Acute and delayed hormonal changes in mitral stenosis treated by balloon valvulotomy

The role of left atrial and aortic pressures on the secretion of the main hormones controlling blood volume is still subject to debate in humans. Because of increased mean left atrial pressure and decreased mean aortic pressure produced by balloon inflation in patients with mitral stenosis treated with balloon valvulotomy, the hormonal changes occurring acutely (group II of patients) were measured. The same studies (group I patients) were also performed 48 hours after this treatment, a period at which left atrial pressure permanently diminished. Inflation of the balloon resulted in a decrease in plasma renin activity and increases in plasma atrial natriuretic factor (ANF) and plasma arginine vasopressin (AVP). Forty-eight hours after balloon valvulotomy, which had produced a decrease in left atrial pressure, plasma ANF was lower (58.9 +/- 7.9 vs 95.3 +/- 11.9 pg/ml; p < 0.001), and plasma renin activity (2,575 +/- 533 vs 960 +/- 113 pg/ml/hour; p < 0.01), plasma angiotensin II (25.0 +/- 4.1 vs 9.3 +/- 1.3 pg/ml; p < 0.001) and plasma aldosterone (181.7 +/- 36.7 vs 139.9 +/- 19.8 pg/ml; p < 0.05) were higher than their respective control levels 24 hours before treatment of the stenosis. In contrast, plasma AVP (3.7 +/- 0.25 vs 4.4 +/- 0.31 pg/ml; p = 0.001) diminished moderately along with plasma osmolality (282.4 +/- 0.1 vs 286.2 +/- 0.6 mOsm/kg; p < 0.001). Urinary sodium excretion was also examined before and after balloon valvulotomy.(ABSTRACT TRUNCATED AT 250 WORDS)     

MR guidance of laser disc decompression: preliminary in vivo experience

BACKGROUND: The mechanism of atrial natriuretic peptide (ANP) release has been difficult to demonstrate in patient studies because of inaccuracies in measuring atrial volumes using conventional techniques. METHODS: Magnetic resonance imaging was performed in 28 clinically stable patients (New York Heart Association class 3) with chronic heart failure to determine right atrial (RA), left atrial (LA), and ventricular volumes. In addition, right heart catheterization was serially performed and plasma ANP levels (in picograms per milliliter) were drawn from the right atrium. RESULTS: Five patients had to be excluded from data analysis for technical reasons. The remaining 23 patients had the following hemodynamic measurements (mean +/- SD): RA mean pressure 7+/-5 mm Hg, pulmonary artery mean pressure 28+/-10, pulmonary capillary wedge pressure 21+/-8 mm Hg, and cardiac index 2.9+/-1.4 (L/min/m2), respectively. Plasma ANP levels were significantly elevated at 162+/-117 (normal range 20 to 65 pg/ml, p < 0.05), as were LA and RA volumes compared with healthy controls (RA volume 128+/-64 ml vs 82+/-25 ml, p < 0.05; LA volume 157+/-54 ml vs 71+/-24 ml, p < 0.01, respectively). ANP showed a stronger relation with atrial volumes (RA volume, r = 0.91, p = 0.0001; LA volume, r = 0.80, p = 0.001) than with atrial pressures (RA mean pressure, r = 0.45, p = 0.03; pulmonary capillary wedge pressure, r = 0.67, p = 0.001). A subgroup analysis of patients with increased RA or LA volumes (>1 SD of mean of controls) revealed a stronger relation between ANP and RA volumes than between ANP and LA volumes. CONCLUSIONS: These data suggest that increased right heart volume with subsequent increased atrial stretch is the major determinant for ANP release in patients with stable CHF.     

Molecular analysis of the histone gene cluster of Psammechinus miliaris: III. Polarity and asymmetry of the histone-coding sequences

The Ca2+ antagonistic coronary vasodilator, Nifedipine, was sublingually administered by a dose of 30 mg to 19 patients with hypertension. Blood pressure of patients with with essential hypertension (n=14) decreased from 177 +/- 24 to 123 +/- 13 mmHg systolic and from 108 +/- 12 to 80 +/- 11 mmHg diastolic (mean +/- SD) (p less than 0.01). Plasma renin activity (PRA) increased significantly from 0.73 +/- 0.62 to 1.50 +/- 1.02 ng/ml/h (p less than 0.05). The same tendency was observed in malignant and renovascular hypertension. In primary aldosteronism (n = 2), blood pressure decreased but PRA did not increase. Hypotensive action and increased plasma renin activity by Ca2+ antagonist, Nifedipine, were clearly demonstrated in patients with hypertension.     

