Maternal periconceptional biochemical and hematological parameters, vitamin profiles and pregnancy outcome.

OBJECTIVES: To evaluate periconceptional maternal biochemical and hematological parameters and vitamin profiles in relation to the risk of early pregnancy loss and birth weight. DESIGN: Prospective longitudinal study. SETTING: University Medical Centre Nijmegen, Academic Medical Centre, Amsterdam, Maria and Elisabeth Hospitals, Tilburg, and Catharina Hospital, Eindhoven, The Netherlands. SUBJECTS: A cohort of 240 women recruited before pregnancy. INTERVENTIONS: Blood samples were taken preconceptional and at 6 and 10 weeks amenorrhea in which the concentrations of hemoglobin, hematocrit, creatinin, uric acid, total protein, serum iron, total iron-binding capacity, ferritin, and the concentrations of retinol, tocopherol, thiamine, riboflavin, pyridoxal-5'-phosphate, cobalamin and folate were analyzed. MAIN OUTCOME MEASURES: Risk of early pregnancy loss and birth weight. RESULTS: The risk of early pregnancy loss increased with increasing prepregnancy weight, and when the periconceptional decline in hematocrit, creatinin and uric acid was less profound (slope: P<0.01). Maternal smoking was negatively associated with birth weight (mean reduction of 183 g, P<0.05). Maternal age and prepregnancy weight were positively associated with birth weight (P<0.01). No significant associations were found between vitamin concentrations and risk of early pregnancy loss or birth weight. CONCLUSIONS: Several periconceptional biochemical parameters are significantly associated with early pregnancy loss. The effects of maternal periconceptional health on embryonic development and subsequent pregnancy outcome should be further explored. SPONSORSHIP: Dutch Prevention fund, grants no. 28.1358 and 28.1006.

Clinical significance of reverse redistribution on technetium-99m tetrofosmin single-photon emission computed tomography: an 18-month follow-up study.

BACKGROUND: The clinical and prognostic significance of reverse redistribution on technetium-99m (99mTc) single-photon emission computed tomography (SPECT) is unclear. OBJECTIVES: To determine outcomes of chest pain patients showing reverse redistribution after 99mTc tetrofosmin SPECT versus SPECT showing no reverse redistribution. METHODS: Patient outcomes (death, nonfatal myocardial infarction, coronary artery bypass grafting and percutaneous transluminal coronary angioplasty) within 18 months after 99mTc tetrofosmin SPECT were determined in two populations of ambulatory patients, most of whom had been evaluated because of chest pain: a population of 57 patients whose SPECT images showed reverse redistribution without reversible or fixed defects, versus a control population of 98 patients whose SPECT images were normal (no reverse redistribution, no reversible defects, no fixed defects). RESULTS: Stepwise logistic regression analysis showed that the population of patients with reverse redistribution did not have a worse 18-month outcome in comparison with the control population of patients without reverse redistribution (3.5% versus 9.2%, respectively; p=0.15 corrected for age and gender). CONCLUSION: Reverse redistribution on 99mTc tetrofosmin SPECT does not appear to be an unfavourable prognostic factor in ambulatory chest pain patients.

Homocysteine and folate status in methotrexate-treated patients with rheumatoid arthritis.

