Use of abciximab prior to primary angioplasty in STEMI results in early recanalization of the infarct-related artery and improved myocardial tissue reperfusion - results of the Austrian multi-centre randomized ReoPro-BRIDGING Study.

AIMS: The aim of the ReoPro-BRIDGING Austrian multi-centre study was to investigate the effects of abciximab (ReoPro) on early reperfusion in ST-elevation myocardial infarction prior to or during primary percutaneous coronary angioplasty (pPCI). METHODS AND RESULTS: Fifty-five patients with STEMI were randomized either to start abciximab (0.25 mg/kg bolus followed by 10 microg/min infusion) during the organization phase for pPCI (Group 1, n=28) or immediately before pPCI (Group 2, n=27). The time between first bolus of abciximab and first balloon inflation of pPCI was 83+/-18 vs 21+/-13 min in Group 1 vs 2. The pre-pPCI ST-segment resolution (55+/-21.4% vs 42.4+/-18.2%, p=0.005), TIMI flow grade 3 (29% vs 7%, p=0.042), corrected TIMI frame count (58.4+/-32.7 vs 78.9+/-28.4 frame, p=0.018) %diameter stenosis (76.3 /63.5-100/ vs 100 /73.5-100/; median /interquartile range/, p=0.023), were significantly higher in Group 1 vs Group 2. Quantitative myocardial dye intensity measurement revealed a significantly higher grade of myocardial tissue perfusion (1 /0-9.25/ vs 0 /0-3.0/ grey pixel unit, p=0.048) in Group 1 before pPCI. Rapid release of cardiac enzymes was observed in Group 1 as compared with Group 2: rate of rise of CK was 210+/-209 vs 97+/-95 U/l/h (p=0.015). QRS score indicated a smaller infarct size in Group 1 (4.8+/-3.8 vs 7.6+/-3.5, p=0.011) on day 7. CONCLUSION: The use of abciximab in the organization phase for pPCI results in signs of early recanalization of the infarct-related artery and a subsequent improved myocardial tissue reperfusion.     

Effect of Ethanol Administration and Withdrawal on Serotonin Receptor Subtypes and Receptor-Mediated Phosphoinositide Hydrolysis in Rat Brain

The effect of short-term (15 days) and long-term (60 days) ethanol treatment and withdrawal on agonist-stimulated phosphoinositide (Pl) hydrolysis, serotonin receptor subtypes (5HT1A and 5HT2), and alpha 1-adrenergic receptors were studied in rat cerebral cortex. Short-term ethanol treatment had no significant effect on serotonin (5HT), norepinephrine (NE), and calcium ionophore (A23187)-stimulated [3H]-inositol-1-phosphate ([3H]-IP1) formation and 5-HT2 receptors as measured by 125I-lysergic acid diethylamide (125I-LSD) binding, in rat cerebral cortex. However, 15 days of ethanol treatment, followed by 24 hr of withdrawal resulted in a decrease in Bmax of 125I-LSD binding without significant change in KD, as well as a decrease in 5HT-stimulated [3H]-IP1 formation in rat cerebral cortex. 5HT1A and alpha 1-adrenergic receptors were determined by using [3H]-8-hydroxy-2-(di-N-propylamino)tetralin and [3H]-prazosin as radioligand, respectively. We also observed that long-term ethanol treatment had no significant effect on Bmax and KD of 5HT2, 5HT1A, and alpha 1-adrenergic receptors, as well as NE and A23187-stimulated [3H]-IP1 formation, but significantly decreased the 5HT-stimulated [3H]-IP1 formation in rat cerebral cortex. It is possible that a decrease in 5HT-induced PI turnover after long-term ethanol exposure may be due to a decrease in coupling of 5HT2 receptors to G protein or PLC enzyme, whereas the decrease in 5HT-induced PI turnover after withdrawal may be due to a decrease in functional 5HT2 receptor number.     

