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Biomedical subjects

N Arkadopoulos

Publications and source records attributed to N Arkadopoulos.

At least 19 recordsLinked to original sources
PubMed2006

The effect of acutely induced hepatic failure on remifentanil and fentanyl blood levels in a pig model.

BACKGROUND AND OBJECTIVE: Opioids and especially fentanyl are widely used during the intensive care unit management of intracranial pressure in fulminant hepatic failure patients as well as during and after liver transplantation. The newer synthetic opioid remifentanil is also increasingly being used in critical care patients. Due to a lack of data relating to the influence of acute hepatic failure on remifentanil and fentanyl pharmacokinetics, this study was designed in order to determine the impact of this condition on the blood levels of these opioids using a pig model. METHODS: Twenty pigs were randomly assigned to one of two groups: A group with surgically induced acute hepatic failure by hepatic devascularization (acute hepatic failure, n=10) and a control group (SHAM, n=10), subjected to a SHAM operation. Postoperatively, five animals in each group were administered remifentanil (1 microg kg-1 min-1) or fentanyl (0.2 microg kg-1 min-1) by continuous intravenous infusion. Blood samples for determination of drug concentrations were withdrawn at 0 h and 0.5, 1, 5, 7, 9 h after initiation of dosing. RESULTS: Significantly higher blood concentrations were found in animals with acute hepatic failure compared to SHAM-operated animals receiving remifentanil at 5 h (P=0.003), 7 h (P=0.007) and 9 h (P=0.004) and fentanyl at 7 h (P<0.0005) and 9 h (P=0.05). The small number and the great variability in drug concentrations did not allow a detailed kinetic analysis to be performed. Approximate clearance values were found to be greater for the SHAM compared with the acute hepatic failure animals for both fentanyl and remifentanil. CONCLUSIONS: Hepatic devascularization in our porcine acute hepatic failure model, appears to have significantly altered the disposition of fentanyl and unexpectedly remifentanil. These changes were thought to be brought about by severe disruption of blood flow and biotransformation in the liver, as well as by haemodynamic changes in the acute hepatic failure animals.

Acute Disease↗
PubMed2006

Urgent thyroidectomy for acute airway obstruction caused by a goiter in a euthyroid pregnant woman.

Pregnancy constitutes a significant factor for thyroid enlargement. However, acute respiratory failure as a result of airway obstruction from an enlarged thyroid gland is an unusual incident. The case presented here concerns a 27-year-old black woman in her 20th gestational week who underwent an urgent operation for removal of a nontoxic, multinodular, mildly substernal goiter that was causing severe upper airway obstruction leading to acute life-threatening respiratory failure. Diagnosis of an extrathoracic tracheal stenosis was based on spirometry with analysis of the flow volume curve and was confirmed by magnetic resonance imaging of the neck. Despite operational risks to the mother as well as the fetus during gestation, an urgent thyroidectomy was carried out successfully. The postoperative period progressed normally and the patient completed her pregnancy with no further respiratory symptoms.

Adult↗
PubMed2002

Haemodynamic changes in ischaemic vs. anhepatic pig experimental model of acute liver failure.

BACKGROUND AND OBJECTIVE: The removal of the non-functioning liver in cases of fulminant liver failure has been advocated by some authors as a means of improving haemodynamic instability and acid-base disturbances associated with acute liver failure. METHODS: The aim of the present experimental study was to investigate whether maintaining a non-functioning liver is preferable over removing it in terms of haemodynamic variables, after acute hepatic failure has been surgically induced. Twenty Landrace pigs were used in the study. All of them underwent portocaval anastomosis and ligation of the hepatic artery. After an 18-h period and with biochemical indices of fulminant hepatic failure clearly demonstrated, the animals were randomly assigned to one of two groups: in 10 pigs (Group A) the ischaemic liver was left in situ and no further surgical intervention was undertaken. The other 10 (Group B) underwent total hepatectomy. Haemodynamic monitoring was the same in both groups. No inotropes were administered throughout the whole period of observation. RESULTS: Haemodynamic deterioration was observed in the hepatectomized pigs (Group B) whereas the group with the ischaemic liver in situ (Group A) remained stable in terms of the haemodynamic variables evaluated until the end of the experiment. (Cardiac index in Group A 7.59 +/- 1.25 L min(-1) m(-2) vs. 2.92 +/- 0.68 L min(-1) m(-2) in Group B, P < 0.05.) CONCLUSIONS: The concept of salvage hepatectomy in cases of acute liver failure should be redefined since there seems to be some experimental evidence that it may not be as beneficial as originally thought.