OBJECTIVE: To study (i) the influence of methotrexate (MTX) therapy on homocysteine and folate metabolism in patients with rheumatoid arthritis (RA), (ii) the influence of the C677T mutation in the methylenetetrahydrofolate reductase gene (MTHFR) on the change in plasma homocysteine levels during MTX treatment, and (iii) the interference of folate and homocysteine metabolism with the efficacy and toxicity of treatment with MTX. METHODS: The 113 patients enrolled in this study were participating in a 48-week, multicentre, double-blind, placebo-controlled study comparing the efficacy and toxicity of MTX treatment with and without folic or folinic acid supplementation. The MTX dose was 7.5 mg/week initially and increased to a maximum of 25 mg/week if necessary. Concentrations of total folate, 5-methyl tetrahydrofolate (in serum and in erythrocytes) and of homocysteine, cysteine and cysteine-glycine and the MTHFR genotype were determined before the start of the study, after 6 weeks, and after 48 weeks or on withdrawal from the study. Blood was drawn from fasting patients at a standardized time in the morning, 16 h after intake of MTX. The laboratory results were related to parameters of efficacy and toxicity of MTX treatment. RESULTS: Baseline values were distributed equally in the three treatment groups. The mean plasma homocysteine level (normal range 6-15 micromol/l) before the start of MTX was relatively high in all groups: 15.4 micromol/l [95% confidence interval (CI) 13.5 to 17.2] in the MTX plus placebo group (n=39), 14.3 micromol/l (95% CI 12.2 to 16.4) in the MTX plus folic acid group (n=35) and 15.9 micromol/l (95% CI 13.7 to 18.1) in the MTX plus folinic acid group (n=39). After 48 weeks of MTX therapy, the mean homocysteine level showed an increase in the placebo group (+3.6 micromol/l, 95% CI 1.7 to 5.6). In contrast, a decrease was observed in the groups supplemented with folic or folinic acid (folic acid, -2.7 micromol/l, 95% CI -1.4 to -4.0; folinic acid, -1.6 micromol/l, 95% CI -0.1 to -3.0). The differences in the change in plasma homocysteine level between the placebo group and each of the two folate-supplemented groups were statistically significant (P<0.0001), contrary to the difference between the folic and folinic acid groups (P=0.26). Linear regression analysis showed that the change in plasma homocysteine level was statistically significantly associated with folic or folinic acid supplementation (P=0.0001) but not with the presence or absence of the C677T mutation in the MTHFR gene. Homozygous mutants had a higher plasma homocysteine concentration at baseline. No relationship was found between the change in disease activity and the change in homocysteine concentration or the mean homocysteine concentration after 48 weeks of MTX therapy. Toxicity-related discontinuation of MTX treatment was not associated with the change in homocysteine concentration. CONCLUSIONS: Low-dose MTX treatment in RA patients leads to an increased plasma homocysteine level. Concomitant folate supplementation with either folic or folinic acid decreases the plasma homocysteine level and consequently protects against potential cardiovascular risks. No relationship was found between the change in homocysteine concentration and the presence or absence of the C677T mutation in the MTHFR gene. Homocysteine metabolism was not associated with efficacy or toxicity of MTX treatment.

The C677T mutation in the methylenetetrahydrofolate reductase gene: a genetic risk factor for methotrexate-related elevation of liver enzymes in rheumatoid arthritis patients.

OBJECTIVE: To study the possible relationship between the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene and the toxicity and efficacy of treatment with methotrexate (MTX) in patients with rheumatoid arthritis (RA). METHODS: Genotype analysis of the MTHFR gene was done in 236 patients who started MTX treatment with (n = 157) or without (n = 79) folic or folinic acid supplementation. Outcomes were parameters of efficacy of MTX treatment, patient withdrawal due to adverse events, discontinuation of MTX treatment because of elevated liver enzyme levels, and the total occurrence of elevated liver enzyme levels during the study. Multivariate logistic regression analysis was used to study the relationship between the presence of the MTHFR C677T mutation and toxicity outcomes of MTX treatment. RESULTS: Forty-eight percent of the patients showed the homozygous (T/T) or heterozygous (T/C) mutation. The presence of the C677CT or C677TT genotypes was associated with an increased risk of discontinuing MTX treatment because of adverse events (relative risk 2.01; 95% confidence interval 1.09, 3.70), mainly due to an increased risk of elevated liver enzyme levels (relative risk 2.38; 95% confidence interval 1.06, 5.34). Efficacy parameters were not significantly different between the patients with and those without the mutation. CONCLUSION: The C677T mutation is the first identified genetic risk factor for elevated alanine aminotransferase values during MTX treatment in patients with RA. We postulate that the incidence of clinically important elevation of liver enzyme levels during MTX treatment is mediated by homocysteine metabolism. Supplementation with folic or folinic acid reduced the risk of toxicity-related discontinuation of MTX treatment both in patients with and in patients without the mutation.

Influence of sex, age, and menopausal state on the course of early rheumatoid arthritis.