C-reactive protein (CRP) as a marker of of hemodialysis biocompatibility]

Haemodialysis leads to monocytes activation and secretion of cytokines, which stimulates hepatic production of CRP. To assess the biocompatibility of haemodialysis the CRP serum levels were measured. CRP serum levels during haemodialysis with the use of cuprophane membranes increased from 4743.3 +/- 3251.6 ng/ml to 5231.8 +/- 3458.4 ng/ml just after haemodialysis and 5865.4 +/- 3684.8 ng/ml 22 hours after haemodialysis (p < 0.001). During haemodialysis using polysulfone membranes CRP from the initial value of 4819.4 +/- 4328.2 ng/ml decreased to 3316.9 +/- 3882.7 ng/ml just after haemodialysis (p < 0.01) and increased to 5086.9 +/- 4193.0 ng/ml 22 hours after haemodialysis (p < 0.05). Re-counted CRP values, according to changes in total blood protein, increased significantly (p < 0.02) 22 hours after haemodialysis with the use of cuprophane membranes. During haemodialysis using polysulfone membranes above mentioned levels were significantly decreased just after haemodialysis (p < 0.001). The cuprophane membranes surface area and reutilization of dialyzers did not affect the changes of CRP serum levels. No correlation was observed between CRP level changes and dialysis neutropenia and complement activation. Our results indicate, that CRP serum level measurement may be feasible to assess the biocompatibility of dialysis membranes.     

Transesophageal echocardiographic predictors for maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation

The aim of this study was to assess the value of transesophageal echocardiography (TEE) in patients with atrial fibrillation in predicting restoration and maintenance of sinus rhythm after electrical cardioversion. TEE was performed in 62 patients with atrial fibrillation before their first elective cardioversion. Clinical variables evaluated were: age, gender, duration, and etiology of atrial fibrillation. TEE variables included: left atrial (LA) length, width, and size, LA annulus size, as well as presence of LA spontaneous contrast, thrombus and mitral regurgitation, LA appendage size and flow, and left ventricular function. Based on initial outcome of cardioversion, patients were grouped into patients who remained in atrial fibrillation and in whom sinus rhythm was restored. The latter group of patients was followed for 1 year, and grouped into patients who reverted to atrial fibrillation and in whom sinus rhythm was maintained. Successful cardioversion was achieved in 50 of 62 patients (81%). None of the clinical or TEE variables were related to initial outcome. At 1-year follow-up, 29 of 50 patients (58%) who underwent successful cardioversion continued to have sinus rhythm. The following variables were related to maintenance of sinus rhythm: duration of atrial fibrillation (6.7 +/- 7.3 vs 2.0 +/- 2.4 months; p < 0.005); LA length (6.2 +/- 0.7 vs. 5.5 +/- 1.0 cm; p < 0.008); width (5.1 +/- 0.5 vs. 4.5 +/- 0.7 cm; p < 0.002); size (26.4 +/- 5.0 vs 19.8 +/- 6.5 cm2; p < 0.0005); annulus size (4.0 +/- 0.2 vs 3.7 +/- 0.3 cm; p < 0.0005); presence of LA spontaneous contrast (13 [62%] vs 4 [14%]; p < 0.002), and LA appendage flow (19 +/- 8 vs 36 +/- 15 cm/s; p < 0.0005). In multivariate logistic regression analysis, LA annulus size, but especially LA appendage flow, were significantly associated with maintenance of sinus rhythm. Thus, in TEE-guided electrical cardioversion of atrial fibrillation, variables often used to assess thromboembolic risk may also be used to predict 1-year outcome of cardioversion.     