Analysis of Variance↗
PubMed2001

Bioartificial liver treatment prolongs survival and lowers intracranial pressure in pigs with fulminant hepatic failure.

Intracranial hypertension leading to brainstem coning is a major cause of death in fulminant hepatic failure (FHF). We have developed a bioartificial liver (BAL) utilizing plasma perfusion through a bioreactor loaded with porcine hepatocytes and a column with activated charcoal. In a Phase I clinical trial, we observed a decrease in intracranial pressure (ICP) in FHF patients. However, these patients received BAL therapy together with other measures. We therefore examined whether BAL therapy alone could prevent development of intracranial hypertension in pigs with surgically induced FHF. Pigs (40-60 kg) underwent end-to-side portacaval shunt, transection of all hepatic ligaments, and placement of slings around the hepatic artery and bile duct. After 3 days, the slings were tightened to induce liver necrosis. After 4 h, Group 1 pigs (n = 6) underwent a 6 h treatment with the BAL utilizing 10 billion cryopreserved pig hepatocytes and a charcoal column, Group 2 pigs (n = 6) with the BAL containing charcoal but no cells, and Group 3 pigs (n = 6) with the BAL containing neither cells nor charcoal. Group 1 pigs maintained a normal ICP during BAL treatment and for 14 h afterward and because of this effect they survived longer than Groups 2 and 3 animals. In contrast, Groups 2 and 3 pigs showed an early (6-8 h) rise in ICP.

Analysis of Variance↗
PubMed2001

Activation of hepatic stellate cells in liver tissue of patients with fulminant liver failure after treatment with bioartificial liver.

We studied the explanted livers from 12 patients with fulminant hepatic failure who were treated with a bioartificial liver and subsequently underwent orthotopic liver transplantation and from 18 patients who underwent orthotopic liver transplantation without previous treatment. Ten normal livers were used as controls. In addition to morphologic evaluation, an immunohistochemical analysis was performed with the monoclonal antibodies for alpha-smooth muscle actin and proliferation marker Ki-67. The expression of these markers was graded semiquantitatively from 0 to 3+ in a blinded fashion. The zonal distribution of activated hepatic stellate cells was also evaluated. In all cases, the hepatic stellate cells were activated and expressed alpha-smooth muscle actin. In all patients with submassive or massive liver cell necrosis, the distribution of activated hepatic stellate cells was predominantly in zone 1 of the acinus (periportal area). In contrast, in cases with early nodular regeneration and no significant fibrosis, the activated hepatic stellate cells were distributed throughout the liver parenchyma, involving zones 2 and 3 of the acinus. Expression of the proliferation marker Ki-67 was graded 3+ in all patients treated with the bioartificial liver who had orthotopic liver transplantation and 2+ in patients who underwent orthotopic liver transplantation only.

Actins↗
PubMed2001

Small-bowel herniation under the infrarenal arterial conduit in a liver transplant recipient.

We report a case of herniation of the entire small bowel under an infrarenal conduit 8 months after orthotopic liver transplantation. The conduit was compressed by the mesentery and developed a stricture and thrombosis. Liver revascularization was accomplished by an urgent thrombectomy, resection of the stricture, and reanastomosis of the conduit. Suspicion of this serious complication should arise in transplant recipients who present with bowel obstruction associated with liver dysfunction.

Adolescent↗
PubMed2000

Severe hypothyroidism in patients dependent on prolonged thyroxine infusion through a jejunostomy.

BACKGROUND AND AIMS: Enteral absorption of thyroxine (T4) is variable; the duodenum and jejunum appear to be the most important sites of absorption. Our objective is to demonstrate that T4 infused via a standard jejunostomy may occasionally be poorly absorbed. METHODS: Two patients underwent esophagolaryngeal resection for carcinoma of the cervical esophagus. The procedure was accompanied by complete removal of the thyroid and parathyroid glands. A neck fistula at the gastropharyngeal anastomosis led to a restriction of oral intake; daily requirements of T4 and nutrients were given via the jejunostomy. T4 plasma levels deteriorated and thyroid-stimulating hormone (TSH) levels increased and in the third postoperative week, T4 (300 microg) was administered via a nasogastric tube. RESULTS: Although given a high dose (300 microg) of T4, both patients developed severe hypothyroidism. Infusion of T4 through the nasogastric tube precipitated the normalization of T4 and TSH plasma levels. Both patients (cases 1 and 2) resumed oral intake during the fifth and sixth postoperative weeks respectively. CONCLUSION: T4 malabsorption may occur in patients dependent on prolonged T4 infusion via a standard jejunostomy.