OBJECTIVE: To investigate the influences of the menopausal state, sex, and age on the course and outcome of rheumatoid arthritis (RA). METHODS: A cohort of patients with early RA (209 female, 123 male) was studied. Sex, age, and menopausal state at baseline, and disease activity, radiographic joint destruction, and physical disability during 6 years of followup were assessed. RESULTS: The Disease Activity Score (DAS) was significantly higher in female compared to male patients at any time point except at the time of inclusion. This was mainly due to postmenopausal patients. Radiographic joint destruction (RJD) was significantly worse in female patients compared to males at the time of inclusion. Postmenopausal patients had significantly higher RJD than premenopausal patients at the time of inclusion and 3 years thereafter. Older male patients showed worse RJD than younger male patients at all time points measured. Physical disability was significantly worse in female compared to male patients, as well as in postmenopausal compared to premenopausal patients, and older male compared to younger male patients. Stepwise regression analysis revealed that at 3 years higher age and female sex were the best predictors for a worse DAS. Higher age and the interaction term between menopausal state and age best predicted higher RJD. Higher age and the interaction term between menopausal state and age best predicted Health Assessment Questionnaire (HAQ) score. CONCLUSION: Higher age at presentation of RA leads to a more severe disease course in terms of DAS, RJD, and HAQ. Although female sex has a deteriorating effect on the DAS, the menopausal state is responsible for the major part of the differences in outcome between men and women. Postmenopausal state in early RA influences future disability and damage, especially in older patients.

Effect of folic or folinic acid supplementation on the toxicity and efficacy of methotrexate in rheumatoid arthritis: a forty-eight week, multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: To study the effect of folates on discontinuation of methotrexate (MTX) as single-drug antirheumatic treatment due to toxicity, to determine which type of adverse events are reduced, to study the effects on the efficacy of MTX, and to compare folic with folinic acid supplementation in a 48-week, randomized, double-blind, placebo-controlled trial. METHODS: Patients with active RA (n = 434) were randomly assigned to receive MTX plus either placebo, folic acid (1 mg/day), or folinic acid (2.5 mg/week). The initial MTX dosage was 7.5 mg/week; dosage increases were allowed up to a maximum of 25 mg/week for insufficient responses. Folate dosages were doubled once the dosage of MTX reached 15 mg/week. The primary end point was MTX withdrawal because of adverse events. Secondary end points were the MTX dosage and parameters of efficacy and toxicity of MTX. RESULTS: Toxicity-related discontinuation of MTX occurred in 38% of the placebo group, 17% of the folic acid group, and 12% of the folinic acid group. These between-group differences were explained by a decreased incidence of elevated liver enzyme levels in the folate supplementation groups. No between-group differences were found in the frequency of other adverse events or in the duration of adverse events. Parameters of disease activity improved equally in all groups. Mean dosages of MTX at the end of the study were lower in the placebo group (14.5 mg/week) than in the folic and folinic acid groups (18.0 and 16.4 mg/week, respectively). CONCLUSION: Both folate supplementation regimens reduced the incidence of elevated liver enzyme levels during MTX therapy, and as a consequence, MTX was discontinued less frequently in these patients. Folates seem to have no effect on the incidence, severity, and duration of other adverse events, including gastrointestinal and mucosal side effects. Slightly higher dosages of MTX were prescribed to obtain similar improvement in disease activity in the folate supplementation groups.

Cognitive behaviour therapy for chronic fatigue syndrome: a multicentre randomised controlled trial.

BACKGROUND: Cognitive behaviour therapy (CBT) seems a promising treatment for chronic fatigue syndrome (CFS), but the applicability of this treatment outside specialised settings has been questioned. We compared CBT with guided support groups and the natural course in a randomised trial at three centres. METHODS: Of 476 patients diagnosed with CFS, 278 were eligible and willing to take part. 93 were randomly assigned CBT (administered by 13 therapists recently trained in this technique for CFS), 94 were assigned the support-group approach, and 91 the control natural course. Multidimensional assessments were done at baseline, 8 months, and 14 months. The primary outcome variables were fatigue severity (on the checklist individual strength) and functional impairment (on the sickness impact profile) at 8 and 14 months. Data were analysed by intention to treat. FINDINGS: 241 patients had complete data (83 CBT, 80 support groups, 78 natural course) at 8 months. At 14 months CBT was significantly more effective than both control conditions for fatigue severity (CBT vs support groups 5.8 [2.2-9.4]; CBT vs natural course 5.6 [2.1-9.0]) and for functional impairment (CBT vs support groups 263 [38-488]; CBT vs natural course 222 [3-441]). Support groups were not more effective for CFS patients than the natural course. Among the CBT group, clinically significant improvement was seen in fatigue severity for 20 of 58 (35%), in Karnofsky performance status for 28 of 57 (49%), and self-rated improvement for 29 of 58 (50%). Prognostic factors for outcome after CBT were a higher sense of control predicting more improvement, and a passive activity pattern and focusing on bodily symptoms predicting less improvement. INTERPRETATION: CBT was more effective than guided support groups and the natural course in a multicentre trial with many therapists. Our study showed a lower proportion of patients with improvement than CBT trials with a few highly skilled therapists.

