Biomedical subjects
A Waage
Publications and source records attributed to A Waage.
[Tumor necrosis factor. A mediator in septic shock].
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Interleukin 1 potentiates the lethal effect of tumor necrosis factor alpha/cachectin in mice.
Human rIL-1 alpha and human rIL-1 beta were examined for their ability to potentiate the lethal and hypothermic effects of mouse rTNF-alpha in mice. The LD50 of rTNF-alpha was 1.5 micrograms/mouse, whereas the LD50 of rTNF-alpha was reduced to 0.4 micrograms/mouse and 0.5 micrograms/mouse when rTNF-alpha was administered in combination with a nonlethal dose of rIL-1 alpha or rIL-1 beta, respectively. A similar rTNF-alpha enhancing effect of the rIL-1 was observed on the temperature response. The results show that the rIL-1 markedly potentiate the effects of rTNF-alpha on lethality and temperature in mice, and support our suggestion that TNF-alpha and IL-1 may have synergistic lethal effect in human septic shock.
The involvement of tumor necrosis factor-alpha (TNF-alpha) in immunomodulation and in septic shock.
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Glucocorticoids suppress the production of tumour necrosis factor by lipopolysaccharide-stimulated human monocytes.
We have investigated the modulating effect of steroids on the in vitro production of tumour necrosis factor (TNF) by lipopolysaccharide (LPS)-stimulated human monocytes. Dexamethasone, at concentrations ranging from 10(-8) to 10(-6) M, and cortisol, at concentrations 10(-7) and 10(-6) M, suppressed the TNF production in a dose-dependent manner. The highest concentrations of dexamethasone or cortisol reduced the TNF production to 21 +/- 2% and 48 +/- 8% of the control value, respectively. The effect of dexamethasone was time dependent, and an incubation time of 48 hr was required to reduce the TNF production to 21% of control. The effect of dexamethasone decreased when the incubation time became shorter, and the mean TNF production ranged from 49% to 72% of control when dexamethasone was added later than 8 hr before LPS addition, at the time of LPS addition, or within 1 hr after LPS addition. The magnitude of the TNF-suppressing effect of dexamethasone varied greatly from donor to donor. Only the glucocorticoids, and not the sex steroids or the mineralocorticoids, significantly reduced the TNF production.
Association between tumour necrosis factor in serum and fatal outcome in patients with meningococcal disease.
Serum samples taken on admission from 79 patients with meningococcal meningitis, septicaemia, or both, were examined in a highly sensitive bioassay for tumour necrosis factor (TNF). TNF was detected in samples from 10 of 11 patients who died but from only 8 of 68 survivors. All 5 patients with serum TNF levels over 440 units/ml (corresponding to 0.1 ng/ml recombinant TNF) died.
[Polycythemia and smoking].
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[Nutritional status and energy intake in patients admitted to internal medicine units].
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Production and clearance of tumor necrosis factor in rats exposed to endotoxin and dexamethasone.
The production and clearance of tumor necrosis factor (TNF) in relation to endotoxinemia was studied by the injection of lipopolysaccharide (LPS) in rats. TNF was released into the circulation as a burst when the serum concentration of LPS was rapidly or gradually increased. The maximum concentration of TNF in serum was attained 60 to 90 min after the injection of LPS. TNF was eliminated from the serum according to a first-order kinetics; the half-life was calculated to be 27 +/- 7 min. No additional release of TNF could be evoked by a persistent high level of LPS. When two LPS injections were given within 3 days, the peak concentration of TNF detected after the second injection was 15% of the concentration detected after the first injection. The results indicate that if TNF is a mediator of septic shock, its role is restricted to the initial phase after the appearance of endotoxin in the circulation. Treatment of the rats with dexamethasone (0.5-2.0 micrograms/g) reduced the LPS-induced peak concentrations of TNF in serum by 70-90%. Maximal suppression of the TNF release was observed when dexamethasone was given 5 hr or more prior to LPS, but was gradually lost at shorter intervals.
Aclarubicin in the treatment of relapsed or resistant acute myelogenous leukaemia: a phase II trial.
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[Sarcoidosis of the nervous system].
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[Myelodysplastic syndrome and myelogenous leukemia. Treatment with low-dose cytarabine].
