PubMed Health⌕ Search

Biomedical subjects

Helena Isoniemi

Publications and source records attributed to Helena Isoniemi.

18 recordsLinked to original sources
PubMed2007

Chlorpromazine and apigenin reduce adenovirus replication and decrease replication associated toxicity.

BACKGROUND: Adenoviruses can cause severe toxicity in immunocompromised individuals. Although clinical trials have confirmed the potency and safety of selectively oncolytic adenoviruses for treatment of advanced cancers, increasingly effective agents could result in more toxicity and therefore it would be useful if replication could be abrogated if necessary. METHODS: We analyzed the effect of chlorpromazine, an inhibitor of clathrin-dependent endocytosis and apigenin, a cell cycle regulator, on adenovirus replication and toxicity. First, we evaluated the in vitro replication of a tumor targeted Rb-p16 pathway selective oncolytic adenovirus (Ad5/3-Delta24) and a wild-type adenovirus in normal cells, fresh liver samples and in ovarian cancer cell lines. Further, we analyzed the in vitro cell killing efficacy of adenoviruses in the presence and absence of the substances. Moreover, the effect on in vivo efficacy, replication and liver toxicity of the adenoviruses was evaluated. RESULTS: We demonstrate in vitro and in vivo reduction of adenovirus replication and associated toxicity with chlorpromazine and apigenin. Effective doses were well within what would be predicted safe in humans. CONCLUSIONS: Chlorpromazine and apigenin might reduce the replication of adenovirus, which could provide a safety switch in case replication-associated side effects are encountered in patients. In addition, these substances could be useful for the treatment of systemic adenoviral infections in immunosuppressed patients.

Adenocarcinoma↗
PubMed2006

Infectivity-enhanced adenoviruses deliver efficacy in clinical samples and orthotopic models of disseminated gastric cancer.

PURPOSE: Metastatic gastric cancer remains a common and devastating disease without curative treatment. Recent proof-of-concept clinical trials have validated gene therapy with adenoviruses as an effective and safe modality for the treatment of cancer. However, expression of the primary coxsackie-adenovirus receptor is variable in advanced cancers, and therefore, the use of heterologous receptors could be advantageous. EXPERIMENTAL DESIGN: Here, we used capsid-modified adenoviruses for increasing the transduction and subsequent antitumor efficacy. 5/3 chimeric viruses have a serotype 3 knob which allows binding to a receptor distinct from coxsackie-adenovirus receptor. The fiber of Ad5lucRGD is modified with an integrin-targeted motif. Polylysine motifs, pK7 and pK21, bind to heparan sulfates. Oncolytic adenoviruses replicate in and kill tumor cells selectively. Gastric cancer cell lines and fresh clinical samples from patients were infected with transductionally targeted viruses. Capsid-modified oncolytic adenoviruses were used in cell killing experiments. To test viral transduction and therapeutic efficacy in vivo, we developed orthotopic mouse models featuring i.p. disseminated human gastric cancer, which allowed the evaluation of biodistribution and antitumor efficacy in a system similar to humans. RESULTS: Capsid modifications benefited gene transfer efficiency and cell killing in gastric cancer cell lines and clinical samples in vitro and in vivo. Modified oncolytic adenoviruses significantly increased the survival of mice with orthotopic gastric cancer. CONCLUSIONS: These preclinical data set the stage for the clinical evaluation of safety and efficacy in patients with disease refractory to current modalities.

Adenoviridae↗
PubMed2006

Liver transplantation in a patient with sitosterolemia and cirrhosis.