Synchrony in telomere length of the human fetus

We measured serum tumour necrosis factor-alpha (TNF-alpha) as well as interleukin-1betta (IL-1beta) and GH concentrations in 15 children with isolated growth hormone deficiency (GHD), age range 5.1-13.9 years, before and 4 and 24h after the first GH injection (0.1 IU/kg s.c.). No differences were found in basal concentrations of serum TNF-alpha and IL-1beta between GHD children (10.01 +/- 1.55 pg/ml and 2.14 +/- .16 ng/ml respectively) and sex- and age-matched controls (11.57 +/- 2.16 pg/ml and 3.78 +/- 1.46 ng/ml respectively). In GHD children, serum TNF-alpha and IL-1beta values had significantly increased (P < 0.002) 4h (26.75 +/- 5.57 pg/ml and 2.99 +/- 0.21 ng/ml respectively) and decreased again 24 h after GH administration. Likewise, serum GH levels had significantly increased 4 h (from 1.29 +/- 0.69 to 48.71 +/- 13.35 ng/ml, P < 0.001) and decreased to basal values 24h after GH administration. A significant correlation was found between basal serum concentrations of GH and those of both TNF-alpha (P < 0.01) and IL-1beta (P < 0.05). However, no correlation was found between serum GH concentration and either TNF-alpha or IL-1beta levels 4 and 24h after GH administration. Our data suggest that GH plays a role in modulating TNF-alpha and IL-1beta release in humans.     

Comparison of amlodipine and quinapril on ambulatory blood pressure and platelet function in hypertension

The effect of calcium channel blocker (CCB), amlodipine (5-10 mg/day) and angiotensin-converting enzyme (ACE) inhibitor, quinapril (10-40 mg/day) on ambulatory blood pressure (ABP), rheological and platelet function in hypertension were compared in this randomised double-blind placebo-controlled cross-over study. This study was preceded by 4 weeks placebo run-in period and the total duration of the study was 28 weeks. Casual and 24 h ABP, plasma renin activity (PRA) and plasma aldosterone (PA) concentration as well as metabolic and platelet function were determined before and at the end of each drug therapy. A total of 27 patients completed this study. Casual BP was significantly reduced after amlodipine or quinapril treatment, but there was no change in heart rate. Regarding the 24 h ABP, amlodipine produced a fall from 145 +/- 8/94 +/- 7 to 130 +/- 13/85 +/- 10 mm Hg (P < 0.001 for both SBP and DBP). Quinapril also caused a reduction from 144 +/- 10/94 +/- 7 to 134 +/- 12/88 +/- 8 mm Hg (P < 0.001 for both SBP and DBP). Neither amlodipine nor quinapril produce any significant change in heart rate. The level of 6-keto-prostaglandin Fl alpha (6-Keto-PGFl alpha) was increased from 36.8 +/- 4.4 to 45.1 +/- 2.5 pg/ml (P < 0.05) and no significant change of thromboxane B2(TXB2) was noted after amlodipine treatment. PRA was increased from 1.24 +/- 0.31 to 1.62 +/- 0.41 ng/ml/h (P < 0.05) after quinapril treatment. Other biochemical parameters were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Rebound increase of PAI-1 following local intra-arterial rt-PA infusion, a possible cause of reocclusion

We obtained normative data for plasma renin activity (PRA) and plasma aldosterone concentration from a biracial sample of 195 healthy, normotensive children and adolescents aged 10 to 18 years. The sample included 119 boys and 76 girls, of whom 103 were black and 92 were white. The mean PRA value (+/- SD) was 2.52 +/- 1.95 ng/ml per hour, with minimal and maximal values of 0.1 and 13.50 ng/ml per hour. The mean plasma aldosterone concentration was 12.56 +/- 8.59 ng/ml, with minimal and maximal values of 1.6 and 50.1 ng/ml. We also examined the effects of subject characteristics and electrolyte intake. The slope relating sodium excretion to PRA was negative and highly significant (slope = -0.01; p < 0.003). The slope relating PRA to plasma aldosterone concentration was positive and highly significant (slope = 1.59; p < 0.0001). We did not observe differences in either variable as a function of age, sex, race, or family history of hypertension. These results suggest that differences based on race and family history of hypertension observed in adults are not present in youth.     

Clinical characteristics of schizophrenia associated with velo-cardio-facial syndrome

