Differences in circadian blood pressure variability during gestation between healthy and complicated pregnancies

BACKGROUND: Changes in circadian variation of blood pressure (BP) could be used either to predict preeclampsia or to assess its severity. We examined and compared characteristics of circadian variability in BP in women with both healthy and complicated pregnancies who were systematically monitored throughout gestation. METHODS: We analyzed 2430 BP series sampled by ambulatory monitoring for 48 h once every 4 weeks from the first obstetric visit until delivery in 235 women with uncomplicated pregnancies, 128 with gestational hypertension, and 40 with preeclampsia. The circadian pattern of BP variation for each group and trimester of gestation was established by population multiple-components analysis. RESULTS: The differences in 24-h mean and amplitude between healthy and complicated pregnancies were highly significant in all trimesters (P < 0.001). Results further indicated similar circadian characteristics between gestational hypertension and preeclampsia in the first trimester of pregnancy. The difference between these two groups in 24-h mean was statistically significant for systolic (P =.002) and diastolic BP (P =.038) in the second trimester and, to a larger extent, in the third trimester (P < 0.001). CONCLUSIONS: The differences in BP between healthy and complicated pregnancies that can be observed as early as in the first trimester of pregnancy are found when both systolic and diastolic BP for women with a later diagnosis of gestational hypertension or preeclampsia are well within the accepted range of normotension. These differences offer new end points that may lead to an early identification of hypertensive complications in pregnancy as well as to the establishment of prophylactic intervention.     

Prevention of recurrent amiodarone-induced hyperthyroidism by iodine-131

Amioradone-induced hyperthyroidism is a common complication of amiodarone therapy. Although definitive interruption of amiodarone is recommended because of the risks of aggravation of the arrhythmias, some patients may require the reintroduction of amiodarone several months after normalisation of thyroid function. The authors undertook a retrospective study of the effects of preventive treatment of recurrences of amiodarone-induced hyperthyroidism with I131. The indication of amiodarone therapy was recurrent, symptomatic, paroxysmal atrial fibrillation in 13 cases and ventricular tachycardia in 5 cases (M = 14, average age 64 +/- 13 years). The underlying cardiac disease was dilated cardiomyopathy (N = 5), ischaemic heart disease (N = 3), hypertensive heart disease (N = 2), arrhythmogenic right ventricular dysplasia (N = 2) or valvular heart disease (N = 2). Two patients had idiopathic atrial fibrillation. An average dose of 576 +/- 184 MBq of I131 was administered 34 +/- 37 months after an episode of amiodarone-induced hyperthyroidism. Amiodarone was reintroduced in 16 of the 18 patients after a treatment-free period of 98 +/- 262 days. Transient post-radioiodine hyperthyroidism was observed in 3 cases (17%). Sixteen patients (89%) developed hypothyroidism requiring replacement therapy with L-thyroxine. There were no recurrences of amiodarone-induced hyperthyroidism. After 24 +/- 17 months follow-up, the arrhythmias were controlled in 13 of the 16 patients (81%) who underwent the whole treatment sequence. The authors conclude that preventive treatment with I131 is an effective alternative to prevent recurrence of amiodarone-induced hyperthyroidism in patients requiring reintroduction of amiodarone to control their arrhythmias.     

Purified and highly aggregated chimeric protein DIIIC-2 induces a functional immune response in mice against dengue 2 virus

It was previously reported that DIIIC-2 (a fusion protein composed of domain III of the envelope protein and the capsid protein from dengue 2 virus), as an aggregate antigen from a partially purified preparation, induced a functional protective immune response against dengue 2 virus in the mouse encephalitis model. In the present work, a purification procedure was developed for DIIIC-2, and soluble and aggregated fractions of the purified protein were characterized and evaluated in mice. The purification process rendered a protein preparation of 91 % purity, and the remaining 9 % consisted of fragments and aggregates of the same recombinant protein. After the in vitro aggregation process, upon addition of oligodeoxynucleotides, 80 % of the protein formed aggregates, whereas 20 % remained as soluble protein. An immunological evaluation revealed the proper immunogenicity of the aggregated purified protein in terms of induction of antiviral and neutralizing antibodies, cell-mediated immunity and protection upon dengue 2 virus challenge in the mouse encephalitis model. Based on these results, we can assert that the purified protein DIIIC-2 is functional and could be used for further scalable steps and preclinical studies in non-human primates.     