Sitosterolemia (MIM 210250) is a rare genetic disorder caused by disruption of the normal mechanisms that regulate dietary cholesterol absorption and prevent the accumulation of noncholesterol sterols. As a result of this defect, affected individuals accumulate high concentrations of plant sterols in plasma and tissues. They present clinically with tendon or tuberoeruptive xanthomas, premature coronary artery disease, and/or hemolytic anemia. Two genes, ABCG5 and ABCG8, compose the STSL locus, and complete mutation in either, but not both, results in disease. The expression of these genes is confined to the intestine and liver. They are thought to function as sterol efflux pumps. It is not clear which organ, liver or intestine, is of greater importance in maintaining sterol balance with respect to noncholesterol sterols. We report here a case of a patient who presented with "chronic active liver disease" and was found to have sitosterolemia by chance and subsequently underwent orthotopic liver transplantation. Following transplantation, the grossly elevated pretransplantation serum plant sterol levels decreased to values only slightly higher than those of the patient's heterozygous father. This case highlights 2 important features: (1) The liver functions as the predominant organ for maintaining noncholesterol sterol balance (because the intestinal defect was not altered), and (2) a new clinical feature of undiagnosed sitosterolemia may be "idiopathic" liver disease. Because the diagnosis of sitosterolemia is based on specialized plasma analyses, we would propose that some consideration to this diagnosis should be given in appropriate cases.

ATP Binding Cassette Transporter, Subfamily G, Mem↗
PubMed2006

A prospective, randomized, multi-centre trial of systemic adjuvant chemotherapy versus no additional treatment in liver transplantation for hepatocellular carcinoma.

The role of adjuvant systemic chemotherapy in liver transplantation (LT) for hepatocellular carcinoma (HCC) is controversial. Here, we report the results of a Nordic prospective, randomized, multi-centre trial of systemic low-dose doxorubicin in patients with HCC. Between February 1996 and April 2004, 46 patients were randomized to receive either neoadjuvant doxorubicin in combination with LT (chemo group; n = 19) or LT alone (control group; n = 27). In the chemo group, doxorubicin was administered intravenously, 10 mg/m(2) weekly, starting from acceptance onto the waiting list for LT. One intraoperative dose of 15 mg/m(2) was given, and postoperatively doxorubicin was given weekly at a dose of 10 mg/m(2), depending on the clinical course, up to a cumulative dose of 400 mg/m(2). Actuarial, 3-year overall survival (OS) and disease-free survival (DFS) in the control group were 70% and 50%, respectively. In the chemo group, both OS and DFS were 63%. Freedom from recurrence at 3 years was 55% in the control group and 74% in the chemo group. None of the differences was statistically significant. Neoadjuvant treatment with systemic low-dose doxorubicin seems not to improve either survival or freedom from recurrence in patients with HCC undergoing LT.

Aged↗
PubMed2005

Safety and efficacy of a single bolus administration of recombinant factor VIIa in liver transplantation due to chronic liver disease.

Orthotopic liver transplantation (OLT) can be associated with excessive blood loss. As a result, there may be increased risk of adverse outcomes. Activated recombinant factor VII (rFVIIa) has demonstrated the ability to improve hemostasis in a variety of disorders; however, there has been a limited amount of research into its use in OLT. The purpose of this dose-finding study was to examine the efficacy and safety of rFVIIa in the reduction of bleeding in patients undergoing OLT. In this double-blind trial, patients with end-stage liver disease scheduled for OLT were randomized to 1 of 4 parallel study groups. They received a single intravenous bolus of rFVIIa (20, 40, or 80 microg/kg) or placebo prior to surgery. The primary assessment endpoint was the total number of red blood cell (RBC) units transfused perioperatively. Safety was evaluated by adverse events reported. Eighty-three comparable patients were randomized to receive study product, with 82 ultimately undergoing OLT. There were no significant differences in required RBC units between the placebo and rFVIIa study groups. The number of adverse events was comparable between study groups. In conclusion, rFVIIa has a good safety profile in patients undergoing OLT. However, the doses studied did not have any effect on the number of RBC transfusions required.

Adult↗
PubMed2005

Non-invasive diagnosis of liver cirrhosis: magnetic resonance imaging presents special features.

