Human heart: tagging with MR imaging--a method for noninvasive assessment of myocardial motion

Specified regions of the myocardium can be labeled in magnetic resonance (MR) imaging to serve as markers during contraction. The technique is based on locally perturbing the magnetization of the myocardium with selective radio-frequency (RF) saturation of multiple, thin tag planes during diastole followed by conventional, orthogonal-plane imaging during systole. The technique was implemented on a 0.38-T imager and tested on phantoms and volunteers. In humans, tags could be seen 60-450 msec after RF saturation, thus permitting sampling of the entire contractile phase of the cardiac cycle. Tagged regions appear as hypointense stripes, and their patterns of displacement reflect intervening cardiac motion. In addition to simple translation and rotation, complex motions such as cardiac twist can be demonstrated. The effects of RF pulse angle, relaxation times, and heart rate on depiction of the tagged region are discussed.     

Pathophysiology of adrenal hypertension.

Hypertension affects 20% to 25% of the adult population. Most patients are diagnosed as having essential or primary hypertension. Up to 10% to 15% have an identifiable cause and many of those have an adrenal basis. The identification of an adrenal cause of hypertension provides an opportunity for a targeted therapeutic intervention. Mineralocorticoid hypertension refers to hypertension caused by increased sodium and water retention by the kidney, expansion of the extracellular fluid compartment, and direct effects on the vasculature and circumventricular areas of the central nervous system (CNS), which result in elevation of blood pressure. The most common form of mineralocorticoid hypertension (MCH) is primary hyperaldosteronism (PA). In the past decade, significant advances have been made in our understanding of the pathogenesis of low-renin hypertension with the elucidation of the genetic basis and characterization of 3 forms of monogenic hypertension: glucocorticoid-remediable aldosteronism, syndrome of apparent mineralocorticoid excess, and Liddle's syndrome. This article focuses attention on the role of steroid hormones in the pathogenesis of hypertension and outlines the pathophysiology of the different forms of adrenal hypertension.     

Cooling effect of continuous renal replacement therapy in critically ill patients

Hypothermia is reported to increase intensive care unit (ICU) mortality. The heat loss that occurs during continuous renal replacement therapy (CRRT) favors the development of hypothermia. In an effort to assess the influence of CRRT on body temperature, we reviewed the records of 72 consecutive ICU patients treated with CRRT and further prospectively studied the temperature in the inlet and outlet lines for blood and dialysate of 27 other patients at various flow settings during continuous venovenous hemodialysis (CVVHD). Among the 72 retrospective cases, 36 episodes of hypothermia (core body temperature <35.5 degrees C) occurred and persisted for a mean of 2.6+/-1.8 days. It was more frequent during venovenous than arteriovenous modalities (31 of 67 v5 of 20, respectively); no patients developed hypothermia during arteriovenous slow continuous ultrafiltration (AVSCUS), whereas 48% of the patients undergoing CVVHD became hypothermic, occurring earlier in the therapy course (days 2 to 4). Mean arterial pressure (MAP) tended to increase after CRRT initiation, but absolute changes were not statistically significant. In the prospective arm, the CVVHD circuit temperatures were directly measured. Whereas no attempt was made to change body temperature, stepwise changes in blood (Qb) and dialysate flow rate (Qd) produced venous circuit temperature changes: the higher the Qb, the smaller the arteriovenous temperature differences independent of changes in Qd (P < 0.001). Also, venous circuit temperature varied directly with Qd at fixed Qb (P < 0.001). This relationship also held for temperature conversion to lost energy units per minute. Using room temperature dialysate, CRRT may significantly lower patients' core temperatures. Although the clinical significance of this effect is not clear at this point, energy loss during CVVHD may be important in hemodynamic stability or patient prognosis.     

