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Biomedical subjects

A Dennison

Publications and source records attributed to A Dennison.

At least 19 recordsLinked to original sources
PubMed1996

Beneficial effect of alanine on metabolic recovery of fasted livers submitted to cold ischemia.

The aim of this study was to investigate the possible beneficial effect on perfused mouse liver of alanine as an exogenous substrate for gluconeogenesis. Livers from fed and fasted animals were perfused with oxygenated Krebs' Henseleit buffer for 30 min, then stored at 4 degrees C in University of Wisconsin solution for 48 h. Then reperfusion at 37 degrees C was performed according to two protocols. In the first one, reperfusion with alanine-free Krebs' Henseleit buffer was used for 1 h. 8 mM (3-(13)C) alanine was then added and perfusion was prolonged for a second hour. In the second one, the first hour of perfusion was omitted and the organs were reperfused directly for an hour in the presence of 8 mM (3-(13)C)alanine. 31P NMR was used to measure the NTP recovery of the livers. At the end of the reperfusions, 13C and 1H NMR spectra of perfusates and of glutamine extracted from these perfusates by HPLC were recorded. These data were analysed according to a model of liver metabolism assuming that the only substrate of the liver was (3-(13)C)alanine and endogenous substrates were metabolizable only through pyruvate. It was found that in the absence of initial alanine at reperfusion, livers from fasted mice recovered less NTP than those of fed ones (40 +/- 4% vs 60 +/- 5%, p <0.01), but not if this substrate is present at the beginning of reperfusion (61 +/- 5% vs 60 +/- 5%). This was confirmed by the amount of labelled metabolites produced. However, the dilution of 13C labelled metabolites by unlabelled ones did not indicate a larger concentration of endogenous substrates in livers from fed mice. The conclusion reached was that the lower pyruvate dehydrogenase activity of livers from fasted mice relatively to that from fed mice could be compensated for by the greater pyruvate concentration provided by alanine for the initial production of NTP after cold ischemia and warm reperfusion.

Alanine↗
PubMed1996

Local anaesthesia for major general surgical procedures. A review of 116 cases over 12 years.

Between 1980 and 1992, 116 patients had either a simple mastectomy (32) or intra-abdominal procedures (84) under local anaesthesia (0.5-1% lignocaine with 1:200 000 adrenaline). A wide variety of general surgical procedures were feasible using only supplementary intravenous sedation (54%). Complications were uncommon and related to surgical procedure (three incorrect diagnoses, three procedures impossible) rather than the anaesthetic technique. There were no anaesthetic toxicity or postoperative problems. Local anaesthesia is extremely safe and facilitates larger surgical procedures than is generally appreciated.

Abdomen↗
PubMed1995

The effects of donor and recipient endotoxemia on TNF alpha production and mortality in the rat model of syngenic orthotopic liver transplantation.

The effects of administration of endotoxin to donors or recipients on the mortality rate, evolution of endotoxin levels, and tumor necrosis factor alpha (TNF-alpha) release were investigated in a syngenic orthotopic liver transplantation model in Lewis rats with portal reperfusion only. No significant recipient endotoxemia, TNF-alpha release, or mortality occurred in control recipients following transplantation from normal donors. The doses of endotoxin needed to kill 50% and 100% of animals after hepatic artery ligation were, respectively, 4 mg/kg and 10 mg/kg. Transplantation of animals' livers with no preservation phase from donors who were administered a lethal dose of endotoxin for this combination (10 mg/kg) produced significant recipient endotoxemia at 10 min (6.9 +/- 2.5 x 10(3) endotoxin unit/ml (EU/ml), P < 0.01), 45 min (8.8 +/- 1.1 x 10(3) EU/ml, P < 0.001) and 8 hr (18.5 +/- 3.5 x 10(3) EU/ml, P < 0.001) after graft reperfusion. Significant levels of TNF-alpha were also detected in these animals at 45 min (280 +/- 70 pg/ml, P < 0.007) and 8 hr (80 +/- 40 pg/ml, P < 0.05) when compared with the controls. Mortalities in recipients of OLT from donor animals that had received endotoxin (2 mg/kg or 4 mg/kg) immediately prior to the harvesting procedure was 0% and 20%, respectively, compared with no death in the control group. When recipient animals were administered endotoxin immediately after graft reperfusion the resistance to endotoxin administration was significantly reduced compared with animals that had not received OLT (LD50 < 2 mg/kg versus 4 mg/kg; LD100 4 mg/kg versus 10 mg/kg, respectively). These results show that endotoxin and its effects can be transferred from the liver graft donor to the recipient and that OLT per se reduces the recipient resistance to endotoxin with subsequent increase in mortality.