Serum growth hormone in patients with carcinoid tumours; basal levels and response to glucose and thyrotrophin releasing hormone

The regulation of serum growth hormone was studied in 33 consecutive patients with carcinoid tumours; both diurnal serum GH and GH responses to an i.v. glucose load and TRH were assessed. Seventeen of the patients (52%) showed disturbed regulation of serum GH and 10 had at least two abnormal tests. Four patients had clinically overt acromegaly. The diurnal mean serum GH levels were higher (P less than 0.001) in patients with carcinoid tumours than in control subjects and more than one third (41%) had levels in a range similar to that of acromegalic patients without carcinoid tumours. The disturbance in serum GH regulation might have been caused in some patient by tumour secreted growth hormone releasing factor(s) which act directly on pituitary somatotrophs, but other tumour-related non-specific stimulation must be considered. Carcinoid tumours should be considered in the aetiology of acromegaly.     

Prolactin levels in the insulin tolerance test with and without pre-treatment with dexamethasone

The serum prolactin response to insulin-induced hypoglycaemia was studied in 20 healthy volunteers. The results of insulin tolerance tests performed after pre-treatment with dexamethasone in a dose of 0.5 mg (0.5-DEX-ITT) and 1.0 mg (1.0-DEX-ITT) were compared with those of a similar control insulin tolerance test (ITT). The serum prolactin levels increased in all but 3 ITT's. In the ITT and 0.5-DEX-ITT the prolactin responses were significantly greater in women than in men. After pretreatment with dexamethasone the basal serum prolactin levels and the prolactin response to hypoglycaemia were significantly decreased compared with those in the ITT. The prolactin response both to insulin-induced hypoglycaemia and to dexamethasone showed such a large individual variation that this type of response seems unsuitable for evaluation of the hypothalamo-pituitary function.     

Physiological response to phlebotomies for autologous transfusion at elective hip-joint surgery

In order to study the physiological response to phlebotomies for autotransfusion, an autotransfusion program was designed for 10 patients undergoing hip-joint replacement surgery for arthrosis. 4 phlebotomies of 450 ml each were performed within 12 days. Blood samples were taken immediately before phlebotomy for blood hemoglobin (Hb), serum erythropoietin (Epo), reticulocyte count (ret) and erythrocyte 2,3-diphosphoglycerate (DPG). All 4 phlebotomies could be performed in 9/10 patients, and only 1 patient had significant symptoms (fatigue). The operation was performed 2 weeks after the last phlebotomy. None of the patients had recovered the initial Hb level at operation (24.8 +/- 9 per liter lower than initially), and they were all even more anemic after the operation (36.8 +/- 16.9 g/l lower than initially). Serum Epo increased from 13.6 +/- 7.2 IU to 30.6 +/- 12.2 (SD) IU per liter, and reticulocyte counts increased to a maximum of 3.68 +/- 1.69%. DPG increased in all patients except the one who had significant fatigue. It is concluded that the patients tolerated the phlebotomy program well but that a significant anemia developed. The compensatory increase in erythropoietin and reticulocyte count, adequate for this degree of anemia, was small compared to the increase seen at more severe anemia, indicating that there may be a role for pharmacological stimulation of erythropoiesis in blood predeposit programs.     

Effect of chronic daily oral administration of 17βoestradiol and norethisterone on the isoforms of serum gonadotrophins in post-menopausal women