Phenytoin immunoassay measurements in serum samples from patients with renal insufficiency: comparison with high-performance liquid chromatography

The debate continues regarding the possible interference of phenytoin metabolites in phenytoin immunoassays, and its clinical importance for patients with renal failure. The aim of this study was to compare the results obtained using the Abbott fluorescence polarization immunoassay (FPIA), Dade enzyme-multiplied immunoassay technique (EMIT), and high-performance liquid chromatography (HPLC) to establish the significance of the differences in conditions of renal failure. Thirty-six adult patients who had been treated with phenytoin and whose renal function ranged from normal to severely impaired were chosen for this study. In accordance with previously established validation criteria for analytical methods for the determination of drugs, a 15% bias from the HPLC phenytoin values was considered an acceptable limit. The mean (+/-SEM) glomerular filtration rate (GFR) of the patients was 37.5+/-4.6 mL/min (range = 10-102 mL/min).The mean values found using FPIA (10.8+/-1.2 microg/mL) and EMIT (10.8+/-1.3 microg/mL) presented acceptable deviations with respect to HPLC (10.5+/-1.2 microg/mL), and a high correlation was found among the results (N = 36) of the different methods (r > or = 0.987, P < 0.001). An FPIA deviation above the 15% bias limit with respect to HPLC was found only in two cases with very low serum phenytoin concentrations and low GFR values (< 20 mL/min), although it does not appear to be important in terms of adjusting drug dosage. According to our data, FPIA and EMIT gave accurate results for total phenytoin in serum samples from patients with renal failure.     

Comparison of predose vs 2-h postdose blood metabolites/cyclosporine ratios in kidney and liver transplant patients

OBJECTIVES: It has recently been suggested that when adjusting doses of cyclosporine (CsA), determining its concentration in blood samples taken 2 h postdose (C(2)) is more clinically beneficial than using the predose concentration (C(0)). We determined C(0) and C(2) concentrations of CsA and their metabolites in samples taken from nine kidney and seven liver transplant patients. Similarly, the so-called metabolic ratios (MR)-metabolites to CsA parent ratios-were calculated to characterise the most suitable moment of blood sampling for obtaining a greater analytical specificity with monoclonal immunoassays. METHODS: The determination of CsA and CsA + metabolites was made using the enzyme multiplied immunotechnique and the polyclonal fluorescence polarization immunoassay Abbott TDx, respectively. RESULTS: The poor correlation between C(0) and C(2) of CsA (n = 82, r = 0.387, p < 0.001) is greatly inferior to that obtained between C(0) and C(2) of metabolites (n = 82, r = 0.912, p < 0.001). A highly significant difference (p < 0.001) was found between MR(0) values (mean 2.87 +/- 0.12, median 2.48) and MR(2) values (mean 1.73 +/- 0.09, median 1.46), although there is a good correlation between them (r = 0.878, p < 0.001). CONCLUSIONS: The extent of the positive bias (deviation) of CsA immunoassays compared with the high-performance liquid chromatography results is related to the MR values. As the MR(2) values are significantly lower than the corresponding MR(0), in practice a greater analytical specificity would be obtained with the different monoclonal immunoassays in the determination of the 2 h postdose CsA concentration than in that of trough concentration.     

