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Algorithm for assessing renal dysfunction risk in critically ill trauma patients receiving aminoglycosides.

A recent retrospective study proposed that the following screening criteria be used in identifying critically ill trauma patients receiving aminoglycosides who are at significant risk to develop renal dysfunction: (1) post-admission shock, (2) minimum serum concentration more than 2 mg/L, and (3) diagnosis of septicemia. The major purpose of the present study was to validate these criteria and design a corresponding algorithm for clinical use. All patients admitted to a trauma intensive care unit and receiving an aminoglycosides was also studied. All patients studied over a 7-month period. A control group not receiving aminoglycosides was also studied. All patients were evaluated for the presence of renal dysfunction (i.e., serum creatinine increase greater than or equal to 0.5 mg/dL). Univariate and multivariate statistical analyses were used to compare potential associated risk factors. The overall renal dysfunction incidence was 10% in the treatment patients (n = 93) versus 5% in the control patients (n = 199) (p = 0.13). Sensitivity and specificity of the screening criteria were 67% and 92%, respectively. The predictive values of a positive and negative test relative to correctly labeling patients at high risk or low risk to develop renal dysfunction were 46% and 96%, respectively. Major risk factors associated with renal dysfunction in the treatment group were post-admission shock, minimum serum concentration more than 2 mg/L, and liver dysfunction. Use of three major risk factors has excellent predictive value in identifying severely traumatized patients at low risk for developing renal dysfunction while receiving aminoglycosides. The modest predictive value of a positive test results in conservative management of patients by avoidance of aminoglycosides, i.e., use of alternative antimicrobial agents.

Acute Kidney Injury↗

Outcome of cystic fibrosis-associated liver cirrhosis: management of portal hypertension.

BACKGROUND/AIM: Variceal bleeding is the most severe complication in patients with cystic fibrosis-associated liver cirrhosis, who often do not have severe respiratory failure. The advent of liver transplantation has broadened the treatment options. The purpose of this study was to report our experience with the management of portal hypertension. METHODS: Clinical and biochemical features, outcome of liver disease and management of portal hypertension were analyzed retrospectively in 44 children with cystic fibrosis-associated liver cirrhosis. RESULTS: The mean age at diagnosis of liver cirrhosis was 9 years. Eighty-six per cent of the children developed esophageal varices, 50% of whom bled early in their second decade. Injection sclerotherapy of esophageal varices did not prevent recurrence of bleeding in five of seven children. Elective surgical portosystemic shunting was successfully performed in nine of 11 patients considered being at high risk of bleeding or with recurrent bleeding episodes but without severe pulmonary failure and liver dysfunction, allowing prolonged post-operative survival up to 15 years. Two of three children who underwent isolated liver transplantation for severe portal hypertension died post-operatively. CONCLUSIONS: Management emphasis in cystic fibrosis patients with liver cirrhosis should be on control of bleeding and variceal decompression. These results suggest that surgical portosystemic shunting may be considered to relieve portal hypertension in patients without progressive liver failure and severe lung disease as an alternative to liver transplantation. With this policy, patients may be stabilized for many years until progression of liver or lung diseases indicates liver or lung-liver transplantation.

Adolescent↗

Successful allogeneic bone marrow transplantation in a 2.5-year-old boy with ongoing cytomegalovirus viremia and severe aplastic anemia after orthotopic liver transplantation for non-A, non-B, non-C hepatitis.

BACKGROUND: A 2.5-year-old boy received a cadaveric orthotopic liver transplant for acute liver failure due to non-A, non-B, non-C hepatitis. After transplantation, he developed thrombocytopenia and neutropenia and subsequently severe aplastic anemia. The patient also suffered from recurrent cytomegalovirus (CMV) viremia, treated with foscarnet and ganciclovir. METHODS: For treatment of his aplastic anemia, the patient underwent an allogeneic bone marrow transplantation from his HLA-identical sister after conditioning with cyclophosphamide at 200 mg/kg and antithymocyte globulin at 3 mg/kg for 5 days. Prophylactic acyclovir was given because of ongoing CMV viremia at the time of bone marrow transplantation. RESULTS: The transplant course was uneventful, with rapid engraftment. There were no signs of liver dysfunction, graft-versus-host disease, or reactivation of CMV. The patient is in excellent health, with normal liver and bone marrow function 3 years after bone marrow transplantation. CONCLUSION: This case report shows that allogeneic bone marrow transplantation is feasible and well tolerated in a patient with severe aplastic anemia after liver transplantation for acute fulminant viral hepatitis.