OBJECTIVE: Liver cirrhosis and its complications constitute a daily clinical challenge. The diagnosis of cirrhosis is traditionally established with the invasive method of liver biopsy. We undertook the present study in order to investigate the sensitivity and specificity of magnetic resonance imaging (MRI) in diagnosing cirrhosis. MATERIAL AND METHODS: A total of 56 patients were included in our retrospective study. The liver cirrhosis group comprised 30 patients and the control group 26 patients. All cases were histologically verified. A 1.5T MRI unit was used. Twelve radiological features of cirrhosis (enlargement of segment one, narrowing of hepatic veins, enlargement of spleen, fibrosis, nodular liver surface, ascites, regenerative nodules, enlargement of hilar periportal space, atrophy of right lobe, portosystemic collaterals, expanded gallbladder fossa, iron depositions) and tumour-load were evaluated by consensus reading. The ratio between segment one and right lobe was measured and the livers were classified as cirrhotic or non-cirrhotic. The chi2-test and t-test were used to indicate statistical difference. RESULTS: The sensitivity of MRI in diagnosing liver cirrhosis was 87% and the specificity 92%. The most characteristic MRI features were enlargement of segment one (83%), narrowing of hepatic veins (83%), signs of portal hypertension (77%), fibrosis (77%), and nodular liver margin (67%). There were statistical differences in all MRI signs between the cirrhosis and control groups. The ratio between segment one and right lobe also showed statistical significance between the two groups. All occult hepatocellular carcinomas were detected in the cirrhosis group. CONCLUSION: MRI has high sensitivity and specificity in the diagnosis of liver cirrhosis.

Adult↗
PubMed2005

Sterol parameters as markers of liver function in primary biliary cirrhosis before and after liver transplantation.

Serum cholesterol reflects poorly cholesterol metabolism. From serum noncholesterol sterols cholestanol, campesterol, and sitosterol are surrogate markers of cholesterol absorption, but reflect also cholestasis, while those of lathosterol reflect cholesterol synthesis and hepatic parenchymal function. We investigated these sterols at end-stage of primary biliary cirrhosis (PBC) - prior to liver transplantation and shortly after transplantation in 67 patients to show their role as index of cholestasis and parenchymal liver function. Median preoperative values of cholestanol were increased 7.6 times, those of plant sterols 1.6-3.7 times above and the campesterol/sitosterol ratio was decreased twice below our control values, respective lathosterol levels being mainly subnormal. After transplantation, the proportions to cholesterol of the absorption markers decreased, and those of synthesis markers and the ratios of campesterol/sitosterol increased significantly. Thus, surrogate sterol markers of cholesterol absorption and synthesis in serum are also good clinical markers of chronic cholestasis and degree of hepatic parenchymal cell function in PBC. Postoperative improvement of serum sterol profile indicate clinically good function of the liver graft.

Adult↗
PubMed2004

Value of albumin dialysis therapy in severe liver insufficiency.

A blood purification system, molecular adsorbents re-circulating system (MARS), is based on the removal of both protein-bound and water-soluble substances and toxins in the liver. We treated a total of 88 patients within 2 years. Of these patients, 45 had acute liver failure (ALF), 31 had acute decompensation of chronic liver disease, eight had graft failure and four had miscellaneous conditions. Of the patients with ALF, 80% survived; in 23 patients their own liver recovered and 13 patients underwent successful transplantation. Only 23% of patients with acute-on-chronic liver failure survived. Most of them were not considered for transplantation due to their having liver failure from alcoholism and from not abstaining from drinking. MARS is a promising therapy for ALF, allowing the patient's own liver to recover or allowing enough time to find a liver graft. Best results were achieved in patients who had been intoxicated with a lethal dose of toxin. On the other hand, we did not observe much benefit in patients with severe acute-on-chronic liver failure (AcoChr) who did not undergo liver transplantation.

