Acute hemodynamic effects of estrogen administration in postmenopausal women

The hemodynamic effects of estrogens in replacement doses have not been fully clarified; therefore, we studied the acute hemodynamic changes after 0.625 and 1.25 mg of conjugated estrogens, administered intravenously, using a thermodilution catheter, in postmenopausal women without structural heart disease. Pulmonary and systemic pressures and resistances and stroke volume did not change compared with baseline, but heart rate and cardiac output decreased significantly, which may be associated with estrogen's previously described calcium-blocking effect or with a more recently contemplated beta-blocking action.     

Effect of intracoronary estrogen on coronary collateral blood flow velocity

The effect of estrogen on collateral circulation has not been previously investigated. We assessed the acute effect of estradiol on collateral blood flow velocity with the Flowire during percutaneous transluminal coronary angioplasty and found that intracoronary estradiol decreased collateral blood flow velocity compared with controls.     

T2 relaxation time study of iron overload in b-thalassemia

Myocardial iron deposition occurs as a result of blood transfusion therapy in b-thalassemia major patients. Since this deposition causes various cardiac complications, it is of interest to assess the iron content of the myocardium in relation to the clinical picture of the patients. Two different MRI indices were used to achieve this purpose: the T2 relaxation time and the heart/skeletal muscle signal intensity ratio. ECG gated spin echo images were obtained from 54 adult thalassemic patients, with a mean age of 26 (18–44) years, at TE = 22 ms and 60 ms, using a 1.5 T system. Patients were divided into 2 groups (A and B), according to their serum ferritin levels (> or < 2000 ng ml^-1). Results were compared with nine controls, with a mean age of 25 (18–43) years. Heart T2 relaxation time in controls (44.3 ± 3.5 ms) was higher than in group A (29.9 ± 5.7 ms,P< 0.001) and group B (33.4 ± 6.8 ms,P < 0.01). T2 was measurable in 66% of group A and 83% of group B patients. The heart/muscle signal intensity ratio in group A (0.45 ± 0.27) was lower than in group B (0.82 ± 0.33,P < 0.001) and the controls (1.15 ± 0.20,P < 0.001). The heart/muscle signal intensity ratio was measurable in 94% of the patients and demonstrated an inverse relationship with the serum ferritin levels(r = - 0.52, P<0.01). This study indicates that the heart/muscle ratio is a sensitive index of iron overload and it can be measured in the majority of patients, irrespective of tissue iron concentration, thereby offering an advantage over the use of T2 relaxation time. © 1998 Elsevier Science B.V. All rights reserved.     

Central serotonergic responsiveness in neurocardiogenic syncope: a clomipramine test challenge

BACKGROUND: Central serotonergic mechanisms appear to participate in the pathogenesis of recurrent neurally mediated syncope. The aim of the study was to investigate the responsiveness of the central serotonergic system by measuring the prolactin and cortisol responses to intravenous administration of the serotonin reuptake inhibitor clomipramine. METHODS AND RESULTS: Twenty subjects free of any medical treatment were tested. Twelve had a history of recurrent syncopal attacks and positive tilt test (patient group, mean age 47+/-18 years, 8 men); 8 subjects without syncope and a negative tilt test result served as control subjects (mean age 49+/-10 years, 5 men). Twenty-five milligrams of clomipramine was administered intravenously within 15 minutes, and blood samples were taken at 0, 15, 30, 45, and 60 minutes. Two days later, a tilt test was performed at 60 degrees for 30 minutes and blood samples were taken at 0, 10, 20, and 30 minutes. During the clomipramine challenge, plasma prolactin levels increased in both groups. The levels at 30 minutes were higher in the patient group compared with the control group (17.3+/-7.2 vs 9.3+/-7.6 ng/mL, P=0.05). Similar results were observed for cortisol at 30 minutes (172+/-15 vs 118+/-21 ng/mL P=0. 04) and at 45 minutes (189+/-20 vs 116+/-23 ng/mL, P=0.03). The tilt test was positive in 8 (67%) out of 12 of the patient group and negative in all control subjects. In the samples taken during the tilt test, significant increases in prolactin and cortisol were observed only in the subjects with positive tilt test results. CONCLUSIONS: Patients with a history of neurocardiogenic syncope show a higher responsiveness of the central serotonergic system to clomipramine challenge. The results support the view that central serotonergic mechanisms are involved in the pathophysiology of the syndrome.     

The PKC activator PMA preconditions rabbit heart in the presence of adenosine receptor blockade: is 5'-nucleotidase important?

