| 1. |
- Borg, T, et al.
(författare)
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A porcine model of early adult respiratory distress syndrome induced by endotoxaemia.
- 1985
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172 .- 1399-6576. ; 29:8, s. 814-30
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Tidskriftsartikel (refereegranskat)abstract
- To study the pathophysiology of early adult respiratory distress syndrome (ARDS) induced by sepsis, spontaneously breathing pigs under ketamine anaesthesia were investigated. Twenty animals were infused i.v. with E. coli endotoxin (10 micrograms . h-1 . kg-1) over 6 h, and ten control animals received physiological saline. In the controls, cardiac output (Qt) and O2 delivery decreased slightly. There were no changes in pulmonary gas exchange, pulmonary haemodynamics or extravascular lung water (EVLW). The polymorphonuclear (PMN) leucocyte count gradually increased, while the platelet count decreased slightly. Endotoxin infusion caused profound deterioration of pulmonary gas exchange, a marked rise in pulmonary vascular resistance (PVR) and a moderate increase in EVLW. The pulmonary dysfunction was not attributable to the pulmonary oedema per se, whereas a "dry" ventilation/perfusion inequality played an important role. The "responders" (peak venous admixture greater than 20%; n = 14) were characterized by higher Qt and lower PVR than the "non-responders". Qt declined progressively, especially in non-survivors. O2 delivery decreased considerably. Metabolic acidosis probably indicated oxygen deficit. Eleven of 20 animals died during the observation period. Mortality was related more to the imbalance between O2 delivery and oxygen demand than to the deterioration in pulmonary gas exchange. The PMN count decreased markedly while the gradual decline in platelet count was similar to that in the controls. Lung microscopy revealed PMN accumulation in the microvasculature, moderate interstitial oedema and microvascular blood stasis. Our porcine model, which closely mimics early ARDS in man, will be useful in further studies of the pathophysiological pathways and the treatment of this syndrome.
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| 2. |
- Borg, T, et al.
(författare)
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Prophylactic and delayed treatment with high-dose methylprednisolone in a porcine model of early ARDS induced by endotoxaemia.
- 1985
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172 .- 1399-6576. ; 29:8, s. 831-45
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Tidskriftsartikel (refereegranskat)abstract
- The effects of prophylactic and delayed treatment with high-dose methylprednisolone were evaluated in a porcine model of early adult respiratory distress syndrome induced by endotoxaemia. Spontaneously breathing pigs under ketamine anaesthesia were infused i.v. with E. coli endotoxin (10 micrograms . h-1 . kg-1) over 6h. Twenty animals received endotoxin without treatment. Eight animals were pretreated with methylprednisolone i.v., 60 mg . kg-1, followed by an i.v. infusion at a rate of 10 mg . h-1 . kg-1. Ten animals received the same dosage of methylprednisolone beginning 2 h after the start of endotoxin infusion. Pretreatment with methylprednisolone prevented the endotoxin-induced impairment in pulmonary gas exchange and the development of pulmonary oedema. The pulmonary hypertension was counteracted. Cardiac output (Qt) and O2 delivery were improved. Mean arterial blood pressure (MAP) increased and was higher than in the untreated endotoxin group. The profound fall in PMN count was inhibited, while the accumulation of these cells in the lung was still substantial. Survival was improved. Delayed methylprednisolone treatment prevented further deterioration in pulmonary gas exchange and tended to restore it towards baseline. The pulmonary oedema and pulmonary hypertension were reduced. Qt and O2 delivery did not improve. MAP was higher than in the untreated endotoxin group towards the end of the observation period. The decline in PMN count and the pulmonary accumulation of these cells were not significantly influenced. Survival was improved. These results indicate that high-dose methylprednisolone, when given early in the course of sepsis, might be of clinical value in prevention of the devastating pulmonary and circulatory complications of this disease.
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| 3. |
- Borg, T, et al.
(författare)
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Prophylactic and delayed treatment with indomethacin in a porcine model of early adult respiratory distress syndrome induced by endotoxaemia.
- 1986
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172 .- 1399-6576. ; 30:1, s. 47-59
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Tidskriftsartikel (refereegranskat)abstract
- The effects of prophylactic and delayed treatment with indomethacin were evaluated in a porcine model of early adult respiratory distress syndrome (ARDS) induced by endotoxaemia. Spontaneously breathing pigs under ketamine anaesthesia were infused i.v. with E. coli endotoxin (10 micrograms . h-1 . kg-1) over 6 h. Twenty animals received endotoxin without treatment. Eight animals were pretreated with indomethacin i.v., 5 mg . kg-1 in 30 min, followed by further infusion at a rate of 2 mg . h-1 . kg-1. Ten animals received the same dosage of indomethacin beginning 2 h after the start of endotoxin infusion. Pretreatment with indomethacin inhibited the endotoxin-induced impairment in pulmonary gas exchange, but did not prevent pulmonary oedema. The pulmonary hypertension was counteracted. Oxygen delivery did not improve, because of a marked reduction in cardiac output (Qt). Systemic vascular resistance (SVR) increased markedly, and mean arterial pressure (MAP) was higher. Survival was improved. Delayed indomethacin treatment prevented a further deterioration in pulmonary gas exchange and restored it towards the baseline level. The pulmonary oedema was not counteracted, while the pulmonary hypertension was reduced. O2 delivery was not restored, owing to the greater decrease in Qt compared with the untreated endotoxin group. SVR increased considerably, and MAP was better maintained. Survival was not improved. These results indicate that cyclo-oxygenase inhibitors might benefit pulmonary gas exchange in human ARDS. Drugs which interfere with arachidonate metabolism will probably be of great importance in the prophylaxis, in particular, and also in the treatment of ARDS.
