Risk factors associated with cytomegalovirus infection in heart transplant patients: a prospective, epidemiological study.

BACKGROUND: The objectives of this epidemiological, prospective study were to describe the characteristics of cytomegalovirus (CMV) infection in heart transplant (HT) recipients and to identify the variables that may influence the development of CMV viremia and CMV disease in these patients. METHODS: HT recipients ≥18 years of age (n=199) were included in the study. Variables studied included CMV serostatus, immunosuppressive treatment, and administration of anti-CMV prophylaxis. RESULTS: The mean age of the population was 52 years, and 84% were males. Immunosuppressive regimens were administered as induction therapy to 92.5% of patients; 88.5% of patients received calcineurin inhibitors as maintenance therapy. Anti-CMV treatment was given to 59% of 199 patients as prophylaxis (70%), preemptive therapy (10%), or to treat CMV infection (20%). Overall, 43% of patients had at least 1 positive viremia test. No patient with a high-risk serostatus (donor+/recipient-) receiving prophylaxis developed CMV syndrome, and only 2.5% of 199 patients developed CMV invasive disease. Multivariate analysis showed that having a positive donor CMV serostatus was associated with an increased risk of developing CMV viremia (P<0.012), while use of mammalian target of rapamycin (mTOR) inhibitors was associated with a decreased risk (P=0.005). CONCLUSIONS: In a population of HT recipients, the CMV infection rate was similar to that seen in previous studies, but the progression to overt CMV disease was very low. Having a CMV-positive donor was identified as an independent risk factor for developing CMV viremia, while the use of mTOR inhibitors was protective against viremia.

Malignancy after heart transplantation: incidence, prognosis and risk factors.

The Spanish Post-Heart-Transplant Tumour Registry comprises data on neoplasia following heart transplantation (HT) for all Spanish HT patients (1984-2003). This retrospective analysis of 3393 patients investigated the incidence and prognosis of neoplasia, and the influence of antiviral prophylaxis. About 50% of post-HT neoplasias were cutaneous, and 10% lymphomas. The cumulative incidence of skin cancers and other nonlymphoma cancers increased with age at HT and with time post-HT (from respectively 5.2 and 8.9 per 1000 person-years in the first year to 14.8 and 12.6 after 10 years), and was greater among men than women. None of these trends held for lymphomas. Induction therapy other than with IL2R-blockers generally increased the risk of neoplasia except when acyclovir was administered prophylactically during the first 3 months post-HT; prophylactic acyclovir halved the risk of lymphoma, regardless of other therapies. Institution of MMF during the first 3 months post-HT reduced the incidence of skin cancer independently of the effects of sex, age group, pre-HT smoking, use of tacrolimus in the first 3 months, induction treatment and antiviral treatment. Five-year survival rates after first tumor diagnosis were 74% for skin cancer, 20% for lymphoma and 32% for other tumors.

Three-dimensional echocardiography: in vivo validation for right ventricular free wall mass as an index of hypertrophy.

OBJECTIVES: This study tested the ability of three-dimensional echocardiography to reconstruct the right ventricular free wall and determine its mass in vivo using a system that automatically combines two-dimensional images with their spatial locations. BACKGROUND: Right ventricular free wall thickness is limited as an index of right ventricular hypertrophy because right ventricular mass may increase by dilation without increased thickness and because trabeculations and oblique views can exaggerate thickness in individual M-mode and two-dimensional scans. Three-dimensional echocardiography may have potential advantages because it can integrate the entire free wall mass, uninfluenced by oblique views or geometric assumptions. METHODS: The three-dimensional system was applied to 12 beating canine hearts to reconstruct the right ventricular free wall in intersecting views. The corresponding mass was compared with actual weights of the excised right ventricular free wall (15.5 to 78 g). For comparison, right ventricular sinus and outflow tract thickness were also measured by two-dimensional echocardiography, and the ability to predict mass from these values was determined. RESULTS: The three-dimensional algorithm successfully reproduced right ventricular free wall mass, which agreed well with actual values: y = 1.04x + 0.02, r = 0.985, SEE = 2.7 g (5.7% of the mean value). The two-dimensional predictions showed increased scatter: The variance of mass estimation, based on thickness, was 9.5 to 12.5 (average 11) times higher than the three-dimensional method (p < 0.02). CONCLUSIONS: Despite the irregular crescentic shape of the right ventricle, its free wall mass can be accurately measured by three-dimensional echocardiography in vivo, providing closer agreement with actual mass than predictions based on wall thickness. This method, with the increased efficiency of the three-dimensional system, can potentially improve our ability to evaluate the presence and progression of right ventricular hypertrophy.