Aged↗
PubMed2000

E. Kondoleon: the man behind the procedure.

UNLABELLED: Historical events and their in-depth analysis have much to teach us about medicine today. Moreover, the lives of those who have made their mark in medical history can be a source of inspiration to future generations of medical scientists. A case in point is the career of E. Kondoleon, originator of the surgical procedure that bears his name. METHODS: Retrieval in the archives of the "Areteion" and "Hippocration" hospitals, where E. Kondoleon had worked and passed away, together with information obtained from the Chair of History of Medicine of the University of Athens, as well as information taken from the Hellenic Surgical Society relative to his life and the motives which led him to the Kondoleon surgical procedure namely: Wide excision of the fascia and concomitant partial excision of the hypertrophic tissue in the treatment of lymphoedema. RESULTS: The Kondoleon operative procedure was not a simple applicable idea of a surgical technique but the result of a long-term systematical study of the anatomy and pathophysiology of the lymphovascular system as well as the continuation of their experimental application. Thus in the beginning of our century, Kondoleon took the lead of carrying out his own technique on the human which for more than 50 years was the object of discussion and application in the treatment of lymphoedema. CONCLUSIONS: Although "the microworld" of the electronic microscope and the conventional microscope of surgery have illuminated many sections of pathophysiology and has led to newer evolutionary tactics (vascular anastomoses, transplantation of lymph-vessels) in the management of lymphoedema, the Kondoleon operative procedure has given the necessary stimuli for these developments. As with other prominent, celebrated men in the history of investigation, Kondoleon had a dramatic end.

Education, Medical↗
PubMed1999

Intracranial pressure during liver transplantation for fulminant hepatic failure.

During orthotopic liver transplantation (OLT) for fulminant hepatic failure (FHF), some patients develop cerebral injury secondary to intracranial hypertension. We monitored intracranial pressure (ICP) and cerebral perfusion pressure (CPP) before and during OLT in 12 FHF patients undergoing transplantation. All four patients who had normal ICP preoperatively maintained normal ICP/CPP throughout OLT. During OLT, four of the eight patients with pretransplant intracranial hypertension had six episodes of ICP increase. These episodes of intracranial hypertension occurred during failing liver dissection (n=3) and graft reperfusion (n=3). At the end of the anhepatic phase, the ICP was lower than the preoperative ICP in all patients, and was below 15 mmHg in all but one patient. These data suggest that in FHF patients who develop intracranial hypertension before OLT, dissection of the native liver and graft reperfusion are associated with a risk of brain injury resulting from intracranial hypertension and cerebral hypoperfusion.

Adult↗
PubMed1999

Bioartificial liver treatment in rats with fulminant hepatic failure: effect on DNA-binding activity of liver-enriched and growth-associated transcription factors.

BACKGROUND: We earlier described a model of fulminant hepatic failure (FHF) in the rat where partial hepatectomy is combined with induction of right liver lobe necrosis. In FHF rats, lack of regeneration of the residual liver was associated with delayed expression of HGF and HGF receptor c-met and elevated blood HGF and TGF-beta1 levels. We then found that intrasplenic hepatocyte transplantation prolonged survival in FHF rats and triggered hepatocyte proliferation in the native liver. The latter effect was associated with accelerated expression of HGF and c-met mRNA in the liver and lowering of blood HGF and TGF-beta1 levels. In the present study we show that in FHF rats, treatment with a bioartificial liver (BAL) had similar effects. MATERIALS AND METHODS: FHF was induced in inbred Lewis rats and after 4 h, Group 1 rats were subjected to a 4-h whole blood perfusion through the BAL loaded with 3 x 10(8) microcarrier-attached syngeneic hepatocytes, whereas Group 2 control rats were treated with the BAL containing microcarriers only. RESULTS: Compared to sham-BAL-treated rats, the test rats lived longer (28 +/- 5 vs 17 +/- 2 h; P = 0.0005), had better coagulation parameters, maintained higher body core temperature, and showed decreased plasma TGF-beta1 levels. In addition, their liver remnants were HGF positive and showed increased DNA binding of transcription factors engaged in the modulation of hepatocyte proliferation (e.g., STAT3) and liver-specific gene expression (e.g., HNF1, HNF4, C/EBP). CONCLUSIONS: This study demonstrates that hepatocyte-based extracorporeal support not only can provide metabolic support by increasing the available functional liver mass but also is capable of modifying humoral and molecular mechanisms which are responsible for proliferation and organ-specific functions of residual hepatocytes.