Longitudinal vitamin and homocysteine levels in normal pregnancy.

Evidence of the impact of maternal nutritional status on pregnancy outcome is increasing. However, reference values for vitamin and homocysteine concentrations in maternal blood during normal pregnancy are scarce, and are lacking for the preconceptional period and early pregnancy. Thus, in a longitudinal study we evaluated vitamin and homocysteine concentrations in 102 nulliparous women with an uneventful singleton pregnancy and normal outcome not using supplements. The physiological changes in vitamin and homocysteine concentrations in blood were determined from the preconceptional period throughout pregnancy until 6 weeks post-partum. The vitamins evaluated comprised retinol, thiamin, riboflavin, pyridoxal 5'-phosphate, folate in serum and erythrocytes, vitamin B12 and alpha-tocopherol. The plasma homocysteine concentration was also measured, considering the essential roles of folate, vitamin B6 and vitamin B12 in homocysteine metabolism. The concentrations of retinol, thiamin, pyridoxal 5'-phosphate serum folate and vitamin B12 decreased during pregnancy. In contrast, the concentrations of riboflavin, alpha-tocopherol, and folate in erythrocytes increased or showed only minor changes. Homocysteine concentrations also remained approximately constant during pregnancy. These observations emphasize the importance of preconceptional and post-partum concentrations of vitamins in the evaluation of pregnancy-induced changes. These data have provided valuable reference values for vitamins and homocysteine before, during and after pregnancy in order to contribute to better diagnosis of maternal deficiencies and to study further the relationship between maternal vitamin status and adverse course and outcome of pregnancy.

Venous reflux has a limited effect on calf muscle pump dysfunction in post-thrombotic patients.

The purpose of the present study was to evaluate the relationship between calf muscle pump dysfunction (CMD) and the presence and location of valvular incompetence. Deep vein obstruction might influence CMD, and so venous outflow resistance (VOR) was measured. VOR and calf muscle pump function were measured in 81 patients, 7-13 years after venographically confirmed lower-extremity deep venous thrombosis. The supine venous pump function test (SVPT) measures CMD, and the VOR measures the presence of venous outflow obstructions, both with the use of strain-gauge plethysmography. Valvular incompetence was measured using duplex scanning in 16 vein segments of one leg. Venous reflux was measured in proximal veins using the Valsalva manoeuvre, and in the distal veins by distal manual compression with sudden release. Abnormal proximal venous reflux was defined as a reflux time of more than 1 s, and abnormal distal venous reflux as a reflux time of more than 0.5 s. No statistically significant relationship was found between the SVPT and either the location or the number of vein segments with reflux. Of the 81 patients, only nine still had an abnormally high VOR, and this VOR showed no relationship with the SVPT. In conclusion, venous reflux has a limited effect on CMD, as measured by the SVPT. The presence of a venous outflow obstruction did not significantly influence the SVPT. Duplex scanning and the SVPT are independent complementary tests for evaluating chronic venous insufficiency.

Photorefractive keratectomy with an ablatable mask for myopic astigmatism.

PURPOSE: To evaluate efficacy, safety, and stability of photoastigmatic keratectomy (PARK) carried out with a Summit Apex Plus laser using an ablatable mask. METHODS: Forty-one eyes of 41 patients with myopic astigmatism with follow-up of 12 months were evaluated. Treatment efficacy was compared in groups with high (>6.00 D) versus low (< or =6.00 D) preoperative spherical equivalent subjective manifest refraction, in groups with high (>2.00 D) versus low (< or =2.00 D) preoperative cylindrical component and in groups divided according to preoperative axis of cylinder. RESULTS: At 12 months after surgery, mean spherical equivalent manifest refraction in all 41 eyes was -0.30 +/- 0.90 D. Mean cylinder component was 0.60 +/- 0.70 D. Mean reduction in astigmatic component was 67 +/- 47%. Uncorrected visual acuity of 0.5 or more was achieved in 79% of eyes; 71% of eyes achieved 0.8 or more. At 1 month after surgery, 49% of eyes had a loss of 2 or more lines of spectacle-corrected visual acuity. This loss was restored at 12 months. No statistically significant differences were found between the different subgroups. CONCLUSION: Photoastigmatic keratectomy with ablatable mask gives satisfactory results. No relation in efficacy was found when taking into account the amount of preoperative spherical component, the cylindrical component, or the cylinder axis direction.