Determinants of functional tricuspid regurgitation in incomplete tricuspid valve closure: Doppler color flow study of 109 patients.

OBJECTIVES: The aim of this study was to investigate the association between the pattern of incomplete tricuspid valve closure and the presence of tricuspid regurgitation and to identify factors that determine the severity of regurgitation associated with this pattern. BACKGROUND: The incomplete tricuspid valve closure pattern (defined as apical displacement of the leaflets) has been described by two-dimensional echocardiography. However, whether this pattern is universally associated with tricuspid regurgitation and the determinants of severity of regurgitation in its presence have not been studied by Doppler color flow mapping. METHODS: We identified 109 consecutive patients (mean age 62 +/- 17 years) with incomplete tricuspid valve closure who were studied by Doppler color flow mapping. We measured the linear apical displacement of the coaptation point from the tricuspid annulus and the area of displacement between the leaflets and annulus. Right atrial, ventricular and annular dimensions were measured and compared with those in a group of normal subjects. RESULTS: Tricuspid regurgitation was present in all patients with the incomplete closure pattern; it was mild in 14%, moderate in 19% and severe in 67%. Apical displacement was significantly greater (p < 0.02) in those with severe regurgitation than in those with mild regurgitation or in normal subjects. Tricuspid annulus dilation was the only independent predictor of severity of regurgitation. The right ventricle was not significantly dilated in 32% of patients, and right ventricular systolic pressure was not correlated with the severity of regurgitation and was < 30 mm Hg in 11% of patients. CONCLUSIONS: Tricuspid regurgitation was associated with incomplete tricuspid valve closure in all patients studied and was moderate to severe in 86%. Impaired coaptation is best reflected by the displacement area between the leaflets and the annulus. High pulmonary pressure and significant right ventricular dilation are not prerequisites for functional tricuspid regurgitation. Annular dilation is the most consistent and important determinant of this lesion.

New method for accurate calculation of regurgitant flow rate based on analysis of Doppler color flow maps of the proximal flow field. Validation in a canine model of mitral regurgitation with initial application in patients.