The aim of this study was to investigate whether melatonin might modulate the daily prolactin secretion in the ewe during a period of ovarian activity and, if so, whether this modulatory action of melatonin was related to the presence of estradiol in the organism. Ewes in the late follicular and luteal phase, as well as overiectomized ewes without (OVX) and after 7 days of estradiol injections (OVX+E2) were examined. Melatonin was infused into the third brain ventricle (100 microgram/100 microliter/h) from 14.00 to 18.00 h. The concentration of prolactin increased significantly during the infusion of melatonin in late follicular-phase ewes, but not in luteal-phase ewes, as compared to the concentration before the infusion: range from 204.0 +/- 31.7 to 272.2 +/- 50.1 ng/ml vs. range from 68.2 +/- 31.8 to 94.7 +/- 33.1 ng/ml (mean +/- SEM, n = 4, p < 0.01) and to the concentration noted during control infusions: range from 130.0 +/- 58.0 to 179.3 +/- 55.6 ng/ml (mean +/- SEM, n = 4, p < 0.05). In ovariectomized ewes, the concentration of prolactin during infusion of melatonin increased significantly, unrelated to the presence of estradiol, as compared to the concentration before infusion: range from 136.7 +/- 20.3 to 260.0 +/- 11.6 ng/ml vs. range from 41.6 +/- 2.6 to 152.3 +/- 14.6 ng/ml in OVX ewes (mean +/- SEM, n = 4, p < 0.01) and range from 161.5 +/- 66.5 to 250.2 +/- 24.3 ng/ml vs. range from 61.2 +/- 1.7 to 159.2 +/- 43.3 ng/ml in OVX+E2 ewes (mean +/- SEM, n = 4, p < 0.01). Concentrations during infusion of melatonin in OVX and OVX+E2 ewes were also significantly higher than during the control infusions: range from 7.2 +/- 1.7 to 22.2 +/- 4.1 ng/ml (mean +/- SEM, n = 4, p < 0.001). These results indicate that melatonin may affect the daily secretion of prolactin in ewes during the breeding season, and suggest that the variable response of prolactin to the melatonin signal in intact and ovariectomized ewes relates to the interaction between both ovarian steroids - estradiol and progesterone - and the prolactin-releasing factor.     

Atrial natriuretic peptide-induced release of cyclic guanosine monophosphate by coronary bypass grafts

BACKGROUND: Superior long-term patency rates of the internal mammary artery (IMA) versus saphenous vein (SV) after coronary artery bypass grafting are well documented. Higher production rates of vasodilating and platelet-inhibiting mediators (prostacyclin and nitric oxide) by the IMA seem to have a major impact on its long-term durability and resistance to coronary artery graft disease. For the right gastroepiploic artery (RGEA) marked release of protective mediators is reported as well. The vasodilating effect of cyclic guanosine monophosphate (cGMP) released after stimulation by atrial natriuretic peptide might serve as another graft protective system. The aim of the present study was to determine cGMP release by IMA, RGEA, and SV after atrial natriuretic peptide challenge. METHODS: Samples of human IMA (n = 19), RGEA (n = 7), and SV (n = 18) discarded during coronary artery bypass grafting were stimulated with 10(-6) mol/L atrial natriuretic peptide after a resting phase in nutrient medium. Release of cGMP was determined by 125-iodide radioimmunoassay. RESULTS: Basal cGMP production rates of the IMA (759.9 +/- 277.0 fmol/cm2) and RGEA (739.9 +/- 186.0 fmol/cm2) were higher than production rates of SV (281.2 +/- 64.0 fmol/cm2). Application of atrial natriuretic peptide led to a statistically significant increase of cGMP release in IMA grafts (1,939.3 +/- 778.0 fmol/cm2), whereas RGEA (618.4 +/- 141.3 fmol/cm2) and SV (221.7 +/- 64.5 fmol/cm2) remained at basal levels (p < 0.05). CONCLUSIONS: From these data we conclude that the IMA in comparison with the RGEA and SV produces more extracellular cGMP when stimulated by atrial natriuretic peptide. This effect might support the cGMP-mediated protective properties of nitric oxide and could underline the extraordinary suitability of the IMA as a bypass conduit.     

Plasma levels of atrial natriuretic peptide and brain natriuretic peptide following intravenous saline infusion in oedematous chronic obstructive pulmonary disease and non-oedematous chronic obstructive pulmonary disease

