrolimus (45%) as primary immunosuppression. The mean follow-up was 28.6 months (range 4-73 months). Two patients with hemochromatosis died 1 and 3 months after OLTX, respectively, from Aspergillus sepsis followed by multiorgan-failure. One patient died of malignant lymphoma 5 months after transplantation. One patient required retransplantation 2 months after OLTX following arterial thrombosis and ischemic type biliary lesion. One year after OLTX, all patients demonstrated good graft function, liver grafts (ALT 17.9 +/- 13.6 IU/L, bilirubin 0.8 +/- 0.3.mg/dl, thromboplastin time 94 +/- 15%), and combined liver/kidney grafts (creatinine 2.4 +/- 1.4 mg/dl). OLTX, respectively combined OLTX/NTX, represent a successful therapy for hepatic associated metabolic disorders. Survival rates and graft function are similar to those in liver graft recipients for established indications at our institution. OLTX seems to be an excellent treatment for hepatic based therapy resistant neurological disorders.
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PMID:Orthotopic liver transplantation for hepatic associated metabolic disorders. 964 15

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

The vasodilator nitric oxide (NO) is involved in the regulation of systemic blood pressure and local organ blood flow. Inhibitors of the constitutively expressed nitric oxide synthase in endothelial cells (eNOS), e.g., Nomega-nitro-L-arginine methyl ester hydrochloride (L-NAME), aggravated liver injury in a variety of models. On the other hand, inhibitors of the inducible NOS (iNOS), e.g., 2-aminoethyl-isothiourea (AET), were found to be beneficial during endotoxemia. The aim of this investigation was to study the effect of AET compared with L-NAME on liver microvascular blood flow and injury in more complex models with multiple insults, i.e., ischemia (20 min)-reperfusion (8 h) in combination with .5 mg/kg endotoxin (IRE). Male Fisher rats were treated with 10 mg/kg AET or L-NAME and subjected to IRE. At 8 h, liver injury (plasma ALT: 1320+/-164 U/L) was significantly increased in AET-treated (5,018+/-1,379 U/L) and L-NAME-treated groups (2,429+/-228 U/L). Each inhibitor attenuated microvascular blood flow (assessed by laser Doppler flowmetry) to a similar degree. In striking contrast, AET completely reversed the endotoxin-induced impairment of the microvascular blood flow and significantly protected against an endotoxin-induced liver injury (plasma ALT: 3,007+/-268 U/L (ET); 460+/-39 U/L (ET+AET)). Infusion of endothelin-1 reduced microvascular blood flow by 50-60% and caused liver injury. Our data demonstrated that an inhibitor of eNOS (L-NAME) has a consistent detrimental effect on liver injury during ischemia-reperfusion and endotoxemia mainly because it can cause additional ischemia by reducing the microvascular blood flow. However, selective inhibitors of iNOS (AET) can impair hepatic blood flow and aggravate the injury or improve blood flow and attenuate organ injury depending on the experimental model. These results suggest that iNOS inhibitors may not be universally beneficial and should be tested in a variety of experimental models of sepsis/endotoxemia before used in clinical settings.
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PMID:Differential effect of 2-aminoethyl-isothiourea, an inhibitor of the inducible nitric oxide synthase, on microvascular blood flow and organ injury in models of hepatic ischemia-reperfusion and endotoxemia. 968 86