Acute Disease↗
PubMed2004

Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy.

BACKGROUND/AIMS: Hepatobiliary malignancies are frequently seen in primary sclerosing cholangitis (PSC) and they complicate the evaluation of patients and timing of liver transplantation. METHODS: Data from all Nordic PSC patients listed for liver transplantation during 1990-2001 were recorded prospectively. Predictors of hepatobiliary malignancy and patient survival rates have been analysed. RESULTS: Hepatobiliary malignancy was found in 52/255 (20%) patients accepted to the waiting list. Recent diagnosis of PSC, no ursodeoxycholic acid (UDCA) treatment, clinical suspicion and previous colorectal-cancer were predictors of malignancy. Among 89 patients with a strong suspicion of malignancy prior to acceptance, 35 (39%) had confirmed malignancy. A clinical suspicion had been raised in 35/52 (67%) patients with malignancy. Malignancy was found in 31/223 patients who received a liver allograft. The 1-, 3- and 5-year patient survival rates following transplantation for patients with PSC and cholangiocarcinoma were 65, 35 and 35%, respectively. CONCLUSIONS: Hepatobiliary malignancy is suspected in 1/3 of the PSC patients and found in 1/5. Although cholangiocarcinoma is regarded as a contraindication to liver transplantation (LTX), PSC patients with cholangiocarcinoma had a 35% 5-year survival following transplantation.

Adult↗
PubMed2003

Liver transplantation for primary sclerosing cholangitis in the Nordic countries: outcome after acceptance to the waiting list.

Primary sclerosing cholangitis (PSC) is a common indication for liver transplantation, but evaluation of patients and timing of liver transplantation remain as major problems. Data from PSC and control patients listed for liver transplantation from 1990 through 2000 in the Nordic countries were recorded prospectively. Outcomes from the waiting list and after transplantation have been recorded for both groups. For PSC patients, regression analyses have been performed to analyze predictors of outcome. A total of 255 PSC and 610 control patients were accepted on the liver transplantation waiting list from 1990 to 2000. In the PSC group, 223 patients (87%) received a first liver allograft, and 32 patients (13%) died without transplantation. The corresponding figures for the control group were 89% and 10%. For PSC patients, the 5- and 10-year survival from the time of acceptance was 68% and 58%, respectively. A higher Model for End-Stage Liver Disease score and a shorter duration of PSC predicted death on the waiting list for PSC patients. PSC is a frequent indication for liver transplantation. In our material, serum bilirubin or Model for End-Stage Liver Disease score and PSC duration are predictors of outcome including survival of the waiting list.

Adolescent↗
PubMed2002

Fulminant hepatic failure: outcome after listing for highly urgent liver transplantation-12 years experience in the nordic countries.

Fulminant hepatic failure is a common indication for liver transplantation. Outcomes of patients listed for a highly urgent liver transplantation have been studied, with special emphasis on etiology of the liver disease, clinical condition, and ABO blood type. Data have been collected from the Nordic Liver Transplantation Registry. All Nordic patients listed for a highly urgent primary liver transplantation during a 12-year period have been included. Of the 315 patients listed for a highly urgent liver transplantation, 229 (73%) received a first liver allograft, 50 patients (16%) died without transplantation, and 36 patients (11%) were permanently withdrawn and survived. In 43% of the patients, no definite etiology of the liver failure could be established. Paracetamol intoxication was the most frequent specific indication for listing. Patients with blood type A had no significant shorter waiting time (3.8 v 6.6 days; P =.1) but a higher rate of transplantation (82% v 66%, P =.006) as compared with blood type O patients. In a multivariate analysis, paracetamol intoxication remained the single independent predictor of an outcome without transplantation. In conclusion, a high transplantation rate was observed among patients listed for a highly urgent liver transplantation because of fulminant hepatic failure. Blood type O patients had a lower chance of receiving a liver allograft. Patients with paracetamol intoxication had both a higher mortality without transplantation and a higher withdrawal rate attributable to improved condition.