OBJECTIVES: The purpose of this study was to develop a rational and objective method for selecting a region in the proximal flow field where the hemispheric formula for calculating regurgitant flow rates by the flow convergence technique is most accurate. BACKGROUND: A major obstacle to clinical implementation of the proximal flow convergence method is that it assumes hemispheric isovelocity contours throughout the Doppler color flow map, whereas contour shape depends critically on location in the flow field. METHODS: Twenty mitral regurgitant flow rate stages were produced in six dogs by implanting grommet orifices into the anterior mitral leaflet and varying driving pressures so that actual peak flow rate could be determined from the known effective regurgitant orifice times the orifice velocity. Because plotting flow rate calculated by using a hemispheric formula versus alias velocities produces underestimation near the orifice and overestimation far from it, this plot was fitted to a polynomial function to allow identification of an inflection point within a relatively flat intermediate zone, where factors causing overestimation and underestimation are expected to be unimportant or balanced. The accuracy of flow rate calculation by the inflection point was compared with unselective and selective averaging techniques. Clinical relevance, initial feasibility and correlation with an independent measure were tested in 13 consecutive patients with mitral regurgitation who underwent cardiac catheterization. RESULTS: 1) The accuracy of single-point calculations was improved by selecting points in the flat portion of the curve (y = 1.15x - 3.34, r = 0.87, SEE = 22.1 ml/s vs. y = 1.34x - 1.99, r = 0.71, SEE = 45.6 ml/s, p < 0.01). 2) Selective averaging of points in the flat portion of the curve further improved accuracy and decreased scatter compared with unselective averaging (y = 1.08x + 4.8, r = 0.96, SEE = 11.6 ml/s vs. y = 1.30x + 0.6, r = 0.90, SEE = 20.9 ml/s, p < 0.01). 3) The proposed algorithm for mathematically identifying the inflection point provided the best results (y = 0.96x + 4.5, r = 0.96, SEE = 9.9 ml/s), with a mean error of 1.6 +/- 9.7 ml/s vs. 11.4 +/- 11.7 ml/s for selective averaging (p < 0.01). In patients, the proposed algorithm identified an inflection point at which calculated regurgitant volume agreed best with invasive measurements (y = 1.1x - 0.61, r = 0.93, SEE = 17 ml). CONCLUSIONS: The accuracy of the proximal flow convergence method can be significantly improved by analyzing the flow field mathematically to identify the optimal isovelocity zone before using the hemispheric formula to calculate regurgitant flow rates. Because the proposed algorithm is objective, operator independent and, thus, suitable for automatization, it could provide the clinician with a powerful quantitative tool to assess valvular regurgitation.

Quantification of pericardial effusions by three-dimensional echocardiography.

OBJECTIVES: The purpose of this study was to examine the accuracy of three-dimensional echocardiography for the quantification of asymmetric pericardial effusion volume and to compare this new technique with two-dimensional echocardiography. BACKGROUND: Quantification of pericardial effusion by two-dimensional echocardiography relies on a symmetric distribution of the fluid. Three-dimensional echocardiography can quantitate volume without these limitations, but its accuracy for pericardial effusion volume has not yet been assessed. METHODS: In six open chest dogs, 41 different asymmetrically distributed pericardial effusions of known volume were created by serial infusions of fluid through a pericardial catheter. The hearts were imaged using an automated echocardiographic method that integrates three-dimensional spatial and imaging data. The surfaces of the pericardial sac and heart were then reconstructed, and the volumes of pericardial effusions were calculated. Two-dimensional echocardiography was performed simultaneously, and volumes were calculated using the prolate ellipsoid method. Asymmetric distribution of the fluid was obtained by applying localized hydrostatic pressure to the pericardium. RESULTS: The volumes of pericardial effusion quantified using three-dimensional echocardiography correlated well with actual volumes (y = 1.0x - 1.4, SEE = 7.7 ml, r = 0.98). Two-dimensional echocardiography had an acceptable correlation (y = 1.0x + 2.3, SEE = 23 ml, r = 0.84), but a marked degree of variation from the true value was observed for any individual measurement. CONCLUSIONS: Three-dimensional echocardiography accurately quantifies pericardial effusion volume in vivo, even when the fluid is distributed asymmetrically, whereas two-dimensional echocardiography is less reliable. This new technique may be of clinical value in quantitating pericardial effusion, especially in the serial evaluation of asymmetric or loculated effusions.

Sirolimus as an alternative to anticalcineurin therapy in heart transplantation: experience of a single center.