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

Fibrosing cholestatic hepatitis (FCH) has been described as a specific manifestation of hepatitis B virus (HBV) infection in liver allograft recipients characterized by a rapid progression to liver failure. Only sporadic cases have been reported in other immunocompromised groups infected with HBV and in a few transplant recipients with hepatitis C virus (HCV) infection. We present the occurrence of FCH in 4 HCV-infected renal transplant recipients within a series of 73 renal transplant recipients with HCV infection followed up closely serologically and with consecutive liver biopsies. All 4 patients received the triple-immunosuppressive regimen (azathioprine, cyclosporine A, methylprednisolone). The interval from transplantation to the appearance of liver dysfunction was 1 to 4 months and to histological diagnosis, 3 to 11 months. The biochemical profile was analogous to a progressive cholestatic syndrome in 3 patients, whereas the fourth patient had only slightly increased alanine aminotransferase and gamma-glutamyl transferase (gammaGT) levels. Liver histological examination showed the characteristic pattern of FCH in 2 patients, whereas the other 2 patients had changes compatible with an early stage. All patients were anti-HCV negative at the time of transplantation, whereas 2 patients, 1 with incomplete and 1with complete histological FCH features, seroconverted after 3 and 31 months, respectively. The patients were HCV RNA positive at the time of the first liver biopsy and showed high serum HCV RNA levels (14 to 58 x 10(6) Eq/mL, branched DNA). HCV genotype was 1b in 3 patients and 3a in 1 patient. After histological diagnosis, immunosuppression was drastically reduced. Two patients died of sepsis and liver failure 16 and 18 months posttransplantation, whereas the seroconverted patients showed marked improvement of their liver disease, which was histologically verified in 1 patient. In conclusion, FCH can occur in HCV-infected renal transplant recipients. It seems to develop as a complication of a recent HCV infection during the period of maximal immunosuppression and is associated with high HCV viremia levels. There are indications that drastic reduction of immunosuppression may have a beneficial effect on the outcome of the disease.
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PMID:Fibrosing cholestatic hepatitis in renal transplant recipients with hepatitis C virus infection. 1038 2

The onset of liver injury is a pivotal event during endotoxemia. Lipopolysaccharide (LPS) activates the Kupffer cells (KC), the resident macrophages of the liver, to generate an abundance of inflammatory substances, including nitric oxide (NO). Elevated levels of NO are thought to contribute to the propagation of liver injury during sepsis. Calcium, a major second messenger in several cellular signaling events, is required by the KC for the generation of inducible nitric oxide synthase (iNOS). The purpose of this study was to determine whether calcium channel antagonists limit hepatic injury and iNOS expression in vivo following LPS exposure and to evaluate their effects on the regulation of iNOS expression in cultured KC. In rats subjected to LPS for 6 h, the serum alanine aminotransferase (ALT) level was elevated significantly; this response was accompanied by an increase in iNOS mRNA formation in the intact liver. Pretreatment of rats with calcium channel antagonists (i.e., diltiazem, nifedipine, or verapamil) before LPS exposure attenuated the serum ALT level and iNOS mRNA expression in the liver. Pretreatment of cultured KC with calcium channel antagonists for 1 h followed by the addition of LPS markedly repressed iNOS protein and mRNA expression. Time-course studies revealed that calcium channel antagonists were most effective at inhibiting LPS-induced iNOS mRNA formation by KC when added before LPS. Treatment of KC with calcium channel antagonists prior to the addition of LPS decreased nuclear levels of the p65 subunit of nuclear factor-kappaB and prevented the LPS-dependent degradation of the inhibitory protein IkappaBalpha. Thus our findings indicate that under endotoxemic conditions calcium channel antagonists limit hepatocellular injury that is accompanied by an inhibition of LPS-mediated iNOS expression in rat liver KC.
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PMID:Effects of calcium channel antagonists on LPS-induced hepatic iNOS expression. 1044 49

