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- Rydvall, A., et al.
(författare)
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Plasma cortisol is often decreased in patients treated in an intensive care unit
- 2000
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Ingår i: Intensive Care Med. ; 26:5, s. 545-51
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the prevalence of adrenal hypofunction, as assessed by plasma cortisol (p-cortisol) and its relationship to clinical events. DESIGN: Prospective, consecutive. SETTING: General intensive care unit in a university hospital. PATIENTS: Fifty-five patients (34 men and 21 women) were studied (surgery 40 patients, hemodialysis 5, ventilator treatment 45, sepsis 21). METHODS: Morning basal levels of p-cortisol were determined. Previous reports define adrenal insufficiency to be present if p-cortisol under stressful conditions is lower than either 400 or 500 nmol/l. The tetracosactoid test (250 microg Synacthen) was performed in 16 patients and urinary 24-h excretion of cortisol in 24 (none on corticosteroid treatment). RESULTS: Median p-cortisol was 550 nmol/l (range 20-1764). In 36% of patients p-cortisol was lower than 400 nmol/l and in 47% lower than 500 nmol/l. There was a significantly increased probability (P < 0.05) of p-cortisol being below 400 nmol/l in patients admitted due to trauma or cerebral disorder and in patients on ventilator therapy or on mannitol. Thirty minutes after tetracosactoid administration p-cortisol response was lower than 200 nmol/l in 56% of the patients. CONCLUSIONS: Several patients had low p-cortisol and attenuated responses to tetracosactoid, indicative of adrenal insufficiency. There seem to be certain risk factors for adrenal hypofunction which may justify more frequent use of physiological doses of corticosteroid in selected patients.
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- Nicholson, L B, et al.
(författare)
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Monoclonal antibodies to the human TSH receptor: epitope mapping and binding to the native receptor on the basolateral plasma membrane of thyroid follicular cells.
- 1996
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Ingår i: Journal of molecular endocrinology. - 0952-5041. ; 16:2, s. 159-70
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Tidskriftsartikel (refereegranskat)abstract
- We have characterized four murine monoclonal antibodies (mAbs) to the extracellular domain of the human TSH receptor (TSH-R.E), the target autoantigen of Graves' disease. Recombinant TSH-R.E used as immunogen, was produced in E. coli as a fusion protein with glutathione-S-transferase or in a baculovirus-insect cell system, as a non-fusion glycoprotein. To increase the epitope specificity of the mAbs, two different strains of mice (H-2(b) and H-2(d)) were immunized. The epitopes recognized by the mAbs were characterized by immunoblotting with various recombinant constructs of TSH-R.E and by binding to overlapping synthetic peptides of the receptor. The four IgG mAbs characterized recognized epitopes localized to different regions on the TSH-R.E; amino acids 22-35 (A1O and A11, both IgG2b from H-2(b) animals), amino acids 402-415 (A7, IgG2b from H-2(b) animals) and amino acids 147-228 (A9, IgG1 from H-2(d) animals). Immunolocalization studies showed that mAb A9 recognized TSH-R.E on unfixed cryostat sections, where binding was localized to the basolateral plasma membrane of thyroid follicular cells, suggesting that this antibody reacts with the native receptor on thyroid cells. The binding of the mAbs A7, A10 and A11 was also restricted to the basal surface of thyroid cells, but only after acetone fixation of the sections, implying that the epitopes recognized on the amino and carboxyl terminus of the extracellular region of the receptor are not accessible on the native molecule. None of the mAbs stimulated cyclic AMP responses in COS-7 cells transiently transfected with full-length functioning TSH-R.E, whilst weak inhibition of binding of radiolabelled TSH to porcine membranes in a radioreceptor assay was apparent with mAb A10 and A11, but only at high concentrations of IgG. The ability of mAb A9 to bind to the native receptor without stimulating activity or inhibition of TSH binding suggests that antibody can bind to the central region of the TSH-R.E without perturbing receptor function. The availability of mAbs that recognize epitopes on different regions of the extracellular domain of TSH-R will lead to a better understanding of the autoantigenic regions on TSH-R implicated in disease activity.
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- Stegmayr, B. G., et al.
(författare)
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Plasma exchange as rescue therapy in multiple organ failure including acute renal failure
- 2003
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Ingår i: Crit Care Med. ; 31:6, s. 1730-6
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To describe the outcome of using a rescue therapy including plasma exchange given to patients with a progressive acute disseminated intravascular coagulation and multiple organ dysfunction syndrome. STUDY DESIGN: Retrospective study. SETTING: University and county hospital. PATIENTS: Included were 76 consecutive patients (41 men and 35 women) treated with plasma exchange as rescue therapy besides optimal conventional therapy during a progressive course of disseminated intravascular coagulation and multiple organ dysfunction syndrome, including acute renal failure. Of the 76 patients, 66% needed dialysis. The distribution was hemodialysis in 76%, continuous arteriovenous hemofiltration in 36%, continuous venovenous hemodialysis in 12%, and peritoneal dialysis in 24%. The median organ-failure score was 5 (range, 1-6). Seventy-two percent required mechanical ventilation; septic shock was present in 88%. The median septic shock score was 4 (range, 2-4). Nine patients had another reason than sepsis for the multiple organ dysfunction syndrome. INTERVENTION: Plasma exchange (centrifugation technique) was performed until disseminated intravascular coagulation was reversed (median, two times; range, 1-14). Besides antibiotics and fluid administration, most patients received heparin or low molecular weight heparin (77%), steroids (87%), and inotropes (88%). More than one vasoactive drug was used in 57% of the patients. MEASUREMENTS AND MAIN RESULTS: Eighty-two percent of the patients survived and could leave the hospital. The previously observed survival rates by others for this category of patients would be <20%, and thus, the outcome in this study is significantly better. CONCLUSION: Plasma exchange using plasma as replacement may, in addition to conventional intensive care, help to reverse severe progressive disseminated intravascular coagulation and multiple organ dysfunction syndrome and improve survival.
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