OBJECTIVE Chronic treatment with 17βoestradlol (E₂Implants has been found to counteract the formation of more acidic isoforms of the gonadotrophins in post-menopausal women. Oral medication with an oestrogen in combination with a progestagen is a common hormone replacement therapy (HRT) in post-menopausal women. The present study investigated the effect of such a therapy on the concentration and charge of the gonadotrophin isoforms in serum. DESIGN Serum samples were obtained from 20 post-menopausal women, mean age 60 years (range 50–72 years), treated with continuous dally oral medication of 2 mg E₂ combined with 1 mg norethisterone acetate (NETA). FSH, LH and E₂ in the serum was measured with fluoroimmunoassays. The median charge and charge heterogeneity of the FSH and LH isoforms were determined for each serum by electrophoresis in 0·1% agarose suspension. Sera from 20 post-menopausal women without a history of HRT served as controls. The results were compared with those from previous studies on post-menopausal women treated with E₂ Implants and on women with normal menstrual cycles. RESULTS The E₂ level in the oral-E₂+ NETA treated women was 198-610 pmol/l, within the range expected during the mid-luteal phase of the normal menstrual cycle and similar to that of the group of women with an E₂ Implant. The mean LH level was similar to that of the luteal phase of the cycle and significantly lower than that of the controls (P < 0·001), the E₂ Implant group (P < 0·001) and at the follicular phase of the cycle (P < 0·01). The mean FSH level was slmllar to that of the folllcular phase and the E₂ implant group but lower than that of the controls (P < 0·001) and higher than at the luteal phase of the cycle (P < 0·01). The mean values for median charge of both FSH and LH were less acidic than those of the controls (P < 0·001) but more acidic than those for the E₂ Implant group (P < 0·01; P < 0·001) and for different phases of the menstrual cycle (P < 0·05; P < 0·001). The mean degree of charge heterogeneity of FSH was larger (P < 0·01), while that of LH was smaller (P < 0·01), than for the controls. The mean concentrations of SHBG in the oral E₂+ NETA group, the E₂ implant group and the controls were similar. CONCLUSION Chronic oral therapy with 2mg 17β oestradiol combined with 1 mg norethisterone in post-menopausal women efficiently decreased the serum gonadotrophin levels but only partly counteracted the formation of the more acidic isoforms of FSH and LH after menopause. The differences in the charge for both FSH and LH between the E₂ Implant and the oral E₂+ NETA treated groups may be due to the differences in route of administration of E₁ or to the effect of norethisterone or both.     

Facilitation of primary PCI with ReoPro: reply

The corrected TIMI frame count (CTFC) method has been prospectivelyvalidated as providing independent risk stratification aboveand beyond the conventional TIMI flow grades.¹ In myocardialinfarction studies including patients with an occluded infarct-relatedartery, a frame count of 100, a value that is     

Early follicular phase luteinizing hormone-releasing hormone agonist administration - effects on follicular maturation and corpus luteum function in women

The potent luteinizing hormone-releasing hormone (LRH) agonist D-Ser(TBU)6-EA10-LRH was administered in a daily subcutaneous dose of 5 or 25 microgram for 1, 3 or 5 consecutive days to twelve regularly menstruating women in the early follicular phase of the menstrual cycle in an attempt to disturb follicular maturation and induce luteolysis. The treatment was monitored by clinical examinations, basal body temperature recordings, bleeding patterns and frequently taken peripheral venous blood samples for analyses of gonadotropins and ovarian steroids. The luteal phase during the LRH agonist treatment cycles did not differ in length from that of the control cycles before and after the treatment (p greater than 0.05). The maximal progesterone concentration during the luteal phase exceeded 32 nmol/l in all but one of the treatment cycles. The follicular phase of the treatment cycle was prolonged in comparison with that of the control cycles (p less than 0.01). Thus, administration of high doses of a superactive LRH agonist during the early follicular phase of the menstrual cycle prolonged the follicular phase and postponed ovulation but did not interfere with corpus luteum function in normally ovulating women.     

The early serum insulin response to intravenous glucose in patients with decreased glucose tolerance and in subjects with a familial history of diabetes mellitus.

Intravenous glucose tolerance tests with estimations of K values and measurements of serum insulin concentrations at 0, 4, 6, and 8 min after the start of the glucose injection were performed in connection with a health examination survey of middle-aged men. The possible predictive value for later diabetes mellitus of early serum insulin response after intravenous glucose administration was evaluated by studying subjects with a familial history of diabetes mellitus and patients with different degrees of glucose intolerance. The following conclusions were drawn: The early appearance of glucose-stimulated serum insulin should be studied during the first 6 min after start of the glucose injection. The advantage of making calculations for early insulin secretion by including approximate considerations of the fractional removal rate of serum insulin is not apparent. Serum insulin values in patients with decreased glucose tolerance and subjects with a familial history of diabetes mellitus were best characterized by an insulin concentration index (glucose-stimulated early serum insulin concentration divided by basal serum insulin concentration). This index was significantly lower in these groups than in healthy controls.