Uncertainty of incremental cost-effectiveness ratios. A comparison of Fieller and bootstrap confidence intervals.

OBJECTIVE: To compare different methods to estimate the confidence interval of the incremental cost-effectiveness ratio (ICER). METHODS: The adequacy of Fieller intervals and three methods for calculating bootstrap intervals are compared based on a simulation of 10,000 trials, using data from one trial. RESULTS: Both Fieller and bootstrap methods lead to unsatisfactory results when the difference in effectiveness is approximately zero. Where this difference is significant, the four methods for calculating confidence intervals for ICER do not give very different results, but Fieller's interval performs best. CONCLUSIONS: Since Fieller's confidence limits are relatively easy to compute compared with bootstrap simulations, we recommend using this method.

[Results of photorefractive keratectomy using the excimer laser in the treatment of myopia; 1-year follow-up]. / Resultaten van fotorefractieve keratectomie met de excimer-laser ter behandeling van myopie; 1 jaar follow-up.

OBJECTIVE: Evaluation of the first excimer laser treatments of myopia. DESIGN: Descriptive. SETTING: Excimer Laser Centrum, Department of Ophthalmology, University of Nijmegen, Nijmegen, the Netherlands. METHOD: 312 patients underwent spherical excimer laser treatment to correct myopia of 1.2 up to 10 diopters between February 1992 and October 1993. 245 patients completed a follow-up of one year or more; 36 retreatments were carried out. Group I (treatment 1.2 to 6 D) numbered 174 patients, group II (6.1-10 D) 71 patients. RESULTS: After a follow-up period of one year or just before retreatment 79% of group I and 48% of group II achieved a refractive correction within 1 D of the attempted correction. Visual acuity without correction was 0.5 or more in 94% of group I and in 76% of group II. Less than one percent (n = 1) of group I and 6% (n = 4) of group II lost more than one line of best corrected visual acuity. Retreatment could correct 50% of those eyes that did not achieve a refraction within 1 D of attempted correction. Loss of visual acuity was corrected by retreatment in 5 of 6 cases of group I and in 7 of 11 cases of group II. CONCLUSION: Based on a one-year follow-up, refractive surgery with the excimer laser appears to correct myopia between 1 and 10 D effectively. Predictability is diminishing on correcting higher amounts of refractive error. Thorough information of the patients regarding the results to be expected will prevent disappointment.

Effects of chlormadinone acetate, acetazolamide and oxygen on awake and asleep gas exchange in patients with chronic obstructive pulmonary disease (COPD).

The purpose of this study was to assess the short-term effects of chlormadinone acetate (CMA), a synthetic progestogen, acetazolamide (ACET) and oxygen on awake and asleep blood gas values. The study was conducted according to a randomized, double-blind and placebo-controlled design in 53 hypoxaemic patients with chronic obstructive pulmonary disease. On the first two consecutive nights, all patients received either room air or oxygen, via a nasal cannula, in random order. They then received either CMA (25 mg), ACET (250 mg) or placebo twice a day, all in identical capsules. On the third study night, after one week of drug treatment, the patients were tested breathing room air. CMA and ACET therapy decreased mean daytime arterial carbon dioxide tension (PaCO2) by 0.7 and 0.5 kPa, respectively, and night-time end-tidal carbon dioxide tension (PETCO2) by 0.5 and 0.3 kPa, respectively. Supplemental oxygen caused increased CO2 retention during the day and night (0.6 and 0.3 kPa, respectively. Daytime arterial oxygen tension (PaO2) increased to the same extent during ACET (1.9 kPa) and oxygen (2.5 kPa). Asleep oxygen saturation improved most with oxygen supplementation (7%), although ACET also caused significant improvement (4%). CMA administration had virtually no effect on mean awake and asleep hypoxaemia. ACET therapy significantly improved subjective sleep quality. On CMA, minute ventilation increased in association with an augmentation of the hypercapnic ventilatory response. ACET treatment increased both hypercapnic and hypoxic ventilatory responses. We conclude from the group of patients with COPD studied, that the short-term effects of ACET treatment on gas exchange compare favourably with those of CMA. Oxygen therapy improves oxygenation slightly more than ACET, but aggravates CO2 retention.

Prevalence of naevocytic naevi after chemotherapy for childhood cancer.