Animals↗
PubMed1995

Primary anastomosis with transverse colostomy as an alternative to Hartmann's procedure.

Hartmann's procedure remains the favoured option in patients with acute left colonic and sigmoid disease, despite the well documented morbidity and mortality associated with reversal. In 40 patients with left colonic pathology, primary anastomosis was performed; 32 had a covering transverse colostomy. There were six hospital deaths, five in the transverse colostomy group. Closure was not attempted in seven of the 27 patients surviving with a colostomy (three refused, four had disseminated malignancy). In the 20 undergoing closure, there was no morbidity or mortality. With advances in intensive care, antibiotic therapy and anaesthesia, it is reasonable to consider alternatives to Hartmann's procedure, particularly when subsequent reconstruction is envisaged.

Adult↗
PubMed1994

FK 506 renal toxicity and lack of detectable cytochrome P-450 3A in the liver graft of a patient undergoing liver transplantation.

Many commonly used drugs are substrates for hepatic cytochrome P-450 3A in human beings, and its role in the metabolism of potentially toxic immunosuppressants has been highlighted (cyclosporine, FK 506). One hundred fifty human liver grafts were biopsied before and after liver transplantation, and levels of cytochromes P-450 3A, 1A2, 2D6 and 2C were estimated by means of the Western-blot technique and correlated with histological appearance, glycogen content and clinical course. In 15 of the grafts, cyclosporine oxidase was also measured, and in 12 of 15 recipients, urinary 6 beta-hydroxycortisol excretion was assayed. A wide range of cytochrome P-450 3A values were observed (25 to 366 arbitrary units/mg; mean, 105 +/- 63 arbitrary units/mg). In one graft (no. 730) no cytochrome P-450 3A was detectable on immunoblotting, despite increasing homogenate concentrations. In this sample, cytochromes P-450 1A2, 2D6, and 2C were present in normal ranges. Levels of cyclosporine oxidase and 6 beta-hydroxycortisol in the urine specimens of the recipient were found to be low. The recipient of graft 730 experienced reversible complications of FK 506 therapy despite adherence to the administration protocol and drug plasma level in the normal range. The subsequent appearance of the cytochrome P-450 3A was associated with the consequent tolerance of oral FK 506. The absence of detectable amounts of P-450 3A in one biopsy from a donated human liver graft dramatically emphasizes the extreme range of this enzyme levels and has important clinical implications.

Adolescent↗
PubMed1994

A magnetic resonance study of the effect of nutritional status on cold-preserved murine liver.

BACKGROUND/AIMS: Clinical and experimental studies suggest a link between nutritional status and the recovery of hepatic function after hypoxic and hypothermic insults. This study aimed at determining the metabolic pathways involved in such recovery as a function of nutrition. METHODS: Livers from fed and fasted mice were perfused with oxygenated Krebs'-Henseleit buffer (RBKB). After depletion of glycogen, 31P and 13C nuclear magnetic resonance spectra were acquired. Livers were flushed with University of Wisconsin solution and stored at 4 degrees C for 0, 24, or 48 hours. At reperfusion with RBKB, recovery of nucleoside triphosphates (NTP) was followed up. After 45 minutes, [3-13C]alanine was added and substrate consumption and metabolic products assessed. RESULTS: Livers from fed animals recovered more NTP at reperfusion both after 24 hours (85% +/- 11% vs. 67% +/- 7%; P < 0.01) and 48 hours (61% +/- 10% vs. 36% +/- 10%; P < 0.01, respectively) of cold storage. Gluconeogenesis as reflected by [3-13C]alanine consumption was also higher from fed animals. Hepatic glycogen before preservation was low in both groups. Livers from fasted animals contained increased triglyceride levels, but these did not contribute to NTP production at reperfusion. CONCLUSIONS: Livers from fed mice show an improved recovery after cold ischemia. Glycogen levels are low in these organs, and NTP synthesis must be from substrates other than fatty acids.

Adenosine↗
PubMed1994

Transjugular intrahepatic portosystemic shunt worsens the hyperdynamic circulatory state of the cirrhotic patient: preliminary report of a prospective study.