Attenuation of Angiotensin II- and III-induced Aldosterone Release by Prostaglandin Synthesis Inhibitors

The effect of two prostaglandin synthesis inhibitors, indomethacin and meclofenamate, on angiotensin II (AII)- and III (AIII)-induced aldosterone release was studied in normal and sodium-depleted conscious rats and in adrenal capsular cell suspensions obtained from normal rats. In normal rats, in vivo AII and AIII were equipotent in causing dose-related increases in serum aldosterone concentrations. Indomethacin decreased the basal serum aldosterone levels by 50% and serum renin levels by 43%. In addition, the steroidogenic effects of AII and AIII were reduced by 45 and 63% with 3 mg/kg of indomethacin and 63 and 73% with 10 mg/kg, respectively. In contrast, meclofenamate failed to alter basal serum levels of aldosterone or AII-stimulated aldosterone release but inhibited serum renin levels by 27% and the aldosterone-stimulating effect of AIII by 99%. Indomethacin (3 mg/kg) and meclofenamate (2 mg/kg) inhibited urinary prostaglandin (PG)E(2) and PGF(2alpha) excretion by 63 and 52% and 37 and 31%, respectively. Both inhibitors significantly decreased the adrenal capsular PGE(2) and PGF(2alpha) content and the conversion of [(14)C]arachidonate to [(14)C]PGE(2) and [(14)C]PGF(2alpha). In sodium-depleted rats, indomethacin produced similar effects reducing the control serum aldosterone levels by 29%, AII-stimulated aldosterone by 47%, and completely suppressing the aldosterone response to AIII without altering serum renin activity. In adrenal cell suspensions, similar results were observed with indomethacin inhibiting basal and AII- and AIII-stimulated aldosterone release by 29, 81, and 93%, respectively. Meclofenamate failed to alter basal and AII-stimulated aldosterone release but inhibited that stimulated by AIII by 86%. The present findings suggest that prostaglandins modulate the effects of the renin-angiotensin system by stimulating the release of renin from the kidney and augmenting the steroidogenic effects of AII and AIII in the adrenal cortex.     

Design and preliminary evaluation of an expert system for platelet request evaluation

In spite of growing awareness of the potential risks associated with transfusion, the number of platelet units transfused in the United States continues to increase each year. There is a growing interest in ensuring that all transfusions are administered for appropriate reasons. Prospective review of requests for transfusions has been used to accomplish this goal. Although successful in reducing the number of inappropriate transfusions, this review method requires great time commitments by blood bank personnel and physicians. A knowledge-based system (ESPRE) that aids hospital blood bank personnel in the review of requests for platelet transfusions has been developed. The system automatically obtains most of the required patient data via a direct link to the hospital's main laboratory computers. The system generates a printed report that includes a list of patient-specific data, a list of the conditions for which a transfusion would be appropriate for the particular patient (given the clinical condition), and the conclusions drawn by the system. During a preliminary clinical evaluation of ESPRE, 73 randomly selected platelet transfusion requests were evaluated for approval by laboratory personnel and ESPRE. Overall, ESPRE would have approved 71 of the requests and laboratory staff would have approved 72. Forty-four percent of the requests would have been approved for the same reasons given by the staff. There were only three disagreements on final approval between ESPRE and blood bank personnel. This computerized expert system is a promising approach to the prospective review of all platelet transfusions.     

Circadian Rhythm of Plasma Aldosterone Concentration in Patients with Primary Aldosteronism

Plasma aldosterone, cortisol, and renin activity were measured in nine recumbent patients with hyperaldosteronism, including seven with adenomas, one with idiopathic hyperplasia, and one with glucocorticoid suppressible hyperplasia. All had peak values of plasma aldosterone concentration from 3 a.m. to noon and lowest values at 6 p.m. or midnight. This rhythm was similar to the circadian pattern of plasma cortisol in the same patients. When these data were normalized to eliminate the wide variation in ranges of plasma aldosterone and cortisol between individuals, there was an excellent correlation (r = + 0.87, P < 0.005) between the two hormones. In contrast, plasma aldosterone concentrations did not correlate with plasma renin activity before or after normalization of data.Short term suppression of ACTH by administration of dexamethasone eliminated the circadian variation of plasma aldosterone in both patients with hyperplasia and in four of five patients with adenomas, while it markedly altered the rhythm in the fifth. Similar doses of dexamethasone were administered to four normal subjects and did not flatten the circadian rhythm of plasma aldosterone.These data suggest that patients with primary aldosteronism have a circadian rhythm of plasma aldosterone mediated by changes in ACTH.     