While there is good evidence that both protein kinase C (PKC) and adenosine are involved in ischemic preconditioning, their sequence in the intracellular signaling cascade is in dispute. One hypothesis proposes that PKC activation causes release of adenosine which then protects the heart, while the other proposes that adenosine stimulates PKC which in turn causes protection. Accordingly, we studied the effects of specified sequences of pharmacologic triggers and blockers on the infarct-sparing effect of a preconditioning protocol. The combination of the adenosine receptor agonist R(-)N6-(2-phenylisopropyl) adenosine (PIA) and the PKC blocker chelerythrine would be protective only if the first hypothesis were correct. On the other hand, the combination of the adenosine receptor blocker 8-(p-sulfophenyl) theophylline (SPT) and a PKC activator would be protective only if the second hypothesis were correct. Isolated, Krebs-perfused rabbit hearts experienced 30 min of regional ischemia and 2 h of reperfusion. Infarct size was quantitated by triphenyltetrazolium chloride staining. In untreated control hearts, 30.0 +/- 2.7% of the risk zone infarcted. Fifty nmol/l PIA for 20 min starting 10 min prior to ischemia resulted in only 8.4 +/- 1.9% infarction (P<0.01), while the combination of PIA and 5 micromol/l chelerythrine resulted in large infarcts of 27.8 +/- 3.2%. This attenuation of the protective effect continued to be observed even when the PIA infusion was continued to the end of the reperfusion period. Conversely, 0.2 nmol of the PKC activator phorbol 12-myristate 13-acetate (PMA) infused during the 10-min interval prior to ischemia protected the hearts (6.5 +/- 1.3% infarction, P<0.01 v control). And protection persisted when PMA-treated hearts were also exposed to 100 microM SPT for 35 min starting 5 min prior to ischemia (9.5 +/- 1.9% infarction, P<0.01 v control). When PKC activation by the PKC-coupled agonist phenylephrine was continued to the end of ischemia and adenosine blockade was extended throughout the reperfusion period by prolonged infusion of SPT, protection was unaffected. The administration of either SPT or chelerythrine alone did not confer any protection (32.5 +/- 3.3 and 34.0 +/- 3.2% infarction, respectively). Thus, because the combination of PKC activation and adenosine receptor blockade was protective while that of adenosine receptor agonist and PKC blockade was not, adenosine receptors must be upstream of PKC in preconditioning.     

Randomized comparison of etoposide pharmacokinetics after oral etoposide phosphate and oral etoposide

Etoposide phosphate is a water-soluble prodrug of etoposide. The plasma pharmacokinetics of etoposide following oral administration of etoposide phosphate or oral etoposide were compared. Seventeen patients with solid tumours were enrolled to receive oral etoposide phosphate 125 mg m(-2) on days 1-5 every 3 weeks, with escalation to 175 mg m(-2) from course 3 when possible. Patients were randomized to receive oral etoposide phosphate or oral etoposide on day 1 of course 1 and the alternative compound on day 1 of course 2. Fifteen patients received two or more courses and were evaluable for pharmacokinetic comparisons. The median AUC(inf) (area under the concentration vs time curve from zero to infinity) of etoposide was 77.7 mg l(-1) h after etoposide phosphate (95% CI 61.3-100.5) and 62.0 mg l(-1) h after oral etoposide (95% CI 52.2-76.9). The difference in favour of etoposide phosphate was borderline significant: median 9.9 mg l(-1) h (95% CI 0.1-32.8 mg l(-1) h; P = 0.05). However, the inter-patient variability of etoposide AUC(inf) was not improved (coefficients of variation 42.3% and 48.4%). Etoposide phosphate was undetectable in plasma after oral administration. Toxicities of oral etoposide phosphate were not different from those known for etoposide. In conclusion, oral etoposide phosphate does not offer a clinically relevant benefit over oral etoposide.     