The aim of this prospective nonrandomized study was to assess the immediate and short-term sequelae of transjugular intrahepatic portosystemic shunting on the circulatory hyperdynamic state of the cirrhotic patient. Twelve transjugular portosystemic shunting procedures were performed in 12 cirrhotic patients for sclerotherapy failure (10 cases) and/or intractable ascites (4 cases). Self-expandable stents 10 mm in diameter were used in all cases. Portal pressure measurement and right-heart catheterization were performed before and 30 min and 1 mo after the procedure. The portoatrial pressure gradient decreased from 15 +/- 3 to 7 +/- 3 mm Hg 30 min after surgery (p < 0.0001) to 8 +/- 3 mm Hg 1 mo after surgery (p < 0.001, in comparison with basal values). The cardiac index increased from 4.5 +/- 1.3 to 5.7 +/- 1.5 L/min.m2 30 min after surgery (p < 0.001) to 7.4 +/- 1.4 L/min.m2 1 mo after surgery (p < 0.001). Systemic vascular resistance decreased from 808 +/- 323 to 646 +/- 209 dyne.sec.cm-5 30 min after surgery (p < 0.01) to 467 +/- 101 dyne.sec.cm-5 1 mo after surgery (p < 0.05). This study demonstrates that transjugular portosystemic shunting rapidly and significantly worsens the hyperdynamic circulatory state of the cirrhotic patient. Although apparently noninvasive, this procedure should be considered with caution in cirrhotic patients with limited cardiac reserve.

Adult↗
PubMed1993

Liver resection versus transplantation for hepatocellular carcinoma in cirrhotic patients.

OBJECTIVE: Currently, there is considerable controversy about the place of transplantation in the treatment of hepatocellular carcinoma (HCC). This study compared resection to transplantation in cirrhotic patients with HCC in order to determine reasonable indications of each treatment. SUMMARY BACKGROUND DATA: The usual procedure is to resect when feasible and to transplant in other cases. METHODS: Three-year survival with and without recurrence was analyzed in 60 patients who underwent resection and 60 who underwent transplantation. Several prognostic factors, such as size, number of nodules, portal thrombus, and histologic form, were studied. RESULTS: In terms of overall survival rates, resection and transplantation yield the same results (50% vs. 47%, respectively, at 3 years). For transplantation, however, the rate for survival without recurrence is better than that for resection (46% vs. 27%, respectively; p < 0.05). In the case of small uninodular or binodular tumors (< 3 cm), transplantation has much better results than resection (survival without recurrence, 83% vs. 18%, respectively; p < 0.001). However, it seems that a group of patients with high risk of recurrence after transplantation can be determined (diffuse form, more than two nodules > 3 cm, or presence of portal thrombus). CONCLUSIONS: The best indication for transplantation seems to be patients with small and uninodular or binodular tumors; until now, these patients were considered to be the best candidates for resection. Patients undergoing transplantation for unresectable, large, multinodular or diffuse tumors seem to represent bad indications for transplantation. These results could help define reasonable indications for transplantation in an era with a shortage of liver grafts.

Carcinoma, Hepatocellular↗
PubMed1993

Relationship between graft cytochrome P-450 3A content and early morbidity after liver transplantation.

Cytochrome P-450 3A metabolizes CsA into several metabolites with very limited pharmacological activity and toxicity. In 40 liver donors, the relative concentrations of P-450 3A was assessed by immunoblot analysis using a specific monoclonal antibody exhibited a 10-fold variation (mean = 92 +/- 50 arbitrary units [AU]/mg) in levels. Problems consequent upon CsA usage (nephrotoxicity, neurotoxicity, and hypertension) occurred in 8 of 34 transplant recipients in the immediate postoperative period, and in these 8 patients the problems were always associated with low graft P-4503A levels (mean = 52 +/- 19 A.U./mg, P = 0.0003, cf. patients with no toxicity). Four of these patients had CsA levels that were also high, but 4 had CsA levels in the therapeutic range. Episodes of early graft rejection were related to higher P-450 3A levels (mean = 110 +/- 24 A.U./mg). Cytochrome P-450 3A levels were also found to be inversely related to CsA whole blood levels (assessed with a specific antibody 12 hr after the intravenous infusion of CsA at 1 mg/kg in the recipients (P < 0.02). Cytochrome P-450 3A can provide information that should allow individualized immunosuppression with CsA maintaining therapeutic levels but avoiding toxicity in susceptible individuals.

Adult↗
PubMed1993

Incidence of adverse reactions to cyclosporine after liver transplantation is predicted by the first blood level.