The frequency of naevocytic naevi (moles) in patients with childhood haematologic malignancies was studied. All patients had received multiple chemotherapy. The majority had also received cranial irradiation as part of their central nervous system leukaemia/lymphoma prophylaxis. Total body mole counts of the patients were compared with those of their healthy brothers and sisters. The median number of moles in the patient group was 20.0 (n = 79), in the healthy sibs 11.0 (n = 88). In two subgroups mole counts of male and female patients were compared with those of their closet brother or sister. There were 19 male and 19 female pairs for comparison. Median numbers of moles were significantly higher in both patient groups than in the controls (P less than 0.05). It is suggested that multiple chemotherapy (and/or cranial irradiation) may induce or activate naevocytic naevi. These findings may have important implications with regard to the aetiology of melanoma.

Unreliability of self-reported burning tendency and tanning ability.

Burning and tanning histories were studied in 790 white students 18 to 30 years of age by means of a self-administered questionnaire. Only 325 cases (41.1%) were classifiable according to the Fitzpatrick scheme (skin types I to IV). Skin type I (always burn, never tan) was recorded only twice (0.3%). The minimal erythemal dose was measured in a subgroup of 197 students; these results showed no significant correlation with the self-reported burning tendency. In 508 students the burning-tanning histories were compared with eye and hair color, freckling tendency, and number of moles. The tanning ability showed a better correlation with skin complexion characteristics than the burning tendency. It is concluded that self-reported burning-tanning histories form an unreliable means of skin typing.

Prevalence of common "acquired" nevocytic nevi and dysplastic nevi is not related to ultraviolet exposure.

The precise role of ultraviolet radiation in the induction of nevocytic nevi is unsettled. We studied mole counts in relation to the attitude toward ultraviolet exposure in 508 students 18 to 30 years of age. Moles were counted on the chest, back, and legs. Lesions measuring 2 mm or less in diameter and those measuring more than 2 mm were recorded separately. Dysplastic nevi were also recorded separately. The attitude toward sun worship was related to the average periods of sunbathing, the frequency of holidays in sunny climates, and the use of artificial ultraviolet sources. The frequency of pigmented nevi showed no correlation with sun behavior, irrespective of sex, mole size, or burning and tanning propensities. This lack of correlation between ultraviolet exposure and mole counts held true for all solar parameters: periods of sunbathing, sunny holidays, and sunlamp usage. Contrary to expectation, there was a clear, although not statistically significant, excess of dysplastic nevi in subjects with short periods of ultraviolet exposure during leisure. From these data insufficient evidence emerges to support the hypothesis of a correlation between the occurrence of common nevocytic nevi and dysplastic nevi and the degree of insolation by natural or artificial ultraviolet radiation.

Predicting the dynamic effects of rubella vaccination programmes.

In the Netherlands, prepubertal girls have been vaccinated against rubella since 1974 (the UK strategy). Recently the Dutch Health Council advocated the introduction of an elimination strategy: vaccination of 1- and 9-year-old children. Dynamic effects of both strategies are studied using deterministic and stochastic models. Estimates of several epidemiological parameters are given. All computations and simulations were performed using as much field data as possible. Under the old strategy a new equilibrium is expected around the years 1995 to 2000; the new strategy is estimated to eliminate rubella (CRS) in large parts of the population 3 to 5 years after its initiation. Possible consequences of the new strategy on a cluster of people who refuse vaccination are investigated.

Short-term hemodynamic effects of diatrizoate and ioxaglate contrast media in left ventriculography.

Short-term effects in left ventricular performance induced by two contrast media (low osmolar ioxaglate and high osmolar diatrizoate) were evaluated in 24 and 26 patients, respectively. In both groups a diagnosis of valvular heart disease with or without left ventricular disease had been made by noninvasive methods. Changes of hemodynamic data were evaluated in intervals of 20 sec for one min after left ventricular cineangiography. Heart rate increased following injection of both contrast media but was greater with diatrizoate for 20-60 sec (P less than 0.01). A difference in left ventricular systolic pressure was found during 0-60 sec (P less than 0.01), with a decrease in peak left ventricular systolic pressure using diatrizoate (P less than 0.01). In 16 patients without valvular insufficiency, the positive inotropic effect as shown by maximum positive left ventricular pressure slope was more pronounced for diatrizoate during the period of 40-60 sec (P less than 0.05). A decrease in left ventricle relaxation as shown by an increase in the time constant of pressure decay was found for both contrast media. There was no significant difference in relaxation time constant between the two contrast media. During the period of 20-40 sec, the increase in left ventricular end-diastolic pressure was more pronounced for ioxaglate (P less than 0.01) with no untoward consequences in our population of patients.