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| 4. |
- Borg, T, et al.
(författare)
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The role of polymorphonuclear leucocytes in the pulmonary dysfunction induced by complement activation.
- 1985
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172 .- 1399-6576. ; 29:2, s. 231-40
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Tidskriftsartikel (refereegranskat)abstract
- To determine the role of polymorphonuclear leucocytes (PMNs) in the pulmonary reaction induced by complement activation, pigs were infused with complement-activated plasma (CAP), cell-free supernatant from PMNs activated in vitro, or washed PMN aggregates produced in vitro. Infusion of CAP resulted in transient peripheral leucopenia, a reversible rise in pulmonary vascular resistance (PVR) and decreased arterial oxygen tension (PaO2). Indomethacin did not influence the CAP-induced drop in PMN count or the accumulation of PMNs in the lung, but significantly counteracted the rise in PVR and fall in PaO2. Antihistamines did not prevent the cellular or pulmonary reactions to CAP infusion. Methylprednisolone did not inhibit the decrease in PMN count, but modified the pulmonary reaction to CAP, although it did not prevent the rise in PVR to the same extent as indomethacin; it counteracted the fall in PaO2. Infusion of supernatant from activated PMNs did not influence the PMN count, but caused a reversible increase in PVR and a drop in PaO2. Indomethacin counteracted the pulmonary reaction to this infusion. Infusion of washed PMN aggregates did not result in any cellular or physiological changes. These findings suggest that the pulmonary reaction induced by complement activation is mediated by humoral components generated and/or released during activation of PMNs. Arachidonic acid metabolites play an important role and it is likely that substance(s) released from activated PMNs trigger prostanoid synthesis in other cells. It is conceivable, however, that PMNs exposed to activated complement factors also directly synthesize and release arachidonic acid metabolites.
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| 5. |
- Olsson, H., et al.
(författare)
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A biological marker, strongly associated with early oral contraceptive use, for the selection of a high risk group for premenopausal breast cancer
- 1986
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Ingår i: Medical Oncology and Tumor Pharmacotherapy. - 0736-0118. ; 3:2, s. 77-81
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Tidskriftsartikel (refereegranskat)abstract
- In a population-based group of women, consecutively diagnosed, with premenopausal breast cancer there was a significant correlation between tumour size and plasma prolactin (r=0.30;P<0.004). The concentration of estrogen receptor was negatively correlated to tumour size (r=-0.17;P<0.09). There were no substantial correlations between tumour size and progesterone receptor, plasma progesterone or estradiol. Adjustments for menstrual cycle day and age did not alter the above findings. The ratio of plasma prolactin and estrogen receptor was significantly greater (P<0.037) for the group of the patients that had started using oral contraceptives before the age of 20 as compared with the other patients. Consequently, the tumour size was significantly greater in the group of early users (P<0.003). The findings indicate that breast tumours developing in previous early users of oral contraceptives have a low estrogen receptor concentration, while these patients have plasma prolactin. The tumour size is greater in early users indicating a poorer prognosis than other women with breast cancer. As early use of oral contraceptives increases, breast cancer risk and a high ratio of plasma prolactin and estrogen receptor concentration of the primary tumour characterize early oral contraceptive users the ratio may be a valuable marker for the breast cancer risk.
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| 6. |
- Olsson, H., et al.
(författare)
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Early oral contraceptive use as a prognostic factor in breast cancer
- 1988
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Ingår i: Anticancer research. - 0250-7005. ; 8:1, s. 29-32
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Tidskriftsartikel (refereegranskat)abstract
- The survival of 193 premenopausal breast cancer patients was investigated in relation to their history of early use of oral contraceptives. The women were born in 1939 or later and diagnosed in the southern health care region of Sweden. Women, who had started their oral contraceptive use (OC-use) before 20 years of age had a significantly lower survival rate as compared with those who had never used OC and late users (p = 0.02 and = 0.04 respectively, generalized Wilcoxon test). For women who started OC-use between 20 to 25 years of age, a tendency for a shorter survival was seen in comparison with women who had never used OC (p = 0.18). For all patients simultaneously, the relative risk adjusted for age at diagnosis increased for earlier OC-start. When only stages II and III were considered in a stratified multivariate model, a signficantly elevated risk was seen for early users of OC irrespective of age or of adjuvant treatment given. The estrogen and progesterone receptor concentrations of the primary tumor were significantly lower among early users (p = 0.001 and p = 0.05 respectively).
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| 7. |
- Olsson, H., et al.
(författare)
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Permanent alterations induced in plasma prolactin and estrogen receptor concentration in benign and malignant tissue of women who started oral contraceptive use at an early age
- 1987
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Ingår i: Anticancer research. - 0250-7005. ; 7:4 B, s. 853-856
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Tidskriftsartikel (refereegranskat)abstract
- In 65 young women undergoing curettage for benign utrine disorders a signicicant relationship was found between early oral contraceptive use (starting age<25 years) and a high ratio of ln plasma prolactin versus ln estrogen receptor concentration of the uterine mucosae (p<0.047, Mann-Whitneys U-test). Year of birth, age at menarche, age at first full term pregnancy, parity, menstrual cycle phase and duration of oral contraceptive use could not explain the results. Because similar results have previously been found for breast cancer patients using plasma prolactin and breast tumour estrogen receptor concentration, the findings indicate that early oral contraceptive use permanently alters plasma prolactin levels and estrogen receptor concentration, both in benign uterine tissue and in malignant breast tumours.
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