Despite the availability of whole-blood cyclosporine assays, the different responses of individual patients to its administration after transplantation continue to pose clinical problems, particularly with respect to toxicity. Fifty-seven recipients of first orthotopic liver transplants were studied between January 1992 and July 1992. Initial immunosuppression was carried out with azathioprine, methylprednisolone and cyclosporine, at a dose of 1 mg/kg/day adjusted to achieve blood levels between 400 and 600 ng/ml. Cyclosporine levels were measured 12 hr after the start of intravenous administration and correlated with the occurrence of toxic complications. Twelve patients experienced toxic complications in the first 7 days after orthotopic liver transplantation. These were neurological in six patients (of whom four also had kidney failure) and renal complications in the other six patients. All complications were reversed by reducing or stopping administration of cyclosporine. We noted excellent correlation between the occurrence of complications and cyclosporine whole-blood levels (p < 0.0001) despite the fact that levels did not exceed the therapeutic range. However, no correlation was observed between toxicity and cumulative dosage. In this study we were able to demonstrate that a standardized dose of cyclosporine does not prevent the occurrence of toxic side effects even when cyclosporine whole-blood levels are subsequently maintained in the therapeutic range. This highlights the importance of the first dose of cyclosporine and consequent early postoperative blood levels and indicates that these problems are unlikely to be overcome until a method of predicting individual requirements can be established in clinical practice.

Adolescent↗
PubMed1993

Recent developments in liver transplantation.

The many developments that have occurred and continue to occur have also meant that the quality of life experienced by recipients of a successful graft is excellent, with more than 85% of patients returning to normal life and work (even having children). While long-term survival still occurs more frequently in favorable groups such as children with metabolic abnormalities or biliary atresia, results are still extremely good for adults, with 3-year survival figures after transplantation for cirrhosis in the order of 75%. These figures also continue to improve, and with the skill and enthusiasm that workers in this field display they seem destined to continue unabated.

Adenosine↗
PubMed1992

Prospective study in adults of splenic preservation after traumatic rupture.

Seventy-five adults with splenic injury were evaluated prospectively over 45 months to examine the possibility of splenic preservation. Haemodynamically unstable patients underwent surgery with the intent of splenic preservation. Stable patients received non-operative treatment regardless of the grade of splenic injury determined by ultrasonography and computed tomography. Thirty-seven patients required splenectomy and in 38 the organ was preserved (20 operative preservation, 18 non-operative treatment). Of 22 patients initially receiving non-operative treatment, there were four secondary haemorrhages after 7, 7, 10 and 13 days making surgery necessary. Three of these patients underwent splenectomy and in one the spleen was preserved by partial resection. After splenectomy four patients required reoperation because of rebleeding or for evacuation of a haematoma. Patients who had undergone splenectomy had a significantly increased infection rate (P < 0.005) compared with those in whom the spleen was preserved, even when patients were matched with respect to multiple trauma using the Injury Severity Score (P < 0.01).

Adolescent↗
PubMed1990

A randomized comparison of infrared photocoagulation with bipolar diathermy for the outpatient treatment of hemorrhoids.

One hundred two patients with symptomatic hemorrhoids were randomized to receive treatment with either infrared photocoagulation (IRPC) or a bipolar diathermy probe (BD). There was no significant difference in complications, number of treatments required (IRPC 1.7 [0.9], BD 1.6 [0.8]). Third-degree hemorrhoids required more treatments than smaller piles. BD has some practical advantages over IRPC but results are similar.

Ambulatory Surgical Procedures↗
PubMed1986

Morphology of intestinal allograft rejection and the inadequacy of mucosal biopsy in its recognition.

Small intestinal segmental autografts and allografts in dogs were examined histologically to assess changes associated with the surgical technique, the effect of different luminal perfusates and for evidence of rejection. Some animals were immunosuppressed with Cyclosporin A. Specimens for examination were obtained by biopsy at regular intervals after transplantation, at death or when killed. Typical vascular changes of rejection were identified only within some allografts and in others the cause of graft failure remains conjectural. When there was rejection characteristic lesions were confined to the submucosa and muscle coats while changes in the mucosa were similar to those in the autografts. These mucosal features were affected by the nature of the perfusate and often appeared transiently after grafting. Mucosal biopsy as a way of monitoring intestinal allograft rejection neither reveals a sequential pattern of changes, nor provides a reliable method of recognition of the reaction. In contrast full thickness biopsies of the intestinal wall do appear to fulfil both of these requirements.

Animals↗