Ralitrexed (Tomudex) or Nordic-FLv regimen in metastatic colorectal cancer: a randomized phase II study focusing on quality of life, patients' preferences and health economics.

Raltitrexed (Tomudex) is proven effective in metastatic colorectal cancer. Between 1998-2000, 25 patients were included in a randomized phase II study comparing raltitrexed (13 patients) and the Nordic FLv regimen (12 patients). 23 patients were evaluable for response. The overall response rate was 2/12 (1 CR, 1 PR) in the raltitrexed arm and 1/11 (1 CR) in the Nordic FLv arm, respectively. There was no difference in overall survival (raltitrexed--14.7 months, Nordic FLv--15.4 months). 23 patients were evaluable for Quality of Life (QoL) analysis. 23/25 and 17/21 questionnaires (EORTC QLQ C-30) were returned at baseline and first evaluation. Raltitrexed tended to be the most toxic regimen, when looking at nausea and vomiting, appetite loss, diarrhea and global QoL. However, most patients (65%) recommended the raltitrexed treatment schedule. The total treatment cost was equal in both arms (about 6,800 EURO/patient) and the hospital/hospital hotel stay costs accounted for more than half of it.

[Laparoscopic hernia repair. A useful method for surgical treatment of inguinal hernia?]. / Laparoskopisk brokkreparasjon. Brukbar metode i kirurgisk behandling av lyskebrokk?

Between September 1992 and May 1993 14 groin hernias in 13 patients were treated with laparoscopic transabdominal preperitoneal repair using a polypropylene mesh to reinforce the abdominal wall. There were two indirect and 12 direct hernias. Five hernias were recurrent. There were no perioperative complications. In the follow up period 14-24 months after the operations, two patients developed recurrent hernias after four and ten months respectively, one patient presented with a new hernia on the contralateral side, and one patient died from cardiac disease. Laparoscopic hernia repair is technically demanding and in our setting is more time- and resource consuming than an open, tension-free repair. Thus it is questionable whether this method should be used in primary hernia repair. It may, however, have a place in the treatment of recurrent hernias and bilateral hernias.

Intraosseous infusion of a small volume of hyperosmotic fluid increases mean arterial pressure and lessens the catecholamine response in pigs with haemorrhagic shock.

OBJECTIVE: To measure the plasma catecholamine concentrations during an episode of haemorrhagic shock treated by intraosseous infusion of a small volume of hyperosmotic fluid in a standardised porcine model. DESIGN: Randomised open study. SETTING: University hospital, Norway. MATERIAL: 14 piglets. INTERVENTION: Two groups of piglets (n=7 each) were anaesthetised with ketamine and bled to a mean arterial pressure of 40 mm Hg. After 30 minutes the animals were randomised to receive 100 ml of either hyperosmotic (2.4 mo/l) or iso-osmotic (0.29 mo/l) fluid (equal volumes of glucose and sodium chloride) into the tibial bone marrow. MAIN OUTCOME MEASURES: Short term (70 minutes) observation of changes in haemodynamic, biochemical and hormonal variables. RESULTS: The hyperosmotic infusion significantly improved the circulation (mean arterial pressure and cardiac index) compared with the iso-osmotic infusion (p < 0.05). The increased plasma catecholamine concentrations returned to the reference ranges 20 minutes after the hyperosmotic infusion, and were significantly different (p < 0.05) from the catecholamine concentrations observed in the iso-osmotic treatment group. CONCLUSION: Intraosseous hyperosmotic resuscitation increases the circulatory performance and reduces the plasma catecholamine concentrations during haemorrhagic shock in pigs.

Influence of intra-osseous infusion of a small volume of hyperosmotic fluid on beta-adrenergic function in circulating lymphocytes from bled pigs.

The regulation of beta-adrenergic function in circulating mononuclear leukocytes was evaluated during an episode of haemorrhagic shock treated by intra-osseous infusion of a small volume of hyperosmotic fluid. Two groups of piglets (n = 14) were anaesthetized with ketamine and bled to a mean arterial pressure of 40 mmHg. After 45 min the animals were randomized to receive 100 ml of either hyperosmotic (2.4 mol l-1) or iso-osmotic (0.29 mol l-1) fluid (equal volumes of glucose/sodium chloride) into the tibial bone marrow. Observations of haemodynamic variables and levels of plasma catecholamines and cAMP of circulating mononuclear leukocytes were carried out for 70 min. Infusion of hyperosmotic fluid enhanced the circulatory performance and attenuated the plasma catecholamine release significantly (p < 0.05) compared to the corresponding values in the animals that had iso-osmotic fluid infusion. Measurements of unstimulated and isoprenaline-stimulated cAMP levels in mononuclear lymphocytes indicated that the high plasma catecholamine levels in the iso-osmotic treatment group induced a desensitization of the beta-adrenoceptors 70 min after initiation of the shock. This effect was not seen in animals that had undergone hyperosmotic infusion.

Effect of haemorrhagic shock and intraosseous resuscitation on plasma and urine catecholamine concentrations and urinary clearance in pigs.