Some patients with chronic obstructive pulmonary disease (COPD) develop oedematous COPD (oCOPD) with peripheral oedema and have a poor prognosis. The cause of the fluid retention is poorly understood but could be due to defective release of a natriuretic factor. We investigated this hypothesis by measuring levels of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) before and after a 0.1 ml/kg/min 2.7% saline infusion in 6 patients with hypoxemic COPD but no history of oedema and 7 COPD patients with oCOPD. Vasopressin, aldosterone, plasma and urinary urea and electrolytes and osmolality were measured. Arterial blood gases and spirometry were also recorded. The two groups were similar in terms of age, weight, PaO2, PaCO2 and FVC. FEV1 was significantly lower in the oCOPD group. The oCOPD group excreted less urine (202 +/- 23 vs. 364 +/- 48 ml; p < 0.05) and less sodium (32 +/- 3 vs. 68 +/- 9 mmol/l; p < 0.01) as a percentage of the saline load given (18 +/- 2 vs. 30 +/- 4%; p < 0.05). Pre-infusion BNP and ANP levels were similar in both groups. BNP and ANP had an exaggerated increase in the oCOPD group on saline loading. In the oCOPD group, ANP levels were significantly greater 1 h after the saline load compared to the pre-infusion values (30 +/- 7 vs. 11 +/- 2; p < 0.05). BNP did not reach significantly greater levels than baseline values until 3 h after the infusion had ended (45 +/- 6 vs. 27 +/- 2; p < 0.05). At 1 h after the saline load, BNP and ANP levels were significantly greater in the oCOPD group (BNP 32 +/- 2 vs. 24 +/- 1; p < 0.01 and ANP 30 +/- 7 vs. 7 +/- 2; p < 0.05) when compared to COPD controls. BNP levels remained significantly different from the COPD control group 3 h after the infusion ended (45 +/- 6 vs. 26 +/- 2; p < 0.05). Although aldosterone levels were greater in the oCOPD group before the saline infusion, the hormone level was suppressed appropriately by the infusion. In conclusion, the cause of oedema in oCOPD and the inability to excrete a saline load is not due to a failure of release of BNP or ANP.     

A YAC-based transcript map of human chromosome 9q22.1-q22.3 encompassing the loci for hereditary sensory neuropathy type I and multiple self-healing squamous epithelioma

The release of lipoteichoic acid (LTA) and teichoic acid (TA) from a Streptococcus pneumoniae type 3 strain during exposure to ceftriaxone, meropenem, rifampin, rifabutin, quinupristin-dalfopristin, and trovafloxacin in tryptic soy broth was monitored by a newly developed enzyme-linked immunosorbent assay. At a concentration of 10 microg/ml, a rapid and intense release of LTA and TA occurred during exposure to ceftriaxone (3,248+/-1,688 ng/ml at 3 h and 3,827+/-2,133 ng/ml at 12 h) and meropenem (2,464+/-1,081 ng/ml at 3 h and 2,900+/-1,364 ng/ml at 12 h). Three hours after exposure to rifampin, rifabutin, quinupristin-dalfopristin, and trovafloxacin, mean LTA and TA concentrations of less than 460 ng/ml were observed (for each group, P < 0.01 versus the concentrations after exposure to ceftriaxone). After 12 h of treatment, the LTA and TA concentrations were 463+/-126 ng/ml after exposure to rifampin, 669+/-303 ng/ml after exposure to rifabutin, and 1,236+/-772 ng/ml after exposure to quinupristin-dalfopristin (for each group, P < 0.05 versus the concentrations after exposure to ceftriaxone) and 1,745+/-1,185 ng/ml after exposure to trovafloxacin (P = 0.12 versus the concentration after exposure to ceftriaxone). At 10 microg/ml, bactericidal antibacterial agents that do not primarily affect cell wall synthesis reduced the amount of LTA and TA released during their cidal action against S. pneumoniae in comparison with the amount released after exposure to beta-lactams. Larger quantities of LTA and TA were released after treatment with low concentrations (1x the MIC and 1x the minimum bactericidal concentration) than after no treatment for all antibacterial agents except the rifamycins. This does not support the concept of using a low first antibiotic dose to prevent the release of proinflammatory cell wall components.     