We report a series of 26 heart transplant recipients with renal impairment in which sirolimus was used as the basic immunosuppresive drug (without associated calcineurin inhibitors) to avoid further nephrotoxicity. Sirolimus (trough levels 10 to 12 ng/mL, average daily dose 3 mg) was used in two settings: de novo in 7 patients with significant preexistent renal impairment and as a chronic conversion in 19 stable patients with established renal failure (creatinine level >2 mg/dL). In all de novo patients (n = 7), the renal function significantly improved. Creatinine fell from 2.95 +/- 0.9 mg/dL to 1.41 +/- 0.4 mg/dL at follow-up (P = .0017). One patient died suddenly of a massive pulmonary embolism. Only one patient experienced histologic but reversible rejection. In one patient, anemia and diarrhea prompted sirolimus withdrawal. Five patients had infectious episodes: three bacterial pneumonias, one mediastinitis, and two CMV infections. In the chronic conversion group (n = 19), the improvement was mostly limited to patients with moderate renal failure (creatinine < or =2.5 mg/dL) in which creatinine fell from 2.24 +/- 0.2 to 1.9 +/- 0.27 mg/dL, P = .009). When basal creatinine was over 2.5 mg/dL, only one third of the patients improved after conversion. Two patients died: terminal renal failure and cerebrovascular accident. There were no clinical episodes of rejection. Secondary effects prompted the discontinuation of sirolimus in five patients: two definite and one possible interstitial pneumonitis and two cases of anemia). The symptoms resolved after sirolimus withdrawal. Six patients had infection: four pneumonias, one sepsis, and one cutaneous abscess. Sirolimus is an interesting alternative to calcineurin inhibitors in selected patients with renal impairment. It prevents renal failure in de novo recipients at high risk of catastrophic renal damage and ameliorates renal dysfunction in chronic patients with moderate renal dysfunction. Given the high incidence of secondary effects, the adequate dosage and the secondary effects profile needs further study.

Hypocalcemia and pregnancy-induced hypertension produced by maternal fasting.

During pregnancy, maternal calcium needs increase as a result of increasing calcium requirements for fetal bone development. These needs have to be completely supplied by the mother via placental transfer. Several studies link low serum ionized calcium concentrations with the development of hypertension and pregnancy-induced hypertension. We hypothesized that maternal hypocalcemia would develop concomitantly with the development of hypertension in sheep that were fasted in late gestation. Sixteen instrumented ewes were used in the present study. After a 2-day baseline period, food was withdrawn from 10 animals in the experimental group (group 2) for 3 days, whereas the remaining six were allowed to eat and drink normally (group 1). Blood pressure, uteroplacental blood flow, and heart rate were monitored daily. Fasted animals were given deionized water (calcium free) to drink, whereas control animals were given tap water containing 32.9 mg/l calcium concentration. Based on the analysis of the ionized calcium concentration response to fasting, group 2 animals were placed in one of two groups: hypocalcemia did not develop in group 2a, whereas in group 2b the ionized calcium concentration decreased 27% (from 1.09 +/- 0.07 to 0.80 +/- 0.06 mM, p = 0.01) by the third day of fasting. Group 2b responded with a 16% elevation in maternal blood pressure (p = 0.01) and a 43% reduction in uteroplacental blood flow. Furthermore, a positive correlation was found between maternal and fetal blood ionized calcium concentrations (r = 0.860).(ABSTRACT TRUNCATED AT 250 WORDS)

Hypocalcemia and pregnancy-induced hypertension produced by low-calcium diet.

Recent studies from our laboratory in fasting pregnant ewes with twin gestation have implicated low serum calcium concentration in the etiology of hypertension in pregnancy. We hypothesized that the reduction in serum calcium concentration produced by feeding of a calcium-deficient diet in twin gestation would lead to a significant increase in maternal arterial blood pressure, vascular resistance, and protein in the urine and decreased uterine blood flow. Twenty-five instrumented ewes were used in the present study. After surgery a calcium-deficient diet and deionized water (calcium ion free) were provided ad libitum to 19 animals. Blood pressure, cardiac output, heart rate, and uterine blood flow were monitored every other day. Six control animals were provided with standard Rumilab diet and tap water (group 1). Animals on a low-calcium diet (group 2) were subdivided according to the blood ionized calcium response to low dietary calcium intake. Non-hypocalcemic animals were assigned to group 2a (n = 10), and hypocalcemic animals (calcium concentration below two standard deviations from the control group) were assigned to group 2b (n = 9). In group 2b calcium concentration decreased from 1.03 +/- 0.04 mmol/L on day 110 of gestation to 0.77 +/- 0.03 mmol/L by day 125 of gestation. Arterial blood pressure increased significantly from 76 +/- 2 to 91 +/- 2 mm Hg, and uterine blood flow decreased from 950 +/- 53 to 579 +/- 48 mL/min. Urinary protein increased from 1.7 +/- 0.3 to 10.5 +/- 1.2 g/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of Doppler-determined elevated pulmonary arterial pressure with pressure measured at cardiac catheterization.