Anemia, Aplastic↗

Erythropoietic protoporphyria. Hepatic implications.

The terminal stages of erythropoietic protoporphyria are recorded. The observations are related to the site of the fundamental lesion and the nature of the biochemical defect. The possibly ominous prognosis in this usually mild condition is emphasized. Apart from congenital porphyria, the porphyrias do not usually confer severe cutaneous lesions. These diseases present to dermatologists because of moderate photosensitivity and are not usually regarded as a risk to life. Dangerous central nervous system involvement may occur, however, in acute intermittent, variegate and hereditary coproporphyrias, while in acquired symptomatic porphyria severe underlying liver dysfunction may occur. Probably the most common familial photosensitizing porphyria is erythropoietic protoporphyria. Recently some deaths from severe liver involvement have been reported in this disease.

Feces↗

Fatal hepatic necrosis after shock.

A clinicopathological study was undertaken in 15 cases of massive hepatic necrosis after shock. The GOT and GPT level exceeded 1000 units in 10 cases. The 15 cases consisted of 3 diagnosed as fulminant hepatitis clinically and 12 diagnosed as disseminated intravascular coagulation (DIC) or multiple systemic organ failure (MOF) from the unremarkableness of liver dysfunction. It was noteworthy that sepsis and surgery were closely associated with these lesions. The weight of the liver at autopsy ranged from 800 to 2,700 g. Liver necrosis was macroscopically characterized by clear demarcation of the necrotic areas sharply separated from the surrounding liver parenchyma, showing the appearance of so-called "map-like necrosis". Microscopically, the lesions in these subjects showed mainly the pattern of centrilobular necrosis. As observed in the burn shock case (case 12), the shock which provoked in different phases of time seemed to have repeated its attack. These liver necroses were considered to result from severe systemic circulatory disturbance or intrahepatic circulatory disturbance. The possibility is indicated that the generalized or univisceral Shwartzman reaction, and repeated and combined severe shock participated in the pathogenesis. Fibrin thrombi aggrevate tissue perfusion and accelerate anoxia. Heparin therapy seemed effective in these cases if administered at an appropriate time.

Adolescent↗

Epstein-Barr virus (EBV)-induced CD30+ natural killer cell-type malignancy resembling malignant histiocytosis: malignant transformation in chronic active EBV infection associating hypogammaglobulinemia.

A 27-year-old male suffered from Epstein-Barr virus (EBV)-related liver dysfunction with persistent hypogammaglobulinemia. IgG titers to EBV antigens were significantly high, while other hepatitis markers were negative. Liver biopsy disclosed active intralobular inflammation. Two years later, he manifested persistent fever, leukopenia, effusions and hypoproteinemia, and his general condition worsened progressively. The peripheral blood small lymphocytes predominantly expressed natural killer (NK)-like phenotypes (CD2+, CD7+, CD16+, CD56+). Hepatosplenomegaly and marked elevation of serum lactic dehydrogenase were observed. He died of respiratory failure at the age of 29. At autopsy, the liver (2190 g), spleen (860 g), small bowel and mesenteric lymph nodes showed massive infiltration of large atypical lymphoid cells in close association with hemophagocytic histiocytes. Involvement was mildly noted also in the bone marrow, lungs, gall-bladder and kidneys. The atypical cells belonged to CD30+ activated NK-type cells expressing CD2, cytoplasmic CD3 epsilon, CD7, CD45RO, CD56, HLA-DR and HLA-DQ. T cell receptors (TCR), surface CD3, CD4, CD5 and CD8 were not expressed. Epstein-Barr virus-related small nuclear RNA (EBER1) and Epstein-Barr virus-associated nuclear antigen 1 were detected in the nuclei of a significant number of atypical cells, while EBV-related latent membrane protein-1 was negative. EBER1 was also identified in the nuclei of non-neoplastic small lymphocytes at both biopsy and autopsy. Monoclonal integration of the EBV genome into the lymphoma cells was shown by Southern blot analysis. Clonal rearrangement of TCR was undetectable. Roles of chronic active EBV infection in the development of NK cell-type malignancy resembling malignant histiocytosis are discussed.