Wear of polyethylene against oxidized zirconium femoral components effect of aggressive kinematic conditions and malalignment in total knee arthroplasty

Metallic femoral components with ceramic articulating surfaces can substantially lower polyethylene (PE) wear during walking activities under conditions of normal knee alignment. It is unknown whether these types of components can maintain low wear rates under conditions of knee malalignment and the harsher kinematics associated with younger, athletically active patients. Wear was measured in non-cross-linked, ethylene oxide-sterilized PE inserts against oxidized zirconium or cobalt-chrome femoral components in a knee wear simulator. The vertical load was modified to replicate knee varus malalignment of 3°, and the range of tibial rotation was increased to 20°. Mean gravimetric and volumetric wear rate over 5 million cycles was 55% lower in the oxidized zirconium group. An oxidized zirconium femoral component can significantly reduce PE wear under simulated conditions of athletically active patients with modestly malaligned total knee arthroplasty prostheses.     

Significance of an upward shift of the ST segment during an exercise test

The objective of this study is to investigate the significance of the occurrence of an upward shift of the ST segment curing a stress test in patients with no previous history of myocardial infarction. Over 10 years, totalling 9,500 stress tests, we have collected 10 cases. They always concern men including one with angina on exertion, one with spontaneous angina, one with spontaneous angina occurring at the end of an intense stress, and 7 with mixed angina. None of them had a previous history of myocardial infarction or documented spastic angina. The upward shift of the ST segment occurred 9 times during stress and once during recovery. 9 patients had a coronary arteriogram with in 8 cases severe fixed coronary lesions. The patient with the upward shift of ST during the recovery period had a normal coronary arteriogram with a positive methylergometrin test. There is a good correlation between the appearance of an upward shift of ST during stress in the anterior derivations and a significant involvement of the anterior interventricular artery. In our series, there were no complications, especially myocardial infarction, in the immediate period following the stress test. 7 patients underwent an aorto-coronary by-pass. The 10 patients are presently asymptomatic after a 47 months follow-up. The occurrence of an upward shift of ST during stress, in the absence of a previous history of myocardial infarction, represents in more than 80 p. cent of the cases the existence of severe coronary lesions leading to hospitalization and the immediate performance of a coronary arteriogram.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reference thresholds for 24-h, diurnal, and nocturnal ambulatory blood pressure mean values in pregnancy

OBJECTIVES: Several studies have indicated that the use of the 24-h mean of blood pressure, mainly using reference thresholds derived from the general non-pregnancy practice, does not provide a proper test for diagnosis of hypertension in pregnancy. This prospective study examines previously derived reference thresholds for the 24-h, diurnal, and nocturnal mean of blood pressure as potential screening tests for the diagnosis of hypertension in pregnancy. METHODS: We studied 235 normotensive and 168 hypertensive pregnant women, who provided 2430 blood pressure series sampled every 20 min during the day and every 30 min at night for 48 consecutive hours once every 4 weeks from the first obstetric visit until delivery. Sensitivity and specificity for each parameter are based on the comparison of the distributions of mean blood pressure values with reference thresholds previously established from an independent population of 113 pregnant women also evaluated monthly by 48-h ambulatory monitoring throughout gestation. RESULTS: Sensitivity of mean blood pressure values, above 70% at all stages of pregnancy, was higher than that obtained from clinic blood pressure measurements, which were always below 14%. The poorest results were consistently obtained for the nocturnal mean. Sensitivity was similar for the 24-h and the diurnal mean, with values ranging from 71% for diastolic blood pressure in the first trimester of pregnancy to 93% for systolic blood pressure in the third trimester. Systolic blood pressure consistently provided better sensitivity than diastolic blood pressure at all gestational ages. CONCLUSIONS: This prospective study on women systematically studied by 48-h ambulatory monitoring throughout gestation indicates that mean ambulatory blood pressure values provide higher sensitivity and specificity than conventional measurements. Moreover, results indicate that diagnosis of hypertension in pregnancy based on ambulatory blood pressure should be established from thresholds much lower than those currently used in clinical practice.