This study assesses use of pulsed Doppler echocardiography to measure pulmonary artery (PA) pressure. PA flow at the right ventricular (RV) outflow tract was analyzed in 51 patients. Attention was focused on PA flow morphologic pattern, RV systolic intervals, time to peak flow and acceleration time index. Correlation was made with PA pressure and total pulmonary resistance. Three morphologic patterns of PA flow were found: type I indicates normal PA pressure (sensitivity 85%, specificity 100%) and types II and III indicate PA hypertension (sensitivity 100%, specificity 85%). The RV preejection/RV ejection ratio, time to peak flow and acceleration time index show a good correlation coefficient improved when a logarithmic function was applied. The best correlation was achieved with time to peak flow (r = -0.77 with PA pressure, r = -0.79 with total pulmonary resistance), and especially with acceleration time index (r = -0.84 with PA pressure, r = -0.87 with total pulmonary resistance). Analysis of pulmonary flow is a reliable new tool for evaluating PA pressure and is even better for evaluating total pulmonary resistance. Acceleration time index is the parameter that correlates best with these 2 variables.

Which physical factors determine tricuspid regurgitation jet area in the clinical setting?

The visual assessment of jet area has become the most common method used in daily clinic practice to evaluate valvular regurgitation. Despite the high prevalence of tricuspid regurgitation, however, few studies have systematically compared TR jet areas with a quantitative standard. To evaluate this, 40 patients in sinus rhythm with tricuspid regurgitation were analyzed: 16 with centrally directed free jets and 24 with impinging wall jets. The size of the maximal planimetered color jet area (cm2) was compared with parameters derived using the pulsed Doppler 2-dimensional echocardiographic method: regurgitant fraction and the flow convergence method (peak flow rate, effective regurgitant orifice area and momentum). Mean tricuspid regurgitant fraction averaged 33 +/- 15%, peak flow rate 76 +/- 54 cm3/s, effective regurgitant orifice area 27 +/- 21 mm2 and momentum 21,717 +/- 15,014 cm4/s2. An average of 4-chamber, and long- and short-axis areas in free jets correlated well with regurgitant fraction (r = 0.81, p < 0.001), better with peak flow rate (r = 0.94, p < 0.001), effective regurgitant orifice (r = 0.92, p < 0.001) and momentum (r = 0.94, p < 0.001). The correlation was worse, but still significant, in wall jets. For the same peak flow rate, wall jets were 75% of the size of a corresponding free jet. Jet area measurement is a good semiquantitative tool to measure tricuspid regurgitation in free jets, which correlates well with regurgitant fraction and better with new parameters available from analysis of the proximal acceleration field. In patients with eccentrically directed wall jets the correlation with planimetered jet area was worse, but still significant.

Perivalvular abscesses associated with endocarditis. Clinical features and diagnostic accuracy of two-dimensional echocardiography.