Coronary flow reserve in the contralateral artery increases after successful coronary angioplasty in patients with spontaneously visible collateral vessels

Due to the large variability in the reported contribution of bladder dysfunction to postprostatectomy incontinence and the impact this dysfunction may have on the outcome of selected treatment, we retrospectively reviewed the videourodynamic findings of bladder and sphincteric function in patients with postprostatectomy incontinence. The contributions of bladder and sphincteric causes of incontinence are determined. Ninety-two patients had multichannel videourdynamic testing performed as part of a comprehensive evaluation for incontinence at least 1 year after prostatectomy. Using a 6-French double-lumen catheter in the bladder and a 10-French catheter in the rectum, all pressures were recorded continuously while in the upright position. Valsalva leak point pressures (VLPP) were measured in the absence of a bladder contraction at a 150-ml volume and at 50-ml increments thereafter until maximum functional capacity was reached. Bladder compliance and bladder capacity were determined and the presence of detrusor instability (DI) was documented. Sixty-five patients (71%) presented after radical prostatectomy (RP) and 27 patients (29%) after transurethral resection of the prostate (TURP). The predominant urodynamic finding was sphincteric incompetence as VLPP were obtained in 85 patients (92%) and ranged from 12 to 120 cm water. DI was a common finding, occurring in 34 patients (37%), and classified as follows: a) phasic instability in 22/34, b) tonic instability in 3/34, and c) mixed phasic and tonic instability in 9/34. However, we found DI to be the sole cause of incontinence in only 3/92 patients (3.3%). There was no statistically significant difference in the incidence of sphincteric incompetence after RP or TURP; however, TURP patients had a higher incidence of DI, which was statistically significant (P=0.019). There was no correlation of incontinence severity and VLPP when comparing preoperative pad usage to VLPP < or =70 or > or =71 cm water. Although bladder dysfunction may be contributing problem in patients with postprostatectomy incontinence, it is rarely the only mechanism for this disorder. VLPP does not correlate with incontinence severity. Although sphincteric incompetence is the most common mechanism contributing to incontinence after prostatectomy, bladder dysfunction may coexist or be an isolated cause of postprostatectomy incontinence. Therefore, urodynamic studies are important to illustrate the exact cause(s) of incontinence in each individual patient after prostatectomy.     

Coronary collateral blood-flow velocity improves with repeated coronary occlusions during angioplasty in patients with coronary artery disease and systemic hypertension

The heterogeneity of schizophrenia has led to a multitude of diagnostic criteria systems. Thus, the best strategy for schizophrenia research might be the use of several diagnostic systems simultaneously. This polydiagnostic approach can be associated with isolating subtypes of symptoms or patients. In this way, the authors present several approaches such as, first, dimensional approaches, second, cluster analyses, and third the selection of a very homogeneous subtype with standardized criteria. One homogeneous subtype can be represented by deficit schizophrenia according to Carpenter as defined by the Schedule of Deficit Syndrome.     

The effect of hormone replacement therapy alone and in combination with simvastatin on plasma lipids of hypercholesterolemic postmenopausal women with coronary artery disease

Follicular growth, lifespan of the corpus luteum, and antioxidant status of lactating Holsteins that experienced heat stress were monitored. Eleven multiparous cows, 60 to 110 d in milk, were maintained from 0800 to 1800 h daily in environmental chambers from d 11 to 21 of the estrous cycle. Cows were randomly assigned to a heat stress (mean dry bulb temperature peaked at 38.3 degrees C) or control treatment (mean dry bulb temperatures varied from 20.8 to 25.6 degrees C). Rectal temperature and respiration rates of heat-stressed cows were higher at 1600 h than were those of control cows. The length of the estrous cycle and the interval from estrus until luteolysis were not different between treatments. Two of 6 control cows and 1 of 5 heat-stressed cows had extended cycles (> 24 d). Heat-stressed cows had more class 1 (2 to 5 mm) follicles from d 11 to 15 of the estrous cycle. Numbers of class 2 (6 to 9 mm) and class 3 (> or = 9 mm) follicles were similar between treatments. Plasma progesterone concentrations were higher for heat-stressed cows until d 19 of the estrous cycle. Treatment did not affect concentrations of alpha-tocopherol, beta-carotene, retinol, retinyl palmitate, or total protein in plasma or concentrations of malondialdehyde in muscle. In conclusion, heat stress did not extend luteal function or the length of the estrous cycle of lactating Holstein cows but did affect follicular growth and progesterone concentrations in plasma. Heat stress did not appear to increase lipid peroxidation or decrease lipid-soluble antioxidant concentrations in blood.     

Decreased post-myocardial infarction heart rate variability and cardiac denervation assessed by metaiodobenzylguanidine scintigraphy

Decreased heart rate variability, assessed 2 weeks after uncomplicated acute myocardial infarction, is related to the extent of 1-123-metaiodobenzylguanidine-derived efferent sympathetic cardiac denervation. This postinfarction cardiac denervation could be the substrate of reduced postinfarction heart rate variability.