The cardiovascular response to sepsis includes an early, hyperdynamic phase followed by a late, hypodynamic phase. Although administration of pentoxifylline (PTX) produces beneficial effects in sepsis, it remains unknown whether this agent prevents the transition from the hyperdynamic to the hypodynamic response during the progression of sepsis. To study this, male adult rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). At 1 h after CLP, PTX (50 mg/kg body wt) or vehicle was infused intravenously over 30 min. At 20 h after CLP (i.e., the late stage of sepsis), cardiac output and organ blood flow were measured by radioactive microspheres. Systemic and regional (i.e., hepatic, intestinal, and renal) oxygen delivery (DO2) and oxygen consumption (VO2) were determined. Moreover, plasma levels of lactate and alanine aminotransferase (ALT) were measured, and histological examinations were performed. In additional animals, the necrotic cecum was excised at 20 h after CLP, and mortality was monitored for 10 days thereafter. The results indicate that cardiac output, organ blood flow, and systemic and regional DO2 decreased by 36-65% (P < 0.05) at 20 h after CLP. Administration of PTX early after the onset of sepsis, however, prevented reduction in measured hemodynamic parameters and increased systemic and regional DO2 and VO(2) by 50-264% (P < 0.05). The elevated levels of lactate (by 173%, P < 0.05) and ALT (by 718%, P < 0.05), as well as the morphological alterations in the liver, small intestine, and kidneys during sepsis were attenuated by PTX treatment. In addition, PTX treatment decreased the mortality rate from 50 to 0% (P < 0.05) after CLP and cecal excision. Because PTX prevents the occurrence of hypodynamic sepsis, this agent appears to be a useful adjunct for maintaining hemodynamic stability and preventing lethality from sepsis.
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PMID:Pentoxifylline prevents the transition from the hyperdynamic to hypodynamic response during sepsis. 1048 26

Excessive nitric oxide (NO) generated by hepatic cells in response to lipopolysaccharide (LPS) and inflammatory substances (e.g., platelet-activating factor [PAF]) is a key contributor to the pathophysiological outcomes observed in the liver during sepsis. In rats subjected to liver-focused endotoxemia, inducible nitric oxide synthase (iNOS) levels in the intact liver were elevated by 6 hours; cell-specific expression of iNOS messenger RNA (mRNA) was Kupffer cells (KCs), endothelial cells, and hepatocytes. Elevated serum alanine transaminase (ALT) levels at 6 hours confirmed hepatic damage. Pretreatment of endotoxemic rats with PAF receptor antagonists BN 50739 or WEB 2170 reduced serum ALT and iNOS mRNA levels in the intact liver. Pretreatment of cultured KCs with BN 50739 or WEB 2170 inhibited both LPS and PAF-induced iNOS mRNA formation. In addition, LPS-induced iNOS protein levels in KCs pretreated with BN 50739 or WEB 2170 were decreased. Exposure of KCs to either LPS or PAF caused the translocation of the p65 subunit of nuclear factor kappa B (NF-kappaB) into the nucleus and this process was attenuated by BN 50739 and WEB 2170. There was concomitant inhibition of LPS-dependent degradation of the inhibitory protein IkappaBalpha and increase in intracellular Ca(2+) in KC treated with BN 50739 or WEB 2170. Also, in KCs, LPS was able to induce iNOS mRNA expression independent of CD14. This response was inhibited by pretreatment of KCs with either BN 50739 or WEB 2170. Our findings indicate that PAF receptor antagonists convey protection against hepatocellular injury accompanied by a decrease in nitric oxide (NO) formation in the livers of endotoxemic rats.
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PMID:Suppression of lipopolysaccharide-induced nitric oxide synthase expression by platelet-activating factor receptor antagonists in the rat liver and cultured rat Kupffer cells. 1053 42

With improvements in surgical techniques and management of postoperative complications, heart transplantation can now be performed with donors and recipients who were previously considered unsuitable. In this study, we report the results of heart transplantation with marginal donors and recipients in our hospital. From June 1993 through June 1998, we performed 79 heart transplantations. Marginal recipients were defined as those with high pulmonary vascular resistance (> 6 Wood units), severe renal impairment (serum creatinine > 2 mg/dL and creatinine clearance < 50 mL/min), or severe hepatic dysfunction (ALT and AST > 100 IU/L or serum bilirubin > 2.5 mg/dL). Marginal donors were those with any of the following conditions: old age (> 40 years), size mismatch (donor/recipient body weight ratio < 0.8), history of chronic alcohol use, previous cardiopulmonary resuscitation and hypotension, hepatitis B or C virus positivity, coronary artery disease, high-dose dopamine (> 10 micrograms.kg-1.min-1), or prolonged allograft ischemic time (> 4 hours). Of the 79 transplantations performed, 45 (58%) involved marginal recipients or donors. The 30-day mortality rate was 5%, and the 1-year and 5-year survival rates were 87% and 83%, respectively. The survival rates did not differ significantly between cases involving marginal donors or recipients and those involving nonmarginal donors and recipients. There were 27 marginal recipients (34%), only one of whom died during surgery. Five of six recipients with severe renal impairment needed short-term hemodialysis after transplantation. Recipients with high pulmonary vascular resistance had a higher incidence of early acute rejection (5/10 vs 22/69). Thirty-three (42%) of the patients received transplants from marginal donors, four of whom died during surgery; two died of acute vascular rejection, one of allograft failure caused by prolonged ischemic time, and one of bleeding secondary to preoperative sepsis and coagulopathy. These results show that heart transplantation may be performed in marginal recipients and donors, with acceptable operative mortality.
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PMID:Heart transplantation with marginal recipients and donors. 1057 34