OBJECTIVE: To determine the clinical implications of the development of a perivalvular abscess in the course of an infective endocarditis and evaluate the utility of two-dimensional echocardiography in the diagnosis of this complication. DESIGN: Retrospective clinical review. Investigator-blinded comparative echographic case-control study. SETTING: Tertiary referral center. PATIENTS: Forty patients with infective endocarditis and a histologically proved diagnosis of perivalvular abscess. INTERVENTION: Two-dimensional echocardiograms corresponding to 36 of these 40 patients were blindly compared with two-dimensional echocardiograms of 20 randomly chosen patients with infective endocarditis in whom myocardial abscesses had not been demonstrated during surgery. MEASUREMENTS AND MAIN RESULTS: During surgery or at autopsy, 40 patients had a total of 41 definite perivalvular abscesses. Native valve endocarditis was present in 27 patients, and prosthetic valve endocarditis was present in 13 patients. Abscesses were more frequent in aortic-valve endocarditis (57.5 percent) than in infections of other valves, and the infecting organism was more often Staphylococcus (42.5 percent of cases). The hospital mortality rate was 90 percent in the 10 patients who did not receive surgical treatment, as compared with 26.6 percent in the 30 operated-on patient (p < 0.001). Sensitivity and specificity for the detection of abscesses associated with endocarditis were 80.5 percent and 85 percent, respectively, for transthoracic two-dimensional echocardiography. CONCLUSIONS: Our data indicate that transthoracic echocardiography remains an accurate method for the diagnosis of abscesses associated with endocarditis, even in the presence of a prosthetic valve, and it could help to indicate early surgery in these patients.

Color Doppler diagnosis of left ventricular pseudoaneurysm.

A patient underwent mitral valve replacement because of mitral insufficiency secondary to bacterial endocarditis. Early postoperatively, routine examination with "color Doppler" correctly identified the presence of a left ventricular pseudoaneurysm. To our knowledge, this is the first case of left ventricular pseudoaneurysm diagnosed by this new technique.

Characteristics of chronic self-administration of morphine by dogs.

Each of five dogs that had been trained to chronically self-administer IV morphine was tested with changes in the morphine dose from the baseline dose (1 mg/kg/infusion) to 0.125, 0.5, or 2 mg/kg/infusion, and with passive administration of the usual daily morphine intake while either continuing the morphine self-administration at the baseline dose or changing the self-administered solution to saline. Each treatment lasted 5 weeks. Results indicated that there is a significant negative regression of response on dose, and chronic self-administration of morphine is not entirely accounted for by a need to avoid abstinence or to obtain a direct drug effect. A third element, which may be an acquired need to obtain a response-contingent drug effect, is necessary to account for the chronic self-administration of morphine by the dog.

Effects of methadone and morphine maintenance on drug-seeking behavior in the dog.

The effects of methadone and morphine maintenance on morphine self-administration were studied in the dog. Methadone was given passively for 2 weeks by continuous i.v. infusion. The amount of methadone administered daily was the same in mg/kg as the mean daily mg/kg of morphine the dogs had self-administered during the premaintenance control week. Morphine self-administration was markedly reduced initially but returned to normal levels within 2 weeks of methadone administration. Following the methadone maintenance period, morphine self-administration was increased over the premaintenance period for 2 weeks. A result similar to that with methadone was obtained in a second experiment when morphine was used as the maintenance drug in an amount that was three times the amount the dogs had been self-administering during the premaintenance control week.

Stereoselective behavioral effects of N6-phenylisopropyl-adenosine and antagonism by caffeine.

Effects of the (-)- and (+)-isomers of N6-(phenylisopropyl)-adenosine (PIA) were studied in rats trained to respond under fixed-interval and fixed-ratio schedules of food reinforcement. Both isomers of PIA decreased response rates; however, the (-)-isomer decreased response rates at doses as low as 0.1 microM/kg and was 100-300 times more potent than the (+)-isomer. The potency differences suggest that the effects observed were due to actions at A1-adenosine receptors. Caffeine, an adenosine-receptor antagonist, when administered alone in doses of 10-154 microM/kg, increased response rates under the fixed-interval schedule and did not affect rates of responding under the fixed-ratio schedule. Higher doses decreased response rates under both schedules. Caffeine shifted the (-)-PIA dose-effect curve to the right. At a low dose of caffeine (25.7 microM/kg), which alone modestly increased response rates under the 5-min fixed-interval schedule, the disruptions in rates and patterns of responding produced by (-)-PIA were restored to resemble control performances. The higher dose of caffeine (77.2 microM/kg), which alone produced larger increases in rates of responding under the fixed-interval schedule, restored overall response rates to control levels when administered in combination with (-)-PIA. However, patterns of responding after the combination of doses remained disrupted. These effects suggest that some of the behavioral effects of caffeine are a result of mechanisms other than adenosine-receptor blockade.