Minor physical anomalies in schizophrenia and mood disorders

The purpose of the present study was to examine the effect of a two day and a five day administration of 22-oxa-calcitriol (OCT) on calcium metabolism in rats with advanced chronic renal failure and severe secondary hyperparathyroidism. A first series of 27 uremic rats received either placebo, OCT or calcitriol (0.3 microgram i.p./rat) 48 and 24 hours before sacrifice. A second series of 18 uremic rats received either placebo, OCT (0.3 microgram i.p./rat) or calcitriol (0.05 microgram i.p./rat) for five days. We found that after 48 hours (series 1) both calcitriol and OCT increased blood ionized calcium (Ca2+) as compared to vehicle (1.23 +/- 0.04 and 1.10 +/- 0.02 mM, P < 0.01 and P < 0.05, respectively vs. control, 1.02 +/- 0.03 mM). Duodenal Ca transport (S/M) using the everted gut sac technique was not stimulated by OCT, even though it increased from 2.8 +/- 0.4 to 7.0 +/- 0.6 (P < 0.01) with calcitriol. In contrast, duodenal calbindin-D9k mRNA expression and protein content increased to a similar extent with OCT and calcitriol. Calcitriol was more potent in reducing plasma iPTH1-34 levels than OCT: 344 +/- 75 pg/ml (calcitriol) versus 632 +/- 46 pg/ml (OCT) compared with 897 +/- 74 pg/ml (control), P < 0.01. In the second series of rats, the injection of OCT (0.3 microgram i.p./rat) over five days was less effective than the lower dose of calcitriol (0.05 microgram i.p./rat) in reducing circulating iPTH: 110 +/- 26 (calcitriol) and 281 +/- 64 (OCT) versus 624 +/- 135 pg/ml (control), P < 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of the effects of potential parenteral vehicles for poorly water soluble anticancer drugs (organic cosolvents and cyclodextrin solutions) on cultured endothelial cells (HUV-EC)

Left atrial (LA) adaptation during the development of left ventricular (LV) dysfunction is not fully understood. We performed echocardiographic assessment of LA volumes simultaneously with recordings of pulmonary wedge pressures in 60 patients. Twenty patients had no structural or functional LV abnormalities, 20 had a recent myocardial infarction with LV dysfunction, and 20 suffered from congestive heart failure (CHF). Pressure-volume loops were obtained at baseline and during increases in LA pressure produced by normal saline infusion. LA afterload was estimated by the effective LV elastance (E(LV)). Atrioventricular coupling was calculated by the E(LV)/E(es) ratio (where E(es) is the end-systolic elastance). E(es) increased in patients with myocardial infarction (0.80 +/- 0.09 mm Hg/ml, p <0.001), whereas it decreased in patients with CHF (0.22 +/- 0.05 mm Hg/ml, p <0.001) compared with controls (0.61 +/- 0.07 mm Hg/ml). Similarly, stroke workload increased in patients with myocardial infarction (60.7 +/- 7.3 mm Hg x ml, p <0.001), whereas it decreased in patients with CHF (25.4 +/- 2.2 mm Hg x ml, p <0.001) compared with controls (44.8 +/- 5.5 mm Hg x ml). In all patients LA stiffness (slope of the relation of the filling portion of the pressure-volume loop) was increased compared with controls (controls: 0.13 +/- 0.04, patients with myocardial infarction: 0.22 +/- 0.05, and patients with CHF: 0.27 +/- 0.05 mm Hg/ml, p <0.001 for both comparisons). Moreover, the E(LV)/E(es) ratio increased gradually as LV function deteriorated (controls: 1.06 +/- 0.10, patients with myocardial infarction: 1.35 +/- 0.16, and patients with CHF: 6.90 +/- 0.84, p <0.001). Thus, early in heart failure, LA pump function is augmented but LA stiffness increases and work mismatch occurs. With further progression of LV dysfunction, LA pump function decreases as a result of increased afterload imposed on the LA myocardium.     

Depletion of intravascular pools of tissue factor pathway inhibitor (TFPI) during repeated or continuous intravenous infusion of heparin in man

Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of the extrinsic coagulation system. TFPI is increased several-fold in postheparin plasma and thereby thought to contribute significantly to the antithrombotic action of heparin. The present study was conducted to investigate how repeated (n = 8) and continuous (n = 6) administration of heparin affect plasma TFPI and the inhibition of tissue factor (TF)-induced coagulation ex vivo in humans. Free TFPI antigen (TFPI Ag) increased from 19.2 +/- 4.0 ng/ml to 204.7 +/- 31.7 ng/ml after intravenous injection of 5000 IU of unfractionated heparin. Five repeated injections of 5000 IU of heparin at 4 h intervals caused a progressive decrease (-45 +/- 8%, p < 0.0001 for time effect) in heparin-releasable TFPI and a progressive shortening of the clotting time as determined in a dilute prothrombin time assay (dPT) (-8.7 +/- 6.1 s, p < 0.0001). The basal concentration of TFPI Ag in plasma collected immediately before each heparin injection was decreased by 29 +/- 15% (p < 0.0001), whereas the dPT was decreased by 6.9 +/- 3.5 s (p < 0.0001). During a 24 h continuous infusion of heparin TFPI Ag decreased from 161.5 +/- 26.0 ng/ml to 35.6 +/- 4.7 ng/ml (-77.3 +/- 5.1%) (p < 0.0001). The contribution of TFPI to the inhibition of TF-induced coagulation during heparin infusion was estimated to decrease from 60 +/- 15% to 20 +/- 10% (p < 0.0001). The present data indicate partial depletion of intravascular pools of TFPI by repeated and continuous heparin administration and thereby attenuation of its contribution to the antithrombotic action of heparin.     