Adult↗

Complete caudate lobectomy: its definition, indications, and surgical approaches.

There are three ways to approach and resect the caudate lobe of the liver, that is; and isolated caudate lobectomy, a combined resection of the liver overlying the caudate lobe, and a transhepatic anterior approach by splitting parenchyma of the liver. We had two patients with neoplasms originating in the caudate lobe who underwent a complete caudate lobectomy. Both patients have been doing well without liver dysfunction. Although after the transhepatic anterior approach we anticipated an adverse effect from splitting the parenchyma of the liver, the postoperative course was uneventful and similar to that of the right side approach.

Adenocarcinoma↗

Safety issues with statin therapy.

OBJECTIVE: To describe the most important potential adverse effects related to statin therapy, discuss mechanisms of toxicity and drug interactions, and suggest approaches for enhancing safety with statin therapy. DATA SOURCES: Large-scale clinical trials, government databases and papers, and recent studies of statin safety. STUDY SELECTION: By the author. DATA EXTRACTION: By the author. DATA SYNTHESIS: The number of patients requiring intensive therapy with statins to achieve lipid goals is climbing, and as the number grows, so does the potential for adverse effects with these agents. The most detrimental adverse effects of statins are hepatotoxicity and myopathy. Liver dysfunction induced by statins is rare and usually mild, with asymptomatic transaminase elevation or acute cholecystitis. Progression to liver failure is exceedingly rare, and transaminase elevations is usually reversible with dose reduction. Statin-associated myopathy is generally a concern when patients have more than one risk factor for muscle syndromes, such as an elderly patient with poor renal function. Drug interactions represent an additional concern, especially for atorvastatin, lovastatin, and simvastatin, all of which are metabolized by the important 3A4 isoenzyme of the cytochrome P450 system of the liver. CONCLUSION: The benefits of all available statins for the treatment or prevention of cardiovascular disease outweigh any potential risks of therapy. For patient groups most susceptible to adverse effects, such as the elderly and those on multiple medications, clinicians should consider the use of statins that are least likely to interact with other medications.

Chemical and Drug Induced Liver Injury↗

Graves' disease accompanied by anti-myeloperoxidase antibody-related nephropathy and autoimmune hepatitis.

A 17-year-old woman was admitted because of proteinuria, microhematuria and liver dysfunction with increased antinuclear antibody and anti-myeloperoxidase antibody (MPO-ANCA). Fourteen months' previously, urinalysis and liver function showed normal range. At that time she suffered from tachycardia and weight reduction, diagnosed as Graves' disease, she was given propylthiouracil for treatment of her Graves' disease. The histological finding of renal biopsy was compatible with minor glomerular abnormalities. Liver biopsy finding was compatible with autoimmune hepatitis. After we had administered prednisolone, liver function returned to normal range and urine protein became negative. Then we performed subtotal thyroidectomy, and she was not given propylthiouracil. MPO-ANCA decreased gradually.

Adolescent↗

An autopsy report of graft-versus-host disease (GVHD) following blood transfusion.

A case of graft-versus-host disease (GVHD) associated with blood transfusion in a 71-year-old man is reported. The patient received transfusions (irradiation red cells M.A.P 14 units, fresh frozen plasma 11 units) and developed features of GVHD including fever, a skin rash, diarrhea, liver dysfunction, hypoplastic bone marrow, and pancytopenia. He died on day 32 posttransfusion. Pathologically, lymphocyte infiltration of skin and liver lesions, degeneration of small bile ducts, crypt cell necrosis in the gastrointestinal tract, and bone marrow hypoplasia were observed. Immunohistochemically, infiltrating lymphocytes were CD8+ T type, the result suggesting that they role a part in posttransfusion GVHD.

Aged↗

[Efficacy of continuous hepatic arterial infusion of high-dose 5-FU for liver metastases of gastric cancer].