Radioimmunoassay of myoglobin in human serum. Results in patients with acute myocardial infarction.

A radioimmunoassay has been developed for the measurement of serum myoglobin in order to evaluate the time-course and frequency of myoglobinemia in patients with acute myocardial infarction. The method can detect as little as 0.5 ng of myoglobin and is not affected by hemolysis or storage of serum at -- 20 degrees C. Myoglobin was detected in all of 92 sera from normal adults and ranged between 6 and 85 ng/ml. Levels were markedly elevated in sera from 18 of 20 patients with acute myocardial infarction when samples were obtained within 12 h after hospital admission, the mean concentration being 380+/-53 ng/ml. Wehn the initial sample was drawn between 12 and 24 h after admission in another group of 20 patients with acute myocardial infarcts, the mean serum myoglobin concentration was 195+/-47 ng/ml, and 11 of these individuals had normal levels. Serial determinations performed on nine patients with acute infarction demonstrated that maximum myoglobin levels occurred within the first 8-12 h after admission and fell rapidly toward normal thereafter. The serum concentration of myoglobin in 21 additional patients admitted with chest pain but without acute myocardial infarction was 41+/-6 ng/ml. Radioimmunoassay of serum myoglobin appears to be useful and sensitive test for the early detection of myocardial infarction.     

Gas chromatography/mass spectrometry characterization of corticosteroid metabolism in human immortalized keratinocytes

To continue our studies on the cutaneous expression of a proopiomelanocortin/corticotropin-releasing hormone system, we investigated whether this is accompanied by adrenal-type enzymatic activity. Immortalized cultured human keratinocytes were incubated with radiolabeled corticosteroids. Analysis by thin-layer chromatography showed rapid transformation of both progesterone and deoxycorticosterone; one of the progesterone metabolites migrated at the same rate as deoxycorticosterone. Gas chromatography/mass spectrometry further identified as major species of deoxycorticosterone metabolites 3beta,6alpha,21-trihydroxy-5alpha-pregnan-20-one, 3alpha,6alpha,21-trihydroxy-5alpha-pregnan-20-one, and 3alpha5alpha- and 3beta5alpha-tetrahydrodeoxycorticosterone. Minor metabolites were 3alpha,21-dihydroxy-5-pregnen-20- one (3alphaDelta5-21-OHpregnenolone), 3beta,21-dihydroxy-5-pregnen-20-one (3betaDelta5-21-OHpregnenolone), 3alpha,21-dihydroxy-4-pregnen-20-one (3alphaDelta4-21-OHpregnenolone), 6-hydroxy-dihydrodeoxycorticosterone, and two 5-dihydrodeoxycorticosterone species. Thus, in addition to sex steroids keratinocytes also actively metabolize corticosteroids along similar enzymatic pathways. The surprising detection of 3alphaDelta5-21-OHpregnenolone and 3 betaDelta5-21-OHpregnenolone, indicating Delta4-ketosteroids to Delta5-hydroxysteroids conversion, provides strong evidence for the occurrence, at least in human keratinocytes, of isomerase activity that allows the reaction to proceed in reverse of its usual direction. As skin expresses 3alpha/beta-hydroxysteroid dehydrogenase/Delta5-Delta4 isomerases, cutaneous reactions catalyzed by these enzymes must be reversible. In conclusion, besides elements of the corticotropin-releasing hormone/proopiomelanocortin system human keratinocytes show high levels of corticosteroid metabolizing activity. Moreover, the wide array of steroid products generated from a single substrate indicates serial progressive conversion involving 5alpha-reductase, 6alpha-hydroxylase, 3alpha/beta-hydroxysteroid dehydrogenase, and reverse Delta4minus signDelta5 isomerase enzymes. As distinct from the adrenal cortex, production of A, B, Aldo, 18OHdeoxycorticosterone, or F in keratinocytes was absent or below limits of detectability.