The clinical usefulness of injectable biapenem (BIPM) was examined for various infectious diseases in the fields of internal medicine, urology, surgery, orthopedics, obstetrics and gynecology, otorhinolaryngology, ophthalmology, dermatology, oral surgery, and plastic surgery. BIPM was administered by intravenous drip infusion at a dose of 150, 300, or 600 mg twice a day. The concentrations in various body fluid and tissues were also examined. 1. In the total enrollment of 256 cases, the numbers subjected to the analyses for clinical efficacy, bacteriological efficacy, side effects and abnormal laboratory findings were 214, 170, 252 and 251 cases, respectively. 2. The clinical efficacy rate was 85.5% (183/214 cases) as a whole, being 2/2 for sepsis, 6/8 for cellulitis and lymphangitis, 76.2% (16/21) for traumatic, operative wound and burn infections, 4/6 for osteomyelitis and arthritis, 92.9% (13/14) for peritonsillar abscess and peritonsillitis, 83.3% (15/18) for chronic lower respiratory tract infection, 7/7 for pneumonia, 83.3% (30/36) for complicated urinary tract infection, 100% (14/14) for cholecystitis and cholangitis, 88.2% (15/17) for peritonitis, 86.5% (32/37) for internal genital infection, 8/9 for pelvic peritonitis, 2/4 for corneal ulcer, orbital infection and panophthalmitis, 1/2 for otitis media, 4/4 for sinustitis, 93.3% (14/15) for osteitis of jaw and cellulitis of mouth floor. The efficacy rate in the poor responders to the pretreatment by other antibiotics was 86.4% (70/81). 3. 300 strains of causative organisms were isolated from 170 cases which contained polymicrobial infections. The elimination rate of causative organisms was 85.3% (256/300 strains), in terms of bacteriological efficacy. 4. Side effects were noted in 11 of 252 cases (4.4%) with 11 events. The signs and symptoms were the skin symptoms (5 cases), gastro-intestinal symptoms (3 cases), interstitial pneumonia (2 cases), and feeling bad (1 case), all of which disappeared during treatment or after the discontinuation of treatment. The abnormal laboratory findings were observed in 31 of 251 cases (12.4%) with 50 events, and major ones were an increase in eosinophils, and elevations of AST, ALT, gamma-GTP and Al-p. 5. The concentrations of BIPM in body fluid and tissues were determined in 46 cases (212 samples) most of which were administered 300 mg of BIPM by intravenous drip infusion for 60 minutes. The concentrations in the sputum within 6 hours after administration were 0.1-2.5 micrograms/g. The maximum concentrations in body fluid and tissues were 0.2-1.8 micrograms/g or ml in the bile, middle ear mucosa, tonsillar tissue, aqueous humor and bone tissues and were 2.0-5.7 micrograms/g or ml in the gallbladder, maxillary sinus mucous membrane, ethmoidal sinus mucous membrane, oral tissues, skin, woman genitals, synovia, joint tissue, and the eschar. The concentrations in the uterine arterial plasma and retroperitoneal fluid were almost similar to those in the cubitl vein plasma. From the above-mentioned results of clinical efficacy, bacteriological efficacy, and safety, injectable BIPM was confirmed to be useful in the treatment of moderate, severe and/or refractory infections in various fields.
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PMID:[Clinical evaluation of biapenem in various infectious diseases]. 1065 41


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