We studied the efficacy of continuous hepatic arterial infusion of high-dose 5-FU (high-dose CHAI) in two patients with multiple (five or more) bilobar liver metastases of gastric cancer. 5-FU was given continuously via the hepatic artery at 1 g/day for 3 days, followed by one day off therapy and repetition of the initial treatment as one course. Case 1 was a 67-year-old man with Borrmann type 2 gastric cancer who had undergone total gastrectomy. Metachronous multiple liver metastases (maximum diameter: 3.5 cm) were detected at 11 months after surgery. One month later, we started high-dose CHAI and gave two courses with a 4-day interval between them. After that, 5-FU was given twice by hepatic arterial infusion (HAI) at dose of 1.5 g/week. The tumor diameter had decreased by 50% at 3 months after high-dose CHAI. Case 2 was a 64-year-old man with Borrmann type 3 gastric cancer who had synchronous multiple liver metastases (maximum diameter: 9 cm) and liver dysfunction. One month after distal gastrectomy, we started high-dose CHAI and finished one course. After that, liver function returned to normal and 5-FU was given by HAI at dose of 1 g/week on an outpatient basis. The tumor diameter decreased to 1/3 of the initial size at four months after high-dose CHAI. High-dose CHAI using 5-FU may be safe and effective for liver metastases from gastric cancer.

Aged↗

[A case of polymyositis associated with primary biliary cirrhosis].

We studied a 67-year-old female suffered from polymyositis associated with primary biliary cirrhosis. She was pointed out liver dysfunction by screening test. Alkaline phosphatase, transaminase, and IgM were increased. Antimitochondrial antibody and antinuclear antibody were positive. Liver biopsy showed cell infiltrations in Glisson's capsules and destruction of cholangioles, being diagnosed as primary biliary cirrhosis (Scheuer Stage I). Four years later she showed a muscle weakness of four extremities and admitted to our department. Neurological examination revealed a severe weakness and atrophy of both proximal and distal muscles. Deep tendon reflex was decreased on four extremities. Laboratory examination showed a creatine kinase level of 312 IU/L, alkaline phosphatase 238 IU/L, gamma-glutamyl-transpeptidase 140 IU/L, Igm 416 mg/dl, antimitochondrial antibody titer 1:320, and antinuclear antibody titer 1:320. Muscle biopsy findings were compatible with polymyositis. Electron microscopic examination disclosed diffuse increase of mitochondria in subsarcolemma and intermyofibrils. Until now eight cases with polymyositis associated with primary biliary cirrhosis have been reported, but electron microscopic examination of muscle has not been carried out. It is necessary to examine mitochondria of muscle and liver in patients with polymyositis associated with primary biliary cirrhosis for the elucidation of its etiology.

Aged↗

Liver transplantation.

The development of liver transplantation has been difficult. However, substantial advances have been made mostly because of better surgical techniques and because of better postoperative management. It has been necessary for surgeons to be more inquisitive about the reasons for post-transplantation liver dysfunction rather than to ascribe hepatic perturbations to rejection. With these nonspecific improvements, there has been movement of liver transplantation into the area of actual service. Before the next great step will be made, there must be an improvement in immunosuppression. The nature of such improvement is not yet clear.

Adult↗

Serum bile acids (a new advance in the diagnosis of liver disease).

Serum bile acid measurements now available by radioimmunoassay have proven to be the most sensitive procedure developed to date to assess diseases of the hepatobiliary system in both adult and pediatric liver disease. Their clinical utility appears to hold particular promise in establishing the early diagnosis of liver disease when conventional liver function test such as SGOT, alkaline phosphatase, bilirubin and albumin are still normal. Serum bile acid determinations have been shown to be particularly useful in the diagnosis of alcoholic liver disease, drug-induced liver disease, viral hepatitis and cholestasis of intra- and extrahepatic origin. In infants, serum bile acid measurements can be used to establish the diagnosis of biliary atresia. When serum bile acids are determined post-prandially, they are the most sensitive indicator of liver dysfunction developed to date.

Bile Acids and Salts↗

[Use of the RBJ-131 test for evaluation of liver lesions in persons chronically exposed to carbon disulfide].

34 patients chronically exposed to carbon disulphide have been examined. In order to evaluate lesion of the liver in all the patients there have been determined: CBJ131 atrophy half-period in blood, the concentration of total cholesterol and its esters, the concentration of total lipoproteids and beta-lipoproteids. In addition, proteins in blood serum have been electrophoretically separated. Among all the parameters analysed, the greatest percentage of liver dysfunction has been found by the CBJ131 test. This test seems to be very useful for evaluating the liver lesion in those with suspected chronic carbon disulphide poisoning.