A method for bioassay of physical dependence on sedative drugs in dog.

A method for an economical bioassay of physical dependence on sedatives is presented. Dogs maintained on sodium pentobarbital (200 mg/kg/24 h i.v.) were given periodic graded reductions in maintenance dose, and subscales for measuring signs of abstinence were developed. Using these subscales the relative potencies compared with sodium pentobarbital were determined for sodium secobarbital (RP = 0.85) and methaqualone (RP = 0.14). Sodium thiopental and methaqualone were assayed and found to be equipotent (RP = 0.96) in reducing the signs of abstinence from sodium pentobarbital. The occurrence of convulsions, during periods of complete reduction of the maintenance drug, became less frequent the longer the dogs had been maintained on a constant dose of sodium pentobarbital.

Generalization of drug-seeking behavior in dogs.

Drug-naive dogs which do not spontaneously initiate morphine self-administration were given one of three treatments and tested for subsequent morphine self-administration. Neither the dogs given the treatment of response-contingent drinking water nor those given d-amphetamine by passive infusions subsequently showed significant self-administration of morphine. However, the third group which self-administered d-amphetamine did subsequently self-administer morphine. The data suggest that self-administration of one reinforcing psychoactive drug may increase the probability of subsequently self-administering another.

Drug-seeking behavior in the dog: lack of effect of prior passive dependence on morphine.

Twelve dogs were made dependent on morphine (20 mg/kg per 24 hours) by intravenous passive administration of the drug. Six were gradually withdrawn and six were withdrawn abruptly. Subsequent tests for self-administration of morphine began within 8 to 18 weeks after morphine was last administered passively. Morphine was available for self-administration at several unit dose levels for 8 weeks. In comparison with control dogs administered with saline, there was no evidence that prior dependence on morphine influences subsequent self-administration of morphine, or that morphine is a primary reinforcer for dogs. Possible implications of these and related observations are discussed.

Pregnant adolescent and adult women have similarly low intakes of selected nutrients.

OBJECTIVE: To examine the dietary intake of pregnant adolescents during the second and third trimester of pregnancy, and to compare their nutrient intake with that of pregnant adults. DESIGN: Two 7-day food records (14 days) from subjects participating in a larger randomized clinical calcium trial: the first at 19 to 21 weeks and the second between 29 and 31 weeks gestation. Intake of energy and selected nutrients were calculated and compared with dietary standards. SUBJECTS/SETTING: Fifty-nine pregnant adolescents and 97 pregnant adults recruited from prenatal clinics at a metropolitan university hospital. STATISTICAL ANALYSES: Two sample t tests, equality of variances, and repeated measures (analysis of variance). RESULTS: There was no difference in mean nutrient intakes between the second and third trimesters. Using two 7-day food records, we found mean intakes for energy, iron, zinc, calcium, magnesium, folate, and vitamins D and E to be below recommended standards in both groups. Other nutrients examined met or exceeded reference values. Total daily intakes for energy and 11 nutrients were significantly higher in the adolescent compared to the adult diets (P < .05). These differences were not evident when nutrient values were corrected for energy, indicating that increased energy intake in the teen-aged population was contributed by nutrient-dense foods. APPLICATIONS: This study indicates the need for continued dietary monitoring of pregnant adolescents and pregnant adults, including nutrition guidance that stresses food sources of calcium, magnesium, zinc, iron, fiber, folate, and vitamins D and E, the nutrients found deficient in their diets.