Precision and accuracy of bone landmarks in characterizing hand and wrist position

We have investigated the relationship between plasma endothelin (ET) concentrations and several clinical characteristics in 31 patients with acute myocardial infarction (MI). ET levels were also measured in 10 age-matched healthy subjects, 9 patients with unstable angina, and 20 patients with chronic heart disease. In patients with MI, although no significant relationship was observed between plasma ET concentrations and measured hemodynamic parameters, plasma levels were higher in patients with pulmonary congestion than in those without this complication (1.61 +/- 0.29 vs 1.21 +/- 0.33 fmol/ml; p < 0.01). No significant difference in plasma ET levels was found between cardiac and peripheral sampling sites (pulmonary artery; 1.07 +/- 0.28, right atrium; 1.02 +/- 0.28, peripheral artery; 1.12 +/- 0.23, peripheral vein; 1.14 +/- 0.38 fmol/ml: N.S.), or among patients with uncomplicated MI, unstable angina (1.00 +/- 0.32 fmol/ml), and healthy subjects (1.01 +/- 0.29 fmol/ml). Increased level were observed in patients with decompensated heart failure due to chronic heart disease, but were not found in patients without pulmonary congestion (1.62 +/- 0.60 vs 1.11 +/- fmol/ml; p < 0.01). These observations suggest that plasma ET concentrations are elevated in the presence of congestive heart failure or severe ventricular depression, but are not persistently increased by myocardial ischemia per se.     

Atypical strains of verocytotoxin-producing Escherichia coli O157 in beef cattle at slaughter in Veneto region, Italy

A population-based study was performed in order to study the interrelationships of the circulating components of the renin-angiotensin system during basal conditions and their relations to blood pressure (BP), age and gender. One hundred and four women and 95 men, 16-70 years old, evenly age distributed and randomly selected from the population of Link?ping, Sweden, participated. Venous blood was drawn at 08.00 hours and ambulatory BP recording was then performed. Serum angiotensin-converting enzyme (ACE) activity correlated with plasma angiotensin II (r = 0.20, P = 0.004), but when calculated separately according to gender, the correlation remained significant only in men (r = 0.33, P = 0.001). Plasma renin activity (PRA) correlated negatively with age (r = -0.30, P < 0.0001), but immunoreactive active renin (IRR) and angiotensin II did not. PRA and IRR correlated negatively with BP in women but correlations disappeared after age adjustment. The 23 women on oestrogen medication did not differ from the remaining 81 with respect to age (P = 0.5), IRR (P = 0.96) or angiotensin II (P = 0.4) levels, but PRA was higher (2.2 +/- 1.4 ng Ang l/ml/h and 1.5 +/- 0.9 ng Ang l/ml/h, respectively, P = 0.004). PRA (r = 0.38, P < 0.0001) and IRR (r = 0.49, P < 0.0001) correlated positively with the levels of angiotensin II. In conclusion the fact that PRA, but not IRR, declined with age and was higher among oestrogen-treated women, although angiotensin II was unaffected suggests IRR to be a more robust marker of angiotensin II levels than is PRA in a population-based setting. ACE correlates positively with angiotensin II in men.     