Adult↗

Clinical value of the determination of fasting glycocholic acid serum levels in patients with liver diseases. A comparison with standard liver tests.

Fasting serum levels of glycocholic acid were measured in 142 patients with benign diffuse liver diseases. A total of 63.4% of the whole group of patients, 86.6% of the cirrhotic patients and 31.7% of the noncirrhotic patients had increased serum levels of glycocholic acid. There were significant correlations with blood liver tests associated with liver disease severity such as prothrombin activity and albumin. There were highly significant differences in glycocholic acid levels according to the histological severity of the liver disease, especially when patients with cirrhosis or chronic active hepatitis were compared to the remaining patients and controls. However, discriminant analysis showed that prothrombin activity and albumin were better than glycocholic acid in predicting the histological severity of liver disease. Glycocholic acid serum levels were relatively independent of cholestasis and cytolysis and appeared to be more linked to liver dysfunction. In conclusion, fasting glycocholic acid measurement can be useful in the evaluation and follow-up of liver diseases as a marker of histological severity, and used in addition to other liver tests.

Adolescent↗

Tubulointerstitial nephropathy persisting 20 months after discontinuation of chronic intake of germanium lactate citrate.

Two young human immunodeficiency virus (HIV)-infected patients, a 25-year-old woman and a 26-year-old man, consumed large amounts of germanium lactate citrate 18% as an "immunostimulant" for 9 months. The woman, who had stage II HIV infection, developed severe renal dysfunction (creatinine clearance, 7 mL/min/1.73 m2) and slight proteinuria (0.28 g/d) after ingesting 260 g germanium lactate citrate 18%. Hepatomegaly with liver dysfunction (SGOT, 102 U/L; gamma-glutamyl transferase (GT), 159 U/L) and lactic acidosis (plasma lactate, 7.3 mmol/L) developed simultaneously. Renal biopsy revealed tubulointerstitial nephropathy with vacuolar cell degeneration and periodic acid-Schiff-positive intracellular deposits mainly in distal tubules. Liver biopsy disclosed severe hepatic steatosis; liver function tests returned to normal within 5 weeks. Since renal failure persisted for 2 years after ingestion of germanium (creatinine clearance, 14 mL/min/1.73 m2; proteinuria, 0.84 g/d), a second renal biopsy was performed, which showed marked but focal distal tubular atrophy and slight interstitial fibrosis. The male patient, who had stage III HIV infection, had ingested the same compound; he presented with a creatinine clearance of 43 mL/min/m2 and proteinuria of 0.36 g/d. Renal biopsy disclosed tubulointerstitial changes similar to those found in the female patient. After 9 months off germanium, creatinine clearance remained unchanged. Neutron activation analysis of all biopsy specimens in both cases documented germanium concentrations 10 to 70 times normal in renal tissue and 140 times normal in liver tissue.

Adult↗

[A case of advanced cholangiocellular carcinoma treated successfully by percutaneous isolated liver perfusion with cisplatin].

Herein reported is a case with unresectable intrahepatic cholangiocellular carcinoma (CCC) treated successfully with high-dose cisplatin infusion under hepatic venous isolation and charcoal hemoperfusion (HVI.CHP). The patient was a 43-year-old woman, who was investigated for liver dysfunction and subsequently referred to our institution with a diagnosis of unresectable intrahepatic CCC. We gave this patient a total of 2 treatments of percutaneous isolated liver perfusion with HVI.CHP (a total dose of cisplatin, 400 mg and adriamycin 30 mg). Although she had a slight elevation of serum GOT levels, leukopenia and renal dysfunction did not occur throughout the posttreatment course. The level of DUPAN-2 after the first treatment showed a marked reduction to 910 U/ml, from a pretreatment level of 2,700 U/ml. Abdominal CT scan also demonstrated a remarkable regression of liver tumors (PR: volume reduction, 76%). In conclusion, in percutaneous isolated liver perfusion using HVI.CHP, we have safely accomplished a dose intensification of intraarterial cisplatin. The treatment resulted in a marked tumor regression. Therefore, we consider that this method offers an effective therapeutic option for unresectable CCC.

Adult↗