OBJECTIVE: To evaluate the plasma and urinary catecholamine concentrations after episodes of haemorrhagic shock treated by intraosseous infusion of a small volume of hyperosmotic fluid, followed by whole blood, in a standard porcine model. DESIGN: Randomised open study. SETTING: University hospital, Norway. MATERIAL: 18 piglets. INTERVENTIONS: All animals were bled to an arterial systolic pressure of 60 mm Hg. After 30 minutes 100 ml hyperosmotic (2.4 mol/l) fluid (glucose/sodium chloride) was given either intraosseously (n = 6) or intravenously (n = 6). Ninety minutes later the animals were again bled to a systolic pressure of 60 mm Hg, and after 30 minutes an autologous whole blood transfusion was given by either intraosseous or intravenous infusion. Six animals acted as untreated controls. MAIN OUTCOME MEASURES: Changes in haemodynamic variables and plasma and urinary catecholamine concentrations. RESULTS: Two pigs in the control group died. The hyperosmotic infusion improved the circulatory performance significantly (p < 0.05). Thirty minutes after both bleeds the plasma catecholamine concentrations were increased by 10-15 times, but returned to the reference range in all groups 90 minutes after the hyperosmotic infusion. Two hours after the whole blood infusion the catecholamine concentrations of the treated animals were at baseline values, significantly lower than those of the controls. The corresponding urinary catecholamine concentrations of the controls were significantly increased. There were no differences between the two treatment groups. CONCLUSION: The catecholamine measurements indicate that there may possibly be protective renal excretion of excess shock-induced plasma catecholamines after acute haemorrhage.

Fatal myocardial depression and circulatory collapse associated with complement activation induced by plasma infusion in severe porcine sepsis.

We have previously reported that fresh frozen plasma (FFP) may induce a rapid irreversible shock when repeatedly infused in pigs challenged with Gram-negative sepsis. The aims of the present study were to elucidate the cardiovascular nature of the shock and determine the aetiologic role of tumour necrosis factor (TNF), complement activation and halothane anaesthesia. Three groups of anaesthetized piglets were inoculated with a lethal dose of live E. coli bacteria. Groups I (n = 8) and III (n = 8) were anaesthetized with halothane and group II (n = 8) with ketamine. Animals in groups I and II received repeated infusions of FFP, whereas animals in group III received repeated infusions of 7% albumin. Six animals in group I and four animals in group II died during the first plasma infusion. Survival time was significantly longer in group II (P = 0.04) compared to group I. No animals in group III died during the albumin infusions, and no adverse effects were observed during the infusions. In group I the plasma induced shock was characterized by abruptly falling mean arterial pressure, cardiac index, systemic vascular resistance index and left ventricular contractility. Concomitant increases were recorded in left ventricular filling pressure and central venous pressure. Group II demonstrated a similar, but delayed response. Plasma infusion was associated with a significant increase in terminal complement complex (TCC) (P < 0.03 in group I, P < 0.05 in group II) and depletion of serum ionized calcium. We conclude that FFP may induce fatal myocardial depression and circulatory collapse in severe sepsis. Complement activation may be of aetiologic importance.

The effects of plasma and albumin infusion on organ function and sepsis markers in experimental gram-negative sepsis.

To study the effects of early plasma versus albumin infusion on vital organ function and the appearance of central sepsis mediators in septic shock, three groups of anesthetized piglets (n = 28) were inoculated with live Eschericia coli. Group I received fresh frozen plasma, group II received albumin, whereas group III served as nontreated septic controls. Plasma-treated animals exhibited improved survival (p < .02) compared with controls, and improved organ function compared with both controls and albumin-treated animals. Plasma infusion was associated with increased levels of endotoxin (p < .02) and terminal complement complex (TCC) (p < .03), and persisting high levels of tumor necrosis factor (TNF). Following albumin infusion TNF levels decreased to baseline values (p < .01), whereas endotoxin and TCC levels did not change significantly. Our study shows a beneficial effect of early plasma infusion on survival and vital organ function in septic animals. The effect of plasma infusion on circulating levels of endotoxin, TNF, and TCC may be potentially deleterious in uncompensated stages of septic shock.

[Cystic lymphangioma of the mesentery]. / Cystisk lymfangiom i tynntarmskrøset.

Cystic lymphangioma of the mesentery is a rare congenital lesion with a relatively low growth potential. It is typically found in young adults, and thereby excluded from other, more aggressive lymphatic malformations seen in newborns. Symptoms of onset may be dramatic and sudden, but are often preceded by an interval of diffuse abdominal discomfort, possibly associated with loss of weight and a palpable abdominal mass. The multicystic architecture of the lesion is clearly visible on an abdominal CAT-scan and indicates the diagnosis. Percutaneous drainage of the cysts has neither diagnostic nor therapeutic effects. Radical excision of the expansion may include resection of the related intestinal segment. Lymphangioma of the mesentery is not malignant. We suggest an ultrasound follow-up six months after the intervention to establish whether the surgery has been successful.

Resuscitation of pigs with haemorrhagic shock by an intraosseous hyperosmotic solution and transfusion of autologous whole blood.

OBJECTIVE: To evaluate resuscitation after episodes of haemorrhagic shock by the combination of intraosseous infusion of a small volume of hyperosmotic fluid, followed by whole blood, in a standard experiment in pigs. DESIGN: Randomised open study. MATERIAL: 18 piglets. INTERVENTIONS: After a 60 minute period of stabilization all animals were bled to an arterial systolic pressure of 60 mm Hg. After 30 minutes 100 ml hyperosmotic fluid was given over a seven minute period into the tibial bone marrow (n = 6) or into an ear vein (n = 6). Ninety minutes later the animals were again bled to a systolic pressure of 60 mm Hg and 30 minutes after this they were treated by autologous blood transfusion either by intraosseous or intravenous infusion. Six animals acted as untreated controls. MAIN OUTCOME MEASURES: Changes in haemodynamic, haematological and biochemical variables. RESULTS: Two pigs in the control group died. There was no difference between the intraosseous and intravenous routes for the infusion of small volumes of hyperosmotic fluid or whole blood. There was a significant improvement in haemodynamic variables after resuscitation with intraosseous infusion of small volumes of hyperosmotic fluid (p < 0.05). CONCLUSION: Intraosseous infusions were easy to establish, and may be a useful method of resuscitation from haemorrhagic shock, particularly in children.