| 1. |
- Carling, Tobias, et al.
(författare)
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Familial hypercalcemia and hypercalciuria caused by a novel mutation in the cytoplasmic tail of the calcium receptor
- 2000
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - 0021-972X .- 1945-7197. ; 85:5, s. 2042-7
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Tidskriftsartikel (refereegranskat)abstract
- Familial hyperparathyroidism (HPT), characterized by hypercalcemia and hypercalciuria, and familial benign hypocalciuric hypercalcemia (FHH) are the most common causes of hereditary hypercalcemia. The calcium-sensing receptor (CaR) regulates PTH secretion and renal calcium excretion. Heterozygous inactivating mutations of the gene cause FHH, whereas CaR gene mutations have not been demonstrated in HPT. In a kindred with 20 affected individuals, the hypercalcemic disorder segregated with inappropriately higher serum PTH and magnesium levels and urinary calcium levels than in unaffected members. Subtotal parathyroidectomy revealed parathyroid gland hyperplasia/adenoma and corrected the biochemical signs of the disorder in seven of nine individuals. Linkage analysis mapped the condition to markers flanking the CaR gene on chromosome 3q. Sequence analysis revealed a mutation changing phenylalanine to leucine at codon 881 of the CaR gene, representing the first identified point mutation located within the cytoplasmic tail of the CaR. A construct of the mutant receptor (F881L) was expressed in human embryonic kidney cells (HEK 293), and demonstrated a right-shifted dose-response relationship between the extracellular and intracellular calcium concentrations. The hypercalcemic disorder of the present family is caused by an inactivating point mutation in the cytoplasmic tail of the CaR and displays clinical characteristics atypical of FHH and primary HPT.
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| 2. |
- Johansson, Jakob, et al.
(författare)
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Antithrombin administration during experimental cardiopulmonary resuscitation
- 2004
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 62:1, s. 71-78
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether antithrombin (AT) administration during cardiopulmonary resuscitation (CPR) increased cerebral circulation and reduced reperfusion injury. METHODS: Ventricular fibrillation was induced in 24 anaesthetised pigs. After a 5-min non-intervention interval, CPR was started. The animals were randomised into two groups. The treatment group received AT (250 U/kg) and the control group received placebo, after 7 min of CPR. Defibrillation was attempted after 9 min of CPR. If restoration of spontaneous circulation (ROSC) was achieved, the animals were observed for 4 h. Cortical cerebral blood flow was measured using laser-Doppler flowmetry. Cerebral oxygen extraction was calculated to reflect the relation between global cerebral circulation and oxygen demand. Measurements of eicosanoids (8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha)), AT, thrombin-antithrombin complex (TAT) and soluble fibrin in jugular bulb plasma were performed to detect any signs of cerebral oxidative injury, inflammation and coagulation. RESULTS: There was no difference between the groups in cortical cerebral blood flow, cerebral oxygen extraction, or levels of eicosanoids, TAT or soluble fibrin in jugular bulb plasma after ROSC. In the control group reduction of AT began 15 min after ROSC and continued throughout the entire observation period (P < 0.05). Eicosanoids and TAT were increased compared to baseline in all animals (P < 0.01). CONCLUSIONS: In this experimental model of CPR, AT administration did not increase cerebral circulation or reduce reperfusion injury after ROSC.
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| 3. |
- Johansson, Jakob, et al.
(författare)
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Antithrombin reduction after experimental cardiopulmonary resuscitation
- 2003
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Ingår i: Resuscitation. - 0300-9572 .- 1873-1570. ; 59:2, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether activation of coagulation and inflammation during cardiac arrest results in a reduction of antithrombin (AT) and an increase in thrombin-antithrombin (TAT) complex during reperfusion.METHODS: Ventricular fibrillation (VF) was induced in ten anaesthetized pigs. After a 5-min non-intervention interval, closed-chest cardiopulmonary resuscitation (CPR) was performed for 9 min before defibrillation was attempted. If restoration of spontaneous circulation (ROSC) was achieved, the animals were observed for 4 h and repeated blood samples were taken for assay of AT, TAT and eicosanoids (8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha)).RESULTS: AT began to decrease 15 min after ROSC and the reduction continued throughout the observation period (P<0.05). The lowest mean value (79%) occurred 60 min after ROSC. The TAT level was increased during the first 3 h after ROSC (P<0.05), indicating thrombin generation. The eicosanoids were increased throughout the observation period (P<0.05).CONCLUSIONS: AT is reduced and TAT and eicosanoids are increased after cardiac arrest, indicating activation of coagulation and inflammation.
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