Animals↗
PubMed1999

Extended esophagolaryngeal resection with parathyroid autotransplantation.

Esopharyngolaryngeal resection for carcinoma of the cervical esophagus must be accompanied by resection of the thyroid gland, parathyroid bodies, and regional lymph nodes. In order to reduce long-term morbidity associated with the procedure, we performed parathyroid autotransplantation in two patients who underwent esophagolaryngeal resections. Grafting of the upper two parathyroid glands into the sternocleidomastoid muscle was carried out successfully in both cases. Graft function was rapidly restored. During the third postoperative week, blood levels of intact parathormone (PTH) reached 20 pg ml(-1) in the first case and 15 pg ml(-1) in the second, and the patients were successfully weaned off calcium and vitamin D supplementation. Parathyroid autotransplantation should be attempted in all cases of esophagolaryngeal resections provided that parathyroid glands are free of malignancy.

Aged↗
PubMed1999

Clinical use of a bioartificial liver in the treatment of acetaminophen-induced fulminant hepatic failure.

Patients with acetaminophen-induced fulminant hepatic failure (FHF) who meet the King's College Hospital criteria have a high mortality risk (>90%) if they do not undergo liver transplantation. We have developed a treatment strategy for these patients based on the use of an extracorporeal bioartificial liver (BAL) support system. In this study, we report the results of the clinical application of BAL support in patients with acetaminophen-induced FHF. All patients were admitted to a dedicated surgical intensive care unit. They were evaluated for urgent liver transplantation and received the standard medical measures, including N-acetylcysteine administration and intracranial pressure monitoring. Moreover, they underwent daily 6-hour BAL treatments. Eight patients were treated. Three patients were bridged to liver transplantation, and five patients recovered without a transplant. All patients experienced neurological and metabolic improvement after treatments with the BAL support system. The BAL support system seems to improve the outcome of high-risk patients with acetaminophen-induced FHF, even in the absence of liver transplantation. Avoiding liver transplantation is particularly important in an era of organ shortage and high cost of transplants.

Acetaminophen↗
PubMed1998

Intrasplenic transplantation of allogeneic hepatocytes prolongs survival in anhepatic rats.

To examine whether hepatocytes transplanted in the spleen can function as an ectopic liver, we performed hepatocyte transplantation in rats that were rendered anhepatic. Total hepatectomy was performed by using a novel single-stage technique. Following hepatectomy, Group 1 rats (n = 16) were monitored until death to determine survival time without prior intervention. Group 2 anhepatic rats (n = 20) were sacrificed at various times to measure blood hepatocyte growth factor (HGF) and transforming growth factor beta1 (TGF-beta1) levels. Group 3 (n = 16) rats received intrasplenic injection of isolated hepatocytes (2.5 x 10(7) cells/rat) followed by total hepatectomy after 3 days. Group 4 (n = 12) sham-transplanted rats received intrasplenic saline infusion, and after 3 days they were rendered anhepatic. Group 2, 3, and 4 rats were maintained on daily Cyclosporine A (10 mg/kg; intramuscularly). Group 1 anhepatic rats survived for 22.4 +/- 5.2 hours (standard deviation). The anhepatic state was associated with a progressive and statistically significant rise in blood HGF and TGF-beta1 levels. Rats that received hepatocyte transplantation before total hepatectomy had a significantly longer survival time than sham-transplanted anhepatic controls (34.1 +/- 8.5 vs. 15.5 +/- 4.8 hrs, P < .01). Additionally, at 12 hours post-hepatectomy, transplanted rats had significantly lower blood ammonia, prothrombin time, international normalized ratio, and TGF-beta1 levels when compared with sham-transplanted controls. In conclusion, intrasplenic transplantation of allogeneic hepatocytes prolonged survival, improved blood chemistry, and lowered blood TGF-beta1 levels in rats rendered anhepatic.

Ammonia↗