Bone mass improves in alcoholics after 2 years of abstinence

To evaluate the effect of abstinence on bone mass and bone mineral metabolism in chronic alcoholics, a 2 year longitudinal follow-up study was carried out in a group of 30 chronic alcoholic males who started a rehabilitation program. Lumbar and femoral bone mineral density (BMD) and serum levels of osteocalcin and 25-hydroxyvitamin D were measured at entry and after 1 and 2 years in all patients. Circulating cortisol and parathyroid hormone were measured in 14 and 6 patients, respectively, at entry and every year. Testosterone was measured in 18 patients at entry and after 1 year. At entry, lumbar BMD was significantly lower in alcoholics (1.06 +/- 0.03 g/cm2) than in age-matched healthy men (1.22 +/- 0.03 g/cm2; p < 0.001). Circulating osteocalcin and vitamin D levels were also significantly lower in alcoholics than in controls. Lumbar and femoral neck BMD increased in alcoholics after 2 years of abstinence (lumbar BMD, mean +/- SEM, 1.06 +/- 0.03 to 1.10 +/- 0.04 g/cm2, p < 0.05; femoral BMD, 0.82 +/- 0.02 to 0.84 +/- 0.02 g/cm2; p < 0.02). Moreover, lumbar BMD increased in alcoholics (2.9 +/- 1.4%) and decreased in controls (-1.1 +/- 0.2%; p < 0.02). Femoral BMD also increased in alcoholics (2.8 +/- 1.0%) but the expected mean decrease of -0.92% was found in healthy age-matched males. Baseline low osteocalcin levels (5.1 +/- 0.6 ng/ml) increased after 1 year (8.6 +/- 0.5 ng/ml, p < 0.001) and 2 years of abstinence (9.5 +/- 0.7 ng/ml, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Tumour necrosis factor alpha and interleukin 2 in normal and infected human seminal fluid

The presence of cytokines such as the tumour necrosis factor alpha (TNF alpha) and interleukin 2 (IL2) in human spermatozoa is still to be defined. The aim of this study was to measure the concentration of both soluble factors in seminal fluid. Data from normal semen samples (n = 24) confirmed the presence of IL2 (258 +/- 84 fmol/ml corresponding to 953 +/- 369 fmol/total volume of ejaculate) and TNF alpha (62.2 +/- 16.4 fmol/ml corresponding to 231.3 +/- 86 fmol/total volume of ejaculate). A significant positive correlation (r = 0.59; P < 0.01) was observed between the TNF alpha and the IL2 concentrations. The concentrations of these cytokines were not related to sperm parameters. In contrast, IL2 concentrations (196.9 +/- 60.4 fmol/ml; 686.2 +/- 236.7 fmol/total volume of ejaculate) evaluated in 16 seminal fluids with identified bacterial agents were lower than in the control group, whereas TNF alpha concentrations (68.6 +/- 12.3 fmol/ml; 241.3 +/- 78.9 fmol/total volume of ejaculate) were not significantly different from the controls. Further studies are needed to determine the potential role of these cytokines in the physiology of semen and their usefulness as indicators of reproductive pathology.     

Disparity between blood pressure and PRA inhibition after administration of a renin inhibitor to anesthetized dogs: methodological considerations

A dissociation between changes in blood pressure (BP) and plasma renin activity (PRA) has been noted after administration of renin inhibitors. In the present study, the renin inhibitor PD 132002 was given to salt-deplete, anesthetized dogs. PRA was measured at pH 6.0 by a conventional angiotensin I (ANG I) RIA method (PRA-C) and by an ANG I antibody-trapping RIA method (PRA-AT) performed at pH 7.4. PD 132002 at 0.01, 0.1, 1, and 10 mg/kg IV, reduced BP by 3 +/- 2, 9 +/- 2, 24 +/- 4, and 39 +/- 4 mm Hg, respectively, (baseline of 136 +/- 8 mm Hg, N = 5), when infused IV over 30 minutes with a 30 minute recovery between doses. The BP response at 10 mg/kg equaled that of saralasin (20 micrograms/kg/min IV). PRA-AT (baseline of 20 +/- 6 ng ANG l/ml/hr, N = 4) was inhibited by 0%, 28% +/- 12%, 75% +/- 10%, and 97% +/- 1% at 0.01, 0.1, 1, and 10 mg/kg, respectively. Plasma concentrations of immunoreactive ANG II were also reduced dose-dependently and paralleled changes in BP. In contrast, PRA-C (baseline of 13 +/- 4 ng ANG l/ml/hr, N = 4) was inhibited by 82% +/- 8% at 0.01 mg/kg and by > 98% at higher doses. After a single dose of PD 132002 at 10 mg/kg infused over 30 minutes, BP recovery paralleled changes in immunoreactive ANG II and PRA-AT, yet PRA-C inhibition showed no recovery over the same time course. Our data support the conclusion that BP relates better to PRA-AT than PRA-C. Thus the dissociation sometimes observed in studies with renin inhibitors between changes in BP and PRA may be attributed to the assay used to determine PRA.