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Detection of tumour necrosis factor-like cytotoxicity in serum from patients with septicaemia but not from untreated cancer patients.
With a bioassay sensitive for recombinant tumour necrosis factor at a concentration of 10(-4) ng/ml, we were able to detect tumour necrosis factor-like cytotoxicity in serum from three patients in the initial phase of septicaemia. The cytotoxic activity corresponded to a concentration of recombinant tumour necrosis factor of 2 X 10(-2)-3 X 10(-3) ng/ml serum. The concentration in cerebrospinal fluid was estimated to be three times higher than in serum. In 23 untreated patients with malignant disease of varying origin and stage, including two patients with severe cachexia, we were not able to detect tumour necrosis factor-like cytotoxicity.
Thrombotic thrombocytopenic purpura in 2 siblings: defective platelet function and plasma factor deficiency occurring simultaneously.
In 2 siblings with recurring attacks of thrombotic thrombocytopenic purpura, platelet aggregation was found to be decreased during attacks. In contrast with reported observations in other patients, aggregation was found decreased also in symptom-free periods. ATP/ADP ratio in platelet rich plasma was normal. The cause of decreased aggregation was not uraemia, alcohol or drugs. In a healthy sister, platelet aggregation induced by ADP was subnormal. The attacks in 1 of the patients responded to infusion of fresh frozen plasma.
Chronic granulocytic leukaemia in accelerated stage treated with low dose cytosine arabinoside.
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[Behavior of hypertension and cardiovascular findings in hypertension within an observation period of 10 years (the Wurzen study 1961-1971)].
In concert with literary data during a mass X-ray examination in 1961 we established in 5,517 men of the district Wurzen a frequency of hypertension of 13.6% and in 1971 in the same group of test persons a frequency of hypertension of 19.4%. The percentage of the pathological cardiovascular X-ray findings was in normotonus 10.4% in 1961 and 11.2% in 1971, in hypertension 22.3% in 1961 and 27.5% in 1971. The dependence on the age of the test persons, on the degree of severity of hypertension, and particularly on the duration of the hypertension is clear. For prevention of a hypertensive heart disease the early recognition of a hypertension and an early therapy are necessary. On the basis of our studies the making of cardiovascular X-ray findings from photofluorograms is not suitable as screening test for the hypertension. The value of blood pressure controls in mass X-ray examinations must be emphasized. Important is the collection of cardiovascular X-ray findings from photofluorograms of the thorax for the establishment of a hypertensive heart disease, of not recognized vitia and age-conditioned cardiac and vascular changes. It implies an optimum use of the material collected in the mass X-ray examination.
Bile leak after cholecystectomy significance and treatment: results from the National Norwegian Cholecystectomy Registry.
From April 1993 to July 1995, altogether 3860 procedures were enrolled in the Norwegian National Cholecystectomy Registry (NNCR), 777 (20.2%) being open operations. 3083 (79.8%) were initiated laparoscopically, 313 (10.2%) of these converted to open technique. Mortality within 30 days after open cholecystectomy was 1.9%, after a converted procedure 1.0% and 0.14% after laparoscopic cholecystectomy (p<0.01). According to the intention to treat principle, converted procedures should be included in the laparoscopic group. This gives seven deaths after 3083 procedures, i.e. 0.23%. Postoperative death still occurs approximately 10 times more frequently after open cholecystectomy (p<0.01). However, this is partly due to selection of high risk cases to open technique. Postoperative bile leak was observed in 25 patients (0.9%) in the laparoscopic, 13 (4.2%) in the converted and 19 (2.4%) in the open group. Bile leak contributed significantly to serious complications. 37 major problems were observed in 25 of the patients (44%). Five patients died (8.8%). Among the 57 bile leak patients, common bile duct (CBD) injury was found in 13 (22.8%). Additional 19 CBD injuries occurred, presenting with other symptoms such as icterus, or being recognised during the first operation. The frequency of CBD injury in the laparoscopic group was 14 (0.5%), in the converted group 12 (3.8%) and in the open group 6 (0.8%). None of the patients with CBD injury underwent intraoperative cholangiography. The present results firstly show that open cholecystectomy cannot be considered a safe procedure for high risk patients, secondly, that postoperative bile leak contributes significantly to postoperative mortality and hence is a serious condition generating from CBD injury in about 1/5 of all cases.