ABO Blood-Group System↗
PubMed2002

Management and outcome of major bile duct injuries after laparoscopic cholecystectomy: from therapeutic endoscopy to liver transplantation.

Laparoscopic cholecystectomy is associated with a higher rate of bile duct injuries than an open cholecystectomy. The annual incidence of bile duct injuries has remained almost constant and these injuries tend to be more serious, making demands on the method of repair. We wanted to report the management and outcome of major bile duct injuries after laparoscopic cholecystectomy in patients referred to a hepatobiliary and liver transplantation unit. Eighteen patients (14 women), with a median age of 53.5 years were referred to the liver surgery unit with a major bile duct injury after laparoscopic cholecystectomy. The injury was identified after a median of 3 days (range, 0 to 25 days) after operation and the median time interval to referral was 79 days (0 to 2270 days). Fourteen patients had undergone surgery before referral. By the time of referral, four patients had developed end-stage cirrhosis, necessitating liver transplantation. Three of them had undergone bilioenteric drainage operations at the referring institute. Of the remaining 14 patients, three were managed by therapeutic endoscopic procedures. Ten patients were managed with Roux-en-Y hepaticojejunostomy. One died of septic complications before the repair. A median time for hospitalization in our unit was 33 days (range, 10 to 164 days). At present, 16 patients are alive. One patient died of Kaposi's sarcoma 7 months after liver transplantation. A long interval between bile duct injury and referral was associated with the development of end-stage liver disease. Surgery of biliary lesions is demanding, and surgical experience with multidisciplinary approach, including therapeutic endoscopy and liver transplantation, is necessary for successful outcome.

Adult↗
PubMed2002

[MARS].

Explore the source record for details and available documents.

Hepatorenal Syndrome↗
PubMedDate not supplied

Magnetic resonance imaging of the liver: true fast imaging with steady state free precession sequence facilitates rapid and reliable distinction between hepatic hemangiomas and liver malignancies.

OBJECTIVE: To assess the capability of the true fast imaging with steady state free precession (true FISP) sequence in the distinction between hemangiomas and malignant liver lesions. METHODS: Sixty-eight patients with 45 hemangiomas and 51 liver malignancies were included in this study. A 1.5-T magnetic resonance system and a phased-array body coil were used. In addition to true FISP, breath-hold and fat-suppressed, T2-weighted, half-Fourier single-shot turbo spin echo (HASTE) and both unenhanced and gadolinium (Gd)-enhanced T1-weighted sequences were acquired. Two radiologists evaluated the magnetic resonance images independently in a blinded fashion. Interobserver variations with true FISP and HASTE were determined. Lesion contrast-to-noise ratios were calculated from true FISP images. RESULTS: With true FISP, readers 1 and 2 made a correct distinction between hemangiomas and liver malignancies in 43 of 45 (96%) cases and 40 of 45 (89%) cases, respectively. The kappa value was 0.65. With HASTE, the success rates were 40 of 45 cases (89%) and 36 of 45 cases (80%), respectively, and the kappa value was 0.33. With a Gd-enhanced T1-weighted sequence, the correct classifications were 35 of 45 cases (78%) and 37 of 45 cases (82%), respectively. All hemangiomas appeared as bright and well-demarcated lesions on true FISP images. Malignant liver foci were heterogeneous with unsharp margins and nearly isointense relative to liver. The specificities of true FISP in lesion differentiation were 100% and 98% for readers 1 and 2, respectively. The mean contrast to noise ratio value of hemangiomas was 21.2 (standard deviation [SD] = 9.2), and that of malignant lesions was 4.9 (SD = 3.9). This difference was highly significant (P < 0.0001). CONCLUSION: Noninvasive, rapid, and reliable differentiation between hemangiomas and malignant liver lesions is possible by using the true FISP sequence.

Adult↗